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 correlation between time in range (TIR) after short-term treatment and glycated hemoglobin after 3 months (HbA lc-3m) in patients with newly-diagnosed type 2 diabetes mellitus (T2DM). Methods:In this cross-sectional study, a total of 94 patients with newly-diagnosed T2DM who received treatment in the Department of Endocrinology of Inner Mongolia Autonomous Region People′s Hospital were enrolled from January 2018 to September 2022. The patients were followed-up for 3 months and had complete medical record. TIR was divided into three groups according to different target ranges of blood glucose (TIR1: TIR with blood glucose between 3.9 and 10.0 mmol/L, TIR2: TIR with blood glucose between 3.9 and 7.8 mmol/L, TIR3: TIR with fasting, premeal or bedtime blood glucose <6.1 mmol/L and 2 h postprandial blood glucose <8.0 mmol/L). The patients were divided into two groups based on whether their HbA 1c-3m level was less than 6.5%, and the baseline data and variations in TIR for distinct target glucose levels were compared between the two groups. Spearman′s correlation analysis and binary logistic regression analysis were used to analyze the relationship between baseline indicators, TIR after short-term treatment and HbA 1c-3m. Receiver operating characteristic curve (ROC) was drawn to evaluate the predictive ability of different TIR after short-term therapy for HbA 1c-3m. Results:There were statistically significant differences in TIR1 [81.0 (67.5, 94.6)% vs 71.4 (51.7, 85.7)%], TIR2 [57.7 (29.7, 70.8)% vs 40.9 (22.4, 52.3)%] and TIR3 [23.8 (10.2, 39.5)% vs 13.0 (4.8, 25.0)%] between patients with a HbA 1c-3m<6.5% and patients with a HbA 1c-3m≥6.5% (all P<0.05). Spearman correlation analysis showed that among all the patients with newly-diagnosed T2DM, TIR1, TIR2 and TIR3 were all negatively correlated with HbA 1c-3m [6.4 (6.1, 6.9)%] ( r=-0.322, -0.348, -0.303, respectively, all P<0.01). Logistic regression analysis showed that after adjusting for the confounding factors, TIR1 ( OR=1.021, 95% CI: 1.002-1.041; P=0.034), TIR2 ( OR=1.024, 95% CI: 1.006-1.043; P=0.011), TIR3 ( OR=1.037, 95% CI: 1.010-1.065; P=0.008) were all independently related to HbA 1c-3m. When HbA lc-3m<6.5% was taken as the target value, the area under the ROC curve: TIR1 was 0.639 (95% CI: 0.528-0.751), TIR2 was 0.671 (95% CI: 0.560-0.782), TIR3 was 0.659 (95% CI: 0.549-0.770), respectively. When HbA lc-3m<7.0% was taken as the target value, the area under the ROC curve: TIR1 was 0. 730 (95% CI: 0.619-0.841), TIR2 was 0.744 (95% CI: 0.642-0.846), TIR3 was 0.701 (95% CI: 0.588-0.814). There was no significant difference in the area among the three statistics ( P>0.05). Conclusions:For newly-diagnosed T2DM patients, TIR after short-term treatment is negatively correlated with HbA 1c after 3 months and has good predictive value for it.

Cinnamomi Ramulus and Alismatis Rhizoma are commonly used in the treatment of external-contraction diseases. Cinnamomi Ramulus is pungent， sweet， and warm， with the effects of ventilating lung and dispersing cold， warming Yang and transforming Qi， and promoting water and liquid flow from Taiyang meridian to remove dampness. Alismatis Rhizoma is sweet and cold， with the effects of draining dampness and promoting urination， regulating the waterway， removing water retention in lung， and promoting urination to remove dampness and heat. Herbal pairs are extracted from the accumulated experience of medical practitioners over the ages in the use of medicines and have been proved by clinical application to be composed of simple and effective combinations for specific diseases. The herb pair Cinnamomi Ramulus-Alismatis Rhizoma is an important part in ancient classic formulas such as Wulingsan. Both herbs play a role in draining dampness and promoting urination， warming Yang and transforming Qi， being a representative herb pair used for treating external-contraction exterior syndrome and water retention inside. The review of ancient medical publications revealed that there were a large number of compound formulas containing Cinnamomi Ramulus-Alismatis Rhizoma for dispersing cold and removing dampness， which were widely used for thousands of years in clinical practice. Modern pharmacological studies have shown that the active pharmacological components of Cinnamomi Ramulus （cinnamaldehyde and cinnamic acid） and Alismatis Rhizoma （alisol A and 23-acetate alisol B） have anti-inflammatory， antiviral， and immunoregulatory effects and high safety. Qingfei Paidu decoction containing this herbal pair played an important role in fighting against COVID-19. Despite the extensive pharmacological studies on Cinnamomi Ramulus and Alismatis Rhizoma， few studies have been carried out regarding this herb pair. This paper summarizes the traditional Chinese medicine knowledge about Cinnamomi Ramulus and Alismatis Rhizoma in the treatment of external-contraction diseases and summarizes the chemical composition， pharmacological effects， toxicology and other aspects of the two herbs before and after compatibility， aiming to provide a reference for further research and clinical application.

AIM:The effects and mechanisms of paeoniflorin(PF)on sepsis-associated acute kidney injury(SA-AKI)in mice were investigated based on cellular pyroptosis and the JNK/NEK7/NLRP3 pathway.METHODS:A murine SA-AKI model was established by intraperitoneal injection of lipopolysaccharide(LPS).Twenty-four male C57BL/6J mice aged 6～8 weeks were divided into four groups(n=6)using a randomized numerical table method:control(Con)group(an equal amount of DMSO-containing PBS was injected intraperitoneally at the same time);LPS group(LPS was injected intraperitoneally at 15 mg/kg);LPS+PF group(PF was injected intraperitoneally at 50 mg/kg for 30 min prior to modeling);and LPS+PF+anisomycin group(intraperitoneal injection of PF 50 mg/kg and JNK agonist anisomycin 20 mg/kg 30 min before modeling).Samples were taken 24 h after modeling.HE staining was used to observe the pathological changes in renal tissues,and Paller scoring of renal injury was performed.ELISA was used to detect the levels of renal in-jury markers:blood creatinine(Scr),kidney injury molecule 1(KIM-1),and the inflammatory factors interleukin 1β(IL-1β)and IL-18.Western blot was used to detect changes in phosphorylated c-Jun N-terminal kinase(p-JNK),NIMA-relat-ed expressed kinase 7(NEK7),nucleotide oligomerization domain(NOD)-like receptor protein 3(NLRP3),and N-ter-minal fragment of gasdermin D(GSDMD-N)protein levels.RESULTS:Compared with the Con group,HE staining in the LPS group showed congestion and edema in renal tissues,granular or cell-like tubular patterns in the dilated tubular lu-men of renal tubules,and congestion and edema in the renal interstitium.Paller scores,Scr,serum KIM-1,IL-1β,and IL-18 levels in renal tissues were elevated(P<0.05).The expression of p-JNK,NEK7,NLRP3,and GSDMD-N also in-creased(P<0.05).Compared with the LPS group,the LPS+PF group exhibited reduced renal histopathological injury,decreased Paller score,Scr,serum KIM-1,IL-1β,and IL-18 levels(P<0.05),and decreased protein expression of p-JNK,NEK7,NLRP3,and GSDMD-N(P<0.05).Compared with the LPS+PF group,the LPS+PF+anisomycin group showed increased renal histopathological injury,Paller score,Scr,serum KIM-1,IL-1β,and IL-18 levels(P<0.05),and increased expression of p-JNK,NEK7,NLRP3,and GSDMD-N(P<0.05).CONCLUSION:Paeoniflorin may at-tenuate SA-AKI by inhibiting the JNK/NEK7/NLRP3 signaling pathway and downregulating cellular pyroptosis.

Objective:To explore the compatibility and medication law of Cinnamomi Ramulus-Alismatis Rhizoma medicinal pair in ancient and modern prescriptions.Methods:Ancient prescriptions and Chinese patent medicines containing Cinnamomi Ramulus-Alismatis Rhizoma medicinal pair were retrieved from the database of ancient classic famous prescriptions 1.0 and the database of listed Chinese patent medicines 1.0 developed by the Institute of Information on Traditional Chinese Medicine, China Academy of Chinese Medical Sciences. Excel 2019 was used to establish a database. The ancient and modern medical record cloud platform V2.3.5 and SPSS Modeler 18.0 software were used to perform frequency statistics, association rule analysis, clustering analysis, etc. on the data.Results:Totally 79 ancient articles with Cinnamomi Ramulus-Alismatis Rhizoma medicinal pair were obtained, including 76 ancient prescriptions, involving 250 kinds of Chinese materia medica; 25 kinds of Chinese patent medicine were obtained, involving 186 kinds of Chinese materia medica. The drug properties of ancient prescriptions and modern TCM patent medicines were both mainly warm, cold and neutral. The main tastes of ancient prescriptions and modern Chinese patent medicines were pungent, sweet and bitter. And the drugs mainly belong to spleen, lung, liver and kidney meridians. Correlation analysis suggested the same high-frequency association compatibility of ancient and modern prescriptions, Poria-Cinnamomi Ramulus-Alismatis Rhizoma, Atractylodis Rhizoma-Cinnamomi Ramulus-Alismatis Rhizoma, Atractylodis Macrocephalae Rhizoma-Cinnamomi Ramulus-Alismatis Rhizoma. Both clinical symptoms and diseases associated with medicinal compatibility of ancient prescriptions were intestinal flora, edema and vomiting. The syndrome types included bladder impoundment, dampness trapped in the guardian surface, internal retention of phlegm and morbid fluid. The clinical symptoms associated with medicinal compatibility of modern TCM patent medicine were limb joints pain and edema. The diseases included rheumatic arthritis (RA) and kidney disease. The syndrome types included wind-cold-dampness RA, stagnation of collaterals and kidney yang deficiency. High frequency drug clustering yielded 4 clustered squares.Conclusion:The core indications treated by Cinnamomi Ramulus-Alismatis Rhizoma are exogenous diseases with dampness caused by syndrome types including internal storage of water-dampness, cold-dampness obstruction and so on, which can provide reference for further in-depth research and guidance on clinical medication.

As an industrial chemical， bisphenol A is widely used in various food packaging materials. However， it is an endocrine disrupting chemical， which has estrogen activity and can cause certain damage to humans. So far， there are few studies on the detection of bisphenol A in self-heating food packaging materials， and there remains a lack of relevant standard. Therefore， it is necessary to establish a simple， sensitive and efficient method for the detection of bisphenol A in self-heating food. This study briefly introduces the pretreatment methods of bisphenol A， such as ultrasonic extraction， solid phase extraction， accelerated solvent extraction， and detection methods， such as gas chromatography-mass spectrometry， high performance liquid chromatography， fluorescent detection， and electrochemical detection.

OBJECTIVE: To explore the genetic basis for a child with congenital heart disease (CHD) and global developmental delay (GDD). METHODS: A child who was hospitalized at the Department of Cardiac Surgery of Fujian Children's Hospital on April 27, 2022 was selected as the study subject. Clinical data of the child was collected. Umbilical cord blood sample of the child and peripheral blood samples of his parents were collected and subjected to whole exome sequencing (WES). Candidate variant was verified by Sanger sequencing and bioinformatic analysis. RESULTS: The child, a 3-year-and-3-month-old boy, had manifested cardiac abnormalities and developmental delay. WES revealed that he had harbored a nonsense variant of c.457C>T (p.Arg153*) in the NONO gene. Sanger sequencing showed that neither of his parents has carried the same variant. The variant has been recorded by the OMIM, ClinVar and HGMD databases, but not in the normal population databases of 1000 Genomes, dbSNP and gnomAD. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), it was rated as a pathogenic variant. CONCLUSION The c.457C>T (p.Arg153*) variant of the NONO gene probably underlay the CHD and GDD in this child. Above finding has expanded the phenotypic spectrum of the NONO gene and provided a reference for the clinical diagnosis and genetic counseling for this family.
Humans ; Male ; Computational Biology ; DNA-Binding Proteins ; Genetic Counseling ; Genomics ; Heart Defects, Congenital/genetics* ; Mutation ; Parents ; RNA-Binding Proteins ; Child, Preschool ; Developmental Disabilities/genetics*

AIM:To explore the effect of tomatidine(TA)on lipopolysaccharide(LPS)-induced nerve cell in-jury and the underlying mechanism.METHODS:The neuroinflammation model was induced by treating SH-SY5Y cells with LPS.These cells were divided into control(CON),LPS,and LPS+TA groups.The LPS group was treated with 5 μg/mL LPS for 24 h to establish an inflammatory model.The LPS+TA group was first treated with 5 μmol/L tomatidine for 24 h and then co-cultured with 5 μg/mL LPS for 24 h.Cell viability was detected using the CCK-8 assay.RT-qPCR was used to detect the mRNA expression of inflammatory factors tumor necrosis factor-α(TNF-α)and interleukin-1β(IL-1β).The protein expression of transcription factor EB(TFEB),p-TFEB,P62,and microtubule-associated protein 1 light chain 3(LC3)expression was detected through Western blot.TFEB localization and cleaved caspase-3 expression were detected through immunofluorescence.The cell apoptosis rate was detected through flow cytometry.RESULTS:(1)Compared with the CON group,the LPS group exhibited significant increases in IL-1β and TNF-α mRNA levels(P＜0.05),the cell apoptosis rate,and the p-TFEB level(P＜0.01).By contrast,P62,LC3-Ⅱ/LC3-Ⅰ,and TFEB protein ex-pression levels decreased significantly(P＜0.05),and TFEB was mainly localized in the cytoplasm.(2)Compared with the LPS group,tomatidine treatment significantly decreased the p-TFEB protein expression level(P＜0.01),increased the TFEB protein expression level(P＜0.01),and promoted the TFEB protein to migrate into the nucleus.After treatment of tomatidine,the LC3-Ⅱ/LC3-Ⅰ protein expression level significantly increased(P＜0.05),and the cell apoptosis rate signifi-cantly decreased(P＜0.01).In addition,the TNF-α mRNA level significantly decreased after tomatidine treatment(P＜0.01).CONCLUSION:Tomatidine improves autophagy dysfunction,inflammatory reaction,and cell apoptosis induced by LPS via activating the transcription factor EB.