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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.

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.

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.

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.

Background and aims Nonalcoholic fatty liver disease (NAFLD) is characterized by accumulation of excessive triglycerides (TGs) in hepatocytes. Obesity is a major risk factor for developing fatty liver, although the intracellular molecular basis remains largely unclear. N6 -methyladenosine (m6 A) RNA methylation is the most common internal modification in eukaryotic mRNA. Approach and results In the present study, by m6 A sequencing and RNA sequencing, we found that both m6 A enrichment and mRNA expression of lipogenic genes were significantly increased in leptin-receptor-deficient db/db mice. Importantly, our results showed that YT521-B homology domain-containing 2 (Ythdc2), an m6 A reader, was markedly down-regulated in livers of obese mice and NAFLD patients. Suppression of Ythdc2 in livers of lean mice led to TG accumulation, whereas ectopic overexpression of Ythdc2 in livers of obese mice improved liver steatosis and insulin resistance. Mechanistically, we found that Ythdc2 could bind to mRNA of lipogenic genes, including sterol regulatory element-binding protein 1c, fatty acid synthase, stearoyl-CoA desaturase 1, and acetyl-CoA carboxylase 1, to decrease their mRNA stability and inhibit gene expression. Conclusions Our findings describe an important role of the m6 A reader, Ythdc2, for regulation of hepatic lipogenesis and TG homeostasis, which might provide a potential target for treating obesity-related NAFLD.

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.

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.

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

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.

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.

Prognostic significance of heart rate (HR) in heart failure with preserved ejection fraction (HFpEF) remains poorly understood. To evaluate the association of HR and beta-blocker use with all-cause mortality and the optimal HR range in patients with HFpEF and sinus rhythm (SR). During a follow-up of 2.7 years (IQR 1.2–4.1 years), the 330 patients with median age 73 (IQR 64–79) years, 52.1% men, were included. HFpEF was defined as patients with EF ≥ 50%. The outcome measure was all-cause mortality. In total, 96 (29.1%) of patients with HFpEF and SR died. A linear tendency between HR and mortality was observed in SR. Compared to the reference strata HR ≤ 60 bpm, HR increment was associated with progressively increased risk in mortality (Chi-square = 13.90, Log rank P = 0.001) by Kaplan–Meier analyses. Univariate Cox regression showed that in SR, compared with that in HR 61–80 bpm, the unadjusted hazard ratios for mortality were 0.41 (95% CI 0.23–0.74, P = 0.003) in HR ≤ 60 bpm, 1.38 (95% CI 0.85–2.24, P = 0.189) in HR > 80 bpm. Multivariate Cox regression showed that compared with that in HR 61–80 bpm, the adjusted hazard ratios for mortality were 0.37 (95% CI 0.19–0.75, P = 0.005) in HR ≤ 60 bpm, 0.96 (95% CI 0.52–1.74, P = 0.899) in HR > 80 bpm. Univariate Cox regression showed that the unadjusted hazard ratios for mortality were 0.52 (95% CI 0.33–0.84, P = 0.003) in patients with beta-blocker as compared patients without beta-blocker. Multivariate Cox regression showed that the adjusted hazard ratios for mortality were 0.48 (95% CI 0.26–0.87, P = 0.016) in patients with beta-blocker as compared patients without beta-blocker. HR is independently associated with increased all-cause mortality in SR and a lower HR (≤ 60 bpm) is favorable for better outcome in HFpEF patients with SR. Beta-blocker use is associated with reduced mortality and a lower HR is associated with reduced mortality in HFpEF patients with SR.

Background Berberine (BBR), a natural compound extracted from Chinese herb, has been shown to effectively attenuate nonalcoholic fatty liver disease (NAFLD) in clinic. However, the mechanism underlying the effect of BBR is not fully understood. Stearyl-coenzyme A desaturase 1 (SCD1) mediates lipid metabolism in liver. Therefore, we hypothesized that SCD1 mediated the beneficial effect of BBR on NAFLD. Methods The expression of SCD1 was measured in the liver of NAFLD patients and ob/ob mice. The effect of BBR on NAFLD was evaluated in C57BL/6 J mice on high fat diet (HFD). The effect of BBR was also investigated in HepG2 and AML12 cells exposed to high glucose and palmitic acid. Oil red O staining was performed to detect triglyceride (TG) level. Quantitative real-time polymerase chain reaction and Western blot were used to detect the messenger ribonucleic acid (mRNA) and protein expression of target genes. The activity of SCD1 promoter was measured by dual-luciferase reporter assay. Results The expression of SCD1 was increased in the liver of NAFLD patients and ob/ob mice. BBR reduced hepatic TG accumulation and decreased the expressions of hepatic SCD1 and other TG synthesis related genes both in vivo and in vitro. Knockdown of SCD1 expression mimicked the effect of BBR decreasing TG level in steatotic hepatocytes, whereas overexpression of SCD1 attenuated the effect of BBR. Mechanistically, BBR promoted the phosphorylation of AMP-activated protein kinase (AMPK) and sterol regulatory element-binding protein-1c (SREBP-1c) in HepG2 cells and the liver of HFD-fed mice. Activation of the AMPK-SREBP-1c pathway and sterol regulatory element (SRE) motif in SCD1 promoter (-920/-550) was responsible for the BBR-induced suppression of SCD1. Conclusion BBR reduces liver TG synthesis and attenuates hepatic steatosis through the activation of AMPK-SREBP-1c-SCD1 pathway.

Background This study aimed to examine the performance of the four risk of malignancy index (RMI) in discriminating borderline ovarian tumors (BOTs) and benign ovarian masses in daily clinical practice. Methods A total of 162 women with BOTs and 379 women with benign ovarian tumors diagnosed at the Second Affiliated Hospital of Harbin Medical University from January 2012 to December 2016 were enrolled in this retrospective study. Also, we classified these patients into serous borderline ovarian tumor (SBOT) and mucinous borderline ovarian tumor (MBOT) subgroup. Preoperative ultrasound findings, cancer antigen 125 (CA125) and menopausal status were reviewed. The area under the curve (AUC) of receiver operator characteristic curves (ROC) and performance indices of RMI I, RMI II, RMI III and RMI IV were calculated and compared for discrimination between benign ovarian tumors and BOTs. Results RMI I had the highest AUC (0.825, 95% CI: 0.790–0.856) among the four RMIs in BOTs group. Similar results were found in SBOT (0.839, 95% CI: 0.804–0.871) and MBOT (0.791, 95% CI: 0.749–0.829) subgroups. RMI I had the highest specificity among the BOTs group (87.6, 95% CI: 83.9–90.7%), SBOT (87.6, 95% CI: 83.9–90.7%) and MBOT group (87.6, 95% CI: 83.9–90.7%). RMI II scored the highest overall in terms of sensitivity among the BOTs group (69.75, 95% CI: 62.1–76.7%), SBOT (74.34, 95% CI: 65.3–82.1%) and MBOT (59.18, 95% CI: 44.2–73.0%) group. Conclusion Compared to other RMIs, RMI I was the best-performed method for differentiation of BOTs from benign ovarian tumors. At the same time, RMI I also performed best in the discrimination SBOT from benign ovarian tumors.

Aims/Introduction Diabetes prevalence in China has increased, but the trend in gestational diabetes mellitus prevalence is unclear. The objective of the present study was to examine the prevalence of gestational diabetes in Xiamen, China, and its association with maternal risk factors. Materials and Methods This linked‐database cohort study used the Medical Birth Registry of Xiamen. Between 1 March 2011 and 30 March 2018, 78,572 women who were diagnosed with gestational diabetes mellitus (GDM) were enrolled in the study. Maternal factors associated with the prevalence of GDM were examined using multivariate logistic regression. Results A total of 13,738 (17.6%) pregnant women were diagnosed with GDM according to the International Association of Diabetes and Pregnancy Study Groups criteria. GDM prevalence ranged from 15.5% (2012) to 19.9% (2017). Increasing age was associated with GDM; women aged >40 years versus those aged >25 years had an adjusted odds ratio (OR) of 5.91 (95% confidence interval [CI] 4.202–8.314). A positive correlation was observed between weight and GDM risk; obese women versus normal‐weight women had an adjusted OR of 2.508 (95% CI 2.253–2.792). Family history of diabetes and hypertension were more commonly observed among women with GDM. Multivariate analysis showed that family history of diabetes (OR 1.101, 90% CI 1.028–1.180), weight gain during early pregnancy (OR 1.087, 90% CI 1.052–1.124) and systolic blood pressure (OR 1.015, 90% CI 1.011–1.020) were risk factors associated with GDM incidence. Conclusions GDM affects 17.6% of all pregnant women in Xiamen. Age and maternal obesity were major contributors to GDM. The trend of GDM risk remained stable during the study.

Pharynx-larynx cancer is a complex malignant tumor with the sixth-highest morbidity and mortality rate worldwide. The telomerase reverse transcriptase TERT-CLPTM1L gene, located on chromosome 5p15.33, plays a key role in the occurrence and progression of various cancer. The purpose of this hospital-based case-control study of patients in northern China was to explore the association between two single-nucleotide polymorphisms (SNPs) rs401681 in TERT and rs2736100 in CLPTM1L and the risk of head and neck cancer. We collected samples and relative characteristics and then analyzed the relationship between SNPs and pharynx-larynx cancer susceptibility by logistic regression analysis. The results suggested that the male patients carrying CT and CT+CC genotype model of rs401681 was associated with reduced risk of pharynx-larynx cancer compared with the CC genotype (adjusted odds ratios were 0.701 and 0.704, and 95% confidence intervals were 0.495-0.992 and 0.506-0.980; p-values were 0.045 and 0.038, respectively). In addition, we found that subjects with allele-C showed a relatively low risk of pharyngeal cancer when smoking exposure history was obtained. But the limitation is that in the future we need to further investigate about the exact functional effect of these two variant genes and a larger scale sample. Overall, in this research, our results show that the TERT-CLPTM1L gene could be a meaningful biomarker for pharynx-larynx cancer susceptibility.

Aim: We studied the association between two single-nucleotide polymorphisms (SNPs: rs4787050 and rs8045980) in RBFOX1 and lung cancer risk, and explored the interaction between the two SNPs and exposure to cooking oil fume on lung cancer risk in northeast Chinese female nonsmokers. Methods: Northeast Chinese female nonsmokers were enrolled into the study (people with lung cancer, 647; people without lung cancer, 675). All statistical analyses were performed using SPSS software. Results: The SNPs rs4787050 and rs8045980 showed a significant association with susceptibility to lung cancer. Moreover, cooking oil fume exposure was found to increase the risk of lung cancer. However, no gene–environment interactions were discovered. Conclusion: The present study revealed that rs4787050 and rs8045980 in RBFOX1 may be meaningful as a novel biomarker for lung cancer susceptibility.

Cryptosporidium is one of the most important parasitic protozoa that can be transmitted through food and water contamination. With the increasing report of Cryptosporidium infections in wild birds, especially in herbivorous waterfowl, concerns have been raised for oocyst contamination of water and food supplies, which in turn can cause human and domestic animal infections in areas neighboring wild birds' habitats. This review discusses the epidemiology, species, and genotypes distribution of Cryptosporidium in wild birds around the world. The overall prevalence of Cryptosporidium in wild birds was calculated as 3.96% (1945/49129), with 6 Cryptosporidium species (C. andersoni, C. parvum, C. meleagridis, C. avium, C. baileyi, and C. galli) and 5 genotypes (Goose genotype I, Goose genotype II, Avian genotype I, Avian genotype III, and Avian genotype VI) reported. As wild birds mainly live in the wild, control method for the Cryptosporidium infection in wild birds is still lacking, which increases the probability of disease transmission from wild birds to humans. The main purpose of this review is to highlight the Cryptosporidium infection in wild birds and its transmission, associated risk factors, and their prevention, illustrating the necessity of multidisciplinary approaches toward screening and control of Cryptosporidium infections.

Background To find new diagnostic markers for idiopathic membranous nephropathy (IMN) and also conduct preliminary explorations into the possible pathogenesis of IMN by comparing the expression of microRNA‐451a (miR‐451a), miR‐106a, miR‐19b, miR‐17, and phosphatase and tensin homolog (PTEN) protein in the serum of patients with IMN and healthy controls. Methods The expression levels of miR‐451a, miR‐106a, miR‐19b, and miR‐17 in the serum of patients in the IMN group (n = 55, age: 50.2 ± 12.1 years) and the control group (n = 58, age 47.4 ± 13.1 years) were measured by quantitative real‐time polymerase chain reaction (qRT‐PCR), and the concentration of serum PTEN protein was determined by enzyme‐linked immunosorbent assay (ELISA). Results Compared with the control group, the expression of miR‐106a, miR‐19b, and miR‐17 was decreased significantly in the IMN group, whereas PTEN protein concentration was increased significantly in the IMN group. The areas under the receiver operating characteristic curve (AUC) of serum miR‐106a, miR‐19b, miR‐17, and PTEN were 0.66 (95% confidence interval [CI], 0.56–0.76), 0.81 (95% CI, 0.73–0.89), 0.69 (95% CI, 0.59–0.79), and 0.86 (95% CI, 0.79–0.93), respectively. The level of serum PTEN protein was negatively correlated with the expression of miR‐106a and miR‐19b. PTEN concentration was positively correlated with serum urea (Urea), creatinine (Crea), cystatin C (Cysc), 24 h urine total protein (24 h‐UP) and negatively correlated with albumin (Alb) and estimated glomerular filtration rate (eGFR). Conclusions MiR‐106a, miR‐19b, miR‐17, and PTEN are involved in the pathogenesis of IMN and may become new biomarkers for the diagnosis of IMN., The concentration of serum PTEN protein was significantly increased in IMN as compared with controls. Compared with miR‐106a, miR‐19b, and miR‐17, the diagnostic performance of PTEN was the highest in IMN. Serum PTEN was positively correlated with Urea, Crea, Cysc, and 24h‐UP, and negatively correlated with Alb and eGFR. Serum PTEN was involved in the pathogenesis of IMN, and may become a new biomarker for the diagnosis of IMN.

Most gastric cancer and gastroesophageal junction carcinoma (GEJ) patients are already in the advanced stage at the time of diagnosis. Thus, the probability of radical gastrectomy is low, and surgical treatment alone has a poor prognosis due to the high recurrence rate. In order to reduce the recurrence and distant metastasis after surgery, there have been many attempts made to improve the perioperative treatment of advanced localized gastric cancer, but no uniform criteria exist. Over recent years, immunotherapy has revolutionized cancer treatment, and immune checkpoint inhibitors (ICIs) have shown excellent efficacy across various types of tumors, becoming a potential treatment after surgery, chemotherapy, radiotherapy, and targeted therapy. However, the efficacy of single-agent ICIs for gastric cancer is still unsatisfactory. As comprehensive, chemotherapy-based treatment has become the standard care for locally advanced gastric cancer, exploring combination treatment with immune checkpoint inhibitors (ICIs) may be valuable to improving survival outcomes. Here, we report a 66-year-old male with dysphagia diagnosed with GEJ and was defined as clinical stage (cT4N2M0) and Siewert type II, characterized as mismatch repair proficient (pMMR) and programmed cell death ligand-1 (PD-L1) negative; surprisingly, with anti-PD-1 antibody plus SOX (S-1: a combination of tegafur, gimeracil, and oteracil+ oxaliplatin) as perioperative therapy, the patient achieved pathological complete remission (pCR), which indicates that the addition of ICIs to chemotherapy as a perioperative comprehensive treatment might provide a promising strategy option for GEJ. In addition, we review the current status of perioperative comprehensive treatment, in hope that this may provide some reference value for clinical decision-making.

PurposeThe aim of this retrospective study was to probe into clinicopathological features and prognosis of early-onset gastric cancer (EOGC) patients aged ≤ 45 years old.MethodsThis study selected 154 young gastric cancer patients aged ≤ 45 years old and 158 elderly gastric cancer patients aged > 50 years old admitted to West China Hospital of Sichuan University in 2009-2019 as the research object. These patients were further divided into two groups according to whether tumor can be resected radically. The following parameters were analyzed: age, gender, helicobacter pylori (HP) infection status, Her-2 status, pathological type and stage, chemotherapy, tumor differentiation degree, overall survival (OS).ResultsMore than 3,000 patients with gastric carcinoma were screened, and 154 young gastric cancer patients aged ≤ 45 years old were identified as EOGC. Among them, the number of female patients in EOGC group was significantly higher than that of males, accounting for 63.6%. In addition, EOGC were associated with diffuse Laur´en type and poorly differentiated tumors. Interestingly, the Kaplan–Meier method showed that the OS of unresectable EOGC group was significantly lower than that of unresectable LOGC group (P = 0.0005) and chemotherapy containing paclitaxel tended to be more effective in the young people (P = 0.0511). Nevertheless, there was no significant difference in OS between young and elderly patients with gastric cancer in the radical resection group (P = 0.3881).ConclusionEOGC patients have a worse prognosis than late-onset gastric cancer (LOGC) patients with advanced unresectable gastric cancer. Palliative surgery or chemotherapy containing paclitaxel may improve the OS of unresectable young individuals with gastric cancer. Additional randomized controlled trials are required for guiding clinical practice.

Background With the extended life expectancy of the Chinese population and improvements in surgery and anesthesia techniques, the number of aged patients undergoing surgery has been increasing annually. However, safety, effectiveness, and quality of life of aged patients undergoing surgery are facing major challenges. In order to standardize the perioperative assessment and procedures, we have developed a perioperative evaluation and auxiliary decision-making system named “Aged Patient Perioperative Longitudinal Evaluation–Multidisciplinary Trial (APPLE-MDT)”. Methods We will conduct a perioperative risk evaluation and targeted intervention, with follow-ups at 1, 3, and 6 months after surgery. The primary objective of the study is to evaluate the effectiveness of the “Aged Patient Perioperative Longitudinal Evaluation-Multiple Disciplinary Trial Path” (hereinafter referred to as the APPLE-MDT path) in surgical decision-making for aged patients (≥75 years) undergoing elective surgery under non-local anesthesia in the operating room. The secondary objectives of the study are to evaluate the postoperative outcome and health economics of the APPLE-MDT path applied to the surgical decision-making of aged patients (≥75 years) undergoing elective surgery under non-local anesthesia and to optimize intervention strategies for aged patients undergoing surgery to reduce the occurrence of postoperative complications and improve the quality of life after surgery. Discussion It is necessary to formulate a reliable, effective, and concise evaluation tool, which can effectively predict the perioperative complications and mortality of aged patients, support targeted intervention strategies, and allow for a more comprehensive risk and benefit analysis, thereby forming an effective senile perioperative surgery management path. It is expected that the implementation of this protocol can reduce the occurrence of postoperative complications, improve the postoperative quality of life, shorten hospital stay, reduce hospitalization expenses, reduce social burden, and allow the elderly to have a good quality of life after surgery. Trial registration ChiCTR, ChiCTR1800020363, Registered 15 December 2018.

Objective: To describe cardiovascular pharmacological support in infants born at Design: A secondary analysis of data from a multicenter randomized controlled study (REIN-EPIQ). A questionnaire regarding cardiovascular support practices was also completed by all participating NICUs.Setting: Twenty-five tertiary hospitals from 19 provinces in China.Patients: All infants born at Measures and Main Results: Among the 26,212 preterm infants 3 days. Prolonged cardiovascular pharmacological support (>3 days) was independently associated with lower rates of survival without morbidity in very-low-birth-weight infants, compared with infants with shorter durations. Dopamine was the most commonly used cardiovascular agent. The cardiovascular pharmacological support rates varied from 1.9 to 65.8% among the participating NICUs.Conclusions: The rate of cardiovascular pharmacological support within the first postnatal week was high with prolonged durations in Chinese NICUs. Marked variation in cardiovascular support existed among participating NICUs. Cardiovascular pharmacological support during the early postnatal period, especially prolonged, may be associated with adverse neonatal outcomes.Clinical Trial Registration: The original trial was registered as “Reduction of Infection in Neonatal Intensive Care Units using the Evidence-based Practice for Improving Quality” (ID: NCT02600195) on clinicaltrials.gov. https://clinicaltrials.gov/ct2/show/NCT02600195?term=NCT02600195&draw=2&rank=1.

Based on the principle of user-centered design, the elderly user needs analysis is an indispensable part of the assistive product design. For this purpose, we designed a questionnaire on assistive products for the elderly and carried out an investigation in China. The questionnaire was aimed at over 60 years of the elder at home. Through the analysis of the questionnaire answers, we tried to understand the physiological function characteristics of the elderly, as well as the assistive product needs, usage intention, usage status, user experience, etc. of the elderly and proposed the application strategies in the design of the assistive products for elderly.

IntroductionTo investigate the risk factors for the death in patients with COVID-19 with type 2 diabetes mellitus (T2DM).Research design and methodsWe retrospectively enrolled inpatients with COVID-19 from Wuhan Jinyintan Hospital (Wuhan, China) between December 25, 2019, and March 3, 2020. The epidemiological and clinical data were compared between non-T2DM and T2DM or between survivors and non-survivors. Univariable and multivariable Cox regression analyses were used to explore the effect of T2DM and complications on in-hospital death.ResultsA total of 1105 inpatients with COVID-19, 967 subjects with without T2DM (n=522 male, 54.0%) and 138 subjects with pre-existing T2DM (n=82 male, 59.4%) were included for baseline characteristics analyses. The complications were also markedly increased in patients with pre-existing T2DM, including acute respiratory distress syndrome (ARDS) (48.6% vs 32.3%, pConclusionsCoagulopathy was a major extrapulmonary risk factor for death in inpatients with COVID-19 with T2DM rather than ACI and AKI, which were well associated with mortality in inpatients with COVID-19 without T2DM.

Susceptibility of patients with chronic obstructive pulmonary disease (COPD) to cardiovascular autonomic dysfunction associated with exposure to metals in ambient fine particles (PM2.5, particulate matter with aerodynamic diameter ≤2.5 µm) remains poorly evidenced. Based on the COPDB (COPD in Beijing) panel study, we aimed to compare the associations of heart rate (HR, an indicator of cardiovascular autonomic function) and exposure to metals in PM2.5 between 53 patients with COPD and 82 healthy controls by using linear mixed-effects models. In all participants, the HR levels were significantly associated with interquartile range increases in the average concentrations of Cr, Zn, and Pb, but the strength of the associations differed by exposure time (from 1.4% for an average 9 days (d) Cr exposure to 3.5% for an average 9 d Zn exposure). HR was positively associated with the average concentrations of PM2.5 and certain metals only in patients with COPD. Associations between HR and exposure to PM2.5, K, Cr, Mn, Ni, Cu, Zn, As, and Se in patients with COPD significantly differed from those in health controls. Furthermore, association between HR and Cr exposure was robust in COPD patients. In conclusion, our findings indicate that COPD could exacerbate difference in HR following exposure to metals in PM2.5.

Background & aim Although serum fibroblast growth factor 21 (FGF21) levels are associated with liver fat content in non-alcoholic liver fat disease (NAFLD), the precise nature of the association remains undetermined. Therefore, this study aimed to explore the potential dose–response relationship between FGF21 and liver fat content in NAFLD. Methods For this exploratory study from a randomized trial, 220 NAFLD patients with central obesity were recruited via community-based screening and randomly assigned to either control, moderate or vigorous-moderate exercise groups for 12 months. After this exercise intervention, patients were followed-up for a further 12 months. Serum FGF21 levels were measured by ELISA. Intrahepatic triglyceride (IHTG) content was determined by proton magnetic resonance spectroscopy. Results Of the 220 patients, 149 (67.7%) were female; mean age was 53.9 ± 7.1 years and mean BMI was 28.0 ± 2.9 kg/m2 for all patients. Baseline IHGT increased gradually (P = 0.029 for trend) according to baseline serum FGF21 quartiles 1, 2, 3 and 4 (212.3, 358.9, 538.7 and 793.5 pg/mL, respectively). On grouping the distribution of serum FGF21 level changes into quartiles at month 12, the relative IHTG loss increased as serum FGF21 levels were reduced (P = 0.004 for trend). A similar trend was observed at month 24 (P = 0.006 for trend). Multivariate linear regression analysis revealed that changes in serum FGF21 levels were independently associated with changes in IHTG at both month 12 [β (SE), 0.136 (0.118); P = 0.048] and month 24 [β (SE), 0.152 (0.139); P = 0.041]. Using restricted cubic spline regression, changes in serum FGF21 were strongly and positively associated with their corresponding relative IHTG loss at both month 12 and follow-up (Poverall = 0.017, Pnon-linear = 0.044 and Poverall = 0.020, Pnon-linear = 0.361, respectively, for dose–response). Conclusion Serum FGF21 is strongly associated with liver fat content in a dose–response manner in centrally obese NAFLD patients. These findings support the use of serum FGF21 as a biomarker of liver fat content in NAFLD.

Long non‐coding RNAs (lncRNAs) are well known as crucial regulators to breast cancer development and are implicated in controlling autophagy. LncRNAs are also emerging as valuable prognostic factors for breast cancer patients. It is critical to identify autophagy‐related lncRNAs with prognostic value in breast cancer. In this study, we identified autophagy‐related lncRNAs in breast cancer by constructing a co‐expression network of autophagy‐related mRNAs‐lncRNAs from The Cancer Genome Atlas (TCGA). We evaluated the prognostic value of these autophagy‐related lncRNAs by univariate and multivariate Cox proportional hazards analyses and eventually obtained a prognostic risk model consisting of 11 autophagy‐related lncRNAs (U62317.4, LINC01016, LINC02166, C6orf99, LINC00992, BAIAP2‐DT, AC245297.3, AC090912.1, Z68871.1, LINC00578 and LINC01871). The risk model was further validated as a novel independent prognostic factor for breast cancer patients based on the calculated risk score by Kaplan‐Meier analysis, univariate and multivariate Cox regression analyses and time‐dependent receiver operating characteristic (ROC) curve analysis. Moreover, based on the risk model, the low‐risk and high‐risk groups displayed different autophagy and oncogenic statues by principal component analysis (PCA) and Gene Set Enrichment Analysis (GSEA) functional annotation. Taken together, these findings suggested that the risk model of the 11 autophagy‐related lncRNAs has significant prognostic value for breast cancer and might be autophagy‐related therapeutic targets in clinical practice.

Patients with type 2 diabetes mellitus (T2DM) are at risk of developing atherosclerotic cardiovascular disease (ASCVD) and chronic kidney disease (CKD), which are important causes of disabling and death in patients with T2DM. For the prevention and management of ASCVD or CKD, cardiovascular risk factors should be systematically evaluated, and ASCVD and CKD should be screened in patients with T2DM. In this consensus, we recommended that metformin should be used as the first-line therapy for patients with T2DM and ASCVD or very high cardiovascular risk, heart failure (HF) or CKD, and should be retained in the treatment regimen unless contraindicated or not tolerated. In patients with T2DM and established ASCVD or very high cardiovascular risk, addition of a glucagon-like peptide 1 receptor agonist (GLP-1RA) or sodium-glucose cotransporter type 2 (SGLT2) inhibitor with proven cardiovascular benefits should be considered independent of individualised glycated haemoglobin (HbA1C ) targets. In patients with T2DM and HF, an SGLT2 inhibitor should be preferably added regardless of HbA1C levels. In patients with T2DM and CKD, SGLT2 inhibitors should be preferred for the combination therapy independent of individualised HbA1C targets, and GLP-1RAs with proven renal benefits would be alternative if SGLT2 inhibitors are contraindicated. Moreover, the prevention of hypoglycaemia and management of multiple risk factors by comprehensive regimen, including lifestyle intervention, antihypertensive therapies, lipid-lowering treatment and antiplatelet therapies, should be kept in mind in treating patients with T2DM and ASCVD, HF or CKD.

Background Long noncoding RNAs (lncRNAs) are emerging as crucial contributors to the development of breast cancer and are involved in the stemness regulation of breast cancer stem cells (BCSCs). LncRNAs are closely associated with the prognosis of breast cancer patients. It is critical to identify BCSC-related lncRNAs with prognostic value in breast cancer. Methods A co-expression network of BCSC-related mRNAs-lncRNAs from The Cancer Genome Atlas (TCGA) was constructed. Univariate and multivariate Cox proportional hazards analyses were used to identify a stemness risk model with prognostic value. Kaplan–Meier analysis, univariate and multivariate Cox regression analyses and receiver operating characteristic (ROC) curve analysis were performed to validate the risk model. Principal component analysis (PCA) and Gene Set Enrichment Analysis (GSEA) functional annotation were conducted to analyze the risk model. Results In this study, BCSC-related lncRNAs in breast cancer were identified. We evaluated the prognostic value of these BCSC-related lncRNAs and eventually obtained a prognostic risk model consisting of 12 BCSC-related lncRNAs (Z68871.1, LINC00578, AC097639.1, AP003119.3, AP001207.3, LINC00668, AL122010.1, AC245297.3, LINC01871, AP000851.2, AC022509.2 and SEMA3B-AS1). The risk model was further verified as a novel independent prognostic factor for breast cancer patients based on the calculated risk score. Moreover, based on the risk model, the low- risk and high-risk groups displayed different stemness statuses. Conclusions These findings suggested that the 12 BCSC-related lncRNA signature might be a promising prognostic factor for breast cancer and can promote the management of BCSC-related therapy in clinical practice.

Through transcriptomic and epigenomic analysis, Wu et al. identify a glucocorticoid/Gadd45β/TET1-dependent pathway promoting PGC-1α gene transcription and, thereby, triggering gluconeogenesis, hepatic glucose production, and hyperglycemia., Although widely used for their potent anti-inflammatory and immunosuppressive properties, the prescription of glucocorticoid analogues (e.g., dexamethasone) has been associated with deleterious glucose metabolism, compromising their long-term therapeutic use. However, the molecular mechanism remains poorly understood. In the present study, through transcriptomic and epigenomic analysis of two mouse models, we identified a growth arrest and DNA damage-inducible β (Gadd45β)–dependent pathway that stimulates hepatic glucose production (HGP). Functional studies showed that overexpression of Gadd45β in vivo or in cultured hepatocytes activates gluconeogenesis and increases HGP. In contrast, liver-specific Gadd45β-knockout mice were resistant to high-fat diet– or steroid-induced hyperglycemia. Of pathophysiological significance, hepatic Gadd45β expression is up-regulated in several mouse models of obesity and diabetic patients. Mechanistically, Gadd45β promotes DNA demethylation of PGC-1α promoter in conjunction with TET1, thereby stimulating PGC-1α expression to promote gluconeogenesis and hyperglycemia. Collectively, these findings unveil an epigenomic signature involving Gadd45β/TET1/DNA demethylation in hepatic glucose metabolism, enabling the identification of pathogenic factors in diabetes., Graphical Abstract

Background A member of the S100 family of Ca2+-binding proteins, S100A1 is highly expressed in cardiac muscle tissue. Although this protein is considered an indicator of acute myocardial infarction (AMI), high-throughput and sensitive detection methods are still urgently needed. We constructed a rapid and sensitive method for detecting S100A1 and to investigate the clinical utility of S100A1 as a biomarker for the early diagnosis of AMI and subsequent prognostic assessments. We developed an automated chemiluminescent immunoassay to detect S100A1. We then analyzed the performance of the newly developed assay including evaluation of the analytical sensitivity, analytical selectivity, linear range, accuracy and repeatability. Methods We recruited 87 patients with AMI or angina pectoris to explore the value of this marker for the early diagnosis and prognostic assessment. Results The chemiluminescent-immune-based S100A1 assay had functional analytical sensitivity with a detection limit of 0.13 ng/ml, and a wide linear range of 0.13–31.66 ng/ml. It also exhibited good repeatability with intra-assay and inter-assay findings of 1.02 ng/ml) was notably associated with the poor prognosis of AMI patients after first PCI. Conclusions Measurement of circulating S100A1 concentrations with our newly developed chemiluminescent-immune-based assay shows potential for use in the clinic. This assay could enable early identification and prognostic assessment of AMI.

Problem: Interleukin-17A (IL-17A) has a role in sustaining normal pregnancy. IL-17A is also associated with thyroid autoimmunity during pregnancy. This study sought to investigate whether IL-17A is a risk factor for thyroid dysfunction during pregnancy in women negative for thyroid autoantibodies.Methods of Study: The study comprised 216 pregnant women with negative thyroid peroxidase antibody (TPOAb) and thyroglobulin antibody (TGAb) during the second trimester who provided blood samples for serum IL-17A, thyroid autoantibodies and thyroid function tests. To further evaluate the ratio of CD4+IL-17A+ Th17 cells, we collected peripheral blood from 26 women with thyroid-stimulating hormone (TSH) levels ≤ 2.5 mIU/L and 26 pregnancy-week matched women with TSH levels >2.5 mIU/L, along with samples from 20 women with TSH levels ≤ 4 mIU/L and 20 pregnancy-week matched women with TSH levels >4 mIU/L.Results: The serum IL-17A levels and ratios of CD4+IL-17A+ cells were significantly lower in women with TSH > 2.5 mIU/L than in those with TSH ≤ 2.5 mIU/L (both P < 0.01). Similar lower differences were noted in women with TSH > 4 mIU/L than in those with TSH ≤ 4 mIU/L (both P < 0.01). Moreover, serum TSH correlated negatively with IL-17A levels (β = −0.195, P = 0.004), but positively with the week of gestation (β = 0.284, P < 0.001). Logistic regression indicated that a lower serum IL-17A level was a risk factor for TSH > 2.5 mIU/L [OR = 0.453 (0.298–0.689), P = 0.000] and TSH > 4.0 mIU/L [OR = 0.588 (0.385–0.899), P = 0.013].Conclusion: A low serum IL-17A level during the second trimester is associated with an increased risk of TSH > 2.5 mIU/L and subclinical hypothyroidism.