The ambiguity of etiology makes temporomandibular joint osteoarthritis (TMJOA) "difficult-to-treat". Emerging evidence underscores the therapeutic promise of exosomes in osteoarthritis management. Nonetheless, challenges such as low yields and insignificant efficacy of current exosome therapies necessitate significant advances. Addressing lower strontium (Sr) levels in arthritic synovial microenvironment, we studied the effect of Sr element on exosomes and miRNA selectively loading in synovial mesenchymal stem cells (SMSCs). Here, we developed an optimized system that boosts the yield of SMSC-derived exosomes (SMSC-EXOs) and improves their miRNA profiles with an elevated proportion of beneficial miRNAs, while reducing harmful ones by pretreating SMSCs with Sr. Compared to untreated SMSC-EXOs, Sr-pretreated SMSC-derived exosomes (Sr-SMSC-EXOs) demonstrated superior therapeutic efficacy by mitigating chondrocyte ferroptosis and reducing osteoclast-mediated joint pain in TMJOA. Our results illustrate Alix's crucial role in Sr-triggered miRNA loading, identifying miR-143-3p as a key anti-TMJOA exosomal component. Interestingly, this system is specifically oriented towards synovium-derived stem cells. The insight into trace element-driven, site-specific miRNA selectively loading in SMSC-EXOs proposes a promising therapeutic enhancement strategy for TMJOA.
MicroRNAs/metabolism* ; Mesenchymal Stem Cells/drug effects* ; Osteoarthritis/drug therapy* ; Exosomes/drug effects* ; Strontium/pharmacology* ; Synovial Membrane/cytology* ; Humans ; Animals ; Temporomandibular Joint Disorders/therapy* ; Temporomandibular Joint

Aiming at the problems of tongue diagnosis instruments relying on manual operation,uneven illumination,color distortion and lack of dynamic information,an automated operation black box tongue diagnosis instrument based on machine vision is proposed.This instrument utilizes machine vision technology and image processing algorithms to achieve automatic positioning and automatic acquisition of tongue manifestations.High-resolution camera technology enables the acquisition of 3-second dynamic videos and high-quality static images.The performance test results show that,based on the dual-camera geometric projection calibration algorithm,the average time for tongue recognition is less than 0.15 seconds.The diffuse reflection light source improves the gray uniformity to 76.74%,and the maximum color difference in color reproduction degree is 19,which is better than the industry standard value of 25.The developed tongue diagnosis instrument will promote the objective,efficient and precise acquisition of tongue diagnosis in traditional Chinese medicine.

OBJECTIVE To explore the effect of Astragali Radix-Curcuma Zedoaria-Paridis Rhizoma(Qi-Zhu-Zao)combina-tion on inhibiting the growth and metastasis of colon cancer based on the PINK1/Parkin/EMT signaling pathway.METHODS Thirty male BALB/c mice were randomly assigned to five groups:sham operation group,model group,positive control group,high-dose Qi-Zhu-Zao group(5.85 g·kg-1),and low-dose Qi-Zhu-Zao group(2.925 g·kg-1),with six mice in each group.An orthotopic colon cancer model was established in the mice using CT26.WT cells.After 15 days of treatment,tumor and liver tissues were collected from each group.Hematoxylin and eosin(HE)staining was performed to assess tumor metastasis,and transmission electron microscopy was used to observe mitochondrial autophagy in tumor tissues.The expression of mitochondrial autophagy-related proteins PINK1,Parkin,p62,and LC3-Ⅱ/LC3-Ⅰ was analyzed using Western blot and immunohistochemistry(IHC).Additionally,the expression levels of epithelial-mesenchymal transition(EMT)-related proteins and mRNA,including E-cadherin,N-cadherin,Vimentin,and Snail,were detected using Western blot,qPCR,and IHC staining.RESULTS Compared to the model group,mice in the treatment groups exhibited significantly reduced tumor volumes and fewer metastatic foci.Additionally,liver tissues showed pathological changes,and the overall growth condition of the mice was markedly improved;the tumor tissues in the treatment groups displayed selective mitochon-drial autophagy,accompanied by the formation of autophagosomes.The treatment influenced the PINK1/Parkin pathway-mediated mi-tochondrial autophagy biological process,with PINK1,Parkin,p62,and LC3-Ⅱ/LC3-Ⅰ levels being significantly upregulated(P<0.05,P<0.01),the high-dose group exhibited a more significant impact than the low-dose group(P<0.05,P<0.01).Furthermore,the treatment groups also showed significant reductions in the protein and mRNA levels of N-cadherin,Vimentin,and Snail(P<0.05,P<0.01),along with significant increases in the protein and mRNA levels of E-cadherin(P<0.05,P<0.01),these effects were more pronounced in the high-dose group compared to the low-dose group(P<0.05,P<0.01).CONCLUSION The herbal combination of Qi-Zhu-Zao inhibits tumor growth and metastasis to a certain extent in a mouse model of orthotopic transplantation of colon cancer.The underlying mechanism may involve the restoration of mitochondrial function through the PINK1/Parkin signaling pathway and the inhibition of the epithelial-mesenchymal transition(EMT)process,thereby achieving a therapeutic effect on colon cancer.

OBJECTIVE To explore the effect of Astragali Radix-Curcuma Zedoaria-Paridis Rhizoma(Qi-Zhu-Zao)combina-tion on inhibiting the growth and metastasis of colon cancer based on the PINK1/Parkin/EMT signaling pathway.METHODS Thirty male BALB/c mice were randomly assigned to five groups:sham operation group,model group,positive control group,high-dose Qi-Zhu-Zao group(5.85 g·kg-1),and low-dose Qi-Zhu-Zao group(2.925 g·kg-1),with six mice in each group.An orthotopic colon cancer model was established in the mice using CT26.WT cells.After 15 days of treatment,tumor and liver tissues were collected from each group.Hematoxylin and eosin(HE)staining was performed to assess tumor metastasis,and transmission electron microscopy was used to observe mitochondrial autophagy in tumor tissues.The expression of mitochondrial autophagy-related proteins PINK1,Parkin,p62,and LC3-Ⅱ/LC3-Ⅰ was analyzed using Western blot and immunohistochemistry(IHC).Additionally,the expression levels of epithelial-mesenchymal transition(EMT)-related proteins and mRNA,including E-cadherin,N-cadherin,Vimentin,and Snail,were detected using Western blot,qPCR,and IHC staining.RESULTS Compared to the model group,mice in the treatment groups exhibited significantly reduced tumor volumes and fewer metastatic foci.Additionally,liver tissues showed pathological changes,and the overall growth condition of the mice was markedly improved;the tumor tissues in the treatment groups displayed selective mitochon-drial autophagy,accompanied by the formation of autophagosomes.The treatment influenced the PINK1/Parkin pathway-mediated mi-tochondrial autophagy biological process,with PINK1,Parkin,p62,and LC3-Ⅱ/LC3-Ⅰ levels being significantly upregulated(P<0.05,P<0.01),the high-dose group exhibited a more significant impact than the low-dose group(P<0.05,P<0.01).Furthermore,the treatment groups also showed significant reductions in the protein and mRNA levels of N-cadherin,Vimentin,and Snail(P<0.05,P<0.01),along with significant increases in the protein and mRNA levels of E-cadherin(P<0.05,P<0.01),these effects were more pronounced in the high-dose group compared to the low-dose group(P<0.05,P<0.01).CONCLUSION The herbal combination of Qi-Zhu-Zao inhibits tumor growth and metastasis to a certain extent in a mouse model of orthotopic transplantation of colon cancer.The underlying mechanism may involve the restoration of mitochondrial function through the PINK1/Parkin signaling pathway and the inhibition of the epithelial-mesenchymal transition(EMT)process,thereby achieving a therapeutic effect on colon cancer.

Aiming at the problems of tongue diagnosis instruments relying on manual operation,uneven illumination,color distortion and lack of dynamic information,an automated operation black box tongue diagnosis instrument based on machine vision is proposed.This instrument utilizes machine vision technology and image processing algorithms to achieve automatic positioning and automatic acquisition of tongue manifestations.High-resolution camera technology enables the acquisition of 3-second dynamic videos and high-quality static images.The performance test results show that,based on the dual-camera geometric projection calibration algorithm,the average time for tongue recognition is less than 0.15 seconds.The diffuse reflection light source improves the gray uniformity to 76.74%,and the maximum color difference in color reproduction degree is 19,which is better than the industry standard value of 25.The developed tongue diagnosis instrument will promote the objective,efficient and precise acquisition of tongue diagnosis in traditional Chinese medicine.

OBJECTIVE: Early bolting of Saposhnikovia divaricata has seriously hindered its medicinal value and sustainable development of resources. The molecular mechanism of bolting and flowering of S. divaricata is still unclear and worth of research. In our study, we explored the transcriptome of the genes related to the bolting and flowering of S. divaricata. METHODS: The transcriptome library was constructed, sequenced, assembled and annotated from the bolting and unbolting leaves of S. divaricata by high-throughput sequencing at the bud and flowering stage. Focus on the pathways related to bolting and flowering in plants, and exploring genes. The expression of seven candidate genes was verified by real-time fluorescence quantitative PCR (qRT-PCR). RESULTS: Transcriptome results showed that 249 889 422 high-quality clean reads were obtained. A total of 67 866 unigenes were assembled with an average length of 948.1 bp. Trinity de Novo assembly produced 67 866 unigenes with an average length of 948.1 bp. Among 993 differentially expressed genes, 484 genes were significantly up-regulated and 509 genes were down-regulated in the SdM group. A total of 79 GO terms were significantly enriched for differentially expressed genes. KEGG results showed that 11 154 unigenes were enriched in 89 pathways. And 21 candidate genes related to bolting and flowering of S. divaricata were excavated. The qRT-PCR results showed that expression trends of HDA9, PHYB, AP2, TIR1, Hsp90, CaM, and IAA7 were consistent with transcriptomic sequencing results. In addition, RNA-seq had identified 10 740 transcription factors and classified them into 58 families by their conserved domains. Further studies showed that the transcription factors regulating the flowering of S. divaricata were mainly distributed in the NAC, MYB_related, HB-other, ARF, and AP2 families. CONCLUSION Based on the results of this study, it was found that the plant hormone signal transduction pathway was one of the decisive factors to control bolting and flowering. Among them, auxin related genes IAA and TIR1 are the key genes in the bolting and flowering process of S. divaricata.

Objective:To compare the pharmacokinetics and safety of single intravenous injection of the generic bevacizumab injection WBP264 and the original bevacizumab injection Avastin ? in healthy male volunteers. Methods:The study was designed as a randomized, double-blind, single dose, parallel, and controlled phase I clinical trial. Healthy male volunteers who were recruited publicly were randomized into the trial group (intravenous infusion of WBP264) and the control group (intravenous infusion of Avastin ?), and the dose was 3 mg/kg. Peripheral venous blood was collected within 30 minutes before administration, 45 minutes after onset of the administration, immediately after finishing the administration, 2.5, 3.5, 5.5, 9.5, 13.5, 24, 48 hours and on the 5th, 8th, 15th, 22nd, 29th, 36th, 43rd, 57th, 71st, 85th, and 99th days after the administration. The plasma concentration was measured by enzyme-linked immunosorbent assay, the plasma concentration-time curve and its semilogarithmic plot were plotted, and the pharmacokinetic parameters such as the area under the plasma concentration-time curve [including AUC from time zero to the time of the last quantifiable concentration (AUC 0-t) and AUC from time zero to infinity (AUC 0-∞)], peak concentration ( Cmax), time to peak ( Tmax), plasma elimination half-life ( t1/2), clearance rate (CL), and apparent volume of distribution (Vd) were calculated. When the 90% confidence intervals ( CI) of the geometric mean ratio of AUC 0-t, AUC 0-∞, and Cmax between the trial group and the control group were between 0.80-1.25, it indicated that pharmacokinetics of WBP264 and Avastin ? were similar. The physical examination, vital signs detection, electrocardiogram, and laboratory tests were performed on the subjects, the occurrence of adverse events (AEs) and the severity classification were recorded, and correlation between the AEs and the trial drug was evaluated. The anti-drug antibody and its neutralizing antibody were detected before administration and on the 8th, 15th, 29th, 43rd, 71st, and 99th days after administration to evaluate the immunogenicity of the drug. Results:A total of 78 subjects were recruited, 39 in the trial group and 39 in the control group. In the trial group, 2 cases withdrew from the trial (1 case did not take the drug and 1 case withdrew for personal reason after taking the drug). Seventy-seven cases were in the safety analysis set and 76 cases in the pharmacokinetic analysis set. The differences in age, height, weight, and body mass index between the 2 groups were not significant (all P>0.05). The plasma concentration-time curves of bevacizumab between the trial group and the control group were similar. The geometric mean ratios (90% CI) of AUC 0-t, AUC 0-∞, and Cmax were 1.04 (0.98-1.10), 1.03 (0.98-1.10), and 1.09 (1.03-1.14), respectively. The differences in the incidence of overall AEs [89.5% (34/38) vs. 87.2% (34/39)] and the incidence of AEs possibly related to the trial drug [86.8% (33/38) vs. 79.5% (31/39)] between the trial group and the control group were not significant (all P>0.05). Only one case of AE in the trial group was grade 3 in severity and was assessed as being not related to the drug, and the rest were grade 1-2, with grade 1 AEs accounting for the vast majority. The difference in the positive rate of anti-drug antibody between the trial group and the control group was not significant [10.5% (4/38) vs. 10.3% (4/39), P>0.05]. The neutralizing antibody test was negative in the patients with positive anti-drug antibody. Conclusion:The pharmacokinetics and safety of WBP264 and Avastin ? are similar.

Objective: To explore the commonalities and differences between primary school students and teachers in beliefs of myopia prevention and control, in order to provide a theoretical basis for the education programs of myopia prevention and control. Methods: Convenient sampling method was used to select 14 students and 16 teachers from grades 3 and 4 in two elementary schools in Hangzhou for one to one in depth interviews, and the results were coded and analyzed by using Nvivo 11.0 software. Results: There were commonalities in the perceived severity, benefits and barriers of myopia prevention and control beliefs among students and teachers, and the common keywords had been mentioned for 114 times, the commonalities of perceived severity, benefits and barriers were more obvious among them; there were differences in the specific attributions of perceived susceptibility, severity and barriers among students and teachers，the difference keywords had been mentioned for 63 times, the differences of perceived susceptibility, severity and barriers were more obvious among them. Conclusion There were commonalities in the perceived susceptibility, severity, benefits and barriers of myopia prevention and control beliefs between students and teachers; there were differences in the aspects of perceived susceptibility, severity and barriers between students and teachers. Adverse health outcomes of myopia and associated prevention knowledge should be enhanced among students. schools should carry out health education activities to improve the ability of teachers and students to prevent and control myopia; the government should implement the "double reduction" policy and improve the safety insurance system for outdoor activities.

Objective:To compare the pharmacokinetics and safety of single intravenous injection of the generic bevacizumab injection WBP264 and the original bevacizumab injection Avastin ? in healthy male volunteers. Methods:The study was designed as a randomized, double-blind, single dose, parallel, and controlled phase I clinical trial. Healthy male volunteers who were recruited publicly were randomized into the trial group (intravenous infusion of WBP264) and the control group (intravenous infusion of Avastin ?), and the dose was 3 mg/kg. Peripheral venous blood was collected within 30 minutes before administration, 45 minutes after onset of the administration, immediately after finishing the administration, 2.5, 3.5, 5.5, 9.5, 13.5, 24, 48 hours and on the 5th, 8th, 15th, 22nd, 29th, 36th, 43rd, 57th, 71st, 85th, and 99th days after the administration. The plasma concentration was measured by enzyme-linked immunosorbent assay, the plasma concentration-time curve and its semilogarithmic plot were plotted, and the pharmacokinetic parameters such as the area under the plasma concentration-time curve [including AUC from time zero to the time of the last quantifiable concentration (AUC 0-t) and AUC from time zero to infinity (AUC 0-∞)], peak concentration ( Cmax), time to peak ( Tmax), plasma elimination half-life ( t1/2), clearance rate (CL), and apparent volume of distribution (Vd) were calculated. When the 90% confidence intervals ( CI) of the geometric mean ratio of AUC 0-t, AUC 0-∞, and Cmax between the trial group and the control group were between 0.80-1.25, it indicated that pharmacokinetics of WBP264 and Avastin ? were similar. The physical examination, vital signs detection, electrocardiogram, and laboratory tests were performed on the subjects, the occurrence of adverse events (AEs) and the severity classification were recorded, and correlation between the AEs and the trial drug was evaluated. The anti-drug antibody and its neutralizing antibody were detected before administration and on the 8th, 15th, 29th, 43rd, 71st, and 99th days after administration to evaluate the immunogenicity of the drug. Results:A total of 78 subjects were recruited, 39 in the trial group and 39 in the control group. In the trial group, 2 cases withdrew from the trial (1 case did not take the drug and 1 case withdrew for personal reason after taking the drug). Seventy-seven cases were in the safety analysis set and 76 cases in the pharmacokinetic analysis set. The differences in age, height, weight, and body mass index between the 2 groups were not significant (all P>0.05). The plasma concentration-time curves of bevacizumab between the trial group and the control group were similar. The geometric mean ratios (90% CI) of AUC 0-t, AUC 0-∞, and Cmax were 1.04 (0.98-1.10), 1.03 (0.98-1.10), and 1.09 (1.03-1.14), respectively. The differences in the incidence of overall AEs [89.5% (34/38) vs. 87.2% (34/39)] and the incidence of AEs possibly related to the trial drug [86.8% (33/38) vs. 79.5% (31/39)] between the trial group and the control group were not significant (all P>0.05). Only one case of AE in the trial group was grade 3 in severity and was assessed as being not related to the drug, and the rest were grade 1-2, with grade 1 AEs accounting for the vast majority. The difference in the positive rate of anti-drug antibody between the trial group and the control group was not significant [10.5% (4/38) vs. 10.3% (4/39), P>0.05]. The neutralizing antibody test was negative in the patients with positive anti-drug antibody. Conclusion:The pharmacokinetics and safety of WBP264 and Avastin ? are similar.

As the main factor leading to foodborne illnesses, foodborne pathogens have been attached great importance by people. The development of simple, rapid, high-sensitivity and low-cost food-borne pathogen detection methods is of great significance in reducing the incidence of foodborne diseases. Biosensor technology is a new micro-analysis technology developed by multi-disciplinary cross-infiltration. It has the characteristics of high sensitivity and fast analysis speed, and is widely used in the detection of food-borne pathogens. This paper introduces the basic principles of biosensors, summarizes the application of common biosensors in the detection of foodborne pathogens, and prospects for future development.
Biosensing Techniques ; Food Microbiology ; Foodborne Diseases ; Humans