Background:When colonic adenoma involves diverticulum,inflammation in the diverticulum will increase the risk of adenomatous dysplasia.Therefore,patients with colonic diverticulum adenoma are at a higher risk of colon cancer,and the adenoma needs to be resected to avoid poor outcome and improve prognosis.Aims:To explore the efficacy and safety of endoscopic mucosal resection(EMR)in treatment of colonic diverticulum adenoma.Methods:Fourteen consecutive cases of colonic adenoma near or involving a diverticulum treated by EMR from Jun.2018 to Jan.2022 at the First People's Hospital of Hangzhou Lin'an District were collected,and their clinical characteristics and outcomes were analyzed.The primary outcome was complications,including bleeding,perforation,and electrocoagulation syndrome,while the secondary outcomes were the en bloc resection rate,complete resection rate and local recurrence rate.Results:Among the 14 patients with colonic diverticulum adenoma,13 were type A(near a diverticulum)while 1 was type B(involving a diverticulum).The diameter of the lesion was(0.76±0.25)cm,and the operation time was(19.67±5.33)minutes.The main histological type was tubular adenoma,and the pathological results was intraepithelial neoplasia in most of the cases.Delayed hemorrhage was observed in 1 patient(7.1%),and electrocoagulation syndrome in 1 patient(7.1%).No perforation event occurred.The en bloc resection rate and complete resection rate were 100%.Ten patients accepted reexamination of colonoscopy within 1 year after surgery,and no local recurrence was found.Conclusions:EMR is safe and effective for treatment of colonic diverticulum adenoma.However,patients using antiplatelet drugs and adenoma involving both appendiceal orifice and diverticulum should be alert to postoperative complications.

Background:Early diagnosis and treatment can effectively improve the prognosis of colon cancer.Simple,effective and sensitive screening indicators are of great significance for identification of early cancer and precancerous lesions.L-selectin is a cell adhesion molecule,and podocalyxin(PODXL)is its ligand,both of them play key roles in the development of cancer.Aims:To investigate the expression and significance of L-selectin and its ligand PODXL in colon cancer.Methods:A total of 120 cases of pathological specimens(40 hyperplastic polyp,40 colon adenoma,and 40 colon cancer)from Nov.2020 to Nov.2022 at the Frist People's Hospital of Hangzhou Lin'an District and the First Affiliated Hospital of Zhejiang Chinese Medical University were collected,and 20 cases of normal intestinal mucosal tissue were served as controls.qRT-PCR and immunohistochemistry were used to detect the mRNA and protein expressions of L-selectin and PODXL,respectively.Western blotting was used to determine the expressions of L-selectin and PODXL,and their relations with different clinicopathological parameters of colon cancer were analyzed.In addition,60 serum specimens of colon cancer were collected.ELISA was used to detect serum concentrations of L-selectin and PODXL.Results:Expressions of L-selectin and PODXL mRNA and protein in colon adenoma group were significantly higher than those in normal controls and hyperplastic polyp group(P<0.05),and mRNA and protein expressions of L-selectin and PODXL in colon cancer group were significantly higher than those in normal controls,hyperplastic polyp group and colon adenoma group(P<0.05).Significant differences in protein expressions of L-selectin and PODXL were found in different pathological types,lymph node metastasis,Dukes staging in colon cancer(P<0.05).Expression of L-selectin was positive correlated with expression of PODXL in colon cancer(r=0.855,P<0.001).Serum concentrations of L-selectin and PODXL were significantly lower in the initial group than in the relapse group(P<0.05),and serum concentrations of L-selection and PODXL was significantly lower in the non-metastatic group than in the metastatic group(P<0.05).Serum concentrations of L-selectin and PODXL at 3 months after surgery was significantly lower than 3 days after surgery and before surgery(P<0.05).Conclusions:L-selectin and PODXL may be involved in the development and progression of colon cancer.They are carcinogenic proteins,and their detection could provide reference value for the prevention and early diagnosis of colon cancer,and through early screening of lesion could improve the prognosis of colon cancer to a certain extent.

Background:Studies have confirmed that colorectal tumors may be caused by normal mucosa near or inside the diverticulum,and patients with colon diverticulum are more likely to develop colon cancer than those without diverticulum.When colorectal adenoma involves diverticulum,the inflammatory state in the diverticulum will increase the risk of adenomatous dysplasia.Therefore,adenomas involving colon diverticulum are more likely to develop malignant changes,and adenomas involving colon diverticulum need to be resected to avoid colon cancer outcomes.Improved prognosis.Aims:To explore the efficacy and safety of endoscopic mucosal resection(EMR)treatment of colorectal tumors near or involving a diverticulum.Methods:Fourteen consecutive cases of adenoma(near or involving a diverticulum)during EMR treatment from Jun.2018 to Jan.2022 were collected,and analyze their clinical characteristics and outcomes.The main outcomes were adverse events,including bleeding,perforation,and electrocoagulation syndrome,while the secondary outcome was the total resection rate,block resection rate and local recurrence rate.Results:Among the 14 patients with colon adenoma,1 case was inside the diverticulum,13 cases were near the diverticulum,the diameter of the lesion was(0.76±0.25)cm,the operation time was(19.6±5.33)min.The main tissue types were tubular adenomas,and the pathologic characteristics were low grade intraepithelial neoplasia.Among the complications,delayed hemorrhage was found in 1 case(7.1%),the patient had a history of taking antiplatelet drugs(clopidogrel),electrocoagulation syndrome was found in 1 case(7.1%),and appendiceal orifice and diverticulum were involved in this patient,with no perforation event.The whole resection rate and the complete resection rate were 100%(14/14).Within 1 year after surgery,10 patients came to the hospital for re-examination of colonoscopy,and no local recurrence was found.Conclusions:EMR treatment involving colonic diverticulum adenoma is safe and effective.However,patients with adenoma involving antiplatelet drugs and appendiceal orifice and diverticulum should be alert to postoperative complications.

Objective:To investigate the efficacy of CT imaging features in evaluating occult peritoneal metastasis (OPM) of diffuse infiltrating gastric cancer (Borrmann Type Ⅳ).Methods:Totally 101 patients with locally advanced Borrmann type Ⅳ gastric cancer were retrospectively collected who were admitted to Peking University Cancer Hospital from March 2014 to March 2021. The patients were divided into OPM group (53 cases) and the non-OPM group (48 cases) according to the results of preoperative CT and laparoscopic exploration/peritoneal cytology examination. The pathological examination results were recorded, including the degree of histological differentiation and Lauren classification. The evaluation indicators included the tumor center position, the number of tumor-occupied portions, involved orientation, mucosal broadband sign, stratified enhancement, serosa invasion, increased density of peripheral fat tissue, and enlarged lymph nodes. The maximum thickness of the primary tumor, average CT value of the primary tumor (arterial phase, venous phase, and delayed phase), difference between venous phase and arterial phase, difference between delayed phase and venous phase, and pattern of the enhanced curve were recorded. The Mann-Whitney U or Chi-square test was used to compare the differences of pathological and CT features between two groups. The multivariate logistic regression was used to screen independent predictors and establish a nomogram. The receiver operating characteristic curve was used to evaluate the performance of the nomogram in predicting OPM, and the Hosmer-Lemeshow test was used to test the model′s goodness of fit. Results:There was statistical significance in the seven indicators between the OPM and non-OPM groups, including tumor-occupied portions of stomach, mucosal broadband sign, stratified enhancement, serosa invasion, increased density of peripheral fat tissue, the enhanced curve pattern and the degree of histological differentiation ( P<0.05). Among them, the degree of histological differentiation (OR=0.19, P=0.033), stratified enhancement (OR=7.02, P=0.005) and serosa invasion (OR=14.27, P<0.001) were independent predictors of OPM. The nomogram was established based on the three significant features. The area under the curve for predicting OPM was 0.826 (95%CI 0.745-0.908), the sensitivity was 0.566 and the specificity was 0.938. The Hosmer-Lemeshow test showed a good agreement between the OPM risk predicted by the nomogram and the actual risk ( P=0.525). Conclusions:The CT features of Borrmann type Ⅳgastric cancer complicated with OPM have specific characteristics. The diagnosis model based on the degree of histological differentiation, stratified enhancement, and serosa invasion had high efficacy in evaluating OPM.

Objective:To investigate the protective mechanism of TAK242, a specific inhibitor of Toll-like receptor 4 (TLR4), on the liver of septic rats.Methods:Eighteen male Sprague-Dawley (SD) rats were randomly divided into three groups ( n = 6 in each group). The septic model was established by intraperitoneal injection of lipopolysaccharide (LPS) 15 mg/kg. The rats in the TAK242 intervention group received intraperitoneal injection of TAK242 (5 mg/kg) before modeling, while the rats in the septic model group and the control group were injected with the same amount of solvent [10% dimethyl sulfoxide (DMSO) + 90% corn oil]. Six hours later, the blood of abdominal aorta was collected and the levels of serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were measured by enzyme linked immunosorbent assay (ELISA). The rats were sacrificed to obtain liver, the expression levels of TLR4, tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), cysteinyl aspartate-specific proteinase-3 (caspase-3), nuclear factor-κB p65 (NF-κB p65) and phosphorylated NF-κB p65 (p-NF-κB p65) were detected by Western blotting. Immunohistochemical staining was used to observe NF-κB p65 protein expression in liver, and hepatocyte injury was assessed by hematoxylin-eosin (HE) staining. Results:Serum ALT and AST levels in the septic model group were significantly higher than those in the control group [ALT (μg/L): 26.639±7.814 vs. 2.847±2.150, AST (μg/L): 28.442±8.417 vs. 5.779±3.019, both P < 0.01]. The ALT and AST levels in the TAK242 intervention group were significantly lower than those in septic model group [ALT (μg/L): 7.269±3.398 vs. 26.639±7.814, AST (μg/L): 3.580±3.115 vs. 28.442±8.417, both P < 0.01]. Light microscopy showed that the hepatocytes in the septic model group were disordered, with obvious cell edema and increased inflammatory cells infiltration; the hepatocytes in the TAK242 intervention group were more neatly arranged, with significantly reduced hepatocyte edema and reduced inflammatory cells infiltration. Western blotting results showed that caspase-3 protein expression in hepatic tissue of septic model group was significantly higher than that in the control group (caspase-3/GAPDH: 0.794±0.164 vs. 0.482±0.055, P < 0.05), and caspase-3 protein expression in the TAK242 intervention group significantly decreased than that in the septic model group (caspase-3/GAPDH: 0.482±0.056 vs. 0.794±0.164, P < 0.05), which indicated that TAK242 could attenuate hepatocytes apoptosis of septic rats. The expression of IL-6, TNF-α and TLR4 protein and the ratio of p-NF-κB p65/NF-κB p65 in hepatic tissue of septic model group were significantly higher than those in control group (IL-6/GAPDH: 1.442±0.204 vs. 1.019±0.024, TNF-α/GAPDH: 1.089±0.098 vs. 0.806±0.005, TLR4/GAPDH: 1.292±0.085 vs. 0.941±0.087, p-NF-κB p65/NF-κB p65 ratio: 1.936±0.081 vs. 1.579±0.183, all P < 0.05), IL-6, TNF-α and TLR4 protein expression and p-NF-κB p65/NF-κB p65 ratio in the TAK242 intervention group were significantly lower than those in septic model group (IL-6/GAPDH: 1.035±0.042 vs. 1.442±0.204, TNF-α/GAPDH: 0.572±0.096 vs. 1.089±0.098, TLR4/GAPDH: 0.984±0.078 vs. 1.292±0.085, p-NF-κB p65/NF-κB p65 ratio: 1.484±0.255 vs. 1.936±0.081, all P < 0.05), it is suggested that LPS-induced sepsis could activate the inflammatory response mediated by TLR4/NF-κB pathway in liver, and the activation of TLR4/NF-κB pathway was inhibited by TAK242 through the TLR4 pathway, therefore, the inflammation of liver in septic rats was reduced. Immunohistochemical staining showed that the positive expression of NF-κB p65 in liver was significantly increased in the septic model group compared with the control group; the positive expression of NF-κB p65 was significantly reduced in the TAK242 intervention group compared with the septic model group, and there was almost no positive expression in the nucleus. Conclusion:TAK242 could reduce liver function injury and protect the liver by inhibition TLR4/NF-κB pathway in septic rats.

Objective:To construct an Internet + linkage model based on medical alliance and evaluate its implementation effect.Methods:From October 2020 to June 2021, convenience sampling was used to select 132 patients with malignant tumors who were treated with peripherally inserted central catheters (PICC) chemotherapy and discharged with catheters in Chongming Branch of Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine. The 67 patients who returned to the PICC outpatient clinic of Chongming Branch, Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine during the treatment interval for PICC maintenance were set as the control group, and the routine maintenance method was adopted. A total of 65 patients who chose maintenance points near their residence for PICC maintenance during the treatment interval were set as the observation group. On the basis of the control group, the maintenance method based on the Internet + linkage mode of medical alliance was adopted. The PICC self-management ability, catheter-carrying satisfaction, PICC complication, average cost and average time spent on PICC maintenance during treatment were compared between the two groups.Results:There were no significant differences in the scores of daily life with catheters, exercise with catheters, catheter abnormality handling, compliance with catheter maintenance and confidence in catheter management between the two groups ( P>0.05) . There was no significant difference in the scores of Catheter Satisfaction Survey in the two groups of patients ( P>0.05) .There was also no significant difference in the incidence of PICC complications between the two groups ( P>0.05) . The registration fee, maintenance fee, and transportation fee for PICC maintenance in the observation group were lower than those in the control group, and the round-trip time and visit time were shorter than those in the control group, and the differences were statistically significant ( P<0.05) . Conclusions:The Internet + linkage model based on the medical alliance can ensure the quality of PICC maintenance for patients with malignant tumors undergoing PICC chemotherapy and discharged with catheters, and improve their PICC self-management ability, which has good economic and time benefits.

As self-subunit swapping chaperones or metallochaperones, the activators assist nitrile hydratases to take up metal ions and they are essential for active expression of nitrile hydratases. Compared with nitrile hydratases, the activators have a low sequence identity. Study of the activation characteristics and the relationships between structures and functions of the activators is of great significance for understanding the maturation mechanism of nitrile hydratase. We co-expressed low-molecular-mass nitrile hydratase (L-NHase) from Rhodococcus rhodochrous J1 with four heterologous activators respectively and determined their activation abilities. Then we made sequence analysis and structure modelling, and studied the functions of the important domains of the activators. Results showed that all four heterologous activators could activate L-NHase, however, the specific activities of L-NHases were different after activation. L-NHase showed the highest specific activity after being activated by activator A, which was 97.79% of that of the original enzyme, but the specific activity of L-NHase after being activated by activator G was only 23.94% of that of the original enzyme. Activator E and activator G had conserved domains (TIGR03889), and deletion of their partial sequences resulted in a substantial loss of activation abilities for both activators. Replacing the N-terminal sequence of activator G with the N-terminal sequence of activator E, and adding the C-terminal sequence of activator E to the C-terminus of activator G could increase the specific activity of L-NHase by 178.40%. The activation by nitrile hydratase activators was universal and specific, and the conserved domains of activators were critical for activation, while the N-terminal domain and C-terminal domain also had important effects on activation.

The effect of methanol addition on the heterologous expression of isoprenyl transferase NovQ was studied in Pichia pastoris Gpn12, with menadione and isopentenol as precursors to catalyze vitamin K2 (MK-3) synthesis. The expression of NovQ increased by 36% when 2% methanol was added every 24 h. The influence of initial pH, temperature, methanol addition, precursors (menadione, isopentenol) addition, catalytic time and cetyltrimethyl-ammonium bromide (CTAB) addition were explored in the P. pastoris whole-cell catalytic synthesis process of MK-3 in shaking flask. Three significant factors were then studied by response surface method. The optimal catalytic conditions obtained were as follows: catalytic temperature 31.56 ℃, menadione 295.54 mg/L, catalytic time 15.87 h. Consistent with the response surface prediction results, the optimized yield of MK-3 reached 98.47 mg/L in shaking flask, 35% higher than that of the control group. On this basis, the production in a 30-L fermenter reached 189.67 mg/L when the cell catalyst of 220 g/L (dry weight) was used to catalyze the synthesis for 24 h. This method laid the foundation for the large-scale production of MK-3 by P. pastoris Gpn12.

Enzymatic synthesis is an important way to produce β-alanine, but the biological method is expensive generally because of the high price of substrate. In this paper, a two-step enzymatic cascade system was developed, combining L-aspartase from Escherichia coli DH5α and L-aspartate α-decarboxylase from Corynebacterium glutamicum. This system catalyzes Fumarate and ammonia to β-alanine. The optimal ratio of AspA and PanD was 1:80 (W/W), and the concentration of AspA was 10 μg/mL, at 37 ℃ and pH 7.0. When the concentration of Fumarate was 100 mmol/L, the reaction reached its equilibrium after 8 h, and the yield of β-alanine was 90 mmol/L (7 g/L). The yield of β-alanine can reach 126 mmol/L (9.8 g/L) when the concentration of Fumarate increased to 200 mmol/L. Extending reaction time, the conversion rate did not change obviously. Using this two-step enzymatic cascade system, β-alanine from cheaper substrate Fumarate can be obtained.

Objective To investigate clinical value of high sensitive-cardiac troponin T(hs-cTnT) combined with creatine kinase isoenzyme MB(CK-MB) in the diagnosis of children with myocarditis.Methods From Nov.2014 to Nov.2015,a total of 102 cases of myocarditis,suspected with myocardial damage and without myocardial damage(pneumonia and capillary bronchitis),and 50 healthy children were enrolled.Plasma levels of hs-cTnT and CK-MB were detected and compared.Results The levels of plasma hs-cTnT and CK-MB in children with myocarditis were significantly higher than those without myocarditis and healthy subjects(P<0.05).Hs-cTnT and CK-MB levels in children with myocarditis,less than one month old,were significantly higher than those with age of 1 month to 3 years old(P<0.05).Conclusion Combined detection of hs-cTnT and CK-MB could be with high sensitive and specificity in diagnosis of children with myocarditis,accurately assess the disease condition and improve the therapeutic effect and prognosis,which might be worthy of clinical application.