Objective:To explore the safety and efficacy of intraosseous regional administration (IORA) of vancomycin for preventing infection in primary total knee arthroplasty (TKA).Methods:A total of 124 patients with knee osteoarthritis undergoing TKA between February 2024 and May 2024 at nine hospitals were enrolled. Preoperative infection prophylaxis involved either IORA (0.5 g vancomycin administered via intraosseous regional infusion before incision) or intravenous infusion (1 g vancomycin via peripheral vein). The IORA group included 15 males and 47 females with a median age of 66.5 years (range, 60.0-70.0 years), while the intravenous group included 14 males and 48 females with a median age of 66.0 years (range, 61.8-70.3 years) years. Intraoperative samples were collected including fat and synovium tissues after incision, before prosthesis placement, and after tourniquet release; distal femoral cancellous bone during femoral osteotomy; proximal tibial cancellous bone during tibial osteotomy; proximal intercondylar cancellous bone before prosthesis placement; and peripheral blood from non-infused arms at surgery initiation and after tourniquet release. Vancomycin concentrations were measured using liquid chromatography-tandem mass spectrometry. Vital sign changes were recorded from admission to 5~10 minutes post-IORA (IORA group) or post-incision (intravenous group). Follow-ups were conducted on postoperative day 1 and 3, and at 1 and 3 months, to document complications including IORA-related adverse events, periprosthetic joint infections, surgical site infections, red man syndrome, acute kidney injury, deep vein thrombosis and so on.Results:Vancomycin concentrations in bone, fat, and synovial tissue samples were significantly higher in the IORA group than in the intravenous group ( P<0.05), while vancomycin concentrations in blood samples were significantly lower in the IORA group than in the intravenous group ( P<0.05). Only 7.3%(41/558) of tissue samples in the IORA group had vancomycin concentrations below 2.0 μg/g (the minimum inhibitory concentration of vancomycin against coagulase-negative staphylococcus), compared to 59.3%(331/558) in the intravenous group (χ 2=11.285, P<0.001). In the intravenous group, 16.9%(21/124) of blood samples had vancomycin concentrations exceeding 15.0 mg/L (the threshold associated with a significantly increased risk of nephrotoxicity), while all concentrations in the IORA group were below this threshold, the difference was statistically significant (χ 2=22.943, P<0.001). There were no statistically significant difference ( P>0.05) in vital signs changes before and after vancomycin administration between the two groups. Two patients in the intravenous group experienced incision exudate, while no other related complications occurred in either group. Conclusions:Compared to the traditional intravenous infusion of 1 g vancomycin, intraosseous injection of a low dose (0.5 g) of vancomycin achieves higher local tissue concentrations in the knee joint with a lower incidence of adverse reactions and is safe for infection prophylaxis. Despite guidelines not recommending the routine use of vancomycin for preventing infection after primary TKA, intraosseous injection of 0.5 g vancomycin may be considered intraoperatively for primary TKA in the following scenarios: patients in medical institutions with a high prevalence of methicillin-resistant staphylococcus aureus (MRSA) infections, patients with potential preoperative MRSA colonization, or patients with cephalosporin allergy.

BACKGROUND: Fibrosis of the connective tissue in the vaginal wall predominates in pelvic organ prolapse (POP), which is characterized by excessive fibroblast-to-myofibroblast differentiation and abnormal deposition of the extracellular matrix (ECM). Our study aimed to investigate the effect of ECM stiffness on vaginal fibroblasts and to explore the role of methyltransferase 3 (METTL3) in the development of POP. METHODS: Polyacrylamide hydrogels were applied to create an ECM microenvironment with variable stiffness to evaluate the effects of ECM stiffness on the proliferation, differentiation, and expression of ECM components in vaginal fibroblasts. METTL3 small interfering RNA and an overexpression vector were transfected into vaginal fibroblasts to evaluate the effects of METTL3 silencing and overexpression on matrix stiffness-induced vaginal fibroblast-to-myofibroblast differentiation and abnormal modulation of the ECM. Both procedures were detected by 5-ethynyl-2'-deoxyuridine (EdU) staining, Western blotting (WB), quantitative real-time polymerase chain reaction (RT-qPCR), and immunofluorescence (IF). RESULTS: Vaginal fibroblasts from POP patients exhibited increased proliferation ability, increased expression of α-smooth muscle actin (α-SMA), decreased expression of collagen I/III, and significantly decreased expression of tissue inhibitors of matrix metalloproteinases (TIMPs) in the stiff matrix ( P <0.05). Compared with those from non-POP patients, vaginal wall tissues from POP patients demonstrated a significant increase in METTL3 content ( P <0.05). However, silencing METTL3 expression in vaginal fibroblasts with high ECM stiffness resulted in decreased proliferation ability, decreased α-SMA expression, an increased ratio of collagen I/III, and increased TIMP1 and TIMP2 expression. Conversely, METTL3 overexpression significantly promoted the process of increased proliferation ability, increased α-SMA expression, decreased ratio of collagen I/III and decreased TIMP1 and TIMP2 expression in the soft matrix ( P <0.05). CONCLUSIONS Elevated ECM stiffness can promote excessive proliferation, differentiation, and abnormal ECM modulation, and the expression of METTL3 plays an important role in alleviating or aggravating matrix stiffness-induced vaginal fibroblast-to-myofibroblast differentiation and abnormal ECM modulation.
Humans ; Female ; Extracellular Matrix/metabolism* ; Cell Differentiation/genetics* ; Methyltransferases/metabolism* ; Pelvic Organ Prolapse/pathology* ; Fibroblasts/metabolism* ; Myofibroblasts/metabolism* ; Vagina/metabolism* ; Cell Proliferation/physiology* ; Cells, Cultured ; Middle Aged

Objective:To explore the safety and efficacy of intraosseous regional administration (IORA) of vancomycin for preventing infection in primary total knee arthroplasty (TKA).Methods:A total of 124 patients with knee osteoarthritis undergoing TKA between February 2024 and May 2024 at nine hospitals were enrolled. Preoperative infection prophylaxis involved either IORA (0.5 g vancomycin administered via intraosseous regional infusion before incision) or intravenous infusion (1 g vancomycin via peripheral vein). The IORA group included 15 males and 47 females with a median age of 66.5 years (range, 60.0-70.0 years), while the intravenous group included 14 males and 48 females with a median age of 66.0 years (range, 61.8-70.3 years) years. Intraoperative samples were collected including fat and synovium tissues after incision, before prosthesis placement, and after tourniquet release; distal femoral cancellous bone during femoral osteotomy; proximal tibial cancellous bone during tibial osteotomy; proximal intercondylar cancellous bone before prosthesis placement; and peripheral blood from non-infused arms at surgery initiation and after tourniquet release. Vancomycin concentrations were measured using liquid chromatography-tandem mass spectrometry. Vital sign changes were recorded from admission to 5~10 minutes post-IORA (IORA group) or post-incision (intravenous group). Follow-ups were conducted on postoperative day 1 and 3, and at 1 and 3 months, to document complications including IORA-related adverse events, periprosthetic joint infections, surgical site infections, red man syndrome, acute kidney injury, deep vein thrombosis and so on.Results:Vancomycin concentrations in bone, fat, and synovial tissue samples were significantly higher in the IORA group than in the intravenous group ( P<0.05), while vancomycin concentrations in blood samples were significantly lower in the IORA group than in the intravenous group ( P<0.05). Only 7.3%(41/558) of tissue samples in the IORA group had vancomycin concentrations below 2.0 μg/g (the minimum inhibitory concentration of vancomycin against coagulase-negative staphylococcus), compared to 59.3%(331/558) in the intravenous group (χ 2=11.285, P<0.001). In the intravenous group, 16.9%(21/124) of blood samples had vancomycin concentrations exceeding 15.0 mg/L (the threshold associated with a significantly increased risk of nephrotoxicity), while all concentrations in the IORA group were below this threshold, the difference was statistically significant (χ 2=22.943, P<0.001). There were no statistically significant difference ( P>0.05) in vital signs changes before and after vancomycin administration between the two groups. Two patients in the intravenous group experienced incision exudate, while no other related complications occurred in either group. Conclusions:Compared to the traditional intravenous infusion of 1 g vancomycin, intraosseous injection of a low dose (0.5 g) of vancomycin achieves higher local tissue concentrations in the knee joint with a lower incidence of adverse reactions and is safe for infection prophylaxis. Despite guidelines not recommending the routine use of vancomycin for preventing infection after primary TKA, intraosseous injection of 0.5 g vancomycin may be considered intraoperatively for primary TKA in the following scenarios: patients in medical institutions with a high prevalence of methicillin-resistant staphylococcus aureus (MRSA) infections, patients with potential preoperative MRSA colonization, or patients with cephalosporin allergy.

Objective Establish a standardized evaluation system for medical faults,and provide theoretical basis for medical institutions and related industries to evaluate the illegality of medical behaviors.Methods Based on a litera-ture review,the medical fault assessment system was initially constructed,and then a research group was estab-lished to use Delphi method to invite 31 experts to evaluate the importance and feasibility of each article of the medi-cal fault assessment system and put forward suggestions for modification.Results The effective recovery rates of the two rounds of expert consultation were 83.9％and 96.8％,the expert authority coefficient was 0.902 and 0.887,and the Kendall's W test of all levels differences were statistically significant(P＜0.001).The medical fault assess-ment system finally constructed includes 5 first-level items including practicing medicine according to law,informed notification,diagnosis and treatment technology,medical record documents and hospital management,as well as 10 second-level items,20 third-level items and 47 fourth-level items.The mean values of importance and feasibili-ty scores of all articles were greater than 4,standard deviations were less than 1,and coefficients of variation were less than 0.2.Conclusion The medical fault standardized evaluation system is scientific,reliable,innovative and appli-cable.

Objective Establish a standardized evaluation system for medical faults,and provide theoretical basis for medical institutions and related industries to evaluate the illegality of medical behaviors.Methods Based on a litera-ture review,the medical fault assessment system was initially constructed,and then a research group was estab-lished to use Delphi method to invite 31 experts to evaluate the importance and feasibility of each article of the medi-cal fault assessment system and put forward suggestions for modification.Results The effective recovery rates of the two rounds of expert consultation were 83.9％and 96.8％,the expert authority coefficient was 0.902 and 0.887,and the Kendall's W test of all levels differences were statistically significant(P＜0.001).The medical fault assess-ment system finally constructed includes 5 first-level items including practicing medicine according to law,informed notification,diagnosis and treatment technology,medical record documents and hospital management,as well as 10 second-level items,20 third-level items and 47 fourth-level items.The mean values of importance and feasibili-ty scores of all articles were greater than 4,standard deviations were less than 1,and coefficients of variation were less than 0.2.Conclusion The medical fault standardized evaluation system is scientific,reliable,innovative and appli-cable.

Objective Establish a standardized evaluation system for medical faults,and provide theoretical basis for medical institutions and related industries to evaluate the illegality of medical behaviors.Methods Based on a litera-ture review,the medical fault assessment system was initially constructed,and then a research group was estab-lished to use Delphi method to invite 31 experts to evaluate the importance and feasibility of each article of the medi-cal fault assessment system and put forward suggestions for modification.Results The effective recovery rates of the two rounds of expert consultation were 83.9％and 96.8％,the expert authority coefficient was 0.902 and 0.887,and the Kendall's W test of all levels differences were statistically significant(P＜0.001).The medical fault assess-ment system finally constructed includes 5 first-level items including practicing medicine according to law,informed notification,diagnosis and treatment technology,medical record documents and hospital management,as well as 10 second-level items,20 third-level items and 47 fourth-level items.The mean values of importance and feasibili-ty scores of all articles were greater than 4,standard deviations were less than 1,and coefficients of variation were less than 0.2.Conclusion The medical fault standardized evaluation system is scientific,reliable,innovative and appli-cable.

Objective Establish a standardized evaluation system for medical faults,and provide theoretical basis for medical institutions and related industries to evaluate the illegality of medical behaviors.Methods Based on a litera-ture review,the medical fault assessment system was initially constructed,and then a research group was estab-lished to use Delphi method to invite 31 experts to evaluate the importance and feasibility of each article of the medi-cal fault assessment system and put forward suggestions for modification.Results The effective recovery rates of the two rounds of expert consultation were 83.9％and 96.8％,the expert authority coefficient was 0.902 and 0.887,and the Kendall's W test of all levels differences were statistically significant(P＜0.001).The medical fault assess-ment system finally constructed includes 5 first-level items including practicing medicine according to law,informed notification,diagnosis and treatment technology,medical record documents and hospital management,as well as 10 second-level items,20 third-level items and 47 fourth-level items.The mean values of importance and feasibili-ty scores of all articles were greater than 4,standard deviations were less than 1,and coefficients of variation were less than 0.2.Conclusion The medical fault standardized evaluation system is scientific,reliable,innovative and appli-cable.

Objective Establish a standardized evaluation system for medical faults,and provide theoretical basis for medical institutions and related industries to evaluate the illegality of medical behaviors.Methods Based on a litera-ture review,the medical fault assessment system was initially constructed,and then a research group was estab-lished to use Delphi method to invite 31 experts to evaluate the importance and feasibility of each article of the medi-cal fault assessment system and put forward suggestions for modification.Results The effective recovery rates of the two rounds of expert consultation were 83.9％and 96.8％,the expert authority coefficient was 0.902 and 0.887,and the Kendall's W test of all levels differences were statistically significant(P＜0.001).The medical fault assess-ment system finally constructed includes 5 first-level items including practicing medicine according to law,informed notification,diagnosis and treatment technology,medical record documents and hospital management,as well as 10 second-level items,20 third-level items and 47 fourth-level items.The mean values of importance and feasibili-ty scores of all articles were greater than 4,standard deviations were less than 1,and coefficients of variation were less than 0.2.Conclusion The medical fault standardized evaluation system is scientific,reliable,innovative and appli-cable.

Objective Establish a standardized evaluation system for medical faults,and provide theoretical basis for medical institutions and related industries to evaluate the illegality of medical behaviors.Methods Based on a litera-ture review,the medical fault assessment system was initially constructed,and then a research group was estab-lished to use Delphi method to invite 31 experts to evaluate the importance and feasibility of each article of the medi-cal fault assessment system and put forward suggestions for modification.Results The effective recovery rates of the two rounds of expert consultation were 83.9％and 96.8％,the expert authority coefficient was 0.902 and 0.887,and the Kendall's W test of all levels differences were statistically significant(P＜0.001).The medical fault assess-ment system finally constructed includes 5 first-level items including practicing medicine according to law,informed notification,diagnosis and treatment technology,medical record documents and hospital management,as well as 10 second-level items,20 third-level items and 47 fourth-level items.The mean values of importance and feasibili-ty scores of all articles were greater than 4,standard deviations were less than 1,and coefficients of variation were less than 0.2.Conclusion The medical fault standardized evaluation system is scientific,reliable,innovative and appli-cable.

Objective To investigate the main dietary patterns of children in urban areas of Maanshan City, and to explore the association between dietary patterns and subthreshold autism trait (SAT), attention-deficit/hyperactivity disorder (ADHD) symptoms and comorbid behaviors in 3-year-old children. Methods Based on the birth cohort of Maanshan Maternal and Infant Health from June 2015 to June 2016，regular physical examinations were conducted from 4 to 2 to 1, and follow-up was conducted until the age of 3. A semi-quantitative food frequency questionnaire was employed to assess dietary intakes. SAT and ADHD symptoms were assessed by Clancy autism behavior scale (CABS) and the 10-item Chinese version of the Conners Abbreviated Symptom Questionnaire (C-ASQ). Social-demographic information was also collected. Results The detection rates of SAT, ADHD symptoms, and comorbidity were 11.03%, 5.28%, and 2.71%, respectively. The older the father, the higher the mother's education level, and the higher the per capita monthly income of the family, the lower the SAT detection rate (P<0.05). The higher the father's educational level, the lower the detection rate of ADHD symptoms (P<0.05). The older the mother and the higher the education level, the lower the detection rate of comorbid behavior in their children (P <0.05). After adjusting for demographic influencing factors, the low intake level was used as a reference. The vegetarian type with moderate intake level was negatively correlated with SAT, while the processed food type with high intake level was positively correlated with SAT. The vegetarian type with high intake level was negatively correlated with ADHD symptoms, while the snack type with high intake level was positively correlated with ADHD symptoms. The vegetarian type with high intake level was negatively correlated with comorbidity. Conclusion Unhealthy dietary patterns are related to children's SAT and ADHD symptoms. Correcting children's unhealthy eating patterns may help reduce children's behavior problems.