BACKGROUND: Mainly pathological changes of Parkinson disease (PD)are related to irreversible degeneration and reduction of dopamine neurons of substantia nigra in midbrain; however, oxidative stress reaction plays an important role in onset of PD. 3-nitropropionie acid (3-NP) is an inhibitor of mitochondria compound I, and it can inhibit oxidative phosphorylation so as to restrain energy metabolism. However, professor Riepe from Germany found that small dose of 3-NP can increase the tolerance of neurons to ischemic hypoxia. It is unclear whether it can also strengthen the tolerance of dopamine neurons to neurotoxin.OBJECTIVE: To investigate the possible mechanism and prevention of repetitively preconditioning 3-NP for treating PD.DESIGN: Controlled observational animal study. SETTING: Department of Neurology, Union Hospital affiliated to TongjiMedical College, Huazhong University of Science and Technology. MATERIALS: The experiment was carried out at the Neurological Lab oratory, Union Hospital affiliated to Tongji Medical College, Huazhong U niversity of Science and Technology from March to July 2004. A total of48 C57BL mice, weighing 18-20 g, aged 2-3 months, of both genders, were randomly divided into 6 groups with 8 in each group. ① Blank con trol group: Mice were not medicated. ② 3-NP single administrationgroup: Mice were intraperitoneally injected with 3-NP once. ③ 3-NPrepetitively administrations group: Mice were intraperitoneally injectedwith 3-NP every 5 days for 5 times in total. ④ Neurotoxin group: Micewere intraperitoneally injected with neurotoxin once every day for 5 timesin total. ⑤ 3-NP single preconditioning group: Mice were intraperitoneal ly injected with 3-NP once, and 3 days later, they were intraperitoneallyinjected with neurotoxin once every day for 5 times in total. ⑥ 3-NPrepetitively preconditionings group: Mice were intraperitoneally injectedwith 3-NP and repetitively every 5 days for 5 times in total; 3 days later, mice were intraperitoneally injected with neurotoxin once every day for5 times in total. Dosages of 3-NP and neurotoxin were 20 mg/kg and30 mg/kg, respectively. METHODS: Motor coordination of mice was scored with pole test andtraction test before experiment and at 3 days after the last injection ofneurotoxin. Three days after complete injection, mice were sacrificed rapid ly to measure the contents of malondialdehyde (MDA) and reduced glu tathione (GSH) in the substantia nigra of midbrain. MAIN OUTCOME MEASURES: ① Motor and behavior scores; ② con tent of MDA; ③ content of GSH.~ULTS: All 48 mice were involved in the final analysis. ① Scores of pole test and traction test were decreased in neurotoxin group as compared with those in control group (P＜0.01); but the scores were increased after 3-NP single/repetitively preconditionings, and there were significant difference (P＜0.05, P＜0.01). Meanwhile, there was also significant differencebetween 3-NP repetitively preconditionings group and 3-NP single preconditioning group (P＜0.05). ② Content of MDA was increased in neurotoxin group as compared with that in control group, and there was significant difference (P＜0.01); content of MDA was decreased after 3-NP single preconditioning as compared with that in neurotoxin group, and there was significant difference (P＜0.05); content of MDA was remarkably decreased after 3-NP repetitively preconditionings as compared with that in neurotoxin group, and there was greatly significant difference (P＜0.01); meanwhile, there was also significant difference between 3-NP repetitively preconditionings group and 3-NP single preconditioning group (P＜0.05). ③As compared with that in blank control group, content GSH in 3-NP single administration group was not changed; content of GSH in 3-NP repetitively administrations group was increased (P＜0.05); content of GSH in neurotoxin group was decreased as compared with that in blank control group (P＜0.01); content of GSH in 3-NP single preconditioning group was not changed as compared with that in neurotoxin group (P＞0.05); content of GSH was increased after 3-NP repetitively preconditionings, and there was significant difference (P＜0.05); meanwhile, there was significant difference between 3-NP repetitively preconditionings group and 3-NP single preconditioning group (P＜0.05).CONCLUSION: 3-NP repetitively preconditionings can activate synthesis of GSH, protect dopamine neurons through decreasing production of MDA.

This study examined the ability of 1,2,3,4,6-penta-O-galloyl-β-D-glucose (β-PGG) to induce the expression of heme oxygenase-1 (HO-1) in the PC12 cells and its regulation in the PC12 cells. One week before treatment with the drug, nerve growth factor (NGF) was added to the cultures at a final concentration of 50 ng/mL to induce neuronal differentiation. After drug treatment, HO-1 gene transcription was analyzed by reverse transcription polymerase chain reaction (RT-PCR). Expression of HO-1 and NF-E2-related factor2 (Nrf2) and activation of extracellular signal-regulated kinase (ERK) and Akt were detected by Western blotting. The viability of the PC12 cells treated with different medicines was examined by MTT assay. The oxidative stress in the PC12 cells was evaluated qualitatively and quantitatively by DCFH-DA. The results showed that β-PGG up-regulated HO-1 expression and this increased expression provided neuroprotection against MPP(+)-induced oxidative injury. Moreover, β-PGG induced Nrf2 nuclear translocation, which was found to be upstream of β-PGG-induced HO-1 expression, and the activation of ERK and Akt, a pathway that is involved in β-PGG-induced Nrf2 nuclear translocation, HO-1 expression and neuroprotection. In conclusion, β-PGG up-regulates HO-1 expression by stimulating Nrf2 nuclear translocation in an ERK- and Akt-dependent manner, and HO-1 expression by β-PGG may provide the PC12 cells with an acquired antioxidant defense capacity to survive the oxidative stress.

This study examined the ability of 1,2,3,4,6-penta-O-galloyl-β-D-glucose (β-PGG) to induce the expression of heme oxygenase-1 (HO-1) in the PC12 cells and its regulation in the PC12 cells. One week before treatment with the drug, nerve growth factor (NGF) was added to the cultures at a final concentration of 50 ng/mL to induce neuronal differentiation. After drug treatment, HO-1 gene transcription was analyzed by reverse transcription polymerase chain reaction (RT-PCR). Expression of HO-1 and NF-E2-related factor2 (Nrf2) and activation of extracellular signal-regulated kinase (ERK) and Akt were detected by Western blotting. The viability of the PC12 cells treated with different medicines was examined by MTT assay. The oxidative stress in the PC12 cells was evaluated qualitatively and quantitatively by DCFH-DA. The results showed that β-PGG up-regulated HO-1 expression and this increased expression provided neuroprotection against MPP(+)-induced oxidative injury. Moreover, β-PGG induced Nrf2 nuclear translocation, which was found to be upstream of β-PGG-induced HO-1 expression, and the activation of ERK and Akt, a pathway that is involved in β-PGG-induced Nrf2 nuclear translocation, HO-1 expression and neuroprotection. In conclusion, β-PGG up-regulates HO-1 expression by stimulating Nrf2 nuclear translocation in an ERK- and Akt-dependent manner, and HO-1 expression by β-PGG may provide the PC12 cells with an acquired antioxidant defense capacity to survive the oxidative stress.
Animals ; Cell Death ; drug effects ; genetics ; Cell Line, Tumor ; Heme Oxygenase-1 ; genetics ; Hydrolyzable Tannins ; pharmacology ; MAP Kinase Signaling System ; drug effects ; genetics ; PC12 Cells ; Piperidines ; adverse effects ; Proto-Oncogene Proteins c-akt ; genetics ; Pyrazoles ; adverse effects ; Rats

Objective To evaluate the clinical efficacy and safety of short-segment pedicle screw fixation combined with vertebroplasty for the treatment of thoracolumbar osteoporotic compression fractures.Methods A retrospective case control study was conducted on 63 patients with fresh thoracic or lumbar osteoporotie compression fractures who were surgically treated from January 2010 to December 2013.There were 26 males and 37 females,with age of 63-87 years [(76.3 ± 5.7) years].According to the surgical method,the patients were assigned to simple vertebroplasty group (Group A),short-segment pedicle screw fixation group (Group B),and short-segment pedicle screw fixation group combined with vertebroplasty group (Group C),with 21 cases in each group.Length of hospital stay,operation time,and blood loss were recorded.The visual analog scale (VAS),anterior vertebral body height,angle of the kyphotic deformity,and complications before operation,immediately after operation,3 months after operation,and at the last follow up were compared among three groups.Complications of each group were recorded.Results The hospital stay,operation time,and blood loss in Group C were significantly higher than those in Group A (P ＜ 0.05),but there were no significant differences between Group B and Group C (P ＞ 0.05),except for a longer operation time in Group C.The pre-operative VAS showed no significant difference among three groups (P ＞ 0.05).However,the mean VAS in Groups A,B and C at the last follow up were 1.0(0.0,2.0)points,1.0(0.0,2.0)points,0.0(0.0,1.0)points,respectively.The VAS in Group C was significantly lower than that in Group B or A (P ＜ 0.05).The mean anterior vertebral body height and angle of the kyphotic deformity in Group C had no significant difference from that in Group A or B before operation and immediately after operation (P ＞ 0.05).At the last follow up,the mean anterior vertebral body height and angle of the kyphotic deformity in Groups A,B and C were (68 ±14.7)％,(72.3 ±9.0)％,(81.5 ±5.6)％ and (10.6 ±3.9)°,(10.7 ±5.0)°,(7.4 ± 5.0) °,respectively.The loss of anterior vertebral body height and angle of the kyphotic deformity correction in Group C were significantly less than that in Group A or B (P ＜ 0.05).Superficial infection was found in Groups B (n =2) and C (n =1),and the infection was cured after antibiotic therapy and dress change.Bone cement leakage was found in Groups A (n =8) and C (n =5),with no nerve compression.Internal fixation failure was seen in Group B (n =3),and the implant was removed directly.Conclusion Short-segment pedicle screw fixation combined with vertebroplasty can effectively reduce the loss of anterior vertebral body height and angle of the kyphotic deformity and hence enhance the clinical efficacy.

Objective:To evaluate the efficacy of anteromedial extensile approach in the treatment of complicated closed pilon fractures classified as type AO/OTA C2 or C3 . Methods:Twenty‐three patients ,who suffered from complicated closed pilon fractures of distal tibia(25 lesions) ,underwent open reduction and internal fixation with anteromedial extensile approach . Among the 23 patients , there were 18 males and 5 females , with mean age of (43 .7 ± 9 .0 ) years . According to AO classification ,there were 11 lesions of type C2 and 14 lesions of type C3 .Operating time ,blood loss ,time of fracture healing , situation of complications ,and American Orthopedic Foot&Ankle Society(AOFAS) score were recorded ,so as to analyze the safety ,the indication ,and the pros and cons of this approach . Results:The average operating time was (119 .6 ± 23 .6)min . The intraoperative blood loss was (168 ± 64 .4) mL .And the time of fracture healing was (12 .5 ± 5 .4)weeks .The AOFAS scores were 81 .9 ± 18 .2 and 79 .9 ± 19 .5 at 12 month and 24 month after surgery ,respectively .Four cases of complications were observed , and there was no patient with invalid internal fixation . Conclusion:During the surgical treatment of complicated closed pilon fractures ,the anteromedial extensile approach allows complete access to the medial and lateral column of distal tibia and the articular surface ,so that the incidence rate of soft tissue complications was low and the clinical efficacy was satisfactory .

Objective:To explore the accuracy of CT three dimensional reconstruction technique for the diagnosis of tibia shaft fracture accompanied by ankle injury .Methods:Both X‐ray examination and three dimensional CT scanning were conducted for the 117 patients with closed tibia shaft fracture ,who went to Zhongshan Hospital of Fudan University ,before surgery .The numbers of patients ,who were diagnosed with tibia shaft fracture accompanied by ankle injury ,were compared between the two examination methods .Results:Nineteen patients with tibia shaft fracture were diagnosed with accompanied posterior malleolar fracture by X‐ray examination before surgery . However ,34 patients were diagnosed with accompanied posterior malleolar fracture by CT three dimensional reconstruction images . Thus , 15 more patients were diagnosed by CT three dimensional reconstruction technique than that by X‐ray imaging .Conclusions:Comparing with X‐ray examination , three dimensional CT reconstruction technique could increase the diagnosis accuracy for posterior malleolar fracture associated with tibia shaft fracture and reduce the rate of missed diagnosis .

Objective:To perform a prospective cohort study to identify individual susceptibility of glucocorticoid (GC) -associated osteonecrosis of the femoral head (GA-ONFH) and their clinical and genetic risk factors. Methods:The present prospective cohort study enrolled patients who received their first GC therapy between July 2015 and January 2018 at Zhongshan Hospital. All patients did not receive any GC treatment before enrollment. Further, they planned to start GC treatment with the dose (equivalent prednisone) of ≥30 mg/d, lasted ≥3 weeks, or pulse dose ≥200 mg/d, lasted ≥3 d. Blood samples were collected before GC treatment to evaluate bone metabolism and its released factors. Hip MRI was performed at the 1st, 3rd, 6th, 12th and 24th month to diagnose GA-ONFH. All patients were followed-up for ≥2 years. The endpoint was regarded as diagnosis of GA-ONFH or completion of 2 years follow-up. Lasso regression was performed to determine which clinical features were associated with GA-ONFH. A nested case-control sub-cohort (A, n=12) was established prospectively based on the main cohort by 1∶1 matching. Whole exome sequencing was performed to screen differential and functional candidate single nucleotide polymorphisms and insertion-deletions (SNP/InDels). Another sub-cohort (B, n=50) was constructed retrospectively in patients with GA-ONFH and non-ONFH patients received standard high dose GC treatment for more than two years. The candidate SNP/InDels were verified by Sanger sequencing based on the patients from sub-cohort B. Results:A total of 96 patients were enrolled of which 88 of them (32 males and 56 females, mean age 42.30 years) completed follow-up. Eight cases (9.1%) were diagnosed with GA-ONFH. The median time from the start of GC therapy to the diagnosis of ONFH was 53.00(34.00,13.50) days. The baseline characteristics, such as age, sex and body mass index, indicated no significant difference between the ONFH group and the non-ONFH group. The cumulative GC dose of the ONFH patients in the first month was higher than that of non-ONFH [32.74(29.55, 47.05) mg/kg vs. 24.00(21.10, 29.45) mg/kg, Z=-2.410, P=0.016]. However, there was no significant difference of patients who underwent pulse therapy (37.5% vs. 10.0%, adjusted χ 2=2.829, P=0.093). The ratio of serum apolipoprotein B/apolipoprotein A1 (ApoB/ApoA1) in patients with ONFH was higher than that in non-ONFH group before GC use [0.95(0.80, 1.50) vs. 0.70(0.60, 0.80), Z=-2.875, P=0.000]. Due to the multicollinearity, Lasso regression model was performed to reduce overfitting. All variables were included in the model. The results suggested that higher ApoB/ApoA1 ratio, lower serum β-c-terminal telopeptide (β-CTX) and higher cumulative GC dose in the first month were the top three risk factors of GA-ONFH. This model had an accuracy of 0.982 in internal validation. Seven differential candidate SNP/InDels were found by whole exome sequencing of sub-cohort A. We further verified these SNP/InDels in sub-cohort B. The patients with COLEC12 mutation (rs2305027, G1816A) were at risk of GA-ONFH ( OR=6.00, 95% CI: 1.17, 30.73). Conclusion:Higher first-month GC dose, lower serum β-CTX level before treatment, higher ApoB/ApoA1 ratio and COLEC12 mutation (rs2305027, G1816A) could increase the risk of GA-ONFH.

Objective:To investigate the incidence of anemia and risk factors in HIV/AIDS patients with access to antiretroviral therapy (ART) during 2004-2018 in Dehong Jingpo and Dai Autonomous Prefecture (Dehong).Methods:A retrospective cohort study was conducted in HIV/AIDS patients receiving ART in Dehong during 2004-2018 based on the data extracted from the National HIV/AIDS antiretroviral therapy database. Cox proportional risk model was used to analyze the factors associated with the incidences of anemia and moderate or severe anemia in the HIV/AIDS patients. And the piecewise linear mixed-effects model was used to depict the trajectory of hemoglobin changes over time after initiating ART according to baseline level.Results:A total of 8 044 HIV/AIDS patients were included, in whom 6 337 (78.8%) were without anemia at baseline survey and had a median follow up time of 4.43 ( P 25, P 75: 1.50, 6.71) years. The median follow up time for 1 291 new anemia cases and 293 new moderate or severe anemia cases was 0.16 ( P 25, P 75: 0.07, 1.99) years and 0.48 ( P 25, P 75:0.09, 2.97) years, respectively. The incidence rate of anemia and moderate or severe anemia was 4.40 per 100 person-years and 0.41 per 100 person-years respectively. In multivariable Cox regression analysis, older age, being female, being in Dai and Jingpo ethnic group, baseline BMI <18.5 kg/m 2, baseline CD4 +T lymphocyte cell counts (CD4) <200 cells/μl, and zidovudine (AZT) -based initial treatment regimen were factors significantly and positively associated with incidence of anemia after treatment. Factors as being female, being in Dai ethnic group, baseline BMI <18.5 kg/m 2, mild baseline anemia, and AZT-based initial treatment regimen were significantly and positively associated with incidence of moderate or severe anemia after treatment. Conclusion:The risk for anemia was higher in HIV/AIDS patients with specific characteristics, such as age ≥60 years , being female, being in Dai and Jingpo ethnic groups, lower BMI, CD4 <200 cells/μl, and treatment of AZT, after initiation of ART in Dehong during 2004-2018. Additional efforts are needed to strengthen the screening, prevention and treatment of anemia in this population.

Objective:To understand the incidence of diabetes and influencing factors, the trend of FPG change and risk for mortality in HIV-infected individuals after antiretroviral therapy (ART) in Dehong Dai and Jingpo Autonomous Prefecture (Dehong).Methods:The HIV/AIDS treatment database was collected from China Information System for Disease Control and Prevention. This retrospective cohort study was conducted in HIV-infected individuals with access to ART in Dehong during 2004-2020.The Cox proportional hazard regression model was used to analyze the incidence density of diabetes, the influencing factors and risk for mortality in HIV-infected individuals with access to ART, mixed linear effects model was used to analyze the trend of FPG change and predict FPG in those with different glucose metabolic status at baseline survey. Statistical analysis was performed using software SAS 9.4.Results:A total of 8 763 HIV-infected individuals were included, in whom 8 432 (96.2%) had no diabetes, 331 had diabetes. The incidence density of diabetes was 2.31/1 000 person years. Multivariate Cox proportional hazard regression analysis revealed that 30- 59 years old, BMI ≥24.0 kg/m 2, Efavirenz (EFV) based initial treatment regimen and impaired fasting glucose (IFG) at baseline survey were significantly and positively associated with incidence of diabetes. Mixed effect model revealed that FPG was positively correlated with the duration of ART, age and baseline FPG. Suffering from diabetes was a risk factor for mortality in HIV-infected individuals both at baseline survey and during follow-up. Conclusions:The risk for diabetes increased in HIV-infected individuals who were 30-59 years old, baseline BMI ≥24.0 kg/m 2, received EFV based initial treatment, and IFG in HIV-infected individuals after antiretroviral therapy in Dehong, 2004-2020. It is important to pay close attention to their blood glucose, and patients with high blood glucose should receive treatment as early as possible.