Characteristics of early gastric tumors with different differentiation and predictors of long-term outcomes after endoscopic submucosal dissection.

BACKGROUND: Gastric cancer is a common malignant tumor of the digestive tract, and endoscopic submucosal dissection (ESD) is the preferred treatment for early-stage gastric cancer. The analysis of the epidemiological characteristics of gastric mucosal tumors with different differentiation degrees and the influencing factors of long-term ESD efficacy may have certain significance for revealing the development of gastric cancer and ESD. AIM: To analyze the features of gastric mucosal tumors at different differentiation levels, and to explore the prognostic factors of ESD. METHODS: We retrospectively studied 301 lesions in 285 patients at The Second Affiliated Hospital of Xi'an Jiaotong University from 2014 to 2021, according to the latest Japanese guidelines (sixth edition), and divided them into low-grade intraepithelial neoplasia (LGIN), high-grade intraepithelial neoplasia (HGIN), and differentiated and undifferentiated early carcinoma. They are followed up by endoscopy, chest and abdominal computed tomography at 3, 6 and 12 months after ESD. We compared clinicopathologic characteristics, ESD efficacy, and complications with different degrees of differentiation, and analyzed the related factors associated with ESD. RESULTS: HGIN and differentiated carcinoma patients were significantly older compared with LGIN patients (P < 0.001) and accounted for more 0-IIc (P < 0.001), atrophic gastritis was common (P < 0.001), and irregular microvascular patterns (IMVPs) and demarcation lines (DLs) were more obvious (P < 0.001). There was more infiltration in the undifferentiated carcinoma tissue (P < 0.001), more abnormal folds and poorer mucosal peristalsis (P < 0.001), and more obvious IMVPs, irregular microsurface patterns and DLs (P < 0.05) than in the LGIN and HGIN tissues. The disease-free survival rates at 2, 5, and 8 years after ESD were 95.0%, 90.1%, and 86.9%, respectively. Undifferentiated lesions (HR 5.066), white moss (HR 7.187), incomplete resection (HR 3.658), and multiple primary cancers (HR 2.462) were significantly associated with poor prognosis. CONCLUSION: Differentiations of gastric mucosal tumors have different epidemiological and endoscopic characteristics, which are closely related to the safety and efficacy of ESD.

The BRD4-SRPK2-SRSF2 signal modulates the splicing efficiency of ACSL3 pre-mRNA and influences erastin-induced ferroptosis in osteosarcoma cells.

Lipid metabolism is the key to ferroptosis susceptibility. However, little is known about the underlying mechanisms in osteosarcoma cells. Functional restriction of bromodomain-containing protein 4 (BRD4) reduced the susceptibility to erastin-induced ferroptosis of osteosarcoma cells both in vitro and in vivo. Mechanically, BRD4 controls the splicing efficiency of the RNA precursor (pre-mACSL3) of ACSL3 (ACSL3) by recruiting serinerich/threonine protein kinase 2 (SRPK2) to assemble the splicing catalytic platform. Moreover, the AMP-binding domain of ACSL3 significantly influences arachidonic acid synthesis and thus determines the susceptibility to erastin-induced ferroptosis. Overall, we found a BRD4-mediated pre-mACSL3 splicing influences erastin-induced ferroptosis by affecting arachidonic acid synthesis in osteosarcoma cells. Data in this study fills some of the gap in understanding the post-transcriptional regulatory mechanisms of ACSL3 and provides new insights into the mechanisms of lipid metabolism regulation and its effect on susceptibility to ferroptosis in osteosarcoma cells.

Long non-coding RNA PVT1 (PVT1) affects the expression of CCND1 and promotes doxorubicin resistance in osteosarcoma cells.

Background: Acquired drug-resistance is the major risk factor for poor prognosis and short-term survival in patients with osteosarcoma (OS). Accumulating evidence has revealed that long noncoding RNAs (lncRNAs), including plasmacytoma variant translocation 1 (PVT1), play potential regulatory roles in the malignant development of OS. Considering the subcellular distribution of PVT1 as both nuclear and cytoplasmic lncRNA, a thorough exploration of its extensive mechanisms becomes essential. Methods: The GEO database was utilized for the acquisition of gene expression data, which was subsequently analyzed to fulfill the research objectives. The subcellular localization of PVT1 in OS cells was determined using fluorescence in situ hybridization (FISH) and quantitative real-time polymerase chain reaction (qRT-PCR). Additionally, the sensitivity of OS cells to doxorubicin was comprehensively evaluated through measurements of cell viability, site-specific proliferation capacity, and the relative expression abundance of multidrug resistance-related proteins (MRPs). In order to investigate the differential response of OS cells with varying levels of PVT1 expression to doxorubicin, pulmonary metastasis mice models were established for in vivo studies. Molecular interactions were further examined using the dual-luciferase assay and RNA immunoprecipitation assay (RIP) to analyze the binding sites of miR-15a-5p and miR-15b-5p on PVT1 and G1/S-specific cyclinD1 (CCND1) mRNA. Furthermore, the chromatin immunoprecipitation (ChIP) and dual-luciferase assay were employed to assess the transcriptional activation of the proto-oncogene c-myc (MYC) on the CCND1 promoter and identify the corresponding binding sites. Results: In doxorubicin resistant OS cells, transcription levels of PVT1, MYC and CCND1 were significantly higher than those in original cells. In vivo experiments demonstrated that OS cells rich in PVT1 expression exhibited enhanced tumorigenicity and resistance to doxorubicin. In vitro experiments, it has been observed that overexpression of PVT1 in OS cells is accompanied by an upregulation of CCND1, thereby facilitating resistance to doxorubicin. Nonetheless, this PVT1-induced resistance can be effectively attenuated by the knockdown of CCND1. Mechanistically, PVT1 functions as a competitive endogenous RNA (ceRNA) that influences the expression of CCND1 by inhibiting the degradation function of miR-15a-5p and miR-15b-5p on CCND1 mRNA. Additionally, as a neighboring gene of MYC, PVT1 plays a role in maintaining MYC protein stability, which further enhances MYC-dependent CCND1 transcriptional activity. Conclusion: The resistance of OS cells to doxorubicin is facilitated by PVT1, which enhances the expression of CCND1 through a dual mechanism. This findings offer a novel perspective for comprehending the intricate regulatory mechanisms of long non-coding RNA in influencing the expression of coding genes.

Autologous Costal Cartilage Grafting for a Large Osteochondral Lesion of the Femoral Head: A 1-Year Single-Arm Study with 2 Additional Years of Follow-up.

BACKGROUND: There is currently no ideal treatment for osteochondral lesions of the femoral head (OLFH) in young patients. METHODS: We performed a 1-year single-arm study and 2 additional years of follow-up of patients with a large (defined as >3 cm 2 ) OLFH treated with insertion of autologous costal cartilage graft (ACCG) to restore femoral head congruity after lesion debridement. Twenty patients ≤40 years old who had substantial hip pain and/or dysfunction after nonoperative treatment were enrolled at a single center. The primary outcome was the change in Harris hip score (HHS) from baseline to 12 months postoperatively. Secondary outcomes included the EuroQol visual analogue scale (EQ VAS), hip joint space width, subchondral integrity on computed tomography scanning, repair tissue status evaluated with the Magnetic Resonance Observation of Cartilage Repair Tissue (MOCART) score, and evaluation of cartilage biochemistry by delayed gadolinium-enhanced magnetic resonance imaging of cartilage (dGEMRIC) and T2 mapping. RESULTS: All 20 enrolled patients (31.02 ± 7.19 years old, 8 female and 12 male) completed the initial study and the 2 years of additional follow-up. The HHS improved from 61.89 ± 6.47 at baseline to 89.23 ± 2.62 at 12 months and 94.79 ± 2.72 at 36 months. The EQ VAS increased by 17.00 ± 8.77 at 12 months and by 21.70 ± 7.99 at 36 months (p < 0.001 for both). Complete integration of the ACCG with the bone was observed by 12 months in all 20 patients. The median MOCART score was 85 (interquartile range [IQR], 75 to 95) at 12 months and 75 (IQR, 65 to 85) at the last follow-up (range, 24 to 38 months). The ACCG demonstrated magnetic resonance properties very similar to hyaline cartilage; the median ratio between the relaxation times of the ACCG and recipient cartilage was 0.95 (IQR, 0.90 to 0.99) at 12 months and 0.97 (IQR, 0.92 to 1.00) at the last follow-up. CONCLUSIONS: ACCG is a feasible method for improving hip function and quality of life for at least 3 years in young patients who were unsatisfied with nonoperative treatment of an OLFH. Promising long-term outcomes may be possible because of the good integration between the recipient femoral head and the implanted ACCG. LEVEL OF EVIDENCE: Therapeutic Level IV . See Instructions for Authors for a complete description of levels of evidence.

Altered intra- and inter-network brain functional connectivity in upper-limb amputees revealed through independent component analysis.

Although cerebral neuroplasticity following amputation has been observed, little is understood about how network-level functional reorganization occurs in the brain following upper-limb amputation. The objective of this study was to analyze alterations in brain network functional connectivity (FC) in upper-limb amputees (ULAs). This observational study included 40 ULAs and 40 healthy control subjects; all participants underwent resting-state functional magnetic resonance imaging. Changes in intra- and inter-network FC in ULAs were quantified using independent component analysis and brain network FC analysis. We also analyzed the correlation between FC and clinical manifestations, such as pain. We identified 11 independent components using independent component analysis from all subjects. In ULAs, intra-network FC was decreased in the left precuneus (precuneus gyrus) within the dorsal attention network and left precentral (precentral gyrus) within the auditory network; but increased in the left Parietal_Inf (inferior parietal, but supramarginal and angular gyri) within the ventral sensorimotor network, right Cerebelum_Crus2 (crus II of cerebellum) and left Temporal_Mid (middle temporal gyrus) within the ventral attention network, and left Rolandic_Oper (rolandic operculum) within the auditory network. ULAs also showed decreased inter-network FCs between the dorsal sensorimotor network and ventral sensorimotor network, the dorsal sensorimotor network and right frontoparietal network, and the dorsal sensorimotor network and dorsal attention network. Correlation analyses revealed negative correlations between inter-network FC changes and residual limb pain and phantom limb pain scores, but positive correlations between inter-network FC changes and daily activity hours of stump limb. These results show that post-amputation plasticity in ULAs is not restricted to local remapping; rather, it also occurs at a network level across several cortical regions. This observation provides additional insights into the plasticity of brain networks after upper-limb amputation, and could contribute to identification of the mechanisms underlying post-amputation pain.

[Case-control study on carpal canal endoscopy and arthroscopy for the treatment of plantar fasciopathy].

OBJECTIVE: To explore clinical effects of carpal canal endoscopy in treating patients with plantar fasciopathy who failed by conservative treatment. METHODS: From August 2018 to August 2019, 50 patients with plantar fascia were divided into two groups and 25 patients in each group. In carpal canal endoscopy group, included 11 males and 14 females, aged from 39 to 67 years old with an average of(57.7±6.4) years old;carpal canal endoscopy was used to plantar fascia release. In arthroscopy group, included 9 males and 16 females, aged from 41 to 73 years old with an average of (58.1±7.2) years old;conventional 4.0 mm arthroscopy Instruments was used to plantar fascia release. Operation time, hospitalization expense and postoperative complications between two groups were observed and compared. Postoperative visual analogue scale(VAS) and American Orthopedic Foot Ankle Society (AOFAS) score were used to evaluate clinical function. RESULTS: All patients were followed up from 12 to 18 months with an average of (14.3±2.1) months. There were significant differentces in operation time and hospitalization expense between two groups (P<0.05). Surgical incision healed well in carpal canal endoscopy group, and 2 patients delayed union in arthroscopy group, and no difference between two groups (P>0.05). There were no statistical differences in VAS, AOFAS and grading between two groups at 12 months after operation(P>0.05). CONCLUSION: The outcome of carpal canal endoscopy and arthroscopy has similar effects in treating plantar fascia. While carpal canal endoscopy has advantages of need not perfusion during opertaion, protect soft tissue well, less operation time, and lower cost.

A retrospective cohort study on prevalence of postoperative complications in comminuted patellar fractures: comparisons among stabilized with Cannulated-Screw, Kirschner-Wire, or Ring-Pin Tension Bands.

BACKGROUND: Displaced patellar fractures are commonly treated with open reduction and fixation with several different types of tension-band (TB) constructs. The main objective of this study was to compare the prevalence of postoperative complications after surgical stabilization of comminuted patellar fractures with either a modified Kirschner-wire tension band (MKTB), a cannulated-screw tension band (CSTB), or a ring-pin tension band (RPTB). METHODS: We conducted a retrospective and consecutive cohort study of comminuted patellar fractures (n = 334) stabilized using a TB construct. Postoperative premature loss of reduction, infection, and skin breakdown were compared according to the type of TB constructs received (MKTB, CSTB, or RPTB). The rate of implant removal due to symptomatic hardware was also evaluated. RESULTS: Fixation failure rate was significantly different among the groups (P = 0.013), with failure rates of 4.7% observed in the MKTB group,14.5% in the CSTB group, and 4.9% in the RPTB group. Skin breakdown and infection were not significantly different among the groups (Ps > 0.05). Due to symptomatic hardware, 40.5% of the patients in the MKTB group, 22.9% in the CSTB group, and 24.3% in the RPTB group underwent implant removal (P = 0.004). After adjusting for age, gender, comorbidities, number of supplementary screws/K-wires, and use of cerclage cables, multivariate regression analysis revealed that CSTB contributed to a 2.08-times greater risk of fixation failure compared to RPTB, while MKTB and RPTB were similar in risk of failure. In addition, it was found that patients who underwent MKTB fixation were more than twice as likely to undergo implant removal for symptomatic hardware compared with RPTB (odds ratio = 2.11, 95% CI = 1.20 to 3.72; P = 0.010). CONCLUSIONS: RPTB have advantage over MKTB and CSTB fixation in terms of symptomatic hardware and premature failure, respectively. LEVEL OF EVIDENCE: Therapeutic Level III.

SET7 interacts with HDAC6 and suppresses the development of colon cancer through inactivation of HDAC6.

SET7 is the first lysine methyltransferase and plays vital roles in tumorigenesis. This study aims to seek clinical value of SET7 in colorectal cancer (CRC) patients, along with its biological impact on cell proliferation and migration. In patients with CRC, the expression of SET7 in cancer tissue was significantly lower than that in adjacent tissue, and down-regulated SET7 was closely correlated with poor prognosis. Loss-of-function and gain-of-function studies indicated that SET7 inhibited cell proliferation and migration by acting on HDAC6 substrate in colon cancer cells. Besides, the co-immunoprecipitation assay showed that SET7 and HDAC6 can interact reciprocally. The interaction effect between SET7 and HDAC6 could significantly reduce cell viability, scratch healing rate, and migrated cells in colon cancer cells. Instead of acting on each endogenous expression, the results demonstrated that the level of acetylated α-tubulin was greatly decreased in HDAC6 overexpression group, while significantly increased in SET7 overexpressed group. However, changes were partly restored in both SET7 and HDAC6-transfected group. On the contrary, the expression of acetylated α-tubulin protein was significantly increased in HDAC6 knockdown group, but higher in both HDAC6 and SET7 silencing group. These results indicated that SET7 played a role in tumor suppression via increasing levels of acetylated-α-tubulin mediated by HDAC6. In addition, the interaction effect significantly decreased the ratios of p-ERK/ERK, which indicated that it may partly suppress ERK signaling pathway. In conclusion, SET7 is a promising therapeutic target for preventing metastasis and improving prognosis in colon cancer.

The effect of Salvia miltiorrhiza in a mouse model of hepatic sinusoidal obstruction syndrome induced by Gynura segetum

Background and aims: to investigate the potential effect and mechanism of Salvia miltiorrhiza in Gynura segetum-induced hepatic sinusoidal obstruction syndrome (HSOS). Methods: the mice were gavaged with PBS, Gynura segetum or Gynura segetum, along with 100 or 200 mg/kg Salvia miltiorrhiza. Histological scoring and liver function were performed. The expression of tumor necrosis factor-alpha (TNF-alfa), vascular cellular adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1) and nuclear transcription factor P65 (NF-κBp65) were determined by reverse transcriptase polymerase chain reaction (RT-PCR) and western blot. Results: liver function were effectively improved in the Salvia miltiorrhiza groups. The levels of TNF-alfa, VCAM-1, ICAM-1 and NF-κBp65 were significantly lower in the Salvia miltiorrhiza groups than in the Gynura segetum group. Conclusions: Salvia miltiorrhiza has a therapeutic effect on Gynura segetum-induced HSOS

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The effect of Salvia miltiorrhiza in a mouse model of hepatic sinusoidal obstruction syndrome induced by Gynura segetum.

BACKGROUND AND AIMS: to investigate the potential effect and mechanism of Salvia miltiorrhiza in Gynura segetum-induced hepatic sinusoidal obstruction syndrome (HSOS). METHODS: the mice were gavaged with PBS, Gynura segetum or Gynura segetum, along with 100 or 200 mg/kg Salvia miltiorrhiza. Histological scoring and liver function were performed. The expression of tumor necrosis factor-alpha (TNF-α), vascular cellular adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1) and nuclear transcription factor P65 (NF-κBp65) were determined by reverse transcriptase polymerase chain reaction (RT-PCR) and western blot. RESULTS: liver function were effectively improved in the Salvia miltiorrhiza groups. The levels of TNF-α, VCAM-1, ICAM-1 and NF-κBp65 were significantly lower in the Salvia miltiorrhiza groups than in the Gynura segetum group. CONCLUSIONS: Salvia miltiorrhiza has a therapeutic effect on Gynura segetum-induced HSOS.

Histone deacetylase 6 is overexpressed and promotes tumor growth of colon cancer through regulation of the MAPK/ERK signal pathway.

Purpose: To investigate the expression of histone deacetylase 6 (HDAC6) in colon cancer and its role in colon cancer cell growth and migration. Materials and methods: We detected the expression of HDAC6 in a colon cancer tissue chip using immunochemical staining, and analyzed the difference in HDAC6 expression between cancer and adjacent noncancerous tissues. Then, we explored the relationship between HDAC6 expression and patients' clinicopathological characteristics and prognoses. In adidition, the role of HDAC6 in colon cancer cell growth and migration, as well as its potential related signal pathway, through HDAC6 knockdown was explored. Results: The immunochemical score of HDAC6 expression was higher in cancer tissue than in the adjacent noncancerous tissue (4.54 vs 3.08, P<0.005); similarly, as well as the rate of high HDAC6 expression was higher in cancer tissue than in the adjacent noncancerous tissue (71.1% vs 40.9%, P<0.001). Patients showing high HDAC6 expression had a shorter overall survival time. Additionally, Cox regression analysis showed that high HDAC6 expression was an independent risk factor for poor prognosis. HDAC6 knockdown decreased cell viability, colony formation, and number of migrated colon cancer cells (HCT116 and HT29); the expression of p-MEK, p-ERK, and p-AKT was also decreased, but had no influence on MEK, ERK, and AKT expression. Conclusion: HDAC6 is highly expressed in colon cancer and associated with a poor prognosis. HDAC6 knockdown inhibits colon cancer cell growth and migration, partly through the MAPK/ERK pathway.

Brain remodeling after chronic median nerve compression in a rat model.

Carpal tunnel syndrome is the most common compressive neuropathy, presenting with sensorimotor dysfunction. In carpal tunnel syndrome patients, irregular afferent signals on functional magnetic resonance imaging are associated with changes in neural plasticity during peripheral nerve injury. However, it is difficult to obtain multi-point neuroimaging data of the brain in the clinic. In the present study, a rat model of median nerve compression was established by median nerve ligation, i.e., carpal tunnel syndrome model. Sensory cortex remodeling was determined by functional magnetic resonance imaging between normal rats and carpal tunnel syndrome models at 2 weeks and 2 months after operation. Stimulation of bilateral paws by electricity for 30 seconds, alternating with 30 seconds of rest period (repeatedly 3 times), resulted in activation of the contralateral sensorimotor cortex in normal rats. When carpal tunnel syndrome rats received this stimulation, the contralateral cerebral hemisphere was markedly activated at 2 weeks after operation, including the primary motor cortex, cerebellum, and thalamus. Moreover, this activation was not visible at 2 months after operation. These findings suggest that significant remodeling of the cerebral cortex appears at 2 weeks and 2 months after median nerve compression.

Full-thickness myotomy is associated with higher rate of postoperative gastroesophageal reflux disease.

AIM: To compare long-term occurrence of gastroesophageal reflux disease (GERD) between two different types of peroral endoscopic myotomy (POEM) for achalasia. METHODS: We included all patients with achalasia who underwent POEM at our hospital from August 2011 to October 2012 and had complete GERD evaluation with ≥ 3 years of follow-up. They were divided into circular or full-thickness myotomy groups according to the depth of myotomy. Demographics, Eckardt score, manometry results, 24-h pH monitoring, and GERD symptoms were recorded and compared between the two groups. RESULTS: We studied 56 patients (32 circular myotomy and 24 full-thickness myotomy) with complete GERD evaluation. There was no significant difference between the two groups in terms of treatment success (defined as Eckardt score ≤ 3), postoperative Eckardt score, mean basal lower esophageal sphincter pressure, and 4-s integrated relaxation pressure (4sIRP). Postoperative abnormal esophageal acid exposure was found in 25 patients (44.6%). A total of 13 patients (23.2%) had GERD symptoms and 12 had esophagitis (21.4%). Clinically relevant GERD (abnormal esophageal acid exposure associated with GERD symptoms and/or esophagitis) was diagnosed in 13 patients (23.2%). Multivariate analysis revealed that full-thickness myotomy and low level of postoperative 4sIRP were predictive factors for clinically relevant GERD. CONCLUSION: Efficacy and manometry are comparable between achalasia patients treated with circular or full-thickness myotomy. But patients with full-thickness myotomy and low postoperative 4sIRP have more GERD.

Decreased extracellular pH inhibits osteogenesis through proton-sensing GPR4-mediated suppression of yes-associated protein.

The pH of extracellular fluids is a basic property of the tissue microenvironment and is normally maintained at 7.40 ± 0.05 in humans. Many pathological circumstances, such as ischemia, inflammation, and tumorigenesis, result in the reduction of extracellular pH in the affected tissues. In this study, we reported that the osteogenic differentiation of BMSCs was significantly inhibited by decreases in the extracellular pH. Moreover, we demonstrated that proton-sensing GPR4 signaling mediated the proton-induced inhibitory effects on the osteogenesis of BMSCs. Additionally, we found that YAP was the downstream effector of GPR4 signaling. Our findings revealed that the extracellular pH modulates the osteogenic responses of BMSCs by regulating the proton-sensing GPR4-YAP pathway.

Upregulation of arginase activity contributes to intracellular ROS production induced by high glucose in H9c2 cells.

Arginase is upregulated in some tissues under diabetes states. Arginase can compete with nitroxide synthase (NOS) for the common substrate L-arginine and thus increases oxidative stress by NOS uncoupling. We want to analyze whether arginase is upregulated and contribute to oxidative stress in H9c2 cells during high glucose treatment. H9c2 cells were cultured in normal or high glucose DMEM. Arginase activity increased in parallel with increased cell death and oxidative stress. Arginase inhibitor N ω-hydroxy-nor-l-arginine (nor-NOHA) and NOS inhibitor N ω-nitro-l-arginine methyl ester (L-NAME) could reverse these effects. Despite of upregulated NOS activity, NO production was impaired which could be preserved by nor-NOHA, suggesting a decreased substrate availability of NOS due to increased arginase activity. L-arginine supplementation decreased superoxide production while it could not protect cells from death. Upregulated arginase activity in H9c2 treated with high glucose can cause NOS uncoupling and subsequently reactive oxygen species augmentation and cell death. These findings suggest that arginase will be a novel therapeutic target for treatment of diabetic cardiomyopathy.

A meta-analysis of single-stage versus two-stage management for concomitant gallstones and common bile duct stones.

OBJECTIVE: To conduct a randomized controlled trial (RCT) meta-analysis to evaluate the safety and effectiveness of single-stage [laparoscopic cholecystectomy (LC)+laparoscopic common bile duct exploration (LCBDE)] vs. two-stage management [preoperative endoscopic retrograde cholangiopancreatography (ERCP)+LC] for concomitant gallstones and common bile duct stones. METHODS: RCTs that met the inclusion criteria for data extraction were identified from electronic databases (PubMed, Embase, Science Citation Index, and the Cochrane Library) up to August 2014. The relevant congressional proceedings were also searched. The primary outcomes were stone clearance from the common bile duct, postoperative morbidity and mortality. The secondary outcomes were conversion to other procedures, length of hospital stay, total operative time, and hospitalization charges. The outcomes were calculated as odds ratios (ORs) with 95% confidence intervals (CIs) using RevMan 5.2. RESULTS: Eight RCTs, which included 1130 patients, were identified for analysis in our study. The meta-analysis revealed that the common bile duct stone clearance rate in the single-stage group was higher (OR=1.56, 95% CI: 1.05 to 2.33, P=0.03). The lengths of hospital stay (MD=-1.02, 95% CI: -1.99 to -0.04, P=0.04) and total operative times (MD=-16.78, 95% CI: -27.55 to -6.01, P=0.002) were also shorter in the single-stage group. There was no statistically significant difference between the two groups regarding postoperative morbidity (OR=1.12, 95% CI: 0.79 to 1.59, P=0.52), mortality (OR=0.29, 95% CI: 0.06 to 1.41, P=0.13) and conversion to other procedures (OR=0.82, 95% CI: 0.37 to 1.82, P=0.62). CONCLUSION: Single- and two-stage management for cholecysto-choledocholithiasis had similar mortality and complication rates; however, the single-stage strategy was better in terms of stone clearance, hospital stay and total operative time.

Laparoscopic versus open surgery in children with choledochal cysts: a meta-analysis.

OBJECTIVE: To compare the safety and efficacy between laparoscopic and open cyst excision with hepaticojejunostomy for children with choledochal cysts using meta-analysis. METHODS: Studies comparing the laparoscopic and the open choledochal cyst excision that met the inclusion criteria for data extraction were identified from electronic databases (PubMed, Embase, Science Citation Index, and the Cochrane Library) up to November 2014. The proceedings of relevant congress were also searched. The outcomes were operative time, intraoperative blood loss, time to food intake, postoperative morbidity and mortality, length of hospital stay. Outcomes were calculated as odds ratios (ORs) with 95% confidence intervals (CIs) using RevMan 5.2. RESULTS: Seven retrospective studies were finally included, involving a total of 1016 patients, of whom, 408 cases underwent laparoscopic cyst excision and Roux-en-Y hepaticojejunostomy (LH) and 608 cases underwent open cyst excision and Roux-en-Y hepaticojejunostomy (OH). In LH group compared with OH group, the operative time was longer (MD = 59.11, 95% CI 27.61-90.61, P = 0.0002), while the length of postoperative hospital stay was less (MD = -2.01, 95% CI -2.49 to -1.54, P < 0.00001), the intraoperative blood loss was lower (MD = -37.14, 95% CI -66.69 to -7.60, P = 0.01) and time to food intake was less (MD = -1.14, 95% CI -1.61 to -0.67, P = 0.01). The rate of postoperative morbidity was more in the OH group, but there is no statistically significant difference between the two groups in postoperative morbidity (OR = 0.52, 95% CI 0.13-2.06, P = 0.35). CONCLUSION: Laparoscopic surgery is a feasible, safe treatment of choledochal cyst with less postoperative morbidity, a shorter length of stay and a lower blood loss when compared with open approach. With the improvement of laparoscopic techniques and deftness of surgeons practice, laparoscopic surgery may become the first choice procedure for choledochal cyst.

Pretreatment of mesenchymal stem cells with angiotensin II enhances paracrine effects, angiogenesis, gap junction formation and therapeutic efficacy for myocardial infarction.

BACKGROUND: Pretreatment of mesenchymal stem cells (MSCs) with growth factors is reported to be an effective route for improving cell-based therapy of myocardial infarction (MI). Angiotensin II (Ang II) triggers vascular endothelial growth factor (VEGF) synthesis in MSCs. This study aimed to investigate the effects and mechanisms of Ang II pretreatment in enhancing the therapeutic efficacy of MSCs in MI. METHODS: MSCs and endothelial cells (ECs) were isolated from Sprague-Dawley rats. After pretreated with or without 100 nM of Ang II for 24 h, the MSCs were directly injected into the border zones of the ischemic heart. Cardiac function, fibrosis, infarct size, VEGF expression, angiogenesis, and cell differentiation in the infarcted myocardium were determined after 30 days. The cell apoptosis of MSCs post hypoxia was assessed using flow cytometry. The angiogenic activity of MSCs was analyzed using tube formation assay. The gap junction protein connexin-43 (Cx43) expression was detected. RESULTS: Compared with the MSC group, pretreatment of MSCs with Ang II resulted in better cardiac function, less cardiac fibrosis, smaller infarct size, and higher expression of VEGF and Von Willebrand Factor in ischemic myocardium, but no promotion of cardiomyocyte-like differentiation of MSCs. Ang II pretreatment enhanced the survival of MSCs and the H9c2 cells surrounding MSCs, and augmented the tube formation of ECs and MSCs. Ang II pretreatment up-regulated the Cx43 expression. CONCLUSIONS: The pretreatment of MSCs with Ang II improved the outcome of MSC-based therapy for MI via the mechanisms of enhancing the paracrine production of VEGF, angiogenesis, and gap junction formation.

Endoscopic treatment of difficult extrahepatic bile duct stones, EPBD or EST: An anatomic view.

Large bile duct stone (> 10 mm) or multiple stones (≥ 3) are challenging for endoscopists. Endoscopic sphincterotomy (EST) is a routine therapeutic endoscopic retrograde cholangiopancreatography (ERCP) procedure usually used. It is safe and effective, but severe perforation or massive bleeding are the main causes of mortality. Because of the permanent destroy of Oddi sphincter, the use of EST is still controversial. Endoscopic papillary balloon dilation (EPBD) gives another way to open the sphincter. Less incidence of bleeding, perforation and partly preserving the Oddi sphincter's function are the main advantages. But high incidence of post-ERCP pancreatitis becomes a predominant problem. According to the anatomical feature of Oddi sphincter, limited EST + EPBD seems a more reasonable procedure. Compared to the former two procedures, it makes the stone extraction process much easier with lower incidences of short-term and long-term complications.

Activation of the AT1R/HIF-1 α /ACE axis mediates angiotensin II-induced VEGF synthesis in mesenchymal stem cells.

A local renin-angiotensin system (RAS) is expressed in mesenchymal stem cells (MSCs) and regulates stem cell function. The local RAS influences the survival and tissue repairing ability of transplanted stem cells. We have previously reported that angiotensin II (Ang II) pretreatment can significantly increase vascular endothelial growth factor (VEGF) synthesis in MSCs through the ERK1/2 and Akt pathways via the Ang II receptor type 1 (AT1R). However, the role of angiotensin-converting enzyme (ACE) has not been clarified. Furthermore, whether Ang II pretreatment activates hypoxia-inducible factor-1α (HIF-1α) in MSCs has not been elucidated. Our data show that both ACE and HIF-1α are involved in promoting VEGF expression in MSCs, and that both are upregulated by Ang II stimulation. The upregulation of ACE appeared after the rapid degradation of exogenous Ang II, and led to the formation of endogenous Ang II. On the other hand, the ACE inhibitor, captopril, attenuated Ang II-enhanced HIF-1α upregulation, while HIF-1α suppression markedly attenuated ACE expression. This interesting finding suggests an interaction between ACE and HIF-1α. We conclude that Ang II pretreatment, as a trigger, activated the AT1R/HIF-1α/ACE axis that then mediated Ang II-induced VEGF synthesis in MSCs.