OBJECTIVE To investigate the effects and mechanisms of Lycium ruthenicum Murr. in improving sleep. METHODS Network pharmacology was employed to identify the active components of L. ruthenicum and their associated disease targets， followed by enrichment analysis. A caffeine‑induced zebrafish model of sleep deprivation was established ， and the zebrafish were treated with L. ruthenicum Murr. extract （LRME） at concentrations of 0.1， 0.2 and 0.4 mg/mL， respectively； 24 h later， behavioral changes of zebrafish and pathological alterations in brain neurons were subsequently observed. The levels of inflammatory factors [interleukin-6 （IL-6）， IL-1β， IL-10， tumor necrosis factor-α （TNF-α）]， oxidative stress markers [superoxide dismutase （SOD）， malondialdehyde （MDA）， glutathione peroxidase （GSH-Px）， catalase （CAT）]， and neurotransmitters [5- hydroxytryptamine （5-HT）， γ-aminobutyric acid （GABA）， glutamic acid （Glu）， dopamine （DA）， and norepinephrine （NE）] were measured. The protein expression levels of protein kinase B1 （AKT1）， phosphorylated AKT1 （p-AKT1）， epidermal growth factor receptor （EGFR）， B-cell lymphoma 2 （Bcl-2）， sarcoma proto-oncogene，non-receptor tyrosine kinase （SRC）， and heat shock protein 90α family class A member 1 （HSP90AA1） in the zebrafish were also determined. RESULTS A total of 12 active components and 176 intersecting disease targets were identified through network pharmacology analysis. Among these， apigenin， naringenin and others were recognized as core active compounds， while AKT1， EGFR and others served as key targets； EGFR tyrosine kinase inhibitor resistance signaling pathway was identified as the critical pathway. The sleep improvement rates in zebrafish of LRME low-， medium-， and high-dose groups were 54.60%， 69.03% and 77.97%， 开发。E-mail：hjp_yft@163.com respectively， while the inhibition ratios of locomotor distance were 0.57， 0.83 and 0.95， respectively. Compared with the model group， the number of resting counts， resting time and resting distance were significantly increased/extended in LRME medium- and high-dose groups （P＜0.05）. Neuronal damage in the brain was alleviated. Additionally， the levels of IL-6， IL-1β， TNF-α， MDA， Glu， DA and NE， as well as the protein expression levels of AKT1， p-AKT1， EGFR， SRC and HSP90AA1， were markedly reduced （P＜0.05）， while the levels of IL-10， SOD， GSH-Px， CAT， 5-HT and GABA， as well as Bcl-2 protein expression， were significantly elevated （P＜0.05）. CONCLUSIONS L. ruthenicum Murr. demonstrates sleep-improving effects， and its specific mechanism may be related to the regulation of inflammatory responses， oxidative stress， neurotransmitter balance， and the EGFR tyrosine kinase inhibitor resistance signaling pathway.

Environmental pollution is a significant public health challenge worldwide, and investigating the causal relationship between environmental exposure and population health outcomes is a key objective of environmental epidemiology research. In recent years, the complexity of environmental exposures has increasingly come to the forefront, making it challenging for observational studies that dominate environmental epidemiology to accurately estimate causal effects. Causal inference methods are particularly advantageous in controlling for confounding factors, thus holding great potential in environmental epidemiology research. Researchers can use appropriate causal inference methods to simulate the process of randomization, providing strong support for revealing the causal relationship between environmental exposure and health outcomes. However, there is a lack of reviews on the application of causal inference methods in environmental epidemiology studies in China. Therefore, this study introduced the basic principles of common causal inference statistical methods in environmental epidemiology, summarized the applicable conditions, advantages and disadvantages of various methods, and provided R software implementation codes for these methods, aiming to offer guidance for optimizing research design and practicing causal inference statistical methods.

Objective: To investigate the status of antibiotic exposure in third grade primary school students in Shenzhen,so as to provide evidence for the scientific management of antibiotic use and reduction of population health risks. Methods: From 1 September to 30 October 2021, 200 third grade students from 8 primary schools in Luohu District of Shenzhen were selected by cluster random sampling as research subjects. The body composition was measured, urine samples were collected, and the contents of 35 antibiotics in the samples were detected by mass spectrometry. Relevant dietary habit information of the subjects was collected via questionnaires. The Chi square test was used to compare the detection rate of antibiotics among different genders and weight grades. The Logistic regression model was adopted to evaluate the correlation between the target antibiotic detection rate and dietary habits. Results: At least one type of antibiotic was detected in 198 of the subjects with an overall detection rate of 99.0% . Among the 35 target antibiotics, 23 were detected with detection rates ranging from 0.5%-69.5%. Quinolones had the highest detection rate of 86.5% , followed by macrolides and sulfonamides with detection rates of 77.5% and 76.5%, respectively. The detection rate of antibiotics was 98.3% in boys and 100.0% in girls with no statistically significant difference ( χ 2=1.35, P >0.05). The detection rates of quinolones, macrolides, and sulfonamides varied significantly among children with different BMI categories ( χ 2=38.18, 12.45, 9.76 , all P <0.05). The multivariate Logistic regression model analysis showed that the macrolide detection rate was affected by genders( OR =0.42) and the sulfonamide detection rate was significantly correlated with the frequency of dairy product consumption and being overweight( OR =2.01)(both P <0.05). Enrofloxacin was associated with the weekly consumption frequency of livestock meat such as pork, beef and mutton, as well as the weekly consumption frequency of poultry meat such as chicken, duck and goose ( OR = 2.81,2.17,both P <0.05). Trimethoprim was associated with the weekly frequency of drinking pure milk ( OR =5.49, P < 0.05 ). Conclusions Third grade primary school students in Shenzhen are generally exposed to low dose antibiotics. Macrolides, quinolones, and sulfonamides may be associated with the risk of obesity in primary school students.

Objective To analyze Chinese and English publications pertaining to Oncomelania hupensis control from 2005 to 2024, so as to decipher the research status and hotspots of O. hupensis control. Methods Chinese and English publications pertaining to O. hupensis control from 2005 to 2024 were retrieved in the Web of Science Core Collection Database and China National Knowledge Infrastructure. The annual number of publications was analyzed from 2005 to 2024, and the author and institution cooperation networks were mapped using the software CiteSpace 6.3.1. Keywords were extracted from publications to map the co-occurrence, burst and timeline of keywords to identify the research hotspots of O. hupensis control. Results A total of 158 English publications and 771 Chinese publications were included for bibliometric analyses. The overall output of English publications was relatively small from 2005 to 2024, the annual average publication was 7.90 publications. Parasites & Vectors was the most productive journal by the number of publications (21 publications). The three most productive authors included Li Shizhu (24 publications), Zhou Xiaonong (13 publications), and Yang Kun (12 publications), and the three most productive institutions included Chinese Center for Disease Control and Prevention (49 publications), the WHO (27 publications), and Fudan University (25 publications). The annual average number of Chinese publications was high from 2005 to 2015 (57.73 publications), and reduced to 15.11 publications during the period from 2016 to 2024, with Chinese Journal of Schistosomiasis Control as the most productive journal (241 publications). The three most productive authors included Wang Wanxian (18 publications), Sun Qixiang (16 publications), and Dai Jianrong (16 publications), and the three most productive institutions included Jiangsu Institute of Parasitic Diseases (55 publications), Chinese Center for Disease Control and Prevention (47 publications), and Hubei Uni-versity (38 publications). Among the 158 English publications, molluscicidal effect, climate change, geographic information, biological control, machine learning were current research hotspots, and the Yangtze River and elimination were emerging research hotspots. Among the 771 Chinese publications, molluscicidal effect, niclosamide, comprehensive management, molluscicide, effectiveness evaluation, marshland, and endophyte were current research hotspots, and the future research hotspots shifted to molluscicidal effect and pyriclobenzuron. Conclusions Limited attention is paid to the research on O. hupensis control across the world. The Yangtze River, elimination, molluscicidal effect, and pyriclobenzuron may be future research hotspots. High attention is recommended to be paid to the research on O. hupensis control, and development of diverse approaches for O. hupensis control is of urgent needs. We should continue to attach importance to the control research of O. hupensis and strengthen the exploration of diverse snail extermination and control methods.

ObjectiveThis paper aims to investigate the differential mechanisms underlying the staged therapeutic effects of Qijia Rougan formula on liver fibrosis using proteomic technology. MethodsThe staged rat model of liver fibrosis was established by subcutaneous injection of carbon tetrachloride （CCl₄） and olive oil. One hundred and four SD rats were randomized into thirteen groups：a normal group，a two-week model group，a four-week model group，a six-week model group，an eight-week model group，a two-week Qijia Rougan formula group，a four-week Qijia Rougan formula group，a six-week Qijia Rougan formula group，an eight-week Qijia Rougan formula group，a two-week compound Biejia Ruangan tablet group，a four-week Compound Biejia Ruangan Tablet group，a six-week Compound Biejia Ruangan Tablet group，and an eight-week compound Biejia Ruangan tablet group. After two weeks of drug intervention，liver tissue and abdominal aortic blood samples were collected from the rats for testing. Hematoxylin-eosin （HE） staining，Masson staining，and Picro Sirius red staining were used to observe pathological damage and collagen fiber deposition in liver tissues. Immunohistochemistry （IHC） was employed to detect the contents of fibrosis markers in liver tissues. The contents of liver function indicators in the serum were measured using a fully automated biochemical analyzer，and the levels of liver fibrosis indicators in the serum were assessed by enzyme-linked immunosorbent assay （ELISA）. Liver tissues from the normal group，each model group，and each Qijia Rougan formula group were subjected to label-free quantitative proteomic analysis to identify differential proteins among the groups，with key proteins validated by Western blot. Finally，bioinformatics analysis was performed on the differential proteins. Results（1） The staged rat model of liver fibrosis constructed with CCl₄ and olive oil showed pathological results at the 2^nd，4^th，6^th，and 8^th weeks of modeling that were consistent with the Metavir standards for the F1，F2，F3，and F4 stages. Compared with those in the normal control group，the protein expressions of α-smooth muscle actin （α-SMA） and Collagen Ⅰ were significantly increased in each stage （P<0.05）. The levels of liver function indicators in the serum，including alanine aminotransferase （ALT），aspartate aminotransferase （AST），alkaline phosphatase （ALP），direct bilirubin （DBIL），and total bilirubin （TBil） in each model group，were significantly elevated in each stage （P<0.01）. The levels of liver fibrosis indicators in the serum，including procollagen Ⅲ peptide （PⅢP），type Ⅳ collagen（Ⅳ-C），hyaluronic acid （HA），and laminin （LN） in each model group，were significantly increased in each stage （P<0.05，P<0.01）. This study successfully established a staged rat model of liver fibrosis. （2） Compared with the model groups at each stage，the administration groups showed a reduction in hepatocyte ballooning degeneration，a more orderly arrangement of hepatocytes，and a decrease of inflammatory cell infiltration. The blue-stained collagen fibers became significantly thinner and finer，with reduced and narrowed fibrous septa. The areas of collagen fibers and Picro Sirius red staining were reduced （P<0.05）. The positive areas of α-SMA and Collagen Ⅰ expression were significantly decreased （P<0.05）. The levels of ALT，AST，ALP，DBIL，and TBil in the rats of the model groups at each stage were significantly reduced （P<0.05，P<0.01）. The levels of PⅢP，Ⅳ-C，HA，and LN in the rats of the model groups at each stage were significantly decreased （P<0.05）. Among these，the improvements in all indicators were most significant in the F3 stage （P<0.01）.（3） The proteomic results show that a total of 165 differential proteins exhibit a callback trend when comparing the model groups at four stages with the normal group，and when comparing the Qijia Rougan formula group with the model group. Western blot analysis reveals that the levels of NAD（P）H：quinone oxidoreductase 1 （NQO1），mitogen-activated protein kinase 1 （MAPK1），arginase 1 （Arg1），and glutathione S-transferase α1 （GSTA1） were consistent with the proteomic results. Bioinformatics results reveal that 165 differentially expressed proteins are enriched in multiple signaling pathways. Notably，signaling pathways such as drug metabolism-cytochrome P450，arginine biosynthesis，and the peroxisome proliferator-activated receptor （PPAR） signaling pathway were found to be closely associated with liver fibrosis，suggesting that the Qijia Rougan formula may exert its staged regulatory effects on liver fibrosis by regulating these pathways. ConclusionThe Qijia Rougan formula may achieve staged regulation of liver fibrosis by regulating drug metabolism-cytochrome P450，arginine biosynthesis，and the PPAR signaling pathway.

This article reports a rare case of autoinflammatory disease presenting initially with skin induration and swelling after trauma as the initial manifestation, followed by progressive limb weakness. The patient was a middle-aged female who developed skin induration and swelling after trauma, which gradually progressed to limb weakness, dysarthria and bilateral facial paralysis, accompanied by livedo reticularis of the lower extremities, diffuse skin induration of the limbs, and beaded subcutaneous nodules in the right upper limb. The patient had a susceptibility to infection since childhood and a history of chronic livedo reticularis. Skin pathological examination revealed panniculitis. A comprehensive etiological screening for special infections and autoimmune diseases was completed with an unremarkable results, and whole-exome sequencing showed no abnormal findings. Following a multidisciplinary discussion combined with RNA sequencing results, the patient was diagnosed with an autoinflammatory disease, with a suspected type Ⅰ interferonopathy. Treatment with tofacitinib resulted in gradual improvement of clinical symptoms. This case highlights the importance of detailed medical history collection, systematic physical examination and multidisciplinary collaborative diagnosis and treatment, and underscores the pivotal role of molecular diagnosis in the confirmation of rare diseases. It can provide a reference for the clinical diagnosis and management of similar rare cases.

Owing to its inherent advantages—such as being non-destructive, rapid, highly molecule-specific, and minimally interfered with by moisture—Raman spectroscopy has been widely adopted in the fields of skin barrier function assessment, monitoring the transdermal penetration of active cosmetic ingredients, and the identification and quality control of cosmetic products. Despite these strengths, the practical application of this technique faces a significant bottleneck: the strong fluorescence background generated by endogenous skin components and exogenous cosmetic additives. Endogenous skin substances, such as structural proteins (e.g., collagen and elastin), metabolic coenzymes (e.g., nicotinamide adenine dinucleotide), and pigments (e.g., melanin), together with exogenous cosmetic constituents like organic colorants, chemical sunscreens, and fragrances, often possess strong absorption and emission characteristics. When excited by lasers, these components produce a fluorescence background that can be 10⁶ to 10⁸ times stronger than the Raman scattering signals, effectively masking the inherently weak vibrational fingerprint information. In recent years, driven by the rapid development of optoelectronic hardware and artificial intelligence algorithms, fluorescence suppression strategies have evolved from isolated, single-method approaches into comprehensive, multi-level synergistic systems. These systems are categorized into three distinct tiers: sample preparation, signal acquisition, and data processing. At the sample preparation level, techniques such as photobleaching and surface-enhanced Raman spectroscopy (SERS) are employed to eliminate or bypass the generation of fluorescence at the source. At the signal acquisition level, instrumental improvements—including the use of long-wavelength near-infrared excitation (typically 785 nm or 1 064 nm), confocal spatial filtering, and shifted excitation Raman difference spectroscopy (SERDS)— are utilized to physically isolate Raman signals from the fluorescence background. Furthermore, at the data processing level, numerical baseline correction methods such as polynomial fitting, penalized least squares (e.g., airPLS, arPLS), wavelet transform, and derivative algorithms are increasingly integrated into the analytical pipeline to extract Raman spectral features from mixed signals without increasing hardware costs or acquisition time. This review provides a systematic categorization and critical evaluation of these fluorescence suppression methods, detailing their underlying principles, technical advantages, and inherent limitations in diverse experimental setups. By focusing on critical application scenarios—including skin barrier assessment, percutaneous absorption monitoring, the routine quality control of cosmetics, and the emerging field of portable on-site detection—this paper explores the current state of technique selection and optimization. Finally, the article discusses future development trends, emphasizing the necessity of constructing adaptive, tiered suppression strategies, developing intelligent and automated data processing algorithms, and promoting the integration of portable, multi-modal diagnostic devices. The objective of this review is to provide a comprehensive technical reference to facilitate the transition of Raman spectroscopy from a specialized laboratory tool into a routine, robust analytical platform for advancements in skin science and cosmetic research.

Objective The purpose of this study is to observe the dynamic changes of host intestinal microflora during the evolution and development of the pathogenesis of"spleen qi deficiency syndrome-spleen yin deficiency syndrome",so as to explore its possible mechanism.Methods The rat model of spleen Qi deficiency syndrome was established by exhaustive swimming and improper diet rhythm.On this basis,the rat model of spleen-yin deficiency syndrome was established by combining the method of consuming yin fluid.Immune-associated cytokines were assessed using ELISA assay and altered composition and diversity in gut microbiota were observed via 16S rRNA sequencing analysis.Results Compared with the control group,sIgA,IL-4,IL-10 and TGF-β in the small intestine of the model group decreased,while IFN-γ and IL-17 levels increased(P<0.05,P<0.01).The changes of immune-related cytokines proved that the immune function of spleen deficiency rats was low.In addition,the intestinal flora structure of rats with spleen deficiency has also changed significantly.The proportion of Firmicutes and Bacteroides changed and the abundance of Proteobacteria increased.The abundance of some probiotics like Lactobacillus and Oscillospira decreased(P<0.01,P<0.05)while some pathogens like Clostridium,SMB53,Campylobacterales,Desulfovibrionales and Enterobacteriales increased(P<0.05).The characteristic changes of intestinal flora in spleen Qi deficiency stage were the abnormal increase of Allobaculum,Bifidobacterium,Prevotella and Adlercreutzia(P<0.01),while in spleen Yin deficiency stage was characterized by a significant increase in the abundance of Ruminococcus(P<0.05).Conclusion Spleen deficiency syndrome is closely related to the changes of intestinal microflora.The abundance of probiotics in the gut microbiota of rats with spleen deficiency syndrome decreased and the abundance of pathogenic bacteria increased.The gut microbiota changes dynamically in the development of spleen deficiency syndrome,which have their own characteristics in the spleen Qi deficiency and spleen Yin deficiency stage respectively.

Objective The aim is to understand the common scenarios of non-medical use of prescription opioids(NMUPO)and analyze the potential facilitating and hindering factors in the regulatory process of NMUPO from the perspective of healthcare professionals.Methods Healthcare professionals in local hospitals were surveyed through a two-stage purposive sampling from June to August 2022 in Ningbo,China.The survey was conducted using a semi-structured questionnaire on topics,and thematic analysis were used to identify and summarise key themes and patterns.Results A total of 75 participants were included,the average age was(43.9±7.2)years,and 54(72.0%)were male.The most common NMUPO scenarios involved middle-aged males pretending acute severe pain to obtain injectable opioids.The facilitating and hindering factors related to the regulation of NMUPO can be categorized into three types:institutional governance,technical support,and individual behaviors.At the institutional level,facilitating factors included strict national prescribing policies and local"narcotic drug card"systems,while barriers comprised incomplete lists of controlled substances.At the technological support level,facilitating factors included the establishment of regional health information platforms,while barriers included the lack of standardized prescription guidelines and diagnostic decision-support tools.At the individual level,facilitating factors included the public's cautious attitude toward drug misuse,while barriers included strained doctor-patient relationships.Conclusion China still faces significant challenges in addressing NMUPO and urgently needs to improve the existing regulatory system.It is recommended that reforms be carried out in areas such as pharmaceutical control mechanisms,drug treatment and rehabilitation services,preventive health education activities,and the optimized use of health information systems.

Objective:To compare the pregnancy outcomes of surviving fetuses in monochorionic diam-niotic(MCDA)twin pregnancies after selective feticide or spontaneous single intrauterine fetal demise(sIUFD),and to explore the influencing factors of prognosis.Methods:A total of 219 cases of intra-uterine death of one fetus in MCDA twin pregnancies admitted to Peking University Third Hospital from September 2010 to August 2021 were collected.According to the mode of fetal death,they were divided into the spontaneous sIUFD group(120 cases)and the selective feticide group(99 cases).Data on the maternal conditions during pregnancy,the situation of the intrauterine-dead fetus,and pregnancy out-comes were collected for retrospective case-analysis.Results:The live-birth rates of surviving fetuses in the spontaneous sIUFD group and the selective feticide group were 85.0％and 81.8％respectively,and the total perinatal survival rates of surviving fetuses were 73.3％and 81.8％respectively,and there were no statistically significant differences.Compared with the spontaneous sIUFD group,the selective feticide group had a greater gestational week at delivery,and lower rate of preterm birth before 37 weeks,neonatal asphyxia,and early neonatal mortality.Using the gestational week at delivery as the outcome variable,Cox regression analysis showed that the mode of fetal death was not a risk factor affecting the gestational week at delivery of the surviving fetus,while gestational hypertension and the gestational week of fetal death were independent risk factors affecting the gestational week at delivery of the surviving fetus.Using preterm birth before 37 weeks,intrauterine death of the surviving fetus,and abnormal neonatal cranial ultrasound as outcome variables respectively,unconditional logistic regression analysis showed that the mode of fetal death,the gestational week of fetal death,the position of the dead fetus,and fetal complications were independent risk factors affecting the outcomes of the above-mentioned survi-ving fetuses.According to the results of the univariate analysis,the above risk factors were included in the multivariate regression analysis,and the results were the same as those of the univariate analysis.Conclusion:For MCDA twin pregnancy patients with severe twin-related complications,the prognosis of surviving fetuses after selective feticide is better.The proactive intrauterine intervention and treatment are of great significance for improving the prognosis of surviving fetuses.