In the past 30 years, gastrointestinal surgery in China has made significant progress, which is reflected in the gradual standardization of clinical diagnosis and treatment, significant improvement in surgical quality, improvement in short-term and long-term postoperative outcomes, and continuous development of high-quality clinical research. At present, the spectrum of disease in gastrointestinal surgery has changed from traditional benign diseases to malignant diseases represented by gastric cancer and colorectal cancer, metabolic diseases represented by obesity and diabetes, and immune diseases represented by inflammatory bowel disease. It is necessary to carry out full-cycle management for patients. In the new era full of opportunities and challenges, surgeons must be driven by innovation in surgical technology, guided by high-quality clinical research and guaranteed by standardized diagnosis and treatment of diseases, to continue to promote the high-quality development of gastrointestinal surgery in China.

Objective:To analyze the clinical phenotype and genetic characteristics for a child with Canavan disease.Methods:A child who was admitted to the Children's Hospital Affiliated to Shandong University on April 9, 2021 for inability to uphold his head for 2 months and increased muscle tone for one week was subjected to whole exome sequencing, and candidate variants were verified by Sanger sequencing.Results:Genetic testing revealed that the child has harbored compound heterozygous variants of the ASPA gene, including a paternally derived c. 556_559dupGTTC (p. L187Rfs*5) and a maternally derived c.919delA (p. S307Vfs*24). Based on the guidelines from the American College of Medical Genetics and Genomics, both variants were predicted to be pathogenic (PVS1+ PM2_Supporting+ PM3). Conclusion:The c. 556_559dupGTTC (p.L187Rfs*5) and c. 919delA (p.S307Vfs*24) compound heterozygous variants of the ASPA gene probably underlay the pathogenesis of Canavan disease in this child.

Objective:To explore the clinical and genetic features of two Chinese pedigrees affected with Autosomal dominant intellectual developmental disorder 49 (MRD49).Methods:Two MRD49 pedigrees which were admitted to the Children′s Hospital Affiliated to Shandong University respectively on January 28, 2021 and November 10, 2022 were selected as the study subjects. Clinical data of the two pedigrees were collected and analyzed. Genomic DNA was extracted from peripheral blood samples of the probands and their family members. The probands were subjected to mutational analysis by high-throughput sequencing. Candidate variants were validated using real-time fluorescence quantitative PCR (q-PCR) or Sanger sequencing and bioinformatic analysis. This study was approved by the Medical Ethics Committee of the Children′s Hospital Affiliated to Shandong University (No. SDFE-IRB/T-2022002).Results:Proband 1 had presented with language delay, motor retardation and intellectual disability, and his maternal grandmother, mother, aunt and cousin all had various degrees of intellectual disability. Sequencing results showed that proband 1 had deletion of exons 3 ~ 7 of the TRIP12 gene. q-PCR verification showed that his mother, aunt, maternal grandmother and cousin had all harbored the same deletion. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the variant was classified as pathogenic (PVS1+ PM2_Supporting+ PP1). Proband 2, who had mainly presented with language delay, motor retardation and intellectual disability, and was found to harbor a heterozygous c.3010C>T (p.Arg1004*) variant of the TRIP12 gene, which was verified to be de novo in origin. Based on the guidelines from the ACMG, the variant was classified as pathogenic (PVS1+ PS2+ PM2_Supporting). Conclusion:This study had diagnosed two MRD49 families through high-throughput sequencing. Above findings have enriched the phenotypic and mutational spectrum of MRD49 in China, which has also facilitated genetic counseling for the two pedigrees.

OBJECTIVE To evaluate the effects of ABCB1 genotypes on the efficacy and safety of taxanes in the treatment of breast cancer. METHODS By searching Embase，the Cochrane Library， PubMed， CNKI， and Wanfang databases， cohort studies and case-control studies about taxanes in the treatment of breast cancer were collected from the establishment of the database to July 2023. After screeningliterature， extracting data and evaluating quality， meta-analysis was performed by using RevMan 5.3 software. RESULTS A total of 11 studies were included， involving 1 321 patients. There was no correlation between the three genotypes and effective rate， the incidence of myelosuppression， the incidence of neurotoxicity （except for the allele and recessive model of ABCB1 C1236T）， and the incidence of hypersensitivity reactions （P＞0.05）. The subgroup analysis showed that there was a correlation between ABCB1 C1236T dominant model and effective rate when using anthracyclines+5-fluorouracil+cyclophosphamide+taxanes （P＜0.05）， there was a correlation between ABCB1 C3435T recessive model and effective rate when using taxanes+trastuzumab （P＜0.05）. ABCB1 C1236T allele model and recessive model were correlated with sample size ≥100 and using cyclophosphamide+epirubicin+5- fluorouracil+paclitaxel or cyclophosphamide+epirubicin+paclitaxel+trastuzumab or cyclophosphamide+epirubicin+5-fluorouracil+ trastuzumab+paclitaxel regimens； recessive model with sample size ＜100 and the African region were correlated with the incidence of peripheral neuropathy； recessive model was correlated with cutaneous adverse reactions （P＜0.05）. ABCB1 C3435T recessive model was correlated with the incidence of reduced neutrophil count with sample size ≥100； the incidence of white blood cell count reduction with sample size ＜100 and using docetaxel+epirubicin+cyclophosphamide was correlated with both the allele model and the dominant model； the incidence of infections was correlated with the dominant model （P＜0.05）. The incidence of neutrophil count reduction with the sample size ＜100 was correlated with allele model of ABCB1 G2677T/A； the incidence of edema with sample size ≥100 was correlated with allele model and recessive model； the incidence of infection was correlated with allele model and dominant model， especially in patients with neutrophil count complicated with fever （P＜0.05）. CONCLUSIONS ABCB1 genotypes are not correlated with effective rate of taxanes in the treatment of breast cancer， but ABCB1 C3435T genotype is associated with decreased neutrophil counts， decreased white blood cell counts and infections； ABCB1 C1236T genotype is associated with neurotoxicity and cutaneous adverse reactions； ABCB1 G2677T/A genotype is associated with decreased neutrophil counts， infections， and edema.

Objective To retrospectively analyze the efficacy and safety of low-dose antithymocyte globulin(ATG)combined with low-dose post transplantation cyclophosphamide(PTCY)in prevention of graft versus host disease(GVHD)after haploidentical transplantation.Methods Clinical data of 90 patients receiving haplotype matched transplantation in No.920 Hospital of PLA Joint Logistic Support Force from January 2022 to February 2023 were collected,and they were divided into study group(n=47)and control group(n=43)according to different GVHD prevention programs.The patients of the study group were given low-dose ATG combined with low-dose PTCY,and those of the control group received standard dose of PTCY.The implantation status,occurrence of GVHD,survival status and other indicators were analyzed between the 2 groups.Results ① Both groups of patients were successfully implanted,the median duration for neutrophil implantation(11 vs 17 d,P＜0.05)and platelet implantation(12 vs 20 d,P＜0.05)was significantly shorter in the study group than the control group.The incidence of grade Ⅱ～Ⅳ aGVHD(12.8％vs 34.9％,P＜0.05)and grade Ⅲ～Ⅳ aGVHD(6.4％ vs 20.9％,P＜0.05)was significantly lower in the study group than the control group,so was the non-recurrent mortality rate(6.4％vs 20.9％,P＜0.05)and the incidence of hemorrhagic cystitis(12.8％ vs 34.9％,P＜0.05).② By the end of the study,there were no significant differences in the incidence of mild and moderate and severe cGVHD,recurrence rate,reactivation rates of EBV and CMV,overall survival rate or progression-free survival rate between the 2 groups.Conclusion For haploidentical transplantation,low-dose ATG combined with low-dose PTCY has the advantages of lower incidence of GVHD,non-recurrent mortality,incidence of hemorrhagic cystitis and faster implantation.

Objective To preliminarily explore the efficacy of chimeric antigen receptor T cells(CAR-T)targeting CD 123 in the treatment of acute myeloid leukemia(AML)and the role of dasatinib in the treatment of CD123 targeting CAR-T induced side effects.Methods Clinical data of 1 patient with relapsed AML admitted to No.920 Hospital of PLA Joint Logistic Support Force in September,2019 were collected.The patient relapsed after previous multi-line chemotherapy and was treated with CD123 targeting CAR-T therapy.The routine blood changes of the patient after treatment were observed.Dasatinib was used when agranulocytosis occurred,40 mg orally 3 times per day,and was stopped when agranulocytosis was relieved.Changes in blood cells,CAR-T amplification,and disease control were observed.The patient was followed up for over 1 year.Results Flow cytometry for bone marrow showed that minimal residual disease negative result was observed in 30 d after infusion.The patient remained disease-free for over 1 year.After CD 123 CAR-T cells infusion,significant expansion of CAR-T cells was observed,accompanied by granulocyte deficiency and cytokine release syndrome(CRS).After using dasatinib,inhibition of CAR-T cell expansion was observed,accompanied by blood cell recovery,and CRS symptoms were alleviated.After stop of dasatinib,CAR-T cells expanded again and blood cells decreased again.Conclusion CAR-T cells targeting CD 123 have certain efficacy in the treatment for relapsed AML.Dashatinib has a blocking effect on the amplification and function of CAR-T,which can alleviate bone marrow suppression caused by CD 123 targeting CAR-T and avoid severe CRS.

Objective:To analyze the research hotspots of self-management in patients with chronic obstructive pulmonary disease (COPD) at home and abroad.Methods:Related literature on self-management of COPD patients were searched in China National Knowledge Infrastructure and Web of Science databases, and the searched period was from January 1, 2013 to June 30, 2023. CiteSpace 5.8 software was used for keyword cluster analysis.Results:A total of 641 articles in Chinese and 1 192 in English were obtained. Domestic research hotspots about self-management of COPD patients mainly focused on health education, continuing care, rehabilitation care, etc. Foreign research hotspots about self-management of COPD patients mainly focused on mobile health, telemedicine and so on.Conclusions:This paper analyzes the research hotspots of self-management of COPD patients at home and abroad and provides reference for future research on self-management of COPD patients.

Objective To evaluate the efficacy and safety of eravacycline in the treatment of complicated intra-abdominal infection(cIAI)in Chinese adult patients.Methods In this multicenter,randomized,double-blind phase Ⅲ study,cIAI patients were randomly assigned to receive either eravacycline(1.0 mg/kg,q12h)or ertapenem(1 g,q24h)by intravenous infusion for 5 to 14 days.The primary and secondary efficacy endpoints included the clinical efficacy and microbiological efficacy in different populations,including modified intention-to-treat(MITT)population,clinically evaluable(CE)population,and microbiologically evaluable(ME)population,at different time points after treatment.Clinical cure rates at specific visits were summarized and compared between treatment groups in different populations.The microbial eradication rate was calculated for the patients with baseline pathogens.The incidence of adverse events(AE)and drug-related treatment emergent adverse event(TEAE)was analyzed by treatment group.Results A total of 144 patients with cIAI who received at least one dose of the study drug were included in the MITT population.The clinical cure rate was 77.8％(56/72)in eravacycline-treated patients and 90.3％(65/72)in ertapenem-treated patients at 25-31 days after the first dose(TOC visit).When the patients who received insufficient treatment(＜72 hours)were excluded,the clinical cure rate was 83.6％(56/67)in eravacycline group and 90.3％(65/72)in ertapenem.For CE and ME patients,the clinical cure rate at TOC visit was 91.1％(51/56)and 83.3％(25/30)in eravacycline group,95.3％(61/64)and 90.9％(30/33)in ertapenem group.Eravacycline treatment achieved microbiological eradication rate of 91.3％(21/23)against Escherichia coli at TOC visit in micro-MITT population while ertapenem treatment resulted in a microbiological eradication rate of 96.2％(25/26).The microbiological efficacy of eravacycline and ertapenem against Klebsiella pneumoniae was 4/5 and 3/3,respectively.The incidence of TEAE was similar in eravacycline and ertapenem groups(75.0％vs.70.8％),most of which were mild or moderate.The AEs associated with eravacycline were mainly infusion site phlebitis(9.7％,7/72)and infusion site pain(8.3％,6/72).Conclusions Similar to ertapenem,eravacycline has good clinical and microbiological efficacy in treating cIAI.It is also safe and well-tolerated in the patients.

Objective:To retrieve, evaluate, and summarize the best domestic and international evidence on non-pharmacological management of sleep disorders in breast cancer patients undergoing chemotherapy, providing evidence-based guidance for healthcare professionals to conduct standardized assessment and management of sleep disorders in these patients.Methods:Clinical questions were translated into evidence-based questions using the PIPOST model. A systematic search of domestic and international databases and professional association websites was conducted for literature related to non-pharmacological management of sleep disorders in breast cancer patients undergoing chemotherapy, including clinical decisions, evidence summaries, guidelines, and systematic reviews. The search covered publications up to December 17, 2022. Two researchers trained in evidence-based nursing independently completed the quality assessment, evidence extraction, and summary of the included literature.Results:A total of 16 publications were included, comprising two clinical decisions, one evidence summary, five guidelines, six systematic reviews, and two randomized controlled studies. The best evidence was summarized from seven aspects: multidisciplinary collaboration, identification of risk factors, assessment and monitoring, referral, psychological behavioral interventions, exercise management, and complementary therapies, resulting in 25 key recommendations.Conclusions:This study summarizes the current best evidence for non-pharmacological management of sleep disorders in breast cancer patients undergoing chemotherapy. Healthcare professionals can follow these best evidence practices to standardize the assessment of patient sleep disorder symptoms and choose appropriate intervention plans based on clinical context and patient preferences, thereby improving patient sleep quality.

Three novel,highly oxygenated polyketides,multioketides A-C(1-3),and three previously described multioxidized aromatic polyketides(4-6),were isolated from an endophytic Penicillium sp.YUD17006 associated with Gastrodia elata.Their chem-ical structures were elucidated using extensive spectroscopic data,electronic circular dichroism calculations,and single X-ray diffrac-tion analysis.All metabolites were characterized by a typical α,β-unsaturated ketone fragment and exhibited a high degree of oxidation.Multioketides A and B were identified as a pair of epimers featuring a rare dihydroisobenzofuranone core.Multioketide C possessed a novel 5/6/6/6 heterotetracyclic chemical architecture with unusual 1,4-dioxin functionalities.Plausible biosynthetic pathways for 1-6 were proposed.Additionally,compound 3 demonstrated weak inhibitory activities against both acetylcholinesterase and protein tyr-osine phosphatase 1B.