Dry eye disease (DED) is a prevalent and intractable ocular disease induced by a variety of causes. Elevated sphingomyelin (SM) levels and pro-inflammatory cytokines were detected on the ocular surface of DED patients, particularly in the meibomian glands. Sphingomyelin synthase 2 (SMS2), one of the proteins involved in SM synthesis, would light a novel way of developing a DED therapy strategy. Herein, we report the design and optimization of a series of novel thiophene carboxamide derivatives to afford 14l with an improved highly potent inhibitory activity on SM synthesis (IC_{50, SMS2} = 28 nmol/L). Moreover, 14l exhibited a notable protective effect of anti-inflammation and anti-apoptosis on human corneal epithelial cells (HCEC) under TNF-α-hyperosmotic stress conditions in vitro, with an acceptable ocular specific distribution (corneas and meibomian glands) and pharmacokinetics (PK) profiles (t _{1/2, cornea} = 1.11 h; t _{1/2, meibomian glands} = 4.32 h) in rats. Furthermore, 14l alleviated the dry eye symptoms including corneal fluorescein staining scores and tear secretion in a dose-dependent manner in mice. Mechanically, 14l reduced the mRNA expression of Tnf-α, Il-1β and Mmp-9 in corneas, as well as the proportion of very long chain SM in meibomian glands. Our findings provide a new strategy for DED therapy based on selective SMS2 inhibitors.

Objective:To evaluate the long-term impact of three different outdoor activity intervention strategies on the prevalence of myopia among school-aged children in China.Methods:Cross-sectional data from the Refractive Error Study in Children (RESC) on the baseline prevalence of myopia and 10-year longitudinal data from the Guangzhou Twin Eye Study (GTES) on the baseline incidence of myopia were utilized.The effect size of outdoor activity intervention was derived from longitudinal data of the Guangzhou Outdoor Activity Longitudinal Study (GOALS). Three intervention strategies were proposed: intervention for children in grades 1 to 6 (Strategy A), intervention for children in grades 1 to 3 (Strategy B), and intervention for children from the last year of kindergarten to grade 3 (Strategy C). Outdoor activity interventions across all strategies included an extra 40 minutes of daily outdoor activity time.Simulated analyses assumed that the prevalence of myopia would decrease with declining incidence and increasing school grade, and the degree of myopia among highly myopic children would decrease with delayed myopia onset.This study was approved by the Ethics Committee of Zhongshan Ophthalmic Center (No.2006-5).Results:With prolonged intervention time, the overall prevalence of myopia in children showed a significant declining trend.After 5 years of implementation, Strategy A resulted in a decrease in myopia prevalence from 34.67% to 25.71%, which decreased to 24.89% after 10 years, with an average annual reduction of 0.98%.Strategies B and C had similar long-term effects, with myopia prevalence after 10 years being 26.00% and 26.20% respectively, with an average annual reductions of 0.87% and 0.85%.Strategy A yielded the greatest reduction in myopia severity, with a decrease of -5.94 D after 5 years and -5.88 D after 10 years in the initial 15-year-old highly myopic individuals.Strategy B followed with -6.08 D and -6.02 D after 5 and 10 years, respectively.Conclusions:Implementing intensified outdoor activity intervention among children in grades 1 to 6 may be the recommended strategy to reduce the overall prevalence of myopia in regions with high rates of myopia among school-aged children.

Objective: To investigate the clinical outcomes of arthroscopic bridging reconstruction of irreparable massive rotator cuff tears using autogenous fascia lata. Methods: From July 2015 to July 2017, a total of 10 cases (4 male and 6 female) who were treated with arthroscopic bridging reconstruction for irreparable massive rotator cuff tears using autogenous fascia lata were retrospectively analyzed. The age before surgery was 61.3±2.9 years (range 57-67 years). There were 7 patients with right shoulders and 3 with left shoulders. The dominate sides were involved in 7 cases. The trauma history was documented in 2 shoulders. The duration of preoperative symptoms was 14.0±13.5 months (1-48 months). The case with revision surgery was not included. The patients were examined with magnetic resonance imaging (MRI) to evaluate the healing of fascia lata patch bridging in the joint at one week, six months, one year and two years after operation. The motion range of shoulder and the clinical scores, including visual analogue scale (VAS), University of California Los Angeles (UCLA) score, Constant-Murley score and American Shoulder & Elbow Surgeons (ASES) score, were measured before surgery and at follow-up duration. Results: All cases were reconstructed the horizontal couple. No perioperative complication was occurred and all surgery were completed safely and successfully. At the end of two years, the score of ASES was 92.2±3.5 (range 88.3-98.3), UCLA 31.6±2.0 (range 28-34), Constant-Murley 85.2±5.4 (range 78-93) with significant difference (t=11.254, P=0.000; t=12.111, P=0.000; t=8.948, P=0.00) comparing with that before surgery. The VAS pain score was 0.6±0.5 (range 0-1) which was significantly lower than that preoperatively (t=11.326, P=0.000). At 2 years after operation, MRI shows that fascia lata patches healed well in 9 patients. However, one case was with re-tear and patch absorption. The range of motion of shoulder was significantly improved in all patients but with different degrees of weakness (3-4). Conclusion Arthroscopic bridging reconstruction using autogenous fascia lata could effectively improve shoulder function in patients with irreparable massive rotator cuff tears. The autogenous fascia lata patch can heal with the help of rotator cuff tissue through bridging reconstruction.

Objective:To investigate the clinical significance of seminal plasma polymorphonuclear neutrophil elastase(PMNE) concentration and semen quality in male infertility.Methods:Semen samples of 941 patients admitted to the andrology department from June 2017 to December 2018 in Dalian Municipal Women and Children′s Medical Center were selected. According to the World Health Organization (WHO) fifth edition standards, the positive group had a leukocyte content ≥ 1 × 10 9/L, and the negative group had a leukocyte content < 1 × 10 9/L; the samples were divided into the inflammatory group and the non-inflammatory group with the PMNE concentration of 600 μg/L as the cut-off point, and the relationship between the PMNE, semen parameters and mycoplasma positive rate was analyzed; the samples were divided into sterile group and normal group according to WHO standard, and the relationships among semen routine parameters, PMNE concentration and mycoplasma positive rate were analyzed. Results:PMNE in the positive group was significantly higher than that in the negative group [(1823.29 ± 557.64) × 10 9/L vs. (480.60 ± 195.36) × 10 9/L], and PMNE concentration was positively correlated with leukocyte content ( P<0.05); the semen quality of the inflammatory group decreased, and the positive rate of mycoplasma was higher than that of the non-inflammatory group [(23.7%(71/299) vs. 11.5%(74/642)] ( P<0.05). The semen quality of the sterile group decreased, and the PMNE and mycoplasma positive rate were both higher than that in the normal group [(1 230.89 ± 489.09) × 10 9/L) vs. (596.78 ± 159.25) × 10 9/L, 34.7%(90/259) vs. 8.1%(55/682)]( P<0.05). Conclusions:There is a good correlation between the concentration of PMNE and the leukocyte content, which can be used as an index to evaluate the male reproductive system infection. The concentration of PMNE is closely related to semen quality, which has clinical value in the diagnosis of male infertility.

BACKGROUND: Few studies have attempted to compare the differences in the prevalence and impact factors of hysterical tendencies (HTs) in adolescents. Thus, the aim of this study was to examine gender differences in the prevalence and impact factors of adolescents' HTs across three eastern Chinese provinces (Anhui, Jiangsu, and Zhejiang). METHODS: A multicenter, school-based, cross-sectional study was conducted in three provinces (Anhui, Jiangsu, and Zhejiang) in China in 2014. The sample included 10,131 middle-school students aged 13-18 years who were randomly selected using a multiphase, stratified, cluster sampling technique. A two-stage appraisal procedure was used to determine the adolescents' HTs. We also designed a multicenter, school-based, case control (1329 cases with 2661 control individuals) study to collect data on the common factors affecting this population using a common protocol and questionnaire. RESULTS: An overall positive rate of HTs among adolescents across the three eastern Chinese provinces studied was found at 13.1% (95% confidence interval (CI) 12.5-13.8%), at 14.5% (95% CI 13.3-15.7%) for females, and at 12.2% (95% CI 11.1-13.4%) for males. Gender-stratified, multiple conditional regression analyses revealed that superstitious beliefs pertaining to life, somatotype, teacher-student satisfaction, and family achievement orientation were significantly linked to HTs only in males, while left-behind adolescents, emotional and social adaptation, teacher-student support, family cohesion, and the Hospital Anxiety and Depression Scale - depression scores were significantly associated with female HTs only. The models indicated that of all the independent variables studied, family medical history was the strongest impact factor for both male HTs (adjusted matched odds ratio (amOR) = 2.92, 95% CI = 1.84-4.86) and female HTs (amOR = 2.74, 95% CI = 1.59-4.98). CONCLUSIONS HTs are prevalent among adolescents in the three eastern Chinese provinces studied. Gender differences in the prevalence and impact factors of HTs are significant in adolescents, and HTs seem to affect more females than males. Therefore, sex-specific intervention programs against HTs in adolescents should be considered to reduce HT prevalence in adolescents by modifying influential social, school, and family factors.
Adolescent ; Adolescent Behavior ; psychology ; China ; epidemiology ; Cross-Sectional Studies ; Female ; Histrionic Personality Disorder ; epidemiology ; psychology ; Humans ; Male ; Prevalence ; Risk Factors ; Sex Factors ; Students ; psychology

Objective To evaluate the role of nicotinamide adenine dinucleotide phosphate oxidase (NADPH oxidase) in the spinal cord in the maintenance of diabetic neuropathic pain in rats.Methods Pathogenfree male Sprague-Dawley rats,aged 2 months,weighing 180-220 g,were used in the study.Diabetes mellitus was induced by intraperitoneal streptozotocin (STZ) 60mg/kg and confirmed by blood glucose ＞ 16.7 mmol/L at 72 h after STZ injection.Twenty diabetic rats were randomly allocated to diabetic neuropathic pain group (DN group,n =10) and apocynin (specific NADPH oxidase inhibitor) group (A group,n =10).Another 10 agematched normal rats served as control group (C group,n =10).Twenty-eight days after STZ injection,apyconin 5 mg/kg was injected intraperitoneally once a day for 7 consecutive days in A group.Paw withdrawal threshold to yon Frey filament stimulation (PWT) was measured before STZ injection (T1) and at 7,14,21,28 and 35 days after STZ injection (T2-6).The rats were sacrificed after PWT was measured at T6 and L4.5 segments of the spinal cord were removed for determination of NADPH oxidase subunits gp91phox and p47phox expression,MAD content and SOD activity.Results Compared with C group,PWT was significantly decreased at T3-5,gp91phox and p47phox expression was up-regulated,MAD content was increased,and SOD activity was decreased in DN and A groups.Compared with DN group,PWT was significantly increased at T6,gp91phox and p47phox expression was downregulated,MAD content was decreased,and SOD activity was increased in A group.Conclusion NADPH oxidase in the spinal cord is involved in the maintenance of diabetic neuropathic pain in rats.

Objective To evaluate the clinical efficacy of transplantation of autologous peripheral blood stem cells(PBSC) for the treatment of toe or heel ulcer and of rest pain in patients with lower limb arterial ischemic diseases.Methods To mobilize patients' own stem cells with G-CSF for 5 days.At the sixth day,PBSC are collected with a blood-cells separator.The PBSC were then intramuscularly injected into ischemic areas of the lower limbs.Results After transplantation,all patients are followed up from 3 to 24 months.The rest pain disappeares in 12 patients,while toe or heel ulcers are cicatrized in 11 cases.However,4 patients lost in following up.ConclusionTransplantation of autologous peripheral blood stem cells is an effective method for the treatment of arterial ischemic disease.

Objective To explore the methods of the endovascular repair of aortic disease(aortic dissection and aortic aneurysm).Methods We retrospectively analysed 64cases of aortic diseases treated with endovascular repair,including 42cases of aortic dissection(38 were Stanford B,4 were Stanford A) and 22 cases of aortic aneurysms.The stent-grafts were set into the aorta cavity to cover the damaged aortic intima through the femoral artery under local or general anesthesia;4 cases also underwent by-pass vascular operations.In 6 cases the left subclavian artery(LSA) was covered by stent-graft at the endovascular therapy without by-pass operation.Results Eighteen cases of immediate inner-leak were found after the stent placement,a rate of 28.13 %(18/64).No other severe complications occurred,such as stent-graft shift or error placement,aortic rupture,conversion to open-operation or paraplegia.The blood flow of all the vital branches of aorta were obviously improved.The mortality in the perioperative period was 6.25 %(4/64),the time of follow-up was 1-78 months(mean 32 months).Reoperation was done in 2 cases of aortic aneurysm group and 2 cases of aortic dissection group.Conclusions The endovascular repair is a good method for aortic disease.The short and middle term result is satistactory,and the long term follow-up needs to be studied.