Background: and Purpose Vertebrobasilar fusiform aneurysms (VBFAs) carry substantial morbidity and mortality, but optimal management for unruptured VBFAs remains unclear. We compared the safety and efficacy of conservative management (CM), stent-assisted coiling (SAC), and flow diverters (FDs) in patients with unruptured VBFAs, focusing on long-term prognosis. Methods: This study included data from a nationwide Chinese cohort of patients with vertebrobasilar dissecting aneurysms. Inverse probability of treatment weighting (IPTW) balanced confounders across groups. The primary outcome was poor prognosis (modified Rankin Scale score >2). Secondary outcomes included aneurysm rupture, ischemic stroke, compression symptoms, and VBFA-related deaths. Logistic regression estimated odds ratios (ORs) and 95% confidence intervals (CIs). Subgroup and sensitivity analyses were performed. Results: Among 1,115 patients with unruptured VBFAs, 838 (median age, 54 years; 655 men) were included. After IPTW, baseline characteristics were balanced. Median follow-up was 54 months. FD was associated with a lower risk of poor prognosis than CM (OR, 0.48 [95% CI, 0.30 to 0.77]; p=0.002), with no difference between CM and SAC. FD also reduced aneurysm rupture (OR, 0.20 [95% CI, 0.07 to 0.60]; p=0.004) and compression symptoms (OR, 0.30 [95% CI, 0.13 to 0.68]; p=0.004) versus CM. Time-to-event analyses further revealed significant differences in vertebral artery lesions and Type I–II VBFAs, whereas no significant differences were observed in basilar or vertebrobasilar junction lesions or in Type III–IV VBFAs. Conclusions Compared with CM, FD was associated with improved long-term outcomes in unruptured VBFAs, particularly in vertebral artery lesions and Type I–II VBFAs, although residual confounding cannot be excluded.

Objective:To assess the impact of elderly medical and nursing services pilots on the health of the elderly and its differentiated effects.Methods:Using five-period unbalanced panel data from China Longitudinal Aging Social Survey conducted between 2014 and 2023,the study employed a PSM-DID method to analyze changes in the health status of the elderly before and after the reform.Results:The pilots significantly improved the health status of the elderly,with the policy's effects most notably enhancing their psychological health.The elderly groups at a disadvantage in terms of resources,such as those with advanced age,low educational levels,or living apart from their children,can obtain greater mental health benefits from the pilots.The long-term care insurance and elderly medical care services pilots formed a policy synergy,but the implementation of multiple overlapping policies may attenuate the pilot's effects.Conclusions:The pilots have yielded initial results,but there is still considerable room for improvement.It is recommended to actively promote the integration of regional medical and nursing resources,precisely meet the needs of disadvantaged the elderly groups,and strengthen interdepartmental collaboration and information sharing.

Objective:To assess the impact of elderly medical and nursing services pilots on the health of the elderly and its differentiated effects.Methods:Using five-period unbalanced panel data from China Longitudinal Aging Social Survey conducted between 2014 and 2023,the study employed a PSM-DID method to analyze changes in the health status of the elderly before and after the reform.Results:The pilots significantly improved the health status of the elderly,with the policy's effects most notably enhancing their psychological health.The elderly groups at a disadvantage in terms of resources,such as those with advanced age,low educational levels,or living apart from their children,can obtain greater mental health benefits from the pilots.The long-term care insurance and elderly medical care services pilots formed a policy synergy,but the implementation of multiple overlapping policies may attenuate the pilot's effects.Conclusions:The pilots have yielded initial results,but there is still considerable room for improvement.It is recommended to actively promote the integration of regional medical and nursing resources,precisely meet the needs of disadvantaged the elderly groups,and strengthen interdepartmental collaboration and information sharing.

Aim To explore the mechanism of action of Guizhi Jia Gegen decoction(GGD)in treating pneu-monia-enteritis induced by H1N1 influenza virus infec-tion in a mouse model,using network pharmacology and molecular docking techniques,followed by in vivo verification.Methods A pneumonia-enteritis mouse model was established,and the intervention effects of GGD on the model mice were evaluated using indica-tors such as body weight,rectal temperature,lung in-dex,colon length,H1N1 M gene expression,relative mRNA expression levels of inflammatory cytokines,and pathological sections of the lung and intestine.The targets of the blood-absorbed components of GGD were identified using the Swiss Target Prediction platform,and the disease targets were retrieved from the Gene-Cards platform.The intersecting targets were analyzed through PPI network analysis using the STRING data-base to identify core targets.GO analysis and KEGG pathway enrichment analysis were performed using the Metascape database.RT-qPCR was employed to vali-date the core targets and pathways.Molecular docking was conducted using AutoDock Tools software to verify the interactions between blood-absorbed components and key targets.Results GGD demonstrated signifi-cant therapeutic effects on the pneumonia-enteritis mouse model.The results of network pharmacology in-dicated that the therapeutic effects of GGD were strong-ly associated with targets such as TNF,ALB,PTGS2,MMP9,EGFR,ESR1,SRC,HSP90AA1,PPARG and MMP2.RT-qPCR results indicated that GGD could intervene in pneumonia-enteritis by regulating the targets TNF,ALB,EGFR and the related targets of the NF-κB pathway.Molecular docking results re-vealed that blood-absorbed components such as puerar-in and liquiritin could stably bind to TNF,ALB and EGFR.Conclusion Components such as puerarin and liquiritin in GGD may exert therapeutic effects on pneumonia-enteritis induced by H1N1 influenza virus infection by acting on targets such as TNF,ALB and EGFR.

Objective To analyze the influencing factors of lymph node metastasis(DLN)metastasis in patients with differentiated thyroid carcinoma(DTC)and construct a column chart.Methods A total of 245 DTC patients who underwent surgical treatment in our hospital from January 2018 to December 2023 were selected.They were separated into two groups based on whether DLN metastasis occurred:the DLN metastasis group(119 cases)and the non DLN metastasis group(126 cases).Logistic regression analysis was applied to screen for risk factors for DLN metastasis in DTC patients.R software was applied to draw a nomogram prediction model for predicting DLN metastasis in DTC patients.Receiver operating characteristic(ROC)curves,calibration curves,and Hosmer-Lemeshow goodness of fit tests were applied to evaluate column charts.Results Logistic regression analysis revealed that gender of"male",multiple lesions,capsule invasion,intranodular calcification,and antithyroglobulin antibodies(TGAb)positivity were independent risk factors for DLN metastasis in DTC patients(P＜0.05).The area under the ROC curve was 0.807(95％CI:0.753-0.861).The slope of the calibration curve was close to 1,and the Hosmer-Lemeshow goodness of fit test showed x2=8.983,P=0.344.Conclusion A column chart constructed based on five independent risk factors,including male,multiple lesions,capsule invasion,intranodular calcification,and TGAb positive,can effectively predict the risk of DLN metastasis in DTC patients.

Objective To analyze the influencing factors of lymph node metastasis(DLN)metastasis in patients with differentiated thyroid carcinoma(DTC)and construct a column chart.Methods A total of 245 DTC patients who underwent surgical treatment in our hospital from January 2018 to December 2023 were selected.They were separated into two groups based on whether DLN metastasis occurred:the DLN metastasis group(119 cases)and the non DLN metastasis group(126 cases).Logistic regression analysis was applied to screen for risk factors for DLN metastasis in DTC patients.R software was applied to draw a nomogram prediction model for predicting DLN metastasis in DTC patients.Receiver operating characteristic(ROC)curves,calibration curves,and Hosmer-Lemeshow goodness of fit tests were applied to evaluate column charts.Results Logistic regression analysis revealed that gender of"male",multiple lesions,capsule invasion,intranodular calcification,and antithyroglobulin antibodies(TGAb)positivity were independent risk factors for DLN metastasis in DTC patients(P＜0.05).The area under the ROC curve was 0.807(95％CI:0.753-0.861).The slope of the calibration curve was close to 1,and the Hosmer-Lemeshow goodness of fit test showed x2=8.983,P=0.344.Conclusion A column chart constructed based on five independent risk factors,including male,multiple lesions,capsule invasion,intranodular calcification,and TGAb positive,can effectively predict the risk of DLN metastasis in DTC patients.

Aim To explore the mechanism of action of Guizhi Jia Gegen decoction(GGD)in treating pneu-monia-enteritis induced by H1N1 influenza virus infec-tion in a mouse model,using network pharmacology and molecular docking techniques,followed by in vivo verification.Methods A pneumonia-enteritis mouse model was established,and the intervention effects of GGD on the model mice were evaluated using indica-tors such as body weight,rectal temperature,lung in-dex,colon length,H1N1 M gene expression,relative mRNA expression levels of inflammatory cytokines,and pathological sections of the lung and intestine.The targets of the blood-absorbed components of GGD were identified using the Swiss Target Prediction platform,and the disease targets were retrieved from the Gene-Cards platform.The intersecting targets were analyzed through PPI network analysis using the STRING data-base to identify core targets.GO analysis and KEGG pathway enrichment analysis were performed using the Metascape database.RT-qPCR was employed to vali-date the core targets and pathways.Molecular docking was conducted using AutoDock Tools software to verify the interactions between blood-absorbed components and key targets.Results GGD demonstrated signifi-cant therapeutic effects on the pneumonia-enteritis mouse model.The results of network pharmacology in-dicated that the therapeutic effects of GGD were strong-ly associated with targets such as TNF,ALB,PTGS2,MMP9,EGFR,ESR1,SRC,HSP90AA1,PPARG and MMP2.RT-qPCR results indicated that GGD could intervene in pneumonia-enteritis by regulating the targets TNF,ALB,EGFR and the related targets of the NF-κB pathway.Molecular docking results re-vealed that blood-absorbed components such as puerar-in and liquiritin could stably bind to TNF,ALB and EGFR.Conclusion Components such as puerarin and liquiritin in GGD may exert therapeutic effects on pneumonia-enteritis induced by H1N1 influenza virus infection by acting on targets such as TNF,ALB and EGFR.

Objective:To investigate the impact of donor age on early postoperative liver function recovery in liver transplant recipients, as well as the incidence and risk factors for arterial complications following liver transplantation.Methods:A total of 518 patients who underwent liver transplantation at the Organ Transplantation Center of the Affiliated Hospital of Qingdao University between January 2021 and January 2024 were included in the study. Based on donor age, patients were classified into the elderly donor group (≥70 years, n=28) and the non-elderly donor group (<70 years, n=490). Liver function indicators—including aspartate aminotransferase (AST), alanine aminotransferase (ALT), total bilirubin (TBIL), and direct bilirubin (DBIL)—were measured on postoperative days 1, 3, 7, and 14. The incidence of arterial complications, including hepatic artery thrombosis and hepatic artery stenosis, was recorded. Recipients were further categorized into the arterial complication group (n=26) and the non-arterial complication group (n=492) based on postoperative outcomes, and clinical characteristics of donors and recipients were compared. Binary logistic regression analysis was conducted to identify risk factors for arterial complications.Rusults:No significant differences were observed in baseline characteristics between the elderly and non-elderly donor groups ( P>0.05). However, the elderly donor group exhibited significantly higher AST, ALT, TBIL, and DBIL levels at all postoperative time points compared to the non-elderly donor group (all P<0.05). Specifically, on postoperative day 1, AST and ALT levels were (1,024.57±256.49) U/L and (756.24±145.89) U/L in the elderly donor group, compared to (895.23±225.19) U/L and (614.85±126.51) U/L in the non-elderly donor group. On day 3, AST and ALT levels were (402.46±71.61) U/L and (423.31±87.44) U/L versus (226.37±66.54) U/L and (256.79±70.25) U/L, respectively. On day 7, AST and ALT levels were (91.78±21.84) U/L and (92.36±21.62) U/L versus (68.41±18.38) U/L and (77.47±18.16) U/L. By day 14, AST and ALT levels were (67.52±10.35) U/L and (72.17±16.28) U/L versus (35.32±9.27) U/L and (48.56±14.10) U/L, respectively ( P<0.05 for all comparisons). For bilirubin indicators, TBIL and DBIL levels in the elderly donor group were also consistently higher than in the non-elderly donor group. On day 1, TBIL and DBIL were (95.76±21.93) μmol/L and (64.22±15.07) μmol/L, compared to (77.59±20.48) μmol/L and (51.18±12.96) μmol/L. By day 14, TBIL and DBIL levels had decreased to (41.26±8.30) μmol/L and (32.45±6.21) μmol/L, compared to (28.39±7.15) μmol/L and (20.58±5.04) μmol/L in the non-elderly donor group ( P<0.05 for all comparisons). The incidence of hepatic artery complications was 10.71% (3/28) in the elderly donor group and 4.69% (23/490) in the non-elderly donor group, with no statistically significant difference between the two groups ( P>0.05). Statistical analysis employing independent t-tests and χ2 tests demonstrated significant differences between the arterial complication group and non-arterial complication group in donor quality ratio ( P<0.05) and incidence of hepatic arterial hypoperfusion ( P<0.05). Multivariate binary logistic regression analysis, after adjusting for confounding factors (e.g., recipient gender, age, body mass index [BMI], primary disease, and donor-recipient blood type compatibility), identified recipient-to-donor mass ratio ( OR=1.352, P<0.05) and insufficient hepatic arterial blood flow ( OR=1.497, P<0.05) as independent risk factors for arterial complications following liver transplantation. Conclusion:Elderly liver donors can have a certain impact on early postoperative liver function recovery in liver transplant recipients, but have no significant impact on the occurrence of arterial complications after liver transplantation. The mass ratio of recipients to donors and insufficient hepatic arterial blood flow are independent risk factors for arterial complications after liver transplantation.

OBJECTIVE: Gastric cancer (GC) is one of the most common malignancies seen in clinic and requires novel treatment options. Morin is a natural flavonoid extracted from the flower stalk of a highly valuable medicinal plant Prunella vulgaris L., which exhibits an anti-cancer effect in multiple types of tumors. However, the therapeutic effect and underlying mechanism of morin in treating GC remains elusive. The study aims to explore the therapeutic effect and underlying molecular mechanisms of morin in GC. METHODS: For in vitro experiments, the proliferation inhibition of morin was measured by cell counting kit-8 assay and colony formation assay in human GC cell line MKN45, human gastric adenocarcinoma cell line AGS, and human gastric epithelial cell line GES-1; for apoptosis analysis, microscopic photography, Western blotting, ubiquitination analysis, quantitative polymerase chain reaction analysis, flow cytometry, and RNA interference technology were employed. For in vivo studies, immunohistochemistry, biomedical analysis, and Western blotting were used to assess the efficacy and safety of morin in a xenograft mouse model of GC. RESULTS: Morin significantly inhibited the proliferation of GC cells MKN45 and AGS in a dose- and time-dependent manner, but did not inhibit human gastric epithelial cells GES-1. Only the caspase inhibitor Z-VAD-FMK was able to significantly reverse the inhibition of proliferation by morin in both GC cells, suggesting that apoptosis was the main type of cell death during the treatment. Morin induced intrinsic apoptosis in a dose-dependent manner in GC cells, which mainly relied on B cell leukemia/lymphoma 2 (BCL-2) associated agonist of cell death (BAD) but not phorbol-12-myristate-13-acetate-induced protein 1. The upregulation of BAD by morin was due to blocking the ubiquitination degradation of BAD, rather than the transcription regulation and the phosphorylation of BAD. Furthermore, the combination of morin and BCL-2 inhibitor navitoclax (also known as ABT-737) produced a synergistic inhibitory effect in GC cells through amplifying apoptotic signals. In addition, morin treatment significantly suppressed the growth of GC in vivo by upregulating BAD and the subsequent activation of its downstream apoptosis pathway. CONCLUSION Morin suppressed GC by inducing apoptosis, which was mainly due to blocking the ubiquitination-based degradation of the pro-apoptotic protein BAD. The combination of morin and the BCL-2 inhibitor ABT-737 synergistically amplified apoptotic signals in GC cells, which may overcome the drug resistance of the BCL-2 inhibitor. These findings indicated that morin was a potent and promising agent for GC treatment. Please cite this article as: Wang Y, Sun XY, Ma FQ, Ren MM, Zhao RH, Qin MM, Zhu XH, Xu Y, Cao ND, Chen YY, Dong TG, Pan YF, Zhao AG. Morin inhibits ubiquitination degradation of BCL-2 associated agonist of cell death and synergizes with BCL-2 inhibitor in gastric cancer cells. J Integr Med. 2025; 23(3): 320-332.
Humans ; Flavonoids/therapeutic use* ; Stomach Neoplasms/pathology* ; Animals ; Proto-Oncogene Proteins c-bcl-2/metabolism* ; Cell Line, Tumor ; Apoptosis/drug effects* ; Cell Proliferation/drug effects* ; Ubiquitination/drug effects* ; Mice ; Drug Synergism ; Mice, Inbred BALB C ; Mice, Nude ; Xenograft Model Antitumor Assays ; Flavones

Objective:To analyze the reoperation rate and causes during the early adoption phase of unilateral biportal endoscopy (UBE).Methods:The clinical data of 180 patients who underwent UBE performed by a single surgeon at Beijing Friendship Hospital, Capital Medical University from October 2021 to June 2023 were retrospectively analyzed. Clinical and imaging data of patients who underwent reoperation were collected to analyze the causes of reoperation, and the clinical efficacy of the reoperations was also followed up. Measurement data were expressed as mean ± standard deviation ( ± s), and t-test was used before and after treatment. Results:A total of 180 patients who underwent UBE were included in this study, of which 6 patients underwent reoperation, and the reoperation rate was 3.33%. Among them, 3 cases occurred in the first 90 surgeries and the other 3 occurred in the subsequent 90 surgeries. The causes of reoperation were as follows: recurrent lumbar disc herniation at the same segment postoperatively in 2 cases, insufficient decompression in 2 cases, disc herniation following isolated decompression in 1 case, and immediate postoperative perianal numbness in 1 case. The time between the initial surgery and reoperation ranged from 0 to 187 days, with an average of 63.3 days. The average follow-up time after reoperation was 18.3 months. The visual analogue scale (VAS) and Oswestry disability index (ODI) scores of the patients at the last follow-up were significantly improved compared with those before operation (VAS score of low back pain: 5.2 ± 1.7 before operation, 1.2 ± 0.8 at the last follow-up, P<0.001; VAS score of leg pain: 7.2 ± 1.5 before operation, 1.2 ± 1.2 at the last follow-up, P<0.001; ODI score: 67.3 ± 5.7 before operation, 20.2 ± 8.2 at the last follow-up, P<0.001). The postoperative modified MacNab scores were generally satisfactory (4 cases were rated as excellent, accounting for 66.7%; 2 cases were rated as good, accounting for 33.3%). Except for one patient who experienced dural injury during open revision surgery, there were no serious complications such as nerve damage. Conclusions:In the early stages of UBE surgery, recurrent lumbar disc herniation and inadequate decompression are the primary reasons for reoperation, typically occurring within the first three months postoperatively. Reoperation does not significantly increase the risk of nerve injury. Enhanced early postoperative follow-up is recommended. For symptomatic patients, a second surgery with thorough decompression can yield satisfactory treatment outcomes.