Ganlu formula ethyl acetate extract (GLEE) blocked the development of experimental arthritis by inhibiting NLRP3 activation and reducing M1 type macrophage polarization.

ETHNOPHARMACOLOGICAL RELEVANCE: The Tibetan medicine Ganlu Formula, as a classic prescription, is widely used across the Qinghai-Tibet Plateau area of China, which has a significant effect on relieving the course of rheumatoid arthritis (RA). However, the active compounds and underlying mechanisms of Ganlu Formula in RA treatment remain largely unexplored. AIM OF THE STUDY: This study aimed to elucidate the active substances and potential mechanisms of the ethyl acetate extract of Ganlu Formula ethyl acetate extract (GLEE) in the treatment of RA. MATERIALS AND METHODS: Ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS) was utilized to analyze and identify the chemical constituents within GLEE. Discovery Studio molecular virtual docking technology was utilized to dock the interaction of GLEE with inflammation-related pathway proteins. The GLEE gene library was obtained by transcriptome sequencing. Collagen-induced arthritic（CIA) rats were utilized to assess the antiarthritic efficacy of GLEE. Micro-CT imaging was employed to visualize the rat paw, and ultrasound imaging revealed knee joint effusion. Evaluation of synovial tissue pathological changes was conducted through hematoxylin-eosin staining and saffranine solid green staining, while immunohistochemical staining was employed to assess NLRP3 expression along with inflammatory markers. Immunofluorescence staining was utilized to identify M1 macrophages. RESULTS: Metabolomic analysis via UPLC-Q-TOF-MS identified 28 potentially bioactive compounds in GLEE, which interacted with the active sites of key proteins such as NLRP3, NF-κB, and STAT3 through hydrogen bonds, C-H bonds, and electrostatic attractions. In vitro analyses demonstrated that GLEE significantly attenuated NLRP3 inflammasome activation and inhibited the polarization of bone marrow-derived macrophages (BMDMs) towards the M1 phenotype. In vivo, GLEE not only prevented bone mineral density (BMD) loss but also reduced ankle swelling in CIA rats. Furthermore, it decreased the expression of the NLRP3 inflammasome and curtailed the release of inflammatory mediators within the knee joint. CONCLUSION: GLEE effectively mitigated inflammatory responses in both blood and knee synovial membranes of CIA rats, potentially through the down-regulation of the NLRP3/Caspase-1/IL-1ß signaling pathway and reduction in M1 macrophage polarization.

Dendritic Polylysine with Paclitaxel and Triptolide Codelivery for Enhanced Cancer Ferroptosis through the Accumulation of ROS.

Recently, paclitaxel (PTX) was reported to increase intracellular lipid reactive oxygen species (ROS) levels, triggering cancer cell ferroptosis. Based on this, some efforts had been made to improve PTX treatment for non-small-cell lung cancer (NSCLC). Our previous studies demonstrated that triptolide (TPL) could improve the antitumor effect of PTX. Nevertheless, the poor solubility and side effects often limit the application of chemotherapy drugs. In this paper, we constructed a novel nanodrug delivery system (NDDS) chemosynthesis by PEGylated generation 3 (G3) dendritic polylysine coloaded with PTX and TPL (PTX-TPL-PEG-PLL, PTPP), which was endowed with the ability of tumor targeting and favorable solubility. In addition, we demonstrated that TPL could induce ROS generation by regulating the NF-κB signaling pathway to enhance the ferroptosis-induced effect of PTX. Besides, ferroptosis induced by PTPP could improve chemoresistance through inhibiting the level of P-gp, GPX4, and SLC7A11. Furthermore, we determined that ferroptosis may strengthen the immune response by increasing the expression of CD8+ T cells and IFN-γ+ cells while decreasing Treg cells. In general, PTPP may be a potential system for NSCLC treatment.

Positive psychological capital, post-traumatic growth, social support, and quality of life in patients with systemic lupus erythematosus: A cross-sectional study.

OBJECTIVE: This study aimed to investigate the correlation between positive psychological capital, post-traumatic growth, social support, and quality of life (QOL) in patients with systemic lupus erythematosus (SLE). METHODS: A cross-sectional study was conducted at the First Affiliated Hospital of Xinjiang Medical University from October 2022 to May 2023. A sample of 330 hospitalized SLE patients was selected for this study. The collected data included demographic information, the SLE disease activity index, the Positive Mental Capital Questionnaire, the Chinese version of the Post-Traumatic Growth Scale, the Social Support Rating Scale, and the Chinese version of the Lupus Quality of Life Scale. RESULTS: The QOL score among the 330 SLE patients was measured as M(P25, P75) of 105 (83.00,124.00). Positive psychological capital, post-traumatic growth, and social support demonstrated significant positive correlations with the QOL in SLE patients (p < 0.05). Multiple linear regression analysis revealed that literacy, disease level, disease duration, occupation, marital status, psychological capital, social support, and post-traumatic growth were influential factors associated with the QOL in SLE patients. CONCLUSION: Medical professionals should be attentive to the psychological well-being of SLE patients and should consider implementing early psychological interventions. These interventions are crucial for enhancing the QOL for individuals diagnosed with SLE.

Integration of bulk RNA sequencing to reveal protein arginine methylation regulators have a good prognostic value in immunotherapy to treat lung adenocarcinoma.

Background: Given the differential expression and biological functions of protein arginine methylation (PAM) regulators in lung adenocarcinoma (LUAD), it may be of great value in the diagnosis, prognosis, and treatment of LUAD. However, the expression and function of PAM regulators in LUAD and its relationship with prognosis are unclear. Methods: 8 datasets including 1798 LUAD patients were selected. During the bioinformatic study in LUAD, we performed (i) consensus clustering to identify clusters based on 9 PAM regulators related expression profile data, (ii) to identify hub genes between the 2 clusters, (iii) principal component analysis to construct a PAM.score based on above genes, and (iv) evaluation of the effect of PAM.score on the deconstruction of tumor microenvironment and guidance of immunotherapy. Results: We identified two different clusters and a robust and clinically practicable prognostic scoring system. Meanwhile, a higher PAM.score subgroup showed poorer prognosis, and was validated by multiple cohorts. Its prognostic effect was validated by ROC (Receiver operating characteristic curve) curve and found to have a relatively good prediction efficacy. High PAM.score group exhibited lower immune score, which associated with an immunosuppressive microenvironment in LUAD. Finally, patients exhibiting a lower PAM.score presented noteworthy therapeutic benefits and clinical advantages. Conclusion: Our PAM.score model can help clinicians to select personalized therapy for LUAD patients, and PAM.score may act a part in the development of LUAD.

Prognostic significance of alveolar collapse in lung invasive adenocarcinoma and its relationship with tumor infiltrating lymphocytes.

This study aims to investigate the correlations between alveolar collapse, tumor size, and tumor infiltrating lymphocytes (TILs), while also evaluating the prognostic significance of alveolar collapse in invasive lung adenocarcinoma. 355 patients with solitary invasive lung adenocarcinoma were divided into two groups based on the maximum diameter of alveolar collapse: alveolar collapse ≤ 5 mm group and alveolar collapse > 5 mm group. Differences in clinicopathological characteristics, tumor size, TILs, and prognosis were compared between the two groups. The alveolar collapse > 5 mm group had a higher mean age, larger tumor diameter, and increased TILs levels compared to the alveolar collapse ≤ 5 mm group (P < 0.05). A moderate positive correlation was observed between alveolar collapse and tumor size (r = 0.646, P < 0.001). Lung adenocarcinoma with alveolar collapse > 5 mm demonstrated superior 5-year survival and acted as an independent prognostic indicator (HR=0.152, P = 0.004) in multivariate Cox regression analysis, alongside tumor size (HR=10.172, P = 0.034) and lymph node metastasis (HR=2.88, P = 0.017). The size of alveolar collapse is associated with TILs abundance, suggesting that the immune microenvironment may play a crucial role in alveolar collapse formation. Pathologists should take note of alveolar collapse in lung adenocarcinoma.

Micropapillary Pattern in Invasive Mucinous Adenocarcinoma of the Lung: Comparison With Invasive Non-Mucinous Adenocarcinoma.

Background. The presence of a micropapillary pattern is associated with poor outcomes in lung adenocarcinoma. This study aimed to assess the clinicopathological features of micropapillary pattern in mucinous adenocarcinoma of the lung. Methods. The patients were stratified into three groups: the invasive mucinous adenocarcinoma group (60 patients), the mixed invasive mucinous adenocarcinoma group (33 patients), and the invasive non-mucinous adenocarcinoma group (237 patients). The presence of micropapillary pattern and its clinicopathological features were analyzed and compared between the three groups. Results. Compared to mixed invasive mucinous adenocarcinoma, invasive mucinous adenocarcinoma had lower frequencies of micropapillary pattern (28.3% vs 87.9%, respectively; P < .001) and lymph node metastasis (00.0% vs 15.1%, respectively; P = .005). The frequency of tumor spread through air space (STAS) in invasive mucinous adenocarcinoma (23.3%) was higher than that in invasive non-mucinous adenocarcinoma (6.3%; P < .001), while lower than that in mixed invasive mucinous adenocarcinoma (60.6%; P < .001). When the three groups were all accompanied by micropapillary pattern, there was no obvious difference in STAS between invasive mucinous adenocarcinoma with micropapillary pattern and mixed mucinous adenocarcinoma with micropapillary pattern (P > .05). No filigree pattern occurred in invasive mucinous adenocarcinoma with micropapillary pattern. Conclusions. The micropapillary pattern is frequently observed in invasive mucinous adenocarcinoma and has a better prognosis compared to mixed invasive mucinous adenocarcinoma and invasive non-mucinous adenocarcinoma. However, the malignancy of the micropapillary pattern in mixed mucinous adenocarcinoma was similar to that in invasive non-mucinous adenocarcinoma, even with the presence of mucus. These findings suggest that the development mechanisms of the micropapillary pattern in invasive mucinous adenocarcinoma and mixed mucinous adenocarcinoma may differ.

Enhanced Antitumor Efficacy of Novel Biomimetic Platelet Membrane-Coated Tetrandrine Nanoparticles in Nonsmall Cell Lung Cancer.

Nonsmall cell lung cancer (NSCLC) remains one of the leading causes of cancer-related death worldwide, posing a serious threat to global health. Tetrandrine (Tet) is a small molecule in traditional Chinese medicine with proven primary efficacy against multiple cancers. Although previous studies have demonstrated the potential anticancer effects of Tet on NSCLC, its poor water solubility has limited its further clinical application. Herein, a novel nanoparticle-based drug delivery system, platelet membrane (PLTM)-coated Tet-loaded polycaprolactone-b-poly(ethylene glycol)-b-polycaprolactone nanoparticles (PTeNPs), is proposed to increase the potency of Tet against NSCLC. First, tetrandrine nanoparticles (TeNPs) are created using an emulsion solvent evaporation method, and biomimetic nanoparticles (PTeNPs) are prepared by coating the nanoparticles with PLTMs. When coated with PLTMs, PTeNPs are considerably less phagocytized by macrophages than Tet and TeNPs. In addition, compared with Tet and TeNPs, PTeNPs can significantly inhibit the growth and invasion of NSCLC both in vitro and in vivo. With reliable biosafety, this drug delivery system provides a new method of sustained release and efficient anticancer effects against NSCLC, facilitating the incorporation of Tet in modern nanotechnology.

Nitric oxide is involved in the regulation of guard mother cell division by inhibiting the synthesis of ACC.

A stoma forms by a series of asymmetric divisions of stomatal lineage precursor cell and the terminal division of a guard mother cell (GMC). GMC division is restricted to once through genetic regulation mechanisms. Here, we show that nitric oxide (NO) is involved in the regulation of the GMC division. NO donor treatment results in the formation of single guard cells (SGCs). SGCs are also produced in plants that accumulate high NO, whereas clustered guard cells (GCs) appear in plants with low NO accumulation. NO treatment promotes the formation of SGCs in the stomatal signalling mutants sdd1, epf1 epf2, tmm1, erl1 erl2 and er erl1 erl2, reduces the cell number per stomatal cluster in the fama-1 and flp1 myb88, but has no effect on stomatal of cdkb1;1 cyca2;234. Aminocyclopropane-1-carboxylic acid (ACC), a positive regulator of GMC division, reduces the NO-induced SGC formation. Further investigation found NO inhibits ACC synthesis by repressing the expression of several ACC SYNTHASE (ACS) genes, and in turn ACC represses NO accumulation by promoting the expression of HEMOGLOBIN 1 (HB1) encoding a NO scavenger. This work shows NO plays a role in the regulation of GMC division by modulating ACC accumulation in the Arabidopsis cotyledon.

The relationship between eHealth literacy and palliative care knowledge, attitudes, and practice among nurses: a cross-sectional study.

BACKGROUND: The crucial role that nurses play in offering palliative care to patients with life-threatening diseases is widely acknowledged, but the correlation between their eHealth literacy and their knowledge, attitudes, and practice in this domain has yet to be investigated. This study is conducted to investigate the status of eHealth literacy and knowledge, attitudes, and practice regarding palliative care among nurses, and to examine their relationship. METHODS: A cross-sectional study design was conducted among 546 nurses selected from the first-class tertiary hospitals located both inside and outside of Zhejiang Province between May 12 and May 20, 2022. The online survey of eHealth literacy scale (eHEALS) and scale of knowledge, attitudes, and practice (KAP) regarding palliative care was performed using snowball sampling through the WeChat mini program "Questionnaire Star". The Spearman rank correlation and binary logistic regression model were used to analyze the independent association between eHealth literacy and KAP toward palliative care. RESULTS: The median scores of eHEALS and KAP regarding palliative care were 32 (interquartile range[IQR] 29 to 38) and 82 (IQR 54 to 106) points. The results of correlation analysis showed that the KAP regarding palliative care was significantly correlated with eHEALS (rho = 0.189, P < 0.001). In addition, the results of binary logistic regression analysis demonstrated that the eHEALS score was independently associated with the KAP score regarding palliative care when controlling for sociodemographic factors (OR = 2.109; P < 0.001). CONCLUSION: Nurses who worked in first-class tertiary hospitals have good levels of eHealth literacy, while the overall level of KAP regarding palliative care is moderate. Our findings highlight that the eHEALS score is independently associated with the KAP score regarding palliative care. Therefore, nursing managers should adopt multiple measures to comprehensively improve eHealth literacy among nurses, further enrich their knowledge of palliative care, promote a positive transformation of attitudes towards palliative care, and efficiently implement palliative care practice, in order to promote high-quality development of palliative care.

Post-acute COVID-19 symptom risk in hospitalized and non-hospitalized COVID-19 survivors: A systematic review and meta-analysis.

Background: Post-acute coronavirus disease 2019 (COVID-19) symptoms occurred in most of the COVID-19 survivors. However, few studies have examined the issue of whether hospitalization results in different post-acute COVID-19 symptom risks. This study aimed to compare potential COVID-19 long-term effects in hospitalized and non-hospitalized COVID-19 survivors. Methods: This study is designed as a systematic review and meta-analysis of observational studies. A systematic search of six databases was performed for identifying articles published from inception until April 20th, 2022, which compared post-acute COVID-19 symptom risk in hospitalized and non-hospitalized COVID-19 survivors using a predesigned search strategy included terms for SARS-CoV-2 (eg, COVID, coronavirus, and 2019-nCoV), post-acute COVID-19 Syndrome (eg, post-COVID, post COVID conditions, chronic COVID symptom, long COVID, long COVID symptom, long-haul COVID, COVID sequelae, convalescence, and persistent COVID symptom), and hospitalization (hospitalized, in hospital, and home-isolated). The present meta-analysis was conducted according to The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 statement using R software 4.1.3 to create forest plots. Q statistics and the I 2 index were used to evaluate heterogeneity in this meta-analysis. Results: Six observational studies conducted in Spain, Austria, Switzerland, Canada, and the USA involving 419 hospitalized and 742 non-hospitalized COVID-19 survivors were included. The number of COVID-19 survivors in included studies ranged from 63 to 431, and follow-up data were collected through visits in four studies and another two used an electronic questionnaire, visit and telephone, respectively. Significant increase in the risks of long dyspnea (OR = 3.18, 95% CI = 1.90-5.32), anxiety (OR = 3.09, 95% CI = 1.47-6.47), myalgia (OR = 2.33, 95% CI = 1.02-5.33), and hair loss (OR = 2.76, 95% CI = 1.07-7.12) risk were found in hospitalized COVID-19 survivors compared with outpatients. Conversely, persisting ageusia risk was significantly reduced in hospitalized COVID-19 survivors than in non-hospitalized patients. Conclusion: The findings suggested that special attention and patient-centered rehabilitation service based on a needs survey should be provided for hospitalized COVID-19 survivors who experienced high post-acute COVID-19 symptoms risk.

Baicalin improved hepatic injury of NASH by regulating NRF2/HO-1/NRLP3 pathway.

Being at the important pathological stage and the critical treatment period of non-alcoholic fatty liver disease (NAFLD), nonalcoholic steatohepatitis (NASH) which is associated with fibrosis, hepatic and liver cancer has become a serious medical problem. As one of the major effective components in Scutellaria baicalensis, baicalin takes on anti-oxidant and anti-inflammatory activities. Nevertheless, its effects on NASH and its underlying molecular mechanism have not been thoroughly understood yet. In previous study, we have clarified baicalin could inhibit pyroptosis of hepatocytes mediated by NLRP3 in vitro, but the verification in vivo and upstream mechanism still need further work. Here the NASH mouse model was induced by feeding with a high fat diet (HFD) for 8-12 weeks. Thereafter, in the following weeks, NASH mice were given with HFD plus baicalin. We, subsequently, examined their hepatic function and inflammatory response and conducted the HE staining of liver samples. Furthermore, the underlying molecular mechanism was revealed through diverse molecular biological experiments including quantitative real-time PCR (qRT-PCR), Western blotting (WB), siRNA and CCK8 assays in HepG2 cells incubated with free fatty acid, and was verified in NASH mice. The in vivo findings indicated that baicalin decreased lipid accumulation and inflammation in the liver tissues of NASH mice, as evidenced by the enhanced NRF2/HO-1 expression and the reduced NLRP3/Caspase1/GSDMD levels, and these factors were involved in the pyroptosis pathway. Meanwhile, baicalin also contributed greatly against oxidative injury. The anti-inflammatory effect of baicalin was confirmed by experiments in vitro. For another, knockdown of NRF2 obviously weakened the protective effects of baicalin and reduced the NLRP3/Caspase1/GSDMD-mediated pyroptosis. This study indicates that baicalin is able to attenuate hepatic cell pyroptosis in vivo and in vitro in the case of NASH by regulating the NRF2/HO-1/NRLP3 pathway.

Advances in the roles and mechanisms of lignans against Alzheimer's disease.

Background: Alzheimer's disease (AD) is a serious neurodegenerative disease associated with the memory and cognitive impairment. The occurrence of AD is due to the accumulation of amyloid ß-protein (Aß) plaques and neurofibrillary tangles (NFTs) in the brain tissue as well as the hyperphosphorylation of Tau protein in neurons, doing harm to the human health and even leading people to death. The development of neuroprotective drugs with small side effects and good efficacy is focused by scientists all over the world. Natural drugs extracted from herbs or plants have become the preferred resources for new candidate drugs. Lignans were reported to effectively protect nerve cells and alleviate memory impairment, suggesting that they might be a prosperous class of compounds in treating AD. Objective: To explore the roles and mechanisms of lignans in the treatment of neurological diseases, providing proofs for the development of lignans as novel anti-AD drugs. Methods: Relevant literature was extracted and retrieved from the databases including China National Knowledge Infrastructure (CNKI), Elsevier, Science Direct, PubMed, SpringerLink, and Web of Science, taking lignan, anti-inflammatory, antioxidant, apoptosis, nerve regeneration, nerve protection as keywords. The functions and mechanisms of lignans against AD were summerized. Results: Lignans were found to have the effects of regulating vascular disorders, anti-infection, anti-inflammation, anti-oxidation, anti-apoptosis, antagonizing NMDA receptor, suppressing AChE activity, improving gut microbiota, so as to strengthening nerve protection. Among them, dibenzocyclooctene lignans were most widely reported and might be the most prosperous category in the develpment of anti-AD drugs. Conclusion: Lignans displayed versatile roles and mechanisms in preventing the progression of AD in in vitro and in vivo models, supplying potential candidates for the treatment of nerrodegenerative diseases.

Vaccarin alleviates endothelial inflammatory injury in diabetes by mediating miR-570-3p/HDAC1 pathway.

Vaccarin is a flavonoid glycoside, which has a variety of pharmacological properties and plays a protective role in diabetes and its complications, but its mechanism is unclear. In this study, we aim to investigate whether histone deacetylase 1(HDAC1), a gene that plays a pivotal role in regulating eukaryotic gene expression, is the target of miR-570-3p in diabetic vascular endothelium, and the potential molecular mechanism of vaccarin regulating endothelial inflammatory injury through miR-570-3p/HDAC1 pathway. The HFD and streptozotocin (STZ) induced diabetes mice model, a classical type 2 diabetic model, was established. The aorta of diabetic mice displayed a decrease of miR-570-3p, the elevation of HDAC1, and inflammatory injury, which were alleviated by vaccarin. Next, we employed the role of vaccarin in regulating endothelial cells miR-570-3p and HDAC1 under hyperglycemia conditions in vitro. We discovered that overexpression of HDAC1 counteracted the inhibitory effect of vaccarin on inflammatory injury in human umbilical vein endothelial cells (HUVECs). Manipulation of miRNA levels in HUVECs was achieved by transfecting cells with miR-570-3p mimic and inhibitor. Overexpression of miR-570-3p could decrease the expression of downstream components of HDAC1 including TNF-α, IL-1ß, and malondialdehyde, while increasing GSH-Px activity in HUVECs under hyperglycemic conditions. Nevertheless, such phenomenon was completely reversed by miR-570-3p inhibitor, and administration of miR-570-3p inhibitor could block the inhibition of vaccarin on HDAC1 and inflammatory injury. Luciferase reporter assay confirmed the 3'- UTR of the HDAC1 gene was a direct target of miR-570-3p. In summary, our findings suggest that vaccarin alleviates endothelial inflammatory injury in diabetes by mediating miR-570-3p/HDAC1 pathway. Our study provides a new pathogenic link between deregulation of miRNA expression in the vascular endothelium of diabetes and inflammatory injury and provides new ideas, insights, and choices for the scope of application and medicinal value of vaccarin and some potential biomarkers or targets in diabetic endothelial dysfunction and vascular complications.

Preparation and characterization of vaccarin, hypaphorine and chitosan nanoparticles and their promoting effects on chronic wounds healing.

Chronic wounds have become an important factor hindering human health, affecting tens of millions of people worldwide, especially diabetic wounds. Based on the antibacterial properties of chitosan, the angiogenesis promoting effect of vaccarin (VAC) and the anti-inflammatory effect of hypaphorine (HYP), nanoparticles with high bioavailability were prepared. VAC, HYP and chitosan nanoparticles (VAC + HYP-NPS) were used to the treatment of chronic wounds. Transmission electron microscopy (TEM) images showed the nanoparticles were spherical. ZetaPALS showed the potential of nanoparticles were -12.8 ± 5.53 mV and the size were 166.8 ± 29.95 nm. Methyl thiazolyl tetrazolium (MTT) assay showed that VAC + HYP-NPS had no toxicity and the biocompatibility was satisfactory. In the treatment of chronic wounds in diabetic rats, VAC + HYP-NPS significantly promoted the re-epithelialization of chronic wounds and accelerated the healing of chronic wounds. In the process of chronic wounds healing, VAC + HYP-NPS played the antibacterial effect of chitosan, the angiogenic effect of VAC and the anti-inflammatory effect of HYP, and finally promoted the chronic wounds healing. Overall, the developed VAC + HYP-NPS have potential application in chronic wounds healing. In view of the complexity of the causes of chronic wounds, multi-target drug administration may be an effective way to treat chronic wounds.

Impact of minimal solid and micropapillary components on invasive lung adenocarcinoma recurrence.

BACKGROUND: The specific impacts of solid and micropapillary components on prognosis in lung adenocarcinoma remain unclear. Herein, we elucidated their distinct contributions to lung adenocarcinoma recurrence. MATERIALS AND METHODS: Lung adenocarcinoma was classified into solid and micropapillary absent (S-M-); solid absent, micropapillary present (S-M+); micropapillary absent, solid present (S + M-); and solid and micropapillary present (S + M+). Cumulative incidence of recurrence (CIR) was calculated using competing risk analysis. RESULTS: Of 994 adenocarcinomas, 650 (65.4%) were classified as S-M-; 152 (15.3%), S-M+; 148 (14.9%), S + M-; and 44 (4.4%), S + M+. In total, 168 (16.9%) patients had recurrence; 16 (1.6%) died from other causes. S-M- had significantly lower CIR than other groups (S-M- vs. S-M+: P < 0.001, S-M- vs. S + M-: P < 0.001, S-M- vs. S + M+: P < 0.001); S + M- had significantly higher CIR than S-M+ (P = 0.002). These differences remained significant in multivariable analysis. In stage IA, S-M- had significantly lower CIR than other groups (S-M- vs. S-M+: P = 0.006, S-M- vs. S + M-: P < 0.001, S-M- vs. S + M+: P < 0.001); S + M- and S + M+ had significantly higher CIR than S-M+ (P = 0.005, P = 0.008, respectively). These differences remained significant in multivariable analysis. CIR was not significantly different between S + M- and S-M+ subgroups. CONCLUSIONS: The presence of solid or micropapillary component (≥1%) was an independent risk factor for CIR; patients with solid component alone had a higher CIR than those with micropapillary component alone. In IA lung adenocarcinoma, patients with both solid and micropapillary components had a higher CIR than those with micropapillary component alone; the proportion of solid or micropapillary component was not associated with CIR.

Study on Ultrasonic Imaging of Nursing Care for Preventing and Treating Clinical Infection of Hemodialysis Patients Based on Smart Medical Big Data.

The ultrasonic imaging research of nursing care for preventing and treating clinical infection of hemodialysis patients based on smart medical big data is studied. 100 hemodialysis patients were selected from May 2019 to May 2020. The patients were randomly divided into the observation group and routine group with 50 cases in each group. The PWV of common carotid artery was measured by ultrasonic rapid imaging technology, including BS value at the beginning of systole and ES value at the end of systole. According to the effect of preventive nursing intervention of intelligent medical treatment, the MHD group adopted preventive nursing intervention, while the routine group adopted traditional nursing service. The infection rate and quality of life score of patients in both groups were evaluated. The results showed that there were significant differences in BS and ES values between the MHD group and PWV in the normal group (P < 0.05). There was no significant difference in BS value and ES value between MHD patients with plaque and those without plaque (P > 0.05). It is proved that the ultrafast ultrasound imaging technology is safe, simple, noninvasive, nonradioactive, and fast and can automatically and accurately detect carotid PWV. It is expected to become a new imaging method for quantitative evaluation of arteriosclerosis degree in MHD patients. Preventive nursing intervention can reduce the incidence of infection in hemodialysis patients and improve their quality of life. Smart medical treatment has brought us a lot of convenience. As patients, we should change our concept, actively participate in it, and contribute to the development of smart medical treatment.

Effects of hydrogen as adjuvant treatment for unstable angina.

Oxidative stress and inflammation are closely related to atherosclerotic cardiovascular disease. It is established that hydrogen has significant protective effects on many diseases as a potential antioxidative and anti-inflammatory agent. The purpose of this study is to evaluate the effect of hydrogen on unstable angina in vitro and in vivo. An atherosclerosis model in vitro was constructed by ox-LDL-induced injury of human umbilical vein endothelial cells and in vitro testing indicated hydrogen inhibited ox-LDL-induced oxidative stress and inflammatory response by down-regulating LOX-1/NF-kB signaling pathway. Subsequently, the attenuating effect of hydrogen-rich water intake on unstable angina was further confirmed in clinic. Forty hospitalized subjects with unstable angina were enrolled and consumed either 1000-1200 mL/d hydrogen-rich water or the same amount of placebo pure water in addition to conventional drugs for three months. Clinical analysis showed hydrogen-rich water intake relieved angina symptoms in unstable angina patients. Serum analysis showed that hydrogen-rich water addition resulted in more effective reductions of total-cholesterol, low-density lipoprotein-cholesterol, and apolipoprotein B levels compared with conventional treatment. These results support that hydrogen as adjuvant treatment has a beneficial effect on unstable angina.

Metformin loaded porous particles with bio-microenvironment responsiveness for promoting tumor immunotherapy.

PD1/PD-L1 antibody blockade-based immunotherapy has been widely recognized in the field of cancer treatment; however, only a small number of cancer patients have been shown to respond well due to the PD1/PD-L1 antibody hydrolysis induced substandard immunotherapeutic efficacy and the low immunogenicity and immunosuppressive tumor microenvironment of the patients. Here, we present a novel tumor microenvironment (TME) responsive particle delivery system with a metformin-loaded chitosan (CS) inverse opal core and a manganese dioxide (MnO2) shell (denoted as CS-metformin@MnO2 particles) for inhibiting the PD-1/PD-L1 signaling pathway and promoting tumor immunotherapy. Benefiting from the interconnected porous structure of the inverse opal, metformin can be easily extensively loaded into the CS particles. With the coating of the TME responsive MnO2 shells, the particle delivery system was imparted with an intelligent "trigger" to prevent premature leaking of the drug until it reaches the tumor tissue. We have demonstrated that CS-metformin@MnO2 particles were able to promote the apoptosis of tumor cells through immunotherapeutic means both in vivo and in vitro. Specifically, the viability of tumor cells in the drug carrier-treated group was nearly 20% less than in the untreated group. In addition, the CS particles could serve as scaffolds for the regeneration of normal tissues and promote post-surgical wound healing due to their biocompatibility and antibacterial ability. These results make CS-metformin@MnO2 particles an excellent delivery system in tumor immunotherapy and post-surgical wound healing applications.