Objective To investigate the therapeutic effect of traditional Chinese medicine (TCM) on portal vein thrombosis (PVT) in patients with liver cirrhosis and its medication characteristics. Methods A retrospective analysis was performed for 89 patients with liver cirrhosis and PVT who were hospitalized and treated in Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, and according to whether TCM treatment was applied in combination, they were divided into TCM group with 59 patients and control group with 30 patients. Related data were collected for the two groups, including demographic data, laboratory examination, radiological examination, gastroscopy, history of surgery, portal hypertension-related complications, medication, and follow-up data. The independent samples t -test was used for comparison of normally distributed continuous data between two groups, and the Mann-Whitney U rank sum test was used for comparison of non-normally distributed continuous data between two groups; the chi-square test or the Fisher's exact test was used for comparison of categorical data between two groups. An ordinal polytomous Logistic regression analysis was used for multivariate analysis. TCM Inheritance Computing Platform (V3.0) was used to perform a drug effect cluster analysis of TCM prescriptions. Results The multivariate logistic regression analysis showed that esophageal and gastric varices (odds ratio [ OR ]=3.144, 95% confidence interval [ CI ]: 1.221-8.094), PVT involving the portal vein (PV) and the superior mesenteric vein (SMV) ( OR =51.667, 95% CI : 3.536-754.859), PVT involving PV+spleen vein (SV)+SMV ( OR =13.271, 95% CI : 2.290-76.928), cavernous transformation of the portal vein ( OR =11.896, 95% CI : 1.172-120.696), and TCM intervention ( OR =0.348, 95% CI : 0.129-0.938) were influencing factors for the outcome of PVT in liver cirrhosis. Follow-up results showed that compared with the control group, the TCM group had a significantly lower progression rate (16.95% vs 56.67%, P < 0.001) and a significantly lower incidence rate of variceal rupture and bleeding (8.47% vs 33.33%, P < 0.001). Effective TCM drugs with a relatively high frequency of use included deficiency-tonifying drugs (359 times, 34.6%), blood-activating and stasis-resolving drugs (202 times, 19.5%), and diuresis-inducing and dampness-draining drugs (180 times, 17.3%); the TCM drugs with a relatively high frequency of use included Astragalus membranaceus (57 times, 8.7%), Angelica sinensis (50 times, 7.6%), and leech (48 times, 7.3%); TCM drug combinations with a relatively high frequency of use included Astragalus membranaceus+Angelica sinensis, Astragalus membranaceus+leech, Angelica sinensis+leech, and Astragalus membranaceus+Angelica sinensis+leech. Conclusion Qi-tonifying, blood-activating, and stasis-breaking drugs, such as Astragalus membranaceus, Angelica sinensis, and leech, can promote the stabilization or recanalization of PVT in liver cirrhosis and reduce the incidence rate of bleeding events due to portal hypertension.

Objective:To identify clinical features,possible risk factors and treatment related to rituximab-associated interstitial pneumonia(RTX-IP). Methods:The clinicopathological characteristics,immune phenotype and treatment of six patients with diffuse large B-cell lymphoma(DLBCL)develped after receiving R-CDOP treatment were retrospectively analyzed. Results:Six patients had agranulocytosis or granulocytopenia within 1 week before RTX-IP diagnosis,and the median interval time was 3 courses of treatment.All six patients had double-expressor lymphoma(DEL)or triple-expressor lymphoma(TEL).Of the six patients,four had germinal-center B-cell-like lymphoma(GCB),and two had non-GCB.The expression of Ki-67 was＞70％,except for one patient with transformed lymphoma(TL).After treatment with methylprednisolone for about 1 week,all patients'chest CT showed inflammatory absorption.However,one patient developed pneumocystis carinii pneumonia during the process of hormone reduction,and recovered after 27 days of comprehensive treatment with hormones and anti-pneumocystosis therapy.All patients received CDOP regimen(a total of 8 courses)for the treatment of the primary disease,and the process was smooth. Conclusion:R-CDOP regimen may lead to a high incidence of RTX-IP in DLBCL patients(30.0％).The DLBCL patients with DEL or TEL,GCB subtype,TL and high Ki-67 expression were more liable to develop RTX-IP,and the recovery of agranulocytosis may be related to the pathogenesis of RTX-IP.High-resolution CT scan can provide valuable evidence for early diagnosis of RTX-IP.Metagenomic next-generation sequencing(mNGS)helps to distinguish IP from pathogen infections.High dose of glucocorticoids is effective treatment strategy.At the same time,it is necessary to strengthen the prevention and treatment of infection in the process of glucocorticoids application.

Objective:To use metagenomic sequencing to compare the differences in intestinal microbiota species and metabolic pathways in patients with hepatitis B cirrhosis with or without ascites and further explore the correlation between the differential microbiota and clinical indicators and metabolic pathways.Methods:20 hepatitis B cirrhosis cases [10 without ascites (HBLC-WOA), 10 with ascites (HBLC-WA), and 5 healthy controls (HC)] were selected from the previously studied 16S rRNA samples. Metagenome sequencing was performed on the intestinal microbiota samples. The Kruskal-Wallis rank sum test and Spearman test were used to identify and analyse differential intestinal microbiota populations, metabolic pathways, and their correlations.Results:(1) The overall structure of the intestinal microbiota differed significantly among the three groups ( R = 0.19, P = 0.018). The HC group had the largest abundance of Firmicutes and the lowest abundance of Proteobacteria at the genus level. Firmicutes abundance was significantly decreased ( Pfdr < 0.01), while Proteobacteria abundance was significantly increased ( Pfdr < 0.01) in patients with cirrhosis accompanied by ascites; (2) LEfSe analysis revealed that 29 intestinal microbiota (18 in the HBLC-WA group and 11 in the HBLC-WOA group) played a significant role in the disease group. The unclassified Enterobacteriaceae and Klebsiella species in the HBLC-WA group and Enterobacteriaceae in the HBLC-WOA group were positively correlated with the Child-Turcotte-Pugh (CTP) score, prothrombin time, and international normalized ratio score and negatively correlated with albumin and hemoglobin levels ( P < 0.05). Escherichia and Shigella in the HBLC-WA group were positively correlated with CTP scores ( P < 0.05); (3) The correlation analysis results between the KEGG pathway and 29 specific intestinal microbiota revealed that Enterobacteriaceae and arachidonic acid, α-linolenic acid, glycerolipid metabolism, and fatty acid degradation were positively correlated in the lipid metabolism pathway, while most Enterobacteriaceae were positively correlated with branched-chain amino acid degradation and negatively correlated with aromatic amino acid biosynthesis in the amino acid metabolic pathway. Conclusion:A significant increment of Enterobacteriaceae in the intestines of HBLC-WA patients influenced hepatic reserve function and was associated with amino acid and lipid metabolic pathways. Therefore, attention should be paid to controlling the intestinal microbiota to prevent complications and improve the prognosis in patients with hepatitis B cirrhosis, especially in those with ascites.

Objective:To investigate the expression levels of serum calcitonin (CT) and osteoponin (OPN) in peripheral blood of patients with atrial fibrillation (AF) and their relationship with AF.Methods:A case control study was conducted, 160 AF patients treated in Shaanxi Provincial People's Hospital from June 2020 to December 2021 were selected as case group, and 160 healthy people in the same period were selected as control group. The expression levels of serum CT and OPN in the two groups were analyzed retrospectively, and the correlation between them and AF was analyzed. The value of CT and OPN levels in predicting the occurrence of AF was analyzed by receiver operating characteristic (ROC). Kappa consistency test was used to analyze the efficacy of the combination of them in predicting the occurrence of AF.Results:The serum calcitonin level ((13.5±3.2) ng/L) in the case group was lower than that in the control group ((17.3±3.1) ng/L), and the osteopontin level ((53.8±8.2) μg/L) was higher than that of the control group ((44.1±6.8) μg/L), the difference between the two groups was statistically significant ( t=10.79, P<0.001; t=11.50, P<0.001). The results of binary logistic regression analysis showed that serum calcitonin was the protective factor of atrial fibrillation ( OR=0.723, 95% CI: 0.661-0.790, P<0.001), and osteopontin was the risk factor ( OR=1.183, 95% CI: 1.131-1.237, P<0.001). ROC analysis showed that the area under curve (AUC) of CT, OPN and their combination in predicting AF were 0.794, 0.824, and 0.892, respectively. The predictive critical value for serum CT was <15.0 ng/L and >48.5 μg/L for OPN. The sensitivity, specificity of the combination in AF prediction were 67.50% and 93.75% respectively, and Kappa value was 0.613. Conclusion:The expression of serum CT and OPN was abnormal in patients with atrial fibrillation. The prediction of AF by combined examination of the two had a high degree of consistency with the actual results, which could provide reference for early diagnosis and treatment of AF. However, the rate of missed diagnosis was relatively high, which needs attention in clinical application.

Metformin is currently a strong candidate anti-tumor agent in multiple cancers. However, its anti-tumor effectiveness varies among different cancers or subpopulations, potentially due to tumor heterogeneity. It thus remains unclear which hepatocellular carcinoma (HCC) patient subpopulation(s) can benefit from metformin treatment. Here, through a genome-wide CRISPR-Cas9-based knockout screen, we find that DOCK1 levels determine the anti-tumor effects of metformin and that DOCK1 is a synthetic lethal target of metformin in HCC. Mechanistically, metformin promotes DOCK1 phosphorylation, which activates RAC1 to facilitate cell survival, leading to metformin resistance. The DOCK1-selective inhibitor, TBOPP, potentiates anti-tumor activity by metformin in vitro in liver cancer cell lines and patient-derived HCC organoids, and in vivo in xenografted liver cancer cells and immunocompetent mouse liver cancer models. Notably, metformin improves overall survival of HCC patients with low DOCK1 levels but not among patients with high DOCK1 expression. This study shows that metformin effectiveness depends on DOCK1 levels and that combining metformin with DOCK1 inhibition may provide a promising personalized therapeutic strategy for metformin-resistant HCC patients.
Animals ; Antineoplastic Agents/therapeutic use* ; Carcinoma, Hepatocellular/metabolism* ; Cell Line, Tumor ; Clustered Regularly Interspaced Short Palindromic Repeats ; Genome ; Humans ; Liver Neoplasms/metabolism* ; Metformin/therapeutic use* ; Mice ; Phosphorylation ; Synthetic Lethal Mutations ; Transcription Factors/metabolism* ; rac GTP-Binding Proteins/metabolism*

Objective:To study the real-world outcome of China FDA-approved Sofosbuvir (SOF)/Velpatasvir (VEL) in Northwest China.Methods:In this multicenter, prospective, real-world cohort study, we recruited patients from 10 sites from Northwest China, who were chronically infected with HCV GTs 1-6 from 06/2018 to 09/2019. Patients received SOF (400mg)/VEL (100mg) for 12 weeks, and with ribavirin 900-1200 mg for GT3 cirrhosis and for any genotype decompensated cirrhosis. The primary endpoint was sustained virological response at 12-weeks post-treatment (SVR12) and safety. The secondary endpoint was the change of liver function after the achievement of SVR12.Results:Totally, 143 patients were enrolled in the study, four patients were lost to follow-up and one died during the follow-up, 138 patients were included in per-protocol analysis. Of the 138 patients, the mean age 53 years, 53.6% male, 94.2% Han nationality, 53.6% liver cirrhosis, 10.1% HBsAg +, 6.5% renal dysfunction, 5.1% treatment-experienced, and 16.7% patients received ribavirin treatment. The genotype distribution was as follows: 35.5% GT1, 42.8% GT2, 15.9% GT3, and 5.8% un-typed. The SVR12 rate was 96.5% (138/143, 95% CI: 93.5%-99.6%) for intention-to-treat analysis, and in per-protocol analysis, all 138 patients obtained SVR12 (100%). Compared with baseline, the serum total bilirubin, ALT and AFP levels decreased (all P < 0.05), as well as increased ALB and platelet count (all P < 0.001) at post-treatment 12-weeks. Overall adverse events (AEs) rate is 29.0%, and the most common AEs were anemia (14.5%) and fatigue (8.0%). Severe side effects (edema and fatigue) occurred in 2 patients, one of whom needed a short-term interruption of treatment due to fatigue. Conclusion:In this real-world cohort study, 12-week SOF/VEL regimen with or without ribavirin achieved high SVR12 rates (96.5%-100% overall) with excellent safety profile among patients with HCV GT1/2/3 infection including patients with GT3 and cirrhosis, and led to improvement of liver function.

Objective To study the role of MDCT with 3D fusion images in the preoperative evaluation of pancreaticoduodenectomy.Methods 37 patients who underwent pancreaticoduodenectomy from March 2016 to May 2018 in the Affiliated Wuxi No.2 People's Hospital of Nanjing Medical University were included in this retrospective study.All patients underwent a dual-phase enhanced MDCT before operation.The volume data of enhanced MDCT were transmitted to a dedicated CT post-processing workstation.The 3D images,including the tumor,pancreas,portal vein system,arterial system,pancreatic and biliary tract,were reformatted respectively before the fusion imaging.Two reviewers analyzed the tumor location and its spatial relations with the pancreaticobiliary system,peripancreatic vessels and vascular variations by means of zooming,rotating,splitting and transparent displaying on fusion images.Then,the assessed items were compared to the surgical and pathological findings.Results The 3D fusion images of 37 patients in this study depicted the tumor,pancreas,peripancreatic vessels and pancreatic and biliary tract clearly.Compared with the intraoperative and pathological findings,the accuracy of both tumor detection and localization with the 3D fusion images was 100％.To compare the intraoperative findings,visualization and variation detection of the celiac,splenic,common hepatic,gastroduodenal,hepatic,and superior mesenteric arteries,and the superior mesenteric and portal veins were all 100％.Visualizations of the anterior superior pancreaticoduodenal artery (ASPDA),posterior superior pancreaticoduodenal artery (PSPDA),inferior pancreaticoduodenal artery (IPA) and dorsal pancreatic artery (DPA) were 85.7％,82.8％,72.2％ and 75.8％,respectively.Conclusion The MDCT 3D fusion imaging technology allowed one stop preoperative assessment of pancreaticoduodenectomy,especially in clearly outlining the tumor location and its spatial relations with the surrounding surgical anatomies before surgery.

Objective: To evaluate the effect of docosahexaenoic acid (DHA) on microglial activation during oxygen-glucose deprivation and restoration (OGD/R) injury. Methods: N9 microglia were inoculated in 96-well culture plates at a density of 10⁴ cells/well for 3-5 days and divided into 3 groups (n=18 each) using a random number table method: control group (group C), group OGD/R and DHA+ OGD/R group. The cells were cultured for 24 h in an incubator at 37 ℃ (95% air-5% CO₂) in group C. In OGD/R and DHA groups, the culture medium was replaced by glucose-free culture medium, the cells were cultured for 12 h in an incubator at 37 ℃ (95% N₂-5% CO₂), and then cells were returned to the normal culture medium and cultured for 24 h in an incubator at 37 ℃ (95% air-5% CO₂) to establish the OGD/R injury model. The cells in group DHA were incubated with 25 μmol/L DHA at 12 h before OGD/R. The cell viability was detected using the methyl thiazolyl tetrazolium assay, the activity of lactate dehydrogenase (LDH) was measured by using chemical colorimetric method, activated microglia were counted by immunofluorescence staining, the expression of microglia activation marker iba-1 was detected by Western blot, and the concentrations of tumor necrosis factor-α (TNF-α), interleukin 6 (IL-6) and IL-4 and IL-10 in culture medium were determined using enzyme-linked immunosorbent assay. Results: Compared with the group C, the cell viability was significantly decreased, the LDH activity was increased, the number of activated microglia was increased, and the expression of iba-1 was up-regulated in OGD/R and DHA+ OGD/R groups, the concentrations of TNF-α and IL-6 were significantly increased in group OGD/R, and the concentrations of TNF-α, IL-6, IL-4 and IL-10 were significantly increased in group DHA+ OGD/R (P<0.05). Compared with group OGD/R, the cell viability was significantly increased, the LDH activity was decreased, the number of activated microglia was decreased, the expression of iba-1 was down-regulated, TNF-α and IL-6 concentrations were decreased, and IL-4 and IL-10 concentrations were increased in group DHA (P<0.05). Conclusion The mechanism by which DHA reduces OGD/R injury may be related to inhibiting activation of microglia and to reducing inflammatory responses.

Objective: To describe the MICM (morphology, immunology, cytogenetics and molecular biology) characteristics of a case of acute myelomonocytic leukemia M 4C . Methods: The medical history data of the case of M 4C admitted to our hospital was reviewed. The results of bone marrow cell morphology, cytochemical stains, bone marrow biopsy, immunophenotype, cytogenetics, molecular test and NGS (next-generation sequencing) of the case were analyzed. Results: The bone marrow smear showed markedly active proliferation of bone marrow cells in which the myelomonocytic cells accounted for 85.6%. Cytochemical stains showed peroxidase (POX) stain partially and weakly positive; specific esterase AS-DCE partially positive; non-specific esterase α-NBE partially positive and smothered by sodium fluoride; non-specific esterase AS-DAE partially positive and smothered by sodium fluoride. Bone marrow biopsy showed hyperproliferative cells and diffused hyperplasia of blasts. Immunophenotype analysis showed that the abnormal cell population was positive for CD11B, CD64, CD56, cMPO, CD33, CD41, CD61, CD38 and CD58, but negative for CD13, CD34, CD117, CD7, CD123, HLA-DR, CD10, CD19, CD20, CD2, CD14, CD235, CD15, CD303, CD304, CD25, cCD79a, cCD3, cCD22, CD1a and TDT. Cytogenetic analysis showed 47, XY, t(9;11) (p22;q23),+mar. The molecular test for leukemia showed MLLT3/KMT2A gene rearrangement. NGS showed NRAS and TET2 mutation. The case was finally diagnosed as AML (acute myelomonocytic leukemia) M 4C with t(9;11)(p22;q23), MLLT3-KMT2A. Conclusion Leukemia M 4C may show the characteristics of both granulocytes and monocytes with complex morphological features. The combined examination of MICM should be necessary for the diagnosis of M 4C with great significance.

Objective To test the value of miRNA-30c(miR-30c)in early diagnosis of gastric cancer. Methods Serum miR-30c expression levels were detected by using quantitative real-time polymerase chain reaction in 80 patients with advanced gastric cancer, 35 patients with early stage gastric cancer and 35 healthy controls in the Affiliated People's Hospital of Inner Mongolia Medical University from August 2014 to August 2017. The receiver operating characteristic (ROC) curves and the area under the curve (AUC) were analyzed to test the efficacy of the miR-30c in distinguishing advanced gastric cancer, early stage gastric cancer and healthy controls. Results The expression level of serum miR-30c in advanced gastric cancer (0.45±0.11) was lower than that in early stage gastric cancer (0.54±0.15) (t = 5.2, P < 0.05). Compared with the healthy controls (0.61±0.12), miR-30c was down-expressed in the serum of early stage gastric cancer patients(t=6.7,P<0.05).Compared with the traditional tumor markers,the AUC of miR-30c was the biggest (0.92±0.03) in early stage and advanced gastric cancer groups, and the sensitivity and specificity in the diagnosis of gastric cancer were 90 % and 84 %, respectively. The AUC of miR-30c was 0.87±0.04 in early stage gastric cancer and healthy controls, and the sensitivity and specificity in the diagnosis of gastric cancer were 70 % and 86 %, respectively. Conclusion miR-30c might be used as a potential serum biomarker for the early diagnosis of gastric cancer.