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 The aim of the study was to investigate and analyze the resource allocation and surveillance status of hospital-associated infections in secondary and above healthcare facilities in Anhui province.METHODS Secondary and above healthcare institutions in 16 cities were selected in Mar.2023 by convenient sampling meth-od,and self-designed questionnaire was administered by'wenjuanxing'to investigate the characteristics of health-care facilities,the management and surveillance of hospital-acquired infections.RESULTS A total of 302 medical facilities,including 88 tertiary and 195 comprehensive facilities,completed the survey.All tertiary healthcare fa-cilities set up the independent departments for hospital-associated infections,while 12.15%of secondary health-care facilities did not.Totally 17.22%of healthcare facilities did not meet the standard requirements of ratio of full-time equivalents to beds,while the unqualified rate of tertiary healthcare facilities(25.00%)was higher than that of secondary healthcare facilities(14.02%).The full-time equivalents were mainly in nursing(64.89%),and relatively insufficient in other specialties.All tertiary healthcare facilities had carried out comprehensive surveil-lance,however,secondary healthcare facilities still needed to be improved.The allocation ratio of surveillance in-formation for system hospital-associated infection was 37.42%in tertiary healthcare facilities,but only 18.69%in secondary.CONCLUSIONS The hospital-associated infection management system of certain healthcare facilities in Anhui province still calls for improving,more personnel numbers and specialties are required.Besides,the con-struction of information system urgently needs to be strengthened.At the same time,more attention should be paid to secondary healthcare facilities,which should be supplied for more resources,carry out basic monitoring work to reduce hospital-associated infections and ensure patients'safety.

OBJECTIVE To evaluate the changes in monitoring indicators related to healthcare-associated infections(HAIs)management in Anhui Province in 2018 and 2022,to provide a scientific basis for optimizing HAI control strategies.METHODS A cross-sectional survey was conducted in 2019 and 2023 across 48 secondary and tertia-ry medical institutions,HAI data were collected and analyzed.RESULTS The two-year averages of monitoring indi-cators were as follows:the incidence rate of HAIs was 0.66％,the prevalence rate of HAIs was 1.69％,the inci-dence rate of surgical site infection for class I incisions was 0.20％,the antibiotic usage rate was 44.59％,the pathogen detection rate for therapeutic antibiotics was 43.76％,the incidence rate of catheter-related blood-stream infection(CRBSI)was 0.64‰,the incidence rate of ventilator-associated pneumonia(VAP)was 5.81‰,and the incidence rate of catheter-associated urinary tract infection(CAUTI)was 0.79‰.By 2022,significant im-provements were observed in most indicators(P＜0.05).Compared to tertiary hospitals,secondary hospitals ex-hibited low rates of hospital infection incidence,prevalence,class I incision infections,antibiotic utilization and CRBSI,but high rates of VAP and CAUTI(P＜0.05).CONCLUSIONS Significant improvements have been made in monitoring indicators related to HAI managements in Anhui Province.However,secondary hospitals still need to enhance their capabilities of monitoring indicators and detecting pathogens.

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.

Objective To evaluate the effectiveness of active screening in improving the detection rate of carbape-nem-resistant Enterobacterales(CRE)in the intensive care units(ICUs).Methods From July 2023 to June 2024,active screening of rectal swab CRE was conducted on ICU patients in 10 hospitals.ICU patients who underwent ac-tive screening from July 2023 to June 2024 were selected as the study group,while those who did not undergo active screening from July 2022 to June 2023 were selected as the control group.Difference in CRE detection rates between the two groups of patients was compared.Results A total of 7 803 ICU patients were included in the study group,744 CRE strains were detected,with a detection rate of 9.53％,out of which 304 CRE strains were detected through routine detection(detection rate 3.90％),3 707 patients underwent active screen,440 CRE strains were detected(detection rate 11.87％).7 561 ICU patients were included in the control group,out of which 250 CRE strains were detected through routine detection,with a detection rate of 3.31％.There was a statistically significant difference in the overall detection rate of CRE between two groups of patients(x2=246.18,P＜0.001).In the study group,CRE detection rate of active screening(11.87％)was higher than that of routine detection(3.90％),with statistically significant difference(x2=264.26,P＜0.001).A total of 17 CRE strains were detected from the study group.The proportions of Klebsiella pneumoniae(80.92％vs 73.41％)and Serratia marcescens(2.30％vs0.23％)in the routine detection group were both higher than in the active screening group,while the proportion of Escherichia coli in the routine detection group was lower(8.22％vs 19.55％),all with statistically significant differences(all P＜0.05).Conclusion The prevalence of CRE in ICUs is relatively high,with a wide range of bac-terial species.Active screening can improve the detection rate of CRE.

Objective:To explore the impact of the two-way referral model on compliance and prognosis in patients with heart failure.Methods:This bidirectional cohort study enrolled chronic heart failure (CHF) patients treated at Qilu Hospital of Shandong University or designated primary hospitals between March 2018 and March 2022. Patients were categorized into two groups based on referral status: two-way referral group (participating in the referral model with≥1 follow-up visit at primary hospitals) and the core hospital group (receiving treatment and follow-up exclusively at Qilu Hospital). Baseline clinical characteristics were collected and compared between groups. Patients underwent followed-up, with primary endpoints including follow-up rate, drug (β-blockers, angiotension converting enzyme inhibitor (ACEI)/angiotensin Ⅱ receptor blockers (ARB)/angiotensin receptor-neprilysin inhibitor (ARNI), sodium-glucose cotransporter 2 inhibitors and mineralocorticoid receptor antagonists) utilization rate and target dose achievement rate. Secondary endpoints encompassed changes from baseline in left ventricular ejection fraction (LVEF), left ventricular end-diastolic diameter (LVEDd), and N-terminal pro-brain natriuretic peptide (NT-proBNP), plus cardiovascular mortality and heart failure rehospitalization. Generalized linear mixed models analyzed longitudinal trends in LVEF, LVEDd, and NT-proBNP levels. Kaplan-Meier curves and Cox regression evaluated LVEF recovery rates, supplemented by subgroup analyses. Multivariate logistic regression was used to identify factors influencing target dose achievement rate for β-blockers and ACEI/ARB/ARNI therapies in CHF patients.Results:A total of 357 patients were enrolled, aged 53 (41, 63) years, including 256 males (71.7%). 157 patients were in the two-way referral group and 200 patients in the core hospital-treated group. Compared with the core hospital-treated group, the two-way referral group had lower baseline LVEF (28 (22, 34)% vs. 31 (23, 36)%, P=0.021) and systolic blood pressure (116 (104, 125) mmHg vs. 121 (109, 134) mmHg (1 mmHg=0.133 kPa), P=0.010). The 12-month follow-up rate of the two-way referral group was higher than the core hospital-treated group (73.8% vs. 56.0%, P=0.004). No significant between-group differences were observed in drug utilization rate of β-blockers, ACEI/ARB/ARNI, or sodium-glucose cotransporter 2 inhibitors during follow-up (all P>0.05), while mineralocorticoid receptor antagonists use showed a declining trend in both groups. Although the core hospital-treated group had higher target dose achievement rates for β-blockers (65.4% vs. 49.3%, P=0.042) and ACEI/ARB/ARNI (79.8% vs. 65.8%, P=0.046) than the two-way referral group, multivariate logistic regression indicated that the two-way referral model was not a negative predictor for these outcomes (all P>0.05). Both groups showed improved NT-proBNP, LVEDd, and LVEF from baseline (all P<0.001) with no significant difference in trends between groups (all P>0.05). There was no significant difference in the composite incidence (7.6% vs. 6.5%, P=0.674) and cumulative incidence (log-rank P=0.684) of cardiovascular death and heart failure rehospitalization at 12 months between two groups. Conclusion:The two-way referral model demonstrates advantages in improving medication adherence, drug utilization rates, and targetdoseachievement rates among CHF patients. This model not only promotes cardiac functional recovery but also reduces risks of cardiovascular mortality and heart failure rehospitalization, achieving comparable therapeutic and management outcomes to those observed in core hospital-treated patients.

Objective:To explore the clinical characteristics and risk factors for the progression of severe scrub typhus in children.Methods:Clinical data, laboratory and auxiliary examination results, treatment and prognosis data of children with scrub typhus admitted to Xiamen Children's Hospital from July 2014 to March 2024 were collected. The clinical characteristics of scrub typhus in children were analyzed, and the study subjects were divided into severe group and mild group according to their condition. The relevant risk factors for progression to severe cases were analyzed.Results:A total of 42 cases were included, with 34 cases (80.95%) in the mild group and 8 cases (19.05%) in the severe group. All patients(100%) had fever, with the highest incidence of eschar or ulceration (95.24%), followed by lymphadenopathy and splenomegaly. All 42 patients improved or recovered after treatment with azithromycin or doxycycline, with no deaths reported. Compared with the mild group，the severe group had a higher incidence of cough, lymphadenopathy，and hepatomegaly, with statistically significant differences( P<0.05). Compared with the mild group, the severe group showed a decrease in hemoglobin(Hb), platelet, and fibrinogen(Fib) levels, while serum C-reactive protein(CRP), procalcitonin, aspartate aminotransferase, creatine kinase MB, and lactate dehydrogenase (LDH) levels increased, with statistically significant differences( P<0.05). Multivariate Tobit model analysis showed that a decrease in Hb ( OR -0.006，95% CI -0.012-0.000， P<0.05), an increase in CRP ( OR 2.72，95% CI 0.001-0.008， P=0.010), an increase in LDH ( OR 1.76，95% CI 0.000-0.000， P=0.027), and a decrease in Fib ( OR -3.78，95% CI -0.309-0.093， P=0.001) were risk factors for scrub typhus progressing to severe cases. Conclusion:During the epidemic season of scrub typhus, fever accompanied by eschar or ulceration, along with splenomegaly and lymphadenopath aids in the diagnosis of scrub typhus. Decreased Hb and Fib, as well as elevated CRP and LDH, are risk factors for the development of severe scrub typhus in children.

Objective To evaluate the effectiveness of active screening in improving the detection rate of carbape-nem-resistant Enterobacterales(CRE)in the intensive care units(ICUs).Methods From July 2023 to June 2024,active screening of rectal swab CRE was conducted on ICU patients in 10 hospitals.ICU patients who underwent ac-tive screening from July 2023 to June 2024 were selected as the study group,while those who did not undergo active screening from July 2022 to June 2023 were selected as the control group.Difference in CRE detection rates between the two groups of patients was compared.Results A total of 7 803 ICU patients were included in the study group,744 CRE strains were detected,with a detection rate of 9.53％,out of which 304 CRE strains were detected through routine detection(detection rate 3.90％),3 707 patients underwent active screen,440 CRE strains were detected(detection rate 11.87％).7 561 ICU patients were included in the control group,out of which 250 CRE strains were detected through routine detection,with a detection rate of 3.31％.There was a statistically significant difference in the overall detection rate of CRE between two groups of patients(x2=246.18,P＜0.001).In the study group,CRE detection rate of active screening(11.87％)was higher than that of routine detection(3.90％),with statistically significant difference(x2=264.26,P＜0.001).A total of 17 CRE strains were detected from the study group.The proportions of Klebsiella pneumoniae(80.92％vs 73.41％)and Serratia marcescens(2.30％vs0.23％)in the routine detection group were both higher than in the active screening group,while the proportion of Escherichia coli in the routine detection group was lower(8.22％vs 19.55％),all with statistically significant differences(all P＜0.05).Conclusion The prevalence of CRE in ICUs is relatively high,with a wide range of bac-terial species.Active screening can improve the detection rate of CRE.

Objective:To compare the influence of definition methods of different isocenter on postoperative volumetric modulated arc therapy (VMAT) plans for patients with high-grade glioma (HGG),and to explore the feasibility of determining the treatment isocenter at location stage of computed tomography (CT) simulation system (CT-Sim). Methods:A total of 30 HGG patients who received radiotherapy after surgery in Peking University International Hospital from September 1,2021 to December 31,2022 were selected. 4 kinds of methods,which included center of mass (CT-COM) of target region of tumor bed was delineated by CT-Sim location stage,geometric center of target region of treatment plan system (TPS-Geo),whole brain geometric center of treatment plan system (TPS-Head) and center of mass of target region of TPS (TPS-COM),were respectively adopted to definite treatment isocenter for each patient,and they were respectively set as CT-COM group,TPS-Geo group,TPS-Head group and TPS-COM group to design 4 groups of VMAT treatment. The parameters included dose,conformity index (CI),uniformity index (HI) and machine unite (MU) among 4 groups of target region and organ at risk (OAR) were compared. Results:The doses of target region and OAR of four groups were similar,and all of them can meet the requirements of clinical dosimetry and clinical OAR dose limitation,without statistically significant differences (P>0.05). The covered volumes that brain tissues received 10,20,30,40 and 50 Gy doses in CT-COM group,TPS-Geo group and TPS-COM group closed to the maximum dose,the maximum dose of 2％ volume and mean dose (Dmax,D2％,Dmean) of brainstem,bilateral lens,optic chiasm,bilateral optic nerve and pituitary gland. The V10,V20,V30 of brain tissue,and Dmax,D2％,and Dmean of brainstem in TPS-Head group were slightly higher than those in other three groups,and the Dmean of lens,and Dmax,D2％ and Dmean of optic nerve at health side of TPS-Head group were slightly lower than those of other three groups,without statistically significant differences (P>0.05). Conclusion:The four VMAT plans of defining the treatment isocenter can meet the clinical dosimetric requirements,and can determine the isocenter at CT-Sim location stage,which can effectively avoid the occurrence of errors in the reduction of radiotherapy,and increase precision of delivery of radiotherapy dose,and enhance effective utilization rate of equipment.

Objective:To compare the influence of definition methods of different isocenter on postoperative volumetric modulated arc therapy (VMAT) plans for patients with high-grade glioma (HGG),and to explore the feasibility of determining the treatment isocenter at location stage of computed tomography (CT) simulation system (CT-Sim). Methods:A total of 30 HGG patients who received radiotherapy after surgery in Peking University International Hospital from September 1,2021 to December 31,2022 were selected. 4 kinds of methods,which included center of mass (CT-COM) of target region of tumor bed was delineated by CT-Sim location stage,geometric center of target region of treatment plan system (TPS-Geo),whole brain geometric center of treatment plan system (TPS-Head) and center of mass of target region of TPS (TPS-COM),were respectively adopted to definite treatment isocenter for each patient,and they were respectively set as CT-COM group,TPS-Geo group,TPS-Head group and TPS-COM group to design 4 groups of VMAT treatment. The parameters included dose,conformity index (CI),uniformity index (HI) and machine unite (MU) among 4 groups of target region and organ at risk (OAR) were compared. Results:The doses of target region and OAR of four groups were similar,and all of them can meet the requirements of clinical dosimetry and clinical OAR dose limitation,without statistically significant differences (P>0.05). The covered volumes that brain tissues received 10,20,30,40 and 50 Gy doses in CT-COM group,TPS-Geo group and TPS-COM group closed to the maximum dose,the maximum dose of 2％ volume and mean dose (Dmax,D2％,Dmean) of brainstem,bilateral lens,optic chiasm,bilateral optic nerve and pituitary gland. The V10,V20,V30 of brain tissue,and Dmax,D2％,and Dmean of brainstem in TPS-Head group were slightly higher than those in other three groups,and the Dmean of lens,and Dmax,D2％ and Dmean of optic nerve at health side of TPS-Head group were slightly lower than those of other three groups,without statistically significant differences (P>0.05). Conclusion:The four VMAT plans of defining the treatment isocenter can meet the clinical dosimetric requirements,and can determine the isocenter at CT-Sim location stage,which can effectively avoid the occurrence of errors in the reduction of radiotherapy,and increase precision of delivery of radiotherapy dose,and enhance effective utilization rate of equipment.