[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

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.

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

Objective:To explore the effects and mechanism of Bushen Tongluo Prescription in mechanical injury of rat endometrium.Method:A total of 60 female SD rats were divided into the blank group, model group, estradiol valerate group, and Bushen Tongluo Prescription group according to the random number table method, with 15 rats in each group. Except for the blank group, the other three groups were used to establish a rat model of endometrial injury using mechanical injury method. After modeling, Bushen Tongluo Prescription group was orally administered with Bushen Tongluo Prescription decoction at a dosage of 2.1 g/kg, the estradiol group was orally administered with estradiol valerate at a dosage of 0.4 mg/kg, and the blank group and model group were orally administered with 0.5% CMC at an equal dosage, once a day, for a total of 8 days. Samples were taken on the 1st, 4th, and 8th day after gastric lavage. The thickness of the endometrium and glands were observed using HE staining, the degree of uterine tissue fibrosis was observed using Masson staining, and VEGF and TGF-β protein and mRNA expressions in uterine tissue were detected using Western blot and fluorescence quantitative PCR.Results:Compared with the Bushen Tongluo Prescription on the first day, the thickness of the endometrium and the number of glands increased on the eighth day ( P<0.05); compared with the model group, the number of glands in the Bushen Tongluo Prescription group increased on the 4th day of administration ( P<0.05), while the fibrotic area of the endometrium decreased on the 8th day of administration ( P<0.05); compared with the model group, on the 8th day of administration, the expression of VEGF protein and TGF-β1 in the Bushen Tongluo Prescription group increased ( P<0.05), and protein expression decreased ( P<0.05); compared with the model group, the group treated with Bushen Tongluo Prescription had TGFβ1 mRNA level on the first day increased ( P<0.05), while the level of TGF-β1mRNA decreased on the 8th day ( P<0.05). Conclusion:Bushen Tongluo Prescription can increase endometrial thickness and receptivity, effectively improve damaged endometrium, anti fibrotic and prevent endometrial adhesion by up-regulating VEGF protein expression and down-regulating TGF-β1 protein and mRNA expression.

Objective To investigate the therapeutic mechanism of Gandou Bushen Decoction(GDBSD)for improving reproductive disorders in male mouse models of Wilson disease(WD).Methods Sixty male homozygous TX mice were randomized equally into 4 groups and treated with daily gavage of saline(WD model group),penicillamine(0.09 g/kg),or GDBSD(0.2 mL/10 g),or with intraperitoneal injection of U0126(20 mg/kg)in addition to GDBSD gavage,with 15 male DL mice as control.After 4 weeks of treatment,copper content in testicular tissue of the mice was detected,and histopathology of the testes and epididymis was examined using HE staining and electron microscopy.TUNEL staining was used to identify apoptotic cells in the testes.The protein expressions of Bcl-2,Cytc,caspase-3,ERK,and p-ERK in the testicular tissue were evaluated with Western blotting,and BrdU-positive cells were detected with immunohistochemical labeling.Sperm density,viability,malformation rate and fertility levels of male mice were studied.Results Treatment with penicillamine and GDBSD obviously improved pathological changes of the testis,increased sperm density and motility,lowered sperm abnormality rate,fertility levels and increased testicular JOHNSEN score of TK mice,but the therapeutic effect of GDBSD was blocked by U0126.GDBSD treatment significantly lowered Cytc and caspase-3 expressions and increased Bcl-2 expression in the testicular tissue of TX mice(P<0.05),while U0126 treatment significantly lowered testicular Bcl-2 expression level.No significant differences were found in total protein expression levels of ERK1/2 among the 5 groups,but p-ERK protein expression was significantly reduced in WD and U0126 groups and increased in penicillamine and GDBSD groups.Conclusion GDBSD can improve spermatogenesis and enhance fertility of male TX mice with WD possibly by activating the ERK signaling pathway to enhance proliferation and reduce apoptosis of the spermatogenic cells.

Purpose::Autologous osteoperiosteal transplantation (AOPT) is one of the most feasible and effective techniques for cystic osteochondral lesions of the talus (OLT). However, few reports have been reported about the process of graft-host bone healing and bone articular surface reconstruction, which help us to further understand the actual situation of bone healing and modify surgical methods.Methods::The case series study retrospectively evaluated 33 osteochondral lesions in 30 patients undertaking AOPT for OLT with subchondral cysts from December 2016 to October 2021. According to CT observation, we used 4 variables to describe the bony articular repair, including the integration of the articular surface, the height of the bone filling, the status of bone union, and the appearance of bone resorption or cystic change. We also analyzed the demographic data and clinical function. Descriptive statistics were used for demographic and clinical variables. Normally distributed data were presented as mean ± SD, and non-normally distributed data were presented as median (Q 1, Q 3). Associations between these variables and the primary clinical outcomes were examined using t-test or one-way ANOVA test for continuous variables. Results::The patients’ mean age was (41.7 ± 14.0) years old and the mean follow-up time was (29.6 ± 17.8) months. The chondral lesion size was (14.3 ± 4.1) mm. The cyst depth was (10.9 ± 3.7) mm. Significant improvements were observed in functional outcomes (according to the numeric rating scale for pain when walking and the American orthopedic foot and ankle society score) between the preoperative and latest follow-up evaluations, from 4.2 ± 2.1 to 2.2 ± 2.0 ( p < 0.001), and from 66.8 ± 12.9 to 83.2 ± 10.4, respectively ( p < 0.001). The overall satisfaction reached 8.3 of 10 points. All patients returned to sports and their median daily steps reached 8000 steps with 27 (81.8%) patients walking over 6000 steps daily. According to CT observation, "discontinuous bony articular surface and gap > 1 mm" was found in 27 grafts (81.8%), and "below the level of the adjacent articular surface, ≤1 mm" in a third of the grafts. Abnormal height of bone filling affected numeric rating scale score ( p=0.049) and American Orthopedic Foot and Ankle Society score ( p =0.027). Of note, bone resorption or cystic changes appeared in up to 13 autografts (39.4%). Conclusions::AOPT is an effective and acceptable technique for cystic OLT. Bone reconstruction is essential for large cystic OLT. How to get better bony articular reconstruction and avoid cyst recurrence should still be paid more attention.