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 investigate the cell death-inducing effect of methyl rosmarinate (MR) on human hepatoma Hep-3B and SK-Hep1 cells and their potential mechanisms. 【Methods】 The effects of MR on the viability of Hep-3B, SK-Hep1 and MIHA cells were determined by cell counting kit-8 (CCK-8) assay. The morphological changes of three kinds of cells treated with different concentrations of MR were observed by optical microscopy. EdU assay and flow cytometry were used to detect the proliferation and apoptosis of Hep-3B and SK-Hep1 cells. Transwell assay was used to study the effects of MR on the migration and invasion of Hep-3B and SK-Hep1 cells. Western blotting was used to evaluate the protein expression levels of apoptosis, EMT and Akt/mTOR signaling pathways. 【Results】 After treated with different concentrations of MR (0~200 μmol/L) for 48 h, Hep-3B and SK-Hep1 cells activities were significantly decreased in a concentration-dependent manner (P<0.01), while there was no significant effect on MIHA cell activity (P>0.05), and the IC50 of Hep-3B and SK-Hep1 cells were 102.5 and 99.3 μmol/L, respectively. MR treatment (0-150 μmol/L) significantly inhibited the proliferation of Hep-3B and SK-Hep1 cells (P<0.05), while cell detachment and shrinkage were observed by optical microscopy on the Hep-3B and SK-Hep1 cells, while the morphology of MIHA cells was not changed. Compared with the control group, MR (100, 150 μmol/L) induced apoptosis in Hep-3B and SK-Hep1 cells, the expression levels of the pro-apoptotic proteins Bax and cleaved PARP were significantly increased (P<0.05), while the expression level of the anti-apoptotic protein Bcl-2 was significantly decreased (P<0.05). MR (100, 150 μmol/L) also inhibited the migration and invasion of HCC cells, significantly increased the expression of E-cadherin and decreased the expression of N-cadherin and Vimentin compared with the control group (P<0.05). Finally, Western blotting results showed that the expressions of p-Akt and p-mTOR in Hep-3B and SK-Hep1 treated by MR were significantly reduced in a dose-dependent manner, suggesting that MR may play an anti-cancer role by inhibiting Akt/mTOR signaling pathway. 【Conclusion】 MR can promote apoptosis in Hep-3B and SK-Hep1 cells, which may be closely related to the inhibition of Akt/mTOR signaling pathway.

Objective:To investigate the therapeutic effect and potential molecular mechanisms of cyclin-dependent kinase inhibitor-73 (CDKI-73), the Rab11 inhibitor, on liver fibrosis.Methods:Human LX2 cells were divided into four groups: negative control group, transforming growth factor-β (TGF-β) group, CDKI-73 group and TGF-β+ CDKI-73 group. Fifteen 5-week-old female C57 mice with body weight of (18.04±0.62) g were divided into 3 groups with 5 mice in each group: control group (intraperitoneal injection of olive oil + vehicle gavage), carbon tetrachloride (CCl 4) group (intraperitoneal injection of CCl 4 + vehicle gavage) and CCl 4+ CDKI-73 group (intraperitoneal injection of CCl 4+ CDKI-73 gavage). Another 15 5-week-old female C57 mice with body weight of (18.06±0.34) g were divided into 3 groups with 5 mice in each group: sham operation group (Sham), bile duct ligation (BDL) group + vehicle group (BDL+ vehicle gavage) and bile duct ligation+ CDKI-73 group (BDL+ CDKI-73 gavage). The expression of α-smooth muscle actin (α-SMA) and fibronectin(FN)in LX2 cells were analyzed by Western blot. Masson and Sirius red were used to examine the liver fibrosis after CDKI-73 treatment in vivo. Immunohistochemistry (IHC) was utilized to examine the expression of α-SMA in mice liver. Results:Collagen content assessed by Sirius red and Masson staining and α-SMA expression evaluated by IHC were all increased in CCl 4 group compared with control group ( q=38.47, 24.99, 36.79). Moreover, the collagen content and α-SMA expression in CCl 4 + CDKI-73 treatment group were obviously decreased compared with CCl 4 group ( q=24.72, 14.87, 27.50), and the differences were statistically significant (all P<0.001). Compared with Sham group, collagen content and α-SMA expression in bile duct ligation group were increased ( q=28.23, 41.01, 44.16). Furthermore, in BDL group, after treatment with CDKI-73, the collagen content and α-SMA expression were notably decreased ( q=22.88, 34.31 and 33.97, all P<0.001). Consistent with in vivo results, the relative expression levels of α-SMA and FN protein in TGF-β group were higher than those in TGF-β+ CDKI-73 group (α-SMA: 3.71±0.34 vs. 1.28±0.31; FN: 3.21±0.39 vs. 0.83±0.06, all P<0.001). The mRNA relative expression levels of α-SMA and FN in TGF-β group were higher than those in TGF-β+ CDKI-73 group, and the differences were statistically significant ( P<0.001). However, the relative expression of TGF-β receptor Ⅱ protein in CDKI-73 group was higher than those in negative control group (4.68±0.63 vs. 1.00±0.22, P=0.004). The relative expression level of phosphorylated SMAD2 in TGF-β+ CDKI-73 group was lower than those in TGF-β group (1.67±0.24 vs. 3.99±0.44, P<0.001). Transwell assay showed that 0.5 μmol/L CDKI-73 could effectively inhibit the migration of LX2 cells, and the inhibitory ability became stronger with the increase of CDKI-73 concentration. Conclusion:CDKI-73 can inhibit the activation of hepatic stellate cells and liver fibrosis by inhibiting Rab11-dependent TGF-β signaling pathway both in vivo and in vitro.

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 investigate the benefits and risks of stress ulcer prevention (SUP) using proton pump inhibitors (PPI) for critical patients. Methods The clinical data of adult critically ill patients admitted to the intensive care unit (ICU) of Northern Jiangsu People's Hospital from January 2016 to December 2018 were retrospectively analyzed. All patients who were treated with PPI for SUP within the first 48 hours after ICU admission were enrolled in the SUP group. Those who not received PPI were enrolled in the control group. A one-to-one propensity score matching (PSM) was performed to control for potential biases. The gender, age, underlying diseases, main diagnosis of ICU, drug use before ICU admission, sequential organ failure score (SOFA) at ICU admission, risk factors of stress ulcer (SU) and PPI usage were recorded. The end point was the incidence of gastrointestinal bleeding, hospital acquired pneumonia, Clostridium difficile infection and 30-day mortality. Kaplan-Meier survival curves were plotted, and survival analysis was performed using the log-rank test. Results 1 972 critical patients (788 in the SUP group and 1 184 in the control group) were enrolled, and each group enrolled 358 patients after PSM. Prior to PSM, compared with the control group, the SUP group had older patients, more underlying diseases, higher proportion of acute coronary syndrome (ACS), acute cerebrovascular disease, acute exacerbation of chronic obstructive pulmonary disease (AECOPD) and poisoning in main diagnosis of ICU, more serious illness, and more risk factors of SU, indicating that ICU physicians were more likely to prescribe SUP for these patients. The incidence of gastrointestinal bleeding in the SUP group was significantly lower than that in the control group [1.8% (14/788) vs. 3.7% (44/1 184), P < 0.05], while the incidence of hospital acquired pneumonia and 30-day mortality were significantly higher than those in the control group [6.6% (52/788) vs. 3.5% (42/1 184), 17.9% (141/788) vs. 13.1% (155/1 184), both P < 0.01]. There was no significant difference in the incidence of Clostridium difficile infection between the SUP group and the control group [2.9% (23/788) vs. 1.8% (21/1 184), P >0.05]. After the propensity scores for age, underlying diseases, severity of illness and SU risk factors were matched, there was no significant difference in the incidence of gastrointestinal bleeding or 30-day mortality between the SUP group and the control group [2.2% (8/358) vs. 3.4% (12/358), 15.9% (57/358) vs. 13.7% (49/358), both P > 0.05], but the incidence of hospital acquired pneumonia in the SUP group was still significantly higher than that in the control group [6.7% (24/358) vs. 3.1% (11/358), P < 0.05]. Kaplan-Meier survival curve analysis showed that the 30-day cumulative survival rate of the SUP group was significantly lower than that of the control group before the PSM (log-rank test: χ2 = 9.224, P = 0.002). There was no significant difference in the 30-day cumulative survival rate between the two groups after PSM (log-rank test: χ2 = 0.773, P = 0.379). Conclusion For critical patients, the use of PPI for SUP could not significantly reduce the incidence of gastrointestinal bleeding and mortality, but increase the risk of hospital acquired pneumonia.

Objective To study the influence of capecitabine or S-1 combined with oxaliplatin on the quality of life and serum tumor marker in gastric cancer patients with postoperative recurrence and metastasis.Methods One hundred and six cases of postoperative recurrence and metastasis treated by gastric cancer radical operation in our hospital from January 2013 to December 2015were selected and divided into the control group and observation group according to the random number table method,53 cases in each group.The control group was given S-1 combined with oxaliplatin treatment,while the experimental group was given capeeitabine combined with oxaliplatin treatment.The clinical efficacy,quality of life,serum related tumor markers and adverse reactions were compared between the two groups.Results The effective rate was 64.15％ in the control group and 69.81％ in the observation group,the difference was not statistically significant (P＜0.05).The improvement rate of the quality of life in the control group was 73.58％,the stability rate was 18.87％ and decline rate was 26.42％,the total improvement rate was 73.58％,which in the observation group were 49.06 ％,20.75 ％,30.19 ％ and 69.81 ％ respectively,the differences were not statistically significant (P＞0.05).After treatment,the levels of CA50,CA125,CA199 and CEA in the two groups were significantly decreased compared with before treatment (P＜0.05),but the serum related tumor markers had no statistically significant difference between the two groups (P＞0.05).The common adverse reactions in the two groups included hemoglobin decrease,white blood cell decline,thrombocytopenia,nausea and vomiting,the two groups could be tolerated,the difference was not statistically significant (P＞0.05).Conclusion Capecitabine or S-1 combined with oxaliplatin has the same curative effect in treating postoperative recurrence and metastasis after gastric cancer operation,the improvement of quality of life and serum related tumor indicators is similar,and the adverse reactions could be tolerated.

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 observe the clinical curative effect of NB -UVB combined with prednisone on neuralgia following herpes zoster .Methods 84 patients with neuralgia following herpes zoster were randomly divided into treatment group and control group , with 42 in each.The treatment group were given NB -UVB 3 times weekly, and oral prednisone tablet 10mg three times daily for 14 days.The control group was treated with prednisone tablet 10mg three times and indomethacin 25 mg two times daily for 14 days.The visual analogue scale (VAS) was used to evaluate the therapeutic effects in the two groups .Results The effective rate of the treatment group was 88.1%, and that of the control group was 69.05%.The therapeutic effect in the treatment group was statistically significant higher than that of the control group (χ2 =5.974, p=0.015).No marked side effects were observed in both groups .Con-clusion NB-UVB combined with prednisone is effect in the treatment of neuralgia following herpes zostert .

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.

Objective:To study the rule of spontaneous behavior and to explore the effect on emotion of mice peripherally infected with influenza A WSN33 virus( H1N1).Methods: Mice were intranasal inoculated with H1N1 WSN33 or saline.Then mice bodyweight change,and total distance movement,average movement speed distance in the central area and feces in the open field test in 5 minutes were recorded in two weeks.Results: Mice following WSN33 infection bodyweight declined sharply until day 7 post-inoculation,and mice bodyweight recovered from influenza infection at day 8 post-inoculation.Total distance movement of mice following H1N1 WSN33 infection decreased in the open field test,and difference of the reduction was significant from day 5 to day 10 post-inocu-lation.The average movement speed had no statistical difference.The range of numbers of fecal grains was large, and they were no significant difference.Conclusion:The total distance movement decreased,but average movement speed did not change following mice infected with H1N1 WSN33.They told us that mice infected with H1N1 WSN33 had anxiety,depressed and nervous emotion which is more evident in acute stage and early recovery stage,whereas the change of the nervous emotion was small and not obvious.