BACKGROUND:The exact pathogenesis of temporomandibular joint osteoarthritis is currently unclear.Traditional clinical treatment strategies for temporomandibular joint osteoarthritis are symptomatic treatments such as pain relief and reduction of inflammation,which can stop the progression of the disease to a certain degree but cannot reverse the destruction of the cartilage.Cartilage degeneration,as one of the most prominent pathologic features in the development of temporomandibular joint osteoarthritis,has been the subject of an increasing number of studies that focus on its pathogenesis.Consequently,we hope to provide an ideal radical solution for the regeneration of the temporomandibular joint.OBJECTIVE:To review the progress of research on cartilage degeneration in temporomandibular joint osteoarthritis.METHODS:The search terms were"temporomandibular joint osteoarthritis,degradation of cartilage matrix,synovitis,oxidative stress,chondrocyte hypertrophy,chondrocyte apoptosis,ferroptosis,autophagy,angiogenesis,extracellular vesicles"in Chinese and English.Literature search was conducted in PubMed database and CNKI,and the time limit for the search was from January 2004 to October 2024.Screening was performed by analyzing and reading the literature,and according to the inclusion and exclusion criteria,81 papers were finally included for review.RESULTS AND CONCLUSION:(1)Increased secretion of cartilage matrix degrading enzymes causes degradation of the cartilage matrix,leading to cartilage degeneration.(2)Synovitis promotes cartilage degeneration through macrophage M1-type polarization and production of inflammatory mediators.(3)Oxidative stress promotes cartilage degeneration by exacerbating the inflammatory response through overproduction of reactive oxygen species.(4)Chondrocyte phenotypic changes and death lead to the decrease of cartilage matrix synthesis,resulting in cartilage degeneration.(5)Blood vessels of subchondral bone penetrate the calcified cartilage layer to reach the superficial cartilage layer,which destroys the cartilage structure and leads to cartilage degeneration.(6)Bioactive substances carried by serum-derived extracellular vesicles in inflammatory states also promote cartilage degeneration in temporomandibular joint osteoarthritis.

BACKGROUND:The exact pathogenesis of temporomandibular joint osteoarthritis is currently unclear.Traditional clinical treatment strategies for temporomandibular joint osteoarthritis are symptomatic treatments such as pain relief and reduction of inflammation,which can stop the progression of the disease to a certain degree but cannot reverse the destruction of the cartilage.Cartilage degeneration,as one of the most prominent pathologic features in the development of temporomandibular joint osteoarthritis,has been the subject of an increasing number of studies that focus on its pathogenesis.Consequently,we hope to provide an ideal radical solution for the regeneration of the temporomandibular joint.OBJECTIVE:To review the progress of research on cartilage degeneration in temporomandibular joint osteoarthritis.METHODS:The search terms were"temporomandibular joint osteoarthritis,degradation of cartilage matrix,synovitis,oxidative stress,chondrocyte hypertrophy,chondrocyte apoptosis,ferroptosis,autophagy,angiogenesis,extracellular vesicles"in Chinese and English.Literature search was conducted in PubMed database and CNKI,and the time limit for the search was from January 2004 to October 2024.Screening was performed by analyzing and reading the literature,and according to the inclusion and exclusion criteria,81 papers were finally included for review.RESULTS AND CONCLUSION:(1)Increased secretion of cartilage matrix degrading enzymes causes degradation of the cartilage matrix,leading to cartilage degeneration.(2)Synovitis promotes cartilage degeneration through macrophage M1-type polarization and production of inflammatory mediators.(3)Oxidative stress promotes cartilage degeneration by exacerbating the inflammatory response through overproduction of reactive oxygen species.(4)Chondrocyte phenotypic changes and death lead to the decrease of cartilage matrix synthesis,resulting in cartilage degeneration.(5)Blood vessels of subchondral bone penetrate the calcified cartilage layer to reach the superficial cartilage layer,which destroys the cartilage structure and leads to cartilage degeneration.(6)Bioactive substances carried by serum-derived extracellular vesicles in inflammatory states also promote cartilage degeneration in temporomandibular joint osteoarthritis.

ObjectiveTo investigate the relationship between the vasodilation and hydrogen sulfide （H₂S） mechanism of total flavonoids of chrysanthemum （TFCC） and the large conductance Ca²⁺- activated K⁺ （BK_Ca） channels on vascular smooth muscle cells （VSMCs） of the middle cerebral artery in rats. In addition， this study will also investigate the effect of TFCC on the expression of BK_Ca channel alpha protein in rat middle cerebral artery VSMCs. MethodsThe primary method employed was acute digestion to isolate VSMCs from the middle cerebral artery of rats； whole-cell patch-clamp techniques were used to measure BK_Ca channel currents； primary tissue adherence culture was utilized to cultivate VSMCs from the middle cerebral artery of rats； Western blot were employed to determine protein expression levels. ResultsIn whole-cell patch-clamp experiments， both the H₂S donor NaHS （100 μmol/L） and endogenous H₂S enhanced BK_Ca channel currents. TFCC （30， 90， and 270 mg/L） also activatedBK_Ca channels and exhibited a certain concentration-dependent effect. Even after blocking endogenous H₂S production， TFCC （270 mg/L） still activated BK_Ca channels in VSMCs of the middle cerebral artery in rats. In Western blot experiments， the α-subunit of BK_Ca channel proteins was expressed in all groups of cells， but TFCC （30， 90， and 270 mg/L） and inhibitor IBTX group did not affect the expression of channel protein content.Conclusion TFCC can promote the opening of BK_Ca channels by promoting the generation of endogenous H₂S， or directly activate BK_Ca channels， thereby playing a role in relaxing cerebral blood vessels. However， TFCC had no significant effect on the expression of BK_Ca channel proteins.

ObjectiveTo investigate the associations of multiple glycolipid metabolic indicators and their cumulative abnormality burden with incident colorectal cancer risk in a general population-based prospective cohort, and to examine the mediating role of glycolipid metabolic abnormalities in the relationships between smoking, alcohol consumption, physical activity, and colorectal cancer incidence. MethodsA total of 17 897 eligible participants recruited from the Taizhou Cohort between 2011 and 2014 were included. Cox proportional hazards regression models were used to assess the associations of conventional and derived glycolipid indicators, as well as a glycolipid abnormality index constructed from total cholesterol, triglycerides, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, fasting plasma glucose, and insulin, with incident colorectal cancer risk. Restricted cubic spline models were applied to evaluate dose-response relationships for major indicators. Receiver operating characteristic curves were generated to compare predictive performance across indicators. Mediation analyses were conducted to assess the mediating effects of the glycolipid abnormality index on the associations of smoking, alcohol consumption, and physical activity with colorectal cancer incidence. ResultsDuring a median follow-up of 11.2 years, 102 incident colorectal cancer cases were identified, with an incidence density of 51.2 per 100 000 person-years. After adjustment for potential confounders, Cox proportional hazards regression analyses showed that decreased high-density lipoprotein cholesterol was associated with a 1.74-fold higher risk of colorectal cancer (HR=1.74, 95%CI: 1.03‒2.95), elevated low-density lipoprotein cholesterol was associated with a 1.78-fold higher risk (HR=1.78, 95%CI: 1.05‒3.02), and abnormal fasting plasma glucose was associated with a 1.86-fold higher risk (HR=1.86, 95%CI: 1.15‒3.02). Triglycerides and fasting plasma glucose showed an approximately linear increasing association with colorectal cancer risk in multivariable restricted cubic spline models. The glycolipid abnormality index showed a clear gradient association with colorectal cancer risk; participants with three or more abnormal indicators had a 3.08-fold higher risk than those without abnormalities (HR=3.08, 95%CI: 1.60‒5.92). The area under the curve was 0.795, higher than that of individual glycolipid indicators and other combined indices, and gender-stratified analyses showed generally consistent patterns. Glycolipid metabolic abnormalities partially mediated the associations of smoking, alcohol consumption, and physical activity with colorectal cancer incidence, with mediation proportions of 8.33%, 9.45%, and 9.04%, respectively. ConclusionGlycolipid metabolic abnormalities are associated with an increased risk of incident colorectal cancer. The glycolipid abnormality index shows an increasing relationship with colorectal cancer risk and demonstrates better discrimination, and it partially mediates the associations of smoking, alcohol consumption, and physical activity with colorectal cancer incidence in the overall population.

Objective:To investigate the effect of nuclear receptor subfamily 2 group F member 2(NR2F2)on the biological behaviors of human ovarian cancer SKOV3 cells,and to clarify its molecular mechauism and provide the new idea for treatment of ovarian cancer.Methods:Gene Expression Profiling Interactive Analysis(GEPIA)Database analyse the expression level of NR2F2 gene in ovarian tissue,and analyse its correlation with clinical prognosis of ovarian cancer patients.The human ovarian cancer SKOV3 cells were divided into control group and NR2F2 over-expression(NR2F2 OE)group,which were transfected with mCherry control virus and NR2F2 OE over-expression virus,respectively,when the cell deusity reached 70％,and the stable transfection SKOV3 cell lines were screened with puromycin(puro)48h lafter.Real-time fluorescence quantitative PCR(RT-qPCR)and Western blotting methods were used to detect the transfection efficiencies of the cells;RT-qPCR method was used to detect the expression levels of NR2F2 and sex-determining region Y-box 2(SOX2)mRNA in the cells in two groups;Western blotting method was used to detect the expression levels of NR2F2,ATP-binding cassette superfamily G member 2(ABCG2),and programmed cell death 1-ligand 1(PD-L1)protcins in the cells in two groups.CCK-8 assay was used to detect the proliferation activities of the cells in two groups;Wound assay was used to detect the migration rates of the cells in two groups;Transwell chamber assay was used to detect the number of transmembrane cells;Spheroidization assay was used to detect the numbers of spheroids in the cells;peripheral blood mononuclear cells(PBMCs)-mediated tumor cell killing assay was used to detect the relative densities of surviving tumor cells;CCK-8 assay was used to detect the half maximal inhibitory concentration(IC50)of paclitaxel(PTX)and carboplatin(CBP).Results:Compared with normal ovarian tissue,the expression level of NR2F2 gene in ovarian tumor tissue was decreased(P＜0.05),and decreased with the improvement of clinical pathological grading of ovarian tumor.The patients with higher expression level of NR2F2 gene had better clincal prognosis.The SKOV3 cells with NR2F2 over-expresson were successfully constructed,and the expression levels of NR2F2 mRNA and protein in the cells in NR2F2 OE group were increased compared with control group(P＜0.001).The CCK-8 assay results showed that compared with control group,the proliferation activities of the cells in NR2F2 OE group were decreased at different time points(1,2,3,and 4 d)(P＜0.05 or P＜0.01).The cell wound assay results showed that compared with control group,the migration rate of the cells in NR2F2 OE group was decreased(P＜0.001).The Transwell assay results showed that compared with control group,the number of transmembrane cells in NR2F2 OE group was decreased(P＜0.01).Compared with control group,the number of the spheroids in NR2F2 OE group was decreased(P＜0.05),and the expression levels of SOX2 mRNA(P＜0.01)and protein(P＜0.001)were increased.Compared with control group,the relative density of surviving tumor cells in NR2F2 OE group was decreased,but the difference was not significant(P＜0.05),and the expression level of PD-L1 protein was decreased(P＜0.05).Compared with control group,the proliferation activities of cells in NR2F2 OE group were decreased(P＜0.05),and the drug sensitivities of the cells to PTX and CBP were enhanced(P＜0.05);the IC50 of PTX was significantly reduced,while the IC50of CBP could not be calculated due to excessively high drug concentration;the expression level of ABCG2 protein was decreased(P＜0.05).Conclusion:The over-expression of NR2F2 may inhibit the proliferation,migration,and invasion of the human ovarian cancer SKOV3 cells,decrease the expression levels of SOX2,PD-L1 and ABCG2 proteins,suppress the stemness and immune evasion ability of the SKOV3 cells,and enhance the sensitivities of the SKOV3 cells to PTX and CBP.

OBJECTIVE Aimed to construct a corpus for a developing auditory-verbal communication training system tailored for the elderly and to grade the difficulty of sentence materials.The ultimate goal is to meet the diverse needs of trainees with varying hearing and speech capabilities.METHODS A training corpus,encompassing 3 627 sentences across 12 distinct topics,was systematically established.During the pre-experimental phase,12 adult subjects with normal hearing were recruited.They were tasked with conducting speech recognition rate tests on 100 randomly selected test sentences under four different signal-to-noise ratio(SNR)conditions.By plotting the performance-intensity(P-I)function curve,the SNR50 value,specifically-6.5 dB,was accurately determined.In the formal experiment,17 additional subjects were recruited.All sentences within the corpus were then subjected to speech recognition rate tests in a noisy environment under the established SNR50 condition.The average recognition rate was computed,and both the recognition rate-frequency histogram and the normal distribution curve were plotted.Leveraging the area beneath the normal curve,the segmentation points of the speech recognition rate were calculated,enabling the classification of sentences into three difficulty levels:easy,medium,and difficult.RESULTS The task of classifying the difficulty of sentences within the corpus was successfully accomplished.Specifically,there were 1 144 easy sentences,constituting 33%of the total;1 099 medium sentences,accounting for 32%;and 1 212 difficult sentences,representing 35%.CONCLUSION This research has successfully concluded the establishment of a corpus for the elderly's auditory-verbal communication ability training system and its associated difficulty grading.The obtained grading results are found to be in accordance with the principle of partitioning the difficulty gradient based on area.This study explores an effective method for grading the difficulty of auditory training sentences,ensuring that the training content matches the level of the trainer's competence.This not only enhances the training effectiveness but also improves the overall user experience.

A dielectric barrier discharge ionization source with rapid evaporation and self-aspiration sampling(RE-SADBDI)was developed,integrating a rapid evaporation(RE)module and a dielectric barrier discharge ionization(DBDI)module.The sample was introduced into the RE module via a sampling swab and rapidly vaporized within it.The sealed design of the ionization source could enable the sample to be self-aspirated into the ionization region without the need of additional inert gas.All vaporized sample was efficiently directed into the ionization region due to the relatively enclosed environment for sample transfer and ionization,resulting in improved transfer and ionization efficiencies.Experimental results showed that the limit of detection(LOD)under ion isolation mode reached 0.05 ng/mL(caffeine),with a relative standard deviation(RSD)of 6.9%.Furthermore,when coupled with a miniaturized linear ion trap mass spectrometer,the source enabled real-time analysis of various sample types.The developed RE-SADBDI source was suitable for on-site analysis with miniaturized mass spectrometers.

Objective:To compare the dose-response effects of single-fraction ultra-high dose rate (FLASH) and conventional dose rate (CONV) whole abdominal irradiation (WAI) with X-rays on acute radiation-induced intestinal injury in mice, in order to identify optimal dose parameters and potential mechanisms.Methods:A total of 186 male C57BL/6J mice were randomly assigned to a non-irradiation group ( n=6), FLASH irradiation groups ( n=90), and CONV irradiation groups ( n=90). Acute radiation-induced intestinal injury models were established using single-fraction WAI with 11, 12, 13, 14, and 15 Gy X-rays (200 Gy/s for FLASH and 4 Gy/min for CONV). Changes in body weight, stool characteristics, and disease activity index (DAI) scores were assessed at 9 d post-irradiation. At 7 d post-irradiation at 11, 12, and 13 Gy, the intestines were collected for macroscopic examination and length measurement. The small intestine was selected for HE staining and quantitative analysis of intestinal crypt number and mucosal epithelial thickness. The survival of mice was assessed at 15 d post-WAI across all dose groups. Results:After single-fraction WAI at 11, 12, and 13 Gy, the body weight was higher in the FLASH group than that in the CONV group ( t=10.17, 12.65, 10.16, P<0.05). The DAI scores for the FLASH group were 1.00±1.10, 3.17±0.75, and 2.83±1.17, respectively, which were lower than those of the CONV group (4.33±0.52, 7.00±0.00, 8.60±0.55; t=8.70, 11.71, 14.99, P<0.05). However, after WAI at 14 Gy and 15 Gy, there were no significant differences in body weight and DAI between the FLASH group and the CONV group ( P>0.05). At 7 d after single-fraction WAI at 11, 12, and 13 Gy, mice in the FLASH group exhibited less intestinal congestion, edema, and shortening compared with the CONV group. The difference between the FLASH and CONV groups were statistically significant in small intestine length at 11 and 13 Gy ( t=4.42, 3.78, P<0.05), and in colorectal length at 11 and 12 Gy ( t=3.97, 3.12, P<0.05). Small intestine HE staining revealed superior preservation of intestinal architecture in the FLASH group compared with the CONV group, characterized by longer villi, increased crypt numbers, thicker mucosal epithelium, and enhanced structural integrity. The differences in crypt number and mucosal epithelial thickness were statistically significant ( tcrypt=13.10, 23.80, 11.90; tmucosal=5.75, 2.64, 7.74; P<0.05). At 15 d post-irradiation, the survival rate in the 15 Gy FLASH group was higher than that in the CONV group (50% vs. 10%, χ2=5.39, P<0.05), with a median survival extension of 6 d ( HR=0.340, 95% CI: 0.115 4-0.999 9). No significant survival differences were observed between the FLASH group and the CONV group at 11, 12, 13, and 14 Gy ( P>0.05). Conclusions:FLASH irradiation significantly alleviated acute radiation-induced intestinal injury from medium single-fraction WAI with 11, 12, and 13 Gy X-rays compared with CONV irradiation, and showed potential to improve mouse survival after single-fraction WAI at 15 Gy. This effect is likely associated with the preservation of intestinal crypts and exhibits a dose-dependent relationship.

Aim To investigate the effects of total fla-vonoids of Chuzhou chrysanthemum(TFCC)on the activity and migration of rat brain artery endothelial cells under hypoxia/reoxygenation(H/R)injury,as well as the relationship between TFCC's effects and vascular endothelial growth factor receptor 2(VEGFR2).Methods Primary rat brain artery endo-thelial cells were cultured,the H/R model of cells was constructed,VEGFR2 inhibitor SU5416(10 μmol·L-1)was used and a cell transfection model was estab-lished.The cell activity was detected by CCK-8,and the cell migration was detected by scratch method and Transwell assay.Results TFCC(30,90,270 mg·L-1)significantly increased the activity and migration ability of rat brain artery endothelial cells with H/R in-jury,the use of VEGFR2 blocker SU5416 and transfec-tion of VEGFR2 siRNA could significantly inhibit the enhanced activity and migration ability of TFCC on cer-ebral vascular endothelial cells in rats with H/R inju-ry.Conclusions TFCC promotes the activity and mi-gration ability of rat brain artery endothelial cell with H/R injury,and its mechanism is related to VEGFR2.

Objective The optimum formulation process was selected to prepare the ethosomes of Cortex Dictamni-Fructus Kochiae,and its prescription was verified and its properties were studied.Methods The formulation was optimized by single factor and response surface test.The appearance,particle size,Zeta potential and stability were investigated.The encapsulation rate was used as the evaluation index.Results The optimum preparation process of ethosomes of Cortex Dictamni-Fructus Kochiae is as follows:Using the dosage of lyophilized powder 409.06 mg,soybean lecithin 258.07 mg,cholesterol 90.87 mg,ethanol volume fraction 22.76％,stirred for 2 hours at 700 r·min-1 at 50 ℃ water bath temperature,The appearance of the prepared ethosomes suspension was light yellow,and the particles were nearly spherical in shape.The average particle size was(103.1±0.78)nm,the Zeta potential was(-36.0±3.65)mV,and the average encapsulation rates of Xibutanone,ash,and saponin Ⅰc were(89.25±0.91)％,(80.16±1.52)％,(86.59±0.58)％,respectively.After 14 days of storage at room temperature,the results showed that:The ethosomal suspension is still a light yellow,uniform,and stable liquid,and there is no stratified precipitation phenomenon.Conclusion The method of ethanol injection is easy to operate,high encapsulation rate and good stability,which lays a foundation for further study on the skin administration of this preparation.