Gypenoside LXXV Alleviates Colitis by Reprograming Macrophage Polarization via the Glucocorticoid Receptor Pathway.

An imbalance in the macrophage phenotype is closely related to various inflammatory diseases. Here, we discovered that gypenoside LXXV (GP-75), a type of saponin from Gynostemma pentaphyllum, can reprogram M1-like macrophages into M2-like ones. On a mechanistic level, GP-75 inhibits NF-κB-COX2 signaling by targeting the glucocorticoid receptor (GR). Administration of GP-75, either orally or by intraperitoneal injection, significantly alleviates ulcerative colitis in mice, a pathogenesis associated with macrophage polarization. Clodronate liposomes, which deplete macrophages in mice, as well as GR antagonist RU486, abrogate the anticolitis effect of GP-75, thus confirming the pivotal role of macrophages in GP-75 function. We also showed that GP-75 has no toxicity in mice. Overall, this is the first report that demonstrates the effect of GP-75 on macrophage reprograming and as an agent against colitis. Because G. pentaphyllum is gaining popularity as a functional food, our findings offer new perspectives on the use of gypenosides as potential nutraceuticals for medical purposes.

Deficient RPE mitochondrial energetics leads to subretinal fibrosis in age-related neovascular macular degeneration.

Subretinal fibrosis permanently impairs the vision of patients with neovascular age-related macular degeneration. Despite emerging evidence revealing the association between disturbed metabolism in retinal pigment epithelium (RPE) and subretinal fibrosis, the underlying mechanism remains unclear. In the present study, single-cell RNA sequencing revealed, prior to subretinal fibrosis, genes in mitochondrial fatty acid oxidation are downregulated in the RPE lacking very low-density lipoprotein receptor (VLDLR), especially the rate-limiting enzyme carnitine palmitoyltransferase 1A (CPT1A). We found that overexpression of CPT1A in the RPE of Vldlr-/- mice suppresses epithelial-to-mesenchymal transition and fibrosis. Mechanistically, TGFß2 induces fibrosis by activating a Warburg-like effect, i.e. increased glycolysis and decreased mitochondrial respiration through ERK-dependent CPT1A degradation. Moreover, VLDLR blocks the formation of the TGFß receptor I/II complex by interacting with unglycosylated TGFß receptor II. In conclusion, VLDLR suppresses fibrosis by attenuating TGFß2-induced metabolic reprogramming, and CPT1A is a potential target for treating subretinal fibrosis.

Urban residential greenness and cancer mortality: Evaluating the causal mediation role of air pollution in a large cohort.

Evidence linking greenness to all-site and site-specific cancers remains limited, and the complex role of air pollution in this pathway is unclear. We aimed to fill these gaps by using a large cohort in southern China. A total of 654,115 individuals were recruited from 2009 to 2015 and followed-up until December 2020. We calculated the normalized difference vegetation index (NDVI) in a 500-m buffer around the participants' residences to represent the greenness exposure. Cox proportional-hazards models were used to evaluate the impact of greenness on the risk of all-site and site-specific cancer mortality. Additionally, we assessed both the mediation and interaction roles of air pollution (i.e., PM2.5, PM10, and NO2) in the greenness-cancer association through a causal mediation analysis using a four-way decomposition method. Among the 577,643 participants, 10,088 cancer deaths were recorded. We found a 10% (95% CI: 5-16%) reduction in all-site cancer mortality when the NDVI increased from the lowest to the highest quartile. When stratified by cancer type, our estimates suggested 18% (95% CI: 8-27%) and 51% (95% CI: 16-71%) reductions in mortality due to respiratory system cancer and brain and nervous system cancer, respectively. For the above protective effect, a large proportion could be explained by the mediation (all-site cancer: 1.0-27.7%; respiratory system cancer: 1.2-32.3%; brain and nervous system cancer: 3.6-109.1%) and negative interaction (all-site cancer: 2.1-25.7%; respiratory system cancer: 2.0-25.7%; brain and nervous system cancer: not significant) effects of air pollution. We found that particulate matter (i.e., PM2.5 and PM10) had a stronger causal mediation effect (25.0-109.1%) than NO2 (1.0-3.6%), while NO2 had a stronger interaction effect (25.7%) than particulate matter (2.0-2.8%). In summary, greenness was significantly beneficial in reducing the mortality of all-site, respiratory system, and brain and nervous system cancer in southern China, with the impact being modulated and mediated by air pollution.

The effect of residential greenness on cardiovascular mortality from a large cohort in South China: An in-depth analysis of effect modification by multiple demographic and lifestyle characteristics.

BACKGROUND: The potential for residential greenness to improve cardiovascular health through both physical and psychological mechanisms is well recognized. However, evidence from rapidly urbanizing developing countries and cohort-based causal inference approaches, remains limited. We aim to examine the effect of residential greenness and time to cardiovascular mortality in South China. METHODS: We utilized data from a community-based population survey involving 748,209 participants at baseline from 2009 to 2015, followed up until 2020. Residential greenness exposure was assessed by the annual Normalized Difference Vegetation Index (NDVI) in the 500 m radius of each participant's residence. We used time-varying proportional hazard Cox models coupled with inverse probability weighting to fit marginal structural models and obtain hazard ratios (HRs) for cardiovascular disease (CVD) mortality after adjusting for confounders. Multiple effect modifiers on both additive and multiplicative scales were further explored. RESULTS: A total of 15,139 CVD-related deaths were identified during a median of 7.9 years of follow-up. A protective effect was found between higher greenness exposure and reduced CVD mortality, with a 9.3 % lower rate of total CVD mortality (HR 0.907, 95 % CI 0.859-0.957) based on a 0.1 increase in annual average NDVI. Demographic (age, marital status) and lifestyle factors (smoking, drinking status) were found to modify the association between residential greenness and CVD mortality (all P interaction values < 0.05 or 95 %CI for RERI excluded the value 0). Notably, this effect was more pronounced among older adults, married, and individuals having healthier lifestyles, indicating a greater benefit from greenness for these subgroups. CONCLUSIONS: Our findings support a causal link between increased residential greenness exposure and a reduced risk of CVD mortality in South China with marked heterogenous effects, which has public health implications for cultivating greener urban environments to mitigate the impact of CVD within the context of rapid urbanization.

Invasive Fusarium solani infection diagnosed by traditional microbial detection methods and metagenomic next-generation sequencing in a pediatric patient: a case report and literature review.

Fusarium solani, as an opportunistic pathogen, can infect individuals with immunosuppression, neutropenia, hematopoietic stem cell transplantation (HSCT), or other high-risk factors, leading to invasive or localized infections. Particularly in patients following allogeneic HSCT, Fusarium solani is more likely to cause invasive or disseminated infections. This study focuses on a pediatric patient who underwent HSCT for severe aplastic anemia. Although initial blood cultures were negative, an abnormality was detected in the 1,3-ß-D-glucan test (G test) post-transplantation. To determine the causative agent, blood samples were subjected to metagenomic next-generation sequencing (mNGS) and blood cultures simultaneously. Surprisingly, the results of matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) and mNGS differed slightly, with mNGS identifying Nectria haematonectria, while MALDI-TOF MS based on culture showed Fusarium solani. To clarify the results, Sanger sequencing was performed for further detection, and the results were consistent with those of MALDI-TOF MS. Since the accuracy of Sanger sequencing is higher than that of mNGS, the diagnosis was revised to invasive Fusarium solani infection. With advancements in technology, various detection methods for invasive fungi have been developed in recent years, such as mNGS, which has high sensitivity. While traditional methods may be time-consuming, they are important due to their high specificity. Therefore, in clinical practice, it is essential to utilize both traditional and novel detection methods in a complementary manner to enhance the diagnosis of invasive fungal infections.

How long-term PM exposure may affect all-site cancer mortality: Evidence from a large cohort in southern China.

BACKGROUND: Evidence of a potential causal link between long-term exposure to particulate matter (PM) and all-site cancer mortality from large population cohorts remained limited and suffered from residual confounding issues with traditional statistical methods. AIMS: We aimed to examine the potential causal relationship between long-term PM exposure and all-site cancer mortality in South China using causal inference methods. METHODS: We used a cohort in southern China that recruited 580,757 participants from 2009 through 2015 and tracked until 2020. Annual averages of PM1, PM2.5, and PM10 concentrations were generated with validated spatiotemporal models. We employed a causal inference approach, the Marginal Structural Cox model, based on observational data to evaluate the association between long-term exposure to PM and all-site cancer mortality. RESULTS: With an increase of 1 µg/m³ in PM1, PM2.5, and PM10, the hazard ratios (HRs) and 95% confidence interval (CI) for all-site cancer were 1.033 (95% CI: 1.025-1.041), 1.032 (95% CI: 1.027-1.038), and 1.020 (95% CI: 1.016-1.025), respectively. The HRs (95% CI) for digestive system and respiratory system cancer mortality associated with each 1 µg/m³ increase in PM1 were 1.022 (1.009-1.035) and 1.053 (1.038-1.068), respectively. In addition, inactive participants, who never smoked, or who lived in areas of low surrounding greenness were more susceptible to the effects of PM exposure, the HRs (95% CI) for all-site cancer mortality were 1.042 (1.031-1.053), 1.041 (1.032-1.050), and 1.0473 (1.025-1.070) for every 1 µg/m³ increase in PM1, respectively. The effect of PM1 tended to be more pronounced in the low-exposure group than in the general population, and multiple sensitivity analyses confirmed the robustness of the results. CONCLUSION: This study provided evidence that long-term exposure to PM may elevate the risk of all-site cancer mortality, emphasizing the potential health benefits of improving air quality for cancer prevention.

CYR61 Acts as an Intracellular Microtubule-Associated Protein and Coordinates Mitotic Progression via PLK1-FBW7 Pathway.

Cysteine-rich angiogenic inducer 61 (CYR61), also called CCN1, has long been characterized as a secretory protein. Nevertheless, the intracellular function of CYR61 remains unclear. Here, we found that CYR61 is important for proper cell cycle progression. Specifically, CYR61 interacts with microtubules and promotes microtubule polymerization to ensure mitotic entry. Moreover, CYR61 interacts with PLK1 and accumulates during the mitotic process, followed by degradation as mitosis concludes. The proteolysis of CYR61 requires the PLK1 kinase activity, which directly phosphorylates two conserved motifs on CYR61, enhancing its interaction with the SCF E3 complex subunit FBW7 and mediating its degradation by the proteasome. Mutations of phosphorylation sites of Ser167 and Ser188 greatly increase CYR61's stability, while deletion of CYR61 extends prophase and metaphase and delays anaphase onset. In summary, our findings highlight the precise control of the intracellular CYR61 by the PLK1-FBW7 pathway, accentuating its significance as a microtubule-associated protein during mitotic progression.

Quantitative assessment of the associations between DNA repair gene XRCC3 Thr241Met polymorphism and pancreatic cancer.

BACKGROUND: Prior research exploring the correlation between the XRCC3 Thr241Met polymorphism and the susceptibility to pancreatic cancer has yielded conflicting outcomes. To date, there has been a notable absence of studies examining this polymorphism. The primary aim of the current investigation is to elucidate the potential role of the XRCC3 Thr241Met polymorphism as a risk factor in the development of pancreatic cancer. METHODS: The comprehensive literature search was meticulously conducted across primary databases, including PubMed, Embase, and CNKI (China National Knowledge Infrastructure), spanning from the inception of each database through January 2024. To synthesize the data, a meta-analysis was performed using either a fixed or random-effects model, as appropriate, to calculate the odds ratios (ORs) and their corresponding 95% confidence intervals (CIs). RESULTS: The analysis revealed significant associations between the XRCC3 Thr241Met polymorphism and an increased risk of pancreatic cancer. This was evidenced through various genetic model comparisons: allele contrast (T vs. C: OR = 0.77, 95% CI = 0.70-0.86, P < 0.001), homozygote comparison (TT vs. CC: OR = 0.71, 95% CI = 0.58-0.88, P = 0.001), heterozygote comparison (TC vs. CC: OR = 0.67, 95% CI = 0.52-0.87, P = 0.003), and a dominant genetic model (TT/TC vs. CC: OR = 0.68, 95% CI = 0.57-0.81, P < 0.001). Additionally, subgroup analyses based on ethnicity disclosed that these associations were particularly pronounced in the Caucasian population, with all genetic models showing significance (P < 0.05). CONCLUSIONS: The XRCC3 Thr241Met polymorphism has been identified as contributing to a reduced risk of pancreatic cancer in the Caucasian population. This finding underscores the need for further research to validate and expand upon our conclusions, emphasizing the urgency for continued investigations in this domain.

CAR T Cell Membrane Camouflaged Nanocatalyst Augments CAR T Cell Therapy Efficacy Against Solid Tumor.

The immunosuppressive tumor microenvironment (TME) reduces the chimeric antigen receptor (CAR) T-cell therapy against solid tumors. Here, a CAR T cell membrane-camouflaged nanocatalyst (ACSP@TCM) is prepared to augment CAR T cell therapy efficacy against solid tumors. ACSP@TCM is prepared by encapsulating core/shell Au/Cu2- xSe and 3-bromopyruvate with a CAR T cell membrane. It is demonstrated that the CAR T cell membrane camouflaging has much better-targeting effect than the homologous tumors cell membrane camouflaging. ACSP@TCM has an appealing synergistic chemodynamic/photothermal therapy (CDT/PTT) effect that can induce the immunogenic cell death (ICD) of NALM 6 cells. Moreover, 3-bromopyruvate can inhibit the efflux of lactic acid by inhibiting the glycolysis process, regulating the acidity of TME, and providing a more favorable environment for the survival of CAR T cells. In addition, the photoacoustic (PA) imaging and computed tomography (CT) imaging performance can guide the ACSP@TCM-mediated tumor therapy. The results demonstrated that the ACSP@TCM significantly enhanced the CAR T cell therapy efficacy against NALM 6 solid tumor mass, and completely eliminated tumors. This work provides an effective tumor strategy for CAR T cell therapy in solid tumors.

Classification of the relationship between suprasellar arachnoid cyst and hydrocephalus based on treatment modalities: shunting versus neuroendoscopic approaches.

PURPOSE: Children diagnosed with suprasellar arachnoid cysts often concurrently have hydrocephalus. This study aims to classify the relationship between suprasellar arachnoid cysts and hydrocephalus, discussing surgical strategies-shunting or neuroendoscopic approaches-and their sequence, based on this classification. METHODS: A retrospective analysis was conducted on 14 patients diagnosed with suprasellar arachnoid cysts and hydrocephalus, treated surgically by the first author between January 2016 and December 2020. Clinical features, radiological findings, surgical strategies, and outcomes were reviewed. The classification of the relationship between the suprasellar arachnoid cysts and hydrocephalus was developed and illustrated with specific cases. Recommendations for future surgical management based on this classification are provided. RESULTS: We classified the relationship between suprasellar arachnoid cysts and hydrocephalus into three categories. SACH-R1, the direct type, represents cases where the cysts cause obstructive hydrocephalus. Here, neuroendoscopic ventriculocystocisternostomy (VCC) effectively treats both conditions. SACH-R2, the juxtaposed type, involves concurrent occurrences of cysts and hydrocephalus without a causative link. This is further subdivided into SACH-R2a, where acute progressive communicating hydrocephalus coexists with the cyst, initially managed with a ventriculoperitoneal shunt, followed by VCC upon stabilization of hydrocephalus; and SACH-R2b, where the cyst coexists with chronic stable communicating hydrocephalus, first addressed with VCC, followed by monitoring and potential secondary shunting if needed. Key factors differentiating SACH-R2a from SACH-R2b include the patient's age, imaging signs of fourth ventricle and cisterna magna enlargement, and the rapid progression or chronic stability and severity of hydrocephalus symptoms. SACH-R3, the reverse type, describes scenarios where shunting for hydrocephalus leads to the development or enlargement of the cyst, managed via neuroendoscopic VCC with precautions to prevent infections in existing shunt systems. CONCLUSION: The simultaneous presence of suprasellar arachnoid cysts and hydrocephalus requires a nuanced understanding of their complex relationship for optimal surgical intervention. The analysis and classification of their relationship are crucial for determining appropriate surgical approaches, including the choice and sequence of shunting and neuroendoscopic techniques. Treatment should be tailored to the specific type identified, rather than blindly opting for neuroendoscopy. Particularly for SACH-R2a cases, we recommend initial ventriculoperitoneal shunting.

Smoking affects symptom improvement in schizophrenia: a prospective longitudinal study of male patients with first-episode schizophrenia.

Patients with schizophrenia (SCZ) smoke up to three times more than general people. However, there are conflicting results regarding the relationship between tobacco smoke and clinical symptom severity in SCZ. The aim of this study was to assess the impact of smoking on clinical symptoms after antipsychotic treatment in a 12-week cohort study after controlling for confounding factors. One hundred and forty-five male patients with drug-naïve first-episode (DNFE) SCZ received antipsychotic monotherapy for 12 weeks. Symptom severity was assessed at baseline and at week 12 by the Positive and Negative Syndrome Scale (PANSS). We found no differences in clinical symptoms among male smokers with SCZ compared with male nonsmokers. However, male smokers showed greater improvement in negative symptoms after 12 weeks of treatment, controlling for age, years of education, onset age, and baseline body mass index (BMI). Our study showed that after 12 weeks of treatment with antipsychotics, male smokers showed greater improvement in negative symptoms than male nonsmokers.

Golgi-targeting viscosity probe for the diagnosis of Alzheimer's disease.

Early diagnosis and intervention of Alzheimer's disease (AD) are particularly important to delay the pathological progression. Although fluorescent probes have been widely employed for investigating and diagnosing AD, their biological applications are significantly restricted due to the low penetration ability of the blood-brain barrier (BBB) in vivo. In this study, we reported the first Golgi-targeted two-photon (TP) fluorescent probe, DCM-DH, for detecting viscosity in the Golgi apparatus. The probe was rationally designed to exhibit superior analytical performance including high sensitivity, specific Golgi-targeting, efficient BBB penetration ability, and deep tissue penetration (247 µm) in the brains of AD model mice. Using the probe, we demonstrated that the fluorescence intensity in the human liver cancer cell (HepG2 cells) was higher than that of human normal liver cell (LO2 cells), and the brain viscosity of AD model mice increased significantly. We anticipate that this competent tool could be easily extended to other AD biomarkers for fundamental research on this detrimental disease.

Predictive Factors for Residual Low Back Pain Following Percutaneous Endoscopic Lumbar Discectomy in Patients with Lumbar Disc Herniation.

BACKGROUND Percutaneous endoscopic lumbar discectomy (PELD) is a mature and popular surgery for treatment of lumbar disc herniation (LDH). The main objective of our study was to identify risk factors for residual low back pain after PELD and to improve postoperative management. MATERIAL AND METHODS We retrospectively analyzed the clinical and imaging data of 251 patients who underwent PELD for LDH. We defined residual LBP as visual analog scale (VAS) score for LBP ≥3 at 2 years postoperatively, and severe LBP was defined as VAS for LBP ≥7.5. The clinical and imaging data were analyzed by comparing patients with VAS scores ≥3 and <3, and univariate analysis and multivariable logistic regression analysis were applied to predict the risk factors for residual LBP. RESULTS There were 56 (22.3%) patients with LBP VAS ≥3 at 2 years postoperatively. Multivariable logistic regression analysis demonstrated that severe baseline VAS for LBP (P<0.001), MCs type I (P=0.006), and severe fatty infiltration of the paravertebral muscles (P<0.001) were independent risk factors for residual LBP after PELD. CONCLUSIONS In patients with LDH, MCs type I, severe baseline LBP, and fatty infiltration of the paravertebral muscles were predictive factors for residual LBP after PELD. Our study suggests that spine surgeons should pay more attention to these imaging parameters, which may be a helpful indicator for the choice of surgical modality.

Potential causal links and mediation pathway between urban greenness and lung cancer mortality: Result from a large cohort (2009 to 2020).

Urban greenness, as a vital component of the urban environment, plays a critical role in mitigating the adverse effects of rapid urbanization and supporting urban sustainability. However, the causal links between urban greenness and lung cancer mortality and its potential causal pathway remain poorly understood. Based on a prospective community-based cohort with 581,785 adult participants in southern China, we applied a doubly robust Cox proportional hazard model to estimate the causal associations between urban greenness exposure and lung cancer mortality. A general multiple mediation analysis method was utilized to further assess the potential mediating roles of various factors including particulate matter (PM1, PM2.5-1, and PM10-2.5), temperature, physical activity, and body mass index (BMI). We observed that each interquartile range (IQR: 0.06) increment in greenness exposure was inversely associated with lung cancer mortality, with a hazard ratio (HR) of 0.89 (95 % CI: 0.83, 0.96). The relationship between greenness and lung cancer mortality might be partially mediated by particulate matter, temperature, and physical activity, yielding a total indirect effect of 0.826 (95 % CI: 0.769, 0.887) for each IQR increase in greenness exposure. Notably, the protective effect of greenness against lung cancer mortality could be achieved primarily by reducing the particulate matter concentration.

Immobilization of recombinant Trametes versicolor aflatoxin B1-degrading enzyme (TV-AFB1D) with montmorillonite for absorption and in situ degradation of aflatoxin B1.

Aflatoxin B1 is a highly carcinogenic and teratogenic substance mainly produced by toxin-producing strains such as Aspergillus flavus and Aspergillus parasitic. The efficient decomposition of aflatoxin is an important means to reduce its harm to humans and livestock. In this study, Trametes versicolor aflatoxin B1-degrading enzyme (TV-AFB1D) was recombinantly expressed in Bacillus subtilis (B. subtilis) 168. MMT-CTAB-AFB1D complex was prepared by the immobilization of TV-AFB1D and montmorillonite (MMT) by cross-linking glutaraldehyde. The results indicated that TV-AFB1D could recombinantly express in engineered B. subtilis 168 with a size of approximately 77 kDa. The immobilization efficiency of MMT-CTAB-AFB1D reached 98.63% when the concentration of glutaraldehyde was 5% (v/v). The relative activity of TV-AFB1D decreased to 72.36% after reusing for 10 times. The content of AFB1 in MMT-CTAB-AFB1D-AFB1 decreased to 1.1 µg/g from the initial 5.6 µg/g after incubation at 50 °C for 6 h. The amount of 80.4% AFB1 in the MMT-CTAB-AFB1D-AFB1 complex was degraded by in situ catalytic degradation. Thus, the strategy of combining adsorption and in situ degradation could effectively reduce the content of AFB1 residue in the MMT-CTAB-AFB1D complex.

The dePARylase NUDT16 promotes radiation resistance of cancer cells by blocking SETD3 for degradation via reversing its ADP-ribosylation.

Poly(ADP-ribosyl)ation (PARylation) is a critical posttranslational modification that plays a vital role in maintaining genomic stability via a variety of molecular mechanisms, including activation of replication stress and the DNA damage response. The nudix hydrolase NUDT16 was recently identified as a phosphodiesterase that is responsible for removing ADP-ribose units and that plays an important role in DNA repair. However, the roles of NUDT16 in coordinating replication stress and cell cycle progression remain elusive. Here, we report that SETD3, which is a member of the SET-domain containing protein (SETD) family, is a novel substrate for NUDT16, that its protein levels fluctuate during cell cycle progression, and that its stability is strictly regulated by NUDT16-mediated dePARylation. Moreover, our data indicated that the E3 ligase CHFR is responsible for the recognition and degradation of endogenous SETD3 in a PARP1-mediated PARylation-dependent manner. Mechanistically, we revealed that SETD3 associates with BRCA2 and promotes its recruitment to stalled replication fork and DNA damage sites upon replication stress or DNA double-strand breaks, respectively. Importantly, depletion of SETD3 in NUDT16-deficient cells did not further exacerbate DNA breaks or enhance the sensitivity of cancer cells to IR exposure, suggesting that the NUDT16-SETD3 pathway may play critical roles in the induction of tolerance to radiotherapy. Collectively, these data showed that NUDT16 functions as a key upstream regulator of SETD3 protein stability by reversing the ADP-ribosylation of SETD3, and NUDT16 participates in the resolution of replication stress and facilitates HR repair.

LincRNA-EPS inhibits caspase-11 and NLRP3 inflammasomes in gingival fibroblasts to alleviate periodontal inflammation.

To investigate the effects of long intergenic noncoding RNA-erythroid prosurvival (lincRNA-EPS) on periodontal inflammation mediated by inflammasomes and to explore its mechanism. Experimental periodontitis was induced in KO (lincRNA-EPS-/- ) and WT (lincRNA-EPS+/+ ) mice to compare the periodontal bone loss and inflammation by using micro-computed tomography, immunofluorescence staining and haematoxylin and eosin staining. The expression and activation of cysteinyl aspartate-specific proteinase-11 (caspase-11) and NOD-like receptor protein 3 (NLRP3) inflammasomes, as well as nuclear factor-kappa B (NF-κB) activation in mouse gingival fibroblasts (MGFs), were measured by real-time quantitative polymerase chain reaction, Western blotting, enzyme-linked immunosorbent and lactate dehydrogenase assays. MGFs were transfected with overexpression plasmids to assess the biological functions of lincRNA-EPS. RNA pull-down and immunoprecipitation experiments were performed to identify the interacting protein of lincRNA-EPS. LincRNA-EPS-expressing lentivirus was locally administered to inflamed periodontal tissues to evaluate its salvage function in periodontitis. The absence of lincRNA-EPS increased bone loss and expression of myeloperoxidase, interleukin-1α (IL-1α) and IL-1ß in the inflammatory periodontium. LincRNA-EPS KO MGFs exhibited increased expression and activation of caspase-11/NLRP3 inflammasome components than WT MGFs under lipopolysaccharide (LPS) stimulation. The expression and activation of these molecules were inhibited in lincRNA-EPS overexpressed MGFs. Mechanistically, lincRNA-EPS directly bound to transactive response DNA-binding protein 43 (TDP43) in the nucleus of MGFs, and TDP43 knockdown exerted a similar inhibitory effect on NF-κB activation and the inflammasomes as lincRNA-EPS overexpression. Locally injecting lincRNA-EPS-expressing lentivirus weakened the periodontal damage. LincRNA-EPS inhibits the LPS-induced production and activation of caspase-11 and NLRP3 inflammasomes by suppressing the activation of the NF-κB signalling pathway via interacting with TDP43, thereby alleviating periodontitis.

Effect of hydration therapy and nursing intervention on preventing contrast-induced nephropathy after interventional treatment of lower extremity arteriosclerosis obliterans.

BACKGROUND: Endoluminal interventions have become one of the main options for the treatment of arteriosclerosis obliterans (ASO). OBJECTIVE: To explore the effect of hydration therapy and nursing intervention on the prevention of contrast-induced nephropathy (CIN) after interventional treatment of lower extremity ASO. METHODS: A convenience sampling method was used to select 94 patients who received ASO treatment in our hospital from March 2019 to May 2021 as the study subjects. All patients underwent endovascular interventional therapy and were randomly divided into two groups by the random number table method, with odd numbers entering the observation group (n= 47) and even numbers entering the control group (n= 47). The control group received routine nursing intervention, while the observation group underwent hydration therapy and had a corresponding nursing intervention scheme. The clinical efficacy of the two groups and the incidence of contrast-induced nephropathy after interventional therapy were compared, and an evaluation of satisfaction within the two groups was performed via a questionnaire. RESULTS: The total effective rate of patients in the observation group was higher after hydration treatment (97.87% vs 87.23%, p< 0.05). The blood urea nitrogen, creatinine, and ß2 microglobulin levels in the observation group were significantly lower than those in the control group after the intervention (p< 0.05). Patients in the observation group had higher nursing satisfaction after using preventive measures of hydration therapy combined with nursing interventions (100% vs 89.36%, p< 0.05). CONCLUSION: Hydration therapy and nursing intervention can effectively prevent CIN after interventional treatment of lower extremity ASO. After interventional therapy, patients had better clinical outcomes, lower biochemical indexes and improved satisfaction evaluations. The therapy is worthy of clinical promotion and application.

The comparison of an accessible C-shaped partial stapled hemorrhoidopexy (C-PSH) versus circular stapled hemorrhoidopexy (CSH) in patients with grade IV hemorrhoids: a retrospective cohort study.

OBJECTIVES: The objectives of this study were to present an accessible C-shaped partial stapled hemorrhoidopexy (C-PSH) in the treatment of grade IV hemorrhoids and to assess long-term outcomes of this technique compared with circular stapled hemorrhoidopexy (CSH). METHODS: Conventional CSH kits combined with an intestinal spatula were used for performing C-PSH. A total of 256 patients with grade IV hemorrhoids referred to Hangzhou Third People's Hospital between January 2016 and June 2017 were obtained: 122 (47.7%) with C-PSH, and 134 (52.3%) with CSH. After propensity score matching, 222 patients (111 in C-PSH group and 111 in CSH group) were ultimately analyzed. The primary outcome was the five-year recurrence rate of hemorrhoids. Secondary outcomes included intraoperative outcomes, postoperative outcomes and complications. RESULTS: The operative time in the C-PSH group was slightly longer than that in the CSH group (p < 0.01). The vertical length of rectal mucosa specimen in the C-PSH group was shorter than that in the CSH group (p < 0.01). Compared with the CSH group, fecal urgency incidence and numeric rating scale (NRS) score at first defecation were lower in the C-PSH group (p < 0.05). Major complication rate in the CSH group was higher than that in the C-PSH group (p = 0.03). Five-year recurrence rate between the C-PSH group and CSH group was comparable (p > 0.05). Multivariate Cox regression analysis revealed that constipation was an independent prognostic factor for hemorrhoidal recurrence. CONCLUSIONS: The accessible C-PSH seems to be a safe and effective technique in managing grade IV hemorrhoids. It has advantages in alleviating postoperative pain at first defecation, fecal urgency and major complications compared with CSH. It could be an alternative technique in the treatment of grade IV hemorrhoids.

Predictive value of type D personality for cardiac events in Chinese patients with acute myocardial infarction.

BACKGROUND: Our study aimed to investigate the association between type D personality and adverse cardiac events in chinese patients after acute myocardial infarction (AMI). METHODS: Patients with AMI admitted to cardiac care unit (CCU) of China-Japan Friendship Hospital, Beijing, China between January 2016 and December 2017 were enrolled. 257 patients completed psychological questionnaires at enrollment. Type D personality was assessed with 14-item Type D Scale-14 (DS14). Anxiety and depression were quantified using Hospital Anxiety and Depression Scale (HADS). Multivariable logistic regression analysis was used to determine the independent predictors of in-hospital major adverse cardiac events (MACEs), while cox regression analysis was used to evaluate post-discharge endpoints. RESULTS: 54 patients (21%) were classified as Type D personality defined by the combination of a negative affectivity (NA) score ≥ 10 and a social inhibition (SI) score ≥ 10 on the DS14. Patients with Type D personality displayed significantly higher scores of anxiety (7.4 ± 3.1 vs. 4.2 ± 3.1, p < .001) and depression (7.2 ± 3.8 vs. 4.0 ± 3.4, p < .001). AMI patients with Type D personality had higher prevalence rates of anxiety (χ2 = 30.095, P < .001) and depression (χ2 = 27.082, P < .001). Type D group also displayed a significantly higher level of blood lipoprotein(a) (177.2 ± 200.7 vs. 118.1 ± 255.7 mg/L, P = .048). The incidence of in-hospital MACEs was higher in type D than in non-Type D patients (24.1% vs. 11.3%, χ2 = 5.751, P = .026). Multivariable logistic regression showed three significant independent predictors of in-hospital MACEs: age [odds ratio(OR) = 1.055; 95%CI 1.016-1.095, p = .004], type-D personality(OR 3.332; 95% CI 1.149-9.661, p = .014) and killip classification(OR 2.275, 95% CI 1.506-3.437, p < .001). The average follow-up time was 31 (23-37.5) months. Type D patients had higher incidences of post-discharge events(23.1% vs. 11.5%, p = .032). In the analysis of post-discharge events by Cox regression, χ2 of the Cox regression equation was 16.795 (P = .032). Smoking (HR 2.602; 95% CI1.266-5.347, p = .009) and type-D personality (HR 2.265; 95%CI 1.028-4.988, p = .042) were independent predictors of long-term cardiac events. Kaplan-Meier curves showed significant difference in event-free survival between type D and non-type D group (p = .043). CONCLUSIONS: Type D personality is an independent predictor of in-hospital and post-discharge cardiac events after AMI in Chinese patients.