ObjectiveBased on ultra-high performance liquid chromatography-quadrupole-time-of-flight mass spectrometry（UPLC-Q-TOF-MS/MS）， network pharmacology and molecular docking techniques， to explore the pharmacodynamic material basis and mechanism of Renshen Wuweizi Tang in treating spleen-lung Qi deficiency syndrome. MethodsThe chemical components in the decoction of Renshen Wuweizi Tang were systematically characterized and identified by UPLC-Q-TOF-MS/MS， and network pharmacology was used to screen potential active ingredients， collect component targets and gene sets related to spleen-lung Qi deficiency syndrome， and obtain protein interaction relationships through STRING. Cytoscape 3.9.1 was used to construct a "formula-syndrome" association network and calculate topological feature values. Gene ontology（GO） function and Kyoto Encyclopedia of Genes and Genomes（KEGG） pathway enrichment analysis were performed on core genes to explore potential pharmacodynamic links， the average shortest path between the formula-drug target network and the pharmacodynamic link gene network was calculated to discover dominant pharmacodynamic links， and MCODE plugin was used to identify core gene clusters from the dominant pharmacodynamic links， which were validated using Gene Expression Omnibus（GEO）， and molecular docking was performed between key components and core targets. ResultsOne hundred and thirty-seven components were identified in the negative ion mode， and eighty components were identified in the positive ion mode. After deduplication， a total of 185 components were identified， mainly composed of triterpenoid saponins（49） and flavonoids（54）. Based on the "formula-syndrome" correlation network analysis， energy metabolism was determined to be the dominant pharmacodynamic link of Renshen Wuweizi Tang in the treatment of spleen-lung Qi deficiency syndrome. The results of molecular docking showed that 7 components（adenosine， atractylenolide Ⅱ， atractylenolide Ⅲ， ginsenoside Rg₁， glycyrrhizin B₂， glycyrrhizin E₂ and campesterol） from 4 medicinal materials（Ginseng Radix et Rhizoma， Atractylodis Macrocephalae Rhizoma， Glycyrrhizae Radix et Rhizoma and Poria） in this formula might regulate energy metabolism by acting on 6 targets， namely cyclic adenosine monophosphate-response element binding protein 1（CREB1）， glyceraldehyde-3-phosphate dehydrogenase（GAPDH）， interleukin（IL）-6， nuclear transcription factor（NF）-κB1， peroxisome proliferator-activated receptor α（PPARα）， and tumor necrosis factor（TNF）， thus improving the symptoms of diseases related to spleen-lung Qi deficiency syndrome. ConclusionThis study established a UPLC-Q-TOF-MS/MS for rapid characterization and identification of chemical components in the decoction of Renshen Wuweizi Tang， expanding the understanding of the material composition of this formula， and found that 7 components might act on the key advantageous pharmacodynamic link "energy metabolism" through 6 targets to improve the related symptoms of spleen-lung Qi deficiency syndrome. This can provide a reference for the subsequent exploration of the material benchmark and mechanism of the famous classical formula.

OBJECTIVE To develop a population pharmacokinetic （PPK） model for mycophenolate mofetil active metabolite mycophenolic acid （MPA） in children with primary IgA nephropathy， explore the factors affecting the pharmacokinetic parameters of MPA， and provide a basis for clinical individualized therapy. METHODS Retrospective collection was conducted on 636 concentrations and clinical data from 47 pediatric patients with primary IgA nephropathy. PPK analysis was carried out by using the nonlinear mixed-effects model； the covariates were tested with a stepwise method. Goodness-of-fit plots， Bootstrap and visual predictive check were employed to evaluate the final model. RESULTS The pharmacokinetics of MPA in children with IgA nephropathy in vivo conformed to the first-order absorption and elimination two-compartment model （objective function value of 3 276.31）. Covariate analysis suggested that body weight and albumin （ALB） levels were significant influencing factors on apparent clearance rate and apparent distribution volume. The typical values of PPK parameters of MPA in the final model were as follows： the central room had a distributed volume of 5.79 L， the clearance rate was 4.06 L/h， the volume of peripheral ventricular distribution was 430.93 L， the clearance rate between compartments was 15.40 L/h， the oral absorption rate constant was 1.29 h－1. After verification， most of the predicted corrected observed concentration points were within the 90% confidence interval of the predicted corrected simulated concentration， indicating that the MPA final model had good predictive performance. CONCLUSIONS The PPK model of MPA in children with primary IgA nephropathy is established in this study， identifying body weight and ALB levels are significant factors affecting MPA metabolism.

Objective To investigate the effect of rutin on pyroptosis of nucleus pulposus cells in rats with intervertebral disc degeneration and its mechanism at cellular level.Methods Rat interdisc nucleus pulposus cells were randomly divided into control group,model group[interleukin-1β(IL-1β)induction],experiment-L group(25 μmol·L-1 rutin+10 ng·mL-1 IL-1β),experiment-M group(50 μmol·L-1 rutin+10ng·mL-1IL-1β),experiment-H group(100 μmol·L-1 rutin+10 ng·mL-1 IL-1 β),experiment-H+SRT1720 agonist group[100 μmol·L-1 rutin+10 ng·mL-1 IL-1 β+1 μmol·L-1 silent information regulator 1(SIRT1)agonist SRT1720].Real-time quantitative polymerase chain reaction(RT-qPCR)assay and Western blot assay were used to detect the expression of related genes and proteins;cell count kit-8(CCK-8)assay and enzyme-linked immunosorbent assay were used to detect the expression of cell viability and inflammatory factors,respectively.Results The cell activities of control group,model group,experimental-H group and experimental-H+SIRT1 agonist group were(100.00±3.56)％,(47.30±2.58)％,(57.33±3.41)％,(66.15±4.85)％,(76.78±2.83)％and(85.84±4.84)％;SIRT1 mRNA expression levels were 1.00±0.12,0.25±0.02,0.39±0.04,0.52±0.03,0.67±0.08 and 0.83±0.09;tumor necrosis factor-α(TNF-α)expression level were(15.03±1.21),(126.50±8.84),(112.60±12.29),(83.71±6.85),(53.88±3.43)and(28.19±4.02)pg·mL-1;the relative expression levels of PTEN-induced putative kinase 1(PINK1)protein were 0.30±0.03,0.26±0.04,0.39±0.04,0.65±0.06,0.89±0.12 and 1.28±0.08;the relative expression levels of gasdermin D-N(GSDMD-N)were 0.38±0.02,1.20±0.08,0.89±0.06,0.69±0.07,0.53±0.05 and 0.40±0.03,respectively.Compared with the model group,the above indexes in the experimental-H group were statistically different(all P＜0.05).There were statistically significant differences in the above indexes between the experimental-H+SIRT1 agonist group and the experimental-H group(all P＜0.05).Conclusion Rutin can induce mitochondrial autophagy by activating SIRT1,inhibit pyroptosis of nucleus pulposus cells and alleviate intervertebral disc degeneration in rats.

Objective To observe the effects of carvedilol on renal function in mice with diabetic kidney disease(DKD)and to preliminarily study its mechanism of action.Methods C57BL/6J male mice were randomly divided into control group,model group and experimental group,with 10 mice in each group.The mouse model of type Ⅰ diabetes was established by intraperitoneal injection of 150 mg·kg-1 streptozotocin(STZ).After successful modeling,the experimental group mice were given 10 mg·kg-1·d-1 carvedilol by gavage,while the control group and model group were given equal amounts of 0.9％NaCl.During the experiment,the fasting blood glucose(FBG)of mice were monitored weekly.After 8 weeks of administration,the urinary albumin to creatinine ratio(UACR),uric acid(UA),and other contents in the urine of mice were detected,as well as the levels of iron(Fe),superoxide dismutase(SOD),and malondialdehyde(MDA)in the renal tissue.And hematoxylin-eosin(HE)and Masson staining were performed on the renal tissue to observe the pathological changes of the kidney.Results After 8 weeks of administration,the UACR of the control group,model group and experimental group were(12.43±1.13),(63.01±20.78)and(19.79±1.94)mg·mmol-1;the UA levels were(132.10±10.14),(174.40±7.06)and(135.00±3.95)μmol·L-1;the Fe levels were(7.49±0.81),(9.98±0.46)and(7.02±0.60)μmol·g prot-1;the SOD activities were(34.56±0.58),(30.27±1.22)and(34.43±1.36)U·mg prot1;the MDA contents were(5.49±0.31),(7.72±0.17)and(4.46±0.32)nmol·mg prot-1.The differences between model group and normal group were statistically significant(all P＜0.05);compared between experimental group and model group,the difference were significant(all P＜0.05).Conclusion Carvedilol can alleviate the damage of renal function in diabetes mice,and its mechanism may be related to inhibiting iron death and alleviating oxidative stress injury.

Objective To investigate the bioequivalence of gliclazide sustained-release tablets in Chinese healthy subjects.Methods The study was designed using a single-center,open,randomized,single-dose,two-cycle,two-sequence administration method;subjects were orally administered the test/reference preparation 30 mg on an fasting or fed conditions,with self-cross-dosing.The concentration of gliclazide in human plasma was determined by liquid chromatography tandem mass spectrometry(LC-MS/MS)method.The main pharmacokinetic parameters of gliclazide(Cmax,AUC0-t and AUC0-∞)were analyzed by non-atrioventricular model of WinNonlin.Result In the fasting study,24 subjects were recruited and 22 completed the study.The main pharmacokinetic parameters of gliclazide sustained-release tablets test preparation and reference preparation in the fasting group were as follows:Cmax were(862.48±294.48)and(902.96±259.09)ng·mL-1;AUC0-t were(2.60 × 104±8 930.46)and(2.50 ×104±7 573.42)h·ng-1·mL-1;AUC0-∞ were(3.00 × 104±1.43 × 104)and(2.68 × 104±7 085.99)h·ng·mL-1.In the fed study,twenty-four subjects were enrolled and 23 completed the study.The main pharmacokinetic parameters of gliclazide sustained-release tablets test preparation and reference preparation in fed group:Cmax were(1 531.74±273.49)and(1 510.87±241.08)ng·mL-1;AUC0-t were(2.78 ×104±9 565.89)and(2.76 ×104±9 821.43)h·ng·mL-1;AUC0-∞ were(3.02 ×104±1.24 ×104)and(3.02 × 104±1.30 × 104)h·ng·mL-1 h·ng·mL-1.The 90％confidence intervals of the geometric mean ratios of Cmax,AUC0-t,AUC0-∞ for the test preparation and reference preparation gliclazide sustained-release tablets were all between 80％and 125％.Conclusion The test and the reference preparation of gliclazide sustained-release tablets are bioequivalent in Chinese healthy subjects.

Objective To investigate the application value of single nucleotide polymorphism(SNP)linkage analysis based on next-generation sequencing(NGS)technology in preimplantation genetic testing(PGT)of families with autosomal recessive polycystic kidney disease(ARPKD).Methods A family with ARPKD was selected,where the female member had a pregnancy ultrasound revealing polycystic kidney in the fetus.Genetic testing showed compound heterozygous mutations of the polycystic kidney/polycystic liver disease 1 gene(PKHD1),c.10444C>T(paternal)and c.4303del(maternal),with the c.4303del mutation being reported for the first time.Targeting the coding region of the PKHD1 gene,335 high-density tightly linked SNP sites were selected in the upstream and downstream 2M regions using multiplex polymerase chain reaction(PCR)and NGS.The couple′s SNP risk haplotypes carrying gene mutations were constructed.After in vitro fertilization,blastocyst culture was performed.Trophoblastic cells obtained from the biopsy were subjected to whole-genome amplification,and NGS was used for linkage analysis and low-depth chromosomal aneuploidy screening of the embryos.Sanger sequencing was used to verify the results of embryo linkage analysis.Results Among the 6 biopsied embryos,4 were mutation-free and euploid,1 exhibited heterozygous for the mutation and mosaic while another unstable sequencing data,making it impossible to judge.One of the mutation-free and developmentally healthy euploid embryos was implanted into the maternal uterus,resulting in the full-term delivery of a healthy baby.Conclusion Application of NGS-based SNP linkage analysis in PGT can effectively blocking the vertical transmission of ARPKD within families,while avoiding abortion issues caused by aneuploid embryos.This study is also the first PGT report target-ing the PKHD1 gene c.4303del mutation.

Objective To analyze the magnetic resonance images (MRI) of patients with spinal epidural lipomatosis (SEL) in high-altitude areas and to determine the optimal cut-off value for diagnosis with epidural fat thickness. Methods This retrospective study included patients who underwent lumbosacral MRI examination for lumbosacral pain in Ping’an District Hospital of Traditional Chinese Medicine, Haidong City, China from January 1, 2021 to December 31, 2022. The epidural fat thickness in vertebral segments T12/L1 to L5/S1 was compared between the SEL group and the non-SEL group. The diagnostic efficacy with different cut-off values at each vertebral segment was evaluated. Between-group comparisons were performed using the t-test, Mann-Whitney U test, chi-square test, or modified chi-square test. The area under the receiver operating characteristic (AUC) was used to evaluate the diagnostic efficiency. The DeLong test was used to compare AUC between the two groups. Results A total of 370 patients were included (60 in the SEL group and 310 in the non-SEL group). There were no significant differences in age, sex, height, body weight, and body mass index between the two groups (all P > 0.05). At different vertebral segments, the epidural fat thickness was significantly higher in the SEL group than in the non-SEL group (all P < 0.05). The cut-off values for SEL diagnosis with epidural fat thickness in segments T12/L1 to L5/S1 were 2.23, 4.25, 4.85, 5.57, 7.21, and 8 mm, respectively. The AUC of MRI SEL diagnosis with epidural fat thickness in segment L5/S1 was the highest (0.945, 95% confidence interval [CI]: 0.916-0.966, P < 0.001). SEL diagnosis with epidural fat thickness > 8 mm in segment L5/S1 was the most accurate, with an AUC of 0.931 (95% CI: 0.901-0.955, P < 0.001), a sensitivity of 95.0%, and a specificity of 91.3%; this AUC was significantly higher than those of diagnosis with other cut-off values (all P < 0.05). Conclusion SEL patients have significantly increased epidural fat in the spinal canal. Epidural fat thickness > 8 mm in segment L5/S1 can be used for diagnosis of SEL with improved efficiency and accuracy.

Objective To understand the characteristics and epidemic trend of syphilis in Wuhan from 2010 to 2021, and to provide a reference for the formulation of further prevention and control measures. Methods Data on Wuhan syphilis epidemics from 2010 to 2021 was collected from the China Disease Prevention and Control Information System. The epidemic characteristics and trends of syphilis were analyzed. Results From 2010 to 2021, a total of 36 628 confirmed cases of syphilis were reported in Wuhan, and the reported incidence rate decreased from 29.70/100 000 to 29.62/100 000, with an average annual decrease of 0.33% (P=0.843). Among them, the reported incidence of stage 1 syphilis decreased by 14.37% annually (P<0.001), stage 2 syphilis decreased by 18.59% annually (P<0.001), stage 3 syphilis decreased by 2.02% annually (P=0.523), and fetal syphilis decreased by 22.90% annually (P<0.001), while recessive syphilis increased by 9.19% annually (P<0.001). The ratio of male to female increased from 1.04:1 to 1.36:1 (P<0.001). The proportion of people aged 60 and above increased from 18.44% to 31.17% (P<0.001), and the 35-59 age group had the highest number of reported cases of syphilis in both men and women. Recessive syphilis was most common in men and women aged over 18 years old, and the proportion of recessive syphilis increased with age. Conclusion The prevention and control of syphilis has achieved phased results, especially in mother-to-child interruption and non-recessive syphilis control. On the basis of continuing to consolidate and strengthen the achievements of the current stage, the future syphilis prevention and control work should focus on and respond to the increasing trend of recessive syphilis cases, and take more targeted interventions for people over 60 years old, so as to further curb the spread of syphilis.

【Objective】 To objectively evaluate the quality control level of blood testing process in blood banks through quantitative monitoring and trend analysis, and to promote the homogenization level and standardized management of blood testing laboratories in blood banks. 【Methods】 A quality monitoring indicator system covering the whole process of blood collection and supply, including blood donation service, blood component preparation, blood testing, blood supply and quality control was established. The questionnaire Quality Monitoring Indicators for Blood Collection and Supply Process with clear definition of indicators and calculation formulas was distributed to 17 blood banks in Shandong province. Quality monitoring indicators of each blood bank from January to December 2022 were collected, and 31 indicators in terms of blood testing were analyzed using SPSS25.0 software. 【Results】 The proportion of unqualified serological tests in 17 blood bank laboratories was 55.84% for ALT, 13.63% for HBsAg, 5.08% for anti HCV, 5.62% for anti HIV, 18.18% for anti TP, and 1.65% for other factors (mainly sample quality). The detection unqualified rate and median were (1.23±0.57)% and 1.11%, respectively. The ALT unqualified rate and median were (0.74±0.53)% and 0.60%, respectively. The detection unqualified rate was positively correlated with ALT unqualified rate (r=0.974, P<0.05). The unqualified rate of HBsAg, anti HCV, anti HIV and anti TP was (0.15±0.09)%, (0.05±0.04)%, (0.06±0.03)% and (0.20±0.05)% respectively. The average unqualified rate, average hemolysis rate, average insufficient volume rate and the abnormal hematocrit rate of samples in 17 blood bank laboratories was 0.21‰, 0.08‰, 0.01‰ and 0.02‰ respectively. There were differences in the retest concordance rates of four HBsAg, anti HCV and anti HIV reagents, and three anti TP reagents among 17 blood bank laboratories (P<0.05). The usage rate of ELISA reagents was (114.56±3.30)%, the outage rate of ELISA was (10.23±7.05) ‰, and the out of range rate of ELISA was (0.90±1.17) ‰. There was no correlation between the out of range rate, outrage rate and usage rate (all P>0.05), while the outrage rate was positively correlated with the usage rate (r=0.592, P<0.05). A total of 443 HBV DNA positive samples were detected in all blood banks, with an unqualified rate of 3.78/10 000; 15 HCV RNA positive samples were detected, with an unqualified rate of 0.13/10 000; 5 HIV RNA positive samples were detected, with an unqualified rate of 0.04/10 000. The unqualified rate of NAT was (0.72±0.04)‰, the single NAT reaction rate [(0.39±0.02)‰] was positively correlated with the single HBV DNA reaction rate [ (0.36±0.02) ‰] (r=0.886, P<0.05). There was a difference in the discriminated reactive rate by individual NAT among three blood bank laboratories (C, F, H) (P<0.05). The median resolution rate of 17 blood station laboratories by minipool test was 36.36%, the median rate of invalid batch of NAT was 0.67%, and the median rate of invalid result of NAT was 0.07‰. The consistency rate of ELISA dual reagent detection results was (99.63±0.24)%, and the median length of equipment failure was 14 days. The error rate of blood type testing in blood collection department was 0.14‰. 【Conclusion】 The quality monitoring indicator system for blood testing process in Shandong can monitor potential risks before, during and after the experiment, and has good applicability, feasibility, and effectiveness, and can facilitate the continuous improvement of laboratory quality control level. The application of blood testing quality monitoring indicators will promote the homogenization and standardization of blood quality management in Shandong, and lay the foundation for future comprehensive evaluations of blood banks.

【Objective】 To establish an effective quality indicator monitoring system, scientifically and objectively evaluate the quality management level of blood banks, and achieve continuous improvement of quality management in blood bank. 【Methods】 A quality monitoring indicator system that covers the whole process of blood collection and supply was established, the questionnaire of Quality Monitoring Indicators for Blood Collection and Supply Process with clear definition of indicators and calculation formulas was distributed to 17 blood banks in Shandong. Statistical analysis of 21 quality monitoring indicators in terms of blood donation service (10 indicators), blood component preparation (7 indicators ), and blood supply (4 indicators) from each blood bank from January to December 2022 were conducted using SPSS25.0 software The differences in quality monitoring indicators of blood banks of different scales were analyzed. 【Results】 The average values of quality monitoring indicators for blood donation service process of 17 blood banks were as follows: 44.66% (2 233/5 000) of regular donors proportion, 0.22% (11/50) of adverse reactions incidence, 0.46% (23/5 000) of non-standard whole blood collection rate, 0.052% (13/25 000) of missed HBsAg screening rate, 99.42% (4 971/5 000) of first, puncture successful rate, 86.49% (173/200) of double platelet collection rate, 66.50% (133/200) of 400 mL whole blood collection rate, 99.25% (397/400) of donor satisfaction rate, 82.68% (2 067/2 500) of use rate of whole blood collection bags with bypass system with sample tube, and 1 case of occupational exposure in blood collection.There was a strong positive correlation between the proportion of regular blood donors and the collection rate of 400 mL whole blood (P<0.05). The platelet collection rate, incidence of adverse reactions to blood donation, and non-standard whole blood collection rate in large blood banks were significantly lower than those in medium and small blood banks (P<0.05). The average quality monitoring indicators for blood component preparation process of 17 blood banks were as follows: the leakage rate of blood component preparation bags was 0.03% (3/10 000), the discarding rate of lipemic blood was 3.05% (61/2 000), the discarding rate of hemolysis blood was 0.13%(13/10 000). 0.06 case had labeling errors, 8 bags had blood catheter leaks, 2.76 bags had blood puncture/connection leaks, and 0.59 cases had non-conforming consumables. The discarding rate of hemolysis blood of large blood banks was significantly lower than that of medium and small blood banks (P<0.05), and the discarding rate of lipemic blood of large and medium blood banks was significantly lower than that of small blood banks (P<0.05). The average values of quality monitoring indicators for blood supply process of 17 blood banks were as follows: the discarding rate of expired blood was 0.023% (23/100 000), the leakage rate during storage and distribution was of 0.009%(9/100 000), the discarding rate of returned blood was 0.106% (53/50 000), the service satisfaction of hospitals was 99.16% (2 479/2 500). The leakage rate of blood components during storage and distribution was statistically different with that of blood component preparation bags between different blood banks (P<0.05). There were statistically significant differences in the proportion of regular blood donors, incidence of adverse reactions, non-standard whole blood collection rate, 400 mL whole blood collection rate, double platelet collection rate, the blood bag leakage rate during preparation process, the blood components leakage rate during storage and distribution as well as the discarding rate of lipemic blood, hemolysis blood, expired blood and returned blood among large, medium and small blood banks (all P<0.05). 【Conclusion】 The establishment of a quality monitoring indicator system for blood donation services, blood component preparation and blood supply processes in Shandong has good applicability, feasibility and effectiveness. It can objectively evaluate the quality management level, facilitate the continuous improvement of the quality management system, promote the homogenization of blood management in the province and lay the foundation for future comprehensive evaluation of blood banks.