ObjectiveTo investigate the characteristics and distribution of traditional Chinese medicine （TCM） syndromes in the patients with esophageal squamous cell carcinoma （ESCC）. MethodsAn electronic questionnaire was developed to collect the general data and four examination information of ESCC patients treated in 10 areas with high incidence of esophageal cancer in China from June 2020 to March 2021. Multiple analyses including frequency analysis， factor analysis， and hierarchical cluster analysis were performed to analyze the potential syndrome elements， disease location， and common syndromes of ESCC. ResultsA total of 2 027 patients with ESCC were included. Statistical analysis was performed on 113 symptoms， physical signs， 33 tongue manifestation variables， and 23 pulse manifestation variables of the patients’ four examination information. Factor analysis was performed on 55 variables with frequency>10%， extracting 19 common factors. According to clinical experience and expert opinions， the main lesions of patients with ESCC were in the spleen and stomach， and the main syndrome elements were Qi stagnation， blood stasis， phlegm， dampness， and Qi deficiency， with the syndrome element combination of phlegm obstruction + Qi stagnation + blood stasis being the most common. The syndromes can be classified into four categories of liver-stomach disharmony + combined phlegm and Qi obstruction， kidney-spleen dysfunction + combined phlegm and stasis， spleen-kidney Yang deficiency + obstinate phlegm and blood stasis， and liver-kidney Yin deficiency + obstinate phlegm and blood stasis. The main syndrome of ESCC was liver-stomach disharmony + combined phlegm and Qi obstruction in the early stage， liver-spleen dysfunction + combined phlegm and stasis in the middle stage， and spleen-kidney Yang deficiency + obstinate phlegm and blood stasis in the late stage. ConclusionESCC mainly has main pathological features of internal deficiency and external excess and combined deficiency and excess， with the key syndrome elements being phlegm obstruction， Qi stagnation， and blood stasis. The main disease locations are in the spleen and stomach， involving the liver， kidney， chest and diaphragm， heart， and lung. The main syndrome is liver-stomach disharmony + combined phlegm and Qi obstruction. In clinical practice， it is necessary to grasp the pathogenesis dynamics of the disease and use prescriptions according to patients’ syndromes.

The aging microenvironment, as a key driver of tumorigenesis and progression, plays a critical role in tumor immune regulation through one of its core features-the senescence-associated secretory phenotype (SASP). SASP consists of a variety of interleukins, chemokines, proteases, and growth factors. It initially induces surrounding cells to enter a state of senescence through paracrine mechanisms, thereby creating a sustained inflammatory stimulus and signal amplification effect within the tissue microenvironment. Furthermore, these secreted factors activate key signaling pathways such as NF-κB, cGAS-STING, and mTOR, which regulate the expression of immune-related molecules (such as PD-L1) and promote the recruitment of immunosuppressive cells, including regulatory T cells and myeloid-derived suppressor cells. This process ultimately contributes to the formation of an immunosuppressive tumor microenvironment. Furthermore, the article explores potential anti-tumor immunotherapy strategies targeting SASP and its associated molecular mechanisms, including approaches to inhibit SASP secretion or eliminate senescent cells. Although these strategies have shown promise in certain tumor models, the high heterogeneity among tumor types may result in varied responses to SASP-targeted therapies. This highlights the need for further research into adaptive stratification and personalized treatment approaches. Targeting immune regulatory mechanisms in the aging microenvironment-particularly SASP-holds great potential for advancing future anti-tumor therapies.

Protein liquid-liquid phase separation (LLPS), a pivotal phenomenon intricately linked to cellular processes, is regulated by various other proteins. However, there is still a lack of high-throughput methods for screening protein regulators of LLPS in target proteins. Here, we developed a CRISPR/Cas9-based screening method to identify protein phase separation regulators by integrating bimolecular fluorescence complementation (BiFC) and fluorescence-activated cell sorting (FACS). Using this newly developed method, we screened the RNA-binding proteins that regulate PABPN1 phase separation and identified the tumor suppressor QKI as a promoter of PABPN1 phase separation. Furthermore, QKI exhibits decreased expression levels and diminished nuclear localization in colorectal cancer cells, resulting in reduced PABPN1 phase separation, which, in turn, promotes alternative polyadenylation (APA), cell proliferation, and migration in colorectal cancer.
Humans ; Colorectal Neoplasms/genetics* ; RNA-Binding Proteins/genetics* ; Poly(A)-Binding Protein I/genetics* ; CRISPR-Cas Systems ; Flow Cytometry ; Cell Proliferation ; Cell Line, Tumor ; Cell Movement

Aldehyde oxidase (AOX) is a molybdoenzyme that is primarily expressed in the liver and is involved in the metabolism of drugs and other xenobiotics. AOX-mediated metabolism can result in unexpected outcomes, such as the production of toxic metabolites and high metabolic clearance, which can lead to the clinical failure of novel therapeutic agents. Computational models can assist medicinal chemists in rapidly evaluating the AOX metabolic risk of compounds during the early phases of drug discovery and provide valuable clues for manipulating AOX-mediated metabolism liability. In this study, we developed a novel graph neural network called AOMP for predicting AOX-mediated metabolism. AOMP integrated the tasks of metabolic substrate/non-substrate classification and metabolic site prediction, while utilizing transfer learning from ¹³C nuclear magnetic resonance data to enhance its performance on both tasks. AOMP significantly outperformed the benchmark methods in both cross-validation and external testing. Using AOMP, we systematically assessed the AOX-mediated metabolism of common fragments in kinase inhibitors and successfully identified four new scaffolds with AOX metabolism liability, which were validated through in vitro experiments. Furthermore, for the convenience of the community, we established the first online service for AOX metabolism prediction based on AOMP, which is freely available at https://aomp.alphama.com.cn.

Vertebrobasilar dolichoectasia is a rare and challenging disorder. Vertebrobasilar dolichoectasia is closely related to enzyme action and hemodynamic changes, and is characterized by ischemic stroke, neurological compression symptoms, hydrocephalus, and other clinical symptoms. With development of interventional techniques and materials in recent years, endovascular treatment of vertebrobasilar dolichoectasia has become the focus. This article summarizes the current endovascular treatment of vertebrobasilar dolichoectasia, aiming to provide references for clinicians.

This paper summarized Professor LI Haisong's clinical experience in treating spermatorrhea based on the view of "spirit controlling essence and qi". It is emphasized that the heart spirit has the function of controlling the essence and qi of the human body， believing the frenetic stirring of heart spirit and the insecurity of essence gate are the core pathogenesis of spermatorrhea， LI advocates to regulate the heart spirit first and take into account of the zang-fu organs， essence and qi simultaneously for the treatment. Treatment should be performed according the clinical syndromes differentiatied. For those with heart spirit failing to nourish syndrome， it is recommended to supplement heart qi， nourish spirit and consolidate essence with self-made Yangxin Mijing Formula （养心秘精方）. In case of heart fire hyperactivity， the method of clearing heart heat and draining fire， calming spirit and consolidating essence should be used， and self-made Xiexin Gujing Formula （泻心固精方） is recommended. For heart-liver qi constraint， it is advised to soothe the liver and calm heart， calm the mind and regulate essence with self-made Jieyu Anshen Tiaojing Formula （解郁安神调精方） which is a modifcation to Chaihu Shugan Powder （柴胡疏肝散）. In terms of deficiency of both heart and liver， the treatment principle is supplementing spleen and nourishing heart， calming the mind and controlling essence， for which self-made Xinpi Tongtiao Shejing Formula （心脾同调摄精方） modified from Guipi Decoction （归脾汤） can be used. For deficiency of both heart and kidney， it is better to nourish the kidney and calm heart， calm the mind and consolidate essence with self-made Xinshen Liangzi Tianjing Formula （心肾两滋填精方） that modified from Shuilu Erxian Elixir （水陆二仙丹） and Wuzi Yanzong Pill （五子衍宗丸）. Prescriptions are used to treat the root by harmonizing the zang-fu organs， nourish the spirit by regulating qi and blood， and calm the mind by taking special medi-cinals， and they should be flexibly modified according to the disease.

ObjectiveTo construct traditional Chinese medicine （TCM） diagnostic scale of turbid toxin syndrome in order to provide corresponding reference for the standardization of TCM syndromes and studies. MethodsWe systematically searched the Chinese Medical Dictionary （CMD）， China Knowledge Network （CNKI）， Wanfang Data Knowledge Service Platform （WF） and VIP database for TCM classics and modern literature on turbid toxin syndrome， and initially screened the four diagnosis information of turbid toxin syndrome， established a pool of information entries， and conducted a cross-sectional clinical survey. Discrete trend method， correlation coefficient method， Cronbach's coefficient method， and factor analysis method were applied to objectively screen the entries. The diagnostic scale of turbid toxin syndrome were constructed through three rounds of Delphi method expert survey to determine the scale entries， using hierarchical analysis to get the judgement matrix scores and relative weight of each entry， after passing consistency test and then isometric expansion of the relative weight of the entries to get the weight of each entry and assign the value. ResultsA total of 35 articles were included， 45 entries were obtained after the initial screening. After the clinical investigation， 12 entries were not suitable by the discrete trend method， 23 entries not suitable by correlation coefficient method， 13 entries by the internal consistency screening were removed with the Cronbach's alpha coefficient rising， and 10 entries not suitable by the factor analysis method. Twenty-two entries were retained after objective screening by the combined use of the four statistical methods. The positive coefficients of experts in the three rounds of Delphi method of expert consultation were 96.67%， the coefficients of expert authority were 0.834， 0.856， and 0.867， and the coefficients of co-ordination were 0.126， 0.326， and 0.312， respectively. After consulting with clinical experts， and three rounds of Delphi method survey and hierarchical analysis method weight assignment， the diagnostic scale entries of turbid toxin syndrome were finally established. Primary symptoms： dark red or purple and dusky tongue， yellowish greasy or dry coating （10 points）； sticky and unpleasant stools （8 points）； disharmony of tastes including halitosis， sticky and greasy taste in the mouth， dry mouth and bitter taste in the mouth （6 points）； unfavourable or yellowish or red urination （5 points）； and dark complexion （4 points）. Secondary symptoms： heavy body （3 points）； dizziness （3 points）； profuse， sticky， foul-smelling secretions （2 points）； wiry and slippery， or slippery， or slippery and rapid pulse （2 points）； feeling of hardness in the abdomen （1 point）. ConclusionUsing Delphi method combined with the hierarchical analysis method， combining qualitative and quantitative study， a diagnostic scale of turbid toxin syndrome was initially developed.

Objective This study investigated the epidemic characteristics and spatio-temporal dynamics of hemorrhagic fever with renal syndrome (HFRS) in Qingdao City,China. Methods Information was collected on HFRS cases in Qingdao City from 2010 to 2022. Descriptive epidemiologic,seasonal decomposition,spatial autocorrelation,and spatio-temporal cluster analyses were performed. Results A total of 2,220 patients with HFRS were reported over the study period,with an average annual incidence of 1.89/100,000 and a case fatality rate of 2.52％. The male:female ratio was 2.8:1. 75.3％ of patients were aged between 16 and 60 years old,75.3％ of patients were farmers,and 11.6％ had both "three red" and "three pain" symptoms. The HFRS epidemic showed two-peak seasonality:the primary fall-winter peak and the minor spring peak. The HFRS epidemic presented highly spatially heterogeneous,street/township-level hot spots that were mostly distributed in Huangdao,Pingdu,and Jiaozhou. The spatio-temporal cluster analysis revealed three cluster areas in Qingdao City that were located in the south of Huangdao District during the fall-winter peak. Conclusion The distribution of HFRS in Qingdao exhibited periodic,seasonal,and regional characteristics,with high spatial clustering heterogeneity. The typical symptoms of "three red" and"three pain" in patients with HFRS were not obvious.

Objective:To observe the toxic and side effects of TCM syndrome differentiation and treatment combined with abemaciclib and endocrine drugs in the treatment of hormone receptor ( HR ) positive and human epidermal growth factor receptor 2 ( HER2 ) negative advanced breast cancer and the dose of abemaciclib under the influence of toxic and side effects.Methods:Patients with HR+/HER2- advanced breast cancer who received TCM combined with abemaciclib and endocrine therapy in Beijing Hospital of Traditional Chinese Medicine, Capital Medical University from March 2021 to February 2023 were selected, and the relevant data of East Asian population in MONARCH 2 and MONARCH 3 of abemaciclib random phase Ⅲ clinical study were extracted for retrospective cohort study. The TCM exposure cohort was divided into 20 cases of TCM + abemaciclib + fulvestrant group (EXP 1) and 22 cases of TCM + abemaciclib + aromatase inhibitor (AI) group (EXP 2). The East Asian populations in MONARCH 2 and 3 were non-exposed cohorts, which were divided into NEXP 1 group ( 146 cases ) and NEXP 2 group (102 cases). The safety analysis of the 2 cohorts was carried out, and the reduction and termination of abemaciclib taken by patients under the influence of toxic and side effects were counted.Results:①There were significant differences in CTCAE any grade, grade 2 ( χ2 values were 8.11, 4.59, respectively ) between EXP 1 group and NEXP 1 group, as well as in CTCAE any grade ( χ2=18.57) between EXP 2 group and NEXP 2 group compare the incidence rate of diarrhoea ( P<0.05 or P<0.01). There was significant differences in CTCAE ≥ grade 2 EXP 1 group compare the incidence rate of diarrhoea ( χ2=5.56, P=0.02). The incidence of grade ≥ 3 neutropenia in EXP 1 was [ 5 cases (27.78%) ] and in EXP 2 was [ 2 cases (13.33%)]. There were 65 cases (44.52%) in NEXP 1 and 30 cases (29.41%) in NEXP 2, and the exposed cohort were lower than those in the non-exposed cohort. The increase of GPT, GOT and SCr in the exposed cohort were lower than those in the non-exposed cohort. ② Compared with the non-exposed cohort, the first occurrence time of diarrhea and neutropenia was prolonged and the duration was shortened in the exposed cohort. ③ The patients in the exposed cohort were less likely to take abemaciclib reduction and discontinuation due to diarrhea, neutropenia, impaired liver function, and elevated SCr than those in the non-exposed cohort. Conclusion:TCM syndrome differentiation and treatment combined with abemaciclib and endocrine drugs is safe in the treatment of HR+/HER2- advanced breast cancer, which can effectively prevent and treat the toxic and side effects caused by abemaciclib, and reduce the drug reduction and discontinuation.

Objective To explore the correlation between left atrial diameter (LAD) and renal function in patients with atrial fibrillation. Methods A total of 364 patients with atrial fibrillation were selected as study subjects. Clinical data of the patients were collected, including gender, age, height, body weight, smoking history, drinking history, atrial fibrillation type, history of hypertension, coronary heart disease, diabetes, heart failure, medication history, high-sensitivity troponin I, brain natriuretic peptide, C-reactive protein, creatinine, urea nitrogen, LAD, left ventricular ejection fraction (LVEF), left ventricular end-diastolic diameter (LVDd), left ventricular posterior wall thickness (LVPWTd), and interventricular septal thickness (IVSTd). Estimated glomerular filtration rate (eGFR) and body mass index were calculated. Spearman correlation analysis was used to explore the correlations of LAD with creatinine, urea nitrogen, and eGFR. With eGFR < 60 mL/(min·1.73 m²) setting as renal insufficiency, univariate Logistic regression analysis was used to explore the influencing factors of renal insufficiency in patients with atrial fibrillation. Binary Logistic regression analysis was used to explore the relationship between LAD and renal insufficiency in patients with atrial fibrillation. Results Spearman correlation analysis showed that LAD was positively correlated with creatinine (r=0.279, P < 0.001) and urea nitrogen (r=0.190, P < 0.001) in patients with atrial fibrillation, and negatively correlated with eGFR (r=-0.263, P < 0.001). Univariate Logistic regression analysis showed that gender, history of diabetes, hypertension, coronary heart disease, heart failure, atrial fibrillation type, sodium-glucose cotransporter 2 inhibitor medication history, diuretic medication history, LAD, LVEF, LVDd, and IVSTd were all influencing factors of renal insufficiency in patients with atrial fibrillation (P < 0.05). Binary Logistic regression analysis showed that compared with the first quartile of LAD (LAD ≤ 38 mm), the risk of renal insufficiency in patients with atrial fibrillation in the fourth quartile of LAD (LAD>47 mm) increased by 5.199 times(OR=5.199; 95 %CI, 1.210 to 22.337; P=0.027). Conclusion LAD of patients with atrial fibrillation is significantly related to renal function, and LAD is an influencing factor of renal insufficiency in patients with atrial fibrillation.