BACKGROUND:Previous studies of the research group have found that icariin-containing serum can delay the progression of knee osteoarthritis,promote chondrocyte proliferation and stem cell cartilage differentiation in rats,but there is still a lack of sufficient basis for clinical application.OBJECTIVE:To investigate the repair effect of icariin-containing serum on lipopolysaccharide-induced inflammatory damage of human chondrocytes.METHODS:The effect of icariin-containing serum on chondrocyte viability was detected by cell counting kit-8 method,and the optimal volume fraction and time of icariin-containing serum were screened.The cells were then divided into blank group,lipopolysaccharide group,icariin-containing serum group and lipopolysaccharide+icariin-containing serum group.After grouping,immunofluorescence was used to detect the secretion of type Ⅱ collagen in chondrocytes in each group.Real-time PCR was used to detect the expression of related genes.RESULTS AND CONCLUSION:(1)Icariin-containing serum showed good biosafety characteristics for human chondrocytes,and the cell viability reached the highest level after 48 hours of intervention when the icariin-containing serum volume fraction was 15％,and the follow-up experiments were carried out according to the conditions.(2)Compared with the blank group,lipopolysaccharide significantly inhibited the expression of type Ⅱ collagen in chondrocytes,while icariin-containing serum showed a positive mobilization effect,which could effectively promote the secretion of type Ⅱ collagen in chondrocytes under normal and inflammatory conditions.(3)The mRNA expression of type Ⅱ collagen and Aggrecan in chondrocytes decreased significantly under lipopolysaccharide stimulation,and the mRNA expression levels of matrix metalloproteinase 13 and a disintegrin-like and metalloproteinase with thrombospondin motifs-5 increased significantly.Icariin-containing serum promoted the mRNA expression of type Ⅱ collagen in human chondrocytes under inflammatory conditions and reduced the mRNA expression of matrix metalloproteinase 13 and a disintegrin-like and metalloproteinase with thrombospondin motifs-5 in chondrocytes after lipopolysaccharide intervention.Therefore,these findings indicate that the icariin-containing serum has good safety for human chondrocytes and plays an important role in maintaining the normal physiological functions of chondrocytes,promoting the synthesis of extracellular matrix,and inhibiting the secretion of inflammatory factors.

BACKGROUND:Previous studies of the research group have found that icariin-containing serum can delay the progression of knee osteoarthritis,promote chondrocyte proliferation and stem cell cartilage differentiation in rats,but there is still a lack of sufficient basis for clinical application.OBJECTIVE:To investigate the repair effect of icariin-containing serum on lipopolysaccharide-induced inflammatory damage of human chondrocytes.METHODS:The effect of icariin-containing serum on chondrocyte viability was detected by cell counting kit-8 method,and the optimal volume fraction and time of icariin-containing serum were screened.The cells were then divided into blank group,lipopolysaccharide group,icariin-containing serum group and lipopolysaccharide+icariin-containing serum group.After grouping,immunofluorescence was used to detect the secretion of type Ⅱ collagen in chondrocytes in each group.Real-time PCR was used to detect the expression of related genes.RESULTS AND CONCLUSION:(1)Icariin-containing serum showed good biosafety characteristics for human chondrocytes,and the cell viability reached the highest level after 48 hours of intervention when the icariin-containing serum volume fraction was 15％,and the follow-up experiments were carried out according to the conditions.(2)Compared with the blank group,lipopolysaccharide significantly inhibited the expression of type Ⅱ collagen in chondrocytes,while icariin-containing serum showed a positive mobilization effect,which could effectively promote the secretion of type Ⅱ collagen in chondrocytes under normal and inflammatory conditions.(3)The mRNA expression of type Ⅱ collagen and Aggrecan in chondrocytes decreased significantly under lipopolysaccharide stimulation,and the mRNA expression levels of matrix metalloproteinase 13 and a disintegrin-like and metalloproteinase with thrombospondin motifs-5 increased significantly.Icariin-containing serum promoted the mRNA expression of type Ⅱ collagen in human chondrocytes under inflammatory conditions and reduced the mRNA expression of matrix metalloproteinase 13 and a disintegrin-like and metalloproteinase with thrombospondin motifs-5 in chondrocytes after lipopolysaccharide intervention.Therefore,these findings indicate that the icariin-containing serum has good safety for human chondrocytes and plays an important role in maintaining the normal physiological functions of chondrocytes,promoting the synthesis of extracellular matrix,and inhibiting the secretion of inflammatory factors.

Objective:To investigate the application value of needle-knife accurate fistulo-tomy (NKAF) for difficult biliary cannulation during endoscopic retrograde cholangiopancreato-graphy (ERCP).Methods:The retrospective and descriptive study was conducted. The clinicopatho-logical data of 137 patients with difficult biliary cannulation during ERCP at Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine between January 2021 and December 2022 were collected. There were 51 males and 86 females, aged (69±13)years. All 137 patients received NKAF for cannulation during ERCP. Observation indicators: (1) surgical situations; (2) complications. Measurement data with normal distribution were represented as Mean± SD. Count data were repre-sented as absolute numbers. Results:(1) Surgical situations. Of 137 patients, 136 cases had succe-ssful cannulation, 1 case had failed cannulation with NKAF following unsuccessful double-guidewire technique. In the 136 successful cases, the endoscope was straightened in 42 cases, left in a long position in 37 cases, and maintained in the standard position in 57 cases. The cannulation time was (90±8)s. (2) Complications. The serum amylase at postoperative 6 hours in the 136 successful cases was (163±23)U/L. No patient developed post-ERCP pancreatitis. Of the 136 patients with successful cannulation, one case experienced post-sphincterotomy bleeding, which was observed oozing from the papillary orifice on emergency gastroscopy. The patient was successfully controlled with endoscopic clips.Conclusion:NKAF is safe and effective for difficult biliary cannulation during ERCP.

Objective To analyze the motion,deformation,and adhesion behavior of circulating tumor cells(CTCs)in bifurcated microvessels,reveal their mechanical properties under different flow conditions and explore their role in the process of cancer metastasis.Methods A cell-scale modeling approach was adopted,combining the immersed boundary-lattice Boltzmann method(IB-LBM)and the adhesive-dynamics model to simulate the motion and adhesion behavior of circulating tumor cells in microvessels.Results The adhesion behavior of CTCs was significantly influenced by the Reynolds number(Re)and the surface elastic moduli of cells.Under the condition of Re=0.003,the adhesion behavior of CTCs was the most stable;CTCs with a lower surface elastic modulus exhibited greater deformation during adhesion and demonstrated stronger adhesive forces.Conclusions The mechanical properties of CTCs and flow field conditions jointly determine their transport and adhesion behavior in microvessels.The levels of Re and surface elastic modulus play a critical role in the deformation and adhesion of CTCs.The study of the adhesion characteristics of CTCs provides mechanistic insights and new potential directions for cancer prevention and treatment research.

Objective To explore the protective effect and possible mechanism of modified Shenqi Dihuang Decoction on podocytes in db/db mice based on ROS/NLRP3/GSDMD signaling pathway.Methods Fifty 8-week-old male db/db mice(SPF grade)were randomly divided into the model group,losartan group and TCM low-,medium-and high-dosage groups,with 10 mice in each group.Ten heterozygous db/m mice served as the blank group.Interventions were administered respectively for 12 weeks.The body mass,random blood glucose,serum creatinine,blood urea nitrogen and 24 h urinary protein content were detected,HE,PAS,PASM,Masson and Sirius red staining was used to observe the morphology of renal tissue,transmission electron microscopy was used to observe the ultrastructure of renal tissue,fluorescent probes were used to observe the release of ROS in renal tissue,immunofluorescence staining was used to detect the expression of Nephrin,NLRP3,Cleaved Caspase-1 and GSDMD-N in renal tissue,and Western blot was used to detect the expression of NLRP3,Cleaved Caspase-1,GSDMD-N,IL-1β,IL-18,Nephrin,Podocin,PODXL,WT-1 and Desmin proteins.Results Compared with the blank group,the body mass and random blood glucose of the model group mice significantly increased(P<0.05),and the contents of serum creatinine,blood urea nitrogen and 24 h urinary protein were significantly increased(P<0.05);glomerular hypertrophy,dilation of renal glomeruli and tubules,thickening of basement membrane,matrix proliferation in mesangial area,abnormal deposition of collagen fibers in renal interstitium,accompanied by damage to renal tubular epithelial structure and focal glomerulosclerosis,significant increase in type Ⅰ collagen deposition,extensive fusion of podocyte processes,and scattered electron dense material in the basement membrane or subepithelial layer;the ROS content in renal tissue significantly increased(P<0.05),and the protein expression of NLRP3,Cleaved Caspase-1,GSDMD-N,IL-1β,IL-18 and Desmin significantly increased(P<0.05),the protein expression of Nephrin,Podocin,PODXL and WT1 significantly decreased(P<0.05).Compared with the model group,the body mass and random blood glucose of mice in each dosage of TCM group were relatively stable,the contents of serum creatinine,blood urea nitrogen and 24 h urinary protein decreased;the pathological damage to renal tissue was reduced,the ultrastructure of podocytes was improved,and the density of podocytes increased;the ROS content decreased,and the protein expression of NLRP3,Cleaved Caspase-1,GSDMD-N,IL-1β,IL-18 and Desmin decreased,while the protein expression of Nephrin,Podocin,WT1 and PODXL increased.With the dosage of modified Shenqi Dihuang Decoction increased,the improvement effect gradually strengthened,and the differences in TCM high-dose group was statistically significant(P<0.05).Conclusion Modified Shenqi Dihuang Decoction can protects podocytes in db/db mice,potentially by modulating the ROS/NLRP3/GSDMD signaling pathway.

Objective To analyze the motion,deformation,and adhesion behavior of circulating tumor cells(CTCs)in bifurcated microvessels,reveal their mechanical properties under different flow conditions and explore their role in the process of cancer metastasis.Methods A cell-scale modeling approach was adopted,combining the immersed boundary-lattice Boltzmann method(IB-LBM)and the adhesive-dynamics model to simulate the motion and adhesion behavior of circulating tumor cells in microvessels.Results The adhesion behavior of CTCs was significantly influenced by the Reynolds number(Re)and the surface elastic moduli of cells.Under the condition of Re=0.003,the adhesion behavior of CTCs was the most stable;CTCs with a lower surface elastic modulus exhibited greater deformation during adhesion and demonstrated stronger adhesive forces.Conclusions The mechanical properties of CTCs and flow field conditions jointly determine their transport and adhesion behavior in microvessels.The levels of Re and surface elastic modulus play a critical role in the deformation and adhesion of CTCs.The study of the adhesion characteristics of CTCs provides mechanistic insights and new potential directions for cancer prevention and treatment research.

Objective To analyze the biomechanical responses after small incision lenticule extraction(SMILE)based on personalized biomechanical parameters of the human eye.Methods Through the results from the correlation analysis between corneal stromal elastic modulus and biomechanical parameters,the cornea elastic modulus was predicted and the material parameters were obtained.Based on clinical measurement data,52 personalized myopic human eye models were reconstructed to analyze the corneal biomechanical response after SMILE.Results The biomechanical response of the cornea varied from patients,and the vertex displacement and stress of the corneal surface increased or decreased after SMILE.On average,when residual stromal thickness(RST)ranged from 278 μm to 332 μm and IOP was 16-20 mmHg(1 mmHg=0.133 kPa),the change of vertex displacement and stress on the corneal surface after SMILE were less than those under IOP=11-16 mmHg.Under RST＞332 μm and IOP=11-16 mmHg,the corneal biomechanics was relatively stable.In addition,the corrected diopters of patients increased,and the deformation of corneal surface after SMILE was more drastic.Conclusions RST and IOP are important factors influencing corneal biomechanics.The material parameters of corneal tissues were predicted based on corneal biomechanical parameters.The cutting profiles and surgical parameters of SMILE may be optimized through analyzing the surgical effect after refractive surgery by reconstructing personalized finite element model of human eyes.

Objective To explore the protective effect and possible mechanism of modified Shenqi Dihuang Decoction on podocytes in db/db mice based on ROS/NLRP3/GSDMD signaling pathway.Methods Fifty 8-week-old male db/db mice(SPF grade)were randomly divided into the model group,losartan group and TCM low-,medium-and high-dosage groups,with 10 mice in each group.Ten heterozygous db/m mice served as the blank group.Interventions were administered respectively for 12 weeks.The body mass,random blood glucose,serum creatinine,blood urea nitrogen and 24 h urinary protein content were detected,HE,PAS,PASM,Masson and Sirius red staining was used to observe the morphology of renal tissue,transmission electron microscopy was used to observe the ultrastructure of renal tissue,fluorescent probes were used to observe the release of ROS in renal tissue,immunofluorescence staining was used to detect the expression of Nephrin,NLRP3,Cleaved Caspase-1 and GSDMD-N in renal tissue,and Western blot was used to detect the expression of NLRP3,Cleaved Caspase-1,GSDMD-N,IL-1β,IL-18,Nephrin,Podocin,PODXL,WT-1 and Desmin proteins.Results Compared with the blank group,the body mass and random blood glucose of the model group mice significantly increased(P<0.05),and the contents of serum creatinine,blood urea nitrogen and 24 h urinary protein were significantly increased(P<0.05);glomerular hypertrophy,dilation of renal glomeruli and tubules,thickening of basement membrane,matrix proliferation in mesangial area,abnormal deposition of collagen fibers in renal interstitium,accompanied by damage to renal tubular epithelial structure and focal glomerulosclerosis,significant increase in type Ⅰ collagen deposition,extensive fusion of podocyte processes,and scattered electron dense material in the basement membrane or subepithelial layer;the ROS content in renal tissue significantly increased(P<0.05),and the protein expression of NLRP3,Cleaved Caspase-1,GSDMD-N,IL-1β,IL-18 and Desmin significantly increased(P<0.05),the protein expression of Nephrin,Podocin,PODXL and WT1 significantly decreased(P<0.05).Compared with the model group,the body mass and random blood glucose of mice in each dosage of TCM group were relatively stable,the contents of serum creatinine,blood urea nitrogen and 24 h urinary protein decreased;the pathological damage to renal tissue was reduced,the ultrastructure of podocytes was improved,and the density of podocytes increased;the ROS content decreased,and the protein expression of NLRP3,Cleaved Caspase-1,GSDMD-N,IL-1β,IL-18 and Desmin decreased,while the protein expression of Nephrin,Podocin,WT1 and PODXL increased.With the dosage of modified Shenqi Dihuang Decoction increased,the improvement effect gradually strengthened,and the differences in TCM high-dose group was statistically significant(P<0.05).Conclusion Modified Shenqi Dihuang Decoction can protects podocytes in db/db mice,potentially by modulating the ROS/NLRP3/GSDMD signaling pathway.

Objective To investigate the relationship between plasma von willebrand factory-lytic protease (ADAMTS13) level and the severity of the disease and its prognostic value in patients with endometriosis (EMS). Methods 130 patients with EMS treated in the hospital from January 2019 to December 2022 were retrospectively selected. Plasma ADAMTS13 level was detected by enzyme-linked immunosorbent assay (ELISA),and its correla-tion with American Fertility Society (r-AFS) stage and endometriosis Health Status Scale (EHP-30) score was analyzed. The 1-year prognosis was recorded,and the risk factors of poor prognosis were analyzed by logistic regression. Receiver operating characteristic curve (ROC) was plotted to evaluate the predictive value of plasma ADAMTS13 levels in patients with EMS. Results The plasma ADAMTS13 level of EMS patients decreased signifi-cantly with the increase of r-AFS stage,and was negatively correlated with the score of EHP-30 (P<0.001). Multiple factors showed that low plasma ADAMTS13 level,bilateral location of pelvic lesions and high r-AFS stage were independent risk factors for poor prognosis (all P<0.05). ROC analysis showed that the area under the curve (AUC) of plasma ADAMTS13 was 0.889 (cut-off point 13.315,sensitivity 0.931,specificity 0.690). Conclusion Plasma ADAMTS13 level is negatively correlated with the severity of EMS,and is an independent risk factor for poor prognosis of EMS patients,and has a certain predictive value for prognosis of EMS patients.

Objective:To explore the value of amide proton transfer weighted imaging (APTWI) combined with human epidermal growth factor receptor 2 (HER2) expression in predicting pathological complete response (pCR) after neoadjuvant chemotherapy (NAC) in breast cancer.Methods:The study was a cross-sectional study. Clinicopathological [estrogen receptor (ER), progesterone receptor (PR), HER2, Ki-67 status, and molecular subtypes] and imaging data were retrospectively analyzed in 100 female patients who had invasive ductal carcinoma of the breast confirmed pathologically by preoperative puncture in the Henan Cancer Hospital from May 2023 to May 2024. All patients underwent MRI, including enhanced MRI, APTWI, and diffusion-weighted imaging (DWI) before NAC. The reference enhanced MRI images were segmented into lesions using the threshold extraction method, and the three-dimensional region of interest within the tumor was automatically outlined by the software and replicated in the amide proton transfer map generated by APTWI and the apparent diffuse coefficient (ADC) map generated by DWI. The magnetization transfer ratio asymmetry (MTRasym) value and the ADC value were measured, respectively. Tumor response to NAC was assessed using the Miller-Payne grading system, where Grade 5 indicated pCR and Grades 1-4 were classified as non-pCR. Independent sample t-tests and χ2 tests were used to compare clinical pathological and imaging parameters between pCR and non-pCR patients. Statistically significant variables were included in multivariate logistic regression to identify independent predictors of pCR. The diagnostic performance of individual and combined indicators for pCR was evaluated using receiver operating characteristic curves and the area under the curve (AUC). DeLong′s test was used to compare AUCs. Results:There were 39 pCR and 61 non-pCR patients. Significant differences were observed between the pCR and non-pCR patients in molecular subtypes, ER, PR, HER2, and Ki-67 statuses ( P<0.05). Pre-treatment MTRasym values were significantly higher in the pCR patients compared to the non-pCR patients ( P=0.005), whereas ADC values showed no statistical difference ( P=0.372). Multivariate logistic regression analysis showed HER2 positivity ( OR=5.87, 95% CI 1.99-17.30, P=0.001) and MTRasym values>2.61% (OR=4.39, 95% CI 1.37-14.08, P=0.013) was independent predictors of pCR after NAC. HER2 positivity combined with MTRasym value>2.61% predicted pCR after NAC in breast cancer with AUC of 0.819, which was superior to HER2 positivity and MTRasym value alone in predicting efficacy ( Z=3.91, P<0.001; Z=2.63, P=0.009). Conclusions:The MTRasym value of pre-treatment APTWI is valuable in predicting pCR after NAC in breast cancer. APTWI combined with HER2 expression status can further enhance the predictive efficacy.