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 investigate the current situation of the use of transjugular intrahepatic portosystemic shunt (TIPS) for portal hypertension, which should aid the development of TIPS in China.Methods:The China Portal Hypertension Alliance (CHESS) initiated this study that comprehensively investigated the basic situation of TIPS for portal hypertension in China through network research. The survey included the following: the number of surgical cases, main indications, the development of Early-TIPS, TIPS for portal vein cavernous transformation, collateral circulation embolization, intraoperative portal pressure gradient measurement, commonly used stent types, conventional anticoagulation and time, postoperative follow-up, obstacles, and the application of domestic instruments.Results:According to the survey, a total of 13 527 TIPS operations were carried out in 545 hospitals participating in the survey in 2021, and 94.1% of the hospital had the habit of routine follow-up after TIPS. Most hospitals believed that the main indications of TIPS were the control of acute bleeding (42.6%) and the prevention of rebleeding (40.7%). 48.1% of the teams carried out early or priority TIPS, 53.0% of the teams carried out TIPS for the cavernous transformation of the portal vein, and 81.0% chose routine embolization of collateral circulation during operation. Most of them used coils and biological glue as embolic materials, and 78.5% of the team routinely performed intraoperative portal pressure gradient measurements. In selecting TIPS stents, 57.1% of the hospitals woulel choose Viator-specific stents, 57.2% woulel choose conventional anticoagulation after TIPS, and the duration of anticoagulation was between 3-6 months (55.4%). The limitation of TIPS surgery was mainly due to cost (72.3%) and insufficient understanding of doctors in related departments (77.4%). Most teams accepted the domestic instruments used in TIPS (92.7%).Conclusions:This survey shows that TIPS treatment is an essential part of treating portal hypertension in China. The total number of TIPS cases is far from that of patients with portal hypertension. In the future, it is still necessary to popularize TIPS technology and further standardize surgical indications, routine operations, and instrument application.

Objective:To establish and validate a prediction model for the risk of major upper gastrointestinal bleeding in patients with varices of liver cirrhosis.Method:This study retrospectively collected the clinical data of patients with esophageal and gastric variceal bleeding who were admitted to the emergency department of Ningxia Medical University General Hospital from October 2019 to October 2022. The patients were divided into modeling group and validation group according to the ratio of 7:3 by random number table method. The observation index was whether the upper gastrointestinal bleeding occurred within 24 hours after admission. The predictors in the logistic regression model were used to construct a prediction model for the risk of major upper gastrointestinal bleeding in patients with varices with liver cirrhosis, and the area under the receiver operating characteristic curve (AUC), the correction curve and the decision curve were analyzed to evaluate the discriminatory ability, accuracy and clinical utility of the prediction model.Results:A total of 305 patients were included, including 215 and 90 in the modeling and validation groups, respectively, and the clinical data of the two groups were comparable. Multivariate logistic regression showed that systolic blood pressure ( OR=0.918, 95% CI: 0.860-0.980, P=0.010), MAP(ASH) score ( OR=1.993, 95% CI: 1.017-3.907, P=0.045), Child-Pugh score ( OR=1.999, 95% CI: 1.139-3.510, P=0.016) and model for end-stage liver disease (MELD) ( OR=1.398, 95% CI: 1.037-1.886, P=0.028) were independent influencing factors for the occurrence of upper gastrointestinal bleeding in patients with liver cirrhosis varices. The AUC of the prediction model in the modeling group was 0.936 (95% CI: 0.895-0.976), and that of the prediction model in the validation group was 0.891 (95% CI: 0.807-0.975), the prediction model had good identification, calibration, and clinical application value. Conclusions:Systolic blood pressure, MAP (ASH) score, Child-Pugh score, and prediction models constructed by end-stage liver disease models are helpful for early prediction of the risk of upper gastrointestinal bleeding in patients with cirrhosis varices in the emergency department.

OBJECTIVE To understand the polypharmacy burden and influencing factors of elderly tuberculosis （TB） in Guizhou province， and to provide reference for reducing the polypharmacy burden of patients. METHODS From April to July 2022， 405 elderly TB outpatients were selected from three designated TB hospitals in Guiyang City， Bijie City， and Qiandongnan Miao and Dong Autonomous Prefecture of Guizhou Province by convenience sampling method as investigation objects. The general situation questionnaire and the Living with Medicines Questionnaire （LMQ） were used for face-to-face survey. Descriptive analysis， one-way ANOVA and multivariate linear regression analysis were used to understand the score of polypharmacy burden of elderly TB patients and explore the factors effecting polypharmacy burden in TB patients. RESULTS The total polypharmacy burden score of 405 elderly TB patients was （112.65±14.59） points， which was higher than the threshold （110 points） for high burden standard in LMQ. Multivariate linear regression analysis showed that aged 80 to 92 years， self-financed+medical insurance， retreatment， drug resistance， and adverse drug reactions were the risk factors for polypharmacy burden in elderly TB patients （P＜0.05）； living in the city， family member management， volunteer management and intelligent tool-assisted management were the protective factors （P＜0.05）. CONCLUSIONS The burden of polypharmacy in elderly TB patients from Guizhou province is heavy， and is influenced by patient’s age， residence， payment method， treatment classification， drug resistance， adverse drug reactions， and medication management. It is recommended that medical staff should provide key populations with medication guidance based on influential factor for polypharmacy burden so as to reduce their polypharmacy burden.

Objective:To investigate the safety and feasibility of the CHESS endoscpic ruler (CHESS ruler), and the consistency between the measured values and the interpretation values by endoscopic physician experience.Methods:From January 2021 to January 2022, a total of 105 liver cirrhosis patients with portal hypertension were prospectively enrolled from General Hospital, Xixia Branch Hospital, Ningnan Hospital of People′s Hospital of Ningxia Hui Autonomous Region (29 cases), and the First People′s Hospital of Yinchuan (25 cases), General Hospital of Ningxia Medical University (18 cases), Wuzhong People′s Hospital (10 cases), the Fifth People′s Hospital of Ningxia Hui Autonomous Region (10 cases), Shizuishan Second People′s Hospital (6 cases), Yinchuan Second People′s Hospital (5 cases), and Zhongwei People′s Hospital (2 cases) 8 hospitals. The clinical characteristics of all the patients, including gender, age, nationality, etiolog of liver cirrhosis, and Child-Pugh classification of liver function were recorded. A big gastroesophageal varices was defined as diameter of varices ≥5 mm. Endoscopist (associated chief physician) performed gastroscopy according to the routine gastroscopy procedures, and the diameter of the biggest esophageal varices was measured by experience and images were collected, and then objective measurement was with the CHESS ruler and images were collected. The diameter of esophageal varices of 10 randomly selected patients (random number table method) was determined by 6 endoscopists (attending physician or associated chief physician) with experience or measured by CHESS ruler. Kappa test was used to test the consistency in the diameter of esophageal varices between measured values by CHESS ruler and the interpretation values by endoscopic physician experience.Results:Among 105 liver cirrhosis patients with portal hypertension, male 65 cases and female 40 cases, aged (54.8±12.2) years old, Han nationality 82 cases, Hui nationality 21 cases and Mongolian nationality 2 cases. The etiology of liver cirrhosis included chronic hepatitis B (79 cases), alcoholic liver disease (7 cases), autoimmune hepatitis (7 cases), chronic hepatitis C (2 cases), and other etiology (10 cases). Liver function of 32 cases was Child-Pugh A, Child-Pugh B 57 cases, and Child-Pugh C 16 cases. All 105 liver cirrhosis patients with cirrhotic portal hypertension were successfully measured the diameter of gastroesophageal varices by CHESS ruler, and the success rate of application of CHESS ruler was 100.0% (105/105). The procedure time from the CHESS ruler into the body to the exit of the body after measurement was (3.50±2.55) min. No complications happened in all the patients during measurement. Among 105 liver cirrhosis patients with cirrhotic portal hypertension, 96 cases (91.4%) were recognized as big gastroesophageal varices by the endoscopists. Totally 93 cases (88.6%) were considered as big gastroesophageal varices by CHESS ruler. Eight cases were recognized as big gastroesophageal varices by the endoscopist, however not by the CHESS ruler; 5 cases were recognized as big gastroesophageal varices by the CHESS ruler, but not by the endoscopists; 4 cases were not recognized as big gastroesophageal varices both by the endoscopists and CHESS ruler; 88 cases were recognized as big gastroesophageal varices both by the endoscopists and CHESS ruler. The missed diagnostic rate of big gastroesophageal varices by the endoscopists experience was 5.4% (5/93), and the Kappa value of consistency coefficient between the measurement by the CHESS ruler and the interpretation by endoscopists experience was 0.31 (95% confidence interval 0.03 to 0.60). The overall Kappa value of consistency coefficient by 6 endoscopists measured by CHESS ruler in big gastroesophageal varices diagnosis was 0.77 (95% confidence interval 0.61 to 0.93).Conclusion:As an objective measurement tool, CHESS ruler can make up for the deficiency of subjective judgment by endoscopists, accurately measure the diameter of gastroesophageal varices, and is highly feasible and safe.

Progressive functional deterioration in the cochlea is associated with age-related hearing loss (ARHL). However, the cellular and molecular basis underlying cochlear aging remains largely unknown. Here, we established a dynamic single-cell transcriptomic landscape of mouse cochlear aging, in which we characterized aging-associated transcriptomic changes in 27 different cochlear cell types across five different time points. Overall, our analysis pinpoints loss of proteostasis and elevated apoptosis as the hallmark features of cochlear aging, highlights unexpected age-related transcriptional fluctuations in intermediate cells localized in the stria vascularis (SV) and demonstrates that upregulation of endoplasmic reticulum (ER) chaperon protein HSP90AA1 mitigates ER stress-induced damages associated with aging. Our work suggests that targeting unfolded protein response pathways may help alleviate aging-related SV atrophy and hence delay the progression of ARHL.
Mice ; Animals ; Transcriptome ; Aging/metabolism* ; Cochlea ; Stria Vascularis ; Presbycusis

Detailed characterizations of genomic alterations have not identified subtype-specific vulnerabilities in adult gliomas. Mapping gliomas into developmental programs may uncover new vulnerabilities that are not strictly related to genomic alterations. After identifying conserved gene modules co-expressed with EGFR or PDGFRA (EM or PM), we recently proposed an EM/PM classification scheme for adult gliomas in a histological subtype- and grade-independent manner. By using cohorts of bulk samples, paired primary and recurrent samples, multi-region samples from the same glioma, single-cell RNA-seq samples, and clinical samples, we here demonstrate the temporal and spatial stability of the EM and PM subtypes. The EM and PM subtypes, which progress in a subtype-specific mode, are robustly maintained in paired longitudinal samples. Elevated activities of cell proliferation, genomic instability and microenvironment, rather than subtype switching, mark recurrent gliomas. Within individual gliomas, the EM/PM subtype was preserved across regions and single cells. Malignant cells in the EM and PM gliomas were correlated to neural stem cell and oligodendrocyte progenitor cell compartment, respectively. Thus, while genetic makeup may change during progression and/or within different tumor areas, adult gliomas evolve within a neurodevelopmental framework of the EM and PM molecular subtypes. The dysregulated developmental pathways embedded in these molecular subtypes may contain subtype-specific vulnerabilities.
Humans ; Brain Neoplasms/pathology* ; Neoplasm Recurrence, Local/metabolism* ; Glioma/pathology* ; Neural Stem Cells/pathology* ; Oligodendrocyte Precursor Cells/pathology* ; Tumor Microenvironment

Objective:To evaluate the hemostatic efficacy of N-carboxyethylchitosan fiber gauze (numbered NWL-K) in a leporine bleeding wounds of intraperitoneal parenchymal visceral.Methods:Sixty New Zealand rabbits were divided into two groups according to the randomized digital number method, with 30 rabbits per group. The leporine bleeding models of hepatic or splenic wound were made respectively. The two groups were subdivided into three groups: common gauze group, SURGICEL group and NWL-K group, with 10 rabbits per group. By analyzing the weight of excised liver tissue and amount of bleeding, the model stability was measured. The time to hemostasis and bleeding score in each group were analyzed every (20±5)seconds after compression for 30 seconds in the hepatic bleeding models or every (30±5)seconds after compression for 3 minutes in the splenic bleeding models. The adhesion between wound and gauze was evaluated at the same time.Results:There was no significant difference in the weight of excised liver tissue and amount of bleeding when the hepatic or splenic bleeding models were made ( P>0.05). It showed that the model was made stably and the hemostasis experiment would not be affected. In the splenic wound model experiment, the time to hemostasis was 255(233, 300)seconds in SURGICEL group and 210(180, 248)seconds in NWL-K group, both of which were significantly shorter than 465(383, 660)seconds in common guaze group ( P<0.05). NWL-K achieved shorter time to hemostasis than SURGICEL ( P<0.05). In the hepatic wound model experiment, the time to hemostasis was 90(85, 110)seconds in SURGICEL group and 70(70, 95)seconds in NWL-K group, both of which were significantly shorter than 250(225 290)seconds in common gauze group ( P<0.05). In the splenic wound model experiment, the bleeding score in NWL-K group and SURGICEL group decreased faster than that in common gauze group ( P<0.05). The difference of bleeding score was significant between NWL-K group and SURGICEL group at 180 seconds ( P<0.05). In the hepatic wound model experiment, the bleeding score in NWL-K group and SURGICEL group decreased faster than that in common gauze group at 50 seconds, 70 seconds and 90 seconds ( P<0.05). The bleeding score in common gauze group and NWL-K group showed significant difference at 30 seconds, 110 seconds and 130 seconds ( P<0.05). For the adhesion evaluation, both the water-absorbency and adhesion to tissue of NWL-K were better than common gauze and SURGICEL. Conclusions:For hepatic and splenic bleeding wounds, compared with other types of gauze, the application of NWL-K can effectively shorten the time to hemostasis and reduce the blood loss. The NWL-K shows high water-absorbency and firm adhesion to bleeding wound.