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 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.

Child ; Humans ; Circulating Tumor DNA ; Lymphangioma ; Family ; Hemangioendothelioma ; Sarcoma, Kaposi

ObjectiveTo investigate the effect of Shunao Jieyu decoction on intestinal flora in patients with post-stroke depression. MethodSixty patients with post-stroke depression of Qi stagnation， blood stasis， and phlegm obstruction were selected and divided into a treatment group （30 cases， Shunao Jieyu decoction） and a control group （n=30， paroxetine hydrochloride tablets） according to the random number table. All patients were treated correspondingly for eight weeks. The scores of traditional Chinese medicine（TCM） syndrome， Hamilton rating scale for depression（HAMD）， National Institutes of Health stroke scale（NIHSS）， and activities of daily living（ADL）before and after treatment were compared between the two groups. High-throughput sequencing was used to analyze the diversity of fecal flora and the distribution of taxonomical levels in two groups before and after treatment. ResultThe post-treatment TCM syndrome score， HAMD score， and NIHSS score were lower than those before treatment in the same group （P<0.05）， while the post-treatment ADL score was higher than that before treatment （P<0.05）. Compared with the control group after treatment， the treatment group showed decreased TCM syndrome score （P<0.05）. No significant difference was observed in the HAMD score， NIHSS score and ADL score between the two groups after treatment. The total effective rate of the treatment group was 90% （27/30）， which was superior to 66.3% （19/30） of the control group （χ²=5.863， P<0.05）. After treatment， the average values of Chao1 index， Observed species index， Shannon index， Simpson index， and Pielou's evenness index of intestinal flora diversity in the treatment group increased without significant difference， while the average value of the Good's Coverage index remained unchanged in the same group. At the phylum level， the abundance of Bacteroidetes increased. At the family level， the abundance of Bacteroidaceae increased. At the genus level， the abundance of Bacteroidetes increased. ConclusionShunao Jieyu decoction can effectively improve the clinical TCM symptoms of patients with post-stroke depression， relieve neurological impairment， improve the ability of daily living， and change the diversity and abundance of the intestinal flora of patients at different taxonomic levels.

The mechanisms underlying exercise-induced neuroprotective effects after traumatic brain injury (TBI) remained elusive, and there is a lack of effective treatments for TBI. In this study, we investigated the effects of an integrative approach of exercise and Yisaipu (TNFR-IgG fusion protein, TNF inhibitor) in a mouse TBI model. Male C57BL/6J mice were randomly assigned to a sedentary group or a group that followed a voluntary exercise regimen. The effects of 6-week prophylactic preconditioning exercise (PE) alone or in combination with post-TBI Yisaipu treatment on moderate TBI associated deficits were examined. The results showed that combined treatments of PE and post-TBI Yisaipu were superior to single treatments on reducing sensorimotor and gait dysfunctions in mice. These functional improvements were accompanied by reduced systemic inflammation largely via decreased serum TNF-α, boosted autophagic flux, and mitigated lesion volume after TBI. Given these neuroprotective effects, composite approaches such as a combination of exercise and TNF inhibitor may be a promising strategy for facilitating functional recovery from TBI and are worth further investigation.
Animals ; Brain Injuries, Traumatic/pathology* ; Disease Models, Animal ; Male ; Mice ; Mice, Inbred C57BL ; Neuroprotective Agents/pharmacology* ; Recovery of Function ; Tumor Necrosis Factor Inhibitors

This study aimed to investigate the effect of methyl eugenol(ME) on hypoxia/reoxygenation(H/R)-induced injury of human renal tubular epithelial HK-2 cells and its mechanism. The viability of HK-2 cells cultured with different concentrations of ME and exposed to H/R was detected by cell counting kit-8(CCK-8) assay. The effect of ME on the morphology of HK-2 cells was observed under an inverted microscope. The content of intracellular reactive oxygen species in different groups was detected after 2',7'-dichlorodihydrofluorescein diacetate(DCFH-DA) fluorescence staining. Cell apoptosis was determined by flow cytometry. Changes in mitochondrial membrane potential were monitored by JC-1 dye. The concentrations of nuclear factor erythroid 2 related factor 2(Nrf2), heme oxygenase-1(HO-1), and nicotinamide adenine dinucleotide phosphatase oxidase 4(Nox4) were measured by Western blot, followed by the assay of Nrf2 concentration changes in cytoplasm and nucleus by confocal fluorescence staining. The results showed that when the concentration of ME was 0-40 μmol·L~(-1), the activity of HK-2 cells was not affected. Compared with the model group, ME enhanced the activity of HK-2 cells and the cell morphology was normal. As revealed by further experiments, ME inhibited the release of reactive oxygen species and the decline in mitochondrial membrane potential of HK-2 cells after H/R injury, promoted Nrf2/HO-1 expression and Nrf2 translocation to the nucleus, and down-regulated the expression of Nox4, thereby significantly reducing apoptosis. This protective effect of ME could be reversed by the specific Nrf2 inhibitor ML385. These findings have preliminarily proved that ME effectively protected HK-2 cells against H/R injury, which might be related to its promotion of Nrf2/HO-1 signaling pathway and inhibition of Nox4. Such exploration on the possible mechanism of ME in the treatment of renal ischemia-reperfusion injury(IRI) and protection of organ function from the perspective of antioxidant stress has provided reference for related research on the treatment of acute kidney injury with traditional Chinese medicine.
Apoptosis ; Epithelial Cells/metabolism* ; Eugenol/pharmacology* ; Heme Oxygenase-1/metabolism* ; Humans ; Hypoxia ; NF-E2-Related Factor 2/metabolism* ; Oxidative Stress ; Reactive Oxygen Species ; Reperfusion Injury/drug therapy*

【Objective】 To compare the diagnostic efficacy of full-field digital mammography(FFDM), digital breast mammography(DBT) and dynamic enhanced magnetic resonance imaging(DCE-MRI) for breast tumors in different gland types. 【Methods】 Retrospective analyses of 56 breast lesions in 49 patients who underwent FFDM, DBT and MRI in the Department of Radiology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University from October 2018 to December 2019 were performed. The breasts were divided into the non-dense or dense pattern, according to FFDM images. The breast lesions were diagnosed as benign(BI-RADS grade 4a and below) or malignant(BI-RADS grade 4b and above), based on the images of FFDM, DBT and MRI, respectively. All patients underwent surgery or biopsy to get a pathological diagnosis. The kappa consistency tests and receiver operating characteristics(ROC) analyses were used to compare the efficacy of FFDM, DBT and MRI in the diagnosis of breast tumor in different gland patterns. 【Results】 In all breasts, MRI (kappa = 0.66) was moderately consistent with pathological diagnosis, which was higher than DBT(kappa = 0.44), while there was no significant difference between FFDM(kappa = 0.14) and pathological diagnosis. In non-dense breasts, MRI (kappa = 0.88) was moderately consistent with pathological diagnosis, which was higher than DBT(kappa = 0.51), while there was no significant difference between FFDM(kappa = 0.18) and pathological diagnosis. In dense breasts, MRI(kappa = 0.54) was moderately consistent with pathological diagnosis, which was higher than DBT(kappa = 0.37), while there was no significant difference between FFDM(kappa = 0.10) and pathological diagnosis. In all breasts, the diagnostic efficacy of MRI, DBT and FFDM for breast tumor decreased gradually(AUC = 0.83; 0.73; 0.58). Specifically, the specificity of MRI, DBT and FFDM increased sequentially(77%, 82%, 86%), but the sensitivity decreased(88%, 65%, 29%). In non-dense breasts, the diagnostic efficacy of MRI, DBT and FFDM for breast tumor decreased gradually(AUC = 0.97; 0.84; 0.66). Specifically, the sensitivity of MRI(94%) was higher than that of DBT(69%) and FFDM(31%). In dense breasts, the diagnostic efficacy of MRI, DBT and FFDM for breast tumor decreased gradually(AUC = 0.77; 0.69; 0.55). Specifically, the specificity of MRI, DBT and FFDM increased sequentially(71%, 76%, 82%), but the sensitivity decreased(83%, 61%, 28%) . 【Conclusions】 In both dense and non-dense breasts, FFDM has the lowest diagnostic ability. In non-dense breasts, the diagnostic efficacy of MRI is higher than DBT. DBT shows its advantage over MRI in dense breasts, as it has a higher diagnostic specificity.

Alkali-salinity exerts severe osmotic, ionic, and high-pH stresses to plants. To under-stand the alkali-salinity responsive mechanisms underlying photosynthetic modulation and reactive oxygen species (ROS) homeostasis, physiological and diverse quantitative proteomics analyses of alkaligrass (Puccinellia tenuiflora) under Na2CO3 stress were conducted. In addition, Western blot,real-time PCR, and transgenic techniques were applied to validate the proteomic results and test the functions of the Na2CO3-responsive proteins. A total of 104 and 102 Na2CO3-responsive proteins were identified in leaves and chloroplasts, respectively. In addition, 84 Na2CO3-responsive phospho-proteins were identified, including 56 new phosphorylation sites in 56 phosphoproteins from chloro-plasts, which are crucial for the regulation of photosynthesis, ion transport, signal transduction, and energy homeostasis. A full-length PtFBA encoding an alkaligrass chloroplastic fructose-bisphosphate aldolase (FBA) was overexpressed in wild-type cells of cyanobacterium Synechocystis sp. Strain PCC 6803, leading to enhanced Na2CO3 tolerance. All these results indicate that thermal dissipation, state transition, cyclic electron transport, photorespiration, repair of pho-tosystem (PS) Ⅱ, PSI activity, and ROS homeostasis were altered in response to Na2CO3 stress, which help to improve our understanding of the Na2CO3-responsive mechanisms in halophytes.

OBJECTIVETo explore the apoptosis mechanism of Wenxia Changfu Formula (, WCF) in reversing drug resistance of lung cancer in vivo.

METHODSThirty model mice were randomly assigned to three groups: control group, cisplatin (CDDP) group, and WCF group. A transplanted tumor model of lung adenocarcinoma was established in all groups. Mice in the WCF group received intragastric administration of WCF (0.2 mL/10 g body weight) everyday in addition to CDDP intraperitoneally (5 mg/kg body weight) twice a week. The mice in the CDDP group received CDDP intraperitoneally (5 mg/kg body weight) twice a week, while the control group received normal saline intraperitoneally (0.2 mL/10 g body weight) everyday. The weight of the nude mice and respective tumors, tumor volume and tumor-inhibiting rate were measured. Electron microscopy was used to observe the existence of apoptosis body. Apoptosis index (AI) was detected by TdT-mediated dUTP nick end labeling staining. The expression of Fas and FasL mRNA was investigated by reverse transcription polymerase chain reaction, while immunohistochemistry was applied to detect the protein expression of Fas and FasL, caspase-3 and caspase-activated DNase (CAD), respectively.

RESULTSCompared with CDDP group and control group, WCF could significantly reduce the tumor volume from the 19th day and alleviate the tumor weight (P <0.05), and the apoptosis body was found in tumor cells in the WCF group. WCF could also enhance the level of AI, up-regulate the expression of caspase apoptosis pathway related protein caspase-3 and CAD, as well as the expression of Fas, FasL mRNA and protein (P <0.05).

CONCLUSIONWCF could improve the sensitivity of tumor cells to CDDP and reverse the drug resistance by inducing the apoptosis.

Adenocarcinoma ; drug therapy ; pathology ; Animals ; Apoptosis ; drug effects ; Caspase 3 ; metabolism ; Cell Line, Tumor ; Chromatography, High Pressure Liquid ; Cisplatin ; pharmacology ; Drug Resistance, Neoplasm ; drug effects ; Drugs, Chinese Herbal ; pharmacology ; therapeutic use ; Fas Ligand Protein ; genetics ; metabolism ; Female ; Fluorescent Antibody Technique ; Humans ; In Situ Nick-End Labeling ; Lung Neoplasms ; drug therapy ; pathology ; Mice, Nude ; RNA, Messenger ; genetics ; metabolism ; Tumor Burden ; drug effects ; Xenograft Model Antitumor Assays ; fas Receptor ; metabolism

OBJECTIVE: To observe the impact of energy saving light,incandescent light and circadian light on the ethology of depressive rats and explore its possible mechanism on affecting the secretion of melatonin. METHODS: Thirty rats aged 6weeks were randomly selected from 40 specific pathogen free health female SD rats after they adapted to the living environment,depressive rat models were established in the rats by bilateral ovariectomy combined with isolated living and chronic unpredictable mild stress stimulation at the age of 11-14 weeks. Then these 30 ovariectomized rats were randomly divided into 3 intervention groups,including an energy saving light group,an incandescent light group and a circadian light group,with 10 rats in each group. The rats in these 3 groups were given specific experimental light intervention for 3 weeks respectively at the age of 17 weeks. The other 10 rats were raised in conventional environment as the control group. Their body weights were measured at the age of 17,19,20 and 21 weeks. The ethology tests were carried out by sucrose preference test and the open-field test at the age of 7,14 and 20 weeks respectively. The melatonin levels in peripheral blood of 7 time points from 19: 30 to 8: 30 were measured in the rats at age of 21 weeks. One rat in each group at every time point was randomly selected for examination. RESULTS: At the age of 17 weeks before light-intervention,the body weights of rats in 4 groups showed no significant difference( P > 0. 05). After light-intervention,at the age of 17-20 weeks,the body weights of rats in 3 intervention groups were gradually increased with the increase of age( P < 0. 05).There was no significant difference between body weights of rats at the age of 21 weeks and those at the age of 20 weeks in each group( P > 0. 05). At age of 7 weeks,no significant differences were found in sucrose consumption and standing scores among these 4 groups( P > 0. 05). After the depressive models were established,at the age of 14 weeks before light-intervention,in rats of these 3 intervention groups,the sucrose consumption and standing scores were lower than those of the control group( P < 0. 05),and there was no significant difference found in the above 2 indexes among these 3intervention groups( P > 0. 05). At the age of 20 weeks after light-intervention,the sucrose consumption and standing scores were not significantly different from each other among the 4 groups( P > 0. 05). The peak levels of melatonin in the peripheral blood of rats in these 3 intervention groups were higher than that in the control group. The peak levels onsets of melatonin in peripheral blood of rats in the circadian light group and the energy saving light group were earlier or 2 hours delayed compared to that of control group,while it was similar between the incandescent light group and control group.CONCLUSION: The circadian light,the energy saving light and the incandescent light are similarly effective in improving the behaviors of depressive rats. The circadian light can delay the onset of peak level of melatonin in peripheral blood.