简介：AbstractObjective:To build a reference fetal growth chart for the Chinese population based on fetal ultrasound measurements.Methods:This was a multicenter, population-based retrospective cohort study. Longitudinal ultrasound measurement data were collected from 24 hospitals in 18 provinces of China from 1st September through 31st October of 2019. The estimated fetal weight (EFW) was calculated based on head circumference, abdominal circumference, and femur length using Hadlock formula 3. Fetal growth curves were estimated using a two-level linear regression model with cubic splines. All participants were divided into two groups: the northern group (n = 5829) and the southern group (n = 3246) based on the geographical division of China and male fetus group (n = 4775) and female fetus group (n = 4300) based on fetal gender. The EFW was compared by fetal gender and geographical group. All statistical models were adjusted for maternal sociodemographic characteristics.Results:A total of 9075 participants with 31,700 ultrasound measurement records were included in this study. Male fetuses demonstrated significantly larger EFW compared to female ones starting at 16 weeks of gestation and extending to delivery (global test P < 0.01). The overall geographic difference in EFW was significant (global test P = 0.03), and week-specific comparisons showed that the northern group had a greater EFW starting at 15 weeks of gestation and extending to 29 weeks of gestation, although this difference did not extend to the time of delivery. The Z-score of EFW confirmed that our Chinese fetal growth charts differed from previously published standards.Conclusion:This study provides EFW and ultrasound biometric reference measurements for Chinese fetuses and reveals differences from other fetal growth charts. The chart is worth promoting in more regions of China but should be tested prudently before use.

简介：AbstractBackground:Dengue is the fastest spreading arboviral disease, posing great challenges on global public health. A reproduceable and comparable global genotyping framework for contextualizing spatiotemporal epidemiological data of dengue virus (DENV) is essential for research studies and collaborative surveillance.Methods:Targeting DENV-1 spreading prominently in recent decades, by reconciling all qualified complete E gene sequences of 5003 DENV-1 strains with epidemiological information from 78 epidemic countries/areas ranging from 1944 to 2018, we established and characterized a unified global high-resolution genotyping framework using phylogenetics, population genetics, phylogeography, and phylodynamics.Results:The defined framework was discriminated with three hierarchical layers of genotype, subgenotype and clade with respective mean pairwise distances 2-6%, 0.8-2%, and ≤ 0.8%. The global epidemic patterns of DENV-1 showed strong geographic constraints representing stratified spatial-genetic epidemic pairs of Continent-Genotype, Region-Subgenotype and Nation-Clade, thereby identifying 12 epidemic regions which prospectively facilitates the region-based coordination. The increasing cross-transmission trends were also demonstrated. The traditional endemic countries such as Thailand, Vietnam and Indonesia displayed as persisting dominant source centers, while the emerging epidemic countries such as China, Australia, and the USA, where dengue outbreaks were frequently triggered by importation, showed a growing trend of DENV-1 diffusion. The probably hidden epidemics were found especially in Africa and India. Then, our framework can be utilized in an accurate stratified coordinated surveillance based on the defined viral population compositions. Thereby it is prospectively valuable for further hampering the ongoing transition process of epidemic to endemic, addressing the issue of inadequate monitoring, and warning us to be concerned about the cross-national, cross-regional, and cross-continental diffusions of dengue, which can potentially trigger large epidemics.Conclusions:The framework and its utilization in quantitatively assessing DENV-1 epidemics has laid a foundation and re-unveiled the urgency for establishing a stratified coordinated surveillance platform for blocking global spreading of dengue. This framework is also expected to bridge classical DENV-1 genotyping with genomic epidemiology and risk modeling. We will promote it to the public and update it periodically.

简介：AbstractImportance:In cases of epiblepharon with lower eyelid retraction secondary to glaucoma, correcting epiblepharon alone is ineffective. Combined surgery should be performed to obtain satisfactory outcomes.Objective:To investigate outcomes after surgery to correct epiblepharon with lower eyelid retraction secondary to buphthalmos in children.Methods:A retrospective analysis of six eyes in four patients was performed included lower lid retractor recession combined with marginal rotation with tarsal fixation. The margin reflex distance-2, lagophthalmus, resolution of clinical symptoms, and complications were assessed during 6 to 12 months of follow-up.Results:In all cases, epiblepharon and lagophthalmus were corrected, symptoms of photophobia and epiphora were relieved, and the corneal epithelium was repaired. The margin reflex distance-2 decreased and remained normal during the follow-up period, but slightly regressed within 6 months postoperatively.Interpretation:Epiblepharon caused by buphthalmos in children is often associated with lower eyelid retraction. Lower lid retractor recession combined with marginal rotation with tarsal fixation fundamentally solves the problems of high eyelid tension, lower eyelid retraction, and epiblepharon and reduces the recurrence rate.

简介：AbstractBackground:Empiric therapy for patients with unexplained recurrent pregnancy loss (URPL) is not precise. Some patients will ask for assisted reproductive technology due to secondary infertility or advanced maternal age. The clinical outcomes of URPL patients who have undergone in vitro fertilization-embryo transfer (IVF-ET) require elucidation. The IVF outcome and influencing factors of URPL patients need further study.Methods:A retrospective cohort study was designed, and 312 infertile patients with URPL who had been treated during January 2012 to December 2015 in the Reproduction Center of Peking University Third Hospital were included. By comparing clinical outcomes between these patients and those with tubal factor infertility (TFI), the factors affecting the clinical outcomes of URPL patients were analyzed.Results:The clinical pregnancy rate (35.18% vs. 34.52% in fresh ET cycles, P = 0.877; 34.48% vs. 40.27% in frozen-thawed ET cycles, P = 0.283) and live birth rate (LBR) in fresh ET cycles (27.67% vs. 26.59%, P = 0.785) were not significantly different between URPL group and TFI group. URPL group had lower LBR in frozen-thawed ET cycles than that of TFI group (23.56% vs. 33.56%, P = 0.047), but the cumulative LBRs (34.69% vs. 38.26%, P = 0.368) were not significantly different between the two groups. The increased endometrial thickness (EMT) on the human chorionic gonadotropin day (odds ratio [OR]: 0.848, 95% confidence interval [CI]: 0.748-0.962, P = 0.010) and the increased number of eggs retrieved (OR: 0.928, 95% CI: 0.887-0.970, P = 0.001) were protective factors for clinical pregnancy in stimulated cycles. The increased number of eggs retrieved (OR: 0.875, 95% CI: 0.846-0.906, P < 0.001), the increased two-pronucleus rate (OR: 0.151, 95% CI: 0.052-0.437, P < 0.001), and increased EMT (OR: 0.876, 95% CI: 0.770-0.997, P = 0.045) in ET day were protective factors for the cumulative live birth outcome.Conclusion:After matching ages, no significant differences in clinical outcomes were found between the patients with URPL and the patients with TFI. A thicker endometrium and more retrieved oocytes increase the probability of pregnancy in fresh transfer cycles, but a better normal fertilization potential will increase the possibility of a live birth.

简介：AbstractObjectives:Mechanistic target of rapamycin (mTOR) activation has been identified in keloid. This study aimed to identify the role of mTOR-dependent autophagy activity in keloid.Methods:We detected the expression of specific proteins representing mTOR activity and baseline autophagy levels in keloid tissues (KTs) and primary keloid fibroblasts (KFs) using immunohistochemical staining and western blotting. Simultaneously, the formation of acid vesicles was assessed by acridine orange staining in KFs. To investigate whether mTOR-dependent pathway mediated the regulation of autophagy machinery in keloid, we first validated whether mTOR inhibitors, rapamycin (100 nmol/L) and KU-0063794 (5 μmol/L), could inhibit mTOR activity in KFs by western blotting. Then we explored the reverse effects on autophagy activity induced by mTOR inhibitors in the presence of lysosomal protease inhibitors by western blotting.Results:It demonstrated elevated expression of mTOR, S6, and their activated forms in KTs, and an elevated expression of p-S6 Ser235/236 in KFs, suggesting mTOR was activated in keloid. Less LC3 and Beclin1 were expressed in the cytoplasm of KFs, whereas Ubiquitin was abundantly expressed in KTs compared with extra-lesional tissues. In addition, at the cellular level, an impeded conversion of LC3-I to LC3-II was shown in KFs and the formation of acid vesicles were also decreased in KFs compared with normal fibroblasts (NFs), indicating that autophagy activity is defective in keloid. mTOR inhibitors, Rapamycin (E-64d + pepstatin vs. rapamycin + E-64d + pepstatin: [0.88 ± 0.35] vs. [1.56 ± 0.46], F= 5.56, P= 0.049) and KU-0063794 (E-64d + pepstatin vs. KU-0063794 + E-64d + pepstatin: [0.92 ± 0.22] vs. [1.51 ± 0.25], F= 25.88, P= 0.011) can reverse the inhibition effect on autophagy of KFs while inhibiting mTOR activity.Conclusion:Autophagy machinery is inhibited in keloid which is regulated by mTOR-dependent pathway.

简介：AbstractObjective:The plant polyphenol resveratrol (3,4′,5-trihydroxystilbene) (RSV) has been proposed for use because of its protective effect on ultraviolet (UV)-induced skin disorders. In UVB-induced skin damage, cell autophagy and apoptosis have been approved to prevent the damage and to contribute to the cytoprotective role of RSV; however, the detailed mechanism remains unknown. So, we conducted this study to investigate the cytoprotective effects of RSV on UVB-irradiated human epidermal keratinocytes (HEKs) and its undergoing mechanisms.Methods:Secretion of thirty-six inflammatory cytokines of HEKs induced by 50 mJ/cm2 UVB at 0, 12, 24, and 48 hours were detected by a human cytokine assay and the interleukin (IL)-8 protein level in the culture media were determined by ELISA. Next, HEKs were treated with or without 100 μmol/L RSV in the presence or absence of 50 mJ/cm2 UVB, and activator protein 1 and NF-κB-related proteins were measured by Western blot. Furthermore, cells exposed to UVB radiation were treated with apoptosis activators procaspase-activating compound 1 (PAC-1), apoptosis activator 2 (AA2) or RSV to investigate the effect of RSV on the percentage of apoptotic cells by flow cytometry. Then cells were treated with autophagy inhibitors LY294002, 3-methyladenine (3-MA) or RSV in the presence of UVB and chloroquine (CQ) to investigate the effect of RSV on autophagy through detecting microtubule-associated protein 1 light chain 3 (LC3) expression by western blot. Finally, the effect of LY294002, 3-MA, ATG5 siRNA, PAC-1, and AA2 on RSV-mediated reduction of IL-8 expression was determined by ELISA assay.Results:RSV treatment decreased the secretion of IL-8 (UVB vs. UVB+ RSV: [1454.05 pg/mL ± 52.95 pg/mL] vs. [553.68 pg/mL ± 206.03 pg/mL], P < 0.001), and downregulated the protein level of c-Fos in UVB-irradiated HEKs (UVB vs. UVB+ RSV: [0.103 ± 0.009] vs. [0.048 ± 0.015], P < 0.01). In UVB-irradiated HEKs, the result of western blot showed that LY294002 and 3-MA inhibited RSV-induced LC3 II accumulation (UVB + CQ + RSV vs. UVB + CQ + 3-MA+ RSV vs. UVB + CQ + LY294002+ RSV: [1.15 ± 0.03] vs. [0.77 ± 0.13] vs. [0.67 ± 0.13], P < 0.01), and the result of flow cytometry showed that PAC-1 and AA2 prevented RSV from reducing cell apoptosis (UVB+ RSV vs. UVB+ PAC-1 + RSV vs. UVB+ AA2+ RSV: [19.56% ± 0.62%] vs. [94.33% ± 0.15%] vs. [94.97% ± 1.91%], P < 0.001). The data of ELSA assay showed that LY294002, 3-MA, and ATG5 siRNA reversed the RSV-mediated inhibition of IL-8 protein secretion by UVB-irradiated HEKs (UVB + LY294002 vs. UVB + LY294002 + RSV: [3283.00 pg/mL ± 444.05 pg/mL] vs. [1608.58 pg/mL ± 128.42 pg/mL], P < 0.05; UVB + 3-MA vs. UVB+ 3-MA+ RSV: [2941.88 pg/mL ± 103.80 pg/mL] vs. [1867.51 pg/mL ± 153.84 pg/mL], P < 0.01; UVB+ siATG5 vs. UVB+ siATG5+ RSV: [2530.11 pg/mL ± 685.34 pg/mL] vs. [3011.42 pg/mL ± 435.69 pg/mL], P > 0.05), whereas neither PAC-1 nor AA2 exerted similar effects.Conclusion:RSV may regulate autophagic flux to inhibit IL-8 expression in UVB-challenged keratinocytes.

简介：AbstractPurpose:This research examined road traffic injury mortality and morbidity disparities across of country development status, and discussed the possibility of reducing country disparities by various actions to accelerate the pace of achieving Sustainable Development Goals target 3.6 - to halve the number of global deaths and injuries from road traffic accidents by 2020.Methods:Data for road traffic mortality, morbidity, and socio-demographic index (SDI) were extracted by country from the estimates of the Global Burden of Disease study, and the implementation of the three types of national actions (legislation, prioritized vehicle safety standards, and trauma-related post-crash care service) were extracted from the Global Status Report on Road Safety by World Health Organization. We fitted joinpoint regression analysis to identify and quantify the significant rate changes from 2011 to 2017.Results:Age-adjusted road traffic mortality decreased substantially for all the five SDI categories from 2011 to 2017 (by 7.52%-16.08%). Age-adjusted road traffic mortality decreased significantly as SDI increased in the study time period, while age-adjusted morbidity generally increased as SDI increased. Subgroup analysis by road user yielded similar results, but with two major differences during the study period of 2011 to 2017: (1) pedestrians in the high SDI countries experienced the lowest mortality (1.68-1.90 per 100,000 population) and morbidity (110.45-112.72 per 100,000 population for incidence and 487.48-491.24 per 100,000 population for prevalence), and (2) motor vehicle occupants in the high SDI countries had the lowest mortality (4.07-4.50 per 100,000 population) but the highest morbidity (428.74-467.78 per 100,000 population for incidence and 1025.70-1116.60 per 100,000 population for prevalence). Implementation of the three types of national actions remained nearly unchanged in all five SDI categories from 2011 to 2017 and was consistently stronger in the higher SDI countries than in the lower SDI countries. Lower income nations comprise the heaviest burden of global road traffic injuries and deaths.Conclusion:Global road traffic deaths would decrease substantially if the large mortality disparities across country development status were reduced through full implementation of proven national actions including legislation and law enforcement, prioritized vehicle safety standards and trauma-related post-crash care services.

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简介：AbstractPemphigus vulgaris (PV) is a life-threatening autoimmune bullous disease that causes blisters and erosions on the skin and mucous membranes to standardize the diagnosis and treatment of PV, Chinese experts in this field were invited to make recommendations which are presented in this article. Pemphigus vulgaris can be divided into cutaneous mucous type, cutaneous type and mucous mucous dominant type according to the different clinical manifestations. The pathological manifestations of PV are acantholysis above the basal layer. The diagnosis of PV and the assessment of the severity of the disease are made in accordance with the clinical manifestations, histopathological features, immunofluorescence assay results, and detection of pathogenic serum antibodies. The first-line treatment of PV comprises systemic glucocorticoids. Early combination with immunosuppressive agents or rituximab is recommended for moderate and severe PV. Intravenous immunoglobulin administration is recommended for patients being treated with rituximab. Plasma exchange and stem cell transplantation can be performed if necessary. During the course of therapy, the disease activity should be closely monitored, and actions should be taken to prevent adverse reactions.

简介：AbstractObjective:In contrast to the most commonly reported forms of maturity-onset diabetes of the young (MODY), including MODY2, MODY3 and MODY5, MODY6 is a relatively rare subtype. To investigate whether NEUROD1 is responsible for MODY in Chinese individuals, we screened its mutations in MODY pedigrees and explored the potential pathogenic mechanisms.Methods:Polymerase chain reaction direct sequencing was performed to screen NEUROD1 mutations in 32 Chinese MODY probands who were negative for the GCK/MODY2, HNF1A/MODY3 and HNF1B/MODY5 genes in this observational study. In addition, we enrolled 201 unrelated, non-diabetic control subjects of Han Chinese descent. The functional significance of newly identified mutations was analyzed using clinical phenotype, pathophysiology and three-dimensional structure studies. This study was approved by the Institutional Review Board of Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, China (approval No. YS-2017-83) on March 3, 2017.Results:E59Q (c.175 G>C, p.Glu59Gln), a heterozygous missense mutation in the NEUROD1 gene, was identified in one family with MODY. The Glu59 residue in NeuroD1 is highly conserved across mammalian species. Four diabetic patients carrying the mutation (a proband and her son, brother and sister) were lean, with a body mass index of 20.9 (20.3-21.2) kg/m2. Compared with their unaffected relatives (n= 4), E59Q carriers (n= 4) had significantly decreased ratios of fasting and 2-hour insulin to plasma glucose (both fasting plasma insulin/fasting plasma glucose and 2-hour postprandial plasma insulin/2-hour postprandial plasma glucose, P < 0.005). The proband’s father had an E59Q mutation and normal glucose tolerance, which suggested non-penetrance. The E59Q mutation was not detected in other probands or in the 201 control subjects with normal glucose tolerance. Two salt-bridge bonds of Glu59 were disrupted at the Q59 mutation site.Conclusion:The NEUROD1-E59Q mutation changed the molecular conformation of the N-terminal in NeuroD1, which may decrease binding of the E59Q mutant to the insulin promoter and insulin gene transcription activity, therefore causing the MODY6 subtype with defective insulin secretion.

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简介：AbstractBackground:Human infections with zoonotic coronaviruses (CoVs), including severe acute respiratory syndrome (SARS)-CoV and Middle East respiratory syndrome (MERS)-CoV, have raised great public health concern globally. Here, we report a novel batorigin CoV causing severe and fatal pneumonia in humans.Methods:We collected clinical data and bronchoalveolar lavage (BAL) specimens from five patients with severe pneumonia from Wuhan Jinyintan Hospital, Hubei province, China. Nucleic acids of the BAL were extracted and subjected to next-generation sequencing. Virus isolation was carried out, and maximum-likelihood phylogenetic trees were constructed.Results:Five patients hospitalized from December 18 to December 29, 2019 presented with fever, cough, and dyspnea accompanied by complications of acute respiratory distress syndrome. Chest radiography revealed diffuse opacities and consolidation. One of these patients died. Sequence results revealed the presence of a previously unknown β-CoV strain in all five patients, with 99.8% to 99.9% nucleotide identities among the isolates. These isolates showed 79.0% nucleotide identity with the sequence of SARS-CoV (GenBank NC_004718) and 51.8% identity with the sequence of MERS-CoV (GenBank NC_019843). The virus is phylogenetically closest to a bat SARS-like CoV (SL-ZC45, GenBank MG772933) with 87.6% to 87.7% nucleotide identity, but is in a separate clade. Moreover, these viruses have a single intact open reading frame gene 8, as a further indicator of bat-origin CoVs. However, the amino acid sequence of the tentative receptor-binding domain resembles that of SARS-CoV, indicating that these viruses might use the same receptor.Conclusion:A novel bat-borne CoV was identified that is associated with severe and fatal respiratory disease in humans.

简介：AbstractObjective:This study was aimed to determine the changes in CXCR2 expression in preeclampsia placenta and its correlation with clinical parameters.Methods:Sixty-four gravidas ranging in age from 25 to 42 years referred to the obstetrics unit of the West China Second University Hospital from April 2012 to October 2012 were recruited in this case-control study; women were diagnosed and divided into early-onset preeclampsia group (n= 22), late-onset preeclampsia group (n= 22), and healthy pregnancy group (n= 20). After immunolocalized in human placenta, the levels of CXCR2 protein and messenger ribonucleic acid (mRNA) were detected by enzyme-linked immunosorbent assay and real-time quantitative polymerase chain reaction. Correlations between placental CXCR2 protein expression with systolic blood pressure and lactate dehydrogenase (LDH) in early-onset preeclampsia were examined using Pearson or Spearman’s correlation coefficients.Results:Placental CXCR2 protein and mRNA expression in early-onset preeclampsia was significantly lower than it was in placentas from healthy pregnancy pregnancies and late-onset preeclampsia (P < 0.05). The placental CXCR2 protein expression correlated negatively with systolic blood pressure and LDH in early-onset preeclampsia (r= -0.51, P < 0.05; r=-0.43, P < 0.05).Conclusion:Significant abnormal placental CXCR2 expression in early-onset preeclampsia, and its correlations with some clinical parameters (systolic blood pressure and LDH) were discovered, suggesting that CXCR2 may play a role in the pathogenesis of early-onset preeclampsia.

简介：AbstractBackground:Regulatory policy (RP) is known as a major factor to improve health care system performance. A significant difference in maternal mortality rates (MMRs) was observed between New York city (NYC) and Shanghai (SH), both first-class international metropolises. This study aims to adopt a quantitative evaluation model to analyze whether RP differences contribute to the different MMRs of the two cities.Methods:Based on collection of all publicly released policy documents regarding maternal health in the two cities, we assessed and compared the status of their maternal health care RPs from 2006 to 2017 through a series of quantitative indicators as regulatory elements coverage rate (RECR), departmental responsibility clarity rate (DRCR), and accountability mechanism clarity rate (AMCR), based on two characteristics of comprehensiveness and effectiveness of RPs. Pearson correlation analysis, principal component analysis, and linear regression analysis were used to test the relationships between the indicators and MMR in SH and NYC.Results:By 2017, disparities of maternal health care RP are found between SH and NYC, from the indicators of RECR (100% vs. 77.0%), DRCR (38.9% vs. 45.1%), and AMCR (29.2% vs. 22.5%). From 2006 to 2017, RECR, DRCR, and AMCR in SH have shown a higher growth of 8.7%, 53.2%, and 45.2%, compared with growth of 25.0%, 12.5%, and 2.9% in NYC. The three indicators were found all negatively correlated with MMR in SH (Coefficients = －0.831, －0.833, and －0.909, and P < 0.01), while only RECR and DRCR had negative correlation with MMR in NYC (Coefficients = －0.736 and －0.683, and P < 0.05). Linear regression showed that the principal components of the three indicators were found with significant impact on MMRs both in SH (R = 0.914, R2 = 0.836, P < 0.001) and NYC (R = 0.854, R2 = 0.357, P = 0.04).Conclusion:Compared with NYC, the more comprehensive and effective maternal health care RPs in SH had a stronger impact on MMR control, which contributed to the differences between the two cities’ MMRs to some extent. The methods and indicators we adopted for assessment are reasonable and comparable.