Paraneoplastic neurologic syndromes （PNS） are immune-mediated disorders of the nervous system triggered by cross-immune response induced by tumor-associated antigens. Since high-risk paraneoplastic antibodies are highy associated with malignancies， they have an important clinical value in the early recognition， tumor screening， and prognostic assessment of PNS. The diagnostic criteria updated in 2021 further refined the classification of high-risk antibodies and clarified their value in risk assessment. This article systematically reviews the clinical spectrum， tumor associations， and immunopathogenic mechanisms of neurological disorders associated with the high-risk paraneoplastic antibodies such as anti-Hu， anti-Ri， anti-CV2， anti-Ma2， anti-amphiphysin， anti-Yo， anti-PCA2， anti-Tr， anti-SOX1， and anti-KLHL11 antibodies. Immunotherapy combined with active control of primary tumor is the main treatment strategy for such disease， but with a limited overall therapeutic effect， and early identification is of particular importance. In the era of the wide application of immune checkpoint inhibitors （ICIs）， the risk of ICIs in inducing or exacerbating should be taken seriously in clinical practice. Mechanistic research， multimodal diagnostic approaches， and individualized treatment strategies should be enhanced in the future to improve the prognosis of patients.

Background: High-mobility group box protein 1 (HMGB1) is a chromatin-binding protein involved in arthritis, ischemia, sepsis, atherosclerosis, neurodegenerative disorders, meningitis, and cancer. HMGB1 exhibits dual roles in cancer, acting as either a tumor suppressor or oncoprotein depending on context. Objective: This research aimed to elucidate HMGB1’s functional significance in cutaneous squamous cell carcinoma (cSCC). Methods: We overexpressed HMGB1 in cSCC cell lines using recombinant adenovirus and examined its effects on cell proliferation, colony formation, and cell migration. Results: Immunohistochemical analysis revealed elevated HMGB1 expression levels in cSCC tissue relative to normal epidermis. To assess the influence of HMGB1, we employed recombinant adenoviruses expressing HMGB1 to transduce SCC cell lines (SCC12 and SCC13). Enhanced HMGB1 expression significantly promoted cellular proliferation and colony formation capacity.Notably, HMGB1 overexpression elevated the levels of proliferation regulators, including P63, SOX2, CDK4 and CDK6. Furthermore, HMGB1 overexpression substantially enhanced tumor invasiveness, accompanied by upregulation of epithelial-mesenchymal transition (EMT) biomarkers. Mechanistically, overexpression of HMGB1 enhanced transforming growth factor-β signaling by increasing phosphorylation of SMAD2/3, the key mediators of EMT. Conclusion These data imply that HMGB1 acts as a tumor-promoting factor in cSCC.

The prescription of Qidong Yixin oral liquid is derived from the experience of national medical master Ren Jixue in treating viral myocarditis （VMC）. It has the functions of tonifying Qi， nourishing the heart，calming the mind， and relieving palpitations. It is used to treat VMC and angina pectoris of coronary heart disease caused by deficiency of both Qi and Yin. However，the understanding of its efficacy evidence， advantageous aspects， dosage and administration， and medication safety remains insufficient in clinical practice. Therefore，the development of the Expert Consensus on the Clinical Application of Qidong Yixin Oral Liquid （hereinafter referred to as consensus） was initiated. Consensus strictly followed the process and methods of the expert consensus on the clinical application of Chinese patent medicines of the China Association of Chinese Medicine，successively completing multiple tasks such as the consensus project initiation，determination of clinical problems，evidence search and evaluation，formation of recommendation opinions and consensus suggestions，solicitation of opinions，peer review， submission for review and release， and so on. Consensus formed a total of 10 recommendation opinions and 12 consensus suggestions，clarifying the clinical positioning，efficacy advantages，syndrome differentiation，dosage and administration，combination therapy，timing of medication，adverse reactions，contraindications， and precautions of Qidong Yixin oral liquid，indicating that it has good clinical advantages and safety in the treatment of VMC and angina pectoris of coronary heart disease，providing norms and references for physicians to safely and rationally apply Qidong Yixin oral liquid. Consensus was reviewed and approved for release by the Standardization Office of the China Association of Chinese Medicine on December 23， 2024. Standard number：GSCACM-376-2024.

Objective: To optimize the technology and process for recovering immune cells from discarded leukocyte filter through reverse flushing, and to investigate the effects of different reverse flushing solutions and physical conditions (temperature, soaking, and ultrasound) on the cell recovery rate. Additionally, to evaluate the feasibility and quality of isolating and culturing NK cells from the recovered cells. Methods: Normal saline, PBS, and PBS-EDTA were used as reverse flushing solutions to backwash the filter, and the white blood cell recovery rates were compared. The reverse flushing efficiency was optimized by adjusting the temperature of the reverse flushing solution, filter soaking treatment and ultrasonic treatment. The Ficoll separation method was employed to isolate peripheral blood mononuclear cells (PBMCs) from the elution solution and conduct in vitro expansion and culture. Lymphocyte subsets were identified and quantified using flow cytometry. Results: The physiological saline served as the backflush fluid was the most stable. The reverse temperature had a significant impact on the recovery rate of white blood cell subgroups. The recovery rates of lymphocytes and monocytes at 37℃ were significantly higher than those at 4℃ [(35.56±5.55)% vs (22.88±0.31)%, (32.42±4.82)% vs (8.00±1.6)%, t=5.581 and 5.758, respectively, both P<0.001)], and at 25℃ [(35.56±5.55)% vs (22.42±6.13)%, t=5.904, P<0.001; (32.4±4.82)% vs (21.11±1.23)%, t=2.629, P=0.030)]. The recovery rates of white blood cell subgroups after 37℃ immersion were higher than those after direct reverse flow at 37℃, but the difference was not statistically significant (P>0.05). The recovery rate of cells after ultrasonic immersion at 25℃ was further increased compared to that after immersion at 25℃, but the difference was not statistically significant (P>0.05). The purity of the NK cells obtained through sorting reached (94.2±4.5)%, and the viability was (94.8±0.9)%. After 15 days of culture, the cell count was expanded approximately 450 times, yielding more than 10 /mL highly active NK cells. Conclusion: By optimizing the backflushing process, immune cells can be efficiently recovered from discarded filters. The 37℃ backflow liquid has the best backflow effect; soaking and ultrasonic treatment can be used as auxiliary methods to improve recovery rates. The NK cells from this source have high purity, good activity, and strong expansion ability, and can be used as a reliable cell source for immunotherapy research, and in line with the circular economy concept of resource reuse.

Lung cancer constitutes the most prevalent and lethal malignant tumor in China. Approximately 85% of lung cancer diagnoses correspond to the non-small cell histological subtype [non-small cell lung cancer (NSCLC)]. Despite surgery being the mainstay for early-stage disease, postoperative recurrence remains high and adjuvant chemotherapy offers limited benefit. In recent years, targeted therapy has demonstrated substantial advantages in driver mutation-positive NSCLC. To this end, the Lung Cancer Medical Education Committee of the Chinese Medical Education Association developed guidelines based on a systematic review of evidence through November 2025, using the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) approach and a modified Delphi method. Focusing on epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK), and addressing ROS proto-oncogene 1 (ROS1), B-Raf proto-oncogene serine/threonine kinase (BRAF) V600E mutation, and mesenchymal-epithelial transition factor (MET) exon 14 (METex14) skipping, the guideline covers molecular testing, neoadjuvant/adjuvant therapy, perioperative strategies, minimal residual disease monitoring, and postoperative surveillance. It defines testing requirements, specifies stage-directed and subtype-specific treatments, and standardizes minimal residual disease monitoring. These recommendations emphasize precision and feasibility to improve survival and quality of life.

Objective:To explore the mechanism that leads to the formation of medical insurance fraud,in order to propose countermeasures and suggestions for preventing medical insurance fraud.Methods:Taking 30 provinces and cities in China as research objects,Fuzzy-Set Qualitative Comparative Analysis and Necessary Condition Analysis are applied to explore the configuration paths that lead to medical insurance fraud.Results:A single factor does not constitute a necessary condition for a high incidence of Medicare insurance fraud.There are four grouping paths that lead to a high incidence of Medicare insurance fraud,namely,the dominant factor of poor medical insurance operation status,the dual auxiliary factor of low informationization level and weak regulatory mechanism under the dominant status of poor medical insurance operation,the auxiliary pathway of low economic level under the dual dominance factors of poor medical insurance operation and low informationization level,and the three dominant factors of poor medical insurance operation as well as weak regulatory mechanism and low economic level.Conclusion:Medical insurance fraud is caused by multiple factors,therefore the following prevention strategies are proposed,focusing on rectifying and breaking through difficult problems,strengthening regulatory effectiveness through departmental linkage,enhancing regulatory accuracy through technological empowerment,and improving long-term mechanisms by addressing both symptoms and root causes.

The structure of intestinal tissue is complex. In vitro simulation of intestinal structure and function is important for studying intestinal development and diseases. Recently, organoids have been successfully constructed and they have come to play an important role in biomedical research. Organoids are miniaturized three-dimensional (3D) organs, derived from stem cells, which mimic the structure, cell types, and physiological functions of an organ, making them robust models for biomedical research. Intestinal organoids are 3D micro-organs derived from intestinal stem cells or pluripotent stem cells that can successfully simulate the complex structure and function of the intestine, thereby providing a valuable platform for intestinal development and disease research. In this article, we review the latest progress in the construction and application of intestinal organoids.
Organoids/cytology* ; Intestines/physiology* ; Humans ; Animals ; Pluripotent Stem Cells

Objective:To explore the mechanism that leads to the formation of medical insurance fraud,in order to propose countermeasures and suggestions for preventing medical insurance fraud.Methods:Taking 30 provinces and cities in China as research objects,Fuzzy-Set Qualitative Comparative Analysis and Necessary Condition Analysis are applied to explore the configuration paths that lead to medical insurance fraud.Results:A single factor does not constitute a necessary condition for a high incidence of Medicare insurance fraud.There are four grouping paths that lead to a high incidence of Medicare insurance fraud,namely,the dominant factor of poor medical insurance operation status,the dual auxiliary factor of low informationization level and weak regulatory mechanism under the dominant status of poor medical insurance operation,the auxiliary pathway of low economic level under the dual dominance factors of poor medical insurance operation and low informationization level,and the three dominant factors of poor medical insurance operation as well as weak regulatory mechanism and low economic level.Conclusion:Medical insurance fraud is caused by multiple factors,therefore the following prevention strategies are proposed,focusing on rectifying and breaking through difficult problems,strengthening regulatory effectiveness through departmental linkage,enhancing regulatory accuracy through technological empowerment,and improving long-term mechanisms by addressing both symptoms and root causes.

Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)mutations are influenced by random and uncontrollable factors,and the risk of the next widespread epidemic remains.Dual-target drugs that synergistically act on two targets exhibit strong therapeutic effects and advantages against mutations.In this study,a novel computational workflow was developed to design dual-target SARS-CoV-2 candidate inhibitors with the Envelope protein and Main protease selected as the two target proteins.The drug-like molecules of our self-constructed 3D scaffold database were used as high-throughput molecular docking probes for feature extraction of two target protein pockets.A multi-layer perceptron(MLP)was employed to embed the binding affinities into a latent space as conditional vectors to control conditional distribution.Utilizing a conditional generative neural network,cG-SchNet,with 3D Euclidean group(E3)symmetries,the conditional probability distributions of molecular 3D structures were acquired and a set of novel SARS-CoV-2 dual-target candidate inhibitors were generated.The 1D probability,2D joint probability,and 2D cumulative probability distribution results indicate that the generated sets are significantly enhanced compared to the training set in the high binding affinity area.Among the 201 generated molecules,42 molecules exhibited a sum binding affinity exceeding 17.0 kcal/mol while 9 of them having a sum binding affinity exceeding 19.0 kcal/mol,demonstrating structure diversity along with strong dual-target affinities,good absorption,distribution,metabolism,excretion,and toxicity(ADMET)properties,and ease of synthesis.Dual-target drugs are rare and difficult to find,and our"high-throughput docking-multi-conditional generation"workflow offers a wide range of options for designing or optimizing potent dual-target SARS-CoV-2 inhibitors.

Objective:To construct a risk prediction model based on ultrasound signs of prenatal fetal and accessory for adverse pregnancy outcomes of patients with placental implantation disease.Methods:This study is a prospective study.A total of 120 pregnant women who underwent hospital delivery in Tangshan maternal and child health care hospital from January 2022 to June 2023 were selected as the research objects,including 39 cases with placenta implantation and 81 cases without placenta implantation.The cases with placenta implantation were divided into adverse pregnancy group(19 cases)and good pregnancy group(20 cases)according to the different pregnancy outcome.The placental location,posterior low gyrus vocal cords of placenta,placental multiple lacunae,basal blood vessels,bladder line,and cervical sinusoids of all cases were compared.Logistic multivariate analysis was adopted to verify and construct the risk model of placenta implantation and adverse pregnancy outcomes.Results:There was significant difference in placental thickness between the cases with placenta implantation[(37.26±0.52)cm]and the cases without placenta implantation[(36.02±0.25)cm](t=14.127,P<0.05).There were significant differences between the two groups in the placenta location,posterior low gyrus vocal cords of placenta,placental multiple lacunae,basal blood vessels,bladder line and cervical sinusoids(x2=4.061,5.112,8.381,4.771,17.021,32.341,P<0.05),respectively.There was significant difference in placental thickness between the adverse pregnancy group[(36.85±0.42)cm]and the good pregnancy group[(37.45±0.24)cm](t=5.440,P<0.05).There were statistically significant differences between the two groups in the cases number of placenta location,posterior low gyrus vocal cords of placenta,placental multiple lacunae,basal blood vessels,bladder line and cervical sinusoids(x2=6.037,6.041,11.351,6.741,12.321,13.552,P<0.05),respectively.The results of multivariate analysis indicated that placental thickness,placenta location,posterior low gyrus vocal cords of placenta,placental multiple lacunae,basal blood vessels,bladder line and cervical sinusoids were the risk factors for placenta implantation of pregnant women(OR=3.300,3.374,2.995,3.384,2.843,2.878,3.053,P<0.05),respectively.Placental thickness,placenta location,posterior low gyrus vocal cords of placenta,placental multiple lacunae,basal blood vessels,bladder line and cervical sinusoids were respectively the risk factors that caused adverse pregnancy outcomes for pregnant women(OR=2.821,2.886,3.287,3.377,2.942,3.177,3.168,P<0.05).The result of receiver operating characteristic(ROC)curve indicated that the area under curve(AUC)values of the above model for placenta implantation and adverse pregnancy outcome were larger than 0.700.Conclusion:The prediction based on the model of ultrasound signs of prenatal fetal and accessory is more accurate,which can be used as important reference in clinically early diagnosis.