Meconium is changed from defoliated intestinal villi with apoptosis. A meconium corpuscle is a limited architecture in the meconium at the light microscopic level. In histological and immunohistochemical sections of the abdomen from 40 fetuses at 20–31 weeks of gestation, we found 12 fetuses with meconium and examined the architecture.A solid or loose meconium was seen depending on sites. The solid meconium in the colon and rectum contained numerous spherical or rugby ball-like corpuscles comprising of a core with tightly-packed atrophied cells and a laminar fibrous sheath.The solid meconium surrounded and incorporated villi that maintained the original architecture. The loose meconium was seen not only in the stomach and duodenum but also, depending on specimens, in the colon and rectum. It was composed of a large mucosal fold, a single small villus and/or fragmented epithelia. Notably, these mucosal tissues still contained chromogranin-positive gastrointestinal cells and cytokeratin-positive epithelia. A large ring-like meconium was composed of the entirely circular mucosa or epithelia that seemed to be detached along the muscularis mucosae or the basal lamina.A sheath-like fibrous structure in meconium seemed to originate from the lamina propria and basal lamina of villi. A defoliation of villi with apoptosis seemed difficult to explain a detachment of the entirely circular mucosa or epithelia in large fetuses examined. The latter event might require a specific mechanism such as an in utero intussusception in which a proximal side of the colon was invaginated into the distal lumen.

OBJECTIVE: To explore the effect of acupuncture therapy on dysphagia in patients with Parkinson's disease. METHODS: This randomized controlled study lasted 42 days and included 112 patients with Parkinson's disease and dysphagia. Participants were randomly assigned to the experimental and control groups (56 cases each group) using the completely randomized design, all under routine treatment. The experimental group was given acupuncture therapy. The primary outcome was Penetration-Aspiration Scale (PAS). The secondary outcomes were (1) Standardized Swallowing Assessment (SSA), and (2) nutritional status including body mass index (BMI), serum albumin, prealbumin, and hemoglobin. Adverse events were recorded as safety indicators. RESULTS: One participant quitted the study midway. There were no significant differences in baseline assessment (P>0.05). After treatment, both groups showed significant improvement in PAS, SSA and nutritional status except for BMI of the control group. There were significant differences between the two groups in the PAS for both paste and liquid, SSA (25.18±8.25 vs. 20.84±6.92), BMI (19.97±3.34 kg/m²vs. 21.26 ±2.38 kg/m²), serum albumin (35.16 ±5.29 g/L vs. 37.24 ±3.98 g/L), prealbumin (248.33 ±27.72 mg/L vs. 261.39 ±22.10 mg/L), hemoglobin (119.09±12.53 g/L vs. 126.67±13.97 g/L) (P<0.05). There were no severe adverse events during the study. CONCLUSION: The combination of routine treatment and acupuncture therapy can better improve dysphagia and nutritional status in patients with Parkinson's disease, than routine treatment solely. (registration No. CLINICALTRIAL gov NCT06199323).
Humans ; Parkinson Disease/therapy* ; Deglutition Disorders/physiopathology* ; Acupuncture Therapy/adverse effects* ; Male ; Female ; Aged ; Middle Aged ; Treatment Outcome ; Nutritional Status ; Body Mass Index

T-cell acute lymphoblastic leukemia (T-ALL) is a highly aggressive hematologic malignancy with a poor prognosis, despite advancements in treatment. Many patients struggle with relapse or refractory disease. Investigating the role of the super-enhancer (SE) regulated gene ubiquitin-specific protease 20 (USP20) in T-ALL could enhance targeted therapies and improve clinical outcomes. Analysis of histone H3 lysine 27 acetylation (H3K27ac) chromatin immunoprecipitation sequencing (ChIP-seq) data from six T-ALL cell lines and seven pediatric samples identified USP20 as an SE-regulated driver gene. Utilizing the Cancer Cell Line Encyclopedia (CCLE) and BloodSpot databases, it was found that USP20 is specifically highly expressed in T-ALL. Knocking down USP20 with short hairpin RNA (shRNA) increased apoptosis and inhibited proliferation in T-ALL cells. In vivo studies showed that USP20 knockdown reduced tumor growth and improved survival. The USP20 inhibitor GSK2643943A demonstrated similar anti-tumor effects. Mass spectrometry, RNA-Seq, and immunoprecipitation revealed that USP20 interacted with hypoxia-inducible factor 1 subunit alpha (HIF1A) and stabilized it by deubiquitination. Cleavage under targets and tagmentation (CUT&Tag) results indicated that USP20 co-localized with HIF1A, jointly modulating target genes in T-ALL. This study identifies USP20 as a therapeutic target in T-ALL and suggests GSK2643943A as a potential treatment strategy.

This study aimed to introduce a modified Byars staged procedure and investigate its application value in patients with severe hypospadias. We retrospectively analyzed the clinical data of patients with severe hypospadias admitted to the First Affiliated Hospital of Sun Yat-sen University (Guangzhou, China) between October 2012 and October 2022. In total, 31 patients underwent the conventional Byars procedure (conventional group), and 45 patients underwent the modified Byars staged procedure (modified group). Our modified strategy was built upon the standard Byars procedure by incorporating glansplasty during the first stage and employing a Y-shaped flap in conjunction with a glandular tunnel for urethroplasty during the second stage. Notably, there were no statistically significant differences in the preoperative baseline characteristics, duration of surgery, amount of blood loss, or occurrence of postoperative complications, including urethral fistula, stricture and diverticulum, or penile curvature, between the conventional and modified groups. However, there was a significantly lower incidence of coronal sulcus fistula (0 vs 16.1%, P = 0.02) and glans dehiscence (0 vs 12.9%, P = 0.02) in the surgical group than that in the conventional group. In addition, the modified group exhibited a notably greater rate of normotopic urethral opening (100.0% vs 83.9%, P = 0.01) and a higher mean score on the Hypospadias Objective Penile Evaluation (HOPE; mean ± standard error of mean: 8.6 ± 0.2 vs 7.9 ± 0.3, P = 0.02) than did the conventional group. In conclusion, the modified Byars staged procedure significantly reduced the risks of glans dehiscence and coronal sulcus fistula. Consequently, it offers a promising approach for achieving favorable penile esthetics, thereby providing a reliable therapeutic option for severe hypospadias.
Humans ; Hypospadias/surgery* ; Male ; Retrospective Studies ; Urologic Surgical Procedures, Male/methods* ; Child, Preschool ; Child ; Postoperative Complications/etiology* ; Urethra/surgery* ; Plastic Surgery Procedures/methods* ; Surgical Flaps ; Penis/surgery* ; Treatment Outcome ; Infant

The aim of this investigation was to determine the optimal storage medium for testicular hypothermic transportation and identify the ideal concentration for the application of the protective agent 5-aminolevulinic acid (5-ALA). Furthermore, this study aimed to explore the underlying mechanism of the protective effects of 5-ALA. First, we collected and stored mouse testicular fragments in different media, including Hank's balanced salt solution (HBSS; n = 5), Dulbecco's Modified Eagle Medium/Nutrient Mixture F-12 (DMEM/F12; n = 5), and alpha-minimum essential medium (αMEM; n = 5). Storage of testicular tissue in HBSS preserved the integrity of testicular morphology better than that in the DMEM/F12 group ( P < 0.05) and the αMEM group ( P < 0.01). Testicular fragments were subsequently placed in HBSS with various concentrations of 5-ALA (0 [control], 1 mmol l -1 , 2 mmol l -1 , and 5 mmol l -1 ) to determine the most effective concentration of 5-ALA. The 2 mmol l -1 5-ALA group ( n = 3) presented the highest positive rate of spermatogonial stem cells compared with those in the control, 1 mmol l -1 , and 5 mmol l -1 5-ALA groups. Finally, the tissue fragments were preserved in HBSS with control ( n = 3) and 2 mmol l -1 5-ALA ( n = 3) under low-temperature conditions. A comparative analysis was performed against fresh testes ( n = 3) to elucidate the underlying mechanism of 5-ALA. Gene set enrichment analysis (GSEA) for WikiPathways revealed that the p38 mitogen-activated protein kinase (MAPK) signaling pathway was downregulated in the 2 mmol l -1 5-ALA group compared with that in the control group (normalized enrichment score [NES] = -1.57, false discovery rate [FDR] = 0.229, and P = 0.019). In conclusion, these data suggest that using 2 mmol l -1 5-ALA in HBSS effectively protected the viability of spermatogonial stem cells upon hypothermic transportation.
Male ; Animals ; Testis/cytology* ; Aminolevulinic Acid/pharmacology* ; Mice ; Organ Preservation/methods* ; Organ Preservation Solutions/pharmacology* ; Cryopreservation/methods*

Poor water solubility is the primary obstacle preventing the development of many pharmacologically active compounds into oral preparations. Self-nanoemulsifying drug delivery systems(SNEDDS) have become a widely used strategy to enhance the oral bioavailability of poorly soluble drugs by inducing a supersaturated state, thereby improving their apparent solubility and dissolution rate. However, the supersaturated solutions formed in SNEDDS are thermodynamically unstable systems with solubility levels exceeding the crystalline equilibrium solubility, making them prone to drug precipitation in the gastrointestinal tract and ultimately hindering drug absorption. Therefore, maintaining a stable supersaturated state is crucial for the effective delivery of poorly soluble drugs. Incorporating polymers as precipitation inhibitors(PPIs) into the formulation of supersaturated self-nanoemulsifying drug delivery systems(S-SNEDDS) can inhibit drug aggregation and crystallization, thus maintaining a stable supersaturated state. This has emerged as a novel preparation strategy and a key focus in SNEDDS research. This review explores the preparation design of SNEDDS and the technical challenges involved, with a particular focus on polymer-based S-SNEDDS for enhancing the solubility and oral bioavailability of poorly soluble drugs. It further elucidates the mechanisms by which polymers participate in transmembrane transport, summarizes the principles by which polymers sustain a supersaturated state, and discusses strategies for enhancing drug absorption. Altogether, this review provides a structured framework for the development of S-SNEDDS preparations with stable quality and reduced development risk, and offers a theoretical reference for the application of S-SNEDDS technology in improving the oral bioavailability of poorly soluble drugs.
Solubility ; Administration, Oral ; Polymers/chemistry* ; Drug Delivery Systems/methods* ; Humans ; Emulsions/chemistry* ; Biological Availability ; Animals ; Pharmaceutical Preparations/administration & dosage*

Objective:To evaluate the efficacy and feasibility of a domestically developed robotic surgical system based on fiber-optic dedicated line communication in cross-regional urological telesurgery.Methods:This was multicenter，single-arm，retrospective case series study. The data of patients who underwent urological telesurgeries using the telesurgical system between January 2023 and December 2024 were analyzed. The cohort included 59 patients from seven hospitals across China. Among the patients，47 were male（79.7%）and 12 were female（20.3%），with a median age of 63.0（56.0，68.0）years and a body mass index of（24.7 ± 3.0）kg/m 2. Surgical procedures included 32 radical prostatectomies，24 partial nephrectomies，one radical nephrectomy，one adrenalectomy，and one ureteral reconstruction. The perioperative indicators，pathological results and postoperative complications were analyzed. The network monitoring data were collected，and the perioperative data of patients，remote system monitoring data and costs were compared between the two communication modes of optical transport network（OTN）and cloud-connect network（CCN）. Results:All 59 remote surgeries were successfully completed，with a mean operative time of（138.0 ± 54.0）minutes，median intraoperative blood loss of 50.0（30.0，100.0）ml and a postoperative hospital stay of 5.0（4.0，6.0）days. No cases required reoperation，Clavien-Dindo grade ≥3 complications，or readmission. The geographical distance between the primary and remote surgical sites ranged from 450 to 2 800 km. Network monitoring revealed increased bidirectional latency with distance increasing：the shortest latency time（Hefei-Hangzhou，450 km）was（16.59 ± 0.80）ms，while the longest（Harbin-Hangzhou，2 200 km）latency time was（53.31 ± 0.31）ms. Average frame loss per procedure was 0?1.27 frames. The results of subgroup analysis comparing OTN and CCN communication modes showed no significant differences in operative time［（130.7 ± 70.5）minutes vs.（142.1 ± 42.9）minutes， P = 0.442］，postoperative hospitalization［6.0（4.0，8.0）d vs. 5.0（4.0，6.0）d， P = 0.581］，or readmission rates（0 vs. 0）. However，CCN demonstrated significant cost advantages with 500 RMB per operation vs. 3 000 RMB per operation for OTN. Conclusions:Urological telesurgery using fiber-optic communication is feasible. The CCN mode，with its cost-effectiveness，excellent usability，and multi-point interconnection flexibility，is currently the preferred communication model for telesurgical applications.

Objective To understand the clinical applicability and implementation of expert consensus on the implementation and removal of protective restraints in psychiatry,and to provide references for promoting the standardized practice of psychiatric protective restraints and updating the consensus.Methods By the convenience sampling method,a questionnaire survey was conducted among nurses from 480 hospitals in 30 provinces from June 15 to July 15,2024.The survey was conducted using the instrument for evaluating clinical applicability of guide-lines(version 2.0)and a self-compiled questionnaire on the clinical implementation of the restraint consensus.Results A total of 7,844 valid questionnaires were collected,with a valid questionnaire recovery rate of 93.78％.The results of clinical applicability scoring showed that the consensus had the lowest availability score(64.72％)and the highest acceptability score(76.74％).The results showed that nurses' receiving training and the level of their hospitals were the main influencing factors for scores in various dimensions(P＜0.05).4,774 participants(87.42％)believed that the application of consensus could enhance the standardization of nurses' restraint operations.The safety rate of the restraint consensus was 79.51％,and the economic ratio was 76.87％.Among the evaluators,1,739(22.17％)believed that there were implementation obstacles in the consensus.Conclusion The clinical applicability of the consensus is relatively good,and the application of the consensus helps to improve the standardization of clinical operations.In the future,efforts should be made to strengthen the promotion and training of the consensus,develop hierarchical promotion strategies according to the characteristics of medical institutions,and improve the quality of evidence for the consensus,so as to further enhance the clinical application effect of the consensus.

Objective To investigate the expression of microRNA-508-3p(miR-508-3p)in epithelial ovarian cancer(EOC)tissue,its impact on the migration and invasion of ovarian cancer cells,and its regulatory relationship with zinc-finger E-box-binding homeobox 1(ZEB1).Methods The surgical resection of EOC cancer tissues and paired adjacent normal tissues were collected.SKOV3 cells were divided into the NC mimic group(transfected with NC mimic),miR-508-3p mimic group(transfected with miR-508-3p mimic),si-NC group(transfected with si-NC),si-ZEB1 group(transfected with si-ZEB1)and co-transfection group(co-transfected with si-ZEB1 and miR-508-3p mimic).The mRNA expression levels of miR-508-3p and ZEB1 in EOC cancer tissues,adjacent normal tissues and five groups of cells were measured by real-time quantitative polymerase chain reaction.The Transwell assay was used to detect the cell migration and invasion abilities.Results The relative expression levels of miR-508-3p in EOC tissues and adjacent normal tissues were 0.77±0.36 and 1.07±0.40,the relative expression levels of ZEB1 mRNA in EOC tissues and adjacent normal tissues were 2.10±1.21 and 1.29±0.95,and the differences were statistically significant(all P＜0.01).The migration cell number of the NC mimic,miR-508-3p mimic,si-NC,si-ZEB1 and co-transfection groups was 633.00±32.49,319.20±19.89,650.40±25.85,375.00±17.25 and 129.40±17.10;the invasion cell number was 527.20±25.01,288.60±16.68,520.00±25.83,293.40±18.37 and 76.60±8.76;the relative expression levels of miR-508-3p were 1.05±0.37,3.94±1.21,1.01±0.21,1.26±0.34 and 3.40±0.41;the relative expression levels of ZEB1 mRNA were 1.00±0.04,0.58±0.05,1.00±0.08,0.54±0.07 and 0.29±0.03,respectively.The above indicators showed statistically significant differences between the miR-508-3p mimic group and the NC mimic group,between the si-NC group and the co-transfection group(P＜0.01,P＜0.05).Conclusion MiR-508-3p is lowly expressed in EOC cancer tissue,and it may inhibit the migration and invasion of ovarian cancer cells by targeting ZEB1 expression.