Objective To investigate the toxicokinetic differences of 3,4-methylenedioxy-N-methylamphetamine(MDMA)and its metabolite 4,5-methylene dioxy amphetamine(MDA)in rats af-ter single and continuous administration of MDMA,providing reference data for the forensic identifica-tion of MDMA.Methods A total of 24 rats in the single administration group were randomly divided into 5,10 and 20 mg/kg experimental groups and the control group,with 6 rats in each group.The ex-perimental group was given intraperitoneal injection of MDMA,and the control group was given intraperi-toneal injection of the same volume of normal saline as the experimental group.The amount of 0.5 mL blood was collected from the medial canthus 5 min,30 min,1 h,1.5 h,2 h,4 h,6 h,8 h,10 h,12 h after administration.In the continuous administration group,24 rats were randomly divided into the experi-mental group(18 rats)and the control group(6 rats).The experimental group was given MDMA 7 d by continuous intraperitoneal injection in increments of 5,7,9,11,13,15,17 mg/kg per day,respectively,while the control group was given the same volume of normal saline as the experimental group by in-traperitoneal injection.On the eighth day,the experimental rats were randomly divided into 5,10 and 20 mg/kg dose groups,with 6 rats in each group.MDMA was injected intraperitoneally,and the con-trol group was injected intraperitoneally with the same volume of normal saline as the experimental group.On the eighth day,0.5 mL of blood was taken from the medial canthus 5 min,30 min,1 h,1.5 h,2 h,4 h,6 h,8 h,10 h,12 h after administration.Liquid chromatography-triple quadrupole tandem mass spectrometry was used to detect MDMA and MDA levels,and statistical software was employed for data analysis.Results In the single-administration group,peak concentrations of MDMA and MDA were reached at 5 min and 1 h after administration,respectively,with the largest detection time limit of 12 h.In the continuous administration group,peak concentrations were reached at 30 min and 1.5 h af-ter administration,respectively,with the largest detection time limit of 10 h.Nonlinear fitting equations for the concentration ratio of MDMA and MDA in plasma and administration time in the single-administration group and continuous administration group were as follows:T=10.362C-1.183,R2=0.974 6;T=7.397 3C-0.694,R2=0.961 5(T:injection time;C:concentration ratio of MDMA to MDA in plasma).Conclusions The toxicokinetic data of MDMA and its metabolite MDA in rats,obtained through single and continuous administration,including peak concentration,peak time,detection time limit,and the relationship between concentration ratio and administration time,provide a theoretical and data foundation for relevant forensic identification.

The hemodynamic characteristics of venous reflux are associated with infertility in patients with varicocele; however, an effective method for quantifying the structural distribution of the reflux is lacking. This study aimed to predict surgical outcomes using a new software for venous reflux quantification. This was a retrospective cohort study of a consecutive series of 105 patients (age range: 22-44 years) between July 2017 and September 2019. Venous reflux of the varicocele was obtained using the Valsalva maneuver during scrotal Doppler ultrasonography before microsurgical varicocelectomy. Using this software, the colored reflux signals were segmented, and the gray scale of the color pixels representing the reflux velocity was comprehensively quantified into the mean reflux velocity of the green layer (MRVG) and the reflux velocity standard deviation of the green layer (RVSDG). Spontaneous pregnancy and changes from baseline in the semen parameters were assessed during a 12-month follow-up period. Data were analyzed using logistic regression analysis. An association of the high MRVG group with impaired progressive motility (odds ratio [OR] = 2.868, 95% confidence interval [CI]: 1.133-7.265) and impaired sperm concentration (OR = 2.943, 95% CI: 1.196-7.239) was found during multivariate analysis. High MRVG (OR = 2.680, 95% CI: 1.086-6.614) and high RVSDG (OR = 2.508, 95% CI: 1.030-6.111) were found to be independent predictors of failure to achieve pregnancy following microsurgical repair. In summary, intense venous reflux is an independent predictor of impaired progressive motility, sperm concentration, and pregnancy outcomes after microsurgical varicocelectomy.
Pregnancy ; Female ; Humans ; Male ; Young Adult ; Adult ; Varicocele/surgery* ; Retrospective Studies ; Semen ; Veins/surgery* ; Sperm Count ; Infertility, Male/surgery* ; Microsurgery/methods* ; Sperm Motility

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

Fourteen new geranyl phenyl ethers (1-14) along with three known compounds (15-17) were isolated from Illicium micranthum, and their structures were elucidated by comprehensive spectroscopic methods. Illimicranins A-H (1-8) were characterized as geranyl vanillin ethers, while 9 and 10 were dimethyl acetal derivatives. Illimicranins I and J (11 and 12) were rare geranyl isoeugenol ethers. Illimicranins K and L (13 and 14) represented the first example of geranyl guaiacylacetone ether and geranyl zingerone ether, respectively. Compounds 1, 2 and 15 exhibited anti-HBV (hepatitis B virus) activity against HBsAg (hepatitis B surface antigen) and HBeAg (hepatitis B e antigen) secretion, and HBV DNA replication.
Antiviral Agents/pharmacology* ; Hepatitis B Surface Antigens ; Hepatitis B e Antigens ; Illicium/chemistry* ; Phenyl Ethers

Humans ; COVID-19 ; Consensus ; SARS-CoV-2 ; China

Objective: To explore the changes of γ-GCS mRNA expression and GSH-PX in serum of workers exposed to manganese in order to provide scientific basis for early diagnosis of manganese poisoning. Methods: In June 2017, a total of 180 workers from a motorcycle manufacturer were selected by stratified random sampling, including 115 welders as the exposure group and 65 administrative office workers as the Control Group, the exposure group was divided into high exposure group (43 persons) and low exposure group (72 persons) according to whether the exposure group exceeded the standard limit. The levels of γ-gcs Mrna expression and GSH-Px activity in serum were determined by Occupational Health Survey, and the differences of γ-gcs Mrna expression and GSH-Px activity among different groups were analyzed. Results: Compared with the control group, the serum GSH-Px activity was lower and the serum γ-GCS mRNA expression level was higher in the exposed group (F=370.52, 275.95, P<0.01) . Compared with the control group, there was significant difference in γ-GCS mRNA expression level and GSH-Px activity (F=0.475、1.06, P<0.01; F=48.53、111.70, P<0.01) . The concentrations of manganese in air, welding dust and urine were positively correlated with the level of γ-GCS mRNA (r=0.71, 0.50, 0.31, P<0.01) The serum GSH-Px activity was negatively correlated with the concentrations of manganese in air, welding dust and urine (r=-0.80, -0.52, -0.30, P< 0.01) , There was no correlation between Serum γ-GSH-Px activity and age and years of exposure (P>0.05) . Conclusion: Serum γ-GCS mRNA expression level and GSH-Px activity level can be used as early biomarkers of manganese poisoning. The concentrations of manganese in workplace air, welding dust and urine manganese in workers are the influencing factors.
Air Pollutants, Occupational ; Dust ; Humans ; Ions ; Manganese ; Manganese Poisoning ; Occupational Exposure/analysis* ; RNA, Messenger/genetics* ; Welding

Aim To evaluate the protective effect of α-asarone on microglials with cerebral ischemia/reperfusion injury by measuring the expression of polar transformation and related inflammatory proteins in BV2 cells in vitro and its mechanisms.Methods The cerebral ischemia/reperfusion injury BV2 cells were pretreated by α-asarone in vitro and simulated by OGD/R model.The effect of α-asarone on the viability of damaged cells in OGD/R model was determined by CCK-8; the morphological changes of cells were observed to analyze the general morphology of cells; the levels of proinflammatory factor IL-1β, IL-18 and anti-inflammatory factor IL-10, IL-4, and ROS activity secreted by BV2 cells were detected by ELISA; the protein expressions of TGF-β, TNF-α and inflammatory related protein NLRP3, caspase 1, p-NF-κB were detected by Western blot.Results The results of in vitro experiments were as follows: the activity of damaged cells in OGD/R model was significantly increased by α-asarone, with the increase of administration dose, the cells in the low, medium and high dose groups of α-asarone decreased, and the "amoeba-like" cells and the cell body were gradually became stereoscopic and full.From the results of cell morphology, it could be seen that α-asarone had a certain proliferative effect on normal cells; the release was significantly reduced of proinflammatory factor IL-1β, IL-18 and TNF-α in OGD/R injured BV2 cells pretreated with α-asarone, also increased the release of IL-10, IL-4 and TGF-β, with a dose-effect relationship, and the high dose(16 μmol·L-1)was the best; the expressions of inflammatory related protein NLRP3, caspase 1, NF-κB and ROS activity in injured cells of OGD/R model were significantly reduced after pretreatment with α-asarone.Conclusions α-asarone has a significant protective effect on cerebral ischemia/reperfusion injury, mainly by regulating ROS activity and inhibiting phosphorylation of NF-κB, in order to reduce the excessive activation of NLRP3 inflammatory corpuscles reducing the secretion of proinflammatory factor IL-1β and IL-18, promoting the secretion of anti-inflammatory factor IL-10 and IL-4, so as to protect cerebral ischemia/reperfusion injury by anti-inflammatory reaction.

Objective: To explore the effect of perioperative chemotherapy on the prognosis of gastric cancer patients under real-world condition. Methods: A retrospective cohort study was carried out. Real world data of gastric cancer patients receiving perioperative chemotherapy and surgery + adjuvant chemotherapy in 33 domestic hospitals from January 1, 2014 to January 31, 2016 were collected. Inclusion criteria: (1) gastric adenocarcinoma was confirmed by histopathology, and clinical stage was cT2-4aN0-3M0 (AJCC 8th edition); (2) D2 radical gastric cancer surgery was performed; (3) at least one cycle of neoadjuvant chemotherapy (NAC) was completed; (4) at least 4 cycles of adjuvant chemotherapy (AC) [SOX (S-1+oxaliplatin) or CapeOX (capecitabine + oxaliplatin)] were completed. Exclusion criteria: (1) complicated with other malignant tumors; (2) radiotherapy received; (3) patients with incomplete data. The enrolled patients who received neoadjuvant chemotherapy and adjuvant chemotherapy were included in the perioperative chemotherapy group, and those who received only postoperative adjuvant chemotherapy were included in the surgery + adjuvant chemotherapy group. Propensity score matching (PSM) method was used to control selection bias. The primary outcome were overall survival (OS) and progression-free survival (PFS) after PSM. OS was defined as the time from the first neoadjuvant chemotherapy (operation + adjuvant chemotherapy group: from the date of operation) to the last effective follow-up or death. PFS was defined as the time from the first neoadjuvant chemotherapy (operation + adjuvant chemotherapy group: from the date of operation) to the first imaging diagnosis of tumor progression or death. The Kaplan-Meier method was used to estimate the survival rate, and the Cox proportional hazards model was used to evaluate the independent effect of perioperative chemo therapy on OS and PFS. Results: 2 045 cases were included, including 1 293 cases in the surgery+adjuvant chemotherapy group and 752 cases in the perioperative chemotherapy group. After PSM, 492 pairs were included in the analysis. There were no statistically significant differences in gender, age, body mass index, tumor stage before treatment, and tumor location between the two groups (all P>0.05). Compared with the surgery + adjuvant chemotherapy group, patients in the perioperative chemotherapy group had higher proportion of total gastrectomy (χ(2)=40.526, P<0.001), smaller maximum tumor diameter (t=3.969, P<0.001), less number of metastatic lymph nodes (t=1.343, P<0.001), lower ratio of vessel invasion (χ(2)=11.897, P=0.001) and nerve invasion (χ(2)=12.338, P<0.001). In the perioperative chemotherapy group and surgery + adjuvant chemotherapy group, 24 cases (4.9%) and 17 cases (3.4%) developed postoperative complications, respectively, and no significant difference was found between two groups (χ(2)=0.815, P=0.367). The median OS of the perioperative chemotherapy group was longer than that of the surgery + adjuvant chemotherapy group (65 months vs. 45 months, HR: 0.74, 95% CI: 0.62-0.89, P=0.001); the median PFS of the perioperative chemotherapy group was also longer than that of the surgery+adjuvant chemotherapy group (56 months vs. 36 months, HR=0.72, 95% CI:0.61-0.85, P<0.001). The forest plot results of subgroup analysis showed that both men and women could benefit from perioperative chemotherapy (all P<0.05); patients over 45 years of age (P<0.05) and with normal body mass (P<0.01) could benefit significantly; patients with cTNM stage II and III presented a trend of benefit or could benefit significantly (P<0.05); patients with signet ring cell carcinoma benefited little (P>0.05); tumors in the gastric body and gastric antrum benefited more significantly (P<0.05). Conclusion: Perioperative chemotherapy can improve the prognosis of gastric cancer patients.
Chemotherapy, Adjuvant ; Female ; Gastrectomy ; Humans ; Male ; Neoadjuvant Therapy ; Neoplasm Staging ; Prognosis ; Retrospective Studies ; Stomach Neoplasms/surgery*

Objective: To analyze the current adherence to imatinib in patients with gastrointestinal stromal tumors (GIST) in China and its influencing factors. Methods: A cross-sectional survey was conducted. Study period: from October 1, 2020 to November 31, 2020. Study subjects: GIST patients taking imatinib who were diagnosed and treated in public tertiary level A general hospitals or oncology hospitals; those who had not been pathologically diagnosed, those who never received imatinib, or those who had taken imatinib in the past but stopped afterwards were excluded. The Questionnaire Star online surgery platform was used to design a questionnaire about the adherence to adjuvant imatinib therapy of Chinese GIST patients. The link of questionnaire was sent through WeChat. The questionnaire contained basic information of patients, medication status and Morisky Medication Adherence Scale. Results: A total of 2162 questionnaires from 31 provinces, autonomous regions, and municipalities were collected, of which 2005 were valid questionnaires, with an effective rate of 92.7%. The survey subjects included 1104 males and 901 females, with a median age of 56 (22-91) years old. Working status: 609 cases (30.4%) in the work unit, 729 cases (36.4%) of retirement, 667 cases of flexible employment or unemployment (33.3%). Education level: 477 cases (23.8%) with bachelor degree or above, 658 cases (32.8%) of high school, 782 cases (39.0%) of elementary or junior high school, 88 cases (4.4%) without education. Marital status: 1789 cases (89.2%) were married, 179 cases (8.9%) divorced or widowed, 37 cases (1.8%) unmarried. Two hundred and ninety-four patients (14.7%) had metastasis when they were first diagnosed, including 203 liver metastases, 52 peritoneal metastases, and 39 other metastases. One thousand eight hundred and sixty-nine patients underwent surgical treatment, of whom 1642 (81.9%) achieved complete resection. The median time of taking imatinib was 25 (1-200) months. Common adverse reactions of imatinib included 1701 cases (84.8%) of periorbital edema, 1031 cases (51.4%) of leukopenia, 948 cases (47.3%) of fatigue, 781 cases (39.0%) of nausea and vomiting, 709 cases (35.4%) of rash, and 670 cases (33.4%) of lower extremity edema. The score of the Morisky Medication Adherence Scale showed that 392 cases (19.6%) had poor adherence, 1023 cases (51.0%) had moderate adherence, and 590 cases (29.4%) had good adherence. Univariate analysis showed that gender, age, work status, economic income, residence, education level, marriage, the duration of taking medication and adverse reactions were associated with adherence to adjuvant imatinib therapy (all P<0.05). Multivariate analysis showed that female (OR=1.264, P=0.009), non-retirement (OR=1.454, P=0.001), monthly income ≤4000 yuan (OR=1.280, P=0.036), township residents (OR=1.332, P=0.005), unmarried or divorced or widowed (OR=1.362, P=0.026), the duration of imatinib medication >36 months (OR=1.478, P<0.001) and adverse reactions (OR=1.719, P=0.048) were independent risk factors for poor adherence to adjuvant imatinib. Among patients undergoing complete resection, 324 (19.7%) had poor adherence, 836 (50.9%) had moderate adherence, and 482 (29.4%) had good adherence. Meanwhile, 55 patients with good adherence (11.4%) developed recurrence after surgery, 121 patients with moderate adherence (14.5%) developed recurrence, 61 patients with poor adherence (18.8%) developed recurrence, and the difference was statistically significant (P=0.017). Conclusions: The adherence to adjuvant therapy with imatinib in Chinese GIST patients is relatively poor. Females, non-retirement, monthly income ≤4000 yuan, township residents, unmarried or divorced or widowed, the duration of imatinib medication >36 months, and adverse reactions are independently associated with poor adherence of GIST patients. Those with poor adherence have a higher risk of recurrence after surgery. Positive interventions based on the above risk factors are advocated to improve the prognosis of patients with GIST.
Aged ; Aged, 80 and over ; Antineoplastic Agents/therapeutic use* ; Chemotherapy, Adjuvant ; Cross-Sectional Studies ; Female ; Gastrointestinal Stromal Tumors/drug therapy* ; Humans ; Imatinib Mesylate/therapeutic use* ; Male ; Middle Aged ; Neoplasm Recurrence, Local/drug therapy*

Objective:To observe any effect of endoscopic evaluation of swallowing (FEES) on the functional outcomes of post-stroke patients in the subacute phase.Methods:A retrospective case-control study was conducted of 52 patients who had received an FEES assessment (the FEES group) and 51 who had not (the control group). Both groups received swallowing rehabilitation and intake training based on the results of the FEES assessment and those of a modified volume-viscosity swallowing test. The primary outcome indicator was the incidence of pneumonia. Secondary outcome indicators were the rate of removal of the nasal feeding tube, the length of indwelling of the nasal feeding tube, functional oral intake assessment scale (FOIS) scores, eating technique at discharge, and the length of hospital stay.Results:Compared with the control group, the incidence of pneumonia in the FEES group was significantly lower (7.7% vs. 39.2%). The removal rate of the nasal feeding tube was significantly greater (75.0% vs. 41.0%). The FEES group showed a significant improvement in its average FOIS score. And the proportion of patients who could try partial oral eating or complete oral eating at discharge was significantly higher in the FEES group. Regression analysis indicated that the risk of pneumonia in the FEES group was positively related to the time from onset to the first FEES examination.Conclusion:Early FEES examination after a stroke could reduce the incidence of pneumonia, increase chances of removing the nasal feeding tube and improve the swallowing function and outcome of stroke survivors.