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Abstract Background Previous studies on whole grain consumption had inconsistent findings and lacked quantitative assessments of evidence quality. Therefore, we aimed to summarize updated findings using the Burden of Proof analysis (BPRF) to investigate the relationship of whole grain consumption on type 2 diabetes (T2D), colorectal cancer (CRC), stroke, and ischemic heart disease (IHD). Methods We conducted a literature search in the Medline and Web of Science up to June 12, 2023, to identify related cohort studies and systematic reviews. The mean RR (relative risk) curve and uncertainty intervals (UIs), BPRF function, risk-outcome score (ROS), and the theoretical minimum risk exposure level (TMREL) were estimated to evaluate the level of four risk-outcome pairs. Results In total, 27 prospective cohorts were included in our analysis. Consuming whole grain at the range of TMREL (118.5–148.1 g per day) was associated with lower risks: T2D (declined by 37.3%, 95% UI: 5.8 to 59.5), CRC (declined by 17.3%, 6.5 to 27.7), stroke (declined by 21.8%, 7.3 to 35.1), and IHD (declined by 36.9%, 7.1 to 58.0). For all outcomes except stroke, we observed a non-linear, monotonic decrease as whole grain consumption increased; For stroke, it followed a J-shaped curve (the greatest decline in the risk of stroke at consuming 100 g whole grain for a day). The relationships between whole grain consumption and four diseases are all two-star pairs (ROS: 0.087, 0.068, 0.062, 0.095 for T2D, CRC, stroke, and IHD, respectively). Conclusion Consuming 100 g of whole grains per day offers broad protective benefits. However, exceeding this threshold may diminish the protective effects against stroke. Our findings endorse replacing refined grains with whole grains as the main source of daily carbohydrates. Registry and registry number for systematic reviews or meta-analyses We have registered our research in PROSPERO, and the identifier of our meta-analyses is CRD42023447345.

Abstract Introduction Geriatric assessment (GA) is widely used to detect vulnerability in older patients. As this process is time-consuming, prescreening tools have been developed to identify patients at risk for frailty. We aimed to assess whether the Geriatric 8 (G8) or the Korean Cancer Study Group Geriatric Score (KG-7) shows better performance in identifying patients who are in need of full GA. Materials and methods A consecutive series of patients aged ≥ 60 years with colorectal cancer were included. The sensitivity, specificity, predictive value, and 95% confidence intervals (95% CI) were calculated for the G8 and the KG-7 using the results of GA as the reference standard. ROC(Receiver Operating Characteristic) was used to evaluate the accuracy of the G8 and the KG-7. Results One hundred four patients were enrolled. A total of 40.4% of patients were frail according to GA, and 42.3% and 50.0% of patients were frail based on the G8 and the KG-7, respectively. The sensitivity and specificity of the G8 were 90.5% (95% CI: 77.4–97.3%) and 90.3% (95% CI: 80.1–96.4%), respectively. For the KG-7, the sensitivity and specificity were 83.3% (95% CI: 68.6–93.0%) and 72.6% (95% CI: 59.8–83.1%), respectively. Compared to the KG-7, the G8 had a higher predictive accuracy (AUC: (95% CI): 0.90 (0.83–0.95) vs. 0.78 (0.69–0.85); p

Abstract Background Little is known on the association of types of grains with mortality and the moderating effect of lifestyle on this association. This study aims to evaluate the single or joint associations of types of grains and lifestyle with all-cause mortality among Chinese older adults. Methods Data were derived from the Chinese Longitudinal Healthy Longevity Survey (CLHLS) from 1998 to 2018. Subjects aged ≥ 65 years were eligible. The types of grains included wheat, total rice, and coarse cereals. Lifestyle was derived using smoking, alcohol consumption, physical activity, and dietary pattern. All-cause mortality was the primary outcome. Results This study included 30275 participants with a mean age 87 ± 11 years and documented 19261 deaths during a mean follow-up of 4.8 years. Compared to wheat, in those with healthy and intermediate lifestyle, total rice was associated with a 13% (HR: 0.87, 95% CI 0.80, 0.93) and 6% (HR: 0.94, 95% CI 0.90, 1.00) lower risk of mortality, respectively, and coarse cereals were associated with a 14% (HR: 0.86, 95% CI 0.74, 1.00) and 12% (HR: 0.88, 95% CI 0.79, 0.97) lower risk of mortality, respectively. Meanwhile, an increase per SD in intakes of wheat and coarse cereals was associated with a 10% (HR: 1.10, 95% CI 1.03, 1.18) and 25% (HR: 1.25, 95% CI 1.08, 1.44) higher mortality rate in those with healthy lifestyle, and a 13% (HR: 1.13, 95% CI 1.08, 1.19) and 29% (HR: 1.29, 95% CI 1.17, 1.44) higher mortality in females but not males. In addition, a U-shaped association of intake of total grains with all- cause mortality was observed (P for non-linearity = 0.002), and a J-shaped association of intake of total rice with all- cause mortality was observed (P for non-linearity = 0.003). Conclusions Specific types of grains and lifestyle were separately or jointly associated with all-cause mortality. Compared to wheat, total rice and coarse cereals were advanced grains for participants with a relatively healthy lifestyle. Intake of total rice was related to all-cause mortality in a dose–response manner. Therefore, a combination of intermediate intake of total rice and healthy lifestyle should be encouraged in older adults.

Abstract Background Resistance to conventional dose schemes and radiotoxicity of healthy tissue is a clinical challenge in the radiation therapy of large locally advanced drug-resistant gastrointestinal stromal tumor (LADR-GIST). This study aimed to assess the feasibility of using multi-shell Simultaneous Integrated Boost Intensity-Modulated modality (SIB-IMRT) strategy to provide a safe and effective escalation dose regimen for LADR-GIST. Methods 7 patients with LADR-GIST were selected in this study. The modified SIB-IMRT plans for all patients were generated by delivering different escalation-dose gradients to four ring shaped regions (shells) within the gross tumor volume (GTV). The doses of the central volume of the tumor (GTVcenter) were escalated up to 70–92.5 Gy (25 fractions), while the doses of planning target volume (PTV) and shell-1 were kept at 50.0 Gy. Based on different escalation-dose gradients, the modified SIB-IMRT plans were divided into four groups (SIB-IMRT groups). For comparison purposes, plans obtained by conventional IMRT technique (Con-IMRT) with 50 Gy (25 fractions) were also generated for all patients (Con-IMRT group). All plans were normalized to cover 95% of the PTV with the prescribed dose of 50.0 Gy. The equivalent uniform dose (EUD), relative equivalent uniform dose (rEUD), dose volume histogram (DVH), dose profile, conformity index (CI) and monitor unit (MU) were evaluated in five groups. The Friedman Test was performed to determine whether there were significant differences (P

Abstract Background A colorectal cancer screening programme (CCSP) was implemented from 2012 to 2017 in Tianjin, China. Residents with a positive faecal immunochemical test (FIT) or positive self-reported symptom questionnaire (SRSQ) were recommended to undergo colonoscopy. The objective was to investigate the potential factors associated with nonadherence to colonoscopy among a risk-increased population. Methods Data were obtained from the CCSP database, and 199,522 residents with positive FIT or positive SRSQ during two screening rounds (2012–2017) were included in the analysis. Logistic regression analysis was performed to assess the association between nonadherence to colonoscopy and potential predictors. Results A total of 152,870 (76.6%) individuals did not undergo colonoscopy after positive FIT or positive SRSQ. Residents with positive SRSQ but without positive FIT were more likely not to undergo colonoscopy (negative FIT: OR, 2.35; 95% CI, 2.29–2.41, no FIT: OR, 1.27; 95% CI, 1.24–1.31). Patients without a cancer history were less likely to undergo colonoscopy even if they received risk-increased reports based on the SRSQ. Conclusion In the CCSP, seventy-seven percent of the risk-increased population did not undergo colonoscopy. FIT should be recommended since positive FIT results are related to improved adherence to colonoscopy. Residents with negative FIT but positive SRSQ should be informed of the potential cancer risk to ensure adherence to colonoscopy.

Abstract Background Cucumber (Cucumis sativus L.) is an economically important vegetable crop species. However, it is susceptible to various abiotic and biotic stresses. WRKY transcription factors play important roles in plant growth and development, particularly in the plant response to biotic and abiotic stresses. However, little is known about the expression pattern of WRKY genes under different stresses in cucumber. Results In the present study, an analysis of the new assembly of the cucumber genome (v3.0) allowed the identification of 61 cucumber WRKY genes. Phylogenetic and synteny analyses were performed using related species to investigate the evolution of the cucumber WRKY genes. The 61 CsWRKYs were classified into three main groups, within which the gene structure and motif compositions were conserved. Tissue expression profiles of the WRKY genes demonstrated that 24 CsWRKY genes showed constitutive expression (FPKM > 1 in all samples), and some WRKY genes showed organ-specific expression, suggesting that these WRKYs might be important for plant growth and organ development in cucumber. Importantly, analysis of the CsWRKY gene expression patterns revealed that five CsWRKY genes strongly responded to both salt and heat stresses, 12 genes were observed to be expressed in response to infection from downy mildew and powdery mildew, and three CsWRKY genes simultaneously responded to all treatments analysed. Some CsWRKY genes were observed to be induced/repressed at different times after abiotic or biotic stress treatment, demonstrating that cucumber WRKY genes might play different roles during different stress responses and that their expression patterns vary in response to stresses. Conclusions Sixty-one WRKY genes were identified in cucumber, and insight into their classification, evolution, and expression patterns was gained in this study. Responses to different abiotic and biotic stresses in cucumber were also investigated. Our results provide a better understanding of the function of CsWRKY genes in improving abiotic and biotic stress resistance in cucumber.

Abstract Background The occurrence of multiple endocrine neoplasia type 2B (MEN2B) in Asians is very rare. In particular, patients with intractable constipation as the main clinical manifestation are even rarer. Atypical clinical manifestations are likely to lead to a diagnostic delay. In this report, we described a case of a delayed diagnosis of MEN2B, and the first clinical manifestation was intractable constipation. Case presentation A female teenager had suffered from intractable constipation since infancy. Because the colonoscopy and biopsy results from local hospitals did not confirm the presence of congenital megacolon, the girl had been followed up at a local clinic for a long time. The diagnosis was not confirmed until thyroid masses were found in the Pediatric Department of Shanghai Ruijin Hospital when she was 12 years old. According to our detailed evaluation, she suffered from Hirschsprung disease (HD), growth retardation, medullary thyroid carcinoma (MTC) and mucosal neuroma due to a mutation in the RET gene. Thus, the diagnosis of MEN2B was confirmed. Afterward, the girl underwent several surgeries and was still being followed up before the article was published. Conclusion MEN2B has atypical clinical symptoms in the early stage. Refractory constipation may be the only clinical manifestation that lasts for several years. Therefore, we recommend that early screening and gene sequencing should be performed for patients with severe constipation due to HD to determine the cause of the disease and to improve the survival outcome.

Abstract Background The prevalence of general and abdominal obesity has increased rapidly in China. The aims of this study were to estimate the dynamic prevalence of overweight, general obesity, and abdominal obesity and the distribution of body mass index (BMI) and waist circumference (WC) among Chinese adults. Methods Data were obtained from the China Health and Nutrition Survey (CHNS). According to the suggestions of the WHO for Chinese populations, overweight was defined as a 23 kg/m2 ≤ BMI

Abstract Background Psoralen is a coumarin-like and coumarin-related benzofuran glycoside, which is a commonly used traditional Chinese medicine to treat patients with kidney and spleen-yang deficiency symptom. Psoralen has been reported to show estrogen-like activity, antioxidant activity, osteoblastic proliferation accelerating activity, antitumor effects and antibacterial activity. However, the antitumor mechanism of psoralen is not fully understood. This study aimed to investigate the therapeutic efficacy of psoralen in human hepatoma cell line SMMC7721 and the mechanism of antitumor effects. Results Psoralen inhibited proliferation of SMMC7721 in a dose- and time-dependent manner, and promoted apoptosis. Further, psoralen activated the ER stress signal pathway, including the expansion of endoplasmic reticulum, increasing the mRNA levels of GRP78, DDIT3, ATF4, XBP1, GADD34 and the protein levels of GDF15, GRP78, IRE1α, XBP-1s in a time-dependent manner. Psoralen induces cell cycle arrest at G1 phase by enhancing CyclinD1 and reducing CyclinE1 expression. Moreover, TUDC couldn’t inhibit the psoralen-induced ER stress in SMMC7721 cells. Conclusions Psoralen can inhibit the proliferation of SMMC7721 cells and induce ER stress response to induce cell apoptosis, suggesting that psoralen may represent a novel therapeutic option for the prevention and treatment hepatocellular carcinoma.

Abstract Background Dwarfism is a common severe growth disorder, but the etiology is unclear in the majority of cases. Recombinant human growth hormone may be a treatment option, but it has limited efficacy. The currently known laboratory assays do not meet the precision requirements for clinical diagnosis. Here, we have constructed a targeted next-generation sequencing (NGS) panel of selected genes that are suspected to be associated with dwarfism for genetic screening. Methods Genetic screening of 91 children with short stature of unknown etiology was performed with the help of the NGS panel. All the coding regions and exon-intron boundaries of 166 genes were included in the panel. To clarify the pathogenicity of these mutations, their clinical data were reviewed and analyzed. Results The assay identified p.A72G, p.I282V, and p.P491S variants of the PTPN11 gene and a p.I437T variant of the SOS1 gene in 4 cases with Noonan syndrome. A frameshift mutation (p.D2407fs) of the ACAN gene was identified in a case of idiopathic short stature with moderately advanced bone age. A p.R904C variant of the COL2A1 gene was found in a patient, who was accordingly diagnosed with Stickler syndrome. Severe short stature without limb deformity was associated with a p.G11A variant of HOXD13. In addition, we evaluated evidence that a p.D401N variant of the COMP gene may cause multiple epiphyseal dysplasia. Conclusions Our findings suggest that syndromes, particularly Noonan syndrome, may be overlooked due to atypical clinical features. This gene panel has been verified to be effective for the rapid screening of genetic etiologies associated with short stature and for guiding precision medicine-based clinical management.

Abstract Background We aimed to clarify the feasibility of a community-based screening strategy for breast cancer in Tianjin, China; to identify the factors that most significantly influenced its feasibility; and to identify the reference range for quality control. Methods A state-transition Markov model simulated a hypothetical cohort of 100,000 healthy women, the start aged was set at 35 years and the time horizon was set to 50 years. The primary outcome for the model was the incremental cost-utility ratio (ICUR), defined as the program’s cost per quality-adjusted life year (QALY) gained. Three screening strategies providing by community health service for women aged 35 to 69 years was compared regarding to different intervals. Result The probability of the ICUR being below 20 272USD (i.e., triple the annual gross domestic product [3 GDPs]) per QALY saved was 100% for annual screening strategy and screening every three years. Only when the attendance rate was > 50%, the probability for annual screening would be cost effective > 95%. The probability for the annual screening strategy being cost effective could reach to 95% for a willingness-to-pay (WTP) of 2 GDPs when the compliance rate for transfer was > 80%. When 10% stage I tumors were detected by screening, the probability of the annual screening strategy being cost effective would be up to 95% for a WTP > 3 GDPs. Conclusion Annual community-based breast cancer screening was cost effective for a WTP of 3 GDP based on the incidence of breast cancer in Tianjin, China. Measures are needed to ensure performance indicators to a desirable level for the cost-effectiveness of breast cancer screening.

Abstract Background Due to their porous structure and capability to degrade under acidic conditions, CaCO3 nanoparticles in vaterite form can be used as carriers to effectively deliver drugs to low-pH sites such as tumors. The usually used intravenous administration requires long-term vaterite phase and colloidal stability for storage and blood circulation. While passive accumulation in tumors can be achieved via the enhanced permeation and retention effect, active accumulation requires reactive groups on vaterite nanoparticles to conjugate targeting molecules. Both requirements are hard to achieve in one simple and economical vaterite formulation. Herein, we used polyethylenimine (PEI)-based CO2 adduct as both a CO2 source and a template for vaterite mineralization to generate PEI-CO2@CaCO3 colloidal particles, with reactive amino groups from the PEI template. Results The obtained nanoparticles with a hydrodynamic diameter of 200–300 nm have a vaterite phase and colloidal stability in an aqueous solution for over 8 months. These nanoparticles could effectively load anticancer drug doxorubicin via coprecipitation and be surface-modified with polyethylene glycol (PEG) and folic acid for long-term blood circulation and tumor targeting purposes, respectively. After being endocytosed, the PEI-CO2 adduct accelerates the dissolution of drug-loaded nanoparticles to generate CO2 bubbles to break the lysosomes, leading to rapid doxorubicin delivery inside tumor cells. The degradation of PEI-CO2 in the CaCO3 nanoparticles could also release PEI and CO2 and may contribute to the disruption of normal cellular functions. As a result, the drug-loaded PEI-CO2@CaCO3 nanoparticles strongly suppressed tumor growth in mice with HeLa tumor xenografts. Conclusions A new and effective vaterite drug carrier for anticancer therapy has been developed using PEI-CO2 adduct as both a CO2 source and vaterite template for CaCO3 mineralization. This delivery system illustrates an application of CO2 generation materials in drug delivery and has the potential for further development.