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1.
Environ Pollut ; 292(Pt B): 118392, 2022 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-34678392

RESUMO

The short-term effects of ambient temperature on mortality have been widely investigated. However, the epidemiological evidence on the long-term effects of temperature on mortality is rare. In present study, we conducted a nationwide quasi-experimental design, which based on a variant of difference-in-differences (DID) approach, to examine the association between long-term exposure to ambient temperature and mortality risk in China, and to analyze the effect modification of population characteristics and socioeconomic status. Data on mortality were collected from 364 communities across China during 2006-2017, and environmental data were obtained for the same period. We estimated a 2.93 % (95 % CI: 2.68 %, 3.18 %) increase in mortality risk per 1 °C decreases in annual temperature, the greater effects were observed on respiratory diseases (5.16 %, 95 % CI: 4.53 %, 5.79 %) than cardiovascular diseases (3.43 %, 95 % CI: 3.06 %, 3.80 %), and on younger people (4.21 %, 95 % CI: 3.73 %, 4.68 %) than the elderly (2.36 %, 95 % CI: 2.06 %, 2.65 %). In seasonal analysis, per 1 °C decreases in average temperature was associated with 1.55 % (95 % CI: 1.23 %, 1.87 %), -0.53 % (95 % CI: -0.89 %, -0.16 %), 2.88 % (95 % CI: 2.45 %, 3.31 %) and 4.21 % (95 % CI: 3.98 %, 4.43 %) mortality change in spring, summer, autumn and winter, respectively. The effects of long-term temperature on total mortality were more pronounced among the communities with low urbanization, low education attainment, and low GDP per capita. In total, the decrease of average temperature in summer decreased mortality risk, while increased mortality risk in other seasons, and the associations were modified by demographic characteristics and socioeconomic status. Our findings suggest that populations with disadvantaged characteristics and socioeconomic status are vulnerable to long-term exposure of temperature, and targeted policies should be formulated to strengthen the response to the health threats of temperature exposure.

2.
Environ Res ; 203: 111834, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34358501

RESUMO

Age-specific discrepancy of mortality burden attributed to temperature, measured as years of life lost (YLL), has been rarely investigated. We investigated age-specific temperature-YLL rates (per 100,000) relationships and quantified YLL per death caused by non-optimal temperature in China. We collected daily meteorological data, population data and daily death counts from 364 locations in China during 2006-2017. YLL was divided into three age groups (0-64 years, 65-74 years, and ≥75 years). A distributed lag non-linear model was first employed to estimate the associations of temperature with age-specific YLL rates in each location. Then we pooled the associations using a multivariate meta-analysis. Finally, we calculated age-specific average YLL per death caused by temperature by cause of death and region. We observed greater effects of cold and hot temperature on YLL rates for the elderly compared with the young population by region or cause of death. However, YLL per death due to non-optimal temperature for different regions or causes of death decreased with age, with 2.0 (95 % CI:1.5, 2.5), 1.2 (1.1, 1.4) and 1.0 years (0.9, 1.2) life loss per death for populations aged 0-64 years, 65-74 years and over 75 years, respectively. Most life loss per death results from moderate temperature, especially moderate cold for all age groups. The effect of non-optimal temperature on YLL rates is smaller for younger populations than older ones, while the temperature-related life loss per death was more prominent for younger populations.

3.
Innovation (N Y) ; 2(4): 100171, 2021 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-34778857

RESUMO

Although studies have investigated the associations between PM2.5 and mortality risk, evidence from rural areas is scarce. We aimed to compare the PM2.5-mortality associations between urban cities and rural areas in China. Daily mortality and air pollution data were collected from 215 locations during 2014-2017 in China. A two-stage approach was employed to estimate the location-specific and combined cumulative associations between short-term exposure to PM2.5 (lag 0-3 days) and mortality risks. The excess risks (ER) of all-cause, respiratory disease (RESP), cardiovascular disease (CVD), and cerebrovascular disease (CED) mortality for each 10 µg/m3 increment in PM2.5 across all locations were 0.54% (95% confidence interval [CI]: 0.38%, 0.70%), 0.51% (0.10%, 0.93%), 0.74% (0.50%, 0.97%), and 0.52% (0.20%, 0.83%), respectively. Slightly stronger associations for CVD (0.80% versus 0.60%) and CED (0.61% versus 0.26%) mortality were observed in urban cities than in rural areas, and slightly greater associations for RESP mortality (0.51% versus 0.43%) were found in rural areas than in urban cities. A mean of 2.11% (attributable fraction [AF], 95% CI: 1.48%, 2.76%) of all-cause mortality was attributable to PM2.5 exposure in China, with a larger AF in urban cities (2.89% [2.12%, 3.67%]) than in rural areas (0.61% [-0.60%, 1.84%]). Disparities in PM2.5-mortality associations between urban cities and rural areas were also found in some subgroups classified by sex and age. This study provided robust evidence on the associations of PM2.5 with mortality risks in China and demonstrated urban-rural disparities of PM2.5-mortality associations for various causes of death.

4.
Front Surg ; 8: 755957, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34733883

RESUMO

Background: Transurethral resection of the prostate (TURP) is regarded as the "gold standard" for the treatment of benign prostatic hyperplasia (BPH) in elderly men. However, ~15% of patients who had undergone TURP had intraoperative and postoperative complications, such as bleeding, urinary incontinence and urethral stricture. Transperineal percutaneous laser ablation (TPLA) is a method that places the optical fibre directly into the prostate with the guidance of ultrasound imaging, and the percutaneous transperineal approach is performed distal to the urethra and rectum to protect these structures and reduce urethral or postoperative infection. Several studies on TPLA for BPH treatment have been reported recently; however, high-quality randomised controlled trial (RCT) to evaluate its efficacy, safety, and long-term follow up remain absent. Methods: This study is a multicentre, open-label RCT to assess the efficacy and safety of TPLA vs. TURP to treat BPH. We hypothesise that the TPLA has non-inferior efficacy to TURP in the International Prostate Symptom Score (IPSS) at 3 months changing from the baseline and lower incidence of post-surgery complications. One hundred and fourteen patients with BPH will be recruited at 19 sites and randomly assigned at 1:1 to TPLA or TURP groups. The patients will be followed up at 1, 3, 6, 12, and 24 months after the procedure. Discussion: The study will be the first multicentre clinical trial including 16 participating centres in China, Italy, Switzerland, and Poland with relatively large sample size 114. By comprehensively compare the safety and efficacy of TPLA with TURP in patients with BPH, especially concerning the improvement of lower urinary tract symptoms (LUTS) and complication incidence, the study will help to illustrate the clinical value of TPLA and provide a beneficial alternative treatment for BPH patients. Clinical Trial Registration: The study has been registered on Chinese Clinical Trial Registry (http://www.chictr.org.cn), identifier [ChiCTR1900022739].

5.
Indoor Air ; 2021 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-34796997

RESUMO

We hypothesized that exposure to polluting fuels for cooking was associated with abnormality of glucose metabolism and diabetes mellitus (DM) in south urban China. 3414 residents were surveyed in 14 urban areas of Guangdong Province in 2018. We recorded polluting fuels for cooking exposure, different DM status (DM, prediabetes), fasting blood glucose (FBG), oral glucose tolerance test (OGTT), glycated hemoglobin (HbA1c ), and other covariates by using a structured questionnaire. We conducted logistic regression model and multivariate linear regression model based on propensity-score method (inverse probability of weighting) to examine the effect of polluting fuels for cooking exposure on DM and glucose metabolism. Exposure to polluting fuels for cooking was associated with DM (odds ratio: 2.57, 95% confidence interval: 1.71 to 3.86) and prediabetes (odds ratio: 1.98, 95% confidence interval: 1.52 to 2.58) in both the adjusted and unadjusted models (all p < 0.05). Exposure to polluting fuels for cooking was significantly associated with an increase of FBG (ß: 0.30 mmol/L, 95% confidence interval: 0.22 to 0.38 mmol/L). Sensitivity analysis showed that the results were not substantially changed. There was an increased risk of DM, prediabetes and high levels of FBG, OGTT, and HbA1c among participants aged ≥ 40 years with exposure to polluting fuels for cooking. We demonstrated that exposure to polluting fuels for cooking was associated with higher levels of FBG, which contributed to the increased risk of DM and prediabetes in middle-aged elderly Chinese population living in urban areas.

6.
Zhongguo Fei Ai Za Zhi ; 24(10): 714-722, 2021 Oct 20.
Artigo em Chinês | MEDLINE | ID: mdl-34696543

RESUMO

With the development of precision medicine, therapies of targeting driver genes have significantly prolonged survival in advanced non-small cell lung cancer (NSCLC) patients. Among them, BRAF gene mutation is relatively rare, and the traditional regimen follows the treatment plan of NSCLC without driver gene mutation, which is far from meeting the clinical needs. In recent years, targeted therapy for NSCLC patients with BRAF V600E mutations has shown good efficacy when we are still exploring the better targeted therapies for other BRAF-mutated subtypes. Immunotherapy also showed positive antitumor activity in V600E and non-V600E subtypes of BRAF-mutated NSCLC. This article reviewed the progress of immunological and targeted therapy for patients with BRAF-mutated NSCLC.
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7.
Signal Transduct Target Ther ; 6(1): 355, 2021 10 15.
Artigo em Inglês | MEDLINE | ID: mdl-34650034

RESUMO

This multicenter phase-II trial aimed to investigate the efficacy, safety, and predictive biomarkers of toripalimab plus chemotherapy as second-line treatment in patients with EGFR-mutant-advanced NSCLC. Patients who failed from first-line EGFR-TKIs and did not harbor T790M mutation were enrolled. Toripalimab plus carboplatin and pemetrexed were administrated every three weeks for up to six cycles, followed by the maintenance of toripalimab and pemetrexed. The primary endpoint was objective-response rate (ORR). Integrated biomarker analysis of PD-L1 expression, tumor mutational burden (TMB), CD8 + tumor-infiltrating lymphocyte (TIL) density, whole-exome, and transcriptome sequencing on tumor biopsies were also conducted. Forty patients were enrolled with an overall ORR of 50.0% and disease-control rate (DCR) of 87.5%. The median progression free survival (PFS) and overall survival were 7.0 and 23.5 months, respectively. The most common treatment-related adverse effects were leukopenia, neutropenia, anemia, ALT/AST elevation, and nausea. Biomarker analysis showed that none of PD-L1 expression, TMB level, and CD8 + TIL density could serve as a predictive biomarker. Integrated analysis of whole-exome and transcriptome sequencing data revealed that patients with DSPP mutation had a decreased M2 macrophage infiltration and associated with longer PFS than those of wild type. Toripalimab plus chemotherapy showed a promising anti-tumor activity with acceptable safety profiles as the second-line setting in patients with EGFR-mutant NSCLC. DSPP mutation might serve as a potential biomarker for this combination. A phase-III trial to compare toripalimab versus placebo in combination with chemotherapy in this setting is ongoing (NCT03924050).

8.
Innovation (N Y) ; 2(1): 100072, 2021 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-34557729

RESUMO

Although numerous studies have investigated premature deaths attributable to temperature, effects of temperature on years of life lost (YLL) remain unclear. We estimated the relationship between temperatures and YLL, and quantified the YLL per death caused by temperature in China. We collected daily meteorological and mortality data, and calculated the daily YLL values for 364 locations (2013-2017 in Yunnan, Guangdong, Hunan, Zhejiang, and Jilin provinces, and 2006-2011 in other locations) in China. A time-series design with a distributed lag nonlinear model was first employed to estimate the location-specific associations between temperature and YLL rates (YLL/100,000 population), and a multivariate meta-analysis model was used to pool location-specific associations. Then, YLL per death caused by temperatures was calculated. The temperature and YLL rates consistently showed U-shaped associations. A mean of 1.02 (95% confidence interval: 0.67, 1.37) YLL per death was attributable to temperature. Cold temperature caused 0.98 YLL per death with most from moderate cold (0.84). The mean YLL per death was higher in those with cardiovascular diseases (1.14), males (1.15), younger age categories (1.31 in people aged 65-74 years), and in central China (1.34) than in those with respiratory diseases (0.47), females (0.87), older people (0.85 in people ≥75 years old), and northern China (0.64) or southern China (1.19). The mortality burden was modified by annual temperature and temperature variability, relative humidity, latitude, longitude, altitude, education attainment, and central heating use. Temperatures caused substantial YLL per death in China, which was modified by demographic and regional characteristics.

9.
Int J Med Sci ; 18(15): 3615-3623, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34522189

RESUMO

Background: Because the halo around the tumor in shear wave elastography (SWE) is defined as the "stiff rim" sign, the diagnosis of breast lesions with the stiff rim sign is popular. However, only a few studies have described the stiff rim sign quantitatively. Objective: This study aimed to investigate the usefulness of the stiff rim sign in the diagnosis and tumor, node, metastasis stage of breast cancer. Methods: Two hundred and ten breast lesions were analyzed retrospectively. The maximum, mean, minimum Young's modulus (YM), and the YM standard deviation in the lesion, the peritumoral stiffness (shell), and the region containing lesion and shell were obtained. The suspicious SWE feature with the best diagnostic performance was chosen to downgrade or upgrade the Breast Imaging Reporting and Data System (BI-RADS) classification. The coincidence rates of SWE and B-mode ultrasound in T staging and their positive predictive value (PPV) for T staging were compared. Results: The presence of "stiff rim" sign was selected to upgrade or downgrade the BI-RADS classification because of its best performance. In pathological benign lesions, 18.9% (25 of 132) of lesions should undergo biopsy if BI-RADS combined with the stiff rim sign were referred while it was 57.6% (76 of 132) if BI-RADS alone was referred. The coincidence rate of T2 staging evaluated by SWE was significantly higher than B-mode ultrasound (about 30% increase, P < 0.001). The PPVs of SWE for T1 and T2 staging were higher than B-mode ultrasound (P < 0.05). Conclusions: BI-RADS combined with "stiff rim" sign is expected to improve the diagnostic performance of breast lesions to avoid unnecessary biopsy. The maximum diameter of the lesion measured in SWE is more accurate than B-mode ultrasound in the estimation of T staging, which is beneficial to the treatment and prognosis of breast cancer.

10.
Front Oncol ; 11: 720044, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34504796

RESUMO

Objectives: To examine the long-term survival outcome of dabrafenib in combination with trametinib in Chinese patients with unresectable or metastatic acral/cutaneous melanoma with BRAF-V600 mutation and to explore potential predictors of effectiveness. Methods: This was a long-term follow-up of Chinese patients with unresectable or metastatic BRAF V600-mutant acral/cutaneous melanoma administered dabrafenib (150 mg twice daily) plus trametinib (2 mg once daily) in an open-label, multicenter, single-arm, phase IIa study (NCT02083354). Efficacy endpoints included objective response rate (ORR), duration of response (DOR), progression-free survival (PFS), and overall survival (OS). The impacts of baseline characteristics on PFS and OS were analyzed. Results: A total of sixty patients were included. The median age was 48 years, and 24 patients (40.0%) were male. Totally 12 individuals (20.0%) had acral melanoma, and 45 (75.0%) had failed previous systemic therapy. Up to July 2020, the median duration of follow-up was 37.0 (95% confidence interval [CI] 29.1-44.9) months. The updated ORR was 71.7% (95%CI 60.3%-83.1%). The 3-year OS rate was 28.8% (95%CI 19.1-43.6%) in the overall population, and 35.7% (95%CI 15.5-82.4%) in acral melanoma patients. The median DOR was 7.5 months (95%CI 4.5 to 10.5). Baseline normal lactic dehydrogenase (LDH), metastatic organ sites<3 and complete response to combination therapy with dabrafenib plus trametinib were associated with improved PFS and OS. Conclusion: Dabrafenib combined with trametinib confer long-term survival in Chinese patients with BRAF V600-mutant, unresectable or metastatic acral/cutaneous melanoma. Clinical Trial Registration: https://clinicaltrials.gov/ct2/show/NCT02083354, identifier NCT02083354.

11.
J Sep Sci ; 44(20): 3860-3869, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34384003

RESUMO

Methoxyfenozide and metaflumizone are insecticides used on Chinese broccoli to prevent insects and increase yield. However, the residues are potentially harmful to the environment and consumers. In this study, the quick, easy, cheap, effective, rugged, safe method with high-performance liquid chromatography with tandem mass spectrometry was modified and validated for determination of methoxyfenozide and metaflumizone in Chinese broccoli. The clean-up efficiency of different sorbents including C18 , primary secondary amine, graphitized carbon black, and carbon nanofiber was compared. Recoveries of the validated method were 71.8-94.6% with relative standard deviations of 1.5-3.2% and the limits of quantification were 0.01 and 0.005 mg/kg for methoxyfenozide and metaflumizone, respectively. A storage stability test showed almost no degradation of methoxyfenozide in Chinese broccoli, however, the degradation rate of metaflumizone was 22.9% after 10-wk storage at -20°C. In field trials in four producing regions, the dissipation of both methoxyfenozide and metaflumizone in Chinese broccoli was fast, with half-lives of only 1.0-5.1 and 0.7-2.5 days, respectively. Terminal residues after application of the two pesticides were all below 1.0 mg/kg after 5 days.

12.
BMC Public Health ; 21(1): 1534, 2021 08 11.
Artigo em Inglês | MEDLINE | ID: mdl-34380442

RESUMO

BACKGROUND: There existed evidence that type 2 diabetes mellitus (T2DM) prevalence and control rate have seasonal variation. Our study aimed to examine the ambient temperature and fasting plasma glucose (FPG) association and estimate temperature-adjusted T2DM prevalence and control rate. METHODS: Four cross-sectional health surveys with 26,350 respondents were conducted in Guangdong Province from 2007 to 2015. Multistage cluster sampling was used to recruit study participants. The data of demographic characteristics, lifestyle factors, diet and use of hypoglycemic medicine, height, weight, FPG and meteorological information were collected. And an inverse distance-weighted method was employed to estimate daily temperature exposures at the individual' s residential district/county. Base on World Health Organization 2006 criteria, participants were divided into normal fasting glucose (NFG) participants (n = 23,877), known T2DM patients (n = 916) and newly detected T2DM patients (n = 1557). Generalized additive mixed model was employed to evaluate the nonlinear associations between temperature and FPG among different T2DM subgroups. The T2DM prevalence and control rate were estimated based on temperature-FPG association. RESULTS: The curves of temperature and FPG were downward parabola for total, NFG and known T2DM groups, while it was "U"-shaped for newly detected T2DM patients. When temperature decreased from 30 °C to 4 °C, the FPG significantly increased 0.24 (95%CI: 0.15, 0.33) mmol/L, 0.10 (95%CI: 0.06, 0.14) mmol/L and 1.34 (95%CI: 0.56, 2.12) mmol/L in total, NFG and known T2DM groups, respectively. Compared to 19 °C, newly detected T2DM patients' FPGs were increased 0.73 (95%CI: 0.13, 1.30) mmol/L at 4 °C and 0.53 (0.00, 1.07) mmol/L at 30 °C. The model-estimated temperature-adjusted T2DM prevalence had a down and up trend, with 9.7% at 5 °C, 8.9% at 20 °C and 9.4% at 30 °C, respectively. At 5, 10, 15, 20, 25 and 30 °C, the model-estimated temperature-adjusted T2DM control rates were 33.2, 35.4, 38.2, 43.6, 49.1 and 55.2%. CONCLUSION: Temperature was negatively associated with FPG for NFG and known T2DM subgroups, while their association was U-shape for newly detected T2DM patients. Hence, the temperature-adjusted T2DM prevalence show a dip/peak pattern and T2DM control rate display a rising trend when temperature increase. Our findings suggest temperature should be considered in T2DM clinic management and epidemiological survey.


Assuntos
Glicemia , Diabetes Mellitus Tipo 2 , China/epidemiologia , Estudos Transversais , Diabetes Mellitus Tipo 2/epidemiologia , Jejum , Humanos , Prevalência , Temperatura
13.
Adv Sci (Weinh) ; 8(15): 2003241, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34377627

RESUMO

An elastic and safe electrolyte is demanded for flexible batteries. Herein, a stretchable solid electrolyte comprised of crosslinked elastic polymer matrix, poly(vinylidene fluoride-hexafluoropropylene) (PVDF-HFP), and flameproof triethyl phosphate (TEP) is fabricated, which exhibits ultrahigh elongation of 450%, nonflammability and ionic conductivity above 1 mS cm-1. In addition, in order to improve the interface compatibility between the electrolyte and Li anode and stabilize the solid-electrolyte interphase (SEI), a protecting layer containing poly(ethylene oxide) (PEO) is designed to effectively prevent the anode from reacting with TEP and optimize the chemical composition in SEI, leading to a tougher and more stable SEI on the anode. The LiFePO4/Li cells employing this double-layer electrolyte exhibit an 85.0% capacity retention after 300 cycles at 1 C. Moreover, a flexible battery based on this solid electrolyte is fabricated, which can work in stretched, folded, and twisted conditions. This design of a stretchable double-layer solid electrolyte provides a new concept for safe and flexible solid-state batteries.

14.
Eur J Med Chem ; 225: 113765, 2021 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-34399391

RESUMO

Our previously reported carboxyl-containing DPP-4 inhibitors were highly potent but were poorly bioavailable. Esters of the carboxyl analogs exhibited a significant DPP-4 potency loss albeit with enhanced oral absorption. Herein, we described identification and structure-activity relationship (SAR) exploration of a novel series of benzoic acid and ester derivatives as low single-digit nanomolar DPP-4 inhibitors. Importantly, the esters displayed comparable activities to the acids counterparts. Molecular simulation revealed that ester adopts a similar binding mode to acid. Moreover, the selected esters and acids demonstrated high selectivity and low cytotoxicity, as well as good metabolic stability. And more importantly, the esters possessed excellent pharmacokinetic profiles for oral administration. The best compound ester 19b demonstrated long DPP-4 inhibition in vivo, and robustly improved the glucose tolerance in normal and db/db mice while ensuring glucose-lowering potency in chronic treatment. Our results supported that the compound 19b can be served as a potential candidate for the treatment of type 2 diabetes.

15.
J Transl Med ; 19(1): 296, 2021 07 08.
Artigo em Inglês | MEDLINE | ID: mdl-34238310

RESUMO

BACKGROUND: Immunotherapy is a revolutionary strategy in cancer therapy, but the resistance of which is one of the important challenges. Detecting the regulation of immune cells and biomarkers concerning immune checkpoint blockade (ICB) therapy is of great significance. METHODS: Here, we firstly constructed regulation networks for 11 immune cell clusters by integrating biological pathway data and single cell sequencing data in metastatic melanoma with or without ICB therapy. We then dissected these regulation networks and identified differently expressed genes between responders and non-responders. Finally, we trained and validated a logistic regression model based on ligands and receptors in the regulation network to predict ICB therapy response. RESULTS: We discovered the regulation of genes across eleven immune cell stats. Functional analysis indicated that these stat-specific networks consensually enriched in immune response corrected pathways and highlighted antigen processing and presentation as a core pathway in immune cell regulation. Furthermore, some famous ligands like SIRPA, ITGAM, CD247and receptors like CD14, IL2 and HLA-G were differently expressed between cells of responders and non-responders. A predictive model of gene sets containing ligands and receptors performed accuracy prediction with AUCs above 0.7 in a validation dataset suggesting that they may be server as biomarkers for predicting immunotherapy response. CONCLUSIONS: In summary, our study presented the gene-gene regulation landscape across 11 immune cell clusters and analysis of these networks revealed several important aspects and immunotherapy response biomarkers, which may provide novel insights into immune related mechanisms and immunotherapy response prediction.


Assuntos
Biomarcadores Tumorais , Melanoma , Biomarcadores Tumorais/genética , Humanos , Imunoterapia , Melanoma/genética , Melanoma/terapia
16.
Otol Neurotol ; 42(9): e1313-e1317, 2021 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-34121084

RESUMO

OBJECTIVE: Many authors, including us, elucidated that vitamin D deficiency was a risk factor for benign paroxysmal position vertigo. We speculated vitamin D deficiency was likely to intervene otoconia formation by globular substance (GS). METHODS: Kunming mice were randomly divided into three groups: vitamin D sufficient group (12-wk standard control diet), vitamin D deficiency group (16-wk vitamin D deficiency diet), and vitamin D supplement group (16-wk vitamin D deficiency diet and followed 8-wk standard control diet). At 12, 16, and 24 weeks, blood was collected for measuring vitamin D and macula utriculi were obtained for research under scanning electron microscope (SEM). We randomly selected 10 SEM photographs of macula utriculi in each mouse, counted cilium and GS, and measured diameters of counted GS. The ratio of the number of GS to cilium in each SEM photograph was defined as density of GS. RESULTS: The diameter and density of GS were larger and higher in vitamin D deficiency group than sufficient group (p < 0.05; p < 0.05). There was no significant difference in density and diameters of GS between vitamin D deficiency and supplement group. The rough and grainy surface became smoother and smoother along with vitamin D deficiency, and reappeared after vitamin D supplement for 8 weeks. CONCLUSION: GS secreted as a precursor of mature otoconia is affected by vitamin D deficiency and vitamin D supplementation can mitigate the effects in mice. The density of GS, a quantitative method we designed, can quantify GS well.


Assuntos
Deficiência de Vitamina D , Animais , Vertigem Posicional Paroxística Benigna , Dieta , Camundongos , Membrana dos Otólitos , Vitamina D , Deficiência de Vitamina D/complicações , Deficiência de Vitamina D/tratamento farmacológico
17.
Genomics ; 113(4): 2683-2694, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34129933

RESUMO

The AJCC staging system is considered as the golden standard in clinical practice. However, it remains some pitfalls in assessing the prognosis of gastric cancer (GC) patients with similar clinicopathological characteristics. We aim to develop a new clinic and genetic risk score (CGRS) to improve the prognosis prediction of GC patients. We established genetic risk score (GRS) based on nine-gene signature including APOD, CCDC92, CYS1, GSDME, ST8SIA5, STARD3NL, TIMEM245, TSPYL5, and VAT1 based on the gene expression profiles of the training set from the Asian Cancer Research Group (ACRG) cohort by LASSO-Cox regression algorithms. CGRS was established by integrating GRS with clinical risk score (CRS) derived from Surveillance, Epidemiology, and End Results (SEER) database. GRS and CGRS dichotomized GC patients into high and low risk groups with significantly different prognosis in four independent cohorts with different data types, such as microarray, RNA sequencing and qRT-PCR (all HR > 1, all P < 0.001). Both GRS and CGRS were prognostic signatures independent of the AJCC staging system. Receiver operating characteristic (ROC) analysis showed that area under ROC curve of CGRS was larger than that of the AJCC staging system in most cohorts we studied. Nomogram and web tool (http://39.100.117.92/CGRS/) based on CGRS were developed for clinicians to conveniently assess GC prognosis in clinical practice. CGRS integrating genetic signature with clinical features shows strong robustness in predicting GC prognosis, and can be easily applied in clinical practice through the web application.

18.
Thorac Cancer ; 12(15): 2170-2181, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34128337

RESUMO

BACKGROUND: The prognosis for patients with stage II/III non-small cell lung cancer (NSCLC) is unsatisfactory, even after complete tumor resection and adjuvant chemotherapy. Here, we assessed the prognostic and predictive value of immunogenomic signatures for stage II/III NSCLC in Chinese patients. METHODS: A total of 91 paired resected stage II/III NSCLC and normal tissues, including 47 squamous cell lung carcinomas (SCC) and 44 lung adenocarcinomas (ADC), were collected and analyzed using whole exome sequencing (WES) to identify immunogenomic signatures for association with clinicopathological variables and disease-free survival (DFS). RESULTS: Higher neoantigen load (NAL, >2 neoantigens/Mb) exhibited better DFS for SCC patients (p = 0.021) but not ADC patients. A benefit from adjuvant chemotherapy was correlated with lower NAL (≤2 neoantigens/Mb) (p = 0.009). However, tumor mutation burden (TMB), mutations of individual gene, oncogene pathways, and antigen presentation machinery genes, and human leukocyte antigen (HLA)-I number and HLA-I loss of heterozygosity (LOH) had no prognostic or predictive value for DFS of SCC or ADC patients. CONCLUSIONS: NAL is a useful biomarker for lung SCC prognosis and prediction of chemotherapy responses in Chinese patients. The predictive value of NAL for adjuvant immunotherapy should be further explored in patients with resected NSCLC.

19.
BMJ Open ; 11(6): e045317, 2021 06 02.
Artigo em Inglês | MEDLINE | ID: mdl-34083336

RESUMO

OBJECTIVE: We aimed to ascertain the trends of injury mortality during the COVID-19 period in southern China. METHODS: We conducted a population-based retrospective analysis to compare the mortality changes of all-cause injury and transport injuries, poisoning, falls, fire/heat/hot substances, drowning, self-harm and interpersonal violence, which were further stratified by sex and age. Comparisons were made between the COVID-19 period (between January 2020 and June 2020) and control period (between January 2019 and June 2019) in Guangdong province. We used the negative binomial models to explore the associations of deaths during the COVID-19 period, according to the different sex and age strata. RESULTS: The all-cause injury mortality in Guangdong province decreased significantly from 28.65 per 100 000 population during the control period to 23.24 per 100 000 population during COVID-19 pandemic period. Similar results were found in specific injury categories. Mortality of self-harm increased by 139.26% in the 10-14 year group during the COVID-19 period as compared with the control period. Although mortality changes in some groups were not statistically significant, some increases were noteworthy during the COVID-19 period (ie, self-harm, transport injury and falls) in the 70-79 year group. The corresponding increase in mortality rate was 16.83%, 3.32% and 4.92%, respectively. CONCLUSION: The mortality of all-cause injury, transport injury and drowning during the COVID-19 pandemic was consistently decreased. However, the increase in mortality associated with falls, fire/heat/hot substance injury and self-harm in specific age populations warrant the targeted control and prevention measures for the population at risk.


Assuntos
COVID-19 , Suicídio , Ferimentos e Lesões , China/epidemiologia , Humanos , Pandemias , Estudos Retrospectivos , SARS-CoV-2
20.
Postgrad Med J ; 2021 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-33990394

RESUMO

OBJECTIVES: To analyse the patterns of transition of health burden for 110 causes of death by stratification of age, sex and geographic regions in Guangdong between 2005 and 2015. METHODS: We analysed the age-specific, sex-specific, region-specific mortality in Guangdong based on assembled databases. County-level surveillance data were calculated to inform city-level changes. RESULTS: The age-standardised mortality of all causes, non-communicable diseases (NCDs), communicable diseases, maternal diseases, neonatal diseases, malnutrition and injury declined progressively. Despite declining mortality of NCDs, the overall burden of disease was dominated by NCDs (ie, cerebrovascular disease, chronic obstructive pulmonary disease) that still accounted for 86.93% and 88.12% of death in 2005 and 2015, respectively. Considerable variations across geographic regions were observed (lowest in Pearl River Delta and highest in west Guangdong). There was a modest shift to transport injuries at younger ages and unintentional injuries in the elderly. CONCLUSIONS: We have documented a dramatic change in the overall mortality and age-specific, sex-specific and cause-specific mortality in Guangdong province between 2005 and 2015. The significant burden of NCDs remains a major healthcare issue despite the notable progress in reducing mortality in Guangdong, China. Our findings highlight important unmet needs to refine healthcare services by taking into account the inequity of age, sex and geographic regions. Identification of the 'treatable' risk factors and improved disease surveillance should be continuously improved to minimised the overall and cause-specific mortality.

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