Objective To reveal the scientific output and trends in pulmonary nodules/early-stage lung cancer prediction models. Methods Publications on predictive models of pulmonary nodules/early lung cancer between January 1, 2002 and June 3, 2023 were retrieved and extracted from CNKI, Wanfang, VIP and Web of Science database. CiteSpace 6.1.R3 and VOSviewer 1.6.18 were used to analyze the hotspots and theme trends. Results A marked increase in the number of publications related to pulmonary nodules/early-stage lung cancer prediction models was observed. A total of 12581 authors from 2711 institutions in 64 countries/regions published 2139 documents in 566 academic journals in English. A total of 282 articles from 1256 authors were published in 176 journals in Chinese. The Chinese and English journals which published the most pulmonary nodules/early-stage lung cancer prediction model-related papers were Journal of Clinical Radiology and Frontiers in Oncology, respectively. Chest was the most frequently cited journal. China and the United States were the leading countries in the field of pulmonary nodules/early-stage lung cancer prediction models. The institutions represented by Fudan University had significant academic influence in the field. Analysis of keywords revealed that multi-omics, nomogram, machine learning and artificial intelligence were the current focus of research. Conclusion Over the last two decades, research on risk-prediction models for pulmonary nodules/early-stage lung cancer has attracted increasing attention. Prognosis, machine learning, artificial intelligence, nomogram, and multi-omics technologies are both current hotspots and future trends in this field. In the future, in-depth explorations using different omics should increase the sensitivity and accuracy of pulmonary nodules/early-stage lung cancer prediction models. More high-quality future studies should be conducted to validate the efficacy and safety of pulmonary nodules/early-stage lung cancer prediction models further and reduce the global burden of lung cancer.

Based on the theory of qi， blood and fluids， and taking into account of the pathogenesis evolution process from constraint to phlegm， stasis and then mass in pulmonary nodules， an attempt has been made to construct a three-dimensional differentiation system for pulmonary nodules from the dimensions of time and space. The temporal progression of the early， middle， and late stages of pulmonary nodules reflects the pathological changes from constraint to phlegm and then stasis in the metabolism disorders of qi， blood and fluid. The spatial structures such as size， density， and morphology of pulmonary nodules reflect the pathological states of the duration， severity， and primary and secondary conditions of qi， blood and fluid metabolism disorders. Based on the temporal progression， the therapeutic principles have been proposed， which are dispelling pathogenic factors and promoting the use of beneficial factors to interrupt the growth momentum in the early stage， removing turbidity and dispersing phlegm to reduce the degree of nodules in the middle stage， and dispersing nodulation and eliminating abnormalities in the late stage. Based on the spatial structures， the suggested therapeutic methods are using wind herbs， employing multiple approaches to treat phlegm， and promoting blood circulation to resolve stasis， so as to provide theoretical reference for the systematic diagnosis and treatment of pulmonary nodules in traditional Chinese medicine.

Since the approval of gemtuzumab ozogamicin,an antibody-drug conjugate(ADC)targeting CD33 in 2000,13 ADC drugs have been approved by the FDA.Although these drugs have clearly improved the survival of patients with various types of advanced cancers,their significant toxicity has compromised their therapeutic benefits.The adverse reactions of ADC drugs are complex and include on-target and off-target toxicities,where the payload drug is a determining factor.Antibody and linker may also affect the degree of toxicity.Combination therapy becomes an important strategy in anticancer treatment because of its increased efficiency,but treatment-related adverse reactions also increase accordingly.This review comprehensively analyzes the toxicity mechanisms of current ADC drugs and proposes various optimization strategies,including but not limited to optimizing linker molecules,upgrading antibody design,and changing drug administration strategies,to improve the overall safety profile of ADC drugs.

Purpose: This study identified risk factors for neurogenic lower urinary tract dysfunction (NLUTD) in patients with acute ischemic stroke (AIS) through multidimensional analysis of the medical records of patients, aiming to reduce the incidence of NLUTD, improve prognosis, and facilitate rehabilitation. Materials and Methods: In this case-control study, patients with AIS were recruited from two tertiary general hospitals in Shenzhen, China, from March 2021 to October 2023. Patients were divided into NLUTD and non-NLUTD groups based on the presence and absence of NLUTD, respectively. Comparative analysis was performed using the Mann–Whitney U and chi-square tests, with significant variables being included in logistic regression analysis. Results: Of the 652 participants enrolled in this study, 119 participants (18.3%) developed NLUTD. Bivariate analysis showed that 39 of 54 screened factors exhibited a significant correlation (p<0.05) with the incidence of NLUTD after AIS. Significant variables identified through logistic regression analysis included Glasgow coma scale (GCS) and National Institutes of Health Stroke Scale (NIHSS) scores, anemia, aphasia, pneumonia, brainstem involvement, multiple lesions, urine clarity (CLA), random venous blood glucose (GLU) and hemoglobin (HGB) levels, and white blood cell (WBC) count. Conclusions A total of 11 risk factors for NLUTD were identified in this study. This finding provides valuable guidance for reducing the incidence of NLUTD after AIS and improving the quality of life of patients.

Females increase aggression for mating opportunities and for acquiring reproductive resources. Although the close relationship between female aggression and mating status is widely appreciated, whether and how female aggression is regulated by mating-related cues remains poorly understood. Here we report an interesting observation that Drosophila virgin females initiate high-frequency attacks toward mated females. We identify 11-cis-vaccenyl acetate (cVA), a male-derived pheromone transferred to females during mating, which promotes virgin female aggression. We subsequently reveal a cVA-responsive neural circuit consisting of four orders of neurons, including Or67d, DA1, aSP-g, and pC1 neurons, that mediate cVA-induced virgin female aggression. We also determine that aSP-g neurons release acetylcholine (ACh) to excite pC1 neurons via the nicotinic ACh receptor nAChRα7. Together, beyond revealing cVA as a mating-related inducer of virgin female aggression, our results identify a neural circuit linking the chemosensory perception of mating-related cues to aggressive behavior in Drosophila females.
Animals ; Male ; Female ; Drosophila/physiology* ; Drosophila Proteins/physiology* ; Cues ; Sexual Behavior, Animal/physiology* ; Aggression/physiology* ; Drosophila melanogaster/physiology*

Abnormally activated CDK9 participates in the super-enhancer mediated transcription of short-lived proteins required for cancer cell survival. Targeting CDK9 has shown potent anti-tumor activity in clinical trials among different cancers. However, the study and knowledge on drug resistance to CDK9 inhibitors are very limited. In this study, we established an AML cell line with acquired resistance to a highly selective CDK9 inhibitor BAY1251152. Through genomic sequencing, we identified in the kinase domain of CDK9 a mutation L156F, which is also a coding SNP in the CDK9 gene. By knocking in L156F into cancer cells using CRISPR/Cas9, we found that single CDK9 L156F could drive the resistance to CDK9 inhibitors, not only ATP competitive inhibitor but also PROTAC degrader. Mechanistically, CDK9 L156F disrupts the binding with inhibitors due to steric hindrance, further, the mutation affects the thermal stability and catalytic activity of CDK9 protein. To overcome the drug resistance mediated by the CDK9-L156F mutation, we discovered a compound, IHMT-CDK9-36 which showed potent inhibition activity both for CDK9 WT and L156F mutant. Together, we report a novel resistance mechanism for CDK9 inhibitors and provide a novel chemical scaffold for the future development of CDK9 inhibitors.

Objective: To analyze the epidemiological characteristics and genetic characteristics of sapovirus (SaV) in a cluster of schools in Changzhou, so as to provide a reference for the treatment of clustered vomiting and diarrhea events in schools. Methods: The epidemiological data and laboratory test data of sapovirus clusters in Changzhou from 2019 to 2022 were collected and analyzed. Partial VP1 genes of SaV positive samples were amplified and sequenced for phylogenetic analysis. Results: A total of 8 cases of clusters of SaV epidemics were reported in Changzhou City from 2019 to 2022, with 118 reported cases. The total attack rate was 1.47%, and the median of the attack number was 15. There were 6 outbreaks in kindergartens and 2 outbreaks in primary schools, which were reported in the epidemic period from September to December. The main clinical manifestations were vomiting (113 cases, 95.76 %), abdominal pain (39 cases, 33.05%), and diarrhea (16 cases, 13.56%). Among the 8 outbreaks, 17 sample strains were successfully sequenced. 5 outbreaks were GII.3 , and the other 3 outbreaks were GI.1, GI .3 and GII.2. GI and GII were the main genotypes in this area, and GII .3 was the predominant strain. Conclusion SaV is an important pathogen in the clusters of vomiting and diarrhea in schools after the transmission of norovirus. Continuous surveillance of SaV should be carried out to further understand its epidemiological characteristics and genotype distribution, so as to provide scientific basis for the prevention and control of the epidemic in schools.

During the carcinoma transformation of colitis， the imbalance of “metabolic-immune interaction” resulted from abnormal energy and metabolic substrates flow and direction was the key process， which caused by intercellular metabolic competition. Based on traditional Chinese medicine （TCM） theory and clinical research， we found that “fire failing to warm earth” is the key pathogenesis of colon-cancer transformation. “Fire” was a synonym for TCM to understand the energy metabolism， combined modern medical research findings， we thought energy metabolism disorders was a microcosmic manifestation of the “fire decline”， while abnormal immune function was the biological basis of “earth deficiency”. The imbalance between “metabolism-immune interaction” and the “fire failing to warm earth” pathogenesis of colitis-cancer transformation demonstrated the different understanding of the same pathological mechanism between western medicine and TCM. For treatment， it could be effectivce to delay the transformation of colitis-cancer by synergistically regulated the energy metabolism - “replenish fire” and enhanced the immune function - “nourish earth”， which was called the methods of replenishing fire to nourish earth.

Pulmonary nodule is a key window for moving ahead the diagnosis and treatment of lung cancer. Traditional Chinese medicine （TCM） can delay the transformation of lung nodules into lung cancer， improve the prognosis of patients， effectively fill the treatment gap during the follow-up period of pulmonary nodules， and has been applied it in the whole cycle and multi-dimensional management of pulmonary nodules. This paper discussed the construction ideas and feasible paths of the whole process management diagnosis and treatment system of pulmonary nodules in TCM， proposed the diagnosis and treatment database of TCM for pulmonary nodules based on the social module of “family-community-hospital”. Through artificial intelligence， we can develop， improve and promote the multi-level and multi-modal “disease-symptom combination” risk prediction model and effectiveness evaluation system of pulmonary nodules. At the same time， the biological connotation of the prevention and treatment of pulmonary nodules by TCM is excavated， which provided empirical evidence for the construction of TCM diagnosis and treatment system， in order to further improve the quality and diagnosis and treatment level of the whole course management of pulmonary nodules.

Objective:To analyze clinical manifestations, pathological features and prognosis of patients with stage Ⅰ cutaneous melanoma.Methods:Clinical data were collected from 163 patients with stage Ⅰ cutaneous melanoma in Department of Dermatology, Xijing Hospital from January 2010 to January 2020, and clinical manifestations, pathological features, treatment methods and prognosis were retrospectively analyzed.Results:Among the 163 patients with stage Ⅰ cutaneous melanoma, 56 (34.36%) were males, and 107 (65.64%) were females, with a median age of 53 years at the clinic visit. Primary skin lesions were most frequently located on the extremities in 104 cases (63.80%) , of which 39 presented with lesions on the finger or toe nails and 65 with lesions on the other parts of the extremities; skin lesions were located at sun-exposed sites such as the head and face in 29 (17.79%) cases, and at non-sun-exposed sites such as the trunk and extremities except the hands and feet in 30 (18.40%) . Of the 163 patients, 56 (34.36%) were pathologically diagnosed with stage ⅠA cutaneous melanoma, and 107 (65.64%) with stage ⅠB cutaneous melanoma. According to a pathological staging system, 104 (63.80%) patients suffered from acral lentiginous melanoma, 23 (14.11%) superficial spreading melanoma, 15 (9.20%) nodular melanoma, 14 (8.59%) malignant lentigo-maligna melanoma, and 7 (4.29%) other rare or difficult-to-determine types. All the 163 patients received surgical treatment at least once, of whom 15 underwent finger or toe amputation, 94 extended resections, and 54 unextended resections; 35 received secondary surgeries, of whom 33 underwent extended resections and 2 finger amputation. Seven patients developed postoperative lymph node and/or distant organ metastases, 2 of whom died after distant organ metastases. The 5-year survival rate of the 163 patients was 98.00%.Conclusion:Stage Ⅰ cutaneous melanoma commonly has favorable prognosis, and 7 patients developed postoperative lymph node and/or distant organ metastases in this study, suggesting that long-term follow-up of patients with acral melanoma and early intervention of those with metastatic melanoma should be strengthened.