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 Given that the PI3K/AKT/mTOR signaling pathway is associated with the progression of knee osteoarthritis(KOA),this study aims to investigate whether the polarization induction of synovial macrophages mediated by the PI3K/AKT/mTOR signaling axis is the cause of KOA progression.Methods The synovial fluid of KOA KL-Ⅱ and KL-Ⅲ patients and normal individuals was collected,and the percentage of M1 macrophages(CD80,CD86)and M2 macrophages(CD163,CD206)in the synovial fluid(M1/M2 ratio)was measured to e-valuate the polarization of macrophage cytokines such as IL-1,IL-6,IL-10,and tumor necrosis factor(TNF)-α,transforming growth factor(TGF)-β Expression in KOA synovial fluid,and detect and analyze of key molecules PI3K/AKT/mTOR signaling axis PI3K,AKT3,mTORC1,and inducible nitric oxide synthase(iONS)in KOA synovial fluid.Results Compared with the synovial fluid of normal individuals,the percentage of M1 macrophages(CD80,CD86)in KOA patients increased(P<0.01),and the M1/M2 ratio increased(P<0.001);The ex-pression of IL-1,IL-6,and TNF-α in the synovial fluid of the KOA group was also higher than that of the control group(P<0.01),while the expression of IL-10 and TGF-β in the KOA group was significantly reduced(P<0.01);The key proteins PI3K,AKT3,mTORC1,and downstream inflammatory factor iONS in the PI3K/AKT/mTOR signaling pathway in the synovial fluid of the KOA group were higher than those in the control group(P<0.01).Conclusion In KOA synovial fluid,M1 macrophage polarization plays a dominant role,and the inflam-matory response mediated by M1 macrophage polarization may be the cause of synovitis.At the same time,the PI3K/AKT/mTOR signaling pathway may mediate the polarization of M1 macrophages involved in KOA inflammato-ry response.

Gliomas tend to have a poor prognosis and are the most common primary malignant tumors of the central nervous system. Compared with patients with other cancers, glioma patients often suffer from increased levels of psychological stress, such as anxiety and fear. Chronic stress (CS) is thought to impact glioma profoundly. However, because of the complex mechanisms underlying CS and variability in individual tolerance, the role of CS in glioma remains unclear. This review suggests a new proposal to redivide the stress system into two parts. Neuronal activity is dominant upstream. Stress-signaling molecules produced by the neuroendocrine system are dominant downstream. We discuss the underlying molecular mechanisms by which CS impacts glioma. Potential pharmacological treatments are also summarized from the therapeutic perspective of CS.

Objective·To explore EDAR(ectodysplasin A receptor)gene variants that lead to congenital tooth agenesis,and preliminarily analyze the reasons why variants in EDAR can cause both syndromic and non-syndromic tooth agenesis.Methods·Patients with congenital tooth agenesis admitted to the Department of 2nd Dental Center,Shanghai Ninth People's Hospital,Shanghai Jiao Tong University School of Medicine and their family members were included,and genomic DNA from their peripheral blood was extracted for whole exome sequencing(WES).After preliminary screening,PolyPhen-2,Mutation Taster,and Provean were used to predict the harmfulness of potential variants.The screened variants in patients and their families were verified by Sanger sequencing.Conservation analysis of variants was performed,and Swiss-Model was used to analyze the changes in the three-dimensional structure of EDAR.The teeth and syndromic phenotype of the patients and their family members were investigated.Results·Among the included congenital tooth agenesis patients,five patients with EDAR mutations were found,one with EDAR frameshift mutation c.368_369insC(p.L123fs)and the other four with EDAR missense mutations.Two of these four patients were diagnosed as non-syndromic tooth agenesis(NSTA),resulted from c.77C＞A(p.A26E)homozygous mutation and c.380C＞T(p.P127L)heterozygous mutation,respectively.The other two patients with two variants were diagnosed as hypohidrotic ectodermal dysplasia(HED).One compound heterozygous missense mutation patient carried EDAR c.77C＞T(p.A26V)from her father andEDAR c.1281G＞C(p.L427F)from her mother;the other patient with both EDAR and EDA mutations carried EDAR c.1138A＞C(p.S380R)heterozygous mutation and EDA c.1013C＞T(p.T338M)hemizygous mutation.Both variants were from his mother and were reported to be related with NSTA.Two of these missense mutations,EDAR c.1281G＞C(p.L427F)and EDAR c.77C＞A(p.A26E),had not been reported before.The missense mutations affected the protein's spatial conformation by altering the polarity,charge,or volume of the amino acid residues.The frameshift mutation caused a non-triplet base addition,which probably led to protein truncation or degradation.Conclusion·Two new EDAR missense mutations are discovered.An NSTA patients with EDAR homozygous mutations and an HED patient with both EDA and EDAR mutations are reported.It expands the understanding of pathogenic mechanisms of EDAR mutations causing HED and NSTA.

Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.

Objective To explore the relationship between magnetic resonance imaging (MRI)-short time inversion recovery (STIR) signal changes and computerized tomography (CT) fracture line types of osteoporotic vertebral fractures. Methods The clinical data and MRI as well as CT imaging signs of 108 patients with osteoporotic vertebral fractures were retrospectively analyzed. The types of CT fracture lines and CT values of patients changed by different MRI-STIR signals were compared. Results After MRI examination, a total of 121 vertebrae were fractured in the enrolled patients. STIR sequence showed 45 sections of black line signal, 36 sections of no homologous high signal and 40 sections of homologous high signal; CT showed that there were 51 cases of fracture line insertion, 33 cases of fracture cracking and 37 cases of microfracture. The positive rate of vertebral CT fracture line with intercalation type was significantly higher in patients with no homologous high signal and homologous high signal with MRI-STIR sequence (P < 0.05); the positive rate of vertebral CT fracture line with microfracture type in patients with homologous high signal on MRI-STIR sequence was significantly higher than that with black line signal and without homologous high signal (P < 0.05); the vertebral CT value of patients with black line signal shown in MRI-STIR sequence was significantly lower than that of patients without homologous high signal and homologous high signal (P < 0.05). Conclusion There is a certain correlation between the changes of MRI-STIR signal and the type of CT fracture line. Patients with STIR sequences showing black line signals have a higher risk of vertebral impingement fracture and a poor prognosis.

Objective To investigate the mutation characteristics and influencing factors of ethambutol(EMB)resistance gene of Mycobacterium tuberculosis in Guangxi Zhuang Autonomous region,and to provide evidence for molecular diagnosis and clinical treatment of tuberculosis.Methods A total of 655 strains of Myco-bacterium tuberculosis(52 ethambutol resistant strains and 603 ethambutol sensitive strains)were collected continuously from 30 TB drug resistance monitoring sites in Guangxi in 2018-2019,and the mutation characteristics and influencing factors of ethambutol resistant genes were analyzed by whole genome sequencing.Results Among 655 strains of Mycobacterium tuberculosis,54 strains had ethambutol drug resistance gene mutation,the mutation rate was 8.24%(54/655).Among 52 EMB-resistant strains detected by proportional method,21 had gene mutation,the mutation rate was 40.38%(21/52),and 33 of 603 EMB-sensitive strains had gene mutation,the mutation rate was 5.47%(33/603).The gene mutation rate in drug-resistant strains was higher than that in sensitive strains(χ2 = 77.133,P = 0.000).The coincidence rate of EMB drug resistance phenotype and gene mutation was 40.38%(21/52),and the results of the two tests were not highly consistent(Kappa = 0.343,P<0.001).The mutant genes of 54 strains were embA,embB and embC,and there were 20 mutant forms,among which 29 were mutated at unit point,accounting for 53.70%(29/54),and 25 were mutated at joint site,accounting for 46.30%(25/54).Among the unit point mutations,embB306(35.19%)had the highest mutation proportion,followed by embB497(5.56%)and embB406(3.70%).Among the joint site mutations,embC270+embB378 had the highest mutation proportion(22.22%),The second was embB306+embA-12(3.70%).Gender,anti-tuberculosis treatment history,genotype and MDR might be related to EMB gene mutation(χ2 = 9.388,P = 0.004;χ2 = 27.084,P = 0.000;χ2 = 6.671,P = 0.010;χ2 = 68.826,P = 0.000).Multivariate logistic regression analysis showed that male(OR = 6.150),retreatment(OR = 2.636)and multidrug resistance(OR = 7.333)may be risk factors for EMB resistance gene mutation,and Beijing genotype may be a protective factor for EMB resistance gene mutation(OR = 0.511).Conclusion EMB resistance of Mycobacterium tuberculosis is related to embA,embB and embC gene mutations,and the incidence of EMB resistance phenotype is not high.For male,retreatable,MDR-resistant,and non-Beijing genotype TB patients,attention should be paid to the mutation of the EMB resistance gene.

Objective: To observe the effects of the tofacitinib on interstitial lung disease( ILD) by regulating the JAK⁃STAT signaling pathway. Methods: Wistar rats were randomly divided into 4 groups:normal group , ILD group ,prednisone acetate group , and tofacitinib group. Except for the normal group , the other three groups were given 3mg/ml bleomycin solution for modeling. After 28 days of intragastric administration , the lung tissues of all rats were collected for hematoxylin⁃eosin staining ( HE) and Western blot ( WB) to detect the protein levels of JAK1 and STAT1;Enzyme⁃linked immunosorbent assay(ELISA) was used to detect tumor necrosis factor in rat serum (TNF) Ⅳ α , interleukin (IL) Ⅳ6 , IL⁃10 , IL⁃1β . Results : HE staining of lung tissue in ILD ,prednisone acetate group and tofacitinib group showed alveolar tissue thickening , alveolar wall capillary congestion , bronchial luminal epithelial cells shedding, and inflammatory cell exudation. The results of WB showed that JAK1 and STAT1 significantly increased in ILD group , and decreased in different degrees compared with ILD group , tofacitinib group and prednisone acetate group (P < 0. 05) . The ELISA results showed that the expressions of serum TNF⁃α , IL⁃6 and IL⁃1β in the ILD group were significantly higher than those in the normal group (P < 0. 01) . The expression of pine group decreased (P < 0. 05) , and the expression of IL⁃10 was the opposite. Conclusion Tofacitinib reduces lung tissue damage and the inflammatory response in the treatment of ILD by inhibiting the JAK⁃STAT pathway and down⁃regulating the expression of inflammatory factors TNF⁃α , IL⁃6 , IL⁃1β and up⁃regulating the anti⁃inflammatory factor IL⁃10.