Advances in antitumor research of bifunctional small molecule inhibitors targeting heat shock protein 90 / 药学学报

The heat shock protein 90 (Hsp90) protein family is a cluster of highly conserved molecules that play an important role in maintaining cellular homeostasis. Hsp90 and its co-chaperones regulate a variety of pathways and cellular functions, such as cell growth, cell cycle control and apoptosis. Hsp90 is closely associated with the occurrence and development of tumors and other diseases, making it an attractive target for cancer therapeutics. Inhibition of Hsp90 expression can affect multiple oncogenic pathways simultaneously. Most Hsp90 small molecule inhibitors are in clinical trials due to their low efficacy, toxicity or drug resistance, but they have obvious synergistic anti-tumor effect when used with histone deacetylase (HDAC) inhibitors, tubulin inhibitors or topoisomerase II (Topo II) inhibitors. To address this issue, the design of Hsp90 dual-target inhibitors can improve efficacy and reduce drug resistance, making it an effective tumor treatment strategy. In this paper, the domain and biological function of Hsp90 are briefly introduced, and the design, discovery and structure-activity relationship of Hsp90 dual inhibitors are discussed, in order to provide reference for the discovery of novel Hsp90 dual inhibitors and clinical drug research from the perspective of medicinal chemistry.

Research progress of Parkin protein regulating mitochondrial homeostasis through ubiquitination in cardiovascular diseases / 中国药理学通报

In addition to providing energy for cells, mitochondria also participate in calcium homeostasis, cell information transfer, cell apoptosis, cell growth and differentiation. Therefore, maintaining mitochondrial homeostasis is very crucial for the body to carry out normal life activities. Ubiquitination, a post-translational modification of proteins, is involved in various physiological and pathological processes of cells by regulating mitochondrial homeostasis. However, the mechanism by which ubiquitination regulates mitochondrial homeostasis has not been summarized, especially the effect of Parkin protein on cardiovascular diseases. In this paper, the specific mechanism of mitochondrial homeostasis regulated by ubiquitination of Parkin protein is discussed, and the influence of mitochondrial homeostasis imbalance on cardiovascular diseases is reviewed, with a view to providing potential therapeutic strategies for the clinical treatment of cardiovascular diseases.

Research progress on the application of combining radiotherapy and systemic therapy in breast cancer / 国际肿瘤学杂志

Compared with single therapy, radiotherapy combined with chemotherapy, endocrine therapy, molecular targeted therapy and immunological therapy can not only shorten the treatment cycle, but also improve the local control rate and prolong the survival of patients. However, the safety of combined therapy still needs to be further clarified to comprehensively evaluate the feasibility. Therefore, exploring the efficacy and safety of radiotherapy combined with systematic therapy will provide evidence for clinical benefits.

Characteristics analysis of HBV serological markers of NAT reactive blood donors under different HBsAg status / 中国输血杂志

【Objective】 To investigate the characteristics of HBV serological markers of NAT reactive blood donors under different HBsAg status. 【Methods】 NAT reactive samples, with HBsAg-, HBsAg+ /retest - and HBsAg+ by single reagent were collected from September 2021 to May 2022 in our laboratory. The TMA non-reactive samples were retested by Roche PCR, then HBsAg, anti-HBs, HBeAg, anti-HBe and anti-HBc were detected by ECLI for statistical analysis. 【Results】 A total of 66 samples were collected, among which 55 were HBsAg-/NAT+. The positive rate of anti-HBc, anti-HBs+ anti-HBc, anti-HBe+ anti-HBc was 87.3% (48/55), 43.6% (24/55) and 45.5% (25/55), respectively. The positive rate of anti-HBs was 10.9% (6/55) and the overall negative rate was 1.8% (1/55). In 7 HBsAg+ initially/retest -/NAT+ samples, the positive rate of anti-HBc was 100%(7/7), and the positive rate of anti-HBe+ anti-HBc was 71.4%(5/7). In 4 HBsAg+ /NAT+ samples by single reagent, the positive rate of HBsAg+ anti-HBs+ anti-HBe+ anti-HBc was 50% (2/4), and positive rate of anti-HBe+ anti-HBc was100% (4/4). Samples, not reactive to TMA discriminatory and anti-HBc negative, were also non-reactive to individual PCR retest. There were significant differences in the positive rates of anti-HBe+ anti-HBc between HBsAg-/NAT+ samples and HBsAg+ /NAT+ (single reagent) samples (P<0.05). 【Conclusion】 Most HBsAg-/NAT+ blood donors were occult hepatitis B virus infection.The anti-HBe+ anti-HBc positive were correlated with HBV infection status. Non-reactivity discriminated by TMA plus anti-HBc negative do not exclude HBV DNA non-reactivity.

Effect of breastfeeding on immune function in infants with human cytomegalovirus infection / 中国当代儿科杂志

OBJECTIVES@#To study the effect of breastfeeding on immune function in infants with human cytomegalovirus (HCMV) infection.@*METHODS@#A retrospective analysis was performed on the medical data of 135 infants with HCMV infection who were admitted to Children's Hospital Affiliated to Zhengzhou University from January 2021 to May 2022, and all these infants received breastfeeding. According to the results of breast milk HCMV-DNA testing, the infants were divided into two groups: breast milk HCMV positive (n=78) and breast milk HCMV negative (n=57). According to the median breast milk HCMV-DNA load, the infants in the breast milk HCMV positive group were further divided into two subgroups: high viral load and low viral load (n=39 each). Related indicators were compared between the breast milk positive and negative HCMV groups and between the breast milk high viral load and low viral load subgroups, including the percentages of peripheral blood lymphocyte subsets (CD3+ T cells, CD3+CD4+ T cells, CD3+CD8+ T cells, and CD19+ B cells), CD4+/CD8+ ratio, IgG, IgM, IgA, and urine HCMV-DNA load.@*RESULTS@#There were no significant differences in the percentages of CD3+ T cells, CD3+CD4+ T cells, CD3+CD8+ T cells, and CD19+ B cells, CD4+/CD8+ ratio, IgG, IgM, IgA, and urine HCMV-DNA load between the breast milk HCMV positive and HCMV negative groups, as well as between the breast milk high viral load and low viral load subgroups (P>0.05).@*CONCLUSIONS@#Breastfeeding with HCMV does not affect the immune function of infants with HCMV infection.

Reference values for carotid artery intima-media thickness among community adult dwellers in Shenzhen City / 中华预防医学杂志

Objective: To establish reference values for carotid intima-media thickness (CIMT) of adult dwellers in Shenzhen City. Methods: The study was conducted based on the Shenzhen heart failure epidemiological survey from 2021 to 2022. In this survey, residents aged 18 years and above in Shenzhen were selected by using a multi-stage stratified random sampling method. General information, cardiovascular disease (CVD) related behavior and carotid ultrasound examination and etc. were collected from the participants. People with CVD factors, a history of atherosclerotic cardiovascular disease, carotid plaque or having no carotid ultrasound examination results were excluded. The parameter regression model based on fractional polynomial was used to establish the reference values of CIMT by age and sex. Results: A total of 2 163 healthy individuals were enrolled in the final analysis, including 576 males (26.6%) and 1 587 females (73.4%). The fractional polynomial regression of the CIMT mean and standard deviation was obtained. For men, the regression was meanCIMT=0.324 7+0.006 9×age and SDCIMT=0.076 9+0.001 2×age. For women, the regression was meanCIMT=0.354 9+0.005 4×age and SDCIMT=0.041 6+0.002 0×age. Conclusion: The age and sex reference values for CIMT of adult people in Shenzhen established in this study could provide the latest reference standards for early screening of subclinical CVD.

Effects of circ-SFMBT2 on Proliferation, Migration and Invasion of Acute Myeloid Leukemia Cells by Regulating miR-491-5p/HOXA9 Axis / 中国实验血液学杂志

OBJECTIVE@#To explore the effects and molecular mechanism of circ-SFMBT2 on the proliferation, migration and invasion of acute myeloid leukemia (AML) cells.@*METHODS@#Bone marrow samples from 35 pediatric AML patients and 35 healthy controls in Henan Provincial Children's Hospital from April 2015 to April 2017 and human bone marrow stromal cell lines (HS-5) and AML cell lines (HL-60, THP-1, U-937 and Kasumi-1) were collected. The expressions of circ-SFMBT2, miR-491-5p and homeobox A9 (HOXA9) in bone marrow samples and cells were detected by RT-qPCR and Western blot. The Pearson method was used to analyze the correlation of circ-SFMBT2, miR-491-5p and HOXA9 mRNA expression levels in bone marrow samples of AML patients. HL-60 cells were cultured in vitro and divided into 5 groups: Control, si-NC, si-circ-SFMBT2, si-circ-SFMBT2+anti-NC and si-circ-SFMBT2+anti-miR-491-5p, HL-60 cells were transfected with si-NC, si-circ-SFMBT2, anti-NC, and miR-491-5p inhibitor with Lipofectamine™ 3000. RT-qPCR and Western blot were performed to detect the expression levels of circ-SFMBT2, miR-491-5p and HOXA9 in cells of each group. The proliferation activity of HL-60 cells in each group was detected by CCK-8 assay at 24, 48 and 72 h after transfection, respectively. The apoptosis rate was detected by flow cytometry. The migration and invasion abilities of cells were detected by Transwell assay. The regulatory roles of circ-SFMBT2, miR-491-5p and HOXA9 in AML cells were verified by dual-luciferase reporter gene assay, RNA pull-down and RNA-binding protein immunoprecipitation (RIP) experiments.@*RESULTS@#The expression levels of circ-SFMBT2 and HOXA9 mRNA were increased in bone marrow samples and cell lines (HL-60, THP-1, U-937 and Kasumi-1) of children with AML (P <0.001), while the expression level of miR-491-5p was significantly decreased (P <0.001). Pearson correlation analysis showed that the expression levels of circ-SFMBT2 and miR-491-5p in bone marrow samples of AML children were negatively correlated (r =-0.905), miR-491-5p was also negatively correlated with HOXA9 mRNA (r =-0.930), while the expression levels of HOXA9 mRNA and circ-SFMBT2 was positively correlated (r =0.911). The overall survival rate of AML children with high expression of circ-SFMBT2 was significantly decreased than those with low expression of circ-SFMBT2 (P <0.05). Silencing of circ-SFMBT2 could greatly up-regulate the expression of miR-491-5p, decrease the expression of HOXA9, inhibit the proliferation, migration and invasion of AML cells, and promote cell apoptosis (P <0.05). Down-regulation of miR-491-5p expression greatly attenuated the inhibitory effects of circ-SFMBT2 silencing on cell proliferation, migration and invasion (P <0.05). Dual-luciferase reporter gene assay, RNA pull-down and RIP experiments confirmed that circ-SFMBT2 could target miR-491-5p and negatively regulate the expression of miR-491-5p in AML, and HOXA9 was the target of miR-491-5p.@*CONCLUSION@#Silencing of circ-SFMBT2 may inhibit the proliferation, migration and invasion of AML cells by regulating the miR-491-5p/HOXA9 axis.

Metabolomic Analysis of Urine in Rat Model with Spleen-stomach Damp-heat Syndrome / 中国实验方剂学杂志

ObjectiveTaking the rat model of spleen-stomach damp-heat syndrome（SSDHS） as the research object， this study aimed to investigate the potential biomarkers of SSDHS and the related metabolic pathways based on urine metabolomics， and tried to reveal the essence of SSDHS at the level of endogenous small molecular metabolites. MethodSixteen SD rats were randomly divided into normal and model groups. The normal group was fed normal chow and the model group was fed with 200 g·L-1 honey water daily， and lard and Chinese Baijiu alternately on alternate days for 17 days. The SSDHS model rats were exposed to external dampness-heat environment with temperature at 30-34 ℃， relative humidity of 95% for 2 h at the same time every day from the 10th day for 7 d. Then， the model was evaluated by observing the general conditions of the rats， measuring the contents of motilin（MTL） and gastrin（GT） in plasma by enzyme-linked immunosorbent assay（ELISA）， and examining the histopathology of gastronitestinal tissues. In additon， the urine metabolomics analysis was performed by ultra-high performance liquid chromatography-quadrupole-time-of-flight mass spectrometry（UPLC-Q-TOF-MS）， and the detection conditions was as follows：ACQUITY™ UPLC BEH C18 column（2.1 mm×100 mm， 1.7 μm）， mobile phase of 0.1% formic acid aqueous solution（A）-0.1% formic acid acetonitrile solution（B） for gradient elution （0-3 min， 1%-18%B； 3-8 min， 18%-40%B； 8-10 min， 40%-100%B）， the flow rate of 0.4 mL·min-1， electrospray ionization（ESI） in positive and negative ion modes， scanning range of m/z 50-1 000. The univariate and multivariate statistical analysis were constructed for screening inter-group differential ions， the element composition was calculated according to the precise relative molecular weight， and ion information was matched with databases such as Human Metabolome Database（HMDB） to identify biomarkers. Kyoto Encyclopedia of Genes and Genomes（KEGG） database was used to obtain the biological information of metabolites， and their associated metabolic pathways were analyzed by MetaboAnalyst 5.0. ResultCompared with the normal group， the rectal temperature of the model group increased significantly（P<0.01）， the levels of plasma MTL and GT decreased significantly（P<0.05， P<0.01）， and pathological changes such as bleeding， congestion and inflammatory infiltration in the gastric and colonic tissues. A total of 25 differential metabolites such as L-histidine， citric acid and isocitric acid were found to be the potential biomarker of SSDHS by urine metabolomics， 13 of which were phase Ⅱ metabolites of endogenous substances（glucuronic acid conjugates， sulfuric acid conjugates and acetyl conjugates）， involving the metabolic pathways of histidine metabolism， tricarboxylic acid cycle， glyoxylate and dicarboxylate metabolism. ConclusionSSDHS primarily causes disorders of histidine metabolism， tricarboxylic acid cycle， glyoxylate and dicarboxylate metabolism， as well as the imbalance of the activation/inactivation of endogenous metabolites， which may involve the immune response， material and energy metabolism， inflammatory response and intestinal flora， and may provide a basis for the establishment and application of SSDHS model.

Optimization and Developmental Validation of 38-plex InDel Panel for Ancestry Inference / 法医学杂志

OBJECTIVES@#The previously established 38-plex InDel system was optimized and its performance was validated according to the Scientific Working Group on DNA Analysis Method (SWGDAM) application guidelines. The ancestry inference accuracy of individuals from East Asian, European, African and mixed populations was verified.@*METHODS@#DNA standard sample 9947A was used as the template to establish the optimal amplification conditions by adjusting primer balance, Mg2+ final concentration and optimizing PCR thermal cycle parameters and amplification volume. The allelic dropout, nonspecific amplification and whether the origin of the inferred samples matched the known information were compared to evaluate the performance of this system.@*RESULTS@#The optimal dosage of this system was 0.125-2 ng DNA template. The results of InDel typing were accurate, the amplification equilibrium was good, and the species specificity was good. This system showed certain tolerance to DNA samples including the inhibitor such as hemoglobin (≤80 μmol/L), indigo (≤40 mmol/L), calcium ion (≤1.0 mmol/L), and humic acid (≤90 ng/μL). The system enabled the direct amplification of DNA from saliva and blood on filter paper, and the results of ethnic inference were accurate. The system successfully detected the mixed DNA sample from two individuals. The test results of the system for common biological materials in practical cases were accurate.@*CONCLUSIONS@#The results of the 38-plex InDel system are accurate and reliable, and the performance of the system meets the requirement of the SWGDAM guidelines. This system can accurately differentiate the ancestry origins of individuals from African, European, East Asian, and Eurasian populations and can be implemented in forensic practice.

Detection of drug resistance genes of mycobacterium tuberculosis by rolling circle amplification technique with multicolor fluorescent probes / 中华预防医学杂志

The aim of this study was to construct a simple, rapid and ultra-sensitive optical biosensing technique based on rolling circle amplification (RCA), and to apply it to multiple detection of drug-resistant genes of mycobacterium tuberculosis. The common mutation sites of isoniazid, rifampicin and streptomycin resistance genes are katG315 (AGC➝ACC), rpoB531 (CAC➝TAC) and rpsL43 (AAG➝AGG). For these three gene sites, from February 2020 to May 2021, in the Department of Laboratory Medicine of the First Affiliated Hospital of Army Military Medical University, the padlock probe (PLP), primers and capture probes were designed. And a solid-phase RCA constant temperature amplification reaction system based on magnetic beads was constructed and the experimental parameters were optimized. The RCA products were accurately captured by the multicolor fluorescent probes (Cy3/Cy5/ROX), and the single-tube multiple detection of three mutation genes was realized. The sensitivity, specificity and linear range of this method were further verified. The results showed that the response range of katG315 in the same reaction system ranged from 1.0 pmol/L to 0.1 nmol/L. The response range of rpoB531 and rpsL43 ranged from 1.0 pmol/L to 50.0 pmol/L and 1.0 pmol/L to 20.0 pmol/L, and the method had good specificity and sensitivity, and could accurately identify single base mutations in mixed targets, with the minimum detection limit as low as 1.0 pmol/L. The recoveries of simulated serum samples were 95.0%-105.2%. In conclusion, the constant temperature amplification multiple detection method constructed in this study can quickly realize the single-tube multiple detection of three drug resistance mutation sites. This technology is low-cost, simple and rapid, and does not rely on large equipment, providing a new analysis method for pathogen drug resistance gene detection.

Effect of Aqueous Extract of Trametes robiniophila on Proliferation of Human Prostate Cancer VCaP Cells / 中国实验方剂学杂志

ObjectiveTo investigate effect of aqueous extract of Trametes robiniophila （TRM，Huaier） on autophagy of human prostate cancer VCaP cells and Lamin B1 expression， so as to uncover its role in the proliferation of VCaP cells. MethodThe inhibitory effect of 0， 2， 4， 6， 8， 10 g·L-1 TRM aqueous extract on the proliferation of human prostate cancer VCaP cells at different time points were determined by cell counting kit-8 （CCK-8） assay. Acridine orange staining was conducted for analyzing the effect of TRM aqueous extract on the formation of autolysosomes in VCaP cells. After medication， the expression of microtubule-associated protein Ⅰ light chain 3 （LC3）， autophagy-related protein 3 （Atg3）， autophagy-related protein 5 （Atg5）， and autophagy-related protein 7 （Atg7） in VCaP cells were detected by Western blot. The effect of TRM aqueous extract alone and its combination with autophagy inhibitor bafilomycin A1 on the proliferation of VCaP cells were assayed by CCK-8 assay. RNA interference technology was used to explore the role of Lamin B1 in anti-proliferation of VCaP cells by TRM. ResultCompared with the blank group， TRM aqueous extract inhibited the proliferation of human prostate cancer VCaP cells in a time- and concentration-dependent manner （P<0.01）. Acridine orange staining showed that TRM aqueous extract promoted the formation of autolysosomes in VCaP cells. As revealed by Western blotting， TRM aqueous extract up-regulated the expression levels of LC3-Ⅱ， Atg3， Atg5， and Atg7 in contrast to those in the blank group （P<0.05）. All these indicated that TRM aqueous extract induced the autophagy of VCaP cells. In addition， autophagy inhibition impaired the sensitivity of VCaP cells to TRM aqueous extract （P<0.05）. The comparison with the blank group showed that TRM aqueous extract inhibited Lamin B1 protein expression in VCaP cells （P<0.01）， which in turns weakened the sensitivity of VCaP cells to TRM aqueous extract. ConclusionTRM aqueous extract inhibited the proliferation of human prostate cancer VCaP cells possibly by inducing autography and down-regulating Lamin B1 expression. This study has provided a theoretical basis for the clinical application of TRM.

Correlation between eating behaviors with body composition among medical students / 中国学校卫生

Objective@#To investigate the correlation between body composition and eating habits among medical students, and to provide evidence for health promotion.@*Methods@#In December 2021, stratified cluster random sampling method was used to conduct a questionnaire survey and body composition assessment among 445 students in grade one to grade four in Jining Medical University.@*Results@#There were 152 girls (53.3%) and 45 boys (28.1%) with low skeletal muscle mass. Totally 167 students ( 37.5% ) had lower muscle mass, including 115 females (40.4%) and 49 males (30.6%). High body fat percentage was found in 259 (58.2%) students, including 179 females (62.8%) and 80 males (50.0%). There were 192 students (43.1%) with abnormal waist to hip ratio, with 139 females (48.8%) and 53 males (33.1%). In addition, emotional eating score of female students was significantly higher than that of male students(6.85±2.24, 6.11±2.69, t =2.96, P <0.05). Cognitive restricted eating was positively correlated with skeletal muscle mass and musde mass( r=0.13, 0.13, P <0.05). Emotional eating was positively correlated with body fat percentage, body fat and waist hip ratio( r =0.20, 0.20, 0.16, P <0.05). Unrestricted eating was positively correlated with body fat percentage, body fat and waist hip ratio( r =0.15, 0.18, 0.15, P <0.05). Multiple linear regression analysis showed that gender, family residence, physical activity and cognitive eating were associated with skeletal muscle mass and muscle mass of medical students( P <0.05).@*Conclusion@#With low skeletal muscle mass, low muscle mass, body fat percentage and waist and hip high ratio, reasonable eating habits combined with resistance exercise should be adopted to improve their physical health.

Emerging pathogenic role of group 3 innate lymphoid cells in inflammatory diseases / 生理学报

Group 3 innate lymphoid cells (ILC3) as a family member of innate lymphoid cells (ILCs), have been defined as novel innate immune cells in the past decade. ILC3 include a variety of heterogenous subsets with different phenotypes and functions, which are mainly distributed in barrier organs such as the intestine, lung and skin. They play an important role in immune regulation, tissue repair and lymphoid tissue formation. However, in various inflammatory diseases, ILC3 become dysregulated and participate in the pathogenesis through secreting a series of cytokines such as interleukin (IL)-17, IL-22, interferon-γ (IFN-γ) and granulocyte-macrophage colony-stimulating factor (GM-CSF) to modulate other immune cells and induce the formation of ectopic lymphoid structures. Therefore, it is of great significance to explore the phenotype and function of ILC3 in order to advance the understanding of inflammatory diseases and find new therapeutic targets. In this article, the phenotypic characteristics, biological functions and research progress of ILC3 in inflammatory diseases were reviewed.

Identification of key genes and pathways associated with esophageal adenocarcinoma development based on GEO database and bioinformatics / 西安交通大学学报(医学版)

【Objective】 To investigate the potential genes and pathways associated with esophageal adenocarcinoma through microarray expression profiling data analysis and bioinformatics approaches. 【Methods】 The mRNA expression microarray data related to esophageal adenocarcinoma development were screened out with GEO database, and the biological processes, signaling pathways and network of these genes were statistically analyzed using "R" software. 【Results】 The GSE26886 was obtained from GEO database. A total of 1383 differentially expressed genes were associated with carcinogenesis of esophageal adenocarcinoma, including 607 up-regulated and 776 down-regulated genes. These genes were involved in metabolism, stimulate responses, cell adhesion, cell regeneration and immune biological processes. Eight significantly enriched pathways were identified by pathway analysis. 【Conclusion】 The bioinformatic method can analyze the gene chip data effectively. Multiple genes and signaling pathways are involved in the carcinogenesis of esophageal adenocarcinoma, which provides a new idea or approach for exploring biomarkers of early screening and therapeutic targets.

Analysis of HBV serological markers of donor blood samples implicated in TMA triplex + but discriminatory test-samples / 中国输血杂志

【Objective】 To explore the status of HBV infection and low viral load of HBV DNA in blood donor samples implicated in TMA triplex reactive but discriminatory test non-reactive samples. 【Methods】 A total of 51 996 samples were detected by Procleix Panther nucleic acid detection(NAT) system from January 2020 to March 2021, and 86 of them were TMA triplex reactive but discriminatory test non-reactive. HBV serological markers (HBsAg, anti-HBs, HBeAg, anti-HBe, anti-HBc) were detected by electrochemiluminescence. Single-donation(ID) NAT was conducted in some TMA triplex + /discriminatory test-samples using Roche NAT. 【Results】 Out of 86 TMA triplex + /discriminatory test-samples, anti-HBc were positive in 89.53% (77/86), anti-HBe positive in 27.90% (24/86) and anti-HBs positive in 65.12% (56/86). 15 donors carried anti-HBs, anti-HBe and anti-HBc, 34 both anti-HBs and anti-HBc, 1 both anti-HBs/anti-HBe, 8 both anti-HBe/anti-HBc, 6 solo anti-HBs, and 20 solo anti-HBc. The positive rate of HBV serological markers was 97.67% (84/86). HBV DNA in 5 out of the 10 samples was qualitatively detected by Roche ID NAT, and one of them presented HBV DNA < 20 IU/mL. 【Conclusion】 Most TMA triplex + /discriminatory test-samples were occult hepatitis B infection.

Bioinformatics analysis on differential expression genes of neutrophilic asthma and drug screening / 中国药理学通报

Aim To explore the differential expression genes (DEGs) and potential therapeutic drugs of neutrophilic asthma (NA) based on bioinformatics analysis and molecular docking. Methods The gene expression profiles of NA were obtained from GEO database, and the differential expression genes were screened. The protein-protein interactions (PPI) of DEGs were obtained from STRING database, and the hub genes were screened by Cytoscape according to the degree of DEGs. The GO and KEGG pathway analysis were performed by DAVID database. Finally, molecular docking technology was used to screen the potential therapeutic drugs for the treatment of NA. Results A total of 147 DEGs were obtained from NA patients compared with healthy people in GEO database. Ten hub genes were screened from PPI network, including CXCL8, FPR2, CXCL1, TNFRSF1B, CXCR1, etc. Go enrichment analysis showed that DEGs were mostly associated with inflammation, immune response and chemotaxis, etc. KEGG pathway analysis indicated that the DEGs were mainly involved in cytokine-cytokine receptor interaction and complement and coagulation signaling pathways. Molecular docking showed that paeoniflorigenone and triptolide had good binding activity with C8B and PLAU. Conclusion Complement and coagulation cascades may become a new therapeutic target of NA. The two screened compounds paeoniflorigenone and triptolide may be potential therapeutic drugs for the treatment of NA.

Application and prospect of organoid culture in cancer / 中国药理学通报

At present, the traditional models for cancer research include the 2D cell model, human tumor xenograft model and animal model. With the deepening of research, the traditional tumor model is unable to meet the needs of researchers. Organoid model is derived from the surgical specimens of tumor patients, which can completely preserve the histological and genomic characteristics of tumor. It can be used in the research of tumor pathogenesis, drug screening, personalized treatment of patients, etc. Compared with traditional model, it has the advantages of short modeling time, economic benefits and closer-ness to the characteristics of the original tumor. This paper mainly focuses on the research status of organoid technology in tumor, the application of organoid model in treatment, and the advantages of organoid model compared with traditional model, so as to provide reference for the follow-up research.

Dosimetric study of hippocampal protective whole brain radiotherapy based on Varian accelerator / 中国辐射卫生

Objective The purpose of this study is to provide a reference for the selection of clinical radiotherapy plan by comparing the difference of dosimetry between coplanar dynamic intensity modulation dIMRT and coplanar VMAT plan in hippocampal protective whole brain radiotherapy (WBRT). Methods 10 patients were selected whose hippocampal were protected by WBRT, dIMRT and VMAT plans were designed for each patient, the differences of target dose, organ-endangering dose and machine hop count were compared between the two groups. Results The two technical plans PTV V30 Gy, D98% and D2% all meet the standard of RTOG 0933, which is better than the dIMRT group for the PTV HI VMAT group (P = 0.004). The hippocampal dose of dIMRT group was better than that of VMAT group, but it did not meet the standard of RGOT 0933. The average Dmax of hippocampus in dIMRT group and VMAT group was 18.44 Gy and 19.30 Gy, respectively (P = 0.004). The average value of hippocampal Dmin was 10.03 Gy and 10.77 Gy, respectively (P = 0.013), and the mean value of hippocampal Dmean was 14.20 Gy and 15.12 Gy, respectively (P = 0.002). The doses of lens, eyeball and optic nerve all met the standard of RTOG0933, and the dose of dIMRT group was significantly better than that of VMAT group (P = 0.000). The treatment time in VMAT group was significantly lower than that in dIMRT group. The treatment time in VMAT group was significantly lower than that in dIMRT group. Conclusion Varian dIMRT has more advantages in controlling hippocampal dose and protecting lens than VMAT, but PTV HI and treatment efficiency are higher in VMAT group.

Anti-contactin-associated protein-1 antibody associated chronic inflammatory demyelinating polyradiculoneuropathy: a case report / 中华神经科杂志

Chronic inflammatory demyelinating polyneuropathy (CIDP) with positive anti-contactin-associated protein-1 (Caspr1) antibody is a rare autoimmune antibody mediated peripheral neuropathy. A 62-year-old male patient was reported in this article, whose clinical manifestations were subacute onset, abnormal distal limb motor sensation, and increased cerebrospinal fluid protein level. The patient had a good response to plasma exchange. Electromyography of lower limbs showed that motor involvement was dominant, motor conduction velocity slowed down, compound motor active potential (CMAP) and sensory nerve active potential amplitude decreased, and F wave was not elicited; electromyography of upper limbs without symptoms showed that CMAP amplitude of median nerve decreased, and conduction velocity was normal. There are few reports of anti-Caspr1 positive CIDP in the world. The article summarized the characteristics of the patient and reviewed the relevant literature, in order to improve clinicians′ understanding and diagnosis and treatment ability of the disease.

Comparison of MRI and CT for target volume delineation and dose coverage for partial breast irradiation in patients with breast cancer / 中华放射肿瘤学杂志

Objective:To compare magnetic resonance imaging (MRI)-based and computed tomography (CT)-based target volume delineation and dose coverage in partial breast irradiation (PBI) for patients with breast cancer, aiming to explore the application value of MRI localization in PBI after breast-conserving surgery.Methods:Twenty-nine patients with early breast cancer underwent simulating CT and MRI scans in a supine position. The cavity visualization score (CVS) of tumor bed (TB) was evaluated. The TB, clinical target volume (CTV), planning target volume (PTV) were delineated on CT and MRI images, and then statistically compared. Conformity indices (CI) between CT- and MRI-defined target volumes were calculated. PBI treatment plan of 40 Gy in 10 fractions was designed based on PTV-CT, and the dose coverage for PTV-MRI was evaluated.Results:The CVS on CT and MRI images was 2.97±1.40 vs. 3.10±1.40( P=0.408). The volumes of TB, CTV, PTV on MRI were significantly larger than those on CT, (24.48±16.60) cm 3vs. (38.00±19.77) cm 3, (126.76±56.81) cm 3vs. (168.42±70.54) cm 3, (216.63±81.99) cm 3vs. (279.24±101.55) cm 3, respectively, whereas the increasing percentage of CTV and PTV were significantly smaller than those of TB. The CI between CT-based and MRI-based TB, CTV, PTV were 0.43±0.13, 0.66±0.11, 0.70±0.09( P<0.001), respectively. The median percentage of PTV-MRI receiving 40 Gy dose was 81.9%(62.3% to 92.4%), significantly lower than 95.6%(95.0%~97.5%) of PTV-CT. Conclusions:The CVS between CT and MRI is not significantly different, but the MRI-based TB, CTV, PTV are significantly larger than CT-based values. The PTV-MRI is of underdose if PBI treatment plan is designed for PTV-CT. As a supplement of CT scan, MRI can enhance the accuracy of TB delineation after breast-onserving surgery.