Genome-wide identification of GSK gene family in Senna tora L. and expression analyses / 药学学报

Glycogen synthase kinase 3/SHAGGY-like kinase (GSK3) proteins play important roles in regulating plant growth, development, and stress response. In order to reveal the characteristics of GSK family members in the medicinal plant Senna tora L., in this study, we conducted the identification and expression analyses of GSKs in S. tora based on its whole genome data, combined with bioinformatics and gene expression research methods. The results showed that a total of nine S. tora GSK genes were identified, all of which contained the GSK characteristic kinase domains. All members were distributed on six chromosomes, the encoding amino acid length ranged from 465 to 943 aa, the protein molecular weight was from 33.57 to 88.83 kDa, and the average isoelectric point was 8.2. The StoSKs were divided into four evolutionary branches, and the StoSKs in the same evolutionary branch shared the same exon/intron structure and conserved motifs. The expansion of the StoSKs gene family was mainly due to segment duplication events, and there were 17, 11, 8 and 7 pairs of collinear genes with Glycine max, Medicago truncatula, Arabidopsis thaliana and Oryza sativa, respectively. The promoter regions of StoSKs mostly contained responses elements related to stress stimulation, growth and development, and hormone induction. Transcriptome data analysis showed that StoSKs were expressed in different tissues, with the highest expression level in roots. Quantitative real-time PCR (qRT-PCR) analysis indicated that StoSKs in different evolutionary branches displayed a synergistic expression pattern response to light, and most of StoSKs could rapidly respond to NaCl stress with significantly up-regulated expression. All the results provide a basis for further analysis of the biological functions of the GSKs gene family in S. tora.

Predictive value of serum lactate dehydrogenase on prognosis of patients with paraquat poisoning / 中华劳动卫生职业病杂志

Objective: To investigate the predictive value of serum lactate dehydrogenase (LDH) in the prognosis of patients with paraquat (PQ) poisoning, and to provide evidence for early prognosis assessment. Methods: In February 2022, 50 patients with PQ poisoning who completed serum LDH detection admitted to the Department of Emergency Medicine, the First Affiliated Hospital of Wenzhou Medical University from January 2012 to December 2021 were selected as the observation group, and 50 healthy physical examination personnel were randomly selected as the control group. Patients with PQ poisoning were divided into survival group and death group according to the prognosis, and the differences of blood routine routine, liver and kidney function and other indicators in the first admission between the two groups were compared. Multivariate logisitic regression model was established, ROC curve was drawn, and the influencing factors of prognosis of patients with PQ poisoning were analyzed. Results: Compared with the control group, the white blood cell count (WBC), total bilirubin (TBil), alanine aminotransferase (ALT), aspartate aminotransferase (AST), LDH, glucose (GLU) and creatinine (Cr) in observation group were significantly increased, while albumin (ALB) and total cholesterol (TC) were significantly decreased (P<0.05). Univariate analysis showed that WBC, elevated LDH (>247 U/L), TBil, ALT, AST and Cr were significantly different between PQ poisoning survival group and death group (P<0.05). Multivariate logisitic regression analysis showed that elevated serum LDH was an independent risk factor for the prognosis of PQ poisoning patients (OR=9.95, 95%CI: 1.34-73.82, P=0.025). The area under the ROC curve of LDH was 0.811 (95%CI: 0.692-0.930). When the cut-off value was 340 U/L, the sensitivity was 0.889 and the specificity was 0.719. Log-rank test showed that there was a statistically significant difference in survival rate between the normal LDH group and the elevated LDH group (P=0.001) . Conclusion: Serum LDH has a good predictive value in evaluating the prognosis of patients with PQ poisoning. Elevated LDH is a risk factor for poor prognosis of patients with PQ poisoning.

Immunomodulatory Biomaterials and Emerging Analytical Techniques for Probing the Immune Micro-Environment

After implantation of a biomaterial, both the host immune system and properties of the material determine the local immune response. Through triggering or modulating the local immune response, materials can be designed towards a desired direction of promoting tissue repair or regeneration. High-throughput sequencing technologies such as single-cell RNA sequencing (scRNA-seq) emerging as a powerful tool for dissecting the immune micro-environment around biomaterials, have not been fully utilized in the field of soft tissue regeneration. In this review, we first discussed the procedures of foreign body reaction in brief. Then, we summarized the influences that physical and chemical modulation of biomaterials have on cell behaviors in the micro-environment. Finally, we discussed the application of scRNA-seq in probing the scaffold immune micro-environment and provided some reference to designing immunomodulatory biomaterials. The foreign body response consists of a series of biological reactions. Immunomodulatory materials regulate immune cell activation and polarization, mediate divergent local immune micro-environments and possess different tissue engineering functions. The manipulation of physical and chemical properties of scaffolds can modulate local immune responses, resulting in different outcomes of fibrosis or tissue regeneration. With the advancement of technology, emerging techniques such as scRNA-seq provide an unprecedented understanding of immune cell heterogeneity and plasticity in a scaffold-induced immune micro-environment at high resolution. The in-depth understanding of the interaction between scaffolds and the host immune system helps to provide clues for the design of biomaterials to optimize regeneration and promote a pro-regenerative local immune micro-environment.

Periodontitis as a promoting factor of T2D: current evidence and mechanisms / 国际口腔科学杂志·英文版

Periodontitis is an infectious disease caused by an imbalance between the local microbiota and host immune response. Epidemiologically, periodontitis is closely related to the occurrence, development, and poor prognosis of T2D and is recognized as a potential risk factor for T2D. In recent years, increasing attention has been given to the role of the virulence factors produced by disorders of the subgingival microbiota in the pathological mechanism of T2D, including islet β-cell dysfunction and insulin resistance (IR). However, the related mechanisms have not been well summarized. This review highlights periodontitis-derived virulence factors, reviews how these stimuli directly or indirectly regulate islet β-cell dysfunction. The mechanisms by which IR is induced in insulin-targeting tissues (the liver, visceral adipose tissue, and skeletal muscle) are explained, clarifying the influence of periodontitis on the occurrence and development of T2D. In addition, the positive effects of periodontal therapy on T2D are overviewed. Finally, the limitations and prospects of the current research are discussed. In summary, periodontitis is worthy of attention as a promoting factor of T2D. Understanding on the effect of disseminated periodontitis-derived virulence factors on the T2D-related tissues and cells may provide new treatment options for reducing the risk of T2D associated with periodontitis.

Analysis of Chemical Composition in Essential Oil of Zanthoxyli Pericarpium from Different Producing Areas and Investigation of Antifungal Effect of Zanthoxyli Pericarpium Essential Oil Solid Preparation / 中国实验方剂学杂志

Objective:To extract essential oil of Zanthoxyli Pericarpium， to prepare Zanthoxyli Pericarpium essential oil solid preparation and investigate its anti-fungal effect， in order to provide safe， green and efficient fungicide for the storage of Chinese herbal medicine and food. Method:The essential oil of Zanthoxyli Pericarpium was extracted by steam distillation method， gas chromatography-mass spectrometry （GC-MS） was adopted to analyze the chemical compositions and their relative contents in essential oil of Zanthoxyli Pericarpium from different producing areas， Agilent HP-5 capillary column was used for separation at programmed temperature （the initial temperature was 60 ℃， kept for 2 min， then increased to 280 ℃ by 10 ℃·min^-1， kept for 5 min）， the scanning range was <italic>m</italic>/<italic>z</italic> 35-590. Zanthoxyli Pericarpium essential oil solid preparation was prepared by nanomolecular sieve adsorption method， and its inhibitory effect on <italic>Aspergillus flavus</italic> and its conidia was investigated. Ultra-high performance liquid chromatography-fluorescence detector （UPLC-FLD） was used to analyze the inhibitory effect of Zanthoxyli Pericarpium essential oil solid preparation on aflatoxin under the conditions of excitation wavelength of 360 nm and emission wavelength of 440 nm. Result:The average extraction rate of essential oil in Zanthoxyli Pericarpium from four producing areas was 5.2%. （+）-Limonene， linalool and linalyl acetate were the main components of Zanthoxyli Pericarpium<italic> </italic>essential oil<italic> </italic>from different producing areas. When the volume fraction of essential oil in the solid preparation was 0.1%， the inhibition rate of the solid preparation on the conidia of <italic>A</italic>. <italic>flavus</italic> was （16.41±8.89）%. When the volume fraction of essential oil in the solid preparation was 0.2%， the inhibition rate for the growth of <italic>A</italic>. <italic>flavus</italic> was （8.11±2.70）%. When the volume fraction of essential oil in the solid preparation was 0.5%， the inhibition rate for the growth of <italic>A</italic>. <italic>flavus </italic>was （21.62±5.41）%， the inhibition rate for <italic>A</italic>. <italic>flavus</italic> conidia was （45.43±5.67）%， and the inhibition effect for the aflatoxin could reach （90.47±12.77）%. Conclusion:There are some differences in the chemical composition of essential oil of Zanthoxyli Pericarpium from different producing areas. Zanthoxyli Pericarpium<italic> </italic>essential oil has a certain inhibitory effect on the formation of <italic>A. flavus</italic> conidia and the production of aflatoxin B₁. It shows that Zanthoxyli Pericarpium essential oil can be developed into bacteriostatic preparation and used in the storage of Chinese medicinal materials and food.

Analysis of Mechanism of Chloroform Extract of Gegen Qinliantang on Alleviating Enterotoxicity Induced by Irinotecan / 中国实验方剂学杂志

Objective:Considering the efficacy of Gegen Qinliantang （GQT） in releasing exterior and clearing interior to alleviate dampness-heat dysentery， we analyzed the mechanism of the chloroform extract of GQT in alleviating enterotoxicity caused by irinotecan to provide an experimental basis for the development of GQT. Method:Kunming mice （<italic>n</italic>=60） were randomly divided into a blank group， a model group， a loperamide group （positive drug of loperamide hydrochloride capsule， 0.4 mg·kg^-1）， and high- （2.3 g·kg^-1） and low-dose （1.16 g·kg^-1） GQT chloroform extract groups. The mouse model of delayed diarrhea was established by intraperitoneal injection of irinotecan hydrochloride （CPT-11， 55 mg·kg^-1） for four consecutive days， meanwhile， the mice in the blank group only received the same volume of normal saline. Corresponding drugs were administered by gavage on the fifth day， respectively， while the ones in the blank group and model group were given distilled water for five consecutive days. The general condition of mice in each group was observed， and diarrhea indexes of mice were recorded. Pathological changes in colon tissues of mice were observed by hematoxylin-eosin （HE） staining. The tumor necrosis factor （TNF）-<italic>α</italic>， interleukin （IL）-1<italic>β</italic>， cyclooxygenase （COX）-2， intercellular adhesion molecule （ICAM）-1， glutathione peroxidase （GSH-Px）， superoxide dismutase （SOD）， malondialdehyde （MDA） and nitric oxide （NO） levels in colon tissues were detected with the assay kits. Furthermore， the expression levels of Kelch sample epoxy chloropropane associated protein 1 （Keap1）， nuclear factor E₂ related factor 2 （Nrf2）， tight junction protein-1 （ZO-1）， heme oxygenase-1 （HO-1） and tight junction protein （Occludin） were detected by Western blot. Result:Compared with the blank group， the model group showed declined body weight and reduced contents of GSH-Px and SOD （<italic>P</italic><0.01）， whereas increased diarrhea indexes and TNF-<italic>α</italic>， IL-1<italic>β</italic>， COX-2， ICAM-1， MDA and NO levels （<italic>P</italic><0.01）. Abundant inflammatory cells and colonic mucosa with defects， swelling， bleeding， and inflammatory exudation were revealed by HE staining in the mice of the model group. The expression levels of Keap1， Nrf2， ZO-1， HO-1 and Occludin in colon tissues significantly declined （<italic>P</italic><0.01）. Compared with the model group， the loperamide group and the high- and low-dose GQT chloroform extract groups exhibited improved weight loss， reduced diarrhea indexes， diminished TNF-<italic>α</italic>，<italic> </italic>IL-1<italic>β</italic>， COX-2， ICAM-1， MDA and NO， and elevated GSH-Px and SOD. HE staining indicated that the cells were compactly arranged with clear nuclei in the high- and low-dose GQT chloroform extract groups， and the expression levels of Keap1， Nrf2， HO-1， Occludin， and ZO-1 were up-regulated. Conclusion:GQT chloroform extract may alleviate CPT-11-induced delayed diarrhea by regulating inflammation and oxidative stress for enhancing the intestinal barrier function. These findings are expected to provide a reference for exploring the toxicity-attenuating effect of Chinese medicinals on chemotherapy drugs and for developing famous classical formulas.

Value of three-dimensional DSA simulation for the side selection of pterional approach to clip anterior communicating artery aneurysms / 中国脑血管病杂志

Objective To evaluate the safety and efficiency of the treatment strategy based on three-dimensional digital subtraction angioplasty (3 D-DSA) for the side selection of pterional approach to clip anterior communicating artery aneurysm. Methods All 75 continuous patients with single anterior communicating artery aneurysm(Hunt-Hess 0-III grade) treated by microsurgical clipping via the pterional approach were analyzed retrospectively. The side selection of approach was based on 3D-DSA. All patients' gender, age, Hunt-Hess grade, aneurysm size, the side of approach, complications, the length of postoperative stay, the ratio of complete occlusion, and the Glasgow outcome scale (GOS) score at discharge were collected. The ratio of complete occlusion and clinical outcome were analyzed according to the group of left or right approach and different Al dominant approach. Results (1) Fifty-six patients (74. 7%) were left Al dominants, with 30 of those treated via the left-side approach and 26 of those treated via the right-side approach. Nineteen patients (25.3%) were right Al dominants, with 15 of those treated via the right-side approach and 4 of those treated via the left-side approach. (2) Surgical exposure of all aneurysms was satisfactory during operation, which was consistent with the 3D-DSA image simulation before the operation. The median length of postoperative stay was 9(8, 11) days. Six patients(8. 0%) suffered symptomatic cerebral infarction, and 1 patient (1.3%) had an intracranial infection. Sixty-five cases performed DSA or CT antigraphy after the operation. Sixty-two aneurysms (95.4%) were completely clipped and 3 aneurysms (4.6%) existed residual segments in the neck of the aneurysm. Sixty-nine patients (92.0%) reached 5 grade of GOS, 3 patients (4.0%) reached 4 grade of GOS, 3 patients (4.0%) reached 3 grade of GOS, and no patient was below 3 grade of GOS at discharge. (3) The surgical-related complications, clipping results, hospital-stay time after operation, and GOS at discharge were insignificantly different between left and right side approach, also insignificantly different between the dominant Al side and contralateral side approach. Conclusion The treatment strategy, based on preoperative 3D-DSA imaging simulation for the side selection of pterional approach to clip anterior communicating artery aneurysms, was safe and effective.

Discovery of a highly selective VEGFR2 kinase inhibitor CHMFL-VEGFR2-002 as a novel anti-angiogenesis agent

Angiogenesis is an essential process in tumor growth, invasion and metastasis. VEGF receptor 2 (VEGFR2) inhibitors targeting tumor angiogenic pathway have been widely used in the clinical cancer treatment. However, most of currently used VEGFR2 kinase inhibitors are multi-target inhibitors which might result in target-associated side effects and therefore limited clinical toleration. Highly selective VEGFR inhibitors are still highly demanded from both basic research and clinical application point of view. Here we report the discovery and characterization of a novel VEGFR2 inhibitor (CHMFL-VEGFR2-002), which exhibited high selectivity among structurally closed kinases including PDGFRs, FGFRs, CSF1R, etc. CHMFL-VEGFR2-002 displayed potent inhibitory activity against VEGFR2 kinase in the biochemical assay (IC = 66 nmol/L) and VEGFR2 autophosphorylation in cells (ECs ∼100 nmol/L) as well as potent anti-proliferation effect against VEGFR2 transformed BaF3 cells (GI = 150 nmol/L). In addition, CHMFL-VEGFR2-002 also displayed good anti-angiogenesis efficacy and exhibited good PK (pharmacokinetics) profile with bioavailability over 49% and anti-angiogenesis efficacy in both zebrafish and mouse models without apparent toxicity. These results suggest that CHMFL-VEGFR2-002 might be a useful research tool for dissecting new functions of VEGFR2 kinase as well as a potential anti-angiogenetic agent for the cancer therapy.

Long Non-Coding RNA HULC Enhances Tumor Growth in Orthotopic Xenograft Model of Glioblastoma / 中山大学学报(医学科学版)

@#【Objective】To investigate the mechanism of action of long non-coding RNA highly up-regulated in liver cancer（LncRNA HULC）on the growth of glioblastoma U87 cells in vitro and in vivo.【Methods】The cultured glioblastoma U87 cells were divided into four groups：overexpression group（HULC-over）and its vector control group（VEC），silent expression group（HULC- siRNA）and its negative control group（NC）.Quantitative real- time polymerase chain reaction PCR（qRT-PCR）was used to verify the expression levels of HULC. CCK8 proliferation assay and colony formation assay were adopted to monitor the proliferation of glioblastoma U87 cells. Flow cytometry was utilized to detect the apoptosis of glioblastoma U87 cells. By injecting U87 cells，we divided the orthotopic xenograft mouse model into HULC- over group（n=10），VEC group（n=10），HULC-siRNA group（n=10）and NC group（n=10）accordingly. The survival of the mice in each group was observed. The expression of Ki67 was analyzed by immunohistochemistry. 【Results】 The expression level of HULC was significantly higher in HULC-over group than that in VEC group and significantly lower in HULC-siR NA group than that in NC group（P < 0.01）. The cell proliferation ability was significantly increased in HULC-over group compared with that in VEC group and significantly decreased in HULC- siRNA group compared with that in NC group（P < 0.01 on days2，3and4）. The colony formation rates in VEC group，HULC-over group，NC group and HULC-siRNA group were，respectively，（34.47 ± 1.56）% ，（95.4 ± 2.74）% ，（23.83 ± 0.92）% and （10.23 ± 0.61）% ，which revealed that overexpression of HULC elevated the colony formation rate and silencing expression of HULC reduced the colony formation rate（P < 0.01）. The early apoptosis rates in VEC group，HULC- over group，NC group and HULC- siRNA group were，respectively，（3.55±0.56）% ，（0.09±0.01）% ，（2.89±0.67）% ，and（7.13±0.14）% ，which showed that overexpression of HULC elevated the early apoptosis rate and silencing expression of HULC reduced the early apoptosis rate （P <0.01）. The survival curve of nude mouse indicated shorter survival time in HULC-over group than that in VEC group and longer survival time in HULC-siRNA group than that in NC group（P < 0.05）. Ki67 protein expression was up-regulated in the HULC-over group compared with that in VEC group and down-regulated in the HULC-siRNA group compared with that in NC group（P < 0.05）.【Conclusion】LncRNA HULC can enhance the growth of glioblastoma U87 cells in vitro and in vivo.

Surgical treatment of infracardiac total anomalous pulmonary venous connection: A retrospective cohort study / 中国胸心血管外科临床杂志

@#Objective    To compare the outcomes of sutureless technique and conventional technique in the surgical repair for infracardiac total anomalous pulmonary venous connection (TAPVC). Methods    The clinical data of 46 consecutive patients with infracardiac TAPVC undergoing surgical repair in our hospital between June 2014 and April 2019 were retrospectively analyzed. Patients with combined congenital cardiac anomalies such as single ventricle and tetralogy of Fallot were excluded. Patients were divided into a conventional technique group and a sutureless technique group according to the surgical techniques. There were 35 patients in the conventional technique group, including 28 males (80.0%) and 7 females (20.0%) with a median age of 21 (8, 42) d and a median weight of 3.6 (3.0, 4.0) kg. There were 11 patients in the sutureless technique group, including 8 males (72.7%) and 3 females (27.3%) with a median age of 14 (6, 22) d and a median weight of 3.5 (2.9, 3.6) kg. The curative effect of the two groups was compared. Results    There were 5 deaths (10.9%) in the conventional technique group, including 4 in-hospital deaths (8.7%) and 1 late death (2.2%). Overall mortality of the conventional technique group (14.3%, 5/35) was higher than that of the sutureless technique group (0.0%, 0/11), although the difference was not statistically significant (P=0.317). Cox regression analysis showed that sex (P=0.042), age at repair (P=0.028), cardiopulmonary bypass time (P=0.007), aortic cross-clamping time (P=0.018) and duration of ventilation (P=0.042) were risk factors for postoperative mortality. The median follow-up was 18.00 (5.00, 37.75) months. Postoperative pulmonary venous obstruction occurred in 22 patients of the conventional technique group, which was significantly more than that of the sutureless technique group (P=0.000). Conclusion    For infracardiac TAPVC, sutureless technique can reduce the incidence of postoperative pulmonary venous obstruction compared with conventional technique.

The functional role of temporal structure in human perception: behavioral evidence and neural correlates / 生理学报

To extract the temporal structure of sensory inputs is of great significance to our adaptive functioning in the dynamic environment. Here we characterize three types of temporal structure information, and review behavioral and neural evidence bearing on the encoding and utilization of such information in visual and auditory perception. The evidence together supports a functional view that the brain not only tracks but also makes use of temporal structure from diverse sources for a broad range of cognitive processes, such as perception, attention, and unconscious information processing. These functions are implemented by brain mechanisms including neural entrainment, predictive coding, as well as more specific mechanisms that vary with the type of temporal regularity and sensory modality. This framework enriches our understanding of how the human brain promotes dynamic information processing by exploiting regularities in ubiquitous temporal structures.

Isolation and Identification of Chemical Constituents from Goodyera schlechtendaliana / 中国实验方剂学杂志

Objective:To isolate and purify the chemical constituents from Goodyera schlechtendaliana, and lay a foundation for further research on the effective materials of the plant. Method:The dried grass of G. schlechtendaliana(10 kg)was heated by 95% EtOH for reflux extraction for 4 times at 85℃. The extract liquids were combined, decompressed and concentrated to obtain the crude extract. The crude extract was then suspended in distilled water and extracted with petroleum ether,EtOAc and n-BuOH in turn to obtain corresponding fractions. Silica gel,Sephadex LH-20,ODS and semi-preparation high performance liquid chromatography (HPLC) were used for the separation and purification of EtOAc and n-BuOH fractions. The structures of compounds obtained were identified by 1H-NMR,13C-NMR,MS,physicochemical properties and reference literature. Result:Ten compounds were isolated and identified as 2,5-dihydroxy-4-methoxy-9,10-dihydroxyphenanthrene (1),1,3,5-trimethoxybenzene (2),protocatechuic acid (3),p-hydroxybenzaldehyde (4),p-hydroxybenzoic acid (5),quercetin (6),vanillin(7),daucosterol (8),adenine (9) and adenosine (10). Conclusion:Compounds 1-10 were obtained from the genus of Goodyera for the first time.

Long-term efficacy of dendritic cell vaccines combined with cytokine-induced killer cells in the treatment of metastatic renal cell carcinoma / 中国肿瘤生物治疗杂志

@# Objective: To evaluate the long-term clinical efficacy and follow-up of dendritic cell (DC) vaccines in combination with cytokine-induced killer cell (CIK) treatment in metastatic renal cell carcinoma. Methods: From January 2011 to December 2013, 29 patients with metastatic renal cell carcinoma (pathologically confirmed as renal clear cell carcinoma) were treated by DC vaccines-CIK at the Department of Hematopoietic Stem Cell Transplantation, the Fifth Medical Center of Chinese PLA General Hospital. The 29 patients included 24 male and 5 female, with a median age of 57(32-81) years old. Mature DC vaccine was obtained by gene transfection technology and CIK cells were obtained by i n v i t r o culture; and DC vaccine-CIK was infused back to patients through lymphatic drainage area and vein by each course. Twelve patients received first line treatment, 6 patients received second line treatment after the disease progression by targeted drug therapy or cytokine therapy, and 11 patients received third-linetreatment or above. The long-term clinical efficacy and overall survival rate were evaluated. Results: The median follow-up time was 5 (1-7) years. Treatment cycle was over 2 (2-23) cycles. One case (3.4%) achieved complete remission, 9 cases (31%) achieved partial responses, 13 cases (44.8%) demonstrated stable disease over 3 months and 6 patients (20.7%) developed progressive disease. The objective response rate was 34.4%,and the disease control rate was 79.2%. Stable disease for more than one year realized in 19 cases (65.5%). The 1-, 3- and 5-year survival rates were 93.1% (27/29), 65.5% (20/29) and 51.7% (15 / 29), respectively. Neither the median progression-free survival (PFS) nor the median survival time was achieved. No adverse reactions above grade 3 were observed during treatment. Conclusion: DC vaccines-CIK therapy for the treatment of metastatic renal cell carcinoma is affirmative; it achieved good disease control and long-term survival with controllable safety, and prolonged the survival time for advanced renal cell carcinoma patients.

CRS after CAR-T therapy: mechanism of occurrence and clinical treatment / 中国肿瘤生物治疗杂志

@#Chimeric antigen receptor T-cell (CAR-T) targeting CD19 has made significant progress in the treatment of B cell malignancies. FDA has approved two CD19 CAR-T therapeutic products. With the development in the clinical and mechanism research of immunotherapy (CAR-T, bispecific T-cell engager [BiTE]), dual affinity re-targeting [DART], and genetically modified T cell receptorT cell [TCR-T]), its potential risks and side effects have been more widely recognized, especially cytokine release syndrome (CRS). CRS is currently the most common complication after CAR-T treatment and can be life-threatening in severe cases. Moreover, the pathophysiological process of CRS is complex, involving a variety of immune cells and non-immune cells, and can affect whole body organs. Elucidating the mechanisms of CRS development is of great significance to improve the safety of CAR-T therapy. In recent years, researchers have conducted study in animal models to illustrate the mechanisms of CRS more deeply. This review discusses the development, pathophysiological mechanisms, animal models, clinical features, and graded treatments of CRS, aiming to provide an in-depth understanding of the mechanism of CRS and improve the safety of CAR-T therapy.

Effects of Silencing Expression of Long Non-Coding RNA HULC on Proliferation and Apoptosis of Human Glioblastoma Cell SHG44 / 中山大学学报(医学科学版)

@#【Objective】 To explore the effects of long- chain non- coding RNA highly up- reglated in liver cancer（LncRNA HULC）silencing expression on proliferation and apoptosis of human glioblastoma cell line SHG44.【Methods】 Quantitative Real- time Polymerase Chain Reaction （qRT- PCR） was used to verify the expression level of HULC in HULC silent expression group （HULC- siRNA）and negative control group （NC group）. CCK8 proliferation assay and plate colony formation assay were used to detect the proliferation of glioblastoma cells. Cell cycle and apoptosis assays were used to detect the cell cycle distribution and apoptosis of glioblastoma cells. 【Results】 qRT- PCR confirmed that HULC- siRNA group had significantly lower expression of HULC than NC group （P=0.003）. CCK8 proliferation experiment showed that the proliferation rate of HULC-siRNA group was significantly lower than that of NC group on the second，third and fourth days of experiment（Day 2，P=0.003；Day 3，P=0.005；Day 4，P=0.009）. Plate colony formation assay showed the cloning rates in the NC and HULC-siRNA groups were（34.11 ± 1.24）% and（14.44 ± 0.87）%，and it showed that the cell clone formation rate was clearly decreased after silenced expression of HULC （P<0.001）. The cell cycle assay showed that the numbers of cells in NC group and HULC-siRNA group were G1 phase（36.89 ± 4.09，51.74± 0.68）and S phase（46.95 ± 2.49，36.89 ± 2.13），and it showed that the cell cycle was blocked in G1/S phase after silencing HULC expression （G1 phase，P=0.023，S phase，P=0.038）. Apoptosis experiment showed that the early apoptotic rates of NC group and HULC-siRNA group were（2.57 ± 0.22）% and（7.063 ± 0.71）%，and it showed that the early apoptotic rate of the cells was significantly increased after silencing HULC expression （P=0.004）. 【Conclusion】 Silencing of LncRNA HULC can inhibit the proliferation of glioblastoma cells and promote their apoptosis.

Characteristics of inguinal hernia in adolescents in China and the problems deserving attention in diagnosis and treatment / 中国实用外科杂志

There is no authoritative definition of adolescents in the world which is generally believed that the age ranges from 10 to 19. At present, there are few surveys on the prevalence of inguinal hernia among adolescents at home and abroad. Adolescents are in the process of vigorous growth and development, and the diagnosis and treatment of inguinal hernia is special. There is still much controversy in the treatment of inguinal hernia. In view of the special group of inguinal hernia patients, adolescents should formulate corresponding treatment plan according to their specific characteristics. Detailed preoperative evaluation should be done to find out if there were any special cases(such as hydrocele of testis and cryptorchidism). According to preoperative evaluation, reasonable surgical methods and repairing materials should be selected, carefully operate during surgery, and protect spermatic cord vessels and vas deferens to the maximum extent to avoid adverse complications. Tissue repair or patch reinforcement should be considered according to the degree of posterior inguinal canal defect.

Effects of orchinol on invasion, migration and Wnt3a/β-catenin signaling pathway of human gastric cancer SGC-7901 cells / 中国中药杂志

The purpose of this study was to investigate the inhibitory effect of the main 9,10-dihydrophenanthrene orchinol isolated from Spiranthes sinensis Radix et Herba on the invasion and migration of human gastric cancer SGC-7901 cells and its preliminary molecular mechanism. SGC-7901 cells were cultured in vitro, after the cells were treated with different final concentrations(5, 10, 20, 40, 80 μmol·L⁻¹) of orchinol for 24, 48 or 72 hours, the effect of orchinol on cell viability was measured by MTT assay. Wound healing and Transwell assays were performed to determine the effects of different final concentrations(5, 10, 20, 40 μmol·L⁻¹) of orchinol for 48 hour on invasion and migration abilities of SGC-7901 cells, respectively. The protein expression levels of β-catenin, Wnt-3α, DvL2, cyclinD1 and GSK-3β were detected by Western blot. The results showed that 5-80 μmol·L⁻¹ orchinol inhibited the viability of SGC-7901 cells in a dose-dependent and time-dependent manner, and the IC₅₈ values of 24, 48 and 72 hours were 77.79, 42.96 and 7.85 μmol·L⁻¹, respectively. Compared with the control group, the ability of invasion and migration of SGC-7901 cells was significantly inhibited after treated with 5, 10 and 20 μmol·L⁻¹ orchinol for 48 hours (<0.05, <0.01), and the dose-effect relationship was observed. The results of Western blot showed that orchinol could significantly down-regulate the protein expression levels of β-catenin, Wnt3a, DvL2 and cyclinD1, and up-regulate the protein expression level of GSK-3β(<0.05, <0.01, <0.001). The above results suggest that orchinol can obviously inhibit the invasion and migration of SGC-7901 cells, which may be related to its inhibition of Wnt3a/β-catenin signaling pathway and the proteins expression of downstream genes.

Preparation of multifunctional nanoparticles targeting tongue cancer and in vitro study / 华西口腔医学杂志

<p><b>OBJECTIVE</b>This study aims to prepare docetaxel (DOC)-loaded multifunctional nanoparticles containing indocyanine green (ICG) and perfluorohexane (PFH) as targeted drug delivery system, which is supplemented with stromal cellderived factor-1 (SDF-1), and characterize their properties.</p><p><b>METHODS</b>Multifunctional nanoparticles were prepared by using the double emulsion method. SDF-1 was covalently conjugated to the surface of the nanoparticles through thioether bonding. Their particle size, distribution, and surface potential were determined with the Malvern measuring instrument. The conjugation of SDF-1 was evaluated by confocal laser scanning microscope. Encapsulation efficiency (ELC), drug loading capacity (DLC), and release regularity of the nanoparticles were determined by high-performance liquid chromatography (HPLC). In vitro photothermal property was recorded by a thermal imager. The in vitro imaging capacity was observed by a photoacoustic instrument and an ultrasonic diagnostic apparatus. Targeting capability was assessed by flow cytometry. The cell activity on SCC-15 cells was checked by CCK-8 method.</p><p><b>RESULTS</b>The targeted multifunctional nanoparticles showed regularly sphericity. The diameter was (502.88±17.92) nm. The zeta potential was (-11.5±3.15) mV. ELC was 54.12%±1.74%. DLC was 1.08 mg·mL-1. In vitro drug release was initially fast and subsequently slow. The photothermal characteristics were related to the concentration; the higher the concentration, the higher the temperature. Nanoparticles could detect significant photoacoustic and ultrasound signals. The in vitro targeting rate was 89.99%. No significant differences of cell viability in the SINPs groups were observed at each concentration (P>0.05). The inhibition effect of DOC-SINPs was stronger than that of SINPs whether or not in the presence of laser irradiation among the groups of 150 and 200 μg·mL-1 (P<
0.05).</p><p><b>CONCLUSIONS</b>Multifunctional nanoparticles for diagnosis and treatment were successfully prepared and displayed dualmode ultrasound/photoacoustic imaging and antitumor effects of chemotherapy and photothermal therapy.</p>

Simultaneous Determination of Twelve Kinds of Residual Solvents in A New Drug CBT108 By Headspace Gas Chromatography / 分析化学

A simple and sensitive method for simultaneous determination of 12 kinds of residual solvents in a new drug CBT108 was established and validated by headspace gas chromatographic technology. The rationality,accuracy and feasibility of the analytical method were verified. Under the optimized conditions, simultaneous separation and determination of 12 kinds of residual solvents, including methanol, ethanol, ether, acetone, acetonitrile, dichloromethane, n-hexane, ethyl acetate, tetrahydrofuran, heptane, toluene and carbon tetrachloride was carried out by using a DB624 capillary column(30 m×0.53 mm×3.0 μm) for separation, a flame ionization detector for detection and internal standard method for quantitation. Good linearity was obtained for 12 solvents with the correlation coefficients(R2) of more than 0.997. The limits of quantitation and detection were defined at S/N=3 and S/N=10,respectively. LOQ and LOD for 12 solvents were given as 0.024 μg/mL and 0.0072 μg/mL for methanol,0.1 μg/mL and 0.012 μg/mL for ethanol, 0.01 μg/mL and 0.005 μg/mL for ether, 0.1 μg/mL and 0.008 μg/mL for acetone, 1.025 μg/mL and 0.0615 μg/mL for acetonitrile, 0. 09 μg/mL and 0. 06 μg/mL for dichloromethane, 0. 09 μg/mL and 0.06 μg/mL for n-hexane, 0. 25 μg/mL and 0. 008 μg/mL for ethyl acetate, 0. 108 μg/mL and 0.014 μg/mL for tetrahydrofuran,0.16 μg/mL and 0.0004 μg/mL for carbon tetrachloride,0.0075 μg/mL and 0.005 μg/mL for heptane, and 0.0445 μg/mL and 0.0014 μg/mL for toluene. The adding standards recoveries for 12 residual solvents at three spiked levels were in the range of 90.96%-108.67%,with relative standard deviations of 0.1%-5.7%. This simple,high accuracy and good repeatability method is feasible for rapidly determination of 12 residual solvents in drug candidate CBT108. Meanwhile, this simple method provides a consulted value for detection of residual solvents in other medicines.

Endemic features and space-time clustering of schistosomiasis in Xinjian District,Nanchang City from 2009 to 2014 / 中国血吸虫病防治杂志

Objective To understand the endemic situation and distribution features of schistosomiasis in Xinjian District,Nanchang City,Jiangxi Province from 2009 to 2014,so as to provide a reference for the prevention and control of schistosomia-sis in the future.Methods The endemic data of schistosomiasis in Xinjian District were collected by taking the village as a unit from 2009 to 2014.An endemic database was established,and the SaTScan software was applied to analyze the spatiotemporal aggregation areas of Schistosoma japonicum infection in crowd,Oncomelania hupensis snails and cattle.Results The S.japoni-cum infection rate of crowd was decreased from 0.10％in 2009 to 0.000 68％in 2014.The infection rate of O.hupensis snails was greatly fluctuated from 2009 to 2014,the highest was 1.04％in 2012,but it fell to 0 in 2014.The highest infection rate of cattle was 1.98％in 2012,and it fell to 0 in 2014.The spatial temporal clustering detection showed that three areas of crowd infection were mainly concentrated in 20 villages of Changyi Township,Lianyu Township and Songhu Town;two areas of snail infection were mainly concentrated in five villages of Changyi Township and Nanji Township;one area of cattle infection was mainly con-centrated in three villages of Changyi Township.Conclusions The endemic situation of schistosomiasis presents a declining trend in Xinjian District from 2009 to 2014 as a whole.However,the potential risks of the rebound of the disease still exist,and the six clustering areas of infection are still the key areas for the prevention and control of schistosomiasis in the future.