Objective: To explore the efficacy and safety of Venetoclax combined with multidrug chemotherapy in patients with relapsed or refractory early T-cell precursor acute lymphoblastic leukemia (R/R ETP-ALL) . Methods: This study retrospectively analyzed 15 patients with R/R ETP-ALL who received Venetoclax combined with multidrug chemotherapy from December 2018 to February 2022. Among them, eight cases were combined with demethylated drugs, four cases were combined with demethylated drugs and HAAG chemotherapy regimen, two cases were combined with demethylated drugs and CAG regimen, and one case was combined with Cladribine. Specific usage and dosage of Venetoclax: 100 mg on day 1, 200 mg on day 2, 400 mg on day 3-28, orally; when combined with azole antifungal drugs, dosage was reduced to 100 mg/d. Results: Fifteen patients (10 males and 5 females) with R/R ETP-ALL were treated with Venetoclax and multidrug chemotherapy with a median age of 35 (12-42) years old. Of 4 refractory and 11 relapsed patients, the efficacy was evaluated on the 21th day following combined chemotherapy: the overall response rate, the complete response (CR) rate, and the CR with incomplete hematological recovery (CRi) rate were 67.7% (10/15), 60.0% (9/15), and 6.7% (1/15), respectively. For the overall study population, the 12-month overall survival (OS) rate was 60.0%, and the median OS was 17.7 months. The disease-free survival (DFS) rate of all CR patients at 12 months was 60.0%, and the median DFS did not reach. About 14 patients had Ⅲ-Ⅳ hematological toxicity, but these adverse reactions were all controllable. No adverse reaction in the nervous system and tumor lysis syndrome occurred in this study, and no adverse reaction of organs above grade Ⅲ occurred. Conclusion: Venetoclax combined with multidrug chemotherapy may be a safe and promising treatment option for patients with R/R ETP-ALL.
Male ; Female ; Humans ; Adult ; Retrospective Studies ; Treatment Outcome ; Bridged Bicyclo Compounds, Heterocyclic/therapeutic use* ; Antineoplastic Combined Chemotherapy Protocols ; Precursor T-Cell Lymphoblastic Leukemia-Lymphoma/drug therapy* ; Precursor Cells, T-Lymphoid ; Leukemia, Myeloid, Acute/drug therapy*

Inductively coupled plasma mass spectrometry (ICP-MS) was applied to determine the concentrations of lead (Pb), cadmium (Cd) and arsenic (As) in Lindera aggregata (Sims) Kosterm. The physiologically based extraction test (PBET) digestion in vitro/Caco-2 cell model was established to investigate the bioaccessible contents of Pb, Cd and As in decoction of Lindera aggregata (Sims) Kosterm. The target-organ toxicity dose modification of HI method (TTD) was used to evaluate the cumulative risk caused by the combined exposure of the total levels of Pb, Cd and As in Lindera aggregata (Sims) Kosterm. and the bioaccessible contents in the decoction. The results showed that the total contents of Pb, Cd and As in 4 batches of samples were in the range of 2.901-3.872, 1.299-1.800 and 0.062-0.216 mg·kg^-1, respectively. After transportation by Cacco-2 cells, the bioaccessible contents of Pb, Cd, and As in the decoction were in the range of 0.045-0.080, 0.070-0.112 and 0.004-0.018 mg·kg^-1. The results of risk assessment showed that calculated by the total amounts of heavy metals in the Lindera aggregata (Sims) Kosterm., for the end points of nervous system, the cumulative risks of co-exposure of heavy metals in 3 batches of samples were of concern. After decoction and transportation by Caco-2 cells, for the end points of cardiovascular system, blood, nervous system, kidney and testis, the TTD modification of HI values of all batches of samples were less than 1, and the health risks were acceptable. The study provided methodology basis for a more objective assessment of the health risks of heavy metals and harmful elements in traditional Chinese medicine and for a more scientific limit standard of heavy metals and harmful elements.

Platelets are reprogrammed by cancer via a process called education, which favors cancer development. The transcriptional profile of tumor-educated platelets (TEPs) is skewed and therefore practicable for cancer detection. This intercontinental, hospital-based, diagnostic study included 761 treatment-naïve inpatients with histologically confirmed adnexal masses and 167 healthy controls from nine medical centers (China, n = 3; Netherlands, n = 5; Poland, n = 1) between September 2016 and May 2019. The main outcomes were the performance of TEPs and their combination with CA125 in two Chinese (VC1 and VC2) and the European (VC3) validation cohorts collectively and independently. Exploratory outcome was the value of TEPs in public pan-cancer platelet transcriptome datasets. The AUCs for TEPs in the combined validation cohort, VC1, VC2, and VC3 were 0.918 (95% CI 0.889-0.948), 0.923 (0.855-0.990), 0.918 (0.872-0.963), and 0.887 (0.813-0.960), respectively. Combination of TEPs and CA125 demonstrated an AUC of 0.922 (0.889-0.955) in the combined validation cohort; 0.955 (0.912-0.997) in VC1; 0.939 (0.901-0.977) in VC2; 0.917 (0.824-1.000) in VC3. For subgroup analysis, TEPs exhibited an AUC of 0.858, 0.859, and 0.920 to detect early-stage, borderline, non-epithelial diseases and 0.899 to discriminate ovarian cancer from endometriosis. TEPs had robustness, compatibility, and universality for preoperative diagnosis of ovarian cancer since it withstood validations in populations of different ethnicities, heterogeneous histological subtypes, and early-stage ovarian cancer. However, these observations warrant prospective validations in a larger population before clinical utilities.
Humans ; Female ; Blood Platelets/pathology* ; Biomarkers, Tumor/genetics* ; Ovarian Neoplasms/pathology* ; China

Wuzi-Yanzong-Wan (WZYZW) is a classic prescription for male infertility. Our previous investigation has demonstrated that it can inhibit sperm apoptosis via affecting mitochondria, but the underlying mechanisms are unclear. The purpose of the present study was to explore the actions of WZYZW on mitochondrial permeability transition pore (mPTP) in mouse spermatocyte cell line (GC-2 cells) opened by atractyloside (ATR). At first, WZYZW-medicated serum was prepared from rats following oral administration of WZYZW for 7 days. GC-2 cells were divided into control group, model group, positive group, as well as 5%, 10%, 15% WZYZW-medicated serum group. Cyclosporine A (CsA) was used as a positive control. 50 μmol·L^-1 ATR was added after drugs incubation. Cell viability was assessed using CCK-8. Apoptosis was detected using flow cytometry and TUNEL method. The opening of mPTP and mitochondrial membrane potential (MMP) were detected by Calcein AM and JC-1 fluorescent probe respectively. The mRNA and protein levels of voltage-dependent anion channel 1 (VDAC1), cyclophilin D (CypD), adenine nucleotide translocator (ANT), cytochrome C (Cyt C), caspase 3, 9 were detected by RT-PCR (real time quantity PCR) and Western blotting respectively. The results demonstrated that mPTP of GC-2 cells was opened after 24 hours of ATR treatment, resulting in decreased MMP and increased apoptosis. Pre-protection with WZYZ-medicated serum and CsA inhibited the opening of mPTP of GC-2 cells induced by ATR associated with increased MMP and decreased apoptosis. Moreover, the results of RT-qPCR and WB suggested that WZYZW-medicated serum could significantly reduce the mRNA and protein levels of VDAC1 and CypD, Caspase-3, 9 and CytC, as well as a increased ratio of Bcl/Bax. However, ANT was not significantly affected. Therefore, these findings indicated that WZYZW inhibited mitochondrial mediated apoptosis by attenuating the opening of mPTP in GC-2 cells. WZYZW-medicated serum inhibited the expressions of VDAC1 and CypD and increased the expression of Bcl-2, which affected the opening of mPTP and exerted protective and anti-apoptotic effects on GC-2 cell induced by ATR.
1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine ; Animals ; Atractyloside/pharmacology* ; Cyclophilin D ; Male ; Matrix Metalloproteinases ; Mice ; Mitochondrial Membrane Transport Proteins/metabolism* ; Mitochondrial Permeability Transition Pore ; RNA, Messenger ; Rats

We summarized our experience in transurethral seminal vesiculoscopy (TSV) for recurrent hemospermia by introducing surgical techniques, intraoperative findings, and treatment outcomes. TSV was performed in 419 patients with an initial diagnosis of persistent hemospermia at Shanghai Changhai Hospital (Shanghai, China) from May 2007 to November 2015. TSV was successfully performed in 381 cases (90.9%). Hemospermia was alleviated or disappeared in 324 (85.0%) patients by 3 months after surgery. Common intraoperative manifestations were bleeding, obstruction or stenosis, mucosal lesions, and calculus. Endoscopic presentation of the ejaculatory duct orifice and the verumontanum was categorized into four types, including 8 (1.9%), 32 (7.6%), 341 (81.4%), and 38 (9.1%) cases in Types A, B, C, and D, respectively. TSV is an effective and safe procedure in the management of seminal tract disorders. This study may help other surgeons to become familiar with and improve this procedure. However, further multicentric clinical trials are warranted to validate these findings.
Adult ; Ejaculatory Ducts/surgery* ; Endoscopy/methods* ; Hemospermia/surgery* ; Humans ; Magnetic Resonance Imaging ; Male ; Middle Aged ; Seminal Vesicles/surgery* ; Tomography, X-Ray Computed ; Treatment Outcome ; Urethra/surgery*

BACKGROUNDThe emergency department (ED) has a pivotal influence on the management of acute heart failure (AHF), but data concerning current ED management are scarce. This Beijing AHF Registry Study investigated the characteristics, ED management, and short- and long-term clinical outcomes of AHF.

METHODSThis prospective, multicenter, observational study consecutively enrolled 3335 AHF patients who visited 14 EDs in Beijing from January 1, 2011, to September 23, 2012. Baseline data on characteristics and management were collected in the EDs. Follow-up data on death and readmissions were collected until November 31, 2013, with a response rate of 92.80%. The data were reported as median (interquartile range) for the continuous variables, or as number (percentage) for the categorical variables.

RESULTSThe median age of the enrolled patients was 71 (58-79) years, and 46.84% were women. In patients with AHF, coronary heart disease (43.27%) was the most common etiology, and myocardium ischemia (30.22%) was the main precipitant. Most of the patients in the ED received intravenous treatments, including diuretics (79.28%) and vasodilators (74.90%). Fewer patients in the ED received neurohormonal antagonists, and 25.94%, 31.12%, and 33.73% of patients received angiotensin converting enzyme inhibitors/angiotensin receptor blockers, beta-blockers, and spironolactone, respectively. The proportions of patients who were admitted, discharged, left against medical advice, and died were 55.53%, 33.58%, 7.08%, and 3.81%, respectively. All-cause mortalities at 30 days and 1 year were 15.30% and 32.27%, respectively.

CONCLUSIONSSubstantial details on characteristics and ED management of AHF were investigated. The clinical outcomes of AHF patients were dismal. Thus, further investigations of ED-based therapeutic approaches for AHF are needed.

OBJECTIVENew rationally designed i,i+7-hydrocarbon-stapled peptides that target both HIV-1 assembly and entry have been shown to have antiviral activity against HIV-1 subtypes circulating in Europe and North America. Here, we aimed to evaluate the antiviral activity of these peptides against HIV-1 subtypes predominantly circulating in China.

METHODSThe antiviral activity of three i,i+7-hydrocarbon-stapled peptides, NYAD-36, NYAD-67, and NYAD-66, against primary HIV-1 CRF07_BC and CRF01_AE isolates was evaluated in peripheral blood mononuclear cells (PBMCs). The activity against the CRF07_BC and CRF01_AE Env-pseudotyped viruses was analyzed in TZM-bl cells.

RESULTSWe found that all the stapled peptides were effective in inhibiting infection by all the primary HIV-1 isolates tested, with 50% inhibitory concentration toward viral replication (IC50) in the low micromolar range. NYAD-36 and NYAD-67 showed better antiviral activity than NYAD-66 did. We further evaluated the sensitivity of CRF01_AE and CRF07_BC Env-pseudotyped viruses to these stapled peptides in a single-cycle virus infectivity assay. As observed with the primary isolates, the IC50s were in the low micromolar range, and NYAD-66 was less effective than NYAD-36 and NYAD-67.

CONCLUSIONHydrocarbon-stapled peptides appear to have broad antiviral activity against the predominant HIV-1 viruses in China. This finding may provide the impetus to the rational design of peptides for future antiviral therapy.

Amino Acid Sequence ; Anti-HIV Agents ; chemistry ; pharmacology ; China ; epidemiology ; HIV Envelope Protein gp120 ; genetics ; metabolism ; HIV Infections ; epidemiology ; virology ; HIV-1 ; drug effects ; genetics ; Humans ; Peptides, Cyclic ; administration & dosage ; pharmacology ; Phylogeny

Objective To evaluate the effect of tranexamic acid on the blood loss and coagulation function after liver resection in patients with hepatocellular carcinoma (HCC).Methods Seventy patients with hepatectomy who underwent liver resection were randomly divided into control group and treatment group,each group 35 cases.Control group was given 0.9％ NaCl injection 10 mg · kg-1.Treatment group was given tranexamic acid 10 mg · kg-1.Two groups were used at half an hour before operation.The surgical bleeding volume and postoperative coagulation function between two groups were compared.Results The operation time,time of hilar occlusion in treatment group were (157.98 ±22.36),(30.14 ±5.64) min,had no significant difference with those in control group,which were (154.98 ± 23.65),(28.79 ± 5.79) min (P ＞ 0.05).The surgical blood transfusion,bleeding volume,infusion of erythrocyte suspension in treatment group were (879.65 ± 59.36) mL,(768.97 ± 45.65) mL,(1.36 ± 0.59) U,had significant differences with those in control group,which were (1054.91 ±61.32) mL,(869.64 ±46.69) mL,(2.01 ±0.65) U (all P ＜0.05).The percentage of activated thromboplastin (APTT),prothrombin time (PT),platelet (PLT) in treatment group at 24 h after operation were (41.56 ±5.46)s,(13.48 ±3.16)s,(167.89 ±35.87) × 109/L,had no significant difference with those in control group,which were (43.19 ± 5.69) s,(14.59 ± 2.49) s,(162.35 ± 41.59) × 109/L (all P ＞0.05).The fibrinogen (FIB) in treatment group and control group were (3.27 ±0.56),(3.01 ±0.59)g · L-1,with significant difference (P ＜ 0.05).There was no adverse drug reactions in two groups during the treatment.Conclusion Giving methotrexate injection to hepatocarcinoma patients before liver resection can reduce the amount of surgical bleeding,and improve the patients' postoperative coagulation function.

OBJECTIVETo investigate the clinical application value of 8.5/11.5 F transurethral seminal vesiculoscopy in the diagnosis and treatment of refractory hematospermia.

METHODSWe retrospectively analyzed 78 cases of refractory hematospermia diagnosed and treated by 8.5/11.5 F transurethral seminal vesiculoscopy from June 2012 to June 2014. The patients underwent serum PSA examination, transrectal ultrasonography, seminal vesicle ultrasonography, and pelvis CT or MRI before surgery, and all received transurethral seminal vesiculoscopy under the 8.5/11.5 F rigid ureteroscope.

RESULTSOperations were all successfully accomplished, which revealed abnormal opening of the ejaculatory duct in 5 cases, mucosal inflammatory hyperemia in the prostatic utricle and seminal vesicle in 78, dark red mucilage substance in the seminal vesicle in 34, seminal vesicle stones in 19, small polyp in the seminal vesicle in 2, and ejaculatory duct or seminal vesicle cyst in 4. All the patients received symptomatic treatment during the surgery. After surgery, hematouria was found in 13 cases, which disappeared within 2 weeks, pelvic hematoma in 1 case, which was cured by conservative treatment within 3 months, and epididymitis in 2 cases, which was controlled by anti-infection treatment. Hematospermia recurred in 3 cases during the 1-year postoperative follow-up.

CONCLUSION8.5/11.5 F transurethral seminal vesiculoscopy, with its advantages of easy operation, wide field of vision, large channel for operation, and few complications, deserves general clinical application in the diagnosis and treatment of refractory hematospermia.

Calculi ; Ejaculatory Ducts ; Endoscopy ; methods ; Epididymitis ; etiology ; Hemospermia ; diagnosis ; therapy ; Humans ; Magnetic Resonance Imaging ; Male ; Postoperative Period ; Recurrence ; Retrospective Studies ; Seminal Vesicles ; Tomography, X-Ray Computed ; Urethra