Objective To observe the effects of rosuvastatin on the homocysteine (Hcy)-induced expression of matrix metalloproteinase 2 (MMP 2) and cell migration in rat vascular smooth muscle cells (VSMCs), and to explore the possible mechanism of Hcy-induced atherosclerosis and the role of statins in reversing atherosclerosis. Methods In one cell culture plate, the cultured rat VSMCs were incubated with different concentrations of Hcy (0, 50, 100, 500, 1000 μmol/L and 5000 μmol/L) in vitro for 24 h, 48 h and 72 h. And in another cell culture plate, the different concentrations of rosuvastatin (10-9, 10-8, 10-7, 10-6, 10-5 mol/L and 0 mol/L) were added to the cultured rat VSMCs (while the concentration of Hcy was 1000 μmol/L). The MMP 2 expression and enzyme activity were determined by gelatin zymography and Western blotting. The effects of Hcy and rosuvastatin on cell migration and invasiveness of VSMCs were observed. Results Hcy (50-5000 μmol/L) increased the protein expression, and Hcy (50-1000 μmol/L) increased enzyme activity of MMP 2 significantly. But Hcy (5000 μmol/L) inhibited activity of MMP 2 (F=9.31, 6.44 and 5.97, all P＜0.05). Rosuvastatin (10-9-10-5 mol/L) inhibited Hcy-induced expression and enzyme activity increasing of MMP 2. The counts of cell migration of VSMCs were 18.32±2.17, 32.68±4.34, 44.75±4.08, 61.39±5.21, 79.74±5.54 and 90.78±5.83, while the concentration of Hcy was 0, 50, 100, 500, 1000 μmol/L and 5000 μmol/L respectively (F=5.31, P＜0.05). The counts of cell migration of VSMCs were 79.74±5.54, 62.53±6.41, 48.37±5.66, 31.41±4.79, 19.27±3.62 and 11.17±2.33, while the concentration of rosuvastatin was 10-9, 10-8, 10-7, 10-6 and 10-5 mol/L respectively (F=4.99, P＜0.05). Rosuvastatin could decrease the stimulation of Hcy-induced migration of VSMCs. Conclusions Hcy can influence the MMP 2 protein expression/activity in VSMCs, and rosuvastatin can inhibit augmentation of Hcy-induced MMP 2 expression/activity and migration of VSMCs. It may be one of the multiple-effects of rosuvastatin reducing atherosclerosis.

Objective:To explore the relationship between the type of mutation and clinical features, prognosis, and clinical characteristics of chronic granulomatous disease (CGD) caused by compound heterozygous mutations in the NCF2 gene in children. Methods:The clinical data of 1 case of neonatal CGD caused by compound heterozygous mutations of NCF2 gene at Tianjin Children′s Hospital in August 2019 was analyzed, and domestic and international literatures were searched to summarize the clinical characteristics, gene mutation type and prognosis of CGD caused by NCF2 mutation. Results:The diagnosis of CGD was confirmed by the presence of compound heterozygous mutations c. 196_197insA (p.Arg66Glnfs23X) and c. 1180T>G (p.Tyr394Asp) in the NCF2 gene, accompanied with the clinical manifestations of fever, cough, multiple clumps and nodules in the chest CT at 25 days after birth, and the neutrophil respiratory burst test stimulation index(SI) 23.This new mutation was not reported in the Human Genetic Mutation Database.The child had a residual portion of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activity and was followed up until the age of 9 months with an antifungal drug without recurrent infection.A total of 101 cases of CGD patients with NCF2 gene mutation were reported in domestic and international databases.Totally, 33 cases had SI results, with 22 cases below 3, 11 cases above 3, and 8 cases of missense mutations. Conclusions:c. 196_197insA and c. 1180T>G are new mutations in NCF2 gene that can lead to CGD.CGD patients containing missense mutations in the NCF2 gene may have more residual NADPH oxidase activity.

Objective:To investigate the value of proton magnetic resonance spectroscopy (1H-MRS) on the diagnosis of SCA3/MJD,and to calculate the correlation between 1H-MRS ratio and the clinical score.Methods:Sixteen patients with SCA3/MJD and 19 healthy volunteers were scanned with 1H-MRS.The data of N-acetyl aspartate,creatine,choline-containing compounds,myoinositol,NAA/Cr,Cho/Cr,and mI/Cr ratio were collected,which were grouped for comparative study.The onset patients with SCA3/MJD were evaluated with the International Cooperative Ataxia Rating Scale and Scale for the Assessment and Rating of Ataxia,the correlation between NAA/Cr,Cho/Cr or mI/Cr ratio and the clinical score was calculated.Results:The NAA/Cr in the pons and cerebellar dentate nucleus from the onset patients with SCA3/MJD was significantly reduced compared to that in the normal control group.The NAA/Cr in the cerebellar dentate nucleus of onset patients with SCA3/MJD was obviously correlated with ICARS.Conclusion:SCA3/MJD lesions are mainly located in the cerebellum and brainstem,where gray and white mater are also involved.The cerebellar dentate nucleus may be the earliest involved area.There is a correlation between the ICARS and the cerebellar lesion degree.The ICARS reflects the severity of clinical manifestations.1H-MRS is useful in the diagnosis of SCA3/MJD.

Objective To explore the correlation between CAE and the ratio of white blood cell count to mean platelet volume ratio(WMR)in elderly patients.Methods A retrospective analysis was conducted on 238 patients who underwent coronary angiography(CAG)between January 2018 and January 2023 in Department of Cardiology of Tianjin First Central Hospital.According to the results of CAG and patient's age,they were divided into in elderly CAE group(age ≥65 years,100 cases)and non-elderly CAE group(age＜65 years,138 cases).Another 127 age-matched elderly individuals with normal coronary artery(age ≥65 years)served as normal con-trol group.The WMR levels were measured in all participants.Results The elderly CAE group had significantly higher WMR than the non-elderly CAE group and the normal control group(745.50±237.46 vs 672.43±194.52 and 610.11±144.22,P=0.000).Spearman correlation analy-sis showed that WMR was positively correlated with platelet count,neutrophil count and high-sensitivity C-reactive protein level(r=0.380,P=0.000;r=0.819,P=0.000;r=0.283,P=0.000).Multiple logistic analysis indicated that readmission,male,TC and WMR were significantly associated with CAE in elderly patients.ROC curve analysis revealed that the value of WMR to distinguish the presence of CAE in elderly patients was 0.604(95％CI:0.531-0.677,P=0.006).Conclusion Elevated WMR might be a cost-effective monitor in elderly CAE patients.

Objective To study the application value of pneumonia severity index high-risk score (PSI-HR) in high risk patients and neutrophil-to-lymphocyte ratio (NLR) in the condition evaluation of the pa-tients with respiratory tract infection in ICU.Methods The clinical data of the patients with lower respiratory tract infection hospitalized in the department of intensive care medicine of this hospital from January 2020 to July 2023 were retrospectively analyzed.According to the ICU outcomes,the patients were divided into the im-provement group (n=77) and the poor prognosis group (n=25),and the receiver operating characteristic (ROC) curve was drawn to analyze the evaluation value of PSI-HR score combined with NLR,NLR,PSI-HR score,PSI-HR grade and PSI grade in the prognosis of the patients with lower respiratory tract infection. Results The case fatality rates of the patients with different grades of PSI were 40.00％ (16/40) for the grade 5,18.75％ (6/32) for the grade 4,22.22％ (2/9) for the grade 3 and 4.76％ (1/21) for the grade 2,re-spectively.There was no significant correlation between different PSI grades and case fatality rate (r=0.911,P=0.089).The case fatality rates of different grades of PSI-HR were 75.00％ (3/4) for the grade 6,46.67％ (7/15) for the grade 5,28.57％ (6/21) for the grade 4,17.24％ (5/29) for the grade 3,and 12.12％ (4/33) for the grade 2,respectively,and the PSI-HR grade was positively correlated with the case fatality rate of the patients (r=0.955,P=0.011).The area under the ROC curve (AUC) of predicting the prognosis of the pa-tients with lower respiratory tract infection from great to small was 0.828(95％CI:0.717-0.938,P<0.05) for PSI-HR score combined with NLR,0.754 (95％CI:0.637-0.871,P<0.05) for NLR,0.744 (95％CI:0.636-0.852,P<0.05) for PSI-HR score,and 0.706 (95％CI:0.584-0.829,P<0.05) for PSI-HR grade and 0.695 (AUC=0.695,95％CI:0.582-0.807,P<0.05) for PSI grade.Conclusion The PSI-HR grade has good correlation with the case fatality rate of the patients with lower respiratory tract infection.The effi-ciency of PSI-HR grade combined with NLR for predicting the prognosis in the patients with lower respiratory tract infection in ICU is better than that of single index.

Objective:To investigate the clinical characteristics and etiology of pulmonary embolism in children, and to discuss the efficacy and safety of anticoagulation therapy.Methods:The data of 30 children with pulmonary embolism, who were treated with anticoagulation therapy in the Department of Pediatrics, Provincial Hospital Affiliated to Shandong First Medical University from January 2017 to December 2021, were analyzed retrospectively.The etiology, clinical characteristics, complications, outcomes and prognosis after anticoagulation treatment were analyzed.Results:There were 17 males and 13 females, with an average age of (8.95±2.58) years (age range: 4-13 years). The follow-up duration was 3-59 months.(1) The symptoms included cough in 30 cases (100.0%), fever in 29 cases (96.7%), shortness of breath in 27 cases (90.0%), chest pain in 15 cases (50.0%), hemoptysis in 9 cases (30.0%), bloody secretions under bronchoscopy but no hemoptysis in 4 cases (13.3%), and respiratory failure in 2 cases (6.7%). (2) The protopathy was Mycoplasma pneumoniae infection in 23 cases (76.7%), whose symptoms accorded with refractory Mycoplasma pneumoniae pneumonia.About 16 cases (53.3%) were positive for Mycoplasma pneumoniae drug resistance mutation 2063A>G or 2064A>G.Two cases (6.7%) had nephrotic syndrome.One case (3.3%) had purpura nephritis (nephrotic syndrome type). One case (3.3%) was lupus nephritis (nephrotic syndrome type). One case (3.3%) was hereditary protein S deficiency.One case (3.3%) had osteomyelitis and Staphylococcus aureus sepsis.One case (3.3%) had congenital heart disease.(3) Complications included limb thrombosis in 7 cases (23.3%), atrial thrombosis in 2 cases (6.7%), thoracic and abdominal deep venous thrombosis in 2 case (6.7%), cerebral infarction in 2 cases (6.7%), and splenic infarction in 1 case (3.3%). (4) Imaging examination showed that 30 children had lung consolidation/atelectasis (100.0%), and 24 cases had pleural effusion (80.0%). (5) Coagulation function examination suggested D-dimer increased to ≥ 5 mg/L in 21 cases (70.0%). (6) One case (3.3%) was given thrombolytic therapy with urokinase at the acute stage.Nine cases (30.0%) were treated with heparin/low molecular weight heparin.Twenty-one cases (70.0%) first received anticoagulation therapy with heparin/low molecular weight heparin and later took oral anticoagulant.Four cases (13.3%) were treated with Warfarin and 17 cases (56.7%) with Rivaroxaban.The anticoagulant treatment lasted 1-9 months.No recurrence of embolism or sequelae of chronic thromboembolic pulmonary hypertension was observed. Conclusions:Infection, especially Mycoplasma pneumoniae infection, is the main cause of pulmonary embolism in children.The symptoms of pulmonary embolism in children are atypical, so it is difficult to distinguish this disease from primary underlying diseases.Bronchoscopy can help find occult pulmonary hemorrhage.Unexplained shortness of breath in children of any age suggests the possibility of pulmonary embolism.Combination of clinical symptoms and necessary examination contribute to early diagnosis of pulmonary embolism.Then selection of appropriate anticoagulant drugs and timely anticoagulant therapy can improve the prognosis of children.

Objective:To observe the effect of early rehabilitation exercise on blood pressure of elderly patients with septic shock.Methods:A single-center, prospective, randomized controlled study was conducted in elderly patients with septic shock who were hospitalized in the department of critical care medicine of Huangshan Shoukang Hospital (High-tech Zone Central Hospital of Huangshan) from December 2018 to November 2020. According to the principle of simple random, all patients were divided into control group and intervention group. Both groups were treated with lower limb barometry to prevent deep vein thrombosis, 3 times a day, 30 minutes each time. After comprehensive treatment in the intensive care unit (ICU), the severity of patients was gradually improved, the hemodynamics was relatively stable, and the norepinephrine was reduced to 0.5 μg·kg -1·min -1. The control group continued to receive lower limb barometric treatment without rehabilitation training, while the intervention group began rehabilitation training when the dose of norepinephrine was reduced to 0.5 μg·kg -1·min -1. The duration of norepinephrine use, the length of ICU stay, and the occurrence of adverse events during rehabilitation training in intervention group was recorded. Results:Seventy-two patients were included in the final analysis, 35 in intervention group and 37 in control group. There was no significant difference in gender, age, Oxford acute severity of illness score (OASIS), acute physiology and chronic health evaluationⅡ (APACHEⅡ), mean arterial pressure (MAP) of 3 times and underlying diseases between two groups. Compared with control group, the length of ICU stay and duration of dose of norepinephrine ≤0.5 μg·kg -1·min -1 in intervention group were significantly shorter [length of ICU stay (hours): 193.0 (145.5, 312.0) vs. 242.5 (180.0, 483.5), P < 0.05; duration of dose of norepinephrine ≤0.5 μg·kg -1·min -1 (hours): 120.0 (72.0, 144.0) vs. 144.5 (120.0, 192.0), Z = 2.976, P = 0.003]. In intervention group, 35 patients did not show acute myocardial infarction, arrhythmia, syncope, central venous catheter detachment, and gastric tube detachment during the rehabilitation period, except 1 patient suffered from naked hematuria due to urinary catheter traction, which disappeared the next day after symptomatic treatment. Conclusion:The early rehabilitation exercise was beneficial to the recovery of autonomic blood pressure in elderly patients with septic shock, shorten the time of norepinephrine use and ICU stay.

OBJECTIVETo examine apoptosis of SMMC-7721 hepatocarcinoma cells induced by total flavonoids of Oxytropis falcata (TFOF) and its preliminary mechanism.

METHODSMMC-7721 cells were treated for 24 h with TFOF in different concentrations. Inhibition on proliferation of SMMC-7721 cells was assessed by MTT assay. The morphology of treated SMMC-7721 cells was observed by optical microscope. Effect of TFOF on the nuclear morphology of cells was analyzed using Hoechst 33258 staining by fluorescence microscope. Annexin V-FITC/PI staining and flow cytometric measurement were used for investigating the effect of TFOF on induction of apoptosis in SMMC-7721 cells and cell cycle analysis.

RESULTThe results of MTT assay showed that TFOF could induce cytotoxicity in SMMC-7721 cells in a dose-dependent manner. Hoechst 33258 staining analysis indicated that TFOF caused typical characteristics of apoptotic programmed cell death, such as cell shrinkage, apoptotic body formation etc. Flow cytometric analysis demonstrated that TFOF caused a dose-dependent apoptosis of SMMC-7721 cells and arrested cell cycle in G1 phase.

CONCLUSIONIt suggested that TFOF inhibit proliferation of SMMC-7721 cells by inducing apoptosis of the cells and arresting cell cycle in G1 phase.

Antineoplastic Agents, Phytogenic ; pharmacology ; Apoptosis ; drug effects ; Carcinoma, Hepatocellular ; drug therapy ; physiopathology ; Cell Cycle ; drug effects ; Cell Line, Tumor ; Drugs, Chinese Herbal ; pharmacology ; Humans ; Liver Neoplasms ; drug therapy ; physiopathology ; Oxytropis ; chemistry

Objective:To investigate the inhibitory effect and molecular mechanism of microRNA-30d (miR-30d) in the process of proliferation, migration and invasion of malignant mesothelioma cell line MSTO-211H.Methods:In April 2017, the human MSTO-211H cells was used to establish miR-30d overexpressed MSTO-211H cell model by transfection of miR-30d mimics. The qRT-PCR was performed to detect the expression level of miR-30d in the cells transfected miR-30d mimics. The effects of miR-30d on the proliferation, apoptosis, migration and invasion of MSTO-211H cells were analyzed by CCK-8 experiment, flow cytometry, cell scratch experiment and Transwell method.Results:After transfection of miR-30d, the expression level of miR-30d in the MSTO-211H+miR-30d cells group was significantly higher than MSTO-211H+miR NC cells group ( P<0.01) . The cell activity of MSTO-211H+miR-30d group (105.13%±2.35%) was significantly lower than MSTO-211H+miR NC cells group (115.40%±1.35%) , and the level of apoptosis (3.97%±0.36%) was significantly higher than MSTO-211H+miR NC cells group (1.47%±0.10%) ( P<0.01) . The relative migration areas at 12 and 24 h of MSTO-211H+miR-30d cells group (9.35±3.16 μm 2 and 58.19±1.82 μm 2) were significantly lower than MSTO-211H+miR NC cells group (54.42 ±5.26 μm 2 and 88.32 ±1.96 μm 2) ( P<0.01) . Compared with the MSTO-211H+miR NC cells group, the numbers of cell migration and cell invasion were reduced in the MSTO-211H+miR-30d cells group ( P<0.01) . Conclusion:miR-30d can regulate the progression of malignant pleural mesothelioma by inhibiting the proliferation, apoptosis, migration and invasion of MSTO-211H cells.