ObjectiveTo evaluate the clinical efficacy and safety of Xiaozhen Formula （消疹方） in preventing skin toxicity induced by epidermal growth factor receptor inhibitors （EGFRIs） in patients with EGFR-mutant non-small cell lung cancer （NSCLC）. MethodsA randomized， double-blind， placebo-controlled， multicenter clinical study was conducted. A total of 120 patients with EGFR-mutant NSCLC from seven centers were enrolled and randomly assigned to a treatment group （60 cases） or a control group （60 cases）. On the basis of EGFRI-targeted therapy， patients in the treatment group received Xiaozhen Formula granules， whereas those in the control group received Xiaozhen Formula placebo granules， both at 10 g twice daily for 4 consecutive weeks. The primary outcomes were the grading of skin toxicity evaluated using the National Cancer Institute Common Terminology Criteria for Adverse Events （NCI-CTCAE） version 5.0 and the incidence of rash. Secondary outcomes included the time to onset and time to resolution of the highest-grade rash， the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 （EORTC QLQ-C30） scores， the Hospital Anxiety and Depression Scale （HADS） scores， and disease control rate， together with safety assessments. ResultsBased on the full analysis set （FAS）， the incidence of skin toxicity in the treatment group was 18.33% （11/60）， significantly lower than 45.00% （27/60） in the control group （P＜0.01）， with the highest severity of skin toxicity in both groups was grade 2. Among patients who developed rash， the resolution rate in the treatment group was 90.91% （10/11）， higher than that 33.33% （9/27） in the control group. The median time to resolution was 15 days （95%CI： 8-17 days） in the treatment group and it was not reached in the control group； the distribution of time to resolution differed significantly between groups （P＜0.001）. After treatment， the treatment group had higher EORTC QLQ-C30 functional scale and global health status/quality-of-life scores， and lower symptom scale， single-item scores， as well as HADS-A， and HADS-D scores than the control group （P＜0.05）. In the FAS analysis， the disease control rate （DCR） was 85.0% （51/60） in the treatment group， lower than 100.0% （60/60） in the control group （P=0.003）， whereas no significant between-group difference was observed in the per-protocol set （PPS） analysis （P=0.464）. The incidence of adverse events did not differ significantly between the two groups （P＞0.05）， and no definite safety signals related to the investigational drug were observed. ConclusionXiaozhen Formula can reduce the incidence of EGFRI-induced skin toxicity， and improve the outcome of rash regression， the patients' quality of life and psychological status in EGFR-mutant NSCLC patients.

ObjectiveTo investigate the effect and mechanism of Shuangshen Ningxin capsules （SSNX） in regulating the nuclear factor-κB （NF-κB） and mitogen-activated protein kinase （MAPK） pathways to inhibit inflammation and alleviate myocardial ischemia-reperfusion injury （MIRI） in rats. MethodsThe 45 healthy male Sprague-Dawley （SD） rats were divided into sham operation group， model group， and SSNX capsules group （90 mg·kg^-1）. The left anterior descending coronary artery was ligated to establish the MIRI model. Cardiac function was evaluated by echocardiography， and microvascular reperfusion was analyzed using contrast echocardiography. Myocardial inflammation and injury were assessed by hematoxylin and eosin （HE） staining， immunohistochemistry， and TdT-mediated dUTP nick end labeling （TUNEL）. The expression levels of cardiac inflammatory cytokines， including interleukin-1α （IL-1α）， interleukin-6 （IL-6）， and tumor necrosis factor-α （TNF-α） were detected by enzyme-linked immunosorbent assay （ELISA）. Core differentially expressed genes （DEGs） and enriched pathways were screened by transcriptome sequencing. Real-time quantitative polymerase chain reaction （Real-time PCR） and Western blot were used to verify the mRNA expression of Toll-like receptor 2 （TLR2）， chemokine （C-X-C motif） ligand 1 （CXCL1） and prostaglandin-endoperoxide synthase 2 （PTGS2）， as well as the protein expression of Caspase-3， cleaved Caspase-3， p-NF-κB/NF-κB， phosphorylated extracellular signal-regulated kinase 1/2 （p-ERK1/2/ERK1/2） and p-p38 MAPK/p38 MAPK. ResultsCompared with the sham operation group， the ejection fraction （EF）， fractional shortening （FS）， stroke volume （SV） and cardiac output （CO） of the model group were significantly decreased （P<0.01）， the peak time of myocardial perfusion was prolonged （P<0.01）， hypoxia-inducible factor （HIF）-1α and α-smooth muscle actin （SMA） expression increased （P<0.01）， the concentrations of inflammatory factors IL-1α， IL-6， TNF-α， TLR2， CXCL1 and PTGS2 increased （P<0.01）， and the expression of cleaved Caspase-3， p-NF-κB/NF-κB， p-ERK1/2/ERK1/2 and p-p38 MAPK/p38 MAPK proteins was significantly increased （P<0.01）. SSNX could improve cardiac function （P<0.05， P<0.01）， and significantly shorten the peak time of myocardial perfusion （P<0.01）. Moreover， it could also down-regulate HIF-1α and a-SMA expression （P<0.05， P<0.01）， and reduce the concentrations of IL-1α， IL-6， TNF-α （P<0.01）， and the mRNA expression of TLR2， CXCL1 and PTGS2 （P<0.01）. Additionally， SSNX inhibited the apoptosis rate （P<0.01） and significantly reduced the expression of Cleaved Caspase-3， p-NF-κB/NF-κB， p-ERK1/2/ERK1/2 and p-p38 MAPK/p38 MAPK proteins （P<0.01）. ConclusionSSNX can alleviate cardiac inflammation by regulating the NF-κB and MAPK signaling pathways， thereby effectively preventing and alleviating myocardial reperfusion injury.

ObjectiveTo observe the clinical efficacy and safety of Tangning Tongluo tablets in the treatment of nonproliferative diabetic retinopathy （DR）. MethodsFourteen research centers participated in this study， which spanned a time interval from September 2021 to May 2023. A total of 240 patients with nonproliferative DR were included and randomly assigned into an observation group （120 cases） and a control group （120 cases）. The observation group was treated with Tangning Tongluo tablets， and the control group with calcium dobesilate capsules. Both groups were treated for 24 consecutive weeks. The vision， DR progression rate， retinal microhemangioma， hemorrhage area， exudation area， glycosylated hemoglobin （HbA1c） level， and TCM syndrome score were assessed before and after treatment， and the safety was observed. ResultsThe vision changed in both groups after treatment （P<0.05）， and the observation group showed higher best corrected visual acuity （BCVA） than the control group （P<0.05）. The DR progression was slow with similar rates in the two groups. The fundus hemorrhage area and exudation area did not change significantly after treatment in both groups， while the observation group outperformed the control group in reducing the fundus hemorrhage area and exudation area. There was no significant difference in the number of microhemangiomas between the two groups before treatment. After treatment， the number of microhemangiomas decreased in both the observation group （Z=-1.437， P<0.05） and the control group （Z=-2.238， P<0.05）， and it showed no significant difference between the two groups. As the treatment time prolonged， the number of microhemangiomas gradually decreased in both groups. There was no significant difference in the HbA1c level between the two groups before treatment. After treatment， the decline in the HbA1c level showed no significant difference between the two groups. The TCM syndrome score did not have a statistically significant difference between the two groups before treatment. After treatment， neither the TCM syndrome score nor the response rate had significant difference between the two groups. With the extension of the treatment time， both groups showed amelioration of TCM syndrome compared with the baseline. ConclusionTangning Tongluo tablets are safe and effective in the treatment of nonproliferative DR， being capable of improving vision and reducing hemorrhage and exudation in the fundus.

Objective To establish a stable,reliable,and clinically relevant porcine model of endotoxin-induced acute respiratory distress syndrome(ARDS).Methods Ten 8-month-old male Bama minipigs were deeply sedated,followed by invasive mechanical ventilation and electrocardiographic monitoring.Lipopolysaccharide(LPS)was intravenously pumped at 600 μg/(kg·h)for 3 hours,then maintained at 15 μg/(kg·h)thereafter.Dynamic monitoring was performed at five time points after LPS injection(LPS 0,1,3,5,and 8 h),including arterial blood gas analysis and chest computed tomography(CT)scans.Pathological examination of lung tissues obtained via bronchoscopic biopsy(HE staining and transmission electron microscopy)was conducted.These indicators were comprehensively used to evaluate the success of the animal model.Results At 5 hours after LPS administration,8 minipigs developed symptoms such as skin cyanosis,elevated body temperature,and respiratory distress.The oxygenation index decreased to<300 mmHg.Chest CT scans showed diffuse pulmonary infiltrates.Histopathology revealed alveolar edema and hyaline membrane formation.Transmission electron microscopy demonstrated disruption of pulmonary blood-air barrier,depletion of lamellar bodies in type Ⅱ pneumocytes,inflammatory cell infiltration,and exudation of plasma proteins and fibrin.Compared with LPS 0 h,at LPS 8 h,the oxygenation index and arterial blood pH were significantly decreased(P<0.001),while blood lactic acid and serum potassium were significantly increased(P<0.05);serum calcium and base excess were significantly decreased(P<0.05),and the lung injury score based on HE-stained lung sections was significantly increased(P<0.01).Conclusion The porcine ARDS model established by continuous LPS injection can dynamically simulate the pathophysiological characteristics and typical pathological manifestations of clinical septic ARDS,making it an effective tool to study the pathogenesis,prevention,and treatment strategies of septic ARDS.

Objective To evaluate the changes in postoperative plasma β-endorphin(β-EP)levels in patients who had received perioperative electroacupuncture(EA)treatment in 10 randomized controlled trials(RCTs)and examine the impact of EA on postoperative pain.Methods This meta-analysis evaluated the changes in plasma β-EP levels and visual analog scale(VAS)12,24 and 48 hours after surgery in patients receiving perioperative EA.It also assessed the changes in plasma serotonin(5-hydroxytryptamine,5-HT)and prostaglandin E2(PGE2)levels at 24 hours postsurgery.A comprehensive search was conducted in the China National Knowledge Infrastructure(CNKI),Wanfang,Chongqing VIP database,Chinese Biomedical Database(CBM),Web of Science,and PubMed databases.RCTs on perioperative EA and β-EP published from the inception of the websites up to July 25,2023,were retrieved.Effect size aggregation,literature quality assessment,and bias analysis were performed using RevMan 5.3 software,and sensitivity analysis was conducted via R 4.3.1.Results A total of 10 RCTs involving 706 patients were included.EA in conjunction with conventional anesthesia significantly increased plasma β-EP levels at 12 hours postsurgery[standard mean difference(SMD)=2.79,95%CI(1.85,3.72),Z=5.81,P＜0.00001],24hours postsurgery[SMD=1.87,95%CI(0.9,2.83),Z=3.79,P=0.0001],and 48 hours postsurgery[SMD=2.02,95%CI(1.49,2.54),Z=7.50,P＜0.00001].EA reduced plasma PGE2 levels at 24 hours postsurgery and plasma 5-HT levels at 24 hours postsurgery,and the VAS at 12,24 and 48 hours after surgery also decreased.Conclusion These findings suggest that perioperative EA markedly elevates plasma β-EP levels,reduces pain-inducing factors in plasma,and effectively alleviates acute postoperative pain.

A scoping review was performed to systematically search and summarize the clinical research in the treatment of dysmenorrhea with oral Chinese patent medicines. The oral Chinese patent medicines for treating dysmenorrhea in three major drug lists, guidelines, and textbooks were screened, and the relevant clinical trials were retrieved from eight Chinese and English databases. The key information of the included trials was extracted and visually analyzed. A total of 50 Chinese patent medicines were included, among which oral Chinese patent medicines for the dysmenorrhea patients with the syndrome of Qi stagnation and blood stasis accounted for the highest proportion, and the average daily cost varied greatly among Chinese patent medicines. A total of 150 articles were included, involving 22 Chinese patent medicines, among which Guizhi Fuling Capsules/Pills, Sanjie Zhentong Capsules, and Dan'e Fukang Soft Extract were the most frequently studied. These articles mainly reported randomized controlled trial(RCT), which mainly focused on the comparison of the intervention effect between Chinese patent medicines combined with western medicine and western medicine alone, and the sample size was generally 51-100 cases. The high-frequency outcome indicators belonged to nine domains such as effective rate, adverse reactions, and laboratory examinations. This study showed that oral Chinese patent medicines had advantages in the treatment of dysmenorrhea, and the annual number of related clinical trials showed an overall growing trend. However, there were still problems such as insufficient safety information and vague description of traditional Chinese medicine(TCM) syndromes types in the instructions of Chinese patent medicines. The available clinical research had shortcomings such as uneven distribution of Chinese patent medicines, limited research scale, poor methodological rigor, and insufficient standardization of outcome indicators. In the future, it is necessary to deepen the development of high-quality clinical research and improve the contents of the instructions to ensure the effectiveness and safety of the clinical application of oral Chinese patent medicines in the treatment of dysmenorrhea.
Dysmenorrhea/drug therapy* ; Humans ; Drugs, Chinese Herbal/administration & dosage* ; Female ; Administration, Oral ; Nonprescription Drugs/administration & dosage*

This study aims to systematically review and evaluate the quality of clinical research on the treatment of adenomyosis(AM) with traditional Chinese medicine(TCM) in recent ten years, using evidence graphs. Computer searches were conducted on eight Chinese and English databases, commonly used guideline databases, and guideline-related websites, covering the period from January 1, 2014, to October 1, 2024. Two researchers independently screened, extracted information, and evaluated the quality of the evidence. The distribution and quality of the clinical research evidence were presented using both text and charts. A total of 565 articles were included in the study, comprising 523 intervention studies, 23 observational studies, 18 systematic reviews/Meta-analysis, and 1 guideline. The overall publication volume has shown a downward trend in past two years. The sample sizes of the intervention and observational studies primarily focused on 60 to 120 cases. The intervention schemes mainly involved multi-therapy combinations, including 33 classic prescriptions and 25 Chinese patent medicines. Among these, 48 studies related to 17 classic prescriptions and 45 studies related to 10 types of Chinese patent medicines involved TCM syndrome types. Randomized controlled trial(RCT) tended to focus on overall clinical efficacy and the degree of dysmenorrhea as key outcome measures. Methodological quality issues were found in 97 RCTs related to TCM decoctions and 131 RCTs related to Chinese patent medicines, primarily involving unclear explanations of some information. The AMSTAR scores for the 18 systematic reviews/Meta-analysis ranged from 1 to 8 points, with 16 studies suggesting "evidence of potential therapeutic efficacy". The recommended level for the one included guideline was B-level. TCM shows significant advantages in treating AM. Future clinical research should further standardize study designs, reference relevant reporting guidelines, improve the quality of clinical research, generate higher-level evidence-based results, and promote the high-quality development of clinical research on TCM for treating AM.
Humans ; Adenomyosis/drug therapy* ; Drugs, Chinese Herbal/therapeutic use* ; Female ; Medicine, Chinese Traditional ; Randomized Controlled Trials as Topic

Alzheimer’s disease (AD) is a chronic, progressive, and irreversible neurodegenerative disorder that typically begins with a subtle onset and progresses slowly. Pathologically, it is characterized by two hallmark features: the extracellular accumulation of amyloid β-protein (Aβ), forming senile plaques, and the intracellular hyperphosphorylation of tau protein, resulting in neurofibrillary tangles (NFTs). These pathological changes are accompanied by substantial neuronal and synaptic loss, particularly in critical brain regions such as the cerebral cortex and hippocampus. Clinically, AD presents as a gradual decline in memory, language abilities, and spatial orientation, significantly impairing the quality of life of affected individuals. With the aging population steadily increasing in China, the incidence of AD is rising, making it a major public health concern that requires urgent attention. The growing societal and economic burden of AD underscores the pressing need to identify effective diagnostic biomarkers and develop novel therapeutic strategies. Among the various molecular signaling pathways involved in neurological disorders, the Notch signaling pathway is especially noteworthy due to its evolutionary conservation and regulatory roles in cell proliferation, differentiation, development, and apoptosis. In the central nervous system, Notch signaling is essential for neurodevelopment and synaptic plasticity and has been implicated in several neurodegenerative processes. Although some studies suggest that Notch signaling may influence AD-related pathology, its precise role in AD remains poorly understood. In particular, the interaction between Notch signaling and non-coding RNAs (ncRNAs)—key regulators of gene expression—has received limited attention. NcRNAs, including long non-coding RNAs (lncRNAs) and microRNAs (miRNAs), are known to exert extensive regulatory functions at both transcriptional and post-transcriptional levels. Dysregulation of these molecules has been widely associated with various diseases, including cancers, cardiovascular conditions, and neurodegenerative disorders. Notably, interactions between ncRNAs and major signaling pathways such as Notch can produce widespread biological effects. While such interactions have been increasingly reported in several disease models, comprehensive studies investigating the regulatory relationship between Notch signaling and ncRNAs in the context of AD remain scarce. Given the capacity of ncRNAs to modulate signaling cascades and form complex regulatory networks, a deeper understanding of their crosstalk with the Notch pathway could provide novel insights into AD pathogenesis and reveal potential targets for diagnosis and treatment. In this study, we investigated the regulatory landscape involving the Notch signaling pathway and associated ncRNAs in AD using bioinformatics approaches. By integrating data from multiple public databases, we systematically identified significantly dysregulated Notch pathway-related genes and their interacting ncRNAs in AD. Based on this analysis, we constructed a lncRNA-miRNA-mRNA regulatory network to elucidate the potential mechanisms linking Notch signaling to ncRNA-mediated gene regulation in AD pathogenesis. Furthermore, we explored the internal relationships and molecular mechanisms within this network and assessed the feasibility and clinical relevance of these molecules as early diagnostic biomarkers and potential therapeutic targets for AD. This study aims to deepen our understanding of the molecular basis of AD and offer novel strategies for its diagnosis and treatment.

Objective:To investigate the impact of ginseng alcohol extract(GEE)on improving sleep quality in the aged Drosophila model by regulating the redox balance,and to elucidate its associated mechanism.Methods:Thirty-two male drosophila melanogaster(7-days-old)were randomly selected as young group,while 64 male Drosophila melanogaster flies(35-days-old)were randomly assigned to aged model group(n=32)and GEE group(n=32).The sleep parameters,including total sleep duration,daytime sleep duration,night sleep duration,0-4 h of sleep duration after lights off(ZT0-4 sleep duration),deep sleep duration,sleep episodetimes,sleep fragmentation,and the activity parameters such as the total number of locomotor activity daytime locomotor activity amount and nighttime locomotor activity amount were analyzed using the DAM2 Drosophila behavioral analysis system 7 d after administration.The grouping of the drosophila was as above,and there were 100 drosophila ineach group.The differentially expressed proteins in drosophila brain tissue were screened,identified,and functionally analyzed using two-dimensional fluorescence difference gel electrophoresis(2D-DIGE)and matrix-assisted laser desorption/ionization time of flight mass spectrometry(MALDI-TOF/TOF-MS)proteomic methods.The grouping of the drosophila was as above,and there were 100 drosophila in each group.The activities of superoxide dismutase(SOD),catalase(CAT),and glutathione peroxidase(GSH-Px)and the levels of lipid peroxidation product(MDA)in brain tissue of the drosophila were determined using assay kits.Results:Compared with young group,the total sleep duration daytime sleep duration and night sleep cluration of the drosophila in agaed group were decreased(P<0.05 or P<0.01);and the sleep rhythm amplitude was shortened.Compared with aged group,the total sleep duration and daytime and nighttime sleep durations of the drosphila in GEE group were lengthened(P<0.01).Compared with young group,the ZT0-4 sleep duration deep sleep duration and sleep fragment of the drosophila in aged group were decreased(P<0.05 or P<0.01),and the sleep rhythm amplitude was shortened.Compared with young group,the ZT0-4 sleep duration,deep sleep duration,and single sleep fragment of the drosphila in GEE group were significantly prolonged(P<0.01),and the sleep amplitude was increased.Compared with young group,there was no significant difference in diurnal spontaneous activity or total spontaneous activity of the drosophila in aged group(P>0.05),while the nocturnal spontaneous activity was significantly increased(P<0.05).Compared with aged group,the diurnal spontaneous activity,nocturnal spontaneous activity,and total spontaneous activity of the drosophila in GEE group were significantly decreased(P<0.05 or P<0.01).A total of 47 differentially expressed proteins were selected in the 2D-DIGE electrophoretic mapping.Compared with young group,the expressions of 47 differentially expressed protein sites in aged group were down-regulated mainly including glutathione S-transferase,peroxiredoxin 1 and dihydrolipoic dehydrogenase,which were related to redox balance.Compared with young group,the activities of SOD,CAT and GSH-Px in brain tissue of the drosophila in aged group were decreased(P<0.05 or P<0.01),and the level of MDA was increased(P<0.01);compared with aged group,the activities of SOD,CAT and GSH-Px in brain tissue of the drosphila in GEE group were increased(P<0.05 or P<0.01),and the MDA level was decreased(P<0.05).Conclusion:GEE has improvement effect on the sleep quality of aged drosophila,and its possible mechanism may be related to upregulating the activities of antioxidant enzymes,inhibiting the accumulation of lipid peroxidation products,and maintaining redox balance.

Scanning electrochemical microscopy(SECM)is an advanced characterization technique with high spatiotemporal resolution and plays an important role in the field of electrochemical analysis and imaging.Its applications have been extended to multiple fields,including materials science,biomedical science,and electrochemical energy storage.In recent years,Chinese research teams have made a series of progress in the field of SECM technology,mainly focusing on the optimization of instrument accuracy,innovation of working modes,improvement of imaging quality,and the integration of multiple technologies.These studies have significantly enhanced the technical performance of SECM and expanded its application scope,providing technical support for research in related fields.This article provided a systematic overview of representative achievements in the development of SECM technology in China,focusing on the improvement and design of instrument hardware,strategic optimization of working modes,intelligent upgrading of digital image algorithms,and the collaborative combination of multiple characterization techniques.On this basis,the key scientific issues and technological bottlenecks that currently constrained the development of SECM technology were discussed,and the future development trends were prospected.