[摘 要] 目的：探索淋巴细胞亚群对非小细胞肺癌（NSCLC）患者接受程序性死亡受体1（PD-1）单抗联合化疗的疗效预测及预后评估的价值。方法：回顾性分析2022年1月至2023年12月在兰州大学第二医院确诊的接受PD-1单抗联合化疗的50例NSCLC患者的临床资料，收集患者治疗前及治疗2周期后的外周血淋巴细胞亚群（包括总T细胞、CD4+ T细胞、CD8+ T细胞、NK细胞、总B淋巴细胞、CD4+/CD8+ T细胞比值等）的数据。治疗2周期后进行影像学检查评价治疗的疗效，分为疾病控制（DC）组和疾病进展（PD）组。使用卡方检验、秩和检验和Logistic回归分析淋巴细胞亚群表达水平与NSCLC患者近期疗效的关系，采用Kaplan-Meier法分析无进展生存期（PFS）预测疗效的价值。结果：PD-1单抗联合化疗对NSCLC患者的免疫状态产生了显著影响，接受免疫联合化疗后，患者外周血CD4+ T细胞、CD4+/CD8+ T细胞比值均显著升高（均P < 0.01），CD8+ T细胞下降。近期疗效显示，DC组患者血清CD4+ T细胞比例及CD4+/CD8+ T细胞比值均高于PD组（均P < 0.01）。Logistic多因素分析显示，CD4+/CD8+ T细胞比值是PD-1单抗联合化疗疗效的独立影响因素。通过ROC曲线分析，CD4+/CD8+ T细胞比值变化量AUC为0.820 > 0.5，截断值为0.15，CD4+/CD8+ T细胞比值变化量 ≥ 0.15的患者的PFS更长。结论：晚期NSCLC患者外周血中CD4+ T细胞和CD8+ T细胞比例、CD4+/CD8+ T细胞比值可以预测PD-1单抗联合化疗的疗效和预后。

Objective: To investigate the status of salt-restriction spoons use among residents in Zhejiang Province, so as to provide evidence for optimizing salt-reduction intervention strategies and preventing chronic disease. Methods: Residents aged 18-69 from five counties (cities/districts) in Zhejiang Province were selected using a multi-stage stratified random sampling method. Demographic characteristics, dietary habits, and salt-restriction spoons use were collected using questionnaires. The rate of salt-restriction spoons use and correct rate of salt-restriction spoons use were analyzed. Factors affecting salt-restriction spoons use among residents were analyzed by multivariable logistic regression model. Results: Totally 7 601 questionnaires were allocated, and 7 509 valid questionnaires were recovered, with an effective recovery rate of 98.79%. The respondents included 3 744 males (49.86%) and 3 765 females (50.14%). The mean age was (44.81±14.03) years. The rate of salt-restriction spoons use was 11.97%, the correct rate of salt-restriction spoon use was 52.73%. Multivariable logistic regression analysis showed that rural (OR=0.851, 95%CI: 0.731-0.991), education level of primary school and below (illiterate or semi-literate, OR=0.269, 95%CI: 0.172-0.420; primary school, OR=0.595, 95%CI: 0.436-0.811), and excessive dietary salt intake (OR=0.718, 95%CI: 0.559-0.922) were inhibiting factors for salt-restriction spoons use among residents; physical exercise (OR=1.581, 95%CI: 1.362-1.836) and received health education on a low-salt diet (OR=2.082, 95%CI: 1.790-2.421) were promoting factors for salt-restriction spoons use among residents. Conclusions The rate of salt-restriction spoons use among residents in Zhejiang Province was relatively low, primarily influenced by region, educational level, physical activity, dietary salt intake, and health education on a low-salt diet. It is recommended that propose a multi-component intervention strategy centered on skill enhancement and health education, delivered through progressive staged implementation, to promote sustained adoption of salt-restriction spoons among residents.

Morita therapy has been bom for more than 100 years.Inpatient Morita therapy is highly oper-able and easy to master.It can improve many refractory neuroses through four-stage treatment.But more neuroses are treated in outpatient clinics,and Morita therapy cannot be used in hospitalized patients.Therefore,the formula-tion of expert opinions on outpatient operations is particularly important.This paper is based on domestic and for-eign references,and after many discussions by domestic Morita therapy experts,and then drew up the first version of the expert opinions on operation of outpatient Morita therapy.Meanwhile the operation rule of Morita therapy in three stages of outpatient treatment was formulated:in the etiological analysis stage,under the theoretical guidance of Morita therapy,analyze the pathogenic factors,to improve treatment compliance and reduce resistance;during the operating stage,guide patients to engage in constructive and meaningful actions,realizing the achievement of letting nature take its course principle;in the cultivating character and enriching life stage,pay attention to positive infor-mation,expanding the scope and content of actions,improving the ability to adapt to complex life,and preventing recurrence caused by insufficient abilities.It will lay a foundation for the promotion of Morita therapy in domestic outpatient clinics,so that more patients with neurosis and other psychological diseases could receive characteristic Morita therapy treatment in outpatient clinics.

BACKGROUND:In recent years,High-definition transcranial direct current stimulation(HD-tDCS)has garnered significant attention due to its potential non-invasive modulation of brain function.However,there is still a lack of visual analysis in the literature regarding this technique. OBJECTIVE:To perform a visual analysis of HD-tDCS-related research so as to explore the current status and trends in this field. METHODS:English literature related to HD-tDCS was retrieved from the Web of Science Core Collection database covering the period from January 1,2010 to May 6,2023.The VOSviewer software was used to visualize and analyze the source journals,countries/regions,authors,institutions,cited references,and keywords of the included literature,creating a knowledge map to uncover the research landscape and hotspots. RESULTS AND CONCLUSION:A total of 336 articles were included,showing a consistent increase in the annual publication count of HD-tDCS research.Among these,the United States contributed the highest number of publications(141 articles)with 4 221 citations,followed by China with 70 articles and 401 citations.Brain Stimulation was the most prolific journal(28 articles),Marom Bikson was the most productive author(37 articles),and The City College of New York was the most active institution(35 articles).The most frequently mentioned keywords in the field included motor cortex,regulation,working memory,excitability,and dorsolateral prefrontal cortex.Notable recent keywords in the last 5 years include attention-deficit/hyperactivity disorder,brain networks,and stimulation intensity.Currently,the volume of HD-tDCS research is relatively limited,but is on an upward trajectory,indicating substantial research potential.It is expected that future studies in this domain will continue to focus on the application of HD-tDCS in cognitive and neuropsychiatric disorders,while also exploring its therapeutic mechanisms targeting the motor cortex and dorsolateral prefrontal cortex based on brain network analysis.

BACKGROUND:The abnormal gait of stroke patients seriously affects their propulsive force during walking,which subsequently reduces their walking speed,walking distance,and stability,increases their risk of falls,and seriously affects their quality of life. OBJECTIVE:To review the relevant research on propulsive force deficits in stroke patients with hemiplegia,to summarize the understanding of existing researchers on propulsive force deficits,to analyze the relationship between propulsive force and gait,and finally to explain and compare the latest rehabilitation technologies used to improve propulsive force deficits,providing reference for clinical treatment. METHODS:Relevant literature was retrieved from WanFang,CNKI,PubMed,and Web of Science Core Collection through computer search.The Chinese and English search terms were"propulsive force OR propulsive,stroke OR cerebral infarction OR hemiplegia,walk* OR gait."The search time limit was from 2003 to 2023,and 71 articles were finally included for review and analysis. RESULTS AND CONCLUSION:Training targeting the hip and ankle joints may be more effective for patients'walking function,especially training with the application of flexible exoskeleton robots,but more sufficient evidence is still needed to use propulsion as a prognostic indicator of walking function in stroke patients.Biomechanical variables related to propulsive force include:the hip joint extension angle at terminal stance,ankle joint dorsiflexion torque,and knee joint extension.Damage to the corticospinal tract,cerebellar-cortical pathways,and the reticulospinal tract in hemiplegic patients are associated with reduced propulsive force and gait asymmetry.Propulsive force is crucial for the stability of healthy gait,and a decrease in propulsive force is unfavorable for gait stability.Gait symmetry is correlated with propulsive force,stride length symmetry,trunk displacement,and lower limb swing ability,with propulsive force being a key factor.Propulsive force can serve as a quantitative indicator for assessing the gait of hemiplegic patients,and evaluation of gait using propulsive force is beneficial for the long-term development of walking ability.Main rehabilitation techniques for improving propulsive force include:lower limb exoskeleton robot walking training,treadmill training combined with functional electrical stimulation,adaptive speed treadmill training,biofeedback technology,and whole-body vibration training.Among them,whole-body vibration training and biofeedback technology are more effective.The specific contributions and mechanisms of the hip,knee,and ankle joints in improving propulsive force are still controversial,but it is expected that the contributions of the hip and ankle joints are greater.Focusing on the improvement of propulsive force as a rehabilitation goal may yield more sustainable advancements in walking function.However,several current challenges persist in this field:understanding the neurobiological basis of propulsive force deficits in stroke patients,assessing the long-term efficacy of current rehabilitation techniques for enhancing propulsive force,and determining the most suitable patient populations for the application of major rehabilitation techniques aiming at improving propulsive force.These areas require further exploration by subsequent researchers.

Objective:To determine the motion detection uncertainty of the real-time CybeRay ? imaging system and patient intrafractional motion with thermoplastic mask-based immobilization. Methods:Real-time CybeRay ? imaging system was used for irradiation and treatment for head phantom and patients with brain tumors. All patients were immobilized with thermoplastic masks. Real-time imaging was delivered using kilovoltage projection images during radiotherapy. The detected patient motion data was collected from 5 head phantom measurements and 27 treatment fractions of 9 brain tumor patients admitted to Kaifeng Cancer Hospital. The accuracy and uncertainty of the motion monitoring system were determined. Results:The mean and standard deviation (SD) of the detected motion in the X, Y, and Z directions for phantom were (-0.02±0.41) mm, (-0.05±0.22) mm and (0.01±0.35) mm, respectively. The detected motion in the X, Y and Z directions for patents were (-0.13±0.48) mm, (-0.05±0.48) mm and (0.11±0.36) mm, respectively. After removing the motion detection uncertainty, the actual intrafractional motion of patients were (-0.11±0.25) mm, (0±0.43) mm and (0.10±0.08) mm in three directions, respectively. Conclusions:The uncertainty of real-time imaging-based motion monitoring system of CybeRay ? is less than 0.5 mm. It is feasible to apply thermoplastic masks for brain tumor patients in clinical practice, which can provide steady immobilization and limit the SD of patient intrafractional motion within 0.5 mm. Real-time imaging-based motion monitoring system of CybeRay ? is accurate for patient motion monitoring during frameless stereotactic radiosurgery/radiotherapy.

Objective:To develop the anti-CD30 monoclonal antibody 64Cu-1, 4, 7-trizacyclononane-1, 4, 7-triacetic acid (NOTA)-CD30 and visualize CD30 expression in lymphoma non-invasively. Methods:The CD30 expression levels of 5 cell lines (Karpas299, Raji, Daudi, Ramos, and U266) were assessed by Western blot. Cell lines with high and low CD30 expression were selected for flow cytometry to evaluate the specific binding affinity of anti-CD30 monoclonal antibody. Thirteen NSG mice were used to established CD30 positive and negative subcutaneous xenograft models. 64Cu-NOTA-CD30 was obtained and 64Cu-NOTA-immunoglobulin (Ig)G was used as the control. ImmunoPET imaging was performed 2, 24, and 48 h after the injection of 64Cu-NOTA-CD30 or 64Cu-NOTA-IgG. Finally, the biodistribution studies were conducted. Repeated-measures analysis of variance and Bonferroni test were conducted for comparison. Results:Karpas299 showed the highest CD30 expression, while Raji showed the lowest. Flow cytometry showed specific binding affinity of the anti-CD30 monoclonal antibody to the Karpas299 cell line. The radiochemical purities of the probes were both higher than 95%. In microPET, the 64Cu-NOTA-CD30 uptake of Karpas299 xenograft tumors increased over time, with (11.46±0.58), (17.60±1.16) and (19.46±0.99) percentage activity of injection dose per gram of tissue (%ID/g) at 2, 24 and 48 h respectively. The contrast to normal tissue was good at 48 h, with the tumor/heart (blood) ratio of 2.20±0.22. The uptake of 64Cu-NOTA-CD30 in Karpas299 tumor at 48 h after injection was significantly higher than that in Raji tumor ((6.10±1.03) %ID/g) and 64Cu-NOTA-IgG in Karpas299 tumor ((5.12±0.89) %ID/g; F=290.99, t values: 19.65 and 22.25, all P<0.001). The uptake of 64Cu-NOTA-CD30 and the control probe in the heart and liver decreased over time in all groups. Ex vivo biodistribution at 48 h was mainly consistent with the results of microPET in vivo. Conclusions:64Cu-NOTA-CD30 is able to visualize the expression level and distribution of CD30 non-invasively. It is promising to be applied for screening the beneficial groups and evaluating efficacy for CD30-targeted immunotherapy.

Objective To investigate the clinical and pathological features of progressive familial intrahepatic cholestasis type 3 (PFIC3). Methods A retrospective analysis was performed for 1326 patients with unexplained liver disease who attended Nanjing Second Hospital from January 2017 to December 2019, among whom 8 patients were diagnosed with PFIC3 based on clinical/pathological manifestation and gene sequencing results (1 patient did not undergo liver biopsy due to contraindication). Clinical, laboratory, imaging, and pathological findings were analyzed and a literature review was performed for the pathology of ABCB4-related diseases to summarize the clinical and pathological features of PFIC-3. Results Among the 8 patients with PFIC3, there were 5 male patients and 3 female patients, with a median age of 29.5 years. Of all 8 patients, 4 (50%) manifested as chronic cholestasis and 4 (50%) manifested as biliary cirrhosis, among whom 3 (75%) had the manifestation of portal hypertension. As for biochemical examination, 75% (6/8) had an increase in alkaline phosphatase, and 100% (8/8) had an increase in gamma-glutamyl transpeptidase. As for imaging examination, 50% (4/8) had cholecystitis, 25% (2/8) had gallstones, 25% (2/8) had bile duct dilatation, 75% (6/8) had splenomegaly, and 25% (2/8) had liver cirrhosis. As for liver biopsy, all 7 patients manifested as bile duct injury and/or reduction, and 57.1% (5/7) had absence of the bile duct. Multidrug resistance P-glycoprotein 3 (MDR3) immunohistochemical staining showed normal expression in 42.9% (3/7) of the patients and reduced expression in 57.1% (4/7) of the patients. Literature review obtained 17 articles with a description of the bile duct or MDR3 immunohistochemistry. Among the 7 patients with low phospholipid-associated cholelithiasis, 71.4% (5/7) had normal bile duct, 14.3% (1/7) had bile duct reduction, and 14.3% (1/7) had absence of the bile duct; among the 6 patients with intrahepatic cholestasis of pregnancy, 16.7% (1/6) had normal bile duct, 50% (3/6) had bile duct reduction, and 33.3% (2/6) had absence of the bile duct; among the 8 patients with PFIC3, 25% (2/8) had bile duct reduction and 75% (6/8) had absence of bile duct; among the 21 patients with PFIC3, 9.5% (2/21) had normal expression of MDR3, 23.8% (5/21) had a reduction in the expression of MDR3, and 66.7% (14/21) had absence of the expression of MDR3. Conclusion PFIC3 mainly manifests as cholestasis, cholelithiasis, and hepatic fibrosis. Pathological manifestation includes bile duct injury and bile duct reduction or absence of the bile duct in severe cases, and the degree of injury is associated with disease severity. MDR3 immunohistochemistry may show normal expression, reduced expression, or absence of expression, and diagnosis cannot be excluded in patients with normal expression. Genetic testing can be performed for diagnosis when necessary.

OBJECTIVE To establish the fingerprint of Tibetan medicine Adhatoda vasica ，and determine the contents of vasicine and vasicinone ，so as to comprehensively evaluate its quality combined with chemical pattern recognition. METHODS Using vasicine as control ，HPLC fingerprints of 11 batches of A. vasica were established with Similarity Evaluation System for Chromatographic Fingerprints of TCM （2012 edition）. The common peaks were identified and their similarities were evaluated. Cluster analysis （CA），principal component analysis （PCA）and orthogonal partial least squares-discriminant analysis （OPLS-DA） were performed by using SPSS 25 software and SIMCA 14.1 software. The variable importance in the projection （VIP）value＞1.0 was used as the standard to screen the differential components affecting the quality of A. vasica ；the contents of vasicine and vasicinone were determined by HPLC simultaneously. RESULTS A total of 23 common peaks were found ，and peak 2 was identified as vasicine ，and peak 4 was identified as vasicinone. Their similarities ranged 0.920-0.994. The results of CA showed that 11 batches of samples were clustered into 3 categories（distance was 14）：S1-S8 as one category （origin：Yunnan，Tibet），S9 as one category （origin：Yunnan），S10-S11 as one category （origin：Sichuan）；the results of P CA and OPLS-DA showed that S 9 and S10-S11 were divided into one category respectively ，and S1-S8 were further divided into 2 categories：S1，S4 as one category，S2-S3，S5-S8 as one category ；the common peaks with VIP value ＞1.0 included peak 2，peak 16，peak 21，peak 17，peak 1 and peak 13. Among 11 batches of samples ， contents of vasicine and vasicinone were 4.12-10.22 and 0.60-3.26 mg/g， respectively. CONCLUSIONS Established edu.cn HPLC fi ngerprint and content determination method are simple and accurate ，and can be used for the quality evaluation of Tibetan medicine A. vasica ，by combining with chemical pattern recognition. Vasicine and other components may be the differential components that affect the quality of the drug.

Objective:To investigate the correlation between subclinical hypothyroidism (SCH) and clinical outcomes of patients with acute ischemic stroke.Methods:From July 2014 to October 2017, patients with acute ischemic stroke admitted to Jiangsu Shengze Hospital Affiliated to Nanjing Medical University were enrolled retrospectively. Their demographic and baseline clinical and laboratory data were collected. The modified Rankin Scale was used to evaluate the clinical outcome at 3 months after the onset of symptoms. Multivariate logistic regression analysis was used to determine the independent correlation between SCH and clinical outcome of patients with acute ischemic stroke. Results:A total of 200 patients with acute ischemic stroke were enrolled, including 107 males (53.5%) and 93 females (46.5%). Their age was 69.67±11.38 years. There were 45 patients (22.5%) with SCH, 160 (80.0%) with good outcomes, and 40 (20.0%) had poor outcomes. Univariate analysis showed that there were significant differences in the baseline National Institutes of Health Stroke Scale (NIHSS) score, stroke etiology classification and the proportion of patients with SCH between the poor outcome group and the good outcome group (all P<0.05). Multivariate logistic regression analysis showed that high NIHSS score (odds ratio 2.884, 95% confidence interval 2.005-4.147; P=0.001) and SCH (odds ratio 19.527, 95% confidence interval 2.334-163.386; P=0.006) were the independent risk factors for poor outcomes. Conclusion:High NIHSS score and SCH were associated with the poor outcomes at 3 months after the onset of acute ischemic stroke.