[Analysis of the application effect and safety of transnasal humidified rapid insufflation ventilatory exchange technique in hysteroscopic diagnostic and therapeutic surgery].

Objective: To investigate the effect and safety of transnasal humidified rapid insufflation ventilatory exchange (THRIVE) technique in hysteroscopic diagnostic and therapeutic surgery. Methods: This study was a randomized controlled trial. A total of 100 female patients undergoing hysteroscopy surgery at Beijing Tongren Hospital from September to December 2023 were selected and randomly divided into two groups by the random number table method: the THRIVE group and the mask oxygen group, with 50 patients in each group. Patients in both groups were given total intravenous anesthesia with propofol combined with remifentanil and preserved spontaneous respiration. The THRIVE group was given oxygen by the THRIVE device with an oxygen flow rate of 50 L/min, while the mask oxygen group was given oxygen by the mask with an oxygen flow rate of 5 L/min; the oxygen concentration of both groups was set at 100%. The general condition of the patients, vital signs during the operation, the amount of anesthesia drugs used and the operation time were recorded. The primary observation index was the incidence of hypoxic events in the two groups; the secondary observation indexes were the incidence and time of intraoperative apnea as well as the corresponding oxygenation interventions and the incidence of non-hypoxic adverse events. Results: The age of the THRIVE group was (42±14) years, and the age of the mask oxygen group was (43±15) years. The duration of surgery in the THRIVE group was (15.9±3.4) min, which was statistically lower than that of the mask oxygen group (16.3±4.5) min (P=0.041), and there were no differences observed in the duration of awakening time and anesthesia time (both P>0.05). There was no significant difference in the dosage of propofol, remifentanil, and intraoperative vasoactive drugs between the two groups (all P>0.05). The SpO2 of the patients in the THRIVE group at the end of the operation was (99.7±1.1) %, which was higher than that of the mask-oxygen group (99.1±1.1) % (P<0.05). There was no difference in SpO2 of the two groups at the other time points (all P>0.05). There were no differences in HR and MAP of two group patients at each time point (all P>0.05). The incidence of hypoxic events in the THRIVE group was 12.0% (6/50), which was lower than that of 28.0% (14/50) in the mask oxygen group (P=0.045). The difference in the incidence and duration of apnea between the two groups was not statistically significant (all P>0.05). There were no cases of temporary need for laryngeal mask or tracheal intubation during surgery in both groups. There was no statistically significant difference in the incidence of intraoperative body movement, dizziness, nausea and vomiting between the two groups (all P>0.05), and no cardiac, cerebral, renal or other important organ insufficiency occurred in the two weeks after surgery. Conclusion: THRIVE technology can provide effective oxygenation for patients undergoing hysteroscopic diagnosis and treatment, maintain patients' circulatory stability, and improve the safety and efficiency of surgery.

[Metabolic study of iron deposition based on magnetic resonance in patients with nonalcoholic fatty liver disease].

Objective: To explore the relationship between liver iron deposition and steatosis in patients with non-alcoholic fatty liver disease (NAFLD) through MRI. Methods: 163 cases of liver biopsy underwent MRI examination. R2* was used to measure liver iron content. Dixon-based proton density fat fraction (PDFF) was used to measure liver fat content. One-way ANOVA, r-correlation, ROC curve, and others were used to assess the relationship between clinical case data, serological indices, and imaging results in accordance with the pathological results of the liver biopsy. Results: R2* gradually increased as the pathological steatosis grade rose. The R2* that corresponded to no steatosis (< 5%), mild steatosis (14.95%±8.55%), moderate steatosis (46.30%±9.32%), and severe steatosis (73.86%±6.35%) were 27.56±4.40, 31.06±5.95, 38.06±4.80, and 48.10±5.55 (P < 0.001), respectively. There was a positive correlation between R2* and liver steatosis content (r= 0.769, P < 0.05). The area under the ROC curve and cut-off value were 0.88 and 31.77, respectively, and there was no distinct relationship with liver inflammation or fibrosis. Conclusion: R2* can quantitatively and non-invasively evaluate liver iron deposition in patients with NAFLD. A distinct relationship exists between liver steatosis and iron deposition, and iron deposition tends to increase as the steatosis aggravates.

[The core techniques of airway and circulation management in eye and ear-nose-throat anesthesia].

With the continuous update of anesthesia techniques, equipment and research field, the techniques and concepts of anesthesia in eye and ear-nose-throat (ENT) surgery are constantly optimized and developed. Eye and ENT anesthesia has its unique technical characteristics and problems. By reviewing related literature extensively and combining with our experience, this article analyzed and discussed the challenges of ENT anesthesia, such as difficult airway, airway hyperactivity, controlled hypotension and so on, as well as summarizing and evaluating the advantages and disadvantages of the techniques applied in ENT anesthesia.

[Survival analysis of long-term HIV/AIDS cases aged 15 years and over under antiretroviral treatment in Henan Province from 2002 to 2020].

Objective: To analyze the survival and influencing factors of HIV infections and AIDS cases (HIV/AIDS) aged 15 years and over who had received antiretroviral treatment (ART) for more than 10 years in Henan Province. Methods: In this retrospective cohort study, data of HIV infections and AIDS cases in Henan province were collected from the AIDS Prevention and Control System between January 1, 2002 and December 31, 2020. This study included 20 256 participants alive after 10-year ART with complete baseline and follow-up information, such as demographic characteristics, CD4+T lymphocyte count and viral load. Cox proportional risk regression model was used to analyze influencing factors of HIV/AIDS survival. Results: A total of 20 256 participants were followed up for 82 738.2 person-years, with an average follow-up of 4.1 person-years, of which most cases were blood transmission (85.5%) and married (71.2%). The male to female ratio was 1∶1.06 and the age at 10 years of ART was (51.2±8.7) years old. About 88.5% of HIV/AIDS patients received ART in village/township treatment institutions. Overall, there were 2 030 deaths during this period, among which 1 897 were due to AIDS-related diseases (93.5%) and the case fatality rate was 9.4% (1 897/20 256). Cox proportional risk regression model showed that participants aged 40-54, 55-69, and ≥70 years had a higher risk of death compared to those aged 25-39, with adjusted HRs (95%CI) of 1.57 (1.19-2.08), 3.78 (2.86-4.99), and 6.17 (4.33-8.79), respectively. Participants with the initial CD4+T lymphocyte count about 200-349/µl and<200/µl had a higher risk of death compared to those with initial CD4+T lymphocyte count ≥350/µl, with adjusted HRs (95%CI) of 1.81 (1.61-2.04) and 3.64 (3.20-4.15), respectively. Participants with the initial viral load outcome ≥1 000 copies/ml had a higher risk of death compared to those with the initial viral load outcome<1 000 copies/ml, with adjusted HRs (95%CI) of 1.73 (1.52-1.97). Participants receiving the second-line ART had a lower risk of death compared to those receiving the first-line ART, with adjusted HRs (95%CI) of 0.12 (0.11-0.14). Conclusion: From 2002 to 2020, the survival rate of HIV/AIDS treated with ART for more than 10 years is high in Henan Province. Age, CD4+T lymphocyte count and viral load are influencing factors of HIV/AIDS survival.

Single-cell RNA sequencing identifies molecular targets associated with poor in vitro maturation performance of oocytes collected from ovarian stimulation.

STUDY QUESTION: What is the transcriptome signature associated with poor performance of rescue IVM (rIVM) oocytes and how can we rejuvenate them? SUMMARY ANSWER: The GATA-1/CREB1/WNT signalling axis was repressed in rIVM oocytes, particularly those of poor quality; restoration of this axis may produce more usable rIVM oocytes. WHAT IS KNOWN ALREADY: rIVM aims to produce mature oocytes (MII) for IVF through IVM of immature oocytes collected from stimulated ovaries. It is not popular due to limited success rate in infertility treatment. Genetic aberrations, cellular stress and the absence of cumulus cell support in oocytes could account for the failure of rIVM. STUDY DESIGN, SIZE, DURATION: We applied single-cell RNA sequencing (scRNA-seq) to capture the transcriptomes of human in vivo oocytes (IVO) (n = 10) from 7 donors and rIVM oocytes (n = 10) from 10 donors. The effects of maternal age and ovarian responses on rIVM oocyte transcriptomes were also studied. In parallel, we studied the effect of gallic acid on the maturation rate of mouse oocytes cultured in IVM medium with (n = 84) and without (n = 85) gallic acid. PARTICIPANTS/MATERIALS, SETTING, METHODS: Human oocytes were collected from donors aged 28-41 years with a body mass index of <30. RNA extraction, cDNA generation, library construction and sequencing were performed in one preparation. scRNA-seq data were then processed and analysed. Selected genes in the rIVM versus IVO comparison were validated by quantitative real-time PCR. For the gallic acid study, we collected immature oocytes from 5-month-old mice and studied the effect of 10-µM gallic acid on their maturation rate. MAIN RESULTS AND THE ROLE OF CHANCE: The transcriptome profiles of rIVM/IVO oocytes showed distinctive differences. A total of 1559 differentially expressed genes (DEGs, genes with at least 2-fold change and adjusted P < 0.05) were found to be enriched in metabolic processes, biosynthesis and oxidative phosphorylation. Among these DEGs, we identified a repression of WNT/ß-catenin signalling in rIVM when compared with IVO oocytes. We found that oestradiol levels exhibited a significant age-independent correlation with the IVO mature oocyte ratio (MII ratio) for each donor. rIVM oocytes from women with a high MII ratio were found to have over-represented cellular processes such as anti-apoptosis. To further identify targets that contribute to the poor clinical outcomes of rIVM, we compared oocytes collected from young donors with a high MII ratio with oocytes from donors of advanced maternal age and lower MII ratio, and revealed that CREB1 is an important regulator. Thus, our study identified that GATA-1/CREB1/WNT signalling was repressed in both rIVM oocytes versus IVO oocytes and in rIVM oocytes of lower versus higher quality. Consequently we investigated gallic acid, as a potential antioxidant substrate in human rIVM medium, and found that it increased the mouse oocyte maturation rate by 31.1%. LARGE SCALE DATA: Raw data from this study can be accessed through GSE158539. LIMITATIONS, REASONS FOR CAUTION: In the rIVM oocytes of the high- and low-quality comparison, the number of samples was limited after data filtering with stringent selection criteria. For the oocyte stage identification, we were unable to predict the presence of oocyte spindle, so polar body extrusion was the only indicator. WIDER IMPLICATIONS OF THE FINDINGS: This study showed that GATA-1/CREB1/WNT signalling was repressed in rIVM oocytes compared with IVO oocytes and was further downregulated in low-quality rIVM oocytes, providing us the foundation of subsequent follow-up research on human oocytes and raising safety concerns about the clinical use of rescued oocytes. STUDY FUNDING/COMPETING INTEREST(S): This work was supported by the Collaborative Research Fund, Research Grants Council, C4054-16G, and Research Committee Funding (Research Sustainability of Major RGC Funding Schemes), The Chinese University of Hong Kong. The authors have no conflicts of interest to declare.

Comparison of a covered metallic ureteral stent and a double-J stent for malignant ureteral obstruction in advanced gastric cancer.

AIM: To compare the patency and safety of covered metallic stents (CMS) and the double-J stent (DJS) for treating malignant ureteral obstruction (MUO) in advanced gastric cancer (AGC). MATERIALS AND METHODS: Between 2016 and 2018, the medical records of 61 patients (84 ureters; CMS, 39 patients, 54 ureters; DJS, 22 patients, 30 ureters) with MUO caused by AGC were reviewed retrospectively. The Kaplan-Meier method and log-rank test were used to evaluate differences of primary or assisted primary patency between groups. Cox regression was conducted separately for early (within 7 days) and late (after 7 days) primary patency. RESULTS: Technical success of CMS placement was 100% (54/54) and 96.8% (29/30) for DJS (p=0.357). The cumulative stent patency rates at 1, 3, 6, and 12 months were 77%, 74%, 70%, and 70%, in the CMS group and 72%, 60%, 53%, and 26%, in the DJS group. Apart from the period within 7 days (p=0.784), primary patency was consistently higher in the CMS group when compared to the DJS group over the entire follow-up period (p=0.034). Assisted primary patency was consistently higher in the CMS group than in the DJS group over the entire follow-up period (p=0.001). The CMS group was more likely to have complications than the DJS group (48.1% versus 16.7%, p=0.004). Complications were minor, self-limiting events such as haematuria/haematoma. CONCLUSION: CMS had better late patency and assisted primary patency than DJS. Procedure-related minor complications more frequently occurred with CMS.

[Urinary retinol binding protein and ß2-microglobulin were associated with urinary albumin to creatinine ratio and renal function in hospitalized diabetic patients].

Objective: To explore the associations of urinary retinol binding protein (RBP) and ß2-microglobulin (ß2-MG) with urinary albumin to creatinine ratio (UACR) and renal function in hospitalized patients with type 2 diabetes mellitus (T2DM). Methods: A total of 1 030 Chinese patients with T2DM were included in this study. The subjects were divided into the UACR normal group (<30 mg/g), microalbuminuria group (30-300 mg/g) and macroalbuminuria group (>300 mg/g). Patients with normal UACR were further divided into two groups according to the estimated glomerular filtration rate (eGFR): the eGFR low group (<90 ml·min-1·1.73m-2) and the normal eGFR group (≥90 ml·min-1·1.73m-2). Urine RBP and ß2-MG levels among the groups were compared. Multiple linear regression analyses were applied to evaluate risk factors of urine RBP and ß2-MG. Results: In all patients (n=1 030), urine RBP and ß2-MG increased gradually with the increase of UACR across the three groups, the proportions of abnormal urine RBP (>0.7 mg/L) and ß2-MG (>370 µg/L) in these groups were 3.8%, 8.5%, 39.0% (P<0.001), and 12.9%, 26.7%, 46.8% (P<0.001), respectively. In the UACR normal group (n=788), 12.2% of the patients were with eGFR<90 ml·min-1·1.73m-2. The proportion of abnormal ß2-MG (>370 µg/L) was higher in the eGFR low group than that in the eGFR normal group (29.2% vs. 10.7%, P<0.001). Multivariate linear stepwise regression analyses were performed using natural logarithm of urine RBP or ß2-MG as dependent variable, and showed that urine RBP was independently associated with UACR (ß=0.0005, P<0.001), serum creatinine (ß=0.006, P<0.001) and glycosylated hemoglobin A1c (ß=0.050, P=0.001), and ß2-MG was independently correlated with UACR (ß=0.000 4, P<0.001), serum creatinine (ß=0.011, P<0.001), systolic blood pressure (ß=0.005, P=0.031) and fasting blood-glucose (ß=0.027, P=0.046). Conclusions: Urine RBP and ß2-MG are positively associated with high UACR and impaired renal function in T2DM patients, and these changes could occur before UACR and eGFR turned out to be abnormal. It is recommended that urine RBP and ß2-MG be detected as early as possible to identify diabetic kidney disease in patients with normal UACR and eGFR.

[Studying the correlation between ferritin and non-alcoholic fatty liver disease].

Objective: To analyze the correlation between serum ferritin and steatosis in non-alcoholic fatty liver disease. Methods: Data of 167 cases who underwent liver biopsy in the Affiliated Hospital of Hangzhou Normal University were collected. Hydrogen proton magnetic resonance spectroscopy were performed within one week. The pathological results of liver biopsy were used as the gold standard to analyze the case data, serological indicators, magnetic resonance spectroscopy-proton density fat fraction. Results: Pathological monitoring result showed that the serum ferritin in patients without steatosis, and with mild, moderate and severe steatosis were (206.20 ± 189.83), (286.65 ± 200.80), (326.55 ± 214.71), (391.50 ± 184.93) ng/ml, respectively, P < 0.005. Serum ferritin was correlated to body mass index, PDFF, alanine aminotransferase, gamma glutamyltransferase, low-density lipoprotein, high-density lipoprotein. The area under ​​the receiver operating characteristic curve with ferritin for the diagnosis of non-alcoholic fatty liver disease was 0.716, and the optimal diagnostic threshold was 214.56 ng/ml. The sensitivity and specificity were 80.1%, and 68.8%, respectively. There was no statistically significant difference between the intralobular inflammation, fibrosis, and ferritin. Prussian blue iron staining had no apparent deposition of iron particles. Conclusion: Ferritin has significant positive correlation with the results of pathological and magnetic resonance imaging for liver steatosis. Therefore, it can be used as a non-invasive diagnostic method for liver steatosis evaluation.

[Study of liver fat and iron deposition quantification based on magnetic resonance imaging in rats with nonalcoholic fatty liver disease].

Objective: To investigate the accuracy of magnetic resonance imaging (MRI) for quantitative determination of liver fat and iron content through a rat model of non-alcoholic fatty liver disease (NAFLD) induced by methionine-choline deficient (MCD) diet. Methods: Sixty SD rats were randomly divided into experimental (MCD-diet group, n = 30) and normal control group (normal diet, n = 30). Rats were subjected to special MRI examinations at the ends of 2, 4, and 8 weeks. Proton density fat fraction (PDFF) and R2* value were obtained, and then the rats were sacrificed. The liver tissues were stained with HE, Prussian blue, etc. Liver tissue non-heme iron (NHI) homogenate was determined by flame atomic absorption spectrometry. According to different data, one-way analysis of variance, t-test or χ (2) test was used for statistical analysis. Results: PDFF and R2 * values in the MCD diet group at 2, 4 and 8 weeks were 23.37% ± 9.20%, 28.07% ± 6.84%, 25.40% ± 7.04% (P < 0.01) and 90.58 ± 15.92, 104.12 ± 13.47, 106.35 ± 15.76 (P < 0.05), respectively, which were significantly higher than the normal control group PDFF (2.39% ± 0.50%, 2.45% ± 0.45%, 3.26% ± 0.80%) and R2* (48.93 ± 7.90, 54.71 ± 5.91, 64.25 ± 15.76). Additionally, with the disease progression, R2 * had gradually increased, which was consistent with the NHI trend in liver tissue homogenates of each group. Conclusion: MRI, as a non-invasive quantitative method, can accurately assess liver fat and iron content in fatty liver disease, and with the degree of severity of fat changes, iron deposits tend to increase.

[Recommendations for public health protection against flood disaster].

Flood disaster is one of the most serious natural disasters in the world, and it could pose an inestimable impact on the affected people. Based on existing laws, regulations, and emergency manuals in China, extensive literature review, epidemiological and related protection evidence, and expert consultation, this study analyzed different health risk factors of flood disaster and proposed a multi-stage, multi-population, and multi-phase comprehensive protection measures for the public in the perspective of pre-event prevention, in-event intervention and post-event rescue strategy, which could provide a scientific basis for improving the level of public health protection against the flood disaster and corresponding health outcomes.

Antibacterial activity against Ralstonia solanacearum of the lipopeptides secreted from the Bacillus amyloliquefaciens strain FJAT-2349.

AIMS: The aims of this study were to identify the structure of antibacterial lipopeptide (LP) produced by Bacillus amyloliquefaciens strain FJAT-2349, to analyse the effects of the culture medium and temperature on LP production and to assess the biocontrol efficiency of the LPs against tomato bacterial wilt. METHODS AND RESULTS: Lipopeptides were extracted by acid precipitation and resolved in methanol and their structure was identified through LC-QTOF-MS/MS method. The antibacterial activities of the LPs were evaluated through inhibition zone experiments. The biocontrol efficiency of the LPs against tomato bacterial wilt was examined by a pot test. The LPs were composed of iturin (C14 -C17 iturin A), fengycin (C14 /C16 fengycin A, C14 fengycin B2 , C16 fengycin A2 /B2 , C16 -C17 fengycin B, C15 fengycin A derivatives and C15 fengycin B derivatives) and surfactin (C12 -C16 surfactin A). Moreover, the composition of the LPs was significantly influenced by the culture medium and temperature; the contents of iturin, fengycin and surfactin varied within the range from 0·41-5·89, 4·54-181·67 and 2·05-19·65 mg l-1 in the different culture media and from 0·39-11·04, 1·45-215·14 and 7·79-24·43 mg l-1 under different culture temperatures respectively. The results indicated that the contents of the LP mixture, fengycin and surfactin secreted from FJAT-2349 all decreased along with an increasing culture temperature. The fermentation supernatants and LP extracts had the strongest inhibition activities of Ralstonia solanacearum when strain FJAT-2349 was incubated at 25°C using potato dextrose broth as the culture medium among all the assayed culture conditions. The purified fengycin was found to be the active antibacterial compound against R. solanacearum, but the purified surfactin was not. The pot experiments demonstrated that the LPs secreted from the strain FJAT-2349 could effectively control the tomato bacterial wilt with a biocontrol efficiency of 97·6%. CONCLUSIONS: The LPs secreted from strain FJAT-2349 could serve as potential biocontrol agents against tomato bacterial wilt. SIGNIFICANCE AND IMPACT OF THE STUDY: The LPs exhibited good potential applications in the biocontrol of tomato bacterial wilt.

[Study on the correlation between small intestinal dendritic cells and non-alcoholic fatty liver disease in mice].

Objective: To preliminary, explore the effect of small intestinal epithelial dendritic cells on the occurrence and development of nonalcoholic fatty liver disease in mice. Methods: Thirty-two (half male and half female) 4-week-old C57BL/6 mice were randomly divided into two groups. The mice were fed with normal diet (SD group) and high-fat diet (HFD group). Eight mice (half male and half female) were randomly killed from each group over the 14 and 20-weeks feeding period to observe their body weight, liver and small-intestine wet weight. Alanine aminotransferase, aspartate aminotransferase, blood glucose, high-density lipoprotein, low-density lipoprotein, total cholesterol and triglyceride were determined by eyeball blood samples. Pathological diagnosis and alcoholic fatty liver disease activity score were collected. The number of mice small intestinal dendritic cells was observed under a microscope. Statistical analysis was performed to compare two groups of independent samples with homogeneity test of variance, t test, and covariance analysis. Results: The body weight, liver wet weight, serum alanine aminotransferase and aspartate aminotransferase of mice in HFD group were significantly higher than those of control group at 20 weeks (P < 0.05), and the serum high density lipoprotein of mice in HFD group was significantly higher than that of SD group at 14 weeks (P < 0.05). At 14th weeks, the liver tissue of mice in HFD group had early pathological manifestations of hepatitis (fatty degeneration, punctate necrosis and balloon-like degeneration). Of which 87.5% (7/8) of them were diagnosed as non-alcoholic steatohepatitis or non-alcoholic fatty liver disease, while only a few mice in SD group had early pathological manifestations of hepatitis. At 20th weeks, all mice in HFD group were diagnosed with non-alcoholic steatohepatitis or non-alcoholic fatty liver disease, while none of the mice in SD group was diagnosed with non-alcoholic fatty liver disease. At both time points, the percentage of small intestinal dendritic cells in HFD group was significantly higher than that in SD group (14 weeks: 4.181 ± 4.314 vs. 15.099 ± 10.349; 20 weeks: 9.615 ± 8.267 vs. 32.839 ± 24.475, both P < 0.05). Statistical analysis combined with the alcoholic fatty liver disease activity score showed that there was no linear correlation between the two groups (regression coefficient was 20.196%). Conclusion: The number and different staging of small intestinal dendritic cells in mice is associated with the occurrence and development of NAFLD.

Recombinant ApxIV protein enhances protective efficacy against Actinobacillus pleuropneumoniae in mice and pigs.

AIMS: Available bacterins, commercial or autogenous, for Actinobacillus pleuropneumoniae disease control have, thus far, shown debatable protective efficacy and only in homologous challenges. Our study sought to determine whether the addition of reombinant protein ApxIV to the multicomponent vaccine could enhance protection against homologous and heterologous challenge of A. pleuropneumoniae. METHODS AND RESULTS: The virulence of ApxI, ApxII, ApxIV and OMP were cloned and expressed using a prokaryotic system; these recombinant proteins were combined with inactivated A. pleuropneumoniae serovar 1 to formulate different multicomponent vaccines. Immune response and protective efficacy of the vaccines were evaluated in mice and pigs. A protection rate of 67% was observed against heterologous challenge in mice vaccinated with the rApxIV formulation. Piglets vaccinated with vaccine containing ApxIV produced significantly higher antibody titre and provided complete protection and reduced gross lesions by 67% when compared with the nonimmunized group after homologous challenge. Additionally, flow cytometry analysis showed significant cellular immune response. CONCLUSIONS: The results of our vaccination experiments revealed that a combination of inactivated bacteria and the recombinant antigens rApxI, rApxII, rApxIV and rOMP can provide effective protection against heterologous A. pleuropneumoniae challenge. SIGNIFICANCE AND IMPACT OF THE STUDY: The addition of ApxIV to the multicomponent vaccine could enhance homologous and heterologous protection in mice and pigs, respectively, against challenge by A. pleuropneumoniae.

[Anthropometry and the risk of colorectal cancer in males: a prospective cohort study].

Objective: To investigate the association between anthropometry and colorectal cancer risk in Chinese males. Methods: Anthropometry and incident colorectal cancer cases were collected on a biennial basis starting in May 2006 among males in Kailuan Cohort (2006-2014). In addition, electronic database of hospitals affiliated to Kailuan Community, Insurance System of Kailuan Community and Tangshan were also searched for supplementary information. Cox proportional hazards regression models and linear models were used to evaluate the association between baseline anthropometry and the risk of colorectal cancer in males. Results: A total of 106 786 males were included and 318 new colorectal cancer cases were identified in the Kailuan male cohort study, with 747 337.60 person-years follow-up by 31 December 2014. The median follow-up time was 7.90 years. Highest quartile waist circumference (≥94.0 cm) or WHtR (≥0.55) had 1.45 (95%CI: 1.05-2.02) and 1.66 (95%CI: 1.15-2.41) higher risk of colorectal cancer when compared with lowest waist circumference (<82.0 cm) or WHtR (<0.48) after adjusting for age, education, smoking, alcohol drinking, sitting time and dust exposure. Subgroup analyses by site indicated that males with BMI ≥26.27 kg/m(2), waist circumference ≥94.0 cm or WHtR ≥0.55 had HRs (95%CI) of 2.18(1.27-3.73), 2.20 (1.27-3.78) and 2.42 (1.29-4.56) for colon cancer risk, respectively. Linear models showed the HR of colon cancer and 95%CI would be 1.59 (1.24-2.02) with every 0.1 growth in WHtR. Conclusion: Obesity may be responsible for an increased risk of colorectal cancer in male. Reasonable weight control may be one of the effective measures to prevent colorectal cancer.

Involvement of tau phosphorylation in traumatic brain injury patients.

OBJECTIVES: Traumatic brain injury (TBI) results in significant morbidity and mortality throughout the world. In TBI patients suffering cognitive, emotional, and behavioral deficits, the leading cause derives from the physical injury to the central nervous system (CNS) that impairs brain function. MATERIALS AND METHODS: Here, we applied a targeted approach to understand the potential mechanisms of neuron damage after TBI. Tau protein phosphorylation was compared in the brain tissues collected from patients underwent brain surgery based on the assessment of brain injury extent by Glasgow Coma Scale (GCS). RESULTS: The results indicated that the levels of phosphorylated tau were significantly higher in the severe and extremely severe TBI groups, compared to the moderate group of patients. Phosphorylated, but not the total tau protein was uniquely correlated with the GCS score (R2 =.7849, P<.01) in 142 TBI patients. Consistently, the activities of key players associated with tau hyperphosphorylation GSK-3ß and PP2A showed parallel correlations with the severity of TBI as well. CONCLUSION: These data suggest that the enhanced tau protein phosphorylation occurs upon severe neuron injures and may contribute to the pathological structural changes of CNS leading to brain damage of TBI.

[Effectiveness of tyrosine kinase inhibitors against non-small cell lung cancer patients with postoperative recurrence harboring uncommon EGFR mutations].

Objective: To investigate the efficacy of tyrosine kinase inhibitor (TKI) treatment on non-small cell lung cancer (NSCLC) patients with postoperative recurrence who harbored uncommon EGFR mutations, and discuss the relationship between TKI treatment and prognosis. Methods: A total of 39 relapsed NSCLC patients after surgery with EGFR uncommon mutations who were detected at Cancer Hospital, Chinese Academy of Medical Sciences between January 1999 and December 2013 were retrospectively analyzed in this study. Twenty patients were treated with EGFR-TKI after recurrence and 19 cases were not. The clinical characteristics of patients with EGFR uncommon mutations were evaluated, and the prognosis of TKI-treatment group and non-TKI treatment group was compared. Results: In 39 relapsed NSCLC patients with EGFR uncommon mutations, insertion mutations and point mutations were included. The highest frequency of EGFR uncommon mutation happened in exon 20 (20/39, 51.3%). A total of 13 uncommon point mutations were detected in exon 18, 20 and 21. The most frequent rare point mutations located in exon 21, and there were 7 different point mutation sites in exon 21. G719S/C/A mutation in exon 18 was the most common type of point mutation (14/25, 56.0%). Survival after postoperative recurrence in TKI treatment group was obviously better than that in non-TKI treatment group, the median time after recurrence were 44 months and 23 months, respectively (P=0.044). However, the postoperative overall survival showed no differences between two groups (48 months vs 43 months, P=0.129). Conclusion: NSCLC patients with postoperative recurrence who harbored rare EGFR mutations should be treated with TKI agent.

[Relationship between inflammatory markers and the risk of colorectal cancer in Kailuan male cohort].

Objective: To investigate whether elevated levels of high sensitivity C-Reactive Protein (hsCRP) and neutrophil (NE) at baseline are associated with an increased risk of colorectal cancer in Kailuan male cohort. Methods: Since May 2006, males from Kailuan cohort were included in this study. Information on demographics, medical history, anthropometry, hsCRP and NE were collectedat baseline for all subjects. Multivariable Cox proportional hazards regression models were used to calculate hazard ratios (HR) of association between baseline hsCRP and NE and colorectal cancer risk. Results: By December 31, 2015, a total of 73 869 participants were enrolled in this study. During the follow-up, 336 incident colorectal cancer cases were identified. All participants were divided into three groups according to the level of hsCRP (<1 mg/L, 1-3 mg/L and >3 mg/L). The cumulative incidence of colorectal cancer were 456/10(5,) 510/10(5) and 746/10(5) in these 3 groups, respectively (χ(2)=10.79, P=0.005). Compared with participants with lower hsCRP levels (<1 mg/L), individuals with the highest hsCRP (>3 mg/L) levels had significant increased risks of colorectal cancer (HR=1.38, 95%CI: 1.05-1.81, P=0.020)after adjusting for age, gender, smoking, drinking, BMI, diabetes and income. Furthermore, subjects were divided into two groups according to the level of NE (≤ 4.08×10(9)/L and > 4.08×10(9)/L). Multivariable Cox proportional hazards regression models indicated that there is no statistical significance of association between NE and colorectal cancer. Conclusions: Elevated levels of hsCRP at baseline might increase the risk of colorectal cancer in males.

[Sivelestat alleviates nonalcoholic steatohepatitis in mice through inhibiting activation of Kupffer cells].

Objective: To investigate the role of neutrophil elastase inhibitor, sivelestat, in preventing and treating nonalcoholic steatohepatitis (NASH) and its underling mechanisms. Methods: A total of forty 4-week-old male C57BL/6J ApoE-/-mice were equally divided into the following four groups: standard chow (SC)+isotonic saline; SC+sivelestat; high-fat, high-cholesterol (HFHC) diet+isotonic saline; and HFHC+sivelestat. These mice were treated with above methods for 12 weeks. Blood and liver tissue samples were collected to measure biochemical parameters, hepatic steatosis and non-alcoholic fatty liver disease (NAFLD) activity score (inflammation) were evaluated by oil red O staining and HE staining, respectively. The mRNA and protein expression levels of hepatic inflammatory cytokines, CD68, and F4/80 were determined by quantitative RT-PCR and immunohistochemistry, respectively. Comparison of means between the four groups was made by one-way analysis of variance, and comparison between any two groups was made by the LSD or SNK method (for data with homogeneity of variance) or the Tamhane or Dunnett method (for data with heterogeneity of variance). Results: Mice fed with an HFHC diet for 12 weeks developed typical pathological features of NASH compared with those fed with SC. Compared with mice fed with HFHC diet without sivelestat, those treated with HFHC and sivelestat exhibited the following features: (1) significantly reduced fast blood glucose, blood cholesterol, and hepatic biochemical parameters, as well as increased insulin sensitivity; (2) significantly reduced NAFLD activity score (5.71±1.11 vs 3.16±1.16, P < 0.05); (3) reduced monocyte chemoattractant protein-1 and tumor necrosis factor -α; (4) significantly reduced mRNA levels of CD68 and F4/80; and (5) reduced expression of CD68 in the liver. Conclusion: Sivelestat alleviates the hepatic steatosis and inflammation of NASH in mice by inhibiting the activation of Kupffer cells.

Mitochondrial tRNALeu(CUN) A12307G variant may not be associated pancreatic cancer.

Mitochondrial DNA mutations that lead to mitochondrial dysfunction have long been proposed to play important roles in the development of pancreatic cancer. Of these, alterations to mitochondrial tRNA genes constitute the largest group. Most recently, a variation at position 12307 in the gene encoding tRNA(Leu(CUN)) has been reported to be associated with this disease. However, the molecular mechanism underlying this relationship remains poorly understood. To assess this association, we evaluated this variant by evolutionary conservation analysis, measurements of allelic frequencies among control subjects, and use of several bioinformatic tools to estimate potential structural and functional alterations. We found this residue to have a high conservation index; however, the presence of the A12307G variation in control subjects revealed by a literature search suggested it to be common in human populations. Moreover, RNAfold results showed that this variant did not alter the secondary structure of tRNA(Leu(CUN)). Through the application of a pathogenicity scoring system, this variant was determined to be a "neutral polymorphism," with a score of only 4 points based on current data. Thus, the contribution of the A12307G variant to pancreatic cancer needs to be addressed in further experimental studies.