OBJECTIVE To evaluate the mechanisms underlying the antidepressant effect of ZBH2012001,a novel serotonin and norepinephrine reuptake inhibitor(SNRI),in general and its ability to enhance monoaminergic transmission and suppress neuroinflammation in particular.METHODS① Male ICR mice were divided into vehicle(distilled water),duloxetine(DLX,10 or 20 mg·kg-1)and ZBH2012001(5,10 and 20 mg·kg-1)groups.One hour following ig administration,the antidepressant effect of ZBH2012001 was evaluated using the tail suspension test(TST)and forced swimming test(FST).② Radioligand binding assay was conducted to evaluate the affinity of ZBH2012001 for human serotonin transporters(hSERTs)and human norepinephrine transporters(hNETs).③ Mice were divided into vehicle(distilled water),DLX(10 or 20 mg·kg-1)and ZBH2012001(5,10 and 20 mg·kg-1)groups.One hour following drug administration,the 5-hydroxytryptophan(5-HTP)-induced head-twitch test or yohimbine-induced lethality test were performed to evaluate the effect of ZBH2012001 on the function of the 5-hydroxytryptamine(5-HT)and norepinephrine(NE)systems.④ Mice were divided into vehicle(distilled water+0.1%acetic acid),reserpine model(distilled water+reserpine 5 mg·kg-1),DLX(DLX 20 mg·kg-1+reserpine 5 mg·kg-1)and ZBH2012001(ZBH2012001 5,10 and 20 mg·kg-1+reserpine 5 mg·kg-1)groups.One hour following drug administration,reserpine was injected intraperitoneally to establish a monoamine-depletion model.The ptosis,akinesia,and hypothermia assays were performed to evaluate the effect of ZBH2012001 on the down-regulation of the reserpine-induced monoamine system.The TST in mice was used to evaluate the effect of ZBH2012001 on reserpine-induced depressive-like behavior while high-performance liquid chromatography with electrochemical detection(HPLC-ECD)was used to measure the levels of monoamines and their metabolites in the hippocampal tissue of reserpine-induced monoamine-depletion mice.ELISA was employed to detect the contents of tumor necrosis factor-alpha(TNF-α)and interleukin-6(IL-6)in the hippocampal tissue of reserpine-induced monoamine-depletion mice.Western blotting was used to assess the expressions of ionized calcium-binding adapter molecule-1(Iba-1)and nuclear factor-kappa B(NF-κB)in the hippocampal tissue of reserpine-induced monoamine-depletion mice.RESULTS ① Compared with the vehicle group,ZBH2012001(5,10 and 20 mg·kg-1)significantly reduced the immobility time both in the TST in mice(P<0.01,respectively),and ZBH2012001(20 mg·kg-1)and in the FST in mice(P<0.05).② ZBH2012001 competitively inhibited the binding of[3H]-imipramine to hSERTs and[3H]-nisoxetine to hNETs,with the half maximal inhibitory concentration(IC50)values of 84.95 and 712.90 nmol·L-1,respectively.③Com-pared with the vehicle group,ZBH2012001(10 and 20 mg·kg-1)significantly increased the head twitches induced by 5-HTP in mice(P<0.01,respectively)and increased the mortality rate in mice induced by yohimbine(P<0.05,P<0.01).④ In the reserpine-induced monoamine-depletion model in mice,compared with the vehicle group,mice in the reserpine model group exhibited ptosis,akinesia and hypothermia feature(P<0.01,respectively),significantly prolonged immobility time in the TST(P<0.01),significantly decreased the levels of NE,5-HT and dopamine(DA)(P<0.05,P<0.01),significantly increased the metabolic conversion rate of 5-HT and DA(P<0.01,respectively),significantly elevated levels of TNF-α and IL-6(P<0.05,respectively),and significantly increased expressions of Iba-1 and NF-κB(P<0.05,respectively)in the hippocampus.Compared with the model group,ZBH2012001(5,10 and 20 mg·kg-1)significantly antagonized ptosis and hypothermia behaviors induced by reserpine(P<0.01,respectively),ZBH2012001(10 and 20 mg·kg-1)significantly shortened the immobility time in reserpine-treated mice(P<0.05,P<0.01),ZBH2012001(20 mg·kg-1)significantly increased the levels of NE and 5-HT in the hippocampus of reserpine-treated mice(P<0.05,respectively),decreased the metabolic conversion rate of 5-HT(P<0.05),significantly reduced the contents of TNF-α and IL-6 in the hippocampus of reserpine-treated mice(P<0.05,respectively),ZBH2012001(5,10 and 20 mg·kg-1)significantly reduced the expression of Iba-1 protein in the hippocampus of reserpine-treated mice(P<0.01,respec-tively),and ZBH2012001(20 mg·kg-1)significantly reduced the expression of NF-κB protein in the hippocampus of reserpine-treated mice(P<0.05).CONCLUSION ZBH2012001 exerts its antidepres-sant effect through a dual mechanism involving monoamine enhancement and inflammation suppres-sion.

Objective:To explore the effect of family empowerment program combined with deglutition exercises in patients with deglutition disorders.Methods:From February 2019 to February 2021, a total of 107 patients with deglutition disorders admitted to Xinxiang Central Hospital were enrolled by convenience sampling method and divided into the observation group (54 cases) and the control group (53 cases) using random number table method. The control group received routine nursing and deglutition intervention, and the observation group received family empowerment program combined with deglutition intervention on the basis of routine nursing. The standardized swallowing assessment (SSA) , mini nutritional assessment short-form (MNA-SF) , swallowing quality of life questionnaire (SWAL-QOL) scores and the incidence of adverse events of the two groups were compared before and after intervention.Results:After intervention, MNA-SF score and SWAL-QOL score of the observation group were higher than those of the control group, while SSA score, incidence of respiratory aspiration and aspiration pneumonia of the observation group were lower than those of the control group , the differences were statistically significant ( P<0.05) . Conclusions:The family empowerment program combined with deglutition exercises can improve patients' deglutition function and nutrition status, reduce the risk of respiratory aspiration and aspiration pneumonia, and improve patients' quality of life.

Characterized by impaired neuromuscular transmission, congenital myasthenic syndromes (CMS) are a group of genetic disorders.The main manifestations include fatigue and weakness of skeletal muscle, with most onset in infant or early childhood.The common cause of death is respiratory failure, with high disability rate.With the improvement of gene sequencing technology and the in-depth study on the structure and function of pathogenic proteins, the pathogenesis of the disease has been deeply understood in the past 20 years.Early diagnosis and treatment can significantly improve the symptoms in patients.In this manuscript, the etiology, clinical characteristics, diagnosis and treatment of CMS are reviewed.

Objective:To describe clinical characteristics, genetic mutation and therapeutic response of a family diagnosed as slow-channel congenital myasthenia syndrome (SCCMS) and analyze the factors of the efficacy of channel blockers therapy.Methods:Clinical data and therapeutic response in three patients from a family of SCCMS from Department of Neurology, Xuanwu Hospital, Capital Medical University in May 2017 were collected. The clinical data, mutations and response to therapy of all literature SCCMS cases in the English database of Pubmed and Chinese database of Wanfang until December 31, 2018 were analyzed statistically.Results:The proband was a 48-year-old female who referred to Xuanwu Hospital for limb weakness for 40 years. The proband′s elder daughter presented with onset of the birth and delayed motor milestones, scoliosis and difficulty in walking. The younger daughter was born healthy with normal motor milestones, while fatigue and weakness gradually appeared. The antibodies of myasthenia gravis were negative. No repetitive compound muscle action potentials (CMAP) were detected in three patients. Repetitive nerve stimulation showed decrements. Gene test revealed heterozygous mutation of CHRNE p.εV279F, a known pathogenic mutation of SCCMS. Seventeen SCCMS cases were reported in literature. A total of 20 patients with SCCMS were described in terms of clinical manifestation, mutation, drug therapy and efficacy in detail. According to the literature description, they were divided into significant benefit group and mild to modest benefit group to channel blocker therapy. The age of onset in 10 patients with significant benefit was 1.50 (0.75, 28.25) years from birth to 43 years, and that in 10 patients with mild to modest benefit was 2.50 (0, 6.25) years from birth to 11 years. There was no significant difference between the two groups. The age at the initial channel blocker therapy in the group with significant benefit was (23.40±13.29) years from 12 to 43 years, whereas that in the group with mild to modest benefit was (34.10±13.43) years from 20 to 62 years, and there was no significant difference between the two groups. The delay time of treatment (age at the beginning of treatment with channel blockers-age of onset) in patients with significant benefit was 13.0 (10.25, 15.00) years, which was 32.50 (19.25, 38.00) years in patients with mild to modest benefit ( Z=-3.374, P=0.000). According to the response of cholinesterase inhibitor, eight patients were in the effective group, 10 patients were in the ineffective group and two patients were without cholinesterase inhibitor. The age of onset in the effective group was 0 (0, 4.75) years, while that in the ineffective group was 6.50 (1.00, 28.25) years ( Z=-2.315, P=0.021).The age of treatment with channel blockers was (27.90±12.99) years in the effective group and (32.00±13.21) years in the ineffective group, and there was no significant difference between the two groups. The delay time of channel blocker treatment in effective group was (30.25±11.07) years, while that in ineffective group was (14.30±9.60) years ( t=-3.274, P=0.005). Conclusions:In SCCMS, the effect of channel blockers was related to the delay time of treatment. Channel blocker was more effective the sooner it was started after the onset of symptoms. The average age of onset of SCCMS patients with positive responses to cholinesterase inhibitor was younger, but the delay time of channel blocker therapy was longer, resulting in poor therapeutic effect.

Objective To investigate risk factors related to postoperative death of patients with rectosigmoid junction tumor perforation.Methods The clinical data of 76 cases with rectosigmoid junction tumor perforation confirmed by laparotomy from January 2000 to October 2015 were collected.Results Of the 76 cases,17 patients died postoperatively,the mortality rate was 22％,the single factor analysis showed that age(x2 =4.649,P =0.031),duration of abdominal pain(x2 =8.218,P =0.016),severe heart and lung diseases(x2 =11.996,P =0.007),circulatory and renal function(x2 =10.360,P =0.016),serum albumin(x2 =7.252,P =0.027),white blood cell count(x2 =7.633,P =0.022),Perforation diameter (x2 =9.770,P =0.008),Geroge grade of intraperitoneal contamination (x2 =10.086,P =0.006) were related to postoperative death (P ＜ 0.05).Multivariate analysis showed that complicating severe heart and lung diseases,preexisted circulatory and renal dysfunction,white blood cell count ＜ 4 × 109/L,size ＞ 3 cm,intraperitoneal contamination larger than one quadrant were independent risk factors for postoperative death.Conclusion Risk factors related to postoperative death of rectosigmoid junction tumor perforation were preoperative important organ dysfunction and intraperitoneal infection.

Objective To explore the effects of transitional care based on Wechat in discharged patients with intestinal stoma.Methods A total of 120 inpatients with intestinal stoma in department of stomach,intestine,colon,rectum and anus in China-Japan Union Hospital,Jilin University were recruited in 2015. They were randomly divided into observation group (n=60,routine health education on leaving hospital and transitional care through Wechat provided by members of the Wechat transitional care group for discharged patients,6 months follow-up) and control group (n=60,routine health education on leaving hospital and normally further consultation in outpatient service of stoma,6 months follow-up) according to the order of leaving hospital. The complications rate on intestinal stoma between two groups was compared at the first,third and sixth month after leaving hospital. The depression and satisfaction with nursing care was compared too at the sixth month. Results One month after leaving hospital,the incidence rates of infection in sutures around stoma and mucosa membrane separation in control group were significantly higher than those in observation group (P<0.05). Three months after leaving hospital,the incidence rates of dermatitis,infection in sutures around stoma and granuloma in control group were significantly higher than those in observation group (P<0.05). Six months after leaving hospital,the incidence rates of dermatitis and granuloma in control group were significantly higher than those in observation group (P<0.05). The score of depression in observation group was significantly lower than that in control group (P<0.05). Besides,the satisfaction with nursing care in observation group was higher than that in control group with a significant difference (P<0.05).Conclusions The transitional care based on Wechat has great significance in improving depression,reducing the incidence rates of complications on intestinal stoma and improving the satisfaction with nursing care. It is worth to be used widely.

Background and objectiveIt is so far not clear that how myasthenia gravis (MG) affected the prognosis of thymoma patients. The aim of this assay is to compare the postoperative survival between patients with thymoma only and those with both thymoma and MG.MethodsThe Chinese Alliance for Research in Thymomas (ChART) registry recruited patients with thymoma from 18 centers over the country on an intention to treat basis from 1992 to 2012. Two groups were formed according to whether the patient complicated MG. Demographic and clinical data were reviewed, Patients were fol-lowed and their survival status were analyzed.Results There were 1,850 patients included in this study, including 421 with and 1,429 without MG. Complete thymectomy were done in 91.2% patients in MG group and 71.0% in non-MG group (P<0.05). There were more percentage of patients with the histology of thymoma AB, B1, or B2 (P<0.05) in MG group, and more percentage of patients with MG were in Masaoka stage I and II. The 5 year and 10 year OS rates were both higher in MG group (93%vs 88%; 83%vs 81%,P=0.034) respectively. The survival rate was signiifcantly higher in patients with MG when the Masaoka staging was III/IV (P=0.003). Among patients with advanced stage thymoma (stage III, IVa, IVb), the constitu-ent ratios of III, IVa, IVb were similar between MG and Non-MG group. Histologically, however, there were signiifcantly more proportion of AB/B1/B2/B3 in the MG group while there were more C in the non-MG group (P=0.000). Univariate analyses for all patients showed that MG, WHO classiifcation, Masaoka stage, surgical approach, chemotherapy and radiotherapy and resectability were signiifcant factors, and multivariate analysis showed WHO Classiifcation, Masaoka stage, and resectability were strong independent prognostic indicators.ConclusionAlthough MG is not an independent prognostic factor, the sur-vival of patients with thymoma was superior when MG was present, especially in late Masaoka stage patients. Possible reasons included early diagnosis of the tumor, better histologic types, an overall higher R0 resection and less recurrence.

Background and objectiveTo compare the predictive effect of the Masaoka-Koga staging system and the International Association for the Study of Lung Cancer (IASLC)/the International Thymic Malignancies Interest Group (ITMIG) proposal for the new TNM staging on prognosis of thymic malignancies using the Chinese Alliance for Research in Thymomas (ChART) retrospective database.MethodsFrom 1992 to 2012, 2,370 patients in ChART database were ret-rospectively reviewed. Of these, 1,198 patients with complete information on TNM stage, Masaoka-Koga stage, and survival were used for analysis. Cumulative incidence of recurrence (CIR) was assessed in R0 patients. Overall survival (OS) was evalu-ated both in an R0 resected cohort, as well as in all patients (any R status). CIR and OS were ifrst analyzed according to the Masaoka-Koga staging system. Then, they were compared using the new TNM staging proposal.Results Based on Masaoka-Koga staging system, signiifcant difference was detected in CIR among all stages. However, No survival difference was revealed between stage I and II, or between stage II and III. Stage IV carried the highest risk of recurrence and worst survival. According to the new TNM staging proposal, CIR in T1a was signiifcantly lower comparing to all other T categories (P<0.05) and there is a signiifcant difference in OS between T1a and T1b (P=0.004). T4 had the worst OS comparing to all other T categories. CIR and OS were signiifcantly worse in N(+) than in N0 patients. Signiifcant difference in CIR and OS was detected between M0 and M1b, but not between M0 and M1a. OS was almost always statistically different when comparison was made between stages I-IIIa and stages IIIb-IVb. However, no statistical difference could be detected among stages IIIb to IVb.Conclusion Compared with Masaoka-Koga staging, the IASLC/ITMIG TNM staging proposal not only describes the extent of tumor invasion but also provides information on lymphatic involvement and tumor dissemination. Further study using prospectively recorded information on the proposed TNM categories would be helpful to better grouping thymic tumors for predicting prognosis and guiding clinical management.

Background and objectiveTo evaluate the role of preoperative induction therapy on prognosis of local-ly advanced thymic malignancies.MethodsBetween 1994 and 2012, patients received preoperative induction therapies (IT group) in the Chinese Alliance for Research in Thymomas (ChART) database, were compared with those having surgery di-rectly atfer preoperative evaluation (DS group). All tumors receiving induction therapies were locally advanced (clinically stage III-IV) before treatment and those turned out to be in pathological stage I and II were considered downstaged by induction. Clinical pathological characteristics were retrospectively analyzed. To more accurately study the effect of induction therapies, stage IV patients were then excluded. Only stage I-III tumors in the IT group and stage III cases in the DS group were selected for further comparison in a subgroup analysis.Results Only 68 (4%) out of 1,713 patients had induction therapies, with a R0 resection of 67.6%, 5-year recurrence of 44.9%, and 5- and 10-year overall survivals (OS) of 49.7% and 19.9%. Seventeen pa-tients (25%) were downstaged atfer induction. Signiifcantly more thymomas were downstaged than thymic carcinomas (38.7%vs 13.9%,P=0.02). Tumors downstaged atfer induction had signiifcantly higher 5-year OS than those not downstaged (93.8%vs 35.6%,P=0.013). For the subgroup analysis when stage IV patients were excluded, 5-year OS was 85.2% in the DS group and 68.1% in the IT group (P<0.001), although R0 resection were similar (76.4%vs 73.3%,P=0.63). However, 5-year OS in tumors downstaged atfer induction (93.8%) was similar to those in the DS group (85.2%,P=0.438), both signiifcantly higher than those not downstaged atfer induction (35.6%,P<0.001).ConclusionOnly 68 (4%) out of 1,713 patients had induction therapies, with a R0 resection of 67.6%, 5-year recurrence of 44.9%, and 5- and 10-year overall survivals (OS) of 49.7% and 19.9%. Seventeen patients (25%) were downstaged atfer induction. Signiifcantly more thymomas were downstaged than thy-mic carcinomas (38.7%vs 13.9%,P=0.02). Tumors downstaged atfer induction had signiifcantly higher 5-year OS than those not downstaged (93.8%vs 35.6%,P=0.013). For the subgroup analysis when stage IV patients were excluded, 5-year OS was 85.2% in the DS group and 68.1% in the IT group (P<0.001), although R0 resection were similar (76.4%vs 73.3%,P=0.63). However, 5-year OS in tumors downstaged atfer induction (93.8%) was similar to those in the DS group (85.2%,P=0.438), both signiifcantly higher than those not downstaged atfer induction (35.6%,P<0.001).

Background and objectiveVideo-assisted thoracoscopic surgery (VATS) theoretically offers advantages over open thymectomy for clinically early-stage (Masaoka-Koga stage I and II) thymic malignancies. However, longterm outcomes have not been well studied. We compared the postoperative outcomes and survival from a cohort study based on the database of the Chinese Alliance for Research in Thymomas (ChART).MethodsBetween 1994 and 2012, data of 1,117 patients hav-ing surgery for clinically early-stage (Masaoka-Koga stage I and II) tumors were enrolled for the study. Among them, 241 cases underwent VATS thymectomy (VATS group), while 876 cases underwent open thymectomy (Open group). Univariate analyses were used to compare the clinical character and perioperative outcomes between the two groups. And multivariate analysis was performed to determine the independent predictive factors for long-term survival.Results Compared with the Open group, the VATS group had higher percentage of total thymectomy (80.5%vs 73.9%,P=0.028), resection rate (98.8%vs 88.7%,P<0.001) and less recurrence (2.9%vs 16.0%,P<0.001). Five-year overall survival was 92% atfer VATS and 92% atfer open thymectomy, with no signiifcant difference between the two groups (P=0.15). However, 5-year disease free survival were 92% in VATS group and 83% in Open group (P=0.011).Cox proportional hazards model revealed that WHO classiifcation, Masaoka-Koga stage and adjuvant therapy were independent predictive factors for overall survival, while surgical approach had no signiifcant impact on long-term outcome.ConclusionhTis study suggests that VATS thymectomy is an effective approach for clinically early-stage thymic malig-nancies. And it may offer better perioperative outcomes, as well as equal oncological survival.