ObjectiveTo elucidate the efficacy connotation of Shudi Qiangjin pills （SQP） against liver and kidney deficiency in steroid-induced osteonecrosis of femoral head （SONFH） from the perspective of the "disease-syndrome-formula" association and to clarify the underlying mechanisms based on in vivo and in vitro experiment validation. MethodsThe chemical components and the corresponding putative targets of SQP were collected from the Integrative Pharmacology-based Research Platform of Traditional Chinese Medicine （TCMIP） v2.0， the Encyclopedia of Traditional Chinese Medicine （ETCM） v2.0， and HERB databases. The SONFH-related genes were identified based on the differential expression profiles of peripheral blood of patients with SONFH compared to the healthy volunteers， and the disease phenotype-related targets were collected from the TCMIP v2.0 database. Then， the interaction network of "SONFH-related genes and candidate targets of SQP" was constructed based on "gene-gene interaction information"， and the major network targets were screened by calculating the topological characteristic values of the network followed by the functional mining according to the Kyoto Encyclopedia of Genes and Genomes （KEGG） database and the SoFDA database. After that， the SONFH rat model was prepared by lipopolysaccharide combined with methylprednisolone injection， and 2.5， 5， 7.5 g·kg^-1 SQP （once per day， equivalent to 1， 2， and 3 times the clinical equivalent dose， respectively） or 7.3×10^-3 g·kg^-1 of alendronate sodium （ALS， once per week， equivalent to the clinical equivalent dose） was given for 8 weeks. The effect characteristics of SQP and ALS in the treatment of SONFH were evaluated by micro-computed tomography scanning， hematoxylin and eosin staining， alkaline phosphatase （ALP） staining， immunohistochemical staining， enzyme-linked immunosorbent assay， and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling（TUNEL）staining， and a comparative efficacy analysis was conducted with ALS. In addition， SONFH cell models were prepared by dexamethasone stimulation of osteoblasts， and the intervention was carried out with the medicated serum of SQP at the aforementioned three doses. Cell counting kit-8， ALP staining， ALP activity assay， alizarin red staining， and flow cytometry were employed to investigate the regulatory effect of SQP on osteoblasts. The expression levels of osteogenesis-related proteins and key factors of the target signaling axis were detected by quantitative real-time polymerase chain reaction and Western blot. ResultsThe network analysis results demonstrated that the candidate targets of SQP primarily exerted their therapeutic effects through key signaling pathways， including phosphoinositide 3-kinase（PI3K）/protein kinase B（Akt）， lipid metabolism and atherosclerosis， prolactin， chemokines， and neurotrophic factors pathways. These pathways were significantly involved in critical biological processes such as muscle and bone metabolism and the regulation of the "neuro-endocrine-immune" network， thereby addressing both modern medical symptoms （e.g.， delayed skeletal maturation and recurrent fractures） and traditional Chinese medicine （TCM） symptoms （e.g.， fatigue， aversion to cold， cold limbs， and pain in the limbs and joints in patients with SONFH characterized by liver and kidney deficiency syndrome. Among these pathways， the PI3K/Akt signaling pathway exhibited the highest degree of enrichment. The in vivo experimental results demonstrated that starting from the 4^th week after modeling， the modeling group exhibited a significant reduction in body weight compared to the control group （P<0.05）. After six weeks of treatment， all dosage groups of SQP showed significantly higher body weights compared to the model group （P<0.01）. Compared with the normal group， the model group exhibited significant decreases in bone mineral density （BMD）， bone volume fraction （BV/TV）， trabecular number （Tb.N）， osteocalcin （OCN）， alkaline phosphatase （ALP） levels in femoral head tissue， and serum bone-specific alkaline phosphatase （BALP） （P<0.01）， along with significant increases in trabecular separation （Tb.Sp）， empty lacunae rate in tissue， and apoptosis rate （P<0.01）. In comparison to the model group， the SQP intervention groups showed significant improvements in BMD， BV/TV and Tb.N （P<0.01）， significant reductions in Tb.Sp， empty lacunae rate and apoptosis rate （P<0.05）， and significant increases in protein levels of OCN and ALP as well as BALP content （P<0.05）. The in vitro experimental results revealed that all dosage groups of SQP medicated serum showed no toxic effects on osteoblast. Compared with the normal group， the model group displayed significant suppression of osteoblast proliferation activity， ALP activity， and calcified nodule formation rate （P<0.01）， significant decreases in mRNA transcription levels of OCN and Runt-related transcription factor 2 （RUNX2） （P<0.01）， significant reductions in protein content of osteopontin （OPN）， typeⅠ collagen （ColⅠ）A1， B-cell lymphoma-2 （Bcl-2）， PI3K， and phosphorylated （p）-Akt （P<0.01）， and a significant increase in apoptosis rate （P<0.01）. Compared with the model group， the SQP medicated serum intervention groups exhibited significant increases in proliferation activity， ALP activity， calcified nodule formation rate， mRNA transcription levels of OCN and RUNX2， and protein content of OPN， ColⅠA1， Bcl-2， PI3K， and p-Akt （P<0.05）， along with a significant decrease in apoptosis rate （P<0.01）. ConclusionSQP can effectively reduce the disease severity of SONFH with liver and kidney deficiency syndrome and improve bone microstructure， with the therapeutic effects exhibiting a dose-dependent manner. The mechanism may be related to its regulation of key processes such as muscle and bone metabolism and the correction of imbalances in the "neuro-endocrine-immune" network， thereby promoting osteoblast differentiation and inhibiting osteoblast apoptosis. The PI3K/Akt signaling axis is likely one of the key pathways through which this formula exerts its effects.

BACKGROUND:The repair process of myocardial injury involves complex cellular and molecular mechanisms,especially mitochondrial calcium homeostasis,macrophage autophagy and pyroptosis pathways.Traditional Chinese medicine(TCM)has shown significant clinical efficacy in improving myocardial injury,but its mechanism of action needs to be thoroughly investigated. OBJECTIVE:To investigate the role of mitochondrial calcium homeostasis-mediated macrophage autophagy and pyroptosis pathways in myocardial injury,and to summarize the progress of TCM in this field. METHODS:A computerized search was performed for relevant literature from the database inception to March 2024 in the Web of Science,PubMed and CNKI.The search terms were"mitochondrial calcium homeostasis,macrophage autophagy,macrophage pyroptosis,traditional Chinese medicine,myocardial injury,myocardial injury reperfusion"in Chinese and English.Through literature review,we analyzed the relationship between mitochondrial calcium homeostasis and macrophage autophagy and pyroptosis,explored the mechanism of their roles in myocardial injury,and summarized the pathways of multi-targeted,multi-pathway effects of TCM. RESULTS AND CONCLUSION:The maintenance of mitochondrial calcium homeostasis has been found to be closely related to the normal function of cardiomyocytes.Macrophages can participate in the repair process of myocardial injury through autophagy and pyroptosis pathways.Autophagy contributes to cell clearance and regulation of inflammatory response,while pyroptosis affects myocardial repair by releasing inflammatory factors.TCM regulates mitochondrial calcium homeostasis and macrophage function through multiple mechanisms.For example,astragalosid regulates calcium homeostasis by lowering mitochondrial membrane potential and inhibiting cytochrome C,and epimedium glycoside plays a role in reducing β-amyloid deposition.In addition,herbal compounds and single drugs promote myocardial repair by activating or inhibiting specific signaling pathways,such as PI3K/AKT and nuclear factor-κB signaling pathways.Future studies should focus on the interactions between mitochondrial calcium homeostasis,autophagy and pyroptosis pathways,as well as how TCM can exert therapeutic effects through these pathways to provide new strategies and drugs for the treatment of myocardial injury.

Osteoporosis(OP)is a refractory metabolic bone disease,with decreased bone mineral mass,weakened bone strength,and systemic bone pain as typical clinical manifestations.Shenzhen Pingle Guo's Orthopedics,an important branch of the Pingle Guo's Orthopedics,has developed their distinct therapeutic approaches to the prevention and treatment of OP:the fifth-generation inheritor,Mr.Guo Chunyuan,advocated for the simultaneous regulation of qi and blood and formulated Shudi Zhuanggu Formula(composed of Rehmanniae Radix Praeparata,Codonopsis Radix,Atractylodis Macrocephalae Rhizoma,Poria,Angelicae Sinensis Radix,Paeoniae Radix Alba,Chuanxiong Rhizoma,Dipsaci Radix,and Achyranthis Bidentatae Radix);the sixth-generation inheritor,Professor Yang Zejin,emphasized zang-fu syndrome differentiation and established Yang's Guwei Formula,which simultaneously tonifies the liver,spleen,and kidney,and simultaneously treats deficiency and blood stasis(composed of Astragali Radix,Rehmanniae Radix Praeparata,Achyranthis Bidentatae Radix,Epimedii Folium,Cistanches Herba,Cuscutae Semen,Drynariae Rhizoma,Angelicae Sinensis Radix,Salviae Miltiorrhizae Radix et Rhizoma,Notoginseng Radix et Rhizoma,Corydalis Rhizoma,and Paeoniae Radix Alba);the seventh-generation inheritor,Professor Gong Chunzhu,proposed a three-stage clinical treatment strategy and stressed the principle of reinforcing acquired foundation of life(i.e.,reinforcing spleen and stomach),and formulated the modified Shudi Zhuanggu Formula with Lingnan characteristics(composed of Rehmanniae Radix Praeparata,Corni Fructus,Dioscoreae Rhizoma,Alismatis Rhizoma,Poria,Moutan Cortex,Astragali Radix,Dipsaci Radix,Cyathulae Radix,Acanthopanacis Cortex,Atractylodis Macrocephalae Rhizoma,Codonopsis Radix,and Chaenomelis Fructus).During the evolution,Shenzhen Pingle Orthopedic Hospital has continuously integrated modern medical achievements,passed down and enriched the clinical experience,and then the theoretical framework of traditional Chinese medicine in the prevention and treatment of OP has been developed.

Osteoporotic proximal humeral fracture (OPHF) is one of the common osteoporotic fractures in the aged, with an incidence only lower than vertebral compression fracture, hip fracture, and distal radius fracture. OPHF, secondary to osteoporosis and characterized by poor bone quality, comminuted fracture pattern, slow healing, and severely impaired shoulder joint function, poses a big challenge to the current clinical diagnosis and treatment. In the field of diagnosis, treatment, and rehabilitation of OPHF, traditional Chinese and Western medicine have accumulated rich experience and evidence from evidence-based medicine and achieved favorable outcomes. However, there is still a lack of guidance from a relevant consensus as to how to integrate the advantages of the two medical systems and achieve the integrated diagnosis and treatment. To promote the diagnosis and treatment of OPHF with integrated traditional Chinese and Western medicine, relevant experts from Orthopedic Expert Committee of Geriatric Branch of Chinese Association of Gerontology and Geriatrics, Youth Osteoporosis Group of Orthopedic Branch of Chinese Medical Association, Osteoporosis Group of Orthopedic Surgeon Branch of Chinese Medical Doctor Association, and Osteoporosis Committee of Shanghai Association of Integrated Traditional Chinese and Western Medicine have been organized to formulate Expert consensus on the diagnosis and treatment of osteoporotic proximal humeral fracture with integrated traditional Chinese and Western medicine ( version 2024) by searching related literatures and based on the evidences from evidence-based medicine. This consensus consists of 13 recommendations about the diagnosis, treatment and rehabilitation of OPHF with integrated traditional Chinese medicine and Western medicine, aimed at standardizing, systematizing, and personalizing the diagnosis and treatment of OPHF with integrated traditional Chinse and Western medicine to improve the patients ′ function.

Laparoscopic distal pancreatectomy is the conventional treatment for tumors of the pancreatic body or tail.And laparoscopic spleen-preserving distal pancreatectomy has been emphasized because it can preserve the spleen's function and lower the complications following splenectomy.However,the occult onset and complex anatomical location of pancreatic tumors pose a challenge to their diagnosis and spleen-preserving distal pancreatectomy.In recent years,our team has accumulated rich experience in the diagnosis and treatment of pancreatic tumors,and innovatively proposed the"SELECT"concept(S-Single-Operator Cholangiopancreatoscopy,E-ERCP,L-Laparoscopy,E-Endoscopic ultrasound,C-Choledochoscopy/Confocal laser endomicroscopy,T-Traditional Chinese medicine)for diagnosis and treatment.Based on the various characteristics of pancreatic tumors,various endoscopic and laparoscopic techniques are applied,and an optimal combination of various minimally invasive methods is selected.Fully applying the SELECT concept to laparoscopic spleen-preserving distal pancreatectomy is conducive to accurate preoperative diagnosis,accurate intraoperative resection,prediction and treatment of postoperative complications,and one-stop diagnosis and treatment of pancreatic tumors,maximizing patient benefits.

The eutR gene deletion mutant of Salmonella enteritidis was successfully constructed by homologous recombination.Through the study of its biochemical characteristics,motility,resist-ance to stress in vitro and survival ability in RAW 264.7 cells,it was found that the biochemical characteristics and motility of the eutR gene deletion mutant of Salmonella enteritidis had no sig-nificant change compared with the wild type of Salmonella enteritidis.The ability of eutR gene de-letion strain of Salmonella enteritidis to resist acid,alkali and oxidation was significantly reduced,while the ability to resist heat was not significantly changed;the survival ability of eutR gene dele-tion strain in RAW 264.7 cells was significantly reduced compared with the wild type.In order to further analyze the effect of eutR gene on the expression of virulence factors of Salmonella enterit-idis,the relative expression levels of invH,ssav,ssrA,xthA,orf245,sodC,lrp,mrr1 and hflk virulence genes of the deletion strain and the wild strain were detected by SYBR Green PCR.It was found that the expression of the virulence factors mentioned above in the eutR gene deletion strain of Salmonella enteritidis was significantly down-regulated compared with that in the wild-type strain.The LD50 of the eutR gene-deleted strain of Salmonella enteritidis was determined by ani-mal experiments,and the results showed that the LD50 of the eutR gene-deleted strain was higher than that of the wild-type strain,indicating that the eutR gene could affect the virulence of Salmonella.This study clarified the effect of eutR gene on the survival ability,some biological characteristics and virulence of Salmonella enteritidis in macrophages,and provided a new gene knockout target for the development of attenuated Salmonella enteritidis genetic engineering vac-cine.

Objective:To predict the docetaxel-sensitive prostate cancer based on metabolic subtypes and biomarkers.Methods:Gene expression profiles and clinical data of prostate cancer patients were downloaded from the cancer genome atlas (TCGA) and GEO databases. Single-factor Cox regression analysis was used to screen for metabolic-related genes in prostate cancer, and a prognostic model was constructed using the glmnet package. Metabolic subtypes were classified using the ConsensusClusterPlus package. Weighted gene co-expression network was used to analyze the biomarkers of docetaxel-sensitive prostate cancer. Ribonucleotide reductase M2 ( RRM2) gene was silenced by transfection of blank vector and short hairpin RNA (shRNA) of RRM2 to inhibit its expression. The relative expression level of RRM2 protein in docetaxel-resistant PC-3-DR cells was detected by Western blotting. The effects of RRM2 on the number of colonies and the number of cells migrating to the lower chamber of PC-3-DR cells were determined by colony formation assay and cell migration assay. Results:A total of 8 genes were screened, including synaptojanin 1 ( SYNJ1), RRM2, macrophage migration inhibitory factor ( MIF), fucose-1-phosphate guanyltransferase ( FPGT), arginase 1 ( ARG1), adenosylmethionine decarboxylase 1 ( AMD1), aldo-keto reductase family 1, member B10 ( AKR1B10), and acyl-CoA synthetase short chain family member 2 ( ACSS2). A model for predicting the prognosis of prostate cancer patients was constructed, and the area under the curve for predicting 3-year disease-free survival of prostate cancer was 0.70. Three different metabolic subtypes were identified. The disease-free survival of C3 subtype was shorter ( P=0.018), and the half maximal inhibitory concentration (IC 50) of docetaxel in the C3 subtype was lower than that in the C1 and C2 subtypes (all P<0.01). The genes and biomarkers associated with docetaxel resistance were acyl-CoA oxidase 1 ( ACOX1), isocitrate dehydrogenase 1 ( IDH1), glutathione S-transferase kappa 1 ( GSTK1), sterol carrier protein 2 ( SCP2), and solute carrier family 27 member 2 ( SLC27A2). In PC-3-DR cells, the relative expression levels of RRM2 and Ki67 proteins in the transfection group (1.77±0.15, 0.52±0.08) were lower than those in the control group (3.10±0.26, 1.18±0.13), and the differences were statistically significant (all P<0.05). The number of colonies and the number of cells migrating to the lower chamber in the transfection group [(56.00±3.61, 81.67±15.82) unit] were lower than those in the control group [(151.70±7.37, 320.00±35.37) unit], and the differences were statistically significant (all P<0.05). Conclusions:The multi-gene-based prognostic model can successfully predict disease-free survival of prostate cancer patients. Advanced prostate cancer patients with C3 subtype based on metabolic genes are suitable for docetaxel-based chemotherapy.

Cholelithiasis is a common and frequent disease of the digestive system, and its incidence rate tends to increase with the improvement of living standards. Patients suffering from both gallbladder stones and common bile duct stones account for 5%-15%. Choledocholithiasis can cause a series of serious complications such as acute cholangitis and biliary pancreatitis. Choledocholithotomy is the main method for the treatment of choledocholithiasis, but there is still a high recurrence rate after surgery. The recurrence of choledocholithiasis seriously affects the life of patients and increases their economic burden. With reference to the latest published clinical studies, this article summarizes the influencing factors for the recurrence of choledocholithiasis from the aspects of anatomical factors, stone-related factors, biliary factors, and surgical factors, so as to provide a reference for the treatment of choledocholithiasis and the prevention of its recurrence.

ObjectiveTo investigate the effect of Qingre Lidan granules in preventing the recurrence of choledocholithiasis after laparoscopy combined with choledochoscopy through a retrospective cohort study. MethodsA total of 337 inpatients with choledocholithiasis （including those with cholecystolithiasis at the same time） who underwent laparoscopy combined with choledochoscopic lithotomy in The First Affiliated Hospital of Dalian Medical University from January 1， 2010 to December 31， 2020 were enrolled， and related clinical data were collected. According to the follow－up results， the patients were divided into exposure group （conventional treatment+Qingre Lidan granules） with 225 patients and non－exposure group （conventional treatment） with 112 patients. The recurrence of choledocholithiasis and the administration of Qingre Lidan granules were recorded in detail for both groups. The recurrence rate of choledocholithiasis and the time to recurrence were observed for both groups， and the risk factors for the recurrence of choledocholithiasis were analyzed. The independent－samples t test was used for comparison of normally distributed continuous data between two groups， and the Mann－Whitney U test was used for comparison of non－normally distributed continuous data between two groups； the chi－square test or the Fisher’s exact test was used for comparison of categorical data between two groups. The Kaplan－Meier curve was used to estimate the cumulative probability of choledocholithiasis recurrence in the two groups， and the Log－rank test was used for comparison between two groups. ResultsA total of 26 patients experienced the recurrence of choledocholithiasis after laparoscopy combined with choledochoscopy， with 12 patients （5.33%） in the exposure group and 14 （12.5%） in the non－exposure group， and the exposure group had a significantly lower recurrence rate than the non－exposure group （χ²=5.394， P=0.020）. The exposure group had a significantly longer mean time to the recurrence of choledocholithiasis than the non－exposure group （40.1±26.7 months vs 19.2±13.5 months， t=2.383， P=0.017）. The Kaplan－Meier curve analysis showed that the non－exposure group had a significantly higher cumulative recurrence rate than the exposure group in different periods of time （P<0.05）. The multivariate logistic regression analysis showed that common bile duct diameter ≥14 mm （odds ratio 〔OR〕=2.935， P=0.031） and multiple calculi （OR=2.911， P=0.029） were independent risk factors for the recurrence of choledocholithiasis after laparoscopy combined with choledochoscopic lithotomy. ConclusionQingre Lidan granules can effectively reduce the recurrence rate of choledocholithiasis and prolong the time to the recurrence of choledocholithiasis after laparoscopy combined with choledochoscopy and has a certain clinical effect in preventing the recurrence of choledocholithiasis after surgery.

Six new abietane diterpenoids (1-6) and five undescribed iridoids (7-11) have been isolated from the aerial parts of Caryopteris mongolica. The intricate structural characterization of these compounds was meticulously undertaken using an array of advanced spectroscopic techniques. This process was further enhanced by the application of DP4+ probability analyses and electronic circular dichroism (ECD) calculations. Following isolation and structural elucidation, the cytotoxicity of these compounds was evaluated. Among them, compound 3 stood out, displaying significant cytotoxic activity against HeLa cells with an IC₅₀ value of 7.83 ± 1.28 μmol·L^-1. Additionally, compounds 1, 2, 4, 9, and 10 manifested moderate cytotoxic effects on specific cell lines, with IC₅₀ values ranging from 11.7 to 20.9 μmol·L^-1.
Humans ; Abietanes/chemistry* ; HeLa Cells ; Lamiaceae/chemistry* ; Circular Dichroism ; Diterpenes/chemistry* ; Molecular Structure