ObjectiveTo investigate the influence of histone deacetylase 3 (HDAC3) on the occurrence, development of psoriasis-like inflammation in mice, and the relative immune mechanisms. MethodsHealthy C57BL/6 mice aged 6-8 weeks were selected and randomly divided into 3 groups: control group (Control), psoriasis model group (IMQ), and HDAC3 inhibitor RGFP966-treated psoriasis model group (IMQ+RGFP966). One day prior to the experiment, the back hair of the mice was shaved. After a one-day stabilization period, the mice in Control group was treated with an equal amount of vaseline, while the mice in IMQ group was treated with imiquimod (62.5 mg/d) applied topically on the back to establish a psoriasis-like inflammation model. The mice in IMQ+RGFP966 group received intervention with a high dose of the HDAC3-selective inhibitor RGFP966 (30 mg/kg) based on the psoriasis-like model. All groups were treated continuously for 5 d, during which psoriasis-like inflammation symptoms (scaling, erythema, skin thickness), body weight, and mental status were observed and recorded, with photographs taken for documentation. After euthanasia, hematoxylin-eosin (HE) staining was used to assess the effect of RGFP966 on the skin tissue structure of the mice, and skin thickness was measured. The mRNA and protein expression levels of HDAC3 in skin tissues were detected using reverse transcription real-time quantitative polymerase chain reaction (RT-qPCR) and Western blot (WB), respectively. Flow cytometry was employed to analyze neutrophils in peripheral blood and lymph nodes, CD4⁺ T lymphocytes, CD8⁺ T lymphocytes in peripheral blood, and IL-17A secretion by peripheral blood CD4⁺ T lymphocytes. Additionally, spleen CD4⁺ T lymphocyte expression of HDAC3, CCR6, CCR8, and IL-17A secretion levels were analyzed. Immunohistochemistry was used to detect the localization and expression levels of HDAC3, IL-17A, and IL-10 in skin tissues. ResultsCompared with the Control group, the IMQ group exhibited significant psoriasis-like inflammation, characterized by erythema, scaling, and skin wrinkling. Compared with the IMQ group, RGFP966 exacerbated psoriasis-like inflammatory symptoms, leading to increased hyperkeratosis. The psoriasis area and severity index (PASI) skin symptom scores were higher in the IMQ group than those in the Control group, and the scores were further elevated in the IMQ+RGFP966 group compared to the IMQ group. Skin thickness measurements showed a trend of IMQ+RGFP966>IMQ>Control. The numbers of neutrophils in the blood and lymph nodes increased sequentially in the Control, IMQ, and IMQ+RGFP966 groups, with a similar trend observed for CD4⁺ and CD8⁺ T lymphocytes in the blood. In skin tissues, compared with the Control group, the mRNA and protein levels of HDAC3 decreased in the IMQ group, but RGFP966 did not further reduce these expressions. HDAC3 was primarily located in the nucleus. Compared with the Control group, the nuclear HDAC3 content decreased in the skin tissues of the IMQ group, and RGFP966 further reduced nuclear HDAC3. Compared with the Control and IMQ groups, RGFP966 treatment decreased HDAC3 expression in splenic CD4⁺ and CD8⁺ T cells. RGFP966 treatment increased the expression of CCR6 and CCR8 in splenic CD4⁺ T cells and enhanced IL-17A secretion by peripheral blood and splenic CD4⁺ T lymphocytes. Additionally, compared with the IMQ group, RGFP966 reduced IL-10 protein levels and upregulated IL-17A expression in skin tissues. ConclusionRGFP966 exacerbates psoriatic-like inflammatory responses by inhibiting HDAC3, increasing the secretion of the cytokine IL-17A, and upregulating the expression of chemokines CCR8 and CCR6.

OBJECTIVE: To determine whether monotropein has an anticancer effect and explore its potential mechanisms against colorectal cancer (CRC) through network pharmacology and molecular docking combined with experimental verification. METHODS: Network pharmacology and molecular docking were used to predict potential targets of monotropein against CRC. Cell counting kit assay, plate monoclonal assay and microscopic observation were used to investigate the antiproliferative effects of monotropein on CRC cells HCT116, HT29 and LoVo. Flow cytometry and scratch assay were used to analyze apoptosis and cell cycle, as well as cell migration, respectively in HCT116, HT29, and LoVo cells. Western blotting was used to detect the expression of proteins related to apoptosis, cell cycle, and cell migration, and the expression of proteins key to the Akt pathway. RESULTS: The Gene Ontology and Reactome enrichment analyses indicated that the anticancer potential of monotropein against CRC might be involved in multiple cancer-related signaling pathways. Among these pathways, RAC-beta serine/threonine-protein kinase (Akt1, Akt2), cyclin-dependent kinase 6 (CDK6), matrix metalloproteinase-9 (MMP9), epidermal growth factor receptor (EGFR), cell division control protein 42 homolog (CDC42) were shown as the potential anticancer targets of monotropein against CRC. Molecular docking suggested that monotropein may interact with the 6 targets (Akt1, Akt2, CDK6, MMP9, EGFR, CDC42). Subsequently, cell activity of HCT116, HT29 and LoVo cell lines were significantly suppressed by monotropein (P<0.05). Furthermore, our research revealed that monotropein induced cell apoptosis by inhibiting Bcl-2 and increasing Bax, induced G₁-S cycle arrest in colorectal cancer by decreasing the expressions of CyclinD1, CDK4 and CDK6, inhibited cell migration by suppressing the expressions of CDC42 and MMP9 (P<0.05), and might play an anticancer role through Akt signaling pathway. CONCLUSION Monotropein exerts its antitumor effects primarily by arresting the cell cycle, causing cell apoptosis, and inhibiting cell migration. This indicates a high potential for developing novel medication for treating CRC.
Humans ; Proto-Oncogene Proteins c-akt/metabolism* ; Cell Proliferation ; Matrix Metalloproteinase 9 ; Molecular Docking Simulation ; Cell Cycle ; ErbB Receptors ; Apoptosis ; Colorectal Neoplasms/pathology* ; Cell Line, Tumor

Receptor-interacting serine/threonine-protein kinase 1 (RIPK1) functions as a key regulator in inflammation and cell death and is involved in mediating a variety of inflammatory or degenerative diseases. A number of allosteric RIPK1 inhibitors (RIPK1i) have been developed, and some of them have already advanced into clinical evaluation. Recently, selective RIPK1i that interact with both the allosteric pocket and the ATP-binding site of RIPK1 have started to emerge. Here, we report the rational development of a new series of type-II RIPK1i based on the rediscovery of a reported but mechanistically atypical RIPK3i. We also describe the structure-guided lead optimization of a potent, selective, and orally bioavailable RIPK1i, 62, which exhibits extraordinary efficacies in mouse models of acute or chronic inflammatory diseases. Collectively, 62 provides a useful tool for evaluating RIPK1 in animal disease models and a promising lead for further drug development.

The World Health Organization (WHO) released the “Global report on hypertension” on September 19, 2023. This report systematically summarizes the prevalence, mortality, diagnosis and treatment of hypertension in various countries, and elucidates the current situation of hypertension management, and gives a series of suggestions on how to manage hypertension, providing new thinking and inspiration for countries to optimize hypertension management. Through the summary of relevant studies and reports, this paper further reviews the present situation, early identification and management of hypertension.

Objective To investigate the imaging features of intestinal schwannoma(IS)in order to improve the diagnostic ability of the disease.Methods The clinical and imaging data of 14 patients with surgically and pathologically confirmed IS were retrospectively analyzed,including the location,size,morphology,nature,growth pattern,CT density,MRI signal,PET/CT metabolism and other characteristics of the tumors.Results Of the 14 IS cases,the lesions of 3 cases were located in the duodenum,2 cases in the cecum,8 cases in the colon and 1 case in the rectum.The lesions were all round or oval,with an average maximum diameter of(2.4±1.1)cm.The lesions were solid in 13 cases,extraluminal growth in 10 cases,cystic degeneration in 1 case and myxoid degeneration in 1 case.Chronic inflammatory lymph nodes were seen around the diseased intestines in 9 cases,and the short diameter of lymph nodes was greater than 5 mm in 6 cases.All 14 cases of IS showed low attenuation on plain CT scan,and progressive enhancement after contrast injection,including 1 case of mild enhancement,2 cases of moderate enhancement,and 11 cases of obvious enhancement.Two cases of IS showed low signal intensity on T1WI,slightly high signal intensity on T2WI,significantly high signal intensity on DWI,and obvious progressive enhancement after contrast injection on MRI.Two cases of IS showed high metabolism on 18F-FDG-PET/CT,and the SUVmax was 9.4 and 8.8,respectively.Conclusion The imaging findings of IS were characteristic to a certain extent.They mainly manifested as solid nodules or masses derived from the intestinal submucosa,with uniform attenuation or signal intensity,obvious progressive enhancement after contrast injection,obvious hypermetabolism on 18F-FDG-PET/CT,and slightly larger homogeneous lymph nodes were common around the lesions.

AIM To investigate the clinical effects of Jingu Xiaotong Powder combined with platelet-rich plasma on patients with knee osteoarthritis.METHODS Ninety-six patients were randomly assigned into control group(48 cases)for 8-week administration of platelet-rich plasma,and observation group(48 cases)for 8-week administration of both Jingu Xiaotong Powder and platelet-rich plasma.The changes in clinical effects,IL-17,SDF-1,TLR4,GSH-Px,NO,ox-LDL,WOMAC scores,TCM syndrome score,AIM2-SF score were detected.RESULTS The observation group demonstrated higher total effective rate than the control group(P<0.05).After the treatment,the two groups displayed decreased IL-17,SDF-1,TLR4,NO,ox-LDL,WOMAC scores,TCM syndrome score(P<0.05),and increased GSH-Px,AIM2-SF score(P<0.05),especially for the observation group(P<0.05).CONCLUSION For the patients with knee osteoarthritis,Jingu Xiaotong Powder combined with platelet-rich plasma can reduce IL-17,SDF-1,TLR4 levels,inhibit body inflammation,improve oxidative stress indices,alleviate pain,and enhance clinical efficacy and life quality.

Objective:To investigate the influencing factors of increased tube bleeding within 24 h after coronary artery bypass grafting(CABG) and its correlation with perioperative complications.Methods:This study was a prospective observational study. The patients with CABG surgery were enrolled in Beijing Anzhen Hospital affiliated to Capital Medical University from May 2018 to December 2021. The age, sex, complications, blood tests and other clinical data of outpatients were collected. Left ventricular ejection fraction(EF) and left ventricular enddiastolic diameter(LVED) were detected by echocardiography. MGF and PI of grafts were recorded during CABG. Perioperative troponin Ⅰ, blood clotting pentathlon, all-cause death, perioperative myocardial fraction, atrial fibrillation and stroke were collected. According to the tube bleeding within 24 h after operation, the patients were divided into increased group(tube bleeding>1 000 ml) and normal group(tube bleeding≤1 000 ml). The preoperative baseline data, intraoperative indexes and perioperative complications were compared between the two groups. Logistic regression, Spearman and linear regression models were used to analyze the correlation between tube bleeding within 24 h and clinical data.Results:304 patients underwent CABG were enrolled. There were 185 cases(60.9%) in the increased group and 119 cases(39.1%) in the normal group. After adjusting for age, sex and BMI, multivariate logistic regression analysis showed that male( OR=2.40, 95% CI: 1.38-4.18, P=0.002), history of stroke( OR=2.37, 95% CI: 1.07-5.26, P=0.034), and history of myocardial infarction( OR=1.81, 95% CI: 1.13-2.91, P=0.014) could significantly increase the risk of tube bleeding within 24 h after surgery. The average blood flow of the anterior descending branch( OR=0.99, 95% CI: 0.99-1.00, P=0.022) and the circumflex branch( OR=0.99, 95% CI: 0.98-1.00, P=0.003) during the operation was significantly negatively correlated with the increase of tube bleeding within 24 h after surgery, while the PI of anterior descending branch( OR=1.81, 95% CI: 1.26-2.61, P=0.001), circumflex branch( OR=1.45, 95% CI: 1.07-1.97, P=0.017), right coronary artery( OR=1.84, 95% CI: 1.29-2.62, P=0.001) were positively correlated with the increase of tube bleeding within 24 h after operation. In addition, prothrombin time significantly increased the risk of increased tube bleeding within 24 h after surgery( OR=1.16, 95% CI: 1.03-1.30, P=0.018). Linear regression analysis showed that there was a significant positive linear correlation between ICU time and tube bleeding within 24 h after surgery( OR=0.17, 95% CI: 0.96-4.58, P=0.003), and a significant negative linear correlation between postoperative ejection fraction and tube bleeding within 24 h( OR=-0.25, 95% CI: -33.18--13.07, P<0.001). Conclusion:Increased tube bleeding within 24 h after CABG is most common in males and patients with a history of cardiovascular and cerebrovascular infarction. Better graft hemodynamic parameters can reduce the tube bleeding within 24 h after the operation, further improve cardiac function and reduce ICU time.

ObjectiveTo analyze the satisfaction of service recipients with the preliminary assessment service of the unified elderly care needs evaluation in Shanghai， so as to provide reference for further optimization of the service system. MethodsA multi-stage random sampling method was employed to recruit participants. A total of 110 individuals who had received unified elderly care needs evaluation service in six districts of Shanghai were investigated using a structured questionnaire. SPSS 25.0 was used to analyze the data. Univariate analyses were conducted using the Chi-square test and Fisher’s precision probability test， while multivariate analysis was performed using ordinal regression. ResultsThere were differences in satisfaction with various aspects of the preliminary assessment process among participants from different areas， with those from outer suburbs generally exhibiting lower satisfaction （P<0.01）. Multivariate analysis results indicated that satisfaction with the timing of the preliminary assessment was related to the service recipients’ residential area and their primary source of income； satisfaction with the service attitude and capability of the assessment personnel was only related to the residential area. Satisfaction with the preliminary evaluation results was related to the participants’ marital status， educational level， income level， and the specific rating results. ConclusionThe satisfaction level with the preliminary assessment of the unified elderly care needs assessment in Shanghai is relatively high. In the process of evaluation， a deeper analysis and exploration of individual needs based on various personal information are essential to ensure the appropriateness of the provided elderly care services， and thereby effectively enhancing recipient satisfaction.

ObjectiveTo clarify the perception of the work and satisfaction levels among personnel conducting unified elderly care needs assessment in Shanghai， to analyze the factors influencing their job satisfaction， and to provide references for optimizing the job satisfaction of unified elderly care needs assessment personnel in Shanghai. MethodsA survey was conducted among 93 assessment personnel randomly selected from 29 elderly care needs assessment agencies in Shanghai. The personnel’s perception of their work and their levels of job satisfaction were examined. Chi-square test and Fisher’s precision probability test were used to compare regional differences， while the two-factor theory was employed to analyze the factors influencing job satisfaction. ResultsRegarding perception of the work， 92.5% of the surveyed personnel believed their work was important. Moreover， 87.1% were interested in their assessment tasks， and 84.9% believed they made a positive contribution to the assessment work and the assessment position was in line with their personal preferences. Regarding job satisfaction， 83.9% of the participants were satisfied with their assessment work， 78.5% considered the workload appropriate， and 74.2% found the working hours suitable. Additionally， 65.6% expressed satisfaction with the level of cooperation from the assessment subjects， while 94.6% and 91.4% of the personnel were satisfied with the support provided by the assessment agencies and had a sense of belonging， respectively. Furthermore， 65.6% of the personnel expressed satisfaction with their job compensation and benefits. Hygiene factors affecting job satisfaction included salary and compensation， workload， time spent on the job and institutional support related to external assistance， job suitability， teamwork， and client cooperation （P<0.05）， while motivational factors included recognition of the significance of the job， sense of achievement， interest in the job， sense of belonging， and opportunities for personal growth （P<0.05）. ConclusionThe overall work cognition and satisfaction of unified elderly care needs assessment personnel in Shanghai towards their work are relatively positive. Main issues include the heavy workload and actual job subsidies not meeting expectations. It is recommended to improve the standardization of the assessment process， establish a professional team of assessment personnel， and enhance the compensation and incentive mechanisms to continuously increase staff satisfaction.

AIM: To observe the changes of corneal densitometry(CD)in patients with keratoconus after corneal cross-linking(CXL).METHODS: Retrospective study. A total of 32 patients(43 eyes)with keratoconus in Ningxia Eye Hospital from April 2020 to April 2022 were selected. Pentacam analysis system divided the cornea into three layers: anterior 120 μm, middle layer and posterior 60 μm, and divides it into five regions with diameters of 0-2, 2-6, 6-10, 10-12 mm and full diameter according to the diameter, and measures the CD in different ranges. The changes of CD were compared before operation and at 1, 3 and 6 mo after operation.RESULTS: There were differences in uncorrected visual acuity, best corrected visual acuity and intraocular pressure before and 6 mo after operation(all P<0.05), and there was no difference in corneal endothelial cells(P=0.477). CD reached its peak at 1 mo after operation, and decreased at 3 mo and 6 mo after operation, but it was still higher than that before operation. There is a significant positive correlation between CD and Kmax in the anterior layer and the whole layer(r=0.164, P=0.016; r=0.152, P=0.023).CONCLUSION: The values of CD peaked at 1 mo after CXL, then it gradually decreased, tending to become stable at 6 mo postoperatively.