Five saponins were isolated from the kernels of Momordica cochinchinensis, by macroporous resin, silica gel, ODS column chromatography, and semi preparative HPLC. Based on MS and NMR analysis, combining with alkaline hydrolysis and acid hydrolysis, their structures were identified as: gypsogenin-3-O-{β-D-galactopyranosyl (1→2)-[α-L-rhamnopyranosyl (1→3)]-β-D-glucuropyranonosyl}-28-O-β-D-xylopyranosyl (1→3)-[β-D-xylopyranosyl (1→4)]-α-L-rhamnopyranosyl (1→2)-β-D-fucopyranoside (1), quillaic acid-3-O-{β-D-galactopyranosyl (1→2)-[α-L-rhamnopyranosyl (1→3)]-β-D-glucuropyranonosyl}-28-O-β-D-xylopyranosyl (1→3)-[β-D-xylopyranosyl (1→4)]-α-L-rhamnopyranosyl (1→2)-β-D-fucopyranoside (2), gypsogenin-3-O-β-D-galactopyranosyl (1→2)-[α-L-rhamnopyranosyl (1→3)]-β-D-glucuropyranonoside sodium (3), quillaic acid-3-O-β-D-galactopyranosyl (1→2)-[α-L-rhamnopyranosyl (1→3)]-β-D-glucuropyranonoside sodium (4), 18α-quillaic acid-3-O-β-D-galactopyranosyl (1→2)-[α-L-rhamnopyranosyl (1→3)]-β-D-glucuropyranonoside (5). Compounds 1-5 were new compounds, and named as mubezhisides A, B, C, D, E, respectively. They all could obviously inhibited the growth of Candida albicans, C. parapsilosis, and C. tropicalis.

Circadian rhythm is an endogenous biological clock mechanism that enables organisms to adapt to the earth’s alternation of day and night. It plays a fundamental role in regulating physiological functions and behavioral patterns, such as sleep, feeding, hormone levels and body temperature. By aligning these processes with environmental changes, circadian rhythm plays a pivotal role in maintaining homeostasis and promoting optimal health. However, modern lifestyles, characterized by irregular work schedules and pervasive exposure to artificial light, have disrupted these rhythms for many individuals. Such disruptions have been linked to a variety of health problems, including sleep disorders, metabolic syndromes, cardiovascular diseases, and immune dysfunction, underscoring the critical role of circadian rhythm in human health. Among the numerous systems influenced by circadian rhythm, the skin—a multifunctional organ and the largest by surface area—is particularly noteworthy. As the body’s first line of defense against environmental insults such as UV radiation, pollutants, and pathogens, the skin is highly affected by changes in circadian rhythm. Circadian rhythm regulates multiple skin-related processes, including cyclic changes in cell proliferation, differentiation, and apoptosis, as well as DNA repair mechanisms and antioxidant defenses. For instance, studies have shown that keratinocyte proliferation peaks during the night, coinciding with reduced environmental stress, while DNA repair mechanisms are most active during the day to counteract UV-induced damage. This temporal coordination highlights the critical role of circadian rhythms in preserving skin integrity and function. Beyond maintaining homeostasis, circadian rhythm is also pivotal in the skin’s repair and regeneration processes following injury. Skin regeneration is a complex, multi-stage process involving hemostasis, inflammation, proliferation, and remodeling, all of which are influenced by circadian regulation. Key cellular activities, such as fibroblast migration, keratinocyte activation, and extracellular matrix remodeling, are modulated by the circadian clock, ensuring that repair processes occur with optimal efficiency. Additionally, circadian rhythm regulates the secretion of cytokines and growth factors, which are critical for coordinating cellular communication and orchestrating tissue regeneration. Disruptions to these rhythms can impair the repair process, leading to delayed wound healing, increased scarring, or chronic inflammatory conditions. The aim of this review is to synthesize recent information on the interactions between circadian rhythms and skin physiology, with a particular focus on skin tissue repair and regeneration. Molecular mechanisms of circadian regulation in skin cells, including the role of core clock genes such as Clock, Bmal1, Per and Cry. These genes control the expression of downstream effectors involved in cell cycle regulation, DNA repair, oxidative stress response and inflammatory pathways. By understanding how these mechanisms operate in healthy and diseased states, we can discover new insights into the temporal dynamics of skin regeneration. In addition, by exploring the therapeutic potential of circadian biology in enhancing skin repair and regeneration, strategies such as topical medications that can be applied in a time-limited manner, phototherapy that is synchronized with circadian rhythms, and pharmacological modulation of clock genes are expected to optimize clinical outcomes. Interventions based on the skin’s natural rhythms can provide a personalized and efficient approach to promote skin regeneration and recovery. This review not only introduces the important role of circadian rhythms in skin biology, but also provides a new idea for future innovative therapies and regenerative medicine based on circadian rhythms.

Brain organoids are three-dimensional (3D) neural cultures that self-organize from pluripotent stem cells (PSCs) cultured in vitro. Compared with traditional two-dimensional (2D) neural cell culture systems, brain organoids demonstrate a significantly enhanced capacity to faithfully replicate key aspects of the human brain, including cellular diversity, 3D tissue architecture, and functional neural network activity. Importantly, they also overcome the inherent limitations of animal models, which often differ from human biology in terms of genetic background and brain structure. Owing to these advantages, brain organoids have emerged as a powerful tool for recapitulating human-specific developmental processes, disease mechanisms, and pharmacological responses, thereby providing an indispensable model for advancing our understanding of human brain development and neurological disorders. Despite their considerable potential, conventional brain organoids face a critical limitation: the absence of a functional vascular system. This deficiency results in inadequate oxygen and nutrient delivery to the core regions of the organoid, ultimately constraining long-term viability and functional maturation. Moreover, the lack of early neurovascular interactions prevents these models from fully recapitulating the human brain microenvironment. In recent years, the introduction of vascularization strategies has significantly enhanced the physiological relevance of brain organoid models. Researchers have successfully developed various vascularized brain organoid models through multiple innovative approaches. Biological methods, for example, involve co-culturing brain organoids with endothelial cells to induce the formation of static vascular networks. Alternatively, co-differentiation strategies direct both mesodermal and ectodermal lineages to generate vascularized tissues, while fusion techniques combine pre-formed vascular organoids with brain organoids. Beyond biological approaches, tissue engineering techniques have played a pivotal role in promoting vascularization. Microfluidic systems enable the creation of dynamic, perfusable vascular networks that mimic blood flow, while 3D printing technologies allow for the precise fabrication of artificial vascular scaffolds tailored to the organoid’s architecture. Additionally, in vivo transplantation strategies facilitate the formation of functional, blood-perfused vascular networks through host-derived vascular infiltration. The incorporation of vascularization has yielded multiple benefits for brain organoid models. It alleviates hypoxia within the organoid core, thereby improving cell survival and supporting long-term culture and maturation. Furthermore, vascularized organoids recapitulate critical features of the neurovascular unit, including the early structural and functional characteristics of the blood-brain barrier. These advancements have established vascularized brain organoids as a highly relevant platform for studying neurovascular disorders, drug screening, and other applications. However, achieving sustained, long-term functional perfusion while preserving vascular structural integrity and promoting vascular maturation remains a major challenge in the field. In this review, we systematically outline the key stages of human neurovascular development and provide a comprehensive analysis of the various strategies employed to construct vascularized brain organoids. We further present a detailed comparative assessment of different vascularization techniques, highlighting their respective strengths and limitations. Additionally, we summarize the principal challenges currently faced in brain organoid vascularization and discuss the specific technical obstacles that persist. Finally, in the outlook section, we elaborate on the promising applications of vascularized brain organoids in disease modeling and drug testing, address the main controversies and unresolved questions in the field, and propose potential directions for future research.

ObjectiveTo investigate the incidence rate of post-endoscopic retrograde cholangiopancreatography （ERCP） pancreatitis （PEP） in patients with difficult common bile duct intubation undergoing pancreatic duct stenting during surgery， as well as the effect of pancreatic duct stenting in the prevention and treatment of PEP， and to provide a basis for clinical treatment. MethodsA retrospective analysis was performed for the clinical data of 186 patients with biliary tract disease who underwent initial ERCP and had difficult common bile duct intubation in The First Affiliated Hospital of Zhengzhou University from January 2016 to December 2024， and according to the condition of pancreatic duct stenting， the patients were divided into control group with 73 patients （without pancreatic duct stenting）， 5Fr-5 cm stent group with 67 patients， and 7Fr-5 cm stent group with 46 patients. The three groups were compared in terms of baseline data， intraoperative procedures， and postoperative outcomes. A one-way analysis of variance was used for comparison of normally distributed continuous data between multiple groups， and the least significant difference t-test was used for further comparison between two groups； the Kruskal-Wallis H rank sum test was used for comparison of non-normally distributed continuous data between multiple groups， and the Dunn method was used for further comparison between two groups； the chi-square test or the Fisher’s exact test was used for comparison of categorical data between groups. The Logistic regression analysis was used to investigate the influencing factors for PEP in patients with difficult intubation during ERCP. ResultsThe overall incidence rate of PEP was 12.37% （23/186）. Compared with the 5Fr-5 cm stent group and the 7Fr-5 cm stent group， the control group had a significantly higher incidence rate of PEP， a significantly higher score of postoperative abdominal pain， and a significantly longer length of postoperative hospital stay （all P0.01）， and 55.56% of the patients in the control group had moderate-to-severe PEP. The univariate Logistic regression analysis showed that intradiverticular papilla， double guide wire intubation， needle knife precut， the application of basket and balloon for removal of common bile duct stones， intraoperative biopsy， pancreatic duct stenting， intubation time≤10 minutes， frequency of intubation≤5 times， preoperative CRP≤5 mg/L were influencing factors for PEP （all P0.05）， and the multivariate Logistic regression analysis showed that intraoperative pancreatic duct stenting， needle knife precut， and intraoperative biopsy were independent influencing factors for the onset of PEP （all P0.05）. ConclusionPancreatic duct stenting during ERCP can effectively reduce the risk of PEP in patients with difficult intubation， while needle knife precut and intraoperative biopsy can increase the risk of PEP in patients with difficult intubation.

ObjectiveIn nature, objects cast shadows due to illumination, forming the basis for stereoscopic perception. Birds need to adapt to changes in lighting (meaning they can recognize stereoscopic shapes even when shadows look different) to accurately perceive different three-dimensional forms. However, how neurons in the key visual brain area in birds handle these lighting changes remains largely unreported. In this study, pigeons (Columba livia) were used as subjects to investigate how neurons in pigeon’s ventrolateral mesopallium (MVL) represent stereoscopic shapes consistently, regardless of changes in lighting. MethodsVisual cognitive training combined with neuronal recording was employed. Pigeons were first trained to discriminate different stereoscopic shapes (concave/convex). We then tested whether and how light luminance angle and surface appearance of the stereoscopic shapes affect their recognition accuracy, and further verify whether the results rely on specify luminance color. Simultaneously, neuronal firing activity of neurons was recorded with multiple electrode array implanted from the MVL during the presentation of difference shapes. The response was finally analyzed how selectively they responded to different stereoscopic shapes and whether their selectivity was affected by the changes of luminance condition (like lighting angle) or surface look. Support vector machine (SVM) models were trained on neuronal population responses recorded under one condition (light luminance angle of 45°) and used to decode responses under other conditions (light luminance angle of 135°, 225°, 315°) to verify the invariance of responses to different luminance conditions. ResultsBehavioral results from 6 pigeons consistently showed that the pigeons could reliably identify the core 3D shape (over 80% accuracy), and this ability wasn’t affected by changes in light angle or surface appearance. Statistical analysis of 88 recorded neurons from 6 pigeons revealed that 83% (73/88) showed strong selectivity for specific 3D shapes (selectivity index>0.3), and responses to convex shapes were consistently stronger than to concave shapes. These shape-selective responses remained stable across changes in light angle and surface appearance. Neural patterns were consistent under both blue and orange lighting. The decoding accuracy achieves above 70%, suggesting stable responses under different conditions (e.g., different lighting angles or surface appearance). ConclusionNeurons in the pigeon MVL maintain a consistent neural encoding pattern for different stereoscopic shapes, unaffected by illumination or surface appearance. This ensures stable object recognition by pigeons in changing visual environments. Our findings provide new physiological evidence for understanding how birds achieve stable perception (“invariant neural representations”) while coping with variations in the visual field.

OBJECTIVE: To observe the clinical efficacy of Fu's subcutaneous needling based on "multi-joint muscle spiral balance chain" theory for cervical vertigo (CV) and its effect on blood flow velocity of vertebral artery. METHODS: A total of 60 patients with CV were randomized into a Fu's subcutaneous needling group and a medication group, 30 cases in each one. In the Fu's subcutaneous needling group, Fu's subcutaneous needling was delivered at Dazhui (GV14), the flexible tube was retained for 5 min after sweeping manipulation, and the treatment was given once every other day, 3 times a week for 3 weeks. In the medication group, betahistine mesylate tablet and diclofenac sodium dual-release enteric capsule were taken orally for continuous 3 weeks. Before treatment, after treatment, and in follow-up of one month after treatment completion, the scores of dizziness handicap inventory (DHI) and visual analogue scale (VAS) were observed; before and after treatment, the blood flow velocity of vertebral artery was measured by transcranial Doppler, and the clinical efficacy was evaluated after treatment in the two groups. RESULTS: After treatment and in follow-up, each item scores and total scores of DHI were decreased compared with those before treatment in the two groups (P<0.05); the VAS scores after treatment in the two groups, as well as the VAS score in follow-up of the Fu's subcutaneous needling group, were decreased compared with those before treatment (P<0.05). In the Fu's subcutaneous needling group, after treatment and in follow-up, the physical scores and the total scores of DHI, and the VAS scores were lower than those in the medication group (P<0.05); in follow-up, the emotional and functional scores of DHI were lower than those in the medication group (P<0.05). After treatment, the mean blood flow velocity (Vm) of the left vertebral artery (LVA) and the right vertebral artery (RVA) was increased compared with that before treatment in the two groups (P<0.05), and the Vm of LVA and RVA in the Fu's subcutaneous needling group was higher than that in the medication group (P<0.05). The total effective rate was 100.0% (30/30) in the Fu's subcutaneous needling group, which was superior to 73.3% (22/30) in the medication group (P<0.05). CONCLUSION Fu's subcutaneous needling based on the "multi-joint muscle spiral balance chain" theory can effectively alleviate the vertigo and neck pain, and improve the blood flow velocity of vertebral artery in CV patients, and has a long-term therapeutic effect.
Humans ; Female ; Male ; Middle Aged ; Acupuncture Therapy/instrumentation* ; Vertebral Artery/physiopathology* ; Adult ; Vertigo/physiopathology* ; Aged ; Blood Flow Velocity ; Treatment Outcome ; Acupuncture Points ; Young Adult

BACKGROUND: Prospective evidence on how offspring number influences morbidity and mortality remains limited. This study investigated the associations between number of offspring and morbidity and mortality risks among 0.5 million Chinese adults. METHODS: By using data from the China Kadoorie Biobank (CKB; n = 512,723, an approximately 12-year follow-up), sex-stratified phenome-wide association study (PheWAS) analyses were conducted to investigate associations between offspring number (without vs . with offspring; more than one vs . one offspring) and risks of ICD10-coded morbidity and mortality. Sex-specific adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) were estimated by Cox proportional-hazards models. RESULTS: Among 210,129 men and 302,284 women aged 30-79 years, 1,338,837 incident events were recorded. PheWAS results revealed that offspring number was associated with disease risks across multiple systems. Cox models showed that childless men ( vs . one offspring) had higher risks for nine of 36 diseases, while childless women for five of 37. Each additional offspring was associated with reduced risks of mental and behavioral disorders in men (aHR [95% CI] = 0.93 [0.87-0.98]) and both mental and behavioral disorders (aHR [95% CI] = 0.93 [0.89-0.97]) and breast cancer (aHR [95% CI] = 0.82 [0.78-0.86]) in women. However, each additional offspring was associated with a 4% increase in the risk of cholelithiasis and cholecystitis in women (aHR [95% CI] = 1.04 [1.02-1.07]). Among 282,630 patients, 44,533 deaths were documented. Childless patients had higher mortality risk in both men (aHR [95% CI] = 1.37 [1.28-1.47]) and women (aHR [95% CI] = 1.27 [1.15-1.41]). For men, each additional offspring reduced mortality by 4% (aHR [95% CI] = 0.96 [0.95-0.98]), while for women, the lowest risk was observed among those with three to four offspring ( Pnonlinear <0.0001). CONCLUSIONS Offspring number is closely linked to morbidity and mortality risks. Further research is warranted to verify our findings and clarify the underlying mechanisms involved.
Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; China/epidemiology* ; Morbidity ; Proportional Hazards Models ; Prospective Studies ; Risk Factors ; Family Characteristics ; Mortality ; East Asian People

Eucommiae Cortex, the dried bark of Eucommia ulmoides( Eucommiaceae), has both medicinal and edible values.Modern research has shown that Eucommiae Cortex contains various components such as flavonoids, lignans, iridoids, phenolic acids,terpenoids, and steroids, which have anti-osteoporosis, antioxidant, anti-inflammatory, blood glucose-lowering, and gastrointestinal tract-protecting effects. Eucommiae Cortex has applications in multiple fields such as healthcare, industry, and animal husbandry,demonstrating broad development prospects. This article reviews the chemical constituents, pharmacological effects, and quality control status of Eucommiae Cortex. Furthermore, according to the concept of quality marker(Q-marker), this article predicts the Q-markers of Eucommiae Cortex from traditional medicinal properties, traditional medicinal effects, new medicinal effects, measurability of chemical components, compatibility, harvesting periods, and geographical origins. The components such as pinoresinol diglucoside,chlorogenic acid, caffeic acid, quercetin, baicalein, baicalin, olivil, coniferyl ferulate, and kaempferol can be used as Q-markers for Eucommiae Cortex, which provide reference for establishing a systematic quality control system for Eucommiae Cortex.
Eucommiaceae/chemistry* ; Drugs, Chinese Herbal/pharmacology* ; Quality Control ; Humans ; Animals

Buyang Huanwu Decoction(BYHWD), as one of the classic formulas in traditional Chinese medicine(TCM) for the treatment of cerebral ischemic stroke(CIS), has demonstrated definite effects in clinical practice. However, the material basis and mechanism of treatment have not been systematically elucidated. This study employed network pharmacology and molecular docking to analyze the potential targets and mechanisms of blood-and brain-penetrating active components of BYHWD in reducing cell apoptosis in CIS. Cell experiments were then carried out to validate the prediction results. In the experiments, five active components including hydroxysafflor yellow A( HSYA), tetramethylpyrazine( TMP), astragaloside Ⅳ( AS-Ⅳ), amygdalin( AMY), and paeoniflorin(PF) were selected to explore the pharmacological effects of BYHWD. HT22 cells were treated with BYHWD, and the cell counting kit-8(CCK-8) method was employed to examine the toxic and side effects of BYHWD. A cell model of oxygen-glucose deprivation/reoxygenation( OGD/R) was constructed, with apoptosis and pyroptosis as the main screening indicators. The levels of lactate dehydrogenase(LDH) and glutathione(GSH) were measured to assess the cell membrane integrity. Flow cytometry was employed to detect apoptosis, and the activities of caspase-3 and caspase-1 were measured to clarify the status of apoptosis and pyroptosis. ELISA was employed to determine the levels of interleukin(IL)-1β and IL-18 to confirm pyroptosis. HSYA and AMY were identified in this study as the active components regulating apoptosis and pyroptosis. TUNEL was employed to detect the apoptosis rate, and Western blot was employed to determine the expression levels of apoptosis-related proteins B-cell lymphoma-2(Bcl-2), Bcl-2-associated X protein(Bax), and caspase-3, which confirmed that the anti-apoptotic effect of the combined component group was superior to that of the single component groups. The molecular docking results revealed strong binding affinity of HSYA and AMY with SDF-1α and CXCR4.AMD3100, a selective antagonist of CXCR4, was then used for intervention. The results of Western blot showed alterations in the expression levels of apoptosis-associated proteins, SDF-1α, and CXCR4. In conclusion, HSYA and AMY influence cellular apoptosis by modulating the SDF-1α/CXCR4 signaling cascade.
Drugs, Chinese Herbal/chemistry* ; Apoptosis/drug effects* ; Animals ; Neurons/cytology* ; Mice ; Molecular Docking Simulation ; Cell Line ; Glucose/metabolism* ; Humans ; Neuroprotective Agents/pharmacology*