Although immunotherapy has made a breakthrough in the treatment of cancer,the emergence of drug resistance has limited be-nefits in most patients,and reversing immunotherapy resistance remains a hotly debated and unresolved issue.The tumor microenviron-ment(TME)comprises a large number of T lymphocytes.During the biological processes of proliferation,activation,and the effect of tumor-infiltrating lymphocytes(TILs),TILs face severe local metabolic stress,resulting in metabolic reprogramming to meet the markedly increased energy demand and biosynthesis requirements.This process of adaptive changes in the metabolic pattern is closely related to the pheno-type and function of TILs,affecting immunotherapy efficacy and mediating immunotherapy resistance.In recent years,with the study of TIL metabolism and the search for specific metabolic regulatory points,targeting the TIL metabolic pathway could restore the tumor-killing func-tion and reverse immunotherapy resistance.This review explores the relationship between the metabolic reprogramming of TILs and im-mune resistance,and provides a new strategy for reversing immune resistance.

Objective To introduce the robotic-assisted left hemicolectomy and Soave procedure and its clinical outcome for Hirschsprung's allied disease.Methods From June 2015 to November 2022,19 cases diagnosed with Hirschsprung's allied disease underwent left colectomy and Soave pull-through by using the da Vinci surgical system,and the clinical data of 19 children were summarized and analyzed.A four trocar technique was used.The left colon was firstly mobilized by laparoscopy from splenic flexure of colon to the level of peritoneal reflection,then the rectum was mobilized by Robotic system to the level of dentate line.A circumferential incision was made in the mucosa at 0.5 cm proximal to the dentate line.The upward submucosal dissection was carried out for approximately 1-2 cm.The left colon was pulled through the anal canal and resected.The coloanal anastomosis was fashioned manually 0.5 cm above the dentate line.21 cases underwent conventional laparoscopic-assisted Soave surgery were used as control group.Results All patients were successfully operated.Compared with conventional laparoscopic-assisted Soave surgery,the operation time was significantly prolonged(P＜0.01),the intraoperative blood loss was significantly reduced(P＜0.01),and the overall postoperative complication rate was significantly reduced(11％VS.43％,P＜0.05).There were no serious complications such as major bleeding and death.Conclusion Robotic-assisted left hemicolectomy and Soave procedure are safe and feasible in the treatment of Hirschsprung's allied disease,with few postoperative complications and satisfactory clinical outcome.

Objective:To compare the differences in the prevalence of mild micro-hepatic encephalopathy (MHE) among patients with cirrhosis by using the psychometric hepatic encephalopathy score (PHES) and the Stroop smartphone application (Encephal App) test.Methods:This prospective, multi-center, real-world study was initiated by the National Clinical Medical Research Center for Infectious Diseases and the Portal Hypertension Alliance and registered with International ClinicalTrials.gov (NCT05140837). 354 cases of cirrhosis were enrolled in 19 hospitals across the country. PHES (including digital connection tests A and B, digital symbol tests, trajectory drawing tests, and serial management tests) and the Stroop test were conducted in all of them. PHES was differentiated using standard diagnostic criteria established by the two studies in China and South Korea. The Stroop test was evaluated based on the criteria of the research and development team. The impact of different diagnostic standards or methods on the incidence of MHE in patients with cirrhosis was analyzed. Data between groups were differentiated using the t-test, Mann-Whitney U test, and χ2 test. A kappa test was used to compare the consistency between groups. Results:After PHES, the prevalence of MHE among 354 cases of cirrhosis was 78.53% and 15.25%, respectively, based on Chinese research standards and Korean research normal value standards. However, the prevalence of MHE was 56.78% based on the Stroop test, and the differences in pairwise comparisons among the three groups were statistically significant (kappa = -0.064, P < 0.001). Stratified analysis revealed that the MHE prevalence in three groups of patients with Child-Pugh classes A, B, and C was 74.14%, 83.33%, and 88.24%, respectively, according to the normal value standards of Chinese researchers, while the MHE prevalence rates in three groups of patients with Child-Pugh classes A, B, and C were 8.29%, 23.53%, and 38.24%, respectively, according to the normal value standards of Korean researchers. Furthermore, the prevalence rates of MHE in the three groups of patients with Child-Pugh grades A, B, and C were 52.68%, 58.82%, and 73.53%, respectively, according to the Stroop test standard. However, among the results of each diagnostic standard, the prevalence of MHE showed an increasing trend with an increasing Child-Pugh grade. Further comparison demonstrated that the scores obtained by the number connection test A and the number symbol test were consistent according to the normal value standards of the two studies in China and South Korea ( Z = -0.982, -1.702; P = 0.326, 0.089), while the other three sub-tests had significant differences ( P < 0.001). Conclusion:The prevalence rate of MHE in the cirrhotic population is high, but the prevalence of MHE obtained by using different diagnostic criteria or methods varies greatly. Therefore, in line with the current changes in demographics and disease spectrum, it is necessary to enroll a larger sample size of a healthy population as a control. Moreover, the establishment of more reliable diagnostic scoring criteria will serve as a basis for obtaining accurate MHE incidence and formulating diagnosis and treatment strategies in cirrhotic populations.

Objective To understand the status of new coronavirus contamination in the biosafety laboratory environment, identify key areas prone to contamination, and provide evidence for disinfection of central objects. Methods surfaces of high-frequency contact environment and protective equipment were sampled with moistened sterile cotton swabs after experiment and before disinfection, the results of the one-step real-time reverse transcription polymerase chain reaction (RT-PCR) of open reading frame 1ab and N fragment were used to evaluate the pollution status. Results Environmental surveys found 4 of 217 samples of environmental objects to be positive for new coronavirus RNA, that positive rate was 1.84%. Among them, BSL-3, BSL-2, and BSL-1 were sampled 23, 184, and 10 respectively. The 3 positive samples were from surfaces of nucleic acid extraction room of BSL-2 and from the handles of pass-through box, laboratory door handles and the outer surface of the alcohol watering pot respectively. The 1 positive sample was from the forearm of the protective clothing in BSL-2 laboratory. Conclusion There was a certain degree of virus pollution in key areas of the new coronavirus laboratory. The BSL-2 laboratory has a higher risk of environmental pollution than the BSL-3 and BSL-1 laboratories.

Objective To investigate the impact of pooling of inactivated samples on testing results of nucleic acid detection of SARS-CoV-2, and to provide a scientific detection scheme for the SARS-CoV-2 nucleic acid screening of large population samples. Methods The SARS-CoV-2 positive throat swab samples and the negative throat swab samples were inactivated at 56°C for 30 minutes, and mixed according to the ratio of positive samples to negative samples at 1:4, 1:9, and 1:19, respectively. Real-time fluorescent RT-PCR technology was used to detect the ORF-lab and N genes in the original solution and mixed solution. Results The nucleic acid test results of the 20 groups of inactivated samples were all positive. The nucleic acid test results of the 1:5 mixture and the 1:10 mixture were also positive. One group of samples of the 1:20 mixture was negative for ORF-lab and positive for the N gene. The Ct values of nucleic acid detection among all groups were significantly correlated. There was no statistically significant difference in the positive rate between different sample groups. Compared with the original solution, the Ct values of the ORF-lab gene of 1:5 mixture, 1:10 mixture, and 1:20 mixture samples increased by 1.73, 2.86, and 4.05, respectively, while the Ct values of the N gene of 1:5 mixture, 1:10 mixture and 1:20 mixture samples increased by 1.69, 2.79, and 3.25, respectively. Conclusion When conducting nucleic acid screening for SARS-CoV-2 in large population samples, a mixed test of less than 10 inactivated samples would not affect the qualitative results in most cases, but the results of weak positive samples may be affected.

OBJECTIVE:To systematically review the efficacy and safety of Xiaoke pill versus glibenclamide in the treatment of type 2 diabetes mellitus,and provide evidence-based reference for clinical treatment. METHODS:Retrieved from Medline, PubMed,EMBase,Cochrane Library,CBM,CJFD,Wanfang Database and VIP Database,randomized controlled trials (RCT) about the Xiaoke pill(test group)versus glibenclamide(control group)in the treatment of type 2 diabetes mellitus were enrolled. Meta-analysis was performed by using Rev Man 5.2 software after document selection,data extract and quality assessment by Co-chrane systematical evaluation. RESULTS:A total of 15 RCT were included,involving 3 319 patients. Results of Meta-analysis showed the hemoglobin A1c (HbA1c) level [MD=-0.39,95%CI(-0.75,-0.02),P=0.04],fasting plasma glucose (FPG) level [MD=-0.70,95%CI(-1.27,-0.12),P=0.02],2 h PG[MD=-0.87,95%CI(-1.55,-0.20),P=0.01],incidence of thirst with desire for drinks [RR=3.35,95%CI(1.92,5.85),P<0.001],incidence of tiredness and debilitation[RR=5.74,95%CI(3.52, 9.36),P<0.001] and incidence of hypoglycemia [RR=0.67,95%CI(0.49,0.91),P=0.01] in test group were significantly lower than control group,the differences were statistically significant. CONCLUSIONS:Xiaoke pill has better efficacy and safety than glibenclamide in the treatment of type 2 diabetes mellitus,can obviously improve the HbA1c,FPG,2 h PG tevel and TCM symp-toms.

Objective To obtain the peptide mass fingerprintings(PMF)of serums of the patients with bone metastasis and with-out metastasis and to filtrate and identify the differential serum proteins of patients with bone metastasis after radical mastectomy . To establish diagnostic models for diagnosis of bone metastasis after breast cancer operation .Methods Two groups of serum sam-ples were analyzed by ClinprotTM MALDI-TOF MS and gain PMF ,18 samples from patients with merely bone metastasis and 18 samples from patients without metastasis .Characteristic protein peaks were analyzed and selected by analyses software within Clin-prot system .Every group was repeated 2 times .Results All serum samples were repeated after 5 days and the fingerprintings were similar to the former .4 protein peaks were selected randomly to compute coefficient of variation which are less than 30% .The Clin-prot system has excellent repeatability .No differential protein was detected by analyzing PMF (P>0 .05) .Conclusion No differen-tial serum protein exists in patients with bone metastasis and without metastasis and detecting differential protein in peripheral blood may be impossible .

Objective To evaluate the clinical value of stereotactic radiotherapy for the treatment of metastatic hepatic carcino-ma .Methods 42 patients with metastatic hepatic carcinoma (metastases≤3 ,maximum tumor diameter≤5 cm)were treated with Co60 stereotactic radiotherapy alone .The prescription isodose of PTV was 3 .5-4 .5 Gy ,total 10 times ,the median survival time ,lo-cal control ,complication and RILD(radiation-induced liver disease) of the patients were assessed .Results The median survival date was 7 .9 months ,2 cases were complete remission ,the local control rates was 69% ,27 cases were partial remission ,and there was no serious adverse side effect ,such as severe radiation-induced hepatic injury .Conclusion The stereotactic radiotherqpy was a good choice for inoperable metastatic hepatic carcinoma .

A total of 100 HIN1 flu real-time-PCR positive throat swabs collected from fever patients in Zhejiang,Hubei and Guangdong between June and November 2009,were provided by local CDC laboratories.After MDCK cell culture,57 Influenza A Pandemic (H1N1) viruses were isolated and submitted for whole genome sequencing.A total of 39 HA sequences,52 NA sequences,36 PB2 sequences,31 PB1 sequences,40 PA sequences,48 NP sequences,51 MP sequences and 36 NS sequences were obtained,including 20 whole genome sequences.Sequence comparison revealed they shared a high degree of homology (96％～99％) with known epidemic strains (A/Califomia/04/2009(H1N1).Phylogenetic analysis showed that although the sequences were highly conserved,they clustered into a small number of groups with only a few distinct strains.Site analysis revealed three substitutions at loop 220 (221-228) of the HA receptor binding site in the 39 HA sequences:A/Hubei/86/2009 PKVRDQEG→PKVRDQEA,A/Zhejiang/08/2009 PKVRDQEG→PKVRDQER,A/Hubei/75/2009PKVRDQEG→PKVRDQGG,the A/Hubei/75/2009 was isolated from an acute case,while the other two were from patients with mild symptoms.Other key sites such as 119,274,292 and 294 amino acids of NA protein,627 of PB2 protein were conserved.Meanwhile,all the M2 protein sequences possessed the Ser32Asn mutation,suggesting that these viruses were resistant to adamantanes.Comparison of these sequences with other H1N1 viruses collected from the NCBI database provides insight into H1N1 transmission and circulation patterns.

Objective To inwst the antagonistic effect of thrombopoietin on adriamycin induced myocardium injury in rats and explore the mechanism.Methods 32 Wistar rats were randomized into four groups(n=8):Control group,ADM group,ADM+TPOL group and ADM+TPOH group.All agents were given by intraperitoneal injection.The control group was given saline.While the other three groups were given adriamycin at the dosage of20mg/kg.TPO group were injected TPO at the dosages of 10μg/kg or 30μg/kg three times on alternale days.ELISA was used to detect the concentration of CK-MB and cTnI in the serum of rats.The change of cardiocyte ultrastructure was observed by the electron microscope,and pathological change Was observed by immunohistochemistry staining.The expression level of 8- hydroxy-2'-deoxyguanosin(8-OHdG)produced by DNA oxidative damage in myocard tissue were detected.IPP6.0 software was used to detect IOD and calculate the 8-OHdG index.Results The energy of CK-MB and cTNI of TPO group was obviously lower than that in ADM group(P<0.01).The ultragtrueture of cardiocyte in the ADM group Wag damaged more severely than that in TPO group.Pathological Score,IOD and 8-OHdG index of TPO groups were lower than ADM group(P<0.05).These indexes had no significant statistics difference between ADM+TPOL group and ADM+TPOH group.Conclusions TPO can provide heart protection by antagonizing oxidative damage of myocardial cell induced by edriamycin.