Relationship between rs128912 single nucleotide polymorphism in promoter region of Toll-like receptor 3 gene and cataract in Chinese Han population / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To analyze the relationship between rs128912 single nucleotide polymorphism(SNP)in the promoter region of Toll-like receptor 3(TLR3)gene and cataract in Chinese Han population.METHODS: A total of 263 patients with cataract admitted to our hospital from June 2019 to June 2021 were selected as study group, and 150 patients with lens dislocation were included in control group. Western blotting was used to detect the expression of TLR3 protein in the anterior capsular tissues of lens in the two groups, and direct sequencing method was applied to analyze the polymorphism of rs128912 locus in the promoter region of TLR3 gene. The expression of peripheral blood TLR3 mRNA of patients with different genotypes was detected by real-time quantitative polymerase chain reaction(RT-qPCR).RESULTS: The expression level of TLR3 protein in the anterior capsular tissues in the study group was higher than that in the control group(P<0.05). The frequencies of genotypes(AA, AT, TT)at rs128912 locus in the TLR3 gene promoter region in the study group and the control group were in accordance with Hardy-Weinberg genetic equilibrium, and there were differences in the frequencies of genotypes(AA, AT, TT)and frequencies of alleles(A, T)at rs128912 locus in the TLR3 gene promoter region between both groups(P<0.05). The relative expression level of peripheral blood TLR3 mRNA in patients with TT genotype in the study group was higher than that in patients with AA or AT genotypes(P<0.05).CONCLUSION: The expression of TLR3 protein in anterior capsular tissues of lens of patients with cataract is significantly up-regulated, and rs128912 locus polymorphism in the TLR3 gene promoter region is related to the susceptibility of cataract in Chinese Han population, and people with TT genotype are more prone to cataract.

A long-term ischemic stroke risk score model in patients aged 60 years and older with obstructive sleep apnea: a multicenter prospective cohort study / 南方医科大学学报

OBJECTIVE@#To analyze the independent risk factors of long-term ischemic stroke and establish a nomogram for predicting the long-term risks in elderly patients with obstructive sleep apnea (OSA).@*METHODS@#This multicenter prospective cohort study was conducted from January, 2015 to October, 2017 among consecutive elderly patients (≥60 years) with newly diagnosed OSA without a history of cardio-cerebrovascular diseases and loss of important clinical indicators. The follow-up outcome was the occurrence of ischemic stroke. The baseline demographic and clinical data, sleep parameters, laboratory and ultrasound results were collected from all the patients, who were randomized into the modeling group (n=856) and validation group (n=258) at a 3∶1 ratio. LASSO regression was used for variable reduction and dimension screening, and the risk score prediction model of ischemic stroke was established based on Cox proportional hazard regression.@*RESULTS@#In the total of 1141 patients enrolled in this study, 58 (5.08%) patients experienced ischemic stroke during the median follow-up of 42 months (range 41-54 months). The cumulative incidence of ischemic stroke was 5.14% in the model group and 4.91% in the verification group (P < 0.05). Age (HR=3.44, 95% CI: 2.38- 7.77), fasting blood glucose (FPG) (HR=2.13, 95% CI: 1.22-3.72), internal diameter of the ascending aorta (HR=2.60, 95% CI: 1.0- 4.47), left atrial anteroposterior diameter (HR=1.98, 95% CI: 1.75-2.25) and minimum oxygen saturation (LSpO2) (HR=1.57, 95% CI: 1.20-1.93) were identified as independent risk factors for ischemic stroke (P < 0.05 or 0.01). A long-term ischemic stroke risk score model was constructed based the regression coefficient ratios of these 5 risk variables. Before and after the application of the Bootstrap method, the AUC of the cohort risk score model was 0.84 (95% CI: 0.78- 0.90) and 0.85 (95% CI: 0.78- 0.89) in the model group and was 0.83 (95% CI: 0.73-0.93) and 0.82 (95%CI: 0.72-0.90) in the verification group, respectively, suggesting a good prediction efficiency and high robustness of the model. At the best clinical cutoff point, the cumulative incidence of ischemic stroke was significantly higher in the high-risk group than in the low-risk group (P=0.021).@*CONCLUSION@#This model can help to identify high-risk OSA patients for early interventions of the risks of ischemic stroke associated with OSA.

The Clinical and Laboratory Characteristics of Adult Langerhans Cell Histiocytosis Patients and the Influencing Factors of Prognosis / 中国实验血液学杂志

OBJECTIVE@#To observe the clinical and laboratory characteristics of adult Langerhans cell histiocytosis(LCH) patients and to analyze the influencing factors of its prognosis.@*METHODS@#The clinical and laboratory charac-teristics of 38 adult LCH patients treated in our hospital from January 2010 to August 2019 were retrospective analyzed, and the clinical prognosis of the patients was analyzed.@*RESULTS@#The median age of 38 patients was 41 (21-65) years old, and the ratio of male and female was about 2∶1. Among 38 patients, 44.7% (17/38) were involved in multiple systems, and 31.6% (12/38) were involved in high-risk organs (including liver, lung, hematopoietic system or spleen). The bone involvement was the most common (21/38, 55.3%), and the most common clinical symptom was pain (19/38, 50.0%). The result of laboratory showed that anemia (4/38，10.5%), thrombocytopenia (1/38，2.6%), neutropenia (2/38，5.3%), lymphopenia (6/38，15.8%), monocytosis (11/38，28.9%), C-reactive protein increasing (6/21，28.6%), erythrocyte sedimentation rate increasing (10/18, 55.3%), and ferritin protein increasing (9/17, 55.3%). The median follow-up time was 53 months, and a total of 5 patients were died. The 10-year overall survival rate of patients with single-system involvement was 100%, which was significantly higher than that of patients with multiple-system involvement (70.1%) (P=0.0078). The prognosis of patients without risk-organ involvement was better than that of patients with risk-organ involvement (10-year overall survival rate: 100% vs 60.6%) (P=0.0007). Further analysis showed that in addition to multiple-system involvement and risk-organ involvement, the increase of peripheral blood monocyte cells and the increase of ferritin protein were also associated with poorer prognosis of the patients.@*CONCLUSION@#The multiple system involve-ment and risk-organ involvement, the increasing of monocyte cells and the increasing of ferritin protein were the independent risk factors of adult LCH patients.

Association of copy number of SMN1 and SMN2 with clinical phenotypes in children with spinal muscular atrophy / 中国当代儿科杂志

OBJECTIVE@#To study the association of copy number of SMN1 and SMN2 with clinical phenotypes in children with spinal muscular atrophy (SMA).@*METHODS@#A total of 45 children with SMA were enrolled. Multiplex ligation-dependent probe amplification was used to measure the gene copy numbers of SMN1 and SMN2. The association of copy number of SMN1 and SMN2 with clinical phenotypes was analyzed.@*RESULTS@#Of the 45 children with SMA, 42 (93%) had a homozygous deletion of SMN1 exons 7 and 8, and 3 (7%) had a deletion of SMN1 exon 7 alone. No association was found between SMA clinical types and the deletion types of SMN1 exons 7 and 8 (P>0.05). There was a significant difference in the distribution of SMN2 gene copy numbers between the children with SMA and the healthy children (P<0.05). The children with SMA usually had two or three copies of SMN2 gene, while the healthy children usually had one or two copies of SMN2 gene. There was a significant difference in the distribution of SMN2 copy numbers among the children with different SMA clinical types (P<0.05). The children with two copies of SMN2 gene had a significantly lower age of onset than those with three or four copies. Most of the children with type I SMA had two or three copies of SMN2 gene. Most of the children with type II SMA had three copies of SMN2 gene. Most of the children with type III SMA had three or four copies of SMN2 gene. Children with a higher copy number of SMN2 gene tended to have an older age of onset and better motor function and clinical outcome, and there was a significant association between SMN2 gene copy number and clinical outcome (P<0.05).@*CONCLUSIONS@#The SMN2 gene can reduce the severity of SMA via the dosage compensation effect. SMN2 copy number is associated with the phenotype of SMA, and therefore, it can be used to predict disease severity.

Role and mechanism of TRP ion channels in pruritus / 中国药理学通报

Pruritus is an unpleasant noxious sensation induced by a variety of causes. Although pruritus does not cause death directly, long-term chronic pruritus severely reduces the quality of life of patients. TRP (transient receptor potential ion channels) participate in the physiological process from the sensation to skin balance. A large number of studies have confirmed that many itch media are involved in signal transduction related to TRP ion channels. We review the difference between itch and pain, and the role and mechanism of TRP in itch, so as to provide new research targets for treatment of pruritus.

Quality differences between Mongolian and traditional Chinese medicine Veratri Nigri Radix et Rhizoma by HPLC fingerprint and acute toxicity / 中草药

Objective: To evaluate the quality differences between Mongolian medicine and traditional Chinese medicine (TCM) Veratri Nigri Radix et Rhizoma in HPLC fingerprint and acute toxicity, as a fundamental research for quality standazation. Methods: HPLC fingerprint methods were used to analyze the steroid alkaloids and stilbenes of Veratri Nigri Radix et Rhizoma from different origins. A total of 14 batches of crude drugs, including eight Mongolian and six TCM samples, were examined, and their common pattern were established by authoritative software "fingerprint similarity evaluation system". Characteristic peaks in these fingerprints, including 32 steroid alkaloids and 16 stilbenes, were selected to performing cluster analysis, using SPSS 20.0 software with relative peak area as variables. Through the experiments of acute toxicity in mice, their toxicities were examined. Results: HPLC fingerprint methods of steroid alkaloids and stilbenes were established for the quality evaluation of Veratri Nigri Radix et Rhizoma, and their common patterns of Mongolian medicines (RMJ, RMZ) and TCMs (RZJ, RZZ) with high similarities between groups were obtained. In clustering analysis, 14 batches of Veratri Nigri Radix et Rhizoma were divided into two categories distinctly, as Mongolian medicine and TCM groups. Mongolian medicine showed stronger toxicity than TCM with the LD50 values as 0.503 0 and 17.934 3 g/kg, respectively. Conclusion: The quality of Mongolian medicine and TCM Veratri Nigri Radix et Rhizoma in the aspects of efficacy and idications, producing area, chemical composition and acute toxicity were of significant differences. It is necessary and emergency to distinguish the two crude drugs, and establish quality standard of Mongolian medicine Veratri Nigri Radix et Rhizoma.

Overview of Taiwan's indigenous ethnopharmacology in the perspective of traditional knowledge protection / 中国结合医学杂志

Ethnopharmacology, the study of ethnic use of drugs, opens up the crucial gateway to understanding and promoting traditional medicine in the new age. Taiwan is a unique region where traditional medicine and herbal therapeutics have been benefiting its people of multiple races for centuries. This article overviews Taiwan's indigenous traditional medicine and the emerging status of ethnopharmacology study, and outlines the global scenario of the inheritance and development of traditional medicine. In such a scope of knowledge protection, this article particularly highlights the challenges with bioprospecting and biopiracy, and summarizes the current measures for protection of traditional knowledge in Taiwan. Finally, based upon these analyses, we propose rational strategies for promoting Taiwan's ethnopharmacology, from multiple angles of resource, economy, policy and law. We conclude that four measures, namely (1) protecting the natural environment of biodiversity, (2) avoiding unnecessary conflicts caused by bioprospecting and biopiracy, (3) strengthening the international collaboration, and (4) upgrading the legal system of traditional intelligence, would be the right paths for Taiwan to protect its invaluable heritage of traditional medicine and the knowledge of ethnopharmacology therein.

Localization of cAMP-response element binding protein target gene Staufen in mouse hippocampus by situ hybridization / 浙江大学学报·医学版

<p><b>OBJECTIVE</b>To search for an appropriate animal model that is more closely related to human to study cAMP-response element binding protein target gene Staufen and to identify its location.</p><p><b>METHODS</b>The phylogenetic tree was constructed with Staufen protein (STAUFEN) sequences of different species, and the most suitable animal model was selected by analyzing relativity among them. The Staufen fragments were amplified with reverse transcription-PCR and inserted into a vector and then the sub-clone was transformed into bacteria, selected, amplified, extracted and sequenced. Staufen probes were in vitro transcribed and hybridized in situ on the cryosections of the mouse brain. The cryosections were stained and observed.</p><p><b>RESULTS</b>The clustering patterns of the phylogenetic tree indicated that the mouse and human Staufen1 had 99.7% protein sequences similarity. The mRNA of Staufen was located in CA1, CA2, CA3 and DG hippocampus regions shown by in situ hybridization.</p><p><b>CONCLUSION</b>The mouse is a preferable animal model for research on Staufen transcription in hippocampus.</p>

Microbubbles targeted to P-selectin for evaluating testicular ischemia-reperfusion injury in rabbits / 中华男科学杂志

<p><b>OBJECTIVE</b>To explore the feasibility of evaluating complete ischemia-reperfusion injury (IRI) of the testis by contrast-enhanced ultrasonography with microbubbles (MB) targeted to P-selectin (MBp) in rabbits.</p><p><b>METHODS</b>We randomly divided 30 healthy adult rabbits into five groups of equal number (control, 0.5 h IRI, 1 h IRI, 2 h IRI, and 4 h IRI), prepared phospholipid MB and MBp, and performed contrast-enhanced ultrasonography of the bilateral testes with MB or MBp at an interval of 20 min at different times after IRI. When MB or MBp disappeared completely in the healthy testis at 4 to 5 min after intravenous injection, we recorded the power of the first frame (F-P) in the IRI testes followed by immunohistochemical staining of the testis tissue.</p><p><b>RESULTS</b>CEU with MBp achieved a significantly higher F-P than that with MB in all the IRI groups (P < 0.05), which was (8.34 +/- 1.20) versus (1.87 +/- 0.25) 10(-5) AU at 2 hours, but there was no significant difference between MB and MBp in the control rabbits (0 AU, P > 0.05). Immunohistochemistry showed a significantly time-dependent increase in the expression of P-selectin in the vascular endothelial cells of the IRI testes, but not in those of the control.</p><p><b>CONCLUSION</b>Contrast-enhanced ultrasonography with MBp can be used to evaluate the inflammatory reaction of testicular ischemia-reperfusion injury.</p>

Preparation of herpetrione nanosuspensions and preliminary study on its pharmacokinetics / 中国药学杂志

OBJECTIVE: To prepare herpetrione nanosuspension (PEDX-NS) and evaluate its pharmacokinetics in rats. METHODS: PEDX-NS was prepared by high pressure homogenization technology, and its morphology and mean diameter were determined. An HPLC method was employed to determine the concentration of herpetrione(PEDX), the index component of PEDX-NS, in plasma, and the bioavailability of the nanosuspension was compared with the reference formulation after oral administration in Wistar rats. RESULTS: The particles in the nanosuspension observed by scanning electron microscopy were irregular spheres, and the mean particle size of PEDX-NS was (238.6 ± 1.9)nm. Its pharmacokinetic process calculated with DAS2.0 software was fitted to a two-compartment model. The AUG was 25.19 μg · h · mL-1 and the pmax was 11.64 μg · mL-1, which were 2.47 and 2.63 times of the reference formulation, respectively (P < 0.01). CONCLUSION: It is feasible to prepare PEDX-NS by high pressure homogenization technology, and PEDX-NS can improve the bioavailability of PEDX notablely.

Effect of human placental extract on proliferation of human umbilical cord blood CD34(+) cells in vitro / 中国实验血液学杂志

The study was aimed to investigate the hematopoietic function of placenta tissue and clarify the effect of human placental chorionic tissue in different periods on proliferation of hematopoietic stem cells in vitro, in order to further understand the changes of the hematopoietic function of placenta with the time prolonging. The experiments were divided into four groups: early placenta (group B), mid-term placenta (group C), full-term placenta (group D), and blank group (group A). The hematopoietic stem cells were amplified in co-culture way, and the colony formation ability after the expansion was observed. The results showed that compared to initial concentration, the CD34(+) cells cultured with full-term placenta were amplified by (2.60 ± 0.20) times, which was significantly higher than those CD34(+) cells cultured with mid-term placenta (1.74 ± 0.24) and early placenta (1.14 ± 0.12), but that in blank group was reduced without amplification. After culture for 14 days, the colony number of group C and group D were significantly higher than that of group A and group B. Among them the number of CFU-GM, CFU-GEMM, BFU-E of group C all were a little higher than that of group D. It is concluded that human placental extract in different period without any exogenous cell factors all can support the proliferation of hematopoietic stem cells, this ability is getting stronger with time increasing. The colony formation ability of the amplified cells shows weakened after the first increase, this colony formation ability of the amplified cells in group C is strongest, slightly stronger than that of group D.

Comparison of microcalorimetric fingerprint profiles of Lonicerae japonicae Flos and Lonicerae Flos / 药学学报

To compare the microcalorimetric fingerprint profiles of Lonicerae japonicae Flos (Lj.F) and Lonicerae Flos (L.F), microcalormietry was applied to find the heat change regularity of Bacillus shigae (B. shigae) metabolism affected by Lj.F and L.F (we choose Lonicera macranthoides Hand.-Mazz in this paper) with different concentrations. The thermogenic curves and thermodynamics parameters were investigated as evaluation index, and then the date of experiment was studied by similarity analysis. All the results indicated that the Lj.F and Lonicera macranthoides Hand.-Mazz (L.m.H-M) significantly impacted the microbial growth and had good similarity in its inhibitory activities. The combination approach of chemical analysis with bioassay was developed and employed to ensure the safety and efficacy of Chinese herbal medicines.

Relationship of CD4+ CD25hi regulatory T (Treg) cells to disease progression in HIV-infected patients / 中华实验和临床病毒学杂志

<p><b>OBJECTIVE</b>Analyzing the relationships between peripheral blood CD4+ CD25hi regulatory T (Treg) cells and peripheral blood immune status or plasma HIV-lviral load in HIV-infected individuals,so as to determine whether Treg were related to the progression of HIV-infected disease.</p><p><b>METHODS</b>116 HIV-infected patients in different stages and 21 healthy control individuals were included in this study. The CD4+ and CD8+ T cell counts were determined by a standard 4-color flow cytometry technique. The Treg cells were examined with 3-color immune staining flow cytometry. The plasma HIV-1 viral load was detected by real time PCR.</p><p><b>RESULTS</b>The frequencies of Treg cells decreased in HIV-infected individuals with high CD4+ T cell counts( > 300/microl) compared with normal controls. With the progression of disease the frequencies of Treg cells were raised gradually, until were increased in HIV-infected individuals with low levels of CD4+ T cell counts ( < 100/microl). In addition, the frequencies of Treg cells were inversely related to CD4+ T cell counts and CD4+ /CD8+ ratio, data showed a statistically significant (respectively, r = -0.564, P < 0.001; r = -0.377, P < 0.001). Furthermore, the proportions of Treg cells were closely related to plasma HIV-1 RNA viral load (r = 0.514, P < 0.001).</p><p><b>CONCLUSION</b>CD4 CD25hi Treg cells should be a kind of important cells participating the immunopathogenesis of AIDS. It may play different roles in different stages of HIV-infected disease. The exact mechanism of Treg cells in the progression of the HIV-infected disease needs to be investigate further.</p>

Biomolecular mechanisms of cyclosporine A, tetrandrine and their combination on the reversion of multidrug resistance in human leukemia cell line / 中国中西医结合杂志

<p><b>OBJECTIVE</b>Multidrug resistance (MDR) plays an important role in the failure of chemotherapy on malignant tumors. This study was to investigate the biomolecular mechanisms of cyclosporine A (CsA), tetrandrine (Tet) and their combination on multidrug resistance in cell line K562/A02.</p><p><b>METHODS</b>K562/A02 cells were treated with CsA and (or) Tet. The intracellular daunorubicin (DNR) concentration and the expression of P-glycoprotein (P-gp) were observed by flow cytometry assay. The mRNA expression of mudtiding resistance gene (mdr1) was measured by fluorescent semi-quantitative reverse transcriptase polymerase chain reaction (RT-PCR).</p><p><b>RESULTS</b>CsA and Tet (alone or combination) elevated the intracellular DNR concentration in K562/A02 cells (the fluorescence intensity of intracellular DNR in K562/A02 cells was 60%, 65% and 98% respectively of that in K562 cells). The fluorescence intensity of P-gp in K562 and K562/A02 cells was 0.18% and 96.51%. The P-gp expression was down-regulated after treated with CsA, Tet and both (75.32%, 76.86% and 48.61%); mdr1 mRNA was also down-regulated, and the effect of their combination was more obvious.</p><p><b>CONCLUSION</b>MDR can be partially reversed by CsA or Tet, the combination of both drugs shows a great synergistic reversal effect.</p>

Rapid determination of optimal time for peripheral blood stem cell harvest by detecting hematopoietor progenitor cell during mobilization / 中南大学学报(医学版)

OBJECTIVE@#To develop a simple method to rapidly determine the optimal time of perpheral blood stem cell harvest.@*METHODS@#We selected 5 healthy donors mobilized with granulocyte colony-stimulating factor (G-CSF) in allogenic peripheral blood stem cell transplantation (allo-PBSCT) to continuously monitor the variety of hematopoietic stem/progenitor cells (HSC/HPC) in the peripheral blood. HPC in the peripheral blood was detected by Sysmex XE-2100 fully automated hematology analyzer with an immature myeloid information channel and the CD34+ cells and colony-forming unit-granulocyte-macrophage (CFU-GM) were determined by flow cytometry and colony culture during mobilization.@*RESULTS@#HPC was positively correlated with the CD34+ cells or CFU-GM in the peripheral blood (r = 0.82 or r = 0.85, respectively). HPC, CD34+ cells, and CFU-GM in allo-PBSCT donors obviously increased on the 4th day after the mobilization, and their peaks were on the 5th day after the mobilization. But HPC varied more than CD34+ cells and CFU-GM did.@*CONCLUSION@#Sysmex XE-2100 can rapidly monitor the variety of HSC/HPC in allo-PBSCT donors mobilizated with G-CSF, and can provide a simple and economic method to determine the optimal time of peripheral blood stem cell harvest.