Ligustilide delays senescence of auditory cortex in mice by inhibiting ferritinophagy / 中国药理学通报

Aim To investigate the mechanism of ligu aged 2 months of the same strain were used as the constilide (LIG) in delaying the senescence of auditory trol (Ctrl) group. Auditory brainstem response test was cortex and treating central presbycusis. Methods used to detect the auditory threshold of mice before and Forty C57BL/6J mice aged 13 months were randomly di after treatment. Levels of serum MDA and activity of vided into ligustilide low-dose(L-LIG) group, ligustil serum SOD were detected to display the level of oxidative ide medium-dose (M-LIG) group, ligustilide high-dose stress. The pathological changes of auditory cortex were (H-LIG) group and aging (Age) group, and 10 mice observed by HE staining. Ferroptosis was observed by

Robustness assessment of cardiovascular meta-analysis / 中国胸心血管外科临床杂志

@#Objective     To evaluate the robustness of cardiovascular meta-analysis with use of fragility index. Methods     By searching PubMed, EMbase, and Web of Science databases from 2018 to 2022, relevant literature on cardiovascular meta-analysis was systematically collected and the fragility indexes were calculated; Spearman correlation analysis was used to explore the relationship between fragility index and sample size, total number of events, effect size and its confidence interval width. Results     A total of 212 meta-analyses from 29 articles were included, with a median fragility index of 11 (5, 25), a median sample size of 10 301 (3 384, 48 330), and a median total number of events of 360 (129, 1 309). Most meta-analyses chose relative risk as the effect measure (179/212), and chose Mantel-Haenszel method (102/212) and random effects model (153/212). The fragility index was positively correlated with the sample size (rs=0.56, P<0.05) and the total number of events (rs=0.61, P<0.05), and negatively correlated with confidence interval width of the effect size (rs=−0.52, P<0.05). No statistically significant results were obtained in the correlation between the fragility index and effect size. Conclusion     The fragility indexes of cardiovascular meta-analyses published in comprehensive journals of high impact factors and professional cardiovascular journals are generally low, and therefore lack robustness. Fragility index is suggested to be reported in medical researches, assisting in explaining the P-value.

N-methyl-D-aspartic acid receptor/MAPK/cAMP-response element binding protein pathway mediating pain-related aversion in anterior cingulate cortex / 解剖学报

Objective To explore the mechanism of N-methyl-D-aspartic acid ( NMDA) receptor/MAPK/cAMPresponse element binding protein ( CREB) pathway involved in pain-related aversion mediated by anterior cingulate cortex. Methods A total of 42 healtlry SD rats were randomly divided into control group (Ctrl) , normal saline(NS) injection group (NS) , complete freund adjuvant (CFA) model group ( CFA ) , injected CFA into the soles of the foot and injected NS into rostral part of anterior cingulate cortex (rACC)group (CFA+NS) , injected NS into the soles of the foot and injected NS into rACC group (NS+NS) , injected CFA into the soles of the foot and injected NMDA receptor antagonist ( APV ) into rACC group (CFA+APV) , injected NS into the soles of the foot and injected APV into rACC group ( NS + APV ) with 6 rats in each group. Rats avoidance score was analysised and rat thermal foot contraction latency ( PWL) ws alserved, the expression of NMDA receptor in rACC region was detected by immunohistochemical staining, the expression of NMDA receptor, phosphorylated ERK( p-ERK) and phosphorylated CREB ( p - CREB ) in rACC region was detected by immunofluorescent staining, the number of Nissl bodies in rACC region was observed by Nissl staining, and the expression of NMDA receptor, MAPK, CREB, ERK, p-ERK, p-CREB, synaptosomal-associated protein 25 interaction protein 30 (SIP30) protein in rACCregion was detected by Western blotting, and Real-time PCR was used to detect the mRNA expression of NMDA receptor, MAPK, CREB and ERK in the rACC region. Results Compared with the Ctrl group, the avoidance score and PWL decreased significantly and the expression of NMDA receptor, MAPK and CREB increased significantly in the CFA group (P<0. 05). Compared with the CFA+NS group, the number of Nissl bodies in CFA+APV and NS+APV groups increased significantly, while the expression of NMDA receptor, MAPK, CREB, p-ERK and p-CREB decreased significantly in NS+NS and NS+APV groups (P<0. 05). Conclusion NMDA receptor-MAPK-CREB signal pathway in rACC is involved in painrelated aversion, and inhibition of NMDA can reduce pain-related negative aversion.

Angelica sinensis polysaccharide promotes stress erythropoiesis in mice caused by 5-FU / 中国药理学通报

Aim To investigate the effects of angelica sinensis polysaccharide (ASP) antagonizing 5-fluorou-raeil (5-FU) on spleen stress erythropoiesis in mice and its related mechanism. Methods C57BL/6J mice aged 6-8 weeks were randomly divided into control group, ASP group, 5-FU group and ASP + 5-FU group. The mouse body weight during the modeling pe-riod was recorded, and peripheral blood routine and the number of mononuclear cells in the bone marrow of femur were measured. Histopathology of spleen was de-tected, also the index and cellularity of spleen were analyzed. BFU-E of spleen mononuclear cells was counted. The number of F4/80

Analysis of prognostic factors of extranodal NK/T-cell lymphoma treated with pegaspargase/L-asparaginase: a multicenter retrospective study / 中华血液学杂志

Objective: To explore the prognostic factors of extracellular NK/T cell lymphoma (ENKTL) treated with pegaspargase/L-asparaginase. Methods: The clinical data of 656 ENKTL patients diagnosed at 11 medical centers in the Huaihai Lymphoma Working Group from March 2014 to April 2021 were retrospectively analyzed. The patients were randomly divided into two groups: a training set (460 cases) and a validation set (196 cases) at 7∶3, and the prognostic factors of the patients were analyzed. A prognostic scoring system was established, and the predictive performance of different models was compared. Results: Patients' median age was 46 (34, 57) years, with 456 males (69.5% ) and 561 nasal involvement (85.5% ). 203 patients (30.9% ) received a chemotherapy regimen based on L-asparaginase combined with anthracyclines, and the 5-year overall survival rate of patients treated with P-GEMOX regimen (pegaspargase+gemcitabine+oxaliplatin) was better than those treated with SMILE regimen (methotrexate+dexamethasone+cyclophosphamide+L-asparaginase+etoposide) (85.9% vs 63.8% ; P=0.004). The results of multivariate analysis showed that gender, CA stage, the Eastern Cooperative Oncology Group performance status (ECOG PS) score, HGB, and EB virus DNA were independent influencing factors for the prognosis of ENKTL patients (P<0.05). In this study, the predictive performance of the prognostic factors is superior to the international prognostic index, Korean prognostic index, and prognostic index of natural killer lymphoma. Conclusion: Gender, CA stage, ECOG PS score, HGB, and EB virus DNA are prognostic factors for ENKTL patients treated with pegaspargase/L-asparaginase.

The Dynamics of Dopamine D2 Receptor-Expressing Striatal Neurons and the Downstream Circuit Underlying L-Dopa-Induced Dyskinesia in Rats / 神经科学通报·英文版

L-dopa (l-3,4-dihydroxyphenylalanine)-induced dyskinesia (LID) is a debilitating complication of dopamine replacement therapy for Parkinson's disease. The potential contribution of striatal D2 receptor (D2R)-positive neurons and downstream circuits in the pathophysiology of LID remains unclear. In this study, we investigated the role of striatal D2R+ neurons and downstream globus pallidus externa (GPe) neurons in a rat model of LID. Intrastriatal administration of raclopride, a D2R antagonist, significantly inhibited dyskinetic behavior, while intrastriatal administration of pramipexole, a D2-like receptor agonist, yielded aggravation of dyskinesia in LID rats. Fiber photometry revealed the overinhibition of striatal D2R+ neurons and hyperactivity of downstream GPe neurons during the dyskinetic phase of LID rats. In contrast, the striatal D2R+ neurons showed intermittent synchronized overactivity in the decay phase of dyskinesia. Consistent with the above findings, optogenetic activation of striatal D2R+ neurons or their projections in the GPe was adequate to suppress most of the dyskinetic behaviors of LID rats. Our data demonstrate that the aberrant activity of striatal D2R+ neurons and downstream GPe neurons is a decisive mechanism mediating dyskinetic symptoms in LID rats.

Clinicopathological Features and Prognosis of Patients Newly Diagnosed With Lung Adenocarcinoma With Both EGFR Mutation and C-MET Amplification / 中国医学科学院学报

Objective To explore the clinicopathological features and prognosis of the patients newly diagnosed with lung adenocarcinoma with both EGFR mutation and C-MET amplification.Methods The pathological sections were reviewed.EGFR mutation was detected by amplification refractory mutation system-quantitative real-time polymerase chain reaction,and C-MET amplification by fluorescence in situ hybridization.The clinicopathological features and survival data of the patients newly diagnosed with lung adenocarcinoma with both EGFR mutation and C-MET amplification were analyzed retrospectively.Results In 11 cases of EGFR mutation combined with C-MET amplification,complex glands and solid high-grade components were observed under a microscope in 10 cases except for one case with a cell block,the tissue structure of which was difficult to be evaluated.The incidence of lung adenocarcinoma in the patients with EGFR mutation combined with C-MET amplification at clinical stage Ⅳ was higher than that in the EGFR mutation or C-MET amplification group (all P<0.001),whereas the difference was not statistically significant between the EGFR mutation group and C-MET amplification group at each clinical stage (all P>0.05).There was no significant difference in the trend of survival rate between EGFR gene group and C-MET amplification group (χ2=0.042,P=0.838),while the survival of the patients with EGFR mutation combined with C-MET amplification was worse than that of the patients with EGFR mutation (χ2=246.72,P<0.001) or C-MET amplification (χ2=236.41,P<0.001).Conclusions The patients newly diagnosed with lung adenocarcinoma with EGFR mutation plus C-MET amplification demonstrate poor histological differentiation,rapid progress,and poor prognosis.The patients are often in the advanced stage when being diagnosed with cancer.Attention should be paid to this concurrent adverse driving molecular event in clinical work.With increasing availability,the inhibitors targeting C-MET may serve as an option to benefit these patients in the near future.

Impaired cognitive map in transgenic animals relevant to Alzheimer's disease: from neurons to network / 生理学报

Alzheimer's disease (AD) is a typical cognitive disorder with an increasing incidence in recent years. AD is also one of the main causes of disability and death of the elderly in current aging society. One of the most common symptoms of AD is spatial memory impairment, which occurs in more than 60% of patients. This memory loss is closely related to the impairment of cognitive maps in the brain. The entorhinal grid cells and the hippocampal place cells are important cellular basis for spatial memory and navigation functions in the brain. Understanding the abnormal firing pattern of these neurons and their impaired coordination to neural oscillations in transgenic rodents is crucial for identifying the therapeutic targets for AD. In this article, we review recent studies on neural activity based on transgenic rodent models of AD, with a focus on the changes in the firing characteristics of neurons and the abnormal electroencephalogram (EEG) rhythm in the entorhinal cortex and hippocampus. We also discuss potential cell-network mechanism of spatial memory disorders caused by AD, so as to provide a scientific basis for the diagnosis and treatment of AD in the future.

Tiaoshen acupuncture for primary insomnia: a pilot randomized controlled trial / 中国针灸

OBJECTIVE@#To observe the effects of Tiaoshen (regulating the spirit) acupuncture on cognitive function and sleep quality in patients with primary insomnia (PI).@*METHODS@#Sixty patients with PI were randomly divided into an observation group (30 cases, 2 cases dropped off) and a control group (30 cases, 2 cases dropped off, 1 case was excluded). The patients in the observation group were treated with acupuncture at Baihui (GV 20), Shenting (GV 24), Sishencong (EX-HN 1), and bilateral Benshen (GB 13), Shenmen (HT 7), Neiguan (PC 6), Sanyinjiao (SP 6). The patients in the control group were treated with shallow needling at non-effective points. Each treatment was provided for 30 min, once every other day, 3 treatments per week for 4 weeks. The Montreal cognitive assessment (MoCA), digit span test (DST), trail making test (TMT)-A, Pittsburgh sleep quality index (PSQI), and fatigue scale-14 (FS-14) were used to assess cognitive function and sleep quality before and after treatment, as well as in follow-up of 4-week after treatment completion. Correlation analysis was conducted between the differences in PSQI scores and differences in MoCA scores before and after treatment in the observation group.@*RESULTS@#Compared with before treatment, the total score, visuospatial and executive function score and delayed memory score of MoCA as well as DST backward score were increased (P<0.01), while TMT-A time, PSQI and FS-14 scores were significantly reduced (P<0.01) after treatment and in follow-up in the observation group. Compared with before treatment, the PSQI score in the control group was reduced (P<0.01, P<0.05). After treatment and in follow-up, the observation group had significantly higher total score, visuospatial and executive function score, delayed memory score of MoCA, and DST backward score compared to the control group (P<0.05, P<0.01). In the observation group, the TMT-A time was significantly shorter than that in the control group (P<0.05, P<0.01), and the PSQI and FS-14 scores were significantly lower than those in the control group (P<0.01). In the observation group, there was a negative correlation between the difference in PSQI scores (post-treatment minus pre-treatment) and the difference in MoCA scores (post-treatment minus pre-treatment) (r=-0.481, P<0.01). A similar negative correlation was found between the difference in PSQI scores (follow-up minus pre-treatment) and the difference in MoCA scores (follow-up minus pre-treatment) (r=-0.282, P<0.05).@*CONCLUSION@#Tiaoshen acupuncture could improve cognitive function, enhance sleep quality, and alleviate daytime fatigue in patients with PI. The improvement in cognitive function in patients with PI is correlated with the improvement in sleep quality.

Secretory expression of human thyroid stimulating hormone receptor A subunit in sf9 insect cell system / 西安交通大学学报(医学版)

【Objective】 To construct the secretory expression system of insect cells to express the secretory TSHR A subunit protein in the ovarian cells of Spotoma oryzae (sf9). 【Methods】 A recombinant plasmid containing the target protein was constructed, and then the positive bacmid was screened out by the blue and white spots experiment. The verified bacmid was transfected into SF9 insect cells to obtain recombinant baculovirus. The virus was amplified, and the titer level was detected by virus plaque assay. Finally, Western blotting was used to identify the expression of the recombinant protein and optimize the expression conditions. 【Results】 During the construction of the protein expression system, PCR identification and sequencing results confirmed the correctness of the sequences of the recombinant plasmid and the recombinant bacmid. After the transfection of the bacmid, the signs of virus budding were observed in sf9 cells. The virus was collected and amplified. The titer of P1 generation virus was 2×107 pfu/m according to the plaque assay. The recombinant protein was identified by Western blotting and confirmed to be exogenous into the culture medium. The optimal condition for virus infection and protein expression was 72 h after the infection when the multiplicity of infection (MOI) was 1. 【Conclusion】 We constructed an insect cell expression system secreting TSHR 22-289 (55 ku), and the protein could be successfully glycolyzed. This system provides a preliminary basis for the construction and production of its industrial platform and also provides a useful tool for studies on TSHR protein and prevention of GO in the future.

Improvement effect of diterpene ginkgolides on acute tMCAO rats and chronic tMCAO rats / 药学学报

To study the cognitive effects of diterpene ginkgolides (DG), transient middle cerebral artery occlusion (tMCAO)-induced rats were established. tMCAO-rats induced by suture method were divided into sham operation group, solvent control group, NBP group, DG group. The animal experiments in the present study were performed in accordance with the Ethical Guidelines of the Laboratory Animal Welfare Ethical Committee of Peking Union Medical College (00000646, 00000635). The effects of DG on tMCAO rats were evaluated by neurological severity score, cerebral infarction volume measurement, step-down and Morris water maze test. In the acute tMCAO rat model, 100 mg·kg-1 DG improved the neural score and infarction volume. In the chronic tMCAO rat model, DG 100 mg·kg-1 significantly improved the survival rate of tMCAO-induced rats. The Morris water maze results showed 100 mg·kg-1 DG decreased the latency of tMCAO-induced rats to find the platform, while the effect was weaker than the NBP. However, DG 30 mg·kg-1 did not show a significant effect. In conclusion, DG exerted a therapeutic effect on transient middle cerebral artery occlusion.

The PK bioanalysis method study of c-Met antibody-drug conjugate (RC108) in cynomolgus monkey / 药学学报

Antibody-drug conjugate (ADC) has the characteristics of low toxicity and high efficiency, and plays an important role in cancer treatment. However, due to the complexity of its structure, it brings difficulties in pharmacokinetic (PK) bioanalysis. This study established an analytical method for the detection of ADC (RC108) in cynomolgus monkey plasma by ligand-binding assay (LBA) and liquid chromatography tandem mass spectrometry (LC-MS/MS), which was used to analyze and quantify the total antibody, bound antibody and free drug in cynomolgus monkey plasma. Based on the LBA method, rabbit anti-RC108 Fab and mouse anti-MMAE (monomethyl auristatin E) mAb were pre-coated in 96-well plates as the total antibody and antibody binding reagents, respectively. The samples to be tested were added, and then the detection reagents were added in turn. Goat anti-human IgG (H+L)-HRP, chromogenic solution tetramethylbenzidine (TMB), H2SO4 terminate the reaction, read data at 450 nm/630 nm wavelength of microplate reader; LC-MS/MS analysis method quantifies MMAE concentration, and refer to relevant regulations for methodological validation. The analytical method for quantifying total antibody, bound antibody and free drug of RC108 drug obtained good accuracy and precision, and the selectivity, dilution linearity, hook effect, parallelism and stability were verified. Meet the requirements of biological analysis. Finally, a bioanalytical method for the determination of the concentration of the test substance RC108 (total antibody, conjugated antibody, free MMAE) in cynomolgus monkey plasma with high sensitivity and high throughput was established by LBA and LC-MS/MS method. Subsequent non-clinical research on PK research in cynomolgus monkeys will provide technical support.

Observation of tear film stability in dry eye patients with different lipid layer thickness / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To explore the difference of tear film stability among different lipid layer thickness.METHOD: A total of 194 dry eye patients(384 eyes)admitted to our hospital from June 2020 to December 2021 were enrolled in this study. The tear meniscus height, the first tear film break-up time and lipid layer thickness were measured by corneal topographer. The tear meniscus height and the first tear film break-up time among different lipid layer thickness were compared and the correlation between them was analyzed.RESULTS: The included patients(384 eyes)were divided into lipid rich group(49 eyes), lipid balance group(27 eyes), slight lipid deficiency group(266 eyes)and significant lipid deficiency group(42 eyes)according to the lipid layer thickness. The differences of the tear meniscus height were statistically different(P=0.022), while the differences of the first tear film break-up time were not statistically different(P=0.322). The lipid layer thickness was positively correlated with tear meniscus height(rs=0.143, P=0.006). There was no correlation between lipid layer thickness and the first tear film break-up time(rs=-0.090, P=0.083), nor was there correlation between tear meniscus height and the first tear film break-up time(rs=0.038, P=0.460).CONCLUSION: There was no significant difference in tear film stability in dry eye patients with different lipid layer thickness.

Multicenter Prospective Study of Different Induction Regimens of Azacytidine in Treatment of Elderly Patients with Acute Myeloid Leukemia / 中国实验血液学杂志

OBJECTIVE@#To observe the efficacy and safety of different induction regimens of same total dosage of azacitidine (Aza), including standard dose (standard dose group) and low-dose long-term (adjusted dose group), in the treatment of elderly acute myeloid leukemia (AML).@*METHODS@#A total of 103 elderly patients with AML (non-acute promyelocytic leukemia) from January 2020 to June 2021 were enrolled. Aza was administered at the standard dose of 75 mg/(m2·d) for 7 days in the standard dose group (50 cases), while at 100 mg/d for 7-12 days in the adjusted dose group (53 cases). The administration days in adjusted dose group was calculated based on the total standard dose of the patient's single course of treatment. The efficacy and safety between standard dose group and adjusted dose group were compared. Subgroup analysis were performed in the two groups for Aza alone, Aza combined with BCL-2 inhibitor, and Aza combined with low-dose chemotherapy for efficacy and safety.@*RESULTS@#There were no significant differences in overall response rate (ORR), incidence of adverse reaction, and 1-year overall survival (OS) rate between standard dose group and adjusted dose group (P >0.05). The ORR of combination was higher than that of Aza alone (P < 0.05), while there was no significant difference in ORR between Aza combined with BCL-2 inhibitor and Aza combined with low-dose chemotherapy (P >0.05). The combination of BCL-2 inhibitor did not increase the incidence of adverse reactions compared wtih Aza alone. There was a higher risk of myelosuppression and pulmonary infection with a combination of low-dose chemotherapy than with a combination of BCL-2 inhibitor and Aza alone (P <0.05). No significant difference was observed in 1-year OS between Aza alone, Aza combined with BCL-2 inhibitor, and Aza combined with low-dose chemotherapy (P >0.05).@*CONCLUSIONS@#Both two induction regimens can be used in elderly AML patients who cannot tolerate intensive chemotherapy with similar overall effectiveness and safety. Aza combined with low-dose chemotherapy may result in increased ORR and an increased incidence of serious adverse reactions, and may not result in longer survival compared with Aza alone. Aza combined with BCL-2 inhibitor not only has similar effect in complete remission, objective response rate, and OS compared with Aza combined with low-dose chemotherapy, but also has higher safety.

Determination of plasma protein binding rate of Shuganning Injection using equilibrium dialysis and UPLC-MS/MS / 中国中药杂志

Traditional Chinese medicine(TCM) compound preparations have complex compositions. As a widely used TCM injection, Shuganning Injection, its in vivo processes are not yet fully understood. Determining the plasma protein binding rate is of great significance for pharmacokinetic and pharmacodynamic studies. In this experiment, the equilibrium dialysis method combined with UPLC-MS/MS technology was used to determine the plasma protein binding rates of 10 components, including p-hydroxyacetophenone, caffeic acid, baicalein, oroxylin A, geniposide, baicalin, cynaroside, oroxylin A-7-O-β-D-glucuronide, scutellarin, and hyperoside, in Shuganning Injection in rat and human plasma to provide a theoretical basis for further elucidating the in vivo processes of Shuganning Injection and guiding clinical medication. The results showed that, except for baicalein and geniposide, the plasma protein binding rates of the other eight components were higher in human plasma than in rat plasma, and there were interspecies differences. In human plasma, except for geniposide, caffeic acid, and baicalin, the plasma protein binding rates of the remaining seven components were above 80%, with baicalein and oroxylin A exceeding 90%. All components exhibit a high level of binding to plasma proteins, with the exception of geniposide.

Preparation of vitexin albumin nanoparticles and its pharmacokinetic study / 中国中药杂志

This study aims to prepare vitexin albumin nanoparticles(VT-BSA-NPs) to alleviate the low bioavailability of vitexin(VT) in vivo due to its poor water solubility. VT micro powders were prepared by the antisolvent crystallization method, and the morphology, size, and physicochemical properties of VT micro powders were studied. The results showed that the VT micro powder had a particle size of(187.13±7.15) nm, an approximate spherical morphology, and a uniform size distribution. Compared with VT, the chemical structure of VT micro powders has not changed. VT-BSA-NPs were prepared from VT micro powders by desolvation-crosslinking curing method. The preparation process was screened by single factor test and orthogonal test, and the quality evaluation of the optimal prescription particle size, PDI, Zeta potential, EE, and morphology was performed. The results showed that the average particle size of VT-BSA-NPs was(124.33±0.47) nm; the PDI was 0.184±0.012; the Zeta potential was(-48.83±2.20) mV, and the encapsulation rate was 83.43%±0.39%, all of which met the formulation-related requirements. The morphological results showed that the VT-BSA-NPs were approximately spherical in appearance, regular in shape, and without adhesion on the surface. In vitro release results showed a significantly reduced release rate of VT-BSA-NPs compared with VT, indicating a good sustained release effect. LC-MS/MS was used to establish an analytical method for in vivo analysis of VT and study the plasma pharmacokinetics of VT-BSA-NPs in rats. The results showed that the specificity of the analytical method was good, and the extraction recovery was more than 90%. Compared with VT and VT micro powders, VT-BSA-NPs could significantly increase AUC, MRT, and t_(1/2), which was beneficial to improve the bioavailability of VT.

Progress of ibrutinib combined with CD19 chimeric antigen receptor T-cell in treatment of chronic lymphocytic leukemia / 白血病·淋巴瘤

Chronic lymphocytic leukemia (CLL) is a clonal malignant disease of B lymphocytes (T lymphocytes are rare) and usually occurs in elderly people. CLL has a highly variable clinical course, with a median survival of 35 to 63 months. In the era of immunochemotherapy, the survival of CLL patients has improved significantly, but most patients still have primary drug resistance and relapse after the treatment. The emergence of Bruton tyrosine kinase inhibitor has completely changed the treatment mode of CLL, making the treatment of CLL into the era of targeted therapy. Ibrutinib combined with CD19 chimeric antigen receptor T-cell has good efficacy and can improve the prognosis of patients.

Effects of PEEK Anisotropy Formed by 3D Printing on Mechanical Properties of Femoral Substitutes / 医用生物力学

Objective Aiming at the problem of significant anisotropy in the three-dimensional ( 3D) printed polyether-ether-ketone ( PEEK) bone substitutes manufactured by material extrusion technology, taking the femur, the main load-bearing long bone of the lower limb, as an example, the biomechanical properties of the femoral model under different direction in the build chamber were evaluated by the combination of finite element analysis and in-vitro mechanical experiment. Methods A left femoral model was obtained by reconstruction from CT data. The stress and displacement of the 3D printed PEEK femur with different directions in the build chamber under five physiological postures in the human gait cycle were simulated by varying the orthogonal anisotropy mechanical properties. An in-vitro mechanical experiment was conducted to investigate the safety and stability of the femur through a 3D printed PEEK femur. Results When the long axis of the femur model was perpendicular to the building platform of the 3D printer, a better mechanical property was obtained, and the maximum von Mises stress was 46. 56 MPa, which was lower than the yield stress of PEEK, while the maximum displacement was larger than that of the natural femur under same loading condition. Therefore, the 3D printed PEEK femur met the strength requirement, but the stability needs to be improved. Conclusions The long axis is recommended to be perpendicular to the building platform when the material extrusion technology was used for the substitute of the load-bearing long bone, and the effect of its anisotropy on service performance of the substitute should be carefully considered when the 3D printing technology is used for load-bearing bone substitute.

Protective effect of breviscapine against brain injury induced by intrauterine inflammation in preterm rats and its mechanism / 中国当代儿科杂志

OBJECTIVES@#To study the protective effect of breviscapine against brain injury induced by intrauterine inflammation in preterm rats and its mechanism.@*METHODS@#A preterm rat model of brain injury caused by intrauterine inflammation was prepared by intraperitoneal injections of lipopolysaccharide in pregnant rats. The pregnant rats and preterm rats were respectively randomly divided into 5 groups: control, model, low-dose breviscapine (45 mg/kg), high-dose breviscapine (90 mg/kg), and high-dose breviscapine (90 mg/kg)+ML385 [a nuclear factor erythroid 2-related factor 2 (Nrf2) inhibitor, 30 mg/kg] (n=10 each). The number and body weight of the live offspring rats were measured for each group. Hematoxylin-eosin staining was used to observe the pathological morphology of the uterus and placenta of pregnant rats and the pathological morphology of the brain tissue of offspring rats. Immunofluorescent staining was used to measure the co-expression of ionized calcium binding adaptor molecule-1 (IBA-1) and nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) in the cerebral cortex of offspring rats. ELISA was used to measure the levels of interleukin-6 (IL-6), interleukin-8 (IL-8), and interleukin-1β (IL-1β) in the brain tissue of offspring rats. Western blotting was used to measure the expression of Nrf2 pathway-related proteins in the brain tissue of offspring rats.@*RESULTS@#Pathological injury was found in the uterus, and placenta tissue of the pregnant rats and the brain tissue of the offspring rats, and severe microglia pyroptosis occurred in the cerebral cortex of the offspring rats in the model group. Compared with the control group, the model group had significant reductions in the number and body weight of the live offspring rats and the protein expression levels of Nrf2 and heme oxygenase-1 (HO-1) in the brain tissue of the offspring rats (P<0.05), but significant increases in the relative fluorescence intensity of the co-expression of IBA-1 and NLRP3, the levels of the inflammatory factors IL-6, IL-8, and IL-1β, and the protein expression levels of NLRP3 and caspase-1 in the brain tissue of the offspring rats (P<0.05). Compared with the model group, the breviscapine administration groups showed alleviated pathological injury of the uterus and placenta tissue of the pregnant rats and the brain tissue of the offspring rats, significant increases in the number and body weight of the live offspring rats and the protein expression levels of Nrf2 and HO-1 in the brain tissue of the offspring rats (P<0.05), and significant reductions in the relative fluorescence intensity of the co-expression of IBA-1 and NLRP3, the levels of the inflammatory factors IL-6, IL-8, and IL-1β, and the protein expression levels of NLRP3 and caspase-1 in the brain tissue of the offspring rats (P<0.05). The high-dose breviscapine group had a significantly better effect than the low-dose breviscapine (P<0.05). ML385 significantly inhibited the intervention effect of high-dose breviscapine (P<0.05).@*CONCLUSIONS@#Breviscapine can inhibit inflammatory response in brain tissue of preterm rats caused by intrauterine inflammation by activating the Nrf2 pathway, and it can also inhibit microglial pyroptosis and alleviate brain injury.

Homeostatic medicine: new strategy and concept of health maintenance as well as diagnosis and treatment of diseases / 中华口腔医学杂志

Homeostasis is a dynamic balance process of self-regulating. Biological systems remain stable through adapting to changing external conditions to maintain normal life activities. Homeostatic medicine is the science of studying homeostasis of human molecules, cells, organs and the whole body. It is a comprehensive discipline based on maintaining homeostasis to keep human health and assist for diseases prevention and diagnoses. Homeostatic medicine focuses on the whole body and on the role of homeostasis in health and disease, which is expected to provide new ideas and strategies for maintaining health as well as diagnosing and treating diseases. Nitric oxide (NO) plays an important role in the control of multisystem homeostasis. Nitrate is an important substance in regulating NO homeostasis through the nitrate-nitrite-NO pathway. Sialin, nitrate transporter which is located in the cell membrane and cytoplasm, mediates multiple cellular biological functions. The nitrate-nitrite-NO pathway and sialin-mediated biological functions play an important role in the regulation of body homeostasis.