OBJECTIVE To investigate the effects and potential mechanism of Qiangxin decoction on mitochondrion of rats with chronic heart failure （CHF）. METHODS The CHF model was established by ligating the left anterior descending branch of the coronary artery. Modeled rats were divided into model group， Qiangxin decoction low-dose and high-dose groups （12.25， 24.50 g/kg， calculated by crude drug）， and chemical medicine group （Sacubitril valsartan sodium tablets， 10.42 mg/kg）， with 10 rats in each group； control group was set up without treatment. Each group of rats was orally administered with the corresponding medication or normal saline twice a day for 28 consecutive days. After the last medication， the contents of N-terminal pro-brain natriuretic peptide （NT-proBNP） and adenosine triphosphate （ATP） in serum and phosphatidic acid （PA） and cardiolipin （CL） in myocardial tissue were all detected； the pathological damage and collagen fibrosis of rat myocardial tissue were observed； the apoptosis of myocardial cells was determined； the ultrastructure of myocardial tissue was observed； the protein expressions of mitofusin 1 （Mfn1）， Mfn2， optic atrophy protein 1 （OPA1） and dynamin-related protein 1 （Drp1） were all detected in myocardial tissue. RESULTS Compared with control group，the serum content of NT-proBNP， apoptotic rate of myocardial cells， and relative expressions of S-OPA1 and Drp1 proteins were all increased significantly； serum content of ATP，contents of PA and CL， and relative expressions of Mfn1， Mfn2 and L-OPA1 proteins were all significantly reduced （P＜0.05）. There were abnormal membrane tissue structure in various layers of myocardial tissue， degeneration and necrosis of myocardial cells， and severe fibrosis； the mitochondria were swollen， with reduced or absent cristae， and uneven matrix density. After intervention with Qiangxin decoction， the levels of the aforementioned quantitative indicators in serum and myocardial tissue of rats （excluding CL content in the Qiangxin decoction low- dose group） were significantly reversed （P＜0.05）； the pathological damage of myocardial tissue had significantly improved， fibrosis had significantly reduced， mitochondrial morphology tended to be normal， cristae had increased， and matrix density was uniform. CONCLUSIONS Qiangxin decoction can regulate myocardial mitochondrial function and structural integrity of CHF rats， thereby improving myocardial energy metabolism and antagonizing myocardial fibrosis， the mechanism of which may be associated with activating PA/Mfn/CL signaling pathway.

OBJECTIVE To investigate the effects and potential mechanism of Qiangxin decoction on mitochondrion of rats with chronic heart failure （CHF）. METHODS The CHF model was established by ligating the left anterior descending branch of the coronary artery. Modeled rats were divided into model group， Qiangxin decoction low-dose and high-dose groups （12.25， 24.50 g/kg， calculated by crude drug）， and chemical medicine group （Sacubitril valsartan sodium tablets， 10.42 mg/kg）， with 10 rats in each group； control group was set up without treatment. Each group of rats was orally administered with the corresponding medication or normal saline twice a day for 28 consecutive days. After the last medication， the contents of N-terminal pro-brain natriuretic peptide （NT-proBNP） and adenosine triphosphate （ATP） in serum and phosphatidic acid （PA） and cardiolipin （CL） in myocardial tissue were all detected； the pathological damage and collagen fibrosis of rat myocardial tissue were observed； the apoptosis of myocardial cells was determined； the ultrastructure of myocardial tissue was observed； the protein expressions of mitofusin 1 （Mfn1）， Mfn2， optic atrophy protein 1 （OPA1） and dynamin-related protein 1 （Drp1） were all detected in myocardial tissue. RESULTS Compared with control group，the serum content of NT-proBNP， apoptotic rate of myocardial cells， and relative expressions of S-OPA1 and Drp1 proteins were all increased significantly； serum content of ATP，contents of PA and CL， and relative expressions of Mfn1， Mfn2 and L-OPA1 proteins were all significantly reduced （P＜0.05）. There were abnormal membrane tissue structure in various layers of myocardial tissue， degeneration and necrosis of myocardial cells， and severe fibrosis； the mitochondria were swollen， with reduced or absent cristae， and uneven matrix density. After intervention with Qiangxin decoction， the levels of the aforementioned quantitative indicators in serum and myocardial tissue of rats （excluding CL content in the Qiangxin decoction low- dose group） were significantly reversed （P＜0.05）； the pathological damage of myocardial tissue had significantly improved， fibrosis had significantly reduced， mitochondrial morphology tended to be normal， cristae had increased， and matrix density was uniform. CONCLUSIONS Qiangxin decoction can regulate myocardial mitochondrial function and structural integrity of CHF rats， thereby improving myocardial energy metabolism and antagonizing myocardial fibrosis， the mechanism of which may be associated with activating PA/Mfn/CL signaling pathway.

Portal vein embolization （PVE） can induce atrophy of the embolized lobe and compensatory regeneration of the non-embolized lobe. However， due to inadequate regeneration of future liver remnant （FLR） after PVE， some patients remain unsuitable for hepatectomy after PVE. In recent years， liver venous deprivation （LVD）， which combines PVE with hepatic vein embolization （HVE）， has induced enhanced FLR regeneration. Compared with associating liver partition and portal vein ligation for staged hepatectomy （ALPPS）， LVD triggers faster and more robust FLR regeneration， with lower incidence rate of postoperative complications and mortality rate. By reviewing related articles on LVD， this article introduces the effectiveness of LVD and analyzes the differences and safety of various technical paths， and it is believed that LVD is a safe and effective preoperative pretreatment method.

ObjectiveMagnetoencephalography (MEG), a non-invasive neuroimaging technique, meticulously captures the magnetic fields emanating from brain electrical activity. Compared with MEG based on superconducting quantum interference devices (SQUID), MEG based on optically pump magnetometer (OPM) has the advantages of higher sensitivity, better spatial resolution and lower cost. However, most of the current studies are clinical studies, and there is a lack of animal studies on MEG based on OPM technology. Pain, a multifaceted sensory and emotional phenomenon, induces intricate alterations in brain activity, exhibiting notable sex differences. Despite clinical revelations of pain-related neuronal activity through MEG, specific properties remain elusive, and comprehensive laboratory studies on pain-associated brain activity alterations are lacking. The aim of this study was to investigate the effects of inflammatory pain (induced by Complete Freund’s Adjuvant (CFA)) on brain activity in a rat model using the MEG technique, to analysis changes in brain activity during pain perception, and to explore sex differences in pain-related MEG signaling. MethodsThis study utilized adult male and female Sprague-Dawley rats. Inflammatory pain was induced via intraplantar injection of CFA (100 μl, 50% in saline) in the left hind paw, with control groups receiving saline. Pain behavior was assessed using von Frey filaments at baseline and 1 h post-injection. For MEG recording, anesthetized rats had an OPM positioned on their head within a magnetic shield, undergoing two 15-minute sessions: a 5-minute baseline followed by a 10-minute mechanical stimulation phase. Data analysis included artifact removal and time-frequency analysis of spontaneous brain activity using accumulated spectrograms, generating spectrograms focused on the 4-30 Hz frequency range. ResultsMEG recordings in anesthetized rats during resting states and hind paw mechanical stimulation were compared, before and after saline/CFA injections. Mechanical stimulation elevated alpha activity in both male and female rats pre- and post-saline/CFA injections. Saline/CFA injections augmented average power in both sexes compared to pre-injection states. Remarkably, female rats exhibited higher average spectral power 1 h after CFA injection than after saline injection during resting states. Furthermore, despite comparable pain thresholds measured by classical pain behavioral tests post-CFA treatment, female rats displayed higher average power than males in the resting state after CFA injection. ConclusionThese results imply an enhanced perception of inflammatory pain in female rats compared to their male counterparts. Our study exhibits sex differences in alpha activities following CFA injection, highlighting heightened brain alpha activity in female rats during acute inflammatory pain in the resting state. Our study provides a method for OPM-based MEG recordings to be used to study brain activity in anaesthetized animals. In addition, the findings of this study contribute to a deeper understanding of pain-related neural activity and pain sex differences.

Objective: We aimed to explore the mechanism of Pizhan Powder in regulating the Wnt4/β-catenin signaling pathway to promote wound healing in mice with chronic skin ulcer. Methods: Male BALB/c mice were divided into blank, model, Pizhan Powder, Pizhan powder removed bark medications, bark medications, inhibitor, and Pizhan Powder + inhibitor groups using the random number table method, with six mice per group. Except for the blank group, chronic skin ulcer wound models were prepared in the other groups by implanting foreign bodies. The blank control group received no treatment, whereas the wounds of the model group were cleaned with furacilin solution. The Pizhan Powder, Pizhan Powder removed bark medications, and bark medications groups were each administered 0.1 g of the corresponding medication on the skin wounds. The inhibitor group received an intraperitoneal injection of 3-(4-methylphenylsulfonamido) benzoic acid methyl ester (MSAB) at a dosage of 10 mg/kg. The Pizhan Powder + inhibitor group was administered 0.1 g of Pizhan Powder on the skin wound, and an intraperitoneal injection of MSAB was also administered (10 mg/kg). These treatments were administered once a day for 14 consecutive days. Wound healing was observed on the first, third, seventh, and 14th day of treatment; hematoxylin and eosin staining was used to observe the pathological changes of ulcerated skin; keratin 10 (CK10), keratin 14 (CK14), cell proliferation nuclear antigen (Ki-67), α-smooth muscle actin (α-SMA), and β-catenin expression in wounds was observed through immunofluorescence; Western blotting was used to detect the expression of signaling pathway-related proteins (Wnt4 and β-catenin). Results: Compared to the model group, the Pizhan Powder group showed a reduced wound area and an increased wound healing rate (P<0.05) and elevated CK10, CK14, Ki-67, α-SMA, β-catenin, and Wnt4 protein expressions (P<0.05). Compared to the Pizhan Powder group, the wound healing rate of the bark medications and Pizhan Powder removed bark medications groups was reduced (P<0.05). The wound healing rate and the fluorescence expression of CK10, CK14, Ki-67, and α-SMA in the Pizhan Powder removed bark medications group were lower than that in the bark medications group (P<0.05). Compared to the Pizhan Powder group, the wound healing rate of the Pizhan Powder + inhibitor group was reduced, and CK10, CK14, Ki-67, α-SMA, β-catenin and Wnt4 protein expression were lower (P<0.05). Conclusion Pizhan Powder promotes wound healing in chronic skin ulcers of mice by regulating the Wnt4/β-catenin signaling pathway. The bark medications (buffalo hide, white mulberry root-bark, and Chinese wolfberry root-bark) play a crucial role, representing a concrete application of the traditional Chinese medicine theory of " treating skin with skin.

BACKGROUND:It has been found that abnormal apoptosis of bone tissue cells induced by abnormal iron metabolism plays an important role in the progression of osteoporosis. OBJECTIVE:To investigate the effect of naringin on iron metabolism and cell apoptosis in bone tissue of rats with osteoporosis. METHODS:Fifty 2-month-old female Sprague-Dawley rats were randomly divided into five groups with 10 rats in each group:sham group,osteoporosis group,naringin low-dose group,naringin high-dose group,and naringin high-dose+DKK-1 group.Except for the sham group,rat models of osteoporosis were established by removing bilateral ovarian tissues in the other groups.At 8 weeks after modeling,rats in the naringin low-and high-dose groups were given 100 and 400 mg/kg/d naringenin by gavage,respectively,and rats in the naringenin high dose+DKK-1 group were given 400 mg/kg/d naringin by gavage and subcutaneous injection of 25 mg/kg/d DKK-1,an inhibitor of the Wnt1 signaling pathway,for 7 consecutive days.Relevant indexes were detected after administration. RESULTS AND CONCLUSION:Compared with the osteoporosis group,naringin could enhance the bone mineral density and serum calcium and superoxide dismutase levels in rats(P<0.05),and reduce the serum levels of osteocalcin,malondialdehyde,and phosphorus(P<0.05),while DKK-1 could partially inhibit the interventional effect of naringin(P<0.05).Results from Micro-CT scanning,hematoxylin-eosin and TUNEL staining showed that compared with the osteoporosis group,naringin significantly improved bone microstructure and reduced the rate of cell apoptosis,while DKK-1 partially inhibited the interventional effect of naringin.Immunofluorescence staining results showed that compared with the osteoporosis group,naringin could reduce the oxygen content,anti-tartaric acid phosphatase expression,and elevate the expression of alkaline phosphatase in active tibia tissues(P<0.05),while DKK-1 could partially inhibit the interventional effect of naringin(P<0.05).Results from Prussian blue staining and immunohistochemical staining showed that compared with the osteoporosis group,naringin reduced iron deposition in bone and liver tissues as well as the expression of transferrin receptor 1(P<0.05),and elevated the protein expression of ferroportin 1(P<0.05)in bone tissue,and DKK-1 partially inhibited the intervention of naringin(P<0.05).PCR and western blot assay of tibia specimens showed that compared with the osteoporosis group,naringin decreased the expression of anti-tartrate acid phosphatase,transferrin receptor 1 and Bax(P<0.05),and elevated the expression of alkaline phosphatase,ferroportin 1,Bcl-2,Wnt1 and β-catenin(P<0.05),while DKK-1 partially inhibited the interfering effect of naringin(P<0.05).To conclude,naringin inhibits the progression of osteoporosis by reducing iron deposition and apoptosis rate in bone tissue,which may be related to the activation of the Wnt1 signaling pathway.

BACKGROUND:Although researchers have noted that fibroblast growth factor receptor 1 shows great potential in rheumatoid arthritis bone destruction,there is a lack of reviews related to the potential mechanisms of fibroblast growth factor receptor 1 in rheumatoid arthritis bone destruction. OBJECTIVE:To comprehensively analyze the mechanism of fibroblast growth factor receptor 1 in bone destruction in rheumatoid arthritis by reviewing the relevant literature at both home and abroad. METHODS:We searched the CNKI database using the Chinese search terms"fibroblast growth factor receptor 1,rheumatoid arthritis,bone destruction,bone cells,osteoblasts,osteoclasts,chondrocytes,macrophages,synovial fibroblasts,T cells,vascular endothelial cells."PubMed database was searched using the English search terms"fibroblast growth factor receptor 1,rheumatoid arthritis,bone destruction,osteocytes,osteoblasts,osteoclasts,chondrocytes,macrophages,synovial fibroblasts,T cells,endothelial cells."The search period focused on April 1992 to January 2024.After screening the literature by reading titles,abstracts,and full texts,a total of 82 articles were finally included for review according to inclusion and exclusion criteria. RESULTS AND CONCLUSION:Fibroblast growth factor receptor 1 was found to be widely expressed in bone tissue-associated cells,including osteoblasts,osteoclasts,and osteoclasts.Fibroblast growth factor receptor 1 affects bone remodeling and homeostasis by regulating the function of these cells,as well as promoting the onset and progression of bone destruction in rheumatoid arthritis.Fibroblast growth factor receptor 1 is involved in the inflammatory response of synovial fibroblasts and macrophages and regulates angiogenesis of endothelial cells in synovial tissues.Fibroblast growth factor receptor 1 promotes bone destruction in several ways.Fibroblast growth factor receptor 1 may be a potential causative agent of bone destruction in rheumatoid arthritis and provides a reference for further research on its therapeutic targets.

BACKGROUND:Titanium implants are widely used in clinical practice because of their high strength and good biocompatibility.However,during implantation,bacterial infection and tissue damage environment produce a large number of reactive oxygen species,which can easily lead to delayed tissue healing and surgical failure.Consequently,the development of titanium implants with antimicrobial and antioxidant properties becomes paramount. OBJECTIVE:Considering the potent antimicrobial attributes of copper ions and the remarkable antioxidant qualities of polyphenols,we proposed the fabrication of polyphenol-mediated copper ion coatings on titanium surfaces.These coatings were subsequently assessed for their in vitro antimicrobial and antioxidant properties. METHODS:Nanostructures were generated on the titanium surface using the alkali thermal method.The titanium was immersed in a solution containing tannic acid and copper ions to achieve polyphenol-mediated copper ion coatings.The surface morphology and water contact angle were detected.The loading and release of copper ions were examined using atomic absorption spectroscopy.Staphylococcus aureus was inoculated on the surface of pure titanium sheet(blank group),alkali heat treated titanium sheet(control group),and polyphenol mediated copper ion modified titanium sheet(experimental group)to observe the bacterial survival status.Osteoblast precursor cells MC3T3-E1 were co-cultivated on the surface of three groups of titanium sheets to assess their antioxidant properties and bioactivity. RESULTS AND CONCLUSION:(1)Scanning electron microscopy showed that the polyphenol-mediated copper ion modified titanium sheet had rod-like nanostructures and no cracks on the surface.The surface hydrophilicity of copper ion modified titanium sheet mediated by polyphenol was close to that of pure titanium sheet.Atomic absorption spectrometry results showed a 51%increase in the loading capacity of copper ions after polyphenol mediation,with a uniform release of copper ions.(2)The antibacterial rates of titanium sheets in the blank group,control group,and experimental group were 0%,21.65%,and 93.75%,respectively.The live/dead staining and CTC staining showed that the live bacteria on the surface of titanium plates in the blank group were the most,and the live bacteria on the surface of titanium plates in the experimental group were the least.(3)The results of live/dead staining and CCK-8 assay showed that the three groups of titanium sheets had good cytocompatibility,and the titanium sheets in the experimental group were more conducive to the proliferation of MC3T3-E1 cells.Active oxygen fluorescence probe detection exhibited that compared with the other two groups,the fluorescence intensity of active oxygen on the surface of the experimental group was significantly reduced.The results of alkaline phosphatase and alizarin red S staining showed that the osteogenic differentiation and extracellular matrix mineralization of MC3T3-E1 cells on the surface of titanium sheets in the experimental group were stronger than those in the other two groups.(4)These results show that the polyphenol-mediated copper ion coating has strong antibacterial and antioxidant properties and promotes osteogenic differentiation.

BACKGROUND:The guinea pig is considered to be the most useful spontaneous model for evaluating primary osteoarthritis in humans because of its similar knee joint structure and close histopathologic features to those of humans. OBJECTIVE:To investigate the pathological process of spontaneous knee osteoarthritis in guinea pigs by analyzing the histopathology of the total knee joint of guinea pigs aged 1 to 18 months. METHODS:Eight healthy female Hartley guinea pigs in each age group of 1,6,10,14,16,and 18 months old were selected.The quadriceps femoris was taken for hematoxylin-eosin staining,and the total knee joint was stained with hematoxylin-eosin and toluidine blue.The histopathology of the cartilage,subchondral bone,synovium,meniscus,and muscles were observed under light microscope.Mankin's score and synovitis score were compared,and the correlation analysis was conducted. RESULTS AND CONCLUSION:As the guinea pig age increased,the Mankin's score increased(P<0.05),and the pathological score of synovitis also gradually increased(P<0.05),and there was a significant positive correlation between the two(r=0.641,P<0.001).The incidence rate of subchondral bone marrow lesion in 18-month-old guinea pigs was 50%,and the incidence of meniscus injury was 37.5%.In addition,osteophyte and narrowing of the joint space were observed,and only a few guinea pigs had inflammation in the quadriceps femoris.To conclude,guinea pigs develop significant cartilage defects,synovial inflammation,subchondral bone lesions,meniscus injury,osteophyte formation,and joint space narrowing as they age,all of which are similar to the pathological processes of primary knee osteoarthritis in humans,making it an ideal model of spontaneous knee osteoarthritis.

Objective: To evaluate the long-term efficacy and safety of low-intensity extracorporeal shock wave therapy (Li-ESWT) for refractory prostate-pelvic syndrome (PPS). Methods: Clinical data of 173 patients with refractory PPS undergoing Li-ESWT at our hospital during Jan.2020 and Jan.2023 were retrospectively analyzed.All patients received weekly treatment for 8 consecutive weeks.Changes in the National Institutes of Health chronic prostatitis symptom index (NIH-CPSI)，international prostate symptom score (IPSS)，visual analog scale (VAS)，and international index of erectile function-5 (IIEF-5) were compared before treatment，immediately，1，3，and 6 months after treatment. Results: A total of 142 patients (82.1%) completed all follow-ups.Compared to baseline data，there was a statistically significant improvement in NIH-CPSI，IPSS，VAS，and IIEF-5 scores immediately after treatment and 1，3，and 6 months after treatment (P<0.01).No significant adverse reactions or complications were observed throughout the follow-up.At the time of treatment completion，115 patients (81.0%) had a decrease of ≥6 in NIH-CPSI; 99 patients (69.7%) had a decrease of ≥3 in IPSS; 121 patients (85.2%) had a decrease of ≥3 in VAS; 105 patients (73.9%) had an increase of ≥4 in IIEF-5.At the 6-month follow-up，patients who responded to treatment maintained satisfactory therapeutic effects. Conclusion: Li-ESWT can significantly improve clinical symptoms and quality of life for patients with refractory PPS，with therapeutic effects lasting at least 6 months.