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.

ObjectiveTo explore the sequential effects of hypoxic exercising on miR-27/PPARγ and lipid metabolism target gene and protein expression levels in the obesity rats’ liver. Methods13-week-old male diet-induced obesity rats were randomly divided into three groups (n＝10): normal oxygen concentration quiet group (N), hypoxia quiet group (H), hypoxic exercise group (HE). Exercise training on the horizontal animal treadmill for 1 h/d, 5 d/week for a total of 4 week, and the intensity of horizontal treadmill training was 20 m/min (hypoxic concentration was 13.6%). Comparison of the weights of perirenal fat and epididymal fat in rats across different groups and calculation of Lee’s index based on body weight and body length of rats in each group were done. And the serum concentrations of total cholesterol (TC), triglyceride (TG), low density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C) levels were detected. RT-PCR and Western Blot were used to detect the levels of miR-27, PPARγ, CYP7A1 and CD36. ResultsHypoxic exercise decreased the expression levels of miR-27 in the obese rats’ liver, however, the expression level of PPARγ was gradually increased. The expression levels of miR-27 in HE group were significantly lower than N group (P<0.05). The expression levels of PPARγ mRNA in N group were significantly lower than H group (P<0.05), especially lower than HE group (P<0.01). The protein expression of PPARγ protein in N group was significantly lower than that other groups (P<0.01). The expression of lipid metabolism-related genes and proteins increased in the obese rats’ liver. The expression of CYP7A1 mRNA in N group was significantly lower than H group (P<0.05), especially lower than HE group (P<0.01). The expression of CYP7A1 protein in the obese rats’ liver in N group was extremely lower than H group and HE group (P<0.01). The protein expression of CD36 in N group was significantly lower than that in HE group (P<0.05). Hypoxia exercise improved the related physiological and biochemical indexes of lipid metabolism disorder. The perirenal fat weight of obese rats in HE group was extremely lower than N group and H group (P<0.01), and the perirenal fat weight in N group was significantly higher than H group (P<0.05). The epididymal fat weight in N group was significantly higher than H group (P<0.05), and extremely higher than HE group (P<0.01). The Lee’s index in HE group was extremely lower than N group and H group (P<0.01). The serum concentration of TC in obese rats in HE group was extremely lower than N group and H group (P<0.01). The serum concentration of TG in HE group was extremely lower than N group and H group (P<0.01). The serum concentration of LDL-C in N group was extremely higher than HE group (P<0.01). The serum concentration of HDL-C in N group was extremely lower than H group (P<0.01). ConclusionHypoxia and hypoxia exercise may negatively regulate the levels of PPARγ by inhibiting miR-27 in the obese rats’ liver, thereby affecting the expression of downstream target genes CYP7A1 and CD36, and promoting cholesterol, fatty acid oxidation and HDL-C transport in the liver, and ultimately the lipid levels in obese rats were improved. The effect of hypoxia exercise on improving blood lipid is better than simple hypoxia intervention.

Debates persist regarding the efficacy and safety of azvudine, particularly its real-world outcomes. This study involved patients aged ≥60 years who were admitted to 25 hospitals in mainland China with confirmed SARS-CoV-2 infection between December 1, 2022, and February 28, 2023. Efficacy outcomes were all-cause mortality during hospitalization, the proportion of patients discharged with recovery, time to nucleic acid-negative conversion (T _NANC), time to symptom improvement (T _SI), and time of hospital stay (T _HS). Safety was also assessed. Among the 5884 participants identified, 1999 received azvudine, and 1999 matched controls were included after exclusion and propensity score matching. Azvudine recipients exhibited lower all-cause mortality compared with controls in the overall population (13.3% vs. 17.1%, RR, 0.78; 95% CI, 0.67-0.90; P = 0.001) and in the severe subgroup (25.7% vs. 33.7%; RR, 0.76; 95% CI, 0.66-0.88; P < 0.001). A higher proportion of patients discharged with recovery, and a shorter T _NANC were associated with azvudine recipients, especially in the severe subgroup. The incidence of adverse events in azvudine recipients was comparable to that in the control group (2.3% vs. 1.7%, P = 0.170). In conclusion, azvudine showed efficacy and safety in older patients hospitalized with COVID-19 during the SARS-CoV-2 omicron wave in China.

Objective To investigate the spatio-temporal expression of nuclear receptor subfamily 0 group B member 1(NR0B1)in synovial tissues of rheumatoid arthritis(RA),and to uncover the potential upstream signalling pathway that may regulate NR0B1 expression in human fibroblast-like synovial cells,thereby clarifying the possible factors that induce the disorder of NR0B1 expression in RA.Methods Patients with 25 RA and 18 osteoarthritis(OA)who did not receive any immunotherapy were recruited to obtain the synovial tissues of knee joint,as well as their related clinical test information,and the expression characteristics of NR0B1 in synovial tissue were investigated using Real-time PCR,Western blotting,immunohistochemistry and double immunofluorescent staining.Meanwhile,Pearson Chi-square test was used to evaluate the correlation between NR0B1 mRNA expression level and clinical parameters in RA patients.Furthermore,the MH7ANR0B1-/-cells that were stably knocked down of endogenous NR0B1 were generated,and the effects of NR0B1 deficiency on the phenotype of rheumatoid synovial cells enhanced by vascular endothelial growth factor(VEGF)were then evaluated by means of cell viability and apoptosis assays,colony formation assay,wound healing assay,and cell invasion assay.Last,we studied the molecular mechanism underlying interleuikin 6(IL-6)-mediated regulation of NR0B1 expression at the transcriptional level by using the STAT3-specific inhibitor intervention,siRNA,and dual luciferase reporter gene detection.Results The expression level of NR0B1 mRNA in the RA synovial tissues was significantly higher than that in synovial tissues from OA patients(P＜0.05).This trend of the increased NR0B1 mRNA expression correlated to clinical parameters,including C-reactive protein(CRP),rheumatoid factor(RF)and erythrocyte sedimentation rate(ESR),in RA patients.NR0B1 protein was predominantly immunolocalized in fibroblast-like synoviocytes of RA synovial tissues.Functionally,knockdown of NR0B1 expression markedly neutralize the VEGF-mediated enhancement of cell viability,resistance to apoptosis,clonogenicity,as well as migration and invasion in the MH7A cells.Additionally,IL-6 could specifically regulate NR0B1 expression in the MH7A synovial cells.IL-6 upregulated the transcriptional expression of NR0B1 mainly through induction of the phosphorylation of its downstream STAT3 at the Tyr-705 site.Conclusion The upregulated NR0B1 expression in fibroblast-like synoviocytes is positively correlated with the progression of RA.The proinflammatory cytokine IL-6 potentiates the transactivation of NR0B1 by inducing the phosphorylation of Tyr-705 site of its downstream effector STAT3.NR0B1 may be a significant breakthrough point for understanding the interaction between IL-6 and VEGF signaling pathways and the progression of RA.

Traditional Chinese medicine is a treasure of Chinese civilization,which has undergone thousands of years of precipitati-on and clinical verification.According to the theory of traditional Chinese medicine,ancient doctors used natural medicines and natural means to promote self-regulation and damage repair of the body.In recent years,as an important tool to repair body damage,stem cells have set off a research upsurge.With the continuous deepening of stem cell research and the continuous expansion of the fields in-volved,the potential correlation between traditional Chinese medicine and stem cells has attracted more and more domestic and foreign researchers to invest in research.This paper expounds regenerative medicine and stem cells,the advantages of Chinese medicine in regulating stem cells,and the opportunities and challenges faced by Chinese medicine and regenerative medicine,and reviews the cur-rent research trends and frontier trends in this field,in order to provide useful references for subsequent studies.

Objective To analyze the clinical outcomes of extended thymectomy for myasthenia gravis (MG) patients under different surgical approaches, and to determine the factors affecting the prognosis of MG. Methods The MG patients who underwent extended thymectomy from January 2014 to March 2021 in our hospital were retrospectively collected. According to the surgical approach, they were divided into a subxiphoid group and an intercostal group, and the perioperative results and prognosis were compared between the two groups. A “good outcome” was defined as complete stable remission (CSR), pharmacological remission (PR) or minimal manifestations state (MMS); a “poor outcome” was defined as outcomes worse than MMS. Univariate and multivariate logistic regression analyses were performed to assess the factors associated with the good outcomes. Results A total of 187 MG patients were included in the study, including 82 males and 105 females, with a median age of 50 (36, 60) years. There were 134 patients in the intercostal group and 53 patients in the subxiphoid group. Compared with the intercostal group, although the operation time of the subxiphoid group was longer [200.0 (172.0, 232.0) min vs. 141.0 (118.0, 169.0) min, P<0.001], the intraoperative blood loss was less [10.0 (10.0, 20.0) mL vs. 20.0 (10.0, 50.0) mL, P<0.001], the postoperative hospital stay was shorter [3.0 (2.5, 4.0) d vs. 5.0 (3.0, 7.0) d, P<0.001], and the incidence of complications was lower [1 (1.9%) vs. 26 (19.4%), P=0.001]. A total of 159 (85.0%) patients were followed up for a median period of 46 (13, 99) months, with a good outcome rate of 90.6% and CSR rate of 33.3%. There were no statistical differences in PR, MMS or overall good outcome rates between the two groups (P>0.05). Multivariate logistic analysis showed that age≤50 years was an independent predictor for "good outcome" of MG patients. Conclusion Extended thymectomy via subxiphoid for MG is a safe, feasible and effective surgical approach.

Objective:To compare the clinical efficacy between bone transport technique combined with bone grafting plus internal fixation and simple bone transport technique in the treatment of large segmental bone defects at lower limbs after trauma.Methods:A retrospective study was conducted to analyze the clinical data of 42 patients with large segmental bone defects at lower limbs after trauma who had been treated at Department of Trauma Orthopaedics, Honghui Hospital Affiliated to Medicine College, Xi'an Jiaotong University from September 2015 to September 2019. The patients were divided into 2 groups according to the different methods of repairing bone defects. In group A of 18 patients subjected to bone transport combined with bone grafting plus internal fixation, there were 11 males and 7 females with an age of (35.2±10.3) years, and 12 tibial defects and 6 femoral defects; in group B of 24 patients subjected to simple bone transport, there were 15 males and 9 females with an age of (37.3±9.4) years, and 17 tibial defects and 7 femoral defects. The external fixation time (EFT), external fixation index (EFI), total cure time and complications were recorded and compared between the 2 groups. At the last follow-up, the Ennecking score for limb functional recovery (score/total score 30) and Self-rating Anxiety Scale (SAS) were used to evaluate respectively the functional recovery of the limbs and postoperative anxiety.Results:The 2 groups were comparable because there was no significant difference between them in preoperative general data or follow-up time ( P>0.05). There was no statistically significant difference in the number of surgeries between the 2 groups ( P>0.05). The EFT [(5.9±1.5) months], EFI [(0.45±0.09) months/cm], total treatment time [(16.2±2.4) months], Ennecking score for limb functional recovery (87.0%±8.6%), SAS score [(43.2±9.0) points], and complications per capita [(0.4±0.2) times/case] in group A were significantly better than those in group B [(15.3±4.2) months, (1.19±0.28) months/cm, (19.7±3.5) months, (77.3%±9.2%), (58.2±9.3) points, and (1.2±0.5) times/case] (all P<0.05). Conclusion:In the treatment of large segmental bone defects at lower limbs, compared with simple bone transport technique, bone transport technique combined with bone grafting plus internal fixation has advantages of shorter external fixation time and overall cure time, a lower rate of complications, and better functional recovery of the limbs.

Objective:To investigate acute adverse events and pregnancy outcome after vaccination of inactivated COVID-19 vaccine in the first trimester of pregnancy.Methods:The retrospective-prospective cohort study was conducted among pregnant women of 11-13 +6 weeks of gestation who visited the obstetric clinics for prenatal check in Lianyungang Maternal and Child Health Hospital from May to November in 2021, after registration for perinatal health cards in the community. Those who met the inclusion criteria were recruited and were divided into vaccination group and non-vaccination group according to whether they received inactivated COVID-19 vaccine in the first trimester. Women in the vaccination group were further divided into 1-dose group and 2-dose group. Information, including pregnancy-related screening, pregnancy complications, pregnancy outcome and acute adverse events, were collected and compared with independent samples t-test or ANOVA, Kruskal- Wallis H test or Mann-Whitney U test, χ2 test or Fisher's exact probability method. Results:Totally, 105 pregnant women were analyzed in 1-dose group, 90 in 2-dose group, and 194 in non-vaccination group. (1) There were no statistically significant differences in the occurrence of acute adverse events [1-dose group: 2.86% (3/105); 2-dose group: 6.67% (6/90); non-vaccination group: 4.63% (9/194); χ2=1.59; vaccination group was 4.61% (9/195), when compared with non-vaccination group, χ2=0.00], abnormal pregnancy-related screening indicators and abnormal pregnancy outcome among the three groups (all P>0.05), neither between the vaccination and non-vaccination group (all P>0.05). The acute adverse events in these women included fever, pain at the inoculation site, fatigue, local induration and rash.(2) The differences in hypertensive disorders in pregnancy among the three groups were statistically significant [1-dose group: 10.5%(11/105); 2-dose group: 17.8%(16/90); non-vaccination group: 7.7%(15/194); χ2=6.46, P=0.040], and the incidence was higher in the 2-dose group than that in the non-vaccination group (adjusted by Bonferroni, P<0.017). (3) Regarding other pregnancy complications, no difference was found among the three groups (all P>0.05), neither between the vaccination and non-vaccination group (all P>0.05). Conclusion:The risk of acute adverse events and adverse pregnancy outcome is similar in pregnant women who received inactivated COVID-19 vaccine versus those who did not in the first trimester, and regular blood pressure monitoring is recommended for those who received two doses of inactivated COVID-19 vaccine.