Based on his extensive clinical experience and the team's mechanistic research, Professor XU Nenggui has proposed the academic concept that "the governor vessel governs the brain and treats cerebral viscus diseases", and established a novel acupuncture approach for encephalopathy treatment centered on the integrated theory of "governor vessel-brain-mind", and developed a staged acupuncture protocol of "governor vessel regulating spirit" for ischemic stroke. This article introduces the academic features of this method in treating post-stroke dysphagia from four aspects: theoretical framework, treatment principles and point selection, mechanistic research, and clinical case studies. In clinical application, the method emphasizes syndrome differentiation based on meridians, harmonization between the conception and governor vessels; precise acupoint selection to treat both form and spirit; stage-specific differentiation with targeted needling. Furthermore, Professor XU integrates basic research with clinical practice, focusing on the neurobiological mechanisms underlying the efficacy of acupuncture in treating post-stroke dysphagia.
Acupuncture Therapy/methods* ; Humans ; Deglutition Disorders/psychology* ; Stroke/complications* ; Meridians ; Acupuncture Points

BACKGROUND: Several studies have demonstrated the occurrence of secondary tumors as a rare but significant complication of chimeric antigen receptor T (CAR-T) cell therapy, underscoring the need for a detailed investigation. Given the limited variety of secondary tumor types reported to date, a comprehensive characterization of the various secondary tumors arising after CAR-T therapy is essential to understand the associated risks and to define the role of the immune microenvironment in malignant transformation. This study aims to characterize the immune microenvironment of a newly identified secondary tumor post-CAR-T therapy, to clarify its pathogenesis and potential therapeutic targets. METHODS: In this study, the bone marrow (BM) samples were collected by aspiration from the primary and secondary tumors before and after CD19 CAR-T treatment. The CD45 + BM cells were enriched with human CD45 microbeads. The CD45 + cells were then sent for 10× genomics single-cell RNA sequencing (scRNA-seq) to identify cell populations. The Cell Ranger pipeline and CellChat were used for detailed analysis. RESULTS: In this study, a rare type of secondary chronic myelomonocytic leukemia (CMML) were reported in a patient with diffuse large B-cell lymphoma (DLBCL) who had previously received CD19 CAR-T therapy. The scRNA-seq analysis revealed increased inflammatory cytokines, chemokines, and an immunosuppressive state of monocytes/macrophages, which may impair cytotoxic activity in both T and natural killer (NK) cells in secondary CMML before treatment. In contrast, their cytotoxicity was restored in secondary CMML after treatment. CONCLUSIONS This finding delineates a previously unrecognized type of secondary tumor, CMML, after CAR-T therapy and provide a framework for defining the immune microenvironment of secondary tumor occurrence after CAR-T therapy. In addition, the results provide a rationale for targeting macrophages to improve treatment strategies for CMML treatment.
Humans ; Lymphoma, Large B-Cell, Diffuse/therapy* ; Tumor Microenvironment/genetics* ; Antigens, CD19/metabolism* ; Leukemia, Myelomonocytic, Chronic/genetics* ; Immunotherapy, Adoptive/adverse effects* ; Male ; Single-Cell Analysis/methods* ; Female ; Sequence Analysis, RNA/methods* ; Receptors, Chimeric Antigen ; Middle Aged

The persistent high prevalence and poor survival outcomes of lung cancer underscore the urgent need for innovative therapeutic modalities. Here, we present a novel multifunctional delivery platform for the synergistic treatment of lung malignancies, combining in situ-triggerable photodynamic therapy (PDT) with radiotherapy. The new platform CLL was developed by loading a new reactive oxygen species (ROS)-triggerable photosensitizer, luminol-conjugated chlorin e6 (Ce6), into liposomes. CLL can be activated through the bioluminescence resonance energy transfer effect under oxidative stress, thereby producing singlet oxygen for targeted tumor treatment without external irradiation. In vitro studies showed significant cytotoxic effects of CLL in both 4T1 and A549 tumor cells. Furthermore, a PDT-radiopharmaceutical combination nanotherapy CLL-¹⁷⁷Lu was engineered by incorporating the radionuclide ¹⁷⁷Lu into CLL. CLL-¹⁷⁷Lu demonstrated synergistic antitumor effects in 4T1 and A549 tumor cells, as well as in mouse models of 4T1 breast cancer lung metastasis or A549 tumor xenografts. Mechanistically, CLL-¹⁷⁷Lu can induce singlet oxygen/ROS generation, enhance tumor cell apoptosis, and promote M1 macrophage-mediated immunotherapy. Preliminary assessments showed a favorable profile for CLL-¹⁷⁷Lu, highlighting its potential as a promising nanotherapy for cancer treatment. Additionally, CLL can serve as a versatile platform for delivering a range of therapies to achieve synergistic antitumor effects.

Accumulating evidence has demonstrated that nucleic acid-based therapies are promising for atherosclerosis. However, nearly all nucleic acid delivery systems developed for atherosclerosis necessitate injection, which results in rapid elimination and poor patient compliance. Consequently, oral delivery strategies capable of targeting atherosclerotic plaques are imperative for nucleic acid therapeutics. Herein we report the development of yeast-derived capsules (YCs) packaging an antisense oligonucleotide (AM33) targeting microRNA-33 (miR-33) for the oral treatment of atherosclerosis. YCs provide stability for AM33, preventing its premature release in the gastrointestinal tract. AM33-containing YCs, defined as YAM33, showed high transfection in macrophages, thus promoting cholesterol efflux and inhibiting foam cell formation by regulating the target genes/proteins of miR-33. Orally delivered YAM33 effectively accumulated within atherosclerotic plaques in ApoE ^-/- mice, primarily by transepithelial absorption via M cells in Peyer's patches and subsequent translocation via macrophages through the lymphatic system. Inhibition of miR-33 by oral YAM33 significantly delayed the progression of atherosclerosis. Moreover, oral treatment with YCs co-delivering AM33 and atorvastatin afforded significantly enhanced anti-atherosclerotic effects. Our findings suggest that yeast-based microcapsules represent an effective carrier for oral delivery of nucleic acids, either alone or in combination with existing drugs, offering a promising approach for precision therapy of atherosclerotic diseases.

Radon, the only naturally occurring radioactive noble gas, is among the most common radioactive nuclides to which humans are exposed. Radon can induce various biological effects in the human body and is a risk factor for lung cancer. Circular RNAs (circRNAs) are stable, tissue-specific, and abundantly expressed in body fluids. circRNAs can regulate gene expression and play an important role in the development of cancer. In this paper, we summarized the changes in the expression and function of circRNAs, highlighting the potential mechanisms of circRNAs in radon exposure-induced cancers. Our results provided theoretical support for the use of circRNAs as a biomarker of radon exposure-induced radiation damage, and offer a theoretical basis for the early diagnosis, treatment, and prevention of radon exposure-induced diseases.

Objective:To compare the etiological characteristics between influenza-like illness (ILI) cases in outpatient and emergency departments and those with severe acute respiratory infection (SARI) in Guangdong Province, hoping to provide scientific evidence for the treatment, prevention, and control of respiratory infectious diseases.Methods:Laboratory testing for multiple respiratory pathogens was conducted on 6 090 specimens collected from ILI and SARI cases in Guangdong Province from August to December 2023. Chi-square test was used to analyze the differences in positive rates. Results:The overall positive rate of respiratory pathogens was 49.5% (3 016/6 090). The positive rate was 54.5% (2 260/4 145) in ILI cases and 38.9% (756/1 945) in SARI cases. The overall positive rate was higher in ILI cases than in SARI cases across all genders and age groups, and in most cities of the province, with statistically significant differences ( P<0.05). No significant difference was found in the overall positive rate between different genders. However, the difference between different age groups was statistically significant( P<0.001), with the highest rate identified in children aged 5-14 years (57.2%, 957/1 673). The main pathogens detected in ILI cases were influenza virus, human rhinovirus/enterovirus, and Streptococcus pneumoniae, while in SARI cases they were Mycoplasma pneumoniae, human rhinovirus/enterovirus, and influenza virus. The positive rates of adenovirus, human parainfluenza virus, SARS-CoV-2, human coronavirus, influenza virus, and Streptococcus pneumoniae were significantly higher in ILI cases than in SARI cases, while the positive rate of Mycoplasma pneumoniae was significantly higher in SARI cases ( P<0.05). Moreover, ILI cases were characterized by a higher risk of coinfection compared with SARI cases, especially in males or those aged 25-59 years. Conclusions:There are differences in the detection rates and spectrum of respiratory pathogens between ILI and SARI cases in Guangdong Province. Case features should be considered when developing strategies for preventing and treating respiratory infections.

Objective:To investigate the effect of circular RNAs (circRNAs) expressions in peripheral blood of residents around radon hot springs.Methods:Totally 51 residents around radon hot springs were selected as the radon hot sping group, and another 51 residents around non-radon hot springs were selected as the control group. Questionnaires were used to collect demographic information and the radon exposure levels in the two groups. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to detect the relative expressions of selected circRNA candidates in peripheral blood of the two groups. Mann-Whitney U test was used to compare the differences in the relative expressions of the circRNAs between the two groups. Results:The cumulative doses of radon exposure per capita for residents around radon hot springs was (111.47±99.03) mSv, with dose range 3.32-458.68 mSv. The difference in the relative expressions of hsa_circ_0040573 between the two groups was statistically significant ( Z=-2.88, P<0.05). The expression of hsa_circ_0040573 was suppressed by radon exposure ( t=-2.52, P<0.05) with a dose-dependent manner ( H=12.21, P<0.05). Conclusion:Hsa_circ_0040573 has a potential to serve as a radiological response biomarker for radon exposure, contributing to early diagnosis and monitoring of health risks associated with radon exposure.

Objective:To investigate the number of medical institutions and staff involved in 131I diagnosis and therapy in China, and to ascertain the level of 131I activity incorporated in thyroid of medical staff performing the 131I treatment. Methods:Questionnaires were used to investigate the basic information on nuclear medicine practices in all the non-military hospitals in China. Portable gamma spectrometers were used to determine and analyze the 131I activity in thyroid of the medical staff in some radioiodine treatment workplaces. The result were reported through National Radiological Health Information Platform. Results:Until December 2022, there had been 959 hospitals performing clinical nuclear medicine practices in China, with a total of 10 820 medical staff. In China, there have been 623 hospitals performing 131I therapeutical procedures, accounting for 65.0% of all nuclear medicine hospitals, and 333 hospitals performing 131I treatment of thyroid cancer, accounting for 34.7%. The hospitals equipped with automated radiopharmaceutical dispenser accounted for 61.3% of the 623 hospitals. A total of 2 210 nuclear medicine staff were monitored for internal exposure in 20 provinces in 2022, with 249 (11.3%) having activities above 100 Bq and the maximum value of 2.9 × 10 4 Bq. A total of 426 nuclear medicine staff in four provinces were detected using HPGe detectors, with 101 (23.7%) detected to have 131I in their thyroid glands. A total of 1 748 in 17 provinces were detected using NaI or LaBr detectors, with 379 (21.2%) detected to have 131I in their thyroid glands. The detection rate of 131I in the staff was found to increase with the increased amount of 131I purchased by hospitals. The detection rate of 131I in the hosptitals having purchased the amount of 131I≥3.70 × 10 6 MBq in 2021 was 32.1%. This value was notably higher than in the other three groups whose purchased amount <3.70 × 10 6 MBq, with a statistically significant difference( χ2=15.46, P < 0.001). Conclusions:There were great differences in the number of both hospitals and staff performing 131I treatment between different provinces in China. About one fifth of the staff in the 131I treatment workplaces could be detected to have incorporated 131I in their thyroid glands.

Objective To prepare neutrophil-responsive luminescent nanomicelles based on self-luminating compound,luminol,and investigate their imaging capability for a mouse burn model at early stage of inflammation.Methods Hexachlorotripolyphosphazene(HCCP)was utilized as the skeleton material to synthesize amphiphilic LHP luminescence materials through chemical synthesis of luminol and polyethylene glycol(PEG).The chemical structure of LHP was characterized using infrared spectrum and nuclear magnetic hydrogen spectrum.Nanomicelle LHP NM was formed by self-assembly of LHP in deionized water,and then its particle size and potential were measured.Transmission electron microscopy(TEM)was applied to observe the morphology of nanomicelles.Optical fiber spectrometer,weak luminescence measuring instrument,and small animal living imager were employed to evaluate the spectroscopic properties,chemiluminescence rules,and in vitro luminescence imaging ability of the nanomicelles.After that,female Balb/c mice were subjected to scalding with hot water at temperatures of 70℃,80℃,and 90℃,respectively to establish a mouse burn model ranging from degree Ⅰ to degree Ⅱ burns.The depth of skin scalds in the model mice was determined through HE staining,while the expression levels of TNF-α,IL-1β,IL-6 and myeloperoxidase(MPO)in the scalded skin tissues were assessed with fluorescence quantitative qPCR.The changes in reactive oxygen species(ROS)levels over time and burn depth in the skin tissues were determined with ROS detection kit.Additionally,the neutrophils within the skin tissues of model mice were labeled with FITC-Ly6G antibody to count the neutrophil number.Finally,a small animal imaging system was utilized to examine the imaging capability of nanomicelle LHP NM in a mouse burn model to analyze the correlation between luminous intensity and number of recruited neutrophil in order to evaluate the effectiveness of luminous nanomicelles for monitoring early inflammatory response and diagnosing burn depth in a mouse burn model.Results Nuclear magnetic resonance(NMR)spectroscopy confirmed the bonding of approximately 5 luminol units and a polyethylene glycol(PEG)chain to 1 HCCP molecule.TEM and particle size determination results demonstrated that the prepared nanomicelles were spherical,hollow structures in a diameter of around 120 nm.In vitro luminescence experiments revealed that the nanomicelles exhibited high brightness and sustained chemiluminescence under varying concentrations of ROS and MPO levels,with luminescence intensity dependent on both ROS level and nanomicelle concentration.The in vitro cellular experiments demonstrated that the nanomicelles exhibited neutrophil-responsive imaging capability.The luminescence intensity was positively correlated with both the number of neutrophils and the dose of LHP NM,with a linear correlation coefficient(r)of 0.98 and 0.99,respectively.In vivo animal study revealed a significant increase(P<0.05)in the count of neutrophils and ROS level in the skin tissue of burned and scalded mice.Notably,at the time point of 24 h,compared to the 80℃and 70℃treatment groups,the number of recruited neutrophils was increased by 86.4％,and the luminescent imaging intensity rose by 71.5％.These findings indicated that the severity of burns was correlated with the extent of neutrophil recruitment in the injured area,and LHP NM could effectively achieve neutrophil-responsive imaging in model mice.The changes in imaging intensity were closely associated with the number of neutrophils and the level of ROS in the injured skin tissue.Conclusion The neutrophil-responsive luminescent nanomicelle LHP NM is successful prepared,and the nanomicelles enable responsive imaging of skin damage in mouse burn model.The luminescence intensity accurately reflects the neutrophil infiltration and ROS level,allowing for real-time monitoring of early inflammatory responses in mouse burn model.Additionally,this study provides methods and strategies for diagnosing burn depth.

This study aims to determine the therapeutic effect and then elucidate the molecular mechanism of Dietary Yangrong Decoction(DYRT)on blood deficiency syndrome based on net-work pharmacology and study its active compounds.The molecular mechanism of DYRT in the treatment of blood deficiency syndrome was predicted by network pharmacology.The blood defi-ciency of rats was established using cyclophosphamide and acetophenohydrazine jointly,which was divided into a blank control group,a model group,a Men's Yangrong Decoction group(MYRT)(positive control group),a medicinal group and food-based Yangrong Decoction group.The active components were analyzed by liquid chromatography-mass spectrometry(HPLC-MS),the periph-eral hemogram was detected by an automatic biochemical analyzer,the levels of hematopoietic regulatory factors in serum were determined by ELISA,and the relative expression of EPO in kid-ney and PI3K,AKT,GM-CSF in bone marrow were measured by RT-PCR.The results showed that DYRT had 57 active ingredients and 128 potential targets for the treatment of spleen deficien-cy syndrome.1 835 items were obtained by GO enrichment analysis,and 20 pathways were ob-tained by KEGG enrichment analysis;DYRT and MYRT were identified by HPLC-MS to contain 12 same blood active compounds.Animal experiments showed that,compared with the model group,the number of red blood cells,the number of platelets and the content of hemoglobin in the DYRT group were significantly increased,and the number of white blood cells was significantly decreased(P＜0.05).The contents of EPO,IL-3,IL-6 and GM-CSF in serum were significantly in-creased,and the content of TNF-α was significantly decreased(P＜0.05).The relative expression levels of EPO in kidney and PI3K,AKT and GM-CSF mRNA in bone marrow were significantly increased(P＜0.05).Compared with the MYRT group,the number of white blood cells in the DYRT group was significantly reduced,the content of GM-CSF in serum was significantly in-creased,and the content of EPO and GM-CSF mRNA was significantly increased(P＜0.05).In conclusion,DYRT contains the same active compounds as MYRT,which can regulate hematopoi-etic factors,thereby activating the PI3K/AKT pathway to restore hematopoietic function and im-prove the blood deficiency state of the body.