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Innovation and entrepreneurship are important driving forces for economic growth, and the Internet plays an essential role in entrepreneurship activities. This paper studies the impact of the Internet on entrepreneurship and its mechanism by using China Family Panel Studies (CFPS) dataset in 2014 and 2016. Our empirical findings indicate that the Internet has a significant and positive influence on entrepreneurship, and the results remain robust even after addressing endogeneity. Moreover, heterogeneous examinations suggest that the Internet is more beneficial for opportunistic entrepreneurship and in rural areas. Further mechanism analysis shows that the Internet promotes entrepreneurship mainly through facilitating entrepreneurs to access information and helping entrepreneurs obtain informal financing.

Diabetic nephropathy (DN) is still on the rise worldwide, and millions of patients have to be treated through dialysis or transplant because of kidney failure caused by DN. Recent reports have highlighted circRNAs in the treatment of DN. Herein, we aimed to investigate the mechanism by which high glucose‐induced exo‐circ_0125310 promotes diabetic nephropathy progression. circ_0125310 is highly expressed in diabetic nephropathy and exosomes isolated from high glucose‐induced mesangial cells (MCs). High glucose‐induced exosomes promote the proliferation and fibrosis of MCs. However, results showed that the effects of exosomes on MCs can be reversed by the knockdown of circ_0125310. miR‐422a, which targets IGF1R, was the direct target of circ_0125310. circ_0125310 regulated IGF1R/p38 axis by sponging miR‐422a. Exo‐circ_0125310 increased the luciferase activity of the WT‐IGF1R reporter in the dual‐luciferase reporter gene assays and upregulated the expression level of IGF1R and p38. Finally, in vivo research indicated that the overexpression of circ_0125310 promoted the diabetic nephropathy progression. Above results demonstrated that the high glucose‐induced exo‐circ_0125310 promoted cell proliferation and fibrosis in diabetic nephropathy via sponging miR‐422a and targeting the IGF1R/p38 axis.

We describe a scheme for generation of spatial-mode-entangled photon pairs in a few-mode fiber and experimentally demonstrate generation of idler beams from classical seed signals representing various superpositions of fiber LP01 and LP $_{11a}$ modes. For every signal mode superposition, we observe the indication of idler mode orthogonality to the signal mode.

We present a scheme for spatial-mode-selective frequency conversion in a few-mode fiber and experimentally demonstrate upconversion of arbitrary superpositions of LP01 and LP11a signal modes from C-band to the fundamental mode in S-band with all conversion efficiencies within 1 dB range of one another.

BACKGROUND: Oral squamous cell carcinoma (OSCC) usually originates from oral potentially malignant disorders (OPMD), such as oral leukoplakia (OLK) and oral lichen planus (OLP). Identifying biomarkers for the early diagnosis and evaluation of malignant transformation in OPMD could improve the survival rate of OSCC patients. OBJECTIVE: The present study aimed to screen for potential salivary biomarkers for evaluating the malignant transformation of OPMD. METHODS: Salivary proteases from OLK and OSCC patients or healthy donors and proteases in cultural medium from DOK and Cal-27 cells were detected with a human protease array kit. The concentrations of the salivary Kallikrein 5 (KLK5) and urokinase-type plasminogen activator (uPA) proteases were measured by ELISA. Receiver operating characteristics (ROC) to determine the potential value of these proteases in clinical diagnosis were calculated using SPSS software. Immunohistochemistry was used to detect the KLK5 and uPA expression in the oral organizations. RESULTS: The salivary protease spectrum was different among patients with OLK and OSCC and healthy donors. KLK5 and uPA levels in saliva tended to increase as the disease progressed (healthy < OPMD [OLK and OLP] < OSCC). ROC curves showed the optimum diagnostic cutoffs for KLK5 as a biomarker for OLK, OLP, and OSCC were 5.97, 6.03, and 9.45 pg/mL, respectively, while the cutoffs for uPA were 17.19, 17.26, and 20.96 pg/mL. Their combined analysis showed a higher sensitivity for the differential diagnosis of disease. Furthermore, higher levels of KLK5 and uPA were observed in OSCC tissues than in OLK and OLP. CONCLUSIONS: Salivary KLK5 and uPA are potential biomarkers for evaluating OLK and OLP malignant transformation and early diagnosis of OSCC.

Background The standard management for upper urinary tract urothelial carcinoma (UTUC) is radical nephroureterectomy (RNU). However, some patients cannot undergo this procedure for several reasons, such as unresectable disease, old age, and multiple comorbidities. Our study explored the potential safety and effectiveness of radiotherapy as a curative treatment for UTUC patients unfit for surgery. Methods The data of patients treated with radiotherapy between December 2017 and November 2019 were retrospectively reviewed. For the literature review, computerized PubMed Medline, Index Medicus, and Web of Science databases and reference lists from the identified publications of interest were used. And "upper-tract urothelial carcinoma" and "radiotherapy" were used as key words in the search. Results We describe 8 patients with UTUC who were treated with radiotherapy. The median follow-up time was 13.5 months (range, 8.6-30.9 months). Local tumor control was achieved in all patients. However, distant metastases were observed in 2 patients with T3-4/N+ status. One patient had T4 status and the other had N2+ status. The patients died of tumor progression at 15.0 and 17.7 months. In addition, the other 6 patients who were still alive had relatively early-stage tumors without nodal involvement. Regarding acute toxicity, according to the CTCAE v5.0, mild side effects were noted, including grade 1 nausea and diarrhea. Four patients developed mild anemia, generally of grade 1-2. One patient experienced grade 3 anemia, but it was manageable and improved with symptomatic support. In addition, no grade 4 acute or late toxicities were observed. No significant long-term impairment of renal function occurred. Conclusions For patients with nonmetastatic UTUC who are not suitable for surgery, radiotherapy is a safe treatment and can achieve good local tumor control.

Objectives Air pollution can lead to many cardiovascular and respiratory diseases, but the impact of air pollution on pulmonary embolism is still uncertain. We conducted a meta-analysis to assess the relationship between air pollution and pulmonary embolism. Content We searched PubMed, EMBASE, Web of Science, and the Cochran Library for citations on air pollutants (carbon monoxide, sulfur dioxide, nitrogen dioxide, ozone and particulate matter) and pulmonary embolism. A total of nine citations met the inclusion criteria. There is no evidence of bias. CO, SO2, PM10 and PM2.5 had no significant effect on the occurrence of pulmonary embolism. NO2 and O3 can increase the risk of pulmonary embolism to a small extent. Summary This meta-analysis suggests that some air pollutants are associated with an increased risk of pulmonary embolism. Outlook Reducing air pollution and improving air quality can effectively reduce the risk of pulmonary embolism.

In this study, we established a mouse model of epilepsy and analysed abnormal neuronal damage and inflammation in the hippocampus of mice with kainic acid (KA)-induced epilepsy to provide the basis for the pathogenesis of epilepsy. C57 mice, aged 4 weeks, were injected intraperitoneally in the KA group with 20 mg/kg of KA and in the sham experimental group with normal saline. The whole brain and hippocampus of mice in the sham experimental group and KA epilepsy model group were collected on days 7, 14, 21 and 28 after injection. The difference in the protein expression in the hippocampus was detected using fluorescence immunohistochemistry. The hippocampal tissue was also collected and frozen to detect protein expression by western blot. The results of the haematoxylin and eosin (HE) and Nissl staining showed that the mouse model of temporal lobe epilepsy could be established by intraperitoneal injection of KA, and the success rate of the model was 53.8%. The expression of DCX-, β-catenin-, GFAP- and Iba-1-labelled glial cells in the KA-induced epilepsy model group were higher than those in the sham group. The results of western blotting showed that the expression of DCX and β-catenin in the KA-induced epilepsy model group was higher than that in the sham experimental group, while the expression of N-cadherin and Iba-1 on days 14 and 28 was significantly (P < .05) higher than that in the sham experimental group. In KA-induced epilepsy model group, the expression of Bcl-2 was decreased, while the expression of Bad and PUMA was increased.

Chronic kidney disease is a global health problem and eventually develops into an end-stage renal disease (ESRD). It is now widely believed that renal tubulointerstitial fibrosis (TIF) plays an important role in the progression of ESRD. Renal tubular epithelial-mesenchymal transition (EMT) is an important cause of TIF. Studies have shown that FGF2 is highly expressed in fibrotic renal tissue, although the mechanism remains unclear. We found that FGF2 can activate STAT3 and induce EMT in renal tubular epithelial cells. STAT3, an important transcription factor, was predicted by the JASPAR biological database to bind to the promoter region of YAP1. In this study, STAT3 was shown to promote the expression of the downstream target gene YAP1 through transcription, promote EMT of renal tubular epithelial cells, and mediate the occurrence of renal TIF. This study provides a theoretical basis for the involvement of the FGF2/STAT3/YAP1 signaling pathway in the process of renal interstitial fibrosis and provides a potential target for the treatment of renal fibrosis.

Amebiasis is a disease caused by the protozoan parasite Entamoeba histolytica, which mainly shows symptoms of acute diarrhea, dysentery, amebic colitis, and amebic liver abscesses. As the fourth leading parasitic cause of human mortality, E. histolytica mainly infect children in developing countries, transmitted by food and water contamination. In the majority of infected individuals, Entamoeba sp. asymptomatically colonizes the large intestine and self-limiting, while in others, the parasite breaches the mucosal epithelial barrier to cause amebic colitis and can disseminate to soft organs to cause abscesses. Metronidazole (MTZ) is the recommended and most widely used drug for treating the invasive amebiasis. No amebiasis vaccine has been approved for human clinical trials to date, but many recent vaccine development studies hold promise. For the prevention and control of amebiasis, improvement of water purification systems and hygiene practices could decrease disease incidence. In this review, we focus on the epidemiology, transmission, clinical signs, pathogenesis, diagnosis, treatment, prevention and control of the zoonotic amebiasis.

Despite novel therapeutic options, many people with type 2 diabetes (T2D) do not achieve their HbA1c targets. Given the progressive nature of T2D, many individuals not controlled with oral therapy will require advancement to injectable therapy using either a glucagon‐like peptide‐1 receptor agonist (GLP‐1 RA), recently recommended as a first option, or traditionally a basal insulin. However, premix insulins remain frequently used, either as initial injectable therapy or as intensification from basal insulin. Premix insulin injections can potentially provide significant glycaemic improvements to basal insulin but at the expense of increased hypoglycaemia and weight gain and the need for multiple daily doses, which may affect treatment adherence. Real‐world evidence suggests that glycaemic control often remains suboptimal with premix insulins. Fixed‐ratio combinations (FRCs) of basal insulin and GLP‐1 RAs provide a novel alternative to premix insulin for therapy intensification. While no direct comparisons between premix insulins and FRCs are available, results from meta‐analyses suggest that FRCs may offer better HbA1c reductions, a lower risk of hypoglycaemia and less weight gain compared with premix insulin in a simplified treatment regimen. A head‐to‐head trial of T2D treatment intensification with premix insulin and a FRC of basal insulin plus a GLP‐1 RA is currently in progress, which should help to clarify the outcomes for each treatment option. This review discusses the unmet needs of people with T2D treated with premix insulin and provides evidence supporting FRCs of basal insulin and GLP‐1 RAs as an alternative treatment option.

PurposeNeglecting to wear a safety helmet can result in serious injuries at construction sites, but the cause of such unsafe behavior has not been fully understood. Therefore, the purpose of this paper is to provide a means of systematically understanding on the causes of non-helmet use behaviors at construction sites.Design/methodology/approachThis paper utilizes the system dynamics (SD) modeling to portray the construction system works at project, management and individual levels to understand the relative importance of safety climate and productivity pressures. A real-time helmet use behavior tracking system (the Eye on Project (EOP)) is developed to provide an objective record of helmet use practices. Using the data collected from the EOP, the proposed SD model can be calibrated to simulate the influence of safety climate and productivity pressures on the non-helmet use behaviors of construction workers.FindingsThe data collected from 91 responses through the questionnaire survey were utilized to develop the SD model, which consists of two balancing loops and two reinforced loops. The mean absolute percentage error is further used to evaluate the model. The results show that a positive safety climate significantly reduced the rate of non-helmet use behavior.Originality/valueThis study divided the primary contributors of non-helmet use behavior into three levels for the SD model development. The SD model can be used to develop policies for mitigating helmet misuse, which in turn improves the safety performance of construction sites.

Objective: The goal of the present study was to determine the expression of yes-associated protein 1 (YAP1) in renal tissues of mice with lupus nephritis (LN) and elucidate its role in the progression of renal fibrosis. Methods: C57BL/6 mice and MRL/lpr mice were selected for experimental comparison. Mouse kidney tissues were removed and sectioned for hematoxylin and eosin staining, Masson’s trichome staining, Sirius staining, and immunohistochemistry. The mRNA and protein levels of YAP1 in mouse kidney tissues were detected, and the correlation between YAP1 and fibronectin (FN) mRNA levels was analyzed. Mouse renal epithelial cells were used for in vitro experiments. After transfection and stimulation, the cells were divided into 4 groups, namely the C57BL/6 serum group (group 1), the MRL/lpr serum group (group 2), the MRL/lpr serum + siRNA-negative control group (group 3), and the MRL/lpr serum + siRNA-YAP1 group (group 4). Epithelial-mesenchymal transition (EMT) markers in each group were detected by Western blotting and immunofluorescence staining. Serum creatinine, blood urea nitrogen, and urinary protein levels were detected and assessed for their correlation with YAP1 mRNA levels by Spearman’s analysis. Results: Compared to C57BL/6 mice, MRL/lpr mice exhibited obvious changes in fibrosis in renal tissues. In addition, YAP1 expression was significantly higher in the renal tissues of MRL/lpr mice than in those of C57BL/6 mice, and YAP1 mRNA levels were positively correlated with those of FN. YAP1 silencing in lupus serum-stimulated cells could effectively relieve serum-induced EMT. Finally, we observed that YAP1 mRNA levels in mouse kidney tissue were significantly and positively correlated with the degree of renal function injury. Conclusion: YAP1 expression in the kidney tissues of LN mice was higher than that observed in normal mice, indicating that YAP1 may play an important role in the occurrence and development of LN.

Background Heart failure (HF) is a serious and advanced stage of various cardiac diseases with high mortality and rehospitalization rates. Phosphoglycerate mutase 2 (PGAM2) overexpression was identified in the serum of patients with HF. Material/methods One hundred and fifty-three cases of HF were included in the present work. According to New York Heart Association (NYHA) classification, 22 were grade II, 84 were grade III, and 47 were grade IV. Serum PGAM2, NT-proBNP, B-type natriuretic peptide (BNP), troponin T (TNT), and Cys-C of HF patients were detected using ELISA assay. Left ventricular ejection fraction, left ventricular end-diastolic inner diameter, and left atrium (LA) inner diameter of the included cases were also detected by the cardiac color Doppler. Results The number of patients with atrial fibrillation was significantly higher in NYHA IV group than in groups II and III with statistical difference (p < 0.05). The serum PGAM2, NT-proBNP, and Cys-C were significantly higher in NYHA IV group than in NYHA II and NYHA III groups (p all < 0.05). NT-proBNP had the highest prediction efficacy of HF severity and PGAM2 was also a potential biomarker for HF severity evaluation with relatively high sensitivity, specificity, and area under the ROC. The overall survival among NYHA II, III, and IV groups were statistically different (p = 0.04) with the median survival time of 25 months for NYHA III and IV groups. Conclusion PGAM2 is a new promising biomarker for evaluation of the severity of HF. Combination detection using multiple serum factors such as PGAM2, NT-proBNP, BNP, TNT, and Cys-C can improve the HF severity differential diagnosis performance.

Tumor microenvironment is a complex ecosystem composed of tumor extracellular matrix, fibroblasts, blood vessels, and immune cells, promoting tumor development by secreting various growth factors, hydrolase, and inflammatory factors. Tumor-associated macrophages (TAMs) constitute the largest number of immune cells in the TME, and they have a "double-edged sword" effect on tumor growth, invasion, metastasis, angiogenesis, and immunosuppression. Under the regulation of different cytokines in the TME, the bidirectional TAMs can switch their phenotypes between tumoricidal M1-like and pro-tumorigenic M2-like macrophages. TAM polarization suggests that scientists can use this property to design drugs targeting this regulation as a promising immunotherapy strategy to enhance tumor therapy efficiency. In this review, we summarize a brief introduction of TAMs and their implications for tumorigenesis. Next, we review recent advances in designing various functionalized nanomedicines and their applications in nanomedicine-based cancer therapies that target TAMs by killing them, inhibiting macrophage recruitment, and repolarizing them from pro-tumorigenic M2-like to tumoricidal M1-like macrophages. Simultaneously, the regulation of nanomedicines on the signaling pathways accounting for these effects is also summarized. This review will not only provide background scientific information for the understanding of TAMs and their roles in cancer treatment but also help scientists design nanomedicines based on tumor TAMs, which can help achieve better clinical treatment outcomes for tumors.

Background Prostate cancer (PCa) is known to be suitable for hypofractionated radiotherapy due to the very low α/β ratio (about 1.5–3 Gy). However, several randomized controlled trials have not shown the superiority of hypofractionated radiotherapy over conventionally fractionated radiotherapy. Besides, in vivo and in vitro experimental results show that the linear-quadratic (LQ) model may not be appropriate for hypofractionated radiotherapy, and we guess it may be due to the influence of fractionation schedules on the α/β ratio. Therefore, this study attempted to estimate the α/β ratio in different fractionation schedules and evaluate the applicability of the LQ model in hypofractionated radiotherapy. Methods The maximum likelihood principle in mathematical statistics was used to fit the parameters: α and β values in the tumor control probability (TCP) formula derived from the LQ model. In addition, the fitting results were substituted into the original TCP formula to calculate 5-year biochemical relapse-free survival for further verification. Results Information necessary for fitting could be extracted from a total of 23,281 PCa patients. A total of 16,442 PCa patients were grouped according to fractionation schedules. We found that, for patients who received conventionally fractionated radiotherapy, moderately hypofractionated radiotherapy, and stereotactic body radiotherapy, the average α/β ratios were 1.78 Gy (95% CI 1.59–1.98), 3.46 Gy (95% CI 3.27–3.65), and 4.24 Gy (95% CI 4.10–4.39), respectively. Hence, the calculated α/β ratios for PCa tended to become higher when the dose per fraction increased. Among all PCa patients, 14,641 could be grouped according to the risks of PCa in patients receiving radiotherapy with different fractionation schedules. The results showed that as the risk increased, the k (natural logarithm of an effective target cell number) and α values decreased, indicating that the number of effective target cells decreased and the radioresistance increased. Conclusions The LQ model appeared to be inappropriate for high doses per fraction owing to α/β ratios tending to become higher when the dose per fraction increased. Therefore, to convert the conventionally fractionated radiation doses to equivalent high doses per fraction using the standard LQ model, a higher α/β ratio should be used for calculation.

Recently optical amplification technologies for mode-division multiplexing (MDM) transmission systems and networks have attracted great interest. In this article, we first propose a compact structure of few-mode Erbium-doped fiber amplifier (FM-EDFA) for weakly-coupled MDM amplification, which is characterized by weakly-coupled few-mode Erbium-doped fiber (EDF), cascaded mode-selective couplers (MSCs) for spatial mode control of pump lights, and few-mode wavelength multiplexer (FM-WMUX) for pump/signal coupling. Compared to previous studies, the proposed FM-EDFA has a similar structure with commercial single-mode EDFA (SM-EDFA) and can support weakly-coupled MDM transmission without inducing large modal crosstalk. Then related components are designed and fabricated for a 2-mode proposed FM-EDFA. The mode-field mismatching between transmission FMF and EDF under central alignment is investigated by simulation. Thanks to the effective suppression of modal crosstalk for the optical components, the transmission FMF, the EDF and their coupling, we experimentally demonstrate the first weakly-coupled MDM-WDM amplification and transmission over 15-km 2-mode FMF with 10-Gb/s optical on-off keying (OOK) modulation and direct detection. The proposed FM-EDFA can be extended to MDM transmission systems and networks supporting more modes.

In recent years, the issue of environmental pollution caused by the manufacturing industry has been widely criticized. To explore the relationship between capital enrichment and environmental pollution, the mediating effect model was constructed by using the panel data of 28 sub-sectors of China’s manufacturing industry from 2011 to 2017. Results show that the phenomenon of capital enrichment is mainly concentrated in industries with high-profit margins, intensive technology, national policy support, and resource or national monopolistic positions. Both capital enrichment and innovation capability have a promotion effect on inhibiting environmental pollution, but with the decline of innovation capability, the effect of capital enrichment on pollution weakens. Innovation capability plays a mediating role, which leads to the mechanism of capital enrichment ? innovation capability ? environmental pollution. The impact of capital enrichment on environmental pollution under different levels of innovation capability is heterogeneous, and the effect is stronger in high-tech industries.

Purpose We identified the risk predictors related to prostate cancer (PCa) metastasis using contemporary data in a community setting. Then, we assessed the performance of indications for bone imaging recommended from the NCCN, AUA and EAU guidelines. Methods Using the Surveillance, Epidemiology, and End Results database (2010–2015), we collected clinicopathological information from PCa patients. The associated risk factors found by multivariate analyses were used to establish forest plots and nomograms for distant metastasis (DM) and bone(s)-only metastasis (BM). We next evaluated the NCCN, AUA and EAU guidelines indications for the discovery of certain subgroups of patients who should receive bone imaging. Results A total of 120,136 patients were eligible for analysis, of which 96.7% had no metastasis. The odds ratios of positive DM and BM results were 13.90 times and 15.87 times higher in patients with a histologic grade group (GG) 5 than in the reference group. The concordance index of the nomograms based on race, age, T/N stage, PSA, GG, percentage of positive scores for predicting DM and BM was 0.942 and 0.928, respectively. Performance of the NCCN, AUA and EAU guidelines was high and relatively similar in terms of sensitivity (93.2–96.9%) and negative predictive value (99.8–99.9%). NCCN guidelines had the highest accuracy, specificity and positive likelihood ratio, while negative likelihood ratio was lowest in AUA guideline. Conclusion Histologic GG 5 was the foremost factor for DM and BM. NCCN-based recommendations may be more rational in clinical practice. Nomograms predicting metastasis demonstrate high accuracy.

Pegylated recombinant human granulocyte colony-stimulating factor (PEG-rhG-CSF, pegfilgrastim) is a long-acting derivative of recombinant human granulocyte colony-stimulating factor with limited renal clearance and a longer half-life. It is used for the prevention of febrile neutropenia, owing to its capacity to promote neutrophil recovery. In this study, the pharmacokinetics, pharmacodynamics, safety, and immunogenicity of 2 formulations of PEG-rhG-CSF were evaluated in healthy Chinese subjects. Twenty-four male subjects who received a single dose of subcutaneous PEG-rhG-CSF 100 µg/kg were randomized to either treatment A (3 mg/mL) or treatment B (1 mg/mL). Noncompartmental pharmacokinetic parameters of PEG-rhG-CSF were derived from serum concentration-time data. In addition, absolute neutrophil count (ANC) as a pharmacodynamic maker, immunogenicity through antidrug antibody testing, and safety were evaluated. The mean area under the concentration-time curve from time zero to the last quantifiable concentration (AUC0-t ) and the mean maximum concentration (Cmax ) of PEG-rhG-CSF after treatment A were 5070 ng·h/mL and 125 ng/mL, respectively; these values were comparable to those measured after treatment B (5340 ng·h/mL and 123 ng/mL, respectively). The mean value of area under the △ANC (baseline-adjusted ANC)-time curve and the maximum △ANC values were 4380 × 109 h/L and 33.1 × 109 /L, respectively, in the treatment A group, and 5170 × 109 h/L and 38.6 × 109 /L, respectively, in the treatment B group. The pharmacokinetic and pharmacodynamic profiles were similar for the 2 PEG-rhG-CSF formulations following a single dose of 100 µg/kg. The safety and immunogenicity profiles were also similar, with no significant differences. The dose adjustment of PEG-rhG-CSF was not considered necessary for formulation transformation.

Type 2 diabetes mellitus (T2DM) has become an expanding global public health problem. Although the glucocorticoid receptor (GR) is an important regulator of glucose metabolism, the relationship between circulating glucocorticoids (GCs) and the features of T2DM remains controversial. Here, we show that 17-hydroxyprogesterone (17-OHP), an intermediate steroid in the biosynthetic pathway that converts cholesterol to cortisol, binds to and stimulates the transcriptional activity of GR. Hepatic 17-OHP concentrations are increased in diabetic mice and patients due to aberrantly increased expression of Cyp17A1. Systemic administration of 17-OHP or overexpression of Cyp17A1 in the livers of lean mice promoted the pathogenesis of hyperglycemia and insulin resistance, whereas knockdown of Cyp17A1 abrogated metabolic disorders in obese mice. Therefore, our results identify a Cyp17A1/17-OHP/GR–dependent pathway in the liver that mediates obesity-induced hyperglycemia, suggesting that selectively targeting hepatic Cyp17A1 may provide a therapeutic avenue for treating T2DM.

Objective: Previous studies have reported an association between iron deficiency (ID) and increased thyroid peroxidase antibody (TPO-Ab) during early pregnancy. The objective of this study was to explore the relationship between ID and thyroid dysfunction, as well as thyroid autoantibodies, during the second trimester of pregnancy. Methods: A total of 1,592 pregnant women (13 to 28 weeks gestation) were enrolled in this cross-sectional study. According to serum ferritin (SF) concentrations, they were divided into ID (SF 4.0 mIU/L and free thyroxine [FT4] within the reference range) and thyroid autoimmunity. Results: The prevalence of ID was 23.43% (373/1,592). Compared with the non-ID group, the ID group had lower FT4 levels (13.94 pmol/L [8.91 to 29.82 pmol/L] versus 14.63 pmol/L [8.22 to 47.24 pmol/L]; P

Purpose This study aims to identify predictive local recurrence risk factors and site-specific local recurrence pattern of upper tract urothelial carcinoma (UTUC) with different primary tumor locations. Methods Three hundred and eighty-nine UTUC patients with radical nephroureterectomy were included in this study. Univariate and multivariate Cox proportional hazards regressions were performed to measure the risk of local recurrence. We also mapped the position of local recurrence sites stratified by primary tumor locations. Results A total of 73 patients (18.7%) developed local recurrence within a median follow-up of 41 months (range, 3-80 months). For patients with local recurrence, the median interval of local recurrence was 9 months. Ureter tumor, multifocality, T stage, G grade, lymph node metastasis (LNM), lymph node dissection (LND), and lymph vascular invasion (LVI) were all significantly associated with increased local recurrence by univariable analyses (P < 0.05). Only multifocality, T3–4, G3, and LNM remained independent predictors of increased local recurrence by multivariable analyses. Adjuvant radiotherapy could reduce the local recurrence (HR = 0.177; 95% CI 0.064-0.493, P = 0.001). Patients with local recurrence had poorer cancer-specific survival (4-year cancer-specific survival rate 36 ± 7.5% vs 88.4 ± 2.2%, P = 0.000). We evaluated local recurrence pattern stratified by tumor locations. Para-aortic lymph node region was the most common recurrence area for all the patients. Left-sided UTUC had more than 70% recurrent lymph nodes in the left para-aortic region (LPA). For right-sided UTUC patients, recurrent para-aortic lymph nodes distributed in the LPA (33.3%), aortocaval (AC) (41.5%), and right paracaval (RPC) (25.2%) regions. Recurrence in the internal and external iliac regions was only found in the distal ureter group (P < 0.05). Renal pelvic fossa recurrence was only found in renal pelvic tumor (22.2%, P = 0.007). The ureter tumor bed recurrence rate was higher for ureter patients (P = 0.001). Conclusions Multifocality, T3–4, G3, and LNM are predictors of higher local recurrence rate of UTUC. Adjuvant radiotherapy can reduce local recurrence rate. Local recurrence patterns are different according to primary tumor locations.

B lymphocytes are the source of autoantibodies against the thyroid-stimulating hormone receptor (TSHR) in Graves’ disease (GD). Characterization of autoimmune B-cell expression profiles might enable a better understanding of GD pathogenesis. To reveal this, the expression levels of long noncoding RNAs (lncRNAs) and mRNAs (genes) in purified B cells from patients with newly diagnosed GD and healthy individuals were compared using microarrays, which elucidated 604 differentially expressed lncRNAs (DE-lncRNAs) and 410 differentially expressed genes (DEGs). GO and pathway analyses revealed that the DEGs are mainly involved in immune response. A protein–protein interaction network presented experimentally validated interactions among the DEGs. Two independent algorithms were used to identify the DE-lncRNAs that regulate the DEGs. Functional annotation of the deregulated lncRNA–mRNA pairs identified 14 pairs with mRNAs involved in cell proliferation. The lncRNAs TCONS_00022357-XLOC_010919 and n335641 were predicted to regulate TCL1 family AKT coactivator A (TCL1A), and the lncRNA n337845 was predicted to regulate SH2 domain containing 1A (SH2D1A). TCL1A and SH2D1A are highly involved in B-cell proliferation. The differential expression of both genes was validated by qRT-PCR. In conclusion, lncRNA and mRNA expression profiles of B cells from patients with GD indicated that the lncRNA–mRNA pairs n335641–TCL1A, TCONS_00022357-XLOC_010919–TCL1A, and n337845–SH2D1A may participate in GD pathogenesis by modulating B-cell proliferation and survival. Therefore, the identified lncRNA and mRNA may represent novel biomarkers and therapeutic targets for GD.

Renalase is a novel enzyme that can regulate blood pressure by degrading circulating catecholamines. We aimed to evaluate the possible effect of rs2296545, rs2576178 and rs10887800 polymorphisms of the

Foreign body ingestion is common in the pediatric population. We report a case of ingestion of sunflower seeds that migrated in the left neck through a pyriform sinus fistula, ultrasound plays an important role in preoperative diagnosis and is a useful tool for diagnosing both pyriform sinus fistulas and radiolucent foreign bodies.

Influenza and pneumonia can be prevented by vaccination, but they remain major causes of morbidity and mortality in age‐related diseases. In most areas of China, the rates of influenza and pneumococcal vaccination are relatively low and public awareness of vaccination remains insufficient. Thus, it is essential to recommend influenza and Streptococcus pneumoniae vaccination to elderly people in clinical practice. Based on recently published studies and related documents issued by several vaccination authorities, such as the World Health Organization, the National Health and Wellness Committee, the Chinese Center for Disease Control and Prevention, the US Centers for Disease Control and Prevention, and the US Advisory Committee on Immunization Practices, we propose official recommendations for influenza and S pneumoniae vaccination in elderly people in China.

Purpose Our purpose was to compare toxicity and biochemical control in postprostatectomy patients treated with conventional (66 Gy) or dose-intensified (72 Gy) radiation therapy. Methods and Materials Patients who had stage pT3-4, positive surgical margins, or rising prostate-specific antigen ≥ 0.2 ng/mL after radical prostatectomy were randomly assigned to receive either 66 Gy in 33 fractions or 72 Gy in 36 fractions. A primary endpoint was to assess the difference in biochemical progression-free survival (bPFS) between these 2 cohorts, and secondary endpoints were to assess differences in genitourinary (GU), gastrointestinal (GI), and hematologic toxicities between these 2 cohorts. bPFS was estimated by the Kaplan–Meier method and toxicities were compared using the χ2 test. Results Between September 2011 and November 2016, 144 patients were enrolled: 71 patients to the 66 Gy cohort and 73 patients to the 72 Gy cohort. The median follow-up time was 48.5 months (range, 14-79 months). There was no difference in 4-year bPFS between the 66 Gy and 72 Gy cohorts (75.9% vs 82.6%; P = .299). However, in patients with a higher Gleason score (8-10), the 72 Gy cohort had statistically significant improvement in bPFS compared with the 66 Gy cohort (79.7% vs 55.7%; P = .049). Toxicity analysis showed no difference in ≥2 acute or late GI or GU toxicities between these 2 cohorts. A total of 48 patients were scored as urinary incontinence before radiation therapy, of which 39 (81.3%) reported incontinence recovery or stable at 1-year follow-up, and only 9 (18.8%) patients reported worsening. There was no difference between the 2 cohorts in urinary incontinence either at baseline or at 1-year follow-up. Conclusions Dose escalation (72 Gy) demonstrated no improvement in 4-year bPFS compared with the 66 Gy regimen. However, the dose escalation was not associated with greater acute or late GU or GI toxicities and did not increase urinary incontinence.

BackgroundNecrotizing enterocolitis (NEC) is the leading cause of death among preterm infants born at MethodsOur prospective multicenter, double-blinded, randomized, controlled trial will include infants born at n = 1549) will receive at least two feeds of fresh human milk (i.e., within 4 h of expression) per day from the time of enrollment until 32 weeks’ corrected age or discharge to home. Infants in the control group (n = 1549) will receive previously frozen human milk following the current standard protocols. Following informed consent, enrolled infants will be randomly allocated to the control or fresh human milk groups. The primary outcome is the composite outcome mortality or NEC ≥ stage 2 at 32 weeks’ corrected age, and the secondary outcomes are mortality, NEC ≥ stage 2, NEC needing surgery, late-onset sepsis, retinopathy of prematurity (ROP), bronchopulmonary dysplasia (BPD), weight gain, change in weight, increase in length, increase in head circumference, time to full enteral feeds, and finally, the number and type of critical incident reports, including feeding errors.DiscussionOur double-blinded, randomized, controlled trial aims to examine whether fresh human milk can improve infant outcomes. The results of this study will impact both Chinese and international medical practice and feeding policy for preterm infants. In addition, data from our study will inform changes in health policy in NICUs across China, such that mothers are encouraged to enter the NICU and express fresh milk for their infants.Trial registrationChinese Clinical Trial Registry; #ChiCTR1900020577; registered January 1, 2019;http://www.chictr.org.cn/showprojen.aspx?proj=34276

Particle-phase air pollution is a leading risk factor for premature death globally and impacts climate by scattering or absorbing radiation and changing cloud properties. Within the Beijing-Tianjin-Hebei region of China, where there are severe air quality problems, several municipalities have begun implementing a coal-to-electricity program that bans residential coal and provides subsidies for electricity and electric-powered heat pumps. We used GEOS-Chem to evaluate two complete residential coal-to-electricity transitions—a Beijing-off scenario and Beijing-Tianjin-Hebei-off scenario—each relative to a base case. We estimate that within China, the ambient fine particulate matter (PM2.5) reductions in the Beijing-off scenario could lead to 1,900 (95% CI: 1,200–2,700) premature deaths avoided annually, while the Beijing-Tianjin-Hebei-off scenario could lead to 13,700 (95% CI: 8,900–19,600) premature deaths avoided annually. Additionally, we estimate that the residential-coal-ban scenarios will result in a positive top-of-the-atmosphere aerosol direct radiative effect (DRE) (model domain average: Beijing-off: 0.023 W m–2; Beijing-Tianjin-Hebei-off: 0.30 W m–2) and a negligible cloud-albedo aerosol indirect effect (AIE) (Beijing-off: 0.0001 W m–2; Beijing-Tianjin-Hebei-off: 0.0027 W m–2). To evaluate the uncertainty of the radiative effects, we calculated the DRE under four black-carbon mixing-state assumptions and both the DRE and AIE assuming three different black-carbon-to-organic-aerosol (BC:OA) ratios for residential-coal emissions. Although the magnitude of our radiative forcing estimates varied across sensitivity cases, the domain average remained positive. When only considering the aerosol-related effects of the aforementioned coal-ban scenarios, we predict substantial health benefits, but do not anticipate a climate “co-benefit”, because removing aerosol emissions leads to a warming tendency. However, if the coal-to-electricity program results in less net greenhouse gas emissions due to the replacement heaters, the policy may be able to achieve health and climate “co-benefits”.

Commercially viable cultivars adapted to U.S. production regions that meet consumer acceptance criteria are desperately needed by the growing domestic edamame industry. Here, we report the development and release of 'VT Sweet' (Reg. no. CV-542, PI 699062), the first vegetable soybean [Glycine max (L.) Merr.] cultivar released by Virginia Tech. VT Sweet is a late maturity group (MG) V cultivar (relative maturity 5.6, 129 d to harvest) with determinate growth habit, purple flowers, gray pubescence, tan pod wall, and yellow hila. VT Sweet has superior characteristics for edamame such as large pod size (13.9 g/10 pods; 40.4 mm long, 11.4 mm wide, and 7.6 mm thick) and low one-bean pod proportion (15%), as well as low pod pubescence density (359 hairs/2.4 cm(2)). VT Sweet also showed high overall consumer acceptability (6.0 +/- 1.7; 9 = like extremely) and favorable tolerance to native pests. When compared with the commercial edamame check 'UA Kirksey', VT Sweet showed 102% of the check yield, a higher average field emergence rate (74.9 vs. 68.1%), and comparable consumer acceptability (6.05 vs. 6.10). Therefore, VT Sweet is an ideal cultivar for growers who are interested in commercial edamame production in the mid-Atlantic region of the United States. USDA-NIFAUnited States Department of Agriculture (USDA) [2018-51181-28384, 237 436 1016465] Published version We thank USDA-NIFA for the financial support (Grant No. 2018-51181-28384; Accession No. 237 436 1016465) that led to the development of VT Sweet. The authors also thank Sam Chang, Lila Chung, Raymond Chung, and Shannon Ellis for their advice and Muliang Peng, Lin Barrack, Tom Pridgen, Michelle Lee, XingboWu, William Singer, and Joseph Oakes for their technical support in cultivar development. Public domain – authored by a U.S. government employee

Nonalcoholic fatty liver disease (NAFLD) represents a spectrum of chronic liver disease ranging from simple steatosis (NAFL) to nonalcoholic steatohepatitis (NASH). However, the molecular mechanisms of NASH progression remain incompletely understood. White adipose tissue (WAT) has emerged as an important endocrine organ and contributes not only to the initial stage of NAFLD, but also to its severity. In the current study, through transcriptomic analysis we identified increased expression of Sparcl1, a secreted glycoprotein, in the WAT from NASH mice. Plasma Sparcl1 levels were similarly elevated and positively correlated with hepatic pathological features in NASH patients. Functional studies showed that both chronic injection of recombinant Sparcl1 protein and overexpression of Sparcl1 exaggerated hepatic inflammation and liver injury in mice. In contrast, genetic ablation of Sparcl1, knockdown of Sparcl1 in WAT, and treatment with a Sparcl1-neutralizing antibody dramatically alleviated diet-induced NASH pathogenesis. Mechanistically, Sparcl1 promoted the expression of C-C motif chemokine ligand 2 (CCL2) in hepatocytes through binding to Toll-like receptor 4 (TLR4) and activation of the NF-κB/p65 signaling pathway. Genetically or pharmacologically blocking the CCL2/CCR2 pathway attenuated the hepatic inflammatory response evoked by Sparcl1. Thus, our results demonstrated an important role for Sparcl1 in NASH progression, suggesting a potential target for therapeutic intervention.

The field-orthogonal temporal modes (TM) of electromagnetic fields form a new framework for quantum information. A lot of efforts have been made to develop the tools for photonic quantum information processing in TM framework. However, the distribution of temporally multiplexed quantum states over long distance optical fibers has not been realized yet. As a first step toward long distance distribution of TMs, we study fourth-order interference and show how the dispersion influence the field spectrum by launching a pulsed field in different temporal modes into a M-Z interferometer with unbalanced dispersion induced by transmission fibers in two arms. The investigation is useful for further investigating the distribution of temporally multiplexed quantum states in fiber network.

We discuss three emerging applications of wavelength conversion: 1) hybrid amplification outside of EDFA band, based on a combination of two wavelength converters and an EDFA, 2) spatial-mode-selective wavelength conversion, and 3) generation of spatial-mode-entangled photon pairs.

Immune checkpoint inhibitors (ICIs) have changed the landscape of cancer treatment and are emerging as promising curative treatments in different type of cancers. However, only a small proportion of patients have benefited from ICIs and there is an urgent need to find robust biomarkers for individualized immunotherapy and to explore the causes of immunotherapy resistance. In this article, we review the roles of immune cells in the tumor microenvironment (TME) and discuss the effects of ICIs on these cell populations. We discuss the potential of the functional interaction between the TME and cancer cells as a predictive biomarker for ICIs. Furthermore, we outline the potential personalized strategies to improve the effectiveness of ICIs with precision.

The aim is to comprehensively and accurately assess potential relationships between single nucleotide polymorphisms (SNP) and lung cancer (LC) risk by summarizing the evidence in systematic reviews and meta-analyses. This umbrella review was registered with the PROSPERO international prospective register of systematic reviews under registration number CRD42020204685. The PubMed, Web of Science, and Embase databases were searched to identify eligible systematic reviews and meta-analyses from inception to August 14, 2020. The evaluation of cumulative evidence was conducted for associations with nominally statistical significance based on the Venice criteria and false positive report probability (FPRP). This umbrella review finally included 120 articles of a total of 190 SNP. The median number of studies and sample size included in the meta-analyses were five (range, 3–52) and 4 389 (range, 354–256 490), respectively. A total of 85 SNP (in 218 genetic models) were nominally statistically associated with LC risk. Based on the Venice criteria and FPRP, 13 SNP (in 22 genetic models), 47 SNP (in 99 genetic models), and 55 SNP (in 94 genetic models) had strong, moderate, and weak cumulative evidence of associations with LC risk, respectively. In conclusion, this umbrella review indicated that only 13 SNP (of 11 genes and one miRNA) were strongly correlated to LC risk. These findings can serve as a general and helpful reference for further genetic studies.

PurposeWe retrospectively analyzed the oncological outcomes of T3 or G3 distal ureteral urothelial carcinoma (DUUC) underwent partial ureterectomy (PU) followed by adjuvant radiotherapy (ART).MethodsFrom January 2008 to September 2019, clinical data from a total of 221 patients with pathologic T3 or G3 who underwent PU or RNU at our hospital were analyzed. 17 patients of them were treated with PU+ART, 72 with PU alone and 132 with radical nephroureterectomy (RNU). Clinicopathologic outcomes were evaluated. Survival was assessed using the Kaplan-Meier method. Cox regression addressed recurrence-free survival (RFS), metastasis-free survival (MFS), cancer specific survival (CSS) and overall survival (OS).ResultsMedian age and follow-up time were 68 (IQR 62-76) years old and 43 (IQR 28-67) months, respectively. In univariate and multivariable analyses, no lymph node metastasis(LNM) and ART were independent prognostic factors of RFS (p=0.031 and 0.016, respectively). ART significantly improved 5-year RFS compared with the PU alone, (67.6% vs. 39.5%, HR: 2.431, 95%CI 1.210-4.883, p=0.039). There was no statistical difference in 5-year RFS between PU+ART and RNU groups (67.6% vs. 64.4%, HR=1.113, 95%CI 0.457-2.712, p=0.821). Compared with PU alone or RNU, PU+ART demonstrated no statistical difference in 5-year MFS (PU+ART 73.2%, PU 57.2%, RNU69.4%), CSS (70.7%, 55.1%, 76.6%, respectively), and OS (70.7%, 54.1%, 69.2%, respectively).ConclusionsFor distal ureteral urothelial carcinoma patients with T3 or G3, adjuvant radiotherapy could significantly improve recurrence-free survival compared with partial ureterectomy alone. There was no significant difference between survival outcomes of PU+ART and radical nephroureterectomy.

Prader–Willi syndrome (PWS) is a complex genetic syndrome caused by the loss of function of genes in 15q11-q13 that are subject to regulation by genomic imprinting and expressed from the paternal allele only. The main clinical features of PWS patients are hypotonia during the neonatal and infantile stages, accompanied by delayed neuropsychomotor development, hyperphagia, obesity, hypogonadism, short stature, small hands and feet, mental disabilities, and behavioral problems. However, PWS has a clinical overlap with other disorders, especially those with other gene variations or chromosomal imbalances but sharing part of the similar clinical manifestations with PWS, which are sometimes referred to as Prader–Willi syndrome-like (PWS-like) disorders. Furthermore, it is worth mentioning that significant obesity as a consequence of hyperphagia in PWS usually develops between the ages of 1 and 6 years, which makes early diagnosis difficult. Thus, PWS is often not clinically recognized in infants and, on the other hand, may be wrongly suspected in obese and intellectually disabled patients. Therefore, an accurate investigation is necessary to differentiate classical PWS from PWS-like phenotypes, which is imperative for further treatment. For PWS, it is usually sporadic, and very rare family history and affected siblings have been described. Here, we report the clinical and molecular findings in a three-generation family with a novel 550-kb microdeletion affecting the chromosome 15 imprinting center (IC). Overall, the present study finds that the symptoms of our patient are somewhat different from those of typical PWS cases diagnosed and given treatment in our hospital. The familial occurrence and clinical features were challenging to our diagnostic strategy. The microdeletion included a region within the complex small nuclear ribonucleoprotein polypeptide protein N (SNRPN) gene locus encompassing the PWS IC and was identified by using a variety of techniques. Haplotype studies suggest that the IC microdeletion was vertically transmitted from an unaffected paternal grandmother to an unaffected father and then caused PWS in two sibling grandchildren when the IC microdeletion was inherited paternally. Based on the results of our study, preimplantation genetic diagnosis (PGD) was applied successfully to exclude imprinting deficiency in preimplantation embryos before transfer into the mother’s uterus. Our study may be especially instructive regarding accurate diagnosis, differential diagnosis, genetic counseling, and PGD for familial PWS patients.

The rapid growth of cloud computing in cloud datacenters in recent decades greatly increases the brown energy consumption in datacenters, and hence significant increase of carbon emission that negatively impacts on the environment as well as the monetary cost. More and more cloud service providers are adopting renewable energy as the energy supply to offset the consumption of brown energy. Meanwhile, an increasing number of renewable energy generators have been built to meet the needs. However, the instability of the renewable energy cannot guarantee the support to the datacenter and the energy competition of different datacenters may lead to datacenter energy outage. In this paper, we focus on the problem of how to match different renewable energy generators to the datacenters from different cloud providers to minimize the carbon emission, monetary cost, and service level objective (SLO) violation due to renewable energy shortage. The challenges here are that the datacenters may compete in energy requesting, the renewable energy generation is not stable and the decision should be made quickly. There have been no previous efforts devoting to this problem. To solve the problem, we first test several machine learning techniques on long-term prediction accuracy on renewable energy generation and energy demand using real traces and identify SARIMA for the prediction. We then propose a multi-agent reinforcement learning based method (MARL) for each datacenter to determine how much renewable energy to request from each generator based on the predicted results. We also propose a deadline guaranteed job postponement method (DGJP) to postpone executing unurgent jobs upon insufficient renewable energy supply. The trace-driven experiments show that MARL outperforms other methods by increasing up to 35% SLO satisfaction ratio, and reducing up to 19% (0.33 billion dollars in 90 days) total monetary cost and 33% total carbon emission, and DGJP further improves the performance.

Key Points Question What are the care practices and outcomes for very preterm infants in Chinese neonatal intensive care units? Findings In this cohort study of 9552 very preterm infants from 57 tertiary neonatal intensive care units throughout China in 2019, 86% received complete care, among whom 95% survived and 57% survived without major morbidities. Only 76% of the infants received antenatal corticosteroids, and 12% of the infants received delivery room continuous positive airway pressure. Meaning The findings of this study suggest that survival and survival without major morbidity of very preterm infants in Chinese neonatal intensive care units remain lower than in high-income countries and clinical quality improvement as well as systems and health services reorganization are needed to improve outcomes., Importance The Chinese Neonatal Network was established in 2018 and maintains a standardized national clinical database of very preterm or very low-birth-weight infants in tertiary neonatal intensive care units (NICUs) throughout China. National-level data on outcomes and care practices of very preterm infants (VPIs) in China are lacking. Objective To assess the care practices in NICUs and outcomes among VPIs in China. Design, Setting, and Participants A cohort study was conducted comprising 57 tertiary hospitals from 25 provinces throughout China. All infants with gestational age (GA) less than 32 weeks who were admitted to the 57 NICUs between January 1 and December 31, 2019, were included. Main Outcomes and Measures Care practices, morbidities, and survival were the primary outcomes of the study. Major morbidities included bronchopulmonary dysplasia, severe intraventricular hemorrhage (grade ≥3) and/or periventricular leukomalacia, necrotizing enterocolitis (stage ≥2), sepsis, and severe retinopathy of prematurity (stage ≥3). Results A total of 9552 VPIs were included, with mean (SD) GA of 29.5 (1.7) weeks and mean (SD) birth weight of 1321 (321) g; 5404 infants (56.6%) were male. Antenatal corticosteroids were used in 75.6% (6505 of 8601) of VPIs, and 54.8% (5211 of 9503)were born through cesarean delivery. In the delivery room, 12.1% of VPIs received continuous positive airway pressure and 26.7% (2378 or 8923) were intubated. Surfactant was prescribed for 52.7% of the infants, and postnatal dexamethasone was prescribed to 9.5% (636 of 6675) of the infants. A total of 85.5% (8171) of the infants received complete care, and 14.5% (1381) were discharged against medical advice. The incidences of the major morbidities were bronchopulmonary dysplasia, 29.2% (2379 of 8148); severe intraventricular hemorrhage and/or periventricular leukomalacia, 10.4% (745 of 7189); necrotizing enterocolitis, 4.9% (403 of 8171 ); sepsis, 9.4% (764 of 8171); and severe retinopathy of prematurity, 4.3% (296 of 6851) among infants who received complete care. Among VPIs with complete care, 95.4% (7792 of 8171) survived: 65.6% (155 of 236) at 25 weeks’ or less GA, 89.0% (880 of 988) at 26 to 27 weeks’ GA, 94.9% (2635 of 2755)at 28 to 29 weeks’ GA, and 98.3% (4122 of 4192) at 30 to 31 weeks’ GA. Only 57.2% (4677 of 8171) of infants survived without major morbidity: 10.5% (25 of 236) at 25 weeks’ or less GA, 26.8% (48 of 179) at 26 to 27 weeks’ GA, 51.1% (1409 of 2755) at 28 to 29 weeks’ GA, and 69.3% (2904 of 4192) at 30 to 31 weeks’ GA. Among all infants admitted, the survival rate was 87.6% (8370 of 9552)and survival without major morbidities was 51.8% (4947 of 9552). Conclusions and Relevance The findings of this study suggest that survival and survival without major morbidity of VPIs in Chinese NICUs have improved but remain lower than in high-income countries. Comprehensive and targeted quality improvement efforts are needed to provide complete care for all VPIs, optimize obstetrical and neonatal care practices, and improve outcomes., This cohort study evaluates the care practices used for as well as the survival and major morbidities among very preterm infants hospitalized in neonatal intensive care units in China.

Many epidemiological studies have confirmed thatICAM-1gene single-nucleotide polymorphisms (SNPs) are associated with susceptibility of various cancers, but there are relatively few studies on the relationship betweenICAM-1gene polymorphisms and the risk of cervical cancer. Therefore, we aimed to explore the potential role ofICAM-1gene polymorphisms and the combined effect of SNPs in the pathogenesis of cervical cancer in Han women in northern China. This case–control group includes 488 cases of cervical cancer, 684 cases of cervical precancerous lesions, and 510 healthy females. Multiplex polymerase chain reaction (PCR) combined with the next-generation sequencing method was used for the determination of gene polymorphisms (rs5498, rs3093030, and rs281432). In our study, we divide cervical cancer into two subgroups: cervical squamous cell carcinoma (CSCC) group and cervical adenocarcinoma (CAC) group. We analyzed the alleles and genotypes of all research subjects using multivariate logistic regression analysis combined with 10,000 permutation tests. In addition, we also analyzed the distribution of haplotypes of the three SNPs in cervical cancer and cervical precancerous lesions. We found that the T allele and the dominant model of rs3093030 were associated with the susceptibility of cervical cancer (p= 0.042,p= 0.040, respectively). However, the significance disappeared after the Bonferroni correction for multiple testing (p> 0.05). For rs5498, its mutant gene G, the codominant model, and the dominant model could reduce the risk of CAC (p= 0.009,p= 0.028,p= 0.011, respectively). Significant differences remained after Bonferroni correction (p< 0.05, all). In addition, the frequency of haplotype “CTG” was significantly lower in the CAC group than in the controls. In conclusion, the study suggested thatICAM-1gene polymorphisms may have a potential role in the pathogenesis of cervical cancer in the northern Chinese Han population.

Metformin is the first-line therapy for the treatment of type 2 diabetes (T2D) through mechanism of reduction in hepatic glucose production and fasting plasma glucose. Dorzagliatin is a novel glucokinase activator (GKA) that improves glucose and insulin sensitivity which significantly reduces post meal plasma glucose. Combination of dorzagliatin with metformin would offer benefits through the synergy of two mechanisms. In this randomized, double-blind, placebo-controlled phase 3 trial (NCT03141073), the efficacy and safety of dorzagliatin add-on to metformin in T2D patients were assessed. Eligible T2D patients (n=767) were randomly assigned in a 1:1 ratio to dorzagliatin group or placebo group add-on to metformin (1500 mg/day) for a 24-week double-blind treatment, then followed by a 28-week open-label treatment with dorzagliatin in all patients. The primary efficacy endpoint was the change from baseline in the glycated hemoglobin(HbA1c) level at week 24 and the safety was assessed throughout the trial. At week 24, the HbA1c was reduced from baseline in dorzagliatin group, superior to placebo (-1.02% vs. -0.36%; ETD, -0.66%; 95% CI, -0.79 to -0.53; P

Improvement of glucose and insulin sensitivity remains an unmet medical need in diabetes management, in which the underlying cause of type 2 diabetes(T2D) was not well addressed by current treatment. We report the findings of a randomized, double-blind, placebo-controlled, phase 3 clinical trial (NCT03173391) to evaluate the efficacy and safety of dorzagliatin, a dual-acting glucokinase (GK) allosteric modulator, which enhances the GK activity in T2D patients in a glucose dependent manner, and has demonstrated its effects in blood glucose control through improvement of glucose sensitivity in T2D patients. Eligible drug-naïve T2D patients (n=463) were randomly assigned to dorzagliatin group or placebo group in a 2:1 ratio for a 24-week double-blind treatment, then followed by a 28-week open-label treatment with dorzagliatin in all patients. The primary efficacy endpoint was the change from baseline in the glycated hemoglobin (HbA1c) level at week 24. Safety was assessed throughout the trial. At week 24, the change from baseline in HbA1c was -1.07% in the dorzagliatin group and -0.50% with placebo (ETD, -0.57%; 95%CI, -0.79 to -0.36; P

Yuan Xu,1– 4 Huan Yang,2,5 Jing Wang,6 Xiaoying Li,2,5 Chengjun Xue,6 Changchun Niu,2 Pu Liao1,2 1Chongqing Medical University, Chongqing, 400014, People’s Republic of China; 2Department of Clinical Laboratory, Chongqing General Hospital, University of Chinese Academy of Sciences, Chongqing, 400014, People’s Republic of China; 3Chongqing College, University of Chinese Academy of Sciences, Chongqing, 400014, People’s Republic of China; 4Department of Clinical Laboratory, Affiliated Hospital of North Sichuan Medical College, Nanchong, 637000, People’s Republic of China; 5Southwest Medical University, Luzhou, 646000, People’s Republic of China; 6Department of Clinical Laboratory, Chongqing Public Health Medical Center, Chongqing, 400036, People’s Republic of ChinaCorrespondence: Pu Liao Email liaopu@ucas.ac.cnBackground: COVID-19 infections are still at pandemic levels globally and there are currently no specific drugs to treat these infections. Previous studies have demonstrated that serum albumin levels were abnormally low in COVID-19 patients and might be used as a prognosis biomarker. Supplemental albumin has been used as an experimental therapeutic method. However, dynamic evaluation of albumin in patients with COVID-19 was limited and whether serum albumin could predict the prognosis of these patients is unknown.Methods: We enrolled 79 COVID-19 patients in the present study and reviewed electronic medical laboratory records. Data was processed using SPSS software (Version 20.0) and correlation analysis was performed between serum albumin and other clinical and laboratory findings.Results: Serum albumin levels were gradually decreased both in severe and non-severe COVID-19 patients. Moreover, 17.7% of the patients presented with hypoalbuminemia at least one time during 3 consecutive weekly time points. The hypoalbuminemia group displayed more severe disease and comorbidity that included fever, fatigue, headache, and dizziness on admission. Moreover, serum albumin levels were positively correlated with lymphocyte and RBC numbers, Hb and prealbumin levels as well as with total T cell numbers and the presence of CD4+ and CD8+ T cells. In contrast, there was a negative correlation with C-reactive protein levels and this was an indicator of patient recovery.Conclusion: Our results demonstrated that hypoalbuminemia was common in COVID-19 patients and its levels were linked to disease severity. Patients with fever, fatigue and headache or dizziness on admission were more likely to experience hypoalbuminemia. Dynamic monitoring of serum albumin is therefore necessary and should be performed during COVID-19 patient treatments as a tool for evaluating the prognosis of COVID-19 infections.Keywords: COVID-19, SARS-CoV-2, albumin, liver function, prognosis

Objective To provide national-level antibiotic use data from Chinese neonatal intensive care units to inform future antimicrobial stewardship using a large contemporary cohort of preterm infants in China. Study design This retrospective cohort study enrolled all infants less than 340/7 weeks of gestation admitted to 25 tertiary neonatal intensive care units across China between May 1, 2015, and April 30, 2018. The antibiotic use rate (AUR) was defined as the number of days an infant was prescribed with 1 or more antibiotics divided by the total length of hospital stay. Results Among 24 597 eligible infants, 21 736 (88.4%) infants received antibiotics. The median AUR was 441 per 1000 patient-days (IQR, 242-692 per 1000 patient-days). The median duration of each antibiotic course was 9 days (IQR, 6-14 days). Overall, 64.6% infants received broad-spectrum antibiotics, with a median broad-spectrum AUR of 250 per 1000 patient-days (IQR, 0-500 per 1000 patient-days), accounting for 70.7% of all antibiotic use days. Overall, 68.7% of all antibiotic use occurred among infants without infection-related morbidities, with a median duration of 8 days (IQR, 6-13 days) for each course. Only 22.9% episodes of culture-negative sepsis were prescribed with antibiotics for 7 or fewer days, and 34.7% were treated with antibiotics for more than 14 days. For early antibiotic use, the median duration of antibiotic therapy within 7 days after birth was 7 days (IQR, 4-7 days). Conclusions A high AUR among infants without infections, prolonged antibiotic durations, and excessive use of broad-spectrum antibiotics were the main problems of antibiotic use in Chinese neonatal intensive care units and should be high-impact focuses for future stewardship interventions.

Background Our objective was to study the phenotype of and molecular genetic mechanisms underlying congenital protein C (PC) deficiency in Chinese neonates. We report the case of a neonate who presented 4 h after birth with purpura fulminans of the skin and thrombosis in the kidney. We also carried out a through literature review to study the genotype and phenotype, relevance, diagnosis, management, and prognosis of neonates with congenital PC deficiency in China. Case presentation and literature review Following a septic work-up and check of PC and protein S (PS) levels that showed PC deficiency, we investigated the patient’s and her parents’ genotypes. Our patient was found to have a plasma PC level of 0.8%. Molecular testing revealed a compound heterozygous mutation of the PROC gene: From the father, a c._262 G > T p. ASP88Tyr mutation in exon 4; from the mother, a C. 400 + 5G mutation in intron 5 that had been previously reported as likely pathogenic. Both parents were found to have heterozygous mutations for PC deficiency. In China, 5 other cases of congenital PC deficiency in the neonatal period were reported in the literature. In those cases, purpura fulminans and thrombosis were the main symptoms, and homozygous or compound heterozygous mutations of the PROC gene were identified. Conclusion Congenital PC deficiency should be ruled out for neonates presenting with purpura fulminans and thrombosis.