Manual therapy combined with posterior percutaneous endoscopic cervical decompression for the treatment of cervical spondylotic radiculopathy / 中国骨伤

OBJECTIVE@#To explore the clinical efficacy and safety of manual therapy combined with posterior percutaneous endoscopic cervical decompression(PECD) in the treatment of intractable cervical spondylotic radiculopathy.@*METHODS@#From May 2016 to May 2018, 23 CSR patients who responded poorly to conservative treatment for at least 6 weeks underwent the combination management. Firstly, the patients received the posterior percutaneous endoscopic cervical decompression routine care for the following 4 weeks and manual therapy for another 4 weeks. A total of 23 patients were followed up, including 14 males and 9 females, the age ranged from 29 to 78 years old with an average of (50.30±12.28) years, the course of disease was 3 to 24 months with an average of (9.74±5.76) months. The lesion segment involved C4,5 in 4 cases, C5,6 in 13 cases, C6,7 in 6 cases. The visual analogue scale (VAS), neck disability index (NDI), changes of cervical physiological curvature and interbody stability, adverse events were observed before and after operation. The follow-up time points were before operation, 1 day after operation and 1, 3 and 6 months after operation.@*RESULTS@#All patients successfully completed the operation and manual treatment for 4 to 8 times. Among the 29 cases, 23 patients were followed up for more than 6 months. There was no spinal cord and nerve root injury during the treatment and follow-up. Operation time was from 80 to 120 min with a median of 90 min;intraoperative blood loss was from 35 to 80 ml with a median of 50 ml. NDI, VAS of neck, shoulder and arm each period after operation were significantly lower than those before PECD(P<0.05), while there were no significant improvement in cervical physiological curvature and target segment intervertebral space height(P>0.05);there was no significant change in interbody stability (P>0.05). After received the manual therapy, NDI significantly decreased (P<0.05), however, there was no significant difference in VAS of neck, shoulder and arm, physiological curvature of cervical spine and intervertebral space height of target segment compared with that before manual treatment (P>0.05);there was no significant change in interbody stability (P>0.05).@*CONCLUSION@#Manual therapy combined with PECD in the treatment of intractable cervical spondylotic radiculopathy can not only quickly improve the symptoms, but also alleviate the residual symptoms after PECD safely and effectively, and can not cause obvious signs of accelerated instability of cervical adjacent segments in the short term.

Research on community promotion and application of single acupoint electroacupuncture therapy for lumbar intervertebral disc herniation / 中国针灸

OBJECTIVE@#To observe the clinical effect of single acupoint [Yaotu (extra)] electroacupuncture (EA) therapy on lumbar intervertebral disc herniation (LIDH) and its promotion and application in community medical institutions.@*METHODS@#This research adopted a three-level promotion model, and used multi-center collaboration topics as a platform. A total of 240 patients with LIDH were divided into a group A (top three hospital, 80 cases, 3 cases dropped off), a group B (secondary hospital, 80 cases, 8 cases dropped off), and a group C (community health center, 80 cases, 7 cases dropped off). All groups were treated with EA at a single acupoint [Yaotu (extra)] under the guidance of a unified experimental protocol. The EA was given 60 min each time and performed 3 times a week for a total of 2 weeks. The changes of visual analogue scale (VAS) scores of three groups before and after each treatment were compared, and the clinical efficacy was evaluated.@*RESULTS@#Compared with before each treatment, the VAS scores of three groups after each treatment decreased (@*CONCLUSION@#The single acupoint EA therapy has a significant effect in the treatment of LIDH, can quickly relieve the pain symptoms, and has the characteristics of simple operation and easy control, suitable for promotion and application in primary hospitals.

Radical modular pancreatoduodenectomy for pancreatic head cancer using a combination of multiple artery-first approaches technique.

The aim of this study was to describe and assess the efficacy of a combination of multiple artery-first approaches (CMAFA) in pancreatoduodenectomy (PD) depending on the tumor location from an embryonic point of view.Between January 2011 and December 2016, seventy-nine consecutive patients with pancreatic head cancer (PHC) underwent PD with curative intent. Patients were classified into two groups according to the surgical procedure: CMAFA-PD group (n = 38) and conventional PD (Co-PD) group (n = 41). Clinicopathlogical variables and clinical outcomes were compared among the two groups.The CMAFA technique demonstrated an improved rate of R0 resection (89.5% vs. 70.7%, P = .038) and a higher median lymph node yield (24 vs.20, P = .034). The CMAFA-PD group was associated with reduced blood loss (450 vs. 600 ml, P = .049), lower rate of blood transfusion (23.7% vs. 46.3%, P = .035), and shorter length of hospital stay (19 vs. 26 days, P < .001). The rates of 90-day mortality, major morbidity, and readmission were comparable among the two groups.This study demonstrates that CMAFA is a feasible and efficient technique with acceptable perioperative and oncological outcomes in treating patients with PHC.

miR-191 Inhibition Induces Apoptosis Through Reactivating Secreted Frizzled-Related Protein-1 in Cholangiocarcinoma.

BACKGROUND/AIMS: Cholangiocarcinoma (CCA) is one of the most common malignant tumors of the biliary tract originating from biliary epithelial cells. Although many therapeutic strategies have been developed to treat CCA, the survival rate for CCA patients is still quite low. Thus it is urgent to elucidate the pathogenesis of CCA and to explore novel therapeutic targets. miR-191 has been shown to be associated with many human solid cancers, but the function of miR-191 in CCA is still poorly understood. METHODS: We first investigated the expression level of miR-191 in human CCA tissues and cell lines with quantitative real-time PCR (qRT-PCR). The effects of miR-191 on CCA cells were determined by Cell Counting Kit-8 assay, colony formation assay and acridine orange/ethidium bromide staining. Finally, we utilized qRT-PCR, western blot and luciferase reporter assays to verify the miR-191 target gene. RESULTS: We showed that miR-191 was up-regulated in CCA cell lines and patients. Knockdown of miR-191 by transfection of its inhibitor sequence blocked RBE cells viability and induced apoptosis of RBE cells. Both qRT-PCR and western blot analysis showed that the secreted frizzled-related protein-1 (sFRP1) level was negatively correlated with that of miR-191. Luciferase assay validated that sFRP1 was a direct target of miR-191. Moreover, knockdown of miR-191 led to suppression of Wnt/ß-catenin signaling activation. Co-transfection of sFRP1 small interfering RNA (siRNA) and miR-191 inhibitor re-activated the Wnt/ß-catenin signaling pathway as detected by an increased level of ß-catenin and phosphorylation of GSK-3ß, and restored the expression of survivin and c-myc in RBE cells. Co-transfection of sFRP1 siRNA with miR-191 inhibitor restored the colony formation ability and viability of RBE cells. CONCLUSION: Taken together, our results demonstrate a novel insight into miR-191 biological function in CCA. Our findings suggest that miR-191 is a potential therapeutic target of CCA treatment.

Results of adjuvant radiation therapy for locoregional perihilar cholangiocarcinoma after curative intent resection.

PURPOSE: This study sought to define the role of adjuvant radiation therapy (RT) for patients with curative intent resection of perihilar cholangiocarcinoma (pCCA). PATIENTS AND METHODS: By using the Surveillance, Epidemiology and End Results (SEER) registry, 1,917 patients with non-metastatic pCCA who underwent surgical resection from 1988 to 2009 were included in this study. Propensity score methods were used to compare the survival outcomes of patients treated with and without adjuvant RT after controlling for selection bias. RESULTS: Of the 1,917 patients, 762 (39.7%) received adjuvant RT. In the unmatched population, median overall survival (OS) for patients receiving adjuvant RT compared with those undergoing surgery alone was 23 versus 22 months (P=0.651). Patients who received adjuvant RT were younger (65 vs 68 years, P<0.001), had more regional diseases (86.0% vs 76.7%, P<0.001), and had more positive lymph nodes (43.8% vs 32.2%, P<0.001). In the matched population, adjuvant RT did not show better OS (22 vs 23 months, P=0.978) or cancer-specific survival (CSS) (17 vs 18 months, P=0.554). CONCLUSION: Adjuvant RT is not associated with improved survival of patients with resected pCCA. These data suggest that adjuvant RT should not be routinely used to treat patients with pCCA outside research trials. Ideally, prospective randomized trials should be performed to verify the conclusion of this study.

Identifying survival-associated ceRNA clusters in cholangiocarcinoma.

Competing endogenous RNAs (ceRNAs) represent a novel layer regulations of long non-coding RNAs (lncRNAs) and genes that play important roles in cancer pathogenesis by binding microRNAs (miRNAs). However, the competition mechanism of ceRNAs in cholangiocarcinoma (CHOL) is not fully understood. In this study, we constructed a dysregulated ceRNA competitive network (CCEN) to globally characterize the competing difference between CHOL and normal tissues. Then, we integrated affinity propagation and Kaplan­Meier (K-M) methods to identify functional clusters associated with survival. A total of 7 key ceRNA clusters were identified. Further functional annotation analyses found that Cluster23 and Cluster32 involved cell based functions, and the loss of ceRNA competitive relations in clusters may contribute to CHOL, by disturbing important biological processes, such as 'Pathway in cancer', MAPK and Neurotrophin signaling pathway. This study provides further insights into understanding the competitive mechanism of ceRNAs in CHOL.

Interleukin­6 induces epithelial­mesenchymal transition in human intrahepatic biliary epithelial cells.

The aim of the present study was to determine the role of interleukin-6 (IL-6) in the epithelial-mesenchymal transition (EMT) of human intrahepatic biliary epithelial cell (HIBEC) lines in vitro. HIBECs were stimulated with IL-6 at concentrations of 0, 10, 20, 50 and 100 µg/l for 24 h. A wound healing and Transwell assay were performed to determine the migratory and invasive capacity of HIBECs, respectively. Following 24 h of incubation, IL-6 at 10 and 20 µg/l significantly increased the number of migrated and invaded cells (P<0.05), while stimulation with 50 and 100 µg/l IL-6 resulted in a further increase of the migratory and invasive capacity compared to that in all other groups (P<0.05). Furthermore, reverse-transcription quantitative polymerase chain reaction and western blot analyses were used to detect the mRNA and protein expression of EMT markers E-cadherin and vimentin in HIBECs. Decreased mRNA levels of E-cadherin accompanied by higher mRNA levels of vimentin were observed in the 10, 20, 50, 100 µg/l IL-6 groups compared to those in the 0 µg/l group (all P<0.05). Furthermore, the protein expression of E-cadherin was decreased, while that of vimentin was increased in the 50 and 100 µg/l IL-6 groups compared to those in the 0, 10 and 20 µg/l IL-6 groups (all P<0.05). The present study therefore indicated that IL-6 promoted the process of EMT in HIBECs as characterized by increased migration and invasion of HIBECs and the typical changes in mRNA and protein expression of the EMT markers E-cadherin and vimentin.

The Roles of MicroRNA-122 Overexpression in Inhibiting Proliferation and Invasion and Stimulating Apoptosis of Human Cholangiocarcinoma Cells.

Our study investigated whether microRNA-122 (miR-122) played important roles in the proliferation, invasion and apoptosis of human cholangiocarcinoma (CC) cells. QBC939 and RBE cells lines were chosen and divided into five groups: miR-122 mimic group, anti-miR-122 group, negative control (NC) group, mock group and blank group. MiR-122 expression was measured by qRT-PCR. Roles of miR-122 in cell proliferation, apoptosis and invasion were investigated using MTT assay, flow cytometer and Transwell invasion assay, respectively. MiR-122 expression was lower in CC tissues and QBC939 cell than that in normal bile duct tissues, HCCC-9810 and RBE cells. In both QBC939 and RBE cells lines, miR-122 expression was higher in miR-122 mimic group than that in NC group, mock group and blank group; opposite results were found in anti-miR-122 group. Cell proliferation and invasion were remarkably inhibited in miR-122 mimic group after 48 h/72 h transfection, while apoptotic cells numbers were much greater in miR-122 mimic group; the opposite results were obtained from anti-miR-122 group (all P < 0.05). MiR-122 expression was significantly weaker in CC tissues, and miR-122 overexpression might play pivotal roles in inhibiting proliferation, stimulating apoptosis and suppressing invasion of CC cells, suggesting a new target for CC diagnosis and treatment.

Impact of pancreatic margin status and lymph node metastases on recurrence after resection for invasive and noninvasive intraductal papillary mucinous neoplasms of the pancreas: a meta-analysis.

BACKGROUND: Accurate information is currently lacking regarding the values of positive margins (M(+)) and lymph node (LN) metastases as independent predictors of postoperative recurrence in invasive and noninvasive intraductal papillary mucinous neoplasms (IPMNs) of the pancreas. METHODS: A comprehensive online literature search identified all types of primary studies that included M(+) and LN metastases as risk factors and defined recurrence as an outcome in patients with IPMNs. Suitable articles were also identified by manually researching references in qualifying articles. A meta-analysis of the result was performed using a random effects model. RESULTS: The recurrence rate in noninvasive IPMNs was 3.72% in patients with negative margin (M(-)) versus 9.56% in those with M(+) (odds ratio, OR = 0.37, 95% confidence interval, 95% CI: 0.17-0.78, p = 0.010). The recurrence rate in invasive M(-) IPMNs in was 33.85% compared to 53.66% in M(+) IPMNs (OR = 0.47, 95% CI: 0.25-0.88, p = 0.020). The recurrence rate in invasive IPMNs with positive LN was 76.92% compared to 30.86% with negative LN; OR = 0.15, 95% CI: 0.06-0.37, p < 0.0001). CONCLUSIONS: M(+) were associated with disease recurrence in all patients with IPMN, and nodal metastases were significantly associated with recurrence in invasive IPMN.

Clinical and biological significance of Cdk10 in hepatocellular carcinoma.

Cyclin-dependent kinase 10 (Cdk10) is a Cdc2-related kinase and plays an essential role in the progression from the G2 to M phase of the cell cycle. However, relative little is known about its expression pattern, clinical relevance, and biological function in hepatocellular carcinoma (HCC). In the present study, we investigated the mRNA and protein expression levels of Cdk10 in 127 pairs of HCC samples and adjacent nontumorous liver tissues and evaluated its clinical significance. Additionally, we assessed the effects of restoration of Cdk10 on cell proliferation and drug sensitivity in HCC cells. We showed that the Cdk10 mRNA and protein expression was markedly decreased in HCC samples compared to adjacent nontumorous liver tissues. Quantitative real-time polymerase chain reaction and immunohistochemical studies revealed that reduced Cdk10 expression was significantly associated with alpha-fetoprotein levels, tumor size, and tumor stage. Ectopic expression of Cdk10 reduced HCC cell proliferation, blocked the cell cycle at the G0-G1 phase, as well as inhibited cell migration and anchorage-independent growth. Additionally, Cdk10 overexpression enhanced the chemosensitivity of HCC cells to cisplatin and epidoxorubicin, two chemotherapeutic agents commonly used in HCC. These data collectively demonstrate that reduced Cdk10 expression is closely linked to HCC development and progression. Restoration of its expression may have therapeutic benefits in treating this malignancy.

CDK10 functions as a tumor suppressor gene and regulates survivability of biliary tract cancer cells.

Cyclin-dependent kinase 10 (CDK10) is a member of the Cdc2 family of kinases, and has been demonstrated to be an important determinant of resistance to endocrine therapy for breast cancer. To investigate the expression and possible function of CDK10 in biliary tract cancer (BTC), we systematically examined CDK10 in tissues and cell lines. We found that expression of CDK10 was downregulated in both biliary tract tumors and cell lines. Remarkably, the expression of CDK10 correlated with clinical characteristics. Overexpression or knockdown of CDK10, respectively, inhibited or promoted cell proliferation, colony formation and migration. This suggests that CDK10 functions as a tumor suppressor gene in BTC. Overexpression of CDK10 caused malignant cells to become sensitive to chemotherapy and other hostile environments, suggesting that CDK10 functions to regulate survivability of BTC cells. We investigated the expression of six genes to resolve the mechanism. c-RAF was negatively regulated by CDK10 in both cells and specimens. Our results indicate that CDK10 plays a crucial role in the growth and survivability of biliary tract cancer, and offers a potential therapeutic target for this fatal disease.

MicroRNA-421 functions as an oncogenic miRNA in biliary tract cancer through down-regulating farnesoid X receptor expression.

MicroRNAs (miRNAs) are involved in the development of most cancers. However, few studies have been conducted to determine their relationship to biliary tract cancer (BTC). Farnesoid X receptor (FXR) has been reported to be a tumor suppressor for hepatocellular carcinoma and breast cancer; but few studies have focused on its correlation with BTC. In this study, we identified miR-421 as a potential regulator of FXR expression. We found that their expression amount was inversely correlated as FXR was aberrantly down-regulated in both primary tumor specimens and cell lines; while miR-421 was significantly up-regulated. Ectopic expression of miR-421 significantly decreased FXR protein concentration in BTC cells and promoted cell proliferation, colony formation and migration in vitro. Furthermore, a decrease in miR-421 expression induced G(0)/G(1) cell cycle arrest. In conclusion, our study identified microRNA-421 functions as an oncomiR in BTC by targeting FXR. This finding may provide a novel therapeutic strategy for treatment of biliary tract cancer.

IL-6/STAT3/TFF3 signaling regulates human biliary epithelial cell migration and wound healing in vitro.

Interleukin-6 (IL-6), through activation of the signal transducer and activator of transcription 3 (STAT3) and trefoil factor family 3 (TFF3), has been implicated in the promotion of mouse biliary epithelial cell (BEC) proliferation and migration. However, it is still unclear whether the IL-6/STAT3/TFF3 signaling had similar effects on human BECs. Here, we showed that exposure of human BECs to recombinant IL-6 resulted in STAT3 phosphorylation and increased the expression of TFF3 at both mRNA and protein levels. Moreover, inhibition of STAT3 using RNA interference significantly abrogated IL-6-induced TFF3 expression. In an in-vitro wound healing model, IL-6 facilitated human BEC migration. This promotion of cell migration by IL-6 was blocked when STAT3 was knocked down. Interestingly, the addition of exogenous TFF3 could rescue the cell migration defects caused by STAT3 silencing. In conclusion, our data indicate that STAT3 plays a critical role in IL-6-induced TFF3 expression in human BECs and the IL-6/STAT3/TFF3 signaling is involved in human BEC migration and wound healing.

Reconstitution of secreted frizzled-related protein 1 suppresses tumor growth and lung metastasis in an orthotopic model of hepatocellular carcinoma.

BACKGROUND: Secreted Frizzled-related protein 1 (sFRP1) is frequently silenced in many types of cancer, including hepatocellular carcinoma (HCC), leading to aberrant activation of Wnt signaling and thereby facilitating tumor development. In this study, we aimed to investigate whether restoration of sFRP1 affected HCC growth and metastasis. METHODS: We generated stable cell lines overexpressing sFRP1 in MHCC97-H cells, which naturally do not express detectable sFRP1 messenger RNA (mRNA) and have high metastatic properties. The effects of sFRP1 reexpression on tumor growth and metastasis were assessed in vitro and in vivo. It was also tested whether ß-catenin signaling mediated the function of sFRP1 in tumor progression. RESULTS: Overexpression of sFRP1 substantially diminished the proliferation and invasion potentials of MHCC97-H cells. Furthermore, sFRP1 expression significantly inhibited MHCC97-H xenograft growth and metastasis in vivo, which was accompanied by decreased angiogenesis and increased tumor cell apoptosis. Moreover, sFRP1 overexpression caused less expression of ß-catenin and its downstream effector genes cyclin D1 and matrix metalloproteinase (MMP)-2. CONCLUSION: Together these findings demonstrate that sFRP1 reconstitution suppresses tumor growth, angiogenesis, and metastasis in MHCC97-H xenografts, which may be associated with inactivation of ß-catenin signaling, thus providing a possible therapeutic strategy against HCC.

Use of a cocktail regimen consisting of soluble galectin-1, rapamycin and histone deacetylase inhibitor may effectively prevent type 1 diabetes.

Type 1 diabetes (T1D) is an autoimmune disorder that results in destruction of insulin-releasing beta-cells of the pancreas. During the pathogenesis of T1D, at least two phases of beta-cell death occur: an initiation event wherein macrophage-derived inflammatory cytokines induce beta-cell necrosis and release of beta-cell-specific antigens, and a second, antigen-driven event in which T-cell-mediated immune response is directed against beta-cells. In contrast to macrophages and autoreactive T cells, regulatory T cells play a key role in inducing and maintaining immunological tolerance to self antigens. Therefore, modulation of the immune system may prevent the development of T1D. Herein, we proposed a cocktail regimen consisting of soluble galectin-1, rapamycin and histone deacetylase inhibitor (HDACi) for the treatment of T1D because (a) HDACi has been reported to protect against IL-1beta-mediated loss in beta-cell viability, (b) HDACi and rapamycin have the ability to promote the generation and function of regulatory T cells and thus suppress the cytotoxic T-cell function, and (c) administration of soluble galectin-1 can trigger apoptosis of the beta-cell-reactive T cells. This cocktail regimen may not only block T-cell- and cytokine-mediated autoimmunity but also restore self-tolerance to beta-cell antigens, therefore representing a novel alternative for treatment of T1D.

Case-control studies on debridement combined with external application of Mangxiao for the treatment of severe open injuries of limbs / 中国骨伤

<p><b>OBJECTIVE</b>To investigate simple and convenient methods for the treatment of severe open injuries of limbs.</p><p><b>METHODS</b>From 2005.1 to 2008.3, 31 patients got limb salvage in 33 cases (Gustilo III B) from emergency, which were divided into two groups(A and B). The 16 patients in Group A (14 male and 2 female) were treated with emergency debridement, sequential dressing change, and finally with skin grafting or free flap. The 15 patients in Group B (11 male and 4 female) were treated with radical debridement (skin and muscle), decompression of fascial compartment routinely and repair of periosteal avulsion lesion. The patients in Group B were also treated with external application of Mangxiao postoperatively and dressing change for first time one week later. The clinical effects were assessed by the skin survival rate of degloving injury, the number of operative procedures (using free flap or not), the number of dressing changes in the first two weeks, body temperature and white cell count (48 h after the first debridement ). Statistical analysis was done with SPSS software. Chi-square analyses was used to compare the enumeration data, and compare means with independent samples T test for measurement data.</p><p><b>RESULTS</b>All the patients in Group A got limb salvage (10 patients were upper limb, 6 patients were lower limb), and the mean skin survival rate of degloving injury was (77.88 +/- 4.21)%. Five patients in Group A were finally treated with free flap. All the patients in Group B got limb salvage (10 patients were upper limb, 5 patients were lower limb) by a few secondary skin grafting, and the mean skin survival rate of degloving injury was (97.53 +/- 3.09)%. The mean skin survival rate of Group B was obviously better than that of Group A (P<0.01). The number of dressing changes in the first two weeks in Group B was absolutely less than that of Group A (P<0.01). Also, infection rate and the number of operative procedures of Group B was significantly less than that of Group A (P<0.01). All the patients were followed up for at least 3 months.</p><p><b>CONCLUSION</b>Radical debridement combined with external application of Mangxiao for the treatment of severe open fractures is simple, convenient and effective. It is better for a lot of people injured simultaneously in accident.</p>

Experience of congenital choledochal cyst in adults:treatment, surgical procedures and clinical outcome in the Second Affiliated Hospital of Harbin Medical University.

This study was undertaken to analyze and evaluate the diagnosis and principal treatment methods for congenital choledochal cyst, focusing on various surgical procedures and clinical outcome. A comprehensive, retrospective study was conducted on 72 adult patients who presented with choledochal cyst from 1985 to 2002. Surgical procedures were cyst excision with hepaticojejunostomy in 25 cases for type I or type IV-B, extrahepatic cyst excision with hepaticojejunostomy in 8 cases for type IV-A, extrahepatic cyst excision with modified hepaticojejunostomy in 2 cases for type IV-B, non-cyst excision with or without hepaticojejunostomy in 27 cases for types I, II, IV-A, IV-B. The early postoperative morbidity and mortality rate were 16.1% (9/62) and 6.5% (4/62) respectively, and the complication rate related to surgical procedure was 30.6% (19/62). The incidence of cholangiocarcinoma with non-cyst excision or non-operated congenital choledochal cyst was 10.8% (4/37). One patient died of primary hepatocellular carcinoma after cyst excision with hepatojejunostomy. In conclusion, our results showed that complete excision of choledochal cyst for types I, II, and IV-B and complete excision of extrahepatic choledochal cyst from the hepatic hilum in type IV-A with hepaticojejunostomy or modified hepaticojejunostomy are the treatment of choice for choledochal cyst in adult patients.