The tumor microenvironment includes blood vessels， lymph， nerves， non-malignant cells， and their metabolites at and near the tumor lesion site， which interact with cancer cells and promote cancer progression. Rapid proliferation of cancer cells increases oxygen consumption， or abnormalities in the structure and function of blood vessels in solid tumors lead to a decrease in oxygen supply， forming a hypoxia microenvironment. The existence of a hypoxia microenvironment is a typical pathophysiological feature of locally advanced solid tumors， widely present in various types of human malignant tumors. Hypoxia microenvironment is a sign of tumor microenvironment and an important and complex system in the breast tumor microenvironment. Its formation and development are closely related to the growth of breast cancer， occupying an important position in the research and treatment of breast cancer. With its advantages of multiple pathways and multiple targets， the effective monomer and compound of traditional Chinese medicine can better regulate the hypoxia microenvironment of breast cancer， inhibit the proliferation， invasion， and metastasis of breast cancer cells in the hypoxia environment， induce apoptosis， reverse their drug resistance， intervene in the metabolic reprogramming of breast cancer cells in the hypoxia environment， and inhibit their angiogenesis， thereby improving the quality of life of patients to a certain extent and prolonging the survival cycle of patients. This paper first summarized and discussed the effects of hypoxia microenvironment on proliferation， invasion， metastasis， drug resistance， immune function， metabolic reprogramming， non-coding RNA， iron death， and autophagy of breast cancer cells， which affected the occurrence and development of breast cancer， and it elaborated the mechanism behind it. Then， the paper elucidated the regulatory effect and mechanism of targeting the hypoxia microenvironment based on the two modes of effective monomer and compound of traditional Chinese medicine， so as to analyze and extract the deficiencies and directions of traditional Chinese medicine in regulating the hypoxia microenvironment and provide a theoretical reference for the effective treatment of breast cancer.

In the field of dental aesthetics,digital aesthetic design plays a crucial role in helping dentists to predict treatment outcomes vis-ually,as well as in enhancing the consistency of knowledge and understanding of aesthetic goals between dentists and patients.It serves as the foundation for achieving ideal aesthetic effects.However,there is no clear standard for this digital process currently in China and abroad.Many dentists lack of systematic understanding of how to carry out digital aesthetic design for treatment.To establish standardized processes for dental aesthetic design and to improve the homogeneity of treatment outcomes,Chinese Society of Digital Dental Industry(CSD-DI)convened domestic experts in related field to compile this consensus.This article elaborates on the key aspects of digital aesthetic data collection,integration steps,and the digital aesthetic design process.It also formulates a decision tree for dental aesthetics at macro level and outlines corresponding workflows for various clinical scenarios,serving as a reference for clinicians.

Objectives:To explore the risk factors of major adverse cardiovascular events (MACEs) in immune checkpoint inhibitor (ICI) related myocarditis and establish a predictive model.Methods:This was a retrospective case-control study. Tumor patients diagnosed with ICI related myocarditis in the First Affiliated Hospital of Guangzhou Medical University from May 2019 to August 2023 were selected and divided into non-MACE group and MACE group based on whether MACE occurred. Clinical and imaging data of the two groups were collected. Univariate and multivariate logistic regression models were used to analyze the risk factors for MACE in patients with ICI related myocarditis. According to the results of multivariate logistic regression analysis, R 4.1.0 software was used to construct the MACE risk prediction model for these patients and draw a nomogram. The receiver operating characteristic curve was used to evaluate the prediction ability of the prediction model.Results:A total of 35 patients with ICI related myocarditis, aged (63.9±8.2) years, were included, including 28 males (80%). There were 18 patients in the non-MACE group and 17 patients in the MACE group. Multivariate logistic regression analysis showed that elevated neutrophil to lymphocyte ratio ( OR=1.115, 95% CI 1.007-1.235, P=0.036) and ST-T segment changes ( OR=24.942, 95% CI 1.239-502.194, P=0.036) were risk factors for MACE in patients with ICI related myocarditis. The receiver operating characteristic curve indicated that the area under the curve of the prediction model was 0.967 (95% CI 0.916-1.000, P<0.001), with a sensitivity of 88.2% and specificity of 100%, demonstrating good predictive ability. Conclusion:Elevated neutrophil to lymphocyte ratio and ST-T segment change are independent risk factors for MACE in patients with ICI related myocarditis. Risk prediction model based on the above two indicators can assist in the early identification and individualized intervention of ICI related myocarditis patients.

Perioperative neurocognitive disorders(PND)is one of the common complications in the perioperative period,especially in elderly patients,and the incidence of PND is high and it is closely related to the prognosis of surgery.The currently accepted pathogenesis of PND includes central nervous sys-tem inflammation,synaptic dysfunction,apoptosis,oxidative stress,and neurofibrillary tangles,etc.Mi-croRNAs(miRNAs),as key gene expression regulators of neurological development and function,are not only directly involved in these processes,but also indirectly affect PND development through the modulation of the microbiota-gut-brain axis,perioperative mood regulation,and postoperative pain.In this paper,we review the role of miRNA in regulating perioperative neurocognitive disorders,with the aim of providing new ideas for the diagnosis and prevention of PND,as well as for the development of targeted therapies for this disease.

OBJECTIVE To predict the core ingredients, targets and signaling pathways of Sanhuang ointment in the treatment of haemorrhoids based on network pharmacology, and preliminarily discuss the mechanism of action preliminarily by means of molecular docking and experimental verification. METHODS Active ingredients, targets and haemorrhoid related targets of Sanhuang ointment were obtained through literature research and database screening. Association networks were constructed and core targets were screened by Cytoscape, and gene function analysis and pathway enrichment analysis were conducted. Autodock Vina was used for molecular docking verification, and the regulatory effects of Sanhuang ointment on core targets were verified by ELISA and immunohistochemistry. RESULTS The 77 active ingredients and 61 potential targets of Sanhuang ointment for treating haemorrhoids were collected. KEGG showed that Sanhuang ointment could regulate calcium signaling pathways, neuroactive ligand receptor interactions, cGMP-PKG pathway, etc. Affect 6 core targets of CGRP, NK-1R, TRPV1, VEGF, IL-6 and TNF-α. Molecular docking showed that Sanhuang ointment had a good affinity with target protein, and animal experiments verified that Sanhuang ointment could inhibit the expression of IL-6, CGRP, substance P, and promote the expression of VEGF. CONCLUSION Sanhuang ointment may act on CGRP, NK-1R and other targets, regulate Calcium signaling pathway and PI3K-Akt pathways, and exert analgesic and anti-inflammatory effects, promoting blood circulation and removing blood stasis to treat haemorrhoids.

Objective To analyze differential metabolites (DMs) in the urine of workers with occupational nickel exposure using non-targeted metabolomics, and to screen differential metabolic pathways. Methods A total of 30 nickel exposed workers were selected as the exposure group, and 30 administrative staff from the same factory were selected as the control group using the judgment sampling method. Urine samples of the individuals from the two groups were collected. The ultra-high performance liquid chromatography with quadrupole time-of-flight mass spectrometry and non-targeted metabolomics were used to detect and identify metabolites. The differential metabolic profiles were compared between workers of the two groups, and key differential metabolic pathways and potential biomarkers were screened. The association of DMs and urinary nickel level were evaluated by Spearman correlation coefficients. The sensitivity and specificity of biomarkers were assessed by receiver operating characteristic (ROC) curve analysis. Results A total of 418 metabolites were identified in the urine of worker in the exposure and control groups. The result of principal component analysis and orthogonal partial least squares analysis showed that there were 128 DMs in the urine of workers in the exposure group compared with the control group. These DMs were mainly enriched in glutathione metabolism, carnitine synthesis, and amino acid and nucleotide metabolism pathways, including glycine and serine metabolism. The result of correlation analysis and ROC curve analysis revealed that 4-methylcatechol, 4-vinylphenol sulfate, 2-hydroxyphenylacetone sulfate, 2-dodecylbenzenesulfonic acid, and decylbenzenesulfonic acid could be the potential biomarkers for nickel exposure (all area under the ROC curve >0.800). Conclusion There were significant differences in the urinary metabolic profiles of workers with occupational nickel exposure. The five DMs including 4-methylcatechol, 4-vinylphenol sulfate, 2-hydroxyphenylacetone sulfate, 2-dodecylbenzenesulfonic acid, and decylbenzenesulfonic acid. These DMs could be potential biomarkers of occupational nickel exposure.

This study presents a case of a girl of three year and 4 month old with ataxia and severe sen-sorineural hearing loss for 2 years.In order to improve hearing,she was hospitalized in the PUMC Hospital.Ge-netic testing performed found compound heterozygous variants of c.1186C＞T(p.P396S)and c.1357C＞T(p.R453W)in TWNK gene.After a multidisciplinary discussion of the case,the team suspected mitochondrial DNA depletion syndrome type 7(hepatocerebral type).The patient has shown nervous system impairment in-volvement but no evidence of liver dysfunction.The efficacy of cochlear implantation is uncertain and general anesthesia if applied will accelerate the progress of encephalopathy and might lead to multiple organ failure.Unsure of the perioperative safety,the parents of the girl did not chose the option of hearing intervention tempo-rarily,but chose oral symptomatic supportive treatment with coenzyme Q10,folate,levocarnitine,and complex vitamins as recommended.

Objective:To conduct a nationwide physician survey to better understand clinicians’ disease awareness, treatment patterns, and experience of Waldenstr?m macroglobulinemia (WM) in China.Methods:This cross-sectional study was conducted from February 2022 to July 2022 by recruiting clinicians with WM treatment experience from hematology, hematology-oncology, and oncology departments throughout China. Quantitative surveys were designed based on the qualitative interviews.Results:The study included 415 clinicians from 219 hospitals spread across thirty-three cities and twenty-two provinces. As for diagnosis, the laboratory tests prescribed by physicians for suspected WM patients were relatively consistent (92% -99% recommendation for laboratory, 79% -95% recommendation for pathology, 96% recommendation for gene testing, and 63% -83% recommendation for imaging examination). However, from a physician's perspective, there was 22% misdiagnosis occurred in clinical practice. The rate of misdiagnosis was higher in lower-level hospitals than in tertiary grade A hospitals (29% vs 21%, P<0.001). The main reasons for misdiagnosis were that WM was easily confused with other diseases, and physicians lacked the necessary knowledge to make an accurate diagnosis. In terms of gene testing in clinical practice, 96% of participating physicians believed that WM patients would require gene testing for MYD88 and CXCR4 mutations because the results of gene testing would aid in confirming diagnosis and treatment options. In terms of treatment, 55% of physicians thought that the most important goal was to achieve remission, while 54% and 51% of physicians wanted to improve laboratory and/or examination results and extend overall survival time, respectively. Among patients with treatment indications, physicians estimated that approximately 21% of them refused to receive treatment, mainly owing to a lack of affordable care and disease awareness. When selecting the most appropriate treatment regimens, physicians would consider patient affordability (63% ), comorbidity (61% ), and risk level (54% ). Regimens containing Bruton tyrosine kinase inhibitor (BTKi) were most widely recommended for both treatment-na?ve and relapsed/refractory patients (94% for all patients, 95% for treatment-na?ve patients, and 75% for relapsed/refractory patients), and most physicians recommended Ibrutinib (84% ). For those patients who received treatment, physicians reported that approximately 23% of patients did not comply with the treatment regimen due to a lack of affordability and disease awareness. Furthermore, 66% of physicians believe that in the future, increasing disease awareness and improving diagnosis rates is critical. Conclusions:This study is the first national physician survey of WM conducted in China. It systematically describes the issues that exist in WM diagnosis and treatment in China, such as a high rate of misdiagnosis, limited access to gene testing and new drugs, and poor patient adherence to treatment. Chinese doctors believe that improving doctors’ and patients’ understanding of WM is one of the most urgent issues that must be addressed right now.

Objective:To explore the efficacy and safety of ibrutinib for the treatment of newly treated and relapsed refractory (R/R) lymphoplasmacytic lymphoma (LPL) /Waldenstr?m macroglobulinemia (WM) .Methods:Retrospectively collected clinical data of 98 cases of newly treated and R/R LPL/WM patients who received ibrutinib treatment at the Hematology & Blood Diseases Hospital of the Chinese Academy of Medical Sciences from March 2016 to June 2023, and analyzed their efficacy and safety.Results:A total of 98 LPL/WM patients were included, which consisted of 45 newly treated patients and 53 R/R patients. Of these, 74 were males (75.5%) and the cohort had a median age of 64 (42-87) years. Eighty-eight patients were eligible for efficacy evaluation with a median treatment time of 20.8 (2.1-55.0) months, a major remission rate (MRR) of 78.4%, and an overall response rate (ORR) of 85.2%. The MRR and ORR of the newly treated patients were 78.4% and 86.5%, respectively, whereas the MRR and ORR of the R/R patients were 78.4% and 84.3%, respectively. There were no statistically significant differences in MRR and ORR between the initial treatment and R/R patients (all P values >0.05) . The median follow-up period was 29.1 (2.9-50.3) months and the median overall survival time for newly treated and R/R patients was not reached. The median progression-free survival time was 23.5 (95% CI 10.5-36.5) months and 45.0 (95% CI 34.0-56.0) months, respectively, with no statistically significant differences (all P values >0.05) . There were 25 deceased patients and no deaths were related to ibrutinib treatment. The main adverse reactions of ibrutinib were thrombocytopenia (5.1%) , pneumonia (8.1%) , and hyperuricemia (21.4%) . The incidence of atrial fibrillation was 2.0%. Conclusion:Ibrutinib exhibits good efficacy and safety for newly treated and R/R LPL/WM patients.

Rapid and accurate diagnostic technologies are crucial for early detection and diagnosis of diseases. Electrowetting-on-dielectric digital microfluidics, with its high-precision detection and high-throughput screening capabilities, significantly enhances the accuracy and efficiency in early disease diagnosis and personalized treatment, enabling swift disease detection and widespread screening. This article provides a comprehensive review of the working principles and fabrication processes of digital microfluidic chips based on electrowetting on dielectric method. It details the latest research progress in the areas of nucleic acids, proteins, and cells, organizes the commercialization of digital microfluidics technology, and finally discusses the current challenges and future directions of digital microfluidic chips.