ObjectiveTo investigate the effects of modified Buyang Huanwu Tang on cerebral ischemia-reperfusion injury （CI/RI） in mice via the PTEN-induced putative kinase 1/E3 ubiquitin ligase （PINK1/Parkin） signaling pathway-mediated mitophagy， and to explore the underlying mechanism by which modified Buyang Huanwu Tang improves CI/RI. MethodsSeventy-two male C57BL/6J mice were randomly divided into six groups （n = 12 per group）： Sham-operated group， middle cerebral artery occlusion/reperfusion （MCAO/R） model group， low-， medium-， and high-dose modified Buyang Huanwu Tang groups （8.84， 17.68， 35.36 g·kg^-1·d^-1）， and an aspirin group （13.00 mg·kg^-1·d^-1）. Neurological deficit scores were assessed using the Zea-Longa method. Cerebral infarct volume ratio was measured by 2，3，5-triphenyltetrazolium chloride （TTC） staining. Histopathological changes and neuronal injury in brain tissues were observed using hematoxylin-eosin （HE） staining and Nissl staining. Apoptosis was detected by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling （TUNEL） assay. Mitochondrial ultrastructure in brain tissue was observed by transmission electron microscopy （TEM）. Serum levels of superoxide dismutase （SOD） and malondialdehyde （MDA） were determined by enzyme-linked immunosorbent assay （ELISA）. The mRNA and protein expression levels of PINK1， Parkin， microtubule-associated protein 1 light chain 3B （LC3B， LC3Ⅱ/Ⅰ）， and p62 in brain tissues were detected by real-time quantitative reverse transcription PCR （Real-time PCR） and Western blot， respectively. ResultsCompared with the sham-operated group， the MCAO/R model group showed significantly increased neurological deficit scores and cerebral infarct volume ratios （P<0.01）. Severe cortical injury on the infarct side was observed， characterized by decreased neuronal density， cytoplasmic vacuolation， nuclear pyknosis， a marked reduction in Nissl bodies， dissolution of Nissl bodies in the cytoplasm of some pyramidal neurons， and blurred cellular boundaries. The number of TUNEL-positive cells increased significantly （P<0.01）. Mitochondria exhibited cristae membrane rupture and matrix vacuolation， with rupture of the outer mitochondrial membrane and formation of autophagosomes， the number of which increased significantly. Serum SOD activity decreased significantly （P<0.01）， while MDA content increased significantly （P<0.01）. In infarcted brain tissues of model mice， the relative mRNA expression and protein levels of PINK1， Parkin and LC3B were significantly increased （P<0.05， P<0.01）， whereas p62 mRNA and protein expression were significantly decreased （P<0.05， P<0.01）， showing statistical significance. Compared with the model group， all treatment groups showed significantly decreased neurological deficit scores and cerebral infarct volume ratios （P<0.01）. Neuronal density increased significantly， cytoplasmic vacuolation was alleviated， nuclear morphology tended to be more regular and clearer， Nissl body density increased significantly with reduced dissolution and improved contour clarity. The mitochondrial cristae structure was partially restored， with some mitochondria showing autophagosome encapsulation， and the degree of mitochondrial damage was alleviated. Serum SOD activity increased significantly （P<0.01）， while MDA content decreased significantly. The mRNA and protein expression levels of PINK1， Parkin， and LC3Ⅱ/Ⅰ were significantly increased （P<0.05， P<0.01）， while p62 mRNA and protein expression in the low- and medium-dose modified Buyang Huanwu Tang groups were significantly decreased （P<0.05， P<0.01）， showing statistical significance. ConclusionModified Buyang Huanwu Tang can upregulate the protein expression levels of PINK1， Parkin， and LC3Ⅱ/Ⅰ and downregulate p62 protein expression， suggesting that it may improve CI/RI by regulating the expression of proteins related to the PINK1/Parkin signaling pathway. Regulation of the mitophagy pathway may be one of the mechanisms by which modified Buyang Huanwu Tang alleviates CI/RI in mice.

OBJECTIVE To explore the mecha nism by which Liuwei dihuang pill promotes tendon-bone healing by regulating the interaction between bone marrow mesenchymal stem cells （BMSCs） and macrophages through Wnt/ β -catenin pathway. METHODS BMSCs were co-cultured with macrophages at a ratio of 1∶4 and divided into control group， 10% drug-containing serum group， 20% drug-containing serum group， Wnt/ β -catenin pathway inhibitor Dickkopf-related protein 1 （DKK-1） group， and 20% drug-containing serum+DKK-1 group. After 48 hours of cell co-culture and 14 days of osteogenic induction， the CD86 and CD206 positive cell rates in macrophages， the proportion of calcium nodule positive staining area in BMSCs， the levels of osteocalcin （OCN） and oncostatin M （OSM） and alkaline phosphatase （ALP） activity in cell supernatant， as well as the mRNA and protein expression levels of OCN， Runt-related transcription factor 2 （RUNX2）， OSM， low-density lipoprotein receptor-related protein 5 （LRP5）， β -catenin in cells were detected. Pearson correlation analysis was performed to assess the correlation between LRP5 and β -catenin protein expression with OCN， RUNX2， OSM protein expression， and CD206 positive cell rate， respectively. RESULTS Compared with the control group， the CD86 positive cell rates in the 10% drug-containing serum group and the 20% drug-containing serum group were significantly reduced， while the CD206 positive cell rate， proportion of calcium nodule positive staining area， OCN level， OSM level， ALP activity， and mRNA and protein expression levels of OCN， RUNX2， OSM， LRP5， β -catenin were significantly increased （ P ＜0.05）. Compared with the 20% drug-containing serum group， the changes in the above indicators in the 20% drug-containing serum+DKK-1 group were significantly reversed （ P ＜0.05）. The protein expression of LRP5 and β -catenin was positively correlated with the pro tein expression of OCN， RUNX2， OSM， and CD206 positive cell rate. CONCLUSIONS Liuwei dihuang pill can activate the Wnt/ β -catenin pathway， induce M2 polarization of macrophages and secretion of OSM， promote osteogenic differentiation and matrix mineralization of BMSCs， and synergistically promote tendon-bone healing.

OBJECTIVE To explore the mecha nism by which Liuwei dihuang pill promotes tendon-bone healing by regulating the interaction between bone marrow mesenchymal stem cells （BMSCs） and macrophages through Wnt/ β -catenin pathway. METHODS BMSCs were co-cultured with macrophages at a ratio of 1∶4 and divided into control group， 10% drug-containing serum group， 20% drug-containing serum group， Wnt/ β -catenin pathway inhibitor Dickkopf-related protein 1 （DKK-1） group， and 20% drug-containing serum+DKK-1 group. After 48 hours of cell co-culture and 14 days of osteogenic induction， the CD86 and CD206 positive cell rates in macrophages， the proportion of calcium nodule positive staining area in BMSCs， the levels of osteocalcin （OCN） and oncostatin M （OSM） and alkaline phosphatase （ALP） activity in cell supernatant， as well as the mRNA and protein expression levels of OCN， Runt-related transcription factor 2 （RUNX2）， OSM， low-density lipoprotein receptor-related protein 5 （LRP5）， β -catenin in cells were detected. Pearson correlation analysis was performed to assess the correlation between LRP5 and β -catenin protein expression with OCN， RUNX2， OSM protein expression， and CD206 positive cell rate， respectively. RESULTS Compared with the control group， the CD86 positive cell rates in the 10% drug-containing serum group and the 20% drug-containing serum group were significantly reduced， while the CD206 positive cell rate， proportion of calcium nodule positive staining area， OCN level， OSM level， ALP activity， and mRNA and protein expression levels of OCN， RUNX2， OSM， LRP5， β -catenin were significantly increased （ P ＜0.05）. Compared with the 20% drug-containing serum group， the changes in the above indicators in the 20% drug-containing serum+DKK-1 group were significantly reversed （ P ＜0.05）. The protein expression of LRP5 and β -catenin was positively correlated with the pro tein expression of OCN， RUNX2， OSM， and CD206 positive cell rate. CONCLUSIONS Liuwei dihuang pill can activate the Wnt/ β -catenin pathway， induce M2 polarization of macrophages and secretion of OSM， promote osteogenic differentiation and matrix mineralization of BMSCs， and synergistically promote tendon-bone healing.

Objective:To investigate the effects of Porphyromonas gingivalis derived outer membrane vesicles (Pg OMV) on osteoclast differentiation of macrophages and its underlying mechanisms. Methods:The morphology and the size distribution of Pg OMV were analyzed by transmission electron microscopy and nanoparticle tracing analysis, respectively. The osteoclast precursors were treated with 1, 3 and 10 mg/L Pg OMV (1, 3 and 10 mg/L OMV treatment group) or phosphate buffer solution (PBS)(control group). The formation of osteoclasts was analyzed by tartrate-resistant acid phosphase (TRAP) staining and F-actin staining and real-time quantitative PCR (RT-qPCR) were used to detect the expression of Fos and matrix metallopeptidase 9 (MMP9). Polymyxin B (PMB) was used to block lipopolysaccharide (LPS) and then Pg OMV was used to treat osteoclast precursor (PMB-OMV treatment group), and OMV treatment group was used as control. TRAP and F-actin staining were used to observe the formation of osteoclasts and actin rings. The effect of Pg OMV on the expression of Toll-like receptor (TLR) 2 and TLR4 in preosteoclasts was detected by Western blotting. The osteoclast precursors were pretreated with 10, 50, 100 and 200 μmol/L C29, an inhibitor of TLR2, and then treated with Pg OMV(OMV+10, 50, 100 and 200 μmol/L C29 treatment group) and OMV treatment group without C29 pretreatment was control. TRAP and F-actin staining were used to observe the formation of osteoclasts and actin rings. The osteoclast precursor cells were treated with OMV (OMV treatment group) and OMV incubated with PMB (PMB-OMV treatment group) and the expression of TLR2 in osteoclast precursor was detected by Western blotting.Results:Pg OMV showed classical vesicular structures, and the average particle size of Pg OMV were 179.2 nm. A large number of actin rings were observed in the 3 and 10 mg/L OMV treatment groups. The percentages of TRAP-positive osteoclast area in 3 mg/L OMV treatment group [(22.6±2.1)%] and 10 mg/L OMV treatment group [(32.0±2.3)%] were significantly increased compared with control group [(4.9±0.5)%] ( P<0.001). Compared with the control group (1.000±0.029), the mRNA relative expression of Fos in 3 mg/L OMV treatment group (1.491±0.114) and 10 mg/L OMV treatment group (1.726±0.254) was significantly increased ( P=0.013, P=0.001). Compared with the control group (1.007±0.148), the mRNA relative expression of MMP9 in the group of 10 mg/L OMV (2.232±0.097) was significantly increased ( P<0.001). Actin ring formation was less in PMB-OMV treatment groups than in OMV treatment groups. The proportion of TRAP-positive osteoclasts area [(14.8±3.8)%] in PMB-OMV treatment group was significantly lower than OMV treatment group [(31.5±6.7) %] ( P=0.004). The relative expression of TLR2 in OMV treatment group (1.359±0.134) was significantly higher than that in the control group (1.000±0.000) ( t=4.62, P=0.044). Compared with the OMV treatment group [(29.4±1.7)%], 50, 100 and 200 μmol/L C29 significantly decreased the formation of osteoclasts [(24.0±1.7)%, (18.5±2.1)%, (9.1±1.3) %] ( P=0.026, P<0.001, P<0.001). TLR2 protein expression in PMB-OMV group (0.780±0.046) was significantly lower than that in OMV group (1.000±0.000)( t=8.32, P=0.001). Conclusions:Pg OMV can promote osteoclast differentiation by carrying LPS, TLR2 plays an important role in Pg OMV mediated osteoclast differentiation.

Periarticular fracture of the shoulder is a common type of fractures in the elderly. Postoperative adverse events such as internal fixation failure, humeral head ischemic necrosis and upper limb dysfunction occur frequently, which seriously endangers the exercise and health of the elderly. Compared with the fracture with normal bone mass, the osteoporotic periarticular fracture of the shoulder is complicated with slow healing and poor rehabilitation, so the clinical management becomes more difficult. At present, there is no targeted guideline or consensus for this type of fracture in China. In such context, experts from Youth Osteoporosis Group of Chinese Orthopedic Association, Orthopedic Expert Committee of Geriatrics Branch of Chinese Association of Gerontology and Geriatrics, Osteoporosis Group of Youth Committee of Chinese Association of Orthopedic Surgeons and Osteoporosis Committee of Shanghai Association of Chinese Integrative Medicine developed the Chinese expert consensus on the diagnosis and treatment of osteoporotic periarticular fracture of the shoulder in the elderly ( version 2023). Nine recommendations were put forward from the aspects of diagnosis, treatment strategies and rehabilitation of osteoporotic periarticular fracture of the shoulder, hoping to promote the standardized, systematic and personalized diagnosis and treatment concept and improve functional outcomes and quality of life in elderly patients with osteoporotic periarticular fracture of the shoulder.

Osteoporotic thoracolumbar fracture in the elderly will seriously reduce their quality of life and life expectancy. For osteoporotic thoracolumbar fracture in the elderly, spinal reconstruction is necessary, which should comprehensively consider factors such as the physical condition, fracture type, clinical characteristics and osteoporosis degree. While there lacks relevant clinical norms or guidelines on selection of spinal reconstruction strategies. In order to standardize the concept of spinal reconstruction for osteoporotic thoracolumbar fracture in the elderly, based on the principles of scientificity, practicality and progressiveness, the authors formulated the Clinical guideline for spinal reconstruction of osteoporotic thoracolumbar fracture in elderly patients ( version 2022), in which suggestions based on evidence of evidence-based medicine were put forward upon 10 important issues related to the fracture classification, non-operative treatment strategies and surgical treatment strategies in spinal reconstruction after osteoporosis thoracolumbar fracture in the elderly, hoping to provide a reference for clinical treatment.

Citri Reticulatae Pericarpium is a commonly used traditional Chinese medicine in China. By referring to herbal monographs and related research documents， and comparing all editions of Chinese Pharmacopoeia and local processing specifications， the processing history， modern processing specifications， study on chemical constituents and pharmacological effects before and after processing of Citri Reticulatae Pericarpium were summarized. It was found that the processing methods of Citri Reticulatae Pericarpium in the past dynasties were mainly cleansing， cutting and frying. The processing methods of Citri Reticulatae Pericarpium included in all editions of Chinese Pharmacopoeia were all cleansing and cutting. In modern local processing specifications， there were mainly processing methods such as frying， steaming and carbonizing. The components of Citri Reticulatae Pericarpium were mainly volatile oil and flavonoids. After processing， the total amount of volatile oil generally decreased， and the contents and compositions of volatile oil and flavonoids also changed. It may be the main reason for the difference of efficacy before and after processing. At present， the optimization of processing technology of Citri Reticulatae Pericarpium mainly focuses on steaming， processing with vinegar and baking. Pharmacological research on Citri Reticulatae Pericarpium mainly focuses on reducing blood lipid， relieving cough， relieving asthma and resolving phlegm， and inhibiting pulmonary fibrosis. The current research on the processing methods of Citri Reticulatae Pericarpium is not in-depth enough， the material basis of many processing methods has not been clarified， and the research on the efficacy before and after processing is not in-depth enough. Further research is needed to clarify the material basis and mechanism after the processing of Citri Reticulatae Pericarpium， so as to standardize the processing method and establish specific quality standards.

Glycyrrizae Radix et Rhizoma has high medicinal value and is widely used in compatibility. It is used most frequently in the compatibility of Chinese medicine prescriptions，and is known as ''Guolao''（national medicine） and "master of all medicines". The characteristic active ingredients are mainly liquitin，glycyrrizic acid，glycyrrizin，and licochalcone. In different compatibilities，based on traditional and modern pharmacological theories，the corresponding effect of Glycyrrizae Radix et Rhizoma are brought into play through different mechanisms. Based on the traditional pharmacology of Glycyrrizae Radix et Rhizoma for tonifying spleen，replenishing Qi，clearing heat，removing toxin，dispelling phlegm，relieving cough and pain，and harmonizing various medicines，this paper used herbal authentication to analyze its compatibility application and mechanism. It was found that Glycyrrizae Radix et Rhizoma played corresponding effect in compatibilities through "tonification"，"harmonization"，and "regulation". For example，Glycyrrizae Radix et Rhizoma was combined with tonics including Ginseng Radix et Rhizoma and Atractylodis Macrocephalae Rhizoma to tonify the five Zang-organs through its strong tonifying effect，combined with Paeoniae Radix Alba and Aconiti Lateralis Radix Praeparata to relieve emergencies and pains through harmonizing medicine power and properties，and combined with Rhei Radix et Rhizoma and Natrii Sulfas to reduce medicine intensity through regulating medicine properties and body characteristics. The application law and mechanism of the modern pharmacological compatibility of Glycyrrizae Radix et Rhizoma were analyzed by data mining and network pharmacology. It was found that the modern clinical formula was often compatible with Glycyrrizae Radix et Rhizoma for anti-inflammation，cardiovascular and cerebrovascular protection，anti-virus，and anti-tumor，Ephedrae Herba and Scutellariae Radix for anti-inflammation，Bambusae Caulis in Taenias，Salviae Miltiorrhizae Radix et Rhizoma，and Aurantii Fructus Immaturus for cardiovascular and cerebrovascular protection，and Ophiopogonis Radix and Chuanxiong Rhizoma for nerves protection. Meanwhile，the important targets of the characteristic ingredients were protein kinase B1 （Akt1），interleukin-6 （IL-6），tumor necrosis factor （TNF），and epidermal growth factor receptor （EGFR）. The important characteristic pathways such as tyrosine kinase inhibitor resistance pathway and cyclic guanosine monophosphate （cGMP）/protein kinase G （PKG） signal pathway played the role of cardiovascular and cerebrovascular protection，and proteoglycan pathway in cancer played a neuroprotective role. This study is expected to provide references for the rational compatibility and application of Glycyrrizae Radix et Rhizoma，as well as the compatibility application of Chinese medicine prescriptions.

Objective:To systematically evaluate the relationship between growth and thyroid volume (Tvol).Methods:Chinese and English papers were searched in CNKI, Wanfang Data, VIP Database, PubMed, EMbase, Springerlink, Medline database, articles on the correlation between Tvol and growth in children published from the establishment of these databases to October 2021 were collected. Meta-analysis was conducted with R language 4.0. I2 and Q test were used for heterogeneity test. According to the heterogeneity test results, the fixed effect model or random effect model was selected, and sensitivity analysis was conducted. Egger's method was used to test publication bias. Results:A total of 17 papers were incorporated in this study, including 11 Chinese papers and 6 English papers. The correlation between body surface area (BSA) and Tvol was the strongest[estimated effect value ( COR) = 0.44, 95% confidence interval ( CI): 0.39 - 0.50], followed by weight ( COR = 0.39), height ( COR = 0.37) and age ( COR = 0.29). Sensitivity analysis showed that the estimated effects COR were all within 95% CI of the total effects after deleting any paper, which indicated that the results of Meta-analysis were reliable. Egger's method result showed P > 0.05, indicating that there was no obvious publication bias in this study. Conclusion:Age, height, weight and BSA all have effects on Tvol, among which BSA has the greatest effect.

Zedoary tumeric (Curcumae Rhizoma, Ezhu in Chinese) has a long history of application and has great potential in the treatment of liver cancer. The antiliver cancer effect of zedoary tumeric depends on the combined action of multiple pharmacodynamic substances. In order to clarify the specific mechanism of zedoary tumeric against liver cancer, this paper first analyzes the mechanism of its single pharmacodynamic substance against liver cancer, and then verifies the joint anti liver cancer mechanism of its “pharmacodynamic group”. By searching the research on the antihepatoma effect of active components of zedoary tumeric in recent years, we found that pharmacodynamic substances, including curcumol, zedoarondiol, curcumenol, curzerenone, curdione, curcumin, germacrone, β-elemene, can act on multi-target and multi-channel to play an antihepatoma role. For example, curcumin can regulate miR, GLO1, CD133, VEGF, YAP, LIN28B, GPR81, HCAR-1, P53 and PI3K/Akt/mTOR, HSP70/TLR4 and NF-κB. Wnt/TGF/EMT, Nrf2/Keap1, JAK/STAT and other pathways play an antihepatoma role. Network pharmacological analysis showed that the core targets of the “pharmacodynamic group” for anti-life cancer are AKT1, EGFR, MAPK8, etc, and the core pathways are neuroactive live receiver interaction, nitrogen metabolism, HIF-1 signaling pathway, etc. At the same time, by comparing and analyzing the relationship between the specific mechanisms of pharmacodynamic substance and “pharmacodynamic group”, it is found that they have great reference significance in target, pathway, biological function, determination of core pharmacodynamic components, formation of core target protein interaction, in-depth research of single pharmacodynamic substance, increasing curative effect and so on. By analyzing the internal mechanism of zedoary tumeric pharmacodynamic substance and “pharmacodynamic group” in the treatment of liver cancer, this paper intends to provide some ideas and references for the deeper pharmacological research of zedoary tumeric and the relationship between pharmacodynamic substance and “pharmacodynamic group”.