[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

Objective:To investigate the correlation between non-Hodgkin lymphoma (NHL) and chronic hepatitis B virus (HBV) infection by using the method of two-sample bidirectional Mendelian randomization (MR) analysis.Methods:Genetic variation data for NHL came from the Finnish database (FinnGen) Consortium 2021 public genome-wide association study (GWAS) dataset including 1 088 patients with NHL and 299 952 control subjects. The GWAS dataset for chronic HBV infection was derived from GWAS analysis published in 2021, including 145 NHL patients and 351 740 control subjects. NHL was used as an exposure factor, single nucleotide polymorphism (SNP) significantly associated with NHL was used as an instrumental variable (IV), chronic HBV infection was used as an outcome variable. The two-sample MR analysis was performed by using inverse-variance weighted (IVW) method. Chronic HBV infection was taken as an exposure factor, SNP significantly associated with chronic HBV infection was taken as IV, and NHL was taken as outcome variable, and then reverse two-sample MR analysis was performed. The IVW method used the inverse variance of each IV as the weight to fit, and the ratio method was used to measure SNP one by one and make weighted regression analysis, so as to obtain the overall estimate. MR-Egger regression and the weighted median (WME) method were also used to supplement the IVW method. In sensitivity analysis, leave-one-out sensitivity analysis was used to evaluate the impact of a single SNP. Cochran Q test was used to analyze the heterogeneity of the selected IV. MR-Egger regression was used to measure the average horizontal pleiotropy of IV, and the P-value of directivity was calculated. The MR-pleiotropy residual sum and outlier (MR-PRESSO) Global Test was used to exclude possible horizontal pleiotropic outliers and reduce bias. Results:In the leave-one-out sensitivity analysis, SNP with significant effects on causal associations was excluded. In forward MR analysis, IVs were 10 SNPs associated with NHL; the IVW method indicated that there was no causal association between NHL and chronic HBV infection ( OR = 0.979, 95% CI: 0.925-1.036, P = 0.465). MR-Egger regression ( OR = 0.992, 95% CI: 0.926-1.062, P = 0.825) and WME method ( OR = 0.992, 95% CI: 0.934-1.055, P = 0.805) were used as supplementary methods to obtain the consistent results. In sensitivity analysis, Cochran Q test showed no heterogeneity among IVs (IVW method: P = 0.271, MR-Egger regression: P = 0.239). Horizontal pleiotropy was not found in the MR-Egger regression (intercept was -0.01, P = 0.778) and the MR-PRESSO Global Test ( P > 0.05), suggesting robust results. In the reverse MR analysis, IVs were 8 SNPs associated with NHL; the IVW method ( OR = 1.117, 95% CI: 0.942-1.324, P = 0.202) also found no significant causal relationship between chronic HBV infection and NHL; MR-Egger regression ( OR = 0.777, 95% CI: 0.450-1.343, P = 0.401) and WME method ( OR = 1.120, 95% CI: 0.887-1.415, P = 0.351) also showed similar risk estimates. Sensitivity analysis also suggested the consistency and reliability of the results. Cochran Q test showed no heterogeneity among IVs (IVW method: P = 0.775, MR-Egger regression: P = 0.903). Horizontal pleiotropy was not found by MR-Egger regression (intercept was 0.102, P = 0.548) and MR-PRESSO Global Test ( P > 0.05). Conclusions:MR analysis suggests no causal relationship between NHL and chronic HBV infection.

Objective To investigate the efficacy and safety of regional citrate anticoagulation(RCA)in continuous blood purification(CBP)treatment during the shock and infection phases of severe burns.Methods A retrospective analysis was conducted on the clinical data of 64 patients who received RCA-CBP treatment at the Burns Reseaich Institute,the First Affiliated Hospital of Army Medical University from Jan-uary 2015 to January 2024.The patients were divided into the burn shock phase(burn duration<2 days,n=18)and the burn infection phase(burn duration≥2 days,n=46)according to the start time of CBP treat-ment.General datas,total body surface area burned(TBSA),abbreviated burn severity index(ABSI),hemato-crit(HCT)at the start of CBP treatment,platelet count(PLT),activated partial thromboplastin time(APTT),serum creatinine,urea nitrogen,total bilirubin,acute physiology and chronic health evaluation Ⅱ(APACHEⅡ)score,sequential organ failure assessment(SOFA)score,Child-Pugh score,filter usage time for each CBP treatment,the incidence of unplanned treatment termination,blood gas analysis,and adverse e-vents were compared between the two groups.Results Compared with the burn shock phase,the levels of HCT and PLT in the burn infection phase were lower,the levels of urea nitrogen and the incidences of shock,hyperlactatemia and hypoxemia were higher,the filter usage time was longer,and the incidence of unplanned treatment termination was lower,the differences were statistically significant(P<0.05).The results of mult-ivariate COX regression analysis showed that the burn shock phase was a protective factor for the filter usage time(P<0.05).Among the 64 patients,citrate accumulation occurred in 2 patients(3.1%),both of which were septic shock combined with hyperlactatemia during the burn infection stage.Patients with acid-base im-balance and electrolyte disorder were corrected after adjusting the treatment.There were 5 new bleeding e-vents,all of which were caused by the primary diseases.Conclusion RCA is safe and effective for CBP treat-ment in severe burned patients and can be used as a routine anticoagulant method.

Objective To investigate the influence of preoperative blood lipid levels on postoperative recovery in patients with acute Achilles tendon rupture(AATR).Methods The clinical data of 353 AATR patients treated in Department of Orthopaedics Trauma of our hospital from Jan.2021 to Jan.2024 were retrospectively analyzed,including general clinical information and preoperative fasting blood biochemistry indices.Patients'Achilles tendon total rupture score(ATRS)and American Orthopaedic Foot and Ankle Society(AOFAS)ankle-hindfoot score were recorded 6 months postoperatively.Postoperative recovery was categorized as favorable if ATRS≥80 and poor if ATRS＜80;similarly,recovery was considered favorable if AOFAS score≥90 and poor if AOFAS score＜90.Univariate and multivariate logistic regression analyses were done to investigate the influencing factors of patients'postoperative recovery.Results When categorized by ATRS,patients in the favorable postoperative recovery group exhibited significantly lower serum levels of triglyceride(TG),total cholesterol(TC),and low-density lipoprotein(LDL)compared to the poor postoperative recovery group(all P＜0.05).Similarly,when categorized by AOFAS score,the favorable postoperative recovery group had lower serum TG and TC levels than the poor postoperative recovery group(both P＜0.05).Univariate logistic regression analysis demonstrated that in the ATRS grouping,elevated serum levels of TG,TC and LDL were significantly associated with an increased risk of poor postoperative recovery in AATR patients(all P＜0.05).Similarly,in the AOFAS score grouping,elevated serum levels of TG and TC were significantly correlated with an increased risk of poor postoperative recovery in AATR patients(both P＜0.05).Multivariate logistic regression analysis further identified that high serum LDL level was an independent predictor of poor postoperative recovery in AATR patients(P＜0.05).Conclusion High preoperative serum LDL level is associated with an increased risk of poor postoperative recovery in AATR patients.Therefore,preoperative blood lipid management in AATR patients may have positive effects on postoperative functional recovery.

Standardized clinical trial reporting is crucial for ensuring the scientific validity,reproducibility,and clinical translational value of reported results.The Consolidated Standards of Reporting Trials(CONSORT)statement,an internationally recognized guideline for randomized controlled trials(RCTs),has become an important reference standard for writing research papers in medicine since the 2010 version of CONSORT was published.With advancements in scientific research methodologies and the emergence of new forms of clinical trials,the CONSORT working group released an updated version in April 2025,published in journals such as The BMJ.Herein,we provide a systematic interpretation of the core revisions of CONSORT 2025,as well as a comparison with CONSORT 2010 to highlight the key differences.By providing practical,example-based recommendations,we aim to help domestic researchers apply the new guidelines efficiently,thereby improving the quality of clinical trial reports authored by domestic researchers.

A high-quality clinical trial protocol is the cornerstone for ensuring the scientific integrity and ethical compliance of a study.The Standard Protocol Items:Recommendations for Interventional Trials(SPIRIT)has become the international benchmark for developing clinical trial protocols since its release in 2013.To adapt to the developing trends of open science and patient-centered principles,the SPIRIT group completed a comprehensive update in 2025.While retaining its core structure,this updated guideline introduces a new open science module and incorporates several new elements,including patient and public involvement,trial monitoring,and data sharing,alongside substantial revisions of five pre-existing items.In this article,we critically examine the core revisions in SPIRIT 2025 and,through analysis of representative case studies,illustrate the practical application of the new reporting guideline in drafting trial protocols.Our goal is to to provide Chinese researchers with a valuable reference for understanding and implementing this new reporting guideline,thereby enhancing the quality and rigor of clinical trial protocols developed in the country.