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Chondroitinase ABC combined with Schwann cell transplantation enhances restoration of neural connection and functional recovery following acute and chronic spinal cord injury

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Neural Regeneration Research 2025年第5期20卷 1467-1482页

作者： Wenrui Qu Xiangbing Wu Wei Wu Ying Wang Yan Sun Lingxiao Deng Melissa Walker Chen Chen Heqiao Dai Qi Han Ying Ding Yongzhi Xia George Smith Rui Li Nai-Kui Liu Xiao-Ming Xu Spinal Cord and Brain Injury Research Group Stark Neurosciences Research InstituteDepartment of Neurological SurgeryIndiana University School of MedicineIndianapolisINUSA department of Hand surgery the Second Hospital of Jilin UniversityChangchunJilin ProvinceChina Shriners Hospitals pediatric Research Center Temple University School of MedicinePhiladelphiaPAUSA department of Anatomy&Cell Biology Indiana University School of MedicineIndianapolisINUSA

Schwann cell transplantation is considered one of the most promising cell-based therapy to repair injured spinal cord due to its unique growth-promoting and myelin-forming properties.A the Food and Drug Administration-approved Phase I clinical trial has been conducted to evaluate the safety of transplanted human autologous Schwann cells to treat patients with spinal cord injury.A major challenge for Schwann cell transplantation is that grafted Schwann cells are confined within the lesion cavity,and they do not migrate into the host environment due to the inhibitory barrier formed by injury-induced glial scar,thus limiting axonal reentry into the host spinal *** we introduce a combinatorial strategy by suppressing the inhibitory extracellular environment with injection of lentivirus-mediated transfection of chondroitinase ABC gene at the rostral and caudal borders of the lesion site and simultaneously leveraging the repair capacity of transplanted Schwann cells in adult rats following a mid-thoracic contusive spinal cord *** report that when the glial scar was degraded by chondroitinase ABC at the rostral and caudal lesion borders,Schwann cells migrated for considerable distances in both rostral and caudal *** Schwann cell migration led to enhanced axonal regrowth,including the serotonergic and dopaminergic axons originating from supraspinal regions,and promoted recovery of locomotor and urinary bladder ***,the Schwann cell survival and axonal regrowth persisted up to 6 months after the injury,even when treatment was delayed for 3 months to mimic chronic spinal cord *** findings collectively show promising evidence for a combinatorial strategy with chondroitinase ABC and Schwann cells in promoting remodeling and recovery of function following spinal cord injury.

关键词： axonal regrowth bladder function chondroitinase ABC functional recovery glial scar lentivirus migration Schwann cell spinal cord injury transplantation

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Integration of perioperative features and intragraft TCF7L2 expression to predict lipid metabolic disorder in liver transplant recipients

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Science China Life Sciences 2025年第1期68卷 297-299页

作者： Junbin Zhou Rongli Wei Guanghan Fan Zhengxing Lian Xuanyu Zhang Linsong Tang Zhetuo Qi Haiyang Xie Shusen Zheng Qiang Wei Xiao Xu department of Hepatobiliary and Pancreatic surgery People's Hospital of LishuiAffiliated Lishui Hospital of Wenzhou Medical UniversityThe First Affiliated Hospital of Lishui University NHFPC Key Laboratory of Combined Multi-Organ Transplantation Key Laboratory of Integrated Oncology and Intelligent Medicine of Zhejiang Province Department of Hepatobiliary and Pancreatic SurgeryHangzhou First People's Hospital department of Hepatobiliary and Pancreatic surgery The First Affiliated HospitalZhejiang University School of Medicine department of urology The Second Affiliated HospitalZhejiang University School of Medicine department of Hepatobiliary and Pancreatic surgery Department of Liver TransplantationShulan (Hangzhou) Hospital Hangzhou Medical College Zhejiang University School of Medicine

Dear Editor, Liver transplantation(LT) is the only curative therapy for patients with endstage liver disease(He et al., 2023; Ling et al., 2022). Post-transplant hypertriglyceridemia(PTHT), which has an incidence of up to 32.8% in 6 months after LT, is one of the major post-transplant complications(Toshima et al., 2020).

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Inflammasome links traumatic brain injury, chronic traumatic encephalopathy, and Alzheimer's disease

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Neural Regeneration Research 2025年第6期20卷 1644-1664页

作者： Gabriela Seplovich Yazan Bouchi Juan Pablo de Rivero Vaccari Jennifer C.Munoz Pareja Andrew Reisner Laura Blackwell Yehia Mechref Kevin K.Wang J.Adrian Tyndall Binu Tharakan Firas Kobeissy department of surgery Morehouse School of MedicineAtlantaGAUSA department of Neurobiology Center for NeurotraumaMultiomics&Biomarkers(CNMB)Neuroscience InstituteMorehouse School of MedicineAtlantaGAUSA department of Neurological surgery and the Miami Project to Cure Paralysis University of Miami Miller School of MedicineMiamiFLUSA Division of pediatric Critical Care Department of PediatricsUniversity of Miami Miller School of MedicineMiamiFLUSA department of pediatrics Emory UniversityAtlantaGAUSA department of Neurosurgery Children’s Healthcare of AtlantaAtlantaGAUSA department of Chemistry and Biochemistry Texas Tech UniversityLubbockTXUSA Morehouse School of Medicine AtlantaGAUSA

Traumatic brain injury, chronic traumatic encephalopathy, and Alzheimer's disease are three distinct neurological disorders that share common pathophysiological mechanisms involving neuroinflammation. One sequela of neuroinflammation includes the pathologic hyperphosphorylation of tau protein, an endogenous microtubule-associated protein that protects the integrity of neuronal cytoskeletons. Tau hyperphosphorylation results in protein misfolding and subsequent accumulation of tau tangles forming neurotoxic aggregates. These misfolded proteins are characteristic of traumatic brain injury, chronic traumatic encephalopathy, and Alzheimer's disease and can lead to downstream neuroinflammatory processes, including assembly and activation of the inflammasome complex. Inflammasomes refer to a family of multimeric protein units that, upon activation, release a cascade of signaling molecules resulting in caspase-induced cell death and inflammation mediated by the release of interleukin-1β cytokine. One specific inflammasome, the NOD-like receptor protein 3, has been proposed to be a key regulator of tau phosphorylation where it has been shown that prolonged NOD-like receptor protein 3 activation acts as a causal factor in pathological tau accumulation and spreading. This review begins by describing the epidemiology and pathophysiology of traumatic brain injury, chronic traumatic encephalopathy, and Alzheimer's disease. Next, we highlight neuroinflammation as an overriding theme and discuss the role of the NOD-like receptor protein 3 inflammasome in the formation of tau deposits and how such tauopathic entities spread throughout the brain. We then propose a novel framework linking traumatic brain injury, chronic traumatic encephalopathy, and Alzheimer's disease as inflammasomedependent pathologies that exist along a temporal continuum. Finally, we discuss potential therapeutic targets that may intercept this pathway and ultimately minimize long-term neurological decline.

关键词： Alzheimer's disease caspase-1 chronic traumatic encephalopathy inflammasomes neurodegeneration neuroinflammation NLRP1 NLRP3 pyroptosis tauopathy traumatic brain injury

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Comparison of ART outcomes in men with altered mRNA protamine 1/protamine 2 ratio undergoing intracytoplasmic sperm injection with ejaculated and testicular spermatozoa

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Asian Journal of andrology 2020年第6期22卷 623-628页

作者： Jonas Sarasa Maria Enciso Laura Garcia Andrea Leza Klaus Steger Jon Aizpurua iGLS Alicante 03540SpainMolecular AndrologyJustus-Liebig-UDiversity GiessenGiessen 35385Germany IVF-Spain Alicante 03540SpainMolecular AndrologyJustus-Liebig-UDiversity GiessenGiessen 35385Germany department of urology Pediatric Urology and AndrologyMolecular AndrologyJustus-Liebig-UDiversity GiessenGiessen 35385Germany

Assisted reproductive technologies invoIving the use of spermatozoa and eggs for in vitro fertilization(IVF)have come as the solution for many infertile couples to become ***,in some cases,the use of ejaculated spermatozoa delivers poor IVF *** studies have suggested the use of testicular spermatozoa in severe male in fertility cases,but no guideli nes regarding their utilization are currently *** the present study,we found the mRNA protamine 1/protamine 2(P1/P2)ratio to be a valuable biomarker of poor sperm function that could be used as a diagnostic key for the identification of cases that would benefit from the use of testicular spermatozoa.A total of 23 couples undergoing egg donation cycles with at least one previous cycle failure were *** couples underwent two consecutive intracytoplasmic sperm injection(ICSI)cycles with either ejaculated or testicular spermatozoa(TESA).The sperm mRNA P1/P2 ratio,fertilization rate,blastocyst rate,and pregnancy and live birth rate were *** showed improved ICSI and clinical outcomes in cycles with testicular spermatozoa in men with altered mRNA P1/P2 *** cycles presented significantly higher rates of fertilization(mean±standard deviation:76.1%±15.1%vs 65.5%±18.8%),blastocyst formation(55.0%±20.3%vs 30.8%±23.8%),and good morphological quality blastocyst(28.9%±22.9%vs 13.5%±17.9%)and also improvements on pregnancy(60.9%vs 0%)and healthy birth rates(56.5%vs 0%)than EJACULATE *** results described here suggest that in patients with previous IVF/ICSI failures and aberrant mRNA protamine ratios,the use of testicular spermatozoa may be a good alternative to improve clinical outcomes.

关键词： DNA damage male infertility mRNA protamine ratio sperm chromatin testicular spermatozoa

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Comparison of perioperative outcomes between laparoscopic and open partial splenectomy in children and adolescents

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World Journal of Gastrointestinal surgery 2021年第9期13卷 979-987页

作者： Mohamed Makansi Martin Hutter Till-Martin Theilen Henning C Fiegel Udo Rolle Stefan Gfroerer department of pediatric surgery and pediatric urology University Hospital FrankfurtFrankfurt am Main 60590Germany department of pediatric surgery and pediatric urology Helios Clinic Berlin-BuchBerlin 13125Germany

BACKGROUND In order to avoid consequences of total splenectomy,partial splenectomy(PS)is increasingly *** purpose of this study was to compare perioperative outcomes of laparoscopic PS(LPS)and open PS(OPS)in children and *** To compare perioperative outcomes of patients with LPS and *** After institutional review board approval,a total of 26 patients that underwent LPS or OPS between January 2008 and July 2018 were identified from the database of our tertiary referral *** total,10 patients had LPS,and 16 patients underwent *** loss was calculated by Mercuriali’s *** scores,analgesic requirements and complications were *** Wilcoxon rank sum test was used for *** compare categorical variables,Fisher’s exact test was *** LPS was performed in 10 patients;16 patients had ***(except for body mass index and duration of follow-up),indicating primary disease,preoperative spleen size and postoperative spleen volume,perioperative hematological parameters,postoperative pain scores,analgesic requirements,adverse events according to the Clavien-Dindo classification and the comprehensive complication index,median time from operation to initiation of feeds,median time from operation to full feeds,median time from operation to mobilization and median length of hospital stay did not differ between LPS and ***(range)operative time(min)was longer in LPS compared to the OPS group[185(135-298)vs 144(112-270),respectively;P=0.048].Calculated perioperative blood loss(mL of red blood cell count)was higher in the LPS group compared to OPS[87(-45-777)vs-37(-114-553),respectively;P=0.039].CONCLUSION This is the first study that compared outcomes of LPS and *** operative approaches had comparable perioperative *** appears to be a viable alternative to OPS.

关键词： Laparoscopic vs open Laparoscopy Partial splenectomy Perioperative outcome Children Adolescents

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Benign penile skin anomalies in children:a primer for pediatricians

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World Journal of pediatrics 2015年第4期11卷 316-323页

作者： Marco Castagnetti Mike Leonard Luis Guerra Ciro Esposito Marcello Cimador Section of pediatric urology Urology UnitUniversity Hospital of PadovaPaduaItaly department of surgery Division of Pediatric UrologyChildren's Hospital of Eastern OntarioUniversity of OttawaOttawaONCanada department of pediatrics Federico II University of NaplesItaly Section of pediatric urology and pediatric surgery Unit Department for Mother&Child Care and UrologyUniversity of PalermoPalermoItaly

Background:Abnormalities involving the skin coverage of the penis are diffi cult to defi ne,but they can significantly alter penile appearance,and be a cause of parental *** sources:The present review was based on a non-systematic search of the English language medical literature using a combination of key words including"penile skin anomalies"and the specific names of the different ***:Conditions were addressed in the following order,those mainly affecting the prepuce(phimosis,balanitis xerotica obliterans,balanitis,paraphimosis),those which alter penile configuration(inconspicuous penis and penile torsion),and lastly focal lesions(cysts,nevi and vascular lesions).Most of these anomalies are congenital,have no or minimal influence on urinary function,and can be detected on clinical *** improvement is *** the majority of cases undergoing surgery,the potential psychological implications of genital malformation on patient development are the main reason for treatment,and the age generally recommended for surgery is after 12 months of ***:This review provides the pediatrician with a handy tool to identify the most common penile skin anomalies,counsel parents adequately,make sensible and evidence based choices for management,and recognize complications or untoward outcomes in patients undergoing surgery.

关键词： balanitis xerotica obliterans foreskin penis phimosis

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Association between 5α-reductase inhibitors therapy and incidence, cancer-specific mortality,and progression of prostate cancer: evidence from a meta-analysis

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Asian Journal of andrology 2020年第5期22卷 532-538页

作者： Lian-Min Luo Re-Dian Yang Jia-Min Wang Shan-Kun Zhao Yang-Zhou Liu Zhi-Guo Zhu Qian Xiang Zhi-Gang Zhao department of urology and andrology Minimally Invasive Surgery CenterGuangdong Provincial Key Laboratory of UrologyThe First Affiliated Hospital of Guangzhou Medical UniversityGuangzhou 510230China.

5a-reductase inhibitors(5-ARI)are widely employed for the treatment of benign prostatic *** has been noted that 5-ARI exhibit the potential to attenuate the risk of prostate cancer,but consistent agreement has not been ***,the effect of 5-ARI on cancer-specific mortality and progression of prostate cancer remains ***,the goal of the current meta-analysis was to elucidate the impact of 5-ARI on the incidence and progression of prostate *** searched for all studies assessing the effect of 5-ARI on risk of prostate cancer in PubMed,Embase,Medline,and Cochrane Library *** relative risk(RR)and corresponding 95%confidence intervals(CIs)were accepted to evaluate the association between 5-ARI and the risk of prostate *** results implied that subjects who accepted 5-ARI compared with the placebo group experienced a distinctly weakened overall incidence of prostate cancer(RR=0.74;95%C l:0.66-0.82;P7;RR=1.19;95%Cl:0.98-1.43;P=0.069).The results also showed that 5-ARI treatment did not significantly alter prostate cancer-specific mortality(RR=1.0;95%C l:0.95-1.05;P=0.916).In addition,it was worth noting that 5-ARI treatment acted in a protective role that presented a dramatic benefit to delay the progression of low-risk tumors(RR=0.58;95%C l:0.43-0.78;P<0.001).

关键词： 5a-reductase inhibitor meta-analysis prostate cancer

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Comparison of outcomes between complete and incomplete congenital duodenal obstruction

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World Journal of Gastroenterology 2019年第28期25卷 3787-3797页

作者： Stefan Gfroerer Till-Martin Theilen Henning C Fiegel Anoosh Esmaeili Udo Rolle department of pediatric surgery and pediatric urology University Hospital Frankfurt Frankfurt 60590 Germany department of pediatric Cardiology University Hospital Frankfurt Frankfurt 60590 Germany

BACKGROUND Congenital duodenal obstruction (CDO) can be complete (CCDO) or incomplete (ICDO). To date there is no outcome analysis available that compares both subtypes. AIM To quantify and compare the association between CCDO and ICDO with outcome parameters. METHODS We retrospectively reviewed all patients who underwent operative repair of CCDO or ICDO in our tertiary care institution between January 2004 and January 2017. The demographics, clinical presentation, preoperative diagnostics and postoperative outcomes of 50 patients were compared between CCDO (n = 27;atresia type 1-3, annular pancreas) and ICDO (n=23;annular pancreas, web, Ladd′s bands). RESULTS In total, 50 patients who underwent CDO repair were enrolled and followed for a median of 5.2 and 3.9 years (CCDO and ICDO, resp.). CCDO was associated with a significantly higher prenatal ultrasonographic detection rate (88% versus 4%;CCDO vs ICDO, P<0.01), lower gestational age at birth, lower age and weight at operation, higher rate of associated congenital heart disease (CHD), more extensive preoperative radiologic diagnostics, higher morbidity according to Clavien-Dindo classification and comprehensive complication index (all P≤0.01). The subgroup analysis of patients without CHD and prematurity showed a longer time from operation to the initiation of enteral feeds in the CCDO group (P<0.01). CONCLUSION CCDO and ICDO differ with regard to prenatal detection rate, gestational age, age and weight at operation, rate of associated CHD, preoperative diagnostics and morbidity. The degree of CDO in mature patients without CHD influences the postoperative initiation of enteral feeding.

关键词： Congenital duodenal obstruction Duodenal atresia Duodenal stenosis Prenatal ultrasonographic detection rate Clinical presentation Preoperative diagnostics Adverse events Outcome

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pediatric intestinal motility disorders

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World Journal of Gastroenterology 2015年第33期21卷 9683-9687页

作者： Stefan Gfroerer Udo Rolle department of pediatric surgery and pediatric urology Goethe-University Frankfurt/M.60590 Frankfurt/M.Germany

pediatric intestinal motility disorders affect many children and thus not only impose a significant impact on pediatric health care in general but also on the quality of life of the affected ***,some of these conditions might also have implications for *** intestinal motility disorders frequently present as chronic constipation in toddler age *** of these conditions are functional,meaning that constipation does not have an organic etiology,but in 5% of the cases,an underlying,clearly organic disorder can be *** with organic causes for intestinal motility disorders usually present in early infancy or even right after *** most striking clinical feature of children with severe intestinal motility disorders is the delayed passage of meconium in the newborn *** sign is highly indicative of the presence of Hirschsprung disease(HD),which is the most frequent congenital disorder of intestinal *** is a rare but important congenital disease and the most significant entity of pediatric intestinal motility *** etiology and pathogenesis of HD have been extensively studied over the last several decades.A defect in neural crest derived cell migration has been proven as an underlying cause of HD,leading to an aganglionic distal end of the *** basic science and clinical research related studies have been conducted to better diagnose and treat *** of the aganglionic bowel remains the gold standard for treatment of *** recent studies show,at least experimentally,the possibility of a stem cell based therapy for *** editorial also includes rare causes of pediatric intestinal motility disorders such as hypoganglionosis,dysganglionosis,chronic intestinal pseudo-obstruction and ganglioneuromatosis in multiple endocrine *** organic pathologies are rare in pediatric intestinal motility disorders but must be recognized as early as possible.

关键词： Intestinal motility disorder Children Hirschsprung

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Epididymitis： revelations at the convergence of clinical and basic sciences

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Asian Journal of andrology 2015年第5期17卷 756-763,I0007页

作者： Vera Michel Adrian Pilatz Mark P Hedger Andreas Meinhardt department of Anatomy and Cell Biology department of urology Pediatric Urology and Andrology Justus-Liebig-University of Giessen 35385 Giessen Germany Centre for Reproductive Health MIMR-PHI Institute of Medical Research Melbourne Victoria Australia

Acute epididymitis represents a common medical condition in the urological outpatient clinic. Mostly, epididymitis is caused by bacterial ascent through the urogenital tract, with pathogens originating either from sexually transmitted diseases or urinary tract infections. Although conservative antimicrobial therapy is possible in the majority of patients and is usually sufficient to eradicate the pathogen, studies have shown persistent oligozoospermia and azoospermia in up to 40% of these patients. Animal models of epididymitis are created to delineate the underlying reasons for this observation and the additional impairment of sperm function that is often associated with the disease. Accumulated data provide evidence of a differential expression of immune cells, immunoregulatory genes and pathogen-sensing molecules along the length of the epididymal duct. The evidence suggests that a tolerogenic environment exists in the caput epididymidis, but that inflammatory responses are most intense toward the cauda epididymidis. This is consistent with the need to provide protection for the neo-antigens of spermatozoa emerging from the testis, without compromising the ability to respond to ascending infections. However, severe inflammatory responses, particularly in the cauda, may lead to collateral damage to the structure and function of the epididymis. Convergence of the clinical observations with appropriate animal studies should lead to better understanding of the immunological environment throughout the epididymis, the parameters underlying susceptibility to epididymitis, and to therapeutic approaches that can mitigate epididymal damage and subsequent fertility problems.

关键词： acute epididymitis animal models of bacterial epididymitis epididymal duct epididymal immune environment fertility

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