Objective To observe the efficacy and safety of Morinda officinalis oligosaccharides in the continuation treatment of mild and moderate depression.Methods An open,single-arm,multi-center design was adopted in our study.Adult patients with mild and moderate depression who had received acute treatment of Morinda officinalis oligosaccharides were enrolled and continue to receive Morinda officinalis oligosaccharides capsules for 24 weeks,the dose remained unchanged during continuation treatment.The remission rate,recurrence rate,recurrence time,and the change from baseline to endpoint of Hamilton Depression Scale(HAMD),Hamilton Anxiety Scale(HAMA),Clinical Global Impression-Severity(CGI-S)and Arizona Sexual Experience Scale(ASEX)were evaluated.The incidence of treatment-related adverse events was reported.Results The scores of HAMD-17 at baseline and after treatment were 6.60±1.87 and 5.85±4.18,scores of HAMA were 6.36±3.02 and 4.93±3.09,scores of CGI-S were 1.49±0.56 and 1.29±0.81,scores of ASEX were 15.92±4.72 and 15.57±5.26,with significant difference(P＜0.05).After continuation treatment,the remission rate was 54.59％(202 cases/370 cases),and the recurrence rate was 6.49％(24 cases/370 cases),the recurrence time was(64.67±42.47)days.The incidence of treatment-related adverse events was 15.35％(64 cases/417 cases).Conclusion Morinda officinalis oligosaccharides capsules can be effectively used for the continuation treatment of mild and moderate depression,and are well tolerated and safe.

Objective:To study the effect and mechanism of Zuoguiwan on the autophagy of cells in the skin during the development of congenital kidney-deficient mice， and to explore the application value of kidney tonifying and essence filling method in abnormal growth and development. Method:36 rats with a 2∶1 ratio of male to female were paired， and the pregnant rats were stimulated by combined stress method to build a model of congenital kidney-deficient rats. According to different treatment methods， the pregnant rats were divided into the control group， the kidney-deficient group， and the Zuoguiwan low and high dose groups （2， 8 g·kg^-1）. The control group was given normal saline without modeling. Kidney deficiency group was modeled before intragastric administration of normal saline. Zuoguiwan small dose and high dose groups received intragastric administration of Zuoguiwan suspension. 21 days after the birth of mice， the back skin was taken to observe the skin microstructure and morphology of the mice by HE staining and detect the thickness of dermis and epidermis. The gene and protein expression levels of Wingless3a and β-catenin in the skin of neonatal rats were measured by Western blot and Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR）. Double immunofluorescence assay was used to detect the skin autophagy indicators Microtubule-associated protein light chain 3 （LC3）and Sequestosome 1 （SQSTM1-p62）. Result:In the control group， the skin layers were clear and the structure was normal， in the kidney deficiency group， the collagen arrangement in the dermis was loose， the skin composition in Zuoguiwan low and high dose groups was basically normal. Compared with the control group， the epidermal layer of the kidney deficiency group was thickened and the dermis was thinned （P<0.05）. Compared with the kidney deficiency group， the thickness changes of epidermal layer and dermis layer were significantly restored in Zuoguiwan low and high dose groups （P<0.05）. Compared with the control group， the expression of Wnt3a and β-catenin protein and gene in the kidney deficiency group significantly decreased （P<0.05）. Compared with the kidney deficiency group， Wnt3a and β-catenin protein and gene expression increased in Zuoguiwan low and high dose groups （P<0.05）. At the same time， immunofluorescence assay showed that compared with the control group， the expression of LC3 was up-regulated and the expression of SQSTM1-p62 was down-regulated in the kidney deficiency group， while Zuoguiwan could reverse such abnormal expression （P<0.05）. Conclusion:Zuoguiwan can down-regulate the autophagy level of skin cells and improve the abnormal skin development of congenital renal deficiency by increasing the expression of Wnt3a and β-catenin protein and gene in the skin of neonatal rats.

OBJECTIVE: To study the expression of multiple negative costimulatory molecules on peripheral blood T cells in patients with acute myeloid leukemia (AML) and its affection on prognosis. METHODS: The peripheral blood samples from patients with newly diagnosed AML, complete remission (CR), and no-remission (NR) were collected, the expression levels PD-1、VISTA and TIM-3 in CD4 and CD8 T cells were detected by flow cytometry , and the clinical data of patients were analyzed. RESULTS: The expression levels of PD-1、VISTA and TIM-3 of CD4 and CD8 T cells in the newly diagnosed AML patients were significantly higher than those in control group (P＜0.05). The expression levels of PD-1、TIM-3 and VISTA of CD4 and CD8 T cells in the CR group were significantly lower than those in newly diagnosed and the NR group (P＜0.05). The TIM-3 expression level positively correlated with VISTA expression level of CD4 and CD8 T cells in newly diagnosed AML patients (r=0.85 and 0.73). The VISTA and PD-1 expression level of CD4 T cells in newly diagnosed AML, NR after first induction chemotherapy and high risk patients significantly increased (P＜0.05), the TIM-3 expression level of CD8 T cells in high risk group significantly increased (P＜0.05), and the VISTA expression level of CD8 T cells in CBFβ-MYH11 mutation-positive group significantly decreased (P＜0.05). CONCLUSION The expression of PD-1、TIM-3 and VISTA in AML peripheral blood T cells may be involved in the immune escape of AML and can be the targets of treatment for acute myeloid leukemia patients.
B7 Antigens ; CD8-Positive T-Lymphocytes ; Flow Cytometry ; Hepatitis A Virus Cellular Receptor 2 ; Humans ; Leukemia, Myeloid, Acute ; Programmed Cell Death 1 Receptor

To scientifically evaluate the intervention effect of Chinese medicine preventive administration(combined use of Huo-xiang Zhengqi Oral Liquid and Jinhao Jiere Granules) on community population in the case of coronavirus disease 2019(COVID-19), a large cohort, prospective, randomized, and parallel-controlled clinical study was conducted. Total 22 065 subjects were included and randomly divided into 2 groups. The non-intervention group was given health guidance only, while the traditional Chinese medicine(TCM) intervention group was given two coordinated TCM in addition to health guidance. The medical instructions were as follows. Huoxiang Zhengqi Oral Liquid: oral before meals, 10 mL/time, 2 times/day, a course of 5 days. Jinhao Jiere Granules: dissolve in boiling water and take after meals, 8 g/time, 2 times/day, a course of 5 days, followed up for 14 days, respectively. The study found that with the intake of medication, the incidence rate of TCM intervention group was basically maintained at a low and continuous stable level(0.01%-0.02%), while the non-intervention group showed an overall trend of continuous growth(0.02%-0.18%) from 3 to 14 days. No suspected or confirmed COVID-19 case occurred in either group. There were 2 cases of colds in the TCM intervention group and 26 cases in the non-intervention group. The incidence of colds in the TCM intervention group was significantly lower(P<0.05) than that in the non-intervention group. In the population of 16-60 years old, the incidence rate of non-intervention and intervention groups were 0.01% and 0.25%, respectively. The difference of colds incidence between the two groups was statistically significant(P<0.05). In the population older than 60 years old, they were 0.04% and 0.21%, respectively. The incidence of colds in the non-intervention group was higher than that in the intervention group, but not reaching statistical difference. The protection rate of TCM for the whole population was 91.8%, especially for the population of age 16-60(95.0%). It was suggested that TCM intervention(combined use of Huoxiang Zhengqi Oral Liquid and Jinhao Jiere Granules) could effectively protect community residents against respiratory diseases, such as colds, which was worthy of promotion in the community. In addition, in terms of safety, the incidence of adverse events and adverse reactions in the TCM intervention group was relatively low, which was basically consistent with the drug instructions.
Adolescent ; Adult ; Betacoronavirus ; Coronavirus Infections ; drug therapy ; Drugs, Chinese Herbal ; Humans ; Medicine, Chinese Traditional ; Middle Aged ; Pandemics ; Pneumonia, Viral ; drug therapy ; Prospective Studies ; Young Adult

Objective　CARD9 can activate several pathways involved in immunity, such as NF-ΚB, MAPK, etc. However the mechanism of this process has not yet been elucidated. For conducting relevant experiments in vitro, a prokaryotic expression vector of CARD9-MBP fusion protein has to been construct, and the fusion protein need to be expressed and purified.　Methods　The coding sequence of CARD9 and MBP genes were amplified by PCR and the recombinant plasmid was correctly inserted into the pET-30a(+) vector. The recombinant plasmid was transformed into E.coli DH5α competent cells and proceeded PCR identification, restriction analysis and gene sequencing. The correct recombinant plasmid was transformed into E.coli BL21(DE3) competent cells. The target protein was induced to express by IPTG under different conditions. Relative molecular weight of the target protein was detected by SDS-PAGE electrophoresis. The CARD9-MBP fusion protein was purified by MBP maltose chromatography column and gel filtration chromatography column, and identificated by MALDI-TOF mass spectrometry after MBP-tag to be removed by HRV3C enzyme.　Results　The CARD9-MBP fusion protein was successfully constructed and confirmed by PCR and restriction analysis. The result of gene sequencing was consistent with the target sequence. The SDS-PAGE electrophoresis showed that the target protein with molecular mass (MR) about 105 000 was successfully induced to express in E.coli BL21 (DE3). A quite pure CARD9-MBP fusion protein was obtained by purification of MBP maltose chromatography column. Identification by MALDI-TOF mass spectrometry demonstrated that the target protein after MBP-tag to be removed by HRV3C enzyme is CARD9 protein. In the later stage, gel filtration chromatography column was used to obtain further pure CARD9-MBP fusion protein.　Conclusion　The prokaryotic expression vector of CARD9-MBP fusion protein was successfully constructed and a large number of soluble protein expressed. The purified target protein can be obtained by purification with MBP maltose chromatography column and gel filtration chromatography column.

Objective Erythroderma is a very serious disease that affects nearly the entire cutaneous surface and are highly subjected to secondary hypoalbuminemia, infection, cardiovascular diseases, complex causes and high death rates. The article aimed to explore the etiology, comorbidities and complicated infection of erythroderma.Methods Retrospective analysis was conducted on clinical data of 95 cases of erythroderma in our department from January 2009 to August 2016. Observations were made on the patients' clinical characteristics, etiology and inducement, lab examination, complications and complicated infection.Results There were 73 first-episode and 22 recurrent patients, among which 14 cases are psoriasis as the basic disease. As to etiological factors, there were 57 cases secondary to other skin diseases (60%) and 25 cases by drug reactions (26%). As to inducing factors, there were 6 cases by upper respiratory tract infection, 38 cases by irrational application of glucocorticoids, and 7 cases by external stimulants (traditional Chinese medicine scrubbing and external medicinal liquor). The main complications were 38 cases of cardiovascular diseases (40%). The complicated infection rates of plasma albumin in patients <35g/L and ≥35g/L were 65.78% and 12.28%(P<0.01). The complicated infection rates of the patients with hypoalbuminemia and electrolyte disturbance were 44.2% and 25% respectively (P<0.05).Conclusion The erythroderma is mainly secondary to previous skin diseases, mostly psoriasis, with cardiovascular diseases as the main comorbidities. In clinical practice, importance should be attached to monitoring decreased plasma albumin level and electrolyte disturbances in order to reduce the risk of infection.

Introduction: Human papillomavirus (HPV) testing is used as a means of triaging cervico-vaginalsmears with low grade squamous abnormalities or as part of co-testing with cytology. While HPVtesting has a high sensitivity, it has a low specificity in detecting cervical intraepithelial neoplasiagrade 2 and above (CIN 2+) leading to unnecessary colposcopy referrals. We investigate the accuracyof the p16/Ki-67 dual immunocytochemical stain in determining the presence of CIN 2+ lesions onhistology and its potential as a superior biomarker for triage. Methods: Liquid based cervico-vaginalcytology specimens with squamous abnormalities and corresponding histology from 97 women withsubsequent colposcopy and biopsy were included. The specimens were then subjected to the dual stainand Roche Cobas 4800 multiplex real time PCR HPV DNA testing. The sensitivity and specificity ofthe dual stain and HPV testing were calculated using CIN 2+ on histology as a reference standard.Results: The sensitivity and specificity of the dual stain in detecting histology proven CIN 2+ was93.7% and 76.5% while HPV testing was 85.7% and 14.7% respectively. Of the 44 women withASCUS or LSIL on cytology, the dual stain also reduced the number of unnecessary colposcopyreferrals from 27 to 7 when used as a triage marker compared to HPV testing. Conclusion: p16/Ki-67dual stain was more sensitive and specific than HPV testing in determining the presence of CIN 2+on histology. It could triage low grade cervico-vaginal specimens more effectively and potentiallyhelp women avoid unnecessary colposcopies. Future studies are needed to further evaluate its rolein cervical cancer screening programmes.

Objective:To investigate the recurrence factors of small intestine gastrointestinal stromal tumor (GIST ) after resection .Methods :The clinicopathological data of 67 patients with recurrent small intestine GIST admitted to Zhongshan Hospital affiliated to Fudan University from January 2004 to December 2013 were retrospectively analyzed .Kaplan‐Meier method was used to analyze the effects of different factors on the recurrence time of small intestine GIST .Cox multi‐factor regression analysis was used to analyze the independent factors of recurrence of small intestine GIST .Results :Univariate analysis revealed that the median recurrence time significantly shortened in patients with tumor diameter more than 10 cm , mitotic rate greater than or equal to 30/50 HPF ,tumor rupture ,and R0 resection ,and the difference was significant (P<0 .05) .Multivariate analysis demonstrated that tumor rupture and surgical methods were independent prognostic factors for the recurrence of small intestine GIST (P< 0 .05) .Conclusions :R0 resection and intraoperative tumor rupture avoidance can prolong the recurrence time of small intestine GIST .

Objective To adapt to the acute cerebral ischemia re-search , we modified the permanent bilateral common carotid artery occlu-sion (2VO) rat model.Methods Global ischemia models were estab-lished by permanent ligation of bilateral common, internal, external ca-rotid arteries (6VO) and the 2VO method respectively.The sham group were done simultaneously.Then the differences among three groups in mortality, behavioral score tests,pathological morphology, the expression of inflammatory factor by immunohistochemical method, and the percen-tage of cell apoptosis were compared.Results Twenty-four hours after operations, the mortality of 6VO group ( 40% ) was obviously higher than 2VO group ( 0 ) .The results of behavioral score, necrosis rate of neurons, the expression of inflammatory factors and cell apoptosis in hippocampus CA1 area in 6VO group were significantly higher than 2VO group and sham group ( P <0.05 ) .Conclusion The modified 6VO model is an ideal way to observe acute global ischemic injury in rats.

PURPOSE: The universal organic solvent dimethyl sulfoxide (DMSO) can be used as a differentiation inducer of many cancer cells and has been widely used as a solvent in laboratories. However, its effects on breast cancer cells are not well understood. The aim of this study is to investigate the effect and associated mechanisms of DMSO on mouse breast cancer. METHODS: We applied DMSO to observe the effect on tumors in a mouse breast cancer model. Tumor-associated macrophages (TAMs) were tested by flow cytometry. Ex vivo tumor microenvironment was imitated by 4T1 cultured cell conditioned medium. Enzyme-linked immunosorbent assays were performed to detect interleukin (IL)-10 and IL-12 expression in medium. To investigate the cytotoxicity of DMSO on TAMs, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays were performed. RESULTS: We found that DMSO produced tumor retardation when injected into mouse peritoneal cavities in a certain concentration range (0.5-1.0 mg/g). Furthermore, as detected by flow cytometry, TAM subtypes were found to be transformed. We further imitated a tumor microenvironment in vitro by using 4T1 cultured cell conditioned medium. Similarly, by using low concentration DMSO (1.0%-2.0% v/v), TAMs were induced to polarize to the classically activated macrophage (M1-type) and inhibited from polarizing into the alternatively activated macrophage (M2-type) in the conditioned medium. IL-10 expression in tumors was reduced, while IL-12 was increased compared with the control. Furthermore, we reported that 2.0% (v/v) DMSO could lead to cytotoxicity in peritoneal macrophages after 48 hours in MTT assays. CONCLUSION: Our findings suggest that DMSO could exert antitumor effects in 4T1 cancer-bearing mice by reversing TAM orientation and polarization from M2- to M1-type TAMs. These data may provide novel insight into studying breast cancer immunotherapy.
Animals ; Breast Neoplasms* ; Breast* ; Cells, Cultured ; Culture Media, Conditioned ; Dimethyl Sulfoxide* ; Enzyme-Linked Immunosorbent Assay ; Flow Cytometry ; Immunotherapy ; Interleukin-10 ; Interleukin-12 ; Interleukins ; Macrophages* ; Macrophages, Peritoneal ; Mice* ; Tumor Microenvironment