Indomethacin restrains cytoplasmic nucleic acid-stimulated immune responses by inhibiting the nuclear translocation of IRF3.

The recognition of cytosolic nucleic acid triggers the DNA/RNA sensor-IRF3 axis-mediated production of type I interferons (IFNs), which are essential for antiviral immune responses. However, the inappropriate activation of these signaling pathways is implicated in autoimmune conditions. Here, we report that indomethacin, a widely used nonsteroidal anti-inflammatory drug, inhibits nucleic acid-triggered IFN production. We found that both DNA- and RNA-stimulated IFN expression can be effectively blocked by indomethacin. Interestingly, indomethacin also prohibits the nuclear translocation of IRF3 following cytosolic nucleic acid recognition. Importantly, in cell lines and a mouse model of Aicardi-Goutières syndrome, indomethacin administration blunts self-DNA-induced autoimmune responses. Thus, our study reveals a previously unknown function of indomethacin and provides a potential treatment for cytosolic nucleic acid-stimulated autoimmunity.

[Chemical constituents from Alangium chinense subsp. pauciflorum].

Chemical constituents of 70% ethanol extract of Alangium chinense subsp. pauciflorum were investigated. The 70% ethanol extract of A. chinense subsp. pauciflorum was isolated and purified by D-101 macroporous resins, silica gel, Sephadex LH-20 and other methods. As a result, nineteen compounds were isolated and identified as 4-cyclohexene-1α,2α,3α-triol-1-O-ß-D-glucoside(1), 1ß,4α,6α,13-tetrahydroxy-eudesm-11(12)-ene(2), sucrose(3), 1'-O-benzyl-α-L-rhamnopyranosyl-(1″→6')-ß-D-glucopyranoside(4), bis(2-ethylhexyl)benzene-1,2-dicarboxylate(5),(Z)-10-heneicosenoic acid(6), di-O-methylcrenati(7), methyl-α-D-fructofuranoside(8), ß-daucosterol(9), syringic acid(10), vanillicacid(11), octacosanol(12), isoarborinol(13), 2,7-dihydroxy-6-methyl-4-(1-methylethyl)-1-naphthalenecarboxylate(14),vanillin(15), coniferyl aldehyde(16), 9(11)-dehydroergosterolperoxide(17), 5α,8α-epidioxy-(22E,24R)-ergosta-6,22-dien-3ß-ol(18), ß-sitosterol(19), respectively. Compounds 1 and 2 were new compounds, compounds 5-11, 13, 15-18 were isolated from Alangium for the first time.The anti-inflammatory activity of compourd 1 was determinded by the LPS-induced RAW264.7 macrophage inflammation model. The results showed that the new compound 1 has a certain inhibitory effect on LPS-induced NO production of RAW264.7 cells, and the inhibitory rate was 54.57%.

Achalasia Following SARS-CoV-2 Infection: A Case Report and Review of Literature.

RATIONALE: The COVID-19 pandemic caused by the SARS-CoV-2 virus has led to health complications beyond respiratory symptoms, revealing multi-organ involvement, including potential gastrointestinal implications. PATIENT CONCERNS: We present a case of a 40-year-old female without any history of achalasia who developed symptoms of the condition following a confirmed SARS-CoV-2 infection. Unusually, multiple esophageal ulcers were identified, which are not typically associated with achalasia. DIAGNOSIS: Achalasia and esophageal ulcers were confirmed through a series of examinations, including barium swallow, CT scan, and upper endoscopy. Furthermore, immunohistochemical staining of esophageal biopsy specimens revealed the presence of the SARS-CoV-2 spike protein, suggesting direct viral involvement. INTERVENTIONS: The patient was treated with calcium channel blockers and proton pump inhibitors and later underwent a peroral endoscopic myotomy (POEM) procedure following the resolution of her COVID-19 infection. OUTCOME: After the POEM procedure, the patient made a good recovery. LESSONS: This case underscores the potential for SARS-CoV-2 to trigger gastrointestinal complications and emphasizes the need for ongoing patient management and further research into the long-term implications of COVID-19. Despite the single-case nature of this report, it contributes to the expanding understanding of the diverse and multi-systemic impact of COVID-19.

The Janus face of HIF-1α in ischemic stroke and the possible associated pathways.

Stroke is the most devastating disease, causing paralysis and eventually death. Many clinical and experimental trials have been done in search of a new safe and efficient medicine; nevertheless, scientists have yet to discover successful remedies that are also free of adverse effects. This is owing to the variability in intensity, localization, medication routes, and each patient's immune system reaction. HIF-1α represents the modern tool employed to treat stroke diseases due to its functions: downstream genes such as glucose metabolism, angiogenesis, erythropoiesis, and cell survival. Its role can be achieved via two downstream EPO and VEGF strongly related to apoptosis and antioxidant processes. Recently, scientists paid more attention to drugs dealing with the HIF-1 pathway. This review focuses on medicines used for ischemia treatment and their potential HIF-1α pathways. Furthermore, we discussed the interaction between HIF-1 and other biological pathways such as oxidative stress; however, a spotlight has been focused on certain potential signaling contributed to the HIF-1 pathway. HIF-1 is an essential regulator of oxygen balance within cells which affects and controls the expression of thousands of genes related to sustaining homeostasis as oxygen levels fluctuate. HIF-1α's role in ischemic stroke strongly depends on the duration and severity of brain damage after onset. HIF-1 remains difficult to investigate, particularly in ischemic stroke, due to alterations in the acute and chronic phases of the disease, as well as discrepancies between the penumbra and ischemic core. This review emphasizes these contrasts and analyzes the future of this intriguing and demanding field.

Assessing health-related quality of life of Chinese population using CQ-11D.

PURPOSE: This study aimed to assess the health-related quality of life (HRQoL) of the Chinese population by using the Chinese medicine quality of life-11 dimensions (CQ-11D) questionnaire and to identify factors associated with HRQoL. METHODS: The data was derived from a survey conducted by the Institute of Pharmacoeconomics Evaluation at Beijing University of Chinese Medicine on the quality of life of the Chinese population. The sex and age of respondents were considered through quota sampling. Demographic, socioeconomic, and health indicators were collected using the structured questionnaire. We performed bivariate analyses first to examine the associations between the above factors and the HRQoL of respondents measured by the CQ-11D. Multivariate linear regression and ordinal logistic regression models were established to analyze the factors (demographic, socioeconomic, and health indicators) differences in HRQoL, as well as the risk of each group reporting problems across the 11 dimensions of CQ-11D. RESULTS: From February 2021 to November 2022, a total of 7,604 respondents were involved and 7,498 respondents were included. The sample approximated the general adult Chinese population in terms of age, sex, and district of residence, and each geographic distribution ranged from 9.71 to 25.54%. Of the respondents, 45.84% were male, and 89.82% were Han ethnicity. The mean utility score ranged from 0.796 to 0.921 as age increased. According to the respondents, most health problems were identified in the PL (fatigue) (70.16%) and SM (quality of sleep) (63.63%) dimensions. The CQ-11D index scores varied with the demographic and socioeconomic characteristics of respondents, except for ethnicity (p > 0.05) and income (p > 0.05). The multivariate analysis revealed significant negative associations between health utility scores and various factors. These factors include sex (female), age over 65, belonging to ethnic minorities, rural household registration, being widowed or divorced, having a primary school education or below, being a student or unemployed, having a low income of 0-1,300, engaging in smoking or drinking, limited participation in physical activities, experiencing changes in self-perceived health status compared to the previous year, and having chronic diseases. The odds of respondents reporting problems in 11 dimensions varied among different socio-demographic groups. CONCLUSIONS: This study reports the first Chinese population norms for the CQ-11D derived using a representative sample of the Chinese general population. Self-reported health status measured by the CQ-11D varies among different socio-economic groups. In addition to participation a physical activity and the presence of chronic disease, smoking and drinking also significantly influence HRQoL.

Lactobacillus rhamnosus GG ameliorates hyperuricemia in a novel model.

Hyperuricemia (HUA) is a metabolic syndrome caused by abnormal purine metabolism. Although recent studies have noted a relationship between the gut microbiota and gout, whether the microbiota could ameliorate HUA-associated systemic purine metabolism remains unclear. In this study, we constructed a novel model of HUA in geese and investigated the mechanism by which Lactobacillus rhamnosus GG (LGG) could have beneficial effects on HUA. The administration of antibiotics and fecal microbiota transplantation (FMT) experiments were used in this HUA goose model. The effects of LGG and its metabolites on HUA were evaluated in vivo and in vitro. Heterogeneous expression and gene knockout of LGG revealed the mechanism of LGG. Multi-omics analysis revealed that the Lactobacillus genus is associated with changes in purine metabolism in HUA. This study showed that LGG and its metabolites could alleviate HUA through the gut-liver-kidney axis. Whole-genome analysis, heterogeneous expression, and gene knockout of LGG enzymes ABC-type multidrug transport system (ABCT), inosine-uridine nucleoside N-ribohydrolase (iunH), and xanthine permease (pbuX) demonstrated the function of nucleoside degradation in LGG. Multi-omics and a correlation analysis in HUA patients and this goose model revealed that a serum proline deficiency, as well as changes in Collinsella and Lactobacillus, may be associated with the occurrence of HUA. Our findings demonstrated the potential of a goose model of diet-induced HUA, and LGG and proline could be promising therapies for HUA.

Observational retrospective clinical study on clinical features of macrolide-resistant Mycoplasma pneumoniae pneumonia in Chinese pediatric cases.

This study aimed to investigate differences in clinical characteristics and laboratory findings between children infected with Macrolide-Sensitive Mycoplasma pneumoniae (MSMP) and Macrolide-Resistant Mycoplasma pneumoniae (MRMP). Additionally, the research sought to identify laboratory markers for rapidly distinguishing refractory Mycoplasma pneumoniae pneumonia (RMPP) from ordinary Mycoplasma pneumoniae pneumonia (OMPP). In total, 265 Mycoplasma pneumoniae (MP) patients were included, with MRMP identified by specific point mutations in domain V of the 23S rRNA gene. A retrospective analysis compared the clinical courses and laboratory data, revealing that MRMP patients experienced prolonged febrile days (P = 0.004), elevated CRP levels (P < 0.001), and higher MP DNA loads than MSMP patients (P = 0.037). Based on clinical symptoms, MRMP was divided into RMPP (n = 56) and OMPP (n = 70), with RMPP demonstrating significantly increased IL-18, community-acquired respiratory distress syndrome (CARDS) toxins in nasopharyngeal aspirate, and serum CRP levels (P < 0.001; P = 0.006; P < 0.001). In conclusion, timely recognition of RMPP is crucial for enhancing prognosis. The identification of MRMP, coupled with proinflammatory cytokines such as IL-18, CARDS toxins, and CRP, emerges as promising markers with the potential to contribute significantly to diagnostic accuracy and prognosis assessment.

Association of serum concentrations of remnant cholesterol with incident cardiovascular disease in patients with rheumatoid arthritis: A real-world data from 2001 to 2022.

BACKGROUND: Remnant cholesterol (RC) promotes cardiovascular disease (CVD) in the general population, but its role among rheumatoid arthritis (RA) patients remains unknown. We aimed to investigate circulating RC levels associated with incident CVD among Chinese patients with RA. METHODS: A total of 1018 RA patients free of baseline CVD were included and followed up in a prospective RA CVD cohort from 2001 to 2022. Fasting serum levels of triglycerides, total cholesterol (TC), low-density (LDL-C), and high-density lipoprotein cholesterol (HDL-C) were measured, while RC and Non-HDL-C levels were calculated. The primary exposure was RC levels. A LASSO Cox model was used to select covariates. The Fine-Gray competing risk model was used to estimate hazard ratios (HRs). RESULTS: RA patients had a mean age of 53.9 years, and 802 (78.8%) were females. After a median follow-up of 5.54 years, 131 patients developed CVD with an incidence rate of 21.6 per 1000 person-years. Continuous and quartile-categorized RC levels were associated with incident CVD before and after multivariate adjustment and Bonferroni correction (all P < 0.001). There were no robust associations of other lipids with incident CVD. The fully adjusted HRs for RC were 2.30 (95% CI 1.58-3.35) per 1 mmol/L increase, and 2.40 (1.36-4.25) and 2.81 (1.60-4.94) for patients in the 3rd and 4th versus the 1st quartile, respectively. CONCLUSIONS: Circulating RC levels are positively associated with incident CVD among Chinese RA patients independent of known risk factors, implying its clinically preferable use for improving the stratification of CVD risk in RA patients.

In-house ammonia induced lung impairment and oxidative stress of ducks.

Ammonia (NH3) is a toxic gas that in intensive poultry houses, damages the poultry health and induces various diseases. This study investigated the effects of NH3 exposure (0, 15, 30, and 45 ppm) on growth performance, serum biochemical indexes, antioxidative indicators, tracheal and lung impairments in Pekin ducks. A total of 288 one-day-old Pekin male ducks were randomly allocated to 4 groups with 6 replicates and slaughtered after the 21-d test period. Our results showed that 45 ppm NH3 significantly reduced the average daily feed intake (ADFI) of Pekin ducks. Ammonia exposure significantly reduced liver, lung, kidney, and heart indexes, and lowered the relative weight of the ileum. With the increasing of in-house NH3, serum NH3 and uric acid (UA) concentrations of ducks were significantly increased, as well as liver malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione peroxidase (GPX-Px) contents. High NH3 also induced trachea and lung injury, thereby increasing levels of tumor necrosis factor-α (TNF-α) and interleukin-4 (IL-4) in the lung, and decreasing the mRNA expressions of zonula occludens 1 (ZO-1) and claudin 3 (CLDN3) in the lung. In conclusion, in-house NH3 decrease the growth performance in ducks, induce trachea and lung injuries and meanwhile increase the compensatory antioxidant activity for host protection.

Design and application of a novel "turn-on" fluorescent probe for imaging sulfite in living cells and inflammation models.

Sulfite is one of the main existing forms of sulfur dioxide (SO2) in living system, which has been recognized as an endogenous mediator in inflammation. Evidence has accumulated to show that abnormal level of sulfite is associated with many inflammatory diseases, including neurological diseases and cancers. Herein, a novel fluorescent probe named QX-OA was designed and synthesized to detect sulfite. QX-OA was constructed by choosing quinolinium-xanthene as the fluorophore and levulinate as the specific and relatively steady recognition reaction. The probe showed remarkable green turn-on signal at 550 nm, together with high sensitivity (90-fold) and excellent selectivity to sulfite over other possible interfering species. In the meantime, QX-OA was successfully applied to visualize endogenous and exogenous sulfite in Hela cells. In the LPS-induced inflammation model, QX-OA could visualize the dose-dependent increase of sulfite level (0-2 mg/mL). Consequently, QX-OA was determined to be a potential method for detecting sulfite in pre-clinical diagnosis.

Geriatric nutrition risk index: a more powerful index identifying muscle mass loss in patients with rheumatoid arthritis.

OBJECTIVE: To explore the association of geriatric nutrition risk index (GNRI), a traditional albumin-body weight calculation, with myopenia in patients with rheumatoid arthritis (RA) and compare its ability to identify myopenia with protein indicators. METHODS: This cross-sectional study was carried out based on a Chinese RA cohort. Clinical data and protein indicators (including albumin, globulin, albumin to globulin ratio, prealbumin, hemoglobin) were collected. GNRI was estimated by serum albumin and body weight. Myopenia was indicated as muscle mass loss measured by bioelectric impedance analysis. RESULTS: There were 789 RA patients included with mean age 52.6 ± 12.6 years and 77.6% female. There were 41.3%, 18.0%, 27.5%, 13.2% patients with no (GNRI > 98), low (GNRI 92 to ≤ 98), moderate (GNRI 82 to < 92), and major nutrition-related risk (GNRI < 82). There were 406 (51.5%) RA patients with myopenia, RA patients with major nutrition-related risk had the highest prevalence of myopenia (87.5% vs. 73.3% vs. 50.0% vs. 26.1%). Multivariate logistic analysis showed that compared with no risk, RA patients with low (OR = 3.23, 95% CI: 1.86-5.61), moderate (OR = 9.56, 95% CI: 5.70-16.01), and major nutrition-related risk (OR = 28.91, 95% CI: 13.54-61.71) were associated with higher prevalence of myopenia. Receiver operating characteristic curves showed that GNRI (AUC = 0.79) performed a better identifiable ability toward myopenia than serum albumin (AUC = 0.66) or others indicators (AUC range 0.59 to 0.65), respectively. CONCLUSION: GNRI, an objective and convenient albumin-weight index, may be preferable for identifying myopenia in RA patients. Key Points • We firstly elucidated the association of GNRI with muscle mass loss among RA patients, and compared its ability to identify muscle mass loss with serum albumin or other protein indicators. • Major nutrition-related risk identified by GNRI showed the highest risk of muscle mass loss, GNRI demonstrated a greater ability to identify myopenia in RA patients. which indicated GNRI was an objective and convenient albumin-weight index to identify myopenia in RA patients.

Pre- and intra-operative risk factors predict postoperative respiratory failure after minimally invasive oesophagectomy.

OBJECTIVES: Severe pulmonary complications such as postoperative respiratory failure can occur after minimally invasive oesophagectomy. However, the risk factors have not been well identified. The goal of this study was to develop a predictive model for the occurrence of postoperative respiratory failure with a large sample. METHODS: We collected data from patients with oesophageal cancer who had a minimally invasive oesophagectomy at Shanghai Chest Hospital from 2019 to 2022. Univariable and backward stepwise logistic regression analysis of 19 pre- and intra-operative factors was used before model fitting, and its performance was evaluated with the receiver operating characteristic curve. Internal validation was assessed with a calibration plot, decision curve analysis and area under the curve with 95% confidence intervals, obtained from 1000 resamples set by the bootstrap method. RESULTS: This study enrolled 2,386 patients, 57 (2.4%) of whom developed postoperative respiratory failure. Backward stepwise logistic regression analysis revealed that age, body mass index, cardiovascular disease, diabetes, diffusion capacity of the lungs for carbon monoxide, tumour location and duration of chest surgery ≥101.5 min were predictive factors. A predictive model was constructed and showed acceptable performance (area under the curve: 0.755). The internal validation with the bootstrap method proves the good agreement for prediction and reality. CONCLUSIONS: Obesity, severe diffusion dysfunction and upper segment oesophageal cancer were strong predictive factors. The established predictive model has acceptable predictive validity for postoperative respiratory failure after minimally invasive oesophagectomy, which may improve the identification of high-risk patients and enable health-care professionals to perform risk assessment for postoperative respiratory failure at the initial consultation.

Population pharmacokinetic/pharmacodynamic modeling of H018, a selective JAK1 inhibitor, in healthy Chinese volunteers.

H018 is an orally administered, selective, small-molecule inhibitor of Janus kinase 1 (JAK1) made for the treatment of rheumatoid arthritis. A population pharmacokinetic/pharmacodynamic analysis was conducted to characterize the pharmacokinetic and pharmacodynamic profile of H018 and its active metabolite using data from 48 healthy Chinese volunteers who received a single dose of 10-160 mg of H018 in a phase I clinical study. A two-compartment model with delayed absorption and linear elimination adequately described the pharmacokinetic data of H018. The apparent clearance of H018 was estimated to be 39.0 L/h, and triglyceride was identified as a covariate on it. Pharmacokinetic data of the active metabolite could be well described by a two-compartment model with linear elimination. The exposure-effect relationships in terms of pSTAT1 inhibition were well described by a direct response model, with exposure captured by an active moiety that consisted of H018 and its metabolite, weighted by the ratio of in vitro JAK1 inhibitory activity (1.13). The estimated EC50 value for the active moiety is 601 nM. In the simulation using the final model, the inhibitory effect appeared to have reached a plateau in the high-dose groups, with max inhibition rates of 81.42 %, 88.42 %, and 91.89 % for 80, 120, and 160 mg dose groups, respectively. Taken together, this study will provide an instructive reference of dose selection for subsequent clinical trials.

Two novel pathogenic variants in the TCOF1 found in two Chinese cases of Treacher Collins syndrome.

BACKGROUND: Treacher Collins Ι syndrome (TCS1, OMIM:154500) is an autosomal dominant disease with a series of clinical manifestations such as craniofacial dysplasia including eye and ear abnormalities, small jaw deformity, cleft lip, as well as repeated respiratory tract infection and conductive hearing loss. Two cases of Treacher Collins syndrome with TCOF1(OMIM:606847) gene variations were reported in the article, with clinical characteristics, gene variants and the etiology. METHODS: The clinical data of two patients with Treacher Collins syndrome caused by TCOF1 gene variation were retrospectively analyzed. The whole exome sequencing (WES) was performed to detect the pathogenic variants of TCOF1 gene in the patients, and the verification of variants were confirmed by Sanger sequencing. RESULTS: Proband 1 presented with bilateral craniofacial deformities, conductive hearing loss and recurrent respiratory tract infection. Proband 2 showed bilateral craniofacial malformations with cleft palate, which harbored similar manifestations in her family. She died soon after birth due to dyspnea and feeding difficulties. WES identified two novel pathogenic variants of TCOF1 gene in two probands, each with one variant. According to the American College of Medical Genetics and Genomics, the heterozygous variation NM_001371623.1: c.877del (p. Ala293Profs*34) of TCOF1 gene was detected in Proband 1, which was evaluated as a likely pathogenic (LP) and de novo variant. Another variant found in Proband 2 was NM_001135243.1: c.1660_1661del (p. D554Qfs*3) heterozygous variation, which was evaluated as a pathogenic variation and the variant inherited from the mother. To date, the two variants have not been reported before. CONCLUSION: Our study found two novel pathogenic variants of TCOF1 gene and clarified the etiology of Treacher Collins syndrome. We also enriched the phenotypic spectrum of Treacher Collins syndrome and TCOF1 gene variation spectrum in the Chinese population, and provided the basis for clinical diagnosis, treatment and genetic counseling.

A microbial knowledge graph-based deep learning model for predicting candidate microbes for target hosts.

Predicting interactions between microbes and hosts plays critical roles in microbiome population genetics and microbial ecology and evolution. How to systematically characterize the sophisticated mechanisms and signal interplay between microbes and hosts is a significant challenge for global health risks. Identifying microbe-host interactions (MHIs) can not only provide helpful insights into their fundamental regulatory mechanisms, but also facilitate the development of targeted therapies for microbial infections. In recent years, computational methods have become an appealing alternative due to the high risk and cost of wet-lab experiments. Therefore, in this study, we utilized rich microbial metagenomic information to construct a novel heterogeneous microbial network (HMN)-based model named KGVHI to predict candidate microbes for target hosts. Specifically, KGVHI first built a HMN by integrating human proteins, viruses and pathogenic bacteria with their biological attributes. Then KGVHI adopted a knowledge graph embedding strategy to capture the global topological structure information of the whole network. A natural language processing algorithm is used to extract the local biological attribute information from the nodes in HMN. Finally, we combined the local and global information and fed it into a blended deep neural network (DNN) for training and prediction. Compared to state-of-the-art methods, the comprehensive experimental results show that our model can obtain excellent results on the corresponding three MHI datasets. Furthermore, we also conducted two pathogenic bacteria case studies to further indicate that KGVHI has excellent predictive capabilities for potential MHI pairs.

Effects of polyethylene microplastics occurrence on estrogens degradation in soil.

Growing focus has been drawn to the continuous detection of high estrogens levels in the soil environment. Additionally, microplastics (MPs) are also of growing concern worldwide, which may affect the environmental behavior of estrogens. However, little is known about effects of MPs occurrence on estrogens degradation in soil. In this study, polyethylene microplastics (PE-MPs) were chosen to examine the influence on six common estrogens (estrone (E1), 17α-estradiol (17α-E2), 17ß-estradiol (17ß-E2), estriol (E3), diethylstilbestrol (DES), and 17α-ethinylestradiol (17α-EE2)) degradation. The results indicated that PE-MPs had little effect on the degradation of E3 and DES, and slightly affected the degradation of 17α-E2, however, significantly inhibited the degradation of E1, 17α-EE2, and 17ß-E2. It was explained that (i) obvious oxidation reaction occurred on the surface of PE-MPs, indicating that PE-MPs might compete with estrogens for oxidation sites, such as redox and biological oxidation; (ii) PE-MPs significantly changed the bacterial community in soil, resulting in a decline in the abundance of some bacterial communities that biodegraded estrogens. Moreover, the rough surface of PE-MPs facilitated the estrogen-degrading bacterial species (especially for E1, E2, and EE2) to adhere, which decreased their reaction to estrogens. These findings are expected to deepen the understanding of the environmental behavior of typical estrogens in the coexisting system of MPs.

SERS detection of volatile gas in spoiled pork with the Ag/MoS2 nano-flower cavity/PVDF micron-bowl cavity (FIB) substrate.

Putrescine and cadaverine are significant volatile indicators used to assess the degree of food spoilage. Herein, we propose a micro-nano multi cavity structure for surface-enhanced Raman spectroscopy (SERS) to analyze the volatile gas putrescine and cadaverine in decomposing food. The MoS2 nano-flowers are inserted into a PVDF micro-cavity through in-situ growth, followed by vacuum evaporation technology of Ag nanoparticles to form an Ag/MoS2 nano-flower cavity/PVDF micron-bowl cavity (FIB) substrate. The micro-nano multi cavity structure can improve the capture capacity of both light and gas, thereby exhibiting high sensitivity (EF = 7.71 × 107) and excellent capability for gas detection of 2-naphthalenethiol. The SERS detections of the putrescine and cadaverine are achieved in the spoiled pork samples with the FIB substrate. Therefore, this substrate can provide an efficient, accurate, and feasible method for the specific and quantitative detection in the food safety field.

Cost-effectiveness analysis of Shexiang Baoxin Pill (MUSKARDIA) as the add-on treatment to standard therapy for stable coronary artery disease in China.

BACKGROUND: Recent evidence indicates that Shexiang Baoxin Pill (MUSKARDIA), as an add-on treatment to standard therapy for stable coronary artery disease (CAD), is effective. Nevertheless, the cost-effectiveness of introducing the Shexiang Baoxin Pill (Abbreviation SBP) to the current standard treatment for patients with CAD in China remains unknown. OBJECTIVE: The objective of this study was to assess the cost-effectiveness of introducing SBP into the current standard treatment in China for patients with CAD. METHOD: The effects of two treatment strategies-the SBP group (SBP combined with standard therapy) and the standard therapy group (placebo combined with standard therapy)-were simulated using a long-term Markov model. The simulation subjects might experience non-fatal MI and/or stroke or vascular or non-vascular death events. The study parameters were primarily derived from the MUSKARDIA trial, which was a multicenter, double-blind, placebo-controlled phase IV randomized clinical trial. Furthermore, age-related change, event costs, and event utilities were drawn from publicly available sources. Both costs and health outcomes were discounted at 5.0% per annum. One-way and probabilistic sensitivity analyses were conducted to verify the robustness of the model. Based on the MUSKARDIA trial results, the risk with the events of major adverse cardiovascular events (MACE) was decreased (P < 0.05) in the female subgroup treated with SBP therapy compared with standard therapy. Consequently, a scenario analysis based on subgroups of Chinese females was conducted for this study. Incremental cost-effectiveness ratios (ICERs) were assessed for each strategy for costs per quality-adjusted life-year (QALY) saved. RESULTS: After 30 years of simulation, the SBP group has added 0.32 QALYs, and the cost has been saved 841.00 CNY. Compared with the standard therapy, the ICER for the SBP therapy was -2628.13 CNY per QALY. Scenario analyses of Chinese females showed that, after 30 years of simulation, the SBP therapy has been increased by 0.82 QALYs, and the cost has been reduced by 19474.00 CNY. Compared with the standard therapy, the ICER for the SBP therapy was -26569.51 CNY per QALY. Similar results were obtained in various extensive sensitivity analyses. CONCLUSIONS: This is the first study to evaluate the cost-effectiveness of SBP in the treatment of CAD. In conclusion, SBP as an add-on treatment to standard therapy appears to be a cost-effective strategy for CAD in Chinese patients.

A programmed cell death-related gene signature to predict prognosis and therapeutic responses in liver hepatocellular carcinoma.

BACKGROUND: Programmed cell death (PCD) functions critically in cancers and PCD-related genes are associated with tumor microenvironment (TME), prognosis and therapeutic responses of cancer patients. This study stratified hepatocellular carcinoma (HCC) patients and develop a prognostic model for predicting prognosis and therapeutic responses. METHODS: Consensus clustering analysis was performed to subtype HCC patients in The Cancer Genome Atlas (TCGA) database. Differentially expressed genes (DEGs) among the subtypes were filtered and subjected to the least absolute shrinkage and selection operator (LASSO) regression analysis and univariate Cox regression analysis to filter prognostic genes. A PCD-related prognostic gene signature in TCGA was constructed and validated in ICGC-LIRI-JP and GSE14520 datasets. TME was analyzed using CIBERSORT, MCP-counter, TIMER and EPIC algorithms. Drug sensitivity was predicted by oncoPredict package. Spearman analysis was used to detect correlation. RESULTS: Four molecular subtypes were categorized based on PCD-related genes. Subtype C1 showed the poorest prognosis, the most infiltration of Fibroblasts, dentritic cell (DC) and cancer-associated fibroblasts (CAFs), and the highest TIDE score. C4 had a better prognosis survival outcome, and lowest immune cell infiltration. The survival outcomes of C2 and C3 were intermediate. Next, a total of 69 co-DEGs were screened among the four subtypes and subsequently we identified five prognostic genes (MCM2, SPP1, S100A9, MSC and EPO) for developing the prognostic model. High-risk patients not only had unfavorable prognosis, higher clinical stage and grade, and more inflammatory pathway enrichment, but also possessed higher possibility of immune escape and were more sensitive to Cisplatin and 5. Fluorouracil. The robustness of the prognostic model was validated in external datasets. CONCLUSION: This study provides new insights into clinical subtyping and the PCD-related prognostic signature may serve as a useful tool to predict prognosis and guide treatments for patients with HCC.