The chronicity of infectious diseases is an important field in the collaborative research of traditional Chinese and Western medicine. The warm disease theory of pathogen invading nutrient and blood aspects in traditional Chinese medicine （TCM） takes the struggle between healthy Qi and pathogenic Qi and cementation of Yin as the core pathogenesis， providing a unique theoretical framework for explaining the common pathology of infectious chronic diseases. This theory originated from Yin-Yang interaction in the Internal Classic and was enriched with WU Youke's theory of intruding pathogen interacting and lingering in blood vessels and YE Tianshi's theory of long-term illness entering collaterals. Combining the theory with modern medical knowledge， our team has condensed the dynamic pathogenesis model of deficiency （nutrient and blood aspects） and excess （pathogen） interacting in the blood collaterals of Yin aspect， the core feature of which is the four-dimensional interactions of cause （pathogen characteristics）， location （three Yin locations of diseases）， nature （deficiency and excess）， and potential （transmission trend）. The common pathology of infectious chronic diseases is reflected in interactions. That is， the interactions between nutrient and blood deficiency （immune exhaustion and metabolic disorder） and pathogen excess （pathogen persistence and fibrous hyperplasia） in the liver collaterals （Jueyin）， kidney collaterals （Shaoyin）， lung collaterals （Taiyin） and other blood collaterals of Yin aspect form the pathological damage characterized by immune inflammatory response-continuous tissue damage with excessive repair. Taking the inheritance and innovative development of classics as the main line， this paper systematically discusses the scientific connotation of the theory of pathogen invading nutrient and blood aspects and the paths of inheritance and innovation and clarifies the original significance of this theory in the chronic development of infectious diseases. Furthermore， taking clinical diseases as an example， this paper reflects the guiding value of this classical theory in the modern diagnosis and treatment of infectious diseases with integrated traditional Chinese and Western medicine and the application potential of this theory in solving complex medical problems through the construction of the innovative paradigm of precise diagnosis and treatment with integrated traditional Chinese and Western medicine.

Hepatocellular carcinoma （HCC）， a malignancy with high mortality， exhibits poor survival rates and prognosis. The profound suppression of the tumor immune microenvironment （TIME） and the abnormal hyperactivity of metabolic reprogramming （MR） are the two primary factors driving HCC progression. Traditional Chinese medicine has demonstrated significant efficacy in HCC treatment. The team proposed that "deficiency of healthy Qi and stasis toxins" was the core pathogenesis of HCC， closely associated with TIME suppression and MR hyperactivity. This paper proposed that a suppressed state of the TIME was the biological manifestation of "deficiency of healthy Qi"， where the functional exhaustion of effector T lymphocytes and natural killer cells reflected the decline of "healthy Qi" in eliminating pathogens. Conversely， the expansion and activation of immunosuppressive cells， such as regulatory T cells （Tregs）， M2-like tumor-associated macrophages （TAM-M2）， and myeloid-derived suppressor cells （MDSCs） ， represent the dysfunction of "healthy Qi" in maintaining homeostasis. MR serves as the material basis of "stasis toxins". Stasis toxins exhibit heat stagnation， manifested by abnormal hyperactivity of glycolysis and lipid synthesis. They demonstrate migratory propensity， as toxic metabolites like lactic acid and prostaglandin E2 promote tumor invasion and metastasis. They display a consumptive nature， reflected in the functional suppression of immune cells. The vicious cycle between TIME and MR is the biopathological reflection of "deficiency of healthy Qi intertwined with stasis toxins". Immunosuppression exacerbates MR， while toxic metabolites further impair immune function， establishing a pathogenic chain of "deficiency leading to stasis， and stasis toxins damaging healthy Qi". The primary therapeutic approach is reinforcing healthy Qi， resolving stasis， and removing toxins， which can reinforce and tonify healthy Qi to regulate pathways， such as phosphatidylinositol 3-kinase/protein kinase B （PI3K/Akt）， C-X-C chemokine receptor type 4/ C-X-C chemokine ligand 12 （CXCR4/CXCL12）， and toll-like receptor 4/ nuclear factor-kappa B/ signal transducer and activator of transcription 3 （TLR4/NF-κB/STAT3）， adjust T lymphocyte ratios， inhibit Tregs/TAM-M2 function， and downregulate immune checkpoints， including programmed death ligand 1/programmed death 1（PD-L1/PD-1）， and reshape TIME. It is also involved in resolving stasis and removing toxins to modulate phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin （PI3K/Akt/mTOR） and hypoxia-inducible factor-1α （HIF-1α） signaling pathways， suppress key enzymes in glycolysis and lipid synthesis， and block toxic metabolite production. Thus， this therapy synergistically regulates the immune and metabolic network， breaks the vicious cycle of "deficiency in healthy Qi and stasis toxins"， and offers a novel strategy for integrating traditional Chinese medicine and Western medicine in HCC treatment.

Gene regulation relies on the precise binding of transcription factors (TFs) at regulatory elements, but simultaneously detecting hundreds of TFs on chromatin is challenging. We developed cFOOT-seq, a cytosine deaminase-based TF footprinting assay, for high-resolution, quantitative genome-wide assessment of TF binding in both open and closed chromatin regions, even with small cell numbers. By utilizing the dsDNA deaminase SsdAtox, cFOOT-seq converts accessible cytosines to uracil while preserving genomic integrity, making it compatible with techniques like ATAC-seq for sensitive and cost-effective detection of TF occupancy at the single-molecule and single-cell level. Our approach enables the delineation of TF footprints, quantification of occupancy, and examination of chromatin influences on TF binding. Notably, cFOOT-seq, combined with FootTrack analysis, enables de novo prediction of TF binding sites and tracking of TF occupancy dynamics. We demonstrate its application in capturing cell type-specific TFs, analyzing TF dynamics during reprogramming, and revealing TF dependencies on chromatin remodelers. Overall, cFOOT-seq represents a robust approach for investigating the genome-wide dynamics of TF occupancy and elucidating the cis-regulatory architecture underlying gene regulation.
Transcription Factors/genetics* ; Humans ; Chromatin/genetics* ; Animals ; Binding Sites ; Mice ; DNA Footprinting/methods*

Guided by molecular networking, nine novel curvularin derivatives (1-9) and 16 known analogs (10-25) were isolated from the hydrothermal vent sediment fungus Penicillium sp. HL-50. Notably, compounds 5-7 represented a hybrid of curvularin and purine. The structures and absolute configurations of compounds 1-9 were elucidated via nuclear magnetic resonance (NMR) spectroscopy, X-ray diffraction, electronic circular dichroism (ECD) calculations, ¹³C NMR calculation, modified Mosher's method, and chemical derivatization. Investigation of anti-inflammatory activities revealed that compounds 7-9, 11, 12, 14, 15, and 18 exhibited significant suppressive effects against lipopolysaccharide (LPS)-induced nitric oxide (NO) production in murine macrophage RAW264.7 cells, with IC₅₀ values ranging from 0.44 to 4.40 μmol·L^-1. Furthermore, these bioactive compounds were found to suppress the expression of inflammation-related proteins, including inducible NO synthase (iNOS), cyclooxygenase-2 (COX-2), NLR family pyrin domain-containing protein 3 (NLRP3), and nuclear factor kappa-B (NF-κB). Additional studies demonstrated that the novel compound 7 possessed potent anti-inflammatory activity by inhibiting the transcription of inflammation-related genes, downregulating the expression of inflammation-related proteins, and inhibiting the release of inflammatory cytokines, indicating its potential application in the treatment of inflammatory diseases.
Penicillium/chemistry* ; Mice ; Animals ; Anti-Inflammatory Agents/isolation & purification* ; RAW 264.7 Cells ; Nitric Oxide/metabolism* ; Hydrothermal Vents/microbiology* ; Macrophages/immunology* ; Molecular Structure ; Nitric Oxide Synthase Type II/immunology* ; Cyclooxygenase 2/immunology* ; Geologic Sediments/microbiology* ; NF-kappa B/immunology* ; NLR Family, Pyrin Domain-Containing 3 Protein/immunology*

The timely use of screening tools to assess the palliative care needs of emergency patients can provide decision-making basis for patient referral and help patients receive palliative care in a timely manner.This paper reviews the palliative care needs screening tools for emergency patients at home and abroad,describes their development methods,scoring criteria and application status,compares and analyzes their characteristics and shortcomings.It aims to provide references for the localized development and application of palliative care needs screening tools in emergency patients.

Background::Endovascular abdominal aortic aneurysm repair (EVAR) is the major treatment for abdominal aortic aneurysm (AAA); however, EVAR still carries a considerable risk of acute kidney injury (AKI). The present study aimed to investigate the risk factors for AKI after elective EVAR procedures.Methods::This was a retrospective observational study. Eligible patients who underwent EVAR from September 2011 to March 2019 in West China Hospital were included. The primary outcome was the occurrence of AKI within two days after EVAR, which was defined by the Kidney Disease Improving Global Outcomes Clinical Practice Guideline. Demographics, comorbidities, medications, laboratory tests, anatomical parameters of AAA, and relative operative details were collected as variables. Univariable and multivariable logistic regression analyses were applied to identify the risk factors among variables, and covariate interactions were further assessed.Results::A total of 679 eligible patients were included. The incidence of postoperative AKI was 8.2% (56/679) in the whole cohort, and it was associated with a lower 5-year survival rate (63.5% vs. 80.9%; χ2 = 4.10; P = 0.043). The multivariable logistic regression showed that chronic kidney disease (OR, 5.06; 95% CI: 1.43-17.95; P = 0.012), angiotensin-converting enzyme inhibitors (ACEIs)/angiotensin receptor blockers (ARBs) (OR, 2.60; 95% CI: 1.17-5.76; P = 0.019), and short neck (OR, 2.85; 95% CI: 1.08-7.52; P = 0.035) were independent risk factors for postoperative AKI. In the covariate interaction analysis, the effect of ACEIs/ARBs use on postoperative AKI was similar across all subgroups ( P > 0.05), thereby suggesting a robust effect of ACEIs/ARBs use in all patients undergoing elective endovascular abdominal aortic aneurysm repair. Conclusions::Postoperative AKI was associated with lower survival rate, and the use of ACEIs/ARBs was the only adjustable independent risk factor. Clinicians should consider withdrawing ACEIs/ARBs in high-risk patients undergoing elective endovascular abdominal aortic aneurysm repair to prevent postoperative AKI.

3D printing technology has been widely applied in the field of clinical education in vascular surgery due to the advantage of 100% reduction of objects. Vascular surgeons with different levels benefit from 3D printing application in anatomy structure, operation plan, skill training with simulator. At present, the application of 3D printing model in vascular surgery is still in the initial stage with some limitations. This paper reviews the application, limitations, and prospects of 3D printing model in clinical teaching of vascular surgery.

Objective: The phenotype and genetics of three patients with autosomal recessive polycystic kidney disease (ARPKD) at childhood, teenage and advanced age were analyzed. Methods: Next generation sequencing (NGS) was applied to all the probands. PCR and Sanger sequencing were used to verify the suspicious gene variants screened by NGS in the probands and their family members, and one of the family got prenatal diagnosis. Results: Through NGS, PCR and Sanger sequencing, the 5-yr proband in pedigree 1 was shown to carry compound heterozygous variants of c. 5935G>A(p.G1979R) and c. 5428G>T(p.E1810X) of PKHD1, originated from his parents; In pedigree 2, the 17-ys proband was detected with c. 5512T>C(p.Y1838H) and c. 5935G>A(p.G1979R) variants of PKHD1 orginated from her parents, and her mother also got prenatal diagnosis during the second trimester; In pedigree 3, the 70-ys female proband was found with variants c. 11314C>T (p.R3772X) and c. 3860T>G (p.V1287G) of PKHD1. Conclusion The three pedigrees were diagnosed as ARPKD caused by PKHD1 variants. Five types of variants were detected, c. 5935G>A and c. 11314C>T were the known pathogenic variants, while c. 5512T>C, c. 5428G>T and c. 3860T>G were not reported previously. Considering the complexity of the genetics and phenotypes of the cystic renal diseases, genetic diagnosis is crucial to give accurate etiological diagnosis, which may benefit the clinic management.

Norovirus, as one of the main pathogens causing non-bacterial gastroenteritis, can cause serious public health problems and economic losses around the world. In recent years, the outbreaks caused by the virus in China are on the rise. Human Norovirus (HuNoV) can hardly be cultivated in-vitro. The nucleic acid detection method (such as RT-qPCR) has the highest sensitivity and specificity, but it was not established that the correlation between the detected viral genome and viral infectivity, which leads to inaccurate judgment of safety risks. Here, the in-vitro and in-vivo culture models, viral genome integrity and capsid protein integrity were cut into three aspects. The research progress and characteristics of infectious Norovirus identification technology in recent years were reviewed and discussed, and the future development trend of this technology was prospected. The aim is to further improve the accuracy of Norovirus quantitative detection and provide a theoretical basis for its application in the field of food safety testing.

OBJECTIVE: To explore the clinical features and genetic diagnosis of two cases with rare diseases and X chromosome abnormalities. METHODS: Multiple ligation-dependent probe amplification (MLPA) and karyotype analysis were carried out on an 8-year-old girl who was diagnosed with Duchenne muscular dystrophy. Karyotype analysis and PCR assay for SRY and AZF genes were carried out for a-2-month-old male infant with short penis. RESULTS: The girl, who featured short stature and cubitus valgus, was diagnosed as Turner syndrome with a karyotype of 46,X,i(Xq). The male infant was detected with a karyotype of 45,X, with presence of SRY gene but absence of AZF gene. CONCLUSION Both cases may be associated with abnormalities of X chromosome. Genetic testing can facilitate early diagnosis and clinical intervention for such patients.
Chromosomes, Human, X ; Humans ; Infant ; Karyotyping ; Male ; Muscular Dystrophy, Duchenne ; genetics ; Rare Diseases ; Turner Syndrome ; genetics