Short-term effectiveness of ixekizumab in the treatment of psoriasis: a single-center retrospective study / 中华皮肤科杂志

Objective:To evaluate the real-world short-term effectiveness of ixekizumab in the treatment of psoriasis, and to investigate factors influencing the effectiveness.Methods:Baseline data and short-term effectiveness evaluation results were retrospectively collected from patients with psoriasis, who received ixekizumab treatment in Department of Dermatology, Xiangya Hospital from November 2019 to September 2021. A descriptive analysis was performed on the baseline characteristics of patients, continuous data were described as median (lower quartile, upper quartile), and categorical data were described as percentages. Comparisons of disease severity scores before and after the treatment with ixekizumab were performed using Wilcoxon signed-rank test or paired McNemar test. Multivariable logistic regression analysis was conducted to explore factors influencing the effectiveness of 4-week ixekizumab treatment.Results:A total of 118 patients with psoriasis were included, including 94 males and 24 females, and their age [ M ( Q1, Q3) ] was 43.4 (32.5, 53.0) years; plaque psoriasis (99 cases, 83.9%) and severe psoriasis (72 cases, 68.6%) predominated among the 118 patients, and skin lesions were mainly located on the scalp (59/116, 50.9%). Among the 49 patients who had received 2-week ixekizumab treatment, 27 (55.1%) achieved a 50% improvement in the psoriasis area and severity index (PASI) score (PASI50) ; after 4-week treatment, 44 (89.8%), 30 (61.2%), 13 (26.5%) and 10 (20.4%) patients achieved PASI50/75/90/100 respectively, and their PASI scores (2.1 [1.1, 7.1]), involved body surface area (3.9% [0.5%, 14.5%]), dermatology life quality index scores (1.0 [0.0, 2.0]) and physician global assessment (PGA) scores (1.0 [1.0, 3.0]) were significantly lower than the corresponding scores at baseline (12.4 [8.8, 23.2], 22.0% [11.3%, 43.4%], 6.0 [3.0, 11.0], 4.0 [3.0, 5.0], respectively; all P < 0.001]. Multivariable logistic regression analysis showed that the baseline body mass index was significantly associated with the PASI75 response rate ( OR = 0.814, 95% CI: 0.659 - 0.958, P = 0.029) and the proportion of patients with PGA0/1 ( OR = 0.743, 95% CI: 0.562 - 0.917, P = 0.017) after 4-week ixekizumab treatment, and the baseline BSA score was significantly associated with the proportion of patients with PGA0/1 after 4-week ixekizumab treatment ( OR = 0.924, 95% CI: 0.870 - 0.968, P = 0.003) . Conclusion:The 4-week ixekizumab treatment significantly decreased the severity of psoriasis, and may be more effective in patients with lower disease severity and lower body mass index at baseline.

mA Regulates Neurogenesis and Neuronal Development by Modulating Histone Methyltransferase Ezh2 / 基因组蛋白质组与生物信息学报·英文版

N-methyladenosine (mA), catalyzed by the methyltransferase complex consisting of Mettl3 and Mettl14, is the most abundant RNA modification in mRNAs and participates in diverse biological processes. However, the roles and precise mechanisms of mA modification in regulating neuronal development and adult neurogenesis remain unclear. Here, we examined the function of Mettl3, the key component of the complex, in neuronal development and adult neurogenesis of mice. We found that the depletion of Mettl3 significantly reduced mA levels in adult neural stem cells (aNSCs) and inhibited the proliferation of aNSCs. Mettl3 depletion not only inhibited neuronal development and skewed the differentiation of aNSCs more toward glial lineage, but also affected the morphological maturation of newborn neurons in the adult brain. mA immunoprecipitation combined with deep sequencing (MeRIP-seq) revealed that mA was predominantly enriched in transcripts related to neurogenesis and neuronal development. Mechanistically, mA was present on the transcripts of histone methyltransferase Ezh2, and its reduction upon Mettl3 knockdown decreased both Ezh2 protein expression and consequent H3K27me3 levels. The defects of neurogenesis and neuronal development induced by Mettl3 depletion could be rescued by Ezh2 overexpression. Collectively, our results uncover a crosstalk between RNA and histone modifications and indicate that Mettl3-mediated mA modification plays an important role in regulating neurogenesis and neuronal development through modulating Ezh2.

Experimental study on improvement of blood supply timeliness of rabbits with vertebral artery type of cervical spondylosis by massage / 中国骨伤

<p><b>OBJECTIVE</b>Establishing a rabbit model of vertebral artery type of cervical spondylosis(CSA) and to observe the characteristics of timeliness in improving the blood flow of vertebral artery by massage, and discusse the material basis of this timeliness based on NPY and ET-1.</p><p><b>METHODS</b>Fifty New Zealand healthy and white rabbits, 6-month-old, the body mass of (2.0±0.5) kg, with half males and half females, were randomly divided into blank group, model group, three massage groups(including massage for 10 min, 20 min, and 30 min group by random number table), 10 rabbits in each group. In addition to the blank group, CSA rabbit model was made by injection of sclerosing agent in other groups. The rabbits of massage for 10 min, 20 min, and 30 min groups received the massage therapy of corresponding duration, one times a day, continuous 10 days. The blood flow of vertebral artery in each group was detected by PeriFlux5000 laser doppler, and the contents of NPY and ET-1 in serum were detected by ELISA before and after treatment.</p><p><b>RESULTS</b>Changes in blood flow of vertebral artery before and after treatment:there was no significant difference between model group and massage for 10 min group;there was significant difference between model group and massage for 20, 30 min groups(<0.01); there was significant difference between massage for 10 min group and massage for 20, 30 min groups(<0.01); there was no significant difference between massage for 20 min group and massage for 30 min group. Changes of NPY content before and after treatment: there was significant difference between model group and massage for 10 min group(<0.05); there was significant difference between model group and massage for 20, 30 min groups(<0.01); there was significant difference between massage for 10 min group and massage for 20, 30 min groups(<0.01); there was no significant difference between massage for 20 min group and massage for 30 min group. Changes of ET-1 content before and after treatment:there was no significant difference between model group and massage for 10 min group;there was significant difference between model group and massage for 20, 30 min groups(<0.01); there was significant difference between massage for 10 min group and massage for 20 min, 30 groups (<0.01); there was no significant difference between massage for 20 min group and massage for 30 min group.</p><p><b>CONCLUSIONS</b>Massage needed 20 min for rabbits with CSA can only significantly improve the blood flow of vertebral artery. However, prolonging the time of massage has no obvious effect. The material basis of this timeliness characteristic of massage is closely related to the change of NPY and ET-1 levels in serum.</p>

Metabolic Profile of Dyskinetic Cerebral Palsy Based on Metabonomics / 中国康复理论与实践

Objective To analyze the metabolic profile of children with dyskinetic cerebral palsy by metabolomics, and its abnormal metabolic pathway. Methods The serum of 10 children with dyskinetic cerebral palsy (patient group) and 7 healthy children (control group) aged 6 to 12 years were collected at clinic from May to August, 2014. The serum samples were tested by the nuclear magnetic resonance spectrometer and the spectroscopies were discriminated by partial least squares-discriminant analysis. According to the human metabolome database, the final metabolites disturbed would be figured out. Results 15 chemical shifts were defined, and 6 of them, including 2.04 ppm, 2.12 ppm, 3.00 ppm, 3.24 ppm, 3.76 ppm, 6.50 ppm, were significantly different between 2 groups (P<0.05). The KEGG Pathway Database showed that the levels of taurine, fumarate, oxaloacete, pyruvate, citrate, aspartate, succinate, malate, cysteine decreased, and the levels of glutamate, 2-oxoglutarate, glutamine, leucine, alanine increased. The abnormal metabolism was found in taurine metabolism, glutamine me-tabolism and energy metabolism pathways. Conclusion Based on metabolomics, the metabolic profile of children with dyskinetic cerebral palsy was discriminated out successfully. The further research can focus on the small molecules found out.

Role of Diffusion Weighted Magnetic Resonance Imaging at 3-T in Staging of Endometrial Cancer and Correlation to Histopathology.

Aim: To investigate the value of diffusion weighted imaging (DWI) at 3-T MR in staging of endometrial cancer and the correlation to histopathology. Study Design: A retrospective study. Place and Duration of Study: CT-MR Division, Qianfoshan Hospital Affiliated to Shandong University. Department of Radiology, Affiliated Hospital of Jining Medical College. From June 2013 to June 2014 Methodology: 30 patients with histologically proved endometrial cancers were analyzed retrospectively. The staging diagnosis of DWI was compared with pathologic results. The ADC values in different histologic types and different differentiated of endometrial cancers were also compared. P<0.05 was considered statistically significant. Results: The staging accuracy of DWI was 83.3%. The ADC value in 30 patients of endometrial cancer was (0.856±0.080) ×10-3 mm2/s. There was no statistically significant difference in different histologic types (t=1.093，P=0.284). In different differentiated endometrial cancers, there was significant difference (F=97.246，P=0.000). Conclusion: DWI has considerable value in staging of endometrial cancer. The ADC values can demonstrate the grade malignancy of tumors initially. So diffusion weighted sequences can be included in routine MR protocols for tumor assessment.

Multicenter Evaluation of the Molecular Line Probe Assay for Multidrug Resistant Mycobacterium Tuberculosis Detection in China / 生物医学与环境科学（英文）

In order to evaluate the performance of a molecular Hain line probe assay (Hain LPA) for rapid detection of rifampicin and isoniazid resistance of Mycobacterium tuberculosis in China, 1612 smear positive patients were consecutively enrolled in this study. Smear positive sputum specimens were collected for Hain LPA and conventional drug susceptibility testing (DST). The sensitivity and specificity of Hain LPA were analyzed by using conventional DST as golden reference. The sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) for rifampicin resistance detection were 88.33%, 97.66%, 81.54%, and 98.62%, respectively. The sensitivity, specificity, PPV and NPV for isoniazid resistance detection were 80.25%, 98.07%, 87.25%, and 96.78%, respectively. These findings suggested that Hain LPA can be an effective method worthy of broader use in China.

Effect of 1,25-dihydroxyvitamin D₃on regulatory T cells in ovariectomized mice / 生物医学与环境科学（英文）

<p><b>OBJECTIVE</b>To investigate the correlation between regulatory T (Treg) cells and postmenopausal osteoporosis and the antiosteoporotic effect of 1,25-dihydroxyvitamin D3 [1,25(OH)₂D₃] in relation to Treg cells.</p><p><b>METHODS</b>Fifty female BALB/c mice were randomly divided into five groups: the basal control (BAS), Sham, ovariectomy (OVX), OVX+diethylstilbestrol (OVX+DES), and OVX+1,25(OH)₂D₃. Tibias were harvested and processed with decalcification for quantitative bone histomorphometry. Femurs were stained by immunohistochemistry to detect Foxp3 protein expression. Spleens were used to detect Treg and Foxp3 gene expression by flow cytometry and quantitative RT-PCR, respectively.</p><p><b>RESULTS</b>In comparison with the Sham group, a significant decrease was found in the OVX group in such indices as trabecular bone volume/total tissue area (BV/TV), trabecular number (Tb.N) and trabecular thickness (Tb.Th). 1,25(OH)₂D₃and DES partly prevented the decrease in BV/TV, Tb.N, Tb.Th in OVX mice. Treg cell number, Foxp3 mRNA expression in spleen and Foxp3 protein expression in femur significantly decreased in the OVX-treated group compared with those in the sham group. 1,25(OH)2D₃and DES significantly increased Treg cell number and Foxp3 expression. Treg cells and Foxp3 gene expression were related to bone histomorphometric parameters.</p><p><b>CONCLUSION</b>The decrease in Treg cell numbers is relevant to the postmenopausal osteoporosis. The antiosteoporosis of 1,25(OH)₂D₃is related to regulatory T cells.</p>

Study on the asexual sporulation of Aspergillus niger under blue light induction and analysis of its subtractive library / 生物工程学报

The effect of blue light (BL) on the morphological development of Aspergillus niger was studied by the scanning electron microscopy (SEM) observation. Comparing with the darkness, BL was able to stimulate development of sporangiophore and conidiosphore, promote grownth of mycelium. Suppression subtractive hybridization (SSH) was conducted with tester cDNA which was from 39 to approximately 40h-old mycelium cultured under darkness and driver cDNA which was from mycelium illuminated for 3 to approximately 4h under BL after dark growth. Some cDNA bands were obtained by suppression PCR (polymerase chain reaction) with the subtractive cDNA. Positive bacterial clones were randomly picked and identified by colony PCR method. Through sequence alignments from GenBank, most of differential cDNA fragments were highly identical with some redox enzymes existing in mitochondria, and the quantitative measurement of these differential mRNA by real time RT-PCR indicated that relative expression of the identified gene fragments under BL induction was higher than that under darkness. Furthermore, the result suggested that some respiratory chain redox enzymes of mitochondria were involved in the photoresponse and consequently influence the metabolism. Among differential cDNA fragments two unkown sequences were found and their complete gene and gene function remained to be investigated.

Analysis of clinicopathologic features and morphogenesis of carcinoid tumorlets in the lung with bronchiectasis / 中华病理学杂志

<p><b>OBJECTIVE</b>To describe the clinicopathologic features and immunophenotypes of carcinoid tumorlets in the lung with bronchiectasis, and to study the morphogenesis of these tiny tumors.</p><p><b>METHODS</b>The histopathologic characteristics of 3 bronchiectasis cases with carcinoid tumorlets, 11 bronchiectasis and 2 normal lungs were studied. Specific markers of the tiny tumors and the number of neuroendocrine cells (NECs) in the airway mucosa were immunohistochemically detected by EnVision method.</p><p><b>RESULTS</b>The tumorlets in the lungs presented as multi-focal nodules and most were displayed only under microscopy. These cells were arranged in clusters and foci of fascicles which were situated in the surrounding bronchial wall and bronchioles adjacent to bronchiectatic lesion, or in the scar tissues. The tiny tumors were consisted of short fusiform cells and small ovoid cells. Their nuclei were circular, oval or long fusiform and the cells were strongly argyrophilic on Grimelius staining. Intensive positive immunostaining for calcitonin, chromogranin A, NSE and gastrin were detected. Weak positive for CK, EMA, S-100 and focal positive for HC, ACTH, 5-HT were also observed. Proliferative NECs in airway mucosa adjacent to the tiny tumors increased significantly in number, compared with those in the airway mucosa of bronchiectasis without tumorlets and normal lungs (P < 0.001, respectively).</p><p><b>CONCLUSIONS</b>The clinicopathologic features and immunophenotypes of carcinoid tumorlets resemble carcinoid tumors. They are the early stage of carcinoid development. Their development may be related to the chronic pulmonary damage resulting in hypoxia and stimulating the proliferation of NECs. These pulmonary carcinoid tumorlets can be used as a model to study the tumorigenesis of carcinoid carcinoma of the lung.</p>