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Background Although several systematic reviews and meta-analyses have been conducted to assess the relationship between fruit intake and health outcomes, the results of the relationship are inconclusive. Scope and approach We conducted an umbrella evaluation of existing research on the relationship between fruit intake and various health outcomes in humans. We used A Measurement Tool to Assess Systematic Reviews 2 and Grade of Recommendations, Assessment, Development and Evaluation to comprehensively evaluate the methodological quality and evidence quality of the research. We also performed a subgroup analysis based on the study design. Key findings and conclusions The umbrella review covered 59 qualified studies, which included 77 meta-analyses and 66 health outcomes. No adverse relationships between fruit intake and health outcomes were found. Moderate-quality evidence suggested that one serving increment of fruit per day could decrease the risks of cardiovascular disease (RR: 0.97, 95% CI: 0.95 to 0.99), stroke (RR: 0.92, 95% CI: 0.88 to 0.96), coronary heart disease (RR: 0.96, 95% CI: 0.93 to 0.99), and oral cancer (OR: 0.51, 95% CI: 0.40 to 0.65). And moderate-quality evidence presented that 200 g increment of fruit intake per day was associated with lower risk of breast cancer (RR: 0.94, 95% CI: 0.89 to 0.99), and the risk of type 2 diabetes mellitus could be reduced by 8%-12% when the fruit intake increasing to 100-500 g/d. For the remaining studies, the quality of evidence was either low or very low. We also found that the study design could influence the significance of the association between fruit intake and health outcomes. Large-sample, multi-center, and multi-country randomized controlled trials or prospective studies are required to verify our results.

Background ETS transcription factors are known to act as either positive or negative regulators of the expression of genes involved in various biological processes. It was reported that ETS variant transcription factor 5 (ETV5), a key member of the ETS family, mainly plays a role as an potential oncogene in various malignant tumors. However, the role and mechanism of ETV5 in high-grade serous ovarian cancer (HGSOC) have not been elucidated. Methods Quantitative real-time polymerase chain reaction (qRT-PCR) assay was used to detect ETV5 messenger ribonucleic acid (mRNA) expression in 87 HGSOC tissues and 35 normal fallopian tube tissues. Western blotting and qRT-PCR were used to detect the protein and mRNA expression of ETV5 in six ovarian cancer (OC) and human embryonic cell lines. Knockdown or overexpression of ETV5 in HGSOC cell lines, Cell Counting Kit-8, colony formation, and transwell assays were used to detect HGSOC cell proliferation, invasion, and migration capabilities. The chi-square test was used to analyze the clinicopathological characteristics of HGSOC patients. Survival analysis was performed using the Kaplan-Meier method, and the log-rank test was used to analyze the correlation between ETV5 expression and HGSOC patient prognosis. Univariate and multivariate analyses using the Cox regression model were conducted to determine the independent significance of relevant clinical covariates. Results Bioinformatic analysis demonstrated that ETV5 expression was significantly upregulated in OC (p p Conclusion ETV5 has a carcinogenic effect in HGSOC and can be used as a clinically effective biomarker to determine the prognosis of HGSOC patients.

OBJECTIVE The study aimed to determine the safety and efficacy of intrathecally administered isoniazid (INH) and prednisolone in addition to systemic anti-TB therapy and compare it with systemic anti-TB therapy alone in adult patients with tuberculous meningitis (TBM). METHODS In this retrospective study, patients were categorized into two groups: Group A patients received systematic anti-TB therapy alone, Group B patients received IT INH (50 mg) and prednisolone (25 mg) twice a week together with the same standard systemic anti-TB therapy as Group A, in addition to the standard systemic anti-TB therapy. Functional outcomes were compared between the two groups in a prosperity-matched cohort using propensity score matching (PSM) method. RESULTS A total of 198 patients with TBM were enrolled. After PSM, 30 patients from each group were analyzed, so that there was no significant difference in the characteristics of the two groups. Mortality at follow-up was significantly lower among patients receiving additional IT therapy (4/30, 13.3%) compared with matched patients receiving systemic anti-TB therapy alone (11/30, 36.7%, P value = 0.037). CONCLUSIONS In this propensity score-matched cohort, the addition of IT INH and prednisolone to systemic anti-TB therapy could be effective for the better outcome among adult TBM patients. Further large-scale, prospective, and randomized controlled trials are warranted to the best timing and indication of IT therapy.

Background Dyslipidemia International Study II (DYSIS II)‐China was conducted to determine the low‐density lipoprotein cholesterol (LDL‐C) goal (

Objectives Cardiovascular disease (CVD) is leading cause of death in China. We aimed to provide national and subnational estimates and its change of premature mortality burden of CVD during 2005–2020. Methods Data from multi-source on the basis of national mortality surveillance system (NMSS) was used to estimate mortality and years of life lost (YLL) of total CVD and its subcategories in Chinese population across 31 provinces during 2005–2020. Results Estimated CVD deaths increased from 3.09 million in 2005 to 4.58 million in 2020; the age-standardized mortality rate (ASMR) decreased from 286.85 per 100,000 in 2005 to 245.39 per 100,000 in 2020. A substantial reduction of 19.27% of CVD premature mortality burden, as measured by age-standardized YLL rate, was observed. Ischemic heart disease (IHD), hemorrhagic stroke (HS) and ischemic stroke (IS) were leading 3 causes of CVD death. Marked differences were observed in geographical patterns for total CVD and its subcategories, and it appeared to be lower in areas with higher economic development. Population ageing was dominant driver contributed to CVD deaths increase, followed by population growth. And, age-specific mortality shifts contributed largely to CVD deaths decline in most provinces. Conclusion Substantial discrepancies were demonstrated in CVD premature mortality burden across China. Targeted considerations were needed to integrate primary care with clinical care through intensifying further strategies for reducing CVD mortality among specific subcategories, high risk population and regions with inadequate healthcare resources.

BACKGROUND: Krabbe disease, also called globoid cell leukodystrophy, is an autosomal recessive disease caused by a deficiency of lysosomal galactocerebrosidase. Infantile Krabbe occurring before 12 months of age accounts for most cases. Typical clinical features include irritability, seizures, peripheral neuropathy, and progressive neurodegeneration. METHODS: We collected and summarized the clinical and genetic data of an 8-month-old boy who demonstrated Krabbe disease onset at around 6 months. Potential pathogenic variants were screened by whole exome sequencing, and effects of candidate variants on alternative transcript and truncated protein were further validated at the RNA and protein level. RESULTS: Galactocerebrosidase activity was nearly absent in his blood, and whole exome sequencing revealed compound heterozygous variants [NM_000153.4: (c.658C>T); (c.328+5G>T)] in galactosylceramidase (GALC). The variant c.328+5G>T was predicted to alter splicing, and the abnormal isoform transcript was validated by observation of abnormal RNA isoforms. The variant c.658C>T was predicted to cause truncation of the protein, which was validated by western blotting. CONCLUSIONS: Our findings revealed compound heterozygous variants with solid experimental results for Krabbe disease and provides strong evidence for further Krabbe disease screening and clinical consulting. As a rare inherited systemic disorder, genetic variants in Krabbe disease should be investigated, as experimental validation for clinical diagnosis is needed.

The probability of toxicity-related myocardial injury event with anthracyclines is controversial, which could be related to the underlying cardiac status before chemotherapy. Our study sought to investigate the influence of cardiovascular risk factors on myocardial motion and cardiac function using layer-specific speckle tracking echocardiography (STE) during chemotherapy with epirubicin. Female patients with first-diagnosed breast cancer were prospectively enrolled in our study and received 4 chemotherapeutic cycles with epirubicin in each cycle of 21 days. All patients underwent echocardiography for layer-specific STE analysis before and after all chemotherapy. Clinical data including cardiovascular risk factors were collected. According to the Framingham score, patients with cardiovascular risk factors were divided into groups with low, medium, and high risk. 134 patients existed in the final analysis. The accumulated dose of epirubicin for were 560.0 ± 103.8 mg. 97 (72.4%) patients had cardiovascular risk factors. According to the Framingham score, 57 (42.5%) patients categorized in high risk. Endocardial layer strain after chemotherapy were lower than those at baseline (p

In recent years, immune checkpoint inhibitors (ICIs) have become a standard treatment for patients with advanced lung cancers. With the widespread use of immunotherapy in clinical practice, immune-related adverse events (irAEs) have become increasingly common. This case report details a 72-year-old man with small-cell lung cancer (SCLC) who developed pneumonitis, appendicitis, and biliary obstruction during treatment with toripalimab. The patient was initially diagnosed with limited-stage SCLC in January 2019 and completed 5 sequential cycles of etoposide/cisplatin (EP) and radiotherapy (60 Gy/30 F). The overall response was complete response (CR) after first line treatment. He developed radiation pneumonitis after completion of radiotherapy, which responded well to symptomatic treatment. Due to newly diagnosed bone metastasis, he was administered toripalimab intravenously every 3 weeks and 12 mg anlotinib orally once a day from January 2020. By the third cycle, the patient presented with electrocardiographic abnormalities, gingival swelling and pain, and hoarseness, and consequently, the anlotinib was suspended. After 4 cycles, he developed suppurative appendicitis, which was managed successfully with anti-inflammatory agents. He then presented with shortness of breath on exertion and after a comprehensive examination, he was diagnosed with ICI-related-pneumonitis. After 6 weeks of treatment with methylprednisolone, the shortness of breath was mostly relieved and treatment continued. In June 2020, the patient developed severe vomiting. Computed tomography (CT) indicated biliary obstruction, and at endoscopic retrograde cholangiopancreatography (ERCP) there was edema of the major papilla of the duodenum. The patient's symptoms were relieved after treatment with gastric acid suppression and antiemetics. Re-examination by magnetic resonance imaging (MRI) showed that the biliary obstruction had been resolved. Although the disease progressed after immunotherapy, no tumor tissue related to the biliary obstruction was detected, and this was therefore classified as an irAE.

We report a case of binocular retinitis pigmentosa (RP) with completely different visual acuity between 2 eyes, which may be contributed by the presence of cilioretinal arteries (CRAs) in 1 eye. A 66-year-old female patient complained of blurred vision after binocular cataract surgeries. Examinations revealed her right eye had 20/25 central visual acuity, but the fellow eye only had light perception. Subsequent fundus photography of both eyes firmed the diagnosis of binocular RP. However, there were some significant differences in retinal vessels, which were attenuated in her left eye in contrast to several spared retinal arterioles in the right eye. Optical coherence tomography angiography showed that the spared vessels might be CRAs. Our case provides an evidence that macular blood flow may contribute to the survival of cone cells in RP.

Regional disparities in cancer mortality rates are prevalent at all geographic scales. Area factors such as health conditions, behavior patterns, pollution, and socioeconomic status (SES) have sign...

This study was carried out to explore the promotion role of computed tomography (CT) imaging three-dimensional (3D) reconstruction technology and rapid rehabilitation nursing intervention (RRNI) in the treatment of patients with renal cell cancer (RCC) laparoscopic radical nephrectomy (LRN) in view of the patient’s condition. 98 RCC patients who were admitted to the hospital from July 2019 to July 2020 were selected as the research subjects, and all patients underwent the LRN and the RRIN. Of which, 46 RCC patients were scanned with CT images (regarded as the CT group), and 46 RCC patients were scanned with CT images based on 3D reconstruction algorithms (regarded as the 3D CT group). The clinical efficacy and the life quality, pain degree, and adverse mood changes before and after the RRN were analyzed and compared. The results showed that the surgery time in the 3D CT group and the CT group was 130.2 ± 42.8 minutes and 162.4 ± 38.5 minutes, respectively ( P < 0.05 ). The recurrence rate of RCC in both groups was 0%. The estimated blood loss in the 3D CT group and the CT group was 93.6 ± 35.5 mL and 90.3 ± 40.2 mL, respectively; the complication rate in the 3D CT and CT group was 5% and 12%, respectively; the hospital stay in the 3D CT and CT group was 12.5 ± 4.7 days and 12.1 ± 3.2 days, respectively, which had no statistical significance ( P > 0.05 ). The scores of visual analogue scale (VAS), 36-Item Short-Form Health Survey (SF-36), self-rating depression scale (SDS), and self-rating anxiety scale (SAS) of patients in the two groups were statistically significant ( P < 0.05 ). It indicated that CT images based on the 3D reconstruction algorithm could be applied in LRN of RCC patients to shorten the surgery time and improve the surgical effect, and implementation of the RRN could relieve the adverse mood of RCC patients and effectively improve their life quality.

Objective The eighth edition of the American Joint Committee on Cancer (AJCC‐v8) for anaplastic thyroid cancer (ATC) made a revision in staging for patients with lymph node metastasis (LNM) based on the seventh edition of AJCC (AJCC‐v7). Our study aimed to evaluate the predictive ability of AJCC‐v8 for survival in patients with ATC by exploring the association between lymph node stage and prognosis of ATC patients. Methods Retrospective study of ATC in Surveillance, Epidemiology and End Results (SEER) database. The association between LNM and survival of ATC was estimated by the Kaplan‐Meier method and Cox regression model. The predictive performances of the AJCC‐v8 and AJCC‐v7 were estimated through C‐index, Akaike information criterion (AIC) and Bayesian information criterion (BIC). Results A total of 313 patients with ATC were included in our analysis. Notably, LNM was identified as an independent risk factor for ATC mortality (adjusted HR, 1.47, 95% CI, 1.10–1.96; p = .009), while the risk of mortality in N1a group was comparable to that in N1b group according to univariate (HR, 1.30, 95% CI, 0.92–1.82; p = .133) and multivariate (adjusted HR 0.87, 95% CI, 0.60–1.27; p = .467) cox analyses. Applying the AJCC‐v8, the survival of migration population staged T1‐3aN1M0 was significantly worse than that of T1‐3aN0M0 patients (IVA stage), while was not different from that of T3b‐T4bN0/N1M0 patients (IVB stage). With a higher C‐index (0.60 vs. 0.59), lower AIC (2728 vs. 2732) and BIC (2732 vs. 2735), AJCC‐v8 was demonstrably a more favourable prediction model than AJCC‐v7. Conclusions This study demonstrated that LNM was independently associated with poor prognosis of ATC, and AJCC‐v8 with the modified staging of patients with LNM showed better survival predictive performance in ATC patients than AJCC‐v7.

Statistical evidence on breast cancer (BC) burden related to health and lifestyle risk factors are valuable for health policy-making. This study aimed to compare the trends in BC mortality and disability adjusted life years (DALYs) attributable to various health and life style risk factors among different world’s regions according to sociodemographic index (SDI). We extracted the age-standardized and age-specific rate of mortality and DALYs of women BC during 1990–2017 using the comparative risk assessment framework of the 2017 global burden of disease (GBD) study. We performed hierarchical age-period-cohort analysis to estimate age- and time-related trends, and effect of interactions between different risk factors on BC risk. During 1990–2017, the age-standardized rate of mortality and DALYs of women BC was increasing in less developed and under developing regions. The risk factor alcohol use [RR 51.3(95%CI 17.6–149.7)] and smoking [5.9(2.0–17.3)] were significantly highly contributor to increased mortality risk in high SDI region. Whereas in the low-SDI region, the greater mortality risk was observed in alcohol use [6.9(2.4–17)] and high FPG [2.7(1.5–3.1)]-related deaths. The adjusting for individual age, period, and risk factor effects, the significant interaction effect between metabolic risk factors and older ages were observed in all SDI regions and globally as well. However, an increasing cohort effect of alcohol, high fasting plasma glucose (FPG) and smoking-related death, and DALYs was observed during 1960 to 1985 cohorts among low-SDI regions. The age-standardized rates of mortality and DALYs due to BC has been increasing in low-SDI region. Alcohol consumption, high body mass index (BMI), high FPG, and smoking are potential BC risk factors particularly in older ages that leading to adverse disease outcomes. Therefore, rapid aging and prevalence of these prospective risk factors may strengthen the increasing mortality and DALYs of BC in low-SDI region. Hence, preventive measure along with strict action against concerned BC risk factors should be taken to reduce the disease burden specifically among lower-SDI regions.

Background The structure and composition of the gut microbiota influence patients’ response to therapeutic interventions. It is also known that the response to statin treatment can vary greatly from one patient to another, suggesting a possible connection between microbiome composition and response to statins. In the present study, we aim to explore the influence of the microbiome composition on the response to statin treatment among patients with coronary artery disease (CAD). Methods A prospective cohort of 836 CAD patients enrolled from January 2016 to December 2017 was used to perform a nested case-control study. We divided 110 CAD patients into two groups according to their response to statins (good response group and poor response group) and compared their gut microbiota. Results Our analysis reveals no significant difference in microbiome between the two groups. However, significant differences were found in the relative proportion of numerous genera between GR and PR groups. Most remarkably, we could observe that a poor response to statin treatment correlates to a significant decrease in the abundance of beneficial bacteria for the lipid metabolism (Akkermansia muciniphila (A. muciniphila) and Lactobacillus) and a significant increase in the abundance of bacteria (Holdemanella and Facecallibacterium). Conclusions Gut microbiota structure is associated with the response to statin. Our results suggest that manipulation of the gut microbiota composition can be an interesting and effective treatment strategy to blood lipid control among CAD patients.

Background Diabetes insipidus (DI) can be a common cause of polydipsia and polyuria. Here, we present a case of congenital nephrogenic diabetes insipidus (CNDI) accompanied with central diabetes insipidus (CDI) secondary to pituitary surgery. Case presentation A 24-year-old Chinese woman came to our hospital with the complaints of polydipsia and polyuria for 6 months. Six months ago, she was detected with pituitary apoplexy, and thereby getting pituitary surgery. However, the water deprivation test demonstrated no significant changes in urine volume and urine gravity in response to fluid depression or AVP administration. In addition, the genetic results confirmed a heterozygous mutation in arginine vasopressin receptor type 2 (AVPR2) genes. Conclusions She was considered with CNDI as well as acquired CDI secondary to pituitary surgery. She was given with hydrochlorothiazide (HCTZ) 25 mg twice a day as well as desmopressin (DDAVP, Minirin) 0.1 mg three times a day. There is no recurrence of polyuria or polydipsia observed for more than 6 months. It can be hard to consider AVPR2 mutation in female carriers, especially in those with subtle clinical presentation. Hence, direct detection of DNA sequencing with AVPR2 is a convenient and accurate method in CNDI diagnosis.

Background Cancer stem cell (CSC)-related chemoresistance leads to poor outcome of the patients with colorectal cancer (CRC). In this study, we identified the chemoresistance-relevant molecules and decipher the involved mechanisms to provide potential therapeutic target for CRC. We focused on Sec62, a novel target with significantly increased expression in chemoresistant CRC tissues, and further investigated its role in the progression of CRC. Methods Through analyzing the differentially-expressed genes between chemoresistant and chemosensitive CRCs, we selected Sec62 as a novel chemoresistance-related target in CRC. The expression and clinical significance of Sec62 were determined by immunoblotting and immunohistochemistry in tissues and cell lines of CRC. The roles of Sec62 in drug resistance, stemness and tumorigenesis were evaluated in vitro and in vivo using functional experiments. GST pull-down, western blot, coimmunoprecipitation and Me-RIP assays were performed to further explore the downstream molecular mechanisms. Results Sec62 upregulation was associated with the chemoresistance of CRC and poor outcome of CRC patients. Depletion of Sec62 sensitized CRC cells to chemotherapeutic drugs. Sec62 promoted the stemness of CRC cells through activating Wnt/β-catenin signaling. Mechanistically, Sec62 bound to β-catenin and inhibited the degradation of β-catenin. Sec62 competitively disrupted the interaction between β-catenin and APC to inhibit the β-catenin destruction complex assembly. Moreover, Sec62 expression was upregulated by the m6A-mediated stabilization of Sec62 mRNA. Conclusions Sec62 upregulated by the METTL3-mediated m6A modification promotes the stemness and chemoresistance of CRC by binding to β-catenin and enhancing Wnt signalling. Thus, m6A modification-Sec62-β-catenin molecular axis might act as therapeutic targets in improving treatment of CRC.

Myopia is the most common type of refractive errors characterized by excessive elongation of the ocular globe. With the increasing prevalence of myopia, improved knowledge of factors involved in myopia development is of particular importance. There are growing evidence suggesting that the choroid plays an important role in the regulation of eye growth and the development of myopia. Studies have demonstrated that thinning choroid is a structural feature of myopia, with a negative correlation between choroidal thickness and axial length, suggesting that the change in choroidal thickness may be a predictive biomarker for long-term changes in ocular elongation. Given the fact that the choroid is primarily a vascular structure capable of rapidly changing blood flow, variations of choroidal thickness might be primarily caused by changes in choroidal blood flow. Considering that hypoxia is associated with myopia and choroidal blood flow is the main source of oxygen and nourishment supply, apart from the effect on myopia possibly by changing choroidal thickness, decreasing choroidal blood flow may contribute to scleral ischaemia and hypoxia, resulting in alterations in the scleral structure and thus leading to myopia. This review aims to provide an overview of recent work exploring the influence of the choroid on myopia from perspectives of choroidal thickness and blood flow, which may present new predictive indicators for the onset of myopia and new targets for the development of novel therapeutic approaches for myopia.

To investigate the value of full-field digital mammography-based deep learning (DL) in predicting malignancy of Breast Imaging Reporting and Data System (BI-RADS) 4 microcalcifications. A total of 384 patients with 414 pathologically confirmed microcalcifications (221 malignant and 193 benign) were randomly allocated into the training, validation, and testing datasets (272/71/71 lesions) in this retrospective study. A combined DL model was developed incorporating mammography and clinical variables. Model performance was evaluated by using areas under the receiver operating characteristic curve (AUC) and compared with the clinical model, stand-alone DL image model, and BI-RADS approach. The predictive performance for malignancy was also compared between the combined model and human readers (2 juniors and 2 seniors). The combined DL model demonstrated favorable AUC, sensitivity, and specificity of 0.910, 85.3%, and 91.9% in predicting BI-RADS 4 malignant microcalcifications in the testing dataset, which outperformed the clinical model, DL image model, and BI-RADS with AUCs of 0.799, 0.841, and 0.804, respectively. The combined model achieved non-inferior performance as senior radiologists (p = 0.860, p = 0.800) and outperformed junior radiologists (p = 0.155, p = 0.029). The diagnostic performance of two junior radiologists was improved after artificial intelligence assistance with AUCs increased to 0.854 and 0.901 from 0.816 (p = 0.556) and 0.773 (p = 0.046), while the interobserver agreement was improved with a kappa value increased to 0.843 from 0.331. The combined deep learning model can improve the malignancy prediction of BI-RADS 4 microcalcifications in screening mammography and assist junior radiologists to achieve better performance, which can facilitate clinical decision-making. • The combined deep learning model demonstrated high diagnostic power, sensitivity, and specificity for predicting malignant BI-RADS 4 mammographic microcalcifications. • The combined model achieved similar performance with senior breast radiologists, while it outperformed junior breast radiologists. • Deep learning could improve the diagnostic performance of junior radiologists and facilitate clinical decision-making.

Acute lung injury (ALI) is the common and clinically severe complication. Dexmedetomidine (DEX) can protect against lipopolysaccharide (LPS)-induced ALI through anti-apoptosis, anti-inflammatory and immune regulatory actions. It is well documented that major causes of LPS-induced ALI are endoplasmic reticulum stress (ERS) and abnormally elevated CHOP. Moreover, XBP-1 can enhance CHOP expression. XBP-1S can aggravate ERS and XBP-1 U can repress ERS. By querying Starbase, miR-135a-5p interacts with XBP-1 and lncRNA MALAT1 sponges miR-135a-5p. It has been reported that MALAT1 interference markedly promoted the apoptosis of pulmonary microvascular endothelial cells in ALI rats by activating TLR4/NF-κB pathway. miR-135a-5p inhibitor remarkably alleviated LPS-induced A549 cell injury through suppressing cell apoptosis. In the present work, LPS was dripped into the nasal cavity of SD rats to establish the rat model of ALI and LPS was also applied to stimulate BEAS-2B cells to imitate ALI in vitro. Then, the pathology, lung function indexes, levels of inflammatory factors, apoptosis of lung tissues in SD rats and apoptotic level of BEAS-2B cells were measured, so as to confirm whether upregulation of lncRNA MALAT1 was able to suppress ERS, thus enhancing the protective effect of DEX against ALI. Herein, overexpression of lncRNA MALAT1 strengthened the remission effects of DEX on LPS-triggered ALI, severe pulmonary edema, inflammatory response and cell apoptosis of lung tissues in SD rats and reinforced the anti-apoptosis effect of DEX on LPS-stimulated BEAS-2B cells. Mechanically, lncRNA MALAT1 enhanced the protective effect of DEX against ALI by downregulating the ratio of XBP-1S/XBP-1U to repress ERS.

Introduction: Cardiovascular disease (CVD) is the leading cause of death and has caused a heavy burden in China. China has about 106 million CVD patients, including 33 million with stroke. This study presents the latest cardiovascular mortality in China in 2019 to provide evidence for disease control and prevention. Methods: Mortality data from the China Death Surveillance Point System (DSP System) was used for CVD mortality estimation. A descriptive analysis was conducted to demonstrate the results. Results: A total of 5.09 million CVD deaths were estimated in China in 2019, with a mortality rate and age-standardized mortality rate of 364.5 per 100,000 population and 276.0 per 100,000, respectively. Stroke is the leading cause of death, and the mortality rate and age-standardized mortality rate (ASMR) were 171.6 per 100,000 and 130.0 per 100,000, respectively. The second major cause was ischemic heart diseases, and the mortality rate and ASMR were 147.3 per 100,000 and 142.1 per 100,000, respectively. Stroke and ischemic heart diseases were the two major causes of CVD deaths, which accounted for over 87% of all CVD deaths. Conclusions: Although age-standardized mortality of CVD continues to decline in China, the number of deaths is still increasing. Therefore, prevention and control efforts for CVD should be maintained. In order to achieve the “Healthy China 2030” goal of reducing the mortality rate of CVD in China, it is necessary to further strengthen the prevention, control, and treatment capacity of stroke. Meanwhile, increases in ischemic heart disease deaths in highly developed areas should be monitored.

Both clinical observations and in vitro studies have confirmed that hyperoxaluria or hypercalciuria is one of the main factors that determine the phase formation of pathological calcium oxalate (Ca...

Introduction Age-related macular degeneration (AMD) is the main cause of visual impairment and the most important cause of blindness in older people. However, there is currently no effective treatment for this disease, so it is necessary to establish a risk model to predict AMD development. Methods This study included a total of 202 subjects, comprising 82 AMD patients and 120 control subjects. Sixty-six single-nucleotide polymorphisms (SNPs) were identified using the MassArray assay. Considering 14 independent clinical variables as well as SNPs, four predictive models were established in the training set and evaluated by the confusion matrix, area under the receiver operating characteristic (ROC) curve (AUROC). The difference distributions of the 14 independent clinical features between the AMD and control groups were tested using the chi-squared test. Age and diabetes were adjusted using logistic regression analysis and the “genomic-control” method was used for multiple testing correction. Results Three SNPs (rs10490924, OR = 1.686, genomic-control corrected p-value (GC) = 0.030; rs2338104, OR = 1.794, GC = 0.025 and rs1864163, OR = 2.125, GC = 0.038) were significant risk factors for AMD development. In the training set, four models obtained AUROC values above 0.72. Conclusions We believe machine learning tools will be useful for the early prediction of AMD and for the development of relevant intervention strategies.

Background Cancer is a complex heterogeneous disease to which singular modes of treatment mostly fail to produce a desired therapeutic efficacy. Targeting different cellular pathways using combinational therapies has been gaining popularity in cancer treatment, with the added benefit of reducing dosage and side effects. Methods A gold nanoparticle-mediated drug delivery nanoplatform was developed for co-delivery of doxorubicin and polo-like kinase 1 (PLK1) siRNA. Gold nanoparticles were coated with polyethyleneimine to facilitate assembly of PLK1 on the surface. Doxorubicin was loaded on nanoparticles through a pH-sensitive linker with a thiol group at one terminal end for controlled release. Results The therapeutic efficiency of this co-delivery system was evaluated in 2D and 3D cultured systems. The reduced IC50 value clearly demonstrated the synergistic effect of combined drug and gene delivery over their individual delivery in a cancer treatment model. Conclusion This study may provide an adaptable, facile platform to investigate drug-siRNA combinations for cancer inhibition.

Background In China, chronic obstructive pulmonary disease (COPD) was accounted for a quarter of the global COPD population and has become a large economic burden. However, the comprehensive picture of the COPD burden, which could inform health policy, is not readily available for all of the provinces of China. Here, we aimed to describe the burden of COPD in China, providing an up-to-date and comprehensive analysis at the national and provincial levels, and time trends from 1990 to 2019.Methods Following the methodology framework and general analytical strategies used in the GBD 2019, we analyzed the incidence, prevalence, mortality, and disability-adjusted life years (DALYs) attributable to COPD across China and the corresponding time trends from 1990 to 2019, stratified by age and province. We also presented the contribution of risk factors (e.g., smoking, ambient particulate matter, and occupational risks) to COPD-related mortality and DALYs. The association between COPD burden and socio-demographic index (SDI) were also evaluated. Results From 1990 to 2019, the incidence and prevalence of COPD increased by 61.2% and 67.8%, respectively, whereas the number of deaths and DALYs owing to COPD decreased. The age-standardized rates (ASRs) of COPD burden continuously decreased from 1990 to 2019. The crude rates of COPD burden dramatically increased with age and reached a peak in the older than 95 years age group. In 2019, the leading risk factor for COPD mortality and DALYs was tobacco use in the whole population, but ambient particulate matter pollution was the most significant risk factor in females. At the provincial level, the ASRs of COPD burden was significantly associated with the SDIs, with the highest ASRs in the western provinces with low SDIs. ConclusionsAlthough the ASRs of COPD burden in China substantially decreased at the national and provincial levels from 1990 to 2019, absolute numbers of COPD incidence and prevalence are still rising, indicating that COPD remains an important public health problem in China. Geographically targeted considerations should be developed to enhance COPD health and reduce the COPD burden throughout China and in specific provinces.

Exercise training benefits the heart. The knowledge of post-transcription regulation, especially RNA editing, in hearts remain rare. ADAR2 is an enzyme that edits adenosine to inosine nucleotides in double-stranded RNA, and RNA editing is associated with many human diseases. We found that ADAR2 was upregulated in hearts during exercise training. AAV9-mediated cardiac-specific ADAR2 overexpression attenuated acute myocardial infarction (AMI), MI remodeling, and doxorubicin (DOX)-induced cardiotoxicity. In vitro, overexpression of ADAR2 inhibited DOX-induced cardiomyocyte (CM) apoptosis. but it could also induce neonatal rat CM proliferation. Mechanistically, ADAR2 could regulate the abundance of mature miR-34a in CMs. Regulations of miR-34a or its target genes (Sirt1, Cyclin D1, and Bcl2) could affect the pro-proliferation and anti-apoptosis effects of ADAR2 on CMs. These data demonstrated that exercise-induced ADAR2 protects the heart from MI and DOX-induced cardiotoxicity. Our work suggests that ADAR2 overexpression or a post-transcriptional associated RNA editing via ADAR2 may be a promising therapeutic strategy for heart diseases.

Cardiovascular-related diseases continue to be a leading cause of death globally. Among ischemic-induced cardiac diseases, myocardial infarction (MI) is reported to be of an alarming value. Despite numerous improvements in the medical intrusions, still this armamentarium fails to be effective in managing the illness without setbacks. Ferruginol (FGL) is a major polyphenols and terpenoids with numerous pharmacological activities including antioxidant and anti-inflammatory. Following, this work was aimed to explore the cardio protective effect of FGL (50 mg/kg) in isoprenaline hydrochloride (ISO)-induced MI in experimental rats. After treatment with FGL in ISO-induced MI in rats, noticeable changes were observed in the experimental rats. Injection of ISO to rats resulted in the augmented cardiac weight, serum cardiac markers (creatine kinase, creatine kinase-MB, cardiac troponin T, and Cardiac troponin I), lipid peroxidation end products (thiobarbituric acid-reactive substance and lipid hydroperoxides), reduced endogenous antioxidants (superoxide dismutase, catalase, glutathione peroxidase, and glutathione), reduced ATPase activity, and escalated pro-inflammatory cytokines (interleukin-6, tumor necrosis factor-α, and nuclear factor-κB) levels. Interestingly, the FGL supplementation to the ISO-treated rats revealed the diminished heart weight, reduced cardiac markers, and lipid peroxidation. FGL also possessed the improved antioxidants status and diminished pro-inflammatory mediator levels. The outcomes of histological analysis also evidenced the cardio protective role of FGL. Treatment with FGL reduced the cardiac damage biomarkers maintained to near normal levels in ISO-induced rats. These study findings disclose the prospective capability of FGL in the treatment of MI in the future.

With obesity rate consistently increasing, a strong relationship between obesity and fatty liver disease has been discovered. More than 90% of bariatric surgery patients also have non-alcoholic fatty liver diseases (NAFLDs). NAFLD and non-alcoholic steatohepatitis (NASH), which are the hepatic manifestations of metabolic syndrome, can lead to liver carcinogenesis. Unfortunately, there is no effective medicine that can be used to treat NASH or liver cancer. Thus, it is critically important to understand the mechanism underlying the development of these diseases. Extensive evidence suggests that microRNA 22 (miR-22) can be a diagnostic marker for liver diseases as well as a treatment target. This review paper focuses on the roles of miR-22 in metabolism, steatosis, and liver carcinogenesis. Literature search is limited based on the publications included in the PubMed database in the recent 10 years.

To elucidate the sleep quality characteristics and factors related to either good or poor sleep quality in acromegaly patients before surgery and to explore sleep quality changes after transsphenoidal surgery and the factors related to these changes.We prospectively enrolled 39 acromegaly patients and 78 patients with nonfunctioning pituitary adenomas. Scales for anxiety, depression, disease stigma and nasal condition were evaluated. The Pittsburgh Sleep Quality Index (PSQI) questionnaire was administered before surgery as well as one month and three months after surgery.A higher percentage of acromegaly patients had poor sleep quality compared to controls (35.9% vs. 5.1%, p 0.001). In addition, acromegaly patients experienced worse subjective sleep quality, extended sleep latency, increased sleep disturbance and decreased daytime functioning. Higher scores for anxiety, disease stigma and sinonasal outcomes were correlated with worse sleep quality in acromegaly patients. At one month after transsphenoidal surgery, we found worse subjective sleep quality, extended sleep latency, shortened sleep duration, impaired sleep efficiency and increased sleep disturbance in acromegaly patients. At three months postoperatively, most impaired PSQI domains in acromegaly patients recovered to preoperative levels. The use of soluble gauze was related to decreased sleep quality at one month after surgery and severe anxiety and depression were related to improved sleep quality at three months after surgery.Sleep quality was reduced in acromegaly patients. Moreover, sleep quality initially worsened after surgery but later recovered. Emotional problems and the use of soluble gauze were related factors.None.

Aim To evaluate the intraocular pressure (IOP)-lowering efficacy and safety of tafluprost 0.0015% eye drops [benzalkonium chloride (BAK) 0.1 mg/mL] compared with that of latanoprost 0.005% eye drops (BAK 0.2 mg/mL) for primary open angle glaucoma (POAG) and ocular hypertension (OHT). Methods All the randomized controlled trials (RCTs) about treating POAG and OHT comparing tafluprost and latanoprost were collected by searching PubMed, Embase, Cochrane Library, CNKI and VIP. The outcomes of interest to evaluate the clinical efficacy and adverse effects included IOP and patient-related drop discomfort. Results Five RCTs involving 888 glaucoma patients were included. The results showed that, 1) at the end of the study, no statistically significant differences were observed in IOP reduction [standard mean difference (SMD) =0.48, 95%CI 0.07 to 0.88, P=0.085] between tafluprost and latanoprost; 2) No statistically significant differences were observed in adverse events of foreign-body sensation [relative risk (RR) =0.62, 95%CI 0.26 to 1.46, P=0.269], eye irritation (RR=1.16, 95%CI 0.49 to 2.75, P=0.744), eye pain (RR=2.000, 95%CI 0.949 to 4.216, P=0.07), iris hyper-pigmentation (RR=0.741, 95%CI 0.235 to 2.334, P=0.61), dry eye (RR=1.154, 95%CI 0.409 to 3.256, P=0.79) and eye pruritus (RR=1.600, 95%CI 0.536 to 4.774, P=0.4) between tafluprost and latanoprost. However, tafluprost showed more reported incidence of conjunctival hyperaemia than latanoprost (RR=2.11, 95%CI 1.24 to 3.59, P=0.006). Conclusion Tafluprost 0.0015% eye drops (BAK 0.1 mg/mL) and latanoprost 0.005% eye drops (BAK 0.2 mg/mL) are comparable in lowering IOP for open angle glaucoma (OAG) and OHT. It does not differ in the incidence of foreign-body sensation, eye irritation, eye pain, iris hyper-pigmentation, dry eye and eye pruritus, but tafluprost shows less ocular tolerability because of more incidence of conjunctival hyperaemia.

Staphylococcus epidermidis is one of the main causes of medical device-related infections and bovine mastitis owing to its biofilm-forming abilities. Oxytropis glabra DC. is one of the most widespread Fabaceae species and used as a Chinese herbal formulation in Western China. Our research investigated the effects of O. glabra on the biofilm formation of S. epidermidis and the possible inhibiting mechanism. The biofilm-forming reference strain, S. epidermidis SE-1 (ATCC 35,984), was employed as a model and semi-quantitative biofilm assay was performed to evaluate the antibiofilm activity of O. glabra. The exopolysaccharides (EPS) production and expression of ica operon were studied to explore the possible antibiofilm mechanism using thin-layer chromatography and quantitative real-time PCR assay, respectively. The results obtained indicated that O. glabra decoction at 7.5 mg mL−1 significantly inhibited biofilm formation by about 95% without affecting cell growth of S. epidermidis. Two hydrolysis productions of EPS were significantly decreased by 64% and 54% with the addition of 7.5 mg mL−1O. glabra and the expression of icaR was significantly up-regulated 2.2-times, whereas icaB was significantly down-regulated more than 50% by 7.5 mg mL−1O. glabra. These findings suggest a potential application for O. glabra as a promising candidate for the exploration of new drugs against S. epidermidis biofilm-associated infections.

PTP1B is a key negative regulator of insulin signaling transduction, and the inhibition of PTP1B has emerged as a potential therapeutic strategy to treat T2DM. 3,4-Dibromo-5-(2-bromo-6-(ethoxymethyl)-3,4-dihydroxybenzyl)benzene-1,2-diol (BPN), a natural bromophenol isolated from marine red alga Rhodomela confervoides, was found to inhibit PTP1B activity in our previous study. Herein, we identified that BPN functioned as a competitive PTP1B inhibitor and enhanced phosphorylation of IRβ, IRS-1 and Akt in palmitate acid-induced insulin-resistant HepG2 cells. Moreover, 2-deoxyglucose uptake technology-based characterization demonstrated that BPN could stimulate glucose uptake in HepG2 cells. Furthermore, the effects of BPN against oxidative stress were investigated and showed that BPN attenuated oxidative stress by attenuating ROS generation. Finally, long-term oral administration of BPN at dose of 20 mg kg−1 significantly reduced blood glucose levels in streptozotocin-induced diabetic mice and no visible toxic effects were observed. Our work is thus expected to provide a natural uncharged PTP1B inhibitor that could be used as a potential lead compound for further research.

IntroductionCancer is an important public health concern with heavy disease burden in China. In 2017, cancer is the leading cause of death, with around 2.60 million deaths, which accounts for 26.07% of all deaths. This study aims to present cancer mortality in China in 2018 to provide evidence for cancer control and prevention. MethodsMortality data from China Cause of Death Reporting System (CDRS) and population data from National Bureau of Statistics are used for cancer mortality estimation. A descriptive analysis was conducted to demonstrate the results. ResultsA total of 2,557,297 cancer deaths were estimated in China in 2018 with a mortality rate and age-standardized mortality rate of 183.89 and 145.60 per 100,000, respectively. Lung, liver, and stomach cancer were the three leading causes of cancer death and accounted for around 56.75% of all cancer deaths. The age-standardized mortality rate was higher in men (194.37 per 100,000) than in women (99.47 per 100,000), in urban areas (148.25 per 100,000) than in rural areas (144.62 per 100,000), and in eastern regions (150.57 per 100,000) than in central (142.09 per 100,000)/western regions (141.54 per 100,000). The age-specific mortality rate remains low for the population younger than 44 years old and reaches its peak after 80 years old. Leukemia is the leading cause of cancer death among those aged 0–14 years in both sexes, while breast cancer is the leading cause of cancer death in women aged 15–44 years. Conclusions and Implications for Public Health PracticeThe cancer mortality patterns show substantial disparities among sexes, age groups, areas, and regions. Healthy lifestyle promotion, active vaccination uptake, and environmental governance are essential to eliminate cancer-related risk factors in the overall population. Tailored strategies for the early screening and diagnosis, therapeutic management, and palliative care should be a top priority for enforcement among target populations and regions.

Background: This study aimed to investigate the association of circular RNA itchy E3 ubiquitin protein ligase (circ-ITCH) expression with disease risk, clinical characteristics, progression-free survival (PFS) and overall survival (OS) of multiple myeloma (MM), and to explore the influence of circ-ITCH overexpression on MM cell activities n vitro . Methods: Bone marrow samples from 92 MM patients and 30 healthy controls were collected, and circ- ITCH expression was detected by quantitative polymerase chain reaction. PFS and OS in MM patients were calculated. Circ-ITCH in human MM cell lines and normal bone marrow mononuclear cells (BMMCs) were detected. Circ-ITCH overexpression and control overexpression plasmids were transfected to U226 cell line, and cell proliferation as well as apoptosis were assessed. Results: Circ-ITCH expression was under-expressed in MM patients compared to healthy controls. And receiver operating characteristic curve displayed that circ-ITCH could distinguish MM patients from healthy controls [area under curve: 0.809 (95% CI: 0.722–0.895)]. Additionally, circ-ITCH high expression was associated with decreased International Staging System (ISS) stage in MM patients. Kaplan-Meier curves and Cox’s regression analysis displayed that circ-ITCH expression was positively correlated with PFS and OS. In vitro , circ-ITCH expression was lower in MM cell lines (including RPMI8226, U226 and NCI-H929) compared to normal BMMCs. In U226 cells, cell proliferation was decreased but apoptosis was elevated by circ-ITCH overexpression. Conclusions: Circ-ITCH might serve as a potential biomarker and treatment target for MM.

Background and aims Bile acids play important roles in lipid metabolism. Several studies have found that patients with coronary artery disease (CAD) have lower bile acid fecal excretion compared to individuals without CAD. However, few studies have focused on the roles of more accessible serum total bile acids (TBA) in the progression of CAD. The aim of this study was to explore the potential relationship between fasting serum TBA and the presence of CAD, myocardial infarction (MI) and severity of coronary lesions. Methods A total of 7438 consecutive patients with suspected CAD, who had undergone coronary angiography, were enrolled. The severity of coronary lesions was evaluated using the Gensini score (GS). The relationships between fasting serum TBA and the presence and severity of CAD were evaluated. Results CAD patients had lower serum TBA than individuals without CAD, and patients with MI had lower TBA than those without CAD. Spline analyses showed an L-shaped relationship of the fasting serum TBA with the presence and severity of CAD, and the breakpoint approximated the normal upper limit (10 μmol/L). A lower TBA concentration (less than the median 3.6 μmol/L) was independently and significantly associated with the presence and severity of CAD, especially for the presence of MI (odds ratios 2.04, 95% confidence interval (1.71–2.44), C-index 0.9269). Conclusions Fasting serum TBA level is highly associated with the presence and severity of CAD in patients undergoing coronary angiography for suspected CAD.

Background Aerobic vaginitis (AV) is a newly defined type of bacterial vaginitis, but its pathogenesis is not yet clear. Streptococcus anginosus appears as an emerging pathogen in recent case reports, and colonizes in vagina of patients with AV. In this study, we investigate the pathogenesis of S. anginosus in AV. Materials and methods (1) We collected 41 vaginal specimens from 21 healthy, fertile women with normal vaginal flora (NM), 10 with bacterial vaginosis (BV) and 10 with AV; their microbiome structure was analysed by 16S rRNA gene sequencing. (2) S. anginosus and vaginal epithelial cells were cocultured in vitro, and cytotoxicity was tested by an LDH kit. (3) The S. anginosus virulence gene sag was knocked out, and the cytotoxicity of the mutant in vaginal epithelial cells was tested. Results (1) The microbiome structure of AV was dramatically different from that of BV and NM. The predominant genera of the three groups were Streptococcus spp., Gardnerella spp. and Lactobacillus spp. Streptococcus spp. were significantly more abundant in AV than in BV (95% CI [0.1391, 0.8676], P

BACKGROUND: Bevacizumab is a monoclonal antibody (mAb) against vascular endothelial growth factor (VEGF) and used for treatments of various cancers. Due to the high costs of bevacizumab treatments, a biosimilar provides an affordable alternative therapy for cancer patients. METHODS: In this randomized, double-blind, multicenter, phase 3 study, locally advanced, metastatic or recurrent non-squamous non-small cell lung cancer (NSCLC) patients with wild-type epidermal growth factor receptor were enrolled and randomized (1:1) into IBI305 or bevacizumab groups. Patients received 6 cycles of paclitaxel/carboplatin plus IBI305 or bevacizumab 15 mg/kg intravenously followed by IBI305 or bevacizumab 7.5 mg/kg maintenance until disease progression, unacceptable toxicity or death. The primary endpoint was confirmed objective response rate (ORR) by an independent radiological review committee (IRRC) and secondary endpoints included disease control rate (DCR), progression-free survival (PFS), duration of response (DOR), overall survival (OS) and safety. RESULTS: A total of 450 NSCLC patients were enrolled (224 in IBI305 group and 226 in bevacizumab group). ORRs were 44.3% for IBI305 and 46.4% for bevacizumab, and the ORR ratio was 0.95 (90% CI: 0.803 to 1.135), within the predefined equivalence margin of 0.75 to 1.33. No significant difference in PFS (7.64 vs. 7.77 m, P=0.9987) was observed between the 2 groups. Serious adverse events (AEs) occurred in 33.5% (75/224) of patients in the IBI305 group and 37.6% (85/226) in the bevacizumab group. AEs ≥ grade 3 were similar in the IBI305 and bevacizumab groups [84.4% (189/224) vs. 89.8% (203/226), P=0.085]. CONCLUSIONS: IBI305 is similar to bevacizumab in terms of efficacy and safety. TRIAL REGISTRATION: Clinicaltrials.org Identifier: NCT02954172. Registered on 3 November 2016. Https://clinicaltrials.gov/.

INTRODUCTION We aimed to evaluate the clinical performance of early administration of recombinant human B-type natriuretic peptide (rhBNP) to ST-elevation myocardial infarction (STEMI) patients receiving percutaneous coronary intervention (PCI) treatment. METHODS In total, 185 patients diagnosed with STEMI were enrolled and randomised into either the placebo-treated (n = 88) or rhBNP-treated (n = 97) group. Patients were given either saline or rhBNP ten minutes before PCI and monitored with various cardiac parameters, including accelerated idioventricular rhythm, frequent ventricular premature beat (FVPB), ventricular tachycardia, systolic blood pressure, thrombolysis in myocardial infarction (TIMI) 3 gradation, corrected TIMI frame count (cTFC) and myocardial blush grade (MBG) 3 classification. RESULTS Our results revealed no difference in accelerated idioventricular rhythm between the two groups. However, FVPB and ventricular tachycardia were significantly decreased in rhBNP-treated patients compared to placebo-treated patients (p < 0.05). Moreover, the occurrence ratio of reperfusion-associated low blood pressure in rhBNP-treated patients was lower than in placebo-treated patients (p = 0.03), while no difference was observed in infarction-related arteries TIMI 3 blood flow between the two groups (p = 0.23). Importantly, measurement of post-reperfusion blood flow velocity via cTFC suggested that rhBNP treatment could significantly increase blood circulation (p = 0.003). After stent implantation, the acquisition rate of MBG 3 was higher in rhBNP-treated patients compared to placebo-treated patients (p = 0.071), although the difference was not significant. CONCLUSION We concluded that early administration of rhBNP can ameliorate the severity of reperfusion injury for STEMI patients receiving PCI treatment.

BACKGROUND Worldwide, head and neck cancers are the eighth most common malignancy. Single nucleotide polymorphisms (SNPs) are associated with susceptibility to cancer and sensitivity to radiotherapy and chemotherapy. The inflammatory cytokine, transforming growth factor-ß1 (TGF-ß1), is involved in the progression of malignancy. This study aimed to systematically review the literature and undertake a meta-analysis of case-control studies on the association between 869T/C, 509C/T, and 915G/C polymorphisms of the TGF-ß1 gene and head and neck cancers. MATERIAL AND METHODS The published literature in the English and Chinese languages were searched to identify relevant studies reporting TGF-ß1 gene polymorphisms and head and neck cancer. The PubMed, Embase, Wanfang Data, and CNKI databases were searched. Data were extracted from eligible studies, and meta-analysis was performed using Stata version 12.0 software. RESULTS Ten case-control studies were identified. There was a significant association between the 869T/C polymorphism of the TGF-ß1 gene and susceptibility to head and neck cancer. Subgroup analysis showed that the 869T/C polymorphism was not significantly associated with the histological type of head and neck cancer, but was significantly associated with susceptibility to head and neck cancer in the Asian population. The 509C/T polymorphism of the TGF-ß1 gene was not significantly associated with susceptibility to nasopharyngeal cancer (NPC), but the 915G/C polymorphism was associated with susceptibility to oral cancer. CONCLUSIONS Data from this meta-analysis showed that the 869T/C and 915G/C polymorphisms of the TGF-ß1 gene might be associated with susceptibility to head and neck cancer.

Background : This study aimed to identify changing spatial and temporal trends of lung cancer mortality rates (LCMRs) among subpopulations in China (according to region, age, and sex). Methods : Data on LCMRs from 2006 to 2015 were extracted from the Chinese National Death Surveillance. Joinpoint regression and seasonal decomposition were used to assess the temporal trends. A geographic information system and spatial kriging interpolation were used to examine the spatial trends. Results : LCMRs in men aged 30 to 49 years significantly declined nationally from 2009 to 2015 (annual percentage change, –2.7%; P < .05), but they continued to rise in men aged ≥ 70 years and women aged ≥ 50 years in the east, people aged 50 to 69 years in the south, and most groups in the southwest. Among provincial capital cities, Shenyang, Changsha, and Hohhot had the highest 10-year average LCMR for men aged 30 to 49 years, 50 to 69 years, and ≥ 70 years, respectively; among all ages of women, Harbin had the highest average LCMR. Over the 10 years, the odds of the increases in LCMRs in men and women aged 30 to 69 years decreased by 3% to 7% with the longitudes or latitudes increasing by 1° (ORs ranged from 0.93 [95% CI, 0.90-0.95) to 0.97 [95% CI, 0.95-0.99]). Conclusions : Disparities in the spatial and temporal trends of LCMRs among subpopulations highlight the need for investigation into potential drivers, especially for the east, south, and southwest of China. These findings may help health authorities target interventions to those most in need to reduce the lung cancer burden in China.

Several studies have demonstrated that allergic asthma can induce atherosclerosis formation in mice. Moreover, allergic asthma and atherosclerosis have been shown to be strongly associated with dyslipidemia. In this study, we investigated the underlying mechanism of allergic asthma-aggravated atherosclerosis-induced cholesterol metabolism disorder in asthmatic apoE-/- mice. We found that allergic asthma increased the expression of 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) in the liver and CD36 in the aorta during the acute and advanced stages of atherosclerosis, respectively. These results indicate that cholesterol biosynthesis is increased during acute atherosclerosis and cholesterol uptake and foam cell formation is increased during advanced atherosclerosis. Simvastatin administration significantly ameliorated the aortic root lesion size of asthmatic mice and significantly decreased HMGCR and CD36 expression. However, the expression of the low-density lipoprotein receptor and ATP-binding cassette transporter A1 was markedly increased, indicating that the beneficial effect of statins in allergic asthma and coronary artery disease was mediated, at least in part, by decreasing cholesterol biosynthesis and foam cell formation. In conclusion, allergic asthma aggravates atherosclerosis by regulating cholesterol metabolism in apoE-/- mice. Allergic asthma selectively promotes cholesterol biosynthesis in acute atherosclerosis and increases foam cell formation in advanced atherosclerosis.

Atmospheric particulate matter (PM2.5 and PM10) samples were collected at urban and suburban sites in Xi'an City from December 2016 to November 2017. Sixteen priority polycyclic aromatic hydrocarbons (PAHs) associated with PM2.5 and PM10 were analyzed for their seasonal variations, sources, health risks, and influencing factors. The results showed that the annual average concentrations of PM2.5 and PM10 were 111 and 185 μg/m3, respectively, exceeding the National Ambient Air Quality Standard of China (35 μg/m3 for PM2.5 and 70 μg/m3 for PM10 in Grade II). The annual averages of PM2.5- and PM10-bound total PAHs were 63.1 and 66.8 ng/m3, respectively, with a PM2.5 decrease in the order of winter (115 ng/m3) > > spring (47.6 ng/m3) > summer (33.2 ng/m3) > autumn (30.8 ng/m3) and a PM10 decrease in the order of winter (127 ng/m3) > > spring (55.6 ng/m3) > autumn (32.6 ng/m3) > summer (30.2 ng/m3). The most abundant PAHs were benzo[a]anthracene, benzo[b]fluoranthene, and fluoranthene. The PM2.5- and PM10-bound PAHs were originated mainly from traffic emissions (51.0% and 43.4%), followed by combustion of biomass (20.4% and 23.6%) and coal (16.8% and 23.1%). Pressure and relative humidity were positively correlated with PM2.5 and PM10 as well as PM2.5- and PM10-bound PAHs, while temperature, visibility and wind speed had negative correlations. The annual means of TEQs (toxic equivalency quantities) for the 16 PAHs in PM2.5 and PM10 were 10.1 and 10.2 ng/m3, respectively, being attributed to 7 carcinogenic PAHs (> 95%). The ECRs (lifetime excess cancer risks) for PM2.5- and PM10-bound PAHs were 1.12 × 10−3 and 1.17 × 10−3, i.e., 1125 and 1169 lung cancer cases per million, respectively. The ILCRs (incremental lifetime cancer risks) due to PM2.5- and PM10-bound PAHs for adults (1.21 × 10−6 and 1.26 × 10−6) were larger than those for children (2.09 × 10−7 and 2.17 × 10−7), with acceptable carcinogenic risks. The ambient levels of PM and most PM-bound PAHs as well as their TEQs, ECRs and ILCRs exhibited a spatial pattern of the suburban site > the urban site and a seasonality with winter and spring > summer and autumn. The results suggest that it is important to control PM2.5 and PM10 for local air quality improvement and special attention should be paid to PM and PM-bound PAHs in suburban areas, particularly in winter and spring.

Background Kawasaki disease (KD) is an acute febrile vasculitis that often occurs in children under 5 years. Ptosis and muscle weakness associated with KD are rarely documented. Case presentation We present a case of KD with eyelid ptosis and muscle weakness in a 3-year-old boy. At admission, grade IV and grade III muscle strength were recorded for upper and lower limbs, respectively. Diminished patellar tendon reflex was noted. Laboratory evaluation showed hypokalemia with the serum potassium concentration of 2.62 mmol/L. Intravenous immunoglobulin (IVIG) and aspirin were initiated immediately accompanied with methylprednisolone for adjunctive therapy. Potassium supplement was administered at the same time, which resulted in the correction of hypokalemia on the 2nd day of admission but no improvement in ptosis and muscle weakness. Neostigmine testing, lumber puncture, electromyography, and cerebral and full spine MRI were performed, which, however, did not find evidence for neural and muscle diseases. On the 5th day, the fever was resolved. On the 6th day, eyelid ptosis disappeared. And on the 14th day, the muscle strength and muscle tension returned to normal, patellar tendon reflex could be drawn out normally, and the boy regained full ambulatory ability. Conclusions KD might affect the neural and muscular systems, and KD complicated with eyelid ptosis and muscle weakness is responsive to the standard anti-inflammatory treatment plus adjunctive corticosteroid therapy.

BackgroundCigarette smoking is associated with nasopharyngeal cancer (NPC) risk. Whether quitting reduces the risk is unclear. We investigated the associations of NPC with duration of and age at quitting in an endemic region.MethodsWe investigated the associations between NPC and quitting in a multicenter case-control study in Hong Kong with 676 newly diagnosed NPC cases and 1,285 hospital controls between 2014 and 2017, using a computer-assisted self-administered questionnaire. Multivariable unconditional logistic regression yielded adjusted odds ratios (AORs) of NPC by quitting status, duration and age of quitting, combinations of duration and age of quitting, and quitting to smoking duration ratio, compared with current smoking.ResultsQuitting (AOR: 0.72; 95% CI: 0.53–0.98) and never smoking (0.73, 0.56–0.95) were associated with lower NPC risk. NPC risk decreased with (i) longer quitting duration (p < 0.01), reaching significance after 11–20 (0.62, 0.39–0.99) and 21+ years (0.54, 0.31–0.92) of quitting; (ii) younger quitting age (p = 0.01), reaching significance for quitting at p < 0.01), reaching significance when the ratio reached 1 (0.60, 0.39–0.93). Quitting younger (age ConclusionsWe have shown longer duration and younger age of quitting were associated with lower NPC risk, with dose-response relations. Our findings support including smoking as a cause of NPC. Stronger tobacco control measures and quitting services are needed to prevent NPC.

Wei Liu,&ast; Wei Wang,&ast; Jiangmei Liu, Yunning Liu, Shidi Meng, Feixue Wang, Zheng Long, Jinlei Qi, Jinling You, Lin Lin, Lijun Wang, Maigeng Zhou, Peng Yin National Center for Chronic and Noncommunicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Peng YinNational Center for Chronic and Noncommunicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, No. 27 Nanwei Road, Beijing, 100050, People’s Republic of ChinaTel +86 010-63015058Email yinpeng@ncncd.chinacdc.cnBackground: To examine trends in chronic obstructive pulmonary disease (COPD) mortality and years of life lost (YLL) due to COPD for all provinces in China during 2005– 2020.Methods: Data for COPD mortality were derived from China National Mortality Surveillance System (NMSS). We analyzed the numbers and age-standardized rates of death and YLL due to COPD in China, during 2005– 2020. We carried out decomposition analysis to analyze the drivers of change in COPD deaths during the study period.Results: The age-standardized mortality rate of COPD in China decreased significantly from 99.5/100,000 in 2005 to 50.5/100,000 in 2020. Similar trend was seen in the age-standardized YLL rate. The mortality rate increased with age. During 2005– 2020, the age-standardized mortality rate decreased in all provinces (except for Tibet) with the largest decline in Jilin (− 77.8%), Henan (− 68.4%) and Fujian (− 67.1%). The decreased number of deaths was decomposed as population growth (8.5%) and population ageing (69.7%) with offset by decline of age-specific mortality (− 87.5%).Conclusion: COPD remains an important public health problem in China, though significant reductions of COPD mortality and YLL rate were observed. Vigorous prevention and control strategies should be enhanced to improve the quality of life of COPD patients and reduce the premature death caused by COPD in Chinese population.Keywords: COPD, mortality, YLL

Background: Diabetic cardiomyopathy is the primary complication associated with diabetes mellitus and also is a major cause of death and disability. Limited pharmacological therapies are available for diabetic cardiomyopathy. Qiliqiangxin (QLQX), a Chinese medication, has been proven to be beneficial for heart failure patients. However, the role and the underlying protective mechanisms of QLQX in diabetic cardiomyopathy remain largely unexplored.Methods: Primary neonatal rat cardiomyocytes (NRCMs) were treated with glucose (HG, 40 mM) to establish the hyperglycemia-induced apoptosis model in vitro. Streptozotocin (STZ, 50 mg/kg/day for 5 consecutive days) was intraperitoneally injected into mice to establish the diabetic cardiomyopathy model in vivo. Various analyses including qRT-PCR, western blot, immunofluorescence [terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) staining] histology (hematoxylin–eosin and Masson's trichrome staining), and cardiac function (echocardiography) were performed in these mice. QLQX (0.5 μg/ml in vitro and 0.5 g/kg/day in vivo) was used in this study.Results: QLQX attenuated hyperglycemia-induced cardiomyocyte apoptosis via activating peroxisome proliferation-activated receptor γ (PPARγ). In vivo, QLQX treatment protected mice against STZ-induced cardiac dysfunction and pathological remodeling.Conclusions: QLQX attenuates diabetic cardiomyopathy via activating PPARγ.

Global DNA hypomethylation has been reported in patients with chronic hepatitis B (CHB) and non-alcoholic fatty-liver disease (NAFLD). However, the global DNA methylation profile of patients with concurrent NAFLD and CHB (NAFLD + CHB) is still unclear. We aimed to detect the hepatic global DNA methylation levels of NAFLD + CHB patients and assess the associated risk factors. Liver biopsies were collected from 55 NAFLD patients with or without CHB. The histological characteristics of the biopsy were then assessed. Hepatic global DNA methylation levels were quantified by fluorometric method. The hepatic global DNA methylation levels in NAFLD + CHB group were significantly lower than that in NAFLD group. Participants with fibrosis showed lower levels of hepatic global DNA methylation than those without fibrosis. Participants with both CHB and fibrosis had lower levels of hepatic global DNA methylation than those without either CHB or fibrosis. The co-occurrence of CHB and fibrosis was significantly associated with a reduction in global DNA methylation levels compared to the absence of both CHB and fibrosis. Our study suggests that patients with NAFLD + CHB exhibited lower levels of global DNA methylation than patients who had NAFLD alone. The co-occurrence of CHB and liver fibrosis in NAFLD patients was associated with a decrease in global DNA methylation levels.

Mental retardation-40 (MRD40) is a rare autosomal dominant neurodevelopmental disorder with a poor prognosis that is caused by a heterozygous mutation in chromosome alignment maintaining phosphoprotein 1 (CHAMP1). It was previously considered a non-syndromic disease due to the lack of specific external features. Only limited international reports describing CHAMP1 mutations are currently available. The present case study was the first to report on a Chinese patient with MRD40. The patient presented with severe global development delay with significant craniofacial dysmorphia. Using trio whole-exome sequencing, a novel de novo frameshift mutation in CHAMP1, NM_032436.2: c.530delCinsTTT, was identified, which expands the spectrum of the known pathogenic variants. The present case report helps to improve the syndromic profile of the rare MRD40 disorder and provides an example for the clinical diagnosis of MRD40.