OBJECTIVE There are serious hazards in depression,and the precise mechanism underlying the delayed onset of clinical antidepressants remains unclear.The purpose of this study was to investigate the regular pattern of the speed-limiting role of excitation/inhibition(E/I)function balance in the mechanism of antidepressant action.METHODS Based on the previous study,we focused on glutamatergic pyramidal neurons in the medial prefrontal cortex(mPFC)here and used its excitability to represent the establishment of a new E/I functional balance.We studied the changes in the firing activity of glutamatergic pyramidal neuron in the mPFC at different administration times for five types of antidepressants that act on different pharmacological targets and different onset times,including fluoxetine(SSRI),duloxetine(SNRI),vilazodone[serotonin 1A receptor(5-HT1A)ago-nist and SSRI],ketamine[N-methyl-D-aspartate(NMDA)receptor antagonist],and hypidone hydrochloride(YL-0919,new antidepressant with sigma-1 receptor ago-nist and SSRI).We first examined the initial onset time of activation of pyramidal neurons using multichannel elec-trophysiological recordings and tested the antidepressant behavioral effects using the FST.We then selected three antidepressants(fluoxetine,ketamine,and vilazodone)to explore its effects on the BDNF-mTOR pathway by West-ern blotting.In addition,we disrupted the E/I function bal-ance using chemogenetics to investigate the antidepres-sant-like effects of YL-0919 and ketamine in the FST and TST.RESULTS We found that treatment with fluoxetine for 17 days significantly increased the firing activity of pyramidal neurons and decreased the immobility duration in the FST.Similarly,it took duloxetine for 10 d,vilazodone for 4 d,YL-0919 for 3 d and ketamine for 24 h,to exert such effects.Meanwhile,Western blotting results sug-gested that the expression of BDNF and phosphorylation of mTOR in the mPFC significantly increased.How-ever,haloperidol,a classic antipsychotic(without antide-pressant effects),exerted no such effects on the firing activities of pyramidal neurons.In addition,disrupting the E/I function balance(via activating the GABA neurons and inhibiting the glutamate neurons)blocks out the antidepressant-like effects of YL-0919 and ketamine in the FST and TST.CONCLUSION Taken together,our findings suggest that the commencement of antide-pressant effects may be accompanied by the increase in the firing activity of pyramidal neurons and the activation of the BDNF-mTOR pathway,which may be a necessary and rate-limiting process.The re-establishment of the E/I balance may be a landmark event for the onset of antide-pressant effects.

Objective:To investigate the epidemiological characteristics and current status of surgical management for esophageal cancer in China.Methods:A national database was setup through a network platform. The clinical data of esophageal cancer treated by surgery was collected from 70 major hospitals in China between January 2009 and December 2014.Results:Complete data of 8 181 cases of esophageal cancer patients who underwent surgery were recorded in the database and recruited in the analysis. Among them, 6 052 cases were male and 2 129 were female, the average age was 60.5 years.The epidemiological investigation results showed that 148 cases (1.8%) had history of psychological trauma, 7 527 cases (92.0%) were lower social economic status, 5 072 cases (62.0%) were short of fresh vegetables and fruits, 6 544 cases (80.0%) ate rough food frequently, 3 722 cases (45.5%) drank untreated water directly from lake or river or shallow well, 3 436 cases (42.0%) had a unhealthy eating habit, including habits of eating food fast (507 cases, 6.2%), eating hot food or drinking hot tea/soup (998 cases, 12.2%), eating fried food (1 939 cases, 23.7%), 4 410 cases (53.9%) had the habits of smoking cigarettes and 2 822 cases (34.5%) drank white wine frequently.The pathological results showed that 7 813 cases (95.5%) were squamous cell carcinoma, 267 cases were adenocarcinoma (3.3%), 25 cases were adenosquamous cell carcinoma (0.3%) and 50 cases were small cell carcinoma (0.6%). A total of 1 800 cases (22.0%) received preoperative neoadjuvant therapy due to locally advanced disease or difficulty of resection. The esophagectomies were performed through left thoracotomy approach in 5 870 cases (71.8%), through right chest approach in 2 215 cases (27.1%), and the remain 96 cases (1.2%) received surgery though other approaches.A total of 8 001 cases (97.8%) underwent radical resection, the other 180 cases (2.2%) received palliative resection. The 30-day postoperative mortality rate was 0.5%, the overall ≥ grade Ⅱ postoperative complication rate was 11.6% (951 cases). The 1-yr, 3-yr, and 5-yr overall actual survival rates were 82.6%, 61.6%, and 52.9%, respectively.Conclusions:The data analysis of the national database for esophageal cancer shows that bad eating habits or eating rough food without enough nutrients, lower social and economic status, drinking white wine and smoking cigarettes frequently may be correlated with tumorigenesis of esophageal cancer. However, strong evidences produced by prospective observation studies are needed. Overall, the long-term survival of esophageal cancer patients has been improved gradually due to the application of advanced surgical techniques and reasonable multimodality treatment.

Objective:To investigate the epidemiological characteristics and current status of surgical management for esophageal cancer in China.Methods:A national database was setup through a network platform. The clinical data of esophageal cancer treated by surgery was collected from 70 major hospitals in China between January 2009 and December 2014.Results:Complete data of 8 181 cases of esophageal cancer patients who underwent surgery were recorded in the database and recruited in the analysis. Among them, 6 052 cases were male and 2 129 were female, the average age was 60.5 years.The epidemiological investigation results showed that 148 cases (1.8%) had history of psychological trauma, 7 527 cases (92.0%) were lower social economic status, 5 072 cases (62.0%) were short of fresh vegetables and fruits, 6 544 cases (80.0%) ate rough food frequently, 3 722 cases (45.5%) drank untreated water directly from lake or river or shallow well, 3 436 cases (42.0%) had a unhealthy eating habit, including habits of eating food fast (507 cases, 6.2%), eating hot food or drinking hot tea/soup (998 cases, 12.2%), eating fried food (1 939 cases, 23.7%), 4 410 cases (53.9%) had the habits of smoking cigarettes and 2 822 cases (34.5%) drank white wine frequently.The pathological results showed that 7 813 cases (95.5%) were squamous cell carcinoma, 267 cases were adenocarcinoma (3.3%), 25 cases were adenosquamous cell carcinoma (0.3%) and 50 cases were small cell carcinoma (0.6%). A total of 1 800 cases (22.0%) received preoperative neoadjuvant therapy due to locally advanced disease or difficulty of resection. The esophagectomies were performed through left thoracotomy approach in 5 870 cases (71.8%), through right chest approach in 2 215 cases (27.1%), and the remain 96 cases (1.2%) received surgery though other approaches.A total of 8 001 cases (97.8%) underwent radical resection, the other 180 cases (2.2%) received palliative resection. The 30-day postoperative mortality rate was 0.5%, the overall ≥ grade Ⅱ postoperative complication rate was 11.6% (951 cases). The 1-yr, 3-yr, and 5-yr overall actual survival rates were 82.6%, 61.6%, and 52.9%, respectively.Conclusions:The data analysis of the national database for esophageal cancer shows that bad eating habits or eating rough food without enough nutrients, lower social and economic status, drinking white wine and smoking cigarettes frequently may be correlated with tumorigenesis of esophageal cancer. However, strong evidences produced by prospective observation studies are needed. Overall, the long-term survival of esophageal cancer patients has been improved gradually due to the application of advanced surgical techniques and reasonable multimodality treatment.

Objective To investigate serum total IgE levels of healthy population in two hospitals in Yantai and Weihai areas,to investigate the influencing factors of the levels of serum total IgE,which can provide information for the clinical diagnosis of allergic diseases.Methods The total serum IgE level was measured with chemiluminescence method in 1 200 cases of healthy people and 600 cases of smoking group in different age groups.Results The total IgE level of ≤6 years was (28.53±20.71)IU/mL,7-12 years was (29.74±25.94)IU/mL,13-18 years was (32±22.32)IU/mL,19-44 years was (45.2±36.27)IU/mL,45-60 years was (35.47±27.23)IU/mL,>60 years was (31.2±25.03)IU/mL.There was no effect of serum total IgE in different age groups:≤6 years,7-12 years,13-18 years,45-60 years,>60 years(t=0.610,1.508,0.777,0.160,1.518,all P>0.05),19-44 years was significantly different from other age groups(t=0.075,P<0.01).There was no gender difference of serum total IgE in different age groups (P>0.05).The total IgE level of the smoking group:19-44 years was (55.22±39.16)IU/mL,45-60 years was (42.63±28.46)IU/mL,>60 years was (39.32±26.73)IU/mL.The level of serum IgE in the smoking group was significantly higher than that in the same age group (t=0.142,0.174,0.235,all P<0.05).Conclusion No significant difference existed in healthy people of serum total IgE levels from birth to adulthood.However,the total IgE level rose when reached to 19-44 years,which then slightly declined as the growth of the age.There was no significant difference between male and female of the IgE levels in different age groups.But after the age of 19,smoking can lead to the increase of the total IgE level.

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.

Background and objectiveTo evaluate the surgical outcomes of tumor resection with or without total thymectomy for thymic epithelial tumors (TETs) using the Chinese Alliance for Research in Thymomas (ChART) retrospec-tive database.Methods Patients without preoperative therapy, who underwent surgery for early-stage (Masaoka-Koga stage I and II) tumors, were enrolled for the study. They were divided into thymectomy and thymomectomy groups according to the resection extent of the thymus. Demographic and surgical outcomes were compared between the two patients groups. Results A total of 1,047 patients were enrolled, with 796 cases in the thymectomy group and 251 cases in the thymomec-tomy group. Improvement rate of myasthenia gravis (MG) was higher atfer thymectomy than atfer thymomectomy (91.6%vs 50.0%,P<0.001). Ten-year overall survival was similar between the two groups (90.9% atfer thymectomy and 89.4% atfer thymomectomy,P=0.732). Overall, recurrence rate was 3.1% atfer thymectomy and 5.4% atfer thymomectomy, with no sig-niifcant difference between the two groups (P=0.149). Stratiifed analysis revealed no signiifcant difference in recurrence rates in Masaoka-Koga stage I tumors (3.2%vs 1.4%,P=0.259). However in patients with Masaoka-Koga stage II tumors, recurrence was signiifcantly less atfer thymectomy group than atfer thymomectomy (2.9%vs 14.5%,P=0.001).Conclusion hTymectomy, instead of tumor resection alone, should still be recommended as the surgical standard for thymic malignancies, especially for stage II tumors and those with concomitant MG.

Background and objectivePostoperative radiotherapy (PORT) for thymic tumor is still controversial. The object of the study is to evaluate the role of PORT for stage I/II/III thymic tumor.MethodsThe database of Chinese Al-liance of Research for Thymomas (ChART) was retrieved for patients with stage I/II/III thymic tumor who underwent surgi-cal therapy without neoajuvant therapy between 1994 and 2012. Univariate and multivariate survival analyses were performed. Cox proportional hazard model was used to determine the hazard ratio for death.Results 1,546 stage I/II/III patients were identiifed from ChART database. Among these patients, 649 (41.98%) underwent PORT. PORT was associated with gender, histologic type (World Health Organization, WHO), surgical extent, complete resection, Masaoka stage and adjuvant che-motherapy. The 5-yr and 10-yr overall survival (OS) rates and disease-free survival (DFS) rate for patients underwent surgery followed by PORT were 90% and 80%, 81% and 63%, comparing with 96% and 95%, 92% and 90% for patients underwent surgery alone (P=0.001,P<0.001) respectively. In univariate analysis, age, histologic type (WHO), Masaoka stage, complete-ness of resection, and PORT were associated with OS. Multivariable analysis showed that histologic type (WHO)(P=0.001), Masaoka stage (P=0.029) and completeness of resection (P=0.003) were independently prognostic factors of OS. In univari-ate analysis, gender, myasthenia gravis, histologic type (WHO), Masaoka stage, surgical approach, PORT and completeness of resection were associated with DFS. Multivariable analysis showed that histologic type (WHO) (P<0.001), Masaoka stage (P=0.005) and completeness of resection (P=0.006) were independently prognostic factors of DFS. Subgroup analysis showed that patients with incomplete resection underwent PORT achieved the better OS and DFS (P=0.010, 0.017, respectively). However, patients with complete resection underwent PORT had the worse OS and DFS (P<0.001,P<0.001, respectively). ConclusionThe current retrospective study indicated that PORT atfer incomplete resection could improve OS and DFS for patients with stage I/II/III thymic tumor. But for those atfer complete resection, PORT may not help improve prognosis on the whole.