[Comparison of clinical features of JAK2V617F gene mutation and non-mutation in patients with Budd-Chiari syndrome].

Objective: To investigate the clinical features of JAK2V617F gene mutation and non-mutation in patients with Budd-Chiari syndrome (BCS). Methods: 17 and 127 BCS cases with JAK2V617F gene mutation (mutation group) and non-gene mutation (non-mutation group) who were continuously treated with interventional therapy between January 2016 to December 2020 in the Affiliated Hospital of Xuzhou Medical University were selected as the research object for a comparative study. The hospitalization and follow-up data of the two groups were analyzed retrospectively, and the deadline for follow-up was June 2021. Quantitative data group differences were analyzed using the independent sample t-test and Wilcoxon rank sum test. Qualitative data group differences were analyzed with χ2 test or Fisher's exact test. Mann-Whitney U test was used to analyze the differences between groups in rank data. Kaplan-Meier method was used to calculate the patient survival and recurrence rate. Results: Age [(35.41±17.10) years vs. (50.09±14.16) years, t=3.915, P<0.001], time of onset (median duration: 3 months vs. 12 months), and the cumulative survival rate (65.5% vs 95.1%; χ2=5.21, P=0.022) were lower in mutation than non-mutation group. Aaspartate aminotransferase, alanine aminotransferase, prothrombin time, Child-Pugh score, Rotterdam score, Model for End-stage Liver Disease score, hepatic vein thrombosis incidence, and the cumulative recurrence rate after intervention were higher in mutation than non-mutation group. The above all indexes had statistically significant differences (P<0.05) between the groups. Conclusion: Younger age, acute onset, severe liver injury, high incidence of hepatic vein thrombosis, and poor prognosis are the features of patients with BCS with JAK2V617F gene mutation than non-mutation.

[Analysis of curative efficacy of transjugular intrahepatic portosystemic shunt using viabahn stent in the treatment of Budd-Chiari syndrome with extensive hepatic vein occlusion].

Objective: To investigate the efficacy of transjugular intrahepatic portosystemic shunt (TIPS) using viabahn stent in patients with Budd-Chiari syndrome (BCS) with extensive hepatic vein occlusion. Methods: Technical success rates, portal pressure gradient (PPG), complications and shunt patency rate of 25 cases with BCS with extensive hepatic vein occlusion treated by TIPS using viabahn stent were retrospectively analyzed. Color Doppler ultrasound was used for postoperative follow-up. Patency rates were evaluated by Kaplan-Meier curve. Results: The technical success rate of TIPS was 100%. Mean PPG decreased from (22.7 ± 6.2) mmHg preoperatively to (9.7 ± 2.6) mmHg postoperatively (t = 9.58, P < 0.05). Hepatic encephalopathy incidence was 8.0% (2/25), and there were no complications such as intra-abdominal hemorrhage. Twenty-five cases were followed up for 1 to 39 ( mean 19.0 ± 11.9) months, and one patient died of liver failure three months after interventional treatment. The primary patency rates at 1, 2, and 3 years after interventional treatment were 91.3%, 91.3%, and 78.2%, respectively, while the repatency rates were 100%, 92.9%, and 92.9%, respectively. Conclusion: TIPS using viabahn stent can bring better short-term and mid-term curative efficacy in treatment of BCS with extensive hepatic vein occlusion.

[Analysis of treatment modalities and prognosis of patients with gallbladder cancer in China from 2010 to 2017].

Objective: To evaluate the clinical characteristics and prognosis of gallbladder cancer (GBC) patients in China. Methods: This retrospective multicenter cohort study enrolled 3 528 consecutive GBC patients diagnosed between January 2010 to December 2017 in 15 hospitals from 10 provinces. There were 1 345 (38.12%) males and 2 183 (61.88%) females.The age of diagnosis was (63.7±10.8) years old (range: 26 to 99 years old) .There were 213 patients (6.04%) in stage 0 to Ⅰ, whereas 1 059 (30.02%) in stage Ⅱ to Ⅲ, 1 874 (53.12%) in stage Ⅳ, and 382 (10.83%) unavailable. Surgery was performed on 2 255 patients (63.92%) . Three hundred and thirty-six patients received chemotherapy or radiotherapy (9.52%; of which 172 were palliative); 1 101 (31.21%) received only supportive treatment.The patient source, treatment and surgery, pathology, concomitant gallstone, and prognosis were analyzed. Results: Among the 3 528 GBC patients, 959 (27.18%) were from East China, 603 (17.09%) from East-North China, 1 533 (43.45%) from Central China, and 433(12.27%) from West China. Among the 1 578 resectable tumor, 665 (42.14%) underwent radical surgery, 913 (57.86%) underwent surgery that failed to follow the guidelines.Eight hundred and ninety-one (56.46%) patients were diagnosed before surgery, 254 (16.10%) during surgery, and 381 (24.14%) after surgery (time point of diagnosis couldn't be determined in 52 patients) .Among the 1 578 patients with resectable tumor, 759 (48.10%) had concomitant gallstone.Among the 665 patients underwent radical surgery, 69 (10.4%) showed positive resection margin, 510 (76.7%) showed negative resection margin, and 86 (12.9%) unreported margin status.The 5-year overall survival rate (5yOS) for the 3 528-patient cohort was 23.0%.The 5yOS for patients with resectable tumor was 39.6%, for patients with stage ⅣB tumor without surgery was 5.4%, and for patients with stage ⅣB tumor underwent palliative surgery was 4.7%. Conclusions: More than half GBC patients in China are diagnosed in stage Ⅳ.Curative intent surgery is valuable in improving prognosis of resectable GBC.The treatment of GBC needs further standardization.Effective comprehensive treatment for GBC is in urgent need.

[Preliminary application of transjugular intrahepatic portosystemic shunt in individualized treatment of patients with cirrhotic portal hypertension complicated with refractory ascites and variceal hemorrhage].

Objective: To investigate the feasibility, efficacy and safety of transjugular intrahepatic portosystemic shunt (TIPS) in the individualized treatment of patients with refractory ascites and variceal hemorrhage caused by portal hypertension. Methods: Prospective study of clinical data of 47 patients with portal hypertension and refractory ascites and variceal bleeding admitted to the Affiliated Hospital of Xuzhou Medical University from August 2017 to December 2018, 26 males and 21 females, aged 23-75 (52±14) years old. The Viabahn stent was used to control the diameter of the shunt and the preoperative interval of PPG after individualized TIPS was determined according to the preoperative liver function Child-Pugh classification. The PPG of the Child A and B patients was <10 mm Hg (1 mmHg=0.133 kPa), Child-Pugh C grade patients with postoperative PPG interval values of 12 to 15 mmHg. The success rate, hemostasis rate, ascites remission rate, and complication rate were recorded. Results: Forty-seven patients were with a success rate of 100%, and there was no surgically related fatal complications. The portal pressure gradients of patients with Child-Pugh A, B and Child-Pugh C were reduced from preoperative (22.5±5.4), (24.4±2.6) mm Hg to postoperative (8.8±2.5), (13.2±1.1) mm Hg (all P<0.05). All the patients were followed up for 6 to 24 months, with a median follow-up of 13 months. The success rate of hemostasis in patients with upper gastrointestinal bleeding was 93.5% (29/31), the remission rate of patients with refractory ascites was 14/16, the postoperative rebleeding rate was 6.5% (2/31), the incidence of hepatic encephalopathy was 8.5% (4/47), and the shunt disorder was 2.1% (1/47). Conclusion: The use of Viabahn stent for individualized TIPS in the treatment of portal hypertension with refractory ascites and variceal hemorrhage is feasible, and the clinical efficacy is affirmative, which can reduce the incidence of postoperative hepatic encephalopathy and shunt dysfunction.

[Progress of application for enhanced recovery after surgery in pancreaticoduodenectomy].

Due to the large surgical trauma and postoperative complications, the perioperative management of pancreaticoduodenectomy has been one of the urgent problems to be solved by the surgeons. With the development of modern medicine, enhanced recovery after surgery (ERAS) comes into being, basing on anti-stress mechanism and multi-disciplinary team, and the perioperative management of pancreaticoduodenectomy has been optimized and improved continuously. The surgeons through a range of measures that had evidence-based medicine basis to mitigate the extent of surgical trauma stress, reduce the incidence of postoperative complications, shorten patient recovery time previously healthy state, and achieve maximize benefit for patients. Currently, the ERAS application in the specific aspects of pancreaticoduodenectomy remains contentious. However, with the emergence of evidence-based medicine, ERAS is constantly being refined. Therefore, this article combined with ERAS guidelines and expert consensus is of great significance to deepen the research and understanding of ERAS in pancreaticoduodenectomy.

[Combined multiple artery-first approach to pancreatoduodenectomy].

Objective: To investigate the clinical application of combined multiple artery-first approach to pancreatoduodenectomy. Methods: The clinical data of 53 patients who were diagnosed with peripancreatic head tumor at Department of Biliary-Pancreatic Surgery of Second Affiliated Hospital of Harbin Medical University between June 2013 and June 2015 was retrospectively analyzed.Pancreatic enhanced CT scan, magnetic resonance cholangiopancreatography, ultrasonography and tumor marker detection were applied for all the patients preoperatively.The 53 patients were operated by combined multiple artery-first approach(superior+ posterior approach, superior+ inferior approach, posterior+ inferior approach, superior+ posterior+ inferior approach) according to individualized therapeutic concept.And 42 patients underwent pancreatoduodenectomy, 9 patients underwent palliative operation and 2 patients just received exploratory operation. Results: Forty-two peripancreatic head tumor patients underwent pancreatoduodenectomy by applying combined multiple artery-first approach.The median operation time and intraoperative blood loss were (5.4±3.1)hours and (366±297)ml and the harvested lymph node and duration of hospital stay were 19±5 and (14.0±5.6)days.Nine patients underwent "total mesopancreas excision" and the rate of postoperative pancreatic fistula and R0 resection were 38.1% and 88.1%. Anomalous origin hepatic right artery was detected in one patients during the operation and no death occurred within 30 days postoperatively. Conclusion: According to the tumor location and patient's condition, individualistically applying combined multiple artery-first approach can reduce intraoperative blood loss, terminate unnecessary surgery, detect anomalous origin artery, make the tumor resection more radical and pancreatoduodenectomy more safety.

Molecular dynamics study of three amino acids as corrosion inhibitor for copper in hydrochloric acid solution.

Molecular dynamics (MD) simulation is used to study the corrosion inhibition mechanism of cysteine (Cys), glutamic (Glu) and glycine (Gly) for copper in hydrochloric acid solution. The adsorption energy and radial distribution function results show that all three amino acids can spontaneously adsorb on Cu (111) surface by chemical adsorption. The absolute value of adsorption energy and intensity is Cys > Glu > Gly. The diffusion coefficient and relative concentration curve show that all the three amino acids can inhibit the diffusion and aggregation ability of corrosion particles, so the three amino acids not only can slow down the aggregation of corrosive particles, but also effectively repel corrosive particles to protect the substrate. The inhibition ability obtained by the MD simulation shows the trend of Cys > Glu > Gly, which is consistent with the experimental results. The inhibition efficiency is determined by both the adsorption strength on the substrate surface and inhibition ability for the diffusion and aggregation ability of corrosion particles.

Induced liver allograft immunological tolerance in rats by intramuscular injection of recombinant adeno-associated virus-human cytotoxic T-lymphocyte-associated antigen-4 immunoglobulin (rAAV-hCTLA4Ig).

Induction of liver allograft immunological tolerance was performed in rats by intramuscular injection of recombinant adeno-associated virus-human cytotoxic T-lymphocyte-associated antigen-4 immunoglobulin (rAAV-hCTLA4Ig). Dark Agouti and Lewis rats were liver allograft donors and recipients, respectively, in four groups: (A) syngeneic control, (B) blank control, (C) rAAV-enhanced green fluorescent protein negative control, (D) rAAV-hCTLA4Ig. Gene transfers occurred 6 weeks before transplantation. Group D had a significantly longer liver graft survival time (> 100 days) than groups B (11.9 +/- 1.3 days) and C (11.6 +/- 1.1 days). Groups B and C showed severe rejection responses and large amounts of CD4(+) and CD8(+) T-lymphocyte infiltration, while only a mild response and few T-lymphocytes were observed in group D. There were no significant differences in interleukin-2 and interferon-gamma levels in liver grafts between groups D and C, but there were significant decreases in granzyme B and lymphotoxin beta levels in group D compared with group C. It is concluded that immunological tolerance to liver allograft could be achieved by gene transfer of rAAV-hCTLA4Ig through intramuscular injection.

Overexpression of a hematopoietic transcriptional regulator EDAG induces myelopoiesis and suppresses lymphopoiesis in transgenic mice.

Erythroid differentiation-associated gene (EDAG) is a hematopoietic tissue-specific gene that is highly expressed in the earliest CD34+ lin- bone marrow (BM) cells and involved in the proliferation and differentiation of hematopoietic cells. To investigate the role of EDAG in hematopoiesis, we established an EDAG transgenic mouse model driven by human CD11a promoter. The transgenic mice showed increased mortality with severe organ infiltration by neutrophils, and the homeostasis of hematopoiesis was broken. The myelopoiesis was enhanced with expansion of myeloid cells in BM, increased peripheral granulocytes and extramedullary myelopoiesis in spleen. In contrast to myeloid cells, the lymphoid commitment was severely impaired with the B lymphopoiesis blocked at the transition from pro/pre-B I to pre-B II stage in BM and T thymocytes development blocked at the most immature stage (DN I). Moreover, we showed that EDAG was a transcriptional regulator which had transactivation activity and regulated the expression of several key transcription factors such as PU.1 and Pax5 in transgenic hematopoietic stem cells. These data suggested that EDAG was a key transcriptional regulator in maintaining the homeostasis of hematopoietic lineage commitment.

A novel prognostic biomarker for cholangiocarcinoma: circRNA Cdr1as.

OBJECTIVE: Cholangiocarcinoma (CCA) is the second most common primary malignant hepatobiliary cancer worldwide. The circular RNA (circRNA) Cdr1as has been found to play critical roles in various cancers. However, the relationship between circRNA Cdr1as and CCA is still ambiguous. The aim of this study was to explore the expression level of Cdr1as in CCA and to further investigate the clinicopathological and prognostic value of Cdr1as. PATIENTS AND METHODS: We investigated the circRNA Cdr1as expression in 54 paired tumor and adjacent normal tissues of CCA patients by using quantitative Real-time PCR, and evaluated the relevance between Cdr1as expression level and the clinicopathological features. We further assessed the association of Cdr1as expression with overall survival and its prognostic efficacy. RESULTS: The expression of circRNA Cdr1as in tumor tissues was higher than that in adjacent normal tissues. The overexpression of Cdr1as was closely associated with the advanced TNM stage, lymph node invasion, and postoperative recurrence. The overall survival of CCA patients with high Cdr1as expression was worse than that of the CCA patients with low Cdr1as expression. According to multivariate analysis, the Cdr1as expression could be considered as an independent prognostic biomarker for cholangiocarcinoma with acceptable sensitivity and specificity. CONCLUSIONS: Our finding suggested that circRNA Cdr1as may serve as a potential vicious molecular biomarker to predict the aggressive tumor progression and worse prognosis for CCA patients.

Effect of PM2.5 mediated oxidative stress on the innate immune cellular response of Der p1 treated human bronchial epithelial cells.

OBJECTIVE: To investigate the effect of stimulation of Human Bronchial Epithelial Cells (HBEC) by Der p1 and PM2.5 on the expression of innate immune cell factors to find new therapeutic targets for treatment of bronchial asthma. MATERIALS AND METHODS: The Der p1 antigen exposure model in the HEBC line, 16HBE-14o, was established in vitro. PM2.5 at a concentration of 50 µM/cm2, was added to these cells for 0.5 h, 1 h, 2 h and 3 h. Cells were treated with the following reagents for the indicated times: 300 ng/mL Der p1 for 21 h, 50 µM/cm2 PM2.5 for 3 h, 10 mM Nac for 3 h and PM2.5 contamination for 3 h. The experiment was divided into five groups: control (group A), Der p1 exposure group (group B), PM2.5 treated group (group C), PM2.5+Der p1 exposure group (group D), Nac+PM2.5+Der p1 exposure group (group E). ELISA method was adopted to test the expression levels of malondialdehyde, IL-25, IL-33 and thymic stromal lymphopoietin (TSLP), and Real-time RT-PCT was used to measure IL-25, IL-33 and TSLP mRNA. RESULTS: The protein and mRNA levels of malondialdehyde, IL-25, IL-33 and TSLP in group D were significantly higher than those in the other groups, while the protein and mRNA levels of malondialdehyde, IL-25, IL-33 and TSLP in group E were significantly lower than those in group D (p<0.05). CONCLUSIONS: PM2.5 can enhance the Der p1 antigen-induced HBEC innate immune response through the expression of IL-25, IL-33 and TSLP, which may exacerbate the occurrence rate of bronchial asthma.

LncRNA CCAT1 as the unfavorable prognostic biomarker for cholangiocarcinoma.

OBJECTIVE: To investigate the expression of long noncoding RNA CCAT1 in cholangiocarcinoma (CCA) and to assess the CCAT1 expression as a prognostic biomarker for CCA. PATIENTS AND METHODS: The CCAT1 expression in tumor tissues and paired adjacent normal tissues from 91 CCA patients was detected by quantitative real-time PCR. The association of the CCAT1 expression with clinicopathological features of CCA patients and the prognostic value of the CCAT1 expression for overall survival was also evaluated by Kaplan-Meier, Cox regression model and ROC analysis. RESULTS: The CCAT1 expression was significantly upregulated in CCA tumor tissues compared with adjacent normal tissues. The CCAT1 expression was obviously associated with histological differentiation, lymph node invasion, and TNM stage. The overall survival of CCA patients with high CCAT1 expression was worse. Furthermore, the CCAT1 expression could be considered as an independent prognostic factor in predicting the overall survival for CCA patients. CONCLUSIONS: Our study showed that lncRNA CCAT1, which was upregulated and associated with aggressive malignant behavior, may serve as a novel prognostic biomarker and potential therapeutic target for cholangiocarcinoma.

Clinical application of solitaire AB stents in the embolization of intracranial aneurysms.

OBJECTIVE: To evaluate the clinical value of Solitaire AB stents in the embolization of intracranial aneurysms. PATIENTS AND METHODS: Solitaire AB stents were applied in treating 69 aneurysms in 65 patients. Among them, there were 67 "wide neck" aneurysms and two "narrow neck" aneurysms. Of the 69 aneurysms, there were 40 aneurysms in the posterior communicating artery, 13 in the ophthalmic artery segment, one in the cavernous segment of the internal carotid artery, three in the middle cerebral artery, one in the anterior communicating artery, eight in the vertebral artery, and three in the basilar artery. The treatment techniques used included transposition, parallel technique, post-release technique, and salvage stenting. RESULTS: Immediate angiographic results showed complete thrombosis in 63 cases, residual aneurysm neck in two cases and partial embolism in four cases. Intraoperative aneurysm rupture was found in two cases, of which bleeding was stopped with continued filling. Postoperative hydrocephalus cerebrospinal fluid shunt was performed in one case. Coil shift was observed in two cases. No further bleeding cases occurred during the clinical follow-up. Of 14 patients who had undergone angiographic follow-up, three cases had recurrence and one case received re-embolization. CONCLUSIONS: Solitaire AB stent is clinically feasible when applied for the embolization of intracranial aneurysms using multiple techniques and, thus, warrants clinical promotion.

The relative spatial distribution of in vitro-CFCs in the bone marrow, responding to specific growth factors.

Haemopoietic progenitor cells are stimulated by a range of growth factors which promote colony growth in culture. The progenitors are a part of an age-structured developmental hierarchy in the tissue. The growth factors, although overlapping in their effects, stimulate cells preferentially at different stages in this programme. Femoral bone marrow was fractionated into axial (close to the central venous sinus) and marginal (close to the bone surface) cells. Progenitors which responded to IL-3, GM-CSF, G-CSF, M-CSF and SCF were then assayed in soft agar cultures. Consequent plots of their spatial distributions showed that the more primitive cells in vitro (responding to IL-3) were concentrated close to the bone surface. The peak concentrations of cells responding primarily to growth factors with progressively more affinity to more mature progenitor cells correspondingly appeared progressively further from the bone surface and closer to the point of release at the central venous sinus. This suggests that the developmental/maturational process in haemopoiesis is accompanied by a progressive movement of cells from the bone surface towards the central axial regions of the bone cavities. The most primitive cells are however exposed, close to the centre of the cavity, by a combination of SCF and G-CSF (or by a 50-fold increase in G-CSF concentration alone). These results corroborate earlier data which indicate a developmental movement of cells from the centre of the marrow tissue towards the bone surface and back again, sequentially encountering a series of growth factors which promote their differentiation into mature cells, for release at the central venous sinus.

Apoptosis in bone marrow cells of mice with different p53 genotypes after gamma-rays irradiation in vitro.

Apoptosis is a physiological phenomenon occurring during embryonic development, T and B cell maturation, and endocrine-induced atrophy. It can be initiated by various agents and has been considered to be related to the expression of the oncosuppressor p53 gene. In this review, p53 gene-targeting mice were used to study the effect of p53 gene status on the induction of apoptosis in bone marrow cells by gamma-ray irradiation. The results showed that homozygous null (p53 -/-) murine bone marrow cells were more resistant to the induction of apoptosis by radiation than other genotypes (heterozygous, p53 +/- and wild type, p53 +/+). The percentage of apoptotic cells in p53 +/+ mice was about three times that in p53 -/- mice at 4 hr after 6 Gy gamma-irradiation, and the analysis of the apoptosis-characteristic DNA ladder further supported these findings. We found that the homozygous null mice also can undergo apoptosis after irradiation. This suggested that there is another independent apoptotic p53 gene mechanism in irradiated murine bone marrow cells. Thus, in murine bone marrow cells, both p53 gene-dependent and -independent apoptosis occurred after irradiation. In our previous work, an increase in survival of hemopoietic progenitor cells after irradiation in vitro in p53 gene deletion mice was observed. This increase is closely related to the inhibition of apoptosis in bone marrow cells in p53 gene deletion mice.

Apoptosis of lymphocytes in canine peripheral blood induced by shock vibration and its mechanism.

We investigated the mechanism of apoptosis induced by shock vibration in canine peripheral lymphocytes, the T-lymphocyte changes, and the expression of p53 and bax gene products related to apoptosis using the techniques of immuno- and enzyme cytochemistry. We noted obvious apoptosis after delivery of 80, 100, and 200 acceleration of gravity values (G values). The percentage of apoptotic lymphocytes was directly proportional to the G value. On the 3rd day after injury, the number of apoptotic lymphocytes reached the peak value, which was about 5 to 8 times the amount in the control group. On the contrary, on day 3 after injury, T lymphocytes decreased and were about 50% of the control group. On the other hand, we found that the percentage of p53 and bax-positive lymphocytes distinctly increased and, on the 3rd day after injury, their number was, respectively, about 2.3 and 1.8 times that in the control groups, suggesting that they may play an important role in lymphocyte apoptosis. The above-mentioned results provide an important basis for further study of the mechanism of shock-vibration injury, its prevention, and treatment.

Apoptosis of circulating lymphocytes induced by whole body gamma-irradiation and its mechanism.

We studied the apoptosis of mousecirculating lymphocytes and its mechanism induced by 2, 4, 6, and 8 Gy of whole-body gamma-irradiation and the expression of bax and bcl-2 gene products as related to apoptosis. We found that, in the early stage after irradiation (4th-7th day), the percentage of lymphocyte apoptosis increased rapidly. Four hours after 2, 4, 6, and 8 Gy of gamma-irradiation, the apoptotic lymphocytes were 2.6, 3.8, 5.5, and 10.4 times those in the controls, respectively. A good correlation was found between the intensity of apoptosis and the radiation dose. As the radiation dose increased, the absolute counts of peripheral lymphocytes decreased sharply; 4 hours after 2, 4, 6, and 8 Gy of gamma-irradiation, the lymphocyte counts were 82, 63, 47, and 22% of the controls, respectively. The peak value of lymphocyte apoptosis was observed on the 7th day after irradiation using the in situ terminal labeling method, and the apoptotic lymphocytes were found to be 16 times the number in the controls. These results were in accordance with those obtained by the May-Grünwald-Giemsa staining method. The absolute counts of peripheral lymphocytes dropped to their lowest value on the 7th day after irradiation, suggesting that lymphocyte apoptosis might be the major cause of lymphocytopenia in the early stage after irradiation. The abnormal expression of bax and bcl-2 gene products in irradiated lymphocytes was closely related to apoptosis in peripheral lymphocytes.