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.

Objective:To explore the formulation patterns and potential targets of traditional Chinese medicine (TCM) in the treatment of pneumoconiosis using data mining, network pharmacology, and Mendelian randomization (MR) .Methods:In November 2023, prescription data for TCM compound treatments of pneumoconiosis from the past five years were retrieved from the China National Knowledge Infrastructure (CNKI), Wanfang, and VIP databases. The formulation patterns of TCM for pneumoconiosis were analyzed based on drug frequency, association rules, and cluster analysis, followed by the identification of core drugs. Network pharmacology and MR analysis were then applied to determine the potential targets for pneumoconiosis treatment.Results:A total of 100 TCM prescriptions were included, involving 182 herbs, with 15 high-frequency herbs. A total of 24 strong association rules were identified, including 16 herbs. Cluster analysis identified three groups of drug combinations. The core drug combination, "Astragalus Root-Codonopsis Root-Tangkuei-Chinese Magnolia Vine Fruit-Danshen Root-Prepared Rehmannia Root" was determined, which interacted with 47 common targets associated with pneumoconiosis. Further protein-protein interaction (PPI) analysis identified 18 core targets, and MR analysis confirmed that Caspase-3 (CASP3) and Cathepsin B (CTSB) were risk factors for pneumoconiosis ( OR=1.35, 1.44; P=0.038, 0.038) . Conclusion:The core drug combination for the treatment of pneumoconiosis with TCM is "Astragalus Root-Codonopsis Root-Tangkuei-Chinese Magnolia Vine Fruit-Danshen Root-Prepared Rehmannia Root". The medication mainly focuses on tonifying lung qi, moistening dryness and stopping coughing, circulating blood and transforming stasis, which are supplemented with herbs for nourishing yin and moistening dryness, warming yang and dissipating cold. Finally, the key targets for treating pneumoconiosis are screened out, providing an important basis for the development of therapeutic drugs for it.

Objective:To investigate the protective effects of resveratrol (RSV) on human sperm cryopreservation and explore its underlying protective mechanisms.Methods:A total of 165 normal fresh semen samples were collected from the Reproductive Medicine Center, Department of Obstetrics and Gynecology and Human Sperm Bank of the First Affiliated Hospital of Anhui Medical University between December 2022 and December 2024. Among them, 65 samples were used to obtain semen parameters before and after conventional freezing. Each sample of the other 104 samples was mixed at a 2∶1 volume ratio with cryoprotectant containing 0, 10 -?, 10 -?, or 10 -? mol/L RSV, followed by cryopreservation in liquid nitrogen for 24 h. Post-thaw assessments included routine sperm parameters, sperm DNA fragmentation index (DFI) evaluated by sperm chromatin dispersion assay, reactive oxygen species (ROS) levels measured via flow cytometry, RSV and nuclear factor erythroid 2-related factor 2 (NRF2) interactions examined by molecular docking and cellular thermal shift assay (CETSA), NRF2 protein contents analyzed by immunofluorescence and Western blotting, mRNA levels of NRF2 and downstream antioxidant proteins Heme Oxygenase-1 (HO-1) and NAD(P)H: quinone oxidoreductase 1 (NQO1) quantified by qRT-PCR and effects of NRF2 inhibitor ML385 on sperm parameters. Results:Compared with fresh samples, conventional cryopreservation significantly reduced sperm motility (all P<0.001). The addition of 10 -? mol/L RSV significantly improved the percentage of forward motile sperm after freezing (26.98%±8.98% vs. 19.61%±8.03%, P<0.001) while reducing DFI (9.84%±3.81% vs. 15.06%±4.22%, P<0.001) and ROS levels ( P<0.001) compared with the post-freezing group without the addition of RSV. Both molecular docking analysis and CETSA confirmed that RSV interacted with NRF2. Notably, sperm cryopreserved with 10 -? mol/L RSV exhibited significantly higher contents of NRF2 and its downstream effectors HO-1 and NQO1 compared with the post-freezing group without the addition of RSV (all P<0.001). This protective effect was markedly attenuated by co-treatment with the NRF2 inhibitor ML385, as evidenced by a significant decline in sperm motility ( P<0.001). Conclusion:RSV exerts cryoprotective effects likely through NRF2-mediated antioxidant pathways, reducing oxidative stress and enhancing post-thaw sperm quality.

Objective:To investigate the protective effects of resveratrol (RSV) on human sperm cryopreservation and explore its underlying protective mechanisms.Methods:A total of 165 normal fresh semen samples were collected from the Reproductive Medicine Center, Department of Obstetrics and Gynecology and Human Sperm Bank of the First Affiliated Hospital of Anhui Medical University between December 2022 and December 2024. Among them, 65 samples were used to obtain semen parameters before and after conventional freezing. Each sample of the other 104 samples was mixed at a 2∶1 volume ratio with cryoprotectant containing 0, 10 -?, 10 -?, or 10 -? mol/L RSV, followed by cryopreservation in liquid nitrogen for 24 h. Post-thaw assessments included routine sperm parameters, sperm DNA fragmentation index (DFI) evaluated by sperm chromatin dispersion assay, reactive oxygen species (ROS) levels measured via flow cytometry, RSV and nuclear factor erythroid 2-related factor 2 (NRF2) interactions examined by molecular docking and cellular thermal shift assay (CETSA), NRF2 protein contents analyzed by immunofluorescence and Western blotting, mRNA levels of NRF2 and downstream antioxidant proteins Heme Oxygenase-1 (HO-1) and NAD(P)H: quinone oxidoreductase 1 (NQO1) quantified by qRT-PCR and effects of NRF2 inhibitor ML385 on sperm parameters. Results:Compared with fresh samples, conventional cryopreservation significantly reduced sperm motility (all P<0.001). The addition of 10 -? mol/L RSV significantly improved the percentage of forward motile sperm after freezing (26.98%±8.98% vs. 19.61%±8.03%, P<0.001) while reducing DFI (9.84%±3.81% vs. 15.06%±4.22%, P<0.001) and ROS levels ( P<0.001) compared with the post-freezing group without the addition of RSV. Both molecular docking analysis and CETSA confirmed that RSV interacted with NRF2. Notably, sperm cryopreserved with 10 -? mol/L RSV exhibited significantly higher contents of NRF2 and its downstream effectors HO-1 and NQO1 compared with the post-freezing group without the addition of RSV (all P<0.001). This protective effect was markedly attenuated by co-treatment with the NRF2 inhibitor ML385, as evidenced by a significant decline in sperm motility ( P<0.001). Conclusion:RSV exerts cryoprotective effects likely through NRF2-mediated antioxidant pathways, reducing oxidative stress and enhancing post-thaw sperm quality.

Objective:To explore the formulation patterns and potential targets of traditional Chinese medicine (TCM) in the treatment of pneumoconiosis using data mining, network pharmacology, and Mendelian randomization (MR) .Methods:In November 2023, prescription data for TCM compound treatments of pneumoconiosis from the past five years were retrieved from the China National Knowledge Infrastructure (CNKI), Wanfang, and VIP databases. The formulation patterns of TCM for pneumoconiosis were analyzed based on drug frequency, association rules, and cluster analysis, followed by the identification of core drugs. Network pharmacology and MR analysis were then applied to determine the potential targets for pneumoconiosis treatment.Results:A total of 100 TCM prescriptions were included, involving 182 herbs, with 15 high-frequency herbs. A total of 24 strong association rules were identified, including 16 herbs. Cluster analysis identified three groups of drug combinations. The core drug combination, "Astragalus Root-Codonopsis Root-Tangkuei-Chinese Magnolia Vine Fruit-Danshen Root-Prepared Rehmannia Root" was determined, which interacted with 47 common targets associated with pneumoconiosis. Further protein-protein interaction (PPI) analysis identified 18 core targets, and MR analysis confirmed that Caspase-3 (CASP3) and Cathepsin B (CTSB) were risk factors for pneumoconiosis ( OR=1.35, 1.44; P=0.038, 0.038) . Conclusion:The core drug combination for the treatment of pneumoconiosis with TCM is "Astragalus Root-Codonopsis Root-Tangkuei-Chinese Magnolia Vine Fruit-Danshen Root-Prepared Rehmannia Root". The medication mainly focuses on tonifying lung qi, moistening dryness and stopping coughing, circulating blood and transforming stasis, which are supplemented with herbs for nourishing yin and moistening dryness, warming yang and dissipating cold. Finally, the key targets for treating pneumoconiosis are screened out, providing an important basis for the development of therapeutic drugs for it.

AIM:To explore the therapeutic effect of teprenone(geranylgeranylacetone,GGA)on lipopolysac-charide(LPS)-induced cardiac dysfunction and its mechanism.METHODS:(1)Eight-week-old male C57BL/6 wild-type mice and carboxyl terminus of heat shock protein 70(HSP70)-interacting protein(CHIP)gene knockout mice were randomly divided into control group,LPS group,LPS+GGA group and GGA group,with 8 mice in each group.The model was established by intraperitoneal injection of LPS(25 mg/kg),and 1 h after LPS stimulation,mice were given intraperito-neal injection of GGA(100 mg/kg).The technique of high-resolution ultrasonography system was used to evaluate the car-diac function of mice.The serum of mice from each group were collected to detect the levels of creatine kinase-MB(CK-MB)and lactate dehydrogenase(LDH).HE staining was performed to observe histological changes of cardiac tissues.ELISA was used to detect the levels of tumor necrosis factor-α(TNF-α)and interleukin-6(IL-6)in cardiac tissues.West-ern blot was used to detect the protein levels of HSP70,CHIP,karyopherin-α 2(KPNA2),myeloperoxidase(MPO),vas-cular cell adhesion molecule(VCAM),intercellular cell adhesion molecule(ICAM),and nuclear factor-κB(NF-κB)in cardiac tissues.(2)In vitro cell inflammation model was established using mouse myocardial cells HL-1 stimulated with LPS.ELISA was used to detect the levels of TNF-α and IL-6 in cell supernatants.Western blot was used to detect the pro-tein expression levels of HSP70,CHIP,and KPNA2 in myocardial cells.Immunofluorescence staining was performed to observe the content of nuclear NF-κB.RESULTS:(1)GGA effectively improved cardiac function of LPS-stimulated mice,significantly increased ejection fraction and left ventricular fractional shortening(P<0.01),reduced serum levels of CK-MB and LDH(P<0.01),and alleviated myocardial injury.(2)GGA significantly reduced the release of TNF-α and IL-6 caused by LPS(P<0.01),as well as nuclear translocation of NF-κB,decreased the levels of KPNA2,MPO,VCAM and ICAM in cardiac tissues,and increased the levels of HSP70 in cardiac tissues and cells(P<0.01).(3)In CHIP knockout myocardial cells and mice,GGA failed to inhibit LPS-induced inflammatory response and lost its effect on im-proving cardiac function.CONCLUSION:The protective effect of GGA against LPS-caused cardiac dysfunction of mice is related to increasing expression of HSP70 and promoting CHIP activation,which inhibits the translocation of NF-κB into nucleus and suppresses inflammatory factor release.CHIP knockout abolishes the effects of GGA on reducing LPS-induced inflammatory response and myocardial injury.

Objective:To explore the current status of surgery for portal hypertension to grasp current status and future development of surgery in China.Methods:This study is jointly sponsored by China Hepatobiliary & Pancreatic Specialist Alliance & Portal Hypertension Alliance in China (CHESS).Comprehensive surveying is conducted for basic domestic situations of surgery for portal hypertension, including case load, surgical approaches, management of postoperative complications, primary effects, existing confusion and obstacles, liver transplantation(LT), laparoscopic procedures and transjugular intrahepatic portosystemic shunt(TIPS), etc.Results:A total of 8 512 cases of portal hypertension surgery are performed at 378 hospitals nationwide in 2021.Splenectomy plus devascularization predominated(53.0%)and laparoscopy accounted for 76.1%.Primary goal is preventing rebleeding(67.0%) and 72.8% of hospitals used preventive anticoagulants after conventional surgery.And 80.7% of teams believe that the formation of postoperative portal vein thrombosis is a surgical dilemma and 65.3% of hospitals practiced both laparoscopy and TIPS.The major reasons for patients with portal hypertension not receiving LT are due to a lack of qualifications for LT(69.3%)and economic factors(69.0%).Conclusions:Surgery is an integral part of management of portal hypertension in China.However, it is imperative to further standardize the grasp of surgical indications, the handling of surgical operation and the management of postoperative complications.Moreover, prospective, multi-center randomized controlled clinical studies should be performed.

Objective:To evaluate the impacts of tissue heterogeneity on dose calculation of cervical brachytherapy by comparing the doses calculated by two clinically used dose calculation method and the CT image-based Monte Carlo (MC) method.Methods:This study retrospectively selected 11 patients with cervical cancer treated with 3D brachytherapy in Anhui Provincial Cancer Hospital from January 2018 to June 2020. The dose distribution of each plan was calculated via three methods, dose calculation method described in American Association of Physicist in Medicine(AAPM) Task Group No. 43 Report (TG43-BT), Acuros BV(BV-BT) used to perform accurate dose calculations in high-dose-rate (HDR) brachytherapy with phantom heterogeneity, and CT image-based EGSnrc tool kit used to perform Monte Carlosimulation (MC-BT). The dose volumes( V3 Gy, V6 Gy, V9 Gy, and V12 Gy), target volume doses( D98, D90, D50), D2 cm 3 of organs at risk (OARs) calculated by the three methods were compared. Results:The HRCTV D90obtained by TG43-BT was 6.274 Gy, which was even overestimated by around 5% compared to the result calculated by MC-BT. Meanwhile, TG43-BT overestimated the dose volumesand the target volume doses compared to MC-BT.Except for D50 and V12 Gy, the differences between the doses to tumor calculated by BV-BT and MC-BT were not statistically significant( P>0.05). There was also no significant statistical difference between the D2 cm 3 of rectum, small intestine, and sigmoid calculated by BV-BT and MC-BT ( P>0.05). In contrast, the dose to D2 cm 3 of bladder determined by MC-BT was 4.609 Gy, which was notably higher than those deter mined by TG43-BT and BV-BT. Conclusions:TG43-BT overestimated the doses to tumor targets and most OARs since the effects of tissue heterogeneity were not taken into consideration. BV-BT performed efficient calculation and most of the dose distributionin target volume and OARs obtained by BV-BT were consistent with that calculated by MC-BT. Nevertheless, low accuracy occurred for the regions near the sources and full bladder, which warrants further caution in clinical evaluation.