Tetraspanin Tspan8 restrains interferon signaling to stabilize intestinal epithelium by directing endocytosis of interferon receptor.

Inflammation can impair intestinal barrier, while increased epithelial permeability can lead to inflammation. In this study, we found that the expression of Tspan8, a tetraspanin expressed specifically in epithelial cells, is downregulated in mouse model of ulcerative disease (UC) but correlated with those of cell-cell junction components, such as claudins and E-cadherin, suggesting that Tspan8 supports intestinal epithelial barrier. Tspan8 removal increases intestinal epithelial permeability and upregulates IFN-γ-Stat1 signaling. We also demonstrated that Tspan8 coalesces with lipid rafts and facilitates IFNγ-R1 localization at or near lipid rafts. As IFN-γ induces its receptor undergoing clathrin- or lipid raft-dependent endocytosis and IFN-γR endocytosis plays an important role in Jak-Stat1 signaling, our analysis on IFN-γR endocytosis revealed that Tspan8 silencing impairs lipid raft-mediated but promotes clathrin-mediated endocytosis of IFN-γR1, leading to increased Stat1 signaling. These changes in IFN-γR1 endocytosis upon Tspan8 silencing correlates with fewer lipid raft component GM1 at the cell surface and more clathrin heavy chain in the cells. Our findings indicate that Tspan8 determines the IFN-γR1 endocytosis route, to restrain Stat1 signaling, stabilize intestine epithelium, and subsequently prevent intestine from inflammation. Our finding also implies that Tspan8 is needed for proper endocytosis through lipid rafts.

Buffalo yogurt fermented with commercial starter and Lactobacillus plantarum originating from breast milk lowered blood pressure in pregnant hypertensive rats.

Nutritional therapy, which may have advantages over medication, is being investigated as a novel treatment for pregnancy-induced hypertension. Several studies have shown that probiotic yogurt supplementation during pregnancy has beneficial effects on maternal and fetal health. In this study, fermented buffalo milk was produced with yogurt culture and Lactobacillus plantarum B, a probiotic isolated from healthy breast milk with high angiotensin-converting enzyme inhibitory activity. The fermentation conditions under which the angiotensin-converting enzyme (ACE) inhibitory activity reached 84.51% were optimized by the response surface method as follows: 2 × 106 cfu/mL of L. plantarum B, yogurt culture 2.5 × 105 cfu/mL, and 8 h at 37°C. The distribution of ACE inhibitory peptides from fermented buffalo milk and fermented cow milk were further analyzed by liquid chromatography-mass spectrometry. By searching according to the structural features of ACE inhibitory peptides, 29 and 11 peptides containing ACE inhibitory peptide features were found in fermented buffalo milk and fermented cow milk, respectively. To investigate the in vivo antihypertensive activity of fermented buffalo milk, 18 pregnant rats were divided into 3 groups (n = 6 in each group) and administered 10 mL of normal saline, yogurt (20 mg/kg), or labetalol hydrochloride (4 mg/kg) daily from the beginning of pregnancy to parturition. To induce hypertension, methyl nitrosoarginine (125 mg/kg) was injected subcutaneously every day from d 15 of pregnancy to the day of delivery. Blood pressure was not significantly changed in the yogurt and labetalol groups after induction of hypertension and was lower compared with the normal saline group, but there was no difference between the yogurt and labetalol groups. This implied that the buffalo yogurt had a preventive and antihypertensive effect in the pregnancy-induced hypertensive rat model. Further studies to determine the mechanism of action, as well as a randomized control trial, are warranted.

Early-onset pharyngeal airway collapse in infants: a retrospective single-center study.

BACKGROUND: Early-onset pharyngeal airway collapse (PAC) in infants, which presents with onset within 6-months old is relatively rare. This disease has not been given enough attention in clinic. The aim of this study was to explore the clinical features, endoscopic findings and outcomes of early-onset PAC in infants. METHODS: The children of PAC with onset within 6-months old were included. A retrospective study was conducted. RESULTS: (1) Total 26 cases were included. The age of onset was neonatal period in 20 cases, 1 to 3-months old in 5 cases, and 4 to 6-months old in 1 case. (2) The main clinical manifestations were noisy breathing (26/26), suprasternal retraction (18/26), snoring (14/26) and hypoxic episode (13/26). (3) Based on the endoscopic findings, collapse at the retropalatal level was most common (24/26). (4) Twelve cases underwent pharyngolaryngeal CT examination, which revealed abnormal findings in 7 cases. (5) Fifteen cases were accompanied with the other airway malformations. (6) In the group with comorbidities of cerebral impairment or craniofacial abnormalities, 1 case was lost to follow up, 4 cases died, and 10 cases survived, in which 9 cases had neurodevelopmental disorders. In the group without comorbidities, 2 cases were lost to follow up, 9 cases survived, in which 1 case had neurodevelopmental disorders. The incidence of poor prognosis including death and neurodevelopmental disorders was significantly higher in the group with comorbidities than that without comorbidities (P<0.01). (7) An symptomatic improvement of PAC was found in the majority of the survived cases (18/19) with age. CONCLUSIONS: Early-onset PAC in infants usually exhibits varying degrees of relief with age, whereas the cases with comorbidities had a poor prognosis.

[CT-Based Weighted Radiomic Score Predicts Tumor Response to Immunotherapy in Non-Small Cell Lung Cancer].

Objective To develop a CT-based weighted radiomic model that predicts tumor response to programmed death-1(PD-1)/PD-ligand 1(PD-L1)immunotherapy in patients with non-small cell lung cancer.Methods The patients with non-small cell lung cancer treated by PD-1/PD-L1 immune checkpoint inhibitors in the Peking Union Medical College Hospital from June 2015 to February 2022 were retrospectively studied and classified as responders(partial or complete response)and non-responders(stable or progressive disease).Original radiomic features were extracted from multiple intrapulmonary lesions in the contrast-enhanced CT scans of the arterial phase,and then weighted and summed by an attention-based multiple instances learning algorithm.Logistic regression was employed to build a weighted radiomic scoring model and the radiomic score was then calculated.The area under the receiver operating characteristic curve(AUC)was used to compare the weighted radiomic scoring model,PD-L1 model,clinical model,weighted radiomic scoring + PD-L1 model,and comprehensive prediction model.Results A total of 237 patients were included in the study and randomized into a training set(n=165)and a test set(n=72),with the mean ages of(64±9)and(62±8)years,respectively.The AUC of the weighted radiomic scoring model reached 0.85 and 0.80 in the training set and test set,respectively,which was higher than that of the PD-L1-1 model(Z=37.30,P<0.001 and Z=5.69,P=0.017),PD-L1-50 model(Z=38.36,P<0.001 and Z=17.99,P<0.001),and clinical model(Z=11.40,P<0.001 and Z=5.76,P=0.016).The AUC of the weighted scoring model was not different from that of the weighted radiomic scoring + PD-L1 model and the comprehensive prediction model(both P>0.05).Conclusion The weighted radiomic scores based on pre-treatment enhanced CT images can predict tumor responses to immunotherapy in patients with non-small cell lung cancer.

A Review of Circulating Tumor DNA in the Diagnosis and Monitoring of Esophageal Cancer.

Circulating tumor DNA (ctDNA) is a type of cell-free DNA released by tumor cells after necrosis and apoptosis, and it can be actively secreted by tumor cells. Since ctDNA is derived from various tumor sites, it can provide far more comprehensive genomic and epigenomic information than a single-site biopsy. Therefore, ctDNA can overcome tumor heterogeneity, which is the major limitation of a traditional tissue biopsy approach. Noninvasive ctDNA assays allow continuous real-time monitoring of the molecular status of cancers. Recently, ctDNA assays have been widely used in clinical practice, including cancer diagnosis, evaluation of therapeutic efficacy and prognosis, and monitoring of relapse and metastasis. Although ctDNA shows a high diagnostic performance in advanced esophageal cancer, it is far from satisfactory for early diagnosis of esophageal cancer. Monitoring the dynamic changes of ctDNA is beneficial for the evaluation of therapeutic efficacy and prediction of early recurrence in esophageal cancer. It is necessary to establish standards for individualized ctDNA detection in the evaluation of treatment response and surveillance of esophageal cancer and to develop clinical practice guideline for the systemic treatment of patients with "ctDNA recurrence." This review aims to provide an update on the role of ctDNA in the diagnosis and monitoring of esophageal cancer.

Recent advances in near-infrared II imaging technology for biological detection.

Molecular imaging technology enables us to observe the physiological or pathological processes in living tissue at the molecular level to accurately diagnose diseases at an early stage. Optical imaging can be employed to achieve the dynamic monitoring of tissue and pathological processes and has promising applications in biomedicine. The traditional first near-infrared (NIR-I) window (NIR-I, range from 700 to 900 nm) imaging technique has been available for more than two decades and has been extensively utilized in clinical diagnosis, treatment and scientific research. Compared with NIR-I, the second NIR window optical imaging (NIR-II, range from 1000 to 1700 nm) technology has low autofluorescence, a high signal-to-noise ratio, a high tissue penetration depth and a large Stokes shift. Recently, this technology has attracted significant attention and has also become a heavily researched topic in biomedicine. In this study, the optical characteristics of different fluorescence nanoprobes and the latest reports regarding the application of NIR-II nanoprobes in different biological tissues will be described. Furthermore, the existing problems and future application perspectives of NIR-II optical imaging probes will also be discussed.

[Stakeholder Analysis of the Application of Artificial Intelligence in the Field of Primary Health Care].

The application of artificial intelligence in the field of primary health care can effectively improve diagnosis and treatment,avoid over-examination and over-medication,and make up for the shortage of high-quality medical resources in primary medical and health institutions.Focusing on the application of artificial intelligence in the field of primary health care,this paper analyzes the existing application modes and typical cases,studies its main stakeholders,interest demands and problems,and provides corresponding suggestions.

Number of Stent Retriever Passes Associated with Clinical Outcome After Mechanical Thrombectomy in Acute Ischemic Stroke.

OBJECTIVE: To evaluate the association between the number of stent retriever (SR) passes and clinical outcome after mechanical thrombectomy (MT) in patients with acute ischemic stroke(AIS). METHODS: We retrospectively analyze data collected from consecutive patients with large vessel occlusion (LVO) in anterior circulation treated with MT. Baseline characteristics, number of SR passes, symptomatic intracranial hemorrhage (sICH), clinical outcome measured by modified Rankin Scale (mRS) at 90 days after MT were collected. Multivariate logistic regression analysis was performed to assess the association between number of SR passes and patients' clinical outcome. RESULTS: 134 patients with LVO achieved successful reperfusion (mTICI 2B/3) were enrolled. Univariate analysis showed that patients with favorable outcomes were less likely to need more than three passes of SR (9.8%vs39.7%, p = 0.001). In a multivariable analysis, baseline NIHSS score (OR 0.922, 95%CI 0.859∼0.990, p = 0.025), more than three passes of SR (OR 0.284, 95%CI0.091∼0.882, p = 0.030) and symptomatic intracranial hemorrhage (OR 0.116,95%CI0.021∼0.650, p = 0.014) each independently predicted poor outcome after MT at 90 days. CONCLUSION: The need for more than three passes of SR may be used as an independent predictor of poor outcome after MT in patients with acute ischemic stroke at 90 days.

[Component analysis of Ophiocordyceps lanpingensis polysaccharides and study on alleviation of hepatic fibrosis in mice by polysaccharides].

Ophiocordyceps lanpingensis is mainly used as an ethnic medicine to treat the diseases of liver, kidney and other diseases, but the pharmacological mechanism is not clear yet. In this study, the components and contents of monosaccharides in the O.lanpingensis polysaccharides(OLP) were analyzed. The results showed that the OLP were composed of mannose, glucose, galactose and arabinose, with mass percentages of 19.1%, 21.8%, 21.1%, and 38.0%, respectively. Based on the hepatic fibrosis model induced by CCl_4 in mice, OLP could significantly relieve the inflammation and fibrosis levels of hepatic tissues, reverse the CCl_4-induced increasing levels of alanine aminotransferase(ALT) and aspartate aminotransferase(AST) in mice serum, and recover the functions of liver to a normal state. This study proved that OLP significantly decreased the mRNA expression levels of fibrotic genes, alpha-smooth muscle actin(α-SMA) and collagen type 1(Col-1), as well as the content of hydroxyproline(HYP) in the liver tissues; meanwhile, the contents of antioxidants superoxide dismutase(SOD) and glutathione(GSH) were enhanced and the production of lipid peroxide malondialdehyde(MDA) was reduced. Moreover, OLP inhibited the gene expression levels of tumor necrosis factor-α(TNF-α), interleukin-6(IL-6) and nuclear factor kappa B(NF-κB) in the livers of mice. Further study indicated that OLP could restrain the apoptosis of hepatic cells due to the decrease of the apoptosis index and down-regulations of protein expression levels of Bcl-2 associated X protein(Bax), cysteinyl aspartate specific proteinase-3(caspase-3) and cysteinyl aspartate specific proteinase-9(caspase-9), and the promotion of protein expression level of B-cell lymphoma-2(Bcl-2) in livers. To sum up, the mechanism of OLP for alleviating hepatic fibrosis was likely related to the synergy by remitting the oxidative stress of the body, alleviating inflammatory response, anti-apoptosis of hepatic cells, and so on.

MicroRNA-27a-3p inhibits cell viability and migration through down-regulating DUSP16 in hepatocellular carcinoma.

MicroRNA (miRNA or miR) has been shown to play an important role in the initiation and development in many different cancers. Here, we demonstrated down-regulated expression of miR-27a-3p in hepatocellular carcinoma (HCC) tissues in comparison with that in adjacent normal liver tissues based on the TCGA database. Cells viability and apoptosis was measured by CCK-8 and flow cytometry assay. Cell invasion and migration was measured by Transwell and wound healing assay. The effect of miR-27a-3p on DUSP16 expression was evaluated by luciferase assays, and western blot assay. miR-27a-3p up-regulation by transfection with miR-27a-3p mimics attenuated SMMC-7721 and HepG2 cell viability, invasion as well as migration, obviously. Moreover, we found that dual specificity phosphatase 16 (DUSP16), also known as mitogen-activated protein kinase phosphatase 7 (MKP-7), is a target of miR-27a-3p. DUSP16 expression was obvious decrease by miR-27a-3p at both transcriptional and protein levels in both SMMC-7721 and HepG2 cells. DUSP16 expression in tissues of HCC was up-regulated in comparison with that in tissues of adjacent liver based on the TCGA database. Overexpression of DUSP16 significantly reversed the cell changes in viability, invasion and migration which resulted from miR-27a-3p up-regulation in SMMC-7721 and HepG2 cells. Our findings contribute to current understanding of the functions of miR-27a-3p and suggest a mechanism by which miR-27a-3p plays an anti-tumor role in the development of HCC by targeting DUSP16.

Visual targeted therapy of hepatic cancer using homing peptide modified calcium phosphate nanoparticles loading doxorubicin guided by T1 weighted MRI.

Effective treatment and real-time monitoring of hepatic cancer are essential. A multifunctional calcium phosphate nanoparticles loading chemotherapeutic agent doxorubicin and magnetic resonance imaging contrast agent diethylenetriaminepentaacetic acid gadolinium (A54-CaP/Gd-DTPA/DOX) was developed for visual targeted therapy of hepatic cancer via T1-weighted MRI in real-time. A54-CaP/Gd-DTPA/DOX exhibited a higher longitudinal relaxivity (6.02 mM-1 s-1) than commercial MR contrast agent Gd-DTPA (3.3765 mM-1 s-1). The DOX release from the nanoparticles exhibited a pH dependent behavior. The cellular uptake results showed that the internalization of A54-CaP/Gd-DTPA/DOX into BEL-7402 cells was1.9-fold faster than that of HepG2 cells via A54 binding. In vivo experiments presented that A54-CaP/Gd-DTPA/DOX had higher distribution and longer retention time in tumor tissue than CaP/Gd-DTPA/DOX and free DOX, and also displayed great antitumor efficacy (95.38% tumor inhibition rate) and lower toxicity. Furthermore, the Gd-DTPA entrapped in the nanoparticles could provide T1-weighted MRI for real-time monitoring the progress of tumor treatment.

ShRNA knock-down of CXCR7 inhibits tumour invasion and metastasis in hepatocellular carcinoma after transcatheter arterial chemoembolization.

To investigate the effects of lentiviral vector-mediated shRNA suppressing CXCR7 on tumour invasion and metastasis in hepatocellular carcinoma (HCC) after transcatheter arterial chemoembolization (TACE). HCCLM3 cell lines were cultured and assigned into the CXCR7-shRNA, negative control (NC) and blank groups. The qRT-PCR and Western blotting were applied to detect the mRNA and protein expressions of CXCR7, CXCR4 and MMP-2 in HCCLM3 cells. Cell proliferation and invasion were evaluated by MTT and Transwell assays. A Buffalo rat model of HCC was established. Fifty model rats were divided into the CXCR7-shRNA + TACE, CXCR7-shRNA, TACE, NC and control groups. Immunohistochemistry was performed to detect the expressions of CXCR7, MMP-2, vascular endothelial growth factor (VEGF) and intratumoral CD31-positive vessel count in tumour tissues of mice. Compared with the blank and NC groups, the mRNA and protein expressions of CXCR7 and MMP-2 were decreased in the CXCR7-shRNA group. The cell proliferation and invasion rates of the CXCR7-shRNA group were lower than the blank and NC groups. At the 4th week after TACE, tumour weight of the CXCR7-shRNA + TACE group increased continuously. The CXCR7-shRNA + TACE group showed longer survival time and smaller tumour sizes than other groups. Compared with other groups, the CXCR7-shRNA + TACE and CXCR7-shRNA groups had less number of lung metastatic nodules and lower expressions of CXCR7, MMP-2, VEGF and CD31-positive vessel count. CXCR7-shRNA inhibits tumour invasion and metastasis to improve the efficacy of TACE in HCC by reducing the expressions of CXCR7, MMP-2 and VEGF.

Evaluation of the blood supply and efficacy of transcatheter arterial chemoembolization for patients with liver metastasis using 18F-fluorodeoxyglucose positron emission tomography/computed tomography.

Our study aims to evaluate the efficacy of transcatheter arterial chemoembolization in the treatment of patients with liver metastasis using integrated 18F-fluorodeoxyglucose positron emission tomography/computed tomography. A total of 97 liver metastasis patients treated by transcatheter arterial chemoembolization were enrolled in this study. The 18F-fluorodeoxyglucose positron emission tomography/computed tomography images of liver metastasis patients were collected before and after transcatheter arterial chemoembolization treatment. The efficacy of transcatheter arterial chemoembolization for the treatment of liver metastasis was evaluated according to the revised Response Evaluation Criteria in Solid Tumors guidelines. The receiver operating characteristic curve analysis was used to determine cut-off values of 18F-fluorodeoxyglucose positron emission tomography parameters (Tsuvmax, Tsuvmax/Lsuvmax, and Tsuvmax/Lsuvmean) for predicting the efficacy of transcatheter arterial chemoembolization. Progression-free survival and the incidence of postoperative complications were compared. Correlation of Tsuvmax, Tsuvmax/Lsuvmax, and Tsuvmax/Lsuvmean with blood supply and lipiodol deposition in the lesion was analyzed. Among three 18F-fluorodeoxyglucose positron emission tomography parameters, the receiver operating characteristic analysis showed that Tsuvmax/Lsuvmax with a cut-off value of 3.56 was the best predictor of transcatheter arterial chemoembolization efficacy. According to the cut-off value of Tsuvmax/Lsuvmax, liver metastasis patients were divided into the Tsuvmax/Lsuvmax ≤ 3.56 and Tsuvmax/Lsuvmax > 3.56 groups. Compared with the Tsuvmax/Lsuvmax > 3.56 group, the Tsuvmax/Lsuvmax ≤ 3.56 group showed a longer progression-free survival and a lower incidence of postoperative complications. The Tsuvmax, Tsuvmax/Lsuvmax, and Tsuvmax/Lsuvmean in the lesion with abundant blood supply were significantly lower than those in peripheral liver parenchyma, while the Tsuvmax, Tsuvmax/Lsuvmax, and Tsuvmax/Lsuvmean in the lesion with lack of blood supply were significantly higher than those in peripheral liver parenchyma. Spearman correlation analysis indicated that lipiodol deposition in the lesion was positively correlated with the Tsuvmax, Tsuvmax/Lsuvmax, and Tsuvmax/Lsuvmean. The Tsuvmax/Lsuvmax of 18F-fluorodeoxyglucose positron emission tomography/computed tomography may be a good tool for predicting the blood supply and efficacy of transcatheter arterial chemoembolization for patients with liver metastasis.

The Value of the Score for the Targeting of Atrial Fibrillation (STAF) Screening in Acute Stroke Patients.

BACKGROUND AND PURPOSE: Recently, the score for the targeting of atrial fibrillation (STAF) was introduced to identify the risk of atrial fibrillation (AF) in stroke patients. In this study, we aim to evaluate the usefulness of the STAF score for AF screening in acute stroke patients. METHODS: Patients with acute ischemic stroke who were admitted to our stroke unit were prospectively enrolled from March 2011 to March 2013. Baseline National Institutes of Health Stroke Scale (NIHSS), left atrial dilatation, and vascular etiology were assessed to calculate the STAF score. Logistic regression analysis was used to examine the relationship between AF and STAF factors. Univariate analysis of AF and age, history of coronary heart disease and rheumatic heart disease, NIHSS, left atrial dilatation, and vascular etiology was performed. RESULTS: A total of 472 patients were enrolled in our analysis. AF was documented in 78 (16.53%) patients, of which 50% were paroxysmal. Multivariable analysis demonstrated that age, NIHSS, left atrial dilatation, and the absence of vascular etiology can each function as independent predictors for AF. In addition, all AF patients with a STAF ≥5 show a sensitivity of 76.92% and a specificity of 78.68%. The area under the receiver operating characteristic for all AF patients was .842 versus .763 for the paroxysmal AF (pAF) patients. In addition, a sensitivity of 81% (95% CI 73-92) and a ROC of .829 were for new-AF. CONCLUSIONS: The value of the STAF system for predicting the risk of pAF and new-AF in stroke patients is relatively limited.

MiR-363-3p inhibits the epithelial-to-mesenchymal transition and suppresses metastasis in colorectal cancer by targeting Sox4.

Epithelial-to-mesenchymal transition (EMT) plays an essential role in cancer invasion and metastasis and is associated with tumor recurrence in colorectal cancer (CRC). However, the mechanism that contributes to EMT have not been fully understood in CRC. In the present study, we showed that miR-363-3p was frequently down-regulated in CRC tissue specimens with lymph node metastasis. Moreover, we demonstrated that down-regulation of miR-363-3p promoted CRC cell migration and invasion, and induced EMT in vitro and in vivo, revealing that miR-363-3p playes a potential tumor-suppressive role in CRC. Analysis of the underlying mechanisms revealed that miR-363-3p could regulate Sox4 expression by directly targeting its 3'untranslated region. Down-regulation of miR-363-3p increased Sox4 expression and induced EMT, while overexpression of miR-363-3p decreased Sox4 expression. Taken together, our findings indicate that miR-363-3p is involved in CRC metastasis and functions as a tumor suppressor via negatively regulating Sox4. Therefore, the up-regulation of miR-363-3p in human CRC may have therapeutic benefits.

Low bone turnover and reduced angiogenesis in streptozotocin-induced osteoporotic mice.

It is known that type 1 diabetes (T1D) reduces bone mass and increases the risk for fragility fractures, an effect that has been largely ascribed to decreased bone formation. However, the potential role of decreased angiogenesis as a factor in osteogenesis reduction has not been extensively studied. Furthermore, there is controversy surrounding the effect of T1D on bone resorption. This study characterized bone microstructure, bone strength, and bone turnover of streptozotocin (STZ)-induced diabetic mice (T1D mice) and explored the role of angiogenesis in the pathogenesis of T1D-induced osteoporosis. Results demonstrate that T1D deteriorated trabecular microarchitecture and led to reduced bone strength. Furthermore, T1D mice showed reduced osteoblast number/bone surface (N.Ob/BS), mineral apposition rate, mineral surface/BS, and bone formation rate/BS, suggesting attenuated bone formation. Decreased angiogenesis was shown by a reduced number of blood vessels in the femur and decreased expression of platelet endothelial cell adhesion molecule (CD31), nerve growth factor, hypoxia-inducible factor-1α, and vascular endothelial growth factor was observed. On the other hand, reduced bone resorption, an effect that could lead to impaired osteogenesis, was demonstrated by lower osteoclast number/BS and decreased tartrate-resistant acid phosphatase and cathepsin K mRNA levels. Reduced number of osteoblasts and decreased expression of receptor activator for nuclear factor-κB ligand could be responsible for compromised bone resorption in T1D mice. In conclusion, T1D mice display reduced bone formation and bone resorption, suggesting decreased bone turnover. Furthermore, this study points to impairments in angiogenesis as a pivotal cause of decreased bone formation.

Bioactivity-based ultra-performance liquid chromatography-coupled quadrupole time-of-flight mass spectrometry for NF-κB inhibitors identification in Chinese Medicinal Preparation Bufei Granule.

Traditional Chinese medicine (TCM) preparations have become effective treatments for many diseases. However, their active ingredients are still uncertain and difficult to identify. In this study, we propose a strategy that integrates ultra-performance liquid chromatography/quadrupole-time-of-flight mass spectrometry (UPLC/Q-TOF-MS) and bioactive (NF-κB inhibitor) luciferase reporter assay systems for the rapid determination of various anti-inflammatory compounds of TCM preparations. In this way, Bufei Granule (BFG), a TCM preparation used for the clinical therapy of asthma, was analyzed by the two ways of component identification and activity detection. Potential anti-inflammatory constituents were screened by NF-κB activity assay systems and simultaneously identified according to the mass spectrometry data. Three structural types of NF-κB inhibitors (caffeic acid derivatives, flavonoids and Pentacyclic triterpenes) were characterized. Further cytokine detection confirmed the anti-inflammatory effects of the potential NF-κB inhibitors. Compared with conventional chromatographic separation and inhibitory activity detection, integrating UPLC/Q-TOF-MS identification and virtual validation was more convenient and more reliable. This strategy clearly demonstrates that MS data-based fingerprinting is a meaningful tool not only in identifying constituents in complex matrix but also in directly screening for powerful trace ingredients in TCM preparations. Copyright © 2016 John Wiley & Sons, Ltd.

Melatonin enhances the in vitro maturation and developmental potential of bovine oocytes denuded of the cumulus oophorus.

This study was designed to determine the effect of melatonin on the in vitro maturation (IVM) and developmental potential of bovine oocytes denuded of the cumulus oophorus (DOs). DOs were cultured alone (DOs) or with 10-9 M melatonin (DOs + MT), cumulus-oocyte complexes (COCs) were cultured without melatonin as the control. After IVM, meiosis II (MII) rates of DOs, and reactive oxygen species (ROS) levels, apoptotic rates and parthenogenetic blastocyst rates of MII oocytes were determined. The relative expression of ATP synthase F0 Subunit 6 and 8 (ATP6 and ATP8), bone morphogenetic protein 15 (BMP-15) and growth differentiation factor 9 (GDF-9) mRNA in MII oocytes and IFN-tau (IFN-τ), Na+/K+-ATPase, catenin-beta like 1 (CTNNBL1) and AQP3 mRNA in parthenogenetic blastocysts were quantified using real-time polymerase chain reaction (PCR). The results showed that: (1) melatonin significantly increased the MII rate of DOs (65.67 ± 3.59 % vs. 82.29 ± 3.92%; P < 0.05), decreased the ROS level (4.83 ± 0.42 counts per second (c.p.s) vs. 3.78 ± 0.29 c.p.s; P < 0.05) and apoptotic rate (36.99 ± 3.62 % vs. 21.88 ± 2.08 %; P < 0.05) and moderated the reduction of relative mRNA levels of ATP6, ATP8, BMP-15 and GDF-9 caused by oocyte denudation; (2) melatonin significantly increased the developmental rate (24.17 ± 3.54 % vs. 35.26 ± 4.87%; P < 0.05), and expression levels of IFN-τ, Na+/K+-ATPase, CTNNBL1 and AQP3 mRNA of blastocyst. These results indicated that melatonin significantly improved the IVM quality of DOs, leading to an increased parthenogenetic blastocyst formation rate and quality.

Combined right hemicolectomy and pancreaticoduodenectomy for locally advanced right hemicolon cancer.

Extracolonic invasion of the duodenum and/or pancreatic head rarely occurs in patients with right hemicolon cancer. However, when necessary, combined radical operation is a challenge to the surgeon. We reported 7 patients with locally advanced right hemicolon cancer who underwent combined right hemicolectomy (RH) and pancreaticoduodenectomy (PD) due to direct involvement of the duodenum or pancreatic head. This study included four males and three females with a mean age of 66.9+/-5.9 years. Computed tomography (CT) scans revealed right hemicolon cancer with duodenal invasion (5 patients) and pancreatic invasion (2). The mean operation time was 410+/-64 minutes and the estimated blood loss was 514+/-157 mL. After the operation, the mean postoperative hospital stay was 22.1+/-7.2 days. Five patients had postoperative complications. The mean follow-up time was 16.4+/-5.9 months. During this period, three patients died from tumor recurrence, one from postoperative complications, one from pulmonary disease, and two survived until the last scheduled follow-up. Five patients survived more than one year. Combined RH and PD for locally advanced right hemicolon cancer can be performed safely, thus providing a long-term survival rate in selected patients in a high-volume center.

Effect of cold-dryness on pulmonary and immunologic function in chronic obstructive pulmonary disease model rats.

OBJECTIVE: To study the effects of cold-dryness on pulmonary and immunologic function of peripheral T-lymphocytes in chronic obstructive pulmonary disease (COPD) model rats, and to provide references for the prevention and treatment of cold-dryness COPD in the Xinjiang region. METHODS: The COPD model was established with an elastase drip into the trachea combined with smoking. The cold-dryness COPD model was developed by stressing with a cold-dry environment. Success of the model was determined by observation of pathologic lung sections. Rats were sacrificed by exsanguination from the femoral artery and changes of peripheral blood CD4+, CD8+, and CD4+/CD8+ were detected by flow cytometry. Data were analyzed with SAS 11.5 statistical software. RESULTS: On the ninetieth day after ending the experiment, Peak expiratory flow in the cold-dryness COPD group was lower than that in the COPD and normal control groups (P < 0.01). The time of inspiration in the cold-dryness COPD group was higher than that in the COPD and normal groups (P < 0.05). Time of expiration (Te) in the cold-dryness COPD group was higher than that in the COPD and normal groups (P < 0.01). 50% tidal volume expiratory flow (EF50) in the cold-dryness COPD group was lower than that in the COPD and normal groups (P < 0.01), and EF50 in the COPD group was lower than that in the normal group (P < 0.05). CD4+ content of peripheral blood in the cold-dryness COPD group was lower than that in the COPD and the normal groups (P < 0.05). CD8+ content in the cold-dryness COPD and COPD groups was higher than that in the normal control group (P < 0.01), and CD8+ content in the cold-dryness COPD group was higher than that in the COPD group (P < 0.01). CD4+/CD8+ in the cold-dryness COPD group and the COPD group was lower than that in the normal control group (P < 0.01), and CD4+/CD8+ in the cold-dryness COPD group was lower than that in the COPD group (P < 0.05). CONCLUSION: In the cold-dryness COPD model, CD8+ increased and CD4+/CD8+ decreased. Moreover, cold-dryness may aggravate this state. The effects of cold-dryness on pulmonary function mainly manifested as prolongation of Te and decrease of EF50, which could be one of causes of cold-dryness environment in the northwest of China leading to COPD with region characteristics.