Objective To investigate the regulatory effect of suppressor of cytokine signaling 1 (SOCS1) on the proliferation and apoptosis of myelodysplastic syndrome (MDS) cells SKM-1 and its potential mechanisms. Methods SOCS1 was overexpressed in SKM-1 cells by transfection with exogenous SOCS1-overexpressing plasmid. Cell viability, cell cycle and apoptosis were analyzed with CCK-8 and flow cytometry assays, respectively. Western blot was used to evaluate the expression of proteins related to the Janus kinase 2/signal transducer and activator of transcription (JAK2/STAT) signaling pathway. Additionally, a NOD/SCID mouse model of MDS was established to record mouse body weight and survival time, assessing the impact of the SOCS1 gene on the growth of SKM-1 cells in vivo. Results Transfection of the SOCS1-overexpressing plasmid significantly increased the mRNA and protein expression levels of SOCS1 in the MDS cell line SKM-1. Overexpression of SOCS1 remarkably reduced cell viability, inhibited cell proliferation, and promoted apoptosis of SKM-1 cells, which also decreased the expression of phosphorylated-JAK2 (p-JAK2), phosphorylated-STAT3 (p-STAT3), and p-STAT5 proteins. Furthermore, in vivo experiment results showed that the body weight and survival time of mice in the SOCS1 overexpression group were significantly better than those in the MDS model group, and the number of CD45⁺ SKM-1 cells in the peripheral blood was significantly lower than that in the MDS model group, indicating that SOCS1 overexpression could inhibit the activity of SKM-1 cells in mice. Western blot results verified the protein expression level of SOCS1 in the bone marrow of mice in the SOCS1 overexpression group was significantly higher than that in the MDS model group, while the protein expression levels of p-JAK2, p-STAT3, and p-STAT5 were significantly lower than those in the MDS model group. Conclusion SOCS1 inhibits the proliferation of MDS cell line SKM-1 and promotes its apoptosis by negatively regulating the JAK2/STAT signaling pathway, making it a potential therapeutic target for myelodysplastic syndromes.
Animals ; Humans ; Mice ; Apoptosis ; Body Weight ; Bone Marrow/metabolism* ; Janus Kinase 2/metabolism* ; Mice, Inbred NOD ; Mice, SCID ; Myelodysplastic Syndromes/metabolism* ; Phosphorylation ; STAT3 Transcription Factor/metabolism* ; STAT5 Transcription Factor/metabolism* ; Suppressor of Cytokine Signaling 1 Protein/metabolism* ; Cell Proliferation

Recent data suggest that vascular endothelial growth factor receptor inhibitor (VEGFRi) can enhance the anti-tumor activity of the anti-programmed cell death-1 (anti-PD-1) antibody in colorectal cancer (CRC) with microsatellite stability (MSS). However, the comparison between this combination and standard third-line VEGFRi treatment is not performed, and reliable biomarkers are still lacking. We retrospectively enrolled MSS CRC patients receiving anti-PD-1 antibody plus VEGFRi (combination group, n=54) or VEGFRi alone (VEGFRi group, n=32), and their efficacy and safety were evaluated. We additionally examined the immune characteristics of the MSS CRC tumor microenvironment (TME) through single-cell and spatial transcriptomic data, and an MSS CRC immune cell-related signature (MCICRS) that can be used to predict the clinical outcomes of MSS CRC patients receiving immunotherapy was developed and validated in our in-house cohort. Compared with VEGFRi alone, the combination of anti-PD-1 antibody and VEGFRi exhibited a prolonged survival benefit (median progression-free survival: 4.4 vs. 2.0 months, P=0.0024; median overall survival: 10.2 vs. 5.2 months, P=0.0038) and a similar adverse event incidence. Through single-cell and spatial transcriptomic analysis, we determined ten MSS CRC-enriched immune cell types and their spatial distribution, including naive CD4⁺ T, regulatory CD4⁺ T, CD4⁺ Th17, exhausted CD8⁺ T, cytotoxic CD8⁺ T, proliferated CD8⁺ T, natural killer (NK) cells, plasma, and classical and intermediate monocytes. Based on a systemic meta-analysis and ten machine learning algorithms, we obtained MCICRS, an independent risk factor for the prognosis of MSS CRC patients. Further analyses demonstrated that the low-MCICRS group presented a higher immune cell infiltration and immune-related pathway activation, and hence a significant relation with the superior efficacy of pan-cancer immunotherapy. More importantly, the predictive value of MCICRS in MSS CRC patients receiving immunotherapy was also validated with an in-house cohort. Anti-PD-1 antibody combined with VEGFRi presented an improved clinical benefit in MSS CRC with manageable toxicity. MCICRS could serve as a robust and promising tool to predict clinical outcomes for individual MSS CRC patients receiving immunotherapy.
Humans ; Colorectal Neoplasms/drug therapy* ; Male ; Female ; Immunotherapy ; Middle Aged ; Aged ; Tumor Microenvironment/immunology* ; Retrospective Studies ; Microsatellite Instability ; Transcriptome ; Single-Cell Analysis ; Programmed Cell Death 1 Receptor/immunology* ; Gene Expression Profiling ; Immune Checkpoint Inhibitors/therapeutic use* ; Adult ; Receptors, Vascular Endothelial Growth Factor/antagonists & inhibitors*

Cannabidiol (CBD), a non-psychoactive cannabinoid, shows great promise in treating methamphetamine (METH) addiction. Nonetheless, the molecular target and the mechanism through which CBD treats METH addiction remain unexplored. Herein, CBD was shown to counteract METH-induced locomotor sensitization and conditioned place preference. Additionally, CBD mitigated the adverse effects of METH, such as cristae loss, a decline in ATP content, and a reduction in membrane potential. Employing an activity-based protein profiling approach, a target fishing strategy was used to uncover CBD's direct target. ATP5A1, a subunit of ATP synthase, was identified and validated as a CBD target. Moreover, CBD demonstrated the ability to ameliorate METH-induced ubiquitination of ATP5A1 via the D376 residue, thereby reversing the METH-induced reduction of ATP5A1 and promoting the assembly of ATP synthase. Pharmacological inhibition of the ATP efflux channel pannexin 1, blockade of ATP hydrolysis by a CD39 inhibitor, and blocking the adenosine A1 receptor (A1R) all attenuated the therapeutic benefits of CBD in mitigating METH-induced behavioral sensitization and CPP. Moreover, the RNA interference of ATP5A1 in the ventral tegmental area resulted in the reversal of CBD's therapeutic efficacy against METH addiction. Collectively, these data show that ATP5A1 is a target for CBD to inhibit METH-induced addiction behaviors through the ADO-A1R signaling pathway.

Objective To analyze the influencing factors of clinical pregnancy and live birth rates in patients undergoing frozen-thawed embryo transfer(FET)for the first time.Methods The clinical data of 1 458 patients who underwent FET cycle-assisted pregnancy for the first time were retrospectively analyzed and divided into four groups according to clinical pregnancy and live bith outcomes.The clini-cal data were compared to analyze the factors affecting clinical pregnancy and live birth rates in FET cycles that were included in multiple logistic regression analysis.Results Of the 1458 cycles,the clinical pregnancy and live birth rates were 44.0% and 34.0%,respectively.The mean age of the clinical pregnancy and live birth groups was lower than that in non-clinical pregnancy and stillbirth groups(P<0.05).The clinical pregnancy and live birth rates of patients aged<35 years were higher than those aged≥35 years(P<0.05).The clinical preg-nancy and live birth rates of patients with≥8 mm endometrial thickness were higher than those with<8 mm endometrial thickness(P<0.05).The clinical pregnancy rate of natural cycles of endometrial preparation regimen was higher than that of HRT cycles(P<0.05).The clinical pregnancy and live birth rates of double-embryo transfers were higher than that of single-embryo transfers(P<0.05).The clinical pregnancy and live birth rates of blastocyst transfers were higher than those of cleavage stage(P<0.05).Conclusion Age,endometrial thickness,number of transplanted embryos,and embryo morphology were the independent factors influencing clinical pregnancy and live birth outcomes during FET cycle transplantation.

Objective:To develop and test the reliability and validity of the scale of nurses′ medication competence. To provide scientific basis for the safe medication management of clinical nurses.Methods:Based on the qualitative interview results, combined with role theory and core competence theory, the initial item pool of the scale was formed through literature analysis and discussion in the research group. The first draft of the scale was formed through expert correspondence and pre-investigation. Using the cross-sectional survey methed, from October to November 2022, a questionnaire survey was conducted among 825 clinical nurses from 6 tertiary hospitals in Dalian by convenience sampling method to test the reliability and validity of the scale.Results:Totally 20 experts were consulted, aged 35-49 years old. The nurses′ medication competence evaluation scale contained 11 dimensions, including pharmacological knowledge, medication management ability, medication evaluation ability, medication order checking and execution ability, clinical practice ability, modern technology application ability, educational consulting ability, communication and coordination ability, scientific research and learning ability, ethical and legal practice ability, quality management and risk management ability, with a total of 50 items. Exploratory factor analysis identified 11 common factors, which accounted for 86.525% of the variance. The Cronbach α coefficient of the scale was 0.975, the Cronbach α coefficient of all dimensions were 0.880-0.977, and the retest reliabilities were 0.721-0.875. The content validity index of the scale was 0.99, and the content validity index of all items were 0.83-1.00. The correlation coefficients between the scale and the Competency Inventory for Registered Nurse were 0.636-0.938. Conclusions:The nurses′ medication competence evaluation scale had good reliability and validity, and could be used as an effective tool to evaluate the medication ability of nurses.

Objective The equilibrium solubility and oil-water partition coefficient of caffeic acid in different pH environments were determined,and its biopharmaceutical classification system(BCS)classification was speculated.The dissolution curve of caffeic acid tablets was determined,and the above parameters were substituted into the rat PBPK model for modeling.Gastroplus software was used to predict the in vitro and in vivo correlation of caffeic acid tablets.Methods Quantitative analysis of caffeic acid was performed by a high-performance liquid chromatography in this research,the chromatographic column was Agilent Eclipse Plus C18(4.6 mm×250 mm,5 μm),the mobile phase was 0.32%glacial acetic acid solution-methanol(70∶30),the flow rate was 1.0 mL·min-1,the detection wavelength was 323 nm,the column temperature was 25℃,the injection volume was 10 μL.The equilibrium solubility,solubility volume(DSV)and oil-water partition coefficient(P)of caffeic acid in different pH buffers were measured by the shake flask method and n-octanol-water system,and its BCS classification was speculated.The dissolution curves of caffeic acid tablets in water,pH1.2,pH4.5 and pH6.8 were determined.The Z-Factor values of these dissolution curves were analyzed using Gastroplus software.The relevant parameters were substituted into the physiological pharmacokinetic(PBPK)model of rats to simulate the in vivo pharmacokinetic(PK)curve of rats.Compared with the measured PK curve that was reported previously,the correlation between in vivo and in vitro was speculated.Results The equilibrium solubility of caffeic acid in pH1.2,pH4.5 and pH6.8 were 0.676,1.266 and 4.624 mg·L-1,and the DSV were 443 787,236 967 and 64 879 mL,which showed that caffeic acid was an insoluble drug which had a strong pH dependence in dissolution;The oil-water partition coefficients(P)of caffeic acid in water,pH1.2 buffer,pH4.5 buffer and pH6.8 buffer were 4.33(logP=0.64),28.87(logP=1.46),19.77(logP=1.30)and 0.28(logP=-0.56),which indicated that caffeic acid was a BCS Ⅱ drug with high permeability.The results of the Cmax,tmax and AUC of caffeic acid in rats obtained by a software simulation was 0.358 μg·mL-1,0.39 h and 0.320 μg·h-1·mL-1,which was basically matched with the results[Cmax∶(0.250±0.037)μg·mL-1、tmax∶(0.33±0.12)h、AUC∶(0.303±0.024)μg·h-1·mL-1]that reported previously,so was the PK curves.Conclusion Caffeic acid is a drug with low solubility and high permeability.It is speculated that caffeic acid is a BCS Ⅱ drug,and its tablets show a high correlation in vivo and in vitro in rats.

Objective To observe the value of motion freeze technology(MFT)for improving the quality of cone-beam CT(CBCT)images of renal artery aneurysms.Methods Twenty patients with renal artery aneurysms who would receive transcatheter arterial embolization were prospectively enrolled.Renal artery angiography was performed under the guidance of CBCT,and motion artifacts were processed using MFT.Then subjective and objective evaluation of images before and after MFT correction were performed,aimed on displaying of renal artery,parent artery and vascular tree in target area,and the mean value(mean)and standard deviation(SD)of unit density pixels,margin sharpening error rate of blood vessels were measured and calculated.Results After MFT correction,the displaying of renal artery on maximum intensity projection images and parent artery on reconstructed CBCT images were significantly better than those before correction(both P＜0.05),clear vascular trees could be automatically extracted using Flightplan for Liver software,SD and margin sharpening error rate of blood vessels of renal artery aneurysm significantly decreased but mean significantly increased on CBCT images(all P＜0.05).Conclusion MFT could effectively improve the quality of CBCT images of renal artery aneurysms.

Objective:To conduct a scoping review of the characteristics, functions, risk of bias and applications of home-based self-management behavior assessment tools for lung transplant patients, so as to provide references for clinical medical staff to conduct further related research.Methods:The relevant literatures were systematically searched in China National Knowledge Infrastructure, Wanfang Database, VIP, China Biology Medicine disc, PubMed, Web of Science Core Collection, Embase, Cochrane Library and CINAHL databases. The search period was from the establishment of the databases to June 30, 2023. The scoping review method framework was used to screen the literature, extract information and standardize the report.Results:A total of 10 167 Chinese and English literatures were searched, and after deduplication and screening, 23 articles that met the criteria were finally included, involving 13 home-based self-management behavior assessment tools for lung transplant patients, including nine specific tools and four universal tools. There were eight kinds of lung transplantation patients whose reliability and validity were not verified. Of the 13 tools, those with single-dimensional assessments and single measures predominate. The level of home self-management behavior of lung transplant patients was reflected mainly through compliance, and medication management was the most frequently assessed content.Conclusions:At present, the measurement of home-based self-management behavior of lung transplant patients is mainly based on questionnaire surveys, and the evaluation tools are mostly single dimensional. The reliability and validity of most evaluation tools in the population of lung transplant patients are not yet clear, and there is a certain risk of bias. It is recommended that researchers pay attention to the reliability and validity verification report of the evaluation tool in the target population when selecting it, and integrate multiple measurement methods to reduce measurement errors.

ObjectiveTo reveal the effects of Huanglian Jiedutang （HLJDT） on the learning and memory abilities of APP/PS1 transgenic mice via hypoxia-inducible factor-1α （HIF-1α）/vascular endothelial growth factor （VEGF） signaling pathway. MethodForty 5-month-old β-amyloid precursor protein （APP）/presenilin 1（PS1） mice were randomized into the model， donepezil （0.001 g·kg^-1·d^-1）， and low-， medium-， and high-dose （1.5， 3， 6 g·kg^-1·d^-1， respectively） HLJDT groups， and 8 C57BL/6 mice were taken as the normal group. After 45 days of continuous administration， Morris water maze test was conducted， and the organ indexes were calculated. The morphological structure of cerebral vascular endothelial cells in mice was observed under a transmission electron microscope. Western blot was employed to measure the protein levels of APP， HIF-1α， VEGF，VEGFA， and brain-derived neurotrophic factor （BDNF） in the hippocampus. The mRNA levels of APP， HIF-1α， and VEGF were determined by real-time fluorescence quantitative polymerase chain reaction （Real-time PCR）. ResultCompared with the normal group， the model group showed prolonged escape latency （P<0.05）， reduced distance and time around the target platform （P<0.05）， decrease brain and spleen indexes （P<0.05）， vascular endothelial cells with karyopyknosis and not abundant cytoplasm， up-regulated protein levels of APP， HIF-1α， VEGF， and VEGFA （P<0.05）， down-regulated protein level of BDNF （P<0.05）， and up-regulated mRNA levels of APP， HIF-1α， and VEGF （P<0.05） in the hippocampus. Compared with the model group， high-dose HLJDT shortened the escape latency （P<0.05）， increased the distance and time around the target platform （P<0.05）， raised the brain and spleen indexes （P<0.05）， repaired the organelles of vascular endothelial cells， down-regulated the protein levels of APP， HIF-1α， VEGF， and VEGFA （P<0.05）， up-regulated the protein level of BDNF （P<0.05）， and down-regulated the mRNA levels of APP， HIF-1α， and VEGF （P<0.05） in the hippocampus. ConclusionHLJDT can improve the learning and memory abilities of mice by reducing the expression of HIF-1α and VEGF， thus protecting the nerves.

Objective To investigate the effect of residual corneal astigmatism on visual acuity after regional refrac-tive intraocular lens(IOL)implantation.Methods A retrospective cohort study was conducted.The medical records and follow-up data of 73 eyes of 57 cataract patients who underwent ultrasound emulsification cataract extraction combined with LENTIS Comfort LS-313 MF15 IOL implantation in the Ophthalmology Department of the Hebei General Hospital from June 2020 to March 2022 were collected.These patients were grouped according to postoperative residual corneal astigmatism:32 patients(40 eyes)with a residual corneal astigmatism of 0.75(exclusive)-1.50 D were taken as the experimental group,and 25 patients(33 eyes)with a residual corneal astigmatism ≤0.75 D were taken as the control group.The uncor-rected distance visual acuity(5 m),uncorrected intermediate visual acuity(80 cm),uncorrected near visual acuity(40 cm),out-of-focus curve,objective visual quality,subjective visual quality,satisfaction degree and lens removal rate of pa-tients in the two groups were recorded 6 months postoperatively.Results The postoperative uncorrected distance visual acuity(logMAR)was 0.10(0.00,0.22),the uncorrected intermediate visual acuity(logMAR)was 0.00(0.00,0.10),and the uncorrected near visual acuity(logMAR)was 0.20(0.10,0.30)and 0.20(0.10,0.20)in the experimental and control groups,with no statistically significant differences(all P＞0.05).The postoperative out-of-focus curves showed that the distance visual acuity of patients with additional spherical equivalent refraction ranged from+2.00 D to-4.00 D in the two groups had no statistically significant difference(all P＞0.05).There were statistically significant differences in to-tal aberration,coma aberration,modulation transfer function and Strehl ratio in the objective visual quality of patients after surgery(all P＜0.05),and there was no statistically significant difference in the total higher-order aberration,spherical ab-erration and cloverleaf aberration(all P＞0.05).There was no statistically significant difference in the subjective visual quality,satisfaction degree and lens removal rate in the two groups(all P＞0.05).Conclusion Residual corneal astig-matism of 0.75 D to 1.50 D after LENTIS Comfort LS-313 MF15 IOL implantation has no effect on higher-order aberration,spherical aberration,and cloverleaf aberration in subjective and objective visual quality,and has an impact on total aberra-tion,coma aberration,modulation transfer function and Strehl ratio in objective visual quality.