Epidemiology and molecular characterization of carbapenem-resistant Klebsiella pneumoniae isolated from neonatal intensive care units in General Hospital of Ningxia Medical University, China, 2017-2021.

OBJECTIVES: This study aimed to retrospectively investigate the epidemiology and molecular characteristics of carbapenem-resistant Klebsiella pneumoniae (CRKP) isolates from neonatal intensive care units (NICU) between 2017 and 2021. METHODS: The antibacterial susceptibility of all strains was assessed using the VITEK 2 compact system. The presence of antibiotic resistance, virulence genes, sequence types (STs), capsular (K) types, and the wzi genes was determined through polymerase chain reaction (PCR). Molecular typing was performed by pulsed-field gel electrophoresis (PFGE) using the restriction enzyme XbaI. Additionally, the virulence potential of peg344-positive strains was evaluated using the string test and mouse intraperitoneal infection models. Whole-genome sequencing was conducted on the DNB system and PacBio platforms. RESULTS: A total of 46 CRKP isolates were collected during the study period. Out of these, 93.47% (43/46) were identified as CRKP strains belonging to the ST76-K10 type carrying blaNDM-5. It was observed that CRKP infection resulted in more severe clinical symptoms compared to CRKP colonization. Among the CRKP strains, a hypervirulent CRKP strain called KP-63, belonging to the ST23 type, was identified. This strain exhibited high mortality in the mouse infection model and was found to possess virulence genes. Genomic alignment analysis revealed a significant similarity between the virulence plasmid from KP-63 strain (pKP-63) and pK2044 from the hypervirulent K. pneumoniae strain NTUH-2044. CONCLUSIONS: There has been a potential dissemination of ST76-K10 type CRKP carrying blaNDM-5 in the NICU at Ningxia Hospital. Neonatal CRKP infection has been found to cause more severe clinical symptoms than colonization. Furthermore, we have discovered a CR-hvKP strain of ST23 with serotype K1, which exhibits a significant resemblance in its virulent plasmid to pK2044. Therefore, it is crucial to enforce effective measures to restrict the spread and hinder the evolution of CRKP within the hospital.

Determination of trace chelating carboxylic acids in rice by green extraction combined with liquid chromatography-mass spectrometry analysis and its application in the evaluation of old and new rice.

RATIONALE: Accurate identification of old rice samples from new ones benefits their market circulation and consumers. However, the current detection methods are still not satisfactory because of their insufficient accuracy or (and) time-consuming process. METHODS: Chelating carboxylic acids (CCAs) were selectively extracted from rice, by stirring with chelating resin and a dilute Na2CO3 solution. The green analytical chemistry guidelines for sample preparation were investigated by using the green chemistry calculator AGREE prep. The extractant was determined by liquid chromatography-mass spectrometry (LC/MS), and statistical analysis of the analytical data was carried out to evaluate the significance of the difference by ChiPlot. RESULTS: The limit of quantitation for the CCAs is in the range of 1 to 50 ng/mL, with a reasonable reproducibility. The CCAs in 23 rice samples were determined within a wide concentration range from 0.03 to 1174 µg/g. Intriguingly, the content of citric acid, malonic acid, α-ketoglutaric acid and cis-aconite acid in new rice was each found to be distinctively higher than that in old rice by several times. Even mixtures of old and new rice were found to show much difference in the concentration of citric acid and malic acid. CONCLUSION: A green analytical method has been developed for the simultaneous determination of CCAs by LC/MS analysis, and the identification of old rice samples from new ones was easily carried out according to their CCA content for the first time. The results indicated that the described method has powerful potential for the accurate identification of old rice samples from new ones.

Exposure to nickel chloride induces epigenetic modification on detoxification enzyme glutathione S-transferase M2.

Nickel (Ni) is a human carcinogen with genotoxic and epigenotoxic effects. Environmental and occupational exposure to Ni increases the risk of cancer and chronic inflammatory diseases. Our previous findings indicate that Ni alters gene expression through epigenetic regulation, specifically impacting E-cadherin and angiopoietin-like 4 (ANGPTL4), involved in epithelial-mesenchymal transition and migration. GST-M2, a member of the glutathione S-transferase (GST) enzyme family, plays a crucial role in cellular defense against oxidative damage and has been increasingly associated with cancer. GST-M2 overexpression inhibits lung cancer invasion and metastasis in vitro and in vivo. Hypermethylation of its promoter in cancer cells reduces gene expression, correlating with poor prognosis in non-small-cell lung cancer patients. The impact of Ni on GST-M2 remains unclear. We will investigate whether nickel exerts regulatory effects on GST-M2 through epigenetic modifications. Additionally, metformin, an antidiabetic drug, is being studied as a chemopreventive agent against nickel-induced damage. Our findings indicate that nickel chloride (NiCl2 ) exposure, both short-term and long-term, represses GST-M2 expression. However, the expression can be restored by demethylation agent 5-aza-2'-deoxycytidine and metformin. NiCl2 promotes hypermethylation of the GST-M2 promoter, as confirmed by methylation-specific PCR and bisulfite sequencing. Additionally, NiCl2 also influences histone acetylation, and metformin counteracts the suppressive effect of NiCl2 on histone H3 expression. Metformin reestablishes the binding of specificity protein 1 to the GST-M2 promoter, which is otherwise disrupted by NiCl2 . These findings elucidate the mechanism by which Ni reduces GST-M2 expression and transcriptional activity, potentially contributing to Ni-induced lung carcinogenesis.

Integrin αV Inhibition by GMI, a Ganoderma Microsporum Immunomodulatory Protein, Abolish Stemness and Migration in EGFR-Mutated Lung Cancer Cells Resistant to Osimertinib.

Integrins, the receptors of the extracellular matrix, are critical in the proliferation and metastasis of cancer cells. GMI, a Ganoderma microsporum immunomodulatory protein, possesses anticancer and antivirus abilities. The object of this study is to investigate the role of GMI in the integrins signaling pathway in lung cancer cells that harbor the EGFR L858R/T790M double mutation and osimertinib-resistance. Liquid chromatography-mass spectrometry and western blot assay were used to investigate the effect of GMI on inhibiting the protein expressions of integrins in H1975 cells. The migration ability and xenograft tumor growth of H1975 were suppressed by GMI. To elucidate the role of the integrin family in lung cancer resistant to osimertinib (AZD-9291, Tagrisso), H1975 cells were used to establish the osimertinib-resistant cells, named H1975/TR cells. The expressions of Integrin αV and stemness markers were much higher in H1975/TR cells than in H1975 cells. GMI suppressed cell viability, tumor spheroid growth, and the expressions of integrin αV and ß1 in H1975/TR cells. Furthermore, GMI suppressed the expressions of stemness markers and formation of tumor spheres via blocking integrin αV signaling cascade. This is the first study to reveal the novel function of GMI in constraining cancer stem cells and migration by abolishing the integrin αV-related signaling pathway in EGFR-mutated and osimertinib-resistant lung cancer cells.

3D intraoral scanning techniques support the effects of crown morphology on dental caries.

BACKGROUND: With the development and utilization of three-dimensional (3D) intraoral scanning (IOS) technology, the morphological characteristics of teeth were quantitatively assessed. In this research, we aimed to explore the prevalence of dental caries in relation to each measurable morphological indicator of the tooth body via 3D intraoral scanning techniques. METHODS: A hospital-based single-centre study was conducted at our hospital from Dec. 2021 to Apr. 2023. A total of 53 patients were involved in the study, providing complete morphological data for 79 teeth. Each patient completed an oral hygiene routine questionnaire and underwent examination by an experienced dentist to evaluate caries conditions before undergoing 3D intraoral scanning to obtain a digital dental model. Geomagic Studio 2014 was used to extract oral morphological data from the models. The acquired data were entered, cleaned and edited using Excel 2016 and subsequently exported to SPSS version 25.0 for analysis. Chi-square analysis and logistic regression analyses were employed to test the associations. RESULTS: Among the participants, 33 (61.1%) were female, with a mean age of 26.52 ± 10.83 years. Significant associations were found between dental caries and the vertical distance between the distal tip and the gum (OR 14.02; 95% CI 1.80-109.07; P = 0.012), the distal lateral horizontal distance of occlusion (OR 0.40; 95% CI 0.18-0.90; P = 0.026), and the mesial horizontal distance of occlusion (OR 2.20; 95% CI 1.12-4.31; P = 0.021). The Hosmer-Lemeshow test indicated a P value of 0.33. CONCLUSIONS: The vertical distance between the distal tip and the gum, the distal lateral horizontal distance of the occlusion and the mesial horizontal distance of the occlusion were the influencing factors for dental caries (identified as independent risk factors). We hypothesize that these factors may be associated with the physiological curvature of teeth and the role of chewing grooves in plaque formation over time. However, further studies involving larger population samples and more detailed age stratification are still needed.

Impact of age-friendly living environment and intrinsic capacity on functional ability in older adults: a cross-sectional study.

BACKGROUND: The World Health Organization (WHO) has proposed healthy aging framework, supposing that intrinsic capacity (IC), environment and their interaction may have influence on functional ability (FA). It was still unclear how the IC level and age-friendly living environment impact on FA. This study aims to confirm the relationship between the IC level and age-friendly living environment with FA, especially in older adults with low IC. METHODS: Four hundred eighty-five community-dwelling residents aged ≥ 60 years were enrolled. IC constructed by locomotion, cognition, psychological, vitality, and sensory domains was assessed using full assessment tools recommended by WHO. Age-friendly living environment was measured with 12 questions adapted from the spatial indicators framework of age-friendly cities. FA was assessed using activities of daily living (ADL) and one question about mobile payment ability. Multivariate logistic regression was used to explore the association between IC, environment and FA. The influence of the environment on electronic payment and ADL under the IC layer was assessed. RESULTS: Of 485 respondents, 89 (18.4%) had ADL impairment, and 166 (34.2%) had mobile payment function impairment. Limited IC (odds ratio [OR] = 0.783, 95% confidence interval [CI] = 0.621-0.988) and poor environment (OR = 0.839, 95% CI = 0.733-0.960) were associated with mobile payment ability impairment. Our results suggested that a supportive age-friendly living environment influenced FA was more prominent in older adults with poor IC (OR = 0.650, 95% CI = 0.491-0.861). CONCLUSIONS: Our results confirmed IC and the environment had an impact on mobile payment ability. The relationship between environment and FA showed differences according to IC level. These findings suggest that an age-friendly living environment is important to maintain and enhance elders' FA, especially in those with poor IC.

Geospatial epidemiology of Toxoplasma gondii infection in livestock, pets, and humans in China, 1984-2020.

Undercooked or raw meat containing cyst-stage bradyzoites and oocyst-contaminated pets are presumed to constitute a major source of human toxoplasmosis. As the geospatial epidemiology of Toxoplasma gondii (T. gondii) infection in livestock, pets, and humans is rarely studied in China, we undertook a geospatial analysis using GIS visualization techniques. The present study retrieved information from the PubMed, China National Knowledge Infrastructure, and Baidu Scholar databases from 1984 up to 2020. All the data about the seroprevalence of T. gondii in livestock (sheep and goats, pigs, cattle and yaks), pets (cats, dogs), and humans in China were collected. Geospatial epidemiology of T. gondii infection in these hosts was performed using GIS. Results revealed that the estimated pooled seroprevalence of T. gondii was ranged from 3.98 to 43.02% in sheep and goats in China, 0.75 to 30.34% in cattle and yaks, 10.45 to 66.47% in pigs, 2.50 to 60.00% in cats, 0.56 to 27.65% in dogs, and 0.72 to 23.41% in humans. The higher seroprevalences of T. gondii were observed in sheep and goats in the districts of Chongqing, Zhejiang, and Beijing. The infection rates of T. gondii in cattle and yaks were higher in Guizhou, Zhejiang, and Chongqing. Also, the pigs from Chongqing and Guizhou were most severely infected with T. gondii. For cats, the districts of Shanxi, Hebei, and Yunnan had higher seroprevalences of T. gondii and, the infections among dogs were higher in Yunnan and Hebei as well. Furthermore, higher infection pressure of T. gondii exists in the districts of Taiwan and Tibet in humans. The geographical and spatial distribution of toxoplasmosis indicated that infection with T. gondii was widely spread in China, with a wide range of variations among the different hosts and regions in the country. Our results suggested that livestock and pets are not only a reservoir for the parasite but also a direct source of T. gondii infection for humans. It is important to control T. gondii infections in these animals that would reduce the risk of toxoplasmosis in humans.

Current status and etiology of valvular heart disease in China: a population-based survey.

BACKGROUND: The epidemiology of valvular heart disease (VHD) has changed markedly over the last 50 years worldwide, and the prevalence and features of VHD in China are unknown. The objective of this study was to investigate the current status and etiology of VHD in China. METHODS: We used a cross-sectional national survey with stratified multistage random sampling from the general Chinese population to estimate the VHD burden. Data on demographic characteristics, medical history, physical examination, blood tests, and potential etiology were collected. Echocardiography was used to detect VHD. RESULTS: The national survey enrolled 34,994 people aged 35 years or older across China. Overall, 31,499 people were included in the final analysis, and 1309 participants were diagnosed with VHD. The weighted prevalence was 3.8%, with an estimated 25 million patients in China. The prevalence of VHD increased with age and was higher in participants with hypertension or chronic kidney disease than in their counterparts. Among participants with VHD, 55.1% were rheumatic and 21.3% were degenerative. The proportion of rheumatic decreased with age, and the proportion of degenerative rose with age. However, the prevalence of rheumatic disease was still higher in the elderly population than in the younger population. Logistic regression revealed that age and hypertension were correlated with VHD. CONCLUSIONS: In China, rheumatic heart disease was still the major cause of the VHD, with a significant increase in degenerative heart disease. Age and hypertension are important and easily identifiable markers of VHD.

Circulating MicroRNA-423-3p Improves the Prediction of Coronary Artery Disease in a General Population　- Six-Year Follow-up Results From the China-Cardiovascular Disease Study.

BACKGROUND: Circulating microRNAs (miRNA) are potential prognostic biomarkers for cardiovascular disease. We aimed to identify serum miRNA as an effective predictor for coronary artery disease (CAD) events in a general population cohort.Methods and Results:Serum miRNAs associated with CAD were determined by small RNA sequencing and quantitative RT-PCR. Further, the predictive ability of identified serum miRNAs was measured in a general population of 2,812 people. As a main outcome measure, CAD events were collected for 6 years and included acute myocardial infarction and subsequent myocardial infarction. Out of the 48 miRNA candidates, 5 miRNAs (miR-10a-5p, miR-126-3p, miR-210-3p, miR-423-3p and miR-92a-3p) showed better reliability and repeatability in serum. Then, the association of serum levels of the 5 miRNAs with CAD was validated. Furthermore, miR-10a-5p and miR-423-3p, which showed better performance, were tested in the large cohort, with a median follow up of 6.0 years. In multivariable Cox regression analysis, only miR-423-3p (P for trend<0.001) was able to precisely predict CAD events. Moreover, the addition of circulating miR-423-3p with the traditional risk factors together markedly improved the various model performance measures, including the area under the operating characteristics curve (0.782 vs. 0.806), Akaike Information Criterion (965.845 vs. 943.113) and net reclassification improvement (19.18%). CONCLUSIONS: Circulating miR-423-3p can improve the prediction of primary CAD outcomes on the basis of a traditional risk factor model in general population.

Metformin Mitigates Nickel-Elicited Angiopoietin-Like Protein 4 Expression via HIF-1α for Lung Tumorigenesis.

Nickel (Ni), which is a carcinogenic workplace hazard, increases the risk of lung cancer. Angiopoietin-like protein 4 (ANGPTL4) is a multifunctional cytokine that is involved in both angiogenesis and metastasis, but its role in lung cancer is still not clear. In this study, we assessed the role of ANGPTL4 in lung carcinogenesis under nickel exposure and investigated the effects of the antidiabetic drug metformin on ANGPTL4 expression and lung cancer chemoprevention. Our results showed that ANGPTL4 is increased in NiCl2-treated lung cells in a dose- and time-course manner. The expression of ANGPTL4 and HIF-1α induced by NiCl2 were significantly repressed after metformin treatment. The downregulation of HIF-1α expression by ROS savenger and HIF-1α inhibitor or knockdown by lentiviral shRNA infection diminished NiCl2-activated ANGPTL4 expression. Chromatin immunoprecipitation and the luciferase assay revealed that NiCl2-induced HIF-1α hypoxia response element interactions activate ANGPTL4 expression, which is then inhibited by metformin. In conclusion, the increased presence of ANGPTL4 due to HIF-1α accumulation that is caused by nickel in lung cells may be one mechanism by which nickel exposure contributes to lung cancer progression. Additionally, metformin has the ability to prevent NiCl2-induced ANGPTL4 through inhibiting HIF-1α expression and its binding activity. These results provide evidence that metformin in oncology therapeutics could be a beneficial chemopreventive agent.

Ni-induced TGF-ß signaling promotes VEGF-a secretion via integrin ß3 upregulation.

Nickel compounds are associated with lung and skin cancer incidence increase and accumulation of nickel in the body contributes to carcinogenesis. Upregulation of certain integrins in the primary tumor is associated with cancer metastasis and poor prognosis. However, the molecular mechanisms of nickel-induced cancer metastasis are still unclear. The purpose of the present study was to investigate the effects of nickel chloride (NiCl2 ) on the progression of cancer during metastasis. The results of showed that NiCl2 induces the expression of integrin ß3 mRNA and protein in a dose- and time-dependent manner. Inhibition of integrin αvß3 activation by ITGB3 ligand mimetics and GR144053, as well as downregulation of ITGB3 by lentiviral shRNA gene silencing, diminished NiCl2 -induced secretion of vascular endothelial growth factor-a (VEGF-a). Furthermore, pretreatment with type I TGF-ß receptor inhibitor, SB525334, suppressed the expression of ITGB3 at cell surface and secretion of VEGF-a in NiCl2 -treated cells. In conclusion, NiCl2 induces the expression of ITGB3 through TGF-ß signaling activation, followed by increasing VEGF-a secretion, revealing a novel role for ITGB3 in nickel compound-induced cancer metastasis and tumor angiogenesis.

A single nucleotide polymorphism in the BART promoter region of Epstein-Barr virus isolated from nasopharyngeal cancer cells.

Epstein-Barr virus (EBV) encodes BamHIA rightward transcript (BART) microRNAs (miRNAs). These miRNAs are expressed at high levels in epithelial tumors, such as nasopharyngeal carcinoma (NPC). BART miRNAs play important roles in EBV-associated malignancies, however, the reason for their high expression in NPC is unclear. We performed multiple sequence alignment of six completely sequenced EBV strains: Akata, YCCEL1, SNU719, C666-1, Mutu I, and M81. A single-nucleotide deletion was identified at the promoter region of BART. The luciferase assay suggested that this single-nucleotide polymorphism (SNP) significantly increased BART promoter activity. In addition to deletion, substitution at the same site also increased BART promoter activity. Analysis of the 170 EBV genome sequences from NPC and EBV-associated gastric cancers revealed that the frequency of this SNP was associated with NPC incidence and this SNP was found to be accumulated in the BART promoter region. Overall, our results suggested that this SNP should enhance BART promoter activity and thus, might contribute to the development of EBV-associated epithelial malignancies.

Epithelial growth factor receptor tyrosine kinase inhibitors alleviate house dust mite allergen Der p2-induced IL-6 and IL-8.

Steroid-insensitive asthma-related airway inflammation is associated with the expression of epidermal growth factor receptor (EGFR) tyrosine kinase in asthmatic bronchial epithelium. Proinflammatory cytokines IL-6 and IL-8 are related to steroid-insensitive asthma. It is currently unknown how EGFR-tyrosine kinase inhibitors (EGFR-TKIs) affects house dust mite (HDM)-induced asthma in terms of inflammatory cytokines related to steroid-resistant asthma and further signaling pathway. Cytokine expressions and EGFR signaling pathway were performed by ELISA, reverse transcriptase PCR, real-time PCR, and Western blot in cell-line models. AMP-activated protein kinase (AMPK) pathway-related inhibitors were applied to confirm the association between EGFR-TKI and AMPK pathway. HDM induced IL-6 and IL-8 in a dose-dependent manner. Both Erlotinib (Tarceva) and Osimertinib (AZD-9291) reduced the levels of HDM-stimulated IL-6 and IL-8 levels in BEAS-2B cells. AZD-9291 was more effective than Erlotinib in inhibiting phospho-EGFR, and downstream phosphatidylinositol-3-kinase/protein kinase B (PI3K/AKT) and phopho-signal transducer and activator of transcription 3 (p-STAT3) pathway signaling. In addition, AMPK pathway-related inhibitor, Calcium-/calmodulin-dependent protein kinase kinase ß (CaMKKß) inhibitor, down-regulated IL-8, but EGFR-TKI had no effect on AMPK pathway. Our findings highlight EGFR-TKIs, Tarceva, and AZD-9291, attenuate HDM-induced inflammatory IL-6 and IL-8 cytokines via EGFR signaling axis pathway, but not AMPK signaling pathway.

Relationship of genetic variant distributions of WW domain-containing oxidoreductase gene with uterine cervical cancer.

To our knowledge, no study investigates the association of genetic variant distributions of WW domain-containing oxidoreductase (WWOX) gene with development of invasive cancer, clinicopathologic variables and patient survival in uterine cervical cancer for Taiwanese women. We therefore conducted this study to explore the clinical involvements of WWOX single nucleotide polymorphisms (SNPs) in cervical cancer. One hundred and thirty-one patients with cervical invasive cancer and 93 patients with precancerous lesions as well as 316 control women were consecutively enrolled. The genotypic frequencies of WWOX genetic variants rs73569323, rs383362, rs11545028, rs3764340 and rs12918952 were determined by real-time polymerase chain reaction. The results revealed that only WWOX SNP rs3764340 was associated between patients with cervical invasive cancer and normal controls among 5 WWOX genetic variants. Cervical cancer patients with genotypes GA/AA in WWOX SNP rs12918952 were associated with parametrium invasion and pelvic lymph node metastasis. Univariate analysis found that WWOX SNPs rs73569323 and rs11545028 were associated with patient survival, whereas multivariate analysis revealed CT/TT in rs11545028 was the only genetic variant, which could predict better overall survival, among 5 WWOX SNPs in Taiwan. In conclusion, Taiwanese women with CG/GG in WWOX SNP rs3764340 are susceptible to cervical invasive cancer. Cervical cancer patients with GA/AA in rs12918952 tend to have more risk to develop parametrium invasion and pelvic lymph node metastasis. Among 5 WWOX SNPs, rs11545028 is the only genetic variant associated with patient survival, in which CT/TT could predict better overall survival in Taiwanese women.

Direct-Writing of Cu Nano-Patterns with an Electron Beam.

We demonstrate direct electron beam writing of a nano-scale Cu pattern on a surface with a thin aqueous layer of CuSO4 solution. Electron beams are highly maneuverable down to nano-scales. Aqueous solutions facilitate a plentiful metal ion supply for practical industrial applications, which may require continued reliable writing of sophisticated patterns. A thin aqueous layer on a surface helps to confine the writing on the surface. For this demonstration, liquid sample holder (K-kit) for transmission electron microscope (TEM) was employed to form a sealed space in a TEM. The aqueous CuSO4 solution inside the sample holder was allowed to partially dry until a uniform thin layer was left on the surface. The electron beam thus reduced Cu ions in the solution to form the desired patterns. Furthermore, the influence of e-beam exposure time and CuSO4(aq) concentration on the Cu reduction was studied in this work. Two growth stages of Cu were shown in the plot of Cu thickness versus e-beam exposure time. The measured Cu reduction rate was found to be proportional to the CuSO4(aq) concentration.

Household polluting cooking fuels and intrinsic capacity among older population: A harmonized nationwide analysis in India and China.

BACKGROUNDS: Household polluting cooking fuels, as an important changeable behavior, are related to various detrimental health effects among the elderly. There is limited research on the association between polluting cooking fuel use and intrinsic capacity (IC) as an indicator of healthy aging. This study aimed to evaluate the above-mentioned association in India and China, where polluting cooking fuel use is common. METHODS: We enrolled 33,803 participants aged ≥60 years from two nationally representative studies: the Longitudinal Aging Study in India and the China Health and Retirement Longitudinal Study. Polluting cooking fuel use was defined as a self-report of using wood, coal, kerosene, crop residue, or dung. IC was measured by five aspects, including locomotion, cognition, vitality, sensory, and psychological capacity. The random-effects mixed linear regression and logistic regression with population weighting were performed. Multivariable-adjusted model and propensity score were used to adjust for potential confounders. RESULTS: A total of 47.54 % and 59.32 % of elderly adults reported primary cooking using polluting fuels in India and China, respectively. Using polluting cooking fuels was consistently associated with IC decline; particularly, cognitive capacity was the most susceptible domain. In India, participants using polluting fuels had a 1.062 (95 % confidence interval [CI]: 1.047-1.078) times risk for IC deficits, whereas more prominent results were observed in China (odds ratio [OR]: 2.040, 95 % CI: 1.642-2.533). Such harmful effects might be alleviated by transferring from polluting to clean fuels. Additionally, the duration of polluting fuel use was also positively associated with IC deficits. CONCLUSION: This study provided substantial public implications on healthy aging for the elderly population at a global scale, strengthening the importance of health education and policy efforts to accelerate the transition from polluting to clean fuels.

Mediating effects of physical activities and cognitive function on the relationship between dietary diversity and all-cause mortality in community-dwelling older adults.

Background: Although dietary diversity (DD) has been confirmed to be associated with multiple health outcomes and longevity in older people, the related mechanisms have not been elucidated. In this study, we explored the mediating roles of physical activities and cognitive function in the relationship between DD and all-cause mortality. Methods: We recruited 34 068 community-dwelling older adults aged ≥60 years from the Chinese Longitudinal Healthy Longevity Study and followed them up until 2018. Dietary diversity score (DDS) was assessed by the intake frequency of nine food sources. We evaluated physical activities and cognitive function using the Katz index and Mini-Mental State Examination. We explored the mediating roles of physical activities and cognitive function between DDS and all-cause mortality using mediated analyses in Cox proportional risk regression models. Results: A total of 25 362 deaths were recorded during 148 188.03 person-years of follow-up. Participants with physical disability and cognitive impairment had lower DDS than the normal group (P < 0.001). After controlling for all covariates, DDS, physical activities, and cognitive functioning were negatively associated with all-cause mortality. Physical activities and cognitive function mediated 18.29% (95% confidence interval (CI) = 12.90-23.10) and 27.84% (95% CI = 17.52-37.56) of the total effect of DDS on mortality, respectively. Conclusions: Physical activities and cognitive function mediated the association between DDS and all-cause mortality. Maintaining DD may benefit early death prevention by reducing physical disability and cognitive impairment in community-dwelling older people.

Epidemiology and Azole Resistance of Clinical Isolates of Aspergillus fumigatus from a Large Tertiary Hospital in Ningxia, China.

Purpose: The objective of this study was to determine the clinical distribution, in vitro antifungal susceptibility and underlying resistance mechanisms of Aspergillus fumigatus (A. fumigatus) isolates from the General Hospital of Ningxia Medical University between November 2021 and May 2023. Methods: Antifungal susceptibility testing was performed using the Sensititre YeastOne YO10, and isolates with high minimal inhibitory concentrations (MICs) were further confirmed using the standard broth microdilution assays established by the Clinical and Laboratory Standards Institute (CLSI) M38-third edition. Whole-Genome Resequencing and RT-qPCR in azole-resistant A. fumigatus strains were performed to investigate the underlying resistance mechanisms. Results: Overall, a total of 276 A. fumigatus isolates were identified from various clinical departments, showing an increasing trend in the number of isolates over the past 3 years. Two azole-resistant A. fumigatus strains (0.72%) were observed, one of which showed overexpression of cyp51A, cyp51B, cdr1B, MDR1/2, artR, srbA, erg24A, and erg4B, but no cyp51A mutation. However, the other strain harbored two alterations in the cyp51A sequences (L98H/S297T). Therefore, we first described two azole-resistant clinical A. fumigatus strains in Ningxia, China, and reported one azole-resistant strain that has the L98H/S297T mutations in the cyp51A gene without any tandem repeat (TR) sequences in the promoter region. Conclusions: This study emphasizes the importance of enhancing attention and surveillance of azole-resistant A. fumigatus, particularly those with non-TR point mutations of cyp51A or non-cyp51A mutations, in order to gain a better understanding of their prevalence and spread in the region.

The Expression of TP63 as a Biomarker of Early Recurrence in Resected Esophageal Squamous Cell Carcinoma after Neoadjuvant Chemoradiotherapy.

Esophageal cancer ranks among the ten most common cancers worldwide. Despite the adoption of neoadjuvant concurrent chemoradiotherapy (nCCRT) followed by surgery as the standard treatment approach in recent years, the local recurrence rate remains high. In this study, we employed RNA-seq to investigate distinctive gene expression profiles in esophageal squamous cell carcinoma (ESCC) with or without recurrence following a standard treatment course. Our findings indicate that recurrent ESCC exhibits heightened keratinizing and epidermis development activity compared to non-recurrent ESCC. We identified TP63 as a potential candidate for distinguishing clinical outcomes. Furthermore, immunohistochemistry confirmed the trend of TP63 overexpression in ESCC recurrence. Patients with elevated TP63 expression had poorer overall survival and lower 3-year recurrence-free survival. This study underscores the potential of TP63 as a biomarker for detecting cancer recurrence and suggests its role in guiding future treatment options.

Mendelian randomization supports causal effects of inflammatory biomarkers on myopic refractive errors.

AIMS: To determine whether inflammatory biomarkers are causal risk factors for more myopic refractive errors. METHODS: Northern Sweden Population Health Study (NSPHS), providing inflammatory biomarkers data; UK Biobank, providing refractive errors data. 95,619 European men and women aged 40 to 69 years with available information of refractive errors and inflammatory biomakers. Inflammatory biomarkers including ADA, CCL23, CCL25, CD6, CD40, CDCP-1, CST5, CXCL-5, CXCL-6, CXCL-10, IL-10RB, IL-12B, IL-15RA, IL-18R1, MCP-2, MMP-1, TGF-ß1, TNF-ß, TWEAK and VEGF-A were exposures, and spherical equivalent (SE) using the formula SE = sphere + (cylinder/2) was outcome. RESULTS: Mendelian randomization analyses showed that each unit increase in VEGF-A, CD6, MCP-2 were causally related to a more myopic refractive errors of 0.040 D/pg.mL-1 (95% confidence interval 0.019 to 0.062; P = 2.031 × 10-4), 0.042 D/pg.mL-1 (0.027 to 0.057; P = 7.361 × 10-8) and 0.016 D/pg.mL-1 (0.004 to 0.028; P = 0.009), and each unit increase in TWEAK was causally related to a less myopic refractive errors of 0.104 D/pg.mL-1 (-0.152 to -0.055; P = 2.878 × 10-5). Tested by the MR-Egger, weighted median, MR-PRESSO, Leave-one-out methods, our results were robust to horizontal pleiotropy and heterogeneity in VEGF-A, MCP-2, CD6, but not in TWEAK. CONCLUSIONS: Our Mendelian Randomization analysis supported the causal effects of VEGF-A, MCP-2, CD6 and TWEAK on myopic refractive errors. These findings are important for providing new indicators for early intervention of myopia to make myopic eyesight threatening consequences less inevitable.