ObjectiveTo investigate the main risk factors for liver cirrhosis in chronic hepatitis B （CHB） patients with high metabolic risk， to establish a noninvasive predictive model， and to compare the diagnostic efficiency of this model and other models including fibrosis-4 （FIB-4）， aspartate aminotransferase-to-platelet ratio index （APRI）， gamma-glutamyl transpeptidase-to-platelet ratio （GPR）， and Forns index. MethodsA total of 527 CHB patients with high metabolic risks who were admitted to The Second Affiliated Hospital of Guangxi Medical University from September 1， 2017 to October 31， 2022 were enrolled as subjects， and they were randomly divided into modeling group with 368 patients and validation group with 159 patients at a ratio of 7∶3. The LASSO regression analysis and the multivariate Logistic regression analysis were performed for the modeling group to identify independent risk factors， and a nomogram model was established. The receiver operating characteristic （ROC） curve， the calibration curve， and the decision curve analysis were used to validate the nomogram prediction model in the modeling group and the validation group and assess its discriminatory ability， calibration， and clinical practicability. The Delong test was used to compare the area under the ROC curve （AUC） of the nomogram prediction model and other models. ResultsThe multivariate Logistic regression analysis showed that prealbumin （odds ratio ［OR］ = 0.993， 95% confidence interval ［CI］： 0.988 — 0.999， P= 0.019）， thrombin time （OR=1.182， 95% CI： 1.006 — 1.385， P=0.047）， log₁₀ total bilirubin （TBil） （OR=1.710， 95%CI： 1.239 — 2.419， P=0.001）， and log₁₀ alpha-fetoprotein （AFP） （OR=1.327， 95%CI： 1.052 — 1.683， P=0.018） were independent influencing factors for liver cirrhosis in CHB patients with high metabolic risks. A nomogram model for risk prediction was established based on the multivariate analysis， which had an AUC of 0.837 （95%CI： 0.788 — 0.888）， a specificity of 73.5%， and a sensitivity of 84.7%， as well as a significantly higher diagnostic efficiency than the models of FIB-4 （0.739）， APRI （0.802）， GPR （0.800）， and Forns index （0.709） （Z=2.815， 2.271， 1.989， and 2.722， P=0.005， 0.017， 0.045， and 0.006）. ConclusionThe nomogram model established based on prealbumin， thrombin time， log₁₀ TBil， and log₁₀ AFP has a certain clinical application value.

Atopic dermatitis(AD)is the most common chronic inflammatory skin disease.For decades,the treatment of AD has been limited to local corticosteroid or calcineurin inhibitors,and light therapy or systemic immunosuppressive drug for moderate to severe AD patients.With the in-depth study of the pathogenesis of AD,many local and systemic targeted therapy drugs are being developed,which may change the treatment options of AD.This review combination with the latest clinical trials give a summarize on the type,mechanism,efficacy and safety of biological targeted therapy for AD,to provide a theoretical basis for the individualized treatment of AD.

Objectives:To establish a comprehensive system of Cardiovascular Academic Performance Evaluation(CAPE)and rank global TOP100 medical institutions in the fields of cardiovascular diseases(CVD). Methods:CVD-related terms were extracted from Medical Subject Headings(MeSH),Embase thesaurus(EMtrees)and International Classification of Diseases(ICD)by CVD-related professionals,as well as by librarians and information professionals.Terminology databases(named as Fuwai Subject Headings)were established,and nine sub-disciplines were proposed,including ischemic heart diseases,hypertension,vascular diseases,arrhythmia,pulmonary vascular diseases,heart failure,congenital heart diseases,cardiomyopathy,and valvular heart diseases.The mapping patterns of sub-discipline,cardiovascular terminology and entry terms were pre-defined.The CVD-related research literature published from January 1,2016 to December 31,2022 were retrieved from Web of Science,PubMed and Scopus.Based on this,metadata were fused and duplicates were excluded.Fuwai Subject Headings were searched and matched into four respects for each literature,including subject words,titles,keywords,and abstracts,which was used to generate an information table of"Position—CVD terminology—Frequency",and to calculate CVD correlation scores and sub-discipline scores.We standardized the names of medical institutions and scholars,and make a ranking system for CAPE based on original articles with strong cardiovascular correlation(correlation score≥4).When evaluating the science and technological performance for Chinese hospitals in cardiovascular diseases,National Natural Science Foundation Projects,authorized invention patents,prize achievements,research platforms,and registered data of drug clinical trials in Center for Drug Evaluation(CDE)were considered besides research papers. Results:During 2016 and 2022,1 545 103 CVD research literatures were found worldwide.After excluding meeting abstracts,books,biographies,news,videos,audio texts,retracted publications,and corrections,1 178 019 CVD research literatures were further evaluated.518 058 literatures were indexed as"strongly correlated to CVD"using Fuwai Subject Headings.Besides papers,other data sources were also collected,including 11 143 CVD-related Natural Science Foundation Projects,19 382 CVD-related effective authorized invention patents,103 CVD-related national prize achievements,24 CVD-related national research platforms,and 2 084 CDE registered data of CVD-related drug clinical trials.Research teams from nine sub-disciplines reviewed and validated research literature in respective fields,and classification rules of corresponding sub-disciplines were created and improved based on their opinions.Finally,eleven individual indexes were chosen to construct CAPE system for ranking global TOP100 medical institutions in overall CVD field and TOP30 in nine sub-disciplines.From 2016 to 2022,the number of cardiovascular disease research papers published by Chinese institutes has increased by 123.5%,with a total of approximately 76.8 thousands papers published(about 30 papers per day on average),ranked the second under the United States(approximately 114.1 thousands papers).However,the proportion of papers published by the Chinese Journal Citation Reports(JCR)and the Chinese Academy of Sciences only ranked eighth in the world.In the comprehensive academic performance of original cardiovascular research papers in global hospitals from 2020 to 2022,only two Chinese medical institutions ranked in the TOP20 as evaluated by CAPE system. Conclusions:Based on multi-source data from 2016 to 2022,CAPE initiated to establish a cardiovascular academic performance evaluation system.

The toad, known for its various medicinal properties including parotid gland secretion (toad venom), dried skin, and gallbladder (toad bile), holds considerable medicinal applications as a valuable traditional Chinese animal medicine. Currently, in-depth attentions have been paid to the chemical composition and pharmacological properties of toad venom and skin; however, a lesser number of detailed analyses were concentrated on the toad bile. This review provides an overview of the chemical constituents in the bile of the Bufo genus, with a special focus on the cholestane and bufadienolides, and highlights the progress in their biosynthetic pathway and pharmacological activities. The analysis uncovers a distinct category of unsaturated Δ²² or Δ²³-C₂₇/C₂₈ bile acids in the toad gallbladder, potentially acting as key intermediaries in forming C-17 α-pyrone of bufadienolides. Furthermore, the high presence of 3α-OH configured bufadienolides in toad bile, in contrast to the common 3β-OH configured found in toad venom or skin, indicates a possible link between their minimal toxicity and the toad's self-defensive or physiological control. This review provides scientific basis for the development and utilization of toad bile resources, and provides useful reference for the discovery of lead compounds, analysis of the biosynthetic pathway of bufadienolides, and research on toad physiology.

Objective To investigate the role of endoplasmic reticulum stress and p38 mitogen-activated protein kinase P38MAPK signaling pathway in thyroid epithelial cell injury induced by high iodine.Methods The thyroid epithelial cells Nthy-ori 3-1 were randomly divided into control group(normal culture),model group(40 mmol·L-1 potassium iodide),4-phenylbutyric acid(4-PB A)group(40 mmol·L-1 potassium iodide and 2 mmol·L-1 4-PBA)and SB203580 group(40 mmol·L-1 potassium iodide and 10 μmol·L-1 SB203580).Western blot was used to detect the expression of glucose regulated protein 78(GRP78)and p-P38/P38 of Nthy-ori 3-1 cells.MTT and colony formation experiments were used to detect the proliferation level.Flow cytometry was used to detect the apoptosis level.Enzyme-linked immunosorbent assay(ELISA)was used to detect the level of interleukin-6(IL-6).Results The expression levels of GRP78 protein in control group,model group,4-PBA group and SB203580 group were 0.15±0.03,0.61±0.07,0.27±0.03 and 0.37±0.04;the ratios of p-P38/P38 were 0.12±0.03,0.53±0.04,0.35±0.04 and 0.25±0.03;cell survival rates were(100.00±0.00)％,(53.71±6.16)％,(80.24±8.17)％and(71.29±7.36)％;the number of clones formed was 271.36±25.18,96.09±10.79,183.24±15.36 and 141.24±16.18;the apoptosis rates were(1.04±0.21)％,(9.27±1.67)％,(3.18±1.52)％and(3.82±1.09)％;IL-6 secretion levels were(0.71±0.08),(9.17±0.87),(3.26±0.29)and(4.71±0.41)nmol·L-1,respectively.For the above indicators,there was significant difference between the model group and the control group(all P＜0.05);there was significant difference between the 4-PBA group,SB203580 group and the model group(all P＜0.05).Conclusion High iodine can inhibit the proliferation of Nthy-ori 3-1 cells and induce apoptosis and secretion of inflammatory factors,which may be related to the activation of endoplasmic reticulum stress and P38MAPK signaling pathway by high iodine.

Objective:To investigate the correlation between bone marrow microvascular density,angiogenesis factors and bortezomib resistance in multiple myeloma(MM).Methods:The data of 200 patients with MM treated in our hospital from January 2020 to August 2023 were retrospectively analyzed,and the patients with MM were divided into drug-resistant group(n=68)and non-drug-resistant group(n=132)according to their drug resistance during bortezomib treatment.The univariate and multivariate logistic analysis were used to screen the independent influencing factors of bortezomib resistance in MM patients during treatment.The receiver operating characteristic(ROC)curve and clinical decision curve(DCA)were used to evaluate the predictive performance and clinical application value of the risk prediction model,the consistency between the actual incidence rate and the predicted incidence rate was judged by validating the calibration chart,and the goodness-of-fit of the model was judged by H-L test.Results:68 of the 200 MM patients developed resistance and poor clinical efficacy during bortezomib treatment,and the clinical resistance rate of bortezomib was 34.0％.The results of multivariate analysis showed that high bone marrow microvessel density(MVD)and high bone marrow supernatant VEGF,HGF,and bFGF expression levels were independent risk factors for bortezomib resistance in MM patients(P＜0.05).The area under the ROC curve(AUC)of the model jointly constructed by bone marrow MVD,serum VEGF,HGF,bFGF and TNF-α levels was 0.924,and its sensitivity and specificity were 92.6％and 78.8％,which were higher than those of the bone marrow MVD model(AUC=0.743)and the vasogenesis factor model(AUC=0.878).The calibration curve of the joint prediction model was close to the standard curve,indicating that the model is more consistent.The results of H-L goodness-of-fit test showed x2=14.748,P=0.164,the joint prediction model had a good fit.The DCA curve showed that the clinical net benefit of intervention in the range of 0.0～1.0 was greater than that of full intervention and no intervention.Conclusion:The prediction model based on bone marrow MVD and vasogenesis factors(VEGF,HGF,bFGF)in MM patients has higher clinical evaluation performance and predictive value.

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 investigate the clinical effect of pulsed thulium laser(PTL)combined with triamcinolone acetonide injection in the treatment of failed posterior urethral anastomosis(FPUA).Methods:This retrospective study included 35 male pa-tients treated in Gongli Hospital for failed posterior urethral anastomosis from January 2018 to December 2023.All the patients under-went direct-vision internal urethrotomy(DVIU)with transurethral PTL(the PTL group,n=15)or transurethral plasma(the TUP group,n=20),and all received intralesional injection of triamcinolone acetonide.We followed up the patients for a median of 21 months,recorded the age,length of urethral stricture,operation time,pre-and post-operative maximum urinary flow rate(Qmax),postoperative complications and recurrence of urethral stricture,and compared the data obtained between the two groups.Results:All the patients smoothly completed the treatment procedures.No statistically significant differences were observed in the age,length of urethral stricture,operation time and postoperative complications between the two groups(P>0.05).The median follow-up time for the thulium laser group and plasma group was 21.0 months(IQR 16.0-24.0)and 21.0 months(IQR 17.0-25.0),respectively,with a statistically significant difference observed in the maximum urine flow rate before and after surgery at the 12-month mark(P<0.01).No significant disparity was found in terms of relapse-free survival between the two groups(P=0.398)Conclusion:Pulsed thulium laser combined with triamcinolone acetonide injection can effectively maintain a short-term cicatricial stability of the ure-thral stricture and satisfactory urethral patency,obviously superior to plasmotomy as a remedial treatment of urethral stricture after failed posterior urethral anastomosis.

Purpose: Molecular residual disease (MRD) is a promising biomarker in colorectal cancer (CRC) for prognosis and guiding treatment, while the whole-exome sequencing (WES) based tumor-informed assay is standard for evaluating MRD based on circulating tumor DNA (ctDNA). In this study, we assessed the feasibility of a fixed-panel for evaluating MRD in CRC. Materials and Methods: Seventy-five patients with resectable stage I-III CRC were enrolled. Tumor tissues obtained by surgery, and preoperative and postoperative day 7 blood samples were collected. The ctDNA was evaluated using the tumor-agnostic and tumor-informed fixed assays, as well as the WES-based and panel-based personalized assays in randomly selected patients. Results: The tumor-informed fixed assay had a higher preoperative positive rate than the tumor-agnostic assay (73.3% vs. 57.3%). The preoperative ctDNA status failed to predict disease-free survival (DFS) in either of the fixed assays, while the tumor-informed fixed assay-determined postoperative ctDNA positivity was significantly associated with worse DFS (hazard ratio [HR], 20.74; 95% confidence interval [CI], 7.19 to 59.83; p < 0.001), which was an independent predictor by multivariable analysis (HR, 28.57; 95% CI, 7.10 to 114.9; p < 0.001). Sub-cohort analysis indicated the WES-based personalized assay had the highest preoperative positive rate (95.1%). The two personalized assays and the tumor-informed fixed assay demonstrated same results in postoperative landmark (HR, 26.34; 95% CI, 6.01 to 115.57; p < 0.001), outperforming the tumor-agnostic fixed panel (HR, 3.04; 95% CI, 0.94 to 9.89; p=0.052). Conclusion Our study confirmed the prognostic value of the ctDNA positivity at postoperative day 7 by the tumor-informed fixed panel. The tumor-informed fixed panel may be a cost-effective method to evaluate MRD, which warrants further studies in future.

Objective: To evaluate the efficacy and safety of hybutimibe monotherapy or in combination with atorvastatin in the treatment of primary hypercholesterolemia. Methods: This was a multicenter, randomized, double-blind, double-dummy, parallel-controlled phase Ⅲ clinical trial of patients with untreated primary hypercholesterolemia from 41 centers in China between August 2015 and April 2019. Patients were randomly assigned, at a ratio of 1∶1∶1∶1∶1∶1, to the atorvastatin 10 mg group (group A), hybutimibe 20 mg group (group B), hybutimibe 20 mg plus atorvastatin 10 mg group (group C), hybutimibe 10 mg group (group D), hybutimibe 10 mg plus atorvastatin 10 mg group (group E), and placebo group (group F). After a dietary run-in period for at least 4 weeks, all patients were administered orally once a day according to their groups. The treatment period was 12 weeks after the first dose of the study drug, and efficacy and safety were evaluated at weeks 2, 4, 8, and 12. After the treatment period, patients voluntarily entered the long-term safety evaluation period and continued the assigned treatment (those in group F were randomly assigned to group B or D), with 40 weeks' observation. The primary endpoint was the percent change in low density lipoprotein cholesterol (LDL-C) from baseline at week 12. Secondary endpoints included the percent changes in high density lipoprotein cholesterol (HDL-C), triglyceride (TG), apolipoprotein B (Apo B) at week 12 and changes of the four above-mentioned lipid indicators at weeks 18, 24, 38, and 52. Safety was evaluated during the whole treatment period. Results: Totally, 727 patients were included in the treatment period with a mean age of (55.0±9.3) years old, including 253 males. No statistical differences were observed among the groups in demographics, comorbidities, and baseline blood lipid levels. At week 12, the percent changes in LDL-C were significantly different among groups A to F (all P<0.01). Compared to atorvastatin alone, hybutimibe combined with atorvastatin could further improve LDL-C, TG, and Apo B (all P<0.05). Furthermore, there was no significant difference in percent changes in LDL-C at week 12 between group C and group E (P=0.991 7). During the long-term evaluation period, there were intergroup statistical differences in changes of LDL-C, TG and Apo B at 18, 24, 38, and 52 weeks from baseline among the statins group (group A), hybutimibe group (groups B, D, and F), and combination group (groups C and E) (all P<0.01), with the best effect observed in the combination group. The incidence of adverse events was 64.2% in the statins group, 61.7% in the hybutimibe group, and 71.0% in the combination group during the long-term evaluation period. No treatment-related serious adverse events or adverse events leading to death occurred during the 52-week study period. Conclusions: Hybutimibe combined with atorvastatin showed confirmatory efficacy in patients with untreated primary hypercholesterolemia, which could further enhance the efficacy on the basis of atorvastatin monotherapy, with a good overall safety profile.
Male ; Humans ; Middle Aged ; Atorvastatin/therapeutic use* ; Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use* ; Hypercholesterolemia/drug therapy* ; Cholesterol, LDL/therapeutic use* ; Anticholesteremic Agents/therapeutic use* ; Treatment Outcome ; Triglycerides ; Apolipoproteins B/therapeutic use* ; Double-Blind Method ; Pyrroles/therapeutic use*