Strong Metal-Support Interaction Modulation between Pt Nanoclusters and Mn3O4 Nanosheets through Oxygen Vacancy Control to Achieve High Activities for Acidic Hydrogen Evolution.

The optimization of metal-support interactions is used to fabricate noble metal-based nanoclusters with high activity for hydrogen evolution reaction (HER) in acid media. Specifically, the oxygen-defective Mn3O4 nanosheets supported Pt nanoclusters of ≈1.71 nm in diameter (Pt/V·-Mn3O4 NSs) are synthesized through the controlled solvothermal reaction. The Pt/V·-Mn3O4 NSs show a superior activity and excellent stability for the HER in the acidic media. They only require an overpotential of 19 mV to drive -10 mA cm-2 and show negligible activity loss at -10 and -250 mA cm-2 for >200 and >60 h, respectively. Their Pt mass activity is 12.4 times higher than that of the Pt/C and even higher than those of many single-atom based Pt catalysts. DFT calculations show that their high HER activity arises mainly from the strong metal-support interaction between Pt and Mn3O4. It can facilitate the charge transfer from Mn3O4 to Pt, optimizing the H adsorption on the catalyst surface and promoting the evolution of H2 through the Volmer-Tafel mechanism. The oxygen vacancies in the V·-Mn3O4 NSs are found to be inconducive to the high activity of the Pt/V·-Mn3O4 NSs, highlighting the great importance to reduce the vacancy levels in V·-Mn3O4 NSs.

Application of TCM Rehabilitation in Joint Function Recovery After Treatment of Distal Radius Fractures: A Meta-Analysis.

Objective: To evaluate the effect of traditional Chinese medicine (TCM) rehabilitation on the postoperative function of patients with distal radius fractures by Meta-analysis. Methods: PubMed, Embase, CNKI, Wanfang, and other databases were searched for retrospective controlled trials and prospective randomized controlled trials on the effect of traditional Chinese medicine rehabilitation on the function of patients with distal radius fractures after surgery from the establishment of the database to May 2023. Revman version 5.3 software was used to analyze the extracted and screened index data. Results: Eight studies involving 455 patients were included. Meta-analysis results showed Overall analysis showed that there was a significant difference in wrist function between the TCM rehabilitation group and the control group (MD = -12.16, 95%CI:-17.21 to -7.11, P < .00001), low heterogeneity (I2=40%, P = .17), the difference in dorsiflexion function between the TCM rehabilitation group and the control group was statistically significant (MD = -1.16, 95%CI:-2.24 to -0.08, P = .04), with high heterogeneity (I2=79%, P = .003), that there was a significant difference in grip strength between the TCM rehabilitation group and the control group at 6 weeks (MD= 0.48, 95%CI: 0.24 to 0.71, P < .0001) with low heterogeneity (I2=45%, P = .12), there was no significant difference between the TCM rehabilitation group and the control group (OR= -0.00, 95%CI: -0.08 to 0.08, P = .99), and there was no heterogeneity (I2=0%, P = .66). Conclusion: Traditional Chinese medicine rehabilitation treatment of distal radius fractures can increase the range of motion of wrist joints, reduce pain, shorten the rehabilitation time of patients, improve the quality of life, and is conducive to the standardized treatment of patients.

[Transcriptome data mining combined with clinical and animal experiments for identification of syndrome element marker genes during entire course of steroid-induced osteonecrosis of femoral head].

A research strategy combining transcriptome data mining and experimental verification was adopted to identify the marker genes characterizing the syndrome elements of phlegm, stasis, and deficiency in steroid-induced osteonecrosis of the femoral head(SONFH). Firstly, the common differentially expressed gene sets of SONFH with the syndromes of phlegm-stasis obstructing collaterals, vessel obstruction, and liver-kidney deficiency were obtained from the clinical transcriptomic analysis of a previous study. The differential expression trend analysis and functional gene mining were then employed to predict the candidate marker gene sets representing phlegm, stasis, and deficiency. The whole blood samples from SONFH patients, whole blood samples from SONFH rats, and affected femoral head tissue samples were collected for qPCR, which aimed to determine the expression levels of the candidate marker genes mentioned above. Furthermore, the receiver operating characteristic curve(ROC) was established to objectively evaluate the syndrome differentiation effectiveness of the candidate marker genes mentioned above. The transcriptome data analysis results showed that the candidate marker genes for phlegm was ELOVL fatty acid elongase 6(ELOVL6), and those for stasis were ankyrin 1(ANK1), glycophorin A/B(GYPA/B), and Rh-associated glycoprotein(RHAG). The candidate marker genes for deficiency were solute carrier family 2 member 1(SLC2A1) and stomatin(STOM). The qPCR results showed that compared with that in the non-SONFH group, ELOVL6 had the lowest expression level in the peripheral blood of the SONFH patients with the syndrome of phlegm-stasis obstructing collaterals(P<0.05). Compared with that in the normal control group, ELOVL6 had the lowest expression level in the peripheral blood and affected femoral head tissue of SONFH rats modeled for 4 weeks(P<0.01), and it showed better syndrome differentiation effectiveness of rats modeled for 4 weeks(AUC=0.850, P=0.006) than at other modeling time points(8, 12, 16, and 21 weeks, AUC of 0.689, 0.766, 0.588, and 0.662, respectively). Compared with that in the non-SONFH group, the expression levels of ANK1, GYPA, and RHAG were the lowest in the peripheral blood of SONFH patients with the vessel obstruction syndrome(P<0.05). The expression levels of the three genes were the lowest in the peripheral blood and affected femoral head tissue of SONFH rats modeled for 12 weeks(P<0.05, P<0.01), and their syndrome differentiation effectiveness in the rats modeled for 12 weeks(GYPA: AUC=0.861, P=0.012; ANK1: AUC=0.855, P=0.006; RHAG: AUC=0.854, P=0.009) was superior to that for 4, 8, 16, and 21 weeks(GYPA: AUC=0.646, 0.573, 0.691, and 0.617, respectively; ANK: AUC1=0.630, 0.658, 0.657, and 0.585, respectively; RHAG: AUC=0.592, 0.511, 0.515, and 0.536, respectively). Compared with the non-SONFH group, both SLC2A1 and STOM had the lowest expression levels in the peripheral blood of patients with the syndrome of liver and kidney deficiency(P<0.05). Compared with the normal control group, their expression levels were the lowest in the peripheral blood and affected femoral head tissue of SONFH rats modeled for 21 weeks(P<0.05, except STOM in the peripheral blood of rats). Moreover, the syndrome differentiation effectiveness of SLC2A1 in the rats modeled for 21 weeks(AUC=0.806, P=0.009) was superior to that for 4, 8, 12, and 16 weeks(AUC=0.520, 0.580, 0.741, 0.774, respectively), and STOM was meaningless in syndrome differentiation. In summary, the candidate marker gene for phlegm in SONFH is ELOVL6; the candidate marker genes for stasis are GYPA, RHAG, and ANK1; the candidate marker gene for deficiency is SLC2A1. The results help to reveal the biological connotations of phlegm, stasis, and deficiency in SONFH at the genetic level.

Plasma-Induced Formation of Pt Nanoparticles with Optimized Surface Oxidation States for Methanol Oxidation and Oxygen Reduction Reactions to Achieve High-Performance DMFCs.

Plasma treatment and reduction are used to synthesize Pt nanoparticles (NPs) on nitrogen-doped carbon nanotubes (p-Pt/p-NCNT) with a low Pt content. In particular, the plasma treatment is used to treat the NCNT to give it with more surface defects, facilitating a better growth of the Pt NPs, while the plasma reduction produces the Pt NPs with a reduced fraction of the surface atoms at the high oxidation states, increasing the catalytic activities of the p-Pt@p-NCNT. Even at the low Pt content (7.8 wt.%), the p-Pt@p-NCNT shows superior catalytic activities and good stabilities for methanol oxidation reaction (MOR) and oxygen reduction reaction (ORR). The density functional theory (DFT) calculations indicate that the defects generated in the plasma treatment can help the growth of the Pt NPs on the NCNTs, leading to the stronger electronic coupling between Pt and NCNT and the increased stability of the catalyst. The plasma reduction can give the Pt NPs with optimized surface oxidation states, decreasing the energy barriers of the rate-determining steps for MOR and ORR. When used as the anode and cathode catalysts for the direct methanol fuel cells (DMFCs), the p-Pt@p-NCNT exhibits a higher maximum power density of 81.9 mW cm-2  at 80 °C and shows good durability.

Topical Chinese patent medicines for chronic musculoskeletal pain: systematic review and trial sequential analysis.

PURPOSE: Chronic musculoskeletal pain (CMP) is defined as persistent or recurrent pain that occurs in the joints, musculo-soft tissue, spine or bones for more than three months and is not completely curable. Although topical Chinese patent medicine (CPM) is the most extensively utilized medication in Asia and is widely used for pain management, its efficacy remains controversial. This article presents a systematic review of clinical studies on the therapeutic properties of topical CPM for CMP patients to better inform clinical decision-making and provide additional and safer treatment options for patients with CMP. METHOD: We performed a comprehensive search on PubMed, Cochrane Library, web of science and Chinese databases (CNKI and WanFang data) from 2010 to 2022. In all the studies, knee osteoarthritis, cervical spondylosis, low back pain, and periarthritis of shoulder met the International Pain Association definition of chronic musculoskeletal pain. We included only randomized controlled trials (RCTs) using topical CPM primarily for chronic musculoskeletal pain in adults. To determine the effect of topical CPM on clinical symptoms, we extracted the Visual Analog Scale (VAS, range 0-10) and the Western Ontario and McMaster Universities Arthritis Index pain scores (WOMAC pain, range 0-20), in which the lower the score, the better the results. We also accepted the comprehensive outcome criteria developed by the Chinese National Institute of Rheumatology as an endpoint (total effectiveness rate, range 0-100%, higher score = better outcome), which assesses the overall pain, physical function and wellness. Finally, trial sequential analysis of VAS pain score and total effectiveness rate was performed using TSA software. RESULTS: Twenty-six randomized controlled trials (n = 3180 participants) compared topical CPM with oral Nonsteroidal Anti-inflammatory Drugs (NSAIDs) (n = 15), topical NSAIDs (n = 9), physiotherapy (n = 5), exercise therapy (n = 4), and intra-articular Sodium hyaluronate injection (n = 2). Sixteen studies found that topical CPM was statistically significant in improving CMP pain (measured by VAS pain and Womac pain scores)(p < 0.05), and 12 studies found topical CPMs to be more clinically effective (assessed by ≥ 30% reduction in symptom severity) in treating patients with CMP (p < 0.05). Trial sequential analysis indicates that the current available evidence is robust, and further studies cannot reverse this result. In most of the studies, randomisation, allocation concealment and blinding were not sufficiently described, and no placebo-controlled trials were identified. CONCLUSION: Most studies showed superior analgesic effects of topical CPM over various control treatments, suggesting that topical CPM may be effective for CMP and is an additional, safe and reasonable treatment option. These reported benefits should be validated in higher-quality RCTs.

[Characteristic changes of blood stasis syndrome in rat model of steroid-induced femoral head necrosis based on the combination of disease, syndrome, and symptom].

The approach combining disease, syndrome, and symptom was employed to investigate the characteristic changes of blood stasis syndrome in a rat model of steroid-induced osteonecrosis of the femoral head(SONFH) during disease onset and progression. Seventy-two male SD rats were randomized into a healthy control group and a model group. The rat model of SONFH was established by injection of lipopolysaccharide(LPS) in the tail vein at a dose of 20 µg·kg~(-1)·d~(-1) on days 1 and 2 and gluteal intramuscular injection of methylprednisolone sodium succinate(MPS) at a dose of 40 mg·kg~(-1)·d~(-1) on days 3-5, while the healthy control group received an equal volume of saline. The mechanical pain test, tongue color RGB technique, gait detection, open field test, and inclined plane test were employed to assess hip pain, tongue color, limping, joint activity, and lower limb strength, respectively, at different time points within 21 weeks of modeling. At weeks 2, 4, 8, 12, 16, and 21 after modeling, histopathological changes of the femoral head were observed by hematoxylin-eosin(HE) staining and micro-CT scanning; four coagulation items were measured by rotational thromboelastometry; and enzyme-linked immunosorbent assay(ELISA) was employed to determine the levels of six blood lipids, vascular endothelial growth factor(VEGF), endothelin-1(ET-1), nitric oxide(NO), tissue-type plasminogen activator(t-PA), plasminogen activator inhibitor factor-1(PAI-1), bone gla protein(BGP), alkaline phosphatase(ALP), receptor activator of nuclear factor-κB(RANKL), osteoprotegerin(OPG), and tartrate-resistant acid phosphatase 5b(TRAP5b) in the serum, as well as the levels of 6-keto-prostaglandin 1α(6-keto-PGF1α) and thromboxane B2(TXB2) in the plasma. The results demonstrated that the pathological alterations in the SONFH rats were severer over time. The bone trabecular area ratio, adipocyte number, empty lacuna rate, bone mineral density(BMD), bone volume/tissue volume(BV/TV), trabecular thickness(Tb.Th), trabecular number(Tb.N), bone surface area/bone volume(BS/BV), and trabecular separation(Tb.Sp) all significantly increased or decreased over the modeling time after week 4. Compared with the healthy control group, the mechanical pain threshold, gait swing speed, stride, standing time, and walking cycle of SONFH rats changed significantly within 21 weeks after modeling, with the greatest difference observed 12 weeks after modeling. The time spent in the central zone, rearing score, and maximum tilt angle in the open field test of SONFH rats also changed significantly over the modeling time. Compared with the healthy control group, the R, G, and B values of the tongue color of the model rats decreased significantly, with the greatest difference observed 11 weeks after modeling. The levels of total cholesterol(TC), total triglycerides(TG), low-density lipoprotein-cholesterol(LDL-C), and apoprotein B(ApoB) in the SONFH rats changed significantly 4 and 8 weeks after modeling. The levels of VEGF, ET-1, NO, t-PA, PAI-1, 6-keto-PGF1α, TXB2, four coagulation items, and TXB2/6-keto-PGF1α ratio in the serum of SONFH rats changed significantly 4-16 weeks after modeling, with the greatest differences observed 12 weeks after modeling. The levels of BGP, TRAP5b, RANKL, OPG, and RANKL/OPG ratio in the serum of SONFH rats changed significantly 8-21 weeks after modeling. During the entire onset and progression of SONFH in rats, the blood stasis syndrome characteristics such as hyperalgesia, tongue color darkening, gait abnormalities, platelet, vascular, and coagulation dysfunctions were observed, which gradually worsened and then gradually alleviated in the disease course(2-21 weeks), with the most notable differences occurred around 12 weeks after modeling.

[Effect of Jianpi Huogu Formula on function damage of vascular endothelial cells induced by glucocorticoid].

This study aimed to observe the intervention effect of Jianpi Huogu Formula(JPHGF) on the functional damage of vascular endothelial cells caused by glucocorticoid, and explore its action mechanism from the PI3 K/Akt and mitogen activated protein kinase(MAPK) signaling pathways. The extracted thoracic aorta ring of normal SD rats were intervened first with vascularendothelial growth factor(VEGF, 20 µg·L-1) and/or sodium succinate(MPS, 0. 04 g·L-1) in vitro and then with JPHGF(8, 16, and 32 µg·L-1) for five mcontinuous ethylpdays, rednisolofollowed nebythe statistics of the number, length, and area of microvessels budding fromvascular rings. In addition, the human umbilical vein endothelial cells(HUVECs) induced by VEGF(20 µg·L-1) were added with MPS(0. 04 g·L-1) and then with JPHGF(8, 16, and 32 µg·L-1) for observing the migration, invasion, and luminal formation abilities of HUVECs in the migration, invasion and luminal formation experiments. The protein expression levels of PI3 K, p-Akt, p-JN K, and p-ERK in HUVECs were assayed by Western blot. The results showed that JPHGF dose-dependently improved the num-ber,length, and area of microvessels in MPS-induced rat thoracic aortic ring, reversed the migration, invasion and lumen formation abiliti es of HUVECs reduced by MPS, and up-regulated the protein expression levels of PI3 K, p-Akt, and p-JNK in HUVECs. All thesehave suggested that JPHGF exerts the protective effect against hormone-induced damage to the angiogenesis of vascular endothelial cells by activating the PI3 K/Akt and MAPK signaling pathways, which has provided reference for exploring the mechanism of JPHGF in treating s teroid-induced avascular necrosis of femoral head(SANFH) and also the experimental evidence for enriching the scientific connotationof spleen-invigorating and blood-activating therapy.

[Expert consensus on clinical application of Wangbi Tablets in treating rheumatoid arthritis and knee osteoarthritis].

Wangbi Tablets are widely used in the treatment of rheumatoid arthritis, knee osteoarthritis and other diseases at pre-sent. Long-term clinical application and research have shown that this drug has a good effect in reducing the pain of related diseases and improving symptoms. Due to the lack of guidance in the instructions and currently no relevant norms to guide the clinical application of Wangbi Tablets, in order to further improve clinicians' understanding of the drug and fully tap the clinical advantages of the drug, the Professional Committee of Orthopedics and Traumatology Drug Research of China Association of Chinese Medicine organized experts in the fields of rheumatism, orthopedics, pharmacy and methodology in Chinese and western medicine to develop expert consensus on Chinese patent medicines in accordance with the relevant requirements of the consensus methodology. Based on full consideration of clinical research evidence and expert experience, the clinical issues were summarized in the consensus, and for those clinical problems supported by evidences, the internationally recognized recommendation evaluation and formulation method GRADE was used to evaluate the evidence and form recommendations; for those clinical issues not supported by evidences, a consensus was reached through the nominal group method to form consensus recommendations. The consensus adopted a concise and clear format to form re-commendations or reach consensus suggestions on the medication regimen, medication characteristics, intervention timing, usage and dosage, course of use and safety issues for the treatment of rheumatoid arthritis and knee osteoarthritis with Wangbi Tablets. It is suggested that its application will better improve the efficacy of Wangbi Tablets in the treatment of rheumatoid arthritis and knee osteoarthritis, at the same time provide a reference for clinicians to use Wangbi Tablets in a standardized, reasonable and safe manner.

[Meta-analysis of laboratory index of Tripterygium Glycosides Tablets in treatment of rheumatoid arthritis].

The aim of this study was to systematically evaluate the clinical efficacy of Tripterysium Glycosides Tablets( TGT) alone or in combination with methotrexate( MTX) in the treatment of rheumatoid arthritis( RA) based on the laboratory index criteria and to provide a basis for the clinical application of TGT against RA. Six databases including CNKI,Wan Fang,VIP,PubMed,EMbase and Cochrane were retrieved for randomized controlled trials( RCT) about TGT alone or combination with MTX in the treatment of RA.Then risk assessment tools were used for quality evaluation of the studies,and data extraction and analysis were conducted by using Rev Man 5.3 software for Meta-analysis. A total of 1 709 articles were retrieved,and finally 25 studies were included,with a total sample size of 2 507 cases. Meta-analysis results showed that between TGT alone and TGT alone,MDESR=-2. 66,95%CI[-8.17,2.86],P = 0.35; MDCRP=-2.38,95%CI[-9.01,4.24],P = 0.48; between TGT combined with MTX and MTX alone,MDESR= 8.74,95%CI[6.72,10.76],P<0.000 01; MDCRP= 5.37,95%CI[3.71,7.03],P<0.000 01; SMDRF= 1.05,95%CI[0.51,1.60],P = 0.000 1.The effect of TGT on decreasing CRP and ESR in RA patients was similar to the MTX. In addition,TGT combined with MTX were more effective in decreasing CRP,ESR,RF than MTX alone. However,due to the potential bias in the included studies,more and high-quality randomized controlled trials would be needed to improve the level of evidence.

Effects of lead exposure on dendrite and spine development in hippocampal dentate gyrus areas of rats.

Lead exposure has been implicated in the impairment of synaptic plasticity in the hippocampal dentate gyrus (DG) areas of rats. However, whether the degradation of physiological properties is based on the morphological alteration of granule neurons in DG areas remains elusive. Here, we examined the dendritic branch extension and spine formation of granule neurons after lead exposure during development in rats. Dendritic morphology was studied using Golgi-Cox stain method, which was followed by Sholl analysis at postnatal days 14 and 21. Our results indicated that, for both ages, lead exposure significantly decreased the total dendritic length and spine density of granule neurons in the DG of the rat hippocampus. Further branch order analysis revealed that the decrease of dendritic length was observed only at the second branch order. Moreover, there were obvious deficits in the proportion and size of mushroom-type spines. These deficits in spine formation and maturity were accompanied by a decrease in Arc/Arg3.1 expression. Our present findings are the first to show that developmental lead exposure disturbs branch and spine formation in hippocampal DG areas. Arc/Arg3.1 may have a critical role in the disruption of neuronal morphology and synaptic plasticity in lead-exposed rats.

Achyranthes bidentata extract exerts osteoprotective effects on steroid-induced osteonecrosis of the femoral head in rats by regulating RANKL/RANK/OPG signaling.

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.

Genetic association of the P-glycoprotein gene ABCB1 polymorphisms with the risk for steroid-induced osteonecrosis of the femoral head in Chinese population.

Steroid administration, which is commonly performed for the treatment of autoimmune inflammatory diseases, cancers or organ transplantation, has been a leading cause of nontraumatic osteonecrosis of the femoral head (ONFH). Single nucleotide polymorphisms (SNPs) of the adenosine triphosphate-binding cassette B1 (ABCB1) gene have been demonstrated to be related to steroid-induced ONFH in small sample sizes of Japanese kidney failure and Chinese systemic lupus erythematosus patients. However, there are obvious controversial results in the relationship of ABCB1 gene polymorphisms with steroid-induced ONFH. The aim of this study was to validate the genetic association of ABCB1 polymorphisms with the risk for steroid-induced ONFH in a large cohort of Chinese population. A case-control study was conducted, which included 94 and 106 unrelated patients after steroid administration recruited from 14 provinces in China, respectively. Two SNPs (rs1045642 and rs2032582) within ABCB1 were genotyped using Sequenom MassARRAY system. Multivariate analyses based on clinical information were performed to determine the associations between the SNPs and risk of steroid-induced ONFH. rs1045642 SNP was significantly associated with steroid-induced ONFH group in codominant (P=0.02), recessive (P=0.006) and overdominant (P=0.03) models. However, there were no differences found in genotype frequencies of rs2032582 SNP between controls and patients with steroid-induced ONFH (all P>0.05). These findings suggested that rs1045642 SNP of ABCB1 may be associated with the risk of steroid-induced ONFH. Thus, it is useful to analyze this polymorphism for identifying high-risk individuals before the administration of steroids.

Huogu I formula prevents steroid-induced osteonecrosis in rats by down-regulating PPARgamma expression and activating wnt/LRP5/ beta-catenin signaling.

OBJECTIVE: To investigate the effects of Huogu I formula on regulation of lipid metabolism in steroid-induced osteonecrosis of the femoral head (SONFH) rats and verify our hypothesis that Huogu I formula regulates lipid metabolism by down-regulating peroxisome proliferator-activated receptor gamma (PPARgamma) expression and activating Wnt signaling pathways. METHODS: Eighty-five rats were divided into four groups: control, model, Huogu 15 g/kg and Huogu 30 g/kg. Six weeks later, animals were anaesthetized, femora was dissected for histopathological examination of the osteonecrotic changes and repair processes, micro computed tomography (Micro-CT)-based micro-angiography was performed to assess vascularization. Serum lipid levels were detected by haematological examination. The expressions of PPARy, Wnt3a, low density lipoprotein receptor-related protein 5 (LRP5) and beta-catenin were evaluated by immunohistochemistry, Western blot and quantitative real-time polymerase chain reaction analyses. RESULTS: The incidence of osteonecrosis, ratio of empty lacuna, adipose tissue area and adipocyte perimeter in the bone marrow were dramatically lower in the Huogu I formula treatment groups. By micro-CT quantification, Huogu I formula treatment dose-dependently increased vessel volume, vessel surface, percentage of vessel volume and vessel thickness of the femoral heads of SONFH rats. Levels of serum lipid in Huogu 15 g/kg and Huogu 30 g/kg groups reduced significantly. Huogu I formula treatment could suppress the expression of PPARy and increase the expressions of Wnt3a, LRP5 and beta-catenin at both protein and mRNA levels. CONCLUSION: The results of our present study highlight the lipid-lowering potential of Huogu I formula, and provide further evidence of the involvement of the PPARgamma inhibition and Wnt/LRP5/ beta-catenin signaling activation in the effects of Huogu I formula.

Effect of ermiao fang with xixin (herba asari mandshurici) on bone marrow stem cell directional homing to a focal zone in an osteoarthritis rat model.

OBJECTIVE: To investigate the effects of Ermiao Fang (EM) with medical guide Xixin (Herba Asari Mandshurici) (HAM) on bone marrow stem cell migration to a focal zone in osteoarthritis (OA) rats. METHODS: OA rats were induced by arthrectomy and assigned to sham-operated, model, EM, or EM plus HAM groups. All rats were injected with recombinant human granulocyte colony-stimulating factor 30 microg x kg(-1) x d(-1) for 7 days and treated with EM or EM plus HAM at 1.6 or 1.9 g x kg(-1) x d(-1) for 3 or 6 weeks, respectively. Chondrocyte apoptosis and cartilage matrix components were tested by transferase-mediated deoxyuridine triphosphate-biotin nick end labeling assay and special staining. Levels of interleukin-1 beta (IL-1beta) tumor necrosis factor alpha (TNF-alpha) nitric oxide (NO), and inducible nitric oxide synthase (iNOS) in serum were detected by enzyme-linked immunosorbent assay or radioimmunoassay. Matrix metalloproteinases (MMPs)-13, tissue inhibitors of metalloproteinases (TIMPs)-1, Bromodeoxyuridine (BrdU), cluster of differentiation 34 (CD34), and stromal cell-derived factor 1 (SDF-1) were measured by immunohistochemical assay. RESULTS: The EM and EM plus HAM groups had significantly less cartilage damage and synovium inflammation the model group. Moreover, the EM and EM plus HAM groups had less chondrocyte apoptosis and more proteoglycan and collagen content than the model group. The EM and EM plus HAM groups had obviously higher MMPs-13 and TIMPs-1 expression in the cartilage than the model group. Moreover, the two formula groups had less release of IL-1beta, TNF-alpha, NO, and iNOS than model group. Importantly, the expressions of BrdU, CD34, and SDF-1 in cartilage were significantly higher in the EM and EM plus HAM-Medtreated rats than model group. Notably, the EM plus HAM treatment seemed to have the greatest effects. CONCLUSION: HAM improves the therapeutic effects of EM on OA rats by enhancing BMSC directional homing to the focal zone.

Ar/NH3 Plasma Etching of Cobalt-Nickel Selenide Microspheres Rich in Selenium Vacancies Wrapped with Nitrogen Doped Carbon Nanotubes as Highly Efficient Air Cathode Catalysts for Zinc-Air Batteries.

This work utilizes defect engineering, heterostructure, pyridine N-doping, and carbon supporting to enhance cobalt-nickel selenide microspheres' performance in the oxygen electrode reaction. Specifically, microspheres mainly composed of CoNiSe2 and Co9Se8 heterojunction rich in selenium vacancies (VSe·) wrapped with nitrogen-doped carbon nanotubes (p-CoNiSe/NCNT@CC) are prepared by Ar/NH3 radio frequency plasma etching technique. The synthesized p-CoNiSe/NCNT@CC shows high oxygen reduction reaction (ORR) performance (half-wave potential (E1/2) = 0.878 V and limiting current density (JL) = 21.88 mA cm-2). The JL exceeds the 20 wt% Pt/C (19.34 mA cm-2) and the E1/2 is close to the 20 wt% Pt/C (0.881 V). It also possesses excellent oxygen evolution reaction (OER) performance (overpotential of 324 mV@10 mA cm-2), which even exceeds that of the commercial RuO2 (427 mV@10 mA cm-2). The density functional theory calculation indicates that the enhancement of ORR performance is attributed to the synergistic effect of plasma-induced VSe· and the CoNiSe2-Co9Se8 heterojunction. The p-CoNiSe/NCNT@CC electrode assembled Zinc-air batteries (ZABs) show a peak power density of 138.29 mW cm-2, outperforming the 20 wt% Pt/C+RuO2 (73.9 mW cm-2) and other recently reported catalysts. Furthermore, all-solid-state ZAB delivers a high peak power density of 64.83 mW cm-2 and ultra-robust cycling stability even under bending.

Kinesitherapy for Knee Osteoarthritis Patients Physical and Psychological Health Based on "Traditional Chinese Exercise" Management Modalities: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Traditional Chinese exercise ("TCE" management modalities), including but not limited to Tai Chi, Baduanjin, and Yijinjing, has a good effect on improving the physical function of patients with knee osteoarthritis, but less attention has been paid to the impact on the psychological health of patients, and currently there is insufficient evidence to support it. We conducted this study to provide a systematic synthesis of best evidence regarding the physical and mental health of patients with knee osteoarthritis treated by traditional Chinese exercise. Literature on the effectiveness of traditional Chinese exercise (Tai Chi, Baduanjin, Yijinjing, Qigong, etc.) versus conventional therapy (muscle-strength training of the lower extremity and aerobic training, wellness education, quadriceps strengthening exercises, etc.) on Western Ontario and McMaster Universities Arthritis Index (WOMAC), visual analog scale (VAS), Short Form-36 (SF-36), Timed Up and Go Test (TUG), and Berg Balance Scale (BBS) in knee osteoarthritis (KOA) from Pubmed, Web of Science, Ovid Technologies, China National Knowledge Infrastructure (CNKI), Chinese Science and Technology Periodical Database (VIP), Wanfang Database, and SinoMed were collected from their inception to April 2022. Thirty-three studies with 2621 cases were included in this study. The study's results indicated that compared with conventional therapy, traditional Chinese exercise had more advantages on patients' WOMAC score, significantly reducing patients' overall WOMAC score (SMD = -0.99; 95% CI: -1.38, -0.60; p < 0.00001) and relieving pain (SMD = -0.76; 95% CI: -1.11, -0.40; p < 0.0001) in patients with KOA. It also has advantages over conventional therapy in improving mental component score (MCS) (SMD = 0.32; 95% CI: -0.00, 0.65; p = 0.05) and physical component score (PCS) (SMD = 0.34; 95% CI: 0.05, 0.62; p = 0.02). Compared with conventional therapy, traditional Chinese exercise can significantly reduce the effect on timed up and go test (TUG) score (SMD = -0.30; 95% CI: -0.50, -0.11; p = 0.002), beck depression inventory (DBI) score (SMD = -0.62; 95% CI: -1.03, -0.22; p = 0.002), and increase the impact on Berg Balance Scale (BBS) score (SMD = 0.60; 95% CI: 0.37, 0.83; p < 0.00001). The findings of this study indicated that traditional Chinese exercise improved body function and mental health in patients with knee osteoarthritis significantly. More high-quality clinical evidence-based data was needed to confirm the therapeutic effect of traditional Chinese exercise on the physical and mental health in KOA patients.

Osteoking promotes bone formation and bone defect repair through ZBP1-STAT1-PKR-MLKL-mediated necroptosis.

BACKGROUND: Osteoking has been used for fracture therapy with a satisfying clinical efficacy. However, its therapeutic properties and the underlying mechanisms remain elusive. METHOD: A bone defect rat model was established to evaluate the pharmacological effects of Osteoking by the dynamic observation of X-ray, micro-CT and histopathologic examination. Transcriptome profiling was performed to identify bone defect-related genes and Osteoking effective targets. Then, a "disease-related gene-drug target" interaction network was constructed and a list of key network targets were screened, which were experimentally verified. RESULTS: Osteoking effectively promoted bone defect repair in rats by accelerating the repair of cortical bone and the growth of trabeculae. Histopathologically, the bone defect rats displayed lower histopathologic scores in cortical bone, cancellous bone and bone connection than normal controls. In contrast, Osteoking exerted a favorable effect with a dose-dependent manner. The abnormal serum levels of bone turnover markers, bone growth factors and bone metabolism-related biochemical indexes in bone defect rats were also reversed by Osteoking treatment. Following the transcriptome-based network investigation, we hypothesized that osteoking might attenuate the levels of ZBP1-STAT1-PKR-MLKL-mediated necroptosis involved into bone defect. Experimentally, the expression levels of ZBP1, STAT1, PKR and the hallmark inflammatory cytokines for the end of necroptosis were distinctly elevated in bone defect rats, but were all effectively reversed by Osteoking treatment, which were also suppressed the activities of RIPK1, RIPK3 and MLKL in bone tissue supernatants. CONCLUSIONS: Osteoking may promote bone formation and bone defect repair by regulating ZBP1-STAT1-PKR axis, leading to inhibit RIPK1/RIPK3/MLKL activation-mediated necroptosis.

Synergistic Effect of Dual Phases to Improve Lithium Storage Properties of Nb2O5.

Niobium pentoxides (Nb2O5) present great potential as next-generation anode candidates due to exceptional lithium-ion intercalation kinetics, considerably high capacity, and reasonable redox potential. Although four phases of Nb2O5 including hexagonal, orthorhombic, tetragonal, and monoclinic polymorphs show diverse characteristics in electrochemical performance, stable lifetime, high specific capacity, and fast intercalation properties cannot be delivered simultaneously with a single phase. Herein, this issue is addressed by generating a homogeneous mixture of orthorhombic and monoclinic crystals at the nanoscale. Reversible lithium-ion intercalation/deintercalation of the monoclinic phase is achieved, and exceptional lithium storage sites are created at the interface of the two phases. As a result, electrochemical features of stable lifetime from the orthorhombic phase and high specific performance from the monoclinic phase are harmoniously combined. This dual-phase Nb2O5/C nanohybrids deliver as high as 380 mA h g-1 (0.01-3.0 V) and 184 mA h g-1 (1.0-3.0 V) after 200 cycles. The essential principle of property enhancement is further confirmed through in situ XRD measurements and DFT calculations. The dual-phase concept can be further applied on electrodes with multiphases to achieve high electrochemical performance.

Cartilage protective and anti-edema effects of JTF in osteoarthritis via inhibiting NCOA4-HMGB1-driven ferroptosis and aquaporin dysregulation.

BACKGROUND: Preventing joint edema is crucial in halting osteoarthritis (OA) progression. Growing clinical evidence indicate that Jianpi-Tongluo Formula (JTF) may have a promising anti-edema effect. However, the therapeutic properties of JTF and the underlying mechanisms remains unclear. MATERIALS AND METHODS: An OA rat model was established and employed to evaluate pharmacological effects of JTF in vivo based on dynamic histopathologic assessments and micro-CT observations. Then, OA-related genes and potential targets of JTF were identified through clinical transcriptomic data analysis and "disease gene-drug target" network analysis, which were verified by a series of in vivo experiments. RESULTS: JTF administration effectively reduced pain and joint edema, inhibited matrix degradation, chondrocyte apoptosis, and aquaporin expression in OA rats. Notably, JTF dose-dependently reversed damage-associated molecular patterns and inflammatory factor upregulation. Mechanically, our "disease gene-drug target" network analysis indicated that the NCOA4-HMGB1-GSK3B-AQPs axis, implicated in ferroptosis and aquaporin dysregulation, may be potentially served as a target of JTF against OA. Accordingly, JTF mitigated NCOA4, HMGB1, and GSK3B expression, oxidative stress, and iron metabolism aberrations in OA rats. Furthermore, JTF treatment significantly attenuated the aberrant upregulation of AQP1, AQP3, and AQP4 proteins observed in cartilage tissues of OA rats. CONCLUSION: Our data reveal for the first time that JTF may exert cartilage protective and anti-edema effects in osteoarthritis therapy by inhibiting NCOA4-HMGB1-driven ferroptosis and aquaporin dysregulation.