Lonicerae Japonicae Flos refers to the dried flower buds or flowers about to open of Lonicera japonica （Caprifoliaceae）. Its dried flower buds or early blooming flowers are listed in the Pharmacopoeia of the People's Republic of China （2020 edition） as official medicinal materials. As a Chinese medicine with "heat-clearing and detoxifying" properties and a classic medicinal-edible resource， it is mainly produced in northern authentic producing regions such as Shandong， Henan， and Hebei in China. Lonicerae Japonicae Flos contains abundant bioactive substances that are considered safe and effective， with functions including relieving sore throat， antibacterial and anti-inflammatory effects， and immune regulation. In recent years， with the modernization of traditional Chinese medicine （TCM） and the rapid development of the "big health" industry， Lonicerae Japonicae Flos has become a research hotspot in the fields of natural medicines and functional foods due to its multi-target pharmacological activities and broad application potential. To date， chemical constituents identified from Lonicerae Japonicae Flos include organic acids， flavonoids， iridoids， triterpenes， triterpenoid saponins， and volatile oils. Modern pharmacological studies have shown that Lonicerae Japonicae Flos possesses anti-inflammatory， antibacterial， antioxidant， antiviral， antidiabetic， cardiovascular and neuroprotective， and immunomodulatory activities. In terms of modern applications， Lonicerae Japonicae Flos has developed into a full industrial chain covering pharmaceuticals， health products， daily chemical products， and food additives， demonstrating high medicinal and health value. Strengthening the development of Lonicerae Japonicae Flos-based health products is of great significance. Based on relevant domestic and international literature， this paper systematically reviews the innovative applications of Lonicerae Japonicae Flos in traditional medicine， modern clinical formulations， health foods， and daily chemical products from the perspectives of chemical composition， pharmacological effects， and modern applications， aiming to further deepen basic research on Lonicerae Japonicae Flos. Meanwhile， this paper analyzes and proposes suggestions for promoting applied research on Lonicerae Japonicae Flos， in order to provide a scientific basis for its sound development and to offer references for the rational development and comprehensive utilization of medicinal and edible resources.

BACKGROUND:Studies have shown that ischemia-induced cellular autophagy dysfunction is a key factor in brain injury.Autophagy related genes 6(ATG6),microtubule-associated protein 1 light chain(LC3),p62,and other autophagy key proteins are involved in the processes such as neuronal axonal degeneration,death,and intracellular homeostasis maintenance,playing an important role in the recovery of neural function. OBJECTIVE:To review the research progress in the role of cellular autophagy in cerebral ischemic injury and the regulatory mechanism of traditional Chinese medicine. METHODS:The first author used"ischemic stroke,brain tissue injury,cellular autophagy,signaling pathways,traditional Chinese medicine compounds,terpenoids,alkaloids,flavonoids,saponins,lignans,phthalates"as Chinese and English keywords respectively to search for literature on autophagy,cerebral ischemic injury,and the regulatory mechanisms of traditional Chinese medicine from China National Knowledge Infrastructure(CNKI)and PubMed databases from January 2016 to February 2024.Literature that is not highly relevant,repetitive,or outdated was excluded.A total of 1 746 relevant literature were retrieved,and 92 articles were ultimately included. RESULTS AND CONCLUSION:Numerous studies have confirmed that autophagy plays an important role in cerebral ischemic injury.Moderate autophagy can promote cell survival,while excessive autophagy exacerbates brain injury.Traditional Chinese medicine can regulate the expression of autophagy related proteins,inhibit neuronal necrosis and apoptosis,and exert neuroprotective effects at different stages of cerebral ischemia by regulating signaling pathways such as PI3K/Akt/mTOR,AMPK-mTOR,and mitogen activated protein kinase.

Edema， as a common pathological phenomenon， is essentially the abnormal accumulation of body fluids in the interstitial spaces of human tissues and is often a direct manifestation of various underlying diseases， such as heart failure， impaired renal filtration function， or liver metabolic disorders. In the Western medical system， strategies for treating edema primarily focus on the use of diuretics to promote the excretion of excess fluid in the body， while simultaneously addressing the underlying causes through targeted treatment. However， long-term reliance on the use of diuretics may lead to a decrease in drug sensitivity and induce side effects， including electrolyte disorders such as hypokalemia and hypercalcemia， posing a potential threat to patients' overall health. Compared with Western medicine， traditional Chinese medicine （TCM） has demonstrated well-recognized and sustained efficacy in treating edema with its unique theoretical system. Zhulingtang， as a classic and commonly used TCM formula， is widely applied as it can effectively relieve edema and related symptoms. In recent years， ongoing in-depth studies on the treatment of edema with Zhulingtang have revealed multiple mechanisms of action of Zhulingtang， including the regulation of water metabolism and the reduction of inflammatory responses， thereby providing a solid theoretical basis for clinical practice. This review summarized the research progress on the treatment of edema with Zhulingtang in recent years and analyzed the active ingredients and action pathways of Zhulingtang. Additionally， the primary mechanisms of action and efficacy were systematically analyzed， so as to provide references for the clinical application of Zhulingtang in treating various types of edema， such as cardiogenic edema， renal edema， and hepatogenic edema. This review aims to offer theoretical support and practical guidance for clinicians in deciding treatment approaches， as well as references for subsequent in-depth studies， thereby promoting further development of TCM in the treatment of edema.

Edema， as a common pathological phenomenon， is essentially the abnormal accumulation of body fluids in the interstitial spaces of human tissues and is often a direct manifestation of various underlying diseases， such as heart failure， impaired renal filtration function， or liver metabolic disorders. In the Western medical system， strategies for treating edema primarily focus on the use of diuretics to promote the excretion of excess fluid in the body， while simultaneously addressing the underlying causes through targeted treatment. However， long-term reliance on the use of diuretics may lead to a decrease in drug sensitivity and induce side effects， including electrolyte disorders such as hypokalemia and hypercalcemia， posing a potential threat to patients' overall health. Compared with Western medicine， traditional Chinese medicine （TCM） has demonstrated well-recognized and sustained efficacy in treating edema with its unique theoretical system. Zhulingtang， as a classic and commonly used TCM formula， is widely applied as it can effectively relieve edema and related symptoms. In recent years， ongoing in-depth studies on the treatment of edema with Zhulingtang have revealed multiple mechanisms of action of Zhulingtang， including the regulation of water metabolism and the reduction of inflammatory responses， thereby providing a solid theoretical basis for clinical practice. This review summarized the research progress on the treatment of edema with Zhulingtang in recent years and analyzed the active ingredients and action pathways of Zhulingtang. Additionally， the primary mechanisms of action and efficacy were systematically analyzed， so as to provide references for the clinical application of Zhulingtang in treating various types of edema， such as cardiogenic edema， renal edema， and hepatogenic edema. This review aims to offer theoretical support and practical guidance for clinicians in deciding treatment approaches， as well as references for subsequent in-depth studies， thereby promoting further development of TCM in the treatment of edema.

BACKGROUND:Ferroptosis is a programmed cell death mode regulated by iron dependent lipid peroxidation,closely related to the occurrence,development,and outcome of ischemic brain injury.With the continuous deepening of research on ferroptosis in recent years,it has been found that Chinese herbal compounds and monomers can regulate ferroptosis by reducing iron overload,reducing the production of reactive oxygen species,and regulating lipid synthesis,to alleviate cerebral ischemic injury and promote neurological function recovery.OBJECTIVE:To explore the relationship between ferroptosis and ischemic brain injury,and the mechanism by which traditional Chinese medicine regulates ferroptosis in the treatment of ischemic brain injury.METHODS:Literature on ferroptosis and ischemic brain injury and the regulatory mechanism of traditional Chinese medicine published from January 2018 to May 2024 was searched in CNKI and PubMed databases.The search terms were"iron death,ischemic stroke,brain injury,reactive oxygen species,lipid metabolism,traditional Chinese medicine formulas,terpenes,flavonoids,phenols,alkaloids,phthalides"in Chinese and English,respectively.Irrelevant,duplicated or outdated literature was excluded.A total of 1 526 relevant literature were retrieved,and 87 articles were ultimately included.RESULTS AND CONCLUSION:Numerous experimental studies have confirmed that ferroptosis plays an important role in ischemic brain injury.Chinese medicine prescriptions can regulate ferroptosis through various approaches,for examples:total saponins of Panax notoginseng can regulate iron metabolism and inhibit lipid peroxidation;carvacrol inhibits neuronal ferroptosis by increasing glutathione peroxidase 4 expression;Chinese herbal compounds and monomeric active ingredients can regulate ferroptosis-related pathways,such as glutathione/glutathione peroxidase 4(GPX4),nuclear factor E2-related factor 2(Nrf2)/hemoglobin oxygenase 1(HO-1),ferric death inhibitory protein 1(FSP1)/CoQ10 and guanosine triphosphate cyclohydrolase 1(GCH1)/tetrahydrobiopterin(BH4),to reduce neuronal damage and death,and exert neuroprotective effects.

Mitochondrial autophagy is an important mechanism for maintaining cellular homeostasis,closely related to the occurrence and development of cerebral ischemic injury,and is an important way of neuronal death.In recent years,a large number of experimental studies have confirmed that traditional Chinese medicine has a significant effect on treating cerebral ischemic injury.Its advantages of multi-target,multi pathway,low toxicity and high efficiency have become an important component of the treatment of cerebral ischemic injury.Traditional Chinese medicine formulas and monomeric active ingredients such as Xiaoxuming decoction,Zishen Huoxue formula,flavonoids,alkaloids,etc.can regulate mitochondrial autophagy related signaling pathways and targets,inhibit neuronal autophagic death,alleviate pathological damage to brain tissue,and exert neuroprotective effects.This article analyzes the molecular mechanism of traditional Chinese medicine regulating mitochondrial autophagy in the treatment of cerebral ischemic injury from four aspects:an overview of mitochondrial autophagy,related signaling pathways,its relationship with cerebral ischemic injury,and the regulatory effects of traditional Chinese medicine.The aim is to provide ideas and references for future basic research and clinical treatment.

BACKGROUND:Ferroptosis is a programmed cell death mode regulated by iron dependent lipid peroxidation,closely related to the occurrence,development,and outcome of ischemic brain injury.With the continuous deepening of research on ferroptosis in recent years,it has been found that Chinese herbal compounds and monomers can regulate ferroptosis by reducing iron overload,reducing the production of reactive oxygen species,and regulating lipid synthesis,to alleviate cerebral ischemic injury and promote neurological function recovery.OBJECTIVE:To explore the relationship between ferroptosis and ischemic brain injury,and the mechanism by which traditional Chinese medicine regulates ferroptosis in the treatment of ischemic brain injury.METHODS:Literature on ferroptosis and ischemic brain injury and the regulatory mechanism of traditional Chinese medicine published from January 2018 to May 2024 was searched in CNKI and PubMed databases.The search terms were"iron death,ischemic stroke,brain injury,reactive oxygen species,lipid metabolism,traditional Chinese medicine formulas,terpenes,flavonoids,phenols,alkaloids,phthalides"in Chinese and English,respectively.Irrelevant,duplicated or outdated literature was excluded.A total of 1 526 relevant literature were retrieved,and 87 articles were ultimately included.RESULTS AND CONCLUSION:Numerous experimental studies have confirmed that ferroptosis plays an important role in ischemic brain injury.Chinese medicine prescriptions can regulate ferroptosis through various approaches,for examples:total saponins of Panax notoginseng can regulate iron metabolism and inhibit lipid peroxidation;carvacrol inhibits neuronal ferroptosis by increasing glutathione peroxidase 4 expression;Chinese herbal compounds and monomeric active ingredients can regulate ferroptosis-related pathways,such as glutathione/glutathione peroxidase 4(GPX4),nuclear factor E2-related factor 2(Nrf2)/hemoglobin oxygenase 1(HO-1),ferric death inhibitory protein 1(FSP1)/CoQ10 and guanosine triphosphate cyclohydrolase 1(GCH1)/tetrahydrobiopterin(BH4),to reduce neuronal damage and death,and exert neuroprotective effects.

Mitochondrial autophagy is an important mechanism for maintaining cellular homeostasis,closely related to the occurrence and development of cerebral ischemic injury,and is an important way of neuronal death.In recent years,a large number of experimental studies have confirmed that traditional Chinese medicine has a significant effect on treating cerebral ischemic injury.Its advantages of multi-target,multi pathway,low toxicity and high efficiency have become an important component of the treatment of cerebral ischemic injury.Traditional Chinese medicine formulas and monomeric active ingredients such as Xiaoxuming decoction,Zishen Huoxue formula,flavonoids,alkaloids,etc.can regulate mitochondrial autophagy related signaling pathways and targets,inhibit neuronal autophagic death,alleviate pathological damage to brain tissue,and exert neuroprotective effects.This article analyzes the molecular mechanism of traditional Chinese medicine regulating mitochondrial autophagy in the treatment of cerebral ischemic injury from four aspects:an overview of mitochondrial autophagy,related signaling pathways,its relationship with cerebral ischemic injury,and the regulatory effects of traditional Chinese medicine.The aim is to provide ideas and references for future basic research and clinical treatment.

Background Arsenic exposure is a common and important environmental and occupational hazardous factor in China, and arsenic-induced insulin resistance (IR) has attracted widespread attention as a negative health outcome to the population. Objective To explore part of the mechanism of hepatic IR induced by arsenic exposure based on the peroxisome proliferators-activated receptors γ (PPARγ)/ glucose transporter 4 (GLUT4) pathway, and to investigate potential effects of Ginkgo biloba extract (GBE) on hepatic IR induced by arsenic exposure and associated mechanism of action. Methods The target of drug action was predicted by network pharmacology and verified by in vivo and in vitro experiments. In vivo experiments: 48 SPF C57BL/6J male mice were divided into 4 groups, including control group, 50 mg·L⁻¹ NaAsO₂ model group (NaAsO₂), 50 mg·L⁻¹ NaAsO₂+10 mg·kg⁻¹ GBE intervene group (NaAsO₂+GBE), and 10 mg·kg⁻¹ GBE group (GBE), 12 mice in each group. The animals were given free access to purified water containing 50 mg·L⁻¹ NaAsO₂, or given intraperitoneal injection of normal saline containing 10 mg·kg⁻¹ GBE once per week. After 6 months of exposure, blood glucose detection, intraperitoneal glucose tolerance test (IPGTT), and insulin tolerance test (ITT) were performed. Serum and liver tissues were collected after the mice were neutralized, liver histopathological sections were obtained, serum insulin levels, liver tissue glycogen content, glucose content were detected by enzyme linked immunosorbent assay (ELISA), and the expression of PPARγ and GLUT4 proteins was detected by Western blot (WB). In vitro experiments: HepG2 cells were divided into 4 groups, including control group, 8 μmol·L⁻¹ NaAsO₂ group (NaAsO₂), 8 μmol·L⁻¹ NaAsO₂ + 200 mg·L⁻¹ GBE intervene group (NaAsO₂+GBE), and 200 mg·L⁻¹ GBE group (GBE). The levels of glycogen and glucose were detected by ELISA, and the expression of PPARγ and GLUT4 proteins was detected by WB. Results A strong binding effect between GBE and PPARγ was revealed by network pharmacology. In in vivo experiments, the NaAsO₂ group exhibited an elevated blood glucose compared to the control group, and the NaAsO₂+GBE group showed a decreased blood glucose compared to the NaAsO₂ group (P<0.01). The histopathological sections indicated severe liver structural damage in the arsenic exposure groups (NaAsO₂ group and NaAsO₂+GBE group), with varying staining intensity, partial liver cell necrosis, and diffuse red blood cell appearance. Both results of in vitro and in vivo experiments showed a decrease in glycogen synthesis and glucose uptake in the NaAsO₂ groups compared to the control groups, which was alleviated in the NaAsO₂+GBE group (P<0.01). The results of WB revealed inhibited PPARγ expression and reduced GLUT4 levels on the cell membrane, and all these changes were alleviated in the NaAsO₂+GBE group (P<0.01). Conclusion This study findings suggest that GBE antagonizes arsenic exposure-induced hepatic IR by regulating the PPARγ/GLUT4 pathway, indicating that GBE has a protective effect on arsenic exposure-induced hepatic IR, and PPARγ may be a potential therapeutic target for arsenic exposure-induced hepatic IR.

Objective:To evaluate the safety and efficacy of domestically produced magnetic sphincter augmentation (MSA) for gastroesophageal reflux disease.Method:This study is a prospective cohort study. Patients with typical heartburn and reflux symptoms (at least partial response to proton pump inhibitors), abnormal esophageal acid exposure and normal esophageal peristalsis were included, prospectively in the Department of Gastroesophageal Surgery, Rocket Force Characteristic Medical Center from June 2019 to September 2022. Patients with hiatal hernia >2 cm and severe esophagitis were excluded. The MSA was wrapped around the distal esophagus after esophageal hiatus repair by laparoscopy. A postoperative questionnaire survey was conducted to assess the relief of symptom, complications, the discontinuation rate of proton pump inhibitor, and surgical satisfaction. Gastroscopy, high-resolution esophageal pressure measurement, and pH value impedance monitoring were also reviewed. The pre- and postoperative rates were compared using the McNeinar χ2 test. Result:Currently, 23 patients with gastroesophageal reflux disease were enrolled and underwent MSA surgery. There were 20 males and 3 females, aged ( M (IQR)) 48 (14) years (range: 25 to 64 years). All cases were successfully implanted with MSA. Subjective indicators were followed for 17 (18) months (range: 14 to 53 months), while objective indicators were followed for 17 (1) months (range: 12 to 23 months). The postoperative gastrointestinal and extraesophageal symptom scores showed a significant decrease compared to preoperative levels as follows: the degree of subjective relief of overall digestive symptoms was 90 (20)% (range:0~100%), the degree of subjective relief of overall respiratory symptoms was 100(10)% (range: 10%~100%), the overall satisfaction rate was 83% (19/23), the proton pump inhibitor discontinuation rate was 70% (16/23). The proportion of esophagitis has decreased from 44% (10/23) to 9% (2/23) ( κ=0.169, P=0.039), The Hill grade of gastroesophageal valve morphology improved from 1 case of grade Ⅰ, 5 cases of grade Ⅱ, 10 cases of grade Ⅲ, and 7 cases of grade Ⅲ preoperative to 22, 1, 0, and 0 cases postoperative. The proportion of lower esophageal sphincter pressure below normal has decreased from 70% (16/23) to 35% (8/23) ( κ=0.170, P=0.012). There were 21 patients who restored normal esophageal acid exposure. Eleven patients had mild long-term dysphagia, but it didn′t affect their daily life. No postoperative device migration, erosion, or secondary surgical removal occurred. Conclusions:Laparoscopic implantation of the MSA device was safe and well tolerated. It can effectively control the symptoms of gastroesophageal reflux disease, reduce medication, restore normal cardia morphology and function, and esophageal acid exposure. The main postoperative complication was dysphagia, but it was relatively mild.