Genetic Prion Disease: Insight from the Features and Experience of China National Surveillance for Creutzfeldt-Jakob Disease / 神经科学通报·英文版

Human genetic prion diseases (gPrDs) are directly associated with mutations and insertions in the PRNP (Prion Protein) gene. We collected and analyzed the data of 218 Chinese gPrD patients identified between Jan 2006 and June 2020. Nineteen different subtypes were identified and gPrDs accounted for 10.9% of all diagnosed PrDs within the same period. Some subtypes of gPrDs showed a degree of geographic association. The age at onset of Chinese gPrDs peaked in the 50–59 year group. Gerstmann–Sträussler–Scheinker syndrome (GSS) and fatal familial insomnia (FFI) cases usually displayed clinical symptoms earlier than genetic Creutzfeldt–Jakob disease (gCJD) patients with point mutations. A family history was more frequently recalled in P105L GSS and D178N FFI patients than T188K and E200K patients. None of the E196A gCJD patients reported a family history. The gCJD cases with point mutations always developed clinical manifestations typical of sporadic CJD (sCJD). EEG examination was not sensitive for gPrDs. sCJD-associated abnormalities on MRI were found in high proportions of GSS and gCJD patients. CSF 14-3-3 positivity was frequently detected in gCJD patients. Increased CSF tau was found in more than half of FFI and T188K gCJD cases, and an even higher proportion of E196A and E200K gCJD patients. 63.6% of P105L GSS cases showed a positive reaction in cerebrospinal fluid RT-QuIC. GSS and FFI cases had longer durations than most subtypes of gCJD. This is one of the largest studies of gPrDs in East Asians, and the illness profile of Chinese gPrDs is clearly distinct. Extremely high proportions of T188K and E196A occur among Chinese gPrDs; these mutations are rarely reported in Caucasians and Japanese.

Genetic Prion Disease: Insight from the Features and Experience of China National Surveillance for Creutzfeldt-Jakob Disease / 神经科学通报·英文版

Human genetic prion diseases (gPrDs) are directly associated with mutations and insertions in the PRNP (Prion Protein) gene. We collected and analyzed the data of 218 Chinese gPrD patients identified between Jan 2006 and June 2020. Nineteen different subtypes were identified and gPrDs accounted for 10.9% of all diagnosed PrDs within the same period. Some subtypes of gPrDs showed a degree of geographic association. The age at onset of Chinese gPrDs peaked in the 50-59 year group. Gerstmann-Sträussler-Scheinker syndrome (GSS) and fatal familial insomnia (FFI) cases usually displayed clinical symptoms earlier than genetic Creutzfeldt-Jakob disease (gCJD) patients with point mutations. A family history was more frequently recalled in P105L GSS and D178N FFI patients than T188K and E200K patients. None of the E196A gCJD patients reported a family history. The gCJD cases with point mutations always developed clinical manifestations typical of sporadic CJD (sCJD). EEG examination was not sensitive for gPrDs. sCJD-associated abnormalities on MRI were found in high proportions of GSS and gCJD patients. CSF 14-3-3 positivity was frequently detected in gCJD patients. Increased CSF tau was found in more than half of FFI and T188K gCJD cases, and an even higher proportion of E196A and E200K gCJD patients. 63.6% of P105L GSS cases showed a positive reaction in cerebrospinal fluid RT-QuIC. GSS and FFI cases had longer durations than most subtypes of gCJD. This is one of the largest studies of gPrDs in East Asians, and the illness profile of Chinese gPrDs is clearly distinct. Extremely high proportions of T188K and E196A occur among Chinese gPrDs; these mutations are rarely reported in Caucasians and Japanese.

Preparation of PrP-specific Polyclonal Antibody Immunization of -knockout Mice with Recombinant Human PrP Protein / 生物医学与环境科学（英文）

Objective@#The definite diagnosis of human and animal prion diseases depends on the examination of special pathological changes and/or detection of PrP in the brain tissues of suspected cases. Thus, developing methods to obtain PrP antibody with good specificity and sensitivity is fundamental for prion identification.@*Methods@#We prepared a PrP-specific polyclonal antibody (pAb P54) in a -knockout mouse model immunization with recombinant full-length human PrP protein residues 23-231. Thereafter, we verified that pAb in Western blot, immunohistochemistry (IHC), and immunofluorescent (IFA) assays.@*Results@#Western blot illustrated that the newly prepared pAb P54 could react with recombinant PrP protein, normal brain PrP from healthy rodents and humans, and pathological PrP in the brains of experimental rodents infected with scrapie and humans infected with different types of prion diseases. The electrophoretic patterns of brain PrP and PrP observed after their reaction with pAb P54 were nearly identical to those produced by commercial PrP monoclonal antibodies. Three glycosylated PrP molecules in the brain homogenates were clearly demonstrated in the reactions of these molecules with pAb P54. IHC assay revealed apparent PrP deposits in the GdnCl-treated brain slices of 139A-infected mice and 263K-infected hamsters. IFA tests with pAb P54 also showed clear green signals surrounding blue-stained cell nuclei.@*Conclusion@#The newly prepared pAb P54 demonstrated reliable specificity and sensitivity and, thus, may have potential applications not only in studies of prion biology but also in the diagnosis of human and experimental rodent prion diseases.

Three-dimensional printed navigation template assisted core decompression and bone grafting for treatment of ARCO stage II non-traumatic femoral head necrosis / 中国组织工程研究

BACKGROUND: Core decompression and bone grafting is the main postoperative method in the treatment of ARCO stage II non-invasive necrosis of the femoral head, but there are risks of inaccurate location, incomplete or excessive removal of necrotic bone. OBJECTIVE: To observe the accuracy and safety of three-dimensional(3 D) printed navigation template assisted core decompression and bone grafting in the treatment of ARCO stage II non-traumatic femoral head necrosis. METHODS: Eighty patients(96 hips) of ARCO stage II non-traumatic femoral head necrosis were enrolled from January to November 2017 in Honghui Hospital Affiliated to Xi’an Jiaotong University. The patients were randomly divided into two groups. In the 3 D group, 40 cases(48 hips) received 3 D printed navigation template assisted core decompression and bone grafting. In the control group, 40 cases(48 hips) received core decompression and bone grafting(no navigation template). All patients signed the informed consent. This study was approved by the Hospital Ethics Committee. The operation time, intraoperative fluoroscopy, and intraoperative blood loss were recorded, and X-ray examination results at 3, 6, 12, and 24 months after operation were observed. The femoral head survival rate, hip Harris score, and pain visual analogue scale score were evaluated. The efficacy was compared. RESULTS AND CONCLUSION:(1) Compared with the control group, the operation time was shortened from(132.57±14.86) minutes to(82.63±10.31) minutes; the number of intraoperative fluoroscopy was reduced from(16.80±2.15) times to(4.93±1.36) times; blood loss was reduced from(143.23±17.98) mL to(75.64± 16.23) mL in the 3 D group. Operation time, number of fluoroscopy, and blood loss were superior in the 3 D group than in the control group(P < 0.05).(2) The 24-month follow-up of imaging showed that only 2 cases of the femoral head collapsed in the 3 D group, but the hip joint function was acceptable. There was no artificial hip arthroplasty and the femoral head survival rate was 96%. In the control group, femoral head collapsed in 9 cases. Four of them had total hip arthroplasty due to limited hip joint activity, and the femoral head survival rate was 81%. The survival rate of the femoral head in the 3 D group was higher than that in the control group(P=0.024).(3) Compared with the control group, Harris score and visual analogue scale score were improved in the 3 D group(P < 0.05).(4) Applying 3 D printed navigation template to core decompression and bone grafting for ARCO stage II non-traumatic femoral head necrosis can reduce the operation time, intraoperative fluoroscopy and blood loss, and improve the accuracy and safety of intraoperative positioning.

Platelet-rich plasma combined with core decompression and bone grafting in the treatment of non traumatic necrosis of femoral head in ARCO stageⅡ / 中国骨伤

OBJECTIVE@#To observe the clinical effect of platelet rich plasma (PRP) combined with β tricalcium phosphate bioceramic bone in the treatment of non traumatic necrosis of the femoral head in ARCO stageⅡ.@*METHODS@#From January 2017 to December 2018, 100 patients (160 hips) with ARCO stageⅡnon traumatic necrosis of the femoral head were divided into PRP group and control group. In PRP group, 50 patients (80 hips), 22 males and 28 females, aged from 18 to 65 (43.47± 7.23) years, with a course of 4 to 18 (15.8±2.9) months, underwent core decompression and bone grafting combined with PRP implantation. There were 50 cases (80 hips) in the control group, including 27 males and 23 females, aged 20 to 63 (45.72± 7.43) years, and the course of disease was 6 to 19 (14.9±3.8) months. Hip X-ay film was followed up after operation. Harris score and VAS score were used to evaluate the curative effect, and the survival rate of hip joint was recorded.@*RESULTS@#All patients had good wound healing, no infection, thrombosis and other complications. All patients were followed up for 12 to 14 (12.0±0.4) months. Twelve months after operation, the image expression of PRP group was better than that of control group(@*CONCLUSION@#Platelet-rich plasma(PRP) combined with artificialbone for core decompression and bone grafting can change the situation of simple artificial bone implantation and uncertain curative effect, improve the success rate of this operation, effectively reduce the collapse rate of femoral head necrosis in the early and middle stage, delay or even avoid hip replacement.

A new alkaloid from Corydalis Rhizoma / 中草药

Objective: To study the chemical constituents from the rhizome of Corydalis yanhusuo. Methods: The alkaloids were isolated and purified by silica column and other modern separation methods. The compounds were identified by nuclear magnetic resonance analysis. Results: Three compounds were isolated and identified as 1-[2-(N-methylaminoethy)]-3,4,6,7-tetramethoxy-phenanthrene (1), 1-(N-ethylaminomethy)-3,4,6,7-tetramethoxyphenanthrene (2), and oxoglaucidaline (3), respectively. Conclusion: Compound 1 is a new natural product, compound 2 is a new compound named coryphenanthrine A, and compound 3 is isolated from this plant for the first time.

Discussion of HPLC fingerprint of traditional Chinese medicine of Corydalis yanhusuo and its preparation / 中国中药杂志

Fingerprint of traditional Chinese medicine (TCM) is in the guidance of the basic theory of TCM, according to the variety and quality of TCM and using a variety of analytical methods and technology, to establish the objective, overall and multi index comprehensive evaluation system. The TCM fingerprint in one of the strategic subjects for TCM modernization. As more and more technologies have been applied to the fingerprint research of TCM, it is sure to play a much more important role in many aspects, such as the quality control of TCM, the researches of efficient components, and the mechanism in TCM, and so on. The fingerprint technology includes many modern technologies such as high-pressure liquid chromatography (HPLC). Corydalis yanhusuo is an ancient TCM, and recent years appears many researches about fingerprint of C. yanhusuo. This paper generalizes the research in progresses in research and analytical methods on fingerprint technology of C. yanhusuo, processed products (vinegar), and painkillers, to provide the scientific basis for fingerprint method and quality control of C. yanhusuo.

Effect of Heroin on DLG4 Expression in Hippocampus, Amygdala and Frontal Cortex of Rats / 法医学杂志

OBJECTIVE@#To observe the expression of discs large homolog 4 (DLG4) protein in hippocampus, amygdala and frontal cortex of rats and evaluate postsynaptic density in heroin dependence.@*METHODS@#The rat heroin dependent model was established by increasing intraperitoneal injection of heroin. DLG4 proteins in hippocampus, amygdala and frontal cortex of heroin dependent 9, 18, 36 days rats were detected with immunohistochemical staining and compared with that in the control group.@*RESULTS@#DLG4 proteins in hippocampus, amygdala and frontal cortex were gradually reduced with extension of heroin dependent time.@*CONCLUSION@#Heroin dependence can affect postsynaptic density of hippocampus, amygdala and frontal cortex. The changes become more apparent with extension of heroin dependence time.

Characterization of the biological activities of lyophilized recombinant adenovirus expressing the triple mutant of hypoxia inducible factor-1α / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the influence of lyophilization on the biological activity of recombinant adenovirus-mediated triple mutant of hypoxia inducible factor-1α (Ad-HIF-1α-564/402/803).</p><p><b>METHODS</b>Ad-HIF-1α-564/402/803 was amplified from HEK293A cells and purified by ultracentrifugation in CsCl gradient solutions. The infection efficiency was observed by X-gal staining. The lyophilized adenovirus was prepared under appropriate conditions. Before and after lyophilization, the effect of Ad-HIF-1α-564/402/803 on hMVEC proliferation was evaluated by MTS assay. The recombinant adenovirus was confirmed by PCR and DNA sequence analysis before and 1 day, 6 months and 12 months after lyophilization, and hMVECs infected with Ad-HIF-1α-564/402/803 at these time points were examined for HIF-1α protein expression using Western blotting.</p><p><b>RESULTS</b>No significant changes were observed in the effect of lyophilized Ad-HIF-1α-564/402/803 on hMVECs proliferation at the optimal multiplicity of infection of 100 pfu/cell (P>0.05). At the 4 time points, the recombinant adenovirus HIF-1α showed no structural alterations or significant changes in the expression level of HIF-1α protein in the transfected hMVECs (P>0.05).</p><p><b>CONCLUSION</b>Lyophilized Ad-HIF-1α-564/402/803 can maintain its biological activities for a long time.</p>

Effect of different doses of recombinant adenovirus mediated hypoxia-inducible factor-1alpha on angiogenesis in ischemic lower hind limb of rabbits / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the effect of recombinant adenovirus-mediated hypoxia-inducible factor-1alpha (Ad-HIF-1alpha) at different doses on angiogenesis in a rabbit model of hind limb ischemia.</p><p><b>METHODS</b>Left hind limb ischemia was induced in 45 Zealand white rabbits by ligation of the left femoral artery. The rabbits were randomly divided into 5 groups (n=9) to receive intramuscular injections of 0.5 ml saline, 2x10(10) PFU empty vector (Ad-null), or different doses of Ad-HIF-1alpha (2x10(9), 2x10(10) or 2x10(11) PFU) immediately after the operation. On the 7th day after the operation, real-time PCR was used to detect the expression of HIF-1alpha mRNA in the skeletal muscles. Immediately and on the 14th and 28th days after the operation, contrast enhanced ultrasound (CEU) was used to observe the blood perfusion of the hind limb. On the 28th day postoperatively, immunohistochemistry for CD31 was performed to evaluate the microvascular density (MVD).</p><p><b>RESULTS</b>Real-time PCR showed that Ad-HIF-1alpha significantly increased the expression of HIF-1alpha mRNA (P<0.01) in a dose-dependent manner as compared with that in the saline and Ad-null groups (P<0.01). CEU revealed greater blood perfusion in the hind limb of rabbits in association with increased dose of Ad-HIF-1alpha (P<0.05 or P<0.01); similar changes in the MVD was observed following Ad-HIF-1alpha injections as shown by immunohistochemistry (P<0.05 or P<0.01). No significant differences were found either in the blood perfusion or MVD between saline and Ad-null groups (P>0.05).</p><p><b>CONCLUSION</b>Ad-HIF-1alpha can dose-dependently promote the angiogenesis in the ischemic limb of rabbits.</p>

Relationship between myocardial systolic, diastolic functions and perfusion in coronary artery stenosis / 南方医科大学学报

<p><b>OBJECTIVE</b>To evaluate the relationship between myocardial systolic, diastolic functions and perfusion in coronary artery stenosis using velocity vector imaging (VVI) and myocardial contrast echocardiography (MCE).</p><p><b>METHODS</b>Stenoses in the anterior descending branch of the coronary artery were induced in 8 dogs. Before and after coronary artery stenosis, two-dimensional images of the left ventricular mastoid muscle section on the short axis at rest and in the peak dose of dobutamine were obtained for evaluation of VVI and MCE. The myocardial blood flow A.beta values, peak systolic strain rate (SRsys) and peak diastolic strain rate (SRdia) in the direction of the circumference of the short axis were measured.</p><p><b>RESULTS</b>At rest, only severe coronary stenosis resulted in significantly lowered SRsys, SRdia and A.beta value of the stenotic bed compared to the values before the stenosis (-1.1-/+0.50 vs -1.62-/+0.50, 1.19-/+0.48 vs 1.75-/+0.51, 0.4-/+0.21 vs 0.80-/+0.47, P<0.05). In stress, SRsys, SRdia and A.beta value of the stenotic bed gradually decreased as coronary stenosis worsened (-4.31-/+1.14 vs -3.20-/+0.98 vs -1.18-/+0.64, 4.51-/+1.13 vs 3.39-/+0.98 vs 1.37-/+0.64. 3.54-/+1.95 vs 1.81-/+0.89 vs 0.82-/+0.42, P<0.05). Both at rest and in stress, good correlations were noted between SRsys and SRdia (r(rest)=0.88, r(stress)=0.96, P<0.01), between SRsys and the standard A.beta values (r(rest)0.56, r(stress)=0.71, P<0.01), and between SRdia and A.beta (r(rest)=0.57, r(stress)=0.72, P<0.01) in the direction of the circumference of the short axis.</p><p><b>CONCLUSIONS</b>Using VVI and MCE, the changes in myocardial perfusion and the systolic and diastolic functions in the direction of the circumference can be observed dynamically. VVI may help assess the condition of myocardial perfusion by evaluating the systolic and diastolic function.</p>

Potassium channels and proliferation and migration of breast cancer cells / 生理学报

Potassium channels (K(+) channels), a family of special ion channel proteins, are involved in various physiological functions. Recent data show that the abnormalities of K(+) channels are not only responsible for some neurological and cardiovascular diseases but also for channelopathies. Furthermore, many groups reported that the abnormalities of K(+) channels had shown their oncogenic potential in breast introduction and other malignant tumors, promoting proliferation, invasion and metastasis. The aim of this review is to give an updated introduction of research progress in K(+) channels associated with breast cancer.

Effect of phospholipid- and albumin-coated microbubbles for myocardial opacification: a comparative study / 南方医科大学学报

<p><b>OBJECTIVE</b>To evaluate the effect of a phospholipid-coated microbubble contrast agent for myocardium opacification in comparison with a albumin-coated microbubble contrast agent (Quanfuxian).</p><p><b>METHODS</b>In 10 dogs with single coronary artery stenosis involving the anterior descending branch or circumflex branch randomly received infusion of the two contrast agents through the femoral vein. The myocardial blood flow, heart rate and blood pressure were analyzed qualitatively and quantitatively. The concentration and the particle diameter of the two contrast agents were determined.</p><p><b>RESULTS</b>The concentration of the phospholipid-coated microbubbles was (1.06-/+0.22) x10(9)/ml, with a diameter of 3.04-/+0.34 microm, similar to the concentration and diameter of Quanfuxian ((1.31-/+0.33)x10(9)/ml and 2.88-/+0.58 microm, respectively, P>0.05). Both of the agents achieved grade three myocardium opacification, and produced no obvious effect on the heart rate and blood pressure. Quantitative analysis of myocardial opacification in terms of myocardial blood volume (A), blood velocity (beta), and blood flow (A x beta) revealed no significant difference between the two agents (P>0.05), and the parameters derived from the two agents showed good correlations (P<0.05, rA=0.809, r beta=0.932, rA.beta=0.925).</p><p><b>CONCLUSION</b>The phospholipid-coated microbubble contrast agent shows good effect for myocardial opacification without significant difference from Quanfuxian. Both of the agents are good ultrasound contrast agents for quantitative analysis of myocardium blood flow.</p>

Clinical Characteristics of 100 Children with Cerebral Palsy / 中国康复理论与实践

@#ObjectiveTo analysis the clinical characteristics and the high risk factors of children with cerebral palsy.MethodsClinical data of 100 children with cerebral palsy were retrospectively analyzed.Results51% of children were born with asphyxia, 42% were born prematurely, 39% were low birth body weight. 85.7% of children involved had mental retardation, 12% had hearing loss and 7% had visual impairment. 88% of children involved had abnormal cranial CT results and 46.1% had abnormal EEG. 50.0% of the children had abnormal brain stem auditory evoked potentials.ConclusionAsphyxia, prematurely birth and low birth body weight are high risk factors of cerebral palsy. Most of the children with cerebral palsy in this group are mental retarded.