Impact and effect of preoperative short-term preoperative pulmonary-related training on patients with gastric cancer: a randomized controlled single center trial.

PURPOSE: This study aimed is to evaluate the impact of pre- and postoperative pulmonary-related training, including respiratory and aerobic training, on postoperative pulmonary complications (PPCs) after radical resection of gastric cancer (GC). METHODS: We conducted a randomized controlled trial of 121 participants who received a systematic, comprehensive, high-intensity pulmonary exercise regimen for 5 days preoperatively and at least 5 days postoperatively. The control group received standard preoperative care. We analyzed the occurrence of PPCs in both groups as the primary outcome RESULTS: A total of 43 of 121 participants (35.5%) were diagnosed as having PPCs, and the incidence of PPCs was markedly lower in the training group than in the control group (26.2% [16 of 61] vs 45.0% [27 of 60]; P = .031). Moreover, the duration of the postoperative hospital stay was shorter in the training group (8.69 ± 1.92 days) than the control group (9.57 ± 2.16 days; P = .020) and reduced hospitalization costs, amounting to €9605.1 ± €2556.26 in the training group and €10,594.6 ± €2560.7 in the control group (P = .035). CONCLUSION: Our study established that a perioperative pulmonary-related training notably diminishes the incidence of PPCs, curtails the duration of hospitalization, and mitigates hospitalization expenses for patients undergoing GC surgery.

Consolidation chemotherapy after definitive concurrent chemoradiotherapy in patients with inoperable esophageal squamous cell carcinoma: a multicenter non-inferiority phase III randomized clinical trial.

BACKGROUND: Definitive concurrent chemoradiotherapy (dCCRT) is the gold standard for the treatment of locally advanced esophageal squamous cell carcinoma (ESCC). However, the potential benefits of consolidation chemotherapy after dCCRT in patients with esophageal cancer remain debatable. Prospective randomized controlled trials comparing the outcomes of dCCRT with or without consolidation chemotherapy in patients with ESCC are lacking. In this study, we aim to generate evidence regarding consolidation chemotherapy efficacy in patients with locally advanced, inoperable ESCC. METHODS: This is a multicenter, prospective, open-label, phase-III randomized controlled trial comparing non-inferiority of dCCRT alone to consolidation chemotherapy following dCCRT. In total, 600 patients will be enrolled and randomly assigned in a 1:1 ratio to receive either consolidation chemotherapy after dCCRT (Arm A) or dCCRT alone (Arm B). Overall survival will be the primary endpoint, whereas progression-free survival, locoregional progression-free survival, distant metastasis-free survival, and treatment-related toxicity will be the secondary endpoints. DISCUSSION: This study aid in further understanding the effects of consolidation chemotherapy after dCCRT in patients with locally advanced, inoperable ESCC. TRIAL REGISTRATION: ChiCTR1800017646.

Ionizing radiation induces vascular smooth muscle cell senescence through activating NF-κB/CTCF/p16 pathway.

Radiation injury of blood vessels (RIBV) is a serious long-term complication of radiotherapy, characterized by the development of atherosclerosis. The involvement of vascular smooth muscle cells (VSMCs) senescence in the pathogenesis of radiation-induced atherosclerosis has been implicated, yet the precise mechanisms governing VSMCs senescence remain inadequately comprehended. In this study, the senescence of VSMCs was examined by employing SA-ß-gal staining and assessing the expression of p16 and p21, both in vivo and in vitro. Our findings revealed that ionizing radiation (IR) has the potential to augment cellular senescence. In addition, IR significantly activated the NF-κB pathway, as evidenced by increased p65 nuclear translocation, phospho-p65 expression, and enhanced binding ability of p65 (EMSA). Furthermore, a decrease in HMGB2 expression following exposure to IR was observed via Western blot analysis, while CTCF expression remained unchanged. Interestingly, the formation of CTCF spatial clustering was detected under super-resolution fluorescence microscopy. Concurrently, the ChIP technique identified the facilitation of the interaction between CTCF and p16 gene through IR. The inhibition of CTCF or the overexpression of HMGB2 through lentiviruses effectively eliminates the formation of CTCF clusters and the upregulation of p16 and p21 after IR. Inhibition of NF-κB activation induced by IR by PDTC (100 µM) led to a decrease in the staining of SA-ß-gal, a reduction in p16 expression, an increase in HMGB2 protein expression and a decrease in CTCF clusters formation. This study provided significant insights into the role and mechanism of IR in VSMCs senescence by regulating NF-κB/CTCF/p16 pathway.

New scoring system combining computed tomography body composition analysis and inflammatory-nutritional indicators to predict postoperative complications in stage II-III colon cancer.

BACKGROUND AND AIM: Postoperative complications are important clinical outcomes for colon cancer patients. This study aimed to investigate the predictive value of inflammatory-nutritional indicators combined with computed tomography body composition on postoperative complications in patients with stage II-III colon cancer. METHODS: We retrospectively collected data from patients with stage II-III colon cancer admitted to our hospital from 2017 to 2021, including 198 patients in the training cohort and 50 patients in the validation cohort. Inflammatory-nutritional indicators and body composition were included in the univariate and multivariate analyses. Binary regression was used to develop a nomogram and evaluate its predictive value. RESULTS: In the multivariate analysis, the monocyte-lymphocyte ratio (MLR), systemic immune-inflammation index (SII), nutritional risk score (NRS), skeletal muscle index (SMI), and visceral fat index (VFI) were independent risk factors for postoperative complications of stage II-III colon cancer. In the training cohort, the area under the receiver operating characteristic curve of the predictive model was 0.825 (95% confidence interval [CI] 0.764-0.886). In the validation cohort, it was 0.901 (95% CI 0.816-0.986). The calibration curve showed that the prediction results were in good agreement with the observational results. Decision curve analysis showed that colon cancer patients could benefit from the predictive model. CONCLUSIONS: A nomogram combining MLR, SII, NRS, SMI, and VFI with good accuracy and reliability in predicting postoperative complications in patients with stage II-III colon cancer was established, which can help guide treatment decisions.

Combined Effect of TID Radiation and Electrical Stress on NMOSFETs.

The combined effect of total ionizing dose (TID) and electrical stress is investigated on NMOSFETs. For devices bearing both radiation and electrical stress, the threshold voltage shift is smaller than those only bearing electrical stress, indicating that the combined effect alleviates the degradation of the devices. The H bond is broken during the radiation process, which reduces the participation of H atoms in the later stage of electrical stress, thereby reducing the degradation caused by electrical stress. The positive charges of the oxide layer generated by radiation neutralize part of the tunneling electrons caused by electrical stress, and consume some of the electrons that react with the H bond, resulting in weaker degradation. In addition, the positive charges in shallow trench isolation (STI) generated by radiation create parasitic leakage paths at the interfaces of STI/Si, which increase the leakage current and reduce the positive shift of the threshold voltage. The parasitic effect generated by the positive charges of STI makes the threshold voltage of the narrow-channel device degrade more, and due to the gate edge effect, the threshold voltage of short-channel devices degrades more.

127I and 129I species in the English Channel and its adjacent areas: Uncovering impact on the isotopes marine pathways.

Radioactive iodine-129 has been released from the La Hague nuclear fuel reprocessing facility (NRF) into the English Channel, but the distribution and transformation of the isotope species, and environmental consequences have not been fully characterized in the Channel. Here we present data on iodine isotopes (129I and 127I) species in surface water of the English Channel and the southern Celtic Sea. Compared to 127I species, the concentrations of 129I- and 129IO3- show more variations, but iodate is the major species for both 129I and 127I. Our data provide new information regarding iodide-iodate inter-conversion showing that water dilution and mixing are the main factors affecting the 127I and 129I species distribution in the Channel. Some reduction of iodate occurs within the English Channel and mainly in the west part because of biotic processes. The 129I species transformation is overall insignificant, especially in the eastern Channel, where a constant value of 129IO3-/129I is observed, which might characterize the La Hague wastewater signal. In the Celtic Sea, oxidation of iodide can be traced by 127I and 129I species. On a larger scale, 129I generally experienced an oxidation process in the Atlantic Ocean, while in the coast of shallow shelf seas, new produced 129I- can be identified, especially in the German Bight and the Baltic Sea. The data of 129I species in the English Channel can provide estimate of redox rates in a much broader marine areas if the transit time of 129I from La Hague is well-defined. Furthermore, estimate of inventories for 129I and its species in the Channel, and fluxes of 129I species from the English Channel to the North Sea add important information to the geochemical cycle of 129I.

Systematic analysis of expression profiles of HMGB family members for prognostic application in non-small cell lung cancer.

Background: Lung cancer is a significant challenge to human health. Members of the high mobility group (HMG) superfamily (HMGB proteins) are implicated in a wide variety of physiological and pathophysiological processes, but the expression and prognostic value of HMGB family members in non-small cell lung cancer (NSCLC) have not been elucidated. Methods: In this study, ONCOMINE, UALCAN, GEPIA, Kaplan-Meier Plotter, starBase, OncomiR databases, and GeneMANIA were utilized to evaluate the prognostic significance of HMGB family members in NSCLC. Results: HMGB2/3 expression levels were higher in NSCLC patients. HMGB1 expression was higher in lung squamous cell carcinoma (LUSC) and was lower in lung adenocarcinoma (LUAD) tissue than in normal lung tissue. HMGB2 expression was related to cancer stage. Increased HMGB1 mRNA expression levels were associated with improved lung cancer prognosis, including overall survival (OS), first-progression survival (FP), and post-progression survival (PPS). There was no significant association between HMGB2 levels and prognostic indicators. HMGB3 expression was associated with poorer OS. GeneMANIA and GO/KEGG pathway analysis showed that HMGB family members mainly associated with chromosome condensation, regulation of chromatin organization, and nucleosome binding in NSCLC. HMGBs expression were closely correlated with infiltrating levels of specific types of immune cells in NSCLC, especially Th2 cells, Th17 cells, and mast cells. hsa-miR-25-3p, hsa-miR-374a-3p, and hsa-miR-93-5p were significantly positively correlated with HMGB1, HMGB2, and HMGB3, respectively. However, hsa-miR-30a-5p was predicted to significantly negatively regulate HMGB3 expression. Conclusion: Our study revealed that HMGB1 is positively related to the improved prognosis in NSCLC, and demonstrate that HMGB3 might be a risk factor for poorer survival of NSCLC patients.

Strategies for Targeting Neural Circuits: How to Manipulate Neurons Using Virus Vehicles.

Viral strategies are the leading methods for mapping neural circuits. Viral vehicles combined with genetic tools provide the possibility to visualize entire functional neural networks and monitor and manipulate neural circuit functions by high-resolution cell type- and projection-specific targeting. Optogenetics and chemogenetics drive brain research forward by exploring causal relationships among different brain regions. Viral strategies offer a fresh perspective for the analysis of the structure-function relationship of the neural circuitry. In this review, we summarize current and emerging viral strategies for targeting neural circuits and focus on adeno-associated virus (AAV) vectors.

The pathological involvement of spinal cord EphB2 in visceral sensitization in male rats.

Patients with post-traumatic stress disorder (PTSD) are usually at an increased risk for chronic disorders, such as irritable bowel syndrome (IBS), characterized by hyperalgesia and allodynia, but its subsequent effect on visceral hyperalgesia and the mechanism remain unclear. The present study employed single prolonged stress (SPS), a model of PTSD-pain comorbidity, behavioral evaluation, intrathecal drug delivery, immunohistochemistry, Western blotting, and RT-PCR techniques. When detecting visceral sensitivity, the score of the abdominal withdrawal reflex (AWR) induced by graded colorectal distention (CRD) was used. The AWR score was reduced in the SPS day 1 group but increased in the SPS day 7 and SPS day 14 groups at 40 mmHg and 60 mmHg, and the score was increased significantly with EphrinB1-Fc administration. The EphB2+ cell density and EphB2 protein and mRNA levels were downregulated in the SPS day 1 group and then upregulated significantly in the SPS day 7 group; these changes were more noticeable with EphrinB1-Fc administration compared with the SPS-only group. The C-Fos-positive reaction induced by SPS was mainly localized in neurons of the spinal dorsal horn, in which the C-Fos-positive cell density and its protein and mRNA levels were upregulated on SPS days 7 and 14; these changes were statistically significant in the SPS + EphrinB1-Fc group compared with the SPS alone group. The present study confirmed the time window for the AWR value, EphB2 and C-Fos changes, and the effect of EphrinB1-Fc on these changes, which suggests that spinal cord EphB2 activation exacerbates visceral pain after SPS.

eIF6 promotes the malignant progression of human hepatocellular carcinoma via the mTOR signaling pathway.

BACKGROUND: Eukaryotic translation initiation factor 6 (eIF6) has a crucial function in the maturation of 60S ribosomal subunits, and it controls the initiation of protein translation. Although emerging studies indicate that eIF6 is aberrantly expressed in various types of cancers, the functions and underlying molecular mechanisms of eIF6 in the pathological progression of hepatocellular carcinoma (HCC) remain unclear. This study aimed to evaluate the potential diagnostic and prognostic value of eIF6 in patients with HCC. METHODS: HCC samples enrolled from The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO) and our cohort were used to explore the role and mechanism of eIF6 in HCC. The diagnostic power of eIF6 was verified by receiver operating characteristic curve (ROC) analysis and its prognostic value was assessed by Kaplan-Meier analysis, and then related biological functions of eIF6 were determined in vitro and in vivo cancer models. In addition, potential molecular mechanism of eIF6 in HCC was unveiled by the gene set enrichment analysis and western blot assay. RESULTS: We demonstrated that eIF6 expression was markedly increased in HCC, and elevated eIF6 expression correlated with pathological progression of HCC. Besides, eIF6 served as not only a new diagnostic biomarker but also an independent risk factor for OS in HCC patients. Functional studies indicated that the deletion of eIF6 displayed tumor-suppressor activity in HCC cells. Furthermore, we found that eIF6 could activate the mTOR-related signaling pathway and regulate the expression level of its target genes, such as CCND1, CDK4, CDK6, MYC, CASP3 and CTNNBL1, and these activities promoted proliferation and invasion of HCC cells. CONCLUSIONS: The findings of this study provided a novel basis for understanding the potential role of eIF6 in promoting tumor growth and invasion, and exploited a promising strategy for improving diagnosis and prognosis of HCC.

Hypo-fractionation radiotherapy normalizes tumor vasculature in non-small cell lung cancer xenografts through the p-STAT3/HIF-1 alpha signaling pathway.

BACKGROUND: Hypo-fractionation radiotherapy (HFRT) was considered to be an important treatment for non-small cell lung cancer (NSCLC), but the radiobiological effects of HFRT on NSCLC remain unclear. The aim of this study was to investigate specific biological effect of HFRT on tumor angiogenesis, compared with conventional radiotherapy (CRT). METHODS: The subcutaneous xenograft models and the dorsal skinfold window chamber (DSWC) models of nude mice bearing H460 and HCC827 NSCLC cells were irradiated with doses of 0 Gy (sham group), 22 Gy delivered into 11 fractions (CRT group) or 12 Gy delivered into 1 fraction (HFRT group). At certain time-points after irradiation, the volumes, hypoxic area, coverage rate of pericyte and micro-vessel density (MVD) of the subcutaneous xenograft models were detected, and the tumor vasculature was visualized in the DSMC model. The expressions of phosphorylated signal transducer and activator of transcription (p-STAT3), hypoxia-inducible factor 1-α (HIF-1α), CXCL12 and VEGFA were detected. RESULTS: Compared with the CRT groups, HFRT showed more-efficient tumor growth-suppression, accompanied by a HFRT-induced window-period, during which vasculature was normalized, tumor hypoxia was improved and MVD was decreased. Moreover, during the window-period, the signal levels of p-STAT3/HIF-1α pathway and the expressions of its downstream angiogenic factors (VEGFA and CXCL12) were inhibited by HFRT. CONCLUSION: Compared with CRT, HFRT induced tumor vasculature normalization by rendering the remaining vessels less tortuous and increasing pericyte coverage of tumor blood vessels, thereby ameliorating tumor hypoxia and enhancing the tumor-killing effect. Moreover, HFRT might exert the aforementioned effects through p-STAT3/HIF-1α signaling pathway.

Accuracy of endoscopic ultrasound in rectal cancer and its use in transanal endoscopic microsurgery.

Introduction: This study evaluated the accuracy of endoscopic ultrasound (EUS) for preoperative staging of rectal cancer and guiding the treatment of transanal endoscopic microsurgery (TEM) in early rectal cancer.Material and methods: One-hundred-twenty-six patients with rectal cancer were staged preoperatively using EUS and the results were compared with postoperative histopathology results. Radical surgeries, including low anterior resection (LAR), abdominal-perineal resection (APR) and Hartmann surgeries, were performed on patients with advanced rectal cancers, and TEM was performed on patients with stage T1. The Kappa statistic was used to determine agreement between EUS-based staging and pathology staging.Results: The overall accuracies of EUS for T and N stage were 90.8% (Kappa = 0.709) and 76.7% (Kappa = 0.419), respectively. The accuracies of EUS for uT1, uT2, uT3, and uT4 stages were 96.8%, 92.1%, 84.1%, and 88.9%, respectively, and for uN0, uN1, and uN2 stages, they were 71.9%, 64.9%, and 93.0%, respectively. Twelve patients underwent TEM and received confirmed pathology results of early rectal cancer. After postoperative follow-up, there were no local recurrences or distant metastases.Conclusion: EUS is a good and comparable technique for postoperative staging of rectal cancer. Moreover, EUS is used as indicator for preoperative staging and tumor assessment strategy when considering TEM.

Anatomical Study of the Descending Genicular Artery Chimeric Flaps.

Purpose: With increasing use of the chimeric flap of the descending genicular artery, the authors systematically investigated the anatomy of its branches in cadavers. Methods: Fifteen fresh cadaveric thighs were studied by anatomical dissection. The branches of the descending genicular arteries were skeletonized along their courses to the femoral arteries. Branches' lengths and diameters were measured to simulate the combined application of the skin, muscle, bone, osteochondral and osteocutaneous flaps with tendon enthesis. Results: The descending genicular artery was noted in 11 thighs, with an average diameter of 1.94 ± 0.36 mm and an average length of 10.69 ± 4.41 mm. In addition, the saphenous artery was noted in all 15 thighs, and the average diameter of the original part was 1.35 ± 0.18 mm. Branches arose from the saphenous artery to supply the skin above the knee, the anterior of tibia, the sartorius muscle and the pes anserinus. The average diameter of the osteoarticular artery was 1.80 ± 0.46 mm which divaricated into a periosteal branch to supply the bone above the medial femoral epicondyle and a few articular branches to supply the bone and the cartilage of the medial femoral condyle. Conclusions: This study systematically investigated the anatomy of the descending genicular artery and its branches. Based on the anatomical features of descending genicular artery, chimeric flap offers combination therapy with other tissue flaps. Besides, considering its long chimeric arm, chimeric flap could be used to repair not only local complex injuries but also defects in different locations. Clinical Relevance: The descending genicular artery chimeric flap is a clinical option for reconstructing compound tissue defects of limbs.

Use of Hisense Computer-Assisted Surgery System Enhances Infrapyloric Lymph Node Dissection for Gastric Cancer.

BACKGROUND: This study aimed to establish a three-dimensional model of infrapyloric vessels using the Hisense computer-assisted surgery (CAS) system before the operation to understand blood vessel variation types and determine the group 6 lymph node (LN) metastasis status. METHODS: One hundred and four gastric cancer patients were randomly assigned to a CAS group and a computed tomography (CT) group. Intraoperative and postoperative complications in the two groups were recorded. The number of group 6 LNs dissected and the metastasis status were compared between the groups. The independent risk factors influencing group 6 LN metastasis were determined by multiple logistic regression analysis. RESULTS: In the 50 CAS group patients, the gastrocolic trunk of Henle was divided into a gastrocolic type (34.0%) and a gastropancreatic colonic type (66.0%); the right gastroepiploic artery was divided into a coarse blood supply type (24.0%) and a fine blood supply type (76.0%); and the relationship between the right gastroepiploic artery and right gastroepiploic vein was divided into an adjacent type (58.0%) and a separated type (42.0%). Although the difference was not significant, the CAS group had fewer cases of intraoperative gastrocolic trunk injury and postoperative pancreatic leakage in trend than the CT group. The CAS group had more dissected LNs (P < 0.001) and metastatic LNs (P = 0.011) than the CT group; meanwhile, it had higher LN metastasis rate and LN metastasis degree in trend than the CT group. According to the multiple logistic regression model, tumor location and TNM stage were significantly correlated with group 6 LN metastases. CONCLUSIONS: By establishing a three-dimensional model of the infrapyloric vessels using the Hisense CAS system, we comprehensively determined the anatomic variations in each collateral vessel. The application of the Hisense CAS system significantly improved the number of LNs dissected and the discovery rate of LN metastases without increasing the incidence of complications.

Dynamic expression of matrix metalloproteinases 2, 9 and 13 in ovariectomy-induced osteoporosis rats.

The aim of the present study was to examine the dynamic expression of matrix metalloproteinase (MMP)-2, MMP-9 and MMP-13 in an ovariectomy (OVX)-induced osteoporosis rat model. A total of 80 Sprague-Dawley female rats (age, 3 months) were randomly divided into the OVX and sham groups, with 40 rats in each group. Rats in the sham group received sham surgery, while the remaining rats were ovariectomized. After 12, 16, 20 and 24 weeks, 10 rats from each group were randomly sacrificed, respectively. It was observed that the bone mineral density (BMD) and the trabecular bone area in the OVX group were significantly lower as compared with those in the sham group (P<0.01). The expression levels of MMP-2 and MMP-9 were negatively correlated with the BMD, while MMP-13 was positively correlated with the BMD. The expression levels of MMP-2 and MMP-9 increased more abruptly and were significant higher in the OVX group in comparison with those in the sham group between 12 and 24 weeks after surgery (P<0.01). More specifically, the MMP-9 mRNA expression level in the OVX group increased abruptly between 12 and 24 weeks after surgery. By contrast, in the sham group, the MMP-9 mRNA level was undetectable between 12 and 16 weeks, and increased steadily between 16 and 24 weeks. Furthermore, the mRNA and protein expression levels of MMP-13 initially increased and then decreased in the OVX group (P<0.01 vs. the sham group), whereas they continuously increased in the sham group between 12 and 24 weeks after surgery. In conclusion, MMP-2, MMP-9 and MMP-13 regulated the development of osteoporosis, and MMP-9 may be used as an important marker in the early diagnosis of osteoporosis.

Identification of Metastatic Lymph Nodes in MR Imaging with Faster Region-Based Convolutional Neural Networks.

MRI is the gold standard for confirming a pelvic lymph node metastasis diagnosis. Traditionally, medical radiologists have analyzed MRI image features of regional lymph nodes to make diagnostic decisions based on their subjective experience; this diagnosis lacks objectivity and accuracy. This study trained a faster region-based convolutional neural network (Faster R-CNN) with 28,080 MRI images of lymph node metastasis, allowing the Faster R-CNN to read those images and to make diagnoses. For clinical verification, 414 cases of rectal cancer at various medical centers were collected, and Faster R-CNN-based diagnoses were compared with radiologist diagnoses using receiver operating characteristic curves (ROC). The area under the Faster R-CNN ROC was 0.912, indicating a more effective and objective diagnosis. The Faster R-CNN diagnosis time was 20 s/case, which was much shorter than the average time (600 s/case) of the radiologist diagnoses.Significance: Faster R-CNN enables accurate and efficient diagnosis of lymph node metastases. Cancer Res; 78(17); 5135-43. ©2018 AACR.

Long-term electroacupuncture stimulation prevents osteoporosis in ovariectomised osteopaenic rats through multiple signalling pathways.

BACKGROUND: The pathogenic mechanisms of postmenopausal osteoporosis (PMOP) development are complex and are related to multiple cellular signalling transduction pathways. The aim of this study was to compare the effects of electroacupuncture (EA) at GV4/GV6 versus BL20/BL23 on the bones in ovariectomised (OVX) rats to explore the pathways that mediate the effects of EA on bone. METHODS: Forty female Sprague-Dawley rats were allocated to one of four groups (n=10 rats each) that received sham surgery (Sham group), OVX surgery only (OVX group), OVX surgery plus EA at GV4/GV6 (GV group) and OVX surgery plus EA at BL20/BL23 (BL group). Bone turnover markers osteocalcin (OC) and tartrate-resistant acid phosphatase 5b (TRACP 5b) were measured in serum, and bone mineral density (BMD) of the lumbar vertebrae and histomorphology of the femur were evaluated. Moreover, the expression of osteoprotegerin (OPG) and receptor activator of nuclear factor-κB ligand (RANKL) was detected by ELISA. The expression of lipoprotein receptor-related protein (LRP) 5, ß-catenin, runt-related transcription factor (Runx) 2 involving Wnt/ß-catenin signalling and p38, c-Jun N-terminal kinase (JNK) and extracellular regulated protein kinases 1/2 involving mitogen-activated protein kinase signalling were determined by Western blotting. RESULTS: The two EA-treated groups demonstrated increased levels of OC and the BMD of lumbar vertebrae, decreased levels of TRACP 5b and improved bone microstructure in the femur, compared with the untreated OVX group (P<0.05). Histomorphology analysis showed that EA treatment significantly increased the values of the trabeculae (µm), trabecular area (%) and trabecular bone number (per mm) and reduced trabecular separation (mm), compared with the OVX group. In addition, the ratio of OPG to RANKL and LRP5, ß-catenin and Runx2 expression were significantly upregulated, while the expression of phosphorylated (p)-p38 and p-JNK were downregulated in EA-treated groups compared with the OVX group. CONCLUSION: EA attenuates PMOP and it appears that the mechanism involves the regulation of multiple targets and pathways.

A New Chinese Medicine Intestine Formula Greatly Improves the Effect of Aminosalicylate on Ulcerative Colitis.

Ulcerative colitis (UC) is a chronic lifelong inflammatory disorder of the colon. Current medical treatment of UC relies predominantly on the use of traditional drugs, including aminosalicylates, corticosteroids, and immunosuppressants, which failed to effectively control this disease's progression and produced various side effects. Here, we report a new Chinese medicine intestine formula (CIF) which greatly improved the effect of mesalazine, an aminosalicylate, on UC. In the present study, 60 patients with chronic UC were treated with oral mesalazine alone or in combination with CIF enema. The combination of mesalazine and CIF greatly and significantly improved the clinical symptoms and colon mucosal condition and improved the Mayo Clinic Disease Activity Index and health-related quality of life, when compared to mesalazine alone. In particular, the addition of CIF further decreased serum levels of tumor necrosis factor-alpha and hypersensitivity C-reactive protein but in contrast increased interleukin-4. Thus, the results demonstrate the beneficial role of CIF in UC treatment, which may be mediated by the regulation of inflammation.

Electroacupuncture at the governor vessel and bladder meridian acupoints improves postmenopausal osteoporosis through osteoprotegerin/RANKL/RANK and Wnt/ß-catenin signaling pathways.

Previous studies have demonstrated that pretreatment with electroacupuncture (EA) at the zusanli/ST36 and sanyinjiao/SP6 acupoints prevents ovariectomy-induced osteoporosis in rats; however, the therapeutic effects of EA at the governor vessel (GV) and bladder meridian (BL) acupoints remain unclear. In the present study, the effects of EA at the GV4, GV6, BL20 and BL23 acupoints on the bones of ovariectomized (OVX) rats were investigated to identify the pathways that mediate the action of EA on the bones. A postmenopausal osteoporosis model was established by performing an ovariectomy in six-month-old female Sprague Dawley rats. Following the ovariectomy, EA treatment was administered once per day for 90 days, with an interval of 5 days per 10 days. The changes in the serum levels of estradiol (E2) and the bone turnover markers, osteocalcin (OC) and tartrate-resistant acid phosphatase 5b (TRACP 5b), were determined, while the bone mineral density (BMD) of the lumbar vertebra and the histomorphology of the femur were observed. Furthermore, the expression of osteoprotegerin (OPG) and receptor activator of nuclear factor-κB ligand (RANKL), which are involved in the OPG/RANKL pathway, were detected by ELISA. In addition, the protein expression levels of low-density lipoprotein receptor-related protein (LRP) 5, ß-catenin and runt-related transcription factor (Runx) 2, which are involved in the Wnt/ß-catenin signaling pathway, were detected by western blot analysis. The results revealed that the GV and BL EA treatment groups significantly increased the serum levels of E2 and OC, decreased the serum levels of TRACP 5b and increased the BMD of the lumbar vertebra when compared with the OVX group. With regard to the histomorphology of the bone tissue, an ordered arrangement and a slight thinning of the trabeculae, with no evident hairline fractures, was observed in the femurs following EA treatment in the OVX rats. Furthermore, histomorphological analysis revealed that EA treatment significantly increased the values of the bone histomorphometry indices, trabecular area percentage, trabecular thickness and trabecular number, and reduced the value of trabecular separation, as compared with the OVX group. In addition, the ratio of OPG/RANKL expression was significantly upregulated, and the expression levels of LRP5, ß-catenin and Runx2 were significantly upregulated in the EA treatment groups. Therefore, these results demonstrated that long-term stimulation with EA treatment at the GV and BL acupoints was able to alleviate osteoporosis induced by an ovariectomy through regulating the OPG/RANKL and Wnt/ß-catenin signaling pathways.

Efficient gene carriers composed of 2-hydroxypropyl-ß-cyclodextrin, ethanolamine-functionalized poly(glycidyl methacrylate), and poly((2-dimethyl amino)ethyl methacrylate) by combination of ATRP and click chemistry.

In this work, a simple one-step method is first employed to produce the bromoisobutyryl-terminated 2-hydroxypropyl-ß-cyclodextrin (HPCD-Br). The pendant epoxy groups of poly(glycidyl methacrylate) block prepared via ATRP from HPCD-Br can be reacted with ethanolamine to produce HPCD-PGEA which exhibits much lower cytotoxicity and better gene transfection yield than polyethylenimine (25 kDa) in COS7 and HepG2 cell lines. Moreover, poly((2-dimethyl amino)ethyl methacrylate) blocks can be incorporated into low-molecular-weight HPCD-PGEA via "click" reaction to further enhance the gene transfection efficiency in HepG2 cell lines.