TiClx (x=2.17) was prepared by using titanium sponge to reduce the concentration of TiCl4 in a NaCl-KCl melt under negative pressure. The as-prepared NaCl-KCl-TiClx melt was employed as the electrolyte, and two para...TiClx (x=2.17) was prepared by using titanium sponge to reduce the concentration of TiCl4 in a NaCl-KCl melt under negative pressure. The as-prepared NaCl-KCl-TiClx melt was employed as the electrolyte, and two parallel crude titanium plates and one high-purity titanium plate were used as the anode and cathode, respectively. A series of electrochemical tests were performed to investigate the influence of electrolytic parameters on the current efficiency and quality of cathodic products. The results indicated that the quality of cathodic products was related to the current efficiency, which is significantly dependent on the current density and the initial concentration of titanium ions. The significance of this study is the attainment of high-purity titanium with a low oxygen content of 30× 10^-6.展开更多
AIM:To explore the influencing factors of diabetes type 2 patients with mild non-proliferative diabetic retinopathy(NPDR)in the Kailuan area of Tangshan,Hebei Province,China.METHODS:In this non-interventional,retrospe...AIM:To explore the influencing factors of diabetes type 2 patients with mild non-proliferative diabetic retinopathy(NPDR)in the Kailuan area of Tangshan,Hebei Province,China.METHODS:In this non-interventional,retrospective study,683 patients with type 2 diabetes were included in the Kailuan Diabetic Retinopathy Study involving participants with diabetes in the community-based longitudinal Kailuan Study.Based on the undilated ultrawide field(200°;UWF)images and partial dilated digital fundus images,the diabetic retinopathy(DR)of the surveyed population was graded.Interobserver agreement was estimated by using Cohen’s Kappa statistics.The main outcome indicators included gender,age,weight,height,body mass index,blood pressure,circumferences of neck,waist and hip,current smoking,levels of fasting plasma glucose(FPG),hypersensitive C-reactive protein,creatinine,and cholesterol,etc.According to different lesions’locations of patients with mild NPDR,logistic regression models were used to estimate the odds ratios(ORs)and their 95%Cls of each risk factor.RESULTS:The study group of 683 patients included 570 males and 113 females.The mean age of the patients was62.18±9.41 y.Compared with dilated fundus examinations,there was fair agreement with the level of DR identified on UWF images in 63.91%of eyes(k=0.369,95%CI,0.00-0.00).Detected by UWF images,there were 98 patients with mild NPDR having peripheral retinal lesions,35 patients with mild NPDR having posterior lesions,44 patients with mild NPDR whose lesions were detected both in and out the standard two fields area,and 336 patients with non obvious DR.Parameters that conferred a statistically significant increased risks for mild NPDR with having peripheral retinal lesions were neck circumstance(OR,1.124;95%CI,1.044-1.211),and with posterior lesions were FPG(OR,1.052;95%CI,1.007-1.099).CONCLUSION:UWF is an effectiveness means of DR screening.Moreover,it is necessary to evaluate peripheral diabetic retinal lesions which can help to estimate the severity of DR.The phenomenon that nonuniform and inhomogeneous distribution of DR lesions has been found.And the influencing factors in mild NPDR are differing by different lesions’locations.展开更多
AIM: To examine the expression of Twik-related K+ channel 1(TREK-1), Twik-related K+ channel 2(TREK-2), and Twik-related arachidonic acid-stimulated K+ channel(TRAAK) in the retina of adult rd1 mice and to detect the ...AIM: To examine the expression of Twik-related K+ channel 1(TREK-1), Twik-related K+ channel 2(TREK-2), and Twik-related arachidonic acid-stimulated K+ channel(TRAAK) in the retina of adult rd1 mice and to detect the protective roles of TREK-TRAAK two-pore-domain K+(K2P) channels against retinal degeneration.METHODS: Twenty-eight-day-old C57BL/6J mice and 28-day-old rd1 mice were used in this study. Retinal protein, retinal RNA, and embedded eyeballs were prepared from these two groups of mice. Real-time quantitative polymerase chain reaction and Western blot analyses were used to assess the gene transcription and protein levels, respectively. Retinal structures were observed using hematoxylin and eosin(H&E) staining. Immunohistochemistry was utilized to observe the retinal localization of TREK-TRAAK channels. Current changes in retinal ganglion cells(RGCs) after activation of TREK-TRAAK channels were examined using a patchclamp technique. RESULTS: Compared with C57BL/6J mice, rd1 mice exhibited significantly higher retinal mRNA and protein expression levels of TREK-1, TREK-2, and TRAAK channels. In both groups, immunohistochemistry showed expression of TREK-TRAAK channels in retinal layers. After addition of the TREK-TRAAK channel agonist arachidonic acid(AA), whole-cell voltage step evoked currents were significantly higher in RGCs from rd1 mice than in RGCs from control C57BL/6J mice, suggesting that TREK-TRAAK channels were opened in RGCs from rd1 mice. CONCLUSION: TREK-TRAAK K2P channels’ expression is increased in adult rd1 mice. AA induced the opening of TREK-TRAAK K2P channels in adult rd1 mice and may thus counterbalance depolarization of RGCs and protect the retina from excitotoxicity. TREK-TRAAK channels may play a protective role against retinal degeneration.展开更多
AIM: To observe and compare the statistical significance of superficial and deep vascular leakage in the pathological changes of the diabetic rats retina after the Evans blue(EB) perfusion, and utilize the modified wh...AIM: To observe and compare the statistical significance of superficial and deep vascular leakage in the pathological changes of the diabetic rats retina after the Evans blue(EB) perfusion, and utilize the modified whole-retina spreading method to make the slides while protecting the periphery of the retina. METHODS: The Sprague-Dawley(SD) rats were randomly divided into 6 groups. Each group named as the normal groups for 4, 8, and 12 wk and the diabetic groups for 4, 8, and 12 wk. The EB was injected into the cardiovascular system of the rats at the different time points. The retina of each group was obtained for observation.RESULTS: The superficial vascular leakage was found in all 6 groups. The size of leakage area of superficial retinal blood vessels was(0.54±0.23)%,(0.65±0.11)%,and(0.58±0.10)% in normal group. No notable leakage was found in the deep blood vessels [(0.03±0.04)%,(0.03±0.05)%, and(0.03±0.05)%]. The deep retinal vascular leakage was found in the peripheral retina of diabetic rats. The size of leakage area of superficial retinal blood vessels in diabetic group were(0.53±0.22)%,(0.69±0.16)%, and(0.52±0.11)%. The leakage areas of deep blood vessels were(0.54±0.50)%,(1.42±0.16)%, and(1.80±0.07)% at 4, 8, and 12 wk, respectively. There was a statistically difference of the leakage area between the 8 th week and the 4 th week of diabetes group(P=0.003). The statistically significant difference between the diabetes and the control groups was noted at 4 wk and 8 wk(P<0.001).CONCLUSION: The main retinal pathological changes of early-stage diabetic rats are the vascular leakage of the periphery of deep retina. Diabetic rats modeled after 8 wk have semi-quantitative statistical difference compared with the normal rats, thus early intervention treatment research can start at this time point.展开更多
AIM: To investigate the expression of TWIK-related arachidonic acid-stimulated K+ channel(TRAAK) in retinal degeneration mice(rd1) and further evaluate how TRAAK affect photoreceptor cell apoptosis.METHODS: The rd1 mi...AIM: To investigate the expression of TWIK-related arachidonic acid-stimulated K+ channel(TRAAK) in retinal degeneration mice(rd1) and further evaluate how TRAAK affect photoreceptor cell apoptosis.METHODS: The rd1 mice were distributed into blank(no treatment), control(1.4% DMSO, intraperitoneal injection) and riluzole groups(4 mg/kg·d, intraperitoneal injection) from postnatal 7 d to 10, 14 and 18 d;C57 group(no treatment), as age-matched wild-type control. The thickness of the outer nuclear layer(ONL) of retina was detected by paraffin section hematoxylin and eosin staining. The expression of TRAAK and the apoptosis of the ONL cells were detected by immunostaining, Western blotting, and real-time polymerase chain reaction. RESULTS: The channel agonist riluzole activated TRAAK and delayed the apoptosis of photoreceptor cells in ONL layer of rd1 mice. Both at mRNA and protein levels, after riluzole treatment, TRAAK expression was significantly upregulated, when compared with the control and blank group. Then we detected a series of apoptosis related mRNA and protein. The anti-apoptotic factor Bcl-2 downregulated and the pro-apoptotic factors Bax and cleaved-caspase-3 upregulated significantly. CONCLUSION: Riluzole elevates the expression of TRAAK and inhibits the development of apoptosis. Activation of TRAAK may have some potential effects to put off photoreceptor apoptosis.展开更多
BACKGROUND Oxidized low-density lipoprotein(ox-LDL),which is abnormally increased in the serum of colorectal cancer(CRC)patients consuming a high-fat diet(HFD),may be one of the risk factors for the development of CRC...BACKGROUND Oxidized low-density lipoprotein(ox-LDL),which is abnormally increased in the serum of colorectal cancer(CRC)patients consuming a high-fat diet(HFD),may be one of the risk factors for the development of CRC.Ox-LDL exerts a regulatory effect on macrophages and may influence CRC through the tumor microenvironment.The role of ox-LDL in CRC remains unclear.AIM To investigate the role of ox-LDL through macrophages in HFD associated CRC.METHODS The expression of ox-LDL and CD206 was detected in colorectal tissues of CRC patients with hyperlipidemia and HFD-fed mice by immunofluorescence.We stimulated the macrophages with 20μg/mL ox-LDL and assessed the expression levels of CD206 and the cytokines by cell fluorescence and quantitative polymerase chain reaction.We further knocked down LOX-1,the surface receptor of ox-LDL,to confirm the function of ox-LDL in macrophages.Then,LoVo cells were co-cultured with the stimulated macrophages to analyze the CD44 and CD133 expression by western blot.RESULTS The expression of ox-LDL and the CD206 was significantly increased in the stroma of colorectal tissues of CRC patients with hyperlipidemia,and also upregulated in the HFD-fed mice.Moreover,an increased level of CD206 and decreased level of inducible nitric oxide synthase were observed in macrophages after ox-LDL continuous stimulation.Such effects were inhibited when the surface receptor LOX-1 was knocked down in macrophages.Ox-LDL could induce CD206+macrophages,which resulted in high expression of CD44 and CD133 in co-cultured LoVo cells.CONCLUSION Ox-LDL stimulates CD206+macrophages to upregulate CD44 and CD133 expression in HFD related CRC.展开更多
Hybrid quantum system of negatively charged nitrogen–vacancy(NV^-) centers in diamond and superconducting qubits provide the possibility to extend the performances of both systems. In this work, we numerically simu...Hybrid quantum system of negatively charged nitrogen–vacancy(NV^-) centers in diamond and superconducting qubits provide the possibility to extend the performances of both systems. In this work, we numerically simulate the coupling strength between NV^-ensembles and superconducting flux qubits and obtain a lower bound of 1016cm^(-3) for NV^-concentration to achieve a sufficiently strong coupling of 10 MHz when the gap between NV^-ensemble and flux qubit is 0. Moreover, we create NV^-ensembles in different types of diamonds by14^(N+)and12(C+)ion implantation, electron irradiation, and high temperature annealing. We obtain an NV^-concentration of 1.05 × 1016cm^(-3) in the diamond with1-ppm nitrogen impurity, which is expected to have a long coherence time for the low nitrogen impurity concentration. This shows a step toward performance improvement of flux qubit-NV^-hybrid system.展开更多
Background Patients with Parkinson’s disease(PD)undergoing long-term levodopa therapy are prone to develop levodopa-induced dyskinesia(LID).Amantadine is the main drug recommended for the treatment of LID by current ...Background Patients with Parkinson’s disease(PD)undergoing long-term levodopa therapy are prone to develop levodopa-induced dyskinesia(LID).Amantadine is the main drug recommended for the treatment of LID by current guidelines,but it is far from meeting clinical needs.Tianqi Pingchan Granule(TPG),a compound Chinese herbal medicine,has been developed to relieve symptom of LID.Objective This randomized controlled trial evaluated the efficacy and safety of the combination of TPG and amantadine for LID.Design,setting,participants and interventions This is a randomized double-blind placebo-controlled trial,conducted from January 2020 to August 2021 at 6 sites in Jiangsu,Zhejiang and Shanghai,China.One hundred PD patients with≥0.5 h of LID were randomly assigned to either the TPG plus amantadine group(TPG group)or the placebo plus amantadine group(placebo group),and treated for a period of 12 weeks.To ensure unbiased results,all study participants,investigators and sponsors were unaware of group allocations.Additionally,the data analysts remained blinded until the analysis was finalized.Main outcome measures The primary outcome was assessed using the Unified Dyskinesia Rating Scale(UDysRS)(Range 0–104).The key secondary end point was improvement of motor and non-motor symptoms.Safety analyses included all enrolled patients.Results One hundred patients were enrolled and randomized into the two treatment groups.The changes in UDysRS at week 12 were–11.02 for the TPG group and–4.19 for the placebo group(treatment difference–6.83[–10.53 to–3.12];P=0.0004).Adverse events were reported for 2 of 50 patients(4.0%)in each of the groups.Conclusion This study indicated that a 12-week treatment of amantadine plus TPG effectively reduced UDysRS scores and was well tolerated,demonstrating the efficacy and safety of TPG for the treatment of LID in PD.展开更多
基金the National Science Foundation of China(Nos.50934001 and 51322402)the National High-Tech Research and Development Program of China (No.2012AA062302)+2 种基金the Program of the Co-construction with Beijing Municipal Commission of Education of China (Nos.00012047 and 00012085)the Program for New Century Excellent Talents in Universities(NCET-11-0577)the Fundamental Research Funds for the Central Universities(No.FRF-AS-11-003A)
文摘TiClx (x=2.17) was prepared by using titanium sponge to reduce the concentration of TiCl4 in a NaCl-KCl melt under negative pressure. The as-prepared NaCl-KCl-TiClx melt was employed as the electrolyte, and two parallel crude titanium plates and one high-purity titanium plate were used as the anode and cathode, respectively. A series of electrochemical tests were performed to investigate the influence of electrolytic parameters on the current efficiency and quality of cathodic products. The results indicated that the quality of cathodic products was related to the current efficiency, which is significantly dependent on the current density and the initial concentration of titanium ions. The significance of this study is the attainment of high-purity titanium with a low oxygen content of 30× 10^-6.
文摘AIM:To explore the influencing factors of diabetes type 2 patients with mild non-proliferative diabetic retinopathy(NPDR)in the Kailuan area of Tangshan,Hebei Province,China.METHODS:In this non-interventional,retrospective study,683 patients with type 2 diabetes were included in the Kailuan Diabetic Retinopathy Study involving participants with diabetes in the community-based longitudinal Kailuan Study.Based on the undilated ultrawide field(200°;UWF)images and partial dilated digital fundus images,the diabetic retinopathy(DR)of the surveyed population was graded.Interobserver agreement was estimated by using Cohen’s Kappa statistics.The main outcome indicators included gender,age,weight,height,body mass index,blood pressure,circumferences of neck,waist and hip,current smoking,levels of fasting plasma glucose(FPG),hypersensitive C-reactive protein,creatinine,and cholesterol,etc.According to different lesions’locations of patients with mild NPDR,logistic regression models were used to estimate the odds ratios(ORs)and their 95%Cls of each risk factor.RESULTS:The study group of 683 patients included 570 males and 113 females.The mean age of the patients was62.18±9.41 y.Compared with dilated fundus examinations,there was fair agreement with the level of DR identified on UWF images in 63.91%of eyes(k=0.369,95%CI,0.00-0.00).Detected by UWF images,there were 98 patients with mild NPDR having peripheral retinal lesions,35 patients with mild NPDR having posterior lesions,44 patients with mild NPDR whose lesions were detected both in and out the standard two fields area,and 336 patients with non obvious DR.Parameters that conferred a statistically significant increased risks for mild NPDR with having peripheral retinal lesions were neck circumstance(OR,1.124;95%CI,1.044-1.211),and with posterior lesions were FPG(OR,1.052;95%CI,1.007-1.099).CONCLUSION:UWF is an effectiveness means of DR screening.Moreover,it is necessary to evaluate peripheral diabetic retinal lesions which can help to estimate the severity of DR.The phenomenon that nonuniform and inhomogeneous distribution of DR lesions has been found.And the influencing factors in mild NPDR are differing by different lesions’locations.
基金Supported by National Natural Science Foundation of China(No.81271012)
文摘AIM: To examine the expression of Twik-related K+ channel 1(TREK-1), Twik-related K+ channel 2(TREK-2), and Twik-related arachidonic acid-stimulated K+ channel(TRAAK) in the retina of adult rd1 mice and to detect the protective roles of TREK-TRAAK two-pore-domain K+(K2P) channels against retinal degeneration.METHODS: Twenty-eight-day-old C57BL/6J mice and 28-day-old rd1 mice were used in this study. Retinal protein, retinal RNA, and embedded eyeballs were prepared from these two groups of mice. Real-time quantitative polymerase chain reaction and Western blot analyses were used to assess the gene transcription and protein levels, respectively. Retinal structures were observed using hematoxylin and eosin(H&E) staining. Immunohistochemistry was utilized to observe the retinal localization of TREK-TRAAK channels. Current changes in retinal ganglion cells(RGCs) after activation of TREK-TRAAK channels were examined using a patchclamp technique. RESULTS: Compared with C57BL/6J mice, rd1 mice exhibited significantly higher retinal mRNA and protein expression levels of TREK-1, TREK-2, and TRAAK channels. In both groups, immunohistochemistry showed expression of TREK-TRAAK channels in retinal layers. After addition of the TREK-TRAAK channel agonist arachidonic acid(AA), whole-cell voltage step evoked currents were significantly higher in RGCs from rd1 mice than in RGCs from control C57BL/6J mice, suggesting that TREK-TRAAK channels were opened in RGCs from rd1 mice. CONCLUSION: TREK-TRAAK K2P channels’ expression is increased in adult rd1 mice. AA induced the opening of TREK-TRAAK K2P channels in adult rd1 mice and may thus counterbalance depolarization of RGCs and protect the retina from excitotoxicity. TREK-TRAAK channels may play a protective role against retinal degeneration.
基金Guangdong Natural Science Foundation (No.2016A030313344)。
文摘AIM: To observe and compare the statistical significance of superficial and deep vascular leakage in the pathological changes of the diabetic rats retina after the Evans blue(EB) perfusion, and utilize the modified whole-retina spreading method to make the slides while protecting the periphery of the retina. METHODS: The Sprague-Dawley(SD) rats were randomly divided into 6 groups. Each group named as the normal groups for 4, 8, and 12 wk and the diabetic groups for 4, 8, and 12 wk. The EB was injected into the cardiovascular system of the rats at the different time points. The retina of each group was obtained for observation.RESULTS: The superficial vascular leakage was found in all 6 groups. The size of leakage area of superficial retinal blood vessels was(0.54±0.23)%,(0.65±0.11)%,and(0.58±0.10)% in normal group. No notable leakage was found in the deep blood vessels [(0.03±0.04)%,(0.03±0.05)%, and(0.03±0.05)%]. The deep retinal vascular leakage was found in the peripheral retina of diabetic rats. The size of leakage area of superficial retinal blood vessels in diabetic group were(0.53±0.22)%,(0.69±0.16)%, and(0.52±0.11)%. The leakage areas of deep blood vessels were(0.54±0.50)%,(1.42±0.16)%, and(1.80±0.07)% at 4, 8, and 12 wk, respectively. There was a statistically difference of the leakage area between the 8 th week and the 4 th week of diabetes group(P=0.003). The statistically significant difference between the diabetes and the control groups was noted at 4 wk and 8 wk(P<0.001).CONCLUSION: The main retinal pathological changes of early-stage diabetic rats are the vascular leakage of the periphery of deep retina. Diabetic rats modeled after 8 wk have semi-quantitative statistical difference compared with the normal rats, thus early intervention treatment research can start at this time point.
基金Supported by National Natural Science Foundation of China (No.81271012)
文摘AIM: To investigate the expression of TWIK-related arachidonic acid-stimulated K+ channel(TRAAK) in retinal degeneration mice(rd1) and further evaluate how TRAAK affect photoreceptor cell apoptosis.METHODS: The rd1 mice were distributed into blank(no treatment), control(1.4% DMSO, intraperitoneal injection) and riluzole groups(4 mg/kg·d, intraperitoneal injection) from postnatal 7 d to 10, 14 and 18 d;C57 group(no treatment), as age-matched wild-type control. The thickness of the outer nuclear layer(ONL) of retina was detected by paraffin section hematoxylin and eosin staining. The expression of TRAAK and the apoptosis of the ONL cells were detected by immunostaining, Western blotting, and real-time polymerase chain reaction. RESULTS: The channel agonist riluzole activated TRAAK and delayed the apoptosis of photoreceptor cells in ONL layer of rd1 mice. Both at mRNA and protein levels, after riluzole treatment, TRAAK expression was significantly upregulated, when compared with the control and blank group. Then we detected a series of apoptosis related mRNA and protein. The anti-apoptotic factor Bcl-2 downregulated and the pro-apoptotic factors Bax and cleaved-caspase-3 upregulated significantly. CONCLUSION: Riluzole elevates the expression of TRAAK and inhibits the development of apoptosis. Activation of TRAAK may have some potential effects to put off photoreceptor apoptosis.
文摘BACKGROUND Oxidized low-density lipoprotein(ox-LDL),which is abnormally increased in the serum of colorectal cancer(CRC)patients consuming a high-fat diet(HFD),may be one of the risk factors for the development of CRC.Ox-LDL exerts a regulatory effect on macrophages and may influence CRC through the tumor microenvironment.The role of ox-LDL in CRC remains unclear.AIM To investigate the role of ox-LDL through macrophages in HFD associated CRC.METHODS The expression of ox-LDL and CD206 was detected in colorectal tissues of CRC patients with hyperlipidemia and HFD-fed mice by immunofluorescence.We stimulated the macrophages with 20μg/mL ox-LDL and assessed the expression levels of CD206 and the cytokines by cell fluorescence and quantitative polymerase chain reaction.We further knocked down LOX-1,the surface receptor of ox-LDL,to confirm the function of ox-LDL in macrophages.Then,LoVo cells were co-cultured with the stimulated macrophages to analyze the CD44 and CD133 expression by western blot.RESULTS The expression of ox-LDL and the CD206 was significantly increased in the stroma of colorectal tissues of CRC patients with hyperlipidemia,and also upregulated in the HFD-fed mice.Moreover,an increased level of CD206 and decreased level of inducible nitric oxide synthase were observed in macrophages after ox-LDL continuous stimulation.Such effects were inhibited when the surface receptor LOX-1 was knocked down in macrophages.Ox-LDL could induce CD206+macrophages,which resulted in high expression of CD44 and CD133 in co-cultured LoVo cells.CONCLUSION Ox-LDL stimulates CD206+macrophages to upregulate CD44 and CD133 expression in HFD related CRC.
基金Project supported in part by the National Natural Science Foundation of China(Grant Nos.91321208,11574386,11374344,and 11574380)the National Basic Research Program of China(Grant Nos.2014CB921401 and 2016YFA0300601)the Strategic Priority Research Program of the Chinese Academy of Sciences(Grant No.XDB07010300)
文摘Hybrid quantum system of negatively charged nitrogen–vacancy(NV^-) centers in diamond and superconducting qubits provide the possibility to extend the performances of both systems. In this work, we numerically simulate the coupling strength between NV^-ensembles and superconducting flux qubits and obtain a lower bound of 1016cm^(-3) for NV^-concentration to achieve a sufficiently strong coupling of 10 MHz when the gap between NV^-ensemble and flux qubit is 0. Moreover, we create NV^-ensembles in different types of diamonds by14^(N+)and12(C+)ion implantation, electron irradiation, and high temperature annealing. We obtain an NV^-concentration of 1.05 × 1016cm^(-3) in the diamond with1-ppm nitrogen impurity, which is expected to have a long coherence time for the low nitrogen impurity concentration. This shows a step toward performance improvement of flux qubit-NV^-hybrid system.
基金supported by the National Key R&D Program of China(No.2017YFC1310300)National Natural Science Foundation of China(No.81974173,82171242)Pilot Project of Clinical Cooperation Between Chinese and Western Medicine in Shanghai(No.ZXYXZ-201907).
文摘Background Patients with Parkinson’s disease(PD)undergoing long-term levodopa therapy are prone to develop levodopa-induced dyskinesia(LID).Amantadine is the main drug recommended for the treatment of LID by current guidelines,but it is far from meeting clinical needs.Tianqi Pingchan Granule(TPG),a compound Chinese herbal medicine,has been developed to relieve symptom of LID.Objective This randomized controlled trial evaluated the efficacy and safety of the combination of TPG and amantadine for LID.Design,setting,participants and interventions This is a randomized double-blind placebo-controlled trial,conducted from January 2020 to August 2021 at 6 sites in Jiangsu,Zhejiang and Shanghai,China.One hundred PD patients with≥0.5 h of LID were randomly assigned to either the TPG plus amantadine group(TPG group)or the placebo plus amantadine group(placebo group),and treated for a period of 12 weeks.To ensure unbiased results,all study participants,investigators and sponsors were unaware of group allocations.Additionally,the data analysts remained blinded until the analysis was finalized.Main outcome measures The primary outcome was assessed using the Unified Dyskinesia Rating Scale(UDysRS)(Range 0–104).The key secondary end point was improvement of motor and non-motor symptoms.Safety analyses included all enrolled patients.Results One hundred patients were enrolled and randomized into the two treatment groups.The changes in UDysRS at week 12 were–11.02 for the TPG group and–4.19 for the placebo group(treatment difference–6.83[–10.53 to–3.12];P=0.0004).Adverse events were reported for 2 of 50 patients(4.0%)in each of the groups.Conclusion This study indicated that a 12-week treatment of amantadine plus TPG effectively reduced UDysRS scores and was well tolerated,demonstrating the efficacy and safety of TPG for the treatment of LID in PD.