OBJECTIVE: Baicalein has been reported to have wide therapeutic effects that act through its anti-inflammatory activity. This study examines the effect and mechanism of baicalein on sepsis-induced cardiomyopathy (SIC). METHODS: A thorough screening of a small library of natural products, comprising 100 diverse compounds, was conducted to identify the most effective drug against lipopolysaccharide (LPS)-treated H9C2 cardiomyocytes. The core target proteins and their associated signaling pathways involved in baicalein's efficacy against LPS-induced myocardial injury were predicted by network pharmacology. RESULTS: Baicalein was identified as the most potent protective agent in LPS-exposed H9C2 cardiomyocytes. It exhibited a dose-dependent inhibitory effect on cell injury and inflammation. In the LPS-induced septic mouse model, baicalein demonstrated a significant capacity to mitigate LPS-triggered myocardial deficits, inflammatory responses, and ferroptosis. Network pharmacological analysis and experimental confirmation suggested that hypoxia-inducible factor 1 subunit α (HIF1-α) is likely to be the crucial factor in mediating the impact of baicalein against LPS-induced myocardial ferroptosis and injury. By combining microRNA (miRNA) screening in LPS-treated myocardium with miRNA prediction targeting HIF1-α, we found that miR-299b-5p may serve as a regulator of HIF1-α. The reduction in miR-299b-5p levels in LPS-treated myocardium, compared to the control group, was reversed by baicalein treatment. The reverse transcription quantitative polymerase chain reaction, Western blotting, and dual-luciferase reporter gene analyses together identified HIF1-α as the target of miR-299b-5p in cardiomyocytes. CONCLUSION Baicalein mitigates SIC at the miRNA level, suggesting the therapeutic potential of it in treating SIC through the regulation of miR-299b-5p/HIF1-α/ferroptosis pathway. Please cite this article as: Zhou WY, Du JK, Liu HH, Deng L, Ma K, Xiao J, Zhang S, Wang CN. Baicalein attenuates lipopolysaccharide-induced myocardial injury by inhibiting ferroptosis via miR-299b-5p/HIF1-α pathway. J Integr Med. 2025; 23(5):560-575.
Flavanones/pharmacology* ; Animals ; MicroRNAs/genetics* ; Lipopolysaccharides ; Hypoxia-Inducible Factor 1, alpha Subunit/genetics* ; Ferroptosis/drug effects* ; Mice ; Myocytes, Cardiac/metabolism* ; Signal Transduction/drug effects* ; Rats ; Male ; Mice, Inbred C57BL ; Cardiomyopathies/etiology* ; Cell Line ; Sepsis/complications*

Asthenospermia is one of the important causes of male infertility,and its etiology and pathogenesis are complex.Traditional Chinese medicine(TCM)offers unique advantages in treating this disease.The"kidney deficiency and toxic-stasis"theory reveals the dynamic relationship between kidney essence deficiency and the interaction of toxic-stasis in disease pathogenesis,which can be applied clinically to guide the differentiation and treatment of asthenospermia.The formation of asthenospermia is closely related to the deficiency of kidney essence and the blockage of toxic stasis.The kidney essence is the source of reproductive essence.If the kidney essence is depleted for a long time and the kidney essence is deficient,the essence chamber cannot be enriched,resulting in spermatozoa dysfunction and poor spermatozoa mobility.The poison stasis interferes with the spermatozoa and turns into spermatotoxin,which directly harms spermatozoa fertility and leads to the decrease of spermatozoa mobility.Tongjing Jiedu Formula takes tonifying kidney to supply essence,diuresis and detoxification,activating blood circulation and removing blood stasis as the treatment principle,focusing on tonifying kidney to fill essence and nourishing healthy qi to restore the nourishing effect of kidney essence,and also emphasizes clearing heat and detoxification,activating blood circulation and removing blood stasis,promoting diuresis and dredging collaterals to remove poisonous damp-heat and static blood and harmonize blood and vessel,improving spermatogenic environment and improving sperm vitality to help men have children.This article analyzes the application of Tongjing Jiedu Formula in treating asthenospermia from the perspective of"kidney deficiency and toxic stasis",aiming to provid new ideas and methods for the explanation of the pathogenesis of the disease and TCM treatment.

Lung cancer poses a serious threat to global public health security.Chemotherapy,as the main strategy for cancer treatment,faces challenges such as high toxicity and drug resistance.Anticancer peptides have the potential of being developed into new anticancer drugs due to their advantages of broad-spectrum anticancer activity,rapid action,and difficulty in generating drug resistance,but they also face shortcomings such as weak activity and strong toxic side effects.The weakly acidic microenvironment of tumors(pH 6.5-6.8)provides a good idea for the design of anticancer peptides of high-efficiency and low-toxicity.Previously,we designed the acid-sensitive antibacterial peptide pHly-1 using the wolf spider(Lycosa singoriensis)toxin Lycosin-Ⅰ as a template.In this study,we found that pHly-1 also had acid-sensitive anticancer activity.Further alanine scanning analysis of pHly-1 was carried out,and we ob-tained a mutant pHTP-2 with better acid sensitivity,whose IC50(half maximal inhibitory concentration)against A549 cells was 15.68 μmol/L at pH 6.6 and was greater than 100 μmol/L at pH 7.4.At pH 6.6,pHTP-2 could act on various lung cancer cell lines and induce the death of A549 cells by rapid ly-sis;at pH 7.4,500 μmol/L pHTP-2 had weak toxicity to red blood cells(the hemolysis rate was ap-proximately 38％)and primary myocardial cells(the inhibition rate was 49.7％,with P＜0.05).Analy-sis of its charge,particle size,morphology,and secondary structure showed that at pH 6.6,the histidine in the sequence of pHTP-2 was protonated,increasing the positive charge(P＜0.01),decreasing the hy-drated particle size(P＜0.05)and forming an α-helical structure to induce membrane lysis of A549 cells.At pH 7.4,it was deprotonated,the positive charge decreases,a β-sheet structure was formed and self-aggregation occurred,limiting its effect on the A549 cell membrane and showing weak activity.In summary,pHTP-2 could respond to the weakly acidic microenvironment of tumors to exert selective cyto-toxic activity,effectively overcoming the shortcomings of anticancer peptides such as low efficiency and high toxicity.Our findings suggest that it is a high-quality lead molecule for anticancer drugs.

Lung cancer poses a serious threat to global public health security.Chemotherapy,as the main strategy for cancer treatment,faces challenges such as high toxicity and drug resistance.Anticancer peptides have the potential of being developed into new anticancer drugs due to their advantages of broad-spectrum anticancer activity,rapid action,and difficulty in generating drug resistance,but they also face shortcomings such as weak activity and strong toxic side effects.The weakly acidic microenvironment of tumors(pH 6.5-6.8)provides a good idea for the design of anticancer peptides of high-efficiency and low-toxicity.Previously,we designed the acid-sensitive antibacterial peptide pHly-1 using the wolf spider(Lycosa singoriensis)toxin Lycosin-Ⅰ as a template.In this study,we found that pHly-1 also had acid-sensitive anticancer activity.Further alanine scanning analysis of pHly-1 was carried out,and we ob-tained a mutant pHTP-2 with better acid sensitivity,whose IC50(half maximal inhibitory concentration)against A549 cells was 15.68 μmol/L at pH 6.6 and was greater than 100 μmol/L at pH 7.4.At pH 6.6,pHTP-2 could act on various lung cancer cell lines and induce the death of A549 cells by rapid ly-sis;at pH 7.4,500 μmol/L pHTP-2 had weak toxicity to red blood cells(the hemolysis rate was ap-proximately 38％)and primary myocardial cells(the inhibition rate was 49.7％,with P＜0.05).Analy-sis of its charge,particle size,morphology,and secondary structure showed that at pH 6.6,the histidine in the sequence of pHTP-2 was protonated,increasing the positive charge(P＜0.01),decreasing the hy-drated particle size(P＜0.05)and forming an α-helical structure to induce membrane lysis of A549 cells.At pH 7.4,it was deprotonated,the positive charge decreases,a β-sheet structure was formed and self-aggregation occurred,limiting its effect on the A549 cell membrane and showing weak activity.In summary,pHTP-2 could respond to the weakly acidic microenvironment of tumors to exert selective cyto-toxic activity,effectively overcoming the shortcomings of anticancer peptides such as low efficiency and high toxicity.Our findings suggest that it is a high-quality lead molecule for anticancer drugs.

Asthenospermia is one of the important causes of male infertility,and its etiology and pathogenesis are complex.Traditional Chinese medicine(TCM)offers unique advantages in treating this disease.The"kidney deficiency and toxic-stasis"theory reveals the dynamic relationship between kidney essence deficiency and the interaction of toxic-stasis in disease pathogenesis,which can be applied clinically to guide the differentiation and treatment of asthenospermia.The formation of asthenospermia is closely related to the deficiency of kidney essence and the blockage of toxic stasis.The kidney essence is the source of reproductive essence.If the kidney essence is depleted for a long time and the kidney essence is deficient,the essence chamber cannot be enriched,resulting in spermatozoa dysfunction and poor spermatozoa mobility.The poison stasis interferes with the spermatozoa and turns into spermatotoxin,which directly harms spermatozoa fertility and leads to the decrease of spermatozoa mobility.Tongjing Jiedu Formula takes tonifying kidney to supply essence,diuresis and detoxification,activating blood circulation and removing blood stasis as the treatment principle,focusing on tonifying kidney to fill essence and nourishing healthy qi to restore the nourishing effect of kidney essence,and also emphasizes clearing heat and detoxification,activating blood circulation and removing blood stasis,promoting diuresis and dredging collaterals to remove poisonous damp-heat and static blood and harmonize blood and vessel,improving spermatogenic environment and improving sperm vitality to help men have children.This article analyzes the application of Tongjing Jiedu Formula in treating asthenospermia from the perspective of"kidney deficiency and toxic stasis",aiming to provid new ideas and methods for the explanation of the pathogenesis of the disease and TCM treatment.

Objective: Primary frozen shoulder causes significant pain and progressively restricts shoulder movements. Diagnosis is made clinically based on patient history and physical examination. Management is mainly non-invasive owing to its self-limiting clinical course. However, clinical practice guidelines for frozen shoulder have not yet been developed in Korea. The developed guidelines aim to provide evidence-based recommendations for the diagnosis and treatment of frozen shoulder. Methods: A guideline development committee reviewed the literature from four databases (PubMed, Embase, Cochrane Library, and KMbase). Using the Population, Intervention, Comparator, and Outcome (PICO) framework, the committee formulated two backgrounds and 16 key questions to address common clinical concerns. Recommendations were made using the Grading of Recommendations, Assessment, Development, and Evaluation framework. Results: Diabetes, thyroid disease, and dyslipidemia significantly increase the risk of developing a frozen shoulder. Although frozen shoulder is often self-limiting, some patients may experience long-term functional disabilities. Ultrasound and magnetic resonance imaging should be used as adjunctive tools alongside clinical diagnosis, and rather than as independent diagnostic methods. Noninvasive approaches, such as medications, physical modalities, exercises, electrical stimulation, and manual therapy, may reduce pain and improve shoulder function. Other noninvasive interventions have limited evidence, and their application should be based on clinical judgment. Intra-articular steroid injections are recommended for treatment, and physiotherapy or hydrodilation with steroid injections can also be beneficial. Conclusion These guidelines provide evidence-based recommendations for diagnosing and treating primary frozen shoulder.

Male infertility (MI) and male sexual dysfunction (MSD) can often coexist together due to various interplay factors such as psychosexual, sociocultural and relationship dynamics. The presence of each form of MSD can adversely impact male reproduction and treatment strategies will need to be individualized based on patients’ factors, local expertise, and geographical socioeconomic status. The Asia Pacific Society of Sexual Medicine (APSSM) and the Asian Society of Men’s Health and Aging (ASMHA) aim to provide a consensus statement and practical set of clinical recommendations based on current evidence to guide clinicians in the management of MI and MSD within the Asia-Pacific (AP) region. A comprehensive, narrative review of the literature was performed to identify the various forms of MSD and their association with MI. MEDLINE and EMBASE databases were searched for the following English language articles under the following terms: “low libido”, “erectile dysfunction”, “ejaculatory dysfunction”, “premature ejaculation”, “retrograde ejaculation”, “delayed ejaculation”, “anejaculation”, and “orgasmic dysfunction” between January 2001 to June 2022 with emphasis on published guidelines endorsed by various organizations. This APSSM consensus committee panel evaluated and provided evidence-based recommendations on MI and clinically relevant MSD areas using a modified Delphi method by the panel and specific emphasis on locoregional socioeconomic-cultural issues relevant to the AP region. While variations exist in treatment strategies for managing MI and MSD due to geographical expertise, locoregional resources, and sociocultural factors, the panel agreed that comprehensive fertility evaluation with a multidisciplinary management approach to each MSD domain is recommended. It is important to address individual MI issues with an emphasis on improving spermatogenesis and facilitating reproductive avenues while at the same time, managing various MSD conditions with evidence-based treatments. All therapeutic options should be discussed and implemented based on the patient’s individual needs, beliefs and preferences while incorporating locoregional expertise and available resources.

Knowledge about the neuronal dynamics and the projectome are both essential for understanding how the neuronal network functions in concert. However, it remains challenging to obtain the neural activity and the brain-wide projectome for the same neurons, especially for neurons in subcortical brain regions. Here, by combining in vivo microscopy and high-definition fluorescence micro-optical sectioning tomography, we have developed strategies for mapping the brain-wide projectome of functionally relevant neurons in the somatosensory cortex, the dorsal hippocampus, and the substantia nigra pars compacta. More importantly, we also developed a strategy to achieve acquiring the neural dynamic and brain-wide projectome of the molecularly defined neuronal subtype. The strategies developed in this study solved the essential problem of linking brain-wide projectome to neuronal dynamics for neurons in subcortical structures and provided valuable approaches for understanding how the brain is functionally organized via intricate connectivity patterns.
Animals ; Neurons/physiology* ; Mice ; Brain/physiology* ; Mice, Inbred C57BL ; Somatosensory Cortex/physiology* ; Neural Pathways/physiology* ; Hippocampus/physiology* ; Mice, Transgenic ; Male ; Brain Mapping ; Nerve Net/physiology* ; Substantia Nigra/physiology* ; Tomography, Optical/methods*

Objective To understand the current situation of human brain donation in Hebei Province by analyzing the basic information of Human Brain Bank samples of Hebei Medical University in order to provide basic data support for subsequent scientific research.Methods The samples collected from the Human Brain Bank of Hebei Medical University were analyzed(from December 2019 to February 2024),including gender,age,cause of death,as well as quality control data such as postmortem delay time,pH value of cerebrospinal fluid and and RNA integrity number and result of neuropathological diagnosis.Results Until February 2024,30 human brain samples were collected and stored in the Human Brain Bank of Hebei Medical University,with a male to female ratio of 9∶1.Donors over 70 years old accounted for 53％.Cardiovascular and cerebrovascular diseases(36.67％)and nervous system diseases(23.33％)accounted for a high proportion of the death causes.The location of brain tissue donors in Shijiazhuang accounted for 90％donations,and the others were from outside the city.The postmortem delay time was relatively short,90％within 12 hours and 10％more than 12 hours.69.23％of the brain samples had RNA integrity values greater than 6.Cerebrospinal fluid pH values ranged from 5.8 to 7.5,with an average value of 6.60±0.45.Brain weights ranged from 906-1496 g,with an average value of(1210.78±197.84)g.Three apolipoprotein E(APOE)alleles were detected including five genotypes(ε2/ε3,ε2/ε4,ε3/ε3,ε3/ε4,ε4/ε4).Eleven staining methods related to neuropathological diagnosis had been established and used.A total of 12 cases were diagnosed as neurodegenerative diseases(including Alzheimer's disease,Parkinson's disease,multiple system atrophy,corticobasal degeneration and progressive supranuclear palsy,etc.),accounting for 40％donated brains.The comorbidity rate of samples over 80 years old was 100％.Conclusion The summary and analyses of the data of brain donors in the Human Brain Bank of Hebei Medical University can reflect the current situation of the construction and operation of the brain bank in Hebei Province,and it can also be more targeted to understand and identify potential donors.Our information can provide reference for the construction of brain bank and provides more reliable materials and data support for scientific research.

To conduct textual research on the records of Chrysanthemi Flos in the ancient literature from the aspects of name， origin， species， scientific name， origin， harvesting， processing， quality and so on， and the modern literature was sorted out to clarify the relationship between the ancient and modern times， so as to provide a reference for the development of famous classical formulas containing Chrysanthemi Flos. Chrysanthemi Flos is an ornamental， edible and medicinal plant in China， it has many aliases， but it has been recorded in this materia medica under the name of Juhua， Ganju and Ganjuhua. Before the Tang dynasty， medicinal Chrysanthemi Flos mainly collected wild products， including yellow flowers and white flowers， of which the mainstream of yellow flowers was originally Dendranthema lavandulifolium and D. potentilloides， the mainstream of white flowers is D. vestitum and D. chanetii. The cultivation of medicinal Chrysanthemi Flos began in the Northern Song dynasty， and wild D. lavandulifolium， D. potentilloides， D. vestitum and D. chanetii were selected through long-term interspecies and intraspecies crossbreeding， which gradually formed the current cultivar D. morifolium. After chrysanthemums were introduced abroad， foreign scholars began to name chrysanthemums with Linnaeus's plant classification system. In 1792， Mathier named chrysanthemums as Chrysanthemum morifolium and continued to this day， and all the editions of Chinese Pharmacopoeia adopted this scientific name. In the Song dynasty， many local varieties such as Nanyangju， Dengzhouhuang and Dengzhoubai appeared. By the time of the Republic of China， five famous authentic varieties， namely Huaiju， Boju， Chuju， Gongju and Hangju， had been cultivated for medicinal purposes. Boju has been the best medicinal variety since the late Qing dynasty. Hangbaiju has been famous for its tea use， especially the best quality of Huju. Chuju has its own unique characteristics， and it is of good quality both for medicine and tea. Gongju has always been a good tea chrysanthemum. Chrysanthemums are traditionally harvested in September of the lunar calendar， but some of the new varieties cultivated nowadays are harvested earlier. The embryo chrysanthemum in Hangbaiju is a commodity type that collects unopened buds in advance. In ancient times， chrysanthemums were mainly dried in the shade， in modern times， drying methods include drying in the shade， drying in the oven and drying in the sun after steaming. At present， hot air drying is mostly used. In terms of processing， Chrysanthemi Flos was used raw products in ancient times， in modern times， it is still widely used， sometimes stir fried（including stir-fried charcoal）. Due to different varieties， producing areas and processing methods， there are certain differences in the proportion of ingredients contained in chrysanthemum. Therefore， it is suggested that chrysanthemums with different varieties， origins and processing methods should be selected according to clinical indications in the development of famous classical formula preparations containing Chrysanthemi Flos.