The involvement of oxidative stress and the TLR4/NF-κB/NLRP3 pathway in acute lung injury induced by high-altitude hypoxia.

OBJECTIVE: This study investigated the effect of oxidative stress and the TLR4/NF-κB/NLRP3 pathway on the pathogenesis of acute lung injury (ALI) induced by high-altitude hypoxia. METHODS: Rats were placed in an animal hyperbaric oxygen chamber to establish a rat model of ALI induced by high-altitude hypoxia after treatment with N-acetylcysteine (NAC; a reactive oxygen species [ROS] inhibitor) or/and MCC950 (an NLPR3 inflammasome inhibitor). After modeling, the wet-to-dry weight ratio (W/D) of rat lung tissues was calculated. In lung tissues, ROS levels were detected with immunofluorescence, the enzyme activity was tested with the kit, and the expression of TLR4/NF-κB/NLRP3 pathway-related genes and proteins was measured with western blotting and qRT-PCR. The levels of inflammatory factors in the serum were quantified with ELISA. RESULTS: After modeling, rats showed significantly increased W/D, ROS levels, and Malondialdehyde (MDA) concentrations and markedly diminished Superoxide dismutase (SOD) and Glutathione (GSH) concentrations in lung tissues (all P < 0.01), accompanied by substantially enhanced serum levels of TNF-α, IL-6, and IL-1ß, significantly reduced serum levels of IL-10, and remarkably augmented TLR4, NLRP3, p-NF-κB p65, NF-κB p65 mRNA, and Caspase-1 expression in lung tissues (all P < 0.01). Furthermore, treatment with NAC or MCC950 alone or in combination prominently lowered the W/D of lung tissues (P < 0.01), serum levels of TNF-α (P < 0.05), IL-6 (P < 0.05), and IL-1ß (P < 0.01), and NF-κB p65 expression and phosphorylation (P < 0.05, P < 0.01) while significantly increasing SOD and GSH concentrations (P < 0.05, P < 0.01) and serum levels of IL-10 (P < 0.01) in modeled rats. Meanwhile, treatment of NAC alone or combined with MCC950 significantly reduced MDA concentration and ROS levels (P < 0.05, P < 0.01) in modeled rats, and treatment of MCC950 alone or combined with NAC considerably declined TLR4, NLRP3, and Caspase-1 expression in modeled rats (P < 0.05, P < 0.01). CONCLUSION: Inhibition of oxidative stress and the TLR4/NF-κB/NLRP3 pathway can ameliorate ALI in rats exposed to high-altitude hypoxia.

OCTA characteristics in non-arteritic central retinal artery occlusion and correlation with visual acuity.

AIM: To observe the retinal and choroidal circulations in patients with non-arteritic permanent central retinal artery occlusion (NA-CRAO) via optical coherence tomography angiography (OCTA) and analyze their correlation with visual acuity. METHODS: Sixty-two eyes with clinically confirmed acute NA-CRAO were included in the study and divided into: A type (mild n=29), B type (moderate n=27) and C type (severe n=6) based on the degree of visual loss, retinal edema, and arterial blood flow delay in fundus fluorescence angiography (FFA). Contralateral healthy eyes were used as the control group. Best-corrected visual acuity (BCVA), slit lamp microscopy, indirect ophthalmoscopy, fundus color photography, OCTA, and FFA were performed. Spearman's correlation analysis was used to determine the correlations between retinal and choroidal vessels and visual acuity. RESULTS: There were no statistically significant differences in age, gender, and intraocular pressure among the three types and the control group (P>0.05). Vessel density in deep capillary plexus (VD-DCP) significantly decreased (P<0.05) in all three types of NA-CRAO patients compared to the control group. Vessel density in superficial vascular plexus (VD-SVP) significantly decreased (P<0.05) in type A patients and choriocapillaris flow area significantly decreased (P<0.05) in type B and type C patients compared to the control group; while outer retinal flow areas significantly increased in the type A (P<0.05) and decreased in type C patients (P<0.05). The retinal thickness significantly increased in type C group (P<0.05). The VD-SVP at fovea in the type A was significantly lower than both of type B and C. The VD-SVP at nasal parafovea in type A and B was significantly lower than type C (P<0.05). The logMAR BCVA of type A was significantly better than that of type B and C groups (P<0.05). Spearman's correlation analysis showed that the logMAR BCVA was positively correlated with VD-SVP at fovea (r=0.679, P=0.031) and nasal parafovea (r=0.826, P=0.013). CONCLUSION: OCTA is valuable for assessing retinal ischemia, and evaluating visual impairment. Deep retinal vasculature is commonly affected in all NA-CRAO types. VD-SVPs at fovea and nasal parafovea can serve as reliable markers of visual impairment in NA-CRAO.

Alpha-fetoprotein upregulates hepatocellular carcinoma cell-intrinsic PD-1 expression through the LATS2/YAP/TEAD1 pathway.

BACKGROUND: Hepatocellular carcinoma (HCC) cell-intrinsic programmed death 1 (PD-1) promotes tumor progression. However, the mechanisms that regulate its expression are unclear. This study investigated the impact of alpha-fetoprotein (AFP) on HCC cell-intrinsic PD-1 expression. METHODS: The expression of PD-1 and AFP at the gene and protein levels was detected using real-time fluorescence quantitative polymerase chain reaction (RT-qPCR) and western blotting (WB). Proteins interacting with AFP were examined by co-immunoprecipitation (CO-IP). Chromatin immunoprecipitation (ChIP) and dual luciferase reporter assays were used to identify transcription-enhanced association domain 1 (TEAD1) binding to the promoter of PD-1. RESULTS: The expression of HCC cell-intrinsic PD-1 was positively correlated with AFP. Mechanistically, AFP inhibited the phosphorylation of large tumor suppressor 2 (LATS2) and yes-associated protein (YAP). As a result, YAP is transferred to the nucleus and forms a transcriptional complex with TEAD1, promoting PD-1 transcription by binding to its promoter. CONCLUSION: AFP is an upstream regulator of the HCC cell-intrinsic PD-1 and increases PD-1 expression via the LATS2/YAP/TEAD1 axis. GENERAL: Our findings provide insight into the mechanisms of HCC development and offer new ideas for further in-depth studies of HCC.

Huangqi Baihe Granules alleviate hypobaric hypoxia-induced acute lung injury in rats by suppressing oxidative stress and the TLR4/NF-κB/NLRP3 inflammatory pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Huangqi Baihe Granules (HQBHG) are a modified formulation based on the traditional recipe "Huangqi Baihe porridge" and the Dunhuang medical prescription "Cistanche Cistanche Soup." The Herbal medicine moistens the lungs and tones the kidneys in addition to replenishing Qi and feeding Yin, making it an ideal choice for enhancing adaptability to high-altitude hypoxic environments. AIM OF THE STUDY: The purpose of this study was to examine a potential molecular mechanism for the treatment and prevention of hypoxic acute lung injury (ALI) in rats using Huangqi Baihe Granules. MATERIALS AND METHODS: The HCP-III laboratory animal low-pressure simulation chamber was utilized to simulate high-altitude environmental exposure and establish an ALI model in rats. The severity of lung damage was evaluated using a battery of tests that included spirometry, a wet/dry lung ratio, H&E staining, and transmission electron microscopy. Using immunofluorescence, the amount of reactive oxygen species (ROS) in lung tissue was determined. Superoxide dismutase (SOD), glutathione (GSH), malondialdehyde (MDA), and myeloperoxidase (MPO) levels in lung tissue were determined using this kit. Serum levels of proinflammatory cytokines, including tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and interleukin-1 beta (IL-1 beta), and antiinflammatory cytokines like interleukin-10 (IL-10) were measured using an enzyme-linked immunosorbent assay kit. Gene expression changes in lung tissue were identified using transcriptomics, and the relative expression of proteins and mRNA involved in the toll-like receptor 4 (TLR4)/nuclear factor-kappa B (NF-κB p65)/Nod-like receptor protein 3 (NLRP3) pathway were determined using western blotting and quantitative real-time PCR. RESULTS: HQBHG was shown to enhance lung function considerably, decrease the wet/dry ratio of the lungs, attenuate lung tissue damage, suppress ROS and MDA formation, and increase SOD activity and GSH expression. The research also demonstrated that HQBHG inhibited the activation of the TLR4/NF-κB p65/NLPR3 signaling pathway in lung tissue, reducing the release of downstream pro-inflammatory cytokines. CONCLUSIONS: HQBHG exhibits potential therapeutic effects against ALI induced by altitude hypoxia through suppressing oxidative stress and inflammatory response. This suggests it may be a novel drug for treating and preventing ALI.

Visual acuity assessment of central retinal artery occlusion patients with or without paracentral acute middle maculopathy via OCT-A.

PURPOSE: The association between paracentral acute middle maculopathy (PAMM) and visual acuity in patients with central retinal artery occlusion (CRAO) is still unclear. The present study investigated the visual acuity of CRAO patients with and without PAMM. METHODS: CRAO patients with PAMM or without PAMM were included. Optical coherence tomography angiography (OCT-A) was used to record the macular retinal thickness and density of shallow and deep vessels. The Best-corrected visual acuity (BCVA) was converted to a logarithm of the minimum angle of resolution (LogMAR) for statistical analysis. RESULTS: There were 34 CRAO patients with PAMM (43.13%), other 30 CRAO patients without PAMM (46.87%). Compared with the no-PAMM group, PAMM group had better LogMAR BCVA (1.48 (0.49, 1.85) Vs. 1.85 (1.70, 1.96), P < 0.01). There was also a significant difference in retinal thickness of the central macular sulcus (328.00 (304.50-332.25) Vs. 352.50 (311.75-420.50), P = 0.01). A significant correlation between LogMAR BCVA and macular retinal thickness was found (r = 0.42; P < 0.01). CONCLUSION: CRAO patients with PAMM had significantly better visual acuity and less macular edema. OCT-A can be used to distinguish different levels of damage due to CRAO.

Non-arteritic anterior ischemic optic neuropathy combined with branch retinal vein obstruction: A case report.

BACKGROUND: Non-arteritic anterior ischemic optic neuropathy (NAION) is an independent disease characterized by edematous optic discs. In eyes with branch retinal vein occlusion (BRVO), the arteries and veins in the ethmoid plate of the optic disc are relatively crowded; however, a combination of the two is clinically uncommon. Herein, we reported a patient with NAION and concealed BRVO, for which the treatment and prognosis were not similar to those for NAION alone. CASE SUMMARY: Herein, we report a case of NAION with concealed BRVO that did not improve with oral medication. A week later, we switched to intravenous drug administration to improve circulation, and the patient's visual acuity and visual field recovered. Hormonal therapy was not administered throughout the study. This case suggested that: (1) Fundus fluorescein angiography (FFA) can help detect hidden BRVO along with the NAION diagnosis; (2) intravenous infusion of drugs to improve circulation has positive effects in treating such patients; and (3) NAION with concealed BRVO may not require systemic hormonal therapy, in contrast with the known treatment for simple NAION. CONCLUSION: NAION may be associated with hidden BRVO, which can only be observed on FFA; intravenous therapy has proven effectiveness.

Association between the triglyceride glucose (TyG) index and the risk of acute kidney injury in critically ill patients with heart failure: analysis of the MIMIC-IV database.

BACKGROUND: Insulin resistance (IR) can be effectively assessed using the dependable surrogate biomarker triglyceride-glucose (TyG) index. In various critical care contexts, like contrast-induced acute kidney injury (AKI), an elevated TyG index has demonstrated a robust correlation with the incidence of AKI. Nonetheless, the potential of the TyG index to predict AKI in critically ill patients with heart failure (HF) remains uncertain. METHODS: A cohort of participants was non-consecutively selected from the Medical Information Mart for Intensive Care IV (MIMIC-IV) database and divided into quartiles based on their TyG index values. The incidence of AKI was the primary outcome. The secondary endpoint was in-hospital mortality within both the whole study population and the subset of AKI patients. The use of the renal replacement therapy (RRT) which represented the progression of AKI severity was also included as a secondary endpoint representing renal outcome. A restricted cubic splines model and Cox proportional hazards models were utilized to evaluate the association of TyG index with the risk of AKI in patients with HF in a critical condition. Kaplan-Meier survival analysis was employed to estimate primary and secondary endpoint disparities across groups differentiated by their TyG index. RESULTS: This study included a total of 1,393 patients, with 59% being male. The incidence of AKI was 82.8%. Cox proportional hazards analyses revealed a significant association between TyG index and the incidence of AKI in critically ill patients with HF. The restricted cubic splines model illustrated the linear relationship between higher TyG index and increased risk of AKI in this specific patient population. Furthermore, the Kaplan-Meier survival analyses unveiled statistically significant differences in the use of RRT across the subset of AKI patients based on the quartiles of the TyG index. CONCLUSIONS: The results highlight the TyG index as a robust and independent predictor of the incidence of AKI and poor renal outcome in patients with HF in a critical condition. However, further confirmation of causality necessitates larger prospective studies.

The effect of aminolevulinic acid hydrochloride topical powder photodynamic therapy versus nocardia rubra cell wall skeleton and observers group in the treatment of cervical low-grade squamous intraepithelial lesions with human papillomavirus infection: A non-randomized study, controlled pilot study.

There are insufficient studies comparing the efficacy of aminolevulinic acid hydrochloride topical powder (ALA) photodynamic therapy (PDT) against Nocardia rubra cell wall skeleton (Nr-CWS) therapy in the treatment of cervical low-grade squamous intraepithelial lesion (LSIL) with human papillomavirus (HPV), especially for long-term efficacy. Patients with cervical LSIL and HPV infection were divided into 3 treatment groups based on their own choice. All patients had a follow-up test including HPV testing, cytology and colposcopy at 4 to 6 months and 12 months after the treatment. Among142 patients, patients received 51 ALA PDT and 41 patients received Nr-CWS. Another 50 patients who refused treatment were included in the Observers group. Four to six months or 12 months after treatment, there was significant difference between 3 groups in the clearance rate of HR-HPV infection and the complete remission (CR) rates of cervical LSIL; the CR rates of cervical LSIL in the ALA PDT group was significantly higher than the Nr-CWS group; but there was no significant difference between 2 groups in the clearance rate of HPV infection. The CR rates of cervical LSIL and the clearance rate of HPV infection in the ALA PDT group was significantly higher than the Observers group; the CR rates of cervical LSIL and the clearance rate of HPV infection in the Nr-CWS group was significantly higher than the Observers group; there was no significant difference in the recurrence rates in ALA PDT and Nr-CWS group after 12 months. Both of ALA PDT and Nr-CWS group had lower recurrence rate than the Observers group. The effect of ALA PDT is similar to Nr-CWS in the clearance rate of HR-HPV infection. Compared to the Nr-CWS group, the CR rates of cervical LSIL were considerably greater in the ALA PDT group. The effect of ALA PDT in the clearance rate of HPV infection and CR rates of cervical LSIL was significantly higher than the follow-up group; Both of ALA PDT and Nr-CWS group had lower recurrence rate than the Observers group. For cervical LSIL with HPV infection, ALA PDT is a very successful therapeutic method that is noninvasive.

Hysteroscopic presentation of endometrial vascular dystrophy: a case report.

Endometrial vascular dystrophy is quite rare, and there is very little literature regarding this subject. We present the unusual case of a 38-year-old woman who experienced vaginal bleeding after menstruation for 3 months. Hysteroscopically, the uterine cavity was filled with tiny, curved blood vessels, the bottom of the cavity was obvious, and polyps were visible. No curved vessels or polyps were identified after curettage. The diagnosis was endometrial hemodystrophy with endometrial polyps. Endometrial vascular dystrophy is a hysteroscopically uncommon benign lesion of the endometrial vessels.

Potentilla anserina polysaccharide alleviates cadmium-induced oxidative stress and apoptosis of H9c2 cells by regulating the MG53-mediated RISK pathway.

Oxidative stress plays a crucial role in cadmium (Cd)-induced myocardial injury. Mitsugumin 53 (MG53) and its mediated reperfusion injury salvage kinase (RISK) pathway have been demonstrated to be closely related to myocardial oxidative damage. Potentilla anserina L. polysaccharide (PAP) is a polysaccharide with antioxidant capacity, which exerts protective effect on Cd-induced damage. However, it remains unknown whether PAP can prevent and treat Cd-induced cardiomyocyte damages. The present study was desgined to explore the effect of PAP on Cd-induced damage in H9c2 cells based on MG53 and the mediated RISK pathway. For in vitro evaluation, cell viability and apoptosis rate were analyzed by CCK-8 assay and flow cytometry, respectively. Furthermore, oxidative stress was assessed by 2',7'-dichlorodihydrofluorescein diacetate (DCFH-DA) staining and using superoxide dismutase (SOD), catalase (CAT), and glutathione/oxidized glutathione (GSH/GSSG) kits. The mitochondrial function was measured by JC-10 staining and ATP detection assay. Western blot was performed to detect the expression of proteins related to MG53, the RISK pathway, and apoptosis. The results indicated that Cd increased the levels of reactive oxygen species (ROS) in H9c2 cells. Cd decreased the activities of SOD and CAT and the ratio of GSH/GSSG, resulting in decreases in cell viability and increases in apoptosis. Interestingly, PAP reversed Cd-induced oxidative stress and cell apoptosis. Meanwhile, Cd reduced the expression of MG53 in H9c2 cells and inhibited the RISK pathway, which was mediated by decreasing the ratio of p-AktSer473/Akt, p-GSK3ßSer9/GSK3ß and p-ERK1/2/ERK1/2. In addition, Cd impaired mitochondrial function, which involved a reduction in ATP content and mitochondrial membrane potential (MMP), and an increase in the ratio of Bax/Bcl-2, cytoplasmic cytochrome c/mitochondrial cytochrome c, and Cleaved-Caspase 3/Pro-Caspase 3. Importantly, PAP alleviated Cd-induced MG53 reduction, activated the RISK pathway, and reduced mitochondrial damage. Interestingly, knockdown of MG53 or inhibition of the RISK pathway attenuated the protective effect of PAP in Cd-induced H9c2 cells. In sum, PAP reduces Cd-induced damage in H9c2 cells, which is mediated by increasing MG53 expression and activating the RISK pathway.

Efficacy and safety of targeted drugs in advanced or metastatic gastric and gastroesophageal junction cancer: A network meta-analysis.

WHAT IS KNOWN AND OBJECTIVE: An increasing number of targeted drugs have been used to treat advanced or metastatic gastric cancer (GC) and gastroesophageal junction cancer (GEJC). However, the optimal treatment efficacy of these drugs is still controversial. The aims of this study are to systematically summarize the efficacy and safety of current targeted drugs for advanced or metastatic GC and GEJC. METHODS: PubMed, EmBase, Cochrane Library, Web of Science and ClinicalTrials were searched for double-blind randomized controlled trials (RCTs) on GC and GEJC up to December 2019. Additionally, we updated the literature search from Jan, 1, 2020 to September 30, 2021. Narrative and quantitative analysis were performed to analyse the efficacy and safety. STATA 15.1 was used to identify publication bias, and the SUCRA (surface under the cumulative ranking) curve was conducted to rank the treatments for each outcome. RESULTS: A total of 27 RCTs with 9295 GC and GEJC patients treated by 19 drugs were included. SUCRA showed that regorafenib was the most likely to improve patients' progression-free survival (96.4%), followed by apatinib (90.7%), nivolumab (82.4%), everolimus (76.5%) and pertuzumab (68.5%). Meanwhile, apatinib (92.4%) was most likely to improve overall survival, followed by nivolumab (87.9%), regorafenib (72.5%), olaparib (67.7%) and lapatinib (63.2%). Additionally, neutropenia, diarrhoea and fatigue were the most common adverse events caused by these drugs, followed by pain, nausea, decreased appetite, anaemia and vomiting. WHAT IS NEW AND CONCLUSION: Regorafenib and nivolumab have higher efficacy and tolerability and are the most advantageous for advanced GC and GEJC. Moreover, apatinib has higher efficacy but lower tolerability. Everolimus and pertuzumab combined with chemotherapy have best secondary higher efficacy for progression-free survival and good tolerability. Lapatinib and olaparib combined with chemotherapy have moderate efficacy for overall survival and good tolerability.

Pinocembrin suppresses proliferation and enhances apoptosis in lung cancer cells in vitro by restraining autophagy.

Lung cancer is one of the leading causes of human death, and the 5-year survival rate for lung cancer patients remains a relative low level. Pinocembrin (Pino) was reported to play an important role in the inhibition of cancer development, so this study was designed to explore the role of pino in lung cancer. A549 cells were treated with different concentration of Pino (25, 50, 100, 150 and 200 µM) for 24, 48 and 72, respectively to detect cell viability by Cell counting kit-8 (CCK-8) assay. Then, the proliferation, apoptosis and autophagy of A549 cells under pino exposure were detected using colony formation, TUNEL and immunofluorescence staining, respectively. Western blot was used to analyze proliferation-, apoptosis-, and autophagy-related proteins. To measure the effects of pino on cell autophagy, the above-mentioned functional assays were conducted again in A549 cells treated with pino and 20 µM autophagy activator rapamycin (RAPA). Declined trends in cell viability, proliferation, and autophagy were found in A549 cells treated with increasing doses of pino, by contrast with those without any treatment. Additionally, the apoptosis of A549 cells was enhanced upon pino exposure, accompanied by elevated caspase3 activity. However, RAPA reversed the anti-proliferative, anti-autophagic and pro-apoptotic properties of pino in A549 cells. In conclusion, this paper is the first to verify that pino suppresses the proliferation and enhances the apoptosis of lung cancer cells by restraining autophagy, indicating that pino has potential therapeutic effects on the treatment of lung cancer.

Isorhamnetin Promotes MKN-45 Gastric Cancer Cell Apoptosis by Inhibiting PI3K-Mediated Adaptive Autophagy in a Hypoxic Environment.

A tumor-related hypoxic microenvironment can promote the proliferation of gastric cancer cells, and hypoxic-induced autophagy is the main mechanism of protection against hypoxia in gastric cancer cells. Isorhamnetin (ISO) is a chemical substance derived from plants, mainly from the sea buckthorn. Previous studies have shown that ISO has antitumor effects, but the effects of ISO against gastric cancer in a hypoxic environment are still unknown. In this study, we investigated the effects of ISO against gastric cancer in a hypoxic environment and the mechanisms underlying ISO-induced gastric cancer cell death. The results show that ISO targeted PI3K and blocked the PI3K-AKT-mTOR signaling pathway, significantly inhibiting gastric cancer cell autophagy in a hypoxic environment, inhibiting cell proliferation, decreasing mitochondrial membrane potential, and promoting mitochondria-mediated apoptosis. ISO, a functional food component, is a promising candidate for the treatment of gastric cancer.

Analysis of Macular Microperimetry Characteristics in Non-Arteritic Anterior Ischemic Optic Neuropathy.

BACKGROUND The aim of this study was to analyze the correlation of macular micro-field characteristics with vision and visual field in patients with non-arteritic anterior ischemic optic neuropathy. MATERIAL AND METHODS Retrospective case analysis was performed. Fifty-eight NAION patients with 62 affected eyes were included in the study. In addition, 54 eyes not affected by NAION from 54 patients among the 58 patients were included as controls. All eyes underwent best corrected visual acuity (BCVA) test, slit lamp biomicroscopy, indirect ophthalmoscopy, visual field examination, and microperimetry. BCVA was converted into logarithm of minimum angle of resolution (LogMAR) for statistical analysis. There was no significant difference in age, sex, eye type, or intraocular pressure between the 2 groups. The macular integrity assessment (MAIA) instrument was used for microperimetry. Mean light sensitivity (microMS) in the 10° macular region and the fixation rates for macular fovea 2° and 4° were recorded. Spearman correlation analysis was performed. RESULTS The microMS values were significantly different between the control group and the affected eye group (t=-2.427, P=0.036). MicroMS was significantly correlated with logMAR BCVA (r=-0.802, P=-0.005) and with mean sensitivity (MS) and mean deviation (MD) (r=0.912, P=0.002; r=-0.905, P=0.002; P<0.05). MS and MD were not correlated with logMAR BCVA (r=-0.465, P=0.245; r=0.437, P=0.278). CONCLUSIONS The present study demonstrates that microMS of macular micro-visual field in NAION patients was significantly decreased at early stage, and was significantly correlated with and consistent with visual acuity and visual field.

The use of clozapine is protective for low bone mineral density induced by prolactin-raising antipsychotics in inpatients with schizophrenia.

Low bone mineral density (BMD) is common among patients with schizophrenia; however, the pathogenesis is still unclear. Different types of antipsychotics may have different effects on BMD in inpatients with schizophrenia. INTRODUCTION: This retrospective study aimed to evaluate the effects of prolactin-raising (PR) antipsychotics vs. clozapine combined with PR antipsychotics on BMD of patients with schizophrenia and analyzed clinically related factors that may affect BMD. METHODS: A total of 125 participants (males/females = 62/63) were included. Patients were treated with PR antipsychotics vs. clozapine combined with PR antipsychotics. They were similar in demographic and clinical characteristics. BMD was examined in their lumbar spine and proximal femur by a dual-energy X-ray (DEXA) absorption measurement device. Laboratory variables (including blood levels of prolactin, estradiol, testosterone, and cortisol) were collected. RESULTS: Among 125 inpatients with schizophrenia, the prevalence of osteoporosis and low BMD (including osteoporosis and osteopenia) was 26.4% and 64%. The average BMD T value in patients receiving clozapine combined with PR antipsychotics was significantly higher than in patients receiving PR antipsychotics (p < 0.05). Patients in the clozapine combined with PR antipsychotic group had higher testosterone levels than the PR antipsychotic group (Z = - 2.77, p = 0.006). Linear logistic regression analysis indicated that clozapine combined with PR antipsychotic treatment (p < 0.05) and higher estradiol level (p < 0.05) may be significantly associated with higher BMD. CONCLUSIONS: Our results suggest that the use of clozapine may be a protective factor for low BMD induced by PR antipsychotics in inpatients with schizophrenia. The possible mechanism is that clozapine may protect BMD by regulating estrogen and testosterone levels, but the mechanism by which clozapine regulates these two sex hormones needs further investigation.

Detection and Quantification of Total and Pathogenic Vibrio parahaemolyticus in Anadara subcrenata in the Zhoushan Archipelago.

This study aimed to investigate the prevalence of total and pathogenic Vibrio parahaemolyticus in Anadara subcrenata sampled from aquafarms and retail markets in the Zhoushan islands during June 2013 to March 2015, using the most probable number-polymerase chain reaction (MPN-PCR) method. Total V. parahaemolyticus was detected in 265 (83.86%) samples with the density 0.3 to 2400 MPN/g. In total, 30.70% and 17.41% of the samples exceeded 100 MPN/g and 1,000 MPN/g, respectively. Both highest positive rate (98.99%) and highest prevalence (median = 210.0 MPN/g) were recorded in summer. Samples from aquafarms had a higher positive rate and median than those from retail markets. Pathogenic V. parahaemolyticus was detected both in aquafarms and retail markets in all seasons but not in winter. Among the 265 tlh-positive samples, 20 (7.55%) of the samples harbored tdh, and 5 (1.89%) of the samples harbored both tdh and trh. These results indicate that the Zhoushan archipelago is severely contaminated with V. parahaemolyticus in Anadara subcrenata; these results are applicable in risk assessment and to control the risk of food-borne disease caused by V. parahaemolyticus.

Astragalus Polysaccharide Eases G1 Phase-Correlative Bystander Effects through Mediation of TGF- ß R/MAPK/ROS Signal Pathway After Carbon Ion Irradiation in BMSCs.

Although Astragalus polysaccharide (APS) has been shown to have various pharmacological effects, there have been no studies concerning the inhibitory effects of APS on the radiation-induced bystander effects (RIBE). The aim of this study was to investigate whether APS could suppress RIBE damage by inhibiting cell growth, micronucleus (MN) formation and 53BP1 foci number increased in bone marrow mesenchymal stem cells (BMSCs), named bystander cells, as well as to explore its mechanism. In this study, APS decreased proliferation and colony rate of bystander cells by inducing cell cycle arrest at G1 phase via extrinsic and intrinsic DNA damage. Regarding mechanism, APS inhibited mitogen-activated protein kinase (MAPK) signal pathway by down-regulating the expression of the key proteins, phosphorylated JNK (p-JNK), phosphorylated ERK (p-ERK) but not phosphorylated P38 (p-P38), and down-regulating their downstream function protein and molecule, cyclooxygenase-2 (COX-2) and reactive oxygen species (ROS). Moreover, in bystander cells, APS inhibits expression of transforming growth factor ß receptor II (TGF- ß R II), a cell membrane receptor, resulting in lower ROS production and secretion via TGF- ß R-JNK/ERK-COX-2/ROS not P38 signaling. They gave a hint that the decreased RIBE damage induced by APS treatment involved TGF- ß R-JNK/ERK-COX-2/ROS down-regulation.

Dual Energy Spectral CT Imaging in the assessment of Gastric Cancer and cell proliferation: A Preliminary Study.

Gastric cancer is one of the main diseases leading to cancer-related death. The recently introduced dual-energy spectral CT (DEsCT), allows to obtain many quantitative measurements from iodine-based material decomposition (MD) images, which contribute to improve the accuracy of staging of GC comparing to multidetector spiral CT. And Ki-67 is a well-recognized nuclear antigen-specific biomarker reflecting cellular proliferation for estimating growth fractions of various tumor types. In the present study we analyzed the features of quantitative measurements (the curve slope (λHU), IC, normalized iodine concentrations (NIC)) obtained from DEsCT and levels of Ki-67 protein expression. We demonstrated that the values between advanced gastric cancer (AGC) and early gastric cancer (EGC) were significantly different both in venous phase (VP) and delayed phase (DP). The values of different level of Ki-67 expression grade were significantly different both in VP and DP. The rank correlation analysis between Ki-67 grade and IC, NIC and λHU values showed significantly positive correlation in VP and DP. These results suggested that quantitative parameters (IC, NIC and λHU) in dual-energy CT imaging can be used to differentiate EGC from AGC, and have significantly positive correlation with Ki-67 antigen expression levels in gastric cancer for indicating tumor cellular proliferation.

Manifestations of central retinal artery occlusion revealed by fundus fluorescein angiography are associated with the degree of visual loss.

The aim of this study was to investigate the association between central visual impairment and the characteristics of fundus fluorescein angiography (FFA) in patients with central retinal artery occlusion (CRAO). A total of 63 patients were diagnosed with CRAO by FFA. The visual dysfunction was classified into severe, mild and light degrees. Tropicamide was administered for mydriasis. FFA examination was performed using Heidelberg retinal tomography. The associations of age, gender and disease course with CRAO type were analyzed. Three types of manifestations were identified by FFA in 63 eyes, including poor perfusion (18 cases), exudation (22 cases) and mixed types (23 cases) of CRAO. No significant difference was found in age (F=0.171, P=0.844) and disease course (F=0.016, P=0.984) among the three types of CRAO. Similarly, no significant difference was found in gender among the three types of CRAO (χ2=0.176, P=0.916). The damage to vision caused by the exudation type of CRAO was not as severe as that caused by the poor perfusion and mixed types of CRAO. The distributions of damage severity caused by the poor perfusion and mixed types of CRAO were similar. In conclusion, the FFA observations for CRAO can be classified into three types of manifestations. The damage to vision in patients with CRAO is likely to be associated with poor perfusion in the retinal artery rather than exudation affecting the retina or optic disc. The patterns of clinical manifestations are not associated with age, gender or disease course.