Myocardial infarction (MI) is the leading cause of cardiovascular disease-related death worldwide. Nonetheless, existing therapeutic approaches for MI are hampered by issues such as reliance on pharmacological agents and suboptimal patient adherence. Caffeic acid (CA) is a bioactive polyphenolic compound with important anti-inflammatory, anti-bacterial and anti-oxidant functions. Still, its specific role and mechanism in treating cardiovascular disease remain to be further studied. In recent years, a large number of studies have shown that the kelch-like ECH-associated protein 1/nuclear factor erythroid 2 related factor 2 (Keap1/Nrf2) pathway is a key factor in the occurrence and development of cardiovascular diseases. In this study, H₂O₂-induced oxidative stress model of H9c2 cells and left anterior descending branch (LAD) conjunctival induced acute myocardial infarction reperfusion (AMI/R) model were used to evaluate the protective effect of CA on the heart. The interaction between CA and Keap1 was analyzed by CA-labeled fluorescence probe, target fishing, isothermal titration calorimetry (ITC), protein crystallography and surface plasmon resonance (SPR). Our results suggested that CA binds Keap1 and degrades Keap1 in a p62-dependent manner, further promoting nuclear transcription of Nrf2 and thus effectively reducing oxidative stress. In addition, based on the three-dimensional eutectic structure, it was confirmed that CA directly targets Keap1 protein by interacting with residues M550 and N532, inducing conformation changes in Keap1 protein. We also found that the CA analog chlorogenic acid (GCA) can bind Keap1. In conclusion, this study elucidates a novel molecular mechanism and structural basis for the protective effects of CA against oxidative damage via the Keap1-Nrf2 pathway.

Objective:To analyze the effect of joint management of type 2 diabetes mellitus (T2DM) between specialty and community under the model of National Diabetes Prevention and Control Center (DPCC).Methods:A total of 2 527 T2DM patients managed by DPCC Pingshan Center of Shenzhen from January 1, 2022 to December 31, 2024 were retrospectively included. After management, the rate of downturn, reexamination rate, blood pressure compliance rate, metabolic indicators (waist circumference, body mass index, fasting blood glucose, glycosylated hemoglobin, blood lipids) and screening rate of chronic complications of diabetes (atherosclerotic cardiovascular disease, microvascular disease, diabetic peripheral neuropathy) were analyzed. Those included 2022 ( n=564), 2023 ( n=1 477), and 2024 ( n=2 527). Results:The downturn rate in 2022, 2023 and 2024 increased year by year (22.8% vs 67.2% vs 89.9%, P<0.01), and the review rate (41.1% vs 62.2% vs 52.7%, P<0.01), complication screening rate (51.6% vs 85.3% vs 62.2%, P<0.01), blood pressure compliance rate (53.1% vs 78.0% vs 67.2%, P<0.01), body mass index compliance rate (13.2% vs 17.3% vs 28.6%, P<0.01), fasting blood glucose meeting rate (46.4% vs 60.2% vs 68.5%, P<0.01), glycated hemoglobin meeting rate (58.4% vs 63.2% vs 45.6%, P<0.01) were relatively improved. Waist circumference compliance rate (30.6% vs 27.7% vs 21.6%) and blood lipid compliance rate (33.6% vs 35.5% vs 31.9%) were not significantly improved, and the review rate, blood pressure compliance rate and complication screening rate in 2024 were lower than those in 2023 and higher than those in 2022. Conclusions:The combined management of type 2 diabetes under the DPCC model has significant effects on improving the down-conversion rate, rediagnosis rate, blood pressure compliance rate, metabolic index compliance rate and the screening rate of diabetes-related chronic complications in patients with diabetes. At the same time, it was also found that with the progress of hierarchical diagnosis and treatment, the review rate, complication screening rate, blood pressure, waist circumference, blood lipid and glycosylated hemoglobin reached the standard of patients decreased compared with the previous situation, which needs to be further analyzed and improved.

Objective:To analyze the effect of joint management of type 2 diabetes mellitus (T2DM) between specialty and community under the model of National Diabetes Prevention and Control Center (DPCC).Methods:A total of 2 527 T2DM patients managed by DPCC Pingshan Center of Shenzhen from January 1, 2022 to December 31, 2024 were retrospectively included. After management, the rate of downturn, reexamination rate, blood pressure compliance rate, metabolic indicators (waist circumference, body mass index, fasting blood glucose, glycosylated hemoglobin, blood lipids) and screening rate of chronic complications of diabetes (atherosclerotic cardiovascular disease, microvascular disease, diabetic peripheral neuropathy) were analyzed. Those included 2022 ( n=564), 2023 ( n=1 477), and 2024 ( n=2 527). Results:The downturn rate in 2022, 2023 and 2024 increased year by year (22.8% vs 67.2% vs 89.9%, P<0.01), and the review rate (41.1% vs 62.2% vs 52.7%, P<0.01), complication screening rate (51.6% vs 85.3% vs 62.2%, P<0.01), blood pressure compliance rate (53.1% vs 78.0% vs 67.2%, P<0.01), body mass index compliance rate (13.2% vs 17.3% vs 28.6%, P<0.01), fasting blood glucose meeting rate (46.4% vs 60.2% vs 68.5%, P<0.01), glycated hemoglobin meeting rate (58.4% vs 63.2% vs 45.6%, P<0.01) were relatively improved. Waist circumference compliance rate (30.6% vs 27.7% vs 21.6%) and blood lipid compliance rate (33.6% vs 35.5% vs 31.9%) were not significantly improved, and the review rate, blood pressure compliance rate and complication screening rate in 2024 were lower than those in 2023 and higher than those in 2022. Conclusions:The combined management of type 2 diabetes under the DPCC model has significant effects on improving the down-conversion rate, rediagnosis rate, blood pressure compliance rate, metabolic index compliance rate and the screening rate of diabetes-related chronic complications in patients with diabetes. At the same time, it was also found that with the progress of hierarchical diagnosis and treatment, the review rate, complication screening rate, blood pressure, waist circumference, blood lipid and glycosylated hemoglobin reached the standard of patients decreased compared with the previous situation, which needs to be further analyzed and improved.

Objective:To investigate the changes of T lymphocyte subsets in peripheral blood of patients with diffuse large B-cell lymphoma (DLBCL) and its clinical significance.Methods:The clinical data of 99 DLBCL patients admitted to the First Affiliated Hospital of Xiamen University from January 2022 to January 2023 were retrospectively analyzed. T lymphocyte subsets in peripheral blood before and after treatment were detected by using flow cytometry. According to the disease status at the time of blood collection and detection, the patients were divided into the newly-diagnosed DLBCL group (28 cases), and the newly-treated remission DLBCL group (71 cases); and 40 healthy volunteers undergoing the physical examination during the same period were selected as the healthy control group. The proportion and absolute count differences of T lymphocytes and the related subsets in 3 groups were compared. Besides, the correlation among T lymphocyte subsets, the correlation of each subset with international prognostic index (IPI) score and treatment response in newly-diagnosed DLBCL patients were further analyzed.Results:The proportion of CD3 + T cells in newly-diagnosed DLBCL group was decreased compared with that in the healthy control group [(58±14)% vs. (67±7)%, P < 0.05]. The absolute count of CD3 + T cells in both newly-diagnosed group and the newly-treated remission group was reduced compared with that in the healthy control group [(875±483) /μl and (808±553) /μl vs. (1 374±279) /μl, P < 0.001]. The absolute count of CD4 + and CD8 + T cells in newly-diagnosed group was decreased compared with that in the healthy control group [(478±313) /μl vs. (695±154) /μl, (316±181) /μl vs. (525±193) /μl, all P < 0.001]. Both the proportion and absolute count of CD4 + T cells in the newly-treated remission DLBCL group were decreased compared with those in the newly-diagnosed DLBCL group and the healthy control group [(40±14)% vs. (53±14)% and (51±9)%, (313±247) /μl vs. (478±313) /μl and (695±154) /μl, all P < 0.05]. The porportion of CD8 + T cells was increased compared with that in the other two groups [(51±15)% vs. (37±12)% and (38±9)%, all P < 0.001]. Compared with the healthy control group, the effect/memory subsets proportion of regulatory T cell (Treg) and conventional T cell (Tcon) were increased in both newly-diagnosed DLBCL group and the newly-treated remission DLBCL group [(79±16)% and (84±12)% vs. (71±11)%,(72±16)% and (76±14)% vs. (62±13)%, all P < 0.05], and the proportion of CD127 + memory Tcon and CD8 + T cell subsets was reduced [(73±14)% and (66±20)% vs. (85±8)%,(39±15)% and (25±21)% vs. (62±16)%, all P < 0.05]. In newly-diagnosed DLBCL group, the absolute counts of CD3 + T and CD4 + T cells were negatively correlated with the proportion of effector Treg ( r = -0.379, P = 0.049; r = -0.384, P = 0.040, respectively). IPI score of DLBCL patients was correlated with the proportion of CD8 + T cells ( Eta2 = 0.15, P = 0.038). The proportion of CD127 + memory Tcon in patients with non-complete remission was increased compared with that in patients with complete remission after treatment ( P = 0.020). Conclusions:The proportion and absolute count of T lymphocyte cells in peripheral blood of newly-diagnosed DLBCL patients is decreased, and the differentiation state of T lymphocyte cells shows change trend, which is related to the clinical characteristics and treatment response of DLBCL patients. Even if DLBCL patients have achieved treatment remission, T lymphocyte cells are not completely return to the normal.

A 47-year-old female patient with Helicobacter pylori (HP) infection received anti-HP regimen, including pantoprazole enteric coated tablets 40 mg orally twice daily, amoxicillin capsules 1 g orally twice daily, and furazolidone tablets 0.1 g orally thrice daily. The patient had previously taken amoxicillin capsules and pantoprazole enteric coated tablets several times without adverse reactions. On the 12th day after receiving anti-HP treatment, the patient developed fever, shortness of breath, body temperature of 38.3 ℃, and conjunctival hemorrhage of the right eyeball. Laboratory tests showed that percentage of eosinophils was 0.08. Chest CT showed interstitial pulmonary edema in bilateral lungs and a small amount of effusion in the right pleural cavity. Acute lung injury associated with furazolidone was considered. Furazolidone was stopped. The patient received glucocorticoid and symptomatic treatments. Six days later, the patient′s symptoms such as fever and shortness of breath were relieved and the conjunctival hemorrhage in the right eye was absorbed; laboratory test showed that percentage of eosinophils was 0.008; the chest CT showed that the interstitial pulmonary edema in bilateral lungs was more absorbed than before and the pleural effusion on the right side was basically absorbed.

A 47-year-old female patient with Helicobacter pylori (HP) infection received anti-HP regimen, including pantoprazole enteric coated tablets 40 mg orally twice daily, amoxicillin capsules 1 g orally twice daily, and furazolidone tablets 0.1 g orally thrice daily. The patient had previously taken amoxicillin capsules and pantoprazole enteric coated tablets several times without adverse reactions. On the 12th day after receiving anti-HP treatment, the patient developed fever, shortness of breath, body temperature of 38.3 ℃, and conjunctival hemorrhage of the right eyeball. Laboratory tests showed that percentage of eosinophils was 0.08. Chest CT showed interstitial pulmonary edema in bilateral lungs and a small amount of effusion in the right pleural cavity. Acute lung injury associated with furazolidone was considered. Furazolidone was stopped. The patient received glucocorticoid and symptomatic treatments. Six days later, the patient′s symptoms such as fever and shortness of breath were relieved and the conjunctival hemorrhage in the right eye was absorbed; laboratory test showed that percentage of eosinophils was 0.008; the chest CT showed that the interstitial pulmonary edema in bilateral lungs was more absorbed than before and the pleural effusion on the right side was basically absorbed.

Objective:To assess the age-related differences in the management strategies and outcomes of patients with acute coronary syndrome (ACS) under the chest pain center model.Methods:Clinical data of 2 833 patients with ACS were enrolled in the retrospective observational registry between January 2017 and June 2019 at 11 hospitals with chest pain centers in Chengdu. The patients were divided into four groups according to their ages: < 55 years old group ( n = 569), 55-64 years old group ( n = 556), 65-74 years old group ( n = 804), ≥ 75 years old group ( n = 904). The collected data included the patients' demographic characteristics, cardiovascular risk factors, medical history, symptoms and signs of onset, experimental examination, types of ACS and the time from the symptom to the hospital (S-to-D), etc., and the clinical characteristics, management strategies, all-cause mortality in the hospital, and the incidence of major adverse cardiovascular and cerebrovascular events (MACCE) within 1 year after discharge were compared. The primary end point was the clinical outcome of ACS patients in different age groups, including all-cause deaths in the hospital and the incidence of MACCE within 1 year after discharge. The secondary end point was the proportion of ACS patients underwent percutaneous coronary intervention (PCI) in different age groups. Multivariate Logistic regression was used to analyze the risk factors of all-cause deaths in ACS patients. Kaplan-Meier curve was used to express the incidence of MACCE within 1 year after discharge in different age groups. Multivariate Cox regression was used to analyze the factors affecting the incidence of MACCE within 1 year after discharge of ACS patients. Results:As age increased, the proportion of male patients gradually decreased, and the percentages of male patients aged < 55 years old, 55-64 years old, 65-74 years old, and ≥ 75 years old were 87.2% (496/569), 77.0% (428/556), 66.4% (534/804), and 60.1% (543/904), respectively; and ACS patients combined with hypertension, diabetes, coronary heart disease, and stroke history were more common [the percentages of patients with hypertension aged < 55 years old, 55-64 years old, 65-74 years old, ≥ 75 years old were 41.3% (235/569), 52.2% (290/556), 59.7% (480/804), and 66.9% (605/904); the percentages of diabetes were 18.6% (106/569), 25.5% (142/556), 27.0% (217/804), and 28.2% (255/904); the percentages of coronary heart disease were 10.1% (57/564), 13.9% (77/555), 17.6% (141/803), and 23.7% (213/899); the percentages of stroke were 0.7% (4/564), 4.0% (22/552), 4.5% (36/801), and 8.6% (77/894)]. But the percentages of patients with a history of active smoking, typical chest pain/chest tightness and dyslipidemia were significantly reduced [the percentages of smoking history were 60.2% (340/565), 48.0% (266/554), 33.7% (270/801), and 21.7% (195/899), typical chest pain/chest tightness were 96.9% (536/553), 96.4% (516/535), 91.8% (716/780), 90.2% (776/860); the percentages of dyslipidemia were 11.2% (63/565), 9.2% (51/553), 5.7% (46/802), and 4.9% (44/896)], the time of S-to-D was significantly prolonged [minutes: 176.0 (73.5, 557.0), 194.5 (89.3, 682.3), 221.0 (98.8, 940.5), and 270.0 (115.0, 867.0)], hemoglobin (Hb) level was significantly reduced(g/L: 145.44±17.43, 135.95±19.25, 129.75±19.03, 122.19±20.55), and the incidence of non-ST-segment elevation myocardial infarction (NSTEMI) increased significantly [18.6% (106/569), 20.5% (114/556), 26.6% (214/804), 26.5% (240/904)], and the differences were statistically significant (all P < 0.05). The proportion of Killip grade Ⅲ -Ⅳ were the highest in patients aged ≥ 75 years old, 9.0% and 12.6%, respectively. Compared with the groups aged < 55 years old, 55-64 years old, and 65-74 years old, the proportion of patients aged ≥ 75 years old who underwent PCI was the lowest, and the all-cause mortality in the hospital and the incidence of 1-year MACCE of patients underwent PCI were significantly lower than those of patients underwent conservative treatment [6.0% (28/463) vs. 10.4% (45/434), 14.6% (43/294) vs. 24.3 % (55/226), both P < 0.05]. As age increased, the hospital all-cause mortality and the 1-year MACCE incidence increased (all-cause mortality rates in < 55 years old, 55-64 years old, 65-74 years old, ≥ 75 years old groups were 0.9%, 2.2%, 5.5%, 8.3%, and the 1-year MACCE incidences were 5.0%, 6.7%, 13.9%, 18.7%, both P < 0.01). The multivariate Logistic regression analysis showed that age, cardiogenic shock, ST-segment elevation myocardial infarction (STEMI), the number of vascular disease and underwent PCI were the independent risk factors of all-cause mortality [the odds ratio ( OR) and 95% confidence interval (95% CI) were 1.644 (1.356-1.993), 11.794 (7.469-18.621), 2.449 (1.419-4.227), 1.334 (1.096-1.624), 0.391 (0.247-0.619), all P < 0.001]. Cox regression analysis showed that age, STEMI, the number of vascular disease and underwent PCI were independent risk factors of the occurrence of MACCE within 1 year after discharge [hazard ratio ( HR) and 95% CI were 1.354 (1.205-1.521), 1.387 (1.003-1.916), 1.314 (1.155-1.495), 0.547 (0.402-0.745), all P < 0.05]. Conclusions:In the chest pain center model, compared with other age of ACS patients, the proportion of NSTEMI in elderly patients group aged ≥ 75 years old was higher, the proportion of PCI was lower, and the clinical outcome was worse. However, the prognosis of elderly patients receiving PCI treatment was better than the patients receiving conservative treatment.

Objective:To investigate the safety and therapeutic effect of Shakubatrivalsartan in the treatment of pediatric dilated cardiomyopathy.Methods:Clinical information, treatment and prognosis of 5 cases with dilated cardiomyopathy in the First Affiliated Hospital of Xinxiang Medical University from June 2018 to December 2020 were retrospectively analyzed, and relevant literatures were reviewed.Results:A total of 5 cases of children with dilated cardiomyopathy were analyzed, including 3 males and 2 females with age of 12-17 years.Their median left ventricular ejection fraction (LVEF), left ventricular end diastolic dimension (LVDd), N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels were 37% (20%-41%), 61 mm (59-67 mm), and 13 250 ng/L (12 310-21 823 ng/L), respectively.The median conventional treatment time was 5 months (1-12 months), in which, the condition of heart failure gradually progressed, and the median LVEF, LVDd and NT-proBNP levels were reduced to 33% (19%-37%), 61 mm (60-74 mm), 13 144 ng/L (8 086-15 137 ng/L). After less than 3 months of follow-up following conventional treatment plus Shakubatrivalsartan, NT-proBNP level significantly decreased in 5 cases.Besides, 4 cases had improved cardiac function, and the other one′s improvement was not obvious.The blood pressure of 5 cases decreased at varying degrees after medication of Shakubatrivalsartan, which should be closely monitored during drug titration.No adverse reactions were reported.Conclusions:Shakubatrivalsartan for the treatment of pediatric dilated cardiomyopathy is safe and effective, which can alleviate or reverse the process of myocardial remodeling and improve cardiac ejection fraction, thus improving the prognosis.

Objective To assess the efficacy and safety of 100 mg or 200 mg yimitasvir phosphate combined with sofosbuvir in patients with non-cirrhotic chronic hepatitis C virus ( HCV) genotype 1 infection who were treatment-na?ve or had a virologic failure to prior interferon-based treatment.Methods A multicenter, randomized, open-label, phase 2 clinical trial was conducted.The patients were randomly assigned to yimitasvir phosphate 100 mg+sofosbuvir 400 mg group (Group 100 mg) and yimitasvir phosphate 200 mg+sofosbuvir 400 mg group ( Group 200 mg) in a 1∶1 ratio with the stratified factors of " treatment-naive" or"treatment-experienced" for 12 weeks and followed up for 24 weeks after the end of treatment.During the clinical trial, HCV RNA was tested in all patients.Resistance of virus in patients who didn′t achieved sustained virological response (SVR) was monitored.Safety and tolerability were assessed by monitoring adverse events , physical examination , laboratory examination, electrocardiogram, and vital signs during the study.The primary end point was SVR12 after the end of therapy.Descriptive statistics were used for categorical variables and eight descriptive statistics were used for continuous variables.Descriptive statistics were used and summarized according to HCV genotypes and treatment groups.Safety data were presented using descriptive statistics and summarized according to treatment groups.Results A total of 174 subjects were screened from July 31, 2017 to September 26, 2018.One hundred and twenty-nine patients were successfully enrolled and received treatment , and 127 completed the study.There were 64 patients and 65 patients assigned to Group 100 mg and Group 200 mg, respectively.Among the 129 patients who underwent randomization and were treated , 18.6% were treatment-experienced and: 100%were HCV genotype 1b infection.The total SVR rate was 98.4%(127／129), with 98.4%(63／64, 95%confidence interval [CI]: 91.60%-99.96%) in the Group 100 mg, and 98.50%(64／65, 95%CI: 91.72%-99.96%) in the Group 200 mg.There was no significant difference between the two groups (χ2 ＝0.000 2, P＝0.989 2).The SVR rates in treatment-naive group and treatment-experienced group were 98.10%(95%CI: 93.29%-99.77%) and 100.00%(24／24, 95%CI: 85.75%-100.00%), respectively.Virological failure during treatment ( including breakthrough , rebound and poor efficacy) and relapse after treatment did not occur during the trial.By Sanger sequencing , 11.6%(15／129) patients had baseline NS5A Y93H／Y or Y93H resistance-associated substitutions ( RAS), 1.6%( 2／129) patients had baseline NS5A L31M RAS.No mutation was observed in NS5B S282 at baseline.There was no S282 mutation in HCV NS5B.A total of 100 (77.5%) subjects had adverse events.No adverse events ≥Grade 3 or severe adverse events related to the study treatment.No patient prematurely discontinued study treatment owing to an adverse event.No life-threatening adverse event was reported.Conclusion Twelve weeks of yimitasvir phosphate 100 mg or 200 mg combined with sofosbuvir 400 mg daily is a highly effective and safe regimen for patients without cirrhosis with HCV genotype 1b infection who had not been treated previously or had a virologic failure to prior interferon-based treatment.

Objective: To evaluate the safety and efficacy of ombitasvir/paritaprevir/ritonavir (OBV/PTV/r) 25/150/100 mg once daily combined with dasabuvir 250mg, twice daily in non-cirrhotic Chinese adult patients with newly diagnosed and treated chronic HCV genotype 1b infection. Methods: A randomized, double-blind, placebo-controlled, multicenter phase 3 clinical trial was conducted in mainland China, Korea, and Taiwan.Safety and efficacy of OBV/PTV/r plus DSV administered for 12 weeks were evaluated in a newly diagnosed and treated (interferon alpha /pegylated interferon alpha) and ribavirin non-cirrhotic adults with chronic HCVgenotype 1b infection. Patients randomly received OBV/PTV/r plus DSV for 12 weeks (Group A), or placebo for 12 weeks (Group B) followed by an open-label phase of OBV/PTV/r plus DSV for 12 weeks. Sustained response (SVR12) rate obtained at 12 weeks and (SVR24) 24 weeks after discontinuation of treatment, and the incidence of adverse events and laboratory abnormalities after double-blind and open-label phase treatment were assessed. Results: A total of 410 cases of Chinese patients were included and randomly assigned to group A and B (with 205 cases in each group) in a 1:1 ratio. The rates of SVR12 and SVR24 were 99% (95% CI: 94.8% - 99.8%) in the newly diagnosed patients in group A (205 patients) and the rates of SVR12 and SVR24 were 100% in treated patients (95% CI: 96.3% - 100%). Different baseline characteristics had no effect on SVR12 and SVR24 rates. Most of the adverse events occurred were mild, asymptomatic, and≥ 3 laboratory abnormalities during treatment were rare, including elevation of alanine aminotransferase (2 cases in double-blind stage A group), aspartate aminotransferase (Double-blind stage A (3 cases) and total bilirubin (1 case in open-label phase B group); however, those mild adverse events could be recovered after drug withdrawal or discontinuation. only1 person discontinued drugs due to adverse events (Group B, open-label phase). Conclusion The 12 weeks treatment course of OBV/PTV/r combined with DSV produced 99% ~ 100% rates of SVR12 and SVR24 in non-cirrhotic Asian adult patients with newly diagnosed and treated chronic HCV genotype 1b infection, and the tolerance and safety were good.