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Purpose: This phase I trial is to determine the recommended dose of the TAS-102, irinotecan plus bevacizumab regimen and assess its safety and efficacy in patients with metastatic colorectal cancer refractory to fluoropyrimidine and oxaliplatin treatment. Methods: A 3 + 3 designed dose escalation was performed. Patients were administered TAS-102 (30–35 mg/m2 twice daily on days 1–5) and irinotecan (150–165 mg/m2 on day 1) combined with a fixed dose of bevacizumab (5 mg/kg on day 1) every two weeks. The primary endpoint was the determination of the recommended phase II dose. Results: Eighteen patients were enrolled: 6 at the Level 1 (TAS-102 30 mg/m2 twice daily, irinotecan 150 mg/m2 plus bevacizumab 5 mg/kg), six at the Level 2 (TAS-102 35 mg/m2 twice daily, irinotecan 150 mg/m2 plus bevacizumab 5 mg/kg), and six at the Level 3 (TAS-102 30 mg/m2 twice daily, irinotecan 165 mg/m2 plus bevacizumab 5 mg/kg). Five dose-limiting toxicities occurred: one observed at Level 1 (thrombocytopenia), two at Level 2 (neutropenia and diarrhea), and two at Level 3 (fatigue and neutropenia). The RP2D was established as TAS-102 30 mg/m2 twice daily and irinotecan 150 mg/m2 plus bevacizumab 5 mg/kg. The most frequent grade 3/4 treatment-related adverse events were neutropenia (33.3%), diarrhea (16.7%), and thrombocytopenia (11.1%). No treatment-related death occurred. Two patients (11.1%) experienced partial responses and 14 (77.8%) had stable disease. Conclusion: The regimen of TAS-102, irinotecan, and bevacizumab is tolerable with antitumor activity for metastatic colorectal cancer patients refractory to first-line fluoropyrimidines and oxaliplatin treatment. [ABSTRACT FROM AUTHOR]

This study examined the psychometric properties of the Chinese version of the Social-Emotional Assessment Measure (SEAM) (33–66 months), which is designed to assess social-emotional difficulties and behavior disorders in young children. In this case, the SEAM was translated and back-translated. The sample included 2477 preschoolers (1256 boys; M age = 57.57 months, SD = 10.93) residing in Shanghai, China. In summary, the results presented a 10-factor model that showed a good fit for the SEAM (33–66 months). Ultimately, the analyses demonstrated adequate internal consistency, reliability, and convergent validity. These findings indicate that the SEAM (33–36 months) is appropriate for use in Chinese preschool populations. [ABSTRACT FROM AUTHOR]

Introduction: In 2015, the term 'intrinsic capacity' (IC) was proposed by the World Health Organisation to promote healthy aging. However, the factors associated with IC are still discrepant and uncertain. Aim: We aim to synthesise the factors connected with IC. Methods: This scoping review followed the five‐stage framework of Arksey and O'Malley and was reported using PRISMA‐ScR guidelines. Results: In all, 29 articles were included. IC of older adults is associated with demographic characteristics, socioeconomic factors, disease conditions, behavioural factors, and biomarkers. Age, sex, marital status, occupation status, education, income/wealth, chronic diseases, hypertension, diabetes, disability, smoking status, alcohol consumption, and physical activity were emerged as important factors related to the IC of older adults. Conclusions: This review shows that IC is related to multiple factors. Understanding these factors can provide the healthcare personnel with the theoretical basis for intervening and managing IC in older adults. Relevance to Clinical Practice: The influencing factors identified in the review help to guide older adults to maintain their own intrinsic capacity, thereby promoting their health and well‐being. The modifiable factors also provide evidence for healthcare personnel to develop targeted intervention strategies to delay IC decline. No Patient or Public Contribution: As this is a scoping review, no patient or public contributions are required. [ABSTRACT FROM AUTHOR]

Background: The surgical approach for patients with Siewert type II AEG remains controversial. Several studies have described a new laparoscopic radical resection approach of Siewert type II AEG through the left diaphragm. However, the technical safety and feasibility of the new surgical approach compared with the transhiatal approach have not yet been tested. Study design: We retrospectively reviewed patients with AEG who underwent TSLG and LTH operations in the Guangdong Provincial Hospital of Chinese Medicine between January 2017 and April 2021. Histologically confirmed AEG and D2 lymphadenectomy with curative R0 patients were included, and patients with Siewert I/III AEG or distant metastasis were excluded. Blood loss, the amount of harvested lymph node, and complications related to surgery were evaluated. Results: A total of 99 patients with Siewert type II AEG were analyzed, 44 in the TSLG group and 55 in the LTH group. There was no difference in clinicopathological features between the two groups. The more harvested lymph node (23.33 ± 11.41 vs. 32.18 ± 12.85, p < 0.01), lower mediastinal lymph node (1.07 ± 2.08 vs. 3.25 ± 3.31, p < 0.01), and longer proximal margin length (3.08 ± 1.19 vs. 4.47 ± 0.95 cm, p < 0.01) were observed in the TSLG group. The rate of cure (R0 gastrectomy) in the TSLG group was higher than that in the LTH group (100% vs. 89.09%, p = 0.03). Conclusion: The TSLG approach is associated with improved surgical views, simplified lymphatic dissection in the inferior mediastinum, and more reliable margins. TSLG surgery may be an effective addition to LTH surgery, particularly when lower mediastinal lymph node metastases are suspected. [ABSTRACT FROM AUTHOR]

Background: Several factors can influence the risk of dental caries, among which dietary factors have a significance impact on the occurrence of dental caries. The limitation of current studies is that they only focus on the influence of individual foods on the risk of dental caries. This study use cluster analysis to examine the relationship between dietary patterns and dental caries experience among adolescents aged 12–15. Methods: Based on data from the first oral epidemic survey in Shanxi Province, a cross-sectional study was conducted among 11,351 adolescents aged 12–15 in Shanxi Province through oral examination and questionnaires. The questionnaire included the intake frequency of seven types of food. Descriptive statistics, cluster analysis, and multinomial logistic regression were used to analyze the association between dietary patterns and dental caries experience. Results: The prevalence rate of caries was 44.57% and the mean DMFT score was 0.98 ± 1.49 in adolescents aged 12–15 in Shanxi Province. The caries rate was higher in females than males (X2 = 103.59, P < 0.001). Adolescents who grow up in one-child families have a lower caries risk than those who grow up in families with more than one child (OR:0.91; 95%CI:0.84–0.97). The dietary patterns of adolescents aged 12–15 can be divided into eight types, among which refreshments-rich diet (OR:1.47; 95%CI,1.22–1.77) can increase the risk of caries, while the coarse-grains-rich dietery pattern (OR:0.90; 95%CI, 0.79–0.97) has a lower caries risk. Conclusions: Social determinants of health such as sex, family size and dietary patterns influence the risk of dental caries. Certain dietary patterns could increase or decrease the risk of caries. The government, school canteens and news media should take dietary pattern factors seriously. [ABSTRACT FROM AUTHOR]

Objective. To compare eye-related quality of life between Chinese children wearing orthokeratology (OK) contact lenses and single-vision spectacles (SVS) using the Pediatric Eye Questionnaire (PedEyeQ) and to evaluate the impact of different myopia correction methods on children and their parents. Methods. Children aged 12–17 years and their parents/legal guardians were recruited. The children's myopia ranged from −0.50 to −5.00 diopters (D), and their astigmatism was <1.50 D. They had all been wearing OK contact lenses or SVS for at least 12 months. The children completed the Child PedEyeQ. One of their parents (or a legal guardian) completed the Proxy PedEyeQ and the Parent PedEyeQ. Rasch-calibrated PedEyeQ scores were calculated for each domain and were converted to a scale from 0 to 100 for statistical analysis. Results. A total of 50 children wearing OK contact lenses, 43 children wearing SVS, and their parents/legal guardians completed the questionnaires. The scores of all Child, Proxy, and Parent PedEyeQ domains in the OK contact lens group were higher than those in the SVS group (all P < 0.05). In the mild and moderate myopia subgroups, the Child, Proxy, and Parent PedEyeQ scores in the mild myopia OK contact lens subgroup were higher than those in the mild myopia SVS group (all P < 0.05) except functional vision and bothered by eyes/vision domains for the proxy PedEyeQ. Similarly, the Child, Proxy, and Parent PedEyeQ scores in the moderate myopia OK contact lens subgroup were higher than those in the moderate myopia SVS subgroup (all P < 0.05) except impact on parent and family domain for the parent PedEyeQ. In the subgroup analysis of glasses type, no significant score difference of any Child, Proxy, and Parent PedEyeQ domain was detected between mild and moderate myopia in either the OK contact lens group or the SVS group (all P > 0.05). Conclusion. Compared with children wearing SVS, children wearing OK contact lenses have better functional vision and eye-related quality of life. Moreover, OK contact lens has a better correction effect, higher acceptance rates, and less impact on parents and families than SVS. [ABSTRACT FROM AUTHOR]

• This is the first meta-analysis to explore and summarize the predictive value of intrinsic capacity decline on functional disability among the elderly. • The findings showed intrinsic capacity decline could significantly predict functional disability in the elderly. • We conducted a systematic review that impairments in specific domains of intrinsic capacity were associated with an increased risk of functional disability. To examine the predictive value of intrinsic capacity decline on functional disability among the elderly. Meta-analysis. PubMed, EMBASE, Web of Science, The Cochrane Library, Wanfang Database, China Knowledge Resource Integrated Database (CNKI), Weipu Database (VIP), and Chinese Biomedical Database (CBM) were searched for relevant studies published from the inception until June 1, 2024. Stata 17.0 software was used to perform the meta-analysis. The methodological quality was evaluated using the Newcastle Ottawa Scale. The overall quality of evidence used GRADE guidelines to assess. A study protocol was registered in PROSPERO (CRD42023475461). The meta-analysis included 8 cohort studies including 9744 elderly people. Functional disability including ADL disability (n = 6) and IADL disability (n = 7). The results showed that intrinsic capacity decline could predict ADL disability (HR = 1.08, 95 %CI 1.04–1.12; I 2 = 98.2 %, P < 0.001) and IADL disability (HR = 1.11, 95 %CI 1.05–1.17; I 2 = 96.4 %, P < 0.001). The overall risk of bias was low. And the grade of evidence that assessed by GRADE guidelines was rated as moderate. Intrinsic capacity decline is a predictor of functional disability in the elderly. Therefore, screening intrinsic capacity decline has important clinical implications for early identifying the risk of functional disability, which contributes to providing individualized interventions ahead of potential functional disability for the elderly, thereby preventing functional disability, improving the quality of life and promoting healthy aging. [ABSTRACT FROM AUTHOR]

The objective of this study was to estimate the joint effects of cognitive impairment and depressive symptoms on health‐related quality of life (HRQoL) and to explore the mediating role of disability among Chinese community‐dwelling older adults. A cross‐sectional study was conducted with 2525 community‐dwelling older adults aged ≥60 years and living in Shanghai, China in 2019. Participants were divided into four groups: (1) non‐depressed without dementia, (2) non‐depressed with probable MCI, (3) depressed without dementia and (4) depressed with probable mild cognitive impairment (MCI). HRQoL was assessed using the 36‐Item Short‐Form Health Survey. Cognitive impairment and depressive symptoms were evaluated with the AD8 and the Geriatric Depression Scale respectively. Activities of daily living (ADL) and instrumental activities of daily living (IADL) disability and other sociodemographic variables were also assessed. The results of this study showed that controlling for sociodemographic characteristics, significant differences in a physical component score (PCS) and a mental component score (MCS) of HRQoL were found across the four groups. Compared to those who were non‐depressed without dementia, older adults who were depressed with probable MCI reported the lowest level of PCS and MCS, followed by older adults who were depressed without dementia. Both ADL and IADL disabilities played mediating roles in the relationship between cognitive impairment and depressive symptoms and PCS. Based on this study, we suggest that the early detection and adequate management of depressive symptoms and cognitive status—as well as efforts to improve individuals' ability to manage their ADLs and IADLs—may help to maintain or improve their HRQoL. [ABSTRACT FROM AUTHOR]

Background: The purpose of this study was to survey the associations of six single nucleotide polymorphisms (SNPs) in the TMOD1 and PTCSC2 genes with thyroid carcinoma (TC). Method: Peripheral blood samples were obtained from 510 patients with TC and 509 normal controls. Six SNPs were genotyped by the Agena MassARRAY platform. Logistic regression was used to evaluate the association between SNPs and TC susceptibility by calculating odds ratios (ORs) and 95% confidence intervals (CIs). SNP-SNP interactions were analyzed by multifactor dimensionality reduction (MDR). Results: Our study showed that rs925489 (OR = 1.45, p = 0.011) and rs965513 (OR = 1.40, p = 0.021) were significantly associated with an increased risk of TC. Rs10982622 decreased TC risk (OR = 0.74, p = 0.025). Further stratification analysis showed that rs10982622 reduced the susceptibility to TC in patients aged ≤ 45 years (OR = 0.69, p = 0.019) and in females (OR = 0.61, p = 0.014). Rs925489 increased TC risk in people aged > 45 years (OR = 1.54, p = 0.044) and in males (OR = 2.34, p = 0.003). In addition, rs965513 was related to an increased risk of TC in males (OR = 2.14, p = 0.007). Additionally, haplotypes in the block (rs925489|rs965513) significantly increased TC risk (p < 0.05). The best predictive model for TC was the combination of rs1052270, rs10982622, rs1475545, rs16924016, and rs925489. Conclusion: TMOD1 and PTCSC2 polymorphisms were separately correlated with a remarkable decrease and increase in TC risk based on the analysis. [ABSTRACT FROM AUTHOR]

Purpose. To explore the effect of Shenkang injection (SKI) combined with Jinshuibao for early diabetic nephropathy (DN) and its effect on the coagulation fibrinolysis system and urinary protein. Methods. 136 patients with early DN admitted to our hospital from March 2018 to October 2019 were divided into the observation group (n = 68) and the control group (n = 68) randomly. On the basis of the conventional treatment, the control group was treated with SKI, and the observation group was treated with SKI and Jinshuibao. Two weeks later, the therapeutic effects of the 2 groups were compared. The prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin time (TT), fibrinogen (FIB), tissue plasminogen activator (t-PA), plasminogen activator inhibitor-1 (PAI-1), and D-dimer (D-D) were observed and compared before and after the treatment. 24 hour urine total protein (24 h-UTP), urine albumin excretion rate (UAER), and urine β2 microglobulin (β2-MG) were measured and compared before and after the treatment. Adverse reactions in the two groups were recorded during the treatment. Results. The effective rate of the observation group after treatment was 92.65% higher than the control group 79.41%. the difference was statistically significant (P < 0.05). The levels of PT, APTT, TT, FIB, PAI-1, and D-D in the two groups after treatment were lower, and t-PA levels after treatment were higher than those before, and all of the above indicators were significantly changed in the observation group than in the control group. The difference was statistically significant (P < 0.05). The 24 h-UTP, UAER, and β2-MG in the two groups after treatment were lower than those before, and all of the above indicators were significantly changed in the observation group than in the control group. The difference was statistically significant (P < 0.05). There was no statistically significant difference during the treatment for 2 groups in terms of adverse reactions. The difference was statistically significant (P > 0.05). Conclusion. SKI combined with Jinshuibao has a significant effect in the treatment of early DN, which can reduce the risk of hyperfunction of coagulation and fibrinolysis system, further reduce the content of urine protein, and delay the process of DN. [ABSTRACT FROM AUTHOR]

Background: The aim of present study was to screen the novel and promising targets of curcumin in hepatocellular carcinoma diagnosis and chemotherapy. Methods: Potential targets of curcumin were screened from SwissTargetPrediction, ParmMapper and drugbank databases. Potential aberrant genes of hepatocellular carcinoma were screened from Genecards databases. Fifty paired hepatocellular carcinoma patients' gene expression profiles from the GEO database were used to test potential targets of curcumin. Besides, GO analysis, KEGG pathway enrichment analysis and PPI network construction were used to explore the underlying mechanism of candidate hub genes. ROC analysis and Kaplan-Meier analysis were used to evaluate the diagnostic and prognostic value of candidate hub genes, respectively. Real-time PCR was used to verify the results of bioinformatics analysis. Results: Bioinformatics analysis results suggested that AURKA, CDK1, CCNB1, TOP2A, CYP2B6, CYP2C9, and CYP3A4 genes served as candidate hub genes. AURKA, CDK1, CCNB1 and TOP2A were significantly upregulated and correlated with poor prognosis in hepatocellular carcinoma, AUC values of which were 95.7, 96.9, 98.1 and 96.1% respectively. There was not significant correlation between the expression of CYP2B6 and prognosis of hepatocellular carcinoma, while CYP2C9 and CYP3A4 genes were significantly downregulated and correlated with poor prognosis in hepatocellular carcinoma. AUC values of CYP2B6, CYP2C9, and CYP3A4 were 96.0, 97.0 and 88.0% respectively. In vitro, we further confirmed that curcumin significantly downregulated the expression of AURKA, CDK1, and TOP2A genes, while significantly upregulated the expression of CYP2B6, CYP2C9, and CYP3A4 genes. Conclusions: Our results provided a novel panel of AURKA, CDK1, TOP2A, CYP2C9, and CYP3A4 candidate genes for curcumin related chemotherapy of hepatocellular carcinoma. [ABSTRACT FROM AUTHOR]

Background: Depression is common in patients with multimorbidity, but little is known about the relationship between depression and multimorbidity. The purpose of our research was to investigate multimorbidity patterns and their association with depression in a sample of older people covered by long‐term care insurance in Shanghai, China. Method: This was a population‐based cross‐sectional study, with 1871 participants aged ≥60 years old who are covered by Shanghai long‐term care insurance. Multimorbidity was defined as the presence of two or more chronic diseases at the same time. We collected information on chronic conditions using a self‐reported medical history, and we used the 30‐item Geriatric Depression Scale (GDS‐30) to evaluate depressive symptoms. Patterns of multimorbidity were identified with exploratory factor analysis, using oblimin rotation. Logistic regression was used to estimate the relationship between multimorbidity patterns and depressive symptoms. Results: Among the participants, the prevalence of multimorbidity was 64.7%, and the prevalence of depression was 64.6%. Hypertension, cardiovascular disease, cerebrovascular disease (CVD), and cataracts showed strong associations with depression when co‐occurring with other conditions. Three patterns of multimorbidity were identified: a musculoskeletal pattern, cardiometabolic pattern, and degenerative disease pattern. Among these, the cardiometabolic (adjusted odds ratio (AOR) 1.223; 95% confidence interval (CI) 1.102, 1.357) and degenerative disease (AOR 1.185; 95% CI 1.071, 1.311) patterns were associated with a higher risk of depressive symptoms. Conclusion: Two of three multimorbidity patterns were found to be associated with depression. Physical and psychological dimensions require greater attention in the care of older adults who are covered by long‐term care insurance. [ABSTRACT FROM AUTHOR]

Background: The aim of this study is to explore the spatial heterogeneity of the retention of PFS in children aged 7–9 years in Shanxi Province, North China and investigate the risk factors associated with PFS retention. Methods: In this study, 937 children aged 7–9 years from Shanxi Province, China were randomly selected, all of whom had at least one first permanent tooth sealed with PFS in 2016. The children were surveyed after 12 months (in 2017) and 24 months (in 2018). The Geo-detector model was used to explore the spatial heterogeneity of the retention rate of PFS and analyze the influence and interactions of the ecological factors on PFS. Results: 3299 teeth from 937 children were analyzed. The PFS full retention rates after 12 months (in 2017) and 24 months (in 2018) were 81.6% and 75.1%, respectively. The incidence of caries of the first molar was 2.1% after 12 months and 5.4% after 24 months. The spatial heterogeneity of the PFS retention rate after 24 months was significant, which was shown as the retention rate of PFS increased from north to south after 24 months. Remarkably, the natural environmental factors exerted greater influence than the socioeconomic and medical resources factors after 12 months, where the interaction of fluorine in water (FW) had the strongest explanatory power of 52% (P < 0.05). The medical resources were important ecological factors after 24 months, and the percentage of medical technicians (PMT) had the strongest explanatory power of 70% (P < 0.05). Conclusion: The natural environmental factors and medical resources factors are important ecological factors determining the spatial pattern. The government should strengthen medical and technician construction in North China, comprehensively control fluoride in water, optimize the allocation of medical resources, and promote the balanced development of regional medicine. [ABSTRACT FROM AUTHOR]

Background Type 2 diabetes mellitus (T2DM) intricately involves disrupted lipid metabolism. Exosomes emerge as carriers of biomarkers for early diagnosis and monitoring. This study aims to identify lipid metabolites in serum exosomes for T2DM diagnosis. Methods Serum samples were collected from newly diagnosed T2DM patients and age and body mass index−matched healthy controls. Exosomes were isolated using exosome isolation reagent, and untargeted/targeted liquid chromatography−tandem mass spectrometry (LC-MS/MS) was used to identify and validate altered lipid metabolites. Receiver operating characteristic curve analysis was used to evaluate the diagnostic value of candidate lipid metabolites. Results Serum exosomes were successfully isolated from both groups, with untargeted LC-MS/MS revealing distinct lipid metabolite alterations. Notably, phosphatidylethanolamine (PE) (22:2(13Z,16Z)/14:0) showed stable elevation in T2DM-serum exosomes. Targeted LC-MS/MS confirmed significant increase of PE (22:2(13Z,16Z)/14:0) in T2DM exosomes but not in serum. PE (22:2(13Z,16Z)/14:0) levels not only positively correlated with hemoglobin A1C levels and blood glucose levels, but also effectively distinguished T2DM patients from healthy individuals (area under the curve = 0.9141). Conclusion Our research sheds light on the importance of serum exosome lipid metabolites in diagnosing T2DM, providing valuable insights into the complex lipid metabolism of diabetes. [ABSTRACT FROM AUTHOR]

Background: High turnover among general practitioners (GPs) is a significant challenge in China's efforts to build a sustainable, effective primary care system, but little data is available to help understand and address this issue. The study was aiming at assessing the intention to leave their posts among a sample of GPs and investigating associated factors. Methods: A cross-sectional survey was conducted between December 12, 2014 and March 10, 2015 in Hubei Province, Central China. A total of 1016 GPs (response rate, 85.67%) were investigated by using a structured self-administered questionnaire. A generalized linear regression model was used to identify the associated factors with turnover intention among GPs. Results: Based on a full score of 24, the average score for GPs' turnover intention was 15.40 (SD = 3.43). 78.35% of the GPs had a moderate or higher level of turnover intention. Six hundred and thirty one (62.37%) GPs had ever been exposed to abuse of any kind (physical assault, 18.92%; verbal abuse, 54.38%; threat, 33.79%; verbal sexual harassment, 22.66%; and physical sexual harassment, 7.59%). Generalized linear regression analysis indicated that GPs who were male; who had a vocational school or higher; who had a temporary work contract; who were with lower level of job satisfaction; who reported higher scores on emotional exhaustion; who had been exposed to higher frequency of workplace violence were expressed higher intention to leave their present positions. Conclusion: This study shows that GP's intention to leave general practices is high in Hubei, China. In addition, the prevalence of workplace violence is high among GPs, particularly in the verbal abuse and threat. Measures such as offering permanent contract status, increasing overall job satisfaction, and improving doctor-patient relationship, are needed to moderate GP's turnover intention in order to maintain the foundation of China's three-tier health system. [ABSTRACT FROM AUTHOR]