A mounting body of research suggests that circRNAs significantly contribute to the develop-ment of myocardial fibrosis.The microarray results of human circular RNA expression profile indicated that circHERC4_041 expression increased in the myocardium of patients with heart failure,RT-qPCR a-nalysis confirmed that the myocardial expression level of circHERC4_041 in individuals with heart failure were considerably elevated compared to that in healthy organ donors.Fluorescence in situ hybridization(FISH)confirmed that circHERC4_041 was abundant in the cytoplasm of human cardiomyocyte AC16.Overexpression of circHERC4_041 in mouse myocardial fibroblasts(mCFs)mediated by adenovirus in-hibited the expression of fibrosis-related proteins in mCFs.Experiments involving cell proliferation,wound healing,and Transwell assays demonstrated that overexpression of circHERC4_041 suppressed the growth and mobility of mCFs(P＜0.001).Sequence analysis results suggested that circHERC4_041 con-tains potential ribosome entry sequence(IRES)and open reading frame(ORF).Western blot confirmed that circHERC4_041 could translate the 516 amino acid HERC4-516aa protein,which was mainly located in the cytoplasm of the cell.Cell functional experiments confirmed that circHERC4_041 inhibited the fi-brotic phenotype of mCFs by specifically translating HERC4-516aa(P＜0.05).The specific interaction between HERC4-516aa and transglutaminase 2(TGM2)was confirmed by IP-MS screening and Co-IP i-dentification.Further results found that the degradation of TGM2 was promoted through proteasome path-way.The overexpression of TGM2 in mCFs facilitated by adenoviral vectors could counteract the suppres-sive effects of HERC4-516aa on the fibrotic phenotype of mCFs.Therefore,this study confirmed that the HERC4-516aa protein translated by circHERC4_041 can specifically bind to TGM2 to inhibit the fibrotic phenotype of myocardial fibroblasts.

A mounting body of research suggests that circRNAs significantly contribute to the develop-ment of myocardial fibrosis.The microarray results of human circular RNA expression profile indicated that circHERC4_041 expression increased in the myocardium of patients with heart failure,RT-qPCR a-nalysis confirmed that the myocardial expression level of circHERC4_041 in individuals with heart failure were considerably elevated compared to that in healthy organ donors.Fluorescence in situ hybridization(FISH)confirmed that circHERC4_041 was abundant in the cytoplasm of human cardiomyocyte AC16.Overexpression of circHERC4_041 in mouse myocardial fibroblasts(mCFs)mediated by adenovirus in-hibited the expression of fibrosis-related proteins in mCFs.Experiments involving cell proliferation,wound healing,and Transwell assays demonstrated that overexpression of circHERC4_041 suppressed the growth and mobility of mCFs(P＜0.001).Sequence analysis results suggested that circHERC4_041 con-tains potential ribosome entry sequence(IRES)and open reading frame(ORF).Western blot confirmed that circHERC4_041 could translate the 516 amino acid HERC4-516aa protein,which was mainly located in the cytoplasm of the cell.Cell functional experiments confirmed that circHERC4_041 inhibited the fi-brotic phenotype of mCFs by specifically translating HERC4-516aa(P＜0.05).The specific interaction between HERC4-516aa and transglutaminase 2(TGM2)was confirmed by IP-MS screening and Co-IP i-dentification.Further results found that the degradation of TGM2 was promoted through proteasome path-way.The overexpression of TGM2 in mCFs facilitated by adenoviral vectors could counteract the suppres-sive effects of HERC4-516aa on the fibrotic phenotype of mCFs.Therefore,this study confirmed that the HERC4-516aa protein translated by circHERC4_041 can specifically bind to TGM2 to inhibit the fibrotic phenotype of myocardial fibroblasts.

OBJECTIVE To observe the effect of electroacupuncture on insomnia symptoms and blood pressure levels in patients with hypertension and insomnia.METHODS A randomized controlled clinical trial was conducted.A total of 60 patients with hyper-tension and insomnia were enrolled in Jiangsu Province Hospital of Chinese Medicine from December 2021 to December 2022 and ran-domly divided into a treatment group and a control group at a ratio of 1:1,with 30 cases in each group.During the treatment period,2 cases dropped out of the control group and 1 case dropped out of the treatment group.Both groups of patients received sleep and hy-pertension health education and conventional hypertension drug treatment.The treatment group was given electroacupuncture interven-tion,and the control group was given sham electroacupuncture intervention.The treatment course of both groups was 4 weeks.Before and after treatment,the Pittsburgh Sleep Quality Index(PSQI),Insomnia Severity Index(ISI)scale and portable polysomnography(PPSG)were used to evaluate the changes in sleep quality of the two groups of patients;home blood pressure measurement(HBPM)was adopted to evaluate the changes in blood pressure levels of the two groups of patients.Spearman correlation analysis and linear re-gression analysis were used to study the relationship between blood pressure levels and PPSG parameters.RESULTS After treatment,only the sleep onset latency(SOL)and sleep efficiency(SE)of the control group were significantly improved(P<0.05);the PSQI,ISI scores,morning and night systolic blood pressure(SBP),and diastolic blood pressure(DBP)of the treatment group were signifi-cantly reduced(P<0.01),which was better than that of the control group(P<0.05,P<0.01);the sleep parameters of PPSG were significantly improved(P<0.01),which was better than that of the control group(P<0.05,P<0.01).The results of Spearman corre-lation analysis showed that the morning SBP level of patients before treatment was related to the wake time after sleep onset(WASO)and the number of micro-arousals(MAS).After treatment,the decrease in the morning SBP of patients was related to the reduction of MAS and the shortening of SOL.CONCLUSION Electroacupuncture can effectively improve the insomnia symptoms and blood pres-sure levels of patients with hypertension.Its therapeutic mechanism may be related to reducing the number of MAS and improving the degree of sleep fragmentation.

OBJECTIVE To observe the effect of electroacupuncture on insomnia symptoms and blood pressure levels in patients with hypertension and insomnia.METHODS A randomized controlled clinical trial was conducted.A total of 60 patients with hyper-tension and insomnia were enrolled in Jiangsu Province Hospital of Chinese Medicine from December 2021 to December 2022 and ran-domly divided into a treatment group and a control group at a ratio of 1:1,with 30 cases in each group.During the treatment period,2 cases dropped out of the control group and 1 case dropped out of the treatment group.Both groups of patients received sleep and hy-pertension health education and conventional hypertension drug treatment.The treatment group was given electroacupuncture interven-tion,and the control group was given sham electroacupuncture intervention.The treatment course of both groups was 4 weeks.Before and after treatment,the Pittsburgh Sleep Quality Index(PSQI),Insomnia Severity Index(ISI)scale and portable polysomnography(PPSG)were used to evaluate the changes in sleep quality of the two groups of patients;home blood pressure measurement(HBPM)was adopted to evaluate the changes in blood pressure levels of the two groups of patients.Spearman correlation analysis and linear re-gression analysis were used to study the relationship between blood pressure levels and PPSG parameters.RESULTS After treatment,only the sleep onset latency(SOL)and sleep efficiency(SE)of the control group were significantly improved(P<0.05);the PSQI,ISI scores,morning and night systolic blood pressure(SBP),and diastolic blood pressure(DBP)of the treatment group were signifi-cantly reduced(P<0.01),which was better than that of the control group(P<0.05,P<0.01);the sleep parameters of PPSG were significantly improved(P<0.01),which was better than that of the control group(P<0.05,P<0.01).The results of Spearman corre-lation analysis showed that the morning SBP level of patients before treatment was related to the wake time after sleep onset(WASO)and the number of micro-arousals(MAS).After treatment,the decrease in the morning SBP of patients was related to the reduction of MAS and the shortening of SOL.CONCLUSION Electroacupuncture can effectively improve the insomnia symptoms and blood pres-sure levels of patients with hypertension.Its therapeutic mechanism may be related to reducing the number of MAS and improving the degree of sleep fragmentation.

Objective To investigate the effect of the combination of Hyssop and White Peony on the nuclear factor E2-related factor-2(Nrf2)/heme oxygenase-1(HO-1)signaling pathway induced by the combination of NG-nitro-L-arginine methyl ester,hydrochloride(L-NAME)and Aconite in mice with hypertensive kidney injury and its therapeutic mechanism.Methods A total of 80 KM mice were randomly divided into blank group,model group and experimental A,B,C,D,E and F groups,with 10 mice per group.Except for the blank group,the remaining 7 groups were given aconite decoction+L-NAME by gavage to prepare a hypertensive kidney injury model.Experimental A,B,C,D,E,and F groups were given 6.83 g·kg-1·d-1 of different proportions of Hyssop-White Peony solution in different proportions with 5∶0,4∶1,3∶2,2∶3,1∶4,0∶5,respectively.Blank and model groups were given an equal volume of distilled water by gavage.All 8 groups of mice were intervened for 6 weeks.The blood pressure changes of mice in each group were compared;the levels of blood urea nitrogen(BUN)in serum and superoxide dismutase(SOD)in kidney tissue were detected by kit;and the expression of Nrf2 and HO-1 in kidney tissue was detected by immunohistochemistry.Results The systolic blood pressure levels of blank group,model group and experimental C,D groups were(99.56±4.13),(140.11±7.33),(106.23±8.41)and(105.97±6.43)mmHg;the blood urea nitrogen contents were(172.00±15.90),(352.64±17.23),(201.76±12.14)and(192.72±12.77)μg·mL-1;BUN contents were(232.14±8.58),(165.44±6.17),(205.06±5.34)and(182.94±9.91)μg·mL-1;the expression levels(optical density)of Nrf2 were 2.06±0.14,2.25±0.22,2.63±0.22 and 2.83±0.21;the expression levels(optical density)of HO-1 were 2.18±0.12,2.25±0.10,2.64±0.16 and 2.65±0.28,respectively.The above indexes in experimental C and D groups were statistically significant compared with those of the model group(all P＜0.01).Conclusion Hyssop and White Peony can enhance the ability of L-NAME and Aconite to resist oxidative stress in mice with hypertensive kidney injury induced by the combination of Nrf2/HO-1 pathway,and inhibit the process of apoptosis of kidney cells caused by kidney injury caused by hypertension,thereby exerting its protective effect on the kidney.

Objective To investigate the effect of the combination of Hyssop and White Peony on the nuclear factor E2-related factor-2(Nrf2)/heme oxygenase-1(HO-1)signaling pathway induced by the combination of NG-nitro-L-arginine methyl ester,hydrochloride(L-NAME)and Aconite in mice with hypertensive kidney injury and its therapeutic mechanism.Methods A total of 80 KM mice were randomly divided into blank group,model group and experimental A,B,C,D,E and F groups,with 10 mice per group.Except for the blank group,the remaining 7 groups were given aconite decoction+L-NAME by gavage to prepare a hypertensive kidney injury model.Experimental A,B,C,D,E,and F groups were given 6.83 g·kg-1·d-1 of different proportions of Hyssop-White Peony solution in different proportions with 5∶0,4∶1,3∶2,2∶3,1∶4,0∶5,respectively.Blank and model groups were given an equal volume of distilled water by gavage.All 8 groups of mice were intervened for 6 weeks.The blood pressure changes of mice in each group were compared;the levels of blood urea nitrogen(BUN)in serum and superoxide dismutase(SOD)in kidney tissue were detected by kit;and the expression of Nrf2 and HO-1 in kidney tissue was detected by immunohistochemistry.Results The systolic blood pressure levels of blank group,model group and experimental C,D groups were(99.56±4.13),(140.11±7.33),(106.23±8.41)and(105.97±6.43)mmHg;the blood urea nitrogen contents were(172.00±15.90),(352.64±17.23),(201.76±12.14)and(192.72±12.77)μg·mL-1;BUN contents were(232.14±8.58),(165.44±6.17),(205.06±5.34)and(182.94±9.91)μg·mL-1;the expression levels(optical density)of Nrf2 were 2.06±0.14,2.25±0.22,2.63±0.22 and 2.83±0.21;the expression levels(optical density)of HO-1 were 2.18±0.12,2.25±0.10,2.64±0.16 and 2.65±0.28,respectively.The above indexes in experimental C and D groups were statistically significant compared with those of the model group(all P＜0.01).Conclusion Hyssop and White Peony can enhance the ability of L-NAME and Aconite to resist oxidative stress in mice with hypertensive kidney injury induced by the combination of Nrf2/HO-1 pathway,and inhibit the process of apoptosis of kidney cells caused by kidney injury caused by hypertension,thereby exerting its protective effect on the kidney.

Objective: We aimed to investigate whether 2-[ 18F]fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography (2-[ 18F]FDG PET/CT) can aid in evaluating the risk of malignancy in ampullary tumors detected by endoscopy. Materials and Methods: This single-center retrospective cohort study analyzed 155 patients (79 male, 76 female; mean age, 65.7 ± 12.7 years) receiving 2-[ 18F]FDG PET/CT for endoscopy-detected ampullary tumors 5–87 days (median, 7 days) after the diagnostic endoscopy between June 2007 and December 2020. The final diagnosis was made based on histopathological findings. The PET imaging parameters were compared with clinical data and endoscopic features. A model to predict the risk of malignancy, based on PET, endoscopy, and clinical findings, was generated and validated using multivariable logistic regression analysis and an additional bootstrapping method. The final model was compared with standard endoscopy for the diagnosis of ampullary cancer using the DeLong test. Results: The mean tumor size was 17.1 ± 7.7 mm. Sixty-four (41.3%) tumors were benign, and 91 (58.7%) were malignant. Univariable analysis found that ampullary neoplasms with a blood-pool corrected peak standardized uptake value in earlyphase scan (SUVe) ≥ 1.7 were more likely to be malignant (odds ratio [OR], 16.06; 95% confidence interval [CI], 7.13–36.18;P < 0.001). Multivariable analysis identified the presence of jaundice (adjusted OR [aOR], 4.89; 95% CI, 1.80–13.33; P = 0.002), malignant traits in endoscopy (aOR, 6.80; 95% CI, 2.41–19.20; P < 0.001), SUVe ≥ 1.7 in PET (aOR, 5.43; 95% CI, 2.00–14.72; P < 0.001), and PET-detected nodal disease (aOR, 5.03; 95% CI, 1.16–21.86; P = 0.041) as independent predictors of malignancy. The model combining these four factors predicted ampullary cancers better than endoscopic diagnosis alone (area under the curve [AUC] and 95% CI: 0.925 [0.874–0.956] vs. 0.815 [0.732–0.873], P < 0.001). The model demonstrated an AUC of 0.921 (95% CI, 0.816–0.967) in candidates for endoscopic papillectomy. Conclusion Adding 2-[ 18F]FDG PET/CT to endoscopy can improve the diagnosis of ampullary cancer and may help refine therapeutic decision-making, particularly when contemplating endoscopic papillectomy.

Objective:To investigate the protective effect and possible mechanism of sulforaphane (SFN) on acute liver injury in mice induced by diquat (DQ) poisoning.Methods:Forty-eight male C57BL/6 mice were divided into Control group, DQ model group (DQ group), SFN intervention group (DQ+SFN group), and SFN control group (SFN group) using a random number table method, with 12 mice in each group. Acute liver injury mice model was established by one-time intraperitoneal injection of 1 mL of 40 mg/kg DQ solution at once. SFN group was injected with 1 mL of ddH 2O. After 4 hours of molding, 0.5 mL of 5 mg/kg SFN solution was injected into the peritoneal cavity of the DQ+SFN group and SFN group, once daily for 7 consecutive days. DQ group and Control group were injected with an equal amount of ddH 2O. Then, the mice were euthanized to collect liver tissue and blood samples, and the levels of plasma biomarkers alanine aminotransferase (ALT) and aspartate aminotransferase (AST), as well as oxidative stress indicators such as superoxide dismutase (SOD), glutathione (GSH), and malondialdehyde (MDA) in liver tissue were measured. The changes of liver structure were observed under transmission electron microscopy. The apoptosis and reactive oxygen species (ROS) level in liver tissue were observed under fluorescence microscope. Western blotting was used to detect the protein expressions of nuclear factor E2-related factor 2 (Nrf2), hemeoxygenase-1 (HO-1), Kelch-like ECH-associated protein 1 (Keap1), and cleaved caspase-9 in liver tissue. Results:Compared with the Control group, the liver mitochondria in the DQ group showed severe swelling, partial dissolution of the matrix, and cristae rupture and loss; the levels of plasma AST and ALT significantly increased, the MDA content in the liver increased, the activities of SOD and GSH decreased, the level of ROS significantly increased, the number of apoptotic cells in the liver significantly increased, the protein expressions of Nrf2 and HO-1 significantly decreased, and the protein expressions of Keap1 and cleaved caspase-9 significantly increased. Compared with the DQ group, the mitochondrial damage in the DQ+SFN group was reduced, the levels of plasma AST and ALT were significantly reduced [ALT (U/L): 58.22±4.39 vs. 79.94±3.32, AST (U/L): 177.64±8.40 vs. 219.62±11.60, both P < 0.01], the liver MDA content decreased, and the activities of SOD and GSH increased [MDA (μmol/g: 5.63±0.18 vs. 5.96±0.29, SOD (kU/g): 102.05±4.01 vs. 84.34±5.34, GSH (mmol/g): 16.32±1.40 vs. 13.12±1.84, all P < 0.05], the production of ROS in liver tissue was significantly reduced [ROS (fluorescence intensity): 115.90±10.89 vs. 190.70±10.16, P < 0.05], and apoptotic cells were significantly reduced (cell apoptosis index: 4.39±1.00 vs. 10.71±0.56, P < 0.01), the protein expressions of Nrf2 and HO-1 were significantly increased, while the protein expressions of Keap1 and cleaved caspase-9 were significantly decreased (Nrf2/β-actin: 1.15±0.04 vs. 0.93±0.05, HO-1/β-actin: 1.75±0.12 vs. 0.78±0.04, Keap1/β-actin: 1.00±0.14 vs. 1.28±0.13, cleaved caspase-9/β-actin: 1.31±0.12 vs. 1.81±0.09, all P < 0.05). However, there was no statistically significant difference in various indicators between the SFN group and the Control group. Conclusion:SFN can activate the Keap1/Nrf2 signaling pathway to alleviate DQ induced acute liver injury in mice.

Objective To investigate the prevalence of tension-type headache(TTH)in children and adolescents aged 0-19 years globally in 1990-2021,and to provide a basis for the prevention and treatment of TTH.Methods Based on the Global Burden of Disease Study data,the age-standardized prevalence distribution of TTH and its changing trend were analyzed among the children and adolescents aged 0-19 years,with different sexes,age groups,sociodemographic index(SDI)regions and countries/territories.Results The age-standardized prevalence rate(ASPR)of TTH in children and adolescents aged 0-19 globally in 2021 was 17 339.89/100 000,which was increased by 1.73%since 1990.The ASPR in females was slightly higher than that in males(1990:17 707.65/100 000 vs 16 403.78/100 000;2021:17 946.29/100 000 vs 16 763.09/100 000).The ASPR in adolescence was significantly higher than that in school-aged and preschool periods(1990:27 672.04/100 000 vs 10 134.16/100 000;2021:28 239.04/100 000 vs 10 059.39/100 000).Regions with high SDI exhibited a higher ASPR than the other regions,with significant differences in prevalence rates across different countries.From 1990 to 2021,there was a slight increase in global ASPR,with an average annual percentage change(AAPC)of 0.06%.Females experienced a smaller increase than males based on AAPC(0.04%vs 0.07%).There was reduction in ASPR in preschool and school-aged groups,with an AAPC of-0.02%,while there was a significant increase in ASPR in adolescence,with an AAPC of 0.07%.ASPR decreased in regions with low-middle and low levels of SDI,with an AAPC of-0.02%and-0.04%,respectively,while it increased in regions with middle SDI,with an AAPC of 0.24%.Conclusions There is a consistent increase in the ASPR of TTH in children and adolescents aged 0-19 years globally,with significant differences across sexes,age groups,SDI regions and countries/territories.

Tubulin beta 4A class IVa (TUBB4A) spectrum disorders include autosomal dominant dystonia type 4 or hypomyelination with atrophy of the basal ganglia and cerebellum (H-ABC syndrome). However, in rare cases, only mild hypomyelination in the cortex with no basal ganglia atrophy may be observed. We report a case of a family with TUBB4A mutation and complicated hereditary spasticity paraplegia (HSP). We performed quadro whole-exome sequencing (WES) on the family to identify the causative gene of progressive spastic paraparesis with isolated hypomyelination leukodystrophy. We identified a novel TUBB4A p.F341L mutation, which was present in all three affected patients but absent in the unaffected father. The affected patients presented with adult-onset TUBB4A disorder, predominant spastic paraparesis with/without ataxia, and brain hypomyelination with no cognitive impairment or extrapyramidal symptoms. In the literature, HSP is considered a TUBB4A spectrum disorder.