[Association between hair trace element and all-cause death in elderly people in Hainan].

Objective: To explore the association between hair trace element and all-cause death in the elderly in Hainan Province. Methods: The subjects of the study were elderly people from China Hainan Centenarian Cohort Study, a total of 163 elderly were included. The association between hair trace element level and all-cause death was analyzed by using Cox proportional risk regression model. Results: After fully adjusting the covariates, the multiple Cox proportional hazards regression analyses showed that selenium (Se), manganese (Mn), strontium (Sr) concentrations in hair were significantly associated with all-cause mortality, the hazard ratio (HR) were 0.72 (95%CI: 0.54-0.98, P=0.035), 1.50 (95%CI: 1.07-2.11, P=0.020) and 0.54 (95%CI: 0.37-0.79, P=0.001), respectively. Subgroup and cross analysis showed that hair copper (Cu) were significant association with death in the people with anemia, the HR were 1.81 (95%CI: 1.13-2.88, P=0.013). And, hair Mn interacted with anemia, the HR was 0.46 (95%CI: 0.22-0.94, P=0.033). Conclusions: Se, Mn and Sr concentrations in hair were associated with the elevated risk for all-cause death in the elderly in Hainan. Se, Mn and Sr concentrations in hair can be used as a reference index for the prediction of the death risk of long-lived elderly in community, suggesting that the daily diet of elderly people are rich and diverse, in order to maintain normal and balanced trace element content in the body.

Pyridostigmine ameliorates pristane-induced arthritis symptoms in Dark Agouti rats.

OBJECTIVE: Rheumatoid arthritis (RA) is a chronic inflammatory disorder. Pyridostigmine (PYR), an acetylcholinesterase (AChE) inhibitor, has been shown to reduce inflammation and oxidative stress in several animal models for inflammation-associated conditions. The present study aimed to investigate the effects of PYR on pristane-induced (PIA) in Dark Agouti (DA) rats. METHOD: DA rats were intradermally infused with pristane to establish the PIA model, which was treated with PYR (10 mg/kg/day) for 27 days. The effects of PYR on synovial inflammation, oxidative stress, and gut microbiota were evaluated by determining arthritis scores, H&E staining, quantitative polymerase chain reaction, and biochemical assays, as well as 16S rDNA sequencing. RESULTS: Pristane induced arthritis, with swollen paws and body weight loss, increased arthritis scores, synovium hyperplasia, and bone or cartilage erosion. The expression of pro-inflammatory cytokines in synovium was higher in the PIA group than in the control group. PIA rats also displayed elevated levels of malondialdehyde, nitric oxide, superoxide dismutase, and catalase in plasma. Moreover, sequencing results showed that the richness, diversity, and composition of the gut microbiota dramatically changed in PIA rats. PYR abolished pristane-induced inflammation and oxidative stress, and corrected the gut microbiota dysbiosis. CONCLUSION: The results of this study support the protective role of PYR in PIA in DA rats, associated with the attenuation of inflammation and correction of gut microbiota dysbiosis. These findings open new perspectives for pharmacological interventions in animal models of RA.

Reveal the mechanisms of prescriptions for liver cancer' treatment based on two illustrious senior TCM physicians.

OBJECTIVE: To explore the core herbs of two illustrious senior Traditional Chinese Medicine (TCM) Physicians for the treatment of liver cancer, and to further clarify the gene targets and pathway mechanisms of liver cancer that the core prescription (CP) may regulate. METHODS: We used the patient information of two illustrious senior TCM physicians from the Affiliated Hospital of Shandong University of Traditional Chinese Medicine and the Affiliated Hospital of Capital Medical University as the database. The CP was analyzed using the community network algorithm. The pathway mechanism was analyzed using network pharmacology method. And the prognostic survival genes were identified using Single factor cox regression analysis. Integrative Pharmacology-based Research Platform of Traditional Chinese Medicine (TCMIP), Herb, Online Mendelian Inheritance in Man (OMIM), Genecards, Kyoto Encyclopedia of Genes and Genomes (KEGG), Genomic Data Commons (GDC), The Cancer Genome Atlas (TCGA), Gephi and R were used to mine CP, building a pathway network diagram. All the analyses were visualized. RESULTS: We found that the CP consistes of Huangqi (), Danshen (), Shuihonghuazi (), Baihuasheshecao (), Banzhilian (), and Ezhu (), which were attributed to the two physicians respectively. The CP played an anti-cancer role through such pathways as signal transduction, energy metabolism, immune system and other pathways, covering a total of 112 pathways and 176 herb-disease-related genes. Fourteen genes have a significant impact on the prognosis and survival of liver cancer. CONCLUSION: Based on the liver cancer cases of two illustrious senior TCM physicians, we obtained the CP through data mining. The CP may mainly exert anti-cancer effects by inhibiting inflammatory response, angiogenesis, and enhancing the body's immune response. We screened out 14 genes in the CP that may be related to the prognosis of liver cancer, and these genes may play an important regulatory role in the prognosis of liver cancer.

[An investigation of a food poisoning incident caused by Amanita fuliginea].

Mistakenly picking and eating poisonous mushrooms can cause acute poisoning. In August 2020, Qingdao Hospital of Traditional Chinese Medicine handled a poisonous mushroom poisoning incident, conducted epidemiological investigation on all poisoned patients, collected suspicious food, clinical manifestations, clinical test results and treatment conditions, and identified the mushrooms as Amanita fuliginea poisoning after morphological identification. In this incident, 6 people ate grey goose paste, of which 4 were sick with a incubation period of 6~12 h. The clinical manifestations were gastrointestinal symptoms such as nausea, vomiting and diarrhea, liver and kidney damage. After symptomatic support treatment, hemoperfusion or continuous hemofiltration treatment, the patients were cured and discharged. It is suggested to strengthen the popular science education on poisonous mushroom poisoning and improve the ability of identification and clinical treatment of poisonous mushrooms in grass-roots medical institutions.

[Progress in treatment for malignant pleural mesothelioma].

Malignant pleural mesothelioma (MPM) is a kind of invasive malignant tumor originated from pleural tissue. The incidence of MPM is not high in the population, but the prognosis is very poor. The median survival time is only about 12 months. Pemetrexed combined with platinum is the first-line chemotherapy regimen recommended by the current guidelines. The use of bevacizumab will further prolong the survival of chemotherapy. Once resistance happened, no anti-tumor treatment has been confirmed to achieve survival benefits. Therefore, there is no recommended standard second-line MPM regimen in international and domestic guidelines, including National Comprehensive Cancer Network (NCCN) guidelines. Vinorelbine, gemcitabine and other monotherapy regimens are commonly used in clinical practice, but the median progression free survival (PFS) is only about 3 months. Immune checkpoint inhibitors (ICIS) have been proved to have a significant inhibitory effect on tumor growth in a variety of malignant tumors, and their efficacy is related to the expression of programmed death-ligand 1(PD-L1). In unresectable MPM, programmed death 1 (PD-1)/PD-L1 inhibitors have been used in a series of clinical studies in the first-line, second-line and above treatment. Some of the results have been cited and recommended by international guidelines, but the overall efficacy improvement is still limited. This review summarizes the latest clinical studies and researches in the field of MPM treatment and predicts the directions and prospect of improving the therapeutic effect in the future.

[Safety and efficacy of ultrafiltration on heart failure patients with reduced ejection fraction and diuretic resistance: results from a single-center randomized controlled trial].

Objective: To investigate the safety and efficacy of ultrafiltration on diuretic sensitivity in heart failure patients with reduced ejection fraction and diuretic resistance. Methods: This was a single-center randomized controlled trial. A total of 148 heart failure patients with reduced ejection fraction admitted to the Hospital of Traditional Chinese Medicine of Xinjiang Uygur Autonomous Region from June 2010 to June 2020 were enrolled in this study, and these patients were randomly divided (ratio 1:1) into the ultrafiltration group (n=74) and the control group (n=74). All patients were treated with diuretics, cardiotonic, vasodilator and other comprehensive drugs according to relevant guidelines. After grouping, the patients in the control group were treated with standard treatment plan, while patients in the ultrafiltration group were treated with ultrafiltration on top of standard therapy. Diuretic drugs were discontinued during ultrafiltration, and intravenously furosemide (40 mg) was given immediately and 24 hours after the end of ultrafiltration. Clinical data including gender, age, complicated diseases, New York Heart Association (NYHA) function classification, etc. were collected. Effectiveness indicators include urine volume (the first 12-hour and 24-hour urine volume and the second 24-hour urine volume after using diuretic), body weight and dyspnea severity score. Safety indicators include systolic blood pressure, serum creatinine, serum Na+ concentration, blood K+ concentration and the number of deaths before and after intervention. Results: Two patients in the control group died due to worsening heart failure after randomization and were excluded in this study, 146 patients were finally analyzed (72 patients in the control group and 74 patients in the ultrafiltration group). There were 93 males, and the age was (68.3±11.2) years. There was no significant difference between patients in the ultrafiltration group and the control group in gender, age, body weight, course of disease, dyspnea severity score, NYHA function classification Ⅲ/Ⅳ, the proportion of patients with severe edema of both lower limbs, the proportion of patients with complicated diseases, and basic medication (all P>0.05). After using diuretics, the urine volume of the first 12-hour and 24-hour and the second 24-hour were significantly higher in the ultrafiltration group than in the control group (all P<0.05). Body weight decreased significantly after ultrafiltration treatment as compared with that before intervention in the ultrafiltration group (P<0.05). Compared with the control group, the dyspnea severity score was significantly improved in the ultrafiltration group (P<0.05). There was no significant difference in systolic blood pressure, serum creatinine, serum Na+ concentration, blood K+ concentration of patients between ultrafiltration group and control group before and after intervention (all P>0.05). During the clinical diagnosis and treatment, 2 male patients in the control group died, and the cause of death was aggravation of basic diseases complicated with acute heart failure and cardiogenic shock. There was no death in the ultrafiltration group, and there were no obvious clinical adverse events during and after ultrafiltration. Conclusion: Ultrafiltration therapy is safe and can improve diuretic sensitivity in heart failure patients with reduced ejection fraction and diuretic resistance.

[Textual research on Xilei Powder].

Xilei Powder is a commonly used prescription for the treatment of oral ulcers, and is originally used to treat scarlet fever. Scarlet fever is a warm-toxin disease from the perspective of the theory of warm disease. It is a warm infectious disease caused by epidemic. Xilei Powder was recorded in the Chinese Pharmacopoeia from 1953 edition to 2010 edition. As China joined Convention on International Trade in Endangered Species of Wild Fauna and Flora(CITES), Xilei Powder was removed from the Chinese Pharmacopoeia of 2015 edition due to the limitation of the use of animal drugs, such as ivory and rhinoceros horn. Xilei Powder has been widely used to treat such diseases as otolaryngology, fever, gynecological diseases, digestive diseases, and tumors. Does Xilei Powder have a unique place in clinical application? Can stable and effective alternative drugs be derived from original prescription? Due to the lack of theoretical studies on Xilei Powder, by consulting ancient books, monographs and papers, we comprehensively summarized and studied historical evolution and prescription connotation of Xilei Powder, and analyzed its drug origin and clinical application, in the hope to promote the theoretical study and clinical application.

[Preliminary results of Chinese magnetic sphincter augmentation in treating gastroesophageal reflux disease].

Objective: To examine the preliminary clinical efficacy of Chinese magnetic sphincter augmentation (MSA) in the treatment of gastroesophageal reflux disease (GERD). Methods: According to the enrollment criteria for the MSA developed by ShengJieKang Co. and Shanghai Chest Hospital (SS-MSA) clinical trial, a total of 19 GERD patients were treated with SS-MSA from August 2018 to January 2020 at Department of Thoracic Surgery, Shanghai Chest Hospital, Shanghai Jiao Tong University. The majority of registered cases were male patients with age of (32.2±7.3) years (range: 22 to 50 years), height of (170.7±6.2) cm (range: 160 to 179 cm) and weight of (65.2±10.3) kg (range: 47.5 to 90.0 kg). SS-MSA was implanted via laparoscopy. The major evaluation indexs of postoperative efficacy were the total time of acid exposure within 24 hours and the total number of reflux. Secondary efficacy indicators included: (1) evaluation of the average daily dose of proton pump inhibitor medications; (2) the score of GERD health related quality of life questionnaire (GERD-Q) before and after MSA implantation. Paired design t-test was used to evaluate the efficacy of the SS-MSA. Results: A total of 19 patients underwent SS-MSA surgery successfully. The history of the GERD were 19 (54) months (M(Q(R))). The operation time was 63 (22) minutes and the in-hospital stay was 3 (2) days. No obvious surgical complications occurred. Postoperative adverse events included 14 cases with mild to moderate dysphagia exited after surgery, gradually eased within 1 to 3 months, 1 case with the removal of the device after 1 month of severe swallowing difficulties, 1 case of diarrhea. No corrosion, perforation, displacement occurred. The GERD-Q score (11.0(4.5) vs. 6(1.0), t=4.274, P=0.013), 24-hour acid exposure time (6.2(4.8)% vs. 0.1(0.9)%, t=5.814, P=0.004), and Demeester score (23.72(16.20) vs. 0.96(3.10), t=6.678, P=0.003) were significantly decreased 1 year after surgery(n=5). Proton pump inhibitor reuse rates were 6/18, 5/15, 3/10, and 1/5 in 1, 3, 6 and 12 months after the operation, respectively. Conclusions: SS-MSA implantation is feasible and safe with short hospital stay and rare perioperative complications. The preliminary results is good after 1 year follow-up. It could be expected to be an ideal substitutive for future GERD treatment.

[Standardized treatment of chronic radiation-induced bowel injury].

Radiation-induced bowel injury is a common complication of radiation therapy for pelvic malignancy. Given the huge number of patients diagnosed with pelvic malignancy, the number of patients diagnosed with radiation-induced bowel injury increased year by year, which put a great burden on the clinical diagnosis and treatment of radiation-induced bowel injury. In particular, chronic radiation-induced bowel injury, which is manifested in the process of prolonged, repeated and progressive aggravation, seriously affects the physical and mental health of patients and makes clinical diagnosis and treatment difficult. However, due to insufficient attention and understanding from doctors and patients, standardized diagnosis and treatment of radiation-induced bowel injury still have a long way to go. Radiation-induced bowel injury is self-limited but irreversible. During diagnosis, we should pay attention to overall evaluation of the stage of disease based on clinical symptoms, endoscopic examination, imaging examination, pathology and nutritional risk. The treatment methods include health education, drug therapy, enema therapy, formalin local treatment, endoscopic treatment and surgical treatment, etc. The treatment decision-making should be based on clinical symptoms, endoscopic or imaging findings to alleviate the clinical symptoms of patients as the primary goal and to improve the long-term quality of life of patients as the ultimate goal.

Melatonin regulates mitochondrial function and biogenesis during rat dental papilla cell differentiation.

OBJECTIVE: The aim of this study was to investigate the effect of melatonin on mitochondria of dental papilla cells (DPCs) during the odontogenic differentiation process. MATERIALS AND METHODS: Primary DPCs were obtained from the first molar dental papilla of neonatal rats and cultured in osteogenic (OS) or basal medium supplemented with melatonin at different concentrations (0, 1 pM, 0.1 nM, 10 nM, and 1 µM) for differentiation in vitro. Effects of melatonin on differentiation, mitochondrial respiratory function, and mitochondrial biogenesis of DPCs were analyzed. RESULTS: Upon odontogenic induction, Alkaline phosphatase (ALP) activity, dentin sialophosphoprotein (DSPP), and dentin matrix protein (DMP1) expression were significantly enhanced, with a peaked expression at 10 nM of melatonin treatment. During DPCs differentiation, 10 nM melatonin could significantly induce the increase of intracellular Adenosine triphosphate (ATP), the decrease of the oxidized form of nicotinamide adenine dinucleotide (NAD+)/NADH ratio and reactive oxygen species (ROS). The mRNA and protein levels of peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α), nuclear respiratory factor 1 (NRF-1), and mitochondrial transcription factor A (TFAM) were significantly increased, and the peak level of expression was found in cells treated with 10 nM of melatonin. Furthermore, the mitochondria DNA (mtDNA) copy number was significantly decreased during DPCs differentiation. CONCLUSIONS: These findings suggest that melatonin can promote the differentiation of rat DPCs and regulate mitochondrial energy metabolism, ROS scavenging, and mitochondrial biogenesis.

Sex, Residence and Fish Intake Predict Vitamin D Status in Chinese Centenarians.

OBJECTIVES: This study aims to investigate the prevalence of vitamin D deficiency in Chinese centenarians and to identify the factors associated with vitamin D deficiency. DESIGN: Cross-sectional population-based study. SETTING: Hainan province in the south of China. PARTICIPANTS: 943 subjects aged 100 years old and older. METHODS: Details on sociodemographics and lifestyle characteristics were collected using a structured questionnaire. Anthropometrics and blood samples were obtained. Vitamin D deficiency was defined as serum 25-hydroxyvitamin D concentration < 20ng/mL (50nmol/L). RESULTS: The overall prevalence of vitamin D deficiency among these 943 centenarians was 39.9% (376 subjects) and the mean serum vitamin D concentrations were 22.7±9.5 (ng/mL). Female centenarians had higher prevalence of vitamin D deficiency than male (44.0% vs. 21.7%, P <0.001). Multivariate logistic regression analyses showed that being female, urban residency, lower body mass index, higher serum parathyroid hormone levels, no fish consumption, and less sun exposure time were all significant and independent determinants of vitamin D deficiency. No significant associations of vitamin D deficiency with ethnic, education, geographic location, tea drinking, alcohol use, or smoking were found in this study. CONCLUSION: Vitamin D deficiency was common in Chinese centenarians, especially in women. Given that vitamin D deficiency is linked to numerous adverse health outcomes, dietary, outdoor activities and other intervention measures are needed to correct vitamin D deficiency in this population.

Blocking of YY1 reduce neutrophil infiltration by inhibiting IL-8 production via the PI3K-Akt-mTOR signaling pathway in rheumatoid arthritis.

Our previous study revealed that Yin Yang 1(YY1) played an important part in promoting interleukin (IL)-6 production in rheumatoid arthritis (RA). However, whether YY1 has any role in regulation of IL-8 in RA remains unclear. YY1 and IL-8 expression in RA patients were analyzed by real-time polymerase chain reaction (PCR). Ingenuity pathway analysis (IPA) was used to analyze the signaling pathway involved in YY1-induced IL-8 production. The expression of YY1 and proteins involved in the pathway were detected by Western blot and enzyme-linked immunosorbent assay (ELISA). Migration of neutrophils was performed by chemotaxis assay. In this study, we found that high expression of IL-8 was positively associated with YY1 expression in RA. Blocking YY1 expression by YY1-short hairpin (sh)RNA lentivirus reduced IL-8 production. Mechanistically, we showed YY1 activated IL-8 production via the phosphatidylinositol-3-kinase/Akt/mammalian target of rapamycin (PI3K/Akt/mTOR) signaling pathway. Further, using a co-culture system consisting of peripheral blood mononuclear cells (PBMC) and neutrophils, we found that migration of neutrophils would be inhibited by YY1 RNA interference. Finally, using the collagen-induced arthritis animal model, we showed that treatment with the YY1-shRNA lentivirus led to reduction of IL-8 levels and attenuation of inflammation and neutrophil infiltration in vivo. Our results reveal a role of YY1 involved in neutrophil infiltration in RA via the PI3K/Akt/mTOR/IL-8 signaling pathway. YY1 may be a new therapeutic target for treatment of RA.

[Influencing factors for reproductive health of female workers in petrochemical industry].

Objective: To investigate the reproductive health status of female workers in petrochemical industry, and to provide a reference for improving reproductive health status and developing preventive and control measures for female workers in petrochemical industry. Methods: A face-to-face questionnaire survey was performed from January to October, 2016. The Questionnaire on Women's Reproductive Health was used to investigate the reproductive health of female workers in petrochemical industry. The multivariate logistic regression model was used to identify the influencing factors for reproductive health of female workers in petrochemical industry. Results: Among the 7485 female workers, 1 268 (40.9%) had abnormal menstrual period, 1 437 (46.4%) had abnormal menstrual volume, 177 (28.5%) had hyperplasia of mammary glands, and 1 807 (24.6%) had gynecological inflammation. The reproductive system diseases in female workers in petrochemical industry were associated with the factors including age, marital status, education level, unhealthy living habits, abortion, overtime work, work shift, workload, video operation, occupational exposure, positive events, and negative events, and among these factors, negative events (odds ratio[OR]= 1.856) , unhealthy living habits (OR=1.542) , and positive events (OR=1.516) had greater impact on reproductive system diseases. Conclusion: Many chemical substances in the occupational environment of petrochemical industry can cause damage to the reproductive system, which not only affects the health of the female workers, but also poses potential threats to the health of their offspring. Occupational exposure, unhealthy living habits, overtime work, and work shift have great influence on reproductive system diseases in female workers.

Leaf defense system of Robinia pseudoacacia L. seedlings exposed to 3years of elevated atmospheric CO2 and Cd-contaminated soils.

Short-term exposure to elevated CO2 increases cadmium (Cd) uptake in some plant species (wheat, poplars, and willows), which triggers an increase in antioxidative system activity to deal with additional reactive oxygen species that are generated. Here, we examined leaf defenses in Robinia pseudoacacia L. seedlings exposed to elevated CO2+Cd for 3years. Three years of elevated CO2 decreased Cd uptake into leaves and the Cd content in soils and increased the pH of rhizosphere soil relative to ambient CO2. In plants exposed to Cd stress, leaf chlorophyll content was greater under elevated CO2 than under ambient CO2. Superoxide dismutase, peroxidase, and catalase activity increased, glutathione content increased, and malondialdehyde and phytochelatins contents decreased under elevated CO2+Cd relative to Cd alone. Proline, soluble sugars, flavonoids, saponins, and phenolic acids contents were greater under elevated CO2+Cd than under Cd alone, and condensed tannin content was lower. Overall, long-term elevation of CO2 enhanced the leaf defense system of R. pseudoacacia exposed to Cd by stimulating antioxidant enzyme activity, osmotic adjustment, and the production of glutathione, flavonoids and phenolic acids. Future research should focus on understanding the mechanisms involved in the decrease in Cd uptake into leaves and Cd content in soils and the increase in rhizosphere soil pH under long-term exposure to elevated CO2.

Reduced prostate cancer risk with green tea and epigallocatechin 3-gallate intake among Hong Kong Chinese men.

BACKGROUND: In vitro and in vivo studies suggested that polyphenol epigallocatechin 3-gallate (EGCG) in tea may have anti-carcinogenic effect on prostate cells, but this protective effect has less been examined in epidemiology studies. We aimed to investigate the association between prostate cancer (PCA) risk and habitual green tea intake among Chinese men in Hong Kong; meanwhile, the relationship with EGCG was also explored. METHODS: We consecutively recruited 404 PCA cases and 395 controls from the same hospital who had complete data on habitual tea consumption, including green, oolong, black and pu'er tea. We reconstructed the level of EGCG intake according to a standard questionnaire and the analytic values for EGCG extracted from the literature published by Lin et al. in 2003. We calculated odds ratios (ORs) for tea consumption and EGCG intake using unconditional multiple logistic regression, and examined their exposure--response relationships with PCA risk. RESULTS: A total of 32 cases and 50 controls reported habitual green tea drinking, showing an adjusted OR of 0.60 (95% confidence interval (CI): 0.37, 0.98). A moderate excess risk was observed among the habitual pu'er tea drinkers (OR=1.44, 95% CI: 1.02, 1.91). A significantly lower intake of EGCG was observed among cases (54.4 mg) than the controls (72.5 mg), which resulted in an inverse gradient of PCA risk with the increasing intake of EGCG (test for trend, P=0.015). CONCLUSION: PCA risk among Chinese men in Hong Kong was inversely associated with green tea consumption and EGCG intake, but these results need to be replicated in larger studies.

Meta-analysis of traditional herbal medicine in the treatment of nonalcoholic fatty liver disease.

Traditional Chinese herbal medicine (TCM) has been found effective for nonalcoholic fatty liver disease (NAFLD) based on its unique theory system and substantial herb remedies. The aim of this meta-analysis was to evaluate the efficiency and safety of one of the TCM, Danshen in the treatment of NAFLD. Seven English and Chinese databases were searched from inceptions to December 2015. RCTs which compared Danshen with placebo in adult patients with NAFLD were included. Totally, 8 RCTs with a total of 800 patients were identified. The results showed that compared with placebo, Danshen had increased total effectiveness rate, lower level of ALT, AST, TC and TG, LDL and higher level of liver/spleen computed tomography ratio. The present meta-analysis suggests that Danshen may have positive effects on nonalcoholic fatty liver disease. Future multicenter large-sample randomized clinical trials are still needed to confirm the efficacy and safety of our study.

IL-4 administration exerts preventive effects via suppression of underlying inflammation and TNF-α-induced apoptosis in steroid-induced osteonecrosis.

UNLABELLED: Macrophages play an important role during the development of steroid-induced osteonecrosis. Interleukin (IL)-4 administration helped reduce the infiltration of M1 phenotypic macrophages and maintain the activation of M2 phenotypic macrophages, resulting in restriction of inflammation and decrease in osteocyte apoptosis. The results indicated the therapeutic potential of IL-4 in prevention of steroid-induced osteonecrosis. INTRODUCTION: Steroid-induced osteonecrosis (ON) is a debilitating disease characterized by the activation and infiltration of macrophages into the necrotic site. This study aimed to investigate the effects of IL-4 administration on macrophage polarization and the involved signaling pathways. METHODS: Fifty-six BALB/c mice were randomly divided into two groups, group M (model group) and group MI (treatment group), each containing 28 mice. ON model was induced by the injection of methylprednisolone (MPS). The mice in group MI received intra-abdominal injections of 2 µg/100 g/day of rIL-4 for five consecutive days, following the administration of MPS. Osteonecrosis was verified by histopathological staining. The expression of tumor necrosis factor-alpha (TNF-α) was analyzed by ELISA and immunohistochemistry. The infiltration of M1/M2 macrophages was examined by the expression of specific makers of F4/80, CD11c, and CD206 protein. Cell apoptosis was detected by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay, and the apoptotic signal molecules such as STAT1 and caspase-3 were examined. RESULTS: Histopathological observations indicated that IL-4 administration reduced the incidence of ON and the accumulation of osteoclasts. IL-4 administration inhibited the expression of TNF-α and reduced the infiltration of M1 phenotypic macrophages and maintained relatively high level of M2 phenotypic macrophages. Additionally, TUNEL assay suggested that IL-4 intervention could reduce the number of apoptotic cells in the necrotic zone. The anti-apoptotic mechanisms were related to STAT1 phosphorylation and the activation of caspase-3. CONCLUSIONS: Il-4 administration could alleviate steroid associated ON in mice by inhibiting the inflammatory response, the infiltration of M1 phenotypic macrophages, and suppressing TNF-a-induced osteocytic apoptosis by inhibiting the STAT1-caspase-3 signal pathway.

[A preliminary evaluation and discussion on the significance of the medical bamboo slips Ci shu (Needling Methods) unearthed from a Han tomb in the Mount. Laoguan, Chengdu].

The compilation of medical bamboo slips, Ci shu(Needling Methods), which was unearthed from a Han tomb in Mt. Laoguan, is a monograph dealing exclusively with the principles of clinical acupuncture manipulations with 40 acupuncture prescriptions, being the earliest unearthed work with documented standard methods of acupuncture manipulations and acupuncture prescriptions in China. The chapter Zhen fang (Acupuncture Prescriptions) is the earliest summary of standardized acupoint prescriptions up to now in China, which is of great significance to clinical practice directly derived from ancient clinical performance of acupuncture. The chapter Zhen fang of the book Ci shu is also one of the earliest ancient clinical reports archiving the acupoint. This may provide invaluable perspectives to the study of the conceptualization, origination, development, formation of theoretical system, and clinical application of acupoints.

Scutellaria barbata D. Don polysaccharides inhibit the growth of Calu-3 xenograft tumors via suppression of the HER2 pathway and angiogenesis.

Scutellaria barbata D. Don, a perennial herb belonging to the family Lamiaceae, is widely distributed throughout China and the Republic of Korea, and has been traditionally used in folk medicine as an antitumor and anti-inflammatory agent. Polysaccharides isolated from Scutellaria barbata D. Don (PSB), have been reported to possess antitumor effects. However, the detailed antitumor mechanisms behind the effects of PSB remain unclear. In the present study, a non-small cell lung cancer cell line harboring the HER2 gene mutation Calu-3, the Calu-3 cell line, was used to investigate the underlying mechanisms of the antitumor effects of PSB. The results revealed that PSB potently inhibited cell proliferation and human epidermal growth factor receptor (HER)2 phosphorylation in vitro, and also downregulated the expression of the downstream signaling molecules, including phosphorylated (phospho-)Akt and phospho-extracellular signal-related kinase. In vivo, PSB demonstrated efficacy at well-tolerated doses, including significant antitumor activity in a Calu-3 subcutaneous xenograft model. Immunohistochemistry (IHC) analysis revealed a PSB dose-dependent reduction of microvessel density, demonstrated by cluster of differentiation 31 staining. The present findings suggest that inhibition of tumor angiogenesis via suppression of the HER2 pathway may be one of the mechanisms by which PSB can be effective in the treatment of cancers.