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Cholesterol is an important precursor of many endogenous molecules. Disruption of cholesterol homeostasis can cause many pathological changes, leading to liver and cardiovascular diseases. CYP1A is widely involved in cholesterol metabolic network, but its exact function has not been fully elucidated. Here, we aim to explore how CYP1A regulates cholesterol homeostasis. Our data showed that CYP1A1/2 knockout (KO) rats presented cholesterol deposition in blood and liver. The serum levels of low-density lipoprotein cholesterol, high-density lipoprotein cholesterol and total cholesterol were significantly increased in KO rats. Further studies found that the lipogenesis pathway (LXRα-SREBP1-SCD1) of KO rats was activated, and the key protein of cholesterol ester hydrolysis (CES1) was inhibited. Importantly, lansoprazole can significantly alleviate rat hepatic lipid deposition in hypercholesterolemia models by inducing CYP1A. Our findings reveal the role of CYP1A as a potential regulator of cholesterol homeostasis and provide a new perspective for the treatment of hypercholesterolemia.
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The 2020 Nobel Prize in Chemistry recognized CRISPR-Cas9, a super-selective and precise gene editing tool. CRISPR-Cas9 has an obvious advantage in editing multiple genes in the same cell, and presents great potential in disease treatment and animal model construction. In recent years, CRISPR-Cas9 has been used to establish a series of rat models of drug metabolism and pharmacokinetics (DMPK), such as
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The co-existence of different neurodegenerative diseases in the same case has received increasing attention and reports. A rare comorbidity of amyotrophic lateral sclerosis (ALS) and progressive supranuclear palsy (PSP) in a sporadic patient was reported. The patient presented with pseudobulbar palsy, freezing gait, and developed muscle weakness and fasciculation. Brain magnetic resonance imaging, positron emission computed tomography and whole exomesequencing showed no evident abnormality. The patient had no response towards the treatment of levodopa, and received supportive treatment and gastrostomy. He is in stable condition by now. Totally 23 cases of ALS with PSP were reviewed, and found that the clinical manifestations were related to the main distribution of pathological inclusion bodies and the location of neuron loss, and the deposition of the same pathological protein in multiple systems may lead to the coexistence of different neurodegenerative diseases. Traditional treatment is generally ineffective, thus support treatment is pivotal. The genetic background and pathogenesis of this comorbidity should be studied in the future.
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Objective To study the clinical efficacy and safety of posterior laminoplasty combined with foraminotomy in the treatment of mixed cervical spondylosis.Methods A total of 70 patients with mixed type cervical spondylosis from January 2012 to January 2014 in our hospital were randomly divided into observation group and control group.Patients in observation group received posterior laminoplasty com-bined with foraminotomy,and patients in control group received anterior cervical discectomy and fusion surgery.The operation time,intraoper-ative blood lossing,postoperative JOA scores and NDI scores between two groups were compared.The cervical curvature and range of motion were measured by X-ray.Results There was no significant difference in postoperative JOA scores,cervical curvature and range of motion be-tween two groups(P >0.05).The operative time and intraoperative blood loss of observation group was less than those of control group,the difference was no significance.The NDI scores of carrying and drive in observation group were higher than those in control group,while the NDI scores of other items between two groups had no significant difference(P >0.05).The incidence of complications in observation group was 10.81% (4 /37),the control group was 24.42% (8 /33),the difference between two groups was statistically significant,(χ2 =3.428, P <0.05).Conclusion The posterior laminoplasty combined with foraminotomy have good clinical effect for mixed type cervical spondylosis with advantages of a shorter operation time,simple operation,less intraoperative bleeding,lower incidence of complications,which is a kind of safe and effective surgical method.
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BACKGROUND:For vertebral compression fractures treated by bal oon vertebroplasty, there were stil controversies in biomechanical and clinical studies about adjacent vertebral fractures is the result of osteoporosis progress, or the result of vertebral intervention and strengthening by injecting bone cement. More accurate conclusions can be obtained through more in-depth research and long-term fol ow-up. OBJECTIVE:To evaluate the effect of bal oon vertebroplasty on biomechanical properties of vertebral body with compression fractures and unstrengthened adjacent vertebral body. METHODS:Total y 40 pig specimens with vertebral compression fractures were prepared and randomly divided into study and control groups. Specimens in the study group were subjected to bal oon vertebroplasty. Specimens in the control group only wrapped with normal saline gauze. The biomechanical properties (vertebral height, maximum load), stress, strain and displacement values of specimens under 500 N loading in these two groups were compared. The stress and strain values of unstrengthened adjacent vertebral body before and after the bal oon vertebroplasty in the study group were measured, and compared with the control group. RESULTS AND CONCLUSION:Compared with the original height, specimens in the study group can restore to its original height after bal oon vertebroplasty, the differences were not significant (P>0.05). The former, back, left and right vertebral height in the study group were significantly higher than those in the control group (P0.05). There were no significant differences in the strain and stress values of the unstrengthened adjacent vertebral body after the bal oon vertebroplasty between study group and control group (P>0.05). These results suggest that vertebral maximum loading and stiffness recover wel after the treatment of bal oon vertebroplasty for vertebral compression fractures, which can achieve the effect of preventing vertebral fractures again. Meanwhile, bal oon vertebroplasty treatment can not alter the biomechanical properties of adjacent vertebrae, and it is difficult to influence and lead vertebral fractures again, with a better security.
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Objective To investigate relationships between serum asymmetric dimethylarginine (ADMA) and transient ischemic attack (TIA).Methods Forty hcalthy controls and 40 patients with TIA were enrolled in the present study.ABCD2 score was used to evaluate risk for future stroke.Serum ADMA levels were measured with ELISA analysis.Results Serum level of ADMA was higher in TIA group than that in control group [(0.52 ± 0.06) mmol/L vs (0.23 ± 0.04) mmol/L,P ＜ 0.05].In TIA subgroup,19 cases(47.5％)developed cerebral infarction and 23 cases(57.5％)had no stroke history.There is positive correlation between serum ADMA levels and ABCD2 score in both cerebral infarction subjects (r =0.560,P =0.013),and no stroke history cases(r =0.602,P =0.002).TIA subjects were,then,divided in to two groups based on ABCD2 score as 0-3 group and ≥ 4 group.In general linear model analysis,ADMA level was associated with ABCD2 score (F =4.39,P =0.043) after adjusted for age and gender.This situation hold true for subjects within cerebral infarction group (F =7.327,P =0.017) or non-previous stroke group(F =12.300,P =0.002).No association could bc found between ADMA level and ABCD2 score grouping in subjects with non-infarct (F =0.523,P =0.675) or stroke history (F =0.274,P =0.609).Conclusions Elevated ADMA is associated with occurrence of TIA.Endothelial dysfunction may play an important role in the pathogenesis of TIA.
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Objective To explore the significance of proton magnetic resonance spectroscopy(1H- MRS)in patients with amyotrophic lateral sclerosis(ALS).Methods Single-voxel1 H-MRS was carried on the preeentral gyri in 110 patients with ALS and 24 patients with lower motor neuron syndrome (LMNS) compared with 89 healthy controls.The upper motor neuron involvement of the patients was assessed by upper motor neuron(UMN)signs and the reflex scale,and the disease severity was evaluated by the AIJS function rating scale(ALS-FRS)and APPEL ALS rate scale(AARS).Results Compared with the healthy controls(1.62±0.18),the NAA/Cr of patients with ALS(1.40±0.25)remarkably decreased (t= -5.007,P=0.000),however,it did not change in patients with LMNS(1.60±0.17)as compared with that of the controls.The NAA/Cr of patients with ALS was also lower than that of patients with LMNS(t= -2.660,P=0.009).Furthermore,the NAA/Cr of patients with definite ALS was lower than those of patients with probable and possible ALS(definite vs probable:t=-2.626,P=0.010;definite vs possible: t=-2.537,P=0.013).On the other hand,patients with pronounced UMN signs had a lower NAA/Cr ratio than those with probable UMN signs(t=-2.827,P=0.006).In patients with asymmetric clinical presentation,the NAA/Cr ratio was significantly lower in the precentral gyrus contralateral to the clinically predominantly affected side(t=-2.652,P=0.011).The NAA/Cr was correlated with the reflex scale scores,ALS-FRS score,and AARS and its sub-items(P＜0.05). Conclusions 1H-MRS is useful in studying ALS.The marker NAA/Cr of precentral gyrus may reflect the UMN degeneration in ALS,which is related to the disease severity and progression.However,it might not be helpful in the early diagnosis and differential diagnosis of the disease.
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Objective: To intensively investigate sporadic CMT patients, we have analyzed the LMNA gene in this study in a series of 32 unrelated CMT patients. Methods: Twelve exons of the LMNA gene were amplified from genetomic DNA. PCR products of each exon were analyzed by single strand conformational polymorphism (SSCP). Results: No abnormal SSCP pattern, suggesting no mutation in our CMT patients, was detected. Conclusion: The CMT diseases resulted from the mutations of LMNA gene were rare.