OBJECTIVE Melatonin(MEL),a natural hormone with broad-spectrum anticancer effects,has been shown to potentiate the therapeutic outcomes of conventional chemotherapy.This study aims to investigate the combined effects of Doxorubicin(DOX)and MEL on head and neck squamous cell carcinoma(HNSCC)cell lines.METHODS The effects of MEL and DOX on cell proliferation in HNSCC cell lines TU686 and CAL-27 were assessed using the MTT assay.The effects of MEL and DOX on reactive oxygen species(ROS)expression levels in HNSCC cell lines were detected using DCFH-DA fluorescent probe.The effects of MEL and DOX on 8-hydroxy-2′-deoxyguanosine(8-oxodG)levels in HNSCC cell lines were measured by enzyme-linked immunosorbent assay(ELISA).The effects of MEL and DOX on γ-H2AX protein levels in HNSCC cell lines were analyzed via Western blot.The effects of MEL and DOX on antioxidant enzymes levels in HNSCC cell lines were evaluated based on spectrophotometry.The effects of MEL and DOX on cell apoptosis in HNSCC cell lines were detected using an ELISA cell death detection kit.RESULTS The MTT assay revealed that MEL significantly enhanced the cytotoxic effects of DOX in HNSCC cell lines(tTU686=13.51,tCAL-27=17.580,all P<0.05).The combination of MEL and DOX markedly increased intracellular ROS levels(FTU686=89.984,FCAL-27=102.853,all P<0.05),while the expression of antioxidant enzymes was significantly reduced(TU686:the F values of CAT,GPx,GR,GST and SOD are 176.035,34.662,20.260,120.105 and 184.254,all P<0.05;CAL-27:the F values are 96.801,177.398,97.849,102.750 and 186.608 respectively,all P<0.05).Furthermore,this combination treatment significantly elevated the expression levels of 8-oxodG(FTU686=200.078,FCAL-27=663.982,all P<0.05)and γ-H2AX(FTU686=192.500,FCAL-27=285.700,all P<0.01)in HNSCC cell lines.Additionally,compared to single-agent treatment,MEL significantly enhanced DOX-induced apoptosis in HNSCC cell lines(FTU686=2718.253,FCAL-27=5185.334,all P<0.01).CONCLUSION The combination of MEL and DOX can enhance cytotoxic effects on HNSCC cell lines,increase intracellular ROS levels,induce DNA oxidative damage,and impair cellular antioxidant defense capacity,thereby effectively promoting HNSCC cell apoptosis.This combination may represent a novel therapeutic approach to improve clinical outcomes in HNSCC.

ObjectiveTo explore the relationships between internet gaming disorder (IGD), interpersonal needs, loneliness, and depression in adolescents through the construction of a chain mediation model, to clarify the underlying mechanisms of these associations, and to provid a theoretical basis for depression prevention and intervention. MethodsBased on the data of the 7th Population Census, using convenient sampling method 1 106 adolescents aged between 10‒19 years in South China (176), North China (147), Central China (332), and East China (451) were selected to conduct a cross-sectional survey, with a ratio of 1∶1∶1.5∶2.5. The survey was conducted with a questionnaire consisting of general information (sex, age, grade, parents’ education level), the Chinese version of the IGDS9-SF, the INQ-15, the short-form of the ULS-8 and the PHQ-9 were used to evaluate the depression status of adolescents. Spearman correlation analysis was used to explore the correlation between the variables. A multiple-mediator model was constructed using IBM SPSS Statistics 22.0 PROCESS to examine the mediating effects of interpersonal needs and loneliness on the relationship between IGD and depression. The significance of the chain mediating effect was tested using the Bootstrap method. ResultsOverall, 39.06% (432/1 106) adolescents experienced depression. The incidence of depression among adolescents with smoking and without smoking was 62.50% and 38.36%, respectively. Similarly, the incidence of depression among adolescents with alcohol consuming and without alcohol consuming was 61.94% and 35.94%, respectively. There were statistically significant differences between IGD, interpersonal needs, loneliness, and depression (P<0.01). The chain mediation model demonstrated a good fit, and the bootstrap test showed that the 95%CI of each mediation path did not include 0, indicating significant mediation effects. The overall effect was 0.337. The direct effect of IGD on depression was significant (effect value=0.138, 95%CI:0.102-0.173, P<0.001). The mediation effects included three paths: ① IGD →interpersonal needs → depression (effect value=0.073, P<0.05), accounting for 21.47% of the total effect;② IGD→ loneliness → depression (effect value=0.093, P<0.05), accounting for 27.35%; and ③ IGD → interpersonal needs → loneliness → depression (effect value=0.036, P<0.05), accounting for 10.59%. ConclusionInterpersonal needs and loneliness independently and jointly mediate the relationship between IGD and depression among adolescents. To reduce depression and improve mental health in this population, measures should be taken to prevent and intervene in IGD, address adolescents’ social and emotional needs, enhance satisfaction of interpersonal needs, and reduce loneliness.

Objective : To investigate the roles of transient receptor potentia1 vanilloid 1 ( TRPV 1) and oxytocin receptor ( OTR) in the mechanism of dysmenorrhea in adenomyosis. Methods : The ectopic endometrium ( EC) and the homologous eutopic endometrium (EU) were selected from 60 patients with adenomyosis surgery , and the control endometrium (CE) of patients without endometriosis was used as control. Streptavidin⁃Peroxidase immunosion of TRPV 1 and OTR was detected by Western blot. The degree of dysmenorrhea was scored by visual analogue scale/score (VAS) , and its correlation with the TRPV 1 and OTR was analyzed. Results : The expression of TRPV 1 and OTR in EC was higher than that in EU and CE (P < 0. 05) , but there was no statistically significant difference between EU and CE. In EC , the expression of TRPV 1 and OTR in the severe dysmenorrhea group was higher than that in the mild and moderate groups (P < 0. 05) , but there was no statistically significant difference between the mild dysmenorrhea group and the moderate group. The expression of TRPV 1 and OTR was positively correlated with the severity of dysmenorrhea ( rs = 0. 280 , P < 0. 05 ; rs = 0. 318 , P < 0. 05) ; the expression of TRPV 1 and OTR was positively correlated ( rs = 0. 287 , P < 0. 05) . Conclusion TRPV 1 and OTR may play a synergistic role in the pathogenesis of dysmenorrhea in patients with adenomyosis , which are important predictors of dysmenorrhea severity and potential therapeutic targets.

Objective:To evaluate the long-term efficacy of AdVance sling bulbar urethral suspension and artificial urethral sphincter (AUS) implantation in the treatment of moderate to severe male stress urinary incontinence.Methods:The clinical data of 12 male patients with urinary incontinence who underwent surgical treatment in Peking University People's Hospital from June 2011 to June 2017 were retrospectively analyzed. The median age was 75(64-80) years. There were 9 cases after radical prostatectomy and 3 cases after transurethral prostatectomy. Patients had a median history of urinary incontinence of 3(1-9) years, and needed an average of 8(5-10) pads per day. Among them, 5 patients had moderate urinary incontinence and 7 patients had severe urinary incontinence. All patients underwent urinary incontinence surgery for the first time. Among the 12 patients, 6 received AdVance sling ball urethral suspension (AdVance group), and 6 received AUS implantation (AUS group). The median age of the AdVance group was 72 (64-73) years. The median number of pads used daily was 6 (5-8) tablets. Urinary incontinence Quality of Life questionnaire (I-QOL) score was (15.0±5.4). Five patients had moderate urinary incontinence and one patient had severe urinary incontinence. In the AUS group, the median age was 78(76-80) years old, the median daily pad use was 8(6-10) tablets, and the I-QOL score was (16.7±5.1), all of which were severe urinary incontinence. The daily pad usage, I-QOL and postoperative complications were recorded at 1 and 5 years after operation.Results:All patients completed the operation successfully. The postoperative follow-up was 5-7 years (mean 5.5 years). In AdVance group, 1 patient with severe urinary incontinence had no significant improvement in postoperative symptoms at 1 year after operation. The other 5 patients showed significant improvement in urinary incontinence symptoms. In the AdVance group, the median number of pads used per day was 2.5 (1-10), and the I-QOL score was (75.0±28.1), which were all significantly improved compared with that before operation ( P<0.05). The median number of pads used per day in the AdVance group 5 years after operation was 2.5(1-10), and the I-QOL score was (78.3±29.3), which were significantly improved compared with those before operation (all P<0.01). In the AUS group, no pad was needed at 1 year after operation, which was significantly improved compared with that before operation ( P<0.01). Urethral erosion occurred in 2 cases 3 years after operation, and the AUS was removed. Urinary incontinence recurred and returned to the preoperative state without reoperation. The other 4 cases did not need to use the pad 5 years after operation. In AdVance group, 3 patients had perineal pain within 3 months after operation, which was related to activity and relieved spontaneously. No wound infection, urethral erosion and other complications occurred. Urethral erosion occurred in 3 cases in AUS group. Conclusions:AdVance sling ball urethral suspension is effective for patients with moderate stress urinary incontinence and has fewer complications. AUS implantation is effective for patients with severe male stress urinary incontinence. However, the long-term complications of this operation may affect the postoperative efficacy.

Compulsive sexual behavior disorder is characterized by the inability to control one′s frequent sexual behaviors or fantasies. It will bring physical pain and psychological distress to the patients and increase the risk of venereal diseases. Research abroad on compulsive sexual behavior disorder is increasing, while domestic studies are rare due to in sufficient attention in clinical practice. To increase the understanding of compulsive sexual behavior disorder, this article reviewed the epidemiology, clinical features, evaluation, diagnosis, and treatment with medications and psychotherapy, providing more comprehensive information on compulsive sexual behavior disorder.

Objective:To evaluate the efficacy for nanoscale microneedle injection of compound betamethasone combined with 308 nm excimer laser in the treatment of stable vitiligo patients.Methods:A total of 80 patients with stable vitiligo were enrolled in Guangzhou Dermatology Hospital from May 2018 to May 2020. There were 40 patients (21 males and 19 females) in control group, aged 17-65 (32.4±1.7) years, and 40 patients (20 males and 20 females) in observation group, aged 18-67 (28.7±1.8) years. The control group was treated with compound betamethasone injection packet combined with 308 nm excimer laser. The observation group was treated with nanoneedle injection of compound betamethasone combined with 308 nm excimer laser. We compared the clinical efficacy and incidence of adverse reactions between the two groups.Results:Comparison of clinical efficacy showed that after 3 months of treatment, the total effective rates of the observation group and the control group were 80.00% and 67.50%, respectively, with significant difference (χ 2=4.560, P<0.05). After 3 months of treatment, the white spot area of the control group was (9.89±1.65) cm 2, which was significantly higher than that of the observation group (7.83±1.78) cm 2 ( t=5.370, P<0.05). Conclusions:The nanoneedle injection of compound betamethasone combined with 308 nm excimer laser in the treatment of stable vitiligo is effective and safe.

Compulsive sexual behavior disorder is characterized by the inability to control one′s frequent sexual behaviors or fantasies. It will bring physical pain and psychological distress to the patients and increase the risk of venereal diseases. Research abroad on compulsive sexual behavior disorder is increasing, while domestic studies are rare due to in sufficient attention in clinical practice. To increase the understanding of compulsive sexual behavior disorder, this article reviewed the epidemiology, clinical features, evaluation, diagnosis, and treatment with medications and psychotherapy, providing more comprehensive information on compulsive sexual behavior disorder.

Extraskeletal Ewing sarcoma is a rare event, and extraskeletal Ewing sarcoma of the thyroid gland is even rarer. It has non-specific clinical manifestation and difficulty in early diagnosis. The diagnosis mainly depends on histology and immunohistochemistry. It possesses the features of high malignancy, high rate of local recurrence, and distant metastasis. Currently, the aggressive multimodal treatment contains surgery, chemotherapy, and radiotherapy. This study presented a case of extraskeletal Ewing sarcoma arising in the thyroid gland of a 30-year-old woman, who presented with supraclavicular mass and sense of dysphagia obstruction in Department of Otolaryngology, Head and Neck Surgery, Second Xiangya Hospital, Central South University in 2018. Imaging studies demonstrated a cystic-solid mass in inferior of the left leaf of thyroid gland and in the posterior of the trachea and esophagus. The patient underwent localized tumor resection. The pathological diagnosis revealed that it was a small round cell tumor, and the immunohistochemistry results were considered to be extraskeletal Ewing sarcoma. Subsequently, the patient was given chemotherapy and local radiation therapy. There was no evidence of tumor recurrence or metastasis.
Adult ; Combined Modality Therapy ; Female ; Humans ; Immunohistochemistry ; Neoplasm Recurrence, Local ; Sarcoma, Ewing/therapy* ; Thyroid Gland

Objective:To establish the urodynamic classification of middle-aged and elderly men with benign prostatic obstruction(BPO), and to analyze the efficacy of transurethral resection of the prostate(TURP) on various types of patients.Methods:A retrospective analysis of middle-aged and elderly male patients with non-neurogenic lower urinary tract symptoms(LUTS) who underwent urodynamic tests from January 2010 to December 2018, including 793 patients with BPO. Urodynamics examination of detrusor without contraction needs to complete cystoscopy to diagnose BPO. During urodynamic examination, the detrusor uninhibited contraction induced by spontaneous or stimulation during the bladder filling period is diagnosed as overactivity of the bladder detrusor(DO), and the LinPURR chart indicates the detrusor underactivity(DU). Based on the persistence of BPO leading to DO, DU, and decreased bladder compliance, 793 male patients with BPO with LUTS were divided into four types, including type Ⅰ(BPO: n=164, 20.7%), type Ⅱ(BPO combined with DO: n=333, 42.00%), type Ⅲ(BPO combined with DU: n=267, 33.7%), type Ⅳ(BPO combined with decreased bladder compliance: n=29, 3.7%). The preoperative comparison between groups showed that the age of type Ⅰ-Ⅳ gradually increased, and the age of type Ⅰ was significantly smaller than other types [(67.3±8.2)years, (69.7±7.7)years, (71.5±7.9)years, (72.4±7.1)years, P<0.05]. Compared with other types, the type Ⅰ’s IPSS-S[(9.1±3.6)points vs.(10.4±3.1) points, (9.2±3.3) points, (10.4±3.1)points, P<0.05], IPSS-V[(13.5±3.4) points vs. (14.2±3.5)points, (14.0±3.5)points, (14.2±2.9)points, P<0.05], IPSS scores[(22.6±5.4)points, (24.7±4.9)points, (23.1±5.3)points, (24.6±4.7)points, P<0.05] were significantly lower than other groups, the maximum bladder capacity [(332.6±83.2)ml vs.(221.4±80.8)ml, (286.7±108.2)ml, (242.3±103.4)ml, P<0.05], the functional bladder capacity was significantly higher than other types[(215.2±90.0)ml, (148.5±76.0)ml, (154.9±87.2)ml, (121.2±72.9)ml, P<0.05]. Type Ⅱ’s IPSS-S[(10.4±3.1)points vs.(9.1±3.6)points, (9.2±3.3)points, P<0.05], nocturia frequency[(3.7±1.8)times vs.(3.2±1.8)times, (3.2±1.6)times, P<0.05], IPSS score[(24.7±4.9)points vs.(22.6±5.4)points, (23.1±5.3)points, P<0.05], quality of life scores [(4.9±0.9) points, (4.6±0.9)points, (4.6±0.9)points, P<0.05] was significantly higher than type Ⅰ and type Ⅲ ( P<0.05). Type Ⅲ and Ⅳ had higher residual urine than type Ⅱ[(121.3±96.4)ml, (121.3±96.4)ml vs.(71.2±73.5)ml, P<0.05]. Type Ⅳ’s IPSS-S[(10.4±3.1)points vs. (9.1±3.6)points, (9.2±3.3)points, P<0.05], IPSS-V[(14.2±2.9) points vs.(13.5±3.4)points, (14.0±3.5)points, P<0.05], the frequency of nocturia[(3.8±1.9)times vs.(3.2±1.8)times, (3.2±1.6)times, P<0.05] was significantly higher than that of type Ⅰ and type Ⅲ, and the quality of life score was higher than type Ⅰ and type Ⅲ[(4.3±0.8)points vs.(4.7±0.9)points, (4.6±0.9)points, P<0.05]. type Ⅱ and type Ⅳ’s bladder compliance[(21.4±24.2)ml/cmH 2O, (11.0±11.4)ml/cmH 2O vs.(33.9±23.7)ml/cmH 2O, (33.1±32.7)ml/cmH 2O, P<0.05], maximum bladder capacity[(221.4±80.8)ml, (242.3±103.4)ml vs.(332.6±83.2)ml, (286.7±108.2)ml, P<0.05], functional bladder capacity[(148.5±76.0)ml, (121.2±72.9)ml vs.(215.2±90.0)ml, (154.9±87.2)ml, P<0.05] were significantly less than type Ⅰ and type Ⅲ( P<0.05). From November 2016 to November 2018, 60 middle-aged and elderly male patients with confirmed BPO and TURP were selected, including type Ⅰ( n=17, 28.3%), type Ⅱ ( n=23, 38.3%), and Ⅲ type ( n=11, 18.3%), Ⅳ type( n=9, 15.1%). Type IV patients are significantly older than other types ( P<0.05), bladder compliance is significantly worse than other types( P<0.05), the maximum bladder capacity is smaller than other types( P<0.05). The follow-up started 3 months after the operation. The content of the follow-up included IPSS, IPSS-S, IPSS-V, nocturia frequency, undisturbed sleep time, nocturia quality of life score, and life quality score. Results:The IPSS scores of type Ⅰ, type Ⅱ, and type Ⅲ after TURP were significantly improved compared with preoperative(19.8±6.2 vs.3.4±1.8; 21.9±5.2 vs.4.6±2.6; 21.5±6.2 vs.5.7±4.6, P<0.05), type Ⅳ urine storage symptom score (9.1±4.1 vs.4.3±3.7), nocturia frequency(3.6±1.5vs.2.3±1.6), nocturia quality of life score (25.3±6.9 vs.31.4±13.7) Compared with preoperatively, there was no significant improvement( P>0.05). The quality of life score improvement of type Ⅳ patients was significantly lower than that of type Ⅰ, type Ⅱ, and type Ⅲ (10.9±9.1 vs.12.2±9.0, 14.4±5.7, 12.7±5.8, P<0.05). The IPSS score of type Ⅳ patients was significantly higher than that of type Ⅰ(7.0±5.8 vs.3.4±1.8), and the nocturia quality of life score was significantly lower than that of each group (31.4±13.7 vs.37.5±4.2, 38.7±3.5, 37.8±3.8, P<0.05). Conclusions:For middle-aged and elderly men with BPO, we divide them into four types based on the results of urodynamic examinations, type Ⅰ(simple BPO), type Ⅱ(BPO combined with DO), type Ⅲ(BPO combined with DU), type Ⅳ(BPO combined with bladder compliance decline). Type Ⅰ patients have the best bladder function, and TURP has the best effect; type Ⅱ has a high symptom score and poor quality of life, and can benefit after TURP; type Ⅲ bladder function is poor, and surgery should be performed as soon as possible to prevent further deterioration of bladder function; type Ⅳ bladder function is the best poor, IPSS score and quality of life score are high, TURP surgery is not effective.

Objective:To investigate whether coxsackievirus A 16 (CVA16) infection would affect the expression of N6-methyladenosine (m 6A) methylation-related proteins in human bronchial epithelial cells (16HBE), ICR suckling mice and SCRBA2 humanized mice and influence their subcellular localization. Methods:CVA16 was used to infect 16HBE cells at a multiplicity of infection (MOI) of 0.1 and mice at 10 7 CCID 50/ml. Changes in the expression of methyltransferases, demethylases and methylated reading proteins were analyzed by Western blot. Cellular localization of these proteins was observed using immunofluorescence. Results:The expression of m 6A methylation-related proteins was gradually reduced in CVA16-infected cells with time, but showed no obvious change in ICR suckling mice or SCRBA2 humanized mice. After infection, m 6A methylation-related proteins were redistributed in both the nucleus and cytoplasm and even degraded. Conclusions:CVA16 replication in host cells altered the expression and cellular localization of m 6A methylation-related proteins, which indicated that m 6A modification might be a new potential target for enterovirus therapy.