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.

OBJECTIVE To systematically evaluate the methodological quality of the postoperative chemotherapy guidelines/ consensuses for ovarian epithelial tumor. METHODS A search was conducted across databases including PubMed， Embase， Web of Science， CBM， VIP， Chinese Medical Journal Data， Wanfang Data， and CNKI， as well as the official websites of GIN， NICE， Medlive， AHRQ， CSCO， ASCO， and NCCN. The search period was from the establishment of the databases/websites to March 10， 2025. The quality of the included guidelines/consensus was evaluated by using the AGREE-Ⅱ tool. RESULTS A total of 16 guidelines/consensuses were included. The domain scores of AGREE-Ⅱ evaluation were as follows： scope and purpose of 85.07%， participants of 47.92%， rigor of development of 57.49%， clarity of presentation of 88.02%， applicability of 8.20%， and independence of 53.39%. Among them， 14 were recommended at grade B and 2 were recommended at grade C. The subgroup analysis by different countries/regions and different types of studies showed that the scores for participants， rigor of development， and independence of the guidelines/consensuses in China were significantly lower than foreign countries （P＜0.05）； the scores for participants and rigor of development of the guidelines were significantly higher than consensuses （P＜0.05）. The guideline/ consensus recommendation results indicated that grade B guidelines/consensus recommend platinum-based combination chemotherapy as the preferred adjuvant chemotherapy regimen for stage Ⅰ high-grade serous carcinoma patients；platinum-based combination chemotherapy±bevacizumab was recommended as the preferred adjuvant chemotherapy regimen for stage Ⅱ-Ⅳ high- grade serous carcinoma patients and for platinum-sensitive recurrent high-grade serous carcinoma patients； non-platinum single- agent chemotherapy±bevacizumab was recommended as the preferred chemotherapy regimen for platinum-resistant recurrent high- grade serous carcinoma patients. CONCLUSIONS The overall quality of postoperative chemotherapy guidelines/consensuses for ovarian epithelial tumor is not high. The methodological quality of guidelines/consensuses in China is still lagging behind that of foreign countries. The recommendations differ from those in foreign countries. It is recommended to improve the aspects of participants， rigor of development， and independence， to recommend treatment plans based on the different stages of ovarian cancer， and develop guidelines/consensuses that align with China’s national conditions.

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

Objective To investigate the impact of anti-reflux modified duodenal exclusion surgery on glucose metabolism in rats with type 2 diabetes mellitus (T2DM), and to elucidate the role of the duodenum in maintaining glucose homeostasis. MethodsForty male Sprague-Dawley rats aged 5 weeks were fed a high-fat diet and induced with T2DM using low-dose streptozotocin. Thirty-six rats that met the T2DM model criteria were randomly divided into three groups: the simple duodenal exclusion surgery group (DE group), the anti-reflux modified duodenal exclusion group (MDE group), and the sham operation group (SO group), with 12 rats in each group. Gastroenterography was performed 4 weeks after surgery, and the body weight, fasting blood glucose levels, and serum glucagon-like peptide-1 (GLP-1) concentrations were measured before surgery and at 1, 2, 4, and 8 weeks post-surgery. Eight weeks post-surgery, the rats were euthanized, and a 1 cm segment of the biliopancreatic loop was collected from each group for pathological sectioning and HE staining to observe the intestinal mucosal villus length under an optical microscope. Results Gastroenterography showed that there was significant reflux of the contrast agent into the duodenal lumen in the DE group, while no reflux was observed in the MDE group. At one week post-surgery, the body weights of rats in all three groups significantly decreased compared to before surgery (P<0.05), and then the body weights of all groups increased over time, with no significant differences between the groups (P>0.05). Compared with the SO group, the fasting blood glucose levels in the MDE and DE groups significantly decreased at all time points post-surgery (P<0.05), while GLP-1 concentrations significantly increased (P<0.05). The fasting blood glucose levels in the MDE group were lower than those in the DE group at all time points post-surgery (P<0.05), but there were no significant differences in serum GLP-1 concentrations between the MDE and DE groups (P>0.05). Regarding intestinal mucosal morphology, the villus lengths of the biliopancreatic loops in the MDE group were significantly shorter than those in the DE and SO groups (P<0.05). Conclusion Anti-reflux modified duodenal exclusion surgery effectively improves glucose metabolism in T2DM rats by preventing the reflux of chyme into the diverted duodenum, thereby enhancing its hypoglycemic effect.

Objective:To evaluate the effect of accelerated rehabilitation surgery (ERAS) under diagnosis-intervention packet (DIP) in patients with early cancer of digestive tract undergoing endoscopic submucosal dissection (ESD).Methods:The 64 patients with early cancer of digestive tract treated with ESD in the Gastroenterology Department of the Second People′s Hospital of Jiaozuo were selected by randomized controlled trial and convenient sampling method. According to random number table method, they were divided into routine group and observation group, 32 patients in each group. All patients in the 2 groups paid their medical expenses by DIP method, the routine group was treated with traditional perioperative nursing, and the observation group was treated with ERAS perioperative management mode. The postoperative complication rate, length of hospital stay, DIP allocation ratio, and patient satisfaction with nursing were compared between the two groups.Results:There were 16 men and women in the routine group, 14 men and 18 women in the observation group.After intervention, the incidence of postoperative complications was 21.88% (7/32) in the routine group and 3.12% (1/32) in the observation group, and the difference between the two groups was statistically significant ( χ2=5.14, P<0.05). The length of stay was (10.93 ± 2.87) d in the routine group and (9.01 ± 1.53) d in the observation group, and the difference between the two groups was statistically significant ( t=4.13, P<0.05). The average hospitalization expenses per case was (20 108.23 ± 6 495.49) yuan in the routine group and (18 589.03 ± 4 439.46) yuan in the observation group, and the difference between the two groups was statistically significant ( t=20.57, P<0.05). The DIP allocation ratio of the observation group was 87.98% (303 419.26/344 872.99), and that of the routine group was 69.33% (244 864.99/353 187.65), and the difference between the two groups was statistically significant ( χ2=4.81, P<0.05). The satisfaction of the observation group was 96.88% (31/32) and the routine group was 78.13% (25/32), and the difference between the two groups was statistically significant ( χ2=5.14, P<0.05). Conclusions:The accelerated rehabilitation surgical nursing can effectively reduce the postoperative complications, the average length of stay, the average hospitalization expenses per case under DIP in patients with early cancer of digestive tract treated by ESD, improve the DIP allocation ratio of ESD diseases and the patient′s nursing satisfaction, which reflects the value of nursing work and can be applied to the nursing management of other surgical diseases.

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.

Objective:To investigate the appropriate pretreatment methods for single cell RNA sequencing of airway aspirate cells.Methods:Four fresh airway aspirate specimens were collected from four patients with acute respiratory tract infections. These specimens were digested with airway aspirate digester and prepared into single cell suspension. The cells were used for library construction directly (DE), or fixed with 10×Genomics Chromium Next GEM Single Cell Fixed RNA Sample Preparation Kit and then mixed to construct the library (DF), or cryopreserved, thawed, fixed (FF) before mixed to construct the library. All three methods were treated with oil emulsion using 10 4 cells and subjected to single-cell sequencing using the 10×Genomics platform. The number of obtained cells, data quality, annotated cell types and expression of marker genes were analyzed. Differences in the expression of highly variable genes (HVGs) of the same cell subsets obtained by the three pretreatment methods were compared using Pearson correlation. Expression of the differentially expressed genes in the same cell subpopulation obtained by different pretreatment methods was also compared. The correlation of the expression of differentially expressed genes between the same cell subsets obtained by the three pretreatment methods was analyzed by Pearson correlation. Results:The median numbers of single cells obtained using DE, FF and DF methods were 2 733, 1 140 and 5 897 ( P>0.05). The unique molecular identifiers were higher than 500. The median numbers of genes obtained using the three methods were 801, 887 and 1 259 ( P>0.05). The cells with novelty score over 0.8 accounted for 99%, 87% and 93%, respectively. There were nine cell subsets obtained by the three methods, including squamous cells, secretory cells, ciliated cells, T cells, B cells, macrophages, plasma cells and neutrophils. DF and FF methods could obtain more basal cells with specific high expression of keratin 5 than DE method. The differentially expressed and highly variable genes in the same cell subsets obtained by the three pretreatment methods showed high consistency in their expression with a significant correlation ( P<0.001). Conclusions:Under the same sequencing data volume, the quality of data obtained from fixed airway aspirate single-cell suspensions using the method of probe hybridization and transcriptome sequencing was comparable to that obtained directly from fresh cells. This method was more suitable for the pretreatment of clinical samples used for single-cell RNA sequencing.

Objective To investigate the value of endoscopic carbon nanoparticles labeling technique assisted in situ resection after neoadjuvant chemoradiotherapy(nCRT)for middle and low locally advanced rectal cancer(LARC).Methods From January 2020 to January 2023,46 cases of middle or low LARC were selected for endoscopic injection of carbon nanoparticles suspension to label the lower edge of the tumor before nCRT,and laparoscopic anterior resection of the rectum was performed after nCRT.The main observations were the visualization of carbon nanoparticles marker during the operation,the length of each area(primary tumor area,tumor regression scar,distal resection margin,and regression area of lower edge of tumor)of surgical specimens and the positive rate of distal resection margins.Results The median interval between injection of carbon nanoparticles suspension and surgery was 105(77-182)d in the46 cases.Carbon nanoparticles remnants were observed on the rectal mucosal surface in all the patients after nCRT by endoscopy.During laparoscopic anterior rectal resection surgeries,carbon nanoparticles marker exposure on the surface of the rectal intrinsic fascia observed in 41 cases(89.1%),of which38 cases were judged as good exposure(the width of marker area≤1.5 cm,which assisted the operator accurately determining the distal surgical margins)and 3 cases were judged as inferior exposure(a larger range of black staining whereas in situ resection of the tumor still achievable).In another 5 cases,the carbon nanoparticles marker could not be observed and were judged as exposure failure.Intraoperative cryopathology showed that all distal resection margins were negative.Measurement of 30 surgical specimens with identifiable primary tumor area showed that the length of resected intestinal canal was 17.9(10.1-25.7)cm,the diameter of primary tumor area was(4.3±0.8)cm,the diameter of scar after tumor regression was 2.5(0.8-4.8)cm,and the length of regression of tumor lower margin was 1.0(0-2.9)cm.The length of distal resection margins in middle rectal cancer(n =17)was3.4(1.5-4.3)cm and in low rectal cancer(n =13)was1.6(0.5-2.8)cm.Conclusion Application of carbon nanoparticles labeling technology before nCRT for rectal cancer can effectively mark the lower margin of the primary tumor in a long time and assist surgeons to precisely remove the primary tumor area.

Objectives:To explore the association between different blood pressure levels at baseline and early-onset heart disease among young adults under 40 years in China. Methods:This prospective cohort study included 35 993 subjects who participated in the physical examination of the employees of Kailuan Group for the first time from 2006 to 2012 and were younger than 40 years,with complete blood pressure data and had no history of heart disease.Participants were followed up to the end of 2021.The primary endpoint was early-onset heart disease(including coronary heart disease,atrial fibrillation,and heart failure).According to 2018 Chinese guidelines for the management of hypertension,the participants were divided into four groups:normal blood pressure group(n=13 208),elevated blood pressure group(n=16 576),stage 1 hypertension group(n=4 357),and stage 2-3 hypertension group(n=1 852).The cumulative incidence of heart disease among participants with different blood pressure levels at baseline was compared using log-rank test.Multivariate Cox proportional hazard regression model was used to analyze the impact of different blood pressure levels at baseline on early-onset heart disease in this cohort. Results:After a mean follow-up of(12.5±2.6)years,the cumulative incidence of early-onset heart disease in normal blood pressure group,elevated blood pressure group,stage 1 hypertension group,stage 2-3 hypertension group were 0.47%,0.97%,3.56%and 4.42%respectively(log-rank P<0.01).After adjusting for confounding factors such as age and sex,Cox regression analysis showed that the HR(95%CI)of heart disease in the elevated blood pressure group,hypertension grade 1 group and hypertension grade 2-3 group were 1.59(1.12-2.24),2.08(1.41-3.08)and 3.20(2.11-4.85)(all P<0.01),respectively,compared with the normal blood pressure group. Conclusions:Elevated blood pressure is a risk factor for early-onset heart disease among young Chinese population.

Objective:To apply the best evidence of pre-examination and triage management of patients with non-traumatic acute abdomen to clinical practice and evaluate its effects.Methods:Using convenience sampling method, 15 nurses and 237 patients with non-traumatic acute abdomen admitted in the emergency department of Shanxi Provincial People ′s Hospital from January to May 2021 were selected as the research objects, 114 cases as the baseline review group and 123 cases as the after-effect evaluation group. Following the clinical evidence practice application of JBI Evidence-Based Nursing Center Systematic standard procedures, using self before-after control study to compare the knowledge and behavior of triage nurses before and after evidence application, and compliance with each review index; using a non-contemporaneous controlled trial to compare the changes of pre-examination and triage time and triage accuracy between two groups. Results:After the application of evidence, the score of the triage nurses on the pre-examination and triage of non-traumatic acute abdomen increased from 98.00±6.56 in the after-effect evaluation group to 114.20±3.88 in the base-line review group, and the difference was statistically significant ( t=8.62, P<0.05); after the application of evidence, the compliance with indicators 1-9,12,13,15-17 was significantly improved and the difference was significant ( χ2 values were 11.46-123.06, all P <0.05). After the application of evidence, the compliance rate of those indicators <80% increased to more than 80% except indicator 6, the accuracy of patient triage rose from 84.21%(96/114) to 93.50%(115/123) with a statistically significant difference ( χ2=5.22, P<0.05); after the application of the evidence, the triage time was 2.00(1.00,4.00) min, shorter than 3.00(2.00,4.63) min in the base-line review group, and the difference was statistically significant ( Z=-3.18, P<0.05). Conclusions:The application of the best evidence of pre-examination and triage for non-traumatic acute abdomen can improve the nursing practice of non-traumatic acute abdomen triage, improve the accuracy of non-traumatic acute abdomen triage, and shorten the triage time.