OBJECTIVE To investigate the mechanism of Xibining Ⅱ formula in alleviating synovial inflammation and fibrosis in knee osteoarthritis （KOA） rats based on Janus kinase 2 （JAK2）/signal transducer and activator of transcription 3 （STAT3） pathway. METHODS Seventy-five male SD rats were randomly divided into sham operation group （Sham group）， KOA group， Xibining Ⅱ low-dose group （XBNⅡ-L group， 4 g/kg）， Xibining Ⅱ high-dose group （XBNⅡ-H group， 8 g/kg）， and Xibining Ⅱ high-dose combined with STAT3 activator Colivelin trifluoroacetate （C-TFA） group [C-TFA group， 8 g/kg Xibining Ⅱ+ 1.0 mg/（kg·d） C-TFA]， with 15 rats in each group. Except for the Sham group， the KOA model was established by anterior cruciate ligament transection in the other groups. After successful modeling， each group was given corresponding drugs by intragastric administration and （or） intraperitoneal injection once daily for 28 consecutive days. After the last medication， the pathological changes of synovial tissue of knee joint in each group were evaluated and the indicators were calculated. The levels of serum inflammatory factors were detected. The positive expressions of phosphorylated JAK2 （p-JAK2） and phosphorylated STAT3 （p-STAT3） in synovial tissue of the knee joint were detected. The expressions of JAK2/STAT3 pathway-related proteins and mRNAs in synovial tissue were detected. RESULTS Compared with the Sham group， the synovial lining cells in the KOA group showed significant proliferation and disordered arrangement； the Krenn score， fibrosis ratio， positive area percentage of p-JAK2 and p-STAT3， p-JAK2/JAK2 and p-STAT3/STAT3， protein expression of Collagen-Ⅰ and α -smooth muscle actin， the mRNA expression of JAK2， STAT3， Collagen-Ⅰ and α -smooth muscle actin， as well as serum levels of interleukin-1β and interleukin-18 were significantly increased （ P ＜0.05）. Compared with the KOA group， the above pathological changes were significantly improved in each dose group of Xibining Ⅱ formula， and all indicators were significantly decreased （ P ＜0.05）， with the XBNⅡ-H group showing better effects than the XBNⅡ-L group （ P ＜0.05）. Compared with the XBNⅡ-H group， the above pathological damages were aggravated in the C-TFA group， and all indicators were significantly worsened （ P ＜0.05）. CONCLUSIONS Xibining Ⅱ formula can alleviate synovial inflammation and fibrosis in KOA rats， and its mechanism may be related to inhibiting the activation of JAK2/STAT3 pathway.

ObjectiveTo investigate the possible mechanism of action of Xibining Formula （膝痹宁） for cartilage damage in knee osteoarthritis （KOA） through the cyclic guanosine-adenosine monophosphate synthase （cGAS）- stimulator of interferon genes （STING） signaling pathway. MethodsFifty C57BL/6J mice were randomly divided into five groups （10 per group）， sham operation group， KOA model group， low-dose Xibining Formula group， high-dose Xibining Formula group， and high-dose Xibining Formula + agonist group. The KOA models were constructed using the destabilization of the medial meniscus （DMM） method in all groups but the sham surgery group. Two weeks after surgery， the low- and high-dose Xibining Formula groups were administered Xibining Formula at doses of 3.58 g/（kg·d） and 14.32 g/（kg·d） respectively via gavage. The high-dose Xibining Formula + agonist group received 14.32 g/（kg·d） of Xibining Formula via gavage followed by an intraperitoneal injection of Vadimezan （DMXAA） at 25 mg/kg. The sham surgery group and the KOA model group mice were given an equivalent volume of normal saline at 5 ml/（kg·d） via gavage， once daily for four consecutive weeks. Serum levels of tumor necrosis factor-alpha （TNF-α）， interleukin-1β （IL-1β）， and interleukin-6 （IL-6） were measured by ELISA； pathological changes in cartilage tissue were observed using hematoxylin-eosin （HE） staining and Safranin O-Fast Green staining. Pathological changes were scored according to the Mankin scoring system； the levels of cartilage tissue matrix regulation-related indicators such as matrix metalloproteinase 3 （MMP3）， matrix metalloproteinase 13 （MMP13）， a disintegrin and metalloproteinase with thrombospondin motifs 5 （ADAMTS）， type-Ⅱ collagen （CⅡ） and aggregated proteoglycan （Aggrecan）， and also cGAS-STING pathway-related protein and mRNA expression levels were detected by Western blot and qPCR methods. ResultsCompared with the sham surgery group， the KOA model group showed severe cartilage edge destruction， significantly increased Mankin scores， significantly decreased protein and mRNA expression levels of COLⅡ and Aggrecan， and significantly increased protein and mRNA expression levels of cGAS， STING， MMP3， MMP13， and ADAMTS5 （P＜0.01）. Compared with the control group， serum level of IL-6， IL-1β， TNF-α in all the intervented groups decreased （P＜0.01）， while compared with high-dose Xibining Formula group， level of IL-6， IL-1β， and TNF-α in low-dose Xibining Formula group and high-dose Xibining Formula + agonist group increased （P＜0.01）. Compared with the KOA model group， all the intervention groups exhibited alleviated cartilage pathological changes， signi-ficantly reduced Mankin scores， significantly increased protein and mRNA expression levels of COLⅡ and Aggrecan， and significantly decreased protein and mRNA expression levels of cGAS， STING， MMP3， MMP13， and ADAMTS5 （P＜0.01）. Compared with high-dose Xibining Formula group， high-dose Xibining Formula + agonist group showed cartilage edge destruction， significantly increased Mankin scores， significantly decreased protein and mRNA expression levels of COLⅡ and Aggrecan， and increased protein and mRNA expression levels of cGAS， STING， MMP3， MMP13， and ADAMTS5 （P＜0.01）. ConclusionXibining Formula may improve KOA cartilage damage by inhibiting the cGAS-STING signaling pathway， decreasing matrix degradation-related proteins， and elevating matrix composition-related proteins.

OBJECTIVE To analyze the differences in chemical composition of mussels from Shengsi,Zhoushan in different har-vest months,and to compare the differences in the composition of mussels from different origins,so as to provide ideas for the compre-hensive utilization of its resources.METHODS Ultra-high performance liquid chromatography-triple quadrupole mass spectrometry(UHPLC-QqQ-MS)and spectrophotometry were used to analyze and evaluate the contents of nucleosides,amino acids,water-soluble proteins,total sugars and polysaccharides in mussels from Shengsi,Zhoushan in 12 months of the year and from 5 different origins;principal component analysis(PCA),partial least squares discriminant method(PLS-DA)and TOPSIS method were used to compre-hensively evaluate mussels.RESULTS A total of 16 amino acids and 11 nucleosides were detected in mussels.The average content of total amino acids in Shengsi mussels throughout the year was 4 851.74 μg·g-1,the average content of total nucleosides was 921.40 μg·g-1,and the average contents of water-soluble protein,polysaccharides,and total sugars were 51.32 mg·g-1,74.39 μg·g-1,and 417.22 mg·g-1,respectively.The nucleosides of Shengsi mussels were the highest in March and April,the ami-no acids and water-soluble proteins were the highest in April and May,and the polysaccharides and total sugars were the highest in Oc-tober and November.The PCA and PLS-DA results of the chemical components of different resources showed that there were great differences in Shengsi mussel samples harvested in different seasons.The entropy weight TOPSIS analysis showed that the comprehen-sive scores of Shengsi mussels in March and April(S7 and S8)were better than those in other areas,and the comprehensive score of Shengsi mussels in April(S8)was the highest,which was determined to be the best harvesting month.CONCLUSION The comparison results of multi-type resource chemistry show that there are great differences in the chemical compo-sition of Shengsi mussels in different harvesting seasons;the quality of Shengsi mussels is better than that of other areas;April is the best harvesting season,providing a reference for the quality evaluation and comprehensive development and utilization of mussels.

Objective:To evaluate the stability of percutaneous screw fixation for minimally invasive treatment of intra-articular calcaneal fractures using three-dimensional finite element analysis.Methods:CT scan was performed on the calcaneus of a normal adult for three-dimensional reconstruction. The DICOM data were imported into Mimics software to establish a model of a Sanders type IIB intra-articular calcaneal fracture. Based on the Essex-Lopresti classification of posterior facet morphology, the model was subdivided into two subtypes: tongue-type and depression-type. The calcaneus was divided into four fragments: sustentaculum tali, posterior tuberosity, anterior process (three points), and posterior articular surface (one surface). Two types of fixation methods, classical lateral anatomical plates and combinations of percutaneous screws, were simulated and performed. A three-dimensional finite element analysis was conducted by applying a stress combination of 420 N on the posterior subtalar articular surface, 200 N on the middle subtalar articular surface, and 300 N at the Achilles tendon insertion point. The maximum displacement and von Mises stress values of each bone fragment and implant were recorded to evaluate the biomechanical stability. For clinical validation, 34 patients with Sanders type IIB calcaneal fractures from Orthopedics Department of the Sixth Affiliated People's Hospital of Shanghai Jiao Tong University were treated with percutaneous reduction and screw fixation using the following configurations.Results:Under simulated stress, the A4 group with medial support screws in the tongue-type fracture subgroup demonstrated minimal overall calcaneal displacement (0.22 mm) and internal fixation displacement (0.14 mm). For the depression-type, the B2 group with medial support screws showed lower maximum stress in the calcaneus and internal fixation, at 22.04 MPa and 41.14 MPa, respectively, along with the lowest overall displacement (0.14 mm). The peak stress of all groups of implants remained below the material yield strength. The A4 and B2 protocols were applied to 15 cases of tongue-type calcaneal fractures and 19 cases of collapse-type calcaneal fractures. At the final follow-up The American Orthopaedic Foot & Ankle Society ankle-hindfoot score scale was 86.1±5.82 and 87.2±5.18, respectively, while the visual analog scale for pain was 1.60±1.24 and 1.58±1.02, respectively.Conclusions:Percutaneous screw fixation provided reliable stability for Sanders type IIB calcaneal fractures. The fixation configuration incorporating a medial support screw offers superior biomechanical performance in both tongue-type and depression-type fractures, representing an optimized minimally invasive technique with strong clinical applicability.

AIM:This study aimed to investigate the inhibitory effects and potential mechanisms of cyasterone(CYA)on inflammation and apoptosis of chondrocytes in knee osteoarthritis(KOA).METHODS:A rat model of KOA was established through anterior cruciate ligament transection(ACLT).Rats were randomly divided into 5 groups(n=6 in each group):normal control(NC),ACLT,ACLT+CYA(10 mg/kg),ACLT+CYA+SR9009(BMAL1 inhibitor),and ACLT+CYA+LY294002(PI3K inhibitor).Pathological changes in cartilage were evaluated using hematoxylin-eosin(HE)and safranin O/fast green staining,graded according to the Osteoarthritis Research Society International(OARSI)system.Immunohistochemistry was employed to measure the expression levels of BMAL1,phosphorylated phosphati-dylinositol 3-kinase(p-PI3K),phosphorylated protein kinase B(p-AKT)and phosphorylated nuclear factor-κB(p-NF-κB)in cartilage.An in vitro KOA model was created by stimulating rat chondrocytes with interleukin-1β(IL-1β).Cell vi-ability was assessed using the CCK-8 assay,while enzyme-linked immunosorbent assay(ELISA)was used to quantify pro-inflammatory cytokines(IL-6,IL-1β and TNF-α).Apoptosis was analyzed via flow cytometry,and the protein expression levels of BMAL1,PI3K,p-PI3K,AKT,p-AKT,NF-κB and p-NF-κB were evaluated using Western blot.RESULTS:In vivo,the rats in ACLT group exhibited significant chondrocyte degradation and lacunae formation compared with NC group,confirming the successful establishment of the KOA model.The rats in ACLT+CYA,ACLT+CYA+SR9009 and ACLT+CYA+LY294002 groups showed improved cartilage integrity compared with ACLT group,with reduced OARSI scores(P<0.05),increased BMAL1 expression(P<0.05),and decreased levels of p-PI3K,p-AKT and p-NF-κB(P<0.05).In vitro,the chondrocytes in IL-1β+CYA,IL-1β+CYA+SR9009 and IL-1β+CYA+LY294002 groups exhibited lower levels of IL-6,IL-1β and TNF-α(P<0.05),decreased apoptosis rates(P<0.01),increased BMAL1 protein ex-pression(P<0.05),and reduced p-PI3K/PI3K,p-AKT/AKT and p-NF-κB/NF-κB ratios(P<0.05),compared with IL-1β group.CONCLUSION:Cyasterone alleviates chondrocyte inflammation and apoptosis in KOA by activating BMAL1,which subsequently inhibits the phosphorylation of PI3K/AKT/NF-κB signaling pathway.

Objective:To evaluate the stability of percutaneous screw fixation for minimally invasive treatment of intra-articular calcaneal fractures using three-dimensional finite element analysis.Methods:CT scan was performed on the calcaneus of a normal adult for three-dimensional reconstruction. The DICOM data were imported into Mimics software to establish a model of a Sanders type IIB intra-articular calcaneal fracture. Based on the Essex-Lopresti classification of posterior facet morphology, the model was subdivided into two subtypes: tongue-type and depression-type. The calcaneus was divided into four fragments: sustentaculum tali, posterior tuberosity, anterior process (three points), and posterior articular surface (one surface). Two types of fixation methods, classical lateral anatomical plates and combinations of percutaneous screws, were simulated and performed. A three-dimensional finite element analysis was conducted by applying a stress combination of 420 N on the posterior subtalar articular surface, 200 N on the middle subtalar articular surface, and 300 N at the Achilles tendon insertion point. The maximum displacement and von Mises stress values of each bone fragment and implant were recorded to evaluate the biomechanical stability. For clinical validation, 34 patients with Sanders type IIB calcaneal fractures from Orthopedics Department of the Sixth Affiliated People's Hospital of Shanghai Jiao Tong University were treated with percutaneous reduction and screw fixation using the following configurations.Results:Under simulated stress, the A4 group with medial support screws in the tongue-type fracture subgroup demonstrated minimal overall calcaneal displacement (0.22 mm) and internal fixation displacement (0.14 mm). For the depression-type, the B2 group with medial support screws showed lower maximum stress in the calcaneus and internal fixation, at 22.04 MPa and 41.14 MPa, respectively, along with the lowest overall displacement (0.14 mm). The peak stress of all groups of implants remained below the material yield strength. The A4 and B2 protocols were applied to 15 cases of tongue-type calcaneal fractures and 19 cases of collapse-type calcaneal fractures. At the final follow-up The American Orthopaedic Foot & Ankle Society ankle-hindfoot score scale was 86.1±5.82 and 87.2±5.18, respectively, while the visual analog scale for pain was 1.60±1.24 and 1.58±1.02, respectively.Conclusions:Percutaneous screw fixation provided reliable stability for Sanders type IIB calcaneal fractures. The fixation configuration incorporating a medial support screw offers superior biomechanical performance in both tongue-type and depression-type fractures, representing an optimized minimally invasive technique with strong clinical applicability.

OBJECTIVE To analyze the differences in chemical composition of mussels from Shengsi,Zhoushan in different har-vest months,and to compare the differences in the composition of mussels from different origins,so as to provide ideas for the compre-hensive utilization of its resources.METHODS Ultra-high performance liquid chromatography-triple quadrupole mass spectrometry(UHPLC-QqQ-MS)and spectrophotometry were used to analyze and evaluate the contents of nucleosides,amino acids,water-soluble proteins,total sugars and polysaccharides in mussels from Shengsi,Zhoushan in 12 months of the year and from 5 different origins;principal component analysis(PCA),partial least squares discriminant method(PLS-DA)and TOPSIS method were used to compre-hensively evaluate mussels.RESULTS A total of 16 amino acids and 11 nucleosides were detected in mussels.The average content of total amino acids in Shengsi mussels throughout the year was 4 851.74 μg·g-1,the average content of total nucleosides was 921.40 μg·g-1,and the average contents of water-soluble protein,polysaccharides,and total sugars were 51.32 mg·g-1,74.39 μg·g-1,and 417.22 mg·g-1,respectively.The nucleosides of Shengsi mussels were the highest in March and April,the ami-no acids and water-soluble proteins were the highest in April and May,and the polysaccharides and total sugars were the highest in Oc-tober and November.The PCA and PLS-DA results of the chemical components of different resources showed that there were great differences in Shengsi mussel samples harvested in different seasons.The entropy weight TOPSIS analysis showed that the comprehen-sive scores of Shengsi mussels in March and April(S7 and S8)were better than those in other areas,and the comprehensive score of Shengsi mussels in April(S8)was the highest,which was determined to be the best harvesting month.CONCLUSION The comparison results of multi-type resource chemistry show that there are great differences in the chemical compo-sition of Shengsi mussels in different harvesting seasons;the quality of Shengsi mussels is better than that of other areas;April is the best harvesting season,providing a reference for the quality evaluation and comprehensive development and utilization of mussels.

AIM:This study aimed to investigate the inhibitory effects and potential mechanisms of cyasterone(CYA)on inflammation and apoptosis of chondrocytes in knee osteoarthritis(KOA).METHODS:A rat model of KOA was established through anterior cruciate ligament transection(ACLT).Rats were randomly divided into 5 groups(n=6 in each group):normal control(NC),ACLT,ACLT+CYA(10 mg/kg),ACLT+CYA+SR9009(BMAL1 inhibitor),and ACLT+CYA+LY294002(PI3K inhibitor).Pathological changes in cartilage were evaluated using hematoxylin-eosin(HE)and safranin O/fast green staining,graded according to the Osteoarthritis Research Society International(OARSI)system.Immunohistochemistry was employed to measure the expression levels of BMAL1,phosphorylated phosphati-dylinositol 3-kinase(p-PI3K),phosphorylated protein kinase B(p-AKT)and phosphorylated nuclear factor-κB(p-NF-κB)in cartilage.An in vitro KOA model was created by stimulating rat chondrocytes with interleukin-1β(IL-1β).Cell vi-ability was assessed using the CCK-8 assay,while enzyme-linked immunosorbent assay(ELISA)was used to quantify pro-inflammatory cytokines(IL-6,IL-1β and TNF-α).Apoptosis was analyzed via flow cytometry,and the protein expression levels of BMAL1,PI3K,p-PI3K,AKT,p-AKT,NF-κB and p-NF-κB were evaluated using Western blot.RESULTS:In vivo,the rats in ACLT group exhibited significant chondrocyte degradation and lacunae formation compared with NC group,confirming the successful establishment of the KOA model.The rats in ACLT+CYA,ACLT+CYA+SR9009 and ACLT+CYA+LY294002 groups showed improved cartilage integrity compared with ACLT group,with reduced OARSI scores(P<0.05),increased BMAL1 expression(P<0.05),and decreased levels of p-PI3K,p-AKT and p-NF-κB(P<0.05).In vitro,the chondrocytes in IL-1β+CYA,IL-1β+CYA+SR9009 and IL-1β+CYA+LY294002 groups exhibited lower levels of IL-6,IL-1β and TNF-α(P<0.05),decreased apoptosis rates(P<0.01),increased BMAL1 protein ex-pression(P<0.05),and reduced p-PI3K/PI3K,p-AKT/AKT and p-NF-κB/NF-κB ratios(P<0.05),compared with IL-1β group.CONCLUSION:Cyasterone alleviates chondrocyte inflammation and apoptosis in KOA by activating BMAL1,which subsequently inhibits the phosphorylation of PI3K/AKT/NF-κB signaling pathway.

Objective:To investigate the application value of the maximum standardized uptake value (SUVmax) of 18F prostate-specific membrane antigen (PSMA) PET/CT combined with the minimum apparent diffusion coefficient (ADCmin) of biparametric magnetic resonance imaging (bpMRI) in predicting pathological upgrading after radical prostatectomy (RP) for prostate cancer. Methods:The data of 89 patients with localized prostate cancer treated at Beijing Hospital from April 2019 to October 2023 were retrospectively analysed. The average age of patients was (68.4±7.0) years old, with prostate-specific antigen (PSA) level of 7.7 (5.4, 12.9) ng/ml, prostate volume of 34.6 (26.9, 47.1) ml, tumor diameter of 1.3 (1.0, 1.8) cm, prostate imaging reporting and data system(PI-RADS) score of 5 in 29 cases (32.6%), clinical stage ≥T 3 in 13 cases (14.6%). There were 31 cases (34.8%) in group 1 of targeted biopsy International Society of Urological Pathology (ISUP)grading groups, 36 cases (40.4%) in group 2, 11 cases (12.4%) in group 3, and 11 cases (12.4%) in group 4. All patients underwent 18F-PSMA PET/CT and bpMRI examinations before RP. The index lesion, identified as the highest Gleason score in pathological whole-mount sections, were outlined. SUVmax and ADCmin values were calculated from the images' region of interest. Pathological upgrading was defined as the post-RP grade group higher than the targeted-biopsy grade group. Clinical data of patients with and without pathological upgrading were compared. Spearman correlation coefficient analysis was used to assess the correlation between SUVmax and ADCmin. Multivariate logistic regression analysis was conducted to evaluate the factors influencing pathological upgrading. Receiver operating characteristic (ROC) curve analysis was employed to assess the predictive value of each indicator for pathological upgrading. Results:Among the 89 cases, 31 cases (34.8%) experienced pathological upgrading. Compared with the patients without pathological upgrading, the SUVmax [11.3 (8.1, 16.4) vs. 6.7 (4.6, 9.2)], SUVmax/ADCmin ratio [3.1 (2.0, 4.6) vs. 1.4 (0.9, 2.1)], PSA [9.8 (6.3, 15.6) ng/ml vs. 7.1 (5.1, 10.5) ng/ml], PSA density [0.3 (0.2, 0.5) ng/ml 2 vs. 0.2 (0.1, 0.3) ng/ml 2], and post-RP ISUP grade group [≥3 group 17 cases (54.8%) vs. 13 cases(22.4%) ]were higher in patients with pathological upgrading, while ADCmin [3.8 (3.0, 5.3) ×10 -4 mm 2/s vs. 5.2 (3.6, 6.1)×10 -4 mm 2/s] and targeted biopsy ISUP grade group [≤2 group 27 cases(87.1%) vs. 40 cases(69.0%) ] were lower (all P<0.05). Spearman analysis showed a negative correlation between SUVmax and ADCmin ( R = -0.227, P = 0.032). Multivariate logistic regression analysis revealed that SUVmax ( OR = 1.108, 95% CI 1.020-1.238), ADCmin ( OR=0.607, 95% CI 0.390-0.874), and SUVmax/ADCmin ratio ( OR = 1.815, 95% CI 1.282-2.949) independently predicted pathological upgrading. The AUC of the SUVmax/ADCmin ratio for predicting pathological upgrading (AUC = 0.817) was higher than that of SUVmax (AUC = 0.774) and ADCmin (AUC=0.686), indicating a higher predictive efficiency. Conclusions:SUVmax, ADCmin, and SUVmax/ADCmin ratio can independently predict pathological upgrading in targeted biopsy of prostate cancer. The SUVmax/ADCmin ratio has a stronger predictive value for pathological upgrading.

Objective To observe the clinical efficacy of Quxie Capsule combined with fruquintinib in the treatment of metastatic colorectal cancer(mCRC).Methods A prospective,non-randomized,controlled study was used to collect patients with mCRC who planned to receive third-line treatment after second-line treatment at Xiyuan Hospital of China Academy of Chinese Medical Sciences,Guang'anmen Hospital of China Academy of Chinese Medical Sciences,Dongfang Hospital Beijing University of Chinese Medicine,and Xinjiang Uygur Autonomous Region Hospital of Traditional Chinese Medicine.The treatment group received Quxie Capsule combined with fruquintinib.The control group was treated with fruquintinib.The primary outcome measure was third-line overall survival(OS),and the secondary outcome measure was third-line progression-free survival(PFS).Results A total of 142 patients with mCRC were included in this study(79 in the treatment group and 63 in the control group).The median OS(mOS)was 19.0 months in the treatment group and 8.1 months in the control group,and the difference was statistically significant[HR=0.285,95%CI(0.183,0.436),P<0.001].The median PFS(mPFS)in the treatment group was 7 months,mPFS in the control group was 2 months,and the difference was statistically significant[HR=0.248,95%CI(0.165,0.362),P<0.001].In subgroups,such as age,gender,primary site,peritoneal metastasis,and genotype,mOS in the treatment group was longer than in the control group(P<0.001).Multivariate COX proportional hazard model analysis showed that peritoneal metastasis was an independent prognostic factor and the risk of death increased 2.14 times.The combination with Quxie Capsule was a protective factor,reducing the risk of death by 76.8%.Conclusion The Quxie Capsule combined with fruquintinib can prolong mOS survival and mPFS of mCRC treated in the third-line stage.