Kidney-tonifying and Blood-activating Prescription Regulates Wnt/β-catenin Signaling Pathway to Improve Uterine Spiral Artery Remodeling in Mouse Model of Recurrent Miscarriage / 中国实验方剂学杂志

ObjectiveTo observe the effects of the kidney-tonifying and blood-activating prescription on the Wnt/β-catenin signaling pathway and uterine spiral artery remodeling in a mouse model of recurrent miscarriage and to explore its underlying mechanism. MethodA mouse model of normal pregnancy was established by mating CBA/J mice with BALB/c mice. A mouse model of recurrent miscarriage was established by mating CBA/J mice with DBA/2 mice. The modeled mice of recurrent miscarriage were randomized into model， dydrogesterone， and low- and high-dose Chinese medicine groups. The mice in normal pregnancy were used as the control group. Each group consisted of 10 mice， and the drug administration lasted for 14 days. After the treatment， the embryo absorption rate of each group was recorded. Hematoxylin-eosin （HE） staining was employed to observe the pathological morphology of the uterine decidua， and the physiological transformation rate of spiral arteries （SPA） was evaluated. Real-time polymerase chain reaction （Real-time PCR） and Western blot were performed to determine the mRNA and protein levels， respectively， of matrix metalloproteinases （MMP）-2， MMP-9， vascular endothelial growth factor （VEGF）， and Wnt/β-catenin signaling pathway. ResultCompared with the control group， the model group presented increased embryo absorption rate （P<0.05）， decreased physiological transformation rate of uterine SPA （P<0.05）， cellular swelling， degeneration， and disordered arrangement in the uterine decidua tissue， and down-regulated mRNA and protein levels of key factors involved in SPA remodeling （MMP-2， MMP-9， VEGF） and the Wnt/β-catenin signaling pathway （Wnt2， β-catenin， Cyclin D1， c-Myc） （P<0.05）. Compared with the model group， both the low- and high-dose Chinese medicine reduced embryo absorption rate （P<0.05）， increased SPA physiological transformation rate （P<0.05）， improved uterine decidua tissue morphology， and increased decidua vessel count. Furthermore， they up-regulated the mRNA and protein levels of MMP-2， MMP-9， VEGF， and proteins in the Wnt/β-catenin signaling pathway （P<0.05）. ConclusionRecurrent miscarriage is associated with impaired uterine spiral artery remodeling. The kidney-tonifying and blood-activating prescription can promote uterine spiral artery remodeling by activating the Wnt/β-catenin signaling pathway and promoting the expression of VEGF， MMP-2， and MMP-9， thus treating recurrent miscarriage.

Immunogenicity, safety and immune persistence of the sequential booster with the recombinant protein-based COVID-19 vaccine (CHO cell) in healthy people aged 18-84 years / 中华预防医学杂志

Objective: To evaluate the immunogenicity, safety, and immune persistence of the sequential booster with the recombinant protein-based COVID-19 vaccine (CHO cell) in healthy people aged 18-84 years. Methods: An open-label, multi-center trial was conducted in October 2021. The eligible healthy individuals, aged 18-84 years who had completed primary immunization with the inactivated COVID-19 vaccine 3 to 9 months before, were recruited from Shangyu district of Shaoxing and Kaihua county of Quzhou, Zhejiang province. All participants were divided into three groups based on the differences in prime-boost intervals: Group A (3-4 months), Group B (5-6 months) and Group C (7-9 months), with 320 persons per group. All participants received the recombinant COVID-19 vaccine (CHO cell). Blood samples were collected before the vaccination and after receiving the booster at 14 days, 30 days, and 180 days for analysis of GMTs, antibody positivity rates, and seroconversion rates. All adverse events were collected within one month and serious adverse events were collected within six months. The incidences of adverse reactions were analyzed after the booster. Results: The age of 960 participants was (52.3±11.5) years old, and 47.4% were males (455). The GMTs of Groups B and C were 65.26 (54.51-78.12) and 60.97 (50.61-73.45) at 14 days after the booster, both higher than Group A's 44.79 (36.94-54.30) (P value<0.05). The GMTs of Groups B and C were 23.95 (20.18-28.42) and 27.98 (23.45-33.39) at 30 days after the booster, both higher than Group A's 15.71 (13.24-18.63) (P value <0.05). At 14 days after the booster, the antibody positivity rates in Groups A, B, and C were 91.69% (276/301), 94.38% (302/320), and 93.95% (295/314), respectively. The seroconversion rates in the three groups were 90.37% (272/301), 93.75% (300/320), and 93.31% (293/314), respectively. There was no significant difference among these rates in the three groups (all P values >0.05). At 30 days after the booster, antibody positivity rates in Groups A, B, and C were 79.60% (238/299), 87.74% (279/318), and 90.48% (285/315), respectively. The seroconversion rates in the three groups were 76.92% (230/299), 85.85% (273/318), and 88.25% (278/315), respectively. There was a significant difference among these rates in the three groups (all P values <0.001). During the sequential booster immunization, the incidence of adverse events in 960 participants was 15.31% (147/960), with rates of about 14.38% (46/320), 17.50% (56/320), and 14.06% (45/320) in Groups A, B, and C, respectively. The incidence of adverse reactions was 8.02% (77/960), with rates of about 7.50% (24/320), 6.88% (22/320), and 9.69% (31/320) in Groups A, B, and C, respectively. No serious adverse events related to the booster were reported. Conclusion: Healthy individuals aged 18-84 years, who had completed primary immunization with the inactivated COVID-19 vaccine 3 to 9 months before, have good immunogenicity and safety profiles following the sequential booster with the recombinant COVID-19 vaccine (CHO cell).

Noninvasive Diagnostic Technique for Nonalcoholic Fatty Liver Disease Based on Features of Tongue Images / 中国结合医学杂志

OBJECTIVE@#To investigate a new noninvasive diagnostic model for nonalcoholic fatty liver disease (NAFLD) based on features of tongue images.@*METHODS@#Healthy controls and volunteers confirmed to have NAFLD by liver ultrasound were recruited from China-Japan Friendship Hospital between September 2018 and May 2019, then the anthropometric indexes and sampled tongue images were measured. The tongue images were labeled by features, based on a brief protocol, without knowing any other clinical data, after a series of corrections and data cleaning. The algorithm was trained on images using labels and several anthropometric indexes for inputs, utilizing machine learning technology. Finally, a logistic regression algorithm and a decision tree model were constructed as 2 diagnostic models for NAFLD.@*RESULTS@#A total of 720 subjects were enrolled in this study, including 432 patients with NAFLD and 288 healthy volunteers. Of them, 482 were randomly allocated into the training set and 238 into the validation set. The diagnostic model based on logistic regression exhibited excellent performance: in validation set, it achieved an accuracy of 86.98%, sensitivity of 91.43%, and specificity of 80.61%; with an area under the curve (AUC) of 0.93 [95% confidence interval (CI) 0.68-0.98]. The decision tree model achieved an accuracy of 81.09%, sensitivity of 91.43%, and specificity of 66.33%; with an AUC of 0.89 (95% CI 0.66-0.92) in validation set.@*CONCLUSIONS@#The features of tongue images were associated with NAFLD. Both the 2 diagnostic models, which would be convenient, noninvasive, lightweight, rapid, and inexpensive technical references for early screening, can accurately distinguish NAFLD and are worth further study.

Investigation and analysis of adult skeletal fluorosis caused by drinking tea-type endemic fluorosis in Yushu Tibetan Autonomous Prefecture, Qinghai Province in 2021 / 中华地方病学杂志

Objective:To investigate the prevalence of adult skeletal fluorosis caused by drinking tea-type endemic fluorosis in Yushu Tibetan Autonomous Prefecture (hereinafter referred to as Yushu Prefecture), Qinghai Province, and provide scientific basis for prevention and control of the disease.Methods:In August 2021, one village was selected as a survey site in six counties (cities) in Yushu Prefecture, including Nangqian, Chindu, Yushu, Zadoi, Qumarlêb, and Zhiduo. Drinking water samples and 10 brick tea samples were collected from each village to determine the fluoride content in water and brick tea; at least 100 permanent residents aged ≥ 25, who had a habit of drinking brick tea and had lived in the local area for more than 5 years, were selected for X-ray imaging to examine the prevalence of adult skeletal fluorosis.Results:A total of 75 samples of residential drinking water were collected, with a fluoride content of (0.21 ± 0.05) mg/L, ranging from 0.11 to 0.34 mg/L; 60 samples of brick tea, with a fluoride content of (626.70 ± 157.27) mg/kg, ranging from 324.00 to 2 102.00 mg/kg. A total of 1 136 adults were examined, and 318 cases of skeletal fluorosis were diagnosed, with a detection rate of 27.99%. Among them, the detection rates of mild, moderate, and severe skeletal fluorosis were 20.95% (238/1 136), 6.07% (69/1 136), and 0.97% (11/1 136), respectively, with mild symptoms being the main. The detection rates of skeletal fluorosis in males and females were 29.09% (121/416) and 27.36% (197/720), respectively, with no statistically significant difference between the gender (χ 2 = 0.39, P = 0.533). Comparison of the skeletal fluorosis in different gender, the differences were statistically significant (χ 2 = 22.31, P < 0.001). The detection rates of skeletal fluorosis in the age groups of 25 - 35, 36 - 45, 46 - 55, 56 - 65, 66 - 75, and ≥76 years old were 6.86% (7/102), 22.37% (51/228), 24.02% (92/383), 37.44% (73/195), 43.48% (70/161), and 37.31% (25/67), respectively. The differences between the groups were statistically significant (χ 2 = 59.84, P < 0.001). Moreover, there was a statistically significant difference in the composition of skeletal fluorosis among different age groups ( H = 37.66, P < 0.001). The Spearman correlation analysis results showed that the severity of adult skeletal fluorosis was positively correlated with age ( r = 0.34, P < 0.001). Conclusions:There is a certain degree of prevalence of adult skeletal fluorosis in Yushu Prefecture. And as age increases, the condition of skeletal fluorosis becomes more severe.

Catheter-associated infection and influencing factors in anti-tumor chemo-therapy treated patients after indwelling peripherally inserted central ca-theter:analysis based on random forest model / 中国感染控制杂志

Objective To analyze the influencing factors for catheter-associated infection(CAI)in chemotherapy treated patients after indwelling peripherally inserted central catheter(PICC)based on a random forest model.Methods 400 tumor patients who received chemotherapy and PICC were selected and divided into the training set(n=300)and the test set(n=100)in a 3∶1 ratio through computer-generated random number.Patients in the training set were subdivided into the non-infection group and the infection group based on the occurrence of infec-tion.Clinical data from two groups of patients were compared.Influencing factors for the occurrence of CAI after PICC were analyzed with multivariate logistic regression model and the integrated classification algorithm of random forest model,and the predictive performance of the two methods was compared.Results Among 300 chemotherapy treated patients in the training set,32 cases(10.67％)experienced CAI.Compared with the non-infection group,patients in the infection group had more single punctures for catheterization,longer PICC retention time,larger pro-portion of catheter movement,larger proportion of complication with diabetes,higher frequency of dressing chan-ges,lower white blood cell count and immune function(all P＜0.05).PICC retention time,catheter movement,complication with diabetes,dressing change frequency,white blood cell(WBC)and immune function were inde-pendent influencing factors for CAI after PICC(all P＜0.05).The random forest model showed that ranking by the importance of different influencing factors was as following:PICC retention time,catheter movement,complication with diabetes,WBC,dressing change frequency and immune function.The integrated classification algorithm of random forest model for predicting the occurrence of CAI in chemotherapy treated patients showed that the area un-der the receiver operating characteristic(ROC)curve(AUC)was 0.872,which had better prediction performance compared with the logistic regression model(AUC=0.791).Conclusion PICC retention time,catheter movement,complicated with diabetes,dressing change frequency,WBC level and immune function are independent influencing factors for CAI in chemotherapy treated patients.The integrated classification algorithm of random forest model can be used to predict CAI in chemotherapy treated patients,and its prediction performance is better than that of the logistic regression model.

Application value of CT texture analysis for evaluating Ki-67 expression in patient with esophageal squamous cell carcinoma / 实用放射学杂志

Objective To explore the application value of CT texture analysis for evaluating Ki-67 expression in patient with esophageal squamous cell carcinoma.Methods Sixty-one cases of pathologically confirmed esophageal squamous cell carcinoma patients were selected to obtain the Ki-67 protein expression status of the patients'pathological tissues,and the patients were divided into a high-expression group and a low-expression group.All patients underwent plain and enhanced chest CT within two weeks before surgery.Lesions delineation and texture feature extraction of esophageal cancer were obtained via Omni-Kinetics software.The texture parameters included Min Intensity,Max Intensity,Median Intensity,Mean Intensity,Deviation,Skewness,Kurtosis,Entropy,Energy,Correlation,Haralick,short run high grey level emphasis(SRHGLE),short run low grey level emphasis(SRLGLE),long run high grey level emphasis(LRHGLE),long run low grey level emphasis(LRLGLE),Grey Level Nonuniformity,Run Length Nonuniformity.The differences of texture features among different Ki-67 expression groups were compared,and the receiver operating characteristic(ROC)curve was used to analyze the predictive value of Ki-67 expression in patient with esophageal cancer.Results In plain CT images,the SRHGLE and Grey Level Nonuniformity of the high expression group were significantly higher than those of the low expression group(P=0.010,0.002,respectively).In enhanced CT images,the Mean Intensity,Entropy and Grey Level Nonuniformity of the high expression group were significantly higher than those of the low expression group(P=0.026,0.037,0.001,respectively),and SRHGLE and LRHGLE of the high expression group were significantly lower than those of the low expression group(P=0.016,0.010,respectively).The area under the curve(AUC)of texture features in plain CT were 0.676-0.740,and the AUC of combined diagnosis reached 0.770[95%confidence interval(CI):0.645,0.868],and sensitivity and specificity was 0.921,0.565,respectively.In enhanced CT,the AUC of texture features were 0.629-0.750,the AUC of combined diagnosis increased to 0.903(95%CI:0.799,0.964),and sensitivity and specificity was 0.816,0.826,respectively.Conclusion CT texture analysis can early and non-invasively predict Ki-67 expression in patient with esophageal squamous cell carcinoma,it can be used as an imaging marker to evaluate the proliferative activity of esophageal cancer cells,and may provide diagnosis and treatment information for clinical decision-making of esophageal squamous cell carcinoma.

Application of quality monitoring indicators of blood testing in blood banks of Shandong province / 中国输血杂志

【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, P0.05), 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.

Quality monitoring indicator system in blood banks of Shandong: applied in blood donation services, component preparation and blood supply process / 中国输血杂志

【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.

Changes of circulating Ectodysplasin A levels and its analysis of influencing factors in polycystic ovary syndrome / 中国糖尿病杂志

Objective To investigate the serum Ectodysplasin A(EDA)levels in women with polycystic ovary syndrome(PCOS)and explore the correlation of EDA and insulin resistance(IR).Methods A total of 256 newly diagnosed PCOS patients in Guangzhou First People's Hospital from September 2020 to September 2022 were selected.Taking BMI=25 kg/m2 as the cut-off point,the patients with PCOS were divided into obese subgroup(n=143)and non-obese subgroup(n=113).Among them,43 PCOS received six months of Liraglutide intervention.123 healthy women were normal control group(NC),which were divided into healthy obese subgroup(n=10)and healthy non-obese subgroup(n=113).Serum EDA and related biochemical indexes were detected in both groups.The correlation between serum EDA and metabolic index were analyzed.Results The serum EDA level in PCOS group was higher than that in NC group[(272.59±68.52)vs(214.51±61.36)pg/ml,P<0.05].Serum EDA in obese subgroup was higher than that in no-obese subgroup in PCOS patients[(301.11±55.81)vs(236.84±66.25)pg/ml,P<0.01].After the intervention of Liraglutide,serum EDA in PCOS women markedly decreased[(294.71±57.81)vs(336.0±61.23)pg/ml,P<0.05].EDA levels were correlated positively with body mass index(BMI),waist hip ratio(WHR),fasting blood glucose(FPG),2 hPG,fasting insulin,2 hIns,homeostasis model assessment for insulin resistance(HOMA-IR),TC,LDL-C and testosterone.Multiple stepwise regression analysis showed that BMI and HOMA-IR were independent risk factors of serum EDA.Conclusion Serum EDA is elevated in PCOS patients,especially when combined with obesity,which may be related to IR.Liraglutide intervention can significantly reduce EDA levels in PCOS patients.

Visualization Analysis on Research Literature of TCM Regulation of miRNA / 中国中医药信息杂志

Objective To analyze the current status and trends of TCM regulation of microRNA(miRNA)using visualization methods.Methods The literature related to the TCM regulation of miRNA was retrieved from CNKI,VIP and Wanfang Data from the establishment of the databases to May 31,2022.Excel 2019,VOSviewer 1.6.18,and CiteSpace 5.8.R3 software were applied to visualize and analyze the year of publication,journal source,author and keywords of the included literature.Results A total of 787 articles were included,and the number of publications continued to rise.Source journals with more publications includes Chinese Journal of Experimental Traditional Medical Formulas,China Journal of Traditional Chinese Medicine and Pharmacy,Chinese Archives of Traditional Chinese Medicine,etc.Research teams were formed with Wang Jie,Liu Xide,Diao Limei,etc.as the representatives,and the cooperation among the teams was not very close.Analysis on the keywords in the literature showed that the studies mainly focused on apoptosis,miRNA-21,electroacupuncture,atherosclerosis,proliferation and other related fields;TCM intervention that accounted for the most research were extracts of Chinese materia medica,with 42%of the studies;there were 24 miRNAs studied≥3 times,and the most studied miRNA was miRNA-21.Conclusion The research hotspots of TCM regulation of miRNA are mainly the molecular mechanism of various TCM therapeutic tools to improve cell autophagy,apoptosis,inflammatory response and other pathways through regulation of miRNAs.The trend of research is to study the mechanism of empirical prescriptions of famous TCM practitioners based on precise therapeutic strategies.

Discussion on Effects of Electroacupuncture on Intestinal Flora and Serum Inflammation Factors in Rheumatoid Arthritis Rabbits Based on"Gut-joint"Axis / 中国中医药信息杂志

Objective To observe the effects of electroacupuncture on intestinal flora and serum inflammatory factors in rabbit model with rheumatoid arthritis(RA);To explore the mechanism of its therapeutic effect on RA.Methods RA model rabbits were established by ovalbumin induction combined with Freund's complete adjuvant,and the rabbits after successful modeling were randomly divided into model group,probiotic group and electroacupuncture group,with 6 rabbits in each group.Another 6 rabbits were set as the normal group.The electroacupuncture group received electroacupuncture at the bilateral"Zusanli"and"Dubi"for 30 minutes,the probiotic group was given probiotic capsules solution(14.5 mg/kg)by gavage,once a day,for two consecutive weeks.The knee joint circumference and pain threshold of rabbits were measured,histopathological morphological changes of colonic tissue and synovial tissue ws observed by HE staining,16S rDNA sequencing was used to analyze structural changes of intestinal flora,the contents of TNF-α,IL-1β and IL-6 in serum were detected by ELISA.Results Compared with the normal group,the circumference of knee joint of rabbits in the model group increased significantly,the pain threshold was significantly decreased(P<0.01);the colonic mucosal damage was serious,the goblet cells were missing,a large number of inflammatory cells were infiltrate;the joint capsule synovial surface was rough,the synovial cell layer was hyperplasia and thickening,the synovial tissue inflammatory cell infiltration was obvious;the number and evenness of gut microbiota species decreased,while the relative abundance of Proteobacteria,Firmicutes,and Bacteroidetes decreased(P<0.05,P<0.01),the relative abundance of Desulfobacteria increased(P<0.01),while the relative abundance of Campylobacter,Lawsonella,and Pseudomonas increased(P<0.01),while the relative abundance of Heshanomonas and Herbaspirillum decreased(P<0.01);the contents of serum TNF-α,IL-1β and IL-6 increased(P<0.01).Compared with the model group,the knee joint circumference of the probiotic group and the electroacupuncture group decreased,the pain threshold increased(P<0.01,P<0.05);the degree of intestinal mucosal damage was reduced,the goblet cells were basically arranged neatly,the inflammatory cell infiltration was reduced;synovial cells proliferation and thickening decreased,with a small amount of inflammatory cell infiltration;the number and evenness of gut microbiota species increased,while the relative abundance of Proteobacteria,Firmicutes,and Bacteroidetes increased(P<0.05,P<0.01),the relative abundance of Desulfobacteria decreased(P<0.01),while the relative abundance of Campylobacter,Lawsonella and Pseudomonas decreased(P<0.01),the relative abundance of Heshanomonas and Herbaspirillum increased(P<0.05,P<0.01);the contents of serum TNF-α,IL-1β and IL-6 significantly decreased(P<0.01).Conclusion Electroacupuncture can significantly improve the symptoms of RA rabbits and reduce the inflammatory reaction in synovial tissue of joint,and the mechanism may be related to the regulation of intestinal flora structure.

Association between urinary metal levels and kidney stones in metal smelter workers / 环境与职业医学

Background Arsenic, cobalt, barium, and other individual metal exposure have been confirmed to be associated with the incidence of kidney stones. However, there are few studies on the association between mixed metal exposure and kidney stones, especially in occupational groups. Objective To investigate the association between mixed metal exposure and kidney stones in an occupational population from a metal smelting plant. Methods A questionnaire survey was conducted to collect sociodemographic characteristics, medical history, and lifestyle information of 1158 mixed metal-exposed workers in a metal smelting plant in Guangdong Province from July 2021 to January 2022. Midstream morning urine samples were collected from the workers, the concentrations of 18 metals including lithium, vanadium, chromium, manganese, cobalt, nickel, copper, zinc, arsenic, selenium, strontium, molybdenum, cadmium, cesium, barium, tungsten, titanium, and lead were measured by inductively coupled plasma mass spectrometry, and the urinary mercury levels were measured by cold atomic absorption spectroscopy. Based on predetermined inclusion criteria, a total of 919 mixed metal-exposed workers were included in the study, including 117 workers in the kidney stone group and 802 workers in the non-kidney stone group. With a detection rate of urinary metals greater than 80% as entry criterion, 16 eligible metals were finally included for further analysis. Parametric or non-parametric methods were used to compare the differences between continuous or categorical variables of the non-kidney stone group and the kidney stone group. Logistic regression models were constructed to explore the association between individual metal exposures and kidney stones. Weighted quantile sum (WQS) regression models were used to evaluate the association between mixed metal exposure and kidney stones, as well as the weights of each metal on kidney stones. Then Bayesian kernel machine regression (BKMR) models were used to explore the overall effect of mixed metal exposure on renal calculi and the potential interactions between metals. Results We found that there were significant differences in sex, age, length of service, and body mass Index (BMI) between the non-kidney stone group and the kidney stone group (P<0.05). The urinary concentrations of molybdenum and barium in the kidney stone group were higher than those in the non-kidney stone group, and the differences were statistically significant (P<0.05). The logistic regression models demonstrated that urinary cobalt, arsenic, molybdenum, and barium were positively correlated with the risk of kidney stones (Ptrend<0.05). The WQS regression models showed that the mixed exposure to vanadium, cobalt, arsenic, molybdenum, and barium was positively associated with the risk of kidney stones (P<0.05). Among them, molybdenum, arsenic, and barium accounted for 0.391, 0.337, and 0.154, respectively. The BKMR results revealed a positive association between metal mixture exposure and the risk of kidney stones (P<0.05). When other metals were fixed at the 25th, 50th, or 75th percentile, arsenic, molybdenum, cobalt, and barium exhibited significant positive effects on the risk of kidney stones (P<0.05), while vanadium showed a significant negative effect (P<0.05). The interaction analysis demonstrated interactions between barium and cobalt, as well as between vanadium and cobalt (P<0.05). Conclusion In the occupational population of this smelter, occupational mixed metal exposure could increase the risk of kidney stones, and the main metals are molybdenum, arsenic, barium, and cobalt.

Asia-Pacific consensus on long-term and sequential therapy for osteoporosis

Objectives@#This study aimed to present the Asia-Pacific consensus on long-term and sequential therapy for osteoporosis, offering evidence-based recommendations for the effective management of this chronic condition.The primary focus is on achieving optimal fracture prevention through a comprehensive, individualized approach. @*Methods@#A panel of experts convened to develop consensus statements by synthesizing the current literature and leveraging clinical expertise. The review encompassed long-term anti-osteoporosis medication goals, first-line treatments for individuals at very high fracture risk, and the strategic integration of anabolic and anti resorptive agents in sequential therapy approaches. @*Results@#The panelists reached a consensus on 12 statements. Key recommendations included advocating for anabolic agents as the first-line treatment for individuals at very high fracture risk and transitioning to anti resorptive agents following the completion of anabolic therapy. Anabolic therapy remains an option for in dividuals experiencing new fractures or persistent high fracture risk despite antiresorptive treatment. In cases of inadequate response, the consensus recommended considering a switch to more potent medications. The consensus also addressed the management of medication-related complications, proposing alternatives instead of discontinuation of treatment. @*Conclusions@#This consensus provides a comprehensive, cost-effective strategy for fracture prevention with an emphasis on shared decision-making and the incorporation of country-specific case management systems, such as fracture liaison services. It serves as a valuable guide for healthcare professionals in the Asia-Pacific region, contributing to the ongoing evolution of osteoporosis management.

Immunogenicity, safety and immune persistence of the sequential booster with the recombinant protein-based COVID-19 vaccine (CHO cell) in healthy people aged 18-84 years / 中华预防医学杂志

Objective: To evaluate the immunogenicity, safety, and immune persistence of the sequential booster with the recombinant protein-based COVID-19 vaccine (CHO cell) in healthy people aged 18-84 years. Methods: An open-label, multi-center trial was conducted in October 2021. The eligible healthy individuals, aged 18-84 years who had completed primary immunization with the inactivated COVID-19 vaccine 3 to 9 months before, were recruited from Shangyu district of Shaoxing and Kaihua county of Quzhou, Zhejiang province. All participants were divided into three groups based on the differences in prime-boost intervals: Group A (3-4 months), Group B (5-6 months) and Group C (7-9 months), with 320 persons per group. All participants received the recombinant COVID-19 vaccine (CHO cell). Blood samples were collected before the vaccination and after receiving the booster at 14 days, 30 days, and 180 days for analysis of GMTs, antibody positivity rates, and seroconversion rates. All adverse events were collected within one month and serious adverse events were collected within six months. The incidences of adverse reactions were analyzed after the booster. Results: The age of 960 participants was (52.3±11.5) years old, and 47.4% were males (455). The GMTs of Groups B and C were 65.26 (54.51-78.12) and 60.97 (50.61-73.45) at 14 days after the booster, both higher than Group A's 44.79 (36.94-54.30) (P value<0.05). The GMTs of Groups B and C were 23.95 (20.18-28.42) and 27.98 (23.45-33.39) at 30 days after the booster, both higher than Group A's 15.71 (13.24-18.63) (P value <0.05). At 14 days after the booster, the antibody positivity rates in Groups A, B, and C were 91.69% (276/301), 94.38% (302/320), and 93.95% (295/314), respectively. The seroconversion rates in the three groups were 90.37% (272/301), 93.75% (300/320), and 93.31% (293/314), respectively. There was no significant difference among these rates in the three groups (all P values >0.05). At 30 days after the booster, antibody positivity rates in Groups A, B, and C were 79.60% (238/299), 87.74% (279/318), and 90.48% (285/315), respectively. The seroconversion rates in the three groups were 76.92% (230/299), 85.85% (273/318), and 88.25% (278/315), respectively. There was a significant difference among these rates in the three groups (all P values <0.001). During the sequential booster immunization, the incidence of adverse events in 960 participants was 15.31% (147/960), with rates of about 14.38% (46/320), 17.50% (56/320), and 14.06% (45/320) in Groups A, B, and C, respectively. The incidence of adverse reactions was 8.02% (77/960), with rates of about 7.50% (24/320), 6.88% (22/320), and 9.69% (31/320) in Groups A, B, and C, respectively. No serious adverse events related to the booster were reported. Conclusion: Healthy individuals aged 18-84 years, who had completed primary immunization with the inactivated COVID-19 vaccine 3 to 9 months before, have good immunogenicity and safety profiles following the sequential booster with the recombinant COVID-19 vaccine (CHO cell).

The molecular mechanism of spleen-strengthening and moisture-nourishing liver prescription in treatment of acute-on-chronic liver failure based on network pharmacology and experimental verification / 中国药理学通报

To explore the mechanism of spleen- were obtained for the treatment of acute-on-chronic livstrengthening and moisture-nourishing liver prescription er failure, and 244 intersecting target genes and 7 core (JPLSYGF) in the treatment of acute-on-chronic liver target genes were screened. Molecular docking showed failure using network pharmacology and the molecular that the core target genes AKT1, SRC, VEGFA, docking. Methods Relying on TCMSP and Gene- STAT3 , EGFR, MAPK3 , HRAS had good affinity with Cards and other databases, the relevant targets of JPL- quercetin, the main active component in the JPLSYGF in the treatment of acute-on-chronic liver failure SYGF, and had strong binding activity. In addition, in were obtained. String and Cytoscape were used to con- vivo tests verified that the JPLSYGF could reduce the struct PPI networks of targets, core targets were expression of HRAS, EGFR, STAT3 , SRC, and VEGscreened out, and DAVID was used for GO function FA, to delay the progression of acute-on-chronic liver annotation and KEGG pathway enrichment analysis. failure. Conclusions JPLSYGF may act on core tar- The main active ingredients of the traditional Chinese gets such as HRAS, EGFR, STAT3, SRC, VEGFA medicine compound formula for JPLSYGF were select- and so on, to achieve the effect of treating acute-oned with a bioavailability OB value of =Э 30% and a chronic liver failure. drug-like DL

Research progress of natural product evodiamine-based antitumor drug design strategies / 药学学报

Natural products are important sources for the discovery of anti-tumor drugs. Evodiamine is the main alkaloid component of the traditional Chinese herb Wu-Chu-Yu, and it has weak antitumor activity. In recent years, a number of highly active antitumor candidates have been discovered with a significant progress. This article reviews the research progress of evodiamine-based antitumor drug design strategies, in order to provide reference for the development of new drugs with natural products as leads.

Association between exposure to lead, cadmium, and arsenic and blood pressure in workers from a smelter / 环境与职业医学

Background Occupational exposure to lead, cadmium, or arsenic is a potential risk factor for blood pressure elevation. Current studies mainly focus on the relationship between a single metal and blood pressure. However, mixed metal exposure often exists in the actual working environment, and the interactive effects of polymetallic interactions on blood pressure and the dose-effect relationship remain unclear yet. Objective To explore the influence proportion of occupational exposure to lead, cadmium, or arsenic on blood pressure and their interactive effects. Methods From January to December 2021, workers from a smelter in southern China were selected. Demographic characteristics, height, weight, and blood pressure of workers were collected through questionnaire and physical examination. At the same time, their urine samples were collected and the levels of urinary lead, urinary cadmium, and urinary arsenic were detected by inductively coupled plasma mass spectrometry, and corrected by urinary creatinine (Cr). Linear regression and logistic regression were used to analyze the relationship between urinary lead, cadmium, and arsenic and blood pressure. Weighted quantile sum (WQS) regression was applied to evaluate the dose-effect relationship between urinary lead, cadmium, and arsenic exposures and blood pressure and the effect weight of each metal on blood pressure. Generalized linear regression and additive/multiplicative scaling were used to identify interactive effects of the three metals on blood pressure. Results A total of 1075 workers were included in this study, with a mean age of (44.68±5.11) years and mean working seniority of (24.66±5.23) years. There were 891 males (88.9%) and 184 were females (17.1%); 24.7% workers were drinkers and 45.7% workers were smokers; 302 workers (28.1%) reported hypertension and 37 of them were taking antihypertensive drugs. The P50 (P25, P75) levels of urinary lead, urinary cadmium, and urinary arsenic were 6.11 (3.71, 11.08), 3.88 (2.68, 5.44), and 26.04 (19.99, 35.11) μg·g−1, respectively. After adjusting for gender, age, working seniority, body mass index, smoking, drinking, and the usage of antihypertensive drugs, systolic and diastolic blood pressure increased by 0.772 and 0.418 mmHg respectively for 10% increase in lead, cadmium, and arsenic mixed exposure. Urinary cadmium, among the three single exposures, had the greatest effect on systolic and diastolic blood pressure, weight (w)=0.523 and 0.551 respectively. The interaction of urinary lead and urinary cadmium was positively correlated with the occurrence of hypertension, multiplicative interaction OR (ORint)=1.88 (95%CI: 1.09, 3.63), attributable proportion due to interaction (AP)=1.19 (95%CI: 0.40, 8.18). Conclusion This study shows that mixed exposure to lead, cadmium, and arsenic has a positive relationship with blood pressure, in which cadmium plays a major role. Co-exposure to lead and cadmium has a positive interactive effect on hypertension development and systolic blood pressure elevation.

Association between combined exposure of heavy metals and biomarkers of early renal damage in occupational population / 中国职业医学

Objective: To investigate the effect of combined exposure to four heavy metals (lead, cadmium, arsenic, mercury) on early kidney injury in occupational population. Methods: A total of 384 workers exposed to combined heavy metals in a non-ferrous metal smelting plant in Guangdong Province were selected as the research subjects using judgment sampling method. The levels of blood lead, urinary cadmium and urinary arsenic were detacted by inductively coupled plasma mass spectrometry, while urinary mercury levels were measured using cold atomic absorption spectroscopy (acidic tin chloride reduction method). The levels of biomarkers such as urinary β2-microglobulin (β2-MG), kidney injury molecule-1 (Kim-1) and neutrophil gelatinase-associated lipocalin (NGAL) were detected by enzyme-linked immunosorbent assay. Spearman correlation analysis, linear regression, weighted quantile sum (WQS) regression and Bayesian kernel machine regression (BKMR) models were used to analyze the association between the exposure to the four heavy metals and early kidney injury biomarkers. Results: The median of blood lead, urinary cadmium, urinary arsenic and urinary mercury were 0.47 μmol/L and 4.450, 27.790 and 0.520 μg/gCr, respectively. The median of urinary β2-MG, Kim-1 and NGAL were 62.960, 1.130 and 18.150 μg/gCr, respectively. Spearman correlation analysis showed that urinary levels of β2-MG, Kim-1, and NGAL were weakly correlated with blood lead and urinary mercury levels (all P<0.01), but not correlated with urinary cadmium and urinary arsenic (all P>0.05). The results of multiple linear regression analysis showed that urinary mercury was positively correlated with urinary β2-MG, Kim-1 and NGAL (all P<0.01), urinary arsenic was positively correlated with urinary β2-MG level (P<0.01), and blood lead was negatively correlated with urinary β2-MG and Kim-1 (all P<0.05). The WQS regression analysis showed that the combined effect of the four heavy metals was positively correlated with urinary β2-MG, Kim-1 and NGAL (all P<0.01), with mercury having the highest impact and lead the lowest. BKMR model analysis showed the increasing trend in urinary β2-MG, Kim-1 and NGAL with the increasing levels of the combined exposure to the four heavy metals. Urinary β2-MG, Kim-1 and NGAL decreased when urinary mercury level increased from the 25th percentile to the 75th percentile and the other metals were correspondingly fixed at a certain level. When the blood exposure levels of other metals remained at the corresponding median levels, urinary β2-MG, Kim-1 and NGAL levels were positively correlated with urinary arsenic level, but no significant linear dose-response relationship was observed with the other three heavy metals. Conclusion: sLead, arsenic, and mercury are independently associated with early kidney injury biomarkers in occupational population from non-ferrous metal smelting. The four heavy metals had positive combined effects on urinary β2-MG, Kim-1 and NGAL, with mercury having the greatest impact.

Analysis of incidence and influencing factors of interstitial pneumonia in diffuse large B-cell lymphoma after treatment of R-CHOP-like regimens / 白血病·淋巴瘤

Objective:To investigate the incidence of interstitial pneumonia (IP) and its risk factors in newly-diagnosed diffuse large B-cell lymphoma (DLBCL) after treatment of R-CHOP regimen (rituximab combined with cyclophosphamide + doxorubicin + vincristine + prednisone) and R-CDOP regimen (rituximab combined with cyclophosphamide + vincristine + liposomal doxorubicin + prednisone).Methods:The clinical data of 54 newly-diagnosed DLBCL patients who were admitted to the Central Hospital Affiliated to Shandong First Medical University from January 2015 to August 2020 were retrospectively analyzed, of which 25 cases were treated with R-CDOP regimen, and 29 cases were treated with R-CHOP regimen. The incidence of IP was compared in patients stratified according to different clinically factors, and the risk factors of IP were analyzed by multivariate logistic regression.Results:The patients with R-CDOP regimen [compared with R-CHOP regimen: 32.0% (8/25) vs. 3.4% (1/29)], normal lactate dehydrogenase level before treatment [compared with high level: 29.0% (9/31) vs. 0 (0/23)], eosinophilic count>0.1×10 9/L [compared with ≤0.1×10 9/L: 28.0% (7/25) vs. 6.9% (2/29)] and Ki-67 positive index<80% [compared with ≥80%: 23.1% (9/39) vs. 0 (0/15)] had a higher incidence of IP (all P<0.05), there were no statistical differences in the incidence of IP among patients stratified with age, gender, smoking history, underlying disease, stage, international prognostic index score, Eastern Cooperative Oncology Group score, type, B symptoms, β 2-microglobulin, and lymphocyte count (all P>0.05). Multivariate logistic regression analysis showed that the application of R-CDOP regimen was the independent risk factor for the incidence of IP (compared with R-CHOP regimen: OR = 2.898, 95% CI 1.358-6.176, P = 0.008). Conclusions:The application of chemotherapy with R-CDOP regimen in DLBCL patients increases the incidence risk of IP, which needs to be closely monitored and prevented during treatment.

Analysis of external quality control assessment results of fluorine and arsenic in Qinghai Province in 2021 / 中华地方病学杂志

Objective:To learn about the detection quality and external quality control assessment of fluoride and arsenic in laboratories at all levels in Qinghai Province.Methods:The Z-score method was used to analyze and evaluate the evaluation results of 1 provincial, 8 municipal and 43 county level laboratories of disease prevention and control institutions participating in the external quality control assessment of water fluoride and brick tea fluoride in Qinghai Province in 2021, as well as 1 provincial, 1 municipal and 2 county level laboratories of disease prevention and control institutions participating in the external quality control assessment of water arsenic and urine arsenic. The feedback rate and qualification rate of external quality control of each assessment laboratory were calculated.Results:In 2021, the feedback rate of external quality control of water fluoride, brick tea fluoride, water arsenic and urine arsenic in provincial and municipal level laboratories of Qinghai Province were 100.00%; except that the qualified rate of water fluoride was 7/9, the qualified rate of external quality control of other projects was 100.00%. The feedback rate of external quality control of water fluoride, brick tea fluoride, water arsenic and urine arsenic in county level laboratories was 100.00%; except that the qualified rate of water fluoride was 86.05% (37/43), the qualified rate of external quality control of other projects was 100.00%. In the specific assessment results of the laboratory, the assessment results of water fluoride sample FS20210101 from 1 provincial, 1 municipal and 2 county level laboratories, and FS20210102 from 1 county level laboratory were suspicious; the assessment results of water fluoride sample FS20210101 from 3 county level laboratories were not satisfactory; the assessment results of fluoride and arsenic sample in other laboratories were satisfactory.Conclusions:The qualified rate of external quality control of fluoride and arsenic in laboratories at all levels in Qinghai Province is relatively high, but some county level laboratories are still dissatisfied with the assessment results of water fluoride. Therefore, it is necessary to strengthen the detection level of water fluoride in laboratories.