This study was aimed at investigating the effects of demethylase fat mass and obesity-associated protein(FTO)and methyltransferase methyltransferase like protein 3(METTL3),key molecules in N6-methyladenosine(m6A)modification,on the replication and proliferation of Japanese encephalitis virus(JEV).Recombinant lentiviruses were generated by packaging the FTO and green fluorescent protein into lentiviral vectors.Neuro2a cells,a mouse neuroblastoma cell line,were infected with the lentivirus,and stable FTO-expressing cell lines were obtained through puromycin selection.Successful overexpression of FTO was confirmed through fluorescence microscopy,real-time quantitative PCR,and western blot analysis.When Neuro2a cells overexpressing FTO were infected with JEV,the overexpression of FTO decreased JEV replication in the cells,and increased the expression of interferon(IFN)and related molecules.Additionally,treatment of JEV-infected Neuro2a cells with the METTL3-specific inhibitor STM2457 resulted in a dose-dependent decrease in JEV replication and viral protein expression.These findings suggested that lowering m6A methylation levels inhibits JEV replication,thus shedding light on the regulatory role of methylation modification in JEV replication.

This paper aims to study the effect of Ziziphi Spinosae Semen extracts on chronic unpredictable mild stress(CUMS)-induced depression-like and insomnia behavior models of mice. The CUMS-induced depression-like and insomnia behavior model of mice was established by CUMS treatment for three weeks. The mice were randomly divided into control group, model group, positive drug diazepam group(2 mg·kg~(-1)), as well as low-dose group(1.95 g·kg~(-1)), medium-dose group(3.9 g·kg~(-1)), and high-dose group(7.8 g·kg~(-1)) of Ziziphi Spinosae Semen extracts, with 18 mice in each group. On the 15th day of modeling, the drug was administered intragastrically once a day for one week. Then, the pentobarbital sodium cooperative righting experiment, open field experiment, and elevated plus maze experiment were carried out, respectively. The contents of neurotransmitters 5-hydroxytryptamine(5-HT) and 5-hydroxyindoleacetic acid(5-HIAA) in serum and thalamus of mice, as well as the levels of corticotropin releasing hormone(CRH), adrenocorticotropic hormone(ACTH), and corticosterone(CORT) in serum, were determined by enzyme-linked immunosorbent assay(ELISA). The neuron damage in the hippocampus of mice was observed by hematoxylin-eosin(HE) staining and Nissl staining. Western blot was used to detect the expressions of tryptophan hydroxylase 2(TPH2), serotonin transporter(SERT), monoamine oxidase A(MAOA), five prime repressors under dual repression binding protein 1(Freud1), synaptic plasticity-related proteins [cellular gene FOS(C-FOS), postsynaptic density protein 95(PSD95), synapsin 1(SYN1), and activity-regulated cytoskeleton-associated gene(ARC)], blood-brain barrier(BBB) permeability-related proteins [zonula occludens 1(ZO-1), occludin, and claudin 1], inflammatory factors [NOD-, LRR-and pyrin domain-containing protein 3(NLRP3), apoptosis-associated speck-like protein(ASC), gasdermin D(GSDMD), caspase-3, and caspase-8], and antioxidant factors [nuclear factor erythroid 2-related factor 2(NRF2) and heme oxygenase 1(HO1)] in thalamic tissue of mice. The results indicated that compared with that in the model group, the sleep latency was significantly shortened, and the sleep duration was significantly prolonged in each dose group of Ziziphi Spinosae Semen extracts. The number of visits to the central area of the open field and the distance and time of visits were significantly increased in each dose group of Ziziphi Spinosae Semen extracts. In addition, the proportion of distance and time of entering the open arm area of the elevated plus maze was significantly increased in each dose group of Ziziphi Spinosae Semen extracts. The contents of 5-HT and 5-HIAA in serum and thalamus of mice increased to varying degrees in each dose group of Ziziphi Spinosae Semen extracts; the contents of CRH, ACTH, and CORT in serum of mice were significantly decreased. The protein expression of TPH2 was significantly increased. The protein expression of MAOA, SERT, and Freud1 was significantly decreased. Ziziphi Spinosae Semen extracts could also significantly reduce the protein expression of C-FOS but significantly increase the protein expression of PSD95, ARC, and SYN1. They could reduce the pathological damage of the hippocampus in mice and significantly increase the protein expression of ZO-1, occluding, and claudin 1. The protein expression of NLRP3, GSDMD, ASC, caspase-3, and caspase-8 in the thalamic tissue of mice was significantly decreased, and the protein expression of HO1 and NRF2 was significantly increased. In conclusion, Ziziphi Spinosae Semen extracts could effectively improve sleep disorders and depression-like behaviors in CUMS-induced model mice, which may be related to regulating the 5-HT anabolism process and hypothalamic-pituitary-adrenal(HPA) axis-related hormone levels, reducing pathological damage in the hippocampus, improving synaptic plasticity, repairing BBB integrity, and alleviating inflammatory response and oxidative stress damage.
Animals ; Ziziphus/chemistry* ; Mice ; Male ; Depression/psychology* ; Drugs, Chinese Herbal/administration & dosage* ; Sleep Initiation and Maintenance Disorders/psychology* ; Stress, Psychological/complications* ; Behavior, Animal/drug effects* ; Humans ; Disease Models, Animal

Objective:To investigate the factors influencing early recurrence for patients with initially unresectable hepatocellular carcinoma (HCC) who underwent salvage liver resection (SLR) following transcatheter arterial chemoembolization-based downstaging treatment, and construct a predictive model to evaluate its predicting performance.Methods:The retrospective cohort study was constructed. The clinicopathological data of 305 patients with initially unresectable HCC who were admitted to 4 medical centers in China, including the Third Affiliated Hospital of Naval Medical University (Shanghai Eastern Hepatobiliary Surgery Hospital) et al, from January 2019 to December 2021 were collected. There were 286 males and 19 females, aged (48.7±10.4)years. A total of 133 patients who were admitted from January 2019 to December 2020 were set as the training cohort, and the other 172 patients who were admitted from January to December 2021 were set as the validation cohort. Observation indicators: (1) postoperative recurrence-free survival in HCC patients; (2) analysis of factors influencing postoperative early recurrence in HCC patients; (3) construction and validation of the predictive model. Comparison of measurement data with normal distribution between groups was conducted using the independent sample t test. Comparison of count data between groups was conducted using the chi-square test. Comparison of ordinal data was conducted using the rank sum test. Univariate and multivariate analyses were conducted using the Cox regre-ssion model. The Kaplan-Meier method was used to calculate survival. The Log-rank test was used for survival analysis. The predicting performance of the model was evaluated using the concordance index (C-index) and the area under curve (AUC) of time-dependent receiver operating characteristic (ROC) curve, and the accuracy of the model was validated using the calibration curve. The total net gain of the model was evaluated using the decision curve. Results:(1) Postoperative recurrence-free survival in HCC patients. The recurrence-free survival time of 133 HCC patients in the training cohort was 10.0(range, 1.5-24.0)months, with 1-, 2-year recurrence-free survival rate of 47.3% and 36.8%. The recurrence-free survival time of 172 HCC patients in the validation cohort was 11.0(range, 1.0-24.0)months, with 1-, 2-year recurrence-free survival rate of 51.7% and 37.2%. There was no significant difference in recurrence-free survival between patients in the training cohort and the validation cohort ( χ2=0.075, P>0.05). (2) Analysis of factors influencing postoperative early recur-rence in HCC patients. Results of multivariate analysis showed that tumor burden prior to down-staging treatment, grade of albumin-bilirubin (ALBI) score prior to SLR, alpha-fetoprotein (AFP) half-life prior to SLR, and tumor response prior to SLR were independent factors influencing early recurrence in HCC patients after surgery [ hazard ratio=3.212, 2.526, 2.304, 1.575, 95% confidence interal ( CI) as 1.262-8.175, 1.324-4.818, 1.477-3.595, 1.138-2.180, P<0.05]. (3) Construction and validation of the predictive model. A nomogram predictive model for postoperative early recurrence was constructed base on the results of multivariate analysis. The C-index of predictive model was 0.786 for the training cohort and 0.734 for the validation cohort. The AUC of ROC curve of nomogram predictive model for 12-, 18-, and 24-month recurrence-free survival rate in the training cohort were 0.890 (95% CI as 0.836-0.944), 0.895 (95% CI as 0.842-0.947), and 0.887 (95% CI as 0.831-0.942), respectively. The AUC of ROC curve of nomogram predictive model for 12-, 18-, and 24-month recurrence-free survival rate in the validation cohort were 0.845 (95% CI as 0.781-0.909], 0.888 (95% CI as 0.826-0.950), and 0.919 (95% CI as 0.870-0.968), respectively. Results of calibration curve showed high consistency between the predicted results of nomogram predictive model and actual outcomes. Results of decision curve showed the nomogram predictive model with a good total net gain at a threshold of 0.10-0.50. Conclusions:Tumor burden prior to downstaging treatment, grade of ALBI score prior to SLR, AFP half-life prior to SLR, and tumor response prior to SLR are independent factors influencing early recurrence in initially unresectable HCC patients undergoing SLR following downstaging treatment. The nomogram predictive model based on these factors can effectively evaluate the prognosis of this patient population.

The overall revision of ISO 10555-1:2023 Intravascular catheters—Sterile and single-use catheters—Part 1:General requirements was introduced,which was compared with YY 0285.1-2017 Intravascular catheters—Sterile and sing-use catheters—Part 1:General requirements in terms of terminology definition,requirements and identification of nominal size.The new and changed contents of ISO 10555-1:2023 were interpreted,and references were provided for the develop-ment,inspection and testing and supervision of related products and for the future revision of YY 0285.1-2017 standard.[Chinese Medical Equipment Journal,2025,46(10):65-70]

The overall revision of ISO 10555-1:2023 Intravascular catheters—Sterile and single-use catheters—Part 1:General requirements was introduced,which was compared with YY 0285.1-2017 Intravascular catheters—Sterile and sing-use catheters—Part 1:General requirements in terms of terminology definition,requirements and identification of nominal size.The new and changed contents of ISO 10555-1:2023 were interpreted,and references were provided for the develop-ment,inspection and testing and supervision of related products and for the future revision of YY 0285.1-2017 standard.[Chinese Medical Equipment Journal,2025,46(10):65-70]

This study was aimed at investigating the effects of demethylase fat mass and obesity-associated protein(FTO)and methyltransferase methyltransferase like protein 3(METTL3),key molecules in N6-methyladenosine(m6A)modification,on the replication and proliferation of Japanese encephalitis virus(JEV).Recombinant lentiviruses were generated by packaging the FTO and green fluorescent protein into lentiviral vectors.Neuro2a cells,a mouse neuroblastoma cell line,were infected with the lentivirus,and stable FTO-expressing cell lines were obtained through puromycin selection.Successful overexpression of FTO was confirmed through fluorescence microscopy,real-time quantitative PCR,and western blot analysis.When Neuro2a cells overexpressing FTO were infected with JEV,the overexpression of FTO decreased JEV replication in the cells,and increased the expression of interferon(IFN)and related molecules.Additionally,treatment of JEV-infected Neuro2a cells with the METTL3-specific inhibitor STM2457 resulted in a dose-dependent decrease in JEV replication and viral protein expression.These findings suggested that lowering m6A methylation levels inhibits JEV replication,thus shedding light on the regulatory role of methylation modification in JEV replication.

Objective:To investigate the factors influencing early recurrence for patients with initially unresectable hepatocellular carcinoma (HCC) who underwent salvage liver resection (SLR) following transcatheter arterial chemoembolization-based downstaging treatment, and construct a predictive model to evaluate its predicting performance.Methods:The retrospective cohort study was constructed. The clinicopathological data of 305 patients with initially unresectable HCC who were admitted to 4 medical centers in China, including the Third Affiliated Hospital of Naval Medical University (Shanghai Eastern Hepatobiliary Surgery Hospital) et al, from January 2019 to December 2021 were collected. There were 286 males and 19 females, aged (48.7±10.4)years. A total of 133 patients who were admitted from January 2019 to December 2020 were set as the training cohort, and the other 172 patients who were admitted from January to December 2021 were set as the validation cohort. Observation indicators: (1) postoperative recurrence-free survival in HCC patients; (2) analysis of factors influencing postoperative early recurrence in HCC patients; (3) construction and validation of the predictive model. Comparison of measurement data with normal distribution between groups was conducted using the independent sample t test. Comparison of count data between groups was conducted using the chi-square test. Comparison of ordinal data was conducted using the rank sum test. Univariate and multivariate analyses were conducted using the Cox regre-ssion model. The Kaplan-Meier method was used to calculate survival. The Log-rank test was used for survival analysis. The predicting performance of the model was evaluated using the concordance index (C-index) and the area under curve (AUC) of time-dependent receiver operating characteristic (ROC) curve, and the accuracy of the model was validated using the calibration curve. The total net gain of the model was evaluated using the decision curve. Results:(1) Postoperative recurrence-free survival in HCC patients. The recurrence-free survival time of 133 HCC patients in the training cohort was 10.0(range, 1.5-24.0)months, with 1-, 2-year recurrence-free survival rate of 47.3% and 36.8%. The recurrence-free survival time of 172 HCC patients in the validation cohort was 11.0(range, 1.0-24.0)months, with 1-, 2-year recurrence-free survival rate of 51.7% and 37.2%. There was no significant difference in recurrence-free survival between patients in the training cohort and the validation cohort ( χ2=0.075, P>0.05). (2) Analysis of factors influencing postoperative early recur-rence in HCC patients. Results of multivariate analysis showed that tumor burden prior to down-staging treatment, grade of albumin-bilirubin (ALBI) score prior to SLR, alpha-fetoprotein (AFP) half-life prior to SLR, and tumor response prior to SLR were independent factors influencing early recurrence in HCC patients after surgery [ hazard ratio=3.212, 2.526, 2.304, 1.575, 95% confidence interal ( CI) as 1.262-8.175, 1.324-4.818, 1.477-3.595, 1.138-2.180, P<0.05]. (3) Construction and validation of the predictive model. A nomogram predictive model for postoperative early recurrence was constructed base on the results of multivariate analysis. The C-index of predictive model was 0.786 for the training cohort and 0.734 for the validation cohort. The AUC of ROC curve of nomogram predictive model for 12-, 18-, and 24-month recurrence-free survival rate in the training cohort were 0.890 (95% CI as 0.836-0.944), 0.895 (95% CI as 0.842-0.947), and 0.887 (95% CI as 0.831-0.942), respectively. The AUC of ROC curve of nomogram predictive model for 12-, 18-, and 24-month recurrence-free survival rate in the validation cohort were 0.845 (95% CI as 0.781-0.909], 0.888 (95% CI as 0.826-0.950), and 0.919 (95% CI as 0.870-0.968), respectively. Results of calibration curve showed high consistency between the predicted results of nomogram predictive model and actual outcomes. Results of decision curve showed the nomogram predictive model with a good total net gain at a threshold of 0.10-0.50. Conclusions:Tumor burden prior to downstaging treatment, grade of ALBI score prior to SLR, AFP half-life prior to SLR, and tumor response prior to SLR are independent factors influencing early recurrence in initially unresectable HCC patients undergoing SLR following downstaging treatment. The nomogram predictive model based on these factors can effectively evaluate the prognosis of this patient population.

Purpose::Although traditional craniotomy (TC) surgery has failed to show benefits for the functional outcome of intracerebral hemorrhage (ICH). However, a minimally invasive hematoma removal plan to avoid white matter fiber damage may be a safer and more feasible surgical approach, which may improve the prognosis of ICH. We conducted a historical cohort study on the use of multimodal image fusion-assisted neuroendoscopic surgery (MINS) for the treatment of ICH, and compared its safety and effectiveness with traditional methods.Methods::This is a historical cohort study involving 241 patients with cerebral hemorrhage. Divided into MINS group and TC group based on surgical methods. Multimodal images (CT skull, CT angiography, and white matter fiber of MRI diffusion-tensor imaging) were fused into 3 dimensional images for preoperative planning and intraoperative guidance of endoscopic hematoma removal in the MINS group. Clinical features, operative efficiency, perioperative complications, and prognoses between 2 groups were compared. Normally distributed data were analyzed using t-test of 2 independent samples, Nonnormally distributed data were compared using the Kruskal-Wallis test. Meanwhile categorical data were analyzed via the Chi-square test or Fisher’s exact test. All statistical tests were two-sided, and p < 0.05 was considered statistically significant. Results::A total of 42 patients with ICH were enrolled, who underwent TC surgery or MINS. Patients who underwent MINS had shorter operative time ( p < 0.001), less blood loss ( p < 0.001), better hematoma evacuation ( p =0.003), and a shorter stay in the intensive care unit ( p =0.002) than patients who underwent TC. Based on clinical characteristics and analysis of perioperative complications, there is no significant difference between the 2 surgical methods. Modified Rankin scale scores at 180 days were better in the MINS than in the TC group ( p =0.014). Conclusions::Compared with TC for the treatment of ICH, MINS is safer and more efficient in cleaning ICH, which improved the prognosis of the patients. In the future, a larger sample size clinical trial will be needed to evaluate its efficacy.

YY 0585.4-2009 and ISO 8536-12:2021 standards were compared in terms of the blocking performance test method of disposable check valves for infusion equipment.The affecting factors and possible errors were analyzed when the blocking performance test was carried out according to YY 0585.4-2009,and it's pointed out ISO 8536-12:2021 gained advantages over YY 0585.4-2009 in the blocking performance test method of check valves.References and guidance were provided for standard revision and actual operation.[Chinese Medical Equipment Journal,2024,45(9):78-83]

Background: Bulky or multiple lymph node (LN) metastases are associated with poor prognosis in cervical cancer, and the size or number of LN metastases is not yet reflected in the staging system and therapeutic strategy. Although the therapeutic effects of surgical resection of bulky LNs before standard treatment have been reported in several retrospective studies, wellplanned randomized clinical studies are lacking. Therefore, the aim of the Korean Gynecologic Oncology Group (KGOG) 1047/DEBULK trial is to investigate whether the debulking surgery of bulky or multiple LNs prior to concurrent chemoradiation therapy (CCRT) improves the survival rate of patients with cervical cancer IIICr diagnosed by imaging tests. Methods The KGOG 1047/DEBULK trial is a phase III, multicenter, randomized clinical trial involving patients with bulky or multiple LN metastases in cervical cancer IIICr. This study will include patients with a short-axis diameter of a pelvic or para-aortic LN ≥2 cm or ≥3 LNs with a short-axis diameter ≥1 cm and for whom CCRT is planned. The treatment arms will be randomly allocated in a 1:1 ratio to either receive CCRT (control arm) or undergo surgical debulking of bulky or multiple LNs before CCRT (experimental arm). CCRT consists of extended-field external beam radiotherapy/pelvic radiotherapy, brachytherapy and LN boost, and weekly chemotherapy with cisplatin (40 mg/m 2 ), 4–6 times administered intravenously.The primary endpoint will be 3-year progression-free survival rate. The secondary endpoints will be 3-year overall survival rate, treatment-related complications, and accuracy of radiological diagnosis of bulky or multiple LNs.