Resting heart rate is associated with the risk of metabolic syndrome and its components among Dong adults in southwest China: Cross-sectional findings of the China Multi-Ethnic Cohort Study.

AIMS: High resting heart rate (RHR), one abnormal manifestation of autonomic nervous system, is associated with metabolic disorders. However, the association between RHR and metabolic syndrome (MetS) and its components remains controversial. We aimed to explore the link between these two parameters. MATERIALS AND METHODS: The study included 6589 Dong adults (1434 cases of MetS) from the cross-sectional survey of the China Multi-Ethnic Cohort Study. Logistic regression model was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs) and assess the association between RHR and MetS, clustered metabolic risk, and MetS components. Restricted cubic splines model was used to evaluate the dose response association. RESULTS: A positive association existed between RHR and MetS, and people in the highest RHR quartile had a higher MetS risk (OR 1.75 [95% CI 1.42-2.15]) than those in the lowest quartile. The clustered metabolic risk associated with RHR (p < 0.05). Furthermore, RHR was related to elevated blood pressure (BP), elevated triglycerides (TG) and elevated fasting plasma glucose (FPG); the ORs (95% CIs) for the highest versus lowest RHR quartile were 2.06 (1.75-2.43), 1.37 (1.17-1.62) and 2.53 (2.04-3.14), respectively. Similar results were found in sensitivity and subgroup analyses. Also, non-linear dose response association existed between RHR and MetS and elevated levels of BP, TG and FPG (p < 0.001). CONCLUSIONS: RHR was related to increased risk of MetS, three MetS components (elevated BP, elevated TG and elevated FPG) and the clustered metabolic risk. RHR may be a useful indicator for MetS.

Age-Stratified Cut-Off Values for Serum Levels of N-Terminal ProB-Type Natriuretic Peptide and Mortality from Sepsis in Children Under Age 18 Years: A Retrospective Study from a Single Center.

BACKGROUND The N-terminal fragment of proB-type natriuretic peptide (NT-proBNP) is an established predictive marker for sepsis-related mortality in adult. This retrospective study aimed to determine age-stratified cut-off values for serum levels of NT-proBNP and mortality from sepsis in children under 18 years. MATERIAL AND METHODS Patients were stratified by age as follows: <1 year, 1-3 years, 4-6 years, and 7-18 years (age groups). The control group consisted of age- and sex-matched healthy children. Serum NT-proBNP levels were detected by laboratory assays in the participants. The appropriate serum NT-proBNP cut-off values for predicting short-term mortality of the sepsis patients were calculated via receiver operating characteristic (ROC) curve analyses. RESULTS Among 327 pediatric patients with sepsis, the serum NT-proBNP cut-off concentrations for predicting sepsis-related mortality in the <1 year, 1-3 years, 4-6 years, and 7-18 years age groups were 5000 ng/L, 4500 ng/L, 4100 ng/L, and 3800 ng/L, respectively (P<0.001). The area under the ROC curve (AUC) values for these were 0.815, 0.812, 0.806 and 0.725, respectively (P<0.001). CONCLUSIONS This retrospective study provided the age range-specific serum NT-proBNP cut- off concentrations for predicting short-term mortality in children. In children <1 year, 1-3 years, 4-6 years, and 7-18 years, age-stratified cut-off values that predicted sepsis-associated mortality were 5000 ng/L, 4500 ng/L, 4100 ng/L, and 3800 ng/L, respectively.

Dose-response association between sugar- and artificially sweetened beverage consumption and the risk of metabolic syndrome: a meta-analysis of population-based epidemiological studies.

OBJECTIVE: The associations between sugar-sweetened beverage (SSB) and artificially sweetened beverage (ASB) consumption and the risk of metabolic syndrome (MetS) remain controversial. A quantitative assessment of dose-response associations has not been reported. This study aims to assess the associations between the risk of MetS and SSB, ASB, and total sweetened beverage (TSB, the combination of SSB and ASB) consumption by reviewing population-based epidemiological studies. DESIGN: Meta-analysis. SETTING: We searched PubMed, Embase and Web of Science databases prior to 4 November 2019, for relevant studies investigating the SSB-MetS and ASB-MetS associations. A random effects model was used to estimate pooled relative risks (RR) and 95 % CI. Dose-response association was assessed using a restricted cubic splines model. PARTICIPANTS: We identified seventeen articles (twenty-four studies, including 93 095 participants and 20 749 MetS patients). RESULTS: The pooled RR for the risk of MetS were 1·51 (95 % CI 1·34, 1·69), 1·56 (1·32, 1·83) and 1·44 (1·19, 1·75) in high consumption group of TSB, SSB and ASB, respectively; and 1·20 (1·13, 1·28), 1·19 (1·11, 1·28) and 1·31 (1·05, 1·65) per 250 ml/d increase in TSB, SSB and ASB consumption, respectively. Additionally, we found evidence of non-linear, TSB-MetS and SSB-MetS dose-response associations and a linear ASB-MetS dose-response association. CONCLUSIONS: TSB, SSB and ASB consumption was associated with the risk of MetS. The present findings provide evidence that supports reducing intake of these beverages to lower the TSB-, SSB- and ASB-related risk of MetS.

A systematic and meta-analysis of heterosexual behaviors and HIV prevalence among Chinese men who have sex with men.

Men who have sex with men (MSM) are potentially at high risk for HIV infection, their HIV prevalence far exceeds the national prevalence rate. There are also a number of MSM who have sex with women, mostly unprotected, which can transmit HIV to their female sexual partners and even to the next generation. The purpose of this article is to evaluate the prevalence of heterosexual behaviors in Chinese men who have sex with men and the status of condom utilization as well as HIV infection among MSM with heterosexual behaviors, so as to further improve the investigation and prevention and control of AIDS in MSM population. We systematically searched China National Knowledge Infrastructure, Wanfang Data, VIP Database for Chinese Technical Calligraphy (VIP), Pubmed, and Embase following certain retrieval strategies to find relevant articles published from January 1, 2015 to November 18, 2019, The useful information extracted from qualified articles, Stata 15.1 and Review Manager 5.3 were employed for further meta analysis. The estimated prevalence of heterosexual behaviors among MSM in the past year was 19.0% (95% CI 17.0%, 22.0%). The estimated condom utilization rate of the last heterosexual behavior among MSM and condom adherence rate of heterosexual behaviors among MSM were 51.0% (95% CI 44.0%, 58.0%) and 31.0% (95% CI 25.0%, 38.0%), respectively. And the pooled HIV prevalence in MSM with heterosexual behaviors was 9% (95% CI 6%, 13%). The sensitivity analysis showed that the results were stable. No publication bias was found by Egger's test. There is a high proportion of MSM with heterosexual behaviors and low condom utilization in China. HIV prevalence in MSM with heterosexual behaviors is also high. Therefore, adequate attention should be given to this particular group and measures should be taken in order to reduce the risk of transmission of HIV from subpopulations to the general population.

Renal interstitial cells promote nephron regeneration by secreting prostaglandin E2.

In organ regeneration, progenitor and stem cells reside in their native microenvironment, which provides dynamic physical and chemical cues essential to their survival, proliferation, and differentiation. However, the types of cells that form the native microenvironment for renal progenitor cells (RPCs) have not been clarified. Here, single-cell sequencing of zebrafish kidney reveals fabp10a as a principal marker of renal interstitial cells (RICs), which can be specifically labeled by GFP under the control of fabp10a promoter in the fabp10a:GFP transgenic zebrafish. During nephron regeneration, the formation of nephrons is supported by RICs that form a network to wrap the RPC aggregates. RICs that are in close contact with RPC aggregates express cyclooxygenase 2 (Cox2) and secrete prostaglandin E2 (PGE2). Inhibiting PGE2 production prevents nephrogenesis by reducing the proliferation of RPCs. PGE2 cooperates with Wnt4a to promote nephron maturation by regulating ß-catenin stability of RPC aggregates. Overall, these findings indicate that RICs provide a necessary microenvironment for rapid nephrogenesis during nephron regeneration.

Proenkephalin-A secreted by renal proximal tubules functions as a brake in kidney regeneration.

Organ regeneration necessitates precise coordination of accelerators and brakes to restore organ function. However, the mechanisms underlying this intricate molecular crosstalk remain elusive. In this study, the level of proenkephalin-A (PENK-A), expressed by renal proximal tubular epithelial cells, decreases significantly with the loss of renal proximal tubules and increased at the termination phase of zebrafish kidney regeneration. Notably, this change contrasts with the role of hydrogen peroxide (H2O2), which acts as an accelerator in kidney regeneration. Through experiments with penka mutants and pharmaceutical treatments, we demonstrate that PENK-A inhibits H2O2 production in a dose-dependent manner, suggesting its involvement in regulating the rate and termination of regeneration. Furthermore, H2O2 influences the expression of tcf21, a vital factor in the formation of renal progenitor cell aggregates, by remodeling H3K4me3 in renal cells. Overall, our findings highlight the regulatory role of PENK-A as a brake in kidney regeneration.

Yield, NNS and prevalence of screening for DM and hypertension among pulmonary tuberculosis index cases and contacts through single time screening: A contact tracing-based study.

INTRODUCTION: Diabetes mellitus (DM), hypertension and pulmonary tuberculosis (PTB) are catastrophic illnesses that collectively lead to increased mortality and premature death. However, the size of the problem and the appropriate approach to deal with the burden is still unclear. We aimed to evaluate the yield, number needed to screen (NNS) to prevent one death or adverse event for screening DM and hypertension and assess the prevalence and contributors to DM and/or hypertension. METHODS: Based on PTB contact tracing, a cross-sectional study was conducted among 801 PTB index cases and 972 household contacts from April 2019 to October 2020 in Guizhou, China. All the participants were screened for DM and hypertension. The yield was calculated as the proportion of newly detected cases among the study subjects, excluding known cases. The NNS was computed by dividing the number needed to treat for risk factors by the prevalence of the unrecognized diseases. The univariate and multivariate logistic regression analyses were applied to determine the independent predictors of DM and/or hypertension. RESULTS: Of the 1,773 participants, the prevalence of DM and hypertension was 8.7% (70/801) and 15.2% (122/801) in the PTB patients, 3.2% (31/972) and 14.0% (136/972) in the contacts, respectively. The prevalence of DM and/or hypertension was 21.2% (170/801) among the PTB patients and 15.4% (150/972) among their contacts. The screening yields to detect new cases of DM and hypertension among PTB patients were 1.9% and 5.2%, and that in the contacts were 0.8% and 4.8%, respectively. The NNS for DM was 359 for the PTB cases and 977 for the contacts, 299 for PTB cases and 325 for hypertension, respectively. Older age, under or overweight and obesity, family history hypertension and earlier diagnosis of other chronic conditions were the independent predictors for DM and/or hypertension among both PTB cases and their contacts. CONCLUSION: Screening for DM and hypertension should be mandated in PTB patients and their household contacts to disclose undetected cases of these two conditions during TB contact tracing, which might reduce the potential cardiovascular disease deaths.

Characterization of the complete mitochondrial genome of Coprinellus micaceus, a wild saprobic mushroom in China.

The Glistening Inkcap (Coprinellus micaceus) is a wild saprobic mushroom in China. In this study, we assembled and annotated its complete mitochondrial genome using raw data sequenced through Illumina NovaSeq 6000 platform (Illumina, San Diego, CA). The length of the C. micaceus mitochondrial genome is 65,450 bp with 33.05% GC content. Totally, 41 genes, including 14 protein-coding genes, 25 tRNAs and 2 rRNAs were identified in the mitochondrial genome. Phylogenetic analysis showed that the mitochondrial genome relationship between C. micaceus and Coprinopsis cinerea was the closest.

Establishment of a Drug Screening Model for Cardiac Complications of Acute Renal Failure.

Acute renal failure (ARF) is a clinical critical syndrome with rapid and severe decline of renal function. Complications of ARF, especially its cardiac complications (cardiorenal syndrome type 3, CRS-3), are the main causes of death in patients with ARF. However, the shortage and limited efficacy of therapeutic drugs make it significant to establish new large-scale drug screening models. Based on the Nitroreductase/Metronidazole (NTR/MTZ) cell ablation system, we constructed a Tg(cdh17:Dendra2-NTR) transgenic zebrafish line, which can specifically ablate renal tubular epithelial cells. The absence of renal tubular epithelial cells can lead to ARF in zebrafish larvae. The ARF symptoms, such as heart enlargement, slow heart rate and blood stasis, are similar to the clinical manifestations of human CRS-3. Furthermore, two therapeutic drugs (digoxin and enalapril) commonly used in the clinical treatment of heart failure were also effective in alleviating the symptoms of CRS-3 in zebrafish, which proved the effectiveness of this model. Drug screening further discovered a potential drug candidate, α-lipoic acid, which can effectively alleviate the symptoms of CRS-3 through its antioxidant function. Accordingly, we established a new ARF model of zebrafish, which laid a foundation for large-scale screening of new therapeutic drugs for its complications.

Otitis media in a mouse model for Down syndrome.

The Ts65Dn mouse shares many phenotypic characteristics of human Down syndrome. Here, we report that otitis media, characterized by effusion in the middle ear and hearing loss, was prevalent in Ts65Dn mice. Of the 53 Ts65Dn mice tested, 81.1% had high auditory-evoked brainstem response (ABR) thresholds for at least one of the stimulus frequencies (click, 8 kHz, 16 kHz and 32 kHz), in at least one ear. The ABR thresholds were variable and showed no tendency toward increase with age, from 2 to 7 months of age. Observation of pathology in mice, aged 3-4 months, revealed middle ear effusion in 11 of 15 Ts65Dn mice examined, but only in two of 11 wild-type mice. The effusion in each mouse varied substantially in volume and inflammatory cell content. The middle ear mucosae were generally thickened and goblet cells were distributed with higher density in the epithelium of the middle ear cavity of Ts65Dn mice as compared with those of wild-type controls. Bacteria of pathogenic importance to humans also were identified in the Ts65Dn mice. This is the first report of otitis media in the Ts65Dn mouse as a model characteristic of human Down syndrome.

Helicobacter pylori infection in the pharynx of patients with chronic pharyngitis detected with TDI-FP and modified Giemsa stain.

AIM: To detect whether there is Helicobacter pylori (H pylori) colonization in the pharynx mucous membrane of healthy people and whether chronic pharyngitis is related to H pylori infection. METHODS: Fifty cases of chronic pharyngitis refractory over three months were prospectively studied from March 2004 to August 2004 in the otolaryngology outpatient department of the Second Hospital of Xi'an Jiaotong University. Template-directed dye-terminator incorporated with fluorescence polarization detection (TDI-FP) and modified Giemsa stain were used to examine pharynx mucous membrane tissue for H pylori colonization in the patients with chronic pharyngitis and the healthy people as a control group. RESULTS: In the control group, no people were detected to have H pylori in the pharynx. In contrast, in 50 cases with chronic pharyngitis, 19 (38.0%) cases were H pylori positive with a TDI-FP assay and 4 (8%) cases were TDI-FP positive with Giemsa staining in the pharynx. Sixteen of the 50 pharyngitis cases had stomach ailment history, 11 cases (68.8%) of these 16 patients were determined to be H pylori positive in the pharynx with the TDI-FP assay. c2 test showed that this infection rate was remarkably higher (P=0.0007) than that in the cases without stomach ailment history. Giemsa staining showed that 3 cases (18.8%) of the patients with stomach ailment history were infected with H pylori in the pharynx, which was remarkably higher (P=0.042) than that in the patients without stomach ailment history (1 case, which was 2.9%). CONCLUSION: H pylori may not be detected in the pharynx of healthy people. Chronic pharyngitis may be related to H pylori infection. The infection rate with H pylori in the pharynx is higher in patients with stomach ailment histories than in patients without stomach ailment histories, suggesting that chronic pharyngitis may be related to stomach ailment history.

Observation of the morphology and calcium content of vestibular otoconia in rats after simulated weightlessness.

Reduction in bone formation may have been the main reason for the lower calcium content of the otoconia after simulated weightlessness in rats. The head-ward distribution of blood volume may explain the morphological changes observed in the middle and inner ears. To observe morphological changes in the vestibular organs and measure the calcium content of otoconia in rats after simulated weightlessness. We used a tail suspension model of simulated weightlessness and then investigated changes in the vestibular organs using scanning electron microscopy and X-ray microanalysis. In comparison to untreated rats, the vestibular otoconia of the rats subjected to simulated weightlessness were small, irregularly shaped or fissured, and were arranged loosely and out of order. In addition, the calcium content of the otoconia was markedly decreased.

Multifaceted regulation of somatic cell reprogramming by mRNA translational control.

Translational control plays a pivotal role in the regulation of the pluripotency network in embryonic stem cells, but its effect on reprogramming somatic cells to pluripotency has not been explored. Here, we show that eukaryotic translation initiation factor 4E (eIF4E) binding proteins (4E-BPs), which are translational repressors, have a multifaceted effect on the reprogramming of mouse embryonic fibroblasts (MEFs) into induced pluripotent stem cells (iPSCs). Loss of 4E-BP expression attenuates the induction of iPSCs at least in part through increased translation of p21, a known inhibitor of somatic cell reprogramming. However, MEFs lacking both p53 and 4E-BPs show greatly enhanced reprogramming resulting from a combination of reduced p21 transcription and enhanced translation of endogenous mRNAs such as Sox2 and Myc and can be reprogrammed through the expression of only exogenous Oct4. Thus, 4E-BPs exert both positive and negative effects on reprogramming, highlighting the key role that translational control plays in regulating this process.

Mutation in Phex gene predisposes BALB/c-Phex(Hyp-Duk)/Y mice to otitis media.

Genetic susceptibility underlying otitis media (OM) remains to be understood. We show in this study that mutation in Phex gene predisposes the BALB/c-Phex(Hyp-Duk)/Y (abbreviated Hyp-Duk/Y) mice to OM, which occurs at post-natal day 21 (P21) with an average penetrance of 73%. The OM was identified by effusion in the middle ear cavity and/or thickening of middle ear mucosae, and was characterised by increase in goblet cells, deformity of epithelial cilia and higher expression of proliferating cell nuclear antigen (PCNA) in cells of the middle ear mucosae. Moreover, the transcription levels of Tlr2, Tlr4, Nfkb1, Ccl4, Il1b and Tnfα in the ears of the Hyp-Duk/Y mice at P35 were significantly upregulated, compared to those of the controls. Higher expression levels of TLR2, TLR4, NF-κB and TNF-α in the middle ears were demonstrated by immunohistochemistry (IHC). However, the OM in the mice was not prevented by azithromycin administration from gestational day 18 to P35. Further study showed that, in contrast to the low mRNA levels of Phex gene in the ears of the Hyp-Duk/Y mice, the mRNA level of Fgf23 was significantly elevated at P9, P14, P21 and P35. Meanwhile, mRNA levels of EP2 (PGE2 receptor), which expressed in the middle ear epithelia as demonstrated by IHC, were already increased at P14 even before the occurrence of OM, indicating that PGE2, an inflammatory mediator, is involved in the OM development in the mutants. Taking together, Phex mutation primarily up-regulates gene expression levels in FGF23 mediated pathways in the middle ears, resulting in cell proliferation and defence impairment at the mucosae and subsequently bacterial infection. The Hyp-Duk/Y mouse is a new genetic mouse model of OM.

Small papillary tumor in the saccule.

Papillary tumors of the ear are aggressive neoplasms. Previously, a tumor growing in the saccule had not been reported. We report a tumor found incidentally in the saccule of a patient. Serial sections of both temporal bones of the patient were studied in order to analyze the tumor's origin and influence on audio vestibular function. In the right inner ear, there was a small papillary lesion in the saccule, which looked like a papillary tumor without aggression invasion. The tumor was located in the membranous labyrinth of the saccule, not in the endolymphatic duct and sac. It was not related to Von Hippel-Lindau (VHL) disease, nor was it an endolymphatic sac tumor. The tumor did not influence the hearing and vestibular function in the right ear, although this patient presented a severe sensorineural hearing loss and vestibular function loss because of the vestibular schwannoma in the left ear.