摘要:ObjectiveTo explore the changing patterns of electrocardiogram (ECG) and echocardiography in healthy young people during their descent from high altitude to the plain.MethodsA prospective cohort study was carried out. Fifty-five healthy young volunteers who had migrated to an altitude of 4800-5500 m on the Qinghai-Tibet Plateau within one year were recruited as the plateau-migration group. ECG examinations were performed at an altitude of 3700 m (first time), on the 5th day after returning to 1300 m (second time), and on the 15th day after returning to 1300 m (third time). Echocardiography was conducted at 3700 m and on the 5th day after returning to 1300 m. A plain control group of 55 healthy youngsters from the plains (1300 m) was matched. The results of ECG and echocardiography between the two groups were compared.ResultsIntragroup analysis of the plateau-migration group revealed that compared with the first ECG results, the number of normal ECGs decreased in the second and third ECG results (P<0.05), and the proportions of sinus rhythm irregularity, sinus bradycardia, and U-wave appearance increased(P<0.05). There was no statistically significant difference in abnormal ECG results between the second and third ECGs (P>0.05). Compared with plain control group, there was no significant difference in the abnormal results of the first ECG of plateau-migration group (P>0.05). In the second and third ECG results, the number of normal ECGs was significantly reduced, and the proportions of sinus bradycardia, sinus rhythm irregularity, and U-wave appearance were significantly increased compared with plain control group (P<0.001). Intragroup analysis of plateau-migration group revealed that compared with the first ECG, the heart rate decreased in the second and third ECGs (P<0.05 or <0.001). Compared with plain control group, in the first ECG of plateau-migration group, the PR interval was significantly prolonged, the QTc interval was shortened, and the QRS axis degree was increased (P<0.05). In the second ECG, the heart rate significantly decreased, the PR interval was prolonged, and the QTc interval was shortened (P<0.05). In the third ECG, the heart rate decreased, the PR interval was prolonged, the QTc interval was shortened, and the QRS axis degrees was increased (P<0.05). The QRS axis of the first, second, and third ECGs of plateau-migration group was statistically significantly different from that of plain control group (P<0.001). Intragroup analysis of plateau-migration group showed that compared with the first echocardiogram, the left ventricular end-systole diameter, left ventricular end-diastolic diameter, and left atrial anteroposterior diameter all significantly increased in the second echocardiogram (P<0.001). Compared with plain control group, in the first echocardiogram of plateau-migration group, the left ventricular end-systole diameter and right atrial transection diameter significantly decreased, the right ventricular transection diameter significantly increased, and the left ventricular fractional shortening rate (FS) significantly decreased (P<0.05); In the second echocardiogram, the left atrial anteroposterior diameter, right atrial transverse diameter, and right ventricular transverse diameter all significantly increased, and FS increased (P<0.05).ConclusionsIn healthy young people returning from high altitude to the plain, as the altitude decreased, the heart rate significantly drops. The number of people with frontal QRS axis right deviation significantly reduces. The number of normal ECGs significantly decreases, while the numbers of people with sinus bradycardia, sinus arrhythmias, and U-wave appearance significantly increase. During high-altitude stay, the left ventricular systolic and diastolic function is affected to some extent.
关键词:de-adaptation to high altitude;plateau;plain;electrocardiogram;echocardiogram
摘要:ObjectiveTo explore the value of constructing a model to predict the number of positive cores in systematic biopsy in prostate cancer (PCa) using a combination of radiomics features based on magnetic resonance imaging and clinical indicators.(P<0.001). Univariate logistic regression analysis showed that FPSA (P<0.001), TPSA (P<0.001), FPSA/TPSA ratio (P=0.001), PSAD (P<0.001), and Radscore (P<0.001) were risk factors for positive cores in systematic biopsy in PCa. Multivariate logistic regression analysis showed that PSAD (OR=0.251, 95%CI 0.063-0.996, P=0.049) and Radscore (OR=1.990, 95%CI 1.409-2.812,MethodsRetrospectively collected magnetic resonance imaging and clinical data from two medical institutions (Gansu Provincial Hospital from January 2018 to February 2023, Zhangye People's Hospital Affiliated to Hexi College from April 2020 to February 2023). The 155 patients from Gansu Provincial Hospital were randomly divided into a training set (n=109; 80 cases with positive needle count ≥6 and 29 cases with positive needle count <6) and an internal validation set (n=46; 34 cases with positive needle count ≥6 and 12 cases with positive needle count <6) in a 7:3 ratio. The 43 patients from Zhangye People's Hospital Affiliated to Hexi College were used as external validation set. Small field of view high-resolution T2-weighted imaging (sFOV HR-T2WI) and contrast-enhanced delayed-phase images were selected to extract radiomic features from the three-dimensional region of interest of the entire prostate, and radiomics model was constructed and Radscores calculated after dimensionality reduction and feature selection. Univariate and multivariate logistic regressions were used to screen for independent risk factors for positive cores in systematic biopsy. Nomogram was constructed using Radscore and clinical independent risk factors to predict the number of positive cores in systematic biopsy in PCa patients, which was then externally validated.ResultsAge, alkaline phosphatase (ALP), free prostate specific antigen (FPSA), total prostate specific antigen (TPSA), FPSA/TPSA ratio, and prostate specific antigen density (PSAD) were not statistically significantly different between the training, internal validation, and external validation sets (P>0.05). FPSA, TPSA, FPSA/TPSA ratio, and PSAD were significantly different between the positive cores <6 and positive cores ≥6 groupsP<0.001) were independent risk factors for positive cores in systematic biopsy in PCa. The clinical models achieved AUCs of 0.849(95%CI 0.774-0.924), 0.817(95%CI 0.693-0.941), and 0.631(95%CI 0.439-0.822); the 12 features for radiomics models are derived solely from sFOV HR-T2WI, the radiomics models achieved AUCs of 0.868(95%CI 0.791-0.945), 0.846(95%CI 0.695-0.996), and 0.815(95%CI 0.660-0.970); the nomogram achieved AUCs of 0.921(95%CI 0.869-0.973), 0.868(95%CI 0.743-0.992), and 0.840(95%CI 0.702-0.978) in the training set, internal validation set, and external validation set, respectively.ConclusionsThe combination of radiomic features extracted from sFOV HR-T2WI and PSAD can preoperatively be used as a noninvasive manner to predict the number of positive cores of the PCa patients. This approach has a certain value in risk stratification of PCa patients and guiding personalized clinical management.
关键词:prostate neoplasms;radiomics;magnetic resonance imaging;positive cores;prostate specific antigen density
摘要:ObjectiveTo explore the correlation between systemic family dynamics characteristics and adolescent depressive symptoms, and the mediating role of negative life events between them.MethodsA cross-sectional study was conducted on 124 adolescent patients diagnosed with depressive disorder according to the international classification of diseases (ICD)-10 criteria at the Psychosomatic Medicine Department of Shanghai East Hospital Affiliated to Tongji University from September 2021 to February 2023. The second edition of the Scale of Systematic Family Dynamics (SSFD), Children's Depression Inventory (CDI), and Adolescent Self-Rating Life Events Checklist (ASLEC) were utilized to evaluate the family dynamics characteristics, depressive symptoms, and negative life events. Canonical correlation analysis was performed to explore the relationships between 4 dimensions of SSFD [family atmosphere (FA), individuation (IN), system logic (SL), illness concept (IC)] and 5 factors of CDI (low self-esteem, negative emotion, anhedonia, inefficiency, interpersonal problem). A mediation effect analysis using Bootstrap test was conducted to analyze the mediating role of negative life events between family dynamics and adolescent depressive symptoms.ResultsThe scores for FA, SL, and IN in SSFD were negatively correlated with the total score of CDI (r=-0.359, -0.256, -0.291, P<0.01), and negatively correlated with the total score of ASLEC too (r=-0.318, -0.371, -0.406, P<0.01). However, a positive correlation was observed between the total scores of ASLEC and CDI (r=0.633, P<0.01). Canonical correlation analysis between the 4 dimensions of SSFD and the 5 factors of CDI revealed one pair of statistically significant canonical variables (U1, V1) with a canonical correlation coefficient of 0.483 (P<0.05). This indicates that the canonical variable U1 of SSFD was primarily influenced by FA, while the canonical variable V1 of CDI was mainly affected by low self-esteem and interpersonal problems. The mediating analysis showed that the effects of FA, IN, and SL scores on CDI total score were all weak (-0.147, -0.117, -0.102, respectively) but statistically significant (P<0.05). The direct effect of IN and SL scores on CDI total score was not statistically significant (P>0.05), while the direct effect of FA score on CDI total score was statistically significant (-0.076, P<0.05). Additionally, the mediating effect of ASLEC between the scores of FA, IN, SL and CDI total score were all significant (-0.071, -0.095, -0.087, respectively) (P<0.05).ConclusionsAdolescent depressive symptoms may be influenced by systemic family dynamics characteristics and negative life events. Negative life events mediate the influence of FA, IN, and SL on depressive symptoms. However, the IC is not related to depressive symptoms in adolescents.
关键词:adolescent;health;depression;family relations;negative life event;mediation
摘要:ObjectiveTo investigate the accuracy and clinical efficacy of 3D-printed patient-specific instruments (PSIs) in medial open-wedge high tibial osteotomy (MOWHTO) for the treatment of knee varus deformity and medial compartment osteoarthritis.MethodsClinical data of 69 patients with knee varus deformity and medial compartment ostecarthritis who underwent MOWHTO treatment in Department of Orthopedics, Fuyang People's Hospital Affiliated to Anhui Medical University from October 2017 to March 2021 were retrospectively analyzed. Patients were divided into two groups: 3D group using 3D-printed PSIs (n=37) and conventional group using standard procedures (n=32). The lateral hinge point error, medial osteotomy point error, osteotomy surface angle error, osteotomy depth error, intraoperative distraction angle, femoral tibial angle (FTA), proximal tibial medial angle (MPTA), knee rotation angle (KRA), posterior tibial slope (PTS), intraoperative weight-bearing line ratio (WBLR), and the last follow-up International Knee Documentation Committee (IKDC) score of the two groups were compared. The correlation between accuracy indicators and curative effect was analyzed using Spearman's rank correlation.ResultsThe follow-up time for the 3D group was 19-26 months, averaging (21.1±3.6) months; for the conventional group, it was 14-26 months, averaging (23.6±1.6) months. No significant differences were found between the two groups in lateral hinge point error, osteotomy depth error, intraoperative distraction angle, and the FTA, MPTA, KRA, PTS, IKDC score at the last follow-up (P>0.05). However, the 3D group showed significantly lower errors in medial osteotomy point, osteotomy surface angle, and intraoperative WBLR compared with conventional group (P<0.05). Spearman analysis revealed no correlation between IKDC score and aforementioned accuracy indicators (lateral hinge point error, medial osteotomy point error, osteotomy surface angle error, osteotomy depth error, intraoperative distraction angle, and WBLR) at the last follow-up (P>0.05).ConclusionsThe use of 3D-printed PSIs in MOWHTO offers a more precise advantage in certain positioning parameters, yet there are still deficiencies in determining WBLR. Compared to traditional MOWHTO surgery, the short-term outcome does not show any significant improvement.
关键词:medial open-wedge high tibial osteotomy;arthritis;varus;3D printed;accuracy
Lin Qing-Wei, Song Jing-Chun, Song Qing, Gao Yan, Li Hai-Ling, Zhang Wei, Zhang Yu-Xiang, Li Qing-Hua, Expert Group of Heatstroke Prevention and Treatment of Chinese PLA
摘要:ObjectiveTo investigate the characteristics of coagulation function changes in patients with exertional heat illness (EHI) at different core temperatures(Tc).MethodsA retrospective analysis was conducted on the clinical data of 346 EHI patients admitted to the emergency or intensive care units of 24 military hospitals from March 2021 to November 2022. According to the Tc at admission, patients were divided into 4 groups: Tc <39 ℃ group (n=223), 39 ℃ ≤Tc <40 ℃ group (n=60), 40 ℃ ≤Tc <41 ℃ group (n=35), 41 ℃ ≤Tc <42 ℃ group (n=17), and Tc ≥42 ℃ group (n=11). Based on the occurrence of heat stroke, the 346 EHI patients were further divided into heat stroke group (n=63) and non-heat stroke group (n=283). Basic information, complete blood count, coagulation function, liver and kidney function, and other laboratory indicators of the patients in each group were collected and statistically analyzed. Multifactorial logistic regression analysis was used to identify independent risk factors for the development of heat stroke in EHI patients. The diagnostic value of prothrombin time (PT), D-dimer, and platelet count for EHI patients developing heat stroke was assessed using the receiver operating characteristic (ROC) curve.ResultsWhen Tc exceeded 39 ℃, D-dimer levels in EHI patients increased significantly and further elevated with rising Tc (P<0.05). When Tc exceeded 40 ℃, platelet count and fibrinogen levels decreased, and PT was prolonged (P<0.05). When Tc exceeded 41 ℃, activated partial thromboplastin time (APTT) was significantly prolonged, and platelet count and fibrinogen level decreased (P<0.05). Multivariate logistics regression analysis showed that PT (OR=1.120, 95%CI 1.015-1.236), D-dimer (OR=1.322, 95%CI 1.129-1.549), and platelet count (OR=0.991, 95%CI 0.985-0.997) were independent risk factors for heat stroke (P<0.05). The area under the ROC curve (AUC) for D-dimer in diagnosing heat stroke was 0.796 (95%CI 0.732-0.860, P<0.001) with sensitivity and specificity of 69% and 80%, respectively, when D-dimer was greater than 0.9 μg/ml. The AUC for PT in diagnosing heat stroke was 0.708 (95%CI 0.628-0.788, P<0.001), with sensitivity and specificity of 42% and 97%, respectively, when PT was greater than 16.4 s. The AUC for platelet count in diagnosing heat stroke was 0.724 (95%CI 0.642-0.807, P<0.001), with the sensitivity and specificity of 52% and 94%, respectively, when the platelet count was less than 140×109/L.ConclusionsThe degree of Tc elevation in EHI patients is positively correlated with the severity of coagulation dysfunction. Prolonged PT, increased D-dimer level, and decreased platelet count are independent risk factors for the development of exertional heat stroke in EHI patients.
关键词:exertional heat illness;core temperature;coagulation function;D-dimer;prothrombin time
摘要:ObjectiveTo analyze the characteristics of drug resistance in patients with disseminated pulmonary tuberculosis, and provide references for the clinical development of individualized treatment plans.MethodsA retrospective analysis was conducted on 71 hospitalized patients with disseminated pulmonary tuberculosis treated at the Beijing Chest Hospital, Capital Medical University from January 2015 to January 2024. The susceptibility of Mycobacterium tuberculosis from these patients to 16 anti-tuberculosis drugs was detected using the microplate method for mycobacterial drug susceptibility testing. The study analyzed the culture results of Mycobacterium tuberculosis, drug susceptibility test results, initial treatment or re-treatment status, drug resistance, and differences in drug resistance types between initial and re-treated patients.ResultsAmong the 71 patients with disseminated pulmonary tuberculosis, there were 51 males (71.8%), and 58 cases (81.7%) of acute disseminated pulmonary tuberculosis, with an overall drug resistance rate to 16 anti-tuberculosis drugs of 38.0%. There was no statistically significant difference in the total drug resistance rate between re-treated patients and those undergoing initial treatment [52.2%(12/23) vs. 31.3%(15/48), P=0.089]. The top 7 drugs to which patients were resistant were streptomycin (Sm) and isoniazid (INH) with 13 cases each (18.3%), rifapentine (Rft) and isoniazid aminosalicylate (Pa) with 10 cases each (14.1%), rifampicin (RFP), rifabutin (Rfb), and capreomycin (Cm) with 9 cases each (12.7%). The top 6 drugs to which initially treated patients were resistant were Cm with 6 cases (12.5%), Sm with 5 cases (10.4%), Pa with 4 cases (8.3%), INH, clarithromycin (Clr), and p-aminosalicylic acid (PAS) with 3 cases each (6.3%). The top 7 drugs to which re-treated patients were resistant were INH with 10 cases (43.5%), Sm, RFP, and Rft with8 cases each (34.8%), Rfb with 7 cases (30.4%), Pa and levofloxacin (Lfx) with 6 cases each (26.1%). The overall mono-resistance rate, poly-drug resistance rate, and multidrug-resistant rate to 16 anti-tuberculosis drugs were 9.9%, 7.0%, and 11.3%, respectively; all mono-resistance patients were initially treated; there was no statistically significant difference in the poly-drug resistance rate between re-treated and initially treated patients (13.0% vs. 4.2%, P=0.591), but the multidrug-resistant rate was significantly higher in re-treated patients (30.4% vs. 2.1%, P=0.002).ConclusionDrug resistance in disseminated pulmonary tuberculosis is severe. Clinical physicians can develop personalized anti-tuberculosis treatment plans based on drug susceptibility test results.
摘要:ObjectiveTo investigate the value of CD66b+ tumor-associated neutrophils (TANs) and neutrophil to lymphocyte ratio (NLR) in evaluating the efficacy and prognosis of neoadjuvant chemotherapy (NACT) for breast cancer.MethodsOne hundred and sixty-seven patients of invasive breast cancer treated with NACT in the Department of Breast Surgery, the First People Hospital of Lianyungang from January 2015 to June 2020 were collected, and 40 cases of normal breast tissues were collected. Immunohistochemistry was used to detect the expression of CD66b in breast cancer tissues before NACT and normal breast tissues. Peripheral venous blood was taken from patients within 1 week before the first cycle of NACT, count neutrophils and lymphocytes were counted and their ratio (NLR) was calculated. The correlation between TANs and NLR and clinicopathologic features was analyzed by χ2 test. The influencing factors of efficacy of NACT were analyzed by univariate χ2 test and multivariate logistic analysis. Kaplan-Meier survival analysis and multivariate Cox analysis were used to determine the prognostic factors. The correlation between TANs and NLR was determined by Spearman test.ResultsThe expression of CD66b in breast cancer tissues was significantly higher than that in normal breast tissues (P<0.05), and it was diffusely distributed throughout the tumor (cancer nest and stroma were infiltrated). High infiltration of parenchymal TANs before NACT was correlated with high clinical stage, lymph node metastasis, and recurrence and metastasis (P<0.05). High NLR before NACT was closely related to high cT stage and recurrence and metastasis (P<0.05). NLR of peripheral blood (P=0.007), cT stage (P=0.041), estrogen receptor (ER) status (P=0.009), and human epidermal growth factor 2 (HER2) expression (P=0.020) were independent predictors for pathologic complete response (pCR). TANs (P=0.023), high clinical stage (P=0.040), and pCR (P=0.027) before NACT were independent risk factors for disease-free survival (DFS) of patients with invasive breast cancer. There was no correlation between NLR and TANs (r=0.14, P=0.071).ConclusionsLow infiltration of parenchymal TANs before NACT predicts a better prognosis for patients with breast cancer. Higher NLR in peripheral blood is associated with chemotherapy resistance.
关键词:breast cancer;neoadjuvant chemotherapy;tumor-associated neutrophils;neutrophil to lymphocyte ratio;pathologic complete response
摘要:ObjectiveTo investigate whether axillary lymph node dissection (ALND) can be exempted for young breast cancers with reference to the inclusion criteria of American College of Surgeons Oncology Group (ACOSOG) Z0011 trial.MethodsA retrospective analysis was conducted on 134 cases of young breast cancer patients admitted to the Second Affiliated Hospital of Nanchang University and the Affiliated Hospital of Jiujiang College from February 28, 2013 to February 28, 2018 who met the inclusion criteria of the ACOSOG Z0011 trial. Patients were divided into case group [n=63, with sentinel lymph node biopsy (SLNB)] and control group (n=71, with SLNB and ALND). General clinicopathologic data, including age, tumor TNM stage, pregnancy or breastfeeding status, estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2), Ki-67, vessel carcinoma embolus, and tumor Nottingham grade, were collected and compared between the two groups. The 5-year disease-free survival (DFS) and 5-year overall survival (OS) of the two groups were analyzed using the Kaplan-Meier method with log-rank tests. A multifactorial Cox proportional hazards regression model was used to analyze the effect of SLNB implementation alone on the DFS and OS in young breast cancer.ResultsThere were no statistically significant differences in age, pregnancy or breastfeeding status, tumor T classification, tumour molecular classification, tumor Nottingham grade and vessel carcinoma embolus between the two groups (P>0.05). The 5-year DFS rate for the 134 young breast cancer patients was 74.6% and the 5-year OS rate was 83.6%. A statistically significant difference was observed in the 5-year DSF rate between case and control groups (66.7% vs. 81.7%, P=0.033), while there was no statistically significant difference in the 5-year OS rate (77.8% vs. 88.7%, P=0.085). The multifactorial Cox proportional hazards regression model analysis showed that performing SLNB alone was an independent risk factor for DFS in young breast cancer patients (HR=2.261, 95%CI 1.097-4.660, P=0.027), but not for OS (HR=1.976, 95%CI 0.789-4.946,P=0.146).ConclusionsYoung breast cancers exempted from ALND according to the ACOSOG Z0011 trial inclusion criteria had a higher rate of local recurrence, but their OS was not significant affected. Therefore, whether young breast cancers can be exempted from ALND still requires further clinical trial validation.
关键词:young breast cancer;ACOSOG Z0011 trial;disease-free survival;overall survival
Lu Guan-Jun, Wang Le-Xin, Zhao Jing, Liu Chao, Xiong Jian-Tuan, Jiao Yun, Yang An-Ning, Jiang Yi-Deng, Tian Yu-Jia, Xu Yao-Qin, Shi Qing, Liu Li, Zhang Ya-Lan, Bai Zhi-Gang, Li Shu-Juan
摘要:ObjectiveTo explore the regulatory role of transient receptor potential channel 6(TRPC6) on podocyte autophagy under the influence of homocysteine (Hcy) in mouse kidney.MethodsMouse renal podocytes were divided into control group and Hcy groups (stimulated by Hcy at 40, 60, 80 and 100 μmol/L for 48 h). The level of TRPC6 mRNA was assessed using quantitative reverse transcription polymerase chain reaction (qRT⁃PCR) to identify the optimal Hcy concentration for subsequent experiments. Western blotting was employed to evaluate the expression levels of autophagy-related proteins LC3 Ⅱ and p62, as well as the expression levels of podocyte structural proteins Nephrin and Podocin. The expression levels of TRPC6 mRNA and protein in both groups were determined using qRT-PCR, Western blotting and immunofluorescence. Transfections of cells with TRPC6 overexpression or interference were set as follows: (1) control group (untreated), negative control group of TRPC6 overexpression, and TRPC6 overexpression group; (2) control group (untreated), negative control group of TRPC6 interference, and TRPC6 interference group (si-1, si-2, si-3).The expression level of TRPC6 was detected using qRT⁃PCR. The cells after overexpressing or interfering of TRPC6 were further set as follows: (1) control group (untreated), Hcy group (80 μmol/L Hcy added), TRPC6 overexpression control+Hcy group, TRPC6 overexpression+Hcy group; (2) control group (untreated), Hcy group, TRPC6 interference control+Hcy group, and TRPC6 interference+Hcy group. The expression levels of p62, LC3 Ⅱ, and TRPC6 proteins were detected using Western blotting.ResultsqRT⁃PCR detection results showed that compared with control group, the expression level of TRPC6 mRNA in Hcy group increased with the increase of Hcy concentration, with the highest expression level observed at 80 μmol/L Hcy. Therefore, 80 μmol/L Hcy was selected as the optimal concentration for intervention. At this time, the expression level of autophagy-related protein LC3 Ⅱ increased, and the expression level of p62 decreased (P<0.05). Western blotting results showed that compared with control group, the expression levels of podocyte-related proteins Nephrin and Podocin in Hcy group were significantly decreased (P<0.05). qRT⁃PCR results showed that compared with control group, the expression level of TRPC6 mRNA in Hcy group was significantly increased (P<0.05). Compared with negative control group for TRPC6 overexpression, both mRNA and protein expression levels of TRPC6 in TRPC6 overexpression group were significantly higher (P<0.05). Compared with negative control group for TRPC6 interference, both mRNA and protein expression levels of TRPC6 in TRPC6 interference group were significantly decreased (P<0.05). Western blotting results showed that compared with negative control group for TRPC6 overexpression, the expression level of autophagy-related protein LC3 Ⅱ in TRPC6 overexpression+Hcy group was significantly increased, and the expression level of p62 was significantly decreased (P<0.05). Compared with TRPC6 negative control+Hcy group for TRPC6 interference+Hcy, the expression level of autophagy-related protein LC3 Ⅱ in TRPC6 interference+Hcy group was significantly decreased, and the expression level of p62 was significantly increased (P<0.05).ConclusionHcy can induce autophagy of renal podocytes. Inhibiting the expression of TRPC6 can significantly reduce the autophagy damage to podocytes.
摘要:ObjectiveTo investigate the viability of Runt-related transcription factor 1 (RUNX1) as a biomarker for gastric cancer and to assess the impact of the small molecule inhibitor Ro24-7429 on the proliferation, migration, and invasion of gastric cancer cells following targeted modulation.MethodsThrough the GEPIA database, we analyzed RUNX1 mRNA expression in gastric cancer or normal gastric tissues. Utilizing RUNX1 expression data from the TCGA database, a receiver operating characteristic (ROC) curve was constructed to appraise the potential of RUNX1 as a gastric cancer biomarker. In September 2022, we collected tissue samples from 6 patients with gastric cancer from the Department of General Surgery at the Second Hospital of Lanzhou University. After extracting tissue proteins, Western blotting was employed to compare RUNX1 protein expression in tumor and adjacent tissues. Gastric cancer cell lines with high RUNX1 expression were identified and the suppressive effect of the small molecule inhibitor Ro24-7429 on RUNX1 protein expression was verified by Western blotting. the effect of Ro24-7429 was validated by using CCK-8, colony formation, cell scratch, and Transwell assays. RUNX1 protein levels in gastric cancer tissues were quantified using immunohistochemical staining. An organoid model of gastric cancer was then established from the high-expression samples and verified by both HE and immunization analyses. Lastly, the impact of Ro24-7429 on the growth of gastric cancer organoids with meticulous tracking was evaluated using a biological microscope within a designated area.ResultsThe analysis from the GEPIA database revealed a heightened expression of RUNX1 mRNA in gastric cancer tissues compared with normal tissues (P<0.05). The ROC curve derived from the RUNX1 expression data in the TCGA database boasts an area under the curve (AUC) of 0.956, underscoring RUNX1's potential as a robust diagnostic marker. Western blotting results revealed significantly higher RUNX1 protein expression in gastric cancer tissues than in adjacent tissues (P<0.001). Among 5 gastric cancer cell lines studied, AGS and HGC27 exhibited pronounced RUNX1 protein expression (P<0.001). The small molecule inhibitor Ro24-7429, targeting RUNX1, potently suppressed RUNX1 expression in gastric cancer cells. The results from CCK-8, colony formation, scratch, and Transwell assays showed that Ro24-7429 effectively inhibited proliferation, migration, and invasion of gastric cancer cells (P<0.001). In a gastric cancer organoid model derived from high RUNX1 expression samples, the RUNX1 expression was remarkably consistent with its originating tissue. As expected, upon the targeted inhibition of RUNX1 using Ro24-7429, the cancer organoids significantly reduced growth capacity.ConclusionsRUNX1 shows potential as a biomarker for gastric cancer. Ro24-7429 specifically inhibits RUNX1 expression and suppresses tumor cell proliferation, migration, and invasion in gastric cancer cell lines and organoid models.
关键词:Runt-related transcription factor 1;Ro24-7429;gastric cancer cells;biological functions;organoid
摘要:ObjectiveTo investigate the improvement effect of 18kD translocator protein (TSPO) ligand YL-IPA08 on lipopolysaccharide (LPS)-induced depressive, anxiety-like behaviors and cognitive dysfunction in mice and the related anti-inflammatory mechanism.Methods(1) 50 male C57BL/6J mice were randomly divided into control group, LPS model group, LPS+YL-IPA08 (1.0 or 3.0 mg/kg) group and YL-IPA08 (3.0 mg/kg) group, with 10 mice in each group. Mice in LPS model group were intraperitoneally injected with LPS (0.5 mg/kg) once on day 1 and day 8. Mice in LPS+YL-IPA08 (1 or 3 mg/kg) and YL-IPA08 (3.0 mg/kg) groups were intragastrically administered YL-IPA08 (1.0 or 3.0 mg/kg) for 13 consecutive days, once a day. From the 9th to 12th day, the open field test, tail suspension test, forced swimming test, novel object recognition test and elevated-plus maze test were used to evaluate the depressive, anxiety-like behaviors and cognitive function of mice. Western blotting was used to detect the expression levels of postsynaptic density protein 95 (PSD95) and brain-derived neurotrophic factor (BDNF) in the prefrontal cortex of mice. (2) BV2 mouse microglia cells were divided into control group (phosphate buffered saline incubation for 1 h), LPS model group (incubated with 1.0 mg/L LPS for 6 h), LPS+YL-IPA08 (0.5 or 1.0 μmol/L) group (incubated with 0.5 or 1.0 μmol/L YL-IPA08 for 1 h and then incubated with 1 mg/L LPS for 6 h), and YL-IPA08 group (incubated with 1.0 μmol/L YL-IPA08 for 1 h). ELISA was used to detect the expression levels of inflammatory factors interleukin-1β (IL-1β), interferon-γ (IFN-γ), IL-4, IL-10 and transforming growth factor-β1 (TGF-β1). Western blotting was used to detect the expression levels of the members of Smad protein family (Smad2, Smad3) mediating signal transduction of TGF-β.Results(1) The results of behavioral experiments showed that there was no significant difference in the total movement distance of mice in each group in the open field test (P>0.05). Compared with the control group, the number of entries and duration time in the central area of mice in LPS model group were significantly decreased(P<0.05); the immobility time in the tail suspension test and the forced swimming test was significantly prolonged (P<0.05); the recognition index in the novel object recognition test, the percentage of entries into the open arms and the percentage of duration time in the open arm in the elevated-plus maze test were significantly decreased (P<0.05), and the expression levels of PSD95 and BDNF in the prefrontal cortex were significantly decreased (P<0.05). Compared with LPS model group, above behavioral and expression changes in LPS+YL-IPA08 (3.0 mg/kg) group were significantly reversed (P<0.05). (2) Compared with control group, the expression levels of pro-inflammatory factors IL-1β and IFN‑γ in BV2 cells in LPS model group were significantly increased (P<0.05), and the expressions of anti-inflammatory factors IL-4, IL-10 and TGF-β1 were significantly decreased (P<0.05), and the expression levels of Smad2 and Smad3 were significantly decreased (P<0.05). Compared with LPS model group, the expression level of IFN-γ in BV2 cells in LPS+YL-IPA08 (0.5 μmol/L) group was significantly decreased, and the expression levels of IL-4 and TGF-β1 were significantly increased (P<0.05); the above changes were significantly reversed in LPS+YL-IPA08 (1.0 μmol/L) group (P<0.05).ConclusionYL-IPA08 can significantly attenuate LPS-induced depressive and anxiety-like behaviors in mice and alleviate the decline in cognitive dysfunction, which mechanism may be related to improving neuroinflammation and regulating the TGF-β/Smad pathway.
摘要:ObjectiveTo investigate the correlation between DNA methyltransferase 3a (DNMT3a) expression and prognosis of lung squamous cell carcinoma (LSCC), as well as to elucidate the potential molecular mechanisms of DNMT3a in LSCC progression.MethodsA retrospective analysis was conducted on a cohort of 47 LSCC patients who underwent surgery in the Department of Thoracic Surgery, the Second Affiliated Hospital of Air Force Medical University between May 2009 and January 2014. DNMT3a expression in LSCC tissues and paired adjacent non-cancerous tissues was assessed using immunohistochemical (IHC) staining. Patients were categorized into two groups based on the median IHC score of DNMT3a in LSCC tissues: high DNMT3a expression group (n=25) and low DNMT3a expression group (n=22). Prognostic correlation was analyzed in combination with clinicopathological data and public biological databases. To explore the molecular mechanisms of DNMT3a in LSCC progression, H1703 LSCC cell lines with overexpressed DNMT3a were established using a lentiviral infection method, with the creation of DNMT3a overexpression group and control group. Functional phenotype experiments were then conducted to test the differences in cell proliferation and migration between the two groups. DNMT3a overexpression tumor xenograft models were also established in nude mice, with the creation of DNMT3a overexpression group and control group (3 mice per group), to observe the growth of subcutaneous xenograft tumors. Western blotting analysis was employed to detect the expression of related proteins in the two groups of cells and subcutaneous xenograft tumors. Functional rescue experiments involved treating DNMT3a overexpression cells with c-Myc inhibitor (10058-F4) and assessing cell proliferation using EdU proliferation staining. Subsequently, DNMT3a overexpression cells were infected with RNAi-Zinc finger E-box binding homeobox 1 (ZEB1) lentivirus to knock down ZEB1 expression, and a Transwell migration assay was utilized to detect cell migration. Finally, DNMT3a overexpression group and control group were treated with DNMT specific inhibitor (SGI-1027), and the effects of DNMT3a inhibition on cell proliferation and migration were observed in both overexpression and control groups.ResultsIHC analysis revealed significantly higher DNMT3a level in LSCC tissues compared to adjacent non-cancerous tissues (P<0.0001). High DNMT3a expression was closely associated with N stage, clinical stage and tumor differentiation degree (P<0.05 or P<0.01), and it was identified as an independent risk factor for poor prognosis in LSCC patients (P<0.05). Functional phenotype experiments indicated that DNMT3a overexpression group exhibited significantly higher colony formation number, proportion of EdU-positive cells, wound healing migration rate, and Transwell cell migration number compared with control group (P<0.05). The volume and weight of subcutaneous xenograft tumors in DNMT3a overexpression group were significantly higher than those in control group (P<0.001). Western blotting showed that the protein expression levels of c-Myc and ZEB1 in DNMT3a overexpression group were significantly higher than those in control group. Functional rescue experiments demonstrated a significant reduction in the proportion of EdU-positive cells after 10058-F4 treatment in DNMT3a overexpression group (P<0.05). Knockdown of ZEB1 led to a significant decrease in the number of Transwell cell migration in DNMT3a overexpression group (P<0.05), with no significant change in DNMT3a protein expression. Additionally, inhibition of DNMT3a with SGI-1027 resulted in a significant decrease in colony formation number and migration rate in both DNMT3a overexpression group and control group (P<0.05).ConclusionsHigh expression of DNMT3a is a significant independent risk factor for poor prognosis of LSCC patients. DNMT3a is likely to promote the proliferation of LSCC by upregulating c-Myc expression and to enhance the migration of LSCC by increasing ZEB1 expression.
摘要:Malnutrition is a significant risk factor for the progression of chronic kidney disease (CKD), and monitoring the nutritional status of CKD patients is crucial for delaying disease progression and improving patient prognosis. Currently, there is a scarcity of studies on malnutrition in CKD, and a unified standard for nutritional assessment in CKD is still lacking. Clinical evaluation must be conducted according to the condition of patients, combined with multiple indicators. Nutritional screening and assessment scales are the common nutritional assessment methods; however, due to limitations in the applicable populations, the applicability of some scales for the CKD population requires further verification. Additionally, anthropometric indicators, body composition analysis, and clinical laboratory indicators can also reflect human nutritional status, each with its respective advantages and limitations. This review summarizes the research status and clinical application characteristics of various nutritional assessment methods in CKD patients, aiming to provide references for the clinical assessment of malnutrition in CKD.
摘要:Cerebral small vessel disease (CSVD) is a group of local brain tissue lesions caused by abnormal small vessels in the brain due to different etiologies. The pathogenesis of CSVD is not yet fully understood, and its diagnosis currently mainly relies on clinical imaging examinations. Endothelial cells (ECs) in cerebral blood vessels can play an important role in maintaining the structure and function of the blood-brain barrier, regulating cerebral blood flow, and mediating neurovascular coupling. In recent years, studies have shown that ECs dysfunction plays an important triggering and mediating role in the pathological changes of CSVD, and may even be a key initiating link in its pathogenesis. Moreover, biomarkers related to ECs dysfunction are associated with the severity of CSVD. The review summarizes the role of ECs dysfunction in the pathogenesis of CSVD, and the research progress of related biomarkers, aiming to provide references for the diagnosis and treatment of CSVD.
摘要:Trastuzumab deruxtecan (T-DXd) is a new generation of antibody-drug conjugate targeting human epidermal growth factor receptor 2. It has strong antitumor effects and has been recommended by many authoritative guidelines at home and abroad. Drug-induced interstitial lung disease (DILD) is one of the common adverse reactions and causes of death of T-DXd and is an important factor limiting its clinical application. The pathogenesis of DILD induced by T-DXd is still unclear, and the mainstream view holds that it may be related to the non-target-dependent uptake of the drug. Glucocorticoids are an important treatment method for DILD, and other alternative drugs still lack clinical effectiveness evidence. The research progress on the pathogenesis of T-DXd induced DILD was summarized in this review, aiming to provide new ideas for the prevention and treatment of DILD.