OBJECTIVE: To evaluate the dynamic changes of glucocorticoid (GC) dose and the feasibility of GC discontinuation in rheumatoid arthritis (RA) patients under the background of Chinese medicine (CM). METHODS: This multicenter retrospective cohort study included 1,196 RA patients enrolled in the China Rheumatoid Arthritis Registry of Patients with Chinese Medicine (CERTAIN) from September 1, 2019 to December 4, 2023, who initiated GC therapy. Participants were divided into the Western medicine (WM) and integrative medicine (IM, combination of CM and WM) groups based on medication regimen. Follow-up was performed at least every 3 months to assess dynamic changes in GC dose. Changes in GC dose were analyzed by generalized estimator equation, the probability of GC discontinuation was assessed using Kaplan-Meier curve, and predictors of GC discontinuation were analyzed by Cox regression. Patients with <12 months of follow-up were excluded for the sensitivity analysis. RESULTS: Among 1,196 patients (85.4% female; median age 56.4 years), 880 (73.6%) received IM. Over a median 12-month follow-up, 34.3% (410 cases) discontinued GC, with significantly higher rates in the IM group (40.8% vs. 16.1% in WM; P<0.05). GC dose declined progressively, with IM patients demonstrating faster reductions (median 3.75 mg vs. 5.00 mg in WM at 12 months; P<0.05). Multivariate Cox analysis identified age <60 years [P<0.001, hazard ratios (HR)=2.142, 95% confidence interval (CI): 1.523-3.012], IM therapy (P=0.001, HR=2.175, 95% CI: 1.369-3.456), baseline GC dose ⩽7.5 mg (P=0.003, HR=1.637, 95% CI: 1.177-2.275), and absence of non-steroidal anti-inflammatory drugs use (P=0.001, HR=2.546, 95% CI: 1.432-4.527) as significant predictors of GC discontinuation. Sensitivity analysis (545 cases) confirmed these findings. CONCLUSIONS RA patients receiving CM face difficulties in following guideline-recommended GC discontinuation protocols. IM can promote GC discontinuation and is a promising strategy to reduce GC dependency in RA management. (Trial registration: ClinicalTrials.gov, No. NCT05219214).
Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Arthritis, Rheumatoid/drug therapy* ; Glucocorticoids/therapeutic use* ; Medicine, Chinese Traditional ; Retrospective Studies

Objective:To analyze the epidemiological characteristics of norovirus (NoV) acute gastroenteritis (AGE) outbreaks caused by GII.17[P17] variant in China, 2022.Methods:Information and specimens of AGE outbreaks between January and December 2022 were collected. NoV RNA was detected in all specimens by real-time RT-PCR. The viral genome of the positive specimens were amplified, sequenced and analyzed.Results:Between January and December 2022, 360 AGE outbreaks were reported cumulatively, of which 266 outbreaks successfully obtained genotype results. GII.17 [P17] was one of the main genotypes and detected in 34 outbreaks (12.78%, 34/266), with the highest number of outbreaks detected in spring (6 outbreaks in March and 7 outbreaks in May), mainly in childcare facilities and primary schools (61.76%, 21/34). According to the result of NoV genotype analysis in different age groups, 14 strains of GII.17 [P17] in this study belonged to Cluster III b and SC III branch of Cluster III (Kawasaki308) in the capsid region and polymerase region, respectively, and both belonged to the same cluster as the variant strain (GZ41621 strain) that caused the NoV AGE outbreaks in China during the 2014/15 season. Compared to reference strains of Cluster I, Cluster II and Cluster III a, Cluster III b was provided with 22 amino acid mutations in VP1. The main amino acid changes in the subgroup of Cluster III b including the virus strains isolated in this study were at T294I and Q299R of antigen epitope A, an insertion mutation occurred at antigen epitope D, H353Q at the site I of the human histo-blood group antigen receptor binding site. The selection pressure analysis detected a large number of negative selection sites, indicating that negative selection plays an important role in the evolution of VP1 genes.Conclusions:GII.17 [P17] was one of the primary genotypes responsible for NoV diarrhea outbreaks in China in 2022. Phylogenetic analysis had revealed that it still belonged to the same cluster as the novel GII.17 [P17] variant (strain GZ41621) that caused NoV epidemics in China during the 2014/15 season, exhibiting minor amino acid variations at the potential epitope.

Seven compounds were isolated from fermentation extract of cave-derived Metarhizium anisopliae NHC-M3-2 by silica gel, semi-preparative HPLC and other chromatographic methods. Their structures were elucidated by UV, IR, MS and NMR methods as 2,3-dehydroindigotide G (1), (-)-regiolone (2), naphtho-γ-pyrone (3), indigotide G (4), indigotide B (5) destruxin A (6) and destruxin B (7). Compound 1 is a new glycoside naphthopyranone compound. The anti-hepatitis B virus (HBV) activity of these compounds was evaluated. The EC₅₀ and CC₅₀ of compound 3 against HBV were 4.5 μmol·L^-1 and 92.3 μmol·L^-1, respectively. This is the first report of the antiviral activity of compound 3.

AIM:To evaluate the macular microstructural changes in patients with rhegmatogenous retinal detachment(RRD)after silicone oil tamponade by spectral-domain optical coherence tomography(SD-OCT).METHODS:From November 2019 to July 2021, 27 patients with 27 eyes in RRD who underwent vitrectomy combined with silicone oil tamponade in Cangzhou Aier Eye Hospital were enrolled in this study as the observation group, other 30 healthy volunteers with 30 eyes were included in the control group. The best corrected visual acuity(BCVA)of patients before and after operation were observed, and quantified evaluation of the postoperative macular microstructural changes were performed by SD-OCT.RESULTS: The BCVA(LogMAR)of the observation group at 1wk and 3mo after operation(0.61±0.23, 0.69±0.34)were improved compared with those before operation(1.43±0.77)(all P<0.01). The cube volume and average cube thickness in the macular area at 3mo after operation in the observation group were lower than those at 1wk and 1mo after operation in the control group(all P<0.05). There were no differences in the average ganglion cell-inner plexiform layer(GCIPL)thickness, minimum GCIPL thickness, average macular retinal nerve fiber layer(mRNFL)thickness and minimum mRNFL thickness at 1wk, 1 and 3mo after operation in the observation group, but all decreased compared with the control group(all P<0.01). There were 9 eyes with subretinal fluid(SRF)in the observation group during postoperative follow-up, SRF had a tendency to be gradually absorbed, but 1 eye had a secondary macular hole; 3 eyes had ellipsoid zone disruption, which had a tendency to be gradually repaired; 2 eyes had submacular perfluorocarbon liquid; 2 eyes had macular edema.CONCLUSION: SD-OCT can show the microstructure and morphological changes very well in macular area in patients with RRD after silicone oil tamponade, and has important clinical value for the preoperative and postoperative follow-up evaluation of RRD.

Objective: Transanal total mesorectal excision (taTME) was a very hot topic in the first few years since its appearance, but now more introspections and controversies on this procedure have emerged. One of the reasons why the Norwegian Ministry of Health stopped taTME was the high incidence of postoperative anastomotic leak. In current study, the incidence and risk factors of anastomotic leak after taTME were analyzed based on the data registered in the Chinese taTME Registry Collaborative (CTRC). Methods: A case-control study was carried out. Between November 15, 2017 and December 31, 2020, clinical data of 1668 patients undergoing taTME procedure registered in the CTRC database from 43 domestic centers were collected retrospectively. After excluding 98 cases without anastomosis and 109 cases without complete postoperative complication data, 1461 patients were finally enrolled for analysis. There were 1036 males (70.9%) and 425 females (29.1%) with mean age of (58.2±15.6) years and mean body mass index of (23.6±3.8) kg/m(2). Anastomotic leak was diagnosed and classified according to the International Study Group of Rectal Cancer (ISREC) criteria. The risk factors associated with postoperative anastomotic leak cases were analyzed. The impact of the cumulative number of taTME surgeries in a single center on the incidence of anastomotic leak was evaluated. As for those centers with the number of taTME surgery ≥ 40 cases, incidence of anastomic leak between 20 cases of taTME surgery in the early and later phases was compared. Results: Of 1461 patients undergoing taTME, 103(7.0%) developed anastomotic leak, including 71 (68.9%) males and 32 (31.1%) females with mean age of (59.0±13.9) years and mean body mass index of (24.5±5.7) kg/m(2). The mean distance between anastomosis site and anal verge was (2.6±1.4) cm. Thirty-nine cases (37.9%) were classified as ISREC grade A, 30 cases (29.1%) as grade B and 34 cases (33.0%) as grade C. Anastomotic leak occurred in 89 cases (7.0%,89/1263) in the laparoscopic taTME group and 14 cases (7.1%, 14/198) in the pure taTME group. Multivariate analysis showed that hand-sewn anastomosis (P=0.004) and the absence of defunctioning stoma (P=0.013) were independently associated with anastomotic leak after taTME. In the 16 centers (37.2%) which performed ≥ 30 taTME surgeries with cumulative number of 1317 taTME surgeries, 86 cases developed anastomotic leak (6.5%, 86/1317). And in the 27 centers which performed less than 30 taTME surgeries with cumulative number of 144 taTME surgeries, 17 cases developed anastomotic leak (11.8%, 17/144). There was significant difference between two kinds of center (χ(2)=5.513, P=0.019). Thirteen centers performed ≥ 40 taTME surgeries. In the early phase (the first 20 cases in each center), 29 cases (11.2%, 29/260) developed anastomotic leak, and in the later phase, 12 cases (4.6%, 12/260) developed anastomotic leak. The difference between the early phase and the later phase was statistically significant (χ(2)=7.652, P=0.006). Conclusion: The incidence of anastomotic leak after taTME may be reduced by using stapler and defunctioning stoma, or by accumulating experience.
Adult ; Aged ; Anastomotic Leak/etiology* ; Case-Control Studies ; China/epidemiology* ; Female ; Humans ; Incidence ; Laparoscopy ; Male ; Middle Aged ; Postoperative Complications/epidemiology* ; Rectal Neoplasms/surgery* ; Rectum/surgery* ; Retrospective Studies ; Risk Factors

OBJECTIVEThis study aimed at investigating whether notoginsenoside R1 (R1), a unique saponin found in Panax notoginseng could promote angiogenic activity on human umbilical vein endothelial cells (HUVECs) and elucidate their potential molecular mechanisms. In addition, vascular restorative activities of R1 was assessed in a chemically-induced blood vessel loss model in zebrafish.

METHODSThe in vitro angiogenic effect of R1 was compared with other previously reported angiogenic saponins Rg1 and Re. The HUVECs proliferation in the presence of R1 was determined by cell proliferation kit II (XTT) assay. R1, Rg1 and Re-induced HUVECs invasion across polycarbonate membrane was stained with Hoechst-33342 and quantified microscopically. Tube formation assay using matrigelcoated wells was performed to evaluate the pro-angiogenic actions of R1. In order to understand the mechanism underlying the pro-angiogenic effect, various pathway inhibitors such as SU5416, wortmannin (wort) or L-Nω-nitro- L-arginine methyl ester hydrochloride (L-NAME), SH-6 were used to probe the possible involvement of signaling pathway in the R1 mediated HUVECs proliferation. In in vivo assays, zebrafish embryos at 21 hpf were pre-treated with vascular endothelial growth factor (VEGF) receptor kinase inhibitor II (VRI) for 3 h only and subsequently post-treated with R1 for 48 h, respectively. The intersegmental vessels (ISVs) in zebrafish were assessed for the restorative effect of R1 on defective blood vessels.

RESULTSR1 could stimulate the proliferation of HUVECs. In the chemoinvasion assay, R1 significantly increased the number of cross-membrane HUVECs. In addition, R1 markedly enhanced the tube formation ability of HUVECs. The proliferative effects of these saponins on HUVECs were effectively blocked by the addition of SU5416 (a VEGF-KDR/Flk-1 inhibitor). Similarly, pre-treatment with wort [a phosphatidylinositol 3-kinase (PI3K)-kinase inhibitor], L-NAME [an endothelial nitric oxide synthase (eNOS) inhibitor] or SH-6 (an Akt pathway inhibitor) significantly abrogated the R1 induced proliferation of HUVECs. In chemicallyinduced blood vessel loss model in zebrafish, R1 significantly rescue the damaged ISVs.

CONCLUSIONR1, similar to Rg1 and Re, had been showed pro-angiogenic action, possibly via the activation of the VEGF-KDR/Flk-1 and PI3K-Akt-eNOS signaling pathways. Our findings also shed light on intriguing pro-angiogenic effect of R1 under deficient angiogenesis condition in a pharmacologic-induced blood vessels loss model in zebrafish. The present study in vivo and in vitro provided scientific evidence to explain the ethnomedical use of Panax notoginseng in the treatment of cardiovascular diseases, traumatic injuries and wound healing.

Animals ; Blood Vessels ; pathology ; Cell Movement ; drug effects ; Cell Proliferation ; drug effects ; Collagen ; pharmacology ; Disease Models, Animal ; Drug Combinations ; Ginsenosides ; chemistry ; pharmacology ; Human Umbilical Vein Endothelial Cells ; cytology ; drug effects ; enzymology ; physiology ; Humans ; Laminin ; pharmacology ; Neovascularization, Physiologic ; drug effects ; Phosphatidylinositol 3-Kinases ; metabolism ; Protein Kinase Inhibitors ; pharmacology ; Proteoglycans ; pharmacology ; Proto-Oncogene Proteins c-akt ; metabolism ; Vascular Endothelial Growth Factor Receptor-2 ; metabolism ; Zebrafish

Objective To investigate the prevalence and related factors of medicinal therapy in patients with chronic systolic heart failure (CSHF).Methods Data on in-hospital patients with CSHF were studied from 12 hospitals in Hubei province,in 2000 and 2010.Differences on gender and age were calculated and Multivariate Cox regression analysis was performed to determinate the independent risk factors of all-cause mortality.Results (1) 16 681 patients were enrolled in this study.Among which,6453 died during the 5.82 ± 1.63 years of follow-up.The annual medical expenditure was larger in the survival group than in the dead ones (3.19 ± 0.65 vs.3.32 ± 0.57,P＜0.01).(2)The prevalence of Angiotensin Ⅱ receptor blocker increased along with age which accounted as 7.73％,7.35％,12.26％,14.29％,17.19％,19.87％ and 20.49％,respectively,in the ＜30,30-39,40-49,50-59,60-69,70-79 and ≥80-year groups.The distribution of digitalis,diuretics,β-receptor blocker,Angiorensin- converting enzyke inhibitors showed inversed U shape.(3)The annual medical expenditure increased as patients got older,with age groups ＜30,30-39,40-49,50-59,60-69 and 70-79 years old as 2.96 ± 0.70,3.09 ± 0.62,3.15 ± 0.58,3.30 ± 0.59 and 3.25 ±0.58,respectively (P＜0.01).It reduced to the same level as in the 50-59 year-old group.The distribution of annual medical expenditure showed similar pattern in males.However,the trends were only found in patients at 50-59,60-69,70-79 and ≥80 years-old groups in female.Conclusion More attention should be paid to medicinal therapy in patients with CSHF.Medicinal therapy shifted with age and gender,of which females had more adverse trend than in males.

Objective To determinate the prognostic value of red cell distribution width (RDW) and the relationships between RDW and clinical characteristics in patients with chronic heart failure (CHF).Methods A total of 16 681 in-hospital patients with chronic systolic HF and LVEF ＜50％ from 12 hospitals in Hubei province,China were enrolled.All patients were followed up with telephone call.Patients were divided into RDW ≤ 13.2％ (n =3981 ),13.3％ - 14.1％ (n =3996),14.2％ - 14.8％ ( n =4319) and ≥14.9％ (n =4385 )groups.Multivariate Cox regression analysis was performed to determine whether RDW is an independent risk factor of all-cause mortality in overall patients,patients with various etiologies.Multivariate Cox proportional hazard analysis was performed to determine the risk of all-cause mortality among various RDW groups.Results ( 1 ) Compared with RDW ≤ 13.2％ group,adjusted hazard ratios (HRs) and 95％ confidence intervals (CIs) of all-cause mortality for RDW 13.3％ -14.1％,14.2％ -14.8％ and ≥ 14.9％ were 0.892 (95 ％ CI 0.818-0.973,P =0.01 ),0.859 (95 ％ CI 0.793 -0.931,P ＜0.01) and 1.034 (95％ CI 0.961 - 1.111,P =0.373) respectively. (2) Compared with MCV normal group,the adjusted HRs of MCV elevation and MCV decline groups were 1.351 (95％ CI 1.063 - 1.718,P ＜0.01 ) and 1.316 (95％ CI 1.034 - 1.675,P ＜ 0.01 ),respectively.(3) Compared to patients with rheumatic heart diseases,the adjusted HR for all-cause mortality in patients with coronary heart disease,dilated cardiomyopathy and hypertensive heart disease with RDW ＞ 16％ were 1.437 (95％ CI 1.141 -1.810,P＜0.01),1.651 (95％ CI 1.276 -2.138,P＜0.01) and 1.276 (95％ CI 1.004- 1.621,P ＜ 0.01 ),respectively.(4) The RDW is independently correlated with BMI ( r =- 0.345,P ＜ 0.01 ),diastolic blood pressure( r =- 0.321,P ＜ 0.01 ),albumin ( r =- 0.411,P ＜ 0.01 ),blood urine nitrogen ( r =0.476,P ＜ 0.01 ),right ventricular end-diastolic diameter( r =0.383,P ＜ 0.01 ),LVEF ( r =- 0.463,P ＜0.01 ) and heart rate( r =0.379,P ＜0.01 ).Conclusions There is a J shape relationship between allcause mortality and RDW.The elevation or decline of MCV with increased RDW is hnked with increased allcause mortality in CHF patients.

Objective To determinate the prognostic value of etiology in patients with chronic systolic heart failure (CSHF).Methods Data of in-hospital patients with CSHF were investigated between 2000 and 2010 from 12 hospitals in Hubei province.All patients were followed up through telephone calls.Univariate and multivariate Cox proportional hazards analyses were then used to explore the differences in the all-cause mortality,heart failure (HF) mortality and sudden cardiac death (SCD) among patients caused by different etiologies.Kaplan-Meier curve were then constructed and Univariate and multivariate Cox regression analyses were used to select demographic and clinical variables in predicting the all-cause mortality,HF mortality and SCD in CSHF patients.Multivariate logistic models and ROC curve were developed with or without the cinfirmed etiology to assess the incremental additive information related to different etiologies.Results (1)Over the median 3 (2-4) years follow-up program,6453 (38.69％) patients died,including 5505 (33.00％) due to HF prognosis and 717 (4.30％) died of SCD.All-cause mortality rates accounted for 34.50％,54.30％,41.48％ and 15.76％,with HF mortality rates as 30.11％,44.95％,36.25％ and 13.10％.SCDs accounted 8.46％,8.45％,9.84％ and 1.05％ in patients with CHD,DCM,HHD and RHD,respectively.(2) Compared with RHD patients,the adjusted HRs for all-cause mortality were 1.554 (1.240 to 1.947;P＜0.001),1.405(1.119 to 1.764;P=0.003) and 1.315(1.147 to 1.467;P=0.005) while the adjusted HRs and 95％CIs for HF mortality were 1.458( 1.213-1.751 ;P＜0.001 ),1.763( 1.448-2.147;P＜0.001 ) and 1.281 ( 1.067-1.537; P=0.008),in patients with CHD,DCM and HHD,respectively.There were no significant differences in CHD (HR 3.345; 95％ CI,1.291 to 8.666; P=0.013 ) or HHD (HR 2.062; 95％CI,0.794 to 5.352; P=0.137 ),while only DCM ( HR 4.764; 95％CI,1.799 to 12.618;P=0.002) remained significant in SCD despite of the multivariate adjustment.(3) Etiology increased the sensitivity and specificity of predicting models for all-cause mortality(AUC 0.839,95％CI,0.832to 0.845 vs.0.776,95％CI,0.768 to 0.784) and HF mortality(AUC 0.814,95％CI,0.806 to 0.822 vs.0.796,95％CI,0.788 to 0.804) but not with SCD (AUC 0.777,95％CI,0.749 to 0.809 vs.0.747,95％CI,0.727 to 0.766).Conclusion CSHF due to CHD,DCM and HHD carried a worse prognosis than that of RHD.Different etiologies provided significant incremental prognostic information beyond readily available clinical variables for all-cause mortality and HF mortality.

Objective To evaluate the current status of chronic heart failure (CHF) in Hubei province and analyze the epidemiology of CHF including the general condition, etiology and pharmacological therapy.Methods Data of in-hospital patients with CHF were investigated between 2000 and 2010 from 12 hospitals in Hubei Province. Inclusion criteria: over 18 years of age, organic heart disease and with the symptom of HF including dyspnea and fatigue. Patients with a history of myocardial infarction in the prior 12 months,congenital heart disease, pericardial disease and the history of cancer were excluded. Results (1) A total of 12 450 patients were enrolled (7166 male, 57.56%). The average age was (62.0±14.5) years. Patients in the scale of age ≥80, 70-79, 60-69, 50-59, 40-49 and ＜40 was 9.53%(1187/12 450), 30.80% (3835/12 450), 23.45% (2920/12 450), 18.81% (2342/12 450), 10.73% (1336/12 450) and 6.67% (830/12 450), respectively (P<0.01). The NYHA class Ⅰ,Ⅱ,Ⅲ and Ⅳ was 0.60%, 23.20%, 50.31% and 26.50%, respectively. (2) The age of patients was significant reduced from 2000-2003, 2004-2006 to 2007-2010 [(66.4±14.1) years, (64.9±14.4) years and (64.2±14.8) years, P<0.01]. (3) The major causes of CHF were hypertension (31.54%), coronary heart disease (28.24%), dilated cardiomyopathy (26.57%) and rheumatic valvular heart disease (17.49%). The most frequent etiology for CHF was rheumatic valvular heart disease in patients aged less than 40 years old, dilated cardiomyopathy in patients aged 40-49 and 50-59 years and hypertension in patients aged 60-69, 70-79 and ≥80 years. (4) Drug use was as follows: Digitalis (47.49%), diuretics (68.75%), ACEI (50.66%),β-blocker (44.06%) and aldosterone antagonist (53.08%). Use of digitalis (Wald χ2=903.41, P<0.01;r=0.271,P<0.01), diuretics (Wald χ2=818.05, P<0.01;r=0.249, P<0.01), aldosterone antagonists (Wald χ2=76.92, P<0.01;r=0.091, P<0.01) increased while the β-blocker (Wald χ2=160.65, P<0.01;r=-0.117,P<0.01) declined in proportion to NYHA class increase.Conclusions The age of in-hospital patients with CHF declined in the previous 10 years. The primary etiology was hypertension for aged CHF in-hospital patients with CHF. There was big gap between guideline recommended standard therapy and current drug use for in-hospital patients with CHF in Hubei province.