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 investigate the related influence factors of the main extended direction of the pituitary macroadenoma in the vertical direction.Methods Clinical data of 184 pituitary macroadenoma patients were collected and analyzed retrospectively.The main extended direction in the vertical direction of the tumor was taken as the dependent variables.Patients were divided into two groups according to the suprasellar extension value of each tumor,(ie:suprasellar extension value＞0 and suprasellar extension value≤0).10 selected indicators (age,sex,tumor type,diameter of diaphragmatic opening,sphenoid sinus type,sella type morphology,main sphenoid sinus septum bias,maximum width of sphenoid sinus septum,tumor cyst,number of longitudinal sphenoid sinus septum) were taken as independent variables and the factors which may influence the main extended direction were analyzed and selected by logistic regression method.Results Among the 184 patients,there were 121 cases extending mainly to the suprasellar direction,while the left cases extending mainly to the opposite direction.Statistical analysis showed the tumor type (P=0.026),sphenoid sinus type (P=0.003),sella type morphology (P=0.046),diameter of diaphragmatic opening (P=0.003) and maximum width of the sphenoid sinus septum (P=0.009) were the independent predictors influencing the main expansion direction of pituitary macroadenomas in the vertical direction.Conclusions The pituitary macroadenoma is more likely to expand infrasellar in patients with sellar or sellaoccipital sphenoid sinus,sac sella turcica morphology,GH adenoma,smaller diaphragmatic opening diameter and narrower width of sphenoid sinus septum.The pituitary macroadenoma is more likely to expand suprasellar in patients with presellar sphenoid sinus,wok and cylinder sella turcica morphology,nonGH adenoma,larger diaphragmatic opening diameter and wider width of sphenoid sinus septum.

In this study, we used next-generation sequencing methods to screen 300 individuals for BRCA1 and BRCA2. A novel mutation (c.849dupT) in BRCA2 was identified in a female patient and her unaffected brothers. This mutation leads to the truncation of BRCA2 functional domains. Moreover, BRCA2 mRNA expression levels in mutation carriers are significantly reduced compared to noncarriers. Immunofluorescence and western blot assays showed that this mutation resulted in reduced BRCA2 protein expression. Thus, we identified a novel mutation that damaged the function and expression of BRCA2 in a family with breast cancer history. The pedigree analysis suggested that this mutation is strongly associated with familial breast cancer. Genetic counsellors suggest that mutation carriers in this family undergo routine screening for breast cancer, as well as other malignancies, such as prostate and ovarian cancer. The effects of this BRCA2 mutation on drug resistance should be taken into consideration during treatment.
Blotting, Western ; BRCA2 Protein ; Breast Neoplasms* ; Breast* ; Drug Resistance ; Female ; Fluorescent Antibody Technique ; Genes, BRCA2 ; High-Throughput Nucleotide Sequencing ; Humans ; Mass Screening ; Nonsense Mediated mRNA Decay* ; Ovarian Neoplasms ; Pedigree ; Prostate ; RNA, Messenger ; Siblings

Objective To study the estimated value of general pituitary hormone levels and "overall levels of pituitary hormone" in patients with pituitary adenoma.Methods Sixty-six patients presented with non-function pituitary adenomas,admitted to our hospital from January 2009 and April 2013,were chosen in our study.Pre-and post-operative hormonal levels and MR imaging data were collected.Patients were divided into two groups:macroadenoma (1 cm＜diameter＜3 cm) group and huge adenoma (diameter＞3 cm) group,and the patients were divided into subtotal resection group (resection rate＞60％) and partial resection group (resection rate＜60％).Self-made scale of "overall levels of pituitary hormone" was performed to assess the remnant pituitary function.The levels for 6 kinds of pituitary hormones and "overall levels of pituitary hormone" were compared between each two groups.Results (1) The levels of 6 kinds of pituitary hormones between the macroadenoma group (n=38) and huge adenoma group (n=28) showed no significant difference before surgery (P＞0.05);the per-operative "overall levels of pituitary hormone" were statistically different between the macroadenoma group (19.59±2.71) and huge adenoma group (18.07±2.00,P＜0.055);there were 13 patients (34.2％) from macroadenoma group and 17 (60.7％) from huge adenoma group having one or more kinds of pituitary hormones lower than normal levels,with significant difference (P＜0.05).(2) The levels of 6 kinds of pituitary hormones between subtotal resection group (n=57) and partial resection group (n=9) showed no significant difference after surgery (P＞0.05);the post-operative "overall levels of pituitary hormone" in the subtotal resection group were significantly higher than those in the partial resection group (P＜0.05);there were 34 patients (59.6％) from subtotal resection group and 2 (22.2％) from partial resection group having one or more kinds of pituitary hormones lower than normal levels,without significant difference (P＜0.05).Conclusions The "overall levels of pituitary hormone",in which 6 kinds of pituitary hormones are seen as a whole,can assess the remnant pituitary function in pituitary adenoma patients more accurately than evaluation of the 6 kinds of pituitary hormone levels separately.

Objective To observe the clinical effects of therapy to neonatal jaundice by Yinzhihuang particles.Methods72 cases from July 2015 to December 2016, were randomly divided into two groups and made all 36 cases in the control group, children in the control group given blue light therapy observation group were treated in the control group on the basis of Yinzhihuang particle therapy, follow-up and record two serum C-reactive protein (CRP), total bilirubin (TBIL), γ-alanine amino acyltransferase (γ-GT), alkaline phosphatase (AKP) and free fatty acid (FFA) levels and incidence of adverse reactions, the use ofstatistical methods for data analysis.Results① observation group after treatment CRP,TBIL, γ-GT values were better than the control group, and the difference was significant (P<0.05).② observation group in the AKP, FFA values after treatment than the control group, and the difference was significant (P<0.05).③ observation group rash during treatment, the incidence of diarrhea were (0.00%, 2.78%), were lower than the control group (11.11%, 16.67%), and the difference was significant (P<0.05).ConclusionYinzhihuang particle treatment of neonatal jaundice effect is good, worthy of further research and application.

Objective To explore the effect of nonfunctioning pituitary adenoma (NFPA)apoplexy on growth rate of residual tumor after transsphenoidal operation.Methods The follow-up MR imaging data of 57 patients with NFPA who had residual tumors after transsphenoidal operation,admitted to our hospital from May 2005 to May 2015,were analyzed retrospectively.The tumor volume doubling time (TVDT) of residual tumors,rapid growth rate and apoplexy/tumor size ration were calculated.The relations of tumor rapid growth rate with existence of adenoma apoplexy,course of adenoma apoplexy and apoplexy/tumor size ration were compared.Results There were 30 patients with NFPA apoplexy and 27 without adenoma apoplexy.Postoperative follow-up indicated enlarged residual tumors in 49 patients,and shrank ones in 8 patients.The mean TVDT was (1305.82±1685.32) d.The rapid growth rate of residual tumors in NFPA apoplexy group (56.67％) was not significantly increased as compared with that in non-NFPA apoplexy group (66.67％,P＞0.05).The rapid growth rate of subacute NFPA apoplexy group (81.82％) was significantly higher than that of chronic NFPA apoplexy group (36.84％,P＜0.05).The rapid growth rate of group of apoplexy/tumor size ration less than 12％ (40％) was not significantly different as compared with that of rapid growth rate of group of apoplexy/tumor size ration more than 12％ (66.67％,P＞0.05).Conclusions Adenoma apoplexy is one of the factors that affect the growth rote of residual tumors ofNFPA after transsphenoidal operation.For patients with NFPA apoplexy in subacute or chronic phase,if their symptoms are mild,they can be followed up regularly.

Objective To evaluate the surgical strategy for giant pituitary adenomas apoplexy complicated with obstructive hydrocephalus.Methods Twenty-three patients with giant apoplectic pituitary adenomas associated with obstructive hydrocephalus,admitted to our hospital from January 2010 to March 2015,were chosen;their clinical and surgery data were retrospectively summarized.Results Transsphenoidal microsurgery was conducted in 22 patients and craniotomy in one.All tumors showed cystic degeneration and soft texture.Seven patients had faint yellow or hyaline cyst fluid and 16 had soybean sauce or dark red cyst fluid.Near-total tumor resection was achieved in 2 patients (8.7％),subtotal resection in 16 (69.6％),and partial resection in 5 (21.7％).Twenty-three patients were followed up for 4-38 months,one patient accepted repeated operation for residual rumors,5 had postoperative adjuvant radiation therapy,and no other patients showed re-growth or recurrence.Postoperatively,there was no long-term cerebrospinal fluid leakage and diabetes insipidus,with hydrocephalus disappeared in 100％,visual improved in 60.9％,and headache relieved in 81.8％.Conclusions Pituitary adenoma presented with apoplexy and concurrent obstructive hydrocephalus is often soft.Transsphenoidal microsurgery is the preferred safe and effective method which can relieve hydrocephalus and achieve improved clinical symptoms.

Objective To analyze the occurrence and location of posterior pituitary bright spot (PPBS) and its influence factors by analyzing the magnetic resonance T1-weighted imaging (T1WI) in patients with pituitary adenoma.Methods One hundred and twenty-three patients with pituitary adenoma,admitted to our hospital from September 2012 to September 2014,were collected in our study.All patients were performed T1WI and T2WI sagittal,coronal and axial scan and enhanced scan at SE sequence before operation.The occurrence and location of PPBS of the pituitary gland were observed;the clinical data of these patients from PPBS-visible group and PPBS-non-visible group were analyzed and compared.Re.sults Of the 123 patients,the PPBS-visible group included 98 patients (79.7％) and the PPBS-non-visible group included 25 patients (20.3％).The adenoma shapes were classified into hourglass-type (n=43),barrel-type (n=63) and wedge-type (n=17).The occurrencerateofPPBSin barrel-type patients was significantly lower than hourglass-type patients (P＜0.05);the signal intensity ratio of PPBS and pons in barrel-type patients and wedge-type patients was significantly higher than that in the hourglass-type patients (P＜0.05).Adenoma volume and height of the PPBS-visible group was significantly smaller than those in the PPBS-non-visible group (P＜0.05).The distribution of different adenoma types was significantly different between patients from PPBS-visible group and PPBS-non-visible group (P＜0.05).Conclusion The posterior lobe of pituitary could be displayed satisfactorily at T1WI,and appearance of PPBS is related to the morphology,volume and height of pituitary adenoma.

Blood Gas Analysis ; Hepatopulmonary Syndrome ; therapy ; Humans ; Male ; Middle Aged ; Portasystemic Shunt, Transjugular Intrahepatic ; Treatment Outcome