Depressive disorder ranks as a major bur-den of disease worldwide,yet the current antidepressant medications are limited by frequent non-responsiveness and significant side effects.The lateral septum(LS)is thought to control of depression,however,the cellular and circuit substrates are largely unknown.Here,we identified a subpopulation of LS GABAergic adenosine A2A receptors(A2AR)-positive neurons mediating depres-sive symptoms via direct projects to the lateral habenula(LHb)and the dorsomedial hypothalamus(DMH).Activa-tion of A2AR in the LS augmented the spiking frequency of A2AR-positive neurons leading to a decreased activation of surrounding neurons and the bi-directional manipula-tion of LS-A2AR activity demonstrated that LS-A2ARs are necessary and sufficient to trigger depressive pheno-types.Thus,the optogenetic modulation(stimulation or inhibition)of LS-A2AR-positive neuronal activity or LS-A2AR-positive neurons projection terminals to the LHb or DMH,phenocopied depressive behaviors.Moreover,A2AR are upregulated in the LS in two male mouse mod-els of repeated stress-induced depression.This identifica-tion that aberrantly increased A2AR signaling in the LS is a critical upstream regulator of repeated stress-induced depressive-like behaviors provides a neurophysiological and circuit-based justification of the antidepressant poten-tial of A2AR antagonists,prompting their clinical transla-tion.

Objective:To understand the development of extracurricular activities among students majoring in preventive medicine in a medical college and explore the impact of perception of extracurricular activities on major courses and extracurricular performances.Methods:A self-made questionnaire on the extracurricular perception was conducted, involving such aspects as organizational support, teacher guidance, student participation, etc. In August 2019, all senior students from Department of Preventive Medicine of a medical college were investigated by the questionnaire. At the same time, we had the extracurricular performances of the students from the Communist Youth League Committee and the major courses performances from the Academic Affairs Section of the Department. The Pearson test was conducted on the dimensions and total score of extracurricular perception, extracurricular performance and major courses performance to verify the impact of extracurricular perception on major courses and extracurricular performances. SPSS 19.0 was used for normality test, chi-square test and correlation analysis.Results:A total of 95 valid questionnaires were distributed and collected. It was noted that the total score of students' extracurricular perception was higher (66.23 points), among which, the highest score of teacher guidance was 73.10, while the lowest score of students' participation was 61.85. Extracurricular perception had a significant impact on major courses and extracurricular activities, especially in organizational support and teacher's guidance.Conclusion:Teachers play an important role in extracurricular activities, and students' participation is influenced by students and school factors. It is suggested that the school should pay attention to extracurricular activities in the process of cultivating college students, education environment should be optimized, funds should be guaranteed, the extracurricular courses should be improved, and the management system should be improved. For the teachers, teachers' professional level should be improved. Teachers should provide helpful guidance for students. At the same time, teachers should learn to use new technologies to build a better environment for students' learning. In addition, teachers should provide students with opportunities to be involved in extracurricular activities and create platforms. Finally, students should actively participate in all kinds of activities both inside and outside the school.

Objective:To analyze students' learning behavior in the teaching practice of the presentation-assimilation-discussion (PAD) class based on Xuexitong platform.Methods:The PAD class based on Xuexitong platform was applied to the course of child and adolescent health in the specialty of preventive medicine. And the data were collected from the platform to analyze students' learning behavior, including the number of visits and its rules, the completion rate and duration of homework submission, the completion rate of task points, and the number of students participating in discussions. Questionnaires were used to investigate students' evaluation of the learning effect. SPSS 17.0 was used for Mann-Whitney U test, Kruskal Wallis H, and Chi-square test. Results:A total of 99 students visited the platform 40 322 times over 84 days, with a peak on the day of the discussion class, with the highest number of visits from 16:00 to 20:00, and 29.3% (29/99) of them visited the platform for less than 40 days. The completion rate of homework submission was 98.0% (582/594), with 31.1% (181/582) of the person-times less than 6 hours of homework submission duration. The completion rate of task points was 99.0% (3 919/3 960), and the number of students participating in discussions was 3 (2,7). In total, 86.9% to 90.9% of the students thought that the five aspects of learning effect were partly or basically achieved.Conclusion:Students' learning behavior is good on the whole, but their participation in discussion is few, and some of them learn passively, which needs to be further improved.

Objective:To investigate the clinical efficacy of induced membrane technique in the staged treatment of adult chronic hematogenous osteomyelitis (CHOM) of long bone.Methods:The clinical data were retrospectively analyzed of the 22 adult patients with CHOM of long bone who had been admitted to the 920th Hospital, Joint Logistics Support Force of PLA from January 2016 to December 2019. There were 18 males and 4 females, aged from 16 to 56 years (average, 31.81 years). Their disease duration ranged from 0.6 to 42.0 years, averaging 18.4 years. By the Cierny-Mader anatomical classification, 4 cases were type Ⅰ, 6 cases Type Ⅲ, and 12 cases type Ⅳ. In the first stage, the bone defects were filled with antibiotic bone cement after thorough debridement. In the second stage when the infection had been controlled, the bone defects were repaired with bone grafts after removal of the bone cement. Bone healing time and complications were followed up. The treatment effects were evaluated by comparisons of the infection control indexes [including clinical manifestations like local redness, swelling, pus, and pain, and blood white blood cell count, C-Reactive protein (CRP), and erythrocyte sedimentation rate (ESR) as well] before the primary surgery, before the secondary surgery and at the last follow-up.Results:The volumes of the bone defects after stage-one debridement ranged from 54 cm 3 to 176 cm 3 (mean, 90.9 cm 3). All patients were followed up for 20 to 51 months (mean, 30.1 months) after surgery. All bone defects healed after 4 to 11 months (mean, 6.6 months). Postoperatively, infection developed at the bone extraction site of the posterior superior iliac spine in 3 cases and pain was observed at the donor site in one case, but the conditions were relieved after symptomatic treatment. Fracture and plate breakage occurred at the bone defect site in one case who had fallen down 7 months after operation, but responded to reoperation. The last follow-up revealed such symptoms as redness, swelling and pus discharge in none of the patients. The white blood cell count [(5.70 ± 1.57) × 10 9/L and (5.65 ± 1.58) × 10 9/L], CRP [(7.56 ± 2.57) mg/L and (7.25 ± 3.83) mg/L] and ESR [(9.64 ± 2.90) mm/h and (10.55 ± 5.23) mm/h] before the secondary surgery and at the last follow-up were significantly lower than those before the primary surgery [(8.24 ± 2.18) × 10 9/L, (49.54 ± 19.56) mg/L, and (42.68 ± 13.77) mm/h] (all P < 0.05). However, there were no significant differences between the indexes before the secondary surgery and at the last follow-up ( P > 0.05). Conclusion:In the staged treatment of adult CHOM of long bone, the induced membrane technique can effectively control infection, achieve repair of bone defects, and reduce complications.

Objective To investigate the clinical efficacy and prognostic factors of autologous hematopoietic stem cell transplantation (ASCT) for Hodgkin's lymphoma (HL). Methods We retrospectively analyzed the data of 38 patients with HL who underwent ASCT. Kaplan-Meier and Cox methods were used to analyze the curative effect and prognostic factors after transplantation. Results All 38 transplanted patients obtained hematopoietic reconstitution. The CR rates before and after transplantation were 55.3% and 81.6%, respectively, and the 5-year PFS and OS were 76.1% and 79.0%, respectively. Univariate analysis showed that B symptoms, IPS score, pre-transplant remission status, extranodal invasion, and pretreatment regimen were the factors affecting the prognosis of ASCT in patients with HL. Multivariate analysis showed that B symptom was an independent risk factor affecting 5-year PFS. Conclusion ASCT is effective in the treatment of high-risk, relapsed, and refractory patients with HL. B symptom is an independent risk factor affecting the prognosis of transplantation.

The WHO Classification of Thoracic Tumors (5 th edition) mainly has the following changes in the chapter of pleural malignant mesothelioma. (1) The concept of mesothelioma in situ and its diagnostic method have been established for the first time; (2) The tumour grading of pleural malignant mesothelioma was added, it was divided into low grade and high grade according to the cellular atypia, mitotic activity and presence of necrosis. (3) The morphological features of pleural malignant mesothelioma was classified into architectural pattern, cellular and stromal features, the correlation between histological features and prognosis was refined, and some of the controversial cellular types have been reclassified. In this review, we introduced the changes of related pathologic diagnosis, in the WHO Classification of Thoracic Tumors (5 th edition) and discussed its clinical significance.

The WHO Classification of Thoracic Tumors (5 th edition) mainly has the following changes in the chapter of pleural malignant mesothelioma. (1) The concept of mesothelioma in situ and its diagnostic method have been established for the first time; (2) The tumour grading of pleural malignant mesothelioma was added, it was divided into low grade and high grade according to the cellular atypia, mitotic activity and presence of necrosis. (3) The morphological features of pleural malignant mesothelioma was classified into architectural pattern, cellular and stromal features, the correlation between histological features and prognosis was refined, and some of the controversial cellular types have been reclassified. In this review, we introduced the changes of related pathologic diagnosis, in the WHO Classification of Thoracic Tumors (5 th edition) and discussed its clinical significance.

Objective:To investigate the clinical effect of induced membrane technique combined with staged internal fixation for treatment of infected femoral nonunion.Methods:A retrospective case series study was conducted to analyze the clinical data of 21 patients with infected femoral nonunion treated from January 2016 to December 2018 in 920th Hospital of Joint Logistics Support Force of PLA. There were 13 males and 8 females, with the age of 18-57 years [(38.9±6.7)years]. The duration of nonunion was 7-78 months [(27.1±11.4)months]. All patients were treated by induced membrane technique in two stages. At stage I, the original internal fixation was removed and debrided thoroughly, then the antibiotic-loaded bone cement and locking compression plate (LCP) were placed. The length of bone defect following debridement was 5-15 cm[(7.4±1.9)cm]. At stage II, the bone defect was reconstructed with bone grafts and fixed with the intramedullary nail and/or LCP. The wound condition, white blood cell count, C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) were recorded after stage I surgery and at the last follow-up to measure infection control. The complications and bone healing time were recorded. The bone healing was evaluated by the Paley criteria and the functional recovery of the affected limb was evaluated by the range of motion of the knee at the last follow-up.Results:All patients were followed up for 23-43 months [(31.9±6.7)months]. The infection recurred in 4 patients after stage I surgery, and the wound healed after repeated debridement. There was no infection recurrence after stage II surgery. The white blood cell count, CRP and ESR were (6.1±1.8)×10 9/L, (10.1±3.1)mg/L, (10.2±3.4)mm/h at the last follow-up, significantly decreased from preoperative (15.0±4.8)×10 9/L, (69.8±14.8)mg/L, (66.2±13.2)mm/h ( P<0.05). The incidence of complications was 43%. Besides infection recurrence in 4 patients after stage I surgery, the donor site at the posterior superior iliac spine in 3 patients showed delayed healing, and the limb shortening occurred in 2 patients with the discrepancy of 3 cm and 4 cm. Bony union was observed in all patients within 6-16 months [(8.8±2.7)months]. The results were excellent in 19 patients and good in 2 patients according to the Paley criteria at the last follow-up. The knee range of motion was significantly improved from preoperative 30.0°(15.0°, 110.0°) to 90.0°(61.5°, 120.0°) at the last follow-up ( P<0.05). Conclusion:For infected femoral nonunion, the induced membrane technique combined with staged internal fixation can effectively control infection, achieve bony union, and promote functional recovery.

Objective:To study the changes of food characters in early swallowing recovery in patients with different laryngeal function preservation surgery.Methods:Collected patients with laryngeal cancer hypopharyngeal cancer who underwent laryngeal function preservation surgery in Lihuili Hospital of Ningbo Medical Center from January 2019 to March 2020. By fiberoptic endoscopic evaluation of swallowing (FEES) combined with Penetration and Aspiration Scale (PAS), prospectively observed the aspiration and invasion of solid, paste, fluid and other food in the early stage of trial feeding in patients with laryngeal hypopharyngeal cancer undergoing open laryngeal function preservation.Results:Among the 69 patients, 21 had vertical partial laryngectomy and 19 had partial pharyngeal partial laryngectomy. 15 days after the operation, 2 groups of patients after solid and paste food adaptability scored (1.14±0.36), (1.29±0.56) and (2.53±2.04), (2.84±2.31) points, Friedman Mtest for comparison difference had statistical significance ( Mvalues were 23.463 and 22.227, P<0.01); the liquid food for adaptability scored (2.10±1.09), (4.42±2.24) points, the pairwise comparison of liquid, solid and paste showed statistically significant differences ( tvalues were-0.976 to 1.105, P<0.05). The pairwise comparison of the adaptability of the two groups on 20 days after surgery showed no statistically significant difference ( P>0.05).Throat on the cricoid cartilage resection-ring hyoid epiglottis anastomosis (SLCP-CHEP) was 17 cases, laryngeal glottis level partial resection was 12 cases; postoperative 15 days the adaptability on the behavior of three kinds of food grade 2 groups of patients (4.65±1.90), (5.59±1.46), (6.53±1.13) points and (6.67±1.07), (4.50±2.07), (6.92±0.79) points, respectively; Minspection differences were statistically significant ( Mvalues were 29.525, 22.136, P<0.01).The pairwise comparison of solid and paste food in the two groups 20 days after the operation showed no statistically significant difference ( P>0.05), while the difference of liquid and paste was statistically significant ( tvalues were-1.375 to-0.853, P<0.05). Conclusion:In the early recovery of patients undergoing laryngeal function preservation surgery, the vertical group and the partial pharyngeal partial laryngectomy group has better adaptability to solid and paste food. The horizontal group has better adaptability to paste, the CHEP group has better adaptability to solid, and the four groups has the worst adaptability to convection, the recovery time of convective mass between the CHEP group and the horizontal group was longer. To understand the adaptability of patients with different surgical methods to food traits at the early stage of trial feeding can help to implement targeted rehabilitation programs, carry out progressive diet training, and reduce the complications of misinvasion, aspiration, aspiration pneumonia and other complications in the recovery cycle.

OBJECTIVE：To establish a method for concentration determination of anlotinib in human plasma and apply it in the clinic. METHODS ：The plasma samples were pretreated by salting-out assisted with liquid-liquid extraction with ammonium acetate as salting out assistant and acetonitrile as solvent. Using voriconazole as internal standard ，LC-MS/MS method was adopted. The separation was performed on Waters X Bridge C 18 column with mobile phase consisting of 0.2％ formic acid solution- acetonitrile（gradient elution ）at the flow rate of 1 mL/min. The column temperature was set at 40 ℃，and sample size was 10 μL. The split ratio was 3∶7. The electrospray ion source and multiple reaction monitoring mode were used for the analysis. The ion pair of anlotinib and internal standard under positive ion mode were m/z 408.3→339.3 and m/z 350.2→281.3，respectively. RESULTS ： Anlotinib showed a good linear relationship in the concentration range of 0.2-200 ng/mL（R2＞0.996 7）. The lowest limit of quantitation was 0.2 ng/mL. Intra-day and inter-day RSDs were no more than 12％ （n＝6 or n＝3）. Accuracies were 90.92％-108.00％（n＝6 or n＝3）. The average extraction recoveries were 87.51％-100.00％（RSD＜8％，n＝6）. The average matrix effects were 96.66％-99.93％（RSD＜5％，n＝6）. The plasma concentration of 3 patients with NSCLC treated with anlotinib was 8.74-65.60 ng/mL. CONCLUSIONS ：The method is simple ，accurate and specific ，and is suitable for the plasma concentration monitoring of anlotinib in NSCLC patients.