Objective To explore the effect of antinuclear antibody ( ANA+dsDNA),extractable nuclear antigen (ENA) and antineutrophil cytoplasmic antibody (ANCA) on the clinical manifestation and cerebrospinal fluid characteristics of neuromyelitis optica (NMO).Methods All 41 patients with NMO in PUMC hospital from 1985 to 2009 were retrospectively reviewed.All patients underwent examination of serum ANA+dsDNA,ENA and ANCA.Fourteen positive-autoantibody patients were compared with 27negative-autoantibody patients in gender,onset age,duration,relapse ratio,first demyelination event,the extent of optic neuritis and myelitis,EDSS,CSF protein,WBC,Oligoclonal band, 24 hours IgG index and myelin basic protein.Results The 14 NMO patients (34.1%) had positive non-organ-specific antibodies.NMO patients who had negative autoantibodies were compared with NMO patients with positive autoantibodies with significantly higher EDSS (the EDSS score were 4.5 and 2.5 respectively,U=92.5,P=0.008),more complete damage of spinal cord (3/14 vs 0/27, x2=6.736, P=0.0095) and tended to have higher visual Function Scale in remitting phase.There was no significant difference on the gender,onset age,duration,relapse ratio,first demyelination event.The positive-autoantibody patients had higher CSF WBC (2.0 vs 0,U=68.0,P=0.007) and tended to have lower 24 hours IgG index (-8.663 vs 0.163,U=30.0,P=0.053).There was no significant difference in CSF protein,MBP and OB.Conclusion NMO patients with positive autoantibodies have more severe intrathecal autoimmune inflammatory and disability,so they might need more intensive treatment.

Objective To explore the neuroprotection of Pabing Formula I Granules for Parkinson's disease (PD) rats. Methods PD rats were induced with injection of 6-hydroxy dopamine twice stereotaxically into the left striatum. 40 rats modeled successfully were divided into model group (n=12), high dose group (n=14) and low dose group (n=14), and the other 8 rats were as normal group. The high dose group and low dose group received Pabing Formula I Granules 18 g/kg and 9 g/kg respectively, while the model group and normal group were given distilled water at the same volume, once a day for 32 d. Then, they were assessed with rotation test. The activities of superoxide dismutase (SOD), the levels of glutathione (GSH) and malonaldehyde (MDA) of their left striatum were measured, and the expression of P-Akt (ser 473), Bcl-2, and Bax in substantia nigra were detected with immunohistochemistry. Results The rotation released was significant different among the model, high dose and the low dose groups after treatment (P<0.01), with the activities of SOD (P<0.01) and the content of GSH (P<0.01) increasing and the content of MDA (P<0.01) descreasing. There was significant difference in the content of GSH (P<0.01) and MDA (P<0.01) between the high and the low dose groups. There was significant difference in expression of P-Akt (ser 473), Bcl-2 and Bax among the model, high dose and the low dose groups, as well as the Bcl-2/Bad ratio (P<0.05). Conclusion Pabing Formula I Granules plays neuroprotective effect through enhancing antioxidation and eliminating free radicals ability and Akt signaling pathway, which appears as dose-effect relationship.

Objective To explore cardioprotective effect of matrine on myocardial ischemia in hypercholesterolemia rats. Methods Myocardial infarction was induced by subcutaneous injection of isopreterenol (ISO, 85 mg/kg) once daily for two consecutive days in rats feeding cholesterol-rich diet for 4 weeks. Content of serum lipid, myocardial injury marker enzymes, lipid peroxidatase and activities of antioxidative enzymes in serum and/or heart tissues were measured, and cardiac function was evaluated. Results Administration of matrine (50, 100, and 200 mg/kg, respectively) decreased serum level of TC and TG, improved left ventricle (LV) contractile function (increased LVSP and +dp/dtmax) and LV diastolic function (decreased LVEDP and increased -dp/dtmax), depressed the levels of myocardial injury marker enzymes of lactic dehydrogenase (LDH) and creatine kinase (CK), promoted the activities of antioxidative enzymes of superoxide dismutase (SOD), catalyst (CAT), and glutathione peroxidase (GHS-PX), as well as decreased the content of lipid peroxidation product of malondialdehyde (MDA) in plasma and/or myocardial tissues in hypercholesterolemia rats with myocardial infarction. Histopathology examination demonstrated that matrine could attenuate ISO-induced myocardial infarction morphologically in hypercholesterolemia rats. Conclusion Our results suggest that cardioprotective effect of matrine on myocardial infarction in hypercholesterolemia rats is attributed to its ability to decrease the TC and TG content of serum, enhance the activities of antioxidative enzymes, and maintain the stability of myocardial cellular membranes.

AIM: To study the effect of ligustrazine on the cardiacmyocyte lesion in rats with type 2 diabetes mellitus.METHODS: Male Wistar rats were injected with STZ via tail vein under high-glucose and high-fat feeding for 4 weeks to establish the animal model of type 2 diabetes mellitus.Ligustrazine at different doses was used to treat the diabetic rats.The body weight, blood glucose and the morphology of heart tissues were observed.The myocardial levels of IL-1β, IL-6 and TNF-α were detected by ELISA, and the protein expression of IKKβ and NF-κB in the myocardium was determined by Westeren blotting.RESULTS: Ligustrazine at high dose alleviated the body weight reduction and blood glucose elevation cause by diabetes, and reduced pro-inflammatory factors IL-1β, TNF-α and IL-6.Moreover, the protein expression of IKKβ and NF-κB was significant decreased by ligustrazine.CONCLUSION: Ligustrazine inhibits the myocardial inflammation caused by diabetes through anti-inflammatory pathway.

Histone deacetylase 1 ( sirtuin 1, SIRT1) is an important member of deacetylase family, and plays an important role in the process of malignant tumor and embryonic development. In this article it was found that overexpression of SIRT1 could accelerate the DNA synthesis in human pancreatic beta cell CRL-1837 and inhibit cell senescence. SIRT1 also could bind to p53 as detected by co-immunoprecipitation and could change the phosphorylation level of p53.

OBJECTIVE:To establish the method for the content determination of rapamycin (RAPA) in human monocyte THP-1 derived foam cells,and to study the effects of RAPA targeting preparation(RAPA-NP-Apt)targeting at foam cells. METH-ODS:Foam cells model were established through THP-1 cells were induced by oxidized low density lipoprotein. Foam cells were incubated with 200 ng/mL RAPA or 200,400,800 ng/mL RAPA-NP-Apt for 60 min. The content of RAPA was determined by HPLC. The determination was performed on Diamonsil C18 column with mobile phase consisted of acetonitrile-water(90:10,V/V) at flow rate of 1.0 mL/min. The column temperature was set at 40 ℃,and the detection wavelength was 278 nm. The sample size was 20 μL. RESULTS:The concentration of RAPA ranged 50-6400 ng/mL (r=0.99996) with average recovery of 98.72%(RSD=0.62%,n=3). RSDs of inter-day and intra-day were not more than 6.15%(n=6),RSD of stability was lower than 2%(n=6),and RSD of repeatability was 1.64%(n=6). After foam cells were incubated with RAPA or low-concentration,medi-um-concentration and high-concentration of RAPA-NP-Apt,the contents of RAPA were 12,43,98,140 ng/106 cells. CONCLU-SIONS:The method is simple,stable and reproducible. It can be used for content determination of RAPA in foam cells. RA-PA-NP-Apt can improve the effects of RAPA targeting at foam cells.

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 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.

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 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.