Abstract It has been reported that some single-nucleotide polymorphisms (SNPs) are associated with the risk of Parkinson's disease (PD), but whether a combination of these SNPs would have a stronger ...association with PD than any individual SNP is unknown. Sixteen SNPs located in the 8 genes and/or loci ( SNCA , LRRK2 , MAPT , GBA , HLA-DR , BST1 , PARK16 , and PARK17 ) were analyzed in a Chinese cohort consisting of 1061 well-characterized PD patients and 1066 control subjects from Central South of Mainland China. We found that Rep1, rs356165, and rs11931074 in SNCA gene; G2385R in LRRK2 gene; rs4698412 in BST1 gene; rs1564282 in PARK17 ; and L444P in GBA gene were associated with PD with adjustment of sex and age ( p < 0.05) in the analysis of 16 variants. PD risk increased when Rep1 and rs11931074, G2385R, rs1564282, rs4698412; rs11931074 and G2385R, rs1564282, rs4698412; G2385R and rs1564282, rs4698412; and rs1564282 and rs4698412 were combined for the association analysis. In addition, PD risk increased cumulatively with the increasing number of variants (odds ratio for carrying 3 variants, 3.494). In summary, we confirmed that Rep1, rs356165, and rs11931074 in SNCA gene, G2385R in LRRK2 gene, rs4698412 in BST1 gene, rs1564282 in PARK17 , and L444P in GBA gene have an independent and combined significant association with PD. SNPs in these 4 genes have a cumulative effect with PD.
Diarrhea is a major medical problem in clinical practice. According to the theory of traditional Chinese medicine (TCM), different types of diarrhea should be treated with different TCM formulations ...based on the targeted medical condition. Dampness-heat diarrhea (DHD) is a serious diarrheal disease and Pulsatilla decoction (PD), a TCM, has been found effective against DHD.
The aim of this study was to clarify the mechanism of action of PD in DHD using an untargeted lipidomics strategy.
Wistar rats were randomized to four groups, including the control group, model group, PD groups and self-healing group. The PD groups were given a daily intragastric gavage of PD at doses of 3.76 g/kg. The rat model of DHD established by such complex factors as high-sugar and high-fat diet, improper diet, high temperature and humidity environment, drinking and intraperitoneal injection of Escherichia coli., which imitated the inducing conditions of DHD. Then the clinical symptoms and signs, blood routine, serum inflammatory cytokines levels and the histopathological changes of main organs were detected and observed to evaluate DHD model and therapeutic effect of PD. Lipid biomarkers of DHD were selected by comparing the control and model groups with the colon lipidomics technology and an ultra-high performance liquid chromatography (UHPLC) coupled with Q Exactive plus mass analyzer. Multivariate statistical analysis and pattern recognition were employed to examine different lipids within the colon of PD-treated rats.
The clinical symptoms and signs of the model rats were consistent with the diagnostic criteria of DHD. After treatment with PD, the clinical symptoms and signs of the rats with DHD were improved; the indexes of blood routine and inflammatory cytokines levels tended to be normal. The lipidomics profile of the model group were evidently disordered when compared to the control group. A total of 42 significantly altered lipids between the model-control groups were identified by multivariate statistical analysis. DHD may result from such lipid disorders which are related to glycerophospholipid metabolism, arachidonic acid (AA) metabolism, and sphingolipid metabolism. After PD treatment, the lipidomic profiles of the disorders tended to recover when compared to the model group. Twenty lipid molecules were identified and some glycerophospholipids and AA levels returned close to the normal level.
Glycerophospholipid metabolism may play an important role in the treatment of dampness-heat induced diarrhea using PD.
Pathological cardiac hypertrophy (CH) is driven by maladaptive changes in myocardial cells in response to pressure overload or other stimuli. CH has been identified as a significant risk factor for ...the development of various cardiovascular diseases, ultimately resulting in heart failure. Melanoma differentiation-associated protein 5 (MDA5), encoded by interferon-induced with helicase C domain 1 (IFIH1), is a cytoplasmic sensor that primarily functions as a detector of double-stranded ribonucleic acid (dsRNA) viruses in innate immune responses; however, its role in CH pathogenesis remains unclear. Thus, the aim of this study was to examine the relationship between MDA5 and CH using cellular and animal models generated by stimulating neonatal rat cardiomyocytes with phenylephrine and by performing transverse aortic constriction on mice, respectively. MDA5 expression was upregulated in all models. MDA5 deficiency exacerbated myocardial pachynsis, fibrosis, and inflammation in vivo, whereas its overexpression hindered CH development in vitro. In terms of the underlying molecular mechanism, MDA5 inhibited CH development by promoting apoptosis signal-regulating kinase 1 (ASK1) phosphorylation, thereby suppressing c-Jun N-terminal kinase/p38 signaling pathway activation. Rescue experiments using an ASK1 activation inhibitor confirmed that ASK1 phosphorylation was essential for MDA5-mediated cell death. Thus, MDA5 protects against CH and is a potential therapeutic target.
Introduction:
Diarrhea-predominant irritable bowel syndrome (IBS-D) significantly decreases the quality of life of patients and their families, and affects patients’ mental health. No specific ...western medications are available. Ancient classical Chinese medical texts have recognized Tongxie Yaofang (TXYF) as a therapy for diarrhea which is widely used in clinical practice. Standard TXYF prescription (S-TXYF) is composed of four herbal medicines:
Atractylodes macrocephala
Koidz. Asteraceae;
Rhizoma Atractylodis Macrocephalae
., Paeonia lactiflora Pall. Ranunculaceae; Paeoniae Radix Alba, Citrus × aurantium L. Rutaceae; Citri Reticulatae Pericarpium and Saposhnikovia divaricata (Turcz. ex Ledeb.) Schischk. Umbelliferae
; Saposhnikoviae Radix
. This review aimed to evaluate the therapeutic effects and safety of S-TXYF for IBS-D.
Methods:
Eight English and Chinese electronic databases were searched from their inception to 25 December 2021 for randomized controlled trials (RCTs) comparing S-TXYF with placebo, western medications or no treatment for IBS-D. The primary outcome was the global improvement of IBS-D symptoms. Data were analyzed using Cochrane’s Revman 5.4 software. Evidence certainty was assessed using the online GRADEpro tool for the primary outcome.
Results:
Eleven RCTs involving 985 adults with IBS-D were included. For global improvement of symptoms, S-TXYF was superior to western medication and placebo (moderate evidence by GRADE). Regarding the improvement of stool consistency, stool frequency and abdominal pain, S-TXYF was significantly effective than placebo. In addition, S-TXYF was superior to western medication on improving the quality of life and relieving anxiety. Six trials reported adverse events: five of them reported (non-serious) adverse events occurred in both groups, and one trial reported that 3 cases with adverse events (constipation, elevation in liver-enzyme, nausea) occurred in S-TXYF group and 3 cases with adverse events (abdominal distension, nausea) occurred in placebo group.
Conclusion:
Although current results showed that S-TXYF may have potential to treat IBS-D and its use appears to be safe, no a clear and confirmed conclusion can be drawn from our review as the overall inadequate design of the included trials reviewed. So more rigorous trials are warranted to establish confirmed evidence on its benefits and safety.
Abstract
Objective
Ni-Ti memory alloys are unusual materials for hard-tissue replacement because of their unique superelasticity, good biocompatibility, high strength, low specific gravity, low ...magnetism, wear resistance, corrosion resistance and fatigue resistance. The current study aims to evaluate its mechanical properties and provide biomechanical basis for the clinical application of the prosthesis.
Methods
Ten adult metacarpophalangeal joint specimens were randomly divided into a prosthesis group (n = 5, underwent metacarpophalangeal joint prosthesis) and a control group (n = 5, underwent sham operation). Firstly, the axial compression strength was tested with BOSE material testing machine to evaluate its biomechanical strength. Secondly, these specimens were tested for strain changes using BOSE material testing machine and GOM non-contact optical strain measurement system to evaluate the stress changes. Thirdly, fatigue test was performed between groups. Lastly, the mechanical wear of the metacarpophalangeal joint prosthesis was tested with ETK5510 material testing machine to study its mechanical properties.
Results
Axial compression stiffness in the prosthesis group was greater than that in the control group in terms of 30 ° and 60 ° flexion positions (P < 0.05). There was no statistically significant difference between two groups with regards to axial compression stiffness and stress change test (P > 0.05). In the fatigue wear test, the mean mass loss in the prosthesis group’s prosthesis was 17.2 mg and 17.619 mm
3
, respectively. The mean volume wear rate was 0.12%. There was no statistically significant difference in the maximum pull-out force of the metacarpal, phalangeal, and polymer polyethylene pads between the prosthesis group and the control group specimens.
Conclusions
Ni-Ti memory alloy metacarpophalangeal joint prosthesis conforms to the biomechanical characteristics of metacarpophalangeal joints without implants, and the fatigue strength can fully meet the needs of metacarpophalangeal joint activities after joint replacement.
OBJECTIVETo investigate standard modifiable cardiovascular risk factors (SMuRFs) and prognosis of patients with acute coronary syndrome (ACS) aged 50 years or younger. STUDY DESIGNAn observational ...study. PLACE AND DURATION OF STUDYEleven general hospitals in Chengdu, Sichuan Province, China, from January 2017 to June 2019. METHODOLOGYPatients with ACS were stratified into younger group (≤50 years) and older group (>50 years). The baseline characteristics and prognosis were compared for two groups. Survival analysis was used to assess the long-term prognosis. RESULTSAmong a total of 1982 ACS patients, 322 (16.2%) were of ≤50 years. Compared with older patients, younger patients were more likely to have at least one SMuRFs (90.0% vs. 84.3%, p=0.013). The younger group had a higher prevalence of smoking (62.8% vs. 34.1%, p <0.001) and hypercholesterolemia (36.2% vs. 23.4%, p <0.001) compared with the older group. Younger male patients were more likely to have at least one SMuRFs than younger female patients (91.6% vs. 74.1%, p = 0.011). After the follow-up of 15 (10, 22) months, the cumulative rates of major adverse cardiovascular and cerebrovascular events (MACCE) of the younger patients were significantly lower than those in the older patients hazard ratio (HR): 0.2661, 95% confidence interval (CI): 0.1932 - 0.3665, p <0.001. CONCLUSIONYounger patients with ACS were more likely to have at least one SMuRFs; and were likely to have a better prognosis than older patients. Key Words: Coronary artery disease, Acute coronary syndrome, Middle aged, Risk factors, Prognosis.
Syphilis, a chronic multisystemic disease caused by spirochete
subspecies
infection, continues to be a serious global health problem and congenital syphilis remains a major cause of adverse outcomes ...in pregnancy in developing countries. The development of an effective vaccine is the most cost-effective way to eliminate syphilis, but so far has been elusive. Here, we evaluated the immunogenicity and protective efficacy of Tp0954, a
placental adhesin, as a potential vaccine candidate in a New Zealand White rabbit model of experimental syphilis. Animals immunized with recombinant Tp0954 (rTp0954) produced high titers of Tp0954-specific serum IgG, high levels of IFN-γ from splenocytes and specific splenocyte proliferation response when compared to control animals immunized with PBS and Freund's adjuvant (FA). Furthermore, rTp0954 immunization significantly delayed the development of cutaneous lesions, promoted inflammatory cellular infiltration at the primary lesion sites, as well as inhibited
dissemination to distal tissues or organs when compared with that of the control animals. In addition, the naïve rabbits receiving popliteal lymph nodes from Tp0954-immunized,
-challenged animals were not infected by
, confirming sterile immunity. These findings suggest that Tp0954 is a potential vaccine candidate against syphilis.
A novel approach using metabolomics coupled with a metabolic network was used to investigate the effects of Tao‐Hong‐Si‐Wu decoction (THSWD) on the rat model of acute blood stasis syndrome. Acute ...blood stasis syndrome was induced by placing the rats in ice‐cold water following two injections with epinephrine. The hemorheological indicators whole blood viscosity (WBV) and plasma viscosity (PV) and the blood coagulation indicators thrombin time (TT), prothrombin time (PT), activated partial thromboplastin time (APTT) and fibrinogen (FIB) were detected. The nonparametric univariate method and multivariate statistical analysis were performed for determining the potential biomarkers. A correlation map was structured between biochemical indicators and hub metabolites to explain the effects mechanism of THSWD. After the administration of THSWD, the levels of WBV, PV, TT, APTT and FIB returned to levels observed in the control group. According to metabolomics coupled with metabolic network analysis, the intervention of THSWD in rats with acute blood stasis syndrome induced substantial and characteristic changes in their metabolic profiles. Fifteen metabolites were screened, which mainly involved 10 pathways and five hub metabolites, namely, l‐glutamate, l‐phenylalanine, N‐acylsphingosine, arachidonic acid and phosphatidate. The biochemical indicators and hub metabolites could be adjusted to close to normal levels by THSWD. Therefore, combining metabolomics and metabolic network helped to evaluate the effects of THSWD on acute blood stasis.
Whether lipoprotein(a) Lp(a) is associated with recurrent cardiovascular events (RCVEs) still remains controversial. The present study aimed to investigate the prognostic value of Lp(a) for long-term ...RCVEs and each component of it in people with acute coronary syndrome (ACS).
This multicenter, observational and retrospective study enrolled 765 ACS patients at 11 hospitals in Chengdu from January 2014 to June 2019. Patients were assigned to low-Lp(a) group Lp(a) < 30 mg/dl and high-Lp(a) group Lp(a) ≥ 30 mg/dl. The primary and secondary endpoints were defined as RCVEs and their elements, including all-cause death, nonfatal myocardial infarction (MI), nonfatal stroke and unplanned revascularization.
Over a median 17-month follow-up, 113 (14.8%) patients presented with RCVEs were reported, among which we observed 57 (7.5%) all-cause deaths, 22 (2.9%) cases of nonfatal stroke, 13 (1.7%) cases of nonfatal MI and 33 (4.3%) cases of unplanned revascularization. The incidences of RCVEs and revascularization in the high-Lp(a) group were significantly higher than those in the low-Lp(a) group (P < 0.05), whereas rates of all-cause death, nonfatal stroke and nonfatal MI were not statistically different (P > 0.05). Kaplan-Meier analysis also revealed the same trend. Multivariate Cox proportional hazards analysis showed that 1-SD increase of Lp(a) was independently associated with both the primary endpoint event hazard ratio (HR), 1.285 per 1-SD; 95% confidence interval (CI), 1.112-1.484; P < 0.001 and revascularization (HR, 1.588 per 1-SD; 95% CI, 1.305-1.932; P < 0.001), but not with the other secondary events.
Increased Lp(a) is an independent predictor of RCVEs and unplanned revascularization in patients with ACS.
Development of biocompatible and biodegradable 3D scaffold for biomedical application has been challenging. Herein, the application of a novel nanocomposite 3D scaffold based on poly vinyl alcohol ...and sodium alginate embedded with Ca2+ doped titanium dioxide nanoparticle (PVA+SA/Ca@TiO2) as bioactive material was investigated. The 3D scaffold was prepared using a solvent casting method and characterized using FTIR, SEM, XRD and TGA to study their physiochemical properties. The spectroscopy techniques were used to confirm the formation of the required poly vinyl alcohol and sodium alginate with Ca doped TiO2 nanoparticles fillers interaction by the identification of bands. The Ti-OH bonds and the bonds related to the interconnected network between the inorganic and the organic components from hybrids. The PVA+SA/Ca@TiO2 nanocomposite 3D scaffold was demonstrated good bioactivity to promote nucleation and growth of hydroxyapatite (HAp) in the simulated body fluid. The PVA+SA/Ca@TiO2 nanocomposite 3D scaffold supported the growth and proliferation of 3T3 mouse fibroblast cells with strong proliferation and cell attachment. The biocompatibility and nontoxic character of the 3D scaffold was probed using fibroblast cell with over 90% of cell viability. It offers a potential for cell attachment and captured for biomedical application.
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