BACKGROUND:Sarcopenia is an age-related condition characterized by the loss of skeletal muscle mass,strength,and/or physical function.Currently,effective treatments for sarcopenia remain limited.A new therapeutic approach to improve symptoms and prognosis of sarcopenia patients clinically was important.OBJECTIVE:To explore the effects of canine adipose-derived mesenchymal stem cells and their exosomes on a dexamethasone-induced sarcopenia in mice.METHODS:Mesenchymal stem cells were isolated and cultured from canine adipose tissue,and identified and functionally evaluated through flow cytometry and differentiation assays for osteogenesis,adipogenesis,and chondrogenesis.Subsequently,exosomes from adipose-derived mesenchymal stem cells were extracted and characterized using transmission electron microscopy,western blot assay,and nanocoulter tracking analysis.In vitro,the effects of canine adipose-derived mesenchymal stem cells and their exosomes on myotube growth and the expression of muscle atrophy-related genes were investigated using dexamethasone-induced C2C12 myotube atrophy and aging C2C12 models.In vivo,a dexamethasone-induced mouse sarcopenia model was established and received intraperitoneal or intravenous injection of canine adipose-derived mesenchymal stem cells.Therapeutic efficacy was assessed through mouse rotarod performance,histopathological analysis,and muscle atrophy-related genes testing.RESULTS AND CONCLUSION:(1)The isolated canine adipose-derived mesenchymal stem cells highly expressed CD73,CD90,and CD105,and lowly expressed MHC-Ⅱ,CD14,CD19,CD34,and CD45,and successfully differentiated into osteoblasts,adipocytes,and chondrocytes in vitro.(2)The adipose-derived mesenchymal stem cells-derived exosomes met the identification criteria in terms of particle size,electron microscopy morphology,and positive expression of specific markers.(3)Compared to the dexamethasone-induced C2C12 atrophy group,treatment with adipose-derived mesenchymal stem cells and their exosomes promoted the recovery and growth of myotubes,inhibited the expression of muscle atrophy-related genes MuRF1 and Atrogin-1.(4)Compared to the aging C2C12 group,adipose-derived mesenchymal stem cells and their exosomes significantly enhanced the recovery and growth of aged muscle tubes in aging cells.(5)Compared to the control group,the rotarod time in dexamethasone-induced sarcopenia model mice was significantly decreased(P＜0.01).After 7 days(P＜0.01,P＜0.01)and 10 days(P＜0.01,P＜0.05)of adipose-derived mesenchymal stem cells treatment via intraperitoneal and intravenous injection,rotarod time was significantly increased,respectively.After 14 days,all treatment groups showed longer rotarod times than the model group,although with no significant differences between them.(6)Compared to the control group,the cross-sectional area of anterior tibial muscle in the model group was significantly reduced(P＜0.01),and it was significantly increased after intraperitoneal and intravenous administration of adipose-derived mesenchymal stem cells(P＜0.05,P＜0.01).(7)Compared to the model group,intraperitoneal and intravenous administration of adipose-derived mesenchymal stem cells significantly inhibited the mRNA expression of MuRF1 and Atrogin-1 genes(P＜0.01,P＜0.01,P＜0.01,P＜0.01).The results indicated that adipose-derived mesenchymal stem cells and their exosomes promoted recovery and growth of atrophic myotube cells by inhibiting the expression of muscle atrophy-related genes,and both intraperitoneal and intravenous administration of adipose-derived mesenchymal stem cells provided good therapeutic effects on sarcopenia in mice.

BACKGROUND:With changing lifestyles and aging,sagittal spinal imbalance has become a common orthopedic issue significantly affecting knee and pelvic function.Understanding the impact of sagittal spinal imbalance and its compensatory mechanisms is crucial for improving the clinical management of chronic pain.OBJECTIVE:To evaluate the alignment of the spine-pelvis-lower extremities using whole-body EOS imaging,analyze the correlation between spinal sagittal imbalance and knee joint parameters,and explore their compensatory mechanisms.METHODS:A total of 71 patients with chronic low back pain or patellofemoral pain who visited Department of Orthopedics,First Affiliated Hospital of Soochow University between January 1,2021 and December 31,2023 were included.Radiographic measurements were performed using whole-body EOS to determine pelvic tilt,pelvic incidence,lumbar lordosis,sagittal vertical axis,global tilt,hip-knee-angle,knee flexion angle,lateral distal femoral angle,and medial proximal tibial angle.Patients were classified into normal group(pelvic incidence-lumbar lordosis＜10°),compensated group(10°＜pelvic incidence-lumbar lordosis＜20°),and decompensated group(pelvic incidence-lumbar lordosis＞20°)based on the SRS-Schwab spinal deformity classification according to pelvic incidence-lumbar lordosis difference.The differences in radiographic parameters among the groups were analyzed.The differences in American Knee Society Knee Score and Oswestry Disability Index scores were compared among each group.Patients were divided into chronic low back pain group and non-chronic low back pain group,patellofemoral pain group and non-patellofemoral pain group based on clinical symptoms,and the relationship between radiographic parameter differences and clinical symptoms was analyzed.RESULTS AND CONCLUSION:(1)When pelvic incidence-lumbar lordosis was less than 20°,lateral distal femoral angle and medial proximal tibial angle tended to stabilize.When pelvic incidence-lumbar lordosis was greater than 20°,it showed a linear correlation with lateral distal femoral angle and medial proximal tibial angle,with lateral distal femoral angle increasing and medial proximal tibial angle decreasing with increasing pelvic incidence-lumbar lordosis values.(2)Compared with the normal group,the compensated group had significantly increased pelvic tilt(P＜0.01),while knee joint parameters hip-knee-angle and knee flexion angle showed no significant differences;the decompensated group showed significant increases in pelvic tilt(P＜0.01),and decreases in hip-knee-angle,and knee flexion angle(P＜0.01).Compared with the compensated group,the decompensated group showed a significant decrease in hip-knee-angle(P＜0.05),but had no significant differences in pelvic tilt and knee flexion angle.(3)Compared with the non-patellofemoral pain group,patients with patellofemoral pain had significant decreases in spinal lumbar lordosis,lateral distal femoral angle,and medial proximal tibial angle(P＜0.05)and a significant increase in pelvic incidence-lumbar lordosis(P＜0.05).(4)Patients with low back pain had significant differences in radiographic parameters compared with the non-chronic low back pain group(P＜0.05).(5)Compared with the normal group,both the compensated and decompensated groups showed a significant decrease in American Knee Society Knee Score scores and a significant increase in Oswestry Disability Index scores(P＜0.05).Compared with the compensated group,the decompensated group showed a significant decrease in American Knee Society Knee Score scores and a significant increase in Oswestry Disability Index scores(P＜0.05).(6)Pelvic incidence-lumbar lordosis values increased with age and were higher in females compared with males.(7)This study systematically reveals the spine and lower limbs play an important role in disease progression and clinical symptoms.Associated symptoms low back pain and patellofemoral pain are related to the stability of the spine-pelvis-lower extremity alignment.Furthermore,spinal sagittal imbalance is more severe in elderly and female patients.

BACKGROUND:Pediatric flexible flatfoot is a common foot deformity that often leads to foot pain and reduced quality of life.OBJECTIVE:To explore the relationship between radiographic parameters and clinical efficacy of subtalar arthroereisis in the treatment of pediatric flexible flatfoot.METHODS:A retrospective study was conducted on 56 pediatric patients(mean age of 11.8 years)who underwent subtalar arthroereisis at Guangzhou Orthopedic Hospital between January 2022 and May 2023.All patients underwent detailed radiographic examinations and clinical evaluations before and after surgery,including the American Orthopaedic Foot & Ankle Society Ankle-Hindfoot score and Visual Analog Scale score.Paired t-tests and independent t-tests were used to compare changes in radiographic parameters and clinical scores before and after surgery.Correlation analyses were conducted to evaluate the relationship between radiographic parameters and clinical outcomes.RESULTS AND CONCLUSION:(1)All radiographic parameters significantly improved during the 8 to 12-month follow-up after surgery(P＜0.001).(2)Clinical evaluation results indicated that the American Orthopaedic Foot & Ankle Society Ankle-Hindfoot score significantly improved from 66.2±6.0 preoperatively to 91.3±5.8 postoperatively,and the Visual Analog Scale score significantly decreased from 3.1±0.8 preoperatively to 1.3±0.8 postoperatively(P＜0.001).(3)Independent t-tests showed a significant difference in postoperative the first metatarsal angle and Visual Analog Scale score grades(P=0.043),with a smaller the first metatarsal angle associated with less postoperative pain;preoperative lateral arch angle showed a significant difference between the"excellent"and"good"groups in postoperative American Orthopaedic Foot & Ankle Society Ankle-Hindfoot scores(P=0.033),suggesting that a smaller preoperative posterior arch angle might predict better postoperative foot function recovery.(4)Correlation analysis showed that preoperative posterior arch angle(r=-0.486,P＜0.01)and heel pitch angle(r=-0.344,P＜0.01)were significantly negatively correlated with postoperative American Orthopaedic Foot & Ankle Society Ankle-Hindfoot,while preoperative medial longitudinal arch angle(r=0.293,P＜0.05)was significantly positively correlated with postoperative American Orthopaedic Foot & Ankle Society Ankle-Hindfoot.Postoperative medial longitudinal arch angle(r=0.331,P＜0.05)and lateral arch angle(r=0.387,P＜0.01)were significantly positively correlated with postoperative American Orthopaedic Foot & Ankle Society Ankle-Hindfoot,whereas postoperative Bohler's angle(r=-0.272,P＜0.05),posterior arch angle(r=-0.461,P＜0.01),and heel pitch angle(r=-0.318,P＜0.01)were significantly negatively correlated with postoperative American Orthopaedic Foot & Ankle Society Ankle-Hindfoot.(5)It is concluded that subtalar arthroereisis is significantly effective in correcting pediatric flexible flatfoot,and improvements in radiographic parameters are closely related to clinical efficacy.Preoperative and postoperative radiographic evaluations can serve as important reference indicators for predicting postoperative clinical outcomes,guiding clinicians to optimize treatment plansand rehabilitation programs.

BACKGROUND:Sarcopenia is an age-related condition characterized by the loss of skeletal muscle mass,strength,and/or physical function.Currently,effective treatments for sarcopenia remain limited.A new therapeutic approach to improve symptoms and prognosis of sarcopenia patients clinically was important.OBJECTIVE:To explore the effects of canine adipose-derived mesenchymal stem cells and their exosomes on a dexamethasone-induced sarcopenia in mice.METHODS:Mesenchymal stem cells were isolated and cultured from canine adipose tissue,and identified and functionally evaluated through flow cytometry and differentiation assays for osteogenesis,adipogenesis,and chondrogenesis.Subsequently,exosomes from adipose-derived mesenchymal stem cells were extracted and characterized using transmission electron microscopy,western blot assay,and nanocoulter tracking analysis.In vitro,the effects of canine adipose-derived mesenchymal stem cells and their exosomes on myotube growth and the expression of muscle atrophy-related genes were investigated using dexamethasone-induced C2C12 myotube atrophy and aging C2C12 models.In vivo,a dexamethasone-induced mouse sarcopenia model was established and received intraperitoneal or intravenous injection of canine adipose-derived mesenchymal stem cells.Therapeutic efficacy was assessed through mouse rotarod performance,histopathological analysis,and muscle atrophy-related genes testing.RESULTS AND CONCLUSION:(1)The isolated canine adipose-derived mesenchymal stem cells highly expressed CD73,CD90,and CD105,and lowly expressed MHC-Ⅱ,CD14,CD19,CD34,and CD45,and successfully differentiated into osteoblasts,adipocytes,and chondrocytes in vitro.(2)The adipose-derived mesenchymal stem cells-derived exosomes met the identification criteria in terms of particle size,electron microscopy morphology,and positive expression of specific markers.(3)Compared to the dexamethasone-induced C2C12 atrophy group,treatment with adipose-derived mesenchymal stem cells and their exosomes promoted the recovery and growth of myotubes,inhibited the expression of muscle atrophy-related genes MuRF1 and Atrogin-1.(4)Compared to the aging C2C12 group,adipose-derived mesenchymal stem cells and their exosomes significantly enhanced the recovery and growth of aged muscle tubes in aging cells.(5)Compared to the control group,the rotarod time in dexamethasone-induced sarcopenia model mice was significantly decreased(P＜0.01).After 7 days(P＜0.01,P＜0.01)and 10 days(P＜0.01,P＜0.05)of adipose-derived mesenchymal stem cells treatment via intraperitoneal and intravenous injection,rotarod time was significantly increased,respectively.After 14 days,all treatment groups showed longer rotarod times than the model group,although with no significant differences between them.(6)Compared to the control group,the cross-sectional area of anterior tibial muscle in the model group was significantly reduced(P＜0.01),and it was significantly increased after intraperitoneal and intravenous administration of adipose-derived mesenchymal stem cells(P＜0.05,P＜0.01).(7)Compared to the model group,intraperitoneal and intravenous administration of adipose-derived mesenchymal stem cells significantly inhibited the mRNA expression of MuRF1 and Atrogin-1 genes(P＜0.01,P＜0.01,P＜0.01,P＜0.01).The results indicated that adipose-derived mesenchymal stem cells and their exosomes promoted recovery and growth of atrophic myotube cells by inhibiting the expression of muscle atrophy-related genes,and both intraperitoneal and intravenous administration of adipose-derived mesenchymal stem cells provided good therapeutic effects on sarcopenia in mice.

ObjectivePolygoni Multiflori Radix is a commonly used tonic traditional Chinese medicine （TCM） in clinical practice， but liver injury has often been reported in recent years. Some related preparations containing Polygoni Multiflori Radix have been reported by the National Medical Products Administration many times for the risk of liver injury. This has caused extensive discussion on the potential toxicity of TCM in China and abroad， which has limited the clinical use of Polygoni Multiflori Radix to some extent. To understand the adverse reactions of Polygoni Multiflori Radix， the safe and rational use of Polygoni Multiflori Radix in clinical practice was discussed. MethodsThe pharmacovigilance thought of modern Chinese medicine and the TCM pharmacovigilance system framework of ''identification of poison， use of poison， anti-poison， and detoxification'' were employed to mine the relevant toxicity records， usage and dosage， processing compatibility， and contraindication of taking Polygoni Multiflori Radix in ancient books. The drug safety information of Polygoni Multiflori Radix was summarized by comparing with modern reports. ResultsA total of 74 ancient books related to Polygoni Multiflori Radix were included， suggesting that the toxicity of Polygoni Multiflori Radix was recognized in ancient times. The main chemical components of Polygoni Multiflori Radix had both efficacy and toxicity， and the adverse reactions may be related to long-term use， excessive use， and individual differences. The results showed that the toxic components of Polygoni Multiflori Radix could be reduced by peeling， steaming with black beans， and processing without iron tools. The toxic effects of Polygoni Multiflori Radix could be reduced by the compatibility of Polygoni Multiflori Radix with Poria， Psoraleae Fructus， and Cistanches Herba. ConclusionReasonable dosage， standard processing， correct compatibility， and syndrome differentiation are the key points to standardize the use of Polygoni Multiflori Radix and reduce the incidence of adverse reactions. Clinically， the toxicity classification of TCM should be strengthened， and the susceptible population should be prioritized. The detection indicators and early warning mechanisms should be improved， and precise drug dosage and course of treatment should be guaranteed. These measures can ensure the safe use of Polygoni Multiflori Radix.

ObjectivePolygoni Multiflori Radix is a commonly used tonic traditional Chinese medicine （TCM） in clinical practice， but liver injury has often been reported in recent years. Some related preparations containing Polygoni Multiflori Radix have been reported by the National Medical Products Administration many times for the risk of liver injury. This has caused extensive discussion on the potential toxicity of TCM in China and abroad， which has limited the clinical use of Polygoni Multiflori Radix to some extent. To understand the adverse reactions of Polygoni Multiflori Radix， the safe and rational use of Polygoni Multiflori Radix in clinical practice was discussed. MethodsThe pharmacovigilance thought of modern Chinese medicine and the TCM pharmacovigilance system framework of ''identification of poison， use of poison， anti-poison， and detoxification'' were employed to mine the relevant toxicity records， usage and dosage， processing compatibility， and contraindication of taking Polygoni Multiflori Radix in ancient books. The drug safety information of Polygoni Multiflori Radix was summarized by comparing with modern reports. ResultsA total of 74 ancient books related to Polygoni Multiflori Radix were included， suggesting that the toxicity of Polygoni Multiflori Radix was recognized in ancient times. The main chemical components of Polygoni Multiflori Radix had both efficacy and toxicity， and the adverse reactions may be related to long-term use， excessive use， and individual differences. The results showed that the toxic components of Polygoni Multiflori Radix could be reduced by peeling， steaming with black beans， and processing without iron tools. The toxic effects of Polygoni Multiflori Radix could be reduced by the compatibility of Polygoni Multiflori Radix with Poria， Psoraleae Fructus， and Cistanches Herba. ConclusionReasonable dosage， standard processing， correct compatibility， and syndrome differentiation are the key points to standardize the use of Polygoni Multiflori Radix and reduce the incidence of adverse reactions. Clinically， the toxicity classification of TCM should be strengthened， and the susceptible population should be prioritized. The detection indicators and early warning mechanisms should be improved， and precise drug dosage and course of treatment should be guaranteed. These measures can ensure the safe use of Polygoni Multiflori Radix.

OBJECTIVE To investigate the effects and potential mechanism of curcumin on neurological injury in neonatal rats with bacterial meningitis based on the signal transducer and activator of transcription 1（ STAT1）/ nucleotide-binding domain leucine- rich repeat and pyrin domain-containing receptor 3 （NLRP3） signaling pathway. METHODS Neonatal rats， with an equal number of males and females， were randomly divided into control group， model group， curcumin low-dose （Cur-L）， medium-dose （Cur- M） and high-dose （Cur-H） groups， and Cur-H+STAT1 transcription enhancer [2-（1，8-naphthyridin-2-yl）phenol] group （Cur-H+2- NP group）， with 15 rats in each group. Except for the control group， rats in other groups were injected with a suspension of group B Streptococcus （1×104 cfu/mL， 10 μL） into the cerebellomedullary cistern to establish a bacterial meningitis model. After successful model establishment， rats in Cur-L， Cur-M and Cur-H groups were intraperitoneally injected with 1.25， 2.5 and 5 mg/kg curcumin， respectively， and those in the Cur-H+2-NP group were intraperitoneally injected with 5 mg/kg curcumin and 0.5 mg/kg 2- NP， once a day， for 3 consecutive weeks. After the last administration， modified Loeffler score was conducted， white blood cells （WBC） count in cerebrospinal fluid as well as the contents of inflammatory factors [tumor necrosis factor-α， interleukin-6 （IL-6）， IL-1β and IL-18]， brain water content and blood-brain barrier permeability were detected； the histopathological changes of hippocampus and cortex tissues were observed. The percentage of apoptosis in hippocampal/cortical tissue cells， the positive expression of ionized calcium-binding adapter molecule-1 （Iba-1）， the co-localization of Iba-1 and NLRP3， as well as the expressions of proteins related to the STAT1/NLRP3 signaling pathway （phosphorylated STAT1， NLRP3， apoptosis-associated speck-like protein containing a CARD， gasdermin D， caspase-1， IL-1β and IL-18） were examined. RESULTS Compared with the control group， the neurons in the hippocampal/cortical tissues of rats in the model group exhibited significant morphological abnormalities， accompanied by neuronal edema and necrosis， as well as infiltration of inflammatory cells. The modified Loeffler score and the number of Nissl bodies were significantly decreased/reduced in the model group， while the WBC count， levels of inflammatory factors， brain water content， blood-brain barrier permeability， HE staining score， number of degenerated neurons， percentage of apoptotic cells， positive expression of Iba-1， percentage of Iba-1 and NLRP3 co-localization- positive cells， and expressions of pathway-related proteins were all significantly rose/increased/upregulated （P＜0.05）. Compared with the model group， the histopathological changes in the hippocampal/cortical tissues of rats in all curcumin dosage groups were alleviated to varying degrees， with significant improvements in all quantitative indicators （P＜0.05）； conversely， 2-NP significantly reversed the ameliorative effects of curcumin on these quantitative indicators （P＜0.05）. CONCLUSIONS Curcumin can alleviate cerebral edema and blood-brain barrier damage， reduce neuroinflammation， inhibit cell apoptosis and pyroptosis， and thereby alleviate neuronal injury in neonatal rats with bacterial meningitis. The underlying mechanism may be related to the inhibition of the STAT1/NLRP3 signaling pathway.

BACKGROUND This study aims to develop and validate a machine learning-based in-hospital mortality predictive model for acute aortic syndrome (AAS) in the emergency department (ED) and to derive a simplified version suitable for rapid clinical application. METHODS: In this multi-center retrospective cohort study, AAS patient data from three hospitals were analyzed. The modeling cohort included data from the First Affiliated Hospital of Zhengzhou University and the People’s Hospital of Xinjiang Uygur Autonomous Region, with Peking University Third Hospital data serving as the external test set. Four machine learning algorithms—logistic regression (LR), multilayer perceptron (MLP), Gaussian naive Bayes (GNB), and random forest (RF)—were used to develop predictive models based on 34 early-accessible clinical variables. A simplified model was then derived based on five key variables (Stanford type, pericardial effusion, asymmetric peripheral arterial pulsation, decreased bowel sounds, and dyspnea) via Least Absolute Shrinkage and Selection Operator (LASSO) regression to improve ED applicability. RESULTS: A total of 929 patients were included in the modeling cohort, and 210 were included in the external test set. Four machine learning models based on 34 clinical variables were developed, achieving internal and external validation AUCs of 0.85-0.90 and 0.73-0.85, respectively. The simplified model incorporating five key variables demonstrated internal and external validation AUCs of 0.71-0.86 and 0.75-0.78, respectively. Both models showed robust calibration and predictive stability across datasets. CONCLUSION: Both kinds of models were built based on machine learning tools, and proved to have certain prediction performance and extrapolation.

ObjectiveThis study aimed to investigate the optimal compatibility ratio of the Chuanxiong Rhizoma-Carthami Flos （CR-CF） couplet medicines in ischemic stroke （IS） therapy and its pharmacological action mechanism， providing a scientific basis for the clinical application of CR-CF couplet medicines in IS therapy. MethodsThe chemical composition of CR-CF was analyzed using liquid chromatography mass spectrometry （LC-MS/MS）. The contents of eight characteristic chemical components in aqueous extracts of CR-CF with common clinical compatibility ratios （1∶1， 1∶2， 1∶3， 3∶2， 2∶1） were determined by ultra-high performance liquid chromatography（UHPLC）. An oxygen-glucose deprivation/reoxygenation （OGD/R）-induced mouse hippocampal neuron HT22 cell injury model was established， and cells were treated with different CR-CF compatibility ratios. The collaborative index （CI） was calculated by using CompuSyn software. A cerebral artery occlusion/reperfusion （MCAO/R） model of rats was induced by using the modified Longa suture method. The rats were divided into the sham group， model group， Chuanxiong Rhizoma （CR） group （1.3 g·kg^-1）， Carthami Flos （CF） group （3.9 g·kg^-1）， CR-CF group （5.2 g·kg^-1）， and edaravone group （5 mg·kg^-1）. Neuronal defect scores were assessed by the Longa scoring method. Cerebral infarction volume was measured by 2，3，5-triphenyltetrazolium chloride（TTC） staining. Neuronal damage was observed via hematoxylin-eosin （HE） staining. Neuronal apoptosis of rats was detected by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling （TUNEL） staining， and the expression of apoptosis-related proteins was analyzed by Western blot. Label-free proteomics was employed to screen differentially expressed proteins， and Western blot was used to examine the expression of phosphatidylinositol 3-kinase/protein kinase B（PI3K/Akt） signaling pathway-related proteins. Finally， molecular docking was performed to predict the binding affinity of eight active constituents in CR-CF （1∶3） with PI3K. ResultsWhen CR-CF was combined at a 1∶3 ratio， the total content of the eight active constituents in the extract was the highest， and the synergistic protective effect on OGD/R-injured HT22 cells was the strongest （CI=0.308）. Animal experiments showed that compared with the sham group， the model group exhibited increased neuroecological score points （P<0.01）， larger cerebral infarction volumes （P<0.01）， aggravated brain tissue damage， elevated neuronal apoptosis （P<0.01）， and increased B-cell lymphoma-2（Bcl-2）-associated X protein （Bax）/Bcl-2 and cleaved Cysteinyl aspartate specific proteinase-3/Cysteinyl aspartate specific proteinase-3 （cleaved Caspase-3/Caspase-3） ratios （P<0.01）. Compared with the model group， CR-CF （1∶3） significantly reduced neurological scores （P<0.01）， significantly decreased cerebral infarction volume （P<0.01）， alleviated brain tissue damage， inhibited neuronal apoptosis （P<0.01）， and significantly lowered the Bax/Bcl-2 and cleaved Caspase-3/Caspase-3 ratios （P<0.01）. The therapeutic effect of CR-CF （1∶3） was superior to that of CR or CF alone. Proteomic analysis revealed that CR-CF （1∶3） activated the PI3K/Akt signaling pathway. Validation experiments demonstrated that compared with the sham group， the model group showed obviously reduced p-PI3K/PI3K and p-Akt/Akt （P<0.05）. Compared with the model group， p-PI3K/PI3K and p-Akt/Akt ratios （P<0.05） obviously increased. Compared with the CR-CF group， the 2-（4-morpholinyl）-8-phenyl-4H-1-benzopyran-4-one LY294002 inhibitor+CR-CF group exhibited obviously decreased p-PI3K/PI3K and p-Akt/Akt （P<0.05）. Molecular docking results indicated that the active constituents of CR-CF （1∶3） had strong binding affinity with PI3K. ConclusionThe CR-CF couplet medicines at a 1∶3 ratio exhibit optimal synergistic effects， and their anti-IS mechanism is closely related to activation of the PI3K/Akt signaling pathway and inhibition of neuronal apoptosis.

ObjectiveTo explore the clinical efficacy of oral administration of modified Tuoli Xiaodusan on postoperative patients with perianal abscess， and its effects on related inflammatory factors and signal transducers and activators of transcription protein 3 （STAT3）/vascular endothelial growth factor （VEGF） signaling pathways. MethodsFrom January 2023 to December 2023 in Inner Mongolia hospital of traditional Chinese medicine， 60 postoperative patients with perianal abscess who met the inclusion criteria were selected. They were divided into a treatment group and a control group using the random number table method， with 30 cases in each group. The control group received conventional treatment， while the treatment group received additional treatment with modified Tuoli Xiaodusan on the basis of the control group. The course of treatment in both groups was three weeks. On the day of operation and on the 7^th， 14^th and 21^st day after operation， enzyme-linked immunosorbent assay （ELISA） was used to measure the expression levels of serum interleukin-1β （IL-1β）， interleukin-6 （IL-6）， and tumor necrosis factor-α （TNF-α）. Hematoxylin eosin （HE） staining was used to observe the pathological morphology of pathological tissue. Western blot was used to measure the levels of phosphorylated STAT3 （p-STAT3） and vascular endothelial growth factor （VEGF） proteins， and real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） was used to determine the expression level of VEGF mRNA. The clinical efficacy of the two groups was compared according to the wound pain， secretion volume score， and healing rate of patients on the 3^rd， 7^th， 14^th， and 21^st day after operation. ResultsThe total effective rate of the treatment group was higher than that of the control group （P<0.05）. For intra-group comparison， the pain score of the control group decreased at each time period （P<0.05）， and the healing rate increased （P<0.05）. The secretion volume score decreased on the 14^th and 21^st days after operation （P<0.05）. The pain score and secretion volume score of the treatment group decreased at each time period （P<0.05）， and the healing rate increased （P<0.05）. The levels of various inflammatory factors decreased in both groups （P<0.05）. Compared with those on the surgical day， the levels of p-STAT3 and VEGF proteins in the wound tissue of the two groups were different on the 7^th and 21^st days after operation （P<0.05）. There were significant differences in VEGF mRNA levels in wound tissue between the two groups at each time period （P<0.01）. For inter-group comparison， on the 7^th and 14^th days after operation， the pain score in the treatment group was lower than that in the control group. On the 7^th， 14^th and 21^st days after operation， the secretion volume scores and healing rate of the treatment group were better than those of the control group （P<0.05）. The levels of various inflammatory factors in the treatment group were lower than those in the control group （P<0.05）， and the decline rate was faster （P<0.05）. On the 7^th day after operation， the levels of p-STAT3， VEGF protein， and VEGF mRNA in the wound tissue of the treatment group were higher than those in the control group （P<0.05）. HE staining showed that the inflammatory cell infiltration in the treatment group decreased faster. The cell arrangement was more orderly， and new blood vessel lumens were visible. There were no abnormalities in the safety observation indexes of all patients during the study period. ConclusionModified Tuoli Xiaodusan can relieve wound pain after perianal abscess surgery， reduce secretions， and improve wound healing rate. The mechanism may be reducing the levels of serum IL-1β， IL-6， and TNF-α， reducing the inflammatory response of the wound， upregulating the expression of p-STAT3 and VEGF proteins， and stimulating the STAT3/VEGF signaling pathway， thereby accelerating angiogenesis and promoting wound healing.