This article systematically analyzes the historical evolution of the name， medicinal parts， origin， harvesting， processing and other aspects of Houttuyniae Herba（HH） by referring to the medical books， prescription books and other documents of the past dynasties， combined with the research materials related to modern and contemporary times， in order to provide a basis for the development of famous classical formulas containing this herb. In ancient literature， HH was often referred to as "Ji" and "Jicai"， the name of "Ji" was first recorded in Mingyi Bielu during the Han and Wei dynasties， and the name of Yuxingcao was first seen in Lyuchanyan Bencao during the southern Song dynasty and has continued to this day. The origin of HH used throughout history is consistent， all of which are the whole herb or aboveground parts of Houttuynia cordata in Saururaceae family. HH recorded throughout history has a wide range of production areas， mostly self-produced self-marketing. In ancient times， fresh HH was often used as medicine by pounding its juice without involving any processing steps. Both fresh and dried products can be used as medicine， the fresh products uses the whole plant， while the dried products uses the aboveground parts， which are cleaned， selected and processed before use. Fresh products are harvested regardless of season， while dried products are harvested in both summer and autumn， with summer as the best. In ancient times， there were no specific requirements for the quality of HH， while in modern times， "intact stems and leaves with a strong fishy smell" are preferred. In addition， the medicinal properties of HH have undergone significant changes from ancient to modern times. In the early period， it was believed that its medicinal property was slightly warm， until the 1977 edition of Chinese Pharmacopoeia officially changed it to slightly cold. Both ancient and modern literature states that HH can be used for the treatment of carbuncle and malignant sores， Lyuchanyan Bencao for the first time introduced HH fresh juice can relieve summer heat， since Diannan Bencao recorded that it can be used for lung carbuncle， and gradually developed into the first choice for the treatment of lung carbuncle. Based on the research results， it is suggested that fresh herb or dried aboveground parts of H. cordata are used as medicine when developing famous classical formulas.

OBJECTIVES: To study the molecular mechanisms of LDH-loaded si-NEAT1 for regulating paclitaxel resistance and tumor-associated macrophage (TAM) polarization in breast cancer. METHODS: qRT-PCR and Western blotting were used to detect the expression of lncRNA NEAT1, miR-133b, and PD-L1 in breast cancer SKBR3 cells and paclitaxel-resistant SKBR3 cells (SKBR3-PR). The effects of transfection with si-NEAT1 and miR-133b mimics on MRP, MCRP and PD-L1 expressions and cell proliferation, migration and apoptosis were investigated using qRT-PCR, Western blotting, scratch and Transwell assays, and flow cytometry. Rescue experiments were conducted using si-NEAT1 and miR-133b inhibitor. Human THP-1 macrophages were cultured in the presence of conditioned media (CM) derived from SKBR3 and SKBR3-PR cells with or with si-NEAT1 transfection for comparison of IL-4-induced macrophage polarization by detecting the surface markers. LDH@si-NEAT1 nanocarriers were constructed, and their effects on MRP, MCRP and PD-L1 expressions and cell behaviors of the tumor cells were examined. THP-1 cells were treated with the CM from LDH@si-NEAT1-treated tumor cells, and the changes in their polarization were assessed. RESULTS: SKBR3-PR cells showered significantly upregulated NEAT1 and PD-L1 expressions and lowered miR-133b expression as compared with their parental cells. Transfection with si-NEAT1 and miR-133b mimics inhibited viability, promoted apoptosis and enhanced MRP and BCRP expressions in SKBR3-PR cells. NEAT1 knockdown obvious upregulated miR-133b and downregulated PD-L1, MRP and BCRP expressions. The CM from SKBR3-PR cells obviously promoted M2 polarization of THP-1 macrophages, which was significantly inhibited by CM from si-NEAT1-transfected cells. Treatment with LDH@si-NEAT1 effectively inhibited migration and invasion, promoted apoptosis, and reduced MRP, BCRP and PD-L1 expressions in the tumor cells. The CM from LDH@si-NEAT1-treated SKBR3-PR cells significantly downregulated Arg-1, CD163, IL-10, and PD-L1 and upregulated miR-133b expression in THP-1 macrophages. CONCLUSIONS LDH@si-NEAT1 reduces paclitaxel resistance of breast cancer cells and inhibits TAM polarization by targeting the miR-133b/PD-L1 axis.
Humans ; MicroRNAs/genetics* ; RNA, Long Noncoding/genetics* ; Paclitaxel/pharmacology* ; Breast Neoplasms/metabolism* ; Drug Resistance, Neoplasm ; B7-H1 Antigen/metabolism* ; Cell Line, Tumor ; Female ; Tumor-Associated Macrophages ; Apoptosis ; Cell Proliferation ; Macrophages ; Cell Movement

Microorganisms, abundant in nature, are prolific producers of a diverse array of natural products (NPs) that are fundamental in the development of innovative therapeutics. Despite their significant potential, the field faces considerable challenges, including the continuous emergence of potential health threats, as well as novel pathogen strains and viruses. The advent and implementation of advanced technologies, such as culture strategies, genomics mining, and artificial intelligence (AI), are facilitating a paradigm shift in pharmaceutical research, introducing innovative methodologies and perspectives. The development and maturation of these technologies have enhanced the exploration of microbial-derived NPs, thereby advancing pharmaceutical research and development. This review synthesizes recent developments in this context, emphasizing their applications in pharmaceutical discovery and development. Through systematic analysis and synthesis, it provides objective insights into the promising prospects and future direction of this essential field.
Biological Products/chemistry* ; Drug Discovery ; Humans ; Artificial Intelligence ; Bacteria/metabolism*

Objective To explore the mechanism by which zinc-regulated transporters, iron-regulated transporter-likeprotein 4 (ZIP4) regulates glycolysis and its impact on tumor progression in cholangiocarcinoma (CCA), providing a theoretical basis for targeted therapy of CCA. Methods ZIP4 expression in CCA was analyzed using the GEPIA database. Immuno-histochemistry (IHC) was used to detect ZIP4 expression in 20 paired CCA and adjacent non-tumor tissues. Stable ZIP4-overexpressing CCA cell lines (ZIP4-OE) were established. Gene set enrichment analysis was used to screen differentially expressed genes and pathways in ZIP-OE CCA cells. ZIP4, N-myc proto-oncogene protein (MYCN), and histone-lysine N-methyltransferase 2E (KMT2E) were knocked down using small interfering RNAs (siRNAs). The expression of glycolysis-related gene (glucose transporter 1 [Glut1], hexokinase 2 [HK2], and lactate dehydrogenase A [LDHA]) was measured by real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR). Glycolytic activity was assessed by measuring the extracellular acidification rate (ECAR). Cell proliferation was evaluated using colony formation assays, and cell migration was assessed using Transwell assays. A xenograft mouse model was constructed to examine CCA tumor growth. Protein levels of ZIP4, KMT2E, H3K4me3 (tri-methylation of lysine 4 on histone H3), and MYCN were detected by Western blotting. Results GEPIA database analysis and IHC results confirmed significantly higher ZIP4 expression levels in CCA tissues compared to adjacent non-tumor tissues (P＜0.05). Compared to the control group, the ZIP4-OE group exhibited a significantly increased ECAR, along with significantly enhanced proliferation and migration abilities (P＜0.01). Conversely, knockdown of ZIP4 suppressed CCA cells proliferation and migration. GEPIA analysis indicated that ZIP4 upregulates the transcription of oncogene MYCN, as well as glycolysis-related genes. Knockdown of MYCN abolished the ZIP4 overexpression-induced upregulation of Glut1, HK2, and LDHA gene transcription, reduced glycolysis, and significantly inhibited CCA cell proliferation and migration (P＜0.05). Mechanistic studies demonstrated that ZIP4 increases H3K4me3 level via KMT2E, leading to MYCN transcription. Knockdown of KMT2E in CCA cells suppressed the ZIP4 overexpression-induced enhancement in H3K4me3 modification, resulting in MYCN downregulation and significantly reduced CCA cells proliferation and migration (P＜0.05). Conclusions ZIP4 upregulates H3K4me3 modification through KMT2E, which recruits transcription factors to activate the transcription of MYCN. This subsequently enhances cellular glycolysis and promotes the proliferation and migration of CCA cells.

Acute urinary retention(AUR)occurs frequently among astronauts on orbit.The current treatment is complex and easy to damage the urethra,which seriously affects the life and work of astronauts.In contrast,acupuncture,a traditional Chinese remedy,has shown promising results in managing urinary retention.However,the specific acupoints that could potentially prevent AUR remain uncertain due to the unique physiological conditions experienced by individuals in space compared to those on Earth.To address this gap,our research delved into the mechanisms of AUR and acupuncture within both traditional Chinese medicine and modern medical practices.We conducted a thorough literature review from Pubmed,Web of Science,CNKI,Wanfang database,VIP database and Chinese Medical Code database.A hierarchical evidence-scoring approach was utilized to analyze the included literatures,thus devised acupuncture protocols for the treatment of AUR.The outcomes of our study aim to establish a foundation for the application of acupuncture in managing AUR.

Under the influence of long-term space flights and the confined space environment,it is very easy to induce space depression syndrome,mainly manifested as decreased emotional stability,sleep disorders,mental fatigue,etc.,which seriously affect the living conditions and working abilities of astronauts.The current treatment methods mainly focus on psychological support and drug intervention.Acupuncture has a good effect in treating depression.Therefore,starting from the TCM pathogenesis and modern medical pathogenesis of aerospace depression syndrome,we conducted literature retrieval from databases such as the Chinese Medical Classic,China National Knowledge Infrastructure(CNKI),Wanfang,VIP,PubMed,and Web of science.For the included literature,we adopted the stratified evidence scoring method and combined the TCM mechanism and modern medical mechanism of the effect of acupuncture.A prescription for acupuncture points was constructed to provide a basis for selecting acupuncture points for the prevention of aerospace depression syndrome through acupuncture.

The health problems of operators who are not adapted to the special environment of sailing and diving.Ships and submarines are far away from the coast,medical resources are limited,at present the main use of drugs to prevent and control related diseases,but the actual application of the effect is not ideal,many drugs in the treatment of disease at the same time,it will make the operating personnel to produce drowsiness,decreased concentration or drug allergies and other adverse reactions,affecting the implementation of the mission of long-distance voyage.Traditional Chinese medicine focuses on the overall concept,can mobilize the body's self-repair ability,the ability to adapt to the external environment,in the prevention and treatment of disease at the same time,can regulate the body's internal organs function,safeguard the body's function,to ensure the effectiveness of the operator's work,and many of the interventions of traditional Chinese medicine is simple and easy to carry out,is not confined to the environmental limitations of the navigation and diving medicine has a very strong applicability.In this paper,we discuss the mechanism of Traditional Chinese medicine in the body under the environment of navigation and diving,summarize the current status of the application of Traditional Chinese medicine in navigation and diving medicine,and look forward to the future direction of the application of Traditional Chinese medicine,in order to provide a new way of thinking for the research of navigation and diving medicine with Chinese characteristics.

Objective To investigate whether transcutaneous electrical acupoint stimulation(TEAS)can improve the muscle strength,endurance and work efficiency of calf muscles in healthy young men,aiming to explore a new method for preventing and combating microgravity-induced muscle atrophy in space environments.Methods 40 healthy young men aged 18-35 years were randomly divided into a Control group(Pseudo Transcutaneous Electrical Acupoint Stimulation)and a Experimental group(Transcutaneous Electrical Acupoint Stimulation)in a 1∶1 ratio,with 20 participants in each group.In the Control group,the indicator light of the stimulator was covered,and the device was turned on,but the electrodes did not contact the skin,The device automatically turned offafter 3 seconds.In the Experimental group,the TEAS device was connected to the current and TEAS intervention was performed.The electrical stimulation waveform was a sperse-dense wave with a frequency of 4/20 Hz,and the intensity was determined by patient tolerance.The acupoints selected for electrical stimulation in both groups were bilateral Zusanli(ST36)、Liangqiu(ST34),Taixi(KI3),and Fuliu(KI7).Zusanli and Liangqiu were paired,and Taixi and Fuliu were paired.The intervention frequency was 30 min/time,1 time/day,6 days/week,for 2 weeks.The relative peak torque at 60°/s,relative peak torque at 180°/s,and average power at 180°/s of the bilateral calf muscles were measured using an isokinetic dynamometer at 0th,7th,and 14d day of the experiment.Results After 1 week of TEAS,compared with Control group,there were no significant changes in the relative peak torque at 60°/s,relative peak torque at 180°/s and average power at 180°/s of the bilateral anterior calf muscles in the Experimental group(all P>0.05);however,compared with Control group,the relative peak torque at 60°/s and the relative peak torque at 180°/s of the bilateral posterior calf muscles in the Experimental group were significantly increased(all P<0.05).After 2 weeks TEAS;compared with the Control group,there were no significant changes in the relative peak torque at 60°/s,relative peak torque at 180°/s and average power at 180°/s of the bilateral anterior calf muscles in the Experimental group(all P>0.05);however,the relative peak torque at 60°/s,relative peak torque at 180°/s,and average power at 180°/s of the bilateral posterior calf muscles were significantly increased in the Experimental group(all P<0.05).Conclusion TEAS of Zusanli,Liangqiu,Fuliu and Taixi acupoints on the lower limbs for 2 weeks can effectively improve the maximum muscle strength,endurance and work efficiency of the posterior calf muscles in healthy young men.

This paper reviews the published articles of recent years on the application of deep learning methods in automatic localization of acupoint, and summarizes it from 3 key links, i.e. the dataset construction, the neural network model design, and the accuracy evaluation of acupoint localization. The significant progress has been obtained in the field of deep learning for acupoint localization, but the scale of acupoint detection needs to be expanded and the precision, the generalization ability, and the real-time performance of the model be advanced. The future research should focus on the support of standardized datasets, and the integration of 3D modeling and multimodal data fusion, so as to increase the accuracy and strengthen the personalization of acupoint localization.
Deep Learning ; Acupuncture Points ; Humans ; Neural Networks, Computer

Based on a letrozole-induced rat model of polycystic ovary syndrome (PCOS), serum metabolomics was employed to characterize metabolic abnormalities, identify potential biomarkers, and investigate their roles in the pathogenesis and progression of PCOS. Metabolomic analyses revealed significantly decreased levels of cholesterol, pregnenolone, leucine, and citrate in the serum of model rats, accompanied by elevated levels of androsterone glucuronide (ADTG) and linoleic acid, indicating dysregulation of key pathways including steroid biosynthesis, branched-chain amino acid metabolism, tricarboxylic acid (TCA) cycle, and lipid metabolism. To elucidate the tissue origins and molecular mechanisms underlying these metabolic alterations, ovarian proteomics and qRT-PCR analyses were further integrated. The results confirmed the upregulation of key enzymes involved in the related metabolic pathways, such as 17α-hydroxylase (CYP17A1), 11β-hydroxysteroid dehydrogenase (HSD11B1), branched-chain amino acid aminotransferase (BCAT2), fatty acid desaturase 2 (FADS2), and oxoglutarate dehydrogenase (OGDH). These findings suggest that both “cholesterol precursor depletion-androgen accumulation” and “energy/lipid metabolic reprogramming” constitute core features of metabolic disturbances in PCOS. Through multi-omic cross-validation, six serum metabolites with high stability and clinical translational potential were identified as promising combinational biomarkers for the auxiliary diagnosis of PCOS. This study employed a metabolomics-guided strategy, supported by proteomic and transcriptomic validation, which has not only deepened our understanding of PCOS metabolic mechanisms but also provided us with a theoretical foundation for its auxiliary diagnosis.