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.

Humans ; Aripiprazole/therapeutic use* ; Schizophrenia/drug therapy* ; Antipsychotic Agents/therapeutic use* ; Risperidone ; China ; Treatment Outcome

Objective:To explore the facilitating and inhibitory factors influencing the behavior of young patients to share medical electronic word-of-mouth (eWOM) on internet platforms, so as to provide insights for the improvement of healthcare quality.Methods:In May 2022, 271 undergraduate students from universities in Zhejiang province were selected by convenient sampling to survey their motivations to share eWOM with a self-designed questionnaire. Multiple regression analysis was used to examine the impact of different motivational factors on the sharing intention of young patients.Results:Only 16 respondents (5.9%) had previously published medical eWOM. Egoistic motivation, altruistic motivation, medical experience, and comment habits were significant factors that promoted patients to share eWOM, with egoistic motivation ( β=0.212, P<0.001) having the greatest impact and comment habit ( β=0.139, P=0.003) having the least impact. Distrust, low self-efficacy and involvement, perceived reluctance, and perceived uselessness were significant factors inhibiting patients from publishing eWOM. Of them, distrust ( β=-0.161, P<0.001) and perceived reluctance ( β=-0.161, P=0.001) had the greatest impact, and low self-efficacy and involvement had the least impact ( β=-0.134, P=0.003). Conclusions:To enhance the positive attitude of young patients towards sharing eWOM, it is important to focus on their personal benefits and provide high-quality healthcare experiences. Building trust among patients in the platform is crucial, and efforts should be made to reduce operational barriers. Additionally, educating and raising awareness among young patients regarding the significance and influence of healthcare reviews is important.

Objective:This study aims to explore the relationship between non-suicidal self-injurious (NSSI) behaviors and childhood trauma and peer rejection in adolescents with depressive disorders and, to examine whether childhood trauma and peer rejection can predict NSSI behaviors in these adolescents.Methods:A total of 412 depressed adolescents (263 with NSSI and 149 without NSSI) were included in the test data set, while another 161 depressed adolescents (99 with NSSI and 62 without NSSI) were in the validation set. This study firstly analyzed the differences in the scores of the Children's Depression Inventory (CDI), Childhood Trauma Questionnaire (CTQ), and Social Peer Rejection Scale (SPR) between the two groups using the test set. Then, a hierarchical logistic regression model was used to analyze the independent effects of these environmental factors on NSSI behaviors and to determine the diagnostic model. Finally, the diagnostic model was applied using the validation data set to calculate the actual predictive efficacy of the model.Results:Compared to those without NSSI, adolescent patients with NSSI showed significantly higher scores in CDI ( t=10.04, P<0.001), CTQ ( t=9.11, P<0.001), SPR ( t=5.30, P<0.001), and their subscale scores. Then, the scores of the low self-esteem factor of CDI ( OR=1.12, P=0.002), the emotional neglect factor of CTQ ( OR=1.08, P=0.037), and the insult factor ( OR=1.10, P=0.050) and somatic aggression factor ( OR=0.89, P=0.049) of SPR were significantly associated with NSSI behaviors. The diagnostic model was well established (area under the ROC curve=0.84, P<0.001). In addition, in the validation data set, the diagnostic model had a significant predictive effect (area under the ROC curve=0.85, P<0.001). Conclusion:Childhood emotional neglect and peer insult might be crucially influential factors triggering NSSI behaviors among adolescents with depressive disorders. Childhood trauma and peer rejection were of considerable importance when diagnosing and predicting the development of NSSI behaviors in depressive adolescents.

Objective:This study aims to explore the relationship between non-suicidal self-injurious (NSSI) behaviors and childhood trauma and peer rejection in adolescents with depressive disorders and, to examine whether childhood trauma and peer rejection can predict NSSI behaviors in these adolescents.Methods:A total of 412 depressed adolescents (263 with NSSI and 149 without NSSI) were included in the test data set, while another 161 depressed adolescents (99 with NSSI and 62 without NSSI) were in the validation set. This study firstly analyzed the differences in the scores of the Children's Depression Inventory (CDI), Childhood Trauma Questionnaire (CTQ), and Social Peer Rejection Scale (SPR) between the two groups using the test set. Then, a hierarchical logistic regression model was used to analyze the independent effects of these environmental factors on NSSI behaviors and to determine the diagnostic model. Finally, the diagnostic model was applied using the validation data set to calculate the actual predictive efficacy of the model.Results:Compared to those without NSSI, adolescent patients with NSSI showed significantly higher scores in CDI ( t=10.04, P<0.001), CTQ ( t=9.11, P<0.001), SPR ( t=5.30, P<0.001), and their subscale scores. Then, the scores of the low self-esteem factor of CDI ( OR=1.12, P=0.002), the emotional neglect factor of CTQ ( OR=1.08, P=0.037), and the insult factor ( OR=1.10, P=0.050) and somatic aggression factor ( OR=0.89, P=0.049) of SPR were significantly associated with NSSI behaviors. The diagnostic model was well established (area under the ROC curve=0.84, P<0.001). In addition, in the validation data set, the diagnostic model had a significant predictive effect (area under the ROC curve=0.85, P<0.001). Conclusion:Childhood emotional neglect and peer insult might be crucially influential factors triggering NSSI behaviors among adolescents with depressive disorders. Childhood trauma and peer rejection were of considerable importance when diagnosing and predicting the development of NSSI behaviors in depressive adolescents.

Objective To investigate the clinical features and treatment principles of inflammatory myofibroblastic tumor of the urinary bladder (IMTUB).Methods From April 2013 to October 2016,6 cases of IMTUB patients were analyzed retrospectively.All cases were presented with gross hematuria.4 cases underwent ultrasonography,of which 3 cases showed solid mass in bladder,1 case showed inflammatory change.6 cases underwent CT examination,3 cases with bladder cancer,1 case with bladder sarcoma,1 case with malignant transformation of adenoma,1 case with rich blood supply.No lymph node metastasis.Bladder occupying lesions were considered in 2 cases of MRI examination.5 cases of cystoscopy showed bladder solid mass.In 6 cases involved,2 patients received partial cystectomy,2 patients underwent transurethral resection of bladder tumor,1 patient underwent radical resection of urachal carcinoma and the other one was treated with chemotherapy.Results Immunohistochemical staining was positive in ALK (100.0％) 、Vimentin(100.0％) 、CK(100.0％) 、SMA (83.3％) 、EMA(66.7％) and Ki-67 (5％-30％),negative in S-100 and Desmin.Final pathological diagnosis was IMTUB.So far,neither recurrence nor metastasis has been detected for 6 ～ 42 months in 5 cases and the other one lost to follow-up.Conclusions IMTUB is a kind of rare benign tumor of bladder.The golden standard of diagnosis is pathological diagnosis.Surgical resection is the first choice for treatment.Recurrence and metastasis are after the surgery treatment.All patients should be followed up closely.

Objective To explore the psychological behavior features between different sexual children with oppositional defiant disorder(ODD).Methods The subjects were sampled from grade 1 to 5 in a primary school in Ji-nan,Shandong Province.According to the diagnosed criteria,42 pupils were diagnosed ODD,which was the study group,and 556 pupils without ODD became the control group.The pupils and their families were investigated and as-sessed by using Achenbach Child Behavior Checklist (CBCL).Results According to CBCL,there was extremely sig-nificantly higher score of depression,obsessive -compulsive,hyperactive,aggressive,interpersonal behaviors in ODD boys [(5.00 ±3.73)scores,(4.88 ±3.65)scores,(5.21 ±3.49)scores,(1 0.1 0 ±6.85)scores,(2.88 ±1 .99) scores]than those in healthy control group [(1 .65 ±2.61 )scores,(1 .91 ±2.65)scores,(2.46 ±2.63)scores, (3.95 ±4.52)scores,(1 .34 ±1 .61 )scores](t =4.31 ,3.90,4.76,4.33,4.40;P =0.000,0.000,0.001 ,0.000, 0.000).There was significantly higher score of symptoms of somatization,indiscipline,schizoid -like behaviors in ODD boys with [(2.38 ±2.50)scores,(2.63 ±2.70)scores,(3.1 7 ±2.35)scores]than those in healthy control group [(0.85 ±1 .63)scores,(0.1 3 ±1 .76)scores,(1 .51 ±1 .72)scores](t =2.94,2.85,3.37;P =0.007,0.009, 0.002).There was extremely significantly higher score of depression,communication disorder behaviors in ODD girls [(5.44 ±4.1 2)scores,(3.1 1 ±2.93)scores]than those in healthy control group with [(2.50 ±3.34)scores, (1 .36 ±2.08)scores](t =3.57,3.38;P =0.000,0.001 ).A significantly higher score of hyperactive,aggression, cruelty behaviors in ODD girls [(4.67 ±4.41 )scores,(9.33 ±7.82)scores,(1 .1 7 ±1 .79)scores]than those in healthy control group [(1 .87 ±2.38)scores,(3.1 9 ±4.08)scores,(0.24 ±0.66)scores](t =2.67,3.30,2.1 8;P =0.01 6,0.004,0.043).Conclusions According to CBCL,there were more psychological behavior problems in ODD children than healthy children.A significantly higher difference was found in different gender.