Significant spatiotemporal pattern of nitrous oxide emission and its influencing factors from a shallow eutropic lake in Inner Mongolia, China.

Eutrophic shallow lakes are generally considered as a contributor to the emission of nitrous oxide (N2O), while regional and global estimates have remained imprecise. This due to a lack of data and insufficient understanding of the multiple contributing factors. This study characterized the spatiotemporal variability in N2O concentrations and N2O diffusive fluxes and the contributing factors in Lake Wuliangsuhai, a typical shallow eutrophic and seasonally frozen lake in Inner Mongolia with cold and arid climate. Dissolved N2O concentrations of the lake exhibited a range of 4.5 to 101.2 nmol/L, displaying significant spatiotemporal variations. The lowest and highest concentrations were measured in summer and winter, respectively. The spatial distribution of N2O flux was consistent with that of N2O concentrations. Additionally, the hotspots of N2O emissions were detected within close to the main inflow of lake. The wide spatial and temporal variation in N2O emissions indicate the complexity and its relative importance of factors influencing emissions. N2O emissions in different lake zones and seasons were regulated by diverse factors. Factors influencing the spatial and temporal distribution of N2O concentrations and fluxes were identified as WT, WD, DO, Chl-a, SD and COD. Interestingly, the same factor demonstrated opposing effects on N2O emission in various seasons or zones. This research improves our understanding of N2O emissions in shallow eutrophic lakes in cold and arid areas.

A nickel porphyrin-based covalent organic framework modified electrode for the electrochemical detection of acetaminophen.

Covalent organic frameworks (COFs) can be rationally designed with functional organic ligands to improve the electrochemical responsiveness of the electrode toward certain medicinal compounds. In this study, we synthesized a COF-Ni electrocatalyst material, which is formed by covalent coupling of electron-rich 2,3,6,7-tetrakis (4-formylphenyl) tetrakis (4-imidazolyl) (TTF-4CHO) and hole-rich 5,10,15,20-tetrakis (4-aminophenyl) porphyrin nickel(II) (TAPP-Ni). The reasonable electron transfer path design, the large specific surface area of the COF and the physical properties of ordered nanopores, as well as the Ni-N4 bond as a highly active catalytic center, allow the COF-Ni material modified electrode to exhibit excellent sensing performance for acetaminophen (ACOP). The detection limit for ACOP is as low as 47.6 nM, with a linear range of 1-1500 µM, which is better than for most of the reported sensors. With superior interference resistance and good stability performance, COF-Ni is a highly suited electrode modification material for real-world sample detection, which provided a new perspective for application of COF materials in drug analysis.

Immunotherapy and pan-apoptotic characterization of the tumor microenvironment in gastric cancer (STAD): a single-cell multidimensional analysis.

BACKGROUND: The aim of this study was to elucidate the critical role of autophagy-related gene aggregation in gastric cancer tumor microenvironment cells and to investigate their major roles in cellular functions. In particular, the expression of these genes in tumor-associated fibroblast subtypes was scrutinized in an attempt to explain their cell-subpopulation-specific roles in cell-cell communication and regulation of cellular functions. METHODS: In this study, single-cell RNA sequencing data were first analyzed in multiple steps, including data preprocessing, cell clustering, and cell classification. Cell subpopulations and gene expression patterns were identified and analyzed using unsupervised non-negative matrix factorization (NMF) techniques. The dynamic expression of autophagy-related gene aggregates in various cell types was deciphered by pseudotime trajectory analysis (PTA). Intercellular communication analysis was performed using the CellChat R software package, revealing the intricate communication patterns and exchange of key signaling molecules between cell subpopulations, and SCENIC analysis was used to identify gene regulatory networks and reveal the mechanisms behind cellular heterogeneity. RESULT: Cell subpopulations associated with pan-apoptosis were identified by NMF decomposition and SCENIC analysis. Cell-cell communication analysis revealed intricate communication patterns and exchange of key signaling molecules between cell subpopulations. Dynamic expression of autophagy-related genes aggregated in the pseudotemporal trajectory of STAD was observed by PTA. In the fibroblast subtype, different ligand-receptor interactions and their key roles in immunomodulation were observed. CONCLUSION: By deeply analyzing and comparing gene expression patterns within cellular subpopulations and intercellular communication, this study provides new insights into the role of pan-apoptosis-related genes in regulating immune responses and cellular functions in gastric cancer. These findings pave the way for further exploration of the role of these genes in tumorigenesis and immune regulation, as well as laying the foundation for potential therapeutic strategies.

Designing High-Performance Nanoscale Spin-MOSFET Devices by Using Two-Dimensional Half-Metallic Cr2Se3.

Constructing nanoscale spin devices has been a crucial pursuit in the field of nano spintronics. Here, by using the density functional theory (DFT) and nonequilibrium Green's function (NEGF) method, high-performance nanoscale spin-MOSFET devices using half-metallic 2D Cr2Se3 as electrodes are theoretically designed. Specifically, seven typical two-dimensional (2D) semiconductors, Sb, Bi, BP, BAs, MoTe2, WTe2, and WSeTe (with two different contacting surfaces), are considered here as the channel materials. The properties of contact interfaces between these 2D semiconductors and half-metallic 2D Cr2Se3 are first investigated. It is found that except BP and BAs (having Schottky contacts with Cr2Se3), the other 2D semiconductors have vertical Ohmic contacts with Cr2Se3 among which Cr2Se3/Sb, Cr2Se3/MoTe2, Cr2Se3/WTe2, Cr2Se3/WSeTe-Se, and Cr2Se3/WSeTe-Te retain the half-metallic characteristic. Then, these 2D semiconductors with Ohmic vertical contacts are further used to construct spin-MOSFET devices. The results show that devices constructed by half-metallic vertical contacting systems have nearly 100% SIE and therefore giant MR (>107%) when the gate voltage varies. Furthermore, four designed spin-MOSFET devices, namely, Cr2Se3/MoTe2, Cr2Se3/WTe2, Cr2Se3/WSeTe-Se, and Cr2Se3/WSeTe-Te spin-MOSFET have high efficient gate modulations on the magnitude of completely spin-polarized source-drain current with Cr2Se3/WTe2 having the smallest SS value of 134.1 mV/dec. The calculations suggest that Cr2Se3 is a good candidate for constructing spin-MOSFET devices. Our study sheds light on the design of high-performance nanoscale spin-MOSFET devices by using two-dimensional half-metallic electrodes.

Anatomical and dosimetric variations during volumetric modulated arc therapy in patients with locally advanced nasopharyngeal carcinoma after induction therapy: Implications for adaptive radiation therapy.

Purpose: To investigate anatomical and dosimetric changes during volumetric modulated arc therapy (VMAT) in patients with locally advanced nasopharyngeal carcinoma (LA-NPC) after induction therapy (IT) and explore characteristics of patients with notable variations. Materials and methods: From July 2021 to June 2023, 60 LA-NPC patients undergoing VMAT after IT were retrospectively recruited. Adaptive computed tomography (aCT), reconstructed from weekly cone-beam computed tomography(CBCT), facilitates recontouring and planning transplantation. Volume, dice similarity coefficients, and dose to target volumes and organs at risk(OARs) on planning CT(pCT) and aCT were compared to identify changing patterns. Multivariate logistic regression was used to investigate risk factors. Results: The volumes of PGTVnasopharynx (PGTVp), PGTVnode (PGTVn), ipsilateral and contralateral parotid glands decreased during VMAT, with reductions of 2.25 %, 6.98 %, 20.09 % and 18.00 %, respectively, at 30 fractions from baseline (P < 0.001). After 25 fractions, D99 and D95 of PGTVn decreased by 7.94 % and 4.18 % from baseline, respectively, while the Dmean of ipsilateral and contralateral parotid glands increased by 7.80 % and 6.50 %, marking the peak rates of dosimetric variations (P < 0.001). The dosimetric fluctuations in PGTVp, the brainstem, and the spinal cord remained within acceptable limits. Furthermore, an initial BMI ≥ 23.5 kg/m2 and not-achieving objective response (OR) after IT were regarded as risk factors for a remarkable PGTVn dose reduction in the later stages of VMAT. Conclusions: Replanning for post-IT LA-NPC patients appears reasonable at 25F during VMAT. Patients with an initial BMI ≥ 23.5 kg/m2 and not-achieving OR after IT should be considered for adaptive radiation therapy to stabilize the delivered dose.

Gastric cancer liver metastasis will reduce the efficacy of immunotherapy.

Immune checkpoint inhibitors augment the antitumor activity of T cells by inhibiting the negative regulatory pathway of T cells, leading to notable efficacy in patients with non-small cell lung cancer, melanoma, and other malignancies through immunotherapy utilization. However, secondary malignant liver tumors not only lower the liver's sensitivity to immunotherapy but also trigger systemic immune suppression, resulting in reduced overall effectiveness of immune therapy. Patients receiving immunotherapy for non-small cell lung cancer and melanoma experience reduced response rates, progression-free survival, and overall survival when secondary malignant tumors develop in the liver. Through Liu's retrospective analysis, valuable insights are provided for the future clinical management of these patients. Therefore, in patients with gastric cancer (GC), the occurrence of liver metastasis might be indicative of reduced efficacy of immunotherapy. Overcoming liver immune tolerance mechanisms and their negative impacts allows for the potential benefits of immunotherapy in patients with GC and liver metastasis.

Anteromedial cortical support reduction of intertrochanteric fractures-A review.

The intertrochanteric fracture is a common fragility fracture typically resulting from low-energy falls. The functional outcome of intertrochanteric fractures is closely linked to the patient's underlying physical condition, intraoperative procedures, and postoperative complications. In terms of surgery, while timely surgery and appropriate internal fixation have demonstrated favorable outcomes, attention to intraoperative reduction is crucial. In recent years, there have been further developments in the evaluation of reduction of intertrochanteric fractures, particularly in the anteromedial cortical reduction, and these advances have been further scientifically elucidated in terms of their ability to provide stable fracture reduction and resist loss of reduction. In order to gain a comprehensive understanding of the anteromedial cortex theory, this article reviewed the anatomy, related theoretical progress, and controversies in recent years.

Introducing palmfungi.org, an integrated fungal-host data platform.

Palm fungi are a diverse and unique group mostly found on Arecaceae hosts. They have been studied for approximately 200 years resulting in a large number of known fungal species representing over 700 genera. The timeline of palm fungal studies could be roughly divided into three phases, based on the methods and frequency of reports. They are the "Historical palm fungi era", "Classical palm fungi era" and "Molecular palm fungi era". In the first two periods, the identification of palm fungi was based on morphology, which resulted in a considerable number of morphological species scattered across the data in books, monographs and papers. With the advancement of molecular techniques, studies on palm fungi accelerated. A large number of new species were introduced in the molecular era, especially from Asia, including China and Thailand. However, there is a necessity to link these three generations of studies into a single platform combining data related to host factors, geography and utilisation. Herein, we introduce the palm fungi website: https://palmfungi.org, an integrated data platform for interactive retrieval, based on palm and fungal species. This website is not only a portal for the latest, comprehensive species information on palm fungi, but also provides a new platform for fungal researchers to explore the host-specificity of palm fungi. Additionally, this study uses palmfungi.org and related data to briefly discuss the current status of research on the distribution of palm fungi populations, showing how palmfungi.org links fungi with their palm hosts. Furthermore, the website will act as a platform for collaboration amongst taxonomists, plant pathologists, botanists, ecologists and those who are interested in palms and their relationship with ecological sustainability.

Gut microbiota dysbiosis in ankylosing spondylitis: a systematic review and meta-analysis.

Background: Ankylosing spondylitis (AS) is a connective tissue disease that primarily affects spinal joints, peripheral joints, and paravertebral soft tissues, leading to joint stiffness and spinal deformity. Growing evidence has implicated gut microbiota in the regulation of AS, though the underlying mechanisms remain poorly understood. Methods: We conducted a comprehensive search of PubMed, Embase, Web of Science, the Cochrane Library, MEDLINE, Wanfang Data, China Science and Technology Journal Database (VIP), and China National Knowledge Internet (CNKI) databases from the time the databases were created until 30 July 2023. To evaluate changes in α-diversity and the abundance of certain microbiota families in AS, standardized mean difference (SMD) and 95% confidence interval (CI) calculations were made. Meta-analyses were performed using STATA 12.0 and the quality of the literature was assessed by following systematic review guidelines. Results: This systematic review and meta-analysis included 47 studies, providing insights into the gut microbiota composition in patients with AS compared to healthy controls (HCs). Our findings indicate a significant reduction in gut microbial diversity in patients with AS, as evidenced by a decrease in both richness and evenness. Specifically, the Shannon index showed a moderate decrease (SMD = -0.27, 95% CI: -0.49, -0.04; P < 0.001), suggesting a less diverse microbial ecosystem in patients with AS. The Chao1 index further confirmed this trend, with a larger effect size (SMD = -0.44, 95% CI: -0.80, -0.07; P < 0.001), indicating a lower species richness. The Simpson index also reflected a significant reduction in evenness (SMD = -0.30, 95% CI: -0.53, -0.06; P < 0.001). Additionally, patients with AS who received anti-rheumatic combination treatment exhibited a more pronounced reduction in α-diversity compared to untreated patients, highlighting the potential impact of this treatment on gut microbiota balance. In terms of specific microbial families, we observed a significant decrease in the abundance of Bifidobacterium (SMD = -0.42, 95% CI: -2.37, 1.52; P < 0.001), which is known for its beneficial effects on gut health. Conversely, an increase in the abundance of Bacteroidetes was noted (SMD = 0.42, 95% CI: -0.93, 1.76; P < 0.001), suggesting a possible shift in the gut microbiota composition that may be associated with AS pathophysiology. Conclusion: Our analysis revealed changes in α-diversity and the relative abundance of specific bacteria in AS. This suggests that targeting the gut microbiota could provide new therapeutic opportunities for treating AS. Systematic review registration: https://www.crd.york.ac.uk./PROSPERO/, identifier CRD42023450028.

A human organoid drug screen identifies α2-adrenergic receptor signaling as a therapeutic target for cartilage regeneration.

Directed differentiation of stem cells toward chondrogenesis in vitro and in situ to regenerate cartilage suffers from off-target differentiation and hypertrophic tendency. Here, we generated a cartilaginous organoid system from human expanded pluripotent stem cells (hEPSCs) carrying a COL2A1mCherry and COL10A1eGFP double reporter, enabling real-time monitoring of chondrogenesis and hypertrophy. After screening 2,040 FDA-approved drugs, we found that α-adrenergic receptor (α-AR) antagonists, especially phentolamine, stimulated chondrogenesis but repressed hypertrophy, while α2-AR agonists reduced chondrogenesis and induced hypertrophy. Phentolamine prevented cartilage degeneration in hEPSC cartilaginous organoid and human cartilage explant models and stimulated microfracture-activated endogenous skeletal stem cells toward hyaline-like cartilage regeneration without fibrotic degeneration in situ. Mechanistically, α2-AR signaling induced hypertrophic degeneration via cyclic guanosine monophosphate (cGMP)-dependent secretory leukocyte protease inhibitor (SLPI) production. SLPI-deleted cartilaginous organoid was degeneration resistant, facilitating large cartilage defect healing. Ultimately, targeting α2-AR/SLPI was a promising and clinically feasible strategy to regenerate cartilage via promoting chondrogenesis and repressing hypertrophy.

The dysfunction of complement and coagulation in diseases: the implications for the therapeutic interventions.

The complement system, comprising over 30 proteins, is integral to the immune system, and the coagulation system is critical for vascular homeostasis. The activation of the complement and coagulation systems involves an organized proteolytic cascade, and the overactivation of these systems is a central pathogenic mechanism in several diseases. This review describes the role of complement and coagulation system activation in critical illness, particularly sepsis. The complexities of sepsis reveal significant knowledge gaps that can be compared to a profound abyss, highlighting the urgent need for further investigation and exploration. It is well recognized that the inflammatory network, coagulation, and complement systems are integral mechanisms through which multiple factors contribute to increased susceptibility to infection and may result in a disordered immune response during septic events in patients. Given the overlapping pathogenic mechanisms in sepsis, immunomodulatory therapies currently under development may be particularly beneficial for patients with sepsis who have concurrent infections. Herein, we present recent findings regarding the molecular relationships between the coagulation and complement pathways in the advancement of sepsis, and propose potential intervention targets related to the crosstalk between coagulation and complement, aiming to provide more valuable treatment of sepsis.

Dynamic changes of neutralizing antibody and memory T cell responses six months post Omicron XBB reinfection.

Introduction: With the continued prevalence of COVID-19, repeated infection caused by SARS-CoV-2 has become common. However, studies on immune persistence post Omicron XBB reinfection are limited. Methods: We prospectively studied the durability and cross-reactivity of neutralizing antibodies (NAbs) and T cell responses among 20 subjects who suffered Omicron BA.5 infection with or without Omicron XBB reinfection over 6-month through the pseudovirus neutralization test and the fluorospot assay. Results: NAbs against EG.5.1, BA.2.86, and JN.1 subvariants were decreased and undetectable at 6-month post Omicron BA.5 infection, while those elicited by Omicron XBB reinfection were significant increased and remained detectable against all detected variants within 6-month. Furthermore, in subjects with Omicron XBB reinfection, memory T cell responses could cross-recognized wild-type and Omicron spike peptides and reached peak at 3-month. Interestingly, comparable robust T cell responses were observed among non-seroconverted subjects post Omicron XBB exposure. Conclusion: Though the NAbs against various emerging Omicron subvariants elicited by Omicron XBB reinfection can persist for at least 6-month, the HCWs should strengthen personal protection and timely be immunized with updated vaccines upon current circulating variants or conserved T epitope.

Serum Extracellular Vesicles Reveal Metabolic Responses to Time-Restricted Feeding in High Fat Diet-Induced Obesity in Male Mice.

Objective: Extracellular vesicle (EV) secretion and cargo composition are dysregulated in metabolic diseases. This study aimed to identify changes in the EV size profile and protein cargoes in diet-induced obesity following time-restricted feeding (TRF) and to establish the role of EVs in obesity-related metabolic responses. Methods: Mice were fed a high-fat diet (HFD) for 18 weeks prior to being placed either ad libitum or a time-restricted feeding for an additional 10 weeks. Mice on a normal chow ad libitum served as the control. The TRF group had food available for 10 hours and fasted for 14 hours per day. Results: The serum EV size profile and amount displayed sex- and age-dependent changes in HFD-induced obesity, with age reducing EV amounts. HFD decreased small EV populations and increased larger EV populations, while TRF reversed these changes. Quantitative proteomic analysis showed that the abundance and composition of EV proteins changed in response to both acute stimulation with lipopolysaccharides (LPS) and HFD. Gene ontology analysis identified specific sets of EV proteins and their involved biological processes, reflecting the effect of LPS and HFD, as well as the reversal effect of TRF on metabolic and inflammatory pathways. EV proteins altered by HFD and those reversed by TRF had low protein overlap but significant functional overlap in biological processes. TRF activated the PPAR signaling pathway and the AKT-mTOR signaling pathway. The most significant impacts of HFD and TRF were observed on lipoprotein and carbohydrate metabolism, complement system, and neutrophil degranulation. The reversal effect of TRF on the complement system was pathway-specific, significantly activating the lectin complement pathway and restoring neutrophil degranulation. Conclusion: Our data indicate that EVs are involved in diet-induced metabolic and inflammatory responses. Different EV populations may carry distinct sets of proteins involved in specific biological processes, thereby regulating diverse metabolic pathways efficiently.

Uncovering seed vigor responsive miRNA in hybrid wheat and its parents by deep sequencing.

BACKGROUND: Two-line hybrid wheat technology system is one way to harness wheat heterosis both domestically and internationally. Seed vigor is a crucial parameter for assessing seed quality, as enhanced seed vigor can lead to yield increments of over 20% to a certain extent. MicroRNAs (miRNAs) were known to participate in the development and vigor of seed in plants, but its impact on seed vigor in two-line hybrid wheat remains poorly elucidated. RESULTS: The hybrid (BS1453/11GF5135) wheat exhibited superiority in seed vigor and anti-aging capacity, compared to its male parent (11GF5135, MP) and female parent (BS1453, FP). We identified four miRNAs associated with seed vigor, all of which are novel miRNAs. The majority of targets of miRNAs were related to ubiquitin ligases, kinases, sucrose synthases and hydrolases, involving in starch and sucrose metabolism, hydrolysis, catalysis, plant hormone signal transduction, and other pathways, which played crucial roles in seed development. Additionally, we also found miR531 was differentially expressed in both male parent and hybrid, and its target gene was a component of the E1 subunit of α-ketoate dehydrogenase complex, which interacted with dihydrolipoamide acetyltransferase (E2) and dihydrolipoyl dehydrogenase (E3). Finally, We established a presumptive interaction model to speculate the relationship of miR531 and seed vigor. CONCLUSIONS: This study analyzed the seed vigor of two-line hybrid wheat, and screened seed vigor-related miRNAs. Meanwhile speculated the genetic relationship of hybrid and parents, in terms of miRNAs. Consequently, the present study provides new insights into the miRNA-mediated gene and protein interaction network that regulates seed vigor. These findings hold significance for enhancing the yield and quality of two-line hybrid wheat, facilitating its future applications.

Incremental prognostic value of 18F-FDG myocardial ischemic memory imaging for major adverse cardiovascular events in patients with suspected unstable angina.

BACKGROUND: The additional prognostic value of 18F-FDG PET myocardial ischemic memory imaging for patients with suspected unstable angina (UA) is not well established. This study aimed to determine whether 18F-FDG PET imaging provides incremental prognostic information for predicting major adverse cardiac events (MACE) compared to clinical risk factors, GRACE score, and coronary artery calcium score (CACS) in suspected UA patients. METHODS: In this post-hoc analysis of a prospective study, 265 suspected UA patients (62.3% male, mean age 65.0±9.4 years) were enrolled. 18F-FDG positive was defined as focal or focal on diffuse uptake patterns. MACE included cardiovascular death, acute myocardial infarction, heart failure, rehospitalization for UA, and stroke. Multivariable Cox regression was used to identify predictors of MACE, and the incremental prognostic value of 18F-FDG PET imaging was assessed using C-index, net reclassification improvement (NRI), and integrated discrimination improvement (IDI). RESULTS: Over a median follow-up of 25 months, 51 patients (19.2%) experienced MACE. 18F-FDG positive (HR=3.220, 95% CI: 1.630-6.360, P<0.001) , as well as 18F-FDG standardized uptake ratio (SUR) (HR=1.330, 95%CI: 1.131-1.564, P=0.0006) and Extent (HR=1.045, 95%CI: 1.028-1.062, P<0.0001), were independent predictors of MACE. The addition of 18F-FDG PET imaging significantly improved risk stratification beyond clinical factors, the GRACE score, and CACS, with improved C-index (0.769 vs 0.688, P=0.045), NRI (0.324, P=0.020), and IDI (0.055, P=0.027). CONCLUSION: 18F-FDG PET myocardial ischemic memory imaging significantly improves prognostic assessment for suspected UA patients, providing valuable additional risk stratification beyond clinical risk factors, GRACE score, and CACS.

Epidemiological and immunological characteristics of middle-aged and elderly people in housing estates after Omicron BA.5 wave in Jinan, China.

A great number of COVID-19 patients was caused by Omicron BA.5 subvariant between December 2022 and January 2023 after the end of the zero-COVID-19 policy in China. In this study, we clarified the epidemiological and immunological characteristics of 457 enrolled middle-aged and elderly population in two housing estates after Omicron BA.5 wave. A total of 89.9 % (411/457) individuals have suffered Omicron BA.5 infection, among which 78.1 % (321/411) were symptomatic. The elderly patients were more likely to show fatigue and had longer symptomatic period than that of middle-aged patients post Omicron BA.5 infection. Omicron XBB and BA.2.86 subvariants extensively escaped the immunity elicited by Omicron BA.5 infection. The level of neutralizing antibody was mostly affected by vaccination doses rather than underlying disease status in these participants. It is very important to strengthen the epidemiological investigation and immune resistance assessment among elderly population for control of emerging SARS-CoV-2 variants.

Enhancing cancer immunotherapy: Nanotechnology-mediated immunotherapy overcoming immunosuppression.

Immunotherapy is an important cancer treatment method that offers hope for curing cancer patients. While immunotherapy has achieved initial success, a major obstacle to its widespread adoption is the inability to benefit the majority of patients. The success or failure of immunotherapy is closely linked to the tumor's immune microenvironment. Recently, there has been significant attention on strategies to regulate the tumor immune microenvironment in order to stimulate anti-tumor immune responses in cancer immunotherapy. The distinctive physical properties and design flexibility of nanomedicines have been extensively utilized to target immune cells (including tumor-associated macrophages (TAMs), T cells, myeloid-derived suppressor cells (MDSCs), and tumor-associated fibroblasts (TAFs)), offering promising advancements in cancer immunotherapy. In this article, we have reviewed treatment strategies aimed at targeting various immune cells to regulate the tumor immune microenvironment. The focus is on cancer immunotherapy models that are based on nanomedicines, with the goal of inducing or enhancing anti-tumor immune responses to improve immunotherapy. It is worth noting that combining cancer immunotherapy with other treatments, such as chemotherapy, radiotherapy, and photodynamic therapy, can maximize the therapeutic effects. Finally, we have identified the challenges that nanotechnology-mediated immunotherapy needs to overcome in order to design more effective nanosystems.

Comparison between arthroplasty and non-operative treatment for proximal humeral fractures: a systematic review and meta-analysis.

Background: The clinical efficacy of reverse shoulder arthroplasty (RSA), hemiarthroplasty (HA), and non-surgical management in the treatment of proximal humeral fractures (PHFs) is inconclusive. This systematic review and meta-analysis compared the clinical outcomes of arthroplasty and non-surgical management of PHFs. Methods: The databases of PubMed, Embase, Web of Science, and Cochrane Library were searched on 5 May 2023 for studies comparing arthroplasty and non-surgical treatment of PHFs. Both randomized controlled trials (RCTs) and non-randomized controlled trials (nRCTs), were included. Standard methodological quality assessments were conducted for both types of studies. The primary outcome was the Constant-Murley Score (CMS) after surgical or non-surgical treatment. Secondary study outcomes included the visual analog scale (VAS), range of motion, and complications. All functional scores and complications were subjected to subgroup and sensitivity analyses. Results: A total of four RCTs and six nRCTs were included in this study, which provided 508 patients in total for meta-analysis: 238 treated with arthroplasty and 270 treated non-surgically, of which 83 were treated with HA and 155 with RSA. All relevant information was collected, including functional scores, VAS, range of motion, and complications. The study found no significant difference in functional outcomes (mean difference, 2.82; 95% confidence interval, -0.49 to 6.14; P = 0.10; I 2 = 77%) and complications (mean difference, 1.08; 95% confidence interval, 0.51-2.25; P = 0.85; I 2 = 47%) between arthroplasty and non-surgical treatment. Both RCTs and nRCTs showed the same results. However, VAS scores were significantly lower in surgical treatment compared to non-surgical treatment. Subgroup and sensitivity analyses showed that RSA could achieve better functional scores than non-surgical treatment (mean difference, 6.00; 95% confidence interval, 1.97-10.03; P = 0.004; I 2 = 0%), while the results for HA were not significant (P > 0.05). Conclusion: There were no significant differences in complications between arthroplasty and non-surgical treatment for PHFs. RSA could achieve better functional results than non-surgical treatment, while HA could only achieve better forward flexion.