ObjectiveThis study aimed to investigate the optimal compatibility ratio of the Chuanxiong Rhizoma-Carthami Flos （CR-CF） couplet medicines in ischemic stroke （IS） therapy and its pharmacological action mechanism， providing a scientific basis for the clinical application of CR-CF couplet medicines in IS therapy. MethodsThe chemical composition of CR-CF was analyzed using liquid chromatography mass spectrometry （LC-MS/MS）. The contents of eight characteristic chemical components in aqueous extracts of CR-CF with common clinical compatibility ratios （1∶1， 1∶2， 1∶3， 3∶2， 2∶1） were determined by ultra-high performance liquid chromatography（UHPLC）. An oxygen-glucose deprivation/reoxygenation （OGD/R）-induced mouse hippocampal neuron HT22 cell injury model was established， and cells were treated with different CR-CF compatibility ratios. The collaborative index （CI） was calculated by using CompuSyn software. A cerebral artery occlusion/reperfusion （MCAO/R） model of rats was induced by using the modified Longa suture method. The rats were divided into the sham group， model group， Chuanxiong Rhizoma （CR） group （1.3 g·kg^-1）， Carthami Flos （CF） group （3.9 g·kg^-1）， CR-CF group （5.2 g·kg^-1）， and edaravone group （5 mg·kg^-1）. Neuronal defect scores were assessed by the Longa scoring method. Cerebral infarction volume was measured by 2，3，5-triphenyltetrazolium chloride（TTC） staining. Neuronal damage was observed via hematoxylin-eosin （HE） staining. Neuronal apoptosis of rats was detected by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling （TUNEL） staining， and the expression of apoptosis-related proteins was analyzed by Western blot. Label-free proteomics was employed to screen differentially expressed proteins， and Western blot was used to examine the expression of phosphatidylinositol 3-kinase/protein kinase B（PI3K/Akt） signaling pathway-related proteins. Finally， molecular docking was performed to predict the binding affinity of eight active constituents in CR-CF （1∶3） with PI3K. ResultsWhen CR-CF was combined at a 1∶3 ratio， the total content of the eight active constituents in the extract was the highest， and the synergistic protective effect on OGD/R-injured HT22 cells was the strongest （CI=0.308）. Animal experiments showed that compared with the sham group， the model group exhibited increased neuroecological score points （P<0.01）， larger cerebral infarction volumes （P<0.01）， aggravated brain tissue damage， elevated neuronal apoptosis （P<0.01）， and increased B-cell lymphoma-2（Bcl-2）-associated X protein （Bax）/Bcl-2 and cleaved Cysteinyl aspartate specific proteinase-3/Cysteinyl aspartate specific proteinase-3 （cleaved Caspase-3/Caspase-3） ratios （P<0.01）. Compared with the model group， CR-CF （1∶3） significantly reduced neurological scores （P<0.01）， significantly decreased cerebral infarction volume （P<0.01）， alleviated brain tissue damage， inhibited neuronal apoptosis （P<0.01）， and significantly lowered the Bax/Bcl-2 and cleaved Caspase-3/Caspase-3 ratios （P<0.01）. The therapeutic effect of CR-CF （1∶3） was superior to that of CR or CF alone. Proteomic analysis revealed that CR-CF （1∶3） activated the PI3K/Akt signaling pathway. Validation experiments demonstrated that compared with the sham group， the model group showed obviously reduced p-PI3K/PI3K and p-Akt/Akt （P<0.05）. Compared with the model group， p-PI3K/PI3K and p-Akt/Akt ratios （P<0.05） obviously increased. Compared with the CR-CF group， the 2-（4-morpholinyl）-8-phenyl-4H-1-benzopyran-4-one LY294002 inhibitor+CR-CF group exhibited obviously decreased p-PI3K/PI3K and p-Akt/Akt （P<0.05）. Molecular docking results indicated that the active constituents of CR-CF （1∶3） had strong binding affinity with PI3K. ConclusionThe CR-CF couplet medicines at a 1∶3 ratio exhibit optimal synergistic effects， and their anti-IS mechanism is closely related to activation of the PI3K/Akt signaling pathway and inhibition of neuronal apoptosis.

ObjectiveTo observe the effect of heat-sensitive moxibustion on quality of life and immune function in non-small cell lung cancer （NSCLC） patients undergoing chemotherapy. MethodsSeventy NSCLC patients with qi deficiency and phlegm stasis syndrome were randomly divided into an intervention group and a control group， with 35 cases in each group. The control group received chemotherapy combined with routine symptomatic treatment， while the intervention group additionally received heat-sensitive moxibustion since the first day of chemotherapy. Acupoints included Dazhui （GV14）， bilateral Feishu （BL13）， Zhongwan （CV12）， Qihai （CV6）， and Guanyuan （CV4）. The site exhibiting the strongest heat-sensitization response was selected for moxibustion. Treatment was administered for 45 minutes per session， three times weekly for three consecutive weeks， totaling nine sessions. Before and after treatment， quality of life was assessed using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire （EORTC QLQ-C30）， and traditional Chinese medicine （TCM） syndrome scores were evaluated. Peripheral blood levels of natural killer （NK） cells and T-lymphocyte subsets including CD3⁺， CD4⁺， and CD8⁺， and CD4⁺/CD8⁺ ratio were measured. Levels of programmed cell death protein-1 （PD-1）， including PD-1⁺CD4⁺ and PD-1⁺CD8⁺ cells， were also assessed. Liver and renal function were monitored before and after treatment， and adverse events were recorded. ResultsIn the intervention group， 1 participant withdrew and 1 was excluded， while in the control group， 2 participants withdrew. Ultimately， 33 participants in each group were included in the final analysis. The intervention group showed significant improvements in physical， role， emotional， cognitive， and social functioning， as well as global health status after treatment， while scores for fatigue， nausea and vomiting， dyspnea， appetite loss， diarrhea， and TCM syndrome scale were significantly decreased （P＜0.05）. Moreover， the intervention group demonstrated higher scores in physical functioning， role functioning， and global health status， as well as lower scores for fatigue， nausea and vomiting， dyspnea， appetite loss， diarrhea， and the TCM syndrome scale than the control group （P＜0.05）. After treatment， the levels of peripheral NK cells and PD-1⁺CD8⁺ T cells in the intervention group increased significantly； furthermore， the intervention group exhibited higher peripheral NK cell levels and lower PD-1⁺CD8⁺ T cell levels than the control group （P＜0.05）. No significant differences were found in liver or renal function between the two groups （P＞0.05）. In addition， no adverse events such as burns or moxibustion-induced syncope occurred during the study. ConclusionHeat-sensitive moxibustion as an adjunctive therapy may enhance immune function， alleviate clinical symptoms， and improve quality of life， while demonstrating a favorable safety profile in NSCLC patients with qi deficiency and phlegm stasis.

Objective To explore the epidemiological characteristics of gouty arthritis in Northwest China from 2023 to 2025, and to formulate preventive intervention measures. Methods By retrospectively analyzing the case data of medical institutions in Northwest China from January 2023 to June 2025 (a total of 8 139 cases), the incidence trend and population distribution characteristics of gouty arthritis in this area were analyzed. Multivariate logistic regression analysis was performed to identify risk factors. Results From 2023 to 2025, the prevalence rate of gouty arthritis in adult residents in Northwest China was 3.74% (304/8 139). Among the sites affected by gouty arthritis, the metatarsophalangeal joint accounted for the highest proportion (P<0.05). From the perspective of age distribution, the prevalence rate was the highest in 40-59 years old group (5.90%), followed by 66-80 years old group (4.21%) and >80 years old group (2.75%). The incidence rate in 40-65 years old group was higher than that in the other age groups (P<0.05). High blood uric acid and creatinine, alcohol drinking, obesity, high purine diet, concurrent chronic kidney disease and metabolic syndrome were risk factors affecting gouty arthritis in Northwest China (P<0.05). Conclusion High blood uric acid level, high creatinine level, alcohol drinking, obesity, high purine diet, concurrent chronic kidney disease and metabolic syndrome are risk factors influencing gouty arthritis in Northwest China. Based on the above factors, this study proposes comprehensive prevention strategies from the individual, community and public health levels to provide a scientific basis for reducing the incidence rate of gouty arthritis.

As new evidence emerges, treatment strategies toward the functional cure of chronic hepatitis B are evolving. In 2019, a panel of national hepatologists published a Consensus Statement on the functional cure of chronic hepatitis B. Currently, an international group of hepatologists has been assembled to evaluate research since the publication of the original consensus, and to collaboratively develop the updated statements. The 2.0 Consensus was aimed to update the original consensus with the latest available studies, and provide a comprehensive overview of the current relevant scientific literatures regarding functional cure of hepatitis B, with a particular focus on issues that are not yet fully clarified. These cover the definition of functional cure of hepatitis B, its mechanisms and barriers, the effective strategies and treatment roadmap to achieve this endpoint, in particular new surrogate biomarkers used to measure efficacy or to predict response, and the appropriate approach to pursuing a functional cure in special populations, the development of emerging antivirals and immunomodulators with potential for curing hepatitis B. The statements are primarily intended to offer international guidance for clinicians in their practice to enhance the functional cure rate of chronic hepatitis B.

Gastric cancer (GC) is a globally prevalent malignancy with a particularly heavy burden in China. Helicobacter pylori ( H. pylori ) is a Group I carcinogen for GC, with a higher seroprevalence rate indicating a higher GC incidence. However, only approximately 3% of the individuals with H. pylori infection eventually develop GC, and about 2.6% still progress to GC even 10-20 years after the eradication of H. pylori . Thus, the pathogenic mechanism of H. pylori for GC must be elucidated, and high-risk individuals precisely identified. Furthermore, GC can occur even in individuals who have never been infected with H. pylori . As H. pylori infection rates decline, the proportion of H. pylori -negative GC cases is increasing annually, gaining significant research attention. In this review, potential pathogenic mechanisms of H. pylori infection are explored from the aspects of H. pylori virulence factors and host factors (genetic susceptibility and immune microenvironment). Possible risk factors for H. pylori -negative GC include infections by other microorganisms (e.g., bacteria, fungi, and viruses), autoimmune gastritis, bile reflux, genetic mutations, and environmental factors. We aim to review the potential mechanisms for GC with varying H. pylori infection statuses, identify the high-risk individuals, and pose questions that need to be addressed. In the future, as the prevalence of H. pylori infection gradually decreases, GC prevention and management must evolve to address host-specific factors and the growing challenge of H. pylori -negative GC by integrating multidisciplinary perspectives.
Stomach Neoplasms/genetics* ; Humans ; Helicobacter Infections/complications* ; Helicobacter pylori/pathogenicity* ; Risk Factors

To study the ameliorative effect of Eucommiae Cortex extract on spatial learning disabilities in APP/PS1 double-transgenic mice and explore its relationship with estrogen receptor β(ERβ)/c-Jun N-terminal kinase(JNK) signaling pathway, sixty 3-month-old male APP/PS1 mice were randomly divided into a model group, an anti-brain failure capsule group(0.585 g·kg~(-1)), a donepezil hydrochloride group(0.65 mg·kg~(-1)), and a Eucommiae Cortex extract group(1.3 g·kg~(-1)), and 15 C57BL/6 mice of the same genetic background were set as WT control group. The learning and memory ability of mice was assessed by the Morris water maze test(MWM), the passive avoidance test(PAT), and the novel object recognition test(NOR). The histomorphological and cellular ultrastructural features of the hippocampal region of the mice were observed by hematoxylin-eosin(HE) staining and transmission electron microscopy(TEM); the molecular docking validation of the key active ingredients and the key targets was performed by using AutoDock Vina software, and the immunohistochemical method(IHC) was used to detect the ERβ expression in the dentate gyrus(DG) area of mouse hippocampus. Western blot(WB) was utilized to detect the expression of ERβ, p-JNK, and JNK in mouse hippocampal area. Compared with those in the WT control group, the results of behavioral experiments showed that the latency of the mice in the model group was significantly increased, the number of platform traversals, and the target quadrant residence time were significantly decreased in the MWM. The evasion latency was significantly reduced, and the number of errors was significantly increased in the PAT. The index of recognition of novel objects was significantly reduced in the NOR. The results of HE staining indicated that the hippocampal area of mice in the model group showed a decrease in the number of neurons, disorganization of pyramidal cell arrangement, nucleus consolidation, and other changes. TEM results showed that some neuronal nuclei in the hippocampal area had a consolidated state, slightly thickened and aberrant nuclear membranes, and fewer intracytoplasmic nidus bodies; the IHC results showed that the expression of ERβ in the hippocampal DG area of the mice was reduced. The WB results showed that the ERβ expression in the hippocampal tissue was decreased, and the p-JNK/JNK level was elevated. Compared with the model group, the Eucommiae Cortex extract group showed a significant decrease in latency, and increase in number of platform traversals and target quadrant residence time in the MWM, a significant increase in evasion latency and decrease in number of errors in the PAT, and a significant increase in the index of recognition of novel objects in the NOR. In addition, there was an increase in the number of neurons in the hippocampal area of mice. The pyramidal cells tended to be arranged in an orderly manner; the nuclei of neurons in the hippocampal area were in a better state; the expression of ERβ in the hippocampal DG area of the mice was elevated; the expression of ERβ in the hippocampal tissue was elevated, and the level of p-JNK/JNK was reduced. The effects of donepezil hydrochloride group and anti-brain failure capsule on APP/PS1 mice in terms of behavioral, HE, and TEM indexes were similar to those of Eucommiae Cortex extract, and there was no significant difference between donepezil hydrochloride group and the model group in IHC and WB experiments, and the results of molecular docking indicated that the estrogen-like components in Eucommiae Cortex extract were tightly bound to ERβ. In conclusion, the binding of Eucommiae Cortex extract to estrogen receptors, regulation of ERβ expression, and activation of ERβ/JNK signaling pathway may be one of the key mechanisms by which it improves the learning and memory ability of APP/PS1 mice.
Animals ; Male ; Mice ; Mice, Transgenic ; Memory/drug effects* ; Mice, Inbred C57BL ; Estrogen Receptor beta/genetics* ; Eucommiaceae/chemistry* ; Alzheimer Disease/psychology* ; Amyloid beta-Protein Precursor/metabolism* ; Presenilin-1/metabolism* ; Humans ; MAP Kinase Signaling System/drug effects* ; Drugs, Chinese Herbal/administration & dosage* ; Hippocampus/metabolism* ; Maze Learning/drug effects* ; Learning/drug effects*

Tujia ethnic group medicine Xuetong is derived from Kadsura heteroclita, the stem of which has the medicinal value for anti-rheumatoid arthritis, liver protection, anti-tumor, anti-oxidation effects, and has been widely used in Hunan and Guangdong in China. The selection of reliable and stable reference genes is the basis for subsequent molecular research on K. heteroclita. In this study, GAPDH, TUA, Actin, UBQ, EF-1α, 18S-rRNA, CYP, UBC, TUB, H2A, and RPL were selected as candidate reference genes in Kadsura heteroclita. The gene expression levels of the 11 candidate reference genes of K. heteroclita in its 6 different parts(stem-inside of the cambium, stem-outside of the cambium, fruit, flower, root, and leaf) and under different intervention conditions [drought stress, salt stress, and methyl jasmonate(MeJA) treatment] were detected by quantitative real-time polymerase chain reaction(qRT-PCR). The expression stability of the 11 candidate reference genes was comprehensively analyzed and evaluated by geNorm, NormFinder, ΔCT algorithm, and RefFinder software. The results showed that the expression of UBC and RPL was relatively stable in 6 different parts, and UBC and GAPDH genes were relatively stable under different intervention conditions. To verify the reliability of reference genes for K. heteroclita, this study further examined the relative expression levels of KhFPS, KhIDI, KhCAS, KhSQE, KhSQS, KhSQS-2, KhHMGS, KhHMGR, KhMVD, KhMVK, KhDXR, KhDXS, KhPMVK, and KhGGPS in different parts and under different intervention conditions, which might relate to the synthesis of the main component(Xuetongsu) of K. heteroclita. The results showed that with UBC and RPL or UBC and GAPDH as the reference genes, the expression trends of these 14 genes were basically consistent in different parts or under different intervention conditions for K. heteroclita. In conclusion, UBC can be used as a reference gene of K. heteroclita for its different parts and different intervention conditions, which lays a foundation for further research on the biosynthetic pathway of main components in K. heteroclita.
Real-Time Polymerase Chain Reaction/methods* ; Reference Standards ; Gene Expression Regulation, Plant ; Gene Expression Profiling ; Plant Proteins/metabolism* ; Drugs, Chinese Herbal

PURPOSE: To analyze risk factors for severe trauma and establish a nomogram for early risk prediction, to improve the early identification of severe trauma. METHODS: This study was conducted on the patients treated in 81 trauma treatment institutions in Gansu province from 2020 to 2022. Patients were grouped by year, with 5364 patients from 2020 to 2021 as the training set and 1094 newly admitted patients in 2020 as the external validation set. Based on the injury severity score (ISS), patients in the training set were classified into 2 subgroups of the severe trauma group (n = 478, ISS scores ≥25) and the non-severe trauma group (n = 4886, ISS scores <25). Univariate and binary logistic regression analyses were employed to identify independent risk factors for severe trauma. Subsequently, a predictive model was developed using the R software environment. Furthermore, the model was subjected to internal and external validation via the Hosmer-Lemeshow test and receiver operating characteristic curve analysis. RESULTS: In total, 6458 trauma patients were included in this study. Initially, this study identified several independent risk factors for severe trauma, including multiple traumatic injuries (polytrauma), external hemorrhage, elevated shock index, elevated respiratory rate, decreased peripheral oxygen saturation, and decreased Glasgow coma scale score (all p < 0.05). For internal validation, the area under the receiver operating characteristic curve was 0.914, with the sensitivity and specificity of 88.4% and 87.6%, respectively; while for external validation, the area under the receiver operating characteristic curve was 0.936, with the sensitivity and specificity of 84.6% and 93.7%, respectively. In addition, a good model fitting was observed through the Hosmer-Lemeshow test and calibration curve analysis (p > 0.05). CONCLUSION This study establishes a nomogram for early risk prediction of severe trauma, which is suitable for primary healthcare institutions in underdeveloped western China. It facilitates early triage and quantitative assessment of trauma severity by clinicians prior to clinical interventions.
Humans ; Nomograms ; Male ; Female ; Wounds and Injuries/diagnosis* ; Risk Factors ; Middle Aged ; Adult ; Injury Severity Score ; Risk Assessment ; ROC Curve ; Aged ; Logistic Models ; China ; Glasgow Coma Scale

Nonobstructive azoospermia (NOA), one of the most severe types of male infertility, etiology often remains unclear in most cases. Therefore, this study aimed to detect four biallelic detrimental variants (0.5%) in the minichromosome maintenance domain containing 2 ( MCMDC2 ) genes in 768 NOA patients by whole-exome sequencing (WES). Hematoxylin and eosin (H&E) demonstrated that MCMDC2 deleterious variants caused meiotic arrest in three patients (c.1360G>T, c.1956G>T, and c.685C>T) and hypospermatogenesis in one patient (c.94G>T), as further confirmed through immunofluorescence (IF) staining. The single-cell RNA sequencing data indicated that MCMDC2 was substantially expressed during spermatogenesis. The variants were confirmed as deleterious and responsible for patient infertility through bioinformatics and in vitro experimental analyses. The results revealed four MCMDC2 variants related to NOA, which contributes to the current perception of the function of MCMDC2 in male fertility and presents new perspectives on the genetic etiology of NOA.
Humans ; Male ; Azoospermia/genetics* ; Meiosis/genetics* ; Spermatogenesis/genetics* ; Adult ; Exome Sequencing ; Microtubule-Associated Proteins/genetics* ; Alleles ; Infertility, Male/genetics*

OBJECTIVES: To investigate the underlying causes and clinical manifestations in infants undergoing colonoscopy, and to analyze changes in disease spectrum. METHODS: Clinical data from 180 infants who underwent a total of 184 colonoscopies at the Department of Gastroenterology, Children's Hospital Affiliated to Shandong University from January 2015 to December 2024 were retrospectively analyzed. Patients were grouped by age: ≤6 months (n=41) and >6-12 months (n=139); and by examination period: 2015-2019 (n=83) and 2020-2024 (n=97). Primary causes for performing colonoscopy, final diagnoses, and disease spectrum evolution were assessed. RESULTS: Among 184 colonoscopies, the leading causes prompting examination were hematochezia (37.8%, 68/180), diarrhea (36.7%, 66/180), and co-occurring hematochezia and diarrhea (21.1%, 38/180). Causes for performing colonoscopy differed significantly by age group (P<0.05). Colonic polyps were only detected in the >6-12 months group (P<0.05). Compared to the 2015-2019 group, the 2020-2024 group had fewer food allergy-related gastrointestinal diseases (P<0.05) but more colitis (P<0.05). CONCLUSIONS Colonoscopy is essential for diagnosing infantile digestive disorders, with disease spectra varying by age and time period.
Humans ; Infant ; Colonoscopy ; Male ; Female ; Retrospective Studies ; Infant, Newborn ; Diarrhea/etiology* ; Gastrointestinal Hemorrhage/etiology*