Longitudinal screening adherence in the Australian National Bowel Cancer Screening Program from 2006 to 2022.

OBJECTIVE: Australia's National Bowel Cancer Screening Program (NBCSP) offers two-yearly screening to 50-74-year-olds for the prevention and early detection of colorectal cancer (CRC). Internationally, detailed reporting of participation across multiple screening rounds - also known as longitudinal adherence - is becoming more common, but remains limited in Australia. We described the longitudinal screening adherence of individuals by age and sex invited to the NBCSP at least once, and quantified longitudinal adherence among individuals who received four NBCSP invitations. METHODS: We obtained aggregate national data for individuals who received at least one NBCSP invitation between 1 August 2006 and 31 March 2022. We described screening adherence patterns including longitudinal adherence among individuals who received four invitations, and evaluated prior longitudinal adherence and adherence at most recent invitation as predictors of future participation. RESULTS: Over the study period, 8.5 million individuals were invited to screen in the NBCSP; 51.9% of these individuals screened at least once. Of the >2.5 million individuals who received four invitations, 23.3% consistently screened, 38.3% never screened, and 38.3% inconsistently screened. The longitudinal adherence at the fourth invitation round for individuals who previously returned none, one, two, or three of their previous three invitations was 9.5%, 37.4%, 70.1% and 88.8%, respectively. Both longitudinal adherence and adherence at the most recent invitation were significant predictors of future participation. CONCLUSION: Our study is the first detailed report of longitudinal adherence to the NBCSP in >2 screening rounds. These insights into long-term behaviours can inform planning for interventions to improve screening participation.

Novel PATL2 variants cause female infertility with oocyte maturation defect.

PURPOSE: Oocyte maturation defect (OOMD) is a rare cause of in vitro fertilization failure characterized by the production of immature oocytes. Compound heterozygous or homozygous PATL2 mutations have been associated with oocyte arrest at the germinal vesicle (GV), metaphase I (MI), and metaphase II (MII) stages, as well as morphological changes. METHODS: In this study, we recruited three OOMD cases and conducted a comprehensive multiplatform laboratory investigation. RESULTS: Whole exome sequence (WES) revealed four diagnostic variants in PATL2, nonsense mutation c.709C > T (p.R237*) and frameshift mutation c.1486_1487delinsT (p.A496Sfs*4) were novel mutations that have not been reported previously. Furthermore, the pathogenicity of these variants was predicted using in silico analysis, which indicated detrimental effects. Molecular dynamic analysis suggested that the A496S variant disrupted the hydrophobic segment, leading to structural changes that affected the overall protein folding and stability. Additionally, biochemical and molecular experiments were conducted on cells transfected with wild-type (WT) or mutant PATL2 (p.R237* and p.A496Sfs*4) plasmid vectors. CONCLUSIONS: The results demonstrated that PATL2A496Sfs*4 and PATL2R237* had impacts on protein size and expression level. Interestingly, expression levels of specific genes involved in oocyte maturation and early embryonic development were found to be simultaneously deregulated. The findings in our study expand the variation spectrum of the PATL2 gene, provide solid evidence for counseling on future pregnancies in affected families, strongly support the application of in the diagnosis of OOMD, and contribute to the understanding of PATL2 function.

ROR2 promotes invasion and chemoresistance of triple-negative breast cancer cells by activating PI3K/AKT/mTOR signaling.

Objective: This study aimed to investigate the role of receptor tyrosine kinase-like orphan receptor 2 (ROR2) in triple-negative breast cancer (TNBC). Methods: ROR2 expression in primary TNBC and metastatic TNBC tissues was analyzed by immunohistochemical staining and PCR. ROR2 expression in TNBC cell lines was detected by PCR and Western blot analysis. The migration, invasion and chemosensitivity of TNBC cells with overexpression or knockdown of ROR2 were examined. Results: ROR2 expression was high in metastatic TNBC tissues. ROR2 knockdown suppressed the migration, invasion and chemoresistance of TNBC cells. ROR2 overexpression in MDA-MB-435 cells promoted the migration, invasion, and chemoresistance. Moreover, ROR2 knockdown in HC1599 and MDA-MB-435 adriamycin-resistant cells enhanced chemosensitivity to adriamycin. ROR2 could activate PI3K/AKT/mTOR signaling in TNBC cells. Conclusion: ROR2 is upregulated and promotes metastatic phenotypes of TNBC by activating PI3K/AKT/mTOR signaling.

Perceived social support mediates cancer and living meaningfully intervention effects on quality of life after breast cancer surgery.

Aim: To explore the role of perceived social support in enhancing psychological resilience and quality of life in postoperative breast cancer patients. Materials & methods: The Managing Cancer and Living Meaningfully (CALM) intervention was used to improve indicators such as psychological resilience in breast cancer patients, while the role of perceived social support in this was assessed. Results: The intervention group exhibited significant improvements compared with the control group in psychological resilience (F = 9.059, p < 0.01). The analysis showed that increased social support in the control group partly mediated the link between psychological resilience and quality of life. Conclusion: CALM improves overall well-being, indicating that incorporating it into standard care for post-mastectomy patients can positively impact their mental health.

[Box: see text].

Does adjunctive fixation in conjunction with miniplate affect condylar position and morphology after mandibular advancement through bilateral sagittal split ramus osteotomy? A retrospective 3-dimensional CT comparative study.

To minimize condylar positional and morphological changes after mandibular advancement through bilateral sagittal split ramus osteotomy (BSSRO), surgeons add either a bicortical screw or a two-hole plate distal to the conventional single miniplate. Since there have been no previous studies investigating the effect of this combination, our study aimed to evaluate the short- and long-term effects of these adjunctive fixation methods (AFM) on condylar positional and morphological changes after mandibular advancement through BSSRO. This retrospective cohort study included consecutive patients with retruded mandibles who were treated in the Department of Orthognathic and TMJ Surgery at West China Hospital of Stomatology, Sichuan University. The patients were divided into two groups based on the primary predictor variable, which was the addition of AFM - either a single bicortical screw or a two-hole plate in addition to the single miniplate. The primary outcome variable was the condylar positional and morphological changes after mandibular advancement through BSSRO. Three-dimensional facial CT scans were obtained at three different time points (preoperatively - T0, 1 week postoperatively - T1, and 1 year postoperatively - T2) and analyzed using ITK-SNAP, 3D Slicer, and SlicerSALT software. Intergroup comparisons were conducted with an independent t-test, with a p-value of <0.05 considered significant. Correlations between the variables were estimated by Pearson correlation. The study comprised 51 patients (32 females, 19 males; mean age 25.13 ± 4.24 years), involving a total of 81 condyles (21 unilateral and 60 bilateral). There was a significant difference in long-term condylar displacement in favor of AFM along with a single miniplate (p < 0.001). The bicortical screw group recorded less condylar displacement than the two-hole plate group horizontally (0.11 mm vs 0.22 mm) and sagittally (0.03 mm vs 0.17 mm), but more vertically (0.85 mm vs 0.03 mm). Bone formation associated with AFM occurred on all condylar surfaces, compared with only three surfaces in the single miniplate group. The adjunctive method in addition to the single miniplate fixation method showed less condylar displacement and more bone apposition after mandibular advancement through BSSRO. The follow-up duration variable was the only significant determinant for volumetric changes in the condyle.

Development of a novel senescence-related gene signature to predict clinical outcomes, immune landscape, and chemotherapeutic sensitivity in oral squamous cell carcinoma.

BACKGROUND: Cellular senescence significantly associates with tumor initiation, progression, and therapeutic response across multiple cancers. Here, we sought to develop a novel senescence-related genes (SRGs)-derived signature for oral squamous cell carcinoma (OSCC) prognostication and therapeutic response prediction. METHODS: OSCC-specific SRG prognostic signature was established with univariate Cox regression, Kaplan-Meier survival, and LASSO-penalized multivariate Cox regression analyses. A SRG nomogram integrating this signature and selected clinicopathological parameters were constructed by multivariate Cox regression. SiRNA-mediated gene knockdown was exploited to validate its function in vitro. The utilities of SRG signature in predicting immune status and chemotherapeutic sensitivities were analyzed. RESULTS: The prognostic performance of SRG signature/nomogram was satisfactory in multiple independent cohorts. CDK1 knockdown induced senescence phenotype in vitro. Moreover, SRG signature scores negatively correlated with tumor-infiltrating immune cells and associated with multiple chemotherapeutic drug sensitivities. CONCLUSIONS: Our results established SRG-derived signature/nomogram as powerful predictors for prognosis and chemotherapeutic response for OSCC.

The accuracy of virtual surgical planning assisted management for L-shaped reduction malarplasty: A retrospective study.

This study aims to evaluate the accuracy of L-shaped reduction malarplasty with bone setback or resection on the zygoma and the mortice and tenon joint structure on the zygomatic arch under the guidance of virtual surgical planning (VSP). Adult patients with zygomatic protrusion or hypertrophy were enrolled and divided. L-shaped reduction malarplasty with or without bone resection and with the mortice and tenon joint structure on the zygomatic arch was conducted either by digital procedures comprising VSP and three-dimensional (3D) printing titanium templates (Group I) or by conventional methods (Group II). Positions of representative landmarks and superimposition models were analyzed by 3D cephalometry. Satisfaction rate and incidences of clinical complications were compared as well. Satisfactory reduction of zygomatic protrusion or hypertrophy was recognized among all 78 patients. Improved symmetry and great surgical accuracy were observed according to the cephalometry analyses. The bone segment movement of virtual plans and actual results in Group I were measured and showed no obvious difference for the inward movement (5.42 ± 0.98 mm vs. 5.33± 0.93 mm, P = 0.6906) and the sagittal overlap (4.77 ± 1.32 mm vs. 4.87± 1.21 mm, P = 0.7386) at the zygoma roots, along with the step length at the long-arm of the L-shaped osteotomy line (2.43 ± 1.11 mm vs. 2.39± 0.89 mm, P = 0.8665). The high resemblance between virtual plans and actual results was depicted via superimposition models. Meanwhile, a higher satisfaction rate (28 in 36, 78% vs. 20 in 42, 48%) and a lower incidence rate of complications (11 in 36, 31% vs. 21 in 42, 50%) were found in Group I. Within the limitations of the study it seems that the application of VSP in reduction malarplasty could significantly contribute to better surgical accuracy and reduced difficulties in the operation, which would be beneficial to patients with zygoma hypertrophy or prominence.

N6-methyladenosine-modified MIB1 promotes stemness properties and peritoneal metastasis of gastric cancer cells by ubiquitinating DDX3X.

BACKGROUND: Peritoneal metastasis (PM), one of the most typical forms of metastasis in advanced gastric cancer (GC), indicates a poor prognosis. Exploring the potential molecular mechanism of PM is urgently necessary, as it has not been well studied. E3 ubiquitin ligase has been widely established to exert a biological function in various cancers, but its mechanism of action in GC with PM remains unknown. METHODS: The effect of MIB1 on PM of GC was confirmed in vitro and in vivo. Co-immunoprecipitation (Co-IP) and mass spectrometry demonstrated the association between MIB1 and DDX3X. Western blot, flow cytometry and immunofluorescence determined that DDX3X was ubiquitylated by MIB1 and promoted stemness. We further confirmed that METTL3 promoted the up-regulation of MIB1 by RNA immunoprecipitation (RIP), luciferase reporter assay and other experiments. RESULTS: We observed that the E3 ubiquitin ligase Mind bomb 1 (MIB1) was highly expressed in PMs, and patients with PM with high MIB1 expression showed a worse prognosis than those with low MIB1 expression. Mechanistically, our study demonstrated that the E3 ubiquitin ligase MIB1 promoted epithelial-mesenchymal transition (EMT) progression and stemness in GC cells by degrading DDX3X. In addition, METTL3 mediated m6A modification to stabilize MIB1, which required the m6A reader IGF2BP2. CONCLUSIONS: Our study elucidated the specific molecular mechanism by which MIB1 promotes PM of GC, and suggested that targeting the METTL3-MIB1-DDX3X axis may be a promising therapeutic strategy for GC with PM.

Correction between hand hygiene product consumption and hand hygiene compliance in intensive care units of 74 medical institutions in Shanghai / 中国感染控制杂志

Objective To understand the consumption of hand hygiene(HH)products and HH compliance in in-tensive care units(ICUs)of secondary and higher grade medical institutions(MIs)in Shanghai,and provide basis for further monitoring of HH among health care workers(HCWs).Methods Through healthcare-associated infec-tion surveillance system,the consumption of HH products and HH compliance in ICUs from secondary and higher grade MIs in Shanghai in 2017-2021 were analyzed.Results 105 ICUs from 74 MIs were included in analysis,the average consumption of HH products was 79.24(44.88-258.63)mL/(bed·day),with statistically significant difference among different types of ICUs(P＜0.001).The average consumption of HH products increased from 65.75 mL/(bed·day)in 2017 to 87.55 mL/(bed·day)in 2021,showing an increasing trend year by year(P＜0.001).HCWs'HH compliance rate was 82.13％,with the highest in nurses(86.59％)and the lowest(48.90％)in medical technicians,HH compliance rates of HCWs of different occupations were statistically significant different(P＜0.001).Among the implementation modes of HH,39.86％used running water for hand washing,42.27％used alcohol-based hand rub to wipe hands,13.22％didn't take HH measures,and 4.65％didn't take HH mea-sures when wearing gloves,with statistically significant differences among different HH implementation modes of HCWs(P＜0.001).There was a positive correlation between the average consumption of HH products per bed·day and HCWs'HH compliance rate(r=0.703,P＜0.05).Conclusion The average consumption of HH products per bed·day and HH compliance rate of HCWs in ICUs in Shanghai presents an increasing trend year by year.There are differences in the average consumption of HH products per bed·day and HH compliance rate among different types of ICUs.The implementation of HH can be evaluated by continuously surveillance on the average consumption of HH products per bed·day.

Influence of Various Nanomaterials on the Rheology and Hydration Kinetics of Oil Well Cement.

Nanomaterials have great potential to influence the properties of cement-based materials due to their small particle size and large specific surface area. The influences of Nano-SiO2 (NS), gamma-nano-Al2O3 (GNA), alpha-nano-Al2O3 (ANA), and nano-TiO2 (NT) on the rheology and hydration kinetics of class G cement at 30 °C were investigated in this study. The nanomaterials were added in dry powder form at dosages of 1, 2, 3, 5, and 7% by weight of cement (bwoc), and their dispersion was accomplished using polycarboxylate superplasticizer (PCE) at a dosage of 1.6% bwoc. PCE provides a uniform dispersion of nanoparticles in the cement matrix, enhancing the efficiency of nanomaterials. The w/c ratio varied between 0.718 and 0.78 to form a constant-density slurry of 1.65 g/cm3. Our test results showed that NS and GNA caused significant increases in the rheology of the cement slurry, with this effect increasing with dosage, while ANA and NT tended to reduce the rheology of the slurry. Compared to a well-suspended and well-dispersed cement slurry generated by the use of PCE and diutan gum, all nanomaterials can accelerate early hydration by reducing the induction time, with GNA having the strongest influence, while NS was the only nanomaterial that further increased the long-term hydration heat release at 7 days. The stronger effect of NS and GNA on the cement slurry properties can be attributed to their higher chemical reactivity. The dosage effect on total hydration extent was relatively strong for ANA, NT, and NS from 3% to 5% but weak for GNA in the range from 3% to 7%.

The importance of remodeling physiological mandibular angle: mandibular "V-line" versus long curved ostectomy.

BACKGROUND: Numerous surgical options for correcting prominent mandibular angles in East Asians have been reported. The objective of this study is to investigate the importance of remodeling physiological mandibular angle by comparing the surgical effects and complications of mandibular "V-line" ostectomy and long curved ostectomy. METHODS: A retrospective study was conducted on patients who underwent either mandibular "V-line" ostectomy (Group I) or long curved ostectomy (Group II). The outcomes were evaluated using computed tomography (CT) images in combination with medical records and photographs. Data were collected preoperatively and at 6- to 12-month intervals postoperatively. Mandibular angle, posterior mandibular ramus height, radian of the ostectomy line, mandibular symmetry as well as patients' complications were investigated. FACE-Q reports of facial appearance and psychosocial parameters were also compared between the two groups. RESULTS: All 106 patients showed improved lower facial contours. Although the postoperative mandibular angle (116.67±7.14°vs 118.31±6.80°, P=.233) and mandibular symmetry (2.36±1.21mm vs 2.56±1.19mm, P=.395) were similar in the two groups, larger postoperative posterior mandibular height and lower radian of the ostectomy line were observed in Group I (P < .001). Physiological mandibular angle was also remodeled in Group I. The gonial deficiency, more soft tissue sagging and significant lower FACE-Q scores of facial appearance were observed in Group II (P < .001). CONCLUSION: In conclusion, "V-line" ostectomy is better suited for achieving a more physiological mandibular angle with less complications compared to mandibular long curved ostectomy. When it comes to mandibular contouring, "V-line" ostectomy may be the preferred option.

H3K27 acetylation activated-CD109 evokes 5-fluorouracil resistance in gastric cancer via the JNK/MAPK signaling pathway.

Drug resistance is a considerable obstacle to gastric cancer (GC) treatment. The current work aimed to elucidate the functional mechanism of CD109 in 5-fluorouracil (5-FU) resistance in GC. In this study, we demonstrated that CD109 was extremely heightened in 5-FU-resistant GC cells. CD109 deficiency lessened the IC50 value, impaired cell viability and metastatic capability, and induced cell apoptosis after 5-FU treatment in cells. In addition, we found that PAX5 bound p300 increased the enrichment of H3K27ac at the promoter region of the CD109 gene, which resulted in the upregulation of CD109 in GC. Moreover, we also revealed that CD109 triggered 5-FU resistance via activating the JNK/MAPK signaling. Blockage of JNK/MAPK signaling using JNK inhibitor, SP600125, abolished CD109 upregulation-induced changes of IC50 values, cell viability, metastasis and apoptosis in NCI-N87/5-FU and SNU-1/5-FU cells. Importantly, CD109 silencing enhanced the therapeutic efficacy of 5-FU, leading to reduced tumor growth in vivo. In conclusion, our results unveiled that H3K27 acetylation activated-CD109 enhanced 5-FU resistance of GC cells via modulating the JNK/MAPK signaling pathway, which might provide an attractive therapeutic target for GC.

Music therapy, quality of life and efficacy of immunotherapy for NSCLC.

OBJECTIVE: Our study examines how non-small cell lung cancer (NSCLC) survivors undergoing immunotherapy can experience reduced anxiety and psychological distress, improved quality of life (QOL) and increased immunotherapy efficacy. METHODS: 133 men and 20 women with NSCLCs were enrolled. In a randomised controlled trial involving a care as usual group (CG) and a music therapy group (MTG), the researchers employed various tools such as the Self-Rating Anxiety Scale, Symptom Distress Thermometer, Functional Assessment of Cancer Therapy-General version 4 and Response Evaluation Criteria in Solid Tumours. These measures were used to evaluate anxiety, psychological distress, QOL and immunotherapy efficacy in patients undergoing immunotherapy before and after patients' completion. RESULTS: After the intervention, patients in the MTG demonstrated a noteworthy reduction in anxiety (t=6.272, p≤0.001) and distress (t=10.111, p≤0.001), as well as an increase in QOL (t=-7.649, p≤0.001). Moreover, compared with patients in the CG, those in the MTG demonstrated a remarkable drop in anxiety (t=-4.72, p≤0.001) and distress (t=-7.29, p≤0.001), a significant increase in QOL (t=5.363, p≤0.001) and a significant improvement in immunotherapy efficacy (z=-2.18, p≤0.05) after the intervention. CONCLUSIONS: The use of individual music therapy sessions appears to be effective in reducing anxiety and distress, while also increasing QOL and immunotherapy efficacy in patients with NSCLCs undergoing immunotherapy.

A Predictive Model for the Early Death of Breast Cancer With Synchronous Liver Metastases: A Population-Based Study.

BACKGROUND: Breast cancer liver metastasis (BCLM) is a severe condition often resulting in early death. The identification of prognostic factors and the construction of accurate predictive models can guide clinical decision-making. METHODS: A large sample of data from the Surveillance, Epidemiology, and End Results (SEER) database was analyzed, including 3711 patients diagnosed with de novo BCLM between 2010 and 2015. Predictive models were developed using histograms, and stepwise regression addressed variable collinearity. Internal validation was performed, and results were compared to similar studies. RESULTS: In this study of 3711 BCLM patients, 2571 didn't have early death. Out of the 1164 who died early, 1086 had cancer-specific early death. Prognostic factors for early death, including age, race, tumor size, and lymph node involvement, were identified. A nomogram based on these factors was constructed, accurately predicting early all-cause and cancer-specific death. CONCLUSIONS: Valuable insights into the prognosis of BCLM patients were provided, and important prognostic factors for early death were identified. The developed nomogram can assist clinicians in identifying high-risk patients for early death and inform treatment decisions.

Advances in the study of the molecular biological mechanisms of radiation-induced brain injury.

Radiation therapy is one of the most commonly used treatments for head and neck cancers, but it often leads to radiation-induced brain injury. Patients with radiation-induced brain injury have a poorer quality of life, and no effective treatments are available. The pathogenesis of this condition is unknown. This review summarizes the molecular biological mechanism of radiation-induced brain injury and provides research directions for future studies. The molecular mechanisms of radiation-induced brain injury are diverse and complex. Radiation-induced chronic neuroinflammation, destruction of the blood-brain barrier, oxidative stress, neuronal damage, and physiopathological responses caused by specific exosome secretion lead to radiation-induced brain injury.

Evaluation of neoadjuvant immunotherapy plus chemotherapy in Chinese surgically resectable gastric cancer: a pilot study by meta-analysis.

Background: Recently, the use of immunochemotherapy in the treatment of advanced gastric cancer (GC) has been increasing and programmed cell death protein 1 (PD-1) inhibitors combined with chemotherapy has become the first-line treatment for advanced GC. However, few studies with small sample sizes have examined this treatment regimen to assess its effectiveness and safety in the neoadjuvant treatment phase of resectable local advanced GC. Materials and methods: Herein, we systematically searched PubMed, Cochrane CENTRAL, and Web of Science for clinical trials on neoadjuvant immunochemotherapy (nICT) in advanced GC. The primary outcomes were effectiveness [evaluated by major pathological response (MPR) and pathological complete response (pCR)] and safety [assessed by grade 3-4 treatment-related adverse events (TRAEs) and postoperative complications]. A meta-analysis of non-comparative binary results was performed to aggregate the primary outcomes. Direct comparative analysis was used to compare pooled results of neoadjuvant chemotherapy (nCT) with nICT. The outcomes emerged as risk ratios (RR). Results: Five articles with 206 patients were included, and all of them were from the Chinese population. The pooled pCR and MPR rates were 26.5% (95% CI: 21.3%-33.3%) and 49.0% (95% CI: 42.3%-55.9%), while grade 3-4 TRAEs and post-operative complication rates were 20.0% (95% CI: 9.1%-39.8%) and 30.1% (95% CI: 23.1%-37.9%), respectively. Direct comparison showed that with the exception of grade 3-4 TRAEs and postoperative complications, all outcomes including pCR, MPR, and R0 resection rate favoured nICT to nCT. Conclusion: nICT is a promising strategy for use as an advisable neoadjuvant treatment for patients with advanced GC in Chinese population. However, more phase III randomized controlled trials (RCTs) will be required to further consolidate the efficacy and safety of this regimen.

Peritoneal high-fat environment promotes peritoneal metastasis of gastric cancer cells through activation of NSUN2-mediated ORAI2 m5C modification.

Peritoneal metastasis (PM) is an important metastatic modality of gastric cancer (GC).It is associated with poor prognosis. The underlying molecular mechanism of PM remains elusive. 5-Methylcytosine (m5C), a posttranscriptional RNA modification, involves in the progression of many tumors. However, its role in GC peritoneal metastasis remains unclear. In our study, transcriptome results suggested that NSUN2 expression was significantly upregulated in PM. And patients with high NSUN2 expression of PM predicted a worse prognosis. Mechanistically, NSUN2 regulates ORAI2 mRNA stability by m5C modification, thereby promoting ORAI2 expression and further promoting peritoneal metastasis and colonization of GC. YBX1 acts as a "reader" by binding to the ORAI2 m5C modification site. Following the uptake of fatty acids from omental adipocytes by GC cells, the transcription factor E2F1 was upregulated, which further promoted the expression of NSUN2 through cis-element. Briefly, these results revealed that peritoneal adipocytes provide fatty acid for GC cells, thus contributing to the elevation of E2F1 and NSUN2 through AMPK pathway, and upregulated NSUN2 activates the key gene ORAI2 through m5C modification, thereby promoting peritoneal metastasis and colonization of gastric cancer.

Early prenatal exposure to air pollutants and congenital heart disease: a nested case-control study.

BACKGROUND: Congenital heart disease (CHD) is one of the most common congenital malformations in humans. Inconsistent results emerged in the existed studies on associations between air pollution and congenital heart disease. The purpose of this study was to evaluate the association of gestational exposure to air pollutants with congenital heart disease, and to explore the critical exposure windows for congenital heart disease. METHODS: The nested case-control study collected birth records and the following health data in Tianjin Women and Children's Health Center, China. All of the cases of congenital heart disease from 2013 to 2015 were selected matching five healthy controls for each case. Inverse distance weighting was used to estimate individual exposure based on daily air pollution data. Furthermore, the conditional logistic regression with distributed lag non-linear model was performed to identify the association between gestational exposure to air pollution and congenital heart disease. RESULTS: A total of 8,748 mother-infant pairs were entered into the analysis, of which 1,458 infants suffered from congenital heart disease. For each 10 µg/m3 increase of gestational exposure to PM2.5, the ORs (95% confidence interval, 95%CI) ranged from 1.008 (1.001-1.016) to 1.013 (1.001-1.024) during the 1st-2nd gestation weeks. Similar weak but increased risks of congenital heart disease were associated with O3 exposure during the 1st week and SO2 exposure during 6th-7th weeks in the first trimester, while no significant findings for other air pollutants. CONCLUSIONS: This study highlighted that gestational exposure to PM2.5, O3, and SO2 had lag effects on congenital heart disease. Our results support potential benefits for pregnancy women to the mitigation of air pollution exposure in the early stage, especially when a critical exposure time window of air pollutants may precede heart development.

Shift work and nonalcoholic fatty liver disease incidence among Chinese rail workers: a 4-year longitudinal cohort study.

PURPOSE: Occupational harmful factors, such as shift work, are attracting increasing attention as a potential cause of nonalcoholic fatty liver disease (NAFLD). In this study, we aimed to identify the association between shift work and NAFLD incidence in Chinese rail population. METHODS: A cohort study was conducted among 14,112 rail workers for 4-year follow-up. Shift work frequency and other potential variables were recorded by questionnaires, including demographic, lifestyle, and occupation information. Besides, body mass index, blood pressure, fasting blood glucose, total cholesterol, triglyceride, alanine aminotransferase, and aspartate aminotransferase were measured by anthropometric measurement and blood test. Diagnosis of new NAFLD case was based on abdominal ultrasonography. Cox proportional hazards regression model was used to determine whether shift work has effect on occurrence of NAFLD. RESULTS: The incidence of NAFLD was 30.43% in total subjects. After adjustment for possible confounders, the RRs of NAFLD were 1.069 (95% CI 0.998-1.146) and 1.179 (95% CI 1.059-1.312) in occasionally shift work group and frequently shift work group respectively, compared to the seldom shift work group. In stratified analyses, the RRs of NAFLD incidence linked to shift work exposure seems increase among female and elder. The results of three sensitivity analyses were similar with main analysis. CONCLUSIONS: This research provided further evidence of positive harmful effect of shift work on NAFLD incidence in Chinese rail workers, particularly in frequently shift work population. The risk estimate of shift work on NAFLD was higher in female and elder.

Function of a non-enzymatic hexokinase LcHXK1 as glucose sensor in regulating litchi fruit abscission.

Fruit abscission is a severe hindrance to commercial crop production, and a lack of carbohydrates causes fruit abscission to intensify in a variety of plant species. However, the precise mechanism by which carbohydrates affect fruit setting potential has yet to be determined. In the current study, we noticed negative correlation between hexose level and fruit setting by comparing different cultivars, bearing shoots of varying diameters, and girdling and defoliation treatments. The cumulative fruit-dropping rate was significantly reduced in response to exogenous glucose dipping. These results suggested that hexose, especially glucose, is the key player in lowering litchi fruit abscission. Moreover, five putative litchi hexokinase genes (LcHXKs) were isolated and the subcellular localization as well as activity of their expressed proteins in catalyzing hexose phosphorylation were investigated. LcHXK2 was only found in mitochondria and expressed catalytic protein, whereas the other four HXKs were found in both mitochondria and nuclei and had no activity in catalyzing hexose phosphorylation. LcHXK1 and LcHXK4 were found in the same cluster as previously reported hexose sensors AtHXK1 and MdHXK1. Furthermore, VIGS-mediated silencing assay confirms that LcHXK1 suppression increases fruit abscission. These findings revealed that LcHXK1 functions as hexose sensor, negatively regulating litchi fruit abscission.