Aim To investigate the mechanism of py-roptosis mediated by the NLRP3/caspase-1/GSDMD signaling pathway and the intervention effect of Radix Angelica Sinensis and Radix Astragalus ultrafiltration extract(RAS-RA)in radiation-induced pulmonary fi-brosis.Methods Fifty Wistar rats were randomly di-vided into five groups,with ten rats in each group.Ex-cept for the blank control group,all other groups of rats were anesthetized and received a single dose of 40 Gy X-ray local chest radiation to establish a radiation-in-duced pulmonary fibrosis rat model.After radiation,the rats in the RAS-RA intervention groups were orally administered doses of 0.12,0.24 and 0.48 g·kg-1 once a day for 30 days.The average weight and lung index of the rats were observed after 30 days of contin-uous administration.Hydroxyproline(HYP)content in lung tissue was determined by hydrolysis method.The levels of IL-18 and IL-1 β in serum were detected by ELISA.Lung tissue pathological changes were ob-served by HE and Masson staining.Ultrastructural changes in lung tissue were observed by transmission e-lectron microscopy.The expression levels of NLRP3/caspase-1/GSDMD pyroptosis pathway-related proteins and fibrosis-related proteins in lung tissue were detec-ted by Western blot.Results Compared with the blank group,the HYP content in lung tissue and the levels of IL-18 and IL-1 β in serum significantly in-creased in the model group(P＜0.01).HE and Mas-son staining showed inflammatory cell infiltration and collagen fiber deposition.Transmission electron mi-croscopy revealed increased damaged mitochondria,disordered arrangement,irregular morphology,shallow matrix,outer membrane rupture,mostly fractured and shortened cristae,mild expansion,increased electron density of individual mitochondrial matrix,mild sparse structure of lamellar bodies,partial disorder,unclear organelles,and characteristic changes of pyroptosis.Western blot analysis showed increased expression of caspase-1,GSDMD,NLRP3,CoL-Ⅰ,α-SMA,and CoL-Ⅲ proteins(P＜0.01).Compared with the model group,the RAS-RA intervention group showed signifi-cant improvement in body mass index and lung index of rats,decreased levels of IL-18 and IL-1 β inflammatory factors(P＜0.01),improved mitochondrial structure,reduced degree of fibrosis,and decreased expression of caspase-1,GSDMD,NLRP3,COL-Ⅰ,COL-Ⅲ,and α-SMA proteins in lung tissue(P＜0.01).Conclusion RAS-RA has an inhibitory effect on radiation-in-duced pulmonary fibrosis,and its mechanism may be related to the inhibition of pyroptosis through the regu-lation of the NLRP3/caspase-1/GSDMD signaling pathway.

Angiography ; Cardiac Catheterization ; Child ; Child, Preschool ; Female ; Heart Septal Defects, Ventricular ; diagnosis ; surgery ; Humans ; Male ; Septal Occluder Device ; Treatment Outcome

BACKGROUNDCurrently, transcatheter closure of perimembranous ventricular septal defect (pmVSD) is a widely accepted therapeutic modality. However, arrhythmias, especially postprocedural heart blocks, are a concern and outcomes are not very clear. This study explored the outcomes and risk factors of arrhythmias associated with transcatheter device closure of pmVSD.

METHODSA total of 395 patients diagnosed with pmVSD who successfully underwent transcatheter intervention between January 2010 and December 2015 in our center were retrospectively reviewed. Electrocardiographic data before and after the procedure were collected and analyzed. We first evaluated the potential risk factors including gender, age, weight, inlet and outlet diameters of defect, subaortic rim length, occluder size, corrected occluder size into body surface area, fluoroscopy time, presence of aneurysm, and deployment position. We compared the potential risk factors between arrhythmia and nonarrhythmia groups using univariate analysis, followed by logistic analysis for independent risk factors.

RESULTSVarious arrhythmias were detected in 95 cases (24.1%) following transcatheter closure procedure. Logistic regression analysis revealed that eccentric (odds ratio [OR] 2.9, 95% confidence interval [CI]: 1.2-7.2) and large occluders (OR 2.0, 95% CI: 1.6-2.5), as well as long fluoroscopy time (OR 1.1, 95% CI: 1.1-1.2), were correlated with postprocedural arrhythmia. During 35.5 months (range: 9-80 months) of follow-up, most of the patients (74 out of 95) reverted to normal heart rhythm.

CONCLUSIONSThe mid-term outcome of patients with arrhythmias after transcatheter closure of pmVSD was satisfactory as most of the patients recovered normal rhythm. Eccentric, large device and long fluoroscopy time increase the risk of arrhythmias after transcatheter closure of pmVSD.

Arrhythmias, Cardiac ; diagnosis ; etiology ; Cardiac Catheterization ; adverse effects ; Cardiac Surgical Procedures ; adverse effects ; Child ; Child, Preschool ; Electrocardiography ; Female ; Heart Septal Defects, Ventricular ; physiopathology ; surgery ; Humans ; Male ; Retrospective Studies ; Risk Assessment ; Risk Factors ; Septal Occluder Device ; adverse effects ; Treatment Outcome

OBJECTIVE: To explore clinical effectiveness and safety of ultrasound-guided closed reduction and K-wires internal fixation in treating of Kilfoyle Ⅱand Ⅲ medial condylar fracture of humerus in children. METHODS: Clinical data of 32 children with medial condylar fracture of humerus treated with closed reduction and internal fixation with K-wires under the guidance of ultrasound were retrospectively analyzed from January 2014 to August 2019, including 23 males and 9 females, age ranged from 3.2 to 12.8 years old with an average of (8.3±2.1) years old;According to classification of Kilfoyle, 12 patients classified to typeⅡ and 20 patients were type Ⅲ;5 patients combined with elbow dislocation;the time from injury to operation ranged from 1 to 5 days with an average of (3.1±1.3) days. Radiological evaluation of treatment results and complications were observed. At the final follow up, Mayo elbow performance score(MEPS) was used to evaluate elbow function. And humerus-ulna angle on the affect side and healthy side were measured and compared. RESULTS: All patients were followed up from 8 to 26 months with an average of(19.3±5.5) months. All fractures were healed well, the healing time ranged from 4 to 6 weeks with an average of (4.5±0.5) weeks. No infection, vascular and nerve injury, bone nonunion, trochlear necrosis, cubitus varus or valgus deformity were occurred. According to Mayo scoring, all patients were assessed as excellent. There was no significant difference in angle of humerus-ulna between affectedside (9.5±3.6)° and healthy side (9.1±3.5)°, and no difference in MEPS scores between affected side(95.3±2.5) and healthy side(96.3±2.2)( CONCLUSION For Kilfoyle typeⅡand Ⅲ medial condylar fracture of humerus in children, closed reduction and internal fixation with K-wire under ultrasound guidance is a safe and effective method, and could promote in further.
Bone Wires ; Child ; Child, Preschool ; Female ; Fracture Fixation, Internal ; Humans ; Humeral Fractures/surgery* ; Humerus ; Male ; Retrospective Studies ; Treatment Outcome ; Ultrasonography, Interventional

Actinin/genetics* ; Anemia ; Blood Platelets/pathology* ; Female ; Humans ; Male ; Megakaryocytes ; Mutation, Missense ; Pedigree ; Thrombocytopenia/genetics*

【Objective】 To establish a blood transfusion outcome prediction model for comprehensivel evaluation of coagulation function of patients with upper gastrointestinal bleeding by thrombelastogram (TEG) and blood coagulation indicators. 【Methods】 The data of 101 patients with upper gastrointestinal hemorrhage, admitted to the Department of Gastroenterology of Zhejiang Provincial People′s Hospital and its Chun′an Branch from June 2018 to June 2021, were collected through Tongshuo blood transfusion management system and His system. Those patients were divided into blood transfusion group (n=56) and non-transfusion group (n=45), and into cirrhosis group (n=74) and non-cirrhosis group (n=27), and 40 patients, with non-upper gastrointestinal bleeding, were enrolled as the control. The results of TEG indicators (R, K, α, MA), coagulation function (PT, INR, APTT, TT, Fib), blood routine (Hb, Plt, WBC, NEUT%) and biochemical detection(Alb, SCr, ALT, AST, GGT) before transfusion were compared between groups and the correlation between TEG indicators and traditional coagulation parameters was analyzed. Single-factor and multi-factor analysis were used to screen blood transfusion-related factors to establish a predictive model. 【Results】 The comparisons of paremeters between transfusion and non-transfusion group were as follows, K (min), α (°), and MA (mm) was 3.86±3.12 vs 2.50±1.47, 54.00±14.08 vs 61.05±10.88, and 51.12±13.37 vs 58.26±11.08, respectively (P<0.01); PT (s) and Fib (g) was 16.36±7.45 vs 13.44±1.50 and 1.59±0.87 vs 2.35±1.09 (P<0.01); NEUT% and Hb (g/L) was 0.75 ±0.13 vs 0.66±0.15 and 68.04±14.49 vs 100.73±22.92 (P<0.01); Alb (g/L) and SCr (nmol/L) was 29.73±6.08 vs 33.73±7.19 and 99.50±53.55 vs 76.25±19.28 (P<0.01). Correlation analysis showed that APTT was positively correlated with R and K values, and negatively correlated with α and MA. Fib was negatively correlated with K values, and positively correlated with α and MA. Plt was negatively correlated with K values, and positively correlated with α and MA (P<0.01). Eight pre-transfusion indicators as K, MA, PT, Fib, NEUT%, Hb, Alb, and SCr were subjected to Logistic regression to establish a blood transfusion prediction model. The optimal ROC curve of blood transfusion threshold (blood transfusion predictive value of patients), sensitivity, specificity and AUC were 0.448, 92.9%, 88.9%, and 0.969, respectively. 【Conclusion】 The establishment of Logistic regression model by integrating detection indicators of TEG, coagulation function, blood routine and biochemistry in patients with upper gastrointestinal bleeding have showed significant correlation with blood transfusion prediction, and good clinical practicability.

OBJECTIVE: To observe and compare the therapeutic effects of hydroxypropyl chitosan ferrous ion complex solution and ferrous sulfate solution in iron deficiency anemia rats and their effects on gastric mucosa. METHODS: Seven rats were randomly selected from thirty five SPF grade SD rats as control group, and were fed with normal diet, distilled water (E). The rest of SD rats were fed with low iron feed and distilled water plus continuous tail vein bloodletting to establish the iron deficiency anemia model. After the model was established successfully, the rats were randomly divided into four groups: blank control group (A), iron deficiency anemia control group (B), ferrous sulfate group (C), hydroxypropyl chitosan ferrous ion complex (HPCTS-Fe RESULTS: After modeling, except the normal control group, the hair color of the rats in the four groups showed dark yellow and the belly of the toes became white gradually. HGB, HCT, Ret%, MCV, MCH, MCHC and SF decreased significantly (P < 0.05). After treatment, the rats with dark yellow hair in group C and D were improved, and the toe abdomen turned pink gradually. RBC, HGB, HCT, Ret%, MCV, MCH, MCHC and SF in rats in group C and D increased, which were higher than those in group B (P < 0.05). The HGB of the rats in group D was higher than that of group C in day 28th during treatment and the Ret% was higher than that in group C at day 10th (P<0.05).After treatment, the liver and spleen of the rats in group C and D were lighter than those in group B (P<0.05).The gastric mucosa in group A, B, D and E was not damaged obviously, while it was slightly irritated and damaged in group C. CONCLUSION Hydroxypropyl chitosan ferrous complex solution can improve the hemoglobin level of SD rats with iron deficiency anemia, which is stronger than ferrous sulfate solution and shows no damage to gastric mucosa.
Anemia, Iron-Deficiency/drug therapy* ; Animals ; Chitosan ; Ferrous Compounds ; Hemoglobins ; Iron ; Rats ; Rats, Sprague-Dawley

This study aimed to investigate the anti-fatigue effect and mechanism of Lubian(Cervi Penis et Testis) on kidney Yin deficiency and kidney Yang deficiency mice. After one week of adaptive feeding, 88 healthy male Kunming mice were randomly divided into a blank group, a kidney Yin deficiency model group, a kidney Yin deficiency-Panacis Quinquefolii Radix(PQR) group, kidney Yin deficiency-Lubian treatment groups, a kidney Yang deficiency model group, a kidney Yang deficiency-Ginseng Radix et Rhizoma(GR) group, and kidney Yang deficiency-Lubian treatment groups, with eight mice in each group. The kidney Yin deficiency model and kidney Yang deficiency model were prepared by daily regular oral administration of dexamethasone acetate and hydrocortisone, respectively, and meanwhile, corresponding drugs were provided. The mice in the blank group received blank reagent. The treatment lasted 14 days. The exhaustive swimming time was measured 30 min after drug administration on the 14th day. On the 15th day, blood was collected from eyeballs and the serum was separated to determine the content of lactic acid(LD), blood urea nitrogen(BUN), lactate dehydrogenase(LDH), cyclic adenosine monophosphate(cAMP), and cyclic guanosine monophosphate(cGMP). The liver was dissected to determine the content of liver glycogen and the protein expression of phosphoinositide 3-kinase(PI3K) and protein kinase B(Akt). Compared with the kidney Yang deficiency model group, the kidney Yang deficiency-Lubian treatment groups showed increased body weight(P<0.05), relieved symptoms of Yang deficiency, decreased cGMP content(P<0.01), increased cAMP/cGMP(P<0.01), prolonged exhausted swimming time(P<0.01), reduced LD(P<0.01), elevated BUN content(P<0.01), increased liver glycogen content(P<0.01), and increased protein expression of PI3K and Akt in the liver(P<0.05). Compared with the kidney Yin deficiency model group, the kidney Yin deficiency-Lubian treatment groups showed increased body weight(P<0.01), relieved symptoms of Yin deficiency, increased content of cGMP(P<0.01), decreased cAMP/cGMP(P<0.01), prolonged exhausted swimming time(P<0.01), decreased LD(P<0.01), decreased BUN content(P<0.01), increased liver glycogen content(P<0.01), and increased protein expression of PI3K(P<0.05) and Akt in the liver(P<0.05). To sum up, Lubian can regulate Yin deficiency and Yang deficiency and increase glycogen synthesis by affecting the PI3K-Akt pathway, thereby exerting an anti-fatigue role.
Male ; Mice ; Animals ; Phosphatidylinositol 3-Kinases/genetics* ; Proto-Oncogene Proteins c-akt/genetics* ; Liver Glycogen ; Yang Deficiency/drug therapy* ; Yin Deficiency/drug therapy* ; Kidney ; Body Weight

A case-control study was conducted to investigate associations between organophosphate pesticide (OP) exposure, aggression, impulsivity, and attempted suicide. Questionnaires were used to collect information; impulsivity and aggression were measured by the Barratt Impulsivity Scale (BIS) and the Aggression Inventory (AI). A greater number of OP symptoms was associated with an increased odds of a suicide attempt after adjusting for marital status and income (OR = 1.45; CI 1.14-1.86). Attempted suicide was significantly associated with high impulsivity scores (means: 72.4 vs. 60.6, P < 0.0001) and high aggression scores (means: 38.5 vs. 26.1, P < 0.0001). Suicide attempters had a higher number of OP exposure symptoms than controls and scored higher on scales of impulsivity and aggression.
Adult ; Aggression ; Case-Control Studies ; China ; epidemiology ; Female ; Humans ; Impulsive Behavior ; Male ; Middle Aged ; Occupational Exposure ; Organophosphate Poisoning ; complications ; Organophosphates ; adverse effects ; Pesticides ; adverse effects ; Risk Factors ; Suicide, Attempted ; statistics & numerical data

BACKGROUNDIdiopathic membranous nephropathy (IMN) is an autoimmune disease and the leading cause of adult nephritic syndrome. HLA-DQA1 had been identified to be associated with IMN in Europeans and the result was replicated in Chinese Han population. In this study, six single nucleotide polymorphisms (SNPs) in the promoter of HLA-DQA1 and other two SNPs with IgA nephropathy were included for the association analysis.

METHODSThe SNPs were genotyped in 509 patients and 601 controls by the MassArray iPLEX. The quantification of anti-phospholipase A2 receptor (PLA2R) antibodies in sera of IMN patients was performed by anti-PLA2R ELISA (IgG) kit.

RESULTSAfter analysis, four SNPs were significantly associated with IMN, with rs2187668 and rs28383345 as the top two signals (P = 8.42×10-5 and 2.48×10-5, respectively). Even under dominant model, the two SNPs were still significantly associated with IMN (P = 3.50×10-3 for rs28383345 and P = 6.55×10-5 for rs2187668). After conditional study with rs2187668, rs28383345 was the only variant significantly correlated with IMN after Bonferroni correction (P = 0.016). The minor alleles of the two SNPs were also mutually exclusive in our cohort. This indicated that the two SNPs were independently associated with IMN in Chinese Han population. Levels of anti-PLA2R autoantibodies were correlated with the genotypes of the two SNPs, but not significantly (P>0.05).

CONCLUSIONSOur results revealed that a novel independent variant in the promoter of HLA-DQA1 was associated with IMN in Chinese Han population. The locus possessed regulatory role according to the data of RegulomeDB. The exact role of the SNPs on the expression of HLA-DQA1 needs further investigation.