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 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.

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: This study systematically explore the efficacy and safety of fourth-generation chimeric antigen receptor T-cells (CAR-T), which express interleukin 7 (IL7) and chemokine C-C motif ligand 19 (CCL19) and target CD19, in relapsed or refractory large B-cell lymphoma. Methods: Our center applied autologous 7×19 CAR-T combined with tirelizumab to treat 11 patients with relapsed or refractory large B-cell lymphoma. The efficacy and adverse effects were explored. Results: All 11 enrolled patients completed autologous 7×19 CAR-T preparation and infusion. Nine patients completed the scheduled six sessions of tirolizumab treatment, one completed four sessions, and one completed one session. Furthermore, five cases (45.5%) achieved complete remission, and three cases (27.3%) achieved partial remission with an objective remission rate of 72.7%. Two cases were evaluated for disease progression, and one died two months after reinfusion because of uncontrollable disease. The median follow-up time was 31 (2-34) months, with a median overall survival not achieved and a median progression-free survival of 28 (1-34) months. Two patients with partial remission achieved complete remission at the 9th and 12th months of follow-up. Therefore, the best complete remission rate was 63.6%. Cytokine-release syndrome and immune effector cell-associated neurotoxicity syndrome were controllable, and no immune-related adverse reactions occurred. Conclusion: Autologous 7×19 CAR-T combined with tirelizumab for treating relapsed or refractory large B-cell lymphoma achieved good efficacy with controllable adverse reactions.
Humans ; Antibodies, Monoclonal/therapeutic use* ; Antigens, CD19 ; Chemokine CCL19 ; Immunotherapy, Adoptive ; Interleukin-7 ; Lymphoma, Large B-Cell, Diffuse/therapy* ; Programmed Cell Death 1 Receptor ; Receptors, Chimeric Antigen

Pericytes are essential components of vessel mural cells that function to regulate blood flow, clear or phagocytose debris, and are contractile cells enwrapping capillaries throughout the body. It controls vascular permeability and is involved in the development of blood vessels and is an important regulator and potential drug target of angiogenesis and vascular function. Pericytes are also thought to play a key role in the tumor microenvironment, especially during tumor growth and distal metastasis. Therefore,in this review we discuss the relationship between pericytes involved in tumor angiogenesis and tumor metastasis, as well as the use of targeted pericytes to treat tumors,with a view to providing a basis for subsequent studies.

COVID-19 has been prevalent for three years. The virulence of SARS-CoV-2 is weaken as it mutates continuously. However, elderly patients, especially those with underlying diseases, are still at high risk of developing severe infections. With the continuous study of the molecular structure and pathogenic mechanism of SARS-CoV-2, antiviral drugs for COVID-19 have been successively marketed, and these anti-SARS-CoV-2 drugs can effectively reduce the severe rate and mortality of elderly patients. This article reviews the mechanism, clinical medication regimens, drug interactions and adverse reactions of five small molecule antiviral drugs currently approved for marketing in China, so as to provide advice for the clinical rational use of anti-SARS-CoV-2 in the elderly.