Objective:To investigate the effect of TSH inhibition therapy in the postoperative management of patients with differentiated thyroid cancer.Methods:Seventy patients diagnosed with differentiated thyroid cancer were s...Objective:To investigate the effect of TSH inhibition therapy in the postoperative management of patients with differentiated thyroid cancer.Methods:Seventy patients diagnosed with differentiated thyroid cancer were selected for the study.TSH inhibition therapy was administered to the research group,while thyroxine replacement therapy was provided to the control group during the postoperative management phase.This allowed for a comparative analysis between the two groups.Results:In comparison with the control group,the research group exhibited significant decreases in serum TSH,T3,and T4 levels after treatment,while FT4 and FT3 levels significantly increased(P<0.05).Additionally,significant decreases in Tg,VEGF,TSGF,CD44V6,and sIL-2R levels were observed in the research group after treatment(P<0.05).No significant differences were found in pre-treatment thyroid function between the two groups(P>0.05).Conclusion:The application of TSH inhibition therapy in the postoperative management of patients with differentiated thyroid cancer demonstrates promising outcomes.展开更多
Dysregulated Wnt signaling is associated with the pathogenesis of cancers, fibrosis, and vascular diseases. Inhibition of Wnt signaling has shown efficacy in various pre-clinical models of these disorders. One of the ...Dysregulated Wnt signaling is associated with the pathogenesis of cancers, fibrosis, and vascular diseases. Inhibition of Wnt signaling has shown efficacy in various pre-clinical models of these disorders. One of the key challenges in developing targeted anti-cancer drugs is to balance efficacy with on-target toxicity. Given the crucial role Wnts play in the differentiation of osteoblasts and osteoclasts, acute inhibition of Wnt signaling is likely to affect bone homeostasis. In this study, we evaluated the skeletal effect of small molecule inhibitor of an o-acyl transferase porcupine(PORCN) that prevents Wnt signaling by blocking the secretion of all Wnts. Micro-computed tomography and histomorphometric evaluation revealed that the bones of mice treated with two structurally distinct PORCN inhibitors LGK974 and ETC-1922159(ETC-159) had loss-of-bone volume and density within 4 weeks of exposure. This decreased bone mass was associated with a significant increase in adipocytes within the bone marrow. Notably,simultaneous administration of a clinically approved anti-resorptive, alendronate, a member of the bisphosphonate family,mitigated loss-of-bone mass seen upon ETC-159 treatment by regulating activity of osteoclasts and blocking accumulation of bone marrow adipocytes. Our results support the addition of bone protective agents when treating patients with PORCN inhibitors.Mitigation of bone toxicity can extend the therapeutic utility of Wnt pathway inhibitors.展开更多
Objective:To investigate the application value of thrombelastogram(TEG)in the detection of platelet inhibition rate for antiplatelet therapy for acute non-cardiogenic stroke.Methods:A total of 100 patients with ischem...Objective:To investigate the application value of thrombelastogram(TEG)in the detection of platelet inhibition rate for antiplatelet therapy for acute non-cardiogenic stroke.Methods:A total of 100 patients with ischemic non-cardiogenic stroke were selected for this study from September 2020 to October 2021.Patients were randomly divided into experimental group and control group,with 50 cases for each group.Before and after 1 week of antiplatelet drug treatment,the platelet inhibition rate in the experimental group was measured with arachidonic acid(AA)and adenosine diphosphate(ADP)by TEG;no platelet inhibition rates detection was conducted for the control group.The dose and type of drugs were adjusted for the experimental group according to the platelet functions and medication based on the clinical experience conducted for the control group.The neurological deficits of the discharged patients were scored with NIHSS score,mRS score,stroke recurrence,hemorrhage,and other events were followed up at the 3rd month of discharge.Results:In the experimental group,the inhibition rates of AA and ADP were significantly higher than those before treatment(both P<0.05).After treatment,the inhibition rates of AA and ADP in dual antiplatelet patients were higher than those of monoclonal antiplatelets(both P<0.05).The NIHSS score at discharge and the mRS score at the 3rd-month-follow-up in the experimental group were lower than those in the control group(both P<0.05).The incidences of stroke recurrence and hemorrhage events in the experimental group were lower than those in the control group(P<0.05).Conclusion:The application of a thrombelastogram in the detection of platelet inhibition rate to guide antiplatelet therapy in patients with acute non-cardiogenic stroke reduces the recurrences of cerebral infarction and the risk of hemorrhage and improves patients’clinical prognosis.展开更多
Neurological injury caused by ischemic stroke is a major cause of permanent disability and death. The currently available neuroprotective drugs fail to achieve desired therapeutic efficacy mainly due to short circulat...Neurological injury caused by ischemic stroke is a major cause of permanent disability and death. The currently available neuroprotective drugs fail to achieve desired therapeutic efficacy mainly due to short circulation half-life and poor blood−brain barrier (BBB) permeability. For that, an edaravone-loaded pH/glutathione (pH/GSH) dual-responsive poly(amino acid) nanogel (NG/EDA) was developed to improve the neuroprotection of EDA. The nanogel was triggered by acidic and EDA-induced high-level GSH microenvironments, which enabled the selective and sustained release of EDA at the site of ischemic injury. NG/EDA exhibited a uniform sub-spherical morphology with a mean hydrodynamic diameter of 112.3 ± 8.2 nm. NG/EDA efficiently accumulated at the cerebral ischemic injury site of permanent middle cerebral artery occlusion (pMCAO) mice, showing an efficient BBB crossing feature. Notably, NG/EDA with 50 µM EDA significantly increased neuron survival (29.3%) following oxygen and glucose deprivation by inhibiting ferroptosis. In addition, administering NG/EDA for 7 d significantly reduced infarct volume to 22.2% ± 7.2% and decreased neurobehavioral scores from 9.0 ± 0.6 to 2.0 ± 0.8. Such a pH/GSH dual-responsive nanoplatform might provide a unique and promising modality for neuroprotection in ischemic stroke and other central nervous system diseases.展开更多
The introduction of PARP inhibitors as active agents to inhibit the DNA repair was a revolution in the cancer therapeutics, however, such approach only has shown promising results for a short time in majority of cases...The introduction of PARP inhibitors as active agents to inhibit the DNA repair was a revolution in the cancer therapeutics, however, such approach only has shown promising results for a short time in majority of cases due to secondary mutations and promoter gene methylation, and most of patients with triple negative breast cancer when treated with such agents only benefit for a short time, until the tumor shows resistance and further the therapy fails [1]. Considering this category of drugs and their mechanism of action in DNA repair [2] [3], several recent studies have focused on combination of PARP inhibitors with chemotherapy, immune therapy and interestingly relevant to this article, epigenetic therapies [4]. That said, to our knowledge the human data in this regard is missing. Here we discuss a case report of a patient with stage four refractory and resistant BRCA1 mutated triple negative breast cancer who responded in matter of two weeks to a combinational therapy, consisting of PARP inhibitor and epigenetic therapies. As the patient already had exhausted the PARP inhibitor by excessive presence of BRCA positive altered circulatory DNA, the response merely reflects the epigenetic therapy as back bone of treatment. The liquid biopsy repeated after two weeks of combination therapy showed complete disappearance (resolution of positive BRCA gene/c DNA), reflecting a synergism by proposed modulation of resistance as mechanism of action. (The initial c DNA showed 93 percent mutation allele fraction of BRCA gene.) To our knowledge, this is the first study on combinational therapy in human. The finding in this case could potentially change the standard of care in treating BRCA positive tumors, by providing a superior treatment to current standards.展开更多
The reactive oxygen species(ROS)generation from photosensitizer in photodynamic therapy(PDT)is limited by tumor hypoxia.Even type-I photosensitizers,e.g.,sulfur-substituted Nile blue,still rely on oxygen as the main c...The reactive oxygen species(ROS)generation from photosensitizer in photodynamic therapy(PDT)is limited by tumor hypoxia.Even type-I photosensitizers,e.g.,sulfur-substituted Nile blue,still rely on oxygen as the main center for transferring electrons to generate ROS.Cutting off the pathway of oxygen consumption in tumor can help photosensitizers overcome the limitation of low oxygen,in order to efficiently generate more ROS.It is known that glycolysis inhibitor 3-bromopyruvic acid(3-BP),which could specially target mitochondria,can provide more oxygen by inhibiting oxidative phosphorylation.Herein,we successfully designed and synthesized a new 3-BP-coupled sulfur-substituted Nile blue as prodrug(NBBP)for chemical/photodynamic synergistic therapy.Major results indicated that the protons in tumor catalyzed the hydrolysis of NBBP,inhibited photoinduced electron transfer between 3-BP and the photosensitizer in NBBP and further assisted the photosensitizer to be localized in mitochondria,utilizing local oxygen as much as possible and kill tumor cells more efficiently.Moreover,the glycolysis inhibition-induced autophagy was combined with PDT-induced autophagy,which could promote the deaths of tumor cells.Unlike other remedies exploiting nanomaterials,this construction method of NBBP achieves the efficient synergy of photodynamic therapy and glycolysis inhibition,stronger than their theoretical addition,in spatiotemporal dimensions.Our study provides not only a highly efficient platform for tumor therapy but also a design approach for prodrugs with synergistic effects.展开更多
Autophagy is closely related to the drug resistance and metastasis in cancer therapy.Nanoparticlemediated co-delivery of combinatorial therapy with small-molecular drugs and nucleic acids is promising to address drug ...Autophagy is closely related to the drug resistance and metastasis in cancer therapy.Nanoparticlemediated co-delivery of combinatorial therapy with small-molecular drugs and nucleic acids is promising to address drug resistance.Here,a drug-delivering-drug(DDD)platform consisting of anti-tumor-drug nanorods as a vehicle for cytosol delivery of nucleic acid(miR-101)with potent autophagic-inhibition activity is reported for combinatorial therapy.The developed 180-nm nanoplatform,with total drug loading of up to 66%,delivers miR-101 to cancer cells,with threefold increase in intracellular level compared to conventional gene carriers and inhibits the autophagy significantly,along with above twofold reduction in LC3II mRNA and approximately fivefold increase in p62 mRNA over the control demonstrated in the results in vivo.And in turn,the delivery of miR-101 potentiates the drug’s ability to kill cancer cells,with a threefold increase in apoptosis over that of chemotherapy alone.The anti-tumor study in vivo indicates the combined therapy that enables a reduction of 80%in tumor volume and>twofold increase in apoptosis than of the single-drug strategy.In summary,via the carrier-free strategy of DDD,this work provides a delivery platform that can be easily customized to overcome drug resistance and facilitates the delivery of combined therapy of small-molecular drugs and nucleic acids.展开更多
Health-related quality-of-life (HRQOL) after a radical prostatectomy (RP) or extemal beam radiation therapy (EBRT) has not been studied in conjunction with oncological outcomes in relation to disease risk strati...Health-related quality-of-life (HRQOL) after a radical prostatectomy (RP) or extemal beam radiation therapy (EBRT) has not been studied in conjunction with oncological outcomes in relation to disease risk stratification. Moreover, the long-term outcomes of these treatment approaches have not been studied. We retrospectively analyzed oncological outcomes between consecutive patients receiving RP (n = 86) and EBRT (n = 76) for localized prostate cancer. HRQOL and functional outcomes could be assessed in 62 RP (79%) and 54 EBRT (79%) patients over a 3-year follow-up period (median: 41 months) using the Medical Outcomes Study Short Form-36 (SF-36) and the University of Califomia Los Angeles Prostate Cancer Index (UCLA PCI). The 5-year biochemical progression-free survival did not differ between the RP and EBRT groups for low-risk (74.6% vs. 75.0%, P = 0.931) and intermediate-risk (61.3% vs. 71.1%, P = 0.691) patients. For high-risk patients, progression-free survival was lower in the RP group (45.1%) than in the EBRT group (79.7%) (P = 0.002). The general HRQOL was comparable between the two groups. Regarding functional outcomes, the RP group reported lower scores on urinary function and less urinary bother and sexual bother than the EBRT group (P 〈 0.001, P 〈 0.05 and P 〈 0.001, respectively). With risk stratification, the low- and intermediate-risk patients in the RP group reported poorer urinary function than patients in the EBRT group (P 〈 0.001 for each). The sexual function of the high-risk patients in the EBRT group was better than that of the same risk RP patients (P 〈 0.001). Biochemical recurrence was not associated with the UCLA PCI score in either group. In conclusion, low- to intermediate-risk patients treated with an RP may report relatively decreased urinary function during long-term follow-up. The patient's HRQOL after treatment did not depend on biochemical recurrence.展开更多
To investigate the effects of long-term low dose hormone replacement therapy (HRT) on postmenopaosal women in homone level, cognition score, hippocampus volume, and magnetic resonance spectroscopy (MRS) parameters...To investigate the effects of long-term low dose hormone replacement therapy (HRT) on postmenopaosal women in homone level, cognition score, hippocampus volume, and magnetic resonance spectroscopy (MRS) parameters. Methods A total of 182 postmenopausal women aged 50-87 years were chosen at Peking Union Medical College Hospital and assigned to HRT group and control group. The volunteers of HRT group had taken low dose hormone [ estradiol (E2 ) 0. 5-1.0 mg and progesterone 0.5-2.0 mg, once a day ] for 4-33 years. The concentrations of E2, progesterone, and testosterone were measured using enzyme-linked immunosorbent assay (ELISA). The gene types of apolipoprotein E (ApoE) were measured by polymerase chain reaction, and the subjects with susceptible genes ( ApoE ε3/ε4) of Alzheimer's disease (AD) were screened. Their hippocampus volumes and MRS parameters were obtained through magnetic resonance imaging (MRI), and results in two groups were analyzed by statistical method. Results Compared with control group, the concentrations of E2 at each age stage in HRT group were significantly higher (P 〈0. 05) except the 80-89 years old subgroup; yet, there were no statistical differences in the concentrations of progesterone and testosterone between the two groups. There was no obvious difference in ApoE subtypes distribution between the two groups The results of hippocampus MRI for the subjects with susceptible genes ApoE ε3/ε4 (HRT group 14 cases, control group 11 cases) showed that the ratio of bilateral hippocampus volume to whole brain volume in HRT group (0. 406 ± 0.028) was signiticantlyhigher than control gronp (0.369±0.031, P〈0.05). Theresults of ^1H MRS for the subjects with susceptible genes ApoE ε3/ε4 ( HRT group 12 cases, control group 11 cases) showed that the N-acetylaspartate/total creatine at the area of hippocampus in HRT group ( 1.54±0. 08 ) were significantly higher than control group ( 1.45±0. 13, P 〈 0. 05). Conclusions For postmenopausal women, long-term low dose HRT can maintain the physiological concentration of E2 in plasma. Furthermore, the hippocampus MRI performed on those with ApoE ε3/ε3 genes shows that long-term low dose HRT can prevent hippocampus atrophy, which is beneficial to maintain the brain function and prevent AD.展开更多
singe unit discharge recordings were made from 42 WDR neurons in spinal dorsal horn in the rat. These neurons could he driven by electrical stimull activiting innocuous and noxious afferent fibres in the ipsilateral p...singe unit discharge recordings were made from 42 WDR neurons in spinal dorsal horn in the rat. These neurons could he driven by electrical stimull activiting innocuous and noxious afferent fibres in the ipsilateral plantar nerve. Traditional manual acupuncture delivered at the local acupoints Zusanli, Chengshan, Kunlun and Yongquan induced a strong inhibition or the C-fiber response. in 19 of 42 neurons obtained but did not after the A-fibre response of the neurons. The inhibition of the fibre response outlasted the period of acupuncture for more than 30 min. Neither Anor C-fibre responses in the remaining 23 neurous could be affected by manual acupuncture. These results suggest that the acupuncture stimulation specifically influences nociceptive nociceptive transmission,maybe through a presynaptic action,Furthermore, the fact that the inhibitory effect outlasts the stimulation by more than 30 min indicates that either a neuromodulatory ,presumably peptidergic action is at hand or that a temporary synaptic modification occurs in the spinal dorsal horn.展开更多
Sleep disturbance related symptoms are common in patients with long-term oxygen therapy (LTOT). Essentially, there were only few previous reports about the sleep architecture in patients with respiratory disease, such...Sleep disturbance related symptoms are common in patients with long-term oxygen therapy (LTOT). Essentially, there were only few previous reports about the sleep architecture in patients with respiratory disease, such as chronic obstructive pulmonary disease (COPD). This study aims to clarify the objective sleep state and the elements that affect sleep architecture in Chronic Respiratory Failure (CRF) patients with focus on clinical cases of chronic hypercapnia. 13 subjects with chronic respiratory failure were enrolled in the study. All the subjects were pre-evaluated by pulmonary function test and Arterial blood gas analysis (ABG) including exercise testing. Polysomnography (PSG) test was performed in each subject with supplemental oxygen. The estimated base line PaCO2 value that reflects overall PaCO2 including sleep period was calculated using equation of PaCO2[2.4×(HCOˉ3)-22]from obtained ABG value just before PSG test. 6 subjects were classified as hypercapnic group (base line PaCO2 ≥ 45 mmHg) and 7 subjects were non-hypercapnic group (base line PaCO2 < 45 mmHg). Latency persistent sleep of PSG data was significant higher in patients with hypercapnic than non-hypercapnic (p < 0.01). Periodic Limb Movement was seen in 23.6% of the subjects, however there was no contribution for arousals. Other PSG data include mean SpO2 were no significant difference. This study suggests that patients with estimated hypercapnia had more disturbed sleep architecture especially significant loss of sleep latency than non-hypercapnic patient with chronic respiratory failure under LTOT. Nocturnal PaCO2 level or ventilatory function may contribute to sleep disturbance in patients with estimated hypercapnia during LTOT.展开更多
Objective To evaluate the long-term outcome and prognostic factors of patients with nasopharyngeal carcinoma(NPC)from low-endemic regions of China who received definitive intensity-modulated radiation therapy(IMRT).Me...Objective To evaluate the long-term outcome and prognostic factors of patients with nasopharyngeal carcinoma(NPC)from low-endemic regions of China who received definitive intensity-modulated radiation therapy(IMRT).Methods The clinical data from 608 patients with newly-diagnosed non-metastatic NPC who have received initial treatment at our cancer center from January,2008 to December,2013 were retrospectively reviewed.All patients received definitive IMRT,and 87.7%received platinum-based chemotherapy.Results The median follow-up duration was 51 months(follow-up rate,98.5%;range,10–106 months)for the entire cohort.The 5-year overall survival rate was 79.7%.The 5-year local relapse-free survival rate,regional relapse-free survival rate,distant metastasis-free survival rate and progression-free survival rate were 92.4%,93.3%,79.2%and 74.3%,respectively.A total of 153 patients had experienced treatment failure,with distant metastasis as the primary cause in 77.1%(118/153).Patients with T4 or N3 diseases had a significantly poorer prognosis than other subcategories.Stage T4 and N3 were closely associated with distant metastasis,with the metastatic rate of 29.3%and 45.5%,respectively.Conclusion IMRT provides patients with non-metastatic NPC with satisfactory long-term survival.Both T stage and N stage are important prognostic factors for NPC patients.Patients with T4 or N3 diseases have significantly increased distant metastatic rates and poor survival time.展开更多
Objective:To evaluate the effect of existing acupuncture-related therapies on the longterm effects of post-stroke depression(PSD)by using a network meta-analysis with SSRIs as a common reference.Methods:The published ...Objective:To evaluate the effect of existing acupuncture-related therapies on the longterm effects of post-stroke depression(PSD)by using a network meta-analysis with SSRIs as a common reference.Methods:The published randomized controlled clinical trials of acupuncture-related therapies and SSRIs for PSD in PubMed,The Cochrane Library,EMbase,CNKI,CBM,VIP and wan-fang databases were comprehensively searched.The literature retrieval period was from The database establishment to July 31,2020.Cochrane Handbook 5.1.0 was used to assess the risk of bias in included studies.Data analysis is conducted through ADDIS,Review Manager 5.3,and STATA 13.1 software.Results:A total of 3115 patients with PSD were included in 30 RCTs,involving 10 therapeutic methods.Results of network meta-analysis showed that:in terms of total effective rate,body acupuncture+SSRIs was superior to body acupuncture[OR=2.85,95%CI(1.51,5.90)]and SSRIs[OR=5.37,95%CI(3.03,10.33)].In terms of HAMD score,body acupuncture+SSRIs was superior to body acupuncture[MD=1.69,95%CI(0.33,3.06)]and SSRIs[MD=3.87,95%CI(2.68,5.08)].The above ranking predicted that moxibustion+SSRIs was the best.In terms of NIHSS score,body acupuncture[MD=2.15,95%CI(1.10,3.26)]and body acupuncture+SSRIs[MD=1.77,95%CI(0.19,3.37)]were better than SSRIs.Conclusion:Moxibustion combined with SSRIs is the best for the long-term efficacy of acupuncture and moxibustion on PSD.Body acupuncture combined with SSRIs is better than SSRIs alone.The other therapies have their own advantages and disadvantages.Based on the defects of existing studies,this conclusion still needs to be verified by more high-quality RCTs.展开更多
In this research, some experimental measurements have been carried out to study the biological effects induced by laser irradiation on bacterial samples prepared by different ways and at different conditions. Consider...In this research, some experimental measurements have been carried out to study the biological effects induced by laser irradiation on bacterial samples prepared by different ways and at different conditions. Considering the induced samples, the effect of laser irradiation has been investigated through analyzing some of the properties of the transmitted and scattered laser beam for determining the stimulation or inhibition experienced by the investigated sample. In this study absorbance and scattering values have been measured as indicators of sample response to the irradiation laser beam. Absorbance and scattering have been investigated for different irradiation and sample parameters. Significant responses related to inhibition and stimulation effects of the investigated samples have been obtained. These results may significantly contribute in determining the effective utilization of the laser beam as a therapeutic tool for accelerating the wounds and burns healing of diabetic patients whom their response to anti-biotic is not appropriate. The simultaneous irradiation of samples with the use of anti-biotic shows significantly positive effect and fast response.展开更多
BACKGROUND The dynamic characteristics of glucose metabolism and its risk factors in patients living with human immunodeficiency virus(PLWH)who accepted primary treatment with the efavirenz(EFV)plus lamivudine(3TC)plu...BACKGROUND The dynamic characteristics of glucose metabolism and its risk factors in patients living with human immunodeficiency virus(PLWH)who accepted primary treatment with the efavirenz(EFV)plus lamivudine(3TC)plus tenofovir(TDF)(EFV+3TC+TDF)regimen are unclear and warrant investigation.AIM To study the long-term dynamic characteristics of glucose metabolism and its contributing factors in male PLWH who accepted primary treatment with the EFV+3TC+TDF regimen for 156 wk.METHODS This study was designed using a follow-up design.Sixty-one male treatmentnaive PLWH,including 50 cases with normal glucose tolerance and 11 cases with prediabetes,were treated with the EFV+3TC+TDF regimen for 156 wk.The glucose metabolism dynamic characteristics,the main risk factors and the differences among the three CD4+count groups were analyzed.RESULTS In treatment-naive male PLWH,regardless of whether glucose metabolism disorder was present at baseline,who accepted treatment with the EFV+3TC+TDF regimen for 156 wk,a continuous increase in the fasting plasma glucose(FPG)level,the rate of impaired fasting glucose(IFG)and the glycosylated hemoglobin(HbA1c)level were found.These changes were not due to insulin resistance but rather to significantly reduced isletβcell function,according to the homeostasis model assessment ofβcell function(HOMA-β).Moreover,the lower the baseline CD4+T-cell count was,the higher the FPG level and the lower the HOMA-βvalue.Furthermore,the main risk factors for the FPG levels were the CD3+CD8+cell count and viral load(VL),and the factors contributing to the HOMA-βvalues were the alanine aminotransferase level,VL and CD3+CD8+cell count.CONCLUSION These findings provide guidance to clinicians who are monitoring FPG levels closely and are concerned about IFG and decreased isletβcell function during antiretroviral therapy with the EFV+3TC+TDF regimen for long-term application.展开更多
To stduy the association between the prognosis of Ta transitional cell carcinoma (TCC) of the bladder and risk-related factors.Methods A total of 88 cases (62 males and 26 females;mean age,61 years;age range,41-81 yea...To stduy the association between the prognosis of Ta transitional cell carcinoma (TCC) of the bladder and risk-related factors.Methods A total of 88 cases (62 males and 26 females;mean age,61 years;age range,41-81 years) of initial T.TCC of the bladder treated with transurethral resection of bladder tumor (TURBt) plus intravesical chemotherapy or immunotherapy were enrolled.Among them,there were 26 cases of G1,61 cases of G2 and 1 case of G3.For tumor site,62 cases (16 cases of G1,45 of G2,1 of G3) had single tumor and 26 cases (10 cases of G1,16 of G2) had multi-site tumors.The mean follow-up was 113 months (range,56-168 months).The tumor grade,original tumor number and their association with the recurrence and progression of this type of TCC were retrospectively analyzed.Results The overall recurrence rate (RR) was 60% (53/88).In single tumor group,RR of G1 cases was 25% (4/16);RR of G2 cases was 62% (28/45) and the total RR was 52% (32/62).In multi-site tumor group,RR of G1 cases was 80% (8/10),RR of G2 cases was 75% (12/16) and the total RR was 77% (20/26).The RR of multi-site tumor group was significantly higher than that of single tumor group (P<0.01).In single tumor group,RR of G2 cases was significantly higher than that of G1 cases (P<0.001).In multi-site tumor group,there was no association of RR with tumor grade.There was no progression in G1 tumor cases.The progression rate was 42.5% (17/40) in G2 tumor cases;among them,30% (12/40) progressed to T1G2 tumors and 12.5% (5/40) progressed to T2G2 tumors.The RR of cases who received thiotepa,mitomycin and BCG were 75% (12/16),68% (30/44) and 40% (11/27),respectively.Tumor specific mortality was 1.14% (1/88,a T2G3 case).Conclusion The multi-site Ta TCC of the bladder has relatively higher RR and greater chance of progression after the treatment of TURBt plus intravesical chemotherapy or immunotherapy,especially in the poor differentiated tumors,thus active treatment and close follow-up are essential in clinical practice.9 refs.展开更多
文摘Objective:To investigate the effect of TSH inhibition therapy in the postoperative management of patients with differentiated thyroid cancer.Methods:Seventy patients diagnosed with differentiated thyroid cancer were selected for the study.TSH inhibition therapy was administered to the research group,while thyroxine replacement therapy was provided to the control group during the postoperative management phase.This allowed for a comparative analysis between the two groups.Results:In comparison with the control group,the research group exhibited significant decreases in serum TSH,T3,and T4 levels after treatment,while FT4 and FT3 levels significantly increased(P<0.05).Additionally,significant decreases in Tg,VEGF,TSGF,CD44V6,and sIL-2R levels were observed in the research group after treatment(P<0.05).No significant differences were found in pre-treatment thyroid function between the two groups(P>0.05).Conclusion:The application of TSH inhibition therapy in the postoperative management of patients with differentiated thyroid cancer demonstrates promising outcomes.
基金supported by an NIH grant to BOW (R01AR053293)the Van Andel Research Institutesupported in part by the National Research Foundation Singapore
文摘Dysregulated Wnt signaling is associated with the pathogenesis of cancers, fibrosis, and vascular diseases. Inhibition of Wnt signaling has shown efficacy in various pre-clinical models of these disorders. One of the key challenges in developing targeted anti-cancer drugs is to balance efficacy with on-target toxicity. Given the crucial role Wnts play in the differentiation of osteoblasts and osteoclasts, acute inhibition of Wnt signaling is likely to affect bone homeostasis. In this study, we evaluated the skeletal effect of small molecule inhibitor of an o-acyl transferase porcupine(PORCN) that prevents Wnt signaling by blocking the secretion of all Wnts. Micro-computed tomography and histomorphometric evaluation revealed that the bones of mice treated with two structurally distinct PORCN inhibitors LGK974 and ETC-1922159(ETC-159) had loss-of-bone volume and density within 4 weeks of exposure. This decreased bone mass was associated with a significant increase in adipocytes within the bone marrow. Notably,simultaneous administration of a clinically approved anti-resorptive, alendronate, a member of the bisphosphonate family,mitigated loss-of-bone mass seen upon ETC-159 treatment by regulating activity of osteoclasts and blocking accumulation of bone marrow adipocytes. Our results support the addition of bone protective agents when treating patients with PORCN inhibitors.Mitigation of bone toxicity can extend the therapeutic utility of Wnt pathway inhibitors.
文摘Objective:To investigate the application value of thrombelastogram(TEG)in the detection of platelet inhibition rate for antiplatelet therapy for acute non-cardiogenic stroke.Methods:A total of 100 patients with ischemic non-cardiogenic stroke were selected for this study from September 2020 to October 2021.Patients were randomly divided into experimental group and control group,with 50 cases for each group.Before and after 1 week of antiplatelet drug treatment,the platelet inhibition rate in the experimental group was measured with arachidonic acid(AA)and adenosine diphosphate(ADP)by TEG;no platelet inhibition rates detection was conducted for the control group.The dose and type of drugs were adjusted for the experimental group according to the platelet functions and medication based on the clinical experience conducted for the control group.The neurological deficits of the discharged patients were scored with NIHSS score,mRS score,stroke recurrence,hemorrhage,and other events were followed up at the 3rd month of discharge.Results:In the experimental group,the inhibition rates of AA and ADP were significantly higher than those before treatment(both P<0.05).After treatment,the inhibition rates of AA and ADP in dual antiplatelet patients were higher than those of monoclonal antiplatelets(both P<0.05).The NIHSS score at discharge and the mRS score at the 3rd-month-follow-up in the experimental group were lower than those in the control group(both P<0.05).The incidences of stroke recurrence and hemorrhage events in the experimental group were lower than those in the control group(P<0.05).Conclusion:The application of a thrombelastogram in the detection of platelet inhibition rate to guide antiplatelet therapy in patients with acute non-cardiogenic stroke reduces the recurrences of cerebral infarction and the risk of hemorrhage and improves patients’clinical prognosis.
基金supported by the National Natural Science Foundation of China(Grant No.U23A20591,52203201,52173149,and 81971174)the Youth Talents Promotion Project of Jilin Province(Grant No.202019)+1 种基金the Science and Technology Development Program of Jilin Province(Grant No.20210101114JC)Research Cooperation Platform Project of Sino-Japanese Friendship Hospital of Jilin University and Basic Medical School of Jilin University(Grant No.KYXZ2022JC04).
文摘Neurological injury caused by ischemic stroke is a major cause of permanent disability and death. The currently available neuroprotective drugs fail to achieve desired therapeutic efficacy mainly due to short circulation half-life and poor blood−brain barrier (BBB) permeability. For that, an edaravone-loaded pH/glutathione (pH/GSH) dual-responsive poly(amino acid) nanogel (NG/EDA) was developed to improve the neuroprotection of EDA. The nanogel was triggered by acidic and EDA-induced high-level GSH microenvironments, which enabled the selective and sustained release of EDA at the site of ischemic injury. NG/EDA exhibited a uniform sub-spherical morphology with a mean hydrodynamic diameter of 112.3 ± 8.2 nm. NG/EDA efficiently accumulated at the cerebral ischemic injury site of permanent middle cerebral artery occlusion (pMCAO) mice, showing an efficient BBB crossing feature. Notably, NG/EDA with 50 µM EDA significantly increased neuron survival (29.3%) following oxygen and glucose deprivation by inhibiting ferroptosis. In addition, administering NG/EDA for 7 d significantly reduced infarct volume to 22.2% ± 7.2% and decreased neurobehavioral scores from 9.0 ± 0.6 to 2.0 ± 0.8. Such a pH/GSH dual-responsive nanoplatform might provide a unique and promising modality for neuroprotection in ischemic stroke and other central nervous system diseases.
文摘The introduction of PARP inhibitors as active agents to inhibit the DNA repair was a revolution in the cancer therapeutics, however, such approach only has shown promising results for a short time in majority of cases due to secondary mutations and promoter gene methylation, and most of patients with triple negative breast cancer when treated with such agents only benefit for a short time, until the tumor shows resistance and further the therapy fails [1]. Considering this category of drugs and their mechanism of action in DNA repair [2] [3], several recent studies have focused on combination of PARP inhibitors with chemotherapy, immune therapy and interestingly relevant to this article, epigenetic therapies [4]. That said, to our knowledge the human data in this regard is missing. Here we discuss a case report of a patient with stage four refractory and resistant BRCA1 mutated triple negative breast cancer who responded in matter of two weeks to a combinational therapy, consisting of PARP inhibitor and epigenetic therapies. As the patient already had exhausted the PARP inhibitor by excessive presence of BRCA positive altered circulatory DNA, the response merely reflects the epigenetic therapy as back bone of treatment. The liquid biopsy repeated after two weeks of combination therapy showed complete disappearance (resolution of positive BRCA gene/c DNA), reflecting a synergism by proposed modulation of resistance as mechanism of action. (The initial c DNA showed 93 percent mutation allele fraction of BRCA gene.) To our knowledge, this is the first study on combinational therapy in human. The finding in this case could potentially change the standard of care in treating BRCA positive tumors, by providing a superior treatment to current standards.
基金supported by the National Natural Science Foundation of China(22108024)the Dalian High-level Talent Innovation Support Program of China(2022RQ016)the Fundamental Research Funds for the Central Universities(DUT22LAB601)。
文摘The reactive oxygen species(ROS)generation from photosensitizer in photodynamic therapy(PDT)is limited by tumor hypoxia.Even type-I photosensitizers,e.g.,sulfur-substituted Nile blue,still rely on oxygen as the main center for transferring electrons to generate ROS.Cutting off the pathway of oxygen consumption in tumor can help photosensitizers overcome the limitation of low oxygen,in order to efficiently generate more ROS.It is known that glycolysis inhibitor 3-bromopyruvic acid(3-BP),which could specially target mitochondria,can provide more oxygen by inhibiting oxidative phosphorylation.Herein,we successfully designed and synthesized a new 3-BP-coupled sulfur-substituted Nile blue as prodrug(NBBP)for chemical/photodynamic synergistic therapy.Major results indicated that the protons in tumor catalyzed the hydrolysis of NBBP,inhibited photoinduced electron transfer between 3-BP and the photosensitizer in NBBP and further assisted the photosensitizer to be localized in mitochondria,utilizing local oxygen as much as possible and kill tumor cells more efficiently.Moreover,the glycolysis inhibition-induced autophagy was combined with PDT-induced autophagy,which could promote the deaths of tumor cells.Unlike other remedies exploiting nanomaterials,this construction method of NBBP achieves the efficient synergy of photodynamic therapy and glycolysis inhibition,stronger than their theoretical addition,in spatiotemporal dimensions.Our study provides not only a highly efficient platform for tumor therapy but also a design approach for prodrugs with synergistic effects.
基金supported by Grants from the National Natural Science Foundation of China(Nos.81872823,81871477)the Ministry of Science and Technology of China(2017ZX09101001-004)+1 种基金the Double First-Class(CPU2018PZQ13)of CPUthe Key Members of the Outstanding Young Teacher of Jiangsu Qing Lan Project(2016).
文摘Autophagy is closely related to the drug resistance and metastasis in cancer therapy.Nanoparticlemediated co-delivery of combinatorial therapy with small-molecular drugs and nucleic acids is promising to address drug resistance.Here,a drug-delivering-drug(DDD)platform consisting of anti-tumor-drug nanorods as a vehicle for cytosol delivery of nucleic acid(miR-101)with potent autophagic-inhibition activity is reported for combinatorial therapy.The developed 180-nm nanoplatform,with total drug loading of up to 66%,delivers miR-101 to cancer cells,with threefold increase in intracellular level compared to conventional gene carriers and inhibits the autophagy significantly,along with above twofold reduction in LC3II mRNA and approximately fivefold increase in p62 mRNA over the control demonstrated in the results in vivo.And in turn,the delivery of miR-101 potentiates the drug’s ability to kill cancer cells,with a threefold increase in apoptosis over that of chemotherapy alone.The anti-tumor study in vivo indicates the combined therapy that enables a reduction of 80%in tumor volume and>twofold increase in apoptosis than of the single-drug strategy.In summary,via the carrier-free strategy of DDD,this work provides a delivery platform that can be easily customized to overcome drug resistance and facilitates the delivery of combined therapy of small-molecular drugs and nucleic acids.
文摘Health-related quality-of-life (HRQOL) after a radical prostatectomy (RP) or extemal beam radiation therapy (EBRT) has not been studied in conjunction with oncological outcomes in relation to disease risk stratification. Moreover, the long-term outcomes of these treatment approaches have not been studied. We retrospectively analyzed oncological outcomes between consecutive patients receiving RP (n = 86) and EBRT (n = 76) for localized prostate cancer. HRQOL and functional outcomes could be assessed in 62 RP (79%) and 54 EBRT (79%) patients over a 3-year follow-up period (median: 41 months) using the Medical Outcomes Study Short Form-36 (SF-36) and the University of Califomia Los Angeles Prostate Cancer Index (UCLA PCI). The 5-year biochemical progression-free survival did not differ between the RP and EBRT groups for low-risk (74.6% vs. 75.0%, P = 0.931) and intermediate-risk (61.3% vs. 71.1%, P = 0.691) patients. For high-risk patients, progression-free survival was lower in the RP group (45.1%) than in the EBRT group (79.7%) (P = 0.002). The general HRQOL was comparable between the two groups. Regarding functional outcomes, the RP group reported lower scores on urinary function and less urinary bother and sexual bother than the EBRT group (P 〈 0.001, P 〈 0.05 and P 〈 0.001, respectively). With risk stratification, the low- and intermediate-risk patients in the RP group reported poorer urinary function than patients in the EBRT group (P 〈 0.001 for each). The sexual function of the high-risk patients in the EBRT group was better than that of the same risk RP patients (P 〈 0.001). Biochemical recurrence was not associated with the UCLA PCI score in either group. In conclusion, low- to intermediate-risk patients treated with an RP may report relatively decreased urinary function during long-term follow-up. The patient's HRQOL after treatment did not depend on biochemical recurrence.
文摘To investigate the effects of long-term low dose hormone replacement therapy (HRT) on postmenopaosal women in homone level, cognition score, hippocampus volume, and magnetic resonance spectroscopy (MRS) parameters. Methods A total of 182 postmenopausal women aged 50-87 years were chosen at Peking Union Medical College Hospital and assigned to HRT group and control group. The volunteers of HRT group had taken low dose hormone [ estradiol (E2 ) 0. 5-1.0 mg and progesterone 0.5-2.0 mg, once a day ] for 4-33 years. The concentrations of E2, progesterone, and testosterone were measured using enzyme-linked immunosorbent assay (ELISA). The gene types of apolipoprotein E (ApoE) were measured by polymerase chain reaction, and the subjects with susceptible genes ( ApoE ε3/ε4) of Alzheimer's disease (AD) were screened. Their hippocampus volumes and MRS parameters were obtained through magnetic resonance imaging (MRI), and results in two groups were analyzed by statistical method. Results Compared with control group, the concentrations of E2 at each age stage in HRT group were significantly higher (P 〈0. 05) except the 80-89 years old subgroup; yet, there were no statistical differences in the concentrations of progesterone and testosterone between the two groups. There was no obvious difference in ApoE subtypes distribution between the two groups The results of hippocampus MRI for the subjects with susceptible genes ApoE ε3/ε4 (HRT group 14 cases, control group 11 cases) showed that the ratio of bilateral hippocampus volume to whole brain volume in HRT group (0. 406 ± 0.028) was signiticantlyhigher than control gronp (0.369±0.031, P〈0.05). Theresults of ^1H MRS for the subjects with susceptible genes ApoE ε3/ε4 ( HRT group 12 cases, control group 11 cases) showed that the N-acetylaspartate/total creatine at the area of hippocampus in HRT group ( 1.54±0. 08 ) were significantly higher than control group ( 1.45±0. 13, P 〈 0. 05). Conclusions For postmenopausal women, long-term low dose HRT can maintain the physiological concentration of E2 in plasma. Furthermore, the hippocampus MRI performed on those with ApoE ε3/ε3 genes shows that long-term low dose HRT can prevent hippocampus atrophy, which is beneficial to maintain the brain function and prevent AD.
文摘singe unit discharge recordings were made from 42 WDR neurons in spinal dorsal horn in the rat. These neurons could he driven by electrical stimull activiting innocuous and noxious afferent fibres in the ipsilateral plantar nerve. Traditional manual acupuncture delivered at the local acupoints Zusanli, Chengshan, Kunlun and Yongquan induced a strong inhibition or the C-fiber response. in 19 of 42 neurons obtained but did not after the A-fibre response of the neurons. The inhibition of the fibre response outlasted the period of acupuncture for more than 30 min. Neither Anor C-fibre responses in the remaining 23 neurous could be affected by manual acupuncture. These results suggest that the acupuncture stimulation specifically influences nociceptive nociceptive transmission,maybe through a presynaptic action,Furthermore, the fact that the inhibitory effect outlasts the stimulation by more than 30 min indicates that either a neuromodulatory ,presumably peptidergic action is at hand or that a temporary synaptic modification occurs in the spinal dorsal horn.
文摘Sleep disturbance related symptoms are common in patients with long-term oxygen therapy (LTOT). Essentially, there were only few previous reports about the sleep architecture in patients with respiratory disease, such as chronic obstructive pulmonary disease (COPD). This study aims to clarify the objective sleep state and the elements that affect sleep architecture in Chronic Respiratory Failure (CRF) patients with focus on clinical cases of chronic hypercapnia. 13 subjects with chronic respiratory failure were enrolled in the study. All the subjects were pre-evaluated by pulmonary function test and Arterial blood gas analysis (ABG) including exercise testing. Polysomnography (PSG) test was performed in each subject with supplemental oxygen. The estimated base line PaCO2 value that reflects overall PaCO2 including sleep period was calculated using equation of PaCO2[2.4×(HCOˉ3)-22]from obtained ABG value just before PSG test. 6 subjects were classified as hypercapnic group (base line PaCO2 ≥ 45 mmHg) and 7 subjects were non-hypercapnic group (base line PaCO2 < 45 mmHg). Latency persistent sleep of PSG data was significant higher in patients with hypercapnic than non-hypercapnic (p < 0.01). Periodic Limb Movement was seen in 23.6% of the subjects, however there was no contribution for arousals. Other PSG data include mean SpO2 were no significant difference. This study suggests that patients with estimated hypercapnia had more disturbed sleep architecture especially significant loss of sleep latency than non-hypercapnic patient with chronic respiratory failure under LTOT. Nocturnal PaCO2 level or ventilatory function may contribute to sleep disturbance in patients with estimated hypercapnia during LTOT.
文摘Objective To evaluate the long-term outcome and prognostic factors of patients with nasopharyngeal carcinoma(NPC)from low-endemic regions of China who received definitive intensity-modulated radiation therapy(IMRT).Methods The clinical data from 608 patients with newly-diagnosed non-metastatic NPC who have received initial treatment at our cancer center from January,2008 to December,2013 were retrospectively reviewed.All patients received definitive IMRT,and 87.7%received platinum-based chemotherapy.Results The median follow-up duration was 51 months(follow-up rate,98.5%;range,10–106 months)for the entire cohort.The 5-year overall survival rate was 79.7%.The 5-year local relapse-free survival rate,regional relapse-free survival rate,distant metastasis-free survival rate and progression-free survival rate were 92.4%,93.3%,79.2%and 74.3%,respectively.A total of 153 patients had experienced treatment failure,with distant metastasis as the primary cause in 77.1%(118/153).Patients with T4 or N3 diseases had a significantly poorer prognosis than other subcategories.Stage T4 and N3 were closely associated with distant metastasis,with the metastatic rate of 29.3%and 45.5%,respectively.Conclusion IMRT provides patients with non-metastatic NPC with satisfactory long-term survival.Both T stage and N stage are important prognostic factors for NPC patients.Patients with T4 or N3 diseases have significantly increased distant metastatic rates and poor survival time.
基金National Natural Science Foundation of China(No.81873384)。
文摘Objective:To evaluate the effect of existing acupuncture-related therapies on the longterm effects of post-stroke depression(PSD)by using a network meta-analysis with SSRIs as a common reference.Methods:The published randomized controlled clinical trials of acupuncture-related therapies and SSRIs for PSD in PubMed,The Cochrane Library,EMbase,CNKI,CBM,VIP and wan-fang databases were comprehensively searched.The literature retrieval period was from The database establishment to July 31,2020.Cochrane Handbook 5.1.0 was used to assess the risk of bias in included studies.Data analysis is conducted through ADDIS,Review Manager 5.3,and STATA 13.1 software.Results:A total of 3115 patients with PSD were included in 30 RCTs,involving 10 therapeutic methods.Results of network meta-analysis showed that:in terms of total effective rate,body acupuncture+SSRIs was superior to body acupuncture[OR=2.85,95%CI(1.51,5.90)]and SSRIs[OR=5.37,95%CI(3.03,10.33)].In terms of HAMD score,body acupuncture+SSRIs was superior to body acupuncture[MD=1.69,95%CI(0.33,3.06)]and SSRIs[MD=3.87,95%CI(2.68,5.08)].The above ranking predicted that moxibustion+SSRIs was the best.In terms of NIHSS score,body acupuncture[MD=2.15,95%CI(1.10,3.26)]and body acupuncture+SSRIs[MD=1.77,95%CI(0.19,3.37)]were better than SSRIs.Conclusion:Moxibustion combined with SSRIs is the best for the long-term efficacy of acupuncture and moxibustion on PSD.Body acupuncture combined with SSRIs is better than SSRIs alone.The other therapies have their own advantages and disadvantages.Based on the defects of existing studies,this conclusion still needs to be verified by more high-quality RCTs.
文摘In this research, some experimental measurements have been carried out to study the biological effects induced by laser irradiation on bacterial samples prepared by different ways and at different conditions. Considering the induced samples, the effect of laser irradiation has been investigated through analyzing some of the properties of the transmitted and scattered laser beam for determining the stimulation or inhibition experienced by the investigated sample. In this study absorbance and scattering values have been measured as indicators of sample response to the irradiation laser beam. Absorbance and scattering have been investigated for different irradiation and sample parameters. Significant responses related to inhibition and stimulation effects of the investigated samples have been obtained. These results may significantly contribute in determining the effective utilization of the laser beam as a therapeutic tool for accelerating the wounds and burns healing of diabetic patients whom their response to anti-biotic is not appropriate. The simultaneous irradiation of samples with the use of anti-biotic shows significantly positive effect and fast response.
基金Supported by The Twelfth Five-Year Project on Tackling Key Problems of National Science and Technology,No2012ZX10001-003Sichuan Province Health Commission,No. 130430 and No. 17PJ070Chengdu Municipal Health Commission,No. 2019079
文摘BACKGROUND The dynamic characteristics of glucose metabolism and its risk factors in patients living with human immunodeficiency virus(PLWH)who accepted primary treatment with the efavirenz(EFV)plus lamivudine(3TC)plus tenofovir(TDF)(EFV+3TC+TDF)regimen are unclear and warrant investigation.AIM To study the long-term dynamic characteristics of glucose metabolism and its contributing factors in male PLWH who accepted primary treatment with the EFV+3TC+TDF regimen for 156 wk.METHODS This study was designed using a follow-up design.Sixty-one male treatmentnaive PLWH,including 50 cases with normal glucose tolerance and 11 cases with prediabetes,were treated with the EFV+3TC+TDF regimen for 156 wk.The glucose metabolism dynamic characteristics,the main risk factors and the differences among the three CD4+count groups were analyzed.RESULTS In treatment-naive male PLWH,regardless of whether glucose metabolism disorder was present at baseline,who accepted treatment with the EFV+3TC+TDF regimen for 156 wk,a continuous increase in the fasting plasma glucose(FPG)level,the rate of impaired fasting glucose(IFG)and the glycosylated hemoglobin(HbA1c)level were found.These changes were not due to insulin resistance but rather to significantly reduced isletβcell function,according to the homeostasis model assessment ofβcell function(HOMA-β).Moreover,the lower the baseline CD4+T-cell count was,the higher the FPG level and the lower the HOMA-βvalue.Furthermore,the main risk factors for the FPG levels were the CD3+CD8+cell count and viral load(VL),and the factors contributing to the HOMA-βvalues were the alanine aminotransferase level,VL and CD3+CD8+cell count.CONCLUSION These findings provide guidance to clinicians who are monitoring FPG levels closely and are concerned about IFG and decreased isletβcell function during antiretroviral therapy with the EFV+3TC+TDF regimen for long-term application.
文摘To stduy the association between the prognosis of Ta transitional cell carcinoma (TCC) of the bladder and risk-related factors.Methods A total of 88 cases (62 males and 26 females;mean age,61 years;age range,41-81 years) of initial T.TCC of the bladder treated with transurethral resection of bladder tumor (TURBt) plus intravesical chemotherapy or immunotherapy were enrolled.Among them,there were 26 cases of G1,61 cases of G2 and 1 case of G3.For tumor site,62 cases (16 cases of G1,45 of G2,1 of G3) had single tumor and 26 cases (10 cases of G1,16 of G2) had multi-site tumors.The mean follow-up was 113 months (range,56-168 months).The tumor grade,original tumor number and their association with the recurrence and progression of this type of TCC were retrospectively analyzed.Results The overall recurrence rate (RR) was 60% (53/88).In single tumor group,RR of G1 cases was 25% (4/16);RR of G2 cases was 62% (28/45) and the total RR was 52% (32/62).In multi-site tumor group,RR of G1 cases was 80% (8/10),RR of G2 cases was 75% (12/16) and the total RR was 77% (20/26).The RR of multi-site tumor group was significantly higher than that of single tumor group (P<0.01).In single tumor group,RR of G2 cases was significantly higher than that of G1 cases (P<0.001).In multi-site tumor group,there was no association of RR with tumor grade.There was no progression in G1 tumor cases.The progression rate was 42.5% (17/40) in G2 tumor cases;among them,30% (12/40) progressed to T1G2 tumors and 12.5% (5/40) progressed to T2G2 tumors.The RR of cases who received thiotepa,mitomycin and BCG were 75% (12/16),68% (30/44) and 40% (11/27),respectively.Tumor specific mortality was 1.14% (1/88,a T2G3 case).Conclusion The multi-site Ta TCC of the bladder has relatively higher RR and greater chance of progression after the treatment of TURBt plus intravesical chemotherapy or immunotherapy,especially in the poor differentiated tumors,thus active treatment and close follow-up are essential in clinical practice.9 refs.