Wangjing Hospital of China Academy of Chinese Medical Sciences

Vascular complications of diabetes pose a severe threat to human health. Prevention and treatment protocols based on a single vascular complication are no longer suitable for the long-term management of patients with diabetes. Diabetic panvascular disease (DPD) is a clinical syndrome in which vessels of various sizes, including macrovessels and microvessels in the cardiac, cerebral, renal, ophthalmic, and peripheral systems of patients with diabetes, develop atherosclerosis as a common pathology. Pathological manifestations of DPDs usually manifest macrovascular atherosclerosis, as well as microvascular endothelial function impairment, basement membrane thickening, and microthrombosis. Cardiac, cerebral, and peripheral microangiopathy coexist with microangiopathy, while renal and retinal are predominantly microangiopathic. The following associations exist between DPDs: numerous similar molecular mechanisms, and risk-predictive relationships between diseases. Aggressive glycemic control combined with early comprehensive vascular intervention is the key to prevention and treatment. In addition to the widely recommended metformin, glucagon-like peptide-1 agonist, and sodium-glucose cotransporter-2 inhibitors, for the latest molecular mechanisms, aldose reductase inhibitors, peroxisome proliferator-activated receptor-γ agonizts, glucokinases agonizts, mitochondrial energy modulators, etc. are under active development. DPDs are proposed for patients to obtain more systematic clinical care requires a comprehensive diabetes care center focusing on panvascular diseases. This would leverage the advantages of a cross-disciplinary approach to achieve better integration of the pathogenesis and therapeutic evidence. Such a strategy would confer more clinical benefits to patients and promote the comprehensive development of DPD as a discipline.

Iron plays a crucial role in many physiological processes of the human body, but iron is continuously deposited in the brain as we age. Early studies found iron overload is directly proportional to cognitive decline in Alzheimer's disease (AD). Amyloid precursor protein (APP) and tau protein, both of which are related to the AD pathogenesis, are associated with brain iron metabolism. A variety of iron metabolism-related proteins have been found to be abnormally expressed in the brains of AD patients and mouse models, resulting in iron deposition and promoting AD progression. Amyloid β (Aβ) and hyperphosphorylated tau, two pathological hallmarks of AD, can also promote iron deposition in the brain, forming a vicious cycle of AD development-iron deposition. Iron deposition and the subsequent ferroptosis has been found to be a potential mechanism underlying neuronal loss in many neurodegenerative diseases. Iron chelators, antioxidants and hepcidin were found useful for treating AD, which represents an important direction for AD treatment research and drug development in the future. The review explored the deep connection between iron dysregulation and AD pathogenesis, discussed the potential of new hypothesis related to iron dyshomeostasis and ferroptosis, and summarized the therapeutics capable of targeting iron, with the expectation to draw more attention of iron dysregulation and corresponding drug development.

Worldwide, cancer has become one of the leading causes of mortality. Peroxisome Proliferator-Activated Receptors (PPARs) is a family of critical sensors of lipids as well as regulators of diverse metabolic pathways. They are also equipped with the capability to promote eNOS activation, regulate immunity and inflammation response. Aside from the established properties, emerging discoveries are also made in PPAR’s functions in the cancer field. All considerations are given, there exists great potential in PPAR modulators which may hold in the management of cancers. In particular, PPAR-γ, the most expressed subtype in adipose tissues with two isoforms of different tissue distribution, has been proven to be able to inhibit cell proliferation, induce cell cycle termination and apoptosis of multiple cancer cells, promote intercellular adhesion, and cripple the inflamed state of tumor microenvironment, both on transcriptional and protein level. However, despite the multi-functionalities, the safety of PPAR-γ modulators is still of clinical concern in terms of dosage, drug interactions, cancer types and stages, etc. This review aims to consolidate the functions of PPAR-γ, the current and potential applications of PPAR-γ modulators, and the challenges in applying PPAR-γ modulators to cancer treatment, in both laboratory and clinical settings. We sincerely hope to provide a comprehensive perspective on the prospect of PPAR-γ applicability in the field of cancer treatment.

Visual inspection of world maps shows that coronavirus disease 2019 (COVID-19) is less prevalent in countries closer to the equator, where heat and humidity tend to be higher. Scientists disagree how to interpret this observation because the relationship between COVID-19 and climatic conditions may be confounded by many factors. We regress the logarithm of confirmed COVID-19 cases per million inhabitants in a country against the country's distance from the equator, controlling for key confounding factors: air travel, vehicle concentration, urbanization, COVID-19 testing intensity, cell phone usage, income, old-age dependency ratio, and health expenditure. A one-degree increase in absolute latitude is associated with a 4.3% increase in cases per million inhabitants as of January 9, 2021 (p value < 0.001). Our results imply that a country, which is located 1000 km closer to the equator, could expect 33% fewer cases per million inhabitants. Since the change in Earth's angle towards the sun between equinox and solstice is about 23.5°, one could expect a difference in cases per million inhabitants of 64% between two hypothetical countries whose climates differ to a similar extent as two adjacent seasons. According to our results, countries are expected to see a decline in new COVID-19 cases during summer and a resurgence during winter. However, our results do not imply that the disease will vanish during summer or will not affect countries close to the equator. Rather, the higher temperatures and more intense UV radiation in summer are likely to support public health measures to contain SARS-CoV-2.

BACKGROUND: Hepatocellular carcinoma (HCC) is a common malignant tumor with limited treatment options. Conventional antitumor therapy combined with traditional Chinese medicine (TCM) to limit tumor progression has gradually become the focus of complementary and alternative therapies for HCC treatment. The Fuzheng Jiedu Xiaoji formulation (FZJDXJ) alleviates the clinical symptoms of patients and inhibits tumor progression, but its curative effect still requires extensive clinical research and mechanistic analysis. PURPOSE: To explore the effectiveness of FZJDXJ in HCC patients and investigate its biological function and mechanism underlying anticancer therapy. METHODS: This randomized controlled clinical trial enrolled 291 HCC patients receiving transcatheter arterial chemoembolization (TACE) therapy; patients received either FZJDXJ combined with standard treatment, or standard treatment alone, for 48 weeks. Statistical analyses were performed according to survival time at the end of the trial. The main constituents of the FZJDXJ extracts were identified and evaluated using high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) and molecular docking. The antitumor effects of FZJDXJ and its specific biological mechanism of action were studied. RESULTS: After 48 weeks of treatment, one-year overall survival (OS) and progression-free survival (PFS) were significantly different between the two groups. Co-administration of FZJDXJ and TACE prolonged the OS of HCC patients, especially in BCLC A or B stage. FZJDXJ and TACE treatment effectively extended the PFS of patients, especially in the BCLC B stage. HPLC-MS/MS identified 1619 active constituents of FZJDXJ, including formononetin, chlorogenic acid (CGA), caffeic acid, luteolin, gallic acid, diosgenin, ergosterol endoperoxide, and lupeol, which may function through the AKT/CyclinD1/p21/p27 pathways. Through molecular docking, CGA and gallic acid could effectively combine with Thr308, an important phosphorylation site of AKT1. FZJDXJ inhibited tumor growth in nude mice. In vitro, FZJDXJ-mediated serum inhibited the proliferation, migration, and invasion of liver cancer cells, and promoted cell apoptosis. CONCLUSION: Clinically, FZJDXJ combined with TACE therapy significantly prolonged OS and PFS and reduced the mortality rate of HCC patients. Mechanistically, FZJDXJ effectively inhibited the proliferation and migration of liver cancer cells through the modulation of the AKT/CyclinD1/p21/p27 pathways, and may be a promising TCM drug for anti-HCC therapy.

OBJECTIVE: The aim of the present study was to reveal the case characteristics of osteonecrosis of the femoral head (ONFH) in Mainland China. METHODS: This cross-sectional epidemiological study derived data for ONFH patients from July 2016 to December 2018 from the China Osteonecrosis of the Femoral Head Database (CONFHD). The derived data included gender, age, body mass index (BMI), height, occupation, region, and etiology of femoral head necrosis. A descriptive analysis was performed to summarize the epidemiological characteristics of the case data in the CONFHD. RESULTS: A total of 1844 ONFH patients (2945 hips) were included in this study, comprising 1302 men and 542 women. The age of patients ranged from 18 to 95 years, with a median of 50 years, and the male to female ratio was 2.4. Male patients are younger than female patients (48.26 ± 12.56 years old and 55.56 ± 14.94 years old, respectively). Among the 1844 patients (2945 hips), there were 528 (17.92%) hips at ARCO stage I, 941 (31.99%) hips at ARCO stage II, 873 (29.63%) hips at ARCO stage III, and 603 (20.46%) hips at ARCO stage IV. In the subclassification of ARCO stages I and II, the majority of cases were type C; type A comprised the majority in the subclassification of ARCO stage III. According to the Kellgren-Lawrence classification system, among the 603 ARCO stage IV hips, there were 178 (29.52%) grade 1 hips, 201 (33.34%) grade 2 hips, 176 (29.18%) grade 3 hips, and 48 (7.96%) grade 4 hips. Most were from three provinces: Henan (27.3%), Shanxi (13.9%), and Shandong (11.9%). Regarding BMI, 982 patients (53.25%) were overweight or obese. Among all patients, the largest proportion of patients engaged in level IV manual work. Of all the patients, there were 495 (26.84%) with steroid-induced ONFH, 685 (37.15%) were alcoholics, and 290 (15.73%) had traumatic ONFH. The 495 patients with steroid-induced ONFH included 278 men (56.16%) and 217 women (43.84 %), had a complete history of hormone use. Among the primary diseases, there were 195 cases (39.39%) of immune system diseases, followed by dermatological diseases, respiratory diseases, nephropathy, and other diseases. There were a total of 685 patients with alcoholic ONFH, 589 of these patients (85.99%) were men. A total of 188 (27.45%) patients had drunk alcohol for 6-10 years (comprising the highest proportion), and 280 patients (40.88%) consumed 3001-3500 mL of alcohol each week (the highest proportion). CONCLUSION: Osteonecrosis of the femoral head most commonly occurs after the age of 40. Male patients have an earlier onset than female patients, and the number of male patients is approximately twice that of female patients. The BMI of patients was mainly in the overweight and obese range, and half of these patients engaged in level IV manual work. From the imaging findings, the numbers of hips at ARCO stages II and III were greatest, and the number at stage I was relatively small. Among all the causes of disease, alcohol, steroid use and trauma were the three most common reasons for ONFH.

Synaptic dysfunction is closely related to Alzheimer’s disease (AD) which is also recognized as synaptic disorder. β-amyloid (Aβ) is one of the main pathogenic factors in AD, which disrupts synaptic plasticity and mediates the synaptic toxicity through different mechanisms. Aβ disrupts glutamate receptors, such as NMDA and AMPA receptors, which mediates calcium dyshomeostasis and damages synapse plasticity characterized by long-term potentiation (LTP) suppression and long-term depression (LTD) enhancement. As Aβ stimulates and Ca 2+ influx, microglial cells and astrocyte can be activated and release cytokines, which reduces glutamate uptake and further impair synapse function. Besides, extracellular glutamate accumulation induced by Aβ mediates synapse toxicity resulting from reduced glutamate receptors and glutamate spillovers. Aβ also mediates synaptic dysfunction by acting on various signaling pathways and molecular targets, disrupting mitochondria and energy metabolism. In addition, Aβ overdeposition aggravates the toxic damage of hyperphosphorylated tau to synapses. Synaptic dysfunction plays a critical role in cognitive impairment of AD. The review addresses the possible mechanisms by which Aβ mediates AD-related synaptic impairment from distant perspectives.

Background Gastro-oesophageal reflux disease (GORD) is one of the most common diseases presenting to gastroenterology clinics. Acupuncture is widely used as a complementary and alternative treatment for patients with GORD. Objective To explore the effectiveness of acupuncture for the treatment of GORD. Methods Four English and four Chinese databases were searched through June 2016. Randomised controlled trials investigating the effectiveness of manual acupuncture or electroacupuncture (MA/EA) for GORD versus or as an adjunct to Western medicine (WM) were selected. Data extraction and quality evaluation were performed by two authors independently and RevMan 5.2.0 was used to analyse data. Results A total of 12 trials involving 1235 patients were included. Meta-analyses demonstrated that patients receiving MA/EA combined with WM had a superior global symptom improvement compared with those receiving WM alone (relative risk (RR) 1.17, 95% CI 1.09 to 1.26; p=0.03; six studies) with no significant heterogeneity (I 2 =0%, p=0.41). Recurrence rates of those receiving MA/EA alone were lower than those receiving WM (RR 0.42,95% CI 0.29 to 0.61; p&lt;0.001; three studies) with low heterogeneity (I 2 =7%, p=0.34), while global symptom improvement (six studies) and symptom scores (three studies) were similar (both p&gt;0.05). Descriptive analyses suggested that acupuncture also improves quality of life in patients with GORD. Conclusion This meta-analysis suggests that acupuncture is an effective and safe treatment for GORD. However, due to the small sample size and poor methodological quality of the included trials, further studies are required to validate our conclusions. Trial registration number PROSPERO Systematic review registration no. CRD42016041916.

Treatment of functional dyspepsia is difficult due to various pathophysiological factors. The proposed method of transcutaneous auricular vagal nerve stimulation improves symptoms of both dyspepsia and depression/anxiety, and gastric functions (accommodation and slow waves), possibly mediated via the enhancement of vagal efferent activity. This noninvasive and easy-to-implement neuromodulation method will be well received by patients and healthcare providers.

The mobile health (mHealth) industry is an enormous global market; however, the dropout or continuance of mHealth is a major challenge that is affecting its positive outcomes. To date, the results of studies on the impact factors have been inconsistent. Consequently, research on the pooled effects of impact factors on the continuance intention of mHealth is limited. Therefore, this study aims to systematically analyze quantitative studies on the continuance intention of mHealth and explore the pooled effect of each direct and indirect impact factor. Until October 2021, eight literature databases were searched. Fifty-eight peer-reviewed studies on the impact factors and effects on continuance intention of mHealth were included. Out of the 19 direct impact factors of continuance intention, 15 are significant, with attitude (β = 0.450; 95% CI: 0.135, 0.683), satisfaction (β = 0.406; 95% CI: 0.292, 0.509), health empowerment (β = 0.359; 95% CI: 0.204, 0.497), perceived usefulness (β = 0.343; 95% CI: 0.280, 0.403), and perceived quality of health life (β = 0.315, 95% CI: 0.211, 0.412) having the largest pooled effect coefficients on continuance intention. There is high heterogeneity between the studies; thus, we conducted a subgroup analysis to explore the moderating effect of different characteristics on the impact effects. The geographic region, user type, mHealth type, user age, and publication year significantly moderate influential relationships, such as trust and continuance intention. Thus, mHealth developers should develop personalized continuous use promotion strategies based on user characteristics.

INTRODUCTION: Gastrointestinal (GI) motility disorders are common in clinical settings, including esophageal motility disorders, gastroesophageal reflux disease, functional dyspepsia, gastroparesis, chronic intestinal pseudo-obstruction, post-operative ileus, irritable bowel syndrome, diarrhea and constipation. While a number of drugs have been developed for treating GI motility disorders, few are currently available. Emerging electrical stimulation methods may provide new treatment options for these GI motility disorders. Areas covered: This review gives an overview of electrical therapies that have been, and are being developed for GI motility disorders, including gastroesophageal reflux, functional dyspepsia, gastroparesis, intestinal motility disorders and constipation. Various methods of gastrointestinal electrical stimulation are introduced. A few methods of nerve stimulation have also been described, including spinal cord stimulation and sacral nerve stimulation. Potentials of electrical therapies for obesity are also discussed. PubMed was searched using keywords and their combinations: electrical stimulation, spinal cord stimulation, sacral nerve stimulation, gastrointestinal motility and functional gastrointestinal diseases. Expert commentary: Electrical stimulation is an area of great interest and has potential for treating GI motility disorders. However, further development in technologies (devices suitable for GI stimulation) and extensive clinical research are needed to advance the field and bring electrical therapies to bedside.

Focal bone destruction within inflamed joints is the most specific hallmark of rheumatoid arthritis (RA). Our previous study indicated that the therapeutic efficiency of triptolide in RA may be due partially to its chondroprotective and anti-inflammatory effects. However, its roles in bone destruction are still unclear. In this study, our data firstly showed the therapeutic effects of triptolide on severity of arthritis and arthritis progression in collagen-induced arthritis (CIA) mice. Then, by micro-CT quantification, triptolide treatment significantly increased bone mineral density, bone volume fraction, and trabecular thickness and decreased trabecular separation of inflamed joints. Interestingly, triptolide treatment could prevent the bone destruction by reducing the number of osteoclasts in inflamed joints, reducing the expression of receptor activator of NF- κ B (RANK) ligand (RANKL) and RANK, increasing the expression of osteoprotegerin (OPG), at both mRNA and protein levels, and decreasing the ratio of RANKL to OPG in sera and inflamed joints of CIA mice, which were further confirmed in the coculture system of human fibroblast-like synovial and peripheral blood mononuclear cells. These findings offer the convincing evidence for the first time that triptolide may attenuate RA partially by preventing the bone destruction and inhibit osteoclast formation by regulating RANKL/RANK/OPG signal pathway.

Inflammatory markers have a wide range of predictive values in the prognosis of non-small lung cancer (NSCLC). Poor nutritional status usually means a poor prognosis in patients with NSCLC, which is widely recognized by oncologists and nutritionists. Serum albumin has a certain value in evaluating the prognosis of patients. Several inflammatory albumin-related markers have been proposed, but they have not been widely used in predicting the prognosis of NSCLC in clinical practice. We aim to systematically review the published clinical evidence of albumin-related inflammatory markers in predicting the prognosis of NSCLC and to describe their progress and value. The results showed that the markers included in the review could be prognostic indicators in patients with NSCLC. However, we found that the cut-off value of albumin-related inflammatory markers with quantitative nature was very chaotic and needed to be defined by recognized standards. We summarized and compared the advantages and disadvantages of these markers, but a prospective cohort study with long-term follow-up after adjustment for important confounders is still necessary. Whether the results and conclusions could be directly applied in clinical practice needs to be identified and evaluated. There is an urgent need to classify and standardize the albumin-related inflammatory markers that play an important role in the prognosis of NSCLC, which is the key to ensuring the transformation from clinical study to clinical application.

Background Osteoporosis has already been a growing health concern worldwide. The influence of living area, lifestyle, socioeconomic, and medical conditions on the occurrence of osteoporosis in the middle-aged and elderly people in China has not been fully addressed. Methods The study was a multicenter cross-sectional study on the middle-aged and elderly permanent residents, which gathered information of 22,081 residents from June 2015 to August 2021 in seven representative regions of China. The bone mineral density of lumbar vertebrae and hip were determined using the dual-energy X-ray absorptiometry densitometer instruments. Serum levels of bone metabolism markers were also measured. Information about education, smoking, and chronic diseases were also collected through face-to-face interviews. Age-standardized prevalence and 95% confidence intervals (CIs) of osteopenia and osteoporosis by various criteria were estimated by subgroups and overall based on the data of China 2010 census. The relationships between the osteoporosis or osteopenia and sociodemographic variables or other factors were examined using univariate linear models and multivariable multinomial logit analyses. Results After screening, 19,848 participants (90%) were enrolled for the final analysis. The age-standardized prevalence of osteoporosis was estimated to be 33.49%(95%CI, 32.80–34.18%) in the middle-aged and elderly Chinese permanent residents, for men and women was 20.73% (95% CI, 19.58–21.87%) and 38.05% (95% CI, 37.22–38.89%), respectively. The serum concentrations of bone metabolic markers, and calcium and phosphorus metabolism were influenced by age, body mass index (BMI), gender, education level, regions, and bone mass status. Women, aged 60 or above, BMI lower than 18.5 kg/m 2 , low education level including middle school, primary school and no formal education as well as current regular smoking, a history of fracture were all significantly associated with a higher risk of osteoporosis and osteopenia in the middle-aged and elderly people. Conclusions This study revealed dramatic regional differences in osteoporosis prevalence in China, and female, aged 60 or older, low BMI, low education level, current regular smoking, and a history of fracture were associated with a high risk of osteoporosis. More prevention and treatment resources should be invested into particular population exposed to these risk factors.

BACKGROUND: Functional dyspepsia (FD) is a common digestive disease with limited therapeutic options. According to evidence-based clinical practice, acupuncture or electroacupuncture (EA) seems to be a promising therapy for patients with FD. However, there is still a lack of systematic reviews that have analyzed current clinical trials for a better understanding of mechanisms involved in the ameliorating effect of acupuncture and EA on FD. AIM: To evaluate the results and qualities of existing clinical evidence for researching the underlying mechanisms of acupuncture/EA in treating FD. METHODS: A systematic search of the literature was performed to identify randomized controlled trials in which research on the mechanism of acupuncture or EA was conducted in FD patients. Databases searched included PubMed, EMBASE, Cochrane Library, and Web of Science. Data extraction and quality assessment were completed by two investigators independently and the results of quality evaluation were exported through Review Manager V5.3. RESULTS: Eight studies were included in this review with a total of 17 items for detecting techniques for mechanistic research. Positive effects of acupuncture and EA were observed in regulating gastric motility, gastric accommodation, mental status, gastrointestinal hormones, and central and autonomic functions while improving dyspeptic symptoms and quality of life. CONCLUSION: The key findings of this systematic review support the potential of acupuncture and EA in altering the heterogeneous pathophysiology in patients with FD. However, high-quality studies with well-planned designs are necessary to provide more credible evidence.

Steroid-induced osteonecrosis of the femoral head (steroid-induced ONFH) is characterized by increase of intraosseous pressure because of lipid metabolism disturbance such as elevation of adipogenesis and fat cell hypertrophy in the bone marrow, subsequently leading to disturbances of coagulation-fibrinolysis system in the femoral head and finally resulting in bone ischemia. Pravastatin has been demonstrated to be useful in preventing steroid-induced ONFH in animal models. However, its exact mechanisms acting on this disease have not been fully elucidated. To address this problem, steroid-induced ONFH rat model was constructed to evaluate the effects of pravastatin treatment on the osteonecrotic changes and repair processes. Then, Micro-CT-based micro-angiography was performed to assess the effects of pravastatin treatment on vascularization. In addition, serum lipid levels were detected by haematological examination. After that, the expression of peroxisome proliferator-activated receptor gamma (PPARγ), Wnt3a, low density lipoprotein receptor-related protein 5 (LRP5), β-catenin and runt-related transcription factor 2 (RUNX2) at both mRNA and protein levels were further detected by immunohistochemistry, real-time quantitative PCR, and Western blot analyses. The results, the ratio of empty lacuna, adipose tissue area, and adipocyte perimeter in the bone marrow were dramatically lower in the pravastatin treatment groups than in the model group (all P < 0.05). Moreover, by micro-CT quantification, pravastatin treatment dose-dependently increased vessel volume, vessel surface, percentage of vessel volume, and vessel thickness of the femoral heads of steroid-induced ONFH rats. Importantly, pravastatin treatment could prevent steroid-induced ONFH by suppressing the expression of PPARγ, and increasing the expression of Wnt3a, LRP5, β-catenin, and RUNX2, at both mRNA and protein levels, in the femoral heads of steroid-induced ONFH rats. In conclusion, Pravastatin may prevent steroid-induced ONFH by suppressing PPARγ expression and activating Wnt signaling pathway.

BACKGROUND: Steroid-induced osteonecrosis of the femoral head (steroid-induced ONFH) presents great challenges due to the various effects of steroids on multi-system pathways involved into osteoblast differentiation, osteoblast and osteoclast apoptosis, lipid metabolism, calcium metabolism and coagulation. As one of the most frequently used herbs in Traditional Chinese Medicine formulas that are prescribed for the regulation of bone and mineral metabolism, the therapeutic effects of Achyranthes bidentata on steroid-induced ONFH remain unclear. Thus, the aim of the current study was to verify whether Achyranthes bidentata extract (ABE) can be used to prevent steroid-induced ONFH and to investigate its underlying pharmacological mechanisms. METHODS: Steroid-induced ONFH rat models were established to evaluate the effects of ABE treatment on osteonecrotic changes and repair processes. Microfocal computed tomography (Micro-CT) was performed to assess the effects of ABE treatment on bone mass, microstructure, and vascularization. Then, the effects of ABE treatment on osteoclast differentiation and bone formation were also evaluated in vivo and in vitro. In addition, receptor activator of nuclear factor kappa B (RANK), RANK ligand (RANKL), and osteoprotegerin (OPG) expression in sera, femoral heads and bone marrow-derived mesenchymal stem cells (BMSCs) were detected at both protein and mRNA levels. RESULTS: The ratio of empty lacuna, adipose tissue area, and adipocyte perimeter in the bone marrow were markedly lower in the ABE treatment groups than in the model group. Micro-CT evaluation indicated that ABE treatment could improve the microstructure of the trabecular bone, increase bone mineral density and promote vascularization in steroid-induced ONFH rats. Moreover, ABE treatment inhibited osteoclast differentiation and activated bone formation markers. Interestingly, OPG downregulation, RANK and RANKL upregulation, and an increased ratio of RANKL to OPG in sera and necrotic femoral head could be reversed by ABE treatment, which also effectively inhibited RANKL-induced osteoclast differentiation and regulated RANKL and OPG expression of in vitro. CONCLUSION: ABE may prevent steroid-induced ONFH and alleviate steroid-induced bone deterioration by regulating the RANKL/RANK/OPG signaling pathway.

Ovarian cancer (OC) is one of the deadliest malignant tumors affecting women worldwide. The predictive value of some blood inflammatory composite markers in OC has been extensively reported. They can be used for early detection and differential diagnosis of OC and can be used for predicting survival, treatment response, and recurrence in the affected patients. Here, we reviewed the predictive values of composite inflammatory markers based on complete blood count, namely neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), monocyte-to-lymphocyte ratio, and systemic inflammation index and markers based on blood protein, namely C-reactive protein-to-albumin ratio and prognostic nutritional index in OC, with a focus on NLR and PLR. We referred to the clinical studies on these six markers, reviewed the patient population, and summarized the marker cut-off values, significance, and limitations of these studies. All these studies were retrospective and most of them were single-center clinical studies with small sample sizes. We found that the cut-off values of these markers have not been unified, and methods used to determine these values varied among studies. The predictive value of these markers on survival was mainly reflected in the postoperative patients of multiple subtypes of ovarian cancer including epithelial OC, high-grade serous ovarian carcinoma, and ovarian clear cell carcinoma. We focused on NLR and PLR and calculated their pooled hazard ratios. NLR and PLR were reliable in predicting overall and progression-free survivals in patients with OC. Therefore, it is necessary to adjust important confounding factors and conduct a long-term follow-up prospective cohort study to further clarify the cut-off values of NLR and PLR and their clinical applications.

OBJECTIVES: Duhuo Jisheng decoction (DJD) is considered beneficial for controlling knee osteoarthritis (KOA)-related symptoms in some Asian countries. This review compiles the evidence from randomised clinical trials and quantifies the effects of DJD on KOA. DESIGNS: 7 online databases were investigated up to 12 October 2015. Randomised clinical trials investigating treatment of KOA for which DJD was used either as a monotherapy or in combination with conventional therapy compared to no intervention, placebo or conventional therapy, were included. The outcomes included the evaluation of functional activities, pain and adverse effect. The risk of bias was evaluated using the Cochrane Collaboration tool. The estimated mean difference (MD) and SMD was within a 95% CI with respect to interstudy heterogeneity. RESULTS: 12 studies with 982 participants were identified. The quality presented a high risk of bias. Meta-analysis found that DJD combined with glucosamine (MD 4.20 (1.72 to 6.69); p<0.001) or DJD plus meloxicam and glucosamine (MD 3.48 (1.59 to 5.37); p<0.001) had a more significant effect in improving Western Ontario and McMaster Universities Arthritis Index (total WOMAC scores). Also, meta-analysis presented more remarkable pain improvement when DJD plus sodium hyaluronate injection (MD 0.89 (0.26 to 1.53); p=0.006) was used. These studies demonstrated that active treatment of DJD in combination should be practiced for at least 4 weeks. Information on the safety of DJD or comprehensive therapies was insufficient in few studies. CONCLUSIONS: DJD combined with Western medicine or sodium hyaluronate injection appears to have benefits for KOA. However, the effectiveness and safety of DJD is uncertain because of the limited number of trials and low methodological quality. Therefore, practitioners should be cautious when applying DJD in daily practice. Future clinical trials should be well designed; more research is needed.

Background— Tanshinone IIA (Tan IIA), a lipophilic constituent from Salvia miltiorrhiza Bunge, has shown a promising cardioprotective effect including anti-atherosclerosis. This study aims at exploring Tan IIA’s anti-inflammatory and immune-regulating roles in stabilizing vulnerable atherosclerotic plaque in ApoE deficient (ApoE-/-) mice. Methods— Male ApoE-/- mice (6 weeks) were fed with high fat diet for 13 weeks and then randomized to model group (MOD) or Tan IIA groups [high dose: 90 mg/kg/day (HT), moderate dose: 30 mg/kg/day (MT), low dose: 10 mg/kg/day (LT)] or atorvastatin group (5mg/kg/day, ATO) for 13 weeks. Male C57BL/6 mice (6 weeks) were fed with ordinary rodent chow as control. The plaque stability was evaluated according to the morphology and composition of aortic atherosclerotic (AS) plaque in H&E staining and Movat staining sections by calculating the area of extracellular lipid, collagenous fiber and foam cells to the plaque. The expression of Toll-like receptor 4 (TLR4)/ myeloid differentiation factor88 (MyD88)/ nuclear factor-kappa B (NF-κB) signal pathway in aorta fractions was determined by immunohistochemistry. Serum level of blood lipid were measured by turbidimetric inhibition immunoassay. The concentrations of tumor necrosis factor-α (TNF-α) and monocyte chemoattractant protein-1 (MCP-1) were detected by cytometric bead array. Results— Tan ⅡA stabilized aortic plaque with a striking reduction in the area of extracellular lipid (ATO: 13.15±1.2%, HT: 12.2±1.64%, MT: 13.93±1.59%, MOD: 18.84±1.46%, P<0.05) or foam cells (ATO: 16.05±1.26%, HT: 14.88±1.79%, MT: 16.61±1.47%, MOD: 22.08±1.69%, P<0.05) to the plaque, and an evident increase in content of collagenous fiber (ATO: 16.22±1.91%, HT: 17.58±1.33%, MT: 15.71±2.26%, LT:14.92±1.65%, MOD: 9.61±0.7%, P<0.05) to the plaque than that in the model group, concomitant with down-regulation of the protein expression of TLR4, MyD88 and NF-κB p65, and serum level of MCP-1, TNF-α in a dose-dependent manner. There were no differences in serum TC, LDL, HDL or TG levels between ApoE–/– mice and that treated with atorvastatin.Conclusions—These results suggest Tan IIA could stabilize vulnerable AS plaque in ApoE-/- mice and this anti-inflammatory and immune-regulating effect may been achieved via TLR4/MyD88/NF-κB signaling pathway.