Objective To explore the efficacy of artificial tiger bone powder in the treatment of knee osteoarthritis(KOA)through Wnt/β-catenin pathway.Methods Forty SD rats were divided into control group,KOA group,low-dose group and high-dose group.The KOA group,low-dose group and high-dose group were all modeled by anterior cruciate ligament transection.After modeling,high-dose and low-dose groups were treated with artificial tiger bone powder at a dose of 10g/kg and 5g/kg orally respectively.Cartilage tissue specimens of rats in each group were collected for hematoxylin-eosin staining and immunohistochemical staining,and Mankin score was conducted.The cartilage tissues of the knee joints of normal SD rats were taken for primary chondrocyte culture.After passage,they were divided into blank group(without any stimulation),interleukin-1β(IL-1β)group(incubated with 10ng/ml IL-1β for 1 day),and IL-1β+artificial tiger bone powder group(incubated with 10ng/ml IL-1β and 10μg/ml artificial tiger bone powder for 1 day).Detect the activities of related substances such as typeⅡ collagen(Col Ⅱ),matrix metalloproteinase-13(MMP-13),and β-catenin in each group.Results Compared with KOA group,after artificial tiger bone powder treatment,the degree of redness and swelling of the knee joints in rats was reduced,the range of joint motion was significantly improved,and the levels of inflammatory factors were decreased.Compared with the IL-1β group,the expression levels of Col Ⅱ protein and mRNA in IL-1β+artificial tiger bone powder group were significantly increased(P＜0.05),while the expression levels of MMP-13,β-catenin protein and mRNA decreased significantly(P＜0.05).After adding the Wnt agonist LiCL,the mRNA expression levels of Wnt1,β-catenin and MMP-13 increased,while the addition of the Wnt inhibitor WIF1 could reduce the mRNA expression levels of Wnt1,β-catenin and MMP-13.Conclusion Artificial tiger bone powder can inhibit the progression of KOA by regulating Wnt/β-catenin pathway.

Objective To investigate the correlation between the peripheral blood levels of long non-coding RNA urothelial carcinoma associated 1(lncRNA UCA1)and miR-665 with the occur-rence of coronary restenosis in patients with ACS after interventional treatment.Methods A total of 315 ACS patients admitted to the Affiliated Hospital of Hebei University from July 2022 to Ju-ly 2023 were recruited and then divided into occurrence group(62 cases)and non-occurrence group(253 cases)according to the occurrence of coronary restenosis.The expression of lncRNA UCA1 and miR-665 in peripheral blood samples was detected by real-time fluorescence quantita-tive PCR.Pearson analysis was applied to analyze the correlation between peripheral blood ln-cRNA UCA1 and miR-665 in ACS patients.Logistic regression analysis was used to identify the influencing factors for coronary restenosis in ACS patients.ROC curve was plotted to analyze the predictive value of peripheral blood lncRNA UCA1 and miR-665 for the restenosis,and their AUC values were calculated.Results The peripheral blood expression of lncRNA UCA1 was signifi-cantly higher,and that of miR-665 was obviously lower in the occurrence group than the non-occurrence group(1.28±0.22 vs 1.01±0.21,P=0.001;0.76±0.24 vs 1.01±0.22,P=0.001).Pearson analysis showed there was a negative correlation between miR-665 and lncRNA UCA1 expression levels in the ACS patients(r=-0.585,P＜0.05).Multivariate logistic regression anal-ysis indicated that LncRNA UCA1 was a risk factor(OR=2.124,95％CI:1.324-3.406,P=0.002),and miR-665 was a protective factor(OR=0.765,95％CI:0.653-0.897,P=0.001)for the occurrence of coronary restenosis in ACS patients after interventional treatment.ROC curve analysis revealed that the combination of peripheral blood lncRNA UCA1 and miR-665 had the highest AUC value in predicting the occurrence of coronary restenosis,which was better than the value of single molecule(Z=2.256,P=0.024;Z=2.904,P=0.004).Conclusion Combination of peripheral blood levels of lncRNA UCA1 and miR-665 has good performance for predicting coro-nary restenosis in ACS patients after interventional therapy.

Objective To explore the efficacy of artificial tiger bone powder in the treatment of knee osteoarthritis(KOA)through Wnt/β-catenin pathway.Methods Forty SD rats were divided into control group,KOA group,low-dose group and high-dose group.The KOA group,low-dose group and high-dose group were all modeled by anterior cruciate ligament transection.After modeling,high-dose and low-dose groups were treated with artificial tiger bone powder at a dose of 10g/kg and 5g/kg orally respectively.Cartilage tissue specimens of rats in each group were collected for hematoxylin-eosin staining and immunohistochemical staining,and Mankin score was conducted.The cartilage tissues of the knee joints of normal SD rats were taken for primary chondrocyte culture.After passage,they were divided into blank group(without any stimulation),interleukin-1β(IL-1β)group(incubated with 10ng/ml IL-1β for 1 day),and IL-1β+artificial tiger bone powder group(incubated with 10ng/ml IL-1β and 10μg/ml artificial tiger bone powder for 1 day).Detect the activities of related substances such as typeⅡ collagen(Col Ⅱ),matrix metalloproteinase-13(MMP-13),and β-catenin in each group.Results Compared with KOA group,after artificial tiger bone powder treatment,the degree of redness and swelling of the knee joints in rats was reduced,the range of joint motion was significantly improved,and the levels of inflammatory factors were decreased.Compared with the IL-1β group,the expression levels of Col Ⅱ protein and mRNA in IL-1β+artificial tiger bone powder group were significantly increased(P＜0.05),while the expression levels of MMP-13,β-catenin protein and mRNA decreased significantly(P＜0.05).After adding the Wnt agonist LiCL,the mRNA expression levels of Wnt1,β-catenin and MMP-13 increased,while the addition of the Wnt inhibitor WIF1 could reduce the mRNA expression levels of Wnt1,β-catenin and MMP-13.Conclusion Artificial tiger bone powder can inhibit the progression of KOA by regulating Wnt/β-catenin pathway.

OBJECTIVE:Researches show that a combination of platelet-rich plasma and adipose-derived stem cells can accelerate the healing of skin lesions.However,systematic evidence for the combination of the two is still lacking.The purpose of this study was to assess the efficacy of a combination of two interventions in a clinical rodent skin wound model.METHODS:We searched PubMed,Embase,Cochrane,and CNKI and selected the studies of platelet-rich plasma,adipose-derived stem cell transplantation,or their combination on skin wounds in experimental animals published until July 2023.Wound healing and wound transformation growth factor β,CD31,type Ⅰ collagen,and vascular endothelial growth factor were used as indicators.RevMan 5.3 and Stata 15.0 were used to analyze the data.RESULTS:A total of 12 studies were included,of which 8 studies used rats as experimental subjects and 4 studies used mice as experimental subjects.The experimental group was treated with platelet-rich plasma combined with adipose-stem cell transplantation,and the control group was treated with platelet-rich plasma alone.The results of meta-analysis showed that the wound healing rate of the experimental group at 3,7,and 10 days after treatment was greater than that of the control group[SMD=2.65,95％CI(1.29,4.01),Z=3.81,P=0.0001;SMD=3.38,95％CI(2.47,4.30),Z=7.24,P<0.00001;SMD=2.62,95％CI(1.50,3.73),Z=4.61,P<0.00001].The wound healing time of the experimental group was shorter than that of the control group[SMD=-2.12,95％CI(-3.5,-0.74),P=0.003].The expression of transforming growth factor β,positive rate of CD31,expression of type Ⅰ collagen,and vascular endothelial growth factor in wound of experimental group were higher than those of control group[SMD=5.65,95％CI(1.22,10.08),Z=2.50,P=0.01;SMD=2.49,95％CI(1.96,3.02),Z=9.28,P<0.00001;SMD=3.44,95％CI(0.72,6.17),Z=2.48,P=0.01;SMD=2.38,95％CI(0.97,3.79),Z=3.30,P=0.0010].CONCLUSION:Our results show that platelet-rich plasma+adipose-derived stem cells combined treatment can improve the wound healing rate,shorten the wound healing time,and at the same time increase the expression of transforming growth factor β,CD31,type Ⅰ collagen,and vascular endothelial growth factor to accelerate healing.Due to the limitations of the model,more animal testing and clinical trials are needed.

Traumatic brain injury(TBI)is mostly caused by motor vehicle traffic accidents or competitive sports,with high mortality and disability.TBI mainly includes primary injury and secondary injury.Primary injuries were caused directly by external forces.Secondary injuries include brain edema,excitotoxic effect of neuron cells,oxidative stress and neuroinflammation,etc.Effective intervention of secondary injury not only helps to improve the prognosis of patients with TBI,but also reduces the risk of Parkinson's disease and other neurodegenerative diseases related to TBI.Autophagy is one of approaches to regulate homeostasis in cells,and autophagy dysfunction has been found in several neurodegenerative diseases and TBI.It is speculated that autophagy dysfunction may play an important role in TBI and explain why patients with TBI have higher risk of neurodegenerative disease.Discovering the role of autophagy in the pathological mechanism of TBI may provide new targets for TBI clinical treatment and cognitive impairment prevention in patients with TBI.

Objective:To explore the influence of LIN28B on chemosensitivity of colon cancer by regulating GSH.Methods:Functional enrichment analysis of LIN28B target genes was performed using database. The primary tumor tissues of colon cancer patients who received neoadjuvant chemotherapy at Department of Gastroenterology, Peking University International Hospital from Nov 2017 to May 2020 were collected, and their LIN28B levels were detected by immunohistochemistry. According to the tumor regression grade, they were divided into chemotherapy sensitive group and chemotherapy resistant group, and the difference of LIN28B expression between the two groups was compared. LIN28B overexpression and knockdown colon cancer cell lines were constructed, and the effect of LIN28B on the chemosensitivity of colon cancer cells was detected by MTT assay. Double luciferase reporting experiment and Western blot were used to detect the direct binding and regulation of LIN28B to mRNA of four GSH related enzymes. At the same time, the regulation of LIN28B on total GSH and reduced GSH was tested. Finally, by detecting the level of reactive oxygen species (ROS) γ-H2AX and Comet assay to analyze the potential impact of LIN28B on genomic instability.Results:GSH-related enzymes were highly enriched in LIN28B target genes. The expression of LIN28B was heterogeneous in colon cancer patients. Compared with the low expression group, the average survival time of patients with high expression of LIN28B was significantly increased [(50.2±2.9 )months vs. (31.1±4.0 )months, P=0.001], and the proportion of tumor regression grade 0-1 was significantly different (48.0% vs. 16.0%, P=0.032). The expression level of LIN28B in chemotherapy sensitive group was significantly higher than that in drug resistant group ( P<0.01). LIN28B overexpression significantly increased the chemosensitivity of HCT116 cells to 5-fluorouracil (5-Fu) and oxaliplatin (L-OPH). The synthesis and activity of GSH were further inhibited (all P<0.01). At the same time, the ROS level of LIN28B overexpression cells was significantly increased after treatment with L-OPH. The level of γ-H2AX was significantly increased, and the content of comet tail DNA was also significantly increased ( P<0.01). Conclusion:LIN28B may increase the chemosensitivity of colon cancer cells by directly inhibiting the expression of GSH related enzymes, resulting in the decrease of GSH synthesis and activity, the increase of ROS level and genomic instability.

OBJECTIVE:Researches show that a combination of platelet-rich plasma and adipose-derived stem cells can accelerate the healing of skin lesions.However,systematic evidence for the combination of the two is still lacking.The purpose of this study was to assess the efficacy of a combination of two interventions in a clinical rodent skin wound model.METHODS:We searched PubMed,Embase,Cochrane,and CNKI and selected the studies of platelet-rich plasma,adipose-derived stem cell transplantation,or their combination on skin wounds in experimental animals published until July 2023.Wound healing and wound transformation growth factor β,CD31,type Ⅰ collagen,and vascular endothelial growth factor were used as indicators.RevMan 5.3 and Stata 15.0 were used to analyze the data.RESULTS:A total of 12 studies were included,of which 8 studies used rats as experimental subjects and 4 studies used mice as experimental subjects.The experimental group was treated with platelet-rich plasma combined with adipose-stem cell transplantation,and the control group was treated with platelet-rich plasma alone.The results of meta-analysis showed that the wound healing rate of the experimental group at 3,7,and 10 days after treatment was greater than that of the control group[SMD=2.65,95％CI(1.29,4.01),Z=3.81,P=0.0001;SMD=3.38,95％CI(2.47,4.30),Z=7.24,P<0.00001;SMD=2.62,95％CI(1.50,3.73),Z=4.61,P<0.00001].The wound healing time of the experimental group was shorter than that of the control group[SMD=-2.12,95％CI(-3.5,-0.74),P=0.003].The expression of transforming growth factor β,positive rate of CD31,expression of type Ⅰ collagen,and vascular endothelial growth factor in wound of experimental group were higher than those of control group[SMD=5.65,95％CI(1.22,10.08),Z=2.50,P=0.01;SMD=2.49,95％CI(1.96,3.02),Z=9.28,P<0.00001;SMD=3.44,95％CI(0.72,6.17),Z=2.48,P=0.01;SMD=2.38,95％CI(0.97,3.79),Z=3.30,P=0.0010].CONCLUSION:Our results show that platelet-rich plasma+adipose-derived stem cells combined treatment can improve the wound healing rate,shorten the wound healing time,and at the same time increase the expression of transforming growth factor β,CD31,type Ⅰ collagen,and vascular endothelial growth factor to accelerate healing.Due to the limitations of the model,more animal testing and clinical trials are needed.

Objective:To investigate the efficacy of oral folic acid intervention in lung cancer patients with radiation esophagitis (RE) caused by concurrent chemoradiotherapy.Methods:In this randomized, controlled, single-center clinical trial, a total of 82 patients with stage N 2-N 3 lung cancer including small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC) admitted to the Affiliated Cancer Hospital of Guizhou Medical University from June 2022 to October 2023 were prospectively included. All enrolled patients were randomly divided into the experimental group (folic acid group) and control group according to 1 vs. 1 of simple random method, and patients in both groups were required to receive radiation therapy for lung lesions and mediastinal metastatic lymph nodes [≥2 cycles of chemotherapy were completed during the same period of radiotherapy (≥40 Gy / 20 F) or targeted drugs were given simultaneously]. The severity of RE was evaluated using the modified common terminology criteria for adverse events criteria of the National Cancer Institute in both groups weekly at the onset of radiation esophagitis symptoms and thereafter until 1 week after the end of radiotherapy. Conventional treatment of RE was delivered according to the grading criteria of the Radiation Therapy Oncology Group. Patients in the folic acid group were given with folic acid tablets 30 mg/d orally at the beginning of radiotherapy until the end of radiotherapy, while those in the control group did not receive any drug intervention. The onset time, severity and duration of RE, and changes in the severity of esophageal toxicity after conventional treatment were recorded and analyzed. Serum folate value, serum vitamin B 12 value and homocysteine value were measured before and after radiotherapy. For continuous quantitative variables, independent sample t-test or independent sample rank-sum test was used for comparison among different groups. For categorical data, Chi-square test or Fisher's exact probability method was used for comparison among different groups. Results:During the observation period, no grade 4 or above RE was reported between two groups. The incidence of grade 0, 1, 2 and 3 RE in the folic acid and control groups was 10% (4/40) and 5% (2/41), 70% (28/40) and 42% (17/41), 15% (6/40) and 51% (21/41), 5% (2/40) and 2% (1/41), respectively. The differences were not statistically significant between two groups ( P=0.456). However, the incidence of grade 0-1 RE in the folic acid group was significantly higher than that in the control group ( Z=2.72, P=0.006). The median time of RE in the folic acid group and control group was 12 d (range 7-52 d) and 15 d (range 11-56 d) after the start of radiotherapy, respectively, with no statistically significant difference ( χ2=-0.75, P=0.456). However, median duration of the individual's most severe RE was 12 d (range 4-36 d) and 21 d (range 7-38 d) in the folic acid group and control groups, respectively, and the differences were statistically significant ( χ2=2.10, P=0.039). In the folic acid group, the grades of swallowing with pain and dysphagia were significantly declined after folic acid intervention, especially at 2 weeks after the occurrence of RE ( P=0.001, P=0.002). The remission rate of RE after 1 week in the folic acid group was higher than that in the control group, and the difference was statistically significant ( χ2=7.36, P=0.012). Conclusion:Oral intake of folic acid during concurrent chemoradiotherapy for lung cancer cannot reduce the incidence of RE, but it may reduce its severity, shorten the duration of the most severe RE in individuals, and have a certain protective effect.

Objective To provide technical support for the formulation of scientific and reasonable supervision measures for enterprises engaged in the exploitation and utilization of ores with associated radionuclides in Guangxi Province, China. Methods A radionuclide analysis was performed on solid materials generated during production processes such as zirconium-titanium ore dressing and processing in multiple enterprises in Guangxi Province. The radiation levels of effluents was measured. Measurement and analysis were performed on the environmental air radon concentration levels and environmental γ-radiation dose rates at the factory boundaries of these enterprises and the surrounding environmental protection targets. Results The air absorption dose rate of γ radiation, the concentrations of radon and its daughters, and the radiation levels of surface water and aerosols at the factory boundaries and in the surrounding environment were all at normal levels. The specific activities of nuclides ²³⁸U, ²³²Th, and ²²⁶Ra in the raw ore, zirconium products, rutile products, and monazite products within the factory area were relatively high. The γ radiation air absorption dose rates in the corresponding workshops were also relatively high, with the zirconium-rutile workshop being the area with the highest values. Materials such as zirconium products, rutile, and monazite all showed a certain amount of radon exhalation. Conclusion The radiation level of tailings met the criteria of monitoring exemption, and the enterprises did not generate radioactive solid waste. Attention should be paid to the personal dose of the staff in areas with high radiation dose rates.

Objective:To investigate the impact of limonin(LIM)on the necrotic apoptosis of myocardial cells in rats with myocardial infarction(MI)by regulating the receptor-interacting protein 1(RIP1)/receptor-interacting protein 3(RIP3)/mixed-lineage kinase domain-like protein(MLKL)signaling pathway.Methods:A total of 60 Sprague-Dawley rats were randomly divided into sham-operation group(Sham group),MI model group(Model group),low-dose LIM group(LIM-L group,25 mg/kg LIM),high-dose LIM group(LIM-H group,50 mg/kg LIM),and high-dose LIM+RIP1 inhibitor Nec-1 group(LIM-H+Nec-1 group,50 mg/kg LIM+0.6 mg/kg Nec-1),with 12 rats in each group.A rat model of MI was established by ligation of the coronary artery.The changes of cardiac func-tion were examined for each group;HE staining was used to observe the pathological changes of myocardial tissue;the 2,3,5-triphen-yltetrazolium chloride-Evans blue method was used to measure myocardial infarct area;the terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling method was used to observe the necrotic apoptosis of myocardial cells;quantitative real-time PCR and Western blot were used to measure the expression levels of mRNAs and proteins associated with the RIP1/RIP3/MLKL signaling pathway and the expression of apoptosis-related proteins.Results:Compared with the Sham group,the Model group had significant re-ductions in left ventricular ejection fraction,left ventricular systolic pressure,and the expression level of B-cell lymphoma-2(Bcl-2)in myocardial tissue(all P<0.001)and significant increases in left ventricular end-systolic volume,left ventricular end-diastolic pres-sure,left ventricular end-diastolic volume,myocardial infarct area,cell apoptosis rate,the mRNA and protein expression levels of RIP1,RIP3,and MLKL in myocardial tissue,and the protein expression levels of Bcl-2 associated X protein and cysteinyl aspartate-specific proteinase 3 in myocardial tissue(all P<0.001),as well as swelling and disordered arrangement of myocardial cells with ne-crosis and massive inflammatory cell infiltration on HE pathological sections.Compared with the Model group,the LIM-H group showed reverse changes in the above indicators(RIP1 mRNA:P=0.002,RIP3 mRNA:P=0.008,and the other indexes P were all<0.001),with alleviations of myocardial histopathological injury and inflammatory cell infiltration.Nec-1 promoted the effect of LIM in alleviating the necrotic apoptosis of myocardial cells in MI rats.Conclusion:LIM may alleviate the necrotic apoptosis of myocardial cells in MI rats by downregulating the RIP1/RIP3/MLKL signaling pathway.