Skeletal muscle atrophy results from disruptions in the growth and metabolism of striated muscle,leading to a reduction or loss of muscle fibers.This condition not only significantly impacts patients’quality of life ...Skeletal muscle atrophy results from disruptions in the growth and metabolism of striated muscle,leading to a reduction or loss of muscle fibers.This condition not only significantly impacts patients’quality of life but also imposes substantial socioeconomic burdens.The complex molecular mechanisms driving skeletal muscle atrophy contribute to the absence of effective treatment options.Recent advances in stem cell therapy have positioned it as a promising approach for addressing this condition.This article reviews the molecular mechanisms of muscle atrophy and outlines current therapeutic strategies,focusing on mesenchymal stem cells,induced pluripotent stem cells,and their derivatives.Additionally,the challenges these stem cells face in clinical applications are discussed.A deeper understanding of the regenerative potential of various stem cells could pave the way for breakthroughs in the prevention and treatment of muscle atrophy.展开更多
AIMTo report the appearance of choriocapillaris atrophy after combined high dose intravitreal triamcinolone acetonide (TA) and photodynamic therapy (PDT) to treat choroidal neovascularization (CNV) associated with age...AIMTo report the appearance of choriocapillaris atrophy after combined high dose intravitreal triamcinolone acetonide (TA) and photodynamic therapy (PDT) to treat choroidal neovascularization (CNV) associated with age related macular degeneration (AMD).展开更多
Spinal muscular atrophy is a devastating motor neuron disease characterized by severe cases of fatal muscle weakness.It is one of the most common genetic causes of mortality among infants aged less than 2 years.Biomar...Spinal muscular atrophy is a devastating motor neuron disease characterized by severe cases of fatal muscle weakness.It is one of the most common genetic causes of mortality among infants aged less than 2 years.Biomarker research is currently receiving more attention,and new candidate biomarkers are constantly being discovered.This review initially discusses the evaluation methods commonly used in clinical practice while briefly outlining their respective pros and cons.We also describe recent advancements in research and the clinical significance of molecular biomarkers for spinal muscular atrophy,which are classified as either specific or non-specific biomarkers.This review provides new insights into the pathogenesis of spinal muscular atrophy,the mechanism of biomarkers in response to drug-modified therapies,the selection of biomarker candidates,and would promote the development of future research.Furthermore,the successful utilization of biomarkers may facilitate the implementation of gene-targeting treatments for patients with spinal muscular atrophy.展开更多
BACKGROUND Intramuscular corticosteroid injection may cause adverse effects such as dermal and/or subcutaneous atrophy,alopecia,hypopigmentation,and hyperpigmentation.Although cutaneous atrophy can spontaneously resol...BACKGROUND Intramuscular corticosteroid injection may cause adverse effects such as dermal and/or subcutaneous atrophy,alopecia,hypopigmentation,and hyperpigmentation.Although cutaneous atrophy can spontaneously resolve,several treatment options have been suggested for this condition.CASE SUMMARY In this paper,we report a case of corticosteroid injection induced lipoatrophy treated with autologous whole blood(AWB)injection,as the condition had been unresponsive to fractional laser therapy.A 29-year-old female patient visited the dermatology clinic complaining of skin depression on her right buttock area,which had appeared six months earlier.There had been only subtle improvement at the margins after fractional CO_(2) laser treatment;therefore,after obtaining informed consent from the patient,AWB treatment was initiated.One month after the first AWB injection,the size and depth of the lesion had noticeably improved,and a slight improvement was also observed in discoloration.CONCLUSION Close observation is the initial treatment of choice for steroid induced skin atrophy;however,for patients in need of immediate cosmetic improvement,AWB injection may be a safe and cost-effective alternative.展开更多
Common neurodegenerative diseases of the central nervous system are characterized by progressive damage to the function of neurons, even leading to the permanent loss of function. Gene therapy via gene replacement or ...Common neurodegenerative diseases of the central nervous system are characterized by progressive damage to the function of neurons, even leading to the permanent loss of function. Gene therapy via gene replacement or gene correction provides the potential for transformative therapies to delay or possibly stop further progression of the neurodegenerative disease in affected patients. Adeno-associated virus has been the vector of choice in recent clinical trials of therapies for neurodegenerative diseases due to its safety and efficiency in mediating gene transfer to the central nervous system. This review aims to discuss and summarize the progress and clinical applications of adeno-associated virus in neurodegenerative disease in central nervous system. Results from some clinical trials and successful cases of central neurodegenerative diseases deserve further study and exploration.展开更多
Background:A high prevalence of diabetes mellitus(DM)coexisting with autoimmune pancreatitis(AIP)is observed.However,evidence on the circumstances under which corticosteroid therapy(CST)for AIP improves or worsens DM ...Background:A high prevalence of diabetes mellitus(DM)coexisting with autoimmune pancreatitis(AIP)is observed.However,evidence on the circumstances under which corticosteroid therapy(CST)for AIP improves or worsens DM is scarce.This study aimed to demonstrate and identify predictors of DM control under the influence of CST.Methods:Patients diagnosed with type 1 AIP were enrolled from a prospectively maintained cohort and were classified into three groups according to the chronology in which AIP and DM were diagnosed:pre-existing DM(pDM),concurrent DM(cDM),and non-DM(nDM).The responses of DM to CST were assessed when corticosteroid was ceased or tapered to a maintenance dose and classified as‘improvement’and‘non-improvement’(including‘no change’and‘exacerbation’).Results:Among 101 patients with type 1 AIP,52(51.5%)patients were complicated with DM at the time of AIP diagnosis,with 36 patients in the cDM group and 16 patients in the pDM group.The incidences of diffuse pancreatic swelling(72.2%)and pancreatic body/tail involvement(91.7%)were significantly higher in the cDM group than in both the pDM and nDM groups.Of the 52 patients with DM,CST was administered in 48 cases.Multivariate logistic analysis identified that elevated serum gamma-glutamyl transferase(GGT)level at AIP diagnosis[odds ratio(OR)=0.032,95%confidence interval(CI):0.003-0.412,P=0.008]and pancreatic atrophy after CST(OR=0.027,95%CI:0.003-0.295,P=0.003)were negatively associated with DM control improvement.Conclusions:Patients with diffuse pancreatic swelling and pancreatic body/tail involvement in pancreatitis tended to be complicated with cDM at AIP diagnosis.CST exerted a beneficial effect on the clinical course of DM in nearly half of the AIP patients complicated with DM at diagnosis,particularly in those without elevated serum GGT levels at diagnosis and who did not experience pancreatic atrophy after CST.展开更多
OBJECTIVE： To evaluate the efficacy and safety of acupuncture for optic atrophy. DATA SOURCES： A computer-based online search was conducted in Medline （1966-2008）, Embase （1986-2008）, the Cochrane Library （up t...OBJECTIVE： To evaluate the efficacy and safety of acupuncture for optic atrophy. DATA SOURCES： A computer-based online search was conducted in Medline （1966-2008）, Embase （1986-2008）, the Cochrane Library （up to 2008）, Chinese Biomedical Literature Database （1975-2008）, China National Knowledge Infrastructure （1994-2008）, VIP Database （1989-2008）, Wanfang Database （1980-2008） and the National Research Register for ongoing trials. DATA SELECTION： Randomized, controlled trials addressing acupuncture treatment for patients with optic atrophy were included in this review. Inclusion criteria evaluated all forms of acupuncture therapy, such as filiform needle, electro-acupuncture, laser-acupuncture, acupressure, and auricular-acupuncture. Comparisons between acupuncture therapy and no treatment （blank） or placebo or Chinese medicine or Western medicine, as well as between acupuncture as an adjuvant and other treatments, were included. Exclusion criteria included studies comparing different forms of acupuncture therapy, different manipulations of acupuncture, and different acupuncture prescriptions, as well as non-randomized, controlled trials and animal studies. The domain-based evaluation criteria recommended by the guidelines in Chapter 8 of the Cochrane Handbook for Systematic Reviews of Interventions 5.0.1 was used to assess quality of the included studies. According to the type of outcome index, measurement data as assessed by weighted mean difference or standardized mean difference and 95% confidence interval; numeration data was estimated by relative risk and 95% confidence interval. Heterogeneity was analyzed by Meta-analysis using RevMan 5.0 software. MAIN OUTCOME MEASURES： Improved visual acuity and visual field was sought between treatment and control groups in the included articles. RESULTS： Seven randomized, controlled trials were included after screening and application of inclusion and exclusion criteria. However, the studies were of low methodological quality and lacked comparisons between acupuncture and no treatment or placebo. Applying visual acuity as the outcome index, meta-analysis indicated： the effect of medicine combined with acupuncture was superior to the medicine alone （relative risk = 1.41, 95% confidence interval 1.14-1.70, P 〈 0.01 ）, the efficacy of acupuncture was better than medicine alone （relative risk =1.42, 95% confidence interval 1.14-1.77, P 〈 0.01 ）. Using visual field as the other outcome index, meta-analysis revealed： effectiveness of acupuncture or acupuncture in combination with medicine was superior to medicine alone （relative risk = 1.47, 95% confidence interval 1.27-1.69, P 〈 0.01 ）. The 7 included articles were incorporated in a sensitivity analysis, and the overall effect showed a significant difference （relative risk = 1.35, 95% confidence interval 1.16-1.56, P 〈 0.01）. Acupuncture was not associated with any adverse events in any of the studies. CONCLUSION： Acupuncture therapy was determined to be superior to medicine in terms of improved visual acuity and visual field. However, well-designed, randomized, controlled trials with adequate controls and scientific rigor are urgently needed.展开更多
Optic atrophy results mostly from affection by exopathic wind pathogen, insufficiency of Qi and Xue(blood) or hyperactivity of the liver-yang. We choose Qiuhou(EX-HN 7), Jingming(BL1 ), Taiyang(EX-HN 5 ) and Fengchi(G...Optic atrophy results mostly from affection by exopathic wind pathogen, insufficiency of Qi and Xue(blood) or hyperactivity of the liver-yang. We choose Qiuhou(EX-HN 7), Jingming(BL1 ), Taiyang(EX-HN 5 ) and Fengchi(GB 20) as the main acupoints and combine other auxiliary points according to different syndromes. For example, Hegu(LI 4) and Waiguan(TE 5 ) are supplemented for affection by exopathic wind pathogen, Qihai(CV 6), Zusanli(ST 36), Xuehai(SP 10) and Guang-ming(GB 37) for insufficiency of Qi and Xue, and Guanshu(BL 18), Baihui(GV 20), Taixi(KI 3),Sanyinjiao(SP 6) and Guangming(GB 37) for hyperactivity of the liveryang. When Qiuhou(EX-HN 7), Jingming(BL 1 ) and Fenchi(GB 20) punctured, the need1ing direction, angle and depth should be controlled very appropriate for achieving good therapeutic effect.展开更多
48 cases of optic atrophy were treated with acupuncture. Qiuhou (EX-HN 7), Jing-ming (BL 1), Ganshu (BL 18), Pishu (BL 20), Fengchi (GB 20), Cuanzhu (BL 2), Yiming (EX-HN 14), Guangming (GB 37), Taiyang (EX-HN 5), Yan...48 cases of optic atrophy were treated with acupuncture. Qiuhou (EX-HN 7), Jing-ming (BL 1), Ganshu (BL 18), Pishu (BL 20), Fengchi (GB 20), Cuanzhu (BL 2), Yiming (EX-HN 14), Guangming (GB 37), Taiyang (EX-HN 5), Yanglao (SI 6), Sibai (ST 2), Tongziliao(GB 1) were selected as main points, of which three to five points were punctured each time, but thefirst two were used necessarily. According to an overall differentiation of symptoms and signs auxiliarypoints were supplemented. The treatment was given once everyday with the manipulations of twirlingneedles plus slow or rapid insertion for reinforcing or reducing to make the needling sensation reach theeye regions. Twelve treatments made a course with an interval of 3 days between the two courses. Itwas shown that 15 cases were markedly effective (3l. 25 % ), 26 improved (54. 17% ), and 7 ineffec-tive (14. 58 % ). The total effective rate was 85.42%.展开更多
The author punctured Kuangshang (the medial one third of the supraorbitalmargin ), Jieli (midway between the occipital condyle and apex helix) and Yintang ((EX-HN3 ) asmain points to treat optic atrophy in 164 eyes of...The author punctured Kuangshang (the medial one third of the supraorbitalmargin ), Jieli (midway between the occipital condyle and apex helix) and Yintang ((EX-HN3 ) asmain points to treat optic atrophy in 164 eyes of 110 patients. The results showed that 12 eyes (7.3% ) were cured, 71 eyes (43. 3 % ) remarkably effective, 39 eyes (23. 8 % ) improved and 42 eyes(25. 6 % ) ineffective, with the total effective rate 74. 4 %.展开更多
Does anti-vascular endothelial growth factor(VEGF)therapy lead to geographic atrophy?If so,does the number of injections or the duration of anti-VEGF therapy correlate with the risk of developing geographic atrophy?Wi...Does anti-vascular endothelial growth factor(VEGF)therapy lead to geographic atrophy?If so,does the number of injections or the duration of anti-VEGF therapy correlate with the risk of developing geographic atrophy?With intravitreal injections becoming the most common ophthalmic invasive procedure and an increasingly aging population,these questions really matter.展开更多
基金Suzhou Science and Technology Development Planning Project,No.SYW2024048National Natural Science Foundation of China,No.81901933Major Natural Science Research Projects in Universities of Jiangsu Province,No.24KJA310007.
文摘Skeletal muscle atrophy results from disruptions in the growth and metabolism of striated muscle,leading to a reduction or loss of muscle fibers.This condition not only significantly impacts patients’quality of life but also imposes substantial socioeconomic burdens.The complex molecular mechanisms driving skeletal muscle atrophy contribute to the absence of effective treatment options.Recent advances in stem cell therapy have positioned it as a promising approach for addressing this condition.This article reviews the molecular mechanisms of muscle atrophy and outlines current therapeutic strategies,focusing on mesenchymal stem cells,induced pluripotent stem cells,and their derivatives.Additionally,the challenges these stem cells face in clinical applications are discussed.A deeper understanding of the regenerative potential of various stem cells could pave the way for breakthroughs in the prevention and treatment of muscle atrophy.
文摘AIMTo report the appearance of choriocapillaris atrophy after combined high dose intravitreal triamcinolone acetonide (TA) and photodynamic therapy (PDT) to treat choroidal neovascularization (CNV) associated with age related macular degeneration (AMD).
基金supported by the Collaborative Innovation Center for Clinical and Translational Science by Chinese Ministry of Education&Shanghai,No.CCTS-2022205the“Double World-Class Project”of Shanghai Jiaotong University School of Medicine(both to JZ)。
文摘Spinal muscular atrophy is a devastating motor neuron disease characterized by severe cases of fatal muscle weakness.It is one of the most common genetic causes of mortality among infants aged less than 2 years.Biomarker research is currently receiving more attention,and new candidate biomarkers are constantly being discovered.This review initially discusses the evaluation methods commonly used in clinical practice while briefly outlining their respective pros and cons.We also describe recent advancements in research and the clinical significance of molecular biomarkers for spinal muscular atrophy,which are classified as either specific or non-specific biomarkers.This review provides new insights into the pathogenesis of spinal muscular atrophy,the mechanism of biomarkers in response to drug-modified therapies,the selection of biomarker candidates,and would promote the development of future research.Furthermore,the successful utilization of biomarkers may facilitate the implementation of gene-targeting treatments for patients with spinal muscular atrophy.
基金Supported by The New Faculty Research Grant of Pusan National University,2023The Research Grant of the Chungbuk National University in 2023.
文摘BACKGROUND Intramuscular corticosteroid injection may cause adverse effects such as dermal and/or subcutaneous atrophy,alopecia,hypopigmentation,and hyperpigmentation.Although cutaneous atrophy can spontaneously resolve,several treatment options have been suggested for this condition.CASE SUMMARY In this paper,we report a case of corticosteroid injection induced lipoatrophy treated with autologous whole blood(AWB)injection,as the condition had been unresponsive to fractional laser therapy.A 29-year-old female patient visited the dermatology clinic complaining of skin depression on her right buttock area,which had appeared six months earlier.There had been only subtle improvement at the margins after fractional CO_(2) laser treatment;therefore,after obtaining informed consent from the patient,AWB treatment was initiated.One month after the first AWB injection,the size and depth of the lesion had noticeably improved,and a slight improvement was also observed in discoloration.CONCLUSION Close observation is the initial treatment of choice for steroid induced skin atrophy;however,for patients in need of immediate cosmetic improvement,AWB injection may be a safe and cost-effective alternative.
文摘Common neurodegenerative diseases of the central nervous system are characterized by progressive damage to the function of neurons, even leading to the permanent loss of function. Gene therapy via gene replacement or gene correction provides the potential for transformative therapies to delay or possibly stop further progression of the neurodegenerative disease in affected patients. Adeno-associated virus has been the vector of choice in recent clinical trials of therapies for neurodegenerative diseases due to its safety and efficiency in mediating gene transfer to the central nervous system. This review aims to discuss and summarize the progress and clinical applications of adeno-associated virus in neurodegenerative disease in central nervous system. Results from some clinical trials and successful cases of central neurodegenerative diseases deserve further study and exploration.
基金from CAMS Innovation Fund for Medical Sciences(CIFMS)(2021-I2M-1-002)National Key Clinical Specialty Construction Project(ZK108000)+1 种基金National High-Level Hospital Clinical Research Funding(2022-PUMCH-B-024)National Natural Science Foundation of China,Joint Fund Project(U20A600).
文摘Background:A high prevalence of diabetes mellitus(DM)coexisting with autoimmune pancreatitis(AIP)is observed.However,evidence on the circumstances under which corticosteroid therapy(CST)for AIP improves or worsens DM is scarce.This study aimed to demonstrate and identify predictors of DM control under the influence of CST.Methods:Patients diagnosed with type 1 AIP were enrolled from a prospectively maintained cohort and were classified into three groups according to the chronology in which AIP and DM were diagnosed:pre-existing DM(pDM),concurrent DM(cDM),and non-DM(nDM).The responses of DM to CST were assessed when corticosteroid was ceased or tapered to a maintenance dose and classified as‘improvement’and‘non-improvement’(including‘no change’and‘exacerbation’).Results:Among 101 patients with type 1 AIP,52(51.5%)patients were complicated with DM at the time of AIP diagnosis,with 36 patients in the cDM group and 16 patients in the pDM group.The incidences of diffuse pancreatic swelling(72.2%)and pancreatic body/tail involvement(91.7%)were significantly higher in the cDM group than in both the pDM and nDM groups.Of the 52 patients with DM,CST was administered in 48 cases.Multivariate logistic analysis identified that elevated serum gamma-glutamyl transferase(GGT)level at AIP diagnosis[odds ratio(OR)=0.032,95%confidence interval(CI):0.003-0.412,P=0.008]and pancreatic atrophy after CST(OR=0.027,95%CI:0.003-0.295,P=0.003)were negatively associated with DM control improvement.Conclusions:Patients with diffuse pancreatic swelling and pancreatic body/tail involvement in pancreatitis tended to be complicated with cDM at AIP diagnosis.CST exerted a beneficial effect on the clinical course of DM in nearly half of the AIP patients complicated with DM at diagnosis,particularly in those without elevated serum GGT levels at diagnosis and who did not experience pancreatic atrophy after CST.
基金Supported by: the National Key Basic ResearchDevelopment Plan Program of China, No. 2006CB504501
文摘OBJECTIVE： To evaluate the efficacy and safety of acupuncture for optic atrophy. DATA SOURCES： A computer-based online search was conducted in Medline （1966-2008）, Embase （1986-2008）, the Cochrane Library （up to 2008）, Chinese Biomedical Literature Database （1975-2008）, China National Knowledge Infrastructure （1994-2008）, VIP Database （1989-2008）, Wanfang Database （1980-2008） and the National Research Register for ongoing trials. DATA SELECTION： Randomized, controlled trials addressing acupuncture treatment for patients with optic atrophy were included in this review. Inclusion criteria evaluated all forms of acupuncture therapy, such as filiform needle, electro-acupuncture, laser-acupuncture, acupressure, and auricular-acupuncture. Comparisons between acupuncture therapy and no treatment （blank） or placebo or Chinese medicine or Western medicine, as well as between acupuncture as an adjuvant and other treatments, were included. Exclusion criteria included studies comparing different forms of acupuncture therapy, different manipulations of acupuncture, and different acupuncture prescriptions, as well as non-randomized, controlled trials and animal studies. The domain-based evaluation criteria recommended by the guidelines in Chapter 8 of the Cochrane Handbook for Systematic Reviews of Interventions 5.0.1 was used to assess quality of the included studies. According to the type of outcome index, measurement data as assessed by weighted mean difference or standardized mean difference and 95% confidence interval; numeration data was estimated by relative risk and 95% confidence interval. Heterogeneity was analyzed by Meta-analysis using RevMan 5.0 software. MAIN OUTCOME MEASURES： Improved visual acuity and visual field was sought between treatment and control groups in the included articles. RESULTS： Seven randomized, controlled trials were included after screening and application of inclusion and exclusion criteria. However, the studies were of low methodological quality and lacked comparisons between acupuncture and no treatment or placebo. Applying visual acuity as the outcome index, meta-analysis indicated： the effect of medicine combined with acupuncture was superior to the medicine alone （relative risk = 1.41, 95% confidence interval 1.14-1.70, P 〈 0.01 ）, the efficacy of acupuncture was better than medicine alone （relative risk =1.42, 95% confidence interval 1.14-1.77, P 〈 0.01 ）. Using visual field as the other outcome index, meta-analysis revealed： effectiveness of acupuncture or acupuncture in combination with medicine was superior to medicine alone （relative risk = 1.47, 95% confidence interval 1.27-1.69, P 〈 0.01 ）. The 7 included articles were incorporated in a sensitivity analysis, and the overall effect showed a significant difference （relative risk = 1.35, 95% confidence interval 1.16-1.56, P 〈 0.01）. Acupuncture was not associated with any adverse events in any of the studies. CONCLUSION： Acupuncture therapy was determined to be superior to medicine in terms of improved visual acuity and visual field. However, well-designed, randomized, controlled trials with adequate controls and scientific rigor are urgently needed.
文摘Optic atrophy results mostly from affection by exopathic wind pathogen, insufficiency of Qi and Xue(blood) or hyperactivity of the liver-yang. We choose Qiuhou(EX-HN 7), Jingming(BL1 ), Taiyang(EX-HN 5 ) and Fengchi(GB 20) as the main acupoints and combine other auxiliary points according to different syndromes. For example, Hegu(LI 4) and Waiguan(TE 5 ) are supplemented for affection by exopathic wind pathogen, Qihai(CV 6), Zusanli(ST 36), Xuehai(SP 10) and Guang-ming(GB 37) for insufficiency of Qi and Xue, and Guanshu(BL 18), Baihui(GV 20), Taixi(KI 3),Sanyinjiao(SP 6) and Guangming(GB 37) for hyperactivity of the liveryang. When Qiuhou(EX-HN 7), Jingming(BL 1 ) and Fenchi(GB 20) punctured, the need1ing direction, angle and depth should be controlled very appropriate for achieving good therapeutic effect.
文摘48 cases of optic atrophy were treated with acupuncture. Qiuhou (EX-HN 7), Jing-ming (BL 1), Ganshu (BL 18), Pishu (BL 20), Fengchi (GB 20), Cuanzhu (BL 2), Yiming (EX-HN 14), Guangming (GB 37), Taiyang (EX-HN 5), Yanglao (SI 6), Sibai (ST 2), Tongziliao(GB 1) were selected as main points, of which three to five points were punctured each time, but thefirst two were used necessarily. According to an overall differentiation of symptoms and signs auxiliarypoints were supplemented. The treatment was given once everyday with the manipulations of twirlingneedles plus slow or rapid insertion for reinforcing or reducing to make the needling sensation reach theeye regions. Twelve treatments made a course with an interval of 3 days between the two courses. Itwas shown that 15 cases were markedly effective (3l. 25 % ), 26 improved (54. 17% ), and 7 ineffec-tive (14. 58 % ). The total effective rate was 85.42%.
文摘The author punctured Kuangshang (the medial one third of the supraorbitalmargin ), Jieli (midway between the occipital condyle and apex helix) and Yintang ((EX-HN3 ) asmain points to treat optic atrophy in 164 eyes of 110 patients. The results showed that 12 eyes (7.3% ) were cured, 71 eyes (43. 3 % ) remarkably effective, 39 eyes (23. 8 % ) improved and 42 eyes(25. 6 % ) ineffective, with the total effective rate 74. 4 %.
文摘Does anti-vascular endothelial growth factor(VEGF)therapy lead to geographic atrophy?If so,does the number of injections or the duration of anti-VEGF therapy correlate with the risk of developing geographic atrophy?With intravitreal injections becoming the most common ophthalmic invasive procedure and an increasingly aging population,these questions really matter.
