Objective To explore the mechanisms of Buyang Huanwu Decoction(BYHWD)in reducing oxidative stress levels to protect the blood-brain barrier(BBB)in cerebral ischemia/reperfusion injury(CIRI)rats.Methods A middle cerebral artery occlusion/reperfusion(MCAO/R)model in rats was established via wire embolization method.PeriCam PSI laser speckle flow imaging was applied to detect whether the model was successfully established.Neurological deficits in the rats were evaluated by Zea Longa score,and histopathological changes in the rat brain were observed by HE staining.The degree of brain edema was detected by the dry and wet weight method.BBB permeability was detected by Evans blue staining,and ultrastructural changes to the BBB were observed by transmission electron microscopy.The levels of ROS,MDA and SOD activities,which are related to oxidative stress,were detected using kits.The expression levels of matrix metalloproteinase-9(MMP-9)were detected by immunohistochemical staining and Western blot.The expression levels of Occludin,ZO-1,and Claudin-5 tight junction proteins were determined via immunofluorescence and Western blot.Results BYHWD reduced neurological deficit scores,alleviated brain histopathological damage,alleviated BBB structural disruption,prolonged the appearance of dense regions in the tight junction structure,attenuated edema of the brain on the ischemic side,and reduced BBB permeability in MCAO/R rats.BYHWD decreased the levels of ROS and MDA,increased the activity of SOD,decreased the expression levels of MMP-9,and increased the expression levels of Occludin,Claudin-5 and ZO-1.Conclusions BYHWD can increase BBB tight junction protein expression levels,reduce the permeability of the BBB,protect the ultrastructure of the BBB,and reduce brain edema,and its mechanisms may be related to its antioxidant activity and inhibition of MMP-9 activation.

[Objective]To identify the relationship between tumor tissue interleukins(ILs)and non-small cell lung cancer(NSCLC)patients with poor response to immune checkpoint blockade(ICB)therapy,and to investigate the differ-ential expression of ILs in tumor of NSCLC patients as well as its effect on ICB response and prognosis.[Methods]A total of 61 patients diagnosed with NSCLC and treated with ICB were retrospectively collected from the data of a previous study.We obtained transcriptome sequencing data from tumor tissues and survival data of the patients before ICB treatment.Us-ing bioinformatics methods,we screened for ILs that significantly affected the efficacy and prognosis of ICB treatment.We evaluated the efficacy of ICB treatment using progressive-free survival(PFS)and assessed the prognosis using overall sur-vival(OS).The Kaplan-Meier survival curve and ROC curve were used to analyze the predictive effect and efficacy of ILs on the efficacy and prognosis of ICB in NSCLC patients.[Results]The results of the univariate Cox regression analysis in our study showed that nine ILs were found to be associated with OS of NSCLC patients treated with ICB at a significance level of P<0.1.Further multivariate analysis revealed that high expression of IL-11,IL-17D,and IL-36A was significant-ly associated with poor prognosis in these patients(P<0.05).The results from the Kaplan-Meier survival curve analysis revealed a significant negative correlation between the high expression of IL-17D and both PFS and OS in NSCLC patients.Specifically,patients with IL-17D high expression had a median PFS of 3.1 months compared with 6.5 months in low ex-pression patients[95%confidence interval(CI)(1.178,3.655),P=0.009].Similarly,the median OS was 9.8 months in the high expression group versus 21.8 months in the low expression group[95%CI(1.116,4.392),P=0.018].ROC curve showed that the prediction performance was favorable[AUCPFS=0.702,95%CI(0.562,0.842),P=0.027;AU-COS=0.684,95%CI(0.550,0.818),P=0.014].Although IL-11 and IL-36A alone were not significant predictors of PFS and OS in NSCLC patients,the median PFS and OS were notably shortened to 2.2 months(P=0.003)and 3.0 months(P<0.001),respectively,when high expression of IL-11 and IL-36A was combined with high expression of IL-17D.The ROC curve analysis demonstrated an improvement in prediction efficiency for both PFS and OS in NSCLC patients[AUCPFS=0.748,95%CI(0.615,0.880),P=0.007;AUCOS=0.703,95%CI(0.573,0.833),P=0.007].[Conclu-sion]The results suggest that high expression of IL-11,IL-17D,and IL-36A is associated with a higher risk of disease progression which correlates to poor PFS and OS in NSCLC patients.

Objective: To explore the correlation between Diabetes Complication Severity Index(DCSI), C-reactive protein/albumin ratio(CAR) and death in patients with diabetic foot ulcer(DFU) and to clarify their predictive value for all-cause death in DFU patients. Methods: Retrospectively analyzed the clinical data of 354 DFU patients who were treated in the Endocrinology Department of the First Affiliated Hospital of Anhui Medical University from July 2019 to December 2022. Based on survival status during follow-up, patients were divided into a survival group(n=268) and a death group(n=86). Univariate and multivariate Cox regression analyses were used to identify risk factors for all-cause death in DFU patients. Receiver operating characteristic(ROC) curves were plotted to evaluate the predictive value of DCSI, CAR, and their combination for all-cause death in DFU patients. Kaplan-Meier curves were used to explore the impact of different DCSI and CAR levels on survival in DFU patients. Results: Univariate Cox regression analysis showed that older age, history of hypertension, higher Wagner classification levels, and elevated levels of CRP, Scr, FDP, DCSI score, and CAR were associated with a higher risk of death in DFU patients(P<0.05). Higher levels of HGB, HCT, ALB, or eGFR were associated with a lower risk of death. Patients receiving combined insulin and oral hypoglycemic medication had a lower risk of death compared to those receiving only insulin therapy(P<0.05). Multivariate Cox regression analysis indicated that older age, higher levels of Scr, DCSI, and CAR were independent risk factors for all-cause death in DFU patients, while higher levels of ALB and combined insulin and oral hypoglycemic therapy were protective factors. ROC curve analysis showed that the AUC values for DCSI, CAR, and their combination were 0.652, 0.633, and 0.686, respectively. Kaplan-Meier curve analysis revealed that patients with high DCSI scores(≥4.5) had a lower survival rate compared to those with lower DCSI scores(<4.5). Similarly, patients with high CAR levels(≥0.124) had a lower survival rate compared to those with lower CAR levels(<0.124). Conclusion High levels of DCSI and CAR are independent risk factors for all-cause death in DFU patients. DCSI, CAR, and their combination have predictive value for all-cause mortality in DFU patients.

Objective: To compare the efficacy and safety of combining diosmin with Jiuhua hemorrhoid suppository versus diosmin alone for the treatment of hemorrhoid hemorrhage. Methods: The Jiuhua hemorrhoid suppository study was conducted in 10 medical centers across China from April 1, 2019 to June 30, 2020. Patients with hemorrhoid bleeding were randomized in a ratio of 1 : 1 to either receive Jiuhua hemorrhoid suppository and diosmin tablets (the study group) or diosmin tablets alone (the control group). The suppository was used once a day after defecation or at bedtime after rinsing the anus with warm water. Diosmin tablets were administered only once a day (0.9 g). The primary endpoint of the study was the assessment of hemorrhoid bleeding relief 7 ± 2 days after treatment, classified as “very effective” “effective” and “ineffective”. The secondary endpoint included the evaluation of pain alleviation using the visual analogue scale (VAS, with scores ranging from 0 to 10) and edema (with scores ranging from 0 to 3). The safety of the two treatment regimens was evaluated 14 ± 2 days after drug administration. Results: The full analysis set (FAS) comprised 107 participants in the study group and 111 in the control group, while the per-protocol set (PPS) included 106 participants in the study group and 111 in the control group. In terms of hemorrhoid bleeding, the proportion of very effective and effective cases in the study group were significantly higher than that in the control group [106 (99.06%) vs. 91 (81.98%), P < 0.0001] in the FAS, and the PPS results [105 (99.06%) vs. 91 (81.98%), P < 0.0001] were comparable to the FAS results. The pain VAS scores at day 7 after treatment were comparable between the two groups (0.80 ± 1.17 vs. 0.80 ± 1.20, P = 0.2177). The majority of the participants in both groups had an edema score of 0 at day 7 after treatment [96 (89.72%) vs. 99 (91.67%), P = 0.370 5]. Adverse events (AEs) occurred in 9 patients (8.4%) in the study group and 3 patients (2.7%) in the control group. In addition, 5 AEs in the study group and 1 AE in the control group were possibly in association with the study drug. Conclusion Compared with the administration of diosmin oral tablets alone, the addition of Jiuhua hemorrhoid suppository to the tablets demonstrates enhanced efficacy in addressing hemorrhoid bleeding, with satisfactory patient adherence and acceptable safety.

The Gastroesophageal reflux disease(GERD)is related to the dynamic disorder of the digestive tract caused by the imbalance of the viscera and meridians.The spleen and stomach are the hub of the qi machinery,transforming the essence of water and valley into energy and regulating the Yin and Yang of all bodies.The sympathetic balance between Ren-Du and Qi is the motivity of the spleen and stomach.Interstitial cells of Cajal(ICC)are the hub of digestive motility,which can maintain mitochondrial energy metabolism through mitochondrial autophagy and improve the digestive motility.Therefore,in this paper,the molecular biological basis of GERD was discussed based on the"regulating pivot with pivot"theory that the pivots of viscera and meridians drive ICC mitochondrial energy balance.It also explains the feasibility of Qi-Shi-Sheng-Jiang-Gui-Yuan Decoction in treating GERD based on"regulating pivot with pivot",which is helpful to realize the microscopization and concretization of"regulating pivot with pivot"theory and realize the modernization of TCM theory.

Transcatheter tricuspid valve intervention is the new frontier of interventional cardiology. The LuX-Valve is a radial force-independent orthotopic tricuspid valve replacement device developed in China. The LuX-Valve Plus transcatheter tricuspid valve replacement (TTVR) system is changed from the trans-atrial to the transjugular approach, which further reduces trauma and pulmonary complications compared with the first generation LuX-Valve. The first-in-human study has been completed at Zhongshan Hospital, Fudan University and an exploratory multicentre clinical study is underway. Echocardiography plays an important role in pre-TTVR screening, intraoperative guidance and postoperative evaluation and follow-up, especially two-dimensional transoesophageal echocardiography (2D-TEE) and three-dimensional transoesophageal echocardiography (3D-TEE). However, there is a lack of appropriate intraoperative guidance and assessment protocols. In this study, we briefly described the protocols and imaging considerations for intraoperative 2D-TEE and 3D-TEE to ensure the successful implantation of TTVR.

Tricuspid regurgitation (TR) interventions are under rapid development. The K-Clip? system is the first domestic transcatheter tricuspid annuloplasty system with unique clamping procedure to achieve annular reduction.Intraoperative echocardiographic monitoring procedures for transcatheter tricuspid annuloplasty have not been reported yet in China. Thus, this review aimed to propose the standard two-dimensional and three-dimensional transesophageal echocardiographic workplanes and procedures to guide and monitor the implantation of K-Clip system based on our experience in Zhongshan Hospital, Fudan University to provide a reference point for the intraoperative echocardiographic monitoring of future transcatheter tricuspid annuloplasty devices in China.

Objective:To investigate the association between Onodera's prognostic nutritional index (OPNI) and postoperative adverse outcomes in elderly gastrointestinal surgery patients and assess the predictive value.Methods:A total of 230 elderly patients who received gastrointestinal surgery were prospectively enrolled. Clinical data, including age, sex, preoperative laboratory parameters, surgery process and clinical outcomes, were collected. The optimal cut-off value of OPNI was obtained using NRS 2002, a well-recognized nutritional risk screening tool, as the standard. The associations of OPNI, geriatric nutritional risk index (GNRI) and albumin with in-hospital mortality, complication incidence and duration of postoperative hospital stay were evaluated using Chi-square test or nonparametric test as appropriate. Confounders were identified through univariate analysis and logistic and linear regression models were developed to validate the correlation and assess the predictive value of OPNI for postoperative clinical outcomes.Results:The optimal cut-off value for the OPNI was 41.25, which yielded a sensitivity of 72.7% and a specificity of 59.9% with area under the curve (AUC) at 0.682. The incidence of OPNI-based malnutrition (defined as OPNI < 41.25) was 50% (115/230). Univariate analysis indicated that patients with OPNI < 41.25 had a significantly higher mortality (8.70% versus 2.61%, P = 0.046) and complication incidence (20.00% versus 9.57%, P = 0.026) and significantly longer postoperative hospital stay (11.17 d versus 8.49 d, P = 0.009) than patients with OPNI ≥ 41.25. Patients with GNRI < 98 had a longer postoperative hospital stay than those with GNRI ≥ 98 (10.71 d versus 7.55 d, P = 0.001) while there was no significant difference in mortality or complication incidence between the two groups ( P > 0.05). As for subgroups divided according to albumin levels (< 35 g/L or ≥35 g/L), no significant differences in mortality, postoperative complications incidence, or duration of postoperative hospital stay were observed ( P > 0.05). Multivariate analysis verified that OPNI < 41.25 was an independent risk factor for the development of postoperative complications ( OR: 2.660, 95% CI: 1.079-6.557, P = 0.034) and prolonged postoperative hospital stay ( R2 = 0.135, regression coefficient = 2.73, P = 0.047), where the AUC of the regression model for complications was 0.812 (95% CI: 0.741-0.882). GNRI < 98 was the independent risk factor for prolonged postoperative hospital stay ( R2 = 0.134, regression coefficient = 2.797, P = 0.049). Conclusion:OPNI is an independent risk factor for adverse clinical outcomes after gastrointestinal surgery in elderly patients and demonstrates good predictive value with the cut-off value of 41.25.

[摘 要] 目的：探究微小RNA-504（miRNA-504）在胃癌（GC）组织中的表达水平及其对GC细胞生物学行为的调控机制。方法：收集2020年6月至2020年12月期间三亚中心医院外科收治的48例胃癌患者的肿瘤组织及癌旁组织标本，qPCR检测组织中miR-504、肿瘤蛋白53诱导型核蛋白1（tumor protein 53-induced nuclear protein 1，TP53INP1）mRNA的水平，WB法检测TP53INP1水平。体外培养人胃癌细胞BGC-823，分为对照组（正常培养的BGC-823细胞）、miR-504 mimic组、mimic-NC组、miR-504 inhibitor组、inhibitor-NC组、miR-504 inhibitor+si-NC组、miR-504 inhibitor+si-TP53INP1组，qPCR检测细胞中miR-504和TP53INP1 mRNA的表达，MTT法、流式细胞术、划痕实验和Transwell侵袭实验分别检测各组细胞的增殖、凋亡、迁移和侵袭能力，WB法检测各组细胞中增殖、迁移和侵袭相关蛋白（Cyclin D1、E-cadherin、MMP-2、MMP-9）以及TP53INP1的表达。双荧光素酶报告基因实验进一步验证miR-504与TP53INP1 mRNA的靶向关系。结果：与癌旁组织相比，胃癌组织中miR-504的表达显著升高（P<0.05），而TP53INP1 mRNA和蛋白表达水平显著降低（P<0.05或P<0.01），miR-504和TP53INP mRNA两者的表达呈负相关（P<0.01）。与对照组相比，miR-504 mimic组BGC-823细胞中miR-504的表达显著升高（P<0.05）、TP53INP1 mRNA和蛋白的表达显著降低（均P<0.05），且细胞增殖率、划痕愈合率、侵袭入Transwell小室下层的细胞数量，Cyclin D1、MMP-2、MMP-9蛋白表达均显著增加，细胞凋亡率和E-cadherin蛋白表达均显著降低（均P<0.05）。转染miR-504 inhibitor能显著下调BGC-823中miR-504的表达、上调TP53INP1 mRNA和蛋白的表达，抑制细胞的增殖、迁移与侵袭能力而促进细胞凋亡（均P<0.05）；而下调TP53INP1的表达可明显减弱miR-504下调对BGC-823细胞增殖、迁移与侵袭的抑制作用（P<0.01）。miR-504高表达能明显抑制野生型TP53INP1质粒的荧光素酶活性（P<0.05）。结论：miR-504在胃癌组织中呈高表达，下调miR-504可抑制胃癌BGC-823细胞的恶性生物学行为而促进其凋亡，其作用机制可能与靶向调控TP53INP1的表达有关。

Objective To compare in-vitro percutaneous absorption and pharmacodynamic actions of anti-inflammation and inhibiting delayed-type hypersensitivity of Chinese herbal compound cremor for eczema (CHCCE) with different mass concentrations of synthetic borneol. Methods By adopting modified Franz diffusion device add with isolated BALB/cnude mice skin as a barrier, in vitro percutaneous absorption effectiveness of CHCCE with different mass concentrations of borneol was compared by in vitro percutaneous test after the content of matrine was determined with high performance liquid chromatography(HPLC). Meanwhile, the effects of CHCCE with different mass concentrations of synthetic borneol on reducing dimethylbenzene-induced auricular edema and suppressing delayed-type hypersensitivity induced by 2,4-dinitrochlorobenzene(DNCB) in mice were compared. Results Cumulative permeation amount of matrine in CHCCE with synthetic borneol was higher than that in CHCCE without synthetic borneol 2～ 48 h after administration (P < 0.05). There was no significant difference of cumulative permeation amount (P>0.05) among CHCCE groups with different mass concentrations of synthetic borneol after 48 h. In vitro percutaneous absorption behavior of matrine arrived to the steady state and the cumulative permeation amount of matrine presented a decreasing trend in all medication groups 12 h after administration. Within 12 h of the medication, the permeation rate of CHCCE with different mass concentrations of borneol was in the sequence of 3％ borneol > 1％ borneol > 2％ borneol > 0.5％ borneol > no borneol. The content of matrine was decreased with the increase of mass concentration of synthetic borneol after 12 h. The results of pharmacodynamic actions of CHCCE showed that compared with the blank control group, CHCCE with 1％, 3％ synthetic borneol could significantly suppress the acute inflammation induced by dimethylbenzene and inhibit contact dermatitis induced by dinitrochlorobenzene (DNCB) in mice(P < 0.05). Compared with Triamcinolone Acetonide Acetate and Miconazole Nitrate and Neomycin Sulfate Cream, CHCCE with 1％, 3％synthetic borneol could decrease the serum level of IL-4, but the difference was insignificant(P>0.05). Conclusion CHCCE with 1％ synthetic borneol has good effects on in vitro transdermal absorption, and can suppress inflammation and delayed-type hypersensitivity effectively.