Relations between near-field enhancements and Purcell factors in hybrid nanostructures of plasmonic antennas and dielectric cavities.

Strong near-field enhancements (NFEs) of nanophotonic structures are believed to be closely related to high Purcell factors (FP). Here, we theoretically show that the correlation is partially correct; the extinction cross section (σ) response is also critical in determining FP. The divergence between NFE and FP is especially pronounced in plasmonic-dielectric hybrid systems, where the plasmonic antenna supports dipolar plasmon modes and the dielectric cavity hosts Mie-like resonances. The cavity's enhanced-field environment can boost the antenna's NFEs, but the FP is not increased concurrently due to the larger effective σ that is intrinsic to the FP calculations. Interestingly, the peak FP for the coupled system can be predicted by using the NFE and σ responses. Furthermore, the limits for FP of coupled systems are considered; they are determined by the sum of the FP of a redshifted (or modified, if applicable) antenna and an individual cavity. This contrasts starkly with the behavior of NFE which is closely associated with the multiplicative effects of the NFEs provided by the antenna and the dielectric cavity. The differing behaviors of NFE and FP in hybrid cavities have varied impacts on relevant nanophotonic applications such as fluorescence, Raman scattering and enhanced light-matter interactions.

Comprehensive treatment of deep frostbite of multiple fingers after trauma: A case report.

BACKGROUND: Frostbite is becoming increasingly common in urban environments, and severe cases can lead to tissue loss. The treatment goal is to preserve tissue and function; the sooner appropriate treatment is administered, the more tissue can be saved. However, not every patient with deep frostbite seeks medical care promptly. CASE SUMMARY: We report the case of a 73-year-old male patient who was lost in the wilderness for 2 d due to trauma and confusion. He experienced deep frostbite on multiple fingers. Treatment should not be discontinued for patients with deep frostbite who present after the optimum treatment timing. Bullae that no longer form (bloody) blisters within 24 h of aspiration should be removed. Mucopolysaccharide polysulfate cream has clinical value in frostbite treatment. The patient was transferred to Chinese Academy of Medical Sciences and Peking Union Medical College Hospital 12 h after being rescued. The patient had contraindications for thrombolysis, the most effective treatment, due to intracranial hemorrhage and presenting past the optimum treatment timing. We devised a comprehensive treatment plan, which involved delayed use vasodilators and high-pressure oxygen therapy at day 49 post-injury. We experimented with mucopolysaccharide polysulfate cream to treat the frostbite. The aim of the treatment was to safeguard as much tissue as possible. In the end, the fingers that suffered from frostbite were able to be partially preserved. CONCLUSION: The case indicated that patients with severe frostbite who missed the optimal treatment time and had contraindications for thrombolysis could still partially preserve the affected limbs through comprehensive treatment.

FGF10 mitigates doxorubicin-induced myocardial toxicity in mice via activation of FGFR2b/PHLDA1/AKT axis.

Doxorubicin is a common chemotherapeutic agent in clinic, but myocardial toxicity limits its use. Fibroblast growth factor (FGF) 10, a multifunctional paracrine growth factor, plays diverse roles in embryonic and postnatal heart development as well as in cardiac regeneration and repair. In this study we investigated the role of FGF10 as a potential modulator of doxorubicin-induced cardiac cytotoxicity and the underlying molecular mechanisms. Fgf10+/- mice and an inducible dominant negative FGFR2b transgenic mouse model (Rosa26rtTA; tet(O)sFgfr2b) were used to determine the effect of Fgf10 hypomorph or blocking of endogenous FGFR2b ligands activity on doxorubicin-induced myocardial injury. Acute myocardial injury was induced by a single injection of doxorubicin (25 mg/kg, i.p.). Then cardiac function was evaluated using echocardiography, and DNA damage, oxidative stress and apoptosis in cardiac tissue were assessed. We showed that doxorubicin treatment markedly decreased the expression of FGFR2b ligands including FGF10 in cardiac tissue of wild type mice, whereas Fgf10+/- mice exhibited a greater degree of oxidative stress, DNA damage and apoptosis as compared with the Fgf10+/+ control. Pre-treatment with recombinant FGF10 protein significantly attenuated doxorubicin-induced oxidative stress, DNA damage and apoptosis both in doxorubicin-treated mice and in doxorubicin-treated HL-1 cells and NRCMs. We demonstrated that FGF10 protected against doxorubicin-induced myocardial toxicity via activation of FGFR2/Pleckstrin homology-like domain family A member 1 (PHLDA1)/Akt axis. Overall, our results unveil a potent protective effect of FGF10 against doxorubicin-induced myocardial injury and identify FGFR2b/PHLDA1/Akt axis as a potential therapeutic target for patients receiving doxorubicin treatment.

Evaluation and Use of Organs from Donors Poisoned by Organophosphorus Pesticide.

BACKGROUND The aim of this study was to explore the evaluation and use of donor organs from donors with brain death caused by acute severe organophosphorus pesticides and provide a basis for the use of such donor organs. MATERIAL AND METHODS Seven cases of brain dead donors caused by acute organophosphorus pesticide poisoning from January 2014 to December 2018 in the hospital were collected, and a retrospective analysis was made of the donors' age, race, physiological and pathological changes, donor organ function changes and the organ use, liver or kidney function recovery, and complications of the recipients. The 18 recipients were followed up until June 31, 2022. RESULTS We found that 71.42% of organ donors were male, and 71.42% of organ donors were under 50 years old. The main cause of death was respiratory failure caused by organophosphorus pesticide poisoning. The liver and kidney functions of 7 donors were damaged, and 3 livers could not be used due to severe functional damage, but the liver or kidney function of 18 recipients gradually recovered after transplantation. Delayed recovery of graft function occurred after transplantation accounted for 21.43%, and the grafts had good short-term to medium-term performance. CONCLUSIONS Although the function of organs from donor with brain death due to acute severe organophosphorus pesticide poisoning is seriously damaged, most of the organs can still be used for transplantation. Individualized functional maintenance according to the situation of donors is conducive to improving the quality of organs.

Cuproplasia characterization in colon cancer assists to predict prognosis and immunotherapeutic response.

Introduction: Colon cancer is the 3rd most prevalent cancer worldwide, with more than 900,000 deaths annually. Chemotherapy, targeted treatment, and immunotherapeutic treatment are the three cornerstones of colon cancer treatment; however, the occurrence of immune therapy resistance is the most pressing problem to solve. Copper is a mineral nutrient that is both beneficial and potentially toxic to cells and is increasingly implicated in cell proliferation and death pathways. Cuproplasia is characterized by copper-dependent cell growth and proliferation. This term encompasses both neoplasia and hyperplasia and describes the primary and secondary effects of copper. The connection between copper and cancer has been noted for decades. However, the relationship between cuproplasia and colon cancer prognosis remains unclear. Method: In this study, we applied bioinformatics approaches including WGCNA, GSEA and etc. to delineate cuproplasia characterization of colon cancer, set up a robust Cu_riskScore model based on cuproplasia-relevant genes and found its relevant biological processes use qRT-pCR to validate our results on our cohort. Result: The Cu_riskScore is found to be relevant to Stage and MSI-H subtype, and some biological processes including MYOGENESIS and MYC TARGETS. The Cu_riskScore high and low groups also showed different immune infiltration pattern and genomic traits. Finally, the result of our cohort showed the Cu_riskScore gene RNF113A has a marked effect in predicting immunotherapy response. Discussion: In conclusion, we identified a cuproplasia-related gene expression signature consisting of six genes and studied the landscape of the clinical and biological characterization of this model in Colon Cancer. Furthermore, the Cu_riskScore was demonstrated to be a robust prognostic indicator and predictive factor for the benefits of immunotherapy.

Research progress of sphingosine kinase and sphingosine-1-phosphate (S1P) /S1P receptor signaling in tumor microenvironment / 药学学报

Sphingosine kinase (SphK), sphingosine-1-phosphate (S1P) and S1P receptor (S1PR) are involved in the tumor biological processes such as tumor cell proliferation and migration, and play an important role in the development of cancer. In recent years, researchers have increasingly focused on the interaction between cancer cells and the tumor microenvironment. The tumor microenvironment is genetically stable and can be induced to an antitumor phenotype, which has significant therapeutic advantages. Studies have shown that SphK/S1P/S1PR can regulate multiple aspects of the tumor microenvironment. This review summarizes the effects of SphK and S1P/S1PR signaling on the tumor microenvironment from four perspectives: tumor immune microenvironment, cancer associated fibroblasts, tumor angiogenesis and tumor hypoxic microenvironment, and also outlines potential drug research related to these signal molecules, aiming to elucidate the role of SphK/S1P/S1PR in tumor occurrence and development and provide new ideas for the research of anti-tumor drugs.

ADCK1 is a potential therapeutic target of osteosarcoma.

We here showed that ADCK1 (AarF domain-containing kinase 1), a mitochondrial protein, is upregulated in human osteosarcoma (OS) tissues and OS cells. In primary and established OS cells, ADCK1 shRNA or CRISPR/Cas9-induced ADCK1 knockout (KO) remarkably inhibited cell viability, proliferation and migration, and provoked apoptosis activation. Conversely, ectopic ADCK1 overexpression exerted pro-cancerous activity by promoting OS cell proliferation and migration. ADCK1 depletion disrupted mitochondrial functions in OS cells and induced mitochondrial membrane potential reduction, ATP depletion, reactive oxygen species production. Significantly, ADCK1 silencing augmented doxorubicin-induced apoptosis in primary OS cells. mTOR activation is important for ADCK1 expression in OS cells. The mTOR inhibitors, rapamycin and AZD2014, as well as mTOR shRNA, potently decreased ADCK1 expression in primary OS cells. In nude mice, the growth of subcutaneous pOS-1 xenografts was largely inhibited when bearing ADCK1 shRNA or ADCK1 KO construct. Moreover, ADCK1 KO largely inhibited pOS-1 xenograft in situ growth in proximal tibia of nude mice. ADCK1 depletion, apoptosis activation and ATP reduction were detected in pOS-1 xenografts bearing ADCK1 shRNA or ADCK1 KO construct. Together, the mitochondrial protein ADCK1 is required for OS cell growth and is a novel therapeutic target of OS.

Long-term IgE immunological tolerance to peanut allergens: An alternative to Noon's daily desensitization paradigm.

Herein, we show that profound afferent long-term peanut-allergen-specific IgE immunological tolerance for 3 to 9 months induced sustained unresponsiveness (SU) in naïve or peanut-sensitized rodents after peanut allergen immunization. Rodents were vaccinated sublingually with a peanut allergen extract or recombinant peanut allergen in chenodeoxycholate (CDCA), a fanesoid X receptor (FXR, NR1H4) agonist that downregulates SREBP-1c (sterol regulatory element binding protein-1c) and upregulates SHP in bone marrow-derived tolerogenic dendritic cells (DCs). Approximately 90 âˆ¼ 95 % of the total circulating PE-potentiated IgE and Ara h1, Ara h 2, and Ara h 6 peanut allergen-specific IgE responses were suppressed by recombinant peanut allergen-conjugated solid magnetic beads (sensitivity of 0.2 IU/ml). In contrast, peanut allergen-specific IgG production was not affected. Similarly, oleoylethanolamine (OEA), a peroxisome proliferator-activator receptor alpha (PPARα) agonist, and GW9662, a PPARγ antagonist, induced long-term peanut-specific IgE tolerance when administered via the sublingual, oral or i.p. route. Prophylactic Ara h2 DNA immunization with caNRF2 and IL-35 coexpression induced Ara h2 IgE tolerance. In summary, peanut allergen vaccination with select natural molecular ligands of nuclear receptors induced long-term peanut allergen-specific IgE tolerance via the afferent limb, which indicates that vaccination is an immune tolerance-promoting strategy that is effective at the DC level and that differs from Noon's daily desensitization program, which is effective at the mast cell level.

Combination of Preoperative Circulating Tumor Cell Count and Neutrophil-Lymphocyte Ratio for Prognostic Prediction in Hepatocellular Carcinoma Patients after Curative Hepatectomy.

Background: Both the preoperative neutrophil-lymphocyte ratio (NLR) and circulating tumor cell count (CTC) are associated with poor prognosis in hepatocellular carcinoma (HCC). The purpose of this study was to explore the prognostic value of these two indices (CTC-NLR) in HCC. Methods: We retrospectively collected demographic and clinical data, including NLR and CTC, from 97 patients with HCC who underwent curative hepatectomy at our institution from March 2014 to May 2017. X-Tile software was used to confirm the optimal cut-off value of NLR and CTC for predicting overall survival (OS) in this study. OS were also analyzed using Kaplan-Meier and Cox regression methods. Based on preoperative CTC and NLR, patients were divided into three groups: CTC-NLR (0), CTC-NLR (1), and CTC-NLR (2). Relationships of CTC-NLR with clinicopathological factors and survival were evaluated. Results: Preoperatively, CTC positively correlated with NLR. Patients with NLR and CTC higher than the cut-offs had shorter OS than patients with low NLR and CTC. Kaplan-Meier analysis, and log-rank tests revealed significantly lower OS among patients with CTC-NLR scores of 0, 1, and 2. Uni- and multivariate analyses showed that CTC-NLR (hazard ratio 2.050, P = 0.005), CTC (hazard ratio 2.285, P = 0.032), and NLR (hazard ratio 1.902, P = 0.048) were independent predictor of OS. A time-dependent ROC curve indicated that the prognostic efficacy of the CTC-NLR at 1 year (0.714) was better than that of NLR (0.687) and CTC (0.590); the prognostic efficacy of the CTC-NLR at 2 years (0.746) was better than that of NLR (0.711) and CTC (0.601); the prognostic efficacy of the CTC-NLR at 3 years (0.742) was better than that of NLR (0.694) and CTC (0.629). Conclusions: HCC patients with higher NLR and CTC tend to show shorter OS. Preoperative CTC-NLR may be associated with poor survival and might be a reliable prognostic predictor in HCC after curative hepatectomy.

Identification and Validation in a Novel Quantification System of Ferroptosis Patterns for the Prediction of Prognosis and Immunotherapy Response in Left- and Right-Sided Colon Cancer.

Background: This study aimed to establish a novel quantification system of ferroptosis patterns and comprehensively analyze the relationship between ferroptosis score (FS) and the immune cell infiltration (ICI) characterization, tumor mutation burden (TMB), prognosis, and therapeutic sensitivity in left-sided and right-sided colon cancers (LCCs and RCCs, respectively). Methods: We comprehensively evaluated the ferroptosis patterns in 444 LCCs and RCCs based on 59 ferroptosis-related genes (FRGs). The FS was constructed to quantify ferroptosis patterns by using principal component analysis algorithms. Next, the prognostic value and therapeutic sensitivities were evaluated using multiple methods. Finally, we performed weighted gene co-expression network analysis (WGCNA) to identify the key FRGs. The IMvigor210 cohort, TCGA-COAD proteomics cohort, and Immunophenoscores were used to verify the predictive abilities of FS and the key FRGs. Results: Two ferroptosis clusters were determined. Ferroptosis cluster B demonstrated a high degree of congenital ICI and stromal-related signal enrichment with a poor prognosis. The prognosis, response of targeted inhibitors, and immunotherapy were significantly different between high and low FS groups (HSG and LSG, respectively). HSG was characterized by high TMB and microsatellite instability-high subtype with poor prognosis. Meanwhile, LSG was more likely to benefit from immunotherapy. ALOX5 was identified as a key FRG based on FS. Patients with high protein levels of ALOX5 had poorer prognoses. Conclusion: This work revealed that the evaluation of ferroptosis subtypes will contribute to gaining insight into the heterogeneity in LCCs and RCCs. The quantification for ferroptosis patterns played a non-negligible role in predicting ICI characterization, prognosis, and individualized immunotherapy strategies.

Clinical features and treatment outcomes of pediatric Langerhans cell histiocytosis with macrophage activation syndrome-hemophagocytic lymphohistiocytosis.

BACKGROUND: Langerhans cell histiocytosis (LCH) is a rare myeloid neoplasm. A few LCH patients had Macrophage activation syndrome-hemophagocytic lymphohistiocytosis (MAS-HLH), a life-threatening, hyper-inflammatory syndrome. We retrospectively described the clinical-biological characteristics of a series of 28 pediatric LCH patients with MAS-HLH in a single center. We further analyzed the difference in treatment outcomes between second-line chemotherapy (cytarabine and cladribine) and targeted therapy (dabrafenib) for BRAF-V600E-positive patients. RESULTS: LCH patients with MAS-HLH were aged < 2 years, harbored high frequencies of risk organ, skin, or lymph nodes involvement, and most of them carried BRAF-V600E mutation in lesions (88.0%) or plasma (90.5%). Patients were firstly treated with the initial induction first-line therapy (vindesine-steroid combination), and most of them (26/28) failed to control the active MAS-HLH after one six-week course of induction treatment. Then they were shifted to second-line chemotherapy or targeted therapy dabrafenib. BRAF-V600E-mutant patients treated with dabrafenib had prompt resolution of MAS-HLH signs and symptoms with less toxicity than second-line chemotherapy. Moreover, the progression-free survival (PFS) rate for patients given dabrafenib was much higher than those treated with chemotherapy (4 year-PFS: 75% vs. 14.6%, P = 0.034). CONCLUSIONS: LCH patients with MAS-HLH harbored specific clinical-biology characteristics compared to the multisystem LCH without MAS-HLH. The BRAF inhibitor dabrafenib provides a promising treatment option for LCH with MAS-HLH.

Implication of the hepatokine, fibrinogen-like protein 1 in liver diseases, metabolic disorders and cancer: The need to harness its full potential.

Fibrinogen-like protein 1 (FGL1) is a novel hepatokine that forms part of the fibrinogen superfamily. It is predominantly expressed in the liver under normal physiological conditions. When the liver is injured by external factors, such as chemical drugs and radiation, FGL1 acts as a protective factor to promote the growth of regenerated cells. However, elevated hepatic FGL1 under high fat conditions can cause lipid accumulation and inflammation, which in turn trigger the development of non-alcoholic fatty liver disease, diabetes, and obesity. FGL1 is also involved in the regulation of insulin resistance in adipose tissues and skeletal muscles as a means of communication between the liver and other tissues. In addition, the abnormally changed FGL1 levels in the plasma of cancer patients make it a potential predictor of cancer incidence in clinical practice. FGL1 was recently identified as a major functional ligand of the immune inhibitory receptor, lymphocyte-activation gene 3 (LAG3), thus making it a promising target for cancer immunotherapy except for the classical programmed cell death protein 1/programmed cell death ligand 1 (PD-1/PD-L1) axis. Despite the potential of FGL1 as a new cancer biomarker and therapeutic target, there are few related studies and much of what has been reported are superficial and lack depth and particularity. Therefore, elucidating the role and underlying mechanisms of FGL1 could be crucial for the development of promising diagnostic and therapeutic strategies for related diseases. Here, we provide a comprehensive review of the cellular mechanisms and clinical prospects of FGL1 in the prevention and treatment of liver diseases, metabolic disorders and cancer, and proffer suggestions for future studies.

Recent advances in isolation, identification, and culture of mammalian spermatogonial stem cells.

Continuous spermatogenesis depends on the self-renewal and differentiation of spermatogonial stem cells (SSCs). SSCs, the only male reproductive stem cells that transmit genetic material to subsequent generations, possess an inherent self-renewal ability, which allows the maintenance of a steady stem cell pool. SSCs eventually differentiate to produce sperm. However, in an in vitro culture system, SSCs can be induced to differentiate into various types of germ cells. Rodent SSCs are well defined, and a culture system has been successfully established for them. In contrast, available information on the biomolecular markers and a culture system for livestock SSCs is limited. This review summarizes the existing knowledge and research progress regarding mammalian SSCs to determine the mammalian spermatogenic process, the biology and niche of SSCs, the isolation and culture systems of SSCs, and the biomolecular markers and identification of SSCs. This information can be used for the effective utilization of SSCs in reproductive technologies for large livestock animals, enhancement of human male fertility, reproductive medicine, and protection of endangered species.

Significance of serum Th1/Th2 cytokine levels in underlying disease classification of childhood HLH.

OBJECT: Goal of this research was to investigate values of serum cytokines in childhood HLH with different triggers, with the expectation to find secretion spectrum of 5 main types of underlying diseases. METHOD: 118 newly diagnosed HLH were included, and serum concentrations of 6 cytokines were tested before treatment began. Absolute cytokine levels and ratios between them were then studied in the HLH groups collectively and separately RESULTS: In general, IFN-γ, IL-10 and IL-6 showed differences among 5 HLH groups. Specifically, relative levels of these three cytokines to each other were meaningful in distinguishing 4 types of HLH. Level of IL-6 was higher than those of IFN-γ or IL-10 in HLH driven by Systemic auto-inflammatory disorders (SAIDs) or Langerhans Cell Histiocytosis (LCH), while primary HLH and EBV-HLH shared elevated ratio of IL-10 to IL-6. Although more than one distinctive ratios were found in 3 HLH groups, combination of these parameters didn't offer optimal balance between sensitivity and specificity. CONCLUSION: As a group of easily gained laboratory findings, cytokine levels were reliable in the procedure of roughly classifying HLH cases with the help of patients' clinical phenotype. However, adequate data is still needed to explore the significance of these indicators in identifying one particular underlying disease accurately.

Prevalence and risk factors of deep venous thrombosis of lower extremity in patients with stage Ⅲ and Ⅳ pressure ulcers on admission / 中华烧伤杂志

Objective: To investigate the incidence and risk factors of deep venous thrombosis (DVT) of lower extremity in patients with stage Ⅲ and Ⅳ pressure ulcer on admission. Methods: A retrospective case series study was conducted. A total of 241 patients with stage Ⅲ and Ⅳ pressure ulcers who met the inclusion criteria and were discharged from the Department of Wound Repair of the First People's Hospital of Zhengzhou from January 1, 2015 to December 31, 2019 were enrolled in this study, including 134 males and 107 females, aged 22 to 93 years, with a median age of 68 years; 37 patients were with stage Ⅲ pressure ulcers and 204 patients were with stage Ⅳ pressure ulcers. The DVT occurrence of patients was recorded. According to whether DVT of lower extremity veins was diagnosed by color Doppler ultrasound within 48 h after admission or not, the patients were divided into DVT group (n=37) and non-DVT group (n=204). Data of patients in the two groups were collected and compared, including gender, age, duration of pressure ulcer, time in bed, and combination with diabetes, hypertension, coronary heart disease, cerebral infarction, pneumonia, sepsis/septic shock, and paraplegia, and the plasma D-dimer level and Caprini score within 24 h after admission. Data were statistically analyzed with independent sample t test, Mann-Whitney U test, chi-square test, and Fisher's exact probability test. The indicators with statistically significant differences between the two groups were analyzed with multivariate logistic regression analysis to screen the independent risk factors influencing the DVT of lower extremity in 241 patients with stage Ⅲ and Ⅳ pressure ulcers on admission. Results: The incidence of DVT of lower extremity was 15.4% (37/241), of which 86.5% (32/37) were asymptomatic DVT. Among the DVT of 46 lower limbs, only 29 involved the inferior genicular veins, accounting for 63.0%. There were no statistically significant differences in gender, duration of pressure ulcer, combination with diabetes, hypertension, coronary heart disease, cerebral infarction, pneumonia, and sepsis/septic shock of patients between the two groups (P>0.05), while there were statistically significant differences in age, time in bed, combination with paraplegia, the plasma D-dimer level and Caprini score of patients between the two groups(t=-3.19, Z=-2.04, χ2=4.44, Z=-3.89, t=-2.14, respectively, P<0.05 or P<0.01). Multivariate logistic regression analysis showed that age and plasma D-dimer level were independent risk factors influencing the DVT of lower extremity in 241 patients with stage Ⅲ and Ⅳ pressure ulcers on admission (with odds ratios of 1.03 and 1.18, respectively, with 95% confidence intervals of 1.00-1.06 and 1.05-1.33, respectively, P<0.05 or P<0.01). Conclusions: The patients with stage Ⅲ and Ⅳ pressure ulcers have a higher incidence of DVT on admission, with age and plasma D-dimer level being the independent risk factors for DVT of lower extremity. It is necessary to pay attention to the targeted screening of DVT and education of its prevention.

Common mtDNA variations at C5178a and A249d/T6392C/G10310A decrease the risk of severe COVID-19 in a Han Chinese population from Central China.

BACKGROUND: Mitochondria have been shown to play vital roles during severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and coronavirus disease 2019 (COVID-19) development. Currently, it is unclear whether mitochondrial DNA (mtDNA) variants, which define mtDNA haplogroups and determine oxidative phosphorylation performance and reactive oxygen species production, are associated with COVID-19 risk. METHODS: A population-based case-control study was conducted to compare the distribution of mtDNA variations defining mtDNA haplogroups between healthy controls (n = 615) and COVID-19 patients (n = 536). COVID-19 patients were diagnosed based on molecular diagnostics of the viral genome by qPCR and chest X-ray or computed tomography scanning. The exclusion criteria for the healthy controls were any history of disease in the month preceding the study assessment. MtDNA variants defining mtDNA haplogroups were identified by PCR-RFLPs and HVS-I sequencing and determined based on mtDNA phylogenetic analysis using Mitomap Phylogeny. Student's t-test was used for continuous variables, and Pearson's chi-squared test or Fisher's exact test was used for categorical variables. To assess the independent effect of each mtDNA variant defining mtDNA haplogroups, multivariate logistic regression analyses were performed to calculate the odds ratios (ORs) and 95% confidence intervals (CIs) with adjustments for possible confounding factors of age, sex, smoking and diseases (including cardiopulmonary diseases, diabetes, obesity and hypertension) as determined through clinical and radiographic examinations. RESULTS: Multivariate logistic regression analyses revealed that the most common investigated mtDNA variations (> 10% in the control population) at C5178a (in NADH dehydrogenase subunit 2 gene, ND2) and A249d (in the displacement loop region, D-loop)/T6392C (in cytochrome c oxidase I gene, CO1)/G10310A (in ND3) were associated with a reduced risk of severe COVID-19 (OR = 0.590, 95% CI 0.428-0.814, P = 0.001; and OR = 0.654, 95% CI 0.457-0.936, P = 0.020, respectively), while A4833G (ND2), A4715G (ND2), T3394C (ND1) and G5417A (ND2)/C16257a (D-loop)/C16261T (D-loop) were related to an increased risk of severe COVID-19 (OR = 2.336, 95% CI 1.179-4.608, P = 0.015; OR = 2.033, 95% CI 1.242-3.322, P = 0.005; OR = 3.040, 95% CI 1.522-6.061, P = 0.002; and OR = 2.890, 95% CI 1.199-6.993, P = 0.018, respectively). CONCLUSIONS: This is the first study to explore the association of mtDNA variants with individual's risk of developing severe COVID-19. Based on the case-control study, we concluded that the common mtDNA variants at C5178a and A249d/T6392C/G10310A might contribute to an individual's resistance to developing severe COVID-19, whereas A4833G, A4715G, T3394C and G5417A/C16257a/C16261T might increase an individual's risk of developing severe COVID-19.

LncRNA CASC2 inhibits lung adenocarcinoma progression through forming feedback loop with miR-21/p53 axis.

Lung adenocarcinoma (LUAD) is the most common type of lung cancer. Currently, the survival rate of LUAD patients remains low due to heterogeneity and high invasiveness. The long non-coding RNA (lncRNA) cancer susceptibility candidate 2 (CASC2) is reported to be related to LUAD development. Hence, we investigate the roles and regulatory mechanism of CASC2 in LUAD. The expression levels of CASC2, microRNA (miR)-21, and p53 were quantified by quantitative real-time polymerase chain reaction, and the protein levels of Bax, Bcl-2, p53, and p21 were examined using western blotting. A dual-luciferase reporter experiment was conducted to prove the molecular interactions between CASC2 and miR-21 or p53. CCK-8 and flow cytometry assays were conducted to assess cell proliferation and apoptosis, respectively. CASC2 was expressed at a low level in LUAD patients and LUAD cell lines. CASC2 overexpression markedly suppressed cell proliferation and enhanced apoptosis. Mechanistically, CASC2 overexpression dramatically inhibited miR-21 expression and increased p53 expression by directly targeting miR-21. Moreover, rescue experiments suggested that either miR-21 overexpression or p53 silencing obviously weakened the biological effects of CASC2 overexpression. In addition, p53 was proven to be an upstream transcription factor of CASC2 and can activate CASC2 transcription. These results provide evidence that the lncRNA CASC2/miR-21/p53 form a positive feedback loop to mediate cell proliferation and apoptosis in LUAD, which may provide a new insight into the pathological mechanisms of LUAD.

Does the Development of the Insurance Industry Promote the Purchase of Rural Commercial Health Insurance?

Deepening the reform of insurance companies and improving commercial insurance protection capabilities become issues important to national strategy. They involve improving China's multi-tiered social security system to analyze the deep-seated reasons impacting the purchasing behavior of commercial health insurance for rural residents in China. Using the DEA-CCR model, this paper evaluates the development of China's insurance industry, inspects the impact of insurance industry development on purchasing behavior of rural commercial health insurance based on the data of tracking survey projects from China's household, and carries out empirical analysis. The research result shows that the development of the insurance industry has obviously promoted the purchase behavior of commercial health insurance for rural residents. This research has significant practical value on protection and promotion of production and life quality of rural residents, which will also provide beneficial reference on the formulation and implementation of future operation strategy in China's commercial health insurance companies.

Can Physical Exercise Improve the Residents' Health?

With the rapid development of China's economy and society, the quality of life of residents has continued to improve, and the concept of health has gradually taken root in the hearts of the people. This paper uses the 2018 data of the China Family Panel Studies (CFPS) to analyze the internal mechanism and influencing factors of participating in physical exercise on the health level of residents. The results show that participating in physical exercise can significantly improve the subjective and objective health level of residents, and the result passed two important robustness tests. Heterogeneous test shows that the degree of influence of participation in physical exercise on the health level of residents varies according to the different regional and individual characteristics; the effect of urban residents' physical exercise to improve their health level is better than that of rural residents; and the effect of physical exercise on the improvement of health level is more obvious in the eastern and western areas, those who have not completed compulsory education, and those with high incomes. This study will have strong guiding significance for the improvement of the overall level of national health in China and will provide a theoretical basis and guiding opinions for the construction of healthy China.