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.

In order to judge the future development trend of science and technology, plan ahead and lay out the frontier technology fields and directions, China Association of Chinese Medicine(CACM) has launched consultation projects for collecting "major scienti-fic issues and engineering technology difficulties in traditional Chinese medicine(TCM)" for the industry for three consecutive years since 2019. Up to now, 18 projects have been selected as major issues for research, and some experience and achievements have been made. These projects have been applied in important scientific and technological work such as scientific and technological planning and deployment at all levels of national, local, and scientific research institutions, the selection and cultivation of major national scientific and technological projects, and the construction of innovation bases, giving full play to the role of the think tank advisory committee of CACM. This study reviewed the selection of major issues for the first time, systematically combed its application in the national layout of science and technology, and put forward the existing problems and improvement suggestions, aiming to provide new ideas for further improving the selection of major issues and research direction, providing a theoretical basis and decision support for the national scientific and technological layout in the field of TCM, and promoting scientific and technological innovation to facilitate the high quality development of TCM.
Medicine, Chinese Traditional ; Inventions ; China ; Drugs, Chinese Herbal

OBJECTIVE: To study the long-term clinical effect of multicenter multidisciplinary treatment (MDT) in children with renal malignant tumors. METHODS: A retrospective analysis was performed on the medical data of 55 children with renal malignant tumors who were diagnosed and treated with MDT in 3 hospitals in Hunan Province from January 2015 to January 2020, with GD-WT-2010 and CCCG-WT-2016 for treatment regimens. A Kaplan-Meier survival analysis was used to analyze the survival of the children. RESULTS: Of the 55 children, 10 had stage I tumor, 14 had stage Ⅱ tumor, 22 had stage Ⅲ tumor, 7 had stage IV tumor, and 2 had stage V tumor. As for pathological type, 47 had FH type and 8 had UFH type. All children underwent complete tumor resection. Of the 55 children, 14 (25%) received preoperative chemotherapy. All children, except 1 child with renal cell carcinoma, received postoperative chemotherapy. Among the 31 children with indication for radiotherapy, 21 (68%) received postoperative radiotherapy. One child died of postoperative metastasis. The incidence rate of FH-type myelosuppression was 94.4%, and the incidence rate of UFH-type myelosuppression was 100%. The median follow-up time was 21 months and the median survival time was 26 months for all children, with an overall survival rate of 98% and an event-free survival rate of 95%. CONCLUSIONS Multicenter MDT has the advantages of high success rate of operation and good therapeutic effect of chemotherapy in the treatment of children with renal malignant tumors, with myelosuppression as the most common side effects, and radiotherapy is safe and effective with few adverse events. Therefore, MDT has good feasibility, safety, and economy.
Child ; Family ; Humans ; Kidney Neoplasms/therapy* ; Progression-Free Survival ; Retrospective Studies

OBJECTIVE: To study the application value of whole exome sequencing (WES) in critically ill neonates with inherited diseases. METHODS: A total of 66 critically ill neonates with suspected inherited diseases or unclear clinical diagnosis who were admitted to the neonatal intensive care unit were enrolled as subjects. The clinical data of the neonates were collected, and venous blood samples were collected from the neonates and their parents for WES. The clinical manifestations of the neonates were observed to search for related pathogenic gene mutations. RESULTS: Among the 66 critically ill neonates with suspected inherited diseases or unclear clinical diagnosis (34 boys and 32 girls), 14 (21%) were found to have gene mutations by WES. One neonate had no gene mutation detected by WES but was highly suspected of pigment incontinence based on clinical manifestations, and multiplex ligation-dependent probe amplification detected a heterozygous deletion mutation in exons 4-10 of the IKBKG gene. Among the 15 neonates with gene mutations, 10 (67%) had pathogenic gene mutation, 1 (7%) was suspected of pathogenic gene mutation, and 4 (27%) had gene mutations with unknown significance. Among the 15 neonates, 13 underwent chromosome examination, and only 1 neonate was found to have chromosome abnormality. CONCLUSIONS Chromosome examination cannot be used as a diagnostic method for inherited diseases, and WES detection technology is an important tool to find inherited diseases in critically ill neonates with suspected inherited diseases or unclear clinical diagnosis; however WES technology has some limitation and it is thus necessary to combine with other sequencing methods to achieve an early diagnosis.
Critical Illness ; Exons ; Female ; Genetic Diseases, Inborn/genetics* ; Heterozygote ; Humans ; I-kappa B Kinase/genetics* ; Infant, Newborn ; Male ; Mutation ; Whole Exome Sequencing

This research aims to develop an UHPLC method, based on core-shell column(i.e. superficially porous particles), for simultaneous determination of eight isoflavonoids including formononetin,(6αR,11αR)-3-hydroxy-9,10-dimethoxypterocarpan, calycosin-7-O-β-D-glucopyranoside,(3R)-7,2-dihydroxy-3,4-dimethoxyisoflavone, calycosin, ononin,(6αR,11αR)-9,10-dimethoxypterocarpan-3-O-β-D-glucopyranoside, and(3R)-7,2-dihydroxy-3,4-dimethoxyisoflavan-7-O-β-D-glucopyranoside in Astragali Radix. The analysis was performed on an Agilent Poroshell EC-C_(18 )column(2.1 mm×100 mm, 2.7 μm) with 0.2% formic acid solution(A)-acetonitrile(B) as mobile phase for gradient elution. The flow rate was 0.5 mL·min~(-1), with column temperature of 40 ℃ and the wavelengths were set at 260 and 280 nm. According to the results, all calibration curves showed good linearity(R~2>0.999 8) within the tested concentration ranges. Both the intra-and inter-day precisions for 8 isoflavonoids were less than 0.80%, with the mean recovery at the range of 94.71%-104.6%. Thus, the newly developed UHPLC method using core-shell column owned the advantages in terms of rapid analysis, low column pressure and less solvent consumption, thus enabling the usage of conventional HPLC systems. Meanwhile, quantitative evaluation was carried out for 22 batches of commercial Astragali Radix. It has been found that great variations occurred for the content of the individual isoflavonoids among different batches; in contrast, the total content of total 8 isoflavonoids(>0.1%) was stable in most samples, indicating that it was reasonable to involve all isoflavonoids as the chemical markers for the quality control of Astragali Radix.
Astragalus Plant ; chemistry ; Chromatography, High Pressure Liquid ; Drugs, Chinese Herbal ; standards ; Flavones ; analysis ; Phytochemicals ; analysis ; Plant Roots ; chemistry ; Quality Control

OBJECTIVETo investigate the role of allograft inflammatory factor-1 (AIF-1) in colorectal cancer (CRC) progression and explore the possible mechanism.

METHODSThe expression levels of AIF-1 in 70 CRC tissues and paired adjacent tissues were detected using immunohistochemistry and Western blotting, and the correlation of AIF-1 expression with the clinicopathological features of the patients was analyzed. In the CRC cell line SW480, the functional role of AIF-1 in regulating tumor progression was investigated by transfecting the cells with an AIF-1-overexpressing plasmid (AIF-1) and a negative control plasmid (NC). EdU proliferation assay and flow cytometry were used to assess the cell proliferation and cell cycle changes; Transwell migration assay and Annexin V-APC/7-AAD apoptosis assay kit were used to analyze the cell migration and apoptosis. The changes in the biological behaviors of the cells were observed after application of SB203580 to block the p38 MAPK pathway. The expression levels of CDK4, cyclin D1, P21, P27, MMP2, MMP9, Bax, Bcl2, Bcl-xl, p38 and p-p38 were detected using Western blotting.

RESULTSAIF-1 was down-regulated in CRC tissues compared with the adjacent normal tissues, and its expression level was positively correlated with lymph node metastasis (P=0.008), TNM stage (P=0.003) and tumor size (P=0.023). Overexpression of AIF-1 in SW480 cells significantly reduced EdU-positive cells and caused obvious cell cycle arrest in G1 phase (P<0.05). AIF-1 overexpression resulted in significantly lowered protein expressions of CDK4 and cyclin D1, enhanced expressions of P21 and P27, attenuated cell migration ability (P<0.001), and decreased protein levels of MMP2 and MMP9. AIF-1 overexpression also induced obvious apoptosis of SW480 cells (P<0.01), significantly increased the protein levels of Bax and p-p38, and decreased the protein levels of Bcl-2 and Bcl-xl; SB203580 significantly attenuated the apoptosis-inducing effect of AIF-1 overexpression.

CONCLUSIONAIF-1 plays the role of a tumor suppressor in CRC by inhibiting cell proliferation, suppressing cell migration and inducing cell apoptosis. AIF-1 overexpression promotes the apoptosis of CRC cells by activating the p38 MAPK pathway.

Activation of acid-sensing ion channels (ASICs) plays an important role in neuroinflammation.Macrophage recruitment to the sites of inflammation is an essential step in host defense.ASIC 1 and ASIC3 have been reported to mediate the endocytosis and maturation of bone marrow derived macrophages.However,the expression and inflammation-related functions of ASICs in RAW 264.7 cells,another common macrophage,are still elusive.In the present study,we first demonstrated the presence of ASIC 1,ASIC2a and ASIC3 in RAW 264.7 macrophage cell line by using reverse transcriptase polymerase chain reaction (RT-PCR),Western blotting and immunofluorescence experiments.The non-specific ASICs inhibitor amiloride and specific homomeric ASIC 1 a blocker PcTx 1 reduced the production of iNOS and COX-2 by LPS-induced activating RAW 264.7 cells.Furthermore,not only amiloride but also PcTx 1 inhibited the migration and LPS-induced apoptosis of RAW 264.7 cells.Taken together,our findings suggest that ASICs promote the inflammatory response and apoptosis of RAW 264.7 cells,and ASICs may serve as a potential novel target for immunological disease therapy.

Objective To explore the relationship between human leukocyte antigen (HLA) DRB gene polymorphism and allergic reaction of anti-tuberculosis drugs in Chinese Han population.Methods HLA-DRB alleles in 35 patients with allergic reaction and 42 patients with no allergic reaction were analyzed using sequence-specific primer-polymerase chain reaction (PCR-SSP) method.Results The frequency of DR7 gene in allergy group was significantly higher than that in patients without allergic reaction group (10.0％ vs 1.2％,RR =10.25,P ＜0.05).Conclusion DR7 may be a susceptible gene for allergic reactions to anti-tuberculosis drugs.