1.Safety, dosimetry, and efficacy of an optimized long-acting somatostatin analog for peptide receptor radionuclide therapy in metastatic neuroendocrine tumors: From preclinical testing to first-in-human study.
Wei GUO ; Xuejun WEN ; Yuhang CHEN ; Tianzhi ZHAO ; Jia LIU ; Yucen TAO ; Hao FU ; Hongjian WANG ; Weizhi XU ; Yizhen PANG ; Liang ZHAO ; Jingxiong HUANG ; Pengfei XU ; Zhide GUO ; Weibing MIAO ; Jingjing ZHANG ; Xiaoyuan CHEN ; Haojun CHEN
Acta Pharmaceutica Sinica B 2025;15(2):707-721
Peptide receptor radionuclide therapy (PRRT) with radiolabeled SSTR2 agonists is a treatment option that is highly effective in controlling metastatic and progressive neuroendocrine tumors (NETs). Previous studies have shown that an SSTR2 agonist combined with albumin binding moiety Evans blue (denoted as 177Lu-EB-TATE) is characterized by a higher tumor uptake and residence time in preclinical models and in patients with metastatic NETs. This study aimed to enhance the in vivo stability, pharmacokinetics, and pharmacodynamics of 177Lu-EB-TATE by replacing the maleimide-thiol group with a polyethylene glycol chain, resulting in a novel EB conjugated SSTR2-targeting radiopharmaceutical, 177Lu-LNC1010, for PRRT. In preclinical studies, 177Lu-LNC1010 exhibited good stability and SSTR2-binding affinity in AR42J tumor cells and enhanced uptake and prolonged retention in AR42J tumor xenografts. Thereafter, we presented the first-in-human dose escalation study of 177Lu-LNC1010 in patients with advanced/metastatic NETs. 177Lu-LNC1010 was well-tolerated by all patients, with minor adverse effects, and exhibited significant uptake and prolonged retention in tumor lesions, with higher tumor radiation doses than those of 177Lu-EB-TATE. Preliminary PRRT efficacy results showed an 83% disease control rate and a 42% overall response rate after two 177Lu-LNC1010 treatment cycles. These encouraging findings warrant further investigations through multicenter, prospective, and randomized controlled trials.
2.Expert consensus on the diagnosis and treatment of cemental tear.
Ye LIANG ; Hongrui LIU ; Chengjia XIE ; Yang YU ; Jinlong SHAO ; Chunxu LV ; Wenyan KANG ; Fuhua YAN ; Yaping PAN ; Faming CHEN ; Yan XU ; Zuomin WANG ; Yao SUN ; Ang LI ; Lili CHEN ; Qingxian LUAN ; Chuanjiang ZHAO ; Zhengguo CAO ; Yi LIU ; Jiang SUN ; Zhongchen SONG ; Lei ZHAO ; Li LIN ; Peihui DING ; Weilian SUN ; Jun WANG ; Jiang LIN ; Guangxun ZHU ; Qi ZHANG ; Lijun LUO ; Jiayin DENG ; Yihuai PAN ; Jin ZHAO ; Aimei SONG ; Hongmei GUO ; Jin ZHANG ; Pingping CUI ; Song GE ; Rui ZHANG ; Xiuyun REN ; Shengbin HUANG ; Xi WEI ; Lihong QIU ; Jing DENG ; Keqing PAN ; Dandan MA ; Hongyu ZHAO ; Dong CHEN ; Liangjun ZHONG ; Gang DING ; Wu CHEN ; Quanchen XU ; Xiaoyu SUN ; Lingqian DU ; Ling LI ; Yijia WANG ; Xiaoyuan LI ; Qiang CHEN ; Hui WANG ; Zheng ZHANG ; Mengmeng LIU ; Chengfei ZHANG ; Xuedong ZHOU ; Shaohua GE
International Journal of Oral Science 2025;17(1):61-61
Cemental tear is a rare and indetectable condition unless obvious clinical signs present with the involvement of surrounding periodontal and periapical tissues. Due to its clinical manifestations similar to common dental issues, such as vertical root fracture, primary endodontic diseases, and periodontal diseases, as well as the low awareness of cemental tear for clinicians, misdiagnosis often occurs. The critical principle for cemental tear treatment is to remove torn fragments, and overlooking fragments leads to futile therapy, which could deteriorate the conditions of the affected teeth. Therefore, accurate diagnosis and subsequent appropriate interventions are vital for managing cemental tear. Novel diagnostic tools, including cone-beam computed tomography (CBCT), microscopes, and enamel matrix derivatives, have improved early detection and management, enhancing tooth retention. The implementation of standardized diagnostic criteria and treatment protocols, combined with improved clinical awareness among dental professionals, serves to mitigate risks of diagnostic errors and suboptimal therapeutic interventions. This expert consensus reviewed the epidemiology, pathogenesis, potential predisposing factors, clinical manifestations, diagnosis, differential diagnosis, treatment, and prognosis of cemental tear, aiming to provide a clinical guideline and facilitate clinicians to have a better understanding of cemental tear.
Humans
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Dental Cementum/injuries*
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Consensus
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Diagnosis, Differential
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Cone-Beam Computed Tomography
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Tooth Fractures/therapy*
3.A Comparison Study Between Flexible Ureteroscopy and Non-retrograde Percutaneous Nephrolithotomy in the Treatment of 1.5-2.0 cm Upper Ureteral Stones
Guangyuan YANG ; Xiaosong SUN ; Dongcao LIU ; Xiaoyuan QIAN ; Fuchao LIANG ; Linghui QIN
Chinese Journal of Minimally Invasive Surgery 2025;25(8):480-484
Objective To compare the efficacy and safety of flexible ureteral lithotripsy(FURL)and non-retrograde percutaneous nephrolithotomy(NR-PCNL)for treating1.5-2.0 cm upper ureteral stones.Methods We retrospectively analyzed clinical data of 130 patients with upper ureteral stones treated between October 2022 and October 2024.Sixty-two patients underwent FURL and 68 underwent NR-PCNL.Comparisons included operative time,pre-and postoperative changes in white blood cells(WBC),hemoglobin(Hb),and creatinine(Cr),postoperative C-reactive protein(CRP)levels,stone-free rate after primary surgery,postoperative hospitalization duration,pain scores,complications,and need for auxiliary treatments.Results Compared to the FURL group,the NR-PCNL group demonstrated advantages in operative time[54.0(44.3,69.3)min vs.82.5(66.0,101.0)min,Z=-5.565,P<0.001],WBC elevation[1.9(0.5,3.5)×109/L vs.4.5(3.0,6.0)×109/L,Z=-4.528,P<0.001],and secondary surgery rate[0%(0/68)vs.14.5%(9/62),P<0.001].The FURL group showed lower Hb reduction[3.0(2.0,6.3)g/L vs.8.0(5.0,11.0)g/L,Z=-4.262,P<0.001],less postoperative Visual Analogue Scale(VAS)pain scores[1.0(1.0,2.0)points vs.2.0(1.0,2.0)points,Z=-2.840,P=0.005],and shorter hospitalization duration[2.0(1.0,2.0)d vs.3.0(2.0,3.0)d,Z=-5.815,P<0.001].No significant differences were observed in Cr elevation,CRP levels,stone-free rate after primary surgery,complications,or analgesic requirements(P≥0.05).Conclusions Both NR-PCNL and FURL are safe and effective for 1.5-2.0 cm upper ureteral stones.FURL offers better patient comfort,while NR-PCNL shows superior overall safety.
4.Clinical application effects of tissue flaps prepared from the discarded limbs after amputation in patients with destructive wounds in the lower limbs
Mitao HUANG ; Zhiyou HE ; Pihong ZHANG ; Minghua ZHANG ; Xu CUI ; Le GUO ; Xiaoyuan HUANG ; Pengfei LIANG
Chinese Journal of Burns 2025;41(1):77-83
Objective:To explore the clinical application effects of tissue flaps prepared from the discarded limbs after amputation in patients with destructive wounds in the lower limbs.Methods:The study was a retrospective observational study. From March 2019 to March 2024, 7 male patients with destructive wounds in the lower limbs who met the inclusion criteria were admitted to the Department of Burns and Plastic Surgery of Xiangya Hospital of Central South University, aged 35 to 57 years. After clinical treatment, the damaged limbs were still difficult to preserve. Five patients with destructive wounds in the lower limbs were repaired with pedicled tissue flaps prepared from the discarded limbs after amputation, with wound areas of 15 cm×10 cm to 25 cm×15 cm and tissue flap incision areas of 15 cm×10 cm to 20 cm×15 cm. Two patients with destructive wounds in the lower limbs were repaired with free tissue flaps prepared from the discarded limbs after amputation, with wound areas of 22 cm×18 cm and 25 cm×15 cm and tissue flap incision areas of 23 cm×20 cm and 25 cm×18 cm. The survival of the tissue flap, the healing and appearance of wounds in the recipient site were followed up. At the last follow-up, the recovery status of the recipient site was evaluated according to the comprehensive flap evaluation scale, and the status of corrective prosthesis fitting was recorded.Results:During the follow-up of 6 to 24 months, all the tissue flaps successfully survived, with good healing and appearance of wounds in the recipient site. At the last follow-up, the scores of the recovery status of the recipient site ranged from 36 to 39 (with an average of 37.2). All amputated limbs were able to accommodate corrective prostheses with no distal ulceration.Conclusions:Utilizing tissue flaps prepared from the discarded limbs after amputation in patients with destructive wounds in the lower limbs to repair wounds effectively uses the discarded tissue and avoid creating new donor sites, which is a method to be considered for repairing multiple destructive wounds.
5.Mechanisms by which microgravity causes osteoporosis
Dejian XIANG ; Xiaoyuan LIANG ; Shenghong WANG ; Changshun CHEN ; Cong TIAN ; Zhenxing YAN ; Bin GENG ; Yayi XIA
Chinese Journal of Tissue Engineering Research 2025;29(10):2132-2140
BACKGROUND:The imbalance between bone resorption and bone formation in microgravity environments leads to significant bone loss in astronauts.Current research indicates that bone loss under microgravity conditions is the result of the combined effects of various cells,tissues,and systems. OBJECTIVE:To review different biological effects of microgravity on various cells,tissues,or systems,and summarize the mechanisms by which microgravity leads to the development of osteoporosis. METHODS:Databases such as PubMed,Web of Science,and the Cochrane Database were searched for relevant literature from 2000 to 2023.The inclusion criteria were all articles related to tissue engineering studies and basic research on osteoporosis caused by microgravity.Ultimately,85 articles were included for review. RESULTS AND CONCLUSION:(1)In microgravity environment,bone marrow mesenchymal stem cells tend to differentiate more into adipocytes rather than osteoblasts,and hematopoietic stem cells in this environment are more inclined to differentiate into osteoclasts,reducing differentiation into the erythroid lineage.At the same time,microgravity inhibits the proliferation and differentiation of osteoblasts,promotes apoptosis of osteoblasts,alters cell morphology,and reduces the mineralization capacity of osteoblasts.Microgravity significantly increases the number and activity of osteoclasts.Microgravity also hinders the differentiation of osteoblasts into osteocytes and promotes the apoptosis of osteocytes.(2)In a microgravity environment,the body experiences changes such as skeletal muscle atrophy,microvascular remodeling,bone microcirculation disorders,and endocrine disruption.These changes lead to mechanical unloading in the bone microenvironment,insufficient blood perfusion,and calcium cycle disorders,which significantly impact the development of osteoporosis.(3)At present,the mechanism by which microgravity causes osteoporosis is relatively complex.A deeper study of these physiological mechanisms is crucial to ensuring the health of astronauts during long-term space missions,and provides a theoretical basis for the prevention and treatment of osteoporosis.
6.Resveratrol activates extracellular-regulated protein kinase 5 signaling protein to promote proliferation of mouse MC3T3-E1 cells
Yongkang NIU ; Zhiwei FENG ; Yaobin WANG ; Zhongcheng LIU ; Dejian XIANG ; Xiaoyuan LIANG ; Zhi YI ; Hongwei ZHAN ; Bin GENG ; Yayi XIA
Chinese Journal of Tissue Engineering Research 2025;29(5):908-916
BACKGROUND:The extracellular-regulated protein kinase 5(ERK5)signaling protein is essential for the survival of organisms,and resveratrol can promote osteoblast proliferation through various pathways.However,whether resveratrol can regulate osteoblast function through the ERK5 signaling protein needs further verification. OBJECTIVE:To explore the regulatory effect of ERK5 on the proliferation of MC3T3-E1 cells and related secreted proteins,and to further verify whether resveratrol can complete the above process by activating ERK5. METHODS:Mouse MC3T3-E1 preosteoblasts were treated with complete culture medium,XMD8-92(an ERK5 inhibitor),epidermal growth factor(an ERK5 activator),resveratrol alone,XMD8-92+EGF,and resveratrol+XMD8-92,respectively.Western blot assay was used to detect the expression of ERK5 and p-ERK5 proteins,proliferation-related proteins Cyclin D1,CDK4 and PCNA,and osteoblast-secreted proteins osteoprotegerin and receptor activator of nuclear factor-κB ligand in MC3T3-E1 cells of each group.The fluorescence intensity of ERK5,osteoprotegerin and receptor activator of nuclear factor-κB ligand in each group was detected by cell immunofluorescence staining,and cell proliferation was detected by EdU staining,respectively.The appropriate concentration and time of resveratrol intervention in MC3T3-E1 cells were determined by cell morphology observation and cell counting kit-8 assay. RESULTS AND CONCLUSION:The activation of ERK5 signaling protein could effectively promote the proliferation of MC3T3-E1 cells,up-regulate the osteoprotegerin/receptor activator of nuclear factor-κB ligand ratio.The appropriate concentration and time for resveratrol intervention in MC3T3-E1 cells was 5 μmol/L and 24 hours,respectively.Resveratrol could activate ERK5 signaling protein,thereby promoting osteoblast proliferation and up-regulating the osteoprotegerin/RANKL ratio.All these results indicate that resveratrol can promote the proliferation of MC3T3-E1 cells and up-regulate the osteoprotegerin/RANKL ratio by activating the ERK5 signaling protein.
7.Safety and efficacy of non-retrograde intubation combined with partially tubeless PCNL
Guangyuan YANG ; Xiaosong SUN ; Xiaoyuan QIAN ; Fuchao LIANG ; Linghui QIN
The Journal of Practical Medicine 2025;41(19):3072-3077
Objective To evaluate the safety and efficacy of non-retrograde intubation combined with selectively tubeless percutaneous nephrolithotomy(NR-ST-PCNL).Methods A retrospective analysis included 213 patients with upper urinary tract stones and hydronephrosis(renal pelvic separation>10 mm)undergoing PCNL at our hospital from October 2023 to June 2025.Patients were divided into Group A(non-retrograde intuba-tion,n=109)and Group B(retrograde intubation,n=104).Primary endpoint was postoperative complications and secondary endpoints included operative time,stone-free rate(SFR),visual analog scale(VAS)pain scores,postoperative hospital stay,and hospitalization costs.Results Group A demonstrated significantly lower rates of postoperative complications[7.3%(8/109)vs.18.2%(19/104),P=0.017],shorter operative time[51.00(37.00,65.00)min vs.71.50(55.00,90.75)min,P<0.001],lower postoperative VAS scores[1.00(0.00,1.00)vs.1.00(0.00,2.00),P=0.008],shorter hospital stay[3.00(2.00,3.00)days vs.4.00(4.00,4.00)days,P<0.001],and lower hospitalization costs[17 028.00(15 178.05,17 934.50)RMB vs.20 653.00(19 176.25,22 630.00)RMB,P<0.001]compared with Group B.There was no significant difference in SFR between groups(P>0.05).Conclusion For patients with upper urinary tract stones and renal pelvic separation>10 mm,NR-ST-PCNL performed by experienced surgeons achieves comparable stone clearance to conventional techniques while reducing complication risk,shortening operative and hospitalization times,and lowering costs.It represents a safe,efficient,and optimized clinical approach.
8.Safety and efficacy of non-retrograde intubation combined with partially tubeless PCNL
Guangyuan YANG ; Xiaosong SUN ; Xiaoyuan QIAN ; Fuchao LIANG ; Linghui QIN
The Journal of Practical Medicine 2025;41(19):3072-3077
Objective To evaluate the safety and efficacy of non-retrograde intubation combined with selectively tubeless percutaneous nephrolithotomy(NR-ST-PCNL).Methods A retrospective analysis included 213 patients with upper urinary tract stones and hydronephrosis(renal pelvic separation>10 mm)undergoing PCNL at our hospital from October 2023 to June 2025.Patients were divided into Group A(non-retrograde intuba-tion,n=109)and Group B(retrograde intubation,n=104).Primary endpoint was postoperative complications and secondary endpoints included operative time,stone-free rate(SFR),visual analog scale(VAS)pain scores,postoperative hospital stay,and hospitalization costs.Results Group A demonstrated significantly lower rates of postoperative complications[7.3%(8/109)vs.18.2%(19/104),P=0.017],shorter operative time[51.00(37.00,65.00)min vs.71.50(55.00,90.75)min,P<0.001],lower postoperative VAS scores[1.00(0.00,1.00)vs.1.00(0.00,2.00),P=0.008],shorter hospital stay[3.00(2.00,3.00)days vs.4.00(4.00,4.00)days,P<0.001],and lower hospitalization costs[17 028.00(15 178.05,17 934.50)RMB vs.20 653.00(19 176.25,22 630.00)RMB,P<0.001]compared with Group B.There was no significant difference in SFR between groups(P>0.05).Conclusion For patients with upper urinary tract stones and renal pelvic separation>10 mm,NR-ST-PCNL performed by experienced surgeons achieves comparable stone clearance to conventional techniques while reducing complication risk,shortening operative and hospitalization times,and lowering costs.It represents a safe,efficient,and optimized clinical approach.
9.A Comparison Study Between Flexible Ureteroscopy and Non-retrograde Percutaneous Nephrolithotomy in the Treatment of 1.5-2.0 cm Upper Ureteral Stones
Guangyuan YANG ; Xiaosong SUN ; Dongcao LIU ; Xiaoyuan QIAN ; Fuchao LIANG ; Linghui QIN
Chinese Journal of Minimally Invasive Surgery 2025;25(8):480-484
Objective To compare the efficacy and safety of flexible ureteral lithotripsy(FURL)and non-retrograde percutaneous nephrolithotomy(NR-PCNL)for treating1.5-2.0 cm upper ureteral stones.Methods We retrospectively analyzed clinical data of 130 patients with upper ureteral stones treated between October 2022 and October 2024.Sixty-two patients underwent FURL and 68 underwent NR-PCNL.Comparisons included operative time,pre-and postoperative changes in white blood cells(WBC),hemoglobin(Hb),and creatinine(Cr),postoperative C-reactive protein(CRP)levels,stone-free rate after primary surgery,postoperative hospitalization duration,pain scores,complications,and need for auxiliary treatments.Results Compared to the FURL group,the NR-PCNL group demonstrated advantages in operative time[54.0(44.3,69.3)min vs.82.5(66.0,101.0)min,Z=-5.565,P<0.001],WBC elevation[1.9(0.5,3.5)×109/L vs.4.5(3.0,6.0)×109/L,Z=-4.528,P<0.001],and secondary surgery rate[0%(0/68)vs.14.5%(9/62),P<0.001].The FURL group showed lower Hb reduction[3.0(2.0,6.3)g/L vs.8.0(5.0,11.0)g/L,Z=-4.262,P<0.001],less postoperative Visual Analogue Scale(VAS)pain scores[1.0(1.0,2.0)points vs.2.0(1.0,2.0)points,Z=-2.840,P=0.005],and shorter hospitalization duration[2.0(1.0,2.0)d vs.3.0(2.0,3.0)d,Z=-5.815,P<0.001].No significant differences were observed in Cr elevation,CRP levels,stone-free rate after primary surgery,complications,or analgesic requirements(P≥0.05).Conclusions Both NR-PCNL and FURL are safe and effective for 1.5-2.0 cm upper ureteral stones.FURL offers better patient comfort,while NR-PCNL shows superior overall safety.
10.Clinical application effects of tissue flaps prepared from the discarded limbs after amputation in patients with destructive wounds in the lower limbs
Mitao HUANG ; Zhiyou HE ; Pihong ZHANG ; Minghua ZHANG ; Xu CUI ; Le GUO ; Xiaoyuan HUANG ; Pengfei LIANG
Chinese Journal of Burns 2025;41(1):77-83
Objective:To explore the clinical application effects of tissue flaps prepared from the discarded limbs after amputation in patients with destructive wounds in the lower limbs.Methods:The study was a retrospective observational study. From March 2019 to March 2024, 7 male patients with destructive wounds in the lower limbs who met the inclusion criteria were admitted to the Department of Burns and Plastic Surgery of Xiangya Hospital of Central South University, aged 35 to 57 years. After clinical treatment, the damaged limbs were still difficult to preserve. Five patients with destructive wounds in the lower limbs were repaired with pedicled tissue flaps prepared from the discarded limbs after amputation, with wound areas of 15 cm×10 cm to 25 cm×15 cm and tissue flap incision areas of 15 cm×10 cm to 20 cm×15 cm. Two patients with destructive wounds in the lower limbs were repaired with free tissue flaps prepared from the discarded limbs after amputation, with wound areas of 22 cm×18 cm and 25 cm×15 cm and tissue flap incision areas of 23 cm×20 cm and 25 cm×18 cm. The survival of the tissue flap, the healing and appearance of wounds in the recipient site were followed up. At the last follow-up, the recovery status of the recipient site was evaluated according to the comprehensive flap evaluation scale, and the status of corrective prosthesis fitting was recorded.Results:During the follow-up of 6 to 24 months, all the tissue flaps successfully survived, with good healing and appearance of wounds in the recipient site. At the last follow-up, the scores of the recovery status of the recipient site ranged from 36 to 39 (with an average of 37.2). All amputated limbs were able to accommodate corrective prostheses with no distal ulceration.Conclusions:Utilizing tissue flaps prepared from the discarded limbs after amputation in patients with destructive wounds in the lower limbs to repair wounds effectively uses the discarded tissue and avoid creating new donor sites, which is a method to be considered for repairing multiple destructive wounds.

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