OBJECTIVE: Preliminary assessment of rabies virus neutralizing activity, safety and immunogenicity of a recombinant human rabies antibody (NM57) compared with human rabies immunoglobulin (HRIG) in Chinese healthy adults. METHODS: Subjects were randomly (1:1:1) allocated to Groups A (20 IU/kg NM57), B (40 IU/kg NM57), or C (20 IU/kg HRIG). One injection was given on the day of enrollment. Blood samples were collected on days -7 to 0 (pre-injection), 3, 7, 14, 28, and 42. Adverse events (AEs) and serious AEs (SAEs) were recorded over a period of 42 days after injection. RESULTS: All 60 subjects developed detectable rabies virus neutralizing antibodies (RVNAs) (> 0.05 IU/mL) on days 3, 7, 14, 28, and 42. The RVNA levels peaked on day 3 in all three groups, with a geometric mean concentration (GMC) of 0.2139 IU/mL in Group A, 0.3660 IU/mL in Group B, and 0.1994 IU/mL in Group C. At each follow-up point, the GMC in Group B was significantly higher than that in Groups A and C. The areas under the antibody concentration curve over 0-14 days and 0-42 days in Group B were significantly larger than those in Groups A and C. Fifteen AEs were reported. Except for one grade 2 myalgia in Group C, the other 14 were all grade 1. No SAEs were observed. CONCLUSION The rabies virus neutralizing activity of 40 IU/kg NM57 was superior to that of 20 IU/kg NM57 and 20 IU/kg HRIG, and the rabies virus neutralizing activity of 20 IU/kg NM57 and 20 IU/kg HRIG were similar. Safety was comparable between NM57 and HRIG.
Adult ; Antibodies, Neutralizing ; Antibodies, Viral ; Data Collection ; Humans ; Rabies/prevention & control* ; Rabies Vaccines/adverse effects* ; Rabies virus/genetics*

Objective: To observe the clinical effect and safety of Shanhaidan Granules (SHDG) combined with tadalafil tablets (TT) in the treatment of ED. METHODS: In this open multi-center case-control clinical trial, we enrolled 247 ED patients according to the designed criteria, and treated them orally with SHDG at 10 g per time tid (n = 74), TT at 5 mg per time bid (n = 52), or SHDG + TT at the above doses (n = 121), all for 8 weeks. Before and after medication, we recorded the IIEF-6, erection hardness scores (EHS), traditional Chinese medicine syndromes (TCMS) scores, penile cavernous blood flow parameters and adverse reactions, and compared them between the 3 groups of patients. RESULTS: After 8 weeks of treatment, all the patients showed significantly increased IIEF-6, EHS and TCMS scores in comparison with the baseline (P < 0.05). The total effectiveness rates in the SHDG, TT and SHDG + TT groups were 60.8%, 67.3% and 69.4% respectively based on the IIEF-6 scores, remarkably higher in the TT and SHDG + TT groups than in the SHDG group (P < 0.05), and 40.5%, 32.7% and 63.6% respectively according to the TCMS scores, markedly higher in the SHDG and SHDG + TT groups than in the TT group (P < 0.05). Single-center data manifested significantly increased peak systolic velocity (PSV) of the penile artery in the SHDG + TT and TT groups (P < 0.05). The improvement values of relevant parameters were remarkably higher in the SHDG + TT group than in the TT and SHDG groups, so were IIEF-6 scores in the TT than in the SHDG group, and TCM syndromes in the SHDG than in the TT group. No medication-related adverse events were found in any of patients after treatment, except for some mild side effects including muscle soreness and gastrointestinal reactions in a few cases, all soon relieved, none with abnormalities in blood and urine routine tests or hepatic and renal function indicators. CONCLUSIONS Shanhaidan Granules combined with tadalafil can significantly improve the erectile function and reduce TCM syndromes in ED patients, and therefore can be applied effectively and safely in clinical practice./.
Erectile Dysfunction/drug therapy* ; Humans ; Male ; Medicine, Chinese Traditional ; Penile Erection ; Syndrome ; Tadalafil/therapeutic use*

ObjectiveThe aim of this study is to investigate the proportion of DN2 cell and the correlation between the expression of calcium ion release activated calcium ion channel（ Ca²⁺ release-activated Ca²⁺， CRAC） protein in DN2 cells and the clinical activity of lupus nephritis （LN）. MethodsFlow cytometry was used to detect the proportion of DN2 cells in healthy controls （HC， n=15）， LN （HC， n=30）， rheumatoid arthritis （RA， n=15） and primary Sjogren syndrome （pSS， n=15） patients and the expression of SOCE protein Orai1 in DN2 cells. One-way ANOVA was used to analyze the differences among the four groups. The correlation between Orai1 expression and LN disease activity was analyzed by Pearson correlation analysis. ResultsThere was a statistically significant difference in the proportion of DN2 cells in peripheral blood among the four groups （F= 9.315， P＜0.000 1）. The proportion of DN2 cells in the peripheral blood of patients with LN was significantly higher than that of HC， RA and pSS ［（2.60±2.20）% vs.（0.68±0.56）% vs.（0.69±0.45）% vs.（1.04±0.72）%］ and was correlated with 24-hour urinary protein excretion （r=0.599 9， P=0.000 5）. There was a statistically significant difference in the Orai1 expression in DN2 cells among the four groups （F= 7.935， P＜0.000 1）. The Orai1 expression in DN2 cells of LN was significantly higher than that of HC， RA and pSS （2.30±1.50 vs. 0.86±0.39 vs. 1.34±0.57 vs. 1.13±0.64）. Orai1 expression in DN2 cells was positively correlated with SLEDAI （r=0.56， P＜0.005）， blood anti-dsDNA antibody level （r=0.43， P＜0.05） and 24-hour urinary protein excretion （r=0.44， P＜0.05）， and negatively correlated with complement C3 （r=-0.39， P＜0.05）. ConclusionsThe proportion of DN2 cells and the expression of Orai1 increases in patients with LN and is correlated with disease activity. SOCE of DN2 cells may be a potential therapeutic target for LN.

BACKGROUND: Zinc finger and BTB domain-containing protein 46 (Zbtb46) is a transcription factor identified in classical dendritic cells, and maintains dendritic cell quiescence in a steady state. Zbtb46 has been reported to be a negative indicator of acute myeloid leukemia (AML). We found that Zbtb46 was expressed at a relatively higher level in hematopoietic stem and progenitor cells (HSPCs) compared to mature cells, and higher in AML cells compared to normal bone marrow (BM) cells. However, the role of Zbtb46 in HSPCs and AML cells remains unclear. Therefore, we sought to elucidate the effect of Zbtb46 in normal hematopoiesis and AML cells. METHODS: We generated Zbtb46 and Zbtb46Mx1-Cre mice. The deletion of Zbtb46 in Zbtb46Mx1-Cre mice was induced by intraperitoneal injection of double-stranded poly (I). poly (C) (poly(I:C)), and referred as Zbtb46 cKO. After confirming the deletion of Zbtb46, the frequency and numbers of HSPCs and mature blood cells were analyzed by flow cytometry. Serial intraperitoneal injection of 5-fluorouracil was administrated to determine the repopulation ability of HSCs from Zbtb46 and Zbtb46 cKO mice. The correlation between Zbtb46 expression and prognosis was analyzed using the data from the Cancer Genome Atlas. To investigate the role of Zbtb46 in AML cells, we knocked down the expression of Zbtb46 in THP-1 cells using lentiviral vectors expressing small hairpin RNAs targeting Zbtb46. Cell proliferation rate was determined by cell count assay. Cell apoptosis and bromodeoxyuridine incorporation were determined by flow cytometry. RESULTS: The percentages and absolute numbers of HSPCs and mature blood cells were comparable in Zbtb46 cKO mice and its Zbtb46 littermates (Zbtb46vs. Zbtb46 cKO, HPC: 801,310 ± 84,282 vs. 907,202 ± 97,403, t = 0.82, P = 0.46; LSK: 86,895 ± 7802 vs. 102,210 ± 5025, t = 1.65, P = 0.17; HSC: 19,753 ± 3116 vs. 17,608 ± 3508, t = 0.46, P = 0.67). The repopulation ability of HSCs from Zbtb46Mx1-Cre mice was similar to those from Zbtb46 control (P = 0.26). Zbtb46 had elevated expression in AML cells compared to total BM cells from normal control. Knockdown of Zbtb46 in THP-1 cells led to a significant increase in cell apoptosis and reduced cell growth and proliferation. CONCLUSION Collectively, our data indicate that Zbtb46 is essential for survival and proliferation of AML cells, but dispensable for normal hematopoiesis.

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 To identify the disease-causing gene in a Chinese pedigree with familial dilated cardiomyopathy (DCM) by whole-exome sequencing.Methods After collecting the clinical data and extracting the whole blood genomic DNA of the 5 family members form a Chinese DCM pedigree,whole-exome sequencing was performed to search the causative genes.Familial co-segregation analysis among the pedigree was subsequently confirmed by traditional Sanger sequencing.Results We performed whole exome sequencing (WES) on representative affected individuals and unaffected familial members from this pedigree.After comparison with variants identified in affected individuals and unaffected individuals,along with previously reported genetic mutations associated with DCM,we found that a heterozygous variant c.961 C＞T (p.Arg321Ter) in exon 6 of the LMNA gene in affected individuals matched the criteria to be the potential disease-causing gene,which was confirmed by Sanger sequencing.This stop-gain mutation leads to only a small part of LMNA-coding protein expressed,therefore we concluded that LMNA c.961 C＞T should be the causative mutation for this familial DCM case.Conclusions The nonsense mutation c.961 C＞ T in gene LMNA identified by whole-exome sequencing might be the pathogenic mutation in this DCM pedigree.

Penile hypersensitivity plays an important role in premature ejaculation (PE), but differences in penile sensitivity among subtypes of PE are unknown. Therefore, we compared penile sensory thresholds in PE subtypes of lifelong and acquired PE, PE with and without erectile dysfunction (ED), PE with an intravaginal ejaculation latency time ≤1 min and >1 min, and PE with and without orgasmic pleasure perceptual dysfunction. During August 2014 to January 2016, 136 patients with PE were included. Penile warm, cold, and vibratory thresholds were measured. Data of clinical characteristics, sexual life, Premature Ejaculation Diagnostic Tool (PEDT) score, and the 5-item version of the International Index of Erectile Function (IIEF-5) score were collected. Vibratory thresholds of the PE with ED group were higher in the right coronal sulcus (median amplitude: 4.92 vs 3.65 μ m, P = 0.02) and the right penile shaft (median amplitude: 3.87 vs 3.30 μ m, P = 0.03), while differences in penile sensory thresholds between other subtypes were not significant. The median PEDT score was lower in the PE without ED group (12 vs 14, P < 0.001). The IIEF-5 and PEDT scores were negatively correlated (r = -0.29, P < 0.001). Patients with orgasmic pleasure perceptual dysfunction had a lower median IIEF-5 score (20 vs 21, P = 0.02). Patients with PE and ED had lower penile sensitivity, and ED was associated with more severe symptoms and weaker orgasmic pleasure perception. In men with PE, management of comorbid ED is necessary. In case of side effects in erectile function, topical anesthetics should be cautiously used in men with PE and ED.
Adolescent ; Adult ; Ejaculation ; Erectile Dysfunction/physiopathology* ; Humans ; Male ; Middle Aged ; Orgasm ; Penis/physiology* ; Physical Stimulation ; Pleasure ; Premature Ejaculation/physiopathology* ; Prospective Studies ; Sensory Thresholds ; Sexual Dysfunctions, Psychological ; Sexuality ; Surveys and Questionnaires ; Temperature ; Vibration ; Young Adult

We evaluated the role of IL-10- in IL-33-mediated cholesterol reduction in macrophage-derived foam cells (MFCs) and the mechanism by which IL-33 upregulates IL-10. Serum IL-33 and IL-10 levels in coronary artery disease patients were measured. The effects of IL-33 on intra-MFC cholesterol level, IL-10, ABCA1 and CD36 expression, ERK 1/2, Sp1, STAT3 and STAT4 activation, and IL-10 promoter activity were determined. Core sequences were identified using bioinformatic analysis and site-specific mutagenesis. The serum IL-33 levels positively correlated with those of IL-10. IL-33 decreased cellular cholesterol level and upregulated IL-10 and ABCA1 but had no effect on CD36 expression. siRNA-IL-10 partially abolished cellular cholesterol reduction and ABCA1 elevation by IL-33 but did not reverse the decreased CD36 levels. IL-33 increased IL-10 mRNA production but had little effect on its stability. IL-33 induced ERK 1/2 phosphorylation and increased the luciferase expression driven by the IL-10 promoter, with the highest extent within the −2000 to −1752 bp segment of the 5′-flank of the transcription start site; these effects were counteracted by U0126. IL-33 activated Sp1, STAT3 and STAT4, but only the STAT3 binding site was predicted in the above segment. Site-directed mutagenesis of the predicted STAT3-binding sites (CTGCTTCCTGGCAGCAGAA→CTGCCTGGCAGCAGAA) reduced luciferase activity, and a STAT3 inhibitor blocked the regulatory effects of IL-33 on IL-10 expression. Chromatin immunoprecipitation (CHIP) confirmed the STAT3-binding sequences within the −1997 to −1700 and −1091 to −811 bp locus regions. IL-33 increased IL-10 expression in MFCs via activating ERK 1/2 and STAT3, which subsequently promoted IL-10 transcription and thus contributed to the beneficial effects of IL-33 on MFCs.
Binding Sites ; Cholesterol ; Chromatin Immunoprecipitation ; Computational Biology ; Coronary Artery Disease ; Foam Cells* ; Humans ; Interleukin-10* ; Interleukin-33* ; Luciferases ; Macrophages* ; Mutagenesis, Site-Directed ; Phosphorylation ; RNA, Messenger ; Transcription Initiation Site

Objective To evaluate the population health for disease prevention and control in Shanghai Minhang District of Shanghai the data of mortality from 1993 to 2015 and communicable diseases from 2002 to 2015.Methods We adopted descriptive epidemiological method to analyze the trends of average life expectancy (ALE),specific death rate and causes of death cis-position from 1993 to 2015,and the incident rates of communicable diseases,incidence trends in Minhang District from 2002 to 2015.Results Overall,the ALE of population in Minhang District increased 11.80 years from 1993 to 2015 (from 71.78 years in 1993 to 83.58 years in 2015),including the ALE of male population increased 14.03 years (from 67.43 years in 1993 to 81.37 years in 2015) and the ALE of female population elevated 9.67 years (from 76.22 years in 1993 to 85.89 years in 2015).In 2015,Crude death rate (CDR) was 755.35/105,which was 21.45％ higher than in 1993 and 2.71％ higher than in 2014,respectively.In the same year,standardized mortality rate (SMR) was 196.07/105,which was 54.17％ lower than in 1993 and 0.51％ lower than in 2014.The top five leading causes of death were circulatory system diseases,tumors,respiratory diseases,endocrine and metabolic diseases,and injury and poisoning,which contributed 91.33％ of the population death.From 2002 to 2015,a total of 23 kinds of notifiable infectious diseases were reported in Minhang District,including 62 845 cumulative cases and 152 cases died.The total reported incidence rate of communicable diseases sharply elevated by 291.98％ during 14 years (Z=10 943.83,P＜0.001),and it increased after standardized.The top five communicable diseases were hand foot and mouth disease (HFMD),scarlet fever,syphilis,tuberculosis and hepatitis B in 2015.Conclusions Over the years,Minhang District of Shanghai comprehensive implemented "health in all policies" by integrating the resources of all levels of regional healthcare institutions.The ALE of the residents was at a high level.The control and prevention of chronic non-communicable diseases and major communicable diseases will continue to be the priority of public health.

Objective To evaluate the diagnostic value of contrast-enhanced ultrasound in breast precancerous lesions . Methods Retrospectively analyzed the contrast-enhanced ultrasound model and angiographic predictive model of 465 cases of the A prospective multicenter study of breast nodules contrast-enhanced ultrasound" that led the Sichuan Provincial People′s Hospital from January 2016 to April 2017 ,which included 69 cases of breast precancerous lesions and 396 other types benign lesions ,and the sensitivity ,specificity and accuracy of the diagnosis of breast precancerous lesions were calculated . Results The sensitivity of ultrasound predictive model for the diagnosis of precancerous lesions was 60 .9％ and AUC was 0 .681 . Precancerous lesions mainly showed non-concentricity , increased homogeneity , and increased lesions;other types of benign lesions mainly showed non-centripetal ,high uniformity enhancement and lesion size unchanged . Conclusions Contrast-enhanced ultrasound shows a potential value in the differential diagnosis of precancerous lesions and other types of benign lesions ,that can help clinicians to take early intervention measures for breast precancerous lesions ,but there are still many problems to be solved .