[Objective] To establish a method for detecting the potency of recombinant human coagulation factor Ⅶa for injection. [Methods] By adding the sample and factor Ⅶ deficient plasma to the sample cup and activating the reaction with prothrombin time assay reagent (PT reagent), the coagulation time of the sample was determined by the change in magnetic bead swing amplitude in the sample cup. The logarithm of coagulation time was inversely proportional to the logarithm of human factor Ⅶa potency. [Results] Under the experimental conditions, the specificity of the methodology was evaluated through spiked recovery, and the recovery rates ranged from 90.0% to 110.0%. Within the range from 0.125 to 1.000 IU/mL, there was a good linear response between the potency and coagulation time of the standard and sample, with correlation coefficients r>0.99. As for the accuracy and repeatability, the recovery rates of various concentrations detected in the stock solution were 101.0%, 100.0% and 112.0%, respectively, with RSD values of 2.6%, 4.0% and 0.0%, respectively. The recovery rates of various concentrations in finished product testing were 104.0%, 94.7% and 112.0%, respectively, with RSD values of 1.9%, 2.4% and 0.0%, respectively. As for the intermediate precision, the RSD were 4.5% and 3.7%, respectively. After treated with sample diluent, the sample was tested at room temperature for 6 hours and still exhibited relatively stable biological activity. [Conclusion] This detection method is accurate, stable, easy to operate and highly automated, and is suitable for detecting the potency of recombinant human coagulation factor Ⅶa for Injection.

OBJECTIVE To systematically summarize the working model of pharmacy consultation in medical institutions in China， and to provide reference for the normalization of process， standardization of content and homogenization of services of pharmacy consultation. METHODS A systematic search of Chinese and English literature databases was conducted to incorporate the literature on the working model of pharmacy consultation published by medical institutions in China. Two researchers screened and extracted the key information， and ultimately conducted qualitative summary and descriptive analysis. RESULTS Based on the included 11 articles， the pharmacy consultation working models were explored by clinical pharmacists in China. The contents of consultation mainly involved anti-infection， parenteral nutrition， cancer pain， etc. The general concept of pharmacy consultation should refer to the constructed flowchart， specific consultation problems could refer to the pathway， mind map， or decision tree and other framework guidance to carry out the work. Finally， consultation opinions could be written according to the consultation system or specialty consultation templates， and the adoption of a new working model （such as pharmacist active consultation） could also promote the number and acceptance rate of pharmacy consultation. CONCLUSIONS A series of working models of pharmacy consultation have been initially explored in medical institutions in China. However， it is not yet perfect and lacks a unified quality control and evaluation system for pharmacy consultation， which should be the focus of future research and practice.

【Objective】 To analyze the influence of plasma donation on human total protein level and the impact of different blood collection tubes on total protein level detection. 【Methods】 A total of 1 373 plasma donors from 11 apheresis plasma stations in 6 provinces/autonomous regions from March to April, 2021 were selected. Whole blood was collected by ordinary blood collection tube without anticoagulant, heparin anticoagulant tube and sodium citrate anticoagulant tube, and then respectively divided into serum group, heparin anticoagulant group, and sodium citrate anticoagulant group. After separating serum and plasma, the samples were subjected to total protein detection using the biuret method. Kruskal-Wallis test was used to compare the total protein levels among different tubes. The plasma donors were divided into male group (n=597) and female group (n=776), and the total protein levels between different genders were compared by t test. The plasma donors were divided into Sichuan group, Hubei group and Gansu group according to the region, and the Games-Howell test was used for comparison. 【Results】 The median serum total protein level of 1 373 donors was 73.1g/L, which was consistent with the reference range of 65-85 g/L. The median total protein levels of the serum group, heparin anticoagulant group and sodium citrate anticoagulant group were 73.1g/L, 73.3g/L and 63.8g/L, respectively, with statistically significant difference (P<0.05). There was statistical significance in total protein level between sodium citrate anticoagulant group and serum group, sodium citrate anticoagulant group and heparin anticoagulant group(P<0.05), but no statistical significance was noticed between serum group and heparin anticoagulant group (P> 0.05). The serum total protein levels of male group and female group were (72.41±5.40)g/L and (73.67±4.95)g/L, reseectively, and the difference was statistically significant (P<0.05). The serum total protein level in Sichuan group, Hubei group and Gansu group was (73.91±4.29)g/L, (74.17±5.11)g/L and (67.09±3.65)g/L, respectively (P<0.05).The difference between Gansu group and Hubei group, Gansu group and Sichuan group was statistically significant (P<0.05), but no significant difference was noticed between Sichuan group and Hubei group (P>0.05). 【Conclusion】 Plasma donors who meet the donation criteria will not experience abnormal total protein levels due to regular plasma donation. There were differences in total protein levels among different blood collection tubes, different genders and different regions. The total protein level of females was higher than that of males. The total protein level was the highest in Hubei province, followed by Sichuan and Gansu.Heparin anticoagulant group was the highest, followed by serum group and sodium citrate anticoagulant group.

The development of acute liver injury can result in liver cirrhosis, liver failure, and even liver cancer, yet there is currently no effective therapy for it. The purpose of this study was to investigate the protective effect and therapeutic mechanism of Lyciumbarbarum polysaccharides (LBPs) on acute liver injury induced by carbon tetrachloride (CCl₄). To create a model of acute liver injury, experimental canines received an intraperitoneal injection of 1 mL/kg of CCl₄ solution. The experimental canines in the therapy group were then fed LBPs (20 mg/kg). CCl₄-induced liver structural damage, excessive fibrosis, and reduced mitochondrial density were all improved by LBPs, according to microstructure data. By suppressing Kelch-like epichlorohydrin (ECH)-associated protein 1 (Keap1), promoting the production of sequestosome 1 (SQSTM1)/p62, nuclear factor erythroid 2-related factor 2 (Nrf2), and phase II detoxification genes and proteins downstream of Nrf2, and restoring the activity of anti-oxidant enzymes like catalase (CAT), LBPs can restore and increase the antioxidant capacity of liver. To lessen mitochondrial damage, LBPs can also enhance mitochondrial respiration, raise tissue adenosine triphosphate (ATP) levels, and reactivate the respiratory chain complexes I‒V. According to serum metabolomics, the therapeutic impact of LBPs on acute liver damage is accomplished mostly by controlling the pathways to lipid metabolism. 9-Hydroxyoctadecadienoic acid (9-HODE), lysophosphatidylcholine (LysoPC/LPC), and phosphatidylethanolamine (PE) may be potential indicators of acute liver injury. This study confirmed that LBPs, an effective hepatoprotective drug, may cure acute liver injury by lowering oxidative stress, repairing mitochondrial damage, and regulating metabolic pathways.
Animals ; Dogs ; Antioxidants/metabolism* ; Carbon Tetrachloride ; Chemical and Drug Induced Liver Injury/drug therapy* ; Kelch-Like ECH-Associated Protein 1/metabolism* ; Liver ; Metabolic Networks and Pathways ; Mitochondria/metabolism* ; NF-E2-Related Factor 2/metabolism* ; Oxidative Stress ; Polysaccharides/pharmacology* ; Lycium/chemistry*

Objective:To investigate the clinical characteristics and prognosis of cryptococcal meningitis patients with anti-granulocyte-macrophage colony-stimulating factor (GM-CSF) autoantibodies.Methods:A total of 216 non-acquired immunodeficiency syndrome (AIDS) related cryptococcal meningitis cases with positive cultures of Cryptococcus, hospitalized at Huashan Hospital, Fudan University during January 2014 and December 2021, were retrospectively included. The serum anti-GM-CSF autoantibodies were detected by enzyme linked immunosorbent assay, and the clinical characteristics and prognosis were compared between patients with and without anti-GM-CSF autoantibodies. Statistical comparisons were mainly performed using the chi-square test or Fisher′s exact test. Cox proportional-hazards model was used to analyze the risk factors associated with prognosis. Results:Among 216 enrolled patients, 23 patients were positive of anti-GM-CSF autoantibodies, with a positive rate of 10.6%. Among 23 patients, seven cases were infected with Cryptococcus gattii, and 16 cases were infected with Cryptococcus neoformans. In the group with positive anti-GM-CSF autoantibodies, 30.4%(7/23) of the patients were infected with Cryptococcus gattii, which was higher than that of 1.6%(3/193) in the group with negative anti-GM-CSF autoantibodies, and the difference was statistically significant ( χ2=38.82, P<0.001). In the group with positive anti-GM-CSF autoantibodies, 30.0% (6/20) had mass lesions with a diameter greater than three centimeters in the lungs, and the one-year all-cause mortality rate was 50.0% (10/20), which were both higher than those of 3.4%(5/145) and 16.1% (29/180) in the negative group, respectively. The differences were both statistically significant (both Fisher′s exact test, P<0.01). Age≥60 years (hazard ratio ( HR)=4.146, P=0.002), predisposing factors ( HR=3.160, P=0.021), epilepsy ( HR=6.129, P=0.002), positive anti-GM-CSF autoantibodies ( HR=2.675, P=0.034), white blood cell count of cerebrospinal fluid (CSF)<100 ×10 6/L ( HR=2.736, P=0.039), the titers of cryptococcal capsular polysaccharide antigen of CSF≥1∶1 280 ( HR=4.361, P=0.009) were independent risk factors for one-year all-cause mortality in patients with cryptococcal meningitis. Conclusions:In non-AIDS related cryptococcal meningitis patients, the positive rate of serum anti-GM-CSF autoantibodies is as high as 10.6%. Patients with anti-GM-CSF autoantibodies could be infected with both Cryptococcus neoformans and Cryptococcus gattii, and they have higher proportion of lung mass lesions than patients with negative anti-GM-CSF autoantibodies. The one-year survival rate decreases significantly in patients with anti-GM-CSF autoantibodies, which is an independent risk factor for the prognosis of cryptococcal meningitis.

In order to standardize the review and comment of national key monitoring drug prescriptions （medical orders） by medical institutions at all levels， the Sichuan Academy of Medical Sciences·Sichuan Provincial People’s Hospital took the lead in compiling the Review and Comment Rules of National Key Monitoring Drugs prescriptions （Medical Orders） herein after referred to as the Rules in accordance with the Second Batch of National Key Monitoring Rational Drug Use List （hereinafter referred to as the List） issued by the National Health Commission confirmed in Jan. 13， 2023. According to the laws and drug instructions issued by the national drug regulatory department， clinical guidelines and expert consensus， combined with the actual situation of patients （including age， body weight， liver and kidney function）， the writing group classified the common and unreasonable drug use problems for 30 kinds of drugs included in the List and develop the review and comment details. After two rounds of Delphi method questionnaire research and experts’ online meetings， and reviewed by the steering committee， the final Rules was formed. The Rules aim to provide reference for the evaluation of the rational use of drugs included in the List by medical institutions， so as to realize the standardized management of key monitoring drugs， promote the rational drug use in medical institutions， and ensure the safety of drug use for patients.

【Objective】 To determine the ELISA kit for screening convalescence plasma with high potency of SARS-CoV-2 IgG by comparing and analyzing the plasma detection results of convalescent plasma collected in different periods via ELISA kits from two manufacturers and the results of mixed plasma with different potency via pseudovirus neutralization experiments. 【Methods】 Two ELISA kits from different manufacturers(named A, B) were used to detect the plasma of 269 convalescent patients collected from Feb.2020~Jan.2022. The correlation and concordance rate of the two results were analyzed to determine the kit preliminarily. According to the titers of diluted series of standard of the preliminary selected kit, 5 mixed plasma samples (G4-G128) with different potency were prepared. The correlation of ELISA IgG results of product A/B, as well as the pseudovirus neutralization test of the original strain, Omicron mutant BA.1 and BA.2 strains were analyzed. Combined with the outside-well dilution mode of the strongly positive samples, the kit for high potency of SARS-CoV-2 IgG screening was determined. 【Results】 When the internal control reference B2 was used as the standard, the detection sensitivity of product A and B was 1∶32 vs 1∶8; the detection sensitivity of product A was 4 times that of product B. The correlation Pearson r between the results given by two kits was 0.944 1(P<0.000 1). Product B with low sensitivity was primarily selected as an alternative kit. The ELISA IgG results of samples from mixed plasma showed that the order of correlation r between product A and B was 0.988. The correlation r between product A and neutralization antibody potency of the three viruses was original strain (0.978)>BA.2(0.970)>BA.1(0.799); the order of correlation r between ELISA IgG results of product B and neutralization antibody potency of the three viruses was original strain(0.994)>BA.2(0.968)>BA.1(0.804). If twice-diluted B2 was taken as the excellent standard, 55.4% of product B met the criterion, while 47.2% of product A met.For positive plasma with high IgG potency, the product B kit required a lower dilution of the sample, which was more convenient to operate. 【Conclusion】 Both of the ELISA IgG kit from product A and B can be used to screen IgG antibodies of SARS-CoV-2, while product B is more suitable for screening positive plasma with high IgG potency.

The development of acute liver injury can result in liver cirrhosis, liver failure, and even liver cancer, yet there is currently no effective therapy for it. The purpose of this study was to investigate the protective effect and therapeutic mechanism of Lycium barbarum polysaccharides (LBPs) on acute liver injury induced by carbon tetrachloride (CCl4). To create a model of acute liver injury, experimental canines received an intraperitoneal injection of 1 mL/kg of CCl4 solution. The experimental canines in the therapy group were then fed LBPs (20 mg/kg). CCl4-induced liver structural damage, excessive fibrosis, and reduced mitochondrial density were all improved by LBPs, according to microstructure data. By suppressing Kelch-like epichlorohydrin (ECH)-associated protein 1 (Keap1), promoting the production of sequestosome 1 (SQSTM1)/p62, nuclear factor erythroid 2-related factor 2 (Nrf2), and phase Ⅱ detoxification genes and proteins downstream of Nrf2, and restoring the activity of anti-oxidant enzymes like catalase (CAT), LBPs can restore and increase the antioxidant capacity of liver. To lessen mitochondrial damage, LBPs can also enhance mitochondrial respiration, raise tissue adenosine triphosphate (ATP) levels, and reactivate the respiratory chain complexes I?V. According to serum metabolomics, the therapeutic impact of LBPs on acute liver damage is accomplished mostly by controlling the pathways to lipid metabolism. 9-Hydroxyoctadecadienoic acid (9-HODE), lysophosphatidylcholine (LysoPC/LPC), and phosphatidylethanolamine (PE) may be potential indicators of acute liver injury. This study confirmed that LBPs, an effective hepatoprotective drug, may cure acute liver injury by lowering oxidative stress, repairing mitochondrial damage, and regulating metabolic pathways.

Objective To investigate the efficacy of entecavir (ETV) versus tenofovir disoproxil fumarate (TDF) and the treatment measures for poor response in previously untreated chronic hepatitis B (CHB) patients with high viral load. Methods A total of 165 CHB patients who received antiviral therapy and met the inclusion criteria in Department of Infectious Diseases, The First Affiliated Hospital of Guangxi Medical University, from June 2016 to July 2021 were enrolled. The patients enrolled had a baseline HBV DNA level of > 6lg copies/ml and were previously untreated CHB patients who had used ETV or TDF for 48 weeks, and quantitative real-time PCR was used to measure HBV DNA. Virologic response rate was calculated after 48 weeks of treatment; a logistic regression analysis was used to investigate the influencing factors for the response of HBV DNA < 500 copies/mL and HBV DNA < 100 copies /mL at 48 weeks; a stratified analysis was performed to compare the virologic response rate of HBV DNA < 500 copies /ml and HBV DNA < 100 copies/ml after 48 weeks between the patients with different ages, sexes, baseline HBV DNA levels, baseline alanine aminotransferase (ALT) levels, types of first-line medication, and HBeAg statuses. The Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups, the chi-square test or the Fisher's exact test was used for comparison of categorical data between two groups, and the binary logistic regression model was used for multivariate analysis. Results After 48 weeks of treatment, 85.5% (141/165) of the patients achieved an HBV DNA load of < 500 copies/mL, and 66.1% (109/165) of the patients achieved an HBV DNA load of < 100 copies /mL, with no significant difference in treatment outcome between the ETV group and the TDF group. The multivariate logistic regression analysis showed that sex( OR =2.793, 95% CI : 1.197-6.517), baseline HBV DNA( OR =0.369, 95% CI : 0.142-0.959), baseline ALT( OR =4.556, 95% CI : 1.770-11.732), and baseline HBeAg( OR =0.120, 95% CI : 0.033-0.429) were influencing factors for complete virologic response(all P < 0.05). For the patients with normal ALT (≤40 U/L) at baseline, 75.6% (34/45) achieved an HBV DNA load of < 500 copies/mL after 48 weeks of treatment, and 53.3% (24/45) achieved an HBV DNA load of < 100 copies/mL, with no significant difference in treatment outcome between the ETV group and the TDF group. For the patients with abnormal ALT (> 40 U/L) at baseline, 89.2% (107/120) achieved an HBV DNA load of < 500 copies/mL after 48 weeks of treatment, and the proportion of such patients in the TDF group was significantly higher than that in the ETV group (96.1% vs 84.1%, χ 2 =4.386, P =0.036); 70.8% (85/120) achieved an HBV DNA load of < 100 copies/mL, the proportion of such patients was no significant difference between the TDF group and the ETV group (78.4% vs 65.2%). The response of HBV DNA < 100 copies/ml of the normal baseline ALT group and the abnormal baseline ALT group, there were no significant differences between the patients aged≤30 years and aged > 30 years (77.8% vs 47.2%, 85.2% vs 66.7%). For the patients who did not achieve complete virologic response (HBV DNA ≥100 copies/mL) after 48 weeks of treatment, 87.9% (29/33) achieved complete virologic response after the original treatment regimen was prolonged for 48 weeks, and 100% (9/9) of the patients achieved complete virologic response after switching to or adding the first-line nucleos(t)ide analogues (NUCs) without cross-resistance sites with the original regimen for another 48 weeks. Conclusion The patients aged > 30 years should receive antiviral therapy as early as possible, regardless of viral load and ALT level, especially those with a family history of liver cirrhosis or hepatocellular carcinoma; the patients aged ≤30 years who have a normal ALT level and a high viral load should consider initiating antiviral therapy after providing informed consent. For the patients with poor response after 48 weeks of treatment, first-line NUCs without cross-resistance sites with the original regimen should be switched to or added in time.

OBJECTIVE To mine the signals of adverse dr ug events （ADE）for tolvaptan based on FAERS database ，and to provide reference for safe use of drugs in clinic. METHODS The data of tolvaptan-induced ADE were collected from FAERS database during the first quarter of 2004 to the third quarter of 2020；the reporting odds ratio （ROR）method and the proportional reporting ratio （PRR）method of disproportional method were used for data mining. RESULTS A total of 4 744 ADE reports of the target drug tolvaptan were extracted ，involving 1 279 ADEs. The reporting countries were mainly the United States and Japan ，etc. A total of 199 ADE signals were obtained ，involving 21 system organ classes （SOCs），which mainly focused on various examinations（n＝56），hepatobiliary disorders （n＝17），renal and urinary disorders （n＝14），etc. Among them ，80 signals were not mentioned in existing instructions for tolvaptan in China ，such as decreased glomerular filtration rate ，positional vertigo ， rupture of renal cyst ，renal cyst infection ，pulmonary malignant tumor. CONCLUSIONS Before using tolvaptan ，drug evaluation should be performed well ，especially the patients with basic diseases such as heart failure ，liver insufficiency and renal insufficiency. During treatment ，the indexes of liver function and renal function should be closely monitored ；timely intervention measures should be taken to avoid related injury and disease deterioration caused by ADE when ADE or disease progression occurs.