BACKGROUND The previous studies have primarily focused on the influence of botulinum toxin A(BoNT-A)injection on emotions during the period of peak motor symptom improvement in blepharospasm patients,based on facial f...BACKGROUND The previous studies have primarily focused on the influence of botulinum toxin A(BoNT-A)injection on emotions during the period of peak motor symptom improvement in blepharospasm patients,based on facial feedback hypothesis.AIM To evaluate the sustained anxiolytic and antidepressant effects of BoNT-A in blepharospasm patients beyond motor symptom control.METHODS We recruited benign essential blepharospasm patients with BoNT-A treatment and collected their data to compare scale scores of Jankovic Rating Scale,Blepharospasm Disability Index,Self-rating Anxiety Scale(SAS),Self-rating Depression Scale(SDS),Hamilton Anxiety Scale and Hamilton Depression Scale between pretreatment(baseline)and pre-reinjection(treatment),to further assess the effects of repeated treatments with BoNT by using sub-group analyses in the certain special states.RESULTS A total of 21 eligible blepharospasm patients were with the mean age of 58.4 years and a male-to-female ratio of 1:6.Significantly decreases in the subscale scores of SDS and SAS,including SDS well-being index,decreased capacity and hard to decide,SAS inability to sit still and headache were showed at post-a single BoNT-A injection when scale scores of Jankovic Rating Scale and Blepharospasm Disability Index were matched between baseline and posttreatment.With each additional BoNT-A injection,the odds ratio of patients with the moderate depressive symptoms decreased by 92.6%.Moreover,BoNT treatment remained a decrease in the subscale scores of SDS and SAS in patients with repeated injections.CONCLUSION This study is to demonstrate that repeated BoNT-A injection have a long-lasting relief for anxiety and depressive symptoms in blepharospasm even after its motor symptom-modulating effects have diminished.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
Botulinum toxin A （BTXA） has been used in several clinical trials to treat excessive glandular secretion; however, the precise mechanism of its action on the secretory function of salivary gland has not been fully e...Botulinum toxin A （BTXA） has been used in several clinical trials to treat excessive glandular secretion; however, the precise mechanism of its action on the secretory function of salivary gland has not been fully elucidated. In this study, we aimed to investigate the effect of BTXA on secretion of submandibular gland in rabbits and to identify its mechanism of action on the secretory function of salivary gland. At 12 weeks after injection with 5 units of BTXA, we found a significant decrease in the saliva flow from submandibular glands, while the salivary amylase concentration increased. Morphological analysis revealed reduction in the size of acinar cells with intracellular accumulation of secretory granules that coalesced to form a large ovoid structure. Expression of M3-muscarinic acetylcholine receptor （M3 receptor） and aquaporin-5 （AQP5） mRNA decreased after BTXA treatment, and distribution of AQP5 in the apical membrane was reduced at 1, 2 and 4 weeks after BTXA injection. Furthermore, BTXA injection was found to induce apoptosis of acini. These results indicate that BTXA decreases the fluid secretion of submandibular glands and increases the concentration of amylase in saliva. Decreased expression of M3 receptor and AQP5, inhibition of AQP5 translocation, and cell apoptosis might involve in BTXA-reduced fluid secretion of submandibular lands.展开更多
Clostridioides difficile(C.difficile)is the most common pathogen causing health care-associated infections.C.difficile TcdA and TcdB have been shown to activate enteric neurons;however,what population of these cells i...Clostridioides difficile(C.difficile)is the most common pathogen causing health care-associated infections.C.difficile TcdA and TcdB have been shown to activate enteric neurons;however,what population of these cells is more profoundly influenced and the mechanism underlying these effects remain unknown.AIM To characterize a specific population of TcdA-affected myenteric neurons and investigate the role of the P2X7 receptor in TcdA-induced ileal inflammation,cell death,and the changes in the enteric nervous system in mice.METHODS Swiss mice were used to model TcdA-induced ileitis in ileal loops exposed to TcdA(50μg/Loop)for 4 h.To investigate the role of the P2X7 receptor,Brilliant Blue G(50 mg/kg,i.p.),which is a nonspecific P2X7 receptor antagonist,or A438079(0.7μg/mouse,i.p.),which is a competitive P2X7 receptor antagonist,were injected one hour prior to TcdA challenge.Ileal samples were collected to analyze the expression of the P2X7 receptor(by quantitative real-time polymerase chain reaction and immunohistochemistry),the population of myenteric enteric neurons(immunofluorescence),histological damage,intestinal inflammation,cell death(terminal deoxynucleotidyltransferasemediated dUTP-biotin nick end labeling),neuronal loss,and S100B synthesis(immunohistochemistry).RESULTS TcdA upregulated(P<0.05)the expression of the P2X7 receptor gene in the ileal tissues,increasing the level of this receptor in myenteric neurons compared to that in control mice.Comparison with the control mice indicated that TcdA promoted(P<0.05)the loss of myenteric calretinin+(Calr)and choline acetyltransferase+neurons and increased the number of nitrergic+and Calr+neurons expressing the P2X7 receptor.Blockade of the P2X7 receptor decreased TcdAinduced intestinal damage,cytokine release[interleukin(IL)-1β,IL-6,IL-8,and tumor necrosis factor-α],cell death,enteric neuron loss,and S100B synthesis in the mouse ileum.CONCLUSION Our findings demonstrated that TcdA induced the upregulation of the P2X7 receptor,which promoted enteric neuron loss,S100B synthesis,tissue damage,inflammation,and cell death in the mouse ileum.These findings contribute to the future directions in understanding the mechanism involved in intestinal dysfunction reported in patients after C.difficile infection.展开更多
More than 70% children with cerebral palsy belong to the spastic one, and the increased muscular tension results in motor dysfunction and posture abnormality. OBJECTIVE： To observe the assistant effect of the local i...More than 70% children with cerebral palsy belong to the spastic one, and the increased muscular tension results in motor dysfunction and posture abnormality. OBJECTIVE： To observe the assistant effect of the local injection of BTX-A at multiple points in the rehabilitative treatment of spastic cerebral palsy. DESIGN： A comparative observation on the clinical efficacy. SETTINGS： Rehabilitation Center, Loufeng Hospital, Suzhou Industrial Park; Gansu Rehabilitation Center Hospital. PARTICIPANTS： Sixty-nine children with cerebral palsy were selected from the outpatients and inpatients who accepted rehabilitative treatments in the Cerebral Palsy Treatment Center of Gansu Rehabilitation Center Hospital from April 2003 and October 2004. Inclusive criteria： ①Having high risk factors for brain injury before birth and within 1 month after birth, mainly manifested as central motor disorder and posture abnormality; ② Accompanied by increase of muscular tension in both lower limbs, appearing as tiptoes and scissors gaits while in standing position or walking; ③ Without fixed contracture of lower limb; ④ Had never been operated for lower limbs; ⑤ Had never been injected with BTX-A; ⑥ Clearly diagnosed to have spastic palsy. The enrolled children were not screened by disease conditions, course, age, etc., and informed consents were obtained from the parents of all the children. The children whose parents agreed to accept BTX-A treatment were taken as BTX-A treated group （n =45）, and the others as control group （n = 24）. METHODS： All the children accepted regular rehabilitative training after admission, 6 times a weeks, besides, those in the BTX-A treated group were given local injection of BTX-A at multiple points of target muscles, including bilateral adductor longus muscles, pectineal muscles, gastrocnemius muscles and soleus muscles. BTX-A was diluted with saline （5 U BTX-A in 0.1 mL）, 3 - 4 U/kg for each piece of muscle. The number of injected sites depended on the size of target muscle, and no more than 0.5 mL for each site. The injection should be followed by manual massage for 1 - 2 minutes, and electromuscular stimulation for 20 minutes, which were continued for 3 days. They participated in the comprehensive rehabilitative training and treatment at 24 hours after injection. MAIN OUTCOME MEASURES： The comprehensive abilities of cerebral palsy were evaluated, the adductor angle and forced area on soles were measured before treatment and at 3 and 6 months after treatment. RESULTS： All the 69 children with spastic cerebral palsy were involved in the analysis of results. ① Efficacy in the BTX-A treated group： BTX-A began to take effect at 48 hours after injection, and the maximal effect was observed in all the cases on the 6th day; 2 weeks later, the scissors gaits and hip adduction were obviously improved in 39 and 11 cases, respectively, and tiptoes gaits were improved in 22 cases; 2 months later, tiptoes gaits were improved in 43 cases. ② Efficacy in the control group： Two months later, certain improvements of scissors gaits were observed in 2 children with mild cerebral palsy; the scissors gaits and tiptoes were obviously improved in 6 cases of moderate cerebral palsy and 3 cases of mild one after 3 months, and there were changes of the parameters after 6 months in 1, 10 and 5 cases of severe, moderate and mild cerebral palsy, respectively. ③ Improvement of adductor angle before and after treatment in both groups： The muscular tension was evaluated according to Komam＇s method. There was no obvious difference in the adductor angle between the two groups before treatment （P 〉 0.05）. The adductor angle had very significant difference （P 〈 0.01） and significant difference （P 〈 0.05） between the two groups at 3 and 6 months after treatment. ④ Changes of forced area on soles before and after treatment in bothgroups： The forced area on soles was assessed referred to the method of foot-print analysis. There was no obvious difference in the forced area on soles between the two groups before treatment （P 〉 0.05）. The forced area on soles had very significant difference （P 〈 0.01） and significant difference （P 〈 0.05） between the two groups at 3 and 6 months after treatment. CONCLUSION： BTX-A local injection is an important assistant therapeutic method for treating spastic cerebral palsy. For the patients with moderate and severe cerebral palsy, BTX-A local injection should be combined with rehabilitative training to obviously shorten the course and improve efficacy.展开更多
Diphtheria toxin A （DTA）, a segment of the diphtheria toxin （tox）, inhibits protein synthesis in cells. When released from a cell, DTA is nontoxic and cannot enter other cells independently without the help of dip...Diphtheria toxin A （DTA）, a segment of the diphtheria toxin （tox）, inhibits protein synthesis in cells. When released from a cell, DTA is nontoxic and cannot enter other cells independently without the help of diphtheria toxin B. In this study, we artificially synthesized the DTA gene sequence and cloned it into pEGFP-N1 to generate the recombinant vector pEGFP-N1-DTA. This recombinant vector was then transfected into 293T cells to observe the effect of DTA protein expression on enhanced green fluorescent protein （EGFP） protein expression and the proliferation of 293T cells. After 48 h, high levels of EGFP expression were seen in control pEGFP-Nl-transfected cells, whereas very low levels were seen in cells transfected with pEGFP-N1-DTA. Reverse transcription polymerase chain reaction confirmed the expression of the DTA gene in cells transfected with pEGFP-N^-DTA. Further, the 3-（4,5-dimethylthiazol-2-yl）-2,5-diphenyltetrazolium bromide （M-I-I-） assay revealed a significant difference in cell proliferation between the control group and the pEGFP-N1-DTA-transfected group. Using the expression of EGFP expression as an indicator, this study revealed that DTA expression can inhibit intracellular protein synthesis and cell proliferation.展开更多
Objective: To study the effects of recombinant expression vector containing human breast cancer DF3 promotor and diphtheria toxin A fragment on human breast cancer cells. Methods: Constructing recombinant expression v...Objective: To study the effects of recombinant expression vector containing human breast cancer DF3 promotor and diphtheria toxin A fragment on human breast cancer cells. Methods: Constructing recombinant expression vector PGL3-DF3-DTA and transfecting it into human breast cancer cells of DF3 positive and negative. By means of RT-PCR to measure the expression of DTA in human breast cancer cells. MTT color-imetry was used to examine the effect of PGL3-DF3-DTA on growth of human breast cancer cells. By experiment on nude mice to observe the killing effect of PGL3-DF3-DTA on human breast cancer cells. Results: Recombinant expression vector PGL3-DF3-DTA was highly expressed in human breast cancer cell line of DF3 positive, and it could kill the human breast cancer cells not only in vitro but also in vivo. Conclusion: Recombinant expression vector PGL3-DF3-DTA could produce specific killing effect on human breast cancer cell line of DF3 positive.展开更多
[ Objectives] As a traditional inoculation method of rice sheath blight, rice relative lesion height method needs rice grow to late tillering or heading stage and then inoculate in vivo, which is time-consuming and is...[ Objectives] As a traditional inoculation method of rice sheath blight, rice relative lesion height method needs rice grow to late tillering or heading stage and then inoculate in vivo, which is time-consuming and is difficult to control the testing conditions, so it is urgent to search a better alternative method. [ Methods] With rice relative lesion height method （ in vivo inoculation） as the control, the pathogenicity and crude toxin activity of Rhizoctonia solani were determined by rice detached leaf sheath method and rice detached leaf method, to compare the correlation of in vivo and in vitro inoculation. [Results] Rice detached leaf method and rice detached leaf sheath method had significantly positive correlation with rice relative lesion height method, and the determination results of rice detached leaf method and rice detached leaf sheath method could reflect the pathogenicity and crude toxin activity of R. solani accurately. [ Conclusions] Rice detached leaf method and rice detached leaf sheath method are easy to operate and control testing conditions, and could be used as alternative methods to determine pathogenicity and etude toxin activity of R. solani.展开更多
Dear Editor, We want to describe the surgical outcome of a patient with residual esotropia due to sixth nerve palsy with re-resection of the lateral rectus combined with botulinum toxin injection to previously recesse...Dear Editor, We want to describe the surgical outcome of a patient with residual esotropia due to sixth nerve palsy with re-resection of the lateral rectus combined with botulinum toxin injection to previously recessed ipsilateral medial rectus.Sixth nerve palsy may be vasculopathic, traumatic, neoplastic,展开更多
Objective: To identify the relationship between T-2 toxin and Kashin-Beck disease (KBD),the effects of T-2 toxin on aggrecan metabolism in human chondrocytes and cartilage were investigated in vitro. Methods: Chondroc...Objective: To identify the relationship between T-2 toxin and Kashin-Beck disease (KBD),the effects of T-2 toxin on aggrecan metabolism in human chondrocytes and cartilage were investigated in vitro. Methods: Chondrocytes were isolated from human articular cartilage and cultured in vitro. Hyaluronic acid (HA),soluble CD44 (sCD44),IL-1β and TNF-α levels in super-natants were measured by enzyme-linked immunosorbent assay (ELISA). CD44 content in chondrocyte membrane was deter-mined by flow cytometry (FCM). CD44,hyaluronic acid synthetase-2 (HAS-2) and aggrecanases mRNA levels in chondrocytes were determined using reverse transcription polymerase chain reaction (RT-PCR). Immunocytochemical method was used to investigate expressions of BC-13,3-B-3(-) and 2-B-6 epitopes in the cartilage reconstructed in vitro. Results: T-2 toxin inhibited CD44,HAS-2,and aggrecan mRNA expressions,but promoted aggrecanase-2 mRNA expression. Meanwhile,CD44 expression was found to be the lowest in the chondrocytes cultured with T-2 toxin and the highest in control plus selenium group. In addition,ELISA results indicated that there were higher sCD44,IL-1β and TNF-α levels in T-2 toxin group. Similarly,higher HA levels were also observed in T-2 toxin group using radioimmunoprecipitation assay (RIPA). Furthermore,using monoclonal antibodies BC-13,3-B-3 and 2-B-6,strong positive immunostaining was found in the reconstructed cartilage cultured with T-2 toxin,whereas no positive staining or very weak staining was observed in the cartilage cultured without T-2 toxin. Selenium could partly inhibit the effects of T-2 toxin above. Conclusion: T-2 toxin could inhibit aggrecan synthesis,promote aggrecanases and pro-inflammatory cytokines production,and consequently induce aggrecan degradation in chondrocytes. These will perturb metabolism balance between aggrecan synthesis and degradation in cartilage,inducing aggrecan loss in the end,which may be the initiation of the cartilage degradation.展开更多
No recommended guidelines currently exist for the therapeutic concentration or dose of botulinum toxin type A （BTXA） injected into the muscle to treat limb spasticity. Therefore, in this randomized controlled trial,...No recommended guidelines currently exist for the therapeutic concentration or dose of botulinum toxin type A （BTXA） injected into the muscle to treat limb spasticity. Therefore, in this randomized controlled trial, we explored the safety and efficacy of two concentrations and two doses of BTXA in the treatment of spastic toot after stroke to optimize this treatment in these patients. Eligible patients （n = 104） were randomized into four groups. The triceps surae and tibialis posterior on the affected side were injected with BTXA at one of two doses （200 U or 400 U） and two concentrations （50 U/mL or 100 U/mL）. 2he following assessments were conducted before as well as 4 days and 1, 2, 4, and 12 weeks after treatment： spasticity, assessed using the modified Ashworth scale; basic functional mobility, assessed using a timed up and go test; pace, assessed using a 10-meter timed walking test; and the ability to walk, assessed using Holden＇s graded scale and a visual analog scale. The reported results are based on the 89 patients that completed the study. We found significant differences for the two doses and concentrations of BTXA to improve the ability of patients to walk independently, with the high-dose/low-concentration combination providing the best effect. Onset and duration of the ameliorating effects of BTXA were 4-7 days and 12 weeks, respectively. Thus, BTXA effectively treated foot spasms after stroke at an optimal dose of 400 U and concentration of 50 U/mL.展开更多
Twelve healthy rats were divided into the T-2 toxin group receiving gavage of 1 mg/kg T-2 toxin and the control group receiving gavage of normal saline. Total relative concentrations of T-2 toxin and HT-2 toxin in the...Twelve healthy rats were divided into the T-2 toxin group receiving gavage of 1 mg/kg T-2 toxin and the control group receiving gavage of normal saline. Total relative concentrations of T-2 toxin and HT-2 toxin in the skeletal system（thighbone, knee joints, and costal cartilage） were significantly higher than those in the heart, liver, and kidneys（P 〈 0.05）. The relative concentrations of T-2 toxin and HT-2 toxin in the skeletal system（thighbone and costal cartilage） were also significantly higher than those in the heart, liver, and kidneys. The rats administered T-2 toxin showed rapid metabolism compared with that in rats administered HT-2 toxin, and the metabolic conversion rates in the different tissues were 68.20%-90.70%.展开更多
BACKGROUND Lateral internal sphincterotomy is still the approach of choice for the treatment of chronic anal fissure(CAF)with internal anal sphincter(IAS)hypertonia,but it is burdened by high-risk postoperative faecal...BACKGROUND Lateral internal sphincterotomy is still the approach of choice for the treatment of chronic anal fissure(CAF)with internal anal sphincter(IAS)hypertonia,but it is burdened by high-risk postoperative faecal incontinence(FI).Sphincter saving procedures have recently been reconsidered as treatments to overcome this risk.The most employed procedure is fissurectomy with anoplasty,eventually associated with pharmacological sphincterotomy.AIM To evaluate whether fissurectomy and anoplasty with botulinum toxin injection improves the results of fissurectomy and anoplasty alone.METHODS We conducted a case-control study involving 30 male patients affected by CAF with hypertonic IAS who underwent fissurectomy and anoplasty with V-Y cutaneous flap advancement.The patients were divided into two groups:Those in group I underwent surgery alone,and those in group II underwent surgery and a botulinum toxin injection directly into the IAS.They were followed up for at least 2 years.The goals were to achieve complete healing of the patient and to assess the FI and recurrence rate along with manometry parameters.RESULTS The intensity and duration of post-defecatory pain decreased significantly in both groups of patients starting with the first defecation,and this reduction was higher in group II.Forty days after surgery,we achieved complete wound healing in all the patients in group II but only in 80%of the patients in group I(P<0.032).We recorded 2 cases of recurrence,one in each group,and both healed with conservative therapy.We recorded one temporary and low-grade postoperative case of“de novo”FI.Manometry parameters reverted to the normal range earlier for group II patients.CONCLUSION The injection of botulinum toxin A in association with fissurectomy and anoplasty with a V-Y advancement flap improves the results of surgery alone in patients affected by CAF with IAS hypertonia.展开更多
Objective To investigate the effect on the structure of reestablished cartilage in vitro and CD44 expression on chondrocytes and compare the inducing effect on the reestablished cartilage in vitro between cor...Objective To investigate the effect on the structure of reestablished cartilage in vitro and CD44 expression on chondrocytes and compare the inducing effect on the reestablished cartilage in vitro between cortical bone matrix gelatin and cancellous bone matrix gelatin. Methods To plant human fetal chondrocytes on the BMG, the damage of the cultured chondrocytes was observed by the optical microscope (HE staining). The immunohistochemistry of CD44 was quantitative analysis by the image collection and analysis system. Results With the increasing concentration of T 2 toxin, the damage of chondroytes was more and more evident and CD44 expression was lowered. After adding selenium, the damage was relieved and CD44 expression increased. The density of chondrocytes on the cortical bone matrix gelatin was much higher than that on the cancellous bone matrix gelatin. Conclusion T 2 toxin can lower the CD44 expression on the chondrocytes and adding selenium can relieve the damage caused by T 2toxin and increased CD44 expression. The inducing effect on reestablished cartilage in vitro of cortical bone matrix gelatin was much higher than that of cancellous bone matrix gelatin.展开更多
Objective To investigate chondrocyte apoptosis and the expression of biochemical markers associated with apoptosis in Kashin-Beck disease（KBD） and in an established T-2 toxin-and selenium（Se） deficiency-induced ra...Objective To investigate chondrocyte apoptosis and the expression of biochemical markers associated with apoptosis in Kashin-Beck disease（KBD） and in an established T-2 toxin-and selenium（Se） deficiency-induced rat model. Methods Cartilages were collected from the hand phalanges of five patients with KBD and five healthy children. Sprague-Dawley rats were administered a selenium-deficient diet for 4 weeks prior to T-2 toxin exposure. The apoptotic chondrocytes were observed by terminal deoxynucleotidyl transferase d UTP nick end labeling staining. Caspase-3, p53, Bcl-2, and Bax proteins in the cartilages were visualized by immunohistochemistry, their protein levels were determined by Western blotting, and m RNA levels were determined by real-time reverse transcription polymerase chain reaction. Results Increased chondrocyte apoptosis was observed in the cartilages of children with KBD. Increased apoptotic and caspase-3-stained cells were observed in the cartilages of rats fed with normal and Se-deficient diets plus T-2 toxin exposure compared to those in rats fed with normal and Se-deficient diets. Caspase-3, p53, and Bax proteins and m RNA levels were higher, whereas Bcl-2 levels were lower in rats fed with normal or Se-deficiency diets supplemented with T-2 toxin than the corresponding levels in rats fed with normal diet. Conclusion T-2 toxin under a selenium-deficient nutritional status induces chondrocyte death, which emphasizes the role of chondrocyte apoptosis in cartilage damage and progression of KBD.展开更多
Benign prostatic hyperplasia(BPH)is a clinical condition where lower urinary tract symptoms are caused by both a physically obstructing prostate as well as tight smooth muscles around the bladder outlet.Treatment of t...Benign prostatic hyperplasia(BPH)is a clinical condition where lower urinary tract symptoms are caused by both a physically obstructing prostate as well as tight smooth muscles around the bladder outlet.Treatment of this condition with botulinum toxin has been used since 2003,but this interest has somewhat died down after two large randomized controlled trials(RCTs)showing equivalence of results between their treatment and placebo arms.However,with review of animal studies and unexplained exaggerated effect of the placebo arms of the two RCTs,together with recent data of sustained benefits after 18 months of treatment,the place of botulinum toxin in the BPH field is probably still present.展开更多
AIM： To investigate the selective cytotoxic effect of constructed hybrid protein on cells expressing granulocyte macrophage colony stimulating factor （GM-CSF） receptor. METHODS： HepG2 （human hepatoma） and LS174T...AIM： To investigate the selective cytotoxic effect of constructed hybrid protein on cells expressing granulocyte macrophage colony stimulating factor （GM-CSF） receptor. METHODS： HepG2 （human hepatoma） and LS174T （colon carcinoma） were used in this study. The fused gene was induced with 0.02% of arabinose for 4 h and the expressed protein was detected by Western blotting. The chimeric protein expressed in E..coli was checked for its cytotoxic activity on these cells and apoptosis was measured by comet assay and nudear staining. RESULTS： The chimeric protein was found to be cytotoxic to the colon cancer cell line expressing GM-CSFRs, but not to HepG2 lacking these receptors. Maximum activity was observed at the concentration of 40 ng/mL after 24 h incubation. The IC50 was 20 ± 3.5 ng/mL. CONCLUSION： Selective cytotoxic effect of the hybrid protein on the colon cancer cell line expressing GMCSF receptors （GM-CSFRs） receptor and apoptosis can be observed in this cell line. The hybrid protein can be considered as a therapeutic agent.展开更多
AIM: To report the surgical outcomes of correcting large angle intermittent exotropia in adult patients by bilateral lateral rectus muscle recession with intraoperative use of botulinum toxin and to compare the result...AIM: To report the surgical outcomes of correcting large angle intermittent exotropia in adult patients by bilateral lateral rectus muscle recession with intraoperative use of botulinum toxin and to compare the results with those of bilateral lateral rectus muscle recession and unilateral medial rectus resection. METHODS: The medical records of patients who underwent surgical correction of large angle intermittent exotropia [exotropia >50 prism dioptre(PD)] were retrospectively reviewed. Two groups of patients were identified;Group Ⅰ(21 patients) had bilateral lateral recti recession augmented with intraoperative botulinum toxin A(BTA) injection into the recessed muscles and group Ⅱ(30 patients) were treated by bilateral lateral recti recession with unilateral medial rectus muscle resection. Preoperative data were extracted for age, gender, refraction, type of exotropia, angle of stereopsis and angle of deviation. The main outcome measures were the postoperative angle of deviation and stereoacuity angle by Titmus test measured at the end of one year of postoperative follow up. RESULTS: By the end of the first postoperative year, 10 patients in group Ⅰ(47.6%) and 20 patients in group Ⅱ(66.7%) achieved esotropia/esophoria <5 PD or exotropia/exophoria <10 PD. The difference in surgical success rate was not statistically significant(P=0.1) but there was a statistically significant higher rate of undercorrection in group Ⅰ(P=0.03). On the other hand, 3 patients in group Ⅰ(14.3%) and 5 patients in group Ⅱ(16.7%) had improved stereopsis;this difference in the sensory outcome was not statistically significant(P=0.8). In the BTA augmented surgery group, good stereoacuity and smaller preoperative angle of deviation were associated with significantly higher surgical success rate(P=0.004, 0.01 respectively). CONCLUSION: BTA augmented bilateral lateral recti recession is associated with higher rate of undercorrection as compared to bilateral lateral recti recession with unilateral medial rectus resection in the correction of large angle intermittent exotropia. The surgical success rate in BTA augmented surgery group is observed to be higher in patients with preoperative smaller angle of deviation and in patients with good stereoacuity.展开更多
The purpose of this experimental study was to evaluate and record the effects of T-2 toxicity alone and in association with IBV infection on haematobiochemical parameters. A total of 128 one-week-old chicks were divid...The purpose of this experimental study was to evaluate and record the effects of T-2 toxicity alone and in association with IBV infection on haematobiochemical parameters. A total of 128 one-week-old chicks were divided into four groups of 32 birds each and were treated respectively with T-2 toxin alone, IBV alone, T-2 toxin and co-infected with IBV, and no treatment (control) for a period of 6 weeks. Haematologically, the birds treated with T-2 toxin developed anaemia as indicated by significant decrease in haemoglobin levels, total erythrocyte counts and packed cell volume values;leucopenia, lymphocytopenia heterophilia and thrombocytopenia. The IBV infected birds exhibited lymphocytophilia and heteropoenia;the degrees of severity of leucopenia, lymphocytopenia heterophilia and thrombocytopenia were more pronounced in T-2+IBV groups. The serum biochemistry revealed hypoproteinemia and hypoalbuminemia in all the treated groups consistently. Besides, hypoglobulinemia and increased levels of alanine aminotransferase in T-2+IBV, and increased levels of alkaline phosphatase in toxin group alone were recorded. The changes in biochemical parameters were more in magnitude in the combination treatment group and their severity increased with duration of treatment. It was concluded that T-2 toxin made the birds more susceptible to IBV infection.展开更多
Cholera is a well-known gastrointestinal infection.The cholera toxin is an important pathological substance in pathogenesis of cholera diarrhea.Cholera toxin is composed of catalytic A1 subunit,an A2 linker,and a homo...Cholera is a well-known gastrointestinal infection.The cholera toxin is an important pathological substance in pathogenesis of cholera diarrhea.Cholera toxin is composed of catalytic A1 subunit,an A2 linker,and a homopentameric cell-binding B subunit.In enterocyte,cholera toxin will attach to GM1 ganglioside receptors on the apical membrane and causes retrograde vesicular trafficking to endoplasmic reticulum.At endoplasmic reticulum,cholera toxin A1 is released from the rest of the toxin into cytoplasm.The cholera toxin A1 interacts will catalyze ADP ribosylation of subunits of stimulatory G protein resulting a persistent activation of adenylate cyclase and an elevation of intracellular c AMP which further result in diarrhea.The single alanine substitutional mutation can result in the reduction of the interaction activity between cholera toxin A1 and stimulatory G protein.In this study,the four well-known mutations,H55,R67,L71,S78,or D109,of cholera toxin A1 is focused.The author hereby calculates for the reaction energy for the reaction between cholera toxin A1 and stimulatory G protein in na¨?ve case and mutated case.To calculate,the standard bonding energy calculation technique in mutation analysis was used.It can be seen that aberrant in reaction energy in each studied mutation is different and can imply the different effect on activity with stimulatory G protein.展开更多
基金Supported by the Special Funds of Jiangsu Provincial Key Research and Development Projects,No.BE2019612Scientific Research Project Cooperated by Lanzhou Biotechnology Development Co.,Ltd.+3 种基金the Key R&D Program of Jiangsu Science and Technology Project,No.BE2022049 and No.BE2022049-1National Natural Science Foundation of China,No.82171249Nanjing Rehabilitation Medicine Center ProjectJiangsu Provincial Health Commission Special Fund for Aging and Health.
文摘BACKGROUND The previous studies have primarily focused on the influence of botulinum toxin A(BoNT-A)injection on emotions during the period of peak motor symptom improvement in blepharospasm patients,based on facial feedback hypothesis.AIM To evaluate the sustained anxiolytic and antidepressant effects of BoNT-A in blepharospasm patients beyond motor symptom control.METHODS We recruited benign essential blepharospasm patients with BoNT-A treatment and collected their data to compare scale scores of Jankovic Rating Scale,Blepharospasm Disability Index,Self-rating Anxiety Scale(SAS),Self-rating Depression Scale(SDS),Hamilton Anxiety Scale and Hamilton Depression Scale between pretreatment(baseline)and pre-reinjection(treatment),to further assess the effects of repeated treatments with BoNT by using sub-group analyses in the certain special states.RESULTS A total of 21 eligible blepharospasm patients were with the mean age of 58.4 years and a male-to-female ratio of 1:6.Significantly decreases in the subscale scores of SDS and SAS,including SDS well-being index,decreased capacity and hard to decide,SAS inability to sit still and headache were showed at post-a single BoNT-A injection when scale scores of Jankovic Rating Scale and Blepharospasm Disability Index were matched between baseline and posttreatment.With each additional BoNT-A injection,the odds ratio of patients with the moderate depressive symptoms decreased by 92.6%.Moreover,BoNT treatment remained a decrease in the subscale scores of SDS and SAS in patients with repeated injections.CONCLUSION This study is to demonstrate that repeated BoNT-A injection have a long-lasting relief for anxiety and depressive symptoms in blepharospasm even after its motor symptom-modulating effects have diminished.
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.
基金grants from the National Natural Science Foundation of China （Nos. 30973336 and 81100762）.
文摘Botulinum toxin A （BTXA） has been used in several clinical trials to treat excessive glandular secretion; however, the precise mechanism of its action on the secretory function of salivary gland has not been fully elucidated. In this study, we aimed to investigate the effect of BTXA on secretion of submandibular gland in rabbits and to identify its mechanism of action on the secretory function of salivary gland. At 12 weeks after injection with 5 units of BTXA, we found a significant decrease in the saliva flow from submandibular glands, while the salivary amylase concentration increased. Morphological analysis revealed reduction in the size of acinar cells with intracellular accumulation of secretory granules that coalesced to form a large ovoid structure. Expression of M3-muscarinic acetylcholine receptor （M3 receptor） and aquaporin-5 （AQP5） mRNA decreased after BTXA treatment, and distribution of AQP5 in the apical membrane was reduced at 1, 2 and 4 weeks after BTXA injection. Furthermore, BTXA injection was found to induce apoptosis of acini. These results indicate that BTXA decreases the fluid secretion of submandibular glands and increases the concentration of amylase in saliva. Decreased expression of M3 receptor and AQP5, inhibition of AQP5 translocation, and cell apoptosis might involve in BTXA-reduced fluid secretion of submandibular lands.
基金Supported by PRONEX CNPq/FUNCAP,No.PR2-0101-00060.01.00/15Sao Paulo Research Foundation(FAPESP),No.2014/25927-2 and No.2018/07862-1.
文摘Clostridioides difficile(C.difficile)is the most common pathogen causing health care-associated infections.C.difficile TcdA and TcdB have been shown to activate enteric neurons;however,what population of these cells is more profoundly influenced and the mechanism underlying these effects remain unknown.AIM To characterize a specific population of TcdA-affected myenteric neurons and investigate the role of the P2X7 receptor in TcdA-induced ileal inflammation,cell death,and the changes in the enteric nervous system in mice.METHODS Swiss mice were used to model TcdA-induced ileitis in ileal loops exposed to TcdA(50μg/Loop)for 4 h.To investigate the role of the P2X7 receptor,Brilliant Blue G(50 mg/kg,i.p.),which is a nonspecific P2X7 receptor antagonist,or A438079(0.7μg/mouse,i.p.),which is a competitive P2X7 receptor antagonist,were injected one hour prior to TcdA challenge.Ileal samples were collected to analyze the expression of the P2X7 receptor(by quantitative real-time polymerase chain reaction and immunohistochemistry),the population of myenteric enteric neurons(immunofluorescence),histological damage,intestinal inflammation,cell death(terminal deoxynucleotidyltransferasemediated dUTP-biotin nick end labeling),neuronal loss,and S100B synthesis(immunohistochemistry).RESULTS TcdA upregulated(P<0.05)the expression of the P2X7 receptor gene in the ileal tissues,increasing the level of this receptor in myenteric neurons compared to that in control mice.Comparison with the control mice indicated that TcdA promoted(P<0.05)the loss of myenteric calretinin+(Calr)and choline acetyltransferase+neurons and increased the number of nitrergic+and Calr+neurons expressing the P2X7 receptor.Blockade of the P2X7 receptor decreased TcdAinduced intestinal damage,cytokine release[interleukin(IL)-1β,IL-6,IL-8,and tumor necrosis factor-α],cell death,enteric neuron loss,and S100B synthesis in the mouse ileum.CONCLUSION Our findings demonstrated that TcdA induced the upregulation of the P2X7 receptor,which promoted enteric neuron loss,S100B synthesis,tissue damage,inflammation,and cell death in the mouse ileum.These findings contribute to the future directions in understanding the mechanism involved in intestinal dysfunction reported in patients after C.difficile infection.
文摘More than 70% children with cerebral palsy belong to the spastic one, and the increased muscular tension results in motor dysfunction and posture abnormality. OBJECTIVE： To observe the assistant effect of the local injection of BTX-A at multiple points in the rehabilitative treatment of spastic cerebral palsy. DESIGN： A comparative observation on the clinical efficacy. SETTINGS： Rehabilitation Center, Loufeng Hospital, Suzhou Industrial Park; Gansu Rehabilitation Center Hospital. PARTICIPANTS： Sixty-nine children with cerebral palsy were selected from the outpatients and inpatients who accepted rehabilitative treatments in the Cerebral Palsy Treatment Center of Gansu Rehabilitation Center Hospital from April 2003 and October 2004. Inclusive criteria： ①Having high risk factors for brain injury before birth and within 1 month after birth, mainly manifested as central motor disorder and posture abnormality; ② Accompanied by increase of muscular tension in both lower limbs, appearing as tiptoes and scissors gaits while in standing position or walking; ③ Without fixed contracture of lower limb; ④ Had never been operated for lower limbs; ⑤ Had never been injected with BTX-A; ⑥ Clearly diagnosed to have spastic palsy. The enrolled children were not screened by disease conditions, course, age, etc., and informed consents were obtained from the parents of all the children. The children whose parents agreed to accept BTX-A treatment were taken as BTX-A treated group （n =45）, and the others as control group （n = 24）. METHODS： All the children accepted regular rehabilitative training after admission, 6 times a weeks, besides, those in the BTX-A treated group were given local injection of BTX-A at multiple points of target muscles, including bilateral adductor longus muscles, pectineal muscles, gastrocnemius muscles and soleus muscles. BTX-A was diluted with saline （5 U BTX-A in 0.1 mL）, 3 - 4 U/kg for each piece of muscle. The number of injected sites depended on the size of target muscle, and no more than 0.5 mL for each site. The injection should be followed by manual massage for 1 - 2 minutes, and electromuscular stimulation for 20 minutes, which were continued for 3 days. They participated in the comprehensive rehabilitative training and treatment at 24 hours after injection. MAIN OUTCOME MEASURES： The comprehensive abilities of cerebral palsy were evaluated, the adductor angle and forced area on soles were measured before treatment and at 3 and 6 months after treatment. RESULTS： All the 69 children with spastic cerebral palsy were involved in the analysis of results. ① Efficacy in the BTX-A treated group： BTX-A began to take effect at 48 hours after injection, and the maximal effect was observed in all the cases on the 6th day; 2 weeks later, the scissors gaits and hip adduction were obviously improved in 39 and 11 cases, respectively, and tiptoes gaits were improved in 22 cases; 2 months later, tiptoes gaits were improved in 43 cases. ② Efficacy in the control group： Two months later, certain improvements of scissors gaits were observed in 2 children with mild cerebral palsy; the scissors gaits and tiptoes were obviously improved in 6 cases of moderate cerebral palsy and 3 cases of mild one after 3 months, and there were changes of the parameters after 6 months in 1, 10 and 5 cases of severe, moderate and mild cerebral palsy, respectively. ③ Improvement of adductor angle before and after treatment in both groups： The muscular tension was evaluated according to Komam＇s method. There was no obvious difference in the adductor angle between the two groups before treatment （P 〉 0.05）. The adductor angle had very significant difference （P 〈 0.01） and significant difference （P 〈 0.05） between the two groups at 3 and 6 months after treatment. ④ Changes of forced area on soles before and after treatment in bothgroups： The forced area on soles was assessed referred to the method of foot-print analysis. There was no obvious difference in the forced area on soles between the two groups before treatment （P 〉 0.05）. The forced area on soles had very significant difference （P 〈 0.01） and significant difference （P 〈 0.05） between the two groups at 3 and 6 months after treatment. CONCLUSION： BTX-A local injection is an important assistant therapeutic method for treating spastic cerebral palsy. For the patients with moderate and severe cerebral palsy, BTX-A local injection should be combined with rehabilitative training to obviously shorten the course and improve efficacy.
基金supported by the National Basic Research Program of China(973 Program No.2011CB944203, No.2011CB944202)the National Science Supporting Plan of China(No.2011BAD19B03)
文摘Diphtheria toxin A （DTA）, a segment of the diphtheria toxin （tox）, inhibits protein synthesis in cells. When released from a cell, DTA is nontoxic and cannot enter other cells independently without the help of diphtheria toxin B. In this study, we artificially synthesized the DTA gene sequence and cloned it into pEGFP-N1 to generate the recombinant vector pEGFP-N1-DTA. This recombinant vector was then transfected into 293T cells to observe the effect of DTA protein expression on enhanced green fluorescent protein （EGFP） protein expression and the proliferation of 293T cells. After 48 h, high levels of EGFP expression were seen in control pEGFP-Nl-transfected cells, whereas very low levels were seen in cells transfected with pEGFP-N1-DTA. Reverse transcription polymerase chain reaction confirmed the expression of the DTA gene in cells transfected with pEGFP-N^-DTA. Further, the 3-（4,5-dimethylthiazol-2-yl）-2,5-diphenyltetrazolium bromide （M-I-I-） assay revealed a significant difference in cell proliferation between the control group and the pEGFP-N1-DTA-transfected group. Using the expression of EGFP expression as an indicator, this study revealed that DTA expression can inhibit intracellular protein synthesis and cell proliferation.
基金Health Department Scientific Research Foundation of Hubei province (No. NX200501)
文摘Objective: To study the effects of recombinant expression vector containing human breast cancer DF3 promotor and diphtheria toxin A fragment on human breast cancer cells. Methods: Constructing recombinant expression vector PGL3-DF3-DTA and transfecting it into human breast cancer cells of DF3 positive and negative. By means of RT-PCR to measure the expression of DTA in human breast cancer cells. MTT color-imetry was used to examine the effect of PGL3-DF3-DTA on growth of human breast cancer cells. By experiment on nude mice to observe the killing effect of PGL3-DF3-DTA on human breast cancer cells. Results: Recombinant expression vector PGL3-DF3-DTA was highly expressed in human breast cancer cell line of DF3 positive, and it could kill the human breast cancer cells not only in vitro but also in vivo. Conclusion: Recombinant expression vector PGL3-DF3-DTA could produce specific killing effect on human breast cancer cell line of DF3 positive.
基金Supported by National Natural Science Foundation of China(31160352,31360423)Science and Technology Innovation Team Support Plan for Colleges and Universities in Yunnan Province(YJK[2014]22)
文摘[ Objectives] As a traditional inoculation method of rice sheath blight, rice relative lesion height method needs rice grow to late tillering or heading stage and then inoculate in vivo, which is time-consuming and is difficult to control the testing conditions, so it is urgent to search a better alternative method. [ Methods] With rice relative lesion height method （ in vivo inoculation） as the control, the pathogenicity and crude toxin activity of Rhizoctonia solani were determined by rice detached leaf sheath method and rice detached leaf method, to compare the correlation of in vivo and in vitro inoculation. [Results] Rice detached leaf method and rice detached leaf sheath method had significantly positive correlation with rice relative lesion height method, and the determination results of rice detached leaf method and rice detached leaf sheath method could reflect the pathogenicity and crude toxin activity of R. solani accurately. [ Conclusions] Rice detached leaf method and rice detached leaf sheath method are easy to operate and control testing conditions, and could be used as alternative methods to determine pathogenicity and etude toxin activity of R. solani.
文摘Dear Editor, We want to describe the surgical outcome of a patient with residual esotropia due to sixth nerve palsy with re-resection of the lateral rectus combined with botulinum toxin injection to previously recessed ipsilateral medial rectus.Sixth nerve palsy may be vasculopathic, traumatic, neoplastic,
基金Project supported by the National Natural Science Foundation of China (Nos. 30471499 and 30170831)the Ministry of Education of China (No.Key 03152)the Science Foundation of Shaanxi Province of China (No.2004KW-20)
文摘Objective: To identify the relationship between T-2 toxin and Kashin-Beck disease (KBD),the effects of T-2 toxin on aggrecan metabolism in human chondrocytes and cartilage were investigated in vitro. Methods: Chondrocytes were isolated from human articular cartilage and cultured in vitro. Hyaluronic acid (HA),soluble CD44 (sCD44),IL-1β and TNF-α levels in super-natants were measured by enzyme-linked immunosorbent assay (ELISA). CD44 content in chondrocyte membrane was deter-mined by flow cytometry (FCM). CD44,hyaluronic acid synthetase-2 (HAS-2) and aggrecanases mRNA levels in chondrocytes were determined using reverse transcription polymerase chain reaction (RT-PCR). Immunocytochemical method was used to investigate expressions of BC-13,3-B-3(-) and 2-B-6 epitopes in the cartilage reconstructed in vitro. Results: T-2 toxin inhibited CD44,HAS-2,and aggrecan mRNA expressions,but promoted aggrecanase-2 mRNA expression. Meanwhile,CD44 expression was found to be the lowest in the chondrocytes cultured with T-2 toxin and the highest in control plus selenium group. In addition,ELISA results indicated that there were higher sCD44,IL-1β and TNF-α levels in T-2 toxin group. Similarly,higher HA levels were also observed in T-2 toxin group using radioimmunoprecipitation assay (RIPA). Furthermore,using monoclonal antibodies BC-13,3-B-3 and 2-B-6,strong positive immunostaining was found in the reconstructed cartilage cultured with T-2 toxin,whereas no positive staining or very weak staining was observed in the cartilage cultured without T-2 toxin. Selenium could partly inhibit the effects of T-2 toxin above. Conclusion: T-2 toxin could inhibit aggrecan synthesis,promote aggrecanases and pro-inflammatory cytokines production,and consequently induce aggrecan degradation in chondrocytes. These will perturb metabolism balance between aggrecan synthesis and degradation in cartilage,inducing aggrecan loss in the end,which may be the initiation of the cartilage degradation.
基金supported by a grant from the Shandong Science and Technology Development Plan Project in China,No.2012YD18031
文摘No recommended guidelines currently exist for the therapeutic concentration or dose of botulinum toxin type A （BTXA） injected into the muscle to treat limb spasticity. Therefore, in this randomized controlled trial, we explored the safety and efficacy of two concentrations and two doses of BTXA in the treatment of spastic toot after stroke to optimize this treatment in these patients. Eligible patients （n = 104） were randomized into four groups. The triceps surae and tibialis posterior on the affected side were injected with BTXA at one of two doses （200 U or 400 U） and two concentrations （50 U/mL or 100 U/mL）. 2he following assessments were conducted before as well as 4 days and 1, 2, 4, and 12 weeks after treatment： spasticity, assessed using the modified Ashworth scale; basic functional mobility, assessed using a timed up and go test; pace, assessed using a 10-meter timed walking test; and the ability to walk, assessed using Holden＇s graded scale and a visual analog scale. The reported results are based on the 89 patients that completed the study. We found significant differences for the two doses and concentrations of BTXA to improve the ability of patients to walk independently, with the high-dose/low-concentration combination providing the best effect. Onset and duration of the ameliorating effects of BTXA were 4-7 days and 12 weeks, respectively. Thus, BTXA effectively treated foot spasms after stroke at an optimal dose of 400 U and concentration of 50 U/mL.
基金partially supported by National Natural Scientific Foundation of China[81620108026,81302393]
文摘Twelve healthy rats were divided into the T-2 toxin group receiving gavage of 1 mg/kg T-2 toxin and the control group receiving gavage of normal saline. Total relative concentrations of T-2 toxin and HT-2 toxin in the skeletal system（thighbone, knee joints, and costal cartilage） were significantly higher than those in the heart, liver, and kidneys（P 〈 0.05）. The relative concentrations of T-2 toxin and HT-2 toxin in the skeletal system（thighbone and costal cartilage） were also significantly higher than those in the heart, liver, and kidneys. The rats administered T-2 toxin showed rapid metabolism compared with that in rats administered HT-2 toxin, and the metabolic conversion rates in the different tissues were 68.20%-90.70%.
文摘BACKGROUND Lateral internal sphincterotomy is still the approach of choice for the treatment of chronic anal fissure(CAF)with internal anal sphincter(IAS)hypertonia,but it is burdened by high-risk postoperative faecal incontinence(FI).Sphincter saving procedures have recently been reconsidered as treatments to overcome this risk.The most employed procedure is fissurectomy with anoplasty,eventually associated with pharmacological sphincterotomy.AIM To evaluate whether fissurectomy and anoplasty with botulinum toxin injection improves the results of fissurectomy and anoplasty alone.METHODS We conducted a case-control study involving 30 male patients affected by CAF with hypertonic IAS who underwent fissurectomy and anoplasty with V-Y cutaneous flap advancement.The patients were divided into two groups:Those in group I underwent surgery alone,and those in group II underwent surgery and a botulinum toxin injection directly into the IAS.They were followed up for at least 2 years.The goals were to achieve complete healing of the patient and to assess the FI and recurrence rate along with manometry parameters.RESULTS The intensity and duration of post-defecatory pain decreased significantly in both groups of patients starting with the first defecation,and this reduction was higher in group II.Forty days after surgery,we achieved complete wound healing in all the patients in group II but only in 80%of the patients in group I(P<0.032).We recorded 2 cases of recurrence,one in each group,and both healed with conservative therapy.We recorded one temporary and low-grade postoperative case of“de novo”FI.Manometry parameters reverted to the normal range earlier for group II patients.CONCLUSION The injection of botulinum toxin A in association with fissurectomy and anoplasty with a V-Y advancement flap improves the results of surgery alone in patients affected by CAF with IAS hypertonia.
文摘Objective To investigate the effect on the structure of reestablished cartilage in vitro and CD44 expression on chondrocytes and compare the inducing effect on the reestablished cartilage in vitro between cortical bone matrix gelatin and cancellous bone matrix gelatin. Methods To plant human fetal chondrocytes on the BMG, the damage of the cultured chondrocytes was observed by the optical microscope (HE staining). The immunohistochemistry of CD44 was quantitative analysis by the image collection and analysis system. Results With the increasing concentration of T 2 toxin, the damage of chondroytes was more and more evident and CD44 expression was lowered. After adding selenium, the damage was relieved and CD44 expression increased. The density of chondrocytes on the cortical bone matrix gelatin was much higher than that on the cancellous bone matrix gelatin. Conclusion T 2 toxin can lower the CD44 expression on the chondrocytes and adding selenium can relieve the damage caused by T 2toxin and increased CD44 expression. The inducing effect on reestablished cartilage in vitro of cortical bone matrix gelatin was much higher than that of cancellous bone matrix gelatin.
基金supported by the National Natural Science Foundation of China(No.81573102 and No.81273006)the Scientific Research Foundation for the Returned Overseas Chinese Scholars,State Education Ministry(11-01)
文摘Objective To investigate chondrocyte apoptosis and the expression of biochemical markers associated with apoptosis in Kashin-Beck disease（KBD） and in an established T-2 toxin-and selenium（Se） deficiency-induced rat model. Methods Cartilages were collected from the hand phalanges of five patients with KBD and five healthy children. Sprague-Dawley rats were administered a selenium-deficient diet for 4 weeks prior to T-2 toxin exposure. The apoptotic chondrocytes were observed by terminal deoxynucleotidyl transferase d UTP nick end labeling staining. Caspase-3, p53, Bcl-2, and Bax proteins in the cartilages were visualized by immunohistochemistry, their protein levels were determined by Western blotting, and m RNA levels were determined by real-time reverse transcription polymerase chain reaction. Results Increased chondrocyte apoptosis was observed in the cartilages of children with KBD. Increased apoptotic and caspase-3-stained cells were observed in the cartilages of rats fed with normal and Se-deficient diets plus T-2 toxin exposure compared to those in rats fed with normal and Se-deficient diets. Caspase-3, p53, and Bax proteins and m RNA levels were higher, whereas Bcl-2 levels were lower in rats fed with normal or Se-deficiency diets supplemented with T-2 toxin than the corresponding levels in rats fed with normal diet. Conclusion T-2 toxin under a selenium-deficient nutritional status induces chondrocyte death, which emphasizes the role of chondrocyte apoptosis in cartilage damage and progression of KBD.
文摘Benign prostatic hyperplasia(BPH)is a clinical condition where lower urinary tract symptoms are caused by both a physically obstructing prostate as well as tight smooth muscles around the bladder outlet.Treatment of this condition with botulinum toxin has been used since 2003,but this interest has somewhat died down after two large randomized controlled trials(RCTs)showing equivalence of results between their treatment and placebo arms.However,with review of animal studies and unexplained exaggerated effect of the placebo arms of the two RCTs,together with recent data of sustained benefits after 18 months of treatment,the place of botulinum toxin in the BPH field is probably still present.
文摘AIM： To investigate the selective cytotoxic effect of constructed hybrid protein on cells expressing granulocyte macrophage colony stimulating factor （GM-CSF） receptor. METHODS： HepG2 （human hepatoma） and LS174T （colon carcinoma） were used in this study. The fused gene was induced with 0.02% of arabinose for 4 h and the expressed protein was detected by Western blotting. The chimeric protein expressed in E..coli was checked for its cytotoxic activity on these cells and apoptosis was measured by comet assay and nudear staining. RESULTS： The chimeric protein was found to be cytotoxic to the colon cancer cell line expressing GM-CSFRs, but not to HepG2 lacking these receptors. Maximum activity was observed at the concentration of 40 ng/mL after 24 h incubation. The IC50 was 20 ± 3.5 ng/mL. CONCLUSION： Selective cytotoxic effect of the hybrid protein on the colon cancer cell line expressing GMCSF receptors （GM-CSFRs） receptor and apoptosis can be observed in this cell line. The hybrid protein can be considered as a therapeutic agent.
文摘AIM: To report the surgical outcomes of correcting large angle intermittent exotropia in adult patients by bilateral lateral rectus muscle recession with intraoperative use of botulinum toxin and to compare the results with those of bilateral lateral rectus muscle recession and unilateral medial rectus resection. METHODS: The medical records of patients who underwent surgical correction of large angle intermittent exotropia [exotropia >50 prism dioptre(PD)] were retrospectively reviewed. Two groups of patients were identified;Group Ⅰ(21 patients) had bilateral lateral recti recession augmented with intraoperative botulinum toxin A(BTA) injection into the recessed muscles and group Ⅱ(30 patients) were treated by bilateral lateral recti recession with unilateral medial rectus muscle resection. Preoperative data were extracted for age, gender, refraction, type of exotropia, angle of stereopsis and angle of deviation. The main outcome measures were the postoperative angle of deviation and stereoacuity angle by Titmus test measured at the end of one year of postoperative follow up. RESULTS: By the end of the first postoperative year, 10 patients in group Ⅰ(47.6%) and 20 patients in group Ⅱ(66.7%) achieved esotropia/esophoria <5 PD or exotropia/exophoria <10 PD. The difference in surgical success rate was not statistically significant(P=0.1) but there was a statistically significant higher rate of undercorrection in group Ⅰ(P=0.03). On the other hand, 3 patients in group Ⅰ(14.3%) and 5 patients in group Ⅱ(16.7%) had improved stereopsis;this difference in the sensory outcome was not statistically significant(P=0.8). In the BTA augmented surgery group, good stereoacuity and smaller preoperative angle of deviation were associated with significantly higher surgical success rate(P=0.004, 0.01 respectively). CONCLUSION: BTA augmented bilateral lateral recti recession is associated with higher rate of undercorrection as compared to bilateral lateral recti recession with unilateral medial rectus resection in the correction of large angle intermittent exotropia. The surgical success rate in BTA augmented surgery group is observed to be higher in patients with preoperative smaller angle of deviation and in patients with good stereoacuity.
文摘The purpose of this experimental study was to evaluate and record the effects of T-2 toxicity alone and in association with IBV infection on haematobiochemical parameters. A total of 128 one-week-old chicks were divided into four groups of 32 birds each and were treated respectively with T-2 toxin alone, IBV alone, T-2 toxin and co-infected with IBV, and no treatment (control) for a period of 6 weeks. Haematologically, the birds treated with T-2 toxin developed anaemia as indicated by significant decrease in haemoglobin levels, total erythrocyte counts and packed cell volume values;leucopenia, lymphocytopenia heterophilia and thrombocytopenia. The IBV infected birds exhibited lymphocytophilia and heteropoenia;the degrees of severity of leucopenia, lymphocytopenia heterophilia and thrombocytopenia were more pronounced in T-2+IBV groups. The serum biochemistry revealed hypoproteinemia and hypoalbuminemia in all the treated groups consistently. Besides, hypoglobulinemia and increased levels of alanine aminotransferase in T-2+IBV, and increased levels of alkaline phosphatase in toxin group alone were recorded. The changes in biochemical parameters were more in magnitude in the combination treatment group and their severity increased with duration of treatment. It was concluded that T-2 toxin made the birds more susceptible to IBV infection.
文摘Cholera is a well-known gastrointestinal infection.The cholera toxin is an important pathological substance in pathogenesis of cholera diarrhea.Cholera toxin is composed of catalytic A1 subunit,an A2 linker,and a homopentameric cell-binding B subunit.In enterocyte,cholera toxin will attach to GM1 ganglioside receptors on the apical membrane and causes retrograde vesicular trafficking to endoplasmic reticulum.At endoplasmic reticulum,cholera toxin A1 is released from the rest of the toxin into cytoplasm.The cholera toxin A1 interacts will catalyze ADP ribosylation of subunits of stimulatory G protein resulting a persistent activation of adenylate cyclase and an elevation of intracellular c AMP which further result in diarrhea.The single alanine substitutional mutation can result in the reduction of the interaction activity between cholera toxin A1 and stimulatory G protein.In this study,the four well-known mutations,H55,R67,L71,S78,or D109,of cholera toxin A1 is focused.The author hereby calculates for the reaction energy for the reaction between cholera toxin A1 and stimulatory G protein in na¨?ve case and mutated case.To calculate,the standard bonding energy calculation technique in mutation analysis was used.It can be seen that aberrant in reaction energy in each studied mutation is different and can imply the different effect on activity with stimulatory G protein.
