Song Jing-Chun, Guo Jun, Zhang Lei, Ding Ren-Yu, Wang Gang, Zhang Wei, Zhou Jing, Ke Lu, Zhang Jin-Hua, Chinese Society of Thrombosis, Hemostasis and Critical
摘要:Over 40% of critically ill patients will develop coagulopathy. Once critically ill patients are complicated with coagulopathy, the incidence of bleeding and mortality can increase by more than 4 times. Early identification of coagulopathy and accurate evaluation of coagulation function are essential for correcting coagulopathy as soon as possible. Therefore, Chinese Society of Thrombosis, Hemostasis and Critical Care, Chinese Medicine Education Association, together with Chinese People's Liberation Army Professional Committee of Critical Care Medicine updated the "Chinese expert consensus on standardized assessment of severe coagulopathy (2025 Edition)" on the basis of the "Consensus of Chinese experts on standardized evaluation of coagulation dysfunction in severe patients" formulated in 2022. This consensus includes four parts: classification and typing, etiology and mechanism, assessment methods, and diagnostic criteria of severe coagulopathy, with a total of 14 recommendations, aiming to provide corresponding guidance for clinical practice.
摘要:Chikungunya fever (CHIKF) is a mosquito-borne infectious disease caused by Chikungunya virus (CHIKV) infection, which has become a significant public health threat of global concern in recent years. The acute phase of CHIKF is primarily characterized by sudden high fever, severe polyarthralgia, and rash. The disabling arthralgia may progress to chronic arthritis, with symptoms lasting for months or even years. This not only severely reduces patients' quality of life and impairs their labor capacity, but also imposes a heavy socioeconomic burden. In recent years, significant progress has been made in CHIKF-related research. This review elaborates on the latest research achievements in the fields of the disease's epidemiology, clinical manifestations, pathogenic mechanisms, immune response, diagnostic techniques, and prevention and treatment strategies, aiming to provide comprehensive and in-depth references for researchers and clinicians in relevant fields.
摘要:ObjectiveTo investigate the characteristics of changes in hepatitis B surface antigen (HBsAg), hepatitis B virus (HBV) deoxyribonucleic acid (DNA), and alanine aminotransferase (ALT) levels following the cessation of nucleos(t)ide analogues(NAs) therapy in hepatitis B e antigen (HBeAg)-negative chronic hepatitis B (CHB) patients with baseline HBsAg levels <1000 IU/ml.MethodsThis retrospective cohort study analyzed 73 HBeAg-negative CHB patients treated at the Fifth Medical Centre of Chinese PLA General Hospital from January 2020 to June 2023. Patients were divided into 3 groups according to baseline HBsAg level and discontinuation strategy: HBsAg-negative discontinuation group (n=14), HBsAg-positive discontinuation group (n=25), and HBsAg-positive continuation group (n=34). All patients were followed for 48 weeks. Baseline clinical characteristics and changes in virological and hepatic biochemical indicators during follow-up were compared among the 3 groups. Univariate logistic regression analysis was performed to assess the correlation between clinical indicators and HBV DNA reappearance in HBsAg-positive discontinuation group, and between clinical indicators and HBsAg decline >0.5 log IU/ml in this group.ResultsThere were no significant differences in the baseline levels of gender, age, albumin, and total bilirubin among the 3 groups (P>0.05). The baseline direct bilirubin level was significantly higher in HBsAg-positive discontinuation group than that in other groups (P<0.05), while the lymphocyte counts were significantly higher in HBsAg-negative discontinuation group (P<0.05). During the 48-week follow-up period, the HBV DNA reappearance rate in HBsAg-positive discontinuation group (72.0%) was significantly higher than that in other groups (P<0.001). There was no significant difference in the incidence of ALT elevation among the three groups (P=0.260). The proportion of patients with HBsAg decline >0.5 log IU/ml in HBsAg-positive discontinuation group (24.0%) was significantly higher than that in HBsAg-positive continuation group (5.9%, P<0.05). The proportion of patients with HBsAg increase >0.5 log IU/ml in HBsAg-positive discontinuation group (12.0%) was also significantly higher than that in HBsAg-positive continuation group (0%, P<0.05). Univariate logistic regression analysis revealed no significant association between the analyzed clinical indicators and HBsAg decline (P>0.05).ConclusionsDiscontinuation of NAs therapy in HBsAg-negative patients demonstrates high safety, with sustained HBsAg negativity post-cessation and low risks of viral relapse and liver function abnormalities. For HBsAg-positive patients, discontinuation may promote HBsAg decline in some individuals but is associated with risks of HBV DNA reappearance and HBsAg elevation. The decision to discontinue therapy should be comprehensively evaluated based on patients' baseline HBsAg levels and clinical characteristics.
摘要:ObjectiveTo investigate the correlation of corneal α angle and κ angle with lens tilt in normal human eyes using a new swept-source optical biometer.MethodsA cross-sectional study was conducted, involving 303 healthy eyes (148 right eyes and 155 left eyes) of patients who visited the First Affiliated Hospital of Kunming Medical University from June to August 2024. ZW-30 swept-source optical biometer was used to collect the lens tilt angle, κ angle (distance from the corneal light reflex to the pupil center), and α angle (distance from corneal light reflex to the corneal geometric center, which is the midpoint of the horizontal white to white (WTW) diameter). The degrees (°) and directions of κ angle and α angle were calculated by the ratio of the above measurements to the anterior chamber depth (ACD) respectively. Spearman correlation analysis and linear regression analysis were employed to evaluate the correlations between the magnitude and direction of corneal α angle, κ angle and lens tilt angle.ResultsThe magnitude and direction of corneal α angle, κ angle, and lens tilt angle in the right eye were as follows respectively: (0.54±0.19) mm (7.81°±3.88°), 194.43°±39.75°; (0.27±0.23) mm (4.72°±3.90°), 181.07°±79.59°; 5.52°±1.67°, 188.21°±25.73°. For the left eye, the corresponding values were: (0.47±0.27) mm (8.12°±5.26°), 336.04°±46.64°; (0.26±0.27) mm (4.45°±4.80°), 322.86°±107.79°; 5.50°±1.61°,340.65°±32.84°. Spearman's correlation analysis showed that the correlation coefficients between corneal α angle and lens tilt angle in the right eye were 0.609 (distance correlation) and 0.625 (angle correlation), while those for κ angle were 0.559 (distance correlation) and 0.578 (angle correlation). In the left eye, the correlation coefficients between corneal α angle and lens tilt angle were 0.545 (distance correlation) and 0.552 (angle correlation), and those for κ angle were 0.377 (distance correlation) and 0.395 (angle correlation). In addition, the correlation coefficient between the direction of corneal α angle and the direction of lens tilt angle in the right eye was 0.343, and that for κ angle direction was 0.284; in the left eye, the correlation coefficients were 0.216 (α angle direction) and 0.198 (κ angle direction), all with statistical significance (P<0.05). Univariate linear regression analysis showed that lens tilt was positively correlated with both corneal α angle and Kappa angle (P<0.05).ConclusionsCorneal α angle and κ angle are highly correlated with lens tilt angle in both eyes, and the correlation of corneal α angle is stronger than that of κ angle in both left and right eyes. The correlation expressed by degree (°) is better than that by distance (mm). It is recommended to refer to the corneal α angle and κ angle expressed in degrees during preoperative evaluation.
摘要:ObjectiveTo investigate the association between high-density lipoprotein cholesterol (HDL-C) levels and all-cause and cause-specific mortality in the elderly population, and to determine the optimal HDL-C concentration range associated with the lowest mortality risk.MethodsThis prospective cohort study included 16,632 elderly individuals aged ≥60 years from the National Health and Nutrition Examination Survey (NHANES) between 1999 and 2018. Participants were divided into 5 groups based on HDL-C levels: <40 mg/dl group (n=2933), 40-49 mg/dl group (n=4602), 50-59 mg/dl group (n=3824), 60-79 mg/dl group (n=3988), and ≥80 mg/dl group (n=1285). Mortality data were obtained by linking records with the National Death Index (NDI). Cox proportional hazards regression and restricted cubic spline curves were used to analyze the association between HDL-C and mortality risk. Subgroup and sensitivity analyses were conducted.ResultsMultivariable-adjusted Cox models showed that, compared with 50-59 mg/dl HDL-C group, HDL-C<40 mg/dl group had significantly higher risks of all-cause mortality (HR=1.17, 95%CI 1.05-1.31, P=0.006), cardiovascular mortality (HR=1.32, 95%CI 1.08-1.58, P=0.001), and non-cardiovascular mortality (HR=1.14, 95%CI 1.02-1.27, P=0.013). HDL-C≥80 mg/dl group had significantly higher risks of all-cause mortality (HR=1.18, 95%CI 1.03-1.35, P=0.027) and non-cardiovascular mortality (HR=1.23, 95%CI 1.03-1.46, P=0.029), but no significant effect on cardiovascular mortality (HR=1.07, 95%CI 0.88-1.28, P=0.492). Restricted cubic spline curves revealed U-shaped associations between HDL-C and all-cause/non-cardiovascular mortality, and an inverse J-shaped association with cardiovascular mortality. These patterns were consistent in both elderly men and women. The HDL-C levels associated with the lowest risk were 56 mg/dl (95%CI 53-59 mg/dl) for all-cause mortality, 54 mg/dl (95%CI 51-57 mg/dl) for cardiovascular mortality, and 59 mg/dl (95%CI 56-62 mg/dl) for non-cardiovascular mortality. Subgroup analyses showed no significant effect modifications. Sensitivity analyses confirmed the primary findings.ConclusionsIn the elderly population, extremely high HDL-C levels increase the risks of all-cause mortality and non-cardiovascular mortality, but do not elevate cardiovascular mortality. The risk of all-cause mortality is the lowest at an HDL-C concentration of 56 mg/dl.
摘要:ObjectiveTo investigate the epidemiological characteristics of Mycoplasma pneumoniae (MP) infection among pediatric inpatients with respiratory tract infections (RTIs) at Children's Hospital of Hebei Province, providing evidence for clinical diagnosis and treatment.MethodsA retrospective analysis was conducted on 79 546 children hospitalized for RTIs between January 2016 and February 2024. Nasopharyngeal aspirates or deep sputum samples were collected, and polymerase chain reaction (PCR) was used to detect nucleic acids of 13 respiratory pathogens, including MP and adenovirus. The epidemiological trends across different years, seasons, genders, and age groups were analyzed.ResultsAmong the 79 546 enrolled cases (male: 47 437, 59.6%; female: 32 109, 40.4%), the MP-positive rate was 17.7% (14 106/79 546), peaking in 2023 (28.8%) and reaching the lowest in 2021 (7.0%). Except for the period from July 2020 to March 2021 with exceptionally low MP positivity, epidemic peaks consistently occurred between August and February or March of the following year. Seasonal analysis revealed significantly higher MP positivity in autumn and winter compared to spring (P<0.001). Female children exhibited a higher MP-positive rate (20.1%, 6444/32 109) than males (16.2%, 7662/47 437) (P<0.001). The MP-positive rate increased with age: infancy (3.2%, 849/26 741), toddlerhood (9.3%, 1935/20 763), preschool (21.2%, 3918/18 448), and school-age (54.5%, 7404/13 594) (P<0.001). Co-infections with other respiratory pathogens were observed in 37.3% (5264/14 106) of MP-positive cases, with human rhinovirus (HRV) being the most frequent co-pathogen (43.3%, 2279/5264 of mixed infections).ConclusionMP is a major pathogen of RTIs in hospitalized children at Children's Hospital of Hebei Province. Infections occur year-round but predominantly in autumn, with higher susceptibility in females and school-age children. Targeted preventive measures should be implemented during peak seasons to mitigate transmission risks.
摘要:ObjectiveTo analyze the clinical characteristics, treatment, and prognosis of immune checkpoint inhibitor-related diabetes mellitus (ICI-DM).9 cases (90.0%) had a severity of adverse events reaching grade 3-4 according to the Common Terminology Criteria for adverse events (CTCAE). The median time from PD-1 inhibitor treatment to the occurrence of the classic diabetes symptoms referred to as "three more and one less" (polyuria, polydipsia, polyphagia, and weight loss) in all patients was 145.5(110.5, 204.8) days, and the medication duration was 6.0 (4.3, 7.8) cycles. The average blood glucose level of the 10 patients at the time of consultation was 25.3 (10.0-41.4) mmol/L, and the glycated hemoglobin (HbA1c) level was 8.0% (6.6%-10.9%). Eight patients had fasting and 2-hourMethodsThe clinical characteristics, laboratory examinations, treatment regimens, and follow-up outcomes of 10 ICI-DM patients who were diagnosed and treated in the First Medical Center of Chinese PLA General Hospital between July 2019 and December 2024 were retrospectively analyzed. Relevant literatures were retrieved from domestic and foreign databases such as PubMed, CNKI, and VIP. The clinical characteristics of ICI-DM were summarized based on the literature results.ResultsAll 10 patients were PD-1 inhibitor users, including 5 males and 5 females, with a median age of 54.5 (51.3, 64.0) years and a body mass index (BMI) of (22.0±2.15) kg/m². Among them, 9 cases (90.0%) were fulminant type 1 diabetes mellitus (FT1DM);C-peptide levels <0.1 ng/ml (fasting C-peptide from <0.010 to 0.067 ng/ml, 2-hour C-peptide from <0.010 to 0.077 ng/ml). Nine of the 10 patients were negative for diabetes autoantibodies, while 1 was not tested. All 10 patients were successfully treated with insulin and other therapies. During the follow-up after discharge, all patients still relied on insulin treatment, and no significant recovery of pancreatic islet β cell function was observed compared with that at discharge. Literature review revealed that ICI-DM was more common in PD-1 inhibitor users, with clinical mainly manifested as diabetic ketoacidosis (DKA) (65.4%) and diabetic ketosis (13.1%). Patients had severely impaired pancreatic islet function and required long-term insulin treatment, and some cases were complicated by thyroid or pituitary dysfunction.ConclusionsICI-DM typically presents as FT1DM, often manifesting with DKA or diabetic ketosis at onset. It is characterized by severe and irreversible loss of pancreatic islet function, necessitating lifelong insulin therapy. To enable early detection and prompt treatment, close monitoring of blood glucose is essential during ICI treatment.
摘要:ObjectiveTo identify risk factors for severe hand-foot-mouth disease (HFMD) cases in Fuzhou, providing scientific evidence for disease prevention and control.MethodsSevere pediatric HFMD cases in Fuzhou between 2017 and 2024 were collected from the "China Disease Prevention and Control Information System". Non-severe cases were frequency-matched based on the same onset period, same affected region, same parents' educational level, and age (±1 year) to form a non-severe group. Demographic characteristics, clinical symptoms, medical history, and pathogen types of both groups were collected. Logistic regression was used to identify the risk factors for severe cases.ResultsFrom 2017 to 2024, Fuzhou reported 503 severe HFMD cases and 1053 matched non-severe cases. Demographically, severe group had a higher proportion of home-based childcare, rural residence, care-seeking delay >2 d, while EV71 vaccination rates, handwashing habits before meals and after defecation, and caregivers with HFMD prevention education were lower than those in non-severe group, with statistically significant difference (P<0.001). Clinically, severe group showed more frequent fever >3 d, altered consciousness/seizure, limb tremors/convulsions, the proportion of infectious disease and the proportion of EV71-positive cases than those in non-severe group (P<0.001). Multivariate logistic regression analysis showed that home-based childcare (OR=3.213, 95%CI 1.913-5.398), rural residence (OR=2.121, 95%CI 1.513-2.973), lack of EV7 vaccination (OR=3.141, 95%CI 1.996-4.945),care-seeking delay >2 d (OR=2.004, 95%CI 1.410-2.849), no handwashing habits before meals and after defecation (OR=3.927, 95%CI 1.718-5.356), caregiver without HFMD education (OR=2.465, 95%CI 1.807-3.362), fever >3 d (OR=2.585, 95%CI 1.801-3.709), altered consciousness/seizures (OR=4.059, 95%CI 2.731-6.031), limb tremors/convulsions (OR=2.087, 95%CI 1.398-3.117), history of infectious disease (OR=3.369, 95%CI 1.725-6.335) and EV71 positivity (OR=3.854, 95%CI 2.678-5.545) were risk factors for severe HFMD cases. The recovery time in severe group was significantly longer than that in non-severe group [18(5, 32) d vs. 11(4, 23) d, P<0.001].ConclusionsPrevention and control efforts should target high-risk groups by strengthening health education, promoting EV71 vaccination and improving the treatment of severe HFMD cases to reduce the incidence of severe HFMD.
摘要:ObjectiveTo analyze the characteristics and risk factors associated with postoperative deep vein thrombosis (DVT) of the lower extremities in patients undergoing surgery for lumbar degenerative diseases.MethodsA retrospective analysis was conducted on clinical data from 298 patients who were hospitalized for lumbar degenerative diseases and underwent lumbar spine surgery treatment in the First Affiliated Hospital of Nanchang University from October 1, 2022 to April 15, 2023. Patients were divided into DVT group (n=71) and non-DVT group (n=227) according to whether DVT of the lower limbs occurred within 1 week postoperatively. The incidence and distribution characteristics of postoperative DVT were analyzed. Univariate and binary logistic regression analyses were performed to identify risk factors for DVT, and receiver operating characteristic (ROC) curves were used to determine cut-off values for relevant risk factors.ResultsA total of 298 patients were included, among whom 159 were males (53.4%) and 139 were females (46.6%), with an average age of (64.5±9.8) years. DVT occurred in 71 patients, and the incidence of lower extremity DVT was 23.8%. In the DVT group, there were 49 cases (69.0%) of intermuscular vein thrombosis, and 22 cases of other types of thrombosis (7 cases of peroneal vein thrombosis, 4 cases of posterior tibial vein thrombosis, 3 cases of common femoral vein thrombosis, 1 case of anterior tibial vein thrombosis, and 7 cases of multiple thrombosis); 58 cases (81.7%) had DVT in one lower extremity, and 13 cases (18.3%) had DVT in both lower extremities. Univariate analysis results showed that age, body mass index (BMI), length of hospital stay, history of hypertension, operative time, and intraoperative blood loss were associated with the occurrence of lower extremity DVT after surgery for lumbar degenerative diseases (P<0.05). Binary logistic regression analysis results indicated that older age (OR=1.079, P<0.01), higher BMI (OR=1.130, P=0.01), history of hypertension (OR=2.992, P<0.01), and larger intraoperative blood loss (OR=1.002, P=0.03) were independent risk factors for the occurrence of lower extremity DVT. ROC curve analysis demonstrated that patients with age>58.5 years, BMI>24.01 kg/m², history of hypertension, and intraoperative blood loss >550 ml had a significantly increased risk of postoperative lower limb DVT.ConclusionsThe incidence of lower extremity DVT after surgery for lumbar degenerative disease is high, and intermuscular venous thrombosis is more common. Older age, higher BMI, history of hypertension, and larger intraoperative blood loss are independent risk factors for the occurrence of lower extremity DVT after surgery.
关键词:lumbar degenerative diseases;lower extremity deep vein thrombosis;risk factors;postoperative complications
摘要:ObjectiveTo investigate the postoperative efficacy of laparoscopic hiatal hernia repair (LHHR) combined with Toupet or Dor fundoplication for the treatment of esophageal hiatal hernia (HH).MethodsA retrospective analysis was conducted on the case data of HH patients who underwent LHHR combined with Toupet (Toupet group, n=53) and Dor (Dor group, n=53) fundoplication between December 2018 and December 2022 in Department of General Surgery of Gansu Provincial Hospital. Intraoperative and postoperative recovery outcomes of both groups were observed. We analyzed and compared the incidence of dysphagia and gastroesophageal reflux disease questionnaire (GERD-Q) scores at preoperative and postoperative intervals of 1 month, 6 months, and 1 year. The incidence of postoperative complications and the 1-year recurrence rate were compared between the two groups. Additionally, factors influencing postoperative dysphagia within the first month were examined.ResultsThe differences between the two groups in operation time, intraoperative bleeding, postoperative ventilation time, postoperative extubation time and hospitalization time were not statistically significant (P>0.05). There was no significant difference in the incidence of immediate postoperative dysphagia in two groups (P>0.05). Furthermore, the differences between the two groups in the incidence of postoperative complications, such as bloating, abdominal pain and diarrhea, were not statistically significant (P>0.05). The incidence of dysphagia in Toupet group was higher than that in Dor group at 1 month postoperatively, and the difference was statistically significant (P=0.017); but the difference in the incidence of dysphagia between the two groups at 6 months and 1 year postoperatively was not statistically significant (P=0.767, 1.000). The results of binary logistic regression analysis showed that both surgical procedure (OR=2.613, 95%CI 1.141-5.983, P=0.023) and esophageal contractile reserve function (OR=2.921, 95%CI 1.203-7.095, P=0.018) were independent risk factors for the incidence of dysphagia in patients with HH at 1 month after surgery. Compared with the preoperative period, the GERD-Q symptom scores were lower in both groups at 1 month, 6 months, and 1 year postoperatively, and the difference was statistically significant (P<0.05); but there was no statistically significant difference between the groups at the same time point (Fintergroup=0.334, P=0.565). The difference between the two groups in 1-year postoperative recurrence rates was not statistically significant (P>0.05).ConclusionsLHHR combined with Toupet or Dor fundoplication are both safe and effective surgical procedures for the treatment of HH, with excellent reflux control, fewer complications and lower recurrence rates, but Toupet fundoplication is more likely to have postoperative short-term dysphagia than Dor fundoplication.
摘要:ObjectiveTo investigate the factors influencing pathologic complete response (pCR) after neoadjuvant chemotherapy (NAC) and its correlation with prognosis in patients with human epidermal growth factor receptor 2 (HER2)-low breast cancer.MethodsA retrospective analysis was conducted on patients with HER2-low breast cancer who underwent NAC at the Second Affiliated Hospital of Jiujiang College from February 28, 2018 to February 28, 2021. Patients were divided into pCR group (achieved pCR, n=143) and non-pCR group (did not achieve pCR, n=300) based on pCR status. General clinicopathological data were collected and compared between the two groups, including age, surgical method, NAC regimen, postoperative radiotherapy, clinical tumor stage, tumor cT stage, tumor cN stage, pathological type, tumor Nottingham grade, hormone receptor (HR) status, Ki-67 status, menopausal status, and endocrine therapy. Binary logistic regression analysis was used to identify factors influencing pCR after NAC. Propensity score matching (1:1) was employed to balance baseline characteristics between the two groups. The matched groups' baseline data were compared. Kaplan-Meier method was used for survival analysis of the matched cohorts. Multivariate Cox proportional hazards regression models were used to analyze the independent influence of pCR on disease-free survival (DFS) and overall survival (OS) in HER2-low breast cancer after matching.ResultsA total of 443 patients with HER2-low breast cancer receiving NAC were included, with a mean age of (49.5±8.0) years. Binary logistic regression analysis identified clinical tumor stage (OR=0.498, 95%CI 0.267-0.930), HR status (OR=0.513, 95%CI 0.328-0.801), Ki-67 status (OR=2.580, 95%CI 1.366-4.874), tumor Nottingham grade Ⅲ (OR=3.197, 95%CI 1.147-8.910), and endocrine therapy (OR=0.513, 95%CI 0.328-0.801) as independent factors influencing pCR after NAC (P<0.05). After propensity score matching, 80 patients remained in each group (PCR and non-PCR). No significant differences were found in clinicopathological characteristics between the matched groups (P>0.05). The median follow-up time was 45.0 months (95%CI 43.1-46.9) for pCR group and 43.0 months (95%CI 41.0-45.0) for non-pCR group. The DFS rate was significantly higher in pCR group than that in non-pCR group (87.5% vs. 70.0%, P=0.004), but there was no significant difference in OS rate (88.8% vs. 85.0%, P=0.438). Multivariate Cox regression analysis showed that pCR was an independent factor influencing on DFS (HR=0.312, 95%CI 0.142-0.688, P=0.004), but not OS in HER2-low breast cancer patients.ConclusionsPatients with HER2-low breast cancer who have a lower clinical tumor stage, HR-negative status, high Ki-67 expression, high tumor Nottingham grade, and absence of endocrine therapy are more likely to achieve pCR. Achieving pCR prolongs DFS significantly but does not significantly improve OS in these patients.
关键词:HER2-low breast cancer;neoadjuvant chemotherapy;pathological complete response;disease-free survival;overall survival
摘要:ObjectiveTo investigate plasma protein expression changes in heatstroke patients using proteomics technology and to identify reliable prognostic biomarkers.MethodsA retrospective analysis was conducted on 20 heatstroke patients hospitalized at the 908th Hospital of the Chinese PLA Joint Logistics Support Force from July 2022 to February 2024. Patients were divided into survival (n=16) and death groups (n=4) based on 28-day outcomes. Fasting venous blood samples were collected from both groups for proteomic analysis. Liquid chromatography-mass spectrometry (LC-MS/MS) was used to identify and screen differentially expressed proteins. Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) enrichment analyses were performed. LASSO regression was applied to screen key prognostic biomarkers, and receiver operating characteristic (ROC) curve analysis was used to evaluate their predictive value.ResultsA total of 27 upregulated and 90 downregulated proteins were identified between the two groups. These proteins were primarily involved in biological processes such as immune responses, complement activation, and metabolic processes. LASSO regression analysis indicated that actin-related protein 2 (ARP2), cysteine-rich scavenger receptor type 1 M130 (CD163), and catalase (CAT) could serve as effective biomarkers for evaluating heatstroke prognosis. ROC curve analysis demonstrated that ARP2 had higher diagnostic efficacy (AUC=0.98, sensitivity=0.80, specificity=1.00) compared to CD163 (AUC=0.94, sensitivity=0.76, specificity=1.00), CAT (AUC=0.96, sensitivity=0.67, specificity=1.00), and acute physiology and chronic health evaluation Ⅱ (APACHE Ⅱ) score (AUC=0.79, sensitivity=0.44, specificity=1.00).ConclusionElevated plasma ARP2 level has good clinical value for predicting poor prognosis in heatstroke patients.
摘要:ObjectiveTo investigate the regulatory effect and molecular mechanism of circ_0044556 on the malignant biological behavior of triple negative breast cancer (TNBC) cells by targeting the miR-338-3p/bromodomain-containing protein 4 (BRD4) axis.MethodsThe TargetScan online website was used to predict the binding sites of circ_0044556 with miR-338-3p and miR-338-3p with BRD4. Dual-luciferase reporter gene assays were performed to determine the relationship among circ_0044556, miR-338-3p, and BRD4 in MDA-MB-231 cells. Quantitative real-time PCR (qRT-PCR) and Western blotting were employed to detect the expression of circ_0044556, miR-338-3p, and BRD4 protein in human TNBC cell line MDA-MB-231 and human normal breast epithelial cells MCF-10A. MDA-MB-231 cells were divided into NC group, si-NC group (transfected with si-NC), si-circ_0044556 group (transfected with si-circ_0044556), si-circ_0044556+inhibitor NC group (transfected with si-circ_0044556 and inhibitor NC), and si-circ_0044556+miR-338-3p inhibitor group (transfected with si-circ_0044556 andmiR-338-3p inhibitor). qRT-PCR was applied to detect the expression of circ_0044556 and miR-338-3p; Western blotting was used to detect the expression of BRD4, E-cadherin, N-cadherin and Vimentin; the CCK-8 assay was applied to detect cell proliferation; flow cytometry was applied to detect cell apoptosis; and Transwell assays were used to detect cell invasion and migration. Thirty nude mice were randomly divided into NC group (tail vein injection of normal saline), si-NC group (tail vein injection of LV-NC), si-circ_0044556 group (tail vein injection of LV-circ_0044556), si-circ_0044556+inhibitor NC group (tail vein injection of LV-circ_0044556 and antiagomir NC), and si-circ_0044556+miR-338-3p inhibitor group (tail vein injection of LV-circ_0044556 and antiagomir miR-338-3p), with 6 mice per group. A xenograft tumor model was constructed by subcutaneous injection of MDA-MB-231 cells into nude mice, and tumor volume and weight were measured.ResultsTargetScan prediction results showed that the downstream miRNA of circ_0044556 was miR-338-3p, and the downstream target gene of miR-338-3p might be BRD4. Compared with transfecting mimic NC, transfection with miR-338-3p mimic significantly reduced the luciferase activities of WT-circ_0044556 (0.34±0.03 vs. 1.00±0.15, P<0.05) and WT-BRD4 (0.41±0.05 vs. 1.05±0.13, P<0.05) in MDA-MB-231 cells. Compared with MCF-10A cells, the expression levels of circ_0044556 and BRD4 protein in MDA-MB-231 cells were significantly increased, while the expression level of miR-338-3p was significantly decreased (P<0.05). Compared with NC group and si-NC group, the expression levels of circ_0044556, the protein expression levels of BRD4, N-cadherin, and Vimentin, and the OD450 value in MDA-MB-231 cells of si-circ_0044556 group and si-circ_0044556+inhibitor NC group were significantly decreased (P<0.05), the number of migrated and invaded cells was significantly reduced (P<0.05), and the expression level of miR-338-3p, the protein expression level of E-cadherin, and the cell apoptosis rate in MDA-MB-231 cells were significantly increased (P<0.05); downregulation of miR-338-3p rescued the inhibitory effect of circ_0044556 knockdown on invasion, migration, and proliferation of MDA-MB-231 cells. Compared with NC group and si-NC group, the tumor volume and weight in si-circ_0044556 group and si-circ_0044556+inhibitor NC group were significantly decreased (P<0.05); compared with si-circ_0044556 group and si-circ_0044556+inhibitor NC group, the tumor volume and weight in si-circ_0044556+miR-338-3p inhibitor group were significantly increased (P<0.05).Conclusioncirc_0044556 may promote the malignant biological behaviors of TNBC cells through the miR-338-3p/BRD4 axis.
关键词:circ_0044556;miR-338-3p;bromodomain-containing protein 4;triple negative breast cancer;proliferation;migration;invasion
Wang Chuang-Ye, Wang Ran, Zhang Jian, Qiu Ling-Xiao, Qing Bin, You Heng, Liu Jin-Cheng, Wang Bin, Wang Nan-Bo, Li Jia-Yu, Liu Xing, Wang Shuang, Hu Jin, Wen Jian, Li Quan, Huang Xiao-Ou, Zhao Kun, Liu Shuang-Lin, Liu Gang, Wang Mei-Ju, Xiang Qing, Wu Hong-Mei, Sun Xiao-Rong, Gu Tao, Zhang Dong, Li Qi, Xu Zhi
摘要:ObjectiveTo establish a stable, reliable, and clinically relevant porcine model of endotoxin-induced acute respiratory distress syndrome (ARDS).MethodsTen 8-month-old male Bama minipigs were deeply sedated, followed by invasive mechanical ventilation and electrocardiographic monitoring. Lipopolysaccharide (LPS) was intravenously pumped at 600 μg/(kg·h) for 3 hours, then maintained at 15 μg/(kg·h) thereafter. Dynamic monitoring was performed at five time points after LPS injection (LPS 0, 1, 3, 5, and 8 h), including arterial blood gas analysis and chest computed tomography (CT) scans. Pathological examination of lung tissues obtained via bronchoscopic biopsy (HE staining and transmission electron microscopy) was conducted. These indicators were comprehensively used to evaluate the success of the animal model.ResultsAt 5 hours after LPS administration,8 minipigs developed symptoms such as skin cyanosis, elevated body temperature, and respiratory distress. The oxygenation index decreased to <300 mmHg. Chest CT scans showed diffuse pulmonary infiltrates. Histopathology revealed alveolar edema and hyaline membrane formation. Transmission electron microscopy demonstrated disruption of pulmonary blood-air barrier, depletion of lamellar bodies in type Ⅱ pneumocytes, inflammatory cell infiltration, and exudation of plasma proteins and fibrin. Compared with LPS 0 h, at LPS 8 h, the oxygenation index and arterial blood pH were significantly decreased (P<0.001), while blood lactic acid and serum potassium were significantly increased (P<0.05); serum calcium and base excess were significantly decreased (P<0.05), and the lung injury score based on HE-stained lung sections was significantly increased (P<0.01).ConclusionThe porcine ARDS model established by continuous LPS injection can dynamically simulate the pathophysiological characteristics and typical pathological manifestations of clinical septic ARDS, making it an effective tool to study the pathogenesis, prevention, and treatment strategies of septic ARDS.
摘要:ObjectiveTo investigate the effects and mechanisms of ubiquitin-associated domain-containing protein 2 (UBAC2) mediated by m6A methylation modification on the invasion and migration abilities of colorectal cancer cells.MethodsThe GEPIA2.0 database was utilized to analyze the expression differences of UBAC2 mRNA between colorectal cancer tissues and adjacent normal tissues, as well as its expression in colorectal cancer tissues at different stages. The correlation between Wilms tumor 1-associated protein (WTAP) and UBAC2 expression was analyzed. The Kaplan-Meier plotter online tool was applied to analyze the correlation between UBAC2 and the overall survival rate of colorectal cancer patients. The RMVar and SRAMP databases were employed to predict potential m6A methylation modification sites in the UBAC2 gene. Quantitative real-time PCR (qRT-PCR) and Western blotting were performed to detect the expression levels of UBAC2 mRNA and protein in colorectal cancer cell lines. For UBAC2 knockdown experiments, SW480 cells were divided into control group (no treatment), sh-NC group (transfected with sh-NC negative control plasmid), and sh-UBAC2 group (transfected with sh-UBAC2 plasmid). For WTAP knockdown experiments, groups included control group (no treatment), si-NC group (transfected with negative control siRNA), and si-WTAP group (transfected with WTAP-targeting siRNA). For UBAC2 overexpression experiments, groups were control group (no treatment), si-WTAP group (transfected with pcDNA3.1 empty plasmid), and si-WTAP+OE-UBAC2 group (transfected with UBAC2 overexpression plasmid pcDNA3.1-UBAC2). Western blotting was used to detect the protein expression levels of UBAC2, WTAP, E-cadherin, N-cadherin, and Vimentin; qRT-PCR was applied to detect the expression level of UBAC2 mRNA; Transwell assays were conducted to assess cell invasion and migration abilities. MeRIP-qPCR was employed to detect the m6A methylation modification of UBAC2 mRNA; RIP-qPCR experiments were conducted to verify the binding of WTAP to UBAC2 mRNA. In nude mouse colorectal cancer lung metastasis experiments, groups included LV-sh-NC group (tail vein injection of SW480 cells stably infected with LV-sh-NC) and LV-sh-UBAC2 group (tail vein injection of SW480 cells stably infected with LV-sh-UBAC2). After 42 d of tumor-implantation in nude mice, lung tissues were harvested: the number of lung nodules observed by hematoxylin/eosin (HE) staining, and the expression level of Luc2 mRNA detected by qRT-PCR.ResultsGEPIA2.0 database analysis revealed that the expression level of UBAC2 mRNA in colorectal cancer tissues was significantly higher than that in adjacent normal tissues, and it gradually increased with the progression of tumor stage (P<0.05). The expression levels of UBAC2 mRNA and protein in multiple colorectal cancer cell lines were significantly higher than those in normal colonic epithelial cells (P<0.05). Compared with sh-NC group, sh-UBAC2 group showed significantly increased E-cadherin protein expression, significantly decreased N-cadherin and Vimentin protein expression, and significantly reduced number of invaded and migrated SW480 cells (P<0.05). GEPIA2.0 database analysis results indicated a positive correlation between WTAP and UBAC2 expression (r=0.24, P<0.001). Compared with si-NC group, si-WTAP group showed significantly decreased expression levels of WTAP and UBAC2 mRNA and protein in SW480 cells (P<0.05). MeRIP-qPCR results demonstrated that the m6A modification level of UBAC2 mRNA in si-WTAP group was significantly lower than that in si-NC group (P<0.05). RIP-qPCR further confirmed that WTAP could bind to UBAC2 mRNA. Compared with control group, si-WTAP group showed significantly increased E-cadherin protein expression and significantly decreased N-cadherin and Vimentin protein expression in SW480 cells (P<0.05); compared with si-WTAP group, si-WTAP+OE-UBAC2 group showed significantly decreased E-cadherin protein expression and significantly increased N-cadherin and Vimentin protein expression in SW480 cells (P<0.05). The number of lung nodules in LV-sh-UBAC2 group was significantly fewer than that in LV-sh-NC group, and the expression level of Luc2 mRNA in lung tissues was significantly lower than that in LV-sh-NC group (P<0.05).ConclusionUBAC2 mediated by m6A methylation modification can regulate the epithelial-mesenchymal transition (EMT) process in colorectal cancer cells, thereby affecting the invasion and migration abilities of colorectal cancer cells.
关键词:colorectal cancer;ubiquitin-associated domain-containing protein 2;N6-methyladenosine;Wilms tumor 1-associated protein;invasion;migration
摘要:Inhalation therapy, as a drug delivery method directly targeting the respiratory tract and lungs, has been widely used in the treatment of respiratory diseases due to its characteristics of efficient drug delivery, rapid onset, and low systemic side effects. However, traditional inhalation particles still have some limitations in drug stability, release control, and pulmonary delivery efficiency. In recent years, with the continuous development of biochemical materials, the performance of new inhaled particles has been significantly improved, which can provide better drug-loading capacity, more precise release control, and more efficient pulmonary delivery, showing great potential in improving drug efficacy and reducing side effects. This review comprehensively summarizes the classification, preparation techniques, and applications of inhalable particles. It further explores their prospects in precise therapy, personalized medication, and the next-generation drug delivery systems, aiming to promote research and technological innovation in inhalation therapy, ultimately advancing therapeutic solutions for respiratory diseases.
摘要:Parkinson's disease (PD) is a common neurodegenerative disease characterized by degeneration of dopaminergic neurons in the substantia nigra, abnormal aggregation of α-synuclein and neuroinflammation. Therapeutic methods including drug intervention have limited efficacy. In recent years, the role of gut microbiota-brain axis in the pathogenesis of PD has received extensive attention. Butyrate acid, as a short-chain fatty acid produced by intestinal microbiota, has been demonstrated to exert certain role in PD prevention and treatment. This review discusses the molecular mechanism of butyrate acid in PD, its potential therapeutic effect and its clinical application in the treatment of PD patients from the perspective of regulating neuroinflammation, mitigating mitochondrial dysfunction, regulating oxidative stress, maintaining intestinal epithelial integrity and blood-brain barrier permeability, in order to provide reference for the research on prevention and treatment of PD.
摘要:Diabetic kidney disease (DKD) is a microvascular complication of diabetes mellitus with a complex pathogenesis. Recent studies have revealed that autophagy and ferroptosis, as two forms of programmed cell death, exhibit dynamic interactions in DKD: autophagy maintains homeostasis by eliminating damaged organelles, while ferroptosis is driven by iron-dependent lipid peroxidation. Imbalance between the two exacerbates renal injury. This review systematically summarizes the signaling pathways and key regulatory factors related to autophagy and ferroptosis, as well as their interaction mechanisms [such as nuclear receptor coactivator 4 (NCOA4)-mediated ferritinophagy, clock autophagy, and lipid autophagy]. It further elaborates the molecular network by which these processes synergistically regulate DKD progression. Additionally, the potential of modern pharmaceuticals and active components of traditional Chinese medicine to improve kidney injury by targeting autophagy and ferroptosis is discussed, proposing that targeting their cross-talk pathways may provide novel therapeutic strategies for DKD, aiming to lay a theoretical foundation for the development of targeted intervention strategies and precision therapeutic regimens.
摘要:Spinal cord injury (SCI) is a central nervous system disease that can lead to motor, sensory, and autonomic dysfunction. Depending on the state of immune microenvironment, macrophage polarization can differentiate into M1/M2 phenotypes. The regulation of macrophage polarization by stem cells in many pathophysiological processes of SCI has become a hot topic of research in recent years. This review summarizes the relationship between macrophage polarization and SCI, and how mesenchymal stem cells (MSCs) and neural stem cells (NSCs) regulate macrophage polarization to improve SCI through paracrine secretion, delivery molecules, derived exosomes, and metabolic reprogramming pathways. It also summarizes the mechanism by which stem cells regulate the macrophage polarization phenotypes to promote SCI recovery through signaling pathways such as Janus tyrosine kinase/signal transducer and activator of transcription (JAK/STAT), Notch, Toll-like receptor 4/nuclear factor kappa-B (TLR4/NF-κB), phosphatidylinositol 3 kinase/protein kinase B (PI3K/Akt). The aim is to provide theoretical support for the treatment of SCI by regulating macrophage polarization with stem cells and to offer new perspectives for exploring the mechanism of stem cell therapy for SCI.