ObjectiveTo develop a predictive model and application for spontaneous passage of common bile duct stones using automated machine learning algorithms given the complexity of treatment decision-making for patients with common bile duct stones， and to reduce unnecessary endoscopic retrograde cholangiopancreatography （ERCP） procedures. MethodsA retrospective analysis was performed for the data of 835 patients who were scheduled for ERCP after a confirmed diagnosis of common bile duct stones based on imaging techniques in Changshu First People’s Hospital （dataset 1） and Changshu Traditional Chinese Medicine Hospital （dataset 2）. The dataset 1 was used for the training and internal validation of the machine learning model and the development of an application， and the dataset 2 was used for external testing. A total of 22 potential predictive variables were included for the establishment and internal validation of the LASSO regression model and various automated machine learning models. The area under the receiver operating characteristic curve （AUC）， sensitivity， specificity， and accuracy were used to assess the performance of models and identify the best model. Feature importance plots， force plots， and SHAP plots were used to interpret the model. The Python Dash library and the best model were used to develop a web application， and external testing was conducted using the dataset 2. The Kolmogorov-Smirnov test was used to examine whether the data were normally distributed， and the Mann-Whitney U test was used for comparison between two groups， while the chi-square test or the Fisher’s exact test was used for comparison of categorical data between groups. ResultsAmong the 835 patients included in the study， 152 （18.20%） experienced spontaneous stone passage. The LASSO model achieved an AUC of 0.875 in the training set （n=588） and 0.864 in the validation set （n=171）， and the top five predictive factors in terms of importance were solitary common bile duct stones， non-dilated common bile duct， diameter of common bile duct stones， a reduction in serum alkaline phosphatase （ALP）， and a reduction in gamma-glutamyl transpeptidase （GGT）. A total of 55 models were established using automated machine learning， among which the gradient boosting machine （GBM） model had the best performance， with an AUC of 0.891 （95% confidence interval： 0.859‍ ‍—‍ ‍0.927）， outperforming the extreme randomized tree mode， the deep learning model， the generalized linear model， and the distributed random forest model. The GBM model had an accuracy of 0.855， a sensitivity of 0.846， and a specificity of 0.857 in the test set （n=76）. The variable importance analysis showed that five factors had important influence on the prediction of spontaneous stone passage， i.e.， were solitary common bile duct stones， non-dilated common bile duct， a stone diameter of <8 mm， a reduction in serum ALP， and a reduction in GGT. The SHAP analysis of the GBM model showed a significant increase in the probability of spontaneous stone passage in patients with solitary common bile duct stones， non-dilated common bile duct， a stone diameter of <8 mm， and a reduction in serum ALP or GGT. ConclusionThe GBM model and application developed using automated machine learning algorithms exhibit excellent predictive performance and user-friendliness in predicting spontaneous stone passage in patients with common bile duct stones. This application can help avoid unnecessary ERCP procedures， thereby reducing surgical risks and healthcare costs.

Conjunctival lymphangiectasia is a low-incidence ocular surface disease that is currently rarely reported in the relevant literature. It may be related to cosmetic eyelid surgery, tumor, radiation or chemotherapy and other factors and often causes a foreign body sensation, lacrimation, eye pain, visual fatigue and other discomfort. These symptoms of constant eye irritation affect the patient's quality of life. At present, anterior segment optical coherence tomography can be used for clinical diagnosis, and the novel monoclonal antibody D2-40, as a marker of lymphatic endothelial cell dilatation, has high specificity in pathological diagnosis. Previous studies have not fully defined the pathogenesis of the disease, and treatment methods vary. Conventional treatment has resulted in varying degrees of damage to the conjunctiva in patients. In recent years, anti-vascular endothelial growth factor drugs have been reported to be effective in treating the disease with few complications. This article reviews the pathogenesis, diagnosis and treatment of this rare disease in order to gain a better understanding of conjunctival lymphangiectasia and provide more support for clinical diagnosis and treatment.

Acute lung injury （ALI） is a common clinical inflammatory respiratory emergency with high morbidity and mortality， for which there is no effective and safe therapeutic drug. Nuclear factor-κB （NF-κB）， as a classic inflammatory signaling pathway， can interact with upstream and downstream regulatory factors such as Toll-like receptor 4 （TLR4）， mitogen- activated protein kinase （MAPK）， nucleotide-binding domain leucine-rich repeat and pyrin domain-containing receptor 3 （NLRP3）， high mobility group box-1 protein 1 （HMGB1）， to jointly affect ALI. This review summarizes the latest research findings in recent years regarding the treatment of ALI through traditional Chinese medicine （TCM） interventions targeting NF-κB signaling pathways. It has been found that a variety of TCM monomers （danshensu methyl ester， salidroside total glycosides， berberine， Codonopsis pilosula polysaccharides， ursolic acid， chrysophanol， and polyphenols from longan seed kernels， etc.） and compound formulas （Resolving-dampness and defeating-toxins formula， Jinyin qingre oral liquid， Xuebijing injection， Combined treatment of lung and intestine， Huangqi baihe decoction， etc.） can modulate NF-κB signaling pathway， and can prevent and control ALI by inhibiting inflammation， improving oxidative stress， reducing apoptosis and modulating the intestinal flora in a multi-pathway manner.

[摘 要] 目的：探讨程序性死亡蛋白1（PD-1）抑制剂与恶性黑色素瘤患者癌性疲劳（CRF）之间的关系及其影响因素。方法：选取2019年4月至2024年4月期间在济南市人民医院接受治疗的100例恶性黑色素瘤患者作为研究对象，使用中文版Piper疲劳量表评估这些患者在接受首次PD-1抑制剂治疗前后3个月内的疲劳状况。结果：使用PD-1抑制剂前后的患者疲劳评分存在显著差异（P < 0.001）。单变量分析发现，性别、吸烟史、肿瘤位置以及使用的PD-1抑制剂类型对于疲劳程度没有明显影响（均P > 0.05），而与年龄、疾病分期、贫血状态、白细胞减少症、继发性甲状腺机能减退（甲减）、继发性肾上腺皮质醇功能减退（AI）、继发性促肾上腺皮质激素降低（P < 0.05或P < 0.01或P < 0.001）相关联。进一步的多变量回归分析揭示，继发性甲减、继发性AI、贫血、白细胞减低是导致此类患者出现严重CRF的关键独立风险因素（均P < 0.05）。结论: PD-1抑制剂的不良反应继发性甲减、继发性AI、贫血、白细胞减低是恶性黑色素瘤患者CRF的独立风险因素。

It is believed that dampness is a key pathological factor contributing to digestive dysfunction in chronic renal failure. Damp pathogens tend to be entangled with or transformed into other pathogenic factors， obstructing the flow of qi， disturbing the functions of the zang-fu organs， and impairing the spleen and stomach's transportation and transformation functions， ultimately leading to disease onset. Based on this understanding， the treatment principle emphasizes dispelling dampness， regulating qi， and harmonizing the five zang organs. For the syndrome of spleen and kidney qi deficiency with dampness， the self-formulated Buyuan Fengzang Decoction （补元封藏煎） is used to tonify the kidney， secure essence， strengthen the spleen， and eliminate dampness. For the syndrome of turbid dampness obstructing the lung and stomach， the self-formulated Sulian Xiexin Decoction （苏连泻心汤） is applied to open with acrid， descend with bitter， dry dampness， and discharge turbidity. For the syndrome of dampness stagnating and transforming into heat， with concurrent spleen deficiency and liver qi stagnation， the self-formulated Chailian Wendan Decoction （柴连温胆汤） is employed to soothe the liver， strengthen the spleen， and disperse the accumulation. For the syndrome of damp obstruction with qi stagnation and constrained yang， the self-formulated Caozhi Erchen Decoction （草知二陈汤） is used to resolve dampness， relieve constraint， raise yang， and promote the defensive qi.

Immune inflammatory response runs through the whole pathological process of liver injury， but its specific regulatory mechanism remains unclear. Recent studies have shown that the Notch signaling pathway plays an important role in liver injury by regulating macrophage polarization， activating neutrophil recruitment， and modulating the differentiation of regulatory immune cells. This article systematically reviews the molecular mechanisms of the Notch signaling pathway in mediating immune inflammatory response in liver injury， in order to provide new perspectives for clarifying the molecular mechanism of immune inflammatory damage in liver diseases， as well as a new reference for future research directions.

Hepatic encephalopathy （HE） is a common severe liver disease syndrome in clinical practice and is one of the critical and severe diseases in internal medicine， and more than half of liver failure patients diagnosed with overt HE have a survival time of less than 1 year. A comprehensive analysis of the complex pathogenesis of HE and the development of diagnosis and treatment regimens based on evidence-based medicine are of great importance for alleviating high medical resource consumption， high medical expenses， and high incidence and mortality rates in clinical practice. The latest studies have shown that the intestinal tract and the central nervous system can perform bidirectional continuous interaction and signal transmission and regulate the function of inflammation signals， molecules， cells， and organs， which is known as neuroimmune communication and is highly consistent with the main pathological features of HE. With a focus on the mechanism of neuroimmune communication in HE， this article reviews the association between inflammation signal transduction via the gut-brain axis and neurotransmitter regulation and its role in neuroimmune communication in HE， which provides new ideas for the clinical diagnosis and treatment of HE and the research and development of related drugs.

Objective:To investigate the pathway of self-disclosure to posttraumatic growth in patients after cervical cancer surgery, and to provide reference for improving the level of posttraumatic growth in patients.Methods:A convenient sampling method was used to investigate 300 patients with cervical cancer after surgery in Shandong Provincial Hospital Affiliated to Shandong First Medical University from June to November 2022 by using general data questionnaire, Distress Disclosure Index (DDI), Connor-Davidson Resilience Scale (CD-RISC), the Shortened Chinese Version of the Family Resilience Assessment Scale (FRAS-C) and the Posttraumatic Growth Inventory (PTGI) in a cross-section study.Results:A total of 290 valid questionnaires were collected, with an effective recovery rate of 96.7%. The patients were aged 23-70(48.13 ± 10.39) years. The scores of self-disclosure, resilience, family resilience and posttraumatic growth were (46.41 ± 9.82), (67.06 ± 14.63), (108.18 ± 11.06) and (58.24 ± 17.86) respectively. The results of pathway analysis showed that self-disclosure could not only directly predict posttraumatic growth, but also indirectly predict posttraumatic growth through the mediating role of resilience and family resilience, and the chain mediating role of resilience and family resilience, respectively. The direct effect of self-disclosure on posttraumatic growth was 0.236(95% CI 0.138-0.335), and the chain mediating effect of family resilience and resilience between self-disclosure and posttraumatic growth was 0.036(95% CI 0.018-0.060). Conclusions:Medical staff should not only consider the direct influence of self-disclosure on posttraumatic growth, but also pay attention to improve the resilience and family flexibility of patients after cervical cancer surgery, so as to promote their posttraumatic growth.

Objective To investigate the protective effects of Sulforaphane(SFN)against high glucose(HG)-induced human platelet apoptosis and elucidate the underlying mechanisms in vitro.Methods Purified platelets obtained from healthy individuals were pre-incubated with various concentrations of SFN(5,10,or 20 μmol/L)or a vehicle control(0.05%DMSO)for 40 minutes at 37℃.Subsequently,the platelets were stimulated with normal glucose(NG,5 mmol/L)or high glucose(HG,25 mmol/L)for an additional duration of 90 minutes.Flow cytometry was employed to assess platelet mitochondrial membrane potential depolarization(Δψm),exposure of phosphatidylserine(PS),and generation of total intraplatelet reactive oxygen species(ROS).Phosphorylation levels of PI3K and Akt were determined using Western blot.Results Compared to NG-treated human platelets,HG significantly induced depolarization of platelet Δψm and exposure of PS(P＜0.001).These effects of HG were markedly attenuated by various concentrations of SFN(P＜0.001).Mechanistically,SFN down-regulated the phosphorylation levels of PI3K(P＜0.01)and Akt(P＜0.05),which were increased by HG when compared to the vehicle control,and substantially reduced total intracellular ROS levels(P＜0.001).The inhibitory effects of SFN on HG-induced phosphorylation of PI3K and Akt,as well as its efficacy on total intracellular ROS generation,Δψm depolarization,and PS exposure in HG-stimulated human platelets were completely reversed by a specific agonist for PI3K,740 Y-P.Conclusions The current study demonstrates that SFN exerts a protective effect on platelet apoptosis induced by HG,potentially through the down-regulation of the PI3K/Akt-mediated pathway in human platelets in vitro.These findings suggest that SFN may hold promise for improving thrombosis in diabetes mellitus and related chronic metabolic diseases.

Objective:To apply deep neural networks to predict high-precision dose distribution in volume modulated arc therapy (VMAT) plans for non-small cell lung cancer (NSCLC) patients.Methods:This study developed a U-shaped network called MHA-resunet, which incorporated a large kernel dilated convolution module and a multi-head attention module. The model was trained from 151 VMAT plans of NSCLC patients. CT images, planning target volume (PTV) and organs at risk (OARs) were fed into the independent input channel. The dose distribution was taken as the output to train the model. The performance of this network was compared with that of several commonly used networks, and the networks′performance was evaluated based on the voxel-level mean absolute error (MAE) within the PTV and OARs, as well as the error in clinical dose-volume metrics.Results:The MAE between the dose distribution predicted by MHA-resunet network and the manually planned dose distribution within the PTV area was 1.51 Gy, and the D98 and D95 errors in the PTV area were both < 1 Gy. Compared with the other three commonly used networks, the dose error of the MHA-resunet was the smallest in the PTV area and in OARs except for the heart. Conclusions:The proposed MHA-resunet network improves the receptive field to learn the relative spatial relationship between the PTV area and the OARs, enabling accurate prediction of dose distribution in NSCLC patients undergoing VMAT radiotherapy.