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Objectives An anal fistula is an external abnormal anatomical connection between the rectum and the outer skin of the anus. Symptoms include anorectal pain, abscesses, perianal cellulitis, smelly or bloody drainage of pus, and, in some cases, difficulty controlling bowel movements. Diagnosis and evaluation of anal fistulas is crucial for prognosis and for the choice of the treatment method. In this study, we aimed to discover potential biomarkers from serum proteins for the prediction of anal fistulas. Methods Using antibody array technology, the expression of 40 proteins was simultaneously detected in serum samples from 13 patients with anal fistulas with chronic diarrhea, 14 patients with chronic diarrhea and six healthy volunteers. Differentially expressed proteins were subsequently validated by ELISA, with a sample population expanded to 30 patients with anal fistulas and chronic diarrhea, 30 patients with chronic diarrheas only and 20 healthy controls. Results Quantification analysis identified MIP-1α, MIP-1β and TNF-R1 with significant differential expression between the anal fistula with chronic diarrhea, chronic diarrhea only and healthy control groups. Bioinformatics analyses, including PCA and heat map creation, showed a clear separation between the three groups using the expression of MIP-1α, MIP-1β and TNF-R1. Validation by ELISA with the expanded sample population fistulas showed significant differential expression levels of MIP-1α, MIP-1β and TNF-R1, displaying accuracy rates of 0.898, 0.987 and 1.0 between the anal fistula with chronic diarrhea and healthy control groups. Accuracy rates between the anal fistula with chronic diarrhea and the chronic diarrhea only groups were 0.9768, 0.909 and 0.964, respectively. Conclusions These results suggest the feasibility of employing serum proteins MIP-1α, MIP-1β and TNF-R1 as potential biomarkers for rapid and convenient diagnosis of anal fistula in chronic diarrhea patients.

To develop a nomogram based on pretreatment dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) to predict pathologic complete response (pCR) after neoadjuvant chemotherapy (NAC) in patients with triple-negative breast cancer (TNBC). A total of 108 female patients with TNBC treated with neoadjuvant chemotherapy followed by surgery between January 2017 and October 2020 were enrolled. The patients were randomly divided into the primary cohort (n = 87) and validation cohort (n = 21) at a ratio of 4:1. The pretreatment DCE-MRI and clinicopathological features were reviewed and recorded. Univariate analysis and multivariate logistic regression analyses were used to determine the independent predictors of pCR in the primary cohort. A nomogram was developed based on the predictors, and the predictive performance of the nomogram was evaluated by the area under the receiver operating characteristic (ROC) curve (AUC). The validation cohort was used to test the predictive model. Tumor volume measured on DCE-MRI, time to peak (TTP), and androgen receptor (AR) status were identified as independent predictors of pCR. The AUCs of the nomogram were 0.84 (95% CI: 0.75–0.93) and 0.79 (95% CI: 0.59–0.99) in the primary cohort and validation cohort, respectively. Pretreatment DCE-MRI could predict pCR after NAC in patients with TNBC. The nomogram can be used to predict the probability of pCR and may help individualize treatment. • Pretreatment DCE-MRI findings can predict pathologic complete response (pCR) after neoadjuvant chemotherapy in patients with triple-negative breast cancer. • A nomogram based on the independent predictors of tumor volume measured on DCE-MRI, time to peak, and androgen receptor status could help personalized cancer treatment in TNBC patients.

Objective Helicobacter pyloriinfection is mostly a family-based infectious disease. To facilitate its prevention and management, a national consensus meeting was held to review current evidence and propose strategies for population-wide and family-basedH. pyloriinfection control and management to reduce the related disease burden. Methods Fifty-seven experts from 41 major universities and institutions in 20 provinces/regions of mainland China were invited to review evidence and modify statements using Delphi process and grading of recommendations assessment, development and evaluation system. The consensus level was defined as ≥80% for agreement on the proposed statements. Results Experts discussed and modified the original 23 statements on family-basedH. pyloriinfection transmission, control and management, and reached consensus on 16 statements. The final report consists of three parts: (1)H. pyloriinfection and transmission among family members, (2) prevention and management ofH. pyloriinfection in children and elderly people within households, and (3) strategies for prevention and management ofH. pyloriinfection for family members. In addition to the ‘test-and-treat’ and ‘screen-and-treat’ strategies, this consensus also introduced a novel third ‘family-basedH. pyloriinfection control and management’ strategy to prevent its intrafamilial transmission and development of related diseases. Conclusion H. pyloriis transmissible from person to person, and among family members. A family-basedH. pyloriprevention and eradication strategy would be a suitable approach to prevent its intra-familial transmission and related diseases. The notion and practice would be beneficial not only for Chinese residents but also valuable as a reference for other highly infected areas.

Purpose This study reports data from the first evaluation of etelcalcetide treatment in Chinese adults with chronic kidney disease and secondary hyperparathyroidism. Methods This phase I, randomized study compared thrice-weekly etelcalcetide (5 mg per dose intravenously) and placebo in 33 Chinese adults (aged 18-70 years) receiving hemodialysis. Patients in both treatment groups received standard-of-care treatment with a total of 12 doses of the investigational product during a 4-week treatment period, followed by 4 weeks of washout and follow-up. Pharmacokinetic (PK) parameters (primary endpoint), tolerability (secondary endpoint), and changes in intact parathyroid hormone (iPTH) and corrected calcium (cCa) concentrations (exploratory endpoints) were assessed. PK parameters, ie, the maximum plasma concentration (Cmax) and area under the plasma concentration–time curve (AUC0–last), assessed over the interdialytic interval following the first and last doses were evaluated. The incidence of treatment-emergent adverse events (AEs) and anti-etelcalcetide antibodies was assessed. Findings Etelcalcetide administered to 25 patients was compared with placebo administered to 8 patients. Etelcalcetide exposure, assessed by Cmax and AUC0–last, increased after multiple-dose administration of etelcalcetide through day 27, with a mean (SD) accumulation ratio of 3.02 (0.61) based on AUC. At least one AE was reported for all patients in the etelcalcetide group and for 87.5% of patients in the placebo group. Serious AEs were reported in 12% of patients in the etelcalcetide group only. No deaths occurred, and a single discontinuation because of patient withdrawal of consent was reported in the etelcalcetide group. Preexisting anti-etelcalcetide antibodies were detected in one patient. The mean serum cCa level for all patients was maintained at >1.75 mmol/L. The iPTH and cCa concentrations decreased as expected, and a maximum mean decrease from baseline of 35.13% in iPTH levels was detected on day 27. Implications Multiple doses of 5 mg etelcalcetide were well tolerated, and observed etelcalcetide PK and safety profiles were similar to those in reports in adults of ethnicities other than Chinese. Changes in serum iPTH and serum calcium levels were consistent with expected responses to etelcalcetide. ClinicalTrials.gov identifier: NCT03283098.

Objective: A cardinal feature of Marfan syndrome is thoracic aortic aneurysm. The contribution of the renin-angiotensin system via AT1aR (Ang II [angiotensin II] receptor type 1a) to thoracic aortic aneurysm progression remains controversial because the beneficial effects of angiotensin receptor blockers have been ascribed to off-target effects. This study used genetic and pharmacological modes of attenuating angiotensin receptor and ligand, respectively, to determine their roles on thoracic aortic aneurysm in mice with fibrillin-1 haploinsufficiency ( Fbn1 C1041G/+ ). Approach and Results: Thoracic aortic aneurysm in Fbn1 C1041G/+ mice was found to be strikingly sexual dimorphic. Males displayed aortic dilation over 12 months while aortic dilation in Fbn1 C1041G/+ females did not differ significantly from wild-type mice. To determine the role of AT1aR, Fbn1 C1041G/+ mice that were either +/+ or −/− for AT1aR were generated. AT1aR deletion reduced expansion of ascending aorta and aortic root diameter from 1 to 12 months of age in males. Medial thickening and elastin fragmentation were attenuated. An antisense oligonucleotide against angiotensinogen was administered to male Fbn1 C1041G/+ mice to determine the effects of Ang II depletion. Antisense oligonucleotide against angiotensinogen administration attenuated dilation of the ascending aorta and aortic root and reduced extracellular remodeling. Aortic transcriptome analyses identified potential targets by which inhibition of the renin-angiotensin system reduced aortic dilation in Fbn1 C1041G/+ mice. Conclusions: Deletion of AT1aR or inhibition of Ang II production exerted similar effects in attenuating pathologies in the proximal thoracic aorta of male Fbn1 C1041G/+ mice. Inhibition of the renin-angiotensin system attenuated dysregulation of genes within the aorta related to pathology of Fbn1 C1041G/+ mice.

BACKGROUND Congenital coronary artery fistula can lead to symptoms of chest tightness, chest pain, or exertional dyspnea, which is a congenital vascular malformation that should not be ignored. Patients who have such malformations are frequently observed with different concurrent abnormal anatomic structures. Collateral circulation may have a positive effect on improving the patients' symptoms. CASE SUMMARY A 53-year-old female experienced episodic chest discomfort for the past month with symptoms manifesting when she was agitated or overexerted. After a positive treadmill test, the patient underwent coronary angiography. “Ghostlike” intermittent appearance of coronary ventricular fistula and collateral branching were observed. The patient was diagnosed with a right coronary ventricular fistula and collateral circulation. CONCLUSION This case shows the likelihood of collateral circulation in patients with coronary artery fistula. This may provide medical staff with novel solutions to treat insufficiency of myocardial blood supply induced by cardiovascular malformations.

Li-Hong Lu, Yu-Qing Song, Qi-Ming Wu, Zhao Wang, Yong-Fu Chen, Qian Dong, Xiao-Tao Han Department of Cardiology, Beijing Ditan Hospital, Capital Medical University, Beijing, 100015, People’s Republic of ChinaCorrespondence: Qi-Ming WuDepartment of Cardiology, Beijing Ditan Hospital, Capital Medical University, No. 8 of Jingshun Street, Chaoyang District, Beijing, 100015, People’s Republic of ChinaTel +86 138 0100 9058Fax +86 10-84322988Email lulihong1954@163.comObjective: To improve our knowledge of cardiac manifestations caused by brucellosis through analyzing abnormal electrocardiograms of patients infected with brucella.Methods: A total of 108 cases were enrolled, and their electrocardiograms were analyzed and summarized retrospectively.Results: Among 108 cases, 77 (71.3%) had a normal electrocardiogram, and 31 (28.7%) had an abnormal electrocardiogram. There were 13 cases with nodal tachycardia (12%), 9 cases with sinus bradycardia (8%), 7 cases with sinus arrhythmia (6%), 8 cases with left ventricular high voltage (7%), 13 cases with abnormal ST segment and T wave (12%), 2 cases with abnormal Q wave (1.85%), 3 cases with complete right bundle branch block (2.78%), 3 cases with ventricular premature beat (2.78%), 1 case with left anterior fascicular block (0.9%), 1 case with first degree a-v block (0.9%), 1 case with QT internal prolongation (0.9%), 1 case with poor R wave progression (0.9%), and 1 case with short PR interval (0.9%).Conclusion: The cardiac manifestations of brucellosis were rare, but the mortality was high. Patients with abnormal electrocardiogram should have improved echocardiography in time. Early detection of the abnormal electrocardiogram could give a hint of cardiac damage to avoid the serious consequences.Keywords: brucella, brucellosis, ECG, manifestations, cardiac manifestations

Background Previous studies have demonstrated the preclinical pharmacological and toxicological consistency, and clinical pharmacokinetic equivalence of bevacizumab biosimilar LY01008 with reference bevacizumab (Avastin). This randomized controlled trial aimed to compare the efficacy and safety of LY01008 with Avastin in first‐line treatment of Chinese patients with advanced or recurrent non‐squamous non‐small cell lung cancer (NSCLC). Methods Stage IIIB‐IV NSCLC patients with evaluable lesions, good physical status, and adequate organ functions from 67 centers across China were randomized in a ratio of 1:1 to receive LY01008 or Avastin 15 mg/kg intravenously in combination with paclitaxel/carboplatin (combined treatment) for 4‐6 cycles, followed by maintenance monotherapy with LY01008 until disease progression, intolerable toxicity, or death. The primary endpoint was objective response rate (ORR) in accordance with Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 confirmed by independent radiological review committees (IRRC). Secondary endpoints included disease control rate (DCR), duration of response (DoR), progression‐free survival (PFS), overall survival (OS), and safety. This study was registered in ClinicalTrials.gov (NCT03533127). Results Between December 15th, 2017, and May 15th, 2019, a total of 649 patients were randomized to the LY01008 (n = 324) or Avastin (n = 325) group. As of September 25th, 2019 for primary endpoint analysis, 589 patients received ORR evaluation, with a median number of combined treatment cycles of 5 (range 1‐6) and median duration of treatment of 3.0 (range 0.0‐5.1) months. ORR of response‐evaluable patients in the LY01008 and Avastin groups were 48.5% and 53.0%, respectively. The stratified ORR ratio was 0.91 (90% CI 0.80‐1.04, within the prespecified equivalence margin of 0.75‐1.33). Up to May 15th, 2020, with a median follow‐up of 13.6 (range 0.8‐28.4) months, no notable differences in DCR, median DoR, median PFS, median OS, and 1‐year OS rate were observed between the LY01008 and Avastin groups. There were no clinically meaningful differences in safety and immunogenicity across treatment groups. Conclusions LY01008 demonstrated similarity to Avastin in terms of efficacy and safety in Chinese patients with advanced or recurrent non‐squamous NSCLC. LY01008 combined with paclitaxel/carboplatin is expected to become a new treatment option for unresectable, metastatic, or recurrent non‐squamous NSCLC patients in the first‐line setting., This study demonstrated similarity between LY01008 and reference bevacizumab (Avastin) in terms of efficacy, safety, and immunogenicity in combination with paclitaxel and carboplatin as first‐line treatment in Chinese patients with advanced non‐squamous NSCLC.

Rationale: The renin-angiotensin system is a complex regulatory network that maintains normal physiological functions. The role of the renin-angiotensin system in sepsis-induced myocardial dysfunction (SIMD) is poorly defined. AGT (Angiotensinogen) is the unique precursor of the renin-angiotensin system and gives rise to all angiotensin peptides. The effects and mechanisms of AGT in the development of SIMD have not been defined. Objective: To determine a role of AGT in SIMD and investigate the underlying mechanisms. Methods and Results: Either intraperitoneal injection of lipopolysaccharide or cecal ligation and puncture significantly enhanced AGT abundances in liver, heart, and plasma. Deficiency of hepatocyte-derived AGT, rather than cardiomyocyte-derived AGT, alleviated septic cardiac dysfunction in mice and prolonged survival time. Further investigations revealed that the effects of hepatocyte-derived AGT on SIMD were partially associated with augmented Ang II (angiotensin II) production in circulation. In addition, hepatocyte-derived AGT was internalized by LRP1 (LDL [low-density lipoprotein] receptor-related protein 1) in cardiac fibroblasts and subsequently activated NLRP3 (NLR family pyrin domain-containing 3) inflammasome via an Ang II–independent pathway, ultimately promoting SIMD by suppressing SERCA2a (sarco[endo]plasmic reticulum Ca[2+]-ATPase 2a) abundances in cardiomyocytes. Conclusions: Hepatocyte-derived AGT promoted SIMD via both Ang II–dependent and Ang II–independent pathways. We identified a liver-heart axis by which AGT regulated development of SIMD. Our study may provide a potential novel therapeutic target for SIMD.

Objectives After ischemic stroke, microglia will be activated and play a key role in neuroinflammation and the destruction of the blood-brain barrier (BBB), and activated microglia could polarize into pro-inflammation M1 phenotype and anti-inflammation M2 phenotype. Dimethyl malonate (DMM) could reduce reactive oxygen species and we speculate DMM could regulate microglia to protect ischemic brain. Methods We used transient middle cerebral artery occlusion (tMCAO) mouse model to simulate ischemic stroke and adult male C57BL/6 mice were used in our study. 2,3,5-triphenyltetrazolium chloride staining was used to measure infarct volume. Evans Blue and Brain water content were used to evaluate the destruction of BBB. We used a five-point scale to assess the neurologic function of mice. Western blot and Immunofluorescence were used to measure microglia, pericytes and the expression of related proteins. Results DMM reduced cerebral infarct volume, Evans blue leakage, brain water content and improved neurologic deficits after tMCAO. The number of activated microglia and M1 microglia were decreased and the number of M2 microglia and pericytes were increased after DMM treatment. The expression of tumor necrosis factor-α was reduced while protein levels of IL-10 and ZO-1 were increased through DMM treatment. Conclusions DMM could regulate activation and polarization of microglia to inhibit neuroinflammation and protect BBB.

Objectives To demonstrate the challenges of interpreting cross-country comparisons of paediatric asthma hospital admission rates as an indicator of primary care quality. Methods We used hospital administrative data from >10 million children aged 6–15 years, resident in Austria, England, Finland, Iceland, Ontario (Canada), Sweden or Victoria (Australia) between 2008 and 2015. Asthma hospital admission and emergency department (ED) attendance rates were compared between countries using Poisson regression models, adjusted for age and sex. Results Hospital admission rates for asthma per 1000 child-years varied eight-fold across jurisdictions. Admission rates were 3.5 times higher when admissions with asthma recorded as any diagnosis were considered, compared with admissions with asthma as the primary diagnosis. Iceland had the lowest asthma admission rates; however, when ED attendance rates were considered, Sweden had the lowest rate of asthma hospital contacts. Conclusions The large variations in childhood hospital admission rates for asthma based on the whole child population reflect differing definitions, admission thresholds and underlying disease prevalence rather than primary care quality. Asthma hospital admissions among children diagnosed with asthma is a more meaningful indicator for inter-country comparisons of primary care quality.

Microvascular invasion (MVI) affects recurrence after treatment of small hepatocellular carcinoma (sHCC) of ≤3 cm in size. The present study aimed to investigate whether abdominal subcutaneous adipose tissue (SAT), visceral adipose tissue (VAT), and intermuscular adipose tissue (IMAT) are associated with MVI in patients with sHCC.A total of 124 patients with pathologically-confirmed sHCC diagnosed on surgical resection at the First Hospital Affiliated to Army Military University were recruited and divided into two groups according to MVI classification criteria (i.e., MVI-positive or MVI-negative). The SAT, VAT, and IMAT areas at the lumbar 3 vertebral level were imaged with abdominal computed tomography and measured using ImageJ software. Their association with MVI in sHCC was analyzed.Of the 124 patients with sHCC, 67 were MVI-positive and 57 were MVI-negative. Univariate analysis revealed a significant difference in the abdominal VAT and SAT between the MVI-positive and MVI-negative groups (The results of this study suggest that the areas of abdominal SAT and VAT are of significant clinical value because they can effectively predict the MVI status in patients with sHCC.

Background To identify the association between diabetes mellitus (DM) and the risk of chemotherapy-induced peripheral neuropathy (CIPN) through a systematic review and meta-analysis. Methods An electronic literature search was conducted in PubMed, Embase, Web of Science, the Wanfang database, the VIP Journals database (CQVIP), the China National Knowledge Infrastructure (CNKI) database, and the China Biology Medicine database (Sinomed) between January 2010 and January 2021. Articles were included if they investigated CIPN and DM. Stata 15.1 was used to analyze the data. Results We examined 8923 cancer patients from 25 studies comprising 9 cohort studies and 16 case–control studies. Meta-analysis showed that there was a statistically significant positive correlation between DM and CIPN (odds ratio [OR] = 1.60, 95% confidence interval [CI] = 1.38–1.85, P P = 0.824) showed no evidence of publication bias. The positive associations did not significant differ by study type, study quality, evaluation instrument, and type of antineoplastic drug. Omission of any single study had little effect on the combined risk estimate. Little evidence of heterogeneity was observed. Conclusion This meta-analysis provides evidence of a significant positive association between DM and risk of CIPN. Furthermore, a more detailed evaluation is warranted for cancer patients with diabetes when they are treated with antineoplastic drugs that have the potential to cause peripheral neuropathy.

OBJECTIVES People living with HIV (PLWH) have a high risk of kidney injury. Measurement of serum creatinine, along with proteinuria, is not sensitive to detect early kidney injury. Here, we investigated novel urinary biomarkers of early renal injury in PLWH. METHODS We performed a cross-sectional study of 166 antiretroviral-naive PLWH and 99 HIV-negative persons who all had an estimated glomerular filtration rate > 90 mL/min/1.73 m2 . We compared the levels of seven urinary biomarkers between the two groups using the propensity score matching (PSM) approach and explored the risk factors associated with elevated urinary biomarkers in PLWH. RESULTS Eighty-three pairs were successfully matched based on PSM. Compared with the HIV-negative group, the HIV-positive group had higher ratios of N-acetyl-β-D-glucosaminidase (NAG) to urine creatinine (UCr), alpha1-microglobulin (α1-M) to UCr, kidney injury marker-1 (KIM-1) to UCr, neutrophil gelatinase-associated lipocalin to UCr, and epidermal growth factor to UCr, whereas the Tamm-Horsfall protein to UCr ratio and the abnormal albumin to UCr ratio were not significantly different. Positive correlations were observed between HIV RNA level and NAG: UCr (rs = 0.32; P

Introduction:. Scabies is an infectious skin disorder caused by the mite Sarcoptes scabiei. The diagnosis of scabies is often confirmed by microscopic detection of scabies mites, eggs, or feces. We herein describe the diagnosis of scabies in a boy with the assistance of dermoscopy and fluorescence microscopy. Case presentation:. A 16-year-old Chinese boy presented with a 2-month history of extensive papules and excoriations with intense pruritus on the trunk and limbs. Dermoscopy showed a sinuous burrow in the finger webs with a brown jet-shaped triangular structure at the end. A fluorescence microscopy revealed a hatching egg and a mite. The boy was diagnosed with scabies and treated with 5% sulfur ointment. Discussion:. The use of dermoscopy in patients with scabies reveals a sinuous burrow with a brown jet-shaped triangular structure composed of the pigmented head and anterior legs of the mite[1]. A fluorescence microscopy revealed mites and eggs with blue fluorescence after staining, allowing us to easily identify scabies. Conlcusion:. The combination of dermoscopy-guided tape testing with fluorescence staining technology may enhance the diagnostic accuracy and efficiency of scabies.

Lung cancer is the most common cancer and cause of cancer death in Canada, with approximately 50% of cases diagnosed at stage IV. Sociodemographic inequalities in lung cancer diagnosis have been documented, but it is not known if inequalities exist with respect to immigration status. We used multiple linked health-administrative databases to create a cohort of Ontarians 40–105 years of age who were diagnosed with an incident lung cancer between 1 April 2012 and 31 March 2017. We used modified Poisson regression with robust standard errors to examine the risk of diagnosis at late vs. early stage among immigrants compared to long-term residents. The fully adjusted model included age, sex, neighborhood-area income quintile, number of Aggregated Diagnosis Group (ADG) comorbidities, cancer type, number of prior primary care visits, and continuity of care. Approximately 62% of 38,788 people with an incident lung cancer from 2012 to 2017 were diagnosed at a late stage. Immigrants to the province were no more likely to have a late-stage diagnosis than long-term residents (63.5% vs. 62.0%, relative risk (RR): 1.01 (95% confidence interval (CI): 0.99–1.04), adjusted relative risk (ARR): 1.02 (95% CI: 0.99–1.05)). However, in fully adjusted models, people with more comorbidities were less likely to have a late-stage diagnosis (adjusted relative risk (ARR): 0.82 (95% CI: 0.80–0.84) for those with 10+ vs. 0–5 ADGs). Compared to adenocarcinoma, small cell carcinoma was more likely to be diagnosed at a late stage (ARR: 1.29, 95% CI: 1.27–1.31), and squamous cell (ARR: 0.89, 95% CI: 0.87–0.91) and other lung cancers (ARR: 0.93, 95% CI: 0.91–0.94) were more likely to be diagnosed at an early stage. Men were also slightly more likely to have late-stage diagnosis in the fully adjusted model (ARR: 1.08, 95% CI: 1.05–1.08). Lung cancer in Ontario is a high-fatality cancer that is frequently diagnosed at a late stage. Having fewer comorbidities and being diagnosed with small cell carcinoma was associated with a late-stage diagnosis. The former group may have less health system contact, and the latter group has the lung cancer type most closely associated with smoking. As lung cancer screening programs start to be implemented across Canada, targeted outreach to men and to smokers, increasing awareness about screening, and connecting every Canadian with primary care should be system priorities.

Background The assessment of retroperitoneal lymph node status in patients with locally advanced cervical cancer is still a problem. This study aimed to explore the choice of these assessment methods. Methods Laparoscopic retroperitoneal lymphadenectomy was performed in 96 patients with advanced cervical cancer. The positive rates of lymph node metastasis were analyzed. The values of computed tomography lymph node minimum axial diameter (MAD) and squamous cell carcinoma antigen (SCC-Ag), and their combination in predicting retroperitoneal lymph node metastasis were compared. High-risk factors for common iliac lymph node (CILN) and/or para-aortic lymph node (PALN) metastasis were analyzed. Results The lymph node metastasis rate was 62.50% and the CILN and/or PALN metastasis rate was 31.25%. Overall, 96 patients had 172 visible lymph nodes. The positive rate of lymph node metastasis was significantly higher in the MAD ≥1.0 cm group (83.33%) than in the 0.5 cm ≤ MAD Conclusion Patients with MAD ≥1.0 cm and SCC-Ag ≥ 5.2 ng/mL, as well as high risk factors for CILN and/or PALN metastasis, should undergo resection of enlarged lymph nodes below the common iliac gland and lymphadenectomy of CILN/PALN to reduce tumor burden and to clarify lymph node metastasis status for accurate guidance in follow-up treatment. Patients with MAD

Population‐level identification of children and youth with ASD is essential for surveillance and planning for required services. The objective of this study was to develop and validate an algorithm for the identification of children and youth with ASD using administrative health data. In this retrospective validation study, we linked an electronic medical record (EMR)‐based reference standard, consisting 10,000 individuals aged 1–24 years, including 112 confirmed ASD cases to Ontario administrative health data, for the testing of multiple case‐finding algorithms. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and corresponding 95% confidence intervals (CI) were calculated for each algorithm. The optimal algorithm was validated in three external cohorts representing family practice, education, and specialized clinical settings. The optimal algorithm included an ASD diagnostic code for a single hospital discharge or emergency department visit or outpatient surgery, or three ASD physician billing codes in 3 years. This algorithm's sensitivity was 50.0% (95%CI 40.7–88.7%), specificity 99.6% (99.4–99.7), PPV 56.6% (46.8–66.3), and NPV 99.4% (99.3–99.6). The results of this study illustrate limitations and need for cautious interpretation when using administrative health data alone for the identification of children and youth with ASD. Lay Summary We tested algorithms (set of rules) to identify young people with ASD using routinely collected administrative health data. Even the best algorithm misses more than half of those in Ontario with ASD. To understand this better, we tested how well the algorithm worked in different settings (family practice, education, and specialized clinics). The identification of individuals with ASD at a population level is essential for planning for support services and the allocation of resources. Autism Res 2021, 14: 1037–1045. © 2021 The Authors. Autism Research published by International Society for Autism Research published by Wiley Periodicals LLC.

Primary tumors of the spinal cord are rare, accounting for 3-6% of tumors in the central nervous system, particularly in children. KIAA1549-BRAF fusion is more common in pilocytic astrocytoma (PA) and IDH1 R132H mutation is rare in infratentorial tumors. Here, we report a 10-year-old male patient who presented with weakness in lower limbs that progressed to difficulty walking. Magnetic resonance imaging (MRI) revealed an intramedullary solid-cystic lesion from the medulla oblongata to the thoracic spin 4 level, with the expansion of the spinal cord. The lesion exhibited patchy enhancement at C4-T1, indicating a tentative diagnosis of astrocytoma. The patient underwent resection of the lesion in the spinal canal from the cervical 6 level to the thoracic 2 level. Histopathology confirmed diagnosis of astrocytoma, WHO grade 2. Genetic analysis showed both IDH1 R132H mutation and KIAA1549-BRAF fusion. Therefore, our integrated diagnosis was astrocytoma, IDH mutation, WHO grade 2. Its molecular analyses include IDH1 R132H mutation and KIAA1549-BRAF fusion. After the operation, the patient did not receive chemo- or radiotherapy, and underwent an aggressive rehabilitation regiment. Follow up 10 months later, symptoms improved. To our best knowledge, this is the first case of concomitant IDH mutation and BRAF fusion in pediatric spinal cord astrocytoma.

To evaluate the prevalence of Helicobacter pylori infection and risk factors and to serotype the strains in Wuwei, located in north-western China, which has a high incidence of gastric cancer.Helicobacter pylori infection was analysed in 21 291 adults byThe infection rate of H. pylori was 53.0%, and 90.1% of strains were type I strains. The H. pylori infection rate was higher among farmers (OR = 1.34, 95% CI: 1.19-1.50) and individuals who had a junior high school or higher education level (OR = 1.10, 95% CI: 1.06-1.15), and was lower in older individuals (OR = 0.86, 95% CI: 0.83-0.90), individuals with high income (OR = 0.93, 95% CI: 0.90-0.95), individuals with a habit of eating quickly (OR = 0.93, 95% CI: 0.87-0.99) and individuals who consumed more fruit and vegetables (OR = 0.90, 95% CI: 0.85-0.95). Individuals with history of cholecystitis/cholecystolithiasis, hypertension and asthma were negatively correlated with H. pylori infection (P 0.05).The prevalence of H. pylori infection is high in Wuwei. The major prevalent strain is type I strain. Age, education, occupation, household income, consumption of fruit and vegetables, and habit of eating quickly are independent risk factors for H. pylori infection, which is also associated with individuals with a history of extragastric diseases.Evaluer la prévalence de l'infection à Helicobacter pylori et les facteurs de risque et déterminer le sérotype des souches à Wuwei, situé dans le nord-ouest de la Chine, où l'incidence du cancer gastrique est élevée. MÉTHODES: L'infection à H. pylori a été analysée chez 21.291 adultes par un test respiratoire à l'urée auLa prévalence de l'infection à H. pylori est élevée à Wuwei. La principale souche répandue est du type I. L'âge, l'éducation, la profession, le revenu du ménage, la consommation de fruits et de légumes et l'habitude de manger rapidement sont des facteurs de risque indépendants d'infection à H. pylori, qui est également associée à des personnes ayant des antécédents de maladies extra-gastriques.

AIM: To investigate the clinical efficacy and safety of femtosecond laser-assisted steepest-meridian clear corneal incisions for correcting preexisting corneal astigmatism performed at the time of cataract surgery. METHODS: This prospective case series study comprised consecutive age-related cataract patients with corneal regular astigmatism (range: +0.75 to +2.50 D) who had femtosecond laser-assisted steepest-meridian clear corneal incisions (single or paired). Corneal astigmatism was performed with the Pentacam preoperatively and 3mo postoperatively. Total corneal astigmatism and steepest-meridian measured in the 3-mm central zone were used to guide the location, size and number of clear corneal incision. The vector analysis of astigmatic change was performed using the Alpins method. RESULTS: Totally 138 eyes of 138 patients were included. The mean preoperative corneal astigmatism was 1.31±0.41 D, and was significantly reduced to 0.69±0.34 D (equivalent to difference vector) after surgery (P

Aortic diameter is a standard parameter for defining disease severity of thoracic aortic aneurysms. In mouse studies, aortic diameters can be measured in situ directly, but this approach has a potential confounder of underestimation due to the absence of physiological arterial blood pressure. In the present study, we developed an in situ approach for authentic aortic measurements. Thoracic aortic aneurysms were induced by beta-aminopropionitrile (BAPN, 0.5% wt/vol) administration in 4-week-old male C57BL/6J mice. Ultrasonography was performed to examine aortic dimensions, and mice with thoracic aortic dilatations were terminated subsequently. After saline perfusion through the left ventricle, periaortic tissues were removed to expose thoracic aortas. Optimal cutting temperature (OCT) compound was injected via the left ventricle to maintain aortic patency. In situ aortic images were captured pre- and post-OCT injection. In mice with severe thoracic aortic aneurysms, smaller aortic diameters were observed prior to OCT injection compared to ultrasound measurements, while aortic diameters in situ after OCT were comparable to diameters measured using ultrasound. A telemetry system demonstrated that maximal luminal pressures during 150 ul of OCT injection were 90 mmHg. Immunostaining for CD31 revealed that endothelial cells were preserved in the intima after OCT injection. These results indicate that OCT injection does not cause aortic damages due to excess pressures. In conclusion, in situ imaging with OCT injection provides authentic aortic measurements without overt aortic damage in mice with thoracic aortic aneurysms.

Family study is an effective way to identify disease-causing mutations (DCMs) and characterize the clinical phenotype of genetic diseases. In this study we recruited a Chinese primary open-angle glaucoma (POAG) family spanning six generations and consisting 112 individuals, in which 63 were participated in. Targeted exome sequencing on the proband identified a heterozygous mutation (c.752T>C, p.Val251Ala) in MYOC gene. Sanger sequencing performed on all participants found that fourteen family members carried this mutation. Ten (71.4%) of them were diagnosed with POAG, two (14.3%) with ocular hypertension (OHT) and two (14.3%) without manifestations of glaucoma. According to the results of ophthalmic examinations of the family members and their medical history, we found that the Val251Ala mutation was associated with clinical phenotype including intermediate penetrance, high intraocular pressure (IOP), severe visual defects and requirement of surgery.

The spatial and temporal distribution of aquaporin-4 (AQP4) expression in rat brain following brain trauma and AQP4-siRNA treatment, as well as corresponding pathological changes, were studied to explore the mechanism underlying the effect of AQP4-siRNA treatment on traumatic brain injury (TBI). The rats in the sham operation group had normal structure, with AQP4 located in the perivascular end-foot membranes and astrocytic membranes in a polarized pattern. The accelerated polarity reversal was observed in the TBI group in 1–12 h after TBI. During this period, AQP4 abundance on the astrocytic membrane is gradually increased, while AQP4 abundance on the perivascular end-foot membrane declined rapidly. Twelve hours after TBI, AQP4 expression was depolarized, showing a shift from the perivascular end-foot membrane to the astrocytic membrane. Pathological observation showed that vasogenic edema occurred immediately after TBI, at which time the extracellular space was expanded, leading to severe intracellular edema. AQP4-siRNA reduced the polarity reversal index at the early stage of TBI recovery and reduced edema, demonstrating the potential benefit of reduced AQP4 expression during recovery from TBI.

Rationale and objectives Evaluate ability of radiological semantic traits assessed on multi-window computed tomography (CT) to predict lung cancer risk. Materials and methods A total of 199 participants were investigated, including 60 incident lung cancers and 139 benign positive controls. Twenty lung window features and 2 mediastinal window features were extracted and scored on a point scale in three screening rounds. Multivariate logistic regression analysis was used to explore the association of these radiological traits with the risk of developing lung cancer. The areas under the receiver operating characteristic curve (AUROC), sensitivity, specificity, and positive predictive value (PPV) were computed to evaluate the best predictive model. Results Combining mediastinal window-specific features with the lung window features-based model significantly improves performance compared to individual window features. Model performance is consistent both at baseline and the first follow-up scan, with an AUROC increased from 0.822 to 0.871 (p = 0.009) and from 0.877 to 0.917 (p = 0.008), respectively, for single to multi-window feature models. We also find that the multi-window CT based model showed better specificity and PPV, with PPV at the second follow-up scan improved to 0.953. Conclusion We find combining window semantic features improves model performance in identifying cancerous nodules. We also find that lung window features are more informative compared to mediastinal features in predicting malignancy.

Background: Ascending thoracic aortic aneurysm (ATAA) is caused by the progressive weakening and dilatation of the aortic wall and can lead to aortic dissection, rupture, and other life-threatening complications. To improve our understanding of ATAA pathogenesis, we aimed to comprehensively characterize the cellular composition of the ascending aortic wall and to identify molecular alterations in each cell population of human ATAA tissues. Methods: We performed single-cell RNA sequencing analysis of ascending aortic tissues from 11 study participants, including 8 patients with ATAA (4 women and 4 men) and 3 control subjects (2 women and 1 man). Cells extracted from aortic tissue were analyzed and categorized with single-cell RNA sequencing data to perform cluster identification. ATAA-related changes were then examined by comparing the proportions of each cell type and the gene expression profiles between ATAA and control tissues. We also examined which genes may be critical for ATAA by performing the integrative analysis of our single-cell RNA sequencing data with publicly available data from genome-wide association studies. Results: We identified 11 major cell types in human ascending aortic tissue; the high-resolution reclustering of these cells further divided them into 40 subtypes. Multiple subtypes were observed for smooth muscle cells, macrophages, and T lymphocytes, suggesting that these cells have multiple functional populations in the aortic wall. In general, ATAA tissues had fewer nonimmune cells and more immune cells, especially T lymphocytes, than control tissues did. Differential gene expression data suggested the presence of extensive mitochondrial dysfunction in ATAA tissues. In addition, integrative analysis of our single-cell RNA sequencing data with public genome-wide association study data and promoter capture Hi-C data suggested that the erythroblast transformation-specific related gene( ERG ) exerts an important role in maintaining normal aortic wall function. Conclusions: Our study provides a comprehensive evaluation of the cellular composition of the ascending aortic wall and reveals how the gene expression landscape is altered in human ATAA tissue. The information from this study makes important contributions to our understanding of ATAA formation and progression.

Background and aims Three to 10 minutes of smoking cessation advice by physicians is effective to increase quit rates, but is not routinely practised. We examined the effectiveness of physicians' very brief (approximately 30 sec) smoking cessation intervention on quit rates among Chinese outpatient smokers. Design A pragmatic, open-label, individually randomized controlled trial. Setting Seventy-two medical outpatient departments of hospitals and/or community health centers in Guangdong, China. Participants Chinese adults who were daily cigarette smokers (n = 13 671, 99% males) were invited by their physician to participate during outpatient consultation. Smokers who were receiving smoking cessation treatment or were judged to need specialist treatment for cessation were excluded. Interventions The intervention group (n = 7015) received a 30-sec intervention including physician's very brief advice, a leaflet with graphic warnings and a card with contact information of available cessation services. The control group (n = 6656) received a very brief intervention on consuming vegetables and fruit. A total of 3466 participants in the intervention group were further randomized to receive a brief booster advice from trained study personnel via telephone 1 month following their doctor visit. Measurements The primary outcome was self-reported 7-day point prevalence abstinence (PPA) in the intervention and control groups at the 12-month follow-up. Secondary outcomes included self-reported 30-day abstinence and biochemically validated abstinence at 12-month follow-up. Findings By intention-to-treat, the intervention (versus control) group had greater self-reported 7-day abstinence [9.1 versus 7.8%, odds ratio (OR) = 1.14, 95% confidence interval (CI) = 1.03-1.26, P = 0.008] and 30-day abstinence (8.0 versus 6.9%, OR = 1.14, 95% CI = 1.03-1.27, P = 0.01) at 12-month follow-up. The effect size increased when only participants who received the intervention from compliant physicians were included (7-day PPA, OR = 1.42, 95% CI = 1.11-1.74). The group difference in biochemically validated abstinence was small (0.8 versus 0.8%, OR = 1.00, 95% CI = 0.71-1.42, P = 0.99). Conclusion A 30-sec smoking cessation intervention increased self-reported abstinence among mainly male smokers in China at 12-month follow-up (risk difference = 1.3%), and should be feasible to provide in most settings and delivered by all health-care professionals.

To assess the effects of upright positions on maternal outcomes for women without epidural analgesia in comparison with recumbent positions during the second stage of labour.Upright positions have many physiological advantages. The underlying benefits and risks of upright positions during the second stage of labour have been reported in many studies but the results are divergent.A meta-analysis of randomized controlled trials.The Cochrane Library, PubMed, Embase, CINAHL and ProQuest databases were systematically searched from inception to 17 June 2019.We conducted the quality appraisal using the Cochrane Collaboration's tool and performed meta-analyses using the Review Manager 5.3 software. The primary outcomes were instrumental vaginal delivery and the duration of the second stage of labour.Overall, 12 studies including 4,314 women were included. Upright positions significantly decreased the rate of instrumental vaginal delivery (risk ratio [RR] = 0.74, 95% CI 0.59-0.93), shortened the active pushing phase (mean difference [MD] = -8.16 min, 95% CI -16.29 to -0.02), decreased the rate of severe perineal trauma (RR = 0.35, 95% CI 0.14-0.87) and episiotomy (RR = 0.52, 95% CI 0.29-0.92), but significantly increased the rate of second-degree perineal trauma (RR = 1.45, 95% CI 1.10-1.90). However, there was no significant difference in the duration of the second stage of labour or postpartum haemorrhage.Upright positions are beneficial for improving maternal outcomes. Several results should be considered with caution. Researchers need to clarify the definition of upright positions and conduct large, robust studies in the future to provide stronger evidence.This meta-analysis explores a crucial issue in intrapartum care and clarifies the benefits and possible risks of upright positions in the second stage of labour. Midwives and obstetricians are encouraged to apply upright positions depending on women's preferences and labour progress but should take measures to prevent perineal trauma.目的: 评估在第二产程中,与卧位相比,直立体位对未使用硬膜外镇痛的产妇的预后的影响。 背景: 从生理角度讲,直立体位具有许多优势。许多研究报告了第二产程期间直立体位的基本益处和风险,但结果却不尽相同。 设计: 随机对照试验的荟萃分析。 数据来源: 从各数据库成立至2019年6月17日,对Cochrane Library、PubMed、Embase、CINAHL和ProQuest等数据库进行了系统化检索。 审查方法: 使用科克伦协作网的工具进行质量评价,并使用Review Manager 5.3软件进行荟萃分析。主要预后指标是器械性阴道分娩和第二产程的持续时间。 结果: 总的来说,包括了12项研究,涉及4314名妇女。直立体位显著降低了器械性阴道分娩率(风险比[RR]=0.74,95%置信区间0.59-0.93),缩短了主动推宫阶段(平均差 [MD]=−8.16分钟, 95%置信区间−16.29 to −0.02),降低了严重会阴创伤发生率(RR=0.35, 95%置信区间0.14-0.87)和会阴切开术(RR=0.52, 95%置信区间0.29-0.92),但显著增加了二度会阴创伤的发生率(RR=1.45, 95%置信区间.10-1.90)。但在第二产程的持续时间或产后出血方面没有显著差异。 结论: 直立位有利于改善孕产妇预后。有几项结果应予以谨慎考虑。研究人员需要明确直立体位的定义,并在未来进行大规模、稳健的研究,以提供更有力的证据。 影响: 本荟萃分析探讨了产时护理中的一个关键问题,并阐明了直立体位在第二产程中的益处和可能存在的风险。鼓励助产士和产科医生根据产妇的喜好和产程进展采用直立体位,但应采取措施防止会阴创伤。.

Background/objectives Chronic kidney disease (CKD) is a global public health problem, including in China. The aim of this study was to identify the risk factors for the development and progression of subclinical renal disease (SRD) in a Chinese population. We also examined whether the impact of the risk factors on SRD changed over time. Subjects/methods To identify the predictors of SRD, we performed a cross-sectional study of the 2432 subjects in our Hanzhong Adolescent Hypertension Cohort. A subgroup of 202 subjects was further analyzed over a 12-year period from 2005 to 2017 to determine the risk factors for the development and progression of SRD. Results In cross-sectional analysis, elevated blood pressure, male gender, diabetes, body mass index, and triglyceride were independently associated with a higher risk of SRD. In longitudinal analysis, an increase in total cholesterol over a 4-year period and an increase in serum triglyceride over a 12-year period were independently associated with progression of albuminuria. Finally, increases in both total cholesterol and serum uric acid over a 4-year follow-up showed an independent association with a modest reduction in estimated glomerular filtration rate (eGFR). Conclusions In this study of a Chinese cohort, we show several metabolic abnormalities as independent risk factors for subclinical renal disease in a Chinese cohort. In addition, we demonstrate that the effects of total cholesterol, triglycerides and uric acid on the development and progression of albuminuria or the decline in eGFR vary at different points of follow-up. These findings highlight the importance of early detection of metabolic abnormalities to prevent SRD.

Amoxicillin and proton pump inhibitor dual Helicobacter pylori therapy has proved not to be reliably highly effective primarily because of traditional proton pump inhibitors' inability to maintain a high intragastric pH. Clarithromycin and proton pump inhibitor H. pylori dual therapy failed in part because clarithromycin resistance emerged during therapy causing treatment failures. The combination of amoxicillin, clarithromycin, and proton pump inhibitor was subsequently undermined by increasing clarithromycin resistance. Although vonoprazan appeared to restore the effectiveness of triple therapy, the improvement was almost entirely to improved effectiveness of amoxicillin dual therapy component and resulted in the majority (>85% currently in Japan) of those receiving vonoprazan-amoxicillin plus a second antibiotic (e.g. clarithromycin, metronidazole, fluoroquinolone, or rifabutin) receiving no benefit from the second antibiotic. The results in somewhere between 2800 and 5600 kg of unnecessary clarithromycin per one million H. pylori treatment courses per year in Japan. The only contribution of the second antibiotic is to increase global antimicrobial resistance. There are now sufficient data to prove that optimized vonoprazan-amoxicillin dual therapy can reliably achieve cure rates ≥95%. This manuscript discusses use of the principles of antimicrobial stewardship to develop potassium-competitive acid blocker-containing H. pylori therapies that will reliably achieve high H. pylori cure rates with minimal or no use of excess antibiotics. Such therapies are urgently needed so that use of vonoprazan triple therapies can be curtailed while also improving overall H. pylori cure rates.

Cartilaginous metaplasia is rare in primary central nervous system (CNS) neoplasms and has not been described in the histone 3 (H3) gene (H3) with a substitution of lysine to methionine (H3 K27M mutant) diffuse midline glioma before. Here, we report a case of H3 K27M mutant diffuse midline glioma with cartilaginous metaplasia in a 56-year-old woman. Magnetic resonance imaging (MRI) revealed a ring-enhanced lesion located in the medulla oblongata and extended superiorly into the fourth ventricle. The tumor was macroscopically completely resected. Histologically, the tumor was composed of a gliomatous component and a well-differentiated cartilaginous component. Microvascular proliferation and necrosis were noted. According to immunohistochemical staining, glial cells were diffusely and strongly positive for glial fibrillary acidic protein (GFAP), oligodendrocyte lineage transcription factor 2 (Olig2), H3 K27M, and S-100 protein but negative for H3K27me3. The chondrocytes also were positive for GFAP and S-100 protein. The H3 K27M mutation was confirmed by sequencing in both the gliomatous and cartilaginous components, suggesting a common origin from the same progenitor cells. Based on these findings, the tumor was diagnosed as a diffuse midline glioma with H3 K27M mutation with widespread cartilaginous metaplasia, corresponding to WHO grade IV. This is an extremely rare H3 K27M mutant diffuse midline glioma with cartilaginous metaplasia, and reporting this unusual case adds to the understanding of this tumor type.

OBJECTIVE To screen for the presence of biomarkers involved in tubular injury and kidney damage in children with urolithiasis (RS), and to validate these proteins by ELISA. METHODS Prospective-controlled pilot study of children with urolithiasis and their age- and gender-matched controls (HC). Initial screening test was done by quantitative proteomic comparison of pooled urine from RS versus HC, using liquid chromatography-mass spectrometry. Proteins of interest were selected using the following criteria: (1) ≥5 spectral counts; (2) ≥2-fold difference in spectral counts; and (3) ≤.05 P value for the Fisher's Exact Test. Validation was performed by ELISA testing. Statistical analysis was performed by Student t-test and Mann-Whitney U test. RESULTS Proteomic analysis identified 3 proteins of interest, Cystatin C (CYTC), neutrophil gelatinase-associated lipocalin (NGAL) and lysozyme C that were significantly over-represented in RS group versus HC. ELISA analysis revealed significantly increased urinary levels of CYTC and NGAL, and nearly significantly increased urinary levels of lysozyme C in RS group (N = 24) compared to controls (N = 13). Subgroup analysis showed significantly higher urinary levels of CYTC in both hypercalciuria (N = 14) and hypocitraturia (N = 10) versus HC (P CONCLUSION Children with urolithiasis showed significant increase in urinary CYTC and NGAL irrespective of their normal serum creatinine. These biomarkers indicate tubular injury and early kidney damage and represent valid tools for early screening when traditional tests are normal.

Background Small nucleolar RNA host gene (SNHG) family members are newly recognized lncRNAs, which have been revealed to be oncogenes in several cancers. However, little studies investigated the expression and clinical implications of SNHGs in AML. Methods Herein, we systemically determined the prognostic role of the expression of SNHG family members in acute myeloid leukemia (AML). Results Among the expression of all SNHG family members, we identified that only SNHG7 and SNHG12 expression were found to have prognostic effects on overall survival (OS) and leukemia-free survival (LFS) in AML by Cox regression univariate analysis. Furthermore, Kaplan-Meier analysis showed that SNHG7 higher-expressed cases had markedly longer OS and LFS time than SNHG7 lower-expressed cases, whereas SNHG12 higher-expressed cases had markedly shorter OS and LFS time than SNHG12 lower-expressed cases. Interestingly, SNHG7 and SNHG12 expression were also associated with several prognosis-related clinical/molecular features such as white blood cell counts, FAB/cytogenetic classifications, IDH1 mutation, RUNX1 mutation, and NPM1 mutation. Despite the associations, Cox regression multivariate analysis confirmed the independent prognostic impact of SNHG7 and SNHG12 expression in AML. Notably, we further validated that both SNHG7 and SNHG12 expression was significantly increased in newly diagnosed AML patients. Conclusion Our findings demonstrated that SNHG7 and SNHG12 expression act as independent prognostic indicators in AML.

Thoracic aortic dissection (TAD) is one of the most lethal aortic diseases due to its acute onset, rapid progress, and high rate of aortic rupture. The pathogenesis of TAD is not completely understood. In this mini-review, we introduce three emerging experimental mouse TAD models using β-aminopropionitrile (BAPN) alone, BAPN for a prolonged duration (four weeks) and then with added infusion of angiotensin II (AngII), or co-administration of BAPN and AngII chronically. We aim to provide insights into appropriate application of these three mouse models, thereby enhancing the understanding of the molecular mechanisms of TAD.

High metabolic tumor volume (MTV) predicts worse outcomes in lymphoma treated with chemotherapy. However, it is unknown if this holds for patients treated with axicabtagene ciloleucel (axi-cel), an anti-CD19 targeted chimeric antigen receptor T-cell therapy. The primary objective of this retrospective study was to investigate the relationship between MTV and survival (overall survival [OS] and progression-free survival [PFS]) in patients with relapsed/refractory large B-cell lymphoma (LBCL) treated with axi-cel. Secondary objectives included finding the association of MTV with response rates and toxicity. The MTV values on baseline positron emission tomography of 96 patients were calculated via manual methodology using commercial software. Based on a median MTV cutoff value of 147.5 mL in the first cohort (n = 48), patients were divided into high and low MTV groups. Median follow-up for survivors was 24.98 months (range, 10.59-51.02 months). Patients with low MTV had significantly superior OS (hazard ratio [HR], 0.25; 95% confidence interval [CI], 0.10-0.66) and PFS (HR, 0.40; 95% CI, 0.18-0.89). Results were successfully validated in a second cohort of 48 patients with a median follow-up for survivors of 12.03 months (range, 0.89-25.74 months). Patients with low MTV were found to have superior OS (HR, 0.14; 95% CI, 0.05-0.42) and PFS (HR, 0.29; 95% CI, 0.12-0.69). In conclusion, baseline MTV is associated with OS and PFS in axi-cel recipients with LBCL.

Aims and objectives To assess the effects of flexible sacrum positions on mode of delivery, duration of the second stage of labour, perineal trauma, postpartum haemorrhage, maternal pain, abnormal foetal heart rate patterns and Apgar scores based on published literature. Background Maternal positions served as a nonmedical intervention may facilitate optimal maternal and neonatal outcomes during labour. Flexible sacrum positions are conducive to expanding pelvic outlet. Whether flexible sacrum positions have positive effects on maternal and neonatal well-being is a controversial issue under heated discussion. Design We performed a systematic review and meta-analysis based on PRISMA guidelines. Methods Randomised controlled trials (RCTs) comparing any flexible sacrum position with non-flexible sacrum position in the second stage of labour were included. PubMed, EMBASE, Cochrane Library, CINAHL, CNKI (China National Knowledge Infrastructure), SinoMed and Wanfang databases were searched from inception to 11 March 2019 for published RCTs. Risk of bias was assessed by the Cochrane criteria, and random-effects meta-analyses were conducted by RevMan 5.3. Results Sixteen studies (3,397 women) published in English were included. Flexible sacrum positions in the second stage of labour could reduce the incidence of operative delivery, instrumental vaginal delivery, caesarean section, episiotomy, severe perineal trauma, severe pain and shorten the duration of active pushing phase in the second stage of labour. However, flexible sacrum positions may increase the incidence of mild perineal trauma. There was no significant difference in the duration of the second stage of labour, maternal satisfaction and other outcomes. Conclusions Flexible sacrum positions are superior in promoting maternal well-being during childbirth. However, several results require careful interpretation. More rigorous original studies are needed to further explore their effects. Relevance to clinical practice The results support the use of flexible sacrum positions. Flexible sacrum positions are recommended to apply flexibly or tailor to individual woman's labour progress.

Background and objective: As a result of the pandemic, family physicians face the additional challenge of navigating COVID-19. The aim of this study was to provide simulated training for best-practice management of COVID-19 presentations for residency program trainees in Shanghai, China. Methods: A simulated suspected COVID-19 case was designed on the basis of a real patient. The simulation included: pre-and post-simulation surveys, a PowerPoint presentation, simulation practice, debriefing and reflection. Improvement in survey outcomes was assessed using a paired t-test. Results: A total of 25 trainees participated in the simulation, consisting of first-, second-and third-year family medicine residents. Significant improvement was observed in their knowledge of COVID-19, and sub-analysis showed that all three grades of residents improved their knowledge significantly. Ninety-six per cent of participants believed the simulation was very helpful. Discussion: The simulation scenario improves crisis management skills for family physicians managing the high risk of transmission of respiratory infectious diseases. Higher-order learning outcomes will be explored in future training programs.

Objective: To study the interaction effects of rs10757278 polymorphisms at 9p21 locus and traditional risk factors on coronary heart disease (CHD) in Xinjiang, China. Methods: This case–control study consecutively enrolled 310 unrelated consecutive CHD patients aged 18–70 years old. All study participants were recruited between January and December 2017 from The Heart Center of The First Affiliated Hospital of Xinjiang Medical University. CHD patients were confirmed by coronary angiography (≥50% diameter stenosis in at least one of the major coronary arteries) according to the American Heart Association criteria for the confirmation of CHD. Healthy subjects were randomly selected from the occupational population, who received physical examination in our hospital and matched to cases on the basis of age (±3 years) and sex, those without medical history of cardiovascular diseases, and 536 subjects were selected as the control group after medical history inquiry, physical examination, cardiac ultrasound, electrocardiogram, and other blood biochemical examinations in the hospital. The occupational stress was evaluated by an effort-reward imbalance questionnaire. An epidemiological survey was conducted to collect clinical data. Chi-squared test, analysis of variance, and binary logistic regression analysis were adopted. Results: Both the case and the control groups showed significant difference in smoking, drinking, physical activity, hypertension, diabetes mellitus, family history of CHD, and body mass index (BMI) (all P < 0.05); prevalence of CHD was not related to occupational stress. There was no significant difference in occupational stress level between the 2 groups (P > 0.05); Differences in rs10757278 genotype between the case group and the control groups were statistically significant; binary logistic regression analysis was used to evaluate the risk factors of CHD. After adjustment for age and sex, significant increased risk effects for CHD were found to be associated with smoking [odds ratio (OR) = 2.311; 95% confidence interval (CI): 1.04–2.499; P < 0.001], physical exercise (OR = 1.365; 95% CI: 1.137–1.639; P < 0.001), hypertension (OR = 4.627; 95% CI: 2.165–10.764; P < 0.001), family history of CHD (OR = 4.103; 95% CI: 3.169–6.892; P < 0.001), BMI (OR = 2.484; 95% CI: 2.036–3.03; P < 0.001), and GG genotype at rs10757278 (OR = 1.978; 95% CI: 1.413–2.769; P < 0.001); We noted that a significant interaction association between GG genotype at rs10757278 and CHD differs across categories of smoking, hypertension, family history of CHD, and BMI. Conclusion: GG genotype at rs10757278 may be a risk factor for CHD. And there are interaction effects between GG genotype of rs10757278 in region 9p21 gene and traditional risk factors.

BACKGROUND: Angiotensin (Ang)I is cleaved by angiotensin-converting enzyme (ACE) to generate AngII. The purpose of this study was to determine the roles of ACE in endothelial and smooth muscle cells in aortic aneurysms. METHODS AND RESULTS: AngI infusion led to thoracic and abdominal aortic aneurysms in low-density lipoprotein receptor-deficient mice, which were ablated by ACE inhibition. Endothelial or smooth muscle cell-specific ACE deletion resulted in reduction of AngI-induced thoracic, but not abdominal, aortic dilatation. CONCLUSIONS: AngI infusion causes thoracic and abdominal aortic aneurysms in mice. ACE in aortic resident cells has differential effects on AngI-induced thoracic and abdominal aortic aneurysms.

Alcoholism is a risk factor for the development of cognitive decline and dementia. Here we demonstrated that the glymphatic function in the brain was impaired by alcohol administration. Acute moderate alcohol administration substantially retarded and reduced the entry of subarachnoid cerebrospinal fluid (CSF) via the paravascular space into the cerebral parenchyma, thus impaired CSF-interstitial fluid (ISF) exchange and parenchymal amyloid β (Aβ) peptide clearance. The elevated release of β-endorphin and reduced cerebrovascular pulsatility after acute alcohol administration may account for the impairment of the glymphatic function. Chronic moderate alcohol consumption led to pronounced activation of astrocytes and a widespread loss of perivascular AQP4 polarization in the brain, which results in an irreversible impairment of the glymphatic function. The results of the study suggest that impaired glymphatic functions and reduced parenchymal Aβ clearance found in both acute and chronic alcohol treatment may contribute to the development of cognitive decline and dementia in alcoholism.

Background The complete blood count (CBC) is a basic test routinely ordered by physicians as a part of initial diagnostic work-up on their patients. To ensure safe clinical application of the CBC, reliable biological variation (BV) data are needed to establish analytical performance specifications. Our aim was to define the BV of CBC parameters using a rigorous protocol that is compliant with the Biological Variation Data Critical Appraisal Checklist (BIVAC) provided by the European Federation of Clinical Chemistry and Laboratory Medicine. Methods Blood samples drawn from 41 healthy Chinese subjects (22 females and 19 males; 23–59 years of age) once monthly for 6 consecutive months were analyzed using an ABX Pentra 80 instrument. The instrument was precisely calibrated. All samples were analyzed in duplicate for 13 CBC parameters. The data were assessed for outliers, normality, and variance homogeneity prior to nested ANOVA. Gender-stratified within-subject (CVI) and between-subject (CVG) BV estimates were calculated. Results The number of remaining data for each subject was 442–484 after removing outliers. No significant differences existed between female/male CVI estimates. Except for leukocytes, neutrophils, and lymphocytes, the mean values of 10 parameters differed significantly between genders, rendering partitioning of CVG data between genders. No significant differences were detected between most BV estimates and recently published estimates representing a Europid population. Conclusions Most BV estimates in BIVAC-compliant studies are similar. The turnover time of blood cells and age distribution of participants should be considered in a CBC BV study. Our study will contribute to global BV estimates and future studies.

Background Clinical practice guidelines on uncomplicated birth provide clinical practice guidance and help to reduce unnecessary, non-evidence-based and potentially harmful intrapartum care practices. Little is known about the trustworthiness and consistency of these guidelines. Objectives To appraise guidelines relevant to uncomplicated birth, and summarise consensus and non-consensus recommendations. Search strategy Eight literature databases and the websites of guideline development institutions and organisations of obstetricians, gynaecologists and midwives were searched from January 2008 to October 2018. Selection criteria Guidelines that: reported in Chinese or English; labelled guideline, or recommendation, or consensus, or practice parameter, or position paper/stand; with uncomplicated birth being the primary objectives or comprised chapter(s); and were the most recently published or updated versions. Data collection and analysis Two reviewers independently assessed guideline quality using the AGREE II instrument, and synthesised consensus and non-consensus recommendations using the content analysis approach. Main results Eleven guidelines met the inclusion criteria. The WHO and NICE guidelines were deemed to have the highest methodological quality. Twenty-three discrepant recommendations and 39 groups of unanimous recommendations (containing 113 individual ones) were identified, among which 14 recommendations including eating and drinking as desired, prophylactic uterotonics, routine amniotomy and episiotomy were included in five or more guidelines. Perineal massage, uterine massage, active or expectant management at the third stage and use of hands-on or hands-poised technique were identified as the main discrepant recommendations. Conclusions Two guidelines with higher methodological quality and key clinical guideline recommendations, including both consensus and non-consensus ones, on uncomplicated birth were identified. Tweetable abstract Clinical guidelines of uncomplicated birth agree and disagree on several key recommendations.

To identify the relationship between human epidermal growth factor receptor 2 (HER2) status and cone-beam breast CT (CBBCT) characteristics in surgically resected breast cancer. Preoperative CBBCT of patients with BI-RADS 4 or 5 lesions identified on mammography or ultrasound and dense or very dense breast tissue were retrospectively evaluated in 181 surgically resected breast cancer (triple-negative excluded) between May 2012 and November 2014. A set of CBBCT descriptors was semiquantitatively assessed by consensus double reading. Reader reproducibility was analyzed. Multivariable logistic regression analysis using backward elimination (BEA) with the Wald criterion was performed to identify independent predictive factors of harboring HER2/neu. Principle component analysis (PCA) was used to determine characteristics that might differentiate HER2 status. Receiver operating characteristic (ROC) curve analyses were conducted to determine the predictive capability. HER2 positive was found in 101 (55.8%) of 181 patients. Inter-observer agreement was high for characteristics’ assessment. Based on BEA, pathologic grade, maximum dimension, lobulation, ΔCT, and calcification morphology were confirmed as independent predictive factors of HER2/neu overexpression. PCA showed that calcification- and border-related characteristics were the most important for differentiation. ROC curve analyses showed that CBBCT features (AUC = 0.853) were superior to clinicopathologic features (AUC = 0.613, p

Background Gastric cancer (GC) is one of the leading causes of cancer-related death worldwide. This study was designed to investigate the prognostic values of red blood cell (RBC)-associated indicators, including RBC, hemoglobin (HGB), hematocrit (HCT), mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC), and RBC distribution width (RDW) in resectable GC patients. Methods In this retrospective study, a total of 104 pathologically confirmed GC patients were recruited. These cases were divided into two groups according to the median values of pretreatment RBC, HGB, HCT, MCV, MCH, MCHC, or RDW. To evaluate the changes in RBC-associated indicators values after treatment, we introduced the concept of post-/pre-treatment ratios (≤1 suggested RBC, HGB, HCT, MCV, MCH, MCHC, or RDW values were not increased after therapy, while >1 represented those in increased levels). Results The lower pretreatment MCHC levels were correlated with worse overall survival (OS), while pretreatment levels of RBC, HGB, HCT, MCV, MCH, or RDW were not. The whole course of treatment (surgery plus adjuvant chemotherapy) significantly decreased the values of MCHC, and increased the values of MCV and RDW, whereas it had no obvious effects on the values of RBC, HGB, HCT, or MCH. Patients with post-/pre-treatment MCV ratio >1 had an increased survival ratio. Meanwhile, post-/pre-treatment RBC, HGB, HCT, MCH, MCHC, or RDW ratios were not correlated with outcomes. Multivariate Cox regression analysis revealed that the American Joint Committee on Cancer (AJCC) stage (III), and lower pretreatment MCHC levels were independent risk factors affecting OS. The receiver operating characteristic (ROC) curve analysis showed that an MCHC value of 341.98 g/L was the optimal cutoff value for prognosis, with a sensitivity of 58.3% and a specificity of 75.0%. Conclusions Pretreatment MCHC levels could become a potential prognostic factor for resectable GC.

With the improvements of sanitation and nationwide safe water supply the occurrence of bacterial diarrhea declined remarkably, while viruses became the leading causes of acute gastroenteritis (AGE). Of these viruses, noroviruses (NoVs) are responsible for a considerable burden of gastroenteritis, especially in children < 2 years and elderly ⩾ 65 years. NoVs circulating in the Chinese population are antigenically highly diverse with the genotype GII.4 being the dominant strain followed by GII.3. Given the widespread contamination in environmental sources, and highly infectious nature of NoVs, vaccination would be the desirable strategy for the control of NoV infections. However, a better understanding of acquired immunity after infection, and a reliable immunological surrogate marker are urgently needed, since two vaccine candidates based on virus-like particles (VLPs) are currently moving into clinical evaluations in China.

PurposeThe controlling nutritional status (CONUT) score is a nutritional indicator that serves as a prognostic factor for many malignancies. This study aimed to investigate the prognostic significance of pre-treatment CONUT scores in patients with epithelial ovarian cancer.MethodsWe evaluated newly diagnosed patients with epithelial ovarian cancer who were treated at the Nantong Tumor Hospital, between January 2013 and April 2016. Pre-treatment CONUT scores were calculated using serum albumin levels, total lymphocyte counts, and cholesterol levels. The optimal CONUT score cut-off was determined via receiver operating characteristic curve and Youden’s index. The difference in survival rates between the high-CONUT score group and the low-CONUT score group was analyzed using Kaplan-Meier curves and the log-rank test. Univariate and multivariate Cox proportional hazard regression models were used to identify prognostic factors influencing survival in these patients.ResultsIn total, 206 patients were included. The optimal cut-off value for the CONUT score was 3. The high-CONUT score group (score ≥3) had higher International Federation of Gynecology and Obstetrics (FIGO) stages, medium-large amounts of ascitic fluid, higher CA125 levels, and more chemoresistance than those with a low-CONUT score (score ConclusionsThe CONUT score predicts the prognosis of epithelial ovarian cancer and is thus helpful for individualizing treatment and improving survival in these patients.

Chronic alcohol consumption dose-dependently affects the incidence and prognosis of ischemic stroke. We determined the influence of chronic alcohol consumption on cerebral angiogenesis under physiological conditions and following ischemic stroke. In in vitro studies, acute exposure to low-concentration ethanol significantly increased angiogenic capability and upregulated vascular endothelial growth factor A (VEGF-A) and vascular endothelial growth factor receptor 2 (VEGFR2) in C57BL/6J mouse brain microvascular endothelial cells (MBMVECs). The increased angiogenic capability was abolished in the presence of a VEGFR2 inhibitor. In addition, the increased angiogenic capability and upregulated VEGF-A and VEGFR2 remained in chronically low-concentration ethanol-exposed MBMVECs. In in vivo studies, 8-week gavage feeding with low-dose ethanol significantly increased vessel density and vessel branches and upregulated VEGF-A and VEGFR2 in the cerebral cortex under physiological conditions. Furthermore, vessel density, vessel branches, and expression of VEGF-A and VEGFR2 in the peri-infarct cortex were significantly greater in low-dose ethanol-fed mice at 72 h of reperfusion. Although low-dose ethanol did not alter cerebral vasoreactivity and regional cerebral blood flow (rCBF) either before or during ischemia, it significantly augmented post-ischemic hyperemia during reperfusion. In contrast, exposure to high-concentration ethanol and 8-week gavage feeding with high-dose ethanol only had a mild inhibitory effect on angiogenic capability and cerebral angiogenesis, respectively. We conclude that heavy alcohol consumption may not dramatically alter cerebral angiogenesis, whereas light alcohol consumption significantly promotes cerebral angiogenesis.

Background Dyspepsia is a common cause of physician visits. If and when endoscopy should be performed depend on the regions and the populations. This study aimed to identify the current risk factors predictive of upper gastrointestinal malignancy or peptic ulcer in China with high prevalence of gastric cancer. Methods A questionnaire was conducted among consecutive outpatients undergoing their first esophagogastroduodenoscopy for dyspepsia. Symptoms other than alarm symptoms in this study were defined as uncomplicated dyspepsia. Results 4310 outpatients (mean age 44, median 42, range 14–86) were included in the final analyses. Significant pathology was found in 13.8% (595/4310) patients including peptic ulcer (12.3%) and upper gastrointestinal malignancy (1.5%). Age, male sex and alarm symptoms were significantly associated with malignancy. The age cut-off identified for upper gastrointestinal malignancy was 56 years among patients with uncomplicated dyspepsia, which was similar to the combined cutoff of age and gender. Conclusions Age should be considered as the primary predictor for upper gastrointestinal malignancy in Chinese patients with uncomplicated dyspepsia. 56 could probably be the optimal age to identify those lesions in this population. Trial registration: Chictr.org (ChiCTR2000040775).

Background Canadians are known to be frequent users of emergency department (ED) care. However, the exchange of information from ED visits to family physicians (FPs) is not well known. Our objectives were to determine whether Canadian FPs received information about their patient’s ED visit and the patient characteristics related to the receipt of ED information. Methods This study was a descriptive record linkage study of FP Electronic Medical Record (EMR) data linked to health administrative data. Our study cohort included patients who had at least one ED visit in 2010 or 2015 in Ontario, Canada. An ED visit could include a transfer to or from another ED. The receipt of information from an ED note was examined in relation to patient age, sex, neighbourhood income quintiles, rurality and comorbidity. Results There were 26,609 patients in 2010 and 50,541 patients in 2015 with at least one ED visit. In 2010, 53.3% of FPs received an ED note for patients having a single ED visit compared to 41.0% in 2015. For patients with multiple ED visits, 58.2% of FPs received an ED note in 2010 compared to 45.7% in 2015. FPs were more likely to receive an ED note for patients not living in low income neighbourhoods, older patients, patients living in small urban areas and for patients having moderate comorbidity. FPs were less likely to receive a note for patients living in rural areas. Conclusions Community-based FPs are more likely to get information after an ED visit for their older and sicker patients. However, FPs do not receive any information from EDs for over half their patients. Electronic health record technologies and their adoption by ED providers need to improve the seamless transfer of information about the care provided in EDs to FPs in the community.