[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。

Attention deficit hyperactivity disorder （ADHD） is often accompanied by tic disorder. The core pathogenesis is considered to be ministerial fire scorching yin and internal stirring of deficient wind， which leads to disharmony between the body and spirit， resulting in clinical manifestations. The treatment principles emphasize nourishing yin fluids， calming ministerial fire， and extinguishing endogenous wind （内风）. The method of nourishing yin fluids is applied throughout the entire treatment process， commonly using ingredients such as Shudihuang （Rehmanniae Radix Praeparata）， Shanzhuyu （Corni Fructus）， Gouqizi （Lycii Fructus）， Wuweizi （Schisandrae Chinensis Fructus）， and Tusizi （Cuscutae Semen）. These are combined with approaches to harmonize the zang-fu organs， primarily including extinguishing liver wind， clearing heart fire， nourishing kidney water， and strengthening spleen earth， thereby stabilizing ministerial fire and extinguishing endogenous wind. Additionally， emotional regulation and smoothing emotional constraint are essential to improve clinical symptoms in children with ADHD comorbid with tic disorder.

This paper summarizes Professor WANG Xixing's clinical experience in treating immune checkpoint inhibitor-related pneumonitis （CIP） based on the theory of "cough attributed to the five zang （脏） organs". Cough is a common predominant symptom of CIP. According to the theory of "cough attributed to the five zang organs"， drug toxicity triggers cancer toxin， leading to disharmony among the five zang organs， and then lung failing to diffuse and govern descent as the core pathogenesis. Therefore， treatment should focus on harmonizing the five zang organs to restore the normal function of lung qi to diffuse and govern descent. In clinical practice， CIP can be classified into four syndrome patterns， including lung yin depletion， deficiency of both the lung and the spleen with phlegm-dampness， liver fire harassing the lung， and lung-kidney yin deficiency. Correspondingly， Chaimai Jinluo Runfei Decoction （柴麦金络润肺汤） is used to nourish yin and moisten the lung； Qigui Peitu Huayin Decoction （芪桂培土化饮汤） is used to fortify the spleen and tonify the lung， resolve dampness and dispel phlegm； Chaidan Shuyu Runjin Decoction （柴丹疏郁润金汤） is used to drain liver and clear the lung； and Dimai Jinshui Xiangsheng Decoction （地脉金水相生汤） is used to nourish the kidney and moisten the lung.

Objective To investigate the diagnosis and treatment of 2 cases with spontaneous renal vascular rupture, and discuss the possible causes and treatment methods of this disease. Methods The clinical data and treatment methods of the 2 patients with spontaneous renal vascular rupture treated with renal artery embolization in Universal Global Xi'an Beihuan Hospital were analyzed. Relevant literature was reviewed to summarize the possible causes of this condition. Results The patients had no obvious history of trauma and no obvious abnormal coagulation function, and sought treatment due to sudden lumbar and abdominal pain. Laboratory tests revealed significantly decreased hemoglobin level, and elevated blood glucose (27.8, 27.6mmol/L). Abdominal computed tomography (CT) indicated perirenal hematoma and active bleeding. The bleeding arteries were located at the terminal branches of the anterior renal artery. Precise embolization was performed using CT angiography and selective renal artery angiography plus embolization, achieving an immediate hemostasis success rate of 100%. Postoperative hemoglobin level stabilized, and follow-up CT scans showed significant absorption of the perirenal hematoma without significant deterioration of renal function. Based on literature review and case analysis, the possible cause of spontaneous renal vascular rupture in these two patients was renal vascular sclerosis due to long-term diabetes. Other common etiologies of this condition included renal tumor, vascular malformation, and hypertension. Conclusion Spontaneous renal vascular rupture is rare. Renal artery embolization, as aminimally invasive treatment, can effectively control bleeding and protect renal function. The specific pathogenesis of this condition still requires further investigation. Long-term diabetes mellitus with poor blood glucose control may be associated factors, but more evidence is needed.

It is proposed that cold qi-induced accumulation encapsulates the core pathogenesis of the inflammation-cancer transformation in inflammatory bowel disease （IBD）. Cold pathogens may serve as the initiating factor. When first invading the intestines， cold pathogens obstruct the flow of qi； over time， the lingering cold impairs the middle jiao （焦）， eventually leading to the accumulation of cold-phlegm and blood stasis. Based on the progressive nature of this transformation， the process can be divided into three stages， active stage， remission stage， and carcinogenic stage. In the active stage， the main pathogenesis involves stagnation of cold qi and accumulation of damp-heat in the intestines； in the remission stage， cold qi impairs the spleen， disrupting its transport and transformation functions； and in the carcinogenic stage， the mechanisms include cold-induced accumulation， phlegm accumulation from cold， and stagnation of cold and blood stasis. Accordingly， the treatment strategies are proposed.In the active stage， regulating qi， relieving stagnation， and harmonizing cold and heat； in the remission stage， warming yang， dispersing cold， tonifying qi， and strengthening the spleen； and in the carcinogenic stage， promoting qi circulation， dispersing cold， resolving phlegm， activating yang， and eliminating stasis to remove accumulation. These approaches aim to interrupt the transformation of IBD into colorectal cancer.

Mild cognitive impairment due to Alzheimer′s disease is an inevitable pathological stage in the early development of Alzheimer′s disease, which can be classified as "microlumps in the brain collaterals" in traditional Chinese medicine. Based on the theory of latent toxin blocking collaterals, this article discusses the etiology and pathogenesis, clinical sequelae, and traditional Chinese medicine intervention strategies for mild cognitive impairment due to Alzheimer′s disease. The onset of mild cognitive impairment due to Alzheimer′s disease is very similar to the latent pathogen theory, which states that "the latent pathogen is latent and then develops, the poison is deep and difficult to cure, and the development can be recognized but the latent pathogen cannot be detected." Combining clinical experience, our team believes that the basic nature of the disease is a slight deficiency and a slight excess of symptoms. A slight deficiency of the five zang viscera and six fu viscera as root and a latent toxin colling collaterals of qi, fire, phlegm, and blood stasis as manifestaion. These usually start from the qi depression and develop into phlegm coagulation and blood stasis, then end up in latent toxin and gradually become the healthy qi deficiency. Therefore, the deficiency of vital qi and incubation of evil, latent toxin blocking collaterals the pathogenesis of early intervention of this disease should be carried out, upholding the idea that "the upper workman treats the disease before it is diagnosed." The principle of strengthening vital qi to eliminate pathogenic factors, slowing down and promoting pathogenic factors elimination, establishing the method of supporting correctness and wisdom, simultaneously detoxifying and clearing the blood stasis, pattern differentiation as the main and the disease differentiation as the first, combining the disease and pattern, and adjusting the macroscopic and microscopic, focusing simultaneously on eliminating and replenishing, dispel phlegm and remove blood stasis, achieve a strong vital qi and the elimination of evil, and enhance intelligence, delay or even block the progression of mild cognitive impairment due to Alzheimer′s disease, improve patients′ quality of life, and provide a theoretical basis for the early clinical prevention and treatment of Alzheimer′s disease.

Objective To track and evaluate the implementation and application of the occupational health standard Radiation shielding requirements for radiotherapy room—Part 4: Radiotherapy room of ²⁵²Cf neutron afterloading (GBZ/T 201.4-2015) by radiation health technical service agencies, medical institutions, health supervision agencies, and radiotherapy facility design units, and to provide a scientific basis for the further revision and implementation of this standard. Methods Following the Guideline for health standards tracking evaluation (WS/T 536-2017) and the project implementation plan, relevant practitioners were randomly selected for a questionnaire survey. The survey primarily focused on their awareness, standard training, application, and revision suggestions of GBZ/T 201.4-2015. The results were summarized and analyzed. Results A total of 168 evaluation questionnaires were collected from relevant practitioners in 28 provinces. Only 31.6% of the respondents reported being “well familiar” or “ familiar” with the standard, 27.4% of the respondents believed that the standard was widely used, and 45.2% of the respondents believed that the standard could meet the needs of their work. Only 14.9% of the respondents had received relevant training on the standard, more than half of the respondents had not applied the standard within the past 10 years, and 45.2% of the respondents believed that the standard "needs to be revised". Conclusion Due to the small number of californium-252 neutron afterloading radiotherapy devices in operation on the market, the overall awareness of the standard is low, suggesting that relevant authorities need to strengthen training and publicity of the standard, and that certain sections of the standard need to be revised or merged.

Objective To guide occupational health inspectors in accurately identifying the key points of law enforcement and case management during the supervision of occupational health technical service institutions, standardize the collection of evidence for illegal activities and the application of legal provisions, ensure the proper execution of administrative penalties, and provide insights for handling cases related to the supervision and law enforcement of occupational health technical services. Methods This study analyzed the key points of evidence collection using an example case involving an entity that engaged in occupational health test and evaluation technical services without obtaining the required qualifications for occupational health technical service institutions. Results The key points of evidence collection primarily included: evidence proving the qualification of the penalized subject, evidence proving jurisdictional authority, evidence proving the conduct of occupational health technical services, evidence proving the absence of an Occupational Health Technical Service Institution Qualification Certificate, evidence proving illegal gains, evidence proving the circumstances of the violation, and other evidence proving the legality of administrative procedures. Conclusion In the implementation of administrative penalties by occupational health supervisors, standardized investigation and evidence collection constitute a critical component of law enforcement and case handling. Sufficient evidence collection and accurate application of the law are indispensable for safeguarding public health and societal interests against infringement.

Objective To summarize the best evidence concerning the prevention and management of indwelling line complications in patients with hepatocellular carcinoma(HCC)receiving hepatic artery infusion chemotherapy(HAIC),and to standardize the key contents of clinical observation of complications during HAIC treatment.Methods By using the"6S"pyramid model system,the relevant literature was searched in the order from high to low.Two professionals evaluated the quality of the literature,summarized the evidence and conducted the analysis and summarization.Results Ten literature articles were finally enrolled in this study,including one article of guideline,one article of systematic review,five articles of expert consensus,one article of meta-analysis,and two articles of randomized controlled trials.Six complications(catheter displacement or falling off,catheter obstruction,unplanned extubation,arterial spasm or occlusion,infection,puncture site bleeding/local hematoma)and 22 pieces of best evidence for prevention management were summarized.Conclusion This study systematically summarizes 6 complications and their prevention and treatment in patients with HCC receiving HAIC,providing a reliable basis for clinical practice.

Objective To investigate the value of early maternal serological indicators in predic-ting the delivery of full-term small-for-gestational-age(SGA)infants.Methods The clinical data of pregnant women who delivered at Beijing Tongzhou District Maternal and Child Health Hospital from August 2023 to August 2024 were analyzed.A total of 180 pregnant women who delivered full-term SGA infants were included in case group,and 180 pregnant women who delivered full-term appropri-ate-for-gestational-age(AGA)infants during the same period were included in control group.The levels of serum pregnancy-associated plasma protein A(PAPP-A),placenta growth factor(PLGF),and soluble fms-like tyrosine kinase-1(sFlt-1)in the first trimester(11 to 13 weeks+6 days of ges-tation)of the two groups were compared.Receiver operating characteristic(ROC)curves were used to analyze the predictive value of early maternal serological indicators for the delivery of full-term SGA infants.Results The levels of serum PAPP-A and PLGF in the first trimester of the case group were lower than those in the control group,while the level of sFlt-1 was higher(P＜0.05).The area un-der the ROC curve(AUC)for the combined detection of serum PAPP-A,PLGF,and sFlt-1 levels in the first trimester in predicting the delivery of full-term SGA infants was 0.823,which was higher than the AUCs for detection of each indicator(0.738,0.720,0.724)(P＜0.05).Conclusion The detection of early maternal PAPP-A,PLGF,and sFlt-1 levels can reflect the fetal growth status in utero.The combined detection of these three indicators has a higher predictive value for the delivery of full-term SGA infants by pregnant women,which is helpful for clinicians to take intervention measures in advance.