Objective:To evaluate the relationship between Sestrin2 and mitochondrial DNA (mtDNA)-NOD-like receptor associated protein 3 (NLRP3) inflammasome pathway during endotoxin-induced myocardial injury in mice.Methods:One hundred and eighty-four clean-grade healthy male ICR mice, aged 8-12 weeks, weighing 20-25 g, were used in this study. One hundred and sixty-eight mice were divided into 7 groups ( n=24 each) using the random number table method: normal control group (N group), lipopolysaccaride(LPS) group (L group), mtDNA group, LPS+ mtDNA group (M group), normal control+ negative control adeno-associated virus (AAV-NC)group (NC group), LPS+ mtDNA+ AAV-NC group (MC group), and LPS+ mtDNA+ Sestrin2 overexpression adeno-associated virus (AAV-Sestrin2) group (MSgroup). Another 10 mice were used to detect the transfection effect of AAV-Sestrin2, and the left 6 mice were used for mtDNA extraction. The model of endotoxemia was developed by intraperitoneal injection of LPS 10 mg/kg. mtDNA 5 mg/kg was intraperitoneally injected in mtDNA group, and mtDNA 5 mg/kg was intraperitoneally injected at 30 min after LPS injection in M group.AAV-Sestrin2 150 μl was injected via the tail vein in MS group, and the equal volume of AAV-NC was injected via the tail vein in MC and NC groups. Four weeks after virus injection, LPS 10 mg/kg was intraperitoneally injected and 30 min later mtDNA 5 mg/kg was intraperitoneally injected in MS and MC groups. Blood samples were collected at 24 h after LPS injection for determination of serum creatine kinase-MB (CK-MB) and lactate dehydrogenase (LDH) activities (by biochemical assay), concentrations of serum cardiac troponin I (cTnI), interleukin-18 (IL-18) and interleukin-1beta (IL-1β)(by enzyme-linked immunesorbent assay), and expression of mtDNA (by quantitative real-time polymerase chain reaction). The animals were sacrificed after the end of blood sampling and myocardial tissues were obtained for determination of the contents of reactive oxygen species (ROS), total antioxidant capacity (T-AOC), and adenosine triphosphate (ATP) and expression of NOD-like receptor associated protein 3 (NLRP3), active subunit p20 of caspase-1 (caspase-1p20) and apoptosis-associated microprotein (ASC) in myocardial tissues (by Western blot) and for microscopic examination of the pathological changes after HE staining (with a light microscope). Results:Compared with N group, the levels of CK-MB, LDH, cTnI, IL-1β and IL-18 in serum were significantly increased, the expression of mtDNA was up-regulated, the ROS content in myocardial tissues was increased, the T-AOC and ATP contents in myocardial tissues were decreased, the expression of NLRP3, caspase-1p20 and ASC in the myocardial tissues was up-regulated( P<0.05), and the pathological changes of myocardial tissues were aggravated in L group and mtDNA group.Compared with L group and mtDNA group, the levels of CK-MB, LDH, cTnI, IL-1β and IL-18 in serum were significantly increased, the expression of mtDNA was up-regulated, the ROS content in myocardial tissues was increased, the T-AOC and ATP contents in myocardial tissues were decreased, the expression of NLRP3, caspase-1p20 and ASC in the myocardial tissues was up-regulated( P<0.05), and the pathological changes of myocardial tissues were aggravated in M group. Compared with M group, the levels of CK-MB, LDH, cTnI, IL-1β and IL-18 in serum were significantly decreased, the expression of mtDNA was down-regulated, the ROS content in myocardial tissues was decreased, the T-AOC and ATP contents in myocardial tissues were increased, the expression of NLRP3, caspase-1p20 and ASC in the myocardial tissues was down-regulated( P<0.05), and the pathological changes of myocardial tissues were significantly attenuated in MS group. Conclusions:Sestrin2 can reduce endotoxin-induced myocardial injury in mice by alleviating mitochondrial damage, inhibiting oxidative stress, protecting mtDNA from oxidative damage, and then inhibiting mtDNA-NLRP3 inflammasome pathway.

OBJECTIVE To evaluate the efficacy， safety and cost-effectiveness of polyisobutylene （PIB）-type Gutong plaster （called “PIB Gutong plaster” for short） versus non-steroidal anti-inflammatory drugs （NSAIDs） in the treatment of osteoarthritis in Chinese adults. METHODS Based on a real-world study， after propensity score matching， the decrease in pain visual simulation score， utility increase， time to pain resolution， time to return to normal range of motion and total adverse events of PIB Gutong plaster versus three NSAIDs （celecoxib， diclofenac sodium， and ibuprofen） were evaluated. Cost-utility analysis was used to calculate the incremental cost-effectiveness ratio （ICER） of patients using PIB Gutong plaster versus the three NSAIDs from the perspective of the whole society， and sensitivity analysis was carried out. RESULTS In terms of effectiveness， the recovery time of joint activity in PIB Gutong plaster group was significantly longer than that in celecoxib group， the decrease in VAS score of PIB Gutong plaster was significantly higher than that of ibuprofen but significantly lower than that of diclofenac sodium； the time of pain disappearance was longer than that in diclofenac sodium group and ibuprofen group， and the increase in health utility was significantly lower than that in diclofenac sodium group （P＜0.05）. In terms of safety， there were no significant differences in the incidence and severity of adverse events of PIB Gutong plaster， compared with the three NSAIDs， without statistical significance （P＜0.05）. In terms of cost-effectiveness， compared with celecoxib and diclofenac sodium， PIB Gutong plaster was dominant. Compared with ibuprofen， the ICER value of PIB Gutong plaster was 178 611.58 yuan/QALY， indicating that at the current price， PIB Gutong plaster was cost-effective if the threshold was 3 times GDP per capita. The results of sensitivity analysis were consistent with those of basic analysis. CONCLUSIONS The efficacy of PIB Gutong plaster was better than that of ibuprofen， similar to that of celecoxib， but worse than that of diclofenac sodium， the safety was consistent with the three NSAIDs， and the cost-effectiveness of PIB Gutong plaster needs to be improved.

ObjectiveTo investigate the protective effect of cytochrome P4502D6 （CYP2D6） and cytochrome P4503A4 （CYP3A4）， key enzymes of drug metabolism in liver， on acute liver injury in water extract of Glycyrrhizae Radix et Rhizoma （WEOGRR）. MethodHealthy male Kunming mice were divided into normal group， model group， WEOGRR low-， medium- and high-dose groups （5， 10， 15 g·kg^-1·d^-1） and positive drug group （diammonium glycyrrhizinate， 75 mg·kg^-1·d^-1）， with 10 in each group. One week after preventive administration， acute liver injury model was induced by single intragastric administration of 270 mg·kg^-1 Tripterygium Glycosides tablets， and samples were collected after 18 h. The pathological changes of liver were observed by hematoxylin-eosin （HE） staining. Serum liver function indexes including alanine aminotransferase （ALT）， aspartate aminotransferase （AST）， γ-glutamyl transpeptadase （γ-GT）， alkaline phosphatase （ALP）， and total bilirubin （TBIL） as well as the levels of oxidative stress indexes including malondialdehyde （MDA） and superoxide dismutase （SOD） in hepatocytes were determined by biochemical method. Real-time polymerase chain reaction （Real-time PCR） and Western blot were performed to detect the mRNA and protein expression levels of CYP2D6 and CYP3A4， respectively. ResultCompared with normal group， model group had significant hepatocyte swelling and inflammatory cell infiltration （P<0.01）， increased AST， ALT， γ-GT， ALP and TBIL （P<0.05）， elevated MDA and decreased SOD （P<0.01） as well as down-regulated mRNA and protein expression levels of CYP2D6 and CYP3A4 （P<0.05）. Compared with the model group， the normal group had intact liver structure without obvious abnormality， and the WEOGRR groups and positive drug group presented alleviated hepatocyte swelling and inflammatory cell infiltration （P<0.01）， reduced AST， ALT， γ-GT， ALP and TBIL （P<0.01）， lowered MDA and increased SOD （P<0.01） as well as up-regulated expression levels of CYP2D6 and CYP3A4 （P<0.01）. ConclusionThe protective effect of WEOGRR on acute liver injury induced by Tripterygium glycosides tablets may be related to reducing the contents of AST， ALT， γ-GT， ALP and TBIL in serum， inhibiting MDA and increasing the activity of SOD in liver cells， and enhancing the activities of CYP2D6 and CYP3A4， thus accelerating the metabolism of toxic substances.

Objective:To analyze the current situation and requirements of education for health technicians in maternal and child health care institutions, and put forward feasible strategies and measures to improve the comprehensive quality and professional level of the talent team of maternal and child health care institutions.Methods:Questionnaire survey was carried out on education needs of health technical staff of 11 maternal and child health care hospitals in 4 provinces (regions), and provincial, municipal and district-level medical institutions. The survey results were recorded by Epidata 3.1. SPSS 22.0 software was used for statistical analysis.Results:A total of 1 678 questionnaires were included in the analysis. A total of 1 313 people received training, accounting for 78.2%. The main reason for not receiving training was that the unit didn't arrange (180 people), accounting for 49.3%(180/365). There were 779 people who had more than 3 days of training, accounting for 59.3%. There were 384 people who were trained in superior general hospitals, accounting for 29.2%, and 268 people were trained in superior maternal and child health institutions, accounting for 20.4%. There were 837 people who learned the content of new professional progress, accounting for 50.8%(837/1 648). According to the interview, there were still some requirements for thematic training, further education, online learning, continuing education and standardized training.Conclusion:Maternal and child health care institutions have accelerated the construction of professional personnel, intensified training, and thoroughly implemented health personnel training programs, established a long-term mechanism, increased funding, improved training content, ensured the quality of training, and made a good job in hierarchical training to meet the learning needs of personnel at all levels. This is of great significance for strengthening the technical personnel of maternal and child health care institutions and improving their service capacity.

OBJECTIVE：To review the method and results of pharmacoeconomic evaluation of aspirin for cardiovascular disease prevention ，and to provide reference for economic evaluation of aspirin and clinical medication decision. METHODS ： Using“cardiovascular disease ”“cost-effectiveness”“cost-utility”“cost-benefit”“cost effectiveness ”“cost utility ”as the Chinese search terms ，using“cost-effectiveness”“cost-utility”“cost-benefit”“economic analysis ”“pharmacoeconomics”as English search terms，relevant literatures about pharmacoeconomic evaluation of aspirin for cardiovascular disease prevention published during January 1，2000 to January 17，2021 were retrieved from CNKI ，Wanfang database ，VIP，PubMed，Web of Science ，the Cochrane Library. After screening literatures according to inclusion and exclusion criteria ，extracting relevant data ，the quality of included literatures was evaluated with CHEERS scale. The method and results of pharmacoeconomic evaluation of aspirin in the prevention of cardiovascular diseases were analyzed statistically in terms of basic information ，literature quality ，model structure and elements ，health status and utility value ，cost items and sources ，health output ，economic evaluation and sensitivity analysis. RESULTS & CONCLUSIONS ：Nine literatures were included ，and the total coincidence rates of the literatures were all above 80.00％. The pharmacoeconomic evaluation of aspirin in the prevention of cardiovascular disease mainly adopted Markov model ， and the model structure was relatively mature. The cost mainly considered the direct cost ，and the data mainly came from the medical insurance database ；utility was calculated according to the utility value of health state ，which mostly came from the existing literatures. The sensitivity analysis adopted deterministic sensitivity analysis and probabilistic sensitivity analysis ，and the main influential factor was cost. It was economical to use aspirin for cardiovascular disease prevention in most cases ，and aspirin was more economical for primary prevention of cardiovascular disease. It is suggested that domestic scholars can refer to China ’s pharmacoeconomic guidelines to carry out relvant pharmacoeconomic evaluation research more standardized.

Objective:To evaluate the effect of dexmedetomidine on pyroptosis in mice with acute renal injury induced by endotoxin and the relationship with miRNA-223-3p.Methods:Thirty-two clean-grade healthy male ICR mice, aged 8-12 weeks, weighing 20-25 g, were divided into 4 groups ( n=8 each) using the random number table method: control group (group C), lipopolysaccharide (LPS) group (group L), LPS plus dexmedetomidine group (group LD), and LPS plus dexmedetomidine plus atipamezole group (group LDT). The model of acute renal injury induced by endotoxin was established by intraperitoneal injection of LPS 400 μg/kg, followed by intraperitoneal injection of LPS 10 mg/kg 8 h later.Dexmedetomidine 40 μg/kg was intraperitoneally injected once every 2 h for 3 times in total starting from 30 min after establishing the model in group LD.Atipamezole 750 μg/kg was intraperitoneally injected immediately after establishing the model, and 30 min later dexmedetomidine 40 μg/kg was intraperitoneally injected once every 2 h for 3 times in total in group LDT.The equal volume of normal saline was intraperitoneally injected in group C. Blood samples were collected from the heart at 24 h after establishing the model, and serum creatinine (Cr) and blood urea nitrogen (BUN) concentrations were measured with an automatic biochemical analyzer.The animals were sacrificed and the left kidney tissues were obtained for microscopic examination of pathological changes after HE staining (with a light microscope) and for determination of the expression of caspase-1 p20, NOD-like receptor thermoprotein structural domain-related protein 3 (NLRP3) and ASC protein and mRNA (by quantitative real-time polymerase chain reaction and Western blot), contents of interleukin-1beta (IL-1β) and IL-18 (by enzyme-linked immunosorbent assay), and rate of pyroptosis in renal cortical cells (by TUNEL). Results:Compared with group C, the concentrations of serum Cr and BUN were significantly increased, the expression of NLRP3, caspase-1 p20 and ASC protein and mRNA in the renal tissues was up-regulated, the contents of IL-1β and IL-18 were increased, the rate of pyroptosis in renal cortical cells was increased ( P<0.05), no significant change was found in the expression of miRNA-223-3p ( P>0.05), and pathological changes of kidney were accentuated in group L. Compared with group L, the concentrations of serum Cr and BUN were significantly decreased, the expression of NLRP3, caspase-1 p20 and ASC protein and mRNA in the renal tissues was down-regulated, the contents of IL-1β and IL-18 were decreased, the rate of pyroptosis in renal cortical cells was decreased, the expression of miRNA-223-3p was up-regulated ( P<0.05), and pathological changes of kidney were attenuated in group LD.Compared with group LD, the concentrations of serum Cr and BUN were significantly increased, the contents of IL-1β and IL-18 were increased, the expression of NLRP3, caspase-1 p20 and ASC protein and mRNA in the renal tissues was up-regulated, the rate of pyroptosis in renal cortical cells was increased, the expression of miRNA-223-3p was down-regulated ( P<0.05), and the pathological changes of kidney were accentuated in group LDT. Conclusion:The mechanism by which dexmedetomidine reduces acute renal injury may be related to up-regulating the expression of miRNA-223-3p and inhibiting pyroptosis in mice.

Objective:To explore the curative effect of surgical treatment for Crohn′s disease (CD), to investigate the timing of surgical intervention and the choice of surgical methods.Methods:From January 1, 2016 to August 31, 2020, at Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, the clinical data of 123 patients with CD and receiving surgical treatment were retrospectively analyzed, which included the type of lesion, the location of lesion, clinical manifestation, surgical method, preoperative inflammatory and nutritional indicators, postoperative recovery of digestive tract function, and the development and treatment of postoperative complications. CD was diagnosed according to Consensus opinion on diagnosis and treatment of inflammatory bowel disease ( Beijing 2018). Patient was classitied according to the Montreal Classification. Postoperative complications were graded according to the Clavien-Dindo Criteria. Mann-Whitney U test was used for statistical analysis. Results:Among 123 patients, according to the Montreal classification, two cases (1.6%) were diagnosed at ≤16 years old (type A1), 66 cases (53.7%) were diagnosed at 17 to 40 years old (type A2), and 55 cases (44.7%) were diagnosed at >40 years old (type A3). The lesions were 52 cases (42.3%) of terminal ileum (L1) type, 20 cases (16.3%) of colon (L2) type, and 51 cases (41.5%) of ileocolon (L3) type. Four cases (3.2%) were non-stenosis and non-penetrating (B1) type, 87 cases (70.7%) were stenosis (B2) type, and 32 cases (26.0%) were penetrating (B3) type. Eighteen patients (14.6%) underwent emergency surgery due to complete intestinal obstruction (10 cases), gastrointestinal perforation (five cases), gastrointestinal bleeding (two cases), and rectovesical fistula complicated with septic shock (one case). One hundred and five patients (85.4%) received selective surgery due to poor conservative treatment effects. 51 cases (41.5%) underwent traditional open surgery and 72 cases (58.5%) underwent laparoscopic surgery. Nineteen patients (15.4%) received temporary or permanent ostomy. The preoperative C reactive protein level of patients with emergency surgery was higher than that of patients undergoing selective surgery ((39.23±24.13) mg/L vs. (11.48±2.68) mg/L), while the levels of plasma albumin (ALB) and pre-ALB were lower than those of patients receiving selective surgery ((29.90±10.60) g/L vs. (38.38±8.30) g/L, (146.00±125.49) mg/L vs. (209.06±61.19) mg/L), and the differences were statistically significant ( Z=9.603, 8.754 and 7.111, all P<0.01). During the follow-up, a total of 23 cases (18.7%) developed postoperative complications, including one case of postoperative intra-abdominal hemorrhage and underwent re-operation (Clavien-Dindo grade Ⅲ complication); four cases of anastomotic leakage after operation; six cases of postoperative paralytic ileus; 11 cases of surgical site infection, all of which were Clavien-Dindo grade Ⅱ complications, and one case of deep venous thrombosis of lower extremity. No patient with severe intraoperative complication was observed, and no patients died during the operation or hospitalization. The postoperative exhaust time of patients was (3.2±1.4) d, the time of open fluid diet was (5.8±0.8) d, the length of hospital stay was (18.0±14.1) d, and the length of postoperative hospital stay was (11.2±8.8) d. Conclusions:The concept of multidisciplinary collaboration should be emphasized in the treatment of CD. Surgical treatment can effectively control the complications and improve the quality of life of patients, but the timing of operation and the choice of surgical methods should be decided prudently after perioperative treatment, multi-disciplinary participated and regulation of the internal environment. The standardized and targeted treatments for the surgical difficulties of inflammatory bowel disease should be conducted.

Objective:To compare the osteogenesis ability between human umbilical cord Wharton's Jelly-derived mesenchymal stem cells(hUCWJMSCs) and human periodontal ligament mesenchymal stem cells (hPDLSCs) in vitro.Methods:hUCWJMSCs and hPDLSCs were in vitro cultured.The cell proliferation capacity was examined by MTT assay.After osteogenesis induction culture,ALP activity of the cells was determined,minerialization was observed by alizarin red staining,OPN and Runx2 mRNA expression was analyzed by Real-time PCR.Results:hUCWJMSCs grew faster than hPDLSCs.After osteogenic differentiation induction,hPDLSCs group showed higher ALP level,more mineralized nodule formation and higher Runx2 expression compared with hUCWJMSCs group (P ＜ 0.05);while the OPN expressed higher in hUCWJMSCs than in hPDLSCs (P ＜ 0.05).Conclusion:hUCWJMSCs and hPDLSCs have osteogenesis differentiation potential,hPDLSCs are more osteogenetic.

Objective To analyze the efficacy and tolerance of methotrexate(MTX)in remission maintenance of Crohn′s disease (CD).Methods From June 2012 to August 2015 ,49 CD patients who received MTX as mainly treatment medication to maintain remission were enrolled.The pre-medication history,efficacy,dosage and side effects of MTX were analyzed.The effects of inducing strategy on disease recurrence were analyzed.Chi-square test and t test were used for statistical analysis.Results Among the 49 patients,34 (69.4%)received steroids for remission inducing,nine (18.4%)received infliximab for remission inducing and six (12.2%)achieved remission after operation.In the 44 patients treated with azathioprine (AZA)before,the median treatment time was one month and the dosage for withdrawal of AZA was (42.0 ± 14.8)mg/d.The most common reason was leucopenia (81 .8%, 36/44).Till the time point of follow-up,46 of the 49 CD patients still took MTX orally with a median treatment time of 16 months,and the weekly dosage was (12.7 ±2.0)mg.Thirty-one cases (67.4%) achieved clinical stability,while 15 cases (32.6%)underwent clinical recurrence.The median Crohn′s disease activity index (CDAI)was 123.5 ± 66.6.The weekly dosage of clinical stability group was (12.5 ±2.1)mg,and that of clinical recurrence group was (13.0 ±1 .7 )mg,there was no statistically significant difference between the two groups (t =0.802,P =0.426 ).The recurrence rate of steroids-induced remission group was 41 .2% (14/34 ),which was higher than that of infliximab and surgery-induced remission group (1/15),and the differnce was statistically significant (χ2 =5 .177,P =0.023 ). The common side effects were gastrointestinal reaction (26.5 %, 13/49 ), impaired liver function (20.4%,10/49)and leukopenia (12.2%,6/49).Only three cases could not tolerate the side effects and underwent medication withdrawal.Conclusions As a second-line immunosuppressant for maintanence remission in CD,MTX is effective and well-tolerated in patients.So it can be an important option during the long course of CD.

Objective To investigate the expression levels of MiR‐96 ,HIF‐1α,Twist and Slug and other predisposing gene in cervical cancer .Methods In this study ,128 patients with cervical cancer treated in our hospital from March 2010 to May 2014 were selected as the observation group ,and 100 cases of healthy people were selected as control group .MiR‐96 ,HIF‐1α,Twist and Slug and other predisposing gene expression levels in cancer tissues were tested .(1) HIF‐1α:HIF‐1α kit was used to detect HIF‐1αmonoclonal antibodies ,the kit was prepared and stained according to the requirements ,and the positive cell rate greater than 10%under the microscope were positive .(2) MiR‐96 ,Twist and Slug:total RNA was extracted according to the instructions ,the RNA was reverse transcribed ,the relative expression values MiR‐96 ,Twist and Slug were detected by quantitative PCR .Results (1) HIF‐1αwas not expressed in normal tissues .And in tumor tissues ,the positive expression rate was much higher than that of normal tissue ,there was a significant difference(P<0 .05);(2)the relative expression values of MiR‐96 in tumor tissue were much greater than that of normal tissue (P<0 .05);(3) the relative expression rate of Twist and Slug gene in the tumor tissue were also much higher than that of normal organizations (P<0 .05) .Conclusion Compared with normal tissues ,MiR‐96 ,HIF‐1α,Twist and Slug gene expression in tumor tissues are significantly greater .