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.

Turning to critical illness is a common stage of various diseases and injuries before death. Patients usually have complex health conditions, while the treatment process involves a wide range of content, along with high requirements for doctor′s professionalism and multi-specialty teamwork, as well as a great demand for time-sensitive treatments. However, this is not matched with critical care professionals and the current state of medical care in China. Telemedicine, which shortens the distance of medical professionals and the gap of disease diagnosis and treatments in various regions through electronic information, can effectively solve the current problem. Therefore, there is an urgent need to develop a standardized, high-quality visualization telemedicine round system .Therefore, experts have been organized to search domestic and foreign literature on telemedicine round for critically ill patients and to form this consensus based on clinical experiences so as to further improve the level of critical care treatments in regions.

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.

Turning to critical illness is a common stage of various diseases and injuries before death. Patients usually have complex health conditions, while the treatment process involves a wide range of content, along with high requirements for doctor′s professionalism and multi-specialty teamwork, as well as a great demand for time-sensitive treatments. However, this is not matched with critical care professionals and the current state of medical care in China. Telemedicine, which shortens the distance of medical professionals and the gap of disease diagnosis and treatments in various regions through electronic information, can effectively solve the current problem. Therefore, there is an urgent need to develop a standardized, high-quality visualization telemedicine round system .Therefore, experts have been organized to search domestic and foreign literature on telemedicine round for critically ill patients and to form this consensus based on clinical experiences so as to further improve the level of critical care treatments in regions.

Objective To invesigate the feasibility of low radiation dose and low contrast dosage in triple-rule-out computed tomo-graphy angiography(TRO-CTA)on the 320-row detector CT.Methods A total of 120 patients who underwent CTA were prospec-tively selected.All patients were divided into control group(n=90)and experimental group(n=30).The control group employed standard-doses protocol of pulmonary CTA(120 kV tube voltage,45 mL contrast dosage),coronary CTA(120 kV,50-60 mL),and aortic CTA(120 kV,75 mL),while the experimental group received TRO-CTA with 100 kV and 70-80 mL.The peak time of contrast dosage at the pulmonary artery and aorta was measured by low-dose detection method in the experimental group,and the contrast examination was performed sequentially in the control group.Subjective scores and objective image quality of the pulmonary artery,coronary artery,and aorta in the experimental group and the control group were measured and compared,respectively.The effective dose(ED)between the two groups were recorded and compared.Independent samples t-test and Fisher exact probability were used to analyze the statistical differences between the above measures.Results There were no significant differences in CT values,con-trast-to-noise ratio(CNR),signal-to-noise ratio(SNR)of pulmonary artery,coronary artery and aorta between the two groups(P＞0.05).The mean subjective scores of pulmonary artery,coronary artery and aorta segments in the two groups were not less than 3 points,meeting the requirement of clinical diagnosis.There was no statistical difference in subjective scores between the two groups(P＞0.05).There was statistically significant difference in ED between the two groups(P＜0.05).The ED of pulmonary artery,coronary artery,and aorta in the experimental group were 11.49％,13.33％,and 11.46％significantly lower than those in the control group,respec-tively.Conclusion It is feasible to obtain TRO-CTA images used by the low radiation dose and low contrast dosage on the 320-row detector CT,and radiation dose and contrast dosage can be reduced reasonably without alterations of TRO-CTA images quality in clinical practice.

Oxidative stress is increasingly recognized as a major contributor to the pathophysiology of Alzheimer's disease(AD),particularly in the early stages of the disease.The multiplicity advantages of stem cell transplantation make it fascinating therapeutic strategy for many neurodegenerative diseases.We herein demonstrated that human dental pulp stem cells(hDPSCs)mediated oxidative stress improvement and neuroreparative effects in in vitro AD models,playing critical roles in regulating the polarization of hyperreactive microglia cells and the recovery of damaged neurons.Importantly,these therapeutic effects were reflected in 10-month-old 3xTg-AD mice after a single transplantation of hDPSCs,with the treated mice showing significant improvement in cognitive function and neuropathological features.Mechanistically,antioxidant and neuroprotective effects,as well as cognitive enhancements elicited by hDPSCs,were at least partially mediated by Nrf2 nuclear accumulation and downstream antioxidant enzymes expression through the activation of the AKT-GSK3β-Nrf2 signaling pathway.In conclusion,our findings corroborated the neuroprotective capacity of hDPSCs to reshape the neuropathological microenvironment in both in vitro and in vivo AD models,which may be a tremendous potential therapeutic candidate for Alzheimer's disease.

Oxidative stress is increasingly recognized as a major contributor to the pathophysiology of Alzheimer's disease(AD),particularly in the early stages of the disease.The multiplicity advantages of stem cell transplantation make it fascinating therapeutic strategy for many neurodegenerative diseases.We herein demonstrated that human dental pulp stem cells(hDPSCs)mediated oxidative stress improvement and neuroreparative effects in in vitro AD models,playing critical roles in regulating the polarization of hyperreactive microglia cells and the recovery of damaged neurons.Importantly,these therapeutic effects were reflected in 10-month-old 3xTg-AD mice after a single transplantation of hDPSCs,with the treated mice showing significant improvement in cognitive function and neuropathological features.Mechanistically,antioxidant and neuroprotective effects,as well as cognitive enhancements elicited by hDPSCs,were at least partially mediated by Nrf2 nuclear accumulation and downstream antioxidant enzymes expression through the activation of the AKT-GSK3β-Nrf2 signaling pathway.In conclusion,our findings corroborated the neuroprotective capacity of hDPSCs to reshape the neuropathological microenvironment in both in vitro and in vivo AD models,which may be a tremendous potential therapeutic candidate for Alzheimer's disease.

BACKGROUND: High-grade serous ovarian cancer (HGSOC) is the biggest cause of gynecological cancer-related mortality because of its extremely metastatic nature. This study aimed to explore and evaluate the characteristics of candidate factors associated with the metastasis and progression of HGSOC. METHODS: Transcriptomic data of HGSOC patients' samples collected from primary tumors and matched omental metastatic tumors were obtained from three independent studies in the National Center for Biotechnology Information (NCBI) Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) were selected to evaluate the effects on the prognosis and progression of ovarian cancer using data from The Cancer Genome Atlas (TCGA) database. Hub genes' immune landscapes were estimated by the Tumor Immune Estimation Resource (TIMER) database. Finally, using 25 HGSOC patients' cancer tissues and 10 normal fallopian tube tissues, immunohistochemistry (IHC) was performed to quantify the expression levels of hub genes associated with International Federation of Gynecology and Obstetrics (FIGO) stages. RESULTS: Fourteen DEGs, ADIPOQ , ALPK2 , BARX1 , CD37 , CNR2 , COL5A3 , FABP4 , FAP , GPR68 , ITGBL1 , MOXD1 , PODNL1 , SFRP2 , and TRAF3IP3 , were upregulated in metastatic tumors in every database while CADPS , GATA4 , STAR , and TSPAN8 were downregulated. ALPK2 , FAP , SFRP2 , GATA4 , STAR , and TSPAN8 were selected as hub genes significantly associated with survival and recurrence. All hub genes were correlated with tumor microenvironment infiltration, especially cancer-associated fibroblasts and natural killer (NK) cells. Furthermore, the expression of FAP and SFRP2 was positively correlated with the International Federation of Gynecology and Obstetrics (FIGO) stage, and their increased protein expression levels in metastatic samples compared with primary tumor samples and normal tissues were confirmed by IHC ( P = 0.0002 and P = 0.0001, respectively). CONCLUSIONS This study describes screening for DEGs in HGSOC primary tumors and matched metastasis tumors using integrated bioinformatics analyses. We identified six hub genes that were correlated with the progression of HGSOC, particularly FAP and SFRP2 , which might provide effective targets to predict prognosis and provide novel insights into individual therapeutic strategies for HGSOC.
Humans ; Female ; Ovarian Neoplasms/pathology* ; Prognosis ; Gene Expression Profiling ; Transcriptome ; Tumor Microenvironment ; Receptors, G-Protein-Coupled/therapeutic use* ; Tetraspanins/genetics* ; Protein Kinases ; Integrin beta1/therapeutic use*

Objective: To analyze the change trend of underground dust concentration, the incidence and survival status of pneumoconiosis patients, and provide reference for improving the working environment of dust-exposed workers and the prevention and treatment of pneumoconiosis patients in the future. Methods: In February 2020, a retrospective investigation was conducted on the dust data of underground mining operations in a steel enterprise in Jiangsu Province from 1991 to 2019, and the case data of patients diagnosed with pneumoconiosis from 1956 to 2019 were collected. The time trends of the number of pneumoconiosis patients and dust concentration, the stage of pneumoconiosis and survival status of patients were analyzed. Results: From 1956 to 2019, a total of 241 patients with pneumoconiosis were diagnosed in the steel enterprise. From 1991 to 2019, the annual average dust concentration in the mine showed a downward trend as a whole. Compared with the transportation platform (14.28%, 1447/10132) , the average dust concentration exceeding rate of the mining platform (43.68%, 8415/19263) was significantly higher (χ(2)=2674.84, P<0.01) . The average age of pneumoconiosis patients was (73.54±10.42) years old, and the average working age of dust exposure was (21.41±8.68) years, of which 85 cases (35.27%) survived and 156 cases (64.73%) died. The main type of pneumoconiosis was silicosis (90.46%, 218/241) , and the main stage of pneumoconiosis was the stage I (96.68%, 233/241) ; The higher the stage of pneumoconiosis, the younger the diagnosis age (P<0.01) . The average survival time of patients was (27.264±1.982) years, and the median survival time was 28 years. The cumulative survival rates of patients with pneumoconiosis in different diagnosis time periods were significantly different (χ(2)=35.57, P<0.01) . Conclusion: The improved dust-proof measures have a significant effect on reducing the concentration of underground dust. We need to focus on the dust control of underground mining platforms and the treatment of patients with stage Ⅲ pneumoconiosis.
Humans ; Middle Aged ; Aged ; Aged, 80 and over ; Child ; Adolescent ; Young Adult ; Adult ; Incidence ; Coal Mining ; Steel ; Retrospective Studies ; Pneumoconiosis/diagnosis* ; Dust ; Occupational Exposure/adverse effects*

Objective: To examine the association of body mass index (BMI) and waist circumference (WC) with frailty among oldest-old adults in China. Methods: A total of 7 987 people aged 80 years and older (oldest-old) who participated in the Chinese Longitudinal Healthy Longevity Survey (CLHLS) in 2017-2018 were included. Information on demographic characteristics, behavior pattern, diet, activities of daily living, cognitive function, health status, disease condition were collected by questionnaire and physical examination. Generalized linear mixed model and restricted cubic splines (RCS) were used to analyze the association of BMI and WC with frailty. Results: The mean age of all participants was 91.7 years, and their mean BMI and WC were (21.3±3.5) kg/m² and (82.9±10.5) cm, respectively. The proportion of male was 42.3% (3 377/7 987), and the proportion of people with frailty was 33.7% (2 664/7 987). After controlling confounding factors, compared with T₂ (19.1-22.1 kg/m²) of BMI, the OR (95%CI) of the female T₁ (<19.1 kg/m²) and T₃ (≥22.2 kg/m²) group was 1.39 (1.17-1.65) and 1.27 (1.07-1.52), respectively. Compared with T₂ (77-85 cm) of WC, the OR (95%CI) of female T₁ (<77 cm) and T₃ (≥86 cm) group was 1.20 (1.01-1.42) and 1.10 (0.93-1.31), respectively. The results of multiple linear regression model with restrictive cubic spline showed that there was a non-linear association of BMI and WC with frailty in female. Conclusion: There is a U-shaped association of BMI and WC with frailty in female participants.
Adult ; Male ; Female ; Humans ; Aged, 80 and over ; Waist Circumference ; Body Mass Index ; Frailty/epidemiology* ; Activities of Daily Living ; China/epidemiology* ; Risk Factors