Objective:To investigate the clinical efficacy and safety of heat-clearing and spleen-invigorating method in the treatment of Helicobacter pylori (Hp) initial treatment failure population.Methods:The clinical data of 155 patients with initial Hp failure in our hospital from January 2021 to December 2022 were retrospectively analyzed. According to the treatment plan, they were divided into TCM group (66 cases) and Western medicine group (89 cases). Python 3.70 was used for bias score matching (PSM) to obtain samples with balanced covariates between groups. Finally 66 pair of cases were successfully matched according to the propensity score and the 1:1 matching principle.The TCM group was given Yiqing Capsule + Jianpi Pills (4 weeks) as a course of treatment. The Western medicine group was given four anti-Hp remedial regimen, 2 weeks for 1 course. 2 groups were treated for 1 course. Hp was detected by 14C breath test and its clearance rate was calculated. The overall symptoms of functional dyspepsia (FD) were evaluated from four aspects: postprandial fullness, early satiety, middle and upper abdominal pain, and middle and upper abdominal burning sensation. The adverse reactions during treatment were observed and the clinical efficacy was evaluated. Results:After treatment, the Hp clearance rate was 75.76% (50/66) in the TCM group and 83.33% (55/66) in the Western medicine group, which was significantly improved compared with that before treatment, without statistical significance ( χ2=1.16, P=0.281). After treatment, the scores of fullness and discomfort after meal [1 (0,2) vs. (2,4), Z=-6.85], early satiety [2 (0,2) vs. 4 (4, 6), Z=-8.02], middle and upper abdominal pain [2 (2, 4) vs. 4 (4, 6), Z=-4.48] in the TCM group were lower than those in Western medicine group ( P<0.01). The total effective rate was 75.76% (50/66) in the TCM group and 69.70% (46/66) in the Western medicine group, without statistical significance ( χ2=2.00, P=0.573). No adverse reactions occurred in the 2 groups during treatment. Conclusion:In terms of heat-clearing and spleen-invigorating method for Hp initially failed patients, its Hp clearance rate and clinical total effective rate are comparable to Western medicine, and can effectively improve the clinical symptoms of patients with Hp initial treatment failure.

Objective To observe the therapeutic effects of urolithin A(UA)on respiratory syncytial virus(RSV)-induced lung infection in neonatal mice and explore the underlying mechanisms.Methods Babl/c mice(5-7 days old)were subjected to nasal instillation of RSV and received intraperitoneal injection of saline or 2.5,5 and 10 mg/kg UA 2 h after the infection and then once daily for 2 weeks.Bronchoalveolar lavage fluid(BALF)was then collected for detection of inflammatory cells and mediators,and lung pathology was evaluated with HE staining.RSV-infected BEAS-2B cells were treated with 2.5,5 or 10 μmol/L UA.Inflammatory factors,cell viability,apoptosis and autophagy were analyzed using ELISA,CCK-8 assay,TUNEL staining,flow cytometry,Western blotting and immunofluorescence staining.The cellular expressions of miR-136 and Sirt1 mRNAs were detected using qRT-PCR.A dual-luciferase reporter system was used to verify the binding between miR-136 and Sirt1.Results In neonatal Babl/c mice,RSV infection caused obvious lung pathologies,promoted pulmonary cell apoptosis and LC3-Ⅱ/Ⅰ,Beclin-1 and miR-136 expressions,and increased the total cell number,inflammatory cells and factors in the BALF and decreased p62 and Sirt1 expressions.All these changes were alleviated dose-dependently by UA.In BEAS-2B cells,RSV infection significantly increased cell apoptosis,LC3B-positive cells and miR-136 expression and reduced Sirt1 expression(P<0.01),which were dose-dependently attenuated by UA.Dual-luciferase reporter assay confirmed the binding between miR-136 and Sirt1.In RSV-infected BEAS-2B cells with UA treatment,overexpression of miR-136 and Ex527 treatment both significantly increased the inflammatory factors and cell apoptosis but decreased LC3B expression,and these changes were further enhanced by their combined treatment.Conclusion UA ameliorates RSV-induced lung infection in neonatal mice by activating miR-136-mediated Sirt1 signaling pathway.

Objective To observe the therapeutic effects of urolithin A(UA)on respiratory syncytial virus(RSV)-induced lung infection in neonatal mice and explore the underlying mechanisms.Methods Babl/c mice(5-7 days old)were subjected to nasal instillation of RSV and received intraperitoneal injection of saline or 2.5,5 and 10 mg/kg UA 2 h after the infection and then once daily for 2 weeks.Bronchoalveolar lavage fluid(BALF)was then collected for detection of inflammatory cells and mediators,and lung pathology was evaluated with HE staining.RSV-infected BEAS-2B cells were treated with 2.5,5 or 10 μmol/L UA.Inflammatory factors,cell viability,apoptosis and autophagy were analyzed using ELISA,CCK-8 assay,TUNEL staining,flow cytometry,Western blotting and immunofluorescence staining.The cellular expressions of miR-136 and Sirt1 mRNAs were detected using qRT-PCR.A dual-luciferase reporter system was used to verify the binding between miR-136 and Sirt1.Results In neonatal Babl/c mice,RSV infection caused obvious lung pathologies,promoted pulmonary cell apoptosis and LC3-Ⅱ/Ⅰ,Beclin-1 and miR-136 expressions,and increased the total cell number,inflammatory cells and factors in the BALF and decreased p62 and Sirt1 expressions.All these changes were alleviated dose-dependently by UA.In BEAS-2B cells,RSV infection significantly increased cell apoptosis,LC3B-positive cells and miR-136 expression and reduced Sirt1 expression(P<0.01),which were dose-dependently attenuated by UA.Dual-luciferase reporter assay confirmed the binding between miR-136 and Sirt1.In RSV-infected BEAS-2B cells with UA treatment,overexpression of miR-136 and Ex527 treatment both significantly increased the inflammatory factors and cell apoptosis but decreased LC3B expression,and these changes were further enhanced by their combined treatment.Conclusion UA ameliorates RSV-induced lung infection in neonatal mice by activating miR-136-mediated Sirt1 signaling pathway.

Objective:To screen the candidate genes in a patient with Kabuki syndrome (KS), providing basis for genetic counseling, prenatal screening, prenatal diagnosis and facilitating early treatment.Methods:This study included a 16-year-old female KS patient born of non-consanguineous Chinese parents who presented to Department of Orthognathic & Cleft Lip and Palate Plastic Surgery, School and Hospital of Stomatology, Wuhan University. Genomic DNA was extracted from the peripheral blood of the subjects and analyzed by whole-exome sequencing (WES). Sanger sequencing was performed to validate the mutation in the candidate gene. The conformational and physicochemical changes of the mutant were analyzed by Alphafold2, Antheprot and DOG.2.0.1, respectively. Distribution of KMT2D mutations in patients with KS was analyzed based on the Human Gene Mutation DatabaseResults:The proband manifested a typical KS facial gestalt, congenital cleft palate, fifth finger deformity, hypodontia, renal hypoplasia and hydronephrosis. Two de novo mutations c.[1166A>C; 1167dupC] (NM_003482) in cis on the same allele in the KMT2D gene were identified by WES and confirmed by allele-specific PCR. Bioinformatics analysis showed that three more α-helixes were added, and a (β-) turn and a (β-) sheet were reduced in KMT2D p. Y389S, p.V390Rfs*26 compared with the wild type. Meanwhile, the interceptive mutant-KMT2D protein p.V390Rfs*26 lost all four domains (FYRN domain, FYRC domain, SET domain, and PostSET domain), which may cause functional disabilities. Conclusions:Our study is the first to identify two novel and de novo KMT2D mutations in cis on the same allele in a KS patient and extends the KMT2D mutation spectrum of KS, providing evidence for genetic susceptibility counseling, prenatal screening and diagnosis, and early treatment of KS.

Objective:To investigate the correlation between levels of fibroblast growth factor-23 (FGF-23) and monocyte chemoattractant protein-1 (MCP-1) and glucocorticoids-induced osteoporosis (GIOP) in children.Methods:From May. 2018 to May. 2022, 80 children with glucocorticoid osteoporosis admitted to our hospital were selected as the study subjects, and the control group was 62 children who received glucocorticoid therapy but had normal bone mass. General data were collected and bone density and bone metabolism were measured, including type 1 collagen carboxy-terminal peptide (CTX-1), type 1 procollagen amino-terminal peptide (PINP), and osteocalcin (OC). The levels of MCP-1and FGF-23 in the serum of the two groups were detected, and univariate and multivariate analysis was performed using prism software to analyze the risk factors affecting GIOP.Results:There was no significant difference in general data between the two groups (both P>0.05). The levels of FGF-23 (264.81±24.61) and MCP-1 (194.16±15.76) in serum of GIOP children were significantly higher than those in the control group (207.97±9.91; 179.00±18.34) ( t=17.13, P < 0.001; t=5.29, P < 0.001) ; Compared with those of the control group (0.88±1.08; 23.98±2.45; 8.36±3.71; 4.56±2.21), bone mineral density (0.44±0.29), PINP (16.29±3.97) and OC (6.74±3.22) levels were decreased, and CTX-1 level was increased (6.62±1.11) ( t=3.58, P<0.05; t=13.40, P<0.05; t=2.78, P<0.05; t=7.25, P<0.05) of the study group. Multivariate Logistic regression model showed that FGF-23 ( OR=1.161, 95% CI: 1.080-1.341, P<0.05), MCP-1 ( OR=1.179, 95% CI: 1.044-1.448, P<0.05) and CTX-1 ( OR=3.018, 95% CI: 1.526-10.510, P<0.05) were independent clinical risk factors for GIOP in children (all P<0.05). PINP ( OR=0.453, 95% CI: 0.169-0.740, P<0.05) was a protective factor affecting GIOP in children. Conclusion:FGF-23 and MCP-1 were independent risk factors for GIOP in children.

OBJECTIVE To understand the safety of Ilaprazole sodium for injection in clinical practice. METHODS From Jan. 1st 2019 to Feb. 29th 2020， the data of 3 926 valid hospitalized patients receiving Ilaprazole sodium for injection were collected prospectively from 5 third-level hospitals through CHPS， and the post-marketing safety analysis was performed by using retrospective multicenter single cohort study. At the same time， a nested case-control study （the ratio of trial group and control group was 1∶4） was used to confirm the baseline stability of this study cohort and the correlation between adverse reactions and Ilaprazole sodium for injection. RESULTS Among 3 926 patients， 3 patients experienced 5 adverse drug events after using Ilaprazole sodium for injection， with the incidence of 0.076%. There was no serious adverse event， and the occurrence time was 2 days after medication； adverse drug events mainly include elevated liver function indicators （alanine transaminase， aspartate transaminase， total bilirubin）， which were mild and untreated， and all adverse drug events were improved. The results of the nested case-control study showed that the trial group and the control group belonged to the same background baseline， and the occurrence of adverse drug events was more closely related to Ilaprazole sodium for injection. CONCLUSIONS The overall safety of Ilaprazole sodium for injection is relatively high， and the occurrence of adverse events is more related to it.

Model informed precision dosing for warfarin is to provide individualized dosing by integrating information related to patient characteristics, disease status and pharmacokinetics /pharmacodynamics of warfarin, through mathematical modeling and simulation techniques based on the quantitative pharmacology. Compared with empirical dosing, it can improve the safety, effectiveness, economy, and adherence of pharmacotherapy of warfarin. This consensus report describes the commonly used modeling and simulation techniques for warfarin, their application in developing and adjusting dosing regimens, medication adherence and economy. Moreover, this consensus also elaborates the detailed procedures for the implementation in the warfarin pharmacy service pathway to facilitate the development and application of model informed precision dosing for warfarin.

Model informed precision dosing (MIPD) is a new concept to guide precision dosing for individual patient by modeling and simulation based on the available information about the individual patient, medications and the disease. Compared to the empirical dosing, MIPD could improve the efficacy, safety, economics and adherence of the pharmacotherapy according to the individual's pathophysiology, genotyping and disease progression. This consensus report provides a brief account of the concept, methodology and implementation of MIPD as well as clinical decision supporting systems for MIPD. The status and future advancing of MIPD was also discussed to facilitate the appropriate application and development of MIPD in China.

AIM: To study chronopharmacokinetics of helicid and its metabolites. METHODS: An HPLC-MS method for simultaneous determination of helicid and its three phase I metabolites were established and validated. At 8:00, 14:00 and 0:00, the rats were given helicid 50 mg/kg by gavage, respectively. Blood samples were collected from ophthalmic venous plexus. Then plasma concentration was measured. Pharmacokinetic behaviors of the original drug and its metabolites after administration at different time points were calculated and compared. RESULTS: This established HPLC-MS/MS method was successfully applied to simultaneous determination of helicid and its three metabolites in rat plasma after intragastric administration. Using AUC

Development of thoracolumbar vertebra (TLV) and rib primordium (RP) is a common evolutionary feature across vertebrates, although whole-organism analysis of the expression dynamics of TLV- and RP-related genes has been lacking. Here, we investigated the single-cell transcriptome landscape of thoracic vertebra (TV), lumbar vertebra (LV), and RP cells from a pig embryo at 27 days post-fertilization (dpf) and identified six cell types with distinct gene expression signatures. In-depth dissection of the gene expression dynamics and RNA velocity revealed a coupled process of osteogenesis and angiogenesis during TLV and RP development. Further analysis of cell type-specific and strand-specific expression uncovered the extremely high level of HOXA10 3'-UTR sequence specific to osteoblasts of LV cells, which may function as anti-HOXA10-antisense by counteracting the HOXA10-antisense effect to determine TLV transition. Thus, this work provides a valuable resource for understanding embryonic osteogenesis and angiogenesis underlying vertebrate TLV and RP development at the cell type-specific resolution, which serves as a comprehensive view on the transcriptional profile of animal embryo development.