ObjectiveThis paper aims to clarify the material basis of Gualou Niubangtang and establish a quantitative analysis method for its main constituents， providing a reference for the overall quality control of this preparation. MethodsThe constituents in the formula were systematically characterized based on ultra-performance liquid chromatography-quadrupole time-of-flight tandem mass spectrometry （UPLC-Q-TOF-MS/MS）. Identification was performed by matching with the UNIFI 9.6 software and utilizing database platforms such as PubChem， ChemicalBook， and ChemSpider， combined with relevant literature reports. A quantitative analysis method for the seven main constituents in Gualou Niubangtang was established by using high performance liquid chromatography （HPLC）. ResultsUPLC-Q-TOF-MS/MS analysis identified 155 constituents， including 69 flavonoids， 36 terpenoids， 23 phenylpropanoids， 8 phenylethanoid glycosides， and 19 other types of constituents. In the established quantitative analysis method， the seven main constituents showed good linearity within their respective linear ranges. The precision， repeatability， stability， and spike recovery all met the required standards. The results showed that the content ranges of geniposide， liquiritin， hesperidin， arctiin， baicalin， oroxylin A-7-O-β-D-glucuronide， and wogonoside in 15 batches of Gualou Niubangtang were 13.67-21.25， 1.20-7.64， 5.45-7.45， 22.97-33.51， 29.95-39.07， 2.58-4.80， and 6.56-9.31 mg·g^-1， respectively. ConclusionThis study successfully characterizes and attributes multi-category constituents in Gualou Niubangtang， clarifying that its material basis is primarily composed of flavonoids， terpenoids， phenylethanoid glycosides， and phenylpropanoids. Furthermore， it enables the quantification of seven constituents within the formula. This work lays a foundation for research on the quality control， action mechanism， and clinical application of this formula.

Objective To evaluate the efficacy of combining the replenishing qi and nourishing yin empirical formula with anti-vascular endothelial growth factor (VEGF) in diabetic macular edema (DME). Methods A retrospective analysis was conducted on 59 patients diagnosed with DME at Tongji Hospital of Tongji University or Shanghai Nanxiang Hospital, Jiading District from June 2019 to December 2022. Among them, 29 cases received intravitreal injection of ranibizumab (anti-VEGF group), while 30 cases received both intravitreal injection of ranibizumab and oral administration of the replenishing qi and nourishing yin empirical formula (combined treatment group). The best corrected visual acuity (BCVA), central macular thickness (CMT), and the traditional Chinese medicine (TCM) syndrome score were compared between the two groups before treatment and at 4, 8, 12, 16, 20, and 24 weeks after treatment. Results Compared with before treatment, BCVA significantly improved (P＜0.05) and CMT significantly decreased (P＜0.05) at different time points after treatment in both groups. At 16, 20, and 24 weeks after treatment, BCVA in the combined treatment group was superior to that in the anti-VEGF group (P＜0.01). At 12, 16, 20, and 24 weeks after treatment, CMT in the combined treatment group was lower than that in the anti-VEGF group (P＜0.01). Starting from week 8 after treatment, the TCM syndrome scores in the combined treatment group were lower than those in the anti-VEGF group (P＜0.01). Conclusions The replenishing qi and nourishing yin empirical formula could improve the efficacy of anti-VEGF therapy in DME patients, indicating that integrating traditional Chinese and Western medicine has certain clinical application value in treating DME.

Objective: To investigate the recreational use status of electronic products among high school students in Shanxi Province and the influencing factors for excessive use, so as to provide insights into the promotion of rational use of electronic products among high school students. Methods: The high school students from 117 schools in Shanxi Province were selected using the stratified random sampling method, and basic information, lifestyle behaviors and recreational use of electronic products were collected using questionnaire surveys. The prevalence of excessive recreational use of electronic products was analyzed, and the factors affecting excessive recreational use of electronic products among high school students were analyzed using a multivariable logistic regression model. Results: A total of 13 804 valid questionnaires were recoverd, with an effective rate of 98.32%. There were 6 634 males (48.06%) and 7 170 females (51.94%), with a median age of 17.00 (interquartile range, 1.00) years. There were 7 024 students in Grade One (50.88%) and 6 780 students in Grade Two (49.12%). The prevalence of recreational use of electronic products was 14.18% (1 958 cases). Multivariable logistic regression analysis showed that males (OR=1.461, 95%CI: 1.325-1.611), students in Grade Two (OR=1.720, 95%CI: 1.559-1.897), students whose parents had below high school education (OR=1.391, 95%CI: 1.156-1.674), students without parental support (OR=1.281, 95%CI: 1.078-1.523), students not living on campus (OR=1.142, 95%CI: 1.026-1.271), students without myopia (OR=1.121, 95%CI: 1.008-1.248), and students with sufficient sleep (OR=1.162, 95%CI: 1.054-1.281) had a higher risk of excessive recreational use of electronic products. Conclusion The prevalence of excessive recreational use of electronic products among high school students in Shanxi Province was relatively high, which was related to gender, grade, parental education, parental attitudes, boarding status, myopia and sleep quality.

Amyloid-β peptide （Aβ） is considered a major cause of Alzheimer's disease （AD）. However， current researches emphasize that Aβ can activate microglia and astrocytes， which causes neuroinflammation. Neuroinflammation plays a crucial role in the neuronal mortality process， and can be considered the underlying cause of AD. In addition， vascular damage was proposed to play an important role in the pathogenesis of AD more than two decades ago， but few researchers have focused on the positive role of cerebrovascular damage in AD. In recent years， a growing body of evidence has supported that brain microvascular injury causes the occurrence of AD. Moreover， recent research indicated that inflammation caused by brain microvascular injury is also a significant risk factor for the development of AD. In damaged microvessels， C-reactive protein （CRP） is a non-specific inflammatory marker， which can activate the complement and enhance phagocytosis of immune cells， and help to eliminate pathogenic microorganisms from the body. The plenty of evidence indicated that CRP penetrated brain tissue and participated in neuroinflammation during brain microvascular injury， thereby influencing the pathogenesis of AD. Therefore， the negative effects of CRP and Aβ on the pathogenesis of AD are equally important. At present， few researchers have established a link between the effects of CRP and Aβ on AD and conducted in-depth analysis. This article firstly and deeply analyzed and summarized the significant function and connection of Aβ and CRP in AD， which provided support for the theory that neuronal cerebrovascular injury is the cause of AD.

Despite the groundbreaking advances in cancer immunotherapy achieved by immune checkpoint inhibitors (ICIs), their efficacy remains limited by the immunosuppressive tumor microenvironment (TME). Yes-associated protein (YAP) and transcriptional coactivator with PDZ-binding motif (TAZ), key effectors of the Hippo signaling pathway, play pivotal roles in tumor immune evasion. They directly regulate the expression of immune checkpoints, mediate the formation of an immunosuppressive microenvironment, inhibit T cell function, and interact with other signaling pathways to promote immune escape. Diverse strategies targeting YAP/TAZ have been developed, including direct inhibition, modulation of upstream regulators, and suppression of downstream target genes. Preclinical studies have demonstrated that combining YAP/TAZ inhibition with ICIs significantly enhances therapeutic efficacy across various tumor models. This review summarizes recent advances in understanding the role of YAP/TAZ in immune evasion within the TME and explores the potential of targeting this pathway to improve immunotherapy outcomes. Furthermore, it discusses the translational value of combination therapies based on YAP/TAZ inhibition, providing a theoretical framework and practical guidance for the development of innovative immunotherapeutic strategies and precision medicine approaches.
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Humans ; Immunotherapy/methods* ; Neoplasms/metabolism* ; Signal Transduction/drug effects* ; Adaptor Proteins, Signal Transducing/immunology* ; Animals ; Transcriptional Coactivator with PDZ-Binding Motif Proteins ; Transcription Factors/immunology* ; YAP-Signaling Proteins ; Tumor Microenvironment

Gelsemium elegans (G. elegans) is an extremely poisonous plant that is widely distributed in southern China and southeastern Asia. G. elegans poisoning events occur frequently in southern China, and are therefore an urgent public health problem requiring multidisciplinary action. However, the toxic components and toxicological mechanisms remain unclear. Here, we describe a systematic investigation on the toxic components of G. elegans, resulting in the isolation and identification of 120 alkaloids. Based on acute toxicity screening, the structure-toxicity relationship of Gelsemium alkaloids was proposed for the first time. Moreover, gelsedine- and humantenine-type alkaloids were detected in the clinical blood sample, and were confirmed to be causative in the poisoning. The most toxic compound, gelsenicine (1), had selective inhibitory effects toward ventral respiratory group (VRG) neurons in the medulla, which is the main brain region controlling respiration in the central nervous system. Gelsenicine (1) strongly inhibited the firing of action potentials in VRG neurons through its ability to stimulate GABA_A receptors, the main receptors involved in inhibitory neurotransmission. Application of GABA_A receptor antagonists successively reversed action potential firing in gelsenicine (1)-treated VRG neurons. Importantly, the GABA_A receptor antagonists securinine and flumazenil significantly increased the survival of poisoned animals. Our findings provide insight into the components and mechanisms of G. elegans toxicity, and should assist the development of effective emergency treatments for G. elegans poisoning.

Adenomyosis is a common gynecological disease characterized by the invasion of endometrial glands and stroma into the myometrium of uterus, the pathological mechanism of which remains unclear yet. Disturbed lipid metabolism extensively affects abnormal cell proliferation and invasion in various diseases. However, the lipidome signature of human myometrium, which could be crucial in the development of adenomyosis, remains unknown. In this study, we generated the first lipidome profiling of human myometrium using a high-coverage and quantitative lipidomics approach based on ultra-performance liquid chromatography (UPLC) coupled with triple quadrupole (QqQ)-mass spectrometry (MS). A total of 317 lipid species were successfully quantified in the myometrial tissues from women with (n = 38) or without (n = 65) adenomyosis who underwent hysterectomy at Peking Union Medical College Hospital (Bejing, China). Up to 83 lipid species showed significant alternations in content between the two groups. These lipid aberrations involved multiple metabolic pathways, and emphasized inflammation, cell migration, and immune dysregulation upon adenomyosis. Moreover, receiver operating characteristic (ROC) curve analysis found that the combination of five lipid species could accurately distinguished the myometrial samples from women with and without adenomyosis with an area under the curve (AUC) of 0.906. Desorption electrospray ionization MS imaging (MSI) further underscored the heterogeneous distributions of these lipid markers in the adenomyosis lesion and adjacent myometrial tissue. Collectively, these results extremely improved our understanding on the molecular basis of adenomyosis, and could shed light on developing potential biomarkers and new therapeutic directions for adenomyosis.

Objective To analyse medication patterns for treating menstrual disorders with disharmony between the Chong and Ren pattern based on data mining.Methods Medical records from the gynecological outpatient department of Wenzhou TCM Hospital of Zhejiang Chinese Medical University from October 2023 to March 2024 were collected.A database was established based on Traditional Chinese Medicine Inheritance Computer System(V3.0),and data mining methods such as frequency statistics,association rule analysis and cluster analysis were used to analyze the medication patterns of traditional Chinese medicine in the treatment of menstrual disorders with disharmony between the Chong and Ren pattern.Results A total of 9003 effective prescriptions were collected,involving 410 Chinese medicinal herbs.The top five herbs by frequency were Danggui,Tusizi,Cuxiangfu,Xuduan,and Danshen.Tonic medicines,circulate blood and transform stasis medicines and interior heat-clearing medicines were used more frequently.The four qi were mainly warm and cold,the five lavours were mainly bitter and sweet,and the channel were mainly liver and spleen channel.By association analysis,a combination of drugs with Tusizi,Gouqizi,Danggui,Xuduan,Cuxiangfu were obtained.After cluster analysis,five groups of effective class squares were obtained.Conclusion Treatment of menstrual disorders with disharmony between the Chong and Ren pattern is used to tonic medicines,circulate blood and transform stasis medicines and interior heat-clearing medicines,pay attention to the balance of liver,spleen,kidney.The prescribing strategy considers both superficial and underlying conditions,employs a gradual rather than abrupt approach,integrates both cold and warm remedies,and ensures mutual reinforcement and restriction among the treatments.

Objective:To investigate the efficacy and safety of electric microneedling combined with recombinant collagen liquid dressing, compound glycyrrhizin tablets, and hydrocortisone butyrate ointment for the treatment of mild to moderate alopecia areata in children.Methods:This is a prospective study. A total of 72 children with mild to moderate alopecia areata, admitted to the Department of Dermatology, Zunyi Maternal and Child Health Hospital from November 2023 to June 2024, were included in this study. The children were randomly assigned to either the experimental group, which received electric microneedling combined with treatment, or the control group, which received treatment without microneedling, based on the order of their visits. All patients received oral compound glycyrrhizin tablets and topical hydrocortisone butyrate ointment for treatment. In the experimental group, electric microneedling was used to puncture the alopecia lesions while simultaneously applying recombinant collagen liquid dressing. The control group did not receive electric microneedling treatment and only had the recombinant collagen liquid dressing applied to the lesions. The treatment lasted for 12 weeks. The efficacy and incidence of adverse reactions were compared between the two groups. After treatment, all patients were followed up for 3 months to check for any recurrence of this condition.Results:There was no significant difference in response rate between the experimental and control groups [81.58% (31/38) vs. 73.53% (25/34), χ2 = 0.67, P = 0.412). No significant difference in cure rate was observed between the experimental and control groups [57.89% (22/38) vs. 47.06% (16/34), χ2= 0.85, P = 0.358]. The time to effect in the experimental group was shorter than that in the control group [(3.16 ± 0.73) weeks vs. (4.60 ± 1.08) weeks, t = 5.15, P < 0.001]. The incidence of adverse reactions did not differ significantly between the experimental and control groups [7.89% (3/38) vs. 0, Fisher value = 0.24, P = 0.242]. There was no significant difference in recurrence rate between experimental and control groups [6.45% (2/31) vs. 12.00% (3/25), χ2 = 0.06, P = 0.801). Conclusions:The combination of electric microneedling, recombinant collagen liquid dressing, compound glycyrrhizin tablets, and hydrocortisone butyrate ointment provides a rapid onset of effect and is safe and effective for the treatment of mild to moderate alopecia areata in children.

Yuejuwan is a classic formula widely used by doctors to relieve liver and depression， with precise clinical efficacy in traditional Chinese medicine （TCM）. The authors used bibliometric methods to collect and collate 495 ancient data related to Yuejuwan， and 105 valid data were screened out， involving 68 ancient Chinese medical books. After systematic verification of the origin of the formula of Yuejuwan， the main treatment symptoms， the principle of the formula， the composition of the drug， the dosage， the preparation method， the decoction method， and other information， the results showed that Yuejuwan originated from the Danxi Xinfa （《丹溪心法》） of the Yuan Dynasty by ZHU Zhenheng， and it is composed of five medicines， namely Atractylodis Rhizoma， Cyperi Rhizom， Chuanxiong Rhizoma， Massa Medicata Fermentata， and Gardeniae Fructus. In terms of drug base， Atractylodis Rhizoma， Cyperi Rhizom， Chuanxiong Rhizoma， and Gardeniae Fructus are in line with the records in the 2020 edition of Chinese Pharmacopoeia， and Massa Medicata Fermentata is used. The preparation method is as follows： Massa Medicata Fermentata and Gardeniae Fructus are fried， and Cyperi Rhizoma is roasted in vinegar. Chuanxiong Rhizoma is used in the raw form， and Atractylodis Rhizoma is prepared with rice swill. The formula can regulate Qi and relieve depression and broaden the middle and remove fullness. It is clinically used for the treatment of six types of depression syndromes， chest and diaphragm plumpness， abdominal distension and leg acid， acid swallowing and vomiting， eating and drinking disharmony， toothache， mouth and tongue sores， and other diseases. The most used dosage of the formula in the ancient records through the ages is converted into the modern dosage， namely 3.05 g Atractylodis Rhizoma， 3.05 g Cyperi Rhizoma， 3.05 g Chuanxiong Rhizoma， 3.05 g Massa Medicata Fermentata， and 3.05 g Gardeniae Fructus， and the daily dosage is 15.25 g. The converted dosage is similar to that recorded in the 2020 edition of the Chinese Pharmacopoeia. The formula is in pill form， and medicine should be taken with lukewarm boiled water after the meal. Through the excavation of the ancient literature related to Yuejuwan， the key information of the formula is identified， with a view to providing a more accurate reference for the clinical application of Yuejuwan and subsequent in-depth investigation.