Adult ; Aged ; China/epidemiology* ; Cohort Studies ; Female ; Humans ; Male ; Metabolic Syndrome/etiology* ; Middle Aged ; Parks, Recreational/supply & distribution* ; Prevalence ; Residence Characteristics/statistics & numerical data* ; Rural Population/statistics & numerical data* ; Young Adult

Objective: Based on the Mendelian randomization analysis, to assess the causal relationship between DNA methylation levels of Janus kinase 2 (JAK2) and obesity. Methods: A case-control study was carried out, including 1 021 individuals [obesity (visceral fat index ≥10) vs. no obesity (visceral fat index <10) was 440 vs. 581] from the Henan Rural Cohort Study. MethylTarget^TM target region methylation sequencing technology was used for testing the DNA methylation level of JAK2. logistic regression models were used to assess the association between the DNA methylation level of JAK2 and obesity. With SNP as the instrumental variable, the association between the DNA methylation level of JAK2 and obesity was explored by using the Mendelian randomization analysis method. Results: There was a positive association between Chr9:4984943 (one DNA methylation site in the promoter of JAK2) and obesity, and the OR (95%CI) was 1.22(1.04-1.42). Methylation level of five sites in the exon of JAK2 (Chr9:4985378, Chr9:4985404, Chr9:4985407, Chr9:4985409 and Chr9:4985435) were negatively associated with obesity, the corresponding OR (95%CI) were 0.53 (0.29-0.95), 0.58(0.36-0.93), 0.69 (0.49-0.97), 0.72 (0.53-0.99) and 0.58 (0.35-0.98) , respectively. Mendelian randomization analysis showed that there was a causal relationship between the DNA methylation levels of JAK2 and obesity, and the corresponding β (95%CI) were -1.985 (-3.520 - -0.450),-3.547 (-6.301 - -0.792) and -3.900 (-6.328 - -1.472) for Mendelian randomization method of inverse variance weighted, Mendelian randomization method of median based and Maximum-likelihood method, respectively. Conclusion: This study supported there was a causal relationship between the DNA methylation level of JAK2 and obesity.
Case-Control Studies ; Cohort Studies ; DNA Methylation ; Genome-Wide Association Study ; Humans ; Janus Kinase 2/genetics* ; Mendelian Randomization Analysis/methods* ; Obesity/genetics* ; Polymorphism, Single Nucleotide

As the body ages， the immune system will undergo a series of changes， which are termed "immunosenescence" and are embodied in immune cells. Previous studies have shown that the immune cells involved in the regulation of immunosenescence include intrinsic immune cells and adaptive immune cells. Intrinsic immune cells are neutrophils， monocytes/macrophages， myeloid-derived suppressor cells， dendritic cells， natural killer cells， etc.， and the underlying mechanisms involve the regulation of cell number， phagocytosis， chemotaxis， adhesion， the function of toll-like receptor （TLR）， antigen presentation， macrophage polarization， cytotoxicity， migration， etc. The adaptive immune cells include T-lymphocytes and B-lymphocytes， and the underlying mechanisms involve the regulation of cell development， proliferation， differentiation， cell number， telomerase activity， self-reactive antibodies， etc. Immunosenescence is the manifestation of aging in the human body and is also an important target for delaying aging by Chinese medicine and western medicine. In recent years， scholars have found some classical prescriptions and their active components （such as Dushentang and total saponins in Panax ginseng leaves， and Shengmaiyin and anwulignan and total saponins in P. ginseng stems and leaves） can regulate immunosenescence by targeting the immune cells and interfering with their molecular regulatory mechanisms. In addition， the mechanisms of the classical prescriptions in regulating immunosenescence are closely related to autophagy. The representative prescription embodying the therapeutic principles of resolving blood stasis and promoting regeneration， Dahuang Zhechongwan， can delay D-galactose-induced renal aging in mice， and its underlying mechanisms are related to the regulation of the number and activity of thymic immune cells and improvement of the protein expression of autophagy-related markers and inflammatory cytokines in the kidney. Therefore， exploring the effects of the classical prescriptions and their active components by targeting the mechanisms of immunosenescence will become a new direction for investigating and developing anti-aging drugs.

Fucoidan(FPS) is an effective component of the Chinese patent medicine named Haikun Shenxi, which treats schronic renal failure in clinics, and has the potential anti-aging effects. However, it is still unclear whether FPS can improve renal aging, especially the molecular mechanism of its anti-aging. The human proximal renal tubular epithelial cells(HK-2) in vitro were divided into normal group(N), D-gal model group(D), low dose of FPS group(L-FPS), high dose of FPS group(H-FPS) and vitamin E group(VE), and treated by the different measures, respectively. More specifically, the HK-2 cells in each group were separately treated by 1 mL of 1% fetal bovine serum(FBS) or D-galactose(D-gal, 75 mmol·L~(-1)) or D-gal(75 mmol·L~(-1))+FPS(25 μg·mL~(-1)) or D-gal(75 mmol·L~(-1))+FPS(50 μg·mL~(-1)) or D-gal(75 mmol·L~(-1))+VE(50 μg·mL~(-1)). After the treatment for 24 h, firstly, the effects of D-gal on senescence-associated β-galactosidase(SA-β-gal) staining characteristics and klotho, P53 and P21 protein expression le-vels, as well as adenosine monophosphate activated protein kinase(AMPK)-uncoordinated 51-like kinase 1(ULK1) signaling pathway activation in the HK-2 cells were detected, respectively. Secondly, the effects of FPS and VE on SA-β-gal staining characteristics and klotho, P53 and P21 protein expression levels in the HK-2 cells exposed to D-gal were investigated, respectively. Finally, the effects of FPS and VE on microtubule-associated protein 1 light chain 3(LC3) protein expression level and AMPK-ULK1 signaling pathway activation in the HK-2 cells exposed to D-gal were examined severally. The results indicated that, for the HK-2 cells, the dose of 75 mmol·L~(-1) D-gal could induce the changes of SA-β-gal staining characteristics and klotho, P53 and P21 protein expression levels. That is causing cells aging. FPS and VE could both ameliorate the changes of SA-β-gal staining characteristics and klotho, P53 and P21 protein expression levels in the HK-2 cells exposed to D-gal. That is anti-cells aging, here, the functions of FPS and VE are similar. D-gal could not only induce cell aging but also increase LC3Ⅱ, phosphorylated-AMPK(p-AMPK) and phosphorylated-ULK1(p-ULK1) protein expressions, and activate autophagy-related AMPK-ULK1 signaling pathway. FPS and VE could both improve the changes of LC3Ⅱ, p-AMPK and p-ULK1 protein expression levels in the HK-2 cells exposed to D-gal. That is inhibiting autophagy-related AMPK-ULK1 signaling pathway activation. On the whole, for the human proximal renal tubular epithelial cells aging models induced by D-gal, FPS similar to VE, can ameliorate renal cells aging by possibly inhibiting autophagy-related AMPK-ULK1 signaling pathway activation. This finding provides the preliminary pharmacologic evidences for FPS protecting against renal aging.
Aging ; Autophagy ; Epithelial Cells ; Humans ; Polysaccharides ; Signal Transduction

Characteristics of collapsed tibial plateau fracture determines that the joint surface must remain anatomical reduction,line of force in tibial must exist and internal fixation must be strong. However, while renewing articular surface smoothness, surgeons have a lot of problems in dealing with bone defect under the joint surface. Current materials used for bone defect treatment include three categories: autologous bone, allograft bone and bone substitutes. Some scholars think that autologous bone grafts have a number of drawbacks, such as increasing trauma, prolonged operation time, the limited source, bone area bleeding,continuous pain, local infection and anesthesia,but most scholars believe that the autologous cancellous bone graft is still the golden standard. Allograft bone has the ability of bone conduction, but the existence of immune responses, the possibility of a virus infection, and the limited source of the allograft cannot meet the clinical demands. Likewise, bone substitutes have the problem that osteogenesis does not match with degradation in rates. Clinical doctors can meet the demand of the patient's bone graft according to patient's own situation and economic conditions.
Bone Substitutes ; Bone Transplantation ; Humans ; Tibial Fractures ; surgery

OBJECTIVETo summarize clinical outcomes of locking compression plate (LCP) combined with minimally invasive percutaneous plate osteosynthesis (MIPPO) for the treatment of Pilon fracture.

METHODSFrom January 2009 to December 2012, Pilon fracture patients treated by LCP with MIPPO were retrospectively analyzed. All open fractures, pathologic fractures and those who had limb vascular disease or nerve injury were excluded. Thirty-eight patients were enrolled, including 29 males and 9 females aged from 21 to 78 years old with an average of 48 years old. According to AO classification, 20 cases were type B, 18 cases were type C. Operative time, blood loss, reduction quality, time of fracture healing complications and postoperative ankle joint function were applied for evaluating clinical outcomes, AOFAS scoring were used for assessing postoperative clinical effects.

RESULTSAll patients were followed up from 13 to 24 months (averaged 18 months). All patients obtained bone union without any plate failures or loss of fixation/reduction. One patient occurred superficial wound infection, and resolved with antibiotics and local wound care. Postoperative average AOFAS score was 81 (ranged 65 to 97).

CONCLUSIONLCP with MIPPO for Pilon fratcure has advantages of less invasion, fewer complications and satisfactory ankle function.

Adult ; Aged ; Bone Plates ; Female ; Fracture Fixation, Internal ; methods ; Humans ; Male ; Middle Aged ; Minimally Invasive Surgical Procedures ; methods ; Retrospective Studies ; Tibial Fractures ; surgery

OBJECTIVETo study the related risk factors for surgical site infection following Pilon fracture surgery. METH ODS: The data of 561 patients with Pilon fractures treated with open reduction plate osteosynthesis at our institution's trauma centre were collected from January 2006 to December 2012. All the patients were divided into two groups: infection group and non-infection group. In the infection group, there were 23 males and 10 females, ranging in age from 21 to 69 years old, with an average of (45.50±4.40) years old. In the non-infection group, there were 296 males and 232 females, ranging in age from 16 to 76 years old, with an average of (43.50±7.19) years old. The possible risk factors such as age, gender, smoking, diabetes, alcohol abuse, open fractures, compartment syndrome and operative time were studied. The multivariate Logistic regression model was used to analyze the risk, factors.

RESULTSThe infection rate of surgical site after Pilon fracture surgery was 5.88%. There were significant statistical differences between infection group and non-infection group in operative time, open fractures and compartment syndrome. However, multivariate Logistic regression analysis revealed that only operative time was significantly associated with surgical site infection (P=0.005, OR=44.92).

CONCLUSIONOperation time is an independent predictor for post-operative surgical site infection of Pilon fracture treated with open reduction plate osteosynthesis. Though open fracture and compartment syndrome could increase the surgical site infection rate, they could not not be considered as independent predictors.

Adult ; Compartment Syndromes ; complications ; Female ; Humans ; Logistic Models ; Male ; Middle Aged ; Operative Time ; Risk Factors ; Surgical Wound Infection ; etiology ; Tibial Fractures ; surgery

OBJECTIVETo analyze the early clinical and radiographic outcomes of Hoffa fractures treated by a standard protocol of open reduction and internal fixation using headless compression screws combined with back buttress plate in a consecutive series of 8 Chinese patients.

METHODSOpen reduction and internal fixation was performed on all patients. The fractures were anatomically reduced and held temporarily by K-wire. If the ends of fractures were atrophic, autologous bone graft from the ipsilateral iliac crest was packed between the ends. Then the fracture fragments were fixed with AO 6.5 mm headless compression cannulated screws. At least two screws were used to provide rotational stability. One pre-contoured reconstruction plate was placed on the nonarticular surface posteromedially or posterolaterally as back buttress plate.

RESULTSAll the patients were followed up for at least 12 months (range 12-25 months). All fractures achieved anatomical reduction and healed clinically and radiographically. At recent follow-up, the mean flexion degree was 120.6° (range 110°-135°) and the mean extension degree was 2.5° (range 0°-5°). The average visual analogue scale score was 1.6 points (range 0-3). Six patients were assessed as excellent and 2 as good according to the hospital for special surgery knee score system. There were no superficial or deep infections, or hardware breakages. No patient had giving way or locking of the knee, though some had intermittent pain and swelling after strenuous exercise. Injury mechanism had significant influence on the functional outcome (P=0.046).

CONCLUSIONHeadless compression screws combined with back buttress plate and/or autologous bone grafting to treat old Hoffa fracture is one of effective measures. It would be conducive to not only fracture healing but also early exercise and functional recovery.

Adult ; Bone Plates ; Bone Screws ; Female ; Femoral Fractures ; surgery ; Fracture Fixation, Internal ; methods ; Humans ; Male ; Middle Aged

OBJECTIVETo explore the clinical effects of anterior decompression and fusion with a nano-hydroxyapatite/ polyamide 66 (n-HA/PA66) cage in treating lower cervical fracture and dislocation.

METHODSFrom January 2008 to December 2010, the clinical data of 42 patients with lower cervical fracture and dislocation were retrospectively analyzed. There were 29 males and 13 females aged from 20 to 65 years old. The mean age was 46.8 years. Five cases got injuried in C3, 14 cases in C4, 12 cases in C5, 7 cases in C6 and 4 cases in C7. According to Frankel grade, 4 cases were classified in grade A, 11 cases in grade B, 13 cases in grade C, 9 cases in grade D and 5 cases in grade F. Twenty-eight cases were treated with anterior corpectomy and fusion and 14 cases with anterior discectomy and fusion. Frankel grade was used to do neurologic assessment and visual analogue scale (VAS) was used to evaluate the improvement of clinical symptoms. Segmental height and sagittal lordosis were measured by radiographs and cage location. Cage appearance and fusion status were assessed by 3D-CT images.

RESULTSAll patients were followed up for 3 to 5.2 years with an average of 4.1 years. Frankel grade had obviously improved than preoperative (Z = -4.845, P < 0.001). There were 2, 3, 11, 8, 11 cases classified in grade A, grade B, grade C, grade D and grade E respectively. At the third day after operation and latest follow-up,VAS was (2.6 +/- 1.8),(1.3 +/- 1.0) scores respectively. Both had improved than preoperative (P < 0.05). Up to the latest follow-up, there was only one patient (2.4%) with slight cage translocation (less than 2 mm), however, no cage prolapsed, or collapse, or breakage were found. Both segmental height and lordosis improved significantly after surgery (P < 0.001). And there was not significant difference in both parameters between each postoperative time points (P > 0.05). The mean distance of cage subsidence was 1.5 mm and the rate of cage subsidence (> 3 mm) was 4.8%.

CONCLUSIONThe n-HA/PA66 cage can not only restore and maintain the fusion segmental height and radian, but also promote the osseous fusion and profit the radiographic assessment after operation. Thus, it was an ideal material for prop graft.

Adult ; Aged ; Cervical Vertebrae ; injuries ; surgery ; Decompression, Surgical ; methods ; Female ; Humans ; Joint Dislocations ; surgery ; Male ; Middle Aged ; Retrospective Studies ; Spinal Fractures ; surgery ; Spinal Fusion ; methods

OBJECTIVETo investigate the effects of benzo[a]pyrene (B[a]P) exposure on the behaviors and hippocampal oxidative stress and ATPase in rats and the molecular mechanism of neurobehavioral toxicity of B[a]P.

METHODSA total of 120 male SD rats (21 days old) were randomly and equally assigned to five groups: blank control group, vegetable oil (solvent control) group, and 2.5, 5, and 10 mg/kg B[a]P exposure groups. The rats in B[a]P exposure groups were injected intraperitoneally with B[a]P once a day for 4 consecutive weeks. Then, Morris water maze and shuttle box were used to evaluate the learning and memory abilities of rats; colorimetric assay was used to measure the activities of superoxide dismutase (SOD), Na(+)/K(+)-ATPase, and Ca(2+)/Mg(2+)-ATPase and the content of malonaldehyde (MDA) in the hippocampus; the concentration of Ca(2+) in the hippocampus was measured by fluorescent labeling.

RESULTSCompared with the blank control group and solvent control group, the B[a]P exposure groups exhibited significant increases in escape latency, active avoidance response latency, and passive avoidance response latency and significant decreases in number of platform crossings and active avoidance response frequency in the last test (P < 0.05 for all comparisons), with a dose-effect relationship. In addition, the B[a]P exposure groups had significantly lower activities of SOD, Na(+)/K(+)-AT-Pase, and Ca(2+)/Mg(2+)-ATPase and significantly higher MDA level and Ca(2+) concentration than the blank control group and solvent control group (P < 0.05 for all comparisons), with a dose-effect relationship.

CONCLUSIONThe neurobehavioral toxicity of B[a]P may be related to increased oxidative stress and decreased activities of Na(+)/K(+)-ATPase and Ca(2+)/Mg(2+)-ATPase in the hippocampus of rats.

Animals ; Benzo(a)pyrene ; toxicity ; Ca(2+) Mg(2+)-ATPase ; metabolism ; Hippocampus ; drug effects ; metabolism ; Male ; Oxidative Stress ; drug effects ; Rats ; Rats, Sprague-Dawley ; Sodium-Potassium-Exchanging ATPase ; metabolism ; Superoxide Dismutase ; metabolism