OBJECTIVES: Injury to human cardiac microvascular endothelial cells (HCMECs) compromises myocardial microcirculation and may contribute to major cardiovascular events such as coronary heart disease, posing a serious health threat. Understanding the mechanisms of hypoxia-induced HCMEC damage is thus of great clinical relevance. This study aims to investigate the protective effects and underlying mechanisms of Li Qi Huo Xue Di Wan against hypoxia-induced HCMEC injury. METHODS: HCMECs were cultured under hypoxic conditions for 24 hours to establish a cellular model of hypoxic injury. Cells were divided into six groups: normal control, hypoxia, hypoxia + low-dose Li Qi Huo Xue Di Wan, hypoxia + medium-dose, hypoxia + high-dose, and hypoxia + salvianolic acid B (positive control). Cell viability was assessed using the MTS assay. Lactate dehydrogenase (LDH) release and malondialdehyde (MDA) content were measured to evaluate cytotoxicity and oxidative stress. Activities of superoxide dismutase (SOD), catalase (CAT), caspase-3, and caspase-8 were determined with corresponding assay kits. Apoptosis was analyzed by flow cytometry, and expression of necroptosis-related proteins, receptor-interacting protein kinase 1 (RIPK1) and its phosphorylated form (p-RIPK1), receptor-interacting protein kinase 3 (RIPK3) and its phosphorylated form (p-RIPK3), mixed lineage kinase domain-like protein (MLKL) and its phosphorylated form (p-MLKL), was examined via Western blotting. RESULTS: Compared with the control group, hypoxia significantly decreased cell viability (P<0.01), increased MDA levels (P<0.05), and reduced CAT and SOD activity (P<0.05), accompanied by elevated apoptosis (P<0.01) and increased levels of p-RIPK1, p-RIPK3, and p-MLKL (P<0.05). High-dose Li Qi Huo Xue Di Wan significantly improved cell viability (P<0.01), reduced MDA content (P<0.05), increased CAT activity (P<0.05), and suppressed necroptosis-related protein expression (P<0.05) compared with the hypoxia group. CONCLUSIONS Li Qi Huo Xue Di Wan exerts a protective effect against hypoxia-induced injury in HCMECs. This effect is mediated by attenuation of oxidative stress, thereby reducing both apoptosis and necroptosis.
Humans ; Apoptosis/drug effects* ; Necroptosis/drug effects* ; Drugs, Chinese Herbal/pharmacology* ; Cell Hypoxia/drug effects* ; Endothelial Cells/pathology* ; Oxidative Stress/drug effects* ; Cells, Cultured ; Cell Survival/drug effects* ; Receptor-Interacting Protein Serine-Threonine Kinases/metabolism*

Objective:To observe the safety of 2-port non-vitrectomized subretinal injection (SRI) for the treatment of Bietti crystalline dystrophy (BCD).Methods:A exploratory clinical study. From February to May 2023, 6 BCD patients with 6 eyes who were confirmed by examination in Xiamen Eye Center of Xiamen University and were treated with SRI adeno-associated virus vector transgenic drugs were included in the study. Among them, 2 males had 2 eyes and 4 females had 4 eyes. Age were 34-60 years old. The study eye underwent adeno associated virus gene therapy via 2-port non-vitrectomized SRI. Two scleral ports were created using 25G vitrectomy trocar to place the light pipe and injection cannula. Anterior chamber paracentesis was performed to lower intraocular pressure. Under the silicone oil infusion mode of the vitrectomy machine, a 38G injection cannula penetrated the retina to reach the subretinal space. The injection speed was controlled by the foot pedal of the vitrectomy machine, and the drug was slowly injected into the subretinal space to create a subretinal bleb. if intra-ocular pressure assessed by finger palpation was high at the end of injection, drainage of the aqueous humor can be made by compressing the cornea incision until the intraocular pressure was normal. Patients were followed for 9-12 months and be examined using the same equipment and methods as before.Results:Retinal pigment epithelium and choroidal atrophy were observed in all 6 eyes of 6 patients were graded as stage Ⅲ by the fundus examination revealing atrophy of retinal pigmented epithelium and choroid, with or without yellow- white crystals and/or complex lipid. The range were operation time 9-14 minutes. No vitreous prolapse, retinal hemorrhage, or retinal tear was observed during surgery. After 24 hours, optical coherence tomogrophy examination showed absorption of subretinal fluid and retinal reattachment. None of the six patients showed corneal keratic precipitates, anterior chamber cells, vitreous cells, inflammation, high intraocular pressure, or retinal tear within the 9-month follow-up.Conclusion:Subretinal injection without vitrectomy using two ports is a safe and feasible alternative for adult gene therapy, and it shortens the surgical time.

Copper is a trace element essential for the maintenance of normal physiological functions in cardiovascular system,and its transport and metabolisms are regulated by various copper proteins such as copper-based enzymes,copper chaperones and copper transporters.The disturbance of copper level or abnormal expression of copper proteins are closely associated with the development of cardiovascular diseases such as atherosclerosis,hypertension,ischemic heart disease,myocardial hypertrophy and heart failure.Thus,intervention of copper ion signaling pathways is expected to be an effective measure for treating cardiovascular diseases.Some copper complexes,such as trientine,copper-aspirinate complex and copper(Ⅱ)diethyldithiocarbamate,have been found to play a role in the prevention and treatment of cardiovascular diseases and possess potential prospects.Exploring the role of copper in maintaining normal cardiovascular status and the potential application of copper complexes in the treatment of cardiovascular diseases may lay a foundation for finding new targets for prevention and treatment of various cardiovascular diseases,and provide new ideas for clinical treatment of cardiovascular diseases.

Objective: To evaluate the clinical effects of vitrectomy with or without fovea-sparing internal limiting membrane peeling on macular foveoschisis (MF) secondary to pathologic myopia. Methods: A non-randomized controlled study was adopted.Twenty-three patients (25 eyes) with refractive error ≥-8.00 DS and MF either combined with foveal retinal detachment or epi-macualr membrane or lamellar macular hole.The subjects were divided into non-internal limiting membrane peeling group (11 patients /11 eyes) who underwent triamcinolone (TA) assisted vitrectomy and fovea-sparing internal limiting membrane peeling group (12 patients/14 eyes) who underwent TA assisted vitrectomy with fovea-sparing internal limiting membrane peeling.The baseline data such as age, best corrected visual acuity (BCVA), refractive error, axial length were not significant difference between the two group.Main outcomes were BCVA, remission of MF defined by optical coherence tomographyc OCT as well as complications.This study followed the Declaration of Helsinki and this protocol was approved by Ethic Committee of Xiamen Eye Center of Xiamen University (NO.XMYKZX-2016-YWS-007). Results: All patients completed follow-up for more 6 months.BCVA (LogMAR) was 0.47±0.30 in non-internal limiting membrane peeling group and 0.40±0.33 in fovea-sparing internal limiting membrane peeling group, showing no significant difference between the two groups (t=0.66, P=0.52). Complete remission of MF was achieved in 22 eyes.The remission time in non-internal limiting membrane peeling group was 2.5 (1.8, 9.3) months, and 1.0 (1.0, 3.8) months in fovea-sparing internal limiting membrane peeling group, no statistical significance was obtained between the two groups (U=35.00, P=0.09). One eye had post-operative macular hole in non-internal limiting membrane peeling group, accounting for 9%, while in fovea-sparing internal limiting membrane peeling group, one eye had macular hole, accounting for 7%, and one eye had rhegmatogenous retinal detachment post-operatively, accounting for 7%. Conclusions MF can be resolved by vitrectomy while complete remission can achieved more quickly when combined with fovea-sparing internal limiting membrane peeling.

Objective: To observe the clinical efficacy of digital 3D heads-up display viewing system(3D viewing system) and intraoperative OCT (iOCT) in vitrectomy for myopic foveoschisis (MF). Methods: A retrospective, consecutive case series. From October 2018 to May 2019, Nineteen eyes of 19 consecutive patients with MF diagnosed in Xiamen Eye Center of Xiamen University who underwent vitrectomy were included in this study. There were 7 males and 12 females, with the mean age of 54.47±11.38 years. The average axial length was 30.40±2.30 mm, the mean logMAR BCVA was 0.56±0.31, the mean central foveal thickness (CFT) was 317.80±151.9.32 μm, the mean max retinal thickness (maxRT) was 556.7±143.7 μm. All the surgeries performed combined with 3D viewing system with iOCT. The standard 25G pars planar vitrectomy were performed with removing the posterior vitreous and indocyanine green (ICG) staining of internal limiting membrane (ILM) and air-fluid exchange. Thirteen of 19 eyes underwent fovea-sparing ILM peeling and the other 6 eyes not. The average follow-up was 4.2±1.4 months. All the patients were on regular follow-up to document the changes on BCVA, anatomical changes in macula, CFT and maxRT. Paired t test was used to compare BCVA, CFT and maxRT before and after surgery. Results: The fine images of macula were clearly shown on the 3D viewing system in all eyes. The electronic green filter enhanced the contrast sensitivity of ICG stained images. Clear images of macula were captured by iOCT in all eyes. The average surgical time was 35.5±8.2 min. On the last follow-up, 16 of 19 eyes with MF resolved. The mean CFT was 178.5±103.5 μm, the maxRT was 341.8±83.8.16 μm, and the mean logMAR BCVA was 0.35±0.22. The differences of CFT, maxRT and logMAR BCVA before and after surgery were statistically significant (t=4.181, 7.154, 5.129; P<0.001). Minimal invisible full thickness macular hole were detected in 2 eyes by iOCT and repaired with auto serum or ILM flap covering. There was no complication associated with the 3D viewing system. Conclusions 3D viewing system provides improved contrast and crystal clear macular image stain with ICG in pathological myopia. iOCT can detect the minimal invisible full thickness macular hole during surgery. Both may contribute to improved MF closure rate and BCVA.

To investigate changes in the angiotensin converting enzyme 2 (ACE2) and angiotensin (1-7) [Ang (1-7)] and to explore the role of ACE2-Ang (1-7)-Mas receptor axis in hypertension with heart failure with preserved ejection fraction (HFPEF).
 Methods: A total of 70 patients with primary hypertension and preserved left ventricular ejection fraction (LVEF>50%) were recruited and patients were divided into a hypertension group (HBP) and a heart failure with preserved ejection fraction group (HFpEF) according to the diagnostic criteria of HFpEF. Thirty-five healthy participants were selected randomly as a control group. Enzyme linked immunosorbent assays (ELISA) method was used to detect concentration of Ang (1-7), ACE2, angiotensin II (Ang II), brain natriuretic peptide (BNP) in plasma. Male Sprague- Dawley (SD) rats was randomly divided into 2 groups: An HFpEF group (n=16) and a sham group (n=8). Rats (n=8) in the AAC group were given Ang (1-7) [0.5 mg/(kg.d), intraperitoneally] for 6 weeks, and the rest were given equal dose normal saline. Then all the rats were killed, and the hearts were taken out for hematoxylineosin (HE) staining. The protein expressions of angiotensin converting enzyme (ACE), ACE2, and Mas receptor were detected by Western blot.
 Results: The BNP and Ang II were significantly increased in the HBP group and the HFpEF group compared with the control group (P<0.01). There were not significantly different in levels of ACE2 and Ang (1-7) between the HBP group and control group (P>0.05), whereas those levels were significantly increased in the HFpEF group compared with the HBP group and control group (P<0.01). HE staining showed obvious hypertrophy of myocardial cell in the AAC group compared with the sham group. Hypertrophy of myocardial cell in the AAC+Ang (1-7) group was significantly higher than that in the AAC group. Expressions of ACE, ACE2, and Mas receptor proteins were significantly higher in the AAC group than those in the sham group (P<0.05), while the expressions of ACE2 and Mas receptor proteins in the AAC+Ang (1-7) group were significantly higher than those in the AAC group (P<0.05). There was no significant difference in the ACE protein expression between groups (P>0.05).
 Conclusion: ACE2 and Ang (1-7) are important predictive factors for the severity of heart failure and myocardial remodeling of HFpEF with hypertension; ACE2-Ang (1-7)-Mas receptor axis may play a protective role in preventing myocardial remodeling in HFpEF with hypertension.
Angiotensin I ; physiology ; Angiotensin II ; Animals ; Atrial Remodeling ; physiology ; Case-Control Studies ; Enzyme-Linked Immunosorbent Assay ; Heart Failure ; metabolism ; physiopathology ; Humans ; Hypertension ; metabolism ; physiopathology ; Male ; Peptide Fragments ; physiology ; Peptidyl-Dipeptidase A ; physiology ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Receptors, G-Protein-Coupled ; physiology ; Stroke Volume ; Ventricular Function, Left ; physiology ; Ventricular Remodeling ; physiology

This study was aimed to observe the effect of Compound Shi-Chang-Pu (CSCP) granula on behavior, structure changes of hippocampus with epileptic seizure of mice induced by pentyenetetrazole (PTZ). Sixty Kunming mice, which were half male and half female, were randomly divided into 6 groups, which were the blank control group, animal model, phenytoin (PHT) group, high-dose CSCP (4 000 mg·kg-1) group, middle-dose CSCP (2 000 mg·kg-1) group and low-dose CSCP (1 000 mg·kg-1) groups. The blank group and model group were given intragas-tric administration the same volume of saline, the others animals treated with continuous oral administration of drugs for 7 days. Intraperitoneal injection of PTZ (80 mg·kg-1) was given 1 h after the last medication to establish the a-cute epilepsy model (expect the blank control group). Observation was made on the influence of CSCP on incubation period, behavior degree and times of epileptic seizure among PTZ induced epilepsy mice, the structure changes of mice were detected by the brain tissue HE staining. The results showed that CSCP can improve the degree of seizure attack, prolong the incubation period of mild attack, and decrease Ⅳ and Ⅴ degree epileptic seizure, the PTZ in-duced epilepsy mice could damage the structure of hippocampus, reduce the number of cells, PHT and CSCP could ameliorate these changes. It was concluded that CSCP had certain inhibition on epileptic seizure mice induce by PTZ and ameliorate the damage of hippocampus. The antiepileptic mechanism still requires futher study.

OBJECTIVE: To determine the correlation between interleukin-18 (IL-18) level and Global Registry of Acute Coronary Events (GRACE) risk score as well as risk stratification in patients with acute coronary syndrome (ACS), and to determine the clinical prognostic value of IL-18 for major adverse cardiac events (MACE) in ACS patients. METHODS: A total of 150 ACS patients were subjected to risk assessment and stratification with GRACE risk score. All ACS patients received conventional treatments and MACE was recorded. Plasma IL-18 was measured by enzyme-linked immunosorbent assay and the relationship between plasma IL-18 level and GRACE scores in ACS patients was analyzed. Predictive accuracy of IL-18 level and GRACE risk score for MACE were determined by receiver operating characteristic curve and the corresponding area under the curve. RESULTS: According to GRACE risk stratification, IL-18 level was significantly elevated in the high risk group (>140) compared with that in the middle risk group (109-140; P<0. 05), while IL-18 level was significantly elevated in the middle risk group compared with that in the low risk group (≤108; P<0. 05). According to the IL-18 level, patients were stratified into 4 groups by quartile (from the lowest to the highest, Q1-Q4). Compared with Q1-Q3 groups, the GRACE risk score and percentage of high risk patients were the highest in the Q4 group (P<0.05). Receiver operating characteristic curve analysis showed that IL-18 level was positively related with GRACE risk score and that the area under the curve of IL-18 level and GRACE risk score for predicting MACE in hospital patients were 0.887 and 0.914, respectively. CONCLUSION Both IL-18 level and GRACE risk score are valuable parameters for risk of MACE in patients with ACS. IL-18 may be an important biomarker in the prognosis of ACS patients.
Acute Coronary Syndrome ; diagnosis ; Biomarkers ; blood ; Enzyme-Linked Immunosorbent Assay ; Humans ; Interleukin-18 ; blood ; Prognosis ; ROC Curve ; Risk Assessment ; Severity of Illness Index

OBJECTIVE: To investigate the relationship between insulin-like growth factor-1 (IGF-1) in the serum and the vascular endothelial function in patients with hypercholesterolemia and the underlying mechanism. METHODS: We examined the flow-mediated arterial diastolic function (FMD), the levels of IGF-1, asymmetric dimethylarginine (ADMA), NO, and the activity of nitric oxide synthase (NOS) in the serum from 25 patients with hypercholesterolemia and from healthy controls. An endothelial cell injury model was established by incubation of the human umbical vein endothelial cells (HUVECs) with oxidized low-density lipoprotein (ox-LDL) for 24 hours. Cells were treated with IGF-1 30 min before ox-LDL treatment. The levels of ADMA, NOS, and NO in the cell supernatant, the activity of dimethylarginine dimethylamine hydrolase (DDAH) in the cell lysate were measured. Beta-galactosidase staining was used to assess the degree of endothelial cell senescence by calculating the senescence rate of cells. RESULTS: Compared with the control group, the FMD, the levels of IGF-1 and NO, and the activity of NOS in the serum from patients with hypercholesterolemia decreased significantly accompanied with a dramatic increase at ADMA level. Multiple linear regression analysis showed that the change in IGF-1 was positively correlated with FMD while the change in ADMA was negatively correlated with FMD. Compared with the control group, ox-LDL treatments significantly decreased the activities of DDAH and NOS, and the level of NO, accompanied with an increase in ADMA. Betagalactosidase staining showed that the senescence rate of cells increased in the ox-LDL group. The effect of ox-LDL on HUVECs was significantly attenuated at the presence of IGF-1. CONCLUSION The decrease in IGF-1 in the peripheral blood may contribute to vascular endothelial dysfunction in patients with hypercholesterolemia. IGF-1 can protect HUVECs against ox-LDL-induced senescence, which is likely involved in the regulation of DDAH/ADMA pathway.
Adult ; Arginine ; analogs & derivatives ; blood ; Case-Control Studies ; Cells, Cultured ; Endothelium, Vascular ; physiology ; Female ; Human Umbilical Vein Endothelial Cells ; cytology ; Humans ; Hypercholesterolemia ; blood ; physiopathology ; Insulin-Like Growth Factor I ; metabolism ; physiology ; Lipoproteins, LDL ; pharmacology ; Male ; Middle Aged ; Nitric Oxide ; blood ; Protective Agents ; metabolism ; Vasodilation ; physiology

Objective To study the detection characteristics of methicillin-resistant Staphylococcus aureus and methicillin-resistant coagulase-negative staphylococcus.Methods Disks with 1 ?g of oxacillin and 30 ?g of cefoxitin were used to detect the inhibition zone of staphylococcus aureus and coagulase-negative staphylococcus at both 35℃ and 30℃ according to the method and breakpoint recommended by CLSI.The agar surface of oxacillin plate with sodium chloride was spotted.mecA gene was amplified by PCR.Results For detection of MRSA, disks of oxacillin and cefoxitin at 30℃ have the same sensitivity of 100%, however, the sensitivity of cefoxitin( 94.7%) is a little higher than that of oxacillin (93.3%) at 35℃. For detection of MRCNS, the sensitivity of 100% can be obtained by disks of both oxacillin and cefoxitin at both 30℃ and 35℃.The sensitivity and specificity of oxacillin plate with sodium chloride are the same as those of disks of oxacillin and cefoxitin at 30℃ for detection of MRSA, its sensitivity is lower than that of disks for detection of MRCNS.Conclusion The detection of methicillin-resistant Staphylococcus can be improved by the use of cefoxitin disk.