Tuberous sclerosis complex (TSC) is an autosomal dominant genetic disorder primarily caused by pathogenic variants in the TSC1 or TSC2 genes. It is characterized by multisystem hamartomatous lesions and neuropsychiatric manifestations. Here we report a young male patient with TSC involving multiple organs, caused by a heterozygous frameshift mutation in TSC2 (c.2071delC, p.Arg691Alafs^*7). The patient initially presented with classic facial angiofibromas and hypomelanotic macules, and subsequently developed psychiatric and behavioral disturbances with auditory hallucinations. Neuroimaging revealed an intracranial mass lesion, which was confirmed as a subependymal giant cell astrocytoma on postoperative histopathology following surgery performed at an outside institution. After admission, the patient underwent a comprehensive diagnostic workup, and multidisciplinary treatment evaluation revealed extensive multisystem involve-ment, including the nervous system, skin, kidneys, lungs, heart, eyes, pancreas, liver and bones. Combined with relevant literature, this article discusses the molecular mechanisms, clinical phenotypes, and comprehensive management of TSC, in order to provide a reference for the standardized and individualized management of this disease.

Background/Aims: Lenvatinib resistance remains a critical barrier in advanced hepatocellular carcinoma (HCC) therapy. However, the underlying mechanisms and strategies for reversing resistance remain incompletely understood. Methods: Integrated transcriptomics of lenvatinib-resistant patient tumors and an acquired-resistance murine model identified a novel macrophage subpopulation. Functional validation employed CRISPR-SAM screening, conditioned medium (CM) assays, subcutaneous/orthotopic xenografts, patient-derived organoids (PDOs), and patient-derived xenografts (PDXs). Mechanistic studies included ChIP-qPCR, co-immunoprecipitation, and pharmacologic targeting. Clinical relevance was assessed in a retrospective cohort. Results: Resistant HCC exhibited significant enrichment of a COLEC12high TAM subset , which correlated with poor survival and treatment response. These TAMs secreted neuregulin-1 (NRG1) , activating HER2/HER3-AKT signaling in tumor cells to drive cancer stemness and lenvatinib resistance. Mechanistically, in TAMs COLEC12 sequestered STAT1 in the cytoplasm, preventing its phosphorylation, and thereby derepressing STAT3-mediated NRG1 transcription. Depletion of NRG1 reversed the stemness phenotypes and resensitized tumors to lenvatinib both in vitro and in vivo. Clinically, high NRG1 expression predicted an inferior lenvatinib response and shorter survival. Crucially, the bispecific anti-HER2/HER3 antibody zenocutuzumab restored lenvatinib efficacy in PDOs, PDXs, and murine models. Conclusions Our work establishes the COLEC12high TAM/NRG1 axis as a master regulator of therapeutic resistance and identifies NRG1 as a predictive biomarker, providing a clinically actionable strategy to overcome lenvatinib resistance in HCC.

Objective To systematically evaluate the therapeutic effects of video-assisted thoracoscopic surgery (VATS) and robot-assisted thoracic surgery (RATS) in treating mediastinal tumors. Methods A computer search was conducted on PubMed, Embase, Cochrane Library, Web of Science, Wanfang, CNKI, CBM, VIP databases for literature comparing the clinical efficacy of VATS and RATS in treating mediastinal tumors, with the search time from inception to March 31, 2024. The Newcastle-Ottawa Scale (NOS) was used to evaluate the quality of the included cohort studies, and Review Manager 5.4 software was used to perform a meta-analysis. Results A total of 32 articles were included, with 7868 patients. The NOS scores of the included cohort studies were all≥7 points. Meta-analysis results showed that compared with the VATS group, the RATS group had less intraoperative blood loss [MD=−16.71, 95%CI (−23.88, −9.54), P<0.001], lower conversion rate to open thoracotomy [OR=0.41, 95%CI (0.26, 0.67), P=0.003], lower overall postoperative complication rate [OR=0.66, 95%CI (0.48, 0.92), P=0.01], shorter postoperative drainage time [MD=−0.64, 95%CI (−0.92, −0.36), P<0.001], and shorter postoperative hospital stay [MD=−1.03, 95%CI (−1.28, −0.78), P<0.001]. There was no statistical difference between the two groups in terms of tumor size [MD=−0.06, 95%CI (−0.31, 0.19), P=0.64] or operation time [MD=5.52, 95%CI (−2.35, 13.40), P=0.17]. The RATS group had higher hospitalization costs than the VATS group [MD=1.69, 95%CI (1.26, 2.13), P<0.001]. Conclusion In mediastinal tumors resection, RATS is superior to VATS in terms of intraoperative blood loss, conversion rate to open thoracotomy, overall postoperative complication rate, postoperative drainage time, and postoperative hospital stay, but it increases hospitalization costs.

To investigate the epidemiological characteristics of venous thromboembolism (VTE) among inpatients at the People's Hospital of Xizang Autonomous Region, and to provide data support for the establishment of a standardized risk screening and pharmaceutical care system in the plateau chronic disease pharmaceutical clinic.

OBJECTIVE To evaluate the clinical efficacy and safety of eravacycline in intensive care unit （ICU） patients with carbapenem-resistant Acinetobacter baumannii （CRAB） and/or carbapenem-resistant Klebsiella pneumoniae （CRKP） pneumonia.METHODS Clinical data of patients with CRAB and/or CRKP pneumonia who were admitted to the ICU of Peking Union Medical College Hospital， Chinese Academy of Medical Sciences， and received eravacycline treatment from July 2023 to November 2024 were collected. The 28-day all-cause mortality rate， clinical failure rate， 28-day ICU-free days among surviving patients， 28-day mechanical ventilation-free days among surviving patients， microbiological clearance， and adverse reactions were recorded.RESULTS A total of 37 patients were included. Among the 37 patients， 11 （29.73%） experienced clinical failure， and the 28-day all-cause mortality rate was 18.92% （7/37）. The 28-day ICU-free days among surviving patients were （14.60±10.61） days， and the 28-day mechanical ventilation-free days among surviving patients were （24.55±4.29） days. Microbiological clearance was achieved in 12 patients （32.43%）， and the mean time to conversion was （10.58±12.05） days. Adverse reactions occurred in 5 patients （13.51%）， including 2 cases of elevated liver enzymes， 2 cases of coagulopathy， and 1 case of drug hypersensitivity syndrome.CONCLUSIONS Eravacycline can effectively control systemic bacterial infection and inflammatory response in ICU patients with pneumonia caused by CRAB and/or CRKP. However， patients with underlying liver disease or receiving multiple antibacterial agents should be alert to elevated liver enzymes， coagulation abnormalities， and the rare drug hypersensitivity syndrome.

In classical medical literature， the concept of "toxin" in traditional Chinese medicine （TCM） encompasses medicinal properties， etiology and pathogenesis， syndromes， and treatment. Its connotations extend beyond the intrinsic potency and potential toxicity of medicinal substances to include pathological states characterized by the accumulation， latent persistence， transmission and transformation of pathogenic toxins， as well as the turbid stagnation. The concept also involves the nomenclature of toxin-related disorders and therapeutic strategies for the application and elimination of toxins. Previous studies have largely focused on individual medical classics， specific diseases， or drug toxicity， while different conceptual levels of toxin have often been conflated. After briefly tracing broader semantics of toxin， this paper adopts medical properties， etiology and pathogenesis， syndromes and treatment as the analytical framework to examine the historical evolution of its medical connotations across different historical periods， aiming to clarify the conceptual hierarchy of toxin in TCM and elucidate its developmental trajectory. The basic meanings of toxin took shape in the pre-Qin and Qin-Han dynasties， encompassing medicinal efficacy and risks， pathogenic qi leading to damage， disease and syndrome nomenclature， and the principles of using toxic substances to treat diseases. The understanding of accumulation， latent persistence， and transmission of toxin pathogen， as well as residual toxin was further enriched in the Jin-Sui-Tang dynasties. The materia medica standardization and syndrome-based treatment of toxin were witnessed in the Song-Jin-Yuan dynaties， while further elaboration of the toxin concept in warm epidemic， warm disease， and surgery were promoted during the Ming-Qing dyanties. In the modern and contemporary periods， more complex pathogenic concepts emerged， including collateral damage by toxin， toxin bi （痹）， and turbid toxin. These historical developments provide important documentary evidence for the standardization of related terminology， syndrome research， and the safety evaluation of medicinal applications.

As people’s attention to health continues to increase, the market demand for traditional Chinese medicine (TCM) is growing steadily. The quality and safety of Chinese medicinal materials have attracted unprecedented social attention. In particular, the issue of exogenous harmful residue pollution in TCM has become a hot topic of concern for both regulatory authorities and society. The Chinese Pharmacopoeia 2025 Edition further refines the detection methods and limit standards for exogenous harmful residues in TCM. This not only reflects China’s high-level emphasis on the quality and safety of TCM but also demonstrates the continuous progress made by China in the field of TCM safety supervision. Basis on this study, by systematically reviewing the development history of the detection standards for exogenous harmful residues in TCM and analyzing the revisions and updates of these detection standards in the Chinese Pharmacopoeia 2025 Edition, deeply explores the key points of the changes in the monitoring standards for exogenous harmful residues in TCM in the Chinese Pharmacopoeia 2025 Edition. Moreover, it interprets the future development directions of the detection of exogenous residues in TCM, aiming to provide a reference for the formulation of TCM safety supervision policies.

Objective To evaluate the safety and feasibility of remote robot-assisted thoracoscopic surgery utilizing 5G technology. Methods Clinical data from five patients who underwent 5G remote robot-assisted thoracoscopic surgery at the Thoracic Surgery Center of Gansu Provincial People's Hospital from May to October 2024 were retrospectively analyzed. Results Finally, five patients were included. There were 2 males and 3 females at median age of 50 (42-63) years. All five surgeries (including 1 patient of lobectomy, 3 patients of partial lung resection and 1 patient of mediastinal lesion resection) were successfully completed without conversion to thoracotomy, complications, or mortality. The median intraoperative signal delay across the patients was 39 (37-42) ms. The median psychological load score for the surgeons was 9 (3-13). The median operation time was 100 (80-122) minutes with a median intraoperative blood loss of 100 (30-200) mL. Catheter drainage lasted a median of 4 (3-5) days, and the median drainage volumes on the first, second, and third postoperative day were 200 (100-300) mL, 150 (60-220) mL, and 80 (30-180) mL, respectively. The median postoperative hospital stay was 4 (3-7) days, and the median pain scores on the third postoperative day were 3 (1-4), 3 (0-3), and 1 (0-3), respectively. Conclusion 5G remote robot-assisted thoracoscopic surgery is safe and effective, with good surgical experience, smooth operation and small intraoperative delay.

OBJECTIVE To establish a management index system for off-label drug use in medical institutions， offering a reference for the improvement of the management of off-label drug use in medical institutions from Xizang region. METHODS The framework of the management index of off-label drug use was initially developed based on regulations， literature retrieval and group discussion. Then，two rounds of Delphi consultation were conducted via the “Wenjuanxing” mobile mini-program involving 10 in-hospital experts from the fields of medicine， pharmacy， and hospital management. The consultation results were then sorted， revised and statistically analyzed， the final index system was established. RESULTS The questionnaire recovery rates of the two rounds of expert consultation were both 100%. The judgment coefficients were both 0.93， the familiarity degrees were both 0.74， and the authority coefficients were 0.84 in both rounds. Kendall’s coordination coefficients were 0.278 and 0.308， respectively （P＜ 0.001）， and the full score rates in both rounds were no less than 20%. The final management index system for off-label drug use in the hospital was established， including 3 first-level indicators（off-label drug use graded management regulations， off-label drug use supervision model， off-label drug use management level quantitative assessment system）， 14 second-level indicators （such as management level classification and key points of informed consent， etc.）， and 52 third-level indicators（such as general use level， restricted-use level， and special-use level， etc.）. CONCLUSIONS The management indicators for off-label drug use developed in this study， which are established based on Delphi method， are aligned with practical needs of hospital operations and meet the standards of expert enthusiasm， authority， and consistency.

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