1.Mechanism of Buzhong Yiqitang in Ameliorating Thyroiditis Damage in AIT Mice by Modulating TLR4/NF-κB/AIM2 Signaling Pathway
Zhuo ZHAO ; Zhe JIN ; Zhengzheng LI ; Xuanlin GUO ; Jiayun LI ; Tongran GAO ; Pin LI ; Zhimin WANG ; Yuanping YIN ; Ziyu LIU ; Xiao YANG
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(18):1-9
ObjectiveTo explore the mechanism of Buzhong Yiqitang in ameliorating inflammatory injury in autoimmune thyroiditis (AIT) mice based on the Toll-like receptor 4(TLR4)/nuclear transcription factor-kappa B(NF-κB)/absent in melanoma 2(AIM2)inflammasome signaling pathway. MethodThe 120 genetically susceptible 8-week-old NOD.H-2h4 mice were selected and randomly divided into control group, model group, low, medium and high dose groups of Buzhong Yiqitang (4.78, 9.56, 19.12 g·kg-1), and western medicine group (selenium yeast tablets, 3.033×10-5 g·kg-1). The AIT model mice in each group drank ad libitum 0.05% sodium iodide aqueous solution for 8 weeks to establish the AIT model, and the control group drank ad libitum distilled water. Eight weeks later, the mice in each dosing group were divided into groups and gavage. The swelling of thyroid tissue was observed with the naked eye, and the weight of spleen was weighed. The content of serum inflammatory factors interleukin-1β (IL-1β), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) was measured by enzyme-linked immunosorbent assay (ELISA), and Real-time PCR was used to detect the expression of HMGB1, TLR4, AIM2, NF-κB p65,apoptosis-associated speck-like protein(ASC),cysteinyl aspartate-specific protease-1(Caspase-1), IL-1β mRNA. Western blot was used to detect the expression of high motility group protein 1 (HMGB1), TLR4, AIM2, NF-κB p65, phosphorylation(p)-NF-κB p65, ASC, Caspase-1, and IL-1β proteins in thyroid tissue, and immunofluorescence staining was used to observe the protein expression of HMGB1, AIM2, and NF-κB p65 in thyroid tissue of mice. ResultCompared with the control group, the thyroid tissue of mice in the model group was significantly swollen, the spleen quality was significantly increased, and the expression of HMGB1, TLR4, NF-κB p65, AIM2, ASC, Caspase-1, IL-1β in thyroid tissue was significantly increased (P<0.01). Compared with the model group, the swelling of thyroid tissue in mice in each dose group of Buzhong Yiqitang was improved, the quality of spleen was significantly reduced, and the expression of HMGB1, TLR4, AIM2, NF-κB p65, p-NF-κB p65, ASC, Caspase-1, IL-1β in thyroid tissue was significantly reduced (P<0.05, P<0.01). ConclusionBuzhong Yiqitang can effectively improve the inflammatory injury of AIT, and regulating the abnormal activation of the TLR4/NF-κB/AIM2 inflammasome signal pathway may be one of its intervention mechanisms.
2.A comparative study of NQAD and ELSD for the determination of peimine and peiminine in huangshi xiangsheng pills
Huiyi LIU ; Limin ZUO ; Xiaodan QIU ; Xin GUO ; Xiaofang LIAN ; Qingying JIA ; Yongsheng GU ; Xuanlin LIU ; Guangzhi SHAN
Drug Standards of China 2024;25(6):529-535
Objective:The study aimed to quantify the contents of peimine and peiminine in huangshi xiangsheng pills using a nano quantity analyte detector(NQAD)and compare the results with the evaporative light scattering detector(ELSD).Methods:Analytical separation was conducted utilizing a CAPCELL PAK MG Ⅲ C18 column(4.6 mm ×250 mm,5 μmi)as the stationary phase.The mobile phase consisted of a mixture of acetonitrile-water-diethylamine(65∶35∶0.03),with a flow rate set at 1.0 mL·min-1 and the column maintained at a temperature of 25℃.Results:NQAD analysis revealed a robust linear correlation between the concentration and the peak area for peimine within a concentration range of 2.450 to 1.470 μg·mL-1,achieving a correlation coefficient of 0.999 3.The limit of detection(LOD)and recovery rate for peimine were determined to be 14.70 ng and 99.50%(n=9),respectively.Similarly,a linear relationship was observed for peiminine between the concentration and the peak area,spanning a range of 3.657 to 1.170 μg·mL-1,with a correlation coefficient of 0.999 1.The LOD and recovery rate for peiminine were 21.94 ng and 100.5%(n=9),respectively.In contrast,ELSD yielded LOD of 24.50 ng for peimine and 36.57 ng for peiminine,with linear range of double logarithmic fitting was 4.900 to 490.0 μg·mL-1 and 7.314 to 585.1 μg·mL-1,respectively.Conclusion:NQAD outperforms ELSD in the quantification of peimine and peiminine,offering superior accuracy,precision,and sensitivity,along with an extended dynamic linear range.By enabling direct content calculation via linear regression,it streamlines the process,bypassing the complex double logarithmic calculations.This approach not only boosts the efficiency of data handling but also substantially simplifies the computational steps,addressing the detection and analysis needs for peimine and peiminine in huangshi xiangsheng pills.
3.A comparative study of NQAD and ELSD for the determination of peimine and peiminine in huangshi xiangsheng pills
Huiyi LIU ; Limin ZUO ; Xiaodan QIU ; Xin GUO ; Xiaofang LIAN ; Qingying JIA ; Yongsheng GU ; Xuanlin LIU ; Guangzhi SHAN
Drug Standards of China 2024;25(6):529-535
Objective:The study aimed to quantify the contents of peimine and peiminine in huangshi xiangsheng pills using a nano quantity analyte detector(NQAD)and compare the results with the evaporative light scattering detector(ELSD).Methods:Analytical separation was conducted utilizing a CAPCELL PAK MG Ⅲ C18 column(4.6 mm ×250 mm,5 μmi)as the stationary phase.The mobile phase consisted of a mixture of acetonitrile-water-diethylamine(65∶35∶0.03),with a flow rate set at 1.0 mL·min-1 and the column maintained at a temperature of 25℃.Results:NQAD analysis revealed a robust linear correlation between the concentration and the peak area for peimine within a concentration range of 2.450 to 1.470 μg·mL-1,achieving a correlation coefficient of 0.999 3.The limit of detection(LOD)and recovery rate for peimine were determined to be 14.70 ng and 99.50%(n=9),respectively.Similarly,a linear relationship was observed for peiminine between the concentration and the peak area,spanning a range of 3.657 to 1.170 μg·mL-1,with a correlation coefficient of 0.999 1.The LOD and recovery rate for peiminine were 21.94 ng and 100.5%(n=9),respectively.In contrast,ELSD yielded LOD of 24.50 ng for peimine and 36.57 ng for peiminine,with linear range of double logarithmic fitting was 4.900 to 490.0 μg·mL-1 and 7.314 to 585.1 μg·mL-1,respectively.Conclusion:NQAD outperforms ELSD in the quantification of peimine and peiminine,offering superior accuracy,precision,and sensitivity,along with an extended dynamic linear range.By enabling direct content calculation via linear regression,it streamlines the process,bypassing the complex double logarithmic calculations.This approach not only boosts the efficiency of data handling but also substantially simplifies the computational steps,addressing the detection and analysis needs for peimine and peiminine in huangshi xiangsheng pills.
4.Further Discussion on Legal Points in Ethical Review of Research Participants’ Informed Consent
Chinese Medical Ethics 2023;36(3):240-248
The protection of research participants’ rights and interests is mainly guaranteed through the informed consent system and the ethical review of the Ethics Committee. In practice, some sponsors or researchers misused or mixed legal terms when writing the informed consent forms. More importantly, during the implementation of informed consent by researchers, the phenomenon that insufficient and incomplete notification, and derogation of research participants’ specific rights and interests occurred. This not only affected the scientific nature of the research, but also violated the original intention of clinical trials or medical researchers, and did not fully respect the human dignity and value of research participants. It was urgent for the ethics committee to correct it during the ethical review, and urge the researchers or sponsors to correct and improve it in a timely manner.
5.Distribution characteristics of traditional Chinese medicine syndromes in 4 367 adult influenza patients: a Meta-analysis
Siyuan LEI ; Xuanlin LI ; Zhenzhen FENG ; Liu CHUN ; Jiansheng LI
Chinese Critical Care Medicine 2023;35(1):23-27
Objective:To systematically evaluate the distribution characteristics of traditional Chinese medicine (TCM) syndromes in adult influenza patients and to provide a basis for the TCM syndrome differentiation of influenza.Methods:The CNKI, CBM, Wanfang, VIP, PubMed, Embase, Cochrane Library databases were searched to collect cross -sectional studies on the distribution pattern of TCM syndromes in adult patients with influenza. The risk of bias assessment tool for cross -sectional studies developed by the Joanna Briggs Institute (JBI) evidence -based health care center was used to evaluate the literature quality, and the Stata 15.1 software was used to conduct a Meta -analysis of the pooled effect sizes of the included studies. Results:A total of 11 studies with 4 367 influenza patients were included. Quality assessment results of JBI showed that the risk bias was higher in the sample size calculation, and the description of sampling modalities and response rate was unclear. There were 17 influenza syndromes after specification, and a single group rate Meta -analysis was performed of the syndromes with ≥ 50 incident cases showed that there were 9 syndromes with an incidence ≥ 10% and statistical significance, the top 5 syndromes were syndrome of wind and heat invading the defense [ n = 1 583, RATE = 34.3%, 95% confidence interval (95% CI) was 22.2%-46.3%], syndrome of exterior cold and interior heat ( n = 1 122, RATE = 36.1%, 95% CI was 21.2%-51.1%), syndrome of wind -cold fettering the exterior ( n = 860, RATE = 19.4%, 95% CI was 10.7%-28.0%), syndrome of heat and toxin in the lung ( n = 217, RATE = 17.1%, 95% CI was 9.1%-25.0%), and syndrome of disease involving both defense phase and qi phase ( n = 184, RATE = 38.8%, 95% CI was 14.2%-63.5%). The results of the subgroup analysis in different geographical regions showed that the frequency of distribution of syndrome of wind and heat invading the defense and heat and toxin in the lung was higher in the South (RATE: 36.5%, 18.6%) than in the North (RATE: 30.9%, 15.4%), and the frequency of distribution of syndrome of wind -cold fettering the exterior and exterior cold and interior heat in the North (RATE: 23.8%, 40.1%) was higher than that in the South (RATE: 15.7%, 32.3%). Conclusions:There are 9 common TCM syndromes of influenza, including wind and heat invading the defense syndrome, exterior cold and interior heat syndrome, wind -cold fettering the exterior syndrome, heat and toxin in the lung syndrome, disease involving both defense phase and qi phase syndrome, wind and heat complicated by dampnessinvading the surface syndrome, wind and cold complicated by dampnessinvading the surface syndrome, defense phase syndrome and dampness and heatinvading the surface syndrome, which can provide a reference for the TCM syndrome differentiation and treatment of influenza.
6.Legal Points in Ethical Review of Subjects’ Informed Consent
Chinese Medical Ethics 2022;35(11):1188-1195
Subjects’ informed consent are needed in biomedical research, which has been confirmed by the Civil Code of the People’s Republic of China, Law of the People’s Republic of China on the Promotion of Basic Medical and Health Care, and Law on Doctors of the People’s Republic of China. Due to the professionalism and complexity of the law, researchers often have deficiencies in the use of legal terms, the fulfillment of disclosure obligations and the protection of subjects’ rights and interests when writing informed consent forms. When the ethics committee conducts ethical review on the informed consent form of the subjects, there are some problems such as lack of objective ability or insufficient subjective attention to the above shortcomings of the researchers. By combing the legal points, this paper summarized the correction scheme to provide reference for ethical review.
7.Evaluation of the efficacy and safety of human coagulation factor Ⅷ in the treatment of hemophilia A patients
Ruyi CHEN ; Yan WU ; Yiyun LIU ; Mingxia HOU ; Qingshuang SONG ; Xuanlin ZHONG ; Xueyun WANG ; Wenjie XIE ; Caiping GUO ; Zhan ZHANG ; Yunjia ZHANG
Chinese Journal of Blood Transfusion 2022;35(12):1220-1225
【Objective】 To evaluate the efficacy and safety of human coagulation factor Ⅷ developed by Shenzhen Weiguang Biological products Co, Ltd in the treatment of patients with hemophilia A. 【Methods】 A prospective, multi-center, open, single-group clinical study was conducted. A total of 65 subjects with hemophilia A were enrolled, and human coagulation factor Ⅷ(FⅧ) was injected according to the patients’ bleeding severity. The improvement score of bleeding symptoms and signs after the first infusion of the first bleeding event and the transfusion efficiency of FⅧ activity at 10 min and 1 hour after infusion were taken as the main efficacy indexes. The improvement scores of bleeding symptoms and signs after the first infusion and the increase of FⅧ activity at 10 min and 1 hour after infusion were the secondary efficacy indexes. 【Results】 The 65 subjects were enrolled in safety analysis set (SS) and full analysis set (FAS), and 58 of them were enrolled in protocol analysis set (PPS). Ten minutes and one hour after the first infusion, the level of factor Ⅷ activity in the subjects increased significantly, and the FⅧ activity increased by 100% or more in more than 79% of the subjects. The average infusion efficiency of FⅧ activity in all subjects was more than 100%. In 70% of the subjects, the pain was relieved rapidly and /or the bleeding symptoms were significantly improved 8 hours after each bleeding infusion, and the improvement rate of bleeding symptoms and signs reached 100% 72 hours after infusion. 【Conclusion】 After infusion of human coagulation factor Ⅷ, the activity level of factor Ⅷ in patients with hemophilia A significantly increased. The infusion efficiency can reach a optimal level, and the bleeding symptoms can be significantly improved.
8.A multicenter phase Ⅲ clinical study of human prothrombin complex concentrate in treatment of hemophilia B
Wei ZHANG ; Yirun LIU ; Yan WU ; Xuanlin ZHONG ; Qingshuang SONG ; Shitao CHEN ; Xueyun WANG ; Caiping GUO ; Zhan ZHANG ; Yunjia ZHANG
Chinese Journal of Blood Transfusion 2022;35(9):915-919
【Objective】 To evaluate the clinical efficacy and safety of one kind of human prothrombin complex concentrate in treatment of patients with hemophilia B. 【Methods】 The clinical data of 36 patients with hemophilia B treated with human prothrombin complex concentrate produced by Shenzhen Weiguang Biological Products Co. Ltd. from May 2018 to April 2019 were retrospectively analyzed, and its clinical efficacy and safety were analyzed. 【Results】 A total of 35 subjects entered the full analysis set (FAS)and safety set (SS), 33 subjects entered the per protocol Set (PPS). Thirty minutes after the first infusion of FAS subjects, the activity of coagulation factor Ⅸ increased from (3.93±0.975) IU/dL to (25.61±9.337) IU/dL, and the infusion efficiency was (96.43±22.007)%. The increased value of coagulation factor Ⅱ activity was (73.25±14.874) IU/dL. The activity of coagulation factor Ⅶ was (42.79±16.847) IU/dL. The increased value of coagulation factor Ⅹ activity was (65.29±17.042) IU/dL. The increased value of coagulation factor Ⅸ activity was (21.68±9.434%) IU/dL. Twenty-four hours after the first infusion of FAS subjects, the improvement of bleeding symptoms and signs was excellent in 21 cases (60%), improved in 14 cases (40.0%), and the effective rate was 100%. The incidence of adverse reactions was 2.9%(1/35), and there was no antibody to human coagulation factor Ⅸ and new virus infection. 【Conclusion】 Infusion of human prothrombin complex concentrate produced by Shenzhen Weiguang Biological Products Co. Ltd. in the treatment of hemophilia B has significant clinical efficacy and good safety.
9.Clinical application value of blastocysts derived from poor-quality embryos after day 3 transplantation and frozen
Li LIU ; Xiaomin CAO ; Xuanlin ZHANG ; Jianyong DI ; Yuanyuan WANG ; Fengqin XU
Chinese Journal of Reproduction and Contraception 2021;41(4):313-319
Objective:To evaluate the clinical value of blastocysts derived from poor-quality embryos after day 3 (D3) transplantation and frozen, to investigate the best embryo strategies of frozen-thawed blastocysts.Methods:A retrospective cohort study was conducted on 362 frozen-thawed blastocyst transfer cycles were retrospectively analyzed in the Department of Reproductive Medicine, Tianjin First Central Hospital from July 2015 to March 2020. According to the days of culture, they were divided into day 5 (D5) and day 6 (D6) blastocyst transplantation group; according to the number of embryos transferred, they were divided into single blastocyst transplantation group and double blastocyst transplantation group; according to the embryo quality, single blastocyst transplantation group was divided into single high-quality embryo group and single poor-quality embryo group. The double blastocyst transplantation group was divided into double high-quality blastocyst group, a high-quality embryo matching a poor-quality blastocyst transplantation group and the double poor-quality blastocyst group. Clinical pregnancy rate, implantation rate and multiple pregnancy rate were compared in each group.Results:The clinical pregnancy rate and the implantation rate of D5 blastocyst transplantation group in thawing cycles were higher than those of D6 blastocyst transplantation group [62.96% (102/162) vs. 42.50%(85/200), 53.98% (122/226) vs. 35.86% (104/290)](all P<0.001), and there was no statistically significant difference of early abortion rate and multiple pregnancy rate between the D5 and D6 groups ( P>0.05). There was no statistically significant difference in the clinical pregnancy rate and the early abortion rate of D5 single blastocyst groups and double blastocyst pregnancy ( P>0.05), the implantation rate of single blastocyst group was higher than that of the double blastocyst group [62.24% (61/98) vs. 47.66% (61/128)] while the multiple pregnancy rate of single blastocyst group was lower than that of the double blastocyst group [3.28% (2/61) vs. 46.34% (19/41)] ( P=0.029, P<0.001). The clinical pregnancy rate and the multiple pregnancy rate of D6 single blastocyst group were lower than those of D6 double blastocyst pregnancy group [35.45% (39/110) vs. 51.11% (46/90), 5.13% (2/39) vs. 26.09% (12/46)] ( P=0.026, P=0.009), there were no statistically significant differences in implantation rate and early abortion rate (all P>0.05). There were no statistically significant differences in clinical pregnancy rate, implantation rate, early abortion rate and multiple pregnancy rate between single high-quality embryo and poor-quality embryo group in D5 and D6 single blastocyst transplantation group (all P>0.05). There were no statistically significant differences in clinical pregnancy rate, implantation rate, early abortion rate, and multiple pregnancy rate of the double high-quality blastocyst transplantation group, a high-quality embryo matching a poor-quality blastocyst transplantation group and the double poor-quality blastocyst group in D5 ( P>0.05). The implantation rate of D6 double poor-quality embryo group [26.67% (24/90)] was lower than that of the double high-quality embryo group [47.62% (20/42)] and a high-quality embryo matching a poor-quality embryo group [43.75% (7/16)]( P=0.029), while there were no statistically significant differences in clinical pregnancy rate, early abortion rate, and multiple pregnancy rate (all P>0.05). Conclusion:After the high-quality D3 embryo transfer and freezing, the remaining poor-quality embryos can be cultured to form blastocyst, better clinical pregnancy rate was obtained for transfer the frozen-thawed blastocysts, it increases the value of embryos and reduces the cost of treatment. The quality of D5 blastocyst is better than that of D6 blastocyst. The single blastocyst transplantation of D5 is preferred to reduce the rate of multiple pregnancy without affecting the clinical pregnancy rate.
10.Clinical application value of blastocysts derived from poor-quality embryos after day 3 transplantation and frozen
Li LIU ; Xiaomin CAO ; Xuanlin ZHANG ; Jianyong DI ; Yuanyuan WANG ; Fengqin XU
Chinese Journal of Reproduction and Contraception 2021;41(4):313-319
Objective:To evaluate the clinical value of blastocysts derived from poor-quality embryos after day 3 (D3) transplantation and frozen, to investigate the best embryo strategies of frozen-thawed blastocysts.Methods:A retrospective cohort study was conducted on 362 frozen-thawed blastocyst transfer cycles were retrospectively analyzed in the Department of Reproductive Medicine, Tianjin First Central Hospital from July 2015 to March 2020. According to the days of culture, they were divided into day 5 (D5) and day 6 (D6) blastocyst transplantation group; according to the number of embryos transferred, they were divided into single blastocyst transplantation group and double blastocyst transplantation group; according to the embryo quality, single blastocyst transplantation group was divided into single high-quality embryo group and single poor-quality embryo group. The double blastocyst transplantation group was divided into double high-quality blastocyst group, a high-quality embryo matching a poor-quality blastocyst transplantation group and the double poor-quality blastocyst group. Clinical pregnancy rate, implantation rate and multiple pregnancy rate were compared in each group.Results:The clinical pregnancy rate and the implantation rate of D5 blastocyst transplantation group in thawing cycles were higher than those of D6 blastocyst transplantation group [62.96% (102/162) vs. 42.50%(85/200), 53.98% (122/226) vs. 35.86% (104/290)](all P<0.001), and there was no statistically significant difference of early abortion rate and multiple pregnancy rate between the D5 and D6 groups ( P>0.05). There was no statistically significant difference in the clinical pregnancy rate and the early abortion rate of D5 single blastocyst groups and double blastocyst pregnancy ( P>0.05), the implantation rate of single blastocyst group was higher than that of the double blastocyst group [62.24% (61/98) vs. 47.66% (61/128)] while the multiple pregnancy rate of single blastocyst group was lower than that of the double blastocyst group [3.28% (2/61) vs. 46.34% (19/41)] ( P=0.029, P<0.001). The clinical pregnancy rate and the multiple pregnancy rate of D6 single blastocyst group were lower than those of D6 double blastocyst pregnancy group [35.45% (39/110) vs. 51.11% (46/90), 5.13% (2/39) vs. 26.09% (12/46)] ( P=0.026, P=0.009), there were no statistically significant differences in implantation rate and early abortion rate (all P>0.05). There were no statistically significant differences in clinical pregnancy rate, implantation rate, early abortion rate and multiple pregnancy rate between single high-quality embryo and poor-quality embryo group in D5 and D6 single blastocyst transplantation group (all P>0.05). There were no statistically significant differences in clinical pregnancy rate, implantation rate, early abortion rate, and multiple pregnancy rate of the double high-quality blastocyst transplantation group, a high-quality embryo matching a poor-quality blastocyst transplantation group and the double poor-quality blastocyst group in D5 ( P>0.05). The implantation rate of D6 double poor-quality embryo group [26.67% (24/90)] was lower than that of the double high-quality embryo group [47.62% (20/42)] and a high-quality embryo matching a poor-quality embryo group [43.75% (7/16)]( P=0.029), while there were no statistically significant differences in clinical pregnancy rate, early abortion rate, and multiple pregnancy rate (all P>0.05). Conclusion:After the high-quality D3 embryo transfer and freezing, the remaining poor-quality embryos can be cultured to form blastocyst, better clinical pregnancy rate was obtained for transfer the frozen-thawed blastocysts, it increases the value of embryos and reduces the cost of treatment. The quality of D5 blastocyst is better than that of D6 blastocyst. The single blastocyst transplantation of D5 is preferred to reduce the rate of multiple pregnancy without affecting the clinical pregnancy rate.

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