To report a case of an immunocompetent young adult male patient diagnosed with intracranial Aspergillus flavus infection， and to investigate the clinical features of this disease and related experience in diagnosis and treatment.A retrospective analysis was performed for the clinical data of a patient who had the initial presentation of high fever and headache and then progressed to meningoencephalitis， and the results of cerebrospinal fluid （CSF） metagenomic next-generation sequencing （mNGS） and treatment outcomes were summarized.The patient had an acute onset， with no response to empirical anti-infective therapy in the incipient stage， and then he gradually developed disturbance of consciousness and meningeal irritation sign. CSF analysis showed inflammatory changes， while conventional pathogen tests yielded negative results， and mNGS detected 27 specific sequences of Aspergillus flavus. The symptoms of the patient was significantly improved after antifungal therapy with voriconazole， with no recurrence after follow-up for 3 months.For unexplained central nervous system infections， especially those with negative results from conventional tests， mNGS can improve the detection rate of rare pathogens（e.g.，Aspergillus flavus）. Early diagnosis and targeted antifungal therapy are crucial for improving prognosis. This case highlights that invasive fungal infections should be considered even in immunocompetent individuals.
Aspergillus flavus

Folic acid is a fully oxidized synthetic folate with high bioavailability and stability which has been extensively prescribed to prevent congenital disabilities. Here we revealed the immunosuppressive effect of folic acid by targeting splenic marginal zone B (MZB) cells. Folic acid demonstrates avid binding with the Fc domain of immunoglobulin M (IgM), targeting IgM positive MZB cells in vivo to destabilize IgM-B cell receptor (BCR) complex and block immune responses. The induced anergy of MZB cells by folic acid provides an immunological escaping window for antigens. Covalent conjugation of folic acid with therapeutic proteins and antibodies induces immunological evasion to mitigate the production of anti-drug antibodies, which is a major obstacle to the long-term treatment of biologics by reducing curative effects and/or causing adverse reactions. Folic acid acts as a safe and effective immunosuppressant via IgM-mediated MZB cells targeting to boost the clinical outcomes of biologics by inhibiting the production of anti-drug antibodies, and also holds the potential to treat other indications that adverse immune responses need to be transiently shut off.

G protein-coupled receptor (GPR) 40, as one of GPRs family, plays a potential role in regulating glucose and lipid metabolism. To study the effect of GPR40 novel agonist SZZ15-11 on hyperglycemia and hyperlipidemia and its potential mechanism, spontaneous type 2 diabetic KKA^y mice, human hepatocellular carcinoma HepG2 cells and murine mature adipocyte 3T3-L1 cells were used. KKA^y mice were divided into four groups, vehicle group, TAK group, SZZ (50 mg·kg^-1) group and SZZ (100 mg·kg^-1) group, with oral gavage of 0.5% sodium carboxymethylcellulose (CMC), 50 mg·kg^-1 TAK875, 50 and 100 mg·kg^-1 SZZ15-11 respectively for 45 days. Fasting blood glucose, blood triglyceride (TG) and total cholesterol (TC), non-fasting blood glucose were tested. Oral glucose tolerance test and insulin tolerance test were executed. Blood insulin and glucagon were measured via enzyme-linked immunosorbent assay (ELISA). After mice′s execution, liver tissue was harvested to test TG and TC content. Then pathological morphology of liver was observed through hematoxylin-eosin (HE) staining, and the lipid metabolism relative signal pathway was analyzed by Western blot and RT-PCR. The experiments were approved by the Institutional Animal Care and Use Committee of the Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College. At the same time, Akt phosphorylation level in HepG2 cells and adiponectin in 3T3-L1 cells treated with TNFα were measured with Western blot. The results show that SZZ15-11 not only decreased blood glucose and lipid, improved insulin sensitivity, but also increased fasting blood glucagon and promoted insulin secretion after glucose loading in KKA^y mice. Additionally, SZZ15-11 alleviated hepatic steatosis and liver dysfunction in KKA^y mice. In liver tissue, SZZ15-11 increased AMPKα phosphorylation level and cholesterol metabolism relative gene Abcg8 transcription. In HepG2 cells, SZZ15-11 increased Akt phosphorylation level. In adipocyte 3T3-L1, SZZ15-11 recovered the decreased adiponectin expression by TNFα. This study proved that GPR40 agonist SZZ15-11 could be a candidate compound for regulating glucolipid metabolic disorder.

AIM:To establish and evaluate a colonoids model of intestinal barrier dysfunction with irritable bowel syndrome(IBS).METHODS:The colonic recess of 20～22 g male C57BL/6 mice were isolated and cultured in ma-trix glue to proliferate and differentiate into 3D hollow spheres with colonic epithelioid structure.The following experi-ments were carried out:(1)Colonoids and colonic tissues of mice were detected by immunofluorescence to identify colo-noids.(2)Fluorescein isothiocyanate dextran 4(FD4)evaluated the epithelial barrier function of colonoids.(3)To ex-plore the changes in the epithelial barrier of colonoids induced by interferon-γ(IFN-γ)at different concentrations and time points.FD4 and HE staining were used to evaluate the barrier function.RT-qPCR was used to detect the mRNA expres-sion of occludin and zonula occludens-1(ZO-1)in tight junctions of colonoids.Immunofluorescence was used to detect the distribution and localization of occludin and ZO-1 proteins.RESULTS:(1)The expression of EdU proliferation and in-testinal epithelial cell lineage markers in colonoids was consistent with that in mouse colonic tissues.(2)In the control group,FD4 did not infiltrate the colonoids lumen,but FD4 significantly infiltrated the colonoids lumen induced by ethyl-ene glycol-bis(β-aminoethyl ether)-N,N,N',N'-tetraacetic acid(EGTA).(3)From 18 h,the IFN-γ at 60,100,200 and 240 ng/mL could significantly infiltrate into the cavity of colonoids(0.033,0.032,0.042 and 0.001),and the barri-er injury of colonoids could be seen by HE staining.After 18 h,all concentrations of IFN-γ could significantly decrease the mRNA expression of occludin and ZO-1,and the fluorescence of occludin and ZO-1 decreased significantly(P<0.05).CONCLUSION:(1)The cultured organoids are colonoids with complete epithelial barrier.(2)IFN-γ could in-duce the decrease of the transcriptional levels of occludin and ZO-1 in the tight junction of colonoids,the decrease of the expression of corresponding proteins,and the change of localization and distribution,thus increasing the epithelial perme-ability of colonoids.This model is highly consistent with the pathophysiological state of IBS colonic mucosal barrier dys-function,which provides a new tool and method for studying the direction of colonic mucosal barrier dysfunction in IBS.

Clinicians need to focus on various points in the diagnosis and treatment of insomnia.This article prescribed the treatment protocol based on the unique features,such as insomnia in the elderly,women experiencing specific physiologi-cal periods,children insomnia,insomnia in sleep-breathing disorder patients,insomnia in patients with chronic liver and kidney dysfunction.It pro-vides some reference for clinicians while they make decision on diagnosis,differentiation and treat-ment methods.

Objective:To develop the Psychological Monitors'Interpersonal Trust Questionnaire in Colleges(PMITQC)and test its validity and reliability.Methods:A preliminary questionnaire was formulated by construc-ting a model of the psychological monitors'interpersonal trust.Totally 515 psychological monitors were selected for item analysis and exploratory factor analysis.In addition,556 psychological monitors were selected for confirmatory factor analysis and internal consistency reliability tests,of which 114 were retested after 4 weeks.The Trust Scale(TS)and Interpersonal Trust Scale(ITS)were used to test the criterion validity.Results:The PMITQC contained 22 items and was composed of four factors that accounted for 68.634％of the variance.The confirmatory factor a-nalysis showed that the four-factor structure model fitted nicely(x2/df=4.22,NFI=0.92,RFI=0.91,IFI=0.94,TLI=0.93,CFI=0.94,RMSEA=0.076).The criterion validity test showed that the total scores and scores of 4 factor of PMITQC were positively correlated with the total scores of TS and ITS(r=0.28-0.48,Ps＜0.01).The Cronbach's coefficients of the total questionnaire and the 4 factors ranged from 0.87 to 0.97 and the test-retest reli-abilities ranged from 0.73 to 0.89.Conclusion:The Psychological Monitors'Interpersonal Trust Questionnaire in Colleges has good validity and reliability.

To retrieve, evaluate, and integrate evidence related to the operational procedures of ambulatory blood pressure monitoring (ABPM) in adults, aiming to enhance the accuracy and effectiveness of ambulatory blood pressure monitoring.

By consulting ancient herbal medicines and medical books， combined with modern documents and field investigations， the textual research of Pheretima has been conducted to verify the name， origin， producing area， quality， harvesting and processing changes， and sort out the relationship of origin between ancient and modern times， so as to provide reference and basis for the development and utilization of the related famous classical formulas. Through textual research， it is known that there are many aliases for Pheretima， the rectification of name was "Qiuyin" or "Baijing Qiuyin" in materia medica books. In the Song dynasty and later prescription books， the prescription name is mostly Dilong. From the beginning of Yaowu Chuchanbian （《药物出产辨》）， Dilong was used as the rectification of name. It is widely distributed in our country， which is produced all over the country and mostly wild. According to ancient Pheretima with "Baijing Dilong"， "Jingbai Shenzi" and "Datiao" as the principles of medicine， combined with historical origin， producing area and easy access， it is confirmed that Pheretima used in ancient times to the present is mainly Pheretima aspergillum， and it also has many other Qiuyin as Pheretima for medicinal purposes. Chinese Pharmacopoeia has unified the origin of the Pheretima since the 1995 edition based on historical origins and actual harvesting conditions. The medicinal material processed by P. aspergillum was called Guangdilong， and the medicinal materials processed by P. vulgaris， P. guillelmi and P. pectinifera were called Hudilong. Since then， all the herbal books published in the future are in line with Chinese Pharmacopoeia that was implemented at that time. The authentic production areas of Guangdilong are Guangdong and Guangxi， and the authentic production areas of Hudilong is Jiangsu， Shanghai， Zhejiang and Anhui. The Guangdilong produced in Guangdong and Guangxi has the best quality. After harvesting， remove the soil and offal， wash and dry. Clinically cut into sections for medicine， or prepare medicine according to prescription. The Pheretima in ancient used "Baijing Dilong"， "Jingbai Shenzi" and "Datiao" as the mainstream quality evaluation standards. According to historical origins， P. aspergillum should be the main source of Pheretima， and its quality is better than other species. Therefore， it is recommended that Pheretima in Shentong Zhuyutang use P. aspergillum， which is produced in Guangdong， Guangxi and other places. After harvest， the abdomen was opened in time to remove the viscera and sediment， washed and dried.

By consulting ancient Chinese herbal medicines and medical books， combined with modern documents， the textual research of Polygonati Rhizoma has been conducted to verify the name， origin， bitter-flavored Polygonatum species， Latin name evolution， origin， quality evaluation， harvesting and processing changes， so as to provide reference and basis for the development and utilization of the famous classical formulas. Through textual research， it can be seen that there are many other names for Polygonati Rhizoma， and Huangjing is the correct name since Mingyi Bielu. Based on the original research， it is concluded that P. sibiricum and P. cyrtonema were the mainstream of Polygonati Rhizoma before the Tang dynasty， and P. kingianum was added in the Qing dynasty. According to the shape of medicinal materials， these Polygonatum species were called Jitou Huangjing， Jiangxing Huangjing and Dahuangjing. The harvest time of Polygonati Rhizoma is spring and autumn. After harvest， it is steamed and dried in the sun， and its processing method is mainly "nine steaming and nine storms". Bitter-flavored Polygonatum is mainly P. cirrhifolium， P. zanlanscianense， P. curvistylum and P. verticillatum， which are not suitable for medicine. Based on textual research， it is recommended that when developing famous classical formulas and health products with Polygonati Rhizoma as the main raw material， the origin and producing area should be clear and fixed， and P. sibiricum or P. cyrtonema with clear origin should be used. It is necessary to conduct germplasm survey and sampling in the producing area， establish a planting base and a traceability system for Polygonati Rhizoma， in order to control the quality and stabilize the efficacy of the products. The processing method of Polygonati Rhizoma can be determined according to the product function positioning.

OBJECTIVE: To evaluate the efficacy and safety of Tibetan medicine Ruyi Zhenbao Pills (RZPs) in the treatment of patients with motor and sensory dysfunction after stroke. METHODS: A total of 120 convalescent stroke patients hospitalized in the Rehabilitation Department of Guangdong Provincial Hospital of Chinese Medicine from June 2017 to December 2019 were enrolled in this trial. Patients were assigned to control (60 cases) and research (60 cases) groups by computer random assignment. All patients received internal treatment and modern rehabilitation training. On this basis, the research group was given oral RZPs for 4 weeks, while the control group was given oral placebo. The primary outcome was motor function of the affected side evaluated by simplified Fugl-Meyer Motion Assessment Scale (FMA-M). The secondary outcomes included sensory function, activity of daily living (ADL), quality of life, balance function, and pain, which were assessed by Fugl-Meyer Sensory Assessment Scale (FMA-S), Modified Barthel Index (MBI), Special Scale of the Quality of Life (SS-QOL), Berg Balance Scale (BBS), and Visual Analogue Scale (VAS), respectively. All of the assessments were performed before treatment, and 4 and 8 weeks after treatment. Vital signs, liver and kidney functions, routine blood test, blood coagulation profile, and routine urinalysis of patients were monitored. RESULTS: After 4-week treatment, the FMA-M, BBS and FMA-S scores in the research group significantly increased compared with the control group (P<0.05). At 8-week follow-up, the BBS and MBI scores in the research group were higher than the control group (P<0.05). There was no statistical difference between the 2 groups in the SS-QOL and VAS scores at 4 and 8 weeks (P>0.05). Moreover, after treatment, there was no significant difference in vital signs, liver and kidney functions, blood coagulation function, blood routine and urinalysis between the 2 groups (P>0.05). CONCLUSION RZPs improved limb motor, balance, and sensory functions of stroke patients during recovery period with good safety. (Trial registration No. NCT04029701).
Activities of Daily Living ; Humans ; Quality of Life ; Stroke/drug therapy* ; Stroke Rehabilitation ; Treatment Outcome