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This study was to evaluate the effect of pelvic floor muscle training (PFMT) on urinary incontinence (UI) in prenatal and postnatal women. The relevant literatures were searched from Pubmed, Embase, Cochrane Library, and Web of Science until January 20, 2020. Meta-analysis was performed with STATA 15.1 and the Begg’s test was used for the publication bias. Results of the meta-analysis demonstrated that the rate of UI in the intervention group was lower than that in the control group [relative risk (RR): 0.712, 95%confidence intervals (CI): 0.622–0.816, P

Background Cipatinib is a novel tyrosine kinase inhibitor against both EGFR and HER2/neu. This phase I trial was conducted to assess the safety, dose‐limiting toxicities (DLTs), and maximum‐tolerated dose of cipatinib in HER2‐positive patients with advanced breast cancer. Methods Eligible adults with advanced breast cancer were administered cipatinib 200 mg/day (n = 3) as an initial dose, with escalating dosages of 400 mg (n = 4), 800 mg (n = 2), 1200 mg (n = 3), 1400 mg (n = 3), 1600 mg (n = 3), and 1800 mg (n = 2) in 21 day cycles. DLTs were monitored until the end of cycle 2. Physical examinations, vital signs, blood sampling for hematology, clinical chemistry, and pharmacokinetics were performed throughout the trial. Results Of the 26 subjects enrolled, 23 completed the trial. A total of 143 adverse events (AEs) were reported, of which 87 were associated with cipatinib treatment and comprised: neutropenia (38%), hypertriglyceridemia (15%), fatigue (15%), nausea (12%), fever (19%), and myocardial ischemia (19%). Six AEs were graded 3–4 (neutropenia, increases in aspartate aminotransferase, and total bilirubin, fatigue, dizziness and nodal tachycardia), but none of the AEs observed were considered to be DLTs. Conclusion This tolerability study revealed that despite a mild toxicity profile, cipatinib was well tolerated up to the anticipated maximum dosage of 1800 mg/m2. Further clinical trials are warranted.

Background Currently, there are no standard regimens for metastatic breast cancer patients (MBC) who have failed ≥ 3 chemotherapy treatments. The aim of this study was to assess whether weekly low‐dose bevacizumab‐based regimens were well tolerated and would improve efficacy in MBC patients who had failed numerous therapies. Methods Seventeen patients with MBC who were heavily pretreated with a median of five regimens of therapy (range 1–10) between 2012 and 2016 were included in the analysis. Bevacizumab was administered at a dose of 100 mg intravenously once a week combined with one or two types of chemotherapeutic drugs until confirmed disease progression or an intolerable adverse event was observed. Patient characteristics, objective response rate, clinical benefit rate, progression‐free survival, and toxicity were assessed. Results All 17 patients had been pretreated with taxane‐based and anthracycline‐based chemotherapy. Weekly low‐dose bevacizumab combined with one or two types of chemotherapeutic drugs, which had usually not been previously used (e.g. etoposide, irinotecan, pemetrexed, methotrexate, and nab‐paclitaxel), was administered. Three patients achieved a partial response, while one had stable disease for > 24 weeks, and the clinical benefit rate was 23.5%. Median progression‐free survival was 3.4 months (95% confidence interval 2.0–4.8). The most common hematological adverse events were neutropenia, anemia, and thrombocytopenia. Bevacizumab‐related adverse events included grade 1 bleeding (17.6%) and grade 2 hypertension (5.9%). Conclusions Weekly low‐dose bevacizumab combined with chemotherapy shows a relatively favorable clinical response and tolerable toxicity, providing a feasible option for heavily pretreated MBC patients.

To explore and compare the safety depths of perpendicular and oblique acupuncture at Yamen (GV 15) in patients with atlantoaxial dislocation (AAD) and healthy volunteers.One bundred and seventy-seven patients with atlantoaxial dislocation were selected as an AAD group, and 207 patients without atlantoaxial dislocation and with normal anatomical structure were selected as a normal group. All participants were moderately sized. The MRI scanning of the cervical vertebra was performed, and the safety depth of perpendicular and oblique acupuncture at Yamen (GV 15) was calculated on the sagittal image.In the AAD group, the safety depth of men was (45.33±5.17) mm for perpendicular acupuncture and (48.58±4.41) mm for oblique acupuncture; the safety depth of women was (44.17±7.80) mm for perpendicular acupuncture and (47.49±7.32) mm for oblique acupuncture. In the normal group, the safety depth of men was (47.72±5.06) mm for perpendicular acupuncture and (42.69±5.53) mm for oblique acupuncture; the safety depth of women was (44.63±5.85) mm for perpendicular acupuncture and (39.88±6.18) mm for oblique acupuncture. The safety depth of men and women for oblique acupuncture was longer than that for perpendicular acupuncture in the AAD group (The safe depth of acupuncture at Yamen (GV 15) has significantly changed under AAD, so during the clinical acupuncture the needle insertion should be less than its safe depth.

OBJECTIVE: To investigate the clinical features and prognosis of acute renal failure (ARF) caused by rhabdomyolysis (RM) in children. METHODS: A retrospective analysis was performed for the clinical data, laboratory examination, and prognosis of 26 RM children with ARF. RESULTS: The causes for all 26 RM children with ARF were non-traumatic diseases, and the three most common causes were infection (69%), diabetes (12%), and metabolic disease (8%). In the RM children with ARF, the five most frequent clinical manifestations were fever (69%), multiple organ dysfunction syndrome (69%), convulsion (46%), oliguria or anuria (35%), and tea-colored urine (27%). All 26 children had a serum creatine kinase (CK) level of >1 000 IU/L, among whom 26 had increased aspartate aminotransferase, 25 had increased alanine aminotransferase, 25 had increased creatine kinase isoenzyme, and 23 had increased lactate dehydrogenase. Serum myoglobin (Mb) was measured in 22 children and was found to increase in all these children. The mean time for CK to decrease to below 1 000 IU/L was 10±5 d. There was no significant difference in the time to CK recovery between the 10 children who were treated with conventional treatment as well as continuous venous-venous hemofiltration and those who were not treated with blood purification (P > 0.05). Of all 26 RM children with ARF, 7 were withdrawn from the treatment, and 19 had normal renal function after treatment. CONCLUSIONS: ARF and multiple organ dysfunction syndrome are major complications in RM children. The major primary disease for RM children with ARF is infectious disease. CK is the major marker for the diagnosis of RM. Early diagnosis and appropriate treatment may reverse ARF and improve prognosis.

Liver transplantation for autoimmune hepatitis (AIH) is usually successful with excellent long-term outcomes, but primary disease may recur. The recurrence of AIH is a significant cause of graft loss. This study was to analyze the effect of splenectomy in preventing AIH relapse. The clinical courses of 12 patients who had transplantation for AIH were analyzed retrospectively. All patients were subjected to transplantation for end-stage liver disease caused by chronic AIH. Based on the duration of immunosuppressive treatment before liver transplantation, simultaneous splenectomy was performed in ten patients. Two patients underwent liver transplantation without splenectomy, one of them developed recurrent AIH and died from graft failure caused by AIH relapse. However, no episode of AIH recurrence was observed in patients who had undergone simultaneous splenectomy. Splenectomy might be an option to prevent AIH relapse in some patients with high risk factors.

Increasing evidence has been accumulated for the effectiveness of acupuncture therapy in relieving pain. However, there are limited data on regulation of protein expression after electroacupuncture (EA) intervention. Thus, the present study is designed to determine changes in protein expression following EA stimulation in rats with sciatic nerve chronic constrictive injury (CCI) induced neuropathic pain. Sixty Wistar rats were equally randomized into normal control group, CCI group, and CCI with EA stimulation (EA) group. The CCI model was established by ligature of the left sciatic nerve. EA stimulation was applied at Zusanli (ST36) and Yanglingquan (GB34) in the EA group. Differentially expressed hypothalamic proteins in the three groups were identified by 2-D gel electrophoresis and matrix-assisted laser desorption/ionization time of flight mass spectrometry. The functional clustering and pathway of the identified proteins were analyzed by Mascot software. Results showed that, after CCI, the thermal pain threshold of the affected hind footpad was decreased and was reversed gradually by 12 sessions of EA treatment. Following EA intervention, there were 17 hypothalamic proteins identified with significant changes in the expression (>twofold). Three gene-ontologies (oxidoreductase activity, oxidation reduction, and protein binding) were enriched, while there was a significant regulation of glycolysis/gluconeogenesis/hexose metabolism pathway. These data demonstrate that EA intervention can attenuate pain via regulation of expression of multiple proteins in the hypothalamus. Further, hypothalamic glucose metabolism may be important in supporting energy and neurotransmitter homeostasis in the effects of EA intervention.

AIM To analyze retrospectively a 5-year experience of human hepatocyte isolation from resected liver tissues with benign disease. METHODS We established a method of modified four-step retrograde perfusion to isolate primary human hepatocytes. Samples were collected from the resected livers of patients with intrahepatic duct calculi (n = 7) and liver hemangioma (n = 17). Only the samples weighing ≥ 15 g were considered suitable for hepatocyte isolation. By using the standard trypan blue exclusion technique, hepatocyte viability and yield were immediately determined after isolation. RESULTS Twenty-four liver specimens, weighing 15-42 g, were immediately taken from the margin of the removed samples and transferred to the laboratory for hepatocyte isolation. Warm ischemia time was 5-35 min and cold ischemia time was 15-45 min. For the 7 samples of intrahepatic duct calculi, the method resulted in a hepatocyte yield of 3.49 ± 2.31 × 106 hepatocytes/g liver, with 76.4% ± 10.7% viability. The 17 samples of liver hemangioma had significantly higher yield of cells (5.4 ± 1.71 × 106 cells/g vs 3.49 ± 2.31 × 106 cells/g, P < 0.05) than the samples of intrahepatic duct calculi. However, there seems to be no clear difference in cell viability (80.3% ± 9.67% vs 76.4% ± 10.7%, P > 0.05). We obtained a cell yield of 5.31 ± 1.87 × 106 hepatocytes/g liver when the samples weighed > 20 g. However, for the tissues weighing ≤ 20 g, a reduction in yield was found (3.08 ± 1.86 × 106 cells/g vs 5.31 ± 1.87 × 106 cells/g, P < 0.05). CONCLUSION Benign diseased livers are valuable sources for large-number hepatocyte isolation. Our study represents the largest number of primary human hepatocytes isolated from resected specimens from patients with benign liver disease. We evaluated the effect of donor liver characteristics on cell isolation, and we found that samples of liver hemangioma can provide better results than intrahepatic duct calculi, in terms of cell yield. Furthermore, the size of the tissues can affect the outcome of hepatocyte isolation.

To observe the effects of repeated electroacupuncture (EA) of Zusanli (ST36)- Yanglingquan (GB34) on hypothalamic acetylcholinesterase (AchE) and vesicular acetylcholine (ACh) transporter (VAChT) activities and choline acetyltransferase (ChAT) mRNA and muscarinic M1 receptor (M1R) mRNA expression in chronic constrictive injury (CCI) and/or ovariectomy (OVX) rats so as to reveal its underlying mechanism in cumulative analgesia.A total of 103 female Wistar rats were randomly divided into normal control (n =15), CCI (n =15), CCI+EA2d (n =15), CCI+EA2W (n =15), OVX+CCI =13), OVX+CCI+EA2d (n =15), and OVX+CCI+EA2W groups (n =15). CCI model was established by ligature of the unilateral sciatic nerve with surgical suture. Memory impairment model was established by removal of the bilateral ovaries. Morris water test was conducted to evaluate the OVX rats' memory learning ability, and the thermal pain threshold (PT) of the bilateral paws was detected the next morning after EA. EA (2/15 Hz, 1 mA) was applied to bilateral ST36-GB34 for 30 min, once daily for 2 days or 2 weeks, respectively. Hypothalamic AChE activity was detected by histochemistry, VAChT immunoactivity was determined by immunohistochemistry, and ChAT mRNA and M1R mRNA expressions were assayed by reverse transcription-polymerase chain reaction (RT-PCR).In comparison with the normal control group, the AChE activity in hypothalamic arcuate nucleus (ARC) and supraoptic nucleus (SON) regions of CCI group, AChE activity in paraventricular nucleus (PVN), ARC, and SON regions of OVX+CCI group, and hypothalamic muscarinic M1R mRNA expression levels in both CCI and OVX+CCI groups were down-regulated significantly (P0.05). Compared with the CCI group, the AChE activities in hypothalamic ARC and SON regions of CCI+EA2d and CCI+EA2W groups and PVN region of CCI+EA2W group and hypothalamic ChAT mRNA and M1R mRNA expression levels in CCI+EA2W group were up-regulated considerably (P0.05). In comparison with the OVX+CCI group, the AChE activities in PVN, ARC, and SON regions and the expressions of hypothalamic ChAT mRNA and VAChT in ARC region of OVX+CCI+EA2W group were up-regulated remarkably (P0.05). The effects in rats of CCI+EA2W group were evidently superior to those of OVX+CCI+EA2d group in up-regulating AChE activities in PVN, ARC, and SON regions, VAChT immunoactivity in ARC region, and expression levels of hypothalamic ChAT mRNA and M1R mRNA (P0.05). Similar situations were found in OVX+CCI rats after EA2W. It suggested a cumulative effect after repeated EA of ST36-GB34. Comparison between CCI+EA2W and OVX+CCI+EA2W groups showed that the effects in rats of the former group were evidently better than those of the latter group in up-regulating AChE activity in ARC and SON regions and the expressions of hypothalamic ChAT mRNA and M1 mRNA (P0.05), suggesting a reduction of EA2W effects after OVX.Repeated EA can significantly up-regulate AChE and VAChT activities and ChAT mRNA and M1R mRNA expressions in the hypothalamus of CCI and OVX+CCI rats, which may contribute to the cumulative analgesic effects of repeated EA and be closely related to the animals' neuromemory ability.

Brain-specific metastasis occurs frequently in lung cancer, and the mechanism is still unclear. The present study was designed to investigate the correlation between CXCR4 expression and brain-specific metastasis of non-small cell lung cancer. The brain metastatic tumors and lung cancer tissues from 32 patients with solitary brain metastasis of non-small cell lung cancer (M1 group), who underwent combined surgical treatment from January 1998 to June 2008, and 32 paired patients without distant metastasis (M0 group) and 30 patients with primary brain tumor, were examined by immunohistochemistry to detect the expression of CXCR4 protein. The difference of CXCR4 expression was compared by the McNemar χ2 test or Fisher’s exact test. Estimation of survival was calculated with the Kaplan–Meier method, and the statistical differences were analyzed with the log-rank test. Overexpression of CXCR4 protein was observed in 29 (90.6%) M1 non-small cell lung cancers and in all (100%) brain metastatic tumors, which was significantly higher than that in the paired M0 non-small cell lung cancer and the primary brain tumors, respectively (p = 0.000). The 3- and 5-year cumulative survival rates of patients with solitary brain metastasis of lung cancer were 21.9 and 12.5%, significantly lower than the corresponding survival rates of M0 group patients (p = 0.005). CXCR4 protein was highly overexpressed in M1 non-small cell lung cancer and brain metastatic tumors, which indicated that high-level CXCR4 expression correlates with brain-specific metastasis of non-small cell lung cancer.

Genetic polymorphism of IFNAR-1 plays a large role in determining the clearance or chronicity after hepatitis B virus (HBV) exposure. However, it is not clear whether type I interferon receptor-1 (IFNAR-1) variations continuously exert their effects to influence the final outcomes following HBV chronicity, including acute-on-chronic hepatitis B liver failure (ACLF-HBV), chronic hepatitis B (CHB), liver cirrhosis (LC), and hepatocellular carcinoma (HCC). Here we report that these four potential outcomes of chronic HBV infection are strongly associated with IFNAR-1 polymorphisms through a hospital-based case-control study of 663 cases. ACLF-HBV and HCC were each compared with CHB+LC. In comparison with the G/G genotype, the C/G and C/C genotypes at both single-nucleotide polymorphism (SNP) sites (rs1012335 and rs2257167) showed significant susceptibility to ACLF-HBV (the highest odds ratio [OR] reached 2.374; 95% CI = 1.488, 3.788; p0.001 for the C/G genotype at rs2257167), as well as HCC (OR = 2.475; 95% CI = 1.435, 4.426; p0.001 for the C/C genotype at rs1012335). The C allele at both loci was a susceptibility allele for ACLF-HBV and HCC, with the highest ORs reaching 1.653 (95% CI = 1.233, 2.216; p0.01 at rs1012335) in the ACLF-HBV group, and 1.659 (95% CI = 1.274, 2.159; p0.01 at rs1012335) in the HCC group. A strongly linked disequilibrium was also found within these two alleles (p0.001). Our research indicates that genetic polymorphisms of IFNAR-1 not only contribute to the determination of clearance or chronicity in the early stages of HBV exposure, but they also persistently influence pathogenesis over the long-term process of chronic HBV infection.

This 8-week, randomized, placebo-controlled, double-blind clinical study investigated the short-term effectiveness and safety of the traditional Chinese medicine, Ningdong (ND) granule in paediatric subjects (aged 7-18 years) with Tourette's disorder (TD). Subjects received either 1 g/kg per day ND granule ( n = 33) or placebo ( n = 31) and tics were measured at baseline and after 4 and 8 weeks of treatment. Body mass index, electrocardiogram and laboratory measures were recorded at baseline and at week 8. After 8 weeks of treatment with ND granule, subjects exhibited a 41.39% reduction in the total tic score while the placebo group showed a 10.79% decrease. Regarding side-effects, two subjects reported loss of appetite and one experienced constipation in the ND granule group. There were no significant changes in laboratory and physical examinations. These results suggest that ND granule is both effective and safe, and may be a good candidate for the treatment of patients with TD.

The purpose of the present study was to investigate the complications, long-term survival, and management lessons learned after surgical resection for patients with primary tumors of the trachea and carina and locally advanced lung cancer directly infiltrating the carina.A retrospective study was performed by our department on 32 patients undergoing surgical resection for primary tumors of the trachea and carina and locally advanced lung cancer directly infiltrating the carina between June 1986 and June 2003.Various surgical modalities were performed according to the tumor location and extent: tracheal resection in 10 cases, carinal resection and reconstruction in 4 cases, carinal right upper lobectomy in 8 cases, carinal pneumonectomy in 4 cases, and partial tangential resection of the tracheal wall in 6 cases. Cardiopulmonary bypass was required in two patients for nearly complete obstruction of the trachea. Resected tumors included six distinct histologic types. Perioperative mortality was 9.4% (3/32). Major complications occurred in 31.3% (10/32) of the patients. The overall 1-, 3-, and 5-year survival rates were 87.5%, 56.3%, and 40.6%, respectively. Patients with primary tracheal and carinal tumors experienced a 5-year survival of 55.0% compared to 16.7% for those with locally advanced lung cancer directly infiltrating the carina (P0.05).Surgical resection is the most effective treatment of choice for primary tumors of the trachea and carina. With careful patient selection and meticulous surgical and anesthesia techniques, the operative mortality and complications are acceptable, and long-term survival can be achieved.

There are few reports about abdominal lymph node metastasis of mid thoracic esophageal carcinoma. This study was designed to explore the pattern of abdominal lymph node metastasis in patients with mid thoracic esophageal squamous cell carcinoma and to evaluate the prognostic factors.The complete data of 368 patients with mid thoracic esophageal squamous cell carcinoma, who underwent modified Ivor-Lewis esophagectomy with two-field lymphadenectomy from January 1998 to January 2003, were reviewed. Survival rate was calculated by Kaplan-Meier method. Cox regression analysis was performed to identify risk prognostic factors.Abdominal lymph node metastasis occurred in 58 (15.8%) patients: 34.5% (20/58) of them were stage T1 and T2. Skipping abdominal node metastasis was recognized in 13.8% (8/58) patients: all were stage T1 and T2. The overall 5-year survival rate of patients with abdominal lymph node metastasis (10.3%) was lower than that of those with thoracic node metastasis (18.3%). The prognosis of patients with distant abdominal lymph node metastasis was poor, and no one could survive more than 5 years. Cox regression analysis showed that five or more positive nodes and distant abdominal node metastasis were independent risk factors of patients with abdominal lymph node metastasis.Abdominal lymph node metastasis in patients with mid thoracic esophageal squamous cell carcinoma occurred frequently, and the surgery favorable for extensive abdominal lymph node dissection should be selected. The prognosis of patients with abdominal lymph node metastasis was poor, especially those with more positive nodes and distant abdominal node metastasis.

To investigate the prevalence of lymph node micrometastasis (LNMM) on the basis of the detection of MUC1 mRNA, and assess the impact of these micrometastases on disease-free interval after resection of pathologic N0 (pN0) esophageal squamous cell cancer (ESCC).The subjects were 93 patients who underwent complete resection of pN0 ESCC at our department between January 1999 and January 2001. All lymph nodes (426 stations) obtained from these patients were reevaluated by reverse transcription-polymerase chain reaction to detect MUC1 mRNA. The diagnosis of LNMM was based on the detection of MUC1 mRNA. A log-rank test was performed to compare the disease-free interval, and Cox regression multivariate analysis was performed to determine the independent prognostic factors.Micrometastasis was detected in 40 lymph node stations (9.4%) from 32 patients (34.4%). Disease-free interval was significantly associated with LNMM (P = 0.0138). The 5-year survival rate of patients with LNMM was significantly lower than that of those without LNMM (P = 0.004). The results of multivariate analysis confirmed that T status and LNMM were independent prognostic factors.The prevalence of LNMM in patients with pN0 ESCC was 34.4% (32/93). Thus, LNMM was significantly associated with the disease-free interval. T status and LNMM were both independent prognostic factors.

To investigate the healing mechanism of the rabbit's sclerotomy sites undergoing the Transconjunctival Sutureless Vitrectomy (TSV).Thirty-two rabbits (Thirty-two eyes) were divided into four groups: The rabbits performed with the core vitrectomy and air tamponade were Group A, performed with the core vitrectomy as Group B, performed with the non-core vitrectomy and air tamponade as Group C, and the non-core vitrectomy as Group D. The sclerotomy sites were observed by the Ultrasound Biomicroscope (UBM model 840, Humphrey Instruments, San Leandro, CA, USA) on days 1, 3, 5, and 9 postoperatively, and the diameter of the internal and the external aperture was estimated on postoperative day 1. The pathological study of the sclerotomy sites on days 3, 5, and 9 postoperatively were investigated under the light microscope.The Ultrasound Biomicroscope and the pathological sections showed that the healing course of the sclerotomy sites lasted nine days. On postoperative day 1, the vitreous incarceration (19/32, 59.4%), the fluid cavity (18/32, 56.3%), and the air cavity under the conjunctiva (7/16, 43.8%) existed in some cases. The diameter of the internal aperture in Group A and Group B was less than Group C and Group D on day 1 postoperatively, P0.001. The diameter of the external aperture did not show significant difference in any of the groups. The pathological study verified the healing course was the granulation reaction.The healing mechanism of the rabbit's sclerotomy sites undergoing the (TSV) is the granulation reaction accompanied with the elastic recovery of the sclera.

Single progesterone receptor positive (PgR+), especially in form of ER−/PgR+/HER2−, is a nonnegligible phenomenon. Little is known about the characteristics and the role of single PgR positive in this phenotype. Therefore, we explore the significance of single PgR positivity by comparing ER−/PgR+/HER2− breast cancers with triple negative breast cancers (TNBCs). Three thousand nine hundred sixty-six cases of primary invasive breast carcinoma operated consecutively from January 2005 to May 2008 in Cancer Hospital, Chinese Academy of Medical Sciences were examined. Two hundred forty (6%) cases were identified as ER−/PgR+/HER2− breast cancers and 348 (8.8%) cases as TNBCs. Clinicopathological characteristics and survivals were analyzed respectively and then compared between 2 subtypes. Compared with patients with TNBCs, ER−/PgR+/HER2− tumor tended to have lower tumor grade (Grade 3: 45.7% vs. 37.5%, P = 0.051) and smaller tumor size (P = 0.036). However, no differences were found between ER−/PgR+/HER2− and TNBC patients in relapse-free survival (RFS) and OS. The 5-year RFS rates were 80.7% and 77.4%, respectively (P = 0.330) and the 5-year OS rates were 88.0% and 85.2%, respectively (P = 0.290). ER−/PgR+/HER2− patients receiving adjuvant endocrine treatment had better RFS (P = 0.016) and overall survival (OS) (P

Recognition of evolutionarily conserved ligands by Toll-like receptors (TLRs) triggers signaling cascades in innate immune cells to amplify adaptive immune responses. Nearly all TLRs require MyD88 to transduce downstream signaling. MyD88 deficiency has been shown to promote the allograft acceptance in mice. However, direct evidence for therapeutic potential of MyD88 inhibitors remains lacking. Herein, we used a MyD88 inhibitor, namely ST2825, to explore its therapeutic potential and mechanisms in fully allogeneic skin and heart transplant models. Phenotypic maturation of dendritic cells stimulated by TLR ligands was alleviated by ST2825 in parallel with reduced T-cell proliferation in vitro. A short-course treatment with ST2825 significantly prolonged cardiac graft survival (mean survival time = 18.5 ± 0.92 days vs. 7.25 ± 0.46 days). ST2825-treated group had significantly reduced proinflammatory cytokines in allografts compared with control group. ST2825 combined with anti-CD154 induced long-term skin allograft acceptance in about one-third of recipients (>100 days). 'Skin-tolerant' recipients showed attenuated donor-specific IFN-γ responses, intact IL-4 responses, and compromised alloantibody responses. We conclude that MyD88 inhibitor ST2825 attenuates acute cardiac rejection and promotes donor-specific hyporesponsiveness in stringent skin transplant models. The direct evidence suggests that pharmacological inhibition of MyD88 hold promising potential for transplant rejection.

Objective: Bevacizumab is the only anti-angiogenic agent approved in first-line therapy for metastatic colorectal cancer (mCRC). Although chemotherapy plus bevacizumab has led to improve outcomes for mCRC patients and is a common choice for first-line treatment of mCRC, previous research has established no prominent biomarker that can help to select patients who may benefit from bevacizumab in order to improve cost-effectiveness and therapeutic outcomes. The aim of this study was to compare pre- and post-therapeutic VEGF immunohistochemical (IHC) expression in mCRC patients treated with FOLFIRI plus bevacizumab to identify its potential role as a predictive biomarker. Methods: A total of 57 mCRC patients who underwent FOLFIRI combined with bevacizumab chemotherapy as a first-line neoadjuvant regimen were enrolled and clinical outcome data analyzed. Results: Low post-therapeutic VEGF expression (P < 0.001) and decreased peri-therapeutic VEGF expression (P < 0.001) were significantly predictive factors of responders. Furthermore, the 6-month progression-free survival (PFS) rate in mCRC patients with decreased peri-therapeutic VEGF expression was significantly better than the rate for those patients with no peri-therapeutic VEGF expression alterations (P = 0.033). Conclusions: Decreased peri-therapeutic VEGF expression in mCRC patients could probably be used to predict responsiveness to bevacizumab and subsequent PFS in clinical practice.

A large infarct-related artery (IRA), which mostly contains high-burden thrombus formation (HBTF) and lipid pool-like plaque contents, has been suggested to play a pivotal role in the no-reflow phenomenon during primary percutaneous coronary intervention (p-PCI). To reduce the thrombus burden of the IRA using the PercuSurge GuardWire device before intervention may be of crucial importance to preventing no-reflow. The purposes of this study were to test the transradial application (TRA) of this new mechanical device and to determine its impact on prevention of no-reflow during p-PCI. From May to September 2002, the PercuSurge GuardWire device was utilized in 42 consecutive patients with acute myocardial infarction and large IRA (vessel sizeor= 3.5 mm with HBTF; group 1). From January to December 2000, p-PCI was performed in large IRA (vessel sizeor= 3.5 mm) with HBTF using tranfemoral arterial approach in 101 consecutive patients (group 2). The angiographic and clinical outcomes of the two groups were compared in a chronologically consecutive manner. Successful reperfusion (final TIMI-3 flow) was significantly higher in group 1 than in group 2 patients (95.2% vs. 79.1%; P = 0.005). Moreover, the combined incidence of vascular complications, post-PCI thromboembolisms (defined as a distal embolism and a post-PCI residual thrombus score ofor= 3), and combined 30-day major adverse cardiac events were significantly lower in group 1 than in group 2 patients (all P values0.05). In group 1 patients, post-p-PCI myocardial blush (MB) ofor= 2 grades was found to be more than 88.0%. Furthermore, when compared with preintervention, thrombus scores were significantly reduced after aspiration (P = 0.0001), whereas the minimal lumen diameter (P = 0.0001), TIMI flow grade (P = 0.0001), and MB grade (P = 0.0001) had all significantly increased after aspiration using Export Aspiration Catheter. There were no significant differences in corrected TIMI frame count (P = 0.42), TIMI flow grade (P0.5), or MB grade (all P values0.5) between postaspiration and post-PCI. The TRA of the PercuSurge GuardWire device during primary intervention of large IRA with HBTF was safe and feasible and provided benefits to patients. The initial successful reduction of the thrombus burden with this mechanical device before intervention can be translated into increased final TIMI-3 flow, a combined MB ofor= 2 grades, and fewer final thromboembolic events.

Genome-wide association studies (GWAS) have identified several single-nucleotide polymorphisms (SNPs) at the PARK16 locus that can modulate the risk of Parkinson's disease (PD), including rs16856139, rs823128, rs823122, rs947211, rs823156, rs708730 and rs11240572. The strength of these associations has been investigated in people from several ethnic origins, including Europe, Chile, Japan, Taiwan and western China. The results have shown that an ethnicity-specific effect is an important consideration in such an analysis. Therefore, we genotyped the above seven SNPs using a case-control methodology to explore their association with the risk of PD in eastern China. A total of 456 study subjects comprising 226 patients with PD and 230 unrelated healthy controls were recruited. The minor allele frequencies at the rs16856139 and rs11240572 SNPs were found to be significantly higher in controls than in PD cases, which suggested that they conferred a protective effect against PD. Further analyses from more diverse ethnic origins are required to confirm the significance of rs16856139 and rs11240572.

Emergency department(ED) nurses work in a rapidly changing environment with patients that have wide variety of conditions. Occupational stress in emergency department nurses is a common problem. The purpose of this study was to describe the relationship between coping strategies and occupational stress among ED nurses in China. A correlational, cross-sectional design was adopted. Two questionnaires were given to a random sample of 127 ED nurses registered at the Heilongjiang Nurses' Association. Data were collected from the nurses that worked in the ED of five general hospitals in Harbin China. Occupational stress and coping strategies were measured by two questionnaires. A multiple regression model was applied to analyze the relationship between stress and coping strategies. The stressors of ED nurses mainly come from the ED specialty of nursing (2.97±0.55), workload and time distribution (2.97±0.58). The mean score of positive coping strategies was 2.19±0.35, higher than the norm (1.78±0.52). The mean score of negative coping strategies was 1.20±0.61, lower than the norm (1.59±0.66), both had significant statistical difference (P

To evaluate the therapeutic effect of warm acupuncture (moxa-heated acupuncture) needle stimulation of Waiguan (TE 5) acupoint in the treatment of shoulder-hand syndrome (phase I) in patients with stroke.Sixty stroke patients with shoulder-hand syndrome (phase I ) were equally randomized into control group and warm acupuncture group. Patients of the warm acupuncture group were treated by warm acupuncture stimulation of the affected TE 5 in combination with routine acupuncture stimulation of Jianyu (LI 15), Jianjing (GB 21), Quchi (LI 11), Wangu (SI 4), Yangchi (TE 4) and Hegu (LI 4), and rehabilitation training (passive and active upper-limb motion exercise for 30 min, once daily), and patients of the control group treated with routine acupuncture stimulation of the same acupoints mentioned above, and rehabilitation training. The treatment was conducted once daily, 5 times per week for two weeks. The patients' clinical conditions were evaluated by using Visual Analogue Scale (VAS, 0-10 points, shoulder pain degree), edema severity score (0 point:normal, 2 points: mild, 4 points: moderate, and 6 points: severe) and simplified Fugl-Meyer motor assessment scale (0, 1 and 2 points, upper-limb motor function) before and after the treatment.After the treatment, the scores of VAS and edema severity of the two groups were significantly decreased in comparison with pre-treatment in the same one group (P0.01), and the Fugl-Meyer motor scores were considerably increased (P0.01), suggesting an improvement of the shoulder-hand syndrome after two weeks' treatment. Of the two 30 patients in the control group and warm acupuncture group, 0 and 2 (6.7%) were cured, 7 (23.3%) and 25 (83.3%) experienced marked improvement, 17 (56.7%) and 2 (6.7%) were effective, 6 (20. 0%) and 1 (3.3%) invalid, with the effective rates being 80.0% and 96.7%, respectively. The effect of warm acupuncture group was superior to that of the control group (P0.05).Warm acupuncture combined with routine acupuncture and rehabilitation training is effective in improving shoulder pain, hand edema and limb motor function in stroke patients with shoulder-hand syndrome at phase I.

Pattern recognition receptors are attractive targets for vaccine adjuvants, and polymorphisms of the innate receptor NOD1 have been associated with allergic asthma.To elucidate whether NOD1 agonist may favor allergic asthma in humans through activation of dendritic cells, and to evaluate the mechanisms involved using an in vivo model.NOD1-primed dendritic cells from allergic and nonallergic donors were characterized in vitro on their phenotype, cytokine secretion, and Th2 polarizing ability. The in vivo relevance was examined in experimental allergic asthma, and the mechanisms were assessed using transfer of NOD1-conditioned dendritic cells from wild-type or CCL17-deficient mice.NOD1 priming of human dendritic cells promoted a Th2 polarization profile that involved the production of CCL17 and CCL22 in nonallergic subjects but only CCL17 in allergic patients, without requiring allergen costimulation. Moreover, NOD1-primed dendritic cells from allergic donors exhibited enhanced maturation that led to abnormal CCL22 and IL-10 secretion compared with nonallergic donors. In mice, systemic NOD1 ligation exacerbated allergen-induced experimental asthma by amplifying CCL17-mediated Th2 responses in the lung. NOD1-mediated sensitization of purified murine dendritic cells enhanced production of CCL17 and CCL22, but not of thymic stromal lymphopoietin and IL-33, in vitro. Consistently, adoptive transfer of NOD1-conditioned dendritic cells exacerbated the Th2 pulmonary response in a CCL17-dependent manner in vivo.Data from this study unveil a deleterious role of NOD1 in allergic asthma through direct induction of CCL17 by dendritic cells, arguing for a need to address vaccine formulation safety issues related to allergy.

Thymic carcinoma is reputed to carry a poor prognosis. Although few scholars have studied the prognosis of thymic carcinoma, the prognostic factors of patients after surgery are not well established. We analyze the prognostic significance of undetermined factors to predict the survival of patients after surgery. We reviewed 351 cases of thymic epithelial tumor treated with surgery at a single institution in China from 1992 to 2011. A total of 58 patients were histopathologically reconfirmed as having thymic carcinoma. Clinicopathological characteristics and treatment modalities were reviewed. During the follow-up, with a median of 65.8 months, survival time was analyzed using the Kaplan–Meier method. Univariate and multivariate analysis were performed to identify prognostic factors. The overall 3-, 5-, and 10-year survival rate was 69.0, 43.1, and 12.1 %, respectively. The Log-rank test revealed that Masaoka stage (p = 0.000), histology group (p = 0.000), completeness of the resection (p = 0.000), great vessel invasion (p = 0.000), and presence of symptoms (p = 0.003) were significant prognostic factors in all patients. However, tumor size (p = 0.086), age (p = 0.677), sex (p = 0.706), smoking (p = 0.065), and alcohol (p = 0.875) were not prognostic factors. A Cox proportional hazards regression model showed that Masaoka stage (hazard ratio = 15.640, p = 0.000) and completeness of the resection (hazard ratio = 18.303, p = 0.000) were the only independent prognostic factors. The Masaoka stage and completeness of the resection were independent prognostic factors that predicted long-term survival of patients with thymic carcinoma treated with surgery.

Objective To investigate the association between v-Ki-ras2 Kirsten rat sarcoma viral oncogene homologue ( KRAS) gene mutations and levels of human leucocyte antigen (HLA) class I antigen in primary lung tumours and metastatic lymph nodes of patients with non-small cell lung cancer (NSCLC). Methods Patients with NSCLC undergoing tumour resection were enrolled. KRAS codon 12 mutations were analysed in normal lung and lymph node tissue, primary lung tumours and metastatic lymph nodes using polymerase chain reaction–restriction fragment length polymorphism analysis. HLA class I antigen immunostaining was examined using flow cytometry. Results A total of 65 patients participated in the study. All normal lung tissues had positive HLA class I antigen immunostaining. The majority of primary lung tumours (56/65) and all of the metastatic lymph nodes (31/31) had downregulated HLA class I antigen immunostaining. There was a positive correlation between downregulated HLA class I antigen in primary tumours and metastatic lymph nodes. There was a negative correlation between KRAS codon 12 mutations and the level of HLA class I antigen in primary and metastatic tumours. Conclusions KRAS codon 12 mutations appear to be important in the downregulation of HLA class I antigen in NSCLC. Abnormal activation of the oncogenic KRAS pathway might provide a new treatment target for NSCLC.

Background Evidence is building steadily on the effectiveness of acupuncture therapy in pain relief and repeated acupuncture-induced pain relief is accompanied by improvement of hippocampal neural synaptic plasticity. To further test the cellular and molecular changes underlying analgesic effect of acupuncture, the global change of acupuncture associated protein profiles in the hippocampus under neuropathic pain condition was profiled. Methods The chronic constrictive injury (CCI) model was established by ligature of the unilateral sciatic nerve in adult Wistar rats. Rats were randomized into normal control (NC) group, CCI group, and CCI with electroacupuncture (EA) stimulation group. EA was applied to bilateral Zusanli (ST36) and Yanglingquan (GB34) in the EA group. Differentially expressed proteins in the hippocampus in the three groups were identified by two-dimensional gel electrophoresis and matrix-assisted laser desorption/ionization time of flight mass spectrometry. The functional clustering of the identified proteins was analyzed by Mascot software. Results After CCI, the thermal pain threshold of the affected hind footpad was decreased and was reversed gradually by 12 sessions of acupuncture treatment. Following EA, there were 19 hippocampal proteins identified with significant changes in expression (>2-fold), which are involved in metabolic, physiological, and cellular processes. The top three canonical pathways identified were “cysteine metabolism”, “valine, leucine, and isoleucine degradation” and “mitogen-activated protein kinase (MAPK) signaling”. Conclusions These data suggest that the analgesic effect of EA is mediated by regulation of hippocampal proteins related to amino acid metabolism and activation of the MAPK signaling pathway.

Cancer stage is critical for treatment planning and assessing disease prognosis. The percentage of unknown staged cancer cases varies considerably across state cancer registries; factors contributing to the variations in unknown stage have not been reported in the literature before. The purpose of this study was to examine whether these variations were influenced by demographic and/or clinical factors as well as the type of reporting facility.Invasive colorectal, lung, female breast, and prostate cancers diagnosed between 2004 and 2007 were obtained from the North American Association of Central Cancer Registries (NAACCR); 47 population-based cancer registries in the United States were included. The unknown stage was based on Summary Stage 2000 codes derived from Collaborative Stage Version 1 (CSv1). Relative importance analysis was used to identify variables that were essential in predicting unknown stage. Using state central registries as analytical units, multiple linear regression was used to evaluate factors associated with the percentage of unknown stage by cancer site; potential outlier registries with a high percentage of unknown stage cases were identified using boxplots and standardized residuals.Overall, lung cancer had the highest percentage of unknown stage (8.3%) and prostate cancer had the largest variation of unknown stage among registries (0.6%-18.1%). The percentages of neoplasms not otherwise specified (NOS) histology, non-microscopic confirmation, and non-hospital reporting source were positively associated (p less than 0.05) with percentage of unknown stage for all studied cancer sites before adjustment. Variables that retained a positive association with unknown stage including all demographic and clinical variables, year of diagnosis, and type of reporting source were black race, metropolitan area less than 1 million population, histologies of neoplasms NOS or epithelial neoplasms NOS, diagnosis year 2005, and non-hospital reporting source for colorectal cancer; metropolitan area less than 1 million population, neoplasms NOS histology, and non-hospital reporting source for female breast; and diagnosis year 2005 and non-hospital reporting source for prostate. After adjustment, none of the predictors were significant for lung cancer. We observed 1 potential outlier registry each for colorectal, lung and female breast cancers.Factors associated with unknown stage differ by cancer site; however, the type of reporting source is an important predictor of unknown stage for all cancers except lung after adjustment. Central registries with high percentage of unknown stage should be made aware of their data quality issue(s). As a result, these registries can investigate those factors and provide training to registrars to improve their cancer data quality.

Thyrotropin (TSH) is a protein that plays a key role in the control of thyroid function. TSH consists of a common α-subunit and a unique β-subunit; the latter is responsible for hormone specificity. A novel splice variant of human TSHβ was identified in 2009. To date, only the tissue distribution of the human TSHβ splice variant mRNA has been studied. Therefore, we aimed to characterize the protein translated from this splice variant. Salting-out, dialysis and concentration of serum proteins were followed by immunoprecipitation to identify the hTSHβ splice variant in serum. Stable CHO cell lines expressing the hTSHβ splice variant and V5-hTSHα were generated. After co-culture, co-immunoprecipitation was used to determine if the hTSHβ splice variant can dimerise with TSHα. We showed for the first time that the hTSHβ splice variant exists in human serum and dimerises with TSHα. To explore the relationship between the TSHβ splice variant and the pathogenesis of autoimmune thyroiditis, we assessed variations in the mRNA expression of the TSHβ splice variant in the peripheral blood leukocytes (PBLs) of Hashimoto's thyroiditis (HT) patients using quantitative RT-PCR. We found that the mRNA expression levels of the TSHβ splice variant were higher in the PBLs of HT patients who were not undergoing prednisone therapy (n = 10, P0.0001) and in the PBLs of HT patients with a longer duration of illness (18 months) who were undergoing prednisone therapy (n = 5, P = 0.023) than in those of the control group. This pattern was reversed in the PBLs of HT patients with a shorter duration of illness (9 months) who were undergoing prednisone therapy (n = 8, P0.0001). Dexamethasone inhibition of the TSHβ splice variant mRNA expression occurred in a dose- and time-dependent manner. These results demonstrated that the TSHβ splice variant may participate in the pathogenesis of HT.

The purpose of the present study was to investigate the risk factors associated with lymph node metastatic recurrence in patients with N0 esophageal cancer after Ivor-Lewis esophagectomy based on the detection of Mucin 1 mRNA and vascular endothelial growth factor (VEGF) C mRNA. The subjects were 82 patients with pN0 esophageal cancer who underwent Ivor-Lewis esophagectomy with two-field lymph node dissection from January 2001 to January 2005. A total of 501 lymph nodes obtained from these patients were re-evaluated by reverse transcriptase-polymerase chain reaction (RT-PCR) to detect mucin l (MUC1) mRNA; VEGF-C mRNA was also detected in esophageal cancer issues by RT-PCR .The diagnosis of lymph node micrometastasis (LNMM) was based on the detection of MUC1 mRNA. The Kaplan–Meier method was used to calculate the survival rate and lymph nodal metastatic rate, the log-rank test was performed to compare the recurrence rate, and Cox regression multivariate analysis was performed to determine independent prognostic factors. MUC1 mRNA was detected in 29 lymph nodes from 23 patients, which accounted for 5.79% of all the 501 lymph nodes and 28.05% of all 82 patients, respectively. Vascular endothelial growth factor C mRNA was identified in esophageal cancer issues from 42 (51.22%) patients. The overall 3- and 5-year survival rates of 82 patients were 78.0 and 51.2%, respectively. First recurrence exhibiting lymph nodal metastasis was recognized in 37 patients (45.1%) in the first 3 years after operation. The lymph node metastatic rate in patients in the first 3 years after operation was significantly associated with T status (p

This study was conducted to determine the results obtained with laparoscopic cholecystectomy (LC) at the Department of the First Minimal Invasive Surgery and Bile Duct Surgery, Sheng Jing Hospital of China Medical University. The authors compared current six years results with those at the former six years of the experience and developing a guideline.Between May 1997 and May 2009, 2400 LCs were performed at the "Department of the First Minimal Invasive Surgery and Bile Duct Surgery, Sheng Jing Hospital of China Medical University"; 952 patients were operated on between May 1997 and May 2003, and 1,448 between Jun 2003 and May 2009. Data describing the peri-operative interventions, operative methods and maneuvers, complications and methods of preventing them was collected and analyzed.Mean hospital stay was 3.75 days. Conversion to open surgery was required for 0.46% of cases (11 patients). The surgical complication rate was 0.66%, with the most frequent being bile duct complications (0.42%) and bleeding (0.08%). Two patients died (0.08%). When the results (1997-2003 vs. 2003-2009) were compared, the differences in the history of a previous operation (30 vs. 23.8%, p = 0.001), role of the resident in LC (4.4 vs. 28.2%, p0.001), number of LCs for chronic calculous cholecystitis (52.42 vs. 66.16%, p0.001), for acute calculous cholecystitis (13.76 vs. 6.5%, p0.001) and for gallbladder polyp (32.76 vs. 26.45%, p = 0.001) and mean hospital stay (4.65 vs. 2.85 days, p = 0.034) was observed. In the latter 1448 cases (60.3%), LC was done without the need for routine urinary catheter or gastric tube insertion.These results should be interpreted with caution as this is a retrospective study with much uncontrolled bias. We can rely on our practice to accumulate and summarize our experience to formulate perioperative interventions, gradually develop routines management protocols and shorten the learning curve.

To explore the mechanism of electroacupuncture (EA)-induced cumulative analgesic effects on chronic pain in rats with or without ovariectomy (OVX).A total of 110 female Wistar rats were randomized into normal control (n=10), chronic constrictive injury (CCI, n=10), CCI+EA (n=30), OVX+CCI (n=30), and OVX+CCI+EA (n=30) groups. Each of the latter 3 groups was further divided into 2 days (2 d), 2 weeks (2 W) and 3 weeks (3 W) subgroups, respectively (n=10 in each subgroup). The CCI pain model was established by ligature of the right sciatic nerve, and the memory impairment model duplicated by OVX. The paw withdrawal latency (PWL, pain threshold) of the bilateral footplates was detected by radiant heat irradiation, and the bilateral difference in PWL (PWLD) was used to evaluate changes in the pain reaction. Morris water maze test was conducted for evaluating the rats' learning-memory ability. EA was applied to bilateral Zusanli (ST36) and Yanglingquan (GB34) for 2 d, 2 W and 3 W, respectively. Pituitary and hypothalamic beta-endorphin (EP) and adrenocorticotrophic hormone (ACTH) contents were detected by immunoradioassay.Compared with the CCI group, PWLD of the CCI+EA-3 W group decreased significantly (P0.05). Compared with the OVX+CCI group, PWLD of the OVX+CCI+EA-3 W group was lowered considerably (P0.05), but the value was markedly higher than its basal value and those of the normal control and CCI+EA groups (P0.05). In comparison with the sham-OVX group, the escape latency, swimming distance (SD) in the target quadrant and total SD were increased remarkably in the OVX group (P0.05), while the number of target platform crossings was decreased significantly (P0.05), suggesting an impairment of the OVX rats' learning-memory ability. In simple CCI rats, both beta-EP and ACTH contents of the pituitary increased markedly (P0.05), and those of the hypothalamus decreased obviously compared to the normal control group (P0.05). After EA, pituitary and hypothalamic ACTH levels were significantly lowered at 2 d and hypothalamic ACTH and beta-EP contents increased obviously at 3 W in comparison with the CCI group (P0.05). In OVX+CCI rats, following EA, pituitary beta-EP contents at 2 d, 2 W and 3 W, and hypothalamic beta-EP and ACTH contents at 2 W and hypothalamic ACTH levels at 3 W increased significantly (P0.05), but hypothalamic beta-EP level at 3W decreased markedly (P0.05). The effects of repeated EA in lowering pituitary ACTH and raising hypothalamic beta-EP and ACTH levels disappeared after OVX+CCI.Repeated EA has a cumulative analgesic effect, which is closely associated with its effects in regulating pituitary and hypothalamic beta-EP and ACTH levels. OVX may weaken the analgesic effect of EA by affecting hypothalamic-pituitary axis activity.

To investigate the potential toxicity of the vehicle used for triamcinolone acetonide (TA) to the cornea, lens, ciliary body, and retina of pigmented rabbits.Forty chinchilla rabbits (40 eyes) were divided into four groups: group A (control group) eyes received an intravitreal injection of 0.1 ml sterile saline solution; group B eyes received 0.1 ml (1.3 mg) TA plus vehicle; group C eyes received 0.1 ml (1.3 mg) TA alone (vehicle eliminated); group D eyes received 0.1 ml vehicle only. Intraocular pressure (IOP) was measured pre-injection and at 1, 7, 14, 30, and 90 days post-injection. Scotopic and photopic electroretinograms (ERG) were examined pre-injection and 7, 30, and 90 days post-injection. Animals were sacrificed 7, 30, and 90 days post-injection. Eyes were enucleated and examined by light microscopy (LM) and electron microscopy (EM).The IOP of groups B and C was higher than that of other groups on days 1, 7, and 14 post-injection (p0.05). ERG amplitudes of groups B and D were lower than those of other groups on days 7 and 30 post-injection (p0.05). Histopathological sections indicated morphologic changes in the ciliary body, lens, and retina of eyes in groups B and D.Vehicle used for TA is toxic to the lens, ciliary body, and retina of pigmented rabbit eyes after injection of intravitreal TA.

To investigate and evaluate the clinical features, diagnostic methods, surgical management of trachea tumors in order to improve patients outcome.Clinical data of 32 patients with trachea tumors surgically treated from June 1986 to June 2005 were retrospectively analyzed. There were 22 male and 10 female patients. The age ranged from 14 to 63 years old with a median of 48 years old. The surgical procedures performed were resection and reconstruction of trachea in 10 cases, right or left pneumonectomy and carinal resection and reconstruction in 8 cases, right sleeve upper lobectomy, carinal resection and reconstruction of trachea and carina in 8 cases, and carina resection and reconstruction with tumor removal through tracheal windows 6 cases. The tracheal defect was repaired with a Teflon flap in two patients. Cardiopulmonary bypass was used in 2 patients during surgery.The histological examination of resected lesions revealed squamous cell carcinoma in 19 cases, adenoid cystic carcinoma in 8 cases, adenocarcinoma in 2 cases, carcinoid in 2 cases, leiomyosarcoma in 1 case and adenoma in 1 case. One case had infection of thoracic cavity and 3 cases experienced temporary cardiac arrhythmia. There was no operative death. The follow-up periods were from 5 months to 3 years. The 1, 2 and 3 year survival rates were 93.7%, 59.4% and 50.0% respectively.Squamous cell carcinoma adenoid cystic carcinoma are the most common in trachea tumors. Preoperative bronchoscope examination and chest CT scan can provide valuable diagnostic data. Proper choice of surgical procedure is important for improved patients' outcome.

Objective: Mediastinal lymph node metastasis (N2) is a key prognostic factor for lung carcinoma. This study was undertaken to investigate the relationshipbetweenvascularendothelial growthfactorC (VEGF-C)expressionandpostoperativeearly recurrence in patientswith N2 non-smallcell lung cancer. Methods: Cancer tissue samples from 92 patients with pN2 non-small-cell lung cancer and benign lung disease tissues samples from 30 patients were examined by reverse transcription polymerase chain reaction (RT-PCR) and immunohistochemistry assays to detect VEGF-C expression. The difference of VEGF-C expression was compared by x 2 test. All patients with N2 disease were evaluated within 1 year after surgery to detect early tumour recurrence. Cox regression analysis was performed to determine the risk factors of postoperative early recurrence of N2 lung cancer. Results: VEGF-C mRNA expression was observed in 64 (70%) pN2 lung cancer tissues, but was not found in benign lung disease tissues. Early recurrence occurred in 43 patients (47%) at 1 year after operation. The main pattern was distant recurrence, and the most frequent sites were the brain and lung. The early recurrence rate in patients with positive VEGF-C expression was significantly higher than that of those with negative VEGF-C expression (P = 0.006, log-rank test). Cox regression analysis revealed that positive VEGF-C expression in tumours (hazard ratio (HR) = 2.523, P = 0.037) was an independent risk factor of postoperative early recurrence of N2 lung cancer. Conclusions: VEGF-C expression was high in N2 lung cancer, with significant correlation to postoperative early recurrence. About one-half of the patients with N2 non-small-cell lung cancer would develop recurrence disease within 1 year after surgery, frequently with mediastinal nodes, brain or lung metastases. VEGF-C might be a predictor of postoperative early recurrence in patients with N2 non-small-cell lung cancer. # 2009 European Association for Cardio-Thoracic Surgery. Published by Elsevier B.V. All rights reserved.

To investigate the patterns of abdominal lymph node metastasis in patients with the middle thoracic esophageal squamous cell carcinoma and to evaluate the prognostic factors.Three hundred and sixty-eight patients with the middle thoracic esophageal squamous cell carcinoma from January 1998 to January 2003 were reviewed. There were 289 male and 79 female patients. The age ranged from 38 to 79 years, with a mean of 56 years. Preoperative clinical stage was stage I to III, and all patients underwent Ivor-Lewis esophagectomy with two-field lymphadenectomy. Follow-up was completed for all patients with a mean time of 68 months. Survival rate was calculated by Kaplan-Meier method. COX regression analysis was performed to identify risk prognostic factors.Abdominal lymph node metastasis occurred in 58 (15.8%) patients, with 36.2% (21/58) of them being in stage T1 or T2. Skipping abdominal lymph node metastasis was recognized in 13.8% (8/58) patients, with all of them being in stage T1 or T2. The overall 5-year survival rate of patients with abdominal lymph node metastasis (10.3%) was lower than that of those with thoracic lymph node metastasis (18.3%). The prognosis of patients with distant abdominal lymph node metastasis was bad, and nobody could survive over 5 years.COX analysis showed that 5 or more positive nodes and distant abdominal node metastasis were independent risk factors of patients with abdominal lymph node metastasis.Abdominal lymph node metastasis in patients with the middle thoracic esophageal squamous cell carcinoma occurs frequently, and the surgery favorable for extensive abdominal lymph node dissection should be selected. The prognosis of patients with abdominal lymph node metastasis is poor, especially those with more positive nodes and distant abdominal node metastasis.

To investigate the local control of radiotherapy following Ivor-Lewis esophagectomy in the patients with stage IIA middle-third thoracic esophageal cancer.From June 1999 to June 2002, 125 patients with stage IIA squamous cell carcinoma of the middle-third thoracic esophagus were treated with Ivor-Lewis esophagectomy with two-fields lymphadenectomy. The survival rate was calculated by Kaplan-meier method and the difference of recurrence rate compared by chi(2) test.The 3-year and 5-year survival rates were 58.4% and 43.2% in this group, respectively. Tumor recurrence occurred in 61 of the 125 patients (48.8%) within 3 years after operation. Of all cases of recurrence, 38 patients (30.4%) developed locoregional recurrence (including 5 patients with locoregional and hematogenous recurrence simultaneously). The locoregional recurrence rate of patients who received postoperative radiotherapy (20.3%) was significantly lower than that of both the group who received adjunctive chemotherapy (40.6%) and the group without adjunctive therapy (41.4%) (P0.05).About half of the patients would develop recurrence disease within 3 years after Ivor-Lewis esophagectomy with two-fields lymph-adenectomy. Radiotherapy following Ivor-Lewis esophagectomy is an effective strategy to control local recurrence of the stage II A middle-third thoracic esophageal cancer.

Even if complete resection was performed, some patients with esophageal carcinoma still develop tumor recurrence. This study was undertaken to evaluate the effectiveness of adjuvant radiotherapy after modified Ivor-Lewis esophagectomy on preventing lymph node recurrence of the mid-thoracic esophageal carcinoma.Three hundred sixty-six patients with mid-thoracic esophageal squamous cell carcinoma who underwent modified Ivor-Lewis esophagectomy between June 1999 and June 2004 were retrospectively reviewed. All patients were followed up within 3 years after surgery to detect lymph node recurrence. The Kaplan-Meier method was used to calculate the recurrence rate, and Cox regression analysis was performed to identify risk factors of lymph node recurrence.The overall 3-year and 5-year survival rates in all patients were 57.9% and 43.7%, respectively. Lymph node recurrence occurred in 105 patients (28.7%) within 3 years after surgery. The lymph node recurrence rate of patients with postoperative adjuvant radiotherapy was significantly lower than that of those with adjuvant chemotherapy (p = 0.03) and those without adjuvant therapy (p0.01). Cox regression analysis showed that T stage, N status, and postoperative adjuvant radiotherapy were independent relevant factors for lymph node recurrence.Postoperative adjuvant radiotherapy after modified Ivor-Lewis esophagectomy might prevent lymph node recurrence of mid-thoracic esophageal carcinoma.

To observe the accumulative analgesic effect of electroacupuncture (EA) and the simultaneous changes of protein kinase A (PKA) expression in hypothalamus and hippocampus in rats with chronic constrictive injury (CCI) or/and learning-memory impairment.Sixty-eight female Wistar rats were randomized into normal control, CCI, CCI + EA 2 d, CCI + EA 2 w, OVX + CCI, OVX + CCI + EA 2 d and OVX + CCI + EA 2 w groups, with 10 cases in each except OVX + CCI group (n=8). CCI pain model was established by ligature of the right sciatic nerve with surgical suture. EA (2/15 Hz, 1-2 mA, 30 min) was daily applied to bilateral "Zusanli" (ST 36) and "Yanglingquan" (GB 34) for 2 days (2 d) and 2 weeks (2 w) respectively. Neuro-memory impairment was induced by OVX plus subcutaneous injection of D-galactose. Hyperalgesic scores (HS) were detected with radiation-heat irradiation and PKA activity was detected by immunohistochemical method.After CCI, HS of all groups increased significantly in comparison with normal control group (P0.05). In simple CCI rats, compared with CCI group, HS of both CCI + EA 2 d and CCI + EA 2 w groups decreased markedly (P0.05), and that of CCI + EA 2 w group was evidently lower than that of CCI + EA 2 d group on the 18th day after CCI (P0.05). In memory impairment rats, HS of both OVX + CCI + EA 2 d and OVX + CCI + EA 2 w groups was significantly lower than that of OVX+ CCI group (P0.05); and no significant difference was found between OVX + CCI + EA 2 w and OVX + CCI + EA 2 d groups in HS (P0.05). Results of immunohistochemistry showed that the integral grey values (IGV) of PKA of paraventricular nucleus (PVN), arcuate nucleus (ARC) and supraoptic nucleus (SON) of hypothalamus in CCI + EA 2 w group were significantly lower than those in normal control and CCI + EA 2 d groups (P0.05). IGV of PVN and SON in OVX + CCI + EA 2 w group were also markedly lower than those in OVX + CCI group (P0.05), displaying upregulation and cumulative increase of PKA expression by EA 2 w. IGV of PKA, ARC and SON in OVX + CCI + EA 2 w group were markedly higher than those in CCI + EA 2 w group (P0.05), suggesting an apparent attenuation of the cumulative upregulation effect of PKA expression after learning-memory injury. The changing tendency of PKA expression in hippocampal CA1 region was similar to that of SON after repeated EA of ST36 and GB34.Repeated EA has a cumulative analgesic effect in CCI rats, which is probably related to its resultant upregulation of PKA expression in neurons of hypothalamus and hippocampus and the animals' neuro-memory.

Objective: To control the postoperative local recurrence is one of the critical factors to improve prognosis of patients with esophageal carcinoma. The aim of this study is to evaluate the effectiveness of modified Ivor-Lewis esophagectomy plus adjuvant radiotherapy for local control of stage IIA squamous cell carcinoma in the mid-thoracic esophagus. Methods: One hundred and twenty-five patients with stage IIA midthoracic esophageal squamous cell carcinoma who underwent modified Ivor-Lewis esophagectomy between June 1999 and June 2002 were included in the retrospective analysis. All the patients were evaluated within 3 years after surgery to detect tumor recurrence. Kaplan—Meier method was used to calculate the survival rate and logistic regression analysis was performed to identify risk factors of locoregional recurrence. Results: The overall 3-year and 5-year survival rate in all patients was 58.4% and 43.2%, respectively. Tumor recurrence occurred in 61 patients (48.8%) within 3 years after operation. The median disease-free interval was 12.6 months. Thirty-three patients (26.4%) developed locoregional recurrence, 23 patients (18.4%) developed distant recurrence and 5 patients (4.0%) developed locoregional and distant recurrence simultaneously. Locoregional recurrence rate of patients with postoperative radiotherapy was significantly lower than that of those without postoperative radiotherapy (p < 0.05). Logistic regression analysis showed that adjuvant radiotherapy (p = 0.007) was an independent risk factor for tumor locoregional recurrence. Cox regression analysis showed that locoregional recurrence but not adjuvant radiotherapy was a relevant prognostic factor of patients with stage IIA esophageal cancer. Conclusions: Modified Ivor-Lewis esophagectomy with two-field lymph node dissection plus adjuvant radiotherapy might be an effective strategy to achieve local control of stage IIA mid-thoracic esophageal squamous cell carcinoma.

The purpose of the present study was to investigate the prevalence of lymph node micrometastasis (LNMM) based on the detection of MUC1 mRNA, and assess the impact of these micrometastases on prognosis after resection of pathologic N0 (pN0) non-small cell lung cancer (NSCLC).The subjects were 89 patients who underwent complete resection of pN0 NSCLC at our department between January 2000 and January 2002. All lymph nodes (402 stations) obtained from these patients were re-evaluated by reverse transcriptase-polymerase chain reaction (RT-PCR) to detect MUC1 mRNA. The diagnosis of LNMM was based on the detection of MUC1 mRNA. The Kaplan-Meier method was used to calculate the survival rate, and Cox regression multivariate analysis was performed to determine independent prognostic factors.Micrometastases were detected in 36 lymph node stations (9.0%) from 21 patients (23.6%). The TNM staging of these 21 patients was upregulated from stage IA-IIB to stage IIIA. The 5-year survival rate of patients with LNMM was significantly lower than that of patients without LNMM (23.8% versus 44.1%; p0.05). The results of multivariate analysis confirmed that T status, histology, and LNMM were independent prognostic factors.The prevalence of LNMM in patients with pN0 NSCLC was 23.6% (21/89). T status, histology, and LNMM were independent prognostic factors.

To observe the regularity of electroacupuncture (EA) analgesia and to analyze its relation to hypothalamus-pituitary-adrenal cortex axis function in chronic constrictive injury (CCI) and ovariectomy (OVX) rats.A total of 110 Wistar rats anesthetized with mixture solution of 1.5% chloralose (50 mg/kg) and 25% urethrane (420 mg/kg, i.p.) were randomized into control (n=10), CCI (n =10), CCI + EA (n=30), OVX + CCI (n=30), OVX + CCI + EA (n=30) groups, and the later 3 groups were further divided into 2 times (2 t), 2 weeks (2 w) and 3 w time courses, with 10 cases in each. Forty-five days after OVX, Morris water maze test was conducted to evaluate the OVX rats' memory-learning ability. Chronic pain model was established by ligating the right sciatic nerve with a piece of suture. EA (2/15 Hz, 1 mA) was applied to bilateral "Zusanli" (ST 36)-"Yanglingquan" (GB 34) for 30 min, once daily for 2 t, 2 w, 3 w respectively. The paw withdrawal latency (PWL) was detected to be used as the pain threshold. Under deep anesthesia, the rat was decapitated for collecting blood samples. Plasma adrenocorticotropic hormone (ACTH), beta-endorphine (EP), cortisone (COR) contents were detected using radioimmunoassay.In comparison with control group, PWL difference values (PWLDV) of CCI + EA, OVX + CCI and OVX + CCI + EA groups increased significantly (P0.05), suggesting a marked decrease of pain threshold. Compared with CCI group, PWLDV of CCI + EA group at 3 w decreased significantly (P0.05), being close to normal control group (P0.05). Compared with OVX + CCI group, PWLDV of OVX + CCI + EA at 2 w and 3 w lowered significantly (P0.05), suggesting an evident pain relief. In comparison with CCI + EA group, PWLDV of OVX + CCI + EA group at most time courses were considerably higher (P0.05), showing a better cumulative analgesic effect in CCI rats without OVX. In CCI group, plasma beta-EP increased slightly, ACTH had no clear changes, and COR lowered lightly at 2 t. No significant differences were found between control and CCI + EA groups in beta-EP and ACTH levels at 2 w and 3 w (P0.05), only COR levels of CCI + EA group at 2 w and 3 w increased significantly (P0.05). Compared with control group, beta-EP levels of OVX + CCI group at 2 w and 3 w increased significantly (P0.05); plasma ACTH had no marked changes (P0.05); COR contents of OVX + CCI group decreased evidently at 2 t and increased markedly at 2 w (P0.05). Compared with OVX + CCI group, in OVX + CCI + EA group, beta-EP levels of 2 t and 2 w decreased significantly (P0.05); ACTH levels increased evidently at 2 t and 3 w, and decreased markedly at 2 w (P0.05); and COR level at 2 w decreased significantly (P0.05). It indicated that when cumulative EA analgesia appeared, in CCI animals, only plasma COR level increased pronouncedly, while in OVX + CCI rats, both plasma beta-EP and COR contents decreased evidently.Both plasma beta-EP and COR are involved in the accumulative analgesic effect of EA in the rat, and decline of learning memory ability may weaken the analgesic effect of EA to a certain degree, but no clear correlation tendency is found between changes of plasma beta-EP and COR and the improvement of pain behavior.

Despite increasingly radical surgery for esophageal carcinoma, many patients still develop tumor recurrence after operation. This study was designed to evaluate the recurrence pattern of squamous cell carcinoma in the middle thoracic esophagus after modified Ivor-Lewis esophagectomy.We retrospectively reviewed data of 196 patients who underwent modified Ivor-Lewis esophagectomy with two-field lymph node dissection from January 1997 to January 2001. Recurrence was classified as locoregional or hematogenous recurrence. Logistic regression analysis was performed to identify risk factors of postoperative recurrence.The overall 3-year and 5-year survival rates in all patients were 53% and 31%, respectively. Recurrence was recognized in 96 patients (48.9%) in the 3 years after operation. The median time to tumor recurrence was 12.2 months. The pattern of recurrence was locoregional in 52 patients (mainly mediastinal in 41, single cervical/supraclavicular in 8), hematogenous in 44 patients (simultaneous locoregional and hematogenous in 10; mainly liver, bone, or lung in 39). The locoregional recurrence rate was significantly lower in patients with postoperative radiotherapy than that in patients without postoperative radiotherapy (p = 0.02). Logistic regression analysis showed that T3 (p = 0.032), N1 (p = 0.003), and postoperative radiotherapy (p = 0.022) were independent risk factors for tumor locoregional recurrence.About one half of the patients would develop recurrent disease within 3 years after modified Ivor-Lewis esophagectomy with two-field lymph node dissection, and most of them had mediastinal lymph node, liver, bone, or lung metastasis. Postoperative radiotherapy was beneficial in the control of locoregional recurrence.

Early postoperative relapse in esophageal cancer might be related to occult lymph node micrometastasis that could not be detected by routine histopathologic examination. This study was to investigate the clinical significance of detecting Mucin 1 (MUC1) mRNA in diagnosing occult lymph node micrometastasis in esophageal cancer patients, and to evaluate its prognostic significance.The expression of MUC1 mRNA in 366 regional lymph nodes from 63 esophageal squamous cell cancer (ESCC) patients without histopathologically confirmed invasion (pN0), 30 paraesophageal lymph nodes from patients with benign esophageal diseases, and 15 lymph nodes and 15 tumor tissues from ESCC patients with histopathologically proved metastasis (pN1) were detected by reverse transcription-polymerase chain reaction (RT-PCR) to determine micrometastasis. Survival difference was compared by Chi(2) test. Logistic regression analysis was performed to assess independent prognostic factors.Specificity of genetic diagnosis was 100.0% (30/30) for occult lymph node micrometastasis, and 90.0% (27/30) for lymph node micrometastasis. MUC1 mRNA was identified in 30 (8.2%) lymph nodes from 22 (34.9%) patients. Occult lymph node micrometastasis was diagnosed in these patients. The 3-year survival rate was significantly lower in the patients with lymph node micrometastasis than in the patients without lymph node micrometastasis (54.5% vs. 80.5%, P0.01). In Logistic regression analysis, lymph node micrometastasis (P0.05, odds ratio=3.71) and T3 tumor (P0.05, odds ratio=7.17) were independent prognostic factors.It is helpful to diagnose occult lymph node micrometastasis by detecting the expression of MUC1 mRNA in lymph nodes of pN0 ESCC patients. Lymph node micrometastasis may predict poor prognosis of the patients after radial operation.

About one half of the patients with esophageal cancer may recur within 3 years after operation, but the recurrence pattern is still unclear. This study was to investigate the recurrence patterns of esophageal cancer after Ivor-Lewis esophagectomy.Clinical data of 196 patients with squamous cell carcinoma of the middle third thoracic esophagus, who underwent Ivor-Lewis esophagectomy with two-field lymph node dissection from Jan. 1997 through Jan. 2001, were reviewed. The risk factors of postoperative recurrence within 3 years were analyzed with Logistic regressive model.Recurrence was recognized in 96 (48.9%) patients within 3 year after operation. The median time to recurrence was 12.2 months. Of the 96 cases of recurrence, 52 (54.1%) were locoregional, including 41 cases (78.8%) of mediastinal lymph node metastasis, and 8 cases (15.3%) of single cervical lymph node metastasis; 44 (45.8%) were hematogenous, including 10 cases of locoregional-hematogenous recurrence, and mainly located at liver, bone, and lung (39, 88.6%). The locoregional recurrence rate was significantly lower in the patients who received postoperative radiotherapy than in the patients have not received postoperative radiotherapy (23.3% vs. 41.3%, P0.05). Logistic analysis showed that T3 and N1 tumor were independent risk factors of postoperative tumor recurrence.About one half of the patients would develop recurrent disease within 3 years after Ivor-Lewis esophagectomy, and most of them were with mediastinal lymph node, liver, bone, or lung metastasis. Postoperative radiotherapy is helpful to control locoregional recurrence.

To explore the correlation between early postoperative tumor relapse with lymph node micrometastasis in the patients with pN(0) esophageal cancer.Using reverse transcriptase-polymerase chain reaction (RT-PCR), one hundred and sixty-six regional lymph nodes obtained from forty-three patients with esophagus cancer without invasion of the tumor confirmed by histopathologic analysis (pN(0)) were studied for further detecting mRNA of Mucin1 (MUC1) gene and determining nodal micrometastasis. All the patients underwent radical resection and regional lymph node dissection. Patients were followed up for one year to detect early tumor relapse. Difference in relapse was compared by chi(2) test.MUC1 mRNA expression was identified for twenty-six lymph nodes (15.7%), in eighteen patients (42%) who were diagnosed as having nodal micrometastasis. TNM staging for these patients was up-regulated from stages I-II(A) to stages II(B)-III. Relapse disease was found in nine patients with lymph nodes micrometastasis and three patients without nodal micrometastasis (P0.05).Early tumor relapse after radical surgery in the patients with pN(0) esophageal cancer might be correlated with nodal micrometastasis.

Occult micrometastasis to mediastinal lymph node, which could not be detected by routinely histopathologic examination, might be correlated with the prognosis of patients with non-small cell lung carcinoma (NSCLC). The aim of this stud y was to diagnose occult micrometastasis of mediastinal lymph node in NSCLC patients and evaluate its prognostic significance.Using reverse transcription-polymerase chain reaction (RT-PCR), 242 stations of mediastinal lymph nodes, which were free of tumor determined by histopathologic examination(pN0), from 58 patients were examined for MUC1 gene mRNA and to diagnose occult micrometastasis. All the patients were followed-up for three years. The survival rate was calculated by Kaplan-Meier method and the survival was compared with log-rank test between the patients with and without occult nodal micrometastasis.The MUC1 gene mRNA was identified in 23 stations of lymph nodes from 16 patients, and nodal occult micrometastasis was diagnosed in the 27.6% of the patients. TNM staging for these patients was up-regulated from stageI(A)-II(B) to stage III(A). The 3-year survival rate in the patients with nodal occult micrometastasis (43.7%) was lower than that in the patients without nodal occult micrometastasis (73.8%) (P0.05).The expression of MUC1 gene mRNA in mediastinal lymph node is associated with poor prognosis of NSCLC patients with pN0 disease, suggesting that it may be an indicator of poor prognosis.

BACKGROUND:Mutations in OTOF and PJVK genes cause DFNB9 and DFNB59 types of hearing loss, respectively. The patients carrying pathogenic mutations in either of these genes may show the typical phenotype of auditory neuropathy spectrum disorder (ANSD). The aim of the present study was to identify OTOF and PJVK mutations in sporadic ANSD patients. METHODS AND FINDINGS:A total of 76 unrelated Chinese non-syndromic ANSD patients were sequenced on the gene OTOF and PJVK exon by exon. Variants were valued in 105 controls with normal hearing to verify the carrying rate. We identified one pathogenic mutation (c.1194T>A) and three novel, possibly pathogenic, variants (c.3570+2T>C, c.4023+1 G>A, and c.1102G>A) in the OTOF gene, and one novel, possibly pathogenic, variant (c.548G>A) in PJVK. Moreover, we found three novel missense mutations within the exons of OTOF. CONCLUSIONS:As we identified 4 and 1 possible pathogenic variants of the OTOF gene and the PJVK gene, respectively, we believe that screening in these genes are important in sporadic ANSD patients. The pathogenicity of these novel mutations needs further study because of their single heterozygous nature. Knowledge on the mutation spectra of these genes in Chinese would be beneficial in understanding the genetic character of this worldwide disease.