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.

Protective effect of Rhodiola extract against cisplatin-induced damage to TM4 sertoli cells in mice / 中华男科学杂志

<p><b>OBJECTIVE</b>To investigate the preventive effect of Rhodiola extract on cisplatin (cDDP)-induced testicular toxicity in mouse TM4 Sertoli cell line and its possible mechanism in vitro.</p><p><b>METHODS</b>We treated mouse TM4 Sertoli cells with Rhodiola extract and/or cDDP. Then we detected the proliferation of the TM4 cells by MTT assay, observed their morphological changes, and determined the contents of malondialdehyde (MDA), superoxide dismutase (T-SOD) and glutathione (GSH) in the cells.</p><p><b>RESULTS</b>MTT assay showed that Rhodiola extract at the concentration of 0.0125-2.5 mg/L significantly inhibited the cDDP-induced decrease in the proliferation of the TM4 cells (P < 0.01) and improved their morphological changes. Anti-oxidation test exhibited a dramatically increased level of MDA in the TM4 cells treated with cDDP at 0.0147 g/L as compared with the normal control cells ([3.63 +/- 0.02] vs [2.15 +/- 0.02] nmol/mg prot, P < 0.01) and decreased levels of T-SOD ([6.57 +/- 0.05] vs [10.86 +/- 0.02] U/mg prot, P < 0.01) and GSH ([1.42 +/- 0.06] vs [2.59 +/- 0.05] mg/g prot, P < 0.01). Rhodiola extract at 0.1 mg/L significantly reduced the MDA content ([1.94 +/- 0.00] nmol/mg prot, P < 0.01) and the activity of T-SOD ([8.50 +/- 0.02] U/mg prot, P < 0.01) and GSH ([2.41 +/- 0.04] mg/g prot, P < 0.01) in the TM4 cells treated with cDDP.</p><p><b>CONCLUSION</b>Rhodiola extract can significantly inhibit cDDP-induced damage to TM4 cells in mice, which may be associated with its antioxidant activity.</p>

Effects of exhaustive exercise on contractile responses mediated by beta-adrenoceptor in rat cardiac myocytes / 中国应用生理学杂志

<p><b>OBJECTIVE</b>To investigate the effects of exhaustive exercise on contraction mediated by beta-adrenoceptor (beta-AR) in rat cardiac myocytes and to analyze the mechanism by which cardiac systolic dysfunction is caused after exhaustive exercise.</p><p><b>METHODS</b>Sixteen SD rats were divided randomly into sedentary group and trained group. Cardiac myocytes were isolated from sedentary group and trained group after five times of exhaustive exercise in one week. Shortening response to norepinephrine (NE), time-to-peak contraction (TTP) and time-to-95% relaxation (R95) were measured after alpha1-AR were blocked. Also shortening responses to different levels of NE were observed.</p><p><b>RESULTS</b>Shortening amplitudes in trained rat cardiomyocytes were lower than that in sedentary group. Compared with sedentary group, shortening amplitudes induced by beta-AR stimulation were significantly decreased, meanwhile TTPs and R95 were prolonged when beta-AR were activated in trained rat cardiomyocytes. beta-AR responsiveness to NE was weakened in trained group compared with that in sedentary group.</p><p><b>CONCLUSION</b>Decreased shortening cardiomyocyte systolic function stimulating by beta-AR could result in cardiac systolic dysfunction after exhaustive exercise.</p>

siRNA silences mdr1 gene expression and reverses apoptosis resistance of K562/ADM cells line / 中华血液学杂志

<p><b>OBJECTIVE</b>To explore the effect of small interfering RNA(siRNA) on silence of mdr1 gene and reversal of apoptosis resistance in multidrug-resistant (MDR) human leukemia K562/ADM cell.</p><p><b>METHODS</b>Human MDR leukemia cell line K562/ADM was used as the target cells. Two siRNAs (mdr1 siRNA-1 and mdr1 siRNA-2) targeted mdr1 gene were chemically synthesized and transfected into K562/ADM cells with liposome. Expression of mdr1 mRNA was determined by real-time PCR, P-glycoprotein (P-gp) expression and caspase-3 activity were measured with flow cytometry (FCM), and the cell apoptosis was observed by optical and electronic microscopy for morphology and Annexin V/PI staining.</p><p><b>RESULTS</b>The mdr1 siRNA-1 and mdr1 siRNA-2 could markedly down-regulate the expression of mdr1 gene in K562/ADM cells, the expression of mdr1 mRNA decreased by 91.2% and 82.0% , and the P-gp by 74.1% and 84.4%, respectively. The caspase-3 activity was markedly enhanced, and the active caspase-3 in K562/ADM cells increased by about 40% compared to liposome alone and non-silencing controls. the sensitivity of K562/ADM cells to adriamycin-induced apoptosis was significantly augmented, the apoptotic rate of the cells treated with siRNA plus adriamycin increased by about 60% compared to adriamycin alone.</p><p><b>CONCLUSION</b>siRNAs silence the expression of mdr1/P-gp to overcome the P-gp-mediated apoptosis resistance in drug-resistant K562/ADM cells.</p>

Correlation between Qualities of Life and Depression,Anxiety for Cancer Patients / 中国康复理论与实践

@#ObjectiveTo determine the correlation between qualities of life(QOL) and depression,anxiety in cancer patients.Methods91 cancer patients was measured with self anxiety scale(SAS),self depression scale(SDS) and SF-36.ResultsDepression occurred in about 51.5% and anxiety occurred in about 24.1% of the general patients.The patients without depression showed a higher QOL than those with depression(P<0.05),and the patients without anxiety showed a higher QOL than those with anxiety(P<0.01).ConclusionDepression and anxiety are associated with poor quality of life,which should be put into plans of nursing.

Effect of embedding thread at Shenshu (BL 23) on clinical pain of postmenopausal osteoporosis / 中国针灸

<p><b>OBJECTIVE</b>To explore the effect of embedding thread at Shenshu (BL 23) on clinical pain of postmenopausal osteoporosis.</p><p><b>METHODS</b>Fifty-six cases were randomly divided into an embedding thread group, an embedding thread plus Leli group and a Leli group. The pain of the patient before treatment, 3 months and 6 months after treatment were assessed.</p><p><b>RESULTS</b>There was significant difference before and after treatment in the score of pain in both the embedding thread group and the embedding thread plus Leli group (P < 0.001), with no significant difference between the two groups (P > 0.05); there was no significant difference before and after treatment in the score of pain in the Leli group (P > 0.05), but with significant differences as compared with other two groups (both P < 0.001).</p><p><b>CONCLUSION</b>Embedding thread at Shenshu (BL 23) has very obvious therapeutic effect on clinical pain of postmenopausal osteoporosis, and oral administration of Leli capsule has no significantly therapeutic effect on clinical pain of postmenopausal osteoporosis.</p>

A peroxisome proliferator response elements regulatory system in xenopus oocytes and its application / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Peroxisome proliferator-activated receptor-gamma (PPARgamma) is a kind of ligand-activated transcription factors binding to peroxisome proliferator response element (PPRE), a specific recognition site. It is thought to play a critical role in glucose and lipid metabolism and in inflammation control. The aim of this study was to establish a new cellular model for the quick screening of lipid-lowering drugs, which may be effective as PPAR-gamma ligands on the PPRE-mediated pathway regulatory system.</p><p><b>METHODS</b>Two plasmids were constructed: pXOE-PPARgamma, in which the human PPARgamma gene was in the downstream of TFIIIA gene promoter, and pLXRN-PPRE-d2EGFP, in which the enhanced green fluorescent protein (EGFP) gene was subcloned into PPRE. The xenopus oocytes were injected with these two plasmids, and consequently treated with prostaglandin E1, pioglitazone, and different kinds of lipid-lowering drugs. After 3 days, the oocytes were observed under a fluorescence microscope. To confirm the drug action,we injected pXOE-PPARgamma plasmid into the oocytes, which then treated with prostaglandin E1 and Hawthorn flavonoids. The mass of expressed lipoprotein lipase (LPL) in the cells was determined by enzyme labeling linked immunosorbent assay (ELISA).</p><p><b>RESULTS</b>The expression of EGFP was only induced by prostagalandin E1, pioglitazone, Hawthorn flavonoids. A concentration-response relationship was seen between expressed EGFP and Hawthorn flavonoids. The levels of LPL in both Hawthorn flavonoids groups and PPARgamma ligand prostagalandin E1 group injected with pXOE-PPARgamma plasmid increased significantly (< 0.001) compared with controls, and a concentration-response relationship was observed between LPL mass and Hawthorn flavonoids.</p><p><b>CONCLUSIONS</b>It is possible to establish a PPRE regulatory EGFP reporter system in xenopus oocytes to monitor the activity of PPARgamma ligand. Hawthorn flavonoids can increase the expression of gene downsteam of PPRE by effect on the PPRE pathway regulatory system.</p>

Effect of curcumin on the gene expression of low density lipoprotein receptors / 中国结合医学杂志

<p><b>OBJECTIVE</b>To investigate the molecular mechanisms and effective target points of lipid-lowering drug, Rhizoma Curcumae Longae, and study the effect of curcumin on the expression of low density lipoprotein (LDL) receptors in macrophages in mice.</p><p><b>METHODS</b>Macrophages in mice were treated with curcumin, which was purified from the ethanolly extraction of Rhizoma Curcumae Longae for 24 h. The LDL receptors expressed in the macrophages were determined by enzyme-linked immunosorbent assay (ELISA) and assay of DiI labeled LDL uptake by flow cytometer.</p><p><b>RESULTS</b>It was found for the first time that 10 micromol/L-50 micromol/L curcumin could obviously up-regulate the expression of LDL receptor in macrophages in mice, and a dose-effect relationship was demonstrated.</p><p><b>CONCLUSION</b>One of the lipid-lowering mechanisms of traditional Chinese medicine, Rhizoma Curcumae Longae, was completed by the effect of curcumin through the up-regulation of the expression of LDL receptor.</p>

The protection of seed oil of Hippophae rharmnoides on ischemic cerebral infarction in rats / 中国中药杂志

<p><b>OBJECTIVE</b>To study the protection of seed oil of Hippophae rhamnoides on ischemic cerebral infarction in rats and the mechanism of the action.</p><p><b>METHOD</b>Focal cerebral ischemia model was made by middle cerebral artery occlusion(MCAO) in rats. Behavior obstacles of rats were observed. Cerebral infarction volume was determined by Megnetic Resonance Imaging(MRI).</p><p><b>RESULT</b>Seed oil of Hippophae rhamnides 0.7 and 0.35 g.kg-1 could markedly reduce infarction volume after occlusion of middle cerebral artery in rats and also could ameliorate the behavior obstacles of rats.</p><p><b>CONCLUSION</b>These results suggested that seed oil of Hippophae rhamnoides had distinct protection to ischemic cerebral infarction in rats.</p>