[摘 要] 目的：探讨异位表达血红蛋白亚基（HBA/HBB）对缺氧条件下嵌合抗原受体T细胞（CAR-T细胞）功能障碍的改善作用及其对肿瘤细胞的杀伤效应。方法：全基因合成技术合成靶向HER2的CAR序列，构建共表达HBA或HBB的CAR慢病毒载体，包装慢病毒后感染人原代T淋巴细胞，制备异位表达HBA/HBB的CAR-T细胞，命名为HBA CAR-T和HBB CAR-T。采用缺氧探针检测小鼠实体瘤缺氧状态。通过流式细胞术检测瘤内CAR-T细胞占比、异位表达血红蛋白亚基的CAR-T细胞阳性率及CAR-T细胞的活性氧、凋亡水平。WB法检测HBA CAR-T和HBB CAR-T内相关血红蛋白亚基表达情况，采用细胞计数板计数检测细胞增殖水平，通过萤光素酶报告基因法检测CAR-T细胞对肿瘤细胞的杀伤能力，qPCR检测CAR-T细胞中缺氧诱导因子-1α（HIF-1α）表达水平，利用MitoXpress Intra试剂盒检测CAR-T细胞内氧气含量。结果：不同细胞构建的实体瘤模型均存在明显缺氧情况，且CAR-T细胞浸润水平与缺氧程度呈显著负相关（P < 0.000 1）。HBA CAR-T与HBB CAR-T构建成功（阳性率 > 60%），相应血红蛋白亚基可稳定表达。缺氧环境下HBA CAR-T和HBB CAR-T的ROS水平、凋亡水平显著下降，增殖、对肿瘤细胞的体外杀伤能力显著强于传统CAR-T细胞（均P < 0.05）。HBA CAR-T与HBB CAR-T内HIF-1α表达降低（均P < 0.001），且缺氧程度显著降低（均P < 0.001）。结论：异位表达血红蛋白亚基可改善缺氧条件下CAR-T细胞功能障碍并增强其对肿瘤细胞的体外杀伤作用。

Primary cilia—those solitary, microtubule-based projections extending from the surface of most eukaryotic cells—are increasingly recognized not merely as cellular appendages, but as sophisticated signaling hubs. By compartmentalizing specific receptors (e.g., GPCRs) and effectors within a microdomain guarded by the transition zone, these organelles function effectively as high-gain sensors capable of integrating mechanical stimuli with metabolic cues. In this review, we examine the pivotal role of primary cilia across the nervous, bone-vascular, and renal landscapes, arguing for a unified “mechano-metabolic coupling” framework. Here, conserved ciliary modules are not static; rather, they are differentially deployed to uphold systemic homeostasis. Within the central nervous system, we position primary cilia as upstream integrators. We highlight how hypothalamic neuronal cilia concentrate metabolic receptors, such as the melanocortin 4 receptor (MC4R), to interpret energy status. Moreover, the recent identification of serotonergic “axon-cilium synapses” points to a direct mode of neurotransmission, wherein 5-HT6 receptors drive nuclear signaling and chromatin accessibility to rapidly modulate gene expression. Through these mechanisms, central cilia modulate sympathetic tone and neuroendocrine output, effectively establishing the mechanical and metabolic “boundary conditions” under which peripheral organs operate. Dysfunction in these central hubs is linked to obesity and neurodevelopmental disorders, including Bardet-Biedl syndrome. In peripheral tissues, cilia serve as versatile mechanotransducers that convert physical forces into biochemical responses. Regarding the bone-vascular system, we discuss the translation of mechanical loads and fluid shear stress into structural remodeling. In osteoblasts, specifically, ciliary integrity is intrinsically linked to cholesterol and glucose metabolism, fine-tuning the balance between Hedgehog and Wnt/β-catenin signaling to govern osteogenesis and bone repair. A similar dynamic exists in the vasculature, where endothelial cilia sense shear stress to modulate KLF4 expression and endothelial-to-mesenchymal transition—processes critical for valvulogenesis and vascular remodeling. Meanwhile, in the kidney, tubular cilia act as terminal effectors within a “shear-cilia-metabolism” axis. Here, fluid shear stress engages ciliary signaling to trigger AMPK-mediated lipophagy and mitochondrial biogenesis, thereby securing the ATP supply required for solute transport. Notably, dysregulation of this axis leads to metabolic reprogramming and aberrant proliferation, acting as a hallmark driver of cystogenesis in polycystic kidney disease (PKD). Crucially, this review attempts to dissect the often-conflated logic of cross-system integration by distinguishing 3 non-equivalent pathways: direct communication via ciliary extracellular vesicles, though this remains largely hypothetical in long-range signaling; “physiology-mediated cascades”, where ciliary dysfunction in a single organ—such as the kidney—precipitates systemic pathology through hemodynamic and metabolic shifts (e.g., altered blood pressure, fluid volume, or uremic toxins); and “parallel molecular defects”, where shared genetic mutations in ubiquitous components like the IFT machinery cause simultaneous, independent failures across multiple organ systems. Building on these distinctions, we propose a nested-loop model that links central set-points with peripheral feedback via physiological variables. Furthermore, we construct a “causality-to-translation” roadmap that pinpoints structural repair (e.g., targeting IFT assembly) and metabolic rescue (e.g., AMPK activation or autophagy induction) as promising therapeutic avenues. Ultimately, this framework provides a theoretical basis for deciphering the shared pathological mechanisms of multisystem ciliopathies, offering a strategic guide for the development of targeted interventions that go beyond symptomatic treatment.

ObjectiveTranscranial focused ultrasound (tFUS) has emerged as a promising noninvasive neuromodulation technique capable of modulating neural activity with high spatial specificity. However, whether tFUS stimulation of the primary somatosensory cortex (S1) can reliably evoke conscious tactile perception without external peripheral sensory input remains unclear. Therefore, this study examined the feasibility of inducing hand-related tactile perception through targeted S1 stimulation and further investigated how sonication duration (SD), a key temporal parameter, influences the consistency of this perceptual response. The findings may provide empirical evidence for optimizing tFUS parameters in human somatosensory modulation. MethodsForty-eight healthy adults participated in the study and were assigned to two experiments. Experiment 1 included 24 participants and was designed to preliminarily examine whether S1-targeted tFUS could evoke hand-related tactile sensations. This experiment comprised two sub-experiments, Experiment 1a and Experiment 1b, with 12 participants in each. Specifically, Experiment 1a used a randomized active stimulation protocol targeting the bilateral S1 to assess the initial feasibility of inducing contralateral tactile perception, whereas Experiment 1b employed an alternating hemispheric design incorporating both active and sham stimulation to verify the specificity of the tFUS-induced sensations. Experiment 2 enrolled another 24 participants and used a real-sham dual-probe design to control for spatial tactile cues that might arise from probe-scalp contact. Five SD levels, including 200, 400, 600, 800, and 1 000 ms, were systematically tested to evaluate how stimulation duration influenced the behavioral response. The primary behavioral outcome was the perceptual consistency rate, quantified according to the accuracy of contralateral tactile localization. ResultsIn Experiment 1, 91.7% of participants reported reliable hand-related tactile sensations during active tFUS stimulation, including numbness, tingling, or similar sensory experiences. Contralateral localization accuracy under active stimulation was significantly higher than the0.50 chance level (P<0.05). In contrast, localization performance under sham stimulation did not differ from chance, suggesting that the observed tactile responses were mainly induced by active S1-targeted tFUS stimulation rather than nonspecific stimulation cues. In Experiment 2, perceptual consistency rates significantly exceeded the chance level under the 400 and 1 000 ms SD conditions(P<0.05), whereas no significant effect was observed at 200, 600, or 800 ms. Pairwise comparisons further showed that the 400 and 1 000 ms conditions produced significantly higher perceptual consistency rates than the 200 ms condition (P<0.05). ConclusiontFUS stimulation of S1 can elicit distinct hand-related tactile sensations without peripheral sensory input, demonstrating the feasibility of using targeted cortical ultrasound stimulation to induce conscious somatosensory perception. The reliability of this perceptual effect was modulated by sonication duration, indicating that temporal stimulation parameters play an important role in shaping both the occurrence and consistency of behavioral responses. Among the tested conditions, 400 ms appeared to provide a favorable temporal window for generating stable tactile perception, whereas excessively short stimulation may be insufficient to produce consistent responses. These findings highlight the sensitivity of somatosensory networks to ultrasonic modulation and provide useful parameter guidance for the application of tFUS in noninvasive sensory enhancement and cortical functional mapping.

A nodule in the right middle lobe of the lung was treated by a combination of cone-beam CT,three-dimensional registration for fusion imaging,and electromagnetic navigation bronchoscopy-guided thermal ablation.The procedure lasted for 90 min,with no significant bleeding observed under the bronchoscope.The total radiation dose during the operation was 384 mGy.The patient recovered well postoperatively,with only a small amount of blood in the sputum and no pneumothorax or other complications.A follow-up chest CT on the first day post operation showed that the ablation area completely covered the lesion,and the patient was discharged successfully.
Humans ; Bronchoscopy/methods* ; Catheter Ablation/methods* ; Cone-Beam Computed Tomography ; Electromagnetic Phenomena ; Imaging, Three-Dimensional ; Lung Neoplasms/diagnostic imaging* ; Tomography, X-Ray Computed

Cilia,as cellular sensory organelles,actively partici-pate in and regulate cellular processes such as autophagy and metabolic breakdown during their generation and transportation.Autophagy,on the other hand,is a cell self-protection mecha-nism that maintains cellular homeostasis by clearing aggregates and damaged organelles.Combining recent research findings,this review comprehensively elucidates the bidirectional crosstalk between primary cilia and autophagy.Specifically,it highlights the crucial role of cilia-dependent signaling pathways in activa-ting cellular autophagy and how autophagy regulates cilia genera-tion and length by degrading specific ciliary proteins.Moreover,the dysregulation of primary cilia and autophagy is closely asso-ciated with the clinical manifestations and pathogenesis of vari-ous ciliopathy-related diseases such as polycystic kidney disease and tuberous sclerosis.In terms of pharmacotherapy,this review provides a comprehensive and in-depth overview of small mole-cule inhibitors targeting ciliogenesis,including cytoskeletal drugs and Hedgehog signaling pathway inhibitors.Despite the current limitations in clinical use,these drugs lay the groundw-ork for developing highly specific targeted small molecule inhibi-tors of ciliogenesis and for the treatment of ciliopathies and canc-ers.By systematically discussing ciliogenesis,autophagy,disea-ses and drugs,this review offers new insights for further elucida-ting the crosstalk between ciliogenesis and autophagy,exploring their pathological mechanisms in disease development,and de-veloping therapeutic strategies in the future.

Objective To investigate the efficacy of continuous suture and parachute continuous suture in forearm autologous arteriovenous endovascular fistula surgery,and to analyse their effects on postoperative fistula patency rate and complications.Methods 209 patients with end-stage renal disease(ESRD)admitted to our hospital from January,2020 to January,2024 were selected as observation objects,and they were divided into group A(simple intermittent suture,n=50),group B[simple continuous(two-point)suture,n=63]and group C(parachute continuous suture,n=96)The postoperative vascular anastomosis time,operation time,blood flow,vascular patency rate,thrombosis rate,complication rate and quality of life score of each group were compared.Results In group C,the vascular anastomosis time and overall operation time were the shortest,and the blood flow was less(P<0.05),but there was no significant difference in vascular patency rate,thrombosis rate and complication rate(P>0.05).In group C,the level of serum inflammatory factors decreased the most and the qual-ity of life improved the most significantly(P<0.05).Conclusions Continuous suture and parachute suture can shorten the operation time,reduce the level of serum factors and improve the quality of life.The best scheme should be selected according to the individual differences of patients.

OBJECTIVE: To investigate the effects of acupuncture on the neurotransmitter levels and gut microbiota in a mouse model of Tourette syndrome (TS). METHODS: Thirty-six male C57/BL6 mice were randomly divided into 4 groups using a random number table method: 3,3'-iminodipropionitrile (IDPN) group, control group, acupuncture group, and tiapride group, with 9 mice in each group. In the IDPN group, acupuncture group, and tiapride group, mice received daily intraperitoneal injections of IDPN (300 mg/kg body weight) for 7 consecutive days to induce stereotyped behaviors. Subsequently, in the acupuncture intervention group, standardized acupuncture treatment was administered for 14 consecutive days to IDPN-induced TS model mice. The selected acupoints included Baihui (DU 20), Yintang (DU 29), Waiguan (SJ 5), and Zulinqi (GB 41). In the tiapride group, mice were administered tiapride (50 mg/kg body weight) via oral gavage daily for 14 consecutive days. The control group, IDPN group, and acupuncture group received the same volume of saline orally for 14 consecutive days. Stereotypic behaviors were quantified through behavioral assessments. Neurotransmitter levels, including dopamine (DA), glutamate (Glu), and aspartate (ASP) in striatal tissue were measured using enzyme-linked immunosorbent assay. Dopamine transporter (DAT) expression levels were additionally quantified through quantitative polymerase chain reaction (qPCR). Gut microbial composition was analyzed through 16S ribosomal RNA gene sequencing, while metabolic profiling was conducted using liquid chromatography-mass spectrometry (LC-MS). RESULTS: Acupuncture administration significantly attenuated stereotypic behaviors, concurrently reducing striatal levels of DA, Glu and ASP concentrations while upregulating DAT expression compared with untreated TS controls (P<0.05 or P<0.01). Comparative analysis identified significant differences in Muribaculaceae (P=0.001), Oscillospiraceae (P=0.049), Desulfovibrionaceae (P=0.001), and Marinifilaceae (P=0.014) following acupuncture intervention. Metabolomic profiling revealed alterations in 7 metabolites and 18 metabolic pathways when compared to the TS mice, which involved various amino acid metabolisms associated with DA, Glu, and ASP. CONCLUSIONS Acupuncture demonstrates significant modulatory effects on both central neurotransmitter systems and gut microbial ecology, thereby highlighting its dual therapeutic potential for TS management through gut-brain axis regulation.
Animals ; Tourette Syndrome/metabolism* ; Gastrointestinal Microbiome ; Neurotransmitter Agents/metabolism* ; Acupuncture Therapy ; Male ; Mice, Inbred C57BL ; Mice

OBJECTIVES: To explore the risk factors for malnutrition in patients with ulcerative colitis complicated with pyoderma gangrenosum and establish a nutritional risk prediction model for these patients. METHODS: A total of 277 patients with ulcerative colitis complicated with pyoderma gangrenosum treated from 2019 to 2024 were divided into malnutrition group (n=185) and normal nutrition group (n=92) according to whether malnutrition occurred. The data of 25 potential related factors pertaining to general demography, living and eating habits, and disease-related data were compared between the two groups. Lasso regression was used to screen the risk factors, and a nomogram model was established based on the screened factors and its prediction performance was assessed. RESULTS: The patients in the malnutrition group and normal nutrition group showed significant differences in 21 factors including gender, age, education level, BMI, place of residence, course of disease, and SAS language score (P<0.05). Lasso regression analysis identified 6 factors associated with malnutrition in these patients, namely the duration of ulcerative colitis, activity of ulcerative colitis, duration of pyoderma gangrenosum, number of chronic diseases, SAS score, and sleep quality. The nomogram prediction model established based on these 6 factors had an AUC of 0.992 (95% CI: 0.984-1.000) for predicting malnutrition in these patients, and its application in 14 clinical cases achieved an accuracy rate of 100%. CONCLUSIONS The duration of ulcerative colitis, activity of colitis, duration of pyoderma gangrenosum, number of chronic diseases, anxiety, and sleep quality are closely related with malnutrition in patients with ulcerative colitis complicated by pyoderma gangrenosum, and the nomogram prediction model based on these factors can provide assistance for predicting malnutrition in these patients.
Humans ; Colitis, Ulcerative/complications* ; Malnutrition/etiology* ; Risk Factors ; Pyoderma Gangrenosum/complications* ; Female ; Male ; Adult ; Nomograms ; Middle Aged ; Nutritional Status ; Regression Analysis

Apical microsurgery is accurate and minimally invasive, produces few complications, and has a success rate of more than 90%. However, due to the lack of awareness and understanding of apical microsurgery by dental general practitioners and even endodontists, many clinical problems remain to be overcome. The consensus has gathered well-known domestic experts to hold a series of special discussions and reached the consensus. This document specifies the indications, contraindications, preoperative preparations, operational procedures, complication prevention measures, and efficacy evaluation of apical microsurgery and is applicable to dentists who perform apical microsurgery after systematic training.
Microsurgery/standards* ; Humans ; Apicoectomy ; Contraindications, Procedure ; Tooth Apex/diagnostic imaging* ; Postoperative Complications/prevention & control* ; Consensus ; Treatment Outcome

Pulpotomy, which belongs to vital pulp therapy, has become a strategy for managing pulpitis in recent decades. This minimally invasive treatment reflects the recognition of preserving healthy dental pulp and optimizing long-term patient-centered outcomes. Pulpotomy is categorized into partial pulpotomy (PP), the removal of a partial segment of the coronal pulp tissue, and full pulpotomy (FP), the removal of whole coronal pulp, which is followed by applying the biomaterials onto the remaining pulp tissue and ultimately restoring the tooth. Procedural decisions for the amount of pulp tissue removal or retention depend on the diagnostic of pulp vitality, the overall treatment plan, the patient's general health status, and pulp inflammation reassessment during operation. This statement represents the consensus of an expert committee convened by the Society of Cariology and Endodontics, Chinese Stomatological Association. It addresses the current evidence to support the application of pulpotomy as a potential alternative to root canal treatment (RCT) on mature permanent teeth with pulpitis from a biological basis, the development of capping biomaterial, and the diagnostic considerations to evidence-based medicine. This expert statement intends to provide a clinical protocol of pulpotomy, which facilitates practitioners in choosing the optimal procedure and increasing their confidence in this rapidly evolving field.
Humans ; Calcium Compounds/therapeutic use* ; Consensus ; Dental Pulp ; Dentition, Permanent ; Oxides/therapeutic use* ; Pulpitis/therapy* ; Pulpotomy/standards*