OBJECTIVE To study the effects of sophoranone （SOP） on the biological behavior of nasopharyngeal carcinoma CNE-1 cells and mitogen-activated protein kinase （MAPK） signaling pathway. METHODS CNE-1 cells were divided into blank group and SOP low-， medium- and high-concentration groups （SOP-L group， SOP-M group， SOP-H group， 25， 50 and 100 μmol/L）. The number of invasive cells， the number of migratory cells， and the apoptosis rate of cells were detected. The expression levels of mitogen-activated protein kinase kinase （MEK）， extracellular signal-regulated kinase 1 （ERK1）， ERK2， and c-Jun N-terminal kinase （JNK） mRNA， as well as phosphorylation levels of ERK， JNK， and p38 mitogen-activated protein kinase （abbreviated as “p38”） proteins in cells were all detected. Additionally， cells were divided into blank group， SOP high-concentration group （SOP- H group， 100 μmol/L）， SOP high-concentration combined with p38 inhibitor group （SOP-H+SB group， 100 μmol/L SOP+10 μmol/L SB）， and SOP high-concentration combined with JNK inhibitor group （SOP-H+SP group， 100 μmol/L SOP+10 μmol/L SP）. The number of invasive cells， cell migration rate， and the protein phosphorylation levels of JNK and p38 in cells， as well as the protein expression levels of matrix metalloproteinase-9（MMP-9）， proliferating cell nuclear antigen Ki67， and cleaved-caspase-3 were measured. RESULTS Compared with the blank group， SOP for each concentration could significantly decrease the number of invasive cells， the number of migratory cells， and mRNA expressions of MEK， ERK1， ERK2 （except for the SOP-L group） and JNK， but increase the apoptosis rate of cells and phosphorylation levels of ERK， JNK， and p38 proteins （P＜0.05）. Compared with the SOP-H group， the protein phosphorylation levels of p38 and JNK， and the protein expression of cleaved-caspase-3 were decreased significantly in SOP-H+SB group and SOP-H+SP group， while the number of invasive cells， cell migration rate， and the protein expression levels of MMP-9 and Ki67 were all increased significantly （P＜0.05）. CONCLUSIONS SOP can inhibit the proliferation， migration and invasion of CNE-1 cells， and induce the apoptosis， the mechanisms of which may be associated with promoting the phosphorylation of proteins related to the MAPK signaling pathway.

Objective To investigate the effect of Yiqi Huoxue Tongluo Decoction on microRNA-126a-5p(miR-126a-5p)and vascular endothelial growth factor(VEGF)signaling pathway in cervical spondylotic myelopathy model rats.Methods Thirty healthy male SD rats were divided into the sham operation group,the model group and the traditional Chinese medicine(TCM)group by random number table method.Cervical spondylotic myelopathy models were prepared in the model group and the TCM group.The TCM group was given intragastric administration of Yiqi Huoxue Tongluo Decoction,while the sham operation group and the model group were given intragastric administration of normal saline for 12 weeks.After intervention,the threshold of mechanical stimulation and retraction time of thermal stimulation in each group were measured by behavior tests.Rats were sacrificed to collect intervertebral disc tissue for hematoxylin-eosin(HE)staining and observe the number of vascular buds in intervertebral disc.Rat intervertebral disc annulus fibrosus cells were subjected to terminal dexynucleotidyl transferase-mediated dUTP nick end labeling(TUNEL)staining.The miR-126a-5p and VEGF mRNA of rat intervertebral disc tissue were detected by real-time fluorescence quantitative polymerase chain reaction(RT-PCR).The expression of VEGF protein of rat intervertebral disc tissue was detected by Western blot assay.Results Compared with the sham operation group,the number of vascular buds in intervertebral disc was decreased in the model group and the TCM group.The cell destruction of intervertebral disc annulus was obvious in rats,and apoptosis was high and cell density decreased.Mechanical stimulation threshold decreased,and mechanical stimulation threshold decreased.The level of miR-126a-5p was decreased,and the expression levels of VEGF mRNA and protein were increased.Compared with the model group,the number of vascular buds in intervertebral disc was increased in the TCM group.The destruction of intervertebral disc annulus cells was alleviated in rats.The apoptosis of annulus fibrosus cells in intervertebral disc decreased and cell density increased.The threshold of mechanical stimulation increased,and the retraction time of thermal stimulation was prolonged.The level of miR-126a-5p increased,and the expression levels of VEGF mRNA and protein decreased(P＜0.05).Conclusion The mechanism of Yiqi Huoxue Tongluo Decoction in the treatment of cervical spondylotic myelopathy may be related to the up-regulation of miR-126a-5p expression and the down-regulation of VEGF expression.

Objective: To construct a prediction model for preterm birth risk among pregnant women, so as to provide the reference for screening high-risk population and preventing preterm birth. Methods: Pregnant women who received antenatal examination and delivered at the Women's Hospital, School of Medicine, Zhejiang University from January 1 to December 31, 2019 were selected as the study subjects, among them, 80% were included in the modeling group, and 20% were included in the validation group. Demographic and clinical information were collected. A multivariable logistic regression model was used to analyze the predictive factors of preterm birth risk in the modeling group, and a preterm birth risk prediction model was established based on the OR values of predictive factors. The model was validated with the data from the validation group. The Youden index was used to determine the critical score for predicting preterm birth risk. The prediction performance of the model was evaluated using the receiver operating characteristic (ROC) curve. Results: A total of 15 197 pregnant women were surveyed, including 12 131 pregnant women in the observation group and 3 066 pregnant women in the validation group. There was no statistically significant difference in age, education level and gravidity between the two groups of pregnant women (all P<0.05). Multivariable logistic regression analysis identified the number of pregnancies, education level, place of residence, hypertension, diabetes, history of preterm birth, twin-pregnancy, placenta praevia, and gestational hypertension as risk prediction factors for preterm birth risk among pregnant women. The risk score system for preterm birth was established as follows: >2 pregnancies (2 points), high school education or below (4 points), college degree or above (-4 points), rural residence (5 points), hypertension (7 points), diabetes (11 points), history of preterm birth (11 points), twin-pregnancy (28 points), placenta previa (19 points), and gestational hypertension (12 points). The total score of the preterm birth risk scoring system ranged from -4 to 99 points. When the critical score was 8 points, the Youden index was the highest at 0.480, with an area under the ROC curve of 0.749 (95%CI: 0.732-0.767), a sensitivity of 0.610, and a specificity of 0.886, indicating good prediction performance of the model. Conclusion The preterm birth risk prediction model established in this study based on demographic and clinical characteristics of pregnant women can effectively predict the risk of preterm birth among pregnant women.

With the development of information technology, the massive growth of pharmaceutical electronic data and the significant increase in the reports of drug adverse event reports have brought great challenges to pharmacovigilance research. Data mining techniques can automatically extract the risk signals of adverse drug reaction from real-world data. Therefore, efficient data mining of massive adverse event reporting is a necessary measure to realize the automatic detection of adverse drug reactions. By introducing the current major large-scale adverse drug event reporting databases and related data mining methods, this study reviews the application and limitations of adverse drug reaction data mining technology in pharmacovigilance, which provides reference for pharmacovigilance-related institutions and researchers.

OBJECTIVE To investigate the preventive effect of cucurbitacin B （CB） on sepsis-induced acute lung injury （ALI） and its mechanism. METHODS The mice were divided into control group， model group， dexamethasone group （positive control， 2 mg/kg）， CB low-dose and high-dose groups （25， 50 mg/kg）. Each group was given relevant medicine intraperitoneally， once a day， for 3 consecutive days. Twenty-four hours after the last administration， those groups were given lipopolysaccharide （10 mg/kg） intraperitoneally to establish sepsis-induced ALI model （finally， 8 mice per group were included in the experiment）， except for control group. Twenty-four hours after medication， blood routine indicators （total white blood cell count， neutrophils count， lymphocytes count）， lung function indicators （total lung resistance， pulmonary outflow resistance， lung dynamic compliance， peak expiratory flow rate， and maximum ventilation volume）， dry wet ratio of lung tissue were measured in each group. The lung tissue level of myeloperoxidase （MPO）， and the serum levels of tumor necrosis factor-α （TNF-α）， interleukin 1β （IL-1β）， IL-6， superoxide dismutase （SOD） and malondialdehyde （MDA） were all detected. The pathological changes of lung tissue were observed； immunohistochemistry was used to detect the positive expression of phosphorylation signal transducer and activator of transcription 3 （p-STAT3） in the lung tissue. Western blot assay was used to detect the expressions of proteins related to IL-6/JAK2/ STAT3 signaling pathway in the lung tissue. RESULTS Compared with control group， total pulmonary resistance， pulmonary flow resistance， dry wet ratio of lung tissue， the total white blood cell count， neutrophils count， lymphocytes count of whole blood， the lung tissue level of MPO and serum levels of MDA， IL-6， IL-1β and TNF-α， the p-STAT3 protein optical density value， the protein expressions of IL-6 and IL-6 receptor， and the phosphorylation levels of JAK2 and STAT3 protein were increased significantly in the model group （P＜0.01）， while lung dynamic compliance， peak expiratory flow rate， maximum ventilation volume and serum level of SOD were decreased significantly （P＜0.05 or P＜0.01）. Pulmonary tissue showed alveolar collapse and infiltration of inflammatory cells. Compared with the model group， the above indexes of mice were reversed significantly in dexamethasone group and CB groups （P＜0.05 or P＜0.01）， the pathological damage of lung tissue was reduced. CONCLUSIONS CB can prevent sepsis-induced ALI by inhibiting the activity of Δ 基金项目遵义市科技计划项目（No.202252） IL-6/JAK2/STAT3 signaling pathway and relieving ＊第一作者主治医师。研究方向：重症医学。E-mail：fjuanxui@ 163.com inflammatory reactions. # 通信作者 主任医师。研究方向：儿童呼吸系统疾病诊断与治

Objective:To study the relationship between adult fluoride exposure and grip strength in rural areas of China with fluorosis, as well as the roles of basal metabolic rate (BMR) and body fat percentage (BFP) in the association between fluoride exposure and grip strength.Methods:From April to May 2017, a cluster sampling method was used to conduct a questionnaire survey, physical examination, and biological sample collection on residents aged 18 - 60 in Tongxu County, Kaifeng City, Henan Province (epidemic areas of drinking-water-borne fluorosis). A total of 1 168 subjects were included in the study, including 427 males and 741 females. The fluoride ion selective electrode method and the picric acid method were used to determine the concentrations of urine fluoride and urine creatinine, and the adjusted urine fluoride concentration (CUF) was calculated. BMR and BFP were measured by a bioelectrical impendence method, and the grip strength was measured by a Jamar grip dynamometer. The relationship between CUF, BMR, BFP and grip strength were analyzed using a generalized linear model regression. The mediation effect model was used to assess the mediating effect of BMR and BFP on the association between CUF and grip strength.Results:Female grip strength decreased by 0.28 kg ( P = 0.043) for every 1.00 mg/L increment in CUF. No similar association was found between the two in males ( P = 0.744). Regardless of gender stratification, BMR was positively correlated with grip strength ( P < 0.001). For every 1.00% increase in BFP, female grip strength decreased by 0.18 kg ( P = 0.043). The mediation effect model analysis results showed that the mediation effect ratios of BMR and BFP in the association between CUF and grip strength in female were 65.1% ( P < 0.001) and 8.4% ( P = 0.111), respectively. Conclusion:Fluoride exposure is associated with changes in female grip strength, and BMR changes play a partial mediating role in the association between fluoride exposure and female grip strength.

Objective:To demonstrate the polymorphism of α chain of bovine major histocompatibility complex(BoLA)classⅠmolecule and domain binding constant chain(Ii).Methods:Total 75 BoLA Iα genes were obtained from three Huaibei cattle and analyzed by molecular biology software;the genes of typical BoLA Iα domains and Ii were cloned,and then inserted into prokaryotic expression plasmid.After induced protein expression;the domains of BoLA Ⅰα chain binding to Ii were detected by pull-down meth-od and Western blot.The recombinant eukaryotic expression plasmids were constructed and the co-localization of BoLA Iα segments with Ii was observed by laser confocal microscopy.Results:Firstly,it was found that there were at least 5 kinds of BoLA Iα in the cloned gene sequence,which were highly polymorphic and they were mainly distributed in the antigen peptide binding region(PBR)of BoLA Ⅰ(α1α2)and cytoplasmic region.Secondly,the prokaryotic recombinant plasmids containing BoLA Ⅰα1α2α3,BoLA Ⅰα1α2 or BoLA Ⅰα 3 were constructed,then they were respectively induced to express and purified,in which,the BoLA Ⅰα1α2α3 and BoLA Ⅰα1α2 had the activity of binding to Ii.Finally,in 293T cells BoLA Ⅰα1α 2α3 or BoLA Ⅰα1α2 was found that could co-localize with Ii,while a single BoLA Ⅰα3 could not.Conclusion:BoLA Ⅰα gene is highly polymorphic.BoLA Ⅰα1α2 is a func-tional fragment that binds to Ii and co-locates intracellular.

Objective To investigate the efficacy and safety of Huoluoxiaolingdan formula combined with ginkgolide injection in the treatment of ischemic stroke patients with blood stasis blockage syndrome.Methods The ischemic stroke patients with blood stasis blockage syndrome who were treated in Suzhou First People's Hospital from June 2017 to August 2019 were randomly divided into test group and control group.The control group was given ginkgolide injection,and the test group was given Huoluoxiaolingdan formula additionally.Both groups were treated for 2 weeks.The efficacy and adverse drug reactions of the two groups were evaluated,and the changes of clinical scores,hemorheology,blood lipids and inflammatory factors before and after treatment were compared between the two groups.Results A total of 194 patients were included,there were 97 cases in each group.The total effective rate of test group was 91.75％,which was significantly higher than that of control group(79.38％)(P＜0.05),and the incidence of adverse reactions was significantly lower than that in the control group(P＜0.05).After treatment,NIHSS,CSS and ASS in both groups were lower than before treatment(P＜0.05),while BI was higher than before treatment(P＜0.05).The levels of ηp,ηb,Fib and EEP in test group were significantly lower than those in control group(P＜0.05).HDL-C level of test group was significantly higher than that of control group,TC,LDL-C and TG levels were lower than that of control group(P＜0.05).The levels of IL-4 in test group were significantly higher than those in control group,and the levels of IL-1 β,IL-8 and TNF-α were lower than those in control group(P＜0.05).The above indexes in the test group was significantly better than that in control group(P＜0.05).Conclusion Huoluoxiaolingdan formula combined with ginkgolide injection can significantly improve the efficacy of patients with blood stasis blockage syndrome during the recovery period of ischemic stroke,improve clinical symptom score,correct abnormal hemorheology,reduce blood lipid level,inhibit the progression of inflammation,and alleviate adverse reactions,which has high clinical application value.

Objective:To explore the research hotspots and effective promotion paths of post market surveillance and supervise of medical consumables with non-active medical devices.Methods:Data mining methods were used to collect related journal literatures and documents from the websites of China regulatory institutions and the China National Knowledge Infrastructure(CNKI),order sub item data of medical device adverse event reports,extract the MeSH element words of literatures and documents,perform bibliometric analysis and visual display.Results:The number of medical devices adverse event reports in China has been increasing year by year,reaching 694 866 in 2022,in the four statistical years from 2019 to 2022,the number of reports on non-active medical devices and IVD reagents also showed a parallel increasing trend,accounting for about 65.00% of the total number of adverse event reports on medical devices in the year.The bibliometric analysis of journal literature shows that research in this field has received varying degrees of participation from regulatory institutions,universities,medical institutions,and enterprises.Regulatory institutions have contributed 46 articles,accounting for 56.79% of the total number of articles,followed by 28 articles from universities.The co-occurrence analysis shows that hot topic is focused in 5 clusters:quality management,risk management,international experiences discussion and adverse event surveillance and re-evaluation and real-world research.China regulatory institutions attach great importance to post market surveillance and supervise,and have issued more than 20 relevant documents since 2006,focusing on specific topics and gradually deepening around safety and effectiveness.Conclusion:The post market surveillance and supervise of medical devices,especially medical consumables based on non-active medical devices,need to be promoted synchronously in three dimensions:regulatory institutions,medical institutions,and enterprises.Universities,research institutes,and industry organizations should work in coordinating to strengthen the collection,identification,and active surveillance of risk signals based on adverse event surveillance,safety evaluation based on risk management,and conducting real-world research,research and develop risk control and corrective and preventive measures.

In recent years， with frequent outbreaks of infectious diseases around the world， the global public health is faced with many threats and challenges. An infectious diseases early warning system is an important means for prevention and control of infectious diseases. As an important part of the early warning system， the warning indicators is crucial for understanding the occurrence and development trend of infectious diseases， detecting abnormal situations timely and effectively， and issuing early warning and initiating emergency response. Based on the occurrence and development process of infectious diseases， this paper summarizes the research status of early warning indicators on infectious diseases， in order to provide reference for the development and improvement of the infectious diseases early warning system.