BACKGROUND:As a common disease in middle-aged and elderly,osteoarthritis is difficult to cure,and the pathogenesis is not clear.Long non-coding RNA participates in the pathogenesis of osteoarthritis through many ways,such as regulating translation,promoting or inhibiting mRNA,and adsorbing miRNAs. OBJECTIVE:To review the types of common long non-coding RNA in osteoarthritis,and the influence of multiple long non-coding RNAs on the pathological factors related to osteoarthritis,to analyze the future application of long non-coding RNAs in osteoarthritis. METHODS:Literature retrieval was conducted in CNKI,WanFang Data,VIP database,PubMed,Web of Science and Sciencedirect databases,using the search terms of"osteoarthritis,degenerative joint disease,degenerative arthritis,OA,LncRNA,long non-coding RNA,long noncoding RNA,long intergenic non-coding RNA"in Chinese and English.All relevant literature published from 1976 and May 2024 was retrieved.After literature screening,induction,analysis and summary,93 articles were finally included for review. RESULTS AND CONCLUSION:This review collected 25 long non-coding RNAs that are well studied with osteoarthritis.Long non-coding RNAs,as a molecular sponge for miRNA,are competing endogenous RNAs to competitively adsorb miRNAs and then affect downstream targets.Long non-coding RNAs can regulate physiopathological processes such as chondrocyte apoptosis and proliferation,cartilage extracellular matrix degradation,and inflammatory responses.Long non-coding RNAs are expected to become a biomarker and potential therapeutic target for the clinical diagnosis and therapeutic prognosis of osteoarthritis,and it may become a new strategy for the clinical treatment of osteoarthritis in the future.

Objective : To observe the brain tissue injury during hypoxia-ischemia, as well as the pathological changes and the expression of ferroptosis-related factors after the use of Shenfu injection(SFI), and to explore the protective effect of SFI on hypoxic-ischemic brain injury(HIBD) by inhibiting ferroptosis. Methods : An animal model of HIBD in SD rats was constructed and intervened with SFI. Pathologic changes in brain tissue were observed by HE staining methods. Nissen staining was used to observe neuron survival. Glutathione Peroxidase 4(GPX4) and Divalent Metal Transporter 1(DMT1) expression were detected in brain tissue by Western blot, immunohistochemistry and immunofluorescence. Reduced Glutathione(GSH), Lactate Dehydrogenase(LDH), Malondialdehyde(MDA), Superoxide Dismutase(SOD) and tissue iron content were determined with the kits. BV-2 microglial cell line(BV2) cells were culturedin vitroand divided into control group(Ctrl group), oxygen-glucose deprivation group(OGD group), iron ferroptosis-inducing group(Erastin group), iron ferroptosis-inhibiting group(Fer-1 group), Shenfu injection group(SFI group), and Erastin+Shenfu injection group(Erastin+SFI group). 2′,7′-Dichlorodihydrofluorescein diacetate(DCFH-DA) reactive oxygen species(ROS) fluorescent probe was used to detect the ROS release level; Immunofluorescence was used to observe intracellular GPX4, DMT1 expression. Results : Compared with the Sham group, rats in the HIBD group showed significant neuronal cell damage in brain tissue, decreased GPX4 expression(P<0.01), increased DMT1 expression(P<0.01), decreased GSH and SOD levels(P<0.01), and increased LDH, MDA and tissue iron levels(P<0.05,P<0.05,P<0.01). In contrast, after the intervention of SFI, GPX4 expression was elevated(P<0.01), DMT1 expression decreased(P<0.01), GSH and SOD levels were elevated(P<0.01), and LDH, MDA, and tissue iron levels decreased(P<0.05,P<0.05,P<0.01). The cells experiments showed that compared with the Ctrl group, the OGD group had a significantly higher ROS content and a decrease in the expression of GPX4 fluorescence intensity, and an increase in the fluorescence intensity of DMT1(P<0.01), compared with the OGD group, the ROS content was reduced in the SFI group, while the expression of GPX4 was elevated and the expression of DMT1 was reduced(P<0.01). Conclusion Hippocampal and cortical regions are severely damaged after HIBD in neonatal rats, and their brain tissues show decreased expression of GPX4 and increased expression of DMT1. The above suggests that ferroptosis is involved in HIBD brain injury in neonatal rats. In contrast, Shenfu injection has a protective effect on HIBD experimental animal model and BV2 cell injury model by reducing iron aggregation and ROS production.

BACKGROUND: The association of systemic inflammatory response index (SIRI) with prognosis of coronary artery disease (CAD) patients has never been investigated in a large sample with long-term follow-up. This study aimed to explore the association of SIRI with all-cause and cause-specific mortality in a nationally representative sample of CAD patients from United States. METHODS: A total of 3386 participants with CAD from the National Health and Nutrition Examination Survey (NHANES) 1999-2018 were included in this study. Cox proportional hazards model, restricted cubic spline (RCS), and receiver operating characteristic curve (ROC) were performed to investigate the association of SIRI with all-cause and cause-specific mortality. Piece-wise linear regression and sensitivity analyses were also performed. RESULTS: During a median follow-up of 7.7 years, 1454 all-cause mortality occurred. After adjusting for confounding factors, higher lnSIRI was significantly associated with higher risk of all-cause (HR = 1.16, 95% CI: 1.09-1.23) and CVD mortality (HR = 1.17, 95% CI: 1.05-1.30) but not cancer mortality (HR = 1.17, 95% CI: 0.99-1.38). The associations of SIRI with all-cause and CVD mortality were detected as J-shaped with threshold values of 1.05935 and 1.122946 for SIRI, respectively. ROC curves showed that lnSIRI had robust predictive effect both in short and long terms. CONCLUSIONS SIRI was independently associated with all-cause and CVD mortality, and the dose-response relationship was J-shaped. SIRI might serve as a valid predictor for all-cause and CVD mortality both in the short and long terms.

ObjectiveTo investigate the syndrome evolution patterns， characteristics of the used herbal medicinals， and efficacy variations across different stages of rheumatoid arthritis （RA） progression. MethodsBased on the China Rheumatoid Arthritis Registry of Patients with Chinese Medicine （CERTAIN）， 2,506 RA patients were retrospectively enrolled and categorized into ＜6 months group （166 cases）， 6 months to ＜5 years group （1063 cases）， 5 to ＜20 years group （1067 cases）， and ≥20 years group （210 cases）. Syndromes were differentiated before and after traditional Chinese medicine （TCM） treatment， including damp-heat obstruction， wind-damp obstruction， cold-damp obstruction， blood stasis obstructed in the collaterals， phlegm-stasis obstruction， liver-kidney insufficiency， qi and blood deficiency， and qi-yin deficiency. The syndrome evolution rate was calculated for high-frequency syndromes before and after treatment. Analysis was conducted on top 20 frequently used Chinese herbs at the first diagnosis. Clinical efficacy of the 28-joint disease activity score based on erythrocyte sedimentation rate （DAS28-ESR） and 28-joint disease activity score based on C-reactive protein （DAS28-CRP） before and after treatment were assessed. A multivariate logistic regression analysis was performed to identify factors affecting the efficacy of TCM treatment. ResultsPatients with course of disease shorter than 6 months predominantly presented with cold-dampness obstruction syndrome （49/166， 29.5%）， wind-dampness obstruction syndrome （46/166， 27.7%）， and dampness-heat obstruction syndrome （43/166， 25.9%）. For patients with course of disease logner than 6 months and shorter than 5 years and those within 5 to 20 years， the dominant syndrome was dampness-heat obstruction syndrome （324/1063， 30.5% and 318/1067， 29.8%， respectively）. In patients with disease duration ≥20 years， liver-kidney insufficiency syndrome and dampness-heat obstruction syndrome both predominated， each accounting for 25.24% （53/210）. The syndromes with more than 100 cases before treatment and a syndrome evolution rate greater than 10% after treatment were dampness-heat obstruction （201/738， 27.2%）， liver-kidney insufficiency （119/367， 32.4%）， and phlegm-stasis obstruction syndromes （73/172， 42.4%）. These were classified as high-frequency syndromes. After treatment， damp-heat obstruction syndrome and liver-kidney insufficiency syndrome primarily evolved into wind-damp obstruction syndrome， while phlegm-stasis obstruction syndrome evolved into damp-heat obstruction and cold-damp obstruction syndrome. The top two commonly used Chinese herbs across all groups were Gancao （Radix et Rhizoma Glycyrrhizae） and Baishao （Radix Paeoniae Alba）. In the ＜6 months group and the 6 months to ＜5 years group， high-frequency herbs also included Fangfeng （Radix Saposhnikoviae）， Duhuo （Radix Angelicae Pubescentis）， Chuanxiong （Rhizoma Chuanxiong）， and Qianghuo （Radix et Rhizoma Notopterygii）. In the 5 to ＜20 years group and the ≥20 years group， the usage of Huangqi （Radix Astragali）， Fuling （Poria）， Niuxi （Radix Achyranthis Bidentatae）， and Danggui （Radix Angelicae Sinensis） increased， while the proportion of Fangfeng and Duhuo decreased. After treatment， the DAS28-ESR and DAS28-CRP scores in all groups significantly decreased （P＜0.05）. There were statistically significant differences in clinical efficacy based on DAS28-ESR and DAS28-CRP across all groups （P＜0.01）. Multivariate logistic regression revealed significantly reduced treatment efficacy in the 6 months-5 years group （OR=0.4）， 5~20 years group （OR=0.5）， and ≥20 years group （OR=0.4） compared to the ＜6 months group. ConclusionRA syndromes follow a progression pattern from excess to deficiency， with corresponding transition in herbal usage from pathogen-eliminating to healthy qi-reinforcing approaches. TCM intervention can significantly reduce disease activity of RA， with superior efficacy in patients with disease duration shorter than 6 months.

Objective:Survival analysis of cancers' incidence data in Tianjin from 2010 to 2016 was conducted to provide the basis for formulating and evaluating regional health policies on cancer prevention and treatment.Methods:Registration data in Tianjin were used between January 1, 2010 to December 31, 2016 and patients were followed-up till 31 December, 2021. Life-table method was used to calculate the observed survival rate and Edered Ⅱ was used to calculate the relative survival rate. The data were stratified by year, gender, age group and cancer sites. Difference in survival curves between group was analyzed by Kaplan-Meier method and Log rank test. Joinpoint regression model was used to analyze the trend change.Results:The 5-year relative survival rates of cancer were 41.92% to 53.65% from 2010 to 2016 for residents in Tianjin, with an increasing trend ( t=4.81 ,P=0.005), and the average was 48.56%. The survival rate of females was higher than that of males (57.71%vs. 39.20%), and the survival rate of urban residents was higher than that of rural residents (49.38% vs. 47.24%). The 5-year relative survival rates were 63.14%, 78.39%, 58.25% and 32.67% in 0-14, 15-44, 45-64 and 65 and above age groups, respectively. The median relative survival times of all cancer were 2.34 to 6.00 years from 2010 to 2016 in Tianjin, with an increasing trend ( t=3.86, P=0.012). The average of median relative survival times was 4.11 years. The median survival time of females was longer than that of males (11.99 years vs. 2.03 years), and the time of urban residents were longer than that of rural residents (4.60 years vs. 3.43 years). The median relative survival time were 12.07, 11.92 and 1.34 years in 15-44, 45-64 and 65 and above age groups, respectively. Conclusions:The cumulative survival rate of cancer increased significantly from 2010 to 2016 in Tianjin, indicating that the prevention and treatment effect of cancer is obvious. The focus should be on male, rural areas, higher age group, and targeted prevention and treatment measures should be taken to lung, esophagus, liver, gallbladder and pancreatic cancer.

Objective:To explore the trends and distribution of liver cancer between sexes, ages, and urban-rural areas in Tianjin, China from 1999 to 2021, and provide data for targeted prevention and control strategies of liver cancer in Tianjin.Methods:Liver cancer mortality data of Tianjin during 1999-2021 were from the Tianjin population based mortality surveillance system maintained by the Tianjin Centers for Disease Control and Prevention (CDC), and the population data of permanent Tianjin residents were from Tianjin Municipal Public Security Bureau. Liver cancer mortality, years of life lost (YLL), years lived with disability (YLD), and disability adjusted life years (DALY) were calculated using the cause of death surveillance data collected by Tianjin Centers for Disease Control and Prevention. The distributions of these data among residents of different sexes, ages, and regions were analyzed. Segi's world standard population was used for standardization. Joinpoint regression was used for trend analysis on the mortality rate of liver cancer and the disease burden.Results:The liver cancer mortality rate in Tianjin decreased by 46.75% from 1999 to 2021, with distinct phased characteristics. From 1999 to 2010, the age-sex-standardized mortality rate (SMR) decreased from 12.62/100 000 to 11.64/100 000 with an annual percent change (APC) of -1.32% ( P=0.003). From 2010 to 2021, the SMR decreased from 11.64/100 000 to 6.72/100 000 (APC=-3.89%, P＜0.001). The age-sex-standardized DALY rates(SDR) decreased by 50.63% from 1999 to 2021, also with distinct phased characteristics. From 1999 to 2010, the SDR decreased from 388.67/100 000 to 349.38/100 000 (APC=-1.35%, P=0.002). From 2010 to 2021, the SDR decreased from 349.38/100 000 to 191.88/100 000 (APC=-4.43%, P＜0.001). The liver cancer mortality rate declined most rapidly in the age group under 45 years; the APC for those under 35 years was -5.07% ( P＜0.001), and for those aged 35-44 years, the APC was 0.63% ( P=0.707) and -8.21% ( P＜0.001) before and after 2007, respectively. Both SMR and SDR were significantly higher in males than in females ( P＜0.01). Both SMR and SDR were significantly higher in urban areas than in rural areas from 1999 to 2007 ( P＜0.05), but they became similar after 2008. Liver cancer DALY are predominantly YLL, accounting for 99%. The median age of liver cancer deaths in Tianjin during 1999-2021 was 64-68 years old, with males lower than females ( P＜0.05), and rural areas lower than urban areas ( P＜0.05), generally showing an increasing trend (1999-2014: APC=0.11%, P=0.047; 2014-2021: APC=0.51%, P=0.005). Conclusions:Liver cancer mortality rate and disease burden decreased from 1999 to 2021 in Tianjin, with an especially accelerated decline after 2010. Further efforts to reduce liver cancer mortality in Tianjin are needed, and special attention should be focused on the elderly, male, and rural residents.

Objective:To evaluate the health benefits and intervention efficiency of different strategies of initiating antihypertensive therapy for the primary prevention of cardiovascular diseases in a community-based Chinese population from the Chinese electronic health records research in Yinzhou(CHERRY)study.Methods:A decision-analytic Markov model was used to simulate and compare different antihy-pertensive initiation strategies,including:Strategy 1,initiation of antihypertensive therapy for Chinese adults with systolic blood pressure(SBP)≥140 mmHg(2020 Chinese guideline on the primary preven-tion of cardiovascular diseases);Strategy 2,initiation of antihypertensive therapy for Chinese adults with SBP≥130 mmHg;Strategy 3,initiation of antihypertensive therapy for Chinese adults with SBP ≥140 mmHg,or with SBP between 130 and 140 mmHg and at high risk of cardiovascular diseases(2017 American College of Cardiology/American Heart Association guideline for the prevention,detection,evaluation,and management of high blood pressure in adults);Strategy 4,initiation of antihypertensive therapy for Chinese adults with SBP≥ 160 mmHg,or with SBP between 140 and 160 mmHg and at high risk of car-diovascular diseases(2019 United Kingdom National Institute for Health and Care Excellence guideline for the hypertension in adults:Diagnosis and management).The high 10-year cardiovascular risk was de-fined as the predicted risk over 10％based on the 2019 World Health Organization cardiovascular disease risk charts.Different strategies were simulated by the Markov model for ten years(cycles),with parame-ters mainly from the CHERRY study or published literature.After ten cycles of simulation,the numbers of quality-adjusted life years(QALY),cardiovascular events and all-cause deaths were calculated to evaluate the health benefits of each strategy,and the numbers needed to treat(NNT)for each cardiovas-cular event or all-cause death could be prevented were calculated to assess the intervention efficiency.One-way sensitivity analysis on the uncertainty of incidence rates of cardiovascular disease and probabilis-tic sensitivity analysis on the uncertainty of hazard ratios of interventions were conducted.Results:A to-tal of 213 987 Chinese adults aged 35-79 years without cardiovascular diseases were included.Com-pared with strategy 1,the number of cardiovascular events that could be prevented in strategy 2 increased by 666(95％UI:334-975),while the NNT per cardiovascular event prevented increased by 10(95％UI:7-20).In contrast to strategy 1,the number of cardiovascular events that could be prevented in strategy 3 increased by 388(95％UI:194-569),and the NNT per cardiovascular event prevented decreased by 6(95％UI:4-12),suggesting that strategy 3 had better health benefits and intervention efficiency.Compared to strategy 1,although the number of cardiovascular events that could be prevented decreased by 193(95％UI:98-281)in strategy 4,the NNT per cardiovascular event prevented decreased by 18(95％UI:13-37)with better efficiency.The results were consistent in the sensitivity analyses.Conclusion:When initiating antihypertensive therapy in an economically developed area of China,the strategy combined with cardiovascular risk assessment is more efficient than those purely based on the SBP threshold.The cardiovascular risk assessment strategy with different SBP thresholds is suggested to balance health benefits and intervention efficiency in diverse populations.

Objective To investigate the protective effect and mechanism of CDK4/6 inhibitor palbociclib against radiation-induced injury in rats'small intestinal crypt epithelial cell line(IEC-6).Methods(1)Using CCK-8 colorimetric assay,colony formation assay,the PI staining method,Annexin V-FITC/PI dual staining and Western blot,the impact of palbociclib on proliferation,cell cycle dynamics,apoptosis,DNA damage,as well as phosphorylation events at Rb-780 and 795 sites in irradiated IEC-6 cells was investigated.(2)An IEC-6 cell line overexpressing Rb was established,and the effects of Rb overexpression on proliferation,cell cycle,and apoptosis in the IEC-6 cell line were assessed using the CCK-8 colorimetric assay,PI staining method,Annexin V-PE/7-AAD dual staining and Western blot.Additionally,the impact of Rb overexpression on the protective effect of palbociclib against radiation damage was verified in the Rb-overexpressing IEC-6 cell line.Results(1)Administration of palbociclib was demonstrated to enhance the proliferative capacity of IEC-6 cells following exposure to 10 Gy X-ray irradiation,increase colony formation ability post 4-8 Gy X-ray exposure while concomitantly reducing the proportion of cells in the G2/M phase after 10 Gy irradiation and diminishing apoptosis in irradiated IEC-6 cells.Protein expression analysis revealed that palbociclib inhibited phosphorylation at Rb-780 and 795 sites and attenuated the production of γ-H2AX in IEC-6 cells following irradiation.(2)After transfection of IEC-6 cells with Rb overexpression lentivirus,there was a significant increase in the total protein expression of Rb.The phosphorylation levels at Rb-780 and 795 sites were markedly elevated.Consequently,cell proliferation was accelerated,the proportion of cells in the S phase of the cell cycle increased,and the apoptotic rate significantly rose after exposure to 10 Gy X-ray irradiation.(3)Treatment with a lower dose of palbociclib(0.05 μmol/L)was found to suppress the phosphorylation of Rb at 780 and 795 sites in IEC-6 cells overexpressing Rb.Additionally,it reduced apoptosis in IEC-6 cells overexpressing Rb following exposure to 10 Gy X-ray irradiation.However,this treatment did not inhibit the phosphorylation of Rb at 780 and 795 sites in IEC-6 cells transfected with the empty vector,nor did it exert a protective effect against radiation-induced damage in these cells.Conclusion The CDK4/6 inhibitor palbociclib demonstrates significant protective effects against radiation-induced damage in rats'intestinal crypt epithelial cell line(IEC-6),with the Rb protein potentially playing a crucial role in mediating this radioprotective response.

Objective:Survival analysis of cancers' incidence data in Tianjin from 2010 to 2016 was conducted to provide the basis for formulating and evaluating regional health policies on cancer prevention and treatment.Methods:Registration data in Tianjin were used between January 1, 2010 to December 31, 2016 and patients were followed-up till 31 December, 2021. Life-table method was used to calculate the observed survival rate and Edered Ⅱ was used to calculate the relative survival rate. The data were stratified by year, gender, age group and cancer sites. Difference in survival curves between group was analyzed by Kaplan-Meier method and Log rank test. Joinpoint regression model was used to analyze the trend change.Results:The 5-year relative survival rates of cancer were 41.92% to 53.65% from 2010 to 2016 for residents in Tianjin, with an increasing trend ( t=4.81 ,P=0.005), and the average was 48.56%. The survival rate of females was higher than that of males (57.71%vs. 39.20%), and the survival rate of urban residents was higher than that of rural residents (49.38% vs. 47.24%). The 5-year relative survival rates were 63.14%, 78.39%, 58.25% and 32.67% in 0-14, 15-44, 45-64 and 65 and above age groups, respectively. The median relative survival times of all cancer were 2.34 to 6.00 years from 2010 to 2016 in Tianjin, with an increasing trend ( t=3.86, P=0.012). The average of median relative survival times was 4.11 years. The median survival time of females was longer than that of males (11.99 years vs. 2.03 years), and the time of urban residents were longer than that of rural residents (4.60 years vs. 3.43 years). The median relative survival time were 12.07, 11.92 and 1.34 years in 15-44, 45-64 and 65 and above age groups, respectively. Conclusions:The cumulative survival rate of cancer increased significantly from 2010 to 2016 in Tianjin, indicating that the prevention and treatment effect of cancer is obvious. The focus should be on male, rural areas, higher age group, and targeted prevention and treatment measures should be taken to lung, esophagus, liver, gallbladder and pancreatic cancer.

Objective:To explore the trends and distribution of liver cancer between sexes, ages, and urban-rural areas in Tianjin, China from 1999 to 2021, and provide data for targeted prevention and control strategies of liver cancer in Tianjin.Methods:Liver cancer mortality data of Tianjin during 1999-2021 were from the Tianjin population based mortality surveillance system maintained by the Tianjin Centers for Disease Control and Prevention (CDC), and the population data of permanent Tianjin residents were from Tianjin Municipal Public Security Bureau. Liver cancer mortality, years of life lost (YLL), years lived with disability (YLD), and disability adjusted life years (DALY) were calculated using the cause of death surveillance data collected by Tianjin Centers for Disease Control and Prevention. The distributions of these data among residents of different sexes, ages, and regions were analyzed. Segi's world standard population was used for standardization. Joinpoint regression was used for trend analysis on the mortality rate of liver cancer and the disease burden.Results:The liver cancer mortality rate in Tianjin decreased by 46.75% from 1999 to 2021, with distinct phased characteristics. From 1999 to 2010, the age-sex-standardized mortality rate (SMR) decreased from 12.62/100 000 to 11.64/100 000 with an annual percent change (APC) of -1.32% ( P=0.003). From 2010 to 2021, the SMR decreased from 11.64/100 000 to 6.72/100 000 (APC=-3.89%, P＜0.001). The age-sex-standardized DALY rates(SDR) decreased by 50.63% from 1999 to 2021, also with distinct phased characteristics. From 1999 to 2010, the SDR decreased from 388.67/100 000 to 349.38/100 000 (APC=-1.35%, P=0.002). From 2010 to 2021, the SDR decreased from 349.38/100 000 to 191.88/100 000 (APC=-4.43%, P＜0.001). The liver cancer mortality rate declined most rapidly in the age group under 45 years; the APC for those under 35 years was -5.07% ( P＜0.001), and for those aged 35-44 years, the APC was 0.63% ( P=0.707) and -8.21% ( P＜0.001) before and after 2007, respectively. Both SMR and SDR were significantly higher in males than in females ( P＜0.01). Both SMR and SDR were significantly higher in urban areas than in rural areas from 1999 to 2007 ( P＜0.05), but they became similar after 2008. Liver cancer DALY are predominantly YLL, accounting for 99%. The median age of liver cancer deaths in Tianjin during 1999-2021 was 64-68 years old, with males lower than females ( P＜0.05), and rural areas lower than urban areas ( P＜0.05), generally showing an increasing trend (1999-2014: APC=0.11%, P=0.047; 2014-2021: APC=0.51%, P=0.005). Conclusions:Liver cancer mortality rate and disease burden decreased from 1999 to 2021 in Tianjin, with an especially accelerated decline after 2010. Further efforts to reduce liver cancer mortality in Tianjin are needed, and special attention should be focused on the elderly, male, and rural residents.