Dihydroartemisinin Suppresses Proliferation of Oral Squamous Cell Carcinoma Cells by Promoting Autophagy / 肿瘤防治研究

Objective To investigate the effect of dihydroartemisinin (DHC) on the proliferation capacity of human oral squamous carcinoma cells and its mechanism of action. Methods The viability and colony formation ability of CAL27 cells treated with different concentrations of dihydroartemisinin was measured by CCK-8 and colony formation assay. The expression of proteins related to proliferation and autophagy was determined by Western blot. Potential targets for DHA inhibition of the biological behavior of oral cancer were screened based on network pharmacology and bioinformatics. Measurement was conducted after the cells were cotreated with autophagy blocker 3-methyladenine and autophagy inducers rapamycin and dihydroartemisinin. Results Dihydroartemisinin significantly reduced the proliferation viability and clone formation ability of CAL27 cells in a concentration-dependent manner. The PCNA expression level also decreased substantially. DHA suppressed oral cancer targets involving autophagy-related pathways. DHA intervention increased the expression of intracellular autophagy-related proteins Beclin-1 and LC3. After co-treatment of DHA combined with autophagy blocker, the proliferation viability and clone formation ability of CAL27 cells decreased. The expression of PCNA increased, and the expression of Beclin-1 and LC3 decreased. Conclusion Dihydroartemisinin could inhibit the proliferative capacity of oral squamous carcinoma cells in vitro, and its effect may be correlated with the induction of autophagy.

Herbal Textual Research on Farfarae Flos in Famous Classical Formulas / 中国实验方剂学杂志

By consulting ancient and modern literature， the herbal textual research of Farfarae Flos has been conducted to verify the name， origin， producing area， quality evaluation， harvesting and processing methods， so as to provide reference for the development and utilization of the famous classical formulas containing Farfarae Flos. According to the research， the results showed that Farfarae Flos was first described as a medicinal material by the name of Kuandonghua in Shennong Bencaojing（《神农本草经》）， and the name was used and justified by later generations. The main origin was the folwer buds of Tussilago farfara， in addition， the flower buds of Petasites japonicus were used as medicine in ancient times. The ancient harvesting time of Farfarae Flos was mostly in the twelfth month of the lunar calendar， and the modern harvesting time is in December or before the ground freeze when the flower buds have not been excavated. Hebei， Gansu， Shaanxi are the authentic producing areas with the good quality products. Since modern times， its quality is summarized as big， fat， purple-red color， no pedicel is better. Processing method from soaking with licorice water in the Northern and Southern dynasties to stir-frying with honey water followed by micro-fire in the Ming dynasty， and gradually evolved to the modern mainstream processing method of honey processing. Based on the research results， it is suggested that the dried flower buds of T. farfara， a Compositae plant， should be selected for the development of famous classical formulas containing Farfarae Flos， and the corresponding processed products should be selected according to the specific processing requirements of the formulas， and raw products are recommended for medicinal use without indicating processing requirements.

Mechanism of levosimendan in treating hypoxic pulmonary hypertension based on network pharmacology and molecular docking technology / 中国药理学通报

Aim To explore the efficacy of levosimendan on hypoxia pulmonary hypertension through animal experiments, and to further explore the potential mechanism of action using network pharmacological methods and molecular docking technique. Methods The rat model of hypoxia pulmonary hypertension was constructed to detect right heart systolic pressure and right heart remodeling index. HE , Masson, and VG staining were core targets were screened out. GO and KEGG pathway enrichment analysis were performed using the DAVID database. Molecular docking of the core targets was performed with the AutoDock software. Results The results of animal experiments showed that levosimendan had obvious therapeutic effect on hypoxia pulmonary hypertension. The network pharmacology results showed that SRC, HSP90AA1, MAPK1, PIK3R1, AKT1, HRAS, MAPK14, LCK, EGFR and ESR1 used to analyze the changes of rat lung histopathology. Search the Swiss Target Prediction, DrugBank Online, BatMan, Targetnet, SEA, and PharmMapper databases were used to screen for drug targets. Disease targets were retrieved from the GeneCards, OMIM databases. The "drug-target-disease" network was constructed after identification of the two intersection targets. The protein interaction network was constructed and the were the key targets to play a therapeutic role. Molecular docking showed good docking of levosimendan with all the top five core targets with degree values. Conclusions Levosimendan may exert a therapeutic effect on hypoxia-induced pulmonary hypertension through multiple targets.

Association between obesity and dyslipidemia among rural primary and middle school students in Students Nutrition Improvement Program Areas of Zhejiang Province / 中国学校卫生

Objective@#The study aimed to analyze the association between different types of obesity and dyslipidemia among rural primary and middle school students in Zhejiang Province, so as to inform strategies for prevention and control of childhood obesity and hyperlipidemia.@*Methods@#As part of Nutrition Improvement Programme for Rural Compulsory Education Students, 1 244 participants were selected by stratified cluster random sampling in 5 counties of Zhejiang Province during September to December 2021. Physical examination, detection of blood lipid and questionnaire survey were conducted. The Chi -square test and Logistic regression analyses were used to assess the association between different types of obesity and dyslipidemia.@*Results@#The prevalence rates of overweight, obesity, abdominal obesity, and hyperlipidemia were 15.11%, 12.46%, 17.60%, and 21.78%. Obesity and abdominal obesity were correlated to high risk of high triglycerides ( OR =3.97, 95% CI =2.54-6.20; OR =4.45, 95% CI =2.95- 6.72 )( P <0.05). Compared with the non overweight and obese group with normal waist circumference,the overweight and obesity group were correlated to high risk of high cholesterol ( OR=2.53, 95%CI =1.45-4.42, P <0.05). Abdominal overweight or obese group had the highest risk for dyslipidemia and triglycerides ( OR =1.82, 95% CI =1.33-2.48; OR =3.64, 95% CI =2.45-5.43) ( P < 0.05).@*Conclusions@#The prevalence rates of overweight, obesity, abdominal obesity, and hyperlipidemia are relatively high in rural primary and middle school students of Nutrition Improvement Programme for Rural Compulsory Education Students in Zhejiang Province. Abdominal obesity is a more important risk factor for hyperlipidemia. Waist circumference should be the focus of considerable attention.

Herbal Textual Research on Asteris Radix et Rhizoma in Famous Classical Formulas / 中国实验方剂学杂志

By reviewing the ancient and modern literature， the name， origin， scientific name evolution， place of origin， quality， harvesting， processing， efficacy and toxicity of Asteris Radix et Rhizoma（ARR） were systematically sorted out， so as to provide reference for the development and utilization of the relevant famous classical formulas. According to textual research， ARR was first contained in Shennong Bencaojing， all generations are Ziwan for its proper name， and there are still aliases such as Ziyuan， Ziqian and Xiaobianer. Its mainstream origin in successive generations was Aster tataricus， and there are also Ligularia fischeri and others in local area of use. The medicinal parts of ARR are root and rhizome， but in modern times， the rhizome is mostly used for propagation and cultivation， so some of ARR medicinal materials only have the root without the rhizome. The earliest recorded ancient origin of ARR was now Fangxian（Hubei）， Zhengding and Handan（Heibei）， then the range of production areas gradually expanded， the mainstream production areas from the Song dynasty to the Ming and Qing dynasties included Hebei， Jiangsu， Anhui， Henan and other places， since modern times， two major producing areas have been formed in Anguo， Hebei province and Bozhou， Anhui province. From the quality evaluation， it is clear that from ancient times， flexible roots and purple color are the best. The ancient harvesting was mainly in lunar February or March， and then dried in the shade， and the modern harvesting is mostly in spring and autumn， and the roots are braided into pigtails and then dried in the sun or dried in the sun after 1-2 d. The ancient and modern processing method of ARR are basically the same， mainly honey processing， there are still methods of frying， steaming， vinegar sizzling， etc. Based on the results， it is recommended that the dried roots and rhizomes of A. tataricus should be used in clinical and the development of related famous classical formulas， and those whose original formulas specify the processing requirements can be processed according to the relevant requirements， while whose processing requirements are not specified should be used in the form of raw products.

Clinical observation of early-onset antinuclear antibody-positive juvenile idiopathic arthritis / 中华微生物学和免疫学杂志

Objective:To investigate the clinical features, treatment and follow-up of children with early-onset antinuclear antibody (ANA)-positive juvenile idiopathic arthritis (JIA).Methods:Eighty-six oligoarticular JIA patients with early-onset arthritis (≤6 years old) admitted to the Children′s Hospital Affiliated to Capital Institute of Pediatrics from January 2017 to December 2019 were included in this study. According to ANA titer, these patients were divided into two groups: ANA-positive group (44 cases) and ANA-negative group (42 cases). Clinical data including demographic data, clinical features, laboratory testing results, treatment and follow-up data were statistically analyzed.Results:The ratio of male to female was 7∶37 in the ANA-positive group and 15∶27 in the ANA-negative group and there was significant difference between the two groups ( P=0.035). The proportions of patients with increased C-reactive protein and erythrocyte sedimentation rate were higher in the ANA-positive group than in the ANA-negative group [18.18% (8/44) vs 16.67% (7/42) and 29.55% (13/44) vs 19.05% (8/42), both P>0.05]. The most commonly involved joints in the ANA-positive group were knee (95.45%, 42/44), ankle (20.45%, 9/44) and wrist (18.18%, 8/44), and unilateral asymmetric joint involvement accounted for 81.8% (36/44). In the ANA-negative group, the involved joints were knee (85.71%, 36/42), ankle (14.29%, 6/42), wrist (14.29%, 6/42) and hip (11.90%, 5/42), and 27 out of the 42 cases (64.29%) had unilateral asymmetric joint involvement. There was no significant difference in the above indexes between the two groups (all P>0.05). There were seven cases (15.91%) with uveitis in the ANA-positive group and two cases (4.76%) in the ANA-negative group, and the difference between the two groups was significant ( P=0.045). Before treatment, the ANA-positive group had a significantly higher disease activity score (JADAS27) than the ANA-negative group (14.43±2.87 vs 12.09±3.32, P=0.002). After treatment, the JADAS27 score in both groups decreased (both P<0.05). After six months of treatment, the two groups had similar clinical remission rates [70.45% (31/44) vs 76.19% (32/42), P>0.05]. Conclusions:Early-onset ANA-positive JIA was more common in female children, and asymmetric knee joint involvement was the most common clinical manifestation. The incidence of ophthalmic complications was high, and ophthalmological examination should be performed more frequently during follow-up. The prognosis of early-onset ANA-positive JIA was good with early treatment. Positive ANA was not a risk factor for poor prognosis.

Clinical characteristics of infantile Takayasu arteritis complicated with cardiac involvements / 中华风湿病学杂志

Objective:To analyze the clinical characteristics of infantile Takayasu Arteritis (TAK) complicated with cardiac involvements.Methods:The clinical data and cardiac lesions of infantile TAK were collected retrospectively, and the clinical characteristics of the disease were analyzed and summarized. Mainly using decriptive statistical methods.Results:In these 20 cases, 16 cases (80%) had cardiac involvements, only 2 cases had related symptoms. The common lesions were coronary artery lesion (CAL), valvular disease, and elevated myocardial enzymes, while the rare lesions were arrhythmia, pericardial effusion, hypertensive heart disease, and heart failure. One case had acute heart failure, which was systolic heart failure and was accompanied by hypertensive heart disease. All 14 patients with CAL were found by conventional coronary ultrasound screening. A total of 39 CAL were found, all of which were coronary artery dilation, and the left main coronary artery was involved. Five patients had heart valve disease, all of them were valve insufficiency. The involved valves were mitral and tricuspid valves, and one of them was severe insufficiency. Arrhythmias were found in 2 cases, of which P1 was found to have paroxysmal atrial tachycardia with high atrioventricular block at 3 months. All 20 children survived and were in stable condition after being treat with biological agents and/or glucocorticoids. A case of hypertensive heart disease complicated with heart failure was followed up for 4 years, and the cardiac function and blood pressure returned to normal. Fourteen children with CAL lesions were given oral aspirin disease, the CALs disappeared in 10 cases and retracted in 4 cases. During the follow-up of 5 children with heart valves, insufficiency disappeared in 4 cases and improved in 1. No child underwent valve replacement during the follow-up. One of the children with arrhythmia was treated with antiarrhythmic drugs. After treatment, the arrhythmia disappeared. Now they have been followed up for 5 years without recurrence.Conclusion:Infantile TAK has a high incidence of heart involvement, with extensive lesions but insidious clinical symptoms. CALs are common, and heart failure is rare. It should be evaluated and treated as early as possible.

The application of blended learning in clinical practice of college students majoring in medical imaging diagnosis / 中华医学教育探索杂志

Objective:To explore the application effect of blended learning in clinical practice of undergraduate students majoring in medical imaging diagnosis.Methods:A total of 60 undergraduate students majoring in medical imaging diagnosis who practiced in the Department of Radiology of Chongqing General Hospital from 2017 to 2019 were selected as subjects. The students were divided into experimental group and control group, each with 30 students. During the internship, the experimental group adopted the blended learning, including lecture-based learning, case-based learning, problem-based learning and team-based learning according to different teaching scenarios. While the control group adopted the traditional teaching mode. At the end of the internship, the test scores of the two groups of intern students were compared, and the satisfaction degree of the teaching was investigated by questionnaire. SPSS 19.0 was used to conduct t-test and Chi-square test. Results:The score of theoretical knowledge examination in the experimental group was (90.27±5.38) points, and that in the control group was (83.13±7.57) points. The difference between the two groups was statistically significant ( t=4.21, P<0.001). The score of imaging analysis examination in the experimental group was (90.07 ± 4.80) points, and that in the control group was (82.13±8.71) points. The difference between the two groups was statistically significant ( t=4.37, P<0.001). The results of the satisfaction survey showed that the overall satisfaction with teaching was 76.7% (23/30) in the experimental group and 50.0% (15/30) in the control group, with statistically significant difference ( χ2= 6.57, P=0.037). Conclusion:The blended learning has a good effect in the teaching of undergraduate students majoring in medical imaging diagnosis.

Clinical characteristics of patients with diabetes complicated with pruritus / 中华内分泌外科杂志

Type 2 diabetes mellitus (T2DM) is a common chronic disease characterized by hyperglycemia. Itchy skin is common in patients with diabetes, and high blood sugar leads to decreased immunity and nerve damage, causing skin problems. 40 patients with T2DM complicated with pruritus diagnosed and treated in our hospital from March 2022 to September 2022 were included to observe the clinical characteristics of the patients.

Preparation of an ophthalmic formulation of TPGS-modified insulin-loaded liposomes and its in vitro corneal permeation and pharmacokinetics in rabbit eyes / 南方医科大学学报

OBJECTIVE@#To prepare vitamin E polyethylene glycol 1000 succinate (TPGS)-modified insulin-loaded liposomes (T-LPs/INS) and evaluate its safety, corneal permeability, ocular surface retention and pharmacokinetics in rabbit eyes.@*METHODS@#The safety of the preparation was investigated in human corneal endothelial cells (HCECs) using CCK8 assay and live/dead cell staining. In the ocular surface retention study, 6 rabbits were randomized into 2 equal groups for application of fluorescein sodium dilution or T-LPs/INS labeled with fluorescein in both eyes, which were photographed under cobalt blue light at different time points. In the cornea penetration test, another 6 rabbits divided into 2 groups for application of Nile red diluent or T-LPs/INS labeled with Nile red in both eyes, after which the corneas were harvested for microscopic observation. In the pharmacokinetic study, 2 groups of rabbits (n=24) were treated with eye drops of T-LPs/INS or insulin, and the aqueous humor and cornea were collected at different time points for measurement of insulin concentrations using enzyme linked immunosorbent assay. DAS2 software was used to analyze the pharmacokinetic parameters.@*RESULTS@#The prepared T-LPs/INS showed good safety in cultured HCECs. Corneal permeability assay and fluorescence tracer ocular surface retention assay demonstrated a significantly higher corneal permeability of T-LPs/INS with a prolonged drug residence in the cornea. In the pharmacokinetic study, insulin concentrations in the cornea at 6, 15, 45, 60, and 120 min (P < 0.01) and in the aqueous humor at 15, 45, 60, and 120 min after dosing were significantly higher in T-LPs/INS group. The changes in insulin concentrations in the cornea and aqueous humor were consistent with a two-compartment model in T-LPs/INS group and with the one-compartment model in the insulin group.@*CONCLUSION@#The prepared T-LPs/INS shows an improved corneal permeability, ocular surface retention capacity and eye tissue concentration of insulin in rabbits.

Screening and identification of CD44v9 specific peptide ligand for gastric cancer detection / 西安交通大学学报(医学版)

【Objective】 To screen and verify a peptide ligand specific for CD44v9. 【Methods】 A 12-mer phage peptide library was screened on CD44v9 coated on solid phase. Candidate sequences emerged after sequencing. Candidate phages were selected using enzyme-linked immunosorbent assay. The best sequence was chosen for further study. Binding of C9-3 to CD44v overexpressed HEK-293 cells was determined using immunofluorescence. Binding affinity and specificity were verified on gastric cancer tissues with immunohistochemistry. 【Results】 Phages significantly were enriched during panning process. After sequencing, nine individual sequences occurred in 30 selected clones. Among the 9 candidate sequences, C9-3 exhibited the highest frequency. Results of ELISA showed that C9-3 had the highest OD value and selectivity. Thus, C9-3 was chosen for peptide probe synthesis. C9-3 probe stained CD44v overexpressed HEK-293 cells, but not empty vector transfected HEK-293 cells. Immunohistochemistry scores of C9-3 were significantly different between gastric cancer and paracancer tissues (t=3.953, P<0.01). A linear positive correlation was observed between C9-3 binding and CD44v9 expression (r=0.823, P<0.01). 【Conclusion】 In this study, peptide ligand of CD44v9 was successfully screened. The peptide can bind to cells and cancer tissues via CD44v9. It has potential for gastric targeting probes.

Neuroprotective and mechanistic study of GJ-4 on okadaic acid-induced memory impairment in mice / 药学学报

GJ-4 is crocin enrichments extracted from Gardenia jasminoides J. Ellis, and our previous studies have shown that GJ-4 significantly improved learning and memory impairment induced by Aβ in mice. Herein, a memory deficit model was developed by injecting okadaic acid (OA) into the lateral ventricle of mice, and the neuroprotection and underlying mechanism of GJ-4 on neuronal injury caused by Tau hyperphosphorylation were investigated. The Animal Care & Welfare Committee, Institute of Materia Medica, CAMS & PUMC has approved all procedures (No.00000318). GJ-4 at different doses was intragastric administration to mice for 16 days. Step-down test and Morris water maze test showed that GJ-4 could significantly improve OA-induced memory impairment in mice, and reduced the loss of Nissl bodies in the hippocampus of mice. GJ-4 could also decrease the phosphorylation level of Tau protein at Ser396, Thr231 and Ser404 via increasing protein phosphatase 2A (PP2A) activity and inhibiting glycogen synthase kinase-3β (GSK-3β) activity. Besides, further researches indicated that GJ-4 could inhibit the level of oxidative stress in the brain of OA mice, reduce neuronal apoptosis and inhibit the neuroinflammation mediated by activation of astrocytes in the hippocampus of mice, and eventually achieve its effects in improving learning and memory impairment in mice. According to these findings, we anticipated that GJ-4 might be a potential therapeutic drug for Alzheimer's disease.

Research progress of bacterial biofilm eradication agents based on modifications of natural products / 药学学报

Bacterial biofilm widely exists in all kinds of bacteria, and is related to about 80 percent of bacterial infections. It is one of the main reasons for bacterial tolerance and resistance to existing antibiotics. Therefore, there is unmet clinical need for new anti-biofilm drugs. At present, there are three kinds of anti-biofilm agents under research, including biofilm inhibitors, biofilm dispersal agents and biofilm eradication agents. Among them, the biofilm eradication agent is unique, which can not only kill bacteria in biofilm but also eliminate biofilm as a monotherapy. Based on modifications of natural products with antibacterial activity, a variety of compounds with biofilm eradicating activities have been obtained, such as, acyldepsipeptides, pyrrolomycins, halogenated phenazines and halogenated 8-hydroxyquinolines. In this review, we summarize several major biofilm eradication agents above according to their structures and mechanisms.

Clinical and imaging features of infective sacroiliitis in children / 中华儿科杂志

Objective: To summarize the clinical, radiological characteristics, and prognosis of infectious sacroiliitis in children. Methods: A case-control study was conducted, including 12 cases of infectious sacroiliitis diagnosed in the Rheumatology and Immunology Department of the Children's Hospital affiliated with the Capital Institute of Pediatrics from June 2018 to June 2023. These cases comprised the case group. Concurrently, 28 cases of pediatric idiopathic arthritis involving the sacroiliac joint in the same department served as the control group. Basic patient information, clinical features, laboratory parameters, and clinical treatment outcomes for both groups were collected and analyzed. Independent sample t-tests and chi-squared tests were used for inter-group comparisons. Results: Among the 12 cases in the case group, there were 5 males and 7 females, with a disease duration of 0.8 (0.5, 1.2) months. Nine patients presented with fever, and 1 patient had limping gait. Human leukocyte antigen (HLA)-B27 positivity was observed in 1 case, and there was no family history of ankylosing spondylitis. In the control group of 28 cases, there were 19 males and 9 females, with a disease duration of 7.0 (3.0, 17.0) months. One patient (4%) had fever, and 14 cases (50%) exhibited limping gait. HLA-B27 positivity was found in 18 cases (64%), and 18 cases (64%) had a family history of ankylosing spondylitis. The case group had higher white blood cell count (WBC), neutrophil ratio, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) levels, as well as a higher proportion of unilateral involvement on magnetic resonance imaging and bone destruction on CT compared to the control group ((11.1±6.2)×109 vs. (7.3±2.3)×109/L, 0.64±0.10 vs. 0.55±0.12, 72 (34, 86) vs. 18 (5, 41) mm/1 h, 24.6 (10.1, 67.3) mg/L vs. 3.6 (0.8, 15.0) mg/L, 11/12 vs. 36% (10/28), 9/12 vs. 11% (3/28), t=2.90, 3.07, Z=-2.94, -3.28, χ2=10.55, 16.53, all P<0.05). Conclusions: Pediatric infectious sacroiliitis often presents as unilateral involvement with a short disease history. Elevated WBC, CRP, and ESR, as well as a high rate of bone destruction, are also common characteristics.

Nodal T-follicular helper cell lymphoma, angioimmunoblastic-type associated with diffuse large B-cell lymphoma: a clinicopathological study / 中华病理学杂志

Objective: To investigate the clinicopathological features and molecular genetics of diffuse large B-cell lymphomas (DLBCL) with concurrent or secondary to nodal T-follicular helper cell lymphoma, angioimmunoblastic-type (nTFHL-AI). Methods: The clinicopathological features and molecular genetics of DLBCL associated with nTFHL-AI diagnosed between January 2015 and October 2022 at the First Affiliated Hospital of Zhengzhou University were analyzed using histology, immunohistochemistry, PCR, EBV-encoded RNA in situ hybridization and fluorescence in situ hybridization (FISH). Clinical information was collected and analyzed. Results: A total of 6 cases including 3 nTFHL-AI with secondary DLBCL and 3 composite lymphomas were reviewed. There were 4 male and 2 female patients, whose ages ranged from 40 to 74 years (median 57 years). All patients presented with nodal lesions at an advanced Ann Arbor stage Ⅲ/Ⅳ (6/6). Bone marrow involvement was detected in 4 patients. All cases showed typical histologic and immunophenotypic characteristics of nTFHL-AI. Among them, 5 cases of DLBCL with concurrent nTFHL-AI exhibited numerous large atypical lymphoid cells and the tumor cells were CD20 and CD79α positive. The only case of DLBCL secondary to nTFHL-AI showed plasma cell differentiation and reduced expression of CD20. All of cases were activated B-cell (ABC)/non-germinal center B-cell (non-GCB) subtype. Three of the 6 cases were EBV positive with>100 positive cells/high power field, meeting the diagnostic criteria of EBV+DLBCL. The expression of MYC and CD30 protein in the DLBCL region was higher than that in the nTFHL-AI region (n=5). C-MYC, bcl-6 and bcl-2 translocations were not detected in the 4 cases that were subject to FISH. Four of the 6 patients received chemotherapy after diagnosis. For the DLBCL cases of nTFHL-AI with secondary DLBCL, the interval was between 2-20 months. During the follow-up period ranging from 3-29 months, 3 of the 6 patients died of the disease. Conclusions: DLBCL associated with nTFHL-AI is very rare. The expansion of EBV-infected B cells in nTFHL-AI may progress to secondary EBV+DLBCL. However, EBV-negative cases have also been reported, suggesting possible other mechanisms. The up-regulation of MYC expression in these cases suggests a possible role in B-cell lymphomagenesis. Clinicians should be aware that another biopsy is still necessary to rule out concurrent or secondary DLBCL when nodal and extranodal lesions are noted after nTFHL-AI treatment.

Structure-based drug discovery of novel fused-pyrazolone carboxamide derivatives as potent and selective AXL inhibitors

As a novel and promising antitumor target, AXL plays an important role in tumor growth, metastasis, immunosuppression and drug resistance of various malignancies, which has attracted extensive research interest in recent years. In this study, by employing the structure-based drug design and bioisosterism strategies, we designed and synthesized in total 54 novel AXL inhibitors featuring a fused-pyrazolone carboxamide scaffold, of which up to 20 compounds exhibited excellent AXL kinase and BaF3/TEL-AXL cell viability inhibitions. Notably, compound 59 showed a desirable AXL kinase inhibitory activity (IC50: 3.5 nmol/L) as well as good kinase selectivity, and it effectively blocked the cellular AXL signaling. In turn, compound 59 could potently inhibit BaF3/TEL-AXL cell viability (IC50: 1.5 nmol/L) and significantly suppress GAS6/AXL-mediated cancer cell invasion, migration and wound healing at the nanomolar level. More importantly, compound 59 oral administration showed good pharmacokinetic profile and in vivo antitumor efficiency, in which we observed significant AXL phosphorylation suppression, and its antitumor efficacy at 20 mg/kg (qd) was comparable to that of BGB324 at 50 mg/kg (bid), the most advanced AXL inhibitor. Taken together, this work provided a valuable lead compound as a potential AXL inhibitor for the further antitumor drug development.

WDR62-deficiency Causes Autism-like Behaviors Independent of Microcephaly in Mice / 神经科学通报·英文版

Brain size abnormality is correlated with an increased frequency of autism spectrum disorder (ASD) in offspring. Genetic analysis indicates that heterozygous mutations of the WD repeat domain 62 (WDR62) are associated with ASD. However, biological evidence is still lacking. Our study showed that Wdr62 knockout (KO) led to reduced brain size with impaired learning and memory, as well as ASD-like behaviors in mice. Interestingly, Wdr62 Nex-cKO mice (depletion of WDR62 in differentiated neurons) had a largely normal brain size but with aberrant social interactions and repetitive behaviors. WDR62 regulated dendritic spinogenesis and excitatory synaptic transmission in cortical pyramidal neurons. Finally, we revealed that retinoic acid gavages significantly alleviated ASD-like behaviors in mice with WDR62 haploinsufficiency, probably by complementing the expression of ASD and synapse-related genes. Our findings provide a new perspective on the relationship between the microcephaly gene WDR62 and ASD etiology that will benefit clinical diagnosis and intervention of ASD.

Research progress of histone acetylation in prevention and treatment of heart failure and new ideas based on traditional Chinese medicine / 中国中药杂志

Chronic heart failure(CHF) has become a worldwide public health problem due to its high morbidity and mortality, which seriously endangers people's lifespan and quality of life. In recent years, the treatment strategy of CHF has shifted its emphasis on short-term improvement and transformation of hemodynamics to long-term repair as well as improvement of the biological properties of heart failure. At present, with the continuous deepening of medical research, it has been found that histone acetylation is closely related to the occurrence and development of CHF. Traditional Chinese medicine, via regulating histone acetylation, delays ventricular remodeling, improves energy metabolism, inhibits fibrosis and cardiomyocyte hypertrophy, and intervenes in the development process of heart failure, thus reducing the mortality and the readmission rate and ultimately improving long-term prognosis. Therefore, this study reviewed the mechanism of histone acetylation in the treatment of heart failure as well as its prevention and treatment with traditional Chinese medicine, to provide reference for clinical treatment of CHF.

Herbal Textual Research on Trichosanthis Fructus and Trichosanthis Radix in Famous Classical Formulas / 中国实验方剂学杂志

Through reviewing the ancient and modern literature， the name， origin， producing area， quality evaluation， harvesting and processing methods of Trichosanthis Fructus（TF） and Trichosanthis Radix（TR） in famous classical formulas were systematically sorted out following the chronological order. The results showed that there were many nicknames of TF and TR， and Gualou and Tianhuafen have become the mainstream names for its fruit and root， respectively. Both of them took Trichosanthes kirilowii as the mainstream base. TF and TR have been used as medicines in the Han dynasty， and since the North and South dynasties， Leigong Paozhilun had been clear that the effects of peels， seeds， stems， roots were different. TF was used as medicine with intact fruits， harvested after maturity from September to October， hung and dried in the shade， and its quality has been summarized in recent times as being best for those who are mature， large， thick and pliable peels， orange-yellow in color， and with sufficient sugary properties. In ancient times， the processing of TR was mostly crushed or shredded with the peels and seeds， or processing for pancakes and creams. TR was used as medicine with the roots， it is harvested from November to December， peeled and dried in the sun， and its quality was best when it was deep in the soil， large， white， powdery， firm and delicate with few muscles and veins， and it was considered to be toxic when it was born in briney land. Processing method of TR was to do powder into the medicine in the Tang dynasty， and gradually evolved into direct slicing use in the Ming and Qing dynasties. Since the modern era， the authentic producing areas of TF and TR were in the vicinity of Lingbao， Henan province， known as Anyang Huafen， and in modern times， there are well-known production areas such as Anguo， which produces Qihuafen， and Jinan， which produces Changqing Gualou. In the Song dynasty， there was a habit of substituting Trichosanthis Semen for the whole herb， which was later corrected by the materia medica in Ming dynasty. Based on the results， It is suggested that T. kirilowii be selected as the basal plant for the development of famous classical formulas involving TR and TF. In Qingjin Huatantang， Trichosanthis Semen is processed by stir-frying method， while TR and TF in other five formulas from the Catalogue of Ancient Famous Classical Formulas（The First Batch） were all used in raw form.

Herbal Textual Research on Stephaniae Tetrandrae Radix in Famous Classical Formulas / 中国实验方剂学杂志

By reviewing ancient materia medica， medical and prescription books， combined with modern literature， the textual research of Stephaniae Tetrandrae Radix has been conducted to verify the name， origin， producing area， harvesting and processing methods. Through textual research， the results show that the mainstream name of this herb recorded in the past dynasties is Fangji， which is also called Hanzhong Fangji because it is produced in Hanzhong city， and after the Tang dynasty， it was gradually divided into Hanfangji and Mufangji， and there is the saying that Han Zhushuiqi， Mu Zhufengqi. The names of Fenfangji and Guangfangji were first seen in the republic of China. In addition， Fenfangji was once distributed in Hankou， so it was also known as "Hanfangji"， which is easily confused with the traditional Hanzhong Fangji for short. Based on the original research， it is concluded that Aristolochia heterophylla（Hanzhong Fangji）is the mainstream of Stephaniae Tetrandrae Radix used in the Qing dynasty and before， and the application history of Cocculus orbiculatus can be traced back to before the Tang dynasty. After the Ming dynasty， Stephania tetrandra gradually became another main origin， and in the Republic of China， A. fangchi was used as a medicine for Stephaniae Tetrandrae Radix， but in modern times it was banned because it contained aristolochic acid as a toxic ingredient， and S. tetrandra has become the mainstream legal origin. The traditional production area of Hanzhong Fangji is Hanzhong， Shaanxi province， while today the mainstream of S. tetrandra is manly produced in Jiangxi and other places. Based on the quality evaluation research， the quality of Hanzhong Fangji is better with the radial texture of section used as radial solution， yellow solid and fragrant. Fenfangji with solid quality， white inside， powdered enough， less fiber and radiating texture is better. From the harvesting and processing research， the root of Fangji is mostly harvested in spring and autumn， and the outer bark should be removed in some literature. Before the Ming dynasty， this herb was dried in the shade， and after the Ming dynasty， it was dried in the sun. The modern production processing of Fangji is to harvest it in autumn， wash it， remove the rough bark， dry it to half dry， cut it into sections， and then cut it longitudinally if it is large， and dry it. Based on the results， combined with current studies on the toxicity of aristolochic acid and influencing factors such as commercial circulation， it is suggested that S. tetrandra should be used as the origin of Fangji， the processed products are selected according to the prescription requirements， and those without specified requirements can be processed by referring to the raw products in the 2020 edition of Chinese Pharmacopoeia.