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.

Nuclear factor-kappa B （NF-κB） is an important intracellular transcription factor widely involved in the processes such as immune response， inflammatory response， cell proliferation， and apoptosis. The abnormal activation of the NF-κB signaling pathway plays a pivotal role in various liver diseases including chronic hepatitis， liver fibrosis， liver cirrhosis， and hepatocellular carcinoma. Extensive studies have shown that inhibiting NF-κB activity may effectively reduce inflammation and fibrosis and improve metabolic disorders. Several natural compounds， such as matrine and salvianolic acid B， have shown the potential in suppressing NF-κB activity， thereby exerting anti-inflammatory， anti-fibrotic， and anti-tumor effects. This article systematically reviews the critical role of the NF-κB signaling pathway in liver diseases and its potential as a therapeutic target， in order to highlight its potential as a therapeutic target for liver diseases and provide new directions for the treatment of liver diseases.

The ethics committee of organ transplantation technology and clinical application in a hospital has encountered some difficulties and typical cases in its review work and practice for many years. Sometimes, it is difficult to make a decision in these dilemmas. Based on the previous experience of the hospital in the ethical review of organ donation and transplantation, combined with two typical cases, this paper discussed and analyzed two review points of whether the voluntary unpaid donation and the principle of informed consent were met, and whether the risk-benefit ratio was reasonable, and put forward relevant ethical and legal countermeasure for further research by institutional ethics committees and other parties, in order to provide reference for discussing the practical problems and ethical confusion of ethical review of organ donation and transplantation.

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease affecting both upper and lower motor neurons. ALS patients develop progressive muscle atrophy, muscle weak and paralysis, finally died of respiratory failure. ALS is characterized by fast aggression and high mortality. What' s more, the disease is highly heterogeneous with unclear pathogenesis and lacks effective drugs for therapy. In this review, we summarize the main pathological mechanisms and the current drugs under development for ALS, which may provide a reference for the drug discovery in the future.

ObjectiveTo investigate the role and possible mechanism of action of rhubarb decoction （RD） retention enema in improving inflammatory damage of brain tissue in a rat model of mild hepatic encephalopathy （MHE）. MethodsA total of 60 male Sprague-Dawley rats were divided into blank group （CON group with 6 rats） and chronic liver cirrhosis modeling group with 54 rats using the complete randomization method. After 12 weeks， 40 rats with successful modeling which were confirmed to meet the requirements for MHE model by the Morris water maze test were randomly divided into model group （MOD group）， lactulose group （LT group）， low-dose RD group （RD1 group）， middle-dose RD group （RD2 group）， and high-dose RD group （RD3 group）， with 8 rats in each group. The rats in the CON group and the MOD group were given retention enema with 2 mL of normal saline once a day； the rats in the LT group were given retention enema with 2 mL of lactulose at a dose of 22.5% once a day； the rats in the RD1， RD2， and RD3 groups were given retention enema with 2 mL RD at a dose of 2.5， 5.0， and 7.5 g/kg， respectively， once a day. After 10 days of treatment， the Morris water maze test was performed to analyze the spatial learning and memory abilities of rats. The rats were analyzed from the following aspects： behavioral status； the serum levels of alanine aminotransferase （ALT）， aspartate aminotransferase （AST）， interleukin-1β （IL-1β）， interleukin-6 （IL-6）， and tumor necrosis factor-α （TNF-α） and the level of blood ammonia； pathological changes of liver tissue and brain tissue； the mRNA and protein expression levels of phosphatidylinositol 3-kinase （PI3K）， protein kinase B （AKT）， and mammalian target of rapamycin （mTOR） in brain tissue. A one-way analysis of variance was used for comparison of continuous data between multiple groups， and the least significant difference t-test was used for further comparison between two groups. ResultsCompared with the MOD group， the RD1， RD2， and RD3 groups had a significantly shorter escape latency （all P<0.01）， significant reductions in the levels of ALT， AST， IL-1β， IL-6， TNF-α， and blood ammonia （all P<0.05）， significant alleviation of the degeneration， necrosis， and inflammation of hepatocytes and brain cells， and significant reductions in the mRNA and protein expression levels of PI3K， AKT， and mTOR in brain tissue （all P<0.05）， and the RD3 group had a better treatment outcome than the RD1 and RD2 groups. ConclusionRetention enema with RD can improve cognitive function and inflammatory damage of brain tissue in MHE rats， possibly by regulating the PI3K/AKT/mTOR signaling pathway.

OBJECTIVE To mine the adverse drug events （ADE） signals for gilteritinib， and provide a reference for safe drug use in clinic. METHODS ADE reports with gilteritinib as the primary suspected drug were extracted from the FDA Adverse Event Reporting System （FAERS） database from February 1st， 2018 to December 31st， 2023. Reporting odds ratio （ROR） and proportional reporting ratio （PRR） were applied to detect the risk signals from the data in the FAERS database. The classification and statistics of collected signal data were conducted by using the preferred term （PT） and systemic organ class （SOC） in ADE terminology set of the Medical Dictionary for Regulatory Activities （24.1 edition）. RESULTS Totally， 2 755 gilteritinib-related ADE reports were collected from the database， involving 676 ADE signals （95 positive signals）， 313 PTs and 25 SOCs. Among them， nine signals were not recorded in the package insert. The top 5 PTs consisted of abnormal liver function， decreased platelet count， febrile neutropenia， pneumonia and myelosuppression. The top 6 SOCs for positive signal counts were examinations， general disorders and administration site conditions， respiratory， thoracic and mediastinal disorders， infections and infestations， heart organ disorders， and nervous system disorders. ADEs not recorded in the drug package insert included pneumonia， myelosuppression， decreased blood cell count， sepsis， hemorrhage， infection （not specifically referred to）， septic shock， respiratory failure， and aspergillosis. CONCLUSIONS In addition to paying attention to common ADEs such as liver dysfunction and thrombocytopenia， it is necessary to monitor ADEs with strong signals that are not mentioned in the drug instructions when using gefitinib， such as pneumonia， bone marrow suppression， cytopenia， sepsis， bleeding， infection （not specifically referred to）， septic shock， respiratory failure， Aspergillus infection， elevated serum creatinine and interstitial lung disease.

ObjectiveTo construct a macro-evaluation tool for dampness syndrome （DS） animal model， which will provide a basis for experimental research on dampness syndrome in traditional Chinese medicine （TCM）. MethodsConceptual framework of this study was clarified through discussions within the core working group， and dimensions of the evaluation of the animal model of DS were identified according to TCM principles. We searched CNKI， Wanfang， VIP and SinoMed databases from the inception to June 30th， 2023， on experiments involving dampness syndrome animals to create a pool of items about DS animal models. The core items were selected and extracted for factor analysis and cluster analysis. An expert importance rating questionnaire was developed based on the results of the literature review， analyzing the distribution of item scores， importance averages， and coefficient of variation. Through a comprehensive analysis of literature， expert importance scoring， and specific expert opinions， items that did not meet anyone of the criteria of average importance rating ≥2.04， coefficient of variation ≤30%， or literature eva-luation frequency ≥2% were removed， thereafter， the macro-evaluation tool for DS animal model was preliminarily constructed. ResultsSpirit and body state， autonomic activity state， body surface characteristics， diet， urination and defecation， tongue manifestation， and motor behavior assessment were constructed as the seven dimensions in the evaluation of DS animal model. A total of 348 papers about animal experiments were included and analyzed， resulting in a saturated pool of 72 items， which was refined to 38 core items of DS animal models. Factor analysis obtained 16 common factors， which were further clustered into two categories， named dampness transforming from heat syndrome and dampness transforming from cold syndrome. The expert importance scoring showed that the Kendall harmony coefficient was 0.359 （P＜0.05） indicating a high level of agreement， coordination and reliability among the experts. Notably， 50% or more of the experts considered the items thick and greasy tongue coating， unclean perianal area， loose stools， lethargy， unformed stools， and listless expression as very important. The median scores for all items were 2.04（1.73， 2.37）， with a coefficient of variation ranging from 19.73% to 53.38%. After expert evaluation， the macro-evaluation tool for DS animal model in TCM with 33 items and corresponding criteria for assessing the formation of DS models was finally contructed. ConclusionThe Macro-evaluation tool for DS animal model in TCM is highly scientific， credible， and operable， and can be utilized in DS animal experiments after its characteristics are actually evaluated.

Objective To explore the role of pulmonary surfactant(PS)combined with budesonide in improving oxygenation and clinical outcomes of neonatal acute respiratory distress syndrome(ARDS).Methods The present study is a historically controlled trial.Infants with ARDS requiring mechanical ventilation and PS replacement therapy were collected from the neonatal unit of Southwest Medical University.Those from January 2022 to November 2022 were set as intervention group(PS+ budesonid,n=35),treated with intratracheal instillation of a mixed suspension of budesonide(0.25 mg/kg)and PS(200 mg/kg),and continuous budesonide nebulization(0.25 mg/kg,twice per day)until withdrawal,then compared with a historical cohort,who just received intratracheal instillation of PS(200 mg/kg)(January 2020-December 2021,PS group,n=35).Baseline data such as gender,mode of delivery,1 min and 5 min Apgar score,birth weight,gestational age,time of onset,and cause of onset were recorded in both groups.The oxygenation and clinical outcomes of infants were compared between the two groups,including:(1)Arterial blood gas analysis indicators,such as partial pressure of oxygen(PaO2)and oxygenation index(OI)before treatment and at 6,12 and 24 hours of treatment;(2)Clinical observation and evaluation indicators,such as the time to withdrawal,duration of oxygen supplementation,length of stay,improvement of the radiological images of the lungs at 72 h of treatment,and repeated PS use;(3)Blood chemistry indicators,such as white blood cell(WBC),neutrocyte(NEU),procalcitonin(PCT)before treatment and at 3 and 7 days of treatment;and(4)Observation indicators of complications,weight growth,and mortality outcomes,such as the incidences of intracranial hemorrhage,gastrointestinal hemorrhage,neonatal necrotizing enterocolitis(NEC),and hyperglycemia,weight growth,and fatality rate.Results The differences in baseline data between the two groups were not statistically different(P＞0.05).The levels of PaO2 of the two groups were increased after treatment for different time periods,while the levels of OI were decreased(P＜0.001),and the levels of above indexes changed more significantly in PS+budesonide group than those in PS group(P＜0.05).The time to withdrawal,duration of oxygen supplementation,and length of stay in PS+budesonide group were shorter than those in PS group;the radiological images of the lungs showed that the pulmonary inflammation absorption was significantly better in PS+ budesonide group than that in PS group,while no significant difference between the two groups of infants with repeated PS use.The NEU was significantly higher in PS+budesonide group than in PS group at 3 d and 7 d of treatment(P＜0.001);and at 3 days of treatment,the PCT levels were significantly lower in PS+budesonide group than that in PS group(P＜0.05).The incidences of intracranial hemorrhage,gastrointestinal hemorrhage,NEC,hyperglycemia,weight growth,and fatality rate were not significantly different between the two groups(P＞0.05).Conclusion The use of budesonide in addition to surfactant may improve the oxygenation of neonates with ARDS,improve the inflammatory infiltrates in lungs,shorten the duration of mechanical ventilation and oxygen supplementation,and without short-term complications associated with budesonide use.