[Objective] To evaluate the feasibility of a novel outpatient infusion model for blinatumomab in two acute lymphoblastic leukemia (ALL) patients, aiming to address challenges of poor treatment tolerance, high healthcare costs, and compromised quality of life, thereby providing clinical insights for broader adoption of this approach. [Methods] Two post-allogeneic hematopoietic stem cell transplantation (allo-HSCT) patients undergoing blinatumomab maintenance therapy were selected to evaluate the efficacy of the outpatient infusion model. Patient selection criteria, nursing protocols, standardized workflows, and advancements in infusion practices were systematically analyzed combined with a review of global developments in this field. [Results] Both patients completed outpatient blinatumomab infusion without severe adverse events, demonstrating preliminary feasibility and safety of this model. The novel approach enhanced treatment convenience, reduced hospitalization costs, and improved quality of life. [Conclusion] Despite the limited sample size, this pilot study highlights the potential of outpatient blinatumomab administration as a viable alternative to traditional inpatient regimens.

Aim To explore how Danzhi Jiangtang cap-sules(DJC)safeguard the mitochondrial activity of vascular smooth muscle cells(VSMCs)by controlling the LncRNA TUG1/β-catenin signaling pathway to de-crease vascular calcification(VC).Methods Vascu-lar smooth muscle cell calcification models were in-duced with β-glycerin and diabetic vascular calcifica-tion rat models were induced with vitamin D3+high-fat diet.Von Kossa staining was applied to detect cal-cification of cells and vascular tissue.Colorimetric method of phthalein complex was used to determine calcium content.P-nitrobenzene phosphate colorimetry was employed to assess alkaline phosphatase(ALP)activity.RT-qPCR was used to analyze the expression of VSMCs'osteoblast transformation related genes bone morphogenetic protein2(BMP2),smooth muscle actin alpha(α-SMA),taurine up-regulated1,LncRNA Tug1(Lnc-RNA TUG1),and β-catenin.Western blotting was utilized to detect the protein expression of BMP2,α-SMA and β-catenin.The mitochondrial membrane potential was detected by JC-1 fluorescence probe.Mitochondrial structure was observed by trans-mission electron microscope.Results DJC reduced LncRNA TUG1 expression,down-regulated β-catenin expression,decreased ALP activity and calcium depo-sition,protected mitochondrial function,restored mem-brane potential,and decreased osteoblastic transforma-tion of VSMCs induced by glycerin phosphate.Impor-tantly,DJC attenuated diabetic lower limb VC by down-regulating the expression of LncRNA TUG1,β-catenin,and elevating the expression of α-SMA.Con-clusions DJC capsules significantly improved VSMCs by protecting mitochondrial function by LncRNA TUG1/β-catenin signaling to reduce VSMCs'osteo-blast transformation.

Aim To investigate the effect of quercetin on the aging model of bone marrow mesenchymal stem cells established under microgravity. Methods Using 3D gyroscope, a aging model of bone marrow mesenchymal stem cells was constructed, and after receiving quercetin and microgravity treatment, the anti-aging effect of the quercetin was evaluated by detecting related proteins and oxidation indexes. Results Compared to the control group, the expressions of age-related proteins p21, pi6, p53 and RB in the microgravity group significantly increased, while the expressions of cyclin D1 and lamin B1 significantly decreased, with statistical significance (P<0.05). In the microgravity group, mitochondrial membrane potential significantly decreased (P<0.05), ROS accumulation significantly increased (P <0.05), SOD content significantly decreased and MDA content significantly increased (P<0.05). Compared to the microgravity group, the expressions of age-related proteins p21, pi6, p53 and RB in the quercetin group significantly decreased, while the expressions of cyclin D1 and lamin B1 significantly increased, with statistical significance (P<0.05). In the quercetin group, mitochondrial membrane potential significantly increased (P<0.05), ROS accumulation significantly decreased (P<0.05), SOD content significantly increased and MDA content significantly decreased (P<0.05). Conclusions Quercetin can resist oxidation, protect mitochondrial function and normal cell cycle, thus delaying the aging of bone marrow mesenchymal stem cells induced by microgravity.

Objective To study the microscopic structure and morphological characteristics of Zebrafish eyeball and retina at different developmental stages, and to lay a foundation for visual research model. Methods Select eight groups of zebrafish at different ages, with six fish in each group, 48 fish in total. Optical microscopy and transmission electron microscopy were used to observe the eyeball structure of Zebrafish at different developmental stages, and the thickness of retinal each layer was measured to analyze the temporal and spatial development pattern. The morphological characteristics of various cells in the retina and the way of nerve connection were observed from the microscopic and ultrastructural aspects, especially the structural differences between rod cells and cone cells. Results The retina of Zebrafish can be divided into ten layers including retinal pigment epithelial layer, rod cells and cone cells layer, outer limiting membrane, outer nuclear layer, outer plexiform layer, inner nuclear layer, inner plexiform layer, ganglion cell layer, nerve fiber layer, inner limiting membrane. Rod cells had a smaller nucleus and a higher electron density than cone cells. Photoreceptor terminals were neatly arranged in the outer plexiform layer, forming neural connections with horizontal cells and bipolar cells, and several synaptic ribbons are clearly visible within them. In Zebrafish retina, ganglion cell layer and inner plexiform layer are the earliest developed. With the growth and development of Zebrafish, the thickness of rod cells and cone cells layer and retinal pigment epithelial layer gradually increases, and the retinal structure was basically developed in about 10 weeks. Conclusion The retinal structure of Zebrafish is typical, with obvious stratification and highly differentiated nerve cells. There are abundant neural connections in the outer plexiform layer. The ocular development characteristics of Zebrafish are similar to those of most mammals.

OBJECTIVE: To investigate whether electroacupuncture (EA) at sensitized acupoints could reduce sympathetic-sensory coupling (SSC) and neurogenic inflammatory response by interfering with 5-hydroxytryptamine (5-HT)ergic neural pathways to relieve colitis and somatic referred pain, and explore the underlying mechanisms. METHODS: Rats were treated with 5% dextran sodium sulfate (DSS) solution for 7 days to establish a colitis model. Twelve rats were randomly divided into the control and model groups according to a random number table (n=6). According to the "Research on Rat Acupoint Atlas", sensitized acupoints and non-sensitized acupoints were determined. Rats were randomly divided into the control, model, Zusanli-EA (ST 36), Dachangshu-EA (BL 25), and Xinshu (BL 15) groups (n=6), as well as the control, model, EA, and EA + GR113808 (a 5-HT inhibitor) groups (n=6). The rats in the control group received no treatment. Acupuncture was administered on 2 days after modeling using the stimulation pavameters: 1 mA, 2 Hz, for 30 min, with sparse and dense waves, for 14 consecutive days. GR113808 was injected into the tail vein at 5 mg/kg before EA for 10 min for 7 consecutive days. Mechanical sensitivity was assessed with von Frey filaments. Body weight and disease activity index (DAI) scores of rats were determined. Hematoxylin and eosin staining was performed to observe colon histopathology. SSC was analyzed by immunofluorescence staining. Immunohistochemical staining was performed to detect 5-HT and substance P (SP) expressions. The calcitonin gene-related peptide (CGRP) in skin tissue and tyrosine hydroxylase (TH) protein levels in DRG were detected by Western blot. The levels of hyaluronic acid (HA), bradykinin (BK), prostaglandin I2 (PGI2) in skin tissue, 5-HT, tryptophan hydroxylase 1 (TPH1), serotonin transporters (SERT), 5-HT 3 receptor (5-HT3R), and 5-HT 4 receptor (5-HT4R) in colon tissue were measured by enzyme-linked immunosorbent assay (ELISA). RESULTS: BL 25 and ST 36 acupoints were determined as sensitized acupoints, and BL 15 acupoint was used as a non-sensitized acupoint. EA at sensitized acupoints improved the DAI score, increased mechanical withdrawal thresholds, and alleviated colonic pathological damage of rats. EA at sensitized acupoints reduced SSC structures and decreased TH and CGRP expression levels (P<0.05). Furthermore, EA at sensitized acupoints reduced BK, PGI2, 5-HT, 5-HT3R and TPH1 levels, and increased HA, 5-HT4R and SERT levels in colitis rats (P<0.05). GR113808 treatment diminished the protective effect of EA at sensitized acupoints in colitis rats (P<0.05). CONCLUSION EA at sensitized acupoints alleviated DSS-induced somatic referred pain in colitis rats by interfering with 5-HTergic neural pathway, and reducing SSC inflammatory response.
Rats ; Animals ; Electroacupuncture ; Rats, Sprague-Dawley ; Serotonin ; Acupuncture Points ; Pain, Referred ; Calcitonin Gene-Related Peptide ; Signal Transduction ; Colitis/therapy* ; Indoles ; Sulfonamides

Objective To compare the effects of 20 mg qd and 10 mg bidadministration of iprrazole enteric-coated tablets on the control of gastric acid in healthy subjects.Methods A randomized,single-center,parallel controlled trial was designed to include 8 healthy subjects.Randomly divided into 2 groups,20 mg qd administration group:20 mg enteric-coated tablets of iprrazole in the morning;10 mg bid administration group:10 mg enteric-coated tablets of iprrazole in the morning and 10 mg in the evening.The pH values in the stomach of the subjects before and 24 h after administration were monitored by pH meter.The plasma concentration of iprazole after administration was determined by HPLC-MS/MS.The main pharmacokinetic parameters were calculated by Phoenix WinNonlin(V8.0)software.Results The PK parameters of iprrazole enteric-coated tablets and reference preparations in fasting group were as follows:The Cmax of 20 mg qd group and 10 mg bid group were(595.75±131.15)and(283.50±96.98)ng·mL-1;AUC0-t were(5 531.94±784.35)and(4 686.67±898.23)h·ng·mL-1;AUC0-∞ were(6 003.19±538.59)and(7 361.48±1 816.77)h·ng·mL-1,respectively.The mean time percentage of gastric pH＞3 after 20 mg qd and 10 mg bid were 82.64％and 61.92％,and the median gastric pH within 24 h were 6.25±1.49 and 3.53±2.05,respectively.The mean gastric pH values within 24 h were 5.71±1.36 and 4.23±1.45,respectively.The correlation analysis of pharmacokinetic/pharmacodynamics showed that there was no significant correlation between the peak concentration of drug in plasma and the inhibitory effect of acid.Conclusion Compared with the 20 mg qd group and the 10 mg bid group,the acid inhibition effect is better,the administration times are less,and the safety of the two administration regimes is good.

Mutations in myosin heavy chain 7(MYH7)and myosin binding protein C3(MYBPC3)genes encoding thick filaments are the main cause of hypertrophic cardiomyopathy(HCM),while a small part of HCM is caused by mutations of troponin C1,slow skeletal and cardiac type(TNNC1),troponin T2,cardiac type(TNNT2),troponin I3,cardiac type(TNNI3),actin alpha cardiac muscle 1(ACTC1),and tropomyosin 1(TPM1)genes encoding thin filaments.In this review,we mainly introduce the detailed mechanism and research status of HCM caused by mutations of the gene encoding cardiomyocyte sarcomere in the past few years,in order to provide reference for further study of the pathogenesis and treatment of HCM.

ObjectiveAngle-closure glaucoma (ACG) is one of the major eye-blinding diseases. To diagnose ACG, it is crucial to examine the anterior chamber angle. Current diagnostic tools include slit lamp gonioscopy, water gonioscopy, ultrasound biomicroscopy (UBM), and anterior segment optical coherence tomography (AS-OCT). Slit lamp and water gonioscopy allow convenient observation of the anterior chamber angle, but pose risks of invasive operation and eye infections. UBM can accurately measure the structure of the anterior chamber angle. However, it is complex to operate and unsuitable for patients, who have undergone trauma or ocular surgery. Although AS-OCT provides detailed images, it is costly. The aim of this study is to explore a non-invasive, non-destructive optical reflection tomography (ORT) technique. This technique can achieve low-cost three-dimensional imaging and full-field anterior chamber angle measurement of the porcine eye. MethodsThe experiment involved assembling an optical reflection tomography system, which included a complementary metal oxide semiconductor (CMOS) camera, a telecentric system, a stepper motor, and a white light source, achieving a spatial resolution of approximately 8.5 μm. The process required positioning the porcine eye at the center of the field of the imaging system and rotating it around its central axis using a stepper motor. Reflection projection images were captured at each angle with an exposure time of 1.0 ms and an interval of 2°. The collected reflection-projection data were processed using a filtered reflection tomography algorithm, generating a series of two-dimensional slice data. These slices essentially represented cross-sectional views of the three-dimensional structural image, and were reconstructed into a complete three-dimensional structural image. Based on the reconstructed three-dimensional structural image of the porcine eye, the anterior chamber angles at different positions were measured, and a distribution map of these angles was drawn. Simultaneously, the ORT measurements were compared with the standard results obtained from optical coherence tomography (OCT) to assess the accuracy of ORT measurements. ResultsIn this study, we successfully obtained the reflection projection data of a porcine eye using ORT technology, reconstructed its three-dimensional structural image, and measured the anterior chamber angle, generating the corresponding distribution map. To better distinguish the different structural parts of porcine eye, the three-dimensional structural image was marked with blue, green, and yellow dashed lines from the outer to the inner layers. The area between the blue and green dashed lines corresponded to the sclera. The area between the green and yellow dashed lines corresponded to the iris. The area inside the yellow dashed line corresponded to the pupil. The three-dimensional structural image clearly revealed the key anatomical features of the porcine eye. It was able to measure the anterior chamber angle at different positions. Additionally, the anterior chamber angle measurements of the porcine eye using ORT were compared with the measurements obtained using a TEL320C1 type OCT system, showing an average deviation of 0.51° and a mean square error MSE of 0.317. ConclusionORT is a non-invasive, non-destructive, low-cost, and high-resolution imaging technique capable of achieving three-dimensional structural imaging and full-field anterior chamber angle measurement of a porcine eye. This technology offers a new perspective for the diagnosis of angle-closure glaucoma and is significant for the screening, diagnosis, and monitoring of eye diseases, potentially benefiting clinics and small hospitals in remote areas in the future.

Lipopolysaccharides (LPS) are major outer membrane components of Gram-negative bacteria. Unlike most Gram-negative bacteria, Acinetobacter baumannii can still survive and acquire polymyxin resistance after complete loss of LPS. Previous studies of LPS-deficient Acinetobacter baumannii mostly focused on LPS-deficient strains induced by polymyxin, whose background was complex and unstable. To investigate LPS loss-mediated polymyxin resistant-Acinetobacter baumannii, this study constructed a stable and clear background LPS-deficient strain by knocking out lpxC gene in Acinetobacter baumannii ATCC 19606 with CIRSPR/Cas9, and then studied the phenotypic changes of the lpxC-deficient strain including morphology, growth rate, antibiotic susceptibility, virulence, membrane permeability, and membrane potential. Animal experiments were approved by the Animal Care and Welfare Committee Institute of Medicinal Biotechnology, CAMS and PUMC (approval number: IMB-20240119D₉). The results indicated that the lpxC gene of Acinetobacter baumannii ATCC 19606 was successfully knocked out. After losing the lpxC, the strain underwent the morphological change from rod-shaped to spherical. Furthermore, it leads to reduced growth rate, enhanced membrane permeability, decreased membrane potential, lower virulence, and increased antibiotic susceptibility to β-lactams, quinolones, aminoglycosides, macrolides, glycopeptides. The lpxC deletion results in significant changes in membrane homeostasis and adaptability of Acinetobacter baumannii. Understanding the phenotypic changes of colistin-resistant Acinetobacter baumannii mediated by LPS loss is useful for exploring the resistance mechanism of Acinetobacter baumannii and developing new therapeutic strategies.

Objective To elucidate the potential mechanisms by which mesothelin(MSLN)contributes to chemotherapy resistance in high-grade serous ovarian cancer(HGSOC).Methods A Meta-analysis utilizing public ovarian cancer databases was performed to evaluate the correlation between MSLN expression levels and overall survival(OS)in ovarian cancer patients.Pathway enrichment analysis was employed to identify key signaling pathways regulated by MSLN and their roles in chemotherapy resistance.Additionally,the TCGA-HGSOC database was analyzed to examine genomic features associated with MSLN-mediated chemotherapy resistance.To validate the biological function of MSLN in chemotherapy resistance,an intraperitoneal metastasis model was established using MSLN-knockdown ID8 ovarian cancer cells in mice.Results Elevated MSLN expression was significantly associated with poor patient prognosis(HR:1.42,95%CI:1.16-1.74).Differential gene expression and pathway enrichment analyses revealed that high MSLN expression upregulates resistance-associated genes and pathways involved in drug metabolism and DNA-binding signaling.Genomic association analysis showed a negative correlation between high MSLN expression and chromosomal instability features,specifically CX3,CX11,and CX13 scores.In vivo studies demonstrated that MSLN knockdown enhanced the tumor-suppressive effects of cisplatin.Conclusion High MSLN expression represents a potential biomarker for poor prognosis and chemotherapy resistance in HGSOC patients,suggesting MSLN as a promising target for therapeutic intervention.