Effects of cadmium chloride on testicular autophagy and blood-testis barrier integrity in prepubertal male rats / 中华劳动卫生职业病杂志

Objective: To study the effects of cadmium chloride (CdCl(2)) exposure on testicular autophagy levels and blood-testis barrier integrity in prepubertal male SD rats and testicular sertoli (TM4) cells. Methods: In July 2021, 9 4-week-old male SD rats were randomly divided into 3 groups: control group (normal saline), low dose group (1 mg/kg·bw CdCl(2)) and high dose group (2 mg/kg·bw CdCl(2)), and were exposed with CdCl(2) by intrabitoneal injection. 24 h later, HE staining was used to observe the morphological changes of testis of rats, biological tracer was used to observe the integrity of blood-testis barrier, and the expression levels of microtubule-associated protein light chain 3 (LC3) -Ⅰ and LC3-Ⅱ in testicular tissue were detected. TM4 cells were treated with 0, 2.5, 5.0 and 10.0 μmol/L CdCl(2) for 24 h to detect the toxic effect of cadmium. The cells were divided into blank group (no exposure), exposure group (10.0 μmol/L CdCl(2)), experimental group[10.0 μmol/L CdCl(2)+60.0 μmol/L 3-methyladenine (3-MA) ] and inhibitor group (60.0 μmol/L 3-MA). After 24 h of treatment, Western blot analysis was used to detect the expression levels of LC3-Ⅱ, ubiquitin binding protein p62, tight junction protein ZO-1 and adhesion junction protein N-cadherin. Results: The morphology and structure of testicular tissue in the high dose group were obvious changed, including uneven distribution of seminiferous tubules, irregular shape, thinning of seminiferous epithelium, loose structure, disordered arrangement of cells, abnormal deep staining of nuclei and vacuoles of Sertoli cells. The results of biological tracer method showed that the integrity of blood-testis barrier was damaged in the low and high dose group. Western blot results showed that compared with control group, the expression levels of LC3-Ⅱ in testicular tissue of rats in low and high dose groups were increased, the differences were statistically significant (P<0.05). Compared with the 0 μmol/L, after exposure to 5.0, 10.0 μmol/L CdCl(2), the expression levels of ZO-1 and N-cadherin in TM4 cells were significantly decreased, and the expression level of p62 and LC3-Ⅱ/LC3-Ⅰ were significantly increased, the differences were statistically significant (P<0.05). Compared with the exposure group, the relative expression level of p62 and LC3-Ⅱ/LC3-Ⅰ in TM4 cells of the experimental group were significantly decreased, while the relative expression levels of ZO-1 and N-cadherin were significantly increased, the differences were statistically significant (P<0.05) . Conclusion: The mechanism of the toxic effect of cadmium on the reproductive system of male SD rats may be related to the effect of the autophagy level of testicular tissue and the destruction of the blood-testis barrier integrity.

Analysis of the burden of disease attributable to high temperature exposure in China and globally from 1990 to 2019 / 中华劳动卫生职业病杂志

Objective: To analyze the burden of disease attributable to high temperature exposure in China and globally from 1990 to 2019, and to study the current burden of disease in relevant populations. Methods: In October 2021, based on data from the global burden of disease 2019 (GBD 2019) study, population attributable fraction (PAF), number of deaths, mortality, disability-adjusted life year (DALY) and DALY rate of Chinese and global populations with different ages and genders in 1990 and 2019 were extracted and analyzed. The rate of change was calculated, the mortality rate was normalized by the age structure of the world standard population, and the causes of disease burden caused by high temperature exposure of Chinese residents were analyzed. Results: In 2019, compared with 1990, the PAF of Chinese and global population decreased by 43.98% and 12.41% respectively, the number of deaths increased by 29.55% and 49.40% respectively, the crude mortality rate increased by 7.81% and 3.30% respectively, the DALY decreased by 48.12% and 14.41% respectively, and the DALY rate decreased by 56.82% and 40.82% respectively. The mortality rate of the ≥70 age group was higher than that of other groups. The disease burden indicators such as PAF, standardized mortality and DALY attributable to high temperature exposure in men were higher than those in women. In 2019, the main cause of DALY affected by high temperature exposure in Chinese population was ischemic heart disease (84400 person-years), and the main cause of death was ischemic heart disease (4900 cases). Conclusion: The burden of diseases attributable to high temperature exposure is still serious in China and the world at large. Targeted interventions should be formulated for men, the elderly and people with occupational exposure, and a sound surveillance system should be established to reduce the burden of diseases caused by high temperature exposure.

HbA1c comparison and diagnostic efficacy analysis of multi center different glycosylated hemoglobin detection systems / 中华预防医学杂志

Objective: Compare and analyze the results of the domestic Lanyi AH600 glycated hemoglobin analyzer and other different detection systems to understand the comparability of the detection results of different detectors, and establish the best cut point of Lanyi AH600 determination of haemoglobin A1c (HbA1c) in the diagnosis of diabetes. Methods: Multi center cohort study was adopted. The clinical laboratory departments of 18 medical institutions independently collected test samples from their respective hospitals from March to April 2022, and independently completed comparative analysis of the evaluated instrument (Lanyi AH600) and the reference instrument HbA1c. The reference instruments include four different brands of glycosylated hemoglobin meters, including Arkray, Bio-Rad, DOSOH, and Huizhong. Scatter plot was used to calculate the correlation between the results of different detection systems, and the regression equation was calculated. The consistency analysis between the results of different detection systems was evaluated by Bland Altman method. Consistency judgment principles: (1) When the 95% limits of agreement (95% LoA) of the measurement difference was within 0.4% HbA1c and the measurement score was≥80 points, the comparison consistency was good; (2) When the measurement difference of 95% LoA exceeded 0.4% HbA1c, and the measurement score was≥80 points, the comparison consistency was relatively good; (3) The measurement score was less than 80 points, the comparison consistency was poor. The difference between the results of different detection systems was tested by paired sample T test or Wilcoxon paired sign rank sum test; The best cut-off point of diabetes was analyzed by receiver operating characteristic curve (ROC). Results: The correlation coefficient R2 of results between Lanyi AH600 and the reference instrument in 16 hospitals is≥0.99; The Bland Altman consistency analysis showed that the difference of 95% LoA in Nanjing Maternity and Child Health Care Hospital in Jiangsu Province (reference instrument: Arkray HA8180) was -0.486%-0.325%, and the measurement score was 94.6 points (473/500); The difference of 95% LoA in the Tibetan Traditional Medical Hospital of TAR (reference instrument: Bio-Rad Variant II) was -0.727%-0.612%, and the measurement score was 89.8 points; The difference of 95% LoA in the People's Hospital of Chongqing Liang Jiang New Area (reference instrument: Huizhong MQ-2000PT) was -0.231%-0.461%, and the measurement score was 96.6 points; The difference of 95% LoA in the Taihe Hospital of traditional Chinese Medicine in Anhui Province (reference instrument: Huizhong MQ-2000PT) was -0.469%-0.479%, and the measurement score was 91.9 points. The other 14 hospitals, Lanyi AH600, were compared with 4 reference instrument brands, the difference of 95% LoA was less than 0.4% HbA1c, and the scores were all greater than 95 points. The results of paired sample T test or Wilcoxon paired sign rank sum test showed that there was no statistically significant difference between Lanyi AH600 and the reference instrument Arkray HA8180 (Z=1.665,P=0.096), with no statistical difference. The mean difference between the measured values of the two instruments was 0.004%. The comparison data of Lanyi AH600 and the reference instrument of all other institutions had significant differences (all P<0.001), however, it was necessary to consider whether it was within the clinical acceptable range in combination with the results of the Bland-Altman consistency analysis. The ROC curve of HbA1c detected by Lanyi AH600 in 985 patients with diabetes and 3 423 patients with non-diabetes was analyzed, the area under curve (AUC) was 0.877, the standard error was 0.007, and the 95% confidence interval 95%CI was (0.864, 0.891), which was statistically significant (P<0.001). The maximum value of Youden index was 0.634, and the corresponding HbA1c cut point was 6.235%. The sensitivity and specificity of diabetes diagnosis were 76.2% and 87.2%, respectively. Conclusion: Among the hospitals and instruments currently included in this study, among these four hospitals included Nanjing Maternity and Child Health Care Hospital in Jiangsu Province (reference instrument: Arkray HA8180), Tibetan Traditional Medical Hospital of TAR (reference instrument: Bio-Rad Variant Ⅱ), the People's Hospital of Chongqing Liang Jiang New Area (reference instrument: Huizhong MQ-2000PT), and the Taihe Hospital of traditional Chinese Medicine in Anhui Province (reference instrument: Huizhong MQ-2000PT), the comparison between Lanyi AH600 and the reference instruments showed relatively good consistency, while the other 14 hospitals involved four different brands of reference instruments: Arkray, Bio-Rad, DOSOH, and Huizhong, Lanyi AH600 had good consistency with its comparison. The best cut point of the domestic Lanyi AH600 for detecting HbA1c in the diagnosis of diabetes is 6.235%.

Taking the mechanism of glucose catabolism disorder in depression as an example to explore the research ideas and strategies of stable isotope tracer metabolomics / 药学学报

Stable isotope tracer metabolomics tracks and analyzes the whole metabolic process of the body through the tracer atoms, which belongs to the frontier technology in the field of biomedicine. This technology is of great significance and value for explaining the pathogenesis of diseases, finding biomarkers of diseases and drug action targets. Taking the mechanism of glucose catabolism disorder in depression as an example, this paper systematically expounds the stable isotope tracer metabolomics technology and its application. The research idea of stable isotope tracer metabolomics based on unmarked metabolomics was put forward, and the research strategy of biological significance interpretation from four dimensions of metabolite isotope abundance, key metabolic enzymes, metabolic flow direction and metabolite flow was given, which broke through the bottleneck of stable isotope tracer metabolomics research technology based on overall animal experiment, and provided scientific basis for the promotion and application of this technology.

Prevention and inhibition of nasopharyngeal carcinoma growth by attenuated salmonella SGN1 / 中国药理学通报

Aim To study the inhibitory effect of attenuated salmonella SGN1, overexpressing methioninase, on nasopharyngeal carcinoma (NPC) and the underlying mechanism. Methods The cell proliferation, cell cycle, cell apoptosis, clony formation and migration a-bility of 5-8F, HNE-2, CNE-2 cells were measured u-sing flow cytometry assay, clone formation assay, and wound assay after the methionine restriction treatment. 5-8F, HNE-2, CNE-2 cells were infected with SGN1 at the multiplicity of infection (MOI) of 1: 100 for 5 hours, followed with the measurement of cell growth. A xenograft model was constructed by subcutaneous injection of 5-8F cells in mice to observe the inhibitory effect of SGN1 on nasopharyngeal carcinoma. Results Compared with the control group, methionine restriction significantly inhibited the proliferation, migration ability, and clone formation of nasopharyngeal carcinoma cells and blocked the G

Effects of methionine restriction on oral cancer cell proliferation, migration and invasion / 中国药理学通报

Aim To investigate the effect of methionine restriction on the proliferation, migration and invasion of human oral squamous carcinoma CAL-27 cells. Methods Cell proliferation and colony formation ability were detected by cell counting and colony forming assay. The changes in cell cycle and apoptosis were detected by propidium iodide (PI) staining flow cytometry and Annexin V/7-amino-actinomycin staining flow cytometry. The migration and invasion ability of CAL-27 was detected by scratch and Transwell assay. The expression levels of apoptosis proteins Bax and Bcl-2, cyclins CDK2 and CDK4 and migration and invasion proteins N-cadherin and E-cadherin were examined by Western blot. Results Methionine restriction significantly inhibited the proliferation and clone formation of oral squamous cancer cell CAL-27 (P < 0. 01), induced cell cycle arrest at G

Quality of life of patients with locally advanced rectal cancer after neoadjuvant therapy and sphincter-preserving surgery / 中华胃肠外科杂志

Objective: To investigate quality of life (QoL) of patients with locally advanced rectal cancer (LARC) who underwent low anterior resection with protective stoma under neoadjuvant therapy mode, and to explore the changes of QoL of patients from before neoadjuvant therapy to 12 months after stoma reversal. Methods: A descriptive case series study was carried out. A retrospective study was performed on patients with mid and low LARC who received complete neoadjuvant long course radiotherapy and chemotherapy, followed by radical low anterior resection (LAR) combined with protective stoma at Peking Union Medical College Hospital from December 2017 to January 2020. Inclusion criteria: (1) patients with rectal MRI assessment of mT3-4b or mN1-2 without distant metastasis (M0) before neoadjuvant therapy; (2) distance from tumor lower margin to the anal verge <12 cm; (3) rectal adenocarcinoma confirmed by biopsy before neoadjuvant therapy; (4) complete cycle of neoadjuvant therapy; (5) patients undergoing radical LAR with sphincter preservation and protective ostomy; (6) patients receiving follow-up for more than 12 months after stoma reversal. Exclusion criteria: (1) patients as grade Ⅳ to Ⅴclassified by the American Society of Anesthesiologists (ASA); (2) patients with multiple primary colorectal cancer; (3) patients with history of other malignant tumors in the past 5 years; (4) patients of emergency surgery; (5) pregnant or lactating women; (6) patients with history of severe mental illness; (7) patients with contraindication of MRI, radiotherapy, chemotherapy, or surgical treatment. A total of 83 patients were enrolled, including 51 males and 28 females with median age of 59 years and mean BMI of (24.4±3.1) kg/m(2). EORTC QLQ-CR29, international erectile function index (IIEF), Wexner constipation score and low anterior resection syndrome (LARS) score were applied to investigate the QoL of the patients before neoadjuvant therapy, 3 and 12 months after ostomy reversal, including rectal anal function and sexual function. M (P25, P75) was used for the scores of the scale. Results: (1) EORTC QLQ-CR29 score showed that before neoadjuvant therapy, before surgery, 3 months and 12 months after ostomy reversal, anxiety [64.4 (52, 0, 82.5), 75.3 (66.0, 89.5), 82.6 (78.5, 90.0), 83.6 (78.0, 91.0)] and concern about body image [76.8 (66.0, 92.0), 81.1 (76.5, 91.5), 85.5 (82.5, 94.0), 86.1 (82.0, 92.0)] were improved (all P<0.01); pelvic pain [5.4 (2.0, 8.0), 5, 0 (2.0, 7.8), 3.9 (1.0, 5.0), 3.0 (1.0, 5.0)], urinary incontinence [15.7 (7.0, 22.0), 11.1 (0, 17.5), 10.0 (0, 17.0), 9.9 (0, 16.0)], impotence [14.3 (4.2, 19.0), 12.2 (0, 16.8), 5.6 (0, 10.0), 5.2 (0.2, 8.0)], urinate [26.4 (13.0, 38.5), 13.9 (0, 20.0), 13.4 (2.5, 21.5), 13.2 (2.0, 20.0)] and mucous bloody stool [4.7 (3.0, 6.0), 2.6 (0, 5.0), 2.2 (0, 5.0), 1.9 (0, 4.0)] were improved as well (all P<0.01). The scores fluctuated in the improvement of male sexual function, abdominal pain, dry mouth, worry about body mass change, skin pain and dyspareunia, but the symptoms were significantly improved after ostomy reversal compared with before neoadjuvant therapy (all P<0.05). There were no significant changes in female sexual function, dysuria, dysgeusia and fecal incontinence after ostomy reversal compared with before neoadjuvant therapy (all P>0.05). (2) IIEF scale showed that all scores were similar before and after neoadjuvant therapy (all P>0.05). (3) Rectal and anal function scale revealed that before neoadjuvant therapy, before operation, 3 months and 12 months after stoma reversal, gas incontinence [3.1 (0, 4.0), 2.3 (0, 4.0), 1.8 (0, 4.0), 1.2 (0, 3.0)] and urgent defecation [7.2 (0, 11.0), 5.2 (0, 11.0), 2.9 (0, 9.0), 1.7 (0, 0)] were improved (all P<0.001). In terms of improving incomplete emptying sensation, the symptoms fluctuated, but the symptoms improved significantly after ostomy reversal compared with before neoadjuvant therapy (all P<0.05). While the symptoms of assistance with defecation [0 (0, 0), 0.7 (0, 1.0), 0.6 (0, 1.0), 0.7 (0, 1.0)] and defecation failure [0.2 (0, 0), 1.0 (0, 2.0), 0.8 (0, 1.5), 0.8 (0, 1.0)] showed a worsening trend (all P<0.001). Stratified analysis was performed on patients with different efficacy of neoadjuvant therapy to compare the changes in QoL before and after neoadjuvant therapy. Patients with less sensitive and more sensitive neoadjuvant therapy showed similar changes in function and symptoms. Patients with less sensitive therapy showed significant improvement in dysuria, urinary incontinence, skin pain and dyspareunia (all P<0.05), and the symptom of defecation frequency in more sensitive patients was significantly improved (P<0.05). Conclusions: For patients with LARC, neoadjuvant radiochemotherapy combined with radical LAR and protective stoma can improve QoL in many aspects. It is noted that patients show a worsening trend in the need for assistance with defecation and in defecation failure.

Progress on contact lens for extended ophthalmic drug delivery / 国际眼科杂志(Guoji Yanke Zazhi)

Conventional eye treatment formulation such as eye drops has shortcomings including low drug utilization and poor patient compliance. The contact lens(CL), well-known as visual correction lens, is considered to be a more promising ophthalmic drug delivery vehicle owing to its good biocompatibility, long-term wearing comfort, prolonged drug residence time and improved bioavailability. In order to improve the drug loading efficiency and prolong the release time, researchers have developed a variety of strategies to modify traditional CL, including the introduction of vitamin E molecular barrier, application of molecular imprinting technology of CL, increasing interactions between the drug and polymer matrix by introducing special genes, and incorporation of nanocarriers or drug-loaded polymer films. In this paper, the preparation methods and pros and cons of drug-loaded CL are reviewed. At last, the existing problems and future developments of CL as ophthalmic drug delivery carrier are briefly discussed.

Research progress of metabolic flux analysis technology in glucose metabolism pathway research / 药学学报

With the wide application of stable isotope tracer metabolomics technology, its comprehensive analysis and in-depth mining of data are particularly important, and metabolic flux analysis is one of the main technical means, especially in the study of glucose metabolism. Metabolic flux analysis technology combines isotope tracing with mathematical models to deduce and calculate the metabolic flux between metabolites. The metabolic flux provides more information for research and reflects a dynamic metabolic process more clearly and specifically. This paper reviews the basic process, precautions, and application examples of metabolic flux analysis in glucose metabolism research, and provides a reference for the application of metabolic flux analysis based on stable isotope tracer metabolomics in glucose metabolism research.

Effect of activation of Toll-like receptor signaling pathway of peripheral blood mononuclear cell in recombinant hepatitis B surface antigen immune response / 中华流行病学杂志

Objective: To explore the effect and mechanism of activation of peripheral blood mononuclear cell (PBMC) Toll-like receptor (TLR3) signaling pathway in recombinant HBsAg (rHBsAg) immune response. Methods: White blood cells were collected from peripheral blood of 13 healthy donors in the preparation of blood products. PBMC was isolated and treated with Poly I:C (Poly I:C group) and PBS (control group) respectively. 48 h later, some cells were collected and the expressions of TLR3 signaling pathway proteins were detected by flow cytometry. After activating (Poly I:C group)/inactivating (control group) TLR3 signaling pathway, rHBsAg was given to both groups for 72 h, and the proportions of DC, T, B cells and their subsets in PBMC were detected by flow cytometry. Paired t-test, paired samples wilcoxon signed-rank test and canonical correlation analyses were used for statistical analysis. Results: The percentage of TLR3 protein-positive cells (19.21%) and protein expression (8 983.95), NF-κB protein expression (26 193.13), the percentage of pNF-κB protein-positive cells (13.73%) and its proportion in NF-κB (16.03%), and the percentage of pIRF3 protein-positive cells (12.64%) and its proportion in IRF3 (21.80%) in Poly I:C group were higher than those in control group (11.54%, 8 086.00, 22 340.66, 8.72%, 9.71%, 9.57%, 19.12%) (P<0.05), and the percentage of TRIF protein-positive cells (89.75%) and protein expression (304 219.54) were higher in Poly I:C group than in the control group (89.64%, 288 149.72) (P>0.05). After PBMC stimulation by rHBsAg, the proportions of mDC (2.90%), pDC (1.80%), B cell (5.31%) and plasma cell (67.71%) in Poly I:C group were significantly higher than those in the control group (1.83%, 0.81%, 4.23%, 58.82%) (P<0.05). Results of canonical correlation analysis showed that the expression of TLR3 protein was positively correlated with the proportions of plasma cells, the expression of pIRF3 protein was positively correlated with the proportions of plasma cells and mDC, and the percentage of pNF-κB protein-positive cells and the percentage of pIRF3 protein-positive cells were positively correlated with the proportion of CD4+T cells. Conclusions: Poly I:C can activate TLR3/TRIF/NF-κB and TLR3/TRIF/IRF3 signaling pathway, promote the function of downstream signaling molecules, and then promote the maturation of DC, induce the immune responses of CD4+T cell, and promote the maturation and activation of B cells and the immune response of rHBsAg.

Cinnamaldehyde inhibits pancreatic cancer cell proliferation and sternness via modulation of CD44s/STAT3 signaling pathway / 中国药理学通报

Aim To explore the effects of cinnamaldehyde on the proliferation and stemness of pancreatic cancer PANC-1 cells, and its possible mechanism of action.Methods CCK8 assay was used to detect the effect of cinnamaldehyde treatment on cell viability at different concentrations(0, 5, 15, 20, 30, 50, 70, 100, 150 μmol·L-1)and different intervention time(24, 48, 72 h).CFSE proliferation assay was used to detect the inhibitory effects of cinnamaldehyde on PANC-1 cells.Colony formation assay was employed to determine the colony-forming ability of PANC-1 cells after cinnamaldehyde treatment.The sphere formation assay was employed to detect the effects of cinnamaldehyde on sphere-forming ability in PANC-1 cells.Western blot analysis and qRT-PCR analysis were applied to determine the expression levels of Nanog, Sox-2 and Oct-4.Flow cytometry was used to detect the percentage of CD44+CD24+ cells and ALDH+ cells in cinnamaldehyde treated and untreated PANC-1 cells.Western blot analysis was used to detect the effects of cinnamaldehyde on the expression of CD44s, p-STAT3 and STAT3 in PANC-1 cells.Results Cinnamaldehyde suppressed cell viability in a dose- and time-dependent manner, and inhibited tumor-cell proliferation and colony forming ability significantly in a dose-dependent manner in PANC-1 cells.Sphere-forming assay showed that cinnamaldehyde could significantly inhibit sphere-forming ability in suspension culture of PANC-1 cells.The mRNA and protein expression levels of three stemness-related genes were down-regulated after cinnamaldehyde treatment.In addition, cinnamaldehyde treatment significantly decreased the proportion of CD44+CD24+ cells and ALDH+ cells.Western blotting showed that cinnamaldehyde inhibited the expression of CD44s and p-STAT3, while it had no effect on the expression of STAT3.With the addition of STAT3 activator(Colivelin TFA), the inhibition of cinnamaldehyde on proliferation and tumor-cell stemness in PANC-1 cells was partially rescued.Conclusions Cinnamaldehyde significantly inhibits the proliferation and tumor-cell stemness of pancreatic cancer PANC-1 cells, and the mechanism could be related to the modulation of CD44s/STAT3 signaling pathway.

Application of electric tube stapler in laparoscopic colorectal tumor surgery / 中华胃肠外科杂志

Objective: To investigate the application of electric tube stapler in laparoscopic colorectal tumor surgery. Methods: A descriptive case series study was conducted. Clinical data of patients who underwent laparoscopic colorectal surgery in Peking Union Medical College Hospital in August 2021 using domestic electric tube stapler were collected to analyze the occurrence of postoperative anastomotic leakage, anastomotic bleeding and other complications as well as postoperative intestinal function recovery. Results: A total of 11 patients with colorectal tumor were enrolled in this study, including 8 males and 3 females. Eight patients underwent laparoscopic low anterior resection (1 patient underwent protective ileostomy), and three patients underwent laparoscopic sigmoid carcinoma radical resection. During operation, power system failure of stapler occurred in 1 patient, and the replacement manual device was used to complete the anastomosis. No anastomotic leakage or bleeding occurred in the cohort of patients. There was no conversion to laparotomy or conventional anastomosis. One patient developed acute myocardial infarction 2 days after surgery. The average time to the first flatus after surgery was (2.4±0.8) days and the average length of hospital stay was (10.0±6.1) days. Conclusions: The application of electric tube stapler in laparoscopic colorectal tumor surgery has many advantages, such as safe and effective anastomosis, low morbidity of postoperative complications, and rapid recovery of intestinal function. Domestic electric tube stapler can be applied in minimally invasive surgery for colorectal tumor.

Protective colostomy and protective ileostomy for the prevention of anastomotic leak in patients with rectal cancer after neoadjuvant chemoradiotherapy and radical surgery / 中华胃肠外科杂志

Objective: To investigate whether protective colostomy and protective ileostomy have different impact on anastomotic leak for rectal cancer patients after neoadjuvant chemoradiotherapy (nCRT) and radical surgery. Methods: A retrospectively cohort study was conducted. Inclusion criteria: (1) Standard neoadjuvant therapy before operation; (2) Laparoscopic rectal cancer radical resection was performed; (3) During the operation, the protective enterostomy was performed including transverse colostomy and ileostomy; (4) The patients were followed up regularly; (5) Clinical data was complete. Exclusion criteria: (1) Colostomy and radical resection of rectal cancer were not performed at the same time; (2) Intestinal anastomosis is not included in the operation, such as abdominoperineal resection; (3) Rectal cancer had distant metastasis or multiple primary colorectal cancer. Finally 208 patients were included in this study. They suffered from rectal cancer and underwent protective stoma in radical surgery after nCRT at our hospital from January 2014 to December 2018. There were 148 males and 60 females with age of (60.5±11.1) years. They were divided into protective transverse colostomy group (n=148) and protective ileostomy group (n=60). The main follow up information included whether the patient has anastomotic leak and the type of leak according to ISREC Grading standard. Besides, stoma opening time, stoma flow, postoperative hospital stay, stoma related complications and postoperative intestinal flora were also collected. Results: A total of 28 cases(13.5%) suffered from anastomotic leak and 26 (92.9%) of them happened in the early stage after surgery (less than 30 days) . As for these early-stage leak, ISREC Grade A happened in 11 cases(42.3%), grade B in 15 cases(57.7%) and no grade C occurred. There was no significant difference in the incidence [12.8% (19/148) vs. 15.0% (9/60) , χ(2)=0.171, P=0.679] or type [Grade A: 5.4%(8/147) vs. 5.1%(3/59); Grade B: 6.8%(10/147) vs. 8.5%(5/59), Z=0.019, P=1.000] of anastomotic leak between the transverse colostomy group and ileostomy group (P>0.05), as well as operation time, postoperative hospital stay, drainage tube removal time or stoma reduction time (P>0.05). There were 10 cases (6.8%) and 24 cases (40.0%) suffering from intestinal flora imbalance in protective transverse colostomy and protective ileostomy group, respectively (χ(2)=34.503, P<0.001). Five cases (8.3%) suffered from renal function injury in the protective ileostomy group, while protective colostomy had no such concern (P=0.002). The incidence of peristomal dermatitis in the protective colostomy group was significantly lower than that in the protective ileostomy group [12.8% (9/148) vs. 33.3%(20/60), χ(2)=11.722, P=0.001]. Conclusions: It is equally feasible and effective for rectal cancer patients after nCRT to carry out protective transverse colostomy or ileostomy in radical surgery. However, we should pay more attention to protective ileostomy patients, as they are at high risk of intestinal flora imbalance, renal function injury and peristomal dermatitis.

Prognosis and complications of local excision for rectal cancer after neoadjuvant chemoradiotherapy / 中华胃肠外科杂志

Objective: To investigate the prognosis and postoperative complications of local excision for rectal cancer after neoadjuvant chemoradiotherapy (nCRT). Methods: A descriptive case series study was carried out. Patient inclusion criteria: (1) patients who underwent local excision by transanal endoscopic microsurgery (TEM) after nCRT; (2) magnetic resonance evaluated tumor regression grade (mrTRG) as 1, 2 after nCRT;(3) American Society of Anesthesiologists class I to III. Patient exclusion criteria: (1) with multiple primary colorectal cancers; (2) with other malignant tumors within five years; (3) with emergency surgicery indications like digestive tract obstruction, perforation or bleeding. Clinicopathological and follow-up data of rectal cancer patients with obvious tumor regression after nCRT who underwent local excision in Peking Union Medical College Hospital from January 2010 to August 2019 were retrospectively collected. Outcome measures included disease-free survival (DFS), short-term postoperative complications, and at postoperative 1-year during follow up, gas continence, fecal continence, and quality of life (using the EORTC QLQ-CR29 scale, higher score indicated worse quality of life) at postoperative 1-year. Results: A total of 40 patients were included in this study. There were 27 males and 13 females with an average age of (66.7±12.3) years. Preoperative rectal ultrasound and other imaging examinations indicated that the tumor was located in the anterior wall in 16 cases, the lateral wall in 12 cases, and the posterior wall in 12 cases. The distance between the lower margin of the tumor and the anal verge was (4.3±1.2) cm before nCRT and (5.1±0.9) cm after nCRT. According to mrTRG, 31 cases were assessed as mrTRG 1 and 9 cases as mrTRG 2. All the patients received local extended excision of rectal cancer using TEM platform. A total of 19 cases(47.5%) suffered from complications within one month postoperatively. Clavien-Dindo grade I complications happened in 14 cases, grade II in 3 patients, and grade III in 2 cases, who all were healed by conservative treatment. Except that 2 patient presented severe low anterior resection syndrome (LARS) at 1 year postoperatively, no severe anal dysfunction was found in this cohort patients. EORTC QLQ CR29 scale results for quality of life showed that at 1 year after TEM excision, except taste (Z=-1.968, P=0.049), anxiety (Z=-3.624, P<0.001) and skin irritation (Z=-2.420, P=0.023) were worse than the situation before neoadjuvant therapy, there were no statistically significant differences in other assessment results between pre-operation and post-operation (all P>0.05). Postoperative pathological results indicated complete tumor regression (pTRG0) in 17 cases, moderate remission (pTRG1) in 13, and mild remission (pTRG2) in 10. During the follow-up of (49.1±29.6) months, 3 patients had local recurrence and 4 had distant metastasis (3 patients with liver metastasis and 1 patient with lung metastasis followed by liver metastasis). No death was found and the 5-year disease-free survival (DFS) was 84.3%. Conclusions: Local excision through TEM following nCRT not only can be adopted as an important means to accurately determine complete clinical remission (cCR), but also has high therapeutic value for rectal cancer patients presenting cCR or near cCR, with little impact on defecatory function and quality of life. However, the morbidity of complication of TEM excision after nCRT is relatively high and there is a risk of recurrence and metastasis. Therefore, it is still necessary to strictly select the indications of local excision.

Projects status analysis of occupational respiratory diseases funded by the National Natural Science Foundation of China from 1987 to 2018 / 中国职业医学

OBJECTIVE: To analyze the funding status of the National Natural Science Fund(NNSF) in the field of occupational respiratory disease(ORD) research in China. METHODS: Through the NNSF Committee Science Foundation sharing service network database, we collected the information of funded projects in the field of ORD research in China from 1987 to 2018, and analyzed the funding expenditure, funding categories, supporting units and research contents. RESULTS: A total of 106 NNSF funded projects were obtained in the research field of ORD in China in the period 1987-2018, and the total amount of funding was 37.945 million yuan. The number of funded projects, the average and the total amounts of fundings showed an increasing trend year by year(all P<0.05). The main types of funded projects were general projects and Youth Science Foundation projects(97.2%). The funded projects and funds were mainly concentrated in colleges and universities, accounting for 79.2% and 83.4% respectively. Beijing(29 items, 27.4%), Hebei(13 items, 12.3%) and Jiangsu(11 items, 10.4%) were the top three provinces and municipalities in the number of funded projects. Silicosis, pulmonary fibrosis, quartz, alveolar macrophages and acute lung injury were the top five keywords of funded project items, and the research types mainly focused on the mechanism of diseases. CONCLUSION: The NNSF funding is imbalanced in the types of funding, supporting units, and regional distribution on ORD research field in China. It is suggested that the funding structure of NNSF should be optimized, interdisciplinary research should be encouraged and expanded, and cooperation among different institutions and regions should be promoted.

Factors influencing protective behaviours during haze episodes in Singapore: A population-based study

INTRODUCTION@#Haze is a recurrent problem in Southeast Asia. Exposure to haze is linked to ophthalmic, respiratory and cardiovascular diseases, and mortality. In this study, we investigated the role of demographic factors, knowledge and perceived risk in influencing protective behaviours during the 2013 haze in Singapore.@*METHODS@#We evaluated 696 adults in a cross-sectional study. Participants were sampled via a 2-stage simple random sampling without replacement from a large residential district in Singapore in 2015. The questionnaire measured the participant's knowledge, perceived risk and behaviours during the Southeast Asian haze crisis in 2013. Reliability and validity of the questionnaire were assessed using comparative fit index (≥0.96) and root mean square error of approximation (≤0.05). We performed structural equation modelling to examine the relationship between the hypothesised factors and protective behaviours.@*RESULTS@#More than 95% of the individuals engaged in at least 1 form of protective behaviour. Knowledge was strongly associated with protective behaviours via direct effect (β=0.45, 95% CI 0.19-0.69, @*CONCLUSION@#Knowledge was associated with protective behaviours, suggesting the importance of public education. Efforts should target those of lower education level and smokers. The wearing of N95 masks correlates with uptake of other protective behaviours.

Application of stable isotope-resolved metabolomics in glucose catabolism / 药学学报

With the rapid development of high sensitivity detection techniques such as nuclear magnetic resonance and mass spectrometry, stable isotope-resolved metabolomics has been widely used in elucidating the regulatory mechanism of metabolic pathways and metabolic flow analysis, and some breakthroughs have been made. In this paper the application of stable isotope-resolved metabolomics in glucose catabolic regulation, metabolic flow analysis and functional interpretation of key metabolic pathways is reviewed, providing references for the wider use and application of this technology.

Trends in the biological functions and medical applications of extracellular vesicles and analogues

Natural extracellular vesicles (EVs) play important roles in many life processes such as in the intermolecular transfer of substances and genetic information exchanges. Investigating the origins and working mechanisms of natural EVs may provide an understanding of life activities, especially regarding the occurrence and development of diseases. Additionally, due to their vesicular structure, EVs (in small molecules, nucleic acids, proteins, etc.) could act as efficient drug-delivery carriers. Herein, we describe the sources and biological functions of various EVs, summarize the roles of EVs in disease diagnosis and treatment, and review the application of EVs as drug-delivery carriers. We also assess the challenges and perspectives of EVs in biomedical applications.

Transcriptome-wide Identification and Expression Profiles of WRKY Transcription Factor in Prunella vulgaris / 中国实验方剂学杂志

Objective:To identify WRKY genes from the transcriptome dataset of Prunella vulgaris by bioinformatics method, and analyze the protein characteristics and expression level of these genes. Method:WRKY transcription factor were identified from the P. vulgaris transcriptome database，their motif，physical and chemical properties，functional annotations，family evolution and expression patterns were analyzed, and their functions were predicted. Result:A total of 23 WRKY transcription factors were identified from P. vulgaris in this study by computational prediction method.Structural analysis found that WRKY proteins contained a highly conserved motif WRKYGQK. Phylogenetic analysis of WRKYs together with the homologous genes from Arabidopsis thaliana could be divided into two groups（group Ⅰ-Ⅱ）. There were 7 members in group Ⅰ，and 16 members in group Ⅱ, group Ⅱ was subdivided into five subgroups，namely group Ⅱb （3 members），Ⅱc（5 members），Ⅱd（3 members），Ⅱe（5 members）. The physical and chemical properties of WRKY protein showed that the amino acid number was between 85 and 599，the molecular weight was between 9 527.5-66 438.45 Da，the theoretical isoelectric point was between 5.01-9.83.Among them, c13719.graph_c0，c32199.graph_c0，c24547.graph_c0，c37881.graph_c0 may play a role in the regulation of secondary metabolitessynthesis of P. vulgaris.And c32199.graph_c0，c26537.graph_c0，c23728.graph_c0 may has an effect in identifying and defensing pathogens in P. vulgaris.The transcriptional profiles of these 23 WRKY genes in various tissues were investigated using transcriptome dataset.The results showed that the expression level of WRKY genes varied significantly in different tissues. Conclusion:This study identifies the organization and transcriptional profiles of PmWRKY genes for the first time, so as to provide the helpful information for further studies of functions of WRKYs.

Comparative transcriptome analysis of differential expression in different tissues of Prunella vulgaris / 中草药

Objective: To compare and analyze the transcriptome of ears, leaves and stems of Prunella vulgaris, and excavate the key enzyme genes related to the secondary metabolism biosynthesis of P. vulgaris. Methods: The transcriptome of ears, leaves and stems of P. vulgaris were sequenced by Illumina high-throughput sequencing technology. Additionally biosynthesis related enzyme gene of secondary metabolism were identified from differentially expressed genes. Results: In the transcripts of three different tissues of P. vulgaris, a total of 8 270 Unigenes differed significantly between at least two tissues. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis of genes differentially expressed in different tissues showed that the expression of phenylpropanoid biosynthesis genes varied greatly. A total of 31 triterpenoid biosynthesis-related Unigenes, 16 phenolic acid biosynthesis-related Unigenes, and 113 P450s-related Unigenes were identified in the differentially expressed genes. Conclusion: This study provides a basis for the subsequent discovery of functional genes related to the secondary metabolism synthesis pathway of P. vulgaris, and plays a foundation for the regulation of secondary metabolism biosynthesis of P. vulgaris.