Artificial intelligence and machine learning applications in urinary tract infections identification and prediction: a systematic review and meta-analysis.

BACKGROUND: Urinary tract infections (UTIs) have been one of the most common bacterial infections in clinical practice worldwide. Artificial intelligence (AI) and machine learning (ML) based algorithms have been increasingly applied in UTI case identification and prediction. However, the overall performance of AI/ML algorithms in identifying and predicting UTI has not been evaluated. The purpose of this paper is to quantitatively evaluate the application value of AI/ML in identifying and predicting UTI cases. METHODS: MEDLINE, EMBASE, Web of Science, and PubMed databases were systematically searched for articles published up to December 31, 2023. Quality Assessment of Diagnostic Accuracy Studies tool (QUADAS-2) and Prediction Model Risk of Bias Assessment Tool (PROBAST) were used to assess the risk of bias. Study characteristics and detailed algorithm information were extracted. Pooled sensitivity, specificity, and area under the receiver operating characteristic curve (AUC) were synthesized using a bivariate mix-effects model. Meta-regression and subgroup analysis were conducted to test the source of heterogeneity. RESULTS: In total, 11 studies with 14 AI/ML models were included in the final meta-analysis. The overall pooled AUC was 0.89 (95%CI 0.86-0.92). Additionally, the pooled Sen, Spe, PLR, NLR, and DOR were 0.78 (95%CI 0.71-0.84), 0.89 (95%CI 0.83-0.93), 6.99 (95%CI 4.38-11.14), 0.25 (95%CI 0.18-0.34) and 28.07 (95%CI 14.27-55.20), respectively. The results of meta-regression suggested that reference standard definitions might be the source of heterogeneity. CONCLUSION: AI/ML algorithms appear to be promising to help clinicians detect and identify patients at high risk of UTIs. However, further studies are demanded to evaluate the application value of AI/ML more thoroughly.

Biodegradable magnesium and zinc composite microspheres with synergistic osteogenic effect for enhanced bone regeneration.

Biodegradable polymer microspheres in bone tissue engineering have become appealing as their non-invasive advantages in irregular damage bone repair. However, current microspheres used in BTE still lack sufficient osteogenic capacity to induce effective bone regeneration. In this study, we developed osteogenic composite microspheres concurrently loaded with magnesium oxide (MgO) and zinc oxide (ZnO), both of which are osteogenic active substances, using a facile and scalable emulsification method. The osteogenic composite microspheres exhibited a sequential yet complementary release profile characterized by a rapid release of Mg2+ and a gradual release of Zn2+ in a physiological environment, thereby maintaining the concentration of bioactive ions at a sustained high level. As a result, the combination of Mg2+ and Zn2+ in the composite microspheres led to a synergistic enhancement in biomimetic mineralization and the upregulation in the expression of osteogenic-related genes and proteins at the cellular level. Through a critical-sized calvarial rate defect model, the osteogenic composite microspheres were demonstrated to have strong osteogenic ability to promote new bone formation via ultrasonic imaging, histological and immunohistochemical evaluations. In sum, these osteogenic composite microspheres as microcarriers of Mg2+ and Zn2+ have great potential in the delivery of therapeutic ions for treating bone defects.

Clinical features and prognostic model for viral encephalitis after allogeneic haematopoietic stem cell transplantation.

The objective of this study was to identify independent prognostic factors of viral encephalitis (VE) after allogeneic haematopoietic stem cell transplantation (allo-HSCT) and establish a prognostic model to identify post-transplant VE patients with a greater likelihood of mortality. Among 5380 patients in our centre from 2014 to 2022, 211 patients who developed VE after allo-HSCT were reviewed in this retrospective study. Prognostic factors were selected, and a prognostic model was constructed using Cox regression analysis. The model was subsequently validated and estimated using the area under the receiver operating characteristic curve (AUC), a calibration plot and decision curve analysis (DCA). Glasgow Coma Scale score <9, lesions >3 lobes on magnetic resonance imaging and severe thrombocytopenia were identified as independent prognostic risk factors for VE patients who underwent allo-HSCT. The prognostic model GTM (GTM is an abbreviation for a model composed of three risk factors: GCS score <9, severe thrombocytopenia [platelet count <20 000 per microliter], and lesions >3 lobes on MRI) was established according to the regression coefficients. The validated internal AUC was 0.862 (95% confidence interval [CI], 0.773-0.950), and the external AUC was 0.815 (95% CI, 0.708-0.922), indicating strong discriminatory ability. Furthermore, we constructed calibration plots that demonstrated good consistency between the predicted outcomes and the observed outcomes. DCA exhibited high accuracy in this system, leading to potential benefits for patients.

Increased age and the volume of intraoperative fluid administered predict urinary retention after elective inguinal herniorrhaphy.

BACKGROUND: Inguinal hernia repair (IHR) is a common surgical procedure worldwide. Although IHR can be performed by the minimally invasive method, which accelerates recovery, postoperative urinary retention (POUR) remains a common complication that significantly impacts patients. Thus, it is essential to identify the risk factors associated with POUR to diminish its negative impact. METHODS: We conducted a single-center retrospective review of elective IHR from 2018 to 2021. POUR was defined as the postoperative use of straight catheter or placement of an indwelling catheter to relieve the symptoms. Adjusted multivariate regression analysis was performed to address the associations of clinicodemographic, surgical, and intraoperative factors with POUR. RESULTS: A total of 946 subjects were included in the analysis after excluding cases of emergent surgery, recurrent hernia, or concomitant operations. The median age was 68.4 years, and 92.0% of the patients were male. Twenty-three (2.4%) patients developed POUR. In univariate analysis, POUR in comparison with non-POUR was significantly associated with increased age (72.2 versus 68.3 years, P = 0.012), a greater volume of intraoperative fluid administered (500 versus 400 ml, P = 0.040), and the diagnosis with benign prostate hypertrophy (34.8% versus 16.9%, P = 0.025). In the multivariate model, both increased age (odds ratio [OR] 1.04, 95% CI 1.01-1.08; P = 0.049) and a greater volume of intraoperative fluid administered (OR 1.12 per 100-mL increase, 95% CI 1.01-1.27; P = 0.047) were significantly associated with the occurrence of POUR. CONCLUSIONS: We found that increased age and a greater volume of intraoperative fluid administered were significantly associated with the occurrence of POUR. Limiting the administration of intraoperative fluid may prevent POUR. From the perspective of practical implications, specific guidelines or clinical pathways should be implemented for fluid management and patient assessment.

Novel glucomannan-like polysaccharide from Lycium barbarum L. ameliorates renal fibrosis via blocking macrophage-to-myofibroblasts transition.

The macrophage to myofibroblasts transition (MMT) has been reported as a newly key target in renal fibrosis. Lycium barbarum L. is a traditional Chinese medicine for improving renal function, in which its polysaccharides (LBPs) are the mainly active components. However, whether the role of LBPs in treating renal fibrosis is related to MMT process remain unclear. The purpose of this study was to explore the relationship between the regulating effect on MMT process and the anti-fibrotic effect of LBPs. Initially, small molecular weight LBPs fractions (LBP-S) were firstly isolated via Sephadex G-100 column. Then, the potent inhibitory effect of LBP-S on MMT process was revealed on bone marrow-derived macrophages (BMDM) model induced by TGF-ß. Subsequently, the chemical structure of LBP-S was elucidated through monosaccharide, methylation and NMR spectrum analysis. In vivo biodistribution characteristics studies demonstrated that LBP-S exhibited effectively accumulation in kidney via intraperitoneal administration. Finally, LBP-S showed a satisfactory anti-renal fibrotic effect on unilateral ureteral obstruction operation (UUO) mice, which was significantly reduced following macrophage depletion. Overall, our findings indicated that LPB-S could alleviate renal fibrosis through regulating MMT process and providing new candidate agents for chronic kidney disease (CKD) related fibrosis treatment.

Hypoxia and ferroptosis.

Ferroptosis is a novel, iron-dependent cell death characterized by the excessive accumulation of ferroptosis lipid peroxides ultimately leading to oxidative damage to the cell membrane. Iron, lipid, amino acid metabolism, and other signaling pathways all control ferroptosis. Numerous bodily tissues experience hypoxia under normal and pathological circumstances. Tissue cells can adjust to these changes by activating the hypoxia-inducible factor (HIF) signaling pathway and other mechanisms in response to the hypoxic environment. In recent years, there has been increasing evidence that hypoxia and ferroptosis are closely linked, and that hypoxia can regulate ferroptosis in specific cells and conditions through different pathways. In this paper, we review the possible positive and negative regulatory mechanisms of ferroptosis by hypoxia-inducible factors, as well as ferroptosis-associated ischemic diseases, with the intention of delivering novel therapeutic avenues for the defense and management of hypoxic illnesses linked to ferroptosis.

Redox-Responsive AIEgen Diselenide-Covalent Organic Framework Composites Targeting Hepatic Macrophages for Treatment of Drug-induced Liver Injury.

The escalating misuse of antipyretic and analgesic drugs, alongside the rising incidents of acute drug-induced liver injury, underscores the need for a precisely targeted drug delivery system. Herein, two isoreticular covalent organic frameworks (Se-COF and Se-BCOF) are developed by Schiff-base condensation of emissive tetraphenylethylene and diselenide-bridged monomers. Leveraging the specific affinity of macrophages for mannose, the first precise targeting of these COFs to liver macrophages is achieved. The correlation is also explored between the therapeutic effects of COFs and the NLRP3/ASC/Caspase-1 signaling pathway. Utilizing this innovative delivery vehicle, the synergistic delivery of matrine and berberine are accomplished, compounds extracted from traditional Chinese medicine. This approach not only demonstrated the synergistic effects of the drugs but also mitigated their toxicity. Notably, berberine, through phosphorylation of JNK and up-regulation of nuclear Nrf-2 and its downstream gene Mn-SOD expression, simultaneously countered excessive ROS and suppressed the activation of the NLRP3/ASC/Caspase-1 signaling pathway in injured liver tissues. This multifaceted approach proved highly effective in safeguarding against acute drug-induced liver injury, ultimately restoring liver health to normalcy. These findings present a novel and promising strategy for the treatment of acute drug-induced liver injury.

Retrograde tibial intramedullary nail versus minimally invasive locking plate for extra-articular distal tibial fractures: a comparative and retrospective study.

BACKGROUND: Distal tibial fractures represent common lower limb injuries, frequently accompanied by significant soft tissue damage. The optimal surgical approach for managing these fractures remains a topic of considerable debate. The aim of this study was to perform a comparative analysis of the outcomes associated with retrograde intramedullary tibial nails (RTN) and minimally invasive plate osteosynthesis (MIPO) in the context of treating extra-articular distal tibial fractures. METHODS: A retrospective review was conducted on a cohort of 48 patients who sustained extra-articular distal tibial fractures between December 2019 and December 2021. Patients underwent either RTN or MIPO procedures. Various parameters, including operative duration, intraoperative fluoroscopy exposure, time to union, duration until full weight-bearing, American Orthopedic Foot and Ankle Society (AOFAS) scores, and complications, were recorded and compared between the two treatment groups. RESULTS: No statistically significant differences were observed in operative duration, time to union, angulation of the distal tibial coronal plane, or AOFAS scores between the RTN and MIPO groups. However, the RTN group had a higher average number of intraoperative fluoroscopy images (8.2 ± 2.3) compared to the MIPO group (4.1 ± 2.0). The RTN group demonstrated shorter average hospital stays (7.1 ± 1.4 days) and a quicker return to full weight-bearing (9.9 ± 1.3 weeks), which were significantly superior to the MIPO group (9.0 ± 2.0 days and 11.5 ± 1.5 weeks, respectively). In terms of complications, the RTN group had one case of superficial infection, whereas the MIPO group exhibited two cases of delayed union and nonunion, two occurrences of deep infection, and an additional three cases of superficial infection. CONCLUSIONS: Both RTN and MIPO are effective treatment options for extra-articular distal tibial fractures. However, RTN may offer superior outcomes in terms of decreased inpatient needs, faster return to full weight-bearing capacity, and a lower rate of complications.

Clinical effect of botulinum toxin type A combined with autologous fat grafting in patients with nasolabial fold depression.

BACKGROUND: Nasolabial fold (NLF) depression can affect the facial appearance of patients to some extent and increase their psychological burdens. In recent years, autologous fat grafting (AFG) combined with botulinum toxin A (BTX-A) injection (AFG + BTX-A injection) has been gradually applied in the treatment of patients with NLF depression. Although studies have been conducted on the efficacy and safety of AFG + BTX-A injection in treating NLF depression, the experimental design, observational indicators, and sample enrollment criteria vary remarkably, making it difficult to draw convincing and consistent conclusions. Thus, further relevant research is warranted. AIM: To assess the esthetic improvement, efficacy, and safety of AFG + BTX-A injections in patients with NLF depression. METHODS: This study included 60 patients with NLF depression who were treated in our hospital from February 2019 to April 2021. These patients were categorized into control (n = 30) and observation (n = 30) groups. The observation group received AFG + BTX-A injection, whereas the control group underwent AFG only. All patients were evaluated using the wrinkle severity rating scale (WSRS) and global aesthetic improvement scale. The compactness of facial contours, skin evaluation indexes, adverse reactions, and satisfaction of the two groups were evaluated 3 months postoperatively. RESULTS: The WSRS scores of the observation group at 1, 3, and 6 months postoperatively were lower than those of the control group (P < 0.05). Three months postoperatively, facial fine lines and pores showed obvious improvement and the skin index score was higher in the observation group than in the control group (P < 0.05). The compactness of facial contours was better in the observation group than in the control group (P < 0.05). In addition, no remarkable differences were noted in the incidence of postoperative adverse reactions such as facial stiffness, facial asymmetry, facial bruising, and facial concavity inequality (P > 0.05). CONCLUSION: AFG + BTX-A injection is a highly safe, cost-effective, effective, and long-lasting treatment for NLF depression with high esthetic value, which should be promoted in the future.

Anemia after pancreaticoduodenectomy in patients followed-up for 5 years.

BACKGROUND: Anemia is a common long-term metabolic sequela caused by anatomical changes after major gastrointestinal surgery, such as bariatric surgery and gastrectomy. Pancreaticoduodenectomy (PD) involves resection of the duodenum and enteral bypass, which may contribute to malabsorption and nutrient deficiency. Hence, PD may cause anemia. METHODS: This study included 322 patients who presented with PD during the 5-year follow-up from 2006 to 2017. The Kaplan-Meier method and the Cox regression model were used to investigate the association between risk factors and anemia. RESULTS: Approximately 44.4% of patients developed post-PD anemia during the 5-year post-PD follow-up. Further, 30 (9.3%) patients were treated with oral iron supplementation for anemia with associated symptoms. In the Cox multivariate model, a higher Charlson Comorbidity Index (CCI) score and pancreatic ductal adenocarcinoma were significantly associated with the development of post-PD anemia. CONCLUSION: Post-PD anemia is a common sequela among long-term survivors. A higher CCI and pancreatic ductal adenocarcinoma diagnosis were considered as independent risk factors for post-PD anemia. Therefore, regular monitoring of hematological profiles and appropriate management of post-PD anemia are required during follow-up.

The impact of emotion regulation strategies on disordered eating behavior in children and adolescents with type 1 diabetes: a cross-sectional study.

Objective: Difficulties in emotion regulation (DERs) can contribute to disordered eating behavior in children and adolescents with type 1 diabetes (T1D), although it is unknown how DERs may affect eating behavior in these children and adolescents. This study examined the relationship between disordered eating behaviors and emotion regulation in children and adolescents with T1D. Methods: For this cross-sectional study, 128 patients (aged 8-16 years) were recruited to complete the Diabetes Eating Problem Survey-Revised (DEPS-R) and Difficulties in Emotion Regulation Scale (DERs). Results: The mean age of the 128 patients (99 females) who completed the DEPS-R was 11.63 ± 2.27 years. The participants' mean DEPS-R score was 17.78 ± 8.56 points. Of the total sample, 61 participants' scores surpassed the established threshold, resulting in a DEPS-R positivity rate of 47.66%. The participants' mean total DERS score was 72.3 ± 21.15 points, and it was found that children and adolescents with T1D who had a positive DEPS-R screening result had significant differences in emotional regulation and that eating behavior disorders were positively correlated with emotional regulation and all dimensions scores. Conclusions: The prevalence of disordered eating behavior is high among children and adolescents with T1D. DERs are related to disordered eating behavior in children and adolescents with T1D. The novel finding that DERs may be a predictor of eating problems lends preliminary support for the inclusion of DERs in future risk models and as a potential target for intervention.

METTL3 Inhibition Suppresses Cell Growth and Survival in Colorectal Cancer via ASNS Downregulation.

Background: Colorectal cancer (CRC) presents a significant global health burden, with high rates of incidence and mortality, and an urgent need to improve prognosis. STM2457, a novel small molecule inhibitor specific for N6-methyladenosine (m6A) catalytic enzyme Methyltransferase-like 3 (METTL3) has implicated significant treatment potentials in a few of types of cancer. However, its impact and underlying mechanism are still unclear in CRC cells. Methods: We used CCK-8 and colony formation assay to observe cell growth, flow cytometry and TUNEL approaches to detect cell apoptosis under the treatment of STM2457 on CRC cells in vitro or in vivo. RNA-sequencing, qRT-PCR and western blotting were performed to explore downstream effectors of STM2457. Messenger RNA stability was evaluated by qRT-PCR after treatment with actinomycin D. The methylated RNA immunoprecipitation (MeRIP) qPCR, dual-luciferase reporter analyses and m6A dot blotting were carried out to measure the m6A modification. Associated gene expression pattern and clinical relevance in CRC clinical tissue samples were analyzed using online database. Results: STM2457 exhibited a strong influence on cell growth suppression and apoptosis of CRC cells in vitro and subcutaneous xenograft growth in vivo. Asparagine synthetase (ASNS) was markedly downregulated upon STM2457 treatment or METTL3 knockdown and exogenous overexpression of ASNS could rescue the biological defects induced by STM2457. Mechanistically, the downregulation of ASNS by STM2457 may be due to the decrease of m6A modification level in ASNS mRNA mediated by METTL3. Conclusions: Our findings suggest that STM2457 may serve as a potential therapeutic agent and ASNS may be a new promising therapeutic target for CRC.

[Multi-time Scale Variation of Atmospheric Ammonia Concentration and Dry Deposition in a Paddy Rice Region in Subtropical China].

Meteorological factors and anthropogenic activities significantly affect atmospheric ammonia （NH3） concentration and its dry deposition. Former studies have examined the spatial and temporal variability in atmospheric NH3 concentrations at monthly scales. However, the characteristics of atmospheric concentrations at finer time scales such as hourly and daily scales and the influencing factors remain unclear. In this study, atmospheric NH3 concentration and related meteorological factors were continuously monitored online for one year in a double cropping rice region in subtropical China, and atmospheric NH3 concentration and its meteorological influencing factors as well as dry deposition were analyzed at different time scales （hourly, daily, and monthly）. The main results were as follows： The annual average daily concentration of NH3 in the rice area varied from 0.01 to 58.0 µg·m-3 （in N, same below）, and the annual average concentration was 5.3 µg·m-3. On the hourly scale, the 24-hour dynamics of atmospheric NH3 concentration showed a unimodal pattern, and the time of the NH3 peak appearance in different seasons was different； the time of the peak that appeared in winter lagged behind that in the other seasons. From the perspective of daily scale, NH3 concentration was mainly affected by fertilization in the paddy fields, peaking at 1-3 days after fertilization and then gradually decreasing. On the monthly scale, NH3 concentration peaked at 12.8 µg·m-3 in July and was the lowest in October at 1.6 µg·m-3. On the hourly scale, NH3 concentration varied seasonally due to the influences of meteorological factors, mainly as follows： NH3 concentration showed significant positive correlations with air temperature and solar radiation in all four seasons and with wind speed in spring and summer, whereas it showed significant negative correlations with relative humidity except in winter. On the daily scale, NH3 concentration showed a significant positive correlation with air temperature, rainfall, and solar radiation, whereas it showed a significant negative correlation with relative humidity. On the monthly scale, no significant correlation existed between each meteorological factor and NH3 concentration. The annual dry deposition flux （in N） calculated from the hourly average NH3 concentration was 8.5 kg·ï¼ˆhm2·a）-1, which was 11.6% higher than the annual flux calculated from the daily average and 12.4% higher than the annual flux calculated from the monthly average. In summary, there were significant daily and seasonal variations in atmospheric NH3 concentration in the paddy rice region in subtropical China, and conducting hourly-scale observations of NH3 concentration can help to reveal the multi-time scale variations in NH3 concentration and to quantify NH3 dry deposition more accurately.

Clinical and genetic characteristics of Chinese patients with congenital fibrosis of the extraocular muscles.

OBJECTIVE: This study aimed to describe the clinical and genetic characteristics of Chinese patients with congenital fibrosis of the extraocular muscles (CFEOM), and to evaluate the phenotype-genotype correlations in these patients. METHODS: This was a retrospective study. Patients with CFEOM underwent detailed ophthalmic examinations and magnetic resonance imaging (MRI). Panel-based next-generation sequencing was performed to identify pathogenic variants of disease-causing genes. RESULTS: Sixty-two patients with CFEOM were recruited into this study. Thirty-nine patients were diagnosed with CFEOM1 and 23 with CFEOM3. Forty-nine of the 62 patients with CFEOM carried either KIF21A (41/49) or TUBB3 variants (8/49). Six known missense variants in the KIF21A and TUBB3 genes, and a novel variant (c.3906T > A, p.D1302E) in the KIF21A gene were detected. Most patients with CFEOM1 carrying the KIF21A mutation displayed isolated CFEOM, whereas patients with CFEOM3 carrying the TUBB3 mutation had a wide range of clinical manifestations, either CFEOM alone or syndromes. Nystagmus was also present in 12 patients with CFEOM. Furthermore, the MRI findings varied, ranging from attenuation of the extraocular muscles to dysgenesis of the cranial nerves and brain structure. CONCLUSIONS: The novel variants identified in this study will further expand the spectrum of pathogenic variants in CFEOM-related genes. However, no phenotype-genotype correlations were established because of the diversity of the clinical characteristics of these patients.

A luminescent Cu2I2P2S2-type binuclear complex and its fluorescence sensing for pyridine.

Luminescent CuI complexes are an important class of coordination compounds due to their relative abundance, low cost and ability to display excellent luminescence. The title Cu2I2P2S2-type binuclear complex, di-µ-iodido-bis[(thiourea-κS)(triphenylphosphine-κP)copper(I)], [Cu2I2(CH4N2S)2(C18H15P)2], conventionally abbreviated as Cu2I2TPP2TU2, where TPP and TU represent triphenylphosphine and thiourea, respectively, is described. In this complex, each CuI atom adopts a CuI2PS four-coordination mode and pairs of atoms are connected to each other by two µ2-I ligands to form a centrosymmetric binuclear cluster. It was also found that the paper-based film of this complex exhibited obvious luminescence light-up sensing for pyridine and 4-methylpyridine.

Separable cell cycle arrest and immune response elicited through pharmacological CDK4/6 and MEK inhibition in RASmut disease models.

The combination of CDK4/6 and MEK inhibition as a therapeutic strategy has shown promise in various cancer models, particularly in those harboring RAS mutations. An initial high-throughput drug screen identified a high synergy between the CDK4/6 inhibitor palbociclib and the MEK inhibitor trametinib when used in combination in soft tissue sarcomas. In RAS mutant models, combination treatment with palbociclib and trametinib induced significant G1 cell cycle arrest, resulting in a marked reduction in cell proliferation and growth. CRISPR-mediated RB1 depletion resulted in a decreased response to CDK4/6 and MEK inhibition, which was validated in both cell culture and xenograft models. Beyond its cell cycle inhibitory effects, pathway enrichment analysis revealed the robust activation of interferon pathways upon CDK4/6 and MEK inhibition. This induction of gene expression was associated with the upregulation of retroviral elements. The TBK1(TANK-binding kinase 1) inhibitor GSK8612 selectively blocked the induction of interferon-related genes induced by palbociclib and trametinib treatment, and highlighted the separable epigenetic responses elicited by combined CDK4/6 and MEK inhibition. Together, these findings provide key mechanistic insights into the therapeutic potential of CDK4/6 and MEK inhibition in soft tissue sarcoma.

Clinical characteristics of membranous nephropathy after allogeneic hematopoietic stem cell transplantation: A real-world multicenter study.

Membranous nephropathy (MN) is a rare complication that can occur after allogeneic hematopoietic stem cell transplantation (allo-HSCT). MN patients may develop nephrotic syndrome or even kidney failure, which greatly affects their quality of life and prognosis. However, current knowledge regarding MN after allo-HSCT is limited. Thus, a multicenter nested case‒control study was conducted. Patients who had been diagnosed with MN after allo-HSCT were retrospectively identified at 8 HSCT centers. A total of 51 patients with MN after allo-HSCT were included. The median age of MN patients after allo-HSCT was 38 years, and the median duration from HSCT to MN was 18 months. The use of HLA-matched donors (P = 0.0102) and peripheral blood as the graft source (P = 0.0060) were identified as independent predisposing risk factors for the onset of MN after allo-HSCT. Compared to those in the control group, the incidence of extensive chronic graft-versus-host disease was greater in the MN patients (P = 0.0002). A total of 31 patients developed nephrotic syndrome. Patients receiving combination treatments of corticosteroids and immunosuppressants appeared to have better outcomes. In conclusion, MN is a rare but occasionally severe complication following HSCT and may require active treatment.

Modulation of cardiac resident macrophages immunometabolism upon high-fat-diet feeding in mice.

Background: A high-fat diet (HFD) contributes to various metabolic disorders and obesity, which are major contributors to cardiovascular disease. As an essential regulator for heart homeostasis, cardiac resident macrophages may go awry and contribute to cardiac pathophysiology upon HFD. Thus, to better understand how HFD induced cardiac dysfunction, this study intends to explore the transcriptional and functional changes in cardiac resident macrophages of HFD mice. Methods: C57BL/6J female mice that were 6 weeks old were fed with HFD or normal chow diet (NCD) for 16 weeks. After an evaluation of cardiac functions by echocardiography, mouse hearts were harvested and cardiac resident CCR2- macrophages were sorted, followed by Smart sequencing. Bioinformatics analysis including GO, KEGG, and GSEA analyses were employed to elucidate transcriptional and functional changes. Results: Hyperlipidemia and obesity were observed easily upon HFD. The mouse hearts also displayed more severe fibrosis and diastolic dysfunction in HFD mice. Smart sequencing and functional analysis revealed metabolic dysfunctions, especially lipid-related genes and pathways. Besides this, antigen-presentation-related gene such as Ctsf and inflammation, particularly for NF-κB signaling and complement cascades, underwent drastic changes in cardiac resident macrophages. GO cellular compartment analysis was also performed and showed specific organelle enrichment trends of the involved genes. Conclusion: Dysregulated metabolism intertwines with inflammation in cardiac resident macrophages upon HFD feeding in mice, and further research on crosstalk among organelles could shed more light on potential mechanisms.

Role of cell division cycle-associated proteins in regulating cell cycle and promoting tumor progression.

The cell division cycle-associated protein (CDCA) family is important in regulating cell division. High CDCA expression is significantly linked to tumor development. This review summarizes clinical and basic studies on CDCAs conducted in recent decades. Furthermore, it systematically introduces the molecular expression and function, key mechanisms, cell cycle regulation, and roles of CDCAs in tumor development, cell proliferation, drug resistance, invasion, and metastasis. Additionally, it presents the latest research on tumor diagnosis, prognosis, and treatment targeting CDCAs. These findings are pivotal for further in-depth studies on the role of CDCAs in promoting tumor development and provide theoretical support for their application as new anti-tumor targets.

Ghrelin Improves Glucolipotoxicity-Induced Pancreatic ß-Cellular Dysfunction and Apoptosis by Inhibiting Endoplasmic Reticulum Stress-Induced IRE1/JNK Pathway.

BACKGROUND: Glucose and fatty acid overload-induced glucolipid toxicity of pancreatic ß-cells is associated with the development of diabetes. Endoplasmic reticulum stress (ERS) plays an essential role in this process. Ghrelin, a peptide secreted by the pancreas, negatively correlates with oxidative stress. The study aimed to investigate ghrelin's role in glycolipid-induced ß-cell dysfunction and its possible mechanism. METHODS: Mouse insulinoma ß-cell, NIT-1 cells, were stimulated with high fat and high glucose to induce glucolipid toxicity. High fat and high glucose-induced NIT-1 cells were treated with acylated ghrelin (AG) or [d-Lys3]-growth hormone releasing peptide (GHRP)-6. Flow cytometry and Cell Counting Kit-8 (CCK-8) assay were performed to assess apoptosis and cell viability. The protein expression related to apoptosis, inositol-requiring kinase 1 (IRE1)/c-Jun N-terminal kinase (JNK) signaling, and ERS were investigated using western blot. Enzyme-linked immunosorbent assay (ELISA) was adopted to examine insulin's synthesis and secretion levels. RESULTS: Ghrelin treatment improved cell viability while inhibiting cell glucolipotoxicity-induced NIT-1 cell apoptosis. Ghrelin can promote the synthesis and secretion of insulin in NIT-1 cells. Mechanistically, ghrelin attenuates ERS and inhibits the IRE1/JNK signaling pathway in NIT-1 cells induced by glucolipotoxicity. CONCLUSION: Ghrelin improves ß-cellular dysfunction induced by glucolipotoxicity by inhibiting the IRE1/JNK pathway induced by ERS. It could be an effective treatment for ß-cellular dysfunction.