1.Research progresses of endogenous vascular calcification inhibitor BMP-7
Xin ZHOU ; Lu XING ; Peng-Quan LI ; Dong ZHAO ; Hai-Qing CHU ; Chun-Xia HE ; Wei QIN ; Hui-Jin LI ; Jia FU ; Ye ZHANG ; Li XIAO ; Hui-Ling CAO
Chinese Pharmacological Bulletin 2024;40(7):1226-1230
Vascular calcification is a highly regulated process of ectopic calcification in cardiovascular system while no effective intervention can be clinically performed up to date.As vascular calcification undergoes a common regulatory mechanism within bone formation,bone morphogenetic protein 7(BMP-7)main-tains contractile phenotype of vascular smooth muscle cells and further inhibits vascular calcification via promoting the process of osteoblast differentiation,reducing ectopic calcification pressure by increasing bone formation and reducing bone resorption.This work systematically reviews the role of BMP-7 in vascular calcifi-cation and the possible mechanism,and their current clinical application as well.The current proceedings may help develope early diagnostic strategy and therapeutic treatment with BMP-7 as a new molecular marker and potential drug target.The expec-tation could achieve early prevention and intervention of vascular calcification and improve poor prognosis on patients.
2.A multicenter clinical study on the treatment of lateral epicondylitis of humerus by manipulation
Xiao-Zhou HOU ; Jing YIN ; Hai-Yang WANG ; Jin-Yu GU ; Tian-Hao WAN ; Man-Hong YANG ; Di XIA ; Qing ZHANG
China Journal of Orthopaedics and Traumatology 2024;37(3):251-257
Objective To investigate clinical effect of tendons pulling,poking and kneading for the treatment of external humeral epicondylitis.Metods From January 2018 to December 2021,a multicenter randomized controlled study was per-formed to collect 192 patients with external humeral epicondylitis in Wangjing Hospital,Beijing Dianli Hospital,and Beijing Fengsheng Osteotraumatology Hospital,respectively,and they were divided into treatment group and control group by random number table method.There were 96 patients in treatment group,including 36 males and 60 females,aged from 28 to 60 years old with an average of(41.20±5.50)years old;the course of disease ranged from 1 to 14 days with an average of(5.24±1.35)days;they were treated once every other day for 2 weeks.There were 96 patients in control group,including 33 males and 63 females,aged from 26 to 60 years old with an average of(43.35±7.75)years old;the course of disease ranged from 1 to 14 days with an average of(5.86±1.48)days;they were treated with topical voltaalin combined with elbow joint fixation for 2 weeks.Visual analogue scale(VAS)and Hospital for Surgery Scoring System(HSS)elbow pronation and supination angles,wrist metacarpal flexion and dorsal extension angles,elbow tenderness between two groups were compared before treatment and at 1,3,5,7,11 and 13 days after treatment;Hospital for Surgery Scoring System 2(HSS2)was compared before treatment and the final treatment.Results All patients were followed up for 10 to 14 days with an average of(12±1.6)days.VAS between treatment group and control group before treatment were 6.83±1.36 and 6.79±1.58,respectively,and decreased to 1.49±1.09 and 2.11±1.81 after the final treatment.VAS of treatment group were significantly lower than those of control group at 1,3,5,7,9,11 and 13 days after treatment(P<0.05).HSS between two groups were 61.73±11.00 and 36.47±12.45 before treatment,respectively,and increased to 94.42±5.9 and 91.44±9.11 at the final treatment.HSS of treatment group were signifi-cantly higher than those of control group at 1,3,5,7,9,11 and 13 days after treatment(P<0.05).On the 5th day after treat-ment,the external and internal rotation angles of elbow in treatment group were(66.41±12.69)° and(66.35±13.54)°,while those in control group were(62.08±16.03)° and(61.77±16.35)°.On the 7th day after treatment,the external and internal ro-tation angles of elbow were(69.79±12.64)° and(70.02±13.55)° in treatment group,and(65.28±15.86)° and(65.09± 16.67)° in control group.Elbow joint motion in treatment group was higher than that in control group(P<0.05).On the 5th day after treatment,angles of wrist dorsiflexion and palm flexion were(39.43±15.94)°and(46.68±11.10)° in treatment group,and(38.51±18.49)° and(44.27±13.58)° in control group.On the 7th day after treatment,angles of wrist dorsiflexion and palm flexion were(42.52±16.50)° and(49.23±10.96)° in treatment group,and(41.18±20.09)° and(46.64±14.63)° in control group.The motion of wrist joint in treatment group was higher than that in control group(P<0.05).On the 13th day after treatment,HSS2 in treatment group 93.61±6.32 were higher than those in control group 92.06±7.94(P<0.05).There was no significant difference in elbow tenderness between two groups at each time point(P>0.05).Conclusion Voltaren external treatment combined with elbow fixation and tendons pulling,poking and kneading could effectively improve symptoms of exter-nal humeral epicondylitis.Compared with voltaren external treatment,tendons pulling,poking and kneading has advantages of longer analgesic time and better elbow function recovery.
3.Optimized expression of the diphtheria toxin mutant CRM197 in Escherichia coli and population analysis of serum antibody levels
Xiao-Li CHEN ; Yi-Xin GU ; Hai-Rui WANG ; Gui-Lan ZHOU ; Xin ZHANG ; Chang LIU ; Jian-Zhong ZHANG ; Zhu-Jun SHAO ; Mao-Jun ZHANG
Chinese Journal of Zoonoses 2024;40(5):430-434
A prokaryotic expression vector for the mutant diphtheria toxin CRM197 was constructed and expressed in Esch-erichia coli cells.Anti-CRM197 antibody concentrations were detected in serum samples of healthy volunteers.The crm 197 gene was codon-optimized in E.coli and cloned into the plasmid pET28a(+)under optimized expression conditions.CRM197 was purified using Ni-NTA spin columns and ion exchange chromatography,and confirmed by western blot analysis.The puri-fied CRM197 was used to detect specific anti-CRM197 antibody levels in serum samples of different age groups.The results showed that soluble codon-optimized CRM197 was successfully expressed under optimized expression conditions.The purity of CRM197 was more than 95%,as determined with Ni-NTA spin columns and ion exchange chromatography,consistent with the single specific bands obtained by western blot analysis and detection of serum levels of the anti-CRM197 antibody.Collec-tively,these results confirmed that the proposed expression strategy achieved high-yield production of soluble CRM197,al-though high levels in human serum may affect evaluation of immune interactions with glycan-CRM197 conjugates for applica-tion as a diagnostic antigen.The diphtheria mutant toxin CRM197 is used in many conjugate vaccines.The synthetic crm 197 gene with codon optimization in pET28a was transformed into E.coli Origami B(DE3)cells.CRM197 was induced by isopro-pyl β-d-1-thiogalactopyranoside and high level accumulation of soluble CRM197 was purified using Ni-NTA spin columns and ion exchange chromatography.The purity of the final prepara-tion reached 95%.CRM197 was used to detect the concentra-tions of the anti-CRM197 antibody in serum samples of healthy volunteers of different ages.The proposed expression strategy yielded high production of CRM197,which could interfere with evaluations of induced immune interactions by glycan-CRM197 conjugates and prohibit application as a diagnostic antigen.
4.Characteristic Analysis of Adult Acute Myeloid Leukemia Patients with PTPN11 Gene Mutation
Li SHENG ; Ya-Jiao LIU ; Jing-Fen ZHOU ; Hong-Ying CHAO ; Hai-Ying HUA ; Xin ZHOU ; Xiao-Hong ZHAO
Journal of Experimental Hematology 2024;32(4):1063-1070
Objective:To investigate the incidence of PTPN11 gene mutation and its associated gene mutations in adult patients with acute myeloid leukemia(AML),and analyze its clinical characteristics.Methods:Second-generation sequencing and Sanger sequencing were used to detect 51 gene mutations,and multiplex-PCR was used to detect 41 fusion genes from 451 newly diagnosed adult AML patients admitted to Affiliated Hospital of Jiangnan University,Changzhou Second People's Hospital,Wuxi People's Hospital and Wuxi Second People's Hospital from January 2017 to July 2022.Results:Among 451 primary adult AML patients,the PTPN11 gene mutation was detected in 34 cases,and the mutation rate was 7.5%.In the 34 patients,37 PTPN11 alterations were found,which were exclusively missense mutations affecting residues located within the N-SH2(31 cases)and PTP(6 cases)domains and clustered overwhelmingly in exon 3.The platelet count of PTPN11 mutation patients was 76.5(23.5,119.0)× 109/L,which was significantly higher than 41.0(22.0,82.5)×109/L of wild-type patients(P<0.05).While,there were no significant differences in sex,age,peripheral white blood cell count,hemoglobin,and bone marrow blast between PTPN11 mutation and wild-type patients(P>0.05).In FAB subtypes,PTPN11 mutations were mainly distributed in M5,followed by M2 and M4,less frequently in M3 and M6.There was no significant difference in the distribution of FAB subtypes between PTPN11 mutation and wild-type patients(P>0.05).A total of 118 AML patients were detected positive fusion gene,among which patients with PTPN11 mutations had a higher incidence of positive MLL-AF6 than wild-type ones(P<0.01).97.1%of 34 patients with PTPN11 mutations were accompanied by other mutations,in descending order,they were respectively NPM1(38.2%),NRAS(32.4%),FLT3-ITD(32.4%),DNMT3A(32.4%)and KRAS(23.5%),etc.Conclusion:PTPN11 mutation has a certain incidence in AML patients and is clustered overwhelmingly in exon 3.ALL of them are exclusively missense mutations,and most often present in conjunction with NPM1 mutations.FAB typing of PTPN11 mutation is mostly manifested as M5 subtype,which is associated with higher platelet counts.
5.Development of biological safety protection third-level laboratory based on folding-modular shelters
Si-Qing ZHAO ; Jian-Qiao XIA ; Zhong-Jie SUN ; Kang OUYANG ; Xiao-Jun JIN ; Kang-Li ZHOU ; Wei XIE ; Hai-Yang LI ; Da-Peng JIANG ; Yan-Yan GAO ; Bei SUN
Chinese Medical Equipment Journal 2024;45(3):41-46
Objective To develop a biological safety protection third-level(BSL-3)laboratory based on folding-modular shelters to solve the problems of the existing laboratories in space and function expansion,large-scale deployment and low-cost transportation.Methods The BSL-3 laboratory was composed of a folding combined shelter module,a ventilation and purification module,a power supply and distribution module,a monitoring and communication module,a control system module and an equipment module.The folding combined shelter module used a leveling base frame as the foundation and a lightweight panel as the enclosure mechanism,and was divided into an auxiliary area and a protection protected area;the ventilation and purification module was made up of an air supply unit and an air exhaust unit,the air supply unit was integrated with a fresh-air air conditioner and the exhaust unit was equipped with a main fan,a standby fan and a bag in/bag out filter;the control system module adopted a supervision mode of decentralized control and centralized management,which executed communication with the data server as the center and Profinet protocol and MODBUS-TCP.Results The BSL-3 laboratory proved to meet the requirements of relevant standards in internal microenvironment,airflow direction,airtightness,working condition and disinfection effect.Conclusion The BSL-3 laboratory is compatible with large-scale transport and deployment and facilitates reliable and safe experiments for epidemic prevention and control and cross-regional support.[Chinese Medical Equipment Journal,2024,45(3):41-46]
6.Design of portable collection device for exhaled breath condensate
An XIANG ; Lei ZHOU ; Qi-Feng JI ; Yuan-Zhe LI ; Qin WANG ; Shi-Man ZHU ; Jie PENG ; Xiao-Ying LEI ; Wei-Na LI ; Li WANG ; Yan-Hai GUO ; Zi-Fan LU
Chinese Medical Equipment Journal 2024;45(8):32-37
Objective To develop a portable collection device of human exhaled breath condensate(EBC)based on natural breathing to meet the needs for rapid screening of human respiratory tract(especially lower respiratory tract)infections.Methods The device consisted of a refrigeration unit,a heat dissipation unit and a condensation unit.The refrigeration unit adopted a TES1-7102 thermoelectric Peltier cooler semiconductor as the refrigeration element;the heat dissipation unit was composed of a high thermal conductivity aluminum heat sink and a high-speed brushless cooling fan;the condensation unit was made up of a cold guide plate and a condenser,in which the cold guide plate was made of thin sheet of aluminum alloy,and the condenser was prepared by 3D printing technology and made of hydrophobic polylactic acid,with primary and secondary 2-stage guide grooves and an ultra-thin condensing surface.The performance of the device was verified in terms of cooling,thermal conductivity,condensation and human EBC collection and content analysis.Results Performance analysis showed that after refrigeration began the temperature difference between the condenser surface and the exhaled gas met the requirements of the condenser,and no obvious thermal resistance was found on the condensing surface so that large droplets could be formed rapidly and then be collected after the gas-liquid phase change of the exhaled gas on the condensing surface.Human EBC collection and content analysis indicated the device realized home self-collection of EBCs from people of all ages,and the concentrations of interleukins,C-reactive protein and other inflammation-related indexes and the pH value of the collected EBC samples were all correlated with respiratory infections in the subjects.Conclusion The device developed with easy operation avoids the discomfort of blowing collection and the risk of saliva contamination,and is worthy promoting for rapid diagnosis and dynamic monitoring of respiratory tract infection and other related diseases.[Chinese Medical Equipment Journal,2024,45(8):32-37]
7.Effect of hand hygiene intervention on healthcare-associated case infection incidence from 2014 to 2022
Jia-Yan DING ; Rui-Hong SHEN ; Wen-Qin ZHOU ; Ya-Yun YUAN ; Mei HUANG ; Ya YANG ; Bing-Chao CAI ; Hai-Qun BAN ; Xiao-Fang FU
Chinese Journal of Infection Control 2024;23(2):208-213
Objective To observe the effect of multi-modal hand hygiene(HH)intervention on HH compliance,as well as the relationship between HH compliance and the healthcare-associated(HA)case infection incidence.Methods From 2014 to 2022,the infection control team in a tertiary first-class hospital implemented multi-modal HH intervention for health care workers(HCWs).The changing trend of HH monitoring data,the correlation be-tween HH compliance rate and HA case infection incidence were analyzed retrospectively.Results The consump-tion of HH products in the wards showed a stable upward trend;HH compliance rate increased from 64.98%in 2014 to 85.01%in 2022(P<0.001),and HA case infection incidence decreased from 1.21%to 0.83%(P<0.05).HH compliance rate was negatively correlated with HA case infection incidence(r=-0.369,P=0.027).HH compliance rates in different regions and job posts in each quarter were increased(P<0.001).For 5 different HH moments in each quarter,HH compliance rate fluctuated slightly before sterile manipulation and after touching patient;presented rising trend after touching surroundings around patient,and decreased before touching patient and after touching patient's body fluid since 2020(P<0.001).Conclusion Multi-modal HH intervention can im-prove the HH compliance of HCWs,improving their HH awareness is conducive to reducing HA case infection incidence.
8.Analysis of prostate transcriptome landscape characteristics in benign prostate hyperplasia patients taking finasteride
Lang ZHOU ; Ke LIU ; Min LU ; Hai BI ; Xiao HUO ; Lulin MA ; Cheng LIU
Journal of Modern Urology 2024;29(2):101-107
【Objective】 To explore the effects of finasteride on the gene expression in patients with benign prostatic hyperplasia (BPH) through transcriptome analysis. 【Methods】 Postoperative prostate tissues from patients who underwent prostatectomy at Peking University Third Hospital during Oct.2020 and Oct.2021 were collected.The patients were divided into medication group and non-medication group based on whether they had taken finasteride for a long time before surgery, with 8 patients in either groups.Transcriptome sequencing analysis was performed and the results were validated with qPCR and immunohistochemistry analysis. 【Results】 Compared with the non-medication group, 857 up-regulated and 806 down-regulated genes were screened in the medication group.Pathway enrichment analysis showed that finasteride induced down-regulation of vascular endothelial growth factor D (VEGFD) expression in the focal adhesion pathway.Inter group network analysis suggested that the calcium signaling pathway was key in the entire process.GSEA enrichment analysis further revealed the up regulation of CD38 gene expression in the calcium signaling pathway.The qPCR and immunohistochemistry analysis supported the transcriptome results mentioned above, and found that androgen receptor (AR) expression was also increased. 【Conclusion】 Finasteride reduces prostate microvascular formation by downregulating the expression of VEGFD in the focal adhesion pathway, thereby reducing the risk of bleeding during prostate hyperplasia surgery. Long-term use of finasteride leads to the up regulation of CD38 expression in the calcium signaling pathway, which may lead to the development of finasteride resistance.
9.Effect of Simo decoction on the regulation of NLRP3/Caspase-1/GSDMD signal pathway on duodenal microinflammation in rats with functional dyspepsia
Qin LIU ; Xiao-Yuan LIN ; Ling-Feng YANG ; Qian LUO ; Yun-Zong HAN ; Si-Qing CHEN ; Hai-Yue ZHANG ; Shu ZHOU ; Sai-Nan ZHOU
The Chinese Journal of Clinical Pharmacology 2024;40(1):67-71
Objective To investigate the effects of Simo decoction on duodenal microinflammation and NOD-like receptor thermal protein domain associated protein 3(NLRP3)/cysteinyl aspartate-specific proteinase-1(Caspase-1)/gasdermin D(GSDMD)signaling pathway in rats with functional dyspepsia(FD).Methods The FD model was established by multifactorial method.SD rats were randomly divided into normal group,model group(FD model),positive control group(gavage administration of 0.305 mg·kg-1 mosapride injection)and experimental-H,-M,-L groups(gavage administration of 5.62,2.81,1.40 g·kg-1 Simo decoction).Small intestinal advancement rate and gastric emptying rate was determined;the levels of interleukin(IL)-1 β and IL-18 in serum were determined by enzyme linked immunosorbent assay(ELISA);the protein expression of NLRP3 and GSDMD in duodenal tissue was detected by Western blotting.Results The gastric emptying rates of normal,model,positive control and experimental-H,-M,-Lgroupswere(58.34±5.72)%,(29.16±8.37)%,(48.77±6.10)%,(48.35±6.04)%,(48.20±3.49)%and(39.24±4.20)%;the small intestinal propulsion rates were(82.01±7.55)%,(41.95±9.53)%,(64.61±10.18)%,(75.04±9.76)%,(60.58±7.13)%and(45.89±7.40)%;serum IL-1 β expression were(12.86±0.88),(43.73±4.60),(18.84±0.86),(24.61±1.57),(19.14±0.77)and(29.04±0.72)pg·mL-1;IL-18 expressions were(95.00±3.74),(170.60±8.78),(108.50±3.05),(118.90±3.45),(99.90±8.70)and(141.00±3.71)pg·mL-1;the relative expression levels of NLRP3 proteins were 0.32±0.02,0.84±0.05,0.42±0.03,0.48±0.02,0.61±0.04 and 0.62±0.05;the relative expression levels of GSDMD proteins were 0.34±0.05,0.93±0.06,0.35±0.03,0.52±0.02,0.53±0.06 and 0.55±0.05,respectively.Compared with the normal group,the above indexes in the model group have statistical significance;compared with the model group,the above indexes in the experimental-H group and the positive control group also have statistical significance(P<0.01 or P<0.05).Conclusion Simo decoction can effectively improve the general condition and duodenal microinflammation in FD rats,and the mechanism may be related to the inhibition of duodenal NLRP3/Caspase-1/GSDMD signaling pathway.
10.Discussion of the methodology and implementation steps for assessing the causality of adverse event
Hong FANG ; Shuo-Peng JIA ; Hai-Xue WANG ; Xiao-Jing PEI ; Min LIU ; An-Qi YU ; Ling-Yun ZHOU ; Fang-Fang SHI ; Shu-Jie LU ; Shu-Hang WANG ; Yue YU ; Dan-Dan CUI ; Yu TANG ; Ning LI ; Ze-Huai WEN
The Chinese Journal of Clinical Pharmacology 2024;40(2):299-304
The assessment of adverse drug events is an important basis for clinical safety evaluation and post-marketing risk control of drugs,and its causality assessment is gaining increasing attention.The existing methods for assessing the causal relationship between drugs and the occurrence of adverse reactions can be broadly classified into three categories:global introspective methods,standardized methods,and probabilistic methods.At present,there is no systematic introduction of the operational details of the various methods in the domestic literature.This paper compares representative causality assessment methods in terms of definition and concept,methodological steps,industry evaluation and advantages and disadvantages,clarifies the basic process of determining the causality of adverse drug reactions,and discusses how to further improve the adverse drug reaction monitoring and evaluation system,with a view to providing a reference for drug development and pharmacovigilance work in China.

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