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 correlation between inflammation indicators(systemic inflammatory response syndrome and systemic immune-inflammation index)and adverse outcomes in patients with symptomatic stroke during hospitalization.Methods This study was a prospective cohort study including consecutive patients with symptomatic stroke who were hospitalized in Fuwai Hospital from January to September 2023.The past medical history,clinical symptoms and signs of the patients were collected.The neurological damage was evaluated with National Institute of Health Stroke Scale(NIHSS).Laboratory test results were recorded and the SIRI and SII in-dex were calculated.Patients were followed up for 90 days after the stroke,and their neurological outcomes were evaluated using the modified Rankin Scale.A score of 0-1 was classified as good outcome,and a score ≥2 was classified as poor outcome.The correlation between inflammatory response indicators and poor outcomes was as-sessed using multiple Logistic regression.Results A total of 97 patients with in-hospital symptomatic stroke were included with an average age of 61.8±12.7 years.Among them,there were 28 females(28.9％,28/97),9 with a history of prior stroke(9.3％,9/97),15 with atrial fibrillation(15.5％,15/97),16 with heart failure(16.5％,16/97),and 7 with myocardial infarction(7.2％,7/97).Correlation analysis showed that the NIHSS score at the time of stroke onset was significantly correlated with the patient's post-stroke SIRI(r=0.237,P＜0.05)and SII(r=0.234,P＜0.05).After 90 days of follow-up,41 cases(42.3％,41/97)had a poor outcome.Multiple Logistic regression analysis showed that post-stroke SIRI(Or=4.71,95％CI:1.24-17.90)and SII(Or=3.13,95％CI:0.88-11.06)were correlated with poor outcomes within 90 days after the stroke.Analysis using restricted cubic splines showed that as the levels of SIRI and SII increased,the risk of poor out-comes in patients with in-hospital symptomatic stroke increased.Conclusions SIRI is an independent risk factor for poor outcomes in patients with in-hospital symptomatic stroke,and the risk of poor neurological outcomes in-creases with high level of SIRI.

Objective To discuss the clinical value of flat head CT of two-way digital flat angiography system(DSA)in predicting symptomatic intracranial hemorrhage in patients with acute anterior circulation-large vessel occlusion cerebral infarction occurring within 24 hours after operation.Methods A total of 264 patients with acute anterior circulation-large vessel occlusion cerebral infarction,who were admitted to the Shanghai Changhai hospital to receive treatment from January 2020 to January 2023,were selected for this study.Mechanical thrombectomy was carried out in all the patients,and DSA flat head CT examination was performed 24 hours after operation.According to whether the postoperative DSA plate head CT scan showed high-density shadow or not,the patients were divided into observation group(showing high-density shadow,n=176)and control group(showing no high-density shadow,n=88).The clinical data,therapeutic regimen,and intracranial hemorrhage within 24 hours after operation were compared between the two groups.Taking head CT results as the standard,the clinical value of DSA flat head CT scan performed immediately after operation in predicting symptomatic intracranial hemorrhage occurring within 24 hours after operation was evaluated.Results Among the 264 patients with acute anterior circulation-large vessel occlusion cerebral infarction,118 patients developed intracranial hemorrhage within 24 hours after operation,including 24 patients(20.34％)having symptomatic intracranial hemorrhage.No statistically significant differences in clinical data and therapeutic regimen existed between the two groups(P＞0.05).The sensitivity,specificity and accuracy of DSA flat head CT scan performed immediately after operation in predicting intracranial hemorrhage occurring within 24 hours after operation in the observation group were 97.46％,58.22％and 75.76％respectively.The detection rate of symptomatic intracranial hemorrhage occurring within 24 hours after operation in the observation group was higher than that in the control group,the difference between the two groups were statistically significant(P＜0.05).The sensitivity,specificity and accuracy of DSA flat head CT scan performed immediately after operation in predicting symptomatic intracranial hemorrhage occurring within 24 hours after operation were 87.50％,57.48％and 40.15％respectively.The sensitivity,specificity and accuracy of DSA flat head CT scan in predicting the transformation of cerebral hemorrhage were 95.67％,63.12％and 80.23％respectively.Conclusion In patients with acute anterior circulation-large vessel occlusion cerebral infarction,who develop intracranial hemorrhage within 24 hours after mechanical thrombectomy,DSA flat head CT scan performed immediately after operation often shows high-density shadow,which is very helpful in predicting the risk of postoperative intracranial hemorrhage,the clinicians should make an early diagnosis and response to a possible symptomatic intracranial hemorrhage.

ObjectiveTo investigate the serotype distribution and antimicrobial resistance characteristics of foodborne Salmonella in infectious diarrhea cases in Minhang District, Shanghai, and to provide evidence for clinical diagnosis, treatment, prevention, and control of salmonellosis. MethodsFecal or anal swab samples were collected from foodborne diarrhea cases at sentinel hospitals between 2019 and 2023 in Minhang District of Shanghai. Salmonella was isolated, biochemically identified, and serotyped. Antimicrobial susceptibility testing was performed via the microbroth dilution method. ResultsA total of 4 294 samples were collected, from which 224 Salmonella strains were isolated, with an isolation rate of 5.22%. There was no gender difference in the positive rate of Salmonella. The positive rate showed seasonal fluctuations (χ²=160.475, P<0.001), with a higher positive rate in summer and autumn than in spring and autumn. Among different occupational groups, the positive rate was the highest among retired people (7.30%) (χ²=20.023, P=0.001). Among different age groups, the positive rate was the highest among those aged 80 years and above (7.33%) (χ²=13.491, P=0.009). A total of 28 serotypes were identified, with Salmonella Enteritidis being the most predominant, followed by Salmonella Typhimurium. Among them, 154 strains were multi-drug resistant to three or more types of antibiotics (68.75%). The most common drug resistance patterns among multi-drug resistant strains were ampicillin (AMP)-ampicillin/sulbactam (AMS)-sulfamethoxazole/trimethoprim (SXT)-chloramphenicol (CHL)-tetracycline (TET)-streptomycin (STR), AMP-TET-STR and AMP-AMS-TET-STR, with 9 strains being detected in each isolates. ConclusionThe positive rate of foodborne Salmonella in Minhang District, Shanghai, is high in summer and autumn, with a higher infection rate among retired people and those aged 60 years and above being the high-risk group. It is recommended to strengthen the protection for high-risk groups, implement targeted prevention and control measures in summer and autumn to reduce the risk of infection, and pay attention to guiding clinical medication and infection control.

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.

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: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.