Objective To find out the protective effects of angiotensin Ⅱ recepter antagonist(ATRA)of Losartan and the calcium channel blockade(CCB)of Amlodipine on the SHR rat kidney. Methods The rats were divided into 3 groups,one group received Losartan(30 mg?kg -1 ?d -1 ),another group Amlodipine(10 mg?kg -1 ?d -1 ),for 3 months, while the control group received only water. All rats were tested for blood pressure(BP),proteinuria(UP),angiotensin(ATⅡ),endothelin(ET),kaluretic peptide(KP),atrial natriuretic peptide(ANP),aldosterone(Ald)and the pathological renal lesions,the expression of collagen Ⅳ(CoⅣ)and laminin(LM)were observed in SHR and Wistar kyoto(WKY)rats before and after the treatment. Results Losartan and Amlodipine not only significantly lowered the BP,24 h UP and pathological renal injuries,modulated the relaxation contraction of vascular substances in blood,but also significantly lessened the expression of CoⅣ and LM and ameliorated the glomerular sclerosis in SHR. Conclusions The modulation of Losartan and Amlodipine on the ratio of relaxative and contractive vascular substances in blood and on the extracellular matrix(ECM) metabolism through the ATⅡ, Ald and ET pathways may be one of the mechanism of ATRA and CCB on ameliorating the glomerular sclerosis.

AIM:NLRP3 inflammasome was identified as the cellular machinery responsible for activation of inflammatory processes .The present study investigated whether the activation of NLRP 3 inflammasomes contributes to hyperhomocysteinemia ( HHcy)-induced in-flammation and atherosclerosis .METHODS:ApoE-/-mice were fed regular diet , high fat ( HF) diet or HF plus high methionine (HM) diet for 10 weeks.NLRP3 shRNA or scramble shRNA viral suspension was injected twice at the 2nd and the 6th weeks after HFHM treatment.The whole aortas and aortic root sections were stained with Oil Red O for atherosclerotic lesion .Plasma lipids, ho-mocysteine ( Hcy) , IL-1βand IL-18 levels were measured .We also examined the effect of Hcy on NLRP 3 inflammasomes activation in THP-1 differentiated macrophages in the presence or absence of NLRP 3 siRNA, caspase-1 inhibitor Z-WEHD-FMK, or antioxidant N-acetyl-L-cysteine ( NAC) .RESULTS:HFHM treatment induced HHcy in ApoE-/-mice.Increased plasma levels of IL-1βand IL-18, aggravated macrophage infiltration into atherosclerotic lesion , and accelerated development of atherosclerosis were detected in HHcy mice, which were associated with the activation of NLRP 3 inflammasomes.Silencing the NLRP3 gene significantly suppressed NLRP3 inflammasomes activation , reduced plasma levels of proinflammatory cytokines , attenuated macrophage infiltration , and improved HHcy-induced atherosclerosis .Moreover, we found that Hcy activated NLRP3 inflammasomes and promoted subsequent production of IL-1βand IL-18 in macrophages, which were blocked by NLRP3 gene silencing, Z-WEHD-FMK, or NAC.CONCLUSION:These data suggest that the activation of NLRP 3 inflammasomes contributes to HHcy-induced inflammation and atherosclerosis .Hcy activates NLRP3 inflammasomes in reactive oxygen species dependent pathway in macrophages .

Objective To explore the effects of estrogen on apolipoprotein M ( apoM ).Methods ApoM mRNA was assayed in HepG2 cells by RT-PCR after incubation of estrogen with or without estrogen receptor antagonist at different concentrations and durations.SD female rats were divided into five groups:OVX group,Sham group,OVX+ EB group,normal group and normal + EB group.From a week of being operated,the rats were injected subcutaneously estradiol beuzoate or vehicle.After 12-hrs fasting,serum levels of triglycerides (TG),LDL-cholesterol,HDL-cholesterol,total cholesterol ( TC ) at months 1,2 and 3 after operation were measured.The expression of apoM in rats was detected by using real time RT-PCR and Western blot.Results Estrogen increased mRNA levels of apoM and apoAI in the HepG2 cells with a dose- and time-dependent manner,which could be abolished by addition of estrogen receptor antagonist.Serum apoM,TG,TC,HDL and LDL levels were significantly increased in the ovariectomized or normal rats which received estrogen treatment than those in OVX or normal group rats at month 1 after treatments.Conclusions Estrogen upregulates apoM expression via its receptor.

Objective To investigate the risk factors for lower extremity peripheral arterial disease (LEPAD) in elderly patients with Type 2 diabetes mellitus(T2DM).Methods To detect ankle brachial index (ABI) of 356 elderly patients with T2DM,and analyze whether risk factors had correlation with ABI.Results We found that age,systolic blood pressure,HbAlc,2-hours post-prandial (2hpp) plasma glucose had inverse correlation,yet 2hpp C-peptide plasma level,2-hpp insulin level had positive correlation with ABI by bivariate correlation test.Conclusions Age,systolic blood pressure,2hpp plasma glucose,2hpp C-peptide plasma level,2hpp insulin level were related with lower extremity arterial disease in the elderly with T2DM,among which age was the most important risk factor for LEPAD.

Objective To study the mental health condition of occupational female and influencing factors of mental health. Methods 827 occupational females in Dongguan city were investigated using the questionnaires, the contents included the basic personal information, mental health condition and influencing factors of mental health.Results The results showed that there existed higher ratio of mental disorder in people of age over 50 years, post-graduate educational background, monthly income levels of 4001 to 5000 yuan and divorced occupational females.Moreover, the influential factors on mental health of occupational females were correlated with age, culture degree,family population and society. Conclusion We should pay more attention to occupational females and take effective measure to relieve their mental stress. This is the demands of woman as well as society.

The clinical practice of diabetes management is facing challenge in China,old anti-diabetic drugs such as sulfonylureas have been used for more than 60 years, and they are still valuable in diabetes management because of their remarkable hypoglycemic effect,as well as good safety,clear adverse events and cost-effectiveness.

Objective To evaluate the clinical and radiographic characteristics and function of erosive hand osteoarthritis (EOA) patients. Methods Data were obtained from 19 patients with EOA, including their social conditions, clinical conditions, radiographic scores and hand function evaluation. The number of hand osteoarthritis (HOA) patients was 312. The control group consisted of non-EOA patients with hand osteoarthritis with a ratio of 4:1 to EOA patients. A non-parameter test analysis was performed. All data were analyzed by SPSS 23.0 statistical analysis, t test, χ2 test, Fisher exact probility and Spearman's correlations analysis were used for statistical analysis. Results Totally data of 19 patients were collected. Eighteen were female. Onset age was (56±8). Average duration was 56 (12~120) months. FIHOA scores of all the EOA patients were at least 5. All the erosions of 39 joints were characteristically central and erosive changes in 7 joints (18%) showed up as gull-wing. Among 39 erosive joints, including 12 (31%) E and 27 (69%) R, 34 (87%) distal interphalangeal joints were involved. Data analysis found out that EOA patients had longer disease duration (Z=2.610, P=0.009), more severe K-L level (44 ±11 vs 26 ±7, t=7.134, P<0.01), higher AUSCAN total score (28±6 vs 21±7, t=3.781, P<0.01) and higher AUSCAN function score (18±6 vs 12±6, t=4.042, P<0.01). The differences of ESR and CRP were not significant between EOA and non-EOA patients. Conclusion Erosions seen in EOA patients are centrally located gull-wing in the DIP joints. EOA patients have longer duration, more severe radiographic damage and worse joint function.

Objective:The common protocol deviation (PD) in clinical trials of drugs for rheumatic diseases were analyzed to provide reference for improving the quality of clinical trials and protecting the safety and rights of subjects.Methods:Protocol deviation (PD) reports of completed projects conducted by Department of Rheumatology and Immunology, the Second Hospital of Shanxi Medical University, from 2017 to 2021 were collected and sorted out for analysis. Results:The common PD and proportion of deviation were deviation from protocol study procedures (25.4%, 44/173), low medication compliance (23.7%, 41/173), visits out of the scheduled visit dates or the tests or examinations out od the inspection window period (19.1%, 33/173), missed visit or missed laboratory tests (17.9%, 31/174), using of prohibited drugs (9.2%, 16/173) and violation of inclusion criteria or exclusion criteria (4.6%, 8/173). 135 cases were mild and 38 cases severe deviation. PPS was eliminated in 5 subjects during statistical analysis.Conclusion:①Investigator training should be strengthened and the operability should be taken into account in clinical trial design. In the implementation process, the inclusion and exclusion criteria should be strictly followed and the should adherent to study procedures. ②The institution should actively promote the development of hospital information system to reduce investigator associated PD. ③The education and management of subject should be strengthened to ensure their compliance and improve the quality of clinical trials to protect the safety and rights of subjects. ④Institute should strengthen the management of trail supervisors and emphasis on problems identification during inspections.

OBJECTIVETo investigate the association between genetic polymorphisms of proximal promoter region of apolipoprotein M (apoM) gene and susceptibility of coronary artery diseases (CAD) in Han Chinese population.

METHODSTwo pairs of primers were designed according to the sequence (GenBank accession nos. EU030444.1) and the PCR products of apoM proximal promoter region were directly sequenced. Two hundred and six patients [165 males, mean age (61.9 ± 9.2) years old] diagnosed with CAD according to the results of angiography (a lesion was classed as being significant when stenosis was more than 50%) were enrolled in the present study, 209 age- and gender-matched patients[157 males, mean age (60.4 ± 9.1) years old] without CAD according to the results of angiography were selected as the control group. The allelic frequencies and genotype distributions of polymorphism in CAD and non-CAD patients were analyzed. Furthermore the wide-type and mutant promoter region of apoM were cloned into the luciferase expression vector pGL3, respectively. Luciferase reporter assay was used to detect the activity of apoM promoter.

RESULTSA new deletion mutation -724delC in apoM promoter was found. The frequency of Del C allele was 8.0% in CAD patients and only 4.1% in the non-CAD controls (OR = 2.054, 95%CI 1.125-3.749, P = 0.017). The mean TC level was lower in groups with wide-type homozygotes compared to the mutant allele carriers [ (6.04 ± 0.90) mmol/L vs. (4.95 ± 1.00)mmol/L, P < 0.01]. -724delC mutant showed obvious decreased luciferase activities (1.13 ± 0.25 vs. 2.11 ± 0.15, P = 0.009).

CONCLUSIONIt is reasonable to speculate that -724delC could affect the activity of the apoM promoter and downregulate apoM expressions, therefore, influence the susceptibility of CAD in this patient cohort.

Aged ; Apolipoproteins ; genetics ; Apolipoproteins M ; Asian Continental Ancestry Group ; genetics ; Coronary Artery Disease ; genetics ; Female ; Genetic Predisposition to Disease ; Humans ; Lipocalins ; genetics ; Male ; Middle Aged ; Polymorphism, Single Nucleotide ; Promoter Regions, Genetic

Objective:Partial stereotactic ablative boost radiotherapy(P-SABR)is a method to deliver SABR boost to the gross tumor boost volume(GTVb), followed by conventionally fractionated radiotherapy to the whole tumor area(GTV). GTVb is the max volume receiving SABR while ensuring the critical organ-at-risk(OAR)falloff to 3 GyE/f. We investigated the potential advantage of proton therapy in treating bulky non-small cell lung cancer(the tumor length greater than 8 cm).Methods:Nine patients with bulky NSCLC treated with photon P-SABR in our institute were selected. For the treatment planning of proton therapy, the GTVb target area was gradually outwardly expanded based on the photon GTVb target area until the dose to critical OARs reached 3 GyE/f. The GTV and CTV areas remained the same as photon plan. A proton intensity-modulated radiation treatment plan(proton-IMPT), a photon intensity-modulated radiation treatment plan(photon-IMRT)and a photon volumetric modulated arc therapy(photon-VMAT)were created for each patient, respectively. The dosimetric parameters of different treatment plans were compared.Results:The volume ratio of GTVb-photon and GTVb-proton to GTV was(25.4±13.4)% and(69.7±30.0)%,respectively( P<0.001). In photon-IMRT, photon-VMAT, and proton-IMPT plan groups, the mean dose of CTV was(76.1±4.9)Gy, (78.2±3.6)Gy, and(84.7±4.9)Gy, respectively; the ratio of tumor volume with Biologic Effective Dose(BED)≥ 90 Gy to GTV volume was(70.7±21.7)%, (76.8±22.1)%,and(97.9±4.0)%,respectively. The actual dose and BED to the tumor area of the proton-IMPT plan group were significantly higher than those of the photon plan group(both P<0.05). Besides, the OARs dose was significantly decreased in the proton-IMPT group, with(49.2±22.0)%, (56.8±19.0)% and(16.1±6.3)% of the whole lung V5 for photon-IMRT, photon-VMAT and proton-IMPT, respectively(all P<0.001). Conclusions:Larger GTV boost target volume, higher BED and reduced OARs dose can be achieved in proton plans compared with photon plans. Proton P-SABR is expected to further improve the local control rate of bulky NSCLC with fewer adverse effects.