Systemic oncological therapy in breast cancer patients on dialysis

The advancement of renal replacement therapy has significantly enhanced the survival rates of patients with end-stage renal disease(ESRD)over time.How-ever,this prolonged survival has also been associated with a higher likelihood of cancer diagnoses among these patients including breast cancer.Breast cancer treatment typically involves surgery,radiation,and systemic therapies,with ap-proaches tailored to cancer type,stage,and patient preferences.However,renal replacement therapy complicates systemic therapy due to altered drug clearance and the necessity for dialysis sessions.This review emphasizes the need for opti-mized dosing and administration strategies for systemic breast cancer treatments in dialysis patients,aiming to ensure both efficacy and safety.Additionally,ch-allenges in breast cancer screening and diagnosis in this population,including soft-tissue calcifications,are highlighted.

Molecular Therapy and Prevention of Liver Diseases

Molecular analyses have become an integral part of biomedical research as well as clinical medicine. The definition of the genetic basis of many human diseases has led to a better understanding of their pathogenesis and has in addition offered new perspectives for their diagnosis, therapy and prevention. Genetically, human diseases can be classified as hereditary monogenic, acquired monogenic and polygenic diseases. Based on this classification, gene therapy is based on six concepts: (1) gene repair, (2) gene substitution, (3) cell therapy, (4) block of gene expression or function, (5) DNA vaccination and (6) gene augmentation. While major advances have been made in all areas of gene therapy during the last years, various delivery, targeting and safety issues need to be addressed before these strategies will enter clinical practice. Nevertheless, gene therapy will eventually become part of the management of patients with various liver diseases, complementing or replacing existing therapeutic and preventive strategies.

Neural stem cell therapy for brain disease

Brain diseases, including brain tumors, neurodegenerative disorders, cerebrovasculardiseases, and traumatic brain injuries, are among the major disordersinfluencing human health, currently with no effective therapy. Due to the lowregeneration capacity of neurons, insufficient secretion of neurotrophic factors,and the aggravation of ischemia and hypoxia after nerve injury, irreversible lossof functional neurons and nerve tissue damage occurs. This damage is difficult torepair and regenerate the central nervous system after injury. Neural stem cells(NSCs) are pluripotent stem cells that only exist in the central nervous system.They have good self-renewal potential and ability to differentiate into neurons,astrocytes, and oligodendrocytes and improve the cellular microenvironment.NSC transplantation approaches have been made for various neurodegenerativedisorders based on their regenerative potential. This review summarizes anddiscusses the characteristics of NSCs, and the advantages and effects of NSCs inthe treatment of brain diseases and limitations of NSC transplantation that need tobe addressed for the treatment of brain diseases in the future.

Nutritional status and nutritional therapy in inflammatory bowel diseases

Underweight and specific nutrient deficiencies are frequent in adult patients with inflammatory bowel disease(IBD).In addition,a significant number of children with IBD,especially Crohn's disease(CD) have impaired linear growth.Nutrition has an important role in the management of IBD.In adults with CD,enteral nutrition(EN) is effective in inducing clinical remission of IBD,although it is less efficient than corticosteroids.Exclusive EN is an established primary therapy for pediatric CD.Limited data suggests that EN is as efficient as corticosteroids for induction of remission.Additional advantages of nutritional therapy are control of inflammation,mucosal healing,positive benefits to growth and overall nutritional status with minimal adverse effects.The available evidence suggests that supplementary EN may be effective also for maintenance of remission in CD.More studies are needed to confirm these findings.However,EN supplementation could be considered as an alternative or as an adjunct to maintenance drug therapy in CD.EN does not have a primary therapeutic role in ulcerative colitis.Specific compositions of enteral dietselemental diets or diets containing specific components-were not shown to have any advantage over standard polymeric diets and their place in the treatment of CD or UC need further evaluation.Recent theories suggest that diet may be implicated in the etiology of IBD,however there are no proven dietary approaches to reduce the risk of developing IBD.

Constraint-induced movement therapy promotes motor function recovery and downregulates phosphorylated extracellular regulated protein kinase expression in ischemic brain tissue of rats

Motor function impairment is a common outcome of stroke.Constraint-induced movement therapy（CIMT）involving intensive use of the impaired limb while restraining the unaffected limb is widely used to overcome the effects of＇learned non-use＇and improve limb function after stroke.However,the underlying mechanism of CIMT remains unclear.In the present study,rats were randomly divided into a middle cerebral artery occlusion（model）group,a CIMT＋model（CIMT）group,or a sham group.Restriction of the affected limb by plaster cast was performed in the CIMT and sham groups.Compared with the model group,CIMT significantly improved the forelimb functional performance in rats.By western blot assay,the expression of phosphorylated extracellular regulated protein kinase in the bilateral cortex and hippocampi of cerebral ischemic rats in the CIMT group was significantly lower than that in the model group,and was similar to sham group levels.These data suggest that functional recovery after CIMT may be related to decreased expression of phosphorylated extracellular regulated protein kinase in the bilateral cortex and hippocampi.

Applications and developments of gene therapy drug delivery systems for genetic diseases

Genetic diseases seriously threaten human health and have always been one of the refractory conditions facing humanity.Currently,gene therapy drugs such as siRNA,shRNA,antisense oligonucleotide,CRISPR/Cas9 system,plasmid DNA and miRNA have shown great potential in biomedical applications.To avoid the degradation of gene therapy drugs in the body and effectively deliver them to target tissues,cells and organelles,the development of excellent drug delivery vehicles is of utmost importance.Viral vectors are the most widely used delivery vehicles for gene therapy in vivo and in vitro due to their high transfection efficiency and stable transgene expression.With the development of nanotechnology,novel nanocarriers are gradually replacing viral vectors,emerging superior performance.This review mainly illuminates the current widely used gene therapy drugs,summarizes the viral vectors and non-viral vectors that deliver gene therapy drugs,and sums up the application of gene therapy to treat genetic diseases.Additionally,the challenges and opportunities of the field are discussed from the perspective of developing an effective nano-delivery system.

Is Goshinjo therapy effective in cognitive impairment after severe traumatic brain injury?

We report a case of a 21-year-old man who had severe traumatic brain injury as a result of an accident at the age of 16 years. Two years and 4 months after the trauma, at the age of 19 years, he still had severe right hemiplegia and cognitive dysfunction including aphasia and attention and memory disturbance. Conventional rehabilitation programs cou（d not resolve all of the neuropsychological problems. He started receiving Goshinjo therapy over a period of 22 months. Following the therapy, significant improvements in verbal intelligence quotient （assessed by the Wechsler Adult Intelligence Scale-Third Edition） and attention and concentration function （using the Wechsler Memory Scale-Revised）, and remission of traumatic epilepsy were observed. Goshinjo therapy is suspected to be effective in the treatment of cognitive dysfunction in the chronic stage after severe traumatic brain injury.

Brain and spinal cord trauma:what we know about the therapeutic potential of insulin growth factor 1 gene therapy

Although little attention has been paid to cognitive and emotional dysfunctions observed in patients after spinal co rd injury,several reports have described impairments in cognitive abilities.Our group also has contributed significantly to the study of cognitive impairments in a rat model of spinal co rd injury.These findings are very significant because they demonstrate that cognitive and mood deficits are not induced by lifestyle changes,drugs of abuse,and combined medication.They are related to changes in brain structures involved in cognition and emotion,such as the hippocampus.Chronic spinal cord injury decreases neurogenesis,enhances glial reactivity leading to hippocampal neuroinflammation,and trigge rs cognitive deficits.These brain distal abnormalities are recently called te rtiary damage.Given that there is no treatment for Tertiary Damage,insulin growth factor 1 gene therapy emerges as a good candidate.Insulin growth factor 1 gene thera py recove rs neurogenesis and induces the polarization from pro-inflammato ry towards anti-inflammatory microglial phenotypes,which represents a potential strategy to treat the neuroinflammation that supports te rtiary damage.Insulin growth factor 1 gene therapy can be extended to other central nervous system pathologies such as traumatic brain injury where the neuroinflammatory component is crucial.Insulin growth factor 1 gene therapy could emerge as a new therapeutic strategy for treating traumatic brain injury and spinal cord injury.

Reversible lesions in the brain parenchyma in Wilson's disease confirmed by magnetic resonance imaging:earlier administration of chelating therapy can reduce the damage to the brain

The aim of this study was to evaluate the resolution of brain lesions in patients with Wilson’s disease during the long-term chelating therapy using magnetic resonance imaging and a possible signiifcance of the time latency between the initial symptoms of the disease and the introduction of this therapy. Initial magnetic resonance examination was performed in 37 patients with proven neurological form of Wilson’s disease with cerebellar, parkinsonian and dystonic presentation. Magnetic resonance reexamination was done 5.7 ± 1.3 years later in 14 patients. Patients were divided into： group A, where chelating therapy was initiated 〈 24 months from the ifrst symp-toms and group B, where the therapy started≥ 24 months after the initial symptoms. Symmetry of the lesions was seen in 100% of patients. There was a signiifcant difference between groups A and B regarding complete resolution of brain stem and putaminal lesions （P= 0.005 andP=0.024, respectively）. If the correct diagnosis and adequate treatment are not established less than 24 months after onset of the symptoms, irreversible lesions in the brain parenchyma could be ex-pected. Signal abnormalities on magnetic resonance imaging might therefore, at least in the early stages, represent reversible myelinolisis or cytotoxic edema associated with copper toxicity.

Photodynamic therapy of brain tumors and novel optical coherence tomography strategies for in vivo monitoring of cerebral°uid dynamics

Photodynamic therapy(PDT)is a promising tool for least-invasive alternative methods for the treatment of brain tumors.The newly discovered PDT-induced opening of the blood–brain barrier(BBB)permeability open novel strategies for drug-brain delivery during post-surgical treatment of glioblastoma GBM.Here we discuss mechanisms of PDT-mediated opening of the BBB and age differences in PDT-related increase in BBB permeability,including with formation of brain edema.The meningeal lymphatic system plays a crucial role in the mechanism of brain drainage and clearance from metabolites and toxic molecules.We discuss that noninvasive photonic stimulation of°uid clearance via meningeal lymphatic vessels,and application of optical coherence tomography(OCT)for bed-side monitoring of meningeal lymphatic drainage has the promising perspective to be widely applied in both experimental and clinical studies of PDT and improving guidelines of PDT of brain tumors.

The endogenous progenitor response following traumatic brain injury:a target for cell therapy paradigms

Although there is ample evidence that central nervous system progenitor pools respond to traumatic brain injury,the reported effects are variable and likely contribute to both recovery as well as pathophysiology.Through a better understanding of the diverse progenitor populations in the adult brain and their niche-specific reactions to traumatic insult,treatments can be tailo red to enhance the benefits and dampen the deleterious effects of this response.This review provides an overview of endogenous precursors,the associated effects on cognitive recovery,and the potential of exogenous cell therapeutics to modulate these endogenous repair mechanisms.Beyond the hippocampal dentate gyrus and subventricular zone of the lateral ventricles,more recently identified sites of adult neurogenesis,the meninges,as well as circumventricular organs,are also discussed as targets for endogenous repair.Importantly,this review highlights that progenitor prolife ration alone is no longer a meaningful outcome and studies must strive to better chara cterize precursor spatial localization,transcriptional profile,morphology,and functional synaptic integration.With improved insight and a more targeted approach,the stimulation of endogenous neurogenesis remains a promising strategy for recovery following traumatic brain injury.

Stem cell therapy for COVID-19 and other respiratory diseases:Global trends of clinical trials

Respiratory diseases,including coronavirus disease 2019 and chronic obstructive pulmonary disease(COPD),are leading causes of global fatality.There are no effective and curative treatments,but supportive care only.Cell therapy is a promising therapeutic strategy for refractory and unmanageable pulmonary illnesses,as proved by accumulating preclinical studies.Stem cells consist of totipotent,pluripotent,multipotent,and unipotent cells with the potential to differentiate into cell types requested for repair.Mesenchymal stromal cells,endothelial progenitor cells,peripheral blood stem cells,and lung progenitor cells have been applied to clinical trials.To date,the safety and feasibility of stem cell and extracellular vesicles administration have been confirmed by numerous phase I/II trials in patients with COPD,acute respiratory distress syndrome,bronchial dysplasia,idiopathic pulmonary fibrosis,pulmonary artery hypertension,and silicosis.Five routes and a series of doses have been tested for tolerance and advantages of different regimes.In this review,we systematically summarize the global trends for the cell therapy of common airway and lung diseases registered for clinical trials.The future directions for both new clinical trials and preclinical studies are discussed.

Multi-watt near-infrared light therapy as a neuroregenerative treatment for traumatic brain injury

Infrared light represents a broad spectrum of light with wavelengths from 700 nm to 1 million nm（1,000 microns）.At its shortest wavelengths（referred to as near-infrared）,it merges with the red spectrum of visible light.At the longest end（referred to as far-infrared）,it blends into the range of microwaves.

Modified constraint-induced movement therapy enhances cortical plasticity in a rat model of traumatic brain injury:a resting-state functional MRI study

Modified constraint-induced movement therapy(mCIMT)has shown beneficial effects on motor function improvement after brain injury,but the exact mechanism remains unclear.In this study,amplitude of low frequency fluctuation(ALFF)metrics measured by resting-state functional magnetic resonance imaging was obtained to investigate the efficacy and mechanism of mCIMT in a control co rtical impact(CCI)rat model simulating traumatic brain injury.At 3 days after control co rtical impact model establishment,we found that the mean ALFF(mALFF)signals were decreased in the left motor cortex,somatosensory co rtex,insula cortex and the right motor co rtex,and were increased in the right corpus callosum.After 3 weeks of an 8-hour daily mClMT treatment,the mALFF values were significantly increased in the bilateral hemispheres compared with those at 3 days postoperatively.The mALFF signal valu es of left corpus callosum,left somatosensory cortex,right medial prefro ntal cortex,right motor co rtex,left postero dorsal hippocampus,left motor cortex,right corpus callosum,and right somatosensory cortex were increased in the mCIMT group compared with the control cortical impact group.Finally,we identified brain regions with significantly decreased mALFF valu es at 3 days postoperatively.Pearson correlation coefficients with the right forelimb sliding score indicated that the improvement in motor function of the affected upper limb was associated with an increase in mALFF values in these brain regions.Our findings suggest that functional co rtical plasticity changes after brain injury,and that mCIMT is an effective method to improve affected upper limb motor function by promoting bilateral hemispheric co rtical remodeling.mALFF values correlate with behavio ral changes and can potentially be used as biomarkers to assess dynamic cortical plasticity after traumatic brain injury.

Magnetic resonance imaging and cell-based neurorestorative therapy after brain injury

Restorative cell-based therapies for experimental brain injury, such as stroke and traumatic brain injury,substantially improve functional outcome. We discuss and review state of the art magnetic resonance imaging methodologies and their applications related to cell-based treatment after brain injury. We focus on the potential of magnetic resonance imaging technique and its associated challenges to obtain useful new information related to cell migration, distribution, and quantitation, as well as vascular and neuronal remodeling in response to cell-based therapy after brain injury. The noninvasive nature of imaging might more readily help with translation of cell-based therapy from the laboratory to the clinic.

Adherence to Radiation Therapy among Cervical Cancer Patients at Cancer Diseases Hospital in Lusaka, Zambia

Background: Radiation therapy has the potential to improve cure rates and provide palliative relief for cervical cancer patients. Despite adherence to radiation therapy being a key treatment modality, patients rarely follow prescriptions. Poor adherence to radiation therapy is associated with low survival and high mortality rates. This study therefore sought to investigate the levels of adherence and factors influencing adherence to radiation therapy among cervical cancer patients being treated at Cancer Diseases Hospital. Methods: A cross-sectional analytical study design was used, 142 patients were selected from the outpatient department using a fishbowl sampling method. A structured interview schedule was used to collect data. Data was entered and analyzed using SPSS, the binary logistic regression analysis was used to predict levels of adherence to treatment and to identify factors associated with adherence to RT among cervical cancer patients. Results: The findings showed that 93% of the participants adhered to radiation therapy while 7% did not adhere to treatment. Majority of the patients 77.1% had experienced side effects of radiation therapy. About 28% of patients had severe psychological distress. By using binary logistic regression, there was a statistically significant association between adherence and perceived quality of health care services (p = 0.001). The analysis showed that patients who perceived poor quality of health care services were 0.005 (99.5%) times less likely to adhere to radiation therapy. The other independent variables were not statistically significant despite being associated with adherence among cervical cancer patients. Conclusions and Recommendations: The findings showed that patients who perceived good quality of health care services had higher chances of adherence compared to those who perceived poor quality of health care services. There is therefore a need for quality service provision which could include good maintenance of radiation machines. Furthermore, there is a need to develop guidelines for follow-up in case of any disease outbreak to avoid interference with patients’ treatment schedules and appointments for reviews.

Back to the drawing board:Overview of the next generation of combination therapy for inflammatory bowel disease

Inflammatory bowel disease(IBD)is entering a potentially new era of combined therapeutics.Triantafillidis et al provide an insightful review of the current state of combination therapy,with a focus on the use of a combined biologic and immunomodulator,as well as emerging data on the future potential of dual-biologic therapy(DBT).While current evidence for DBT is limited,encouraging safety profiles and ongoing trials suggest a brighter future for this approach.The importance of controlled trials should be stressed in establishing new treatment paradigms.Ongoing prospective randomized trials of DBT and perhaps future combinations of biologics and small molecule therapies will hopefully guide the next generation of IBD care.

Cell reprogramming therapy for Parkinson’s disease

Parkinson’s disease is typically characterized by the progressive loss of dopaminergic neurons in the substantia nigra pars compacta.Many studies have been performed based on the supplementation of lost dopaminergic neurons to treat Parkinson’s disease.The initial strategy for cell replacement therapy used human fetal ventral midbrain and human embryonic stem cells to treat Parkinson’s disease,which could substantially alleviate the symptoms of Parkinson’s disease in clinical practice.However,ethical issues and tumor formation were limitations of its clinical application.Induced pluripotent stem cells can be acquired without sacrificing human embryos,which eliminates the huge ethical barriers of human stem cell therapy.Another widely considered neuronal regeneration strategy is to directly reprogram fibroblasts and astrocytes into neurons,without the need for intermediate proliferation states,thus avoiding issues of immune rejection and tumor formation.Both induced pluripotent stem cells and direct reprogramming of lineage cells have shown promising results in the treatment of Parkinson’s disease.However,there are also ethical concerns and the risk of tumor formation that need to be addressed.This review highlights the current application status of cell reprogramming in the treatment of Parkinson’s disease,focusing on the use of induced pluripotent stem cells in cell replacement therapy,including preclinical animal models and progress in clinical research.The review also discusses the advancements in direct reprogramming of lineage cells in the treatment of Parkinson’s disease,as well as the controversy surrounding in vivo reprogramming.These findings suggest that cell reprogramming may hold great promise as a potential strategy for treating Parkinson’s disease.

Acupuncture-induced oxygen therapy inhibits oxyradical injury and improves microcirculation following brain injury

BACKGROUND： Acupuncture-induced oxygen therapy combines acupoint theory in traditional Chinese medicine and modern oxygen therapy. Clinical studies have shown that acupuncture-induced oxygen therapy results in favorable outcomes for brain injury. However, the mechanisms of action remain poorly understood. OBJECTIVE： To determine pathological changes and malondialdehyde （MDA） content, superoxide dismutase （SOD） and nitric oxide synthase （NOS） activity, as well as hemorheological brain alterations following acupuncture-induced oxygen therapy, and to explore possible mechanisms of acupuncture-induced oxygen therapy on brain injury. DESIGN, TIME AND SETTING： A randomized, controlled, animal experiment was performed at the Animal Experimental Center of Xi＇an Medical University from January 2006 to April 2009. MATERIALS： An oxygen delivery device, through the use of acupuncture （oxygen delivery machine ＋ silver hollowed needle, 0.5 mm inner diameter）, was purchased from Research Center ol Machine, Shaanxi University of Science and Technology in China. METHODS： A total of 180 Sprague Dawley rats were randomly assigned to six groups （n = 30）： normal, sham-surgery （dura mater exposure）, model （brain injury induced by free-falling of heavy object to head）, Xiantaimixture （0.417 mL/100 g following brain injury）, electroacupuncture [acupuncture at Baihui （DU 20）, Housanfi （ST 36）, Yanglingquan （GB 34）, and Sanyinjiao （SP 6） following brain injury], and acupuncture-induced oxygen therapy （oxygen delivery through hollowed needle to Baihui （DU 20）, Housanfi （ST 36）, Yanglingquan （GB 34）, and Sanyinjiao （SP 6） following brain injury, 0.01 mL/minute）. Group intervention was performed once a day for 14 consecutive days. MAIN OUTCOME MEASURES： Pathological changes, MDA content, SOD and NOS activity, and hemorheological alterations in the brain. RESULTS： Obvious pathological changes were observed, such as hemorrhage, edema, and cell necrosis, following brain injury. These alterations were significantly improved following 14 days of treatment with Xiantai mixture, electroacupuncture, and acupuncture-induced oxygen therapy. In particular, acupuncture-induced oxygen therapy resulted in recovery to normal conditions. In the Xiantai mixture, electroacupuncture, and acupuncture-induced oxygen therapy groups, MDA content was significantly reduced （P 〈 0.01）, SOD activity was significantly increased （P 〈 0.01）, NOS activity was significantly decreased （P 〈 0.01）, and hemorheological indices were reduced, compared with the model group, in particular, acupunture-induced oxygen therapy resulted in the most obvious changes （P 〈 0.01）. CONCLUSION： Acupuncture-induced oxygen therapy improved pathological changes following brain injury by possibly improving blood supply, ameliorating ischemia/hypoxia, and inhibiting peroxidation and free radicals.

Using induced pluripotent stem cells derived neurons to model brain diseases

The ability to use induced pluripotent stem cells（i PSC）to model brain diseases is a powerful tool for unraveling mechanistic alterations in these disorders.Rodent models of brain diseases have spurred understanding of pathology but the concern arises that they may not recapitulate the full spectrum of neuron disruptions associated with human neuropathology.iPSC derived neurons,or other neural cell types,provide the ability to access pathology in cells derived directly from a patient＇s blood sample or skin biopsy where availability of brain tissue is limiting.Thus,utilization of iPSC to study brain diseases provides an unlimited resource for disease modelling but may also be used for drug screening for effective therapies and may potentially be used to regenerate aged or damaged cells in the future.Many brain diseases across the spectrum of neurodevelopment,neurodegenerative and neuropsychiatric are being approached by iPSC models.The goal of an iPSC based disease model is to identify a cellular phenotype that discriminates the disease-bearing cells from the control cells.In this mini-review,the importance of iPSC cell models validated for pluripotency,germline competency and function assessments is discussed.Selected examples for the variety of brain diseases that are being approached by iPSC technology to discover or establish the molecular basis of the neuropathology are discussed.