Liquid chromatography-tandem mass spectrometry (LC-MS/MS) technology has the characteristics of high specificity and high throughput, making it rapidly applied and developed in the field of clinical testing. Its application in the monitoring of therapeutic drugs can effectively improve the quantitative accuracy and sensitivity, and formulate a personalized and optimal dosing plan for patients. However, this technology still faces some challenges, and automation, quality control, and quantitative traceability will be the future development direction.

Objective: To design the proficiency testing (PT) project (No. NIFDC-PT-183) for assays of bismuth potassium citrate capsules and organize to assess the proficiency of complexometric titration in laboratories, and provide some technical analyses and advices.
Methods: Two groups of samples with different concentration were prepared. The uniformity was evaluated with one-way analysis of variance and the stability was confirmed with t-test, whose results all conformed the requirements. The samples with three combinations were randomly distributed to 279 laboratories. The determination was performed according to the assays of bismuth potassium citrate capsules in Volume Ⅱ of the Chinese Pharmacopoeia 2015. The median value and normalized interquartile range (NIQR) of robust statistical analysis was adopted and Z-scores were used to evaluate the results from each of laboratories.
Results: Among 279 laboratories, 240 laboratories results were satisfactory, 23 were questionable, and the other 16 were unsatisfied. The satisfaction rate was 86.0%.
Conclusion: The overall capacity of national laboratories for assays of bismuth potassium citrate capsules is good while a portion of participants require further improvement.

Objective To carry out a proficiency testing of content determination of geniposide in Gardeniae fructus,evaluate the content determination ability of index components in traditional Chinese medicine in the laboratory of inspection and detection in drug-related fields,and improve the quality control ability of content determination of related laboratories.Methods The laboratory's capability-verification activities were conducted based on the CNAS-RL02 Rules for Proficiency Testing and ISO/IEC 17043 Conformity Assessment-General Requirements for Proficiency Testing.After preparing the sample,the results of homogeneity and stability tests were analyzed according to CNAS-GL003 Guidance on Evaluating the Homogeneity and Stability of Samples Used for Proficiency Testing.After the test results were qualified,they were used as proficiency testing samples and randomly distributed to participants.The results were collected,and the robust statistical method and the Z scores were used to analyze the results of these laboratories'reports.Results 403 laboratories in this proficiency testing program reported the results,of which 367 results were acceptable,accounting for 91.07％,17(4.22％)laboratories obtained suspicious results,and 19 laboratories gave unsatisfactory results,with the dissatisfaction rate of 4.71％.Conclusion The majority of the 403 participant laboratories have the ability to determine the content of geniposide in Gardeniae fructus by HPLC and the laboratory testing ability and quality management level of the drug monitoring system are high.This proficiency testing provides a basis for understanding the technical reserve capacity and management level of China's pharmaceutical inspection and testing laboratories,and provides technical support for future government supervision.

Objective:To study the expression of peripheral blood NKT-like cells in patients with systemic sclerosis (SSc), to explore the correlation between NKT-like cells and laboratory and clinical indicators of systemic sclerosis, and investigate the role of NKT-like cells in the occurrence and development of Systemic sclerosis.Methods:Forty-six SSc patients (SSc group) were enrolled from Department of Rheumatology and Immunology of Peking University People 's Hospital during December 2018 to December 2019. Thirty healthy subjects with matched age and sex were selected as healthy control group (HC group). The cell count and percentage of NKT-like cells and other lymphocyte subsets in peripheral blood were detected by flow cytometry. At the same time, other laboratory indexes were determined by different methods. Spearman's correlation analysis, Pearson's correlation analysis, Man-Whitney U test and Fisher's exact test were used to analyze the difference and correlation between NKT-like cells and other clinical and laboratory indicators. Results:Compared with HC group [165(72, 226)cells/μl], the cell count of NKT-like cells in peripheral blood of SSc group[30(19, 58)cells/μl] was significantly decreased ( Z=-5.69, P<0.001). Correlation analysis showed that the cell count of NKT-like cells was positively correlated with total T lymphocytes ( r=0.56, P<0.001), CD4 +T cells ( r=0.42, P=0.004), CD8 +T cells ( r=0.60, P<0.001), B cells ( r=0.50, P<0.001) and NK cells ( r=0.33, P=0.024), respectively. The percentage of NKT-like cells in lymphocytes was also positively correlated with the percentage of CD8 +T cells ( r=0.34, P=0.020), but not significantly correlated with other subset of lymphocytes. The ESR of the NKT-like cell decreased group was significantly higher than that of the NKT-like normal group[15(9, 28) mm/1 h vs 8 (4, 16) mm/1 h, Z=-2.04, P=0.042]. Moreover, the cell count of NKT-like cells was negatively correlated with ESR ( r=-0.34, P=0.019). Conclusion:The cell count and percentage of NKT-like cells in peripheral blood of SSc patients decreased significantly. NKT-like cells were not only positively correlated with a variety of lymphocyte subpopulations, but also negatively correlated with ESR. NKT-like cells may be used as an indicator to monitor the disease activity in patients with SSc.

Objective: To examine the significance and prognostic value of the classification of hilar cholangiocarcinoma based on actual anatomical location. Methods: A retrospective study was conducted including 120 patients of hilar cholangiocarcinoma treated at the Second Affiliated Hospital,Zhejiang University School of Medicine and Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine from January 2019 to December 2021. Patients with hilar cholangiocarcinoma were classified for seven types according to the site of tumor location. The clinicopathological and prognostic data of 120 patients were retrospectively analyzed(There were 57 males and 63 females,the age (M(IQR)) was 61(22)years(range:42 to 85 years)). All patients received radical resection without visible intraoperative tumor residue and negative bile duct resection margin according to intraoperative pathological biopsy. The classification variables were analyzed by Pearson χ² test or Fisher's exact probability test,one-way ANOVA or Kruskal-Wallis rank sum test.Kaplan-Meier method was used for survival analysis. Cox proportional risk model was used for prognostic factors. Results: The coincidence rate of preoperative surgical planning and actual operational styles was verified in 33 cases. Twenty-six cases were consistent,and 7 cases were inconsistent,with a coincidence rate of 78.8%. According to the actual anatomical location,patients in type of secondary branch experienced a significantly longer operation duration,a higher portal vein resection rate,margin positive rate and more advanced T stage(all P<0.05). The median overall survival time of the unilateral main trunck group was 27.0 months,and the bilateral group was 17.0 months. Survival analysis based on the tumor classification of the actual anatomical location showed that the unilateral or main trunck group predicted less aggressive clinical features and favorable outcomes(HR=1.931,95%CI:1.066 to 3.499,P<0.05). Multivariate analysis demonstrated that the actual anatomical location of the tumor type(HR=2.269,95%CI:1.333 to 3.861,P=0.003),combined liver resection(HR=0.464,95%CI:0.253 to 0.848,P=0.013) and N stage(HR=6.317,95%CI:3.083 to 12.944,P<0.01) were independent factors affecting the prognosis of patients. Conclusion: The classification based on the actual anatomy can be used as a promising scheme in refining patient stratification and predicting survival in hilar cholangiocarcinoma,and it can guide the selection of surgical methods,and predict operative safety and radical resection rate.
Bile Duct Neoplasms/surgery* ; Bile Ducts, Intrahepatic/pathology* ; China ; Cholangiocarcinoma/surgery* ; Female ; Humans ; Klatskin Tumor/surgery* ; Male ; Retrospective Studies

Child ; Consensus ; Drugs, Chinese Herbal ; Humans ; Medicine, Chinese Traditional ; Respiratory System

The cold congeal and blood stasis syndrome is a common clinical traditional Chinese medicine（TCM） syndrome. The animal model of cold ongeal and blood stasis syndrome is the basis for exploring the essence of TCM cold congeal and blood stasis syndrome，and the premise of follow-up TCM clinical research.This paper summarized the preparation method， theoretical support，and evaluation method of animal models of cold congeal and blood stasis syndrome in recent years and analysed the strengthens and weaknesses of different models. At present，the common animal models of cold congeal and blood stasis syndrome mainly include etiological model，etiological and pathological composite model and disease-syndrome combination model. The etiological model was mainly prepared by cold exposure，which could be divided into whole-body freezing， ice bath and local frostbite. The etiological and pathological composite model was mainly prepared by cold stimulation combined with epinephrine injection. The common disease-syndrome combination models included the coronary heart disease model of cold congeal and blood stasis syndrome，primary dysmenorrhea model of cold congeal and blood stasis syndrome，endometriosis model of cold congeal and blood stasis syndrome， and arteriosclerosis obliterans model of cold congeal and blood stasis syndrome. The three models have both advantages and disadvantages. Specifically， the disease-syndrome combination model had the highest consistency with clinical practice and was more reliable and practical. However， the disease types of this model were specific，and the combination method of disease and syndrome was controversial. The evaluation indicators of the animal models of cold congeal and blood stasis syndrome focused on the characterization of the syndrome and the physico-chemical indicators related to blood flow，such as blood rheology，coagulation function and microcirculation. In addition， some scholars explored the evaluation indicators from the aspects of vasomotor function，endocrine and energy metabolism. The objectivity and specificity of the current model evaluation methods needed to be further improved. The research of animal model of cold congeal and blood stasis syndrome should be based on clinical practice and oriented by clinical demand. Only by establishing animal models that are highly consistent with the characteristics of clinical disease and syndrome can we better reveal the essence of cold congeal and blood stasis syndrome and promote the modernization of TCM.

This project aimed to explore the protective effect of ginsenoside Rg_1 on hypoxia/reoxygenation(H/R)-induced H9 c2 cardiomyocyte injury and its underlying signaling pathway. The H/R model of H9 c2 cardiomyocytes was established and then the cells were divided into different treatment groups. CCK-8(cell counting kit-8) was used to detect the activity of cardiomyocytes; Brdu assay was used to detect the proliferation of H9 c2 cells; the caspase-3 activity was tested, and then the protein expression was assessed by Western blot. Flow cytometry was used to evaluate the apoptosis level of cardiomyocytes. Ginsenoside Rg_1 inhibited H/R-induced cardiomyocyte apoptosis and caspase-3 activity, promoted nuclear transcription of nuclear factor erythroid-2 related factor 2(Nrf2), and enhanced the expression of the downstream heme oxygenase-1(HO-1). Ginsenoside Rg_1 could increase Nrf2 nuclear transcription and HO-1 expression with the increase of concentration(10, 20, 40, 60 μmol·L~(-1)). However, the protective effect of ginsenoside Rg_1 on cardiomyocytes was significantly weakened after the transfection of Nrf2-siRNA. Ginsenoside Rg_1 could protect cardiomyocytes by activating the Nrf2/HO-1 pathway.
Apoptosis ; Ginsenosides/pharmacology* ; Heme Oxygenase-1/genetics* ; Humans ; Hypoxia ; Myocytes, Cardiac ; NF-E2-Related Factor 2/genetics*

OBJECTIVE: To evaluate the capacity of laboratories participated in the proficiency testing (PT) of determination potassium in serum and improve the quality of testing, and put forward technical suggestions for unsatisfied laboratories. METHODS: According to the requirements of CNAS related documents, the homogeneity and stability of the real PT sample were evaluated by one-way ANOVA and t test, respectively. The values of real PT samples were assigned by reference method which was used in PT results assay. It is required that the deviation of value of real PT samples (code:2, 3, 5) between the measured value and the assigned value shall be within ±15.0%. The precision of values for all samples should not be greater than 3.0%. RESULTS: All the laboratories submitted valid data according to the requirements. Only one laboratory did not meet the requirements, and the satisfaction rate was 90.9%. CONCLUSIONS The ability of most of laboratories are accurate and reliable.
Drinking Water/analysis* ; Laboratories ; Laboratory Proficiency Testing ; Potassium

BACKGROUND: Shenyankangfu Tablet (SYKFT) is a Chinese patent medicine that has been used widely to decrease proteinuria and the progression of chronic kidney disease. OBJECTIVE: This trial compared the efficacy and safety of SYKFT, for the control of proteinuria in primary glomerulonephritis patients, against the standard drug, losartan potassium. DESIGN, SETTING, PARTICIPANTS AND INTERVENTION: This was a multicenter, double-blind, randomized, controlled clinical trial. Primary glomerulonephritis patients, aged 18-70 years, with blood pressure ≤ 140/90 mmHg, estimated glomerular filtration rate (eGFR) ≥ 45 mL/min per 1.73 m MAIN OUTCOME MEASURES: The primary outcome was change in the 24-hour proteinuria level, after 48 weeks of treatment. RESULTS: A total of 735 participants were enrolled. The percent decline of urine protein quantification in the SYKFT group after 48 weeks was 8.78% ± 2.56% (P = 0.006) more than that in the losartan 50 mg group, which was 0.51% ± 2.54% (P = 1.000) less than that in the losartan 100 mg group. Compared with the losartan potassium 50 mg group, the SYKFT plus losartan potassium 50 mg group had a 13.39% ± 2.49% (P < 0.001) greater reduction in urine protein level. Compared with the losartan potassium 100 mg group, the SYKFT plus losartan potassium 100 mg group had a 9.77% ± 2.52% (P = 0.001) greater reduction in urine protein. With a superiority threshold of 15%, neither was statistically significant. eGFR, serum creatinine and serum albumin from the baseline did not change statistically significant. The average change in TCM syndrome score between the patients who took SYKFT (-3.00 [-6.00, -2.00]) and who did not take SYKFT (-2.00 [-5.00, 0]) was statistically significant (P = 0.003). No obvious adverse reactions were observed in any group. CONCLUSION: SYKFT decreased the proteinuria and improved the TCM syndrome scores of primary glomerulonephritis patients, with no change in the rate of decrease in the eGFR. SYKFT plus losartan potassium therapy decreased proteinuria more than losartan potassium therapy alone. TRIAL REGISTRATION NUMBER NCT02063100 on ClinicalTrials.gov.