OBJECTIVES: To analyze the efficacy and safety of concomitant left atrial appendage clipping during heart valve surgery for valvular heart disease patients with atrial fibrillation. METHODS: Fifty-eight patients who underwent concomitant left atrial appendage clipping during cardiac valve surgery in the Second Affiliated Hospital of Nanchang University from January 2017 to June 2023 were included in the analysis, including 1 case who underwent aortic valve replacement, 49 cases who underwent mitral valve replace-ment (or valvuloplasty)+tricuspid valvuloplasty, and 8 cases who underwent double valve replacement+tricuspid valvuloplasty (3 cases combined with coronary artery bypass grafting). The patients were followed up for 3-36 months [(16.69±6.61) months] after operation, and the changes of cardiac function and the occurrence of serious adverse complications were evaluated. RESULTS: The cardiopulmonary bypass time ranged from 75 to 145 min [(102.50±21.03) min], and the aortic cross-clamp time ranged from 35 to 80 min [(58.02±14.63) min]. The length of postoperative intensive care unit stay was 1 to 5 days [(2.47±0.82) d], and the length of postoperative hospital stay was 7 to 22 days [(10.84±2.69) d]. Cardiac ultrasound indicated complete closure of the left atrial appendage in all cases. During the follow-up, New York Heart Association (NYHA) functional classifications were improved in 54 patients. No left atrial appendage-related bleeding events or other perioperative complications were observed; and no cerebral infarction, limb embolism events, or mortality cases occurred during the follow-up. CONCLUSIONS For valvular heart disease patients with atrial fibrillation, concomitant left atrial appendage clipping during cardiac valve surgery demonstrates efficacy and safety, with no severe adverse events during a medium-term follow-up.
Humans ; Atrial Appendage/surgery* ; Atrial Fibrillation/complications* ; Male ; Female ; Heart Valve Diseases/complications* ; Aged ; Middle Aged ; Heart Valve Prosthesis Implantation/methods* ; Treatment Outcome ; Cardiac Surgical Procedures/methods* ; Mitral Valve/surgery*

N6-Methyladenosine (m6A) modification is a crucial post-transcriptional regulatory mechanism and the most abundant and highly conserved RNA epigenetic modification in eukaryotes. Previous studies have indicated the involvement of m6A modification in various tissue regeneration processes, including liver regeneration. Vir-like m6A methyltransferase associated protein (VIRMA) is an m6A methyltransferase with robust methylation capability. However, its role in liver regeneration remains poorly understood. In this study, we generated liver-specific Virma knockout mice using the Cre-loxP system and investigated the biological functions of VIRMA in liver regeneration using both the Associating Liver Partition and Portal vein Ligation for Staged Hepatectomy (ALPPS) mouse model and the carbon tetrachloride (CCl₄) mouse model. The expression level of VIRMA was rapidly up-regulated after ALPPS surgery and gradually down-regulated during liver repair. Virma deficiency significantly impaired liver regeneration capacity and disrupted cell cycle progression. Methylated RNA immunoprecipitation sequencing (MeRIP-seq) analysis revealed that Shq1 is an effective downstream target of VIRMA-mediated m6A modification. The upregulation of Shq1 enhanced the proliferation ability of cells, which was attenuated by the specific AKT inhibitor ipatasertib. Supplementation of Shq1 in vivo alleviated the liver cell proliferation inhibition caused by Virma deficiency. Furthermore, the m6A-binding protein heterogeneous nuclear ribonucleoprotein a2b1 (HNRNPA2B1) enhanced the mRNA stability of Shq1. Mechanistically, Virma deficiency resulted in decreased m6A modification on Shq1 mRNA, leading to reduced binding ability of m6A-binding protein HNRNPA2B1 with Shq1, thereby decreasing the mRNA stability of Shq1 and reducing its protein expression level. Downregulation of Shq1 inhibited the PI3K/AKT pathway, thereby suppressing cell proliferation and cell cycle progression, ultimately impeding liver regeneration. In summary, our results demonstrate that VIRMA plays a critical role in promoting liver regeneration by regulating m6A modification, providing valuable insights into the epigenetic regulation during liver regeneration.

The acute combination fractures of the atlas and axis in adults have a higher rate of neurological injury and early death compared with atlas or axial fractures alone. Currently, the diagnosis and treatment choices of acute combination fractures of the atlas and axis in adults are controversial because of the lack of standards for implementation. Non-operative treatments have a high incidence of bone nonunion and complications, while surgeries may easily lead to the injury of the vertebral artery, spinal cord and nerve root. At present, there are no evidence-based Chinese guidelines for the diagnosis and treatment of acute combination fractures of the atlas and axis in adults. To provide orthopedic surgeons with the most up-to-date and effective information in treating acute combination fractures of the atlas and axis in adults, the Spinal Trauma Group of Orthopedic Branch of Chinese Medical Doctor Association organized experts in the field of spinal trauma to develop the Evidence-based guideline for clinical diagnosis and treatment of acute combination fractures of the atlas and axis in adults ( version 2023) by referring to the "Management of acute combination fractures of the atlas and axis in adults" published by American Association of Neurological Surgeons (AANS)/Congress of Neurological Surgeons (CNS) in 2013 and the relevant Chinese and English literatures. Ten recommendations were made concerning the radiological diagnosis, stability judgment, treatment rules, treatment options and complications based on medical evidence, aiming to provide a reference for the diagnosis and treatment of acute combination fractures of the atlas and axis in adults.

Objective:To investigate the safety of minimally invasive liver resection for resectable hepatocellular carcinoma (HCC) complicated with portal hypertension.Methods:The propensity score matching and retrospective cohort study was conducted. The clinicopathological data of 807 patients with resectable HCC who underwent minimally invasive liver resection in 8 medical centers, including Sir Run Run Shaw Hospital, Affiliated with the Zhejiang University School of Medicine et al, from June 2011 to November 2022 were collected. There were 670 males and 137 females, aged 58(50,66)years. Of the 807 patients, 173 cases with portal hypertension were divided into the portal hypertension group, and 634 cases without portal hypertension were divided into the non-portal hypertension group. Observation indicators: (1) propensity score matching and comparison of general data of patients between the two groups after matching; (2) intraoperative and post-operative situations; (3) subgroup analysis. Propensity score matching was done by the 1:1 nearest neighbor matching method, with the caliper setting as 0.001. Measurement data with skewed distribution were represented as M( Q1, Q3), and comparison between groups was conducted using the rank sum test. Count data were described as absolute numbers, and comparison between groups was conducted using the chi-square test or Fisher exact probability. Comparison of ordinal data was constructed using the non-parameter rank sun test. Results:(1) Propensity score matching and comparison of general data of patients between the two groups after matching. Of the 807 patients, 268 cases were successfully matched, including 134 cases in the portal hypertension group and 134 cases in the non-portal hypertension group. The elimination of the tumor diameter and robot-assisted surgery confounding bias ensured comparability between the two groups after propensity score matching. (2) Intraoperative and postoperative situations. The occlusion time of porta hepatis, cases with intraoperative blood transfusion, cases with postoperative complication, cases with complication >Ⅱ grade of Clavien-Dindo classification, cases of Clavien-Dindo classification as Ⅰ grade, Ⅱ grade, Ⅲ grade, Ⅳ grade, cases with liver related complication were 27.0(15.0,43.0)minutes, 33, 55, 15, 13, 29, 14, 1, 37 in the portal hypertension group, versus 35.0(22.0,60.0)minutes, 17, 25, 5, 14, 9, 4, 1, 13 in the non-portal hypertension group, showing significant differences in the above indicators between the two groups ( Z=-2.15, χ2=6.30, 16.39, 4.38, 20.72, 14.16, P<0.05). (3) Subgroup analysis. Results of subgroups analysis showed that in cases with major live resection, the operation time, volume of intraoperative blood loss, duration of postoperative hospital stay were 243.5(174.6,296.3)minutes, 200.0(150.0,600.0)mL, 7.5(6.0,13.0)days in the portal hypertension group, versus 270.0(180.0,314.5)minutes, 200.0 (75.0,450.0)mL, 7.0(5.5,10.0)days in the non-portal hypertension group, showing no significant difference in the above indicators between the two groups ( Z=-0.54, -1.73, -0.92, P>0.05). In cases with non-major live resection, the operation time, volume of intraoperative blood loss, duration of postoperative hospital stay were 170.0(120.0,227.5)minutes, 100.0(50.0,200.0)mL, 8.0(5.0,10.0)days in the portal hypertension group, versus 170.0(120.0,227.5)minutes, 100.0(50.0,200.0)mL, 7.0(5.5,9.0)days in the non-portal hypertension group, showing no significant difference in the above indicators between the two groups ( Z=-1.39, -0.10, 1.05, P>0.05). In cases with anatomical liver resection, the operation time, volume of intraoperative blood loss, duration of postoperative hospital stay were 210.0(150.0,285.0)minutes, 150.0(50.0,200.0)mL, 8.0(6.0,9.3)days in the portal hypertension group, versus 225.5(146.3,306.8)minutes, 100.0(50.0,250.0)mL, 7.0(6.0,9.0)days in the non-portal hypertension group, showing no significant difference in the above indica-tors between the two groups ( Z=-0.75, -0.26, -0.91, P>0.05). In cases with non-anatomical liver resection, the operation time, volume of intraoperative blood loss, duration of postoperative hospital stay were 173.5(120.0,231.5)minutes, 175.0(50.0,300.0)mL, 7.0(5.0,11.0)days in the portal hyper-tension group, versus 186.0(123.0,262.5)minutes, 100.0(50.0,200.0)mL, 7.0(5.0,9.5)days in the non-portal hypertension group, showing no significant difference in the above indicators between the two groups ( Z=-0.97, -1.12, -0.98, P>0.05). Conclusion:Minimally invasive liver resection or even major liver resection is safe and feasible for screened HCC patients complicated with portal hyper-tension, but attention should be paid to the prevention and treatment of postoperative complications.

Objective : To investigate the mechanism of AMD3100 reversing the resistance of human hepatocellular carcinoma cells to Sorafenib by regulating carbonic anhydrase IX ( CA9) and chemokine receptor 4 ( CXCR 4 ) . Methods : The Sorafenib resistant cell lines Huh7 / Sor and HepG2 / Sor were established from human hepatocellular carcinoma cells Huh7 and HepG2．The effects of Sorafenib alone or in combination with AMD3100 on the proliferation of Huh7，HepG2，Huh7 / Sor，HepG2 / Sor cells were detected．The difference of invasive ability between Sorafenib resistant cells and non-resistant cells，and the effect of AMD3100 on the invasive ability of hepatocellular carcinoma cells were observed．And the regulation effect of Sorafenib alone or in combination with AMD3100 on the expression of CA9 and CXCR4 proteins in Huh7，HepG2，Huh7 / Sor and HepG2 / Sor cells was detected. Results: Compared with the Control group，AMD3100 (50 μmol / L) increased the inhibitory effect of Sorafenib on the proliferation of Huh7 / Sor and HepG2 / Sor cells (P＜0．05) ．Compared with Huh7 cells，the invasive ability of Sorafenib resistant Huh7 / Sor cells was significantly enhanced (P＜0. 05) ，and AMD 3100 (50 μmol / L) decreased the invasive ability of Huh7 and Huh7 / Sor cells (P＜0．05) ．Compared with Huh7 and HepG2 cells，the protein expression of CA9 and CXCR4 in Huh7 / Sor and HepG2 / Sor cells increased (P＜0. 05) ．AMD3100 (50 μmol / L) down-regulated the protein expression of CA9 and CXCR4 in Huh7，HepG2，Huh7 / Sor and HepG2 / Sor cells (P ＜0. 05 ) . Conclusion AMD3100 can reduce the resistance of human hepatocellular carcinoma cells to Sorafenib by downregulating the expression of CA9 and CXCR4，and enhance the inhibition of Sorafenib on the proliferation and invasion of human hepatocellular carcinoma cells.

Objective To systematically evaluate the intervention effect of social psychological intervention on the health status of patients with bariatric surgery(BS).Methods 8 databases,including PubMed,PsycInfo,and Embase and Clinic Trials,were retrieved to recruit randomized controlled trials with computer from database establishing time to Sep.2022.Independent quality evaluation was conducted by 2 researchers,and Meta-analysis was performed by the RevMan5.3 software.Results Totally 23 RCTs were included.The meta-analysis showed that psychosocial interventions in BS patients improve emotional eating and binge eating behavior[SMD=-0.44,95％CI(-0.78,-0.09),P=0.010;MD=-5.88,95％CI(-8.65,-3.11),P＜0.001],promote better quality of life[SMD=0.30,95％CI(0.02,0.59),P=0.040]and physical mobility,alleviates anxiety and depression[SMD=-0.37,95％CI(-0.67,-0.08),P=0.010;SMD=-0.59,95％CI(-0.84,-0.33),P＜0.001].However,the effect on improving eating disorders[MD=-0.01,95％CI(-0.19,0.18),P=0.950]is not significant,and subgroup analysis results of different intervention measures and follow-up times showed that there was no statistically significant difference in weight changes between the social psychological intervention group and the control group.Conclusion Psychosocial intervention can effectively improve the mental state and eating behavior of the bariatric surgery patients,improve the quality of life and increase physical activity of patients.However,the effect of intervention on eating disorder and weight change is still unclear.More high-quality clinical studies need to be carried out for further verification.

Objective To investigate the effect of 810 nm low-level laser on neuronal axonal regeneration of mice with spinal cord injury and its related mechanism.Methods In vivo experiment:20 Balb/c mice were randomly divided into the spinal cord injury group(SCI group)and the 810 nm low-level laser irradiation group(low-level laser group)after spinal cord injury according to the random number table method,with each group containing ten mice.A mice SCI model was established through clamp injury and the low-level laser group continuously irradiated the damaged area with weak 810 nm low-level laser with selected parameters(continuous wave with wave length 810 nm,power density 2 mW/cm2,spot are 4.5 cm2,irradiation time 50 minutes,energy 6000J/cm2).Then immunofluorescence staining was used to observe the M1 macrophage marker-inducible nitric oxide synthase(iNOS),the M2 macrophage marker arginase 1(Arg-1)and the universal marker F4/80 of macrophages after 14 days.Furthermore,in the in vitro experiment,standardized low-level laser-macrophage irradiation model was established.Another 20 Balb/c mice were used to obtain primary bone marrow-derived macrophages which were induced into M1 macrophages using lipopolysaccharide(LPS)and interferon-gamma(INF-γ).The M1 macrophages were randomly divided into the M1 macrophage group(M1 group)and the low-level laser therapy group(M1 + low-level laser group)equally according to the random number table method.The M1 group was not treated,and the M1 + low-level laser group was treated with low-level laser of selected parameters.RT-qPCR and ELISA were used to detect the expression of interleukin-1 receptor antagonist(IL-1RA)and interleukin-10(IL-10)in M1 macrophages 24 hours after irradiation.Western blot was used to analyze the expression of iNOS,Arg-1,differentiation antigen cluster 206(CD206),protein kinase B(AKT),phosphorylated protein kinase B(p-AKT),cyclic adenosine response element binding protein(CREB)and phosphorylated cyclic adenosine response element binding protein(p-CREB)in M1 macrophages 48 hours after irradiation.Dorsal root gangtion neurons(DRG)were cultured in two groups of macrophage conditioned medium,and the length of DRG axon growth was measured 48 h later to evaluate the effect of low-level laser on neuronal axon growth.Results In the in vivo experiment,compared with mice with spinal cord injury alone,the fluorescence intensity of F4/80+ iNOS+ in the spinal cord injury area decreased(1.00±0.08vs. 0.06±0.04)(P＜ 0.05)and the fluorescence intensity of F4/80 + Arg-1 + increased after low-level laser(1.00±0.07vs.2.15±0.12)(P＜0.01).In the in vitro experiment,compared with the M1 group,the expression of the M1 macrophage marker iNOS in the M1 + low-level laser group decreased(1.00±0.11 vs.0.08±0.01)(P＜ 0.01);the M2 macrophage marker Arg-1(1.00±0.14vs.2.44±0.16)(P＜0.01),and the expression of CD206(1.00±0.12 vs.1.83±0.05)(P＜0.01)increased.In addition,IL-1RA expression was increased in the M1 + low-level laser group compared with the M1 group(RT-qPCR:1.00±0.00vs.2.27±0.22)(P＜0.01)(ELISA:1435.58±100.48vs.2006.12±123.91(P＜0.05);IL-10 expression was also increased in the M1 +low-level laser group compared with the M1 group(RT-qPCR:1.00±0.00 vs. 3.45±0,56)(P＜0.05)(ELISA:137.13±4.20 vs.188.29±8.49)(P＜ 0,01);compared with the M1 group,the macrophage polarization pathway protein in the M1 + low-level laser group increased,AKT(1.07±0.12vs.1.74±0.04)(P＜0.01),p-AKT(1.00±0.12 vs.1.64±0.15)(P＜0.05),p-CREB(1.00±0.10vs.2.12±0.18)(P＜0.01).Compared with the M1 group,the conditioned medium of the M1 + low-level laser group significantly promoted DRG axon growth(567.66±63.59 vs.1068.95±130.14)(P＜ 0,05).Conclusions The 810 nm low-level laser irradiation can promote neuronal axon regeneration of mice with spinal cord injury,which may be related to the regulation of macrophage polarization phenotype by low-level laser through AKT/CREB pathway.

Objective To investigate the expression of IL-10 in serum of patients with type 2 diabetic mellitus (T2DM) and its relationship with carotid atherosclerosis.Methods Totally 168 cases of T2DM patients treated in our hospital from May 2013 to December 2016 were retrospectively analyzed.According to the IMT value,the patients were divided into the normal group,the thickening of the group and carotid atherosclerosis plaque formation group.In addition,65 cases of healthy volunteers in our hospital physical examination center at the same period were treated as control group.The levels of serum inflammation index,blood glucose,blood lipid and other indicators of all subjects were compared,at the same time,the correlation between IL-10 and other detection index was analyzed.Additionally,the risk factors of T2DM patients with carotid atherosclerosis were analyzed.Results Compared with the control group,the levels of IL-6,blood glucose,blood lipid and other indicators in T2DM patients increased significantly(P＜0.05),while the level of IL-10 decreased significantly(P＜0.05);with the increase of IMT,the levels of IL-6,blood glucose,blood lipid and other indicators in T2DM patients increased significantly,but the level of IL-10 decreased significantly,meanwhile the differences between the groups were statistically significant (P＜0.05).Compared with normal group,the levels of IL-6,blood glucose,blood lipid and other indicators of patients in thickening group and plaque group significantly elevated,but the level of IL-10 decreased significantly;the levels of IL-6,blood glucose,blood lipid and other indicators of patients in plaque group were obviously higher than those of thickening group,and IL-10 level was significantly lower than thickening group,and the differences were statistically significant (P＜0.05);the levels of IL-10 in the serum were negatively correlated with blood glucose,blood lipid and other indicators (P＜0.05);multifactor non-conditional Logistic analysis showed that IL-6,Hcy and UA were the risk factors for atherosclerosis in T2DM patients,and IL-10 was the protective factor.Conclusion The level of IL-10 of patients with T2DM is closely related to the occurrence and development of carotid artery atherosclerosis,which provides a new target for clinical treatment.

Objective To investigate the role of bone marrow mesenchymal stem cells (BM-MSCs) in the invasion and metastasis of gastric cancer cells and to explore its mechanism.Methods SGC7901 and KATO-Ⅲ gastric cancer cells were co-cultured with BM-MSCs respectively,and the invasion ability of SGC7901 and KATO-Ⅲ gastric cancer cells were detected by Transwell assay.Secondly,CD133 + and CD133-cells were sorted from KATO-Ⅲ gastric cancers and co-cultured with BM-MSCs respectively to compare their changes in invasiveness.Meanwhile,the expressions of p-AKT and epithelial-mesenchymal transition (EMT) relative factors in gastric cancer cells were detected by Western-blot.The role of CD133 in BM-MSCs affecting the ability of invasion of gastric cancer cells was further vertified by the overexpression of CD133 in SGC7901 cells.SPSS17.0 software was used for statistical processing,and the stand deviation of the measurement data were expressed as the standard deviation,independent sample t test was conducted.Results The invasiveness of co-cultured SGC7901 and KATO-Ⅲ cells was significantly enhanced.The invasive ability of KATO-Ⅲ CD133+ cells co-cultured with BM-MSCs tended to increase more significantly than that of co-cultured CD133 cells[(259.0 ± 24.0)vs (58.0 ±5.6),P ＜ 0.001].The expressions of p-AKT,Snail and N-cadherin were significantly increased in co-cultured CD133+ cells (P =0.003,P =0.003,P =0.002),while the expression of E-cadherin was reduced (P =0.021).After co-cultured with BM-MSCs,the expression of E-cadherin was also reduced in CD133-cells (P =0.005),but the expressions of p-AKT,Snail and N-cadherin were no significantly changes (P =0.744,P =0.277,P =0.295).SGC7901 co-cultured with BM-MSC after overexpression of CD133 showed higher i nvasiveness than blank control group[(239.3 ± 24.0) vs (103.3 ± 15.5),P ＜ 0.001].The expressions of p-AKT,Snail and N-cadherin were significantly increased when co-cultured with BM-MSCs in the group of CD133 overexpression (P =0.001,P =0.001,P =0.001),while the expression of E-cadherin was significantly decreased(P =0.003).The expressions of Snail and N-cadherin were also significantly increased after co-cultured with BM-MSCs in the blank control group (P =0.001,P =0.004),and the expression of E-cadherin was significantly decreased (P =0.018),while the expression of p-AKT was not significantly changed (P =0.193).Conclusions BM-MSCs can enhance the invasion and metastasis of gastric cancer cells by promoting the EMT of gastric cancer cells.CD133 may be involved in the regulation of EMT in gastric cancer cells through the PI3K/AKT signaling pathway.

Based on thorough analysis of the present healthcare big data,and present problems found in precision medicine,the paper proposed the implementation approach of precision medicine driven by healthcare big data.Citing the practice of the hospital as an example,the authors centered on clinical data to build a precision medicine knowledge system,and leveraged in-depth data mining to develop integrated analysis technology for precision medicine.These efforts aim at application development of precision medicine series upon a panoramic medicine knowledge display,so as to enhance medical quality and diagnosis efficiency and translated use of healthcare big data in precision medicine.