Treatment Challenges Research Articles

Cr3+doped α-Fe2O3 nanoparticles for photodegradation of organic pollutants with their disinfection efficacy

Pristine and Cr-doped α-Fe2O3 nanoparticles were synthesized using a low-cost and simple one-step hydrothermal method without any precipitating agent. Cr-doped α-Fe2O3 was found to be a promising candidate for recyclable photocatalytic application for Tetracycline (TC) and Congo-red (CR) degradation under normal sunlight irradiation along with excellent antibacterial properties. Addition of Cr shows a significantly improved degradation efficiency from 20% to 91% in just 25 min for CR, while the degradation rate reached to 81% for TC, which was also monitored in real-time using internet of things (IoT). Also, a high degree of mineralization was achieved (∼87.9%), which was confirmed using total organic carbon (TOC) content. In parallel, the biochemical oxygen demand/chemical oxygen demand (BOD5/COD) ratio confirmed the fast degradation efficiency using a small amount of catalytic dosage (∼ 0.40 g/L). Also, degradation of multiple dyes provides a promising avenue for addressing complex waste water treatment challenges. Moreover, Cr-doped α-Fe2O3 displays excellent antibacterial activity towards E.coli and E.Faecium. Major factors involved in sunlight driven photocatalytic activity for example absorbance range, porosity, separation between e--h+, and charge transfer property were surprisingly improved by Cr doping and henceforth increased photocatalytic activity and antibacterial properties. This work highlights the potential utilization of Cr-doped α-Fe2O3 for the purification and disinfection of industrial waste water.

Enhanced antitumor activity of lapatinib against triple-negative breast cancer via loading in human serum albumin

Triple-negative breast cancer (TNBC) presents significant treatment challenges due to its aggressive nature. Human serum albumin (HSA) is a promising drug delivery platform, offering high binding capacity, biocompatibility, and reduced toxicity. Lapatinib (LAP), a tyrosine kinase inhibitor for TNBC, is hindered by poor water solubility and toxicity. To address these issues, LAP was encapsulated within HSA (HSA-LAP), and its structural, drug release, and therapeutic properties were evaluated in cellular and animal TNBC models. HSA-LAP demonstrated efficient drug loading and pH-dependent tumor-targeted release, favoring acidic tumor microenvironments. Structural and microscopic studies confirmed LAP binding to HSA, with only minor structural and no significant morphological changes observed. In 4 T1 breast cancer cells, HSA-LAP exhibited superior anti-proliferative, pro-apoptotic, and anti-migratory effects compared to free LAP, which were further amplified when combined with VGB3, a VEGFR1/2-targeting peptide, indicating an effective dual-targeting strategy for TNBC. In vivo, HSA-LAP showed greater tumor inhibition and improved survival rates, especially in combination with VGB3 through apoptosis induction. Biodistribution studies using technetium-99 m (99mTc) labeling revealed enhanced tumor targeting. These findings highlight the potential of HSA as a delivery vehicle for LAP, particularly in combination with anti-angiogenic agents like VGB3, offering a promising therapeutic strategy for TNBC.

Understanding and managing locally advanced basal cell carcinoma: insights into pathogenesis, therapeutic strategies, and the role of hedgehog pathway inhibitors.

Understanding and managing locally advanced basal cell carcinoma (BCC) is crucial given its substantial prevalence and potential for local tissue destruction. While BCC typically exhibits low metastatic potential, its high incidence underscores the need for enhanced therapeutic strategies. Locally advanced BCC presents unique challenges, often necessitating aggressive interventions to prevent disfigurement and functional impairment. The emergence of hedgehog pathway inhibitors (HHIs) offers promising therapeutic avenues by targeting aberrant hedgehog signaling, a key driver in BCC pathogenesis. Thus, elucidating the pathogenesis of locally advanced BCC and exploring the role of HHIs are critical endeavors in effectively managing this prevalent carcinoma. Epidemiologically, BCC primarily affects individuals with fair skin and chronic sun exposure, with an increasing incidence noted among younger age groups. Risk factors include UV radiation exposure, familial history of skin cancer, immunosuppression, and genetic syndromes such as basal cell nevus syndrome and xeroderma pigmentosum. Pathogenetically, BCC arises from cells in the skin's epidermis, with hedgehog pathway activation being a primary genetic driver, involving mutations in PTCH1 and SMO. Resistance to hedgehog inhibitors may occur due to genetic changes, complicating treatment strategies. BCC is characterized by low immunogenicity, which hinders immune response and contributes to treatment challenges. Enhanced understanding of the epidemiology, risk factors, and pathogenesis of locally advanced BCC, along with the development of targeted therapeutic approaches such as hedgehog pathway inhibitors, is essential for effectively managing this prevalent carcinoma and improving patient outcomes.

Comparative Analysis of Platelet-rich Plasma and Triamcinolone Acetonide Injections in the Management of Plantar Fasciitis: A Prospective Study

Abstract Context: Plantar fasciitis, a prevalent cause of heel pain, poses challenges in treatment due to diverse therapeutic options and variable outcomes. Platelet-rich plasma (PRP) and triamcinolone acetonide (TA) injections have emerged as potential interventions, yet their comparative effectiveness remains debated. Aims: The aim of the study was to compare the effectiveness of PRP and TA injections in relieving pain, improving function, and promoting healing in individuals with plantar fasciitis. Settings and Design: The study design was a prospective, hospital-based, experimental study. Subjects and Methods: A 2-year prospective hospital-based experimental study was conducted, enrolling patients aged 30–60 years with plantar fasciitis. Patients received either PRP or TA injections. Preoperative assessments and 3 months of monitoring were performed. Foot and Ankle Outcome Score (FAOS) survey was utilized for outcome evaluation. Statistical Analysis Used: T-test was applied. Results: Ninety patients were included, with both treatment groups demonstrating significant improvement in foot symptoms. PRP administration showed superiority in descending and ascending stairs, rising from sitting, and walking on flat surfaces compared to TA. FAOS scores indicated significant improvement posttreatment in both groups, with PRP yielding better outcomes than TA. Conclusions: Both PRP and TA injections effectively alleviate foot symptoms in plantar fasciitis patients. However, PRP demonstrates superior outcomes in specific functional activities and quality-of-life components compared to TA. These findings suggest PRP as a preferred intervention in the management of plantar fasciitis.

Biofilm Production Activity and Antibiotics Susceptibility of Streptococcus mutans Isolates from Patients with Dental Caries

Dental caries, a prevalent chronic infectious ailment, commences with the adherence of cariogenic bacteria to the teeth, particularly Streptococcus mutans. These microorganisms utilize sugars to produce acid, resulting in the gradual demineralization of the dental structure. Streptococcus mutans a gram positive bacterium is found to play the most significant role in the dental caries in terms of being the earliest colonizer in the formation of caries. The current research focuses on the isolation and identification of the Streptococcus mutans pathogen in individuals affected by dental caries. The isolated strains were cultured on specific media, with one hundred samples of dental caries obtained from human teeth. Among these samples, fifty were identified as positive bacterial isolates utilizing MS-agar (Mitist Salivares agar), with ten isolates categorized under the group Streptococci and twenty isolates identified as S. mutans. Identification of bacterial isolates was carried out based on morphological and cultural characteristics, biochemical tests, and VITEK-II. Additionally, an antibiogram assay was conducted to assess the susceptibility and resistance of the pathogen to various drugs. The findings revealed that all locally isolated S. mutans strains displayed 100% resistance to Cefepime, while showing different levels of resistance and susceptibility to other antibiotics such as Doxycycline, Amoxicillin-clavulanic acid, Trimethoprim-sulfamethoxazole, Vancomycin, Tetracycline, Ampicillin, and Meropenem. In this study, ELISA was employed to differentiate between Streptococcus. mutans isolates that produced biofilms and those that did not by utilizing the optical density at 630 nm. Bacterial biofilms contribute to chronic diseases that pose challenges in treatment. Twenty distinct isolates were evaluated for their biofilm-forming capabilities, with 9 (45%) identified as strong biofilm producers, 7 (35%) classified as moderate biofilm producers, and 4 (20%) categorized as weak biofilm producers

Robust antifouling Poly(ionic liquid)s membrane with cyclodextrin skeleton for separation of oil/water emulsions

Membrane fouling remains a persistent and arduous challenge in the industrial treatment of different surfactants-stabilized oily wastewater. Constructing a robust antifouling and sustainable hydration coating on the membrane surface to efficiently repel oils or surfactants is a critical requirement. Herein, cyclodextrin-based poly(ionic liquid)s (PILs) coatings are cross-linked via the co-deposition on poly(vinylidene fluoride) (PVDF) of quaternized heptkis(6-deoxy-6-vinylimidazolium)-β-cyclodextrin (CD-Vi) derivatives as skeleton and acrylic acid (AA) monomers, and following one-step free radical photopolymerization. Combining with the strong hydration of the CD-based PILs coating, the resultant membrane exhibits fabulous superhydrophilicity and underwater superoleophobicity, oil repulsion, and self-cleaning capability. It demonstrates robust mechanical durability and chemical stability in harsh environments without losing its superhydrophilicity. Besides, the PIL-CD/AA coating can separate various surfactant-free and different surfactants (cationic CTAB, anionic SDS, and nonionic TWEEN 80) stabilized oil / water emulsions. During the long-term cycle operations, it also realizes stable recyclability with a series of permeation fluxes as high as removal efficiencies (>99.6 %) after 20 cycles for surfactant-free cyclohexane-in-water emulsion and 10 cycles for CTAB-stabilized isooctane-in-water emulsion.

Recent Challenges in Diagnosis and Treatment of Invasive Candidiasis in Neonates.

Invasive Candida infections represent a significant cause of morbidity and mortality in the neonatal intensive care unit (NICU), particularly among preterm and low birth weight neonates. The nonspecific clinical presentation of invasive candidiasis, resembling that of bacterial sepsis with multiorgan involvement, makes the diagnosis challenging. Given the atypical clinical presentation and the potential detrimental effects of delayed treatment, empirical treatment is often initiated in cases with high clinical suspicion. This underscores the need to develop alternative laboratory methods other than cultures, which are known to have low sensitivity and a prolonged detection time, to optimize therapeutic strategies. Serum biomarkers, including mannan antigen/anti-mannan antibody and 1,3-β-D-glucan (BDG), both components of the yeast cell wall, a nano-diagnostic method utilizing T2 magnetic resonance, and Candida DNA detection by PCR-based techniques have been investigated as adjuncts to body fluid cultures and have shown promising results in improving diagnostic efficacy and shortening detection time in neonatal populations. This review aims to provide an overview of the diagnostic tools and the current management strategies for invasive candidiasis in neonates. Timely and accurate diagnosis followed by targeted antifungal treatment can significantly improve the survival and outcome of neonates affected by Candida species.

MiR-21 and miR-145 as Prognostic Biomarkers for Radiotherapy Responses in Cervical Cancer Patients: A Preliminary Study.

Radioresistance poses a significant challenge in the effective treatment of cervical cancer, often leading to poor patient outcomes. MicroRNA-21 (miR-21) and MicroRNA-145 (miR-145) are oncogenic micro-RNAs associated with various cancers, including cervical cancer, but their potential as predictive biomarkers for radioresistance remains underexplored. This study aimed to investigate the association between miR-21 and miR-145 expressions and the response to radiation therapy in cervical cancer patients. An analytical cross-sectional study was conducted on 140 subjects with cervical cancer stages IIIB and IVA who received definitive radiotherapy. miR-21 and miR-145 expressions were measured using real-time reverse transcriptase-polymerase chain reaction (RT-qPCR). A total of 102 subjects (72.9%) were classified as having stage III cervical cancer, and 38 subjects (27.1%) were classified as having stage IV cervical cancer. Disease progression occurred in 60.7% of subjects. The cut-off value for miR-21 expression was 0.00088 nmol/(mg/mL) (AUC 0.676, sensitivity 70.8%, specificity 50.8%), and a higher expression was significantly associated with radioresistance (p = 0.010). miR-145, with a cut-off of 0.0239 nmol/(mg/mL) (AUC 0.612, sensitivity 67.5%, specificity 45.5%), showed no significant association with treatment response (p = 0.132). Combining miR-21 and miR-145 (AUC 0.639, sensitivity 68.6%, specificity 46.9%, p = 0.063) did not significantly improve the predictive accuracy. This study suggests that an elevated miR-21 expression is significantly associated with radioresistance in cervical cancer patients, while miR-145 expression shows no significant correlation with treatment response. Additionally, combining miR-21 and miR-145 does not enhance the predictive power.

From genes to populations: developing precision medicine for acral lentiginous melanoma through in silico and epidemiological studies

Acral Lentiginous Melanoma (ALM) is a rare and aggressive form of melanoma that predominantly affects individuals with darker skin tones, posing significant challenges in both diagnosis and treatment. The growing demand for more personalized and effective treatments has led to the exploration of innovative approaches to tackle these challenges. This study integrates in silico drug design with comprehensive statistical analysis to identify and validate therapeutic targets specific to ALM. Key genes such as PLD1, CDKN2A, KIT, TERT, and NRAS were identified using advanced bioinformatics tools like DisGeNET, PANTHER DB, Network Analyst, and STRING DB. In parallel, a detailed demographic analysis involving 248 patients was conducted using SPSS, shedding light on factors influencing knowledge and awareness of ALM within affected populations. The findings from this dual approach emphasize the critical need for tailored therapeutic strategies that account for both genetic factors and patient demographics. The projected increase in ALM cases and the associated need for targeted therapies underscore the importance of continuing research into specialized treatments that can address the unique characteristics of this melanoma subtype. By advancing our understanding of ALM’s genetic profile and epidemiology, this study lays the foundation for the development of precision medicine solutions that could significantly improve patient outcomes and overall management of this aggressive disease.

Adrenocorticotropic hormone: Therapeutic use and effects in nephrotic syndrome

Background: NS is defined by the presence of significant proteinuria, which leads to low levels of albumin in the blood and the development of edema. This occurs as a result of damage to the glomerular filtration barrier. Corticosteroids are the main therapeutic approach for NS. Prolonged usage of steroids can result in numerous side effects, including steroid resistant NS, which poses a difficult challenge for treatment and can cause substantial morbidity and mortality. Although efforts have been made to decrease the use of steroids by employing non-steroidal immunosuppressive drugs for rapid recovery, these treatments have also exhibited adverse consequences. These difficulties have prompted the notion of utilizing ACTH in these situations. Objective: This study seeks to analyze the efficacy of ACTH by thoroughly examining its mechanism and comparing it to conventional treatment for NS. Summary and important messages: The study demonstrates that ACTH has the potential to not only decrease protein loss but also reduce the occurrence of relapses and the amount of glucosteroids required. This suggests that ACTH could be a viable treatment alternative. The exact mechanism is currently unidentified, while the MCR1 agonism linked to ACTH suggest a renoprotective mechanism that is beneficial in NS. A comprehensive analysis using a large-scale randomized controlled trial is necessary to fully comprehend the effectiveness and safety profile of ACTH in improving the quality of care for patients.

Evaluation of gradient strip diffusion for susceptibility testing of aztreonam-avibactam in metallo-β-lactamase-producing Enterobacterales.

The emergence of metallo-β-lactamase (MBL)-producing Enterobacterales presents unique clinical treatment challenges. Recently developed β-lactam/ β-lactamase inhibitor combination agents, while effective against other carbapenemase-producing organisms, are notably ineffective against MBL producers. While MBLs do not hydrolyze monobactams (aztreonam), many MBL-producing organisms are resistant to aztreonam through alternate mechanisms, leaving cefiderocol as the sole monotherapy treatment option recommended for MBL producers. Recent guidelines for the treatment of MBL-harboring organisms have added combination therapy with aztreonam and ceftazidime-avibactam, using ceftazidime-avibactam as a source of the β-lactamase inhibitor avibactam. Current laboratory testing options for the combination of aztreonam-avibactam are limited to broth microdilution (BMD) and broth disk elution (BDE) methods, which are not practical in most clinical laboratories. In this study, we evaluated the performance of aztreonam/avibactam gradient strips on 103 MBL-producing Enterobacterales patient isolates as well as an additional 31 isolates from the CDC AR Bank. All MBL Enterobacterales patient isolates included in this study harbored a New Delhi metallo-β-lactamase (blaNDM) gene. Essential agreement of gradient strip minimal inhibitory concentrations (MICs) for patient isolates compared to BMD was 93.2%. While there are no established breakpoints for aztreonam-avibactam, category agreement (CA) for patient isolates was 97.1% when using the CLSI aztreonam breakpoints. There were no major or very major errors observed. There were three minor errors. Precision for aztreonam-avibactam gradient strip diffusion was 100%. These data demonstrate that the use of gradient strip diffusion for aztreonam-avibactam MIC determination in MBL-producing Enterobacterales is a viable option for clinical laboratories.

Magnetic graphene oxide nanosheets with amidoamine dendronized crosslinks for dual pH and redox-sensitive doxorubicin delivery

Delivering anticancer drugs to the appropriate site within the body poses a critical challenge in cancer treatment with chemotherapeutic agents like doxorubicin (DOX). Magnetic graphene oxide (GO) nanosheets with generation 1 (G1) amidoamine-dendronized crosslinks were developed by coupling cystamine-functionalized GO nanosheets with Fe3O4 nanoparticles modified with primary amine and methyl acrylate. These magnetic GO nanosheets were loaded with DOX to create a dual pH- and redox-responsive delivery system for cancer chemotherapy. The prepared magnetic nanosheets underwent characterization using FTIR, XRD, DLS, VSM, FE-SEM, and TEM. Physical DOX adsorption was evaluated using various isotherms, including Langmuir, Freundlich, Temkin, and Dubinin-Radushkevich. The in-vitro release profiles of DOX from the magnetic nanosheets were studied under different pH conditions, with and without glutathione (GSH), and the drug release data were fitted with various kinetic models. Additionally, an MTT assay was employed to assess the compatibility and antitumor activity of DOX-loaded magnetic nanosheets in the HepG2 cell line. The results showed that the maximum drug loading was 13.1% (w/w) at a drug/carrier ratio of 1. Without GSH addition, the maximum drug release after 10 days was only 17.9% and 24.1% at pH 7.4 and 5.3, respectively. However, in the presence of GSH, the maximum drug release reached 51.7% and 64.8% at pH 7.4 and 5.3, respectively. Finally, the research findings suggest that the magnetic nanosheets exhibited pH- and redox-stimuli drug release, high biocompatibility, and superior antitumor activity compared to free DOX.

Identification of Anomalies in Lung and Colon Cancer Using Computer Vision-Based Swin Transformer with Ensemble Model on Histopathological Images.

Lung and colon cancer (LCC) is a dominant life-threatening disease that needs timely attention and precise diagnosis for efficient treatment. The conventional diagnostic techniques for LCC regularly encounter constraints in terms of efficiency and accuracy, thus causing challenges in primary recognition and treatment. Early diagnosis of the disease can immensely reduce the probability of death. In medical practice, the histopathological study of the tissue samples generally uses a classical model. Still, the automated devices that exploit artificial intelligence (AI) techniques produce efficient results in disease diagnosis. In histopathology, both machine learning (ML) and deep learning (DL) approaches can be deployed owing to their latent ability in analyzing and predicting physically accurate molecular phenotypes and microsatellite uncertainty. In this background, this study presents a novel technique called Lung and Colon Cancer using a Swin Transformer with an Ensemble Model on the Histopathological Images (LCCST-EMHI). The proposed LCCST-EMHI method focuses on designing a DL model for the diagnosis and classification of the LCC using histopathological images (HI). In order to achieve this, the LCCST-EMHI model utilizes the bilateral filtering (BF) technique to get rid of the noise. Further, the Swin Transformer (ST) model is also employed for the purpose of feature extraction. For the LCC detection and classification process, an ensemble deep learning classifier is used with three techniques: bidirectional long short-term memory with multi-head attention (BiLSTM-MHA), Double Deep Q-Network (DDQN), and sparse stacked autoencoder (SSAE). Eventually, the hyperparameter selection of the three DL models can be implemented utilizing the walrus optimization algorithm (WaOA) method. In order to illustrate the promising performance of the LCCST-EMHI approach, an extensive range of simulation analyses was conducted on a benchmark dataset. The experimentation results demonstrated the promising performance of the LCCST-EMHI approach over other recent methods.

Alcohol Use Disorder and Social Anxiety: A Clinical Study on Dual Pathology

This article explores the complex relationship between alcohol use disorder (AUD) and social anxiety disorder (SAD), two conditions that frequently co-occur in clinical practice. Studies indicate that individuals with SAD are at an increased risk of developing AUD, using alcohol as a means to alleviate anxiety in social situations. This dual pathology presents significant challenges in both diagnosis and treatment, as the presence of one disorder can exacerbate the other. Through a clinical case study and a comprehensive review of the literature, we aim to shed light on the mechanisms of this comorbidity, explore therapeutic approaches, and highlight the importance of integrated treatment strategies. The case of a 31-year-old patient with severe alcohol dependence and social anxiety illustrates the complexities of managing such cases, where both psychological and pharmacological interventions are required for successful outcomes.

Evaluating treatment practices and challenges in systemic Juvenile Idiopathic Arthritis: a comprehensive survey analysis

ObjectiveThis study aims to assess current diagnostic and management for systemic Juvenile Idiopathic Arthritis (sJIA) among physicians, evaluate the challenges encountered in diagnosis and treatment, and identify the educational needs and professional development engagements of physicians managing sJIA.MethodsA nationwide survey was conducted from November 2023 to March 2024 across tertiary and secondary pediatric and general hospitals in China. The survey targeted physicians with at least three years of specialty experience, resulting in 310 valid responses from 25 provinces, autonomous regions, and municipalities. The survey collected data on diagnostic practices, treatment approaches, and professional development related to sJIA. Data collection was facilitated through WeChat, and statistical analysis was performed using descriptive statistics. Ethical approval was obtained from the Ethics Committee of Beijing Children’s Hospital, with informed consent provided electronically by participants.ResultsThe survey indicated that all physicians encountered suspected or confirmed cases of sJIA, highlighting its prevalence and the diagnostic challenges associated. Regarding diagnostic standards, 53.9% of physicians used the “Consensus on the Diagnosis and Treatment of sJIA and Macrophage Activation Syndrome,” 18.1% followed the International League of Associations for Rheumatology (ILAR) standards, and 24.8% adhered to the Pediatric Rheumatology International Trials Organization (PRINTO) standards. In treatment strategies, glucocorticoids and IL-6 receptor monoclonal antibodies were extensively used, with the latter receiving “excellent” and “satisfactory” ratings of 46.5% and 36.1%, respectively, demonstrating high efficacy and acceptance. Main challenges included high treatment costs, complexity of diagnosis, patient compliance issues, and potential long-term side effects of biologics. Additionally, 126 doctors (40.7%) actively participated in more than three academic conferences or systematic learning courses related to sJIA, indicating a strong demand for ongoing education, particularly in new treatment developments and diagnostic skills.ConclusionThe findings emphasize the necessity for standardized diagnosis and customized treatment plans tailored to patient-specific conditions in managing sJIA.Key Points• The survey highlights the prevalence and clinical challenges of sJIA among physicians, emphasizing the importance of vigilant diagnosis, multi-system involvement, and differential diagnosis to improve treatment outcomes and patient quality of life.

Electrografted Laser-Induced Graphene: Direct Detection of Neurodegenerative Disease Biomarker in Cerebrospinal Fluid.

There are more than 50 neurodegenerative disorders, and amyotrophic lateral sclerosis (ALS) is one of the most common disorders that poses diagnostic and treatment challenges. The poly glycine-proline (polyGP) dipeptide repeat is a toxic protein that has been recognized as a pharmacodynamic biomarker of C9orf72-associated (c9+) ALS, a subtype of ALS that originates from genetic mutation. Early detection of polyGP will help healthcare providers start timely gene therapy. Herein, we developed a label-free electrochemical immunoassay for the simple detection of polyGP in unprocessed cerebrospinal fluid (CSF) samples collected from ALS patients in the National ALS Biorepository. For the first time, an electrografted laser-induced graphene (E-LIG) electrode system was employed in a sandwich format to detect polyGP using a label-free electrochemical impedance technique. The results show that the E-LIG-modified surface exhibited high sensitivity and selectivity in buffer and CSF media with limit of detection values of 0.19 and 0.27 ng/mL, respectively. The precision of the calibration model was better in CSF than in the buffer. The E-LIG immunosensor can easily select polyGP targets in the presence of other dipeptide proteins translated from the c9 gene. Further study with CSF samples from ALS patients demonstrated that the label-free E-LIG-based immunosensor not only quantified polyGP in the complex CSF matrix but also distinguished between c9+ and non-c9- ALS patients.

Mycobacteriophages and Their Applications.

Mycobacterial infections caused by tuberculous and non-tuberculous strains pose significant treatment challenges, especially among immunocompromised patients. Conventional antibiotic therapies often fail due to bacterial resistance, highlighting the need for alternative therapeutic strategies. Mycobacteriophages are emerging as promising candidates for the treatment of mycobacteria. This review comprehensively explores phage isolation, characterization, and clinical applications. Despite the need for more extensive in vitro and in vivo studies, existing evidence shows their efficacy against both sensitive and antibiotic-resistant mycobacterial strains, even under disease-mimicking conditions, particularly when used in cocktails to minimize resistance development. Mycobacteriophages can be engineered and evolved to overcome limitations associated with lysogeny and narrow host range. Furthermore, they exhibit activity in ex vivo and in vivo infection models, successfully targeting mycobacteria residing within macrophages. Delivery methods such as bacterial and liposomal vectors facilitate their entry into human cells. Considering the potential for phage-treatment-induced bacterial resistance, as described in this review, the combination of mycobacteriophages with antibiotics shows efficacy in countering mycobacterial growth, both in the laboratory setting and in animal models. Interestingly, phage-encoded products can potentiate the activity of relevant antibiotics. Finally, the application of phages in different compassionate cases is reported. The positive outcomes indicate that phage therapy represents a promising solution for the treatment of antibiotic-resistant mycobacteria.

Dose escalation in radical radio(chemo)therapy for cervical and upper thoracic esophageal cancer with 3DCRT/IMRT (ChC&UES): a multicenter retrospective study

BackgroundCervical and upper thoracic esophageal cancer (ESCA) presents treatment challenges due to limited clinical evidence. This multi-center study (ChC&UES) explores radical radio(chemo)therapy efficacy and safety, especially focusing on radiation dose.MethodWe retrospectively analyzed clinical data from 1,422 cases across 8 medical centers. According to the radiation dose for primary gross tumor, patients were divided into standard dose radiotherapy (SD, 50–55 Gy) or high dose (HD, > 55 Gy) radiotherapy. HD was further subdivided into conventional- high-dose group (HD-conventional, 55–63 Gy) and ultra-high-dose group (HD-ultra, ≥ 63 Gy). Primary outcome was Overall Survival (OS).ResultsThe median OS was 33.0 months (95% CI: 29.401–36.521) in the whole cohort. Compared with SD, HD shown significant improved survival in cervical ESCA in Kaplan-Meier (P = 0.029) and cox multivariate regression analysis (P = 0.024) while shown comparable survival in upper thoracic ESCA (P = 0.735). No significant difference existed between HD-conventional and HD-ultra in cervical (P = 0.976) and upper thoracic (P = 0.610) ESCA. Incidences of radiation esophagitis and pneumonia from HD were comparable to SD (P = 0.097, 0.240), while myosuppression risk was higher(P = 0.039). The Bonferroni method revealed that, for both cervical and upper thoracic ESCA, HD-ultra enhance the objective response rate (ORR) compared to SD (P < 0.05).ConclusionHD radiotherapy benefits cervical but not upper thoracic ESCA, while increasing bone marrow suppression risk. Further dose escalating (≥ 63 Gy) doesn’t improve survival but enhances ORR.

Application effect of case management nursing based on patient safety in patients with prostate cancer.

Globally, prostate cancer has become a major threat to men's health, with an increasing incidence and causes serious effects on the quality and length of life of patients. Despite the rapid development of medical technology, which provides treatments, including surgery, radiotherapy, and endocrine therapy, the treatment of patients with prostate cancer, especially with endocrine therapy, has become a major challenge in clinical treatment owing to the lengthy course of treatment, side effects of drugs, and impact of the disease on the psychological and physiological functioning of the patient, producing poor treatment adherence and a decline in quality of life. To explore effects of nursing intervention prioritizing patient safety and case management in patients with prostate cancer undergoing endocrine therapy. Eighty patients with prostate cancer who received endocrine therapy at our hospital between January 2022 and January 2024 were divided into observation and control groups with 40 cases per group. The control group was treated using a routine nursing workflow while the observation group received case management nursing guidance prioritizing patient safety. Scores for anxiety and depression, prostate cancer symptoms, and quality of life and patient compliance and satisfaction were compared between the groups after three months of intervention. After the nursing intervention, the anxiety and depression scores of the observation group were significantly lower than those of the control group (P < 0.05). The quality of life score, sexual function, and hormone function were significantly higher than those in the control group (P < 0.05). Case management guidance based on patient safety effectively reduced anxiety and depression in patients undergoing endocrine therapy for prostate cancer and improved their quality of life, treatment compliance, and satisfaction.

Revolutionizing CAR T-Cell Therapies: Innovations in Genetic Engineering and Manufacturing to Enhance Efficacy and Accessibility.

Chimeric antigen receptor (CAR) T-cell therapy has achieved notable success in treating hematological cancers but faces significant challenges in solid-tumor treatment and overall efficacy. Key limitations include T-cell exhaustion, tumor relapse, immunosuppressive tumor microenvironments (TME), immunogenicity, and antigen heterogeneity. To address these issues, various genetic engineering strategies have been proposed. Approaches such as overexpression of transcription factors or metabolic armoring and dynamic CAR regulation are being explored to improve CAR T-cell function and safety. Other efforts to improve CAR T-cell efficacy in solid tumors include targeting novel antigens or developing alternative strategies to address antigen diversity. Despite the promising preclinical results of these solutions, challenges remain in translating CAR T-cell therapies to the clinic to enable economically viable access to these transformative medicines. The efficiency and scalability of autologous CAR T-cell therapy production are hindered by traditional, manual processes which are costly, time-consuming, and prone to variability and contamination. These high-cost, time-intensive processes have complex quality-control requirements. Recent advancements suggest that smaller, decentralized solutions such as microbioreactors and automated point-of-care systems could improve production efficiency, reduce costs, and shorten manufacturing timelines, especially when coupled with innovative manufacturing methods such as transposons and lipid nanoparticles. Future advancements may include harmonized consumables and AI-enabled technologies, which promise to streamline manufacturing, reduce costs, and enhance production quality.