Anti-HMGCR immune-mediated necrotizing myopathy: A case report / 北京大学学报(医学版)

The patient was a 55-year-old man who was admitted to hospital with "progressive myalgia and weakness for 4 months, and exacerbated for 1 month". Four months ago, he presented with persistent shoulder girdle myalgia and elevated creatine kinase (CK) at routine physical examination, which fluctuated from 1 271 to 2 963 U/L after discontinuation of statin treatment. Progressive myalgia and weakness worsened seriously to breath-holding and profuse sweating 1 month ago. The patient was post-operative for renal cancer, had previous diabetes mellitus and coronary artery disease medical history, had a stent implanted by percutaneous coronary intervention and was on long-term medication with aspirin, atorvastatin and metoprolol. Neurological examination showed pressure pain in the scapularis and pelvic girdle muscles, and V- grade muscle strength in the proximal extremities. Strongly positive of anti-HMGCR antibody was detected. Muscle magnetic resonance imaging (MRI) T2-weighted image and short time inversion recovery sequences (STIR) showed high signals in the right vastus lateralis and semimembranosus muscles. There was a small amount of myofibrillar degeneration and necrosis, CD4 positive inflammatory cells around the vessels and among myofibrils, MHC-Ⅰ infiltration, and multifocal lamellar deposition of C5b9 in non-necrotic myofibrils of the right quadriceps muscle pathological manifestation. According to the clinical manifestation, imageological change, increased CK, blood specific anti-HMGCR antibody and biopsy pathological immune-mediated evidence, the diagnosis of anti-HMGCR immune-mediated necrotizing myopathy was unequivocal. Methylprednisolone was administrated as 48 mg daily orally, and was reduced to medication discontinuation gradually. The patient's complaint of myalgia and breathlessness completely disappeared after 2 weeks, the weakness relief with no residual clinical symptoms 2 months later. Follow-up to date, there was no myalgia or weakness with slightly increasing CK rechecked. The case was a classical anti-HMGCR-IMNM without swallowing difficulties, joint symptoms, rash, lung symptoms, gastrointestinal symptoms, heart failure and Raynaud's phenomenon. The other clinical characters of the disease included CK as mean levels >10 times of upper limit of normal, active myogenic damage in electromyography, predominant edema and steatosis of gluteus and external rotator groups in T2WI and/or STIR at advanced disease phase except axial muscles. The symptoms may occasionally improve with discontinuation of statins, but glucocorticoids are usually required, and other treatments include a variety of immunosuppressive therapies such as methotrexate, rituximab and intravenous gammaglobulin.

Induced pluripotent stem cell-derived motor neurons from amyotrophic lateral sclerosis (ALS) patients carrying different superoxide dismutase 1 mutations recapitulate pathological features of ALS / 中华医学杂志(英文版)

BACKGROUND@#Investigations of the pathogenic mechanisms in motor neurons (MNs) derived from amyotrophic lateral sclerosis (ALS) disease-specific induced pluripotent stem (iPS) cell lines could improve understanding of the issues affecting MNs. Therefore, in this study we explored mutant superoxide dismutase 1 (SOD1) protein expression in MNs derived from the iPS cell lines of ALS patients carrying different SOD1 mutations.@*METHODS@#We generated induced pluripotent stem cell (iPSC) lines from two familial ALS (FALS) patients with SOD1-V14M and SOD1-C111Y mutations, and then differentiated them into MNs. We investigated levels of the SOD1 protein in iPSCs and MNs, the intracellular Ca2+ levels in MNs, and the lactate dehydrogenase (LDH) activity in the process of differentiation into the MNs derived from the controls and ALS patients' iPSCs.@*RESULTS@#The iPSCs from the two FALS patients were capable of differentiation into MNs carrying different SOD1 mutations and differentially expressed MN markers. We detected high SOD1 protein expression and high intracellular calcium levels in both the MN and iPSCs that were derived from the two SOD1 mutant patients. However, at no time did we observe stronger LDH activity in the patient lines compared with the control lines.@*CONCLUSIONS@#MNs derived from patient-specific iPSC lines can recapitulate key aspects of ALS pathogenesis, providing a cell-based disease model to further elucidate disease pathogenesis and explore gene repair coupled with cell-replacement therapy. Incremental mutant expressions of SOD1 in MNs may have disrupted MN function, either causing or contributing to the intracellular calcium disturbances, which could lead to the occurrence and development of the disease.

Epidemiology and factors predicting survival of amyotrophic lateral sclerosis in a large Chinese cohort / 中华医学杂志(英文版)

BACKGROUND@#Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder associated with loss of motor neurons. Our objective was to explore the epidemiology, clinical features, and survival factors of 1809 patients with ALS.@*METHODS@#We analyzed 1809 ALS patients, who were recruited from the Peking University Third Hospital from January 2005 to December 2015. Demographic data and disease-related parameters were collected. Kaplan-Meier curves were used to compare survival time. Cox proportional hazards function and the hazard ratio were used to identify adjusted prognostic predictors.@*RESULTS@#The results showed that the average annual incidence in Beijing alone was 0.38 cases/100,000 person-years and the mean age of onset was 48.88 ± 11.35 (95% confidence interval [CI]: 48.17-49.85) years. The median survival time from onset to death/tracheostomy was 58.89 ± 33.03 (95% CI: 51.46-63.84) months. In the adjusted Cox proportional hazard model, age of onset, diagnosis delay, rate of disease progression (Amyotrophic Lateral Sclerosis Functional Rating Scale Revised decline [points/month]), and body mass index all had an independent effect on survival in ALS.@*CONCLUSIONS@#Our study provides information on epidemiology, clinical features, and survival factors of patients with ALS in China. These results can be helpful in clinical practice, clinical trial design, and validation of new tools to predict disease progression.

Mechanical thrombectomy treatment in patients with acute ischemic stroke: a single center study / 北京大学学报(医学版)

OBJECTIVE@#To evaluate the effectiveness and safety of mechanical thrombectomy treatment in patients with acute ischemic stroke (AIS),and to explore influential factors of the clinical prognosis preliminarily.@*METHODS@#Clinical data of 26 patients with acute cerebral arterial occlusion treated with mechanical thrombectomy in Peking University Third Hospital from January 2014 to June 2017 were retrospectively collected. The immediate effects of the 26 patients in this group after mechanical thrombectomy treatment were analyzed,The national institutes of health stroke scale (NIHSS) scores between preoperative and at discharge of the 26 patients in this group were compared,and modified Rankin scale (mRS) scores of 90 days post operation were analyzed to assess the prognosis of the 26 patients in this group.@*RESULTS@#(1)In this group, 23 patients (88.5%) achieved vascular recanalization evaluated by thrombolysis in cerebral ischemia scale scores [thrombolysis in cerebral ischemia scale (TICI) scores, 3/2b grades were recognized as vascular recanalization], 19 patients of them reached TICI grade 3 and 4 atients reached TICI grade 2b. In this group 3 patients (11.5%) encountered symptomatic intracranial hemorrhage, 2 patients of them recovered after cerebral hemorrhage absorbed and 1 patient died of massive cerebral hemorrhage. In this group 4 patients (15.4%) died after mechanical thrombectomy treatment,2 patients died of hernia of the brain caused by severe cerebral edema, 1 patient died of symptomatic intracranial hemorrhage and 1 patient died of extensive subarachnoid hemorrhage. (2)The assessment of NIHSS scores at discharge(5.3±2.1)showed significantly lower than those preoperatively(12.6±4.2), P<0.01,and in this group 12 patients (46.2%) achieved favourable prognosis (defined as mRS scores 0-2), 6 patients of them reached mRS 0 score,4 patients reached mRS 1 score and 2 patients reached mRS 2 scores.@*CONCLUSION@#Mechanical thrombectomy with stent retriever contributed to a high rate of vascular recanalization and favourable prognosis,but some patients had poor prognosis, suggesting that we should screen the enrolled patients strictly.

Morroniside improves the neurological function in intracerebral hemorrhage rats by inhibiting inflammatory response / 中国组织工程研究

BACKGROUND: Morroniside has been shown to play roles of anti-inflammation, antioxidant, anti-apoptosis, promoting vascular and neural regeneration, anti-platelet aggregation and neuroprotection in the rat model of ischemic brain injury, but whether it can inhibit the inflammatory reaction of cerebral hemorrhage is unclear. OBJECTIVE: To observe the changes of inflammatory factors (interleukin-1, tumor necrosis factor-α) and inflammatory-related proteins (nuclear factor-κB and SUMO2/3) as well as neurologic function in a rat model of cerebral hemorrhage treated with morroniside at different doses. METHODS: Healthy male Sprague-Dawley rats were randomly divided into sham operation, cerebral hemorrhage and low-, medium- and high-dose morroniside groups. The model of cerebral hemorrhage was established in the latter four groups by injecting autologous blood from the tail artery, followed by intragastric injection of 30, 90, 270 mg/kg morroniside in the three morronicide groups, respectively, three times daily for consecutive 7 days; the rats in the sham operation and model groups were given same volume of normal saline. Then, the neurological function was evaluated by Neurological Severity Scores; the brain tissue around the hematoma were removed to observe the morphological changes of neurocytes around the hematoma by hematoxylin-eosin staining; the expression levels of interleukin-1 and tumor necrosis factor α in the brain tissue were detected by ELISA; the expression levels of nuclear factor-κB and SUMO2/3 were detected by immunohistochemistry and western blot assay. RESULTS AND CONCLUSION: Compared with the icerebral hemorrhage group, the low-, medium- and high-dose morroniside groups showed a significnat neurological improvement, especially the high-dose group (P < 0.05). Compared with the sham operation group, the cerebral hemorrhage and morroniside groups exhibited a significant increase in the nerve function damage and expression levels of interleukin-1, tumor necrosis factor α, nuclear factor-κB and SUMO2/3 (P < 0.05). Compared with the cerebral hemorrhage group, in the low-, medium- and high-dose morroniside groups, the expression levels of interleukin-1 and tumor necrosis factor α were significantly reduced, and expression levels of nuclear factor-κB and SUMO2/3 were significantly increased (P < 0.05). In summary, high-dose morroniside can improve the neurological function in rats with cerebral hemorrhage by down-regulating the levels of inflammatory cytokines.

ERKl/2 signaling pathway mediates heme oxygenase-1 up-regulation by minocycline in PC12 cells exposed to oxygen glucose deprivation / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the effects of minocycline in promoting the survival of pheochromocytoma (PCI2) cells exposed to oxygen glucose deprivation (OGD) and explore the underlying mechanisms.</p><p><b>METHODS</b>An in vitro cell model of cerebral ischemia was established by OGD for 6 h in PCI2 cells with pretreatment with minocycline or an ERK1/2 inhibitor. At 24 h after OGD injury, the cells were evaluated for cell viability by MTT assay and expressions of heme oxygenase-I (HO-I) and phospholylated extracellular signal-regulated protein kinase 1/2 (ERK1/2) by Western blotting.</p><p><b>RESULTS</b>The cell viability decreased dramatically following OGD. Pretreatment with minocycline (O.I-IO JJ.mol/L) induced a significant increase in the cell viability after OGD and caused up-regulation of HO-I protein and enhanced ERK1/2 phospholylation, and the effects were especially obvious with 1 JJ.mol/L minocycline and were abolished by inhibition of ERK1/2 activity with UOI26 (IO JJ.mol/L).</p><p><b>CONCLUSION</b>Minocycline can protect PCI2 cells against OGD-induced toxicity by up-regulating HO-I protein expression through ERKl/2 signaling pathways.</p>

Single-nucleotide Polymorphism rs2275294 in ZNF512B is not Associated with Susceptibility to Amyotrophic Lateral Sclerosis in a Large Chinese Cohort / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease that primarily affects motor neurons and has no effective treatment. Recently, Iida et al. identified a single-nucleotide polymorphism (SNP) rs2275294 in the ZNF512B gene that is significantly associated with susceptibility to ALS in the Japanese population. Here, we performed a case-control study examining the possible association of rs2275294 with risk of sporadic ALS (SALS) in a large Chinese cohort.</p><p><b>METHODS</b>To assess this association, we performed a replication study in 953 SALS patients and 1039 age- and gender-matched healthy control subjects, who were recruited from Peking University Third Hospital and the First Affiliated Hospital of Anhui Medical University from January 2004 to December 2013 throughout China. We genotyped the rs2275294 SNP using polymerase chain reaction and direct sequencing.</p><p><b>RESULTS</b>The allele frequency of rs2275294 in ZNF512B was different between Japanese and Chinese. The association in Chinese between ALS patients and controls did not reach statistical significance (P = 0.54; odds ratio = 0.94; 95% confidence interval = 0.76-1.15).</p><p><b>CONCLUSIONS</b>The SNP rs2275294 in ZNF512B is not considered to be associated with ALS susceptibility in the Chinese population. Our study highlights genetic heterogeneity in ALS susceptibility in different population. Given our negative results, further replication study involving larger and more homogeneous samples in different ethnicities should be performed in the future.</p>

Short-term curative effect of ribavirin combination therapy with pegylated interferon alfa-2a vs. interferon alfa-2a in patients with chronic hepatitis C / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To perform a retrospective cohort study in order to determine the differences in short-term curative effect of ribavirin in combination with interferon alfa (IFNa)-2a vs. pegylated (Peg)-IFNa-2a in patients with chronic hepatitis C (CHC).</p><p><b>METHODS</b>One-hundred-and-eighty-eight treatment of the CHC patients who were administered combination therapy of ribavirin with IFNa from 2010 to 2012. One-hundred-and-thirty-three of the patients received the therapy with IFNa-2a and the remaining 55 received Peg-IFNa-2a. Hepatitis C virus (HCV) load and levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were measured at treatment weeks 4, 12, 24, and 48. Adverse reactions were recorded. Differences between the groups were assessed by statistical analysis.</p><p><b>RESULTS</b>The patients in the Peg-IFNa-2a group and the IFNa-2a group showed no significant difference in sex distribution, age, smoking habits, or drinking habits at baseline (all P more than 0.05). Both antiviral therapies significantly reduced the HCV load and levels of ALT and AST (baseline levels vs. all treatment weeks examined, P less than 0.05); however, the reduction in the HCV load at week 4 was significantly more robust with the Peg-IFNa-2a therapy (2.96 ± 0.66) log10 IU/ ml vs. (3.47 ± 1.42)1og10 IU/ml; F =4.14, P=0.04). The Peg-IFNa-2a group also showed a significant higher rate of rapid virological response (RVR) than the IFNa-2a group (72.72% vs .57.14%; x²=4.37, P=0.04), but there were no statistically significant differences found between the two groups for early virological response rate (EVR), endpoint antiviral treatment virologic response rate (ETR), biochemical response rate, or rate of adverse reactions (all P more than 0.05).</p><p><b>CONCLUSION</b>Ribavirin in combination with Peg-IFNa-2a produces a better RVR than in combination with IFNa-2a .Yet, the EVR, ETR, biochemical response rate, and rate of adverse reactions is similar for the two forms of IFNa-2a. Further studies are required to determine the potential superiority of Peg-IFNa-2a for a long-term curative effect.</p>

Effect of renal sympathetic denervation on left ventricular hypertrophy and inflammatory factors in spontaneously hypertensive rats / 浙江大学学报·医学版

<p><b>OBJECTIVE</b>To investigate the effect of renal sympathetic denervation on left ventricular hypertrophy and inflammatory factors in spontaneously hypertensive rats.</p><p><b>METHODS</b>Thirty six spontaneously hypertensive rats (SHR) were divided into 3 groups with 12 animals in each group: SHR control group,operation group and sham operation group. Bilateral renal sympathectomy or sham operation were performed in operation and sham groups,respectively; another 12 WKY rats served as normal controls. The blood pressure and body weight were examined weekly. The animals were sacrificed at w1 and w6, rat hearts were collected and left ventricular mass index (LVMI) was calculated. The expression of TLR4,TNF-α and IL-6 in heart tissue were detected by immunohistochemistry and Western blot.</p><p><b>RESULTS</b>The systolic blood pressure [(201.67 ± 11.09) mmHg compared with (140.0 ± 10.86)mmHg,P<0.05],diastolic blood pressure [(144.50 ± 10.48)mmHg compared with (78.50 ± 7.32)mmHg,P<0.05], LVMI (2.44 ± 0.05 compared with 1.93 ± 0.05,P<0.05),the expression of TLR4 (0.298 ± 0.004 compared with 0.126 ± 0.004, P<0.05), NF-κB (0.249 ± 0.006 compared with 0.195 ± 0.005, P<0.05),TNF-α(0.323 ± 0.004 compared with 0.146 ± 0.004,P <0.05), IL-6 (0.283 ± 0.005 compared with 0.207 ± 0.006, P<0.05) in SHR control group were significantly higher than those in WKY group. Compared to sham operation group,the systolic blood pressure (157.30 ± 9.35 compared with 197.30 ± 11.5, P<0.05),diastolic blood pressure (112.50 ± 6.25 compared with 146.80 ± 7.6, P<0.05),LVMI (2.32 ± 0.04 compared with 2.57 ± 0.09, P<0.05, TLR4 (0.198 ± 0.006 compared with 0.317 ± 0.008, P<0.05), NF-κB (0.208 ± 0.006 compared with 0.332 ± 0.007, P<0.05), TNF-α(0.27 ± 0.009 compared with 0.375 ± 0.004,P<0.05), IL-6 (0.218 ± 0.004 compared with 0.376 ± 0.009, P<0.05) in operation group were all decreased at w1 after sympathectomy. Six weeks after the operation,there were no significant differences in systolic blood pressure (197.50 ± 12.13 compared with 208.83 ± 10.23,P>0.05) and diastolic blood pressure (150.33 ± 7.74 compared with 151.50 ± 8.22, P>0.05) between denervated and sham-operated SHRs; however,the LVMI (2.46 ± 0.07 compared with 2.81 ± 0.05,P<0.05) and the expression of TLR4(0.301 ± 0.009 compared with 0.567 ± 0.006, P<0.05), NF-κB (0.251 ± 0.004 compared with 0.476 ± 0.009,P<0.05),TNF-α(0.324 ± 0.005 compared with 0.535 ± 0.006, P<0.05,IL-6 (0.285 ± 0.009 compared with 0.549 ± 0.007, P<0.05) in operation group were still significantly lower than those in sham operation group.</p><p><b>CONCLUSION</b>Renal sympathetic denervation can significantly delay the progression of LVH in SHR, which may associated with lowering blood pressure and decreasing expression of TLR4, NF-κB,TNF-α, IL-6 in myocardial tissue.</p>

Current studies and prospect of anti-thrombotic effect of Cordyceps fungi / 中国中药杂志

Cordyceps is an entomogenous fungi developed after being infected by insects or arthropods. Many varieties of entomogenous fungus show a huge application prospect in functional food and biological medicine fields. Among them, famous herb C. sinensis is their most excellent representative, and mainly used to replenish kidneys and moisten lungs, treating fatigue, night sweating, cardiovascular diseases, respiratory diseases, hypertension, hyperlipidemia, hyperglycemia, renal failure and so on. Currently, as a medicinal resource, C. sinensis has aroused attention from the world. In the past 20 years, many studies found that Cordyceps fungi show the anti-thrombotic effect, as well as a good potential for becoming a patent medicine. This article summarizes studies on Cordyceps fungi's effects in reducing blood viscosity and resisting platelet aggregation and anticoagulant, so as to provide thought for developing and utilizing these resources as anti-thrombotic medicines.

Urethroplasty with pedunculated preputial flap and testicular tunica vaginalis for long anterior urethral stricture: A case report and review of the literature / 中华男科学杂志

<p><b>OBJECTIVE</b>To explore the treatment of urethral stricture.</p><p><b>METHODS</b>We retrospectively studied the clinical data of 1 case of long anterior urethral stricture treated by urethroplasty with pedunculated preputial flap and testicular tunica vaginalis, and summarized the treatment of the disease with review of the relevant literature.</p><p><b>RESULTS</b>The operation was smooth and successful, and no such complications as fistula and urethral stricture were found during the follow-up.</p><p><b>CONCLUSION</b>Urethroplasty with pedunculated preputial flap and testicular tunica vaginalis as a substitute is feasible for the treatment of urethral stricture. The key to a successful operation is the proper choice of a urethral substitute.</p>

Controlled clinical trials of therapeutic effects of Chinese herbs promoting blood circulation and removing blood stasis on the treatment of reflex sympathetic dystrophy with type of stagnation of vital energy and blood stasis / 中国骨伤

<p><b>OBJECTIVE</b>To observe clinical results of Chinese herbs promoting blood circulation and removing blood stasis on the treatment of reflex sympathetic dystrophy (RSD) with type of stagnation of vital energy and blood stasis.</p><p><b>METHODS</b>RSD with type of stagnation of vital energy and blood stasis was distinguished as erubescence, high temperature, perspiration, damp and acro-edema, with middle level pain. From 2006 to 2008, 58 patients with RSD of stagnation of vital energy and blood stasis were randomly divided into the treatment group (30 cases) and the control group (28 cases). The former were treated with Chinese medicine to activate blood circulation and improve bone and muscle nourishment. Chinese medicine includes: Caesalpinia Sappan 10 g, Ligusticum Chuanxiong 6 g, Frankincense 6 g, Angelica 10 g, Safflower 6 g, Myrrh 6 g, Ground Beetle 10 g, Araliaceae 3 g, Radix Paeoniae Rubra 10 g, Pericarpium Citri Reticulatae 5 g, Lawn Pennywort Herb 15 g, Manis Pentadactyla 10 g, Corydalis Yanhusuo 10 g, Rhizoma Drynariae 15 g, which were boiled into decoction and the patients were take orally everyday with a course of treatment for 10 days, together with the boiled Chinese traditional medicine of stretching muscle and activating blood circulation to fume and wash the limbs twice everyday. The compatibility of medicines in prescription includes: Lycopodium Japanicum Grass 10 g, Gentiana Macrophylla Pall 10 g, Radix Angelicae Pubescentis 10 g, Angelica 10 g, Uncaria 10 g, Frankincense 6 g, Myrrh 6 g, Safflower 6 g. Control group were treated with a placebo of the same color for oral use and external application. The delivery times, method and the time of therapy were all the same as the treatment group. After 30 days' treatment, the effective indexes of VAS pain score and swelling condition were observed in both groups.</p><p><b>RESULTS</b>VAS pain score: the treatment group decreased (3.8 +/- 0.8) points and the control group decreased (1.0 +/- 0.3) points, the difference between the two groups was significantly (P < 0.01). There was significantly difference in volume decrease of the swelling limb between treatment group (21.8 +/- 2.5) ml and the control group (10.3 +/- 2.1) ml (P < 0.01). The efficiency difference between treatment group and control group was significantly(P<0.01).</p><p><b>CONCLUSION</b>With the different treatment based on different syndrome and emphasis on the nourishment of bone and soft tissue, treated by Chinese medicine to promote blood circulation and remove blood stasis in stagnation of vital energy and blood stasis, RSD get a favorable result.</p>

Expression of cyclooxygenase-2 and vascular endothelial growth factor in human prostate cancer and its significance / 中华男科学杂志

<p><b>OBJECTIVE</b>To evaluate expressions of cyclooxygenase-2 (COX-2) and vascular endothelial growth factor (VEGF) in primary prostate cancer and its clinical significance.</p><p><b>METHODS</b>Expressions of COX-2 and VEGF were detected by immunohistochemical assay in tissues of 40 prostate cancer and 10 benign prostatic hyperplasia samples.</p><p><b>RESULTS</b>COX-2 and VEGF levels in prostate cancer were much higher than those in BPH. The degrees of cancer malignancy and invasion positively correlated with the expressions of COX-2 and VEGF. COX-2 level positively correlated with VEGF level.</p><p><b>CONCLUSION</b>The abnormal expression of COX-2 plays an important role in the development of primary prostate cancer. COX-2 and VEGF are good molecular markers of prostate cancer which are hopeful to be used for the assistant diagnosis and the prediction of prognosis of prostate cancer.</p>