Objective To establish adriamycin-induced focal segmental glomerular sclerosis(FSGS) mice model,and observe the expressions of and relation between oxidative stress and p38 MAPK signal pathway in renal injury.Methods Eight-week-old male Balb/c mice were randomly divided into FSGS group (n=20) and control group (n=20).In FSGS group mice were intravenously injected with a single dose of adriamycin (0.01 rag/g),and mice in control group were received saline with the same dose.At day 3,7,14,22 and 32,urine protein-to-urine creatinine ratio (P/C) was detected.At day 22 and 32,serum creatinine,blood urea nitrogen,nitric oxide (NO) and reactive oxygen species (ROS) in blood and urine,and ROS in kidney tissues were detected;changes of pathological morphology in renal tissue were analyzed by HE stain;the expressions of NF-κB,CD36,IL-13,BAX and Bcl-2 mRNA were detected by real time quantitative PCR;the expressions of NF-κB,p-p38 and p-ERK1/2 protein were detected by Western blotting.Results Compared with that in control group,P/C was gradually increasing in FSGS group,and peaked at day 22 (P ＜ 0.05).At day 22 and 32,mice had higher creatinine,serum creatinine,urea nitrogen,ROS and NO in FSGS group than those in control group (all P ＜ 0.05).There were mild hyperplasia of mesangial cells and mesangial matrix,segment with moderate exacerbations,podocytes with significant proliferation,and the capillary loops of the stenosed in the glomerular in FSGS group at day 32.Compared with those in control group,the mRNA expression of NF-κB,BAX,IL-13 and CD36,and the protein expressions of NF-κB and p-p38 MAPK were gradually increased in FSGS group,all showed statistical differences at day 32 (all P＜ 0.05);the expression of p-ERK1/2 was increased at day 22 (P ＜ 0.05) but was reduced at day 32 (P ＜ 0.05).Conclusions Adriamycin has induced FSGS in mice successfully,which may through oxidative stress activating p38,up-regulating NF-κB,increasing the inflammatory cytokines and inducing apoptosis pathways.

AIM:To investigate whether mitochondrial membrane potential (ΔΨm ) and the mitochondrial ap-optotic pathway are involved in the protective mechanism of Panax quinquefolium saponin ( PQS) against cardiomyocyte ap-optosis after ischemia/reperfusion ( I/R) injury in rat myocardium .METHODS: Ninety healthy male SD rats were ran-domly divided into sham group , I/R group, PQS (200 mg· kg -1 · d-1 ) +I/R group, cyclosporine A ( CsA) group, CsA (10 mg· kg-1 ) +I/R group and PQS +CsA +I/R group.The model of myocardial I/R injury in vivo was established by ligating the left anterior descending artery ( LAD) for 30 min followed by 120 min of reperfusion in the rats .The serum ac-tivity of lactate dehydrogenase ( LDH ) was measured by automatic chemistry analyzer .The myocardial infarct size was measured by Evans blue and 2,3,5-triphenyltetrazolium chloride (TTC) staining.Cardiomyocyte apoptosis was detected by in situ TDT-mediated dUTP nick end labeling (TUNEL).The protein levels of Bcl-2, Bax, cleaved caspase-3 and cytosol-ic cytochrome C were determined by Western blotting .ΔΨm was measured by laser scanning confocal microscopy and fluo-rescence microplate reader .RESULTS:Compared with I/R group, the serum content of LDH ,the infarction size in PQS+I/R group, CsA+I/R group and PQS +CsA+I/R group and the myocardial apoptotic index were decreased .Compared with I/R group, the fluorescence intensity of mitochondria after JC-1 staining was enhanced in PQS +I/R group, CsA+I/R group and PQS+CsA+I/R group, and the relative fluorescence units (RFU) ofΔΨm were improved in those 3 groups. In PQS+I/R group, CsA+I/R group and PQS+CsA+I/R group, the protein expression of Bcl-2 was increased, and that of Bax was decreased compared with I/R group.Moreover, in those 3 groups, the protein levels of cleaved-caspase-3 and cytosolic cytochrome C were decreased compared to I /R group, respectively.CONCLUSION:PQS attenuates myocardial injury and cardiomyocyte apoptosis during I /R, and the protective mechanisms of PQS were associated with the modulation ofΔΨm and the inhibition of mitochondrial apoptosis pathway .

Objective To observe the effect of out-hospital standardized treatment on the recurrence of the first onset of acute unprovoked pulmonary thromboembolism (PE) after discontinued anticoagulant therapy or during anticoagulation therapy in PE patients after treatment and discharged from hospital.Methods A prospective study of patients with acute PE admitted into emergency ICU for training in out-hospital standardized anticoagulation treatment was carried out from January 2015 to December 2016 (observation group).Another cohort of EP patients without training in out-hospital standardized anticoagulation treatment admitted from January 2010 to December 2014 was enrolled for retrospective analysis(control group).The out-hospital standardized anticoagulation treatment strategy included the guidance of anticoagulation therapy,record all of the patients' symptoms related with recurrent EP both during and discontinuous anticoagulant treatment,V/O scan at 3 months,6 months and 12 months follow-up,respectively.The patients with ceased anticoagulant therapy would be followed up for at least one year.Patients with signs of recurrence would have a definite diagnosis at once.The anticoagulation status and outcome of the patients in control group found in out-patient department were recorded.Results ① There were 129 patients with acute unprovoked PE in observation group and 246 in control grouThere were no significance difference both in mean age and gender between two groups (P ＜0.05).② Recurrence rate was 11.63％ in observation group and 22.36％ in control group (P ＜0.01);③ There was significance difference in mortality rate between observation group (3.1％) and control group (10.85％) (P ＜0.05).There was also significant difference in rate of missing follow-up between observation group (10.85％) and control group (21.54％) (P＜0.001),and.there was significant difference in rate of discontinuous anticoagulation therapy between observation group (1.55％) and control group (8.5％) (P ＜0.01).④ There was no significance difference seen in the rate of patients exposed to multiple risk factors of arteriosclerosis between observation group (82.25％) and control group (77.64％) (P＜0.05).But the target rate of controlling various risk factors of arteriosclerosis was 79.31％ in observation group and 54.97％ in control group respectively (P＜0.05).Conclusions Standardized treatment can effectively reduce the recurrent rate of the venous episodes of the patients with first episode of acute unprovoked pulmonary thromboembolism;Recurrent venous episodes of the PE patients who exposed to the multiple risk factors of arteriosclerosis require more attentions.

Objective:To assess the risk of venous thromboembolism (VTE) and anticoagulation-related bleeding of acute critical emergency patients staying in the emergency department at least 72 h, so as to improve the ability of emergency physicians to identify risk factors of VTE and their awareness of safety prevention in these patients.Methods:Multicenter emergency internal medicine patients meeting the inclusion criteria at the same time were collected. Padua and Caprini scores were used to evaluate the risk of VTE and the HAS-BLED score was used to assess the risk of anticoagulation-related bleeding.Results:A total of 930 emergency patients from 7 medical centers were enrolled in our study from January 15, 2021 to March 15, 2021. The proportion of high-risk population with VTE was 50.22% with Padua score and 78.49% with Caprini score, respectively. The proportion of high-risk bleeding (HAS-BLED score) was 40.43%.Conclusions:More than half of the acute critical ill patients who stay in emergency department for more than 72 h are at high risk of VTE. This group of patients have a relatively low risk of anticoagulation-related bleeding.

Objective:To develop an occupational internal driving force measurement scale for general practitioners receiving residency training, and to investigate its reliability and validity.Methods:A pool of items was constructed for the scale based on the literature analysis and qualitative interview results of occupational internal driving force and the current development status of general practitioners, and then expert Delphi consultation was conducted to form the initial version of the scale. A questionnaire survey was conducted among 403 general practitioners to test the reliability and validity of the scale.Results:There were 11 items in the occupational internal driving force scale for general practitioners receiving residency training, which were divided into three dimensions. The scale had a Cronbach's α coefficient of 0.945, and each dimension had a Cronbach's α coefficient of above 0.850; the KMO coefficient of the Bartlett's sphericity test was 0.925. The factor analysis showed that all items had a factor load of ≥0.4 and a commonality of >0.2, and thus 11 items were retained. Three common factors were extracted by the factor analysis and the correlation analysis showed a correlation coefficient of >0 between the common factors of the total score of the scale and a significant positive correlation ( P<0.01). Based on the contents, theoretical research, and expert suggestions of each factor, they were named subject affiliation, development expectations, and identification needs, which contained 3 items, 3 items, and 5 items, respectively. Conclusions:The occupational internal driving force scale for general practitioners receiving residency training has a reasonable structure and good reliability and validity and is suitable for evaluating the occupational internal driving force of general practitioners, which provides guidance for the vocational education of residents.

Background Research on non-target organ damage of biological pesticides has attracted much attention. Rotenone exposure may be far beyond the occupational environment, and the exposureduring pregnancy may be increased through bioaccumulation, fruit or vegetable residues, and other forms of oral intake. At present, the effects of rotenone on placental development and its mechanism are still unknown. Objective To investigate the developmental damage of rat placenta and evaluate the expression levels of glycogen synthase kinase (GSK-3β) and beta catenin (β-catenin) followed by rotenone exposure through the placental barrier during pregnancy, as well as to propose possible associated mechanisms. Methods Eighteen sexually mature SD female infertile rats without specific pathogens were selected and divided into three groups: blank control group (0.9% saline), corn oil group, and rotenone group (corn oil + 2 mg·kg⁻¹ rotenone) by random number method, six female animals in each group. Another six male rats were selected and mated to the female rats at night with a female to male ratio of 3:1 per cage. Pregnant rats were given 0.9% saline, corn oil, and 2 mg·kg⁻¹ rotenone preparation by isovolumetric gavage once daily for the entire gestation period (19 d), and their conditions were observed after the last dose. The pregnant rats were anesthetized, and the size of the placenta and blood perfusion were detected by ultrasound the next day of the last dose of rotenone. Then, 3 pregnant rats in each group were sacrificed immediately and the placenta and umbilical cord tissues were dissected. The remaining 9 pregnant rats gave birth naturally, and the fetuses were observed for developmental evaluation and weighed. The histopathological changes of umbilical cord and placenta were observed by hematoxylin-eosin staining. The reactive oxygen species levels of placenta tissues were detected by flow cytometry. The Ca²⁺-ATPase activity of placenta tissues was detected by colorimetric method. The localization and levels of GSK-3β and β-catenin expression of placenta were detected by immunohistochemistry. The p-GSK-3β/GSK-3β and p-β-catenin/β-catenin protein expression in placental tissues were measured by Western blotting. Results No injury or death was recorded during the pregnant rats receiving rotennon administration. Adverse pregnancy outcomes such as fetal absorption and postpartum stillbirth were found in the rotenone group, and the weight of the fetal mice decreased (P<0.05). The B-ultrasound showed disc-shaped placenta with a thick middle and thin edge, smooth fetal surface, rough maternal surface, visible placental lobules, granular echotexture of the placenta with comma-like echogenic densities, and chorionic plate showing deep indentations, no calcification, degeneration, or necrosis in each group. Compared with the corn oil group, the fetal surface diameter of the placenta was reduced in the rotenone group (P<0.05). The Doppler color ultrasound showed that interplacental blood flow was reduced in the rotenone group, while interplacental blood flow was abundant in the blank control and the corn oil groups. The hematoxylin-eosin staining results showed that smooth muscle cells in the umbilical cord tissues of rats were loosely arranged, with fuzzy nuclei and inflammatory infiltration in the rotenone group. The placental trophoblast cells were small in size, disorderly arranged with nuclear fragmentation and cytoplasm turbidity. The tissue reactive oxygen species level in the rotenone group was higher than those in the other two groups (P<0.05). The Ca²⁺-ATPase activity of placental tissues was reduced in the rotenone group (P<0.05). The immunofluorescence low-magnification observation showed that GSK-3β and β-catenin were expressed in placental tissue, weak fluorescence expression in the decidua basalis, strong fluorescence expression in the labyrinthine layer structure. The labyrinthine layer under high magnification showed that compared with the blank control group and the corn oil group, the brightness of β-catenin fluorescence expression in the rotenone group decreased (P<0.05), and the brightness of GSK-3β expression increased (P<0.05). The Western blotting results showed that the expression of β-catenin and p-GSK-3β proteins decreased (P<0.01), and the expression of GSK-3β protein increased (P<0.01) in the rotenone group. No significant expression of p-β-catenin protein was detected in the placenta tissue of each group. Conclusion Rotenone exposure during pregnancy induces placental hypoperfusion, growth retardation, and oxidative stress in rats, as well as down-regulation of β-catenin and p-GSK-3β protein expression, and up-regulation of GSK-3β protein expression, which may further lead to abnormal pregnancy and fetal restricted growth.

Objective:To investigate the risk factors for death in children with severe adenovirus pneumonia (SAP) in pediatric intensive care unit (PICU), and to provide reference basis for clinical reasonable treatment and reducing the adverse outcome.Methods:The clinical data of 68 children with SAP hospitalized in PICU, Children′s Hospital of Chongqing Medical University from August 2018 to September 2019 were retrospectively analyzed.They were divided into the death group and the survival group according to their condition.The age, basic diseases, complications and laboratory examination results of children were collected for univariate analysis, and multivariate Logistic regression analysis was performed for those with significant univariate analysis. Results:Among the 68 children with SAP, 50 were males and 18 were females, and 46 cases (67.6%) aged between 6 months and 2 years.Fifty-five cases(80.9%) of SAP occurred in spring and summer.There were 61 cases (89.7%) with the spike over 39 ℃ and 21 cases (30.9%) had fever for over 2 weeks; 42 cases (61.8%) were infected with mixed other pathogens.Intrapulmonary and extrapulmonary complications at varying severity were observed.There were 23 cases (33.8%) deaths.Univariable Logistic regression analysis showed that the rates of congenital heart disease(13 cases vs. 9 cases), alanine transaminase >100 U/L(12 cases vs. 8 cases), acute respiratory distress syndrome (ARDS)(13 cases vs. 9 cases) and severe extrapulmonary complications (19 cases vs. 14 cases) were significantly higher in the death group than those in the survival group (all P<0.05). Multivariate Logistic regression analysis showed that congenital heart disease, ARDS and severe extrapulmonary complications were independent risk factors for death in children with SAP (all P<0.05). Conclusions:Children with SAP in PICU are mostly 6 months to 2 years old.SAP mainly occurs in spring and summer, which is featured by the high spike of fever, long duration of fever, easy to be infected with other pathogens, high incidences of systemic complications, and high mortality.The combination of congenital heart disease, ARDS and severe extrapulmonary complications increases the risk of death in children with SAP in PICU.

Pyroptosis is a kind of inflammatory cell death mediated by the Gasdermin family,which has made great progress in tumor therapy in recent years.Basing on that cell pyroptosis can activate the anti-tumor immune response,and tumor immunotherapy is a new field of tumor therapy,the regulation of cell pyroptosis exhibits great potential for tumor therapy.Meanwhile,nanotechnology is the key means of tumor precision treatment with the advantages of precise targeting and continuous release.Based on these current situations,this paper summarizes the drugs that activate pyroptosis and the nanocarriers that use nanotechnology to promote pyroptosis to participate in tumor therapy,and summarizes the mechanism and application of their action on pyroptosis.This paper is aimed to provide certain references for anti-tumor therapy based on pyroptosis.