ObjectiveTo investigate the mechanisms by which Huanglian Jiedutang （HLJDT） modulates microglial （MG） phenotypes through the sialic acid-binding Ig-like lectin 2 （SIGLEC2/CD22）/Src-homology-2-domain-containing protein tyrosine phosphatase-1 （SHP-1）/phosphorylated protein kinase B （p-Akt） signaling pathway， thereby promoting myelin repair and alleviating agitation-like behaviors in vascular dementia （VAD）. MethodsSixty C57BL/6J mice were randomly assigned to a sham （normal） group， model group， HLJDT low-， medium-， and high-dose groups （2.5， 5， and 10 g·kg^-1·d^-1）， and a risperidone group （2 mg·kg^-1·d^-1）， with 10 mice per group. VAD was induced by bilateral common carotid artery stenosis （BCAS）. From day 42， mice received drug interventions for 2 weeks. Agitation-like behaviors were assessed using the resident-intruder test. After behavioral testing， ventrolateral part of the ventromedial hypothalamus （VMHvl） tissues were collected. Western blot was used to measure protein levels of myelin oligodendrocyte glycoprotein （MOG）， myelin basic protein （MBP）， proteolipid protein （PLP）， inducible nitric oxide synthase （iNOS）， arginase-1 （Arg1）， CD86， CD206， and CD22， SHP-1， and p-Akt. Immunofluorescence was used to evaluate myelin-associated glycoprotein （MAG） intensity and the proportion of iNOS⁺/ionized calcium-binding adapter molecule 1 （Iba1）⁺ cells. ELISA was used to detect tumor necrosis factor-α （TNF-α）， interleukin （IL）-6， and IL-1β. ResultsCompared with the normal group， the model group exhibited markedly increased biting and aggressive behaviors and shortened attack latency （P<0.01）. MOG， MBP， and PLP protein levels and MAG fluorescence intensity were significantly reduced （P<0.05， P<0.01）. INOS and CD86 expression and TNF-α， IL-6， and IL-1β levels were significantly elevated （P<0.01）. CD22 and SHP-1 expression increased significantly （P<0.01）， whereas p-Akt expression decreased （P<0.01）. Compared with the model group， the medium- and high-dose HLJDT groups and the risperidone group showed markedly reduced biting and aggression （P<0.05， P<0.01） and prolonged attack latency （P<0.01）. MOG， MBP， and PLP levels and MAG fluorescence intensity were significantly increased （P<0.05， P<0.01）. INOS， CD86， TNF-α， IL-6， and IL-1β levels decreased significantly （P<0.05， P<0.01）. CD22 and SHP-1 expression decreased， while p-Akt expression increased significantly （P<0.05， P<0.01）. ConclusionHLJDT may modulate CD22/SHP-1/p-Akt signaling in the VMHvl， promote the shift of MG toward an anti-inflammatory and phagocytic phenotype， enhance myelin repair， and improve agitation-like behaviors in VAD mice.

Chronic obstructive pulmonary disease （COPD） is a chronic respiratory disease that poses a significant threat to global health， exhibiting high morbidity， disability and mortality rate， with its prevention and treatment situation becoming increasingly critical. The pathogenesis of COPD is complex， and the underlying cellular and molecular biological mechanisms remain incompletely elucidated. Programmed cell death （PCD） is the process wherein cells actively undergo demise to maintain internal environmental stability in response to certain signals or specific stimuli. Contemporary medical research indicates that the dysregulation of PCD patterns such as apoptosis， necroptosis， pyroptosis， autophagy， and ferroptosis is closely related to the onset and progression of COPD. Clarifying the molecular mechanisms of PCD in COPD may provide novel perspectives for in-depth understanding and prevention of the disease. Traditional Chinese medicine （TCM） is characterized by holistic regulation. In recent years， extensive research has been conducted in the TCM field focusing on modulating apoptosis， necroptosis， pyroptosis， autophagy， and ferroptosis for the treatment of COPD， yielding remarkable achievements. Therefore， this study systematically explored the molecular mechanism of PCD in COPD and reviewed the potential mechanisms and intervention status of TCM targeting PCD in COPD， aiming to provide insights and references for the clinical prevention， treatment and in-depth research of COPD.

Chronic obstructive pulmonary disease （COPD） is a chronic respiratory disease that poses a significant threat to global health， exhibiting high morbidity， disability and mortality rate， with its prevention and treatment situation becoming increasingly critical. The pathogenesis of COPD is complex， and the underlying cellular and molecular biological mechanisms remain incompletely elucidated. Programmed cell death （PCD） is the process wherein cells actively undergo demise to maintain internal environmental stability in response to certain signals or specific stimuli. Contemporary medical research indicates that the dysregulation of PCD patterns such as apoptosis， necroptosis， pyroptosis， autophagy， and ferroptosis is closely related to the onset and progression of COPD. Clarifying the molecular mechanisms of PCD in COPD may provide novel perspectives for in-depth understanding and prevention of the disease. Traditional Chinese medicine （TCM） is characterized by holistic regulation. In recent years， extensive research has been conducted in the TCM field focusing on modulating apoptosis， necroptosis， pyroptosis， autophagy， and ferroptosis for the treatment of COPD， yielding remarkable achievements. Therefore， this study systematically explored the molecular mechanism of PCD in COPD and reviewed the potential mechanisms and intervention status of TCM targeting PCD in COPD， aiming to provide insights and references for the clinical prevention， treatment and in-depth research of COPD.

Metabolic associated fatty liver disease （MAFLD） is the main type of chronic liver disease in the world， with an increasingly higher incidence rate and a younger age of onset. At present， the treatment of MAFLD mainly depends on lifestyle intervention and comorbidity management， and there is still a lack of effective drugs for MAFLD itself. As a classic nonsteroidal anti-inflammatory drug of the salicylic acid family， aspirin can intervene in the pathological process of MAFLD by regulating lipid metabolism， relieving insulin resistance， reducing liver inflammation and oxidative stress response， exerting an anti-liver fibrosis effect， and inhibiting hepatocellular carcinoma， and therefore， it has the value of preventing disease onset， delaying disease progression， and reversing disease condition. This article systematically reviews the mechanism of action and safety of aspirin in the treatment of MAFLD， in order to provide more drug treatment options for MAFLD patients.

ObjectiveThis paper aims to investigate and evaluate the staged efficacy and safety of the representative empirical prescription of the “Zhu Ke Jiao” theory， Qijia Rougan prescription， combined with entecavir in the treatment of hepatic fibrosis in chronic hepatitis B. MethodsA multicenter randomized controlled clinical study was conducted， and 101 patients diagnosed with chronic hepatitis B-related hepatic fibrosis （CHB-HF） who met the diagnosis and inclusion criteria were randomly assigned to an observation group （Qijia Rougan prescription + entecavir） and a control group （entecavir）. The treatment duration was 24 weeks. Liver stiffness measurement （LSM）， fibrosis-4 index （FIB-4）， portal vein diameter， hepatitis B serology， biochemical indicators， hepatic fibrosis markers in serum ［hyaluronic acid （HA）， laminin （LN）， procollagen Ⅲ peptide （PⅢP）， and type Ⅳ collagen （Ⅳ-C）］， and traditional Chinese medicine syndrome scores were used as efficacy evaluation indicators. Efficacy assessments and explorations of different staged subgroups of Qijia Rougan prescription were conducted according to LSM values based on the Metavir pathological staging standard. ResultsA total of 98 cases were included for statistical analysis， with 49 cases in the observation group and 49 in the control group. The general data of the patients in both groups were comparable. Compared with the same group before treatment， the observation group showed a significant reduction in LSM and FIB-4 （P<0.01）， as well as notable improvements in LN， Ⅳ-C， and various TCM syndrome scores （P<0.05， P<0.01）. When compared to the control group after treatment， the observation group demonstrated significant improvements in LSM， FIB-4， and various TCM syndrome score indicators （P<0.05， P<0.01）， indicating that the observation group performed better than the control group. Subgroup analysis of the regression of hepatic fibrosis stages showed that compared to the same group before treatment， the observation group had better improvement in regression of stages F2 and F3 （P<0.05）. When compared to the control group after treatment， the observation group exhibited superior improvement in regression of stage F3 （P<0.05）. No adverse events occurred in either group during the treatment period. ConclusionCompared with entecavir alone， the combination of Qijia Rougan prescription and entecavir significantly improves the degree of hepatic fibrosis and clinical TCM symptoms in patients. The optimal intervention period is primarily during stage F3， which is a potential “interception” point of the “Zhu Ke Jiao” theory.

Objective To establish a highly efficient and sensitive technical system for the identification and analysis of platycodin-type saponins, systematically compare the differences in platycodin-type saponins among Platycodon grandiflorum from different producing areas, and provide scientific references for the screening of high-quality Platycodon grandiflorum resources, authenticity evaluation, and construction of standardized quality control systems. Methods A total of 45 batches of P. grandiflorum medicinal materials from 3 producing areas （Anhui, Henan, and Jilin, with 15 batches per area） were selected as research objects. Qualitative identification and semi-quantitative analysis of saponin components were performed based on ultra-high performance liquid chromatography-quadrupole-time-of-flight tandem mass spectrometry （UHPLC-Q-TOF/MS） technology. Meanwhile, two multivariate statistical methods, principal component analysis （PCA） and partial least squares-discriminant analysis （PLS-DA）, were combined to analyze the differences in platycodin-type saponins of Platycodon grandiflorus from different producing areas. Results A total of 28 saponin components were identified from Platycodon grandiflorus of the three producing areas. PCA results showed that there were minor differences in platycodin-type saponins between Henan Platycodon grandiflorus and Jilin Platycodon grandiflorus, while Anhui P. grandiflorum exhibited significant differences from both. PLS-DA further screened 15 major differential compounds. Among them, the contents of 6 components including 3''-O-acetylpolygalacin D2 and platycodin H in Anhui Platycodon grandiflorus were higher than those in Henan and Jilin Platycodon grandiflorus; platycodigenic acid A had the highest content in Jilin Platycodon grandiflorus; the contents of platycodin D3, polygalacin J, and polygalacin D were relatively higher in Henan Platycodon grandiflorus. Conclusion This study clarified the characteristic differences in core components of Platycodon grandiflorus from the three major producing areas, which provided an important theoretical basis for the screening of high-quality Platycodon grandiflorus resources, elucidation of the mechanism underlying its authenticity, and construction of a standardized quality control system.

BACKGROUND:Cervical disc herniation can cause pain in the neck and shoulder area,as well as radiating pain in the upper limbs.The incidence rate is increasing year by year and tends to affect younger individuals.Fully understanding the biomechanical characteristics of the cervical spine in adolescents is of great significance for preventing and delaying the onset of cervical disc herniation in this age group. OBJECTIVE:To reconstruct cervical spine models for both healthy adolescents and adolescent patients with cervical disc herniation utilizing finite element analysis techniques,to analyze the motion range of the C1-T1 cervical vertebrae as well as the biomechanical characteristics of the annulus fibrosus,nucleus pulposus,endplates,and the cartilage of the small joints. METHODS:A normal adolescent's cervical spine and an adolescent patient with cervical disc herniation were selected in this study.The continuous scan cervical spine CT raw image data were imported into Mimics 21.0 in DICOM format.The C1-T1 vertebrae were reconstructed separately.Subsequently,the established models were imported into the 3-Matic software for disc reconstruction.The perfected models were then imported into Hypermesh software for meshing of the vertebrae,nucleus pulposus,annulus fibrosus,and ligaments,creating valid geometric models.After assigning material properties,the final models were imported into ABAQUS software to observe the joint motion range of the C1-C7 cervical vertebrae segments under different conditions,and to analyze the biomechanical characteristics of the annulus fibrosus,nucleus pulposus,endplates,and small joint cartilage of each cervical spine segment. RESULTS AND CONCLUSION:(1)In six different conditions,the joint motion range of the C1 vertebra in the cervical spine models of both normal adolescent and adolescent patient with cervical disc herniation was higher than that of the other vertebrae.Additionally,the joint motion range of each cervical spine segment in normal adolescent was greater than that in adolescent patient with cervical disc herniation.(2)In the cervical spine model of normal adolescent,the maximum stress values in the annulus fibrosus and nucleus pulposus were found on the left side during C2-3 flexion conditions(0.43 MPa and 0.17 MPa,respectively).In the cervical spine model of adolescent patient with cervical disc herniation,the maximum stress values were found on the left side during C7-T1 flexion conditions(0.54 MPa and 0.18 MPa,respectively).(3)In the cervical spine model of normal adolescent,the maximum stress value on the endplate was found on the left side of the upper endplate of C3 during flexion conditions(1.46 MPa).In the model of adolescent patient with cervical disc herniation,the maximum stress value on the endplate was found on the left side of the lower endplate of C7 during flexion conditions(1.32 MPa).(4)In the cervical spine model of normal adolescent,the maximum stress value in the small joint cartilage was found in the C2-3 left rotation conditions(0.98 MPa).In adolescent patient with cervical disc herniation,the stress in the small joint cartilage significantly increased under different conditions,especially in C1-2,with the maximum stress found during left flexion(3.50 MPa).(5)It is concluded that compared to normal adolescent,adolescent patient with cervical disc herniation exhibits altered cervical curvature and a decrease in overall joint motion range in the cervical spine.In adolescent with cervical disc herniation,there is a significant increase in stress on the annulus fibrosus,nucleus pulposus,and endplates in the C7-T1 segment.The stress on the left articular cartilage of the C1-2 is notable.Abnormal cervical curvature may be the primary factor causing these stress changes.

BACKGROUND:The extracellular-regulated protein kinase 5(ERK5)signaling protein is essential for the survival of organisms,and resveratrol can promote osteoblast proliferation through various pathways.However,whether resveratrol can regulate osteoblast function through the ERK5 signaling protein needs further verification. OBJECTIVE:To explore the regulatory effect of ERK5 on the proliferation of MC3T3-E1 cells and related secreted proteins,and to further verify whether resveratrol can complete the above process by activating ERK5. METHODS:Mouse MC3T3-E1 preosteoblasts were treated with complete culture medium,XMD8-92(an ERK5 inhibitor),epidermal growth factor(an ERK5 activator),resveratrol alone,XMD8-92+EGF,and resveratrol+XMD8-92,respectively.Western blot assay was used to detect the expression of ERK5 and p-ERK5 proteins,proliferation-related proteins Cyclin D1,CDK4 and PCNA,and osteoblast-secreted proteins osteoprotegerin and receptor activator of nuclear factor-κB ligand in MC3T3-E1 cells of each group.The fluorescence intensity of ERK5,osteoprotegerin and receptor activator of nuclear factor-κB ligand in each group was detected by cell immunofluorescence staining,and cell proliferation was detected by EdU staining,respectively.The appropriate concentration and time of resveratrol intervention in MC3T3-E1 cells were determined by cell morphology observation and cell counting kit-8 assay. RESULTS AND CONCLUSION:The activation of ERK5 signaling protein could effectively promote the proliferation of MC3T3-E1 cells,up-regulate the osteoprotegerin/receptor activator of nuclear factor-κB ligand ratio.The appropriate concentration and time for resveratrol intervention in MC3T3-E1 cells was 5 μmol/L and 24 hours,respectively.Resveratrol could activate ERK5 signaling protein,thereby promoting osteoblast proliferation and up-regulating the osteoprotegerin/RANKL ratio.All these results indicate that resveratrol can promote the proliferation of MC3T3-E1 cells and up-regulate the osteoprotegerin/RANKL ratio by activating the ERK5 signaling protein.

[Objective] To establish a new scoring system to predict the perioperative outcomes (operation time, intraoperative blood loss, and trifecta achievement) in patients undergoing robot-assisted partial nephrectomy (RAPN) by integrating the RENAL and Mayo adhesive probability (MAP) scores. [Methods] Clinical data of 178 patients with renal cell carcinoma who underwent RAPN performed by the same surgeon in our hospital during Jan.2015 and Jan.2022 were retrospectively analyzed.The RENAL and MAP scores of all patients were calculated.Linear regression and logistic regression were used to evaluate the associations between the components of the RENAL and MAP scores (a total of 6 variables) and perioperative outcomes.The factors with significant associations were then included into logistic regression analysis to identify independent predictors for constructing an assessment system for perioperative outcomes, and the receiver operating characteristic (ROC) curve was plotted to calculate the area under the curve (AUC) to predict its efficacy. [Results] Multivariate linear regression analysis showed that tumor size (β=6.14, 95%CI: 1.93—10.34, P=0.004), exophytic rate (β=10.60, 95%CI: 3.44—17.76, P=0.004), and perinephric fat thickness (β=16.48, 95%CI: 8.52—24.45, P<0.001) were significantly associated with operation time.Tumor size (β=10.55 95%CI: 5.60—15.49, P<0.001) was associated with both intraoperative blood loss and trifecta achievement (OR=1.73, 95%CI: 1.26—2.36, P=0.001). Multivariate logistic regression analysis of these 3 factors identified tumor size (OR=9.07, 95% CI: 1.18—69.45, P=0.03) and perinephric fat thickness (OR=2.28, 95%CI: 1.86—6.04, P=0.01) as independent predictors of perioperative outcomes.Based on these findings, the tumor size and perinephric fat thickness (RP) scoring was constructed, which demonstrated better predictive ability than RENAL score or MAP score alone (RP vs.RENAL vs.MAP: 0.766 vs.0.548 vs.0.684). [Conclusion] The RP score includes fewer variables than the RENAL and MAP scores but outperforms them.

ObjectiveTo establish steroid-induced osteonecrosis of the femoral head （SANFH） cell model by using dexamethasone （DEX）-induced bone marrow mesenchymal stem cells （BMSCs） and demonstrate that Gushing Granules （GSNs） exert an improving effect by activating the phosphatidylinositol-3-kinase/protein kinase B/B-lymphoma-2 gene related promoter （PI3K/Akt/Bad） signalling pathway. MethodsFirstly， SD rats were orally administered with drugs at a dose of 0.9 g·kg^-1 to prepare GSN-containing serum， and CCK-8 screening was used to determine the optimal dosage and duration of action. Then， BMSCs were cultured and treated with 1×10^-6 mol·L^-1 DEX， 10% GSN-containing serum， and inhibitor LY294002 of PI3K/Akt signalling pathway for 24 hours to model and group SANFH cells. Cell viability and proliferation were detected by using CCK-8 assay kit and EdU staining kit. Flow cytometry was used to detect cell apoptosis. An alkaline phosphatase （ALP） assay kit was employed to detect ALP expression. In order to detect the PI3K/Akt/Bad signalling pathway and protein and mRNA expression of apoptosis-related proteins such as apoptosis regulatory factors B-cell lymphoma-2 gene （Bcl-2）， and Bcl-2-associated X protein （Bax）， osteocalcin （OCN）， and Collagen Ⅰ， we used Western blot and Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR）. ResultsThe CCK-8 assay kit determined that the optimal dosage for GSN-containing serum is 10%， and the duration of action is 48 hours. After modelling and grouping the cells in each group， the detection results showed that the SANFH model group had significantly lower cell viability， cell proliferation， and ALP expression， as well as protein and mRNA expressions of PI3K， Akt， Bad， Bcl-2， OCN， and Collagen I compared to the blank group. The nucleic acid and protein levels of the Bax index and the cell apoptosis rate detected by flow cytometry significantly increased （P<0.05，P<0.01）. After treatment with GSN-containing serum， cell viability， cell proliferation， and ALP expression， as well as expressions of PI3K， Akt， Bad， Bcl-2， OCN， and Collagen Ⅰ nucleic acids and proteins were significantly increased， while the nucleic acid and protein levels of the Bax index and the cell apoptosis rate detected by flow cytometry significantly decreased（P<0.05，P<0.01）. Compared with the GSN drug-containing serum group， the simultaneous treatment with the inhibitor LY294002 and GSN drug-containing serum reversed the improvement effect of GSN. Specifically， the cell viability， cell proliferation， ALP expression， and the nucleic acid and protein levels of PI3K， Akt， Bad， Bcl-2， OCN， and Collagen Ⅰ were all significantly decreased， while the nucleic acid and protein levels of the Bax index and the cell apoptosis rate detected by flow cytometry were significantly increased （P<0.05， P<0.01）. ConclusionGSNs antagonize DEX-induced apoptosis of BMSCs by activating the PI3K/Akt/Bad signalling pathway， providing a scientific theoretical basis for the clinical treatment of SANFH with GSNs.