Botulinum toxin,a protein exotoxin secreted by Clostridium botulinum,binds to peripheral nerve terminals,inhibits acetylcholine release,and leads to flaccid muscle paralysis.[1]Botox(onabotulinum toxin A)was approved ...Botulinum toxin,a protein exotoxin secreted by Clostridium botulinum,binds to peripheral nerve terminals,inhibits acetylcholine release,and leads to flaccid muscle paralysis.[1]Botox(onabotulinum toxin A)was approved by the Food and Drug Administration(FDA)for cosmetic and therapeutic indications in 2002,and its global use has increased substantially.[2]However,some unlicensed botulinum toxin products may cause iatrogenic botulism.[3]Early diagnosis remains challenging owing to non-specific clinical features and the lack of diagnostic biomarkers,often delaying the timely administration of antitoxin.[4]This study reviewed recent cases of botulism in our center and summarized their clinical presentations,symptoms,and outcomes.展开更多
Human brain development is a complex process,and animal models often have significant limitations.To address this,researchers have developed pluripotent stem cell-derived three-dimensional structures,known as brain-li...Human brain development is a complex process,and animal models often have significant limitations.To address this,researchers have developed pluripotent stem cell-derived three-dimensional structures,known as brain-like organoids,to more accurately model early human brain development and disease.To enable more consistent and intuitive reproduction of early brain development,in this study,we incorporated forebrain organoid culture technology into the traditional unguided method of brain organoid culture.This involved embedding organoids in matrigel for only 7 days during the rapid expansion phase of the neural epithelium and then removing them from the matrigel for further cultivation,resulting in a new type of human brain organoid system.This cerebral organoid system replicated the temporospatial characteristics of early human brain development,including neuroepithelium derivation,neural progenitor cell production and maintenance,neuron differentiation and migration,and cortical layer patterning and formation,providing more consistent and reproducible organoids for developmental modeling and toxicology testing.As a proof of concept,we applied the heavy metal cadmium to this newly improved organoid system to test whether it could be used to evaluate the neurotoxicity of environmental toxins.Brain organoids exposed to cadmium for 7 or 14 days manifested severe damage and abnormalities in their neurodevelopmental patterns,including bursts of cortical cell death and premature differentiation.Cadmium exposure caused progressive depletion of neural progenitor cells and loss of organoid integrity,accompanied by compensatory cell proliferation at ectopic locations.The convenience,flexibility,and controllability of this newly developed organoid platform make it a powerful and affordable alternative to animal models for use in neurodevelopmental,neurological,and neurotoxicological studies.展开更多
Dear Editor,We recently reviewed two important studies that investigate the use of botulinum-A toxin(BoNT-A)injections into the bulbospongiosus muscle as a treatment for lifelong premature ejaculation(PE).While both s...Dear Editor,We recently reviewed two important studies that investigate the use of botulinum-A toxin(BoNT-A)injections into the bulbospongiosus muscle as a treatment for lifelong premature ejaculation(PE).While both studies share the goal of evaluating the efficacy and safety of BoNT-A in this context,they reached very different conclusions.The study by Shaher et al.demonstrated significant improvements in ejaculatory latency,indicating that BoNT-A injections may be a helpful treatment for PE.展开更多
Introduction:When conservative treatments fail,botulinum toxin A(BoNT-A)is an option for refractory idiopathic overactive bladder(OAB).This review evaluates the efficacy,safety,and predictive factors for BoNT-A in thi...Introduction:When conservative treatments fail,botulinum toxin A(BoNT-A)is an option for refractory idiopathic overactive bladder(OAB).This review evaluates the efficacy,safety,and predictive factors for BoNT-A in this situation.Material and Methods:A literature search up to January 2025 was performed using PubMed,Google Scholar,and Embase to assess efficacy,safety,and predictors of adverse events(AE)related to BoNT-A.The risk of bias was assessed using the Risk of Bias 2(RoB 2)tool for randomized studies and the Critical Appraisal Skills Programme(CASP)checklist for cohort studies.The quality of the review was evaluated based on the Oxford criteria,following the Strengthening the Assessment of Narrative Review Articles(SANRA)guidelines,and by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses(PRISMA)guidelines for systematic reviews.Results:31 studies were included,involving 5410 patients.BoNT-A improves OAB symptoms even after reinjections.Higher doses do not enhance efficacy but increase AE.AE includes high post-void residual(PVR),clean intermittent self-catheterization(CISC),and Urinary Tract Infection(UTI).Predictors of CISC include age,male gender,hysterectomy,≥3 vaginal deliveries,mixed incontinence,prior mid-urethral sling(MUS),high PVR,low Pressure at Pdet at First Micturition(PIP1)in women,low Bladder Compliance Index(BCI)in men,and high Bladder Outlet Obstruction Index(BOOI).Diabetes and heart failure increase PVR.UTIs are more frequent in women and men with benign prostatic hyperplasia,with CISC increasing the risk fivefold.Severe complications are rare.Predictors of poor response include male gender,high BOOI,low urinary flow,and diabetes.Discussion:BoNT-A is effective for OAB,especially for incontinence.AE is dose-dependent and limits treatment adherence.Their link with poor response remains unclear.Conclusion:BoNT-A effectively treats refractory idiopathic OAB,improving symptoms and quality of life with repeated injections.展开更多
Orofacial muscle hypertonicity,characterized by excessive muscle tension in the facial and masticatory regions,can lead to significant functional impairment and aesthetic concerns.Botulinum toxin type A(BoNT-A),widely...Orofacial muscle hypertonicity,characterized by excessive muscle tension in the facial and masticatory regions,can lead to significant functional impairment and aesthetic concerns.Botulinum toxin type A(BoNT-A),widely known for its cosmetic applications,has emerged as a valuable therapeutic tool in dentistry and maxillofacial medicine.This review explores the pharmacological mechanisms,anatomical considerations,and clinical applications of BoNT-A in the treatment of functional disorders such as bruxism,masseter hypertrophy,temporomandibular joint dysfunction,and facial asymmetry.Emphasis is placed on precision-guided injection techniques,region-specific dosing trends,and formulation-specific performance.Adverse effects,although generally mild and self-limiting,are preventable through anatomical expertise and individualized protocols.Preliminary clinical observations and recent East Asian data suggest variations in the response patterns and optimal dosing strategies.This review also highlights the current gaps,including the need for long-term safety data,standardized training for dental practitioners,and comparative evaluations with non-pharmacological therapies.BoNT-A is a minimally invasive interdisciplinary approach for restoring oral function and facial harmony,supporting its integration into modern dental practice.展开更多
Alga toxins have recently emerged as an environmental risk factor,especially to neurodegenerative diseases,such as Alzheimer's disease,Parkinson's disease and amyotrophic lateral sclerosis.However,the associat...Alga toxins have recently emerged as an environmental risk factor,especially to neurodegenerative diseases,such as Alzheimer's disease,Parkinson's disease and amyotrophic lateral sclerosis.However,the association between the alga toxinsβ-N-methylamino-L-alanine(BMAA),brevetoxin B,cyanoginosin LR,okadaic acid and neurodegenerative diseases remains inadequately investigated.Therefore,the aim of this study was to elucidate the potential associations.Four sets of differentially expressed genes related with BMAA,brevetoxin B,cyanoginosin LR and okadaic acid in Homo sapiens and genes linked to neurodegenerative disease development were respectively collected from the Comparative Toxicogenomic Database.Metascape analysis and cluster community analysis of four alga toxins highlighted protein-protein interaction enrichment and hub genes,while biological processes analysis showed that the dominant pathways involved in harmful effects triggered by four alga toxins were the apoptotic signaling pathway,regulation of amyloid protein formation,inflammatory response and endoplasmic reticulum stress.Genes related to the interactions between four alga toxins and neurodegenerative diseases were selected and analyzed,revealing that the relevant pathways and genes were those involved in apoptotic mitochondrial changes and neuroinflammatory response pathways.The adverse outcome pathway frameworks were constructed according to the analysis results for toxins and associated neurodegenerative diseases.These discoveries provide a new perspective for us to gain a deeper understanding of the neurotoxic effects of four alga toxins.展开更多
Domoic acid(DA),a biotoxin,is produced by several species of marine dinoflagellate and diatom during harmful algal bloom events.DA is a neurotoxin,in humans and non-human primates,oral exposure to DA results in gastro...Domoic acid(DA),a biotoxin,is produced by several species of marine dinoflagellate and diatom during harmful algal bloom events.DA is a neurotoxin,in humans and non-human primates,oral exposure to DA results in gastrointestinal effects,while DA at higher doses leads to neurological symptoms,seizures and memory deficiency.Exposure of humans to DA occurs mainly through consumption of contaminated seafoods containing an accumulation of the toxin.Previously,it was unclear if DA can have toxic effects on the retina.We assessed the toxicity of DA in human retinal cells(ARPE-19)and in zebrafish embryos.DA significantly lowered ARPE-19 cell viability dose-dependently,and decreased anti-oxidative capacity,increased inflammation,and promoted cell death,possibly through modulating the NRF2 and NF-κB signalling pathways.Zebrafish embryos exposed to DA for 4 days from 1 day post fertilization(dpf)had an increase in mortality and a decrease in both hatching and heartbeat rate and exhibited morphological abnormalities.DA treatment also significantly downregulated expression of antioxidant genes and upregulated expression of inflammation mediators,as well as causing photoreceptor death in zebrafish embryos.The results demonstrate that consuming seafood containing DA will have potential toxic effects in human retinas.展开更多
Background:Androgenetic alopecia(AGA)is a common hair loss disorder that significantly affects patient’s quality of life.Botulinum toxin(BoNT)has emerged as a potential treatment;however,its effectiveness and underly...Background:Androgenetic alopecia(AGA)is a common hair loss disorder that significantly affects patient’s quality of life.Botulinum toxin(BoNT)has emerged as a potential treatment;however,its effectiveness and underlying mechanisms remain unclear.This systematic review aimed to synthesize the existing evidence on BoNT for AGA,analyze its mechanisms,evaluate its efficacy,and explore its potential for precision therapy.Methods:A PubMed search was conducted for studies published between 2020 and 2025.A total of 25 studies,including 11 clinical trials and 7 reviews,were included.The studies were analyzed for BoNT mechanisms in AGA,treatment regimens,efficacy,outcomes,cost-effectiveness,and safety profiles.Results:Experimental evidence suggests that BoNT reduces transforming growth factor-βin dermal papilla cells,a key pathological pathway in AGA.Other hypothetical mechanisms,such as scalp muscle relaxation improving microcirculation or inhibiting androgen conversion require further validation.In clinical trials,most studies used 30-150 U of BoNT via intramuscular(six studies)or intradermal(three studies)injections,with 1-3 sessions and up to 6 months of follow-up.Early open-label trials reported response rates of 70%-79%,but recent high-quality randomized controlled trials(RCTs)showed no significant improvement in hair density compared to placebo.Combination therapy with finasteride or minoxidil enhanced treatment outcomes,though large-scale evidence is lacking.BoNT was less cost-effective than first-line therapies such as minoxidil,with session costs approximately 37 times higher.Intramuscular injection appeared more effective than intradermal injection,possibly due to scalp muscle relaxation and vascular decompression.BoNT generally had a mild safety profile.Conclusion:Currently,BoNT lacks robust evidence to replace traditional treatments for AGA.Future research should focus on establishing standardized dosing protocols,conducting large-scale,long-term RCTs,and integrating molecular biomarkers to improve understanding and optimize the clinical use of BoNT in AGA management.展开更多
The integration of phytochemistry into forensic science has emerged as a groundbreaking frontier,providing unprecedented insights into nature's secrets through the precise application of phytochemical fingerprinti...The integration of phytochemistry into forensic science has emerged as a groundbreaking frontier,providing unprecedented insights into nature's secrets through the precise application of phytochemical fingerprinting of phytotoxins as a cutting-edge approach.This study explores the dynamic intersection of phytochemistry and forensic science,highlighting how the unique phytochemical profiles of toxic plants and their secondary metabolites,serve as distinctive markers for forensic investigations.By utilizing advanced techniques such as Ultra-High-Performance Liquid Chromatography(UHPLC)and High-Resolution Mass Spectrometry(HRMS),the detection and quantification of plant-derived are made more accurate in forensic contexts.Real-world case studies are presented to demonstrate the critical role of plant toxins in forensic outcomes and legal proceedings.The challenges,potential,and future prospects of integrating phytochemical fingerprinting of plant toxins into forensic science were discussed.This review aims to illuminate phytochemical fingerprinting of plant toxins as a promising tool to enhance the precision and depth of forensic analyses,offering new insights into the complex stories embedded in plant toxins.展开更多
Nonhuman primates are increasingly being used as animal models in neuroscience research.However,efficient neuronal tracing techniques for labeling motor neurons and primary sensory afferents in the monkey spinal cord ...Nonhuman primates are increasingly being used as animal models in neuroscience research.However,efficient neuronal tracing techniques for labeling motor neurons and primary sensory afferents in the monkey spinal cord are lacking.Here,by injecting the cholera toxin B subunit into the sciatic nerve of a rhesus monkey,we successfully labeled the motor neurons and primary sensory afferents in the lumbar and sacralspinal cord.Labeled alpha motor neurons were located in lamina IX of the L6–S1 segments,which innervate both flexors and extensors.The labeled primary sensory afferents were mainly myelinated Aβfibers that terminated mostly in laminae I and II of the L4–L7 segments.Together with the labeled proprioceptive afferents,the primary sensory afferents formed excitatory synapses with multiple types of spinal neurons.In summary,our methods successfully traced neuronal connections in the monkey spinal cord and can be used in spinal cord studies when nonhuman primates are used.展开更多
AIM:To investigate the therapeutic effects of botulinum toxin A(BTXA)injection versus strabismus surgery in the treatment of acute acquired comitant esotropia(AACE).METHODS:Patient records of AACE cases treated at Fir...AIM:To investigate the therapeutic effects of botulinum toxin A(BTXA)injection versus strabismus surgery in the treatment of acute acquired comitant esotropia(AACE).METHODS:Patient records of AACE cases treated at First People’s Hospital of Nantong from January 2019 to September 2023 were retrospectively analyzed in this study.Patients were categorized into either strabismus surgery or BTXA injection groups based on treatment modality.Further stratification was performed according to preoperative deviation angles[>35 prism diopters(PD)vs≤35 PD]and age(≥18 years adult group vs<18 years adolescent group).The baseline patient characteristics were collected,deviation angles at multiple timepoints before and after treatment were measured,and stereopsis test results were documented.Through comparative analysis of therapeutic outcomes across subgroups,we systematically evaluated the efficacy of different treatment approaches.RESULTS:A total of 43 AACE patients were included.At the final follow-up,both the surgery and BTXA injection groups showed a statistically significant decrease in deviation angle compared to pretreatment measurements(P<0.001).Significant differences were noted between the two groups in terms of the cure rate of strabismus and the recovery rate of stereopsis(P<0.05).For patients with deviations>35 PD,surgery yielded significantly better outcomes than injection therapy in postoperative angle,success rate,and stereopsis recovery(P<0.05).Similarly,in patients aged≥18 years,surgical treatment was superior to injections in reducing strabismus angle,improving success rates,and restoring stereopsis(P<0.05).CONCLUSION:Both BTXA injection and strabismus surgery demonstrate therapeutic efficacy in AACE.Surgical treatment demonstrated superior efficacy compared to BTXA injection therapy,particularly in patients with deviations>35 PD and those aged≥18 years.For patients with angles≤35 PD or under 18 years,BTXA injection remains a viable treatment option.展开更多
T-2 toxin,an omnipresent environmental contaminant,poses a serious risk to the health of humans and animals due to its pronounced cardiotoxicity.This study aimed to elucidate the molecular mechanism of cardiac tissue ...T-2 toxin,an omnipresent environmental contaminant,poses a serious risk to the health of humans and animals due to its pronounced cardiotoxicity.This study aimed to elucidate the molecular mechanism of cardiac tissue damage by T-2 toxin.Twenty-four male Sprague-Dawley rats were orally administered T-2 toxin through gavage for 12 weeks at the dose of 0,10,and 100 nanograms per gram body weight per day(ng/(g·day)),respectively.Morphological,pathological,and ultrastructural alterations in cardiac tissue were meticulously examined.Non-targeted metabolomics analysis was employed to analyze alterations in cardiac metabolites.The expression of the Sirt3/FoxO3α/MnSOD signaling pathway and the level of oxidative stress markers were detected.The results showed that exposure to T-2 toxin elicited myocardial tissue disorders,interstitial hemorrhage,capillary dilation,and fibrotic damage.Mitochondria were markedly impaired,including swelling,fusion,matrix degradation,and membrane damage.Metabonomics analysis unveiled that T-2 toxin could cause alterations in cardiacmetabolic profiles as well as in the Sirt3/FoxO3α/MnSOD signaling pathway.T-2 toxin could inhibit the expressions of the signaling pathway and elevate the level of oxidative stress.In conclusion,the T-2 toxin probably induces cardiac fibrotic impairment by affecting amino acid and choline metabolism as well as up-regulating oxidative stress mediated by the Sirt3/FoxO3α/MnSOD signaling pathway.This study is expected to provide targets for preventing and treating T-2 toxin-induced cardiac fibrotic injury.展开更多
Background:The One Health concept considers the interconnectivity,interactions and interdependence of humans,animals and the environment.Humans,animals and other organisms are constantly exposed to a wide range of nat...Background:The One Health concept considers the interconnectivity,interactions and interdependence of humans,animals and the environment.Humans,animals and other organisms are constantly exposed to a wide range of natural toxins present in the environment.Thus,there is growing concern about the potential detrimental effects that natural toxins could pose to achieve One Health.Interestingly,alkaloids,steroids and bioactive peptides obtained from natural toxins could be used for the development of therapeutic agents.Methodology:Our literature search focused on the following keywords;toxins,One Health,microbial toxins,mycotoxins,phytotoxins,phycotoxins,insect toxins and toxin effects.Google Scholar,Science Direct,PubMed and Web of Science were the search engines used to obtain primary databases.We chose relevant full-text articles and review papers published in English language only.The research was done between July 2022 and January 2023.Results:Natural toxins are poisonous substances comprising bioactive compounds produced by microorganisms,invertebrates,plants and animals.These compounds possess diverse structures and differ in biological function and toxicity,posing risks to human and animal health through the contamination of the environment,causing disease or death in certain cases.Findings from the articles reviewed revealed that effects of natural toxins on animals and humans gained more attention than the impact of natural toxins on the environment and lower organisms,irrespective of the significant roles that lower organisms play to maintain ecosystem balance.Also,systematic approaches for toxin control in the environment and utilization for beneficial purposes are inadequate in many regions.Remarkably,bioactive compounds present in natural toxins have potential for the development of therapeutic agents.These findings suggest that global,comprehensive and coordinated efforts are required for improved management of natural toxins through an interdisciplinary,One Health approach.Conclusion:Adopting a One Health approach is critical to addressing the effects of natural toxins on the health of humans,animals and the environment.展开更多
BACKGROUND Spastic pelvic floor syndrome(SPFS)is a refractory pelvic floor disease characterized by abnormal(uncoordinated)contractions of the external anal sphincter and puborectalis muscle during defecation,resultin...BACKGROUND Spastic pelvic floor syndrome(SPFS)is a refractory pelvic floor disease characterized by abnormal(uncoordinated)contractions of the external anal sphincter and puborectalis muscle during defecation,resulting in rectal emptation and obstructive constipation.The clinical manifestations of SPFS are mainly characterized by difficult defecation,often accompanied by a sense of anal blockage and drooping.Manual defecation is usually needed during defecation.From physical examination,it is commonly observed that the patient's anal muscle tension is high,and it is difficult or even impossible to enter with his fingers.AIM To investigate the characteristics of anorectal pressure and botulinum toxin A injection combined with biofeedback in treating pelvic floor muscle spasm syndrome.METHODS Retrospective analysis of 50 patients diagnosed with pelvic floor spasm syndrome.All patients underwent pelvic floor surface electromyography assessment,anorectal dynamics examination,botulinum toxin type A injection 100 U intramuscular injection,and two cycles of biofeedback therapy.RESULTS After the botulinum toxin A injection combined with two cycles of biofeedback therapy,the patient's postoperative resting and systolic blood pressure were significantly lower than before surgery(P<0.05).Moreover,the electromyography index of the patients in the resting stage and post-resting stages was significantly lower than before surgery(P<0.05).CONCLUSION Botulinum toxin A injection combined with biofeedback can significantly reduce pelvic floor muscle tension in treating pelvic floor muscle spasm syndrome.Anorectal manometry is an effective method to evaluate the efficacy of treatment objectively.However,randomized controlled trials are needed.展开更多
AIM:To investigate botulinum toxin A(BTXA)efficacy on small-angle(≤25Δ)acute acquired concomitant esotropia(AACE)in early-stage patients.METHODS:The electronic medical record data of AACE patients during March 2019 ...AIM:To investigate botulinum toxin A(BTXA)efficacy on small-angle(≤25Δ)acute acquired concomitant esotropia(AACE)in early-stage patients.METHODS:The electronic medical record data of AACE patients during March 2019 and June 2023 were collected in this retrospective and hospital-based cohort study.A total of 72 small-angle AACE patients received BTXA extraocular muscle injection.Patients were grouped by onset-to-treatment time(Group A:≤6mo,Group B:>6mo).Deviation of esotropia,eye alignment and stereopsis were analyzed at the period of pre/post-injection(1wk,1,3,and 6mo).Orthophoria rate at 6mo(horizontal deviation<10Δand binocular single vision)were considered as outcome index.RESULTS:There were no significant baseline differences(P>0.05)between two groups except onset-to-treatment time(2mo vs 11mo,P<0.001).Higher orthophoria rates were in Group A at last follow-up(94.74%vs 73.53%,P=0.013).Post-BTXA deviations of two groups at 1mo showed no difference(P>0.05);while in 3 and 6mo Group A was significantly smaller than group B(all P<0.001).No statistically significant differences were observed among all post-BTXA deviations of near and distance in Group A.In Group B,deviation at 3mo(near:2Δvs 0,P<0.001;distance:4Δvs 0,P<0.001)and 6mo(near:6Δvs 0,P<0.001;distance:6Δvs 0,P<0.001)was significant increased compared to deviation at 1wk after treatment.Group A showed better stereopsis recovery in last follow-up compared to Group B(80″vs 200″,P=0.002).Both groups obtained improved stereopsis after treatment(Group A:80″vs 300″,P<0.001;Group B:200″vs 300″,P=0.037).CONCLUSION:BTXA is effective for AACE with small deviation(≤25Δ)in early stage.Delayed treatment(>6mo)may reduce BTXA efficacy.Early BTXA intervention benefits long-term eye alignment and stereopsis recovery.展开更多
BACKGROUND Neuropathic pain(NP)is the primary symptom of various neurological condi-tions.Patients with NP often experience mood disorders,particularly depression and anxiety,that can severely affect their normal live...BACKGROUND Neuropathic pain(NP)is the primary symptom of various neurological condi-tions.Patients with NP often experience mood disorders,particularly depression and anxiety,that can severely affect their normal lives.Microglial cells are as-sociated with NP.Excessive inflammatory responses,especially the secretion of large amounts of pro-inflammatory cytokines,ultimately lead to neuroinflam-mation.Microglial pyroptosis is a newly discovered form of inflammatory cell death associated with immune responses and inflammation-related diseases of the central nervous system.METHODS Two models,an in vitro lipopolysaccharide(LPS)-stimulated microglial cell model and a selective nerve injury model using BTX-A and SPP1 knockdown treatments,were used.Key proteins in the pyroptosis signaling pathway,NLRP3-GSDMD,were assessed using western blotting,real-time quantitative polymerase chain reaction,and immunofluorescence.Inflammatory factors[interleukin(IL)-6,IL-1β,and tumor necrosis factor(TNF)-α]were assessed using enzyme-linked immuno-sorbent assay.We also evaluated microglial cell proliferation and apoptosis.Furthermore,we measured pain sensation by assessing the delayed hind paw withdrawal latency using thermal stimulation.RESULTS The expression levels of ACS and GSDMD-N and the mRNA expression of TNF-α,IL-6,and IL-1βwere enhanced in LPS-treated microglia.Furthermore,SPP1 expression was also induced in LPS-treated microglia.Notably,BTX-A inhibited SPP1 mRNA and protein expression in the LPS-treated microglia.Additionally,depletion of SPP1 or BTX-A inhibited cell viability and induced apoptosis in LPS-treated microglia,whereas co-treatment with BTX-A enhanced the effect of SPP1 short hairpin(sh)RNA in LPS-treated microglia.Finally,SPP1 depletion or BTX-A treatment reduced the levels of GSDMD-N,NLPRP3,and ASC and suppressed the production of inflammatory factors.CONCLUSION Notably,BTX-A therapy and SPP1 shRNA enhance microglial proliferation and apoptosis and inhibit microglial death.It improves pain perception and inhibits microglial activation in rats with selective nerve pain.展开更多
F-2 toxin is an estrogenic mycotoxin that causes reproductive disorders in animals.Betulinic acid(BA)is a natural pentacyclic lupane-structure triterpenoid that has diverse pharmacological activities.In this study,the...F-2 toxin is an estrogenic mycotoxin that causes reproductive disorders in animals.Betulinic acid(BA)is a natural pentacyclic lupane-structure triterpenoid that has diverse pharmacological activities.In this study,the antioxidative and anti-inflammatory effects of BA and its underlying mechanism are explored in F-2 toxin-triggered mouse ovarian damage.We found that BA alleviated the F-2 toxin-induced ovarian impairment by stimulating follicle growth,reducing inflammatory cell infiltration,repairing damaged mitochondria and endoplasmic reticulum.Simultaneously,BA not only reversed F-2 toxin-induced reduction of follicle stimulating hormone(FSH)and luteinizing hormone(LH)levels in the serum,but also restrained the protein expression of the estrogen receptors a(ERa)and ERβ.Moreover,BA restored the balance of F-2 toxin-induced ovarian redox system disorders.Subsequently,we found that 0.25 mg/kg BA played an anti-inflammatory role in the F-2 toxin-induced ovarian impairment by decreasing interleukin-1β(IL-1β).IL-6,and tumor necrosis factor-α(TNF-α)mRNA expression,as well as inhibiting p38 protein expression.These data demonstrated that BA exerts its protective effect on F-2 toxin-induced ovarian oxidative impairment and inflammation by inhibiting p38 expression,which implies a natural product-based medicine to ameliorate F-2 toxin-caused female reproductive toxicity and provides a detoxifying method for food contaminated by mycotoxin.展开更多
BACKGROUND Nasolabial fold(NLF)depression can affect the facial appearance of patients to some extent and increase their psychological burdens.In recent years,autologous fat grafting(AFG)combined with botulinum toxin ...BACKGROUND Nasolabial fold(NLF)depression can affect the facial appearance of patients to some extent and increase their psychological burdens.In recent years,autologous fat grafting(AFG)combined with botulinum toxin A(BTX-A)injection(AFG+BTX-A injection)has been gradually applied in the treatment of patients with NLF depression.Although studies have been conducted on the efficacy and safety of AFG+BTX-A injection in treating NLF depression,the experimental design,observational indicators,and sample enrollment criteria vary remarkably,making it difficult to draw convincing and consistent conclusions.Thus,further relevant research is warranted.AIM To assess the esthetic improvement,efficacy,and safety of AFG+BTX-A injections in patients with NLF depression.METHODS This study included 60 patients with NLF depression who were treated in our hospital from February 2019 to April 2021.These patients were categorized into control(n=30)and observation(n=30)groups.The observation group received AFG+BTX-A injection,whereas the control group underwent AFG only.All patients were evaluated using the wrinkle severity rating scale(WSRS)and global aesthetic improvement scale.The compactness of facial contours,skin evaluation indexes,adverse reactions,and satisfaction of the two groups were evaluated 3 months postoperatively.RESULTS The WSRS scores of the observation group at 1,3,and 6 months postoperatively were lower than those of the control group(P<0.05).Three months postoperatively,facial fine lines and pores showed obvious improvement and the skin index score was higher in the observation group than in the control group(P<0.05).The compactness of facial contours was better in the observation group than in the control group(P<0.05).In addition,no remarkable differences were noted in the incidence of postoperative adverse reactions such as facial stiffness,facial asymmetry,facial bruising,and facial concavity inequality(P>0.05).CONCLUSION AFG+BTX-A injection is a highly safe,cost-effective,effective,and long-lasting treatment for NLF depression with high esthetic value,which should be promoted in the future.展开更多
Background:Recently,microbotulinum,a new technique that involves injecting botulinum toxin type A(BoNTA)microdroplets into superficial cutaneous tissue,has gained popularity.The precise distribution of BoNTA in the ta...Background:Recently,microbotulinum,a new technique that involves injecting botulinum toxin type A(BoNTA)microdroplets into superficial cutaneous tissue,has gained popularity.The precise distribution of BoNTA in the targeted area profoundly affects outcomes.Many factors may influence the effective area of BoNTA in the dermis.This study aimed to determine the dermal distribution properties of BoNTA to guide microbotulinum injection.Methods:Ten healthy males aged 18–65 years without BoNTA treatment in the previous year were recruited to receive intradermal injections in the chest and back.Ultrasound was used to ensure the intradermal delivery of injections and measure the dermal thickness.The minor iodine starch test was performed at baseline and 3 days,7 days,21 days,1 month,and 2 months after treatment.Results:All participants received intradermal injections.The dermis was thinner on the chest(thickness,0.20±0.03 cm)than on the back(thickness,0.39±0.07 cm)(P<0.05).An injection in the thicker dermis had a significantly smaller effective area at every follow-up visit.The drug concentration did not affect the effective area except at 3 days after treatment.Injection speed did not influence the effective area at any follow-up visits.Conclusion:An injection in a thicker dermis leads to a smaller effective area for intradermal injections.When the BoNTA dose is the same,the drug concentration and injection speed do not matter.展开更多
BACKGROUND Low back pain(LBP)is a prevalent issue that orthopedic surgeons frequently address in the outpatient setting.LBP can arise from various causes,with stiffness in the paraspinal muscles being a notable contri...BACKGROUND Low back pain(LBP)is a prevalent issue that orthopedic surgeons frequently address in the outpatient setting.LBP can arise from various causes,with stiffness in the paraspinal muscles being a notable contributor.The administration of Botulinum toxin type A(BoNT-A)has been found to alleviate back pain by relaxing these stiff muscles.While BoNT-A is approved for use in numerous conditions,a limited number of randomized clinical trials(RCTs)validate its efficacy specifically for treating LBP.AIM To study the safety and the efficacy of BoNT-A in minimizing pain and improving functional outcomes in patients of chronic LBP(CLBP).METHODS In this RCT,adults aged 18-60 years with mechanical LBP persisting for at least six months were enrolled.Participants were allocated to either the Drug group,receiving 200 Ipsen Units(2 mL)of BoNT-A,or the Control group,which received a 2 mL placebo.Over a 2-month follow-up period,both groups were assessed using the Visual Analog Scale(VAS)for pain intensity and the Oswestry Disability Index(ODI)for disability at the start and conclusion of the study.A decrease in pain by 50%was deemed clinically significant.RESULTS The study followed 40 patients for two months,with 20 in each group.A clinically significant reduction in pain was observed in 36 participants.There was a statistically significant decrease in both VAS and ODI scores in the groups at the end of two months.Nonetheless,when comparing the mean score changes,only the reduction in ODI scores(15 in the placebo group vs 16.5 in the drug group,clinically insignificant)was statistically significant(P=0.012),whereas the change in mean VAS scores was not significant(P=0.45).CONCLUSION The study concludes that BoNT-A does not offer a short-term advantage over placebo in reducing pain or improving LBP scores in CLBP patients.展开更多
文摘Botulinum toxin,a protein exotoxin secreted by Clostridium botulinum,binds to peripheral nerve terminals,inhibits acetylcholine release,and leads to flaccid muscle paralysis.[1]Botox(onabotulinum toxin A)was approved by the Food and Drug Administration(FDA)for cosmetic and therapeutic indications in 2002,and its global use has increased substantially.[2]However,some unlicensed botulinum toxin products may cause iatrogenic botulism.[3]Early diagnosis remains challenging owing to non-specific clinical features and the lack of diagnostic biomarkers,often delaying the timely administration of antitoxin.[4]This study reviewed recent cases of botulism in our center and summarized their clinical presentations,symptoms,and outcomes.
基金supported by the National Key R&D Program of China,No.2019YFA0110300(to ZG)the National Natural Science Foundation of China,Nos.81773302(to YF),32070862(to ZG).
文摘Human brain development is a complex process,and animal models often have significant limitations.To address this,researchers have developed pluripotent stem cell-derived three-dimensional structures,known as brain-like organoids,to more accurately model early human brain development and disease.To enable more consistent and intuitive reproduction of early brain development,in this study,we incorporated forebrain organoid culture technology into the traditional unguided method of brain organoid culture.This involved embedding organoids in matrigel for only 7 days during the rapid expansion phase of the neural epithelium and then removing them from the matrigel for further cultivation,resulting in a new type of human brain organoid system.This cerebral organoid system replicated the temporospatial characteristics of early human brain development,including neuroepithelium derivation,neural progenitor cell production and maintenance,neuron differentiation and migration,and cortical layer patterning and formation,providing more consistent and reproducible organoids for developmental modeling and toxicology testing.As a proof of concept,we applied the heavy metal cadmium to this newly improved organoid system to test whether it could be used to evaluate the neurotoxicity of environmental toxins.Brain organoids exposed to cadmium for 7 or 14 days manifested severe damage and abnormalities in their neurodevelopmental patterns,including bursts of cortical cell death and premature differentiation.Cadmium exposure caused progressive depletion of neural progenitor cells and loss of organoid integrity,accompanied by compensatory cell proliferation at ectopic locations.The convenience,flexibility,and controllability of this newly developed organoid platform make it a powerful and affordable alternative to animal models for use in neurodevelopmental,neurological,and neurotoxicological studies.
文摘Dear Editor,We recently reviewed two important studies that investigate the use of botulinum-A toxin(BoNT-A)injections into the bulbospongiosus muscle as a treatment for lifelong premature ejaculation(PE).While both studies share the goal of evaluating the efficacy and safety of BoNT-A in this context,they reached very different conclusions.The study by Shaher et al.demonstrated significant improvements in ejaculatory latency,indicating that BoNT-A injections may be a helpful treatment for PE.
文摘Introduction:When conservative treatments fail,botulinum toxin A(BoNT-A)is an option for refractory idiopathic overactive bladder(OAB).This review evaluates the efficacy,safety,and predictive factors for BoNT-A in this situation.Material and Methods:A literature search up to January 2025 was performed using PubMed,Google Scholar,and Embase to assess efficacy,safety,and predictors of adverse events(AE)related to BoNT-A.The risk of bias was assessed using the Risk of Bias 2(RoB 2)tool for randomized studies and the Critical Appraisal Skills Programme(CASP)checklist for cohort studies.The quality of the review was evaluated based on the Oxford criteria,following the Strengthening the Assessment of Narrative Review Articles(SANRA)guidelines,and by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses(PRISMA)guidelines for systematic reviews.Results:31 studies were included,involving 5410 patients.BoNT-A improves OAB symptoms even after reinjections.Higher doses do not enhance efficacy but increase AE.AE includes high post-void residual(PVR),clean intermittent self-catheterization(CISC),and Urinary Tract Infection(UTI).Predictors of CISC include age,male gender,hysterectomy,≥3 vaginal deliveries,mixed incontinence,prior mid-urethral sling(MUS),high PVR,low Pressure at Pdet at First Micturition(PIP1)in women,low Bladder Compliance Index(BCI)in men,and high Bladder Outlet Obstruction Index(BOOI).Diabetes and heart failure increase PVR.UTIs are more frequent in women and men with benign prostatic hyperplasia,with CISC increasing the risk fivefold.Severe complications are rare.Predictors of poor response include male gender,high BOOI,low urinary flow,and diabetes.Discussion:BoNT-A is effective for OAB,especially for incontinence.AE is dose-dependent and limits treatment adherence.Their link with poor response remains unclear.Conclusion:BoNT-A effectively treats refractory idiopathic OAB,improving symptoms and quality of life with repeated injections.
文摘Orofacial muscle hypertonicity,characterized by excessive muscle tension in the facial and masticatory regions,can lead to significant functional impairment and aesthetic concerns.Botulinum toxin type A(BoNT-A),widely known for its cosmetic applications,has emerged as a valuable therapeutic tool in dentistry and maxillofacial medicine.This review explores the pharmacological mechanisms,anatomical considerations,and clinical applications of BoNT-A in the treatment of functional disorders such as bruxism,masseter hypertrophy,temporomandibular joint dysfunction,and facial asymmetry.Emphasis is placed on precision-guided injection techniques,region-specific dosing trends,and formulation-specific performance.Adverse effects,although generally mild and self-limiting,are preventable through anatomical expertise and individualized protocols.Preliminary clinical observations and recent East Asian data suggest variations in the response patterns and optimal dosing strategies.This review also highlights the current gaps,including the need for long-term safety data,standardized training for dental practitioners,and comparative evaluations with non-pharmacological therapies.BoNT-A is a minimally invasive interdisciplinary approach for restoring oral function and facial harmony,supporting its integration into modern dental practice.
基金supported by the Natural Science Foundation of Shandong province(Nos.ZR2019MH048 and ZR2022QC149)the Double First-class Disciplines Construction Fund Project from Harbin Institute of Technology at Weihai(No.2023SYLHY18)Weihai Science and Technology Development Program。
文摘Alga toxins have recently emerged as an environmental risk factor,especially to neurodegenerative diseases,such as Alzheimer's disease,Parkinson's disease and amyotrophic lateral sclerosis.However,the association between the alga toxinsβ-N-methylamino-L-alanine(BMAA),brevetoxin B,cyanoginosin LR,okadaic acid and neurodegenerative diseases remains inadequately investigated.Therefore,the aim of this study was to elucidate the potential associations.Four sets of differentially expressed genes related with BMAA,brevetoxin B,cyanoginosin LR and okadaic acid in Homo sapiens and genes linked to neurodegenerative disease development were respectively collected from the Comparative Toxicogenomic Database.Metascape analysis and cluster community analysis of four alga toxins highlighted protein-protein interaction enrichment and hub genes,while biological processes analysis showed that the dominant pathways involved in harmful effects triggered by four alga toxins were the apoptotic signaling pathway,regulation of amyloid protein formation,inflammatory response and endoplasmic reticulum stress.Genes related to the interactions between four alga toxins and neurodegenerative diseases were selected and analyzed,revealing that the relevant pathways and genes were those involved in apoptotic mitochondrial changes and neuroinflammatory response pathways.The adverse outcome pathway frameworks were constructed according to the analysis results for toxins and associated neurodegenerative diseases.These discoveries provide a new perspective for us to gain a deeper understanding of the neurotoxic effects of four alga toxins.
基金funded by Namibe UniversityInstituto Nacional de Gestao de Bolsas de Estudo/Angola government through a PhD studentship program+1 种基金the TENOVUS Scotland(S20-02 to Xinhua Shu,the Chief Scientist Office/the RS Macdonald Charitable Trust(SNRF2021 to Xinhua Shu)the Lotus Scholarship Program of Hunan Province,China(2019-23 to Xinhua Shu)。
文摘Domoic acid(DA),a biotoxin,is produced by several species of marine dinoflagellate and diatom during harmful algal bloom events.DA is a neurotoxin,in humans and non-human primates,oral exposure to DA results in gastrointestinal effects,while DA at higher doses leads to neurological symptoms,seizures and memory deficiency.Exposure of humans to DA occurs mainly through consumption of contaminated seafoods containing an accumulation of the toxin.Previously,it was unclear if DA can have toxic effects on the retina.We assessed the toxicity of DA in human retinal cells(ARPE-19)and in zebrafish embryos.DA significantly lowered ARPE-19 cell viability dose-dependently,and decreased anti-oxidative capacity,increased inflammation,and promoted cell death,possibly through modulating the NRF2 and NF-κB signalling pathways.Zebrafish embryos exposed to DA for 4 days from 1 day post fertilization(dpf)had an increase in mortality and a decrease in both hatching and heartbeat rate and exhibited morphological abnormalities.DA treatment also significantly downregulated expression of antioxidant genes and upregulated expression of inflammation mediators,as well as causing photoreceptor death in zebrafish embryos.The results demonstrate that consuming seafood containing DA will have potential toxic effects in human retinas.
文摘Background:Androgenetic alopecia(AGA)is a common hair loss disorder that significantly affects patient’s quality of life.Botulinum toxin(BoNT)has emerged as a potential treatment;however,its effectiveness and underlying mechanisms remain unclear.This systematic review aimed to synthesize the existing evidence on BoNT for AGA,analyze its mechanisms,evaluate its efficacy,and explore its potential for precision therapy.Methods:A PubMed search was conducted for studies published between 2020 and 2025.A total of 25 studies,including 11 clinical trials and 7 reviews,were included.The studies were analyzed for BoNT mechanisms in AGA,treatment regimens,efficacy,outcomes,cost-effectiveness,and safety profiles.Results:Experimental evidence suggests that BoNT reduces transforming growth factor-βin dermal papilla cells,a key pathological pathway in AGA.Other hypothetical mechanisms,such as scalp muscle relaxation improving microcirculation or inhibiting androgen conversion require further validation.In clinical trials,most studies used 30-150 U of BoNT via intramuscular(six studies)or intradermal(three studies)injections,with 1-3 sessions and up to 6 months of follow-up.Early open-label trials reported response rates of 70%-79%,but recent high-quality randomized controlled trials(RCTs)showed no significant improvement in hair density compared to placebo.Combination therapy with finasteride or minoxidil enhanced treatment outcomes,though large-scale evidence is lacking.BoNT was less cost-effective than first-line therapies such as minoxidil,with session costs approximately 37 times higher.Intramuscular injection appeared more effective than intradermal injection,possibly due to scalp muscle relaxation and vascular decompression.BoNT generally had a mild safety profile.Conclusion:Currently,BoNT lacks robust evidence to replace traditional treatments for AGA.Future research should focus on establishing standardized dosing protocols,conducting large-scale,long-term RCTs,and integrating molecular biomarkers to improve understanding and optimize the clinical use of BoNT in AGA management.
文摘The integration of phytochemistry into forensic science has emerged as a groundbreaking frontier,providing unprecedented insights into nature's secrets through the precise application of phytochemical fingerprinting of phytotoxins as a cutting-edge approach.This study explores the dynamic intersection of phytochemistry and forensic science,highlighting how the unique phytochemical profiles of toxic plants and their secondary metabolites,serve as distinctive markers for forensic investigations.By utilizing advanced techniques such as Ultra-High-Performance Liquid Chromatography(UHPLC)and High-Resolution Mass Spectrometry(HRMS),the detection and quantification of plant-derived are made more accurate in forensic contexts.Real-world case studies are presented to demonstrate the critical role of plant toxins in forensic outcomes and legal proceedings.The challenges,potential,and future prospects of integrating phytochemical fingerprinting of plant toxins into forensic science were discussed.This review aims to illuminate phytochemical fingerprinting of plant toxins as a promising tool to enhance the precision and depth of forensic analyses,offering new insights into the complex stories embedded in plant toxins.
基金supported by a grant from Ministry of Science and Technology China,No.2022ZD0204704(to WW)the National Natural Science Foundation of China,No.82301572(to XZ)the China Postdoctoral Science Foundation,No.2023M731202(to XZ)。
文摘Nonhuman primates are increasingly being used as animal models in neuroscience research.However,efficient neuronal tracing techniques for labeling motor neurons and primary sensory afferents in the monkey spinal cord are lacking.Here,by injecting the cholera toxin B subunit into the sciatic nerve of a rhesus monkey,we successfully labeled the motor neurons and primary sensory afferents in the lumbar and sacralspinal cord.Labeled alpha motor neurons were located in lamina IX of the L6–S1 segments,which innervate both flexors and extensors.The labeled primary sensory afferents were mainly myelinated Aβfibers that terminated mostly in laminae I and II of the L4–L7 segments.Together with the labeled proprioceptive afferents,the primary sensory afferents formed excitatory synapses with multiple types of spinal neurons.In summary,our methods successfully traced neuronal connections in the monkey spinal cord and can be used in spinal cord studies when nonhuman primates are used.
文摘AIM:To investigate the therapeutic effects of botulinum toxin A(BTXA)injection versus strabismus surgery in the treatment of acute acquired comitant esotropia(AACE).METHODS:Patient records of AACE cases treated at First People’s Hospital of Nantong from January 2019 to September 2023 were retrospectively analyzed in this study.Patients were categorized into either strabismus surgery or BTXA injection groups based on treatment modality.Further stratification was performed according to preoperative deviation angles[>35 prism diopters(PD)vs≤35 PD]and age(≥18 years adult group vs<18 years adolescent group).The baseline patient characteristics were collected,deviation angles at multiple timepoints before and after treatment were measured,and stereopsis test results were documented.Through comparative analysis of therapeutic outcomes across subgroups,we systematically evaluated the efficacy of different treatment approaches.RESULTS:A total of 43 AACE patients were included.At the final follow-up,both the surgery and BTXA injection groups showed a statistically significant decrease in deviation angle compared to pretreatment measurements(P<0.001).Significant differences were noted between the two groups in terms of the cure rate of strabismus and the recovery rate of stereopsis(P<0.05).For patients with deviations>35 PD,surgery yielded significantly better outcomes than injection therapy in postoperative angle,success rate,and stereopsis recovery(P<0.05).Similarly,in patients aged≥18 years,surgical treatment was superior to injections in reducing strabismus angle,improving success rates,and restoring stereopsis(P<0.05).CONCLUSION:Both BTXA injection and strabismus surgery demonstrate therapeutic efficacy in AACE.Surgical treatment demonstrated superior efficacy compared to BTXA injection therapy,particularly in patients with deviations>35 PD and those aged≥18 years.For patients with angles≤35 PD or under 18 years,BTXA injection remains a viable treatment option.
基金supported by the National Natural Science Foundation of China(No.81872567).
文摘T-2 toxin,an omnipresent environmental contaminant,poses a serious risk to the health of humans and animals due to its pronounced cardiotoxicity.This study aimed to elucidate the molecular mechanism of cardiac tissue damage by T-2 toxin.Twenty-four male Sprague-Dawley rats were orally administered T-2 toxin through gavage for 12 weeks at the dose of 0,10,and 100 nanograms per gram body weight per day(ng/(g·day)),respectively.Morphological,pathological,and ultrastructural alterations in cardiac tissue were meticulously examined.Non-targeted metabolomics analysis was employed to analyze alterations in cardiac metabolites.The expression of the Sirt3/FoxO3α/MnSOD signaling pathway and the level of oxidative stress markers were detected.The results showed that exposure to T-2 toxin elicited myocardial tissue disorders,interstitial hemorrhage,capillary dilation,and fibrotic damage.Mitochondria were markedly impaired,including swelling,fusion,matrix degradation,and membrane damage.Metabonomics analysis unveiled that T-2 toxin could cause alterations in cardiacmetabolic profiles as well as in the Sirt3/FoxO3α/MnSOD signaling pathway.T-2 toxin could inhibit the expressions of the signaling pathway and elevate the level of oxidative stress.In conclusion,the T-2 toxin probably induces cardiac fibrotic impairment by affecting amino acid and choline metabolism as well as up-regulating oxidative stress mediated by the Sirt3/FoxO3α/MnSOD signaling pathway.This study is expected to provide targets for preventing and treating T-2 toxin-induced cardiac fibrotic injury.
基金supported by The Africa Education Initiative(NEF),USA and the National Veterinary Research Institute Vom,Nigeria.
文摘Background:The One Health concept considers the interconnectivity,interactions and interdependence of humans,animals and the environment.Humans,animals and other organisms are constantly exposed to a wide range of natural toxins present in the environment.Thus,there is growing concern about the potential detrimental effects that natural toxins could pose to achieve One Health.Interestingly,alkaloids,steroids and bioactive peptides obtained from natural toxins could be used for the development of therapeutic agents.Methodology:Our literature search focused on the following keywords;toxins,One Health,microbial toxins,mycotoxins,phytotoxins,phycotoxins,insect toxins and toxin effects.Google Scholar,Science Direct,PubMed and Web of Science were the search engines used to obtain primary databases.We chose relevant full-text articles and review papers published in English language only.The research was done between July 2022 and January 2023.Results:Natural toxins are poisonous substances comprising bioactive compounds produced by microorganisms,invertebrates,plants and animals.These compounds possess diverse structures and differ in biological function and toxicity,posing risks to human and animal health through the contamination of the environment,causing disease or death in certain cases.Findings from the articles reviewed revealed that effects of natural toxins on animals and humans gained more attention than the impact of natural toxins on the environment and lower organisms,irrespective of the significant roles that lower organisms play to maintain ecosystem balance.Also,systematic approaches for toxin control in the environment and utilization for beneficial purposes are inadequate in many regions.Remarkably,bioactive compounds present in natural toxins have potential for the development of therapeutic agents.These findings suggest that global,comprehensive and coordinated efforts are required for improved management of natural toxins through an interdisciplinary,One Health approach.Conclusion:Adopting a One Health approach is critical to addressing the effects of natural toxins on the health of humans,animals and the environment.
文摘BACKGROUND Spastic pelvic floor syndrome(SPFS)is a refractory pelvic floor disease characterized by abnormal(uncoordinated)contractions of the external anal sphincter and puborectalis muscle during defecation,resulting in rectal emptation and obstructive constipation.The clinical manifestations of SPFS are mainly characterized by difficult defecation,often accompanied by a sense of anal blockage and drooping.Manual defecation is usually needed during defecation.From physical examination,it is commonly observed that the patient's anal muscle tension is high,and it is difficult or even impossible to enter with his fingers.AIM To investigate the characteristics of anorectal pressure and botulinum toxin A injection combined with biofeedback in treating pelvic floor muscle spasm syndrome.METHODS Retrospective analysis of 50 patients diagnosed with pelvic floor spasm syndrome.All patients underwent pelvic floor surface electromyography assessment,anorectal dynamics examination,botulinum toxin type A injection 100 U intramuscular injection,and two cycles of biofeedback therapy.RESULTS After the botulinum toxin A injection combined with two cycles of biofeedback therapy,the patient's postoperative resting and systolic blood pressure were significantly lower than before surgery(P<0.05).Moreover,the electromyography index of the patients in the resting stage and post-resting stages was significantly lower than before surgery(P<0.05).CONCLUSION Botulinum toxin A injection combined with biofeedback can significantly reduce pelvic floor muscle tension in treating pelvic floor muscle spasm syndrome.Anorectal manometry is an effective method to evaluate the efficacy of treatment objectively.However,randomized controlled trials are needed.
基金Supported by Key Research and Development Program of Hubei Province(No.2022BCA044)the Central Guided Local Science and Technology Development(No.2019ZYYD058).
文摘AIM:To investigate botulinum toxin A(BTXA)efficacy on small-angle(≤25Δ)acute acquired concomitant esotropia(AACE)in early-stage patients.METHODS:The electronic medical record data of AACE patients during March 2019 and June 2023 were collected in this retrospective and hospital-based cohort study.A total of 72 small-angle AACE patients received BTXA extraocular muscle injection.Patients were grouped by onset-to-treatment time(Group A:≤6mo,Group B:>6mo).Deviation of esotropia,eye alignment and stereopsis were analyzed at the period of pre/post-injection(1wk,1,3,and 6mo).Orthophoria rate at 6mo(horizontal deviation<10Δand binocular single vision)were considered as outcome index.RESULTS:There were no significant baseline differences(P>0.05)between two groups except onset-to-treatment time(2mo vs 11mo,P<0.001).Higher orthophoria rates were in Group A at last follow-up(94.74%vs 73.53%,P=0.013).Post-BTXA deviations of two groups at 1mo showed no difference(P>0.05);while in 3 and 6mo Group A was significantly smaller than group B(all P<0.001).No statistically significant differences were observed among all post-BTXA deviations of near and distance in Group A.In Group B,deviation at 3mo(near:2Δvs 0,P<0.001;distance:4Δvs 0,P<0.001)and 6mo(near:6Δvs 0,P<0.001;distance:6Δvs 0,P<0.001)was significant increased compared to deviation at 1wk after treatment.Group A showed better stereopsis recovery in last follow-up compared to Group B(80″vs 200″,P=0.002).Both groups obtained improved stereopsis after treatment(Group A:80″vs 300″,P<0.001;Group B:200″vs 300″,P=0.037).CONCLUSION:BTXA is effective for AACE with small deviation(≤25Δ)in early stage.Delayed treatment(>6mo)may reduce BTXA efficacy.Early BTXA intervention benefits long-term eye alignment and stereopsis recovery.
文摘BACKGROUND Neuropathic pain(NP)is the primary symptom of various neurological condi-tions.Patients with NP often experience mood disorders,particularly depression and anxiety,that can severely affect their normal lives.Microglial cells are as-sociated with NP.Excessive inflammatory responses,especially the secretion of large amounts of pro-inflammatory cytokines,ultimately lead to neuroinflam-mation.Microglial pyroptosis is a newly discovered form of inflammatory cell death associated with immune responses and inflammation-related diseases of the central nervous system.METHODS Two models,an in vitro lipopolysaccharide(LPS)-stimulated microglial cell model and a selective nerve injury model using BTX-A and SPP1 knockdown treatments,were used.Key proteins in the pyroptosis signaling pathway,NLRP3-GSDMD,were assessed using western blotting,real-time quantitative polymerase chain reaction,and immunofluorescence.Inflammatory factors[interleukin(IL)-6,IL-1β,and tumor necrosis factor(TNF)-α]were assessed using enzyme-linked immuno-sorbent assay.We also evaluated microglial cell proliferation and apoptosis.Furthermore,we measured pain sensation by assessing the delayed hind paw withdrawal latency using thermal stimulation.RESULTS The expression levels of ACS and GSDMD-N and the mRNA expression of TNF-α,IL-6,and IL-1βwere enhanced in LPS-treated microglia.Furthermore,SPP1 expression was also induced in LPS-treated microglia.Notably,BTX-A inhibited SPP1 mRNA and protein expression in the LPS-treated microglia.Additionally,depletion of SPP1 or BTX-A inhibited cell viability and induced apoptosis in LPS-treated microglia,whereas co-treatment with BTX-A enhanced the effect of SPP1 short hairpin(sh)RNA in LPS-treated microglia.Finally,SPP1 depletion or BTX-A treatment reduced the levels of GSDMD-N,NLPRP3,and ASC and suppressed the production of inflammatory factors.CONCLUSION Notably,BTX-A therapy and SPP1 shRNA enhance microglial proliferation and apoptosis and inhibit microglial death.It improves pain perception and inhibits microglial activation in rats with selective nerve pain.
基金supported by the National Natural Science Foundation of China (32273084)the Special Funds for Construction of Innovative Provinces in Hunan Province,China (2020NK2032)+2 种基金the Natural Science Foundation of Hunan Province,China (2020JJ4368)Innovation Foundation for Postgraduate of Hunan Province,China (CX20220670)Innovation Foundation for Postgraduate of Hunan Agricultural University,China (2022XC010)。
文摘F-2 toxin is an estrogenic mycotoxin that causes reproductive disorders in animals.Betulinic acid(BA)is a natural pentacyclic lupane-structure triterpenoid that has diverse pharmacological activities.In this study,the antioxidative and anti-inflammatory effects of BA and its underlying mechanism are explored in F-2 toxin-triggered mouse ovarian damage.We found that BA alleviated the F-2 toxin-induced ovarian impairment by stimulating follicle growth,reducing inflammatory cell infiltration,repairing damaged mitochondria and endoplasmic reticulum.Simultaneously,BA not only reversed F-2 toxin-induced reduction of follicle stimulating hormone(FSH)and luteinizing hormone(LH)levels in the serum,but also restrained the protein expression of the estrogen receptors a(ERa)and ERβ.Moreover,BA restored the balance of F-2 toxin-induced ovarian redox system disorders.Subsequently,we found that 0.25 mg/kg BA played an anti-inflammatory role in the F-2 toxin-induced ovarian impairment by decreasing interleukin-1β(IL-1β).IL-6,and tumor necrosis factor-α(TNF-α)mRNA expression,as well as inhibiting p38 protein expression.These data demonstrated that BA exerts its protective effect on F-2 toxin-induced ovarian oxidative impairment and inflammation by inhibiting p38 expression,which implies a natural product-based medicine to ameliorate F-2 toxin-caused female reproductive toxicity and provides a detoxifying method for food contaminated by mycotoxin.
基金Supported by Medical and Health Science and Technology Project of Hangzhou,No.B20230855Hangzhou Science and Technology Plan Development Project,No.20210133X01.
文摘BACKGROUND Nasolabial fold(NLF)depression can affect the facial appearance of patients to some extent and increase their psychological burdens.In recent years,autologous fat grafting(AFG)combined with botulinum toxin A(BTX-A)injection(AFG+BTX-A injection)has been gradually applied in the treatment of patients with NLF depression.Although studies have been conducted on the efficacy and safety of AFG+BTX-A injection in treating NLF depression,the experimental design,observational indicators,and sample enrollment criteria vary remarkably,making it difficult to draw convincing and consistent conclusions.Thus,further relevant research is warranted.AIM To assess the esthetic improvement,efficacy,and safety of AFG+BTX-A injections in patients with NLF depression.METHODS This study included 60 patients with NLF depression who were treated in our hospital from February 2019 to April 2021.These patients were categorized into control(n=30)and observation(n=30)groups.The observation group received AFG+BTX-A injection,whereas the control group underwent AFG only.All patients were evaluated using the wrinkle severity rating scale(WSRS)and global aesthetic improvement scale.The compactness of facial contours,skin evaluation indexes,adverse reactions,and satisfaction of the two groups were evaluated 3 months postoperatively.RESULTS The WSRS scores of the observation group at 1,3,and 6 months postoperatively were lower than those of the control group(P<0.05).Three months postoperatively,facial fine lines and pores showed obvious improvement and the skin index score was higher in the observation group than in the control group(P<0.05).The compactness of facial contours was better in the observation group than in the control group(P<0.05).In addition,no remarkable differences were noted in the incidence of postoperative adverse reactions such as facial stiffness,facial asymmetry,facial bruising,and facial concavity inequality(P>0.05).CONCLUSION AFG+BTX-A injection is a highly safe,cost-effective,effective,and long-lasting treatment for NLF depression with high esthetic value,which should be promoted in the future.
基金supported by the National High Level Hospital Clinical Research Funding(grant nos.2022-PUMCH-B-041,2022-PUMCH-A-210,and 2022-PUMCH-C-025).
文摘Background:Recently,microbotulinum,a new technique that involves injecting botulinum toxin type A(BoNTA)microdroplets into superficial cutaneous tissue,has gained popularity.The precise distribution of BoNTA in the targeted area profoundly affects outcomes.Many factors may influence the effective area of BoNTA in the dermis.This study aimed to determine the dermal distribution properties of BoNTA to guide microbotulinum injection.Methods:Ten healthy males aged 18–65 years without BoNTA treatment in the previous year were recruited to receive intradermal injections in the chest and back.Ultrasound was used to ensure the intradermal delivery of injections and measure the dermal thickness.The minor iodine starch test was performed at baseline and 3 days,7 days,21 days,1 month,and 2 months after treatment.Results:All participants received intradermal injections.The dermis was thinner on the chest(thickness,0.20±0.03 cm)than on the back(thickness,0.39±0.07 cm)(P<0.05).An injection in the thicker dermis had a significantly smaller effective area at every follow-up visit.The drug concentration did not affect the effective area except at 3 days after treatment.Injection speed did not influence the effective area at any follow-up visits.Conclusion:An injection in a thicker dermis leads to a smaller effective area for intradermal injections.When the BoNTA dose is the same,the drug concentration and injection speed do not matter.
基金Supported by All India Institute of Medical Sciences Bhubaneswar Research Grant,No.AIIMS/BBSR/RS/2022/372.
文摘BACKGROUND Low back pain(LBP)is a prevalent issue that orthopedic surgeons frequently address in the outpatient setting.LBP can arise from various causes,with stiffness in the paraspinal muscles being a notable contributor.The administration of Botulinum toxin type A(BoNT-A)has been found to alleviate back pain by relaxing these stiff muscles.While BoNT-A is approved for use in numerous conditions,a limited number of randomized clinical trials(RCTs)validate its efficacy specifically for treating LBP.AIM To study the safety and the efficacy of BoNT-A in minimizing pain and improving functional outcomes in patients of chronic LBP(CLBP).METHODS In this RCT,adults aged 18-60 years with mechanical LBP persisting for at least six months were enrolled.Participants were allocated to either the Drug group,receiving 200 Ipsen Units(2 mL)of BoNT-A,or the Control group,which received a 2 mL placebo.Over a 2-month follow-up period,both groups were assessed using the Visual Analog Scale(VAS)for pain intensity and the Oswestry Disability Index(ODI)for disability at the start and conclusion of the study.A decrease in pain by 50%was deemed clinically significant.RESULTS The study followed 40 patients for two months,with 20 in each group.A clinically significant reduction in pain was observed in 36 participants.There was a statistically significant decrease in both VAS and ODI scores in the groups at the end of two months.Nonetheless,when comparing the mean score changes,only the reduction in ODI scores(15 in the placebo group vs 16.5 in the drug group,clinically insignificant)was statistically significant(P=0.012),whereas the change in mean VAS scores was not significant(P=0.45).CONCLUSION The study concludes that BoNT-A does not offer a short-term advantage over placebo in reducing pain or improving LBP scores in CLBP patients.
