Background: s/Aims: Non-invasive models stratifying clinically significant portal hypertension (CSPH) are limited. Herein, we developed a new non-invasive model for predicting CSPH in patients with compensated cirrhosis and investigated whether carvedilol can prevent hepatic decompensation in patients with high-risk CSPH stratified using the new model. Methods: Non-invasive risk factors of CSPH were identified via systematic review and meta-analysis of studies involving patients with hepatic venous pressure gradient (HVPG). A new non-invasive model was validated for various performance aspects in three cohorts, i.e., a multicenter HVPG cohort, a follow-up cohort, and a carvediloltreating cohort. Results: In the meta-analysis with six studies (n=819), liver stiffness measurement and platelet count were identified as independent risk factors for CSPH and were used to develop the new “CSPH risk” model. In the HVPG cohort (n=151), the new model accurately predicted CSPH with cutoff values of 0 and –0.68 for ruling in and out CSPH, respectively. In the follow-up cohort (n=1,102), the cumulative incidences of decompensation events significantly differed using the cutoff values of <–0.68 (low-risk), –0.68 to 0 (medium-risk), and >0 (high-risk). In the carvediloltreated cohort, patients with high-risk CSPH treated with carvedilol (n=81) had lower rates of decompensation events than non-selective beta-blockers untreated patients with high-risk CSPH (n=613 before propensity score matching [PSM], n=162 after PSM). Conclusions Treatment with carvedilol significantly reduces the risk of hepatic decompensation in patients with high-risk CSPH stratified by the new model.

Background: s/Aims: Non-invasive models stratifying clinically significant portal hypertension (CSPH) are limited. Herein, we developed a new non-invasive model for predicting CSPH in patients with compensated cirrhosis and investigated whether carvedilol can prevent hepatic decompensation in patients with high-risk CSPH stratified using the new model. Methods: Non-invasive risk factors of CSPH were identified via systematic review and meta-analysis of studies involving patients with hepatic venous pressure gradient (HVPG). A new non-invasive model was validated for various performance aspects in three cohorts, i.e., a multicenter HVPG cohort, a follow-up cohort, and a carvediloltreating cohort. Results: In the meta-analysis with six studies (n=819), liver stiffness measurement and platelet count were identified as independent risk factors for CSPH and were used to develop the new “CSPH risk” model. In the HVPG cohort (n=151), the new model accurately predicted CSPH with cutoff values of 0 and –0.68 for ruling in and out CSPH, respectively. In the follow-up cohort (n=1,102), the cumulative incidences of decompensation events significantly differed using the cutoff values of <–0.68 (low-risk), –0.68 to 0 (medium-risk), and >0 (high-risk). In the carvediloltreated cohort, patients with high-risk CSPH treated with carvedilol (n=81) had lower rates of decompensation events than non-selective beta-blockers untreated patients with high-risk CSPH (n=613 before propensity score matching [PSM], n=162 after PSM). Conclusions Treatment with carvedilol significantly reduces the risk of hepatic decompensation in patients with high-risk CSPH stratified by the new model.

Background: s/Aims: Non-invasive models stratifying clinically significant portal hypertension (CSPH) are limited. Herein, we developed a new non-invasive model for predicting CSPH in patients with compensated cirrhosis and investigated whether carvedilol can prevent hepatic decompensation in patients with high-risk CSPH stratified using the new model. Methods: Non-invasive risk factors of CSPH were identified via systematic review and meta-analysis of studies involving patients with hepatic venous pressure gradient (HVPG). A new non-invasive model was validated for various performance aspects in three cohorts, i.e., a multicenter HVPG cohort, a follow-up cohort, and a carvediloltreating cohort. Results: In the meta-analysis with six studies (n=819), liver stiffness measurement and platelet count were identified as independent risk factors for CSPH and were used to develop the new “CSPH risk” model. In the HVPG cohort (n=151), the new model accurately predicted CSPH with cutoff values of 0 and –0.68 for ruling in and out CSPH, respectively. In the follow-up cohort (n=1,102), the cumulative incidences of decompensation events significantly differed using the cutoff values of <–0.68 (low-risk), –0.68 to 0 (medium-risk), and >0 (high-risk). In the carvediloltreated cohort, patients with high-risk CSPH treated with carvedilol (n=81) had lower rates of decompensation events than non-selective beta-blockers untreated patients with high-risk CSPH (n=613 before propensity score matching [PSM], n=162 after PSM). Conclusions Treatment with carvedilol significantly reduces the risk of hepatic decompensation in patients with high-risk CSPH stratified by the new model.

Aim To analyze serum exosome sequencing data from patients with coronary heart disease(CHD)and normal subjects by using bioinformatics-related methods to construct a competitive endogenous ln-cRNA-miRNA-mRNA(ceRNA)regulatory network,to mine the predicted potential Chinese medicines,and to perform preliminary validation of the biological processes and core Chinese medicines involved in the ceRNA network.Methods We used exoRbase data-base to obtain the expression matrix of differential genes,combined with the raw letter method to con-struct the ceRNA network,and performed GO analysis and KEGG analysis on the differential mRNAs in the network,and used COREMINE database to predict the biological processes and core target genes involved in the ceRNA network,and to screen the herbal medi-cines with potential therapeutic effects;AVECs oxida-tive damage cell model was constructed in vitro,and the cytoskeleton,tube-forming function,cell prolifera-tion,LDH leakage rate,ROS level and p-AKT,AKT,p-PI3K and AKT protein expression were examined to verify the action pathways and targets of the core Chi-nese medicine Salvia miltiorrhiza for the treatment of coronary heart disease.Results Compared with nor-mal subjects,395 mRNAs,80 miRNAs,60 lncRNA differential genes,and 80 miRNAs were predicted in serum exosomes of coronary heart disease,and the constructed ceRNA sub-network,mainly consisted of 21 lncRNAs,80 miRNAs,and 82 mRNAs;AKT1,VEGFA,IL1B and other genes in the network.The abnormally expressed mRNAs were involved in biologi-cal processes such as oxidative stress and signaling pathways such as PI3 K/Akt,and Dan Shen,Chuanx-iong and Panax notoginseng were most closely related to exosome-mediated biological processes and core genes in coronary heart disease.The active ingredients of tanshinone ⅡA,the core Chinese medicine,could pro-mote vascular endothelial cell proliferation,tube for-mation,skeleton formation and repair,reduce LDH leakage rate and ROS level,and promote the expres-sion of p-AKT and p-PI3K protein.Conclusion There is a complex ceRNA regulatory network trans-duction in coronary artery disease serum exosomes,and traditional Chinese medicine can be used to treat CHD through multi-target intervention,and Dan Shen,Chuanxiong and Panax notoginseng are expected to be candidate sources of traditional Chinese medicine,a-mong which the active ingredient of Dan Shen,tanshi-none ⅡA,activates PI3 K/Akt signaling pathway to play a protective role against oxidative stress-injured cells,and treats CHD.

Aim To study the effect of emetine on in-sulin secretion through glucagon-like peptide-1 receptor(GLP-1R).Methods Isolating rat islets were used to carry out insulin secretion experiment.Islets were incubated with different concentrations of emetine(2,10,50 μmol·L-1),different concentrations of glu-cose solution(2.8,11.1,16.7 mmol·L-1)or spe-cific GLP-1R antagonist Exendin(9-39).The amount of insulin secretion in the supernatant of each group was determined by an enzyme-linked radioimmunoas-say.Small molecule compounds were docked to GLP-1R(PDB code:5NX2)using SYBYL-X2.0 software.Results Emetine could promote insulin secretion in high glucose(11.1 mmol·L-1)in a dose-dependent manner.In low glucose(2.8 mmol·L-1),insulin secretion did not change after intervention of emetine.But in high glucose(11.1,16.7 mmol·L-1),insu-lin secretion significantly increased under the treatment of emetine in a glucose-dependent manner.The doc-king score of emetine and GLP-1R was Total Score=6.82,C Score=5,indicating that emetine had a good binding affinity with GLP-1R.Using Exendin(9-39)to block GLP-1R,the insulinotropic effect of emetine was reduced.Conclusion Emetine could promote in-sulin secretion,which is related to the activation of GLP-1R.

Objective:To explore the mechanism of hepatitis B virus(HBV)inhibiting M1 macrophages to promote immune escape,and to provide targets and strategies for antiviral therapy.Methods:The human monocyte cell line THP-1 was induced into M1 macrophages with PMA+LPS+IFN-γ.Cell morphological changes and the expressions of CD68,CD86,HLA-DR and functional molecules IL-1β,IL-6,TNF-α in M1 macrophages were detected by flow cytometry and RT-qPCR to identify M1 macrophages.HBV stable replication cell line HepG2.2.15 were co-cultured with M1 macrophages,and the expression of HBV-DNA was detected by qP-CR.The expression of CD68,CD86 and HLA-DR were detected by flow cytometry.The expressions of functional molecules TLR4,NLRP3,Caspase-1,pro-caspase-1,caspase-1 p20,IL-1β and IL-18 in M1 macrophages were determined by RT-qPCR and Western blot.Apoptosis rate was detected by flow cytometry,and the expression of apoptosis related protein cleaved-caspase-3 was determined by Western blot.Results:THP-1 was successfully induced to differentiate into M1 macrophages.M1 macrophages inhibited HBV repli-cation(P<0.05).HBV inhibited the expressions of CD68,CD86 and HLA-DR in M1 macrophages(P<0.01).HBV inhibited the ex-pressions of TLR4,NLRP3,Caspase-1,caspase-1 p20,IL-1β and IL-18 in M1 macrophages(P<0.01).HBV induced M1 macro-phage apoptosis(P<0.05).Conclusion:HBV inhibits M1 macrophages and their functional molecules TLR4,NLRP3 and down-stream factors,reduces the synthesis and secretion of inflammatory factors,induces apoptosis,and then promotes immune escape,re-sulting in the persistence and replication of HBV in the body.

AIM To explore the ameliorative effects of Ziyin Mingmu Pills on mouse retinitis pigmentosa(RP)and the possible mechanism.METHODS The RP transgenic mice(rd10)were randomly divided into the model group,the Leding group(0.15 g/kg)and the low and high dose Ziyin Mingmu Pills groups(4.50,9.00 g/kg),in contrast to the C57BL/6 mice of the normal group,with 12 mice in each group.The mice had their retinal pathological changes detected by HE staining;their visual function detected by electroretinogram(ERG);their fundus conditions and retinal thickness detected by optical coherence tomography(OCT);their retinal blood perfusion detected by laser speckle blood flow technique;their mRNA expressions of Shh,Ptc,Smo,Gli1,N-myc and Cyclin mRNA detected by digital PCR;and their protein expressions of Shh,Ptc,Smo,Gli1,N-myc and Cyclin detected by immunofluorescence staining.RESULTS Compared with the normal group,the model group displayed pathological changes in the fundus and retina and decreased amplitudes of ERG a wave and b wave(P＜0.01);decreased retinal thickness(P＜0.01);decreased retinal blood perfusion(P＜0.01);and decreased retinal expressions of Shh,Ptc,Smo,Gli1,N-myc,Cyclin mRNA and protein(P＜0.01).Compared with the model group,the groups intervened with Ziyin Mingmu Pills or Leding shared improved pathological changes in the fundus and retina tissue,and increased retinal thickness(P＜0.01);increased retinal blood flow(P＜0.01);increased amplitudes of ERG a wave and b wave(P＜0.01);and increased retinal Shh,Ptc,Smo,Gli1,N-myc and Cyclin mRNA and protein expressions(P＜0.01).CONCLUSION Ziyin Mingmu Pills can improve the fundus pathological changes and visual function to delay RP in mice because of their efficacy in ameliorating retinal thickness and blood flow possibly by activating Shh signaling pathway.

[Objective] To explore the clinical application of cutaneous ureterostomy-flap embedding in radical cystectomy plus urinary diversion. [Methods] The clinical data of 10 patients with bladder cancer treated with this method in our hospital during Feb.and May 2023 were involved.Cutaneous ureterostomy-flap embedding was used in urinary diversion.The stoma-free rate and stenosis rate of stomas within 1 year postoperatively, differences in renal function indicators 1 day before operation and 1 year after operation, urinary diversion-related complications within 6 months postoperatively, including hydronephrosis, urinary tract infections, renal stones were analyzed. [Results] All surgeries were successfully completed.At 1 year postoperatively, renal function indicators showed no significant difference compared to preoperative levels (P>0.05). At 6 months postoperatively, 1 patient developed renal stones, successfully treated with surgery; 2 had urinary tract infection, recovered after antibiotic treatment; 2 had mild unilateral hydronephrosis, alleviated with conservative management.At 1 year postoperatively, the catheter-free rate was 80%(8/10), with no worsening of hydronephrosis or occurrence of ureteral obstruction, and the stent placement duration ranged from 97 to 211 days, average (151.63±42.47) days.The ureteral stent was not removed in 2 patients within 1 year, so the stoma stenosis rate was 20%(2/10). [Conclusion] The application of flap embedding in urinary diversion following radical cystectomy is a simple and safe procedure, with few postoperative complications, high success rate of stent removal, and overall favorable outcomes.

Objective:To explore the efficiency of radial collateral artery perforator flap to reconstruct defects of thumb web contracture release.Methods:The data of patients with moderate to severe thumb web contracture treated with radial collateral artery perforator flap from September 2018 to September 2022 in Department of Orthopedics-Hand Microsurgery of Xiangya Hospital, Central South University were analyzed retrospectively. A skin flap with the radial collateral artery perforating point as the center and the line connecting the deltoid muscle insertion point and the apex of the humeral lateral condyle as the axis were designed before surgery. During the operation, the skin scar in the thumb web area was first removed, and the contracted tissues such as deep fascia and muscles were loosened. Then, a skin flap was harvested along the design line and transferred to the recipient site. After vascular and nerve anastomosis under a microscope, the incision was intermittently sutured and a drainage tube was placed. The blood flow of the flap and complication were monitored closely. In the last follow-up, the distance and angle of thumb web were observed; the appearance, sensory recovery (excellent, good, moderate, and poor) and the hand function (S0 level to S4 level represented feeling no recovery to complete recovery) were evaluated.Results:A total of 8 patients were included, including 7 males and 1 female, aged 23-56 years (average of 40.3 years old). The distance of thumb web was 20-38 mm (average 26.9 mm), and the angle was 22°-36° (average 27.4°) before surgery. Five hands were classified as severe thumb web contracture, and 3 hands were moderate. The sizes of perforator flap were from 5.5 cm×3.5 cm-13.0 cm×6.5 cm. Seven flaps survived uneventfully and venous congestion occurred in 1 flap. After exploration, the flap survived completely. Primary healing of wounds occurred in the donor and recipient areas. Postoperative follow-up ranged from 6 months to 2.5 years (average 13.6 months). In the last follow-up, the distance of thumb web was 48-63 mm (average 57.1 mm), and the angle was 40°-52° (average 44.8°) post-operation. Thumb web function evaluation: excellent in 5 cases and good in 3 cases. All patients were satisfied with the thumb web. Sensory recovered to S3 in 3 cases, S2 in 4 cases and S1 in 1 case. The donor site healed well, leaving scars. There was no radial nerve damage, and elbow joint movement was normal.Conclusion:The radial collateral artery perforator flap has reliable blood supply, relatively simple operation and the appearance and function of thumb web restored well postoperatively. The application of radial collateral artery perforator flap is an effective procedure to repair the thumb web contracture.

Objective:To explore the efficiency of radial collateral artery perforator flap to reconstruct defects of thumb web contracture release.Methods:The data of patients with moderate to severe thumb web contracture treated with radial collateral artery perforator flap from September 2018 to September 2022 in Department of Orthopedics-Hand Microsurgery of Xiangya Hospital, Central South University were analyzed retrospectively. A skin flap with the radial collateral artery perforating point as the center and the line connecting the deltoid muscle insertion point and the apex of the humeral lateral condyle as the axis were designed before surgery. During the operation, the skin scar in the thumb web area was first removed, and the contracted tissues such as deep fascia and muscles were loosened. Then, a skin flap was harvested along the design line and transferred to the recipient site. After vascular and nerve anastomosis under a microscope, the incision was intermittently sutured and a drainage tube was placed. The blood flow of the flap and complication were monitored closely. In the last follow-up, the distance and angle of thumb web were observed; the appearance, sensory recovery (excellent, good, moderate, and poor) and the hand function (S0 level to S4 level represented feeling no recovery to complete recovery) were evaluated.Results:A total of 8 patients were included, including 7 males and 1 female, aged 23-56 years (average of 40.3 years old). The distance of thumb web was 20-38 mm (average 26.9 mm), and the angle was 22°-36° (average 27.4°) before surgery. Five hands were classified as severe thumb web contracture, and 3 hands were moderate. The sizes of perforator flap were from 5.5 cm×3.5 cm-13.0 cm×6.5 cm. Seven flaps survived uneventfully and venous congestion occurred in 1 flap. After exploration, the flap survived completely. Primary healing of wounds occurred in the donor and recipient areas. Postoperative follow-up ranged from 6 months to 2.5 years (average 13.6 months). In the last follow-up, the distance of thumb web was 48-63 mm (average 57.1 mm), and the angle was 40°-52° (average 44.8°) post-operation. Thumb web function evaluation: excellent in 5 cases and good in 3 cases. All patients were satisfied with the thumb web. Sensory recovered to S3 in 3 cases, S2 in 4 cases and S1 in 1 case. The donor site healed well, leaving scars. There was no radial nerve damage, and elbow joint movement was normal.Conclusion:The radial collateral artery perforator flap has reliable blood supply, relatively simple operation and the appearance and function of thumb web restored well postoperatively. The application of radial collateral artery perforator flap is an effective procedure to repair the thumb web contracture.