Objective To explore the molecular mechanism for the self-limitation of adenoviral infections in human airway,the different impacts of adenovirus serotype 5 ( Ad5 ) and serotype 7 ( Ad7 ) infections on mucin 1 ( MUC1 ) expression in airway epithelial cells were preliminarily investigated.Methods The Ad5 and the Ad7 infection models were established in A549 cell line.qRT-PCR was performed to determine the transcription of MUC1 mRNA,and the expression of MUC1 in A549 cells infected by Ad5 or Ad7 was by detected Western blot.Results An up-regulation of the MUC1 mRNA level were observed after Ad5 infection for 6 h(P＜0.05 ),and the protein expression level of MUC1 increased in a time-dependent manner in 48 hours of Ad5 infection,while similar response of MUC1 mRNA was absent in Ad7 infection (6 h),even after prolonged (20 h) treatment ( P ＞ 0.05 ).Conclusion This study reveals an up-regulation of MUC1 expression as one of the early immune response to Ad5 infection,which implies that MUC1 may function fully or partially as an anti-inflammatory factor in the self-limitation effect of Ad5 infection.However,type7 adenoviral infection,may introduce a mechanism otherwise,but through MUC1.

Objective To assess the role of pelvic ultrasound examination in discriminating between normal girls,isolated premature thelarche/pubarche /menarche and central precocious puberty (CPP).Methods Eighty-four isolated premature thelarche/pubarche /menarche cases,47 CPP cases,and 177 normal girls aged 0-10 years were recruited.All diagnoses were confirmed by the gonadotropin-releasing hormone-stimulation test.All subjects underwent pelvic ultrasound examination for the measurement of length,width,thickness,and volume of the uterine body,uterine cervix,and ovary,and the number of follicles with diameter≥ 4 mm.The groups were subdivided by age intervals when the difference in ultrasound measurements between CPP,isolated premature thelarche/pubarche/menarche,and normal girls were analyzed.Results 1) Differentiation between CPP and normal girls:for the 6-8 years,there were 11 variables elevated in CPP as compared to the normal girls.Uterine cervix thickness was the most efficient parameter as judged by the largest value of area under the ROC curve (0.958).The best cut-off,sensitivity,and specificity was 0.73 cm,93.30％,and 85.70％ respectively;for the 8-10 years,uterine body volume was the best parameter among the 10 elevated variables as judged by the largest area under the ROC curve (0.869),3.23 cm3 was the best cut-off limit with a sensitivity of 84.21％ and a specificity of 52.11％.2) Differentiation between isolated premature thelarche/pubarche/menarche and normal girls:for the 0-6 years,ovary thickness was the best variable as judged by the largest area under the ROC curve (0.806),0.98cm was the best cut-off limit with a sensitivity of 76.46％ and a specificity of 84.85 ％ ;for the 6-8 years,ovary width was the best variable among the 8 valuable variables for its largest area under the ROC curve (0.843),1.39 cm was the best cut-off limit with a sensitivity of 85.71％ and a specificity of 73.81％ respectively;for the 8-10 years,uterine cervix thickness was the best variable among the 5 valuable variables for its largest area under ROC curve (0.841),0.75 cm was the best cut-off limit with a sensitivity of 90.48％ and a specificity of 64.21％.3) Differentiation between CPP and isolated premature thelarche/ pubarche/menarche cases:for the 6-8 years,uterine cervix length and width were potential parameters.Uterine cervix length was the best variable for its largest area under the ROC curve(0.764),and 1.49 cm was the best cut-off limit,the corresponding sensitivity and specificity was 93.33％ and 55.17％ respectively;for the 8-10 years,3 variables could be used,among which uterine cervix length was the best variable for its largest area under the ROC curve (0.893),1.88 cm was the best cut-off limit with a sensitivity of 100％ and a specificity of 71.43％.Condusions Pelvic ultrasound examination is a valuable tool for the diagnosis and differentiation between CPP,isolated premature thelarche/pubarche /menarche and normal girls.

Objective:To investigate the potential drug interactions of outpatient prescriptions containing metformin combined with other drugs from the perspective of drug transporters.Methods:The prescriptions containing metformin that were used in the Outpatient Department of Hainan General Hospital, China between July and December 2019 were collected. The potential interaction between drugs and metformin used in the prescriptions was analyzed according to drug instructions, Drugbank, PubMed databases.Results:A total of 15 568 outpatient prescriptions containing metformin were collected, including 9 146 prescriptions for male patients and 6 422 prescriptions for female patients. A total of 14 902 prescriptions contained combined medication. The drugs used in combination included other hypoglycemic drugs, antiplatelet drugs, antihypertensive drugs, lipid-lowering drugs, and neuroprotective drugs. The drug transporters including aspirin, atorvastatin calcium, repaglinide, bisoprolol, metoprolol and clopidogrel had a potential interaction with metformin. There were 11 614 prescriptions containing drug transporters and metformin, including 5 938 prescriptions inhibiting organic cation transporter 1 and 5676 prescriptions inhibiting organic cation transporter 2.Conclusion:There is no incompatibility between the outpatient prescriptions containing metformin and the commonly used drugs for chronic diseases, but the outpatient doctors do not have enough knowledge about dose adjustment caused by potential interaction.

In a previous study, we screened thousands of long non-coding RNAs (lncRNAs) to assess their potential relationship with congenital heart disease (CHD). In this study, uc.4 attracted our attention because of its high level of evolutionary conservation and its antisense orientation to the CASZ1 gene, which is vital for heart development. We explored the function of uc.4 in cells and in zebrafish, and describe a potential mechanism of action. P19 cells were used to investigate the function of uc.4. We studied the effect of uc.4 overexpression on heart development in zebrafish. The overexpression of uc.4 influenced cell differentiation by inhibiting the TGF-beta signaling pathway and suppressed heart development in zebrafish, resulting in cardiac malformation. Taken together, our findings show that uc.4 is involved in heart development, thus providing a potential therapeutic target for CHD.

The climate in the Lingnan area south China is characterized by high temperature and rainy days， and in terms of the eating habits， the local people are more addicted to raw， cold and savory food， all of which make Lingnan people prone to a constitution of upper heat and lower cold， and pathological manifestations of upper heat and lower cold. It is believed that the main pathogenesis of hyperthyroidism in Lingnan area is the upper heat and the lower cold， manifested as spleen yang deficiency and stomach fire excess， or kidney water depletion and heart fire hyperactivity， leading to upper heat and lower cold syndrome caused by disharmony of yin and yang and abnormal ascending and descending. Therefore， spleen cold and stomach heat and disharmony between the heart and the kidney are the main syndromes of hyperthyroidism in Lingnan area. Modified Huanglian Decoction （黄连汤） is commonly used. Additionally， for spleen cold and stomach heat syndrome， Fushen （Sclerotium Poriae Pararadicis） and Baizhu （Rhizoma Atractylodis Macrocephalae） can be added to supplement spleen and stomach， thereby treating both the root and the branch. In terms of the disharmony between the heart and the kidney syndrome， Muli （Concha Ostreae） is usually added to subdue yang and supplement yin， together with Wuweizi （Fructus Schisandrae Chinensis） to supplement kidney and calm heart and Shashen （Radix Adenophorae seu Glehniae） to nourish yin and engender liquid， thereby enriching kidney-water and moistening heart-yin. Modification of the formulas is suggested in accordance with the syndromes to achieve a better effect.

Objective:To evaluate the application effect of the "group-based" teaching assistant (TA) guidance model in homogenized clinical skill training.Methods:A pilot study was conducted on the cardiopulmonary resuscitation training course, and 32 students majoring in clinical integrative Chinese and Western medicine (five-year program) who were admitted to Shanghai University of Traditional Chinese Medicine in 2018 were randomly divided into control group ( n = 16) and TA group ( n = 16). The control group received traditional teaching methods, and the TA group was further divided into subgroups A, B, C, and D, with four graduate TAs providing group-based teaching. The groups were compared in terms of their satisfaction and test scores. SPSS 25.0 was used for t-test and analysis of variance. Results:The satisfaction survey showed that compared with the control group, the TA group had significantly higher degree of satisfaction with the increased practical opportunities, clinical skill practical ability, learning effect, and overall satisfaction. The immediate test showed that there was no significant difference in test score between the TA group (85.19±2.93) points and the control group (82.75±4.52) points. The test 30 days later showed that the TA group (83.50±5.13) points had a significantly higher test score than the control group (74.68±3.87) points, and the control group had a significantly lower test score than that in the immediate test ( P <0.001); however, there was no significant difference in the TA group's score between the immediate test and the test 30 days later. Conclusion:The "group-based" TA guidance model has a good effect in homogenized clinical skill training, and has a stable long-term effect, with high student satisfaction.

  Objective  Adrenoleukodystrophy (ALD) is the most common peroxisomal diseases with high clinical and genetic heterogeneity. Our study is to analyze the phenotype and genotype characteristics of adult patients with ALD.  Methods  A total of 18 adult patients with ALD admitted to Beijing Tiantan Hospital from May 2016 to April 2021 were recruited, and their clinical manifestations, imaging features, and genetic results were comprehensively analyzed.  Results  Among 18 patients, 6(33%) patients were diagnosed as adrenomyeloneuropathy (AMN), 2(11%) were cerebral AMN, 5(28%) were adult cerebral ALD (ACALD), 2(11%) were childhood cerebral ALD (CCALD), 1(6%) were adolescent cerebral ALD (AdolALD), and 2(11%) were cerebellar variant of ALD. AMN patients presented with adult-onset stiffness and weakness of lower limbs as the initial and main symptoms, and can developed additional cerebral demyelination; In the case of cerebral ALD, ACALD is more common than CCALD and AdolALD. The prominent manifestations were psychiatric disorders, cognitive, and motor impairment. The imaging features were predominantly occipitoparietal involvement or predominantly frontal involvement with or without contrast enhancement marginal to the demyelinated areas; cerebellar ataxia is the main manifestation in patients with cerebellar variant, and the imaging feature was symmetrical involvement of the cerebellar dentate nucleus. Genetically, the most common mutation type was missense mutation (10/18, 55.6%), followed by frameshift mutation (7/18, 38.9%), and splice site mutation (1/18, 5.6%). Moreover, we found five novo mutations, all of which were frameshift mutations.  Conclusions  AMN is the most common subtype of adult patients with ALD. ACALD is common among the cerebral ALD. The proportion of cerebellar variant might have been underestimated.

Objective:To investigate the predictive value of serum D-dimer combined with myocardial injury markers on admission for early identification of high-risk patients with acute myocarditis.Methods:Patients hospitalized for acute myocarditis in China-Japan Friendship Hospital were retrospectively enrolled from 2010 to 2021. Patients were divided into the high D-dimer level group and low D-dimer level group according to the median value of D-dimer measured by immunoturbidimetry within 24 h of admission. In-hospital adverse events were defined as death, cardiogenic shock, malignant ventricular arrhythmia and new-onset heart failure. Multivariate logistic analysis was used to explore the independent predictors of in-hospital adverse events, and receiver operating characteristic curve was used to evaluate the predictive value.Results:A total of 106 patients were analyzed, including 52 high level D-dimer patients and 54 low level D-dimer patients, with an average age of (36±16) years, and 62.3% were male. Compared with the low D-dimer level group, patients in the high D-dimer level group had lower mean systolic blood pressure [(114±21) mmHg vs. (121±14) mmHg] and diastolic blood pressure [(71±13) mmHg vs. (76±10) mmHg], higher heart rate [(97±26) beats/min vs. (79±15) beats/min], higher C-reactive protein levels [6.82 (1.61, 20.05) mg/dL vs. 1.30 (0.13, 8.93) mg/dL] and creatinine levels [86.95 (67.63, 117.83) μmol/L vs. 68.80 (60.18, 81.93) μmol/L] on admission. The proportion of patients having QRS interval >120 ms on electrocardiogram was higher in high D-dimer level group (25.0% vs. 7.4%). There was no significant difference in patients with positive myocardial injury biomarkers between the two groups. The incidence of in-hospital adverse events was higher in the high D-dimer level group (67.3% vs. 22.2%, P<0.001). Multivariate logistic analysis showed that serum D-dimer levels and elevated myocardial injury markers on admission were independently associated with in-hospital adverse events. The area under the curve (AUC) of elevated serum D-dimer level on admission for predicting in-hospital adverse events was 0.781 (95% CI: 0.690-0.873), the sensitivity was 74.5%, and the specificity was 71.2%. When combined with positive cardiac biomarkers, the AUC was 0.831 (95% CI: 0.752-0.910) with a sensitivity of 80.9% and a specificity of 78.0%. Conclusions:Elevated D-dimer level on admission can predict the risk of in-hospital adverse events in patients with acute myocarditis. The combination of cardiac injury biomarkers can improve the predictive value.

Mucosal vaccines can effectively induce an immune response at the mucosal site and form the first line of defense against microbial invasion. The induced mucosal immunity includes the proliferation of effector T cells and the production of IgG and IgA antibodies, thereby effectively blocking microbial infection and transmission. However, after a long period of development, the transformation of mucosal vaccines into clinical use is still relatively slow. To date, fewer than ten mucosal vaccines have been approved. Only seven mucosal vaccines against coronavirus disease 2019 (COVID-19) are under investigation in clinical trials. A representative vaccine is the adenovirus type-5 vectored COVID-19 vaccine (Ad5-nCoV) developed by Chen and coworkers, which is currently in phase III clinical trials. The reason for the limited progress of mucosal vaccines may be the complicated mucosal barriers. Therefore, this review summarizes the characteristics of mucosal barriers and highlights strategies to overcome these barriers for effective mucosal vaccine delivery.

Background Imidacloprid is a neonicotinoid insecticide that is widely used in agricultural production, with a high detection rate in human biological samples. Previous studies have shown a high correlation between imidacloprid exposure and liver injury, but the specific mechanism is still unknown. Objective To observe potential toxic effects of HepG2 cells and its perturbation of non-targeted metabolic profile after imidacloprid exposure, and to explore possible molecular mechanisms of hepatotoxicity of imidacloprid by analyzing invovlved biological processes and signaling pathways. Methods HepG2 cell suspension was prepared and seeded in a 96-well plate, which was divided into blank control group, dimethyl sulfoxide (DMSO) solvent control group and imidacloprid exposure groups with multiple concentrations. Each group was set with 5 parallel samples. The viability of HepG2 cells viability were determined after 8 h of exposure to different concentrationsof imidacloprid (1, 2.5, 5, 7.5, 10 mmol·L⁻¹), and the dose-effect relationship was analyzed. A proper concentration (3 mmol·L⁻¹ with 80% viability) was chosen for imidacloprid exposure, non-targeted metabolomic analysis was applied to the cultivated HepG2 cells using UHPLC-Q-TOF/MS technology, the differential metabolites between groups were screened, and the bioprocess and related signaling pathways of their enrichment were annotated using the Kyoto Encyclopedia of Genes and Genomes (KEGG) database. Results Compared to the other two groups, the survival rates of HepG2 cells in the imidacloprid exposure groups decreased. A survival rate of about 86% of HepG2 cells was found in HepG2 cells exposed to 2.5 mmol·L⁻¹ imidacloprid exposure. The non-targeted metabolomics studies showed that 61 metabolites were significantly affected in HepG2 cells after 3 mmol·L⁻¹ imidacloprid exposure, including creatine (variable importance in projection VIP=1.11, P<0.001), arginine (VIP=1.47, P=0.048), taurine (VIP=4.28, P=0.001), and α-D-glucose (VIP=1.90, P=0.006). The differential metabolites enriched in bioprocess and related signaling pathways were mainly directed to mTOR signaling pathways (P<0.001), arginine and proline metabolism (P=0.002), and galactose metabolism (P=0.015). Conclusion Imidacloprid exposure can significantly inhibit the survival rate of HepG2 cells, and interfere with the mTOR signaling pathway, arginine and proline metabolism, galactose metabolism, and so on.