Research summary of chemical constituents and pharmacological effects of Panax notoginseng and predictive analysis on its Q-markers / 中国中药杂志

Panax notoginseng contains triterpene saponins, flavonoids, amino acids, polysaccharides, volatile oil and other active components, which have the effects of promoting blood circulation, stopping bleeding, removing blood stasis, etc. This study summarized the herbal research, chemical constituents and main pharmacological activities of P. notoginseng, and based on the theory of Q-markers of traditional Chinese medicine, predicted and analyzed the Q-markers of P. notoginseng from the aspects of plant kinship, efficacy, drug properties, measurability of chemical components, etc. It was found that ginsenosides Rg_1, Re, and Rb_1 with specific content ratio, ginsenosides Rb_2, Rb_3, Rc, Rd, Rh_2, and Rg_3, notoginseng R_1, dencichine and quercetin could be used as potential Q-markers of P. notoginseng, which facilitated the formulation of quality standards reflecting the efficacy of P. notoginseng.

Epidemiological Survey of Hemoglobinopathies Based on Next-Generation Sequencing Platform in Hunan Province, China / 生物医学与环境科学（英文）

OBJECTIVE@#This study was aimed at investigating the carrier rate of, and molecular variation in, α- and β-globin gene mutations in Hunan Province.@*METHODS@#We recruited 25,946 individuals attending premarital screening from 42 districts and counties in all 14 cities of Hunan Province. Hematological screening was performed, and molecular parameters were assessed.@*RESULTS@#The overall carrier rate of thalassemia was 7.1%, including 4.83% for α-thalassemia, 2.15% for β-thalassemia, and 0.12% for both α- and β-thalassemia. The highest carrier rate of thalassemia was in Yongzhou (14.57%). The most abundant genotype of α-thalassemia and β-thalassemia was -α 3.7/αα (50.23%) and β IVS-II-654/β N (28.23%), respectively. Four α-globin mutations [CD108 (ACC>AAC), CAP +29 (G>C), Hb Agrinio and Hb Cervantes] and six β-globin mutations [CAP +8 (C>T), IVS-II-848 (C>T), -56 (G>C), beta nt-77 (G>C), codon 20/21 (-TGGA) and Hb Knossos] had not previously been identified in China. Furthermore, this study provides the first report of the carrier rates of abnormal hemoglobin variants and α-globin triplication in Hunan Province, which were 0.49% and 1.99%, respectively.@*CONCLUSION@#Our study demonstrates the high complexity and diversity of thalassemia gene mutations in the Hunan population. The results should facilitate genetic counselling and the prevention of severe thalassemia in this region.

Summary of the First Meeting of the Seventh Editorial Board of Chinese Journal of Neurology / 中华神经科杂志

The First Meeting of the Seventh Editorial Committee of Chinese Journal of Neurology was held in Zhuhai, Guangdong,China on September 23, 2021. At the meeting, the list of the Seventh Editorial Board and the list of consultants were announced, the work of the magazine in the past 4 years was summarized, and the future work of the editorial board was planned and discussed. Bao Yalin, editor of the Journal Management Department of Chinese Medical Association, Liu Bing, vice president of the Chinese Medical Journals Publishing House Co., Ltd, Professor Pu Chuanqiang, editor-in-chief of the Seventh Editorial Board of Chinese Journal of Neurology, and Professor Cui Liying, honorary editor-in-chief of the Seventh Editorial Board of Chinese Journal of Neurology, attended the meeting. Totally about 100 editorial board members attended the meeting offline or online. All staff of the Editorial Department of Chinese Journal of Neurology also attended the meeting. The meeting came to a successful conclusion.

Dendrobium nobile protects against ovalbumin-induced allergic rhinitis by regulating intestinal flora and suppressing lung inflammation / 中国天然药物

Antibiotic exposure-induced dysbiosis of the intestinal flora increases the risk of developing allergic rhinitis. Hence, regulating the balance of intestinal flora may be useful for preventing and treating allergic rhinitis. However, the underlying mechanism is unclear. Dendrobium nobile (Shihu) exhibits anti-inflammatory and immune activities. Hence, in this study, we investigated the mechanism via which Shihu may improve allergic rhinitis. Mouse models of allergic rhinitis with intestinal flora dysbiosis (Model-D, antibiotics induce intestinal flora dysbiosis with ovalbumin-induced allergy) and normal intestinal flora with allergic rhinitis (Model-N, ovalbumin-induced allergy) were established. The effect of Shihu on intestinal flora and inflammation caused during allergic rhinitis were analyzed. Allergic symptoms, infiltration of hematoxylin and eosin in the lungs and nose, and the release of various factors [interleukin (IL)-2, IL-4, IFN-γ, IL-6, IL-10, and IL-17] in the lungs were evaluated. The results indicate that intestinal flora dysbiosis exacerbated lung and nose inflammation in allergic rhinitis. However, treatment with the Shihu extract effectively reversed these symptoms. Besides, the Shihu extract inhibited the PI3K/AKT/mTOR pathway and increased the level of Forkhead box protein in the lungs. Additionally, the Shihu extract reversed intestinal flora dysbiosis at the phylum and genus levels and improved regulator T cell differentiation. Furthermore, in the Model-D group, the Shihu extract inhibited the decrease in the diversity and abundance of the intestinal flora. Screening was performed to determine which intestinal flora was positively correlated with Treg differentiation using Spearman's correlation analysis. In conclusion, we showed that Shihu extract restored the balance in intestinal flora and ameliorated inflammation in the lungs of allergic rhinitis mice and predicted a therapeutic new approach using Traditional Chinese Medicine to improve allergic rhinitis.

Drug therapy and monitoring for inflammatory bowel disease: a multinational questionnaire investigation in Asia

Background/Aims@#The incidence and prevalence of inflammatory bowel disease (IBD) is rising in Asia recently. The study aimed to obtain a comprehensive understanding of the current status of drug therapy and monitoring for IBD in Asia. @*Methods@#A questionnaire investigation on drug therapy and monitoring for IBD was conducted right before the 6th Annual Meeting of Asian Organization for Crohn’s & Colitis. Questionnaires were provided to Asian physicians to fill out via emails between March and May 2018. @*Results@#In total, responses of 166 physicians from 129 medical centers were included for analysis. Among the surveyed regions, the most average number of IBD specialist gastroenterologists and nurses was 4.8 per center in Taiwan and 2.5 per center in Mainland China, respectively. 5-Aminosalicylic acid/sulfasalazine (99.4%) was the most preferred first-line choice for mild-moderate ulcerative colitis (UC), meanwhile corticosteroid (83.7%) was widely applied for severe UC. The first-line medication for Crohn’s disease (CD) markedly varied as corticosteroid (68.1%) was the most favored in Mainland China, Japan, and South Korea, followed by infliximab (52.4%) and azathioprine (47.0%). Step-up strategy was preferred in mild-moderate UC (96.4%), while 51.8% of the physicians selected top-down treatment for CD. Only 25.9% and 17.5% of the physicians could test blood concentration of infliximab and antibody to infliximab in their hospitals, respectively. @*Conclusions@#The current status of drug therapy and monitoring for IBD in Asia possesses commonalities as well as differences. Asian recommendations, IBD specialist teams and practice of therapeutic drug monitoring are required to improve IBD management in Asia.

Chinese consensus on diagnosis and treatment of intestinal Beh?et′s disease / 中华消化杂志

Beh?et′s syndrome is a kind of chronic systemic vasculitis with involvement of multiple organs. Intestinal involvement of Beh?et′s syndrome is presently named as intestinal Beh?et′s syndrome. Recently, there is considering another kind of disease type with only typical intestinal ulcers. Since it is difficult to differentiate intestinal Beh?et′s syndrome from Crohn′s disease, intestinal tuberculosis, intestinal lymphoma, and intestinal manifestations of many other autoimmune diseases, and there is limited evidence for the therapy of intestinal Beh?et′s syndrome, proposing diagnosis and treatment recommendations for intestinal Beh?et′s syndrome through evidence-based judgment will be of great significance for clinical practice.

Determination of Azide Ions in Blood by Pentafluorobenzyl Derivation Followed by GC-MS / 法医学杂志

Objective To establish a method for determination of the azide ions in blood by gas chromatography-mass spectrometry （GC-MS） following pentafluorobenzyl derivatization. Methods A blood sample of 0.2 mL was placed into a 10 mL glass test tube, and the internal standard sodium cyanide, derivatization reagent pentafluorobenzyl bromide and catalyst tetradecyl benzyl dimethyl ammonium chloride were added in turn. After vortex mixing, the mixture was heated with low-power microwave for 3 min. After centrifugation, the organic phase was taken for GC-MS analysis. Results The azide ions in blood had a good linear relationship in the mass concentration range of 0.5 to 20 μg/mL. The lowest detection limit was 0.25 μg/mL and the relative recovery was 91.36%-94.58%. The method was successfully applied to a case of death from sodium azide poisoning. The mass concentration of azide ions in the blood of the dead was 11.11 μg/mL. Conclusion The method developed in this paper has strong specificity and is easy to operate, which is suitable for the rapid detection of azide ions in blood.

Herbal textual research on Chuanxiong Rhizoma in Chinese classical prescriptions / 中国中药杂志

Fourteen classical prescriptions in the Catalog of 100 Ancient Classical Prescriptions(First Batch) promulgated in 2018 contain Chuanxiong Rhizoma, which reveals the high medicinal value and wide application of Chuanxiong Rhizoma. This paper systematically reviews the ancient herbal books and modern literature to explore the name, origin, genuine producing area, medicinal part, harvesting, and processing of Chuanxiong Rhizoma, thus facilitating the development of classical prescriptions containing Chuan-xiong Rhizoma. It is confirmed that Chuanxiong Rhizoma, formerly known as "Xiongqiong" in Chinese, was first called "Chuanxiong" in late Tang Dynasty, which has been gradually accepted as its official name due to the rise of the status of Chuanxiong Rhizoma produced in Sichuan. The main original plant of Chuanxiong Rhizoma in past dynasties has always been deemed to be Ligusticum chuan-xiong(Umbellifera), whose rhizome serves as the medicinal part. In general, it is best harvested in summer but the harvesting time can vary with different growth environments. Since the Song Dynasty, Sichuan province has been recognized as the genuine producing area of Chuanxiong Rhizoma in light of the high yield and good quality. It is suggested that Chuanxiong Rhizoma from Sichuan be used preferentially in the development of classical prescriptions. There are multiple processing methods of Chuanxiong Rhizoma recorded in ancient medical classics, and the raw(after purifying and slicing) or wine-processed or stir-fried Chuanxiong Rhizoma is still in use today. In the development of classical prescriptions containing Chuanxiong Rhizoma, Chuanxiong Rhizoma is advised to be processed in accordance with current processing standards if the specific processing method is described in the medical classics. If not, the raw Chuanxiong Rhizoma is preferred and then processed following the processing standards of Chuanxiong Rhizoma decoction pieces in Chinese Pharmacopoeia.

Analysis of Thalassemia Gene Carriers in 19 482 Pregnant Women from 2015 to 2019 in Guilin, Guangxi / 中国实验血液学杂志

OBJECTIVE@#To investigate the types and frequencies of thalassemia genes carried by the pregnant women in Guilin, Guangxi Zhuang Autonomous Region, China.@*METHODS@#From January 2015 to December 2019, blood samples of the pregnant women who visited the Outpatients of Obstetrics clinic and Eugenics Genetic clinic in Affiliated Hospital of Guilin Medical University were collected. Gap-PCR was used to detect deletional α-thalassemia, PCR-RDB to detect the gene mutations of non-deletional α-thalassemia and β-thalassemia, and MLPA or DNA sequencing to detect rare thalassemia mutations. Different types and frequencies of thalassemia mutations carried by pregnant women were analyzed statistically.@*RESULTS@#A total of 19 482 blood samples were collected, including 3 801 thalassemia gene carriers (19.51%). Seven types of α-thalassemia gene mutation were detected with a carrier rate of 15.43%. Among them, --@*CONCLUSION@#Guilin is a high-risk area for thalassemia. Alpha-thalassemia is dominated by --

Effects of electroacupuncture on cognitive function and neuronal autophagy in rats with D-galactose induced Alzheimer's disease / 针刺研究

OBJECTIVE: To observe the effect of electroacupuncture at "Baihui"(GV20) and "Shenshu"(BL23) on the expression of autophagy-related proteins in the hippocampus of rats with Alzheimer's disease (AD)，so as to explore its underlying mechanisms on improvement of AD. METHODS: Forty-eight male SD rats were randomly divided into blank control group, model group, electroacupuncture group and sham electroacupuncture group, with 12 rats in each group. The AD rat model was establish by intraperitoneal injection of D-galactose for 6 weeks. Rats in the electroacupuncture group received electroacupuncture (50 Hz, 1 mA)at GV20 and BL23 for 20 min each time after daily intraperitoneal injection. Rats in the sham electroacupuncture group received acupuncture at the local skin of GV20 and BL23 without electricity. After the intervention, Morris water maze and open field test were used to evaluate the learning and cognitive ability of rats in each group. The transmission electron microscope was used to observe the numerical density of synaptic in hippocampus, and the immunohistochemical staining was used to observe the paired helical filament protein-1 (PHF-1) in the hippocampus. Western blot was used to detected the expression of autophagy-related proteins phosphoinositide-3-kinase (PI3K), protein kinase B (AKT), phosphorylated AKT (p-AKT), mammalian target of rapamycin (mTOR) in the hippocampus. RESULTS: Compared with the blank control group, the escape latency of the rats in the model group increased from day 2 to day 5 (P<0.01), and the ratio of the time through the quadrant of the original platform reduced （P<0.01）, in the open field test the distance of exercise, the number of uprights and the rate of exercise time in the central area decreased (P<0.01), meanwhile the density of hippocampus synapses decreased (P<0.01), the positive expression of PHF-1 and the relative expression of PI3K, AKT, p-AKT, and mTOR all increased (P<0.01). Compared with the model group, the escape latency of rats in the electroacupuncture group was shortened from day 2 to day 5 (P<0.01), and the ratio of the time through the quadrant of the original platform meanwhile, the distance of the open field test, the number of uprights, and the rate of central area exercise time up-regulated (P<0.01), the numerical density of hippocampus synatic increased (P<0.01), the positive expression of PHF-1 and the relative expression of PI3K, AKT, p-AKT, and mTOR all down-regulated (P<0.01). Compared with the model group, the expression of PI3K in the sham electroacupuncture group decreased (P<0.05). CONCLUSION: Electroacupuncture can improve learning and memory and cognitive impairment in AD rats, which may be associated with its effects in regulation of hippocampal autophagy and removal of neurofibrillary tangles by suppressing PI3K/AKT/mTOR signaling pathway.

Mechanisms and Therapeutic Effects of Human Olfactory Mucosa-Derived Mesenchymal Stem Cells on Experimental Autoimmune Encephalomyelitis in Mice / 中山大学学报(医学科学版)

@#【Objective】 To study the mechanisms and therapeutic effects of human olfactory mucosa-derived mesenchymal stem cells（OMSC）on experimental autoimmune encephalomyelitis（EAE）in mice.【Methods】Under local anesthesia by using nasal endoscopy，olfactory epithelia of healthy donors were obtained，digested and cultured up to the 5th passage. OMSC were identified，differentiated and stained. EAE models were induced in C57 female mice by myelin oligodendrocyte glycoprotein（MOG35- 55）and pertussis toxin（PT）. Neurological function was documented daily. On day 16 after immunization（peak of incidence），the mice were divided randomly into two groups and treated with OMSC and PBS via tail vein injection respectively. On day 24 after immunization ，blood was collected from angular vein and levels of IL-10，IL-17，IFN-γ and IL-6 were determined by cytometric beads array（CBA）. The size of the spinal cord lesion in mice was observed and measured by using HE and LFB staining. Peripheral blood lymphocytes（PBL）of healthy donors were obtained and then co-cultured with OMSC. The proportions of CD4+ T cells secreting IFN- γ（Th1 cells）in lymphocyte group and co-culture group were compared after 2 days of cultivation. Adding IDO or COX pathway inhibitor to co- culture group and cultivating for 2 days，we observed and compared the proportions of Th1 cells in lymphocyte group，co-culture group and inhibitor treatment group respectively.【Results】OMSC exhibited certain mesenchymal stem cell-like characteristics with respect to expression of stem cell surface markers and multilineage differentiation potentials. After induced by MOG35- 55 and PT，EAE models showed different levels of neurological damage. Compared with those in PBS treatment group，in OMSC treatment group，the severity of neural dysfunction in mice was significantly reduced（P =0.002），the level of IFN-γ in serum was lower（P = 0.032），but no significant differences in the levels of IL-10，IL-17 and IL-6 were found between two groups. HE and LFB staining revealed that the inflammatory infiltration and demyelinating areas in OMSC treatment group were less than those in PBS treatment group. The proportion of Th1 cells was lower in co-culture group than that in lymphocyte group（P = 0.001），higher in IDO inhibitor group than that in co-culture group（P = 0.01），but no significant difference was found between IDO inhibitor group and lymphocyte group or between COX inhibitor group and co-culture group.【Conclusions】OMSC may regulate the proportion of Th1 lymphocytes through IDO pathway so as to inhibit the demyelinating injuries of EAE in mice. This study provides a new idea for the clinical treatment of multiple sclerosis.

Evaluation of medium to long term efficacy of balloon dilation in the treatment of aural fullness as chief complaint / 中华耳鼻咽喉头颈外科杂志

To discuss the characteristics of symptoms improvement based on the follow-up evaluation of Eustachian tube balloon dilation medium to long-term efficacy in patients with symptomatic Eustachian tube dysfunction (SETD). Patients from 2015 to 2017 were followed up after Eustachian tube balloon dilation (with the sense of aural fullness, or tinnitus and hearing ambiguity). All participants had been done ETDQ-7 before surgery and were re-evaluated with ETDQ-7 in follow-up. The improvement of overall and individual symptoms scores in ETDQ-7, the effects of gender and the difference of scores at different stages (12-18 months, 18-24 months and 24-30 months) after the operation were analyzed. There were 29 patients, including 16 males and 13 females, whose age ranged from 20 to 62 years old. The medium to long-term score of ETDQ-7 significantly declined after surgery (27.0±7.9 . 14.1±7.5, 0.05). Among all symptoms, symptoms like "blockage feeling in ear or being like under the water, constriction feeling" , "sound of blisters or explosions in the ear" decreased obviously (0.05). Comparing different stages after surgery, the scores of ETDQ-7 existed no difference (0.05). And the difference of gender showed no significant influence on surgery effects. The subjective symptoms of patients with Eustachian tube dysfunction diagnosed with SETD can be significantly improved in the medium to long-term follow-up after Eustachian tube balloon dilation, and the degree of improvement is not linearly related to the postoperative time.

Anti-leucine-rich glioma-inactivated protein 1 and glutamic acid decarboxylase 65 antibodies double-positive autoimmune encephalitis complicated with vitiligo: a case report / 中华神经科杂志

Autoimmune encephalitis (AE) refers to a kind of encephalitis mediated by immune mechanism, which is one of adult symptomatic epilepsy due to unknown etiology. Early recognition has certain difficulty. AE patients with multiple antineuronal antibody co-existing are relatively rare. Clinical symptoms are more complex and variable, and can involve a wider range of immune system. A case of temporal lobe epilepsy with anti-leucine-rich glioma-inactivated protein 1 and glutamic acid decarboxylase 65 antibodies double-positive AE complicated by vitiligo and diabetes is reported. After immune shock and continuous immunotherapy, the patient completely recovered from encephalitis and diabetes, and vitiligo was improved obviously.

Rehabilitation for Coronavirus Disease 2019: A Preliminary Discussion / 中国康复理论与实践

Rehabilitation can play an important role in the multidisciplinary management of corona virus disease 2019 (COVID-19). After a brief introduction of the epidemiology, clinical characteristics, diagnosis and treatment of the disease, this article discussed the use of physical agents, respiratory rehabilitation, intensive care rehabilitation, activities of daily living training, psychological intervention, home rehabilitation and rehabilitation of Traditional Chinese Medicine in the management of COVID-19.

Identification of Tiletamine, Zolazepam and Their Metabolites in Drug Facilitated Sexual Assault by GC-QTOF-MS / 法医学杂志

Objective To identify tiletamine, zolazepam and their metabolites in samples from drug facilitated sexual assault by gas chromatography-quadrupole time of flight mass spectrometry （GC-QTOF-MS）. Methods Urine samples of victims were collected, and detected by GC-QTOF-MS after liquid-liquid extraction and concentration. The molecular formula of fragments ions was identified by determination of accurate mass numbers, to detect related substances. Results Tiletamine, zolazepam, three metabolites of tiletamine and two metabolites of zolazepam were identified in urine samples from actual cases. Conclusion GC-QTOF-MS provides abundant and accurate information of fragment ions mass numbers, which can be used for qualitative identification of tiletamine, zolazepam and their metabolites in drug facilitated sexual assault.

Effects of Mesenchymal Stem Cells on Proliferation and Immunomodulation of B Cells / 中山大学学报(医学科学版)

@#【Objective】To study the effect of mesenchymal stem cells（MSC）on proliferation and immunomodulation of B cells in vitro.【Methods】Bone marrow 30 mL from healthy donors was isolated by density gradient centrifugation. Isolated MSC were cultivated adherently with L- DMEM medium containing 10% fetal bovine serum（FBS）. Phenotype and differentiation capacity of MSC was detected after the sixth passage. Peripheral blood mononuclear cells（PBMC）of healthy donors were also obtained by density gradient centrifugation. CD19+ B cells were sorted by fluorescence activated and co-cultured with MSC（CD19+ B∶MSC = 5∶1）group. Stimulated by CpG+ CD40L，the proliferation of B cells of two groups were checked 96 hours after co-culture respectively. The CD19+CD5+ B cells percentage and its secretion of IL-10 were detected by FACS. The effects of CD19+ B cells on the proliferation of CD4+ T cells and the secretion of IFN-γ were continually observed. Anti-IL-10 was used to confirm the effect of B cells on proliferation and IFN-γ secretion of CD4+ T cells.【Results】MSC collected from healthy donors remained differentiation capacity. MSC derived from bone marrow expressed CD29，CD44，CD73，CD90，CD105，and CD166，but did not express CD45 and CD34. Compared with control group，the proportion of CD19+ B cells proliferation in co-cultured group was significantly increased after 3 days，meanwhile，the level of IFN-γ，which secreted by CD4+ T cells was significantly restrained. To make a further analysis of the subsets of CD19+ B cells，the percentage of CD5+ B cells in co-cultured group increased from（21.31±1.22）% to（31.27±0.92）%（P=0.014），and its IL-10 secretion increased from（1.09±0.08）% to（2.44±0.06）%（P<0.001）compared with control group. After anti-IL-10 was used，the B cells co-cultured with MSC showed a decreased capacity of inhibiting the proliferation and IFN-γ secretion of CD4+ T cells.【Conclusions】MSC could promote the proliferation of CD19+ B cells to inhibit the secretion of IFN-γ by CD4+ T cells，which may be related to the increasing expression of IL-10 by CD19+CD5+B cells.

A Prospective Randomized Multicenter Controlled Trial on Salvianolate for Treatment of Unstable Angina Pectoris in A Chinese Elderly Population / 中国结合医学杂志

OBJECTIVE@#To evaluate the efficacy and safety of salvianolate in elderly patients with unstable angina pectoris (UAP).@*METHODS@#A prospective double-blind randomized placebo-controlled multicenter trial in elderly patients with UAP from 13 third-grade class-A hospitals in China was performed. A total of 318 patients were randomly allocated in a 1:1 ratio to an experimental group (160 patients) and a control group (158 patients). The experimental group was treated with salvianolate for 14 days on the basis of conventional medicine, and the control group was given a placebo for 14 days with the same criteria. Follow-up was lasted 28 days in both groups. The primary endpoint was biweekly frequency of angina pectoris attacks. The secondary endpoints included biweekly dosage of nitroglycerin, the Seattle Angina Questionnaire, angina pectoris severity and duration, myocardial injury markers, high-sensitivity C-reactive protein (hs-CRP) and N-terminal pro-B-type natriuretic peptide (NT-proBNP), as well as major adverse cardiovascular events (MACEs). Safety was assessed according to adverse events and serious adverse events.@*RESULTS@#Baseline characteristics were similar between treatment groups. Compared with those in the control group, the frequency of biweekly angina attacks (2.92 vs . 4.08, P=0.025), the biweekly dosage of nitroglycerin, as well as the severity and duration of angina attacks (P<0.01) were reduced by salvianolate. The Seattle Angina Questionnaire score was also significantly improved in the experimental group than in the control group (P<0.05). No significant differences were observed between the two groups with respect to the incidence of MACEs. Salvianolate was well tolerated.@*CONCLUSIONS@#Salvianolate appear to have efficacy and well tolerated for elderly patients with UAP. [ClinicalTrials.gov identifier: NCT03037047].

Predictive value of the combination of infliximab trough levels and C reactive protein in secondary loss of response to infliximab after induced remission / 中华消化杂志

Objective To evaluate the role of infliximab trough levels(IFX-TL)and C reactive protein(CRP)concentration in prediction secondary loss of response(LOR)to infliximab(IFX)in patients with Crohn′s disease(CD)during IFX maintenance therapy since 14 weeks after induced treatment.Methods From November 2015 to October 2016,43 CD patients received IFX treatment were enrolled.IFX was initially given at zero,two,and six weeks at 5 mg/kg as induced therapy,and then the same dose was given every eight weeks as long-term maintenance treatment.Serum IFX-TL and CRP concentration were measured at 14thweek after the first IFX injection.The disease activity of CD was assessed by the Harvey-Braddshaw index.According to the follow-up results,the enrolled patients were divided into LOR group and continuous response group,and then the differences in IFX-TL and CRP concentrations at the 14thweek after induced therapy were compared between two groups.Mann-Whitney U test and receiver operating characteristic(ROC)curve were performed for statistical analysis.Results After a median 54 weeks of follow-up,18(41.9%)of 43 CD patients achieved a sustained response to IFX therapy,while 11 patients(25.6%)were LOR to IFX therapy.At the 14thweek after induced therapy,serum IFX-TL of LOR group was 2.30 μg/mL(0.52 μg/mL,2.92 μg/mL),which was lower than that of continuous response group(5.10 μg/mL(3.54 μg/mL,9.34 μg/mL)),and the difference was statistically significant(Z= -3.236,P=0.001).The CRP concentration of LOR group was 3.10 mg/L (0.38 mg/L,21.70 mg/L),which was higher than that of continuous response group(0.51 mg/L(0.27 mg/L, 1.50 mg/L)),and the difference was statistically significant(Z= -1.732,P=0.015).The results of ROC curve analysis indicated that at 14thweek after induced therapy the area under curve(AUC)value of predictive role of serum IFX-TL and CRP level in LOR to IFX was 0.864(95% confidence interval(CI)0.728 to 0.999),sensitivities were 83.3% and 81.8%,specificities were 94.4% and 54.5%,cut-off values of accuracies were 3.115 μg/mL and 5.93 mg/L.Conclusion IFX-TL<3.115 μg/mL and CRP concentration>5.93 mg/L at 14thweek since IFX induced therapy might be used as effective predictors of LOR in CD patients during maintenance therapy.

Effects of Adipose-derived Mesenchymal Stem Cell Exosomes on Corneal Stromal Fibroblast Viability and Extracellular Matrix Synthesis / 中华医学杂志(英文版)

<p><b>Background</b>Corneal stromal cells (CSCs) are components of the corneal endothelial microenvironment that can be induced to form a functional tissue-engineered corneal endothelium. Adipose-derived mesenchymal stem cells (ADSCs) have been reported as an important component of regenerative medicine and cell therapy for corneal stromal damage. We have demonstrated that the treatment with ADSCs leads to phenotypic changes in CSCs in vitro. However, the underlying mechanisms of such ADSC-induced changes in CSCs remain unclear.</p><p><b>Methods</b>ADSCs and CSCs were isolated from New Zealand white rabbits and cultured in vitro. An Exosome Isolation Kit, Western blotting, and nanoparticle tracking analysis (NTA) were used to isolate and confirm the exosomes from ADSC culture medium. Meanwhile, the optimal exosome concentration and treatment time were selected. Cell Counting Kit-8 and annexin V-fluorescein isothiocyanate/propidium iodide assays were used to assess the effect of ADSC- derived exosomes on the proliferation and apoptosis of CSCs. To evaluate the effects of ADSC- derived exosomes on CSC invasion activity, Western blotting was used to detect the expression of matrix metalloproteinases (MMPs) and collagens.</p><p><b>Results:</b>ADSCs and CSCs were successfully isolated from New Zealand rabbits. The optimal concentration and treatment time of exosomes for the following study were 100 μg/ml and 96 h, respectively. NTA revealed that the ADSC-derived exosomes appeared as nanoparticles (40-200 nm), and Western blotting confirmed positive expression of CD9, CD81, flotillin-1, and HSP70 versus ADSC cytoplasmic proteins (all P < 0.01). ADSC-derived exosomes (50 μg/ml and 100 μg/ml) significantly promoted proliferation and inhibited apoptosis (mainly early apoptosis) of CSCs versus non-exosome-treated CSCs (all P < 0.05). Interestingly, MMPs were downregulated and extracellular matrix (ECM)-related proteins including collagens and fibronectin were upregulated in the exosome-treated CSCs versus non-exosome-treated CSCs (MMP1: t = 80.103, P < 0.01; MMP2: t = 114.778, P < 0.01; MMP3: t = 56.208, P < 0.01; and MMP9: t = 60.617, P < 0.01; collagen I: t = -82.742, P < 0.01; collagen II: t = -72.818, P < 0.01; collagen III: t = -104.452, P < 0.01; collagen IV: t = -133.426, P < 0.01, and collagen V: t = -294.019, P < 0.01; and fibronectin: t = -92.491, P < 0.01, respectively).</p><p><b>Conclusion:</b>The findings indicate that ADSCs might play an important role in CSC viability regulation and ECM remodeling, partially through the secretion of exosomes.</p>

Tick-Borne Pathogens in Ixodid Ticks from Poyang Lake Region, Southeastern China

Ticks are the vectors of various pathogens, threatening human health and animal production across the globe. Here, for the first time we detected Ricketssia spp., Borrelia spp. and protozoan in ticks from Poyang Lake region in Jiangxi Province of eastern China. In 3 habitat categories and on 12 host species, 311 ticks from 11 species were collected. Haemaphysalis longicornis was the predominant species, accounting for 55.63%, followed by Rhipicephalus microplus, Haemaphysalis flava and Ixodes granulatus. Of the collected ticks, 7.07% were positive for tick-borne pathogens, and H. longicornis and H. flava were found to be co-infected with Ricketssia spp. and protozoan. H. flava was the most detected positive for tick-borne pathogens, whereas H. longicornis had the lowest infection rate, and the difference in infection rates between tick species was significant (χ²=61.24, P < 0.001). Furthermore, adult ticks demonstrated remarkably greater infection rate than immature ticks (χ²=10.12, P=0.018), meanwhile ticks on Erinaceidae showed significantly higher positivity than ticks collected on other host species (χ²=108.44, P < 0.001). Genetic fragment sequencing and analyses showed at least 4 pathogen species presence in ticks, namely Borrelia yangtzensis, Rickettsia slovaca or Rickettsia raoultii related genospecies, Babesia vogeli and Hepatozoon canis or Hepatozoon felis related genospecies. The finding indicates that the abundant ticks can carry diverse pathogens in Poyang Lake region, and pathogen infection is highly related to species, vertebrate hosts and life stages of ticks.