The STING inhibitor C-176 attenuates osteoclast-related osteolytic diseases by inhibiting osteoclast differentiation.

Inflammatory osteolysis occurs primarily in the context of osteoarthritis, aseptic inflammation, prosthesis loosening, and other conditions. An excessive immune inflammatory response causes excessive activation of osteoclasts, leading to bone loss and bone destruction. The signaling protein stimulator of interferon gene (STING) can regulate the immune response of osteoclasts. C-176 is a furan derivative that can inhibit activation of the STING pathway and exert anti-inflammatory effects. The effect of C-176 on osteoclast differentiation is not yet clear. In this study, we found that C-176 could inhibit STING activation in osteoclast precursor cells and inhibit osteoclast activation induced by nuclear factor κB ligand receptor activator in a dose-dependent manner. After treatment with C-176, the expression of the osteoclast differentiation marker genes nuclear factor of activated T-cells c1(NFATc1), cathepsin K, calcitonin receptor, and V-ATPase a3 decreased. In addition, C-176 reduced actin loop formation and bone resorption capacity. The WB results showed that C-176 downregulated the expression of the osteoclast marker protein NFATc1 and inhibited activation of the STING-mediated NF-κB pathway. We also found that C-176 could inhibit the phosphorylation of mitogen-activated protein kinase signaling pathway factors induced by RANKL. Moreover, we verified that C-176 could reduce LPS-induced bone absorption in mice, reduce joint destruction in knee arthritis induced by meniscal instability, and protect against cartilage matrix loss in ankle arthritis induced by collagen immunity. In summary, our findings demonstrated that C-176 could inhibit the formation and activation of osteoclasts and could be used as a potential therapeutic agent for inflammatory osteolytic diseases.

The effect of China's birth policy changes on birth defects-A large hospital-based cross-sectional study.

A retrospective analysis of birth data hospital-based obtained from 14 monitoring areas in the Huaihe River Basin from 2009 to 2019 was conducted. Trend in the total prevalence of birth defects (BDs) and subgroups were analyzed using the Joinpoint Regression model. The incidence of BDs increased gradually from 118.87 per 10,000 in 2009 to 241.18 per 10,000 in 2019 (AAPC = 5.91, P < 0.001). Congenital heart diseases were the most common subtype of BDs. The proportion of maternal age younger than 25 decreased but the age 25-40 years increased significantly (AAPC<20=-5.58; AAPC20-24=-6.38; AAPC25-29 = 5.15; AAPC30-35 = 7.07; AAPC35-40 = 8.27; All P < 0.05). Compared with the one-child policy period, the risk of BDs was greater for groups among maternal age younger than 40 years during the partial and universal two-child policy period (P < 0.001). The incidence of BDs and the proportion of women with advanced maternal age in Huaihe River Basin is increasing. There was an interaction between changes in birth policy and the mother's age on the risk of BDs.

Luteolin alleviates ulcerative colitis through SHP-1/STAT3 pathway.

BACKGROUND: Previous studies have demonstrated that Luteolin has a positive effect on epithelial barrier integrity by promoting the function of tight protein, however, little is known about the underline mechanism of Luteolin. In this study, we constructed Caco-2 cell monolayer to explore the effects and the regulation mechanism of Luteolin in intestinal epithelial barrier integrity. METHODS: Caco-2 cells were co-treated with TNF-α, Interferon-γ (IFN-γ) and Luteolin for 24 h. Overexpression or knockdown of SHP-1 was applied to study the effects of protein phosphoserine phosphatase-1 (SHP-1) on epithelial barrier integrity. Cell viability was tested by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Barrier function was detected by trans-epithelial electrical resistance (TEER) and FITC-dextran assay. The expression levels of SHP-1, phosphorylation signal transducer and activator of transcription 3 (p-STAT3), STAT3 and tight junction proteins were measured by qRT-PCR or western blot. In vivo model of ulcerative colitis was established to detect the function of Luteolin in ulcerative colitis. RESULTS: We clarified that Luteolin protected intestinal epithelial barrier function of Caco-2 monolayers by increasing the resistance values and tight junction (TJ) protein expression. The expression of OCLN, CLDN1, and ZO1 was increased by Luteolin, while the expression of CLDN2 was decreased. Furthermore, Luteolin significantly alleviated the symptom of ulcerative colitis in DSS-induced mice. The in vitro cell model proved that overexpression of SHP-1 promotes the epithelial barrier function and knockdown of SHP-1 or STAT3 activation destroyed the protective effects of Luteolin on the expression of TJ proteins. CONCLUSION: We found that the treatment of Luteolin promoted epithelial barrier function and Luteolin might preserve intestinal epithelial barrier function through suppression of STAT3 signaling pathway by SHP-1.

Unilateral contrast-induced encephalopathy with contrast medium exudation: A case report.

BACKGROUND: Contrast-induced encephalopathy (CIE) is a rare transient, reversible abnormality in the structure or function of the nervous system caused by the intravascular use of contrast agents. CIE can present with a range of neurological manifestations, including focal neurological deficits (hemiplegia, hemianopia, cortical blindness, aphasia, and parkinsonism) and systemic symptoms (confusion, seizures, and coma). However, if not accurately diagnosed and treated in a timely manner, CIE can cause irreversible damage to patients, especially critically ill patients. CASE SUMMARY: A male in his 50 s, 2 h after digital subtraction angiography, had a progressive disorder of consciousness, mixed aphasia, bilateral pupillary sluggish light reflex, and right limb weakness. Seven hours after the procedure, he developed unconsciousness, high fever (39.5 °C), seizures, hemiplegia, neck stiffness (+), and right Babinski signs (+). computed tomography (CT) findings 2 h postprocedure were very confusing and led us to misdiagnose the patient with subarachnoid hemorrhage. Brain CT was performed again 7 h after the procedure. Compared with the CT 2 h after the procedure, the CT 7 h after the procedure showed that the manifestations of subarachnoid hemorrhage in the left cerebral hemisphere had disappeared and were replaced by brain tissue swelling, and the cerebral sulci had disappeared. Combined with the clinical manifestations of the patient and after the exclusion of subarachnoid hemorrhage and cerebrovascular embolism, we diagnosed the patient with CIE, and intravenous fluids were given for adequate hydration, as well as mannitol, albumin dehydration, furosemide and the glucocorticoid methylprednisolone. After 17 d of active treatment, the patient was discharged with no sequelae. CONCLUSION: CIE should be taken seriously, but it is easily misdiagnosed, and once CIE is diagnosed, rapid, accurate diagnosis and treatment are critical steps. Whether a follow-up examination using a contrast agent can be performed should be closely evaluated, and the patient should be fully informed of the associated risks.

Pseudocryphonectriaelaeocarpicola gen. et sp. nov. (Cryphonectriaceae, Diaporthales) causing stem blight of Elaeocarpus spp. in China.

Cryphonectriaceae is a diaporthalean family containing important plant pathogens of which Cryphonectriaparasitica is the most notorious one. An emerging stem blight disease on Elaeocarpusapiculatus (Elaeocarpaceae) and E.hainanensis was observed in Guangdong Province of China recently. Typical Cryphonectria blight-like symptoms including cankers on tree barks with obvious orange conidial tendrils were observed. Forty-eight isolates were obtained from diseased tissues and conidiomata formed on the hosts E.apiculatus and E.hainanensis. These isolates were further identified based on both morphology and molecular methods using the combined sequence data of the internal transcribed spacer (ITS) region, large subunit of the nrDNA (LSU), the translation elongation factor 1-alpha (tef1) and DNA-directed RNA polymerase II second largest subunit (rpb2) genes. As a result, the fungus represents an undescribed genus and species within the family Cryphonectriaceae. Hence, Pseudocryphonectriaelaeocarpicola gen. et sp. nov. is proposed herein to represent these isolates from diseased barks of E.apiculatus and E.hainanensis. Pseudocryphonectria differs from the other genera of Cryphonectriaceae in having dimorphic conidia. Further inoculation results showed that P.elaeocarpicola is the causal agent of this emerging blight disease in China, which can quickly infect and kill the hosts E.apiculatus and E.hainanensis.

Metarhizium Entomopathogenic Fungi Against the Beetle Brontispa longissima (Coleoptera: Hispidae): Isolation and Species Identification.

Seven entomopathogenic fungi strains (M1-7) were isolated from field-obtained dead coconut hispine beetles Brontispa longissima (Gestro), identified to species, and bioassayed for their pathogenicity. According to ITS sequences, all isolates belong in the genus Metarhizium, mainly M. flavoviride and M. anisopliae. Measured median lethal times (LT50) of 1×107 conidia/ml of M1-7 against fourth-instar B. longissima larvae within 15 d following exposure were, respectively: 5.43, 10.64, 11.26, 10.93, 6.62, 4.73, and 5.95 d. The isolate M6 yielded the highest mortality to fourth-instar larvae, and was thus selected to be tested against other larval instars and adults of B. longissima, after Time-Dose-Mortality (TDM) models. M6 proved more pathogenic against larvae than adults. The obtained bioassays data produced a good fit to the TDM models, yielding estimated LC50 and LT50 for each of the tested developmental stages of B. longissima. Both the obtained dose (ß) and time effect (ri) parameters from TDM models suggest that first-instar larvae are the most susceptible life stage of the pest insect, while adults are more resistant to M6 infection. Calculated LC50 values were, respectively, 1.23×103 and 1.15×106 conidia/ml for first-instar larvae and adults, on the 15th day following M6 inoculation. Estimated LT50 were 3.3 and 5.9 d for first-instar larvae and adults, respectively, at 1×108 conidia/ml. Taken together, these results would suggest Metarhizium M6 as an option for the biological control of B. longissima in the field.

Management and implementation strategies of pre-screening triage in children during coronavirus disease 2019 pandemic in Guangzhou, China.

BACKGROUND: Emerging infectious diseases are a constant threat to the public's health and health care systems around the world. Coronavirus disease 2019 (COVID-2019), which was defined by the World Health Organization as pandemic, has rapidly emerged as a global health threat. Outbreak evolution and prevention of international implications require substantial flexibility of frontline health care facilities in their response. AIM: To explore the effect of the implementation and management strategy of pre-screening triage in children during COVID-19. METHODS: The standardized triage screening procedures included a standardized triage screening questionnaire, setup of pre-screening triage station, multi-point temperature monitoring, extensive screenings, and two-way protection. In order to ensure the implementation of the pre-screening triage, the prevention and control management strategies included training, emergency exercise, and staff protection. Statistical analysis was performed on the data from all the children hospitalized from January 20, 2020 to March 20, 2020 at solstice during the pandemic period. Data were obtained from questionnaires and electronic medical record systems. RESULTS: A total of 17561 children, including 2652 who met the criteria for screening, 192 suspected cases, and two confirmed cases without omission, were screened from January 20, 2020 to March 20, 2020 at solstice during the pandemic period. There was zero transmission of the infection to any medical staff. CONCLUSION: The effective strategies for pre-screening triage have an essential role in the prevention and control of hospital infection.

Ligustilide protects PC12 cells from oxygen-glucose deprivation/reoxygenation-induced apoptosis via the LKB1-AMPK-mTOR signaling pathway.

Autophagy has been shown to have a protective effect against brain damage. Ligustilide (LIG) is a bioactive substance isolated from Ligusticum chuanxiong, a traditional Chinese medicine. LIG has a neuroprotective effect; however, it is unclear whether this neuroprotective effect involves autophagy. In this study, PC12 cells were treated with 1 × 10-5-1 × 10-9 M LIG for 0, 3, 12 or 24 hours, and cell proliferation was evaluated using the 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) assay. Treatment with 1 × 10-6 M LIG for 3 hours had the greatest effect on cell proliferation, and was therefore used for subsequent experiments. PC12 cells were pre-treated with 1 × 10-6 M LIG for 3 hours, cultured in 95% N2/5% CO2 in Dulbecco's modified Eagle's medium without glucose or serum for 4 hours, and then cultured normally for 16 hours, to simulate oxygen-glucose deprivation/reoxygenation (OGD/R). Cell proliferation was assessed with the MTS assay. Apoptosis was detected by flow cytometry. The expression levels of apoptosis-related proteins, Bcl-2 and Bax, autophagy-related proteins, Beclin 1 and microtubule-associated protein l light chain 3B (LC3-II), and liver kinase B1 (LKB1)-5'-adenosine monophosphate-activated protein kinase (AMPK)-mammalian target of rapamycin (mTOR) signaling pathway-related proteins were assessed by western blot assay. Immunofluorescence staining was used to detect LC3-II expression. Autophagosome formation was observed by electron microscopy. LIG significantly decreased apoptosis, increased Bcl-2, Beclin 1 and LC3-II expression, decreased Bax expression, increased LC3-II immunoreactivity and the number of autophagosomes, and activated the LKB1-AMPK-mTOR signaling pathway in PC12 cells exposed to OGD/R. The addition of the autophagy inhibitor 3-methyladenine or dorsomorphin before OGD/R attenuated the activation of the LKB1-AMPK-mTOR signaling pathway in cells treated with LIG. Taken together, our findings show that LIG promotes autophagy and protects PC12 cells from apoptosis induced by OGD/R via the LKB1-AMPK-mTOR signaling pathway.

New records of Celoporthe guangdongensis and Cytospora rhizophorae on mangrove apple in China.

BACKGROUND: Sonneratia apetala Francis Buchanan-Hamilton (Sonneratiaceae, Myrtales), is a woody species with high adaptability and seed production capacity. S. apetala is widely cultivated worldwide as the main species for mangrove construction. However, the study of diseases affecting S. apetala is limitted, with only a few fungal pathogens being recorded. Cryphonectriaceae (Diaporthales) species are the main pathogens of plants. They can cause canker diseases to several trees and thereby seriously threaten the health of the hosts. These pathogens include Cryphonectria parasitica (Cryphonectriaceae) causing chestnut blight on Castanea (Rigling and Prospero 2017) and Cytospora chrysosperma (Cytosporaceae) causing polar and willow canker to Populus and Salix (Wang et al. 2015) . Therefore, the timely detection of of Cryphonectriaceae canker pathogens on S. apetala is extremely important for protecting the mangrove forests. NEW INFORMATION: Two diaporthalean fungi, Celoporthe guangdongensis and Cytospora rhizophorae have been reported for the first time to cause canker on the branches of S. apetala. C. guangdongensis is significantly pathogenic and C. rhizophorae is saprophytic on S. apetala.

[Protective effects of sini decoction on adriamycin-induced heart failure and its mechanism].

OBJECTIVE: To investigate the protective effects of Sini decoction (SND) on Adriamycin-induced heart failure and its mechanism. METHODS: SD rats were randomly divided into three groups:control group,heart failure model group and SND group. ADR was injected in to the rats of model group and SND group by caudal vein. After injection,the rats in SND group were given SND [3.75 g/(kg x d), p.o.]. Three weeks later, protein expressions of Bid and Bcl-xl were detected by immunohistochemistry; mRNA expression ratio of Bcl-xl/Bcl-xs was detected by RT-PCR and apoptosis rate was determinated by flow cytometry. RESULTS: Compared with control group, the protein expression of Bcl-xl and mRNA ratio of Bcl-xl/Bcl-xs obviously decreased,while the protein expression of Bid and apoptosis rate significantly increased in the model group. SND could decrease cell apoptosis, increase the protein expression of Bcl-xl, increase bcl-xl/bcl-xs mRNA ratio and decrease Bid protein expression. CONCLUSION: Bcl-xl may play an important role in ADR-induced heart failure rats. The mechanism of SND on protecting cardiocyte may be related to apoptosis correlation factor, Bcl-xl and Bid.

[Study on activity and mechanism of Sini Decoction anti-mitochondrial oxidation injury caused by myocardial ischemia/reperfusion].

OBJECTIVE: To study the activity and mechanism of Sini Decoction (SND) Anti-mitochondrial Oxidation Injury caused by Myocardial Ischemia/Reperfusion. METHODS: Kun ming mice were randomly divided into three groups: Control group, Ischemia/Reperfusion (I/R) group and SND-treated group. At the end of experiment,hearts of mice were taken out for further detection. Activity of myocardium and mitochondrial SOD, content of myocardium and mitochondrial MDA, swelling of mitochondria, Lactic Acid content of myocardium and MnSODmRNA expression were observed. RESULTS: SND could increase the activity of myocardium and mitochondrial SOD (P<0.01), decrease the content of myocardium and mitochondrial MDA (P<0.01), decrease the Lactic Acid content of myocardium, lighted the swelling of mitochondria (P<0.01) and change the expression of MnSODmRNA (P<0.01). CONCLUSION: Sini decoction can anti-mitochondrial oxidation injury caused by Myocardial Ischemia/Reperfusion, its mechanism may be relate to increasing the MnSODmRNA expression.

[Industrial ecological development of Jilin Province, Northeast China based on structure optimization vision.] / 基于结构调整视角的吉林省产业生态化发展.

Based on the interactive coercing mechanism between the industrial system and the ecosystem, we evaluated Jilin's ecologicalization of industrial structure, employing the systematic ana-lysis method and the comprehensive index evaluation method, and explored the spatio-temporal cha-racteristics.The result showed that the ecological level of industrial structure as well as the industrial structure optimization and resource-environmental efficiency had been significantly improved in 2000-2013. The regional difference showed a trend of resource-environmental efficiency > industrial structure optimization > ecologicalization of industrial structure. Spatially, it demonstrated a "higher in west, lower in east" pattern, and at city scale, it showed a decreasing trend from the core (Changchun) to outside. According to the coordination of industrial structure optimization and resource-environmental efficiency, we categorized the nine cities in Jilin Province into four ecologica-lization types: high coordination type, low coordination type, economic development ahead, and ecological development ahead.

[Study on the relationship between blood stasis syndrome and clinical pathology in patients with IgA nephropathy].

OBJECTIVE: To explore the relationship between blood stasis Syndrome and clinical pathological parameters in patients with IgA nephropathy (IgAN). METHODS: The clinicopathological data were analyzed of 94 IgAN patients of traditional Chinese medicine blood stasis syndrome. RESULTS: Of the 94 IgAN patients, 61.70% had blood stasis syndrome (BS) and 38.30% had non- blood stasis syndrome (non-BS). In patients with BS, dark purple tongue proper was the symptom most commonly seen; the clinical manifestations were mostly proteinuria with hematuria, often accompanied with hypertension and renal dysfunction. Compared with those in patients without BS, plasma levels of serum creatinine (SCr), triglyceride (TG) and plasma fibrinogen (FIB) were obviously higher, activated partial thromboplastin time (APTT), and urokinase-type plasminogen activators (u-PA) significantly lower; and scores of glomerular sclerosis, tubular interstitial lesions, interstitial inflammatory cell infiltration, interstitial fibrosis, tubular atrophy and vascular sclerosis significantly higher. Besides, the Lee's grades in them of III - V were mostly seen. CONCLUSION: Blood stasis syndrome of IgAN are correlated with certain clinical parameters and severity of renal pathological changes. The combination of TCM holistic syndrome differentiation and modern medicinal micro-differentiation is more favorable for making clear the nature of blood stasis Syndrome of IgAN.

[Protective effects of Sini decoction on adriamycin-induced heart failure and its mechanism: role of superoxide dismutase].

OBJECTIVE: To investigate the role of superoxide dismutase (SOD) in Adriamycin (ADR)-induced heart failure and the protective effects of Sini decoction (SND). METHOD: SD rats were randomly divided into three groups, control group, heart failure group and SND group. ADR was injected in the rats of heart failure group and SND group by caudal vein. After injection, the rats in SND group were given SND (3.75 g x kg(-1) x d(-1), p.o.). Three weeks later, cardiac function, content of malondialdehyde (MDA) of both myocardium and mitochondria and activity of Cu-Zn SOD and Mn SOD were measured. The mRNA expression of Cu-Zn SOD and Mn SOD were also detected by RT-PCR. RESULT: Compared with control group, LVSP and +/- dp/dt max were obviously decreased, while LVEDP was markedly increased in the heart failure group. The mRNA expression and the activity of Cu-Zn SOD and Mn SOD in heart failure group were obviously lower than that in the controls'. In addition, the MDA content of both myocardium and mitochondria were clearly increased in heart failure rats. In SND-treated rats, the cardiac function, the activity and the mRNA expression of Cu-Zn SOD and Mn SOD were significantly elevated and the content of MDA was reduced, which had no statistic difference with the rats in control group. CONCLUSION: The data suggest that oxidative stress is present in the mitochondria of myocardium in ADR-induced heart failure rats and it can be eased by SND. The mechanism may be closely related to SOD.

[Effect of lipopolysaccharide on expression of interleukin-6 in human synoviocyte from patients with rheumatoid arthritis].

AIM: To study the effects of lipopolysaccharide (LPS), the supernatant of U937 cells stimulated with LPS and dexamethasone on interleukin-6 (IL-6) expression in the synoviocyte from patients with rheumatoid arthritis (RA). METHODS: Fibroblast-like synoviocytes (FLS) from the joint tissue of patients with rheumatoid arthritis were cultured and incubated for 24 h with LPS (1 mg.L-1) or the supernatant of U937 cells stimulated with LPS (1 mg.L-1) for 24 h. Dexamethasone was added to the supernatant of U937 cells and FLS was incubated for 24 h. The expression of IL-6 protein was detected by radioimmunoassay. The mRNA expression of IL-6 was accessed by RT-PCR. RESULTS: The growth of FLS was not markedly affected by LPS, and the protein secretion and mRNA expression of IL-6 were not markedly changed in FLS treated with LPS. The IL-6 secretion and IL-6 mRNA expression were significantly increased in FLS cultured with the supernatant from U937 cell treated with LPS. Dexamethasone markedly inhibited the protein secretion and mRNA expression of IL-6 in FLS cultured with the supernatant from U937 cell stimulated with LPS. The inhibitory effects were increased as the concentration of dexamethasone increased. CONCLUSION: LPS was not shown to directly affect the expression of IL-6 in FLS, but it indirectly causes the increase of the IL-6 expression in FLS by stimulating U937 cell. Dexamethasone can inhibit this increase of the IL-6 expression.

[Effect of lipopolysaccharide on expression of matrix metalloproteinase-9 in human synoviocyte from patients with rheumatoid arthritis].

AIM: To study the effects of lipopolysaccharide (LPS), the supernatant of U937 cells stimulated with LPS and dexamethasone on matrix metalloproteinase-9 (MMP-9) expression in the synoviocyte from patients with rheumatoid arthritis(RA). METHODS: Fibroblast-like cells (FLS) from the joint tissue of patients with rheumatoid arthritis were cultured and incubated for 24 h with LPS (1 mg.L-1) or the supernatant of U937 cells stimulated with LPS (1 mg.L-1) for 24 h. Dexamethasone was added to the supernatant of U937 cells and FLS was incubated for 24 h. The activity of MMP-9 was analyzed by gelatin zymography. Protein expression of MMP-9 was detected by Western blot using special polyclonal antibodies. The mRNA expression of MMP-9 was detected by RT-PCR. RESULTS: The expression of MMP-9 was not markedly changed in FLS treated with LPS. The MMP-9 activity, MMP-9 secretion and MMP-9 mRNA expression were significantly increased in FLS cultured with the supernatant from U937 cell treated with LPS. Dexamethasone markedly inhibited the activity, protein secretion and mRNA expression of MMP-9 in FLS cultured with the supernatant from U937 cell stimulated with LPS, and the inhibitory effects were increased as the concentration of dexamethasone increased. CONCLUSION: LPS did not directly affect the expression of MMP-9 in FLS, but it was found to indirectly cause the increase of MMP-9 expression in FLS by stimulating U937 cell. Dexamethasone was found to inhibit this increase of MMP-9 expression.

[Effect of indomethacin on expression of interleukin-6 caused by lipopolysaccharide in rheumatoid arthritic patients' synoviocyte].

AIM: To study the effects of indomethacin on interleukin-6 (IL-6) expression stimulated with lipopolysaccharide (LPS) in rheumatoid arthritic patients' synoviocyte. METHODS: Fibroblast-like cells (FLS) from rheumatoid arthritic patients' joint tissue were cultured for 24 h and incubated 24 h with LPS (1 mg.L-1) or the supernatant of U937 cells stimulated by LPS (1 mg.L-1). After indomethacin or dexamethasone added into the supernatant of U937 cells, FLS was incubated with the super natant for 24 h. The expression of IL-6 protein was detected by radioimmunoassay. The mRNA expression of IL-6 was accessed by RT-PCR. RESULTS: LPS did not obviously affect the growth of FLS, and the protein secretion and mRNA expression of IL-6 were not changed in FLS treated with LPS. The IL-6 secretion and IL-6 mRNA expression were significantly increased in FLS cultured with the supernatant from U937 cell treated with LPS. Indomethacin at concentrations of 1 x 10(-7)-1 x 10(-5) mol.L-1 obviously inhibited the protein secretion and mRNA expression of IL-6 in FLS cultured with the supernatant from U937 cell stimulated with LPS, and the inhibitory effects increased as the concentrations of indomethacin increased. CONCLUSION: Indomethacin can inhibit the increase of IL-6 expression caused by supernatant of U937 cells stimulated with LPS in FLS.

AIF-mediated mitochondrial pathway is critical for the protective effect of diazoxide against SH-SY5Y cell apoptosis.

It has been well established that the mitochondrial ATP-sensitive potassium channel (mitoK(ATP)) opener, diazoxide, has protective effects on the heart and brain following ischemia/reperfusion injury. However, the mechanism of the neuroprotective effects of diazoxide remains unclear. This study highlights the anti-apoptotic effects of the drug, which are mediated by specific regulation of apoptosis-inducing factor (AIF) in the process of oxygen and glucose deprivation (OGD)-induced apoptosis in SH-SY5Y cells. Our data showed that pretreatment with diazoxide in SH-SY5Y cells following OGD concentration-dependently increased cell viability. Compared to cells induced by OGD alone, cells pretreated with diazoxide displayed reduced rates of apoptosis, increased mitochondrial transmembrane potential (ΔΨm), and reduced AIF translocation to the cell nucleus. The protective effects of preconditioning with diazoxide were attenuated by 5-hydroxydecanoic acid (5-HD), a selective mitoK(ATP) channel antagonist. Meanwhile, cell death was blocked in OGD-induced cells stably transfected with the AIF-shRNA plasmid, and down-regulation of AIF reduced the diazoxide-mediated prevention of cell apoptosis as well as the loss of ΔΨm induced by OGD. Taken together, our results demonstrate for the first time that the AIF-mediated mitochondrial pathway plays a critical role in the protective effect of diazoxide against SH-SY5Y cell apoptosis induced by OGD. Diazoxide treatment might represent a novel therapeutic target for the treatment of ischemic cerebrovascular diseases.

Assessment of the clinical effect of Chinese medicine therapy combined with psychological intervention for treatment of patients of peri-menopausal syndrome complicated with hyperlipidemia.

OBJECTIVE: To observe the effect of Chinese medicine therapy combined with psychological intervention (combined therapy) on the clinical symptoms and levels of blood lipids and sex hormones of patients of peri-menopausal syndrome complicated with hyperlipidemia. METHODS: With the use of a randomizing digital table method, 185 patients that fit the registration standard were randomly assigned to three groups. The 59 cases in Group A were treated with two Chinese patents, Kunbao Pill and Modified Xiaoyao Pill; the 63 in Group B received psychological intervention alone; and the 63 in Group C were treated with both (the combined therapy), with the treatment course for all six months. The items of observation included: (1) scoring by SCL-90 on eight factors and seven symptoms; (2) scoring on Chinese medicine symptoms by Kupermann scale, including anxiety and bad temper, scorching sense action with sweating, dizziness, tinnitus, soreness and weakness of the loin and knees, palpitation, insomnia, lassitude, weakness, and hyposexuality; (3) blood contents of total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), apoprotein AI (ApoAI) and B (ApoB); (4) levels of sex hormones, including estradiol (E(2)), progesterone (P), pituitary prolactin (PRL), follicular stimulating hormone (FSH), and), luteinzing hormone (LH) in some randomly selected patients; (5) adverse reaction; and (6) one-year follow-up study on long-term effect. RESULTS: A total of 21 patients (6, 8, and 7 cases in Groups A, B, and C, respectively) dropped out; the drop-out rate was insignificant among groups. (1) The markedly effective rates in Group A, B, and C were 26.42% (14/53), 18.18% (10/55), and 53.57% (30/56), respectively, and the total effective rates in them were 64.15% (34/53), 50.91% (28/55), and 87.50% (49/56), respectively, suggesting the therapeutic efficacy in Group C was significantly better than that in Groups A and B (P<0.01). (2) SCL-90 scoring showed that the total scores decreased significantly after treatment in Group C (P<0.01), but remained unchanged in Groups A and B (P>0.05). (3) Scoring on Chinese medicine symptoms showed the same results as shown by SCL-90 scoring in terms of total scores and individual symptoms, except that menstrual disorder and amenorrhea were unchanged in all three groups (P>0.05). (4) Levels of HDL-C, ApoAI, and E(2) increased and those of TG, TC, LDL-C, ApoB, FSH, and LH decreased after treatment in Group C, reaching near normal levels; similar trends of blood lipids were shown in Group A, but the level of sex hormones was unchanged. In Group B all the above-mentioned indices were unchanged (P>0.05). (5) A one-year follow-up study showed the markedly effective rate and the total effective rate in Group C were higher than those in the other two groups respectively (P<0.01). (6) No adverse reaction was found. CONCLUSION: Chinese medicine therapy combined with psychological intervention could not only improve the nervous symptoms, but also regulate the blood levels of lipids and sex hormones in patients of peri-menopausal syndrome complicated with hyperlipidemia.