Objective To investigate the neuroprotective effect of TGP on PS rats and determine the impact on the Ste20-like proline/alanine-rich kinase/Na+-K+-Cl cotransport(SPAK/NKCC1)signaling pathway.Methods After PS model was successfully established in 60 male SD rats(7 weeks old),they were randomly divided into model group,low-and high-dose TGP groups,high-dose TGP+negative control group,and high-dose TGP+WNK3 overexpression group,with 12 rats in each group.Another 12 healthy rats served as the control group.After modeling,50 or 200 mg/kg TGP was given to the rats of corresponding groups intragastrically,the overexpression plasmids of WNK3 were given to the rats from the high-dose TGP+WNK3 overexpression group through tail vein injection,and same volume of normal saline was given to the control group.All of these agents were administrated once per day for 7 consecutive days.ELISA was applied to de-tect serum levels of IL-6,IL-1β,MDA and SOD.HE staining was applied to detect the pathological morphology of the substantia nigra region in brain tissue.TUNEL staining was used to observe neuronal apoptosis.Immunohistochemistry was conducted to measure the expression of α-synucle-in(α-syn),and Western blotting for the expression of Bax,Bcl-2 and SPAK/NKCC1 signaling pathway related proteins(WNK3,p-SPAK,SPAK,p-NKCC1 and NKCC1).Results Compared with the model group,the pathological damage of neurons in substantia nigra was reduced in low-and high dose TGP groups,reduced contents of IL-6,IL-1β and MDA,lower neuronal apoptotic rate,and declined expression of Bax,α-syn,WNK3,p-SPAK/SPAK,and p-NKCC1/NKCC1,but raised SOD content and Bcl-2 expression level(88.39±8.96 U/mg,119.57±12.01 U/mg vs 60.28±6.14 U/mg,P＜0.05;0.57±0.06,0.82±0.09 vs 0.38±0.04,P＜0.05).The intervention with WNK3 overexpression resulted in more severe pathological damage to neurons in the sub-stantia nigra,increased contents of IL-6,IL-1β and MDA,higher neuronal apoptotic rate,enhanced expression of Bax,α-syn,WNK3,p-SPAK/SPAK,and p-NKCC1/NKCC1,and reduced SOD con-tent and Bcl-2 expression level when compared with the high-dose TGP+negative control group(P＜0.05).Conclusion TGP exerts neuroprotective effects on PS rats,and its mechanism is re-lated to the inhibition of the SPAK/NKCC1 signaling pathway.

Objective To investigate the neuroprotective effect of TGP on PS rats and determine the impact on the Ste20-like proline/alanine-rich kinase/Na+-K+-Cl cotransport(SPAK/NKCC1)signaling pathway.Methods After PS model was successfully established in 60 male SD rats(7 weeks old),they were randomly divided into model group,low-and high-dose TGP groups,high-dose TGP+negative control group,and high-dose TGP+WNK3 overexpression group,with 12 rats in each group.Another 12 healthy rats served as the control group.After modeling,50 or 200 mg/kg TGP was given to the rats of corresponding groups intragastrically,the overexpression plasmids of WNK3 were given to the rats from the high-dose TGP+WNK3 overexpression group through tail vein injection,and same volume of normal saline was given to the control group.All of these agents were administrated once per day for 7 consecutive days.ELISA was applied to de-tect serum levels of IL-6,IL-1β,MDA and SOD.HE staining was applied to detect the pathological morphology of the substantia nigra region in brain tissue.TUNEL staining was used to observe neuronal apoptosis.Immunohistochemistry was conducted to measure the expression of α-synucle-in(α-syn),and Western blotting for the expression of Bax,Bcl-2 and SPAK/NKCC1 signaling pathway related proteins(WNK3,p-SPAK,SPAK,p-NKCC1 and NKCC1).Results Compared with the model group,the pathological damage of neurons in substantia nigra was reduced in low-and high dose TGP groups,reduced contents of IL-6,IL-1β and MDA,lower neuronal apoptotic rate,and declined expression of Bax,α-syn,WNK3,p-SPAK/SPAK,and p-NKCC1/NKCC1,but raised SOD content and Bcl-2 expression level(88.39±8.96 U/mg,119.57±12.01 U/mg vs 60.28±6.14 U/mg,P＜0.05;0.57±0.06,0.82±0.09 vs 0.38±0.04,P＜0.05).The intervention with WNK3 overexpression resulted in more severe pathological damage to neurons in the sub-stantia nigra,increased contents of IL-6,IL-1β and MDA,higher neuronal apoptotic rate,enhanced expression of Bax,α-syn,WNK3,p-SPAK/SPAK,and p-NKCC1/NKCC1,and reduced SOD con-tent and Bcl-2 expression level when compared with the high-dose TGP+negative control group(P＜0.05).Conclusion TGP exerts neuroprotective effects on PS rats,and its mechanism is re-lated to the inhibition of the SPAK/NKCC1 signaling pathway.

Objective To investigate the role of Glycoprotein non-metastatic melanoma protein B(GPNMB)in hypoxia-induced epithelial-mesenchymal transition(EMT)in human chorionic trophoblast HTR-8/SVneo cells.Methods HTR-8/SVneo cells were cultured in vitro to investigate the effect of hypoxia on GPNMB expression.The cells were transfected with either a GPNMB overexpression plasmid(pcDNA3.1-GPNMB),small interfering RNA targeting GPNMB(si-GPNMB-1/2),or their respective negative controls(pcDNA3.1-NC or si-NC),and were also treated with the autophagy agonist rapamycin(Rap).The experimental groups were categorized as follows:Normoxia,Hypoxia,Normoxia/Hypoxia+si-NC or si-GPNMB,Normoxia/Hypoxia+pcDNA3.1-NC or pcDNA3.1-GPNMB,Normoxia/Hypoxia+Rap,and Hypoxia+Rap+pcDNA3.1-NC or pcDNA3.1-GPNMB.GPNMB expression levels were evaluated using qRT-PCR,Western blotting,and immunofluorescence staining.The expression of autophagy-related proteins(LC3B Ⅱ/Ⅰ,p62)and epithelial-mesenchymal transition(EMT)markers(E-cadherin,N-cadherin)was analyzed by Western blotting.Cell migration and invasion capacities were assessed using wound healing and Transwell assays.Results Compared with the Normoxia group,the mRNA and protein levels of GPNMB were downregulated in the Hypoxia group.Additionally,the protein levels of p62 and N-cadherin were reduced,while LC3B Ⅱ/Ⅰ and E-cadherin expression levels were increased(P<0.05).Compared with the Hypoxia+si-NC group,the Hypoxia+si-GPNMB-2 group showed significantly decreased protein levels of p62 and N-cadherin,along with elevated levels of LC3B Ⅱ/Ⅰ and E-cadherin(P<0.05).Compared with the Hypoxia+pcDNA3.1-NC group,the Hypoxia+pcDNA3.1-GPNMB group exhibited opposite trends.Notably,compared with the Hypoxia group,the Hypoxia+Rap group showed increased LC3B Ⅱ/Ⅰ and E-cadherin levels,accompanied by reduced p62 and N-cadherin levels(P<0.05).However,compared with the Hypoxia+pcDNA3.1-GPNMB group,the Hypoxia+Rap+pcDNA3.1-GPNMB group attenuated the promoting effect of GPNMB overexpression on EMT in HTR-8/SVneo cells,as evidenced by decreased p62 and N-cadherin protein expression levels and increased LC3BⅡ/Ⅰ and E-cadherin protein expression levels(P<0.05).Conclusion In hypoxia-induced HTR-8/SVneo cells,GPNMB inhibits autophagy,promotes the epithelial-mesenchymal transition,and enhances cell migration and invasion.

Objective:To evaluate the levels and source of cadmium exposure by dietary pathway among middle-aged and elderly people ≥40 in cadmium-contaminated areas of China.Methods:A total of 7 193 people aged 40-89 years from four typical cadmium-contaminated areas in China were selected as the study subjects. Food Frequency Questionnaire (FFQ), Total Diet Study (TDS) and a 3-day-24-hour dietary recall survey were conducted. Dietary cadmium intake and food sources through dietary pathways were assessed based on cadmium content in foods, consumption amounts and intake frequencies.Results:The mean age of the participants was 63.39±12.21 years, with 50.05% being males. The average monthly dietary cadmium intake was 7.39 μg/(kg·BW). Staple foods and vegetables were the primary sources of dietary cadmium intake, accounting for 57.51% and 32.48%, respectively. The monthly dietary cadmium intake in all surveyed regions did not exceed the Provisional Tolerable Monthly Intake (PTMI) recommended by the Joint FAO/WHO Expert Committee on Food Additives (JECFA).Conclusion:The monthly dietary cadmium intake among middle-aged and elderly people in cadmium-contaminated areas of China is relatively low, with the risk remaining at an acceptable level. Staple foods and vegetables are the most significant contributors to dietary cadmium intake.

Objective:To determine the optimal cut-off value of serum cotinine for distinguishing smoking status among Chinese adults based on a large-scale national sample.Methods:A cross-sectional study was conducted among 8 987 Chinese adults aged 20-79 years from 152 administrative counties across 31 provinces during 2017-2018. Sociodemographic characteristics, lifestyle, smoking status, and health status were collected via questionnaires and physical examinations. Blood samples were analyzed for serum cotinine levels using liquid chromatography-mass spectrometry and for blood creatinine levels using the picric acid method. Receiver operating characteristic (ROC) curve analysis was performed with serum cotinine concentration as the test variable and self-reported smoking status as the state variable. The optimal cut-off value was determined based on the maximum Youden′s index, and the bootstrap method was used for repeated sampling (2 000 times) to evaluate the confidence interval of the cut-off value. The net reclassification index (NRI) was used to evaluate the discrimination ability of the cut-off value of this study, the cut-off value of the American population 1 (total population: 3.3 μg/L, men: 4.1 μg/L, women: 3.0 μg/L) and the cut-off value of the American population 2 (the recommended value of the United States Centers for Disease Control and Prevention for the total population: 10.0 μg/L) against the smoking status of the Chinese population. Statistical analyses were conducted using IBM SPSS 27 and Python 3.11, with a significance level of α=0.05.Results:The age of the research subjects was (49.2±15.2) years. Among them, males accounted for 49.8% (4 477); smokers accounted for 28.8% (2 586); the detection rate of serum cotinine was 94.6% (8 501), and the M ( Q1, Q3) concentration of serum cotinine was 0.9 (0.3, 85.4) μg/L. The ROC curve analysis results showed that the cut-off value (95% CI) of serum cotinine in the total population was 8.8 (6.7-11.7) μg/L, with the specificity (95% CI) about 93.6%(92.7%-94.3%), the sensitivity (95% CI) about 91.0%(89.7%-92.3%) and the area under the curve (AUC) (95% CI) about 0.93 (0.92-0.94). The cut-off value (95% CI) of cotinine for males was 17.1 (8.8-21.8) μg/L, with the specificity (95% CI) about 90.7%(87.9%-92.0%), the sensitivity (95% CI) about 89.4%(88.4%-92.2%) and the AUC (95% CI) about 0.92 (0.91-0.93). The cut-off value (95% CI) of cotinine for females was 7.4 (3.3-15.0) μg/L, with the specificity (95% CI) about 95.6%(92.7%-96.8%), the sensitivity (95% CI) about 87.6%(81.6%-92.8%) and the AUC (95% CI) about 0.92 (0.87-0.95). The NRI analysis results showed that compared with the cut-off value of the American population 2, the NRI of this study′s cut-off values in the total population, males and females were 0.020 ( P=0.015), 0.033 ( P=0.015) and 0.011 ( P=0.380), respectively, indicating that this study′s cutoff value could have better classification performance in the total population and males. Compared with the cut-off value of the American population 2, the NRI of the total population in this study was 0.001 ( P=0.285). Conclusion:The serum cotinine cut-off value based on the analysis of large sample data in China is more suitable for distinguishing the smoking status of Chinese adults.

Objective:To investigate the association between blood selenium levels and sex hormones in Chinese men aged 18-79 years.Methods:Data were derived from the China National Human Biomonitoring survey conducted in 2017-2018, with a final sample size of 5 414 men. General demographic characteristics, behavioral habits, and dietary frequency were collected through questionnaires and physical examinations. Fasting blood samples were collected to measure blood lead, serum testosterone, and estradiol levels. Complex sampling linear regression models were used to analyze the associations between blood selenium levels and testosterone, estradiol, and the testosterone/estradiol ratio, adjusting for confounding factors including age, education level, marital status, smoking status, alcohol consumption, seafood intake, soy product intake, protein supplement intake, BMI, and diabetes status.Results:The mean age of the 5 414 participants was (46.85±27.91) years; 4 774 (91.65%) were of Han ethnicity and 4 505 (86.68%) were married. The median ( Q1, Q3) blood selenium concentration in men was 97.80 (80.64, 116.99) μg/L. After adjusting for confounding factors, the complex sampling linear regression model revealed negative associations between blood selenium levels and both testosterone levels and the testosterone/estradiol ratio, with a significant linear trend ( Ptrend<0.05). Compared with the Q1 group, the β (95% CI) values for testosterone in the Q2, Q3, and Q4 groups were -0.02 (-0.06 to 0.02), -0.03 (-0.08 to 0.01), and -0.06 (-0.09 to -0.02), respectively. Similarly, the β (95% CI) values for the testosterone/estradiol ratio in the Q2, Q3, and Q4 groups were -0.01 (-0.03 to 0.02), -0.01 (-0.04 to 0.04), and -0.03 (-0.06 to -0.01), respectively. Subgroup analysis indicated stronger associations between blood selenium levels and testosterone/estradiol levels in non-smoking and obese men (BMI≥28 kg/m2). Conclusion:Blood selenium levels are negatively associated with testosterone levels and the testosterone/estradiol ratio in Chinese adult males.

Objective To construct a prediction model of epidermal growth factor receptor(EGFR)gene mutation in patients with non-small cell lung cancer(NSCLC)based on spectral CT parameters,lymphocyte to monocyte ratio(LMR)and systemic inflam-mation response index(SIRI).Methods The spectral CT parameters,LMR and SIRI of EGFR mutant and wild types NSCLC patients were compared,respectively.The influencing factors of EGFR gene mutation were analyzed and a risk prediction model was estab-lished.Results The LMR,70 keV CT value in arterial phase and venous phase,normalized iodine concentration(NIC),slope of spectral curve(λHU)and venous phase ΔCT value in EGFR mutant type patients were significantly higher than those in EGFR wild type patients,while SIRI,arterial phase and venous phase normalized water concentration(NWC)were significantly lower than those in EGFR wild type patients(P<0.05).Female,adenocarcinoma,no smoking history,LMR,increased NIC,λHU,and ΔCT value in venous phase were the risk factors for EGFR gene mutation,and increased SIRI was a protective factor(P<0.05).The decision curve showed that when the risk threshold was 0.2-0.6,the prediction model had a good risk-benefit ratio.The P value of Hosmer-Lemeshow goodness of fit test was 0.519,and the area under the curve for predicting EGFR gene mutation in NSCLC patients was 0.911.Conclusion Spectral CT parameters,LMR and SIRI may be associated with EGFR gene mutation in NSCLC patients,the model constructed based on the above indicators has a high predictive efficacy for EGFR gene mutation.

Objective To investigate the value of adjusting antiplatelet treatment regimens guided by thromboelastography(TEG)in predicting cerebral ischemic events after stent-assisted embolization of intracranial aneurysms.Methods This study retrospectively and consecutively enrolled patients with intracranial aneurysms who underwent stent-assisted coil embolization admitted to the Department of Neurosurgery of the General Hospital of Eastern Theater Command,from March 2022 to May 2024.Baseline and clinical data of the patients,including gender,age,hypertension,diabetes,dyslipidemia,smoking history,drinking history,and intraoperative use of tirofiban were collected.Antiplatelet therapy(conventional dose aspirin[100 mg once daily]+clopidogrel[75 mg once daily])was initiated immediately after the diagnosis of intracranial aneurysm,and TEG was performed 3 days later.According to the platelet inhibition rate in TEG parameters(platelet inhibition rate induced by arachidonic acid[AA]pathway[AA inhibition rate]or adenosine diphosphate[ADP]pathway[ADP inhibition rate],AA inhibition rate ≥ 50％indicated aspirin effectiveness,AA inhibition rate＜50％indicated aspirin resistance;ADP inhibition rate ≥ 30％indicated clopidogrel effectiveness,ADP inhibition rate＜30％indicated clopidogrel resistance),the patients were divided into the control group(TEG test results met the criteria,i.e.,AA inhibition rate ≥ 50％and ADP inhibition rate ≥ 30％),the conventional dual antiplatelet therapy group(TEG test results did not meet the criteria but were not adjusted for antiplatelet therapy,i.e.,AA inhibition rate＜50％and/or ADP inhibition rate＜30％,but with complex aneurysm morphology[such as irregular shape,daughter sac formation]or high bleeding risk,continuing conventional dual antiplatelet therapy),and the intensified group(TEG test results did not meet the criteria and the antiplatelet therapy regimen was adjusted,i.e.,AA inhibition rate＜50％and/or ADP inhibition rate＜30％,adjusting the antiplatelet therapy regimen).All patients underwent stent-assisted coil embolization after TEG testing.From 0 to 3 months after the operation,all three groups maintained the above antiplatelet therapy.At 3 months after the operation,routine head MRI,CT and other examinations were performed.If no cerebral ischemic events occurred and the imaging results were satisfactory(good stent position,no aneurysm occlusion residual or slight residual at the neck[neck width of the aneurysm 2mm]),the treatment could be adjusted to single antiplatelet therapy(aspirin 100 mg once daily).If a patient experienced a cerebral ischemic event during the follow-up period,regardless of the stage after the operation,dual antiplatelet therapy(aspirin[100mg once daily]+clopidogrel[75 mg once daily])was immediately restarted or maintained and continued for at least 6 months.The primary endpoint was intraoperative and 6-months postoperative cerebral ischemic events(including DSA-confirmed intraoperative acute thrombosis and infarction foci confirmed by head CT or MRI).Baseline and clinical data of the three groups were compared.All patients were divided into groups with ischemic stroke event and without according to the primary endpoint,univariate Logistic regression analysis was then performed on both groups.Variables with P＜0.1 in the univariate Logistic regression analysis were included in the multivariate Logistic regression analysis to explore the influencing factors of cerebral ischemic events after stent-assisted coil embolization for intracranial aneurysms.Results A total of 499 patients were included,including 178 males and 321 females,with a median age of 59(53,68)years.Among them,there were 341 patients in the control group,42 in the conventional dual antiplatelet therapy group,and 116 in the intensified group.There were 47 cases of cerebral ischemic events and 452 cases without cerebral ischemic events.There was a statistically significant difference in the intraoperative use rate of tirofiban across the control group,the conventional dual antiplatelet therapy group,and the intensified group(20.2％[69/341]vs.26.2％[11/42]vs.42.2％[49/116],P＜0.01);no statistically significant differences were observed among the three groups in terms of age,gender composition,the proportion of patients with hypertension,diabetes,dyslipidemia,smoking history,drinking history,and the incidence of cerebral ischemic events(all P＞0.05).The results of multivariate Logistic regression analysis showed that hypertension(OR,2.924,95％CI 1.416-6.037,P=0.004)and intraoperative use of tirofiban(OR,3.638,95％CI 1.892-6.996,P＜0.01)were independent risk factors for intraoperative and 6-months postoperative cerebral ischemic events after stent-assisted coil embolization in patients with intracranial aneurysms.In comparison with the control group,the intensified group has reduced the risk of cerebral ischemic events(OR,0.238,95％CI 0.088-0.646,P=0.005),while there was no statistically significant difference between the conventional dual antiplatelet therapy group and the control group(OR,0.521,95％CI 0.149-1.826,P=0.308).Conclusions This study demonstrates that adjusting the antiplatelet therapy regimens in patients with intracranial aneurysms who did not meet the platelet inhibition rate based on TEG results can significantly reduce the risk of intraoperative and 6-months postoperative cerebral ischemic events.These finding may require validation through further,large-scaled,prospective studies.

Purpose: The genomic characteristics of uterine sarcomas have not been fully elucidated. This study aimed to explore the genomic landscape of the uterine sarcomas (USs). Materials and Methods: Comprehensive genomic analysis through RNA-sequencing was conducted. Gene fusion, differentially expressed genes (DEGs), signaling pathway enrichment, immune cell infiltration, and prognosis were analyzed. A deep learning model was constructed to predict the survival of US patients. Results: A total of 71 US samples were examined, including 47 endometrial stromal sarcomas (ESS), 18 uterine leiomyosarcomas (uLMS), three adenosarcomas, two carcinosarcomas, and one uterine tumor resembling an ovarian sex-cord tumor. ESS (including high-grade ESS [HGESS] and low-grade ESS [LGESS]) and uLMS showed distinct gene fusion signatures; a novel gene fusion site, MRPS18A–PDC-AS1 could be a potential diagnostic marker for the pathology differential diagnosis of uLMS and ESS; 797 and 477 uterine sarcoma DEGs (uDEGs) were identified in the ESS vs. uLMS and HGESS vs. LGESS groups, respectively. The uDEGs were enriched in multiple pathways. Fifteen genes including LAMB4 were confirmed with prognostic value in USs; immune infiltration analysis revealed the prognositic value of myeloid dendritic cells, plasmacytoid dendritic cells, natural killer cells, macrophage M1, monocytes and hematopoietic stem cells in USs; the deep learning model named Max-Mean Non-Local multi-instance learning (MMN-MIL) showed satisfactory performance in predicting the survival of US patients, with the area under the receiver operating curve curve reached 0.909 and accuracy achieved 0.804. Conclusion USs harbored distinct gene fusion characteristics and gene expression features between HGESS, LGESS, and uLMS. The MMN-MIL model could effectively predict the survival of US patients.

In order to further standardize the vaccination of kidney transplant candidates and recipients in China, the Branch of Organ Transplantation of Chinese Medical Association has organized experts in kidney transplantation and infectious diseases. Based on the "Vaccination of Solid Organ Transplant Candidates and Recipients: Guidelines from the American Society of Transplantation Infectious Diseases Community of Practice", and in combination with the clinical reality of infectious diseases and vaccination after organ transplantation in China, as well as referring to relevant recommendations from home and abroad in recent years, these guidelines are formulated from aspects such as epidemiology, types of vaccines, vaccination principles, target population, and specific vaccine administration. The "Guidelines for Vaccination of Kidney Transplant Candidates and Recipients in China" aims to provide theoretical reference for medical workers in the field of kidney transplantation in China, regarding the vaccination of kidney transplant candidates and recipients. It is expected to better guide the vaccination of kidney transplant candidates and recipients, reduce the risk of postoperative infection, and improve survival outcomes.