Acute lung injury (ALI) is a severe disease caused by viral infection that triggers an uncontrolled inflammatory response. This study investigated the capacity of jasurolignoside (JO), a natural compound, to bind to Toll-like receptor 4 (TLR4) and treat ALI. The anti-inflammatory properties of JO were evaluated in vitro through Western blotting, enzyme-linked immunosorbent assay (ELISA), immunofluorescence staining, and co-immunoprecipitation. The investigation utilized a lipopolysaccharide (LPS)-induced ALI animal model to examine the therapeutic efficacy and mechanism of JO in vivo. JO attenuated inflammatory symptoms in infected cells and tissues by modulating the NOD-like receptor family pyrin domain containing protein 3 (NLRP3) inflammasome and the nuclear factor κB (NF-κB)/mitogen-activated protein kinase (MAPK) pathway. Molecular docking simulations revealed JO binding to TLR4 active sites, confirmed by cellular thermal shift assay. Surface plasmon resonance (SPR) demonstrated direct interaction between JO and TLR4 with a Kd value of 35.1 μmol·L^-1. Moreover, JO inhibited tumor necrosis factor α (TNF-α), interleukin-1β (IL-1β), and IL-6 secretion and reduced leukocyte, neutrophil, lymphocyte, and macrophage infiltration in ALI-affected mice. JO also enhanced lung function and reduced ALI-related mortality. Immunohistochemical staining demonstrated JO's ability to suppress TLR4 expression in ALI-affected mouse lung tissue. This study establishes that JO can bind to TLR4 and effectively treat ALI, indicating its potential as a therapeutic agent for clinical applications.
Toll-Like Receptor 4/chemistry* ; Animals ; Acute Lung Injury/chemically induced* ; Mice ; Humans ; Ilex/chemistry* ; Molecular Docking Simulation ; Male ; NF-kappa B/immunology* ; Mice, Inbred C57BL ; NLR Family, Pyrin Domain-Containing 3 Protein/immunology* ; Tumor Necrosis Factor-alpha/genetics* ; Interleukin-1beta/genetics* ; RAW 264.7 Cells ; Disease Models, Animal

Objective To investigate the prognostic value of peripheral blood neutrophil-lymphocyte ratio(NLR)and thioredoxin reductase(TrxR)in patients with ovarian cancer receiving immunotherapy.Methods A total of 109 patients with advanced ovarian cancer treated in the Tumor Hospital Affiliated to Nantong University from January 2021 to December 2021 were selected as the research objects.The levels of NLR and TrxR in peripheral blood before immunotherapy were detected,and the evaluation value of NLR and TrxR on short-term efficacy,progression-free survival(PFS)and overall survival(OS)in ovarian cancer pa-tients receiving immunotherapy was explored.Results The optimal cut-off values of TrxR and NLR were 4.97 U/mL and 2.49%,respectively.According to the optimal cut-off value of TrxR and NLR,the patients were divided into the high level of TrxR group(69 cases,≥4.97 U/mL)and the low level of TrxR group(40 cases,<4.97 U/mL),the high level of NLR group(72 cases,≥2.49%)and the low level of NLR group(37 cases,<2.49%).The objective response rate(ORR)of the high level of NLR group was lower than that of the low level NLR group(P<0.05),and the disease progression rate(DPR)was higher than that of the low NLR group(P<0.05).The high level of TrxR group had a significantly lower ORR and a significantly higher DPR than the low level of TrxR group(P<0.05).The median PFS and OS of the high level of NLR group were 15.0 months and 16.0 months,respectively.The median PFS and OS of the low level of NLR group were 19.0 months and 21.0 months,respectively.The median PFS and OS of the high level of TrxR group were 15.0 months and 17.0 months,respectively.The median PFS was 18.0 months and the median OS was 21.0 months in the low level of TrxR group.NLR and TrxR were the influencing factors of PFS and OS in pa-tients with ovarian cancer immunotherapy(P<0.05).Conclusion The levels of NLR and TrxR in peripheral blood can be used as important prognostic indicators for advanced ovarian cancer patients receiving immuno-therapy.The lower the levels of NLR and TrxR,the better the prognosis of ovarian cancer patients.

Intestinal flora imbalance is closely related to the pathogenesis of rheumatoid arthritis (RA). The existing studies have explored the monomer components such as tripterygium glycosides, total glycosides of Chaenomeles speciosa, and triterpenoid saponins of Clematis, Chinese materia medica such as Tripterygium wilfordii, Caulis Sinomenii, Radix Paeoniae Alba, Fructus Gardeniae, Fructus Chebulae, Radix Ginseng, Radix et Rhizoma Rhei, Rhizoma Atractylodis Macrocephalae, Pterostilbene, and Ginger, as well as the mechanisms of Danggui Sini Decoction, Danggui Niantong Decoction, Duhuo Jisheng Decoction, Yunpi Jiedu Tongluo Qushi Decoction, Qingre Huoxue Decoction, Compound Fengshining, Qingre Yangyin Chushi Decoction, Aconitum Decoction, Zhijing Powder, Jinwu Jiangu Capsule, and Fermented Chinese Medicine Qushi Chubi Decoction in intervening RA by regulating intestinal flora, suggesting that Chinese materia medica can restore intestinal homeostasis, reduce joint inflammation and play a role in the prevention and treatment of RA by regulating immune response, improving intestinal mucosal barrier and regulating intestinal metabolites.

In the context of an aging society,the number of elderly cancer patients is constantly increasing,and geriatric oncology has garnered significant attention in recent years.Given the heterogeneity in the health status of older patients,it has become increasingly important to provide individualized diagnosis,treatment,follow-up,and care.Thus,it must be emphasized the Comprehensive Geriatric Assessment(CGA)for elderly patients,which encompasses their physical function,nutritional status,cognitive function,emotional state,comorbidities,polypharmacy,social situation,and treatment preferences.This article provides consensus recommendations on CGA tools for elderly patients prior to anticancer treatment,offering valuable references and insights for clinical practice in China.

Objective:To compare the effects of high-power and conventional power atrial fibrillation ablation on intraoperative acute pulmonary vein isolation, postoperative troponin levels, and atrial fibrillation recurrence.Methods:A retrospective selection was conducted on 105 patients with paroxysmal atrial fibrillation admitted to the Baoding NO.1 Central Hospital from January 2017 to December 2020. According to different treatment methods, they were divided into a high-power ablation group of 52 cases and a conventional power ablation group of 53 cases. The intraoperative rate of single circle acute pulmonary vein isolation, the recovery of electrical conduction after acute pulmonary vein isolation, and the location and number of points that need to be added were compared between the two groups; At the same time, two groups were compared in terms of surgical time, ablation time, surgical radiation exposure time and radiation dose, intraoperative complications postoperative cardiac troponin levels at 12 hours, and recurrence of atrial fibrillation within 1 year after ablation.Results:The intraoperative single loop pulmonary vein isolation rate and postoperative troponin levels in the high-power atrial fibrillation ablation group were higher than those in the conventional atrial fibrillation ablation group (all P<0.05). The surgical time, ablation time, and the number of sites and points that need to be added during surgery were less than those in the conventional atrial fibrillation ablation group (all P<0.05). There was no statistically significant difference in the incidence of intraoperative complications and postoperative atrial fibrillation recurrence between the two groups (all P>0.05). Conclusions:High power atrial fibrillation ablation has a higher single loop acute pulmonary vein isolation rate, fewer patch sites and points, shorter surgical time, and greater ablation damage compared to conventional ablation, and the clinical efficacy of the two groups is similar after surgery.

To explore the application of humanistic care in children's fever clinics,the children's fever clinics of Guangzhou Women and Children's Medical Center conducted relevant research using narrative medicine as a guiding concept.This paper elaborated on the medical humanistic dilemmas and narrative care needs in children's fever clinics,and focused on exploring the practice paths of narrative medicine in pediatric with Chinese characteristics from five dimensions,including the cultivation of nursing staff's abilities of professional narrative and humanistic care,the establishment of health lectures featuring narrative patient education,the alleviation of medical anxiety for children and their families,related support of narrative nursing,and caring services.The aim was to improve the narrative care ability of nurses in children's fever clinics,develop methods for pediatric patients that can eliminate the fear of seeking medical treatment,and protect children's physical and mental health.A carrier of care,support,and emotional expression can be provided for parents.The foundation for nursing staff to achieve professional growth through narrative reflection can be laid.Thus,it can assist in establishing a life narrative community relationship between doctors and patients,and jointly explore the meaning of life.

Background With the rapid industrialization, cadmium has become a primary heavy metal pollutant in cultivated land soil in China, which seriously affects human health. Previous studies have found that cadmium exposure associates with cognitive dysfunction in individuals, but there is a lack of research on the mechanism of cadmium exposure associated cognitive impairment in offspring in early life which is more vulnerable to various toxins and crucial for development of the neuro. Objective To explore the potential mechanism of brain-derived neurotrophic factor/tyrosine kinase receptor B (BDNF-TrkB) signaling pathway in cognitive dysfunction in mice after cadmium exposure in early-life. Methods Twelve 8-week-old C57BL/6 pregnant mice were randomly divided into 2 groups, namely control group and cadmium exposure group, with 6 mice in each group. The exposure period was from pregnancy day 4.5 to lactation day 21 (E4.5-P21), during which distilled water or cadmium chloride solution (2.5 mg·kg⁻¹·d⁻¹) was given. After lactation, the offspring of the control group and the cadmium exposure group were given distilled water until 8 weeks of age. Then the toxicity effects of cadmium exposure on mice were evaluated by body weight and selected biochemical indicators. The cadmium content in brain was detected and the learning and memory ability was tested by Y maze and Morris water maze to evaluate cognitive function of offspring mice. Histopathological changes of the hippocampus were observed after Nissl staining and Golgi staining. The mRNA and protein expression levels of the BDNF-TrkB pathway and synapse were detected by real-time quantitative PCR (qPCR) and Western blot. Results Compared with the control group, no significant change was found in body weight, liver or kidney function in the cadmium exposure group (P> 0.05). However, compared with the control group, the cadmium content in brain was increased in the cadmium exposure group (P<0.001). The behavioral changes associated with cognitive dysfunction were positive in the cadmium exposure group (all P<0.05). The histopathological observation after Nissl staining showed abnormal tissue structure, decreased number of neurons and increased karyopyknosis in the cadmium exposure group (P<0.01).The spine density of Golgi staining was decreased in the cadmium exposure group (P<0.001). The BDNF-TrkB pathway-related mRNA and the synapse-related mRNA in the hippocampus were reduced in the cadmium exposure group (all P<0.05). The expression levels of BDNF-TrkB pathway-related proteins and synapse-related proteins in the hippocampus were also reduced in the cadmium exposure group (P<0.05). Conclusion Early-life cadmium exposure may induce synaptic dysplasia and lead to cognitive dysfunction by down-regulating the BDNF-TrkB signaling pathway in mice.

Objectives:To compare the efficacy of transcatheter aortic valve replacement(TAVR)combined with percutaneous coronary intervention(PCI)versus surgical aortic valve replacement(SAVR)combined with coronary artery bypass grafting(CABG)in patients with intermediate or high risk severe aortic stenosis(AS)and coronary artery disease(CAD). Methods:Embase,Medline,the Cochrane Library,PubMed,VIP,Wanfang Database,CNKI were searched for studies comparing the efficacy of TAVR combined with PCI and SAVR combined with CABG in patients with intermediate or high risk severe aortic stenosis complicated with CAD,from the establishment of the database to July 4,2023. Results:Six studies were included,including one randomized controlled study and five observational cohort studies.A total of 2 137 patients were enrolled,including 833 in the TAVR+PCI group and 1 304 in the SAVR+CABG group.The results of the meta-analysis showed that compared with SAVR+CABG,TAVR+PCI did not significantly increase the risk of myocardial infarction(OR=0.65,95%CI:0.28-1.46,P=0.29),stroke(OR=0.81,95%CI:0.45-1.48,P=0.50)within 30 days and the risk of acute kidney injury(OR=0.38,95%CI:0.14-1.02,P=0.05),major bleeding(OR=0.66,95%CI:0.22-2.00,P=0.47)during follow-up,and significantly reduced all-cause mortality within 30 days(OR=0.66,95%CI:0.44-0.99,P=0.04),but significantly increased all-cause mortality(OR=1.47,95%CI:1.12-1.93,P=0.005)and vascular complications(OR=11.48,95%CI:2.69-48.94,P=0.001),pacemaker implantation(OR=3.09,95%CI:1.68-5.68,P<0.001)during long-term(≥2 years)follow-up. Conclusions:In patients with intermediate or high risk severe AS and CAD,compared with SAVR+CABG,TAVR+PCI significantly reduced the risk of all-cause mortality within 30 days,but significantly increased the risk of all-cause mortality,vascular complications,and pacemaker implantation during long-term follow-up.

Objective:To investigate the correlation between serum concentration of vasohibin-1 (VASH-1) and urinary albumin creatinine ratio (UACR) in patients with type 2 diabetes mellitus (T2DM) and diabetic nephropathy.Methods:The clinical data of 196 patients with T2DM from February 2017 to December 2020 were analyzed retrospectively. According to whether diabetic nephropathy (DN) was combined, 33 patients without DN of T2DM were divided into the control group,and 163 patients with DN of T2DM were divided into the case group, and the case group was divided into four groups:normal albuminuria group (groupⅠ, UACR <30 mg/g, 21 cases),microalbuminuria group (groupⅡ, UACR ≥30-≤300 mg/g, 50 cases), clinical albuminuria group (group Ⅲ, UACR>300 mg/g, 43 cases), and clinical albuminuria hypertensive group (groupⅣ, UACR >300 mg/g with hypertension, 49 cases). Serum levels of VASH-1,C-reactive protein(CRP), erythrocyte sedimentation rate (ESR) and transforming growth factor β1 (TGF-β1) with other biochemical indicators were measured. T-test was used for comparison between measurement data groups in accordance with normal distribution, one-way ANOVA was used for comparison between multiple groups, q-test was used for pairwise comparison, and χ2 test was used for comparison between counting data groups. The influencing factors were analyzed by multivariate Logistic regression.Pearson correlation analysis was used to analyze the correlation between vash-1 and UACR. Results:UACR((1 175.9±120.4) mg/g), CRP((9.80±2.01) mg/L), ESR((20.61±2.20) mm/h),TGF-β1((16.75±2.05) μg/L), VASH-1((645.3±183.5) ng/L) in case group were higher than that in the control group((11.5±2.0) mg/g, (4.77±1.34) mg/L, (8.33±1.56) mm/h, (10.63±1.97) μg/L, (416.3±162.1) ng/L), and there were significant differences between the two groups ( t=123.39,13.76,30.54,15.75,6.66; all P<0.001). Multivariate logistic regression analysis showed that VASH-1 ( OR=1.881,95% CI 1.146-3.089), UACR( OR=1.511,95% CI 1.064-2.146), TGF-β1( OR=1.846,95% CI 1.135-3.001)were all risk factors for DN of T2DM ( P values were 0.009, 0.022 and 0.012). Serum VASH-1 ((693.5±201.4), (709.8±214.7) ng/L] in group Ⅲ and group Ⅳ were higher than those in group Ⅰ and group Ⅱ ((585.3±162.1), (632.9±165.5) ng/L). There was significant difference between the two groups ( F=129.46, P<0.001). The CRP ((7.08±1.36), (8.99±3.72), (10.58±3.48), (11.64±3.50) mg/L), ESR ((17.36±1.76), (19.05±4.12), (21.45±5.74), (22.69±9.13) mm/h) and TGF- β1 ((14.75±1.97), (16.50±1.90), (17.06±1.23), (18.39±1.46) μg/L) of groupⅠ, groupⅡ, groupⅢ and groupⅣ increased gradually, and there were significant differences between the four groups ( F values were 73.48, 156.61, 25.83; all P<0.001). Pearson correlation analysis showed that there was a significant positive correlation between VASH-1 and UACR ( r=0.532, P=0.008). Conclusion:The concentration of VASH-1 in serum of patients with T2DM complicated with DN increased with the increase of UACR. VASH-1 may become a new marker for predicting early DN of T2DM.

【Objective】 To investigate the inhibitory effect of BFD-6b on colorectal cancer cell growth and its preliminary mechanism. 【Methods】 The inhibitory effect of BFD-6b on the growth of various tumor cells （SW480， MCF-7， T47D， SMMC-7721， BEL-7402， 97H， SK-HEP-1， H460， H1299， A549， MS751， and HELA） was investigated by MTT assay； the effect of BFD-6b on apoptosis and cell cycle was detected by flow cytometry； the effect of BFD-6b on the expressions of cell cycle-related proteins and apoptosis-related proteins was examined by Western blotting. 【Results】 BFD-6b inhibited the proliferation of different cancer cells such as SW480， MCF-7， H460， H1299， A549， and HELA. Among all of them， SW480 cells were most sensitive to BFD-6b， and the IC50 value was 7.09 μmol/L. Furthermore， BFD-6b could inhibit the growth of another three colorectal cell （SW620， Lovo， and HCT116 cells）； the IC50 values were 7.23， 8.08 and 8.96 μmol/L， respectively. BFD-6b could downregulate the amount of cyclinD1， cyclinE， and cell cycle-dependent kinase CDC2， thereby arresting the cell cycle at G1 phase. Also， BFD-6b downregulated the expressions of anti-apoptotic proteins Mcl-1 and Bcl-2， and upregulated the expressions of pro-apoptotic proteins BAK and BAX， thus inducing apoptosis of SW480 cells. 【Conclusion】 BFD-6b arrests SW480 cells at G1 phase by downregulating the expressions of cyclinD1， cyclinE and CDC2， and induces SW480 cell apoptosis by downregulating the expressions of Mcl-1 and Bcl-2 and upregulating the expressions of BAK and BAX， thereby inhibiting the proliferation of colorectal cancer SW480 cells.