Long noncoding RNA FAM66C promotes tumor progression and glycolysis in intrahepatic cholangiocarcinoma by regulating hsa-miR-23b-3p/KCND2 axis.

Long noncoding RNAs (lncRNAs) are known to be the important regulators in cancer progression. However, the role of lncRNA FAM66C (FAM66C) is yet to be investigated in intrahepatic cholangiocarcinoma (ICC). This study aimed to investigate the effects and related mechanisms of FAM66C in ICC. Human ICC tissues and cell lines were collected. The expression levels of FAM66C, hsa-miR-23b-3p (miR-23b-3p), and KCND2 were detected by qRT-RCR. The transfection experiments were employed to measure the effect of FAM66C on cell viabilities, migration, and invasion in ICC cells by CCK-8, transwell assays. Glycolysis was investigated by glucose consumption, lactate production and ATP levels. The dual-luciferase reporter and RNA pull down assays were conducted as a means of confirming the interactions between FAM66C, miR-23b-3p, and KCND2. Furthermore, the levels of the EMT-associated proteins (KCND2, GLUT1, PKM2, and LDHA) in ICC cells were detected by western blot. FAM66C was increased in ICC tissues and cells, increased cell viability, glycolysis, migration and invasion, and decreased apoptosis were shown in FAM66C overexpressing cells. Mechanistic analyses revealed that FAM66C regulated the downstream target gene KCND2 by sponging miR-23b-3p. FAM66C effect on ICC was further validated in murine xenograft assays. FAM66C knockdown cells gave rise to tumors that were smaller in size, consistent with the role of FAM66C as a promoter of in vivo tumor growth. These data revealed that FAM66C was able to drive ICC tumor progression and glycolytic activity via the miR-23b-3p/KCND2 axis, indicating FAM66C may be a viable target for treating ICC.

[Intraoperative slide rail CT assistance in percutaneous sacroiliac joint screws for the treatment of pelvic posterior ring injury].

OBJECTIVE: To compare the clinical efficacy of intraoperative slide rail CT combined with C-arm X-ray assistance and just C-arm for percutaneous screw in the treatment of pelvic posterior ring injury. METHODS: A retrospective analysis was performed on the patient data of 76 patients with posterior pelvic ring injury admitted to the Department of Orthopedic Trauma from December 2018 to February 2022. Among them, 39 patients in the CT group were treated with C-arm combined with slide rail CT-assisted inline fixation including 23 males and 16 females with an average age of (44.98±7.33) years old;and the other 37 patients in the C-arm group were treated with intraline fixation treatment under only C-arm fluoroscopy including 24 males and 13 females with an average age of (44.37±10.82) years old. Among them, 42 patients with anterior ring fractures were treated with percutaneous inferior iliac spines with internal fixation (INFIX) or suprapubic support screws to fix the anterior pelvic ring. Postoperative follow-up time, operation time, complications of the two groups were compared. Results of Matta reduction criteria, Majed efficacy evaluation, the CT grading and the rate of secondary surgical revision were compared. RESULTS: The nailing time of (32.63±7.33) min in CT group was shorter than that of (52.95±10.64) min in C-arm group (t=-9.739, P<0.05). The follow-up time between CT group (11.97±1.86) months and C-arm group (12.03±1.71) months were not statistically significant(P>0.05). The postoperative complication rates between two groups were not statistically significant (χ2=0.159, P>0.05). Results of Matta reduction criteria (Z=2.79, P<0.05), Majeed efficacy evaluation(Z=2.79, P<0.05), CT grading (Z=2.83, P<0.05) in CT group were better than those in C-arm group(P<0.05); the secondary surgical revision rate in the CT group was significantly lower than that in the C-arm group (χ2=5.641, P<0.05). CONCLUSION: Compared with traditional C-arm fluoroscopy, intraoperative slide rail CT combined with C-arm assisted percutaneous sacroiliac joint screw placement surgery has the characteristics of short operation time, high accuracy and safety, and significant decrease in postoperative secondary revision rate, and is one of the effective methods for re-establishing the stability of the posterior ring of pelvic fracture.

Effects of immunosuppressive agents on Th17 cells involved in transplantation.

The lymphocyte-derived helper T (Th) cells are critical regulators of the adaptive immune response and are associated with inflammatory disease. The most recently recognized Th-cell lineage, Th17, plays an important role in host defense against extracellular pathogens by secreting the proinflammatory cytokine, interleukin 17, and recruiting reactive oxygen species (ROS)-producing monocytes to the site of infection. However, accumulating evidence has implicated Th17-cell dysregulation as an underlying cause for some immune-related pathogenic conditions, including allograft rejection. Recent studies of human transplant patients have indicated that Th17 cells exhibit resistance to current immunosuppressive therapies that would otherwise prevent allograft rejection. In this review, we will discuss the most current research findings related to Th17-cell function in various kinds of allografts.

Unusual presentation of congenital radioulnar synostosis with osteoporosis, fragility fracture and nonunion: A case report and review of literature.

BACKGROUND: Congenital radioulnar synostosis (CRUS) is a rare deformity of the upper extremity. It is characterized by loss of rotation of the involved forearm and functional limitations in daily activities. No studies on CRUS with osteoporosis have been reported to date, and osteoporosis is usually recognized as an important dimension of genetic disorder in children. We discuss the possible relationship among this disorder, osteoporosis and fracture nonunion, investigate the strict surgical indications and recommended treatments. CASE SUMMARY: A 14-year-old male patient with bilateral CRUS with osteoporosis, fragility fracture and nonunion of fractures in ulna and radius presented our institution for further treatment, complaining of limitation in rotation. The bone mineral density of the hip and lumbar spine was 0.687 g/cm2 and 0.705 g/cm2, respectively, and the Z-score for both was -2.1, which revealed osteoporosis and a high risk of fracture. Tow serum bone turnover markers indicated an imbalance of bone metabolism. Reoperation for ulna fracture with autogenous bone grafting and a postoperative physiotherapy program were adopted rather than the separation of pathological synostosis. Radiological examination, observational posture assessment and limb function scale were evaluated before and 1 year after surgery. At 1 year, the fracture nonunion had almost recovered, forearm movement function on the fracture side was restored, and function on the healthy side was significantly improved compared with that before rehabilitation. CONCLUSION: Surgical indications for CRUS vary from person to person. Surgery should not be the first choice of treatment, and physiotherapy is not inferior to surgical treatment.

Sinusoidal Endothelial Cell Progenitor Cells Promote Tumour Progression in Patients with Hepatocellular Carcinoma.

OBJECTIVE: As sinusoidal endothelial cell progenitor cells (SEPCs) play a significant role in liver regeneration, it is necessary to elucidate whether SEPCs participate in tumour progression of hepatocellular carcinoma (HCC). METHODS: A total of 45 patients with primary HCC who underwent liver resection were included in this study. The liver tumours were removed from the patients, and partial tissues were prepared to identify SEPCs through double staining of CD133/CD45 and CD133/CD31 at the same location. Blood samples were collected to examine liver function parameters and tumour markers. The demographics and clinicopathological characteristics of the patients were collected for correlation analysis with SEPCs. RESULTS: SEPCs were observed in several blood vessels within the HCC nodules of all 45 patients, but no SEPCs were detected in the tumour-adjacent tissues. The number of SEPCs was correlated with the expression levels of HCC tumour markers α-fetoprotein (AFP) and CA199. There was a positive correlation between the expression of SEPC markers and diameter of HCC tumours in differently differentiated specimens (P < 0.01). The expression levels of SEPC markers were significantly higher in patients with poorly differentiated HCC than in patients with moderately and highly differentiated HCC (P < 0.05). CONCLUSIONS: SEPCs are closely associated with HCC progression; therefore, SEPCs may be considered potential prognostic and metastatic biomarkers and therapeutic candidates for HCC.

A proposed modification for the Barcelona Clinic Liver Cancer staging system: Adding bile duct tumor thrombus status in patients with hepatocellular carcinoma.

BACKGROUND: The Barcelona Clinic Liver Cancer (BCLC) staging system is widely applied to stage hepatocellular carcinoma (HCC). However, it may be inaccurate when applied to East Asian HCC patients. In this study, a large Chinese HCC cohort was analyzed to evaluate possible modifications for the BCLC staging system. METHODS: Between January 1995 and December 2009, 622 HCC patients who underwent hepatectomy were enrolled. Prognostic risk factors were analyzed using univariate and multivariate analyses. The ability of the modified system to predict survival was evaluated by determining the area under the receiver operating characteristic curve. RESULTS: Patients without bile duct tumor thrombus (BDTT; 1-, 3- and 5-year overall survival, 80%, 60% and 48%, respectively) showed a substantial survival advantage over those with BDTT (1-, 3- and 5-year overall survival, 77%, 42% and 23%, respectively; χ2 = 6.280, P = 0.012). In BCLC stage 0-A patients, significant differences were identified between the BDTT group and the non-BDTT group, while no such differences were found in BCLC stage B patients. Based on this finding, BCLC stage 0-A BDTT patients were recategorized into stage B. The modified BCLC classification featured better performance in the prediction of overall survival than the original system (modified BCLC χ2 = 53.596, P < 0.001; original BCLC χ2 = 46.335, P < 0.001). The ability to predict mortality was also slightly higher using the modified BCLC system. CONCLUSIONS: Modification of the BCLC system to include BDTT status might further enhance its prognostic ability.

[Comparative study of Modified Xiaoyao Pill combining amitriptyline on therapeutic effect and compliance in treating patients with depression].

OBJECTIVE: To comparatively observe the curative effect, adverse reaction and compliance of Modified Xiaoyao Pill combining amitriptyline (MXP-At) in treating patients with depression. METHODS: Sixty-four patients with diagnosis of depression matched to the Chinese Classification of Mental Disorders (CCMD-3) were randomly assigned to 2 groups, the treatment group treated with MXP-At and the control group with fluoxeline, 32 cases in each group. The curative effect was evaluated by Hamilton depression (HAMD) scale and the adverse reaction was recorded before treatment and at the 2nd, 4th and 12th week of the treatment. Patients were regularly followed up from the 12th week to the 24 th week. The curative effect and compliance in the two groups were compared. RESULTS: The HAMD score dropped in both groups from the 2nd week of the treatment, and at that time, it was lower in the control group than that in the treatment group (P < 0.05); but at the 4th week, no significant difference was found in the therapeutic effect and the HAMD score between the two groups. However, 3 and 14 cases in the treatment and the control group were relapsed during the 12 weeks of follow-up respectively. CONCLUSION: MXP-At shows a curative effect similar to fluoxetine on depression but with less adverse reaction, and is not expensive.

[Prophylaxis and management of ischemic-type biliary lesion after orthotopic liver transplantation].

OBJECTIVE: To investigate the cause, prophylaxis, and management of ischemic-type biliary lesion (ITBL) after orthotopic liver transplantation. METHODS: The clinical data of 212 operations of orthotopic liver transplantation on 209 patients, 184 males and 25 females, aged 44.5 (18-69), including 3 patients undergoing secondary liver transplantation, between February 1999 and August 2004 were reviewed retrospectively. RESULTS: ITBL occurred in 14 patients (6.6%), among whom 5 had biliary lesions of hepatic bifurcation, 3 had intrahepatic biliary lesions, and 6 had multiple extrahepatic and intrahepatic biliary lesions. The incidence rate of ITBL among the recipients of liver in cold storage for more than 10 hours, with donor-recipient ABO blood type incompatibility, with postoperative hepatic arterial lesions, and with hepatitis B related hepatic failure as the primary disease were 9.8% (10/102), 22.2% (2/9), 40% (2/5), and 14.6% (7/48) respectively. The 14 patients with ITBL were managed with conservative treatment, endoscopy, Roux-en-Y anastomosis, or re-transplantation. Seven of the 14 patients were cured, the condition of 5 patients was improved, and 1 patient died with a mortality of 7.1% (1/14). The incidence of ITBL-related graft loss was 23% (3/14). CONCLUSION: It is crucial to avoid too long preservation time of donor liver and donor-recipient ABO blood type incompatibility, and timely management of postoperative hepatic arterial lesions so as to prevent ITBL. Proper treatment for ITBL should be chosen according to the specific conditions of the lesion of biliary duct tree.

[Liver transplantation for treating hepatocellular carcinoma].

OBJECTIVE: To evaluate the role of orthotopic liver transplantation (OLT) in treating hepatocellular carcinoma (HCC). METHODS: Data of 92 consecutive orthotopic liver transplantations (OLTs) performed during January 1999 and February 2005 at our institution were analyzed. RESULTS: Of the 92 recipients, 8 HCC patients were stage I, 13 were stage II, 12 stage III and 59 stage IV (UICC TNM staging system). Overall 1-, 2-, 3-, 5-year patient survival rates were 65.3%, 27.0%, 20.0%, and 6.9%, respectively. When OLT indications were considered, best recipients survival was obtained in stage I patients (100.0%, 100.0%, 66.7%, and 50.0% at 1, 2, 3, and 5 years, respectively) and stage II patients (85.7%, 66.7%, and 66.7% at 1, 2 and 3 years, respectively). Whereas, 1, 2, 3 and 5-year recipients survival rates were 50.0%, 0, 0, 0 in stage III patients, and 58.1%, 20.0%, 13.0% and 5.0% in stage IV patients. CONCLUSIONS: The prognosis of different stages of HCC patients who underwent OLT was significantly different. The OLT recipients with HCC should be strictly selected. Long-term recipient survival could be obtained in stage I and stage II patients.

[Cyclosporine microemulsion C2 monitoring in Chinese adult liver transplant recipients: a preliminary randomized control trial].

OBJECTIVE: To evaluate the safety and reliability of cyclosporine microemulsion (CsA-ME) C(2) monitoring and to determine the target level of C(2) in Chinese adult liver transplant recipients. METHODS: 53 Chinese adult liver transplant recipients were randomly divided into three groups (group C(0), n = 17; group high level C(2), n = 18; group low level C(2), n = 18). Blood chemistry reflecting heart, liver and renal function and CsA level were examined at certain interval during follow-up. The change of immune status and episodes of rejection were also observed closely. RESULTS: The group low level C(2) had the lowest CsA oral dose (2.51 +/- 0.37 mg/kg/d), and had significant difference compared with the other groups (P < 0.01). The best liver, heart and renal function was observed in group low level C(2). The CD(4)(+)/CD(8)(+) ratio of group low level C(2) was 1.04 +/- 0.68, which had no significant difference with C(0) group. The rejection incidence of the three groups had no significant difference. group low level C(2) had highest clinical benefit ratio (72.22%), while the clinical benefit of group high level C(2) is the lowest (11.11%). CONCLUSIONS: With rational target level, C(2) monitoring can show us the proper oral dose of CsA which can decrease the side effects remarkably without rejection episodes increasing. The target level of C(2) in Chinese adult liver transplant recipients might be: 600-800 ng/ml 1 to 6 months posttransplant, 400-600 ng/ml 7-12 months posttransplant.

Outcomes of liver transplantation for end-stage biliary disease: A comparative study with end-stage liver disease.

AIM: To evaluate the outcomes of patients with end-stage biliary disease (ESBD) who underwent liver transplantation, to define the concept of ESBD, the criteria for patient selection and the optimal operation for decision-making. METHODS: Between June 2002 and June 2014, 43 patients with ESBD from two Chinese organ transplantation centres were evaluated for liver transplantation. The causes of liver disease were primary biliary cirrhosis (n = 8), cholelithiasis (n = 8), congenital biliary atresia (n = 2), graft-related cholangiopathy (n = 18), Caroli's disease (n = 2), iatrogenic bile duct injury (n = 2), primary sclerosing cholangitis (n = 1), intrahepatic bile duct paucity (n = 1) and Alagille's syndrome (n = 1). The patients with ESBD were compared with an end-stage liver disease (ESLD) case control group during the same period, and the potential prognostic values of multiple demographic and clinical variables were assessed. The examined variables included recipient age, sex, pre-transplant clinical status, pre-transplant laboratory values, operation condition and postoperative complications, as well as patient and allograft survival rates. Survival analysis was performed using Kaplan-Meier curves, and the rates were compared using log-rank tests. All variables identified by univariate analysis with P values < 0.100 were subjected to multivariate analysis. A Cox proportional hazard regression model was used to determine the effect of the study variables on outcomes in the study group. RESULTS: Patients in the ESBD group had lower model for end-stage liver disease (MELD)/paediatric end-stage liver disease (PELD) scores and a higher frequency of previous abdominal surgery compared to patients in the ESLD group (19.2 ± 6.6 vs 22.0 ± 6.5, P = 0.023 and 1.8 ± 1.3 vs 0.1 ± 0.2, P = 0.000). Moreover, the operation time and the time spent in intensive care were significantly higher in the ESBD group than in the ESLD group (527.4 ± 98.8 vs 443.0 ± 101.0, P = 0.000, and 12.74 ± 6.6 vs 10.0 ± 7.5, P = 0.000). The patient survival rate in the ESBD group was not significantly different from that of the ESBD group at 1, 3 and 5 years (ESBD: 90.7%, 88.4%, 79.4% vs ESLD: 84.9%, 80.92%, 79.0%, χ(2) = 0.194, P = 0.660). The graft-survival rates were also similar between the two groups at 1, 3 and 5 years (ESBD: 90.7%, 85.2%, 72.7% vs ESLD: 84.9%, 81.0%, 77.5%, χ(2) = 0.003, P = 0.958). Univariate analysis identified MELD/PELD score (HR = 1.213, 95%CI: 1.081-1.362, P = 0.001) and bleeding volume (HR = 0.103, 95%CI: 0.020-0.538, P = 0.007) as significant factors affecting the outcomes of patients in the ESBD group. However, multivariate analysis revealed that MELD/PELD score (HR = 1.132, 95%CI: 1.005-1.275, P = 0.041) was the only negative factor that was associated with short survival time. CONCLUSION: MELD/PELD criteria do not adequately measure the clinical characteristics and staging of ESBD. The allocation system based on MELD/PELD criteria should be re-evaluated for patients with ESBD.

[Prevention and management of biliary complications following orthotopic liver transplantation].

OBJECTIVE: To prevent and manage biliary complications after orthotopic liver transplantation (OLT). METHODS: Ninety-five patients of OLT performed at our institute from February, 1999 to December 2002 were retrospectively analysed. Recipient operation was performed using standard method combined with veno-venous bypass in 12 patients and piggyback method in 78 patients and living-related liver transplantation in 5 patients. Biliary reconstruction was performed by end-to-end choledochocholedochostomy (C-C) over a T-tube in 55 patients and without a T-tube in 36 patients while the remaining 4 patients underwent Roux-en-Y choledochojejunostomy (CRY). C-C and CRY were performed by the interrupted or continuous suture with 5 - 0 or 6 - 0 Vicryl or PDS. Routine examination of liver function, Doppler ultrasonography and cholangiography were performed during the follow-up period. RESULTS: Biliary complications occurred in 7 patients (7.3%). Two patients with bile leakage at the anastomotic site developed biliary peritonitis on the seventh and tenth postoperative day and needed reoperation. One patient developed anastomotic biliary stricture one month after the operation and was cured by endoscopic stenting. Two patients developed bile leakage after T-tube removal. One of the two patients was treated conservatively and the other underwent a exploratory laparotomy to ligate the T-tube tract and drain the peritoneal cavity. One patient died of biliary vast syndrome five months after OLT and one patient died of biliary tract necrosis secondary to hepatic artery thrombosis on the tenth postoperative day. One - 42-month (mean 11.4 months) follow-up revealed no biliary stricture in 74 patients. No biliary stone and biliary sludge were detected by Doppler ultrasound and/or cholangiography. Serological examinations proved that liver grafts functioned well in these patients. CONCLUSIONS: To prevent biliary complications, it is crucial to protect biliary mucosa and arterial blood supply of the common bile duct while harvesting the graft and to obtain perfect mucosa-to-mucosa apposition of no-tension end-to-end anastomosis of the bile duct. Endoscopic dilation and stenting are effective for post-OLT extrahepatic biliary stricture.

Increased liver-infiltrating CD8+FoxP3+ regulatory T cells are associated with tumor stage in hepatocellular carcinoma patients.

Hepatocellular carcinoma (HCC) is the most common primary malignant tumor of the liver, and patients who are diagnosed with this tumor typically have a poor prognosis. The suppressive effects of CD4(+)FoxP3(+) regulatory T cells on antitumor immune response in HCC have been studied in great detail. CD8(+)FoxP3(+) regulatory T cells have recently been detected in tumors; however, the role of CD8(+)FoxP3(+) regulatory T cells in HCC is still unknown. Here, the frequency and phenotype of CD8(+)FoxP3(+) regulatory T cells were analyzed by multicolor flow cytometry in liver of HCC patients and healthy donors. We observed that the percentage of these cells in HCC patients was significantly higher than that observed in healthy control donors (p = 0.0155); their phenotype was close to that of CD4(+) regulatory T cells. Furthermore, we show that CD8(+)FoxP3(+) regulatory T cells are activated and act as effector memory cells (EM, CD45RA(-)CCR7(-)CD27(+/-)CD28(+)). Most importantly, a higher percentage of intrahepatic CD8(+)FoxP3(+) regulatory T cells was found in patients with advanced HCC than in those with early HCC in terms of tumor-node-metastasis (TNM) stage (stage I vs III, p = 0.0007). These data suggest that CD8(+)FoxP3(+) regulatory T cells may contribute to HCC immune escape and disease progression.