Objective To explore the expression of long non-coding ribonucleic acid(lncRNA)metastasis-associated lung adenocarcinoma transcript 1(MALAT1)and nuclear paraspeckle assembly transcript 1(NEAT1)in the hippocampus and HT22 cells of hypoxia pre-acclimated(HPC)mice and their relationship with neuroprotection.Methods(1)Thirty-six male Institute of Cancer Research(ICR)mice were randomly divided into three groups according to the random number table method of complete randomization:the control group,the hypoxia group and the hypoxia preconditioning group,with 12mice in each group.Mice in the control group were not exposed to hypoxia,mice in the hypoxia group were exposed to hypoxia once,and mice in the hypoxia preconditioning group were exposed to hypoxia four times.Immediately after the end of hypoxia treatment,all mice were decapitated and killed and hippocampal tissues were isolated and preserved in groups.(2)HT22 cells were cultured in medium containing 10％foetal bovine serum and 100 U/ml penicillin-streptomycin.When cell confluence was greater than 90％,they were transferred to 24-well plates for culture and then processed in 2 batches.6 pmol disordered small interfering RNA(siRNA),MALAT1 siRNA(siMALAT1),NEAT1 siRNA(siNEAT1),siMALAT1+siNEAT1 were transfected into the negative control group,siMALAT1 group,siNEAT1 group,and siMALAT1+siNEAT1 group of the first batch of HT22 cells one by one by transfection reagent,and the blank group did not have any treatment;then they were cultured under normal conditions(5％CO2 and 95％air)for 48 h.In the second batch of HT22 cells,6 pmol of disordered siRNA,disordered siRNA,siMALAT1,siMALAT1,siNEAT1 and siNEAT1 were transfected one by one correspondingly to the negative control group and the negative control+oxygen-glucose deprived/reoxygen(OGD/R)group,siMALAT1 group,siMALAT1+OGD/R,siNEAT1 group,siNEAT1+OGD/R group.48 h after transfection,HT22 cells of negative control group,siMALAT1 group and siNEAT1 group were cultured under normal conditions(5％CO2 and 95％air),and the cells of negative control+OGD/R group,siMALAT1+OGD/R group and siNEAT1+OGD/R group were treated with OGD/R.That is,under low oxygen conditions(1％O2+5％CO2+94％N2)exposure for 8 h,and then culture under normal conditions for 16 h.(3)The real-time fluorescence quantitative polymerase chain reaction(PCR)and Western blot was used to determine the expression of MALAT1,NEAT1,N-methyl-D-aspartate receptor subunit 2B(NR2B)messenger RNA(mRNA)and NR2B protein in the hippocampus of mice,the relative expression levels of NR2B mRNA and NR2B protein after transfection of HT22 cells in each group,and the relative expression levels of haemoglobin breakdown products and activated cysteine protease protein 3 after transfection and OGD/R of HT22 cells in each group.The survival rate of HT22 cells in each group was calculated.Results(1)The differences in relative expression of MALAT1(F=43.92),NEAT1(F=506.4),NR2B mRNA(F=50.64)and NR2B protein(F=41.24)in the hippocampus of mice in the three groups were statistically significant(all P＜0.05).The relative expression of MALAT1([1.68±0.06]vs.[1.00±0.08]),NR2B mRNA([1.26±0.06]vs.[1.00±0.01]),and NR2B protein([1.47±0.05]vs.[1.00±0.01])was increased in the hypoxia group as compared to the control group(all P＜0.05),whereas the relative expression of NEAT1([1.02±0.10]vs.[1.00±0.03])were not statistically significant(P＞0.05),and the relative expression of MALAT1([1.12±0.13]vs.[1.00±0.08])and NEAT1([2.88±0.10]vs.[1.00±0.03])were increased in hypoxic preconditioned group.Compared with hypoxia group,the relative expression of NR2B mRNA([0.54±0.07]vs.[1.26±0.06])and NR2B protein([1.17±0.07]vs.[1.47±0.05])were decreased(both P＜0.05).(2)The differences in the relative expression of NR2B mRNA(F=36.92)and NR2B protein(F=56.98)after transfection of HT22 cells in the five groups were statistically significant(both P＜0.05).Compared with the negative control group,siMALAT1 group(NR2B mRNA:[2.04±0.08]vs.[0.94±0.04],NR2B protein:[1.72±0.13]vs.[0.93±0.02]),siNEAT1 group(NR2B mRNA:[2.15±0.13]vs.[0.94±0.04],NR2B protein:[1.87±0.46]vs.[0.93±0.02]),siMALAT1+siNEAT1 group(NR2BmRNA:[2.09±0.16]vs.[0.94±0.04],NR2B protein:[2.07±0.30]vs.[0.93±0.02])showed the relative NR2B mRNA and NR2B protein expression were increased(all P＜0.05).(3)Differences in relative expression of haematopoietin breakdown product(145/150 kDa)protein(F=12.43),haematopoietin breakdown product(120 kDa)protein(F=7.15),and activated cysteamine protease protein 3 protein(F=6.61)were statistically significant in the 6 groups of HT22 cells transfected and treated with OGD/R(all P＜0.05).Compared with the siMALAT1 group,the siMALAT1+OGD/R group had 145/150kDa([1.42±0.48]vs.[0.85±0.34]),120 kDa([1.33±0.37]vs.[0.52±0.19])haematopoietin catabolism products and activated cysteamine protease protein 3([2.43±0.35]vs.[1.15±0.24])relative expression increased(all P＜0.05);compared with the negative control+OGD/R group,the siMALAT1+OGD/R group showed an increase in 145/150kDa([1.42±0.48]vs.[1.23±0.17]),120 kDa([1.33±0.37]vs.[0.80±0.21])relative expression of haematopoietin breakdown products and activated cysteamine protease protein 3([2.43±0.35]vs.[1.46±0.39])increased(all P＜0.05);compared with the siNEAT1 group,the siNEAT1+OGD/R group had a higher expression of 145/150 kDa([1.28±0.44]vs.[0.87±0.32]),120 kDa([0.81±0.36]vs.[0.63±0.16])relative expression of haematopoietic proteolytic products and activated cysteamine protease protein 3([1.51±0.45]vs.[1.01±0.27])increased(all P＜0.05).(4)The difference in HT22 cell survival rate among the 6 groups was statistically significant(F=5.54,P＜0.05).Compared with the negative control group,HT22 cell survival was decreased in the siMALAT1,siNEAT1,siMALAT1+OGD/R and siNEAT1+OGD/R groups([0.65±0.40],[0.76±0.35],[0.24±0.17],[0.23±0.16]vs.[0.84±0.04],all P＜0.05);cell viability was reduced in the siMALAT1+OGD/R group compared with the siMALAT1 group([0.24±0.17]vs.[0.65±0.40],P＜0.05);and cell viability was reduced in the siNEAT1+OGD/R group compared with the siNEAT1 group([0.23±0.16]vs.[0.76±0.35],P＜0.05).Conclusion HPC increased the expression of MALAT1 and NEAT1 in the hippocampus of mice,and MALAT1 and NEAT1 may participate in the neuroprotective effect of mice after ischemia and hypoxia by affecting the expression of NR2B.

Objective:To investigate the causal relationship between intestinal flora and benign biliary diseases by genome-wide Mendelian randomization.Methods:This is a retrospective observational study. The data from the genome-wide association study of the gut microbiota from 18 340 samples from the MiBioGen consortium were selected as the exposure group,and the data from the genome-wide association study of biliary tract diseases were obtained from the FinnGen consortium R8 as the outcome group. There were 1 491 cases of primary sclerosing cholangitis,32 894 cases of cholelithiasis,3 770 cases of acalculous cholecystitis,and 34 461 cases of cholecystitis. Single nucleotide polymorphisms were screened as instrumental variables,and the Mendelian randomization method was used to infer the causal relationship between exposures and outcomes. The inverse variance weighting method (IVW) was used as the main basis, supplemented by heterogeneity,pleiotropy and sensitivity tests.Results:Coprococcus 2 was associated with a reduced risk of cholelithiasis (IVW OR=0.88,95% CI:0.80 to 0.97, P=0.012) and cholecystitis (IVW OR=0.88,95% CI:0.80 to 0.97, P=0.011). Coprococcus 3 was associated with cholelithiasis (IVW OR=1.15,95% CI:1.02 to 1.30, P=0.019) and acalculous cholecystitis(IVW OR=1.48, 95% CI: 1.08 to 2.04, P=0.016) and cholecystitis (IVW OR=1.17, 95% CI: 1.02 to 1.33, P=0.020). Peptococcus was associated with an increased risk of cholelithiasis (IVW OR=1.08, 95% CI:1.02 to 1.13, P=0.005) and cholecystitis (IVW CI=1.07, 95% CI:1.02 to 1.13, P=0.010). Clostridiumsensustricto 1 was associated with an increased risk of cholelithiasis (IVW OR=1.16,95% CI:1.02 to 1.31, P=0.020) and cholecystitis (IVW OR=1.16, 95% CI:1.03 to 1.30, P=0.015). Eubacterium hallii was associated with an increased risk of primary sclerosing cholangitis (IVW OR=1.43, 95% CI: 1.03 to 1.99, P=0.033). Eubacterium ruminantium (IVW OR=0.87, 95% CI: 0.76 to 1.00, P=0.043) and Methanobrevibacter (IVW OR=0.81, 95% CI: 0.68 to 0.98, P=0.027) were associated with a reduced risk of acalculous cholecystitis. Conclusions:Eight intestinal bacterial genera maybe play pathogenic roles in benign biliary diseases. Eubacterium hallii can increase the risk of primary sclerosing cholangitis. Peptococcus and Clostridiumsensustricto 1 can increase the risk of cholelithiasis and generalized cholecystitis. Coprococcus 3 have multiple correlations with biliary stones and inflammation.

Objective:To investigate the causal relationship between intestinal flora and benign biliary diseases by genome-wide Mendelian randomization.Methods:This is a retrospective observational study. The data from the genome-wide association study of the gut microbiota from 18 340 samples from the MiBioGen consortium were selected as the exposure group,and the data from the genome-wide association study of biliary tract diseases were obtained from the FinnGen consortium R8 as the outcome group. There were 1 491 cases of primary sclerosing cholangitis,32 894 cases of cholelithiasis,3 770 cases of acalculous cholecystitis,and 34 461 cases of cholecystitis. Single nucleotide polymorphisms were screened as instrumental variables,and the Mendelian randomization method was used to infer the causal relationship between exposures and outcomes. The inverse variance weighting method (IVW) was used as the main basis, supplemented by heterogeneity,pleiotropy and sensitivity tests.Results:Coprococcus 2 was associated with a reduced risk of cholelithiasis (IVW OR=0.88,95% CI:0.80 to 0.97, P=0.012) and cholecystitis (IVW OR=0.88,95% CI:0.80 to 0.97, P=0.011). Coprococcus 3 was associated with cholelithiasis (IVW OR=1.15,95% CI:1.02 to 1.30, P=0.019) and acalculous cholecystitis(IVW OR=1.48, 95% CI: 1.08 to 2.04, P=0.016) and cholecystitis (IVW OR=1.17, 95% CI: 1.02 to 1.33, P=0.020). Peptococcus was associated with an increased risk of cholelithiasis (IVW OR=1.08, 95% CI:1.02 to 1.13, P=0.005) and cholecystitis (IVW CI=1.07, 95% CI:1.02 to 1.13, P=0.010). Clostridiumsensustricto 1 was associated with an increased risk of cholelithiasis (IVW OR=1.16,95% CI:1.02 to 1.31, P=0.020) and cholecystitis (IVW OR=1.16, 95% CI:1.03 to 1.30, P=0.015). Eubacterium hallii was associated with an increased risk of primary sclerosing cholangitis (IVW OR=1.43, 95% CI: 1.03 to 1.99, P=0.033). Eubacterium ruminantium (IVW OR=0.87, 95% CI: 0.76 to 1.00, P=0.043) and Methanobrevibacter (IVW OR=0.81, 95% CI: 0.68 to 0.98, P=0.027) were associated with a reduced risk of acalculous cholecystitis. Conclusions:Eight intestinal bacterial genera maybe play pathogenic roles in benign biliary diseases. Eubacterium hallii can increase the risk of primary sclerosing cholangitis. Peptococcus and Clostridiumsensustricto 1 can increase the risk of cholelithiasis and generalized cholecystitis. Coprococcus 3 have multiple correlations with biliary stones and inflammation.

Objective:To investigate the prognostic factors for liver transplantation for hepatocellular carcinoma beyond UCSF criteria but without macrovascular invasion.Methods:A retrospective analysis was performed for the clinical data of the hepatocellular carcinoma patients without macrovascular invasion beyond UCSF criteria who underwent liver transplantation at our center from Jan 2018 to Jun 2023. The receiver operating characteristic curve analysis was performed to assess the predictive power of potential prognosis factors.Results:With this criteria, the 1-, 3-year overall survival rates were 94.1% and 75.0%, respectively, and the 1-, 3-year tumor free survival rates were 82.4% and 38.1%, respectively. The maximum tumor size, number of tumors, AFP, PIVKA-Ⅱ before transplantation, and whether undergo pretransplant down-stage therapy were significant prognostic factors ( P<0.05). Combining the above prognostic factors to construct the receiver operating characteristic curve yielded an area under the curve of 0.967, with a sensitivity and specificity of 0.932, 0.952, respectively. Further, the differentiation, MVI and Ki-67 were significant prognostic factors ( P<0.05). Combining pathological factors to construct the receiver operating characteristic curve yielded an area under the curve of 0.927, with a sensitivity and specificity of 0.769, 1, respectively. Conclusion:The maximum tumor diameter, number of tumors, AFP, PIVKA-Ⅱ before transplantation, and pretransplant down-stage therapy and tumor differentiation, MVI and Ki-67 are all prognostic factors of liver transplantation for hepatocellular carcinoma without macrovascular invasion beyond UCSF criteria.

Objective    To compare the perioperative outcomes between robot-assisted complex segmentectomy and simple segmentectomy for stage ⅠA non-small cell lung cancer (NSCLC). Methods    The clinical data of 285 patients with NSCLC undergoing robot-assisted thoracic surgery (RATS) in our hospital from January 2015 to August 2021 were retrospectively analyzed. There were 105 males and 180 females aged 23-83 years. The patients were divided into a complex segmentectomy group (n=170) and a simple segmentectomy group (n=115) according to tumor location and surgical method. The clinical pathological baseline characteristics and perioperative outcomes between the two groups were compared, including operative time, blood loss volume, dissected lymph nodes, conversion rate, postoperative duration of drainage, postoperative hospital stay, the incidence of persistent air leakage and postoperative 30 d mortality. Results    There was no statistical difference in baseline data between the two groups (P>0.05). No postoperative 30 d death was observed. One patient in the complex segmentectomy group was transferred to thoracotomy. No statistical difference was observed between the two groups in the operative time (97.36±38.16 min vs. 94.65±31.67 min, P=0.515),  postoperative duration of drainage (3.69±1.85 d vs. 3.60±1.90 d, P=0.679), postoperative hospital stay (4.07±1.85 d vs. 4.05±1.97 d, P=0.957), dissected lymph nodes (5.15±3.53 vs. 5.13±2.93, P=0.952), incidence of blood loss volume<100 mL (98.2% vs. 99.1%, P=0.650), and incidence of postoperative persistent air leakage (6.5% vs. 5.2%, P=0.661). Conclusion    The safety and effectiveness of robot-assisted complex segmentectomy and simple segmentectomy are satisfactory in the treatment of stage ⅠA NSCLC. The perioperative results of RATS complex segmentectomy and simple segmentectomy are similar.

Objective    To investigate the effectiveness and safety of robotic lobectomy in clinical N0 lung malignant tumor≥3 cm. Methods    We retrospectively analyzed the clinical data of 182 patients with lung malignant tumor≥3 cm receiving robotic or thoracoscopic lobectomy at Shanghai Chest Hospital in 2019. The patients were divided into a robotic surgery group (RATS group) and a thoracoscopic surgery group (VATS group). There were 39 males and 38 females with an average age of 60.55±8.59 years in the RATS group, and 51 males and 54 females with an average age of 61.58±9.30 years in the VATS group. A propensity score matching analysis was applied to compare the operative data between the two groups. Results    A total of 57 patients were included in each group after the propensity score matching analysis. Patients in the RATS group had more groups of N1 lymph node dissected (2.53±0.83 groups vs. 2.07±0.88 groups, P=0.005) in comparison with the VATS group. No statistical difference was found in operation time, blood loss, postoperative hospital stay, number of N1 and N2 lymph nodes dissected, groups of N2 lymph node dissected, lymph node upstage rate or postoperative complications. The hospitalization cost of RATS was higher than that of VATS (P<0.001). Conclusion    In contrast with thoracoscopic lobectomy, robotic lobectomy has similar operative safety, and a thorough N1 lymphadenectomy in patients with clinical N0 lung malignant tumor≥3 cm.

Objective To summarize the diagnosis and treatment experience of portal vein aneurysm after liver transplantation. Methods Clinical data of two recipients with portal vein aneurysm after liver transplantation were retrospectively analyzed. Clinical features, diagnosis, treatment and prognosis were summarized based on literature review. Results Both two cases were diagnosed with intrahepatic portal vein aneurysm complicated with portal vein thrombosis and portal hypertension after liver transplantation. Case 1 was given with targeted conservative treatment and he refused to undergo liver retransplantation. Physical condition was worsened after discharge, and the patient eventually died from liver graft failure, kidney failure, lung infection, and septic shock. Case 2 received high-dose glucocorticoid pulse therapy, whereas liver function was not improved, and the patient was recovered successfully after secondary liver transplantation. Conclusions Long-term complication of portal vein aneurysm (especially intrahepatic type) after liver transplantation probably indicates poor prognosis. Correct understanding, intimate follow-up and active treatment should be conducted. Liver retransplantation may be a potential treatment regimen.

Immune checkpoint inhibitors (ICIs) have ushered in a new era of tumor treatment; however, immunotherapy-related adverse events are critical issues that restrict the clinical application of ICIs and have attracted wide attention. The liver is one of the target organs that is easily affected. With the progress in research, scholars have found that besides hepatocytes, intrahepatic and extrahepatic bile ducts can also be attacked by the immune system, leading to the disease known as immune-related cholangitis. This article reviews the research advances in ICI-related cholangitis by summarizing related articles, in order to preliminarily reveal its clinical, pathological, and imaging features and provide clues for early identification, standard treatment, and subsequent research.