[摘 要] 目的：探索性临床试验初步观察PD-1抑制剂联合脐血NK细胞治疗晚期恶性实体瘤的安全性与疗效。方法：研究对象为2019年12月至2021年12月西安医学院第二附属医院收治的3例晚期实体瘤患者，依据肿瘤类型、参照CSCO指南，采用标准化疗、靶向治疗或贝伐珠单抗联合PD-1抑制剂进行21 d为一疗程的多疗程治疗，期间适时进行脐血NK细胞输注治疗（8 × 107个/次）。每个治疗周期均检测患者靶病灶大小、肿瘤标志物水平、外周血中12种细胞因子水平及淋巴细胞亚群情况，同时评估患者不良反应发生情况。结果：3例患者经PD-1抑制剂联合脐血NK细胞治疗后，2例患者达到疾病稳定（SD；依照RECIST 1.1），其中1例患者持续118 d，另1例患者持续92 d。在NK细胞输注治疗后，患者1肿瘤标志物CA199显著下降到正常值范围内并维持3个随访期，患者2肿瘤标志物CA199、CA242和CA724均出现显著下降。结论：NK细胞与化疗和PD-1抑制剂联合治疗实体瘤具有一定的疗效，本研究中3例患者未出现严重免疫相关不良反应。

This study explores the diagnosis and treatment of needle knife therapy for ankylosing spondylitis (AS) at middle and advanced stage based on the theory of meridian tendons, from a holistic perspective and syndrome differentiation. The treatment strategy includes "harmonizing yin and yang" to address root causes and "tendons-based release" to harmonize qi and blood, with the "tendons nodule points" as the core acupoint selection criterion. Based on this approach, the study systematically elaborates on two needle knife methods for AS: "governor vessel bone-piercing technique" and "below-the-umbilicus release technique", covering indications, acupoint location, and procedures. Clinical case examples are provided to enrich needle knife therapy guided by the theory of meridian tendons, offering insights for clinical and research work on AS.
Humans ; Acupuncture Points ; Acupuncture Therapy/methods* ; Meridians ; Spondylitis, Ankylosing/physiopathology* ; Tendons/physiopathology*

This article aims to explore the effect and mechanism of Liujunzi Pills on the intestinal microbiota of rats with spleen Qi deficiency syndrome. The raw Rhei Radix et Rhizoma water extract(1 g·mL~(-1)) was used to prepare spleen Qi deficiency rat models. A total of 44 SD male rats were randomly divided into a control group, a model group, Liujunzi Pills groups at high(3.24 g·kg~(-1)), medium(1.62 g·kg~(-1)), low(0.81 g·kg~(-1)) doses, and Shenling Baizhu San(2.50 g·kg~(-1)) group. The drug effect was evaluated by observing the following aspects: spleen index, fecal water content, body weight, and intestinal propulsion index. Gut microbiota analysis and 16S rRNA gene sequencing were conducted on feces. Enzyme-linked immunosorbent assay(ELISA) and UV spectrophotometry were used to detect interleukin-1β(IL-1β) and adenosine triphosphate(ATP) levels in small intestine tissues. Hematoxylin-eosin staining and transmission electron microscopy were employed to observe changes in intestinal pathology and microstructure. The results show that, compared with the control group, fecal moisture content is significantly increased while spleen index, body weight, and intestinal propulsion index are significantly reduced in rats of the model group, indicating the successful establishment of the model. The above symptoms can be improved by both Shenling Baizhu San and Liujunzi Pills. Compared with the control group, in the model group, the gut microbiota abundance is changed with an unbalanced development: the abundance of beneficial bacteria within the Bacteroidetes phylum is reduced, accompanied by a significantly decreased Shannon index, and reduced signal levels of nicotinamide adenine dinucleotide phosphate(NADPH)-related enzymes relevant to mitochondria. However, Liujunzi Pills and Shenling Baizhu San can significantly improve the Bacteroidetes phylum abundance in gut microbiota, microbial diversity, and NADPH activity in the model group. Additionally, compared with the control group, the ATP level is decreased and the IL-1β level is increased in small intestinal tissues of the model group, with shorter small intestinal epithelial villi and decreased mitochondrial number. The above symptoms can be improved by Liujunzi Pills and Shenling Baizhu San. In conclusion, Liujunzi Pills can treat spleen Qi deficiency syndrome by enhancing mitochondrial function to regulate gut microbiota balance and diversity.
Animals ; Gastrointestinal Microbiome/drug effects* ; Drugs, Chinese Herbal/pharmacology* ; Male ; Rats, Sprague-Dawley ; Rats ; Qi ; Spleen/metabolism* ; Splenic Diseases/metabolism* ; Humans ; Interleukin-1beta/genetics* ; Bacteria/drug effects* ; Feces/microbiology* ; Adenosine Triphosphate/metabolism*

OBJECTIVE: To observe the clinical efficacy of 3D printing spinal external fixator combined with McKenzie therapy for patients with lumbar dics herniation (LDH). METHODS: Sixty patients with LDH between January 2022 and January 2023 were enrolled. Among them, 30 patients were given McKinsey training. According to different treatment methods, all patients were divided into McKenzie group and McKenzie + 3D printing group, 30 patients in each group. The McKenzie group provided McKenzie therapy. The McKenzie + 3D printing group were treated with 3D printing spinal external fixation brace on the basis of McKenzie therapy. Patients in both groups were between 25 and 60 years of age and had their first illness. In the McKenzie group, there were 19 males and 11 females, with an average age of (48.57±5.86) years old, and the disease duration was (7.03 ±2.39) months. The McKenzie + 3D printing group, there were 21 males and 9 females, with an average age of (48.80±5.92) years old, and the disease duration was(7.30±2.56) months. Pain was evaluated using the visual analogue scale (VAS), and lumbar spine function was assessed using the Oswestry disability index (ODI) and the Japanese Orthopaedic Association (JOA) score. VAS, ODI and JOA scores were compared between two groups before treatment and at 1, 3, 6, 9 and 12 months after treatment. RESULTS: All patients were followed up for 12 months. The VAS for the McKenzie combined with 3D printing group before treatment and at 1, 3, 6, 9, and 12 months post-treatment were(6.533±0.860), (5.133±1.008), (3.933±0.868), (2.900±0.759), (2.067±0.640), (1.433±0.504), respectively. In the McKenzie group, the corresponding scores were (6.467±0.860), (5.067±1.048), (4.600±0.968), (3.533±1.008), (2.567±0.728), (1.967±0.809), respectively. The ODI of the McKenzie group before treatment and at 1, 3, 6, 9, and 12 months post-treatment were (41.033±6.810)%, (37.933±6.209)%, (35.467±6.962)%, (27.567±10.081)%, (20.800±7.531)%, (13.533±5.158)%, respectively. For the McKenzie combined with 3D printing group, the corresponding ODI were(38.033±5.605)%, (33.000±6.192)%, (28.767±7.045)%, (22.200±5.517)%, (17.700±4.836)%, (11.900±2.771)%, respectively. The JOA scores of the McKenzie combined with 3D printing group before treatment and at 1, 3, 6, 9, and 12 months post-treatment were(8.900±2.074), (13.133±2.330), (15.700±3.583), (20.400±3.480), (22.267±3.084), (24.833±2.640), respectively. In the McKenzie group, the corresponding scores were(9.200±2.091), (12.267±2.406), (15.333±3.198), (18.467±2.240), (20.133±2.751), (22.467±2.849), respectively. Before the initiation of treatment, no statistically significant differences were observed in the VAS, ODI, and JOA scores between two groups (P>0.05). At 3, 6, 9, and 12 months post-treatment, the VAS in the McKenzie combined with 3D printing group was significantly lower than that in the McKenzie group, and the difference was statistically significant (P<0.05). The comparison of ODI between two groups at 1, 3, 6, 9, and 12 months post-treatment revealed statistically significant differences (P<0.05). At 6, 9, and 12 months post-treatment, the JOA score in the McKenzie combined with 3D printing group was significantly higher than that in the McKenzie-only group, and the difference was statistically significant (P<0.05). CONCLUSION The combination of 3D printed functional spinal external fixation brace with McKenzie therapy can significantly improve and maintain lumbar function in patients with LDH.
Humans ; Male ; Female ; Middle Aged ; Printing, Three-Dimensional ; Intervertebral Disc Displacement/surgery* ; External Fixators ; Lumbar Vertebrae/surgery* ; Adult ; Braces ; Treatment Outcome

The anterior cingulate cortex (ACC) has recently been proposed as a key player in the representation of itch stimuli. However, to date, little is known about the contribution of specific ACC interneuron populations to itch processing. Using c-Fos immunolabeling and in vivo Ca²⁺ imaging, we reported that both histamine and chloroquine stimuli-induced acute itch caused a marked enhancement of vasoactive intestinal peptide (VIP)-expressing interneuron activity in the ACC. Behavioral data indicated that optogenetic and chemogenetic activation of these neurons reduced scratching responses related to histaminergic and non-histaminergic acute itch. Similar neural activity and modulatory role of these neurons were seen in mice with chronic itch induced by contact dermatitis. Together, this study highlights the importance of ACC VIP⁺ neurons in modulating itch-related affect and behavior, which may help us to develop novel mechanism-based strategies to treat refractory chronic itch in the clinic.
Animals ; Pruritus/physiopathology* ; Vasoactive Intestinal Peptide/metabolism* ; Interneurons/metabolism* ; Gyrus Cinguli/metabolism* ; Mice ; Male ; Mice, Inbred C57BL ; Histamine ; Chloroquine ; Optogenetics ; Mice, Transgenic

The organization of the brain follows a topological hierarchy that changes dynamically during development. However, it remains unknown whether and how cognitive training administered over multiple years during development can modify this hierarchical topology. By measuring the brain and behavior of school children who had carried out abacus-based mental calculation (AMC) training for five years (starting from 7 years to 12 years old) in pre-training and post-training, we revealed the reshaping effect of long-term AMC intervention during development on the brain hierarchical topology. We observed the development-induced emergence of the default network, AMC training-promoted shifting, and regional changes in cortical gradients. Moreover, the training-induced gradient changes were located in visual and somatomotor areas in association with the visuospatial/motor-imagery strategy. We found that gradient-based features can predict the math ability within groups. Our findings provide novel insights into the dynamic nature of network recruitment impacted by long-term cognitive training during development.
Child ; Humans ; Cognitive Training ; Magnetic Resonance Imaging ; Brain ; Brain Mapping ; Motor Cortex

In recent years， the incidence of pulmonary nodules has kept rising. To give full play to the advantages of traditional Chinese medicine （TCM） in the treatment of pulmonary nodules and identify the breakthrough points of integrating TCM with Western medicine， the China Association of Chinese Medicine organized medical experts in TCM and western medicine to carry out in-depth discussion regarding this disease. The discussion encompassed the modern medical advances， TCM theories of etiology and pathogenesis， the role and advantages of TCM in the whole course management of pulmonary nodules， contents and methods of research on pulmonary nodules， and science popularization work， aiming to provide a reference for clinical practice and scientific research. After discussion， the experts concluded that the occurrence of pulmonary nodules was rooted in the deficiency of the lung and spleen and triggered by phlegm dampness， blood stasis， and Qi stagnation. TCM can treat pulmonary nodules by controlling and reducing nodules， improving physical constitution， ameliorating multi-system nodular diseases， reducing anxiety and avoiding excessive diagnosis and treatment， and serving as an alternative for patients who are unwilling or unfit for surgical treatment. At present， the optimal diagnosis and treatment strategy for pulmonary nodules has not been formed， which needs to be further studied from multiple perspectives such as clinical epidemiology， biology， and evidence-based medicine. The primary task of current research is to find out the advantages， effective prescriptions， and target populations and determine the effective outcomes of TCM in the treatment of pulmonary nodules. At the same time， basic research should be carried out to explore the etiology and biological behaviors of pulmonary nodules. The expert consensus on the diagnosis and treatment of pulmonary nodules with integrated TCM and Western medicine needs to be continuously revised to guide clinicians to conduct standardized， scientific， and accurate effective diagnosis and treatment.

Objective To investigate the efficacy and safety of intravenous thrombolysis with low-dose and standard-dose recombinant tissue plasminogen activator(rt-PA)in the elderly patients(aged over 80 years)with acute ischemic stroke(AIS).Methods A total of 201 elderly patients with AIS treated at Tianjin Fourth Central Hospital from February 2019 to February 2023 were prospectively included and randomly assigned to the rt-PA low-dose group(n=93,0.6 mg/kg)and rt-PA standard-dose group(n=108,0.9 mg/kg).The incidence of intra-cranial hemorrhage,symptomatic intracranial hemorrhage,fatal intracranial hemorrhage,neurologic deterioration within 7 days and mortality within 90 days were observed to evaluate the safety.The neurologic improvement rate and good prognosis rate at 90 days were used to evaluate the effectiveness.A stratified analysis of 90-day outcomes was performed based on stroke severity and age.Results The incidence of intracranial hemorrhage,symptomatic intracranial hemorrhage and fatal intracranial hemorrhage within 7 days in rt-PA low-dose group was lower than that in rt-PA standard-dose group(P＜0.05).There were no statistically significant differences between the two groups concerning the residual safety index and the effectiveness index.The 90-day good prognosis rate of moderate stroke sub-group and of≥90 years of age sub-group in rt-PA low-dose group were both higher than that of rt-PA standard-dose group(P＜0.05).Conclusions For AIS patients with moderate stroke and aged over 90 years,intravenous thrombolytic therapy with rt-PA 0.6 mg/kg is recommended.

Objective:This article aimed to explore and establish a systematic, progressive and standardized training content and path for ethics committee members, and also wants to continuously maintain and improve the quality and efficiency of ethical review, and at last wants to provide reference for the future formulation of ethics committee members training direction and system.Methods:This article analyzed the dilemma and the causes in the training process for ethics committee members through literature review, questionnaire survey, and policy researches, and at last focused on exploring the training content, timing, and methods.Results:We should begin with 3 dimensions: the ethics committee and its office, medical institutions, and higher government departments. We should also strengthen the training of ethics committee members through developing training plans, evaluating training effectiveness, improving training content, establishing training systems, reserving training teachers, leveraging the training functions of expert committees, promoting the construction of information exchange platforms, and strengthening international exchanges.Conclusions:It is imperative to strengthen training of ethics committee members, improve their competence, so as to improve the review quality of each ethics committee, and ultimately to safeguard the legitimate rights and interests of research participants.

Objective To investigate the effects of dimethyl itaconate(DMI)on the secretion of pro-inflammatory factors in dendritic cells(DCs)and on the interphotoreceptor retinoid-binding protein(IRBP)1-20-specific T helper 17(Th17)cells in mice with experimental autoimmune uveitis(EAU).Methods Bilateral femur and tibia of C57BL/6J mice were isolated to obtain bone marrow cells,and these bone marrow cells were directionally induced with granulocyte macrophage-colony-stimulating factor(GM-CSF)and interleukin(IL)-4 to differentiate DCs.After 6 days,DCs were ran-domly divided into the DMI group and the phosphate-buffered saline(PBS)group.Cells in the DMI group were pretreated with 250 μmol·L-1 DMI,and cells in the PBS group were pretreated with the same volume of PBS for 3 hours.After-wards,100 μg·L-1 lipopolysaccharide was added in the every group to stimulate cells for 24 hours.The relative mRNA ex-pression levels of IL-6,IL-1 β,and IL-23 in DCs were measured by quantitative real-time polymerase chain reaction(qRT-PCR).The EAU model was constructed by actively immunizing mice with IRBP1-20,Freund's incomplete adjuvant,and my-cobacterium tuberculosis H37RA.Thirteen days after immunization,T cells in the spleen and lymph node isolated from EAU mice were cocultured with DMI-treatedor PBS-treated DCs in the medium containing IRBP1-20.They polarized toward Th17 cells.The percentage of Th17 cells in the cocultured cells was detected by flow cytometry.The IL-17 level in the coculture supernatant was detected by enzyme-linked immunosorbent assay(ELISA).qRT-PCR was performed to detect the relative mRNA expression levels of retinoid-related orphan receptor gamma t(RORγt),IL-17,IL-23R,and GM-CSF in the cocultured cells.Results qRT-PCR analysis revealed that the relative mRNA expression levels of IL-6,IL-1β,and IL-23 in the DMI group were significantly lower thanthose in the PBS group(all P＜0.05).Flow cytometry analysis showed that the proportion of Th17 cells in the cocultured cells in the DMI group was significantly lower than that in the PBS group(P＜0.05).ELISA analysis exhibited that the IL-17 level in the coculture supernatant in the DMI group was significantly lower than that in the PBS group(P＜0.05).The relative mRNA expression levels of IL-17,ROR-γt,IL-23R and GM-CSF in cocultured cells in the DMI group significantly decreased compared with the PBS group(all P＜0.05).Conclusion DMI can reduce the expression of IL-6,IL-1β and IL-23 in DCs,thus negatively modulating the responses of IRBP1-20-specific Th17 cells.