Studying the impacts of variant evolution for a generalized age-group transmission model.

The differences of SARS-CoV-2 variants brought the changes of transmission characteristics and clinical manifestations during the prevalence of COVID-19. In order to explore the evolution mechanisms of SARS-CoV-2 variants and the impacts of variant evolution, the classic SIR (Susceptible-Infected-Recovered) compartment model was modified to a generalized SVEIR (Susceptible-Vaccinated-Exposed-Infected-Recovered) compartment model with age-group and varying variants in this study. By using of the SVEIR model and least squares method, the optimal fittings against the surveillance data from Fujian Provincial Center for Disease Control and Prevention were performed for the five epidemics of Fujian Province. The main epidemiological characteristics such as basic reproduction number, effective reproduction number, sensitivity analysis, and cross-variant scenario investigations were extensively investigated during dynamic zero-COVID policy. The study results showed that the infectivities of the variants became fast from wild strain to the Delta variant, further to the Omicron variant. Meanwhile, the cross-variant investigations showed that the average incubation periods were shortened, and that the infection scales quickly enhanced. Further, the risk estimations with the new variants were performed without implements of the non-pharmaceutical interventions, based on the dominant variants XBB.1.9.1 and EG.5. The results of the risk estimations suggested that non-pharmaceutical interventions were necessary on the Chinese mainland for controlling severe infections and deaths, and also that the regular variant monitors were still workable against the aggressive variant evolution and the emergency of new transmission risks in the future.

An SEIHR model with age group and social contact for analysis of Fuzhou COVID-19 large wave.

Background: The structure of age groups and social contacts of the total population influenced infection scales and hospital-bed requirements, especially influenced severe infections and deaths during the global prevalence of COVID-19. Before the end of the year 2022, Chinese government implemented the national vaccination and had built the herd immunity cross the country, and announced Twenty Measures (November 11) and Ten New Measures (December 7) for further modifications of dynamic zero-COVID polity on the Chinese mainland. With the nation-wide vaccination and modified measures background, Fuzhou COVID-19 large wave (November 19, 2022-February 9, 2023) led by Omicron BA.5.2 variant was recorded and prevailed for three months in Fujian Province. Methods: A multi-age groups susceptible-exposed-infected-hospitalized-recovered (SEIHR) COVID-19 model with social contacts was proposed in this study. The main object was to evaluate the impacts of age groups and social contacts of the total population. The idea of Least Squares method was governed to perform the data fittings of four age groups against the surveillance data from Fujian Provincial Center for Disease Control and Prevention (Fujian CDC). The next generation matrix method was used to compute basic reproduction number for the total population and for the specific age group. The tendencies of effective reproduction number of four age groups were plotted by using the Epiestim R package and the SEIHR model for in-depth discussions. The sensitivity analysis by using sensitivity index and partial rank correlation coefficients values (PRCC values) were operated to reveal the differences of age groups against the main parameters. Results: The main epidemiological features such as basic reproduction number, effective reproduction number and sensitivity analysis were extensively discussed for multi-age groups SEIHR model in this study. Firstly, by using of the next generation matrix method, basic reproduction number R0 of the total population was estimated as 1.57 using parameter values of four age groups of Fuzhou COVID-19 large wave. Given age group k, the values of R0k (age group k to age group k), the values of R0k (an infected of age group k to the total population) and the values of R^0k (an infected of the total population to age group k) were also estimated, in which the explorations of the impacts of age groups revealed that the relationship R0k>R0k>R^0k was valid. Then, the fluctuating tendencies of effective reproduction number Rt were demonstrated by using two approaches (the surveillance data and the SEIHR model) for Fuzhou COVID-19 large wave, during which high-risk group (G4 group) mainly contributed the infection scale due to high susceptibility to infection and high risks to basic diseases. Further, the sensitivity analysis using two approaches (the sensitivity index and the PRCC values) revealed that susceptibility to infection of age groups played the vital roles, while the numerical simulation showed that infection scale varied with the changes of social contacts of age groups. The results of this study claimed that the high-risk group out of the total population was concerned by the local government with the highest susceptibility to infection against COVID-19. Conclusions: This study verified that the partition structure of age groups of the total population, the susceptibility to infection of age groups, the social contacts among age groups were the important contributors of infection scale. The less social contacts and adequate hospital beds for high-risk group were profitable to control the spread of COVID-19. To avoid the emergence of medical runs against new variant in the future, the policymakers from local government were suggested to decline social contacts when hospital beds were limited.

Targeting macrophagic RasGRP1 with catechin hydrate ameliorates sepsis-induced multiorgan dysfunction.

BACKGROUND: The proinflammatory response induced by macrophages plays a crucial role in the development of sepsis and the resulting multiorgan dysfunction. Identifying new regulatory targets for macrophage homeostasis and devising effective treatment strategies remains a significant challenge in contemporary research. PURPOSE: This study aims to identify new regulatory targets for macrophage homeostasis and develop effective strategies for treating sepsis. STUDY DESIGN AND METHODS: Macrophage infiltration in septic patients and in lungs, kidneys, and brains of caecum ligation and puncture (CLP)-induced septic mice was observed using CIBERSORT and immunofluorescence (IF). Upon integrating the MSigDB database and GSE65682 dataset, differently expressed macrophage-associated genes (DEMAGs) were identified. Critical DEMAGs were confirmed through machine learning. The protein level of the critical DEMAG was detected in PBMCs of septic patients, RAW264.7 cells, and mice lungs, kidneys, and brains using ELISA, western blot, immunohistochemistry, and IF. siRNA was applied to investigate the effect of the critical DEMAG in RAW264.7 cells. A natural product library was screened to find a compound targeting the critical DEMAG protein. The binding of compounds and proteins was analyzed through molecular docking, molecular dynamics simulations, CETSA, and MST analysis. The therapeutic efficacy of the compounds against sepsis was then evaluated through in vitro and in vivo experiments. RESULTS: Macrophage infiltration was inversely correlated with survival in septic patients. The critical differentially expressed molecule RasGRP1 was frequently observed in the PBMCs of septic patients, LPS-induced RAW264.7 cells, and the lungs, kidneys, and brains of septic mice. Silencing RasGRP1 alleviated proinflammatory response and oxidative stress in LPS-treated RAW264.7 cells. Catechin Hydrate (CH) was identified as an inhibitor of RasGRP1, capable of maintaining macrophage homeostasis and mitigating lung, kidney, and brain damage during sepsis. CONCLUSION: This study demonstrates that RasGRP1, a novel activator of macrophage proinflammatory responses, plays a crucial role in the excessive inflammation and oxidative stress associated with sepsis. CH shows potential for treating sepsis by inhibiting RasGRP1.

QiShenYiQi pills preserve endothelial barrier integrity to mitigate sepsis-induced acute lung injury by inhibiting ferroptosis.

ETHNOPHARMACOLOGICAL RELEVANCE: The QiShengYiQi pill (QSYQ) is a traditional Chinese medicinal formulation. The effectiveness and safety of QSYQ in treating respiratory system disorders have been confirmed. Its pharmacological actions include anti-inflammation, antioxidative stress, and improving energy metabolism. However, the mechanism of QSYQ in treating sepsis-induced acute lung injury (si-ALI) remains unclear. AIM OF THE STUDY: Si-ALI presents a clinical challenge with high incidence and mortality rates. This study aims to confirm the efficacy of QSYQ in si-ALI and to explore the potential mechanisms, providing a scientific foundation for its application and insights for optimizing treatment strategies and identifying potential active components. MATERIALS AND METHODS: The impact of QSYQ on si-ALI was evaluated using the cecal ligation and puncture (CLP) experimental sepsis animal model. The effects of QSYQ on endothelial cells were observed through coculturing with LPS-stimulated macrophage-conditioned medium. Inflammatory cytokine levels, HE staining, Evans blue staining, lung wet/dry ratio, and cell count and protein content in bronchoalveolar lavage fluid were used to assess the degree of lung injury. Network pharmacology was utilized to investigate the potential mechanisms of QSYQ in treating si-ALI. Western blot and immunofluorescence analyses were used to evaluate barrier integrity and validate mechanistically relevant proteins. RESULTS: QSYQ reduced the inflammation and alleviated pulmonary vascular barrier damage in CLP mice (all P < 0.05). A total of 127 potential targets through which QSYQ regulates si-ALI were identified, predominantly enriched in the RAGE pathway. The results of protein-protein interaction analysis suggest that COX2, a well-established critical marker of ferroptosis, is among the key targets. In vitro and in vivo studies demonstrated that QSYQ mitigated ferroptosis and vascular barrier damage in sepsis (all P < 0.05), accompanied by a reduction in oxidative stress and the inhibition of the COX2 and RAGE (all P < 0.05). CONCLUSIONS: This study demonstrated that QSYQ maintains pulmonary vascular barrier integrity by inhibiting ferroptosis in CLP mice. These findings partially elucidate the mechanism of QSYQ in si-ALI and further clarify the active components of QSYQ, thereby providing a scientific theoretical basis for treating si-ALI with QSYQ.

Danlou tablet attenuates ischemic stroke injury and blood‒brain barrier damage by inhibiting ferroptosis.

ETHNOPHARMACOLOGICAL RELEVANCE: Danlou tablet (DLT) is a traditional Chinese medicinal formulation known for replenishing Qi, promoting blood circulation, and resolving stasis. Its pharmacological actions primarily involve anti-inflammatory, antioxidant stress reduction, antiapoptotic, proangiogenic, and improved energy metabolism. DLT has been confirmed to have favorable therapeutic effects on ischemic stroke (IS). However, the underlying mechanism through which DLT affects IS-induced brain injury remains unknown. AIM OF THE STUDY: This study aims to investigate the effects and underlying mechanisms of danlou tablet on ischemic stroke based on network pharmacology and experimental verification. MATERIALS AND METHODS: Using a transient middle cerebral artery occlusion (tMCAO) mouse model, the impact of DLT on the blood‒brain barrier (BBB) and brain injury in mice was assessed. Network pharmacology and bioinformatics analyses were utilized to explore the potential mechanisms of DLT in treating IS. Endothelial cells were cultured to observe the effects of DLT on vascular endothelial cells after oxygen-glucose deprivation/reperfusion, and these findings were validated in the brains of tMCAO mice. RESULTS: DLT alleviated oxidative stress and brain damage in tMCAO mice, mitigating BBB damage. A total of 185 potential targets through which DLT regulates IS were identified, including COX2, a known critical marker of ferroptosis, which identified as a key target. In vitro and in vivo experiments demonstrated that DLT significantly (p < 0.05) improved cell death and vascular barrier damage in IS, reducing intracellular oxidative stress and COX2 protein levels while increasing SLC7A11 and GPX4 protein levels. CONCLUSIONS: This study demonstrated that DLT maintained BBB integrity and alleviated brain injury of tMCAO mice by inhibiting ferroptosis. The study partially unraveled the mechanism through which DLT functioned in treating IS and further clarified the pivotal active components of DLT, thereby providing a theoretical scientific basis for treating IS with DLT.

Epidemic Characteristics, Spatiotemporal Pattern, and Risk Factors of Other Infectious Diarrhea in Fujian Province From 2005 to 2021: Retrospective Analysis.

BACKGROUND: Other infectious diarrhea (OID) continues to pose a significant public health threat to all age groups in Fujian Province. There is a need for an in-depth analysis to understand the epidemiological pattern of OID and its associated risk factors in the region. OBJECTIVE: In this study, we aimed to describe the overall epidemic characteristics and spatiotemporal pattern of OID in Fujian Province from 2005 to 2021 and explore the linkage between sociodemographic and environmental factors and the occurrence of OID within the study area. METHODS: Notification data for OID in Fujian were extracted from the China Information System for Disease Control and Prevention. The spatiotemporal pattern of OID was analyzed using Moran index and Kulldorff scan statistics. The seasonality of and short-term impact of meteorological factors on OID were examined using an additive decomposition model and a generalized additive model. Geographical weighted regression and generalized linear mixed model were used to identify potential risk factors. RESULTS: A total of 388,636 OID cases were recorded in Fujian Province from January 2005 to December 2021, with an average annual incidence of 60.3 (SD 16.7) per 100,000 population. Children aged <2 years accounted for 50.7% (196,905/388,636) of all cases. There was a steady increase in OID from 2005 to 2017 and a clear seasonal shift in OID cases from autumn to winter and spring between 2005 and 2020. Higher maximum temperature, atmospheric pressure, humidity, and precipitation were linked to a higher number of deseasonalized OID cases. The spatial and temporal aggregations were concentrated in Zhangzhou City and Xiamen City for 17 study years. Furthermore, the clustered areas exhibited a dynamic spreading trend, expanding from the southernmost Fujian to the southeast and then southward over time. Factors such as densely populated areas with a large <1-year-old population, less economically developed areas, and higher pollution levels contributed to OID cases in Fujian Province. CONCLUSIONS: This study revealed a distinct distribution of OID incidence across different population groups, seasons, and regions in Fujian Province. Zhangzhou City and Xiamen City were identified as the major hot spots for OID. Therefore, prevention and control efforts should prioritize these specific hot spots and highly susceptible groups.

Schizophrenia plausible protective effect of microRNA-137 is potentially related to estrogen and prolactin in female patients.

Background: Schizophrenia (SCZ) is a serious chronic mental disorder. Our previous case-control genetic association study has shown that microRNA-137 (miR-137) may only protect females against SCZ. Since estrogen, an important female sex hormone, exerts neuroprotective effects, the relationship between estrogen and miR-137 in the pathophysiology of SCZ was further studied in this study. Methods: Genotyping of single-nucleotide polymorphism rs1625579 of miR-137 gene in 1,004 SCZ patients and 896 healthy controls was conducted using the iMLDR assay. The effect of estradiol (E2) on the miR-137 expression was evaluated on the human mammary adenocarcinoma cell line (MCF-7) and the mouse hippocampal neuron cell line (HT22). The relationships between serum E2, prolactin (PRL), and peripheral blood miR-137 were investigated in 41 SCZ patients and 43 healthy controls. The miR-137 and other reference miRNAs were detected by real-time fluorescent quantitative reverse transcription-PCR. Results: Based on the well-known SNP rs1625579, the distributions of protective genotypes and alleles of the miR-137 gene were not different between patients and healthy controls but were marginally significantly lower in female patients. E2 upregulated the expression of miR-137 to 2.83 and 1.81 times in MCF-7 and HT22 cells, respectively. Both serum E2 and blood miR-137 were significantly decreased or downregulated in SCZ patients, but they lacked expected positive correlations with each other in both patients and controls. When stratified by sex, blood miR-137 was negatively correlated with serum E2 in female patients. On the other hand, serum PRL was significantly increased in SCZ patients, and the female patients had the highest serum PRL level and a negative correlation between serum PRL and blood miR-137. Conclusion: The plausible SCZ-protective effect of miR-137 may be female specific, of which the underlying mechanism may be that E2 upregulates the expression of miR-137. This protective mechanism may also be abrogated by elevated PRL in female patients. These preliminary findings suggest a new genetic/environmental interaction mechanism for E2/miR-137 to protect normal females against SCZ and a novel E2/PRL/miR-137-related pathophysiology of female SCZ, implying some new antipsychotic ways for female patients in future.

Visual analysis of the prevention and control measures of COVID-19 in Chinese ports.

In 2022, COVID-19 solutions in China have entered a normal stage, and the solutions imported from ports have been transformed from emergency prevention and control measures to investigative long-term prevention and control measures. Therefore, it is necessary to study solutions for COVID-19 at border ports. In this study, 170 research papers related to the prevention and control measures of COVID-19 at ports from 2020 to September 2022 were retrieved from Wanfang database, HowNet database, Wip database, and WoS core collection. Citespace 6.1.R2 software was used to research institutions visualize and analyze researchers and keywords to explore their research hotspots and trends. After analysis, the overall volume of documents issued in the past 3 years was stable. The major contributors are scientific research teams such as the Chinese Academy of Inspection and Quarantine Sciences (Han Hui et al.) and Beijing Customs (Sun Xiaodong et al.), with less cross-agency cooperation. The top five high-frequency keywords with cumulative frequency are as follows: COVID-19 (29 times), epidemic prevention and control (29 times), ports (28 times), health quarantine (16 times), and risk assessment (16 times). The research hotspots in the field of prevention and control measures for COVID-19 at ports are constantly changing with the progress of epidemic prevention and control. Cooperation between research institutions needs to be strengthened urgently. The research hotspots are the imported epidemic prevention and control, risk assessment, port health quarantine, and the normalized epidemic prevention and control mechanism, which is the trend of research and needs further exploration in the future.

Study of the influence of meteorological factors on HFMD and prediction based on the LSTM algorithm in Fuzhou, China.

BACKGROUND: This study adopted complete meteorological indicators, including eight items, to explore their impact on hand, foot, and mouth disease (HFMD) in Fuzhou, and predict the incidence of HFMD through the long short-term memory (LSTM) neural network algorithm of artificial intelligence. METHOD: A distributed lag nonlinear model (DLNM) was used to analyse the influence of meteorological factors on HFMD in Fuzhou from 2010 to 2021. Then, the numbers of HFMD cases in 2019, 2020 and 2021 were predicted using the LSTM model through multifactor single-step and multistep rolling methods. The root mean square error (RMSE), mean absolute error (MAE), mean absolute percentage error (MAPE) and symmetric mean absolute percentage error (SMAPE) were used to evaluate the accuracy of the model predictions. RESULTS: Overall, the effect of daily precipitation on HFMD was not significant. Low (4 hPa) and high (≥ 21 hPa) daily air pressure difference (PRSD) and low (< 7 °C) and high (> 12 °C) daily air temperature difference (TEMD) were risk factors for HFMD. The RMSE, MAE, MAPE and SMAPE of using the weekly multifactor data to predict the cases of HFMD on the following day, from 2019 to 2021, were lower than those of using the daily multifactor data to predict the cases of HFMD on the following day. In particular, the RMSE, MAE, MAPE and SMAPE of using weekly multifactor data to predict the following week's daily average cases of HFMD were much lower, and similar results were also found in urban and rural areas, which indicating that this approach was more accurate. CONCLUSION: This study's LSTM models combined with meteorological factors (excluding PRE) can be used to accurately predict HFMD in Fuzhou, especially the method of predicting the daily average cases of HFMD in the following week using weekly multifactor data.

Analysis of the volatile organic compounds of epidural analgesia-ameliorated metabolic disorder in pregnant women with gestational diabetes mellitus based on untargeted metabolomics.

Gestational diabetes mellitus (GDM) is a metabolic disease with an increasing annual incidence. Our previous observational study found that pregnant women with gestational diabetes had mild cognitive decline, which may be related to methylglyoxal (MGO). This study aimed to investigate whether labor pain aggravates the increase in MGO and explored the protective effect of epidural analgesia on metabolism in pregnant women with GDM based on solid-phase microextraction gas chromatography/mass spectrometry (SPME/GC-MS). Pregnant women with GDM were divided into a natural birth group (ND group, n = 30) and epidural analgesia group (PD group, n = 30). After fasting for ≥ 10 h overnight, venous blood samples were collected pre- and post-delivery to detect MGO, interleukin-6 (IL-6), and 8-epi-prostaglandin F2 alpha (8-iso-PGF2α) by ELISA. Serum samples were analyzed for volatile organic compounds (VOCs) using SPME-GC-MS. MGO, IL-6, and 8-iso-PGF2α levels in the ND group increased significantly post-delivery (P < 0.05) and were significantly higher in this group than the levels in the PD group (P < 0.05). Compared to the PD group, VOCs in the ND group increased significantly post-delivery. Further results indicated that propionic acid may be associated with metabolic disorders in pregnant women with GDM. Epidural analgesia can effectively improve the metabolism and immune function in pregnant women with GDM.

Study on the influence of meteorological factors on influenza in different regions and predictions based on an LSTM algorithm.

BACKGROUND: Influenza epidemics pose a threat to human health. It has been reported that meteorological factors (MFs) are associated with influenza. This study aimed to explore the similarities and differences between the influences of more comprehensive MFs on influenza in cities with different economic, geographical and climatic characteristics in Fujian Province. Then, the information was used to predict the daily number of cases of influenza in various cities based on MFs to provide bases for early warning systems and outbreak prevention. METHOD: Distributed lag nonlinear models (DLNMs) were used to analyse the influence of MFs on influenza in different regions of Fujian Province from 2010 to 2021. Long short-term memory (LSTM) was used to train and model daily cases of influenza in 2010-2018, 2010-2019, and 2010-2020 based on meteorological daily values. Daily cases of influenza in 2019, 2020 and 2021 were predicted. The root mean squared error (RMSE), mean absolute error (MAE), mean absolute percentage error (MAPE) and symmetric mean absolute percentage error (SMAPE) were used to quantify the accuracy of model predictions. RESULTS: The cumulative effect of low and high values of air pressure (PRS), air temperature (TEM), air temperature difference (TEMD) and sunshine duration (SSD) on the risk of influenza was obvious. Low (< 979 hPa), medium (983 to 987 hPa) and high (> 112 hPa) PRS were associated with a higher risk of influenza in women, children aged 0 to 12 years, and rural populations. Low (< 9 °C) and high (> 23 °C) TEM were risk factors for influenza in four cities. Wind speed (WIN) had a more significant effect on the risk of influenza in the ≥ 60-year-old group. Low (< 40%) and high (> 80%) relative humidity (RHU) in Fuzhou and Xiamen had a significant effect on influenza. When PRS was between 1005-1015 hPa, RHU > 60%, PRE was low, TEM was between 10-20 °C, and WIN was low, the interaction between different MFs and influenza was most obvious. The RMSE, MAE, MAPE, and SMAPE evaluation indices of the predictions in 2019, 2020 and 2021 were low, and the prediction accuracy was high. CONCLUSION: All eight MFs studied had an impact on influenza in four cities, but there were similarities and differences. The LSTM model, combined with these eight MFs, was highly accurate in predicting the daily cases of influenza. These MFs and prediction models could be incorporated into the influenza early warning and prediction system of each city and used as a reference to formulate prevention strategies for relevant departments.

Metabonomics fingerprint of volatile organic compounds in serum and urine of pregnant women with gestational diabetes mellitus.

BACKGROUND: Gestational diabetes mellitus (GDM) is a metabolic disease with an increasing annual incidence rate. Our previous observational study found that pregnant women with GDM had mild cognitive decline. AIM: To analyze the changes in metabonomics in pregnant women with GDM and explore the mechanism of cognitive function decline. METHODS: Thirty GDM patients and 30 healthy pregnant women were analyzed. Solid-phase microextraction gas chromatography/mass spectrometry was used to detect organic matter in plasma and urine samples. Statistical analyses were conducted using principal component analysis and partial least squares discriminant analysis. RESULTS: Differential volatile metabolites in the serum of pregnant women with GDM included hexanal, 2-octen-1-ol, and 2-propanol. Differential volatile metabolites in the urine of these women included benzene, cyclohexanone, 1-hexanol, and phenol. Among the differential metabolites, the conversion of 2-propanol to acetone may further produce methylglyoxal. Therefore, 2-propanol may be a potential marker for serum methylglyoxal. CONCLUSION: 2-propanol may be a potential volatile marker to evaluate cognitive impairment in pregnant women with GDM.

Identification of the key ferroptosis-related genes involved in sepsis progression and experimental validation in vivo.

Background: Ferroptosis has a vital role in sepsis, but the mechanism is not known. Understanding the mechanism of ferroptosis during sepsis will aid in developing improved therapeutic strategies. Methods: We used the Gene Expression Omnibus database and FerrDb database to obtain ferroptosis-related differentially expressed genes (DEGs) between sepsis patients and healthy volunteers (HVs). Analyses of PPI networks, functional enrichment, as well as use of the MCODE algorithm were used to identify key ferroptosis-related DEGs. Expression of key ferroptosis-related DEGs was verified using: GSE57065 and GSE65682 datasets; rats in which ferroptosis was induced with erastin; sepsis-induced acute lung injury (siALI) rats. The effects of acupoint catgut embedding (ACE) on ferroptosis and expression of key ferroptosis-related DEGs in the lungs of siALI rats were also observed. A Cox proportional hazard model was used to verify the effect of key ferroptosis-related DEGs on the survival of sepsis patients. Cytoscape was used to construct ceRNA networks and gene-transcription factor networks. Results: Between sepsis patients and HVs, we identified 33 ferroptosis-related DEGs. According to analyses of PPI networks and the MCODE algorithm, we obtained four modules, of which the most significant module contained nine ferroptosis-related DEGs. Functional-enrichment analyses showed that four of the nine DEGs were enriched in the MAPK signaling pathway: MAPK14, VEGFA, TGFBR1, and DUSP1. We verified expression of these four genes in GSE57065 and GSE65682 datasets and ferroptosis rats. In addition, expression of these four genes and that of the oxidative-stress indicators GSSG and MDA was upregulated, and glutathione peroxidase-4 (GPX4) expression was downregulated, in siALI rats, but ACE reversed these changes. The Cox proportional hazard model showed that survival of sepsis patients in the high-risk group was shorter than that in the low-risk group. We found that the XIST-hsa-let-7b-5p-TGFBR1/DUSP1 ceRNA network and transcription factor E2F1 may be important regulators of these four DEGs. Conclusion: Our results suggest that MAPK14, VEGFA, TGFBR1, and DUSP1 may be key regulatory targets of ferroptosis in sepsis, and that ACE pretreatment may be antioxidant treatment for sepsis and alleviate ferroptosis. These findings provide a basis for further ferroptosis-related study in sepsis and provide new targets for its treatment.

Genome analysis of human respiratory syncytial virus in Fujian Province, Southeast China.

BACKGROUND: Respiratory syncytial virus (RSV) is one of the main causes of acute respiratory infections (ARI) leading to a heavy disease burden. Reports on RSV in China are limited, especially in Fujian Province, and RSV whole-genome sequences in Fujian Province are not reported. This study aimed to explore the genomic characteristics of RSV to provide evidence for the development of vaccines and medicines. METHODS: Reverse transcription-polymerase chain reaction (RT-PCR) was used to amplify and obtain the attachment (G) gene and whole-genome fragments from the positive samples. Genetic evolution as well as nucleotide and amino acid homology analyses of the virus sequences were conducted to identify any amino acid mutations. RESULTS: A total of 72 RSV-positive cases were collected, and 53 G gene sequences were obtained using polymerase chain reaction (PCR) amplification. The ON1 and BA11 genotypes were found to be dominant using the Basic Local Alignment Search Tool (BLAST) on the NCBI website. The 40 genotype ON1 sequences had high nucleotide identity (95.3%-99.8%) and amino acid similarity (92.5%-100%), whereas the 13 BA11 genotype sequenceshad 97.3% - 99.6% nucleotide identity and 94.8% - 99.7% amino acid similarity. Compared to the ON1 prototype (JN257693) and BA11 prototype (AY333364), the obtained sequences had no nucleotide insertions or deletions, indicating high similarity among the samples. A total of 17 RSV whole genome sequences were obtained, 10 of which were genotype ON1 and seven were genotype BA11. Certain amino acid mutations were found in the antigen site and epitope of the fusion (F) protein but not in the G protein. Glycosylation analyses of specific RSV genes revealed high positive selection rates for the gene, and the N- and O-linked glycosylation sequences in the F gene were relatively conserved. CONCLUSIONS: From July 2018 to January 2020, ON1 and BA11 were the most prevalent RSV genotypes in Fujian Province. A high nucleotide identity and amino acid similarity were observed between the reference strain and the obtained strains, as well as among the sequences of the obtained isotypes. Certain amino acid mutations occur at the antigen site and the epitope of the F protein.

Case Report: A Deletion Variant in the DCAF17 Gene Underlying Woodhouse-Sakati Syndrome in a Chinese Consanguineous Family.

Woodhouse-Sakati syndrome (WSS, MIM 241080) is a rare neuroendocrine disease characterized by hair loss, hypogonadism, diabetes, hearing loss, and extrapyramidal syndrome, and is usually caused by mutations in the DCAF17 gene as an inherited disease. DCAF17 plays an important role in mammalian gonadal development and infertility. So far, there have been no WSS reports in China. The patient introduced in this case is from a consanguineous family. The main symptoms of the patient were alopecia and gonadal agenesis. Other symptoms such as hearing loss, intellectual disability, and hyperglycemia were remarkable, and these symptoms are often observed in WSS patients. We found a nonsense mutation in the 11th exon of the gene DCAF17 (Refseq: NM_025000) in the patient and her younger brother, which confirmed the diagnosis of WSS. The genetic results also showed that the mutation was inherited from their healthy first-cousin parents.

Diagnostic significance of serum PP4R1 and its predictive value for the development of chronic complications in patients with type 2 diabetes mellitus.

BACKGROUND: Protein phosphatase 4 regulatory subunit 1 (PP4R1) is one of the regulatory subunits of PP4. It has been determined to be involved in the regulation of TNF-α-induced hepatic insulin resistance and gluconeogenesis. Considering the important role of PP4R1 in hepatic insulin resistance, the current study explored the expression and diagnostic value of PP4R1 in type 2 diabetes mellitus (T2DM) patients and further investigated its predictive value for the development of chronic complications. METHOD: Hundred and five patients with T2DM and 97 healthy controls were collected. qRT-PCR was used for the measurement of serum PP4R1 mRNA level in both T2DM and control groups. The diagnostic value of PP4R1 in T2DM patients was evaluated using receiver operating characteristic (ROC) curve. Kaplan-Meier methods and Cox regression analysis were used to evaluate the predictive value of PP4R1 for the development of chronic complications in T2DM patients. RESULTS: PP4R1 was determined to be elevated in the serum of T2DM patients compared with healthy controls. Serum PP4R1 had the potential to distinguish T2DM patients from healthy controls with a sensitivity of 81.9% and specificity of 82.5%. Patients with high PP4R1 expression experienced more chronic complications events. The multivariate Cox analysis results suggested that serum PP4R1 expression was an independent factor for the occurrence of chronic complications for T2DM patients.  CONCLUSION: PP4R1 is elevated in the serum of T2DM patients, had the potential to distinguish T2DM patients from healthy controls. PP4R1 serves as a promising biomarker for predicting the risk of future chronic complications in T2DM patients.

Early diagnosis of breast cancer from exhaled breath by gas chromatography-mass spectrometry (GC/MS) analysis: A prospective cohort study.

BACKGROUND: It has proved that there is an association between cancer and volatile organic compounds (VOCs) of exhaled breath. This study targets on verifying the existence of specific VOCs in breathing in breast cancer patients, especially those with ductal carcinoma in situ (DCIS). METHODS: There were a total of 203 participants included in the final analysis, which included 71 (35.0%) patients with histologically confirmed breast cancer (including 13 with DCIS, 31 with lymph node metastasis-negative status, and 27 with lymph node metastasis-positive status), 78 (38.4%) healthy volunteers, and 54 (26.6%) patients with histologically confirmed gastric cancer. Gas chromatography-mass spectrometry and solid-phase microextraction were used to analyze the breath samples for the presence of VOCs. RESULTS: There were significant differences in the volatile organic metabolites between the DCIS, lymph node metastasis-negative breast cancer, and lymph node metastasis-positive breast cancer groups compared with the healthy controls as well as between the breast cancer and gastric cancer patients. An overlapping set of seven VOCs, including (S)-1,2-propanediol, cyclopentanone, ethylene carbonate, 3-methoxy-1,2-propanediol, 3-methylpyridine, phenol, and tetramethylsilane, was significantly different between the breast cancer patients and healthy individuals as well as between the breast cancer and gastric cancer patients. The combination of these seven compounds was considered as a biomarker for breast cancer. The sensitivity for predicting DCIS by this set of seven compounds was determined to be 80.77%, and the specificity was determined to be 100%. CONCLUSIONS: This set of seven breast cancer-specific VOCs can be regarded as one particular expiratory marker for DCIS and will help to establish new screening methods for early breast cancer.

Treatment strategies for Graves' ophthalmopathy: a network meta-analysis.

PURPOSE: Various treatments have been investigated for Graves' ophthalmopathy (GO). We aimed to provide an overall profile of the efficacy and tolerability of various interventions for active and moderate to severe GO. METHODS: PubMed, Embase and the Cochrane Central Register of Controlled Trials were searched on 6 July 2018. Randomised controlled trials (RCT) investigating GO treatments were included. Two researchers independently extracted data according to a predefined form. A random effects network meta-analysis was performed using a frequentist approach. The primary outcome was efficacy, and the secondary outcome was tolerability (side effect discontinuation). RESULTS: Thirty-three studies with 1846 patients with GO were included. Orbital radiotherapy (ORT) plus intravenous glucocorticoids (IVGC) (OR 27.11; 95% CI 4.57 to 160.92), mycophenolate mofetil (MMF) (24.40, 95% CI 5.28 to 112.67), oral glucocorticoids (OGC) plus ciclosporin (20.22, 95% CI 1.60 to 255.20), IVGC plus MMF (12.08, 95% CI 2.96 to 49.35), teprotumumab (8.92, 95% CI 2.51 to 31.77), ORT plus OGC (4.88, 95% CI 1.25 to 19.06), rituximab (RTX) (4.85, 95% CI 1.18 to 19.86), somatostatin analogues (4.23, 95% CI 1.60 to 11.16), OGC plus azathioprine (AzA) (5.77, 95% CI 1.17 to 28.47) and IVGC (4.96, 95% CI 1.96 to 12.55) showed significantly better improvement than no treatment. ORT plus IVGC ranked first, followed by MMF. High heterogeneity and significant local inconsistency were observed in the RTX studies. The results of the sensitivity analyses were similar to those of the main analysis. CONCLUSION: A robust recommendation regarding the best treatment cannot be made, because most evidence was rated as low or very low quality according to the Grading of Recommendations, Assessment, Development and Evaluations framework. Large RCTs and individual participant data meta-analyses are necessary to confirm these results and explore potential moderators. PROPERO TRIAL REGISTRATION NUMBER: CRD42018103029.

Chinese massage combined with core stability exercises for nonspecific low back pain: a randomized controlled trial.

OBJECTIVE: To determine the effect of Chinese massage combined with core stability exercises on nonspecific low back pain. METHODS: In the prospective study, ninety-two participants with nonspecific low back pain were divided into experimental and control group at random, and 46 in each. The experimental group were treated using Chinese massage combined with core stability exercises, while the control group were treated using Chinese massage alone. The two groups were evaluated using visual analog scale and Oswestry disability index at baseline, immediately after two and eight weeks. In addition, the recurrence rate of nonspecific low back pain was evaluated one year after the last intervention. RESULTS: Two weeks after treatment, both VAS and ODI scores decreased significantly in two groups (p<0.05), when compared with the values before treatment, but no difference between the two groups (p>0.05). Eight weeks later, the VAS and ODI scores decreased significantly in both groups (p<0.05); at the same time, both VAS and ODI scores were significantly lower (p<0.05) in the experimental group than those in the control group. At the final follow-up, five cases recurred in the experimental group and nineteen cases in the control group, the control group has a significantly higher recurrence rate (p<0.05). CONCLUSION: Core stability exercises can improve the therapeutic effect of Chinese massage in treating nonspecific low back pain.