The prophylaxis functions of Lactobacillus fermentum GLF-217 and Lactobacillus plantarum FLP-215 on ulcerative colitis via modulating gut microbiota of mice.

BACKGROUND: The strong connection between gut microbes and human health has been confirmed by an increasing number of studies. Although probiotics have been found to relieve ulcerative colitis, the mechanism varies by the species involved. In this study, the physiological, immune and pathological factors of mice were measured and shotgun metagenomic sequencing was conducted to investigate the potential mechanisms in preventing ulcerative colitis. RESULTS: The results demonstrated that ingestion of Lactobacillus fermentum GLF-217 and Lactobacillus plantarum FLP-215 significantly alleviated ulcerative colitis induced by dextran sulfate sodium (DSS), as evidenced by the increase in body weight, food intake, water intake and colon length as well as the decrease in disease activity index, histopathological score and inflammatory factor. Both strains not only improved intestinal mucosa by increasing mucin-2 and zonula occludens-1, but also improved the immune system response by elevating interleukin-10 levels and decreasing the levels of interleukin-1ß, interleukin-6, tumor necrosis factor-α and interferon-γ. Moreover, L. fermentum GLF-217 and L. plantarum FLP-215 play a role in preventing DSS-induced colitis by regulating the structure of gut microbiota and promoting the formation of short-chain fatty acids. CONCLUSIONS: This study may provide a reference for the prevention strategy of ulcerative colitis. © 2024 Society of Chemical Industry.

[Ligusticum cycloprolactam inhibits IL-1ß-induced apoptosis and inflammation of rat chondrocytes via HMGB1/TLR4/NF-κB signaling pathway].

Chondrocytes are unique resident cells in the articular cartilage, and the pathological changes of them can lead to the occurrence of osteoarthritis(OA). Ligusticum cycloprolactam(LIGc) are derivatives of Z-ligustilide(LIG), a pharmacodynamic marker of Angelica sinensis, which has various biological functions such as anti-inflammation and inhibition of cell apoptosis. However, its protective effect on chondrocytes in the case of OA and the underlying mechanism remain unclear. This study conducted in vitro experiments to explore the molecular mechanism of LIGc in protecting chondrocytes from OA. The inflammation model of rat OA chondrocyte model was established by using interleukin-1ß(IL-1ß) to induce. LIGc alone and combined with glycyrrhizic acid(GA), a blocker of the high mobility group box-1 protein(HMGB1)/Toll-like receptor 4(TLR4)/nuclear factor-kappa B(NF-κB) signaling pathway, were used to intervene in the model, and the therapeutic effects were systematically evaluated. The viability of chondrocytes treated with different concentrations of LIGc was measured by the cell counting kit-8(CCK-8), and the optimal LIGc concentration was screened out. Annexin V-FITC/PI apoptosis detection kit was employed to examine the apoptosis of chondrocytes in each group. The enzyme-linked immunosorbent assay(ELISA) was employed to measure the expression of cyclooxygenase-2(COX-2), prostaglandin-2(PGE2), and tumor necrosis factor-alpha(TNF-α) in the supernatant of chondrocytes in each group. Western blot was employed to determine the protein levels of B-cell lymphoma-2(Bcl-2), Bcl-2-associated X protein(Bax), caspase-3, HMGB1, TLR4, and NF-κB p65. The mRNA levels of HMGB1, TLR4, NF-κB p65, and myeloid differentiation factor 88(MyD88) in chondrocytes were determined by real-time fluorescent quantitative PCR(RT-qPCR). The safe concentration range of LIGc on chondrocytes was determined by CCK-8, and then the optimal concentration of LIGc for exerting the effect was clarified. Under the intervention of IL-1ß, the rat chondrocyte model of OA was successfully established. The modeled chondrocytes showed increased apoptosis rate, promoted expression of COX-2, PGE2, and TNF-α, up-regulated protein levels of Bax, caspase-3, HMGB1, TLR4, and NF-κB p65 and mRNA levels of HMGB1, TLR4, NF-κB p65, and MyD88, and down-regulated protein level of Bcl-2. However, LIGc reversed the IL-1ß-induced changes of the above factors. Moreover, LIGc combined with GA showed more significant reversal effect than LIGc alone. These fin-dings indicate that LIGc extracted and derived from the traditional Chinese medicine A. sinensis can inhibit the inflammatory response of chondrocytes and reduce the apoptosis of chondrocytes, and this effect may be related to the HMGB1/TLR4/NF-κB signaling pathway. The pharmacological effect of LIGc on protecting chondrocytes has potential value in delaying the progression of OA and improving the clinical symptoms of patients, and deserves further study.

Endoscopic Surveillance for Premalignant Esophageal Lesions: A Community-Based Multicenter, Prospective Cohort Study.

BACKGROUND & AIMS: Mild and moderate dysplasia are major premalignant lesions of esophageal squamous cell carcinoma (ESCC); however, evidence of the progression risk in patients with these conditions is extremely limited. We aimed to assess the incidence and risk factors for advanced neoplasia in patients with mild-moderate dysplasia. METHODS: This prospective cohort study included patients with mild-moderate dysplasia from 9 regions in rural China. These patients were identified from a community-based ESCC screening program conducted between 2010 and 2016 and were offered endoscopic surveillance until December 2021. We estimated the incidence of advanced esophageal neoplasia, including severe dysplasia, carcinoma in situ, or ESCC, and identified potential risk factors using the Cox regression model. RESULTS: The 1183 patients with mild-moderate dysplasia were followed up over a period of 6.95 years. During follow-up evaluation, 88 patients progressed to advanced neoplasia (7.44%), with an incidence rate of 10.44 per 1000 person-years. The median interval from the progression of mild-moderate dysplasia to advanced neoplasia was 2.39 years (interquartile range, 1.58-4.32 y). A total of 74.47% of patients with mild-moderate dysplasia experienced regression to nondysplasia, and 18.09% showed no lesion progression. Patients with mild-moderate dysplasia who had a family history of esophageal cancer and were age 55 years and older showed 97% higher advanced neoplasia yields than all patients with mild-moderate dysplasia. CONCLUSIONS: In a country with a high incidence of ESCC, patients with mild-moderate dysplasia showed an overall risk of advanced neoplasia progression of 1.04% per year. Patients with mild-moderate dysplasia would be recommended for endoscopic surveillance during the first 2 to 3 years.

Association between glycated haemoglobin and the risk of chronic obstructive pulmonary disease: A prospective cohort study in UK biobank.

AIMS: To investigate the association between glycated haemoglobin (HbA1c) levels and chronic obstructive pulmonary disease (COPD) incidents in the general population, and the association between HbA1c levels and mortality in patients with COPD. MATERIALS AND METHODS: We investigated the association of HbA1c levels with COPD risk in the general population in the UK Biobank, using data from 420 065 participants. Survival analysis was conducted for 18 854 patients with COPD. We used restricted cubic spline analysis to assess the dose-response relationship between HbA1c levels and COPD risk and survival. Cox proportional hazards regression models were used to estimate hazard ratios (HRs) with 95% confidence intervals (CIs). RESULTS: During a median follow-up of 12.3 years, 11 556 COPD cases were recorded. HbA1c had a non-linear relationship with COPD risk (p for non-linearity < .05). Compared with the quintile 2 (32.2-<34.3 mmol/mol), those with HbA1c levels above 38.7 mmol/mol (quintile 5) had a 22% (HR, 1.22, 95% CI: 1.15-1.30) higher risk of COPD. Compared with the HbA1c decile 2 (30.5-<32.2 mmol/mol), the HRs (95% CI) of COPD risk were 1.16 (1.03-1.30) and 1.36 (1.24-1.50) in the lowest HbA1c decile (<30.5 mmol/mol) and highest decile (≥41.0 mmol/mol), respectively. The increased COPD risk associated with HbA1c was more pronounced in younger, current smokers, passive smokers, and participants with a higher Townsend deprivation index (all p for interaction < .05). Among patients with COPD, 4569 COPD cases died (488 because of COPD) during a median follow-up of 5.4 years. Regarding COPD survival, HbA1c had a non-linear relationship with all-cause death (p for non-linearity < .05). Those with HbA1c quintile 5 (≥38.7 mmol/mol) had a 23% (HR, 1.23, 95% CI: 1.10-1.37) higher risk of all-cause death compared with the quintile 2 (32.2-<34.3 mmol/mol). Compared with the HbA1c decile 4 (33.3-<34.3 mmol/mol), those in the lowest HbA1c decile (<30.5 mmol/mol) and highest HbA1c decile (≥41.0 mmol/mol) had 22% (HR, 1.22; 95% CI: 1.01-1.47) and 28% (HR, 1.28; 95% CI: 1.11-1.48) higher risk for overall death. However, no significant association was observed between HbA1c levels and the risk of COPD-specific death. CONCLUSIONS: Our findings indicated that lower and higher HbA1c levels were associated with a higher risk of COPD. In COPD cases, lower and higher HbA1c levels were associated with a higher COPD all-cause death risk.

Dimethyl Fumarate Protects against Lipopolysaccharide- (LPS-) Induced Sepsis through Inhibition of NF-κB Pathway in Mice.

Sepsis is one of the most severe complications and causes of mortality in the clinic. It remains a great challenge with no effective treatment for clinicians worldwide. Inhibiting the release of proinflammatory cytokines during sepsis is considered as an important strategy for treating sepsis and improving survival. In the present study, we have observed the effect of dimethyl fumarate (DMF) on lipopolysaccharide- (LPS-) induced sepsis and investigated the possible mechanism. By screening a subset of the Johns Hopkins Drug Library, we identified DMF as a novel inhibitor of nitric oxide synthesis in LPS-stimulated RAW264.7 cells, suggesting that DMF could be a potential drug to treat sepsis. To further characterize the effect of DMF on LPS signaling, TNF-α, MCP-1, G-CMF, and IL-6 expression levels were determined by using cytokine array panels. In addition, an endotoxemia model with C57BL/6 mice was used to assess the in vivo efficacy of DMF on sepsis. The survival rate was assessed, and HE staining was performed to investigate histopathological damage to the organs. DMF was found to increase the survival of septic mice by 50% and attenuate organ damage, consistent with the reduction in IL-10, IL-6, and TNF-α (inflammatory cytokines) in serum. In vitro experiments revealed DMF's inhibitory effect on the phosphorylation of p65, IκB, and IKK, suggesting that the primary inhibitory effects of DMF can be attributed, at least in part, to the inhibition of phosphorylation of IκBα, IKK as well as nuclear factor-κB (NF-κB) upon LPS stimulation. The findings demonstrate that DMF dramatically inhibits NO and proinflammatory cytokine production in response to LPS and improves survival in septic mice, raising the possibility that DMF has the potential to be repurposed as a new treatment of sepsis.

NaCdSb: An Orthorhombic Zintl Phase with Exceptional Intrinsic Thermoelectric Performance.

Many Zintl phases are promising thermoelectric materials owning to their features like narrow band gaps, multiband behaviors, ideal charge transport tunnels, and loosely bound cations. Herein we show a new Zintl phase NaCdSb with exceptional intrinsic thermoelectric performance. Pristine NaCdSb exhibits semiconductor behaviors with an experimental hole concentration of 2.9×1018  cm-3 and a calculated band gap of 0.5 eV. As the temperature increases, the hole concentration rises gradually and approaches its optimal one, leading to a high power factor of 11.56 µW cm-1 K-2 at 673 K. The ultralow thermal conductivity is derived from the small phonon group velocity and short phonon lifetime, ascribed to the structural anharmonicity of Cd-Sb bonds. As a consequence, a maximum zT of 1.3 at 673 K has been achieved without any doping optimization or structural modification, demonstrating that NaCdSb is a remarkable thermoelectric compound with great potential for performance improvement.

Assessment of the compliance, influencing factors, and yielding results of liver cancer screening in a high-risk population: A cross-sectional study.

BACKGROUND: The participation and results for liver cancer screening are rarely reported. The aim of this study was to determine the participation rates and factors affecting participation rates as well as to report the detection rate for liver cancer in an organized screening program. METHODS: The organized screening program for liver cancer was conducted in 12 rural sites. The risk of developing liver cancer was initially evaluated for each participant. High-risk individuals were offered α-fetoprotein measurement and ultrasonography examination. Potential risk factors associated with the participation rate were screened by fitted generalized linear mixed logistic regression models through reporting odds ratios (ORs) with 95% CIs. RESULTS: A total of 358,662 eligible participants completed the basic surveys, and 54,745 were evaluated to be at high risk of liver cancer. Of these high-risk individuals, 40,543 accepted the screening services. Determinants of participation for screening behavior included older age, being female, being positive for hepatitis B surface antigen, having a family history of liver cancer, chronic depression, and low income. The detection rate for liver cancer was estimated to be 0.41% (95% CI, 0.35-0.48). CONCLUSIONS: This study reported several significant factors associated with the screening behaviors for liver cancer. LAY SUMMARY: Participation rate and results for liver cancer screening in rural areas are rarely reported. The determinants associated with adherence rates and early detection rate of liver cancer in an organized screening program for liver cancer were assessed. A possible positive correlation between the participation rates and the early detection rate was observed among attendees of screening. These new finds could be beneficial to increasing the participation rate of screening.

Fresh fruit consumption, physical activity, and five-year risk of mortality among patients with type 2 diabetes: A prospective follow-up study.

BACKGROUND AND AIMS: We explored the associations among fruit consumption, physical activity, and their dose-response relationship with all-cause and cardiovascular disease (CVD) mortality in type 2 diabetic patients. METHODS AND RESULTS: We prospectively followed 20,340 community-dwelling type 2 diabetic patients aged 21-94 years. Information on diets and physical activity was collected using standardized questionnaires. All-cause and CVD mortality were assessed. Hazard ratios (HRs) for all-cause mortality were estimated with Cox regression models, and HRs for CVD mortality were derived from a competing risk model. Restricted cubic spline regression was used to analyze dose-response relationships. We identified 1362 deaths during 79,844 person-years. Compared to non-consumption, fruit consumption >42.9 g/d was inversely associated with all-cause mortality (HR 0.76; 95% CI 0.64-0.88), CVD mortality (HR 0.69, 0.51-0.94) and stroke mortality (HR 0.57, 0.36-0.89), but not with heart disease mortality (HR 0.93, 0.56-1.52). The HRs comparing the top vs bottom physical activity quartiles were 0.44 (0.37-0.53) for all-cause mortality, 0.46 (0.33-0.64) for CVD mortality, 0.46 (0.29-0.74) for stroke mortality and 0.51 (0.29-0.88) for heart disease mortality. Lower fruit consumption combined with a lower physical activity level was associated with a greater mortality risk. A nonlinear threshold of 80 g fruit/day was identified; all-cause mortality risk was reduced by approximately 24% at this value. A physical activity threshold of eight metabolic equivalents (MET) h/day was also identified, after which the risk of mortality did not decrease. CONCLUSIONS: Fruit consumption and physical activity may reduce all-cause, CVD, and stroke mortality in type 2 diabetic patients.

Ablative fractional carbon dioxide laser improves quality of life in patients with extensive burn scars: A nested case-control study.

BACKGROUND AND OBJECTIVES: Ablative fractional carbon dioxide laser (CO2 -AFL) for small-area burn scar management shows encouraging outcomes. Few studies, however, focused on comprehensive outcomes following CO2 -AFL treatment for extensive burn scars. This study evaluated whether CO2 -AFL surgery improved the quality of life (QoL) for burn survivors with extensive hypertrophic scars. METHODS: A retrospective nested case-control study was initiated to analyze the efficacy of CO2 -AFL treatment for patients with large-area burn scars. Patients with extensive burn scars (≥30% total body surface area [TBSA]) were registered in our hospital from March 2016 to October 2018. Patients undergoing CO2 -AFL surgery were divided into CO2 -AFL group, and patients undergoing conventional surgery were matched in a 1:1 ratio as the conventional surgery group according to the burned area. The questionnaires were collected and followed up. The 36-Item Short Form Health Survey (SF-36) and Burns Specific Health Scale-Brief (BSHS-B) were the primary parameters. Secondary parameters included the Pittsburgh Sleep Quality Index (PSQI), University of North Carolina "4P" Scars Scale (UNC4P), Patient Scars Assessment Scale for Patient (POSAS-P), and Douleur Neuropathique 4 questions (DN4). RESULTS: 23 patients (55.96 ± 21.59% TBSA) were included in CO2 -AFL group and 23 patients (57.87 ± 18.21% TBSA) in conventional surgery group. Both the BSHS-B total score (CO2 -AFL vs. conventional surgery: 115.35 ± 29.24 vs. 85.43 ± 33.19, p = 0.002) and the SF-36 total score (CO2 -AFL vs. conventional surgery: 427.79 ± 118.27 vs. 265.65 ± 81.66, p < 0.001) for the CO2 -AFL group were higher than those for the conventional surgery group. Parameters for the CO2 -AFL group were lower than those for the conventional surgery group in all of the following comparisons: PSQI total score (CO2 -AFL vs. conventional surgery: 7.70 ± 3.74 vs. 12.26 ± 4.61, p = 0.001), POSAS-P total score (CO2 -AFL vs. conventional surgery: 26.48 ± 6.60 vs. 33.04 ± 4.56, p < 0.001), UNC4P total score (CO2 -AFL vs. conventional surgery: 5.57 ± 1.97 vs. 7.26 ± 1.81, p = 0.004), and DN4 score (CO2 -AFL vs. conventional surgery: 3 [2-5] vs. 5 [4-8], p = 0.004). CONCLUSIONS: Compared to conventional surgery, whole scar CO2 -AFL surgery dramatically improved physical and mental health as well as QoL for people with extensive burn scars. Additionally, CO2 -AFL enhanced the evaluation of scars including their appearance, pain, itching, and a host of other symptoms.

A WeChat-based competency and performance checklist in basic surgical skills course for military medical academy undergraduates.

BACKGROUND: Basic surgical skills (BSS) is a key bridging course for medical students to acquire basic surgical maneuvers and practice animal surgery before clinical rotation, but the complexity of operational procedures and high demands on asepsis may lead to poor performance and frequent error during practice. The current study intended to improve BSS teaching outcomes by implementing smartphone app-based competency and performance checklists for medical academy undergraduates. METHODS: WeChat-based checklists containing competency and performance modules were designed, distributed and collected via smartphone. One hundred seventy-six third-grade undergraduate cadets majoring in clinical medicine or anesthesiology were prospectively enrolled, with 92 set as study group and 84 as control group. Checklists were distributed for self-evaluation before and after each class throughout the semester of autumn 2021-2022. Student age, previous Grade Point Average (GPA), average grades of BSS (including grade-A rate and pass rate), operative time, error rate, and perioperative complications of intestinal anastomosis performed on Beagle dogs between the groups were compared to evaluate the efficacy of the checklists. RESULTS: The students aged 20.2 ± 0.63 in Group A and 20.3 ± 0.92 in Group B (P = 0.15), with a previous GPA of 2.9 ± 0.61 vs. 2.87 ± 0.58 (P = 0.61). The average operative time on their final lesson of intestinal anastomosis was 192.3 ± 27.18 min vs. 213.8 ± 29.48 min (P < 0.001). All students passed in BSS course, with a final grade of 89.45 ± 4.360 in Group A and 86.64 ± 4.026 in Group B (P < 0.001), in which grade-A rate was 46.7% vs. 26.2% (P = 0.005). For perioperative comorbidities, 4/23 (17.4%) animals in Group A and 5/21 (23.8%) in Group B recorded wound dehiscence or other incision-related complications; no animals died in Group A, and 2 died in Group B due to hemorrhagic shock or sepsis. CONCLUSIONS: The implementation of WeChat-based checklist is a reflection of improved quality of teaching in BSS course that may promote the students' competency and performance.

The Defects of Epigenetic Reprogramming in Dox-Dependent Porcine-iPSCs.

Porcine-induced pluripotent stem cells (piPSCs) are of great significance to animal breeding and human medicine; however, an important problem is that the maintenance of piPSCs mainly depends on exogenous expression of pluripotent transcription factors (TFs), and germline transmission-competent piPSCs have not yet been successfully established. In this study, we explore the defect of epigenetic reprogramming during piPSCs formation, including chromatin accessibility, DNA methylation, and imprinted gene expression, with high-throughput sequencing (ATAC-seq, WGBS, RNA-seq, and Re-seq) methods. We found the somatic features were successfully silenced by connecting closed chromatin loci with downregulated genes, while DNA methylation has limited effects on somatic silence. However, the incomplete chromatin remodeling and DNA demethylation in pluripotency genes hinder pluripotent activation, resulting in the low expression of endogenous pluripotency genes. In addition, the expression of potential imprinted genes was abnormal, and many allelic-biased expressed genes in porcine embryonic fibroblasts (PEFs) were erased, accompanied by establishment of new allelic-biased expressed genes in piPSCs. This study reveals the aberrant epigenetic reprogramming during dox-dependent piPSCs formation, which lays the foundation for research of porcine-iPSC reprogramming and genome imprinting.

Selection of high-risk individuals for esophageal cancer screening: A prediction model of esophageal squamous cell carcinoma based on a multicenter screening cohort in rural China.

The mortality benefit of esophageal squamous cell carcinoma (ESCC) screening has been reported in several studies; however, the results of ESCC screening programs in China are suboptimal. Our study aimed to develop an ESCC risk prediction model to identify high-risk individuals for population-based esophageal cancer screening. In total, 86 745 participants enrolled in a population-based esophageal cancer screening program in rural China between 2007 and 2012 were included in the present study and followed up until December 31, 2015. Models for identifying individuals at risk of ESCC within 3 years were created using logistic regressions. The area under the receiver operating curve (AUC) was determined to estimate the model's overall performance. A total of 298 individuals were diagnosed with ESCC within 3 years after baseline. The model of ESCC included the predictors of age, sex, family history of upper gastrointestinal cancer, smoking status, alarming symptoms of retrosternal pain, back pain or neck pain, consumption of salted food and fresh fruits and disease history of peptic ulcer or esophagitis (AUC of 0.81; 95% confidence interval: 0.78-0.83). Compared to the current prescreening strategy in our program, the cut-off value of 10 in the score-based model could result in 3.11% fewer individuals subjected to endoscopies and present higher sensitivity, slightly higher specificity and lower number needed to screen. This score-based risk prediction model of ESCC based on eight epidemiological risk factors could increase the efficiency of the esophageal cancer screening program in rural China.

An initial screening strategy based on epidemiologic information in esophageal cancer screening: a prospective evaluation in a community-based cancer screening cohort in rural China.

BACKGROUND AND AIMS: In China, regional organized esophageal cancer screening programs have been implemented since 2005. However, the implementation of these screening programs is still facing some urgent challenges, especially concerning identifying high-risk individuals. This study aimed to evaluate the risk stratification potential of the current initial assessment strategy used in a mass esophageal squamous cell carcinoma (ESCC) screening program in China. METHODS: A total of 43,875 participants without a previous cancer history enrolled in a mass ESCC screening program in China from 2007 to 2010 who had initial assessment results were included in this study and were followed until December 31, 2015. Eight potential risk factors for ESCC were evaluated in the initial assessment strategy. A comprehensive evaluation of the association of the initial assessment results with ESCC risk was performed by propensity score matching and Cox regression analysis. RESULTS: During a median follow-up of 5.5 years, 272 individuals developed ESCC. The high-risk population assessed at baseline had a higher risk of ESCC than the non-high-risk population, with a hazard ratio (HR) of 3.11 (95% confidence interval (CI), 2.33-4.14) after adjustment for sex, age, education level, income level, and body mass index. In addition, the initial assessment results of the high-risk population were significantly associated with the risk of all esophageal cancers (HR, 3.30; 95% CI, 2.51-4.33) and upper gastrointestinal cancers (HR, 3.03; 95% CI, 2.43-3.76). CONCLUSIONS: The initial screening tool in a mass ESCC screening program in China, consisting of 8 accessible variables in epidemiologic surveys, could be helpful for the selection of asymptomatic individuals for priority ESCC screening.

Association of cancer awareness levels with the risk of cancer in rural China: A population-based cohort study.

BACKGROUND: Evidence of the effects of cancer prevention knowledge on the risk of developing cancer remains scarce. The objective of this study was to prospectively examine the association of cancer prevention awareness levels with cancer risk in a population-based cancer screening cohort in China. METHODS: This prospective cohort study included 164,341 participants aged 40 to 69 years with no history of cancer and with available information on cancer prevention core knowledge in the Esophageal, Stomach, and Liver Cancer Screening Program. Participants were recruited from 18 rural regions across 4 provinces in China from 2007 to 2014 and were followed until December 31, 2015. The core knowledge of cancer prevention content included 9 items, with a total score ranging from 0 to 100. Cox proportional hazards regression models and restricted cubic spline analysis were used to estimate hazard ratios and 95% CIs. RESULTS: High cancer prevention knowledge scores were inversely associated with the overall risk of cancer (group 4 vs group 1: hazard ratio, 0.669; 95% CI, 0.576-0.776). Subgroup analysis showed that this inverse association could be observed in women, participants with lower educational or income levels, and those without a family history of cancer. Restricted cubic spline analysis exhibited a nonlinear (L-shaped) relation between cancer knowledge scores and cancer risk (overall P < .0001; nonlinear P = .0141). CONCLUSIONS: The main finding of this prospective study was that higher levels of cancer prevention awareness could be associated with a relative reduction in the risk of developing cancer.

Development of a PHMB hydrogel-modified wound scaffold dressing with antibacterial activity.

Current wound scaffold dressing constructs can facilitate wound healing but do not exhibit antibacterial activity, resulting in high infection rates. We aimed to endow wound scaffold dressing with anti-infective ability by polyhexamethylenebiguanide (PHMB). We prepared PHMB hydrogel at varying concentrations (0.25%, 0.5%, 1%, 2%) and assessed release and cytotoxicity. PHMB hydrogel was added to the wound scaffold dressing to generate a PHMB hydrogel-modified wound scaffold dressing. Wound healing and infection prevention were evaluated using a full-thickness skin defect model in rats. In vitro, the hydrogel PHMB release time positively correlated with PHMB concentration, with 1% allowing sufficiently long release time to encompass the high-incidence period (3-5 days) of infection following wound scaffold dressing implantation. Implantation of 1% PHMB hydrogel into the skin did not cause adverse responses. in vitro cytotoxicity assays showed the PHMB hydrogel-modified wound scaffold dressing did not significantly affect proliferation of fibroblasts or vascular endothelial cells, 99.90% vs 99.84% for fibroblasts and 100.21% vs 99.28% for vascular endothelial cells at 21 days. Transplantation of PHMB hydrogel-modified wound scaffold dressing/unmodified wound scaffold dressing on the non-infected wounds of rats yielded no significant difference in relative vascularization rate, 47.40 vs 50.87 per view at 21 days, whereas bacterial content of the wound tissue in the PHMB hydrogel-modified wound scaffold dressing group was significantly lower than the unmodified wound scaffold dressing group, (1.80 ± 0.35) × 103 vs (9.34 ± 0.45) × 103 at 14 days. Prevalence of persistent wound infection in the rats receiving PHMB hydrogel-modified wound scaffold dressing transplantation onto infected wounds was significantly lower than the unmodified wound scaffold dressing group, 30% vs 100%. PHMB hydrogel-modified wound scaffold dressing exhibited suitable antibacterial ability, and its biological activity did not significantly differ from that of the unmodified wound scaffold dressing, thereby allowing it to effectively prevent infection following wound scaffold dressing implantation.

MTHFR C677T genetic polymorphism in combination with serum vitamin B2, B12 and aberrant DNA methylation of P16 and P53 genes in esophageal squamous cell carcinoma and esophageal precancerous lesions: a case-control study.

BACKGROUND: The study aimed to explore the associations between the interactions of serum vitamin B2 or B12 levels, aberrant DNA methylation of p16 or p53 and MTHFR C677T polymorphism and the risks of esophageal squamous cell carcinoma (ESCC) and esophageal precancerous lesion (EPL). METHODS: 200 ESCC cases, 200 EPL cases and 200 normal controls were matched by age (± 2 years) and gender. Serum vitamin B2 and B12 levels, MTHFR C677T genetic polymorphisms and the methylation status of genes were assessed. Chi square test, one-way analysis of variance and binary logistic regression were performed. RESULTS: The lowest quartile of both serum vitamin B2 and B12 with TT genotype showed significant increased EPL risk (OR = 4.91, 95% CI 1.31-18.35; OR = 6.88, 95% CI 1.10-42.80). The highest quartile of both serum vitamin B2 and B12 with CC genotype showed significant decreased ESCC risk (OR = 0.16, 95% CI 0.04-0.60; OR = 0.10, 95% CI 0.02-0.46). The ORs of p16 methylation for genotype CT and TT were 1.98 (95% CI 1.01-3.89) and 17.79 (95% CI 2.26-140.22) in EPL, 4.86 (95% CI 2.48-9.50) and 20.40 (95% CI 2.53-164.81) in ESCC, respectively. Similarly, p53 methylation with genotype TT was associated with increased EPL and ESCC risks (OR = 13.28, 95% CI 1.67-105.70; OR = 15.24, 95% CI 1.90-122.62). CONCLUSIONS: The MTHFR C677T genotype and serum vitamin B2 or B12 levels may interact in ways which associated with the EPL and ESCC risks. The gene-gene interaction suggested that aberrant DNA methyaltion of either p16 or p53 combined with T alleles of MTHFR was associated with increased risks of both EPL and ESCC.

Regioselectivity Switch in Palladium-Catalyzed Allenylic Cycloadditions of Allenic Esters: [4+1] or [4+3] Cycloaddition/Cross-Coupling.

The first Pd-catalyzed asymmetric allenylic [4+1] cycloaddition was successfully developed. Alternatively, tuning the Pd catalyst switched the reactivity toward an unprecedented [4+3] cycloaddition/cross-coupling. Ligands play a vital role in controlling the reaction pathway, allowing highly selective access to different products from identical substrates. Biological evaluation of the obtained compounds led to the discovery of new antitumor targets. A possible mechanism is proposed, suggesting two interesting catalytic cycles for the cycloaddition with palladium-butadienyls. This study also demonstrated the potential and utility of allenic esters as 1,4-biselectrophiles and C4 synthons for participating in cycloaddition reactions.

Therapeutic efficacy of early photobiomodulation therapy on the zones of stasis in burns: An experimental rat model study.

This study aimed to investigate the role of photobiomodulation therapy in preventing zones of stasis in burn wounds. We hypothesized that photobiomodulation therapy could promote tissue formation and release of nitric oxide (NO), and reduce inflammatory responses, thereby dilating local microvessels, reducing necrosis and apoptosis. Thirty rats were randomly divided into control group (CG) and laser group (LG). The zone of stasis was formed by applying a brass comb to the skin resulting in four rectangular burns separated by three unburned interspaces. The left side was laser wound (LW), while the right side was shielded wound (SW). The LW of LG was immediately subjected to photobiomodulation therapy, followed by once-daily 30-minutes photobiomodulation therapy sessions. Skin ultrasound and Doppler angiography analyses were used to evaluate the statuses of the zones of stasis at 1, 24, and 96 hours after injury. Harvested burn wound tissue was subjected to hematoxylin-eosin staining and HMGB1, caspase 3, and thrombomodulin immunohistochemistry, and the contents of NO and TNF-α were measured in stasis tissue. Thrombomodulin, HMGB1, and caspase 3 immunohistochemistry revealed significantly lower positive staining rates in the LW of LG rats relative to the others at 96 hours (p < 0.05), as well as a significantly higher skin blood flow relative to the others (p < 0.05). The NO content was significantly higher in the LW of LG, compared with other wounds, at 24 and 96 hours after injury (p < 0.05). The TNF-α level was significantly lower in the LW of LG than in other wounds at 96 hours (p < 0.05). Early, local photobiomodulation therapy can effectively ameliorate injury progression in the zone of stasis. However, these beneficial effects are limited to the directly irradiated sites.

Non-line-of-sight 2 × N indoor optical camera communications.

We propose, for the first time to the best of our knowledge, a novel non-line-of-sight 2×N indoor optical camera communication system, where N is the number of pixels in the camera with a unique packet structure and a detection methodology for extracting the data from the recorded video streams. A comprehensive theoretical model for the proposed system is presented. The proposed system is experimentally investigated, and the measured results show that higher International Standards Organization (ISO) levels and exposure times lead to a reduced transmit power level by 3 dB for every doubling of the exposure time and ISO at a bit error rate of 10-3. It is also shown that when the overlapping area of two interfering transmitters is larger than approximately 30% of the footprints, the data cannot be recovered.