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Abstract Background Diabetic myocardial disorder (DbMD, evidenced by abnormal echocardiography or cardiac biomarkers) is a form of stage B heart failure (SBHF) at high risk for progression to overt HF. SBHF is defined by abnormal LV morphology and function and/or abnormal cardiac biomarker concentrations. Objective To compare the evolution of four DbMD groups based on biomarkers alone, systolic and diastolic dysfunction alone, or their combination. Methods The Aldose Reductase Inhibition for Stabilization of Exercise Capacity in Heart Failure (ARISE-HF) trial was a Phase 3 randomised trial of an aldose reductase inhibitor in patients with well-controlled type 2 diabetes mellitus (T2DM). The 1858 potential participants (age 67 ± 7 years; 50% women) were screened for SBHF based on abnormal echocardiography or biomarkers (N-terminal pro-B-type natriuretic peptide ≥ 40 ng/L or high sensitivity cardiac troponin T ≥ 10 ng/L [women] and ≥ 16 ng/L [men]). Exercise capacity (peak VO2) was reduced in 669 with DbMD (age 68 ± 7, 50% women), and peak VO2 was reassessed at 15 months. Results The 1463 (79%) participants with DbMD were allocated to four clusters; 907 (49%) showed isolated elevation of cardiac biomarkers, 301 (16%) with systolic dysfunction/hypertrophy, 162 (9%) with diastolic dysfunction and 93 (5%) comprised an overlap cluster (combined diastolic, systolic or LV geometric abnormalities). Reduced VO2 (

Abstract Background and aim The system of family doctor contract services is a crucial component of China's primary healthcare system. Patients enrolled in family doctor contract services typically receive more comprehensive health services. However, it remains uncertain whether the family doctor contract services can fully meet the healthcare needs of patients. Despite extensive research on family doctor contract services, there has been relatively little investigation from the perspective of patients' sense of gain, and there are no specific tools available to measure patients' sense of gain in healthcare. Therefore, this study aims to develop a scale to measure patients' sense of gain in family doctor contract services. Methods This study enrolled 600 patients under family doctor contracts. It utilized a review of literature and Delphi expert consultation to form the concept of patients' sense of medical gain in the context of family doctor services, establish an item pool, screen items, and evaluate the scale's reliability and validity. Factor analysis assessed the scale's structural validity, while Cronbach's alpha coefficient evaluated its internal consistency. Test–retest reliability and split-half reliability were used to assess the scale's reliability. Results The Patients' Sense of Medical Gain in the context of Family Doctor services(PSMG-FD) scale for assessing sense of medical gain among family doctor contract patients comprises 19 items, categorized into five factors: Medical convenience, continuity, reliability, humanistic care, and experience. Confirmatory factor analysis results indicated satisfactory fit indices: χ2/df = 2.781, RMSEA = 0.077, RMR = 0.031, GFI = 0.875, NFI = 0.918, IFI = 0.946, TLI = 0.934, CFI = 0.945, and RFI = 0.901. The AVE values for different dimensions were 0.544, 0.739, 0.741, 0.755, and 0.654, all surpassing the threshold of 0.5. The CR values for each dimension were 0.820, 0.919, 0.919, 0.925, and 0.850, all exceeding 0.7, indicating satisfactory convergent validity. The interdimensional correlation coefficients were lower than the square roots of the corresponding AVEs, suggesting correlation among latent variables while maintaining sufficient discriminant validity. The PSMG-FD scale demonstrated good reliability and validity, with a Cronbach’s α coefficient of 0.947, test–retest reliability of 0.955, and split-half reliability of 0.895. Conclusion The scale exhibits good reliability and validity, making it a suitable instrument for evaluating sense of medical gain among family doctor contract patients in China.

Abstract Background Spinal cord injury (SCI) is a common neurological condition marked by damage to the spinal cord. In the field of neurological rehabilitation, virtual reality (VR) is increasingly employed for evaluating and addressing the physical limitations caused by SCI. This study aimed to describe and calculate the effect sizes of virtual reality intervention (VR) on the functional performance of SCI. Methods We searched PubMed, Embase, Web of Science, and Cochrane Library to identify articles published before October 30, 2023, that addressed the intervention of SCI using virtual reality technology. We excluded from the meta-analysis articles that did not provide enough data to evaluate the association between virtual reality intervention and spinal cord injury. The RevMan 5.4 statistical software was used for data analysis. Results We included 16 articles in the systematic review and pooled 9 for the meta-analysis, which were 5 randomized controlled trials (RCTs) and 4 non-RCTs, including 248 subjects. The outcome measure of the walking index for spinal cord injury, limits of stability testing and berg balance scale scores improved in non-RCTs. Conclusion VR has shown promise in enhancing walking ability and balance function in individuals with SCI. However, the existing evidence for VR interventions in SCI patients remains limited, highlighting the necessity for future studies in this area.

Abstract In this study, we dynamically monitored the glomerular filtration rate and other assessment of renal function and markers of injury in various mice models of acute kidney injury. Male C57BL/6 mice were utilized to establish acute kidney injury models of sepsis, ischemia reperfusion, cisplatin, folic acid, aristolochic acid and antibiotic. In addition to the real time glomerular filtration rate, renal LCN-2 and HAVCR-1 mRNA expression levels, and serum creatinine, urea nitrogen and cystatin c levels were also used to evaluate renal function. In addition, the protein levels of LCN-2 and HAVCR-1 in renal, serum and urine were measured. Our results demonstrated that the changes in biomarkers always lagged the real time glomerular filtration rate during the progression and recovery of renal injury. Cystatin-c can reflect renal injury earlier than other markers, but it remains higher in the recovery stage. Perhaps the glomerular filtration rate does not reflect the greater injury caused by vancomycin plus piperacillin.

Abstract Introduction Persons with diabetes are at risk for developing a cardiomyopathy through several pathophysiological mechanisms independent of traditional risk factors for heart failure. Among those with diabetic cardiomyopathy (DbCM), the relationship between natriuretic peptides, cardiac structural abnormalities and functional capacity is largely unknown. Methods In this prespecified subgroup analysis of the Aldose Reductase Inhibition for Stabilization of Exercise Capacity in Heart Failure (ARISE-HF) trial, 685 participants with asymptomatic DbCM underwent baseline echocardiography data, laboratory investigations, and functional assessments. Participants were stratified by N-terminal pro-B type natriuretic peptide (NT-proBNP) quartiles, and correlation with echocardiographic and functional parameters were assessed using Spearman correlation test. Results The median NT-proBNP was 71 (Q1, Q3: 33, 135) ng/L. No association was observed between NT-proBNP concentrations and echocardiographic parameters of either diastolic or systolic dysfunction including global longitudinal strain, left ventricular ejection fraction, left ventricular mass index, left atrial volume index, E/E’, or right ventricular systolic pressure. In contrast, NT-proBNP was significantly correlated with overall Kansas City Cardiomyopathy Questionnaire score (rho = − 0.10; p = 0.007), the Physical Activity Scale in the Elderly (rho = − 0.12; p = 0.004), duration of cardiopulmonary exercise testing (rho = − 0.28; p 95 for females or > 115 for males or E/e’ >13 or left atrial volume index > 34. †Normal ECHO is defined as the absence of these abnormalities. Low NT-proBNP is defined as

Abstract Background Anxiety disorders can cause serious physical and psychological damage, so many anxiety scales have been developed internationally to measure anxiety disorders, but due to the cultural differences and cultural dependence of quality of life between Chinese and Western cultures, it is difficult to reflect the main characteristics of Chinese patients. Therefore, we developed a scale suitable for Chinese patients with anxiety disorders: the Anxiety Disorders Scale of the Quality of Life Instruments for Chronic Diseases (QLICD-AD), hoping to achieve satisfactory QOL assessments for anxiety disorders. Objectives Items from the Anxiety Disorders Scale of the Quality of Life in Chronic Disease Instrument QLICD-AD system were analyzed using CTT and IRT to lay the groundwork for further refinement of the scale to accurately measure anxiety disorders. Methods 120 patients with anxiety disorder were assessed using the QLICD-AD (V2.0). Descriptive statistics, variability method, correlation coefficient method, factor analysis and Cronbach’s coefficient of CTT, and graded response model (GRM) of item response theory were used to analyze the items of the scale. Result CTT analysis showed that the standard deviation of each item was between 0.928 and 1.466; Pearson correlation coefficients of item-to-domain were generally greater than 0.5 and also greater than that of item-to-other domain; the Cronbach ‘s of the total scale was 0.931, α of each domain was between 0.706 and 0.865. IRT analysis showed that the discrimination was between 1.14 and 1.44. The difficulty parameter of all items increased with the increase of grade. But some items (GPH6,GPH8,GPS3,GSO2-GSO4,AD2,AD5) difficulty parameters were less than 4 or greater than 4. The average of information amount was between 0.022 and 0.910. Conclusion Based on CTT and IRT analysis, most items of the QLICD-AD (V2.0) scale have good performance and good differentiation, but a few items still need further revision. Suggests that the QLICD-AD (V2.0) appears to be a valid measure of anxiety disorders. It may effectively improve the diagnosticity of anxiety disorders, but due to the limitations of the current sample, further validation is needed in a broader population extrapolation trial.

Abstract Background Deep learning (DL), a specialized form of machine learning (ML), is valuable for forecasting survival in various diseases. Its clinical applicability in real-world patients with gastric cancer (GC) has yet to be extensively validated. Methods A combined cohort of 11,414 GC patients from the Surveillance, Epidemiology and End Results (SEER) database and 2,846 patients from a Chinese dataset were utilized. The internal validation of different algorithms, including DL model, traditional ML models, and American Joint Committee on Cancer (AJCC) stage model, was conducted by training and testing sets on the SEER database, followed by external validation on the Chinese dataset. The performance of the algorithms was assessed using the area under the receiver operating characteristic curve, decision curve, and calibration curve. Results DL model demonstrated superior performance in terms of the area under the curve (AUC) at 1, 3, and, 5 years post-surgery across both datasets, surpassing other ML models and AJCC stage model, with AUCs of 0.77, 0.80, and 0.82 in the SEER dataset and 0.77, 0.76, and 0.75 in the Chinese dataset, respectively. Furthermore, decision curve analysis revealed that the DL model yielded greater net gains at 3 years than other ML models and AJCC stage model, and calibration plots at 3 years indicated a favorable level of consistency between the ML and actual observations during external validation. Conclusions DL-based model was established to accurately predict the survival rate of postoperative patients with GC.

Abstract Background Diabetic cardiomyopathy (DbCM) is a form of Stage B heart failure (HF) at high risk for progression to overt disease. Using baseline characteristics of study participants from the Aldose Reductase Inhibition for Stabilization of Exercise Capacity in Heart Failure (ARISE-HF) Trial we sought to characterize clinical characteristics of individuals with findings consistent with DbCM. Methods Among study participants meeting inclusion criteria, clinical characteristics, laboratory testing, imaging, Kansas City Cardiomyopathy Questionnaire (KCCQ), Physical Activity Scale of the Elderly (PASE) and cardiopulmonary exercise testing (CPET) results were tabulated. Cluster phenogroups were identified. Results Among 691 study participants (mean age 67.4 years; 50% were female), mean duration of type 2 diabetes mellitus (T2DM) was 14.5 years. The median (Q1, Q3) N-terminal pro-B type natriuretic peptide and high sensitivity cardiac troponin T were 71 (35, 135) ng/L and 9 [6, 12] ng/L. The most common echocardiographic abnormalities were reduced global longitudinal strain in 25.3% and impaired diastolic relaxation in 17.7%. Despite rather well-preserved KCCQ scores the average PASE score was markedly impaired at 155 accompanied by an average maximal oxygen consumption of 15.7 mL/Kg/minute on CPET. In K-means clustering, 4 phenogroups were identified including a higher-risk group with more advanced age, greater elevation of cardiac biomarkers, and more prevalent evidence for diastolic dysfunction and left ventricular hypertrophy. Conclusions Baseline data from the ARISE-HF Trial provide clinical characterization of individuals with T2DM and features of stage B HF, and may help clarify the diagnosis of DbCM. Trial Registration ARISE-HF, NCT04083339.

Abstract Objective The present study is aimed to develop and validate a quality of life scale for systemic lupus erythematosus (SLE) patients with Chinese cultural background, QLICD-SLE (V2.0). Methods The QLICD-SLE (V2.0) was developed using a systematic approach that involved focus groups, nominal discussions, and pilot testing. A total of 428 SLE patients participated in the scale's assessment. Validity was examined through qualitative analysis, item domain correlation, multidimensional scaling, and factor analysis. Reliability was assessed using Pearson's correlation and Cronbach's alpha coefficients. To evaluate responsiveness, paired T-tests were conducted to compare pre- and post-treatment measurements with the standardised response mean (SRM) being calculated. Results Correlation and factor analyses demonstrated strong construct validity. When using SF-36 as criteria, the correlation between various domains of QLICD-SLE and SF-36 ranged from 0.55 to 0.70. Test–retest correlation coefficients exceeded 0.71, and Cronbach’s alpha coefficients for both measurements in each domain were greater than or equal to 0.75. T-test results showed that both the overall score and most facet scores within each domain showed statistically significant changes after treatment (P

Abstract Background The insulin-like growth factors (IGF) play a crucial role in regulating cellular proliferation, apoptosis, and key metabolic pathways. The ratio of IGF-1 to IGF binding protein-3 (IGFBP-3) is an important factor in determining IGF-1 bioactivity. We sought to investigate the association of IGF-1 and IGFBP-3 with cardio-renal outcomes among persons with type 2 diabetes. Methods Samples were available from 2627 individuals with type 2 diabetes and chronic kidney disease that were randomized to receive canagliflozin or placebo and were followed up for incident cardio-renal events. Primary outcome was defined as a composite of end-stage kidney disease, doubling of the serum creatinine level, or renal/cardiovascular death. IGF-1 and IGFBP-3 were measured at baseline, Year-1 and Year-3. Elevated IGF-1 level was defined according to age-specific cutoffs. Cox proportional hazard regression was used to investigate the association between IGF-1 level, IGFBP-3, and the ratio of IGF-1/IGFBP-3 with clinical outcomes. Results Elevated IGF-1 was associated with lower glomerular filtration rate at baseline. Treatment with canagliflozin did not significantly change IGF-1 and IGFBP-3 concentrations by 3 years (p-value > 0.05). In multivariable models, elevated IGF-1 (above vs below age-specific cutoffs) was associated with the primary composite outcome (incidence rate:17.8% vs. 12.7% with a hazard ratio [HR]: 1.52; 95% confidence interval CI 1.09–2.13;P: 0.01), renal composite outcome (HR: 1.65; 95% CI 1.14–2.41; P: 0.01), and all-cause mortality (HR: 1.52; 95% CI 1.00–2.32; P; 0.05). Elevations in log IGFBP-3 did not associate with any clinical outcomes. Increase in log IGF-1/IGFBP-3 ratio was also associated with a higher risk of the primary composite outcome (HR per unit increase: 1.57; 95% CI 1.09–2.26; P; 0.01). Conclusions These results further suggest potential importance of IGF biology in the risk for cardio-renal outcomes in type 2 diabetes. SGLT2 inhibition has no impact on the biology of IGF despite its significant influence on outcomes. Trial registration: CREDENCE; ClinicalTrials.gov Identifier: NCT02065791.

Abstract Background Although mesenchymal stem cells (MSCs) have been effective in tendinopathy, the mechanisms by which MSCs promote tendon healing have not been fully elucidated. In this study, we tested the hypothesis that MSCs transfer mitochondria to injured tenocytes in vitro and in vivo to protect against Achilles tendinopathy (AT). Methods Bone marrow MSCs and H2O2-injured tenocytes were co-cultured, and mitochondrial transfer was visualized by MitoTracker dye staining. Mitochondrial function, including mitochondrial membrane potential, oxygen consumption rate, and adenosine triphosphate content, was quantified in sorted tenocytes. Tenocyte proliferation, apoptosis, oxidative stress, and inflammation were analyzed. Furthermore, a collagenase type I-induced rat AT model was used to detect mitochondrial transfer in tissues and evaluate Achilles tendon healing. Results MSCs successfully donated healthy mitochondria to in vitro and in vivo damaged tenocytes. Interestingly, mitochondrial transfer was almost completely blocked by co-treatment with cytochalasin B. Transfer of MSC-derived mitochondria decreased apoptosis, promoted proliferation, and restored mitochondrial function in H2O2-induced tenocytes. A decrease in reactive oxygen species and pro-inflammatory cytokine levels (interleukin-6 and -1β) was observed. In vivo, mitochondrial transfer from MSCs improved the expression of tendon-specific markers (scleraxis, tenascin C, and tenomodulin) and decreased the infiltration of inflammatory cells into the tendon. In addition, the fibers of the tendon tissue were neatly arranged and the structure of the tendon was remodeled. Inhibition of mitochondrial transfer by cytochalasin B abrogated the therapeutic efficacy of MSCs in tenocytes and tendon tissues. Conclusions MSCs rescued distressed tenocytes from apoptosis by transferring mitochondria. This provides evidence that mitochondrial transfer is one mechanism by which MSCs exert their therapeutic effects on damaged tenocytes.

Abstract Exposure to fine particulate matter (PM2.5) is linked to lung cancer incidence and mortality. However, the impact of PM2.5 exposure on lung cancer patients after lobectomy, which remains the primary treatment for early-stage lung cancer, is unknown. Therefore, we investigated the correlation between PM2.5 exposure and the survival of lung cancer patients after lobectomy. This study included 3,327 patients with lung cancer who underwent lobectomy procedures. We converted residential addresses into coordinates and estimated individual patients' daily PM2.5 and O3 exposure levels. A Cox multivariate regression model was used to analyze the specific monthly association between PM2.5 exposure and lung cancer survival. Every 10 μg/m3 increase in monthly PM2.5 concentration in the first and second months after lobectomy increased the risk of death (hazard ratio [HR]: 1.043, 95% confidence interval [CI]: 1.019–1.067 and HR: 1.036, 95% CI: 1.013–1.060, respectively). Non-smokers, younger patients, and patients with longer hospitalization durations had worse survival rates when exposed to greater concentrations of PM2.5. High postoperative PM2.5 exposure immediately after lobectomy reduced the survival of patients with lung cancer. Patients living in areas with high PM2.5 should be offered the opportunity to transfer to areas with better air quality after undergoing lobectomies, to prolong their survival times.

Abstract Background Breast parenchymal texture features, including grayscale variation (V), capture the patterns of texture variation on a mammogram and are associated with breast cancer risk, independent of mammographic density (MD). However, our knowledge on the genetic basis of these texture features is limited. Methods We conducted a genome-wide association study of V in 7040 European-ancestry women. V assessments were generated from digitized film mammograms. We used linear regression to test the single-nucleotide polymorphism (SNP)-phenotype associations adjusting for age, body mass index (BMI), MD phenotypes, and the top four genetic principal components. We further calculated genetic correlations and performed SNP-set tests of V with MD, breast cancer risk, and other breast cancer risk factors. Results We identified three genome-wide significant loci associated with V: rs138141444 (6q24.1) in ECT2L, rs79670367 (8q24.22) in LINC01591, and rs113174754 (12q22) near PGAM1P5. 6q24.1 and 8q24.22 have not previously been associated with MD phenotypes or breast cancer risk, while 12q22 is a known locus for both MD and breast cancer risk. Among known MD and breast cancer risk SNPs, we identified four variants that were associated with V at the Bonferroni-corrected thresholds accounting for the number of SNPs tested: rs335189 (5q23.2) in PRDM6, rs13256025 (8p21.2) in EBF2, rs11836164 (12p12.1) near SSPN, and rs17817449 (16q12.2) in FTO. We observed significant genetic correlations between V and mammographic dense area (r g = 0.79, P = 5.91 × 10−5), percent density (r g = 0.73, P = 1.00 × 10−4), and adult BMI (r g = − 0.36, P = 3.88 × 10−7). Additional significant relationships were observed for non-dense area (z = − 4.14, P = 3.42 × 10−5), estrogen receptor-positive breast cancer (z = 3.41, P = 6.41 × 10−4), and childhood body fatness (z = − 4.91, P = 9.05 × 10−7) from the SNP-set tests. Conclusions These findings provide new insights into the genetic basis of mammographic texture variation and their associations with MD, breast cancer risk, and other breast cancer risk factors.

Abstract Background A short instrument would enhance the viability of a study. Therefore, we aimed to shorten the specific module (SPD-10) of the Quality of Life Instrument for Chronic Diseases - Chronic Renal Failure (QLICD-CRF) for assessing the quality of life of patients with chronic renal failure. Methods The 10-item SPD-10 was self-administered to 164 patients with chronic renal failure. A shortened form was first obtained by a tandem use of the classical test theory (CTT), the generalizability theory (GT), and the item response theory (IRT). In addition, we also shortened the SPD-10 by the Optimal Test Assembly (OTA). Results Both the tandem use of GT, CTT and IRT, and the OTA derived the same 7-item shortened version (SPD-7). It included items CRF1, CRF2, CRF3, CRF4, CRF6, CRF8, and CRF9 of the SPD-10. The SPD-7 had a Cronbach alpha of 0.78. The correlation coefficients of its total and factor scores with those of the SPD-10 were 0.96 and 0.98, respectively. Confirmatory factor analysis confirmed the unidimensional structure of the SPD-7, with the comparative fit index=0.96, the Tucker-Lewis index=0.94, and the root mean square error of approximation=0.09. Conclusion The short-form SPD-7 is reliable and valid for assessing the impact of clinical symptoms and side effects on the quality of life of patients with chronic renal failure. It is an efficient option without compromising the measurement performance of the SPD-10.

Abstract Background Drug abuse has many negative effects not only on individuals but also on society. Nowadays, researchers pay a lot of attention to quality of life of drug addicts. However, there are few scales available to measure quality of life of drug addicts. The scale QLICD-DA (quality of life instrument for chronic diseases-drug addition) developed by modular approach could be used to measure quality of life of drug addicts with good validity, reliability and sensitivity. Objective This study is aimed to understand the quality of life status and influencing factors in drug addicts by suitable sensitively scale, with the hypothesis of the quality of life in drug addicts being different from that of other peoples and possibly being influenced by many factors. Methods By cluster random sampling method, 192 drug addicts at Kunming compulsory drug rehabilitation center were recruited to take part in the investigation. All participants completed the general information questionnaire and the scale QLICD-DA. We used a t-test to compare the scores of the quality of life of the participants with the norm (QOL scores from 1953 patients of 10 chronic diseases). A stepwise regression method was applied to explore the influencing factors of the quality of life in drug addicts. Results 192 participants ranged in age from 19 to 59 with an average age of 34.86. Most of them were male (70.3%), high school education level (67.7%) and of Han nationality (82.8%). The quality of life of drug addicts was lower than the norm in the physical domain, psychological domain, social domain, and general module, and the differences were statistically significant (p

Abstract Background The mutational profile of cancer reflects the activity of the mutagenic processes which have been operative throughout the lineage of the cancer cell. These processes leave characteristic profiles of somatic mutations called mutational signatures. Mutational signatures, including single-base substitution (SBS) signatures, may reflect the effects of exogenous or endogenous exposures. Methods We used polygenic risk scores (PRS) to summarize common germline variation associated with cancer risk and other cancer-related traits and examined the association between somatic mutational profiles and germline PRS in 12 cancer types from The Cancer Genome Atlas. Somatic mutational profiles were constructed from whole-exome sequencing data of primary tumors. PRS were calculated for the 12 selected cancer types and 9 non-cancer traits, including cancer risk determinants, hormonal factors, and immune-mediated inflammatory diseases, using germline genetic data and published summary statistics from genome-wide association studies. Results We found 17 statistically significant associations between somatic mutational profiles and germline PRS after Bonferroni correction (p < 3.15 × 10−5), including positive associations between germline inflammatory bowel disease PRS and number of somatic mutations attributed to signature SBS1 in prostate cancer and APOBEC-related signatures in breast cancer. Positive associations were also found between age at menarche PRS and mutation counts of SBS1 in overall and estrogen receptor-positive breast cancer. Consistent with prior studies that found an inverse association between the pubertal development PRS and risk of prostate cancer, likely reflecting hormone-related mechanisms, we found an inverse association between age at menarche PRS and mutation counts of SBS1 in prostate cancer. Inverse associations were also found between several cancer PRS and tumor mutation counts. Conclusions Our analysis suggests that there are robust associations between tumor somatic mutational profiles and germline PRS. These may reflect the mechanisms through hormone regulation and immune responses that contribute to cancer etiology and drive cancer progression.

Abstract Background Triple-negative breast cancer (TNBC) is highly metastatic and lethal. Due to a lack of druggable targets for this disease, there are no effective therapies in the clinic. Methods We used TNBC cells and xenografted mice as models to explore triptonide-mediated inhibition of TNBC metastasis and tumor growth. Colony formation assay was used to quantify the tumorigenesis of TNBC cells. Wound-healing and cell trans-well assays were utilized to measure cell migration and invasion. Tube formation assay was applied to access tumor cell-mediated vasculogenic mimicry. Western blot, quantitative-PCR, immunofluorescence imaging, and immunohistochemical staining were used to measure the expression levels of various tumorigenic genes in TNBC cells. Results Here, we showed that triptonide, a small molecule from the traditional Chinese medicinal herb Tripterygium wilfordii Hook F, potently inhibited TNBC cell migration, invasion, and vasculogenic mimicry, and effectively suppressed TNBC tumor growth and lung metastasis in xenografted mice with no observable toxicity. Molecular mechanistic studies revealed that triptonide strongly triggered the degradation of master epithelial-mesenchymal transition (EMT)-inducing protein Twist1 through the lysosomal system and reduced Notch1 expression and NF-κB phosphorylation, which consequently diminished the expression of pro-metastatic and angiogenic genes N-cadherin, VE-cadherin, and vascular endothelial cell growth factor receptor 2 (VEGFR2). Conclusions Triptonide effectively suppressed TNBC cell tumorigenesis, vasculogenic mimicry, and strongly inhibited the metastasis of TNBC via degradation of Twist1 and Notch1 oncoproteins, downregulation of metastatic and angiogenic gene expression, and reduction of NF-κB signaling pathway. Our findings provide a new strategy for treating highly lethal TNBC and offer a potential new drug candidate for combatting this aggressive disease.

Abstract Background Accidental drowning of children under five is a serious problem in China. The present study analyzed data on environmental and sociodemographic factors and on primary caregivers of drowned children to understand factors that may contribute to this problem. Methods The present study collected information on 563 cases of drowning in children under five from October 1, 2015, to September 30, 2016, in 334 sampling districts in China. Primary caregivers were interviewed individually using the Drowning Mortality among Children under 5 Questionnaire. Results Most drowned children under 5 years old were boys, and 71.6% lived within 100 m of a body of water. The drownings primarily occurred in ponds, canals, rivers, and wells, and over 90% of these water bodies had no safety measures. There were 28.1% of primary caregivers who did not provide full-time care for the children, and 83.1% of them had no knowledge of first aid skills for drowning. Conclusion Encouraging kindergarten enrollment and providing safety education for children may reduce drowning in children under 5 years of age. Public water body protection measures should be strengthened to prevent children from drowning. Encouraging primary caregivers to care full-time for the children and learning first aid skills for drowning may also help reduce fatalities.

Abstract Background To introduce a model of community health service organization (as implemented in urban areas) to less developed rural areas in China and evaluate the impact of this model on health care utilization. Methods The intervention involved developing leadership at county level, training rural health practitioners, providing clinical management guidelines and standards, encouraging clinic improvements and providing access to subsidies for public health work. We chose 7 townships and 49 administrative villages in Chongyi County as the intervention sites; 3 townships and 9 administrative villages in Luxi County as the comparison sites. Officers from county health bureaus and postgraduates from School of Public Health, Nanchang University visited each township hospital and village clinic in field together and made observations and interviewed clinic staff. Results There was little change in health facilities or workforce in the two areas. However, there was an increase in the use of public health services at township and village level in the intervention sites in Chongyi. In these, the proportion of clinics which had developed a child health (under the age of 3) management system, maternal postpartum visit and chronic disease management increased from 53%, 51% and 47% to 78%, 73%, and 71% respectively. There was no significant change in the comparison sites. Conclusions The trial demonstrated that it was feasible to implement a model of community health service delivery that was adapted to depressed rural areas because it required little organizational change, additional funding or personnel. The model had a positive impact on the provision of public health programs, a finding which has implications for efforts to improve access to primary health care in rural China.