Objective To study the bioequivalence of test and reference olmesartan tablet in Chinese healthy subjects after single dose under fasting and fed conditions.Methods A single-center,random,open,single-dose,two-preparations,double-period,crossover study was adopted.A total of 48 healthy adult male and female subjects(24 cases of fasting test and 24 cases of fed test)were included in the random crossover administration.Single oral dose 20 mg of test and reference were taken under fasting and postprandial conditions,respectively.Plasma concentration of olmesartan in plasma were determined by liquid chromatography tandem mass spectrometry.The main pharmacokinetic parameters were calculated by Phoenix WinNonlin 8.0 software.Results The main pharmacokinetic parameters of the test and reference preparations of olmesartan tablets in the fasting group were as follows:Cmax were(653.06±133.53)and(617.37±151.16)ng·mL-1,AUC0-t were(4 201.18±1 035.21)and(4 087.38±889.99)ng·mL-1·h,AUC0-∞ were(4 254.30±1 058.90)and(4 135.69±905.29)ng·mL-1·h.The main pharmacokinetic parameters of the test and reference preparations of olmesartan tablets in the postprandial group were as follows:Cmax were(574.78±177.05)and(579.98±107.74)ng·mL-1,AUC0-t were(3 288.37±866.06)and(3 181.51±801.06)ng·mL-1·h,AUC0-∞ were(3 326.11±874.26)and(3 242.01±823.09)ng·mL-1·h.Under fasting and postprandial conditions,the 90％confidence intervals of the main pharmacokinetic parameters of the test and reference preparations are both 80.00％-125.00％.Conclusion Under fasting and postprandial conditions,a single oral dose of test and reference preparations olmesartan tablets in Chinese healthy adult volunteers showed bioequivalence.

Aim To study the resistance of SIRT3 ex-pression in dopaminergic neurons against the inflamma-tory damage caused by microglia activation and its re-lated mechanism.Methods Dopaminergic neurons(MN9D cells)and microglia(BV-2 cells)were co-cultured to establish an inflammatory injury model in vitro.MN9D cells were divided into the control group,model group,SIRT3 group and SIRT3+PJ34 group.mRNA levels were analyzed by real-time quantitative polymerase chain reaction,cell apoptosis rate was de-tected by flow cytometry,changes in mitochondrial membrane potential were tested by JC-1 method,and the opening of mitochondrial permeability transport pore(mPTP)was analyzed by co-incubation of calce-in-AM and CoCl2.The protein expression was detected by Western blot.Results Compared to the model group,overexpression of SIRT3 in the SIRT3 group significantly reduced the apoptosis rate of MN9D cells.It also led to a significant increase in the expression of SIRT3 and SOD2 genes,as well as a notable decrease in PARP-1,tumor necrosis factor-α,and interleukin 1β(IL-1β)protein expressions.Moreover,it resulted in a substantial reduction in the p-NF-κB p65/NF-κB p65 ratio.There was an improvement observed in mito-chondrial membrane potential along with decreased mPTP opening and ROS production in the SIRT3 group.These differences among these groups were sta-tistically significant(all P＜0.05).After inhibiting PARP-1 activity of MN9D cells in the SIRT3+PJ34 group,except for the insignificant changes in SIRT3 and IL-1 β protein expression,the changing trend of other indicators was further enhanced on the basis of SIRT3 group.The differences between two groups re-mained statistically significant(all P＜0.05).Con-clusions SIRT3 expression can attenuate the inflam-matory damage of dopaminergic neurons induced by microglia activation,and the mechanism may be relat-ed to improving mitochondrial function,inhibiting PARP-1 activity and NF-κB signaling pathway caused by the reduction of ROS production.

Objective: To observe the characteristics of the evolution of liver indexes in patients with relapsed/refractory multiple myeloma (RRMM) treated with CAR-T-cells based on BCMA. Methods: Retrospective analysis was performed of patients with RRMM who received an infusion of anti-BCMA CAR-T-cells and anti-BCMA combined with anti-CD19 CAR-T-cells at our center between June 1, 2019, and February 28, 2023. Clinical data were collected to observe the characteristics of changes in liver indexes such as alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TBIL), and direct bilirubin (DBIL) in patients, and its relationship with cytokine-release syndrome (CRS) . Results: Ninety-two patients were included in the analysis, including 41 patients (44.6%) in the group receiving a single infusion of anti-BCMA CAR-T-cells, and 51 patients (55.4%) in the group receiving an infusion of anti-BCMA combined with anti-CD19 CAR-T-cells. After infusing CAR-T-cells, 31 patients (33.7%) experienced changes in liver indexes at or above grade 2, which included 20 patients (21.7%) with changes in one index, five patients (5.4%) with changes in two indexes, and six patients (6.5%) with changes in three or more indexes. The median time of peak values of ALT and AST were d17 and d14, respectively, and the median duration of exceeding grade 2 was 5.0 and 3.5 days, respectively. The median time of peak values of TBIL and DBIL was on d19 and d21, respectively, and the median duration of exceeding grade 2 was 4.0 days, respectively. The median time of onset of CRS was d8, and the peak time of fever was d9. The ALT, AST, and TBIL of patients with CRS were higher than those of patients without CRS (P=0.011, 0.002, and 0.015, respectively). CRS is an independent factor that affects ALT and TBIL levels (OR=19.668, 95% CI 18.959-20.173, P=0.001). The evolution of liver indexes can be reversed through anti-CRS and liver-protection treatments, and no patient died of liver injury. Conclusions: In BCMA-based CAR-T-cell therapy for RRMM, CRS is an important factor causing the evolution of liver indexes. The evolution of liver indexes after CAR-T-cell infusion is transient and reversible after treatment.
Humans ; Antigens, CD19 ; B-Cell Maturation Antigen/therapeutic use* ; Bilirubin ; Immunotherapy, Adoptive ; Liver ; Multiple Myeloma/drug therapy* ; Retrospective Studies ; T-Lymphocytes

Objective: To compare the differences between CAS risk model and CHA₂DS₂-VASc risk score in predicting all cause death, thromboembolic events, major bleeding events and composite endpoint in patients with nonvalvular atrial fibrillation. Methods: This is a retrospective cohort study. From the China Atrial Fibrillation Registry cohort study, the patients with atrial fibrillation who were>18 years old were randomly divided into CAS risk score group and CHA₂DS₂-VASc risk score group respectively. According to the anticoagulant status at baseline and follow-up, patients in the 2 groups who complied with the scoring specifications for anticoagulation were selected for inclusion in this study. Baseline information such as age and gender in the two groups were collected and compared. Follow-up was performed periodically to collect information on anticoagulant therapy and endpoints. The endpoints were all-cause death, thromboembolism events and major bleeding, the composite endpoint events were all-cause death and thromboembolism events. The incidence of endpoints in CAS group and CHA₂DS₂-VASc group was analyzed, and multivariate Cox proportional risk model was used to analyze whether the incidence of the endpoints was statistically different between the two groups. Results: A total of 5 206 patients with AF were enrolled, average aged (63.6±12.2) years, and 2092 (40.2%) women. There were 2 447 cases (47.0%) in CAS risk score group and 2 759 cases (53.0%) in CHA₂DS₂-VASc risk score group. In the clinical baseline data of the two groups, the proportion of left ventricular ejection fraction<55%, non-paroxysmal atrial fibrillation, oral warfarin and HAS BLED score in the CAS group were lower than those in the CHA₂DS₂-VASc group, while the proportion of previous diabetes history and history of antiplatelet drugs in the CAS group was higher than that in the CHA₂DS₂-VASc group, and there was no statistical difference in other baseline data. Patients were followed up for (82.8±40.8) months. In CAS risk score group, 225(9.2%) had all-cause death, 186 (7.6%) had thromboembolic events, 81(3.3%) had major bleeding, and 368 (15.0%) had composite endpoint. In CHA₂DS₂-VASc risk score group, 261(9.5%) had all-cause death 209(7.6%) had thromboembolic events, 112(4.1%) had major bleeding, and 424 (15.4%) had composite endpoint. There were no significant differences in the occurrence of all-cause death, thromboembolic events, major bleeding and composite endpoint between anticoagulation in CAS risk score group and anticoagulation in CHA₂DS₂-VASc risk score group (log-rank P =0.643, 0.904, 0.126, 0.599, respectively). Compared with CAS risk score, multivariable Cox proportional hazards regression models showed no significant differences for all-cause death, thromboembolic events, major bleeding and composite endpoint between the two groups with HR(95%CI) 0.95(0.80-1.14), 1.00(0.82-1.22), 0.83(0.62-1.10), 0.96(0.84-1.11), respectively. All P>0.05. Conclusions: There were no significant differences between CAS risk model and CHA₂DS₂-VASc risk score in predicting all-cause death, thromboembolic events, and major bleeding events in Chinese patients with non-valvular atrial fibrillation.
Adolescent ; Anticoagulants ; Atrial Fibrillation/drug therapy* ; Cohort Studies ; Female ; Hemorrhage/complications* ; Humans ; Male ; Retrospective Studies ; Risk Assessment ; Stroke/epidemiology* ; Stroke Volume ; Thromboembolism/etiology* ; Ventricular Function, Left

Objective: To evaluate the efficacy of in-situ full size split liver transplantation(fSLT) for adult recipients using the living donor liver transplantation(LDLT) technique and to compare the characteristics of the left hemiliver graft (LHG) and the right hemiliver graft(RHG)transplantation. Methods: Deceased donor and recipient data of 25 consecutive cases of fSLT at Department of Hepatopancreatobiliary Surgery, Ningbo Medical Center Lihuili Hospital from March to December 2021 was retrieved and the patients divided into two groups:LHG group and RHG group. Among the 13 donors,11 were male and 2 were female,aged (M(IQR))38(19) years(range: 25 to 56 years),with height of 168(5) cm(range:160 to 175 cm) and weight of 65(9) kg(range: 50 to 75 kg). The median age of the 25 recipients was 52(14) years(range:35 to 71 years),17 were male and 8 were female,15 had primary liver cancer and 10 had benign end-stage liver disease,model for end-stage liver disease score was 10(9) points(range:7 to 23 points). Of the 25 recipients,10 recipients had previously undergone hepatobiliary surgery. The follow-up period was to January 2022. Demographic,clinicopathological,surgical outcomes and postoperative complications were evaluated and compared between the two groups. Continuous quantitative data were compared using Mann-Whitney U test. Classification data were expressed as frequencies,and were compared between groups using χ² test or Fisher exact probability method. Results: Using LDLT technique,in-situ full-left/full-right liver splitting was performed and 13 viable pairs of hemiliver grafts were harvested with acquisition time of 230(53) minutes(range:125 to 352 minutes) and blood loss of 250(100) ml(range:150 to 1 000 ml). A total of 25 hemiliver grafts(13 LHG and 12 RHG) were allocated to patients listed for liver transplantation in our center by China Organ Transplant Response System. In the LHG group(13 cases),there were more females and more patients with benign end-stage liver disease than in the RHG group(12 cases)(P<0.05). The body weight and graft weight of recipients in the LHG group were lower than that in RHG group(both P<0.05). There were no significant differences in other baseline data between the two groups(all P>0.05). The graft to recipient weight ratio(GRWR) was 1.2(0.4)%(range:0.7% to 1.9%) for 25 recipients,1.1(0.5)%(range:0.7% to 1.6%)for the LHG group and 1.3(0.5)%(range:0.9% to 1.9%)for the RHG group. There was no significant difference between the two groups (P>0.05). Sharing patterns of hepatic vessels and the common bile duct are as follows:all the trunk of middle hepatic vein were allocated to the LHG group. The proportion of celiac trunk,main portal vein and common bile duct assigned to LHG and RHG was 10∶3 (P=0.009), 9∶4 (P>0.05) and 4∶9 (P=0.027),respectively. The vena cava of 12 donors in early stage retained in LHG and that of last one was shared between LHG and RHG (P<0.01). The median cold ischemia time of 25 hemiliver grafts was 240(90) minutes(range:138 to 420 minutes). For the total of 25 fSLT,the median anhepatic phase was 50(16) minutes(range:31 to 98 minutes) and the operation time was 474(138)minutes(range:294 to 680 minutes) with blood loss of 800(640) ml(range:200 to 5 000 ml). There were no significant differences in all of operation data between two groups. In the LHG group,3 patients with GRWR≤0.8% had postoperative small-for-size syndrome which improved after treatment. Postoperative Clavien-Dindo grade≥Ⅲ complications were observed in 6 cases(24.0%),4 cases(4/13) in the LHG group and 2 cases(2/12) in the RHG group,respectively. The difference was not statistically significant. Among them,5 cases improved after re-operation and intervention,1 case in LHG group died of secondary infection 2 weeks after operation,and the mortality was 4.0%. Analysis of serious postoperative complications and death has suggested that conventional caval interposition should not be used for LHG transplantation. Conclusion: Relying on accurate donor-recipient evaluation and the apply of LDLT technique,the morbidity and mortality of in-situ fSLT in adults is acceptable.
Adult ; Aged ; End Stage Liver Disease/surgery* ; Female ; Humans ; Liver/surgery* ; Liver Transplantation/methods* ; Living Donors ; Male ; Middle Aged ; Postoperative Complications ; Retrospective Studies ; Severity of Illness Index ; Treatment Outcome

Objective: To evaluate the safety and effectiveness of left atrial appendage occlusion (LAAO) in patients with atrial fibrillation and end-stage renal disease undergoing long-term hemodialysis. Methods: Six patients with AF and end-stage renal disease(ESRD)on long term hemodialysis who underwent LAAO from March 2017 to March 2021 in Beijing Anzhen Hospital were enrolled. Baseline characteristics such as age, sex, types of arrhythmia, stroke and bleeding score, and continuous dialysis time were collected. Four patients underwent LAAO, two patients underwent the combined procedure of catheter ablation and LAAO. Perioperative treatment and serious complications were recorded. Transesophageal echocardiography was repeated at 45 days and 60 days after the procedure. Telephone follow-up was conducted at 3, 6 and 12 months after the procedure, and every 6 months thereafter. Thromboembolism and major bleeding events and survival were evaluated. Results: The average age was (66.7±17.0) years old, and 5 were male (5/6). There were 4 patients with paroxysmal AF (4/6), and 2 patients with persistent AF (2/6). The mean CHA₂DS₂-VASc score was (4.8±1.5), and the HAS-BLED score was (3.5±1.4). The duration of hemodialysis was 2.6 (1.1, 8.3) years. Successfully Watchman implantation was achieved in all patients. There were no severe perioperative complications, and no device related thrombosis or leaks were observed by transesophageal echocardiography. During a mean of 22.0 (12.0, 32.0) months follow-up, there was no thromboembolism or major bleeding events. A total of 2 patients died, one from sudden cardiac death, and another one from heart failure. Conclusions: LAAO may be a safe and effective therapeutic option for prevention of thromboembolism in patients with atrial fibrillation and end-stage renal disease undergoing long-term hemodialysis, further studies with larger patient cohort are needed to confirm our results.
Aged ; Aged, 80 and over ; Atrial Appendage/surgery* ; Atrial Fibrillation/surgery* ; Echocardiography, Transesophageal ; Humans ; Kidney Failure, Chronic/therapy* ; Male ; Middle Aged ; Renal Dialysis ; Stroke ; Thromboembolism ; Treatment Outcome

Objective To investigate the efficiency of various agroforestry systems for snail control in plateau hilly schistosomiasis-endemic areas of Yunnan Province, so as to provide insights into the construction of agroforestry schistosomiasis control projects in plateau hilly regions. Methods The pilot areas of snail control forests with various agroforestry systems were built in snail-breeding farmlands in Eryuan County, Yunnan Province in 2010, and the economic benefits and snail control effect were investigated in 2018. In addition, a fuzzy comprehensive evaluation model was created to screen the agroforestry system with high comprehensive benefits. Results A total of 14 types of pilot areas of snail control forests with various agroforestry systems were built. Economic benefit analysis showed that the“walnut + garlic”pattern had the best economic benefit, with annual economic benefits of 270 000 Yuan/hm², followed by the“walnut + chili”pattern (annual economic benefits of 120 000 Yuan/hm²) and the “walnut + vegetables”pattern (annual economic benefits of 105 000 Yuan/hm²). No snails were detected in 8 types of the agroforestry systems, including the“walnut + chili”pattern, the“walnut + tobacco”pattern and the“walnut + garlic”pattern; however, there were snail found with various densities in other types of systems. Fuzzy comprehensive evaluation showed that the“walnut + garlic”pattern had the best comprehensive control effect, followed by the“walnut + chili”pattern and the“walnut + tobacco” pattern, while the pure grassland pattern showed no effect on snail control. Conclusions The agroforestry system is a preferential approach of forestry schistosomiasis control in plateau hilly schistosomiasis-endemic areas, which not only achieves snail control effects, but also promotes economic development and ecological construction in poor hilly areas.

Objective: Several COVID-19 patients have overlapping comorbidities. The independent role of each component contributing to the risk of COVID-19 is unknown, and how some non-cardiometabolic comorbidities affect the risk of COVID-19 remains unclear. Methods: A retrospective follow-up design was adopted. A total of 1,160 laboratory-confirmed patients were enrolled from nine provinces in China. Data on comorbidities were obtained from the patients' medical records. Multivariable logistic regression models were used to estimate the odds ratio ( Results: Overall, 158 (13.6%) patients were diagnosed with severe illness and 32 (2.7%) had unfavorable outcomes. Hypertension (2.87, 1.30-6.32), type 2 diabetes (T2DM) (3.57, 2.32-5.49), cardiovascular disease (CVD) (3.78, 1.81-7.89), fatty liver disease (7.53, 1.96-28.96), hyperlipidemia (2.15, 1.26-3.67), other lung diseases (6.00, 3.01-11.96), and electrolyte imbalance (10.40, 3.00-26.10) were independently linked to increased odds of being severely ill. T2DM (6.07, 2.89-12.75), CVD (8.47, 6.03-11.89), and electrolyte imbalance (19.44, 11.47-32.96) were also strong predictors of unfavorable outcomes. Women with comorbidities were more likely to have severe disease on admission (5.46, 3.25-9.19), while men with comorbidities were more likely to have unfavorable treatment outcomes (6.58, 1.46-29.64) within two weeks. Conclusion Besides hypertension, diabetes, and CVD, fatty liver disease, hyperlipidemia, other lung diseases, and electrolyte imbalance were independent risk factors for COVID-19 severity and poor treatment outcome. Women with comorbidities were more likely to have severe disease, while men with comorbidities were more likely to have unfavorable treatment outcomes.
Adult ; Aged ; COVID-19/virology* ; China/epidemiology* ; Comorbidity ; Female ; Humans ; Male ; Middle Aged ; Retrospective Studies ; Severity of Illness Index ; Treatment Outcome

The pig bile powder, bovine bile powder, snake bile, sheep bile, goose bile powder, and bear bile powder were contained by the Chinese Pharmacopoeia. The bile power medicine has a long history in traditional Chinese medicine and definite effect. However, the medicine of bile powder(bile) are similar in morphology. Besides, many medicine lack specific microscopic identification characteristics and chemical characteristics. There is a risk of adulteration, especially when the fake medicine were mixed in authentic medicine, it is difficult to detection. The key to control the quality and ensures the clinical efficacy is the good or bad, true or false of the bile power medicine. The STR typing technology is a method that according to differential typing of PCR amplified lengths to compare and identify individual organisms. Based on the principle of STR typing, the easily, rapid DNA fingerprinting method to identify the bile power and adulteration was established.The original animal or bile powder of pigs, cattle, sheep, chickens, ducks, geese, snakes, bears, fish were collected, the 12 S-L1091/12 S-H1478 and 16 S-L3428/16 S-H3667 was obtained by sifted, the DNA fingerprinting of the bile power and adulteration was obtained by STR typing. Every species has different STR fingerprints, so different species can be identified. Besides, the fingerprints have both the authentic and fake's information, the adulteration of authentic and fake can be identified. Therefore, the method to identify the bile power and adulteration was achieved through the combination of two primers. The DNA fingerprinting method established in this study can also be used for other animal medicine.
Animals ; Bile/chemistry* ; Cattle ; Chickens ; DNA Fingerprinting ; Materia Medica/analysis* ; Medicine, Chinese Traditional ; Sheep ; Swine ; Ursidae

Aim To investigate the role of SIRT3 in the molecular mechanism of melatonin protecting do-paminergic neurons in Parkinson' s disease ( PD). Methods Forty-eight mice were randomly divided into control group, model group and treatment group. The mice in treatment group received intraperitoneal injection of melatonin (10 mg • kg"1) and MPTP (30 mg • kg ~1). The mice in model group only received intraperitoneal injection of MPTP (30 mg • kg~1 ) , and the mice in control group received the same a-mount of normal saline. Melatonin was administered continuously for 14 days. The expressions of TH and lba-1 in substantia nigra were analyzed by immunohis-tochemistry. The levels of oxidative stress ( ROS, MDA, SOD) and inflammatory factors (TNF-a, IL-lp) in the midbrain were measured by ELISA. SIRT3 mRNA level was analyzed by qRT-PCR, and protein expression level was detected by immunocytochemistry assay and Western blot. Results Compared to control group, the TH expression decreased and Iba-1 expression increased in the substantia nigra, the oxidative stress and inflammatory injury in the midbrain were significantly enhanced, the SIRT3 mRNA and protein levels in the substantia nigra obviously declined, the SOD2 protein expression was also dramatically reduced, and the iNOS protein expression was elevated in model group; the differences between the groups were all statistically significant ( P < 0. 05 ). After treatment with melatonin, the TH expression increased, Iba-1 expression decreased, oxidative stress and inflammatory injury markedly decreased, SIRT3 mRNA and protein levels were elevated, SOD2 protein expression was up-regulated, and iNOS protein expression was down-regulated in treatment group. Compared to model group, the differences were all statistically significant ( P < 0.05). Conclusions Melatonin can counteract the damage of dopaminergic neurons by up-regulating the expression of SIRT3 in PD animal model. Its mechanisms of action are related to inhibiting microglia activation, and alleviating oxidative stress and inflammation injury.