Objective To establish a method and study the pharmacokinetics for concentration determination of effective components in Xiakucao Xiaoliu mixture in Normal Rat Plasma By LC-MS/MS. Methods The mobile phase was methanol-water (0.1% formic acid) system under the positive ion mode of C18 chromatographic column, gradient elution was adopted, and the flow rate was 0.3 ml/min. In the negative ion mode, the mobile phase was acetonitrile-water (0.1% formic acid) system, gradient elution, with a flow rate of 0.4 ml/min. Caffeic acid, rosmarinic acid, syringic acid, rutin in positive ion mode and Atractylodes lactone II and Atractylodes lactone III in negative ion mode were respectively determined. Normal rats were intragastrically given Xiakucao Xiaoliu Mixture 7.8 ml/kg, and blood was taken from the orbit at different time points after the administration. The blood concentration was determined by the validated LC-MS/MS method and the non-standard DAS2.0 software was used. The pharmacokinetic parameters of rats after administration were calculated by the compartment model. Results The pharmacokinetic parameters belonged to non atrioventricular model. The pharmacokinetic characteristics of the four main anti-cancer active ingredients of Caffeic acid, Rosmarinic acid, Syringic acid and Atractylodes Ⅲ in rats after administration of Xiakucao Xiaoliu Mixture were significantly different from those reported in the literature after the administration of monomers. Conclusion The established method was simple, accurate and sensitive, which could be suitable for the content determination of effective components in Xiakucao Xiaoliu mixture in Normal Rat Plasma, which would be a valuable information for the study on main anticancer active substances.

Venous thromboembolism (VTE) is a complication in children with acute lymphoblastic leukemia (ALL). The Chinese Children's Cancer Group-ALL-2015 protocol was carried out in China, and epidemiology, clinical characteristics, and risk factors associated with VTE were analyzed. We collected data on VTE in a multi-institutional clinical study of 7640 patients with ALL diagnosed in 20 hospitals from January 2015 to December 2019. First, VTE occurred in 159 (2.08%) patients, including 90 (56.6%) during induction therapy and 108 (67.92%) in the upper extremities. T-ALL had a 1.74-fold increased risk of VTE (95% CI 1.08-2.8, P = 0.022). Septicemia, as an adverse event of ALL treatment, can significantly promote the occurrence of VTE (P < 0.001). Catheter-related thrombosis (CRT) accounted for 75.47% (n = 120); and, symptomatic VTE, 58.49% (n = 93), which was more common in patients aged 12-18 years (P = 0.023), non-CRT patients (P < 0.001), or patients with cerebral thrombosis (P < 0.001). Of the patients with VTE treated with anticoagulation therapy (n = 147), 4.08% (n = 6) had bleeding. The VTE recurrence rate was 5.03% (n = 8). Patients with VTE treated by non-ultrasound-guided venous cannulation (P = 0.02), with residual thrombus (P = 0.006), or with short anticoagulation period (P = 0.026) had high recurrence rates. Thus, preventing repeated venous puncture and appropriately prolonged anticoagulation time can reduce the risk of VTE recurrence.
Humans ; Child ; Venous Thromboembolism/etiology* ; East Asian People ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/epidemiology* ; Risk Factors ; Thrombosis/chemically induced* ; China/epidemiology* ; Anticoagulants/adverse effects* ; Recurrence

BACKGROUND: Liver biopsy for the diagnosis of non-alcoholic steatohepatitis (NASH) is limited by its inherent invasiveness and possible sampling errors. Some studies have shown that cytokeratin-18 (CK-18) concentrations may be useful in diagnosing NASH, but results across studies have been inconsistent. We aimed to identify the utility of CK-18 M30 concentrations as an alternative to liver biopsy for non-invasive identification of NASH. METHODS: Individual data were collected from 14 registry centers on patients with biopsy-proven non-alcoholic fatty liver disease (NAFLD), and in all patients, circulating CK-18 M30 levels were measured. Individuals with a NAFLD activity score (NAS) ≥5 with a score of ≥1 for each of steatosis, ballooning, and lobular inflammation were diagnosed as having definite NASH; individuals with a NAS ≤2 and no fibrosis were diagnosed as having non-alcoholic fatty liver (NAFL). RESULTS: A total of 2571 participants were screened, and 1008 (153 with NAFL and 855 with NASH) were finally enrolled. Median CK-18 M30 levels were higher in patients with NASH than in those with NAFL (mean difference 177 U/L; standardized mean difference [SMD]: 0.87 [0.69-1.04]). There was an interaction between CK-18 M30 levels and serum alanine aminotransferase, body mass index (BMI), and hypertension ( P  < 0.001, P  = 0.026 and P  = 0.049, respectively). CK-18 M30 levels were positively associated with histological NAS in most centers. The area under the receiver operating characteristics (AUROC) for NASH was 0.750 (95% confidence intervals: 0.714-0.787), and CK-18 M30 at Youden's index maximum was 275.7 U/L. Both sensitivity (55% [52%-59%]) and positive predictive value (59%) were not ideal. CONCLUSION This large multicenter registry study shows that CK-18 M30 measurement in isolation is of limited value for non-invasively diagnosing NASH.
Humans ; Non-alcoholic Fatty Liver Disease/diagnosis* ; Keratin-18 ; Biomarkers ; Biopsy ; Hepatocytes/pathology* ; Apoptosis ; Liver/pathology*

Objective:To introduce how to quickly set up a doctor team to achieve efficient treatment of batchs COVID-19 patients in Changchun GongTi shelter hospital.Methods:A cross-sectional study was conducted to analyze the basic situation of the doctors who supported the Changchun Gongti shelter hospital. The workload is the total number of patients from April 3 to 28, 2022. At the beginning of the task, the first week and the third week of the task, the five point scoring method was used to reflect the doctor's physical and mental state, stress state and rescue achievement. The time phased scheduling and disease grading management were fully implemented after 10 days of operation in the shelter. The doctors' ward round efficiency and self scoring changes before and after the implementation of the plan were compared, and the rescue results were summarized.Results:Total of 56 doctors (the Sichuan medical assistance team to Changchun), who undertook the work of Changchun Gongti shelter Hospital, came from 12 professional departments of 14 hospitals. By internal and external linkage-time phased scheduling and information-based patient zoning and grading management, the admission time of batch patients was shortened from (14.64±10.09) min to (6.80±5.10) min per person( P<0.05), the number of patients that each doctor can view per hour ranges from (28.50±12.26) to (68.43±19.95) ( P<0.01). A total of 1 293 patients were treated. There were no deaths, no accidents and no mild illness to severe illness in shelter hospital. 35 doctors completed a continuous survey. Before and after the implementation of those measures, the average physical state scores and the psychological state scores of doctors improved ( P=0.03), the self-score of stress feeling decreased ( P<0.01), and the self-score of professional achievement increased ( P<0.01). Conclusions:To adapt to the characteristics of emergency treatment for batch COVID-19 patients, the internal and external linkage-time phased scheduling and information-based patient zoning and grading management could help the temporarily convened doctors deal with a large number of patients efficiently, reduce work stress and exposure risk in shelter hospital.

Objective To understand the situation and the influencing factors of life quality in diabetic patients in Shanghai， and to develop effective intervention measures. Methods A total of 212 diabetic patients in Baoshan District， Shanghai were selected as the research objects. Diabetes specific quality of life scale （DSQL） was used to investigate the basic situation and quality of life of patients. Combined with biochemical detection indexes and questionnaire survey， data were analyzed by variance analysis and multiple linear stepwise regression analysis. Blood glucose level was assessed according to the 1999 WHO diagnostic criteria for type 2 diabetes. Results The overall quality of life score in the patients was 4.31±7.82， which was higher than the domestic norm. The best quality of life was in the dimension of physiological function with the score of 1.84±6.00， which was lower than the domestic norm. The next was the dimension of social relationship， and the worst was the dimension of treatment. The single factor analysis and multivariate analysis identified the following influence factors of quality of life in the patients： family history， educational level， exercise habit， blood glucose control and diet control. There was a negative correlation with educational level and blood glucose control， and a positive correlation with diet control. Conclusion The quality of life in the middle-aged diabetic patients was affected by the education level， blood glucose control and diet control. We suggest to strengthen the community management， health education， and improve the living habits.

Objective: To evaluate the efficacy and safety of ombitasvir/paritaprevir/ritonavir (OBV/PTV/r) 25/150/100 mg once daily and dasabuvir (DSV) 250 mg twice daily combined with ribavirin in adult patients of Mainland China with chronic HCV genotype 1b infection and compensated cirrhosis. Methods: An open-label, multicenter, phase 3 clinical trial study was conducted in mainland China, Taiwan, and South Korea. Adult patients with compensated cirrhosis (Metavir score =F4) who were newly diagnosed and treated for hepatitis C virus genotype 1b infection with ombitasvir/paritaprevir/ritonavir and dasabuvir combined with ribavirin for 12 weeks were included. Assessed SVR rate of patients obtained at 12 and 24 weeks after drug withdrawal. Efficacy and safety were evaluated in patients who received at least one time study drugs. Results: A total of 63 patients from mainland China were enrolled, 62 of whom (98.4%) had a baseline Child-Pugh score of 5 points. The overall rate of SVR12 and SVR24 in patients was 100% (95% CI: 94.3% to 100.0%). Most of the adverse events that occurred were mild. The incidence of common (≥10%) adverse events and laboratory abnormalities included elevated total bilirubin (36.5%), weakness (19.0%), elevated unconjugated bilirubin (19.0%) and conjugated bilirubin (17.5%), and anemia (14.3%). Three cases (4.8%) of patients experienced Grade ≥ 3 adverse events that were considered by the investigators to be unrelated to the study drug. None patients had adverse events leading to premature drug withdrawal. Conclusion Mainland Chinese patients with chronic HCV genotype 1b infection and compensated cirrhosis who were treated with OBV/PTV/r plus DSV combined with RBV for 12 weeks achieved 100 % SVR at 12 and 24 weeks after drug withdrawal. Tolerability and safety were good, and majority of adverse events were mild.

OBJECTIVE: To study the predictive value of transluminal attenuation gradient (TAG) derived from diastolic phase of coronary computed tomography angiography (CCTA) for identifying systolic compression of myocardial bridge (MB). MATERIALS AND METHODS: Consecutive patients diagnosed with MB based on CCTA findings and without obstructive coronary artery disease were retrospectively enrolled. In total, 143 patients with 144 MBs were included in the study. Patients were classified into three groups: without systolic compression, with systolic compression < 50%, and with systolic compression ≥ 50%. TAG was defined as the linear regression coefficient between intraluminal attenuation in Hounsfield units (HU) and length from the vessel ostium. Other indices such as the length and depth of the MB were also recorded. RESULTS: TAG was the lowest in MB patients with systolic compression ≥ 50% (−19.9 ± 8.7 HU/10 mm). Receiver operating characteristic curve analysis was performed to determine the optimal cutoff values for identifying systolic compression ≥ 50%. The result indicated an optimal cutoff value of TAG as −18.8 HU/10 mm (area under curve = 0.778, p < 0.001), which yielded higher sensitivity, specificity, positive predictive value, negative predictive value, and diagnostic accuracy (54.1, 80.5, 72.8, and 75.0%, respectively). In addition, the TAG of MB with diastolic compression was significantly lower than the TAG of MB without diastolic compression (−21.4 ± 4.8 HU/10 mm vs. −12.7 ± 8 HU/10 mm, p < 0.001). CONCLUSION: TAG was a better predictor of MB with systolic compression ≥ 50%, compared to the length or depth of the MB. The TAG of MB with persistent diastolic compression was significantly lower than the TAG without diastolic compression.
Angiography ; Coronary Artery Disease ; Humans ; Linear Models ; Myocardial Ischemia ; Retrospective Studies ; ROC Curve ; Sensitivity and Specificity

Objective To reversing methicillin-resistant Staphylococcus(MRS) to methicillin-susceptible Staphylococcus(MSS) by changing nutritional conditions and continuous transfer of culture .Methods MRS trains separating from clinical specimens were cultured in different conditions ,continuous cultural transfer ,and drug sensitive test were proceeded periodically to observe the phe-notypic and chemical reaction change of MRS .The mecA gene were detected of the original and mutant strains by polymerase chain reaction(PCR) ,then the gene sequenced and compared .Results 53 MRS strains were studied .6 strains were phenotype successful-ly converted to MSS in different cultural conditions ,among them mecA gene was undetected in 2 strains ,and down expressed in 4 strains .Conclusion The MRS strains separated from clinical specimens may revert to MSS by culture under different nutritional conditions .The mecA gene of MRS may be lost or lower expressed and the MRS and mutant strains may be different in genomics .

AIM:To generate monoclonal antibodies against human augmenter of liver regeneration (rhALR). METHODS:After BALB/C mice were immunized by the purified rhALR, the cells of spleen were fused with the cells of SP2/0; The titer and speciality were respectively fathomed from ascites or foster fluid by ELISA and Western-blot test. RESULTS:2 hybridoma cell lines were successfully obtained. The McAbs titer from ascites and foster fluid are respectively about 10-3-10-5 and 10-2-10-3. It is evident that the two McAbs were directed at different epitopes. CONCLUSIONS:The McAbs have higher speciality. It is significantly useful of the value that how hALR distribute in tissue organs, how the hALR signals the metabolism in the body and the control distribution of the hALR on cell growth on the translational level and so on is researched.

AIM: To screen the proteins interacting with human augmenter of liver regeneration (hALR) by yeast two-hybrid system and to study the mechanism of hALR action. METHODS: hALR bait plasmid was constructed by ligating the gene of hALR into pGBKT7, then transformed into yeast AH109. The yeast strain AH109 containing pGBKT7-hALR was mated with yeast Y187 containing human liver cDNA library plasmid. Diploid yeast was plated on SD/-trp-leu-his-ade (QDO) for screening and on QDO containing X-?-gal for further selection.The AD/library inserts were amplified by PCR and the PCR products were characterized by digesting with Sau3AⅠ and HaeⅢ restriction enzyme to eliminate the duplicates. After sequencing, the positive clones were analysed by bioinformatics. RESULTS: Several positive clones were obtaind. The sequencing and analysis shown that one of them is 669 bp DNA fragment encoding ? subunit of Na +,K +-ATPase. The 224 bp 3′terminal DNA fragment is non-encoder region, and the 445 bp 5′terminal DNA encodes C-terminal 147 amino acid residues of Na +, K +-ATPase ? subunit. CONCLUSION: The results of screening proteins using yeast two-hybrid system showed that hALR could interact directly with Na +, K +-ATPase in the yeast cell.