Hua Cao

Autism Spectrum Disorder (ASD) presents a substantial global challenge, yet no pharmacological treatments effectively target its core symptoms, especially in individuals with severe cognitive or adaptive impairments. This double-blind, sham-controlled, randomized clinical trial assessed accelerated intermittent theta burst stimulation (iTBS) targeting the personalized fronto-parietal network (FPN) in ASD. Participants (6–30 years) were randomized in a 2:1 ratio to active or sham iTBS (three daily sessions, 1800 pulses/session) over 12 weeks (324k pulses) alongside behavioral training. The primary outcome was defined as the response rate, charaterized by a ≥ 1-point reduction in ADOS-2 SA at week 12. Of 132 individuals screened, 67 were randomized (mean age 10.04 ± 4.22 years; 88.1% male; all with cognitive/adaptive delays), with 59 completing the study. Active iTBS resulted in a significantly higher response rate (55% vs. 29%) and higher symptom improvement than sham (cohen’s d = −0.53), with mild local pain in only 5% of iTBS group. In the profound autism subgroup, the active group exhibited language improvement alongside amelioration of core symptoms. These findings suggest that prolonged, accelerated FPN-targeted iTBS is a safe and efficacious intervention for severe ASD, offering a promising therapeutic approach. Registration ClinicalTrials.gov Identifier: NCT05890846

Objective: Established perioperative and nursing theories provide foundations for patient safety, adaptation, caring, communication, and professional practice. This study aimed to develop a context‐specific operational framework that applies and specifies these concepts for 5G‐enabled cross‐regional remote surgery, particularly in relation to technology‐mediated care, distributed collaboration, and adaptive nursing capacity. Methods: This mixed‐methods study combined a systematic literature review (four databases; topic search, January 2000‐July 2025; foundational theory searches unrestricted) with case analysis of two cross‐continental, three‐site 5G‐enabled robotic surgeries. The review examined how established nursing theories and perioperative practice guidance have been applied to remote, robotic, and technology‐mediated surgical contexts. Literature synthesis and case analysis were integrated to identify operational domains for framework development. Results: Established nursing theories remained useful conceptual lenses for understanding patient safety, healthcare‐system interaction, adaptation, communication, professional learning, and human responses to technologically advanced care environments. Case analysis did not indicate theoretical obsolescence; rather, it identified areas requiring context‐specific operational specification in remote robotic surgical practice. The AORN perioperative patient‐focused model, Roy’s adaptation model, Benner’s skill acquisition model, and related theories informed the proposed framework. In the two cases, remote nursing involved technological complexity, independent patient‐site teams, and substantial interprofessional coordination. The proposed framework incorporates three interrelated components: (1) technology‐mediated nursing, emphasizing integration of advanced technological systems into nursing judgment and care processes; (2) distributed nursing collaboration, addressing teamwork across geographically separated sites; and (3) nursing adaptive capacity, underscoring continuous learning and flexible response in dynamic technological environments. The preliminary framework may provide guidance for preoperative planning, intraoperative execution, and postoperative care in remote robotic surgery. Implications for Nursing Management: The preliminary framework may inform perioperative nurse managers, nursing directors, and operating room leaders in patient‐site staffing and role allocation, training and competency assessment, standardized communication protocols, emergency drills, quality indicators, and distributed workflow oversight. Conclusion: The framework offers a preliminary, context‐specific operational foundation for cross‐regional remote robotic surgery nursing. It applies, specifies, and supplements established nursing theories rather than replacing them and may support process standardization and care‐quality evaluation. Further multicenter validation, instrument development, and outcome‐based evaluation are needed to refine its applicability.

Background: Emerging evidence suggests that disrupted tryptophan (TRP) metabolism may contribute to an increased risk of neurodevelopmental disorders (NDDs) in the context of maternal inflammation, with gut microbiota playing a pivotal role in regulating TRP metabolic pathways.Methods: Juvenile female rats prenatally exposed to polyriboinosinic-polyribocytidylic acid (Poly I:C) were used to investigate the association between TRP metabolite disturbance and neuropathological/behavioral abnormalities. Behavioral tests assessed anxiety-like behavior, social interaction, and spatial memory. Immunohistochemical and gene expression analyses were performed on the prefrontal cortex (PFC) to evaluate microglial activation and neuroinflammation. TRP-kynurenine (KYN) pathway activity was measured in both PFC and peripheral circulation, along with intestinal TRP metabolism. Gut microbial composition was analyzed through diversity metrics and specific taxa identification.Results: Prenatal Poly I:C exposure induced anxiety-like behavior, impaired social interaction, and spatial memory deficits in offspring. The PFC showed sustained microglial activation and chronic neuroinflammation. TRP-KYN pathway activation was observed in both central and peripheral systems, accompanied by significant disruptions in intestinal TRP metabolism. Gut microbial analysis revealed reduced diversity and specific alterations in TRP-related taxa (Ruminococcus gauvreauii_group and Candidatus Saccharimonas). These microbial changes correlated with both intestinal TRP metabolic levels and behavioral abnormalities.Conclusion: Our findings demonstrate that aberrant TRP metabolism associated with gut microbiota dysbiosis contributes to neuroinflammation and behavioral deficits in offspring following prenatal immune activation, highlighting the gut-microbiota-TRP axis as a key mechanism in neurodevelopmental impairments.

Background: Large number of microRNAs (miRNAs) have been found to be dysregulated in β-thalassemia, but their roles in β-thalassemia are poorly reported. This study aims to investigate the clinical significance of miR-17-3p in β-thalassemia, and to elucidate its regulatory effect on erythropoiesis and γ-globin expression. Methods: We collected peripheral blood samples from 17 patients with β-thalassemia (including intermedia and major subtypes) and 17 healthy controls, and the expression levels of miR-17-3p, BCL11 transcription factor A (BCL11A) and γ-globin were detected by qRT-PCR, and their correlations were analyzed. The regulation of miR-17-3p on BCL11A was evaluated in K562 cells by bioinformatics, luciferase reporter gene assay, fluorescence in situ hybridization and Western blotting. Furthermore, the effects on miR-17-3p overexpression and knockdown on erythropoiesis including cell proliferation, cell cycle, cell apoptosis, and erythroid differentiation of K562 cells were assessed by CCK-8, flow cytometry and benzidine blue staining. Results: The expression of miR-17-3p was upregulated in patients with β-thalassemia, and was positively correlated with fetal hemoglobin (HbF) levels. BCL11A expression was reduced in β-thalassemia patients, and was negatively correlated with miR-17-3p and γ-globin expression. BCL11A was identified as a target gene of miR-17-3p, and was negatively regulated by miR-17-3p. Furthermore, miR-17-3p mediated the upregulation of γ-globin expression in K562 cells through BCL11A. In addition, neither overexpression nor knockdown of miR-17-3p appeared to affect cell proliferation, cell cycle, cell apoptosis or erythroid differentiation of K562 cells in vitro. Conclusion: The upregulated miR-17-3p is associated with HbF in patients with β-thalassemia. Although miR-17-3p does not affect erythropoiesis, it promotes γ-globin expression by targeting BCL11A, suggesting that miR-17-3p may be a promising miRNA for the treatment of β-thalassemia.

Background: This pilot study aimed to characterize the regional distribution of genetic variants associated with autosomal recessive and X-linked recessive (AR/XLR) conditions in Fujian Province, Southeast China, to inform the development of targeted carrier screening programs.Methods: An expanded carrier screening (ECS) panel utilizing next-generation sequencing (NGS) technology was designed to analyze 332 genes associated with 343 AR/XLR conditions. The panel was applied to 440 samples obtained from individuals in Fujian Province. Single nucleotide variants and copy number variations (CNVs) were identified and analyzed using a multidimensional approach that incorporated demographic characteristics, carrier frequencies, and the genetic burden of AR/XLR diseases.Results: A total of 511 variants were detected among the 440 participants, including 43 CNVs (8.41%), affecting 133 genes associated with 123 conditions. The mean number of pathogenic or likely pathogenic variants per sample was 1.16. The highest genetic burden was observed in couples seeking medically assisted reproduction (MAR group), who had histories of fetal loss, second- or third-trimester abnormalities, or postnatal abnormalities. In clinical settings, the percentage of at-risk couples (ARCs) was 6.36% (n = 14), involving seven conditions, with no statistically significant difference in ARC incidence between couples undergoing genetic screening (GS group) and the MAR group. The cumulative carrier rate for 28 genes was ≥1/100. Recurrent variants in GAA, GALT, CYP1B1, and MEFV were identified, exhibiting distinct regional patterns compared to previously reported variants in the Han Chinese population.Conclusion: NGS-based ECS demonstrates significant potential for assessing the genetic burden of AR/XLR conditions and identifying ARCs in Fujian Province. However, before integrating ECS into regional public health initiatives, the development of a region-specific, curated disease panel is necessary to optimize screening efficacy and clinical utility.

Background: End-stage heart and kidney failure is constrained by donor organ scarcity. This study aimed to establish a standardized protocol for combined heart–kidney xenotransplantation using multi-gene–edited porcine grafts in a non-human primate (NHP) model and to evaluate their short-term functional outcomes, providing a basis for future clinical translation. Methods: Genetically modified Bama miniature pigs carrying five gene edits (GTKO/SdaKO/CD46/CD55/TBM) were used as organ donors, and healthy male rhesus macaques served as recipients. Donor hearts and kidneys were harvested using a standardized protocol and preserved via cold perfusion. Cardiac transplantation was performed using an intra-abdominal heterotopic approach, with end-to-side anastomosis between the donor ascending aorta and the recipient abdominal aorta, as well as between the donor pulmonary artery and the recipient inferior vena cava. Renal transplantation involved orthotopic end-to-end anastomosis of the donor renal artery and vein to the recipient's left renal vasculature. A combined immunosuppressive regimen was administered perioperatively, alongside anticoagulation, anti-infective prophylaxis, and supportive care. Recipient vital signs and cardiorenal function were continuously monitored throughout the perioperative period. Experimental endpoints were defined as cessation of renal graft perfusion or irreversible cardiac graft failure. Results: The recipient survived 7 days and 4 hours post-transplant with stable vital signs. Both grafts demonstrated good intraoperative perfusion. The heart graft resumed beating immediately upon reperfusion, with left ventricular ejection fraction peaking at 35% on postoperative day (POD) 5 before declining. Echocardiography revealed myocardial hypertrophy and reduced contractility, but no complete cardiac failure. The kidney graft showed perfusion by POD 1, and urine output by POD 5 confirmed initial function. However, increased vascular resistance and reversed flow between POD 6 and POD 7 indicated acute graft failure. Laboratory assessments showed persistent anemia, lymphopenia, and intermittent prolongation of activated partial thromboplastin time (APTT). At necropsy, the heart graft retained structural integrity and partial function, whereas the kidney graft exhibited hemorrhagic infarction. Notably, vascular anastomoses remained intact throughout the study. Additionally, the heart graft maintained its function despite renal rejection, suggesting greater resilience to immune injury. Conclusion: This combined xenotransplantation model demonstrated short-term graft survival, with the cardiac graft showing greater resistance to rejection than the renal graft. It offers a platform for optimizing clinically viable strategies for long-term functional xenotransplantation.