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.

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Objectives:To explore the spatial distribution characteristics, trend changes, and spatial clustering of esophageal cancer among residents in China at the county (city, district) scale, a spatial epidemiological approach was used, with the aim of providing localized evidence for the prevention and treatment of esophageal cancer in China.Methods:The data source was the incidence (crude rate) and mortality (crude rate) of esophageal cancer from 2005 to 2016 in the 2008-2019 edition of China Cancer Registration Annual Report published by the National Cancer Center. The Joinpoint model was used for time trend analysis. The tumor registration area in 2016 was selected as the study area for spatial feature analysis, with a total of 487 counties (cities and districts), covering 27.6% of the national population. Spatial autocorrelation analysis was performed to reveal spatial distribution characteristics by using Arcgis 10.6 software, and spatial scanning statistics was used to analyze spatial clustering characteristics by using SaTScan 9.5 software. The log-likelihood ratio ( LLR) and relative risk ( RR) were calculated in different windows, and the region with the largest LLR value represented the most likely cluster. Results:From 2005 to 2016, the incidence and mortality rate of esophageal cancer in China showed a trend of increasing at first and then decreasing. The incidence and mortality rate of esophageal cancer in 2016 were characterized by spatial positive correlation. High incidence and high mortality were mainly concentrated in the areas through which the Huaihe River flowed. The primary clusters (taking high incidence rate as an example LLR=6 374.41, RR=2.37, P＜0.001) were mainly distributed in Jiangsu, Anhui and Shandong in eastern China and eastern Henan and southern Hebei in central China, and secondary clusters (taking high incidence rate as an example LLR=1 971.19, RR=1.91, P＜0.001) in Gansu, Ningxia Hui Autonomous Region, Shaanxi, Sichuan and other central and western regions. Conclusions:The incidence and mortality of esophageal cancer in China have decreased since 2010. The disease burden of esophageal cancer has obvious spatial differences, and measures should be taken according to local conditions in high-risk cluster areas such as the Huaihe River basin.

Objectives:To explore the spatial distribution characteristics, trend changes, and spatial clustering of esophageal cancer among residents in China at the county (city, district) scale, a spatial epidemiological approach was used, with the aim of providing localized evidence for the prevention and treatment of esophageal cancer in China.Methods:The data source was the incidence (crude rate) and mortality (crude rate) of esophageal cancer from 2005 to 2016 in the 2008-2019 edition of China Cancer Registration Annual Report published by the National Cancer Center. The Joinpoint model was used for time trend analysis. The tumor registration area in 2016 was selected as the study area for spatial feature analysis, with a total of 487 counties (cities and districts), covering 27.6% of the national population. Spatial autocorrelation analysis was performed to reveal spatial distribution characteristics by using Arcgis 10.6 software, and spatial scanning statistics was used to analyze spatial clustering characteristics by using SaTScan 9.5 software. The log-likelihood ratio ( LLR) and relative risk ( RR) were calculated in different windows, and the region with the largest LLR value represented the most likely cluster. Results:From 2005 to 2016, the incidence and mortality rate of esophageal cancer in China showed a trend of increasing at first and then decreasing. The incidence and mortality rate of esophageal cancer in 2016 were characterized by spatial positive correlation. High incidence and high mortality were mainly concentrated in the areas through which the Huaihe River flowed. The primary clusters (taking high incidence rate as an example LLR=6 374.41, RR=2.37, P＜0.001) were mainly distributed in Jiangsu, Anhui and Shandong in eastern China and eastern Henan and southern Hebei in central China, and secondary clusters (taking high incidence rate as an example LLR=1 971.19, RR=1.91, P＜0.001) in Gansu, Ningxia Hui Autonomous Region, Shaanxi, Sichuan and other central and western regions. Conclusions:The incidence and mortality of esophageal cancer in China have decreased since 2010. The disease burden of esophageal cancer has obvious spatial differences, and measures should be taken according to local conditions in high-risk cluster areas such as the Huaihe River basin.

Accurate determination of the thickness of multi-layered nanofilm materials is of great importance to advance the development of thin film deposition technology and ensure the quality assurance of photovoltaic materials.Laser ablation inductively coupled plasma mass spectrometry(LA-ICP-MS)has been successfully employed for depth profiling of thin film materials,such as metal coatings.However,the accuracy of interface discrimination and thin layer thickness measurement is limited by the mixing effects of elemental signals.In this work,a high-depth resolution method for measuring the thin film thickness of lead sulfide(PbS)colloidal quantum dot(CQD)photovoltaic devices by LA-ICP-MS was introduced.The influence of different laser parameters on the mixing effects of element signals during the ablation process was compared,and the results showed that the laser ablation behavior of multi-layered nanofilm materials were improved and the mixing of element signals were reduced by optimizing parameters such as laser energy density and spot diameter.Meanwhile,a self-developed aerosol rapid wash-out small volume tubular ablation cell was used to effectively improve the aerosol transport efficiency,and the wash-out time of aerosol was(1.60±0.6)s.Compared with commercial cylindrical ablation cells,the depth profile of multi-layer thin film samples was clearer.The depth profile of the interlayer interface showed a significant melting phenomenon during the ablation of the PbS CQD layer,leading to severe mixing of elemental signals at the PbS/ZnO layer interface.Under the conditions such as 2.5 J/cm2 laser energy,32 μm spot diameter,and 1 Hz repetition rate,the average ablation rates of Au,PbS and ZnO layers in PbS CQD photovoltaic devices were(60±2)nm/pulse,(69±5)nm/pulse,and(22±2)nm/pulse,with depth resolution of(26±2)nm,(213±11)nm,and(68±6)nm,respectively.The thickness of PbS CQD photovoltaic device films from the same batch was determined,and the test results exhibited good consistency with scanning electron microscope(SEM)measurement values,with a relative deviation of less than 6％.This method could accurately determine the thickness of nanoscale multilayer thin film samples,which was crucial for improving the performance of photovoltaic devices and controlling product quality.

Background and aim:Few studies have reported hepatitis B surface antigen(HBsAg)kinetics after nucleos(t)ide analog(NA)discontinuation in patients with noncirrhotic chronic hepatitis B(CHB).The study specifically investigated long-term HBsAg kinetics after NA discontinuation. Methods:Between January 2014 to January 2024,this study prospectively enrolled 106 outpatients with noncirrhotic CHB who met the discontinuation criteria after NA consolidation treatment.Demographic,clinical,and laboratory data were collected and analyzed after NA discontinuation. Results:Ninety-six patients who finished 5 years of follow-up were included.HBsAg remained unde-tectable in 29 patients with end of treatment(EOT)HBsAg negativity.Among 67 patients with EOT HBsAg positivity,HBsAg seroclearance occurred in 12(17.9％)patients with an estimated annual inci-dence of HBsAg seroclearance of 3.6％.Patients with EOT HBsAg levels of ≤1000 IU/mL had a higher HBsAg seroclearance rate than those with EOT HBsAg levels of＞1000 IU/mL(33.3％vs.5.4％).The pro-portion of patients with HBsAg ≤1000 IU/mL increased during follow-up.Logistic regression analysis indicated that the EOT HBsAg level was an independent factor for HBsAg seroclearance and an HBsAg level decline exceeding 1 log10 IU/mL.The optimal EOT HBsAg cutoff for both HBsAg seroclearance and an HBsAg level decline exceeding 1 log10 IU/mL was 359 IU/mL. Conclusions:Patients with EOT HBsAg negativity experienced no relapse and maintained HBsAg sero-clearance during 5 years of follow-up after NA discontinuation.A higher HBsAg seroclearance rate can be obtained in patients with EOT HBsAg levels of ≤1000 IU/mL during 5 years of follow-up after NA discontinuation.Close monitoring and proper NA retreatment are recommended to guarantee the safety of NA discontinuation.

Objective To mine the adverse drug events(ADE)signal of avatrombopag,an effective drug for thrombocytopenia treatment,based on real world data in order to provide reference for its clinical safety application.Methods The OpenVigil2.1 pharmacovigilance platform was used to obtain the ADE report data of avatrombopag from May 2018 to March 2023 in the database of FDA adverse event reporting system(FAERS).The ADE signals were classified and described by the system organ class(SOC)and preferred term(PT)of the ADE terminology set in the Medical Dictionary for Regulatory Activities(MedDRA),and reporting odds ratio(ROR)and UK Medicines and Healthcare Products Regulatory Agency(MHRA)comprehensive standard were used to detect the positive ADE signals.Results A total of 1 879 ADE reports related to avatrombopag were obtained,24 SOCs were involved,and 28 positive ADE signals were detected at PT level.Among these signals,the strongest ones were renal vein thrombosis,portal vein thrombosis and graft versus host disease,while the reports accounting for the largest numbers were headache,fatigue and asthenia.There were 8 ADE signals discovered newly,that is,seasonal allergy,back disorder,musculoskeletal discomfort,flatulence,hypersomnia,rash macular,emotional disorder,and rhinorrhoea.Conclusion For clinical use of avatrombopag,clinicians should not only concern the risk of thrombosis,but also pay close attention to ADE signals such as seasonal allergy,back disorder,musculoskeletal discomfort,flatulence,hypersomnia,rash macular,emotional disorder,and rhinorrhoea that are not documented in the instructions.

OBJECTIVE To provide reference for the clinically safe application of acalabrutinib by mining and analyzing the risk signals of adverse drug events （ADE）. METHODS The acalabrutinib-induced ADE reports were extracted from the U.S. FDA adverse event reporting system using the OpenVigil 2.1 platform from November 1， 2017 to March 31， 2023. The reporting odds ratio （ROR） method and composite criteria method from the Medicines and Healthcare Products Regulatory Agency （MHRA） were used for detection of ADE signals. RESULTS There were 7 869 ADE reports of acalabrutinib as the primary suspect drug and 142 ADE positive signals were detected from them， involving 20 system organ classes， which was generally consistent with the ADE recorded in the drug instruction of acalabrutinib， mainly involving general disorders and administration site conditions， various inspection， blood and lymphatic system disorders， various neurological disorders and cardiac disorders. In addition， this study identified several new potential ADE signals that were not mentioned in the drug instruction， including sudden cardiac death， pulmonary toxicity， tumor lysis syndrome， pleural effusion， dyspepsia， gastroesophageal reflux disease， bone pain， decreased blood pressure， and abnormal blood sodium， etc. CONCLUSIONS When using acalabrutinib， in addition to paying attention to the ADE recorded in its instructions， the risk of serious ADE that may lead to death， such as sudden cardiac death and pulmonary toxicity， should also be evaluated to avoid or reduce the occurrence of ADE as much as possible.