Effectiveness and safety of vedolizumab and infliximab in biologic-naïve patients with moderate-to-severe ulcerative colitis: A multicenter, retrospective cohort study.

OBJECTIVES: We conducted this multicenter, retrospective cohort study aiming to evaluate the effectiveness and safety of vedolizumab (VDZ) and infliximab (IFX) in biologic-naïve patients with moderate-to-severe ulcerative colitis (UC). METHODS: Biologic-naïve patients with moderate-to-severe UC who were treated with IFX or VDZ for at least 14 weeks at three tertiary hospitals in southwest China between January 2021 and January 2023 were retrospectively included. Efficacy of the biologics was evaluated based on the steroid-free clinical remission rate, clinical remission rate, and mucosal healing rate at Weeks 14 and 52. Adverse events related to biologic use were recorded. RESULTS: Altogether 122 biologic-naïve patients with moderate-to-severe UC were included. No marked differences in the steroid-free clinical remission rate and clinical remission rate were observed between the two groups at Week 14 or Week 52 (P > 0.05). The VDZ group exhibited a higher mucosal healing rate at Week 14 compared to the IFX group (33.3% vs 16.9%, P = 0.036), while that at Week 52 did not differ between the two groups (65.6% vs 47.1%, P = 0.098). There was no statistically significant difference in the rate of adverse events between the two groups (P = 0.071). CONCLUSION: VDZ and IFX showed comparable clinical efficacy and safety profiles and can be used as viable first-line therapeutic options for biologic-naïve patients with moderate-to-severe UC.

Analysis of clinical characteristics of infections caused by shewanella species.

PURPOSE: The Shewanella genus is a rare pathogen of marine origin. In recent years, there has been a continuous increase in infection cases caused by this bacterium, and we have observed the uniqueness of infections caused by this microorganism. MATERIALS AND METHODS: This study conducted a retrospective analysis of the medical history and laboratory examination data of patients infected with the Shewanella genus over the past decade. Additionally, it employed bioinformatics methods to analyze the relevant virulence factors and antibiotic resistance genes associated with the Shewanella genus. RESULTS: Over the past 10 years, we have isolated 51 cases of Shewanella, with 68.82% being Shewanella putrefaciens (35/51 cases) and 31.37% being Shewanella algae (16/51 cases). Infected individuals often had underlying diseases, with 39.22% (20/51) having malignant tumors and 25.49% (13/51) having liver and biliary system diseases primarily characterized by stones. The majority of patients, 62.74% (32/51), exhibited mixed infections, including one case with a combination of infections from three other types of bacteria and five cases with a combination of infections from two other types of bacteria. The identified microorganisms were commonly resistant to ticarcillin-clavulanic acid (23.5%), followed by cefoperazone-sulbactam (19.6%), ciprofloxacin (17.6%), and cefotaxime (17.6%). Bioinformatics analysis indicates that Shewanella can express bile hydrolysis regulators and fatty acid metabolism regulators that aid in adapting to the unique environment of the biliary tract. Additionally, it expresses abundant catalase, superoxide dismutase, and two-component signal transduction system proteins, which may be related to environmental adaptation. Shewanella also expresses various antibiotic resistance genes, including beta-lactamases and aminoglycoside modification enzymes. Iron carriers may be one of its important virulence factors. CONCLUSIONS: We speculate that the Shewanella genus may exist as a specific colonizer in the human body, and under certain conditions, it may act as a pathogen, leading to biliary infections in the host.

Genus Shewanella: A Potential Intestinal Colonizer Associated With Post-Operative Surgical Site Infections in Coastal Regions.

Background: This study aims to elucidate the clinical characteristics of Shewanella-related surgical site infections (SSIs) and assess the risk of mortality in patients by establishing a predictive model. Patients and Methods: A retrospective analysis of medical history and laboratory data of Shewanella-related SSI patients over the past decade was conducted via the electronic medical record (EMR) system. A predictive model for mortality risk in Shewanella-related SSI patients was established using plasma interleukin-6 (IL-6) levels combined with the Howell-PIRO scoring system. Results: Over the past 10 years, 45 strains of Shewanella were isolated from specimens such as bile, drainage fluid, and whole blood in patients with digestive tract SSIs. Among them, 21 of 45 (46.67%) patients underwent malignant tumor resection of the digestive system, 14 of 45 (31.11%) underwent endoscopic retrograde cholangiopancreatography (ERCP) common bile duct exploration or the stone removal, and seven of 45 (15.56%) were trauma repair patients with fractures and abdominal injuries. Among the 45 Shewanella-related SSI patients, 10 died within 30 days of infection, six cases involved infections with more than two other types of bacteria. The combined use of IL-6 and Howell-PIRO scores for mortality risk assessment yielded an receiver operating characteristic (ROC) curve with an area under the curve (AUC) of 0.9350, a positive predictive value of 92.71%, a negative predictive value of 94.58%, a diagnostic sensitivity of 95.35%, and a diagnostic specificity of 92.14%-all higher than the model using IL-6 or Howell-PIRO scores alone. Conclusions: We found that residents in coastal areas faced an increased risk of Shewanella-related SSI. Moreover, the higher the number of concurrent microbial infections occurring alongside Shewanella-related SSI, the greater the mortality rate among patients. The combined application of plasma IL-6 levels and the Howell-PIRO scoring system is beneficial for assessing patient mortality risk and guiding timely and proactive clinical interventions.

Mrgprb2-mediated mast cell activation exacerbates Modic changes by regulating immune niches.

Modic changes are radiographic features associated with microfracture, low-virulence organism infection and chronic inflammation with inflammatory cell infiltration in the vertebral endplate region. Mast cells, as innate immune cells similar to macrophages, are present in painful degenerated intervertebral discs. However, the involvement and mechanisms of mast cells in the development of Modic changes remain unclear. Herein, we found increased mast cell infiltration in samples from patients with Modic changes and in mouse models of Modic changes. To clarify the role of mast cells in the progression of Modic changes, we used mast cell-deficient (KITW-SH/W-SH) mice to construct a model of Modic changes and found that the severity of Modic changes in KITW-SH/W-SH mice was significantly lower than that in WT mice. These findings were further supported by the use of a mast cell-specific activator (compound 48/80) and a stabilizer (cromolyn). Furthermore, we found that mast cells were not activated via the classic IgE pathway in the Modic change models and that Mrgprb2 is the specific receptor for mast cell activation reported in recent studies. Then, we utilized Mrgprb2 knockout mice to demonstrate that Mrgprb2 knockout inhibited mast cell activation and thus reduced the degree of Modic changes. Transcriptomic sequencing revealed aberrant PI3K-AKT and MAPK pathway activation in the Mrgprb2-deficient mast cells. Additionally, Mrgpbrb2-activated mast cells regulate immune niches by recruiting macrophages, promoting M1 polarization and reducing M2 polarization, thereby promoting the progression of Modic changes. These findings suggest that mast cells may serve as a novel therapeutic target for addressing Modic changes.

Forensic Identification and Evaluation of 25 Obstetric Brachial Plexus Palsy Medical Damage Cases.

OBJECTIVES: To analyze the high risk factors of obstetric brachial plexus palsy (OBPP), and to explore how to evaluate the relationship between fault medical behavior and OBPP in the process of medical damage forensic identification. METHODS: A retrospective analysis was carried out on 25 cases of medical damage liability disputes related to OBPP from 2017 to 2021 in Beijing Fayuan Judicial Science Evidence Appraisal Center. The shortcomings of hospitals in birth weight assessment, delivery mode selection, labor process observation and shoulder dystocia management, and the causal relationship between them and the damage consequences of the children were summarized. RESULTS: Fault medical behavior was assessed as the primary cause in 2 cases, equal cause in 10 cases, secondary cause in 8 cases, minor cause in 1 case, no causal relationship in 1 case, and unclear causal force in 3 cases. CONCLUSIONS: In the process of forensic identification of OBPP, whether medical behaviors fulfill diagnosis and treatment obligations should be objectively analyzed from the aspects of prenatal evaluation, delivery mode notification, standardized use of oxytocin, standard operation of shoulder dystocia, etc. Meanwhile, it is necessary to fully consider the objective risk of different risk factors and the difficulty of injury prevention, and comprehensively evaluate the causal force of fault medical behavior in the damage consequences.

Photocatalyzed Aerobic Cross-Dehydrogenative Coupling of Diarylphosphine Oxides with Alcohols and Phenols.

A photocatalytic cross-dehydrogenative coupling of diarylphosphine oxides with alcohols and phenols has been developed. Using organic dye Rose Bengal as the photocatalyst and air as the oxidant, the reaction proceeded smoothly at room temperature. Both alcohols and phenols were feasible, affording various organophosphinates in high yields. The absence of a halogenating reagent, the absence of a transition-metal catalyst, a green oxidant, and mild conditions make this strategy environmentally benign and sustainable. Mechanistic studies indicated that the reaction is enabled by the cooperation of photoredox catalysis and photosensitization.

Effects of initial corncob particle size on the short-term composting for preparation of cultivation substrates for Pleurotus ostreatus.

The short-term composting based on corncob for preparing Pleurotus ostreatus cultivation medium originated from agricultural production practices and so lacked systematic investigation. In this study, the influences of a Dafen (15 mm, DFT) and Xiaofen (5 mm, XFT) initial particle size (IPS) of corncob on the microbial succession and compost quality were examined. Results demonstrated that XFT compost was better suited for mushroom cultivation due to its high biological efficiency of 70 % and the absence of contamination. The composting microbes differed significantly between the DFT and XFT composts. During composting, the genera of Bacillus, Acinetobacter, Lactobacillus, Streptomyces, and Paenibacillus were majorly found in the DFT compost, while Acinetobacter, Lactobacillus, Puccinia, Bacteroides, and Bacillus genera dominated the XFT compost. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis showed that throughout the thermophilic phase, XFT compost had much greater relative abundances of sequences relevant to energy, carbohydrate, and amino acid metabolism than DFT compost. Analysis of network correlations and Mantel tests indicated that IPS reduction could increase microbial interactions. Overall, adjusting the IPS of corncob to 5 mm increased microbial interactions, improved compost quality, and thereby boosted the P. ostreatus yield. These findings will be pertinent in optimizing the composting process of cultivation medium for P. ostreatus.

Photoredox Catalytic Phosphine-Mediated Deoxygenative Hydroacylation of Azobenzenes with Carboxylic Acids.

The convenient and precise preparation of N,N'-diarylhydrazides, especially from readily available raw materials, remains highly challenging. Here, a photoredox catalytic phosphine-mediated deoxygenative hydroacylation of azobenzenes with abundant and readily available carboxylic acids has been developed. With Ir[dF(CF3)ppy]2(dtbbpy)PF6 as the photocatalyst, the reactions proceeded smoothly in the presence of PPh3 under visible light irradiation, delivering various N,N'-diarylhydrazides in up to 92% yields. Mechanistic studies revealed that the reaction proceeds via photoredox catalysis and phosphoranyl-radical-mediated C-O bond cleavage of carboxylic acids.

Induction of cervical disc degeneration and discogenic pain by low concentration Propionibacterium acnes infection: an in vivo animal study.

BACKGROUND: Although cervical intervertebral disc (IVD) degeneration is closely associated with neck pain, its cause remains unclear. In this study, an animal model of cervical disc degeneration and discogenic neck pain induced by a low concentration of Propionibacterium acnes (P. acnes-L) is investigated to explore the possible mechanisms of cervical discogenic pain. METHODS: Cervical IVD degeneration and discitis was induced in 8-week-old male rats in C3-C6 IVDs through the anterior intervertebral puncture with intradiscal injections of low and high concentrations of P. acnes (P. acnes-L, n = 20 and P. acnes-H, n = 15) or Staphylococcus aureus (S. aureus, n = 15), compared to control (injection with PBS, n = 20). The structural changes in the cervical IVD using micro-CT, histological evaluation, and gene expression assays after MRI scans at 2 and 6 weeks post-modeling. The P. acnes-L induced IVD degeneration model was assessed for cervical spine MRI, histological degeneration, pain-like behaviors (guarding behavior and forepaw von Frey), nerve fiber growth in the IVD endplate region, and DRG TNF-α and CGRP. RESULTS: IVD injection with P. acnes-L induced IVD degeneration with decreased IVD height and MRI T2 values. IVD injection with P. acnes-H and S. aureus both lead to discitis-like changes on T2-weighted MRI, trabecular bone remodeling on micro-CT, and osseous fusion after damage in the cartilage endplate adjacent to the injected IVD. Eventually, rats in the P. acnes-L group exhibited significant nociceptive hypersensitivity, nerve fiber ingrowth was observed in the IVD endplate region, inflammatory activity in the DRG was significantly increased compared to the control group, and the expression of the pain neurotransmitter CGRP was significantly upregulated. CONCLUSION: P. acnes-L was validated to induce cervical IVD degeneration and discogenic pain phenotype, while P. acnes-H induced was identified to resemble septic discitis comparable to those caused by S. aureus infection.

Developing a clinical-radiomic prediction model for 3-year cancer-specific survival in lung cancer patients treated with stereotactic body radiation therapy.

PURPOSE: The study aims to develop and validate a combined model for predicting 3-year cancer-specific survival (CSS) in lung cancer patients treated with stereotactic body radiation therapy (SBRT) by integrating clinical and radiomic parameters. METHODS: Clinical data and pre-treatment CT images were collected from 102 patients treated with lung SBRT. Multivariate logistic regression and the least absolute shrinkage and selection operator were used to determine the clinical and radiomic factors associated with 3-year CSS. Three prediction models were developed using clinical factors, radiomic factors, and a combination of both. The performance of the models was assessed using receiver operating characteristic curve and calibration curve. A nomogram was also created to visualize the 3-year CSS prediction. RESULTS: With a 36-month follow-up, 40 patients (39.2%) died of lung cancer and 62 patients (60.8%) survived. Three clinical factors, including gender, clinical stage, and lymphocyte ratio, along with three radiomic features, were found to be independent factors correlated with 3-year CSS. The area under the curve values for the clinical, radiomic, and combined model were 0.839 (95% CI 0.735-0.914), 0.886 (95% CI 0.790-0.948), and 0.914 (95% CI 0.825-0.966) in the training cohort, and 0.757 (95% CI 0.580-0.887), 0.818 (95% CI 0.648-0.929), and 0.843 (95% CI 0.677-0.944) in the validation cohort, respectively. Additionally, the calibration curve demonstrated good calibration performance and the nomogram created from the combined model showed potential for clinical utility. CONCLUSION: A clinical-radiomic model was developed to predict the 3-year CSS for lung cancer patients treated with SBRT.

Binding dynamics of cavity solitons in a Kerr resonator with high order dispersion.

Cavity solitons are persistent light pulses arising from the externally driven Kerr resonators. Thanks to the passive parametric gain, cavity soliton has been endowed with the natural advantage of the chip-scaled integration since it was first experimentally generated in the fiber-based platform. Deterministic single soliton with smooth spectrum is a preferred state for numerous applications. However, multiple solitons are more common in the resonators with anomalous dispersion. In this condition, adjacent solitons are easily perturbed to attract and collide with each other. Some experimental observations deviated from the aforementioned description have recorded the stable soliton intervals that can last for a long time scale. This phenomenon is known as soliton binding and is attributed to the presence of narrow resonant sidebands in the spectrum. While the stationary configuration of two binding solitons has been investigated, the dynamical evolution remains an area for further exploration. In this paper, we discuss the binding dynamics of the cavity solitons in the presence of high-order dispersion. The proposed theoretical predictions match well with the numerical results, encompassing both the stationary stable intervals and dynamic trajectories. Our research will provide a comprehensive insight into the soliton motion induced by the internal perturbations.

Influence of stone load on the outcome of same-session flexible ureteroscopy for bilateral upper urinary tract stones: a multicenter retrospective study.

Purpose: This study aimed to evaluate the efficacy and safety of same-session flexible ureteroscopy (fURS) for the treatment of bilateral upper urinary tract stones and to examine the influence of stone load on the outcome of same-session fURS, stratifying by total diameter of stones (TDS) ≤30 mm vs. >30 mm. Patients and methods: We retrospectively reviewed all cases of same-session fURS performed for bilateral upper urinary tract stones at four institutions between January 2017 and September 2020. All patients were divided into two groups based on TDS, ≤30 mm and >30 mm. Data on patient demographics, stone characteristics, surgical results, and complications were collected and analyzed for differences between the two groups. Stone-free rate (SFR) was defined as patients endoscopically stone-free or with radiological fragments <2 mm of each renal unit. Results: A total of 121 patients with bilateral upper urinary tract stones underwent same-session fURS, consisting of 73 patients in the TDS ≤ 30 mm group and 48 patients in the TDS > 30 mm group. The mean bilateral stone size was 28.2 ± 12.2 mm (range: 9.1-38.4 mm), with a mean operating time of 97.1 ± 39.6 min (range: 19-220 min). The SFR was 54.5% after the first fURS, and SFR increased to 97.5% after re-fURS for residual stones. The operation time for the TDS > 30 mm group was longer than that of the TDS ≤ 30 mm group (85.1 ± 36.5 vs. 115.4 ± 37.4 min, p < 0.001). The SFR after the first fURS was significantly lower in the TDS > 30 mm group than in the TDS ≤ 30 mm group (25.0% vs. 73.9%, p < 0.001). Although there was no statistically significant difference in overall SFR between the two groups (93.7% vs. 100%, p = 0.060), the rate of re-fURS for residual stones was higher in the TDS > 30 mm group than in the TDS ≤ 30 mm group (75% vs. 26%, p < 0.001). There were no significant differences in length of hospital stay (LOS) (2.2 ± 0.7 vs. 2.3 ± 1.0, p = 0.329) or complication rate (10.9% vs. 14.6%, p = 0.582) between the two groups. Conclusion: The results suggested that same-session fURS can be effectively performed with a low complication rate. A higher SFR after the first fURS can be achieved in the case of bilateral upper urinary tract stones with TDS ≤ 30 mm, and priority should be given to same-session fURS.

[Identification of Complex and Combined Antibody Consisted of Anti-c, Anti-E, Anti-Jka and Anti-Fya].

OBJECTIVE: To investigate the role of multiple serological methods in the identification of complex antibodies. METHODS: The blood group antigens were detected by saline and microcolumn agglutination methods. The saline method was used to screen and identify IgM-type antibodies in the patient's serum, while the polybrene, anti-globulin, microcolumn agglutination, enzymic and absorption-elution methods were used to screen and identify IgG-type antibodies. RESULTS: The patient was B/CCDee/Jk(a-b+)/Fy(a-b+) blood type. The serum reacted with panel cells, and the reaction presented anti-E pattern in the saline medium. It was fully positive in the microcolumn agglutination card, except 2 negative ones after using papain to treat the panel cells. Referring to the pattern table, it was concluded that there existed anti-c, anti-E, and anti-Jka antibodies, and one antibody corresponding to an antigen that was easily destroyed by papain. The red blood cells with specific phenotype were selected for absorption-elution to identify IgG-type anti-c, anti-E, anti-Jka and anti-Fya antibodies. CONCLUSION: It is confirmed that IgM-type anti-E, and IgG-type anti-c, anti-E, anti-Jka and anti-Fya antibodies exist in the patient's serum by multiple serological methods.

Spatial Transcriptomics of Aging Rat Ovaries Reveals Unexplored Cell Subpopulations with Reduced Antioxidative Defense.

INTRODUCTION: Ovarian aging is characterized by a gradual decline in quantity and quality of oocytes and lower chance of fertility. Better understanding the genetic modulation during ovarian aging can further address available treatment options for aging-related ovarian diseases and fertility preservation. METHODS: A novel technique spatial transcriptomics (ST) was used to investigate the spatial transcriptome features of rat ovaries. Transcriptomes from ST spots in the young and aged ovaries were clustered using differentially expressed genes. These data were analyzed to determine the spatial organization of age-induced heterogeneity and potential mechanisms underlying ovarian aging. RESULTS: In this study, ST technology was applied to profile the comprehensive spatial imaging in young and aged rat ovary. Fifteen ovarian cell clusters with distinct gene-expression signatures were identified. The gene expression dynamics of granulosa cell clusters revealed three sub-types with sequential developmental stages. Aged ovary showed a significant decrease in the number of granulosa cells from the antral follicle. Besides, a remarkable rearrangement of interstitial gland cells was detected in aging ovary. Further analysis of aging-associated transcriptional changes revealed that the disturbance of oxidative pathway was a crucial factor in ovarian aging. CONCLUSIONS: This study firstly described an aging-related spatial transcriptome changes in ovary and identified the potential targets for prevention of ovarian aging. These data may provide the basis for further investigations of the diagnosis and treatment of aging-related ovarian disorders.

The correlation of two bone turnover markers with bone mineral density: a population-based cross-sectional study.

OBJECTIVE: Exploring the correlation between bone turnover marks (BTMs) with lumbar BMD in middle-aged populations. METHODS: The cross-sectional analysis fetched data came from NHANES. The level of serum bone alkaline phosphatase (sBAP) and urinary N-telopeptide (uNTx) were regarded as representative of bone turnover. Lumbar BMD was the outcome of the study. Multivariable linear regression models were utilized to detect the correlation of sBAP and uNTx with Lumbar BMD. RESULTS: The level of sBAP and uNTx was negatively correlated with lumbar BMD in every multivariable linear regression. For sBAP, this inverse correlation was stable in both men and women (P < 0.01). uNTx indicated a negative association after all relevant covariables were adjusted (P < 0.01). The men group remained the negative correlation in gender subgroup analysis (P < 0.01). CONCLUSION: This study indicated that the increased level of sBAP and uNTx associated with lumbar BMD decreased among middle-aged adults. This correlation could prompt researchers to explore further the relationship between bone turnover rate and BMD, which may provide information for the early detection of BMD loss and provide a new strategy for clinical practice.

Light-Driven Electron Uptake from Nonfermentative Organic Matter to Expedite Nitrogen Dissimilation by Chemolithotrophic Anammox Consortia.

Nonphotosynthetic microorganisms are typically unable to directly utilize light energy, but light might change the metabolic pathway of these bacteria indirectly by forming intermediates such as reactive oxygen species (ROS). This work investigated the role of light on nitrogen conversion by anaerobic ammonium oxidation (anammox) consortia. The results showed that high intensity light (>20000 lx) caused ca. 50% inhibition of anammox activity, and total ROS reached 167% at 60,000 lx. Surprisingly, 200 lx light was found to induce unexpected promotion of the nitrogen conversion rate, and ultraviolet light (<420 nm) was identified as the main contributor. Metagenomic and metatranscriptomic analyses revealed that the gene encoding cytochrome c peroxidase was highly expressed only under 200 lx light. 15N isotope tracing, gene abundance quantification, and external H2O2 addition experiments showed that photoinduced trace H2O2 triggered cytochrome c peroxidase expression to take up electrons from extracellular nonfermentative organics to synthesize NADH and ATP, thereby expediting nitrogen dissimulation of anammox consortia. External supplying reduced humic acid into a low-intensity light exposure system would result in a maximal 1.7-fold increase in the nitrogen conversion rate. These interesting findings may provide insight into the niche differentiation and widespread nature of anammox bacteria in natural ecotopes.

Developing a Prediction Model for Radiation Pneumonitis in Lung Cancer Patients Treated With Stereotactic Body Radiation Therapy Combined With Clinical, Dosimetric Factors, and Laboratory Biomarkers.

BACKGROUND: The study aims to identify the risk factors and develop a model for predicting grade ≥2 radiation pneumonitis (RP) for lung cancer patients treated with stereotactic body radiation therapy (SBRT). MATERIALS AND METHODS: Clinical data, dosimetric data, and laboratory biomarkers from 186 patients treated with lung SBRT were collected. Univariate and multivariate logistic regression were performed to determine the predictive factors for grade ≥2 RP. Three models were developed by using the clinical, dosimetric, and combined factors, respectively. RESULTS: With a median follow-up of 36 months, grade ≥2 RP was recorded in 13.4% of patients. On univariate logistic regression analysis, clinical factors of age and lung volume, dosimetric factors of treatment durations, fractional dose and V10, and laboratory biomarkers of neutrophil, PLT, PLR, and Hb levels were significantly associated with grade ≥2 RP. However, on multivariate analysis, only age, lung volume, fractional dose, V10, and Hb levels were independent factors. AUC values for the clinical, dosimetric, and combined models were 0.730 (95% CI, 0.660-0.793), 0.711 (95% CI, 0.641-0.775) and 0.830 (95% CI, 0.768-0.881), respectively. The combined model provided superior discriminative ability than the clinical and dosimetric models (P < .05). CONCLUSION: Age, lung volume, fractional dose, V10, and Hb levels were demonstrated to be significant factors associated with grade ≥2 RP for lung cancer patients after SBRT. A novel model combining clinical, dosimetric factors, and laboratory biomarkers improved predictive performance compared with the clinical and dosimetric model alone.

Investigations of the distant metastatic non-small cell lung cancer without local lymph node involvement: Real world data from a large database.

INTRODUCTION: This study aimed to investigate the presentations and survival outcomes of the distant metastatic non-small cell lung cancer (NSCLC) without lymph node involvement to obtain a clearer picture of this special subgroup of metastatic NSCLC. METHOD: A least absolute shrinkage and selection operator (LASSO) penalized Cox regression analysis was used to select the prognostic variables. A nomogram and corresponding risk-classifying systems were constructed. The C-index and calibration curves were used to evaluate the performance of the model. Overall survival (OS) curves were plotted using the Kaplan-Meier method, and the log-rank test was used to compare OS differences between groups. Propensity score matching (PSM) was performed to reduce bias. RESULT: A total of 12 610 NSCLC patients with M1 category (N0 group: 3045 cases; N1-3 group: 9565 cases) were included. Regarding the N0 group, multivariate analysis demonstrated that age, sex, race, surgery, grade, tumor size, and M category were independent prognostic factors. A nomogram and corresponding risk-classifying systems were formulated. Favorable validation results were obtained from the C-index, calibration curves, and survival comparisons. Survival curves demonstrated that N0 NSCLC patients had better survival than N1-3 NSCLC patients both before and after PSM. Furthermore, the survival of resected N0M1 patients was superior to that of those without surgery. CONCLUSION: In this study, a prognostic nomogram and risk-classifying systems designed for the T1-4N0M1 NSCLC patients showed acceptable performance. Primary lung tumor resection might be a feasible treatment for this population subset. Additionally, we proposed that lymph node stage might have a place in the forthcoming tumor-node-metastasis (TNM) staging proposal for NSCLC patients with M1 category.

A Dual-Targeted Metal-Organic Framework Based Nanoplatform for the Treatment of Rheumatoid Arthritis by Restoring the Macrophage Niche.

Inflammatory infiltration and bone destruction are important pathological features of rheumatoid arthritis (RA), which originate from the disturbed niche of macrophages. Here, we identified a niche-disrupting process in RA: due to overactivation of complement, the barrier function of VSIg4+ lining macrophages is disrupted and mediates inflammatory infiltration within the joint, thereby activating excessive osteoclastogenesis and bone resorption. However, complement antagonists have poor biological applications due to superphysiologic dose requirements and inadequate effects on bone resorption. Therefore, we developed a dual-targeted therapeutic nanoplatform based on the MOF framework to achieve bone-targeted delivery of the complement inhibitor CRIg-CD59 and pH-responsive sustained release. The surface-mineralized zoledronic acid (ZA) of ZIF8@CRIg-CD59@HA@ZA targets the skeletal acidic microenvironment in RA, and the sustained release of CRIg-CD59 can recognize and prevent the complement membrane attack complex (MAC) from forming on the surface of healthy cells. Importantly, ZA can inhibit osteoclast-mediated bone resorption, and CRIg-CD59 can promote the repair of the VSIg4+ lining macrophage barrier to achieve sequential niche remodeling. This combination therapy is expected to treat RA by reversing the core pathological process, circumventing the pitfalls of traditional therapy.

The mortality risk after myocardial infraction in migrants compared with natives: a systematic review and meta-analysis.

Background and Objective: The evidence on the risk of mortality after myocardial infarction (MI) among migrants compared with natives is mixed and limited. The aim of this study is to assess the mortality risk after MI in migrants compared to natives. Methods: This study protocol is registered with PROSPERO, number CRD42022350876. We searched the Medline and Embase databases, without time and language constraints, for cohort studies that reported the risk of mortality after MI in migrants compared to natives. The migration status is confirmed by country of birth, both migrants and natives are general terms and are not restricted to a particular country or area of destination or origin. Two reviewers separately screened searched studies according to selection criteria, extracted data, and assessed data quality using the Newcastle-Ottawa Scale (NOS) and risk of bias of included studies. Pooled estimates of adjusted and unadjusted mortality after MI were calculated separately using a random-effects model, and subgroup analysis was performed by region of origin and follow-up time. Result: A total of 6 studies were enrolled, including 34,835 migrants and 284,629 natives. The pooled adjusted all-cause mortality of migrants after MI was higher than that of natives (OR, 1.24; 95% CI, 1.10-1.39; I2 = 83.1%), while the the pooled unadjusted mortality of migrants after MI was not significantly different from that of natives (OR, 1.11; 95% CI, 0.69-1.79; I2 = 99.3%). In subgroup analyses, adjusted 5-10 years mortality (3 studies) was higher in the migrant population (OR, 1.27; 95% CI, 1.12-1.45; I2 = 86.8%), while adjusted 30 days (4 studies) and 1-3 years (3 studies) mortality were not significantly different between the two groups. Migrants from Europe (4 studies) (OR, 1.34; 95% CI, 1.16-1.55; I2 = 39%), Africa (3 studies) (OR, 1.50; 95% CI, 01.31-1.72; I2 = 0%), and Latin America (2 studies) (OR, 1.44; 95% CI, 1.30-1.60; I2 = 0%) had significantly higher rates of post-MI mortality than natives, with the exception of migrants of Asian origin (4 studies) (OR, 1.20; 95% CI, 0.99-1.46; I2 = 72.7%). Conclusions: Migrants tend to have lower socioeconomic status, greater psychological stress, less social support, limited access to health care resources, etc., therefore, face a higher risk of mortality after MI in the long term compared to natives. Further research is needed to confirm our conclusions, and more attention should be paid to the cardiovascular health of migrants. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/, identifier: r CRD42022350876.