Objective: To analyze factors impacting mental health status of medical students based on ecological systems theory, so as to provide reference for the mental health promotion system for medical students. Methods: In June 2024, 1 760 medical school students randomly selected from 19 different kinds of medical colleges in eastern China by stratified cluster were surveyed using questionnaires and expert interviews. Descriptive statistics, cross analysis, hierarchical linear regression analysis, structural equation models were used for data analysis. Results: Medical school students had higher satisfaction with the school (65.85%) and a great sense of perceived social support (57.16%). Furthermore, 91.14% of the students had normal interpersonal relationships. However, 44.89% reported that their mental health was impacted by high level of depression. The hierarchical linear regression analysis showed that the mental health outcomes of the medical students were positively predicted by higher perceived social support scores ( β =-11.40), institutional satisfaction ( β =-4.85 ), and lower help seeking stigma scores ( β =9.31) ( P <0.05). The structural equation modeling showed that the status of both perceived social support and self help seeking stigma had significant impacts on depression severity ( β =-0.32, -0.53) and interpersonal relationship sensitivity ( β =-0.31, 0.58) among medical students ( P <0.01).Through expert interviews, collaborations between the school and the tripartite organization (families, universities and society) was of growing importance. Conclusions Perceived social support and self stigma have a significant impact on the mental health status of medical students. The problem of self stigma of medical students should be paid attention to. Therefore, families, universities and society should work together to improve the mental health of medical students.

OBJECTIVE To investigate the effects of Tripterygium wilfordii multiglycoside （TWM） on renal injury in diabetic nephropathy （DN） rats through tumor protein p53/microRNA-214 （miR-214）/UNC-51-like kinase 1 （ULK1） axis. METHODS Male SD rats were randomly divided into normal group （n＝6） and modeling group （n＝28）； the modeling group was fed with high fat and high glucose plus intraperitoneal injection of streptozotocin to establish DN model. The modeled rats were randomly divided into model group， valsartan group [8.33 mg/（kg·d）] and TWM group[6.25 mg/（kg·d）]， with 8 rats in each group. Rats in each group were gavaged with the corresponding medication or normal saline， once a day， for 6 consecutive weeks. After the last medication， liver and renal function indexes [24 h urinary total protein （24 h-UTP）， blood urea nitrogen （BUN）， serum creatinine （SCr）， albumin （ALB）， alanine transaminase （ALT）]， blood lipid indexes （triglycerides， total cholesterol） and blood glucose index （fasting blood glucose） in urine/blood sample of rats were detected in each group. Renal pathologic change was observed， protein and mRNA expressions of p53， ULK1， Beclin-1 and microtubule-associated protein 1 light chain 3 （LC3）， and expression of miR-214 in renal tissue were also determined. RESULTS Compared with the normal group， the renal tubular epithelium of rats in the model group showed obvious edema， cell swelling， accompanied by lymphocyte infiltration； the levels of 24h-UTP， BUN， SCr， ALT and glycolipid indexes， the expressions of p53 protein and mRNA， as well as the expression of miR-214 in rats in the model group and administration groups were significantly increased or up-regulated， while ALB level， LC3-Ⅱ/LC3-Ⅰ， the expressions of LC3 mRNA， the expressions of ULK1， Beclin-1 protein and mRNA were significantly decreased or down-regulated （P＜0.01）. Compared with the model group， the histopathological damage of the kidney in rats was improved in administration groups； the levels of 24 h-UTP， BUN， SCr， ALT and glycolipid indexes， the expressions of p53 protein and mRNA， as well as the expression of miR-214 were all significantly decreased or down-regulated， while ALB level， LC3-Ⅱ/LC3-Ⅰ， the expressions of LC3 mRNA， the expressions of ULK1 and Beclin-1 protein and mRNA were significantly increased or up-regulated （P＜0.01）. CONCLUSIONS TG can alleviate renal damage in DN rats， and improve their liver and renal function， as well as glucose and lipid levels. These effects may be related to the regulation of the p53/miR-214/ULK1 axis and the restoration of cellular autophagy.

ObjectiveTo establish background data for a 90-day feeding trial of SD rats to ensure the reliability of research data. MethodsBackground data from six independent 90-day feeding trials of SD rats conducted by the National Center for Safety Evaluation of Drugs from 2020 to 2023 were summarized. These studies involved a blank control group of 120 SPF-grade 4-week-old SD rats, with an equal number of males and females, which were only given standard full-nutrient pelleted rat feed. After the quarantine period, the animals were observed for an additional 90 days, followed by intraperitoneal injection of Zoletil (50 mg/mL) for anesthesia, blood sampling, euthanasia, and necropsy. By analyzing the data from the blank control group, a relevant background database for SD rats was established. ResultsBoth male and female rats exhibited steady weight gain, with a more pronounced increase in male rats. Within 90 days, the average body weight of male and female rats increased to over 500 g and 300 g, respectively. Three weeks later, the average daily food intake of male rats stabilized at approximately 25~28 g per rat, while that of female rats remained stable at approximately 16~19 g per rat. The food utilization rate of all animals gradually decreased from the first week of the experiment. In the white blood cell (WBC) differential count results, significant differences were observed in the counts of WBCs, neutrophils (Neut), lymphocytes (Lymph), and monocytes (Mono) between males and females (P<0.001). However, there were no significant differences in the percentages of neutrophil (%Neut), lymphocyte (%Lymph), and monocyte (%Mono) between the sexes (P>0.05). The average red blood cell count (RBC), hemoglobin concentration (HGB), hematocrit (HCT), platelet count (PLT), prothrombin time (PT), and activated partial thromboplastin time (APTT) were higher in male animals than in female animals (P<0.05). The average values of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), creatine phosphokinase (CK), lactate dehydrogenase (LDH), glucose (GLU), and triglyceride (TG) in male rats were higher than those in female rats (P<0.05). The urinary pH range for male animals was 5.0 to 8.5, while for female animals it was 6.5 to 9.0. The majority of male animals had a urinary specific gravity lower than 1.020, and the majority of female animals had a urinary specific gravity lower than 1.015. The weights of various organs (excluding the adrenal glands and reproductive organs) in male animals were heavier than those in female animals (P<0.001), while the organ/body weight ratios (excluding the kidneys and reproductive organs) of female animals were higher than those of male animals (P<0.001). ConclusionThis study summarizes the background reference ranges for body weight, food intake, hematology, and serum biochemistry indicators in SPF-grade SD rats in the untreated control group from six 90-day feeding trials conducted by the National Center for Safety Evaluation of Drugs. It provides important reference data for related research. By summarizing the background and spontaneous histopathological changes in rats, this study aids in the standardization and normalization of subsequent research, as well as in the evaluation and analysis of abnormal results.

BackgroundSchizophrenia is a highly heterogeneous disease with different clinical subtypes. Artificial intelligence technology represented by deep learning models has provided considerable benefits for the electroencephalogram （EEG）-based schizophrenia diagnosis， treatment and research， however， to date little research has been conducted regarding any of these benefits among Chinese schizophrenic patients. ObjectiveTo investigate the application of deep learning techniques utilizing EEG parameters for the diagnosis of first-episode schizophrenia and grading of EEG abnormalities in patients， with the aim of contributing to improved clinical diagnosis and treatment strategies for the disorder. MethodsFrom January 2020 to January 2023， a total of 130 patients with first-episode schizophrenia who met the diagnostic criteria of International Classification of Diseases， tenth edition （ICD-10）， and attended at the Third People's Hospital of Fuyang， along with 150 health checkup examinees， were enrolled. All of them underwent EEG examination. An optimized long short-term memory （LSTM） deep learning model was developed utilizing EEG signals. Ten-fold cross-validation method was employed to evaluate the model's performance. The dataset was then split into two components： a training set （90%） for LSTM model development and a test set （10%） for validation. The accuracy， recall rate， precision， F1-score， schizophrenia diagnosis and EEG abnormality grading were used as evaluation indicators， and the results of the proposed model were compared to the assessments made by experienced psychiatrists. ResultsFor schizophrenia diagnosis， the modeling group achieved the following performance metrics： precision （94.40±3.03）%， recall rate （94.30±3.23）%， accuracy （94.60±2.22）%， and F1-score （94.20±2.20）%. In the validation group， the corresponding metrics were precision （90.90±2.85）%， recall rate （92.20±1.14）%， accuracy （92.20±1.69）%， and F1-score （91.50±1.78）%. Statistical analysis revealed no significant differences between the LSTM diagnostic model and the experienced psychiatrists in terms of precision， recall rate， accuracy， and F1-score for schizophrenia diagnosis （χ²=1.500， 0.750， 2.722， 1.056， P>0.05）. The modeling group demonstrated an accuracy rate of （91.71±1.73）% in grading EEG abnormalities. For Grade 1 abnormalities， the modeling group reported a precision of （96.40±2.39）%， a recall rate of （94.77±1.40）%， and an F1-score of （95.55±1.14）%. In the case of Grade 2 abnormalities， the precision was （85.89±2.04）%， the recall rate was （88.10±6.18）%， and the F1-score was （87.06±3.12）%. For the more severe Grade 3 abnormalities， the modeling group's precision was （79.61±7.33）%， the recall rate was （81.79±9.87）%， and the F1-score was （80.41±6.79）%. Additionally， the validation group exhibited an accuracy rate of （85.61±6.16）%. The precision， recall rate， and F1-score for Grade 1 abnormalities were （91.43±6.25）%， （92.64±9.65）% and （91.56±4.83）%， respectively. For Grade 2 abnormalities， these metrics were （71.17±19.02）%， （77.64±17.24）% and （71.88±11.33）%. In the case of Grade 3 abnormalities， the precision was （90.00±21.08）%， the recall rate was （80.00±25.82）%， and the F1-score was （81.67±19.95）%. There was no significant difference in the accuracy， recall， accuracy and F1 value between LSTM model and senior doctors in evaluating the abnormal degree of EEG in schizophrenia （χ²=0.098， 0.036， 0.020， 0.336， P>0.05）. The LSTM model takes less time to diagnose schizophrenia and EEG abnormalities than senior doctors， and the differences were statistically significant （t=57.147， 43.104， P<0.01）. ConclusionThe study utilizes an EEG-based LSTM deep learning model for diagnosing first-episode schizophrenia and grading EEG abnormalities， and the model not only matches the performance of experienced psychiatrists but also significantly reduces the time required for diagnosis.

Background The effects of meteorological factors and air pollutants on ischemic heart disease (IHD) hospitalizations in Urumqi have not been fully understood. Objective To investigate the effects of meteorological conditions (temperature, relative humidity) and common air pollutants [fine particulate matter (PM_2.5), inhalable particulate matter (PM₁₀), ozone (O₃), sulfur dioxide (SO₂), nitrogen dioxide (NO₂), and carbon monoxide (CO)] on the daily hospitalization volume of IHD, and to provide a scientific basis for the development of targeted prevention and management strategies. Methods Basic information of 90622 IHD hospitalized patients in Urumqi City was collected from January 1, 2014 to December 31, 2022, and daily air pollutant concentration data and meteorological data were collected during the same period. The meteorological data included daily mean temperature, daily maximum temperature, daily minimum temperature, and daily mean relative humidity, and the common air pollutants included PM_2.5, PM₁₀, daily maximum 8-h average concentration of O₃ (O₃_8 h), SO₂, NO₂, and CO. Descriptive statistical analyses (mean, standard deviation, and quartiles) were performed on the collected data. A distribution lag nonlinear model (DLNM) based on time-stratified case-crossover design was established to estimate the lagged effects (RR) as well as the cumulative lagged effects (RR_cum) of daily mean temperature, relative humidity, and different air pollutants on the number of IHD admissions, stratified by gender and age (<60 and ≥60 years). Subsequently, a generalized additive model (GAM) was used to explore the effects of cold waves (≤ P₅ of the daily minimum temperature and lasting ≥3 d) versus heat waves (≥ P₉₅ of the daily maximum temperature and lasting ≥3 d) on IHD hospitalizations and the potential interactions between temperature and the more influential air pollutants [particulate matter (PM) and O₃_8 h] on IHD hospitalizations. Results The maximum number of IHD hospitalizations in a single day in Urumqi from January 1, 2014 to December 31, 2022 was 100, and the average daily number of hospitalized IHD patients was 27. Daily mean temperature, relative humidity, and air pollutants had different nonlinear relationships and hysteresis with IHD hospitalizations. Extremely low temperatures (<P₁: −18 °C) showed the greatest risk to admission for the total IHD population at a cumulative lag of 31 d (lag0-31) (RR_cum=2.092, 95%CI: 1.261,3.471). Female [lag0-31, RR_cum and 95%CI: 3.416 (2.296,5.082)] and people ≥60 years old [lag0-31, RR_cum and 95%CI: 2.356 (1.681,3.303)] were more sensitive to extremely low temperatures. The risk of IHD hospitalization was greatest on lag20 for cold waves (RR=1.242, 95%CI: 1.053, 1.465), and no lagged effect of heat waves on the number of IHD hospitalizations was found. There was a positive interaction (SI >1, P<0.001) between temperature, PM, and O₃_8 h on the risk of IHD hospitalization, especially for low temperature-high PM and O₃_8 h. Conclusion Both low temperature and high pollutant concentrations associate with an increase in IHD hospitalizations with lagged effects in Urumqi from 2014 to 2022, while cold waves associate with a higher risk of IHD admissions. Females and people aged 60 years and older are at high risk.

Compared with the global average, the incidence rate of nasopharyngeal carcinoma (NPC) in China is higher, particularly in the southern regions where the mortality rate has remained persistently high. Nimotuzumab, a targeted therapy that acts on the epidermal growth factor receptor, has prompted continuous progress in NPC treatment. The combination of nimotuzumab with traditional radiotherapy and chemotherapy can enhance treatment efficacy, reduce adverse reactions, and improve patients’ quality of life. This article summarizes current research findings from this perspective to provide diagnostic and therapeutic strategies for NPC treatment.

Objective To observe the effect of a new cell delivery tool(MSC exo)on the proliferation of pancreatic cancer by transferring targeted genes.Methods Transmission Electron Microscope(TEM)and Nanoparticle Tracking Analysis(NTA)were used to identify human mesenchymal stem cell exosomes(MSC-exo)and transport miR-450a-5p into CFPAC-1,to explore the effect of miR-450a-5p targeting BZW2 on inhibiting the proliferation of pancreatic cancer cells.Results The expression of miR-450a-5p was low in pancreatic cancer tissue(P<0.05),and the expression of CD63 and TSG101 of MSC-exo-miR-450a-5p in CFPAC-1 cells was higher than that of MSC-exo by Western blot(P<0.05).CCK-8 and EdU results showed that MSC-exo-miR-450a-5p significantly inhibited the proliferation of CFPAC-1 cells(P<0.05).Cell scratch and Transwell experiments showed that MSC-exo-miR-450a-5p can inhibit the migration and invasion of CFPAC-1 cells(P<0.05).Through dual luciferase assay,it was confirmed that miR-450a-5p targets BZW2,and RT-qPCR and Western blotting showed a negative correlation(P<0.05)between miR-450a-5p and BZW2 expression.Overexpression of BZW2,CCK-8,EdU,cell scratch,and Transwell experiments confirmed that pc-BZW2 reversed the anti-cancer function of MSC-exo-miR-450a-5p on CFPAC-1.Western blot detected PCNA,Ki-67,MMP2,MMP9,and the results were consistent with the above experiments(P<0.05).Conclusion hMSC exo is a new delivery system,targeting BZW2 to transport miR-450a-5p to inhibit the biological malignancy of pancreatic cancer cells,which provides an important clue for the research of targeted treatment of pancreatic cancer.

Objective:To evaluate the relationship between hippocampal receptor-interacting protein kinase-1 (RIPK1) and nucleotide-binding oligomerization domain-like receptor containing pyrin domain 3 (NLRP3) inflammasomes in postoperative neurocognitive dysfunction of aged rats with chronic knee arthritis pain.Methods:Sixty-four healthy male Sprague-Dawley rats, aged 18 months, weighing 500-550 g, were divided into 4 groups ( n=16 each) using a random number table method: chronic knee arthritis pain group (group P), chronic knee arthritis pain+ operation group (group PS), RIPK1 inhibitor necrostatin-1+ chronic knee arthritis pain+ operation group (group NPS), and DMSO+ chronic knee arthritis pain+ operation group (group DPS). The knee arthritis model was prepared by intra-articular injection of monosodium iodoacetate (MIA) 1 mg into the left knee joint, and 12 weeks later exploratory laparotomy was performed under sevoflurane anesthesia. Necrostatin-1 6.25 mg/kg and the equal volume of DMSO were intraperitoneally injected at 1 h before operation in NPS group and DPS group, respectively. Thermal pain threshold was measured at 1 week before MIA injection and 6 and 12 weeks after MIA injection. Morris water maze test was used to evaluate the cognitive function at 7 days after surgery. Hippocampal tissues were obtained for microscopic examination of the pathological changes (after HE staining) and for determination of the expression of RIPK1, phosphorylated RIPK1 (p-RIPK1), NLRP3, activated cysteine-aspartic protease caspase-1 (cl-caspase-1), apoptosis-associated speck-like protein containing a CARD (ASC) (by Western blot) and contents of interleukin-1beta (IL-1β) and IL-18 (by enzyme-linked immunosorbent assay). Results:Thermal pain threshold was significantly decreased at 6 and 12 weeks after MIA injection as compared with that before injection ( P<0.05), and there was no significant difference in thermal pain threshold among the four groups ( P>0.05). Compared with P group, the escape latency was significantly prolonged, the time of staying at the original platform quadrant was shortened, the number of crossing the original platform was reduced, the expression of RIPK1, p-RIPK1, NLRP3, cl-caspase-1 and ASC was up-regulated, and the contents of IL-1β and IL-18 were increased ( P<0.05), and pathological changes of hippocampal neurons were marked in PS group, DPS group and NPS group. Compared with PS group and DPS group, the escape latency was significantly shortened, the time of staying at the original platform quadrant was prolonged, the number of crossing the original platform was increased, the expression of RIPK1, p-RIPK1, NLRP3, cl-caspase-1 and ASC was down-regulated, the contents of IL-1β and IL-18 were decreased ( P<0.05), and pathological changes of hippocampal neurons were significantly attenuated in NPS group. Conclusions:Postoperative hippocampal RIPK1 function is enhanced in aged rats with chronic knee arthritis pain, which then activates NLRP3 inflammasomes, triggering neuroinflammation, and this process may be involved in the mechanism of postoperative neurocognitive dysfunction.

ObjectiveTo compare the effects of different doses and withdrawal time of 4-vinylcyclohexene diepoxide （VCD） on the reproductive endocrine levels of female rats， and to explore the effective， stable， and safe dosage of VCD for constructing a premature ovarian insufficiency （POI） rat model. MethodSD rats with regular estrous cycles were randomly divided into three groups： blank group， low-dose VCD group （80 mg·kg^-1·d^-1）， and high-dose VCD group （160 mg·kg^-1·d^-1）， with 24 rats in each group. After drug intervention， samples were collected on the 15th day （D15） and the 45th day （D45） after intervention. The general condition， rate of estrous cycle disturbance， serum hormone levels， ovarian histomorphology， follicle count， pregnancy outcome， and the protein and mRNA expression of transforming growth factor （TGF）-β and Smad2/3 were assessed. ResultCompared with the blank group， the low-dose VCD group showed no significant differences in the rate of estrous cycle disturbance or serum follicle-stimulating hormone （FSH）， luteinizing hormone （LH）， and estradiol （E₂） levels. Ovarian tissue was damaged. Specifically， the number of primordial and primary follicles decreased on D15 （P<0.01）， and the number of secondary follicles （P<0.01） and antral follicles （P<0.05） further decreased on D45. The litter number decreased on D15 （P<0.05）， but there was no significant difference on D45. Furthermore， TGF-β protein levels increased on D15 （P<0.05） and D45 （P<0.01）. The Smad2/3 levels increased on D45 （P<0.01）， and TGF-β and Smad2/3 mRNA levels increased on D45 （P<0.05）. Compared with the results in the blank group， the disturbance rate of the estrous cycle increased on D45 in the high-dose VCD group （P<0.01）. The serum of FSH and LH increased （P<0.01）， while E₂ decreased （P<0.05）. Ovarian tissue was damaged， and the downward trend of follicles at all levels was similar to that in the low-dose VCD group. The litter number significantly decreased on D15 and D45. TGF-β and Smad2/3 protein levels increased （P<0.05，P<0.01）， and TGF-β mRNA increased on D45 （P<0.05）. ConclusionHigh-dose VCD is an ideal method for constructing a POI rat model， being effective， stable， and safe.

Background and objective Small cell lung cancer(SCLC)is known as recalcitrant cancer with high malignancy and heterogeneity.Immunotherapy has changed the treatment pattern of extensive-disease SCLC(ED-SCLC),but the beneficiary population is limited.Therefore,exploring new therapeutic strategies is an urgent clinical problem to be solved for SCLC.SCLC is characterized by highly active glycolytic metabolism and pyruvate kinase Ml(PKM1)is one of the isozymes of PK,an important rate-limiting enzyme in glycolysis pathway.Previous studies have shown that PKM1 is related to autophagy and drug sensitivity,however,how PKM1 regulates drug sensitivity in SCLC and its mechanism remain unclear.The aim of this study was to investigate the biological functions of PKM1 in SCLC,including its effects on proliferation,migra-tion,autophagy,drug sensitivity,and expression of neuroendocrine(NE)-related markers in SCLC.Methods Western blot was used to detect the expression level of PKM1 in SCLC cells.PKM1 gene-overexpressed SCLC cell lines were constructed by stable lentivirus transfection.Proliferation of cells and drug sensitivity were detected by MTT,and migration ability of cells was determined by Transwell.The level of autophagy was detected by flow cytometry.Western blot was used to determine the expression levels of NE-related proteins.Results PKM1 was differentially expressed among various SCLC cell lines,and was lower in H1092 cells(P＜0.01).Compared with the control group,there was no significant difference in proliferation level of PKM1 overexpressing H1092 cell,but the migration ability was significantly increased(P＜0.001),the drug sensitivity was re-duced,and the level of autophagy was inhibited(P＜0.001).Additionally,overexpression of PKM1 could upregulate the expres-sion of non-neuroendocrine(non-NE)-related proteins(P＜0.01)and decrease the expression of NE-related proteins(P＜0.01).Conclusion PKM1 was differentially expressed in SCLC cell lines,and high expression of PKM1 did not affect the prolifera-tion,but affected the migration of SCLC cells.PKM1 might affect drug sensitivity by inhibiting autophagy and regulating the expression of NE markers.These results provide a theoretical basis for exploring the role of PKM1 in SCLC.