[摘 要] 嵌合抗原受体T细胞（CAR-T细胞）疗法在血液系统恶性肿瘤中显示出显著疗效，但传统体外制备存在流程复杂、周期长和成本高等局限。体内CAR-T细胞通过递送载体在患者体内直接重编程T细胞，有望简化制造流程并提高治疗可及性。慢病毒载体具有载荷容量较大、可稳定整合和生产体系相对成熟等优势，但其天然或假型化包膜的广谱嗜性可能导致非靶细胞转导和安全性风险。本文综述水疱性口炎病毒G蛋白（VSV-G）、Cocal病毒包膜蛋白（COCV-G）、辛德比斯病毒及麻疹病毒/尼帕病毒包膜等假型化与去受体化工程策略，讨论CD3、TCR、CD4、CD8和CD7等靶向受体的选择及CD2/CD28共刺激信号整合，并梳理相关临床前研究和早期临床转化进展。现有证据表明，靶向慢病毒可在体内生成具有抗肿瘤活性的CAR-T细胞，但仍需解决插入突变、脱靶转导、免疫原性、剂量控制和规模化生产等问题。本文旨在为下一代体内CAR-T细胞递送系统的设计与转化提供参考。

Objective:To obtain the best formulation for pysllium husk soy milk powder,the processing technology of psyllium husk soybean power by using response surface methodology.Methods:The ratio of soybean flour to black bean flour,the addition amount of psyllium husk powder and erythritol were used as the independent variables.The sensory scores obtained by senstory evalutaion was used as the dependent variable.The effects of these 3 variables on the quality of pysllium husk soybean powder was optimized by the Box-Behnken.And the optimal conditions for the processing technology were obtained.Results:The experimental results showed that the optimal ratio of soybean flour to black bean flour was 1∶1,the addition amount of psyllium husk powder was 0.1 g,the addition amount of erythritol was 2 g.Conclusion:The psyllium husk soybean powder produced under these conditions has a mellow,fresh smell and a smooth texture.

Creutzfeldt-Jakob disease(CJD)is a rapidly progressive and fatal neurodegenerative disorder caused by prions,with certain infectivity and iatrogenic transmission risks.With the rapid progress and application of new dia-gnostic biomarkers and detection methods,as well as the construction and improvement of surveillance and reporting systems,the detection of CJD in patients domestically and internationally has shown an increasing trend year by year.Due to its long incubation period and heterogeneity of early symptoms,early identification and diagnosis of the disease is difficult,increasing the risk of transmission within medical institutions.Currently,there is a lack of con-sensus on the infection prevention and control of CJD.In order to timely identify and diagnose CJD as well as effec-tively block its transmission in medical institutions,this consensus summarizes 15 clinical concerns and formulates 24 specific recommendations based on the latest domestic and international research findings and clinical evidence,as well as combines with clinical practice,aiming to standardize healthcare-associated infection prevention and control measures for CJD and reduce its transmission risk in medical institutions.

Objective:To analyze the cost and structural impact of the new technology"transhysteroscopic mechanical rotary excision of abnormal uterine tissues"on the DRG group of"surgery for intrauterine lesions"under the DRG payment method,and to provide clinical data for supporting the development of the exclusion policy for the new technology and new items.Methods:Cases in which transhysteroscopic mechanical rotary excision of abnormal uterine tissues was used in the gynecology day unit of the Peking Union Medcial College Hospital from March 2022 to November 2023,which were paid for under the DRG group of"surgery for intrauterine pathology",were retrospectively analyzed for the impact of the new technology on the cost and structure of the cases.Results:The price of"transhysteroscopic mechanical rotary excision of abnormal uterine tissues"in the Beijing Medical Service Price Item Specification is 8 000 yuan(Class C out-of-pocket expenses),which is higher than the payment standard of 6 866 yuan for the NE19 group,and the use of this new technology significantly increased the total hospitalization medical cost,the out-of-pocket ratio of the patients and the surgical cost,which led to an increase in the burden of the patients and the loss of the hospitals.Conclusion:"Transhysteroscopic mechanical rotary excision of abnormal uterine tissue"has the advantages of improving patients'prognosis and accelerating recovery,shortening operation time,avoiding intraoperative thermal injuries,and shortening the learning curve of doctors,etc.Policy makers should take into account cost control,patients'prognosis and the development of medical technology,scientifically and prudently formulate the exclusion policy of the new technology,reasonably determine the payment standard,and make good use of the exclusion policy and the payment standard.

Creutzfeldt-Jakob disease(CJD)is a rapidly progressive and fatal neurodegenerative disorder caused by prions,with certain infectivity and iatrogenic transmission risks.With the rapid progress and application of new dia-gnostic biomarkers and detection methods,as well as the construction and improvement of surveillance and reporting systems,the detection of CJD in patients domestically and internationally has shown an increasing trend year by year.Due to its long incubation period and heterogeneity of early symptoms,early identification and diagnosis of the disease is difficult,increasing the risk of transmission within medical institutions.Currently,there is a lack of con-sensus on the infection prevention and control of CJD.In order to timely identify and diagnose CJD as well as effec-tively block its transmission in medical institutions,this consensus summarizes 15 clinical concerns and formulates 24 specific recommendations based on the latest domestic and international research findings and clinical evidence,as well as combines with clinical practice,aiming to standardize healthcare-associated infection prevention and control measures for CJD and reduce its transmission risk in medical institutions.

Objective·To observe the impact of hip synovitis on the long-term outcomes of free vascularized fibular grafting(FVFG)for osteonecrosis of femoral head(ONFH).Methods·Between October 2001 and December 2013,370 patients diagnosed with ONFH(556 hips)underwent FVFG.Preoperative synovitis was assessed using magnetic resonance imaging(MRI)and quantified with the Hip Inflammation MRI Scoring System(HIMRISS).Patients were divided into no synovitis group,moderate synovitis group,and severe synovitis group.Harris hip scores and the incidence of total hip arthroplasty were collected with an average follow-up duration of 90.5 months(range:5-215 months).Hip survival failure(defined as a Harris hip score lower than 80 at the final follow-up or the occurrence of total hip arthroplasty)was calculated.Multivariable Cox regression analysis was adopted to compare the influence of different degrees of synovial inflammation on long-term prognosis.Results·The proportion of hip survival failure was 28.0％in patients without synovitis and 28.5％in those with moderate synovitis,whereas it was significantly higher(60.4％)in patients with severe synovitis.The results of multivariable Cox regression analysis showed that severe synovitis was an independent risk factor for poor prognosis(HR 2.06,95％CI 1.21-3.53)after adjusting for age,gender,education level,marital status,ONFH type,affected side of ONFH,smoking history,baseline Harris hip score and other hip MRI-based covariates(collapse,bone marrow edema,and degeneration).Conclusion·Severe synovitis in patients with ONFH significantly increases the failure rate of hip preservation after FVFG,and the severity of synovitis should be considered in surgical decision-making.

Objective:To obtain the best formulation for pysllium husk soy milk powder,the processing technology of psyllium husk soybean power by using response surface methodology.Methods:The ratio of soybean flour to black bean flour,the addition amount of psyllium husk powder and erythritol were used as the independent variables.The sensory scores obtained by senstory evalutaion was used as the dependent variable.The effects of these 3 variables on the quality of pysllium husk soybean powder was optimized by the Box-Behnken.And the optimal conditions for the processing technology were obtained.Results:The experimental results showed that the optimal ratio of soybean flour to black bean flour was 1∶1,the addition amount of psyllium husk powder was 0.1 g,the addition amount of erythritol was 2 g.Conclusion:The psyllium husk soybean powder produced under these conditions has a mellow,fresh smell and a smooth texture.

Protein tyrosine phosphatase nonreceptor type 2 (PTPN2) is a promising target for sensitizing solid tumors to immune checkpoint blockades. However, the highly polar active sites of PTPN2 hinder drug discovery efforts. Leveraging small interfering RNA (siRNA) technology, we developed a novel glutathione-responsive nano-platform HPssPT (HA/PEIss@siPtpn2) to silence PTPN2 and enhance immunotherapy efficacy in hepatocellular carcinoma (HCC). HPssPT showed potent transfection and favorable safety profiles. PTPN2 deficiency induced by HPssPT amplified the interferon γ signaling in HCC cells by increasing the phosphorylation of Janus-activated kinase 1 and signal transducer and activator of transcription 1, resulting in enhanced antigen presentation and T cell activation. The nano-platform was also able to promote the M1-like polarization of macrophages in vitro. The unique tropism of HPssPT towards tumor-associated macrophages, facilitated by hyaluronic acid coating and CD44 receptor targeting, allowed for simultaneous reprogramming of both tumor cells and tumor-associated macrophages, thereby synergistically reshaping tumor microenvironment to an immunostimulatory state. In HCC, colorectal cancer, and melanoma animal models, HPssPT monotherapy provoked robust antitumor immunity, thereby sensitizing tumors to PD-1 blockade, which provided new inspiration for siRNA-based drug discovery and tumor immunotherapy.

Objective:To analyze the cost and structural impact of the new technology"transhysteroscopic mechanical rotary excision of abnormal uterine tissues"on the DRG group of"surgery for intrauterine lesions"under the DRG payment method,and to provide clinical data for supporting the development of the exclusion policy for the new technology and new items.Methods:Cases in which transhysteroscopic mechanical rotary excision of abnormal uterine tissues was used in the gynecology day unit of the Peking Union Medcial College Hospital from March 2022 to November 2023,which were paid for under the DRG group of"surgery for intrauterine pathology",were retrospectively analyzed for the impact of the new technology on the cost and structure of the cases.Results:The price of"transhysteroscopic mechanical rotary excision of abnormal uterine tissues"in the Beijing Medical Service Price Item Specification is 8 000 yuan(Class C out-of-pocket expenses),which is higher than the payment standard of 6 866 yuan for the NE19 group,and the use of this new technology significantly increased the total hospitalization medical cost,the out-of-pocket ratio of the patients and the surgical cost,which led to an increase in the burden of the patients and the loss of the hospitals.Conclusion:"Transhysteroscopic mechanical rotary excision of abnormal uterine tissue"has the advantages of improving patients'prognosis and accelerating recovery,shortening operation time,avoiding intraoperative thermal injuries,and shortening the learning curve of doctors,etc.Policy makers should take into account cost control,patients'prognosis and the development of medical technology,scientifically and prudently formulate the exclusion policy of the new technology,reasonably determine the payment standard,and make good use of the exclusion policy and the payment standard.

Objective·To observe the impact of hip synovitis on the long-term outcomes of free vascularized fibular grafting(FVFG)for osteonecrosis of femoral head(ONFH).Methods·Between October 2001 and December 2013,370 patients diagnosed with ONFH(556 hips)underwent FVFG.Preoperative synovitis was assessed using magnetic resonance imaging(MRI)and quantified with the Hip Inflammation MRI Scoring System(HIMRISS).Patients were divided into no synovitis group,moderate synovitis group,and severe synovitis group.Harris hip scores and the incidence of total hip arthroplasty were collected with an average follow-up duration of 90.5 months(range:5-215 months).Hip survival failure(defined as a Harris hip score lower than 80 at the final follow-up or the occurrence of total hip arthroplasty)was calculated.Multivariable Cox regression analysis was adopted to compare the influence of different degrees of synovial inflammation on long-term prognosis.Results·The proportion of hip survival failure was 28.0％in patients without synovitis and 28.5％in those with moderate synovitis,whereas it was significantly higher(60.4％)in patients with severe synovitis.The results of multivariable Cox regression analysis showed that severe synovitis was an independent risk factor for poor prognosis(HR 2.06,95％CI 1.21-3.53)after adjusting for age,gender,education level,marital status,ONFH type,affected side of ONFH,smoking history,baseline Harris hip score and other hip MRI-based covariates(collapse,bone marrow edema,and degeneration).Conclusion·Severe synovitis in patients with ONFH significantly increases the failure rate of hip preservation after FVFG,and the severity of synovitis should be considered in surgical decision-making.