Objective To study the protein expression levels of matrix metalloproteinases (MMPs)and their inhibitors in bone tissues of rat femoral head and to explore the relationship between necrosis of femoral head and glucocorticoid.Methods Twenty healthy adult SD rats were randomly divided into glucocorticoid group and control group,with 10 rats in each.Glucocorticoid group was treated with intramuscular injection of hydrocortisone twice a week.The control group received normal saline of the same volume.Four weeks later,bone tissues of left femoral head were collected from each group of rats for HE determination of femoral head necrosis.The expressions of matrix metalloproteinase-1 (MMP-1 ), matrix metalloproteinase-2 (MMP-2 ), tissue inhibitor of matrix metalloproteinase-1 (TIMP-1 ),and tissue inhibitor of matrix metalloproteinase-2 (TIMP-2 )at mRNA and protein levels were detected by RT-PCR and Western blot techniques,respectively.Results The expressions of MMP-1 and MMP-2 at mRNA and protein levels were higher in glucocorticoid group than those in the control group. However,TIMP-1 and TIMP-2 gene and protein expression levels were lower in glucocorticoid group (all P<0.05). Conclusion The expressions of MMPs in bone tissues of rat femoral head in early necrosis were increased,but their inhibitors had decreased expressions. We can draw the conclusion that glucocorticoid-induced necrosis of femoral head may be related to its regulation of the expression levels of MMPs and their related inhibitors.

Objective To investigate the risk factors of premature atherosclerotic three-vessel coronary artery dis?ease (CHD), and the association between single nucleotide polymorphism (SNP) of CD36 rs3211956, rs7755 and premature CHD. Methods Patient with premature three-vessel coronary artery disease (n=102) which were confirmed by consecutive coronary angiogram (lesion group) and patients (n=72) without CHD (control group) were enrolled in the study. Conventional CHD risk factors were compared between the two groups as well as SNPs of CD36 rs3211956 and rs7755 to disclose inde?pendent risk factor for CHD, which were measured by mass spectrometry. Results Among the conventional CHD risk fac?tors, male, HBP, high LDL-C, low HDL-C were independent risk factors of premature CHD. The GT genotype proportion of rs3211956 was significantly lower (χ2=8.042,P=0.005) in the lesion group than that in control group while the TT genotype proportion is significantly higher in lesion group compared with that in control group (χ2=6.191,P=0.014). Patients with the TT genotype have higher score of BMI than patients with GG or GT genotype (P=0.037). The G allele proportion of rs7755 in the lesion group was significantly higher than control group (χ2=3.636, P=0.047). Patients of the GG genotype have higher scores of BMI but lower level of HDL-C than those with AA or AG genotype (P<0.001). Logistic regression analysis re?vealed that after excluding a number of confounding factors, GG and TT genotype of rs3211956 and GG and GA genotype of rs7755 were respectively one of the independent risk factors for premature CHD. Conclusion The SNPs of CD36 rs7755 and rs3211956 may be the independent risk factors of premature coronary heart disease and might affect the the onset of CHD by affectting BMI and HDL-C.

Objective To analyze the clinical characteristics of children with knee joint diseases and discuss the curative effect of arthroscopy.Methods Eighty-nine children with knee joint diseases in Department of Orthopedics,the First Affiliated Hospital of Xinxiang Medical University from October 2012 to October 2015 were selected,and they were given knee arthroscopic surgery according to the disease types and characteristics,such as meniscal suture,suture plus angioplasty and synovectomy etc.All the symptoms,signs and the joint functions were recorded preoperatively and postoperatively.At the end of follow-up,surgical results were analyzed according to Lysholm score and International Knee Documentation Committee Knee evaluation form (IKDC) classification standard.Results The patients with discoid meniscus tear were the most,accounting for 55.55％ (55/99 knees).All patients were followed up for 6-30 months(the average time was 21 months) to find that all symptoms were relieved or disappeared within 1 year after operation.The outcome was evaluated according to the Tegner knee function:76 knees (76.76％) were markedly effective,16 knees (16.16％) were effective,6 knees (6.06％) were invalid and 1 knee (1.01％) was poor,and the excellent rate was 92.92％.The curative effect was evaluated according to Lysholm knee function score and IKDC score at the last follow-up.The Lysholm score in preoperation [(52.46 ± 4.79) scores] improved to (96.52 ± 3.97) scores in postoperation,and the difference was significant (t =-36.24,P ＜ 0.05);the IKDC score in preoperation [(46.52 ± 10.25) scores] improved to (90.67-± 5.89) scores in postoperation,and the difference was significant (t =-50.69,P ＜ 0.05).There was no joint infection,blood vessel or nerve damage and so on.Conclusions Meniscus tear is common in children with knee joint diseases,and most common is discoid lateral meniscus tear,and arthroscopy can have satisfactory outcome,with no obvious complications.Therefore,arthroscopic surgery is an ideal method for surgical treatment of children with knee joint disease.

Aim To study the apoptosis effect of Sir-aitia grosvenorii extract on human lung cancer cells A549 and its mechanisms.Methods MTT assay was applied to determine A549 cell proliferation.Hoechst 33258 staining was applied to investigate morphological changes in A549 cells.To find out the cause of cell growth inhibition,several experiments on cell cycle distribution and apoptosis were performed by flow cy-tometry analysis.The expression of p21 and Bcl-2 was determined by Western blot.Results Flow cytometry analysis showed that treatment with mogrol arrested A549 cells in the G0 /G1 phase and induced apoptosis. After treatment with Siraitia grosvenorii extract,West-ern blot experiment showed cell cycle regulator p21 was up-regulaed,while the apoptosis inhibitor Bcl-2 was down-regulated.Conclusion Treatment with Siraitia grosvenorii extract arrests the A549 cells at G0 /G1 phase and induces apoptosis that may contribute to the anti-proliferation activity of mogrol through the regula-tion of p21 and Bcl-2 expression.

Objective:To investigate the expression of Galectin-7 in the bronchial mucosa of asthmatic children and its effect on the apoptosis of bronchial epithelial cells.Methods:Bronchial mucosa of asthmatic children and children with bronchial dilation were collected and the expression of Galectin-7 was detected by Western blot.Human bronchial epithelial cells were cultured in vitro,the cells were transfected with Galectin-7 siRNA to interfere the Galectin-7 expression,while siRNA control was transfected as the control group.The experiment was divided into normal group,control group,infected group and experimental group.The normal group was normal human bronchial epithelial cells,the cells in the control group was transfected with siRNA control,the infected group was infected with RSV,the experimental group was transfected with Galectin-7 siRNA and infected with RSV.After 24h culture,Galectin-7 protein expression and cell apoptosis were detected in the cells of each group.Western blot was used to detected the expression of Bcl-2,Bax,STAT3 and p-STAT3.Results:The expression of Galectin-7 in bronchial mucosa of asthmatic children was significantly higher than that of the non asthmatic children (P＜0.01).There was no significant difference in the Galectin-7 level between the normal group and the control group (P＞0.05).The levels of Galectin-7,Bax and apoptosis in the infected group were significantly higher than those in the normal group,while the levels ofp-STAT3 and Bcl-2 were significantly lower than those in the normal group (P＜0.01).The levels of Galectin-7,Bax and apoptosis in the experimental group were significantly lower than those in the infected group,while the levels of p-STAT3 and Bcl-2 were significantly higher than those in the infected group (P＜0.01).Conelusions:The expression of Galectin-7 was up-regulated in the bronchial mucosa of asthmatic children,which might promote the apoptosis of bronchial epithelial cells by activating STAT3.

OBJECTIVE： To study the effects of berberine hydrochloride on the pharmacokinetics of tacrolimus in rats after single or multiple administration， and to provide reference for clinical combination therapy. METHODS： 30 rats were randomly divided into 5 groups， with 6 rats in each group： group one was treated with single administration of tacrolimus； group two was treated with tacrolimus intragastrically， twice a day， for consecutive 1 week； group three was treated with single administration of berberine hydrochloride， 5 min later given single administration of tacrolimus； group four was treated with tacrolimus intragastrically， twice a day， for consecutive 1 week， and then given tacrolimus intragastrically once 5 min after intragastric administration of berberine hydrochloride on the 8th day； group five was treated with berberine hydrochloride intragastrically， twice a day， and given tacrolimus intragastrically every 5 min， for consecutive 8 d. The doses of berberine hydrochloride and tacrolimus were 200 mg/kg and 0.945 mg/kg. The blood samples 0.3 mL were collected from posterior orbital venous plexus of rats 0， 5， 15， 30 min and 1， 2， 3， 4， 6， 8， 12 h after last intragastric administration of tacrolimus. The concentration of tacrolimus in rat whole blood was determined by LC-MS/MS. DAS 2.0 software was used for pharmacokinetic study. RESULTS： Compared with group one， the pharmacokinetic parameters AUC0-12 h， AUC0-∞ and MRT0-12 h of tacrolimus in rats were decreased significantly in group three （P＜0.05），while there was no statistical significance in all pharmacokinetic parameters of tacrolimus in group four （P＞0.05）. Compared with group two， AUC0-12 h of tacrolimus was decreased significantly while CLz was increased significantly in group four （P＜0.05）； there was no statistical significance in all pharmacokinetic parameters of tacrolimus in group five （P＞0.05）. CONCLUSIONS： Single and multiple intragastric administration of berberine hydrochloride has a certain effect on the pharmacokinetics of tacrolimus in rats， it shows that there is a downward trend in blood drug concentration and needs to be used with caution.

OBJECTIVE：To study the research status ，hotspots and frontier cha nges of drug-induced kidney injury （DIKI）， and to provide reference for the research of DIKI in China. METHODS ：Literatures related to DIKI published from 2001 to 2020 were retrieved from Web of Science database. CiteSpace 5.7.R2 software was used to conduct visualization analysis for DIKI related literatures from aspects of the number of publications ，authors and cited authors ，institutions，countries，related disciplines ， co-cited journals ，co-cited literatures and keywords. RESULTS ：A total of 1 320 literatures were included ，and the number of published literatures about DIKI researches showed an upward trend during 2001-2020. The most studies and the highest co-citations were devoted by the Yale University scholar Mark A Perazella （18 literatures，cited for 137 times）. There were 76 countries carrying out research in this field ，among which the United States had the first advantage （445 literatures，accounting for 34.29％ of the total number of literatures ）. A total of 2 175 institutions participated in this field ，of which Yale University contributed the most publications ；pharmacology，nephrology，toxicology and other related disciplines were involved in this field ；Kidney International（652 literatures，USA）published the most research in this field ；the most frequently cited literature was “Drug- induced nephrotoxicity ：clinical impact and preclinical in vitro models ”，published by Tiong et al in 2014. Through the keyword cluster analysis ，the research hotspots in this field mainly focused on the risk factors of DIKI ，the research of DIKI in special groups，the mechanism of DIKI related drugs ，the exploration of DIKI biomarkers ，and the preclinical research of DIKI. CONCLUSIONS：DIKI’s research has been paid more and more attention by scholars ，but the cooperation between China and other countries in this field is limited. In the future ，more attention should be paid to the research hotspot in this field and international exchanges and cooperation should be strengthened.

OBJECTIVE To analyze the si tuation and hot spots of gabapentinoid drugs in the treatment of pain. METHODS Related researches about gabapentinoid drugs in the treatment of pain were retrieved from Web of Science core collection database during Jan. 1st，2011-Dec. 31st，2020. VOSviewer 1.6.17，CiteSpace 5.8.R1 and Excel 2018 software were used to statistically analyze the key characteristics of relevant literature ，such as the annual publications ，countries/regions，institutions，authors， journals and research hot spots. RESULTS & CONCLUSIONS A total of 3 519 literatures were retrieved ，and the annual publication outputs showed an upward trend generally. Totally 86 countries/regions had conducted relevant studies ，of which the United States ranked first （up to 1 219），and had close cooperation with the United Kingdom ，Canada，China，Germany，Japan， etc；a total of 3 996 institutions had published relevant literatures ，and the Pfizer Inc. issued the most publications ；the most studies were devoted by Professor Parsons from the University of California San Diego ，and the highest co-citations author was Professor Gilron from the Queen ’s University. Among 1 185 journals，Pain ranked first not only in the high-productive journal ，but also in the co-cited journal. The main hot topics include abuse and misuse of gabapentinoid ，off-label use of gabapentinoid ，clinical application of gabapentinoid as a component of multimodal analgesia ，and the update of guidelines for pain based on systematic evaluation and meta-analysis.

OBJECTIVE To investigate the clinical efficacy and safety of rituximab （RTX） followed by belimumab （BLM） in patients with severe systemic lupus erythematosus（SSLE）. METHODS Nine SSLE patients， who were treated with RTX followed by BLM for more than 6 months in the Department of Rheumatology and Immunology of the First Affiliated Hospital of Zhengzhou University from October 2020 to June 2021， were enrolled. Baseline clinical data of patients， laboratory examination results and basic treatment status at weeks 0， 4， 12， and 24 of medication were collected retrospectively. The patients’ systemic lupus erythematosus disease activity index （SLEDAI） score， glucocorticoid dosage and serological indicators （complement C3， complement C4， serum albumin， and 24-hour urine protein quantification） level were analyzed. At the same time， the occurrence of adverse drug reaction was collected. RESULTS All 9 patients completed more than 24 weeks of RTX followed by BLM therapy. All patients suffered from renal impairment， of which 7 （77.8%） had renal pathology support， 3（33.3%） had blood system damage and 2 （22.2%） had nervous system damage. During treatment， with the prolongation of treatment time， the SLEDAI score， 24- hour urinary protein quantification， and glucocorticoid dosage of patients showed a significant downward trend， and ultimately decreased to the normal index level （P＜0.05）； serum albumin， complement C3 and complement C4 all showed a significant upward trend， eventually rose to the normal index level （P＜0.05）. During treatment and follow-up， 1 patient developed herpes zoster， 1 patient developed upper respiratory tract virus infection， and 1 patient developed urinary system bacterial infection. All patients recovered after symptomatic treatment. CONCLUSIONS In sequential use of RTX followed by BLM for SSLE， early administration of RTX can quickly stabilizethe condition， significantly alleviate clinical symptoms， and gradually normalize specific serological indicators； subsequent administration of BLM can reduce the type and dosage of basic treatment drugs； there is no increase in the incidence of adverse drug reactions.