[摘 要] 目的：开发新型溶瘤呼肠孤病毒（Reo）递送系统，以克服中和抗体对Reo的中和作用并提升其肿瘤靶向性。方法：通过切向流过滤联合超高速离心法制备自然杀伤细胞外泌体（NKexo），叶酸（FA）修饰后采用挤压法包载Reo，构建FA-NKexo-Reo递送系统；通过透射电镜（TEM）、纳米粒径分析、蛋白质印迹（WB）法、核磁共振氢谱及流式细胞术等技术表征其理化性质；采用CCK-8、流式细胞术、Transwell实验及激光共聚焦显微镜评估FA-NKexo-Reo递送系统体外细胞毒性及细胞摄取能力；通过人卵巢癌裸鼠皮下移植瘤模型评价FA-NKexo-Reo的肿瘤靶向性、疗效及安全性。结果：FA-NKexo-Reo粒径为（94.0 ± 28.5）nm，Zeta电位为（-21.26 ± 1.57）mV，包封率达（49.7 ± 15.6）%；在中和抗体的存在下，FA-NKexo-Reo对卵巢癌细胞SKOV3和A2780仍可表现出显著的细胞毒性（P < 0.01）；荷瘤鼠活体成像显示FA-NKexo-Reo肿瘤靶向性显著优于NKexo组，肿瘤抑制率提升60%（P < 0.001）。结论：成功制备FA-NKexo-Reo递送系统，在中和抗体的存在下，FA-NKexo-Reo可保护并靶向递送Reo到高表达叶酸受体的卵巢癌细胞，从而增强Reo的抗肿瘤作用。

OBJECTIVE To investigate the effects of baicalin （BC） on insulin resistance in rats with gestational diabetes mellitus （GDM） and its underlying mechanism based on the adenosine monophosphate-activated protein kinase （AMPK）/suppressor of variegation 3-9 homolog 1 （SUV39H1）/histone H3 lysine 9 trimethylation （H3K9me3） axis. METHODS A GDM rat model was established by a combination of a high-fat diet and streptozotocin injection. The successfully modeled rats were divided into the GDM group， BC low-dose group， BC high-dose group， and high-dose of BC+AMPK inhibitor （Compound C） group， with 10 rats in each group. Another 10 pregnant rats fed a normal diet served as the control group. Rats in each group were given corresponding drugs/normal saline intragastrically and/or intraperitoneally， once daily for 2 consecutive weeks. After the last administration， the levels of fasting blood glucose （FBG）， pancreatic function indexes [fasting insulin （FINS）， homeostasis model assessment of insulin resistance （HOMA-IR）， insulin sensitivity index （ISI）]， blood lipid indexes （total cholesterol， triglyceride， low-density lipoprotein cholesterol）， liver function indexes （alanine transferase， aspartate transferase， alkaline phosphatase）， inflammatory indicators （C-reactive protein， interleukin-1β， interleukin-6）， metabolic regulatory protein [complement-C1q/tumor necrosis factor-related protein 3 （CTRP3）]， insulin sensitivity related factors [glucose transporter 4 （GLUT4）， adiponectin]， and oxidative stress indicators [superoxide dismutase （SOD）， catalase （CAT）， malondialdehyde （MDA）] were measured. Pathological changes in liver tissue were observed， and the expressions of proteins related to the AMPK/SUV39H1/H3K9me3 axis in liver tissue were detected. RESULTS Compared with the GDM group， rats in the BC low- and high-dose groups showed varying degrees of improvement in pathological changes such as disordered cell arrangement， vacuolar degeneration， lipid deposition， and inflammatory cell infiltration in liver tissue. Their FBG and FINS levels， HOMA-IR， the levels of blood lipid indexes， liver function indexes， inflammatory indicators and MDA， and the expressions of SUV39H1 and H3K9me3 were significantly decreased or down-regulated， while metabolic regulatory protein， insulin sensitivity-related factors and AMPK protein phosphorylation levels were significantly increased （ P ＜0.05）. The improvement was more significant in the BC high-dose group （ P ＜0.05）. Compound C could significantly reverse the ameliorative effects of high-dose BC on the above quantitative indicators （ P ＜0.05）. CONCLUSIONS BC can significantly reduce oxidative stress and inflammatory responses， increase serum levels of CTRP3， GLUT4 and adiponectin， thereby improving insulin resistance in GDM rats. These effects may be related to the activation of AMPK and inhibition of SUV39H1-mediated H3K9me3 modification.

ObjectiveTo analyze the epidemiological and etiological characteristics of a cluster of human metapneumovirus (HMPV) infection in a kindergarten in Gongshu District of Hangzhou City in May 2024, and to provide reference for the prevention and control of similar outbreaks. MethodsAn on-site investigation was conducted using an epidemiological case investigation form. Throat swab specimens collected from cases were screened for 13 respiratory pathogens using real-time fluorescent polymerase chain reaction (PCR). For HMPV nucleic acid positive specimens, the F gene of HMPV was used as the target gene for amplification and sequencing. The sequencing results were then compared with sequences in GenBank database to determine the virus subtypes and perform phylogenetic analyses. ResultsThe outbreak occurred in a kindergarter junior class with a total of 28 preschoolers and 3 teachers and childcare workers. A total of 11 cases (10 preschoolers and 1 teacher) were identified, including 8 male cases and 3 female cases. Clinical manifestations included fever in all 11 cases (100.00%), cough in 8 cases (72.72%), catarrhal symptoms in 4 cases (36.36%), and headache in 3 cases (27.27%). All symptoms were mild, and no severe cases were observed. A total of 11 throat swab samples were collected. Real-time fluorescent PCR test results showed that 3 samples were positive for HMPV nucleic acid, 2 samples were positive for both HMPV and Streptococcus pneumoniae, and 1 sample was positive for both HMPV and rhinovirus. The sequences of the 6 HMPV nucleic acid positive specimens were amplified and analyzed using specific primers, and all were determined to be HMPV subtype A2b. The F gene fragment sequence showed the highest similarity to PV081665.1/Brazil/2024 (99.65%), and also exhibited high similarity to PP683455.1/Indonesia/2021 (99.48%), PV016275.1/Beijing/2024 (99.31%), and PV052230.1/USA/2024 (99.13%). ConclusionThis cluster of acute respiratory tract infection was caused by HMPV subtype A2b, with co-infection of rhinovirus and Streptococcus pneumoniae. The F gene fragment sequences of the HMPV in this outbreak were highly homologous to those of the A2b strains isolated from Brazil, Beijing, Indonesia, and the the United States.

OBJECTIVE To investigate the current career development status and existing bottlenecks among graduates of clinical pharmacist training bases， and to provide evidence for optimizing the training system， enhancing trainees’ job competency， and promoting the sound development of the clinical pharmacy discipline. METHODS Graduates from a clinical pharmacist training base in a tertiary class A hospital were selected as survey subjects. A six-dimensional questionnaire was designed using “Wenjuanxing” platform， distributed and collected via a mobile APP and E-mail. The survey analyzed participants’ basic characteristics， the impact of training on their professional roles， as well as their satisfaction regarding professional sentiment， competence， career status， professional recognition， the current state of the clinical pharmacist workforce， and the teaching model of the training base. The reliability of the questionnaire responses was assessed using Cronbach’s α coefficient. RESULTS A total of 164 questionnaires were distributed， and 147 valid responses were recovered， yielding a valid response rate of 89.63%. The Cronbach’s α coefficient for the questionnaire content was 0.943. The surveyed trainees were primarily employed at general hospitals （81.63%） and tertiary class A hospitals （72.11%）， with women constituting the majority （79.59%）. Their ages were concentrated between 26 and 35 years old （63.27%）， and most of them were supervising pharmacists（59.86%）. After training， 96.60% of graduates returned to their original institutions， and the proportion working in clinical pharmacist positions increased from 52.38% to 84.35%. Trainees’ overall satisfaction rate with the training model was 84.35%. However， their satisfaction with innovation and research capacity in clinical pharmacy was only 42 .18%， the satisfaction with salary and benefits was 35.37%， and the satisfaction with both occupational recognition and rationality of staffing was less than 50%. CONCLUSIONS Clinical pharmacist training bases can effectively promote trainees’ career transition， enhance job competency， and stabilize the talent pool among trainees. Nonetheless， the profession still faces bottlenecks such as relatively weak research capacity， low compensation， insufficient professional recognition， and unreasonable staffing. These issues require a multi-pronged， collaborative approach involving the optimization of training systems， the enhancement of career support， and the improvement of industry policies.

Systemic lupus erythematosus (SLE) is a chronic autoimmune disorder affecting multiple systems, characterized by the development of harmful autoantibodies and immune complexes that lead to damage in organs and tissues. Chinese medicine (CM) plays a role in mitigating complications, enhancing treatment effectiveness, and reducing toxicity of concurrent medications, and ensuring a safe pregnancy. However, CM mainly solves the disease comprehensively through multi-target and multi-channel regulation process, therefore, its treatment mechanism is often complicated, involving many molecular links. This review introduces the research progress of pathogenesis of SLE from the aspects of genetics, epigenetics, innate immunity and acquired immunity, and then discusses the molecular mechanism and target of single Chinese herbal medicine and prescription that are commonly used and effective in clinic to treat SLE.
Lupus Erythematosus, Systemic/immunology* ; Humans ; Medicine, Chinese Traditional ; Drugs, Chinese Herbal/pharmacology* ; Animals

OBJECTIVE: To explore the effect of acupuncture therapy on dysphagia in patients with Parkinson's disease. METHODS: This randomized controlled study lasted 42 days and included 112 patients with Parkinson's disease and dysphagia. Participants were randomly assigned to the experimental and control groups (56 cases each group) using the completely randomized design, all under routine treatment. The experimental group was given acupuncture therapy. The primary outcome was Penetration-Aspiration Scale (PAS). The secondary outcomes were (1) Standardized Swallowing Assessment (SSA), and (2) nutritional status including body mass index (BMI), serum albumin, prealbumin, and hemoglobin. Adverse events were recorded as safety indicators. RESULTS: One participant quitted the study midway. There were no significant differences in baseline assessment (P>0.05). After treatment, both groups showed significant improvement in PAS, SSA and nutritional status except for BMI of the control group. There were significant differences between the two groups in the PAS for both paste and liquid, SSA (25.18±8.25 vs. 20.84±6.92), BMI (19.97±3.34 kg/m²vs. 21.26 ±2.38 kg/m²), serum albumin (35.16 ±5.29 g/L vs. 37.24 ±3.98 g/L), prealbumin (248.33 ±27.72 mg/L vs. 261.39 ±22.10 mg/L), hemoglobin (119.09±12.53 g/L vs. 126.67±13.97 g/L) (P<0.05). There were no severe adverse events during the study. CONCLUSION: The combination of routine treatment and acupuncture therapy can better improve dysphagia and nutritional status in patients with Parkinson's disease, than routine treatment solely. (registration No. CLINICALTRIAL gov NCT06199323).
Humans ; Parkinson Disease/therapy* ; Deglutition Disorders/physiopathology* ; Acupuncture Therapy/adverse effects* ; Male ; Female ; Aged ; Middle Aged ; Treatment Outcome ; Nutritional Status ; Body Mass Index

Colorectal cancer (CRC) poses a severe global health challenge with high incidence and mortality rates. USP37 has been identified as the bona fide deubiquitinase of SND1, playing a critical role in stabilizing SND1, thereby augmenting its oncogenic potential. The interaction between USP37 and SND1 was confirmed through extensive proteomics, ubiquitinomics, and interactomics, underscoring their synergistic effects on CRC proliferation and metastasis. Additionally, CDK1 has emerged as a pivotal regulator of USP37, phosphorylating it at threonine 631 rather than serine 628, enhancing its deubiquitinase activity, and consequently stabilizing SND1 to drive CRC malignancy further. Histological analyses of human CRC samples linked the upregulation of CDK1 and USP37 with increased SND1 levels and poor patient prognosis. High-throughput virtual screening and subsequent experimental validation identified Dacarbazine as a pharmacological inhibitor of USP37, and its inhibition disrupted SND1 stability, hindering CRC cell proliferation and metastasis. This study reveals a novel and promising molecular mechanism driving CRC progression through the CDK1-USP37-SND1 axis, highlighting the clinical importance of targeting this pathway to improve patient outcomes.

OBJECTIVES: To synthesize a temperature-responsive multimodal motion microrobot (MMMR) using temperature and magnetic field-assisted microfluidic droplet technology to achieve targeted drug delivery and controlled drug release. METHODS: Microfluidic droplet technology was utilized to synthesize the MMMR by mixing gelatin with magnetic microparticles. The microrobot possessed a magnetic anisotropy structure to allow its navigation and targeted drug release by controlling the temperature field and magnetic field. In the experiment, the MMMR was controlled to move in a wide range along a preset path by rotating a uniform magnetic field, and the local circular motion was driven by a planar rotating gradient magnetic field of different frequencies. The MMMR was loaded with simulated drugs, which were released in response to laser heating. RESULTS: Driven by a rotating magnetic field, the MMMR achieved linear motion following a predefined path. The planar gradient rotating magnetic field controlled circular motion of the MMMR with an adjustable radius, utilizing the centrifugal force generated by rotation. The drug-loaded MMMR successfully reached the target location under magnetic guidance, where the gelatin matrix was melted using laser heating for accurate drug release, after which the remaining magnetic particles were removed using magnetic field. CONCLUSIONS The MMMR possesses multimodal motion capabilities to enable precise navigation along a predefined path and dynamic regulation of drug release within the target area, thus having great potential for a wide range of biomedical applications.
Drug Delivery Systems/methods* ; Temperature ; Drug Liberation ; Magnetic Fields ; Robotics ; Gelatin/chemistry* ; Delayed-Action Preparations ; Microfluidics ; Motion

Cemental tear is a rare and indetectable condition unless obvious clinical signs present with the involvement of surrounding periodontal and periapical tissues. Due to its clinical manifestations similar to common dental issues, such as vertical root fracture, primary endodontic diseases, and periodontal diseases, as well as the low awareness of cemental tear for clinicians, misdiagnosis often occurs. The critical principle for cemental tear treatment is to remove torn fragments, and overlooking fragments leads to futile therapy, which could deteriorate the conditions of the affected teeth. Therefore, accurate diagnosis and subsequent appropriate interventions are vital for managing cemental tear. Novel diagnostic tools, including cone-beam computed tomography (CBCT), microscopes, and enamel matrix derivatives, have improved early detection and management, enhancing tooth retention. The implementation of standardized diagnostic criteria and treatment protocols, combined with improved clinical awareness among dental professionals, serves to mitigate risks of diagnostic errors and suboptimal therapeutic interventions. This expert consensus reviewed the epidemiology, pathogenesis, potential predisposing factors, clinical manifestations, diagnosis, differential diagnosis, treatment, and prognosis of cemental tear, aiming to provide a clinical guideline and facilitate clinicians to have a better understanding of cemental tear.
Humans ; Dental Cementum/injuries* ; Consensus ; Diagnosis, Differential ; Cone-Beam Computed Tomography ; Tooth Fractures/therapy*