ObjectiveBased on ultra-high performance liquid chromatography-quadrupole-time-of-flight mass spectrometry（UPLC-Q-TOF-MS/MS）， network pharmacology and molecular docking techniques， to explore the pharmacodynamic material basis and mechanism of Renshen Wuweizi Tang in treating spleen-lung Qi deficiency syndrome. MethodsThe chemical components in the decoction of Renshen Wuweizi Tang were systematically characterized and identified by UPLC-Q-TOF-MS/MS， and network pharmacology was used to screen potential active ingredients， collect component targets and gene sets related to spleen-lung Qi deficiency syndrome， and obtain protein interaction relationships through STRING. Cytoscape 3.9.1 was used to construct a "formula-syndrome" association network and calculate topological feature values. Gene ontology（GO） function and Kyoto Encyclopedia of Genes and Genomes（KEGG） pathway enrichment analysis were performed on core genes to explore potential pharmacodynamic links， the average shortest path between the formula-drug target network and the pharmacodynamic link gene network was calculated to discover dominant pharmacodynamic links， and MCODE plugin was used to identify core gene clusters from the dominant pharmacodynamic links， which were validated using Gene Expression Omnibus（GEO）， and molecular docking was performed between key components and core targets. ResultsOne hundred and thirty-seven components were identified in the negative ion mode， and eighty components were identified in the positive ion mode. After deduplication， a total of 185 components were identified， mainly composed of triterpenoid saponins（49） and flavonoids（54）. Based on the "formula-syndrome" correlation network analysis， energy metabolism was determined to be the dominant pharmacodynamic link of Renshen Wuweizi Tang in the treatment of spleen-lung Qi deficiency syndrome. The results of molecular docking showed that 7 components（adenosine， atractylenolide Ⅱ， atractylenolide Ⅲ， ginsenoside Rg₁， glycyrrhizin B₂， glycyrrhizin E₂ and campesterol） from 4 medicinal materials（Ginseng Radix et Rhizoma， Atractylodis Macrocephalae Rhizoma， Glycyrrhizae Radix et Rhizoma and Poria） in this formula might regulate energy metabolism by acting on 6 targets， namely cyclic adenosine monophosphate-response element binding protein 1（CREB1）， glyceraldehyde-3-phosphate dehydrogenase（GAPDH）， interleukin（IL）-6， nuclear transcription factor（NF）-κB1， peroxisome proliferator-activated receptor α（PPARα）， and tumor necrosis factor（TNF）， thus improving the symptoms of diseases related to spleen-lung Qi deficiency syndrome. ConclusionThis study established a UPLC-Q-TOF-MS/MS for rapid characterization and identification of chemical components in the decoction of Renshen Wuweizi Tang， expanding the understanding of the material composition of this formula， and found that 7 components might act on the key advantageous pharmacodynamic link "energy metabolism" through 6 targets to improve the related symptoms of spleen-lung Qi deficiency syndrome. This can provide a reference for the subsequent exploration of the material benchmark and mechanism of the famous classical formula.

With the widespread use of antibiotics, drug-resistant bacterial infections have become a significant threat to human health. Finding new antibacterial strategies that can effectively control drug-resistant bacterial infections has become an urgent task. Unlike small molecule drugs that target bacterial proteins, antisense oligonucleotide (ASO) can target genes related to bacterial resistance, pathogenesis, growth, reproduction and biofilm formation. By regulating the expression of these genes, ASO can inhibit or kill bacteria, providing a novel approach for the development of antibacterial drugs. To overcome the challenge of delivering antisense oligonucleotide into bacterial cells, various drug delivery systems have been applied in this field, including cell-penetrating peptides, lipid nanoparticles and inorganic nanoparticles, which have injected new momentum into the development of antisense oligonucleotide in the antibacterial realm. This review summarizes the current development of small nucleic acid drugs, the antibacterial mechanisms, targets, sequences and delivery vectors of antisense oligonucleotide, providing a reference for the research and development of antisense oligonucleotide in the treatment of bacterial infections.

Due to patient compliance and convenience, oral medication is likely the most common and acceptable method of drug administration. However, traditional dosage forms such as tablets or capsules may lead to low drug bioavailability and poor therapeutic efficiency. Therefore, with advancements in material science and micro/nano manufacturing technology, various carriers have been developed to enhance drug absorption in the gastrointestinal tract. In this context, we initially discuss the key biological factors that hinder drug transport and absorption (including anatomical, physical, and biological factors). Building on this foundation, recent progress in both conventional and innovative oral drug delivery routes aimed at improving drug bioavailability and targeting is reviewed. Finally, we explore future prospects for oral drug delivery systems as well as potential challenges in clinical translation.

Idiopathic pulmonary fibrosis （IPF） can be classified as pulmonary collateral disease，and its pathogenesis is mainly characterized by the loss of Qi meridian nourishment，the loss of Yin meridian nourishment，and the formation of blood stasis in the blood vessels. Qi Yin deficiency is the pathological basis that runs through IPF，and obstruction of meridians and collaterals is a key element in the development of the disease. The dysfunction of "spleen being in charge of the defensive function" is closely related to the formation of the pathological pattern of "lung deficiency and collateral stasis" in IPF. The term "spleen being in charge of the defensive function" originated from the Yellow Emperor's Inner Canon. If the spleen is healthy，the Qi will be filled with vitality. Positive energy is stored inside，evil cannot be dried up. Its concept is quite similar to the immune defense function in modern medicine. If the principle of "spleen being in charge of the defensive function" is lost，the key structure and function of the IPF alveolar epithelial barrier may be abnormal，and it can interact with various innate immune cells to promote inflammation and fibrosis processes. Therefore，this article explains the imbalance of immune homeostasis in IPF alveolar epithelium from two aspects：the barrier function of alveolar epithelial cells（AECs） and their interaction with innate immune cells. And based on the theory of "spleen being in charge of the defensive function"，using traditional Chinese medicine for strengthening the spleen and nourishing Qi to treat IPF from the perspective of the spleen. This not only strengthens the scientific connotation of "spleen being in charge of the defensive function" in the pathogenesis of IPF，but also provides new research directions and ideas for its future clinical prevention and treatment.

ObjectiveTo investigate the mechanism by which Anmeidan improves learning and memory in insomnia rats by regulating the cyclic guanosine monophosphate-adenosine monophosphate synthase （cGAS）/stimulator of interferon genes （STING） signaling pathway to influence immunoinflammation. MethodsSixty SD rats were randomly divided into a blank group， a model group， a suvorexant group （30 mg·kg^-1）， and Anmeidan low-， medium-， and high-dose groups （4.55， 9.09， and 18.18 g·kg^-1）， with 10 rats in each group. The insomnia rat model was induced by intraperitoneal injection of p-chlorophenylalanine （PCPA）. Anmeidan decoction and normal saline were administered by gavage for 28 days at the corresponding doses. Morris water maze and new object recognition tests were used to assess learning and memory functions. Hematoxylin-eosin （HE） staining and Nissl staining were performed to observe hippocampal cell morphology. Enzyme-linked immunosorbent assay （ELISA） was used to measure the serum levels of interleukin-1 （IL-1）， interleukin-1β （IL-1β）， interleukin-6 （IL-6）， interleukin-8 （IL-8）， interleukin-12 （IL-12）， interleukin-18 （IL-18）， and tumor necrosis factor-α （TNF-α）. Western blot and Real-time quantitative polymerase chain reaction（Real-time PCR） were used to detect the relative protein and mRNA expression levels of hippocampal cGAS and STING. ResultsCompared with the blank group， the 5-HT content in the model group was significantly reduced （P<0.01）. The latency to the upper platform and total distance were significantly increased （P<0.05， P<0.01）， while the residence time in the target quadrant and the number of platform crossings were significantly reduced （P<0.01）， and the relative recognition index for new objects was significantly lower （P<0.01）. The morphology and arrangement of hippocampal neurons were loose and disordered， with a decreased number of intracellular Nissl bodies. The relative expression levels of IL-1， IL-1β， IL-6， IL-8， IL-12， IL-18， TNF-α， cGAS， and STING pathway proteins and mRNA were significantly upregulated （P<0.01）. Compared with the model group， the latency to the upper platform in the high-dose Anmeidan group was significantly shortened （P<0.05）. In the medium- and high-dose Anmeidan groups and the suvorexant group， the residence time in the target quadrant and the number of platform crossings were significantly increased （P<0.01）. The total distance traveled was significantly reduced （P<0.01）， and the relative recognition index for new objects was significantly increased （P<0.01）. The hippocampal neurons were more neatly arranged， and the number of intracellular Nissl bodies increased. The expression of IL-1， IL-1β， IL-6， IL-8， IL-12， IL-18， TNF-α， and cGAS proteins and mRNA in the medium- and high-dose Anmeidan groups was significantly downregulated （P<0.05， P<0.01）. ConclusionAnmeidan improves learning and memory in insomnia rats， possibly by suppressing immunoinflammation through inhibition of the cGAS/STING signaling pathway.

ObjectiveTo elucidate the potential mechanisms by which the classic prescription Anmeidan alleviates cognitive impairment in insomnia model rats through metabolic profiling. MethodsA total of 60 SD rats were randomly divided into six groups： blank group， model group， low-， medium-， and high-dose Anmeidan groups， and the Suvorexant group， with 10 rats in each group. Except for the blank group， the insomnia model was established in all other groups via intraperitoneal injection of para-chlorophenylalanine. The Suvorexant group was administered Suvorexant solution （30 mg·kg^-1·d^-1） by gavage， while the low-， medium-， and high-dose Anmeidan groups received Anmeidan decoction （4.55， 9.09， 18.18 g·kg^-1·d^-1） by gavage. The blank group received an equivalent volume of normal saline. The open field test was used to assess spatial exploration and anxiety/depressive-like behaviors in rats. Serum levels of epidermal growth factor （EGF）， brain-derived neurotrophic factor （BDNF）， and vasoactive intestinal peptide （VIP） were measured using enzyme-linked immunosorbent assay （ELISA）. Untargeted metabolomics was employed to identify differential metabolites in rat serum， and systematic biological methods were applied to analyze the potential targets and pathways of Anmeidan. ResultsCompared to the blank group， the model group exhibited significant reductions in total distance traveled， average speed， number of entries into the central area， time spent in the central area， and frequency of upright events （P<0.01）， along with significant decreases in VIP， EGF， and BDNF levels （P<0.05，P<0.01）. A total of 100 differential metabolites were identified between the model and blank groups. Compared to the model group， the low-， medium-， and high-dose Anmeidan groups showed significant increases in total distance traveled， average speed， number of entries into the central area， time spent in the central area， and frequency of upright events （P<0.05，P<0.01）， as well as a significant increase in VIP levels （P<0.05，P<0.01）. Anmeidan significantly reversed abnormal changes in 67 metabolites compared to the model group. A combined analysis identified 134 potential targets of Anmeidan， with network topology analysis suggesting that Caspase-3， B-cell lymphoma 2 （Bcl-2）， nuclear transcription factor-κB （NF-κB）， interleukin-1β （IL-1β）， interleukin-2 （IL-2）， matrix metalloproteinase-9 （MMP-9）， and Toll-like receptor 4 （TLR4）， among others， may serve as key targets of Anmeidan. Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway analysis revealed major enriched pathways， including the cyclic adenosine monophosphate （cAMP） signaling pathway， hypoxia inducible factor-1 （HIF-1） signaling pathway， and IL-17 signaling pathway. ConclusionThis study demonstrates that Anmeidan can recalibrate abnormal metabolic profiles in insomnia model rats to mitigate cognitive impairment， with its mechanisms of action potentially involving the regulation of immune-inflammatory responses， energy metabolism， and apoptosis-related pathways.

Sleep， skin， and health are closely interconnected. Clinically， insomnia has a high incidence and is often accompanied by or secondary to skin aging. The two conditions exhibit "different diseases with the same syndrome"， significantly affecting the physical and mental health of the Chinese population. Preventing and treating skin aging by improving insomnia is an important strategy， with the principle of "treating different diseases with the same approach" serving as a crucial therapeutic guideline. However， effective clinical prevention and treatment methods for both conditions remain lacking. Traditional Chinese medicine （TCM） has a profound theoretical foundation and notable efficacy in the concurrent treatment of insomnia and skin aging， yet there are few reports on the etiology， pathogenesis， therapeutic principles， and treatment methods of their shared treatment， warranting further exploration. Based on holistic view and syndrome differentiation and treatment in TCM， this study systematically investigates the theoretical origins of the shared manifestations of insomnia and skin aging from multiple dimensions， including etiology， pathological location， pathogenesis， disease nature， and prevention and treatment strategies. As early as Huangdi's Internal Classic （Huangdi Neijing）， it was recognized that mental clarity during the day， sound sleep at night， and firm， healthy skin are key indicators of external health， whereas daytime lethargy， poor sleep quality， and dry， withered skin are prominent signs of aging. Maintaining mental clarity during the day and restful sleep at night is essential for skin integrity and healthy aging. Later medical scholars proposed that the common etiology of insomnia and skin aging lies in "internal-external interactions"， with the pathological location involving "the five organ systems". The primary pathogenesis includes "deficiency， fire， stagnation， phlegm， and blood stasis"， while the disease nature is often characterized by "a combination of deficiency and excess". Treatment should be guided by syndrome differentiation， following the principle of balancing Yin and Yang. This theoretical exploration enriches and advances TCM understanding of disease onset and prevention， providing theoretical guidance for the clinical prevention and treatment of insomnia-associated skin aging and contributing to the realization of the "Healthy China" initiative.

ObjectiveTo compare the hepatic bile acid profile between a mouse model of metabolic-associated steatohepatitis （MASH） induced by a high-fat， high-sugar， and high-cholesterol diet combined with intraperitoneal injection of 10% carbon tetrachloride （CCl₄） and MASH cases in clinical practice， and to investigate the feasibility of this model in studying drug interventions on bile acid profile in MASH. MethodsA total of 30 male C57BL/6J mice were randomly divided into control group and model group， with 15 mice in each group. The mice in the control group were given normal diet and drinking water and weekly injections of olive oil， and those in the model group were given a high-fat， high-sugar， and high-cholesterol diet， high-sugar drinking water， and weekly injections of CCl₄+olive oil. At the end of weeks 8， 12， and 16， 5 mice were selected from each group to collect samples. Behavioral assessments were performed， and body weight and liver wet weight were measured； liver pathology and lipid deposition were evaluated by HE staining， SAF scoring， oil Red O staining， the semi-quantitative analysis of stained area， the serum levels of alanine aminotransferase （ALT） and aspartate aminotransferase （AST）， and liver triglyceride （TG） content； Sirius Red staining was performed for liver tissue to assess liver fibrosis； ultra-performance liquid chromatography-tandem mass spectrometry and targeted metabolomics were used to measure the hepatic bile acid profile， including cholic acid （CA）， glycocholic acid （GCA）， chenodeoxycholic acid （CDCA）， glycochenodeoxycholic acid （GCDCA）， ursodeoxycholic acid （UDCA）， tauroursodeoxycholic acid （TUDCA）， hyodeoxycholic acid （HDCA）， and glycodeoxycholic acid （GDCA）. The independent-samples t test was used for comparison of normally distributed continuous data between two groups， and the Wilcoxon rank-sum test was used for comparison of non-normally distributed continuous data between two groups. ResultsCompared with the control group at the same time point， the model group had disheveled and dull fur， reduced activity， and relatively slow reactions at weeks 8， 12， and 16， as well as significant increases in liver wet weight （P<0.05）， the serum level of ALT （P<0.05）， the content of TG in the liver （P<0.05）， and SAF score （P<0.05）. As for the differentially expressed bile acids in liver tissue， compared with the control group at week 8， the model group had significantly higher levels of CA and CDCA and significantly lower levels of UDCA， TUDCA， HDCA， and GDCA （all P<0.05）； compared with the control group at week 12， the model group had significantly higher levels of CA， GCA， CDCA， and GCDCA and significantly lower levels of UDCA and HDCA （all P<0.05）； compared with the control group at week 16， the model group had significantly higher levels of CA， GCA， CDCA， GCDCA， and TUDCA and significantly lower levels of UDCA， HDCA， and GDCA （all P<0.05）. As for the differentially expressed bile acids in the bile acid pool of liver tissue， compared with the control group at week 8， the model group had significantly higher levels of CA and CDCA and significantly lower levels of UDCA， TUDCA， GDCA， and HDCA （all P<0.05）； compared with the control group at weeks 12 and 16， the model group had significantly higher levels of GCA and GCDCA and significantly lower levels of UDCA， GDCA， and HDCA （all P<0.05）. ConclusionThere are significant changes in the hepatic bile acid profile in a mouse model of MASH induced by a high-fat， high-sugar， and high-cholesterol diet combined with CCl₄， which are similar to the changes in bile acids in MASH cases in clinical practice， suggesting that this model can be used to explore the interventional effect of drugs on the bile acid profile in MASH.

AIM:To analyze the characteristics and correlation of phacoemulsification parameters and anterior segment parameters in cataract patients with different blood glucose levels.METHODS:A total of 45 type 2 diabetic cataract patients(45 eyes)treated in our hospital from March 2023 to April 2024 were stratified into two groups based on glycosylated hemoglobin(HbA1c)levels: group A: HbA1c <7%(n=18)and group B: 7%≤HbA1c<8.5%(n=27); a total of 94 age-matched age-related cataract patients(94 eyes)were enrolled as the control group(group C). All underwent phacoemulsification with intraocular lens implantation. Anterior segment parameters, including corneal, lens and anterior chamber measurements, were recorded. Correlations between phacoemulsification parameters and anterior segment parameters were analyzed, and differences among groups were compared.RESULTS: In groups A and B, effective phacoemulsification time(EPT)negatively correlated with corneal endothelial cell density(CECD)(r=-0.315, P=0.035). Average phacoemulsification time(APT)positively correlated with the anterior corneal surface radius of curvature(Rm; r=0.402, P=0.006)and negatively correlated with the flat axis meridian curvature(K1), steep axis meridian curvature(K2), mean curvature(Km)of the anterior corneal surface, and lens density at 6 mm zones(PDZ3; all P<0.05). Average phacoemulsification energy(AVE)positively correlated with mean lens density(LD-mean), lens density at 2 mm zones(PDZ1), lens density at 4 mm zones(PDZ2), and PDZ3(all P<0.05), and negatively with pupil diameter(r=-0.385, P=0.009). In the group C, EPT showed a positive correlation with Pentacam nucleus staging(PNS)density grade, PDZ1, PDZ2, and PDZ3(all P<0.05). A positive correlation was observed between AVE and PNS classification(r=0.246, P=0.018). Conversely, AVE exhibited a negative correlation with CECD(r=-0.245, P=0.018). EPT in groups A and B was higher than that in the group C(P<0.05). Both EPT and APT in the group B were higher than those in the group A(P<0.05). In diabetic cataract patients, CECD, corneal density(CD), and posterior corneal surface height positively correlated with diabetes duration(P<0.05). Posterior corneal surface K1 and Rm positively correlated with 7%≤HbA1c<8.5%(P<0.05). Total corneal astigmatism negatively correlated with HbA1c, 2-hour post-breakfast blood glucose(2hPBG), and fasting insulin(FINS; P<0.05). CD and lens thickness(LT)positively correlated with FINS(P<0.05).CONCLUSION: Phacoemulsification parameters and blood glucose-related indices exhibited varying degrees of correlation with anterior segment parameters in cataract patients with different blood glucose levels. EPT in diabetic cataract patients was higher than that in age-related cataract patients, while EPT and APT in diabetic cataract patients with poor glycemic control were higher than those with good glycemic control.

Objective: To investigate the indoor fine particulate matter (PM 2.5 ) pollution and its influencing factors in children s bedrooms using solid fuel, so as to provide evidence for effective strategy to reduce PM 2.5 pollution. Methods: From December 2019 to November 2020, 198 households (108 in the north, 90 in the south) from two pilots in the north(Jiamusi in Heilongjiang Province) and south of China (Mianyang in Sichuan Province) were selected, and status of solid fuels using were obtained through home visits, dynamic changes in PM 2.5 concentrations in children s bedrooms were monitored by using real time online instruments, and the influencing factors of PM 2.5 pollution were analyzed by using a mixed effects model. Results: During the monitoring period, the daily PM 2.5 concentrations in the northern and southern pilot were 78.33 (40.50, 154.80) and 38.54(26.20, 58.46) μg/m 3, respectively, exceeding standard rates of 44.57% and 33.22%. During the heating period, the daily PM 2.5 concentrations in the northern and southern pilot were 212.50(133.60,244.10) and 104.42(73.97, 134.90) μg/m 3, respectively, with over standard rates of 96.75% and 86.96%. The mixed effects model analysis results showed that children s bedroom PM 2.5 concentrations were associated with solid fuel usage duration, window opening time, room layout (shared entrance door between kitchen and bedroom), indoor smoking, indoor humidity, and solid fuel use in the bedroom ( β =0.19, -0.05, 1.20, 0.43, 0.02, 0.35, all P <0.05). Conclusion Solid fuel combustion significantly comtributes to PM 2.5 pollution in children s bedrooms, with more pronounced impacts observed in northern China compared to southern regions.