Objective To investigate the protective effect of Guanxinning(GXN)tablet on dilated cardiomyopathy(DCM),and to explore its effect and mechanism in pyroptosis of cardiomyocytes via the NLRP3/ASC/Caspase-1 pathway.Methods Rats were divided into GXN low-dose,GXN high-dose,digoxin,model control,and normal control groups.The DCM model was induced by multiple intraperitoneal injections of 17.5 mg/kg doxorubicin(DOX).The drug was administered at the same time as the model was established for 10 weeks.After the last administration,echocardiography was used to assess cardiac function indexes.After sacrificing the rats,serum was collected to measure IL-1β and IL-18 levels.RT-PCR was used to detect mRNA expression of NLRP3,ASC,Caspase-1,NF-κB,TXNIP,IL-1β,and IL-18.Immunohistochemistry and immunofluorescence staining and Western Blot were used to assess NLRP3,ASC,Caspase-1,IL-1β,and IL-18,GSDMD and GSDMD-NT protein,and TUNEL staining result.Changes in the microstructure of cardiomyocytes were observed by transmission electron microscopy.Results Compared with the normal control group,IVSs,IVSd,LVPWs,FS,SV,EF,and HR of the model control group were significantly reduced,LVIDs,ESV,and serum IL-1β and IL-18 were significantly increased,NLRP3,ASC,Caspase-1,NF-κB,TXNIP,IL-1β and IL-18 mRNA expression was significantly increased,and NLRP3,ASC,Caspase-1,IL-1β,IL-18 and GSDMD-NT protein expression and the TUNEL staining area were increased significantly,and the microstructure of cardiomyocytes changed significantly.Compared with the model control group,GXN significantly increased IVSs,SV,FS,EF,and HR,significantly reduced LVIDs,ESV,and the serum levels of IL-1β and IL-18,and reduced NLRP3,ASC,Caspase-1,NF-κB,TXNIP,IL-1β,and IL-18 mRNA expression,NLRP3,ASC,Caspase-1,IL-1β,IL-18 and GSDMD-NT protein expression,and the TUNEL staining area.Additionally,the microstructure was improved significantly.Conclusions GXN alleviates cardiomyocyte pyroptosis in rats with DCM by inhibiting the NLRP3/ASC/Caspase-1 pathway.

Objective To study the effects and mechanisms of Smilax glabra flavonoids(SGF)on myocardial hypertrophy and cardiac inflammation induced by isoproterenol(ISO)in mice.Methods C57/6J mice were randomly divided into a normal group,ISO model group(1.25 mg/(kg·d)),SGF low-dose group(50 mg/(kg·d)),and SGF high-dose group(100 mg/(kg·d)).The SGF groups were given prophylactic SGF for 7 days before modeling,then subcutaneous ISO injection was given to each group,and echocardiography was performed after continuous injection for 7 days.Serum was separated from orbital blood,and the NT-proBNP and inflammatory factor(IL-1β,IL-6,and TNF-α)contents of the blood were detected.Myocardial specimens were collected,and pathological changes to myocardial tissue were observed.Myocardial ROS levels were detected by DHE staining.The mRNA levels of heart-related hypertrophy genes and changes in the expression of key proteins in the inflammatory pathway of NLRP3/Caspase-1/IL-18 in myocardial tissue were detected.Results SGF prophylactic administration decreased IVSd,IVSs,and EF in echocardiography and increased LVIDs,LVIDd,and LVESV.The IL-1 β,IL-6,TNF-α,and NT-proBNP contents of blood decreased,and the mRNA expression levels of the heart-related hypertrophy genes for ANP,BNP,and β-MHC were subdued.The increase in myocardial ROS levels was also inhibited.The protein expression of NLRP3,Caspase-1(p20),and IL-18,which are key factors in the NLRP3/caspase-l/IL-18 inflammatory pathway,was down-regulated in myocardial tissue.The hypertrophy and disordered arrangement of cardiomyocytes were improved,the increase in fibroblast numbers outside myocardial fibers was reduced,and the infiltration of inflammatory cells and fibrosis of myocardial tissue were alleviated.Conclusions SGF can improve ISO-induced myocardial hypertrophy and cardiac inflammation in mice and may act through the NLRP3/Caspase-1/IL-18 inflammatory pathway.

Objective:To analyze the early warning value of laboratory examination on admission of patients with hemorrhagic fever with renal syndrome to critically ill patients.Meetods:In this study, a retrospective case-control study was used to analyze the clinical data and laboratory examination results of patients with hemorrhagic fever with renal syndrome admitted to the emergency department of Tangdu Hospital of Air Force Medical University from January 2021 to January 2022. According to the patient's laboratory indexes and clinical symptoms, the patients were divided into mild, moderate, severe and critical groups. The general data of the two groups were compared, and the independent risk factors of critically ill patients were screened by multi-factor logistic regression analysis, the predictive model of severe HFRS patients was constructed, and the ROC curve was drawn. .Results:Of the 164 patients with HFRS, 50 were in the severe group and 114 in the mild group. The serum levels of WBC, AST, ALT, Cr, BUN, DD and PCT in the severe group were higher than those in the mild group, while the levels of PLT, ALB and PTA in the severe group were lower than those in the mild group. Multiple logistic regression analysis showed that WBC, PLT and PCT were independent influencing factors for the progression of critically ill patients. The predictive model of severe HFRS was established as follows: logit (P) = -0.321 + 0.040 WBC (×10 9/L) -0.045 PLT (×10 9/L) + 0.086 PCT(ng/mL). The early warning ef?cacy of WBC, PLT, And PCT for severe HFRS was further analyzed. The area under the ROC curve (area under curve, AUC) was 0.779, 0.842, 0.862, and the optimal threshold was 10.435×109/L, 41.5 ×109/Land 2.97 ng/mL, respectively. The AUC of joint detection is 0.900, the sensitivity is 88.0%, and the speci?city is 82.5%, which is better than that of a single laboratory. . Conclusions:HFRS laboratory indexes have certain clinical signi?cance for the identi?cation of critically ill patients, in which serum WBC, PLT and PCT indexes are the risk factors of severe HFRS, which provides a theoretical basis for clinical diagnosis, treatment and prognosis of severe HFRS patients.

Background: At present, clinical dilemma remains to be solved in terms of therapy-choices for specific locally advanced cervical cancer (LACC) patients: 1) Although concurrent chemoradiotherapy (CCRT) is recommended as the first choice for them, many patients, influenced by the Chinese culture, prefer to choose radical surgery (RS) as their primary treatment. The difference between the 2 therapies in improving patient prognosis is still unknown. 2) Laparoscopy has been questioned since the noted Laparoscopic Approach to Cervical Cancer trial. Nevertheless, clinical research on laparoscopic surgery under the strict tumor-free principle is still underway globally, therefore whether laparoscopic surgery can be used for specific LACC is also an urgent issue to be explored. Methods A multi-center, randomized controlled study is designed to investigate the effect of different treatment strategies on the prognosis and quality of life (QoL) in patients with specific locally LACC. A total of 402 patients will be enrolled over a period of 3 years. Eligible patients will be randomized (3:1) to either RS group or CCRT group. Patients assigned to RS group will be randomized (1:2) to the abdominal RS group or laparoscopic RS group. All patients will then be followed-up for 5 years. The primary end point is the 2-year progression-free survival (PFS). The secondary end points include 5-year PFS, 2-year overall survival (OS), 5-year OS, adverse events caused by RS or CCRT and QoL.

Objective: To analyze the diagnostic value of ultrasound guided 14 gauge coreneedle biopsy (US-CNB) in breast nodules. Methods: We retrospectively analyzed the pathological results of US-CNB and surgical excision from 373 breast nodules in Peking University International Hospital from Sep 2016 to Nov 2018 to evaluate the accuracy of 14g US-CNB. Results: A total of 349 patients(373 nodules)underwent US-CNB. US-CNB reported 282 benign lesions(75.6%, 282/373), 20 high-risklesions(5.4%, 20/373), and 71 malignant lesions(19.0%, 71/373). For 282 CNB reported benign lesions, the surgical pathology confirmed 235 lesions , 46 for high-risk lesions and 1 for malignant lesion with a concordancy of 83.3%(235/282)and the underestimation rate was 16.7%(47/282). US-CNB identified 20 high-risk lesions. According to surgical results, 15 were high-risk lesions and 5 were malignant lesions with a concordancy of 75% (15/20)and the underestimation rate was 25%(5/20). When it comes to malignant lesions, the excision results showed that 70 were malignant lesions and 1was high-risk lesion with a concordancy of 98.6%(70/71)and the overestimation rate was 1.4%(1/71). The concordance of the histological type , calculated for 50 invasive carcinomas, was 92% (46/50) with a kappa value of 0.77.The concordance of the histological grade could be calculated for 38 invasive ductal carcinomas with the Elston-Elllis Method . It was 89.5% (34/38) with a kappa value of 0.57. Conclusions The pathology result of 14gUS-CNB is in good consistency with surgical excision for breast benign and malignant lesions.

Objective To investigate the clinical features and antimicrobial susceptibility of neonatal Listeria septicemia.Methods Eleven cases of neonatal Listeria septicemia that were treated in the Huzhou Maternity and Children Health Hospital from March 2013 to March 2017 were enrolled in this study.Clinical data including the results of bacterial culture,antimicrobial susceptibility test and antibiotic treatment were collected and retrospectively analyzed.Moreover,maternal history of Listeria monocytogenes (LM) infection before delivery was retrieved.Results All of the 11 mothers had fever before delivery and nine of them showed different grades of amniotic fluid contamination during delivery.Clinical symptoms of the 11 neonates included dyspnea (11 cases),fever (ten cases),apnea (nine cases),slow response and feeding difficulty (nine cases),convulsion (six cases),vomiting and abdominal distension (two cases),pulmonary hemorrhage (one case),progressive jaundice (one case) and systemic skin bleeding point (one case).All cases showed abnormal results of blood routine test and increased calcitonin and C-reactive protein.Ten cases received cercbrospinal fluid examination,seven of which were abnormal.Altogether 17 strains of LM were isolated from various specimens.These strains were all sensitive to piperacillin-tazobactam,ampicillin-sulbactam,meropenem,vancomycin,cotrimoxazole,ciprofloxacin and gentamycin,but resistant to oxacillin.Strains those were sensitive to penicillin,ampicillin,erythromycin and clindamycin accounted for 10/17,11/17,9/17 and 8/17,respectively.The 11 neonates were treated with piperacillin-tazobactam,meropenem or vancomycin.All of them improved (11/11)and ten were cured (10/11).All cases were followed up through phone calls at one week and one month after discharge.Two were lost to follow-up,while thc others were all in good condition.Conclusions Neonatal Listeria septicemia is usually a severe disease characterized by rapid progression and mainly presented with dyspnea and fever,besides there is a high possibility of purulent meningitis.Some LM strains are resistant to single-agent penicillin antibiotics.However,antibiotics such as piperacillin-tazobactam,meropenem and vancomycin are effective in the treatment of neonatal Listeria septicemia.

Objectives To understand the effects of different doses of vitamin D supplementation on serum calcium,phosphorus,alkaline phosphatase and 25-hydroxyvitamin D levels in very low birth weight infants (VLBWI) and to provide guidance for early prevention of metabolic bone disease in VLBWI.Methods A total of 90 VLBWI hospitalized in the Department of Neonatology,Huzhou Maternal and Child Healthcare Hospital between January 2014 and January 2016 were enrolled and randomly divided into two groups:highdose group and low dose group.High-dose group was given vitamin D 900 U/d orally and low-dose group was given 400 U/d since the eighth day after birth.Serum calcium,phosphorus and alkaline phosphatase levels were detected at 1,7,21 and 42 days of age and serum 25-hydroxyvitamin D levels were detected at 7,21and 42 days of age.Two-sample t-test,Chi-square test,one-way analysis of variance and LSD or Dunnett's T3 test were used for statistical analysis.Results No significant differences in serum calcium,phosphorus and alkaline phosphatase levels were found between the two groups at 1 and 7 days of age,nor were found in serum 25-hydroxyvitamin D level at 7 days of age (all P＞0.05).At 21 days of age,high dose group had higher serum calcium,phosphorus and 25-hydroxyvitamin D levels than low-dose group [(2.38 ± 0.09) vs (2.04 ± 0.15) mmol/L,t=2.421;(1.80±0.50) vs (1.71 ±0.60) mmol/L,t-0.637;(45.58± 18.43) vs (42.53± 16.33) nmol/L,t=0.421],but lower alkaline phosphatase level [(505.12± 185.61) vs (588.32± 168.72) U/L,t=5.314] (all P＜0.05).The same trends were found at 42 days of age.In high-dose group,serum calcium level increased at 7,21 and 42 days of age as compared with that at 1 day of age [(2.43±0.13),(2.38±0.09),(2.39±0.08) vs (2.06±0.57) mmol/L];serum phosphorus level at 7 days of age was lower than that at 1,21 and 42 days of age [(1.31 ±0.26) vs (1.89±0.39),(1.80±0.50),(1.98±0.30) mmol/L];serum alkaline phosphatase level at 7,21 and 42 days of age was higher than that at 1 day of age [(475.18± 133.73),(505.12± 185.61),(538.43 ± 168.16) vs (296.15 ± 99.41) U/L] and a significant increase was observed at 42 days of age as compared with that at 7 days of age;serum 25 hydroxyvitamin D level at 21 days of age was higher than that at 7 days of age,and that at 42 days of age was higher than that at 7 and 21 days of age [(73.55±23.65) vs (30.63± 12.66) and (45.58 ± 18.43) nmol/L];the differences were all statistically significant (LSD or Dunnett's T3 test,all P＜0.05).Conclusions Vitamin D supplementation from the eighth day after birth can improve calcium and phosphorus metabolism in VLBWI and the dose of 900 U/d is more effective than 400 U/d.

Objective To study the expressions of cysteinyl aspartate specific proteinase 3 ( Caspase 3 ) and proliferating cell nuclear antigen ( PCNA ) in intestinal tissue of neonatal rats with necrotizing enterocolitis ( NEC ) , and the protective effect of glutamine ( Gln ) on NEC. MethodsThirty-six neonatal Sprague-Dawley ( SD) rats were randomly assigned into 3 groups at 48 h after birth (12 in each group). The control group were fed with milk replacer. The NEC group were fed with milk replacer and experiencing cold exposure after hypoxic-reoxygenation twice a day for 3 days, The Gln+NEC group were fed with milk replacer plus Gln and experiencing cold exposure after hypoxic-reoxygenation twice a day for 3 days. All the rats were sacrificed and intestinal tissues obtained at day 3 of the establishment of model. The histological changes of ileal tissues were studied using hematoxy lin-eosin ( HE ) staining. The expressions of Caspase 3 and PCNA were detected using immunohistochemical(IHC)method.Results Caspase3expressioninNECgroup(77.3±8.6)℅was significantly higher than the control group (18. 9 ± 3. 4)℅ and Gln+NEC group (50. 3 ± 6. 2)℅ ( P<0. 05). Also, Caspase 3 in Gln+NEC group was significantly higher than the control group (P<0. 05). PCNA expression in the NEC group ( 15. 0 ± 1. 9 )℅ was significantly lower than the control group (34. 2 ± 5. 8)℅ and the Gln +NEC group ( 24. 0 ± 3. 9 )℅ ( P <0. 05 ) . PCNA expression in the Gln+NEC group was significantly lower than the control group ( P<0. 05). The pathological score of the intestinal tissues was significantly correlated with Caspase 3 expression ( r = 0. 769, P = 0. 005 ), Caspase3/PCNA ratio (r=0. 835,P=0. 002) and PCNA expression (r= -0. 698, P=0. 014) in the NECgroup.Conclusions Up regulation of Cas pase3 and down regulation of PCNA might be correlated with the process of NEC. Gln might be effective in prevention and healing of NEC by inhibiting apoptosis and promoting cell proliferation.

Abstract] Objective To study the roles of IL-12 and IL-23 in the development of protective im-munity and pathological changes during chlamydial urogenital infection.Methods C57BL/6J wild type (wt) mice and mice deficient in IL-12p35 (IL-12p35 KO) or IL-12p40 (IL-12p40 KO)were inoculated in-travaginally with 1×104 IFU of live Chlamydia muridarum ( C.muridarum) organisms.Half mice of each group were reinfected on day 114 after primary infection.Vaginal swabs were taken every 3 or 4 days to mo-nitor live organism shedding.The mice were sacrificed after 114 or 143 days of primary infection and the va-ginal tract and kidney samples were collected for pathological analysis.The numbers of chlamydial inclusion bodies and bacteria in kidney homogenates were titrated after 100 days of primary infection.Results The infection time courses of mice deficient in either IL-12p35 or IL-12p40 were similar after primary infection, but were prolonged as compared with the wild type mice.All mice regardless of genotypes developed severe pathological damages in upper genital tracts with no significant difference among different groups.Almost all IL-12p40 KO mice and some IL-12p35 KO mice showed pathological changes in kidney samples.No obvious abnormality was observed in any of the kidneys from wild type mice.Neither the age-matched IL-12p35 KO nor IL-12p40 KO mice developed any gross pathological changes in kidney in the absence of chlamydial in-fection.C.muridarum inclusions were detected in kidney samples with gross pathological damages from IL-12p35 KO mice and IL-12p40 KO mice.No inclusions were ever detected in kidneys from the wild type mice.The numbers of chlamydial inclusions in the IL-12p40 KO mice were much higher than those of the IL-12p35 KO mice.Live bacteria were detected in mice deficient in either IL-12p35 or IL-12p40, but not in the wild type mice.No significant difference with the number of live bacteria was found between IL-12p35 KO mice and IL-12p40 KO mice.Conclusion IL-12 and IL-23 could inhibit the spread of C.muridarum in-fection from genital tract to kidney.The deficiency of IL-12 or IL-23 might relate to the renal lesions induced by Chlamydia infection.

ObjectiveTo investigate the effect of Glutamine (Gln) on the expression of PCNA in intestinal tissue of neo-natal rats with necrotizing enterocolitis (NEC), and to explore the protective mechanism of Gln in intestinal mucosa.Methods Forty-eight neonatal rats at the age of 48 hours were selected, and divided into 4 groups, control group, Gln group, NEC group, NECGln group. Each group had 12 rats. Control group were fed mice milk substitutes; Gln group were fed mice milk substitutes mixed with Gln; NEC group were fed mice milk substitutes and had cold/ hypoxia exposure twice a day for 3 days; NECGln group were exposed to cold stress, hypoxia and treated with Gln mixed in the milk. The expression of PCNA was detected using immunohistochemical method.Results Compared with control group were and Gln group, the general condition was worse, and the weight was decreased in NEC and NECGln group. The inifltrated inlfammatory cells, congestion, edema, intrinsic layer separation were observed in intestinal mucosa in NEC and NECGln group. The intestinal villus was lost in severe in NEC and NECGln group. The PCNA index was 34.17±5.78, 34.42±5.38, 15.00±1.94, 30.67±3.14 in control, Gln, NEC and NECGln group respectively, with signiifcant difference between each groups (H=24.32,P=0.000). The expression of PCNA in NEC group was lower than that in normal, Gln, and NECGln group (P<0.008). The expression of PCNA had no signiifcant difference among normal, Gln, and NECGln group (P>0.008).Conclusions The expression of PCNA in intestinal mucosa was decreased in NEC rats. Gln supplement could raise the expression of PCNA in intestinal mucosa of NEC rats, and accelerate the speed of intestinal mucosa repair.