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.

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 value of CT value in differential diagnosis of benign and malignant thyroid calcification.Methods The CT plain scan data of 48 cases of thyroid benign calcification and 26 cases of thyroid malignant calcification confirmed by pathology were analyzed retrospectively,and the CT values of 74 cases of thyroid calcification were measured.The best threshold and the maximum area under the receiver operator characteristic(ROC)curve for differentiating benign and malignant thyroid calcification were determined by plotting ROC curve,and the corresponding specificity,sensitivity,positive predictive value,negative predictive value,false positive rate,false negative rate,accuracy and Jordan index were calculated.Then the optimal threshold value was used as a parameter for differential diagnosis of benign and malignant thyroid calcification,and we adoptted χ2 analyze the statistical difference between benign and malignant thyroid calcification in CT gray value.Results The area under the ROC curve was 0.814,and the 95%confidence interval(CI)was 0.712-0.915.When the CT value was 869.5HU(for the convenience of 870HU),the specificity was 69.2%,the sensitivity was 81.3%,the positive predictive value was 64.3%,the negative predictive value was 82.6%,the false positive rate was 20.8%,and the false negative rate was 30.8%,the accuracy was 75.7%and the maximum of the Youden index was 0.505.When 870HU was taken as the differential diagnosis parameter of thyroid benign and malignant calcification(χ2=16.795,P<0.001).Conclusion When the CT value is 870HU,it has important value in differential diagnosis of benign and malignant thyroid calcification.

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.

Tumor is a serious threat to human health. At present, surgical resection, chemoradiotherapy, targeted therapy and immunotherapy are the main therapeutic strategies. Monoclonal antibody has gradually become an indispensable drug type in the clinical treatment of cancer due to its high efficiency and low toxicity. Phage antibody library technology (PALT) is a novel monoclonal antibody preparation technique. The recombinant immunoglobulin variable region of heavy chain (VH)/variable region of light chain (VL) gene is integrated into the phage vector, and the antibody is expressed on the phage surface in the form of fusion protein to obtain a diverse antibody library. Through the process of adsorption-elution-amplification, the antibody library can be screened to obtain the antibody molecule with specific binding antigen as well as its gene sequence. PALT has the advantages of short antibody production cycle, strong plasticity of antibody structure, large antibody yield, high diversity and direct production of humanized antibodies. It has been used in screening tumor markers and preparation of antibody drugs for breast cancer, gastric cancer, lung cancer and liver cancer. This article reviews the recent progress and the application of PALT in tumor therapy.
Humans ; Bacteriophages/genetics* ; Immunoglobulin Variable Region/genetics* ; Gene Library ; Antibodies, Monoclonal/therapeutic use* ; Immunotherapy ; Peptide Library

The estimated new cases of breast cancer (BC) patients were 2.26 million in 2020, which accounted for 11.7% of all cancer patients, making it the most prevalent cancer worldwide. Early detection, diagnosis and treatment are crucial to reduce the mortality, and improve the prognosis of BC patients. Despite the widespread use of mammography screening as a tool for BC screening, the false positive, radiation, and overdiagnosis are still pressing issues that need to be addressed. Therefore, it is urgent to develop accessible, stable, and reliable biomarkers for non-invasive screening and diagnosis of BC. Recent studies indicated that the circulating tumor cell DNA (ctDNA), carcinoembryonic antigen (CEA), carbohydrate antigen 15-3 (CA15-3), extracellular vesicles (EV), circulating miRNAs and BRCA gene from blood, and the phospholipid, miRNAs, hypnone and hexadecane from urine, nipple aspirate fluid (NAF) and volatile organic compounds (VOCs) in exhaled gas were closely related to the early screening and diagnosis of BC. This review summarizes the advances of the above biomarkers in the early screening and diagnosis of BC.
Humans ; Female ; Biomarkers, Tumor ; Early Detection of Cancer ; Breast Neoplasms/diagnosis* ; Prognosis ; MicroRNAs/genetics*

Objective:To investigate the expressions and clinical significance of tetraspanin CO-029 and integrin αv in intrahepatic cholangiocarcinoma (ICC ).Methods:Tissue microarray (TMA) was used to detect the expression of CO-029 and αv in 254 cases of intrahepatic cholangiocarcinoma. The relationship between the two factors and clinicopathological features, recurrence, metastasis and prognosis was analyzed.Spearman method was used to analyze their correlation.Relationship between αv and CO-029 was studied by mass spectrometry and database search,immunoprecipitation and Western blot were used to detect the coexistence.Results:Tissue microarray analysis showed that the positive expression rate of CO-029 was 51.6% (131/254), and the positive expression rate of αv was 61.4% (156/254). The expression of CO-029 and αv were closely correlated with tumor envelope, size, number and TNM stage ( P<0.05). According to the time of recurrence (TTR), the expressions of CO-029 and αv in early postoperative recurrence group (TTR <1 year) were significantly higher than those in non recurrence group (TTR ≥ 1 year). The patients with high CO-029 expression were more likely to relapse ( HR=2.01, 95% CI=1.45-2.79; P<0.001) and had shorter survival time ( HR=2.03, 95% CI=1.46-2.81; P<0.001). The patients with high expression of αv had shorter recurrence time ( HR=1.85, 95% CI=1.38-2.47; P<0.001) and shorter survival time ( HR=1.95, 95% CI=1.40-2.71; P<0.001). Co immunoprecipitation and Western blot confirmed that αv and CO-029 formed a complex. There was a positive correlation between CO-029 and αv in intrahepatic cholangiocarcinoma ( r=0.401, P<0.01). Conclusions:The differential expression of CO-029 and αv were closely related to the recurrence, metastasis and prognosis of intrahepatic cholangiocarcinoma, and CO-029 may couple with αv to form a complex to promote the invasion and metastasis of intrahepatic cholangiocarcinoma.

Current advances of immunotherapy have greatly changed the way of cancer treatment. At the same time, a great number of nanoparticle-based cancer immunotherapies (NBCIs) have also been explored to elicit potent immune responses against tumors. However, few NBCIs are nearly in the clinical trial which is mainly ascribed to a lack understanding of

Objective:Retrospective analysis of the epidemiological and clinical characteristics of the novel coronavirus pneumonia (COVID-19) in children, to provide suggestions for the clinical diagnosis and treatment of children infected with SARS-CoV-2.Methods:7 COVID-19 children admitted to Xiangyang Central Hospital from January to February 2020 were studied. The epidemiological, clinical, laboratory, radiological characteristics and disease outcome data were obtained from data collection forms and electronic medical records.Results:Among the 7 children, 3 were male and 4 were female, median age was 8 years (2.6-14.0), 2 patients with co-morbidities , 4 patients with family aggregation history, two of them are brothers and sisters, all of the 7 children had a history of high-risk epidemiology. The main clinical symptoms of children with COVID-19 were fever (4 cases), cough and expectoration (5 cases), whereas others were asymptomatic (2 cases). The peripheral blood manifestations of the patients were as follows: abnormal leukocyte count was observed in 1 case, decrease of neutrophil was observed in 2 cases , 1 case with increase of C-reactive protein (CRP) and 3 cases with increase of lactate dehydrogenase, other indexes like the lymphocyte count was normal in all patients. There were no significant changes in serum albumin, AST, CK and SCR in children. Most of the chest CT findings of children were high density lesions of lung lobes, 2 of them had typical ground glass density shadow. The clinical types of 5 children were common type and the rest are subclinical type. All cases were cured by antiviral plus symptomatic treatment(Arbidol), and combination of traditional Chinese medicine prescription treatment.Conclusion:Children COVID-19 were mainly mild and common cases, most of them were familial clusters, the laboratory examination showed no specificity and their prognosis was well.

Objective To compare the effects of nicorandil and trimetazidine on endothelial function and inflammatory cytokines in patients with coronary heart disease after percutaneous coronary intervention (PCI),and to analyze the synergistic effect .Methods 160 patients with coronary heart disease underwent elective PCI were enrolled and randomly divided into four groups ,40cases in each group .The nicorandil group was given nicorandil tab-lets 5mg once time,3 times a day at 72h before PCI.The trimeshamazine group was given trimetazidine tablets 20mg once time,3 times a day.The combined group was given the same dose of nicorandil and trimetazidine .The control group was not given nicorandil or trimetazidine .The changes of CK -MB,cTnI,ET-1,NO,hs-CRP,TNF-αand IL-6 were observed and compared before and after PCI .Results The CK-MB and cTnI in the control group were significantly increased after PCI (t=2.500,3.663,all P<0.05;t=4.168,5.783,4.912,all P<0.05),but there were no statistically significant differences in the other three groups (all P>0.05).The level of cTnI in the control group was higher than that in the other three groups after PCI (F=11.960,15.643,16.078,all P<0.05).After PCI,the levels of ET-1,hs-CRP,TNF-αand IL-6 in the four groups were all significantly increased ( control group:t=6.897,5.293,all P<0.05;t=15.934,16.759,all P<0.05;t=8.516,9.209,all P<0.05;t=6.809, 6.757,all P<0.05;nicorandil group:t=2.254,P<0.05;t=8.903,11.280,all P<0.05;t=5.961,5.992,all P<0.05;t=4.235,4.738,all P<0.05;trimetazidine group:t=3.425,P<0.05;t=10.513,11.582,all P<0.05;t=4.117,5.696,all P<0.05;t =4.130,3.868,all P<0.05;combination group:t =3.180,P<0.05;t =9.204, 10.107,all P<0.05;t=4.839,6.214,all P<0.05;t=5.151,5.883,all P<0.05),and NO level was significantly decreased(control group:t=5.707,5.066,all P<0.05;nicorandil group:t=2.701,2.393,all P<0.05;trimetazi-dine group:t=3.662,3.163,all P<0.05;combination group:t=2.632,2.427,all P<0.05).The levels of ET-1, hs-CRP,TNF-αand IL-6 in the control group were significantly higher than those in the other three groups after PCI(F=9.709,7.794,P<0.05;F=43.772,47.321,P<0.05;F=15.252,10.565,P<0.05;F=5.632,4.372, P<0.05),and NO level in the control group was lower than that in the other three groups (F=14.138,8.374,all P<0.05).The level of NO in the nicorandil group was higher than that in the trimetazidine group (t=2.249,2.305, all P<0.05).There was no synergistic effect between nicorandil and trimetazidine in improving ET -1,NO,hs-CRP,TNF-αor IL-6(P>0.05).Conclusion Both nicorandil and trimetazidine may help to relieve PCI -related myocardial injury , improve endothelial function , inhibit inflammatory factors after PCI , but there is no synergistic effect.Nicorandil may be more effective in improving endothelial function .