Background Recent advances in understanding the toxic effects of inorganic arsenic have revealed that arsenic exposure impacts multiple endocrine organs, thereby altering their functions. However, the mechanisms underlying arsenic-induced thyroid injury remain unclear. Objective To investigate the mechanisms by which sodium arsenite (NaAsO₂) affects the proliferation and apoptosis of normal thyroid cells (Nthy-ori3-1) through the estrogen receptor (ER)-phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) signaling pathway. Methods Nthy-ori3-1 cells were cultured in vitro and divided into the following groups: a control group (complete medium without drugs, 0 μmol·L⁻¹), and NaAsO₂-treated groups at 1, 2, and 4 μmol·L⁻¹. Additionally, 1 μmol·L⁻¹ of the ER inhibitor ICI182780 was used to intervene in the NaAsO₂ exposure groups, resulting in the following combinations: 1 μmol·L⁻¹ NaAsO₂ + ICI182780, 2 μmol·L⁻¹ NaAsO₂ + ICI182780, and 4 μmol·L⁻¹ NaAsO₂ + ICI182780. The median lethal concentration of NaAsO₂ was determined using cell viability assay. Cell viability was assessed at 24, 36, and 48 h using Cell Counting Kit-8 (CCK-8) assay. Colony formation ability was evaluated via plate cloning assay. Apoptosis was detected using Hoechst 33342 staining. Protein and mRNA expression levels of ERα, ERβ, c-MYC, Bax, Bcl-2, PI3K, p-PI3K, AKT, and p-AKT were measured using Western blot (WB) and real-time quantitative PCR (qRT-PCR), respectively. Results The median lethal concentration of NaAsO₂ was determined to be 4.034 μmol·L⁻¹. CCK-8 assay at 24, 36, and 48 h revealed that, compared with the control group, the 1, 2, and 4 μmol·L⁻¹ NaAsO₂ groups significantly inhibited Nthy-ori3-1 cell proliferation (P < 0.001). The plate cloning assays demonstrated a concentration-dependent reduction in colony formation ability (P < 0.001). Following the ICI182780 intervention, the cell viability and colony formation ability in the 1, 2, and 4 μmol·L⁻¹ NaAsO₂ groups were significantly restored compared with the corresponding NaAsO₂-only groups (P < 0.001, P < 0.01). The Hoechst 33342 staining indicated that compared with the control group, the nuclear staining intensity and apoptosis levels in the 1, 2, and 4 μmol·L⁻¹ NaAsO₂ groups increased in a concentration-dependent manner (P < 0.001). However, the ICI182780 intervention reduced the apoptosis levels in the NaAsO₂-treated groups compared with their NaAsO₂-only counterparts (P < 0.001). The WB analysis showed that, compared with the control group, the protein expression of ERα, ERβ, c-MYC, Bcl-2, p-PI3K, and p-AKT in the 1, 2, and 4 μmol·L⁻¹ NaAsO₂ groups decreased manner (P < 0.001, P < 0.01), while the Bax expression increased in a concentration-dependent (P < 0.001); the PI3K and AKT protein levels showed no significant differences (P > 0.05). In the ICI182780-treated NaAsO₂ groups, the ERα, ERβ, c-MYC, Bcl-2, p-PI3K, and p-AKT protein expression increased (P < 0.001, P < 0.01), the Bax expression decreased (P < 0.001), and the PI3K and AKT levels remained unchanged (P > 0.05) compared with the corresponding NaAsO₂-only groups. The mRNA expression patterns of ERα, ERβ, c-MYC, Bcl-2, and Bax were consistent with the WB results. Conclusion NaAsO₂ inhibits proliferation and promotes apoptosis in Nthy-ori3-1 cells in a dose-dependent manner. The underlying mechanism likely involves NaAsO₂-mediated suppression of the ER-PI3K/AKT signaling pathway, which subsequently regulates downstream proliferation- and apoptosis-related genes.

Tubular aggregates(TA)are ultrastructural abnormalities in muscle biopsies,which can be detected in muscle biopsy specimens from patients with a variety of hereditary and acquired disorders.A 34-year-old male patient diagnosed with systemic lupus erythematosus(SLE)presented with intermittent muscle weakness localized to the proximal extremities of both lower limbs during prolonged oral administration of methylprednisolone,hydroxychloroquine and tacrolimus.Laboratory findings indicated normal creatine kinase levels,and anti-U1-RNP/Sm antibodies were elevated up to 49.45 RU/mL.Electromyography revealed myogenic lesions in the left iliopsoas muscle and muscle pathology demonstrated TA within the muscle fibers.Genetic testing excluded the possibility of hereditary disorders with tubular aggregas.Combined with literature review,the etiology and clinical characteristics of TA were discussed to increase the understanding of the diagnosis of diseases with TA.This case report demonstrates that SLE patients can have fluctuating muscle weakness and TA in muscle pathology.The symptoms of SLE can be partially relieved by adjusting SLE medications.

Objective:To examine the effect of short-term regular aerobic exercise on physical fitness of children with pulmonary with atresia ventricular septal defect after radical biventricular treatment.Methods:This was a prospective self pre-and post-control observation study. The subjects performed regular aerobic exercise for 10 days according to the exercise prescription. Body composition measurement and cardiopulmonary exercise test[lung ventilation function, maximum oxygen uptake(VO 2max), maximum oxygen pulse(O 2/HR max), ventilation oxygen uptake efficiency(OUES), exercise load time], 6 min walking distance(6MWD), sports psychometric test, motor function screening test and fitness test, were collected. The changes of test parameters and scale scoring before and after exercise were analyzed and compared. Results:A total of 7 children with PA/VSD after biventricular surgery were enrolled. The age ranged 8.2-16.2 years old, and there were 2 males and 5 females. VO 2max[(1 196.71±395.31)ml/min vs.(1 297.43±425.73)ml/min, P=0.031], O 2/HRmax[(82.43±7.53)ml/beat vs.(91.57±6.95)ml/beat, P<0.001]increased after exercise. The exercise load time was significantly increased compared with that before intervention[(476.43±35.73)s vs.(531.43±45.76)s, P=0.002]. Resting heart rate before exercise( P=0.013) and peak respiration exchange ratio(PeakRER, P=0.021) were significantly lower. Body composition tests suggest weight, intracellular water, protein and muscle content of lower limb were higher( P<0.05). The motor function score was higher than before( P=0.015); the score of sports fear was lower than before( P=0.009). There was no significant difference in lung capacity and 6-minute walking distance before and after exercise( P>0.05). There were no cardiovascular events during the study period. Conclusion:Short-term regular aerobic exercise for children with PA/VSD after biventricular surgery can improve exercise tolerance, increase lower limb muscle content, improve exercise fear and exercise function, and has good safety and feasibility.

Background Arsenic can enter the hypothalamus to induce estrogen effect and interfere with the function of the neuroendocrine system. The thyroid endocrine system (hypothalamic-pituitary-thyroid axis) is one of the main endocrine systems, and the mechanism of arsenic-induced thyroid endocrine toxicity is still unclear. Objective To investigate the effects of different arsenic exposure levels on estradiol (E2), hypothalamic thyrotropin-releasing hormone (TRH), and their receptor (ERα, ERβ, and TRHR) mRNAs in rats and the possible hypothalamic toxic pathway and mechanism. Methods Seventy Wister rats were randomly divided a control group (sterile water); low-, medium-, and high-dose arsenic exposure groups [0.8, 4.0, and 20.0 mg·kg⁻¹ sodium arsenite (NaAsO₂)]; estrogen receptor inhibitor (ICI182780) intervention + low-, medium-, and high-dose arsenic exposure groups; with 10 animals in each group, half male and half female. Rats in the arsenic exposure groups were exposed to NaAsO₂ by drinking water for 19 weeks, and rats in the intervention groups were injected with 0.5 mg·kg⁻¹ ICI182780 via tail vein at week 9, 3 times a week. The levels of E2 and TRH in serum of rats were detected by ELISA. The expression levels of estrogen receptor α (ERα), estrogen receptor β (ERβ), and TRH receptor (TRHR) mRNAs in hypothalamus of rats were detected by real-time PCR (RT-PCR). Results (1) E2 and its receptor mRNA: Compared with the control group, the serum E2 level of female rats was increased in the low-dose and the medium-dose arsenic exposure groups (P<0.05), and the serum E2 level of male rats was increased in the low-dose, the medium-dose, and the high-dose arsenic exposure groups (P<0.05), and the change of female E2 was greater than that of male rats. Compared with the control group, the relative expression levels of ERα mRNA and ERβ mRNA in female rats were increased in the low-dose, the medium-dose, and the high-dose arsenic exposure groups (P<0.05), so were the relative expression levels of ERα mRNA in male rats (P<0.05). (2) TRH and its receptor mRNA: Compared with the control group, the serum TRH level of female rats was increased in the high-dose arsenic group (P<0.05), the relative expression level of TRHR mRNA was increased in the low-dose, the medium-dose, and the high-dose arsenic exposure groups (P<0.05). Results (1) and results (2) suggested that females were more likely than males to have abnormal changes in E2, TRH, and related receptor genes after arsenic exposure. (3) Compared with female rats in the medium-high dose arsenic exposure group, the expressions of TRH and TRHR induced by arsenic exposure were inhibited after the intervention of ICI182780 (P<0.05), suggesting that arsenic in the hypothalamus may have toxic effects on TRH and TRHR by inducing estrogen-like effects. Conclusion Arsenic exposure can induce estrogen-like effects in the hypothalamus, interfere with thyroid function, and show dose-dependent and sex differences. E2 and TRH and their receptors may be the toxic pathway of arsenic-related estrogen-like effect.

Objective To analyze the clinical characteristics of IgG4-related disease (IgG4-RD)so as to improve the understanding of IgG4-RD in China.Methods IgG4-RD patients were recruited from Peking Union Medical College Hospital between January 2011 and January 2016.All patients were followedup for more than 6 months.The demographic characteristics,symptoms,organ involvements,laboratory examinations and treatment efficacy were evaluated and analyzed.Results A total of 346 patients were finally enrolled,including 230 males (66.5％) and 116 females (33.5％).The mean age of disease onset was (53.8 ± 14.2) years old.The mostly common involved organs were lymph nodes (56.4％) and submandibular glands (52.6％).Other affected organs and manifestations included:swelling of the lacrimal glands (46.5％),autoimmune pancreatitis (38.4％),pulmonary involvement (28.0％),sclerosing cholangitis (25.4％),naso-sinusitis (23.4％),parotid gland swelling (21.7％),retroperitoneal fibrosis (19.9％),large arteries involvement (9.5％),kidney involvement (obstructive nephropathy caused by retroperitoneal fibrosis was excluded) (6.9％),skin lesions (6.4％).Rare features consisted of thyroid glands,pituitary glands,gastrointestinal tract,pachymeningitis,pericardium,sclerosing mediastinitis and orchitis.The majority of patients had multi-organ involvement,such as 74.3％ patients with 3 and more,18.2％ and 7.5％ patients with 2 and single organ involvement respectively.The average IgG4-RD responder index (IgG4-RD RI) was 13.21 ±5.70.History of allergy was found in 172 (49.7％) patients.As to the laboratory tests,elevated serum IgG4 levels were confirmed in 285 (94.1％) patients,which was positively correlated with IgG4-RD RI.There were 33.5％ patients receiving monotherapy of glucocorticoid,52.6％ treated with glucocorticoids combined with immunosuppressive agents,4.9％ patients with immunosuppressant only,and 9.0％ patients with mild disease not receiving medication.The majority (336,97.1％) patients improved the above regimens.Conclusion IgG4-RD is a systemic fibro-inflammatory disease with multiple organ involvement.The mostly common involved organs include lymph node,submandibular glands,and pancreas.Glucocorticoids and immunosuppressive agents were effective for IgG4-RD.

Objective To investigate the development and influence factors of collateral circulation between spleen and lung in patients with portal hypertension after modified splenopneumopexy.Methods Data of 59 patients from January 2009 to December 2014 were analyzed,and the development of collateral circulation between spleen and lung after surgery were evaluated with ultrasound.Patients were divided into obvious collaterals group (maximum collateral diameter ≥ 2 mm,n =43) and non-obvious collaterals group (maximum collateral diameter ＜ 2 mm,n =16) according to ultrasound examination 3 months after surgery.Gender,age,type of disease,Child-Pugh classification,free portal pressure,portal vein diameter,splenic vein diameter,splenic artery diameter,splenic length,ejection fraction,forced vital capacity rate of one second (FEV1％),whether partial splenectomy was performed,and management of splenic upper pole were recorded and analyzed between the two groups.Results 3 months after surgery obvious collateral circulation could be observed in 43 patients,6 months after surgery the number increased to 53 (x2 =4.526,P ＜ 0.05).Splenic length (t =2.092) and FEV1％ (t =2.233) were significantly higher in obvious collaterals group (all P ＜ 0.05),and there were no statistical differences in gender (x2 =0.092),age (t =-1.254),type of disease (x2 =1.565),Child-Pugh classification (Z =-1.821),free portal pressur (t =0.912),portal vein diameter (t =0.008),splenic vein diameter (t =-0.485),splenic artery diameter (t =0.397),ejection fraction (t =-0.852),whether partial splenectomy was performed (x2 =0.002),and management of splenic upper pole (x2 =1.731) between the two groups (all P ＞ 0.05).Conclusions Obvious collateral circulation can develop between spleen and lung in patients with portal hypertension after modified splenopneumopexy,and the development of collateral circulation is associated with splenic length and FEV1％.

Objective To investigate the risk factorsthat predict pain during colonoscopy for decision of sedation or analgesia before the examination. Methods A total of 283 consecutive patients undergoing colonoscopicexamination at Nanfang Hospital between July, 2016 and September, 2016were retrospectively analyzed. The clinical data and visual analogue scale after the examination were analyzed to identify the risk factors for pain during colonoscopy using univariate analysis and multivariate logistic regression. A risk stratification model for predicting pain in colonoscopy was established. Results The completion rate of the procedure was significantly lower in patients with a visual analogue scale ≥5 (P<0.000). Univariate analysis showed that female patients, previous abdominal surgery, no previous experience with colonoscopy, complaint of abdominal pain before colonoscopy, insufficient experience of the endoscopists, patient's anticipation of high painlevelbefore examination, and a low body mass index (BMI) were all associated with the experience of pain in colonoscopy (P<0.05). Multivariate logistic regressionanalysis identified BMI index (X1), level of experience of the endoscopist (A1, A2, A3) and the patient's anticipation of painlevel (X2) as the risk factors of pain in colonoscopy(P<0.05), and the establishedmodel with the 3 variables was:P=eY/(1+eY),Y=0.049-0.124 × X1-0.97 × X2+1.713 × A1+0.781 × A2+0.147 × A3, which showed a sensitivity of 70.3%and a specificity of 67.5%for predicting pain in colonoscopy. Conclusion The patient's anticipation of a high pain level in colonoscopy, insufficient experience of the endoscopist, and a low BMI are the independent risk factors for pain in colonoscopy, and evaluation of these factors can help in the decision-making concerning the use of sedation or analgesia before colonoscopy.

Objective To investigate the risk factorsthat predict pain during colonoscopy for decision of sedation or analgesia before the examination. Methods A total of 283 consecutive patients undergoing colonoscopicexamination at Nanfang Hospital between July, 2016 and September, 2016were retrospectively analyzed. The clinical data and visual analogue scale after the examination were analyzed to identify the risk factors for pain during colonoscopy using univariate analysis and multivariate logistic regression. A risk stratification model for predicting pain in colonoscopy was established. Results The completion rate of the procedure was significantly lower in patients with a visual analogue scale ≥5 (P<0.000). Univariate analysis showed that female patients, previous abdominal surgery, no previous experience with colonoscopy, complaint of abdominal pain before colonoscopy, insufficient experience of the endoscopists, patient's anticipation of high painlevelbefore examination, and a low body mass index (BMI) were all associated with the experience of pain in colonoscopy (P<0.05). Multivariate logistic regressionanalysis identified BMI index (X1), level of experience of the endoscopist (A1, A2, A3) and the patient's anticipation of painlevel (X2) as the risk factors of pain in colonoscopy(P<0.05), and the establishedmodel with the 3 variables was:P=eY/(1+eY),Y=0.049-0.124 × X1-0.97 × X2+1.713 × A1+0.781 × A2+0.147 × A3, which showed a sensitivity of 70.3%and a specificity of 67.5%for predicting pain in colonoscopy. Conclusion The patient's anticipation of a high pain level in colonoscopy, insufficient experience of the endoscopist, and a low BMI are the independent risk factors for pain in colonoscopy, and evaluation of these factors can help in the decision-making concerning the use of sedation or analgesia before colonoscopy.

Background and objective Surgical procedure is the main method of treating lung cancer.Meanwhile,postoperative pneumonia (POP) is the major cause of perioperative mortality in lung cancer surgery.The preoperative pathogenic airway bacterial colonization is an independent risk factor causing postoperative pulmonary complications (PPC).This cross-sectional study aimed to explore the relationship between preoperative pathogenic airway bacterial colonization and POP in lung cancer and to identify the high-risk factors of preoperative pathogenic airway bacterial colonization.Methods A total of 125 patients with non-small cell lung cancer (NSCLC) underwent thoracic surgery in six hospitals of Chengdu between May 2015 and January 2016.Preoperative pathogenic airway bacterial colonization was detected in all patients via fiber bronchoscopy.Patients' PPC,high-risk factors,clinical characteristics,and the serum surfactant protein D (SP-D) level were also analyzed.Results The incidence of preoperative pathogenic airway bacterial colonization among NSCLC patients was 15.2％ (19/125).Up to 22 strains were identified in the colonization positive group,with Gram-negative bacteria being dominant (86.36％,19/22).High-risk factors of pathogenic airway bacterial colonization were age (≥75 yr) and smoking index (≥≥400 cigarettes/year).PPC incidence was significantly higher in the colonization-positive group (42.11％,8/19) than that in the colonization-negative group (16.04％,17/106)(P=0.021).POP incidence was significantly higher in the colonization-positive group (26.32％,5/19) than that in the colonization-negative group (6.60％,7/106)(P=0.019).The serum SP-D level of patients in the colonization-positive group was remarkably higher than that in the colonization-negative group [(31.25±6.09)vs (28.17±5.23)] (P=0.023).The incidence of preoperative pathogenic airway bacterial colonization among NSCLC patients with POP was 41.67％ (5/12).Ihis value was 3.4 times higher than that among the patients without POP (OR=3.363,95％CI:1.467-7.711).Conclusion An intimate correlation was observed between POP and pathogenic airway bacterial colonization in lung cancer.The high-risk factors of pathogenic airway bacterial colonization were age and smoking index.

Objective To investigate the risk factors of multiple recurrent bile duct stones in patients with common bile duct (CBD) stones and received endoscopic sphincterotomy (EST ) treatment . Methods From June 1st ,2007 to June 1st ,2011 ,the patients received EST treatment were followed up , the follow‐up time was three to seven years .A total of 2 738 patients were successfully followed up , including 24 patients with two or more than two times of recurrent bile stone after EST who were enrolled in multiple recurrence group .One hundred patients without recurrence were randomly selected by table of random number as control group .The clinical data of two groups were compared by t test or Chi‐square test .The factors were analyzed with multivariate Logistic regression analysis and try to find out the risk factors of multiple recurrence .Results The comparative analysis between two groups showed that the three factors of juxtapapillary duodenal diverticula [17 .0% (17/100 ) vs 41 .7% (10/24 )] ,history of biliary tract surgery [13 .0% (13/100) vs 45 .8% (11/24)] and the angle enclosed between the horizontal portion of the CBD and the horizontal plane (angleofbile duct) less than 45° [2 .0% (2/100) vs 20 .8% (5/24)] were statistically significant (χ2 = 6 .914 、13 .37 、9 .595 ,all P < 0 .01 ) . Furthermore , logistic regression analysis indicated that juxtapapillary duodenal diverticula (B = 1 .421 ,OR = 4 .142 ,P = 0 .01) , history of biliary tract surgery (B = 1 .612 ,OR = 5 .011 ,P= 0 .004) and the angle of bile ductless than 45° (B= 2 .661 ,OR= 14 .31 ,P= 0 .005) were risk factors of multiple recurrence .Conclusion Juxtapapillary duodenal diverticula , history of biliary tract surgery , and the angle of bile duct less than 45° are independent risk factors of multiple recurrence of CBD stones .