Objective To explore the effect of dronedaronel on hyperpolarization-activated cyclic-nucleotide-gated(HCN) channel expression by detecting the change of HCN channel mRNA and protein level before and after giving dronedarone in neonatal rat ventricular myocytes.Methods Neonatal rat ventricular myocytes were separated and digested by type Ⅱ collagenase,and then single ventricular myocytes were collected through differential sticking wall separation method.According to the concentrations (0.1,0.5,1.0,5.0,10.0,20.0 μmol/L of dronedaronel for treating myocytes for 48 h) and time(10 μmol/L of dronedaronel for treating myocytes for 1,6,12,24,48 h)the gradient grouping was conducted.The levels of HCN2 and HCN4 channel mRNA and protein level were determined by real-time PCR and Western blot.Results The HCN2 mRNA and HCN4 mRNA expression levels in concentration gradient group and time gradient group were lower than those in the control group(P＜0.05);compared with the control group,the protein level in the 10 umol/L dronedaronel treatment for 12 h group was significantly down-regulated(P＜ 0.01).Conclusion Dronedaronel could inhibit the expression of HCN2/HCN4 channel mRNA and protein,moreover its action shows the concentration dependency and reaches the maximum at 12 h after medication.

Objective To explore the clinicopathological features and prognostic significance of human epidermal growth factor receptor 2 (HER2) in gastric carcinoma. Methods Pathological data of 127 patients with gastric carcinoma were retrospectively analyzed. HER2 expressions of all patients were detected by immunohistochemistry (IHC). 119 (93.7 %) patients were undergone R0 dissection and 123 (96.9 %) cases received D2 lymph nodes dissection. 51 (40.2 %) patients received adjuvant chemotherapy. The proportional differences of clinicopathological features for patients between HER2-positive and HER2-negative were compared, including the patients' survival. Results HER2 overexpression rate was 8.7 % (11/127) in gastric carcinoma patients. For the patients with HER2-positive and HER-negative, the lymph node metastasis rates were 100.0 % (11/11) and 81.9 % (95/116), respectively (P= 0.041). The 3-year overall survival (OS) rates for HER2-positive and HER2- negative patients with gastric carcinoma were 32.7 % and 42.9 % (P=0.413), and the 5-year progression free survival (PFS) rates were 27.3 % and 42.2 % (P = 0.354), respectively. Among patients with HER2-negative, 3-year OS rate for patients with surgery plus adjuvant chemotherapy was 55.3%, compared with 35.4%for patients with surgery alone (P=0.015), and the 3-year PFS rates were 53.3 % and 35.3 % (P= 0.038), respectively. Among patients with HER2-positive patients, 3-year OS rate for patients with surgery plus adjuvant chemotherapy was 0, compared with 75.0%for patients with surgery alone (P=0.002), and the 3-year PFS rates were 0 and 60.0% (P=0.004). Conclusions HER2 is expressed in gastric carcinoma tissue, related to lymph node metastasis. HER2 status are not correlated with the prognosis for gastric carcinoma patients, however, it is likely to be a predictive marker for adjuvant treatment after surgery for patients with gastric carcinoma.

Objective To observe the clinical characteristics ofretinoblastoma (RB) in Southwest China.Methods A retrospective clinical study.From January 2010 to December 2017,66 RB patients diagnosed in Ophthalmology Department of West China Hospital of Sichuan University were included in the study.All the patients underwent ocular B-ultrasound,orbital CT or MRI examination.Ten patients underwent RetCam examination at the same time.Twenty-nine patients were diagnosed by histopathological examination,and 37 patients were diagnosed by clinical symptoms and imaging examination.According to whether the tumor invaded the orbit and optic nerve,it could be divided into extraocular stage and intraocular stage.Intraocular tumors were divided into A-E stages according to the international intraocular RB classification.Treatments were performed according to different stages.The general information,age at diagnosis,course of diseases (the time between onset symptoms and diagnosis),causes of visiting a doctor,classification,treatment methods and eyeball preservation rate were retrospectively analyzed.Results Patients all came from Southwest China (56 patients from Sichuan Province,2 patients from Yunnan Province,2 patients from Guizhou Province,and 6 patients from Tibet).The permanent residence were identified in 43 patients,including 27 patients (62.8％) from rural areas.There were 38 males (57.6％);50 unilateral tumors (75.8％) and 16 bilateral tumors (24.2％);51 firstvisiting patients (77.3％) and 15 re-visiting patients (22.7％).The average diagnostic age of first-visiting patients was 20.9 ± 14.4 months,with 23.2 ± 14.7 and 11.2 ± 7.6 months for unilateral and bilateral tumors,respectively.There were 41 patients had definite course and causes,of whom the average course was 90.6± 115.2 days.The most common cause was leucocoria in 32 patients (62.7％),followed by redness and swelling in 4 patients (9.8％),and other causes in 5 patients (12.2％).Among the 15 re-visiting patients,the average diagnostic age was 63.6± 46.8 months,the average course was 32.8 ± 45.5 months.Recurrence was occurred in 5 patients (33.3％),leucocoria in 4 patients (26.7％),postoperative complication in 3 patients (20.0％),protrusion in 2 patients (13.3％) and redness in 1 (6.7％) patient,respectively.Fifty out of 82 eyes were admitted to hospital,including 37 eyes of first-visiting patients and 13 eyes of re-visiting patients.Among 37 first-visiting eyes,there were 5 eyes (13.5％) in stage A-C,26 eyes (70.3％) in stage D-E,6 eyes (16.2％) in extraocular stage.Five eyes in stage A-C were treated with laser photocoagulation and (or) cryotherapy combined with systemic chemotherapy.Four eyes in stage D were treated with intraocular arterial chemotherapy.Nineteen eyes (51.3％) were performed with enucleation,2 eyes (5.4％) with evisceration and 7 eyes (18.9％) abandoned treatment.Among 13 re-visiting eyes,6 eyes (46.2％,with 5 eyes of recurrence) had been enucleated before,4 eyes (30.8％) were in extraocular stage and 3 eyes (23.1％) in stage D-E.Five eyes (38.5％) were treated with evisceration,4 eyes (30.8％) with enucleation,1 eye with oculoplastic surgery and 3 eyes (23.1％) abandoned treatment.The rate of eye preservation was 18.0％,29.0％ for intraocular stage and 0％ for extraocular stage,respectively.Conclusion RB patients in Southwest China have a longer course between onset symptoms and diagnosis,more advanced classification and lower rate of eye preservation.

Objective:To investigate the application of transverse closure of longitudinal incisions in repairing pentagonal full-thickness defects of the lower eyelid margin.Methods:A retrospective analysis was performed on clinical data collected from 26 patients with melanocytic nevi at the lower eyelid margin in Department of Dermatology, The Third People′s Hospital of Hangzhou from July 2016 to June 2019. Among the 26 patients, 10 were males, and 16 were females. After lesion resection, all the pentagonal full-thickness defects of the lower eyelid margin were repaired via transverse closure of longitudinal incisions.Results:All the pentagonal defects of the 26 cases were successfully repaired. The longitudinal incisions perpendicular to the eyelid were successfully converted into transverse incisions parallel to the eyelid margin and near the eyelash, and all incisions healed primarily. After surgery, mild congestion of the lower eyelid occurred in 3 patients, and temporary blurred vision in 1. During 1 - 2 years of postoperative follow-up, 26 patients all achieved symmetrical appearance of the skin and soft tissues around the eyes, without obvious postoperative scars or lower eyelid ectropion.Conclusions:Horizontal closure of longitudinal incisions can be used to repair the pentagonal full-thickness defects of the lower eyelid margin, because it can convert the incision closure line perpendicular to the lower eyelid margin into a horizontal transverse incision closure line parallel to the lower eyelid margin, so that the incisions and scars of the lower eyelid can be hided with a satisfactory cosmetic effect.

The in vitro release is an important index to evaluate the quality of liposome formulation.Currently, there is no evaluation method for the in vitro release of liposome in pharmacopoeia of various countries, which leads to the lack of unified standard and safety guarantee for the quality evaluation of liposome formulation.Taking the self-made paclitaxel derivative liposomes as an example, the paddle membrane binding method established by optimizing external release conditions was used to simulate the complete release of paclitaxel derivative drugs in 12 hours under physiological conditions.The results showed that using 0.5% SDS-HEPES as the release medium and a dialysis bag with a molecular weight cutoff of 1 000 kD to release the liposome solution met the requirements and had discrimination ability, providing a reference for the development of drug-loaded liposomes release methods in vitro.

Chronic obstructive pulmonary disease (COPD) refers to a common complex disease characterized by progressive and incomplete reversible airflow limitation.COPD is one of the leading causes on morbidity and mortality in China.Genetic risk factors play important roles on the occurrence of COPD.However,the genetic risk factors of COPD remain unknown,to some extent.The aim of this review is to provide a comprehensive overview on literature concerning the most promising findings related to genetic risk factors of COPD.

Objective:To summarize and analyze the efficacy of the upper eyelid orbicularis oculi myocutaneous island flap in repairing secondary defects after resection of eyelid and periorbital skin tumors.Methods:A retrospective analysis was carried out on clinical data collected from 28 patients, whose secondary eyelid and periorbital defects were repaired with the upper eyelid orbicularis oculi myocutaneous island flaps in the Department of Dermatology, Hangzhou Third People′s Hospital from August 2019 to June 2021. The survival condition of the flaps was observed after the operation, and the appearance of the upper eyelid and periorbital skin as well as tumor recurrence were evaluated during the follow up.Results:Among the 28 cases, there were 6 males and 22 females; their ages ranged from 47 to 87 years (70.5 ± 10.9 years), 7 patients were aged 80 - 89 years, 8 aged 70 - 79 years, 8 aged 60 - 69 years, 4 aged 50 - 59 years, and 1 patient was aged 40 - 49 years. Skin defects were distributed at the upper eyelid in 1 case, at the lower eyelid in 9 cases, at the inner canthus in 1 case, at the outer canthus in 3 cases, at the upper eyebrow in 1 case, at the dorsum of the nose in 3 cases, and at the junction of the external nose, inner canthus and lower eyelid in 10 cases. The skin defects varied from 1.0 cm × 0.5 cm to 3.1 cm × 2.3 cm in size. The designed upper eyelid orbicularis oculi myocutaneous flap was 0.5 - 1.8 cm in width and 3 - 4 cm in length, and the length of the subcutaneous tunnel was 1.2 - 2.5 cm. During the follow-up of 6 months to 1.5 years, all flaps survived; scars on the upper eyelid donor sites were not obvious; there was no upper eyelid ectropion, no trichiasis, and no eyelid closure abnormality after the operation.Conclusion:The medium- or small-sized defects of the eyelid and periorbital skin can be successfully repaired by the upper eyelid orbicularis oculi myocutaneous island flap, with a favorable cosmetic effect and concealed donor areas.

Objective:To investigate the clinical efficacy of bilateral V-Y advancement island flaps on buttocks in repairing postoperative defects in patients with perianal Paget′s disease.Methods:From January 2009 to January 2021, a retrospective analysis was performed on clinical data collected from 13 patients with perianal Paget′s disease, whose perianal defects resulting from the tumor resection were reconstructed with bilateral V-Y advancement island flaps on the buttocks in the Department of Dermatology, Hangzhou Third People′s Hospital. The postoperative recovery of the buttocks and the effects on the defecation function were evaluated.Results:The areas of perianal defects in 13 cases ranged from 4.8 cm × 5.6 cm to 12.2 cm × 6.4 cm. All defects were successfully repaired by using the bilateral V-Y advancement island flaps, and all surgical wounds healed primarily. One case first received temporary ileostomy, and then received ileostomy closure 3 months later, resulting in the recovery of defecation function; in another 1 case of perianal Paget′s disease comorbid with rectal cancer, the permanent sigmoid colostomy was performed to divert feces, and the defecation function was lost. After the follow-up for 1 - 6 years, the buttocks were symmetrical in shape in all the 13 patients, and 12 with preserved anus had normal defecation function. No tumor recurrence was observed in 12 patients without other malignant tumors after the operation, while 3 patients experienced mild anal stenosis without anal mucosa eversion or wound dehiscence; 1 patient with perianal Paget′s disease complicated by anal canal adenocarcinoma developed bilateral inguinal lymph node and internal iliac lymph node metastasis 1 year after the operation, and died 6 months later.Conclusion:The bilateral V-Y advancement island flaps on the buttocks have the advantages of reliable blood supply and sufficient advancement mobility, and can be used to repair large skin defects around the anus.

Objective:To explore the effects of short-term particulate matter(PM)exposure and the melatonin receptor 1B(MTNR1B)gene on triglyceride-glucose(TyG)index utilizing data from Fang-shan Family-based Ischemic Stroke Study in China(FISSIC).Methods:Probands and their relatives from 9 rural areas in Fangshan District,Beijing,were included in the study.PM data were obtained from fixed monitoring stations of the National Air Pollution Monitoring System.TyG index was calculated by fasting triglyceride and glucose concentrations.The associations of short-term PM exposure and rs10830963 polymorphism of the MTNR1B gene with the TyG index were assessed using mixed linear models,in which covariates such as age,sex,and lifestyles were adjusted for.Gene-environment inter-action analysis was furtherly performed using the maximum likelihood methods to explore the potential effect modifier role of rs10830963 polymorphism in the association of PM with TyG index.Results:A total of 4 395 participants from 2 084 families were included in the study,and the mean age of the study participants was(58.98±8.68)years,with 53.90％females.The results of association analyses showed that for every 10 μg/m3 increase in PM2.5 concentration,TyG index increased by 0.017(95％CI:0.007-0.027),while for per 10 μg/m3 increment in PM1o,TyG index increased by 0.010(95％CI:0.003-0.017).And the associations all had lagged effects.In addition,there was a positive association between the rs10830963 polymorphism and the TyG index.For per increase in risk allele G,TyG index was elevated by 0.040(95％CI:0.004-0.076).The TyG index was 0.079(95％CI:0.005-0.152)higher in carriers of the GG genotype compared with carriers of the CC genotype.The inter-action of rs10830963 polymorphism with PM exposure had not been found to be statistically significant in the present study.Conclusion:Short-term exposure to PM2.5 and PM10 were associated with higher TyG index.The G allele of rs10830963 polymorphism in the MTNR1B gene was associated with the elevated TyG index.

Objective:To delve into the intricate relationship between common genetic variations across the entire genome and the risk of non-syndromic cleft lip with or without cleft palate(NSCL/P).Methods:Utilizing summary statistics data from genome-wide association studies(GW AS),a thorough investigation to evaluate the impact of common variations on the genome were undertook.This involved assessing single nucleotide polymorphism(SNP)heritability across the entire genome,as well as within specific genomic regions.To ensure the robustness of our analysis,stringent quality control measures were applied to the GWAS summary statistics data.Criteria for inclusion encompassed the absence of missing values,a minor allele frequency≥1％,P-values falling within the range of 0 to 1,and clear SNP strand orientation.SNP meeting these stringent criteria were then meticulously included in our analy-sis.The SNP heritability of NSCL/P was calculated using linkage disequilibrium score regression.Addi-tionally,hierarchical linkage disequilibrium score regression to partition SNP heritability within coding re-gions,promoters,introns,enhancers,and super enhancers were employed,and the enrichment levels within different genomic regions using LDSC(v1.0.1)software were further elucidated.Results:Our study drew upon GWAS summary statistics data obtained from 806 NSCL/P trios,comprising a total of 2 418 individuals from the Chinese population.Following rigorous quality control procedures,490 593 out of 492 993 SNP were deemed suitable for inclusion in SNP heritability calculations.The observed SNP heritability of NSCL/P was 0.55(95％CI:0.28-0.82).Adjusting for the elevated disease pre-valence within our sample,the SNP heritability scaled down to 0.37(95％CI:0.19-0.55)based on the prevalence observed in the general Chinese population.Notably,our enrichment analysis unveiled significant enrichment of SNP heritability within enhancer regions(15.70,P=0.04)and super enhan-cer regions(3.18,P=0.03).Conclusion:Our study sheds light on the intricate interplay between common genetic variations and the risk of NSCL/P in the Chinese population.By elucidating the SNP heritability landscape across different genomic regions,we contribute valuable insights into the genetic basis of NSCL/P.The significant enrichment of SNP heritability within enhancer and super enhancer re-gions underscores the potential role of these regulatory elements in shaping the genetic susceptibility to NSCL/P.This paves the way for further research aimed at uncovering novel genetic pathogenic factors un-derlying NSCL/P pathogenesis.