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.

Effect of diosgenin on mTOR/FASN/HIF-1α/VEGFA expression in rats with non-alcoholic fatty liver disease / 中国中药杂志

The present study aimed to investigate the effect of diosgenin on mammalian target of rapamycin(mTOR), fatty acid synthase(FASN), hypoxia inducible factor-1α(HIF-1α), and vascular endothelial growth factor A(VEGFA) expression in liver tissues of rats with non-alcoholic fatty liver disease(NAFLD) and explore the mechanism of diosgenin on lipogenesis and inflammation in NAFLD. Forty male SD rats were divided into a normal group(n=8) fed on the normal diet and an experimental group(n=32) fed on the high-fat diet(HFD) for the induction of the NAFLD model. After modeling, the rats in the experimental group were randomly divided into an HFD group, a low-dose diosgenin group(150 mg·kg~(-1)·d~(-1)), a high-dose diosgenin group(300 mg·kg~(-1)·d~(-1)), and a simvastatin group(4 mg·kg~(-1)·d~(-1)), with eight rats in each group. The drugs were continuously given by gavage for eight weeks. The levels of triglyceride(TG), total cholesterol(TC), low-density lipoprotein cholesterol(LDL-C), alanine transaminase(ALT), and aspartate transaminase(AST) in the serum were detected by the biochemical method. The content of TG and TC in the liver was detected by the enzyme method. Enzyme-linked immunosorbent assay(ELISA) was used to measure interleukin 1β(IL-1β) and tumor necrosis factor α(TNF-α) in the serum. Lipid accumulation in the liver was detected by oil red O staining. Pathological changes of liver tissues were detected by hematoxylin-eosin(HE) staining. The mRNA and protein expression levels of mTOR, FASN, HIF-1α, and VEGFA in the liver of rats were detected by real-time fluorescence-based quantitative polymerase chain reaction(PCR) and Western blot, respectively. Compared with the normal group, the HFD group showed elevated body weight and levels of TG, TC, LDL-C, ALT, AST, IL-1β, and TNF-α(P<0.01), increased lipid accumulation in the liver(P<0.01), obvious liver steatosis, up-regulated mRNA expression levels of mTOR, FASN, HIF-1α, and VEGFA(P<0.01), and increased protein expression levels of p-mTOR, FASN, HIF-1α, and VEGFA(P<0.01). Compared with the HFD group, the groups with drug treatment showed lowered body weight and levels of TG, TC, LDL-C, ALT, AST, IL-1β, and TNF-α(P<0.05, P<0.01), reduced lipid accumulation in the liver(P<0.01), improved liver steatosis, decreased mRNA expression levels of mTOR, FASN, HIF-1α, and VEGFA(P<0.05, P<0.01), and declining protein expression levels of p-mTOR, FASN, HIF-1α, and VEGFA(P<0.01). The therapeutic effect of the high-dose diosgenin group was superior to that of the low-dose diosgenin group and the simvastatin group. Diosgenin may reduce liver lipid synthesis and inflammation and potentiate by down-regulating the mTOR, FASN, HIF-1α, and VEGFA expression, playing an active role in preventing and treating NAFLD.

Clinical application of serum Golgi protein 73 in patients with chronic liver diseases / 中华肝脏病杂志

Golgi protein 73 (GP73) is a transmembrane protein on the Golgi apparatus and can be cut and released into the blood. In recent years, an increasing number of clinical studies have shown that the elevated serum GP73 level is closely related to liver diseases. And thus GP73 is expected to be used as a new serum marker for assessing progress of chronic liver diseases. Herein, the clinical application of serum GP73 in chronic hepatitis, liver fibrosis, liver cirrhosis and hepatocellular carcinoma with different etiologies was reviewed based on available literatures; and a research outlook in this field is made.

Analysis of Chemical Composition in Sancao Baogan Decoction Based on UPLC-ESI-HRMSn / 中国实验方剂学杂志

Objective::To analysis the chemical constituents in Sancao Baogan decoction by ultra-high performance liquid chromatography coupled with hybrid quadrupole-orbitrap mass spectrometry (UPLC-ESI-HRMSn). Method::The separation was performed on an ACQUITY UPLC BEH C18 column (2.1 mm×100 mm, 1.7 μm) by a gradient elution of methanol (A)-0.1% formic acid solution (B) (0-2 min, 5%A; 2-20 min, 5%-12%A; 20-35 min, 12%-40%A; 35-38 min, 40%A; 38-48 min, 40%-80%A; 48-50 min, 80%A). The flow rate was 0.3 mL·min-1 and the column temperature was set at 30 ℃, the injection volume was 10 μL. Electrospray ionization was applied and the data were collected via positive and negative ion modes. By using Xcalibur 3.0 software, the chemical constituents were analyzed based on the relative retention time, excimer ion peak and fragment ion peak of the compounds, as well as comparison with human metabolome database (HMDB), reference substances and literature data. Result::A total of 40 chemical components were identified from Sancao Baogan decoction, including 16 phenolic acids, 19 flavonoids, 2 anthraquinones, 1 triterpenoid, 1 sterol, and 1 monoterpenoid. Six compounds (dansensu, α-pinene, epigallocatechin, 2, 5-dihydroxybenzoic acid, naringenin and emodin) were reported for the first time from Sancao Baogan decoction. Conclusion::The established UPLC-ESI-HRMSn can quickly, accurately and comprehensively analyze the chemical constituents of Sancao Baogan decoction, which lays a foundation for the basic research of pharmacodynamic substances and quality control of this formula.

Study on identification of different producing areas of Gastrodia elata using multivariable selection and two-dimensional correlation spectroscopy of near infrared spectroscopy / 中国中药杂志

The efficacy and quality of Gastrodia elata from different producing areas are significant difference. The identification of producing area is helpful for the scientific and reasonable usage of medicinal material. Application near infrared spectroscopy( NIR) together with variance spectra,principal component analysis( PCA),interval partial least squares( i PLS) and genetic algorithm( GA),the characteristic spectra of G. elata from inside and outside of Yunnan province( except Zhaotong) and Zhaotong were extracted,and the pattern recognition models of i PLS-DA and GA-SVM were built,and the suitability of the models were also validated. The results showed that the prediction accuracy of i PLS-DA model was 96. 15%,the values of R2,RMSECV and RMSEP were 0. 893,0. 224 and0. 321,respectively. The prediction accuracy of GA-SVM model was 100% and RMSECV was 0. 719 4. Both methods could identify G. elata from different producing area preferably. Further,two-dimensional spectroscopy analysis was conducted for the characteristic spectra extracted by i PLS and GA. The results showed that the differential spectra of G. elata from outside and inside Yunnan were mainly located in the absorption areas of the stretch,bending and double frequency of C-H,C-N,O-H and N-H bonds of polysaccharides,aromatic hydrocarbon,amides and starch. The differential spectra of G. elata from outside Yunnan and Zhaotong were mainly located in the absorption areas of the stretch,bending and double frequency of C-H,O-H and N-H bonds of vegetable protein,aromatic hydrocarbon,polysaccharides,and alcohols. The differential spectra of G. elata from inside Yunnan and Zhaotong were mainly located in the absorption areas of the stretch,bending,transformation and double frequency of CHO,N-H,C-H,O-H and HOH bonds of lignin,aromatic hydrocarbon,alcohols,polysaccharides and aliphatics. Effective recognition of different producing areas and exploration the difference of component of G. elata could be conducted through NIR combined with multivariable selection and two-dimensional spectroscopy,which provided the basis for the reasonable development and efficient utilization of G. elata.

Effect of acupuncture plus medication on the pulmonary ventilation, IFN-γ level and sleep quality in allergic rhinitis patients / 针灸推拿医学（英文版）

Objective:To observe the effect of warm-unblocking acupuncture plus fluticasone propionate nasal spray on the pulmonary ventilation, level of interferon-γ (IFN-γ) and sleep quality in patients with allergic rhinitis (AR). Methods: A total of 112 AR patients were enrolled between January 2013 and August 2018 and were divided into an observation group and a control group by the random number table method, with 56 cases in each group. Patients in the observation group received warm-unblocking acupuncture plus fluticasone propionate nasal spray, and patients in the control group only received fluticasone propionate nasal spray. The nasal symptom score, pulmonary function indexes, the levels of IFN-γ and interleukin (IL)-4 in serum, and sleep quality in the two groups were compared. Results: After treatment, the total effective rate in the observation group was higher than that in the control group (P＜0.05). The nasal symptom score dropped in both groups after treatment (both P＜0.05), and the score in the observation group was lower than that in the control group (P＜0.05). The pulmonary ventilation indexes all increased significantly after treatment in the observation group (all P＜0.05); the forced expiratory volume in 1 second (FEV1) to forced vital capacity (FVC) ratio (FEV1/FVC) and the forced expiratory flow at 50%, 75% and 25%-75% of the vital capacity (FEF50%, FEF75%, FEF25%-75%) increased after treatment in the control group (all P＜0.05); the pulmonary ventilation indexes were higher in the observation group than those in the control group (all P＜0.05). The level of IFN-γ increased significantly after treatment in the two groups (both P＜0.05) and the level of IL-4 dropped significantly (both P＜0.05); the observation group had a higher IFN-γ level (P＜0.05) and a lower IL-4 level (P＜0.05) compared with the control group. Regarding the Pittsburgh sleep quality index (PSQI), the scores of subjective sleep quality, habitual sleep efficiency and sleep disturbances and the general PSQI score decreased significantly after treatment in both groups (all P＜0.05), and the scores in the observation group were significantly lower than those in the control group (all P＜0.05). Conclusion: Warm-unblocking acupuncture plus fluticasone propionate nasal spray can effectively control the clinical symptoms and improve pulmonary function in the treatment of AR; this approach can regulate the levels of IFN-γ and IL-4 towards the normal range in AR patients; it can also improve patient’s sleep quality. This method can produce more significant efficacy than fluticasone propionate nasal spray used alone.

Effect of 18-β Glycyrrhetinic Acid on the Endoplasmic Reticulum of Nasal Epithelial Cells in Allergic Rhinitis Model Rats / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To explore the effect of 18-β glycyrrhetinic acid (GA) on the endoplasmic reticulum of nasal epithelial cells in allergic rhinitis (AR) model rats.</p><p><b>METHODS</b>Totally 96 Wistar rats were randomly divided into the blank group, the AR model group, the loratadine group, the GA group, 24 in each group. AR models were established by peritoneally injecting ovalbumin (OVA). Morphological scoring was performed. GA at 21. 6 mg/kg was intragastrically administered to rats in the GA group. Nasal mucosal tissues were taken for electron microscopic examinations at the second, fourth, sixth, and tenth week after drug intervention.</p><p><b>RESULTS</b>The overlapping score was 2.10 ± 0.45 in the blank group, 5.10 ± 0.56 in the loratadine group, 5.10 ± 0.56 in the AR model group, 5.20 ± 0.78 in the GA group, showing statistical difference when compared with the blank group (P < 0.01). Results under transmission electron microscope showed that the number of the endoplasmic reticulum increased in the AR model group, with obvious cystic dilatation, a lot of vacuole formation, and degranulation. A large number of free ribosomes could be seen in cytoplasm. With persistent allergen exposure, changes mentioned above was progressively aggravated in the endoplasmic reticulum of nasal mucosal epithelium in the AR model group. But the dilation of endoplasmic reticulum, vacuole formation, and degranulation were relieved in the GA group, and got close to those of the blank group.</p><p><b>CONCLUSION</b>18-β GA could improve the expansion, vacuolization, and degranulation of the endoplasmic reticulum of nasal epithelial cells in AR model rats.</p>

Ten-year survey on oncology publications from China and other top-ranking countries / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Cancer is a global disease that knows no borders. Over the past decade, oncology research had developed rapidly worldwide. The aim of this study was to evaluate the publication characteristics in oncology journals from China and other top-ranking countries.</p><p><b>METHODS</b>The present study was designed to study publication characteristics in oncology journals from China and other top-ranking countries, the United States (USA), Japan, Germany, the United Kingdom (UK) and France, from 2001 to 2010. We also examined the research output from the three different regions of China: the mainland of China, Hong Kong and Taiwan.</p><p><b>RESULTS</b>Articles published in 163 journals related to oncology were retrieved from the PubMed database. The number of articles showed significantly positive trends for the six countries. The percentage of articles in the world output showed a significantly positive increase in contributions from China, especially the mainland of China. China contributed 4.5% of the total 163 journals, and 2.5% of the journals with the top 10% impact factor (IF) scores. USA contributed 31.4% of the total world output, 40.5% of the top 10% IF score journals and ranked the first.</p><p><b>CONCLUSIONS</b>This analysis described the research output from each country and region of China, and revealed the positive trend in China during 2001 and 2010. Also, by contrast with other top-ranking countries, these results imply that China falls behind the others in conducting high-quality oncology research.</p>