Objective To develop and validate a prediction model to identify high-risk individuals who are at-risk to develop acute liver injury(ALI)within 180 days in new statin users,and to support early clinical intervention.Methods Data were sourced from the Yinzhou Regional Health Information Platform,covering statin initiators aged 18 years and older from January 1,2010,to October 31,2021.The dataset was divided into a derivation cohort and a temporal validation cohort based on the time of statin initiation.Predictors were selected using LASSO regression,and the model was constructed using the extreme gradient boosting(XGBoost)algorithm combined with cost-sensitive learning.Model performance was evaluated using Brier scores,Harrell's C-index,and calibration curves.Results A total of 126,440 statin initiators were included,with 90,542 in the derivation cohort and 35,898 in the validation cohort.Within 180 days of initial statin use,412(0.33％)patients developed ALI,including 305(0.34％)in the derivation cohort and 107(0.30％)in the validation cohort.The final model incorporated 16 predictors,which included demographic characteristics,lifestyle factors,family history,medical history,statin use,and concomitant medication use.The model demonstrated excellent overall performance[Brier score=0.0043,95％CI(0.0038,0.0049)],discrimination[Harrell's C-index=0.761,95％CI(0.725,0.794)],and calibration in internal validation.In temporal validation,the model also performed well[Brier score=0.0044,95％CI(0.0036,0.0052),Harrell's C-index=0.703,95％CI(0.614,0.781)].Conclusion This study develope and validate a prediction model for ALI in statin users,providing clinicians with a reliable tool for individualized risk assessment.This model can help achieve risk stratification and reduce the occurrence of ALI.

Objective To investigate the molecular mechanism by which STAT1 regulates the expression of APOL6 in order to mediate lipid deposition in tumor-associated macrophages(TAM)in laryngeal cancer tissues.Methods Real-time polymerase chain reaction,Western blotting,immunohistochemistry,and enzyme-linked immunosorbent assays were used to detect the expression levels of STAT1 and APOL6 in laryngeal cancer tissues,as well as the regulatory effect of STAT1 on APOL6 expression.Chromatin immunoprecipitation was used to elucidate the molecular mechanisms underlying APOL6 regulation by ST AT1.Oil Red O staining was used to evaluate the lipid deposition in TAM.Results The expression levels of STAT1 and APOL6 in laryngeal cancer tissues were significantly higher than those in the adjacent normal tissues(P＜0.01).STAT1 transcriptionally activated APOL6 gene expression.STAT1 overexpression sig-nificantly promoted the expression and secretion of APOL6 in laryngeal cancer cells and induced lipid deposition in TAM.Conclusion STAT1 is a novel transcription factor for the APOL6 gene.STAT1 promotes lipid deposition in the TAM of laryngeal cancer tissues by regu-lating APOL6 expression,thereby reshaping the lipid metabolism of TAM.

Objective To investigate the molecular mechanism by which STAT1 regulates the expression of APOL6 in order to mediate lipid deposition in tumor-associated macrophages(TAM)in laryngeal cancer tissues.Methods Real-time polymerase chain reaction,Western blotting,immunohistochemistry,and enzyme-linked immunosorbent assays were used to detect the expression levels of STAT1 and APOL6 in laryngeal cancer tissues,as well as the regulatory effect of STAT1 on APOL6 expression.Chromatin immunoprecipitation was used to elucidate the molecular mechanisms underlying APOL6 regulation by ST AT1.Oil Red O staining was used to evaluate the lipid deposition in TAM.Results The expression levels of STAT1 and APOL6 in laryngeal cancer tissues were significantly higher than those in the adjacent normal tissues(P＜0.01).STAT1 transcriptionally activated APOL6 gene expression.STAT1 overexpression sig-nificantly promoted the expression and secretion of APOL6 in laryngeal cancer cells and induced lipid deposition in TAM.Conclusion STAT1 is a novel transcription factor for the APOL6 gene.STAT1 promotes lipid deposition in the TAM of laryngeal cancer tissues by regu-lating APOL6 expression,thereby reshaping the lipid metabolism of TAM.

Objective This study aims to develop a guideline for assessing and maintaining intrinsic capacity in older adults,offer recommendations to professionals regarding these assessments,and encourage the implementation of evidence-based clinical practices across various settings,including communities,hospitals,nursing homes,and other geriatric care environments.Methods An evidence-based approach guided the collection of questions through a lit-erature review.Preliminary recommendations were developed through a systematic search of domestic and interna-tional guideline networks,professional association websites,and comprehensive databases.Subsequently,the recom-mendations were revised,and the consensus was achieved through a round of expert consensus meetings and 3 rounds of expert correspondence,culminating in the formation of the guidelines.Results The developed guideline encompasses 2 aspects and 5 dimensions of assessment and maintenance,comprising a total of 28 questions and 39 recommendations.Specifically,6 questions and 9 recommendations were formulated for the cognitive dimension,5 questions and 7 recommendations for the locomotion dimension,6 questions and 7 recommendations for the vitality dimension,6 questions and 9 recommendations for the psychological dimension,and 5 questions and 7 recommenda-tions for the sensory dimension.Among these,34 are classified as strong recommendations,while 5 are categorized as weak recommendations.Conclusion The guideline offers scientifically robust,acceptable,and comprehensible rec-ommendations that equip the professionals with a foundation for decision-making aiming at preserving the intrinsic capacity of older adults.

Objective This study aims to develop a guideline for assessing and maintaining intrinsic capacity in older adults,offer recommendations to professionals regarding these assessments,and encourage the implementation of evidence-based clinical practices across various settings,including communities,hospitals,nursing homes,and other geriatric care environments.Methods An evidence-based approach guided the collection of questions through a lit-erature review.Preliminary recommendations were developed through a systematic search of domestic and interna-tional guideline networks,professional association websites,and comprehensive databases.Subsequently,the recom-mendations were revised,and the consensus was achieved through a round of expert consensus meetings and 3 rounds of expert correspondence,culminating in the formation of the guidelines.Results The developed guideline encompasses 2 aspects and 5 dimensions of assessment and maintenance,comprising a total of 28 questions and 39 recommendations.Specifically,6 questions and 9 recommendations were formulated for the cognitive dimension,5 questions and 7 recommendations for the locomotion dimension,6 questions and 7 recommendations for the vitality dimension,6 questions and 9 recommendations for the psychological dimension,and 5 questions and 7 recommenda-tions for the sensory dimension.Among these,34 are classified as strong recommendations,while 5 are categorized as weak recommendations.Conclusion The guideline offers scientifically robust,acceptable,and comprehensible rec-ommendations that equip the professionals with a foundation for decision-making aiming at preserving the intrinsic capacity of older adults.

Objective To develop and validate a prediction model to identify high-risk individuals who are at-risk to develop acute liver injury(ALI)within 180 days in new statin users,and to support early clinical intervention.Methods Data were sourced from the Yinzhou Regional Health Information Platform,covering statin initiators aged 18 years and older from January 1,2010,to October 31,2021.The dataset was divided into a derivation cohort and a temporal validation cohort based on the time of statin initiation.Predictors were selected using LASSO regression,and the model was constructed using the extreme gradient boosting(XGBoost)algorithm combined with cost-sensitive learning.Model performance was evaluated using Brier scores,Harrell's C-index,and calibration curves.Results A total of 126,440 statin initiators were included,with 90,542 in the derivation cohort and 35,898 in the validation cohort.Within 180 days of initial statin use,412(0.33％)patients developed ALI,including 305(0.34％)in the derivation cohort and 107(0.30％)in the validation cohort.The final model incorporated 16 predictors,which included demographic characteristics,lifestyle factors,family history,medical history,statin use,and concomitant medication use.The model demonstrated excellent overall performance[Brier score=0.0043,95％CI(0.0038,0.0049)],discrimination[Harrell's C-index=0.761,95％CI(0.725,0.794)],and calibration in internal validation.In temporal validation,the model also performed well[Brier score=0.0044,95％CI(0.0036,0.0052),Harrell's C-index=0.703,95％CI(0.614,0.781)].Conclusion This study develope and validate a prediction model for ALI in statin users,providing clinicians with a reliable tool for individualized risk assessment.This model can help achieve risk stratification and reduce the occurrence of ALI.

Refractory ascites is one of the common complications of portal hypertension in decompensated liver cirrhosis and is characterized by extremely poor prognosis and high mortality rate. Transjugular intrahepatic portosystemic shunt (TIPS) is recommended by several international and national guidelines as one of the treatment methods after failure of large volume paracentesis combined protein infusion therapy. TIPS can effectively control the recurrence of ascites, but it can increase the risk of hepatic encephalopathy, and there are still controversies over whether it can prolong survival time. With a deeper understanding of TIPS, the maturity of surgical techniques, and the update of stent materials, it is urgent to reevaluate the position of TIPS in the treatment of refractory ascites due to portal hypertension. This article reviews the current status and advances in TIPS for the treatment of refractory ascites due to portal hypertension.

OBJECTIVE: The present study aimed to evaluate the therapeutic effect and explore the underlying mechanisms of Longxue Tongluo Capsule (LTC) on ischemic stroke rats. METHODS: Twenty-six rats were randomly divided into four groups, including sham group, sham + LTC group, MCAO group, and MCAO + LTC group. Ischemic stroke rats were simulated by middle cerebral artery occlusion (MCAO), and LTC treatment group were orally administrated with 300 mg/kg of LTC once daily for seven consecutive days. LTC therapy was validated in terms of neurobehavioral abnormality evaluation, cerebral infarct area, and histological assessments. The plasma metabolome comparisons amongst different groups were conducted by UHPLC-Q Exactive MS in combination with subsequent multivariate statistical analysis, aiming to finding the molecules in respond to the surgery or LTC treatment. RESULTS: Intragastric administration of LTC significantly decreased not only the neurobehavioral abnormality scores but also the cerebral infarct area of MCAO rats. The interstitial edema, atrophy, and pyknosis of glial and neuronal cells occurred in the infarcted area, core area, and marginal area of cerebral cortex were improved after LTC treatment. A total of 13 potential biomarkers were observed, and Youden index of 11 biomarkers such as LysoPC, SM, and PE were more than 0.7, which were involved in neuroprotective process. The correlation and pathway analysis showed that LTC was beneficial to ischemic stroke rats via regulating glycerophospholipid and sphingolipid metabolism, together with nicotinate and nicotinamide metabolism. Heatmap and ternary analysis indicated the synergistic effect of carbohydrates and lipids may be induced by flavonoid intake from LTC. CONCLUSION The present study could provide evidence that metabolomics, as systematic approach, revealed its capacity to evaluate the holistic efficacy of TCM, and investigate the molecular mechanism underlying the clinical treatment of LTC on ischemic stroke.

With the in-depth study of pathophysiology of acute respiratory distress syndrome(ARDS), the lung protective ventilation strategy of avoiding alveolar over-dilation and shear stress injury and maintaining alveolar opening has been recognized in the industry, in which low tidal volume ventilation is one of the important contents of ARDS lung protective ventilation strategy.This paper reviewed the effect of low tidal volume ventilation on the prognosis and clinical implementation of pediatric ARDS.

Objective:To investigate the efficacy of shunt after transjugular intrahepatic portosystemic shunt (TIPS) in liver cirrhosis accompanied with portal vein thrombosis (PVT).Methods:Forty-four cases with liver cirrhosis accompanied with PVT who underwent TIPS treatment from January 2015 to May 2018 were retrospectively analyzed. Clinical baseline data of the patients were collected. Portal vein pressure gradient (PVPG) before and after the surgery was recorded. Shunt patency was observed at 3, 6, 12, 18 and 24 months after the surgery. The influencing factors were determined by univariate and multivariate analysis.Results:Transjugular intrahepatic portosystemic shunt was successfully established in all 44 cases. The postoperative PVPG was lower than preoperative ( P < 0.01). The shunt patency rate after TIPS in PVT was 18.2% ( n = 8). The cumulative shunt patency rates at 3, 6, 12, 18, and 24 months after surgery were 95.5%, 90.7%, 90.7%, 86.8% and 74.4%, respectively. Univariate analysis showed that diabetes history, platelet level and prothrombin time-international normalized ratio were associated with postoperative shunt dysfunction. Multivariate analysis showed that diabetes history ( P = 0.007, OR = 28.606) was an independent risk factor for postoperative shunt dysfunction. Conclusion:TIPS is a safe and feasible procedure, which can effectively reduce the portal pressure in liver cirrhosis accompanied with PVT. Diabetic patients have a higher risk of postoperative shunt dysfunction. Therefore, clinical intervention should be strengthened for high-risk patients.