Perimenopause raises the risk and incidence of depression, whereas the underlying molecular mechanism remains unclear. Disturbed glucose regulation has been widely documented in depressive disorders, which renders the brain susceptible to various stresses such as estrogen depletion. However, whether and how glucose dysfunction regulates depression-like behaviors and neuronal damage in perimenopausal transition remains unexplored. Here, a prominent depressive phenotype was found in perimenopausal mice induced by the ovarian toxin 4-vinylcyclohexene diepoxide (VCD). The VCD depression susceptible group (VCD^SS) and the VCD depression resilient group (VCD^RES) were determined using a ROC-based behavioral screening approach. We found that the hippocampus, a crucial region linked to depression, had hyperglycemia and mitochondrial abnormalities. Interestingly, oral administration of the SGLT2 inhibitor empagliflozin (EMPA) and intrahippocampal glucose infusion suggest a close relationship between hyperglycemia in the hippocampus and the susceptibility to depression. We verified that cytochrome c oxidase 7c (COX7C) downregulation is a potential cause of the high glucose-induced neuronal injury using proteomic screening and biochemical validations. High glucose causes COX7C to be ubiquitinated in a S-phase kinase associated protein 1 (SKP1)-dependent manner. According to these results, SKP1/COX7C represents a unique therapeutic target and a novel molecular route for treating perimenopausal depression.

Objective : To predict and validate key targets for cisplatin(DDP) resistance in colorectal cancer(CRC) to provide more options for precision medicine in clinical treatment. Methods: Differentially expressed genes(DEGs) between normal colonic mucosa and CRC were screened from the gene expression omnibus(GEO) database. Key genes were identified using the STRING database and Cytoscape software. DEGs were subjected to enrichment analysis using the gene ontology(GO) and kyoto encyclopedia of genes and genomes(KEGG) databases. Key targets were validated through RNA-seq, qRT-PCR, and Western blot. The versican(VCAN) gene overexpression vector was transfected into human ileocecal colorectal adenocarcinoma cell line HCT8, and cell viability was assessed using the CCK-8 assay. Flow cytometry was used to assess apoptosis and cell cycle distribution. qRT-PCR and Western blot were performed to detect mRNA and protein levels of the target genes. Results : In this study, 118 upregulated DEGs and 146 downregulated DEGs were identified from the GEO database. DEGs were mainly enriched in extracellular matrix degradation, extracellular matrix organization, and the phosphoinositide 3-kinase(PI3K)-protein kinase B(AKT) signaling pathway. Based on protein-protein interaction network analysis, 20 hub genes were identified. By comparing the transcriptome sequencing results of the HCT8 parental strain and DDP-resistant strain, the VCAN gene was further selected. In CRC tissues, the expression level of VCAN was higher than that in normal colonic mucosa, and patients with high VCAN expression had shorter overall survival(OS) and recurrence free survival(RFS) times. Overexpression of VCAN in CRC cells promoted cell proliferation(P<0.05), increased resistance to DDP, reduced DDP-induced apoptosis(P<0.05), and G0/G1phase arrest(P<0.05); upregulation of VCAN activated the protein kinase B(AKT)-mammalian target of rapamycin(mTOR) signaling pathway. Conclusion Bioinformatics and transcriptome sequencing identified VCAN as a key target gene for DDP resistance in CRC, potentially promoting CRC progression and DDP resistance by regulating the AKT-mTOR pathway.

Background and purpose:The incidence of autonomic dysfunction(AD)in patients with advanced cancer is approximately 65%-80%.The neurasthenic symptoms such as dizziness,palpitations and fatigue caused by AD are difficult to alleviate even with sufficient rest,seriously affecting the patients'quality of life.Meanwhile,the cardiovascular autonomic nervous system plays a significant regulatory role in heart rate,myocardial function and myocardial blood flow.AD increases the morbidity and mortality risk of cardiovascular diseases in patients.AD is not only a functional state but might also be an early sign of overall myocardial lesion.Research indicates that after adjusting for age,gender and cardiovascular risk factors,previous radiation exposure is associated with AD manifestations such as increased resting heart rate and abnormal heart rate recovery after exercise.However,there are currently few relevant studies on the effect of radiotherapy on cardiac autonomic function,and the specific injury effects and dose threshold of injury occurrence remain unclear.This study aimed to explore the impact of thoracic radiotherapy on the cardiac autonomic function of patients with malignant tumors by comparing the differences in heart rate variability(HRV)analysis parameters before and after radiotherapy,and to explore the dosimetric risk factors for the occurrence of AD by comparing the dosimetry between the case group and the control group,providing a theoretical basis for optimizing the dose distribution of radiotherapy regimens in order to improve patient prognosis and reduce the occurrence of complications.Methods:We prospectively collected data of patients with malignant tumors who underwent thoracic radiotherapy in the Radiotherapy Department of the Affiliated Hospital of North China University of Science and Technology from February 2023 to December 2023.Inclusion criteria:① Patients who were pathologically confirmed to have malignant tumors(lung cancer breast cancer or esophageal cancer);② patients with radiation therapy indications as recommended by the guidelines;③ patients with an ECOG score of 0-1;④ patients with no significant abnormalities in electrocardiogram and echocardiography results.Exclusion criteria:① previously received chest radiotherapy;② patients with obvious palpitation,chest tightness and chest pain before treatment;③ diabetes,heart disease and other serious underlying diseases;④ anti-arrhythmic drugs are currently being used;⑤ patients who cannot tolerate radiotherapy and who were lost or lost during follow-up.HRV analysis was used to evaluate changes in autonomic nerve function after radiotherapy.Patients with AD were included in the case group,and the remaining patients were included in the control group.Univariate and multivariate logistic regression analysis methods were used to explore the dosimetric risk factors and cardiac dose limitations for the occurrence of AD after thoracic radiotherapy.This study was approved by the ethics committee of Affiliated Hospital of North China University of Science and Technology(ethics number:20230228020).Results:A total of 89 patients with thoracic tumors meeting the study criteria were enrolled in the study.Among them,41(46%)patients experienced cardiac AD after radiotherapy.The cardiac Dmax(6 273.500 cGy vs 4 675.900 cGy,P＜0.001),cardiac Dmean(1513.700 cGy vs 452.050 cGy,P＜0.001),cardiac V5(49.000%vs 21.250%,P＜0.001),V20(30.500%vs 7.300%,P＜0.001),V30(18.700%vs 3.600%,P＜0.001)and V40(10.900%vs 1.500%,P＜0.001)were significantly higher in the case group than in the control group.The results of multivariate logistic regression analysis showed that cardiac V30 was an independent risk factor for the occurrence of cardiac AD[OR(95%CI)=1.583(1.093-2.291),P=0.015].Cardiac V30 could predict the occurrence of radiation-induced cardiac injury with an area under the curve of 0.788,and 17.1%was the optimal cut-offvalue of cardiac V30 for predicting the occurrence of cardiac AD.Conclusion:After thoracic radiotherapy,the cardiac irradiation dose-volume was significantly higher in patients with cardiac AD than in the control group.When cardiac V30 was higher than 17.1%,the risk of cardiac AD in patients significantly increased.

Objective:To discuss the synergistic inhibitory effect of apatinib mesylate(apatinib)combined with radiotherapy(RT)on the hepatocellular carcinoma(HepG2)cells in vitro,and to clarify its related antitumor mechanism.Methods:The HepG2 cells were cultured in vitro and treated with different concentrations of apatinib and/or varying doses of X-rays.MTT method was used to detect the survival rates of the cells in various groups;the inhibitory rates of cell proliferation and the 20％inhibitory concentration(IC20)of apatinib were calculated;the X-ray irradiation dose for subsequent experiments was detected.The HepG2 cells were divided into apatinib group,RT group,and apatinib+RT group(combined group).Flow cytometry was used to detect the apoptotic rates of the cells in various groups;wound healing assay was used to detect the migration rates of the cells in various groups;ELISA method was used to detect the levels of vascular endothelial growth factor(VEGF)in the cell culture supernatant in various groups.Results:The MTT results showed that the IC20 of apatinib was 1.32 μmol·L-1,and this concentration was used for subsequent experiments,and the X-ray irradiation dose for the follow-up experiments was 2 Gy.Compared with control group,the apoptotic rates of the cells in apatinib group and RT group had no significant differences(P＞0.05),while the apoptotic rate of the cells in combined group was increased(P＜0.05).Compared with control group,the migration rates of the cells in apatinib group,RT group,and combined group were decreased(P＜0.05);compared with apatinib group and RT group,the migration rate of the cells in combined group was decreased(P＜0.05).Compared with control group,the levels of VEGF in the cell culture supernatant in apatinib group and combined group were decreased(P＜0.05);compared with apatinib and RT group,the level of VEGF in the cell culture supernatant in combined group was decreased(P＜0.05).Conclusion:Apatinib combined with radiotherapy significantly inhibits the proliferation and migration of the HepG2 cells in vitro and induces the apoptosis;its effect may be related to the inhibition of VEGF secretion by cells.

Objective To explore the changes of fatigue status before and after radiotherapy in tumor patients and its influencing factors.Methods A total of 150 tumor patients with radiotherapy in the radiother-apy department of this hospital from February to September 2023 were selected as the study subjects.The general data questionnaire and the Multidimensional Fatigue Scale (MFI-20) were adopted to conduct the sur-vey.The fatigue scores and the changes in autonomic nervous function were compared between before and af-ter radiotherapy.The multifactor logistic regression was applied to analyze the influencing factors of changes in fatigue status.Results Compared with before radiotherapy,the average fatigue scores after radiotherapy were higher[(63.99±14.54)points vs. (52.75±17.18)points],low frequency (LF),and high frequency (HF),total power (TP),time domain indicators sinus heart beat RR interval standard deviation (SDNN) and the root-mean-square value of the difference between adjacent NN interval (rMSSD) were lower,LF/HF was higher,and the differences were statistically significant (P<0.05).The univariate analysis results showed that the fatigue situation had statistical difference among the patients with different clinical stages,chronic dis-ease history,pain scores,hemoglobin,lymphocyte,WBC and heart rate variability (HRV,P<0.05).The mul-tivariate logistic regression analysis results showed that the decrease of hemoglobin,WBC and HRV were the independent risk factors of fatigue aggravation (P<0.05).Conclusion It is necessary to guide the clinic to conduct the intervention on the influencing factors aggravating fatigue to improve the outcome of the patients with tumor.

Objective:To ulteriorly explore the differences of psychotic symptoms and neurocognitive between patients with first-episode deficit subtype of schizophrenia (FDS) and patients with first-episode nondeficit subtype of schizophrenia (FNDS).Methods:From January 2021 to September 2021, a total of 88 first-episode treatment-naive schizophrenia were recruited from the Mental Health Center of West China Hospital and divided into FDS group( n=44) and FNDS group( n=44) according to the schedule for the deficit syndrome (SDS), and 44 healthy subjects were included as healthy control group (HC group, n=44). Positive and negative syndrome scale (PANSS) was used to assess psychotic symptoms of patients and Wechsler adult intelligence scale, trail making test and logic memory test were used to evaluate intelligence quotient and neurocognitive function of all subjects.SPSS 22.0 was used for statistical analysis, and independent samples t-test and one-way analysis of variance (ANOVA) were used to compare variables that met normal distribution, while the Mann-Whitney U test and Kruskal-Wallis H test were used to compare variables that did not meet normal distribution. Results:(1) There were significant differences in psychotic symptoms between the FDS group and the FNDS group.Compared with the FNDS group, the FDS group had higher total score of PANSS ((95.95±16.82) vs (88.39±16.29)), negative symptoms ((27.57±7.52) vs (16.57±5.76)) and anergastic reaction ((13.43±3.82) vs (7.00(5.00, 9.00)), and lower positive symptoms scores ((21.95±6.88) vs (25.41±6.07)), activation ((8.00(5.00, 9.00) vs (9.27±3.47)), depression ((5.50(4.00, 9.00) vs (8.00(6.00, 12.00)) and supplementary item ((13.60±4.17) vs (17.30±5.39))(all P<0.05). (2) There were differences in neurocognitive functions between FDS group and FNDS group, and which in FDS and FNDS group were worse than that in HC group.Spatial memory (block design test: (23.70±11.05) vs (31.72±11.49)) and information processing speed (digit symbol test: (38.38±15.85) vs (47.97±14.99)) of FDS group were significantly lower than those of FNDS group(both P<0.05). Intelligence quotient, information processing speed and spatial memory of FDS group and FNDS group were lower than those of HC group(all P<0.05). Conclusion:FDS patients has more severe negative symptoms and anergastic reaction, and exit worse information processing speed and spatial memory dysfunction than FNDS patients.This unique pattern of impairment suggests that information processing speed and spatial memory may be important classification indicators for differentiating the deficit subtype of schizophrenia in the early stage.

Alzheimer disease (AD) is the most common cause of dementia, and its early diagnosis is of great importance to delay the disease and improve the prognosis. Compared with cerebrospinal fluid, blood tests have the advantages of being less invasive and easier to obtain. In recent years, with the application of ultrasensitive detection technology, the diagnostic value of blood markers for AD has been continuously explored, which is expected to provide more direct and effective evidence for early diagnosis and early intervention of AD.

Ferroptosis is a type of cell death accompanied by iron-dependent lipid peroxidation, thus stimulating ferroptosis may be a potential strategy for treating gastric cancer, therapeutic agents against which are urgently required. Jiyuan oridonin A (JDA) is a natural compound isolated from Jiyuan

Objective:To explore the effect of enhanced recovery nursing pathway in the enhanced recovery after surgery of perioperative patients with hepatic echinococcosis.Methods:From November 2017 to February 2019, simple random sampling was used to select 160 hepatic echinococcosis patients with surgery admitted to Shannan People's Hospital of Tibet Autonomous Region as the research object. Patients were randomly divided into experimental group and control group, 80 cases in each group. Patients in control group received general surgical routine nursing, and experimental group carried out enhanced recovery nursing pathway on the basis of routine nursing. The postoperative rehabilitation indicators, pain scores and postoperative complications were compared between the two groups.Results:The time of first exhaust time and defecation in experimental group was (3.77±3.05) h and (23.81±17.29) h, which was earlier than (13.27±8.58) h and (37.79±18.23) h in control group, and the differences were statistically significant ( t=4.265, 4.975; P<0.01) . The pain scores of experimental group at 2, 4, 8, and 24 hours after surgery were (1.08±1.04) , (1.61±0.85) , (1.13±0.70) and (0.26±0.41) lower than those [ (2.41±1.20) , (2.94±0.96) , (2.94±0.96) , (1.33±0.90) ]of control group, and the differences were statistically significant ( t=7.501, 9.250, 13.650, -8.720; P<0.01) . There were 2 cases (2.50%) of lung infection in experimental group and 13 cases (16.25%) in control group. The incidence in experimental group was lower than that in control group, and the difference was statistically significant (χ 2=8.901, P<0.01) . Conclusions:The standardized nursing model based on the enhanced recovery nursing pathway is conducive to the postoperative rehabilitation of patients with hepatic echinococcosis, shortens the hospital stay, and reduces postoperative lung infection complications, which is worthy of further promotion.

OBJECTIVES: To evaluate curative effects of coronavirus disease 2019 (COVID-19) patients by the transfusion of other convalescent plasma. METHODS: Retrospective analysis of the clinical data of 18 patients with severe and critical COVID-19, who were hospitalized in the ICU of Xianghu Branch of the First Affiliated Hospital of Nanchang University from February 1 to March 15, 2020. Patients were subdivided into an experimental group (=6, who had transfused the plasma) and an observation group (=12, who had no plasma transfusion). Basic clinical data and prognosis indexes of these two groups were compared. Moreover, for the experimental group, the dynamic changes of blood oxygen saturation before and after the transfusion, the changes of lymphocyte absolute value 48 hours after the transfusion, and the detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) nucleic acid were analyzed. RESULTS: There were no significant differences in age, gender, blood type and other basic clinical data between the two groups (all >0.05).There were no significant differences in ventilator machine weaning time, extracorporeal membrane oxygenation (ECMO) weaning time, body temperature recovery to normal time, and hospitalization days between these two groups (all >0.05). For the experimental group, before, during and after the convalescent plasma transfusion, the blood oxygen saturation of all 6 patients at all time (1, 6, 8, 12, 24, 36, and 48 h) was more than 90%, and there was no significant fluctuation. There were 3 patients whose absolute value of lymphocyte was increased 48 hours after the transfusion, and the remaining was decreased. There were 5 patients whose SARS-CoV-2 nucleic acid detection turned negative 48 hours after the transfusion, accounting for 83.3%. CONCLUSIONS Transfusion of convalescent plasma will not affect outcomesof COVID-19 patients, which can neutralize SARS-CoV-2 in patients and reduce the loading capacity of SARS-CoV-2.
Betacoronavirus ; Blood Component Transfusion ; China ; Coronavirus Infections ; therapy ; Humans ; Immunization, Passive ; Pandemics ; Plasma ; Pneumonia, Viral ; therapy ; Retrospective Studies