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.

Patients with metastatic castration-resistant prostate cancer (mCRPC) face poor prognoses due to tumor heterogeneity and drug resistance. Antibody-drug conjugates (ADCs) have been under development for over two decades for mCRPC treatment. Several clinical trials have demonstrated promising antitumor activity and acceptable safety profiles for ADCs in this setting. Among prostate-specific membrane antigen (PSMA)-targeted ADCs, ARX517 demonstrates superior safety and more significant prostate-specific antigen (PSA) reductions compared to earlier agents such as MLN2704, PSMA-ADC, and MEDI3726. ADCs targeting B7-H3, such as MGC018 and DB-1311, have also shown antitumor activity. ADCs targeting other antigens, including six-transmembrane epithelial antigen of the prostate (STEAP)1 (DSTP3086S), trophoblast cell surface antigen (TROP)2 (sacituzumab govitecan), and solute carrier (SLC) 44A4 (ASG-5ME), have shown preliminary antitumor activity in early trials but face challenges with insufficient efficacy or toxicity. Tisotumab vedotin (targeting tissue factor) has shown no significant therapeutic response in mCRPC. Meanwhile, disitamab vedotin (HER2-targeted), ABBV-969 and DXC008 (both dual PSMA/STEAP1-targeted) are currently under evaluation. Notably, an international multicenter phase Ⅲ clinical trial (NCT06925737) for mCRPC has been initiated in May 2025 for evaluating B7-H3-targeted ADC ifinatamab deruxtecan. This review summarizes recent advances in ADCs targeting key antigens in mCRPC (including PSMA, B7-H3, STEAP1, TROP2, SLC44A4, and others) and explores combination strategies, offering insights to inform the clinical management of mCRPC.
Humans ; Prostatic Neoplasms, Castration-Resistant/pathology* ; Male ; Immunoconjugates/therapeutic use* ; Glutamate Carboxypeptidase II/immunology* ; Antibodies, Monoclonal, Humanized/therapeutic use* ; B7 Antigens/immunology* ; Neoplasm Metastasis ; Prostate-Specific Antigen ; Antigens, Neoplasm/immunology* ; Antigens, Surface ; Camptothecin/analogs & derivatives* ; Oxidoreductases

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:To explore the effect of moderate-intensity swimming exercise on liver glucose and lipid metabolism disorder in type 2 diabetic rats and possible mechanism. Method:Eight-week-old male SD rats were randomly selected as a blank control group(negative control group,NC group)and fed with normal food,while the rest were fed with high-fat and high-sugar adaptively for one week.Streptozotocin(Streptozotocin,STZ,30mg/kg)was injected intraperitoneally to produce the T2DM rat model.Sixteen rats were randomly selected as type 2 diabetes model group(diabetic model group,DC group)and type 2 diabetes aerobic exercise group(diabetic swimming group,DS group),with eight rats in each group.Aerobic exercise was intervened by non-weight-bearing swimming.After 3 days of adaptive train-ing,the exercise time was 15min/day,and gradually increased to 60min/day,5 days/week,for a total of 8 weeks of training.During the experiment,the body weight,blood sugar,and liver index of rats in each group were detected;ELISA was used to detect the serum insulin(insulin),tumor necrosis factor-α(TNF-α),interleukin-6(IL-6),interleukin-1β(IL-1β),serum total cholesterol(TC),triglyceride(TG),low-density lipo-protein cholesterol(LDL-C),HDL Lipoprotein cholesterol(HDL-C)and serum alanine aminotransferase(ALT)and aspartate aminotransferase(AST)levels;the expression changes of peroxisome proliferator-activat-ed receptor γ(PPARγ),nuclear factor-κB(NF-κB)and adiponectin(ADPN)in liver tissue were detected. Result:After 8 weeks of aerobic exercise intervention,compared with the DC group,the rats in the DS group had significantly increased body weight,signifiicantly decreased blood sugar(P＜0.01),and significantly increased serum insulin and HDL-C levels(P＜0.01).The serum TNF-α,IL-6,IL-1β and TC,TG,LDL-C,ALT,AST levels were significantly decreased(P＜0.05 or P＜0.01).The liver index and oil red O staining pos-itive area decreased significantly(P＜0.01).The positive area of liver glycogen staining increased significantly(P＜0.01),with neatly arranged liver tissue cells and alleviated fat vacuoles,lipid droplets and inflammatory cell infiltration.The protein and mRNA expression levels of PPARγ,GLUT4 and ADPN in the liver were sig-nificantly increased(P＜0.05 or P＜0.01),and the levels of PPARγ and ADPN immunofluorescence positive cells were significantly increased(P＜0.01).The levels of mRNA and immunofluorescence positive cells of NF-κB were significantly decreased(P＜0.05 or P＜0.01).The mRNA level of ADIPOR2 was also significantly in-creased(P＜0.05),and the protein levels of NF-κB and IL-6 were significantly decreased(P＜0.01). Conclusion:8-week moderate-intensity swimming exercise can improve the disturbance of glucose and lipid me-tabolism by regulating the inflammatory response in the liver of T2DM rats,and the mechanism may be relat-ed to the PPARγ/NF-κB/ADPN pathway.

Objective To explore the technique and significance of intraoperative neuromonitoring (IONM) for scarless in the neck endoscopic thyroidectomy (SET) via breast approach.Methods From Apr.2015 to Oct.2015,101 consecutive patients undergoing SET with IONM were included.During the operation,patients received radical resection of the thyroid cancer by Wang's seven-step method.The lymph nodes in the central area were dissected and Wang's multi-functional separation forceps were implemented for recurrent laryngeal nerve (RLN) positioning,monitoring and protection.Also,time required for RLN positioning and exposure,postoperative transient and permanent RLN damage incidence were calculated to assess the feasibility of IONM under SET.Results Among 101 patients,130 RLNs in total were exposed.The average time required for RLN positioning under IONM was (3.26 ± 1.08)min,with round-nerve management time of (13.95 ± 4.58)min.Nerve signal change happened in 16.9％(22/130) patients.Positive predictive value was 13.6％ and negative predictive value was 100％.The overall accuracy rate was 85.4％.Conclusion IONM during SET is feasible,and can be helpful for the localization and functional protection of RLN and was useful to predict vocal cord paralysis.

Objective To investigate the effect of low sound pressure level infrasound on che-mokine-mediated inflammatory response in spinal cord in rats with neuropathic pain.Methods Seven-ty-two healthy male SD rats were randomly divided into sham operation group (group Sham),neuro-pathic pain group (group NP)and low sound pressure level infrasound intervention group (group LNP),24 in each.The sciatic nerve injury models were established.3 d after the model constructed, the rats in group LNP started to receive low sound pressure level infrasound therapy,4 h per day, continued for 21 d.1 d before surgery (T0 )and 3 d after surgery (T1 ),all rats were detected me-chanical paw withdrawal threshold (MWT).Respectively,after treated for 7 d (T2 ),14 d (T3 )and 21 d (T4 ),eight rats were randomly selected from each group and their MWT was measured.The ex-pressions of MCP-1 mRNA,CCR2 mRNA,TNF-αmRNA,IL-1βmRNA,and IL-6 mRNA in spinal cord in rats were detected using quantitative PCR,the expressions of MCP-1 protein and CCR2 protein in spinal cord in rats were detected by using Western blot.Results MWT in groups NP and LNP at T1-T4 was lower than that of group Sham,and that in group LNP at T3-T4 were higher than that of group NP,respectively (P <0.05).Compared with group Sham,the relative expression levels of MCP-1 mRNA,CCR2 mRNA,TNF-αmRNA,IL-1βmRNA,and IL-6 mRNA in spinal cord tis-sues in groups NP and LNP at T2-T4 were increased (P <0.05);compared with group NP,the rela-tive expression levels of MCP-1 mRNA,CCR2 mRNA,TNF-αmRNA,IL-1βmRNA,and IL-6 mR-NA in spinal cord were decreased in group LNP at T3-T4 (P <0.05 ).Western blot analysis showedthat the relative expression levels of MCP-1 protein and CCR2 proteinin spinal cord in groups NP and LNP at T2-T4 were higher than that of group Sham,while relative expression levels of MCP-1 protein and CCR2 proteinin spinal cord in group LNP at T3-T4 were lower than that of group NP. Conclusion The low sound pressure level infrasound could effectively reduce neuropathic pain in rats, possibly via inhibiting chemokine-mediated cascade inflammatory reaction.

Objective To investigate the effects of propofol on mesenteric artery in SD rats and to observe whether the effect of propofol on the mesenteric artery relaxation is related to the gap. Methods Pressure myograph was used to examine the effect of 18β-GA and 2-APB on the relaxation induced by propofol 1×10 -7 ,3×10 -7 ,1×10 -6 ,3×10 -6 ,1 ×10 -5 ,3 ×10 -5 ,1 ×10 -4 and 3 ×10 -4 mol/L in acutely separated mesenteric arterioles of SD rat.Results The diameter of mesenteric arteri-oles were increased from (208.6±13.4)to (213.5±13.6),(21 9.7±13.2),(226.4±12.5),(234.9 ±12.3),(245.5±13.0),(267.4±1 5.2),(336.2±18.3)and (385.9 ±14.2)μm after application of 1×10 -7 ,3×10 -7 ,1 × 10 -6 ,3 × 10 -6 ,1 × 10 -5 ,3 × 10 -5 ,1 × 10 -4 and 3 × 10 -4 mol/L propofol,re-spectively.Propofol induced dilation of the rat mesenteric arterioles in a concentration-dependent man-ner (P < 0.01 ).After pretreatment with 18β-GA and 2-APB,1 × 10 -4 mol/L propofol induced dilation was absolutely decreased (P <0.01).Conclusion These results suggest that propofol relaxes mesenteric arterioles via gap junction.

BACKGROUND:Due to different pathogenesis of degenerative and isthmic lumbar spondylolisthesis, the differences in sagittal spino-pelvic morphology and life quality between them are stil unclear.
OBJECTIVE:To investigate the differences in sagittal spino-pelvic morphology and life quality between degenerative and adult isthmic lumbar spondylolisis patients.
METHODS:From May 2012 to February 2015, 169 lumbar spondylolisthesis patients with complete imaging data were included in the study. Degenerative group contained 83 patients, and isthmic group contained 86 patients. The folowing radiographical parameters were measured on standard standing lateral radiographs of the entire spine, including thoracic kyphosis, lumbar lordosis, sagittal vertical axis, pelvic incidence, pelvic tilt and sacral slope. Meanwhile, slippage angle, slippage percentage and slippage distance ofal patients were also measured. SF-36 scale was employed to evaluate life quality, which was compared between groups.
RESULTS AND CONCLUSION:(1)Lumbar lordosis, thoracic kyphosis and slippage angle were significantly lower in the degenerative group than those in the isthmic group (P< 0.05-0.01). The sagittal vertical axis in degenerative group was higher than that in isthmic group (P< 0.01). (2) With respect to the domains of SF-36 scale, degenerative group had lower physical functioning score and social functioning score compared with the isthmic group (P< 0.01). (3) Pelvic incidence, pelvic tilt, sacral slope, slippage percentage and slippage distance showed no significant difference between two groups (P> 0.05). (4) Results suggested that pelvicmorphology between the degenerative and isthmic lumbar spondylolisthesis was similar. Compared with degenerative lumbar spondylolisthesis, isthmic spondylolisthesis patients have higher thoracic kyphosis, lumbar lordosis and slippage angle. In addition, notable limitations of physical functioning and social functioning were found in degenerative lumbar spondylolisthesis patients.

Objective:To observe the effect of electromyographic biofeedback on the wrist dirsiflexion function of the patients with cerebral infarction at different Brunnstrom stages, and to clarify the treatment of electromyographic biofeedback,and to provide basis for its clinical application.Methods:A total of 100 cerebral infarction patients were selected.Among them 54 BrunnstromⅠ-Ⅱ patients were randomly divided into treatment group (n= 32)and control group (n = 22),and another 46 Brunnstrom Ⅲ patients were randomly divided into treatment group (n=23)and control group (n=23).The patients in four groups were treated with the same routine stroke rehabilitation therapy while the patients in treatment groups still received the electromyographic biofeedback therapy additionally.The maximum electromyographic contraction of muscle,active range of movement (AROM) and Fugl-Meyers Assessment (FMA)of the extension of wrist joint were evaluated before treatment and 4 and 8 weeks after treatment,respectively.Results:The maximum electromyographic contraction values of muscle of the patients in BrunnstromⅠ-Ⅱ treatment group and control group were significantly improved 8 weeks after treatment (P <0.05),and the value in treatment group was higher than that in control group (P <0.05).The maximum electromyographic contraction value of muscle in Brunnstrom Ⅲ treatment group began to improve 4 weeks after treatment compared with before treatment (P < 0.05) and it was significantly higher than that in control group (P <0.05).The maximum electromyographic contraction value of muscle in Brunnstrom Ⅲ control group began to improve 8 weeks after treatment (P <0.05).The AROM in Brunnstrom Ⅰ-Ⅱ treatment group began to improve 8 weeks after treatment (P <0.05)and it was significantly higher than that in control group (P <0.05)while the AROM in control group had no significant change (P >0.05).The AROM in Brunnstrom Ⅲ treatment group and control group were significantly improved 4 weeks after treatment (P < 0.05 or P < 0.01 ), and the value in treatment group was significantly higher than that in control group (P < 0.05).The FMA in BrunnstromⅠ-Ⅱtreatment group and control group were significantly improved 8 weeks after treatment (P <0.05),while the value in treatment group was higher than that in control group (P <0.05);the FMA in Brunnstrom Ⅲ treatment group began to improve 4 weeks after treatment (P < 0.05)and it was significantly higher than that in control group (P <0.05). The FMA in control group began to improve 8 weeks after treatment (P <0.05). Conclusion:Electromyographic biofeedback can increase the strength and improve the body function of the patients with cerebral infaction.

BACKGROUND:Anatomic medul ary locking (AML) femoral prosthesis is circular cylinder and has satisfactory efficacy. However, some scholars found the complications such as thigh pain, loss of bone at the proximal end of the femur, and wearing-related osteolysis. F2L femoral prosthesis is cone-shaped and also has satisfactory efficacy, but the thigh pain incidence is relatively low. ＜br> OBJECTIVE:To compare the intermediate-long term results of AML versus F2L in total hip arthroplasty. ＜br> METHODS:Between November 1997 and January 2005, we retrospectively reviewed 60 patients (66 hips) undergoing total hip arthroplasty using biological femoral prosthesis. At fol ow-up examination, 58 hips in 52 patients were available for clinical and roentgenographic review. 26 AML devices were placed in 24 patients, and 32 F2L devices were placed in 28 patients. The AML group were reviewed with an average of 12.7 years fol ow-up (range 10 years and 3 months to 15 years and 5 months), while the F2L group were reviewed with an average of 9.5 years fol ow-up (range 8 years and 3 months to 11 years and 1 month). The clinical results were evaluated with Harris methods and X-ray examination. Kaplan-Meier analysis was performed to evaluate the survival of femoral component. End point was radiographical loosening or revision of the femoral component for any reason. ＜br> RESULTS AND CONCLUSION:There were no significant difference between AML and F2L about Harris score in the latest fol ow-up (P>0.05). After surgery, the incidence of thigh pain was significantly lower in F2L group than that in AML group (P＜0.05). In AMKL group, the stress-shielding 1 level was observed in 21 hips (81%), and 2 level in five hips (19%);in F2L group, the stress shielding 0 level was observed in 20 hips (62%) and 1 level in 12 hips (38%). There were significant differences between the two groups (P＜0.05). The stress shielding showed significant differences between the two groups (P＜0.05). The incidence of osteolysis in F2L group was significantly lower than that in AML group (P＜0.05). Kaplan-Meier analysis showed that, the survival rate of both AML and F2L components were 1.0 (95%confidence interval:0.98-1.00). Experimental findings indicate that, both AML and F2L femoral prosthesis have a satisfactory long-term efficacy after total hip arthroplasty, and the incidence of thigh pain and osteolysis is significantly lower in F2L group.