Background::Histological healing is closely associated with improved long-term clinical outcomes and lowered relapses in patients with ulcerative colitis (UC). Here, we developed a novel diagnostic criterion for assessing histological healing in UC patients.Methods::We conducted a retrospective cohort study in UC patients, whose treatment was iteratively optimized to achieve mucosal healing at Shanghai Tenth People’s Hospital of Tongji University from January 2017 to May 2022. We identified an inflammatory cell enumeration index (ICEI) for assessing histological healing based on the proportions of eosinophils, CD177 + neutrophils, and CD40L + T cells in the colonic lamina propria under high power field (HPF), and the outcomes (risks of symptomatic relapses) of achieving histological remission vs. persistent histological inflammation using Kaplan-Meier curves. Intrareader reliability and inter-reader reliability were evaluated by each reader. The relationships to the changes in the Nancy index and the Geboes score were also assessed for responsiveness. The ICEI was further validated in a new cohort of UC patients from other nine university hospitals. Results::We developed an ICEI for clinical diagnosis of histological healing, i.e., Y = 1.701X 1 + 0.758X 2 + 1.347X 3 - 7.745 (X 1, X 2, and X 3 represent the proportions of CD177 + neutrophils, eosinophils, and CD40L + T cells, respectively, in the colonic lamina propria under HPF). The receiver operating characteristics curve (ROC) analysis revealed that Y <-0.391 was the cutoff value for the diagnosis of histological healing and that an area under the curve (AUC) was 0.942 (95% confidence interval [CI]: 0.905-0.979) with a sensitivity of 92.5% and a specificity of 83.6% ( P <0.001). The intraclass correlation coefficient (ICC) for the intrareader reliability was 0.855 (95% CI: 0.781-0.909), and ICEI had good inter-reader reliability of 0.832 (95% CI: 0.748-0.894). During an 18-month follow-up, patients with histological healing had a substantially better outcome compared with those with unachieved histological healing ( P <0.001) using ICEI. During a 12-month follow-up from other nine hospitals, patients with histological healing also had a lower risk of relapse than patients with unachieved histological healing. Conclusions::ICEI can be used to predict histological healing and identify patients with a risk of relapse 12 months and 18 months after clinical therapy. Therefore, ICEI provides a promising, simplified approach to monitor histological healing and to predict the prognosis of UC.Registration::Chinese Clinical Trial Registry, No. ChiCTR2300077792.

Objective: To investigate the expression changes of cyclin-dependent kinase inhibitor 3(CDKN3) indifferent tumors and its effect on tumor staging, prognosis and immunotherapy. Methods: The expression characteristics of CDKN3 in different cancers using data from TCGA, CCLE, ICGC, and GTEx databases were evaluated. The GEPIA2 platform and Kaplan-Meier analysis were utilized to assess the effect of CDKN3 on tumor pathological staging and survival prognosis. The TIMER platform was employed to explore the influence of CDKN3 on the tumor immune microenvironment and immunotherapy. Its effect on immune checkpoint and key immunotherapeutic predictors using bioinformatics methods was explored. The GeneMANIA tool was used to construct the protein-protein interaction(PPI) network of CDKN3. Kyoto Encyclopedia of Genes and Genomes(KEGG) and Gene Onotology(GO) enrichment analyses were conducted to explore the biological processes and signaling pathways associated with CDKN3. The effect of CDKN3 on HepG2 cell proliferation, invasion, migration, and apoptosis was validated through transfection with CDKN3 siRNA. Results: CDKN3 was found to be widely overexpressed in tumors. High expression of CDKN3 was often associated with advanced pathological staging and poor survival prognosis. CDKN3 expression was negatively correlated with most immune checkpoints and positively correlated with tumor mutation burden(TMB), microsatellite instability(MSI), and mismatch repair(MMR) genes. CDKN3 was associated with cell cycle, cellular senescence, and the p53 signaling pathway. Furthermore, EdU staining, JC-1 staining, Transwell, and Wound Healing assays confirmed that CDKN3 promoted HCC cell proliferation, invasion, and migration while inhibiting apoptosis. Conclusion Abnormal expression of CDKN3 is closely related to tumor staging, prognosis, and immune microenvironment characteristics, making it a potential prognostic marker and immunotherapy adjuvant target in cancer.

Objective:To evaluate the clinical efficacy and safety of endoscopic submucosal dissection (ESD) for early colorectal cancer and its precancerous lesions by using novel lifting clip-assisted traction.Methods:From March to July 2021, 42 patients with colorectal lesions who received ESD at the Digestive Endoscopy Center of Shanghai Tenth People's Hospital were included in the retrospective study. Nineteen patients were enrolled as the observation group using the novel lifting clip, and 23 others in the control group without the help of an auxiliary method. The operation time, the hospital stay, hospital expenses and the incidence of complications of the two groups were compared.Results:All 42 patients successfully received ESD. The operation time of the observation group was significantly shorter than that of the control group [31.00 (21.00, 58.00) min VS 60.00 (30.00, 75.00) min, Z=-2.04, P=0.04]. The postoperative hospital stay of the observation group was significantly shorter than that of the control group [2.00 (1.00, 2.00) d VS 2.00 (2.00, 3.00) d, Z=-1.99, P=0.04]. The hospital cost was lower than that of the control group, but the difference was not statistically significant (19 331.42 ± 3 481.20 yuan VS 19 802.40 ± 2 548.50 yuan, t=-0.49, P=0.63). No intraoperative perforation occurred in either group. There was no significant difference in intraoperative blood loss between the observation group and the control group [0.00 (0.00, 5.00) mL VS 3.00 (0.00, 7.00) mL, Z=-1.42, P=0.16]. There was 1 case of postoperative abdominal pain in the observation group, 2 cases of postoperative abdominal pain and 1 case of fever in the control group. There was no significant difference in the overall incidence of postoperative complications between the observation group and the control group [5.3% (1/19) VS 13.0% (3/23), χ2=0.73, P=0.39]. Conclusion:The novel lifting clip-assisted colorectal ESD is safe and effective, which can significantly shorten the ESD operation time and postoperative hospital stay without increasing the economic burden of patients.

Objective:To observe the effect of electroacupuncture (EA) on the expression of erythropoie-tin-producing hepatocyte receptor B2 (EphB2) in the cortex around the infracted area of middle cerebral artery occlusion (MCAO) rats at different timing, and to reveal the possible mechanism of acupuncture in the treatment of cerebral ischemia.
Methods:A total of 180 male Sprague-Dawley (SD) rats were randomly divided into a sham operation group, a model group, an acupoint group and a non-acupoint group, with 45 rats in each group. Rats in each group were further divided into three subgroups: postoperative 3 d, postoperative 14 d and postoperative 21 d groups, with 15 rats in each subgroup. The MCAO model was made by the modified occlusion method. The neurological function score, 2,3,5-triphenyl tetrazolium chloride (TTC) staining, immunohistochemistry assay, immunofluorescence double labeling method and Western blot were used to detect the corresponding indicators.
Results:The neurological impairment of rats was most obvious at postoperative 3 d, and then gradually improved with time, which was more significant in the acupoint group (P<0.05). The change of infarcted volume was consistent with the neurological function impairment. The number of EphB2 positive cells (EphB2+) around the infarcted area was decreased significantly at postoperative 3 d, and then gradually improved with time, which returned to the same level as that in the sham operation group at postoperative 21 d. The increase was most significant in the acupoint group (P<0.05), and the positive cell number was higher than that in the sham operation group (P<0.01). Western blot and immunohistochemistry results were basically consistent. Immunofluorescence displayed that EphB2+ and postsynaptic density-95 positive (PSD-95+) were co-expressed, after the MCAO operation, in the cortical neuron around the infracted area, and the number of co-expressing cells was increased gradually with time, which was most significant in the acupoint group (P<0.05).
Conclusion:Electroacupuncture at Ganshu (BL 18) and Shenshu (BL 23) can significantly improve the neurological function and cerebral infarcted volume ratio of MCAO rats, which may be related to the activation of EphB2 expression in cortex around the infracted area and the promotion of synaptic remodeling.

Objective To compare the cost-effectiveness of closed-loop versus open-loop infusion of propofol guided by bispectral index (BIS) in elderly patients undergoing abdominal surgery.Methods Sixty American Society of Anesthesiologists physical status Ⅱ patients of either sex,aged 65-75 yr,with body mass index of 18 25 kg/m2,undergoing elective open gastrointestinal tumor resection with general anesthesia,were allocated into closed-loop target-controlled infusion (TCI) group (group C) and open-loop TCI group (group O) using a random number table.Propofol was given using closed-loop TCI,and the target BIS value was set at 45-55 in group C.In group O,the target plasma concentration (2.0-3.5 μg/ml)of propofol was adjusted to maintain the BIS value at 45-55.Remifentanil was given by TCI with the target plasma concentration of 2-8 ng/ml in both groups.The total consumption of propofol and remifentanil,time rate of maintaining BIS value within the target range,development of intraoperative hypertension and hypotension,emergence time,tracheal extubation time,time for recovery of orientation,first ambulation time,time to first flatus and length of postoperative hospital stay were recorded.The development of nausea and vomiting and delirium within 3 days after operation and intraoperative awareness was recorded.The cost of anesthetics and total cost of anesthesia were calculated.Results Compared with group O,the total consumption of propofol was significantly decreased,the total consumption of remifentanil was increased,the time rate of maintaining BIS value within the target range was increased,the emergence time,tracheal extubation time and time for recovery of orientation were shortened,the cost of propofol and total cost of anesthesia were decreased (P＜0.05),and no significant change was found in the cost of remifentanil,incidence of postoperative delirium and nausea and vomiting,first ambulation time,time to first flatus or length of postoperative hospital stay in group C (P＞0.05).Intraoperative awareness was not found in two groups.Conclusion Compared with open-loop infusion of propofol guided by BIS,closed-loop infusion of propofol guided by BIS is a cost-effective method of anesthesia in elderly patients undergoing abdominal surgery.

Objective To investigate the clinical roles of lysine methyltransferase 5A(KMT5A)in human hepatocellular carcinoma(HCC)and its functions in cell migration and invasion. Methods The expression levels of KMT5A of 60 cases were detected by immunohistochemistry(IHC). KMT5A siRNA was used to down-regulate the expression of KMT5A in SMMC-7721 cells. Cell migration and invasion were measured by wound healing assays and transwell assays,respectively. Immunoblotting was used to detect the expression of MMP-2 after siRNA trans-fection. miR-186 mimics were transfected into SMMC-7721 cells and the mRNA levels of KMT5A was detected by qRT-PCR after transfection. Results High expression of KMT5A was associated with large tumor diameter (>5 cm,P=0.047)and advanced TNM stage(Ⅲ+Ⅳ,P=0.035). The expression of KMT5A was knocked down by siRNA in SMMC-7721 cells. Down-regulation of KMT5A suppressed cell migration(P=0.031,P=0.006)and invasion(P=0.010),and impaired MMP-2 expression(P=0.040). Overexpression of miR-186 could significantly inhibit the expression of KMT5A(P = 0.007). Conclusions Over-expression of KMT5A in HCC tissues associ-ates with poor clinical features. KMT5A knockdown inhibits the migration and invasion on HCC cells.

Objective To investigate the specimen source and gene phenotype of ESBLs in ESBLs-producing Klebsiella pneumonia of people′s hospital of Sanya city,so as to provide basis for clinical use of drugs and nosocomial infection.Methods Klebsiella pneumoniae was isolated from specimens during January 2013 to December 2014,bacteria identification and susceptibility tests were detected by Phoenix-100 system biochemical,supplementary susceptibility test was confined by K-B method according to 2014 CLSI standards.WHONET 5.6was used in the statistical analysis of all data.Results Totally 213 strains Klebsiella pneumoniae were isolated.The detection rates were 78.4％ of the respiratory secretions,8.92％ and 5.2％ respectively of the secretion and the midstream urine.The strains had a certain resistance to commonly used antimicrobial.The highest resistance rate was 98.1％ to cefotaxime,and the lowest resistance rate was 2.86％ to imipenem.There were 195 in 213 ESBLs producing Klebsiella pneumoniae strain were detect one or more drug resistance gene.The detecting rates of 6 p-lactamase gene of CMY,CTX,TEM,SHV,DHA1 and KPC were 6.10％,76.53％,59.62％,76.06％,12.21％ and 2.82％.Conclusion Klebsiella pneumoniae is mainly isolated from respiratory secretions in the hospital,has a certain resistance to commonly used antimicrobial.We should learn more about the distribution of resistance genes of ESBLs strains,improve the efficiency of the treatment of the infection and to control nosocomial infection and the incidence of multi-drug resistance.

Objective To evaluate the role of mitochondrial ATP-sensitive potassium(mito-KATP) channels in dexmedetomidine-induced attenuation of myocardial ischemia-reperfusion(I∕R)injury in rats. Methods Forty pathogen-free healthy male Sprague-Dawley rats, aged 8-12 weeks, weighing 200-350 g, were divided into 5 groups(n=8 each)using a random number table: sham operation group(group S), I∕R group, dexmedetomidine group(group DEX), a specific mito-KATPchannel blocker 5-hydroxyde-canoate(5-HD)group(group 5-HD)and dexmedetomidine plus 5-HD group(group DEX+5-HD). Myo-cardial I∕R was produced by occlusion of the anterior descending branch of the left coronary artery for 30 min followed by 120 min reperfusion in pentobarbital sodium-anesthetized rats. Dexmedetomidine 5 μg∕kg was intraperitoneally injected at 15 min prior to reperfusion in group DEX.5-HD 40 mg∕kg was intraperitoneally injected at 30 min prior to reperfusion in group 5-HD. In group DEX+5-HD, 5-HD 40 mg∕kg and dexme-detomidine 5 μg∕kg were intraperitoneally injected at 30 and 15 min prior to reperfusion, respectively. The parameters of cardiac function such as left ventricular systolic pressure(LVSP), left ventricular end-dias-tolic pressure(LVEDP)and the maximum rate of increase or decrease in left ventricular pressure(±dp∕dtmax)were recorded before ischemia(T0)and at 60 and 120 min of reperfusion(T1,2). Blood samples were collected from the carotid artery at the end of reperfusion for determination of the concentrations of cre-atine kinase-MB(CK-MB)and cardiac troponin I(cTnI)in serum. The animals were then sacrificed, and hearts were removed for determination of the myocardial infarct size in the left ventricular myocardial tissues. Results Compared with group S, the LVSP and ±dp∕dtmaxwere significantly decreased, and the LVEDP was increased at T1-2, and the concentrations of CK-MB and cTnI in serum and myocardial infarct size were increased in the other groups(P<0.05). Compared with group I∕R, the LVSP and ±dp∕dtmaxwere signifi-cantly increased, and the LVEDP was decreased at T1-2, and the concentrations of CK-MB and cTnI in ser-um and myocardial infarct size were decreased in group DEX, and the LVSP and ±dp∕dtmaxwere significant-ly increased at T1-2, the concentrations of CK-MB and cTnI in serum and myocardial infarct size were de-creased(P<0.05), and no significant change was found in LVEDP in group DEX+5-HD, and no signifi-cont change was found in the parameters mentioned above in group 5-HD(P>0.05). Compared with group DEX, the LVSP and ±dp∕dtmaxwere significantly decreased, and the LVEDP was increased at T1-2, and the concentrations of CK-MB and cTnI in serum and myocardial infarct size were increased in DEX+5-HD group(P<0.05). Conclusion The mechanism by which dexmedetomidine attenuates myocardial I∕R inju-ry is partially related to promotion of mito-KATPchannel opening in rats.

OBJECTIVETo investigate the association between receptor-interacting kinase protein 4 (RIPK4) relative copy number (RCN) and prognosis of stage III( colorectal cancer (CRC) patients treated with oxaliplatin-based chemotherapy.

METHODSRIPK4 RCN was determined by real-time PCR and then dichotomized into high RIPK4 RCN group(n=35) and low RIPK4 RCN group (n=104) using the third quartile as the cut-off point. Overall survival (OS) and recurrence-free survival (RFS) were compared between high and low RIPK4 RCN groups. The subgroup prognostic analysis was also conducted based on tumor site.

RESULTSThe median follow-up period was 49 months (ranged 4 to 98 months). Patients with high RIPK4 RCN had poorer OS than those with low RIPK4 RCN, which reached marginal significance(median OS, 43.0 months vs. 53.5 months, P=0.074). Meanwhile there was no significant difference of RFS between two groups (P=0.352). In colon cancer subgroup, high RIPK4 RCN was significantly associated with poor OS (median OS, 31.5 months vs. 56.6 months, P=0.015) but not with RFS (P=0.135). In rectal cancer subgroup, RIPK4 RCN was not associated with both OS and RFS (P=0.981, P=0.738). Multivariate analysis revealed that high RIPK4 RCN was an independent prognostic factor of OS in stage III( CRC patients treated with oxaliplatin-based chemotherapy (HR=2.903, 95% CI: 1.275 to 6.610).

CONCLUSIONRIPK4 RCN is significantly associated with OS in stage III( colon cancer patients receiving oxaliplatin-based chemotherapy and may be a novel biomarker that can predict the efficacy of oxaliplatin in colon cancer patients.

Objective To investigate the optimum ratio of medicine dosage for dexmedetomidine mixed with oxycodone used for patient-controlled intravenous analgesia (PCIA) after gastrointestinal surgery.Methods Eighty patients of both sexes, aged 35-64 yr, weighing 55-75 kg, of American Society of Anesthesiologists physical status Ⅰ or Ⅱ , undergoing elective gastrointestinal surgery, were randomly divided into 4 groups (n=20 each) using a random number table: oxycodone group (group O), and different ratios of medicine dosage when dexmedetomidine was added to sufentanil groups (OD1-3 groups).At 15 min before the end of surgery, oxycodone 0.1 mg/kg was injected intravenously, and PCIA pump was connected simultaneously.In group O, the PCIA solution contained oxycodone 1.00 mg/kg in 100 ml of normal saline.In group OD1, the PCIA solution contained oxycodone 1.00 mg/kg and dexmedetomidine 2.5 μg/kg in 100 ml of normal saline.In group OD2 , the PCIA solution contained oxycodone 0.75 mg/kg and dexmedetomidine 2.5 μg/kg in 100 ml of normal saline.In group OD3, the PCIA solution contained oxycodone 0.50 mg/kg and dexmedetomidine 2.5 μg/kg in 100 ml of normal saline.The PCIA pump was set up to deliver a 0.5 ml bolus dose with a 15-min lockout interval and background infusion at 2 ml/h.Oxycodone 0.05 mg/kg was injected intravenously as a rescue analgesic, and visual analogue scale score was maintained ≤ 4.The requirement for rescue analgesics was recorded.The requirement for the rescue analgesic was recorded within 48 h after surgery.The number of successfully delivered doses, and occurrence of adverse reactions such as bradyeardia, hypotension, nausea, vomiting, over-sedation, somnolence, pruritus, and respiratory depression were recorded.Patient's satisfaction with analgesia was recorded at 72 h after surgery.Results No patients required the rescue analgesic or developed over-sedation, vomiting, respiratory depression and hypotension in the four groups.Compared with group O, the incidence of somnolence was significantly increased in group OD1, the incidence of nausea, somnolence, bradycardia and pruritus was decreased in OD2 and OD3 groups, and the degree of patient's satisfaction with analgesia was increased in OD1-3 groups (P＜0.05).Compared with group OD1, the incidence of nausea, somnolence, bradycardia and pruritus was significantly decreased in OD2 and OD3 groups, the degree of patient's satisfaction with analgesia was increased in group OD3 (P＜0.05) , and no significant was found in the degree of patient's satisfaction with analgesia in group OD2 (P＞0.05).Compared with group OD2, no significant was found in the incidence of adverse reactions (P＞0.05) , and the degree of patient's satisfaction with analgesia was significantly decreased in group OD3 (P＜0.05).The number of successfully delivered doses was significantly larger in group OD3 than in O, OD1 and OD2 groups (P＜0.05).Conclusion Dexmedetomidine 2.5 μg/kg added to oxycodone 0.75 mg/kg is the optimum ratio of medicine dosage when used for PCIA after gastrointestinal surgery.