Naringin is a flavonoid compound with a wide range of biological and pharmacologi-cal activities,which can be used in treating tumor,diabetes,neurodegenerative diseases,cardiovascu-lar diseases,metabolic syndrome,etc.Among them,the application of naringin in cardiovascular diseases has attracted the attention of many re-searchers.This article mainly reviews the role of naringin in cardiovascular disease(regulating blood lipids,anti atherosclerosis,lowering blood pres-sure,inhibiting myocardial hypertrophy,anti myo-cardial infarction,protecting myocardial ischemia/reperfusion injury,reducing myocardial ischemia/reperfusion injury and improving pulmonary arteri-al hypertension),the protective effect on cardiotox-icity,and the signal pathways in cardiovascular dis-ease(PI3K-Akt-mTOR,p-eNOS/p-Akt/p-ERK,miR-126/GSK-3 β/β-Catenin),clinical trials,etc.This pa-per is expected to review the current research sta-tus of naringin in cells and animal models so as to reveal its clinical application prospects and provide reference for further research in related fields.

Objective:To explore genomic features associated with gemcitabine sensitivity, patient-derived organoid models of biliary tract cancer (BTC) were established and characterized.Methods:This is an experimental study. The tissue specimens of BTC were collected from patients who underwent surgical resection at the Department of Hepatobiliary and Pancreatic Surgery,the Second Affiliated Hospital of Zhejiang University School of Medicine between January 2020 and December 2023. The tumor organoids were cultured in vitro and histologically characterized. Drug sensitivity testing was performed using gemcitabine,cisplatin,paclitaxel,fluorouracil,and lenvatinib etc. to evaluate cell viability. The correlation between the drug sensitivity of organoids and clinical therapeutic response was analyzed.Results:Thirty-eight patient-derived organoids (PDO) models were successfully established from 43 biliary tract malignancy patients with complete follow-up data,including gallbladder cancer PDO 14 cases,distal bile duct cancer PDO 16 cases,intrahepatic cholangiocarcinoma PDO 8 cases,achieving an overall success rate of 88.4%. Drug sensitivity testing (DST) was performed on the successfully generated PDO,with 35 models successfully completing DST experiments. The overall consistency rate between drug responses in PDOs and clinical survival outcomes in corresponding patients was 8/14. Transcriptomic analysis of gemcitabine-sensitive vs. gemcitabine-resistant PDO identified 71 differentially expressed genes in the resistant group,the significantly up-regulated genes including GLDC, LINC01595, IL-27, ANGPTL3, CYP7A1,and AKR1C1;the significantly down-regulated genes including P2RY2,LIPC,and ECHDC3. Conclusion:A biobank of patient-derived organoids of BTC has been established,which demonstrates its potential as preclinical models and tools for predicting chemotherapy responses for BTC patients.

Objective Under the guidance of Zhuang medicine theory,this study aims to investigate the medicinal and compatibility rules of authentic medicinal pearls.Method This article focuses on the fourth national survey of traditional Chinese medicine resources—general survey of marine traditional Chinese medicine resources in Guangxi,led by Professor Lin Jiang's team from Guangxi University of Traditional Chinese Medicine and Guangxi Famous Traditional Chinese Medicine.The survey collected original prescriptions containing pearls,as well as data recorded in Zhuang medicine monographs containing pearls.The study integrated the efficacy,indications,pharmacology,and clinical research of pearl Zhuang medicine.Under the guidance of Zhuang medicine prescription compatibility theory,Zhuang medicine disease classification,and Zhuang medicine classification theory,this study explores the compatibility rules based on the data and functions of Zhuang medicine pearl formula.Result Zhuang medicine pearls taste sweet and salty,with a cold nature;It has the effects of activating the Qiao wu(brain),regulating Long lu(blood circulatory system)and Huo lu(nervous system),clearing heat and toxins,calming the mind,calming palpitations,relieving cough,promoting muscle growth,nourishing yin fluids,and Clearing eye mistiness;Indications:Nian nao nuo(Insomnia),Hen feng(Infantile Convulsions),Long lei(Epilepsy),Fright Palpitations,A rou tian(Diabetes),Huo yan ma(Sore throat),Bei ding(Deep-Rooted Boil),Bei nong(Sores and Ulcers),Redness and visual obstruction due to corneal opacity,Re Nong(Otitis media),Kou chuang(Oral ulcers),Da ning(Swelling and pain of eye).Based on the analysis of data on the formula of Zhuang medicine pearls,it was found that the topical use of Zhuang medicine pearls is concentrated in diseases of the ENT(Ear,Nose,and Throat),Ophthalmology,and diseases of the skin and subcutaneous tissue.When combined with drugs such as regulating Long lu,clearing heat toxin,and eliminating dampness-toxin,it is used to treat diseases such as Redness and visual obstruction due to corneal opacity,Oral ulcers,and Skin ulcers;For internal use,it is often combined with medicines that regulating Long lu,replenishing qi and blood,eliminating dampness-toxin,and nourishing the heart-mind,used in hypertension and palpitations.When paired with the medicines of clearing heat toxin,replenishing qi and blood,regulating Qiaowu,it is used to treat insomnia and epilepsy.Based on the analysis of pearl function,it is used in combination with airway and detoxifying drugs to treat airway diseases;Combination therapy with regulating Long lu and Qiao wu(brain)medicine for the treatment of Long lu disease;Combination treatment of gynecological diseases with regulating Long lu and Huo lu medicine and Bu xu medicine;Combination therapy with heat-clearing,detoxifying,and swelling-reducing medicines or astringents,for the treatment of persistent non-healing sores and ulcers;Used in combination with antipyretic drugs and yin tonifying drugs to treat ophthalmic diseases.Conclusion Zhuang medicine pearl has a wide range of therapeutic effects,and its efficacy can be enhanced by compatibility with different Zhuang medicines.Future research can combine modern compatibility methods of traditional Chinese medicine to optimize the compatibility scheme of pearls,study the specialized disease and prescription of Zhuang medicine pearls,combine Zhuang medicine with Western medicine to form prescriptions,and combine the pharmacological effects of pearls to form prescriptions.In depth exploration of the pharmacological substance basis and mechanism of action of pearl prescriptions can be conducted to develop new Zhuang medicine preparations for pearls.

Naringin is a flavonoid compound with a wide range of biological and pharmacologi-cal activities,which can be used in treating tumor,diabetes,neurodegenerative diseases,cardiovascu-lar diseases,metabolic syndrome,etc.Among them,the application of naringin in cardiovascular diseases has attracted the attention of many re-searchers.This article mainly reviews the role of naringin in cardiovascular disease(regulating blood lipids,anti atherosclerosis,lowering blood pres-sure,inhibiting myocardial hypertrophy,anti myo-cardial infarction,protecting myocardial ischemia/reperfusion injury,reducing myocardial ischemia/reperfusion injury and improving pulmonary arteri-al hypertension),the protective effect on cardiotox-icity,and the signal pathways in cardiovascular dis-ease(PI3K-Akt-mTOR,p-eNOS/p-Akt/p-ERK,miR-126/GSK-3 β/β-Catenin),clinical trials,etc.This pa-per is expected to review the current research sta-tus of naringin in cells and animal models so as to reveal its clinical application prospects and provide reference for further research in related fields.

Objective Under the guidance of Zhuang medicine theory,this study aims to investigate the medicinal and compatibility rules of authentic medicinal pearls.Method This article focuses on the fourth national survey of traditional Chinese medicine resources—general survey of marine traditional Chinese medicine resources in Guangxi,led by Professor Lin Jiang's team from Guangxi University of Traditional Chinese Medicine and Guangxi Famous Traditional Chinese Medicine.The survey collected original prescriptions containing pearls,as well as data recorded in Zhuang medicine monographs containing pearls.The study integrated the efficacy,indications,pharmacology,and clinical research of pearl Zhuang medicine.Under the guidance of Zhuang medicine prescription compatibility theory,Zhuang medicine disease classification,and Zhuang medicine classification theory,this study explores the compatibility rules based on the data and functions of Zhuang medicine pearl formula.Result Zhuang medicine pearls taste sweet and salty,with a cold nature;It has the effects of activating the Qiao wu(brain),regulating Long lu(blood circulatory system)and Huo lu(nervous system),clearing heat and toxins,calming the mind,calming palpitations,relieving cough,promoting muscle growth,nourishing yin fluids,and Clearing eye mistiness;Indications:Nian nao nuo(Insomnia),Hen feng(Infantile Convulsions),Long lei(Epilepsy),Fright Palpitations,A rou tian(Diabetes),Huo yan ma(Sore throat),Bei ding(Deep-Rooted Boil),Bei nong(Sores and Ulcers),Redness and visual obstruction due to corneal opacity,Re Nong(Otitis media),Kou chuang(Oral ulcers),Da ning(Swelling and pain of eye).Based on the analysis of data on the formula of Zhuang medicine pearls,it was found that the topical use of Zhuang medicine pearls is concentrated in diseases of the ENT(Ear,Nose,and Throat),Ophthalmology,and diseases of the skin and subcutaneous tissue.When combined with drugs such as regulating Long lu,clearing heat toxin,and eliminating dampness-toxin,it is used to treat diseases such as Redness and visual obstruction due to corneal opacity,Oral ulcers,and Skin ulcers;For internal use,it is often combined with medicines that regulating Long lu,replenishing qi and blood,eliminating dampness-toxin,and nourishing the heart-mind,used in hypertension and palpitations.When paired with the medicines of clearing heat toxin,replenishing qi and blood,regulating Qiaowu,it is used to treat insomnia and epilepsy.Based on the analysis of pearl function,it is used in combination with airway and detoxifying drugs to treat airway diseases;Combination therapy with regulating Long lu and Qiao wu(brain)medicine for the treatment of Long lu disease;Combination treatment of gynecological diseases with regulating Long lu and Huo lu medicine and Bu xu medicine;Combination therapy with heat-clearing,detoxifying,and swelling-reducing medicines or astringents,for the treatment of persistent non-healing sores and ulcers;Used in combination with antipyretic drugs and yin tonifying drugs to treat ophthalmic diseases.Conclusion Zhuang medicine pearl has a wide range of therapeutic effects,and its efficacy can be enhanced by compatibility with different Zhuang medicines.Future research can combine modern compatibility methods of traditional Chinese medicine to optimize the compatibility scheme of pearls,study the specialized disease and prescription of Zhuang medicine pearls,combine Zhuang medicine with Western medicine to form prescriptions,and combine the pharmacological effects of pearls to form prescriptions.In depth exploration of the pharmacological substance basis and mechanism of action of pearl prescriptions can be conducted to develop new Zhuang medicine preparations for pearls.

Objective:To explore genomic features associated with gemcitabine sensitivity, patient-derived organoid models of biliary tract cancer (BTC) were established and characterized.Methods:This is an experimental study. The tissue specimens of BTC were collected from patients who underwent surgical resection at the Department of Hepatobiliary and Pancreatic Surgery,the Second Affiliated Hospital of Zhejiang University School of Medicine between January 2020 and December 2023. The tumor organoids were cultured in vitro and histologically characterized. Drug sensitivity testing was performed using gemcitabine,cisplatin,paclitaxel,fluorouracil,and lenvatinib etc. to evaluate cell viability. The correlation between the drug sensitivity of organoids and clinical therapeutic response was analyzed.Results:Thirty-eight patient-derived organoids (PDO) models were successfully established from 43 biliary tract malignancy patients with complete follow-up data,including gallbladder cancer PDO 14 cases,distal bile duct cancer PDO 16 cases,intrahepatic cholangiocarcinoma PDO 8 cases,achieving an overall success rate of 88.4%. Drug sensitivity testing (DST) was performed on the successfully generated PDO,with 35 models successfully completing DST experiments. The overall consistency rate between drug responses in PDOs and clinical survival outcomes in corresponding patients was 8/14. Transcriptomic analysis of gemcitabine-sensitive vs. gemcitabine-resistant PDO identified 71 differentially expressed genes in the resistant group,the significantly up-regulated genes including GLDC, LINC01595, IL-27, ANGPTL3, CYP7A1,and AKR1C1;the significantly down-regulated genes including P2RY2,LIPC,and ECHDC3. Conclusion:A biobank of patient-derived organoids of BTC has been established,which demonstrates its potential as preclinical models and tools for predicting chemotherapy responses for BTC patients.

With the increasing proportion of human papilloma virus(HPV)infection in the pathogenic factors of oro-pharyngeal cancer,a series of changes have occurred in the surgical treatment.While the treatment mode has been im-proved,there are still many problems,including the inconsistency between diagnosis and treatment modes,the lack of popularization of reconstruction technology,the imperfect post-treatment rehabilitation system,and the lack of effective preventive measures.Especially in terms of treatment mode for early oropharyngeal cancer,there is no unified conclu-sion whether it is surgery alone or radiotherapy alone,and whether robotic minimally invasive surgery has better func-tional protection than radiotherapy.For advanced oropharyngeal cancer,there is greater controversy over the treatment mode.It is still unclear whether to adopt a non-surgical treatment mode of synchronous chemoradiotherapy or induction chemotherapy combined with synchronous chemoradiotherapy,or a treatment mode of surgery combined with postopera-tive chemoradiotherapy.In order to standardize the surgical treatment of oropharyngeal cancer in China and clarify the indications for surgical treatment of oropharyngeal cancer,this expert consensus,based on the characteristics and treat-ment status of oropharyngeal cancer in China and combined with the international latest theories and practices,forms consensus opinions in multiple aspects of preoperative evaluation,surgical indication determination,primary tumor re-section,neck lymph node dissection,postoperative defect repair,postoperative complication management prognosis and follow-up of oropharyngeal cancer patients.The key points include:① Before the treatment of oropharyngeal cancer,the expression of P16 protein should be detected to clarify HPV status;② Perform enhanced magnetic resonance imaging of the maxillofacial region before surgery to evaluate the invasion of oropharyngeal cancer and guide precise surgical resec-tion of oropharyngeal cancer.Evaluating mouth opening and airway status is crucial for surgical approach decisions and postoperative risk prediction;③ For oropharyngeal cancer patients who have to undergo major surgery and cannot eat for one to two months,it is recommended to undergo percutaneous endoscopic gastrostomy before surgery to effectively improve their nutritional intake during treatment;④ Early-stage oropharyngeal cancer patients may opt for either sur-gery alone or radiation therapy alone.For intermediate and advanced stages,HPV-related oropharyngeal cancer general-ly prioritizes radiation therapy,with concurrent chemotherapy considered based on tumor staging.Surgical treatment is recommended as the first choice for HPV unrelated oropharyngeal squamous cell carcinoma(including primary and re-current)and recurrent HPV related oropharyngeal squamous cell carcinoma after radiotherapy and chemotherapy;⑤ For primary exogenous T1-2 oropharyngeal cancer,direct surgery through the oral approach or da Vinci robotic sur-gery is preferred.For T3-4 patients with advanced oropharyngeal cancer,it is recommended to use temporary mandibu-lectomy approach and lateral pharyngotomy approach for surgery as appropriate;⑥ For cT1-2N0 oropharyngeal cancer patients with tumor invasion depth＞3 mm and cT3-4N0 HPV unrelated oropharyngeal cancer patients,selective neck dissection of levels ⅠB to Ⅳ is recommended.For cN+HPV unrelated oropharyngeal cancer patients,therapeutic neck dissection in regions Ⅰ-Ⅴ is advised;⑦ If PET-CT scan at 12 or more weeks after completion of radiation shows intense FDG uptake in any node,or imaging suggests continuous enlargement of lymph nodes,the patient should undergo neck dissection;⑧ For patients with suspected extracapsular invasion preoperatively,lymph node dissection should include removal of surrounding muscle and adipose connective tissue;⑨ The reconstruction of oropharyngeal cancer defects should follow the principle of reconstruction steps,with priority given to adjacent flaps,followed by distal pedicled flaps,and finally free flaps.The anterolateral thigh flap with abundant tissue can be used as the preferred flap for large-scale postoperative defects.

Although the understanding of sepsis has evolved from "sepsis 1.0" to "sepsis 3.0", and the consensus on clinical management of sepsis has been continuously updated, the incidence rate and mortality of sepsis remain high. Therefore, in-depth investigation of the pathogenesis and related influencing factors of sepsis is of great significance for revealing the nature of sepsis and improving the clinical outcome of sepsis patients. This review will focus on the key issues in the basic research of sepsis, and summarize the recent advances and challenges in this field, mainly including genetic polymorphism, microorganisms, high-mobility group box 1 (HMGB1), endothelial dysfunction, immunotherapy, and biomarkers, aiming to provide new insights for the diagnosis and treatment of sepsis.

Sepsis-related organ dysfunction is associated with increased morbidity and mortality. Previous studies have found that the endothelium plays crucial roles in maintaining the vascular permeability during sepsis, as well as in regulating inflammation and thrombosis. During sepsis, endothelial cells may release cytokines, chemokines, and pro-coagulant factors, as well as express adhesion molecules. In general, endothelial responses during sepsis typically inhibit bacterial transmission and coordinate leukocyte recruitment to promote bacterial clearance. However, excessive or prolonged endothelial activation can lead to impaired microcirculation, tissue hypoperfusion, and organ dysfunction. Given the structural and functional heterogeneity of endothelial cells in different organs, there are potential differences in endothelial responses by organ type, and the risk of organ damage may vary accordingly. This article reviews the endothelial response observed in sepsis and its effects on organ function, summarizes current progress in the development of therapeutic interventions targeting the endothelial response, and discusses future research directions to serve as a reference for researchers in the field.
Sepsis/complications* ; Humans ; Multiple Organ Failure/etiology* ; Endothelium, Vascular/physiopathology* ; Endothelial Cells/metabolism* ; Cytokines/metabolism* ; Animals

BACKGROUND: Islet transplantation is currently considered the most promising method for treating insulin-dependent diabetes. The two most-studied artificial islets are alginate-encapsulated b cells or b cell spheroids. As three-dimensional (3D) models, both artificial islets have better insulin secretory functions and transplantation efficiencies than cells in twodimensional (2D) monolayer culture. However, the effects of these two methods have not been compared yet. Therefore, in this study, cells from the mouse islet b cell line Min6 were constructed as scaffold-free spheroids or alginate-encapsulated dispersed cells. METHODS: MIN6 cell spheroids were prepared by using Agarose-base microwell arrays. The insulin secretion level was determined by mouse insulin ELISA kit, and the gene and protein expression status of the MIN6 were performed by Quantitative polymerase chain reaction and immunoblot, respectively. RESULTS: Both 3D cultures effectively promoted the proliferation and glucose-stimulated insulin release (GSIS) of MIN6 cells compared to 2D adherent cells. Furthermore, 1% alginate-encapsulated MIN6 cells demonstrated more significant effects than the spheroids. In general, three pancreatic genes were expressed at higher levels in response to the 3D culture than to the 2D culture, and pancreatic/duodenal homeobox-1 (PDX1) expression was higher in the cells encapsulated in 1% alginate than that in the spheroids. A western blot analysis showed that 1% alginate-encapsulated MIN6 cells activated the phosphoinositide 3-kinase (PI3K)/serine/threonine protein kinase (AKT)/forkhead transcription factor FKHR (FoxO1) pathway more than the spheroids, 0.5% alginate-, or 2% alginate-encapsulated cells did. The 3D MIN6 culture, therefore, showed improved effects compared to the 2D culture, and the 1% alginate-encapsulated MIN6 cells exhibited better effects than the spheroids. The upregulation of PDX1 expression through the activation of the PI3K/AKT/FoxO1 pathway may mediate the improved cell proliferation and GSIS in 1% alginate-encapsulated MIN6 cells. CONCLUSION This study may contribute to the construction of in vitro culture systems for pancreatic islets to meet clinical requirements.