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.

Regulatory Mechanism of Mangiferin Combined with Bortezomib on Malignant Biological Behavior of Burkitt Lymphoma and Its Effect on Expression of CXC Chemokine Receptors / 中国实验血液学杂志

OBJECTIVE@#To analyze the effects of mangiferin combined with bortezomib on the proliferation, invasion, apoptosis and autophagy of human Burkitt lymphoma Raji cells, as well as the expression of CXC chemokine receptors (CXCRs) family, and explore the molecular mechanism between them to provide scientific basis for basic research and clinical work of Burkitt lymphoma.@*METHODS@#Raji cells were intervened with different concentrations of mangiferin and bortezomib alone or in combination, then cell proliferation was detected by CCK-8 assay, cell invasion ability was detected by Transwell chamber method, cell apoptosis was detected by Annexin V/PI double-staining flow cytometry, apoptosis, autophagy and Akt/mTOR pathway protein expression were detected by Western blot, and the expression changes of CXCR family was detected by real-time quantitative PCR (RT-qPCR).@*RESULTS@#Different concentrations of mangiferin intervened Raji cells for different time could inhibit cell viability in a concentration- and time-dependent manner (r =-0.682, r =-0.836). When Raji cells were intervened by combination of mangiferin and bortezomib, compared with single drug group, the proliferation and invasion abilities were significantly decreased, while the apoptosis level was significantly increased (P <0.01). Mangiferin combined with bortezomib could significantly up-regulate the expression of pro-apoptotic protein Bax and down-regulate the expression of anti-apoptotic protein Bcl-2 after intervention in Raji cells. Caspase-3 was also hydrolyzed and activated, and then induced the apoptosis of Raji cells. Mangiferin combined with bortezomib could up-regulate the expression of LC3Ⅱ protein in Raji cells, and the ratio of LC3Ⅱ/LC3Ⅰ in cells was significantly up-regulated compared with single drug or control group (P <0.01). Mangiferin combined with bortezomib could significantly inhibit the phosphorylation levels of Akt and mTOR, inhibit the proliferation and invasion of Raji cells by inhibiting Akt/mTOR pathway, and induce cell autophagy and apoptosis. Mangiferin and bortezomib could down-regulate the expressions of CXCR4 and CXCR7 mRNA after single-agent intervention in Raji cells, and the down-regulations of CXCR4 and CXCR7 mRNA expression were more significant when the two drugs were combined (P <0.01). Mangiferin alone or combined with bortezomib had no significant effect on CXCR5 mRNA expression in Raji cells (P >0.05), while the combination of the two drugs could down-regulate the expression of CXCR3 (P <0.05).@*CONCLUSION@#Mangiferin combined with bortezomib can synergistically inhibit the proliferation and invasion of Raji cells, and induce autophagy and apoptosis. The mechanism may be related to the inhibition of Akt/mTOR signaling pathway, down-regulation of anti-apoptotic protein Bcl-2 and up-regulation of pro-apoptotic protein Bax, and the inhibition of the expression of CXCR family.

Research Advances on Strategies to Promote Homing and Engraftment of Hematopoietic Stem Cells--Review / 中国实验血液学杂志

The homing and engraftment of hematopoietic stem cells (HSC) into bone marrow is the first critical step for successful clinical hematopoietic stem cell transplantation (HSCT). SDF-1 / CXCR4 is considered to be a very promising target to promote HSC homing. In recent years, with the in-depth research on the HSC homing, a variety of new strategies for promoting HSC homing and engraftment have been explored, such as nuclear hormone receptor, histone deacetylase inhibitor, prostaglandin and metabolic regulation, so as to increase the success rate of HSCT and improve the survival of patients. In this review, the recent research advances in the mechanism of HSC homing and strategies to promote HSC homing and engraftment were summarized and discussed.

Qishen Yiqi Dripping Pills for Cardiovascular Diseases: Effects and Mechanisms / 中国结合医学杂志

Qishen Yiqi Dripping Pills (QSYQ) is a compound of Chinese medicine, which has been used to treat coronary heart disease and cardiac dysfunction. Its natural components include astragaloside IV, flavonoids, danshensu, protocatechualdehyde, salvianolic acid B, salvianolic acid A, ginsenosides Rg1, ginsenosides Rb1, and essential oils, etc. It exerts effects of nourishing qi and promoting blood circulation to relieve pain. In this review, the bioactive components of QSYQ and its effects for treating cardiovascular diseases and possible mechanism were summarized, providing references for further study and clinical application of QSYQ.

Status of fungal sepsis among preterm infants in 25 neonatal intensive care units of tertiary hospitals in China / 中华儿科杂志

Objective: To analyze the prevalence and the risk factors of fungal sepsis in 25 neonatal intensive care units (NICU) among preterm infants in China, and to provide a basis for preventive strategies of fungal sepsis. Methods: This was a second-analysis of the data from the "reduction of infection in neonatal intensive care units using the evidence-based practice for improving quality" study. The current status of fungal sepsis of the 24 731 preterm infants with the gestational age of <34+0 weeks, who were admitted to 25 participating NICU within 7 days of birth between May 2015 and April 2018 were retrospectively analyzed. These preterm infants were divided into the fungal sepsis group and the without fungal sepsis group according to whether they developed fungal sepsis to analyze the incidences and the microbiology of fungal sepsis. Chi-square test was used to compare the incidences of fungal sepsis in preterm infants with different gestational ages and birth weights and in different NICU. Multivariate Logistic regression analysis was used to study the outcomes of preterm infants with fungal sepsis, which were further compared with those of preterm infants without fungal sepsis. The 144 preterm infants in the fungal sepsis group were matched with 288 preterm infants in the non-fungal sepsis group by propensity score-matched method. Univariate and multivariate Logistic regression analysis were used to analyze the risk factors of fungal sepsis. Results: In all, 166 (0.7%) of the 24 731 preterm infants developed fungal sepsis, with the gestational age of (29.7±2.0) weeks and the birth weight of (1 300±293) g. The incidence of fungal sepsis increased with decreasing gestational age and birth weight (both P<0.001). The preterm infants with gestational age of <32 weeks accounted for 87.3% (145/166). The incidence of fungal sepsis was 1.0% (117/11 438) in very preterm infants and 2.0% (28/1 401) in extremely preterm infants, and was 1.3% (103/8 060) in very low birth weight infants and 1.7% (21/1 211) in extremely low birth weight infants, respectively. There was no fungal sepsis in 3 NICU, and the incidences in the other 22 NICU ranged from 0.7% (10/1 397) to 2.9% (21/724), with significant statistical difference (P<0.001). The pathogens were mainly Candida (150/166, 90.4%), including 59 cases of Candida albicans and 91 cases of non-Candida albicans, of which Candida parapsilosis was the most common (41 cases). Fungal sepsis was independently associated with increased risk of moderate to severe bronchopulmonary dysplasia (BPD) (adjusted OR 1.52, 95%CI 1.04-2.22, P=0.030) and severe retinopathy of prematurity (ROP) (adjusted OR 2.55, 95%CI 1.12-5.80, P=0.025). Previous broad spectrum antibiotics exposure (adjusted OR=2.50, 95%CI 1.50-4.17, P<0.001), prolonged use of central line (adjusted OR=1.05, 95%CI 1.03-1.08, P<0.001) and previous total parenteral nutrition (TPN) duration (adjusted OR=1.04, 95%CI 1.02-1.06, P<0.001) were all independently associated with increasing risk of fungal sepsis. Conclusions: Candida albicans and Candida parapsilosis are the main pathogens of fungal sepsis among preterm infants in Chinese NICU. Preterm infants with fungal sepsis are at increased risk of moderate to severe BPD and severe ROP. Previous broad spectrum antibiotics exposure, prolonged use of central line and prolonged duration of TPN will increase the risk of fungal sepsis. Ongoing initiatives are needed to reduce fungal sepsis based on these risk factors.

Progress in research of risk prediction of non-syndromic oral clefts using genetic information / 中华流行病学杂志

Non-syndromic oral cleft (NSOC), a common birth defect, remains to be a critical public health problem in China. In the context of adjustment of childbearing policy for two times in China and the increase of pregnancy at older childbearing age, NSOC risk prediction will provide evidence for high-risk population identification and prenatal counseling. Genome-wide association study and second generation sequencing have identified multiple loci associated with NSOC, facilitating the development of genetic risk prediction of NSOC. Despite the marked progress, risk prediction models of NSOC still faces multiple challenges. This paper summarizes the recent progress in research of NSOC risk prediction models based on the results of extensive literature retrieval to provide some insights for the model development regarding research design, variable selection, model-build strategy and evaluation methods.

Combination immunotherapy of glioblastoma with dendritic cell cancer vaccines,anti-PD-1 and poly I:C / 药物分析学报

Glioblastoma(GBM)is a lethal cancer with limited therapeutic options.Dendritic cell(DC)-based cancer vaccines provide a promising approach for GBM treatment.Clinical studies suggest that other immu-notherapeutic agents may be combined with DC vaccines to further enhance antitumor activity.Here,we report a GBM case with combination immunotherapy consisting of DC vaccines,anti-programmed death-1(anti-PD-1)and poly I:C as well as the chemotherapeutic agent cyclophosphamide that was integrated with standard chemoradiation therapy,and the patient remained disease-free for 69 months.The patient received DC vaccines loaded with multiple forms of tumor antigens,including mRNA-tumor associated antigens(TAA),mRNA-neoantigens,and hypochlorous acid(HOCl)-oxidized tumor lysates.Furthermore,mRNA-TAAAs were modified with a novel TriVac technology that fuses TAAs with a destabilization domain and inserts TAAs into full-length lysosomal associated membrane protein-1 to enhance major histo-compatibility complex(MHC)class Ⅰ and Ⅱ antigen presentation.The treatment consisted of 42 DC cancer vaccine infusions,26 anti-PD-1 antibody nivolumab administrations and 126 poly I:C injections for DC infusions.The patient also received 28 doses of cyclophosphamide for depletion of regulatory T cells.No immunotherapy-related adverse events were observed during the treatment.Robust antitumor CD4+and CD8+T-cell responses were detected.The patient remains free of disease progression.This is the first case report on the combination of the above three agents to treat glioblastoma patients.Our results suggest that integrated combination immunotherapy is safe and feasible for long-term treatment in this patient.A large-scale trial to validate these findings is warranted.

Method establishment of components identification and content determination of index components in Gantaishu capsules / 中国药房

OBJECTIVE To establish methods to identify the chemical components of Gantaishu capsule， and determine the contents of 6 index components including glycyrrhizic acid. METHODS The chemical components of Gantaishu capsule were determined by HPLC-TOF/MS； the contents of 6 index components including glycyrrhizic acid were determined by UPLC-MS/MS. RESULTS A total of 41 chemical components were identified in Gantaishu capsules. The linear ranges of glycyrrhizic acid， mangiferin， luteolin， costunolide， oleanolic acid and berberine were 200-10 000 ng/mL（r were all greater than 0.999）. The limits of quantification were 200， 20， 10， 1， 10， 0.5 ng/mL， and the limits of detection were 100， 10， 5， 0.5， 5， 0.25 ng/mL， respectively； RSDs of precision， stability （24 h） and reproducibility tests were all less than 5.0% （n＝6 or n＝3）； the recoveries were 99.05%-101.08% （RSD were all less than 2.0%， n＝6）. The contents of them were 2.42-2.66， 0.85-1.16， 0.35-0.46， 6.18- 6.46， 0.99-1.29， 5.22-5.56 mg/g. CONCLUSIONS The established methods for identification and content determination are rapid and simple， and can be used for the identification of chemical components and the content determination of index components in Gantaishu capsule.

Diagnosis status and genetic characteristics analysis of Fanconi anemia in China / 中华儿科杂志

Objective: To analyze the clinical and molecular diagnostic status of Fanconi anemia (FA) in China. Methods: The General situation, clinical manifestations and chromosome breakage test and genetic test results of 107 pediatric FA cases registered in the Chinese Blood and Marrow Transplantation Registry Group (CBMTRG) and the Chinese Children Blood and Marrow Transplantation Registry Group (CCBMTRG) from August 2009 to January 2022 were analyzed retrospectively. Children with FANCA gene variants were divided into mild and severe groups based on the type of variant, and Wilcoxon-test was used to compare the phenotypic differences between groups. Results: Of the 176 registered FA patients, 69 (39.2%) cases were excluded due to lack of definitive genetic diagnosis results, and the remaining 107 children from 15 hospitals were included in the study, including 70 males and 37 females. The age at transplantation treatment were 6 (4, 9) years. The enrolled children were involved in 10 pathogenic genes, including 89 cases of FANCA gene, 7 cases of FANCG gene, 3 cases of FANCB gene, 2 cases of FANCE gene and 1 case each of FANCC, FANCD1, FANCD2, FANCF, FANCJ, and FANCN gene. Compound heterozygous or homozygous of loss-of-function variants account for 69.2% (72/104). Loss-of-function variants account for 79.2% (141/178) in FANCA gene variants, and 20.8% (37/178) were large exon deletions. Fifty-five children (51.4%) had chromosome breakage test records, with a positive rate of 81.8% (45/55). There were 172 congenital malformations in 80 children.Café-au-Lait spots (16.3%, 28/172), thumb deformities (16.3%,28/172), polydactyly (13.9%, 24/172), and short stature (12.2%, 21/172) were the most common congenital malformations in Chinese children with FA. No significant difference was found in the number of congenital malformations between children with severe (50 cases) and mild FANCA variants (26 cases) (Z=-1.33, P=0.185). Conclusions: FANCA gene is the main pathogenic gene in children with FA, where the detection of its exon deletion should be strengthened clinically. There were no phenotypic differences among children with different types of FANCA variants. Chromosome break test is helpful to determine the pathogenicity of variants, but its accuracy needs to be improved.

Efficacy of neoadjuvant therapy on HER2-positive breast cancer: a clinicopathological analysis / 中华病理学杂志

Objective: To investigate the efficacy of neoadjuvant therapy (NAT) on HER2-positive breast cancer and to analyze their clinicopathological features. Methods: A total of 480 cases of HER2-positive breast cancer who received neoadjuvant therapy (NAT), diagnosed at the Department of Pathology of Fudan University Shanghai Cancer Center from 2015 to 2020, were retrospectively identified. Clinicopathological parameters such as age, tumor size, molecular subtype, type of targeted therapy, Ki-67 proliferation index, ER and HER2 immunohistochemical expression, and HER2 amplification status were analyzed to correlate with the efficacy of NAT. Results: Among 480 patients with HER2-positive breast cancer, 209 achieved pathology complete response (pCR) after NAT, with a pCR rate of 43.5%. Of all the cases,457 patients received chemotherapy plus trastuzumab and 23 patients received chemotherapy with trastuzumab and pertuzumab. A total of 198 cases (43.3%) achieved pCR in patients with chemotherapy plus trastuzumab, and 11 cases (47.8%) achieved pCR in patients with chemotherapy plus trastuzumab and pertuzumab. The pCR rate in the latter group was higher, but there was no statistical significance. The results showed that the pCR rate of IHC-HER2 3+patients (49%) was significantly higher than that of IHC-HER2 2+patients (26.1%, P<0.001). The higher the mean HER2 copy number in the FISH assay, the higher the pCR rate was achieved. The expression level of ER was inversely correlated with the efficacy of NAT, and the pCR rate in the ER-positive group (28.2%) was significantly lower than that in the ER-negative group (55.8%, P<0.001). The pCR rate (29.1%) of patients with luminal B type was lower than that of HER2 overexpression type (55.8%, P<0.001). In addition, higher Ki-67 proliferation index was associated with higher pCR rate (P<0.001). The pCR rate was the highest in the tumor ≤2 cm group (57.7%), while the pCR rate in the tumor >5 cm group was the lowest (31.1%). The difference between the groups was significant (P=0.005). Conclusions: HER2 copy numbers, HER2 immunohistochemical expression level, molecular subtype, ER expression level and Ki-67 proliferation index are significantly associated with pCR after NAT. In addition, fluorescence in situ hybridization results, HER2/CEP17 ratio and tumor size could also significantly affect the efficacy of NAT.

Characteristics of new corneal biomechanical parameters in different degrees of myopia / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To study the characteristics of new corneal biomechanical parameters in different degrees of myopia and analyze the correlation of the new parameter stress-strain index(SSI).METHODS: A cross-sectional study was conducted on 366 adult patients(718 eyes)with different degrees of myopia who received treatment at the First Affiliated Hospital of Dali University from October 2021 to November 2021, aged 18-50 years, and the spherical equivalent(SE)was -0.50～-16.75D. The axial length(AL)of the eye was measured by IOL master, and the new corneal biomechanical parameters, central corneal thickness(CCT)and intraocular pressure(IOP)were measured by corneal visualization Scheimpflug technology(Corvis ST). The subjects were categorized into low myopia, moderate myopia and high myopia groups according to SE. The data were analyzed by ANOVA and Pearson correlation.RESULTS: The ratio of the thinnest corneal thickness to horizontal thickness change rate(ARTh)and SSI were statistically significant(P&#x0026;#x003C;0.001), while the remaining parameters were not statistically significant(P&#x0026;#x003E;0.05). SSI was positively correlated with age(r=0.102, P=0.006), SE(r=0.361, P&#x0026;#x003C;0.001), IOP(r=0.175, P&#x0026;#x003C;0.001), CCT(r=0.098, P=0.009), SPA1(r=0.182, P&#x0026;#x003C;0.001), negatively correlated with AL(r=-0.331, P&#x0026;#x003C;0.001), IR(r=-0.545, P&#x0026;#x003C;0.001)and had no correlation with other corneal biomechanical parameters(P&#x0026;#x003E;0.05).CONCLUSION: With the increase of myopia degree and the elongation of the axial length, the SSI value becomes smaller and the corneal hardness decreases. SSI may be a helpful corneal biomechanical indicator for future research on myopia.

Clinical features of 23 neonates infected with Omicron variant of severe acute respiratory syndrome coronavirus 2 / 中国当代儿科杂志

OBJECTIVES@#To summarize the clinical features of neonates infected with Omicron variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).@*METHODS@#The medical data of 23 neonates with Omicron variant of SARS-CoV-2 infection admitted to the City North Campus of Urumqi First People's Hospital from October to December 2022 were retrospectively reviewed.@*RESULTS@#All 23 infants had a history of exposure to confirmed caregivers with SARS-CoV-2 infection after birth, and none of them was vertically transmitted. Clinical classification: 5 cases of asymptomatic infection, 18 cases of mild infection, and no cases of moderate, severe, or critically ill. The first symptoms were fever in 13 cases, cough in 3 cases, nasal congestion in 1 case, and diarrhea in 1 case. Blood white blood cell counts decreased in 2 cases, and C-reactive protein increased in 1 case. Seven infants underwent chest X-ray examination due to cough or shortness of breath, and one of which showed focal exudative changes, while the rest showed no abnormal changes. All infants were discharged after symptomatic treatment and the median hospital stay was 6 days. The duration of nucleic acid positivity of SARS-CoV-2 was negatively correlated with N gene Ct values and ORF1ab gene Ct values (rs=-0.719 and -0.699, respectively; P<0.05). One month after discharge, all infants had no symptoms or signs of nucleic acid re-positivity.@*CONCLUSIONS@#The clinical manifestations are usually mild or asymptomatic in neonates infected with SARS-CoV-2 Omicron variant. The lower the Ct values of the N and ORF1ab genes of SARS-CoV-2, the longer the duration of nucleic acid positivity. Neonates infected with SARS-CoV-2 Omicron variant can have a good prognosis after symptomatic treatment.

Dupilumab for Treatment of Food-Dependent, Exercise-Induced Anaphylaxis: Report of One Case / 中国医学科学杂志(英文版)

Food-dependent, exercise-induced anaphylaxis (FDEIA) is a potentially life-threatening disorder that often occurs with exercise, and patients typically have eaten a specific food within hours before disease onset. This disease is exceedingly rare, with a prevalence of 0.02%. No well-recognized prevention or treatment strategy has been available for FDEIA except avoiding triggers strictly. Here we report an 11-year-old boy with a history of recurrent anaphylaxis of unknown etiology more than 10 times within two years. As the anaphylactic symptoms had not been controlled after traditional treatments, the patient was given subcutaneous injection of dupilumab seven times within 33 weeks. During dupilumab treatments, the patient was exposed to culprit mushrooms plus exercises at least twice a month but without notable anaphylaxis. Thus, Dupilumab may improve the allergic reactions in FDEIA patients.

Research on classification method of multimodal magnetic resonance images of Alzheimer's disease based on generalized convolutional neural networks / 生物医学工程学杂志

Alzheimer's disease (AD) is a progressive and irreversible neurodegenerative disease. Neuroimaging based on magnetic resonance imaging (MRI) is one of the most intuitive and reliable methods to perform AD screening and diagnosis. Clinical head MRI detection generates multimodal image data, and to solve the problem of multimodal MRI processing and information fusion, this paper proposes a structural and functional MRI feature extraction and fusion method based on generalized convolutional neural networks (gCNN). The method includes a three-dimensional residual U-shaped network based on hybrid attention mechanism (3D HA-ResUNet) for feature representation and classification for structural MRI, and a U-shaped graph convolutional neural network (U-GCN) for node feature representation and classification of brain functional networks for functional MRI. Based on the fusion of the two types of image features, the optimal feature subset is selected based on discrete binary particle swarm optimization, and the prediction results are output by a machine learning classifier. The validation results of multimodal dataset from the AD Neuroimaging Initiative (ADNI) open-source database show that the proposed models have superior performance in their respective data domains. The gCNN framework combines the advantages of these two models and further improves the performance of the methods using single-modal MRI, improving the classification accuracy and sensitivity by 5.56% and 11.11%, respectively. In conclusion, the gCNN-based multimodal MRI classification method proposed in this paper can provide a technical basis for the auxiliary diagnosis of Alzheimer's disease.

Construction of hiPSC-derived Excitatory Neural Network-like Tissue / 中山大学学报(医学科学版)

ObjectiveTo construct a neural network-like tissue with the potential of synaptic formation in vitro by seeding human induced pluripotent stem cell-derived neural precursor cells （hiPSC-NPCs） on decellularized optic nerve （DON）， so as to provide a promising approach for repair of nerve tissue injury. MethodsThrough directional induction and tissue engineering technology， human induced pluripotent stem cells （hiPSCs） and 3D DON scaffolds were combined to construct neural network-like tissues. Then the hiPSCs were directionally induced into human neural precursor cells （hNPCs） and neurons. Immunofluorescence staining was used to identify cell differentiation efficiency. 3D DON scaffolds were prepared. Morphology and cytocompatibility of scaffolds were identified by scanning electron microscopy and Tunnel staining. Induced hiPSC-NPCs were seeded on DON scaffolds. Immunofluorescence staining， scanning electron microscopy， transmission electron microscopy and patch clamp were used to observe the morphology and functional identification of constructed neural network tissues. Results①The results of immunofluorescence staining suggested that most of hiPSC-NPCs differentiated into neurons in vitro. We had successfully constructed a neural network dominated by neurons. ② The results of scanning electron microscopy and immunohistochemistry suggested that a neural network-like tissue with predominating excitatory neurons in vitro was successfully constructed. ③The results of immunohistochemical staining， transmission electron microscopy and patch clamp indicated that the neural network-like tissue had synaptic transmission function. ConclusionA neural network-like tissue mainly composed of excitatory neurons has been constructed by the combination of natural uniform-channel DON scaffold and hiPSC-NPCs， which has the function of synaptic transmission. This neural network plays a significant role in stem cell derived replacement therapy， and offers a promising prospect for repair of spinal cord injury （SCI） and other neural tissue injuries.

Research progress on triterpenoids of Betula plants / 药学学报

The secondary metabolites of plants are important sources of natural drugs. Betula plants have abundant pharmacological value, complex mechanism and wide applications, which are closely related to the triterpenoids of theirs. Triterpenoids in Betula species are mainly divided into dammarane-type, ocotillol-type, oleanane-type, lupane-type and cycloaltunane-type. The extracts of Betula species have varieties of activities such as anti-tumor, anti-inflammatory, anti-oxidant, anti-bacterial, etc. And the biosynthetic pathways of triterpenoids after 2,3-oxidosqualene are split into four branches of dammarenediol-II, lupeol, cycloartenol and amyrin according to the different oxidosqualene cyclases. This review summarizes the chemical constituents, pharmacological activities and biosynthetic pathways of triterpenoids in Betula plants. It provides a reference for the research and development of new drugs and the production of these triterpenoids in microbial cell factories by synthetic biology methods.

Value of total bilirubin rebound rate and total bilirubin clearance rate in evaluating the prognosis of severe drug-induced liver injury after artificial liver support therapy / 临床肝胆病杂志

Objective To investigate the value of total bilirubin rebound rate (TBRR), total bilirubin clearance rate (TBCR), and TBCR after 1 week of treatment (ΔTBCR) in evaluating the short-term prognosis of patients with severe drug-induced liver injury (DILI) after artificial liver support therapy. Methods A retrospective analysis was performed for 203 patients with severe DILI who received artificial liver support therapy in Tianjin Third Central Hospital from September 2013 to December 2021, and general information, biochemical parameters, and clinical classification were collected. The patients were divided into improved group and unhealed group according to the prognosis at discharge, and Model for End-Stage Liver Disease (MELD) score, TBRR, TBCR, and ΔTBCR were calculated. The independent samples t -test was used for comparison of normally distributed continuous data between groups, and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between groups; the chi-square test was used for comparison of categorical data between groups. The receiver operating characteristic (ROC) curve was plotted to investigate the value of assessment indices in predicting the prognosis of patients, and the Kaplan-Meier method was used to investigate the difference in the length of hospital stay in the context of different assessment indices. Results Compared with the unhealed group, the improved group had significantly lower age ( t =-2.762, P < 0.05), white blood cell count ( Z =-3.184, P < 0.05), total bilirubin ( t =-2.809, P < 0.05), conjugated bilirubin ( t =-2.739, P < 0.05), international normalized ratio ( Z =-2.357, P < 0.05), MELD score ( t =-3.090, P < 0.05), and TBRR ( t =-4.749, P < 0.05), as well as significantly higher albumin ( t =2.198, P < 0.05), prothrombin time activity ( t =2.018, P < 0.05), TBCR ( t =2.166, P < 0.05), and ΔTBCR ( t =9.549, P < 0.05). MELD score, TBRR, TBCR, and ΔTBCR had an area under the ROC curve (AUC) of 0.656, 0.727, 0.611, and 0.879, respectively, and ΔTBCR had a better predictive value than TBRR ( Z =3.169, P =0.001 5). The optimal cut-off value was 22.5% for TBRR (with a sensitivity of 94.6% and a specificity of 45.2%) and 27.4% for ΔTBCR (with a sensitivity of 77.7% and a specificity of 86.5%). ΔTBCR showed a good predictive value in different clinicopathological types, with extremely high sensitivity (91.4%) and specificity (100.0%) in evaluating the treatment outcome of patients with mixed-type DILI after artificial liver support therapy. Conclusion TBRR and ΔTBCR have a higher value than MELD score in evaluating the short-term prognosis of patients with severe DILI after artificial liver support therapy, among which ΔTBCR has a higher predictive value.

The Molecular Mechanism of LncRNA HOTAIR Regulating the Proliferation, Invasion and Migration of Lymphoma Cells through Target Gene miR-20a-5p / 中国实验血液学杂志

OBJECTIVE@#To investigate the effects of lncRNA HOTAIR on the proliferation, invasion and migration of lymphoma cells through target gene miR-20a-5p and its molecular mechanism.@*METHODS@#After synthesizing HOTAIR siRNA and siRNA NC plasmids, they were transfected into lymphoma Raji cells, respectively. The expression of HOTAIR mRNA was detected by RT-qPCR. The proliferation, invasion and migration of lymphoma Raji cells were detected by CCK-8 assay, Transwell assay and cell scratch healing assay, respectively. The target gene of lncRNA HOTAIR was predicted by miRcode software, and the relationship between HOTAIR and target gene was analyzed by dual luciferase assay. After synthesis of miR-20a-5p inhibitor and inhibitor NC, Raji cells were transiently transfected. The expression of miR-20a-5p was detected by RT-qPCR, and the effects of down-regulation of miR-20a-5p on the proliferation, invasion and migration of Raji cells were analyzed. The overexpression plasmid of lncRNA HOTAIR and miR-20a-5p mimics were transfected into Raji cells simultaneously to analyze the proliferation, invasion and migration ability of Raji cells. After overexpression or down-regulation of miR-20a-5p, the expression of JAK/STAT3 signaling pathway related proteins was analyzed.@*RESULTS@#HOTAIR expression in Raji cells was decreased after transfection of HOTAIR siRNA (P<0.01), and miR-20a-5p expression was also decreased after transfection of miR-20a-5p inhibitor (P<0.01). HOTAIR had a targeting and negative regulation relationship with miR-20a-5p (r=-0.826). Silencing HOTAIR promoted the expression of miR-20a-5p and inhibited the proliferation, invasion and migration of Raji cells. Down-regulation of miR-20a-5p expression promoted the proliferation, invasion and migration of Raji cells. Effect of HOTAIR overexpression on the proliferation, invasion and migration of Raji cells could be reversed by up-regulation of miR-20a-5p. Down-regulation of miR-20a-5p expression activated the intracellular JAK/STAT3 signaling pathway.@*CONCLUSION@#HOTAIR affects the proliferation, invasion and migration of lymphoma cells by targeting miR-20a-5p, and its mechanism may be related to the activation of JAK/STAT3 signaling pathway.

Role of CD4+NKG2D+ T cells in the disease activity of juvenile idiopathic arthritis / 中国当代儿科杂志

OBJECTIVES@#To study the expression levels of CD4+NKG2D+ T cells and NKG2D soluble ligands, the soluble MHC class I chain-related molecules A and B (sMICA/sMICB) in the active stage and stable stage of juvenile idiopathic arthritis (JIA) and their role in the disease activity of JIA.@*METHODS@#Nineteen children with systemic JIA and 20 children with articular JIA who were diagnosed in Children's Hospital of Chongqing Medical University from November 2019 to December 2021 were enrolled in this prospective study. Six healthy children were enrolled as the control group. After peripheral blood samples were collected, ELISA was used to measure the levels of sMICA and sMICB, and flow cytometry was used to measure the percentage of CD4+NKG2D+ T cells. Systemic Juvenile Arthritis Disease Activity Score-27 (sJADAS-27)/Juvenile Arthritis Disease Activity Score-27 (JADAS-27) was used to evaluate the disease activity in children with JIA. The Pearson correlation analysis and the receiver operating characteristic (ROC) curve were used to assess the role of CD4+NKG2D+ T cells, sMICA and sMICB in the disease activity of JIA.@*RESULTS@#The active systemic JIA and active articular JIA groups had a significant increase in the percentage of CD4+NKG2D+ T cells compared with the control group and their corresponding inactive JIA group (P<0.05). The JIA groups had significantly higher levels of sMICA and sMICB than the control group (P<0.05), and the active articular JIA group had a significantly higher level of sMICB than the stable articular JIA group (P<0.05). In the children with JIA, the percentage of CD4+NKG2D+ T cells and the levels of sMICA and sMICB were positively correlated with sJADAS-27/JADAS-27 disease activity scores (P<0.05). The ROC curve analysis showed that sMICB had an area under the curve of 0.755 in evaluating the disease activity of JIA, with a specificity of 0.90 and a sensitivity of 0.64.@*CONCLUSIONS@#The percentage of CD4+NKG2D+ T cells and the levels of sMICA and sMICB increase in children with JIA compared with healthy children and are positively correlated with the disease activity of JIA, suggesting that CD4+NKG2D+ T cells and NKG2D ligands can be used as potential biomarkers for evaluating the disease activity of JIA.

Misdiagnosis of angiosarcoma of foot as diabetic foot ulcer: One case report and review of literature / 中华内分泌代谢杂志

Angiosarcoma is a rare malignant tumor of soft tissue in adults. However, tumor ulcers caused by foot angiosarcoma are rarely reported in the literature. This paper outlines a case of foot angiosarcoma misdiagnosed as diabetic foot ulcer. It was treated as diabetic foot ulcer in other hospitals without notable improvement. In consideration of its special clinical characteristics and treatment process, pathological biopsy was performed after admission, and angiosarcoma was confirmed. The purpose of this article is to emphasize that foot angiosarcoma or other tumor ulcers in diabetes patients are easily misdiagnosed as diabetic foot ulcers. If there is no obvious improvement in treatment, pathological tissue biopsy should be performed as early as possible.