Objective:To explore the expression of transmembrane protein 9(TMEM9)as an oncogene in prostate cancer(PCa),and to examine its effect on the proliferation and invasion of PCa cells as well as on the Wnt/β-catenin signaling pathway and autophagy of PCa cells by intervening with its expression.Methods:The Cancer Genome Atlas was used for pan-cancer analysis of TMEM9 expres-sion levels in different tumors,and TMEM9 protein and messenger ribonucleic acid(mRNA)levels in clinical PCa and prostatic hyper-plasia specimens were analyzed.Real-time quantitative polymerase chain reaction and western blotting were used to analyze TMEM9 expression levels in different PCa cell lines.Cell counting,terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling(TUNEL),and Transwell assay were used to analyze cell proliferation,apoptosis,and PCa cell invasion,respectively.Subcutaneous tu-morigenesis in nude mice was used to analyze tumor proliferation in vivo.Western blotting was used to analyze the expression of autophagy-related pathway proteins,and transmission electron microscopy and immunofluorescence colocalization were used to deter-mine the colocalization of autophagosomes and lysosomes.Results:TMEM9 was highly expressed in PCa.The mRNA and protein ex-pression levels of TMEM9 were higher in PCa tissues than in prostatic hyperplasia tissues.The expression of TMEM9 was highest in PC3 cells(human PCa cells)(t=17.150,P<0.01).In TMEM9-knocked down PC3 cells,the proliferation(t=3.165,P<0.05)and inva-sion(F=76.620,P<0.01)significantly decreased,and apoptosis(t=13.530,P=0.010)significantly increased.After knockdown of TMEM9,the volume(F=1 699.000,P<0.01)and weight(t=9.057,P<0.01)of subcutaneous tumors in nude mice were reduced,and tu-mor growth was inhibited.TMEM9 regulated the Wnt/β-catenin signaling pathway and inhibited the AKT-mTOR signaling pathway to promote autophagy in PCa cells.Conclusion:TMEM9 inhibits the AKT-mTOR signaling pathway and promotes the proliferation and invasion of PCa cells through autophagy.

Objective:This study aimed to investigate the safety and efficacy of cadonilimab plus chemotherapy with or without bevacizu-mab in the treatment of recurrent or metastatic cervical cancer(R/M CC).Methods:A retrospective analysis was conducted on 25 patients with R/M CC who were admitted to Tianjin Medical University Cancer Institute&Hospital between August 2022 and June 2024.All patients received cadonilimab plus chemotherapy with or without bevacizumab,followed by cadonilimab as maintenance therapy.Treatment effic-acy and adverse events were comprehensively evaluated,and patients were followed up until October 2024.Results:The median follow-up duration was 18 months(range:4-26 months).The median progression-free survival(PFS)and overall survival were not reached,and the 1-year PFS rate was 77.9%.The objective response rate was 68%,while the disease control rate was 80%.Common adverse reactions in-cluded decreased white blood cell count(40%),nausea(32%),rash(24%),and anemia(24%).No treatment-related deaths occurred during the study period.Conclusions:Cadonilimab plus chemotherapy with or without bevacizumab demonstrated a high objective response rate and a favorable safety profile in patients with R/M CC.However,further studies with larger sample sizes and extended follow-up periods are needed to further validate these findings.

Objective:This study aimed to investigate the safety and efficacy of cadonilimab plus chemotherapy with or without bevacizu-mab in the treatment of recurrent or metastatic cervical cancer(R/M CC).Methods:A retrospective analysis was conducted on 25 patients with R/M CC who were admitted to Tianjin Medical University Cancer Institute&Hospital between August 2022 and June 2024.All patients received cadonilimab plus chemotherapy with or without bevacizumab,followed by cadonilimab as maintenance therapy.Treatment effic-acy and adverse events were comprehensively evaluated,and patients were followed up until October 2024.Results:The median follow-up duration was 18 months(range:4-26 months).The median progression-free survival(PFS)and overall survival were not reached,and the 1-year PFS rate was 77.9%.The objective response rate was 68%,while the disease control rate was 80%.Common adverse reactions in-cluded decreased white blood cell count(40%),nausea(32%),rash(24%),and anemia(24%).No treatment-related deaths occurred during the study period.Conclusions:Cadonilimab plus chemotherapy with or without bevacizumab demonstrated a high objective response rate and a favorable safety profile in patients with R/M CC.However,further studies with larger sample sizes and extended follow-up periods are needed to further validate these findings.

AIM:To investigate the effect of circular RNA MYO9A-006(circMYO9A_006)on hypertrophic phenotype of cardiomyocytes and the underlying mechanism.METHODS:The effect of adenovirus-mediated overexpres-sion of circMYO9A_006 on the expression of hypertrophy-related proteins,including β-myosin heavy chain(β-MHC),skeletal muscle actin alpha 1(ACTA1)and atrial natriuretic peptide(ANP),was evaluated in neonatal mouse ventricular cardiomyocytes(NMVCs).Moreover,a neonatal rat ventricular cardiomyocyte(NRVC)model of phenylephrine(PE)-in-duced hypertrophy was established.The effect of circMYO9A_006 overexpression on NRVC size was ascertained using Phalloidin-iFluor 647 staining method.Dual-luciferase reporter assay was employed to measure the activity of potential in-ternal ribosome entry sites(IRES)in circMYO9A_006.The translation and intracellular location of the circMYO9A_006-translated protein,MYO9A-208aa,were verified using Western blot.To investigate the role of MYO9A-208aa in the ef-fect of circMYO9A_006 on the cardiomyocyte hypertrophic phenotype,we prepared and used the following adenoviruses:the recombinant circMYO9A_006-ORF adenovirus to express MYO9A-208aa,the recombinant circMYO9A_006-ATG-mut adenovirus that does not express MYO9A-208aa,the recombinant circMYO9A_006 adenovirus,and the adenovirus vector control.These were then employed to infect NRVCs.RESULTS:Successful adenovirus-mediated overexpression of circMYO9A_006 was observed in NMVCs.The increased expression of circMYO9A_006 notably reduced the expres-sion of hypertrophy-related proteins in NMVCs(P<0.01).Concurrently,overexpression of circMYO9A_006 substantially reduced the expression of hypertrophy-associated proteins and diminished the size of PE-induced NRVCs(P<0.05).Dual-luciferase reporter assay identified the activity of 2 IRES in circMYO9A_006.Western blot results indicated that circ-MYO9A_006 could produce the MYO9A-208aa protein with an anticipated molecular weight of 28 kD in NRVCs,primari-ly found in the cytoplasm.Elevated expression of both circMYO9A_006 and MYO9A-208aa consistently reduced the ex-pression of hypertrophy-associated proteins(P<0.01),and counteracted the enlarged size of PE-induced NRVCs(P<0.05).However,increased expression of circMYO9A_006-ATG-mut did not counteract the PE-induced hypertrophic phe-notype of NRVCs.CONCLUSION:circMYO9A_006 attenuates the hypertrophic phenotype of cardiomyocytes by synthe-sizing the MYO9A-208aa protein.

ObjectiveTo investigate the effect of circSLC8A1_005 on the fibrotic phenotype of cardiac fibroblasts and the potential mechanism involved. MethodsThe effect of adenovirus-mediated overexpression of circSLC8A1_005 on the expression of fibrosis-related genes， collagen type I alpha 1 chain （Col1a1）， collagen type Ⅲ alpha 1 chain （Col3a1） and smooth muscle actin alpha 2 （Acta2）， in mouse cardiac fibroblasts （mCFs） were detected. The proliferation and migration activities of mCFs were detected by EdU and wound-healing assay， respectively. Dual luciferase reporter gene assay was performed to detect the activity of potential internal ribozyme entry site （IRES） in circSLC8A1_005. CircSLC8A1_005-translated protein， SLC8A1-605aa， and its intracellular distribution was identified by Western blot assay. The effect of SLC8A1-605aa protein on transcription activity of Sod2 gene was detected by the dual luciferase reporter gene assay. RNA binding protein immunoprecipitation （RIP） was utilized to verify the interaction between SLC8A1-605aa and superoxide dismutase 2 （Sod2） mRNA. Actinomycin D treatment was used to detect the effect of SLC8A1-605aa on Sod2 mRNA stability in mCFs. ResultsAn efficient adenovirus-mediated overexpression of circSLC8A1_005 was achieved in mCFs. The enforced expression of circSLC8A1_005 suppressed proliferation and migration of mCFs， and inhibited the expression of fibrosis-related genes in mCFs. The dual luciferase reporter gene assay revealed the activities of 2 IRES in circSLC8A1_005. Results of Western blot assay showed that circSLC8A1_005 could translate protein SLC8A1-605aa with the prospected molecular weight of 70 ku， which is predominantly distributed in the nucleus. Overexpression of the circSLC8A1_005 and SLC8A1-605aa could consistently inhibit the fibrotic phenotype of mCFs. SLC8A1-605aa could up-regulate superoxide dismutase 2 （Sod2） expression， but not at the transcriptional level. RIP assay indicated that SLC8A1-605aa could specifically interact with Sod2 mRNA， and the results of actinomycin D assay showed that SLC8A1-605aa could enhance the stability of Sod2 mRNA in mCFs. ConclusionCircSLC8A1_005 inhibits the fibrotic phenotype of cardiac fibroblasts via translating SLC8A1-605aa protein， and SLC8A1-605aa may be a potential target for the treatment of myocardial fibrosis.

Objective This study aimed to explore the effect of the combined Danzhi Jiangtang Capsule with dapagliflozin on the blood lipid profile and related inflammatory markers in patients with type 2 diabetes mellitus with peripheral vascular disease. Methods 72 patients with type 2 diabetes mellitus with peripheral vascular disease who met the inclusion criteria were admitted to the Department of Endocrinology,The First Affiliated Hospital of Anhui University of Chinese Medicine,from April 2021 to April 2023. The patients were assigned to the experimental group and the control group using the random number table method (36 cases in each group). The control group was treated with dapagliflozin in addition to standard treatment,while the experimental group received the Danzhi Jiangtang Capsule for 12 weeks. Clinical efficacy,glucose and lipid metabolism indicators,hypersensitive C-reactive protein (hs-CRP),body mass index (BMI) levels,and traditional Chinese medicine (TCM) syndrome scores were observed pre-and post-treatment.Results In post-treatment,the clinical efficacy was higher in the experimental group than in the control group. Significant reductions in fasting blood glucose (FPG),2 h postprandial glucose (2 hPG),triglycerides (TG),total cholesterol (TC),low-density lipoprotein cholesterol (LDL-C),hs-CRP,BMI,and increased high-density lipoprotein cholesterol (HDL-C) were observed. Scores for TCM syndrome and individual items also decreased (P<0.05). Comparisons within the groups for pre-and post-treatment showed reductions in FPG,2 hPG,TG,TC,LDL-C,hs-CRP,and an increase in HDL-C,along with a decrease in total scores of TCM syndrome (P<0.05). Conclusion The Danzhi Jiangtang Capsule combined with dapagliflozin in the treatment of type 2 diabetes mellitus with peripheral vascular disease can regulate the blood lipid profile,reduce inflammatory factors,and improve patient's symptoms. Integrated traditional Chinese and Western medicine treatment are more conducive to controlling the disease,and TCM can be used in clinical practice as a combination treatment.

Objective:To study the life characteristics and related risk factors of patients with depression in Shandong Province.Methods:Based on the 2015 mental epidemiological survey database in Shandong Province,a total of 832 patients with depression,807 high-risk individuals with depression,and 819 low-risk individuals were diagnosed according to the Diagnostic and Statistical Manual of Mental Disorders,Fourth Edition(DSM-Ⅳ)and the Structured Clinical Interview for DSM-Ⅳ-TR Axis I Disorders,Research Version(SCID-I/P).In 2020,SCID-I/P was used for re diagnosis,and the General Health Questionnaire(GHQ-12),Simple Quality of Life question-naire,Pittsburgh sleep quality index(PSQI),Childhood Trauma Questionnaire(CTQ),Social Support Rating Scale(SSRS),Global Pain Scale(GPS),Montreal Cognitive Assessment(MoCA),Simplified Coping Style Question-naire(SCSQ)were used for evaluation.Compare changes in the quality of life of depression patients and construct a risk factor model.Results:Patients with depression had lower scores on the simple quality of life questionnaire at baseline and at retest after 5 years than those in the high-and low-risk groups,those in remission of depression had higher scores on the simple quality of life questionnaire at baseline and at retest after 5 years than those in non-re-mission,and those with new-onset disorder in the high-and low-risk groups had lower scores on the simple quality of life questionnaire at baseline and at retest after 5 years than those with no-onset disorder(Ps＜0.001).Depres-sion diagnosis and PSQI scale scores at baseline negatively predicted at retest after 5 years(β=-0.06,-0.15),while coping style tendencies at baseline positively predicted(β=0.06).The simple quality of life questionnaire at baseline negatively predicted depression diagnosis at retest after 5 years,GHQ-12 scores at retest after 5 years,and PSQI scale scores at retest after 5 years(β=-0.11,-0.17,-0.09),while the simple quality of life question-naire at baseline positively predicted coping style tendencies at retest after 5 years(β=0.13).Depression diagnosis at retest after 5 years,GHQ-12 scores at retest after 5 years,PSQI scale scores at retest after 5 years,coping style tendencies at retest after 5 years,SSRS scale scores,CTQ scale scores,GPS scale scores,and the simple quality of life questionnaire at baseline all influenced the simple quality of life questionnaire at retest after 5 years through ei-ther direct or indirect pathways.Conclusion:It suggest that the quality of life is lower in patients with depression than in the general population.Depression diagnosis,sleep,mental health,pain,social support,childhood trauma and coping are direct and indirect risk factors affecting life.

Objective:To evaluate changes in operational effectiveness after the implementation of ambulatory surgical management in pars plana vitrectomy (PPV).Methods:A retrospective clinical study. 17 528 surgeries in 10 895 eyes of 10 895 patients who underwent minimally invasive PPV on an ambulatory and/or inpatient basis at Tianjin Medical University Eye Hospital from August 2015 to June 2023 were included in this study. Among them, 5 346 eyes in 5 346 cases were male; 5 549 eyes in 5 549 cases were female. The age ranged from 0 to 95 years, with the mean age of (57.74±13.15) years. 6 381 surgeries in 3 615 eyes from August 2015 to December 2018 (the initial period of day surgery) were used as the control group; 11 147 surgeries in 7 280 eyes from January 2019 to June 2023 (the expanded period of day surgery) were used as the observation group. According to the management mode of ambulatory surgery, the observation group was subdivided into the decentralized management group (January 2019 to December 2020) and the centralized management group (January 2021 to June 2023), with 2 905 and 4 375 eyes and 4 646 and 6 501 surgeries, respectively. Changes in the percentage of day surgery, average hospitalization days, and average unplanned reoperation rate were compared. The Mann-Whitney U test was used to compare numerical variables between groups; the chi-square test or Fisher's exact test was used to compare categorical variables. Results:The number of cases of daytime PPV performed in the observation group and control group was 7 852 (70.44%, 7 852/11 147) and 24 (0.38%, 24/6 381) cases, respectively, and the average hospitalization days were 1 (1) and 5 (3) d. Compared with the control group, the observation group had a significantly higher percentage of day surgery ( χ2=8 051.01) and a considerably lower mean hospitalization day ( Z=4 536 844.50), and the differences were statistically significant ( P<0.000 1). The mean hospitalization days in the decentralized and centralized management groups were 2 (3) and 1 (0) d, respectively, and unplanned reoperations were 34 (0.73%, 34/4 646) and 171 (2.63%, 171/6 501) eyes, respectively. Compared with the decentralized management group, average hospitalization days was significantly lower ( Z=1 436.94) and unplanned reoperation rate was significantly higher ( χ2=54.10) were significantly lower in the centralized management group, both of which were statistically significant ( P<0.000 1). Conclusion:PPV ambulatory management model can significantly reduce the average hospitalization day, but also results in higher rates of unplanned reoperations.

Visual hallucination(VH)is a common symptom of schizophrenia,the underlying mechanism has not been fully elucidated.It has been found that the dysfunction of dopamine(DA)system,the overactivation of α-amino-3-hydroxy-5-methyl-4-isoxazole-propionate(AMPA)receptor in glutamate system and the dysfunction of γ-aminobutyric acid(GABA)ergic neurons can induce VH in patients with schizophrenia.In addition,abnormalities in brain structural and functional networks and visual networks are also closely related to the occurrence of VH.The purpose of this paper is to review the neurochemistry and nerve injury mechanism of VH in schizophrenic patients to deeply understand the characteristics of VH,and make more accurate judgment in the early diagnosis,condition evaluation and treatment plan of schizophrenic patients.

Objective:To evaluate the effect of intraoperative individualized systolic blood pressure (SBP) management on myocardial injury after hip replacement in elderly patients at high risks of hypertension.Methods:One hundred and eighty-two patients of either sex, aged 60-89 yr, with body mass index of 18-26 kg/m 2, with a history of hypertension requiring drug treatment and stratified high risk factors of cardiovascular risk factors, scheduled for elective hip replacement under general anesthesia, were divided into 2 groups ( n=91 each) using a random number table method: routine management group and individualized SBP management group. Individualized SBP management group maintained the intraoperative SBP at 90%-110% of the baseline value, and routine management group implemented blood pressure management according to the current routine clinical pathway.The intermedian cubital venous blood samples were collected before surgery and at 24, 48, and 72 h after surgery for determination of the serum concentrations of high sensitivity cardiac troponin T. Postoperative myocardial injury and myocardial infarction were also recorded. The 30-day all-cause mortality was recorded on day 30 after surgery. Results:The incidence of postoperative myocardial injury and serum concentrations of high sensitivity cardiac troponin T at 24, 48 and 72 h after surgery were significantly decreased, and the length of hospital stay was shortened in individualized SBP management group as compared with routine management group ( P<0.05). Conclusions:Intraoperative individualized SBP management can reduce the postoperative myocardial injury in elderly patients at high risk of hypertension undergoing hip replacement.