Aim To investigate the effects of Cartham-us tinctorius L.extract(CTLE)on oxidative stress,lipid metabolism,and apoptosis levels of mice with al-cohol-induced liver injury and its mechanism of action.Methods The mouse model of alcohol-associated liver disease was established by chronic alcohol feeding and acute alcohol gavage.Mice were randomly divided into four groups.During the modeling period,the state changes of mice were observed every day,and their weight was recorded.At the end of modeling,blood and liver tissues were collected from each group of mice.The blood of mice was analyzed biochemically,and HE staining and Oil Red O staining were used to evaluate further the degree of pathological damage in the liver of mice.Quantitative real-time PCR(qPCR)and Western blot were applied to detect the mRNA and protein expression levels of p-PI3K,PI3K,p-Akt,Akt,p-mTOR,mTOR,p-FoxO1,FoxO1,p-FoxO3a,FoxO3a,p-FoxO4,FoxO4,BCL and BAX factors.Results Compared to the model group,the CTLE administration group showed improved hepatic patho-logical injury and reduced lipid deposition.The bio-chemical indexes in serum and liver,such as ALT,AST,TG,TC,and MDA levels were reduced,while GSH and SOD levels increased.Regulating the PI3K/Akt/FoxO pathway resulted in increased production of SOD,which reduced damage and apoptosis caused by reactive oxygen species(ROS).Conclusions CTLE can exert anti-oxidative stress and anti-apoptotic effects through the PI3K/Akt/FoxO pathway and attenuates alcoholic liver injury in mice,providing new ideas for the treatment of alcoholic liver disease and the develop-ment of related drugs.

Objective To analyze the genetic subtypes of human immunodeficiency virus (HIV) and the prevalence of pretreatment drug resistance in the newly reported HIV-infected men in Guangxi. Methods The stratified random sampling method was employed to select the newly reported HIV-infected men aged≥50 years old in 14 cities of Guangxi from January to June in 2020.The pol gene of HIV-1 was amplified by nested reverse transcription polymerase chain reaction and then sequenced.The mutation sites associated with drug resistance and the degree of drug resistance were then analyzed. Results A total of 615 HIV-infected men were included in the study.The genetic subtypes of CRF01_AE,CRF07_BC,and CRF08_BC accounted for 57.4% (353/615),17.1% (105/615),and 22.4% (138/615),respectively.The mutations associated with the resistance to nucleoside reverse transcriptase inhibitors (NRTI),non-nucleoside reverse transcriptase inhibitors (NNRTI),and protease inhibitors occurred in 8 (1.3%),18 (2.9%),and 0 patients,respectively.M184V (0.7%) and K103N (1.8%) were the mutations with the highest occurrence rates for the resistance to NRTIs and NNRTIs,respectively.Twenty-two (3.6%) patients were resistant to at least one type of inhibitors.Specifically,4 (0.7%),14 (2.3%),4 (0.7%),and 0 patients were resistant to NRTIs,NNRTIs,both NRTIs and NNRTIs,and protease inhibitors,respectively.The pretreatment resistance to NNRTIs had much higher frequency than that to NRTIs (2.9% vs.1.3%;χ²=3.929,P=0.047).The prevalence of pretreatment resistance to lamivudine,zidovudine,tenofovir,abacavir,rilpivirine,efavirenz,nevirapine,and lopinavir/ritonavir was 0.8%, 0.3%, 0.7%, 1.0%, 1.3%, 2.8%, 2.9%, and 0, respectively. Conclusions CRF01_AE,CRF07_BC,and CRF08_BC are the three major strains of HIV-infected men≥50 years old newly reported in Guangxi,2020,and the pretreatment drug resistance demonstrates low prevalence.
Male ; Humans ; Middle Aged ; Reverse Transcriptase Inhibitors/therapeutic use* ; HIV Infections/drug therapy* ; Drug Resistance, Viral/genetics* ; China/epidemiology* ; Mutation ; HIV-1/genetics* ; Protease Inhibitors/therapeutic use* ; Genotype

Objective: To compare the predictive efficacy of the two thrombosis risk assessment scores (Padua and IMPEDE scores) in venous thromboembolism (VTE) within 6 months in patients with newly diagnosed multiple myeloma (NDMM) in China. Methods: This study reviewed the clinical data of 421 patients with NDMM hospitalized in Beijing Jishuitan Hospital from April 2014 to February 2022. The sensitivity, specificity, accuracy, and Youden index of the two scores were calculated to quantify the thrombus risk assessment of VTE by the Padua and IMPEDE scores. The receiver operating characteristics curves of the two evaluation scores were drawn. Results: The incidence of VTE was 14.73%. The sensitivity, specificity, accuracy, and Youden index of the Padua score were 100%, 0%, 14.7%, and 0% and that of the IMPEDE score was 79%, 44%, 49.2%, and 23%, respectively. The areas under the curve of Padua and IMPEDE risk assessment scores were 0.591 and 0.722, respectively. Conclusion: IMPEDE score is suitable for predicting VTE within 6 months in patients with NDMM.
Humans ; Venous Thromboembolism/etiology* ; Multiple Myeloma/diagnosis* ; Risk Assessment ; Risk Factors ; ROC Curve ; Retrospective Studies

Objective: To explore the value of cardiac magnetic resonance imaging (CMR) in the risk stratification of hypertrophic cardiomyopathy (HCM). Methods: HCM patients who underwent CMR examination in Fuwai Hospital between March 2012 and May 2013 were retrospectively enrolled. Baseline clinical and CMR data were collected and patient follow-up was performed using telephone contact and medical record. The primary composite endpoint was sudden cardiac death (SCD) or and equivalent event. The secondary composite endpoint was all-cause death and heart transplant. Patients were divided into SCD and non-SCD groups. Cox regression was used to explore risk factors of adverse events. Receiver operating characteristic (ROC) curve analysis was used to assess the performance and the optimal cut-off of late gadolinium enhancement percentage (LGE%) for the prediction of endpoints. Kaplan-Meier and log-rank tests were used to compare survival differences between groups. Results: A total of 442 patients were enrolled. Mean age was (48.5±12.4) years and 143(32.4%) were female. At (7.6±2.5) years of follow-up, 30 (6.8%) patients met the primary endpoint including 23 SCD and 7 SCD equivalent events, and 36 (8.1%) patients met the secondary endpoint including 33 all-cause death and 3 heart transplant. In multivariate Cox regression, syncope(HR=4.531, 95%CI 2.033-10.099, P<0.001), LGE% (HR=1.075, 95%CI 1.032-1.120, P=0.001) and left ventricular ejection fraction (LVEF) (HR=0.956, 95%CI 0.923-0.991, P=0.013) were independent risk factors for primary endpoint; Age (HR=1.032, 95%CI 1.001-1.064, P=0.046), atrial fibrillation (HR=2.977, 95%CI 1.446-6.131, P=0.003),LGE% (HR=1.075, 95%CI 1.035-1.116, P<0.001) and LVEF (HR=0.968, 95%CI 0.937-1.000, P=0.047) were independent risk factors for secondary endpoint. ROC curve showed the optimal LGE% cut-offs were 5.1% and 5.8% for the prediction of primary and secondary endpoint, respectively. Patients were further divided into LGE%=0, 0P<0.001) and the accumulated incidence of primary endpoint was 1.2% (2/161), 2.2% (2/89), 10.5% (16/152) and 25.0% (10/40), respectively. Conclusion: LGE is an independent risk factor for SCD events as well as all-cause death and heart transplant. LGE is of important value in the risk stratification in patients with HCM.
Humans ; Female ; Adult ; Middle Aged ; Male ; Contrast Media ; Retrospective Studies ; Stroke Volume ; Gadolinium ; Ventricular Function, Left ; Magnetic Resonance Imaging ; Cardiomyopathy, Hypertrophic/diagnostic imaging* ; Death, Sudden, Cardiac ; Risk Assessment

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

Long-segment lichen sclerosus (LS) urethral stricture is a challenge for urologists. Limited data are available for surgeons to make a surgical decision between Kulkarni and Asopa urethroplasty. In this retrospective study, we investigated the outcomes of these two procedures in patients with LS urethral stricture. Between January 2015 and December 2020, 77 patients with LS urethral stricture underwent Kulkarni and Asopa procedures for urethroplasty in the Department of Urology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine (Shanghai, China). Of the 77 patients, 42 (54.5%) underwent the Asopa procedure and 35 (45.5%) underwent the Kulkarni procedure. The overall complication rate was 34.2% in the Kulkarni group and 19.0% in the Asopa group, and no difference was observed ( P = 0.105). Among the complications, no statistical difference was observed in the incidence of urethral stricture recurrence ( P = 0.724) or glans dehiscence ( P = 0.246) except for postoperative meatus stenosis ( P = 0.020). However, the recurrence-free survival rate between the two procedures was significantly different ( P = 0.016). Cox survival analysis showed that antiplatelet/anticoagulant therapy use ( P = 0.020), diabetes ( P = 0.003), current/former smoking ( P = 0.019), coronary heart disease ( P < 0.001), and stricture length ( P = 0.028) may lead to a higher hazard ratio of complications. Even so, these two techniques can still provide acceptable results with their own advantages in the surgical treatment of LS urethral strictures. The surgical alternative should be considered comprehensively according to the patient characteristics and surgeon preferences. Moreover, our results showed that antiplatelet/anticoagulant therapy use, diabetes, coronary heart disease, current/former smoking, and stricture length may be contributing factors of complications. Therefore, patients with LS are advised to undergo early interventions for better therapeutic effects.
Male ; Humans ; Urethral Stricture/etiology* ; Retrospective Studies ; Constriction, Pathologic/surgery* ; Lichen Sclerosus et Atrophicus/surgery* ; Treatment Outcome ; Urologic Surgical Procedures, Male/methods* ; China ; Urethra/surgery* ; Postoperative Complications/etiology* ; Mouth Mucosa ; Diabetes Mellitus/etiology* ; Anticoagulants ; Coronary Disease

Humans ; Receptors, Chimeric Antigen ; Hematopoietic Stem Cell Transplantation ; Precursor T-Cell Lymphoblastic Leukemia-Lymphoma ; Immunotherapy, Adoptive ; Antigens, CD19

AIM: To investigate the safety of bioequivalence (BE) studies of orally inhaled drug products (OIDPs) conducted by Phase I clinical Research Center of our hospital. METHODS: The safety data were collected from 482 healthy subjects enrolled in 20 OIDPs BE studies in Wuxi People's hospital from 2017 to 2022. The difference of adverse events (AEs) between test preparation and reference preparation were compared, as well as the influence of gender, age, mechanism of drug action and device type on AE were analyzed. RESULTS: A total of 102 cases of AEs were occurred in 77 subjects (16.0%, 77/482), 87 cases of AEs were related to experimental drugs, all AEs were mild or moderate, and no serious adverse events occurred. There was no difference in the incidence of AE between test preparation and reference preparation. In addition, gender, age, mechanism of drug action and device type had no significant effects on AEs. CONCLUSION: In 20 bioequivalence studies of OIDPs, OIDPs were safe and well tolerated in healthy subjects after dosing, and safety features of generic OIDPs and original drug were basically similar.

AIM: To explore the reasons for screening failure of healthy subjects in clinical trials of orally inhaled drug products (OIDPs). METHODS: Screening data of 1 432 healthy subjects who participated in clinical trials of OIDPs were collected. The main reasons for the screening failure, gender differences in screening failure rate and the correlation between age and screening failure rate were summarized and analyzed. RESULTS: The screening failure rate was 72.4 % and increased with age. The failure rate was slightly higher in females than in males. Besides abnormal vital signs (17.3%), abnormal laboratory test results (16.5%) and withdrawal of consent (7.6%), poor venous condition (13.9%), positive for cigarette test results (12.6%) and failure in inhalation training (7.1%) were also the other three main reasons affecting the screening success rate. Abnormal vital signs and poor venous conditions were the primary screening failure reasons for males and females, respectively. CONCLUSION: The screening success rate could be improved by informing fully and communicating effectively, selecting young subjects with strong understanding abilities, and enhancing the training skills of investigators.

Objective:To synthesize the findings of qualitative research on the treatment experience of cancer patients receiving immune checkpoint inhibitors therapy to provide a basis for developing relevant health education strategies and other supportive care interventions.Methods:Qualitative research on the treatment experience of cancer patients receiving immune checkpoint inhibitors therapy, published by May 2022, were searched in English and Chinese databases, including Cochrane Library, PubMed, Embase, PsycINFO, CINAHL, Web of Science, CNKI, Wanfang, VIP, and CBM. The quality of the included studies was evaluated by Joanna Briggs Institute Critical Appraisal Tool for qualitative studies. The research results were summarized and Meta-synthesis using the pooled integration method.Results:A total of 13 articles were included and 62 findings were grouped into 12 new categories according to their similarities. These 12 categories resulted in 4 synthesized findings: life was affected, facing multiple decision scenarios, presence of some unmet needs and gaining positive experiences and personal growth.Conclusions:Although patients experience some positive experiences, a large proportion of them experience significant health distress. Healthcare professionals should develop targeted health education with supportive care strategies on the basis of a comprehensive assessment.