Objective:To study the role of cadherin 1 (CDH1) gene DNA methylation in autoimmune thyroiditis (AIT) in population from different water-iodine regions.Methods:From May to June 2019, the information of AIT cases and healthy individuals in Shandong Province were collected in three types of water-iodine regions: iodine-fortification (IF) region, iodine-adequate (IA) region and iodine-excess (IE) region. A case-control study design was applied to match 176 AIT cases (case group) with age, gender, body mass index, and place of residence in a 1 ∶ 1 ratio to 176 healthy individuals (control group). Fasting urine and whole blood samples were collected to test the contents of urinary iodine, thyroid function indicators [serum free triiodothyronine (FT 3), free thyroxine (FT 4), thyroid stimulating hormone (TSH)], and serum iodine. The DNA methylation levels of the target region of the CDH1 gene and its four CpG sites in whole blood were determined using methylation sequencing technology for target regions (MethylTarget TM). Results:The DNA methylation level of the target region of CDH1 gene in the case group was 0.832 ± 0.044, and that in the control group was 0.828 ± 0.049, there was no statistically significant difference between the two groups ( t = 0.76, P = 0.448). There was no statistically significant difference in DNA methylation levels of the four CpG sites in the target region of CDH1 gene between the case group and the control group ( P > 0.05). There was no statistically significant difference in the DNA methylation level of the CDH1 gene target region between the case group and the control group in IF, IA and IE regions ( P > 0.05). The detection results of DNA methylation levels at CpG sites in the target region of CDH1 gene in different water iodine regions showed that the DNA methylation level at site 83 in case group in IF region was higher than that in the control group ( t = 2.30, P = 0.023). However, there was no statistically significant difference in the DNA methylation levels of the four CpG sites between the case group and the control group in IA and IE regions ( P > 0.05). The DNA methylation level of CDH1 gene target region in AIT patients was not significantly correlated with urinary iodine, serum iodine, and serum FT 3, FT 4, and TSH contents ( P > 0.05), but was significantly negatively correlated with age ( r =-0.19, P = 0.014). Conclusions:The DNA methylation level at CpG site 83 of CDH1 gene in AIT patients in IF region is significantly higher than that in control population, indicating that DNA methylation at this locus may be involved in the occurrence and development of AIT after iodine fortification. The DNA methylation level of CDH1 gene is negatively correlated with age.

Objective:To study the role of cadherin 1 (CDH1) gene DNA methylation in autoimmune thyroiditis (AIT) in population from different water-iodine regions.Methods:From May to June 2019, the information of AIT cases and healthy individuals in Shandong Province were collected in three types of water-iodine regions: iodine-fortification (IF) region, iodine-adequate (IA) region and iodine-excess (IE) region. A case-control study design was applied to match 176 AIT cases (case group) with age, gender, body mass index, and place of residence in a 1 ∶ 1 ratio to 176 healthy individuals (control group). Fasting urine and whole blood samples were collected to test the contents of urinary iodine, thyroid function indicators [serum free triiodothyronine (FT 3), free thyroxine (FT 4), thyroid stimulating hormone (TSH)], and serum iodine. The DNA methylation levels of the target region of the CDH1 gene and its four CpG sites in whole blood were determined using methylation sequencing technology for target regions (MethylTarget TM). Results:The DNA methylation level of the target region of CDH1 gene in the case group was 0.832 ± 0.044, and that in the control group was 0.828 ± 0.049, there was no statistically significant difference between the two groups ( t = 0.76, P = 0.448). There was no statistically significant difference in DNA methylation levels of the four CpG sites in the target region of CDH1 gene between the case group and the control group ( P > 0.05). There was no statistically significant difference in the DNA methylation level of the CDH1 gene target region between the case group and the control group in IF, IA and IE regions ( P > 0.05). The detection results of DNA methylation levels at CpG sites in the target region of CDH1 gene in different water iodine regions showed that the DNA methylation level at site 83 in case group in IF region was higher than that in the control group ( t = 2.30, P = 0.023). However, there was no statistically significant difference in the DNA methylation levels of the four CpG sites between the case group and the control group in IA and IE regions ( P > 0.05). The DNA methylation level of CDH1 gene target region in AIT patients was not significantly correlated with urinary iodine, serum iodine, and serum FT 3, FT 4, and TSH contents ( P > 0.05), but was significantly negatively correlated with age ( r =-0.19, P = 0.014). Conclusions:The DNA methylation level at CpG site 83 of CDH1 gene in AIT patients in IF region is significantly higher than that in control population, indicating that DNA methylation at this locus may be involved in the occurrence and development of AIT after iodine fortification. The DNA methylation level of CDH1 gene is negatively correlated with age.

AIM:To compare the risk of hypergly-caemia with PCSK9 inhibitors versus statins,based on U.S.Food and Drug Administration Adverse Events Reporting System(FAERS).METHODS:The hyperglycaemia reports induced by"alirocumab","evolocumab","atorvastatin"and"rosuvastatin"were utilized as the first suspected drugs from the database of FAERS from 2016 to the third quarter of 2023.The report odd ratio(ROR)method was employed.RESULTS:Based on the FAERS database,the ROR(95％CI)for hyperglycaemia due to Ali-rocumab versus Atorvastatin and Rosuvastatin were 0.628(0.545,0.724)and 0.307(0.263,0.357),the ROR(95％CI)for hyperglycaemia due to Evoloc-umab were 0.817(0.750,0.889)and 0.399(0.361,0.441),all generated no adverse reaction signals.The ROR(95％CI)for hyperglycaemia due to Ali-rocumab and Evolocumab versus all other drugs in FAERS were 1.488(1.315,1.682)and 1.934(1.845,2.027),all generated adverse reaction signals,re-spectively.CONCLUSION:Based on the FAERS data-base,PCSK9 inhibitors have a lower risk of hyper-glycemia than statins and deserve clinical attention.

PURPOSE: The effect of air pollution-related particulate matter (PM) on epithelial barrier function and tight junction (TJ) expression in human nasal mucosa has not been studied to date. This study therefore aimed to assess the direct impact of PM with an aerodynamic diameter less than 2.5 μm (PM2.5) on the barrier function and TJ molecular expression of human nasal epithelial cells. METHODS: Air-liquid interface cultures were established with epithelial cells derived from noninflammatory nasal mucosal tissue collected from patients undergoing paranasal sinus surgery. Confluent cultures were exposed to 50 or 100 µg/mL PM2.5 for up to 72 hours, and assessed for 1) epithelial barrier integrity as measured by transepithelial resistance (TER) and permeability of fluorescein isothiocyanate (FITC) 4 kDa; 2) expression of TJs using real-time quantitative polymerase chain reaction and immunofluorescence staining, and 3) proinflammatory cytokines by luminometric bead array or enzyme-linked immunosorbent assay. RESULTS: Compared to control medium, 50 and/or 100 µg/mL PM2.5-treatment 1) significantly decreased TER and increased FITC permeability, which could not be restored by budesonide pretreatment; 2) significantly decreased the expression of claudin-1 messenger RNA, claudin-1, occludin and ZO-1 protein; and 3) significantly increased production of the cytokines interleukin-8, TIMP metallopeptidase inhibitor 1 and thymic stromal lymphopoietin. CONCLUSIONS: Exposure to PM2.5 may lead to loss of barrier function in human nasal epithelium through decreased expression of TJ proteins and increased release of proinflammatory cytokines. These results suggest an important mechanism of susceptibility to rhinitis and rhinosinusitis in highly PM2.5-polluted areas.
Asthma ; Budesonide ; Claudin-1 ; Cytokines ; Enzyme-Linked Immunosorbent Assay ; Epithelial Cells ; Fluorescein ; Fluorescein-5-isothiocyanate ; Fluorescent Antibody Technique ; Humans ; Interleukin-8 ; Mucous Membrane ; Nasal Mucosa ; Occludin ; Particulate Matter ; Permeability ; Polymerase Chain Reaction ; Rhinitis ; RNA, Messenger ; Tight Junctions

Objective To investigate the clinical efficacy of laparoscopic spleen-preserving distal pancreatectomy (Kimura method and Warshaw method) for benign lesions of pancreatic body and tail.Methods The retrospective cohort study was conducted.The clinicopathological data of 39 patients with benign lesions of pancreatic body and tail who underwent laparoscopic spleen-preserving distal pancreatectomy in the Second Affiliated Hospital of Nanchang University between March 2008 and January 2018 were collected.Of 39 patients,28 undergoing Kimura method (splenic artery and vein-preserving distal pancreatectomy) were allocated into the Kimura group,and 11 undergoing Warshaw method (cutting splenic vessels and preserving short gastric vessels)due to serious adhesion between pancreatic body and tail and splenic hilum were allocated into the Warshaw group.Observation indicators:(1) operation situations;(2) postoperative situations;(3) follow-up situations.Followup using outpatient examination and telephone interview was performed to detect blood glucose level and tumor recurrence of patients up to March 2018.Measurement data with normal distribution were represented as (x)±s and comparison between groups was analyzed using the t test.Measurement data with skewed distribution were described as M (range) and comparison between groups was done using nonparametric rank-sum test.Comparisons of count data were analyzed using chi-square test or Fisher exact probability.Results (1) Operation situations:39 patients received laparoscopic spleen-preserving distal pancreatectomy,operation time and volume of intraoperative blood loss of 39 patients were respectively (194 ±58)minutes and 100 mL (range,30-800 mL).The operation time and volume of intraoperative blood loss were respectively (197±56)minutes,100 mL (range,30-800 mL) in the Kimura group and (186±63)minutes,150 mL (range,30-450 mL) in the Warshaw group,with no statistically significant difference between groups (t =0.494,Z =-0.597,P＞ 0.05).(2) Postoperative situations:time to anal exsufflation and duration of hospital stay were respectively (2.6±0.8)days,(9.2±7.3)days in 39 patients and (2.4±0.6)days,(7.5±4.2)days in the Kimura group and (2.8±1.3)days,(13.5±11.1)days in the Warshaw group,with no statistically significant difference between groups (t=-0.720,-1.736,P＞0.05).Seven patients had postoperative complications.The incidence of complication was 2/28 in the Kimura group,1 patient with pancreatic leakage at 5 days postoperatively was cured by 15-day B ultrasound guided catheter drainage,and 1 who was diagnosed as pulmonary infection by chest CT examination at 5 days postoperatively was discharged from hospital after 8-day anti-infection and sputum-inductive treatments.The incidence of complication was 5/11 in the Warshaw group,3 patients with sustained fever at 5 and 7 days postoperatively who were diagnosed as grade 1 splenic infarction by epigastric enhanced CT examination were improved and discharged from hospital by antibiotic and low molecular weight heparin treatments,and then epigastric enhanced CT re-examination at 3 months postoperatively showed recovery of splenic perfusion;1 with pancreatic leakage at 7 days postoperatively was cured by 18-day conservative treatment;1 who was diagnosed as delayed gastric emptying by upper gastrointestinal contrast at 16 days postoperatively was improved and then discharged from hospital by 15-day placement of intestinal feeding tube and nutrition support therapy.There were statistically significant differences in the incidences of overall complication and splenic infarction between groups (x2 =5.485,4.878,P＜0.05) and no statistically significant difference in the incidence of other complications between groups (P＞0.05).(3) Follow-up situations:39 patients were followed up for 12 months (range,2-64 months).During the follow-up,six patients had normal blood glucose level,and all patients had good quality of life,without recurrence.Conclusions Laparoscopic spleen-preserving distal pancreatectomy for the benign lesions of pancreatic body and tail is satisfactory in short-and long-term curative effects.The incidences of complication and splenic infarction of Kimura method are lower than that of Warshaw method.

Objective To explore the clinical efficacy of laparoscopic left hemihepatectomy for the treatment of intrahepatic bile duct stones.Methods The clinical data of 30 patients with left intrahepatic bile duct stones who were admitted to the Second Affiliated Hospital of Nancbang University from June 2013 to June 2014 were retrospectively analyzed.All the patients underwent laparoscopic left hemihepatectomy by the Glisson intra-and extra-pedicles vascular inflow occlusion techniques together with the removal of choledocholithiasis and right bile duct stones,and T tube placement or laparoscopic primary suture of common bile duct were selected according to the condition of bile duct.All the 30 patients were readmitted to hospital and detected by color Doppler ultrasound (CDUS),computed tomography (CT) and T tube cholangiography at postoperative month 1,and then received CDUS reexamination every 3 months.CT and MRI reexaminations were applied to patients with complication of residual stones if necessary.All the patients were followed up till July 2014.Results All the 30 patients were treated by laparoscopic hepatectomy with left hemihepatic vascular inflow occlusion,including 5 with conversion to open surgery and 25 with successful operation.The Glisson extra-and intra-pedicel vascular inflow occlusion techniques were used in 11 and 14 patients,respectively.The operation time and volume of blood loss were (158 ± 85) minutes and (405 ± 215) mL.Two patients received intraoperative blood transfusion.There were no residual stones in the 8 patients with choledocholithiasis by intraoperative choledochoscope,and primary suture of bile duct and T tube placement were done in 5 and 3 patients,respectively.No patients died.After operation,there were 2 patients with bile leakage and 1 with pleural effusion,and they were cured though drainage.One patient with subphrenic effusion was cured by B ultrasound-guided puncture and drainage.One patient had bleeding with the volume of blood loss of 500 mL,and was cured by conservative treatment.The duration of hospital stay in all the patients was (8.5 ± 2.3)days.No bile leakage and abdomen infection were detected by outpatient examination.The time of followup was 1-12 months,without recurrence of stones.Conclusion Laparoscopic left hemihepatectomy for the treatment of left intrabepatic bile duct stones is safe and feasible with satisfactory outcome.

Objective To study the effect of BRMS1 on the invasion and metastasis of ovarian cancer cells. Methods BRMS1 small interfering RNA (BRMS1-siRNA) was transfected into human ovarian cancer cell-line OVCAR3 by liposome transfection method. The cells were divided into 3 groups: experimental group with BRMSl-siRNA, negative control group with siRNA that did not impact any gene, blank control group without any transfection. Changes of invasion and migration in the cells were per-formed using transwell invasion and migration assay. Results BRMS1 gene was silenced in OVCAR3 cell line successfully detecting by quantitative real-time RT-PCR and immunoblotting.In transwell invasion assay,the numbers of cells in lower chamber passing through the membrane in transfected group were more than negative control group and blank control group (190±8.5, 144±7.8 and 146±6.8 respectively) (t=8.747, t=8.869, P=0.000), while in transwell migration assay, the numbers of cells in lower chamber passing through the membrane in transfected group were more than negative control group and blank control group were (231 ±8.9, 177±9.7 and 182±7.9 respectively) (t=9.314, t=9.224, P=0.000), both with significant differences among the 3 groups. Conclusion BRMS1 gene could suppress the invasion and metastasis of ovarian cancer cells.

OBJECTIVE:To study the curative effect and mechanism of ulinastatin (UTI) administered by two different routes for severe acute pancreatitis (SAP). METHODS: 50 healthy male SD rats were randomly divided into 5 groups: sham operation (SO) group (fed with water ad libitum), SAP model group, positive control(nafamostat) group, ulinastatin peripheral venous perfusion group, and ulinastatin celiac arterial perfusion group. SAP model was established in the latter four groups, and then the rats were treated with corresponding drugs. 12h later, sample tissues were taken from pancreas and lungs for measurement of MPO level and histopathologic observation and the blood samples were collected for measurement of serum amylase, TNF-? and TXB2. RESULTS: Levels of amylase, TNF-?, TXB2, MPO and Hughes histopathologic scores of pancreas and lungs in all drug-treated groups were significantly lower than in SAP group (P