Anxiety disorder is a major symptom of autism spectrum disorder (ASD) with a comorbidity rate of ~40%. However, the neural mechanisms of the emergence of anxiety in ASD remain unclear. In our study, we found that hyperactivity of basolateral amygdala (BLA) pyramidal neurons (PNs) in Shank3 InsG3680 knock-in (InsG3680^+/+) mice is involved in the development of anxiety. Electrophysiological results also showed increased excitatory input and decreased inhibitory input in BLA PNs. Chemogenetic inhibition of the excitability of PNs in the BLA rescued the anxiety phenotype of InsG3680^+/+ mice. Further study found that the diminished control of the BLA by medial prefrontal cortex (mPFC) and optogenetic activation of the mPFC-BLA pathway also had a rescue effect, which increased the feedforward inhibition of the BLA. Taken together, our results suggest that hyperactivity of the BLA and alteration of the mPFC-BLA circuitry are involved in anxiety in InsG3680^+/+ mice.
Animals ; Prefrontal Cortex/metabolism* ; Basolateral Nuclear Complex/metabolism* ; Mice ; Anxiety/metabolism* ; Nerve Tissue Proteins/genetics* ; Male ; Gene Knock-In Techniques ; Pyramidal Cells/physiology* ; Mice, Transgenic ; Neural Pathways/physiopathology* ; Mice, Inbred C57BL ; Microfilament Proteins

Hepatic fibrosis is a key intermediate stage in the progression of various chronic liver diseases to liver cirrhosis and liver cancer. Traditional Chinese medicine （TCM） has a good effect in the treatment of hepatic fibrosis， but its mechanism of action remains unclear. This article introduces the pathological mechanisms of hepatic fibrosis， including etiology and pathogenesis based on TCM theory and related mechanisms in Western medicine （such as hepatic stellate cell ［HSC］ activation， hepatic fibrosis driven by metabolic reprogramming， and key signaling pathways in hepatic fibrosis）. On this basis， this article analyzes the core mechanisms of TCM in the treatment of hepatic fibrosis， including inhibiting HSC activation and proliferation， suppressing liver inflammation and modulating immunity， counteracting lipid peroxidation damage， regulating the synthesis and secretion of pro-fibrotic factors， maintaining the metabolic balance of extracellular matrix， regulating key signaling pathways， modulating gut microbiota， and inhibiting sinusoidal capillarization， in order to summarize the mechanism of action of TCM in the treatment of hepatic fibrosis and lay a foundation for better developing TCM-based therapeutics for hepatic fibrosis.

【Objective】 To analyze the literature on the relationship between gut microbiota and bone metabolism, identify the current research hotspots and difficulties, and provide research ideas and directions for the clinical prevention and treatment of bone metabolism related diseases. 【Methods】 Based on the Citespace literature visualization analysis software, the co-occurrence and cluster analysis of keywords and other information of the included 394 literatures were performed, and the visual map was drawn. 【Results】 Among the included literatures, the keywords such as inflammatory bowel disease, T cells, dendritic cells, short-chain fatty acids, and chronic kidney disease appeared with high frequency. The cluster of intestinal alkaline phosphatase, metabolic osteoarthritis, dendritic cells, and signaling pathway was the current research hotspot. Recent years have witnessed a rapid increase in published articles in this field, with the United States as the leading origin. 【Conclusion】 The mechanism by which gut microbiota interferes with the immune system and regulates bone metabolism to maintain bone homeostasis is still the core of current research.

ObjectiveTo investigate the characteristics of polysomnography （PSG） in depression patients complicating moderate-to-severe obstructive sleep apnea hypopnea syndrome （OSAHS）. MethodsA retrospective analysis was conducted on the outpatients， inpatients and physical examination population who completed overnight PSG monitoring in the sleep medicine center of Suzhou Guangji Hospital from December 2017 to October 2019. Four groups of subjects were finally enrolled， including depression patients with moderate-to-severe OSAHS （n=31）， depression patients without OSAHS （n=79）， moderate-to-severe OSAHS patients （n=96） and normal control group （n=32）. The sleep process related indicators （total sleep time， sleep latency， number of awakenings）， sleep structure related indicators （N1， N2， N3， percentage of REM sleep， REM latency， REM sleep duration）， sleep-related respiratory variables （oxygen reduction index） and other polysomnographic parameters of the four groups were compared. ResultsIn terms of sleep process， the total sleep time， sleep latency and number of awakenings yielded significant differences among the four groups （F=2.874， 3.959， 12.291， P<0.05 or 0.01）. In terms of sleep structure， the percentage of total sleep time in N2 and N3 stages demonstrated significant differences among the four groups （F=13.885， 48.013， P<0.01）. The REM latency， REM sleep duration and percentage of REM sleep manifested significant differences among the four groups （F=41.492， 11.827， 10.552， P<0.01）. In terms of sleep-related respiratory variables， the oxygen reduction index exhibited significant differences among the four groups （F=170.585， P<0.05）. ConclusionDepression patients complicating moderate-to-severe OSAHS suffer from severe sleep process and structural disturbances， accompanied by quite frequent and severe sleep-related respiratory events.

Objective: To study influencing factors which cause the endometrial diseases in patients with breast cancer after operation. Methods: A retrospective study was performed on 212 breast cancer post-operation patients with endometrial diseases between June 2006 and January 2018 in Women’s Hospital School of Medicine Zhejiang University to analyse the factors which influenced the endometrial diseases. Results: The abnormal uterine bleeding and endometrial thickness were related to the severity of endometrial disease in patients with breast cancer, and they were independent risk factors for breast cancer patients to have endometrial cancer (P<0.05) . When the diagnostic cut off value of endometrial thickness was ≥0.49 cm, the sensitivity and specificity to endometrial cancer were 78% and 25%, respectively. The average endometrial thickness was (0.56±0.39) cm in patients who were treated by selective estrogen receptor modulator (SERM) after gynecological surgery, which was significantly thicker than that of aromatase inhibitor (AI) group [ (0.33±0.23) cm] and no treatment group [ (0.44±0.28) cm, P<0.05]. The endometrial disease recurrent rate and reoperation rate in SERM group were (26.2%, 14.3%) slightly higher than that of AI group (9.5%, 4.8%) and no treatment group (21.6%, 4.9%), but there were not significant differences (all P>0.05). Conclusions The clinical symptom of abnormal uterine bleeding and thickening endometrium are risk factors for breast cancer patients to have endometrial cancer. The endometrial thickness has high predictive value for breast cancer patients to diagnose endometrial cancer. The SERM treatment increases the endometrial thickness, recurrent rate and reoperation rate in post-operation patients.

OBJECTIVE: To investigate the evaluation value of preoperative peripheral blood lymphocyte-to-monocyte ratio (LMR) on the prognosis of patients with stage III colon cancer undergoing radical resection and postoperative adjuvant chemotherapy. METHODS: Electronic medical record were retrospectively retrived for stage III colon cancer patients who underwent radical surgery at Sun Yat-sen University Cancer Center from December 2007 to December 2013. Inclusion criteria were pathologically comfirmed colon adenocarcinoma, complete clinicopathological data, and postoperative XELOX (oxaliplatin + capecitabine) chemotherapy with follow-up of at least 3 months. Patients with neoadjuvant anti-tumor therapy, infectious disease, other malignant tumors and death of non-tumor causes within 3 months after operation were excluded. A total of 258 patients were included in this retrospective cohort study, including 146 males and 112 females with median age of 55 (22 to 85) years. Tumors of 100(38.8%) patients were located in the right hemicolon, and of 158 (61.2%) in the left hemicolon. Tumors of 194(75.2%) patients were highly and moderately differentiated, and of 64 (24.8%) were poorly differentiated. According to the TNM tumor pathological stage of AJCC 7th edition, 196 (76.0%) patients were stage IIIA to IIIB, and 62(24.0%) patients were stage IIIC. The median preoperative CEA was 3.8 (0.3 to 287.5) μg /L and the median cycle of the adjuvant chemotherapy was 6 (1 to 8). The cut-off value of preoperative LMR in prediction of 3-year overall survival (OS) outcome was determined by receiver operating characteristic (ROC) curve analysis. All patients were divided into low LMR group and high LMR group according to the critical value. Clinicopathological characteristics between the two groups were compared by using chi-square test or Fisher's exact test as appropriate. The 3-year disease-free survival and overall survival rate were estimated with the Kaplan-Meier method, and differences between two groups were assessed with the log-rank test. Univariate and multivariate analyses were performed through Cox regression model. RESULTS: ROC curve showed that the cut-off value of preoperative LMR in predicting 3-year overall survival was 4.29. Then 143 patients were divided into low LMR group (LMR<4.29) and 115 patients into high LMR group (LMR ≥ 4.29). Compared with high LMR group, the low LMR group presented higher proportions of male [62.2%(89/143) vs. 50.4%(58/115), χ²=4.167, P=0.041], right hemicolon cancer [44.8% (64/143) vs. 31.3% (36/115), χ²=4.858, P=0.028], and the largest tumor diameter>4 cm [60.1% (86/143) vs. 33.0% (38/115), χ²=18.748, P<0.001]. During a median follow-up of 46.0 (range, 3.0 to 74.0) months, 3-year disease-free survival rate was 83.8% in high LMR group and 78.9% in low LMR group, which was not significantly different (P=0.210). While 3-year overall survival rate in low LMR group was significant lower than that in high LMR group (86.6% vs. 97.2%, P=0.018). Univariate analysis revealed that preoperative low LMR (HR=2.841, 95%CI: 1.146 to 7.043, P=0.024), right hemicolon cancer (HR=2.865, 95%CI: 1.312 to 6.258, P=0.008) and postoperative adjuvant chemotherapy≥6 cycles (HR=0.420, 95%CI: 0.188 to 0.935, P=0.034) were the risk factors for poor overall survival. Multivariate analysis identified that preoperative low LMR (HR=2.550, 95%CI: 1.024 to 6.347, P=0.004) and right hemicolon cancer (HR=2.611, 95%CI: 1.191 to 5.723, P=0.017) were the independent risk factors for overall survival. CONCLUSIONS Preoperative peripheral blood LMR level represents an effective prognostic predictor for patients with stage III colon cancer receiving radical therapy. Low LMR indicates the poor prognosis and such patients require aggressive postoperative treatment strategy.
Adenocarcinoma ; blood ; drug therapy ; surgery ; Adult ; Aged ; Aged, 80 and over ; Antineoplastic Combined Chemotherapy Protocols ; administration & dosage ; Chemotherapy, Adjuvant ; Colonic Neoplasms ; blood ; drug therapy ; surgery ; therapy ; Female ; Humans ; Kaplan-Meier Estimate ; Leukocyte Count ; methods ; Lymphocytes ; Male ; Middle Aged ; Monocytes ; Preoperative Care ; Prognosis ; Retrospective Studies ; Young Adult

Chimeric antigen receptor (CAR) T lymphocyte has shown attractive prospects in the treatment of lymphohematopoietic malignancies including B-cell lymphoblastic leukemia, B-cell lymphoma and multiple myeloma. Many applicants have submitted investigational new drug (IND) applications to Center for Drug Evaluation of National Medical Products Ggency, however, many of the INDs have problems in patient selection, prognostic indicators and risk management, etc, which might hinder the evaluation of the safety and efficacy of CAR-T cells. Thus, we made some suggestions on the above-mentioned problems through summarizing clinical experience and communicating with domestic clinical experts, which the sponsors and researchers can refer to when conducting CAR-T cell clinical trials for registration.

Objective To study influencing factors which cause the endometrial diseases in patients with breast cancer after operation. Methods A retrospective study was performed on 212 breast cancer post-operation patients with endometrial diseases between June 2006 and January 2018 in Women's Hospital School of Medicine Zhejiang University to analyse the factors which influenced the endometrial diseases. Results The abnormal uterine bleeding and endometrial thickness were related to the severity of endometrial disease in patients with breast cancer, and they were independent risk factors for breast cancer patients to have endometrial cancer (P<0.05). When the diagnostic cut off value of endometrial thickness was ≥0.49 cm, the sensitivity and specificity to endometrial cancer were 78% and 25%, respectively. The average endometrial thickness was (0.56 ± 0.39) cm in patients who were treated by selective estrogen receptor modulator (SERM) after gynecological surgery, which was significantly thicker than that of aromatase inhibitor (AI) group [(0.33 ± 0.23) cm] and no treatment group [(0.44 ± 0.28) cm, P<0.05]. The endometrial disease recurrent rate and reoperation rate in SERM group were (26.2%, 14.3%) slightly higher than that of AI group (9.5%, 4.8%) and no treatment group (21.6%, 4.9%), but there were not significant differences (all P>0.05). Conclusions The clinical symptom of abnormal uterine bleeding and thickening endometrium are risk factors for breast cancer patients to have endometrial cancer. The endometrial thickness has high predictive value for breast cancer patients to diagnose endometrial cancer. The SERM treatment increases the endometrial thickness, recurrent rate and reoperation rate in post-operation patients.

Objective To explore the value of KRAS mutation predicting prognosis of patients with colorectal liver-only metastasis after hepatectomy.Methods The retrospective case-control study was conducted.The clinicopathological data of 79 patients with colorectal liver-only metastasis who underwent hepatectomy in the Sun Yat-sen University Cancer Center between October 2010 and October 2016 were collected.KRAS mutation in colorectal cancer tissue was detected by fluorescent quantitative polymerase chain reaction (PCR) and laser flight mass spectrometer.Observation indicators:(1) KRAS mutation;(2) relationship between KRAS mutation and clinicopathological factors of patients with colorectal liver-only metastasis;(3) follow-up and survival situations.Follow-up using outpatient examination and telephone interview was performed to detect recurrence-free survival and overall survival up to June 30,2017.The relationship between KRAS mutation and clinicopathological factors of patients with colorectal liver-only metastasis was analyzed by the chi-square test or Fisher exact probability.The survival curve and time were respectively drawn and calculated by the Kaplan-Meier method,and COX regression model was used for survival analysis.Results (1) KRAS mutation:79 patients received KRAS gene detection of surgical tumor tissues,including 54 in wide-type mutation and 25 in mutant-type mutation.Of 25 patients in mutant-type mutation,mutation at codon 12 of KRAS exon 2 was in 21 patients,and GGT＞GAT (G12D),GGT＞GTT (G12V),GGT＞TGT (G12C),GGT＞GCT (G12A) and GGT＞CGT (G12R) of mutation types were respectively detected in 13,4,2,1 and 1 patients;mutation at codon 13 of KRAS exon 2 was in 3 patients,with a mutation type of GGC＞GAC (G13D);mutation at codon 61 of KRAS exon 3 was in 1 patient,with a mutation type of CAA＞CAT (Q61H).(2) Relationship between KRAS mutation and clinicopathological factors of patients with colorectal liver-only metastasis:primary tumor located in right and left hemicolon were detected in 11,14 patients with mutant-type mutation and 7,47 patients with wide-type mutation,respectively,with a statistically significant difference (x2=9.357,P＜0.05).(3) Follow-up and survival situations:79 patients were followed up for 2.0-71.0 months,with a median time of 29.0 months.Median recurrence-free survival time and median overall survival time were respectively 11.3 months,43.5 months in patients with mutant-type mutation and 9.9 months,44.3 months in patients with wide-type mutation,respectively,with no statistically significant difference in recurrence-free and overall survivals [hazard ratio (HR)=1.255,1.108,95％ confidence interval (CI):0.741-2.126,0.521-2.355,P＞0.05].Further analysis:of patients with low clinical risk score (CRS) of Memorial Sloan Caitlin Cancer Center (MSKCC),median recurrence-free survival time was 11.3 months in 17 patients with mutant-type mutation and 23.5 months in 26 patients with wide-type mutation,with a statistically significant difference in recurrence-free survival of patients (HR=2.082,95％CI:1.006-4.307,P＜0.05).The median overall survival time was 44.6 months in 17 patients with mutant-type mutation and 49.0 months in 26 patients with wide-type mutation,with no statistically significant difference in overall survival of patients (HR =1.165,95％CI:0.413-3.282,P＞0.05).Of patients with high CRS of MSKCC,median recurrence-free survival time and median overall survival time were respectively 5.6 months,28.7 months in 7 patients with mutant-type mutation and 4.5 months,36.7 months in 24 patients with wide-type mutation,with no statistically significant difference in recurrence-free and overall survivals (HR=0.402,1.197,95％CI:0.284-1.656,0.371-3.866,P＞0.05).Conclusions KRAS mutation is often detected in patients with right colon cancer.Recurrence-free survival time is obviously reduced in patients with KRAS mutation and low CRS of MSKCC.

Objective To investigate the clinical outcome of pancreatic pseudocyst(PPC)treated with non-surgical methods,and to compare the efficacy and safety between percutaneous drainage and endoscopic drainage in the management of PPC.Methods From February 2010 to July 2017,clinical data of patients with PPC,who received percutaneous drainage or endoscopic drainage,were retrospectively analyzed.The symptom relief rate,short-term and long-term radiologic remission rate,complication rate, recurrence rate and length of hospital stay were compared between patients treated by ultrasound guided percutaneous drainage(percutaneous group),by endoscopic ultrasonography-guided drainage(EUS group)and by endoscopic retrograde pancreatography guided transpapillary drainage(ERP group).Two independent samples t test,one-way analysis of variance,non-parametric test and Fisher′s exact test were performed for statistical analysis.Results A total of 153 patients were treated and the operation was successfully conducted in 148 patients(96.7%),of whom 39 were in percutaneous group,73 in EUS group and 36 in ERP group.The median follow-up time was 26 weeks(two weeks to 358 weeks).The symptom relief rate,long-term radiographic remission rate,complication rate,recurrence rate and retreatment rate of percutaneous group,EUS group and ERP group were 87.2%(34/39),79.5%(58/73),80.6%(29/36);81.5%(22/27),88.6%(39/44),66.7%(16/24);17.9%(7/39),28.8%(21/73),16.7%(6/36);15.0%(3/20),13.8%(8/58),10.0%(2/20);and 10.3%(4/39),8.2%(6/73),2.8%(1/36),respectively.There was no statistically significant difference among three groups (all P> 0.05).The short-term radiographic remission rate of ERP group was significantly lower than those of percutaneous group and EUS group(46.7%,14/30 vs 77.1%,27/35 and 87.7%,64/73),and the differences were statistically significant(χ2 =6.442 and 19.450,both P<0.01).The median hospital stay of percutaneous group was longer than those of EUS group and ERP group(14.0 days vs 9.0 days and 8.0 days),and the differences were statistically significant(Z= -3.687 and -2.630,both P<0.01).Conclusions The efficacies of percutaneous drainage and EUS-guided drainage are both better than ERP,and they are effective and safe methods especially for the patients with complication of pseudocysts and necrosis debris in pseudocysts.However,the hospitalization time of percutaneous drainage is longer. In addition,percutaneous drainage can be an alternative method after failed endoscopic drainage.