Genome-wide association studies and Mendelian randomization analyses provide insights into the causes of early-onset colorectal cancer.

BACKGROUND: The incidence of early-onset colorectal cancer (EOCRC; diagnosed <50 years of age) is rising globally; however, the causes underlying this trend are largely unknown. CRC has strong genetic and environmental determinants, yet common genetic variants and causal modifiable risk factors underlying EOCRC are unknown. We conducted the first EOCRC-specific genome-wide association study (GWAS) and Mendelian randomization (MR) analyses to explore germline genetic and causal modifiable risk factors associated with EOCRC. PATIENTS AND METHODS: We conducted a GWAS meta-analysis of 6176 EOCRC cases and 65 829 controls from the Genetics and Epidemiology of Colorectal Cancer Consortium (GECCO), the Colorectal Transdisciplinary Study (CORECT), the Colon Cancer Family Registry (CCFR), and the UK Biobank. We then used the EOCRC GWAS to investigate 28 modifiable risk factors using two-sample MR. RESULTS: We found two novel risk loci for EOCRC at 1p34.1 and 4p15.33, which were not previously associated with CRC risk. We identified a deleterious coding variant (rs36053993, G396D) at polyposis-associated DNA repair gene MUTYH (odds ratio 1.80, 95% confidence interval 1.47-2.22) but show that most of the common genetic susceptibility was from noncoding signals enriched in epigenetic markers present in gastrointestinal tract cells. We identified new EOCRC-susceptibility genes, and in addition to pathways such as transforming growth factor (TGF) ß, suppressor of Mothers Against Decapentaplegic (SMAD), bone morphogenetic protein (BMP) and phosphatidylinositol kinase (PI3K) signaling, our study highlights a role for insulin signaling and immune/infection-related pathways in EOCRC. In our MR analyses, we found novel evidence of probable causal associations for higher levels of body size and metabolic factors-such as body fat percentage, waist circumference, waist-to-hip ratio, basal metabolic rate, and fasting insulin-higher alcohol drinking, and lower education attainment with increased EOCRC risk. CONCLUSIONS: Our novel findings indicate inherited susceptibility to EOCRC and suggest modifiable lifestyle and metabolic targets that could also be used to risk-stratify individuals for personalized screening strategies or other interventions.

Apparent diffusion coefficient and its standard deviation from diffusion-weighted imaging in preoperative predicting liver invasion by T3-staged resectable gallbladder carcinoma.

AIM: To evaluate apparent diffusion coefficient (ADC) and its standard deviation (SDADC) in preoperative predicting liver invasion by T3-staged gallbladder carcinoma (GBC). MATERIALS AND METHODS: Forty-one consecutive patients with T3-staged resectable GBC were included and divided into two sets with (n=27) and without (n=14) liver invasion. All patients underwent DWI at b-values of 0, 20, 50, 80, 100, 200, 400, 600, 800, and 1,000 s/mm2 with a 3 T magnetic resonance imaging scanner before surgery. ADC and SDADC of tumour-adjacent and tumour-distant liver tissues were measured on DWI, and were compared by Mann-Whitney U-tests. If there was a significant difference in any derived parameter, the area under the receiver operating characteristic curve (AUC) was used to assess performance of this parameter to predict liver invasion. RESULTS: DWI could differentiate between patients with and without liver invasion when b = 0, 1,000 s/mm2 (AUCs of ADC and SDADC were 0.697 and 0.714, respectively). In patients with liver invasion, mean ADC and SDADC of tumour-adjacent liver tissue were lower than of tumour-distant liver tissue when b = 0, 800 s/mm2, and = 0, 1,000 s/mm2 (all p-values <0.05). To differentiate tumour-adjacent from tumour-distant liver tissues in patients with liver invasion, AUCs of ADC were 0.687 (b = 0, 800 s/mm2) and 0.680 (b = 0, 1,000 s/mm2), and AUCs of SDADC were 0.673 (b = 0, 800 s/mm2) and 0.731 (b = 0, 1,000 s/mm2). CONCLUSIONS: DWI could have potential value in preoperative predicting liver invasion by T3-staged GBC.

Factors associated with hepatitis B knowledge among people of Vietnamese ethnicity in Australia.

Despite high hepatitis B (HBV) prevalence among people of Vietnamese ethnicity in Australia and elsewhere, there is limited research on levels of HBV knowledge and factors associated with such knowledge. The aim of this study was to examine HBV knowledge and associated demographic and attitudinal factors among people of Vietnamese ethnicity in Australia. People of Vietnamese ethnicity (n = 966) were recruited through community events and social media groups to complete online surveys measuring HBV knowledge, attitudes towards HBV, levels of mistrust in Western medicine, and demographic characteristics. Findings of this study indicate that levels of knowledge are mixed, with gaps in knowledge related to transmission and treatment of the virus. Those with greater knowledge of HBV tended to be older, have higher levels of formal education, have been tested for HBV, and know someone living with HBV. Those with lower levels of knowledge tended to have more negative attitudes towards the virus and greater levels of mistrust in Western medicine. Given that health literacy is connected to effective communication from health providers, we suggest that there is a need for the development of health promotion and education resources targeted at people of Vietnamese ethnicity and translated into Vietnamese. We propose that such resources be developed in consultation with Vietnamese communities and health providers to ensure that they are culturally appropriate and sensitive to people of Vietnamese ethnicity living in Australia.

[Clinical study on the efficacy and safety of glaucoma drainage implants in the treatment of different types of glaucoma].

Objective: To evaluate the efficacy and safety of glaucoma drainage implants(XEN-45 Gel Stent) for glaucoma treatment. Methods: A prospective study was conducted to continuously collect the clinical data of patients who were diagnosed with glaucoma and underwent XEN-45 Gel Stent implantation in the Ophthalmology Department of Peking University People's Hospital from January 2022 to August 2023. The visual acuity, intraocular pressure, number of glaucoma medications, and success rate of the patients were analyzed before and after surgery at 1 day, 1 week, 1 month, 3 months, 6 months, 12 months, and 18 months. The differences in intraocular pressure and number of glaucoma medications among primary open-angle glaucoma, primary angle closure glaucoma, secondary glaucoma, and different implantation methods of XEN-45 Gel Stent among patients with primary open-angle glaucoma were compared. The intraoperative and postoperative complications were observed, and the risk factors for needling and surgical complete success were analyzed. Results: A total of 48 eyes from 48 patients were included in this study, comprising 27 males and 21 females, with a mean age of (54.4±18.0) years and the disease duration was 36.0(7.3, 81.0) months.There were 28 cases of primary open-angle glaucoma, 4 cases of primary angle closure glaucoma, and 16 cases of secondary glaucoma.The follow-up period was 8.0 (3.0, 12.0) months. At 12 months after surgery, the intraocular pressure decreased from 20.5 (17.0, 26.0) mmHg to (13.5±3.3) mmHg (P<0.05), and the number of glaucoma medications decreased from 3.0 (3.0, 4.0) to 0.0 (0.0, 0.0) (P<0.05). The complete success rate and qualified success rate were 73.9% (17/23) and 91.3% (21/23), respectively. The most common postoperative complications were shallow anterior chamber in 6 cases (12.5%), hypotony in 3 cases (6.3%), and blocked stent in 3 cases (6.3%). The most common postoperative treatment was needling in 27 cases (56.3%). There was no significant difference in intraocular pressure among different types of glaucoma. In the comparison of postoperative effects of different surgical implantation methods for primary open-angle glaucoma, there were no statistically significant differences in intraocular pressure and the number of glaucoma medications at other follow-up time points except 1 month after surgery (P<0.05). Univariate logistic regression analysis did not find any risk factors associated with needling and surgical complete success. Conclusions: XEN-45 Gel Stent implantation is an effective and safe surgical option for different types of glaucoma patients in China, which can significantly reduce intraocular pressure and the use of glaucoma medications and has a high success rate. However, some patients may need needling or other treatments after surgery.

[The effect of the AIM2 inflammasome in noise-induced cognitive dysfunction in rats].

Objective: To explore the effect of the absent in melanoma 2 (AIM2) -mediated neuroinflammation in noise-induced cognitive dysfunction in rats. Methods: In April 2023, sixteen male Wistar rats were randomly divided into control group and noise group, with 8 rats in each group. The rats in the noise group were placed in 50 cm×50 cm×40 cm transparent boxes and exposed to 100 dB (A) white noise with a sound pressure level of 100 dB (A) (4 h/d for 30 d) . At the same time, rats in the control group were kept in similar boxes with environmental noise less than 60 dB (A) . After 30 days of noise exposure, the Morris water maze experiment was applied to test the learning and memory abilities of the rats; the pathological morphology of hippocampal tissues was observed by Hematoxylin-Eosin (HE) staining. Western blot was used to detect the protein expression levels of AIM2, cysteinyl aspartate specific proteinase-1 (caspase-1) , apoptosis-associated speck-like protein (ASC) , interleukin-1ß (IL-1ß) , IL-18, ionic calcium-binding articulation molecule-1 (Iba-1) , and glial fibrillary acidic protein (GFAP) . The expression of both Iba-1 and GFAP in hippocampal tissue was assessed by immunohistochemical staining. The co-localization of AIM2 with Iba-1 or GFAP was determined by immunofluorescence double staining. Results: Compared with the control group, the escape latency of rats in the noise group was increased by 16.29 s, 17.71 s, and 20.26 s on days 3, 4, and 5, respectively. On day 6, the noise-exposed rats spent shorter time in the target quadrant and had fewer times in crossing the platform[ (7.25±2.27) s and (1.13±0.64) times] than the control group[ (15.64±3.99) s and (4.25±2.12) times] (P<0.05) . After noise exposure, hippocampal neurons of rats displayed marked nuclear hyperchromatic and pyknosis phenomenon. The noise-exposed rats had higher numbers of both microglia and astrocytes (27.00±2.65 and 43.33±5.51) in the DG area of the hippocampus relative to the control group (14.67±3.06 and 20.00±4.58) (P<0.05) . Moreover, the glial cells in the noise group had larger cell cytosol with more and thicker branches. The protein expression levels of inflammatory cytokines Cleaved-IL-1ß and Cleaved-IL-18 in the hippocampus of rats in the noise group (1.55±0.19 and 1.74±0.12) were significantly higher than the control group (1.00±0.11 and 1.00±0.13) (P<0.05) . After noise exposure, the protein expression levels of AIM2, Cleaved-Caspase-1 and ASC (1.19±0.09, 1.34±0.07 and 1.14±0.01) were higher than the control group (1.00±0.07, 1.00±0.14 and 1.00±0.06) and differences between the two groups were statistically significant (P<0.05) . A significant increase in the number of cells co-localizing AIM2 with Iba-1 or GFAP in the noise group (28.67±4.04 and 40.67±5.13) compared with the control group (15.67±4.04 and 17.67±3.79) , and statistically significant differences were observed between the two groups (P<0.05) . Conclusion: Noise exposure may activate the AIM2 inflammasome in hippocampal glial cells of rats, releasing excessive inflammatory cytokines and causing neuroinflammation that damages neurons.

[Safety and efficacy analysis of endovascular thrombectomy in patients with large vascular occlusion with low Alberta Stroke Program Early Computed Tomography Score].

Objective: To evaluate the safety and efficacy of endovascular thrombectomy (EVT) in acute anterior circulation large vessel occlusive stroke (ALVOS) and explore the related influencing factors for prognoses in patients with low Alberta Stroke Program Early Computed Tomography Score (ASPECT). Methods: Patients with acute ALVOS who underwent EVT in Yijishan Hospital of Wannan Medical College from January 2019 to June 2022 were sequentially enrolled. (1) Patients were divided into a low ASPECT group (0-5) and a non-low ASPECT group (6-10), and the differences between the two groups were compared with respect to incidence of perioperative complications and good prognosis rate [modified Rankin scale (mRS) score≤2] 90 days after onset. (2) According to the prognoses 90 days after onset, the low ASPECT group was divided into the good prognosis (mRS score≤2) and poor prognosis (mRS score>2) subgroup. Univariate analysis and multivariate logistic regression analysis were used to investigate the independent risk factors for prognoses of the low ASPECT patients after EVT. Results: A total of 582 patients [age 26-94(69±11) years, 345 male patients (59.3%)] were enrolled for analysis. The baseline ASPECT score was 8 (7, 10), and the baseline NIHSS score was 14 (11, 18). Among them, 102 (17.5%) patients were in the low ASPECT score group and 480 (82.5%) patients were in the non-low ASPECT score group. In the total cohort, patients in the low ASPECT score group had a higher incidence of symptomatic intracranial hemorrhage, lower 90-day good prognosis rate, and higher 90-day mortality rate. Further, propensity score matching statistical analysis showed that patients in the low ASPECT score group had a significantly higher incidence of malignant brain edema after EVT treatment (40.0% vs. 17.6%, χ2=9.13, P=0.003), and a significantly lower 90-day good prognosis rate (24.7% vs. 41.6%, χ2=4.96, P=0.026), but there was no significant difference in the incidence of symptomatic intracranial hemorrhage and 90-day mortality between the two groups (40.3% vs. 26.0%, χ2=3.55, P=0.060). Among 102 patients with low ASPECT score, 22 (21.6%) patients had good prognosis and 80 (78.4%) had poor prognosis. Multivariate logistic regression analysis showed that history of atrial fibrillation (OR=4.478, 95%CI 1.186-16.913, P=0.027) was an independent risk factor for poor prognosis of EVT in patients with low ASPECT score, while good collateral circulation (grade 2 vs. grade 0: OR=0.206, 95%CI 0.051-0.842, P=0.028) was a protective factor for good prognosis of EVT in patients with low ASPECT score. Conclusions: Although the 90-day good prognosis rate of EVT treatment for patients with low ASPECT score was lower than that of the non-low ASPECT group, 21.6% patients still benefitted from EVT treatment, especially patients with non-atrial fibrillation and good collateral circulation. Future studies involving more patients are needed to validate our observations.

[Effects of biologics on psychological status and quality of life in patients with inflammatory bowel disease: a multicenter study].

Objective: To investigate the effects of biologics on psychological status and quality of life in patients with inflammatory bowel disease (IBD). Methods: A cross-sectional survey was conducted in 42 hospitals in 22 provinces (autonomous regions and municipalities directly under the central government) from September 2021 to May 2022. General clinical information and the use of biologics were obtained from adult patients diagnosed with IBD who voluntarily participated in the study. Psychological status was evaluated using the Generalized Anxiety Disorder (GAD-7), Patient Health Questionnaire-9 (PHQ-9), Pittsburgh Sleep Quality Index (PSQI), and Inflammatory Bowel Disease Questionnaire (IBDQ) assessment tools. Counts were analyzed via the Chi-square test, and datasets that were not normally distributed were analyzed via nonparametric tests. P<0.05 was considered statistically significant. Results: A total of 2 478 valid questionnaires were collected. The GAD-7 score of the biologics group was significantly lower than that of the non-use group [6 (2, 9) vs. 7 (3, 10), Z=-3.49, P<0.001]. IBDQ scores [183 (158, 204) vs. 178 (152, 198), Z=-4.11, P<0.001], intestinal symptom scores [61 (52, 67) vs. 58 (49, 65), Z=-5.41, P<0.001], systemic symptom scores [28 (24, 32) vs. 27 (23, 31), Z=-2.37, P=0.018], emotional ability scores [69 (58, 77) vs. 67 (56, 75), Z=-3.58, P<0.001] and social ability scores [26 (22, 29) vs. 25 (22, 29), Z=-2.52, P=0.012] in the biologics group were significantly higher than in the non-use group. GAD-7 scores [5 (2, 9) vs. 6 (3, 10), Z=-3.50, P<0.001] and PSQI scores [6 (4, 9) vs. 6 (4, 9), Z=-2.55, P=0.011] were significantly lower in the group using infliximab than in the group not using it. IBDQ scores were significantly higher in patients using vedolizumab than in those not using it [186 (159, 205) vs. 181 (155, 201), Z=-2.32, P=0.021] and were also significantly higher in the group treated with adalimumab than in the group not treated with adalimumab [187 (159, 209) vs. 181 (155, 201), Z=-2.16, P=0.030]. However, ustekinumab had no significant effect on any of the scores. Conclusion: The use of biologics is strongly associated with improvements in anxiety status and quality of life in IBD patients.

[Retrospective analysis of associated factors and adverse pregnancy outcomes of postpartum hemorrhage in the caesarean section of different types of placenta previa].

Objective: To analyze associated factors and adverse pregnancy outcomes of postpartum hemorrhage in the caesarean section of puerperae with different types of placenta previa. Methods: This retrospective research was a case-control study. Puerperae with cesarean section of placenta previa from January 2019 to December 2020 in Women's Hospital, School of Medicine, Zhejiang University were collected and divided into the<1 000 ml control group or ≥1 000 ml postpartum hemorrhage group according to the amount of blood loss during cesarean section. Differences in continuous variables were analyzed by t-test and categorical variables were analyzed by χ2 test. The risk factors of postpartum hemorrhage were analyzed by logistic multivariate regression. Results: A total of 962 puerperae were enrolled with 773 cases in the control group and 189 cases in the postpartum hemorrhage group. The incidence of gestational weeks, gravidity, parity, induced abortion, placental accreta and preoperative hemoglobin<110 g/L was significantly different between two groups in different types of placenta previa (P<0.001). Logistic multivariate regression model analysis showed that the independent risk factors of postpartum hemorrhage in the caesarean section of low-lying placenta included placental accreta (OR=12.713, 95%CI: 4.296-37.625), preoperative hemoglobin<110 g/L (OR=2.377, 95%CI: 1.062-5.321), and prenatal vaginal bleeding (OR=4.244, 95%CI: 1.865-9.656). The independent risk factors of postpartum hemorrhage in the caesarean section of placenta previa included once induced abortion (OR=2.789, 95%CI:1.189-6.544), induced abortion≥2 (OR=2.843, 95%CI:1.101-7.339), placental accreta (OR=6.079, 95%CI:3.697-9.996), HBsAg positive (OR=3.891, 95%CI:1.385-10.929), and placental attachment to the anterior uterine wall (OR=2.307, 95%CI:1.285-4.142). The rate of postpartum hemorrhage and premature delivery in puerperae with placenta previa was higher than that in puerperae with low-lying placenta (P<0.001). Conclusions: The associated factors of postpartum hemorrhage in puerperae with different types of placenta previa are different. Placenta accreta is the common risk factor of postpartum hemorrhage in puerperae with low-lying placenta and placenta previa.

Experimental Limits on Exotic Spin and Velocity Dependent Interactions Using Rotationally Modulated Source Masses and an Atomic-Magnetometer Array.

Various theories beyond the standard model predict new interactions mediated by new light particles with very weak couplings to ordinary matter. Interactions between polarized electrons and unpolarized nucleons proportional to g_{V}^{N}g_{A}^{e}σ[over →]·v[over →] and g_{A}^{N}g_{A}^{e}σ[over →]·v[over →]×r[over →] are two such examples, where σ[over →] is the spin of the electrons, r[over →] and v[over →] are position and relative velocity between the polarized electrons and nucleons, g_{V}^{N}/g_{A}^{N} is the vector or axial-vector coupling constant of the nucleon, and g_{A}^{e} is the axial-vector coupling constant of the electron. Such interactions involving a vector or axial-vector coupling g_{V}^{N}/g_{A}^{N} at one vertex and an axial-vector coupling g_{A}^{e} at the polarized electron vertex can be induced by the exchange of spin-1 bosons. We report new experimental upper limits on such exotic spin-velocity-dependent interactions of the electron with nucleons from dedicated experiments based on a recently proposed scheme. We rotationally modulated two ∼6 Kg source masses at a frequency of 20 Hz. We used four identical atomic magnetometers in an array form to increase the statistics and cancel the common-mode noise. We applied a data processing method based on high precision numerical integration for the four harmonic frequencies of the signal. We reverse the rotation direction of the source masses to flip the signal due to the new interactions; thus, we can apply the [+1,-3,+3,-1] weighting method to remove possible slow drifting. Our constraint on the product of vector and axial-vector couplings is |g_{V}^{N}g_{A}^{e}|<2.1×10^{-34} and on the product of axial-vector and axial-vector couplings is |g_{A}^{N}g_{A}^{e}|<2.4×10^{-22} for an interaction range of 10 m. The new constraints on vector-axial-vector interaction improved by as much as more than 4 orders of magnitude and on axial-axial interaction by as much as 2 orders of magnitude in the corresponding interaction range, respectively.

ToTEM: A software for fast TEM image simulation.

ToTEM, a multislice-based image simulation software is developed for transmission electron microscope (TEM). This software implements the following major features: (i) capability of assigning three-dimensional potentials of atom into multiple slices and precise introduction of phase shift caused by the sub-pixel atomic position, (ii) employing CUDA coding and graphical processing units (GPU) with multithreading parallel algorithm based on the powerful batch (inverse) fast Fourier transform (FFT), which is especially beneficial for image simulation of scanning transmission electron microscopy (STEM) or (integrated) differential phase contrast (I)DPC, (iii) design for efficiently generating large batch of data set of high-resolution transmission electron microscopy (HRTEM) images. Image simulation acceleration for STEM has been verified by simulating a large-scale SrTiO3 . Additionally, iDPC image of MFI-type zeolites with xylene molecules encapsulated in straight channels demonstrates the advantage of iDPC in detecting light molecules.

[Correlation between serum IgM antibody and viral load with clinical symptoms in neonates infected with cytomegalovirus].

To investigate the correlation between serum cytomegalovirus (CMV) IgM antibody/viral load and infection-related clinical symptoms in neonates infected with CMV, and provide basis for clinical assessment and monitoring of neonatal CMV infection. A total of 70 neonates with CMV infection admitted to neonatology in Women's Hospital, School of Medicine Zhejiang University, from January 2014 to December 2020 were included in this study. Using real-time quantitative PCR as the diagnostic criteria, congenital cytomegalovirus-infected neonates (n=29) was diagnosed within the first 3 weeks of life, otherwise, it was postnatally acquired cytomegalovirus infection (n=41). The differences in general information and clinical indicators between IgM antibody positive and negative patients were analyzed, combined with the PCR result, the correlation between the IgM/viral load and the occurrence of symptoms were analyzed. T-test and non-parametric test were used to compare the differences of indicators between groups, logistic regression was used for multivariate analysis, and ROC curve was used to evaluate the auxiliary diagnostic value of relevant indicators. In the congenital CMV infection group and the postnatally acquired CMV infection group, viral load and the proportion of symptomatic patients in IgM positive group were significantly higher than IgM negative group (Z=-2.616, P=0.008; 80% vs. 21%, P=0.005) (Z=-2.405, P=0.016; 56% vs. 19%, P=0.025). Logistic regression analysis of the included population showed the risk factors of CMV infection-related symptoms were IgM positive (OR 4.562, 95%CI:1.461-14.246,P=0.009) and viral load (OR 1.728, 95%CI:1.068-2.798,P=0.026). Regressive analysis for single symptom with correction showed IgM antibody positive was associated with hearing dysfunction(OR 3.954, 95%CI:1.066-14.677,P=0.040),the CMV viral load was associated with thrombocytopenia (OR 2.228, 95%CI:1.124-4.413,P=0.022), and brain imaging abnormalities (OR 3.956, 95%CI:1.421-11.011, P=0.008). Receiver operating characteristic (ROC) analysis showed the area under ROC curve of CMV viral load for brain imaging abnormalities was 0.883 (P<0.001), with a sensitivity of 75.0% and specificity of 90.3%. For neonates infected with CMV, the risk of infection-related clinical symptoms and hearing dysfunction may be increased when IgM antibody was positive. Meanwhile, the higher the CMV viral load at diagnosis, the higher the risk of thrombocytopenia and abnormal brain imaging.

[Exploring the effects of artesunate and fuzheng huayu decoction on mitochondria in the treatment of schistosomiasis liver fibrosis].

Objective: To compare the effects of artesunate (Art) and fuzheng huayu decoction on mitochondrial autophagy in the treatment of schistosomiasis liver fibrosis. Methods: Eighty C57BL/6 female mice were randomly divided into healthy control group, infection group, Art treatment group and Fuzheng Huayu Decoction treatment group, with 20 mice in each group. Mice in the infection group and treatment group were infected with 16 Schistosoma japonicum cercariae. After 6 weeks, praziquantel (300 mg/kg) was used for 2 days to kill the worms. The Art treatment group was treated with intraperitoneal injection of 100 mg/kg/day, while the Fuzheng Huayu Decoction treatment group was fed 16g of fuzheng huayu decoction per 1kg per day. After 6 weeks, fresh liver tissues of the four groups were collected. Masson staining and Western blot were used to observe the succinate dehydrogenase subunit A (SDHA) and malate dehydrogenase (MDH2), citrate synthase (CS), ketoglutarate dehydrogenase (OGDH), and target of rapamycin 1 (mTORC1) pathway involved in mitochondrial tricarboxylic acid cycle in liver tissues. The relative expression levels of adenylate activated protein kinase (AMPK) and mitochondrial autophagy pathway kinase (PINK1) were detected. Liver tissue samples were extracted from each group to detect the mitochondrial oxygen consumption rate. Two-way ANOVA was used to compare the significance and difference between two sets of samples. Results: Masson staining showed that the infection group mice had significantly higher liver fibrosis area than the healthy control group, while the Art treatment group and Fuzheng Huayu Decoction treatment group mice had lower liver fibrosis area than the infection group. Western blot analysis showed that the infection group (0.82 ± 0.05) had significantly lower relative expression of SDHA protein than the healthy control group (1.00 ± 0.05) (t = 11.23, P = 0.0035), while the Art treatment group (0.73 ± 0.05) had significantly higher relative expression of SDHA protein than the infection group (t = 10.79, P = 0.0073). However, there was no significant change in Fuzheng Huayu Decoction treatment group (0.98±0.05) (t = 1.925, P = 0.1266). The relative expression of p-AMPK protein was significantly higher in the infection group (1.15 ±0.05) than in the healthy control group (0.98 ± 0.07, t = 12.18, P = 0.0029), and the expression of p-AMPK in the Art treatment group (0.50 ± 0.05) was significantly lower than the infection group (t = 11.78, P = 0.0032). The relative protein expression of AMPK was significantly lower in the infection group (0.80 ± 0.05) than in the healthy control group (1.00 ± 0.05, t = 10.53, P = 0.0046). The expression of AMPK was significantly lower in the Art treatment group (0.54 ± 0.05) than in the infection group (T = 13.98, P = 0.0036). The relative expression of p-mTORC1 protein (0.93 ± 0.08) was not significantly different in the infection group than in the healthy control group (t = 2.28, P = 0.065), while the Art treatment group (0.63 ± 0.05) had significantly lower relative expression of p-mTORC1 protein than the infection group (t = 10.58, P = 0.029). The expression of p-mTORC1/ m-TORC1 was not significantly different in the infection group (0.98 ± 0.03) than in the healthy control group (0.97 ± 0.03, t = 0.98, P = 0.085), while the Art treatment group (0.63 ± 0.05) had significantly lower relative expression of p-mTORC1/ m-TORC1 than the infection group (t = 14.58, P = 0. 009). The relative protein expression of PINK1 was significantly lower in the infection group (0.55 ± 0.05) than in the healthy control group (1.00 ± 0.03, t = 13.49, P = 0.0011), while the Art treatment group (1.21 ± 0.05, t = 9.98, P = 0.0046) and Fuzheng Huayu Decoction treatment group (1.31 ±0.35, t = 6.98, P = 0.027) had significantly higher relative protein expression of PINK1 than the infection group. Mitochondrial function tests showed that after adding substrate complex II, the oxygen consumption of the infection group was lower than the healthy control group, while the Art treatment group and the Fuzheng Huayu Decoction treatment group had higher oxygen consumption than the infection group. The oxygen consumption was significantly lower after adding the substrate complex III in the infection group than the healthy control group, while the Art treatment group and Fuzheng Huayu Decoction treatment group had higher oxygen consumption than the infection group. Conclusion: Art can alleviate schistosomiasis liver fibrosis by inhibiting AMPK/mTORC1 signaling pathway activity and enhancing mitochondrial oxygen consumption, autophagy and SDHA expression.

[Application of three risk assessment methods to noise risk assessment in an automobile foundry enterprise].

Objective: To explore the applicability of three different kinds of noise occupational health risk assessment methods to the occupational health risk assessment of noise exposed positions in an automobile foundry enterprise. Methods: In July 2020, the occupational-health risk assessment of noise-exposed positions was conducted by using the Guidelines for risk management of occupational noise hazard (guideline method) , the International Commission on Mining and Metals Guidelines for Occupational Health Risk Assessment (ICMM) method and the Occupational-health risk index method (index method) respectively, and the results were analyzed and compared. Results: Through the occupational health field investigation, the noise exposure level of the enterprise's main workstations was between 80.3 and 94.8 dB (A) , among which the noise of the posts of shaking-sand, cleaning and modeling was greater than 85 dB (A) ; The noise risk of each position was evaluated by the three methods, and the adjustment risk level was between 2 and 5 assessed using the guideline method, between 2 and 3 assessed using the index method, and 5 evaluated using the ICMM model. Conclusion: Each of the three risk assessment methods has its own advantages and disadvantages. The ICMM model has a large difference in value assignment, and values in the results are larger than expected. The evaluation results of the guideline method and the index method are consistent in some positions, there is certain subjectivity in the evaluation using the index method, and the guideline method is more objective.

Prospective evaluation of dietary and lifestyle pattern indices with risk of colorectal cancer in a cohort of younger women.

BACKGROUND: Although colorectal cancer (CRC) incidence in the USA is declining overall, its incidence is increasing among those younger than 50 years of age. The reasons underlying the increasing trend are largely unknown, although behavioral changes, such as unhealthy diet and lifestyle factors, may be partially responsible. DESIGN: A prospective cohort study included 94 217 women aged 26-45 years at baseline. Validated anthropometric measures and lifestyle information were self-reported biennially. Exposures were four recommendation-based dietary indices-the prime diet quality score and three plant-based dietary indices; and two mechanism-based indices-the empirical dietary and lifestyle index for hyperinsulinemia (EDIH and ELIH). We calculated hazard ratios (HRs) and 95% confidence intervals (CIs) for overall CRC and for early-onset (before age 50) and after age 50 CRC separately. RESULTS: We documented 332 cases of CRC during 24 years of follow-up (2 113 655 person-years), with an average age of 52 ± 7 years at diagnosis. Hyperinsulinemic dietary and lifestyle patterns were associated with a higher risk of CRC. Multivariable-adjusted HRs (95% CIs) comparing participants in the highest versus lowest quartile were: 1.67 for EDIH (95% CI: 1.15-2.44, P-trend = 0.01) and 1.51 for ELIH (95% CI: 1.10-2.08, P-trend = 0.01). Moreover, per 75% increment in rank, ELIH appeared to be a stronger risk factor for early-onset CRC (HR = 1.86, 95% CI: 1.12-3.07) than after age 50 CRC (HR = 1.20, 95% CI: 0.83-1.73, P-heterogeneity = 0.16). The four recommendation-based indices were not significantly associated with overall, early-onset, or after age 50 CRC risk (per 75% increment in rank, HRs ranged from 0.75 to 1.28). CONCLUSION: Dietary and lifestyle patterns contributing to hyperinsulinemia were associated with greater CRC risk in younger women. Moreover, the hyperinsulinemic lifestyle showed a suggestively stronger positive association with early-onset CRC risk, compared with after age 50 CRC. Our findings suggest that dietary and lifestyle interventions to reduce insulinemic potential may be effective for CRC prevention among younger women.

Testosterone use and shorter electrocardiographic QT interval duration in men living with and without HIV.

OBJECTIVES: Testosterone usage (T-use) may alter risk factors for sudden cardiac death in men living with HIV (MLWH). Electrocardiographic QT interval prolongation, which could potentiate ventricular arrhythmias, has previously been associated with HIV infection and, separately, with low testosterone levels. We investigated whether T-use shortens the QT interval duration in MLWH and HIV-uninfected men. METHODS: We utilized data from the Multicenter AIDS Cohort Study, a prospective, longitudinal study of HIV infection among men who have sex with men. Multivariable linear regression analyses were used to evaluate associations between T-use and corrected QT interval (QTc) duration. RESULTS: Testosterone usage was more common in MLWH compared with HIV-uninfected men (19% vs. 9%). In a multivariable regression analysis, T-use was associated with a 5.7 ms shorter QT interval [95% confidence interval (CI): -9.5 to -1.9; P = 0.003). Furthermore, stronger associations were observed for prolonged duration of T-use and recent timing of T-use. CONCLUSIONS: This study is the first known analysis of T-use and QTc interval in MLWH. Overall, our data demonstrate that recent T-use is associated with a shorter QTc interval. Increased T-use duration above a threshold of ≥ 50% of visits in the preceding 5 years was associated with a shorter QTc interval while lesser T-use duration was not.

Gene polymorphisms of pro-inflammatory cytokines may affect the risk of Graves' disease: a meta-analysis.

PURPOSE: Gene polymorphisms of pro-inflammatory cytokines such as tumor necrosis factor-α (TNF-α), interleukin-1 (IL-1) and interleukin-6 (IL-6) may influence the risk of Graves' disease, but the results of so far published studies remain inconclusive. Therefore, the authors conducted this meta-analysis to assess relationships between TNF-α/IL-1/IL-6 polymorphisms and the risk of Graves' disease by pooling the findings of all relevant studies. METHODS: A comprehensive literature searching of Pubmed, Embase, Web of Science and CNKI was conducted by the authors, and twenty-eight studies were found to be eligible for pooled analyses. RESULTS: The pooled meta-analyses results showed that genotypic frequencies of TNF-α rs1800629, IL-1A rs1800587, IL-6 rs1800795 and IL-6 rs1800796 polymorphisms among patients with Graves' disease and control subjects differed significantly. Moreover, we found that genotypic frequencies of TNF-α rs1800629 and IL-6 rs1800795 polymorphisms among patients with Graves' disease and control subjects in Caucasians differed significantly, and genotypic frequencies of IL-1A rs1800587, IL-1B rs16944, IL-6 rs1800795 and IL-6 rs1800796 polymorphisms among patients with Graves' disease and control subjects in Asians also differed significantly. Nevertheless, we did not detect such genotypic frequencies differences for TNF-α rs361525 and IL-1B rs1143627 polymorphisms. CONCLUSIONS: This meta-analysis suggests that TNF-α rs1800629, IL-1A rs1800587, IL-6 rs1800795 and IL-6 rs1800796 polymorphisms may influence the risk of Graves' disease in overall population. Moreover, TNF-α rs1800629 and IL-6 rs1800795 polymorphisms may influence the risk of Graves' disease in Caucasians, while IL-1A rs1800587, IL-1B rs16944, IL-6 rs1800795 and IL-6 rs1800796 polymorphisms may influence the risk of Graves' disease in Asians.

[Choices of emergency treatment and surgical method for ruptured abdominal aortic aneurysms].

Objective: To investigate the emergency management process of ruptured abdominal aortic aneurysm (RAAA), and analyze the perioperative mortality factors of different surgical methods. Methods: The emergency data and hospitalization data of 91 patients with ruptured abdominal aortic aneurysm in Xiangya Hospital of Central South University from June 2010 to June 2019 were retrospectively analyzed.Twelve of the patients died preoperatively due to excessive blood loss, and the remaining 79 patients were hospitalized for open surgery (OSR) or endovascular repair (EVAR).The differences in age, time to hospital arrival, emergency preparation time, first creatinine value, emergency infusion volume, preoperative drop in blood pressure, preoperative use of vasoactive drugs and iliac artery involvement were compared between preoperative death group (n=12) and preoperative survival group (n=79), OSR group (n=50) and EVAR group (n=29), postoperative death group (n=23) and postoperative survival group (n=56). Results: Seventy-nine patients received open surgery or endovascular repair, and 23 died after operation. Age, time to hospital arrival, first creatinine value and emergency infusion volume were (77±11) years, (18±5)h, (469±150) µmol/L, (4 140±1 743) ml in the preoperative death group and (70±10) years, (12±8) h, (228±174) µmol/L, (1 358±1 211) ml in the preoperative survival group, respectively, and the differences were statistically significant (all P<0.05). There were no significant differences in preoperative data, intraoperative treatment and postoperative perioperative mortality between the open surgery group and the endovascular repair group (all P>0.05). The intraoperative blood loss, operation time and aortic occlusion rate in the endovascular repair group were 100 (50, 175) ml, (3.2±0.9) h, 13.8%, respectively, which were better than that in the open surgery group 1700 (600, 3425) ml, (5.2±1.1) h, 100%. The differences were statistically significant (all P<0.05). Age, emergency preparation time, first creatinine value, emergency infusion volume, blood pressure decline rate and vasoactive drug utilization rate in the death group were (77±8) years, (4.1±1.7) h, (456±172) µmol/L, (2 024±1 687) ml, 100%, 100%, respectively, and (68±10) years, (2.7±2.2) h, (135±26) µmol/L, (1 085±825) ml, 21.4%, 12.5% in the survival group, respectively. The differences were statistically significant (all P<0.05). Conclusions: Age, emergency preparation time, first creatinine value, emergency infusion volume, decreased blood pressure and use of vasoactive drugs are all associated with perioperative death in patients with ruptured abdominal aortic aneurysm. EVAR surgery is a better choice if conditions exist.

[Status and clinical response of fertility preservation in young patients with breast cancer].

Cancer treatments may improve the long-term survival rate of young patients with breast cancer, but also lead to a decrease in fertility. With the younger incidence of breast cancer in China, the fertility needs of this group have received more attention, and fertility preservation technology suitable for cancer patients is developing continuously. However, there are still many problems in the implementation of fertility preservation for young breast cancer patients in China. Patients and breast surgeons have insufficient understanding and conservative attitudes towards fertility preservation technology. And there is a lack of reproductive experts in the treatment process. What's more, the long-term follow-up and information management of patients undergoing fertility preservation are defective. In response to the above, this paper discusses how to deal with patients with potential reproductive needs in clinical practice from the perspective of breast surgeons. The first is to improve their own understanding of fertility preservation, such as the progress of relevant technologies and applicable population, when to intervene, when and how to get pregnant after cancer treatment. Secondly, education for patients must be strengthened, which should include not only fertility preservation, but also scientific contraceptive methods during cancer treatment and treatment measures for unexpected pregnancy. Finally, hospitals and relevant units should standardize the multidisciplinary team of breast cancer, and strengthen the comprehensive management of young breast cancer patients, thus to provide young breast cancer patients with more scientific cancer treatment programs and more reproductive opportunities.

[Analysis on related factors of myocardial fibrosis in patients with hypertrophic cardiomyopathy].

Objective: To investigate the related factors of myocardial fibrosis in patients with hypertrophic cardiomyopathy. Methods: Patients with hypertrophic cardiomyopathy, hospitalized in the First People's Hospital of Yunnan Province from January 2016 to May 2020, were included in this cross-sectional study. Patients were divided into delayed enhancement positive group (fibrosis group) and non-delayed enhancement group (non-fibrosis group). According to the maximum left ventricular end diastolic wall thickness (LVMWT), patients in the fibrosis group was further divided into mild hypertrophy group, moderate hypertrophy group and severe hypertrophy group. The baseline clinical data of patients were collected by medical record management system. All enrolled patients underwent cardiac magnetic resonance imaging (CMR). The presence and location of myocardial fibrosis were identified by CMR gadolinium contrast delayed enhancement (LGE). The range of LGE (LGE%) was calculated by visual analysis. The levels of N-terminal pro-B-type natriuretic peptide (NT-proBNP) and cardiac troponin I (cTnI) in peripheral blood were measured. Results: A total of 48 patients ( age (46.4±14.3) years, 42 (87.5%) males) were enrolled. There were 34 LGE positive cases (fibrosis group) and 14 LGE negative cases (non-fibrosis group). Compared with non-fibrosis group, patients in fibrosis group were younger (P=0.038) and prevalence of NYHA grade Ⅲ/Ⅳ was higher (P=0.00). Compared with non-fibrosis group, patients in fibrosis group had thicker LVMWT (P= 0.008), higher left ventricular mass index(LVMI) (P=0.001), higher left ventricular end diastolic volume (LVEDV) (P=0.043), lower left ventricular ejection fraction (LVEF) and cardiac index (CI) (all P <0.05). The levels of NT-proBNP and cTnI were significantly higher in fibrosis group than in non-fibrosis group (2 760.5 (1 503.4, 3 783.6) ng / L vs. 861.3 (552.2, 1 092.8) ng / L, P=0.002; 0.970 (0.448, 1.684)µg / L vs. 0.147 (0.033, 0.251)µg / L, P=0.041).In fibrosis group, there were 15 cases of mild hypertrophy (mild hypertrophy group), 10 cases of moderate hypertrophy (moderate hypertrophy group), and 9 cases of severe hypertrophy (severe hypertrophy group). The LGE% and NT-proBNP and cTnI increased in proportion with increasing myocardial hypertrophy (P<0.05). LGE% was negatively correlated with age (r=-0.618, P=0.011), and positively correlated with NT-proBNP and cTnI levels (r=0.271, P=0.010; r=0.111,P=0.013, respectively), and positively correlated with LVEDV, LVMWT and LVMI (r=0.438, P=0.09; r=0.735, P=0.001; r=0.532, P=0.034, respectively). Conclusions: In patients with hypertrophic cardiomyopathy, the extent of myocardial fibrosis increases with the increase of myocardial hypertrophy. Myocardial fibrosis is negatively correlated with age, and positively correlated with NT-proBNP and cTnI, as well as LVEDV, LVMWT and LVMI in this patient cohort.

[Cumulative noise exposure and the risk of high-frequency hearing loss relationships].

Objective: To explore the dose-response relationship between cumulative noise exposure and high-frequency hearing loss, and further to provide a basis for the control of occupational hazards of noise. Methods: A Meta-analysis of dose-response relationships was performed on the data of eligible literatures published in China from January 2000.1 to December 2019.12. Results: The initial combined Odds Ratio (OR) and its 95%CI in the Meta-analysis were 1.10 (1.08-1.12) . As the Begg's funnel plot and Egger's test indicated publication bias (t=5.97, P<0.01) , the Trim-and-Fill Method was used for OR value adjustment. The adjusted-OR was 1.09 (1.07-1.12) ; sensitivity analysis showed that the results of this Meta-analysis have high stability; subgroup analysis indicated that the ORs of the steady-state noise group and the non-steady-state noise group were 1.10 (1.08-1.12) and 1.14 (1.07-1.21) , the ORs of the old standard group and the new standard group were 1.10 (1.08-1.12) and 1.11 (1.00-1.24) , respectively. The nonlinear dose-response relationship curve demonstrated that the risk of high-frequency hearing loss increases rapidly after CNE reaches 95 dB (A) ·years. Conclusion: There is a definite dose-response relationship between CNE and high-frequency hearing loss, which can be used to predict the risk of high-frequency hearing loss in noisy workers.