OBJECTIVE To systematically evaluate the relationship of semaglutide with malignant neoplasms in type 2 diabetes mellitus （T2DM） patients. METHODS Retrieved from the Cochrane Library， PubMed， Embase， ClinicalTrials.gov， CNKI， Wanfang data and CBM， randomized controlled trials （RCTs） about semaglutide in the treatment of T2DM patients with outcome measures including malignant tumor events were collected from the establishment of the database to June 2024. Meta- analysis was performed by using RevMan 5.3 software to assess the risk of malignant neoplasms. RESULTS A total of 24 RCTs （26 trials） involving 24 145 patients were included. Results of meta-analysis showed that compared to placebo， there was no statistical significance in the risk of semaglutide in pancreatic cancer [RR＝0.39， 95%CI（0.10， 1.50）， P＝0.17]， thyroid cancer [RR＝1.29， 95%CI（0.38， 4.36）， P＝0.68]， prostate cancer [RR＝1.05， 95%CI（0.36， 3.12）， P＝0.92]， skin cancer [RR＝1.27， 95%CI（0.80， 2.02）， P＝0.31]， gastrointestinal cancer [RR＝1.00， 95%CI（0.47， 2.14）， P＝1.00]， colorectal cancer [RR＝0.96， 95%CI（0.40， 2.26）， P＝0.92]， lung cancer [RR＝1.62， 95%CI（0.74， 3.55）， P＝0.23]， breast cancer [RR＝1.25， 95%CI（0.45， 3.51）， P＝0.67] or all malignant neoplasms [RR＝0.96， 95%CI（0.76， 1.21）， P＝0.73]. Compared to other antidiabetic drugs， there was no statistical significance in the risk of semaglutide in pancreatic cancer [RR＝0.62， 95%CI（0.18， 2.09）， P＝0.44]， thyroid cancer [RR＝1.09， 95%CI（0.25， 4.78）， P＝0.90]， prostate cancer [RR＝2.09， 95%CI（0.46， 9.47）， P＝0.34]， skin cancer [RR＝1.76， 95%CI（0.65， 4.72）， P＝0.26]， gastrointestinal cancer [RR＝0.68， 95%CI（0.19， 2.35）， P＝0.54]， colorectal cancer [RR＝0.60， 95%CI（0.20， 1.78）， P＝0.36]， lung cancer [RR＝1.00， 95%CI（0.24， 4.11）， P＝1.00]， breast cancer [RR＝0.82， 95%CI（0.25， 2.66）， P＝0.74] or all malignant neoplasms [RR＝1.36， 95%CI（0.96， 1.94）， P＝0.09]. CONCLUSIONS Semaglutide does not increase the risk of any type of malignant neoplasms in T2DM patients.

Radiation-induced intestinal injury is a radiation injury of the colon and rectum after radiotherapy for pelvic malignant tumors. This condition affects multiple organs in the pelvis, making treatment challenging. In clinical practice, the most effective protocol is often determined through discussion by a multi-disciplinary team (MDT). However, due to the severity and complexity of radiation enteritis, many patients still experience poor diagnosis and treatment outcomes. Holistic integrative management (HIM) is a rapidly developing concept that has greatly enhanced clinical medicine in recent years. It improves the level of diagnosis, treatment, prevention, and rehabilitation from multiple dimensions of prevention, screening, diagnosis, treatment, and rehabilitation. In the context of radiation-induced intestinal injury, HIM also calls for the implementation of an individualized management system that focuses on the patient as a whole within the healthcare team. From the perspective of HIM, this article introduces some of the latest progress of radiation-induced intestinal injury in recent years.

Radiation-induced intestinal injury is a radiation injury of the colon and rectum after radiotherapy for pelvic malignant tumors. This condition affects multiple organs in the pelvis, making treatment challenging. In clinical practice, the most effective protocol is often determined through discussion by a multi-disciplinary team (MDT). However, due to the severity and complexity of radiation enteritis, many patients still experience poor diagnosis and treatment outcomes. Holistic integrative management (HIM) is a rapidly developing concept that has greatly enhanced clinical medicine in recent years. It improves the level of diagnosis, treatment, prevention, and rehabilitation from multiple dimensions of prevention, screening, diagnosis, treatment, and rehabilitation. In the context of radiation-induced intestinal injury, HIM also calls for the implementation of an individualized management system that focuses on the patient as a whole within the healthcare team. From the perspective of HIM, this article introduces some of the latest progress of radiation-induced intestinal injury in recent years.

Alfalfa(Medicago sativa L.)is the most important legume forage crop worldwide with high nutritional value and yield.For a long time,the breeding of alfalfa was hampered by lacking reliable information on the autotetraploid genome and molecular markers linked to important agro-nomic traits.We herein reported the de novo assembly of the allele-aware chromosome-level genome of Zhongmu-4,a cultivar widely cultivated in China,and a comprehensive database of genomic variations based on resequencing of 220 germplasms.Approximate 2.74 Gb contigs(N50 of 2.06 Mb),accounting for 88.39％of the estimated genome,were assembled,and 2.56 Gb contigs were anchored to 32 pseudo-chromosomes.A total of 34,922 allelic genes were identified from the allele-aware genome.We observed the expansion of gene families,especially those related to the nitrogen metabolism,and the increase of repetitive elements including transposable elements,which probably resulted in the increase of Zhongmu-4 genome compared with Medicago truncatula.Population structure analysis revealed that the accessions from Asia and South America had rela-tively lower genetic diversity than those from Europe,suggesting that geography may influence alfalfa genetic divergence during local adaption.Genome-wide association studies identified 101 sin-gle nucleotide polymorphisms(SNPs)associated with 27 agronomic traits.Two candidate genes were predicted to be correlated with fall dormancy and salt response.We believe that the allele-aware chromosome-level genome sequence of Zhongmu-4 combined with the resequencing data of the diverse alfalfa germplasms will facilitate genetic research and genomics-assisted breeding in variety improvement of alfalfa.

Objective:To screen the neutralizing epitope of enterovirus 71 (EV71) and determine the specific minimum amino acid sequence that triggers immunity for providing a theoretical basis for the development of synthetic peptide vaccines.Methods:EV71 neutralizing antibody-specific binding clones were panned and sequenced using a phage display random 12-peptide library to obtain the key sequences of neutralizing epitopes. A series of peptides containing the key sequences with N-terminal acetylation (AC) and C-terminal linking to Keyhole limpet hemocyanin (KLH) were synthesized. Serum samples were collected after immunizing mice with the modified peptides. Then the immunogenicity of the peptides and the neutralizing activity of serum samples were analyzed by Western blot, ELISA and neutralization test.Results:After three rounds of panning, cloning and sequencing, KQEKDL was identified as the key motif. The serum samples collected from the mice immunized with the modified series of peptides containing key motifs had different degrees of binding ability to EV71 and VP1 protein. The serum samples of mice immunized the synthetic peptide containing only the minimum key motif (AC-KQEKDL-KLH) had the strongest response to the other three peptides and EV71 and the highest neutralizing titer.Conclusions:The EV71 neutralizing epitope was successfully screened using the phage display random peptide library. The key motif of KQEKDL might be the specific minimum amino acid sequence that triggered the immune system. This study provides a theoretical basis for better understanding the immune response mechanism, evaluating the immunogenicity of the antigens and further research and development of polypeptide vaccines.

Objective: To evaluate whether simultaneous vaccination with live attenuated polio vaccine affects the immunogenicity of live attenuated rotavirus (RV) vaccine. Methods: Rotarix produced by GlaxoSmithKline was used as the research object. Two doses of Rotarix were orally administered on day 0 and month 1, and oral live attenuated polio vaccine (OPV) was administered on day 0, month 1 and month 2 according to the national vaccination plan. Healthy infants aged 6 to 16 weeks were randomly divided into two groups: interval vaccination group (Rotarix and OPV were vaccinated on different days) and simultaneous vaccination group (Rotarix and OPV were vaccinated on the same day). Serum samples were collected on day 0, month 2 and month 12, and serum RV-IgA was measured by enzyme linked immunosorbent assay. Statistical analysis was performed to evaluate whether there were statistical differences in the seroconversion rate and level distribution of RV-IgA between the two groups. Results: The seroconversion rate of serum RV-IgA in month 2 was 73.84% in the interval vaccination and 63.95% in the simultaneous vaccination group, and the difference between them was statistically significant (P<0.05). The geometric mean concentrations (GMC) of RV-IgA were 97 EU/ml and 90 EU/ml, respectively (P>0.05). Compared with the simultaneous vaccination group, the seroconversion rate and GMC of serum RV-IgA in month 12 were higher in the interval vaccination group, and the differences were statistically significant (P<0.05). Conclusions Simultaneous vaccination with live attenuated polio vaccine would affect the immune response of live attenuated rotavirus vaccine, especially the maintenance of RV-IgA antibody level.

Objective To systemically review andquantify the incidence of oral feeding intolerance in acute pancreatitis. Methods Randomized controlled trials that reported the oral feeding intolerance rates of acute pancreatitis were searchedfrom PubMed, EMBASE, Medline, Cochrane Library, WanFang, CNKI, CMCC and VIP dal,abase wilh the" Acute pancreatitis " " Feeding intolerance" " Incidence" " Meta- analysis "from January 2002 to May 2017. Date were analyzed by using R 3. 4. 0 software. The heterogeneity of data were analyzed using 12test. Results Eleven randomized controlled trials including 658 cases were enrolled in Meta-analysis. The incidence of oral feeding of intolerance was 12. 2% . The result of subgroup analysis showed that there were no significant difference in the incidence of oral feeding intolerance when region, sample size and published year were taken into analysis (P > 0. 05). The oral feeding intolerance rate of mild acute pancreatitis was lower than that when moderately severe acute pancreatitis and severe acute pancreatitis were, included (8. 2% and 19. 9% , respectively; P = 0. 002 7). Conclusion Oral feeding intolerance affects approximately l in 8 patients with acute pancreatitis. The incidence of oral feeding intolerance of patients with severe acute pancreatitis is higher than that of patients with mild acute pancreatitis

Gastrointestinal fistula patients may suffer from complicated intra-abdominal infection and sepsis with improper treatment, which is characterized by high mortality ranging from 20% to 60%, as well as high medical costs. Gastrointestinal fistula patients with complicated intra-abdominal infections are not often diagnosed early, and proper treatment remains an unsolved problem. Therefore it is a great challenge for surgeons to repair broken intestines under complicated intra-abdominal infection conditions and to repair ruptured intestines under conditions of severe abdominal adhesions and swelling of the intestinal wall and mesentery. After the open abdominal approach was first adopted to treat complicated intra-abdominal infection patients by Duff and Moffat in 1981, it gradually began to be used more widely. However, some investigators have reported that the open abdomen approach has not been effective in controlling controlled mortality, instead, it may even increase mortality. For this reason, the approach has only been used in large medical centers rather than having been widely popularized. In this review, the effect, timing, indications of open abdomen approach and the principles for the open abdominal wound management are summarized, and the reason for the various efficacy among different centers is also analyzed. We provide a new perspective for clinicians to manage the gastrointestinal fistula patients with complicated intra-abdominal infection.
Abdominal Cavity ; surgery ; Digestive System Fistula ; surgery ; Humans ; Intraabdominal Infections ; surgery ; Sepsis ; surgery

Objective To explore the role of cell apoptosis pathway in alcoholic pancreatitis.Methods C57BL/J mice were divided into control group (NC) and Alcohol group (AC),Acute pancreatitis group (AP) and Alcoholic acute pancreatitis group(AAP).Alcohol treatment was 10％ w/v ethanol feeding for 2 d,15％ w/v ethanol for 5 d,and then 20％ w/v ethanol until 13 weeks.AP model was established by the intraperitoneal injection of 50μg caerulein/kg body weight once an hour for a total of 7 times.Blood samples were collected for detecting serum amylase and lipase activity.Part pancreatic tissue was collected and the wet and dry weight were both measured to calculate the water content.The routine pathological exanination of the pancreatic tissues were conducted.The expression of apoptosis associated protein caspase3 and caspase8 was determined by Western blot.And cell apoptosis was determined using TUNNEL method.Results The level of serum amylase in NC group,AC group,AP group and AAP group were(3 630 ± 259),(3 196 ± 187),(35 955 ± 4607) and (53 607 ± 3 848) U/L;the level of serum lipase were (502 ± 41),(745 ± 42),(7 346 ± 665) and(12 764 ± 2 544) U/L;the water content were (70.2 ± 3.1) ％,(69.6 ± 2.0) ％,(78.2 ± 1.5) ％ and(85.0 ± 3.0) ％ and (12.75 ± 0.25);the expression of caspase3 were (1.017 ± 0.0784),(1.287 ± 0.097),(178 ± 0.07785) and (0.2443 ± 0.0243);the expression of caspase8 were (0.8289 ± 0.0096),(0.5985 ±0.0735),(1.27 ±0.08) and (0.145 ±0.015);the number of apoptotic cells were 1,6,214,97/10 high power field.The pathological score of pancreas injure in NC group,AC group,AP group and AAP group were 0,0,(7 ± 0.4) and (12.8 ± 0.3),respectively.Serum anylase,lipase,water content and pathological scores in AP group were obviously higher than those in NC group (P ＜ 0.05),which in AAP group were also obviously higher than those in AP group,and all the differences were statistically significant (all P ＜0.05).Compared with NC group,the expressions of apoptosis associated protein caspase3 and caspase8 and the number of apoptotic cells were obviously increased in AP group,which were obviously higher than those in AAP group,but the expression of caspase3 and caspase8 in AAP group were decreased compared with NC group,and all the differences were statistically significant (all P ＜ 0.05).Conclusions Chronic alcohol exposure may aggravate the severity of pancreatitis,and the inhibition of apoptosis pathway and the enhancement of acinar cell necrosis may be involved in this process.

Objective To investigate the role of transcriptional-coactivator with PDZ-binding motif( TAZ) in genistein-induced osteoblastogenic differentiation of mouse bone marrow-derived mesenchymal stem cells ( BMSCs) .Methods Mouse BMSCs were cultured in phenol red-freeα-MEM containing osteogenic supplements for inducing osteogenic differentiation.BMSCs were transfected with siRNA-TAZ and treated with genistein.The temporal sequence of osteoblastic differentiation in BMSCs cultures was assayed by measuring alkaline phosphatase activity (ALP) and calcium deposition.The mRNA expression of bone sialoprotein ( BSP) and osteocalcin ( OC) were detected by reverse transcription-polymerase chain reaction(RT-PCR).The binding interaction between TAZ and cbfa1 was identified by co-immunoprecipitation.Results TAZ expression was detected during the induction of osteogenic differentiation, the ALP activity and calcium deposition were significantly decreased in BMSCs which were transfected with siRNA-TAZ.Genistein(0.01-1 μmol/L) exhibited a dose-dependent effect on TAZ expression in mouse BMSCs cultures.Treatment with genistein ( 1 μmol/L ) resulted in increased ALP avtivity and calcium deposition of BMSC cultures as function of time.Genistein(1μmol/L) also promoted the nuclear localization of TAZ and augmented the interaction between TAZ and cbfa1, and by which upregulated cbfa1-mediated gene expression such as BSP and OC.However, the ALP avtivity and calcium deposition, as well as the expression of BSP and OC were not promoted by genistein in BMSCs transfected with siRNA-TAZ.Conclusion These data suggest that the TAZ plays an important role in genistein-induced osteoblastic differentiation of mouse BMSCs cultures.