Efficacy Of Therapy Research Articles

Endoscopic management of upper non-variceal and lower gastrointestinal bleeding: Where do we stand?

Non-variceal upper gastrointestinal bleeding (GIB) remains a significant clinical challenge with a 30-day mortality of up to 11%. Peptic ulcers are the most common cause, followed by other conditions like Mallory-Weiss syndrome, Dieulafoy’s lesions, and gastric neoplasms. Treatment strategies include acid-suppressive therapy, endoscopic interventions, and surgical or radiological procedures. Endoscopic techniques such as over-the-scope clips, coagulation graspers, and endoscopic ultrasound-guided treatments have significantly improved outcomes, reducing rebleeding rates and the need for surgery. Injectable therapies, mechanical hemostasis via clips, and thermal modalities (e.g. , electrocoagulation, argon plasma coagulation) remain standard approaches for active bleeding. Newer hemostatic powders, such as TC-325, offer promising non-contact treatments, particularly in cases of refractory bleeding or malignancy. Doppler endoscopic probes aid in risk stratification by detecting residual arterial blood flow, improving the efficacy of endoscopic therapy and reducing rebleeding risks. For small bowel bleeding, endoscopic management with enteroscopy and thermal therapies remains key, though medical therapies are evolving. Lower GIB, which often involves conditions like diverticular disease and angioectasia, requires a comprehensive approach combining endoscopic, radiologic, and surgical interventions. Pharmacologic management focuses on balancing antithrombotic therapy with bleeding risks, with reversal agents playing a crucial role in life-threatening bleeding episodes. This review highlights advances in diagnostic tools and endoscopic therapies that have enhanced management outcomes for GIB across various etiologies.

Efficacy of Prolotherapy for Temporomandibular Joint Dysfunction: An Interventional Clinical Study.

BACKGROUND This research is aimed at minimizing the patient's discomfort and suffering from temporomandibular joint disorders through less-invasive procedures to evaluate the efficacy of proliferative injection therapy, particularly prolotherapy, in fearful patients with temporomandibular joint (TMJ) disorders. MATERIAL AND METHODS A structured questionnaire covering symptom intensity and presence or absence of TMJ clicking and joint hypermobility in patients with confirmed temporomandibular disorder symptoms was completed by patients. Mouth opening and maximum incisor height was measured in millimeters. Degree of pain was obtained from the Visual Analog Scale score. The patients were referred to an oral surgeon who did the prolotherapy procedure, and this was repeated at the end of 1, 3, and 6 months. The collected data were analyzed using the Chi-square and t-tests. RESULTS The patients' pain decreased from the third month of treatment until the end of the sixth month of the treatment program, and patient mouth opening ability was significantly different (F=3. 56; df=2; P<0. 05). After a duration of 3 months of the process of treatment, crepitus and periauricular discomfort were reduced. In terms of pain and mouth opening, prolotherapy in treating temporomandibular disorder was generally beneficial as shown by the P<0.05 scores. CONCLUSIONS From this evaluation, prolotherapy using 50% dextrose as a single injection via a conventional protocol, which can be single dosage or several doses, is recommended as treatment for chronic recurring dislocations and mandibular subluxations. Recurrent or severe cases can only be managed through operations. Much larger studies with greater sample sizes and even longer follow-up periods are necessary for the results of this study to be supported.

Blood-based biomarkers in soft tissue sarcoma: Implications for immune checkpoint inhibitor therapy.

Soft tissue sarcoma (STS) is a rare and heterogeneous cancer, comprising approximately 1% of all adult cancers and 7%-15% of all childhood cancers. In the advanced stages, chemotherapy remains the standard-of-care, but efficacy is limited, with a response rate of 15%-30%, and responses are often short-lived, with median progression-free survival typically of 6 months. Moreover, patients with advanced or metastatic STS have a median overall survival of only 18-24 months. Immune checkpoint inhibitors (ICI) have revolutionized the treatment of various cancers including melanoma and non-small cell lung cancer (NSCLC). Emerging evidence from recent clinical trials indicates that certain STS subtypes may be amenable to immunotherapy. A critical challenge, however, is identifying biomarkers that can accurately predict and enable monitoring of ICI responses, to enable better patient selection and to improve outcomes. This narrative review highlights the current research gap in the treatment of STS patients with ICI therapy, particularly the absence of reliable blood-based biomarkers to predict ICI response. In this review, we examine current clinical trials investigating the efficacy of ICI therapy in patients with STS and summarise circulating immune-related prognostic biomarkers in STS, including haematological indices, peripheral blood mononuclear cells, circulating proteins and DNA, and evaluate their potential as predictive biomarkers for ICI therapy. We propose that these immune-associated molecules may serve as predictive biomarkers to differentiate and monitor ICI response, thus presenting opportunities for personalised treatment for patients with STS.

Evaluation of the efficacy of sulbactam combination therapy for monomicrobial and polymicrobial pulmonary infections caused by multidrug-resistant Acinetobacter baumannii.

The efficacy in treatment of monomicrobial versus polymicrobial Acinetobacter baumannii (mono-AB vs poly-AB) pulmonary infections remains unclear. This study mainly investigated the efficacy of sulbactam combination regimens against mono-AB and poly-AB pulmonary infections. A multicenter retrospective study of adult patients who received sulbactam or cefoperazone/sulbactam for multidrug-resistant A. baumannii (MDRAB) between August 2021 and July 2023 was conducted. The outcomes of 7-day microbiological efficacy and 14-day clinical efficacy were measured. A total of 366 patients were enrolled, including 75 mono-AB patients. Among the 291 poly-AB cases, 82 patients were co-infected with Pseudomonas aeruginosa and 76 patients with Klebsiella pneumoniae. All A. baumannii isolates exhibited multidrug resistance. The antibiotics demonstrating the highest sensitivity against these isolates were polymyxins and tigecycline, with sensitivity rates of 91.25% and 71.63%, respectively. In the multivariable analysis, patients receiving sulbactam-based treatment for poly-AB pulmonary infections exhibited significantly higher microbial clearance of A. baumannii compared with those with mono-AB infections. Microbial efficacy analysis of A. baumannii co-infection with K. pneumoniae or P. aeruginosa showed similar results to overall poly-AB infections. Sulbactam doses ≥ 8 g/day showed the best microbiological and clinical efficacy. Sulbactam combined with tigecycline and/or polymyxins demonstrated significantly better microbiological efficacy compared with sulbactam alone. Sulbactam combined with polymyxins resulted in better microbiological and clinical efficacy than when combined with tigecycline. In conclusion, patients with poly-AB lung infections exhibit a higher microbial clearance rate of A. baumannii following treatment compared with those with mono-AB infections. A daily dose ≥8 g sulbactam may be optimal for treating MDRAB pneumonia. The combination of sulbactam and polymyxins demonstrates significant advantages over other sulbactam-containing regimens in terms of microbiological and clinical efficacy.IMPORTANCEThis is the first multicenter retrospective study to investigate the efficacy of sulbactam combination regimens in the treatment of monomicrobial and polymicrobial AB-related pulmonary infections. Our study found that patients receiving sulbactam-based treatment for poly-AB pulmonary infections exhibited significantly higher microbial clearance of A. baumannii compared with those with mono-AB infections. Microbial efficacy analysis of A. baumannii co-infection with K. pneumoniae or P. aeruginosa showed similar results to overall poly-AB infections. These findings are significantly important for further analyzing the potential mechanisms underlying the differences in efficacy between antimicrobial treatments for monomicrobial and polymicrobial infections, as well as for optimizing clinical antimicrobial combination strategies.

Preconditioning of bone marrow mesenchymal stem cells with sodium hydrosulfide enhances their therapeutic potential in type II collagen-induced arthritis rat model.

This study was conducted to evaluate the impact of sodium hydrogen sulfide (NaHS) on the therapeutic efficacy of bone marrow mesenchymal stem cells (BM-MSCs) in the treatment of collagen-induced arthritis (CIA) rats.MSCs were isolated and cultured from rat bone marrow, and their characteristics were determined. The CIA model was induced in rats by intradermal injections of type II collagen on days 0 and 21. A variety of treatments were administered, including naproxen, BM-MSCs, BM-MSC-conditioned media, NaHS, BM-MSCs preconditioned with NaHS, and BM-MSCs preconditioned with NaHS-conditioned media.The infused BM-MSCs homed to the bone trabeculae and cartilage of the knee joint, leading to significant improvements in gait scores and a reduction in paw withdrawal frequency (PWF). Treatment with BM-MSCs and NaHS also significantly suppressed serum levels of CRP, RF, and 14-3-3η, while downregulating TNF-α gene expression and MMP-1 protein levels in the synovial membrane. Histopathological analysis confirmed these biochemical and molecular genetic findings.Notably, CIA rats treated with BM-MSCs preconditioned with NaHS showed the most significant improvements, with outcomes closely resembling those of healthy controls. This study concludes that NaHS enhances the therapeutic efficacy of BM-MSC therapy for rheumatoid arthritis (RA) by augmenting their anti-inflammatory, immunomodulatory, and regenerative properties.

Retrospective Clinical and Radiological Comparison of Intradiscal Ozone and Ozone + PRP Therapy Results in Patients with Intervertebral Disc Degeneration.

This retrospective study aimed to evaluate and compare the clinical efficacy of intradiscal ozone therapy (OT) against a combination therapy of ozone and platelet-rich plasma (PRP) in patients diagnosed with intervertebral disc degeneration (IVDD). The study included a cohort of 50 patients, divided equally into two groups of 25, who received either intradiscal OT or ozone + PRP combination therapy between February 2022 and February 2023. The sample comprised 20 females and 30 males, with ages ranging from 19 to 76 years (mean age 48.8). Pain intensity was measured using the visual analog scale (VAS), while disability levels were assessed using the oswestry disability index (ODI) prior to treatment and at 1, 3, and 6 months post-treatment. Additionally, lumbar magnetic resonance imaging was conducted at the 3-month mark post-treatment, with evaluations based on the Pfirrmann disc degeneration classification. Significant improvement in both VAS and ODI scores was observed in both treatment groups (P < 0.001). The ozone + PRP combination therapy group exhibited no statistically significant difference in VAS and ODI scores compared to the ozone-only group (P > 0.05). Intradiscal OT and the ozone + PRP combination therapy represent effective minimally invasive treatment options for patients suffering from IVDD, yielding substantial clinical benefits with minimal side effects. That is why it is suggested as a potential preferred therapeutic approach prior to the consideration of surgical interventions.

Phage therapy: a promising approach for Staphylococcus aureus diabetic foot infections.

Diabetic foot infections (DFIs), predominantly caused by Staphylococcus aureus, pose a significant healthcare challenge with severe consequences, including amputation. Phage therapy, which utilizes bacteriophages to specifically target bacterial pathogens, has emerged as a promising alternative to conventional antibiotic treatments. This review evaluates the efficacy of phage therapy as a complementary treatment for DFIs caused by S. aureus, synthesizing evidence from preclinical and clinical studies while addressing the limitations and challenges associated with current research. The analysis highlights promising results from diabetic animal models, demonstrating effective bacterial load reduction and improved wound healing. Clinical case reports and series further underline significant improvements in infection management and ulcer healing, with no major adverse effects reported. Ongoing clinical trials are also discussed, offering insights into the study parameters evaluating phage therapy potential efficacy and safety for S. aureus-related DFIs. While the collected data highlight the potential of phage therapy as a valuable complement to traditional antibiotic treatments, particularly in managing antibiotic-resistant infections, further research is essential to address existing limitations, including gaps in long-term efficacy data and challenges in standardization. With continued investigation, phage therapy holds significant potential to alleviate the healthcare burden of DFIs and improve patient outcomes.

Smart Type I Squaraine Nano-Photosensitizer Combined with MnO2 for Tumor-Targeted and Ferroptosis-Induced Immunogenic Photodynamic Therapy.

Most photosensitizers face enormous challenges in tumor hypoxia, the redox microenvironment, and low immune efficacies for reactive oxygen species (ROS). Herein, dye SQ-580 was constructed by coupling the electron-donating indole and thiophenazine-thiophene with the electron-withdrawing dicyanovinyl squaraine. It exhibited a high generation of •OH and O2•- by decreasing ΔES1T2 and acted as an excellent type I photosensitizer for conquering tumor hypoxia. The nanoplatform involving SQ-580, MnO2, and a targeting peptide CREKA was constructed and targeted breast tumor. In the tumor microenvironment, MnO2 reacted with high-expressed GSH and produced Mn2+, which catalyzed H2O2 to decompose into •OH and induced chemodynamic therapy (CDT). The reduction of GSH inhibited the consumption of SQ-580 and maintained its high photodynamic therapy (PDT) efficacy. GSH depletion and ROS resulted in cell ferroptosis. Under the synergy of ferroptosis and ROS, Mn2+ amplified immunogenic cell death (ICD). In the mouse models, SQ-580@MnO2 NPs showed NIRF/MR imaging-guided tumor targeting, effectively inhibited the growth of the primary and distant tumors, and amplified PDT and immune efficacies in the synergy of PDT, CDT, ferroptosis, and ICD. This study provides an effective strategy to design excellent type I photosensitizers and amplify the PDT and ICD efficacies utilizing valence metals and the tumor microenvironment.

Effectiveness and Safety of Immune Checkpoint Inhibitors in Colorectal Cancer: A Systematic Review of Real-World Studies.

Immune checkpoint inhibitors (ICIs) have demonstrated significant efficacy in the treatment of colorectal cancer (CRC). However, most evidence has come from clinical trials with strict eligibility criteria. Understanding real-world effectiveness and safety of ICIs in CRC is important to guide routine clinical practice across diverse populations. A systematic review following PRISMA guidelines was conducted to identify observational studies evaluating ICI-based regimens compared to conventional or combination therapies in patients with CRC. Three databases (MEDLINE, Embase, and Scopus) were searched from inception through March 15, 2025. Eligible studies reported at least one efficacy outcome (e.g., progression-free survival [PFS], overall survival [OS], etc.) and/or safety outcome (e.g., adverse events) among real-world populations with CRC treated with ICIs. Study quality was assessed using the Newcastle-Ottawa Scale, and a narrative synthesis was performed to summarize the key findings. Eleven real-world studies met the inclusion criteria, encompassing data from 2,049 patients. In MSI-H/dMMR metastatic CRC, real-world findings aligned with the survival benefits observed in clinical trials, demonstrating improved PFS and OS compared to conventional therapies. For MSS/pMMR metastatic CRC, combining ICIs with other agents (e.g., tyrosine kinase inhibitors or chemotherapy) showed improvements but yielded conflicting results. Overall, the safety profiles were comparable to conventional therapies, with treatment-related adverse events occurring at similar rates. Real-world evidence supports the efficacy of ICI monotherapy in MSI-H/dMMR metastatic CRC and suggests potential benefits of ICI-based combination therapies in MSS/pMMR metastatic CRC. However, most of the data are derived from small, single-center cohorts, which limit their generalizability. Further multi-center studies are needed, especially to assess the efficacy of ICI-based combination therapies in the broader CRC population.

Revisiting the Open Vein Hypothesis to Reduce the Postthrombotic Syndrome: Implications for Multidisciplinary Care and Research: A Scientific Statement From the American Heart Association.

The "open vein hypothesis" postulates that early thrombus clearance and restoration of venous blood flow may prevent postthrombotic syndrome after proximal deep vein thrombosis. Since its proposal several decades ago, new insights from basic and clinical studies have motivated a re-evaluation and refinement of this hypothesis. According to data from these studies, susceptibility to postthrombotic syndrome occurs as a result of differences in genetic composition, thrombophilic conditions, predilection to inflammation and fibrosis, endogenous fibrinolytic capability, timing of s ymptom presentation and treatment initiation, and efficacy of antithrombotic therapy. Although initial restoration of an open vein appears to be beneficial for selected patient groups, freedom from postthrombotic syndrome is more likely in the setting of long-term venous patency, reduced recurrent thrombotic episodes, and reduced perithrombotic (eg, vein wall and valve) inflammation. These underlying biological mechanisms need further elucidation, with a long-term goal of personalizing treatment by mapping the individuals' clinical presentation with their underlying risk factors and assessing time-dependent biological processes that occur as a clinical venous thrombosis resolves. This scientific statement (1) highlights historical fundamentals of the open vein hypothesis and then showcases new research insights into the pathophysiological factors driving postthrombotic syndrome; (2) discusses advantages and disadvantages of imaging modalities for deep vein thrombosis used in clinical practice, including the potential to depict thrombus chronicity and status of vein wall injury; (3) proposes measures to develop integrated multidisciplinary care for deep vein thrombosis focused on the reduction of postthrombotic syndrome; and (4) identifies priority areas and questions for further research.

Comparison of the efficacy of peloid therapy and paraffin treatment in carpal tunnel syndrome.

Carpal tunnel syndrome (CTS) is a common neuropathy caused by median nerve compression at the wrist, managed with treatments like splinting, physical therapy, injections, and surgery. This study aimed to compare the effectiveness of paraffin and peloid therapies combined with night splint use in reducing symptom severity, improving functional status, and enhancing electrophysiological findings in patients with mild to moderate CTS.Sixty patients with mild to moderate CTS scheduled for paraffin or peloid therapy with night splint use were included. Symptom severity was assessed using the Visual Analog Scale (VAS) and the Boston Carpal Tunnel Syndrome Questionnaire's Symptom Severity Scale (BSSS). Functional status was evaluated with the Functional Status Scale (BFSS). Electrophysiological parameters, including distal sensory latency (DSL), distal motor latency (DML), sensory nerve action potential (SNAP), compound muscle action potential (CMAP), sensory conduction velocity (SCV), and motor conduction velocity (MCV), were measured via electromyography (EMG). Assessments were performed at baseline, and at the 4th and 12th weeks post-treatment. Both therapies significantly improved VAS and BSSS scores at the 4th and 12th weeks (p < 0.05). Functional status improved only in the paraffin group (p < 0.05). Electrophysiological improvements in DSL and DML were significant in the paraffin group (p < 0.05), while no significant changes were noted in the peloid group. Between-group comparisons showed significant differences in DSL, DML, and SCV in favor of paraffin (p < 0.05). Paraffin and peloid therapies with night splint use reduce CTS symptom severity, but paraffin is superior in improving function and nerve conduction.

Comparative Efficacy of Non-Statin Lipid-Lowering Therapies in Patients With Hypercholesterolemia at Increased Cardiovascular Risk: An Updated Network Meta-Analysis.

Hypercholesterolemia is associated with atherosclerotic cardiovascular disease (ASCVD), a leading cause of morbidity and mortality. Non-statin lipid-lowering therapies (LLTs) such as ezetimibe, proprotein convertase subtilisin/kexin type 9 (PCSK9) monoclonal antibodies (mAbs), bempedoic acid, and inclisiran have been recommended in clinical guidelines to treat patients with ASCVD and/or high cardiovascular (CV) risk having elevated low-density lipoprotein cholesterol (LDL-C) despite being treated with maximally tolerated doses (MTD) of statins. Our previously published network meta-analysis (NMA)1 was updated in this study to evaluate comparative efficacy of non-statin LLTs in reducing LDL-C among patients with ASCVD and/or high CV risk receiving MTD statins. The systematic literature review previously conducted to inform our NMA was updated through January 2023, wherein more recent clinical trials of non-statin LLTs (ORION-15, ORION-18, HUA TUO) and additional data on monthly dosing regimens for PCSK9 mAbs were included. The outcome of interest was percentage change in LDL-C at week 24. Random-effects Bayesian NMA was performed. Comparative efficacy was estimated as mean difference (MD) with 95% credible interval (CrI). A total of 20 trials were deemed relevant for the NMA. Consistent with the previous findings from our NMA, this study demonstrated that inclisiran provided superior efficacy in LDL-C lowering compared with ezetimibe and bempedoic acid (MD: -44.24 [95% CrI: -51.84, -36.70]). This NMA further reaffirmed that inclisiran provided comparable LDL-C reduction vs. alirocumab (MD: -1.93% [95% CrI: -8.56, 4.20]) and evolocumab (MD: 2.00% [95% CrI: -4.58, 8.60]) among patients with ASCVD and/or high CV risk on MTD statins.

Targeting Cell Signalling Pathways with New Small Molecules in Inflammation and Cancer.

In the treatment of cancer and inflammation, small molecules become powerful therapeutic tools that provide new therapeutic approaches with improved efficacy and fewer side effects. This review offers a thorough summary of current developments in small-molecule drugs that target cancer and inflammatory pathways. Specifically, inhibition of phosphodiesterase-4 (PDE4) and COX receptors have demonstrated potential in the field of inflammation to help mitigate a variety of inflammatory disorders. We examine the structural design, mechanism of action, and therapeutic potential of innovative small compounds that inhibit or alter these pathways. Significant attention is placed on the dual anti-inflammatory and anti-cancer properties of these substances. The evaluation emphasizes preclinical and clinical data, revealing the most promising candidates under development. In summary, the precise manipulation of cellular signalling pathways by small compounds constitutes a dynamic domain with the capacity to revolutionize therapeutic approaches for inflammation and cancer. Ongoing investigation of these chemicals is essential for the advancement of safer and more efficacious therapies.

Janus Kinase Inhibitors in the Treatment of Crohn’s Disease and Ulcerative Colitis: A Review

Introduction and purpose: Insufficient efficacy and adverse effects of classical therapies for inflammatory bowel disease (IBD), such as ulcerative colitis and Crohn's disease, have prompted the search for new, more targeted treatment methods. Janus kinase (JAK) inhibitors are a new group of oral drugs that modulate the proinflammatory cytokine signaling pathway. The aim of this review is to present the state of knowledge on the efficacy and safety of currently registered JAK inhibitors in the treatment of IBD. Review Methods: A systematic search of the PubMed database was conducted, focusing on publications from the last five years as well as selected key earlier studies. The search strategy included relevant keywords related to Janus kinase (JAK) inhibitors and inflammatory bowel disease (IBD). The most pertinent articles aligned with the study objective were reviewed and included. State of knowledge: JAK inhibitors, such as tofacitinib, upadacitinib, and filgotinib, have shown high efficacy in the treatment of moderate to severe UC and CD, especially in patients with insufficient biological therapy response. Clinical studies confirm their efficacy in inducing and maintaining remission and improving endoscopic findings. The most common adverse events are infections (including herpes zoster), and elevation of creatine kinase and lipids. The safety profile remains acceptable, although it requires monitoring, especially at higher doses, and further investigation. Summary: JAK inhibitors are an effective and promising therapeutic option for IBD, offering a rapid onset of action and good symptom control. Despite the favorable clinical effects, an individual approach to treatment and monitoring for adverse effects are necessary, especially with long-term use.

Serum lipid metabolites predict the efficacy of intravenous immune globulin therapy in patients with pediatric dilated cardiomyopathy

The response of pediatric dilated cardiomyopathy (PDCM) patients to intravenous immune globulin (IVIG) varies from cardiac functional recovery to heart transplantation and even death. IVIG therapy can significantly improve the left ventricular ejection fraction (LVEF) in some PDCM patients, but indicators for evaluating the response to IVIG therapy are lacking. Lipid metabolic disturbance is associated with changes in cardiac function, but no studies have examined the associations between lipidomics markers and the efficacy of IVIG. Discovery analyses were based on 322 targeted lipids in a retrospective cohort study. T tests, orthogonal‒orthogonal projections to latent structures discriminant analysis (OPLS-DA) and random forest (RF) analysis were used to screen the candidate lipids. Associations of the candidate lipids were examined via Cox proportional hazards regression models. We subsequently developed a score for the candidate lipid metabolites, which was then used to classify children into two groups (0–3 and 4), and the survival curves of the two groups were drawn. There were 31 patients in the discovery set and 24 patients in the validation set. Adverse events which were defined as death, heart transplant, and rehospitalization for HF were observed in 23 patients (41.8%). After adjusting for age, LVEF, and the LV end-diastolic diameter z score, CE-16:1, PE36:4p, PE40:6p, and PE40:6p (22:6) were significantly associated with the occurrence of adverse events in the discovery set. The results were also consistent in the validation set, and the hazard ratios (HRs) were 2.638 (95% CI 1.042–6.683; p = 0.041), 0.549 (95% CI 0.340–0.886; p = 0.014), 0.271 (95% CI 0.109–0.672; p = 0.005), and 0.299 (95% CI 0.121–0.741; p = 0.009), respectively. We developed a score for these four lipid metabolites. When the score reached 4, adverse events were more likely to be observed in both sets. Serum lipid metabolites can be used to predict the efficacy of IVIG in children with DCM.

Sitravatinib targets TYRO3 to augment the anti-tumor immune response of PD-1 blockade in hepatocellular carcinoma.

Tyrosine kinase inhibitors (TKIs) combined with immune checkpoint blockades (ICBs) produce enhanced anti-tumor activity in the treatment of advanced hepatocellular carcinoma (HCC). Sitravatinib is a novel multi-target TKI that targets TYRO3, AXL, MERTK (TAM) receptors, c-MET, etc. This study aimed to investigate the anti-tumor efficacy and immunomodulatory activity of sitravatinib in HCC. Human HCC cell lines and xenograft models were used to explore the anti-tumor activity of sitravatinib. Subcutaneous and orthotopic immunocompetent murine HCC models were used to assess the therapeutic efficacy of sitravatinib and PD-1 blockade combination therapy. Co-cultures for tumor cells and T cells were performed to verify the immunomodulatory effect of sitravatinib in tumors. Sitravatinib showed potent anti-tumor activity and immunomodulatory capabilities from in vitro to in vivo. Sitravatinib treatment synergized with PD-1 blockade to generate an increased anti-tumor efficacy, leading to significant enrichment of cytotoxic CD8+ T cells as well as reduction of Treg cells infiltration in tumors. Mechanically, on one hand, sitravatinib reinforced MHC-I expression by blocking TYRO3-STAT1 axis, thereby sensitizing tumor cells to T cell liking. On the other hand, sitravatinib suppressed tumor-secreted IL33 by inhibiting TYRO3 activity in HCC cells, resulting in reduced Treg cells differentiation and consequently liberating CD8+ T cell cytotoxic capacity. In the clinic, one advanced HCC patient treated with Sitravatinib plus PD-1 blockade achieved near complete response and remains disease progression-free for more than two years. Collectively, we demonstrated a rationale for combining sitravatinib with PD-1 blockade in the treatment for HCC.

Advancements in Complement Inhibition for PNH and Primary Complement Mediated Thrombotic Microangiopathy.

Paroxysmal nocturnal hemoglobinuria (PNH) and primary complement-mediated thrombotic microangiopathy (CM-TMA), also known as atypical hemolytic uremic syndrome (aHUS), are hematologic disorders characterized by dysregulation of the complement system leading to hemolysis and other systemic and potentially lethal complications. The advent of C5 inhibition with agents such as eculizumab and ravulizumab has revolutionized the management of patients with these disorders, though some may still experience clinically significant breakthrough extravascular hemolysis. Over the past several years, novel therapies targeting upstream pathways of complement inhibition have been approved for the treatment of patients with PNH experiencing breakthrough hemolysis despite C5 inhibition. These agents currently include pegcetacoplan, a C3 inhibitor, iptacopan, an oral factor B inhibitor, danicopan, an oral factor D inhibitor, and crovalimab, an anti-C5 monoclonal antibody. This review highlights recent advances in complement-targeted therapies for PNH, including their indications and efficacy and safety data from key randomized trials. In addition, we review current data supporting the use of these novel agents for aHUS, for which only the terminal complement inhibitors eculizumab and ravulizumab are currently approved. Future research is crucial to establish the long-term efficacy and safety profiles of these novel therapies, ensuring the best treatment strategies for patients with PNH and aHUS.

Innovative applications of silicon dioxide nanoparticles for targeted liver cancer treatment

Liver cancer remains a major global health challenge, characterized by high mortality and limited treatment efficacy. Conventional therapies, including chemotherapy, immunotherapy, and viral vectors, are hindered by systemic toxicity, drug resistance, and high costs. Silica nanoparticles (SiO2NPs) have emerged as promising platforms for liver cancer therapy, offering precise drug delivery, stimuli-responsive release, and integrated diagnostic-therapeutic capabilities. This review critically examines the potential of SiO2NPs to overcome these therapeutic limitations. Notable advances include their high drug-loading capacity, customizable surface modifications, and dual-responsive systems (pH/redox/NIR-II) that enable &amp;gt;90% tumor-specific drug release. Preclinical studies have demonstrated synergistic efficacy in combination therapies. Additionally, theranostic SiO2NPs enable MRI-guided tumor delineation and real-time treatment monitoring. Despite promising results, challenges remain in long-term biosafety, scalable synthesis, and regulatory compliance. Early-phase clinical trials, including those using NIR-II-responsive platforms, highlight their translational potential but underscore the need for further validation of toxicity profiles and manufacturing standards. Future research should focus on optimizing combinatory treatment strategies, scaling up production, and aligning with evolving regulatory frameworks. By bridging nanomaterial innovation with clinical applications, SiO2NPs offer unparalleled potential for advancing precision oncology in hepatocellular carcinoma.

Efficacy and safety of dual-targeted therapy for refractory inflammatory bowel disease: a retrospective case series from three tertiary general hospitals in China

AimDual-targeted therapy (DTT) may offer a promising approach for treating refractory inflammatory bowel disease (IBD). The aim of this case series was to evaluate the safety and clinical response of DTT in clinical practice.MethodsWe retrospectively analyzed data from refractory inflammatory bowel disease (IBD) patients receiving dual-target therapy (DTT) across several Chinese IBD centers. The treatment combinations included biologic agents (infliximab (IFX), adalimumab (ADA), vedolizumab (VDZ), and ustekinumab (UST) and oral small molecule tofacitinib (TOF). We collected baseline characteristics, clinical and endoscopic activity indices, inflammatory markers (C-reactive protein and albumin), and adverse events to evaluate the clinical effectiveness, endoscopic response, biochemical remission, and safety profile of DTT.ResultsA total of 8 patients with ulcerative colitis (UC) and 10 with Crohn’s disease (CD) underwent DTT at three tertiary hospitals in China. All corticosteroids initiated at baseline (six cases) were completely discontinued within 3 months. Clinical response rates were 88.23% (15/17), 91.67% (11/12), and 100% (7/7) at 3, 6, and 9 months, respectively. Endoscopic response was achieved in 88.89% (8/9) of patients who were evaluated at 9 months. Adverse events included ustekinumab-associated arthralgia and alopecia in one UC patient and tofacitinib-related allergic purpura in another, both of which were subsequently transitioned to monotherapy. Two CD patients developed infections (Clostridium difficile and bacterial intestinal infection) at 3 months, were treated with oral antibiotics, and successfully continued their original DTT regimens.ConclusionOur findings suggest that dual-target therapy demonstrates promising efficacy and an acceptable safety profile in refractory IBD patients. DTT may represent a valuable therapeutic option for patients who have not responded to conventional monotherapies.

Comorbid sleep disorders among individuals with spinal cord injury.

To determine the rate of sleep-disordered breathing (SDB) in individuals with spinal cord injury (SCI). and its types (central and obstructive, and combined (COSA) and to assess the response to treatment using positive airway pressure (PAP) (defined as an apnea-hypopnea index (AHI) of less than 5 events per hour on initial PAP titration) in individuals with SCI. Individuals with SCI who underwent a full night of diagnostic polysomnography (PSG) from to 2010-2024 to determine the type of SDB and its severity using the AHI and central apnea index (CAI). The inclusion criteria were individuals with chronic SCI at low cervical or thoracic (at C4-T6 levels). who are not mechanically ventilated or had tracheostomies. "Central sleep apnea (CSA)" is diagnosed with an AHI of 5+ events/h and a CAI of at least 50% of the AHI. "Obstructive sleep apnea (OSA) only" is identified by an AHI of 5+ events/h and a CAI of less than 5 events/h. COSA is characterized by an AHI of 5+ events/h, with a CAI over 5 events/h but under 50% of the total AHI. The positive response to PAP therapy was based on the AHI level of less than 5 events/h after initiating PAP treatment and based on remote monitoring data. Among the 81 individuals who met the inclusion criteria, 12 patients (15%) were diagnosed with COSA, 4 patients (5%) presented with CSA only, 56 patients (69%) had OSA, and 8 patients (10%) exhibited no SDB. In a subset of participants (N=51) hypopneas were classified as obstructive or central events based on American Academy of Sleep Medicine (AASM) definition and revealed that approximately one-third (32%) had central or COSA, 63% had OSA, and 6% did not have SDB on PSG. A total of 35 (47%) individuals diagnosed with SDB underwent PAP titration and were prescribed PAP. Twenty (27%) individuals received PAP treatment, and only 17 (23%) continued their use for the initial three months. Only 11 patients (15%) demonstrated responsiveness to PAP on day 90 (AHI<5 during therapy). SDB is extremely common in individuals with SCI. The efficacy of PAP therapy is suboptimal, and adherence rates decline significantly over time.