OBJECTIVE: To evaluate the efficacy and safety of Shexiang Tongxin Dropping Pill (STDP) in treating stable angina patients with phlegm-heat and blood-stasis syndrome by exercise duration and metabolic equivalents. METHODS: This multicenter, randomized, double-blind, placebo-controlled clinical trial enrolled stable angina patients with phlegm-heat and blood-stasis syndrome from 22 hospitals. They were randomized 1:1 to STDP (35 mg/pill, 6 pills per day) or placebo for 56 days. The primary outcome was the exercise duration and metabolic equivalents (METs) assessed by the standard Bruce exercise treadmill test after 56 days of treatment. The secondary outcomes included the total angina symptom score, Chinese medicine (CM) symptom scores, Seattle Angina Questionnaire (SAQ) scores, changes in ST-T on electrocardiogram and adverse events (AEs). RESULTS: This trial enrolled 309 patients, including 155 and 154 in the STDP and placebo groups, respectively. STDP significantly prolonged exercise duration with an increase of 51.0 s, compared to a decrease of 12.0 s with placebo (change rate: -11.1% vs. 3.2%, P<0.01). The increase in METs was significantly greater in the STDP group than in the placebo group (change: -0.4 vs. 0.0, change rate: -5.0% vs. 0.0%, P<0.01). The improvement of total angina symptom scores (25.0% vs. 0.0%), CM symptom scores (38.7% vs. 11.8%), reduction of nitroglycerin consumption (100.0% vs. 11.3%), and all domains of SAQ, were significantly greater with STDP than placebo (all P<0.01). The changes in Q-T intervals at 28 and 56 days from baseline were similar between the two groups (both P>0.05). Twenty-five participants (16.3%) with STDP and 16 (10.5%) with placebo experienced AEs (P=0.131), with no serious AEs observed. CONCLUSION STDP could improve exercise tolerance in patients with stable angina and phlegm-heat and blood stasis syndrome, with a favorable safety profile. (Registration No. ChiCTR-IPR-15006020).
Humans ; Double-Blind Method ; Drugs, Chinese Herbal/adverse effects* ; Male ; Female ; Middle Aged ; Angina, Stable/physiopathology* ; Aged ; Syndrome ; Treatment Outcome ; Placebos ; Tablets

Objective To analyze the risk factors and survival status of Epstein-Barr virus(EBV)infection in pa-tients with aplastic anemia(AA)after haploid allogeneic hematopoietic stem cell transplantation(Haplo-HSCT).Methods Clinical data of 78 AA patients who underwent Haplo-HSCT in the hematology department of a hospital from January 1,2019 to October 31,2022 were analyzed retrospectively.The occurrence and onset time of EBV viremia,EBV-related diseases(EBV diseases),and post-transplant lymphoproliferative disorders(PTLD)were ob-served,risk factors and survival status were analyzed.Results Among the 78 patients,38 were males and 40 were females,with a median age of 33(9-56)years old;53 patients experienced EBV reactivation,with a total inci-dence of 67.9％,and the median time for EBV reactivation was 33(13,416)days after transplantation.Among pa-tients with EBV reactivation,49 cases(62.8％)were simple EBV viremia,2 cases(2.6％)were possible EBV di-seases,and 2 cases(2.6％)were already confirmed EBV diseases(PTLD).Univariate analysis showed that age 1＜40 years old at the time of transplantation,umbilical cord blood infusion,occurrence of acute graft-versus-host disease(aGVHD)after transplantation,and concurrent cytomegalovirus(CMV)infection were independent risk fac-tors for EBV reactivation in AA patients after Haplo-HSCT.Multivariate analysis showed that concurrent CMV in-fection was an independent risk factor for EBV reactivation in A A patients after Haplo-HSCT(P=0.048).Ritu-ximab intervention before stem cell reinfusion was a factor affecting the duration of EBV reactivation(P＜0.05).The mortality of EBV viremia,EBV diseases,and PTLD alone were 8.2％,50.0％,and 100％,respectively.The 2-year overall survival rate of patients with and without EBV reactivation were 85.3％,and 90.7％,respectively,difference was not statistically significant(P=0.897).However,patients treated with rituximab had 2-year lower survival rate than those who did not use it,with a statistically significant difference(P=0.046).Conclusion EBV reactivation is one of the serious complications in AA patients after Haplo-HSCT,which affects the prognosis and survival of patients.

Objective To investigate the risk factors for delayed union of extra-articular fractures of the middle and lower third of the tibia treated by locking plate.Methods Total of 135 patients of extra-articular fractures of the middle and lower third of the tibia from January 2013 to December 2018 were retrospectively analyzed,including 85 males and 50 females,ranged from 19 to 80 years old.All cases were treated with locking plates.The patients were divided into union group and delayed union group ac-cording to the condition of fracture union.The risk factors of delayed healing were determined by univariate analysis of 14 factors that might affect fracture healing first,then the factors with significance were analyzed by binary Logistic regression.Results There were 13 patients of delayed union,and the rate of delayed union was 9.63％.Univariate analysis showed that delayed union was associated with age,smoking,reduction method,anemia and time of preoperative preparation.Regression analysis showed thatage[OR=0.849,95％CI(0.755,0.954),P=0.006],smoking[OR=0.020,95％CI(0.002,0.193),P=0.001],reduction method[OR=23.924,95％CI(2.210,258.943),P=0.009],anemia[OR=0.016,95％CI(0.001,0.289),P=0.005]were the con-tributory factors for delayed union.Conclusion Young age,smoking,closed reduction and anemia are the risk factors for de-layed union of extra-articular fractures of the middle and lower third of the tibia treated by locking plate.

Given the dual role of autophagy presenting in tumorigenesis and inhibition, we established an autophagy-related gene prognostic index (ARGPI) with validation to well predict the biochemical recurrence (BCR), metastasis, as well as chemoresistance for patients with prostate cancer (PCa) who underwent radical radiotherapy or prostatectomy. Then, Lasso and COX regression was used to develop the ARGPI. We performed the whole analyses through R packages (version 3.6.3). Secreted phosphoprotein 1 (SPP1), single-minded 2 (SIM2), serine protease inhibitor b5 (SERPINB5), aldehyde dehydrogenase 2 (ALDH2), and acyl-CoA synthetase long-chain 3 (ACSL3) were eventually used to establish the ARGPI score. Patients were divided into two different-risk groups based on the median ARGPI score, high-risk patients with a higher risk of BCR than low-risk patients (hazard ratio [HR]: 5.46, 95% confidence interval [CI]: 3.23-9.24). The risk of metastasis of high-risk patients was higher than low-risk patients (HR: 11.31, 95% CI: 4.89-26.12). In The Cancer Genome Atlas (TCGA) dataset, we observed similar prognostic value of ARGPI in terms of BCR-free survival (HR: 1.79, 95% CI: 1.07-2.99) and metastasis-free survival (HR: 1.80, 95% CI: 1.16-2.78). ARGPI score showed a diagnostic accuracy of 0.703 for drug resistance. Analysis of gene set enrichment analysis (GSEA) indicated that patients in the high-risk group were significantly positively related to interleukin (IL)-18 signaling pathway. Moreover, ARGPI score was significantly related to cancer-related fibroblasts (CAFs; r = 0.36), macrophages (r = 0.28), stromal score (r = 0.38), immune score (r = 0.35), estimate score (r = 0.39), as well as tumor purity (r = -0.39; all P < 0.05). Drug analysis showed that PI-103 was the common sensitive drug and cell line analysis indicated that PC3 was the common cell line of PI-103 and the definitive gene. In conclusion, we found that ARGPI could predict BCR, metastasis, and chemoresistance in PCa patients who underwent radical radiotherapy or prostatectomy.
Male ; Humans ; Prognosis ; Neoplasm Recurrence, Local/pathology* ; Prostatic Neoplasms/pathology* ; Prostatectomy ; Drug Resistance ; Aldehyde Dehydrogenase, Mitochondrial

Objective: To study the incidence of bloodstream infections, pathogen distribution, and antibiotic resistance profile in patients with hematological malignancies. Methods: From January 2018 to December 2021, we retrospectively analyzed the clinical characteristics, pathogen distribution, and antibiotic resistance profiles of patients with malignant hematological diseases and bloodstream infections in the Department of Hematology, Nanfang Hospital, Southern Medical University. Results: A total of 582 incidences of bloodstream infections occurred in 22,717 inpatients. From 2018 to 2021, the incidence rates of bloodstream infections were 2.79%, 2.99%, 2.79%, and 2.02%, respectively. Five hundred ninety-nine types of bacteria were recovered from blood cultures, with 487 (81.3%) gram-negative bacteria, such as Klebsiella pneumonia, Escherichia coli, and Pseudomonas aeruginosa. Eighty-one (13.5%) were gram-positive bacteria, primarily Staphylococcus aureus, Staphylococcus epidermidis, and Enterococcus faecium, whereas the remaining 31 (5.2%) were fungi. Enterobacteriaceae resistance to carbapenems, piperacillin/tazobactam, cefoperazone sodium/sulbactam, and tigecycline were 11.0%, 15.3%, 15.4%, and 3.3%, with a descending trend year on year. Non-fermenters tolerated piperacillin/tazobactam, cefoperazone sodium/sulbactam, and quinolones at 29.6%, 13.3%, and 21.7%, respectively. However, only two gram-positive bacteria isolates were shown to be resistant to glycopeptide antibiotics. Conclusions: Bloodstream pathogens in hematological malignancies were broadly dispersed, most of which were gram-negative bacteria. Antibiotic resistance rates vary greatly between species. Our research serves as a valuable resource for the selection of empirical antibiotics.
Humans ; Bacteremia/epidemiology* ; Cefoperazone ; Sulbactam ; Retrospective Studies ; Drug Resistance, Bacterial ; Microbial Sensitivity Tests ; Hematologic Neoplasms ; Sepsis ; Anti-Bacterial Agents/pharmacology* ; Gram-Negative Bacteria ; Gram-Positive Bacteria ; Piperacillin, Tazobactam Drug Combination ; Escherichia coli

Objectives: To investigated the safety and efficacy of treating patients with acute non-ST-segment elevation myocardial infarction (NSTEMI) and elevated levels of N-terminal pro-hormone B-type natriuretic peptide (NT-proBNP) with levosimendan within 24 hours of first medical contact (FMC). Methods: This multicenter, open-label, block-randomized controlled trial (NCT03189901) investigated the safety and efficacy of levosimendan as an early management strategy of acute heart failure (EMS-AHF) for patients with NSTEMI and high NT-proBNP levels. This study included 255 patients with NSTEMI and elevated NT-proBNP levels, including 142 males and 113 females with a median age of 65 (58-70) years, and were admitted in the emergency or outpatient departments at 14 medical centers in China between October 2017 and October 2021. The patients were randomly divided into a levosimendan group (n=129) and a control group (n=126). The primary outcome measure was NT-proBNP levels on day 3 of treatment and changes in the NT-proBNP levels from baseline on day 5 after randomization. The secondary outcome measures included the proportion of patients with more than 30% reduction in NT-proBNP levels from baseline, major adverse cardiovascular events (MACE) during hospitalization and at 6 months after hospitalization, safety during the treatment, and health economics indices. The measurement data parameters between groups were compared using the t-test or the non-parametric test. The count data parameters were compared between groups using the χ² test. Results: On day 3, the NT-proBNP levels in the levosimendan group were lower than the control group but were statistically insignificant [866 (455, 1 960) vs. 1 118 (459, 2 417) ng/L, Z=-1.25,P=0.21]. However, on day 5, changes in the NT-proBNP levels from baseline in the levosimendan group were significantly higher than the control group [67.6% (33.8%,82.5%)vs.54.8% (7.3%,77.9%), Z=-2.14, P=0.03]. There were no significant differences in the proportion of patients with more than 30% reduction in the NT-proBNP levels on day 5 between the levosimendan and the control groups [77.5% (100/129) vs. 69.0% (87/126), χ²=2.34, P=0.13]. Furthermore, incidences of MACE did not show any significant differences between the two groups during hospitalization [4.7% (6/129) vs. 7.1% (9/126), χ²=0.72, P=0.40] and at 6 months [14.7% (19/129) vs. 12.7% (16/126), χ²=0.22, P=0.64]. Four cardiac deaths were reported in the control group during hospitalization [0 (0/129) vs. 3.2% (4/126), P=0.06]. However, 6-month survival rates were comparable between the two groups (log-rank test, P=0.18). Moreover, adverse events or serious adverse events such as shock, ventricular fibrillation, and ventricular tachycardia were not reported in both the groups during levosimendan treatment (days 0-1). The total cost of hospitalization [34 591.00(15 527.46,59 324.80) vs. 37 144.65(16 066.90,63 919.00)yuan, Z=-0.26, P=0.80] and the total length of hospitalization [9 (8, 12) vs. 10 (7, 13) days, Z=0.72, P=0.72] were lower for patients in the levosimendan group compared to those in the control group, but did not show statistically significant differences. Conclusions: Early administration of levosimendan reduced NT-proBNP levels in NSTEMI patients with elevated NT-proBNP and did not increase the total cost and length of hospitalization, but did not significantly improve MACE during hospitalization or at 6 months.
Male ; Female ; Humans ; Aged ; Natriuretic Peptide, Brain ; Simendan/therapeutic use* ; Non-ST Elevated Myocardial Infarction ; Heart Failure/drug therapy* ; Peptide Fragments ; Arrhythmias, Cardiac ; Biomarkers ; Prognosis

This study aims to investigate the effect of Chaihu Shugan Powder(CHSG) on liver injury in rats with intrahepatic cholestasis by regulating farnesoid X receptor(FXR)/nuclear factor erythroid-2-related factor(Nrf2)/antioxidant response element(ARE) pathway. Eighty-four SD rats were classified into normal group, model group, CHSG-L group(0.5 g·kg~(-1)), CHSG-H group(2.5 g·kg~(-1)), ursodeoxycholic acid group(UDCA group, 100 mg·kg~(-1)), CHSG-H+sh-NC group(2.5 g·kg~(-1) CHSG+subcutaneous injection of sh-NC lentivirus), CHSG-H+sh-FXR group(2.5 g·kg~(-1) CHSG+subcutaneous injection of sh-FXR lentivirus), with 12 rats in each group. Rats were treated with corresponding drugs except for the normal group and the model group, once a day, for 7 days. On 5 th day, rats, except the normal group, were given α-naphthalene isothiocyanate(ANIT) at a dose of 100 mg·kg~(-1), once a day for 3 days to induce intrahepatic cholestasis, and the normal group was given the same amount of normal saline. Rats were anesthetized 1 h after the last administration and the 2 h bile flow was measured. Aeroset chemistry analyzer was employed to detect the levels of alanine aminotransferase(ALT), aspartate aminotransferase(AST), total bilirubin(TBIL), and total bile acid(TBA) in rat serum. Based on hematoxylin and eosin(HE) staining, the pathological changes of rat liver tissue were observed. Glutathione peroxidase(GSH-Px), superoxide dismutase(SOD), and malondialdehyde(MDA) in rat liver tissue homogenate were monitored with corresponding kits. Western blot was used to detect the expression of FXR, Nrf2, and heme oxygenase-1(HO-1) proteins in rat liver tissue. Compared with the normal group, the model group showed many spots or concentrated necrotic areas in the liver tissue, infiltration of a large number of inflammatory cells, swelling liver cells with nuclear shrinkage. The 2 h bile flow, levels of GSH-Px and SOD, and relative expression of FXR, Nrf2, and HO-1 proteins were significantly lower, and the levels of ALT, AST, TBIL, TBA and MDA were significantly higher in the model group than in the normal group. Compared with the model group, CHSG-L group, CHSG-H group, and UDCA group demonstrated significant alleviation of pathological damage of the liver tissue, significantly high 2 h bile flow, levels of GSH-Px and SOD, and expression of FXR, Nrf2 and HO-1 proteins, and significantly low levels of ALT, AST, TBIL, TBA and MDA. Compared with the CHSG-H group, the CHSG-H+sh-FXR group had worse liver pathological damage, significantly low levels of 2 h bile flow, levels of GSH-Px and SOD, and expression of FXR, Nrf2, and HO-1 proteins, and significantly high levels of ALT, AST, TBIL, TBA, and MDA. CHSG may protect against liver injury in rats with intrahepatic cholestasis by activating the FXR/Nrf2/ARE pathway.
Rats ; Animals ; 1-Naphthylisothiocyanate/toxicity* ; Powders ; NF-E2-Related Factor 2/genetics* ; Rats, Sprague-Dawley ; Cholestasis, Intrahepatic/drug therapy* ; Liver ; Superoxide Dismutase ; Oxidative Stress

Objective: To investigate the effectiveness of nucleos(t)ide analogues in the treatment of HBeAg-positive chronic hepatitis B with normal alanine aminotransferase and high level of HBV DNA. Methods: Treatment-naïve chronic hepatitis B patients who were followed up at the Center of Infectious Diseases, West China Hospital of Sichuan University from January 2019 to January 2020 were selected as subjects. Demographic characteristics, the results of laboratory examination before treatment and one year after treatment were retrospectively collected. Patients were divided into tenofovir dipivoxil (TDF) and propofol fumurate tenofovir (TAF) treatment group according to different types of medication. The changes of serum HBV DNA level, HBeAg serological conversion and HBsAg quantitative level were analyzed and compared between the two groups. Results: A total of 38 cases were enrolled. Among them, there were 16 and 22 cases in the TDF and TAF group, respectively. There was no statistically significant difference in demographic characteristics, baseline HBV DNA levels and HBsAg quantitative levels between the two groups. Virological response was achieved in 60.5% (23/38) of patients after one year of antiviral therapy. Serum HBV DNA levels below the lower limit of detection [68.2% (15/22) vs. 50.0% (8/16), P=0.258] and higher HBeAg seroconversion rate [18.2%] (4/22) vs. 6.3% (1/16), P=0.374] was obtained in TAF than TDF group; however, there was no statistically significant differences between the two. Serum HBsAg quantitative level was significantly reduced with TDF and TAF treatment. In addition, alanine aminotransferase elevation was reduced in TAF than TDF treated group. Multivariate logistic regression analysis showed that patient age was an independent predictor of a virological response to antiviral therapy. Conclusion: HBeAg-positive CHB patients with normal alanine aminotransferase, and high HBV DNA level can obtain better curative effect after TDF and TAF treatment.
Alanine Transaminase ; Antiviral Agents/therapeutic use* ; DNA, Viral ; Hepatitis B Surface Antigens ; Hepatitis B e Antigens ; Hepatitis B virus/genetics* ; Hepatitis B, Chronic ; Humans ; Retrospective Studies ; Tenofovir/therapeutic use* ; Treatment Outcome

Objective: To investigate the functional outcomes and postoperative complications of Cheng's GIRAFFE reconstruction after proximal gastrectomy. Methods: A descriptive case series study was conducted. Clinical data of 100 patients with adenocarcinoma of the esophagogastric junction who underwent Cheng's GIRAFFE reconstruction after proximal gastrectomy in Cancer Hospital of University of Chinese Academy of Sciences (64 cases), Zhejiang Provincial Hospital of Chinese Medicine (24 cases), Lishui Central Hospital (10 cases), Huzhou Central Hospital (1 case) and Ningbo Lihuili Hospital (1 case) from September 2017 to June 2021 were retrospectively analyzed. Of 100 patients, 64 were males and 36 were females; the mean age was (61.3 ± 11.1) years and the BMI was (22.7±11.1) kg/m(2). For TNM stage, 68 patients were stage IA, 24 were stage IIA and 8 were stage IIB. Postoperative functional results and postoperative complications of radical gastrectomy with Giraffe reconstruction were analyzed and summarized. Gastroesophageal reflux disease questionnaire (RDQ) score and postoperative endoscopy were used to evaluate the occurrence of reflux esophagitis and its grade (grade N, grade A, grade B, grade C, and grade D from mild to severe reflux). The continuous data conforming to normal distribution were expressed as (mean ± standard deviation), and those with skewed distribution were presented as median (Q1, Q3). Results: All the 100 patients successfully completed R0 resection, including 77 patients undergoing laparoscopic surgery and 23 patients undergoing laparotomy. The Giraffe anastomosis time was (38.6±14.0) min; the blood loss was (73.0±18.4) ml; the postoperative hospital stay was 9.5 (8.2, 13.0) d; the hospitalization cost was (6.0±0.3) ten thousand yuan. Fourteen cases developed perioperative complications (14.0%), including 7 cases of pleural effusion or pneumonia, 3 cases of anastomotic leakage, 2 cases of gastric emptying disorder, 1 case of gastrointestinal hemorrhage and 1 case of anastomotic stenosis, who were all improved and discharged after symptomatic management. Patients were followed up for (33.3±1.6) months. Eight patients were found to have reflux symptoms by RDQ scale six months after surgery, and 11 patients (11/100,11.0%) were found to have reflux esophagitis by gastroscopy, including 6 in grade A, 3 in grade B, and 2 in grade C. All the patients could control their reflux symptoms with behavioral guidance or oral PPIs. Conclusion: Cheng's GIRAFFE reconstruction has good anti-reflux efficacy and gastric emptying function; it can be one of the choices of reconstruction methods after proximal gastrectomy.
Adenocarcinoma/surgery* ; Aged ; Esophageal Neoplasms/surgery* ; Esophagitis, Peptic/etiology* ; Esophagogastric Junction/surgery* ; Female ; Gastrectomy/methods* ; Gastroesophageal Reflux/etiology* ; Humans ; Laparoscopy ; Male ; Middle Aged ; Reconstructive Surgical Procedures/methods* ; Recovery of Function ; Retrospective Studies ; Stomach Neoplasms/surgery*

Tongsaimai Tablets/Capsules are composed of Lonicerae Japonicae Flos, Angelicae Sinensis Radix, Achyranthis Bidentatae Radix, Codonopsis Radix, Dendrobii Caulis, Astragali Radix, Scrophulariae Radix, and Glycyrrhizae Radix et Rhizoma, and are effective in promoting blood circulation, removing blood stasis, supplementing Qi, and nourishing Yin. It is widely used in the treatment of peripheral vascular diseases. With 40 years of clinical application, it has accumulated substantial research data and application experience. Its good clinical efficacy and pharmacoeconomic benefits in improving the clinical symptoms of peripheral vascular diseases have been confirmed by relevant research. Meanwhile, this drug has also been recommended by many expert consensus, guidelines, and teaching materials, serving as one of the most commonly used Chinese patent medicines in clinical practice. To further improve the understanding of the drug among clinicians and properly guide its clinical medication, the China Association of Chinese Medicine took the lead and organized experts to jointly formulate this expert consensus. Based on the questionnaire survey of clinicians and the systematic review of research literature on Tongsaimai Tablets/Capsules with clinical problems in the PICO framework, the consensus, combined with expert experience, concludes recommendations or consensus suggestions by GRADE system with the optimal evidence available through the nominal group technique. This consensus defines the indications, usage, dosage, course of treatment, medication time, combined medication, and precautions of Tongsaimai Tablets/Capsules in the treatment of peripheral vascular diseases, and explains the safety of its clinical application. It is recommended for clinicians and pharmacists in the peripheral vascular department(vascular surgery), traditional Chinese medicine surgery(general surgery), and endocrinology department of hospitals at all levels in China.
Capsules ; Consensus ; Drugs, Chinese Herbal ; Humans ; Medicine, Chinese Traditional ; Peripheral Vascular Diseases ; Tablets