Search

Background: This study aimed to investigate the knowledge, attitudes, and practices (KAP) toward cardiovascular complications among end-stage renal disease patients undergoing maintenance hemodialysis. Methods: This web-based cross-sectional study was conducted at Guangdong Provincial People's Hospital between December 2022, and May 2023. Results: A total of 545 valid questionnaires were collected, with an average age of 57.72 ± 13.47 years. The mean knowledge, attitudes and practices scores were 8.17 ± 2.9 (possible range: 0–24), 37.63 ± 3.80 (possible range: 10–50), 33.07 ± 6.10 (possible range: 10–50) respectively. Multivariate logistic regression analysis showed that patients from non-urban area had lower knowledge compared to those from urban area (odds ratio (OR) = 0.411, 95% CI: 0.262–0.644, P < 0.001). Furthermore, higher levels of education were associated with better knowledge, as indicated by OR for college and above (OR = 4.858, 95% CI: 2.483–9.504), high school/vocational school (OR = 3.457, 95% CI: 1.930–6.192), junior high school (OR = 3.300, 95% CI: 1.945–5.598), with primary school and below as reference group (all P < 0.001). Besides, better knowledge (OR = 1.220, 95% CI: 1.132–1.316, P < 0.001) and higher educational levels were independently associated with positive attitudes. Specifically, individuals with a college degree and above (OR = 2.986, 95% CI: 1.411–6.321, P = 0.004) and those with high school/vocational school education (OR = 2.418, 95% CI: 1.314–4.451, P = 0.005) have more positive attitude, with primary school and below as reference group. Next, better attitude (OR = 1.174, 95% CI: 1.107–1.246, P < 0.001) and higher education were independently associated with proactive practices. Those with college and above (OR = 2.870, 95% CI: 1.359–6.059, P = 0.006), and those with high school/vocational school education (OR = 1.886, 95% CI: 1.032–3.447, P = 0.039) had more proactive practices, with primary school and below as reference group. Conclusions: End-stage renal disease patients undergoing maintenance hemodialysis demonstrated insufficient knowledge, positive attitudes, and moderate practices regarding cardiovascular complications. Targeted interventions should prioritize improving knowledge and attitudes, particularly among patients with lower educational levels and income, to enhance the management of cardiovascular complications in end-stage renal disease. [ABSTRACT FROM AUTHOR]

Background: Hepatocellular carcinoma (HCC) ranks as the third most common cause of cancer related death globally, representing a substantial challenge to global healthcare systems. In China, the primary risk factor for HCC is the hepatitis B virus (HBV). Aberrant serum glycoconjugate levels have long been linked to the progression of HBV-associated HCC (HBV-HCC). Nevertheless, few study systematically explored the dysregulation of glycoconjugates in the progression of HBV-associated HCC and their potency as the diagnostic and prognostic biomarker. Methods: An integrated strategy that combined transcriptomics, glycomics, and glycoproteomics was employed to comprehensively investigate the dynamic alterations in glyco-genes, N-glycans, and glycoproteins in the progression of HBV- HCC. Results: Bioinformatic analysis of Gene Expression Omnibus (GEO) datasets uncovered dysregulation of fucosyltransferases (FUTs) in liver tissues from HCC patients compared to adjacent tissues. Glycomic analysis indicated an elevated level of fucosylated N-glycans, especially a progressive increase in fucosylation levels on IgA1 and IgG2 determined by glycoproteomic analysis. Conclusions: The findings indicate that the abnormal fucosylation plays a pivotal role in the progression of HBV-HCC. Systematic and integrative multi-omic analysis is anticipated to facilitate the discovery of aberrant glycoconjugates in tumor progression. [ABSTRACT FROM AUTHOR]

Renal inflammation is a pivotal mechanism underlying the pathophysiology of diabetic nephropathy (DN). The Src homology phosphatase 2 (SHP2) has been demonstrated to be linked to diabetes-induced inflammation, yet its roles and explicit molecular mechanisms in DN remain unexplored. Here, we report that SHP2 activity is upregulated in both DN patients and db/db mice. In addition, pharmacological inhibition of SHP2 with its specific inhibitor PHPS1 alleviates DN in db/db mice and attenuates renal inflammation. In vitro, PHPS1 administration prevents inflammatory responses in HK-2 cells stimulated by high glucose (HG). Mechanistically, PHPS1 represses HG-induced activation of the proinflammatory ERK/NF-κB signaling pathway, and these inhibitory effects are blocked in the presence of an ERK specific inhibitor, hence demonstrating that PHPS1 suppresses ERK/NF-κB pathway-mediated inflammation. Moreover, PHPS1 retards ERK/NF-κB pathway activation in db/db mice, and histologically, SHP2 activity is positively correlated with ERK/NF-κB activation in DN patients. Taken together, these findings identify SHP2 as a potential therapeutic target and show that its pharmacological inhibition might be a promising strategy to mitigate DN. -rV21qwpHSeiT1S94nwGvk Video Abstract [ABSTRACT FROM AUTHOR]

Background: Inflammatory bowel disease (IBD), including Crohn's disease (CD) and ulcerative colitis (UC), is increasing worldwide. Although there is currently no completely curative treatment, helminthic therapy shows certain therapeutic potential for UC. Many studies have found that Trichinella spiralis (T.s) has a protective effect on UC, but the specific mechanism is still unclear. Methods: Balb/c mice drank dextran sulfate sodium (DSS) to induce acute colitis and then were treated with T.s. In vitro experiments, the LPS combination with ATP was used to induce the pyroptosis model, followed by intervention with crude protein from T.s (T.s cp). Additionally, the pyroptosis agonist of NSC or the pyroptosis inhibitor vx-765 was added to intervene to explore the role of pyroptosis in DSS-induced acute colitis. The degree of pyroptosis was evaluated by western blot, qPCR and IHC, etc., in vivo and in vitro. Results: T.s intervention significantly inhibited NLRP3 inflammasome activation and GSDMD-mediated pyroptosis by downregulating the expression of pyroptosis-related signatures in vitro (cellular inflammatory model) and in vivo (DSS-induced UC mice model). Furthermore, blockade of GSDMD-mediated pyroptosis by the caspase-1 inhibitor vx-765 has a similar therapeutic effect on DSS-induced UC mice with T.s intervention, thus indicating that T.s intervention alleviated DSS-induced UC in mice by inhibiting GSDMD-mediated pyroptosis. Conclusion: This study showed that T.s could alleviate the pathological severity UC via GSDMD-mediated pyroptosis, and it provides new insight into the mechanistic study and application of helminths in treating colitis. [ABSTRACT FROM AUTHOR]

Fusarium head blight (FHB) caused by Fusarium species, seriously threatens the safety of wheat (Triticum aestivum) production. Resistant cultivars and fungicides are frequently used to control these FHB pathogens. However, Fusarium species have been adapting the current FHB control approaches in a manner that raises concern for future FHB control strategies, which could lead to a greater risk of FHB outbreaks. In this study, a total of 521 strains of Fusarium were isolated from Sichuan province of China, to investigate the diversity of Fusarium species and the genes associated with their adaptation. Seven species were identified based on molecular markers and morphological analysis. The virulence assays showed that Fusarium asiaticum (Fa) and Fusarium graminearum (Fg) were the two major causal agents of FHB, with high virulence and more frequent isolates. Fungicide resistance analysis showed that four isolates had developed the resistance to carbendazim, and four isolates had developed the resistance to tebuconazole. Of note, two point-mutation variants (F200Y and E198Q) occurred in the β2-tubulin gene, leading to the carbendazim resistance. The landscape of genomic diversity was analyzed through whole-genome sequencing, revealing a total of 182,811 and 430,733 variants (including: single nucleotide polymorphisms, SNP, insertion and deletion, Indel, and structure variation, SV) among the Fa and Fg isolates, respectively. In addition, potential alterations in gene function (15.22%) were predicted among Fg variants. These alterations offer potential helps for the Fusarium species to adapt to various managements of FHB, which may increase risks in developing fungicide-resistant isolates. However, these annotated genetic variants are valuable resources for further genetic and genomic studies, as well as potential markers to assist disease risk assessment. [ABSTRACT FROM AUTHOR]

Objective: To predict the very early recurrence (VER) of patients with intrahepatic cholangiocarcinoma (ICC) based on TLSs and MVI status, and further perform prognosis stratifications. Methods: A total of 160, 51 ICC patients from two institutions between May 2012 and July 2022 were retrospectively included as training, external validation cohort. Clinical, radiological and pathological variables were evaluated and collected. Univariate and multivariate analysis were applied to select the significant factors related to VER of ICC. The factors selected were combined to perform stratification of overall survival (OS) using the Kaplan-Meier method with the log-rank test. Results: Overall, 39 patients (24.4%) had VER, whereas 121 (75.6%) did not (non-VER group). In the training cohort, the median OS was 40.5 months (95% CIs: 33.2–47.7 months). The VER group showed significantly worse OS than the non-VER group (median OS: 14.8, 95% CI:11.6–18.0 months vs. 53.4, 34.3–72.6 months; p<0.001), and it was confirmed in the validation cohort (median OS: 22.1, 95% CI: 8.8–35.4 months vs. 40.1, 21.2–59.0 months; p = 0.003). According to the univariate analysis, four variables were significantly different between the VER group and non-VER group (TLSs status, p = 0.028; differentiation, p = 0.023; MVI status, p = 0.012; diameter, p = 0.028). According to the multivariate analysis, MVI-positive status was independently associated with a higher probability of VER (odds ratio [OR], 2.5; 95% CIs,1.16–5.18; p = 0.018), whereas intra-tumoral TLSs-positive status was associated with lower odds of VER (OR, 0.43; 95% CIs, 0.19–0.97; p = 0.041). Based on the TLSs and MVI status, patients of ICC were categorized into four groups: TLSs-positive and MVI-negative (TP/MN); TLSs-negative and MVI-negative (TN/MN); TLSs-positive and MVI-positive (TP/MP), TLSs-negative and MVI-positive groups (TN/MP). In the training cohort, the four groups could be correlated with OS significantly (p<0.001), and it was confirmed in the validation cohort (p<0.001). Conclusion: Intra-tumoral TLSs and MVI status are independent predictive factors of VER after surgery, based on which immunovascular stratifications are constructed and associated with OS significantly of resectable intrahepatic cholangiocarcinoma. [ABSTRACT FROM AUTHOR]

Background: Inflammatory bowel disease (IBD), including Crohn's disease (CD) and ulcerative colitis (UC), is increasing worldwide. Although there is currently no completely curative treatment, helminthic therapy shows certain therapeutic potential for UC. Many studies have found that Trichinella spiralis (T.s) has a protective effect on UC, but the specific mechanism is still unclear. Methods: Balb/c mice drank dextran sulfate sodium (DSS) to induce acute colitis and then were treated with T.s. In vitro experiments, the LPS combination with ATP was used to induce the pyroptosis model, followed by intervention with crude protein from T.s (T.s cp). Additionally, the pyroptosis agonist of NSC or the pyroptosis inhibitor vx-765 was added to intervene to explore the role of pyroptosis in DSS-induced acute colitis. The degree of pyroptosis was evaluated by western blot, qPCR and IHC, etc., in vivo and in vitro. Results: T.s intervention significantly inhibited NLRP3 inflammasome activation and GSDMD-mediated pyroptosis by downregulating the expression of pyroptosis-related signatures in vitro (cellular inflammatory model) and in vivo (DSS-induced UC mice model). Furthermore, blockade of GSDMD-mediated pyroptosis by the caspase-1 inhibitor vx-765 has a similar therapeutic effect on DSS-induced UC mice with T.s intervention, thus indicating that T.s intervention alleviated DSS-induced UC in mice by inhibiting GSDMD-mediated pyroptosis. Conclusion: This study showed that T.s could alleviate the pathological severity UC via GSDMD-mediated pyroptosis, and it provides new insight into the mechanistic study and application of helminths in treating colitis. [ABSTRACT FROM AUTHOR]

Background: Primary pulmonary hyalinizing clear cell carcinoma (HCCC) is a low-grade salivary gland-type carcinoma. Until now, 23 cases of pulmonary HCCC have been reported. Case presentation: Here, we present a patient with primary pulmonary HCCC along with vocal-cord squamous cell carcinoma (SCC) revealed by biopsy examination. The patient underwent radiotherapy for vocal-cord SCC, followed by right upper lobectomy and lymph node dissection 10 months later. Histology revealed polygonal cells with eosinophilic or clear cytoplasm in the myxoid matrix together with hyaline degeneration. The tumor involved the whole layer of the segmental bronchus and regionally involved the alveolar tissue along with one intrapulmonary lymph node. Targeted RNA sequencing revealed Ewing Sarcoma Breakpoint Region 1 (EWSR1)- activating transcription factor 1 (ATF1) fusion. We analyzed the data on pulmonary malignant tumors between 2000 and 2019 in the Surveillance, Epidemiology, and End Results (SEER) database and reviewed all cases of pulmonary HCCC with EWSR1 fusion by searching PubMed. The results showed that head and neck (HN) adenoid cystic carcinoma (ACC) (47.89%) and HNSCC (22.54%) were the most common carcinomas occurring with pulmonary salivary gland-type malignant tumors. Screening of 24 cases of pulmonary HCCC with EWSR1 fusion revealed that five cases demonstrated lymph node metastases and only two had documented tumor recurrences. HCCC is rare and easily misdiagnosed as SCC, but the treatment regimen differs between pulmonary HCCC and SCC. Conclusions: Hence, pulmonary tumors with clear cells must be diagnosed with caution. Next-generation sequencing (NGS) may be useful for diagnosis, especially in cases with a history of squamous cell carcinoma (SCC). [ABSTRACT FROM AUTHOR]

Background: A one-off sensory wellbeing workshop has been developed to help patients with eating disorders (ED) manage sensory sensitivities. The aim of this study was to evaluate and compare the outcomes of the workshop in online versus face-to-face (F2F) formats among a sample of patients with ED. Methods: Cumulative link models were applied to the outcome measures (awareness of sensory wellbeing, awareness of strategies to enhance sensory wellbeing, and confidence in managing sensory wellbeing) to test the differences between online and F2F workshops. Participants' ratings of usefulness of the workshop were also compared between online and F2F workshops. Results: A total of 14 workshops (4 online and 10 F2F) were run from 2020 to 2023. All participants reported significant and substantial improvements in all outcome measures. There was no significant difference in outcomes between online and F2F workshops. The majority of patients rated the workshops as useful. Conclusions: Both online and face-to-face formats of the sensory workshop led to improvement in sensory wellbeing management for patients with ED. Future studies are warranted to test the impact of the workshop on ED treatment outcomes. Plain English summary: People with eating disorders often have sensory issues, which can include being too sensitive to some senses (hearing, smell or taste, for example) or not sensitive enough. Explaining how the sensory system works and developing helpful strategies to manage sensory difficulties could be beneficial in the process of therapy. To try and support this, clinicians and researchers designed a sensory wellbeing workshop to help people become more aware of their sensory wellbeing and teach them strategies to manage their sensory wellbeing. The workshop can be delivered online or face-to-face. This study examined the feedback for online and face-to-face workshops. We found that both formats were helpful for people with eating disorders. We also discuss possible ways to develop and test the workshop further in order to better support patients with sensory difficulties. [ABSTRACT FROM AUTHOR]

Background: With the advent of metagenomic next-generation sequencing (mNGS), the time of DNA metabolism can be explored after bacteria be killed. In this study, we applied mNGS in investigation of the clearance profile of circulating bacteria DNA. Methods: All of the rabbits were injected with the inactivated Escherichia coli. Using mNGS, we analyzed serial samples of plasma collected from rabbits to detect clearance profile of circulating E. coli DNA. Results: In this study, we found that the of E. coli DNA could still be detected 6 h after injecting killed bacteria. The clearance half-lives associated with the 2 phases are 0.37 and 1.81 h. We also explored there is no correlation between the disease severity with the E. coli DNA reads in circulation. Conclusions: After the bacteria were completely killed, their DNA could still be detected in the blood circulation. The metabolism of bacterial DNA in the circulation had two phases: fast and slow phases, and there were no correlations between the level of bacteria reads with the severity of patients’ disease after the bacteria have been completely killed. [ABSTRACT FROM AUTHOR]

Background: Tillage measures have been effectively adopted for mitigating waterlogging damage in field crops, yet little is known about the role of tillage measures in crop responses to waterlogging. A field experiment was performed to investigate the effect of conventional planting (CK), small ridge planting (SR), big ridge planting (BR) and film side planting (FS) on soil available nutrients and enzymatic activity, chlorophyll contents, leaf nutrients, soluble protein, soluble sugar, nitrate reductase, antioxidant enzyme activity, lipid peroxidation, agronomic traits and yield of rapeseed under waterlogging stress conditions. Results: Tillage measures remarkably improved rapeseed growth and yield parameters under waterlogging stress conditions. Under waterlogging conditions, rapeseed yield was significantly increased by 33.09 and 22.70% in the SR and BR groups, respectively, compared with CK. Correlation analysis showed that NO3−-N, NH4+-N, and urease in soils and malonaldehyde (MDA), superoxide dismutase (SOD), and nitrate reductase in roots were the key factors affecting rapeseed yield. The SR and BR groups had significantly increased NO3−-N by 180.30 and 139.77%, NH4+-N by 115.78 and 66.59%, urease by 41.27 and 26.45%, SOD by 6.64 and 4.66%, nitrate reductase by 71.67 and 26.67%, and significantly decreased MDA content by 14.81 and 13.35% under waterlogging stress, respectively, compared with CK. In addition, chlorophyll and N content in leaves, soluble sugar and POD in roots, and most agronomic traits were also significantly enhanced in response to SR and BR under waterlogging conditions. Conclusion: Overall, SR and BR mitigated the waterlogging damage in rapeseed mainly by reducing the loss of soil available nitrogen, decreasing the MDA content in roots, and promoting urease in soils and SOD and nitrate reductase in roots. Finally, thorough assessment of rapeseed parameters indicated that SR treatment was most effective followed by BR treatment, to alleviate the adverse effects of waterlogging stress. [ABSTRACT FROM AUTHOR]

Background: Non-communicable diseases (NCDs) are rapidly increasing in sub-Saharan African countries, where 96% of global malaria deaths occur. This study aimed to investigate the disease burden of NCDs in countries with the current highest malaria mortality.Methods: Data for this study were obtained from the Global Burden of Disease 2019 study (1990-2019). We selected the ten countries with malaria's highest age-standardised mortality rate (ASMR) and identified and ranked the five NCDs with the highest ASMR in each country. Measures of the NCDs disease burden included ASMR, age-standardised disability-adjusted life-years (DALY), years of life lost (YLL) and years lost due to a disability (YLD). The Estimated annual percentage change (EAPC) was used to examine the trends of the NCDs disease burden from 1990 to 2019.Results: As of 2019, the ASMR of chronic liver disease, kidney disease, diabetes mellitus, Alzheimer's disease and other dementias, hypertensive heart disease and stroke were higher than the global average. From 1990 to 2019, the ASMR for Alzheimer's disease and other dementias, type II diabetes mellitus, and chronic kidney disease increased by 3.0%, 10.8%, 13.3%, and the age-standardised DALY rate increased by 3.7%, 27.6%, 6.3%, and the increases tended to be in younger populations.Conclusion: The double burden of non-communicable and communicable diseases is crippling the health systems of many sub-Saharan African countries and is often neglected. The prevention, surveillance, and control of diseases require an integrated strategy, with governments and non-government organisations aligned and supported by the global initiative. [ABSTRACT FROM AUTHOR]

Background: Sporadic gastric foveolar-type adenomas are extremely rare and are usually small, flat or slightly raised lesions that occur in the oxyntic mucosa.Case Presentation: We reported here a case of a 70-year-old female with a sporadic gastric foveolar-type adenoma occurring in the mucosa at the junction of the gastric body/antrum. The adenoma was a protruding lesion of 2 × 1.8 cm sized, causing symptoms of upper gastrointestinal bleeding, and the basal and surrounding mucosa showed pseudopyloric gland metaplasia without atrophy, intestinal metaplasia, H. pylori infection, or active inflammation. It had somatic mutations in both APC and KRAS genes.Conclusions: This is the first reported case of a large sporadic gastric foveolar-type adenoma that occurred in the mucosa of pseudopyloric gland metaplasia and with Gastritis Cystica Profunda, which modify our understanding of the morphological features and molecular underpinnings of this type of lesion. [ABSTRACT FROM AUTHOR]

Background: Epizootic haemorrhagic disease virus (EHDV) and the Palyam serogroup viruses (PALV) have led to significant economic losses associated with livestock production globally. A rapid, sensitive and specific method for the detection of EHDV and PALV is critical for virus detection, monitoring, and successful control and elimination of related diseases. Results: In the present study, a recombinase polymerase amplification combined with lateral flow dipstick (RPA-LFD) assay for the co-detection of genome segment 1 (Seg-1) of EHDV and PALV was developed and evaluated. The analytical sensitivities of the established RPA-LFD assay in the detection of EHDV and PALV were 7.1 copies/µL and 6.8 copies/µL, respectively. No cross-reaction with other members of the genus Orbivirus, including African horse sickness virus, bluetongue virus, Guangxi orbivirus, Tibet orbivirus and Yunnan orbivirus was observed. The established RPA-LFD assay accurately detected 39 EHDV strains belonging to 5 serotypes and 29 PALV strains belonging to 3 serotypes. The trace back results of quantitative real-time polymerase chain reaction (qRT-PCR) and the established RPA-LFD assay on sentinel cattle were consistent. The coincidence rates of qRT-PCR and the established RPA-LFD assay in 56 blood samples from which EHDV or PALV had been isolated and 96 blood samples collected from cattle farms were more than 94.8 %. The results demonstrated that the established RPR-LFD assay is specific, sensitive and reliable, and could be applied in early clinical diagnosis of EHDV and PALV. Conclusions: This study highlights the development and application of the RPA-LFD assay in the co-detection of EHDV and PALV for the first time. The assay could be used as a potential optional rapid, reliable, sensitive and low-cost method for field diagnosis of EHDV and PALV. [ABSTRACT FROM AUTHOR]

Background: Tuberculosis (TB) remains a pressing public health issue, posing a significant threat to individuals' well-being and lives. This study delves into the TB incidence in Chinese mainland during 2014–2021, aiming to gain deeper insights into their epidemiological characteristics and explore macro-level factors to enhance control and prevention. Methods: TB incidence data in Chinese mainland from 2014 to 2021 were sourced from the National Notifiable Disease Reporting System (NNDRS). A two-stage distributed lag nonlinear model (DLNM) was constructed to evaluate the lag and non-linearity of daily average temperature (℃, Atemp), average relative humidity (%, ARH), average wind speed (m/s, AWS), sunshine duration (h, SD) and precipitation (mm, PRE) on the TB incidence. A spatial panel data model was used to assess the impact of demographic, medical and health resource, and economic factors on TB incidence. Results: A total of 6,587,439 TB cases were reported in Chinese mainland during 2014–2021, with an average annual incidence rate of 59.17/100,000. The TB incidence decreased from 67.05/100,000 in 2014 to 46.40/100,000 in 2021, notably declining from 2018 to 2021 (APC = -8.87%, 95% CI: -11.97, -6.85%). TB incidence rates were higher among males, farmers, and individuals aged 65 years and older. Spatiotemporal analysis revealed a significant cluster in Xinjiang, Qinghai, and Xizang from March 2017 to June 2019 (RR = 3.94, P < 0.001). From 2014 to 2021, the proportion of etiologically confirmed cases increased from 31.31% to 56.98%, and the time interval from TB onset to diagnosis shortened from 26 days (IQR: 10–56 days) to 19 days (IQR: 7–44 days). Specific meteorological conditions, including low temperature (< 16.69℃), high relative humidity (> 71.73%), low sunshine duration (< 6.18 h) increased the risk of TB incidence, while extreme low wind speed (< 2.79 m/s) decreased the risk. The spatial Durbin model showed positive associations between TB incidence rates and sex ratio (β = 1.98), number of beds in medical and health institutions per 10,000 population (β = 0.90), and total health expenses (β = 0.55). There were negative associations between TB incidence rates and population (β = -1.14), population density (β = -0.19), urbanization rate (β = -0.62), number of medical and health institutions (β = -0.23), and number of health technicians per 10,000 population (β = -0.70). Conclusions: Significant progress has been made in TB control and prevention in China, but challenges persist among some populations and areas. Varied relationships were observed between TB incidence and factors from meteorological, demographic, medical and health resource, and economic aspects. These findings underscore the importance of ongoing efforts to strengthen TB control and implement digital/intelligent surveillance for early risk detection and comprehensive interventions. [ABSTRACT FROM AUTHOR]

Objective: Duchenne muscular dystrophy (DMD) is a devastating X-linked neuromuscular disorder caused by various defects in the dystrophin gene and still no universal therapy. This study aims to identify the hub genes unrelated to excessive immune response but responsible for DMD progression and explore therapeutic siRNAs, thereby providing a novel treatment. Methods: Top ten hub genes for DMD were identified from GSE38417 dataset by using GEO2R and PPI networks based on Cytoscape analysis. The hub genes unrelated to excessive immune response were identified by GeneCards, and their expression was further verified in mdx and C57 mice at 2 and 4 months (M) by (RT-q) PCR and western blotting. Therapeutic siRNAs were deemed as those that could normalize the expression of the validated hub genes in transfected C2C12 cells. Results: 855 up-regulated and 324 down-regulated DEGs were screened from GSE38417 dataset. Five of the top 10 hub genes were considered as the candidate genes unrelated to excessive immune response, and three of these candidates were consistently and significantly up-regulated in mdx mice at 2 M and 4 M when compared with age-matched C57 mice, including Col1a2, Fbn1 and Fn1. Furthermore, the three validated up-regulated candidate genes can be significantly down-regulated by three rational designed siRNA (p < 0.0001), respectively. Conclusion: COL1A2, FBN1 and FN1 may be novel biomarkers for DMD, and the siRNAs designed in our study were help to develop adjunctive therapy for Duchenne muscular dystrophy. [ABSTRACT FROM AUTHOR]

Background: The new coronavirus pneumonia (NCP) caused by COVID-19 has affected more than 46 million people worldwide. In China, primary care has played a vital role during the COVID-19 outbreak, and it is important to examine the challenges faced by general practitioners (GPs). This study investigated the roles, preparedness and training needs of GPs in China in managing the NCP outbreak. Based on the outcomes of the study, we hope to take lessons and identify how GPs could be supported in delivering their gatekeeping roles and clinical duties in times of infectious disease outbreak. Methods: An online survey on the official website of Shenzhen Continuing Education Center. It included questions on GPs' demographics, their awareness of COVID-19 and their preparedness in managing suspected cases of NCP, as well as referrals and their training needs. Conditional multi-variate logistic models were used to investigate the relationships between GPs' preparedness, situational confidence and anxiety. Results: GPs' clinical practice was significantly affected. GPs endeavoured to answer a flood of COVID-19-related enquiries, while undertaking community preventive tasks. In addition to in-person consultations, GP promoted COVID-19 awareness and education through telephone consultations, physical posters and social media. Overall GPs in Shenzhen felt well supported with adequate Personal Protective Equipment (PPE) and resources from secondary care services. Higher levels of self-perceived preparedness (OR = 2.19; 95%CI, 1.04–4.61), lower level of anxiety (OR = 0.56; 95%CI, 0.29–1.09) and fewer perceived family worries (OR = 0.37; 95%CI, 0.12–1.12) were associated with better confidence in coping at work. Conclusions: Training and supporting GPs while reducing their (and their families') anxiety increase their confidence in delivering the important roles of gatekeeping in face of major disease outbreaks. [ABSTRACT FROM AUTHOR]

Background: The formal risk assessment is essential in the management of acute coronary syndrome (ACS). In this study, we develop a risk model for the prediction of 3-year mortality for Chinese ACS patients with machine learning algorithms.Methods: A total of 2174 consecutive patients who underwent angiography with ACS were enrolled. The missing data among baseline characteristics were imputed using the MissForest algorithm based on random forest method. In model development, a least absolute shrinkage and selection operator (LASSO) derived Cox regression with internal tenfold cross-validation was used to identify the predictors for 3-year mortality. The clinical performance was assessed with decision curve analysis.Results: The average follow-up period was 27.82 ± 13.73 months; during the 3 years of follow up, 193 patients died (mortality rate 8.88%). The Kaplan-Meier estimate of 3-year mortality was 0.91 (95% confidence interval (CI): 0.890.92). After feature selection, 6 predictors were identified: Age," "Creatinine," "Hemoglobin," "Platelets," "aspartate transaminase (AST)" and "left ventricular ejection fraction (LVEF)". At tenfold internal validation, our risk model performed well in both discrimination (area under curve (AUC) of receiver operating characteristic (ROC) analysis was 0.768) and calibration (calibration slope was approximately 0.711). As a comparison, the AUC and calibration slope were 0.701 and 0.203 in Global Registry of Acute Coronary Events (GRACE) risk score, respectively. Additionally, the highest net benefit of our model within the entire range of threshold probability for clinical intervention by decision curve analysis demonstrated the superiority of it in daily practice.Conclusion: Our study developed a prediction model for 3-year morality in Chinese ACS patients. The methods of missing data imputation and model derivation base on machine learning algorithms improved the ability of prediction. . Trial registration ChiCTR, ChiCTR-OOC-17010433. Registered 17 February 2017-Retrospectively registered. [ABSTRACT FROM AUTHOR]

Background: Epidemiological studies on the association between coffee intake and cancer risk have yielded inconsistent results. To summarize and appraise the quality of the current evidence, we conducted an umbrella review of existing findings from meta-analyses of observational studies.Methods: We searched PubMed, Embase, Web of Science and the Cochrane database to obtain systematic reviews and meta-analyses of associations between coffee intake and cancer incidence. For each association, we estimated the summary effect size using the fixed- and random-effects model, the 95% confidence interval, and the 95% prediction interval. We also assessed heterogeneity, evidence of small-study effects, and excess significance bias.Results: Twenty-eight individual meta-analyses including 36 summary associations for 26 cancer sites were retrieved for this umbrella review. A total of 17 meta-analyses were significant at P ≤ 0.05 in the random-effects model. For the highest versus lowest categories, 4 of 26 associations had a more stringent P value (P ≤ 10- 6). Associations for five cancers were significant in dose-response analyses. Most studies (69%) showed low heterogeneity (I2 ≤ 50%). Three and six associations had evidence of excessive significance bias and publication bias, respectively. Coffee intake was inversely related to the risk of liver cancer and endometrial cancer and was characterized by dose-response relationships. There were no substantial changes when we restricted analyses to meta-analysis of cohort studies.Conclusions: There is highly suggestive evidence for an inverse association between coffee intake and risk of liver and endometrial cancer. Further research is needed to provide more robust evidence for cancer at other sites. [ABSTRACT FROM AUTHOR]

Background: Residential mobility is believed to influence the occurrence and development of cancer; however, the results are inconclusive. Furthermore, limited studies have been conducted on Asian populations. This study aimed to evaluate the relationship between residential mobility and liver cancer risk among Chinese women. Methods: We enrolled 72,818 women from urban Shanghai between 1996 and 2000, and then followed them until the end of 2016. Cox regression models were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) to assess the association between residential mobility and liver cancer risk. A linear trend test was conducted by ranking variables. A sensitivity analysis was also conducted, excluding participants with follow-up times of less than 2 years, to prevent potential bias. Results: During the 1,269,765 person-years of follow-up, liver cancer was newly diagnosed in 259 patients. Domestic migration (HR = 1.47, 95% CI, 1.44–1.50), especially immigration to Shanghai (HR = 1.47, 95% CI, 1.44–1.50) was associated with an increased risk of liver cancer. In addition, migration frequency, age at initial migration and first immigration to Shanghai had linear trends with an increased liver cancer risk (Ptrend <0.001). The results were similar when excluding participants with less than two years of follow-up. Conclusions: The possible association between residential mobility and a higher risk of liver cancer in women could suggest the need for effective interventions to reduce adverse environmental exposures and enhance people's health. [ABSTRACT FROM AUTHOR]

Background: Respiratory infectious diseases (RIDs) remain a pressing public health concern, posing a significant threat to the well-being and lives of individuals. This study delves into the incidence of seven primary RIDs during the period 2017–2021, aiming to gain deeper insights into their epidemiological characteristics for the purpose of enhancing control and prevention strategies. Methods: Data pertaining to seven notifiable RIDs, namely, seasonal influenza, pulmonary tuberculosis (PTB), mumps, scarlet fever, pertussis, rubella and measles, in the mainland of China between 2017 and 2021 were obtained from the National Notifiable Disease Reporting System (NNDRS). Joinpoint regression software was utilized to analyze temporal trends, while SaTScan software with a Poisson probability model was used to assess seasonal and spatial patterns. Results: A total of 11,963,886 cases of the seven RIDs were reported during 2017–2021, and yielding a five-year average incidence rate of 170.73 per 100,000 individuals. Among these RIDs, seasonal influenza exhibited the highest average incidence rate (94.14 per 100,000), followed by PTB (55.52 per 100,000), mumps (15.16 per 100,000), scarlet fever (4.02 per 100,000), pertussis (1.10 per 100,000), rubella (0.59 per 100,000), and measles (0.21 per 100,000). Males experienced higher incidence rates across all seven RIDs. PTB incidence was notably elevated among farmers and individuals aged over 65, whereas the other RIDs primarily affected children and students under 15 years of age. The incidences of PTB and measles exhibited a declining trend from 2017 to 2021 (APC = −7.53%, P = 0.009; APC = −40.87%, P = 0.02), while the other five RIDs peaked in 2019. Concerning seasonal and spatial distribution, the seven RIDs displayed distinct characteristics, with variations observed for the same RIDs across different regions. The proportion of laboratory-confirmed cases fluctuated among the seven RIDs from 2017 to 2021, with measles and rubella exhibiting higher proportions and mumps and scarlet fever showing lower proportions. Conclusions: The incidence of PTB and measles demonstrated a decrease in the mainland of China between 2017 and 2021, while the remaining five RIDs reached a peak in 2019. Overall, RIDs continue to pose a significant public health challenge. Urgent action is required to bolster capacity-building efforts and enhance control and prevention strategies for RIDs, taking into account regional disparities and epidemiological nuances. With the rapid advancement of high-tech solutions, the development and effective implementation of a digital/intelligent RIDs control and prevention system are imperative to facilitate precise surveillance, early warnings, and swift responses. [ABSTRACT FROM AUTHOR]

Background: There is presently no effective and safe vaccine for Toxoplasma gondii for humans. The study described here was designed to search for a novel group of optimal B cell and T cell epitopes from Toxoplasma membrane proteins using genome-wide comprehensive screening. Methods: The amino acid sequences of membrane proteins of T. gondii were obtained from the UniProt database. The ABCPred and BepiPred servers were employed to predict the linear B cell epitopes. The Immune Epitope Database (IEDB) online service was utilized to forecast T cell epitopes within T. gondii membrane proteins that bind to human leukocyte antigen (HLA) class I (HLA-I) or HLA-II molecules. Results: From the 314 membrane proteins of T. gondii, a total of 14 linear B cell epitopes embedded in 12 membrane proteins were identified. Eight epitopes for major histocompatibility complex (MHC) class I (MHC-I) molecules and 18 epitopes for MHC-II molecules were ultimately selected, for which world population coverage percentiles were 71.94% and 99.76%, respectively. The top rated combinations of linear B cell epitopes and T cell epitopes covering both BALB/c mice and a majority of the human population were identified for the development of a protective vaccine. Conclusions: The ultimate vaccine construct described here, which comprises B cells, MHC-I and MHC-II epitopes, might protect individuals against T. gondii infection by inducing humoral and cellular immune responses. [ABSTRACT FROM AUTHOR]

Background: Linkage disequilibrium (LD) analysis is broadly utilized in genetics to understand the evolutionary and demographic history and helps geneticists identify genes associated with interested inherited traits, such as diseases. There are some tools for linkage disequilibrium analysis either in a local or online way; however, there has been no such tool supporting both graphical user interface (GUI) and parallel computing. Results: We developed a GUI software called LDkit for LD analysis, which supports parallel computing. The LDkit supports both variant call format (VCF) and PLINK 'ped + map' format. At the same time, users could also just analyze a subset of individuals from the whole population. The LDkit reads the data by block and then paralleled the computation process by monitoring the usage of processes. Assessment on the Human 1000 genome data showed that when paralleled with 32 threads, the running time was reduced to less than 6 minutes from ~77 minutes using the chromosome 22 dataset with 1,103,547 SNPs and 2504 individuals. Conclusions: The software LDkit can be effectively used to calculate and plot LD decay, LD block, and linkage disequilibrium analysis between a site and a given region. Most importantly, both graphical user interface (GUI) and stand-alone packages are available for users' convenience. LDkit was written in JAVA language under cross-platform support. [ABSTRACT FROM AUTHOR]

Background: Patients with spondyloarthritis (SpA)/HLA-B27-associated acute anterior uveitis (AAU) experience recurring acute flares, which pose significant visual and financial challenges. Despite established links between SpA and HLA-B27-associated AAU, the exact mechanism involved remains unclear, and further understanding is needed for effective prevention and treatment. Methods: To investigate the acute pathogenesis of SpA/HLA-B27-associated AAU, Mendelian randomization (MR) and single-cell transcriptomic analyses were employed. The MR incorporated publicly available protein quantitative trait locus data from previous studies, along with genome-wide association study data from public databases. Causal relationships between plasma proteins and anterior uveitis were assessed using two-sample MR. Additionally, colocalization analysis was performed using Bayesian colocalization. Single-cell transcriptome analysis utilized the anterior uveitis dataset from the Gene Expression Omnibus (GEO) database. Dimensionality reduction, clustering, transcription factor analysis, pseudotime analysis, and cell communication analysis were subsequently conducted to explore the underlying mechanisms involved. Results: Mendelian randomization analysis revealed that circulating levels of AIF1 and VARS were significantly associated with a reduced risk of developing SpA/HLA-B27-associated AAU, with AIF1 showing a robust correlation with anterior uveitis onset. Colocalization analysis supported these findings. Single-cell transcriptome analysis showed predominant AIF1 expression in myeloid cells, which was notably lower in the HLA-B27-positive group. Pseudotime analysis revealed dendritic cell terminal positions in differentiation branches, accompanied by gradual decreases in AIF1 expression. Based on cell communication analysis, CD141+CLEC9A+ classic dendritic cells (cDCs) and the APP pathway play crucial roles in cellular communication in the Spa/HLA-B27 group. Conclusions: AIF1 is essential for the pathogenesis of SpA/HLA-B27-associated AAU. Myeloid cell differentiation into DCs and decreased AIF1 levels are also pivotal in this process. [ABSTRACT FROM AUTHOR]

Background: Aicardi-Goutières syndrome (AGS) is a rare hereditary early-onset encephalopathy characterized by upregulation of the type I interferon pathway, poorly responsive to conventional immunosuppression. Case presentation: We describe a 7-year-old Chinese boy who developed symptoms at the age of 6 months. He presented with a chilblain-like rash, leukopenia, neutropenia, elevated liver enzymesgrowth retardation, microcephaly, elevated acute phase reactants, intracranial calcification and leukodystrophy. At the age of 3 years old, whole-exome sequencing confirmed a de novo heterozygous gain-of-function mutation, c.1016 C > A (p.Ala339Asp), in the IFIH1 gene, and he was diagnosed with AGS7. He was treated with ruxolitinib accompanied by steroids and thalidomide for about four years. The rash, hematological manifestations, and the liver function were all improved, but the erythrocyte sedimentation rate remained consistently elevated until the addition of tocilizumab, a monoclonal antibody against interleukin 6. Conclusions: Ruxolitinib was not successful in suppressing the inflammatory process, and tocilizumab produced highly encouraging results in reducing the inflammatory reaction of AGS. The study makes a significant contribution to the literature because we may found a potential alternative therapeutic option for AGS. [ABSTRACT FROM AUTHOR]

Background: NLRP3-associated autoinflammatory disease (NLRP3-AID), caused by mutations of NLRP3, is one of the autoinflammatory diseases affecting inflammasomes. Since there are little cases of Chinese NLRP3-AID, we reported 14 Chinese NLRP3-AID patients in our center and summarized the clinical features of all Chinese patients by reviewing the literature.Results: Fourteen patients had been diagnosed as NLRP3-AID in our center. 12 different NLRP3 variants were identified, among which one is novel: p.Leu361Trp. Rash, recurrent fever, arthritis/arthralgia, uveitis, sensorineural deafness, symptoms of central neural systems (CNS), and increased inflammatory markers (including CRP, ESR, except Ferritin) were the common findings in Chinese patients. The frequencies of fever, neurological symptoms, musculoskeletal manifestations and ocular manifestations in Chinese patients might differ from that of patients from other regions. Besides, we also found clubbing fingers and optic neuritis in some NLRP3-AID patients, which were not commonly mentioned in previous reports.Conclusion: In our study, we expanded the clinical spectrum as well as the genetic pathogenic variants of NLRP3-AID. We also found that there were some differences between Chinese patients and patients from other regions, and that Chinese patients were more likely to develop severe symptoms. [ABSTRACT FROM AUTHOR]

Background: Both gastric adenocarcinoma with primitive enterocyte phenotype (GAPEP) (including hepatoid adenocarcinoma) and alpha-fetoprotein (AFP)-producing gastric adenocarcinoma have poor prognoses. However, the value of the serum AFP test and AFP/glypican-3 (GPC3)/spalt-like transcription factor 4 (SALL4) immunohistochemistry is still not clear, and these two methods have not yet been thoroughly compared.Methods: We collected 421 consecutive non-neoadjuvant surgically or endoscopically resected gastric adenocarcinoma patients with serum AFP results before surgery (group A). We divided these cases into serum AFP-high (sAFP-H) and serum AFP-normal (sAFP-N) by serum AFP levels, and into GAPEP (expressing AFP, GPC3, or SALL4) and non-GAPEP (nGAPEP) by AFP/GPC3/SALL4 immunohistochemistry results. We also collected 12 non-resected gastric adenocarcinoma patients with serum AFP ≥ 7 ng/mL before treatment (group B). We analyzed these patients' clinicopathological characteristics and prognoses.Results: Seventeen (4.04%) patients in group A were sAFP-H. These patients were younger and mainly had tubular adenocarcinoma with later pT (P = 0.014) and pN (P = 0.047) categories and more lymphovascular invasion (P < 0.001), perineural spread (P = 0.008), and metastases or recurrence (P < 0.001). For immunohistochemistry, 34 (8.08%) cases were GAPEP, and GAPEP cases also had later pT categories than nGAPEP cases (P = 0.001). Most group B patients with elevated serum AFP (especially > 1000 ng/mL) had simultaneous metastases, mainly liver metastases. Both the serological method and immunohistochemical method were useful for predicting prognosis (AUC sAFP = 0.625, AUC A/G/S-IHC = 0.723, z statistic = 1.726, P = 0.084). The serum AFP level (especially > 1000 ng/mL) is more specific (100%), and immunohistochemistry is more sensitive (50%).Conclusion: Both the serum AFP level and immunohistochemical expression of AFP/GPC3/SALL4 can be used to indicate a poor prognosis for gastric adenocarcinoma. [ABSTRACT FROM AUTHOR]

Background: Novel coronavirus disease 2019 (COVID-19) causes an immense disease burden. Although public health countermeasures effectively controlled the epidemic in China, non-pharmaceutical interventions can neither be maintained indefinitely nor conveniently implemented globally. Vaccination is mainly used to prevent COVID-19, and most current antiviral treatment evaluations focus on clinical efficacy. Therefore, we conducted population-based simulations to assess antiviral treatment effectiveness among different age groups based on its clinical efficacy. Methods: We collected COVID-19 data of Wuhan City from published literature and established a database (from 2 December 2019 to 16 March 2020). We developed an age-specific model to evaluate the effectiveness of antiviral treatment in patients with COVID-19. Efficacy was divided into three types: (1) viral activity reduction, reflected as transmission rate decrease [reduction was set as v (0–0.8) to simulate hypothetical antiviral treatments]; (2) reduction in the duration time from symptom onset to patient recovery/removal, reflected as a 1/γ decrease (reduction was set as 1–3 days to simulate hypothetical or real-life antiviral treatments, and the time of asymptomatic was reduced by the same proportion); (3) fatality rate reduction in severely ill patients (fc) [reduction (z) was set as 0.3 to simulate real-life antiviral treatments]. The population was divided into four age groups (groups 1, 2, 3 and 4), which included those aged ≤ 14; 15–44; 45–64; and ≥ 65 years, respectively. Evaluation indices were based on outbreak duration, cumulative number of cases, total attack rate (TAR), peak date, number of peak cases, and case fatality rate (f). Results: Comparing the simulation results of combination and single medication therapy s, all four age groups showed better results with combination medication. When 1/γ = 2 and v = 0.4, age group 2 had the highest TAR reduction rate (98.48%, 56.01–0.85%). When 1/γ = 2, z = 0.3, and v = 0.1, age group 1 had the highest reduction rate of f (83.08%, 0.71–0.12%). Conclusions: Antiviral treatments are more effective in COVID-19 transmission control than in mortality reduction. Overall, antiviral treatments were more effective in younger age groups, while older age groups showed higher COVID-19 prevalence and mortality. Therefore, physicians should pay more attention to prevention of viral spread and patients deaths when providing antiviral treatments to patients of older age groups. [ABSTRACT FROM AUTHOR]

Temporomandibular disorder (TMD) is commonly comorbid with fibromyalgia syndrome (FMS). The incidence of these pain conditions is prevalent in women and prone to mental stress. Chronic pain symptoms in patients with FMS and myofascial TMD (mTMD) are severe and debilitating. In the present study, we developed a new animal model to mimic the comorbidity of TMD and FMS. In ovariectomized female rats, repeated forced swim (FS) stress induced mechanical allodynia and thermal hyperalgesia in the hindpaws of the 17β-estradiol (E2) treated rats with orofacial inflammation. Subcutaneous injection of E2, injection of complete Freund's adjuvant (CFA) into masseter muscles or FS alone did not induce somatic hyperalgesia. We also found that the somatic hyperalgesia was accompanied by upregulation of GluN1 receptor and serotonin (5-hydroxytryptamine, 5-HT)3A receptor expression in the dorsal horn of spinal cord at L4-L5 segments. Intrathecal injection of N-methyl-D-aspartic acid receptor (NMDAR) antagonist 2-amino-5-phosphonovaleric acid (APV) or 5-HT3 receptor antagonist Y-25130 blocked stress-induced wide-spreading hyperalgesia. These results suggest that NMDAR-dependent central sensitization in the spinal dorsal horn and 5-HT-dependent descending facilitation contribute to the development of wide-spreading hyperalgesia in this comorbid pain model. [ABSTRACT FROM AUTHOR]

Background: Microvascular invasion (MVI) is considered to be one of the important prognostic factors that affect postoperative recurrence in patients with hepatocellular carcinoma (HCC) with variable results across their treatment options. This study was carried out to investigate efficacy of postoperative adjuvant RT in HCC patients with MVI.Methods: This was single center, prospective study carried out in HCC patients with MVI, aged 35-72 years. All patients were non-randomly allocated to receive standard postoperative treatment of HBV/HCV and nutritional therapy or RT in addition to standard postoperative treatment (1:1). The primary endpoints assessed were relapse-free survival and overall survival. The prognostic factors associated with survival outcomes were also analyzed. The safety events were graded according to NCI-CTCAE v4.03 criteria.Results: Of the 115 patients eligible for study, 59 patients were included in analysis. Univariate analysis revealed that MVI classification (P = 0.009), post-operative treatment strategies (P = 0.009) were prognostic factors for worst RFS; tumor size (P = 0.011), MVI classification (P = 0.005) and post-operative treatment (P = 0.015) were associated for OS. The 1-, 2-, 3-year RFS rates were 86.2, 70.5 and 63.4% for patients in RT group, and 46.4, 36.1, and 36.1% in control group. For OS, corresponding rates were 96.6, 80.7, and 80.7% for patients in RT group and 79.7, 58.3, and 50.0% in control group. Subgroup classification of HCC patients according to low risk MVI showed significantly longer RFS (P = 0.035) and OS (P = 0.004) in RT group than control group, while for high risk MVI, RT depicted longer OS than control group with no significance (P = 0.106). Toxicities were usually observed in acute stage with no grade 4 toxicities.Conclusion: Postoperative adjuvant RT following hepatectomy offers better RFS for HCC patients with MVI than with standard postoperative therapy. Also, it will be useful to control microscopic lesions in both M1 (low risk) and M2 (high risk) subgroups of HCC patients with MVI.Trial Registration: Trial Registration number: ChiCTR1800017371 . Date of Registration: 2018-07-26. Registration Status: Retrospectively registered. [ABSTRACT FROM AUTHOR]

Background: It has recently been reported that intermittent fasting shapes the gut microbiota to benefit health, but this effect may be influenced to the exact fasting protocols. The purpose of this study was to assess the effects of different daily fasting hours on shaping the gut microbiota in mice. Healthy C57BL/6 J male mice were subjected to 12, 16 or 20 h fasting per day for 1 month, and then fed ad libitum for an extended month. Gut microbiota was analyzed by 16S rRNA gene-based sequencing and food intake was recorded as well. Results: We found that cumulative food intake was not changed in the group with 12 h daily fasting, but significantly decreased in the 16 and 20 h fasting groups. The composition of gut microbiota was altered by all these types of intermittent fasting. At genus level, 16 h fasting led to increased level of Akkermansia and decreased level of Alistipes, but these effects disappeared after the cessation of fasting. No taxonomic differences were identified in the other two groups. Conclusions: These data indicated that intermittent fasting shapes gut microbiota in healthy mice, and the length of daily fasting interval may influence the outcome of intermittent fasting. [ABSTRACT FROM AUTHOR]

Background: Apolipoprotein M (apoM) was the carrier of the biologically active lipid mediator sphingosine-1-phospate in high density lipoprotein cholesterol (HDL-C) and played a critical role in formation and maturation of prebeta-HDL-C particles. The plasma apoM levels were decreased obviously in patients with type 2 diabetes mellitus (T2DM). A new single-nucleotide polymorphism (SNP) C-724del in apoM promoter was associated with a higher risk for coronary artery diseases (CAD) and myocardial infarction, could reduce promoter activities and apoM expression in vitro. The primary aim of the present case-controls study was to investigate the effect of apoM SNP C-724del on apoM expression in vivo and its association with T2DM susceptibility in an eastern Han Chinese cohort. Methods: Two hundred and fifty-nine T2DM patients and seventy-six healthy controls were included in this study. Amplifying DNA of apoM proximal promoter region including SNP C-724del by Real-Time Polymerase Chain Reaction (RT-PCR) and amplicons sequencing. The plasma apoM concentrations were assayed by enzyme linked immunosorbentassay (ELISA). Results: Four polymorphic sites, rs805297 (C-1065A), rs9404941 (T-855C), rs805296 (T-778C), C-724del were confirmed. rs805297 (C-1065A) and rs9404941 (T-855C) showed no statistical difference in allele frequencies and genotype distributions between T2DM patients and healthy controls just as previous studies. It's worth noting that the difference of rs805296 (T-778C) between these two groups was not found in this study. In SNP C-724del, the frequency of del allele and mutant genotypes (del/del, C/del) were higher in T2DM patients compared with healthy controls (p = 0.035; P = 0.040, respectively), while the plasma apoM levels of C-724del mutant allele carriers compared with the wide-type homozygotes carriers were not statistically different in T2DM patients (18.20 ± 8.53 ng/uL vs 20.44 ± 10.21 ng/uL, P = 0.245). Conclusion: The polymorphism C-724del in the promoter region of the apoM gene could confer the risk of T2DM among eastern Han Chinese. Unfortunately, the lowing of plasma apoM levels of C-724del mutant allele carriers compared with the wide-type homozygotes carriers in T2DM patients was not statistically different in present study, so further researchs were needed by enlarging the sample. [ABSTRACT FROM AUTHOR]

Background: Berberine (BBR) is a drug with multiple effects on cellular energy metabolism. The present study explored answers to the question of which CYP450 (Cytochrome P450) isoenzymes execute the phase-I transformation for BBR, and what are the bioactivities of its metabolites on energy pathways.Methods: BBR metabolites were detected using LC-MS/MS. Computer-assistant docking technology as well as bioassays with recombinant CYP450s were employed to identify CYP450 isoenzymes responsible for BBR phase-I transformation. Bioactivities of BBR metabolites in liver cells were examined with real time RT-PCR and kinase phosphorylation assay.Results: In rat experiments, 4 major metabolites of BBR, berberrubine (M1), thalifendine (M2), demethyleneberberine (M3) and jatrorrhizine (M4) were identified in rat's livers using LC-MS/MS (liquid chromatography-tandem mass spectrometry). In the cell-free transformation reactions, M2 and M3 were detectable after incubating BBR with rCYP450s or human liver microsomes; however, M1 and M4 were below detective level. CYP2D6 and CYP1A2 played a major role in transforming BBR into M2; CYP2D6, CYP1A2 and CYP3A4 were for M3 production. The hepatocyte culture showed that BBR was active in enhancing the expression of insulin receptor (InsR) and low-density-lipoprotein receptor (LDLR) mRNA, as well as in activating AMP-activated protein kinase (AMPK). BBR's metabolites, M1-M4, remained to be active in up-regulating InsR expression with a potency reduced by 50-70%; LDLR mRNA was increased only by M1 or M2 (but not M3 and M4) with an activity level 35% or 26% of that of BBR, respectively. Similarly, AMPK-α phosphorylation was enhanced by M1 and M2 only, with a degree less than that of BBR.Conclusions: Four major BBR metabolites (M1-M4) were identified after phase-I transformation in rat liver. Cell-free reactions showed that CYP2D6, CYP1A2 and CYP3A4 seemed to be the dominant CYP450 isoenzymes transforming BBR into its metabolites M2 and M3. BBR's metabolites remained to be active on BBR's targets (InsR, LDLR, and AMPK) but with reduced potency. [ABSTRACT FROM AUTHOR]

Background: Ovarian cancer during pregnancy is relatively rare and treatment strategies are inexperienced in surgery and chemotherapy. Multidisciplinary management of advanced epithelial ovarian cancer in pregnant patients with strong desire of fertility including sufficient mental and medical understanding, perioperative consideration, intraoperative decision, chemotherapy sensitivity and follow-up after treatment can gain successful outcomes for both maternal disease and fetus's development. Case presentation: A 34-year-old primigravidae was diagnosed with advanced epithelial ovarian tumor and then first cytoreductive surgery to resect macroscopical lesions and protect the uterus for fetus was performed following with four chemotherapy courses (docetaxel and carboplatin) before delivery and four other chemotherapy courses after delivery. Chemotherapy drugs were decided by sensitivity test and the patient's anaphylaxis. Second surgery involved cesarean section with a healthy offspring and secondary cytoreductive surgery. Operative strategies were considered to gain a balance of disease and risk for fetus. Psychosocial support was provided during the course of diagnosis and treatment for a healthy coping situation. This patient relapsed 19 months after the last chemotherapy course and was treated by additional adjuvant therapy to a clinical remission. The 33-month baby boy has no evidence with disease until now. The follow-up of both mother and baby is still continuing. Conclusions: Ovarian cancer during pregnancy has low incidence which must increase in future as women delay reproduction age. Ovarian cancer cytoreductive surgery and chemotherapy have limitation to handle conditions under a desire of fetus protection. Multidisciplinary treatment model is a therapeutic solution and a challenge for gynecological surgeons, medical oncologists, pathologists, obstetricians, neonatologists, pharmacists, anesthetist, and psychologists. [ABSTRACT FROM AUTHOR]