1.Human umbilical cord mesenchymal stem cell-derived exosomes attenuate renal ischemia-reperfusion injury by up-regulating ATF3 to inhibit the TLR4/NF-κB pathway
Xingyu* WAN ; Yujia LIU ; Ruiyan WANG ; Hao WANG ; Yi ZHAO ; Lu GUO ; Zhihua YANG ; Xinghua LÜ
Organ Transplantation 2026;17(2):275-286
Objective To investigate the protective effect and underlying mechanism of human umbilical cord mesenchymal stem cell-derived exosomes (hucMSC-Exo) on renal ischemia-reperfusion injury (IRI). Methods hucMSC-Exos were isolated and characterized. A mouse renal IRI model was established and the animals were divided into Sham, IRI, IRI+hucMSC-Exo, IRI+hucMSC-Exo+JY-2 and Sham+JY-2 groups. Serum creatinine (Scr) and blood urea nitrogen (BUN) were measured. Hematoxylin-eosin (HE) staining was used to evaluate renal histopathology. Enzyme-linked immune absorbent assay was performed to determine serum interleukin (IL)-1β and IL-18 levels. Western blotting was used to detect the expression of activating transcription factor 3 (ATF3), Toll-like receptor 4 (TLR4), nuclear factor (NF)-κB, NOD-like receptor protein 3 (NLRP3), cysteineyl aspartate specific proteinase (Caspase)-1 p20 and Gasdermin D(GSDMD). Real-time fluorescent quantitative polymerase chain reaction was employed to measure ATF3, TLR4 and NF-κB messenger RNA (mRNA). Immunohistochemistry was conducted to examine NLRP3, Caspase-1 p20 and GSDMD. An in vitro hypoxia/reoxygenation (H/R) model was established in HK-2 cells and divided into Control, H/R, H/R+hucMSC-Exo, H/R+hucMSC-Exo+JY-2 and Control+JY-2 groups. Western blotting was used to detect the expression of ATF3, TLR4 and NF-κB. Real-time fluorescent quantitative polymerase chain reaction was used to measure NLRP3, GSDMD and Caspase-1 mRNA. Results HucMSC-Exos were successfully isolated and identified. Compared with the Sham group, the IRI group exhibited elevated Scr and BUN, higher tubular injury scores, increased protein expression levels of ATF3, TLR4, NF-κB p65, NLRP3, Caspase-1 p20 and GSDMD, and raised mRNA expression levels of ATF3, TLR4, NF-κB. Compared with the IRI group, the IRI+hucMSC-Exo group showed decreased Scr and BUN, lower tubular injury scores, up-regulated ATF3 protein and mRNA, down-regulated TLR4, NF-κB p65, NLRP3, Caspase-1 p20 and GSDMD protein, and declined TLR4 and NF-κB mRNA. Compared with the IRI+hucMSC-Exo group, the IRI+hucMSC-Exo+JY-2 group exhibited increased Scr and BUN levels, elevated renal tubular injury scores, decreased ATF3 protein expression levels, elevated protein expression levels of TLR4, NF-κB p65, NLRP3, Caspase-1 p20, and GSDMD, decreased ATF3 mRNA expression levels, and elevated mRNA expression levels of TLR4 and NF-κB. (all P < 0.05). Compared with the Control group, the expression levels of ATF3, TLR4 and NF-κB p65 proteins were increased in the H/R group, and the expression levels of NLRP3, Caspase-1 and GSDMD mRNA were increased. Compared with the H/R group, the expression level of ATF3 protein was increased, the expression levels of TLR4 and NF-κB p65 proteins were decreased, and the expression levels of NLRP3, Caspase-1 and GSDMD mRNA were decreased in the H/R+hucMSC-Exo group. Compared with the H/R+hucMSC-Exo group, the expression level of ATF3 protein was decreased, the expression levels of TLR4 and NF-κB p65 proteins were increased, and the expression levels of NLRP3, Caspase-1 and GSDMD mRNA were increased in the H/R+hucMSC-Exo+JY-2 group (all P < 0.05). Conclusions HucMSC-Exos alleviate renal IRI by up-regulating ATF3, thereby negatively regulating the TLR4/NF-κB signaling pathway and subsequently inhibiting pyroptosis.
2.Evaluation of the feasibility and safety of a Chinese developed modular surgical robotic system for robot-assisted pyeloplasty
Shihao LIU ; Liqing XU ; Xinfei LI ; Kunlin YANG ; Zhaoying LI ; Zibo ZHANG ; Xiang WANG ; Wei-xiao FU ; Zhihua LI ; Xuesong LI
Journal of Peking University(Health Sciences) 2025;57(4):779-783
Objective:To evaluate the technical feasibility and perioperative safety of pyeloplasty assis-ted by the CarinaTM modular laparoscopic surgical robotic system in patients with ureteropelvic junction obstruction(UPJO).Methods:From November to December 2024,five consecutive patients diagnosed with UPJO underwent robot-assisted pyeloplasty using the CarinaTM modular laparoscopic surgical system at Peking University First Hospital.Data on patient demographics,intraoperative parameters(including docking time,console time,and estimated blood loss),perioperative outcomes,follow-up results,and surgeons' subjective evaluations of system performance were prospectively collected.Descriptive statistics were used;continuous variables were presented as median(range),and categorical variables as frequen-cy and percentage.Results:The cohort included four females and one male.All the patients successfully completed the robotic procedure without conversion to open or conventional laparoscopic surgery.The me-dian age was 32 years(24-37 years),and the median body mass index was 21.6 kg/m2(15.8-27.3 kg/m2).The median docking time was 8 min(3-12 min),and the median console time was 91 min(71-125 min).Intraoperative blood loss was uniformly 20 mL.The median postoperative drainage du-ration was 3 d(0-4 d),and the median length of hospital stay was 4 d(4-9 d).No Clavien-Dindo grade Ⅲ or higher complications occurred.All the patients had their double-J stents removed at 2 months postoperatively,and pain in the ipsilateral flank,reported preoperatively by all the five patients,was al-leviated.The subjective surgical success rate was 100%.Surgeons reported stable system performance throughout all the procedures,with no instances of mechanical arm interference or visual drift affecting surgical fluency.Conclusion:Preliminary findings indicate that pyeloplasty using the domestically deve-loped CarinaTM modular laparoscopic robotic system is technically feasible and perioperatively safe for the treatment of UPJO.
3.Surgical techniques and clinical outcomes of upper urinary tract reconstruction for stone-related ureteral strictures
Xiaoteng YU ; Yixuan HUANG ; Xinfei LI ; Changfu CHEN ; Fangzhou ZHAO ; Honggang YING ; Zihao TAO ; Yiming ZHANG ; Liqing XU ; Zhihua LI ; Kunlin YANG ; Liqun ZHOU ; Xuesong LI ; Zheng ZHAO
Journal of Peking University(Health Sciences) 2025;57(4):670-675
Objective:To summarize the surgical strategies and to evaluate the clinical outcomes of up-per urinary tract reconstruction in patients with stone-related ureteral strictures.Methods:This retro-spective study included 71 patients diagnosed with ureteral strictures secondary to urinary stones who un-derwent upper urinary tract reconstructive surgery at Peking University First Hospital between March 2014 and November 2023.Patient data were collected,including demographic characteristics,clinical presen-tation,laboratory results,imaging findings,surgical procedures,and follow-up outcomes.Ureteral stric-tures were classified according to anatomical location into upper,middle,lower,or multiple segments.Surgical procedures were carried out depending on the stricture characteristics.Surgical success was de-fined as resolution or improvement of clinical symptoms,radiographic improvement or stabilization of hy-dronephrosis,and maintenance of normal and stable renal function.Results:Among the 71 patients,36(50.7%)had strictures in the upper ureter,9(12.7%)in the middle ureter,15(21.1%)in the lower ureter,and 11(15.5%)had multifocal ureteral strictures.The median stricture length was 5.0 cm(interquartile range:3.0-15.0 cm).Surgical approach selection was individualized based on the location and extent of the stricture.For upper ureteral strictures,the most frequently employed techniques were oral mucosal graft ureteroplasty(13/36,36.1%)and appendiceal flap ureteroplasty(8/36,22.2%).Other options included ureteroureterostomy and ileal ureter replacement for longer or more complex strictures.In middle ureteral strictures,treatment was stratified by length:balloon dilation(1/9,11.1%)and ureteroureterostomy(1/9,11.1%)were applied in shorter strictures,while oral mucosal graft ureteroplasty(3/9,33.3%)and ileal ureter replacement(4/9,44.4%)were reserved for longer segments.For lower ureteral strictures,ureteral reimplantation into the bladder was the most common approach(10/15,66.7%),often combined with a psoas hitch or Boari flap when necessary.All the patients with multiple segmental strictures underwent ileal ureter replacement due to the extensive nature of the disease.The median follow-up period was 14.2 months(range:6.1-107.1 months).During follow-up,69 of 71 patients(97.2%)achieved surgical success.Conclusion:Stone-related ure-teral strictures present with considerable heterogeneity in terms of anatomical location,length,and com-plexity.Careful preoperative evaluation and individualized surgical planning are critical to successful re-construction.With appropriate selection of surgical methods,favorable long-term clinical outcomes can be achieved in the majority of patients.
4.Study on vestibular Schwannoma-derived exosomes inducing ferroptosis in HEI-OC1 cells
Maimaitiming DILIHUMAER ; Yuewen GAO ; Zhaohui WANG ; Zirong HUO ; Tao YANG ; Zhihua ZHANG
Journal of Audiology and Speech Pathology 2025;33(6):569-574
Objective To investigate the damage mechanism of extracellular vesicles(EVs)derived from ves-tibular schwannoma(VS)on HEI-OC1 cells and the protective effect of the ferroptosis inhibitor ferrostatin-1(Fer-1).Methods Tumor tissues and clinical data were collected from four patients with stage Ⅱ or Ⅲ VS,classified as grade D according to the AAO-HNS hearing classification.Primary VS cells were extracted,and their conditioned supernatant was collected.EVs were isolated using ultracentrifugation and identified.HEI-OC1 cells were cultured in vitro and divided into three groups:the control group(no treatment),the EVs group(treated with 3000 parti-cles/cell VS-EVs for 24 hours),and the EVs+Fer-1 group(pretreated with 20 μmol/L Fer-1 for 2 hours followed by co-culture with 3000 particles/cell VS-EVs for 24 hours).Cell viability was assessed using the CCK-8 assay,re-active oxygen species(ROS)levels were quantified using the DCFH-DA fluorescent probe,and lipid peroxidation was evaluated using the BODIPY 581/591 C11 probe.Results Compared with the control group,the EVs group showed significantly reduced cell viability(P<0.001)and increased levels of ROS(P<0.001)and lipid peroxides(P<0.001).However,the EVs+Fer-1 group exhibited significantly restored cell viability(P<0.001)and re-duced levels of ROS and lipid peroxidation(P<0.001).Conclusion VS-derived EVs disrupts redox homeostasis,promotes intracellular accumulation of lipid peroxides and ROS,and induces ferroptosis in HEI-OC1 cells.Fer-1 significantly alleviates VS-EVs-induced ferroptosis,thereby protecting HEI-OC1 cells from damage.
5.Cervical Kyphosis Based on Cervical Rehabilitation Training System:A Biomechanical Model Study
Zhihua LIU ; Mingwen ZHANG ; Yang ZHOU ; Yankui SHEN ; Zhongzhong CHEN
Journal of Medical Biomechanics 2025;40(3):615-622
Objective A biomechanical model of cervical kyphosis under the effects of axial traction load and lateral push load was establised,so as to provide a theoretical basis for the treatment of cervical curvature abnormalities,and formulate the most appropriate treatment plan for patients.Methods Based on the CT scan data of patients,the axial data of the cervical spine was extracted to fit the cervical curvature curve.Using the Timoshenko beam theory and the cervical rehabilitation training system,a mathematical model of cervical kyphosis was established for analytical calculations to obtain the recovery curve of the cervical spine under load and the total load required to cure cervical kyphosis,and its rationality was also verified.Results The biomechanical model of cervical kyphosis was established.Under the effects of axial traction load and lateral push load,the cervical spine effectively developed in the direction of physiological bending.The total axial load and lateral load were 353 N and 5 649 N,respectively,and the total axial load increased with the increase in traction angle.The therapeutic moment of the total lateral load decreased as the Bordon value increased.The therapeutic moment of the axial load was smaller than that of the lateral load in the range of normal Bordon value,confirming the rationality of the loads.Conclusions The established biomechanical model of cervical kyphosis can accurately simulate the biomechanical characteristics of the cervical spine,and the analysis results were valid,providing a mechanical theoretical basis for the design of treatment plans for patients.
6.Seven-step procedure for robot-assisted endoscopic thyroidectomy(BABA approach)
Zheng DING ; Bomin GUO ; Youben FAN ; Xianzhao DENG ; Ling ZHAN ; Xuanbin TAO ; Xiaohui GU ; Zixia TAO ; Zhihua XIA ; Jingfu SUN ; Bo YANG
Chinese Journal of General Surgery 2025;34(5):859-866
Traditional open thyroid surgery often leaves a scar on the neck,which can affect cosmetic outcomes.Therefore,various endoscopic thyroidectomy approaches via extra-cervical approaches have been developed.However,due to the unique anatomical characteristics of the neck and limitations of endoscopic instruments,conventional endoscopic techniques have certain drawbacks.Robot-assisted endoscopic thyroid surgery can help overcome these limitations.At present,robotic surgical systems remain expensive and the associated surgical costs are high,limiting their widespread adoption.Most surgeons are still relatively unfamiliar with the technique.Nevertheless,with ongoing technological advancements and cost reductions,robot-assisted surgery holds great promise for broader application.Based on years of large-scale experience in endoscopic thyroid surgery at our center,and drawing upon both domestic and international experiences with robotic thyroidectomy,this paper summarizes and proposes a seven-step protocol for robot-assisted endoscopic thyroidectomy via the bilateral axillo-breast approach,aiming to provide a practical reference for the clinical adoption of this technique.
7.The dominant deafness point mutation GJB2 p.D179N affects the oligomeric equilibrium of connexin 26
Huahong LUO ; Guohui HUANG ; Yunge GAO ; Tao YANG ; Hao WU ; Zhihua ZHANG
Journal of Audiology and Speech Pathology 2025;33(3):259-264
Objective To investigate the impact of the dominant deafness point mutation p.D179N on the oli-gomeric equilibrium state of Connexin 26(Cx26).Methods The wild-type Cx26 fusion protein(Cx26-WT-GFP)and mutant fusion proteins(Cx26-D179N-GFP,Cx26-D179C-GFP)were expressed in HEK293F cells.By using Fluorescence-detection size-exclusion chromatography(FSEC)and size-exclusion chromatography(SEC)to analysis the oligomeric state of the target protein based on malecular weight under the condition of solubilization and purifica-tion respectively.Cryo-electron microscopy(Cryo-EM)single particle analysis(SPA)was conducted to analysis the target protein's oligomeric states based on the 2D classification morphology of the protein particles.Results In vitro,the wild-type Cx26 protein(Cx26-WT)is almost exclusively dodecameric.The deafness mutation p.D179N protein(Cx26-D179N)exists as both dodecamers and hexamers,whereas the artificial mutation p.D179C protein(Cx26-D179C)does not form dodecamers.Conclusion The dominant deafness mutation GJB2 p.D179N could weaken the ability of docking between hexameric proteins,which could affect the balance between hexamers and do-decamers.
8.Introduction of the main addition and revision of the Chinese Pharmacopoeia 2025 Edition(Volume Ⅱ)
ZHOU Yi ; WANG Zhijun ; YUE Zhihua ; CHENG Qilei ; YUE Ruiqi ; YANG Xi ; GUO Wei ; MA Shuangcheng
Drug Standards of China 2025;26(1):023-027
The Pharmacopeia of the People’s Republic of China 2025 Edition (referred to as the Chinese Pharmacopoeia 2025 Edition, ChP 2025) will be promulgated and implemented. This article introduces the process of development of ChP 2025 Edition (Volume Ⅱ), including the selection, the revision of general notices,the addition and revision of drug monographs, etc., and provides some analysis and examples to illustrate,which can facilitate the readers to understand and implement the ChP 2025 Edition (Volume Ⅱ).
9.Consensus on informed consent for orthodontic treatment
Yang CAO ; Bing FANG ; Zuolin JIN ; Hong HE ; Yuxing BAI ; Lin WANG ; Haiping LU ; Zhihe ZHAO ; Tianmin XU ; Weiran LI ; Min HU ; Jinlin SONG ; Jun WANG ; Fang JIN ; Ding BAI ; Xianglong HAN ; Yuehua LIU ; Bin YAN ; Jie GUO ; Jiejun SHI ; Yongming LI ; Zhihua LI ; Xiuping WU ; Jiangtian HU ; Linyu XU ; Lin LIU ; Yi LIU ; Yanqin LU ; Wensheng MA ; Shuixue MO ; Liling REN ; Shuxia CUI ; Yongjie FAN ; Jianguang XU ; Lulu XU ; Zhijun ZHENG ; Peijun WANG ; Rui ZOU ; Chufeng LIU ; Lunguo XIA ; Li HU ; Weicai WANG ; Liping WU ; Xiaoxing KOU ; Jiali TAN ; Yuanbo LIU ; Bowen MENG ; Yuantao HAO ; Lili CHEN
Chinese Journal of Stomatology 2025;60(12):1327-1336
This consensus was developed by the Orthodontic Society of the Chinese Stomatological Association to provide a systematic, scientific, and practical guideline for informed consent in orthodontic care. Orthodontic treatment is typically lengthy, highly individualized, and involves multiple factors such as growth and development, occlusal function, and facial esthetics. Rapid technological advances and diverse risk profiles make the traditional reliance on orthodontist experience or institutional templates insufficient to ensure patients′ full understanding and autonomous decision-making. To address this, the expert panel conducted extensive reviews of domestic and international guidelines, analyzed representative dispute cases, and performed multicenter patient-clinician surveys. Using a multi-round Delphi method, the group established a standardized informed consent framework covering the initial consultation, treatment, and retention phases. The consensus emphasizes that informed consent is not only a fundamental legal and ethical requirement but also a key step in building trust, improving patient compliance, and enhancing treatment satisfaction. Orthodontists should clearly and comprehensively explain treatment plans, potential risks, uncertainties, and associated costs, while respecting the autonomy of patients or guardians, and maintain continuous communication and dynamic evaluation throughout the treatment process. The release of this consensus provides unified and authoritative guidance for clinical orthodontics, helping to standardize informed consent, enhance its transparency, safeguard patient rights, reduce medical risks, and promote high-quality, sustainable development of orthodontic practice.
10.Cervical Kyphosis Based on Cervical Rehabilitation Training System:A Biomechanical Model Study
Zhihua LIU ; Mingwen ZHANG ; Yang ZHOU ; Yankui SHEN ; Zhongzhong CHEN
Journal of Medical Biomechanics 2025;40(3):615-622
Objective A biomechanical model of cervical kyphosis under the effects of axial traction load and lateral push load was establised,so as to provide a theoretical basis for the treatment of cervical curvature abnormalities,and formulate the most appropriate treatment plan for patients.Methods Based on the CT scan data of patients,the axial data of the cervical spine was extracted to fit the cervical curvature curve.Using the Timoshenko beam theory and the cervical rehabilitation training system,a mathematical model of cervical kyphosis was established for analytical calculations to obtain the recovery curve of the cervical spine under load and the total load required to cure cervical kyphosis,and its rationality was also verified.Results The biomechanical model of cervical kyphosis was established.Under the effects of axial traction load and lateral push load,the cervical spine effectively developed in the direction of physiological bending.The total axial load and lateral load were 353 N and 5 649 N,respectively,and the total axial load increased with the increase in traction angle.The therapeutic moment of the total lateral load decreased as the Bordon value increased.The therapeutic moment of the axial load was smaller than that of the lateral load in the range of normal Bordon value,confirming the rationality of the loads.Conclusions The established biomechanical model of cervical kyphosis can accurately simulate the biomechanical characteristics of the cervical spine,and the analysis results were valid,providing a mechanical theoretical basis for the design of treatment plans for patients.

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