OBJECTIVES: To investigate the role of DTX2 in regulating biological behaviors of oxaliplatin-resistant colorectal cancer cells (CRC/OXA cells). METHODS: CCK8 assay was used to determine the inhibition rate of oxaliplatin-treated CRC cells. A CRC/OXA cell line was constructed, in which DTX2 expression level was detected. The cells were transfected with a DTX2-shRNA plasmid or co-transfected with DTX2-shRNA and pcDNA-Notch2, and the changes in cell proliferation, migration and invasion ability were evaluated using plate cloning assay, scratch assay and Transwell invasion assay. The expression levels of Notch2, NICD and epithelial-mesenchymal transition (EMT) proteins of the transfected cells were detected with Western blotting. In a nude mouse model bearing SW620/OXA cell xenografts, the effects of DTX2 knockdown and Notch2 overexpression in the implanted cells on tumor growth and protein expressions were tested. RESULTS: The IC₅₀ of oxaliplatin was 6.00 μmol/L in SW620 cells and 8.00 μmol/L in LoVo cells. CRC/OXA cells showed a significantly increased expression of DTX2. DTX2 knockdown in CRC/OXA cells significantly inhibited cell proliferation, migration and invasion, and these effects were reversed by co-transfection of the cells with pcDNA-Notch2. DTX2 knockdown significantly reduced the expression levels of Notch2, NICD and vimentin proteins and increased E-cadherin expression in CRC/OXA cells, and co-transfection with pcDNA-Notch2 potently attenuated the changes in these proteins. In the tumor-bearing mice, DTX2 overexpression obviously promoted the growth of SW620/OXA cell xenograft, enhanced the protein expressions of Notch2, NICD and vimentin, and lowered the expression of E-cadherin. CONCLUSIONS High expression of DTX2 promotes proliferation, migration, invasion and EMT of CRC/OXA cells through the Notch2 signaling pathway, suggesting the potential of DTX2 as a target to improve the efficacy of oxaliplatin.
Epithelial-Mesenchymal Transition ; Humans ; Cell Proliferation ; Oxaliplatin ; Colorectal Neoplasms/metabolism* ; Animals ; Drug Resistance, Neoplasm ; Receptor, Notch2/metabolism* ; Cell Line, Tumor ; Mice, Nude ; Cell Movement ; Organoplatinum Compounds/pharmacology* ; Neoplasm Invasiveness ; Mice

This study aimed to comprehensively examine the association of gallstones, cholecystectomy, and cancer risk. Multivariable logistic regressions were performed to estimate the observational associations of gallstones and cholecystectomy with cancer risk, using data from a nationwide cohort involving 239 799 participants. General and gender-specific two-sample Mendelian randomization (MR) analysis was further conducted to assess the causalities of the observed associations. Observationally, a history of gallstones without cholecystectomy was associated with a high risk of stomach cancer (adjusted odds ratio (aOR)=2.54, 95% confidence interval (CI) 1.50-4.28), liver and bile duct cancer (aOR=2.46, 95% CI 1.17-5.16), kidney cancer (aOR=2.04, 95% CI 1.05-3.94), and bladder cancer (aOR=2.23, 95% CI 1.01-5.13) in the general population, as well as cervical cancer (aOR=1.69, 95% CI 1.12-2.56) in women. Moreover, cholecystectomy was associated with high odds of stomach cancer (aOR=2.41, 95% CI 1.29-4.49), colorectal cancer (aOR=1.83, 95% CI 1.18-2.85), and cancer of liver and bile duct (aOR=2.58, 95% CI 1.11-6.02). MR analysis only supported the causal effect of gallstones on stomach, liver and bile duct, kidney, and bladder cancer. This study added evidence to the causal effect of gallstones on stomach, liver and bile duct, kidney, and bladder cancer, highlighting the importance of cancer screening in individuals with gallstones.
Humans ; Mendelian Randomization Analysis ; Gallstones/complications* ; Female ; Male ; Cholecystectomy/statistics & numerical data* ; Middle Aged ; Risk Factors ; Aged ; Adult ; Neoplasms/etiology* ; Stomach Neoplasms/epidemiology*

Objective: To analyze the changing trend and distribution characteristics of hepatitis C virus (HCV) infection among blood donors in Hebei, thereby providing data to support strategy and procedure adjustment for blood collection and supply institutions. Methods: Data from 12 blood stations in Hebei Province from 2012 to 2021 were collected. These data were analyzed to determine trends in anti-HCV antibody double reagent reactive rate and to characterize its distribution among different donor categories, genders and birth cohorts. Results: During the period from 2012 to 2021, a total of 7.4576 million samples were tested at 12 blood stations in Hebei Province, with 3.4659 million (46.47%) from first-time donors, and 3.9917 million (53.53%) from repeat donors. The number (of anti-HCV double reagent reactive samples was 7167 (9.61/10 000). The anti-HCV double reagent reactive rate showed a annual downward trend (P<0.05), from 17.40/10 000 at the beginning to 4.95/10 000 at the end of the study period. Additionally, the double reagent reactive rate of repeat blood donors had remained below 1/10 000 since 2017. The double reagent reactive rate of first-time blood donors (19.42/10 000) was higher than in repeat donors (1.09/10 000) (P<0.05), and the double-reagent reactive rate of female first-time blood donors (20.98/10 000) was higher than that of male first-time blood donors (18.49/10 000) (P<0.05). The anti-HCV double reagent reactive rate among first-time donors exhibited two distinct peaks within the pre-1976 and 1989-1994 birth cohorts, with notable gender differences observed in both peak periods. The rate of double reagent reactive in females born before 1976 (52.22/10 000) was higher than that in males (32.28/10 000) (P<0.05), while that of males born in 1989-1994 was higher (25.75/10 000) than that of females (14.28/10 000) (P<0.05). Conclusion: The prevalenc of HCV infection among blood donors in Hebei Province has shown a consistent year-over-year decline over the study period. The majority of infected individuals are found among the first-time blood donors born before 1995. These trends and characteristics provide valuable insights for developing pre-blood collection screening strategies, analyzing nucleic acid test data in blood screening, adjusting blood screening procedures, and provide evidence for targeted screening of high-risk populations as part of public health initiatives to eliminate hepatitis C.

Objective To investigate the application value of quantitative parameters MRFDGmax and SUVmax in the stages of hepatitis,liver fibrosis and cirrhosis in rats by whole-body dynamic 18 F-FDG PET/CT Patlak imaging.Methods Twenty-four SD rats were randomly divided into four groups of six rats each,which were the normal group,hepatitis group,liver fibrosis group and cirrhosis group.According to the experimental grouping,rats in each group were induced by the CC14 oil solution complex method.Whole-body dynamic 18 F-FDG PET/CT patlak imaging was performed on each group of rats separately at the completion of induction.After the imaging was com-pleted,the MRFDGmax,SUVmax and CT values of the livers of each group were analyzed;subsequently,the serum of rats in each group was extracted for the detection of liver function indexes(AST,ALT and ALP),and HE staining was performed on the livers of rats in the normal,hepatitis and cirrhosis groups,and Masson staining was performed on those in the liver fibrosis group;the α-SMA expression in the liver tissues of each group was analyzed by immu-nohistochemical method.The data were analyzed by one-way ANOVA,two independent samples t-test and Pearson correlation analysis.Results MRFDGmax,SUVmax values were statistically significant differences among normal,hep-atitis,liver fibrosis and cirrhosis groups(F=84.54,38.35,P＜0.001).The difference in CT values between liver fibrosis and cirrhosis groups was not statistically significant(t=-0.407,P=0.693),and the difference was statistically significant when compared between the rest of the groups(F=112.25,P＜0.001).Compared with the normal group,AST,ALT and ALP of the experimental group showed a staged increase,and the differences were statistically significant(F=93.32,64.63,145.03,P＜0.001).HE staining showed that hepatocytes of the normal group were neatly arranged and structurally intact;a large number of inflammatory cells infiltrated the hepa-titis group with steatosis;pseudo lobe formation was observed in the cirrhosis group.Masson staining of the liver fi-brosis group showed collagen fiber proliferation and thickening of the peritoneum.Immunohistochemistry test results showed that α-SMA expression increased in hepatitis group,liver fibrosis group and cirrhosis group,with a staged increase,and the difference was statistically significant(F=80.57,P＜0.001).Correlation analysis showed a positive correlation between SUVmax and MRFDGmax(r=0.967,P＜0.01).α-SMA was positively correlated with AST,ALT and ALP in the hepatitis,liver fibrosis and cirrhosis groups,respectively(r=0.924,0.756,0.934,P＜0.01).Conclusion Whole-body dynamic 18F-FDG PET/CT Patlak imaging has application value in monitoring hepatitis,liver fibrosis and cirrhosis stages through quantitative parameters MRFDGmax and SUVmax changes.

Objective:To investigate the current situation of the use of transjugular intrahepatic portosystemic shunt (TIPS) for portal hypertension, which should aid the development of TIPS in China.Methods:The China Portal Hypertension Alliance (CHESS) initiated this study that comprehensively investigated the basic situation of TIPS for portal hypertension in China through network research. The survey included the following: the number of surgical cases, main indications, the development of Early-TIPS, TIPS for portal vein cavernous transformation, collateral circulation embolization, intraoperative portal pressure gradient measurement, commonly used stent types, conventional anticoagulation and time, postoperative follow-up, obstacles, and the application of domestic instruments.Results:According to the survey, a total of 13 527 TIPS operations were carried out in 545 hospitals participating in the survey in 2021, and 94.1% of the hospital had the habit of routine follow-up after TIPS. Most hospitals believed that the main indications of TIPS were the control of acute bleeding (42.6%) and the prevention of rebleeding (40.7%). 48.1% of the teams carried out early or priority TIPS, 53.0% of the teams carried out TIPS for the cavernous transformation of the portal vein, and 81.0% chose routine embolization of collateral circulation during operation. Most of them used coils and biological glue as embolic materials, and 78.5% of the team routinely performed intraoperative portal pressure gradient measurements. In selecting TIPS stents, 57.1% of the hospitals woulel choose Viator-specific stents, 57.2% woulel choose conventional anticoagulation after TIPS, and the duration of anticoagulation was between 3-6 months (55.4%). The limitation of TIPS surgery was mainly due to cost (72.3%) and insufficient understanding of doctors in related departments (77.4%). Most teams accepted the domestic instruments used in TIPS (92.7%).Conclusions:This survey shows that TIPS treatment is an essential part of treating portal hypertension in China. The total number of TIPS cases is far from that of patients with portal hypertension. In the future, it is still necessary to popularize TIPS technology and further standardize surgical indications, routine operations, and instrument application.

OBJECTIVE To study the regulation effects and mechanism of liquiritin （LIQ） on immune function in gastric cancer-bearing mice based on the Janus kinase 2 （JAK2）/signal transducer and activator of transcription 3 （STAT3） pathway. METHODS Gastric cancer cells MFC were injected subcutaneously to establish gastric cancer-bearing model of mice. The model mice were divided into model group， LIQ low-dose group （LIQ-L group， 20 mg/kg）， LIQ high-dose group （LIQ-H group， 40 mg/kg）， and high-dose LIQ+JAK2 activator coumermycin A1 group （LIQ-H+coumermycin A1 group， 40 mg/kg LIQ+1 mg/kg coumermycin A1）， with 12 mice in each group. Another 12 mice without modeling were set as normal group. Mice in each group were given the corresponding drug or normal saline by intragastric administration/intraperitoneal injection， once a day， for consecutive 14 days. After the last administration， the volume and mass of gastric cancer tumor and organ index were measured. The percentages of CD4+ and CD8+T lymphocytes were detected in peripheral blood. The histopathological morphology of gastric cancer tumor tissues was observed， and the expression levels of JAK2/STAT3 signaling pathway-related proteins and interleukin-6 （IL-6） protein in gastric cancer tumor tissues were detected. RESULTS Compared with the normal group， the thymus index， spleen index， and the percentage of CD8 T lymphocyte in the peripheral blood of mice were obviouslyincreased in model group （P＜0.05）， while the percentage of CD4+T lymphocyte in the peripheral blood were decreased （P＜0.05）. Compared with model group， the above indexes in LIQ-L group and LIQ-H group were significantly reversed （P＜0.05）， while the volume and mass of gastric cancer tumor， the phosphorylation levels of JAK2 and STAT3 protein and the expression level of IL-6 protein were significantly decreased in tumor tissue （P＜0.05）， and the effect of LIQ was in a dose-dependent manner （P＜0.05）； the tumor cells showed varying degrees of loose arrangement， vacuolization， and uneven distribution. JAK2 activator coumermycin A1 weakened the improvement effect of LIQ on the immune function of gastric cancer-bearing mice and its inhibitory effect on gastric cancer tumors （P＜0.05）. CONCLUSIONS LIQ can improve the immune function of gastric cancer-bearing mice by inhibiting the activation of JAK2/STAT3 signaling pathway， thus playing an anti-tumor role.

Objective To investigate the initial dose and safety of intravenous infusion of sodium (s)-2-(dithiocarboxylato((2R,3R,4R,5R,6R)-2,3,4,5,6-pentahydroxyhexyl) amino)-4-(methylthio) butanoate (GMDTC) for the displacement of cadmium. Methodsi) Efficacy test. The New Zealand male rabbits were randomly divided into model group, calcium disodium edetate (EDTA) group and GMDTC low-, medium- and high-dose groups after cadmium poisoning using 2.5 cadmium chloride dihydrate. Rabbits in EDTA group were intravenously injected with EDTA dipotassium at a dose of 93.5 mg/kg body weight, rabbits in the three doses groups were intravenously injected of GMDTC at doses of 12.0, 36.0, and 108.0 mg/kg body weight, respectively. The rabbits in the control group (separate set) and model group were intravenously injected with equal volumes of 0.9% sodium chloride solution, administered for five consecutive days per week for 1, 2, and 4 weeks. ii) Toxicity test. Specific pathogen free SD rats were randomly divided into solvent control group and low-, medium- and high-dose groups. In the acute toxicity test, the rats in the three-dose groups were intravenously injected of GMDTC at doses of 200.0, 800.0 and 3 000.0 mg/kg body weight, respectively. In the long-term toxicity test, the rats in the three-dose groups were intravenously injected GMDTC at doses of 100.0, 500.0 and 2 000.0 mg/kg body weight, respectively, once a day for four consecutive weeks, with a recovery period of four weeks. The rats in the solvent control group were given an equal volume 0.9% sodium chloride solution intravenously at the same time. The maximum tolerated dose (MTD) and no observable adverse effect level (NOAEL) were detected. Resultsi) In the one week treatment experiment, the 24 hours urinary cadmium levels of rabbits in the three doses groups were higher than those in the model group at the same time point (all P<0.05). In the two weeks treatment experiment, the 24 hours urinary cadmium levels of rabbits in medium-dose and high-dose groups at the three time points were higher than those in the model group at the same time point (all P<0.05). In the four weeks treatment experiment, the 24 hours urinary cadmium level on the 19th day of rabbits in the low-dose group was higher than that in the model group at the same time point (P<0.05), and the 24 hours urinary cadmium levels of rabbits in medium- and high-dose groups at the five time points were higher than those in the model group at the same time point (all P<0.05), except for the rabbits of fifth day of the medium-dose group. The kidney cadmium levels of rabbits in the low-dose group after four week of treatment and in the medium- and high-dose groups after one, two, and four weeks of treatment decreased compared with the model group (all P<0.05). No obvious adverse effects were observed during the treatment. ii) The MTD of GMDTC in rats administered intravenously in a single dose was 3 000.0 mg/kg body weight. During the period of intravenous infuseion with GMDTC for four consecutive weeks, the blood drug level reached the peak at the end of the first and last administrations (eight min), and no clinical adverse reactions were observed during this period of time, nor was there any apparent accumulation. The NOAEL for intravenous infusion of GMDTC for four consecutive weeks in rats was 500.0 mg/kg body weight. Conclusion The initial dose of the GMDTC injection in the cadmium poisoning rabbit was 36.0 mg/kg body weight, and the recommended initial dose for human is 480.0 mg/person. Intravenous infusion of GMDTC is characterized by rapid absorption, rapid elimination, and no accumulation.

【Objective】 To develop a clinical prediction model based on ⁶⁸Ga-prostate-specific membrane antigen-11 (⁶⁸Ga-PSMA-11), positron emission tomography/computed tomography (PET/CT) and multiparametric magnetic resonance imaging (mpMRI) parameters to stratify prostate cancer patients undergoing targeted biopsy, so as to avoid unnecessary systematic biopsy. 【Methods】 A total of 96 clinically significant prostate cancer (csPCa) patients who underwent ⁶⁸Ga-PSMA-11 PET/CT and mpMRI prior to prostate targeted biopsy with systematic biopsy during Jan.2020 and Feb.2023 in Nanjing Drum Tower Hospital were retrospectively analyzed.By univariate and multivariate logistic regression analyses, maximum standard uptake value (SUVmax) in ⁶⁸Ga-PSMA-11 PET/CT and minimum apparent diffusion coefficien (ADCmin) in mpMRI, as well as clinical parameters were evaluated to identify the independent predictors correlative with the effective diagnosis of targeted biopsy, and a clinical prediction model was constructed. 【Results】 Multivariate logistic regression analysis showed that SUVmax (OR=0.878, 95%CI: 0.804-0.959, P=0.004) and ADCmin (OR=1.005, 95%CI:1.001-1.010, P=0.027) were independent predictors of the effective diagnosis of targeted biopsy alone.The sensitivity, specificity, accuracy and area under the receiver operator characteristic curve (AUC) of the model were 0.80, 0.80, 0.83 and 0.84, respectively. 【Conclusion】 The clinical prediction model based on ⁶⁸Ga-PSMA-11 PET/CT and mpMRI parameters is helpful to improve the effective diagnosis of targeted biopsy alone, and has practical value to stratify patients with csPCa so as to safely avoid systematic biopsy and effectively balance the benefits and risks.

Objective To monitor and evaluate the synergistic antitumor effects of programmed death-1(PD-1)checkpoint inhibitor combined with radiation therapy through whole-body dynamic 18 F-Fluorodeoxy glucose positron emission computed tomography(18F-FDG PET/CT)and Patlak multi-parametric analysis.Methods B16F10 mel-anoma dual-tumor mouse model was established and randomly divided into control,PD-1 monoclonal antibody,ra-diation-only,and combination groups(n=6).Whole-body 18F-FDG PET/CT imaging was performed before and 24 hours post-treatment.The changes of maximum standardized uptake value(SUVmax)and metabolic rate of FDG(MRFDG)changes were analyzed and compared.Mice were then euthanized,tumors excised and underwent histo-pathology with HE,CD8,Ki-67 staining to assess immune infiltration and proliferation.Distal tumor volumes were monitored during treatment.Results At 24 hours post-treatment,in the primary tumors,SUVmax and MRFDG values increased compared to pre-treatment in the control group(P＜0.000 1),while they decreased in the combination treatment group(P＜0.000 1),with statistically significant differences.In the distal tumors,SUVmax and MRFDG values increased compared to pre-treatment in the control group,PD-1 monoclonal antibody group,and radiothera-py-alone group.The SUVmax differences were statistically significant in the control group before and after treatment(P＜0.000 1).MRFDG values in the distal tumors showed statistically significant differences in all three groups(P＜0.01 or P＜0.000 1).In the combination treatment group,SUVmax and MRFDG values in the distal tumors de-creased significantly compared to pre-treatment(P＜0.000 1).Post-treatment comparison of SUVmax and MRFDG values in the distal tumors showed that statistically significant differences in SUVmax and MRFDG values were observed among all groups except between the radiotherapy-alone and PD-1 monoclonal antibody groups(all P＜0.05).Im-munohistochemistry results showed that the mean absorbance value of CD8 T lymphocytes in the distal tumor was significantly higher than that in the other three groups(P＜0.001);the mean absorbance value of Ki-67 immuno-histochemistry in the distal tumor proliferation index was significantly lower than that in the other three groups(P＜0.001).Conclusion The synergistic effects of combined treatment reduced distal tumor growth.Whole-body 18F-FDG PET/CT Patlak multi-parametric imaging can monitor the synergistic effects of PD-1 antibody and radiotherapy in B16F10 melanoma,providing reliable imaging parameters for optimizing combinatorial therapies.

Background and Aims:Preoperative sarcopenia is a syndrome characterized by reduced skeletal muscle mass and strength,and it is associated with various adverse postoperative outcomes.Gastric cancer patients may experience transient or persistent postoperative cognitive dysfunction(POCD),which significantly impacts their quality of life and prognosis.However,it remains unclear whether this complication is linked to sarcopenia.Therefore,this study was conducted to investigate further the impact of preoperative sarcopenia on postoperative complications and long-term outcomes in patients undergoing radical gastric cancer surgery,with a particular focus on the relationship between sarcopenia and POCD,in order to provide insights for preoperative assessment and postoperative management of gastric cancer patients. Methods:The clinical data of gastric cancer patients who underwent radical surgery in the Third Department of Surgery at the Fourth Hospital of Hebei Medical University between January 2014 and January 2015 were retrospectively collected.Patients were divided into the sarcopenia and non-sarcopenia groups based on preoperative L3 skeletal muscle index,handgrip strength,and gait speed measurements.The clinicopathologic characteristics of sarcopenic patients,as well as the impact of sarcopenia on short-term clinical outcomes and long-term prognosis,were analyzed.Additionally,factors influencing the development of POCD were determined. Results:A total of 320 gastric cancer patients were included,of whom 59(18.44％)were diagnosed with sarcopenia.Compared with the non-sarcopenia group,sarcopenic patients had significantly lower bady mass index,serum total protein,serum albumin,and hemoglobin levels,with a higher proportion of patients aged ≥60 years,NRS 2002 score ≥3,comorbid pulmonary disease,and those undergoing open surgery(all P＜0.05).After balancing the baseline characteristics of the two groups using propensity score matching(PSM),each group included 59 patients.The analysis revealed that the overall incidence of postoperative complications was higher in the sarcopenia group than in the non-sarcopenia group(54.24％vs.32.20％,P=0.016).The sarcopenia group also had a significantly higher incidence of Clavien-Dindo grade Ⅱ-Ⅳ complications and postoperative infectious complications(27.12％vs.5.08％,P=0.001;33.90％vs.15.25％,P=0.019).The average hospital stay was significantly longer for sarcopenic patients(12.54±4.7 d vs.7.68±3.8 d,P=0.005).Additionally,the 5-year overall survival(OS)and disease-free survival(DFS)rates were lower in the sarcopenia group compared to the non-sarcopenia group(both P＜0.05).Cox multivariate analysis showed that sarcopenia,tumor pT stage,and tumor pN stage were independent risk factors for 5-year OS and DFS.At the same time,adjuvant chemotherapy was a protective factor for prognosis(all P＜0.05).Among the 118 patients after PSM,34(28.81％)were diagnosed with POCD.Logistic multivariate regression analysis indicated that preoperative sarcopenia,the number of preoperative comorbidities,and anesthesia duration of ≥2 h were independent risk factors for POCD,while intraoperative use of dexmedetomidine was a protective factor(all P＜0.05). Conclusion:Preoperative sarcopenia is closely associated with unfavorable postoperative outcomes and the development of POCD in patients undergoing radical gastric cancer surgery.Clinicians should emphasize the detection of sarcopenia during preoperative evaluation and implement proactive interventions and postoperative management strategies to improve clinical outcomes and long-term survival rates.