Treatment Challenges Research Articles

Association of Neurofibromatosis Type 1 and Multiple Sclerosis: A Case Report

Neurofibromatosis type 1 (NF1) is an autosomal dominant neurocutaneous disorder, while multiple sclerosis (MS) is a prevalent chronic inflammatory demyelinating disease of the central nervous system. The coexistence of these two conditions is rare. Thus, patients with NF1 may exhibit signal abnormalities on brain imaging, referred to as focal areas of signal intensity (FASI), which can mimic lesions seen in MS and complicate the differential diagnosis. We present the case of a female patient suffering from progressive paraparesis, accompanied by urinary disorders and coordination disorders of the upper limbs. Neurological examination revealed a pyramidal syndrome and a cerebellar syndrome, with an Expanded Disability Status Scale (EDSS) score of 7.5. Additionally, the skin examination showed multiple café-au-lait spots larger than 15 mm and numerous diffuse neurofibromas. Brain magnetic resonance imaging showed white matter lesions typical of MS, and isoelectrofocalization of cerebrospinal fluid proteins revealed positive oligoclonal bands. The diagnosis was primary progressive multiple sclerosis associated with neurofibromatosis type 1. The aim of this case report is to document the association of these two conditions and discuss the challenges in differential diagnosis and treatment, as early diagnosis of MS is crucial to prevent further disability in patients with NF1.

Sexually transmitted infections among at-risk women in Ecuador: implications for global prevalence and testing practices for STIs detected only at the anorectum in female sex workers

ObjectivesAnorectal sexually transmitted infections (STIs) such as Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG), present treatment challenges, potentially increase antibiotic resistance selection and if undetected may facilitate onward transmission. However,...

Full-scale study on high-rate low-temperature anaerobic digestion of agro-food wastewater: process performances and microbial community.

The fast-growing global population has led to a substantial increase in food production, which generates large volumes of wastewater during the process. Despite most industrial wastewater being discharged at lower ambient temperatures (<20 °C), majority of the high-rate anaerobic reactors are operated at mesophilic temperatures (>30 °C). High-rate low-temperature anaerobic digestion (LtAD) has proven successful in treating industrial wastewater both at laboratory and pilot scales, boasting efficient organic removal and biogas production. In this study, we demonstrated the feasibility of two full-scale high-rate LtAD bioreactors treating meat processing and dairy wastewater, and the microbial communities in both reactors were examined. Both reactors exhibited rapid start-up, achieving considerable chemical oxygen demand (COD) removal efficiencies (total COD removal >80%) and generating high-quality biogas (CH4% in biogas >75%). Long-term operations (6-12 months) underscored the robustness of LtAD bioreactors even during winter periods (average temperature <12 °C), as evidenced by sustained high COD removal rates (total COD removal >80%). The stable performance was underpinned by a resilient microbial community comprising active acetoclastic methanogens, hydrolytic, and fermentative bacteria. These findings underscore the feasibility of high-rate low-temperature anaerobic wastewater treatment, offering promising solutions to the zero-emission wastewater treatment challenge.

The Impact of Combined Application of Donepezil and Nimodipine on Patients with Comorbid Cerebral Small Vessel Disease and Cognitive Dysfunction: Efficacy and Influence on Nutritional Status.

Cerebral small vessel disease (CSVD) often coexists with cognitive dysfunction in patients, leading to significant challenges in treatment and management. This study aimed to examine the efficacy of combined application of donepezil and nimodipine on patients with comorbid CSVD and cognitive dysfunction and the effects on patients' albumin and prealbumin levels. The records of 112 patients with comorbid CSVD and cognitive dysfunction treated at the People's Hospital of Suzhou New District from January 2019 to December 2022 were analysed retrospectively. A total of 50 patients receiving donepezil were allocated to the control group, and 62 patients receiving both nimodipine and donepezil to the study group. Outcomes compared between the two groups included serum homocysteine (Hcy), high sensitivity C-reactive protein (hs-CRP), albumin, and prealbumin before and after therapy, efficacy, and adverse reactions. Additionally, logistic regression was performed to analyze the risk factors impacting patient prognosis. Prior to therapy, the two groups did not differ significantly in Hcy and hs-CRP levels (p > 0.05), whereas after therapy, the levels in both groups dropped significantly (p < 0.01), with more obvious lower levels in the study group (p < 0.05). After treatment, the study group presented significantly higher albumin and prealbumin levels than the control group (p < 0.001). An obvious higher overall response rate was observed in the study group compared to the control group (p = 0.012). No significant inter-group discrepancy was found regarding the total incidence of adverse reactions (p = 0.752). Univariate analysis identified age, course of disease, heart rate (HR), Montreal Cognitive Assessment (MoCA) score, diastolic blood pressure (DBP), systolic blood pressure (SBP), drinking history, as well as medication regimen as risk factors impacting patient prognosis. Multivariate logistic regression analysis identified SBP, DBP, and medication regimen as the independent risk factors. Combined application of donepezil and nimodipine can effectively treat patients with comorbid CSVD and cognitive dysfunction. It can significantly lower the Hcy and hs-CRP levels and improve the nutritional status without increasing the frequency of adverse reactions. In addition, for CSVD patients with cognitive dysfunction, age, course of disease, MoCA score, HR, SBP, DBP, drinking history, and medication regimen are risk factors impacting patient prognosis, while SBP, DBP, and medication regimen are independent risk factors.

Untethered Microgrippers for Biopsy in the Upper Urinary Tract.

Untethered microrobots offer the possibility to perform medical interventions in anatomically complex and small regions in the body. Presently, it is necessary to access the upper urinary tract to diagnose and treat Upper Tract Urothelial Carcinoma (UTUC). Diagnostic and treatment challenges include ensuring adequate tissue sampling, accurately grading the disease, achieving completeness in endoscopic treatment, and consistently delivering medications to targeted sites. This work introduces microgrippers (µ-grippers) that are autonomously triggered by physiological temperature for biopsy in the upper urinary tract. The experiments demonstratedthat µ-grippers can be deployed using standard ureteral catheters and maneuvered using an external magnetic field. The μ-grippers successfully biopsied tissue samples from ex vivo pig ureters, indicating that the thin-film bilayer springs' autonomous, physiologically triggered actuation exerts enough force to retrieve urinary tract tissue. The quality of these biopsy samples is sufficient for histopathological examination, including hematoxylin and eosin (H&E) and GATA3 immunohistochemical staining. Beyond biopsy applications, the µ-grippers' small size, wafer-scale fabrication, and multifunctionality suggest their potential for statistical sampling in the urinary tract. Experimental dataand clinical reports underscore this potential through statistical simulations that compare the efficacy of µ-grippers with conventional tools, such as ureteroscopic forceps and baskets.

Circ_0002722-induced regulation of YAP promotes platinum resistance in oral squamous cell carcinoma: Implications for verteporfin therapy

Oral squamous cell carcinoma (OSCC) poses a significant public health burden due to its high prevalence and poor prognosis. Platinum resistance is one of the major challenges in OSCC treatment. Yes-associated protein (YAP) has been identified as a pivotal player in OSCC tumorigenesis and progression. Circular RNA (circRNA) has been implicated in chemoresistance in various cancers by regulation the function of microRNA. Nevertheless, the specific mechanisms linking circRNA to YAP expression in OSCC remain poorly understood. In this study, we detected the YAP and circRNA hsa_circ_0002722 (circ_0002722) expression by western blot (WB) and quantitative polymerase chain reaction (qPCR). We found that YAP and circ_0002722 were up-regulated in platinum resistance in OSCC tissues. Furthermore, transfection of circ_0002722 siRNA into platinum-resistant cells revealed that circ_0002722 acted as a regulator of miR-1305, which influenced YAP expression and thereby affected platinum sensitivity. In vivo experiments corroborated the synergistic effects of cisplatin and verteporfin (a YAP inhibitor) in combating platinum resistance. Targeting YAP emerges as a promising therapeutic strategy for addressing platinum resistance in OSCC, with circ_0002722 serving as a potential therapy target and valuable diagnostic marker. These findings shed light on the underlying mechanisms of platinum resistance, paving the way for the development of effective treatment approaches.

AB043. BRD4 promotes immune escape of glioma cells by upregulating PD-L1 expression.

Glioblastoma multiforme (GBM) poses significant challenges in treatment due to its aggressive nature and immune escape mechanisms. Despite recent advances in immune checkpoint blockade therapies, GBM prognosis remains poor. The role of bromodomain and extraterminal domain protein 4 (BRD4) in GBM, especially its interaction with immune checkpoints, is not well understood. Bioinformatic gene expression and survival analysis for BRD4 was utilized in The Cancer Genome Atlas (TCGA) and Chinese Glioma Genome Atlas (CGGA) databases. Clone formation assay, Transwell, Cell Counting Kit-8 (CCK8), and wound healing assay were utilized to validate BRD4's promotion of glioma cell proliferation, invasion, and migration. Chromatin immunoprecipitation (ChIP) assay was conducted to confirm BRD4 binding to the programmed death ligand 1 (PD-L1) promoter. A co-culture model was utilized with activated cluster of differentiation 8 (CD8)+ T cells and glioma cells. GL261 cells with BRD4 short hairpin RNA (shRNA) and/or PD-L1 cDNA were intracranially injected into mice to investigate tumor growth and survival time. Tumor tissue characteristics were analyzed using hematoxylin-eosin (H&E) and immunohistochemistry (IHC) staining and immune cell infiltration were assessed by flow cytometry. Bioinformatics analyses reveal elevated BRD4 expression in high-grade gliomas, correlating with poor patient survival. In vitro studies confirm that BRD4 promotes proliferation, invasion, and migration in GBM cells. BRD4 is a regulator of PD-L1 at the transcriptional level, implying its involvement in GBM's immune escape mechanisms. Co-culture experiments with CD8+ T cells demonstrate that BRD4 inhibition enhances tumor cell apoptosis. In vivo studies indicate that BRD4 knockout reduces immunosuppression, improves prognosis. Simultaneous manipulation of BRD4 and PD-L1 levels provides insights into their intertwined roles in shaping the immune landscape of GBM. BRD4 has the capability to regulate the growth of glioblastoma and enhance immune suppression by promoting PD-L1 expression. Targeting BRD4 represents a promising direction for future research and treatment.

Anterior choroidal artery aneurysms: a systematic review and meta-analysis of outcomes and ischemic complications following surgical and endovascular treatment.

Anterior choroidal artery (AChA) aneurysms account for 2%-5% of all intracranial aneurysms. Treatment considerations include microsurgical clipping, flow diversion, or coiling with or without adjunctive devices. AChA aneurysms pose challenges in treatment due to the origination of the aneurysm from the origin or proximal segment of the AChA. The AChA is particularly susceptible to vasospasm and occlusion during treatment with devastating neurological deficits, including hemiparesis, hemianesthesia, lethargy, neglect, and hemianopia. In this study, the authors performed a meta-analysis to quantify the outcomes and complication rates across treatment modalities for AChA aneurysms and to identify risk factors reported in the literature. The authors performed a systematic review of AChA aneurysms treated with surgical clipping, endovascular coiling, or flow diversion and reported in the PubMed, Embase, Scopus, and Cochrane search databases. Single-arm meta-analyses of the selected outcomes were performed in RStudio. Literature review yielded 25 studies that met the inclusion criteria. In total, 1627 patients were included in the analysis, with 554 males, 1009 females, and 64 unspecified. The rate of any complication in the full cohort was 11.6%, with a rate of ischemic complications of 5.5% and a favorable recovery rate of 90.3% of all patients treated. In total, 1064 patients underwent surgical clipping, 443 were treated with coiling, and 120 patients with flow diversion. In clipped patients, the rate of total surgical complications was 17.6%, with an ischemic complication rate of 9.4%. The rate of good functional recovery, defined on the basis of a Glasgow Outcome Scale score of 4-5 or modified Rankin Scale score of 0-2, was 88.0%, and complete obliteration was achieved in 84.5% of surgically clipped aneurysms. The complication rate in coiled patients was 10.3%, with an ischemic complication rate of 3.0%. Good functional recovery was achieved in 88.6% of coiled patients and complete aneurysm obliteration in 74.1%. Flow diversion resulted in a complication rate of 1.3%, with 0.7% rate of ischemic complications. Good functional recovery was achieved in 98.4% of patients and complete aneurysm obliteration in 79.0% in the flow diversion group. Aneurysm morphological features that impacted the complication rate were also identified to augment quantitative data and to help guide treatment selection for AChA aneurysms. Flow diversion showed significantly lower total and ischemic complications and improved outcomes compared to clipping and coiling. There may be differences in outcomes between treatment types, especially when considering the varied patient presentations that guide treatment selection.

AB002. DNA methylation-regulated genes contribute to temozolomide (TMZ) resistance by scaffolding paraspeckle proteins.

Temozolomide (TMZ) resistance in glioblastoma (GBM) remains a challenge in clinical treatment and the mechanism is largely unknown. Emerging evidence shows that epigenetic modifications including DNA methylation and non-coding RNA were involved in diverse biological processes, including therapeutic resistance. However, the underlying mechanisms by which DNA methylation-mediated non-coding RNA regulates TMZ resistance remain poorly characterized. RNA microarray and DNA methylation chips of TMZ-resistant and parental GBM cells were performed for the gain of unreported long non-coding RNA HSD52. Quantitative reverse transcription polymerase chain reaction (PCR) and fluorescence in situ hybridization assays were used to detect HSD52 levels in GBM cells and tissues. The investigation into HSD52's impact on TMZ resistance was conducted utilizing both in vitro assays and intracranial xenograft mouse models. The mechanism of HSD52 expression and its relationships with paraspeckle proteins, non-POU domain-containing octamer-binding protein (NONO) and splicing factor proline/glutamine rich (SFPQ), as well as alpha-thalassemia mental retardation X-linked (ATRX) mRNA were determined by pyrosequencing assay, chromatin immunoprecipitation, chromatin isolation by RNA purification, RNA immunoprecipitation, RNA pulldown, immunofluorescence, and western blot assays. HSD52 was highly expressed in high-grade glioma and TMZ-resistant GBM cells. Phosphorylated p38 mitogen-activated protein kinase (p38 MAPK)/ubiquitin specific peptidase 7 (USP7) axis mediates H3 ubiquitination, impairs the interaction between H3K23ub and DNA methyltransferase 1 (DNMT1) and the recruitment of DNMT1 at the HSD52 promoter to attenuate DNA methylation, which makes the transcription factor 12 (TCF12) more accessible to the promoter region to regulate HSD52 expression. Further analysis showed that HSD52 can serve as a scaffold to promote the interaction between NONO and SFPQ, and then increase the paraspeckle assembly and activate the paraspeckle/ataxia telangiectasia mutated (ATM) kinase pathway in GBM cells. In addition, HSD52 forms an RNA-RNA duplex with ATRX mRNA, and facilitates the association of heteromer of SFPQ and NONO with RNA duplex, thus leading to the increase of ATRX mRNA stability and level. In clinical patients, HSD52 is required for TMZ resistance and GBM recurrence. Our results reveal that HSD52 in GBM could serve as a therapeutic target to overcome TMZ resistance, enhancing the clinical benefits of TMZ chemotherapy.

Buoyancy-Assisted Fabrication of Liquid Diode: Janus Nanofibrous Membrane for Efficient Wastewater Treatment.

The pressing need for effective methods to separate oil and water in oily wastewater has spurred the development of innovative solutions. This work presents the creation and evaluation of a Janus nanofibrous membrane, also known as the Liquid Diode, developed using electrospinning (e-spinning) and buoyancy-assisted hydrothermal techniques. The membrane features a unique structure: one side is composed of PVDF nanofibers embedded with a GO/TiO2 composite, exhibiting in-air superhydrophobic and superoleophilic properties, while the reverse side consists of PVDF nanofibers with a ZnO nanorod array, demonstrating in-air superhydrophilic and underwater (UW) superoleophobic properties. This distinct asymmetric wettability enables the membrane to effectively separate both water-in-oil (w-in-o) and oil-in-water (o-in-w) emulsions, achieving an impressive liquid flux and separation efficiency (SEff). The in-air superhydrophobic side of the Janus nanofibrous membrane achieves a maximum oil flux (Fo) of 3506 ± 250 L m-2 h-1, while the in-air superhydrophilic side achieves a maximum water flux (Fw) of 1837 ± 150 L m-2 h-1, with SEff exceeding 98% for both sides. Furthermore, the Janus nanofibrous membrane maintained reliable mechanical stability after 10 cycles of sandpaper abrasion test and demonstrated excellent chemical stability when subjected to acidic, alkaline, cold water and hot water conditions for 24 h. These properties, combined with its ability in breaking down of organic contaminants (98% ± 2% in 210 min) and pharmaceutical contaminants (97% ± 2% in 210 min) under visible light, highlight its photocatalytic potential. Additionally, the membrane's antifouling and antibacterial properties suggest long-term and sustainable use in wastewater treatment applications. The synergistic combination of these superior properties positions the Janus nanofibrous membrane as a promising solution for addressing complex challenges in wastewater treatment and environmental remediation.

Pharmaceutical inhibition of BCL6 ameliorates resistance to imatinib in chronic myeloid leukemia

The tyrosine kinase inhibitors (TKIs) have improved overall survival of CML (chronic myeloid leukemia) patients and allow them to experience normal life expectancy. However, relapse and drug resistance remain the main challenges in the clinical treatment of CML. The B-cell lymphoma 6 (BCL6) is essential to regulation of multiple function such as immune response and lymphomagenesis in lymph node germinal cells. Recent studies have shown that BCL6 is required for the maintenance of leukemia stem cells in CML, but the expression of Bcl-6 in response to Imatinib and the underlying mechanism are still unclear. Here, we found that BCL6 is expressed at high levels in primary CML bone marrow samples and CML TKI-resistance cell lines. CML cells with higher levels of BCL6 were generally sensitive to treatment with BCL6 inhibitors, BI-3812. Treatment of CML cells with BCL6 inhibitor and TKIs suggested enhanced anti-leukemia activity. In summary, our findings suggest BCL6 as a therapeutic target for the treatment of CML.

AB045. E2F6 promotes temozolomide resistance in glioblastoma by enrichment in CARD6 and POSTN promoter region.

Glioblastoma (GBM) is the most aggressive primary malignant brain tumor. Temozolomide (TMZ) is the most used first-line chemotherapeutic agent for GBM after surgery, but acquired resistance to TMZ frequently leads to treatment failure and is a major challenge in the clinical treatment of GBM. Increasing evidence suggests that E2F transcription factor 6 (E2F6) is associated with a variety of tumor malignant biological behaviors and drug resistance, but its biological function and underlying molecular mechanisms in GBM are unknown. The study investigated the levels of E2F6 in both TMZ-sensitive and TMZ-resistant GBM cells and tissues using Western blotting and immunofluorescence assays. In vitro experiments were conducted to explore the impact of E2F6 on TMZ resistance and glioma stem cell stemness. These experiments included Western blotting, colony formation assay, flow cytometry assay, and TdT-mediated dUTP nick-end labeling (TUNEL) assay. Bioinformatic analyses were conducted to investigate the mechanism behind the high expression of E2F6 in TMZ-resistant cells and its correlation with caspase recruitment domain 6 (CARD6) and disulfide-linked cell adhesion protein (POSTN). The study employed bioinformatic analyses, messenger RNA (mRNA) sequencing, chromatin immunoprecipitation sequencing assay, immunofluorescence, quantitative real-time polymerase chain reaction (qRT-PCR), and Western blotting. To examine the function of E2F6, an intracranial xenograft tumor mouse model was used for in vivo experiments. It was found that CARD6 and POSTN were significantly associated with TMZ resistance and survival of GBM patients. E2F6 was up-regulated in TMZ-resistant cells and tissues. Knockdown of E2F6 down-regulated the expression of CARD6, promoted TMZ-induced apoptosis, and enhanced chemo-sensitivity, whereas its overexpression significantly increased TMZ resistance in vitro and in vivo. In addition, E2F6 can promote TMZ resistance through stem-like properties acquisition. We identified a signaling pathway related to E2F6 and POSTN, which maintains the self-renewal of GBM stem cells (GSCs). E2F6 concentrates in the promoter region of POSTN, thereby regulating the expression of GSCs-related genes cluster of differentiation 133 (CD133), Nestin, and sex-determining region Y-box 2 (SOX2), which may be involved in tumor metabolism and drug resistance processes. Down-regulation of E2F6 down-regulated the expression of POSTN and inhibited tumor growth in nude mice. These results suggest that the E2F6-CARD6/POSTN signaling axis regulates the malignant biological behaviors of GBM and TMZ resistance. These findings are expected to provide promising therapeutic targets for CARD6 overcoming GBM TMZ resistance.

Dynamically visualizing profibrotic maladaptive repair after acute kidney injury by fibroblast activation protein imaging

A major challenge in prevention and early treatment of organ fibrosis is the lack of valuable tools to assess the evolving profibrotic maladaptive repair after injury invivo in a non-invasive way. Here, using acute kidney injury (AKI) as an example, we tested the utility of fibroblast activation protein (FAP) imaging for dynamic assessment of maladaptive repair after injury. The temporospatial pattern of kidney FAP expression after injury was first characterized. Single-cell RNA sequencing and immunostaining analysis of patient biopsies were combined to show that FAP was specifically upregulated in kidney fibroblasts after AKI and was associated with fibroblast activation and chronic kidney disease (CKD) progression. This was corroborated in AKI mouse models, where a sustained and exaggerated kidney FAP upregulation was coupled to persistent fibroblast activation and a fibrotic outcome, linking kidney FAP level to post-insult maladaptive repair. Furthermore, using positron emission tomography (PET)/CT scanning with FAP-inhibitor tracers ([18F]FAPI-42, [18F]FAPT) targeting FAP, we demonstrated the feasibility of non-invasively tracking of maladaptive repair evolution toward kidney fibrosis. Importantly, a sustained increase in kidney [18F]FAPT (less hepatobiliary metabolized than [18F]FAPI-42) uptake reflected persistent kidney upregulation of FAP and characterized maladaptive repair after AKI. Kidney [18F]FAPT uptake at hour 2-day 7 correlated with kidney fibrosis 14 days after AKI. Similar changes in [18F]FAPI-42 PET/CT imaging were observed in patients with AKI and CKD progression. Thus, persistent kidney FAP upregulation after AKI was associated with maladaptive repair and a fibrotic outcome. Hence, FAP-specific PET/CT imaging enables dynamic visualization of maladaptive repair after AKI and prediction of kidney fibrosis within a clinically actionable window.

Electro-activated persulfate degradation of chlorophene (CP): Kinetics, mechanisms and theoretical calculations

BackgroundActivation of persulfate (PS) to generate sulphate radicals is an effective method to remove organic pollutants from water. However, conventional methods still face challenges in efficient wastewater treatment due to the need to add additional reagents. MethodsDegradation of chlorophene (4-chloro-2-(phenylmethyl)phenol, CP) by activation of PS through electro-activation. Comprehensive experimental and product toxicity results showed that Electro-PS is an environmentally friendly and effective method for removing pollutants from water. Significant findingsWhen the pH value was 7.0, the current density and PS concentration were 10 mA/cm2 and 1.0 mM, respectively, the removal rate of CP reaches 90.1 % within 10 min. The presence of humic acid (HA), NO3−, and HCO3− may deplete the active substance and thus inhibit the degradation of CP. On the contrary, Cl− could promote CP degradation due to the generation of Cl•. The EPR results indicated that SO4•−, •OH, 1O2, and O2•− contributed to the degradation of CP, and the quenching experiments proved their contributions to be 40.6 %, 24.9 %, 11.3 % and 7.5 %, respectively. The main types of oxidation products of CP in the Electro-PS system were identified and oxidation pathways were determined by mass spectrometry, and the product structures were verified by theoretical calculations. Evaluation by the ECOSAR software showed that the toxicity of CP oxidation products was reduced.

Pulmonary benign metastasizing leiomyoma presenting as acute hypoxemic respiratory failure: a case report

Pulmonary benign metastasizing leiomyoma is an uncommon condition, predominantly affecting women of childbearing age with a history of uterine smooth muscle tumors and uterine leiomyoma surgery for uterine leiomyoma. The progression of PBML is often unpredictable and depends on the extent of lung involvement. Generally, most patients remain asymptomatic, but a minority may experience coughing, wheezing, or shortness of breath, which are frequently misdiagnosed as pneumonia. consequently, this presents significant challenges in both treatment and nursing care before diagnosis. This paper reports the case of a 35-year-old woman primarily diagnosed with acute hypoxic respiratory failure who was transferred from the emergency room to the intensive care unit. The initial computed tomography scan of the patient’s lungs indicated diffuse interstitial pneumonia, but the sequencing of the alveolar lavage fluid pathogen macro did not detect any bacteria, fungi, or viruses. Moreover, the patient remained in a persistent hypoxic state before the definitive diagnosis. Therefore, our focus was on maintaining the airway patency of the patient, using prone ventilation, inhaling nitric oxide, monitoring electrical impedance tomography, and preventing ventilator-associated pneumonia to improve oxygenation, while awaiting immunohistochemical staining of the patient’s biopsied lung tissue. This would help us clarify the diagnosis and treat it based on etiology. After meticulous treatment and nursing care, the patient was weaned off the ventilator after 26 days and transferred to the respiratory ward after 40 days. This case study may serve as a reference for clinical practice and assist patients suffering from PBML.

Immunometabolic rewiring in macrophages for periodontitis treatment via nanoquercetin-mediated leverage of glycolysis and OXPHOS

Periodontitis is a chronic inflammatory disease marked by a dysregulated immune microenvironment, posing formidable challenges for effective treatment. The disease is characterized by an altered glucose metabolism in macrophages, specifically an increase in aerobic glycolysis, which is linked to heightened inflammatory responses. This suggests that targeting macrophage metabolism could offer a new therapeutic avenue. In this study, we developed an immunometabolic intervention using quercetin (Q) encapsulated in bioadhesive mesoporous polydopamine (Q@MPDA) to treat periodontitis. Our results demonstrated that Q@MPDA could reprogram inflammatory macrophages to an anti-inflammatory phenotype (i.e., from-M1-to-M2 repolarization). In a murine periodontitis model, locally administered Q@MPDA reduced the presence of inflammatory macrophages, and decreased the levels of inflammatory cytokines (IL-1β and TNF-α) and reactive oxygen species (ROS) in the periodontium. Consequently, it alleviated periodontitis symptoms, reduced alveolar bone loss, and promoted tissue repair. Furthermore, our study revealed that Q@MPDA could inhibit the glycolysis of inflammatory macrophages while enhancing oxidative phosphorylation (OXPHOS), facilitating the shift from M1 to M2 macrophage subtype. Our findings suggest that Q@MPDA is a promising treatment for periodontitis via immunometabolic rewiring.

IgA nephropathy: current treatment status, prospects, opportunities, and challenges

IgA nephropathy: current treatment status, prospects, opportunities, and challenges

Opportunities and Challenges in the Development of Antibody-Drug Conjugate for Triple-Negative Breast Cancer: The Diverse Choices and Changing Needs.

Triple-negative breast cancer (TNBC) is a highly heterogeneous breast cancer subtype, which is also characterized by the aggressive phenotype, high recurrence rate, and poor prognosis. Antibody-drug conjugate (ADC) is a monoclonal antibody with a cytotoxic payload connected by a linker. ADC is gaining more and more attention as a targeted anti-cancer agent. Clinical studies of emerging ADC drugs such as sacituzumab govitecan and trastuzumab deruxtecan in patients with metastatic breast cancer (including TNBC) are progressing rapidly. In view of its excellent clinical efficacy and good tolerability, Sacituzumab govitecan gained accelerated approval by the FDA for the treatment of advanced metastatic TNBC in 2020. This review discusses the treatment status and challenges in TNBC, with an emphasis on the current status of ADC development and clinical trials in TNBC and metastatic breast cancer. We also summarize the clinical experience and future exploration directions of ADC development for TNBC patients.

A Supramolecular Antibiotic Targeting Drug-Resistant Pseudomonas aeruginosa through the Inhibition of Virulence Factors and Activation of Acquired Immunity.

The bacterium Pseudomonas aeruginosa is an exceptionally resilient opportunistic pathogen, presenting formidable challenges for treatment due to its proclivity for developing drug resistance. To address this predicament, we have devised a self-assembled supramolecular antibiotic known as dHTSN1@pHPplus, which can circumvent the drug resistance mechanism of Pseudomonas aeruginosa and effectively combat Pseudomonas aeruginosa infection by impeding the secretion of key virulence factors through the inhibition of the type III secretion system while simultaneously mobilizing immune cells to eradicate Pseudomonas aeruginosa. Furthermore, dHTSN1@pHPplus was ingeniously engineered with infection-targeting capabilities, enabling it to selectively concentrate precisely at the site of infection. As anticipated, the administration of dHTSN1@pHPplus exhibited a remarkable therapeutic efficacy in combating dual resistance to Meropenem and imipenem in a mouse model of P. aeruginosa lung infection. The results obtained from metagenomic detection further confirmed these findings, demonstrating a significant reduction in the proportion of Pseudomonas aeruginosa compared to untreated mice with Pseudomonas aeruginosa-infected lungs. Additionally, no notable acute toxicity was observed in the acute toxicity experiments. The present study concludes that the remarkable efficacy of dHTSN1@pHPplus in treating drug-resistant P. aeruginosa infection confirms its immense potential as a groundbreaking antibiotic agent for combating drug-resistant P. aeruginosa.

Molecular typing of reduced susceptibility of Acinetobacter calcoaceticus-baumannii complex to Chlorhexidine in Turkey by pulsed-field gel electrophoresis.

Introduction. The global spread of Acinetobacter spp., particularly the Acinetobacter calcoaceticusbaumannii (ACB) complex, has led to its recognition as a significant pathogen by the World Health Organization (WHO). The increasing resistance of the ACB complex to multiple antibiotics presents a challenge for treatment, necessitating accurate antibiotic susceptibility profiling after isolation.Hypothesis or gap statement. There is limited understanding of the antimicrobial resistance and chlorhexidine, a biocide, susceptibility profiles of ACB complex strains, especially in clinical settings in Turkey.Aim. This study aimed to identify ACB complex strains recovered from various clinical specimens at Hacettepe University Hospitals in Ankara, Turkey, in 2019, and to assess identification, their antibiotic and chlorhexidine susceptibility profiles, and genomic relatedness.Methodology. Eighty-two ACB complex strains were identified using MALDI-TOF MS. Susceptibility testing to 12 antibiotics was conducted using the disc diffusion method, and colistin, chlorhexidine susceptibility was assessed using the broth microdilution technique, following the latest EUCAST and CLSI guidelines. ACB complex members with reduced chlorhexidine sensitivity were further analyzed by pulsed-field gel electrophoresis (PFGE) for bacterial typing.Results. Among the isolates, 1.2% were multidrug-resistant (MDR), 73.2% were extensively drug-resistant (XDR), and 12.2% were pandrug-resistant (PDR). Carbapenem resistance was found in 86.7% of MDR, PDR, and XDR strains. Colistin resistance was observed in 15.8% of isolates, and 18.2% exhibited decreased susceptibility to chlorhexidine. PFGE revealed seven different clones among strains with reduced chlorhexidine sensitivity, indicating vertical transmission within the hospital.Conclusion. This study highlights the reduced susceptibility to chlorhexidine in ACB complex members and provides epidemiological insights into their spread. The findings underscore the importance of screening for antimicrobial resistance and biocide susceptibility profiles to effectively manage healthcare-associated infections.