BACKGROUND:Bone relies on the close connection between blood vessels and bone cells to maintain its integrity.Bones are in a physiologically hypoxic environment.Therefore,the study of angiogenesis and osteogenesis in hypoxic environment is closer to the microenvironment in vivo. OBJECTIVE:To explore the influence of Wenshen Tongluo Zhitong(WSTLZT)formula on H-type bone microvascular endothelial cell/bone marrow mesenchymal stem cell co-culture system in hypoxia environment and its related mechanism. METHODS:Enzyme digestion method and flow sorting technique were used to isolate and identify H-type bone microvascular endothelial cells.Mouse bone marrow mesenchymal stem cells were isolated and obtained by bone marrow adhesion method.H-type bone microvascular endothelial cell/bone marrow mesenchymal stem cell hypoxic co-culture system was established using Transwell chamber and anoxic culture workstation.WSTLZT formula powder was used to intervene in each group at a mass concentration of 50 and 100 μg/mL.The angiogenic function of H-type bone microvascular endothelial cells in the co-culture system was evaluated by scratch migration test and tube formation test.The osteogenic differentiation ability of bone marrow mesenchymal stem cells in the co-cultured system was evaluated by alkaline phosphatase staining and alizarin red staining.The protein and mRNA expression changes of PDGF/PI3K/AKT signal axis related molecules in H-type bone microvascular endothelial cells in the co-cultured system were detected by Western Blotting and q-PCR,respectively. RESULTS AND CONCLUSION:(1)Compared with the normal oxygen group,the scratch mobility and new blood vessel length of H-type bone microvascular endothelial cells were significantly higher(P<0.05);the osteogenic differentiation capacity of bone marrow mesenchymal stem cells was higher(P<0.05);the expression of PDGF/PI3K/AKT axis-related molecular protein and mRNA increased(P<0.05)in the hypoxia group.(2)Compared with the hypoxia group,scratch mobility and new blood vessel length were significantly increased in the H-type bone microvascular endothelial cells(P<0.05);bone marrow mesenchymal stem cells had stronger osteogenic function(P<0.05);the expression of PDGF/PI3K/AKT axis-related molecular proteins and mRNA further increased(P<0.05)after treatment with different dose concentrations of WSTLZT formula.These findings conclude that H-type angiogenesis and osteogenesis under hypoxia may be related to the PDGF/PI3K/AKT signaling axis,and WSTLZT formula may promote H-type vasculo-dependent bone formation by activating the PDGF/PI3K/AKT signaling axis,thereby preventing and treating osteoporosis.

BACKGROUND:Black phosphorus has a high degree of homology with human bone,so it has been extensively studied in the field of bone tissue engineering in recent years.Since 2014,two-dimensional black phosphorus materials have garned significant attention in the field of biomedicine due to their excellent exceptional physical,chemical,and biological properties. OBJECTIVE:To summarize the advancements made in black phosphorus-based nanomaterials for bone tissue engineering,focus on the synthesis methods,osteogenic characteristics,and applications in biomaterials pertaining to two-dimensional black phosphorus nanomaterials. METHODS:Chinese and English key words were"black phosphorus,bone tissue engineering,bone defect,bone regeneration,osteogenesis."Relevant articles in PubMed and CNKI databases from January 2014 to December 2023 were searched.After exclusion and screening,96 articles were analyzed. RESULTS AND CONCLUSION:Black phosphorus nanomaterials play an important role in bone tissue engineering due to their good biocompatibility,biodegradability,photothermal action,antibacterial ability,drug loading performance,and special osteogenic effect,and are ideal candidate materials for promoting bone regeneration.The preparation of black phosphorus nanomaterials is mainly a top-down top-layer stripping method.The main principle is to weaken the van der Waals force between the black phosphorus layers by physical or chemical means to obtain a single or less layer of phosphanse,that is,black phosphorus nanosheets or quantum dots.Black phosphate-based nanocomposites are mainly divided into hydrogels,3D printing scaffolds,composite scaffolds,electrospinning,bionic periosteum,microspheres,and bionic coatings.The research of nano-black phosphorus in bone tissue engineering is in its infancy,and still faces many challenges:the behavior of black phosphorus in vivo and the interaction mechanism with various biomolecules need to be further studied.The long-term potential toxicity of black phosphorus is unknown.The manufacturing process for black phosphorus is difficult to control.Therefore,how to develop uniform size,safe,reliable,and efficient nano black phosphorus and transform it into clinical application requires interdisciplinary research on modern biomedical technology,physicochemical technology,and precision manufacturing technology.

ObjectiveIn nature, objects cast shadows due to illumination, forming the basis for stereoscopic perception. Birds need to adapt to changes in lighting (meaning they can recognize stereoscopic shapes even when shadows look different) to accurately perceive different three-dimensional forms. However, how neurons in the key visual brain area in birds handle these lighting changes remains largely unreported. In this study, pigeons (Columba livia) were used as subjects to investigate how neurons in pigeon’s ventrolateral mesopallium (MVL) represent stereoscopic shapes consistently, regardless of changes in lighting. MethodsVisual cognitive training combined with neuronal recording was employed. Pigeons were first trained to discriminate different stereoscopic shapes (concave/convex). We then tested whether and how light luminance angle and surface appearance of the stereoscopic shapes affect their recognition accuracy, and further verify whether the results rely on specify luminance color. Simultaneously, neuronal firing activity of neurons was recorded with multiple electrode array implanted from the MVL during the presentation of difference shapes. The response was finally analyzed how selectively they responded to different stereoscopic shapes and whether their selectivity was affected by the changes of luminance condition (like lighting angle) or surface look. Support vector machine (SVM) models were trained on neuronal population responses recorded under one condition (light luminance angle of 45°) and used to decode responses under other conditions (light luminance angle of 135°, 225°, 315°) to verify the invariance of responses to different luminance conditions. ResultsBehavioral results from 6 pigeons consistently showed that the pigeons could reliably identify the core 3D shape (over 80% accuracy), and this ability wasn’t affected by changes in light angle or surface appearance. Statistical analysis of 88 recorded neurons from 6 pigeons revealed that 83% (73/88) showed strong selectivity for specific 3D shapes (selectivity index>0.3), and responses to convex shapes were consistently stronger than to concave shapes. These shape-selective responses remained stable across changes in light angle and surface appearance. Neural patterns were consistent under both blue and orange lighting. The decoding accuracy achieves above 70%, suggesting stable responses under different conditions (e.g., different lighting angles or surface appearance). ConclusionNeurons in the pigeon MVL maintain a consistent neural encoding pattern for different stereoscopic shapes, unaffected by illumination or surface appearance. This ensures stable object recognition by pigeons in changing visual environments. Our findings provide new physiological evidence for understanding how birds achieve stable perception (“invariant neural representations”) while coping with variations in the visual field.

Network pharmacology and molecular docking were employed to predict the mechanism of Zhizhu Decoction in regulating macrophage polarization to reduce adipose tissue inflammation in obese children, and animal experiments were then carried out to validate the prediction results. The active ingredients and targets of Zhizhu Decoction were retrieved from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP). The inflammation related targets in the adipose tissue of obese children were searched against GeneCards, OMIM, and DisGeNET, and a drug-disease-target network was established. STRING was used to construct a protein-protein interaction(PPI) network and screen for core targets. R language was used to carry out Gene Ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analyses. AutoDock was used for the molecular docking between core targets and active ingredients. 24 SPF grade 6-week C57B/6J male mice were adaptively fed for 1 week, and 8 mice were randomly selected as the blank group. The remaining 16 mice were fed with high-fat diet for 8 weeks to onstruct a high-fat diet induced mouse obesity model. After successful modeling, the 16 mice were randomly divided into model group and Zhizhu Decoction group, with 8 mice in each group. Zhizhu Decoction group was intervened by gavage for 14 days, once a day. Blank group and model group were given an equal amount of sterile double distilled water(ddH_2O) by gavage daily. After the last gavage, serum and inguinal adipose tissue were collected from mice for testing. The morphology of inguinal adipose tissue was observed by hematoxylin-eosin(HE) staining, the levels of inflammatory factors interleukin-6(IL-6) and tumor necrosis factor-α(TNF-α)were detected by enzyme-linked immunosorbent assay(ELISA), and the protein expression of macrophage marker molecule nitric oxide synthase(iNOS) and epidermal growth factor like hormone receptor 1(F4/80) was detected by immunofluorescence staining. Network pharmacology predicted luteolin, naringenin, and nobiletin as the main active ingredients in Zhizhu Decoction and 15 core targets. KEGG pathway enrichment analysis revealed involvement in the key signaling pathway of nuclear factor κB(NF-κB). Molecular docking showed that the active ingredients of Zhizhu Decoction bound well to the core targets. Animal experiment showed that compared with the model group, Zhizhu Decoction reduced the distribution of inflammatory cytokines in the inguinal adipose tissue of mice, lowered the levels of TNF-α and IL-6 in the serum(P<0.05, P<0.01), and down-regulated the expression of iNOS and F4/80(P<0.05). The results showed that the active ingredients in Zhizhu Decoction, such as luteolin, naringenin, and nobiletin, inhibit the aggregation of macrophages in adipose tissue, downregulate their classic activated macrophage(M1) polarization, reduce the expression of inflammatory factors IL-6 and TNF-α, and thus improve adipose tissue inflammation in obese mice.
Animals ; Drugs, Chinese Herbal/pharmacology* ; Molecular Docking Simulation ; Adipose Tissue/immunology* ; Mice ; Male ; Humans ; Network Pharmacology ; Macrophages/immunology* ; Mice, Inbred C57BL ; Child ; Protein Interaction Maps/drug effects* ; Obesity/genetics* ; Inflammation/drug therapy*

The chemical constituents were systematically separated from the roots of Berberis polyantha by various chromatographic methods, including silica gel column chromatography, HP20 column chromatography, polyamide column chromatography, reversed-phase C_(18) column chromatography, and preparative high-performance liquid chromatography. The structures of the compounds were identified by physicochemical properties and spectroscopic techniques(1D NMR, 2D NMR, UV, MS, and CD). Four phenylpropanoids were isolated from the methanol extract of the roots of B. polyantha, and they were identified as(2R)-1-(4-hydroxy-3,5-dimethoxyphenyl)-1-propanone-O-β-D-glucopyranoside(1), methyl 4-hydroxy-3,5-dimethoxybenzoate(2),(+)-syringaresinol(3), and syringaresinol-4-O-β-D-glucopyranoside(4). Compound 1 was a new compound, and other compounds were isolated from this plant for the first time. The anti-inflammatory activity of these compounds was evaluated based on the release of nitric oxide(NO) in the culture of lipopolysaccharide(LPS)-induced RAW264.7 macrophages. At a concentration of 10 μmol·L~(-1), all the four compounds inhibited the LPS-induced release of NO in RAW264.7 cells, demonstrating potential anti-inflammatory properties.
Plant Roots/chemistry* ; Animals ; Mice ; Berberis/chemistry* ; RAW 264.7 Cells ; Macrophages/immunology* ; Drugs, Chinese Herbal/isolation & purification* ; Nitric Oxide/metabolism* ; Molecular Structure ; Anti-Inflammatory Agents/isolation & purification*

OBJECTIVE: To evaluate the short-term clinical efficacy of external fixation and internal fixation with steel plate in the treatment of unstable distal radius fractures (AO-23C type), based on the principles of Chinese osteosynthesis (CO). METHODS: Forty-eight patients with unstable distal radius fractures between January 2022 and February 2023 were retrospectively analyzed and divided into the CO external fixation group and internal fixation group. CO external fixation group consisted of 25 patients, including 7 males and 18 females, aged from 37 to 56 years old with an average of ( 52.6±11.3) years old. Among them, there were 7 patients of traffic accidents and 18 patients of falls, resulting in a total of 25 patients of closed fractures and no open fractures, the treatment was conducted using closed reduction and CO external fixation. The internal fixation group consisted of 23 patients, comprising 8 males and 15 females, age ranged from 41 to 59 years old, with an average age of(53.3±13.7) years old. Among them, 8 patients resulted from car accidents while the remaining 15 patients were caused by falls. All 23 patients were closed fractures without any open fractures observed. The technique of open reduction and internal fixation with steel plate was employed. The perioperative data, including injury-operation time, operation duration, blood loss, and length of hospital stay, were assessed in both groups. Additionally, the QuickDASH score and visual analogue scale (VAS) were evaluated. Range of motion and grip strength assessment, imaging findings such as palmar inclination angle, ulnar declination angle, radius length, articular surface step, intra-articular space measurements were also examined along with any complications. RESULTS: The follow-up duration ranged from 0 to 24 months, with an average duration of (16.0±3.8) months. The CO external fixation exhibited significantly shorter time from injury to operation (2.4±3.3) d vs (7.4±3.7) d, shorter operation duration (56.27±15.23) min vs (74.10±5.26) min, lower blood loss (14.52±6.54) ml vs (32.32±10.03) ml, and reduced hospitalization days (14.04±3.24 )d vs (16.45±3.05) d compared to the internal fixation group (P<0.05). The QuickDASH score at 12 months post-operation was (8.21±1.64) in the CO external fixation group, while no significant difference was observed in the internal fixation group (7.04±3.64), P>0.05. There were no statistically significant differences in VAS between two groups at 6 weeks, as well as 1 and 3 months post-surgery (P>0.05). Additionally, there were no significant disparities observed in terms of range of motion and grip strength between two groups at the 2-year follow-up after the operation (P>0.05). After 12 months of surgery, the CO external fixation group exhibited a significantly smaller palmar inclination angle (17.90±2.18) ° vs (19.87±3.21) °, reduced articular surface step (0.11±0.03) mm vs (0.17±0.02) mm, and shorter radius length (8.16±1.11) mm compared to the internal fixation group (9.59±1.02) mm, P<0.05. The ulnar deviation angle and intra-articular space did not show any significant difference between two groups (P>0.05). The reduced fell within the allowable range between the CO external fixation group (23 out of 25 cases) and the internal fixation group (21 out of 23 cases) was not statistically significant (P=0.29). There was no significant difference in complications between the two groups(P>0.05). CONCLUSION Both the CO external fixation and open reduction with plate internal fixation demonstrate clinical efficacy in managing unstable distal radius fractures. The CO external fixation offers advantages in shorter injury-to-operation times, reduced intraoperative blood loss, and decreased surgical durations, while radial shortening is more effectively controlled by internal fixation.
Humans ; Male ; Female ; Middle Aged ; Radius Fractures/physiopathology* ; Adult ; Bone Plates ; Fracture Fixation, Internal/methods* ; External Fixators ; Retrospective Studies ; Fracture Fixation/methods* ; Wrist Fractures

OBJECTIVE: To investigate the effect of laparoscopic high ligation of spermatic cord vein in patients with chronic prostatitis and varicocele prostatitis. METHODS: A total of 90 varicocele patients were selected from January 2016 to December 2020, including 33 patients with chronic prostatitis. Changes of white blood cell count, National Institutes of Health chronic prostatitis symptom index (NIH-CPSI) score and serum testosterone level in the expressed prostate secretion (EPS) were observed before and after the operation of laparoscopic high ligation of spermatic vein. RESULTS: All patients were followed up three months after the surgery. There was no significant difference in the white blood cell counts in EPS, NIH-CPSI score, and serum testosterone level in patients with varicocele-only who underwent high ligation surgery after the operation. However, the white blood cell count in the EPS of patients with chronic prostatitis was lower than that before 3 months of operation ( ［12.39±4.23］×109/L vs ［21.36±5.05］×109/L). The NIH-CPSI score was significantly lower than that before operation ( ［12.71±6.21］ vs ［26.76±8.43］). And the serum testosterone level was higher than that before operation (［4.34±1.77］ng/ml vs ［2.36±1.05］ng/ml). CONCLUSION Laparoscopic high ligation of the spermatic vein in patients with chronic prostatitis and varicocele could effectively reduce the number of white blood cells in the EPS, boost the level of serum testosterone and improves symptoms of chronic prostatitis.
Male ; Humans ; Varicocele/surgery* ; Prostatitis/blood* ; Ligation ; Spermatic Cord/blood supply* ; Testosterone/blood* ; Chronic Disease ; Prostate/metabolism* ; Veins/surgery* ; Leukocyte Count ; Leukocytes ; Laparoscopy ; Adult

OBJECTIVE To study the intervention effects of Wenshen Tongluo Zhitong Recipe(WTZR)on macrophage senes-cence and senile osteoporosis.METHODS The senescent macrophage model was established using hydrogen peroxide(H2 O2)and subsequently divided into four groups:control,model,low-dose drug-treated serum,and high-dose drug-treated serum.β-galactosidase staining,Western blot and qPCR were employed to evaluate the mRNA expression of senescence markers p21 and p53.ROS staining and JC-1 staining were applied to assess mitochondrial function in macrophages.The mRNA levels of Interleukin(IL)-6,IL-10,CD206,and inducible nitric oxide synthase(iNOS)were determined by qPCR analysis.Immunofluorescence was used to evaluate argi-nase(ARG1)and iNOS protein expressions for assessing the impact of drug-containing serum on macrophage polarization.qPCR analy-sis was conducted to measure osteocalcin(OCN),collagen type Ⅰ alpha 1(Col1a1),runt-related transcription factor 2(Runx2)mRNA levels as osteoblast-related markers;ALP staining along with alizarin red staining were performed to evaluate the effect of macrophage conditioned medium treated with drug-containing serum on bone marrow mesenchymal stromal cell(BMSC)osteogenic differentiation.C57BL/6J mice were randomly allocated into four groups:control group,model group,WTZR low-dose group,and WTZR high-dose group.The senile osteoporosis(SOP)mouse model was established by D-galactose.Micro-CT scanning analyzed fe-mur microstructure while HE staining detected pathological changes in femur bone tissue samples collected from each experimental con-dition.Furthermore,Western blot was used to detect the senescence-related molecules p21 and p53 and the osteogenesis-related mark-ers OCN and Runx2,qPCR analysis measured tibial expression levels of senescence-related molecules(p21,p53)as well as macro-phage polarisation-related molecules(IL-6,iNOS,CD206,and IL-10)to assess the effect of this compound on a mouse model simula-ting SOP.RESULTS Following intervention with serum containing WTZR,there was a significant decrease in the number of senes-cent positive cells compared to the model group.Additionally,there was a notable decrease in p21 and p53 mRNA and proteins expres-sion(P＜0.05,P＜0.01,P＜0.001).Furthermore,drug-containing WTZR effectively inhibited ROS production induced by H2 O2 and mitigated mitochondrial membrane potential reduction in macrophages(P＜0.05,P＜0.001).Treatment with drug-containing WTZR re-sulted in down-regulated mRNA expression of M1-related gene iNOS(P＜0.05)while up-regulating mRNA expression of M2-related genes CD163 and CD206(P＜0.05).The drug-containing WTZR significantly reduced fluorescence intensity for iNOS(P＜0.01)while increasing ARG1(P＜0.05)fluorescence intensity.Moreover,conditioned medium from macrophages treated with drug-containing ser-um increased ALP positive cell count(P＜0.01,P＜0.001),alizarin red positive area(P＜0.05),as well as Col1a1,Runx2 and OCN mRNA expression levels(P＜0.05,P＜0.01).The Tb.N,BMD,and BV/TV were significantly higher in the WTZR group compared to the model group(P＜0.05,P＜0.01,P＜0.001);meanwhile,Tb.Sp was notably lower than that observed in the model group(P＜0.05,P＜0.01);bone trabeculae were significantly improved,increased in number and widened.Additionally,the compound could significantly inhibit the D-galactose induced up-regulation of tibial senescence-related genes and proteins p21 and p53(P＜0.05,P＜0.001,P＜0.0001),promote the expression of osteogenesis-related markers OCN and Runx2 protein(P＜0.01,P＜0.0001),promote the down-regulation of M1 related genes IL-6 and iNOS(P＜0.05),and promote the expression of M2 related genes IL-10 and CD206(P＜0.05,P＜0.01).CONCLUSION Wenshen Tongluo Zhitong Recipe may play an anti-osteoporosis effect by inhibiting macrophage senescence and promoting the osteogenic differentiation of BMSC.

Objective:To explore the application value and operation skills of ultrasound-guided percutaneous thermal ablation assisted by artificial ascites or/and soft tissue edema in the treatment of special hepatic tumors located nearby the diaphragm, heart, stomach, gastrointestinal tract, gall bladder, kidney, and other organs.Methods:The clinical data of 132 patients with special-region hepatic tumors treated with ultrasound-guided percutaneous thermal ablation aided by artificial ascites and/or artificial soft tissue edema were retrospectively analyzed. Intraoperative contrast-enhanced ultrasound was used to guide ablation when necessary. During the operation, the ablation needle was lifted or pressed down, or the direction of the needle handle was changed to protect vital organs. The technical success rate of artificial ascites and/or soft tissue edema formation, the complete in activation rate of the tumor, and the complications were observed.Results:There were 74 patients (108 lesions) treated with radiofrequency ablation and 58 patients (82 lesions) treated with microwave ablation. Among them, 81 cases was successfully injected artificial abdominal ascites, with a water volume of (1 301±685) ml; artificial soft tissue edema was successfully formed for 19 patients, with a water volume of (534±258) ml. Both artificial ascites and artificial soft tissue edema were built for 30 patients. The success rate of this hydro-isolation technique was 98.5% (130/132). 129 patients successfully completed the treatment, and the complete inactivation rate of the tumor was 92.5% (172/186). The average postoperative hospital stay was three days. No patient had serious complications, such as surface tumor rupture, gastrointestinal injury, or diaphragm perforation.Conclusions:For hepatic tumors located adjacent to other organs such as the diaphragm, heart, gastrointestinal tract, gallbladder, and kidney, the application of artificial ascites and/or artificial soft tissue edema can reduce the damage to these organs, as well as reduce the possibility of tumor rupture and diaphragm perforation. These methods are safe and effective in ultrasound-guided percutaneous thermal ablation.

Objective To investigate the effects of remifentanil and dexmedetomidine controlled hypotension on coagulation function,cerebral oxygen metabolism and amino acid neurotransmitter levels in elderly patients undergoing orthopedic surgery.Methods The elderly patients who underwent lower extremity orthopedic surgery were divided into group A(given dexmedetomidine for hypotension),group B(given remifentanil for hypotension)and group C(given remifentanil combined with dexmedetomidine for hypotension)according to different anesthetic drugs.Systolic blood pressure(SBP),diastolic blood pressure(DBP)and heart rate(HR)were compared among the 3 groups.Cerebral oxygen metabolism[arterial oxygen content,(CaO2),oxygen saturation of internal jugular vein(SjvO2),oxygen content of internal jugular vein(CjvO2)],coagulation function[activated partial thromboplastin time(APTT),prothrombin time(PT),thrombin time(TT),plasma fibrinogen(FIB)],amino acid neurotransmitters[glutamic acid(Glu),aspartate(Asp),gamma-aminobutyric acid(GABA)]were compared,and the occurrence of adverse drug reactions during the trial were compared.Results At 12 h after anesthesia,the APTT of group A,group B and group C were(17.26±2.77),(17.37±2.92)and(31.11±4.74)s,respectively.GABA were(18.74±2.71),(19.22±2.60)and(23.37±2.59)mmol·L-1,respectively.3 min after withdrawal,CaO2 in group A,group B and group C were(139.31±9.03),(140.90±8.70)and(131.75±10.11)mL·L-1,respectively;SjvO2 were(63.59±2.23)％,(63.40±2.44)％and(68.82±3.36)％,respectively.The above indexes of group C were compared with those of group A and group B,and the differences were statistically significant(all P＜0.05).The incidence of adverse drug reactions in group A,B and C were 12.82％,27.50％and 7.32％,respectively.The incidence of adverse drug reactions in group C were lower than that in group A and group B(P＜0.05).Conclusion Remifentanil combined with dexmedetomidine for controlled hypotension in elderly orthopedic surgery has better blood pressure control effect,can improve postoperative coagulation function,maintain cerebral oxygen metabolism balance,reduce cognitive function injury and anesthesia adverse drug reactions.