OBJECTIVES: To verify whether hesperetin (Hes) alleviates doxorubicin (DOX)-induced cardiotoxicity by reducing inflammation via regulating the AMPK/NLRP3 pathway. METHODS: C57/bl6 mice and H9c2 cells treated with DOX to mimic cardiotoxicity were randomly divided into Sham (or control) group, DOX group, DOX+Hes group, DOX+Hes+compound C (CC, an AMPK inhibitor) group. Cardiac function and myocardial pathologies of the mice were evaluated, and the changes in H9c2 cell morphology and viability were assessed. Lactate dehydrogenase (LDH) activity in mouse myocardial tissues and H9c2 cells was measured using ELISA, and H9c2 cell apoptosis was detected with TUNEL staining. In both H9c2 cells and the myocardial tissues of the mice, cellular expression levels of TNF-α, IL-6 and IL-1β mRNAs and cleaved caspase-3, Bcl2, Bax, IL-1β, IL-18, p-AMPK, AMPK, p-mTOR, mTOR, NLRP3, ASC and caspase-1 proteins were detected using RT-PCR and Western blotting. RESULTS: DOX treatment caused cell swelling, decreased cell viability and increased LDH activity in H9c2 cells, resulting also in significantly increased cell apoptosis and cleaved caspase-3 expression and decreased Bcl2/Bax ratio. The DOX-treated mice showed obvious myocardial fiber swelling and inflammatory infiltration, decreased cardiac function and significantly increased myocardial LDH activity. In H9c2 cells, DOX treatment significantly increased the mRNA expressions of TNF-α, IL-6 and IL-1β and protein expressions of IL-1β and IL-18, lowered the expressions of p-AMPK and p-mTOR, and increased the expressions of NLRP3, ASC and caspase-1. Hes treatment obviously reduced these toxic effects of DOX in H9c2 cells, but its protective effects were blocked by application of compound C. CONCLUSIONS Hes reduces DOX-induced cardiotoxicity by inhibiting inflammation via regulating the AMPK/NLRP3 pathway.
Animals ; Doxorubicin/toxicity* ; NLR Family, Pyrin Domain-Containing 3 Protein/metabolism* ; Mice, Inbred C57BL ; Mice ; Signal Transduction/drug effects* ; Cardiotoxicity ; AMP-Activated Protein Kinases/metabolism* ; Apoptosis/drug effects* ; Cell Line ; Myocytes, Cardiac/drug effects* ; Rats

Objective To conduct a scoping review of the application of gamification programs in exercise rehabilitation for knee osteoarthritis,examining the application carriers,game content,outcome indicators,measurement tools,and application effects of gamification programs,to provide references for future practice and related research in this field.Methods The search was conducted in PubMed,Web of Science,Cochrane Library,Scopus,CIN AHL,China National Knowledge Infrastructure,CNKI,and Wanfang Data from their inception to December 28,2024.The included studies were summarized and analyzed.Results A total of 28 studies were included in the review.The game carriers encompassed virtual reality technology,sensor devices,and mobile applications.The game content covered interactive motion games,aerobic exercises,and goal-motivated games.Outcome indicators included functional performance,physical activity,pain,psychological and health status,and user experience.Gamification programs were found to effectively enhance user engagement,improve physical function,reduce negative emotions,and improve quality of life.However,there remains controversy regarding their efficacy in pain relief.Conclusion Gamification programs have shown positive effects in exercise rehabilitation for knee osteoarthritis.Future efforts should focus on developing gamification programs that are culturally appropriate for China,creating"digital therapeutics",continuously updating systems,conducting economic evaluations,and ensuring digital equity to enhance patients'rehabilitation experiences and improve health outcomes.

BACKGROUND: Stroke is the leading cause of death and long-term disability worldwide, including China. This study aimed to provide timely updates on stroke burden and stroke-related risk factors to help improve population-based prevention and control strategies. METHODS: Based on the Global Burden of Disease study 2021, incidence rate, prevalence rate, mortality rate, and disability-adjusted life-year (DALY) rate were used to estimate stroke burden trend from 1990 to 2021. RESULTS: In 2021, China had 4.1 million incident stroke cases, 26.3 million prevalent stroke cases, 2.6 million stroke related deaths, and 53.2 million stroke related DALYs, compared to 11.9 million incident stroke cases, 93.8 million prevalent stroke cases, 7.3 million stroke related deaths, and 160.5 million stroke-related DALYs worldwide. In 2021, the top six risk factors contributing to stroke burden were high blood pressure, air pollution, tobacco consumption, dietary risk factors, high low-density lipoprotein cholesterol, and high fasting plasma glucose, both in China and worldwide. From 1990 to 2021, China had significant increases of incidence rate, prevalence rate, mortality rate, and DALY rate for stroke, with estimates of 100.6 (95% uncertainty intervals [UI]: 87.2, 114.1)%, 102.9 (95% UI: 95.5, 110.9)%, 40.0 (95% UI: 14.9, 72.3)% and 15.7 (95% UI: -4.6, 41.2)%, respectively, while global incidence rate, prevalence rate, mortality rate and DALY rate for total stroke showed relatively moderate increases or even decreases, with estimates of 15.0 (95% UI: 12.1,18.0)%, 25.8 (95% UI: 23.7, 28.0)%, -2.6 (95% UI: -10.6, 5.5)%, and -10.7 (95% UI: -17.7, -3.6)%, respectively. CONCLUSION Stroke remains a huge disease burden worldwide and in China, and compared to the worldwide China has a significantly higher burden of stroke.
Humans ; Stroke/etiology* ; China/epidemiology* ; Risk Factors ; Global Burden of Disease ; Disability-Adjusted Life Years ; Prevalence ; Incidence ; Female ; Quality-Adjusted Life Years ; Male

Objective To explore the objective facial appearance characteristics of patients with coronary heart disease(CHD).Methods From April 7,2019 to December 1,2022,313 patients with CHD were recruited from Dongzhimen Hospital,Beijing University of Chinese Medicine,Dongfang Hospital,Beijing University of Chinese Medicine,and the First Affiliated Hospital of Hunan University of Chinese Medicine,together with 293 healthy controls.Standardized facial images were obtained using the tongue-face diagnostic instrument.The face was divided into six regions:the forehead,left cheek,right cheek,nose,lips,and chin.Nine color parameters were extracted from each region,including red(R),green(G),blue(B),hue(H),saturation(S),value(V),lightness(L),red-green axis(a),and yellow-blue axis(b).Comparisons between groups were performed.Results Compared with the healthy group,in the forehead region,values of R,S,V,a,and b were higher in the coronary heart disease group,whereas B was lower(P<0.05);in the left cheek,nose,and chin regions,R,G,B,V,and L decreased,whereas S,a,and b increased(P<0.05);in the right cheek region,R,G,B,H,V,and L decreased,while S,a,and b increased(P<0.05);in the lips region,R,G,B,H,V,L,and a decreased,whereas S and b increased(P<0.05).Conclusion Compared with healthy individuals,patients with CHD present with a darker,more saturated facial complexion with reduced brightness,overall manifesting as"dark red complexion"and"dense but not bright color,"suggesting the pathogenesis of qi and blood circulation stagnation and internal blood stasis retention.The objective expression of facial features may have greater application value in syndrome differentiation and auxiliary diagnosis in traditional Chinese medicine.

Objective:To explore the efficacy of non-invasive prenatal testing (NIPT) of fetal free DNA in maternal peripheral blood in fetuses with increased nuchal translucency (NT).Methods:A retrospective analysis was conducted on 1 184 singleton pregnant women that underwent chromosomal microarray analysis (CMA) at Nanjing Drum Tower Hospital, Nanjing University Medical School from June 2014 to December 2022 due to fetal increased NT (≥3.0 mm). These subjects were categorized based on whether the increased NT was accompanied by other high-risk factors into isolated increased NT without advanced maternal age (further subdivided into 3.0 mm≤NT<3.5 mm, 3.5 mm≤NT<4.0 mm, and NT≥4.0 mm subgroups), isolated increased NT with advanced maternal age, increased NT with nasal bone abnormalities, increased NT with other soft markers, and increased NT with structural abnormalities groups. Assuming the sensitivity and specificity of NIPT and expanded NIPT at this center were both 100%, genomic abnormalities outside the detection range of NIPT or expanded NIPT were termed as residual risk of NIPT or expanded NIPT. Chi-square test and Bonferroni correction were used to compare the residual risks of NIPT and expanded NIPT among the three subgroups of isolated increased NT without advanced maternal age group. Results:(1) In the group of isolated increased NT without advanced maternal age: For the 3.0 mm≤NT<3.5 mm subgroup (329 cases), 19 abnormalities were detected by CMA [12 cases of chromosome aneuploidy, seven cases of pathogenic copy number variation (pCNV)], with residual risks of NIPT and expanded NIPT both at 2.1% (7/329). For the 3.5 mm≤NT<4.0 mm subgroup (173 cases), 29 abnormalities were detected by CMA (17 cases of chromosome aneuploidy, nine cases of pCNV, three cases of chromosome unbalanced translocation), with residual risks of NIPT at 8.1% (14/173) and expanded NIPT at 7.5% (13/173). For the NT≥4.0 mm subgroup (270 cases), CMA detected abnormalities in 70 cases (50 cases of chromosome aneuploidy, 16 cases of pCNV, three cases of unbalanced translocations, and one case of sex chromosome abnormality combined with pCNV). The residual risk of NIPT was 12.2% (33/270), and the residual risk of expanded NIPT was 7.0% (19/270). The residual risks of NIPT and expanded NIPT in the 3.0 mm≤NT<3.5 mm subgroup were lower than those in the 3.5 mm≤NT<4.0 mm and NT≥4.0 mm subgroups (Bonferroni correction, all P<0.017). (2) In the group of 92 cases with isolated increased NT and advanced maternal age, CMA detected abnormalities in 36 cases (29 cases of chromosome aneuploidy, five cases of pCNV, one case of trisomy 21 combined with sex chromosome abnormality, and one case of trisomy 18 combined with sex chromosome abnormality). The residual risk of NIPT was 7.6% (7/92), and that of expanded NIPT was 5.4% (5/92). (3) In the group of 49 cases with increased NT combined with nasal bone abnormalities, CMA detected abnormalities in 24 cases (23 cases of chromosome aneuploidy and one case of pCNV). The residual risks of NIPT and expanded NIPT were both 2.0% (1/49). (4) In the group of 26 cases with increased NT combined with other soft markers, CMA detected abnormalities in nine cases (six cases of chromosome aneuploidy, one case of pCNV, and two cases of chromosome unbalanced translocations). The residual risks of NIPT and expanded NIPT were both 11.5% (3/26). (5) In the group of 245 cases with increased NT combined with structural abnormalities, CMA detected abnormalities in 121 cases (107 cases of chromosome aneuploidy, seven cases of pCNV, four cases of chromosome unbalanced translocations, one case of trisomy 21 combined with trisomy 20, and two cases of trisomy 18 combined with sex chromosome abnormalities). The residual risk of NIPT was 16.7% (41/245), and that of expanded NIPT was 4.1% (10/245). Conclusions:For isolated NT≥3.5 mm or NT≥3.0 mm combined with other high-risk factors, chorionic villus sampling in early pregnancy can be recommended, advancing the timing of prenatal diagnosis from the second trimester to the first trimester. For fetuses with isolated 3.0 mm≤NT<3.5 mm, the 2.1% residual risk of chromosomal abnormalities should be fully informed during counseling, even if the risk of NIPT is low.

Objective:To predict pre-treatment clinical parameters that are associated with poor response and prognosis to ursodeoxycholic acid (UDCA) in patients with primary biliary cholangitis (PBC) and to use second-line treatment drugs in the early stages to delay the progression of the disease so that patients can benefit from early-stage treatment.Methods:Patients diagnosed with PBC at the Second Affiliated Hospital of Kunming Medical University from 2013 to 2022 were collected. Two hundred fifty-seven cases were screened in accordance with the inclusion and exclusion criteria. The response and prognosis conditions one year after treatment were followed up in outpatient and inpatient departments, as well as through telephone calls. Statistical analyses were performed using t-tests, Mann-Whitney U test, χ2 test, Fisher's exact test, and logistic regression analysis according to different data. Results:A total of 257 PBC cases were included, with 223 females (86.80%) and 34 males (13.20%). Univariate and multivariate binary logistic regression analyses showed that baseline high albumin levels [odds ratio ( OR): 0.882, 95% confidence interval ( CI): 0.805～0.967, P=0.008] were a protective factor for PBC patients' response to UDCA treatment after adjusting for different confounding factors, while baseline high alkaline phosphatase ( OR: 1.012, 95% CI: 1.008～1.016, P<0.001) and baseline high neutrophil/lymphocyte ratio (NLR) level ( OR: 1.462, 95% CI:1.079～1.981, P=0.014) were risk factors for a poor response to UDCA. Trend analysis showed that the baseline NLR quantile was positively correlated with the risk of poor response to UDCA ( OR: 5.512, 95% CI: 1.040～29.216, P=0.045) in patients with PBC. Cox proportional hazards regression analysis identified that age [hazard ratio ( HR): 1.050, 95% CI: 1.019～1.082] and NLR value ( HR:1.089, 95% CI:1.021～1.161) were independent influencing risk factors for all-cause mortality in PBC patients ( P<0.05). Conclusion:Baseline high albumin levels are protective factors against a poor biochemical response to UDCA, while baseline high alkaline phosphatase levels and high NLR are risk factors for a poor biochemical response to UDCA in patients with PBC. Additionally, baseline high NLR values are positively correlated with poor biochemical response to UDCA treatment.

Objective To explore the objective facial appearance characteristics of patients with coronary heart disease(CHD).Methods From April 7,2019 to December 1,2022,313 patients with CHD were recruited from Dongzhimen Hospital,Beijing University of Chinese Medicine,Dongfang Hospital,Beijing University of Chinese Medicine,and the First Affiliated Hospital of Hunan University of Chinese Medicine,together with 293 healthy controls.Standardized facial images were obtained using the tongue-face diagnostic instrument.The face was divided into six regions:the forehead,left cheek,right cheek,nose,lips,and chin.Nine color parameters were extracted from each region,including red(R),green(G),blue(B),hue(H),saturation(S),value(V),lightness(L),red-green axis(a),and yellow-blue axis(b).Comparisons between groups were performed.Results Compared with the healthy group,in the forehead region,values of R,S,V,a,and b were higher in the coronary heart disease group,whereas B was lower(P<0.05);in the left cheek,nose,and chin regions,R,G,B,V,and L decreased,whereas S,a,and b increased(P<0.05);in the right cheek region,R,G,B,H,V,and L decreased,while S,a,and b increased(P<0.05);in the lips region,R,G,B,H,V,L,and a decreased,whereas S and b increased(P<0.05).Conclusion Compared with healthy individuals,patients with CHD present with a darker,more saturated facial complexion with reduced brightness,overall manifesting as"dark red complexion"and"dense but not bright color,"suggesting the pathogenesis of qi and blood circulation stagnation and internal blood stasis retention.The objective expression of facial features may have greater application value in syndrome differentiation and auxiliary diagnosis in traditional Chinese medicine.

Objective:To explore the efficacy of non-invasive prenatal testing (NIPT) of fetal free DNA in maternal peripheral blood in fetuses with increased nuchal translucency (NT).Methods:A retrospective analysis was conducted on 1 184 singleton pregnant women that underwent chromosomal microarray analysis (CMA) at Nanjing Drum Tower Hospital, Nanjing University Medical School from June 2014 to December 2022 due to fetal increased NT (≥3.0 mm). These subjects were categorized based on whether the increased NT was accompanied by other high-risk factors into isolated increased NT without advanced maternal age (further subdivided into 3.0 mm≤NT<3.5 mm, 3.5 mm≤NT<4.0 mm, and NT≥4.0 mm subgroups), isolated increased NT with advanced maternal age, increased NT with nasal bone abnormalities, increased NT with other soft markers, and increased NT with structural abnormalities groups. Assuming the sensitivity and specificity of NIPT and expanded NIPT at this center were both 100%, genomic abnormalities outside the detection range of NIPT or expanded NIPT were termed as residual risk of NIPT or expanded NIPT. Chi-square test and Bonferroni correction were used to compare the residual risks of NIPT and expanded NIPT among the three subgroups of isolated increased NT without advanced maternal age group. Results:(1) In the group of isolated increased NT without advanced maternal age: For the 3.0 mm≤NT<3.5 mm subgroup (329 cases), 19 abnormalities were detected by CMA [12 cases of chromosome aneuploidy, seven cases of pathogenic copy number variation (pCNV)], with residual risks of NIPT and expanded NIPT both at 2.1% (7/329). For the 3.5 mm≤NT<4.0 mm subgroup (173 cases), 29 abnormalities were detected by CMA (17 cases of chromosome aneuploidy, nine cases of pCNV, three cases of chromosome unbalanced translocation), with residual risks of NIPT at 8.1% (14/173) and expanded NIPT at 7.5% (13/173). For the NT≥4.0 mm subgroup (270 cases), CMA detected abnormalities in 70 cases (50 cases of chromosome aneuploidy, 16 cases of pCNV, three cases of unbalanced translocations, and one case of sex chromosome abnormality combined with pCNV). The residual risk of NIPT was 12.2% (33/270), and the residual risk of expanded NIPT was 7.0% (19/270). The residual risks of NIPT and expanded NIPT in the 3.0 mm≤NT<3.5 mm subgroup were lower than those in the 3.5 mm≤NT<4.0 mm and NT≥4.0 mm subgroups (Bonferroni correction, all P<0.017). (2) In the group of 92 cases with isolated increased NT and advanced maternal age, CMA detected abnormalities in 36 cases (29 cases of chromosome aneuploidy, five cases of pCNV, one case of trisomy 21 combined with sex chromosome abnormality, and one case of trisomy 18 combined with sex chromosome abnormality). The residual risk of NIPT was 7.6% (7/92), and that of expanded NIPT was 5.4% (5/92). (3) In the group of 49 cases with increased NT combined with nasal bone abnormalities, CMA detected abnormalities in 24 cases (23 cases of chromosome aneuploidy and one case of pCNV). The residual risks of NIPT and expanded NIPT were both 2.0% (1/49). (4) In the group of 26 cases with increased NT combined with other soft markers, CMA detected abnormalities in nine cases (six cases of chromosome aneuploidy, one case of pCNV, and two cases of chromosome unbalanced translocations). The residual risks of NIPT and expanded NIPT were both 11.5% (3/26). (5) In the group of 245 cases with increased NT combined with structural abnormalities, CMA detected abnormalities in 121 cases (107 cases of chromosome aneuploidy, seven cases of pCNV, four cases of chromosome unbalanced translocations, one case of trisomy 21 combined with trisomy 20, and two cases of trisomy 18 combined with sex chromosome abnormalities). The residual risk of NIPT was 16.7% (41/245), and that of expanded NIPT was 4.1% (10/245). Conclusions:For isolated NT≥3.5 mm or NT≥3.0 mm combined with other high-risk factors, chorionic villus sampling in early pregnancy can be recommended, advancing the timing of prenatal diagnosis from the second trimester to the first trimester. For fetuses with isolated 3.0 mm≤NT<3.5 mm, the 2.1% residual risk of chromosomal abnormalities should be fully informed during counseling, even if the risk of NIPT is low.

Objective To conduct a scoping review of the application of gamification programs in exercise rehabilitation for knee osteoarthritis,examining the application carriers,game content,outcome indicators,measurement tools,and application effects of gamification programs,to provide references for future practice and related research in this field.Methods The search was conducted in PubMed,Web of Science,Cochrane Library,Scopus,CIN AHL,China National Knowledge Infrastructure,CNKI,and Wanfang Data from their inception to December 28,2024.The included studies were summarized and analyzed.Results A total of 28 studies were included in the review.The game carriers encompassed virtual reality technology,sensor devices,and mobile applications.The game content covered interactive motion games,aerobic exercises,and goal-motivated games.Outcome indicators included functional performance,physical activity,pain,psychological and health status,and user experience.Gamification programs were found to effectively enhance user engagement,improve physical function,reduce negative emotions,and improve quality of life.However,there remains controversy regarding their efficacy in pain relief.Conclusion Gamification programs have shown positive effects in exercise rehabilitation for knee osteoarthritis.Future efforts should focus on developing gamification programs that are culturally appropriate for China,creating"digital therapeutics",continuously updating systems,conducting economic evaluations,and ensuring digital equity to enhance patients'rehabilitation experiences and improve health outcomes.

Objective:To predict pre-treatment clinical parameters that are associated with poor response and prognosis to ursodeoxycholic acid (UDCA) in patients with primary biliary cholangitis (PBC) and to use second-line treatment drugs in the early stages to delay the progression of the disease so that patients can benefit from early-stage treatment.Methods:Patients diagnosed with PBC at the Second Affiliated Hospital of Kunming Medical University from 2013 to 2022 were collected. Two hundred fifty-seven cases were screened in accordance with the inclusion and exclusion criteria. The response and prognosis conditions one year after treatment were followed up in outpatient and inpatient departments, as well as through telephone calls. Statistical analyses were performed using t-tests, Mann-Whitney U test, χ2 test, Fisher's exact test, and logistic regression analysis according to different data. Results:A total of 257 PBC cases were included, with 223 females (86.80%) and 34 males (13.20%). Univariate and multivariate binary logistic regression analyses showed that baseline high albumin levels [odds ratio ( OR): 0.882, 95% confidence interval ( CI): 0.805～0.967, P=0.008] were a protective factor for PBC patients' response to UDCA treatment after adjusting for different confounding factors, while baseline high alkaline phosphatase ( OR: 1.012, 95% CI: 1.008～1.016, P<0.001) and baseline high neutrophil/lymphocyte ratio (NLR) level ( OR: 1.462, 95% CI:1.079～1.981, P=0.014) were risk factors for a poor response to UDCA. Trend analysis showed that the baseline NLR quantile was positively correlated with the risk of poor response to UDCA ( OR: 5.512, 95% CI: 1.040～29.216, P=0.045) in patients with PBC. Cox proportional hazards regression analysis identified that age [hazard ratio ( HR): 1.050, 95% CI: 1.019～1.082] and NLR value ( HR:1.089, 95% CI:1.021～1.161) were independent influencing risk factors for all-cause mortality in PBC patients ( P<0.05). Conclusion:Baseline high albumin levels are protective factors against a poor biochemical response to UDCA, while baseline high alkaline phosphatase levels and high NLR are risk factors for a poor biochemical response to UDCA in patients with PBC. Additionally, baseline high NLR values are positively correlated with poor biochemical response to UDCA treatment.