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A growing number of environmental professionals are realizing that equitable and meaningful engagement of local community members in the development of programming is essential for catalyzing the durable, long-term action needed to conserve wildlife. Many who attempt to codesign programs with (not for) communities find that choosing the most effective strategies to accomplish this task is crucial and can oftentimes feel daunting. In this paper, a validated psychometric instrument called the Five Factors of Sustained Engagement (Five Factors) was used to analyze community engagement projects from two AZA-accredited institutions, highlighting how the leaders of each project believe they have fostered each factor in their projects. Professionals can use the Five Factors as guideposts and evaluation criteria to increase the long-term motivation of community members to engage in conservation efforts over time. The discussion offers strategies that psychological research has shown to increase long-term motivation for wildlife conservation and suggest how to implement them in the codesign of conservation programming with the communities that are impacted by it the most. Together, this synthesis offers an innovative, psychology-based approach to fostering and evaluating the success of sustainable community engagement for conservation Wildlife conservation projects are rarely su long-term engagement from the humans who are most impacted by those projects.

To investigate the efficacy and safety of bendamustine combined with gemcitabine, vinorelbine，glucocorticoids (BeGEV)±X regimen in treatment of patients with relapsed/refractory non-Hodgkin lymphoma.A total of 18 relapsed/ refractory non-Hodgkin lymphoma patients at the age of 18 years or older hospitalized in the First People's Hospital of Changzhou from March 2020 to March 2021 were selected. They received two or more cycles of BeGEV±X regimen. X could be anti-CD20 monoclonal antibody, PD-1-blocking antibodies, lenalidomide, BTK inhibitor, Bcl-2 inhibitor and so on according to patients' disease feature. The clinical efficacy and adverse effects were observed.In total, 18 patients completed two or more cycles of BeGEV±X regimen, including 14 with diffuse large B-cell lymphoma, one with low-grade follicular lymphoma, one with follicular lymphoma grade 3b, one with angioimmunoblastic T-cell lymphoma and one with peripheral T-cell lymphoma, not otherwise specified. 11 patients were male. The median age of the patients was 64 years old. 17 patients had modified Ann Arbor stage Ⅲ/Ⅳ disease. 13 patients had high- intermediate risk or high risk IPI score, while 15 patients had high-intermediate high risk or high risk NCCN-IPI score. 14 cases had extranodal sites of disease. And 6 cases had bulky disease. 12 patients experienced refractory disease, while 8 patients had received 3 line or more prior treatment. After two or three cycles of chemotherapy, the complete response rate was 6/18, the partial response rate was 3/18, and the objective response rate was 9/18. From the beginning of salvage chemotherapy to the end of follow-up, the median progression-free survival time was 130 days, and the median overall survival was 152 days. The most common grade 3 to 4 adverse events were hematologic toxicities, infection and febrile neutropenia.BeGEV±X is an effective salvage regimen in treatment of patients with relapsed/refractory non-Hodgkin lymphoma, while adverse events such as hematologic toxicities and infection should be closely monitored.苯达莫司汀联合方案治疗复发难治性非霍奇金淋巴瘤患者的疗效分析.探讨苯达莫司汀联合吉西他滨、长春瑞滨、激素（BeGEV）±X方案治疗复发难治性非霍奇金淋巴瘤患者的疗效及安全性.选取2020年3月至2021年3月常州市第一人民医院收治的18例年龄≥18岁复发难治性非霍奇金淋巴瘤患者，予BeGEV±X方案化疗，X根据患者疾病特征选用CD20单抗、PD-1抑制剂、来那度胺、BTK抑制剂、Bcl-2抑制剂等，观察临床疗效及毒副反应.共18例患者完成≥2疗程BeGEV±X方案化疗，其中弥漫大B细胞淋巴瘤14例，低级别滤泡性淋巴瘤患者1例，滤泡性淋巴瘤3b级患者1例，血管免疫母细胞性T细胞淋巴瘤1例，外周T细胞性淋巴瘤-非特指型1例。18例患者的中位年龄为64岁，11例男性，改良Ann Arbor分期Ⅲ/Ⅳ期为17例，IPI评分高中危及高危组13例，NCCN-IPI评分高中危及高危组15例，14例患者存在结外病变，6例患者存在大包块。12例患者为难治性淋巴瘤，8例患者既往经过3线及以上的治疗。2-3个疗程后进行疗效评估，完全缓解（CR）率为6/18，部分缓解（PR）率为3/18，总体缓解率（ORR）为9/18。从BeGEV挽救性化疗开始至随访截止，中位疾病无进展生存（PFS）时间为130 d，中位总生存（OS）时间为152 d。最常见的3/4级不良反应为血液学毒性、感染、中性粒细胞减少伴发热.苯达莫司汀联合吉西他滨、长春瑞滨、激素±X治疗复发难治性非霍奇金淋巴瘤具较好的疗效，治疗后需严密观察血液学毒性及感染等副反应.

Type-2 diabetes mellitus (T2DM) is a medical condition in which oral medications avail to patients to curb their hyperglycaemia after failed dietary therapy. However, individual responses to the prescribed pharmacotherapy may differ due to their clinical profiles, comorbidities, lifestyles and medical adherence. One approach is to identify similar patients within the same community to predict their likely response to the prescribed diabetes medications. This study aims to present an evidence-based diabetes medication recommendation system (DMRS) underpinned by patient similarity analytics. The DMRS was developed using 10-year electronic health records of 54,933 adult patients with T2DM from six primary care clinics in Singapore. Multiple clinical variables including patient demographics, comorbidities, laboratory test results, existing medications, and trajectory patterns of haemoglobin A1c (HbA1c) were used to identify similar patients. The DMRS was evaluated on four groups of patients with comorbidities such as hyperlipidaemia (HLD) and hypertension (HTN). Recommendations were assessed using hit ratio which represents the percentage of patients with at least one recommended sets of medication matches exactly the diabetes prescriptions in both the type and dosage. Recall, precision, and mean reciprocal ranking of the recommendation against the diabetes prescriptions in the EHR records were also computed. Evaluation against the EHR prescriptions revealed that the DMRS recommendations can achieve hit ratio of 81% for diabetes patients with no comorbidity, 84% for those with HLD, 78% for those with HTN, and 75% for those with both HLD and HTN. By considering patients’ clinical profiles and their trajectory patterns of HbA1c, the DMRS can provide an individualized recommendation that resembles the actual prescribed medication and dosage. Such a system is useful as a shared decision-making tool to assist clinicians in selecting the appropriate medications for patients with T2DM.

Objectives The present study investigated immune disorders and CCR7 expression in primary immune thrombocytopenia (ITP) patients and analyzed their changes and clinical significance before and after treatments. Methods Flow cytometry was used to detect the proportion of different immune cell subsets in the peripheral blood of 42 patients with ITP and 20 normal controls at different time points. Treatments included first-line drugs, such as glucocorticoids and intravenous immunoglobulin, and second-line therapy, such as interleukin-11 and Thrombopoietin receptor agonists (TPO-RA). Results An elevated CD4/CD8 ratio and a decreased NK cells and CD4+CD25+CD127 low regulatory T cells (Tregs) were found in pretreatment ITP patients compared to healthy controls. The newly diagnosed group had a higher CD4/CD8 ratio and more NK cells than in the relapsed group. Tregs of the remission group were higher than those of the recurrence group. The CD4+CCR7+, CD8+CCR7+, CCR7+ subset of B cells and NK cells showed higher increases in the newly diagnosed and the relapsed group compared to controls and remission group.CD4+CCR7+ and CD8+CCR7+ subset in the relapsed group were slightly higher than the newly diagnosed. The CCR7+ subsets of CD4+ T cells, CD8+ T cells, NK cells and B cells were lower in the remission group compared to the relapsed group. Higher level of the CD8+CCR7+ subset and lower NK cells were found in the remission group compared to the controls. The ratio between the CD4+CCR7+ subset and CD8+CCR7+ subset was lower in the ITP patients than in normal controls. There was a negative correlation between the CD8+CCR7+ subset and platelet count in the ITP patients. Conclusion ITP patients with CCR7 had immune disorders and high heterogeneity, and CCR7 was found to be involved in the pathogenesis of ITP. Further studies are needed to investigate the effective treatment for ITP by targeted regulation of CCR7.

Background Telemedicine helps to provide the safe management of stroke patients in the emergency department (ED) and has been used worldwide. However, we had limited experience of telestroke in Taiwan. We aimed to identify the quality of telestroke and compare it with the original face-to-face consultation model. Methods Among 178 consecutive acute ischemic stroke patients treated with intravenous tissue plasminogen activator (IVtPA) from January 1, 2018, to December 31, 2019, we compared two different consultation methods: face-to-face consultation and telestroke consultation. We collected data on demographics, the National Institutes of Health Stroke Scale (NIHSS) scores, Modified Rankin Scale (mRS) scores, time measurements (onset-to-arrival time, onset-to-telestroke activation time, and time of IVtPA administration (Door-to-Needle; DTN)). Results The mean age to receive a telestroke consultation was 66.6 years, 36% were female, and the median NIHSS score was 9. The median time from patient arrival to telestroke consult activation was 40 min, and the median DTN time was 11 min longer than for face-to-face consults (62 min versus 51 min, p = .01). Telestroke consultation, similar to a face-to-face consultation, resulted in safe IVtPA eligibility assessments and administration with post-thrombolysis ICH in 4% overall (4% telestroke, 3% face-to-face consultation; p = .851). The 90-day outcomes were not different for mRS score, dichotomized 0–2 (60% telestroke 59% face-to-face consultation; p = .961), or for mortality (16% telestroke, 9% face-to-face consultation; p = .292). Conclusion In the ED, consultation via the telestroke program provides equal quality to the original face-to-face consultation model to manage ischemic stroke.

This study looked at novel data sources for cardiovascular risk prediction including detailed lifestyle questionnaire and continuous blood pressure monitoring, using ensemble machine learning algorithms (MLAs). The reference conventional risk score compared against was the Framingham Risk Score (FRS). The outcome variables were low or high risk based on calcium score 0 or calcium score 100 and above. Ensemble MLAs were built based on naive bayes, random forest and support vector classifier for low risk and generalized linear regression, support vector regressor and stochastic gradient descent regressor for high risk categories. MLAs were trained on 600 Southeast Asians aged 21 to 69 years free of cardiovascular disease. All MLAs outperformed the FRS for low and high-risk categories. MLA based on lifestyle questionnaire only achieved AUC of 0.715 (95% CI 0.681, 0.750) and 0.710 (95% CI 0.653, 0.766) for low and high risk respectively. Combining all groups of risk factors (lifestyle survey questionnaires, clinical blood tests, 24-h ambulatory blood pressure and heart rate monitoring) along with feature selection, prediction of low and high CVD risk groups were further enhanced to 0.791 (95% CI 0.759, 0.822) and 0.790 (95% CI 0.745, 0.836). Besides conventional predictors, self-reported physical activity, average daily heart rate, awake blood pressure variability and percentage time in diastolic hypertension were important contributors to CVD risk classification.

Background Fecal immunochemical test (FIT) is worldwide strategy for colorectal cancer screening. The subjects with negative FIT still have the risk of an advanced colorectal neoplasia (AN), including adenoma with villous histology, high grade dysplasia or larger than 1 cm in size, or adenocarcinoma. The study determined the risk factors associated with AN in FIT-negative subjects. Methods The study included asymptomatic subjects who received health checkup colonoscopy and have provided FIT study within 6 months prior to colonoscopy. The risk factors to have AN in cases with negative FIT were analyzed. The numbers of colonoscopies needed to detect one AN were calculated for the subjects with different risk factors. Results There were 1411 cases, 85 with positive FIT and 1326 with negative FIT within 6 months before colonoscopy. In FIT positive and FIT negative cases, 45.9% and 34.6% were found to have colorectal adenoma, while 20.2% and 4.6% had AN, respectively. The univariate and multivariate logistic regression analyses showed that age more than 50 years old, male sex, smoking history and metabolic syndrome were the significant risk factors to have AN in the FIT negative cases. For cases with negative FIT to have these risk factors, the number of colonoscopies needed to detect one AN was 3.7, lower than 4.5 of the cases with positive FIT. Conclusion For the cases with negative FIT, colonoscopy screening should be considered for those male patients over 50 years old, with a history of smoking and metabolic syndrome to detect AN.

According to the 2019 World Health Organization (WHO) classification, well-differentiated grade 3 (G3) gastroenteropancreatic (GEP) neuroendocrine tumors (NETs) are a new category of cancer of the digestive system. G3 GEP-NET research and treatment are not as robust as those of lower grade (G1/2) NETs and poorly differentiated neuroendocrine carcinomas (NECs). Previously, the management of high-grade NETs was mainly based on NEC therapies, as high-grade NETs were classified as NECs under the previous WHO classification. Despite this, G3 GEP-NETs are significantly less responsive to platinum-based chemotherapy regimens than NECs, due to their distinct molecular pathogenesis and course of pathological grade transition. Patients with advanced G3 GEP-NETs, who have progressed or are intolerant to chemotherapy regimens such as capecitabine plus temozolomide, have limited treatment choices. Immunotherapy has helped patients with a variety of cancers attain long-term survival through the use of immune checkpoint inhibitors. Immunotherapies, either alone or in combination with other therapies, do not have a clear function in the treatment of G3 GEP-NETs. Currently, the majority of immunotherapy studies, both prospective and retrospective, do not reliably differentiate G3 GEP-NETs from NECs. By contrast, a significant number of studies include non-GEP neuroendocrine neoplasms (NENs). Therefore, there is an urgent need to summarize and evaluate these data to provide more effective therapeutic approaches for patients with this rare tumor. The purpose of this mini-review was to screen and summarize information on G3 GEP-NETs from all studies on NENs immunotherapy.

Objective The objective of this work was to develop a peptide production process of the exact molecular weight propitious to topical application for cosmetics and to investigate the effects of enzymolysis-derived peptide on UVB-induced photoaging rat skin. Methods The chum salmon fish skins were hydrolyzed by alkaline protease and neutral protease and spray-dried at different conditions, and three kinds of molecular weight peptide (MFSOP) were obtained. A total of 66 ICR rats (female, 20 ± 1 g) were randomly divided into eleven groups, including the normal, model, and experimental groups. The three kinds of MFSOP were dissolved at different dosages (5‰, 2.5%, and 5%) and then applied on the ICR hairless back skins prior to exposing UVB irradiation of 3000mJ/cm2 to them 4 h later. After 8 weeks, the rats were killed and the hair-shaved skins were tested for skin moisture, hyaluronic acid, hydroxyproline, antioxidant activity, and RNA expression. Results Three kinds of MFSOP were obtained, with the average molecular weights of 495.16, 1194.00, and 2032.46 Dalton, respectively. The MFSOPs, especially the MFSOP of average molecular weight of 1194.00 Dalton, played an important role in the recovery of the UVB-injured skin tissue in lock in moisture, in antioxidant activity and in promotion in collagen and elastin protein to some extent. Conclusion MFSOPs, especially MFSOP of average molecular weight of 1194.00 Dalton, derived from enzymolysis are potential materials to apply in cosmetics for the UVB9-induced anti-photoaging activity (lock in moisture, antioxidant activity, and promotion in collagen and elastin protein).

Background Patients with Rockall scores ≥6 have an increased risk of long-term peptic ulcer rebleeding. This study was aimed toward investigating whether an extended course of oral esomeprazole up to 1 year decreased ulcer rebleeding in such patients. Methods We prospectively enrolled 120 patients with peptic ulcer bleeding and Rockall scores ≥6. After an initial 16-week oral proton pump inhibitor (PPI) treatment, patients were randomized to receive a 36-week course of oral twice-daily esomeprazole 20 mg (Group D, n = 60) or once-daily (Group S, n = 60). Thereafter, they were divided into the PPI-on-demand (n = 32) and PPI-discontinued (n = 77) subgroups. Our previous cohort with Rockall scores ≥6 served as the controls (Group C, n = 135); they received only an initial 8- to 16-week oral PPI. The primary and secondary outcomes were peptic ulcer rebleeding during the first year and the second year-and-thereafter, respectively. Results For the primary outcome, groups D and S comprised a higher proportion of rebleeding-free than Group C (P = 0.008 and 0.03, log-rank test). The competing-risks regression analysis confirmed that extended PPI use and American Society of Anesthesiologists classification were independent factors contributing to the primary outcome. For the secondary outcome, PPI-on-demand had a borderline higher proportion of rebleeding-free than Group C (P = 0.07, log-rank test); however, only the Rockall score was the independent factor. Conclusions An extended 36-week course of oral esomeprazole 20 mg, twice- or once-daily for patients with Rockall scores ≥6 reduced ulcer rebleeding during the first year, but the effect needed to be further validated when PPIs were shifted to on-demand or discontinued thereafter (NCT02456012, 28/05/2015).

BackgroundEsophageal squamous cell carcinoma (ESCC) is one of the most common cancers in the world, the detection and prognosis of which are still unsatisfactory. Thus, it is essential to explore the factors that may identify ESCC and evaluate the prognosis of ESCC patients. ResultsBoth protein and mRNA expression levels of BIRC5 are upregulated in ESCC group rather than non-ESCC group (standardized mean difference > 0). BIRC5 mRNA expression is related to the age, tumor location, lymph node stage and clinical stage of ESCC patients (p < 0.05). BIRC5 expression makes it feasible to distinguish ESCC from non-ESCC (area under the curve > 0.9), and its high expression is related to poor prognosis of ESCC patients (restrictive survival time difference = -0.036, p < 0.05). BIRC5 may play an important role in ESCC by influencing the cell cycle pathway, and CDK1, MAD2L and CDC20 may be the hub genes of this pathway. The transcription factors-MAZ and TFPD1 -are likely to regulate the transcription of BIRC5, which may be one of the factors for the high expression of BIRC5 in ESCC. ConclusionsThe current study shows that upregulation of BIRC5 may have essential clinical value in ESCC, and contributes to the understanding of the pathogenesis of ESCC.

Mesothelin (MSLN) is an attractive candidate of targeted therapy for several cancers, and hence there are increasing needs to develop MSLN-targeting strategies for cancer therapeutics. Antibody–drug conjugates (ADCs) targeting MSLN have been demonstrated to be a viable strategy in treating MSLN-positive cancers. However, developing antibodies as targeting modules in ADCs for toxic payload delivery to the tumor site but not to normal tissues is not a straightforward task with many potential hurdles. In this work, we established a high throughput engineering platform to develop and optimize anti-MSLN ADCs by characterizing more than 300 scFv CDR-variants and more than 50 IgG CDR-variants of a parent anti-MSLN antibody as candidates for ADCs. The results indicate that only a small portion of the complementarity determining region (CDR) residues are indispensable in the MSLN-specific targeting. Also, the enhancement of the hydrophilicity of the rest of the CDR residues could drastically increase the overall solubility of the optimized anti-MSLN antibodies, and thus substantially improve the efficacies of the ADCs in treating human gastric and pancreatic tumor xenograft models in mice. We demonstrated that the in vivo treatments with the optimized ADCs resulted in almost complete eradication of the xenograft tumors at the treatment endpoints, without detectable off-target toxicity because of the ADCs’ high specificity targeting the cell surface tumor-associated MSLN. The technological platform can be applied to optimize the antibody sequences for more effective targeting modules of ADCs, even when the candidate antibodies are not necessarily feasible for the ADC development due to the antibodies’ inferior solubility or affinity/specificity to the target antigen.

Epidemiological studies demonstrate an association between breast cancer (BC) and systemic dysregulation of glucose metabolism. However, how BC influences glucose homeostasis remains unknown. We show that BC-derived extracellular vesicles (EVs) suppress pancreatic insulin secretion to impair glucose homeostasis. EV-encapsulated miR-122 targets PKM in β-cells to suppress glycolysis and ATP-dependent insulin exocytosis. Mice receiving high-miR-122 EVs or bearing BC tumours exhibit suppressed insulin secretion, enhanced endogenous glucose production, impaired glucose tolerance and fasting hyperglycaemia. These effects contribute to tumour growth and are abolished by inhibiting EV secretion or miR-122, restoring PKM in β-cells or supplementing insulin. Compared with non-cancer controls, patients with BC have higher levels of circulating EV-encapsulated miR-122 and fasting glucose concentrations but lower fasting insulin; miR-122 levels are positively associated with glucose and negatively associated with insulin. Therefore, EV-mediated impairment of whole-body glycaemic control may contribute to tumour progression and incidence of type 2 diabetes in some patients with BC.

Objectives To evaluate the utility of the splenial angle (SA), an axial angular index of lateral ventriculomegaly measured on diffusion tensor MRI color fractional anisotropy maps, in differentiating NPH from Alzheimer’s disease (AD), Parkinson’s disease (PD), and healthy controls (HC), and post-shunt changes in NPH, compared to Evans’ index and callosal angle. Methods Evans’ index, callosal angle, and SA were measured on brain MRI of 76 subjects comprising equal numbers of age- and sex-matched subjects from each cohort of NPH, AD, PD, and HC by two raters. Receiver operating characteristics (ROC) and multivariable analysis were used to assess the screening performance of each measure in differentiating and predicting NPH from non-NPH groups respectively. Temporal changes in the measures on 1-year follow-up MRI in 11 NPH patients (with or without ventriculoperitoneal shunting) were also assessed. Results Inter-rater and intra-rater reliability were excellent for all measurements (intraclass correlation coefficients > 0.9). Pairwise comparison showed that SA was statistically different between NPH and AD/PD/HC subjects (p < 0.0001). SA performed the best in predicting NPH, with an area under the ROC curve of > 0.98, and was the only measure left in the final model of the multivariable analysis. Significant (p < 0.01) change in SA was seen at follow-up MRI of NPH patients who were shunted compared to those who were not. Conclusions The SA is readily measured on axial DTI color FA maps compared to the callosal angle and shows superior performance differentiating NPH from neurodegenerative disorders and sensitivity to ventricular changes in NPH after surgical intervention. Key Points • The splenial angle is a novel simple angular radiological index proposed for idiopathic normal pressure hydrocephalus, measured in the ubiquitous axial plane on DTI color fractional anisotropy maps. • The splenial angle quantitates the compression and stretching of the posterior callosal commissural fibers alongside the distended lateral ventricles in idiopathic normal pressure hydrocephalus (NPH) using tools readily accessible in clinical practice and shows excellent test-retest reliability. • Splenial angle outperforms Evans’ index and callosal angle in predicting NPH from healthy, Parkinson’s disease, and Alzheimer’s disease subjects on ROC analysis with an area under the curve of > 0.98 and is sensitive to morphological ventricular changes in NPH patients after ventricular shunting.

Thyroxine (T4) importantly regulates the growth of newborns. Compared to fetuses with equivalent gestational ages, very preterm infants (VPIs) often experience relatively low thyroxinemia, with a normal thyroid-stimulating hormone (TSH) concentration < 10 μIU/mL. However, there is continued debate regarding postnatal thyroxine supplementation for VPIs with normal TSH and transitionally low thyroxinemia. Little research has explored the role of the postnatal total T4 (TT4) serum concentration on the growth of VPIs. In this study, we aim to clarify whether the postnatal thyroxine concentration is associated with the short- and long-term growth outcomes of VPIs. A total of 334 surviving VPIs in our previously reported cohort, born in the period August 2007–July 2016, were enrolled. The exposure variable was the postnatal TT4 concentration at 1 month old. The primary outcomes were body weight increments over 28 days after the screening and anthropometric outcomes at the corrected age of 24 months old. Infants with any hormonal replacement, severe brain injury, congenital anomaly, or cerebral palsy were excluded. In total, 290 (86.8%) VPIs were included for analysis. In the 28 days after thyroid function screening, the TT4 concentration was found to have a significant association with positive increments in body weight (mean increment: 25.7 g per 1 μg/dL; p < 0.001) and a positive body weight z-score (mean increment: 0.039 per 1 μg/dL; p = 0.037), determined by generalized estimating equation analysis. At the corrected age of 24 months old, a higher postnatal TT4 concentration was associated with a lower body mass index (mean coefficient: −0.136; 95% CI: −0.231 to −0.041, p = 0.005) and lower body mass index z-score (mean coefficient: −0.097; 95% CI: −0.170 to −0.024, p = 0.009). Infants with a TT4 concentration > 6.4 ug/dL had significantly lower odds of overweight status (odds ratio: 0.365; 95% CI: 0.177 to 0.754, p = 0.006). We conclude that the postnatal TT4 concentration is associated with a positive increment in body weight in the short term. At the same time, the postnatal TT4 concentration is associated with lower odds of overweight status after long-term follow-up.

Sub-Saharan Africa has the highest HIV incidence and prevalence in the world. In the past decade, mobile phone ownership has doubled, affecting social and sexual practices. Using longitudinal follow-up data, this study examined whether mobile phone ownership was associated with sexual behaviors and HIV incidence for youth and adults.The Rakai Community Cohort Study gathers demographic and sexual health information and conducts HIV testing among an open cohort in southcentral Uganda every 12-18 months.Of the 10,618 participants, 58% owned a mobile phone, 69% lived in rural locations, and 77% were sexually active. Analyses were adjusted for time, location, religion, and socioeconomic status. Phone ownership was associated with increased odds of ever having had sex act for 15- to 19-year-olds [men adjusted odds ratio (AOR): 2.12, 95% confidence interval (CI): 1.78 to 2.52; women AOR: 3.20, 95% CI: 2.45 to 4.17]. Among sexually active participants, owning a phone was associated with increased odds of having 2 or more concurrent sex partners (15- to 24-year-old men AOR: 1.76, 95% CI: 1.34 to 2.32; 25 to 49-year-old men: AOR 1.81, 95% CI: 1.54 to 2.13; 25- to 49-year-old women AOR: 1.81, 95% CI: 1.32 to 2.49). For men, phone ownership was associated with increased odds of circumcision (15- to 24-year-old men AOR: 1.24, 95% CI: 1.08 to 1.41; 25- to 49-year-old men AOR: 1.12, 95% CI: 1.01 to 1.24). Phone ownership was not associated with HIV incidence.Although mobile phone ownership was associated with sexual risk behaviors, it was not associated with increased risk of HIV acquisition. Research should continue exploring how phones can be used for reducing sexual health risk.

During the pandemic of the coronavirus disease 2019, there exist quite a few studies on angiotensin-converting enzyme 2 (ACE2) and SARS-CoV-2 infection, while little is known about ACE2 in hepatocellular carcinoma (HCC). The detailed mechanism among ACE2 and HCC still remains unclear, which needs to be further investigated. In the current study with a total of 6,926 samples, ACE2 expression was downregulated in HCC compared with non-HCC samples (standardized mean difference = −0.41). With the area under the curve of summary receiver operating characteristic = 0.82, ACE2 expression showed a better ability to differentiate HCC from non-HCC. The mRNA expression of ACE2 was related to the age, alpha-fetoprotein levels and cirrhosis of HCC patients, and it was identified as a protected factor for HCC patients via Kaplan–Meier survival, Cox regression analyses. The potential molecular mechanism of ACE2 may be relevant to catabolic and cell division. In all, decreasing ACE2 expression can be seen in HCC, and its protective role for HCC patients and underlying mechanisms were explored in the study., Graphical Abtstract

The screening and treatment of laryngeal squamous cell carcinoma (LSCC) still perplexes clinicians, making it necessary to explore new markers. To this end, this research examined the underlying molecular mechanism of LSCC based on high-throughput datasets (n = 249) from multiple databases. It also identified transcription factors (TFs) independently associated with LSCC prognosis. Through Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses, differential expression genes of LSCC were deemed relevant to the extracellular matrix and its related structures or pathways, suggesting that the extracellular matrix plays an important role in LSCC. At the same time, several hub genes that may also have important roles in LSCC were identified via protein–protein interaction analysis, including CDC45, TPX2, AURKA, KIF2C, NUF, MUC1, MUC7, MUC4, MUC15, and MUC21. Eight unreported LSCC prognostic TFs – BCAT1, CHD4, FOXA2, GATA6, HNF1A, HOXB13, MAFF, and TCF4 – were screened via Kaplan–Meier curves. Cox analysis determined for the first time that HOXB13 expression and gender were independently associated with LSCC prognosis. Compared to control tissues, elevated expression of HOXB13 was found in LSCC tissues (standardized mean difference = 0.44, 95% confidence interval [0.13–0.76]). HOXB13 expression also makes it feasible to screen LSCC from non-LSCC (area under the curve = 0.77), and HOXB13 may play an essential role in LSCC by regulating HOXB7. In conclusion, HOXB13 may be a novel marker for LSCC clinical screening and treatment.

Synaptojanin 2 (SYNJ2) regulates cell proliferation and apoptosis via dephosphorylating plasma membrane phosphoinositides. Aim of this study is to first seek the full-scale expression levels and potential emerging roles of SYNJ2 in hepatocellular carcinoma (HCC). We systematically analyzed SYNJ2 mRNA expression and protein levels in HCC tissues based on large-scale data and in-house immunohistochemistry (IHC). The clinical significance and risk factors for SYNJ2-related HCC cases were identified. A nomogram of prognosis was created and its performance was validated by concordance index (C-index) and shown in calibration plots. Based on the identified differentially coexpressed genes (DCGs) of SYNJ2, enriched annotations and potential pathways were predicted, and the protein interacting networks were mapped. Upregulated SYNJ2 in 3,728 HCC and 3,203 non-HCC tissues were verified and in-house IHC showed higher protein levels of SYNJ2 in HCC tissues. Pathologic T stage was identified as a risk factor. Upregulated mRNA levels and mutated SYNJ2 might cause a poorer outcome. The C-index of the nomogram model constructed by SYNJ2 level, age, gender, TNM classification, grade, and stage was evaluated as 0.643 (95%CI = 0.619–0.668) with well-calibrated plots. A total of 2,533 DCGs were extracted and mainly functioned together with SYNJ2 in metabolic pathways. Possible transcriptional axis of CTCF/POLR2A-SYNJ2/INPP5B (transcription factor-target) in metabolic pathways was discovered based on ChIP-seq datasets. In summary, transcriptional regulatory axis CTCF/POLR2A-SYNJ2 might influence SYNJ2 expression levels. Increased SYNJ2 expression level could be utilized for predicting HCC prognosis and potentially accelerates the occurrence and development of HCC via metabolic perturbations pathways., Graphical abstract

To explain the clinicobiological heterogeneity of NPM1 mutated (NPM1Data of 238 NPM1In entire NPM1Co-existing FLT3-ITD in NPM1伴NPM1突变急性髓系白血病二代测序突变基因谱与MICM分型特征关联性分析.分析伴NPM1突变（NPM1收集苏州大学附属第三医院、南京医科大学附属常州第二人民医院和浙江医院收治的成人初诊AML患者，选取NGS资料完整的NPM1全部患者共检出240个NPM1突变事 件，其中10个（10/240，4.2%）为错义突变，均不累及W288或W290位点。这10例错义突变事件仅见于NPM1NPM1

To investigate the effects of decitabine (DEC) combined with all-trans retinoic acid (ATRA) on the number of immune cells, efficacy and adverse reactions in the treatment of myeloid neoplasms patients.Eighty-four patients with myeloid tumors, including AML, MDS-EB-1 or MDS-EB-2 treated by the regimen containing decitabine in our hospital from January 2009 to October 2019 were enrolled and retrospectively analyzed, among the patients, 21 patients treated with DEC alone, 24 patients treated with DEC combined with ATRA (DEC/ATRA) and 39 patients treated with DEC combined with G-CSF priming regimen (DEC/priming). The changes of peripheral blood immune cell levels before and after treatment of the patients between the three groups were compared, and the differences in clinical efficacy and adverse reactions of the patients between the three groups were also compared.There was no statistical differences in the number of immune cells among the patients in the three groups before treatment (P0.05). NK cell levels decreased significantly in the patients in DEC and DEC/ATRA group after treatment (P0.05); After treatment, the levels of CD8+ and CD3+T cells in the patients treated by DEC /priming regimen significantly increased (P0.05), while the levels of CD3-HLA-DR+ B cells significantly decreased (P0.05). The overall response rate (ORR) of the patients in DEC/ATRA group (75%) and DEC/priming group (74.36%) was significantly higher than 42.86% in DEC monotherapy group, and the differences showed statistically significant (P0.05), while the ORR between the patients in DEC/ATRA and DEC/priming group showed no statistic differences (P0.05). There were no statistical differences in overall survival (OS) and incidence of bleeding between the patients in the three groups (P0.05). The incidences of grade 3 to 4 bone marrow suppression and the infection rate of the patients in DEC monotherapy and DEC/ATRA group were significantly lower than that in DEC/priming regimen group after treatment (all P0.05), however, there was no statistical difference between DEC monotherapy and the DEC/ATRA group.The efficacy of DEC/ATRA on myeloid neoplasms is comparable to that of DEC/priming regimen, and the anti-myeloid tumor effect of DEC/ATRA regimen may be related to the regulation of NK cells and T cells.地西他滨联合全反式维甲酸治疗髓系肿瘤患者 免疫细胞水平变化的研究.探讨地西他滨（DEC）联合全反式维甲酸（ATRA）治疗髓系肿瘤患者过程中，免疫细胞数量变化及疗效与安全性.选取并回顾性分析2009年1月至2019年10月于常州市第一人民医院住院接受DEC治疗的髓系肿瘤患者84例，包括急性髓系白血病（AML）、骨髓增生异常综合征伴原始细胞增多（MDS-EB-1或MDS-EB-2），其中DEC单药组21例、DEC联合ATRA组24例及DEC联合预激方案组39例。比较3组患者治疗前后外周血免疫细胞水平的变化、临床疗效及不良反应差异.3组患者治疗前免疫细胞数量比较无统计学差异（P0.05）。DEC单药组及DEC联合ATRA组患者治疗后NK细胞水平明显下降（P0.05），DEC联合预激方案组患者治疗后CD8+及CD3+T细胞水平明显上升，而CD3-HLA-DR+的B细胞水平下降，且上述差异均有统计学意义（P0.05）。DEC联合ATRA组及DEC联合预激组的总体有效率（ORR）分别为75%和74.36%，均显著高于DEC单药组的42.86%（P0.05），而DEC联合ATRA组与DEC联合预激组的ORR无统计学差异（P0.05）。3组患者OS无统计学差异（P0.05）。3组患者治疗后出血发生率均无统计学差异（P0.05）。DEC单药组及DEC联合ATRA组治疗后3-4级骨髓抑制发生率及感染率明显低于DEC联合预激组（P0.05），而DEC单药组与DEC联合ATRA组治疗后3-4级骨髓抑制发生率及感染率无统计学差异.DEC联合ATRA方案治疗髓系肿瘤的疗效与DEC联合预激方案相当，其抗髓系肿瘤的作用可能与其对NK细胞及T细胞的调控有关.

This study is conducted to explore the association between health behaviors and the COVID-19 vaccination based on the risk compensation concept among health-care workers in Taizhou, China. We conducted a self-administered online survey to estimate the health behaviors among the staff in a tertiary hospital in Taizhou, China, from May 18 to 21 May 2021. A total of 592 out of 660 subjects (89.7%) responded to the questionnaire after receiving an e-poster on WeChat. Subjects who had been inoculated with the COVID-19 vaccine were asked to mention the differences in their health behaviors before and after the vaccination. The results showed that there were no statistical differences in health behaviors between vaccinated and unvaccinated groups, except in terms of the type of gloves they used (62.8% in the vaccinated group and 49.2% in the unvaccinated group

The COVID-19 outbreak was declared a public health emergency of international concern by the World Health Organization on January 30, 2020. Since then, the virus has spread to affect more countries worldwide. During this period, our nuclear medicine department at Singapore General Hospital segregated our staff and patients by time, by space, or both, to minimize contact and prevent spread of the virus. Necessary changes to our clinical practices and stricter infection control measures were also enforced. We share our personal experience in managing a nuclear medicine department during this epidemic.

Pulmonary embolism (PE) care has traditionally been fragmented. The newly introduced Pulmonary Embolism Response Team (PERT) model provides streamlined care based on expedient, multi-disciplinary decision-making. This study aimed to quantify the impact of PERT, as part of a hospital-wide PE treatment protocol, on clinical outcomes.Consecutive adult patients with acute PE diagnosed via computed tomography pulmonary angiogram (CTPA) were included. The PERT and treatment protocol were introduced in January 2015. Patient characteristics, therapies, quality measures of CTPA reporting, and clinical outcomes of PE patients treated for 2 years before and after implementation of these changes were evaluated. Primary endpoints were median length of stay in intensive care (ICU) and survival to discharge.A total of 321 consecutive PE patients were enrolled, of which 154 (treated in 2013-2014) and 167 (2015-2016) patients formed the historical control and study groups, respectively. Implementation of the algorithm was associated with less variance in anticoagulation and improved reporting of right heart strain parameters on CTPA. The ICU stay was reduced from a median of 5 to 2 days (p 0.01). Eligible massive PE patients receiving reperfusion increased from 30% to 92% (p = 0.01), with mean delay from diagnosis to reperfusion decreasing from 763 to 181 minutes (p 0.01). Bleeding complications were not increased, but overall survival to discharge remained unchanged.Introducing a PERT and treatment protocol reduced ICU stay, enhanced quality measures, and improved access of massive PE patients to reperfusion therapies, without increasing bleeding complications or health care costs.

The antidiabetic effect of different doses of water extract (WE) and ethanol extract (EE) was tested on a high-fat diet and streptozotocin (STZ) induced diabetic rats. Parameters were evaluated with normal control (NC), diabetes mellitus control (DM), and metformin (M) groups. In the experiment, nine groups were used with eight rats in each group and three doses of each WE and EE were used, with low, medium, and high doses. The results revealed that the DM group lost a significant amount of weight, whereas the NC group's weight increased throughout the experiment. After treatment with Fomitopsis pinicola, the EE group's weight increased gradually. Liver, kidney, and pancreas weight decreased after STZ injection and returned to normal in EE treated groups. Fasting blood glucose (FBG) levels were observed to be significantly lower after F. pinicola treatment. Serum insulin levels were also restored to normal after mushroom extracts supplementation. Specifically, STZ-induced hyperglycemia was inhibited by high dose EE administration. The biochemical analysis revealed that high-dose EE treatment increased HDL-C and decreased TC, TG, and LDL-C. Results demonstrated that high-dose EE administration protected the organ tissues from oxidative stress by normalizing the antioxidant levels, and CAT, SOD, and GSH-Px suppressed the lethal effect of MDA. The study concluded that F. pinicola EE at the dose 300 mg/kg has a more hypoglycemic, hyperinsulinemic, antioxidant, and antihyperlipidemic effect than NC, DM, and M, and regulates hyperglycemia by increasing insulin secretion.

Objective: In this study, we investigated the changes in peripheral blood inflammatory factors and intestinal flora in acquired immune deficiency syndrome (AIDS) and human immunodeficiency virus (HIV)-positive individuals (AIDS/HIV patients), and explored the relationships among intestinal flora, peripheral blood inflammatory factors, and CD4(+) T lymphocytes. Methods: Thirty blood and stool samples from an AIDS group and a control group were collected. The levels of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) were determined by enzyme-linked immunosorbent assay (ELISA), and the number of CD4(+) T lymphocytes by a FACSCount automated instrument. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to determine the messenger RNA (mRNA) levels of Bifidobacterium, Lactobacillus, Escherichia coli, Enterococcus faecalis, and Enterococcus faecium. Correlations among intestinal flora, inflammatory factor levels, and CD4(+) T lymphocyte values were evaluated using the Spearman correlation coefficient. Results: The levels of TNF-α and IL-6 in the AIDS group were higher than those in the control group, while the number of CD4(+) T lymphocytes was lower. The amounts of Bifidobacterium and Lactobacillus in the AIDS group were significantly lower than those in control group, while the amounts of E. coli, E. faecalis, and E. faecium were much higher. The amounts of Bifidobacterium and Lactobacillus were negatively correlated with the content of TNF-α and IL-6 and the CD4(+) T lymphocyte count, while those correlations were reversed for E. coli, E. faecalis, and E. faecium. Conclusions: The intestinal microbiota of AIDS/HIV patients were disordered, and there was a correlation between the amount of intestinal flora and the number of CD4(+) T lymphocytes and the levels of TNF-α and IL-6.

There are abundant natural diterpenoids in the plants of the genus Daphne from the Thymelaeaceae family, featuring a 5/7/6-tricyclic ring system and usually with an orthoester group. So far, a total of 135 diterpenoids has been isolated from the species of the genus Daphne, which could be further classified into three main types according to the substitution pattern of ring A and oxygen-containing functions at ring B. A variety of studies have demonstrated that these compounds exert a wide range of bioactivities both in vitro and in vivo including anticancer, anti-inflammatory, anti-HIV, antifertility, neurotrophic, and cholesterol-lowering effects, which is reviewed herein. Meanwhile, the fascinating structure–activity relationship is also concluded in this review in the hope of providing an easy access to available information for the synthesis and optimization of efficient drugs.

Epstein-Barr virus-related hemophagocytic lymphohistiocytosis (EBV-HLH) is a life-threatening hyperinflammatory syndrome. Although etoposide-based immunochemotherapy has improved survival rates, consensus regarding the appropriate salvage therapy for patients with refractory or relapsed EBV-HLH is lacking. We performed a retrospective study to examine the efficacy of a lymphoma-based treatment regimen for children with refractory or relapsed EBV-HLH. The data of six children were analyzed. Four had cytogenetic abnormalities, and two experienced a transition to EBV-positive T-cell lymphoma. They were treated with an intensive chemotherapy regimen modified from that used in the Berlin-Frankfurt-Münster Group Trial as salvage therapy. Five patients (83%) achieved complete response. Four patients (67%) were disease free for a median of 10 years without undergoing allogeneic hematopoietic stem cell transplantation. No grade 3 or 4 nonhematologic adverse events occurred. Lymphoma-based chemotherapy is a potential curative treatment for some subgroups of children with refractory or relapsed EBV-HLH.

Exosomes are nanoparticles secreted by all cell types and are a large component of the broader class of nanoparticles termed extracellular vesicles (EVs). Once secreted, exosomes gain access to the interstitial space and ultimately the circulation, where they exert local paracrine or distal systemic effects. Because of this, exosomes are important components of an intercellular and intraorgan communication system capable of carrying biologic signals from one cell type or tissue to another. The exosomal cargo consists of proteins, lipids, miRNAs, and other RNA species, and many of the biologic effects of exosomes have been attributed to miRNAs. Exosomal miRNAs have also been used as disease biomarkers. The field of exosome biology and metabolism is rapidly expanding, with new discoveries and reports appearing on a regular basis, and it is possible that potential therapeutic approaches for the use of exosomes or miRNAs in metabolic diseases will be initiated in the near future.

A community-based prostate cancer screening program was conducted to assess the morbidity and associated factors for prostate cancer among the subpopulation of men aged ≥50 years in Taizhou, China. Taizhou Integrated Prostate Screening (TIPS) is a large, observational, population-based study of prostate cancer screening data based on serum prostate-specific antigen (PSA) concentrations. A pilot census of all male residents aged 50 years or older was conducted in Luqiao District, one of the field sites of the TIPS cohort in the city of Taizhou, Zhejiang. The interviewer-administered questionnaire evaluated demographic characteristics and environmental exposure factors. A total of 1,806 out of 3,516 participants completed the questionnaire. The overall prevalence of PSA ≥4 ng/mL was 11.5%, and included participants at low risk (9.2%), moderate risk (1.7%), and high risk (0.6%). Participants aged 60–69, 70–79, and ≥80 years had a 2.7-fold, 4.2-fold, and 6.5-fold higher risk of elevated PSA, respectively, in comparison with those aged 50 to 59 years ( p < .001). Eighteen patients were diagnosed with prostate cancer, of whom 11 (61.1%) underwent radical surgery. This community-based PSA screening program indicated the results for early detection of prostate cancer among men aged ≥50 years. Early screening and appropriate clinical therapy for the management of prostate cancer are essential in this subpopulation.

BackgroundPediatric burns of all the ages are prevalent worldwide, posing a severe health risk to children. This study aims to examine pediatric burns' clinical characteristics and epidemiology in central China.MethodsThe pediatric patients of the Burn Research Center, Department of the First People's Hospital of Zhengzhou City from 2013 to 2019 were retrospectively studied and the relevant data were collected from the hospitalized medical records [e.g., demographic, etiology, length of stay (LOS), age, gender, burn area and depth, number of surgeries, cost, and outcome].ResultsA total of 5,569 pediatric burn patients were included, accounting for 43.9% of the total burn population. Electric burns represented a relatively small proportion (1.17%) but were more likely to lead to disabilities or death than scalds (90.63%) and flames (5.12%). The median age was 2 years [interquartile range (IQR): 1–4] and the boys/girls ratio ranged from 1.3:1 to 1.6:1. The most commonly burnt anatomic sites were the limbs (38.3%), with a median %TBSA (total body surface area) of 6 (IQR: 4–10). The complications of shock and pneumonia accounted for 7.6 and 19.2%, respectively. The peak months of pediatric burns included January, May, and August and the rural/urban ratio reached 1.61:1. The percentage of burn wounds treated surgically increased considerably from 2013 to 2019 (3.8 vs. 37.8%). The median hospital LOS was 15 days (IQR: 8–28 days), with the three high-risk factors (e.g., more surgeries, more %TBSA, full-thickness skin burns). The median cost of hospitalization was 1,511 USD (IQR: 848–2,648 USD) and the main risk factors consisted of full-thickness burns, more %TBSA, longer LOS, and more surgical procedures. Among all the patients, LA50 was 78.63% (95% CI = 75.12–83.45) and the overall mortality reached 0.1% since seven deaths were recorded.ConclusionScalds, flames, contact, and chemicals are the main causes of burns among children aged 1–5 years in central China. Accordingly, various prevention strategies should be employed depending upon the cause of the burn.

Background Clinical trials have demonstrated that initiating oral anti-diabetic drugs (OADs) significantly reduce glycated hemoglobin (HbA1c) levels. However, variability in lifestyle modifications and OAD adherence impact on their actual effect on glycemic control. Furthermore, evidence on dose adjustments and discontinuation of OAD on HbA1c is lacking. This study aims to use real-world data to determine the effect of OAD initiation, up-titration, down-titration, and discontinuation on HbA1c levels, among Asian patients managed in primary care. Methods A retrospective cohort study over a 5-year period, from Jan 2015 to Dec 2019 was conducted on a cohort of multi-ethnic adult Asian patients with clinical diagnosis of type 2 diabetes mellitus (T2DM) managed by a network of primary care clinics in Singapore. Nine OADs from five different classes (biguanides, sulphonyurea, dipeptidyl peptidase-4 [DPP-4] inhibitors, sodium-glucose cotransporter-2 [SGLT-2] inhibitors, and alpha-glucosidase inhibitors) were evaluated. Patients were grouped into “No OAD”, “Non-titrators,” and “Titrators” cohorts based on prescribing patterns. For the “Titrators” cohort, the various OAD titrations were identified. Subsequently, a descriptive analysis of HbA1c values before and after each titration was performed to compute a mean difference for each unique titration identified. Results Among the cohort of 57,910 patients, 43,338 of them had at least one OAD titration, with a total of 76,990 pairs of HbA1c values associated with an OAD titration. There were a total of 206 unique OAD titrations. Overall, initiation of OADs resulted in a reduction of HbA1c by 3 to 12 mmol/mol (0.3 to 1.1%), respectively. These results were slightly lower than those reported in clinical trials of 6 to 14 mmol/mol (0.5 to 1.25%). The change of HbA1c levels due to up-titration, down-titration, and discontinuation were −1 to −8 mmol/mol (−0.1 to −0.7%), +1 to 7 mmol/mol (+0.1 to +0.6%), and +2 to 11 mmol/mol (+0.2 to +1.0%), respectively. The HbA1c lowering effect of initiating newer OADs, namely DPP-4 inhibitors and SGLT-2 inhibitors was 8 to 11 mmol/mol (0.7 to 0.9%) and 7 to 11 mmol/mol (0.6 to 1.0%), respectively. Conclusion The real-world data on Asians with T2DM in this study show that the magnitudes of OAD initiation and dose titration are marginally lower than the results from clinical trials. During shared decision-making in selecting treatment options, the results enable physicians to communicate realistic expectation of the effect of oral medications on the glycemic control of their patients in primary care.

LncRNA SET-binding factor 2 (SBF2) antisense RNA1 (SBF2-AS1) has been proven to play an oncogenic role in various types of tumors, but the prognostic role of SBF2-AS1 in tumors, especially in diffuse lower-grade glioma (LGG), is still unclear. Here, we aimed to investigate the prognostic value of SBF2-AS1 in LGG. The LGG expression profiles from The Cancer Genome Atlas (TCGA, n = 524) and Chinese Glioma Genome Atlas (CGGA, n = 431) were mined by Kaplan-Meier analysis, Cox regression analysis, Chi-square test and GSEA analysis. Through Kaplan-Meier analysis, we found the prognosis of LGG patients with high expression of SBF2-AS1 were worse than that of patients with low expression (Log Rank P < 0.001). Cox analysis showed SBF2-AS1 was an independent prognostic factor for poorer overall survival in LGG ( P < 0.05). SBF2-AS1 was found to be significantly related to IDH mutation status and SBF2-AS1 was highly expressed in IDH wildtype group. GSEA analysis obtained a total of 126 GO terms and 6 KEGG pathways that were significantly enriched in SBF2-AS1 high expression phenotype (NOM P value < 0.05). We found these 126 GO terms and KEGG pathways were mainly related to immunity. In conclusion, lncRNA SBF2-AS1 expression is an immune-related lncRNA associated with unfavorable overall survival in LGG. SBF2-AS1 could be a reliable prognostic biomarker for patients with LGG.

Background: Current studies suggest that vitamin D deficiency during pregnancy can produce a certain effect for preterm birth (PTB), but there is no research showing whether vitamin D deficiency has a consistent effect in different pregnancies; thus, we conducted a systematic review and meta-analysis of 24 observational studies, grouping them according to the gestational age at the time of serum sampling, to investigate whether vitamin D deficiency in different periods of gestation has different effects on PTB and to provide an evidence-based basis for pregnant women to measure and supplement vitamin D. Methods: The databases PubMed-Medline, EMBASE, the Cochrane Library, Web of Science, EBSCO, CBM, and CNKI were searched until February 2020. Two researchers independently assessed the eligibility and quality of studies, and STATA 12.0 software was used for meta-analysis. Result: Seven cohort studies, 13 case–control studies, and 4 cross-sectional studies were included from 2500 articles by inclusion and exclusion criteria. After adjusting for age, race, and other confounding factors, meta-analysis results showed that vitamin D deficiency in the first trimester, the second trimester, and the third trimester did not increase the risk of PTB (odds ratio (OR) = 1.01, 95% confidence interval (CI) (0.88, 1.16), P = .867; OR = 1.12, 95%CI (0.92, 1.37), P = .249; OR = 1.05, 95%CI (0.87, 1.27), P = .602). However, there was moderate heterogeneity in the study of vitamin D deficiency in the second trimester, and subgroup analysis suggested that vitamin D deficiency in the second trimester may increase the risk of PTB (OR = 1.33, 95%CI (1.15, 1.54), P = .000). A sensitivity analysis of the second trimester showed that excluding any 1 study did not significantly change the results. Conclusions: Vitamin D deficiency in early and late pregnancy may not be associated with PTB, while vitamin D deficiency in middle pregnancy is likely to have an important effect on PTB. Vitamin D levels should be measured in the second trimester of pregnancy, and vitamin D supplements should be provided if necessary.

Background and AimsA leaky gut barrier has been implicated in the initiation and progression of a multitude of diseases, e.g., inflammatory bowel disease, irritable bowel syndrome, celiac disease, and colorectal cancers. Here we asked how Chromogranin A (CgA), a major hormone produced by the enteroendocrine cells, and Catestatin (CST), the most abundant CgA-derived proteolytic peptide, affect the gut barrier. Methods and ResultsUltrastructural studies on the colons from Catestatin (CST: hCgA352-372) knockout (CST-KO) mice revealed (i) altered morphology of tight (TJ) and adherens (AJ) junctions and desmosomes, indicative of junctional stress and (ii) an increased infiltration of immune cells compared to controls. Flow cytometry studies confirmed these cells to be macrophages and CD4+ T cells. Gene expression studies confirmed that multiple TJ-markers were reduced, with concomitant compensatory elevation of AJ and desmosome markers. Consistently, the levels of plasma FITC-dextran were elevated in the CST-KO mice, confirming leakiness of the gut. Leaky gut in CST-KO mice correlated with inflammation and a higher ratio of Firmicutes to Bacteroidetes, a dysbiotic pattern commonly encountered in a multitude of diseases. Supplementation of CST-KO mice with recombinant CST reversed this leakiness and key phenotypes. Supplementation of CgA-KO mice with either CST alone, or with the pro-inflammatory proteolytic CgA fragment pancreastatin (PST: CgA250-301) showed that gut permeability is regulated by the antagonistic roles of these two peptide hormones: CST reduces and PST increases leakiness. ConclusionWe conclude that the enteroendocrine cell-derived hormone, CgA regulates gut permeability. CST is both necessary and sufficient to reduce the leakiness. CST acts primarily via antagonizing the effects of PST. What you need to knowO_ST_ABSBackground and ContextC_ST_ABSThe intestinal barrier is disrupted in many intestinal diseases such as Crohns disease. Chromogranin A (CgA) is produced by enteroendocrine cells in the gut. CgA is proteolytically cleaved into bioactive peptides including catestatin (CST) and pancreastatin (PST). The role of CgA in the gut is unknown. New findingsCgA is efficiently processed to CST in the gut and this processing might be decreased during active Crohns disease. CST promotes epithelial barrier function and reduces inflammation by counteracting PST. LimitationsThe complete mechanism of intestinal barrier regulation by CST likely involves a complex interplay between the enteroendocrine system, metabolism, the epithelium, the immune system and the gut microbiota. ImpactOur findings indicate that CST is a key modulator of the intestinal barrier and immune functions that correlates with disease severity of Crohns disease. CST could be a target for therapeutic interventions in Crohns disease.

Rationale Neutrophils constitute massive cellular constituents in inflammatory human gastric cancer (GC) tissues, but their roles in pathogenesis of inflammatory T helper (Th) subsets are still unknown. Methods Flow cytometry analysis and immunohistochemistry were used to analyze the responses and phenotypes of neutrophils in different samples from 51 patients with GC. Kaplan‐Meier plots and Multivariate analysis for the survival of patients were used by log‐rank tests and Cox proportional hazards models. Neutrophils and CD4+ T cells were purified and cultured for ex vivo, in vitro and in vivo regulation and function assays. Results GC patients exhibited increased tumoral neutrophil infiltration with GC progression and poor patient prognosis. Intratumoral neutrophils accumulated in GC tumors via CXCL6/CXCL8‐CXCR1‐mediated chemotaxis, and expressed activated molecule CD54 and co‐signaling molecule B7‐H2. Neutrophils induced by tumors strongly expressed CD54 and B7‐H2 in both dose‐ and time‐dependent manners, and a close correlation was obtained between the expressions of CD54 and B7‐H2 on intratumoral neutrophils. Tumor‐derived tumor necrosis factor‐α (TNF‐α) promoted neutrophil activation and neutrophil B7‐H2 expression through ERK‐NF‐κB pathway, and a significant correlation was found between the levels of TNF‐α and CD54+ or B7‐H2+ neutrophils in tumor tissues. Tumor‐infiltrating and tumor‐conditioned neutrophils effectively induced IL‐17A‐producing Th subset polarization through a B7‐H2‐dependent manner ex vivo and these polarized IL‐17A‐producing Th cells exerted protumorigenic roles by promoting GC tumor cell proliferation via inflammatory molecule IL‐17A in vitro, which promoted the progression of human GC in vivo; these effects could be reversed when IL‐17A is blocked. Moreover, increased B7‐H2+ neutrophils and IL‐17A in tumors were closely related to advanced GC progression and predicted poor patient survival. Conclusion We illuminate novel underlying mechanisms that TNF‐α‐activated neutrophils link B7‐H2 to protumorigenic IL‐17A‐producing Th subset polarization in human GC. Blocking this pathological TNF‐α‐B7‐H2‐IL‐17A pathway may be useful therapeutic strategies for treating GC., Our results illuminate a novel mechanism that TNF‐α‐activated neutrophils link B7‐H2 to protumorigenic IL‐17A‐producing Th subset polarization in human GC. Blocking this pathological TNF‐α‐B7‐H2‐IL‐17A pathway may be useful therapeutic strategies for treating GC.

A 61-year-old woman with well-differentiated thyroid cancer underwent 124I-PET/CT imaging. A 124I capsule was administered orally, and the patient was imaged 90 minutes after from the skull vertex to feet. The 124I capsule was unexpectedly lodged in the esophagus. We illustrate attenuation and scatter correction artifacts from 124I capsule unexpectedly lodged in the esophagus and the usefulness of nonattenuation correction images in such circumstances. This also highlights the importance of drinking adequate amounts of water following the ingestion of iodine capsules (123I, 124I, or 131I) to reduce the resulting radiation dose to the esophagus.