Role of lipopolysaccharide in the development and progression of liver cancer / 临床肝胆病杂志

Liver cancer is an important public health issue worldwide. With the improvements in high-throughput sequencing and gene editing techniques in recent years, studies have further revealed the biological mechanism of intestinal microflora in the development, progression, and metastasis of liver cancer via the gut-liver axis, and in particular, it has been found that lipopolysaccharide, a component of the outer membrane of gram-negative bacteria, can cause downstream immune cascade reactions. This article reviews the possible mechanism of action of intestinal microflora lipopolysaccharide in the development and progression of liver cancer from the aspects of the association between intestinal environmental changes and liver cancer, immunoregulation by lipopolysaccharide, and preclinical treatment.

Discovery of novel phosphodiesterase-1 inhibitors for curing vascular dementia: Suppression of neuroinflammation by blocking NF-κB transcription regulation and activating cAMP/CREB axis

Vascular dementia (VaD) is the second commonest type of dementia which lacks of efficient treatments currently. Neuroinflammation as a prominent pathological feature of VaD, is highly involved in the development of VaD. In order to verify the therapeutic potential of PDE1 inhibitors against VaD, the anti-neuroinflammation, memory and cognitive improvement were evaluated in vitro and in vivo by a potent and selective PDE1 inhibitor 4a. Also, the mechanism of 4a in ameliorating neuroinflammation and VaD was systematically explored. Furthermore, to optimize the drug-like properties of 4a, especially for metabolic stability, 15 derivatives were designed and synthesized. As a result, candidate 5f, with a potent IC50 value of 4.5 nmol/L against PDE1C, high selectivity over PDEs, and remarkable metabolic stability, efficiently ameliorated neuron degeneration, cognition and memory impairment in VaD mice model by suppressing NF-κB transcription regulation and activating cAMP/CREB axis. These results further identified PDE1 inhibition could serve as a new therapeutic strategy for treatment of VaD.

Quality analysis of surgical specimens of rectal cancer in the Chinese taTME registry coll-aborative database: a nationwide registered study / 中华消化外科杂志

Objective:To analyze the quality of surgical specimens of rectal cancer in the Chinese transanal total mesorectal excision (taTME) registry collaborative (CTRC) database.Methods:The retrospective and descriptive study was conducted. Based on the concept of real-world research, the clinicopathological data of 1 761 patients with rectal cancer in the CTRC database who underwent taTME in 40 medical centers, including the Beijing Friendship Hospital of Capital Medical University et al, from November 15, 2017 to December 31, 2022 were collected. There were 1 212 males and 549 females, aged 62(range, 53-68)years. Observation indicators: (1) preoperative examinations; (2) neoadjuvant therapy; (3) postoperative examinations. Measurement data with skewed distri-bution were represented as M(range). Count data were described as absolute numbers. Results:(1) Preoperative examinations. Of the 1 761 patients, 1 324 patients underwent preoperative pelvic magnetic resonance imaging examination, and the results showed that 4 cases as clinical T0 stage, 30 cases as clinical T1 stage, 250 cases as clinical T2 stage, 828 cases as clinical T3 stage, 141 cases as clinical T4 stage, 11 cases as clinical Tx stage, 60 cases missing clinical T staging data, 490 cases as clinical N0 stage, 373 cases as clinical N1 stage, 311 cases as clinical N2 stage, 86 cases as clinical Nx stage, 64 cases missing clinical N staging data, 156 cases with mesorectal fascia invasion, 223 cases with extraintestinal blood vessels invasion. The distance from lower margin of tumor to anal margin of 1 324 patients was 50(range, 40-60)mm. (2) Neoadjuvant therapy. Of the 1 761 patients, 873 patients underwent neoadjuvant therapy, including 17 cases receiving radiotherapy alone, 155 cases receiving chemotherapy alone, 43 cases receiving short-course simultaneous chemoradiotherapy, 26 cases receiving short-course simultaneous chemoradiotherapy and delayed surgery, 1 case receiving contact radiotherapy, 277 cases receiving long-course simultaneous chemoradiotherapy, 9 cases receiving other treatments, and 345 cases missing neoadjuvant therapy data. (3) Postoperative examinations. Of the 1 761 patients, 1 584 cases achieved R 0 resection, 23 cases achieved R 1 resection, 1 case achieved R 2 resection, and there were 153 cases missing surgical margin data. The tumor diameter, number of lymph nodes harvest and positive rate of intravascular tumor thrombus were 30(range, 20-45)cm, 13(range, 10-17) and 20.794%(330/1 587) in 1 761 patients. There were 1 647 patients with circumferential margin records, which showed positive in 51 cases, and the minimum distance from deep part of tumor to circumferential margin was 5(rang, 3-13)mm in 1 647 patients. There were 547 cases with distal margin records, which showed positive in 4 cases, and the distance from lower margin of tumor to distal margin was 20(10-25)mm in 547 cases. There were 1 698 patients with specimen integrity records, which showed intact specimen in 1 436 cases, fair specimen in 233 cases, poor specimen in 8 cases, unevaluated specimen in 21 cases, and there were 20 cases with rectal tube perforation. Of the 1 761 patients, cases as pathological T0 stage, Tis stage, T1 stage, T2 stage, T3 stage, T4 stage was 103, 23, 145, 515, 712, 179, respectively, and there were 4 cases of pathology that could not be evaluated and 80 cases missing pathological T staging data. Of the 1 761 patients, cases as pathological N0 stage, N1a stage, N1b stage, N1c stage, N2a stage, N2b stage was 1 117, 189, 133, 66, 109, 68, respectively, and there were 79 cases missing pathological N staging data. Of the 1 761 patients, there were 79 cases with distant metastasis, 1 591 cases without distant metastasis, and 91 cases without data of tumor metastasis. Of the 873 patients undergoing neoadjuvant therapy, there were 405 patients with tumor regression grade records including 105 cases as grade 1, 142 cases as grade 2, 91 cases as grade 3, 43 cases as grade 4, 24 cases as grade 5. Conclusions:In China, the quality of surgical specimens of taTME for rectal cancer is good with low positive rate of resection margin. It is recommended that using a formatted postoperative pathological report for good quality control of pathological report of surgical specimen.

Clinical value of esophageal-jejunal Orvil TM anastomosis and Overlap anastomosis in laparos-copic radical total gastrectomy of adenocarcinoma of esophagogastric junction / 中华消化外科杂志

Objective:To investigate the clinical value of esophageal-jejunal OrVil TM anas-tomosis and Overlap anastomosis in laparoscopic radical total gastrectomy of adenocarcinoma of esophagogastric junction (AEG). Methods:The retrospective cohort study was conducted. The clinicopathological data of 112 patients with AEG who were admitted to the First Hospital of Jilin University from July 2017 to August 2022 were collected. There were 87 males and 25 females, aged (64±8)years. All 112 patients underwent laparoscopic total gastrectomy and D 2 lymphadenectomy, in which 61 cases with esophageal-jejunal OrVil TM anastomosis were divided into the OrVil TM group, 51 cases with esophageal-jejunal Overlap anastomosis were divided into the Overlap group. Observa-tion indicators: (1) surgical situations; (2) postoperative complications; (3) influencing factors for patients undergoing esophageal-jejunal OrVil TM anastomosis. Measurement data with normal distri-bution were represented as Mean± SD, and comparison between groups was conducted using the independent sample t test. Measurement data with skewed distribution were represented as M( Q1, Q3), and comparison between groups was conducted using the non-parameter test. Count data were described as absolute numbers, and comparison between groups was conducted using the chi-square test or Fisher exact probability. Logistic regression model was used for multivariate analysis. Results:(1) Surgical situations. The esophageal invasion length and tumor diameter was 1.0(0.7,2.0)cm and (6.3±2.7)cm in patients of the OrVil TM group, versus 0.2(0.1,0.5)cm and (4.7±2.2)cm, respectively, in patients of the Overlap group, showing significant differences in the above indicators between the two groups ( Z=?6.14, t=3.26, P<0.05). (2) Postoperative complications. Cases with complications ≥Ⅲa grade of Clavien-Dindo classification, cases with respiratory system complications, cases with hydrothorax were 13, 17, 13 in the OrVil TM group, versus 4, 5, 4 in the Overlap group, showing significant differences in the above indicators between the two groups ( χ2=3.91, 5.74, 3.91, P<0.05). Cases underwent readmission within postoperative 30 days were 3 and 1 in the OrVil TM group and the Overlap group, respectively, and all patients recovered after symptomatic treatment. There were 2 cases died after operation in the OrVil TM group and none of patients died after operation in the Overlap group. (3) Influencing factors for patients undergoing esophageal-jejunal OrVil TM anastomosis. Results of multivariate analysis showed that esophageal invasion length was an independent factor influencing for patients undergoing esophageal-jejunal OrVil TM anastomosis ( odds ratio=8.25, 95% confidence interval as 3.41?19.96, P<0.05). Conclusions:Compared with esophageal-jejunal Overlap anastomosis, choosing the esophageal-jejunal Orvil TM anastomosis during laparoscopic radical total gastrectomy can take benefit to the proximal margin of patients with AEG. However, the ratios of complications ≥ Ⅲa grade of Clavien-Dindo classification, respiratory system complications and hydrothorax associated to OrVil TM anastomosis are relatively increased. Esophageal invasion length is an independent influencing factor for patients undergoing esophageal-jejunal OrVil TM anastomosis.

The safety and short-term efficacy of laparoscopic proximal gastrectomy for proximal gastric cancer and adenocarcinoma of esophagogastric junction: a multicenter study / 中华消化外科杂志

Objective:To investigate the safety and short-term efficacy of laparoscopic pro-ximal gastrectomy (LPG) for proximal gastric cancer and adenocarcinoma of esophagogastric junction.Methods:The retrospective cohort study was conducted. The clinicopathological data of 385 patients with proximal gastric cancer and adenocarcinoma of esophagogastric junction who underwent LPG in the 15 medical centers, including the First Affiliated Hospital of Xiamen University et al, from January 2014 to March 2022 were collected. There were 304 males and 81 females, aged (63±9)years. Of the 385 patients, 335 cases undergoing LPG were divided into the laparoscopic group and 50 cases undergoing open proximal gastrectomy were divided into the open group. Observation indicators: (1) intraoperative and postoperative situations; (2) follow-up; (3) stratified analysis. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was conducted using the t test. Measurement data with skewed distribution were represented as M(range), and comparison between groups was conducted using the Wilcoxon rank sum test. Count data were described as absolute numbers, and comparison between groups was conducted using the chi-square test or Fisher exact probability. Repeated measurement data were analyzed using the repeated ANOVA. Results:(1) Intraoperative and postoperative situations. The operation time, cases with reconstruction of digestive tract as esophagogastric anastomosis and esophageal-jejunal anastomosis, cases with postoperative pathological staging as stage 0?Ⅰ and stage Ⅱ?Ⅲ, duration of postoperative hospital stay, cases with postoperative early complications were (212±96)minutes, 270, 65, 177, 107, 10(range, 8?14)days, 40 in patients of the laparoscopic group, with 51 cases missing the data of postoperative pathological staging. The above indicators were (174±90)minutes, 39, 11, 22, 28, 10(range, 8?18)days, 10 in patients of the open group. There were significant differences in the opera-tion time and postoperative pathological staging between the two groups ( t=2.62, χ2=5.93, P<0.05), and there was no significant difference in the reconstruction of digestive tract, duration of post-operative hospital stay, postoperative early complications between the two groups ( χ2=0.19, Z=0.40, χ2=2.50, P>0.05). (2) Follow-up. Of the 385 patients,202 cases were followed up during the post-operative 12 months, including 187 cases in the laparoscopic group and 15 cases in the open group. Cases with reflux esophagitis, cases with esophageal anastomotic stenosis were 48, 11 in patients of the laparoscopic group, versus 5, 2 in patients of the open group, showing no significant difference in the above indicators between the two groups ( P>0.05). The body mass index (BMI), hemoglobin (Hb), albumin (Alb) at postoperative 6 months and 12 months were (21±3)kg/m 2, (130±15)g/L, (40±4)g/L and (21±3)kg/m 2, (132±14)g/L, (41±4)g/L in patients of the laparoscopic group, versus (21±3)kg/m 2, (121±19)g/L, (37±5)g/L and (21±3)kg/m 2, (125±21)g/L, (43±6)g/L in patients of the open group. There were significant differences in postoperative Hb between the two groups ( Fgroup=5.88, Ftime=5.49, Finteraction=19.95, P<0.05) and there were significant differences in time effect of postopera-tive BMI and Alb between the two groups ( Ftime=9.53, 49.88, P<0.05). (3) Stratified analysis. ① Incidence of postoperative of reflux esophagitis and esophageal anastomotic stenosis in patients with different reconstruction of digestive tract. Of the 202 patients, cases with reconstruction of digestive tract as esophagogastric anastomosis and esophageal-jejunal anastomosis were 168 and 34, respectively. The incidence rates of postoperative of reflux esophagitis were 26.79%(45/168)and 23.53%(8/34)in cases with reconstruction of digestive tract as esophagogastric anastomosis and esophageal-jejunal anastomosis, showing no significant difference between them ( χ2=0.16, P>0.05). Cases undergoing esophageal anastomotic stenosis were 13 in patients with reconstruction of diges-tive tract as esophagogastric anastomosis. ② The BMI, Hb, Alb in patients with different reconstruc-tion of digestive tract. The BMI, Hb, Alb were (24±3)kg/m 2, (135±20)g/L, (41±5)g/L in the 168 patients with reconstruction of digestive tract as esophagogastric anastomosis before the operation, versus (23±3)kg/m 2, (130±19)g/L, (40±4)g/L in the 34 patients with reconstruction of digestive tract as esophageal-jejunal anastomosis before the operation, showing no significant difference between them ( t=1.44, 1.77, 1.33, P>0.05). The BMI, Hb, Alb at postoperative 6 months and 12 months were (21±3)kg/m 2, (128±16)g/L, (39±4)g/L and (21±3)kg/m 2, (131±16)g/L, (41±4)g/L in the 168 patients with reconstruction of digestive tract as esophagogastric anastomosis, versus (20±4)kg/m 2, (133±13)g/L, (43±3)g/L and (21±3)kg/m 2, (135±12)g/L, (44±3)g/L in the 34 patients with reconstruction of digestive tract as esophageal-jejunal anastomosis. There were significant differences in the group effect and time effect of postoperative Alb between patients with different reconstruction of diges-tive tract ( Fgroup=15.82, Ftime=5.43, P<0.05), and there was also a significant difference in the time effect of postoperative BMI between them ( Ftime=4.22 , P<0.05). Conclusion:LPG can be used to the treatment of proximal gastric cancer and adenocarcinoma of esophagogastric junction, with a good safety and short-term efficacy.

Neurologic involvement in children with coronavirus disease 2019 / 中国小儿急救医学

The clinical manifestations of neuropathies associated with novel coronavirus infection are diverse, including headache, mental disorders, acute encephalitis(meningitis), acute disseminated cerebrospinal meningitis, Guillain-Barre syndrome, acute encephalopathy and even acute (hemorrhagic) necrotic encephalopathy, which can be attributed to a variety of potential pathophysiological mechanisms.The severity of cytokine storm, vascular endothelial cell injury (including blood-brain barrier) and hypoxic ischemic injury determines the prognosis of infected patients.The treatment mainly includes general supportive therapy and immune regulation.Clinicians need to monitor and evaluate the degree of brain dysfunction and prognosis, and ensure timely treatment.

Research progress of circadian rhythm and circadian clock gene regulation in the development of myopia / 国际眼科杂志(Guoji Yanke Zazhi)

With the development of society, the incidence of myopia and the population of myopia has increased year by year, which has become a major public health problem. Therefore, the research on the pathogenesis and prevention and control measures of myopia is imminent. In recent years, the role of the biological clock in the development of myopia has gradually attracted scholars interest. Now the author starts from the impact of the biological clock on the axial length, retina and choroid in the development of myopia. In order to provide new ideas for the study of prevention and control measures and the pathogenesis of myopia, a brief review is made from the perspective of contemporary society and disrupted body clock.

Clinical management and prognosis for descending necrotizing mediastinitis / 中华耳鼻咽喉头颈外科杂志

Objective: To investigate the clinical characteristics, treatment experiences and prognostic factors for descending necrotizing mediastinitis (DNM). Methods: A retrospective analysis was performed on the data of 22 patients with DNM diagnosed and treated in Henan Provincial People's Hospital from January 2016 to August 2022, including 16 males and 6 females, aged 29-79 years. After admission, all patients underwent CT scanning of the maxillofacial, cervical, and thoracic regions to confirm their diagnoses. Emergency incision and drainage were performed. The neck incision was treated with continuous vacuum sealing drainage. According to the prognoses, the patients were divided into cure group and death group, and the prognostic factors were analyzed. SPSS 25.0 software was used to analyze the clinical data. Rusults: The main complaints were dysphagia (45.5%, 10/22) and dyspnea (50.0%, 11/22). Odontogenic infection accounted for 45.5% (10/22) and oropharyngeal infection accounted for 54.5% (12/22). There were 16 cases in the cured group and 6 cases in the death group, with a total mortality rate of 27.3%. The mortality rates of DNM typeⅠand typeⅡwere respectively 16.7% and 40%. Compared with the cured group, the death group had higher incidences for diabetes, coronary heart disease and septic shock (all P<0.05). There were statistically significant differences between the cure group and the death group in procalcitonin level (50.43 (137.64) ng/ml vs 2.92 (6.33) ng/ml, M(IQR), Z=3.023, P<0.05) and acute physiology and chronic health evaluation Ⅱ(APACHEⅡ) score (16.10±2.40 vs 6.75±3.19, t=6.524, P<0.05). Conclution: DNM is rare, with high mortality, high incidence of septic shock, and the increased procalcitonin level and APACHE Ⅱ score combined diabetes and coronary heart disease are the poor prognostic factors for DNM. Early incision and drainage combined with continuous vacuum sealing drainage technique is a better way to treat DNM.

Phenotype-genotype analysis of the autosomal recessive hereditary hearing loss caused by OTOA variations / 中华耳鼻咽喉头颈外科杂志

Objective: To analyze the phenotypic-genotypic characteristics of hereditary deafness caused by OTOA gene variations. Methods: Family histories, clinical phenotypes and gene variations of six pedigrees were analyzed, which were diagnosed with hearing loss caused by OTOA gene variations at the PLA General Hospital from September 2015 to January 2022. The sequence variations were verified by Sanger sequencing and the copy number variations were validated by multiplex ligation-dependent probe amplification (MLPA) in the family members. Results: The hearing loss phenotype caused by OTOA variations ranged from mild to moderate in the low frequencies, and from moderate to severe in the high frequencies in the probands, which came from six sporadic pedigrees, among which a proband was diagnosed as congenital deafness and five were diagnosed as postlingual deafness. One proband carried homozygous variations and five probands carried compound heterozygous variations in OTOA gene. Nine pathogenic variations (six copy number variations, two deletion variations and one missense variation) and two variations with uncertain significance in OTOA were identified in total, including six copy number variations and five single nucleotide variants, and three of the five single nucleotide variants were firstly reported [c.1265G>T(p.Gly422Val),c.1534delG(p.Ala513Leufs*11) and c.3292C>T(p.Gln1098fs*)]. Conclusions: OTOA gene variations can lead to autosomal recessive nonsyndromic hearing loss. In this study, the hearing loss caused by OTOA defects mostly presents as bilateral, symmetrical, and postlingual, and that of a few presents as congenital. The pathogenic variations of OTOA gene are mainly copy number variations followed by deletion variations and missense variations.

Whole-course management strategies for gastroesophageal reflux disease: an evidence mapping study based on clinical practice guidelines / 中华胃肠外科杂志

Gastroesophageal reflux disease (GERD) is one of the most common digestive diseases with high incidence, complicated clinical symptoms, difficulties in standard treatment, and heavy medical burden. At present, some GERD-relevant clinical practice guidelines (CPGs) have been issued by different countries and academic organizations, but some recommendations were inconsistent, which has caused some problems for the current clinical whole-course management of GERD. To summarize the relevant evidence among the CPGs on GERD and formulate the whole- course management strategies, we included GERD-relevant CPGs published or updated after 2010 by searching websites of guidelines, relevant professional societies, and electronic databases. We extracted the recommendations and summarized the evidence from the aspects of symptoms, epidemiology, diagnosis and treatment, which was presented in the form of evidence mapping. We included 24 CPGs, including three in Chinese and 21 in English. The clinical practice management strategies of GERD were formulated based on the evidence from the aspects of clinical symptoms, diagnostic methods, medical treatment, anti-reflux surgery and endoscopic treatment, psychological treatment, and traditional Chinese medicine treatment.

Therapeutic potential of targeting SIRT1 for the treatment of Alzheimer's disease / 生理学报

Silent information regulator 1 (SIRT1) is one of the seven mammalian proteins of the sirtuin family of NAD+-dependent deacetylases. SIRT1 plays a pivotal role in neuroprotection and ongoing research has uncovered a mechanism by which SIRT1 may exert a neuroprotective effect on Alzheimer's disease (AD). Growing evidence demonstrates that SIRT1 regulates many pathological processes including amyloid-β precursor protein (APP) processing, neuroinflammation, neurodegeneration, and mitochondrial dysfunction. SIRT1 has recently received enormous attention, and pharmacological or transgenic approaches to activate the sirtuin pathway have shown promising results in the experimental models of AD. In the present review, we delineate the role of SIRT1 in AD from a disease-centered perspective and provides an up-to-date overview of the SIRT1 modulators and their potential as effective therapeutics in AD.

Empirical analysis on lumbar disc herniation treated with "sinew-bone three needling technique" of Chinese medicine / 中国针灸

The paper presents professor WU Han-qing's experience in treatment of lumbar disc herniation (LDH) with "sinew-bone three needling technique" of Chinese medicine. Based on the theory of meridian sinew, the points are located by "three-pass method" in terms of the distribution of meridian sinew and syndrome/pattern differentiation. The cord-like muscles and adhesion are relieved by relaxing technique to work directly on the affected sites and alleviate the local compression to the nerve root. The needle technique is operated flexibly according to the affected regions involved, due to which, the needling sensation is increased while the safety ensured. As a result, the meridian qi is enhanced, the mind and qi circulation is regulated; and the clinical effect is improved.

Advance on small molecule self-assembled nano-drug delivery system / 药学学报

Since the application of biomedical nanotechnology in the field of drug delivery breathes new life into the research and development of high-end innovative agents, a substantial number of novel nano-drug delivery systems (nano-DDSs) have been successively developed and applied in the clinical practice. Among them, small molecule pure drug and prodrug-based nanoassemblies have grasped great attention, owing to the facile fabrication, ultrahigh drug loading and feasible industrial production. Herein, we provide an overview on the latest updates of small-molecule nanoassemblies. Firstly, the self-assembled prodrug-based nano-DDSs are introduced, including nanoassemblies formed by amphiphilic monomeric prodrugs, hydrophobic monomeric prodrugs and dimer monomeric prodrugs. Then, the recent advances on nanoassemblies of small molecule pure chemical drugs and biological drugs are presented. Furthermore, carrier-free small-molecule hybrid nanoassemblies of pure drugs and/or prodrugs are summarized and analyzed. Finally, the rational design, application prospects and clinical challenges of small-molecule self-assembled nano-DDSs are discussed and highlighted. This review aims to provide scientific reference for constructing the next generation of nanomedicines.

Recommendations on off-label antibiotics use in PICU / 中国小儿急救医学

Off-label antibiotics use in pediatric intensive care unit is not rare.Off-label antibiotics use is due to indication, age, dosage, frequency, route and method of administration, course of treatment, etc.It is necessary and reasonable for off-label antibiotics use in clinical practice, but there are also some risks.Off-label antibiotics use in clinical practice should follow the corresponding principles and standardized management.Drug treatment decisions should always be made on the basis that the individual child would be ultimately benefit.

MET inhibitor tepotinib antagonizes multidrug resistance mediated by ABCG2 transporter: In vitro and in vivo study

Overexpression of ABCG2 transporter in cancer cells has been linked to the development of multidrug resistance (MDR), an obstacle to cancer therapy. Our recent study uncovered that the MET inhibitor, tepotinib, is a potent reversal agent for ABCB1-mediated MDR. In the present study, we reported for the first time that the MET inhibitor tepotinib can also reverse ABCG2-mediated MDR in vitro and in vivo by directly binding to the drug-binding site of ABCG2 and reversibly inhibiting ABCG2 drug efflux activity, therefore enhancing the cytotoxicity of substrate drugs in drug-resistant cancer cells. Furthermore, the ABCB1/ABCG2 double-transfected cell model and ABCG2 gene knockout cell model demonstrated that tepotinib specifically inhibits the two MDR transporters. In mice bearing drug-resistant tumors, tepotinib increased the intratumoral accumulation of ABCG2 substrate drug topotecan and enhanced its antitumor effect. Therefore, our study provides a new potential of repositioning tepotinib as an ABCG2 inhibitor and combining tepotinib with substrate drugs to antagonize ABCG2-mediated MDR.

Survey on occupational hazards of enterprises in Pingshan district of Shenzhen City / 中国职业医学

@#Abstract: Objective To analyze the occupational hazards of enterprises in Pingshan district of Shenzhen in 2017. Methods Occupational hazards were analyzed in 200 enterprises in Pingshan district of Shenzhen City selected using stratified Results random sampling method. A total of 24 industries were involved in the 200 enterprises. The declaration rate of ， occupational hazards was 91.5% and the exposure rate of occupational hazards among workers was 49.2%. The regular monitoring rate of occupational hazard factors in workplaces of the enterprises was 79.5%. There were 129 kinds of occupational ， ， hazard factors of which 19 factors exceeded the national occupational exposure limit accounting for 14.7%. The over standard ， ， ， ， ， ， ， ， rates of noise silica dust cotton dust methanol toluene and other dust were 28.7% 13.6% 11.8% 5.86% 0.5% and ， ， 0.4% respectively. There were 13 kinds of occupational hazard factors in the workplace of metal products industry all of which （ ） exceeded the occupational exposure limit. The exposure rate 56.7% of occupational hazard factors in workers was the highest. Conclusion ， ， The main occupational hazard factors were noise dust and chemical factor and the major occupational hazard industry was metal manufacturing in Pingshan district of Shenzhen City.

Ten directions for improving clinical therapeutic effect of pancreatic cancer in the future / 中华外科杂志

Pancreatic cancer is one of the most malignant digestive system tumors. In the recent decade, the effect of diagnosis and treatment of pancreatic cancer has improved due to the renewal of treatment concept and the popularization of effective treatment. However, the overall efficacy of pancreatic cancer is still dismal and the 5-year survival rate is only about 10%. Further improving the diagnosis and treatment of pancreatic cancer is the top priority of oncology research and clinical practice. Based on past clinical and scientific research experience, the authors have proposed ten hot spots and future directions for a reference, which focusing on early prevention, early diagnosis, and early treatment of pancreatic cancer, molecular typing and precise treatment, new drug development and regimen combination, surgical technology and strategy change, model establishment and database development, as well as innovation of traditional Chinese medicine and breakthrough of treatment concept. A breakthrough in the diagnosis and treatment of pancreatic cancer in the next ten years is raising hope, when doctors can truly prevent and control pancreatic cancer.

Application of two RT-PCR methods for detection of norovirus in market-sold oysters and norovirus genetic characteristic analysis, a survey conducted in Beijing / 中华流行病学杂志

Objective: To evaluate the application of real-time RT-PCR and semi-nested RT-PCR in the detection of norovirus in oysters and analyzing the genetic characteristics of the isolates. Methods: Real-time fluorescent RT-PCR and semi-nested RT-PCR were used to detect norovirus GⅠ/GⅡ in fresh oysters collected from the markets in Beijing from November 2014 to October 2015. The detection rate of the parallel test was also analyzed. In addition, the reliability of semi-nested RT-PCR was evaluated by agreement rate and consistency test (Kappa value). The positive products of norovirus GⅠ/GⅡ capsid protein region gene by semi-nested RT-PCR were sequenced. Software BioEdit 7.0.9.0 was used for sequence alignment, and software Mega 6.0 was used to construct the evolutionary tree. Results: In 72 samples, the detection rate of norovirus was 31.94% (23/72) by real-time RT-PCR, 38.89% (28/72) by semi-nested RT-PCR and 48.61% (35/72) by parallel test. The coincidence rate of the two methods was 73.61%, a moderate degree (Kappa value =0.43). A total of 13 norovirus strains were successfully sequenced, and 11 strains (7 GⅡ.17 strains, 2 GⅡ. 4 Sydney_ 2012 strains, 1 GⅡ. 1 strain and 1 GⅡ. 21 strain) were obtained from norovirus positive samples by two RT-PCR methods, two strains (1 GⅡ. 17 strain and 1 GⅡ. 3 strain) were obtained from real-time RT-PCR negative samples which were positive for norovirus by semi-nested RT-PCR. The similarity between these strains and reference strains from diarrhea patients, environmental sewage, and shellfish products were 84.4% - 100.0%. Conclusions: The parallel test of norovirus in oysters by two RT-PCR methods can improve the detection rate and detect more genotypes. Norovirus strains in oysters were highly homologous with reference strains from diarrheal patients, environmental sewage, and shellfish products. Therefore, surveillance, prevention and control for norovirus should be carried out in people who have frequent contacts with oysters and related environments.

Comparison of perioperative complications and oncological results of transanal total mesorectal excision and robot assisted total mesorectal excision / 国际外科学杂志

Objective:To explore the perioperative safety and oncological results of laparoscopic assisted transanal total mesorectal excision (TaTME) and robot assisted total mesorectal excision (TME) in radical resection of low rectal cancer.Methods:A single center retrospective study was conducted. Analyzed the clinical data of 54 patients with low rectal cancer who received robot assisted TME or laparoscopic assisted TaTME in the first hospital of Jilin University from January 2020 to July 2022, including 39 males and 15 females, with a median age of 61 years old. They were divided into robot assisted TME group ( n=29) and laparoscope assisted TaTME group ( n=25) according to the surgical methods. Follow-up was carried out through outpatient, telephone and wechat. The follow-up time was 30 days after operation. The quality of mesorectal excision was divided into high quality and low quality according to the evaluation of the integrity of the mesentery of the specimen after total mesorectal excision and the circumferential cutting edge. The primary outcome was the quality of mesorectal excision, and the secondary end points were surgery related information, postoperative pathological information, and postoperative complications. SPSS25.0 software was used for statistical analysis. The measurement data of skew distribution were expressed by M( Q1, Q3), and the Mann Whitney U test was used for comparison between groups. The counting data were expressed by n(%), and the comparison between groups was conducted by χ2 test or Fisher exact probability method. Results:The high-quality mesorectal excision rate in TaTME group was 88% (22 cases), and the high-quality mesorectal excision rate in robot group was 100%, with no statistical difference( χ2=3.69, P=0.093). The operation time of TaTME group and robot assisted TME group was [180 (165, 220)] min and [140 (117, 168)] min, respectively, with statistical significance ( U=125.00, P<0.001). The preventive ileostomy rate was 100% in the TaTME group and 37.9% in the robot group( χ2=23.27, P<0.001). Compared with TaTME group, robot assisted TME had a longer distance from the lower tumor to the distal cutting edge [10 (5, 25) mm vs 35 (21, 41) mm, U=117.00, P<0.001], a longer distance from the deepest tumor to the circumferential cutting edge [15 (10, 25) mm vs 25 (20, 34) mm, U=165.50, P=0.003], and a larger tumor maximum meridian [20 (4, 52) mm vs 42 (30, 48) mm, U=202.50, P=0.005]. The total incidence of complications within 30 days after operation was 16.7%, of which the incidence of Clavien-Dindo Ⅰ to Ⅱ complications was 11.1%, and the incidence of Clavien-Dindo ⅢA complications was 5.6%. The overall complication rate of TaTME group was higher, but there was no significant difference (20.0% vs 13.8%, χ2=0.37, P=0.718). Conclusion:Both TaTME and robot assisted TME can ensure good quality of TME operation and can be used as an effective and safe treatment for low rectal cancer. When performing TaTME surgery for low rectal cancer, it is more necessary to ensure sufficient distal margin distance.

Effect of Two Kinds of Compound Rhizosphere Growth-promoting Bacteria on Growth，Physiological Characteristics and Pharmacodynamic Components of Angelicae Sinensis Radix / 中国实验方剂学杂志

ObjectiveTo study the effects of foliar spraying of two kinds of compound rhizosphere growth-promoting agents on the growth and physiological characteristics of Angelicae Sinensis Radix （ASR）， as well as the pharmacodynamic components， in order to lay a foundation for providing functional microbial agents for ecological cultivation of ASR. MethodThe compound growth-promoting agents T1 （Pseudomonas CBS5， CBS7 and CBSB） and T2 （Bacillus 5C1， 5C5 and 5C7） with the concentration of 1×108 CFU·mL-1 were sprayed on the leaf surface of the field， and the sterile potato glucose broth medium was used as the control （CK）. The plant growth indexes of ASR were measured by conventional methods， the photosynthetic physiological indexes of ASR were measured by portable photosynthetic measurement system， the enzyme activities of plants and microorganisms were measured by kit method， and the endogenous hormone levels were analyzed by ultra-performance liquid chromatography tandem mass spectrometry. The contents of ferulic acid， senkyunolide I， coniferyl ferulate， senkyunolide A and Z-ligustilide were determined by high performance liquid chromatography. ResultCompared with CK， the two compound inoculants could promote the growth of ASR and increase the biomass， increase the leaf net photosynthetic rate， stomatal conductance， intercellular CO2 concentration， transpiration rate， increase catalase， peroxidase， superoxide dismutase， polyamine oxidase， diamine oxidase and polyphenol oxidase enzyme activities， increase endogenous jasmonic acid， cytokinin and gibberellin levels in plants， increase the contents of ferulic acid， senkyunolide A and Z-ligustilide， reduce the contents of malondialdehyde and abscisic acid， and reduce the incidence of root rot. ConclusionFoliar spraying of two kinds of rhizosphere compound growth-promoting agents can promote the growth， photosynthesis and stress resistance of ASR， and can improve the quality of ASR in different degrees. Comprehensive analysis shows that T1 treatment is better than T2 treatment in the growth-promoting and quality-enhancing of ASR.