Mitochondrial dysfunction in chondrocytes is a key pathogenic factor in osteoarthritis (OA), but directly modulating mitochondria in vivo remains a significant challenge. This study is the first to verify a correlation between mitochondrial dysfunction and the downregulation of the FOXO3 gene in the cartilage of OA patients, highlighting the potential for regulating mitophagy via FOXO3 gene modulation to alleviate OA. Consequently, we developed a chondrocyte-targeting CRISPR/Cas9-based FOXO3 gene-editing tool (FoxO3) and integrated it within a nanoengineered 'truck' (NETT, FoxO3-NETT). This was further encapsulated in injectable hydrogel microspheres (FoxO3-NETT@SMs) to harness the antioxidant properties of sodium alginate and the enhanced lubrication of hybrid exosomes. Collectively, these FoxO3-NETT@SMs successfully activate mitophagy and rebalance mitochondrial function in OA chondrocytes through the Foxo3 gene-modulated PINK1/Parkin pathway. As a result, FoxO3-NETT@SMs stimulate chondrocytes proliferation, migration, and ECM production in vitro, and effectively alleviate OA progression in vivo, demonstrating significant potential for clinical applications.

Objective To investigate the value of multiple quantitative parameters derived from Hawk spectral CT in predicting lymph node metastasis in papillary thyroid carcinoma(PTC).Methods Preoperative Hawk spectral CT images of 57 cancerous foci from 44 PTC patients confirmed by surgery and pathology were retrospectively collected.All patients underwent lymph node dissection.Based on pathological results,the patients were categorized into metastatic group(26 patients with 35 cancerous foci)and non-metastatic group(18 patients with 22 cancerous foci).The CT morphological features of the primary PTC lesions included location,diameter,bite-cookie sign,and calcification,respectively.Quantitative parameters of Hawk spectral CT plain scan,arterial phase(AP)and venous phase(VP),including conventional CT values,virtual monoenergetic imaging(MonoE)CT values(40 keV,100 keV),effective atomic number(Zeff)and electron density(Rho),respectively.The rank sum test or chi-square test was used to compare the differences in CT morphological features and Hawk spectral CT quantitative parameters between the two groups.For parameters with significant differences,logistic regression was used to construct a combined model.Area under the curve(AUC),accuracy,sensitivity,and specificity were used to evaluate the effectiveness of the combined model.Results There was statistically significant difference in the diameter of the primary lesion between the metastatic group and the non-metastatic group(P＜0.05),and the diameter of the primary lesion in the metastatic group was larger than that in the non-metastatic group.The conventional CT value,MonoE CT values(40 keV,100 keV),Rho and Zeff in plain scan,AP-Rho,and VP-MonoE CT value(100 keV)of the primary lesion in the metastatic group were all significantly lower than those in the non-metastatic group(P＜0.05).The AUC,accuracy,sensitivity and specificity of the Hawk spectral CT plain scan parameter combination model were 0.765,0.754,0.800,and 0.682,respectively.The AUC,accuracy,sensitivity,and specificity of the Hawk spectral CT enhancement parameter combination model were 0.726,0.667,0.600,and 0.786,respectively.Conclusion Through the analysis of multiple quantitative parameters from Hawk spectral CT of PTC primary lesion,the primary lesion in the metastatic group exhibited significant differences from those in the non-metastatic group in multiple quantitative parameters,which can further improve the predictive efficacy for lymph node metastasis.

Objective To evaluate the inhibitory effects of prophylactic administration of α-zearalanol(α-ZAL)on bone microarchitecture and bone resorption activity in ovariectomized osteoporotic rats,and to investigate its regulatory effects on the osteogenic and adipogenic differentiation of bone marrow mesenchymal stem cells(BMSCs).Methods A total of 606-month-old unmated female Sprague-Dawley(SD)rats weighing(300±20)g were randomly divided into the sham surgery group(Sham group),ovariectomy group(OVX group),solvent group(Oil group),estradiol benzoate treatment group(Post-E2 group),α-ZAL prevention group(Pre-ZAL group),and α-ZAL treatment group(Post-ZAL group),with 10 rats in each group.An osteoporosis rat model was established using the ovariectomy method.Rats in the Sham group underwent the same surgical procedures except for ovarian removal.Seventy-two hours after ovarian removal,the Oil group received intramuscular injections of 0.5 mL of oil solvent,and the Pre-ZAL group received intramuscular injections of α-ZAL(1.5 mg·kg-1),administered every 3 days for 120 consecutive days.The Post-E2 group and Post-ZAL group began intramuscular injections of estradiol benzoate(1.5 mg·kg-1)and α-ZAL(1.5 mg·kg-1),respectively,90 days after ovariectomy,administered every 3 days for 120 consecutive days.After drug administration,bone density and bone tissue microstructure morphology were analyzed using a micro-CT small animal in vivo imaging system and staining methods.Osteoclasts were isolated and their activity was detected.Femoral BMSCs were obtained to assess their osteoblast and adipocyte differentiation capabilities,and uterine tissue morphological changes were observed via histological sections.Results Compared with the OVX group,BMD in the Sham group,Post-E2 group,Pre-ZAL group,and Post-ZAL group increased by 133.12%,75.97%,69.64%,and 24.69%,respectively(all P<0.01).BMD in the Pre-ZAL group was 36.09%higher than in the Post-ZAL group(P<0.01),and there was no significant difference in BMD between the Post-E2 and Pre-ZAL groups(P>0.05).Tb.N in the Sham group,Post-E2 group,Pre-ZAL group,and Post-ZAL group increased by 160.08%,118.14%,94.76%,and 46.76%,respectively,compared with the OVX group(all P<0.01).Tb.Ar increased by 324.21%,203.83%,177.99%,and 82.71%,respectively(all P<0.01).Tb.N in the Pre-ZAL group increased by 32.71%compared to the Post-ZAL group(P<0.05),while Tb.Ar increased by 52.15%(P<0.01).Tb.Sp in the Sham,Post-E2,and Pre-ZAL groups decreased by 58.53%,42.18%,and 35.61%,respectively,compared with the OVX group(all P<0.01).The MAR of the upper tibial cancellous bone in the Sham,Post-E2,and Pre-ZAL groups increased by 257.81%,156.72%,and 142.63%,respectively,compared with the OVX group(all P<0.01),BFR increased by 192.19%,137.23%,and 88.13%,respectively(all P<0.01).MAR and BFR in the Pre-ZAL group increased by 58.10%and 43.63%,respectively,compared with the Post-ZAL group(both P<0.01).There were no significant differences in MAR and BFR between the Post-E2 group and the Pre-ZAL group(P>0.05).MMP-9,TRAP,and CK mRNA expression was significantly downregulated in both the Post-E2 group and the Pre-ZAL group(P<0.01).The osteoblast differentiation capacity of BMSCs in the Post-E2 group and all Post-ZAL groups was enhanced,with a significant increase in the number of mineralized nodules,and the expression levels of OCN,COL1,and OPN mRNA were significantly increased(P<0.01),while the ability to differentiate into adipocytes was weakened.The number of intracellular lipid droplets in BMSCs was significantly reduced,the lipid droplet volume was smaller,and the expression levels of PPAR-γ2 and aP2 mRNA were decreased(P<0.05).There were no significant differences between the Post-E2 group and the Pre-ZAL group(P>0.05).There was no significant increase in body weight in the Post-E2,Pre-ZAL,and Post-ZAL groups,but uterine weight significantly increased in the Post-E2 group(P<0.05),with marked uterine epithelial hyperplasia.Uterine weight in the Pre-ZAL and Post-ZAL groups showed no significant difference compared to the OVX group(P>0.05),and no significant changes were observed in uterine epithelium.Conclusion α-ZAL can effectively protect bone mass,improve bone microstructure,and reduce estrogen-related uterine adverse reactions by regulating the osteogenic/adipogenic differentiation balance of BMSCs,providing a potential new therapeutic strategy for the prevention and treatment of postmenopausal osteoporosis.

Objective To investigate the value of multiple quantitative parameters derived from Hawk spectral CT in predicting lymph node metastasis in papillary thyroid carcinoma(PTC).Methods Preoperative Hawk spectral CT images of 57 cancerous foci from 44 PTC patients confirmed by surgery and pathology were retrospectively collected.All patients underwent lymph node dissection.Based on pathological results,the patients were categorized into metastatic group(26 patients with 35 cancerous foci)and non-metastatic group(18 patients with 22 cancerous foci).The CT morphological features of the primary PTC lesions included location,diameter,bite-cookie sign,and calcification,respectively.Quantitative parameters of Hawk spectral CT plain scan,arterial phase(AP)and venous phase(VP),including conventional CT values,virtual monoenergetic imaging(MonoE)CT values(40 keV,100 keV),effective atomic number(Zeff)and electron density(Rho),respectively.The rank sum test or chi-square test was used to compare the differences in CT morphological features and Hawk spectral CT quantitative parameters between the two groups.For parameters with significant differences,logistic regression was used to construct a combined model.Area under the curve(AUC),accuracy,sensitivity,and specificity were used to evaluate the effectiveness of the combined model.Results There was statistically significant difference in the diameter of the primary lesion between the metastatic group and the non-metastatic group(P＜0.05),and the diameter of the primary lesion in the metastatic group was larger than that in the non-metastatic group.The conventional CT value,MonoE CT values(40 keV,100 keV),Rho and Zeff in plain scan,AP-Rho,and VP-MonoE CT value(100 keV)of the primary lesion in the metastatic group were all significantly lower than those in the non-metastatic group(P＜0.05).The AUC,accuracy,sensitivity and specificity of the Hawk spectral CT plain scan parameter combination model were 0.765,0.754,0.800,and 0.682,respectively.The AUC,accuracy,sensitivity,and specificity of the Hawk spectral CT enhancement parameter combination model were 0.726,0.667,0.600,and 0.786,respectively.Conclusion Through the analysis of multiple quantitative parameters from Hawk spectral CT of PTC primary lesion,the primary lesion in the metastatic group exhibited significant differences from those in the non-metastatic group in multiple quantitative parameters,which can further improve the predictive efficacy for lymph node metastasis.

OBJECTIVE To prepare reactive oxygen species(ROS)-responsive methotrexate(MTX)-modified paclitaxel(PTX)/icariin(ICA)micelles(MTX-oxi-Ms@PTX/ICA),and perform technology optimization and in vitro anti-tumor effect evaluation.METHODS Synergistic toxicity concentration range of PTX and ICA was screened by synergistic toxicity test.The micelles were prepared by thin film hydration method,and their technology was optimized by response surface methodology.The fundamental characteristics of the micelles prepared by the optimal technology were evaluated.The micelles'cytotoxicity,targeting ability to renal carcinoma RENCA cells of mice,and their inhibitory effects on invasion and migration were assessed.RESULTS Results of synergistic toxicity experiments demonstrated that the strongest synergistic effect occurred when PTX concentrations ranged from 2.5 to 10 μmol/L and ICA concentrations ranged from 5 to 15 μmol/L.The optimal technology of MTX-oxi-Ms@PTX/ICA was determined to include 80 mg Soluplus?,Soluplus? and TPGS1000 mass ratio of 4:1(mg/mg),2 mg DSPE-PEG2000-TK-PEG5000,2 mg DSPE-PEG2000-MTX,1 mg PTX,and 1.5 mg ICA,with a hydration temperature of 35 ℃ and a formulation volume of 5 mL.Under the optimal conditions,average encapsulation efficiency of PTX and ICA in 3 batches of MTX-oxi-Ms@PTX/ICA reached 92.75％,the critical micelle concentration(CMC)was 0.007 9 mg/mL,the particle size was(62.09±1.68)nm,the polydispersity index(PDI)was 0.046±0.032,and the Zeta potential was(-2.47±0.15)mV.Within 30 days of placement,there was no significant change in particle size and polydispersity index of micelle.In vitro release experiments showed that MTX-oxi-Ms@PTX/ICA released drugs more rapidly in oxidative environments.The half maximal inhibitory concentration of MTX-oxi-Ms@PTX/ICA against RENCA cells was(5.170±0.036)μmol/L.In vitro cellular uptake experiments indicated that compared with unmodified micelles,MTX modified micelles had stronger targeting effects on cancer cells,and also significantly enhanced the inhibitory ability of invasion and migration of RENCA cells(P＜0.05).CONCLUSIONS MTX-oxi-Ms@PTX/ICA micelles are successfully prepared,which exhibit high encapsulation efficiency,low critical micelle concentration,and good stability.These micelles demonstrate significant cytotoxicity against RENCA cells and effectively inhibit cancer cell invasion and migration.

Objective:To investigate the effects of repetitive transcranial magnetic stimulation (rTMS) on learning-memory and the expression of synaptic plasticity proteins in hippocampus of rats with post-stroke sleep deprivation.Methods:A total of 28 SPF grade healthy male Wistar rats with 8-week old were randomly divided into four groups (control group, sham operation group, model group and rTMS group) according to random number table method, with 7 rats in each group. The rats in the model group and the rTMS group were treated with middle cerebral artery occlusion and p-chlorophenylalanine intraperitoneal injection to establish the post-stroke sleep deprivation model. The rats in the rTMS group were treated with rTMS intervention for consecutive 14 days after modeling. The rats in the sham operation group were only separated arteries but not ligated and inserted. The rats in control group were fed normally. The open field test (OFT) was used to observe the autonomous behavior of rats.The water maze test(WMT) was used to observe the spatial learning and memory ability of rats.The content of tyrosine kinase receptor type B(TrkB) in hippocampus was detected by Western blot.The expressions of brain-derived neurotrophic factor(BDNF) and immediate early gene c-fos in hippocampus were detected by immunofluorescence.The morphology and structure of neurons in hippocampus were observed by optical microscopy and transmission electron microscopy. SPSS 21.0 software was used for statistical analysis, and repeated measurement ANOVA was used for the escape latency data, one-way ANOVA was used for the comparison of other data among multiple groups, and LSD test was used for further pairwise comparison.Results:(1) The OFT results showed that there were statistical differences in the numbers of crossing squares, upright times and total points of rats in the four groups after intervention ( F=27.638, 10.425, 30.690, all P<0.001). The numbers of crossing squares ((72.71±10.10)), upright times ((6.57±0.87)times) and total points ((79.29±10.03) points) of rats in rTMS group were all higher than those in model group after intervention ((43.71±6.96), (3.43±0.65)times, (47.14±6.82)points) (all P<0.05). As for the escape latency of WMT among the four groups of rats, the interaction effect was not significant( F=1.108, P=0.37), and the time main effect( Ftime=27.295, Ptime<0.01) and group main effect ( Fgroup=8.691, Pgroup<0.01) were significant after rTMS intervention.On the 3rd and 4th day, the escape latency of rTMS group rats was lower than that of the model group (both P<0.01). There were statistically significant differences in the numbers of crossing platform, swimming distance and residence time in target quadrant of rats in the four groups after intervention( F=8.569, 3.308, 3.547, all P<0.05). The numbers of crossing platform ((2.00±0.31)times), swimming distance in target quadrant ((196.95±24.57) cm) and residence time ((17.72±1.36)s) of rats in rTMS group were all higher than those in model group after intervention ((1.57±0.30)times, (146.61±4.79) cm, (13.58±0.98)s)(all P<0.05). (2)Optical microscopy and transmission electron microscopy showed that the hippocampal cells arranged irregularly, the organelles' integrity was destroyed in the model group compared with the normal control group. In rTMS group the arrangement and structure of nerve cells in the hippocampus were improved after rTMS intervention. (3) The immunofluorescence results showed that c-fos (1.49±0.09) and BDNF (0.84±0.06) in the hippocampus of rats in rTMS group were both higher than those in model group ((1.24±0.12), (0.48±0.08))(both P<0.05). The Western blot results showed that the expression level of TrkB (1.81±0.03) in the hippocampus of rats in rTMS group was higher than that in model group (0.96±0.02) ( P<0.05). Conclusion:The rTMS can improve the learning-memory ability and autonomous capacity of rats with post-stroke sleep deprivation, which may be related to promoting the expression of c-fos, BDNF and TrkB in hippocampus tissue.

With the widespread application of immunotherapy, the overall survival rate of lung cancer patients continues to improve, and the accompanying immune-related adverse events are increasingly valued, with cardiac toxicity being the most severe. Early identification and prevention of immunotherapy-related cardiac toxicity in lung cancer patients significantly improves their quality of life. This paper summarizes the early identification (risk factors, evaluation tools, and prediction models) and preventive measures of immunotherapy-related cardiac toxicity in lung cancer patients so as to provide a reference for the early identification, prevention, and management of immunotherapy-related cardiac toxicity in lung cancer patients.

Oncology cardiology is a rapidly developing field that requires innovative service designs to meet the growing demands of patients. Establishing the Oncology Cardiology Clinic is an important step in the history of cardiac oncology and a future trend. This paper describes the current development status of oncology cardiology at home and abroad, summarizes the experience of oncology cardiology management, so as to provide reference for the management of oncology cardiology in China.

Objective To investigate the effect and mechanism of long chain non-coding RNA(ln-cRNA)SNHG16 regulating PAR1 on the proliferation,migration and invasion of lung cancer.Methods From March 2020 to August 2021,lung cancer tissues and adjacent tissues of 35 patients with lung cancer were col-lected,and lung cancer cell lines(HCC827,A549,SK-LU-1,A427)and normal lung cell lines(MRC5)were simultaneously cultured.The overexpression model of PAR1(pcDNA-PAR1)was constructed by using the expression vector pcDNA3.1.A549 cells were divided into four groups after transfection:si-SNHG16,si-PAR1,si-SNHG16+pcDNA-PAR1 and control(transfection with si-NC).The expression levels of lncRNA SNHG16 and PAR1 in lung cancer cell lines(HCC827,A549,SK-LU-1,A427),lung cancer tissues and adja-cent tissues were detected by real-time fluorescence quantitative reverse transcription-polymerase chain reac-tion(qRT-PCR),and the transfection efficiency of each group was verified.MTT assay and clonal formation were used to determine the proliferation of cells in each group,flow cytometry was used to detect the apopto-sis of cells in each group,cell scratch and Transwell test were used to detect the migration and invasion ability of cells in each group,and Western blot was used to detect the protein expression of PAR1.Results The ex-pression level of lncRNA SNHG16 in lung cancer tissue was higher than that in adjacent tissues(P＜0.05).The expression level of lncRNA SNHG16 in lung cancer cell lines(HCC827,A549,SK-LU-1,A427)was higher than that in normal lung cell lines(MRC5),with statistical significance(P＜0.05).The results of qRT-PCR showed that the expression level of lncRNA SNHG16 gene was(21.02±0.04)％of the control af-ter transfection of si-SNHG16,the expression level of PAR1 gene was(19.06±0.02)％of the control after transfection of si-PAR1,and the expression level of PAR1 gene was 2.70±0.00 folds of the control after transfection of pcDNA-PAR 1,the difference was statistically significant(P＜0.05).The results of Western blot showed that the expression level of transfected in each PAR1 protein was different from that of the con-trol(P＜0.05).Compared with the control,the activity of cells transfected with si-SNHG16 was lower,the a-bility of clone formation,cell migration and invasion was obviously inhibited,and the apoptosis rate was higher(P＜0.05),while pcDNA-PAR1 could weaken the influence of transfected si-SNHG16 on cell proliferation,apoptosis,migration and invasion(P＜0.05).lncRNA SNHG16 was positively correlated with the expression level of PAR1(r=0.61).Conclusion lncRNA SNHG16 can regulate the occurrence and development of lung cancer by targeting PAR1.

Objective:To explore the effect of simulated gas of thermobaric bomb charge explosion on cognitive function and the related mechanism of damage.Methods:In January 2022, thirty-two SPF rats were selected and randomly divided into control group, exposed group 1, 2 and 3 (the exposure time of the simulated gas of the explosion of the thermobaric bomb charge was 5 min, 10 min and 15 min, respectively) according to random number table method, with 8 rats in each group. The simulated gas of the explosion of the thermobaric bomb charge were CO 0.15%, CO 2 3%, NO 0.1%, O 2 15%, and the rest were N 2. After 30 days of exposure, water maze was used to detect the learning and memory function of rats. Golgi staining was used to observe the number distribution and morphological structure of hippocampal neurons in rats. Western blot was used to detect the expression of Tau-5, pSer262, pSer396, pThr181 and pThr231 proteins in rats. Repeated measure ANOVA was used to compare the design data of repeated measure, one-way ANOVA was used for multi-group mean comparison, and LSD method was used for pound-wise comparison. Results:There were significant differences in the results of repeated measurement ANOVA of the water maze localization navigation test ( F=80.98, P<0.001), and there was an interaction between the group and the training days ( F=2.16, P=0.022). There were significant differences in escape latency of rats at the 2nd, 3rd, 4th and 5th days among all groups ( P<0.05). The results of spatial exploration showed that the frequency of rats crossing the platform was significantly different among all groups ( F=4.49, P=0.011). The frequency of rats crossing the platform in exposed group 2 and exposed group 3 was lower than that in control group, and the frequency of rats crossing the platform in exposed group 3 was lower than that in exposed group 1 ( P<0.05). With the increase of exposure time, the number of hippocampal neurons decreased, and the dendrite spine density of neurons in CA1 region decreased ( P<0.05). Compared with the control group, there was no significant difference in the relative expression level of Tau-5 protein in all exposed groups ( P>0.05), but the expression level of pSer262 protein was significantly increased ( P<0.05). Compared with the control group, the protein expressions of pSer396, pThr181 and pThr231 in exposed group 2 and exposed group 3 were significantly increased ( P<0.05) . Conclusion:The simulated gas of the explosion of the thermobaric bomb charge may contribute to the development of cognitive dysfunction by damaging hippocampal neurons with aberrant phosphorylation of Tau proteins.