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 investigate the therapeutic efficacy of cinnamaldehyde (CA) on systemic Candida albicans infection in mice and to provide supportive data for the development of novel antifungal drugs. METHODS: Ninety BALB/c mice were randomly divided into 3 groups according to a random number table: CA treatment group, fluconazole (positive control) group, and Tween saline (negative control) group, with 30 mice in each group. Initially, all groups of mice received consecutive intraperitoneal injections of cyclophosphamide at 200 mg/kg for 2 days, followed by intraperitoneal injection of 0.25 mL C. albicans fungal suspension (concentration of 1.0 × 10⁷ CFU/mL) on the 4th day, to establish an immunosuppressed systemic Candida albicans infection animal model. Subsequently, the mice were orally administered CA, fluconazole and Tween saline, at 240, 240 mg/kg and 0.25 mL/kg respectively for 14 days. After a 48-h discontinuation of treatment, the liver, small intestine, and kidney tissues of mice were collected for fungal direct microscopic examination, culture, and histopathological examination. Additionally, renal tissues from each group of mice were collected for (1,3)- β -D-glucan detection. The survival status of mice in all groups was monitored for 14 days of drug administration. RESULTS: The CA group exhibited a fungal clearance rate of C. albicans above 86.7% (26/30), significantly higher than the fluconazole group (60.0%, 18/30, P<0.01) and the Tween saline group (30.0%, 9/30, P<0.01). Furthermore, histopathological examination in the CA group revealed the disappearance of inflammatory cells and near-normal restoration of tissue structure. The (1,3)-β-D-glucan detection value in the CA group (860.55 ± 126.73 pg/mL) was significantly lower than that in the fluconazole group (1985.13 ± 203.56 pg/mL, P<0.01) and the Tween saline group (5910.20 ± 320.56 pg/mL, P<0.01). The mouse survival rate reached 90.0% (27/30), higher than the fluconazole group (60.0%, 18/30) and the Tween saline group (30.0%, 9/30), with a significant difference between the two groups (both P<0.01). CONCLUSIONS CA treatment exhibited significant therapeutic efficacy in mice with systemic C. albicans infection. Therefore, CA holds potential as a novel antifungal agent for targeted treatment of C. albicans infection.
Animals ; Acrolein/pharmacology* ; Candida albicans/physiology* ; Mice, Inbred BALB C ; Candidiasis/pathology* ; Antifungal Agents/therapeutic use* ; Mice ; Fluconazole/therapeutic use* ; Kidney/drug effects* ; Female

Objective To analyze the preferences of elderly cancer patients for internet hospital diagnosis and treatment services,providing a reference for the sustainable development of internet hospitals.Methods This study was based on the method of discrete choice experiments.By combining literature review and expert consultation,10 relevant attributes affecting the choice of internet hospitals by elderly cancer patients were determined.Through KANO questionnaires,6 key attributes were se-lected to form the final DCE questionnaire,consisting of 11 choice sets and 1"quality control"set.Using the convenience sam-pling method,elderly cancer patients visiting a certain tertiary hospital in Tianjin were selected to collect 318 valid question-naires.The obtained data were analyzed using mixed Logit regression.Results Patients visiting a certain specialized cancer hos-pital in Tianjin tend to prefer hospitals with a grade of Grade Ⅲ-A(β=0.661 6,P＜0.05)and those offering out-of-hospital rehabilitation guidance for cancer patients(β=0.559 9,P＜0.05).The page operation process(β=0.352 2,P＜0.05)and the accessibility mode for the elderly(β=0.357 5,P＜0.05)are the attributes with lower attention.In the subgroup analysis,for patients of different genders and different family incomes,hospital grade and out-of-hospital rehabilitation guidance for cancer patients remain the most influential factors,but male patients pay more attention to the page operation process(β=0.378 3,P＜0.05)and the accessibility mode for the elderly(β=0.373 7,P＜0.05),while female patients pay more attention to the cover-age of medical insurance reimbursement(β=0.435 9,P＜0.05),which has a greater impact than that of male patients(β=0.394 7,P＜0.05);patients with a monthly per capita income of less than 5 000 yuan pay more attention to the coverage of medical insurance reimbursement(β=0.423 0,P＜0.05)and the self-appointment check function(β=0.467 0,P＜0.05);while patients with a monthly per capita income of more than 5 000 yuan pay more attention to the page operation process(β=0.364 7,P＜0.05)and the accessibility mode for the elderly(β=0.359 1,P＜0.05).Conclusion Hospitals should en-hance elderly patients' awareness and trust in internet hospitals by providing comprehensive health education and support,simpli-fying operational processes,strengthening age-friendly design,and highlighting medical insurance coverage to address the diverse needs across genders and income levels.

Objective To analyze the preferences of elderly cancer patients for internet hospital diagnosis and treatment services,providing a reference for the sustainable development of internet hospitals.Methods This study was based on the method of discrete choice experiments.By combining literature review and expert consultation,10 relevant attributes affecting the choice of internet hospitals by elderly cancer patients were determined.Through KANO questionnaires,6 key attributes were se-lected to form the final DCE questionnaire,consisting of 11 choice sets and 1"quality control"set.Using the convenience sam-pling method,elderly cancer patients visiting a certain tertiary hospital in Tianjin were selected to collect 318 valid question-naires.The obtained data were analyzed using mixed Logit regression.Results Patients visiting a certain specialized cancer hos-pital in Tianjin tend to prefer hospitals with a grade of Grade Ⅲ-A(β=0.661 6,P＜0.05)and those offering out-of-hospital rehabilitation guidance for cancer patients(β=0.559 9,P＜0.05).The page operation process(β=0.352 2,P＜0.05)and the accessibility mode for the elderly(β=0.357 5,P＜0.05)are the attributes with lower attention.In the subgroup analysis,for patients of different genders and different family incomes,hospital grade and out-of-hospital rehabilitation guidance for cancer patients remain the most influential factors,but male patients pay more attention to the page operation process(β=0.378 3,P＜0.05)and the accessibility mode for the elderly(β=0.373 7,P＜0.05),while female patients pay more attention to the cover-age of medical insurance reimbursement(β=0.435 9,P＜0.05),which has a greater impact than that of male patients(β=0.394 7,P＜0.05);patients with a monthly per capita income of less than 5 000 yuan pay more attention to the coverage of medical insurance reimbursement(β=0.423 0,P＜0.05)and the self-appointment check function(β=0.467 0,P＜0.05);while patients with a monthly per capita income of more than 5 000 yuan pay more attention to the page operation process(β=0.364 7,P＜0.05)and the accessibility mode for the elderly(β=0.359 1,P＜0.05).Conclusion Hospitals should en-hance elderly patients' awareness and trust in internet hospitals by providing comprehensive health education and support,simpli-fying operational processes,strengthening age-friendly design,and highlighting medical insurance coverage to address the diverse needs across genders and income levels.

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 evaluate the efficacy and safety of first-line anti-tuberculosis (TB) drugs combined with linezolid in treatment of children with tuberculous meningitis (TBM).Methods:A retrospective cohort study design was performed . Eight-nine Children diagnosed as TBM during January 1 st 2016 and December 31 st 2023 in Department of Infectious Disease, Children′s Hospital of Chongqing Medical University were enrolled in the study. According to different treatment regimens, children were divided into a group of first-line anti-tuberculous drugs (isoniazid, rifampicin, pyrazinamide, ethambutol (HRZE)) and a group of HRZE and linezolid combination (HRZEL). The efficacy and safety of the 2 regimens were compared and the relationship between linezolid drug concentration and adverse reactions were analyzed. Comparisons between groups were performed using χ2 test and Mann-Whitney U test. Results:The 89 children with TBM included 53 males and 36 females with an onset age of 4.6 (1.4, 9.6) years. There were 27 cases in the HZREL group and 62 cases in the HRZE group. Before treatment, positive rate of interferon-gamma release assays (IGRA) in HRZEL group was lower than that in HRZE group (64% (16/25) vs.92% (55/60), χ2=9.82, P<0.05), but protein level of cerebrospinal fluid (CSF) was higher than that in HRZE group (1.2 (1.0, 2.0) vs.0.8 (0.4,1.4) g/L, Z=0.32, P<0.05). By the end of the intensive phase, there were no significant differences of rates of CSF improvement and etiology negativity between HRZEL group and HRZE group (both P>0.05).The 44 TBM children with high CSF protein (>1 g/L) included 25 males and 19 females with an onset age of 6.7 (3.0, 11.8) years. There were 21 cases in the HZREL group and 23 cases in the HRZE group accordingly. Before treatment, there were no significant differences of positive rate of IGRA test and CSF protein level between the 2 groups (62% (13/21) vs. 87% (20/23), 1.7 (1.1, 2.2) vs. 1.5 (1.2, 1.9) g/L, χ2=3.67, Z=0.23, both P>0.05). There were no significant differences in CSF indicators, etiology negativity or imaging remission between the two groups by the end of intensive phase (all P>0.05). Higher frequencies of granulocytopenia, gastrointestinal symptoms as well as withdrawal or change of drugs were found in HRZEL group when compared to those in HRZE group (44% (12/27) vs. 19% (12/62), 7% (2/27) vs. 0, 33% (9/27) vs. 3% (2/62), χ2=6.01, 4.70, 15.74, all P<0.05). Conclusions:The efficacy of HRZEL regimen is similar to conventional HRZE regimen in children with TBM, but with higher adverse effect. Prudentially evaluating the pros and cons of linezolid in the usage of drug-susceptible TB and carefully monitoring of linezolid associated adverse effects is suggested.

Objective:To investigate the possible role of miR-146a in the patho-genesis of inflammation in primary gout arthritis.Methods:① The RAW264.7 mouse macrophage was stimulated with 200 μg/ml monosodium urate (MSU) crystal for 0 h, 3 h, 6 h, and 12 h. Then cells and super-natants were collected. The miR-146a was detected by TaqMan probe method. The expression of interleukin-1 receptor-associated kinase 1 (IRAK 1), tumor necrosis factor receptor-associated factor 6 (TRAF6), nuclear factor-kappa B (NF-κB), interleukin (IL)-1β, tumor necrosis factor-α (TNF-α) mRNA were detected by real-time (RT)-quantitative polymerase chain reaction (qPCR). The concentration of IL-1β was measured in the culture supernatant by enzyme-linked immunosorbent assay (ELISA). The protein expression levels of TRAF6, NF-κB and IL-1β were detected by Western-blotting. ② The RAW264.7 mouse macrophage was transfected with miR-146a mimics, miR-146a mimic control, miR-146a inhibitor, and miR-146a inhibitor control. After stimulating each group of cells with 200 μg/ml MSU crystals for 6 h, the expression of miR-146a, IRAK1, TRAF6, NF-κB, IL-1β mRNA and TRAF6, NF-κB, IL-1β protein were measured. The measurement data were compared by Independent sample t test. and repeated measures analysis of variance (ANOVA). Results:① After MSU crystals stimulated RAW264.7 cells, we found that the expression level of miR-146a in the stimulation group at 3 h, 6 h, and 12 h was lower than that in the control group ( t=-10.234, -17.059, -26.204, P<0.01), and then, IL-1β protein concentration at 6 h, 12 h was higher ( t=7.552, 9.007, P<0.01). Meanwhile, IRAK1, TRAF6, NF-κB and IL-1β mRNA in the stimulation group at 3 h and 6 h were higher than those in the control group ( t=9.847, 6.147, P<0.01; t=3.49, 3.32, P<0.05; t=3.643, 8.471, P<0.05; t=8.726, 49.68, P<0.01). TNF-α mRNA at three time points in the stimulation group was high ( t=4.691, 11.115, 12.816, P<0.01). Moreover, the results showed that the relative expression of TRAF6 and NF-κB protein in the stimulation group at 6 h and 12 h was higher than that in the control group ( t=8.052, 8.119, P<0.01, t=22.454, 5.845, P<0.01), IL-1β protein in the stimulation group increased at all three time points compared with the control group ( t=18.561, 4.74, 8.432, P<0.01). ② After trans fection, the miR-146a mRNA expression of the mimics group was significantly higher than the mimics control group ( t=31.769, P<0.01); the inhibitor group was significantly lower than the inhibitor control group ( t=-4.22, P<0.05). ③miR -146a overexpression group was stimulated with 200 μg/ml MSU crystals for6 h, the expression levels of IRAK 1, TRAF 6, NF-κB and IL-1β mRNA in the mimic group were lower than those in the mimic control group ( t=-14.754, -21.201, -19.381, -17.323, P<0.01), the expression levels of TRAF 6, NF-κB and IL-1β protein were also lower than those in the mimic control group ( t=-3.137, -32.974, -18.789, P<0.05), while the inhibitor group had good results. Conclusion:① Overexpression of miR-146a can reduce the expression of IRAK1, TRAF6, NF-κB, IL-1β and inhibit MSU crystal-mediated inflammation, while inhibition of miR-146a expression can aggravate inflammation, suggesting that miR-146a participates in the negative feedback regulation of gout inflammation. ② miR-146a may target the NF-κB signaling pathway and participate in spontaneous remission of gouty arthritis.

Objective:To evaluate the role of hypoxia-inducible factor-1α (HIF-1α) in hydrogen-induced inhibition of lipopolysaccharide (LPS)-induced inflammatory responses in mouse macrophages.Methods:The mouse RAW264.7 macrophages cultured in vitro were divided into 4 groups ( n=24 each) according to the random number table method: control group (C group), LPS group (L group), hydrogen-rich solution plus LPS group (H+ L group), and hydrogen-rich solution plus LPS plus HIF-1α inhibitor 2-methoxyestradiol (2ME2) group (H+ L+ M group). LPS 1 μg/ml was added, and the cells were incubated for 6 h in group L. In group L+ H, LPS was added first, the medium was changed to 0.6 mmol/L hydrogen-rich solution, and cells were incubated for 6 h. In group H+ L+ M, 2ME2 10 μmol/L was given first, cells were then incubated for 30 min, LPS and hydrogen-rich solution were added, and cells were incubated for 6 h. Western blot was used to determine the expression of HIF-1α, Beclin-1, Bcl-2/E1B-19 kDa interacting protein 3 (BNIP3) and LC3.Enzyme-linked immunosorbent assay was used to detect the concentrations of tumor necrosis factor (TNF)-α, interleukin (IL)-6, and IL-1β in the supernatant.The number of autophagosomes was observed using a transmission electron microscope. Results:Compared with group C, the concentrations of TNF-α, IL-6 and IL-1β in the supernatant were significantly increased, the expression of HIF-1α, Beclinl and BNIP3 in macrophages was up-regulated, the ratio of LC3Ⅱ/LC3Ⅰ was increased, and the number of autophagosomes was increased in group L ( P<0.05). Compared with group L, the concentrations of TNF-α, IL-6 and IL-1β were significantly decreased, the expression of HIF-1α, Beclin-1 and BNIP3 in macrophages was up-regulated, LC3Ⅱ/LC3Ⅰ ratio was increased, and the number of autophagosomes was increased in group H+ L ( P<0.05). Compared with group H+ L, the concentrations of TNF-α, IL-6 and IL-1β in the supernatant were significantly decreased, the expression of HIF-1α, Beclin-1, and BNIP3 in macrophages was down-regulated, and the ratio of LC3Ⅱ/LC3Ⅰ was decreased, and the number of autophagosomes was decreased in group H+ L+ M ( P<0.05). Conclusion:HIF-1α-mediated activation of autophagy is involved in the process of hydrogen-induced inhibition of LPS-induced inflammatory responses in mouse macrophages.

Objective:To investigate the clinical effect of minimally invasive surgery in the treatment of professional drivers with lumbar disc herniation.Methods:126 patients with lumbar disc herniation admitted to hospital from June 1, 2015 to December 30, 2018 were selected and divided into observation group (59 cases treated by percutaneous transforaminal endoscopy) and control group (67 cases treated with conventional conservative treatment) according to the treatment methods. The Visual Analogue Scale (VAS) and Japanese Orthopaedic Association Scores (JOA) before and after treatment were analyzed retrospectively. Length of stay, time out of bed, hospitalization expenses and recurrence rate were evaluated. The measurement data was expressed by ± s, the comparison between groups was performed by t test, and the count data were analyzed by descriptive analysis. Results:Before treatment, there was no significant difference in gender, age, VAS score and JOA score between the two groups ( P>0.05) . After treatment, compared with the control group, the VAS score of the observation group was lower, the JOA score was higher, the time out of bed was shorter, the average hospitalization time was reduced, the average hospitalization cost was higher, and the recurrence rates after Six months and one year were lower in the observation group, the differences were statistically significant ( P<0.05) . Conclusion:The clinical effect of percutaneous transforaminal endoscopic treatment is better than that of conventional conservative treatment for driver＇s lumbar disc herniation.

Objective:To investigate the clinical effect of minimally invasive surgery in the treatment of professional drivers with lumbar disc herniation.Methods:126 patients with lumbar disc herniation admitted to hospital from June 1, 2015 to December 30, 2018 were selected and divided into observation group (59 cases treated by percutaneous transforaminal endoscopy) and control group (67 cases treated with conventional conservative treatment) according to the treatment methods. The Visual Analogue Scale (VAS) and Japanese Orthopaedic Association Scores (JOA) before and after treatment were analyzed retrospectively. Length of stay, time out of bed, hospitalization expenses and recurrence rate were evaluated. The measurement data was expressed by ± s, the comparison between groups was performed by t test, and the count data were analyzed by descriptive analysis. Results:Before treatment, there was no significant difference in gender, age, VAS score and JOA score between the two groups ( P>0.05) . After treatment, compared with the control group, the VAS score of the observation group was lower, the JOA score was higher, the time out of bed was shorter, the average hospitalization time was reduced, the average hospitalization cost was higher, and the recurrence rates after Six months and one year were lower in the observation group, the differences were statistically significant ( P<0.05) . Conclusion:The clinical effect of percutaneous transforaminal endoscopic treatment is better than that of conventional conservative treatment for driver＇s lumbar disc herniation.