[Evaluation of the efficacy and safety of Nocardia rubra cell wall skeleton immunotherapy for cervical high-risk HPV persistent infection].

Objective: To evaluate the efficacy and safety of Nocardia rubra cell wall skeleton (Nr-CWS) in the treatment of persistent cervical high-risk human papillomavirus (HR-HPV) infection. Methods: A randomized, double blind, multi-center trial was conducted. A total of 688 patients with clinically and pathologically confirmed HR-HPV infection of the cervix diagnosed in 13 hispital nationwide were recruited and divided into: (1) patients with simple HR-HPV infection lasting for 12 months or more; (2) patients with cervical intraepithelial neoplasia (CIN) Ⅰ and HR-HPV infection lasting for 12 months or more; (3) patients with the same HR-HPV subtype with no CINⅡ and more lesions after treatment with CINⅡ or CIN Ⅲ (CINⅡ/CIN Ⅲ). All participants were randomly divided into the test group and the control group at a ratio of 2∶1. The test group was locally treated with Nr-CWS freeze-dried powder and the control group was treated with freeze-dried powder without Nr-CWS. The efficacy and negative conversion rate of various subtypes of HR-HPV were evaluated at 1, 4, 8, and 12 months after treatment. The safety indicators of initial diagnosis and treatment were observed. Results: (1) This study included 555 patients with HR-HPV infection in the cervix (included 368 in the test group and 187 in the control group), with an age of (44.1±10.0) years. The baseline characteristics of the two groups of subjects, including age, proportion of Han people, weight, composition of HR-HPV subtypes, and proportion of each subgroup, were compared with no statistically significant differences (all P>0.05). (2) After 12 months of treatment, the effective rates of the test group and the control group were 91.0% (335/368) and 44.9% (84/187), respectively. The difference between the two groups was statistically significant (χ2=142.520, P<0.001). After 12 months of treatment, the negative conversion rates of HPV 16, 18, 52, and 58 infection in the test group were 79.2% (84/106), 73.3% (22/30), 83.1% (54/65), and 77.4% (48/62), respectively. The control group were 21.6% (11/51), 1/9, 35.1% (13/37), and 20.0% (8/40), respectively. The differences between the two groups were statistically significant (all P<0.001). (3) There were no statistically significant differences in vital signs (body weight, body temperature, respiration, pulse rate, systolic blood pressure, diastolic blood pressure, etc.) and laboratory routine indicators (blood cell analysis, urine routine examination) between the test group and the control group before treatment and at 1, 4, 8, and 12 months after treatment (all P>0.05); there was no statistically significant difference in the incidence of adverse reactions related to the investigational drug between the two groups of subjects [8.7% (32/368) vs 8.0% (15/187), respectively; χ2=0.073, P=0.787]. Conclusion: External use of Nr-CWS has good efficacy and safety in the treatment of high-risk HPV persistent infection in the cervix.

[Clinical significance of ultrasound combined with serological indexes for predicting nonalcoholic fatty liver disease in patients with chronic hepatitis B with normal or slightly elevated alanine aminotransferase].

Objective: To investigate and establish the related factors of non-invasive score model for prediction of non-alcoholic fatty liver disease in chronic hepatitis B patients with normal or mildly elevated alanine aminotransferase (ALT). Methods: A total of 128 cases with chronic hepatitis B who had undergone liver biopsy were included. According to the presence or absence of hepatocyte steatosis on the pathological results of liver biopsy, they were divided into a fatty infiltration and a non-fatty infiltration group. Patients' demographic characteristics, laboratory test indexes, and pathological test results were collected. Univariate and multivariate logistic regression analysis combined with clinical screening variables were used to establish a predictive model. The prediction efficiency of the new model was evaluated by the receiver operating curve, and the difference between the accuracy of the new model and ultrasound in the diagnosis of fatty liver was compared by Delong's-test. Result: Multivariate regression analysis showed that serum triglyceride, serum uric acid and platelets were highly correlated with intrahepatic steatosis (P<0.05). The regression equation triglyceride-uric acid-platelet (TUP)-1=-8.195+0.011×uric acid+1.439×triglyceride+0.012×platelet count was established by combining the above variables. Tthe equation TUP-2=-7.527+0.010×uric acid+1.309×triglyceride+0.012×platelet count+1.397×fatty liver (ultrasound) was established (yes=1; no=0) after incorporating the results of abdominal ultrasound. The diagnostic value of TUP-1 and TUP-2 models for fatty liver was better than that of ultrasound alone and there was no statistically significant difference in diagnostic value between TUP-1 and TUP-2 models (Z=1.453, P=0.146). Conclusion: Compared with abdominal ultrasonography alone, the new model is more effective in diagnosing fatty liver and has good application value.

[Effects of curcumin on neurobehavior and oxidative stress in hippocampus of rats exposed to manganese].

Objective: To establish the animal model of subchronic manganism, and to explore the effect of manganese on neurofunction of rats and the protective effect of curcumin on neurotoxicity of manganism rats. Methods: From July to December 2019, 80 SPF male SD rats were divided into 8 groups according to body weight by random number table method, which were blank control group, low, middle and high dose manganese exposure group, low, middle and high dose curcumin antagonistic group and curcumin group, with 10 rats in each group. The low, middle and high dose manganese groups were given intraperitoneal injection of 5 mg/kg, 10 mg/kg and 15 mg/kg MnCl(2)·4H(2)O respectively. The low, middle and high dose curcumin antagonistic groups were given 100 mg/kg, 200 mg/kg and 400 mg/kg curcumin orally along with 15 mg/kg MnCl(2)·4H(2)O intraperitoneal injection. Curcumin group was given 400 mg/kg curcumin orally. The rats were exposed to 5 days a week, once a day for 16 weeks. After exposure, neurobehavioral tests (balance beam test, Morris water maze, passive avoidance test) were carried out in each group. Hippocampus tissues were taken for pathological examination and oxidative stress indexes were detected. Results: The balance beam test results showed that, compared with the blank control group, the scores of balance beam of the rats in the middle and high dose manganese exposure groups increased (P<0.05) . Compared with the high dose manganese exposure group, the balance beam scores of the low, middle and high dose curcumin antagonistic groups were decreased (P<0.05) .The results of Morris water maze showed that, compared with the blank control group, the escape latency of middle and high dose manganese exposure groups was prolonged from the third day (P<0.05) , and the average number of crossing the platform area of each manganese exposure group was decreased (P<0.05) .Compared with the high dose manganese exposure group, the escape latency of the middle and high dose curcumin antagonistic groups was shortened (P<0.05) , and the average number of crossing the original platform was increased (P<0.05) . The results of passive avoidance test show that, compared with the blank control group, the number of errors were increased in middle and high dose manganese exposure groups (P<0.05) . Compared with the high dose manganese exposure group, the number of errors in the passive avoidance test in the middle and high dose curcumin antagonistic groups were decreased (P<0.05) . Pathological examination showed that the rats treated with manganses had different degrees of degeneration and necrosis of nerve cells, and the structure of nerve cells was blurred and the number of nerve cells decreased. The above phenomena were improved after curcumin antagonism. The results of oxidative stress index showed that, compared with blank control group, the activity of superoxide dismutase (SOD) decreased and the content of malondialdehyde (MDA) increased in the hippocampus of rats exposed to middle and high dose of manganese (P<0.05) . Compared with the high dose manganese exposure group, the SOD activity increased and the MDA content decreased in the middle and high dose antagonist group (P<0.05) . Conclusion: Subchronic manganese exposure can reduce the balance function, learning and memory ability of rats, and damage the hippocampal nerve cells in oxidative stress state. Curcumin can improve the balance function and learning and memory ability of rats with manganese poisoning, improve the hippocampal nerve damage caused by manganese exposure, and has a certain protective effect on manganese induced neurotoxicity.

[Mutational analysis of ATP7B gene of hepatolenticular degeneration in Xinjiang region].

Objective: To understand the mutational characteristics of ATP7B gene of hepatolenticular degeneration in Xinjiang region. Methods: 24 cases were diagnosed as hepatolenticular degeneration and the exon of ATP7B gene was detected in some of their siblings and parents. Results: A total of 45 ATP7B gene mutations (93.75%) were detected in 24 cases, of which 14 cases were homozygous mutations or compound heterozygous mutations, six cases were heterozygous mutations and four cases were no mutations. A total of 24 gene mutations and 14 SNPS were detected, including 8 new mutations: c.251C > A, c.121A > c, c.2945C > A, c.2194C > T, c.2947T > c, c.3626T > A, c.3662_3664del, c.3557G > T. The most common mutations were c.2621C > T (p.A874V) [16.7% (4/24)] and c.2333G > T (p.R778L) [12.5% ​​(3/24)]. A total of 4 cases were diagnosed as pre-symptomatic. Conclusion: In this study, the most common mutation in the ATP7B gene is A874V. The most common genetic mutations in Han and Uyghur patients were different. The most common mutation in Han and Uyghur patients is R778L and A874V. Exon 11 is the gene mutations hot spot for patients with hepatolenticular degeneration in Xinjiang region, and is one of the priority exons to be detected when screening patients with suspected hepatolenticular degeneration.

Serum hepatitis B surface antigen correlates with fibrosis and necroinflammation: A multicentre perspective in China.

The kinetics of serum hepatitis B surface antigen (HBsAg) during the natural history of hepatitis B virus (HBV) infection has been studied, but the factors affecting them remain unclear. We aimed to investigate the factors affecting HBsAg titres, using data from multicentre, large-sized clinical trials in China. The baseline data of 1795 patients in 3 multicentre trials were studied, and the patients were classified into 3 groups: hepatitis B early antigen (HBeAg)-positive chronic HBV infection (n = 588), HBeAg-positive chronic hepatitis B (n = 596), and HBeAg-negative chronic hepatitis B (n = 611). HBsAg titres in the different phases were compared, and multiple linear progression analyses were performed to investigate the implicated factors. HBsAg titres varied significantly in different phases (P = .000), with the highest (4.60 log10 IU/mL [10%-90% confidence interval: 3.52 log10 IU/mL-4.99 log10 IU/mL]) in patients with HBeAg-positive chronic HBV infection. In all phases, age and HBV DNA were correlated with serum HBsAg level. In HBeAg-positive chronic hepatitis B patients, a negative correlation between HBsAg titres and fibrosis stage was observed. Alanine amonitransferase or necroinflammatory activity was also correlated with HBsAg titres in HBeAg-negative chronic hepatitis B patients. In conclusion, decreased HBsAg titres may be associated with advancing fibrosis in HBeAg-positive chronic hepatitis B patients or increased necroinflammation in those with HBeAg-negative chronic hepatitis B. Our findings may help clinicians better understand the kinetics of HBsAg and provide useful insights into the management of this disease.

Alpha1,2-fucosyl transferase gene, the key enzyme of Lewis y synthesis, promotes Taxol resistance of ovarian carcinoma through apoptosis-related proteins.

We aimed to investigate the role of FUT1 gene in Taxol resistance and to explore its mechanism in epithelial ovarian cancer. Three ovarian cancer cell lines, ES-2, SK-OV-3 and OVCAR-3 were selected from epithelial ovarian cancer in this experiment. Western blot was used to validate the protein expression level of FUT1 and the apoptosis proteins. The expression level of the corresponding carrier was validated by RT-PCR. Transfection and isolation of stable transfectants were carried out to establish the cell line models. The different concentrations of Taxol on the inhibition of cell growth rate was measured by MTT, in which Taxol resistance profiling in ovarian cancer cells was determined by IC50 data. Flow cytometry was conducted to compare cell apoptosis ability. Caspase-3 activity and the apoptosis proteins were measured by colorimetry and western blot, respectively, to further compare the cell apoptosis ability in different groups. To demonstrate the inhibition of miR-FUT1 combined with Taxol therapy against ovarian cancer, xenograft assay was carried out for the in vivo effect. The western blot results indicate that FUT1 is expressed in all of the ovarian cancer cells with different expression level: ES-2 > SK-OV-3 > OVCAR-3. Besides, FUT1 siRNA was used in the maximum expression of FUT1 cell line ES-2, or over-expression plasmid was used in the minimum expression of FUT1 cell line OVCAR-3, to establish stable expression cell lines. After the treatment with Taxol, the inhibition rate of Taxol was obviously decreased with the established cell model above, and the IC50 level was significantly increased in the FUT1 over-expression + Taxol group (p Keywords: FUT1, Lewis y, Taxol resistance, ovarian cancer, apoptosis.

Anti-listeria effects of chitosan-coated nisin-silica liposome on Cheddar cheese.

Listeria monocytogenes poses an increasing challenge to cheese production. To minimize the risk of bacterial contamination, a chitosan-coated nisin-silica liposome was engineered for the present study. We investigated the characteristics of nisin-silica liposomes and the anti-listeria effects of a chitosan-coated nisin-silica liposome on Cheddar cheese. The encapsulation efficiency of nisin in a liposome was sharply increased after it was adsorbed on a silica particle surface. Chitosan-coated nisin-silica liposomes displayed sustained antibacterial activity against L. monocytogenes, without affecting the sensory properties of the cheese. Chitosan-coated nisin-silica liposomes could be a promising active antimicrobial for cheese preservation.

Initial periodontal therapy for the treatment of gingival pregnancy tumor.

The purpose of this study was to evaluate the clinical efficacy of initial periodontal therapy in gingival pregnancy tumors. Thirty-nine patients diagnosed with gingival tumors of pregnancy between 2007 and 2015 were enrolled in this study. The patients received initial periodontal therapy, then supportive periodontal therapies at 3- to 6-month intervals. The patients underwent follow up for 6 months to 8 years after treatment. After plaque control, supragingival scaling, and root planning, the tumors in 25 patients were gradually eliminated without the necessity of surgery. In 3 patients, tumors <5 mm in size disappeared in a mean time of 3.6 months, 4 patients with tumors 5-10 mm disappeared in a time of 7.5 months, 11 patients with tumors 10-15 mm disappeared in 10.2 months, 6 patients with tumors 15-20 mm disappeared in 15 months, and one patient with a tumor >20 mm disappeared in 20 months. No recurrence of gingival pregnancy tumors was noted during subsequent follow-up. Initial periodontal therapy combined with oral hygiene maintenance is efficacious in treating gingival pregnancy tumors of patients with normal hormone levels, which can potentially serve as an option to avoid surgery.

Effects of acrylonitrile on the pathological morphology and apoptosis of neurons in rats.

This study aimed to evaluate the effects of acrylonitrile (ACN) on neuronal morphology and apoptosis in rats. An ACN solution was administered to Wistar rats by gavage at doses of 0, 5, 10, or 20 mg/kg, 5 days a week for 13 weeks. The morphology of neurons and the presence of apoptosis was examined by light and electron microscope, DNA electrophoresis, immunohistochemistry, and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling. Significant vacuolation and the widening of the interspaces around blood vessels were observed in the groups that received the highest dose. Disordered myelin sheaths, malformed neuronal nuclei, and chromatin condensation at the periphery of the nucleus that formed crescents were also observed in the treated rats. The number of apoptotic neurons was significantly decreased (P < 0.05) in the treated groups (5 mg/kg group: 1.5 ± 1.22 apoptotic neurons/slide; 10 mg/kg group: 2.5 ± 1.05 apoptotic neurons/slide; 20 mg/kg group: 2.34 ± 1.21 apoptotic neurons/slide) compared to the control group (4.5 ± 1.52 apoptotic neurons/slide). The number of Bcl-2-positive neurons and the levels of staining were increased in the treated rats compared to those of the control group. These results suggested that ACN may induce serious morphological changes in rat neurons and inhibit neuronal apoptosis in rats.

Practising case-based learning in oral medicine for dental students in China.

INTRODUCTION: Teacher-centred education dominates dental education in China. Student-centred education has recently been introduced in the School of Stomatology, Wuhan University, and the effectiveness of such methods needs to be tested. The purpose of this study is to compare the learning outcomes of case-based learning (CBL) and lecture-based education (LBE) in an oral medicine curriculum. MATERIALS AND METHODS: We chose oral leukoplakia as the learning subject for dental students. Forty fourth-year dental students participated in the study. First, they were presented to basic knowledge of oral leukoplakia and related oral mucosal diseases. Then, they were divided into a CBL group (n=20) and an LBE group (n=20) by random numbers. The groups experienced the remaining course in separate groups. All students answered a questionnaire on their satisfaction with the education and the same standardised written test to analyse their learning outcomes. RESULTS: Both CBL and LBE courses were well accepted by students according to the satisfactory scores of the questionnaire. The test scores of the CBL group (90.00±6.69) were significantly higher (P<0.01) than those of the LBE group (83.00±6.77). The percentage of high test score (test score≥85) of the CBL group (85%) was also significantly higher (P<0.01) than that of the LBE group (45%). CONCLUSIONS: In this example, CBL was found to be more effective than LBE to teach dental students. These findings suggest that CBL should be added in our future oral medicine curriculum for dental students.

Lipolysis is accompanied by immune microenvironment remodeling in adipose tissue of obesity with different exercise intensity.

OBJECTIVE: Obesity and overweight are risk factors for chronic disease worldwide. The purpose of this study was to compare the transcriptome of exercise-induced fat mobilization in obese people, and to explore the effect of different exercise intensity on the correlation of immune microenvironment remodeling and lipolysis in adipose tissue. MATERIALS AND METHODS: Microarray datasets of adipose tissue before and after exercise were downloaded from the Gene Expression Omnibus. Then, we used gene-enrichment analysis and PPI-network construction to elucidate the function and enrichment pathways of the differentially expressed genes (DEGs) and to identify the central genes. A network of protein-protein interactions was obtained using STRING and visualized with Cytoscape. RESULTS: A total of 929 DEGs were identified between 40 pre-exercise (BX) samples and 65 post-exercise (AX) samples from GSE58559, GSE116801, and GSE43471. Among these DEGs, adipose tissue-expressed genes were duly recognized. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses indicated that DEGs were mostly enriched in lipid metabolism. Studies have found that mitogen-activated protein kinase (MAPK) signaling pathway and forkhead box O (FOXO) signaling pathway are up-regulated, while Ribosome, coronavirus disease (COVID-19) and IGF-1 gene are down-regulated. Although we found the up-regulated genes that noted IL-1 among others, and the down-regulated gene was IL-34. The increase of inflammatory factors leads to changes in cellular immune microenvironment, and high-intensity exercise leads to increased expression of inflammatory factors in adipose tissue, leading to inflammatory responses. CONCLUSIONS: Exercise at different intensities leads to the degradation of adipose and is accompanied by changes in the immune microenvironment within adipose tissue. High intensity exercise can cause the imbalance of immune microenvironment of adipose tissue while causing fat degradation. Therefore, moderate intensity and below exercise is the best way for the general population to reduce fat and weight.

Comparison of cytological adequacy in ultrasound-guided fine-needle aspiration of thyroid nodules with different numbers of needle passes.

OBJECTIVE: The aim of this study was to compare the cytological adequacy rates of different needle passes in ultrasound-guided fine-needle aspiration biopsy of thyroid nodules and, thus, to help establish the criterion for selecting the number of needle passes according to the characteristics of thyroid nodules. PATIENTS AND METHODS: This single-center and randomized prospective study involved 207 consecutive patients with 240 solid or predominantly solid thyroid nodules. These nodules were randomly divided into a 1-pass group, a 2-pass group, and a 3-pass group. Then the nodules were sent for cytopathological diagnosis, and cytological results were classified according to the Bethesda classification. Bethesda I was defined as inadequate, and Bethesda Ⅱ-Ⅵ were defined as adequate. Then the cytological adequacy rates of different groups were compared. RESULTS: In total, 221 nodule specimens were considered as adequate and 19 nodule specimens inadequate. The overall adequacy rate was 92.1%. However, there were no significant differences among the 1, 2, and 3-pass groups in terms of adequacy rates (91.3%, 92.5%, and 92.5%, respectively). CONCLUSIONS: The number of needle passes does not significantly affect the cytological adequacy in ultrasound-guided fine-needle aspiration of solid or predominantly solid thyroid nodules. The cytological adequacy of one-needle pass is comparable to those of two and three-needle passes.

[Safety of double and a half layered esophagojejunal anastomosis in radical gastrectomy: A prospective, multi-center, single arm trial].

Objective: To evaluate the safety of double and a half layered esophagojejunal anastomosis in radical gastrectomy. Methods: This prospective, multi-center, single-arm study was initiated by the Affiliated Cancer Hospital of Zhengzhou University in June 2021 (CRAFT Study, NCT05282563). Participating institutions included Nanyang Central Hospital, Zhumadian Central Hospital, Luoyang Central Hospital, First Affiliated Hospital of Henan Polytechnic University, First Affiliated Hospital of Henan University, Luohe Central Hospital, the People's Hospital of Hebi, First People's Hospital of Shangqiu, Anyang Tumor Hospital, First People's Hospital of Pingdingshan, and Zhengzhou Central Hospital Affiliated to Zhengzhou University. Inclusion criteria were as follows: (1) gastric adenocarcinoma confirmed by preoperative gastroscopy;(2) preoperative imaging assessment indicated that R0 resection was feasible; (3) preoperative assessment showed no contraindications to surgery;(4) esophagojejunostomy planned during the procedure; (5) patients volunteered to participate in this study and gave their written informed consent; (6) ECOG score 0-1; and (7) ASA score I-III. Exclusion criteria were as follows: (1) history of upper abdominal surgery (except laparoscopic cholecystectomy);(2) history of gastric surgery (except endoscopic submucosal dissection and endoscopic mucosal resection); (3) pregnancy or lactation;(4) emergency surgery for gastric cancer-related complications (perforation, hemorrhage, obstruction); (5) other malignant tumors within 5 years or coexisting malignant tumors;(6) arterial embolism within 6 months, such as angina pectoris, myocardial infarction, and cerebrovascular accident; and (7) comorbidities or mental health abnormalities that could affect patients' participation in the study. Patients were eliminated from the study if: (1) radical gastrectomy could not be completed; (2) end-to-side esophagojejunal anastomosis was not performed during the procedure; or (3) esophagojejunal anastomosis reinforcement was not possible. Double and a half layered esophagojejunal anastomosis was performed as follows: (1) Open surgery: the full thickness of the anastomosis is continuously sutured, followed by embedding the seromuscular layer with barbed or 3-0 absorbable sutures. The anastomosis is sutured with an average of six to eight stitches. (2) Laparoscopic surgery: the anastomosis is strengthened by counterclockwise full-layer sutures. Once the anastomosis has been sutured to the right posterior aspect of the anastomosis, the jejunum stump is pulled to the right and the anastomosis turned over to continue to complete reinforcement of the posterior wall. The suture interval is approximately 5 mm. After completing the full-thickness suture, the anastomosis is embedded in the seromuscular layer. Relevant data of patients who had undergone radical gastrectomy in the above 12 centers from June 2021 were collected and analyzed. The primary outcome was safety (e.g., postoperative complications, and treatment). Other studied variables included details of surgery (e.g., surgery time, intraoperative bleeding), postoperative recovery (postoperative time to passing flatus and oral intake, length of hospital stay), and follow-up conditions (quality of life as assessed by Visick scores). Result: [1] From June 2021 to September 2022,457 patients were enrolled, including 355 men and 102 women of median age 60.8±10.1 years and BMI 23.7±3.2 kg/m2. The tumors were located in the upper stomach in 294 patients, mid stomach in 139; and lower stomach in 24. The surgical procedures comprised 48 proximal gastrectomies and 409 total gastrectomies. Neoadjuvant chemotherapy was administered to 85 patients. Other organs were resected in 85 patients. The maximum tumor diameter was 4.3±2.2 cm, number of excised lymph nodes 28.3±15.2, and number of positive lymph nodes five (range one to four. As to pathological stage,83 patients had Stage I disease, 128 Stage II, 237 Stage III, and nine Stage IV. [2] The studied surgery-related variables were as follows: The operation was successfully completed in all patients, 352 via a transabdominal approach, 25 via a transhiatus approach, and 80 via a transthoracoabdominal approach. The whole procedure was performed laparoscopically in 53 patients (11.6%), 189 (41.4%) underwent laparoscopic-assisted surgery, and 215 (47.0%) underwent open surgery. The median intraoperative blood loss was 200 (range, 10-1 350) mL, and the operating time 215.6±66.7 minutes. The anastomotic reinforcement time was 2 (7.3±3.9) minutes for laparoscopic-assisted surgery, 17.6±1.7 minutes for total laparoscopy, and 6.0±1.2 minutes for open surgery. [3] The studied postoperative variables were as follows: The median time to postoperative passage of flatus was 3.1±1.1 days and the postoperative gastrointestinal angiography time 6 (range, 4-13) days. The median time to postoperative oral intake was 7 (range, 2-14) days, and the postoperative hospitalization time 15.8±6.7 days. [4] The safety-related variables were as follows: In total, there were 184 (40.3%) postoperative complications. These comprised esophagojejunal anastomosis complications in 10 patients (2.2%), four (0.9%) being anastomotic leakage (including two cases of subclinical leakage and two of clinical leakage; all resolved with conservative treatment); and six patients (1.3%) with anastomotic stenosis (two who underwent endoscopic balloon dilation 21 and 46 days after surgery, the others improved after a change in diet). There was no anastomotic bleeding. Non-anastomotic complications occurred in 174 patients (38.1%). All patients attended for follow-up at least once, the median follow-up time being 10 (3-18) months. Visick grades were as follows: Class I, 89.1% (407/457); Class II, 7.9% (36/457); Class III, 2.6% (12/457); and Class IV 0.4% (2/457). Conclusion: Double and a half layered esophagojejunal anastomosis in radical gastrectomy is safe and feasible.

Universal DNA methylation age across mammalian tissues.

Aging, often considered a result of random cellular damage, can be accurately estimated using DNA methylation profiles, the foundation of pan-tissue epigenetic clocks. Here, we demonstrate the development of universal pan-mammalian clocks, using 11,754 methylation arrays from our Mammalian Methylation Consortium, which encompass 59 tissue types across 185 mammalian species. These predictive models estimate mammalian tissue age with high accuracy (r > 0.96). Age deviations correlate with human mortality risk, mouse somatotropic axis mutations and caloric restriction. We identified specific cytosines with methylation levels that change with age across numerous species. These sites, highly enriched in polycomb repressive complex 2-binding locations, are near genes implicated in mammalian development, cancer, obesity and longevity. Our findings offer new evidence suggesting that aging is evolutionarily conserved and intertwined with developmental processes across all mammals.

Widespread but small-scale changes in the structural and dynamic properties of vaccinia virus poly(A) polymerase upon association with its processivity factor in solution.

Vaccinia virus poly(A) polymerase (VP55) has been analyzed via hydrogen-deuterium exchange (HDX) mass spectrometry in the absence and presence of its processivity factor, VP39, to improve our understanding of the mechanism by which processivity is impressed on the polymerase. For 119 peptic peptides covering 74.1% of VP55, the extent of HDX at 900 s was interpreted in the context of parameters deduced from the VP55-VP39 X-ray crystal structure. While HDX exhibited a degree of correlation with the mean SASA of whole residues within each peptide segment, HDX was generally more active than expected from either the SASA or hydrogen bonding status of the exchangeable amide proton, indicating a significant molecular dynamics contribution to amide proton deprotection. Peptic peptides undergoing either more or less HDX than expected were distributed throughout VP55 and showed consistency between multiple overlapping peptides. VP39 had a net, marginal cooling effect on VP55, indicating a possible restriction of VP55's flexibility. VP39's cooling effect was most extensive within the central domain of VP55's three domains, while a patch within VP55's C-terminal domain showed an increased level of HDX in the presence of VP39. Langevin dynamics all-atom simulations of VP55 motions showed slower relaxation to equilibrium in the absence of VP39. At equilibrium, regions showing extremes of variation in simulated atomic fluctuation were localized within VP55's N- and C-terminal domains, and VP39 had a predominantly cooling effect on VP55. Broadly, across VP55's peptic peptides, a mild negative correlation was noted between the extent to which deuteration was more active than predicted from the structure and the amplitudes of the simulated atomic fluctuation and/or degree of disorder at equilibrium.

Monitoring and dynamic control of distance and tilt angle measurements in micro-alignment instrument using an imaging approach.

An accurate and simple optical triangulation method is proposed for determining the distance and the tilt angle between the window and the SQUID sensor in a scanning SQUID microscope (SSM) system. The surface of window near the sensor plane is roughened with Alumina powder so that the incident and reflected traces of the laser beam passing the window surface become visible and can be measured precisely with a normal optical microscope. Using the proposed approach, the distance between the sensor and the sample can be reproducibly adjusted to 30 microm or less. This method can also be applied to photolithography apparatus to detect the relative positions of the mask and the wafer.