BACKGROUND:Carnosic acid,a bioactive compound found in rosemary,has been shown to reduce inflammation and reactive oxygen species(ROS).However,its mechanism of action in osteoclast differentiation remains unclear. OBJECTIVE:To investigate the effects of carnosic acid on osteoclast activation,ROS production,and mitochondrial function. METHODS:Primary bone marrow-derived macrophages from mice were extracted and cultured in vitro.Different concentrations of carnosic acid(0,10,15,20,25 and 30 μmol/L)were tested for their effects on bone marrow-derived macrophage proliferation and toxicity using the cell counting kit-8 cell viability assay to determine a safe concentration.Bone marrow-derived macrophages were cultured in graded concentrations and induced by receptor activator of nuclear factor-κB ligand for osteoclast differentiation for 5-7 days.The effects of carnosic acid on osteoclast differentiation and function were then observed through tartrate-resistant acid phosphatase staining,F-actin staining,H2DCFDA probe and mitochondrial ROS,and Mito-Tracker fluorescence detection.Western blot and RT-PCR assays were subsequently conducted to examine the effects of carnosic acid on the upstream and downstream proteins of the receptor activator of nuclear factor-κB ligand-induced MAPK signaling pathway. RESULTS AND CONCLUSION:Tartrate-resistant acid phosphatase staining and F-actin staining showed that carnosic acid dose-dependently inhibited in vitro osteoclast differentiation and actin ring formation in the cell cytoskeleton,with the highest inhibitory effect observed in the high concentration group(30 μmol/L).Carnosic acid exhibited the most significant inhibitory effect during the early stages(days 1-3)of osteoclast differentiation compared to other intervention periods.Fluorescence imaging using the H2DCFDA probe,mitochondrial ROS,and Mito-Tracker demonstrated that carnosic acid inhibited cellular and mitochondrial ROS production while reducing mitochondrial membrane potential,thereby influencing mitochondrial function.The results of western blot and RT-PCR revealed that carnosic acid could suppress the expression of NFATc1,CTSK,MMP9,and C-fos proteins associated with osteoclast differentiation,and downregulate the expression of NFATc1,Atp6vod2,ACP5,CTSK,and C-fos genes related to osteoclast differentiation.Furthermore,carnosic acid enhanced the expression of antioxidant enzyme proteins and reduced the generation of ROS during the process of osteoclast differentiation.Overall,carnosic acid exerts its inhibitory effects on osteoclast differentiation by inhibiting the phosphorylation modification of the P38/ERK/JNK protein and activating the MAPK signaling pathway in bone marrow-derived macrophages.

Clinical trials have demonstrated that kilohertz-frequency transcutaneous spinal cord stimulation (TSCS) can be used to facilitate the recovery of sensory-motor function for patients with spinal cord injury, whereas the neural mechanism of TSCS is still undetermined so that the choice of stimulation parameters is largely dependent on the clinical experience. In this paper, a finite element model of transcutaneous spinal cord stimulation was used to calculate the electric field distribution of human spinal cord segments T ₁₂ to L ₂, whereas the activation thresholds of spinal fibers were determined by using a double-cable neuron model. Then the variation of activation thresholds was obtained by varying the carrier waveform, the interphase delay, the modulating frequency, and the modulating pulse width. Compared with the sinusoidal carrier, the usage of square carrier could significantly reduce the activation threshold of dorsal root (DR) fibers. Moreover, the variation of activation thresholds was no more than 1 V due to the varied modulating frequency and decreases with the increased modulating pulse width. For a square carrier at 10 kHz modulated by rectangular pulse with the frequency of 50 Hz and the pulse width of 1 ms, the lowest activation thresholds of DR fibers and dorsal column fibers were 27.6 V and 55.8 V, respectively. An interphase delay of 5 μs was able to reduce the activation thresholds of the DR fibers to 20.1 V. The simulation results can lay a theoretical foundation on the selection of TSCS parameters in clinical trials.
Humans ; Spinal Cord Stimulation/methods* ; Nerve Fibers/physiology* ; Finite Element Analysis ; Spinal Cord/physiology* ; Computer Simulation ; Spinal Cord Injuries/physiopathology* ; Lumbosacral Region ; Lumbar Vertebrae ; Transcutaneous Electric Nerve Stimulation/methods* ; Models, Neurological

Osteoporosis is a prevalent skeletal condition characterized by reduced bone mass and strength, leading to increased fragility. Buqi-Tongluo (BQTL) decoction, a traditional Chinese medicine (TCM) prescription, has yet to be fully evaluated for its potential in treating bone diseases such as osteoporosis. To investigate the mechanism by which BQTL decoction inhibits osteoclast differentiation in vitro and validate these findings through in vivo experiments. We employed MTS assays to assess the potential proliferative or toxic effects of BQTL on bone marrow macrophages (BMMs) at various concentrations. TRAcP experiments were conducted to examine BQTL's impact on osteoclast differentiation. RT-PCR and Western blot analyses were utilized to evaluate the relative expression levels of osteoclast-specific genes and proteins under BQTL stimulation. Finally, in vivo experiments were performed using an osteoporosis model to further validate the in vitro findings. This study revealed that BQTL suppressed receptor activator of NF-κB ligand (RANKL)-induced osteoclastogenesis and osteoclast resorption activity in vitro in a dose-dependent manner without observable cytotoxicity. The inhibitory effects of BQTL on osteoclast formation and function were attributed to the downregulation of NFATc1 and c-fos activity, primarily through attenuation of the MAPK, NF-κB, and Calcineurin signaling pathways. BQTL's inhibitory capacity was further examined in vivo using an ovariectomized (OVX) rat model, demonstrating a strong protective effect against bone loss. BQTL may serve as an effective therapeutic TCM for the treatment of postmenopausal osteoporosis and the alleviation of bone loss induced by estrogen deficiency and related conditions.
Animals ; NFATC Transcription Factors/genetics* ; Drugs, Chinese Herbal/pharmacology* ; Ovariectomy ; Osteoclasts/metabolism* ; Female ; Osteogenesis/drug effects* ; Rats, Sprague-Dawley ; Rats ; NF-kappa B/genetics* ; Osteoporosis/genetics* ; Signal Transduction/drug effects* ; Bone Resorption/genetics* ; Cell Differentiation/drug effects* ; Humans ; RANK Ligand/metabolism* ; Mitogen-Activated Protein Kinases/genetics* ; Transcription Factors

Objective To investigate the safety and clinical effect of prophylactic ileostomy using right lower abdominal specimen extraction incision in laparoscopic rectal low anterior resection and its impact on ileos-tomy closure.Methods A retrospective analysis was conducted on 127 patients who underwent laparoscopic low anterior resection of rectal cancer combined with prophylactic ileostomy in Department of General Surgery in our hospital from January 2020 to December 2023.Patients were divided into observation group(n=60)and control group(n=67)based on whether with prophylactic ileostomy using the right lower abdominal specimen extraction incision or not.Relevant data and clinical data of ileostomy closure were compared between the two groups.Results(1)There was no significant difference in baseline clinical data between the two groups(P>0.05).(2)In terms of operation time,pain score within three days after surgery and postoperative first exhaust time,the observation group was better than the control group,showing statistical difference(P<0.05).In the observation group,the average length of the incision was longer than that in the control group,and it was significantly different between the two groups(P<0.05).There was no significant difference between the two groups in terms of blood loss,post-operative feeding time and postoperative hospital stay(P>0.05).(3)There was no significant difference between the two groups in postoperative and ostomy-related complication S(P>0.05).(4)The observation group was better than the control group in terms of postoperative pain score and postoperative first exhaust time,indicating statistical significance(P<0.05).There were no significant differences in surgical time,abdominal adhesion,blood loss,postoperative hospital stay and postoperative complications between the two groups(P>0.05).Conclusion The patients undergoing laparoscopic rectal low anterior resection who needs prophylactic ileostomy using right lower abdominal specimen extraction incision can improve the appearance of the incision,shorten operation time,reduce postoperative pain of the patients but does not increase postoperative complications and the difficulty of ileostomy closure.It is safe and feasible,which worthy for clinical promotion.

Background::Hypothermia therapy has been suggested to attenuate myocardial necrosis; however, the clinical implementation as a valid therapeutic strategy has failed, and new approaches are needed to translate into clinical applications. This study aimed to assess the feasibility, safety, and efficacy of a novel selective intracoronary hypothermia (SICH) device in mitigating myocardial reperfusion injury.Methods::This study comprised two phases. The first phase of the SICH was performed in a normal porcine model for 30 minutes ( n = 5) to evaluate its feasibility. The second phase was conducted in a porcine myocardial infarction (MI) model of myocardial ischemia/reperfusion which was performed by balloon occlusion of the left anterior descending coronary artery for 60 minutes and maintained for 42 days. Pigs in the hypothermia group ( n = 8) received hypothermia intervention onset reperfusion for 30 minutes and controls ( n = 8) received no intervention. All animals were followed for 42 days. Cardiac magnetic resonance analysis (five and 42 days post-MI) and a series of biomarkers/histological studies were performed. Results::The average time to lower temperatures to a steady state was 4.8 ± 0.8 s. SICH had no impact on blood pressure or heart rate and was safely performed without complications by using a 3.9 F catheter. Interleukin-6 (IL-6), tumor necrosis factor-α, C-reactive protein (CRP), and brain natriuretic peptide (BNP) were lower at 60 min post perfusion in pigs that underwent SICH as compared with the control group. On day 5 post MI/R, edema, intramyocardial hemorrhage, and microvascular obstruction were reduced in the hypothermia group. On day 42 post MI/R, the infarct size, IL-6, CRP, BNP, and matrix metalloproteinase-9 were reduced, and the ejection fraction was improved in pigs that underwent SICH.Conclusions::The SICH device safely and effectively reduced the infarct size and improved heart function in a pig model of MI/R. These beneficial effects indicate the clinical potential of SICH for treatment of myocardial reperfusion injury.

ObjectiveTo investigate the current status of personnel training, barriers and bottlenecks at Shanghai Municipal and district Centers for Disease Control and Prevention (hereinafter referred to as" CDC"), so as to provide a reference basis for the formulation of training policies that are consistent with the CDC’s staff development path, characteristics of the era, and features of Shanghai mega⁃city. MethodsQuestionnaire survey and qualitative interview were used to collect the data, covering the basic information of the research subjects, as well as training status, needs, barriers and problems. A total of 800 questionnaires were distributed, and 768 valid questionnaires were returned, and frequency counts and composition ratios were used for statistical description. ResultsAmong the research subjects, 568 of which were females, accounting for 73.96%, with an average age of 36.51 years. Almost 93.10% of the research subjects had participated in training in the last year, while 6.90% of whom hadn’t attended any kind of training ever, with the main reasons as follows: failure to receive notification of training, unavailability of work, lack of funding, limited number of places and unsuitable content. Furthermore, 12.63% of the research subjects thought the trainings provided could not satisfy the requirements for continuing medical education credits, and the top three common forms of training were lectures/conferences, training courses with credits, and online courses. 97.27% of the research subjects had a need for training, and 56.12% of which expected to train for 2‒3 days, and the ideal number of training sessions per year was 2‒3 and 4‒5 times. All the staff, whether they were from the municipal CDC or district CDC, preferred practical training and case lectures to theoretical lectures. However, staff from municipal CDC had a higher demand for official document writing and research project design, and staff from district CDC had a higher demand for data software analysis and thesis writing. Bottlenecks mainly included some training needs incapable of being satisfied currently, single form of training that didn’t take advantage of the support of digital technology and lacked flexibility and convenience, and a lack of channels and mechanisms for the dissemination and transmission of training information. ConclusionStrategies to improve the training of CDC personnel at both the district and municipal levels include the creation of a hierarchical and progressive training model and system for different populations, an extension of training forms, containing the establishment of a unified training platform and the creation of an online knowledge base; and the construction of a unified and open platform with a smooth release and transfer mechanism for the dissemination of training information.

Objective:To compare the accuracy and efficacy of robot assisted and navigation assisted pedicle screw fixation.Methods:Retrospective analysis of 764 patients with lumbar spine disorders who underwent internal fixation treatment at the Department of Spine Surgery, Honghui Hospital, Xi'an Jiaotong University, from June 2017 to April 2023 were performed. They were divided into the Renaissance group (212 cases), the Tinavi group (301 cases), and the S8 navigation group (251 cases), according to the method of assisted placement of pedicle screws. The operation time, fluoroscopy time, X-ray radiation dose, intra-operative blood loss, accuracy of screw placement, screw revision rate, pain visual analogue scale (VAS), Oswestry disability index (ODI) and postoperative infection rate were compared among the three groups.Results:922 screws were placed in the Renaissance group, 1,260 screws in the Tinavi group, and 1,044 screws in the S8 navigation group. The accuracy of clinically acceptable pedicle screw placement was 92.08% (849/922), 99.68% (1,256/1,260), and 99.43% (1,038/1,044) in the three groups, respectively, with the Renaissance group being smaller than the Tinavi group and the S8 group (χ 2=90.334, P<0.001; χ 2=68.446, P<0.001), and the Tinavi group and the S8 group had no statistically significant difference (χ 2=0.380, P=0.537). The operation time of the three groups was 173.64±62.23 min, 177.11±60.85 min, 176.02±60.93 min, and the intraoperative blood loss was 118.16±58.26 ml, 121.84±55.91 ml, 123.62±59.84 ml, respectively, and the differences between the groups were not statistically significant ( P>0.05). The fluoroscopy time of the three groups was 8.73±2.92 s, 10.67±2.85 s, and 11.31±2.89 s, and the X-ray radiation doses were 18.83±7.41 μSv, 20.40±7.60 μSv, and 22.88±7.47 μSv, respectively, with statistically significant differences between the groups and the two comparisons ( P<0.05). All patients were given follow-up for 3-30 months. Three cases in the postoperative Renaissance group underwent screw revision for nerve root irritation due to screw penetration of the pedicle cortex, and none of the other two groups underwent screw revision. Postoperatively, one case in the Renaissance group and one case in the Tinavi group had superficial infections, which were cured after prolonged antibiotic use. At 3 months postoperatively, the VAS scores for leg pain in the Renaissance group, the Tinavi group, and the S8 navigation group were 3.52±1.14, 3.59±1.12, and 3.39±1.16, and the VAS scores for back pain were 3.54±1.14, 3.57±1.12, and 3.51±1.15, respectively; the ODI scores were 12.48%±4.53%, 12.01%±4.57%, and 12.28%±4.60%, and none of the differences between the groups were statistically significant ( P>0.05). Conclusion:The accuracy of screw placement by the Tinavi robot was comparable to that of the S8 navigation, and both were superior to that of the Renaissance robot; the fluoroscopy time and radiation dose of the Renaissance robot were smaller than those of the Tinavi robot, which was smaller than that of the S8 navigation. The early efficacy of robotics and navigation-assisted pedicle screw internal fixation for lumbar spine disorders is similar.

Purpose To explore the value of a prediction model based on diffusion weighted imaging(DWI)deep learning features in endometrial cancer microsatellite instability status assessment.Materials and Methods DWI data of 32 microsatellite instability and 55 microsatellite stability endometrial cancer patients were analysed from June 2020 to April 2023 in Xinxiang Central Hospital,retrospectively.Apparent diffusion coefficient(ADC)values of the primary lesions were measured,and deep learning features and imaging histological features of the primary lesions were extracted using multilayer convolutional neural networks and PyRadiomics,respectively.The least absolute shrinkage and selection operator and random forest were used for feature screening and model building,respectively.The area under the receiver operating characteristic curve(AUC)and net reclassification improvement were used to evaluate model performance.Bootstrap based on 1 000 resamples was used for internal validation of the model.Results For the deep learning model,a total of 6 features were included,the 7th,57th,77th,82nd,97th and 108th features,with an AUC of 0.905(95％CI 0.823-0.957);for the radiomics model,a total of 6 features were included,1 neighborhood grey level difference matrix,4 grey level region size matrices and 1 grey level tour length matrix feature,with an AUC was 0.844(95％CI 0.751-0.913);for ADC values,the microsatellite instability group had smaller ADC values than the microsatellite stability group(t=-4.123,P＜0.001),with an AUC of 0.810(95％CI 0.712-0.886).Compared with the radiomics model and ADC values,the deep learning model showed improved risk prediction,with net reclassification improvements of 0.856 and 0.486(P＜0.01,P=0.024),respectively.In Bootstrap-based internal validation,the deep learning model also demonstrated higher performance than the radiomics model,with AUCs of 0.897(95％CI0.889-0.905)and 0.829(95％CI0.812-0.839),respectively.Conclusion A prediction model based on deep learning features of DWI images can provide a better assessment of microsatellite instability status in endometrial cancer patients than radiomics model and ADC values.

Objective:To explore the influence of central obesity on the risk of breast cancer and the possible role of dietary factors in its prevention.Methods:This study is a case-control study including a total of 212 participants, of whom 63 were with breast cancer, 71 were with breast nodules, and 80 were healthy controls. We used bioelectrical impedance analysis to measure body composition,and adopted the food frequency questionnaire to investigate dietary intake of participants.Results:The visceral adipose tissue ( OR=1.03, 95% CI: 1.003 to 1.077) and trunk fat mass ( OR=1.470, 95% CI: 1.104 to 2.184) were independently associated with the increased risk of breast cancer. Dietary patterns characterized by low dietary intake of beans and dairy products ( OR=1.300, 95% CI: 1.044 to 1.619) and high intake of cereals and red meat ( OR=2.254, 95% CI: 1.705 to 2.982) will increase the risk of breast cancer. Moreover, high meat intake ( β=0.268, 95% CI: 0.034 to 0.503) would advance the accumulation of visceral fat, while high bean intake ( β=-0.485, 95% CI: -0.865 to -0.104) would inhibit. Conclusions:Central obesity is an independent risk factor for breast cancer. Insufficient intake of beans and excessive intake of red meat are identified as factors that can exacerbate central obesity in breast cancer patients.

Objective:To study the efficacy of Alteplase in repairing T-lymphocyte mediated brain tissue immunoinflammatory damage after acute ischemic stroke(AIS).Methods:A total of 100 patients with AIS admitted to Hengshui People's Hospital from June 2022 to June 2023 were selected,and divided into regular group and Alteplase group,with 50 cases in each group,after enroll-ment,the regular group received routine intervention treatment,while the Ateplase group received thrombolytic therapy with Ateplase.Compared changes in neurological function,cerebrovascular reserve function,cerebral hemodynamics,T lymphocytes mediated brain tissue immunoinflammatory damage indicators CD4+T cell subsets[pro-inflammatory cells(Th1,Th17),anti-inflammatory cells(Th2,Treg cells)]and related cytokines levels between two groups of patients,and evaluated clinical efficacy and prognosis.Results:After treatment,NIHSS score of Alteplase group was lower than that of regular group[(6.57±0.79)points vs(9.34±1.23)points,t=13.400,P<0.05].CVR and BHI of cerebral vascular reserve in Alteplase group were higher than those in regular group[(34.54±4.35)%vs(29.89±2.31)%,1.00±0.23 vs 0.92±0.08,t=6.676,2.323,P<0.05],PI was lower than that of regular group(0.60±0.07 vs 0.72±0.08,t=7.982,P<0.05).Cerebral hemodynamic CBF of Alteplase group was higher than that of regular group[(49.89±9.76)ml/(100 g/min)vs(40.34±7.86)ml/(100 g/min),t=5.389,P<0.05].MTT and TTP were shorter than those in regular group[(6.45±0.78)s vs(9.78±1.02)s,(24.45±2.16)s vs(26.78±3.25)s,t=18.340,4.222,P<0.05].Proportion of Th1 and Th17 cells and levels of IFN-γ and IL-17 in Ateplase group were lower than those in regular group[(3.27±0.59)%vs(5.64±0.52)%,(2.34±0.25)%vs(4.35±0.38)%,(3.24±0.45)pg/ml vs(4.90±0.65)pg/ml,(10.23±1.43)pg/ml vs(14.35±2.14)pg/ml,t=21.310,31.250,14.850,11.320,P<0.05),proportion of Th2 and Treg cells and levels of IL-4 and TGF-β were higher than those in regular group[(8.75±0.54)%vs(7.02±0.37)%,(7.24±2.13)%vs(5.88±1.67)%,(13.24±2.16)pg/ml vs(10.26±1.29)pg/ml,(90.32±9.02)pg/ml vs(81.45±8.97)pg/ml,t=18.690,3.553,8.375,4.930,P<0.05].Total effective rate and good prognosis rate of Alteplase group were higher than those of regular group(94.00%vs 80.00%,80.00%vs 62.00%,χ2=4.332,3.934,P<0.05).Conclu-sion:In treatment of AIS,Alteplase has effect of repairing the immune inflammation injury of brain tissue mediated by T lymphocytes,alleviating brain injury,improving cerebrovascular reserve function and nerve function,and the prognosis is good.