Objective To evaluate the role of interlukin-6 and signal transducer and activator of transcription 3 (IL-6/STAT3) signaling pathway in the up-regulation of high mobility group box 1 (HMGB1) expression in lung tissues in septic rats.Methods Ninety healthy male Wistar rats,aged 10-14 weeks,weighing 250-300 g,were randomly divided into 3 groups (n =30 each):sham operation group (group S),cecal ligation and puncture (CLP) group and anti-IL-6 monoclonal antibody group (group IL-6).Sepsis was induced by CLP.Anti-IL-6 monoclonal antibody 0.5 mg/kg was injected intraperitoneally 1 h before CLP,while the equal volume of normal saline was given in groups S and CLP.Six rats in each group were sacrificed at 6,12,24,48 and 72 h after CLP and lungs were removed for determination of HMGB1 content (by RT-PCR),HMGB1 mRNA expression (by ELISA) and STAT3-DNA binding activity (by electrophoretic mobility shift assay) in lung tissues.Results Compared with S group,HMGB1 content,HMGB1 mRNA expression and STAT3-DNA binding activity were significantly increased in groups CLP and IL-6 (P ＜ 0.05).HMGB1 content,HMGB1 mRNA expression and STAT3-DNA binding activity were significantly lower in group IL-6 than in group CLP (P ＜ 0.05).Conclusion IL-6/STAT3 signaling pathway is involved in the up-regulation of HMGB1 expression in lung tissues in septic rats.

This paper presented the practice of Zhejiang in introducing the drug zero-profit reform.A comparative analysis was made to the pilot county hospitals regarding their business performance,patients' burden,financial subsidy and medical insurance expenditure.The reform has scored a success as expected with the following outcomes:sharp rise in medical services volume,medical income and financial aid on one hand; drop of the proportion of drug income and changes in the medical income makeup; controlled increase of average cost of outpatient and inpatient care,and significant drop of pharmaceutical costs; increased expenditure yet stable operation of medical insurance funds;proportional increase of medical insurance compensation,with drops of the proportion of both out-ofpocket expenses and visits to doctors out of their county.This reform,however,has such shortcomings as follows:insufficient adjustment toward true costs of medical services,lack of a clear and sustainable financial compensation mechanism,and that of supporting measures.Based on these,the authors call for accelerated payment system reform,dynamic and scientific adjustment of medical service prices,exploration of clear financial compensation methods,optimization of internal management of hospitals,and acceleration of the formation of a medical staff income distribution mechanism.

Aim To evaluate the efficacy of TFU as a precursor of 5-FU on the growth inhibition of human gastric carcinoma cell lines SGC-7901 and MKN-45.Methods In vitro experiments,cell growth inhibition was measured by MTT assay.The rates were compared in the presence and Absence of liver microsomal enzymes.The morphology of apoptotic cells was detected by observation with a fluorescence microscope after staining by using adridine orange/ethidium bromide solution.DNA fragmentation was analyzed by agarose gel electrophoresis and flow cytometry respectively.Western blot was employed to analyze the expression of Bcl-2 and Bax.The in vivo efficacy of TFU was assessed in nude mice bearing tumours.The specimens were re-moved and the in situ cell apoptosis detection kit was employed for TUNEL staining.Results Growth of SGC-7901 and MKN-45 cells was remarkably suppressed by treatment with TFU in the presence of liver microsomal enzymes in vitro,suggesting that TFU might be converted to 5-FU by the enzymes.Similar treatment of TFU induced apoptosis of the cells,which was deduced from typical apoptotic features such as morphology,the formation of characteristic ladder pattern of DNA migration and the accumulation of sub-G1 phase.Furthermore,a significant inhibition of Bcl-2 expression and the up-regulation of Bax were observed after treatment with TFU in the presence of liver microsomal enzymes.Growth of human gastric carcinoma cells was significantly delayed by oral administration of TFU with low side effects.Apoptosis in xenografts was also observed by means of TUNEL staining method.Conclusion Treatment of TFU in the presence of liver microsomal enzymes could promote the inhibition of gastric carcinoma cell proliferation.TFU might sustain release of 5-FU mediated by liver microsomal enzymes.Low dose of 5-FU might trigger the carcinoma cells apoptosis via regulation of Bax and Bcl-2.

Objective To investigate the level about illness perception in patients with coronary heart disease. Methods From July to De-cember, 2015, 198 inpatients with coronary heart disease who were admitted into hospitals twice or more were enrolled. They were assessed with Illness Perception Questionnaire-Revised (IPQ-R). Results The score of common symptoms was (4.55±1.64). The symptoms, for exam-ple, chest pains, uncomfortable feeling in chest, cold sweat, flustered and breathlessness were most frequently experienced and most often identified. For the illness perception part, the scores on subscales of treatment control and consequences were higher than 3, which was the neutral point. For the cause dimension part, the highest scores was (3.38 ± 0.90) in diet or eating habits, followed by (3.38 ± 0.89) in aging. Among these factors, immune factors had the highest mean score, followed by stress factor. Conclusion The level of illness perception in pa-tients with coronary heart disease was in the middle level, and individual differences were obvious. The awareness of the disease and the in-tervention of the patient should be strengthened.

Objective To observe the protective effects of lovastatin against lung injury and the expression changes of adiponectin in the septic rats.Methods Fifty four male Wistar rats weighting 250-300g were randomly divided into the three groups:sham operation group ( group Sham) ,sepsis group ( group CLP) and lovastatin interven tion group (group LOV).Rats were injected with lovastatin (4mg/kg) or 0.5%CMC (vehicle) for five days and then subjected to CLP.At 4h,12h and 24h after operation.BALF was collected to determine the levels of TNF-αand IL-6,lung tissue was obtained to observe histopathological changes,and to detect the content of MPO and MDA,the blood sample was obtained to detect the level of adiponectin.Results In the group Sham,at 4h,12h and 24h time points,the levels of TNF-αwere (1.80 ±0.13)pg/mL,(2.04 ±0.15)pg/mL and (1.930.19)pg/mL;the levels of IL-6 were (20.56 ±0.23)pg/mL,(18.35 ±0.15) pg/mL and (21.23 ±0.20) pg/mL;the contents of MPO were (2.82 ±0.14) U/g tissue,(2.88 ±0.07) U/g tissue and (2.76 ±0.18) U/g tissue;and the levels of MDA were (3.32 ±0.12)nmol/mg,(3.09 ±0.11)nmol/mg and (3.21 ±0.08)nmol/mg;the concentrations of adiponectin were (2.68 ±0.14)μg/mL,(2.80 ±0.07)μg/mL and (2.86 ±0.18)μg/mL.Compared with group Sham,both LOV group and CLP group had increased pulmonary damage:(1)the levels of TNF-α[4h,12h and 24h were (4.23 ± 0.18)pg/mL,(5.62 ±0.24)pg/mL and (5.14 ±0.10)pg/mL,t=28.41,30.98 and 36.62]and IL-6[4h,12h and 24h were (39.12 ±0.17) pg/mL,(47.25 ±0.21) pg/mL and (44.690.27) pg/mL,t =158.90,273.40 and 127.28] of the CLP group in BALF were both increased,and MPO[4h,12h and 24h were (4.85 ±0.13) U/g tissue, (6.17 ±0.08)U/g tissue and (7.84 ±0.10)U/g tissue,t=26.39,79.40 and 60.43]and MDA[4h,12h and 24h were (6.24 ±0.06)nmol/mg,(7.56 ±0.15)nmol/mg and (8.43 ±0.10)nmol/mg,t=53.31,58.86 and 90.06] concentrations in lung homogenate were raised with the decreased expression of serum adiponectin[4h,12h and 24h were (1.35 ±0.10)μg/mL,(1.17 ±0.07)μg/mL and (1.24 ±0.11)μg/mL,t=19.86,12.75 and 18.81](all P<0.05);(2) meanwhile the levels of TNF-α[4h,12h and 24h were (2.85 ±0.17) pg/mL,(3.720.13) pg/mL and (3.240.09)pg/mL,t=12.02、20.73 and 16.68]and IL-6[4h,12h and 24h were (30.75 ±0.22)pg/mL, (37.52 ±0.29)pg/mL and (32.43 ±0.26)pg/mL,t=78.42,68.29 and 83.67]in BALF of the LOV group were all increased,the contents of MPO[4h,12h and 24h were(3.59 ±0.05)U/g tissue,(4.67 ±0.11)U/g tissue and (5.33 ± 0.05)U/g tissue,t=12.03,33.63 and 33.70]and MDA[4h,12h and 24h were (4.45 ±0.10)nmol/mg,(5.01 ± 0.11)nmol/mg and (5.83 ±0.04) nmol/mg,t =17.72,30.23 and 71.75] were also increased with the serum adiponectin concentrations[4h,12h and 24h were (2.09 ±0.08)μg/mL,(2.07 ±0.05)μg/mL and (2.03 ± 0.10)μg/mL,t=8.96,20.79 and 6.30]dicreased(all P<0.05).There were less histopathological changes in the LOV group,and the levels of TNF-α(t=13.46,17.05 and 15.43),IL-6(t=73.70,64.10 and 80.12),MPO(t=22.16,27.01and 32.86) and MDA(t=37.59,42.72 and 59.13) were lower than those in CLP group,also the level of adiponectin(t=14.15,8.10 and 3.19) increased siginificantly(all P<0.05).Conclusion Administration of lovastatin could attenuate lung injury of the sepsis by down-regulate the level of TNF-αand IL-6,with reduced inflam-matory response and oxidative stress,and could upregulate the level of adiponectin in serums of rats with sepsis.

Objective To investigate the clinical treatment of infective endocarditis with vegetations in pregnant women and the outcomes of the gestation. Methods Nine cases of pregnant women diagnosed as infective endocarditis with vegetations in Beijing Anzhen Hospital, Capital Medical University from January 2001 to October 2015 were enrolled in retrospective analysis. Consultations were held by doctors from department of obstetrics, anesthesiology, cardiology, cardial surgery and extracorporeal circulation to decide the individualized treatment plan for the 9 cases of pregnant women after admissions. Clinical treatments including general treatment, anti-infection treatment, cardiac surgery, and termination of pregnancy surgery were completed through collaboration among related departments. The clinical characters, therapeutic regimens, maternal and neonatal outcomes of the 9 cases were analyzed. Results (1)Clinical characters: the ages of the 9 cases of pregnant women were from 25 to 36 years old. The onset gestational ages were from 19 to 36 weeks. Clinical symptoms: fever, cough, sputum and progressive anemia were the main symptoms. Patients had cyanosis of lips, could not lie on the back or even be orthopnea, when heart failure happened. Heart murmur was audible and splenomegaly was touched in physical examination. Blood cultures were positive. Basic heart disease types: 7 cases of congenital heart diseases included 2 cases of aortic insufficiency, 1 case of mitral insufficiency, 1 case of patent ductus arteriosus, 1 case of right ventricular outflow tract stenosis and 2 cases of ventricular septal defect.Two cases of rheumatic heart diseases included 1 case of mitral stenosis, 1 case of mitral stenosis after artificial disc changed and jammed. According to endocardial vegetations attached position there were 3 cases of mitral valve vegetations, 2 cases of pulmonary valve vegetations, 3 cases of aortic vegetations and 1 case of right ventricular outflow tract neoplasm. Preoperative heart function classification:1 case of levelⅡ, 3 cases of levelⅢ, 5 cases of levelⅣ.(2)Treatments:general treatment included oxygen uptake, rest in bed, cardiac strengthen and diuretic therapy, etc. Combined and adequate antibiotics were applied in anti-infection treatment according to drug sensitive test. Nine cases of pregnant women were all performed surgical treatment of heart diseases and removal of the endocardial vegetations. Caesarean sections were performed for 2 cases in second trimester and for 7 cases in last trimester. Cardiac surgery and caesarean section were operated in 6 cases at the same time among 22-34 weeks of pregnancy. Cardiac surgery were respectively operated in 2 cases 11 days and 32 days after the caesarean section at 33, 37 weeks of pregnancy. While Cardiac surgery was operated (at 26 weeks of pregnancy) before the caesarean section (at 37 weeks of pregnancy) in another 1 case. (3) Maternal and neonatal outcomes:7 cases of pregnant women were rescued successfully, while 2 cases of pregnant women were death. Postoperative heart function classification: 1 case of level Ⅰ, 2 cases of levelⅡ, 4 cases of levelⅢand 2 cases of levelⅥ. Neonatal survivals were 6 cases including 2case of full-term infants, 4 cases of preterm infants. Stillbirth or neonatal death were 3 cases, which included 2 cases performed caesarean section in second trimester and 1 case of very low weight infant who was given up treatment by family because of severe asphyxia. Followed up periods were from 1 to 7 years with an average time of (2.0 ± 1.6) years. Infants and young children grew and developed well during the period of follow up. Conclusions The risk is extremely high of pregnancy with infective endocarditis with vegetations. But there is still a way to save the maternal and neonatal life by using a multidisciplinary collaboration formulation and implementation of individualized treatment plan and selecting the appropriate time for heart surgery and the termination of pregnancy.

Abstract: Cell death is a fundamental biological phenomenon that is essential for the survival and development of organisms. Cell death can be either a spontaneous programmed process by the host or an accidentally triggered process. According to the different signaling pathway activated by various stimulates, programmed cell death exhibits the lytic or non-lytic morphology. For example, apoptosis, a typical non-lytic form of cell death, exhibits cell shrinkage and induces the formation of apoptotic bodies. Pyroptosis mediated by cysteine-containing aspartate-specific protease-1/11 (caspase-1/11) and necroptosis can induce inflammatory reactions and promote cell lysis to release inflammatory cytokines via triggering the pore-forming mechanism of the cell membrane, representing a typical modes of lytic cell death. In addition, the release of reactive oxygen species caused by the damaged mitochondria may further trigger ferroptosis during the pathogen infection. Programmed cell death can play an immune defensive role by eliminating infected cells and intracellular pathogens and stimulating the innate immune response through the resulting cell corpses. Here, we discuss the molecular mechanisms of five programmed cell death pathways: apoptosis, pyroptosis, ferroptosis, necroptosis and PANoptosis. We describe their roles in the innate immune defense against bacterial infections and give a brief statement of the interactions between the different programmed cell death, hoping to provide new insights for in-depth study of the pathogenic mechanisms of infectious diseases.

Objective To investigate the effects of dexmedctomidine pretreatment and postconditioning on renal ischemia-reperfusion (I/R) injury in rats.Methods Thirty-two male Wistar rats,aged 3-4 months,weighing 220-300 g,were randomly divided into 4 groups ( n =8 each):sham operation group ( group S),I/R group,dexmedetomidine pretreatment group (group Pre) and dexmedetomidine postconditioning group (group Post).The rats were anesthetized with phenobarbital sodium 65 mg/kg.Renal I/R was produced by occlusion of both renal pedicles for 60 min followed by 48 h reperfusion.Dexmedetomidine 50 μg/kg was given intraperitoneally at 30 min before ischemia and at the beginning of reperfusion in Pre and Post groups respectively.The concentrations of serum creatinine and blood urea were determined at 0,24 and 48 h of reperfusion (T1-3).The renal tissues were obtained at the end of reperfusion for microscopic examination and detection of apoptosis by TUNEL assay.Acute kidney tubular necrosis was scored and apoptosis index (AI) was calculated.Results Compared with group S,the concentration of serum creatinine and blood urea at T2.3,and acute kidney tubular necrosis score and AI were significantly increased in I/R,Pre and Post groups ( P ＜ 0.05).Compared with I/R group,the concentration of serum creatinine and blood urea at T2.3,acute kidney tubular necrosis score and AI were significantly decreased in Pre and Post groups ( P ＜ 0.05).Conclusion Both dexmedetomidine pretreatment and postconditioning can attenuate renal I/R injury through inhibition of cell apoptosis in rats.

Objective To evaluate the effects of rapamycin combined with rosiglitazone on lung injury in septic rats.Methods One hundred and twenty healthy male Wistar rats were randomly divided into 5 groups (n =6 each):sham operation group (group S); cecum ligation and punture (CLP) group; rapamycin group (group RPM) ; rosiglitazone group (group RGZ) ; rapamycin plus rosiglitazone group (group RPM + RGZ).The rats were anesthetized with intraperitoneal 10% chloral hydrate 100 mg/kg.Sepsis was induced by CLP in groups CLP,RPM,RGZ and RPM + RGZ.At 30 min before CLP,rapamycin 0.4 mg/kg was injected subcutaneously in RPM group,rosiglitazone 0.3 mg/kg was injected via the femoral vein in RGZ group,and rapamycin 0.4 mg/kg was injected subcutaneously and rosiglitazone 0.3 mg/kg was injected via the femoral vein in group RPM + RGZ.While the equal volume of normal saline was given instead in CLP group.Six rats were sacrificed at 2,6,24 and 48 h after CLP in each group,and lungs were removed and cut into sections which were stained with haematoxylin and eosin and examined under microscope.The pathological changes of lungs were scored.The myeloperoxidase (MPO) activity and signal transducer and activator of transcription 3 (STAT3)-DNA binding activity in lung tissues were measured.Results Compared with group S,the pathological scores,MPO activity and STAT3-DNA binding activity were significantly increased in groups CLP,RPM,RGZ,RPM + RGZ (P ＜ 0.05).The pathological scores,MPO activity and STAT3-DNA binding activity were significantly lower in groups RPM,RGZ and RPM +RGZ than in group CLP,and in group RPM + RGZ than in groups RPM and RGZ (P ＜ 0.05).Conclusion Rapamycin combined with rosiglitazone offers additional benefit to attenuating lung injury induced by sepsis over rapamycin or rosiglitazone alone,and inhibition of activation of STAT3 pathway is involved in the mechanism.

Objective To study the impact of severe idiopathic pulmonary arterial hypertension (IPAH) on pregnancy outcome and to investigate the effect of multidisciplinary approach during pregnancy on the pregnancy outcome in pregnant woman with severe IPAH.Methods Between March 2007 and November 2013,10 pregnant women with severe IPAH undergoing treatment in Beijing Anzhen Hospital were studied retrospectively.Hemodynamic measurements,medical therapy,manner of delivery,anesthetic administration,multidisciplinary management and outcomes were assessed.Results All 10 cases were first diagnosed at the mean of (24 ± 3) weeks during the pregnancy.The systolic pulmonary artery pressure (sPAP) estimated by transthoracic echocardiography was (95.6 ± 1.3) mmHg (1 mmHg =0.133 kPa).Seven cases of class Ⅲ and 3 cases of class Ⅳ were recorded by World Health Organization functional class.One patient underwent pregnancy termination at gestational age of 21 weeks with no maternal death or complications,nine patients continued pregnancy and all the patients underwent cesarean section.The mean pregnancy length was (31 ± 5) weeks.Nine had cesarean deliveries during continuous epidural anesthesia,and one during general anesthesia.There were three maternal deaths in hospital (5,2,3 days postpartum),and seven patients were alive,and the average hospitalization days was (8 ± 4) days.One fetus lost with cesarean section.Two were term delivery,and seven cases were premature delivery.The average weight is (1 948 ± 731) g and nine were alive and no malformation.Conclusions Because of maternal mortality in patients with severe IPAH remains prohibitively high,patients should continue to be counseled to avoid pregnancy.Women with severe IPAH who become pregnancy should be followed by multidisciplinary approach,and cesarean deliveries during continuous epidural anesthesia are a relatively safe way for pregnancy termination in patients with severe IPAH.