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Background Cardiovascular disease is a major chronic disease that seriously endangers human health, and remains a public health problem to be solved in China and even globally. Objective To explore the epidemic characteristics and disease burden of cardiovascular diseases in China from 1990 to 2019, forecast the incidence of cardiovascular diseases in China from 2020 to 2050, and provide a reference for the formulation of relevant prevention and treatment strategies of cardiovascular diseases. Methods The 2019 Global Burden of Disease Study (GBD 2019) database was searched to extract and analyze relevant data on cardiovascular disease burden and risk factors in China and globally from 1990 to 2019. The prevalence of cardiovascular diseases was quantified by using the publicly available incidence, prevalence, mortality, and corresponding age-standardized rate (referred to as standardized rate) based on GBD 2019 database, and the burden of diseases was quantified by years lived with disability (YLD), years of life lost (YLL) and disability adjusted life year (DALY), and the ARIMA model was constructed to predict the incidence of cardiovascular diseases in China from 2020 to 2050. Results Compared with 1990, the incidence, prevalence and mortality of cardiovascular diseases in China showed an increasing trend by year up to 2019, in which the incidence, prevalence and mortality increased by 93.75%, 99.75% and 57.39%, respectively. The standardized incidence and prevalence of females were higher than those of males, while the standardized mortality was lower than that of males (P

Abstract. Severe asthma is “asthma which requires treatment with high dose inhaled corticosteroids (ICS) plus a second controller (and/or systemic corticosteroids) to prevent it from becoming ‘uncontrolled’ or which remains ‘uncontrolled’ despite this therapy.” The state of control was defined by symptoms, exacerbations and the degree of airflow obstruction. Therefore, for the diagnosis of severe asthma, it is important to have evidence for a diagnosis of asthma with an assessment of its severity, followed by a review of comorbidities, risk factors, triggers and an assessment of whether treatment is commensurate with severity, whether the prescribed treatments have been adhered to and whether inhaled therapy has been properly administered. Phenotyping of severe asthma has been introduced with the definition of a severe eosinophilic asthma phenotype characterized by recurrent exacerbations despite being on high dose ICS and sometimes oral corticosteroids, with a high blood eosinophil count and a raised level of nitric oxide in exhaled breath. This phenotype has been associated with a Type-2 (T2) inflammatory profile with expression of interleukin (IL)-4, IL-5, and IL-13. Molecular phenotyping has also revealed non-T2 inflammatory phenotypes such as Type-1 or Type-17 driven phenotypes. Antibody treatments targeted at the T2 targets such as anti-IL5, anti-IL5Rα, and anti-IL4Rα antibodies are now available for treating severe eosinophilic asthma, in addition to anti-immunoglobulin E antibody for severe allergic asthma. No targeted treatments are currently available for non-T2 inflammatory phenotypes. Long-term azithromycin and bronchial thermoplasty may be considered. The future lies with molecular phenotyping of the airway inflammatory process to refine asthma endotypes for precision medicine.

Student Dropout Prediction (SDP) is pivotal in mitigating withdrawals in Massive Open Online Courses. Previous studies generally modeled the SDP problem as a binary classification task, providing a single prediction outcome. Accordingly, some attempts introduce survival analysis methods to achieve continuous and consistent predictions over time. However, the volatility and sparsity of data always weaken the models' performance. Prevailing solutions rely heavily on data pre-processing independent of predictive models, which are labor-intensive and may contaminate authentic data. This paper proposes a Survival Analysis based Volatility and Sparsity Modeling Network (SAVSNet) to address these issues in an end-to-end deep learning framework. Specifically, SAVSNet smooths the volatile time series by convolution network while preserving the original data information using Long-Short Term Memory Network (LSTM). Furthermore, we propose a Time-Missing-Aware LSTM unit to mitigate the impact of data sparsity by integrating informative missingness patterns into the model. A survival analysis loss function is adopted for parameter estimation, and the model outputs monotonically decreasing survival probabilities. In the experiments, we compare the proposed method with state-of-the-art methods in two real-world MOOC datasets, and the experiment results show the effectiveness of our proposed model.

Objective In this study, we investigated the association between comorbid sleep apnoea–hypopnoea syndrome (SAHS) and the prognosis of patients in an intensive care unit (ICU) to determine whether this relationship varies between different disease subgroups.Methods We conducted a retrospective cohort study using publicly available information from the critical care database Medical Information Mart for Intensive Care III. Adults (≥18 years of age) who attended the ICU for the first time were enrolled. Demographic information and clinical data were obtained from each patient. The primary outcome was 30-day mortality after ICU admission, and the secondary outcomes were in-hospital and ICU mortality. Multivariate logistic regression and Cox regression analyses were used to examine the associations between SAHS comorbidities and the research outcomes. Propensity score matching was used to adjust for potential confounding variables.Results Of the 32 989 patients enrolled, 1918 (5.81%) were diagnosed with SAHS as a comorbid condition. Patients with SAHS had a significantly lower 30-day mortality rate compared with those without SAHS (5.27% vs 13.65%, respectively; p

Abstract Src homology 2 domain-containing protein tyrosine phosphatase 2 (SHP-2) is a cytoplasmic tyrosine phosphatase that is highly expressed in hematopoietic cells and in the CNS and exerts opposite effects on signal transduction by exerting a neuroprotective or proapoptotic effect. Several mutations of SHP-2 have been found in children with myeloproliferative disorders or malignant leukemia, and some of these can affect brain development. In the present study, we aimed to identify and functionally characterize genetic variations in SHP-2 in 72 preterm and 58 full-term infants and to evaluate the effect of the variations on neurodevelopment in preterm infants. Twelve genetic variations were identified. Among them, two variations in the SHP-2 promoter, g.-317C > T and g.-273G > A, were found to significantly increase promoter activity, and the frequency of g.-273G > A was higher in preterm infants than in full-term infants. Two transcription factors, NF-κB and GABPα, were found to be involved in the transcriptional regulation of SHP-2 by the two above-mentioned variations. In particular, we found that g.-273G > A was significantly associated with delayed myelination and poor motor development in preterm infants. Our results suggest that a functional promoter variation in SHP-2 is associated with spontaneous preterm birth itself as well as white matter myelination and neurodevelopment.

Our previous studies revealed molecular alterations of tumor vessels, varying from immature to mature alterations, resulting from Abraxane, and demonstrated that the integrin-specific PET tracer 18F-FPPRGD2 can be used to noninvasively monitor such changes. However, changes in the tumor vasculature at functional levels such as perfusion and permeability are also important for monitoring Abraxane treatment outcomes in patients with cancer. The purpose of this study is to further investigate the vascular response during Abraxane therapy and the effectiveness of its synergistic interaction with cisplatin using Dynamic contrast enhanced-magnetic resonance imaging (DCE-MRI). Thirty MDA-MB-435 tumor mice were randomized into three groups: PBS control (C group), Abraxane only (A group), and sequential treatment with Abraxane followed by cisplatin (A-P group). Tumor volume was monitored based on caliper measurements. A DCE-MRI protocol was performed at baseline and day 3. The Ktrans, Kep and Ve were calculated and compared with CD31, α-SMA, and Ki67 histology data. Sequential treatment with Abraxane followed by cisplatin produced a significantly greater inhibition of tumor growth during the three weeks of the observation period. Decreases in Ktrans and Kep for the A and A-P groups were observed on day 3. Immunohistological staining suggested vascular remodeling during the Abraxane therapy. The changes in Ktrans and Kep values were correlated with alterations in the permeability of the tumor vasculature induced by the Abraxane treatment. In conclusion, Abraxane-mediated permeability variations in tumor vasculature can be quantitatively visualized by DCE-MRI, making this a useful method for studying the effects of early cancer treatment, especially the early vascular response. Vascular remodeling by Abraxane improves the efficiency of cisplatin delivery and thus results in a favorable treatment outcome.

Social support has been widely known as a protective factor for the emotional well-being (EWB) of older adults, but less studies have investigated the roles of different sources of social support (i.e., family and friend support) on different facets of EWB (i.e., positive affect and negative affect) simultaneously.In this study, the associations between family/friend support and positive/negative affect were investigated in a sample of 700 Chinese elderly. The EWB and social support were measured with a 12-item affective wordlist (Kahneman et al., 2004) and a self-prepared questionnaire. The results showed that (1) the order of contact frequency and mutual support followed a hierarchical order from spouse, children, to friends; (2) zero-order correlations of both family support and friend support were associated with more positive affect and less negative affect; and when compared with the relative role of family and friend support, (3) spouse (children if spouse is not available) support had greater contribution on decreasing negative affect, while friend support had greater influence on increasing positive affect, even after controlling the demographic, self-rated health and life events variables.Family and friend support play different roles on the two facets of EWB of the elderly. These results were better explained in light of the task specificity model rather than the hierarchical compensatory model. Moreover, positive affect may be enhanced by friend support (based on personal interests and selectable) rather than family support (bonded by kinship and not selectable), which added evidences to the socioemotional selectivity theory.

Melanocyte-specific CD8(+) cytotoxic T lymphocytes (CTLs) play a pivotal role in vitiligo-induced depigmentation. Yet, the mechanisms underlying the high frequency of generalized autoimmune disorders associated with generalized vitiligo (GV) are unknown. We hypothesized that an imbalance between activated CD8(+) CTLs and regulatory T cells (Tregs) exists in patients with GV . Assessment of the circulating CD8(+) CTLs and Tregs by flow cytometric analysis revealed an obvious expansion of CD8(+) CTLs and a concomitant decrease in Treg cells in GV patients. The percentages of skin infiltrating CD8(+) CTLs and Tregs were evaluated by immunohistochemistry and revealed dramatically increased numbers of both CD8(+) CTLs and Tregs in the perilesional skin of GV patients. However, peripheral Tregs were impaired in their ability to suppress the proliferation and cytolytic capacity of autologous CD8(+) T cells, suggesting that a functional failure of Tregs and the hyper-activation of CD8(+) CTLs may contribute to progressive GV. Our data indicate that reduced numbers and impaired function of natural Tregs fail to control the widespread activation of CD8(+) CTLs, which leads to the destruction of melanocytes and contributes to the elevated frequency of various associated autoimmune diseases. This knowledge furthers our understanding of the mechanisms of immune tolerance that are impaired in GV patients and may aid in the future development of effective immunotherapy for GV patients.

Abstract Background Despite the high cure rate of differentiated thyroid cancer (DTC), patients endure side effects from treatment and psychological distress, impacting their quality of life. The potential of mobile health (mHealth) interventions to address these issues remains unexplored. The purpose of this study is to develop an mHealth intervention based on the Multi-Theoretical Model of Health Behavior Change (MTM) and evaluate its impact on reducing anxiety, depression, fear of cancer progression, and enhancing quality of life in DTC patients. Methods A single-blind, single-center, prospective, randomized controlled trial was conducted. One hundred and eleven consecutive DTC patients from Harbin Medical University’s Fourth Hospital were enrolled from March 2023 to March 2024. Participants were randomized into a control group and an intervention group that received a 3-month mHealth intervention based on MTM theory. Outcomes were assessed using web-based questionnaires at baseline and conclusion. Results One hundred four patients with DTC completed the study, with 7 lost to follow-up (6.3%). The intervention group experienced a significant drop in PHQ-4 scores post-MTM-mHealth intervention (P

Abstract Background Aberrant accumulation of R-loops leads to DNA damage, genome instability and even cell death. Therefore, the timely removal of harmful R-loops is essential for the maintenance of genome integrity. Nucleolar R-loops occupy up to 50% of cellular R-loops due to the frequent activation of Pol I transcription. However, the mechanisms involved in the nucleolar R-loop resolution remain elusive. The nucleolar acetyltransferase NAT10 harbors a putative RecD helicase domain (RHD), however, if NAT10 acts in the R-loop resolution is still unknown. Methods NAT10 knockdown cell lines were constructed using CRISPR/Cas9 technology and short hairpin RNA targeting NAT10 mRNA, respectively. The level of R-loops was detected by immunofluorescent staining combined with RNase H treatment. The helicase activity of NAT10 or DDX21 was determined by in vitro helicase experiment. The interaction between NAT10 and DDX21 was verified by co-immunoprecipitation, immunofluorescent staining and GST pull-down experiments. Acetylation sites of DDX21 by NAT10 were analyzed by mass spectrometry. NAT10 knockdown-induced DNA damage was evaluated by immunofluorescent staining and Western blot detecting γH2AX. Results Depletion of NAT10 led to the accumulation of nucleolar R-loops. NAT10 resolves R-loops through an RHD in vitro and in cells. However, Flag-NAT10 ∆RHD mutant still partially reduced R-loop levels in the NAT10-depleted cells, suggesting that NAT10 might resolve R-loops through additional pathways. Further, the acetyltransferase activity of NAT10 is required for the nucleolar R-loop resolution. NAT10 acetylates DDX21 at K236 and K573 to enhance the helicase activity of DDX21 to unwind nucleolar R-loops. The helicase activity of DDX21 significantly decreased by Flag-DDX21 2KR and increased by Flag-DDX21 2KQ in cells and in vitro. Consequently, NAT10 depletion-induced nucleolar R-loop accumulation led to DNA damage, which was rescued by co-expression of Flag-DDX21 2KQ and Flag-NAT10 G641E, demonstrating that NAT10 resolves nucleolar R-loops through bipartite pathways. Conclusion We demonstrate that NAT10 is a novel R-loop resolvase and it resolves nucleolar R-loops depending on its helicase activity and acetylation of DDX21. The cooperation of NAT10 and DDX21 provides comprehensive insights into the nucleolar R-loop resolution for maintaining genome stability.

ObjectiveTo explore the prevalence and influencing factors of multimorbidity among the HIV-infected individuals receiving anti-viral therapy (ART) in Dehong Prefecture of Yunnan Province, so as to provide a reference for the long-term follow-up management of HIV-infected patients and the comprehensive prevention and treatment of chronic diseases.MethodsA cross-sectional study was conducted to investigate the multimorbidity burden among the HIV-infected adults receiving ART in Dehong Prefecture from January to July 2021 and a self-designed questionnaire was used to analyze relevant disease indicators. Multivariate logistic regression analysis was used to investigate the influencing factors of multimorbidity among the HIV-infected individuals.ResultsA total of 3 946 HIV-infected individuals receiving ART were enrolled in this study, of which 63.7% aged ≤50 years, with a male to female ratio of 1.1∶1. Among the 3 946 cases, 825 of them had ≥2 comorbidities, with a co-prevalence rate of 20.9% (95%CI:19.6%‒22.2%), and the main comorbidities were dyslipidemia, diabetes, and hypertension. Multivariate logistic regression analysis showed that 40≤ aged

ObjectiveTo explore the influence of "Internet plus" postpartum health care service on postpartum depression, and to provide an evidence for reducing the incidence of postpartum depression and improving the quality of life for postnatal women.MethodsMothers who gave birth between August 1, 2021 and June 30, 2023 lived in the six streets of Xuhui District were selected as the research subjects. The puerperants were randomly divided into the intervention group and the control group according to the order of enrollment using a numerical numbering system, with 210 cases in each of the intervention group and control group. The intervention group adopted the "Internet plus" postpartum health care services, while the control group adopted the conventional postpartum health care services. The risk factors related to postpartum mental health and the incidence of postpartum depression were compared between the two groups.ResultsThere was no statistically significant difference in the scores of postpartum mental health-related risk factors between the two groups at the first 2 weeks and 1st month after delivery (t=0.736 and t=1.260, P>0.05). However, there was a statistically significant difference in the scores of postpartum mental health-related risk factors at the 3rd months after delivery and 6th months after delivery (t=2.089, P0.05). In the 1st month, the 3rd month and the 6th month after delivery, the intervention group adopted the "Internet plus" postpartum health care service, thus the differences in depression scores were statistically significant (t=2.616, t=2.793 and t=3.107, P

Relevance. Aging is anatural biological process of aretrograde nature, during which there is an imbalance of all systems, including the matrix metalloproteinase (MMP) system and tissue inhibitors of matrix metalloproteinases (TIMP). And vascular aging is associated with functional and structural changes primarily in the arterial vasculature with age. Aging may be atrigger factor for pathological changes in the endothelium. The molecular mechanisms underlying the process of vascular endothelial dysfunction include increased expression and activation of matrix metalloproteinases, the concentration of which changes with aging. Numerous studies report the role of MMP-1,–2,–9,–12 in the pathogenesis of premature aging of the endothelium; they initiate cell apoptosis, which contributes to increased permeability, but there are no studies in which all age categories of both men and women were analyzed, not burdened by somatic pathology. This study examines the features of the proteolysis/antiproteolysis system in apparently healthy people of different ages and genders.Materials and Methods.As part of the pilot study, 347 apparently healthy people took part (226 women and 121 men, divided by age, according to the WHO classification), who underwent the first stage of clinical examination at the State Budgetary Institution “Consultative and Diagnostic Center of the Mountains. Yuzhno-­Sakhalinsk”, in which the level of MMP and TIMP in the blood serum was determined by solid-­phase ELISA, ng/ml. Statistical processing of the research results was carried out using the IBM SPSS Statistics Version 25.0 software package.Resultsand Discussion.Changes in the proteolysis/antiproteolysis system were determined in both agroup of men and women of different ages, which can be characterized as not pathological, but close to such. It was found that in men aged 60-74 years, discoordinated work of matrix metalloproteinases and their inhibitors was recorded in the direction of enhancing the profibrosing effect, and in women in the same age category, the exact opposite component was identified—anti-fibrosing.Conclusion.The current development has demonstrated the influence of age and genetic resources on the system of matrix metalloproteinases and their tissue inhibitors, in addition, aspecial age group has been identified—the elderly group, which requires protection of the vascular system in order to monitor the impaired proteolysis/antiproteolysis system.

Abstract Disulfidptosis, the newest form of programmed cell death, is closely associated with the immune microenvironment of cancer cells. Long non-coding RNA (lncRNA) has also been found to play a crucial role in melanoma. However, the role of disulfidptosis-related lncRNA in melanoma remains unclear. Through bioinformatic analysis of the transcriptional, clinical, and pathological data from the TCGA-SKCM (The Cancer Genome Atlas—Skin cutaneous melanoma) database, we established a 2-Disulfidptosis-related lncRNA (DRL) prognostic model and a novel molecular subtype for melanoma. The survival and ROC curves of the 2-DRL prognostic model demonstrated its strong efficacy in predicting the prognosis of melanoma. The high-risk group of melanoma exhibited a significant decrease in ESTIMATEScore, ImmuneScore, and StromalScore, indicative of pronounced immune suppression and exhaustion. Subgroup C2 of melanoma displayed an immune-activated state, while subgroups C1 and C3 showed immune suppression and exhaustion, potentially leading to poorer prognosis. Subgroup C1 demonstrated better sensitivity to Zoledronate, UMI-77, Nilotinib, and Cytarabine. Subgroup C2 exhibited greater sensitivity to Ribociclib, XAV939, Topotecan, and Ruxolitinib. Subgroup C3 showed higher sensitivity to VX-11e, Ulixertinib, Trametinib, and Afatinib. This study revealed the immune microenvironment status and targeted drug sensitivity in melanoma patients with different risk scores and molecular subtypes, offering valuable guidance for clinical treatment and identifying significant DRL targets for future in-depth research.

The Guangdong Province Laboratory Animals Ordinance (the GPLAO), officially enacted and implemented in October 2010, marked a new phase of legal management in the administration of laboratory animals in Guangdong Province. The GPLAO clearly authorizes the laboratory animal monitoring institutes in Guangdong Province to conduct laboratory animal quality monitoring and assume corresponding legal responsibilities. It also specifies the standards for the production and use of laboratory animals, while bringing attention to laboratory animal welfare and ethics. Through the formulation of supporting documents, the active promotion of the standardization and regulation of administrative law enforcement, and the implementation of measures to delegate power, streamline administration, and optimize government services, significant improvements have been made in the standardized management of laboratory animals in Guangdong Province and in supporting the innovative development of biomedicine. Moreover, notable achievements have been made in areas such as the construction of experimental animal technology platforms, standardization work, the preservation and development of unique resources, and talent pool development. However, with the advancements in science and technology, social economy, and legislative work, some aspects in the GPLAO have been identified for improvement. These include the need for clearer provisions on laboratory animal welfare, more specific guidelines for the management of genetically engineered animals, improved regulations on the safety and welfare of practitioners, further refined implementation of the "one-vote veto system", continued promotion of laboratory animal standardization, and the exploration of effective mechanisms for resource sharing. This paper reviews and summarizes the institutional characteristics, post-legislation implementation, and effectiveness of the GPLAO, as well as the issues and countermeasures identified during the implementation. It concludes the laboratory animals management practices in Guangdong Province during the past 10 years, aiming to provide a reference for laboratory animal legislation.

Objective To cultivate and breed laboratory cats in conventional laboratory animal facilities, collect background data on laboratory cats, and compare them with purchased domestic cats to assess the feasibility of breeding laboratory cats. Methods Indigenous cat breeds were introduced for reproduction and population expansion under conventional laboratory environment, with recording of kitten survival rates and growth curves. Indicators of 20 laboratory cats of F1 generation (half male and half female), including complete blood count, blood biochemistry, organ mass, organ coefficient, heart rate, and blood pressure, were detected and comparisons between sexes were made. Blood pressure values and sensitivity to histamine of these cats were measured using depressor substance detection method in the Pharmacopoeia of the People's Republic of China-Four Parts: 2020, and were compared with the data from 173 concurrently purchased domestic cats. Results Laboratory cats adapted well to the environment of conventional laboratory facilities, with a survival rate of 77.08% of kittens at 8 weeks of age. Red blood cell count, hemoglobin content, mean corpuscular hemoglobin concentration, and hematocrit in male laboratory cats were significantly higher than those in females (P0.05). Compared to laboratory cats, purchased domestic cats had significantly higher heart rate, systolic pressure, and mean blood pressure (P

Abstract Biochar-supported ZVI have received increasing attention for their potential to remove nitrobenzene in groundwater and soil. However, the capacity of this material to enhance the biological reduction of nitrobenzene and alter microbial communities in anaerobic groundwater have not been explored. In this study, the nitrobenzene removal performance and mechanism of modified biochar-supported zerovalent iron (ZVI) composites were explored in anaerobic soil. The results showed that the 700 °C biochar composite enhanced the removal of nitrobenzene and inhibited its release from soil to the aqueous phase. NaOH-700-Fe50 had the highest removal rate of nitrobenzene, reaching 64.4%. However, the 300 °C biochar composite inhibited the removal of nitrobenzene. Microbial degradation rather than ZVI-mediated reduction was the main nitrobenzene removal pathway. The biochar composites changed the richness and diversity of microbial communities. ZVI enhanced the symbiotic relationship between microbial genera and weakened competition between soil microbial genera. In summary, the 700 °C modified biochar composite enhanced the removal of nitrobenzene by increasing microbial community richness and diversity, by upregulating functional genes, and by promoting electron transfer. Overall, the modified biochar-supported ZVI composites could be used for soil remediation, and NaOH-700-Fe50 is a promising composite material for the on-site remediation of nitrobenzene-contaminated groundwater.

Cerebrovascular diseases pose a serious threat to human health. According to the latest epidemiological data, stroke is one of the leading causes of death and disability among adults worldwide. Acute ischemic stroke (AIS), which is caused by local circulatory disorders in the brain, accounts for over 80% of all strokes and is the most common type of stroke. Due to extensive damage to the cerebral cortex or direct involvement of the autonomic nerve centers and pathways caused by AIS, the balance between the sympathetic and parasympathetic nervous systems is disturbed (with a predominance of sympathetic activation). Therefore, the organs targeted by the downstream pathways of the sympathetic and parasympathetic nervous systems are affected by the neurotransmitters they secrete, resulting in a range of systemic complications (such as cardiac complications, stroke-related infections, gastrointestinal complications, acute kidney injury, metabolic changes, and sexual dysfunction). These systemic pathological changes, in turn, affect the progression of AIS, thereby exacerbating brain damage or directly leading to patient death. Treatments targeting imbalances in the autonomic nervous system may play a role in reducing complications and improving the prognosis of AIS. This article reviews the systemic effects of autonomic dysfunction following AIS and its mechanisms, providing insights for the treatment of AIS and intervention of systemic complications.

ObjectiveTo carry out an epidemiological analysis on an outbreak of Mycoplasma pneumoniae infection at a welfare institution to provide a theoretical basis for the corresponding prevention and control measures.MethodsUsing the method of field epidemiological investigation， special field treatment was carried out in September 2022. Serum samples from cases and close contacts in the same ward area were collected for detection of nine respiratory tract infection pathogens （Mycoplasma pneumoniae， chlamydia， influenza， human metapneumosis， respiratory syncytial， human boca， parainfluenza type 1‒4 virus， and Middle East respiratory syndrome， severe acute respiratory syndrome coronavirus） by immunofluorescence immunoglobulin M （IgM） antibody test.ResultsA total of 14 Mycoplasma pneumoniae cases were identified， all of whom were residents of the welfare institution. The first case occurred on September 4， while the last case was reported on September 13. The incidence rate of the fifth ward area where the first case reported was 12.82% （10/78）， and it was 3.57% （3/84） in the third ward area and 1.20% （1/83） in the first ward area. There was a significant difference in incidence rates between ward areas （χ2=8.90， P

Abstract Genotoxic therapy triggers reactive oxygen species (ROS) production and oxidative tissue injury. S-nitrosylation is a selective and reversible posttranslational modification of protein thiols by nitric oxide (NO), and 5,6,7,8-tetrahydrobiopterin (BH4) is an essential cofactor for NO synthesis. However, the mechanism by which BH4 affects protein S-nitrosylation and ROS generation has not been determined. Here, we showed that ionizing radiation disrupted the structural integrity of BH4 and downregulated GTP cyclohydrolase I (GCH1), which is the rate-limiting enzyme in BH4 biosynthesis, resulting in deficiency in overall protein S-nitrosylation. GCH1-mediated BH4 synthesis significantly reduced radiation-induced ROS production and fueled the global protein S-nitrosylation that was disrupted by radiation. Likewise, GCH1 overexpression or the administration of exogenous BH4 protected against radiation-induced oxidative injury in vitro and in vivo. Conditional pulmonary Gch1 knockout in mice (Gch1 fl/fl ; Sftpa1-Cre +/− mice) aggravated lung injury following irradiation, whereas Gch1 knock-in mice (Gch1 lsl/lsl ; Sftpa1-Cre +/− mice) exhibited attenuated radiation-induced pulmonary toxicity. Mechanistically, lactate dehydrogenase (LDHA) mediated ROS generation downstream of the BH4/NO axis, as determined by iodoacetyl tandem mass tag (iodoTMT)-based protein quantification. Notably, S-nitrosylation of LDHA at Cys163 and Cys293 was regulated by BH4 availability and could restrict ROS generation. The loss of S-nitrosylation in LDHA after irradiation increased radiosensitivity. Overall, the results of the present study showed that GCH1-mediated BH4 biosynthesis played a key role in the ROS cascade and radiosensitivity through LDHA S-nitrosylation, identifying novel therapeutic strategies for the treatment of radiation-induced lung injury.

Abstract The biological mechanisms triggered by low-dose exposure still need to be explored in depth. In this study, the potential mechanisms of low-dose radiation when irradiating the BEAS-2B cell lines with a Cs-137 gamma-ray source were investigated through simulations and experiments. Monolayer cell population models were constructed for simulating and analyzing distributions of nucleus-specific energy within cell populations combined with the Monte Carlo method and microdosimetric analysis. Furthermore, the 10 × Genomics single-cell sequencing technology was employed to capture the heterogeneity of individual cell responses to low-dose radiation in the same irradiated sample. The numerical uncertainties can be found both in the specific energy distribution in microdosimetry and in differential gene expressions in radiation cytogenetics. Subsequently, the distribution of nucleus-specific energy was compared with the distribution of differential gene expressions to guide the selection of differential genes bioinformatics analysis. Dose inhomogeneity is pronounced at low doses, where an increase in dose corresponds to a decrease in the dispersion of cellular-specific energy distribution. Multiple screening of differential genes by microdosimetric features and statistical analysis indicate a number of potential pathways induced by low-dose exposure. It also provides a novel perspective on the selection of sensitive biomarkers that respond to low-dose radiation.

COVID-19 sequelae are long-term symptoms of COVID-19. Cardiovascular disease is not only a risk factor for the occurrence of COVID-19 sequelae but also a potential result directly or indirectly caused by COVID-19 infection.

Since the identification of the poliovirus in 1908, over a hundred serotypes of enteroviruses have been discovered, capable of causing a range of diseases including hand, foot, and mouth disease, newborn sepsislike syndrome, aseptic meningitis, acute flaccid paralysis, respiratory disorders, and acute hemorrhagic conjunctivitis. In recent years, enteroviruses such as EV-A71 and EV-D68 have exhibited globalized periodic outbreaks, emerging as a significant and indisputable challenge in the field of public health. However, the current preventive and control measures for enteroviruses remain notably limited, necessitating a pressing need to delve deeper into the molecular mechanisms responsible for enteroviral pathogenesis. This will facilitate the development of novel targets and methodologies for the creation of effective, safe, and broad-spectrum antiviral drugs. This comprehensive review focuses on the classification, epidemiology, structure, life cycle, interplay between viral proteins and host factors, pathogenic mechanisms, clinical treatments, and the establishment and application of animal infection models relevant to enteric viruses. The aim is to serve as a theoretical referential basis for the prevention and control of enteroviruses, offering novel perspectives for the development of drugs and the establishment of a vaccine repository dedicated to combating enteroviruses.

Antisense oligonucleotides(ASOs) are a novel class of small molecule gene-targeted drugs that can bind with target mRNA. Through complementary base pairing with the target sequence, antisense oligonucleotides achieve targeted regulation of genes. With the continuous development of gene sequencing technology and molecular synthesis techniques, research and applications of ASOs in the musculoskeletal system have further advanced. This article reviews the mechanisms of ASOs in gene silencing and expression regulation, as well as their prospects in gene therapy. It also evaluates the research progress and applications of ASOs in musculoskeletal diseases and analyzes the urgent issues currently faced by this class of drugs. This comprehensive study aims to deepen our understanding of ASOs and provide valuable reference for their widespread application in biomedical research and clinical settings.

ObjectiveTo conduct comprehensive assessment of internal and external cadmium exposure and health risks for Shanghai residents.MethodsCadmium levels in food samples were calculated by employing two dietary exposure assessment methods， total diet study （TDS） and food frequency questionnaire （FFQ）， to estimate the daily dietary cadmium exposure of Shanghai residents. The provisional tolerable monthly intake （PTMI） of cadmium set by joint food and agriculture organization/WHO expert committee on food additives （JECFA） was applied to evaluate the health risk. Differences in dietary and urinary cadmium were compared by rank-sum test among different regions， age， gender， smoking status， and BMI groups， and the association between internal and external cadmium exposure was investigated by correlation analysis.ResultsThe mean value of urinary cadmium for 1 300 respondents was 0.542 μg·L-1. Urinary cadmium was higher in the population in central urban and urban-rural fringe areas than in the suburban area， higher in the older age group than in the younger age group， and higher in the smoking group than in the non-smoking group （all P

Objective To explore the effect of esketamine on working memory impairment in neuropathic mice and its underlying mechanism. Methods Fifty clean grade male C57BL/6J mice (2 months) were divided into 5 groups by random number table method: sham+saline (SN group), CCI+saline (CN group), CCI+esketamine(CE group), CCI+ANA-12 (CA group), CCI+ANA-12+esketamine (CAE group), with 10 mice in each group. Chronic constriction injury (CCI) was employed to establish a neuropathic pain model. On the 16th day after modeling, CE group and CAE group were administered ketamine (10 mg/kg), CAE group received ANA-12 (0.5 mg/kg) half an hour before ketamine injection, CA group was only given ANA-12, and SN group and CN group received an equivalent volume of saline. The administration was done through intraperitoneal injection for 5 consecutive days. The open-field test (OFT), paw withdrawal threshold (PWT), paw withdrawal latency (PWL) and Y-maze test were performed from day 21 after surgery. Bromo-2-deoxyUridine (BrdU) was dissolved in saline and intraperitoneally injected into the mice on days 21 to 23 after the surgery. Western blot was performed to determine the expression of Brain-derived neurotrophic factor(BDNF) in hippocampus, the immunofluorescence was performed to determine the number of BrdU and doublecortxin (DCX) positive cells in the dentate gyrus (DG) area of hippocampal. Results Compared with SN group, the other four groups showed significant reductions in both PWT and PWL on day 21 after surgery (all P

Risk assessment models for periodontal disease provide dentists with a precise and consolidated evaluation of the prognosis of periodontitis, enabling the formulation of personalized treatment plans. Periodontal risk assessment systems have been widely applied in clinical practice and research. The application fields of periodontal risk assessment systems vary based on the distinctions between clinical periodontal parameters and risk factors. The assessment models listed below are commonly used in clinical practice, including the periodontal risk calculator (PRC), which is an individual-based periodontal risk assessment tool that collects both periodontal and systemic information for prediction; the periodontal assessment tool (PAT), which allows for quantitative differentiation of stages of periodontal disease; the periodontal risk assessment (PRA) and modified periodontal risk assessment (mPRA), which are easy to use; and the classification and regression trees (CART), which assess the periodontal prognosis based on a single affected tooth. Additionally, there are orthodontic-periodontal combined risk assessment systems and implant periapical risk assessment systems tailored for patients needing multidisciplinary treatment. This review focuses on the current application status of periodontal risk assessment systems.

This study aimed to evaluate the efficacy and safety of solid organ transplantation recipients inoculated with an inactivated COVID-19 vaccine.