ObjectiveTo explore the mechanism of Shenmai injection in improving cisplatin resistance in non-small cell lung cancer （NSCLC） based on the endoplasmic reticulum stress through protein kinase R-like endoplasmic reticulum kinase （PERK）/activated transcription factor 4 （ATF4）/C/EBP homologous protein （CHOP） signaling pathway. MethodsBALB/c nude mice bearing cisplatin-resistant human lung cancer cell line （A549/cisplatin） were randomly divided into four groups： Blank control group （0.9% sodium chloride）， cisplatin group （5 µg·g^-1cisplatin）， Shenmai injection group （5.2 mg·g^-1 Shenmai injection）， and combination therapy group （5.2 mg·g^-1 Shenmai injection +5 µg·g^-1cisplatin）. The drug intervention lasted for 4 weeks， and the changes in body weight and tumor volume were monitored. Hematoxylin-eosin （HE） staining was performed to observe tumor tissue pathology. Transmission electron microscopy （TEM） was used to assess the morphology of the endoplasmic reticulum. Immunohistochemical assay was conducted to measure the positive expressions of PERK， ATF4， and CHOP in tumor tissues. Western blot quantified the protein expression of immunoglobulin heavy chain binding protein （BIP）， PERK， phosphorylated PERK （p-PERK）， eukaryotic translation initiation factor 2α （eIF2α）， phosphorylated eIF2α （p-eIF2α）， ATF4， CHOP， B-cell lymphoma -2 （Bcl-2）， and Bcl-2 Associated X protein （Bax）. A549/cis cells were divided into blank group： Blank control group （normal culture medium）， cisplatin group （23.3 µmol·L^-1 cisplatin）， Shenmai Injection group （20 g·L^-1 Shenmai injection）， and combination therapy group （20 g·L^-1 Shenmai injection+23.3 µmol·L^-1 cisplatin）. Cell counting kit-8 （CCK-8） method was used to detect cell viability， TEM was used to observe the morphology of endoplasmic reticulum， and Western blot was used to detect endoplasmic reticulum stress and apoptosis-related proteins. ResultsCompared with the cisplatin group， the combination therapy group showed increased body weight （P<0.05）， decreased tumor volume （P<0.05）， and expanded endoplasmic reticulum in tumor cells. The positive expressions of PERK， ATF4， and CHOP increased （P<0.05）. Western blot revealed elevated protein expression levels of BIP， p-PERK/PERK， p-eIF2α/eIF2α， ATF4， CHOP， and Bax （P<0.05）， while Bcl-2 expression decreased （P<0.05）. As shown in the in vitro experiment， compared with the cisplatin group， the combination therapy group exhibited a reduced cell survival rate （P<0.05）. TEM revealed increased endoplasmic reticulum dilation and vesicular degeneration. Western blotting showed increased protein levels of BIP， p-PERK/PERK， p-eIF2α/eIF2α， ATF4， CHOP and Bax （P<0.05）， with decreased Bcl-2 expression （P<0.05）. ConclusionShenmai injection combined with cisplatin has a synergistic antitumor effect in NSCLC， which may be attributed to the activation of endoplasmic reticulum stress response mediated by the PERK/eIF2α/ATF4/CHOP signaling pathway and the induction of tumor cell apoptosis.

ObjectiveTaking Aurantii Fructus Immaturus juice（AFI）-processed Atractylodis Macrocephalae Rhizoma（AMR） as an example， this study aims to systematically compare the volatile and non-volatile components of AMR and its processed products， investigate the key differential components， evaluate their anti-inflammatory activities， and elucidate the synergistic mechanism of processing. MethodsThe chemical compositions of volatile and non-volatile components in AMR and AFI-processed AMR were systematically characterized using gas chromatography-mass spectrometry（GC-MS） and ultra-performance liquid chromatography-quadrupole-time-of-flight mass spectrometry（UPLC-Q-TOF-MS）， with relative mass fractions and response values determined separately. Volatile components were identified through searches in the National Institute of Standards and Technology（NIST）17 database， comparison with retention index（RI） and fragmentation pattern matching. Non-volatile components were identified by searching Waters Traditional Chinese Medicine （TCM） spectral library， in conjunction with PubChem and MassBank， characteristic fragmentation patterns and response values were also used to support identification. Differential components were screened using principal component analysis（PCA）， orthogonal partial least squares-discriminant analysis（OPLS-DA）， with variable importance in the projection（VIP） value >1. Components with high log₂fold change（FC） among major differential groups were selected as those exhibiting significant changes before and after processing. The anti-inflammatory activity of the differential compounds was evaluated by assessing their effects on nitric oxide（NO） production in a lipopolysaccharide（LPS）-induced RAW264.7 macrophage model. Enzyme-linked immunosorbent assay（ELISA） was used to detect the effects of the differential components on tumor necrosis factor（TNF）-α， interleukin（IL）-1β， IL-6， and monocyte chemotactic protein（MCP）-1 levels， and immunofluorescence（IF） was employed to assess their effects on nuclear transcription factor（NF）-κB p65 translocation， thereby elucidating the underlying molecular mechanisms. ResultsA total of 36 compounds were identified in the volatile components of AMR and AFI-processed AMR， among which， sesquiterpenes and monoterpenes were significantly increased after processing. In the non-volatile components， 36 compounds were identified， and the main differential components were flavonoids， sesquiterpenoids， and triterpenoids. Flavonoids were the primary differential components distinguishing AMR from its processed products， representing compounds directly introduced during processing. Five compounds， including atractylenolide Ⅲ， tangeritin， nobiletin， hesperidin and narirutin， were selected as representatives of three classes based on their most prominent differential expression among different compound types for subsequent anti-inflammatory activity studies. The results showed that 100 μmol·L^-1 tangerine and narirutin could significantly inhibit LPS-induced NO production（P<0.01） in a concentration-dependent manner. Tangeritin was able to significantly inhibit the levels of TNF-α and MCP-1 secreted by RAW264.7（P<0.05）， while narirutin significantly inhibited the levels of TNF-α， IL-1β， MCP-1 and IL-6（P<0.01）. IF revealed that both tangeritin and narirutin significantly blocked the translocation of NF-κB p65 from the cytoplasm to the nucleus. ConclusionAFI-processed AMR significantly alters the chemical composition profile of AMR， and the newly introduced flavonoid components during processing may be key to its enhanced anti-inflammatory effects.

OBJECTIVE To prepare an intelligent responsive liposome-hydrogel nanopreparation co-loaded with gambogic acid （GA）， and characterize its antitumor activity in vitro . METHODS GA-ICG-Lip-gel was prepared by ethanol injection and cold dissolution， incorporating GA and the photosensitizer indocyanine green （ICG）. The appearance and microscopic morphology of GA-ICG-Lip-gel were observed， its encapsulation efficiency and drug loading capacity were measured， and its photothermal conversion performance， photothermal stability， and infrared imaging properties were investigated， along with the determination of its in vitro release profile. Human breast cancer MCF-7 cells were used as objects to investigate the effects of GA-ICG-Lip-gel （or with near-infrared light irradiation） on cell viability， migration ability， and the cellular uptake capacity of GA-ICG-Lip-gel. RESULTS GA-ICG-Lip-gel existed in a solution state at room temperature and transformed into a gel state at 37 ℃. Its microstructure was dense with small pores， and its encapsulation efficiency and drug loading were （96.07±0.86） % and （6.28±1.16） %， respectively. After exposure to near-infrared light， the temperature of GA-ICG-Lip-gel rose above 42 ℃， with no significant attenuation observed in the heating curve. The heating efficiency was dependent on both the irradiation time and drug concentration. Compared to media without gelatinase， the cumulative release rate of GA-ICG-Lip-gel increased in media containing gelatinase. In vitro studies showed that GA-ICG-Lip-gel could be efficiently taken up by MCF-7 cells； GA-ICG-Lip-gel significantly inhibited the viability and migration ability of MCF-7 cells （ P ＜0.05）， and this inhibitory effect was further enhanced under near-infrared light irradiation. CONCLUSIONS This study successfully prepares GA-ICG-Lip-gel， which exhibits favorable photothermal conversion properties and temperature/enzyme dual-responsive drug release characteristics， and demonstrates significant inhibitory effects on the proliferation and migration of breast cancer cells.

Diabetic kidney disease （DKD） is one of the common microvascular complications of diabetes mellitus （DM） and a primary cause of chronic kidney disease （CKD） and end-stage renal disease （ESRD）. Inflammation is currently a hot topic in exploring the pathogenesis of DKD. Macrophages， T cells， interleukins， tumor necrosis factor， NOD-like receptor protein 3 （NLRP3） inflammasome， Janus kinase/signal transducer and activator of transcription （JAK/STAT） signaling pathway， and nuclear factor-kappa B （NF-κB）-related signaling pathway all play a role in regulating the inflammation of DKD and accelerating its progression. Astragali Radix， a Chinese herbal medicine， is widely used in the treatment of DKD and possesses strong anti-inflammatory effects. Studies have revealed that active ingredients of Astragali Radix， including polysaccharides， astragaloside Ⅳ， total flavonoids， calycosin， and quercetin， can regulate multiple signaling pathways to ameliorate the microinflammatory state and alleviate kidney damage， thereby slowing down the progression of DKD. This article systematically reviews the factors influencing the inflammation in DKD and analyzes recent research findings and mechanisms concerning active ingredients of Astragali Radix in the management of DKD inflammation， aiming to offer novel insights and directions for the prevention， treatment， and research of DKD.

Objective To study the seasonal distribution characteristics of polycyclic aromatic hydrocarbons (PAHs) in PM_2.5 in Lianyungang City, and analyze the sources of PAHs pollution, and to evaluate the health risks of PAHs in different seasons. Methods PM2.5 samples were collected regularly from January 2019 to December 2023, and 16 types of PAHs were determined by HPLC. Kruskal-Wallis H test was used to compare the concentrations of PM2.5 and PAHs in different years and seasons. The source of PAHs was analyzed by characteristic ratio and principal component analysis (PCA). Health risks were assessed using the BaP equivalent method and the incremental lifetime cancer risk (ILCR) model. Results The annual exceedance rates of PM_2.5 and BaP in Lianyungang showed a decreasing trend from 2019 to 2023. PM_2.5, total PAHs and PAHs monomers (except Ace, Flu and Acy) all showed significant seasonal differences, with the highest concentration in winter (P<0.001). The average proportion of 4-ring PAHs was the highest and the average proportion of 2-ring PAHs was the lowest. The proportion of 5-6 ring PAHs was relatively high in winter and spring. PM2.5and PAHs were negatively correlated with temperature, relative humidity and precipitation, and were positively correlated with atmospheric pressure. PM_2.5 was negatively correlated with wind speed, while some PAHs monomers were positively correlated with wind speed. The characteristic ratio and PCA results showed that the main sources of PAHs in Lianyungang City were mixed sources of road dust and vehicle emissions, oil pollution sources and biomass combustion sources. The results of ILCR showed that the highest risk was found in adults, with males slightly higher than females. In Lianyungang, the maximum value of ILCR in winter was more than 10-6 in people over 9 years old. Conclusion The main sources of PAHs in PM_2.5 in Lianyungang City are mixed sources of road dust and vehicle emissions, oil pollution sources, and biomass combustion sources. Under the current exposure level of PAHs in PM_2.5, residents have a certain potential carcinogenic risk.

OBJECTIVE To evaluate the quality of Mongolian medicine Sendeng-4 based on qualitative and quantitative analysis combined with chemical pattern recognition， in order to provide the reference for its quality control. METHODS The chemical components in Sendeng-4 were analyzed qualitatively by HPLC-Q-Exactive-MS. The contents of 16 components （methyl gallate， ethyl gallate， epicatechin， dihydromyricetin， genipin-1-O-β-D-gentiobioside， caffeic acid， catechin， corilagin， deacetylasperulosidic acid methyl ester， rutin， geniposide， luteolin， myricetin， quercetin， ferulic acid， and toosendanin） in 15 batches of Sendeng-4 （sample S1-S15） were quantitatively analyzed by HPLC-MS/MS. Cluster analysis （CA）， principal component analysis （PCA）， and orthogonal partial least squares discriminant analysis were conducted and variable importance projection （VIP） value greater than 1 was used as the index to screen the differential components. RESULTS A total of 73 chemical components were identified in Sendeng-4， including 20 flavonoids， 16 tannins， 14 organic acids， etc. According to the quantitative analysis， the results exhibited that the average contentsthe of above 16 components in 15 batches of Sendeng-4 were 3.683-7.730， 2.391-6.952， 2 275.538-4 377.491， 2 699.188-3 537.924， 858.266-1 377.393， 3.366-11.003， 140.624-315.683，414.629-978.334， 285.501-1 510.457， 27.799-48.325， 3 625.415-6 309.563， 0.506-0.656， 442.337-649.283， 47.093-59.736， 12.942-15.822， 127.738-326.649 μg/g， respectively. According to the results of CA and PCA， 15 batches of samples could be clustered into two categories: S1-S3， S5-S6， S9-S10 and S13 were clustered into one category； S4， S7-S8， S11-S12， S14-S15 were clustered into one category. VIP values of geniposide， epicatechin， deacetylasperulosidic acid methyl ester and genipin-1-O- β-D-gentiobioside were all greater than 1. CONCLUSIONS HPLC-Q-Exactive-MS and HPLC-MS/MS techniques are employed for the qualitative and quantitative analysis of Sendeng-4. Through chemical pattern recognition analysis， four differential components are identified: geniposide， epicatechin， deacetylasperulosidic acid methyl ester， and genipin-1-O-β-D-gentiobioside.

Retinal displacement refers to the strong fluorescent lines parallel to the retinal vessels that are detected through autofluorescence examination after rhegmatogenous retinal detachment(RRD)surgery. Actually, even if patients with RRD achieve macroscopic structural reattachment after the operation, the visual function of some patients remains suboptimal. This is associated with the incomplete recovery of retinal function, and retinal displacement is one of the critical influencing factors. This paper reviews the related concepts of retinal displacement and systematically summarizes the incidence of retinal displacement after RRD surgery and its impact on function, the possible mechanisms of retinal displacement, and the influence of various factors on the occurrence of retinal displacement reported in the recent 5 a. It is conducive to enabling surgeons to conduct better design and planning for retinal reattachment surgeries, then achieve higher integrity of retinal function recovery, and enable patients to obtain better postoperative visual function.

ObjectiveTo investigate the ameliorative effect of paeonol on acute alcohol-induced hepatic inflammation in mice via the regulation of the short-chain fatty acids （SCFAs）-specific receptor GPR43/mitogen-activated protein kinase （MAPK） signaling pathway. MethodsC57BL/6 mice were randomly divided into five groups： blank control group， model group， low-dose paeonol group （120 mg·kg^-1）， high-dose paeonol group （480 mg·kg^-1）， and silybin group （36.8 mg·kg^-1）. A mouse model of alcohol-induced liver disease （ALD） was established by ad libitum administration of a Lieber-DeCarli alcohol liquid diet. Serum lipid levels， liver function， inflammatory cytokines， and oxidative stress markers were measured. Liver hematoxylin-eosin （HE） staining and Oil Red O staining were performed to validate successful modeling. Western blot analysis was used to assess the expression levels of zonula occludens-1 （ZO-1）， Claudin-1， and proteins related to the GPR43/MAPK signaling pathway in the colonic tissue. Immunohistochemistry was employed to detect the protein expression of GPR43， ZO-1， and Claudin-1 in the colon. Then 16S rDNA sequencing was performed to analyze differences in intestinal flora between the model group and the high-dose paeonol group. Additionally， fecal microbiota transplantation （FMT） experiments were conducted to validate the regulatory effect of paeonol on ALD via modulation of intestinal flora. ResultsCompared with the blank control group， the model group showed significantly elevated serum lipid levels， oxidative stress， and inflammatory cytokine expression （P<0.01）. Liver histology revealed increased inflammatory infiltration and lipid droplet accumulation. Colonic mucosal injury and impaired intestinal barrier function were observed. Levels of MAPK pathway-related proteins in the colonic tissue were upregulated （P<0.01）， while GPR43， ZO-1， and Claudin-1 protein expression levels were significantly decreased （P<0.01）. The composition and abundance of the intestinal flora were markedly altered， with a reduced Bacteroidetes-to-Firmicutes ratio and decreased relative abundances of Eubacterium， Parabacteroides， Erysipelothrix， and Adlercreutzia， alongside increased abundances of Clostridium butyricum， Enterococcus， and Helicobacter pylori in the model group. Compared with the model group， paeonol significantly reduced serum lipid levels， oxidative stress responses， and the expression of inflammatory cytokines in ALD mice （P<0.05， P<0.01）. It also attenuated hepatic lipid accumulation， restored intestinal barrier function， and repaired the structural integrity of liver and colonic tissues. The protein expression levels of ZO-1， Claudin-1， and GPR43 in the colonic tissue were significantly increased （P<0.05， P<0.01）， while those of MAPK pathway-related proteins were significantly decreased （P<0.05， P<0.01）. The intestinal flora dysbiosis was effectively alleviated， rendering its composition closer to that of normal mice. The efficacy of paeonol in modulating ALD was further confirmed by FMT experiments， supporting its mechanistic involvement in the SCFAs-GPR43/MAPK signaling pathway. ConclusionPaeonol exerts a protective effect against ALD in mice， which may be mediated through regulation of the SCFAs-GPR43/MAPK signaling pathway， thereby achieving anti-inflammatory effects and improving intestinal barrier function.

ObjectiveTo investigate the ameliorative effect of paeonol on acute alcohol-induced hepatic inflammation in mice via the regulation of the short-chain fatty acids （SCFAs）-specific receptor GPR43/mitogen-activated protein kinase （MAPK） signaling pathway. MethodsC57BL/6 mice were randomly divided into five groups： blank control group， model group， low-dose paeonol group （120 mg·kg^-1）， high-dose paeonol group （480 mg·kg^-1）， and silybin group （36.8 mg·kg^-1）. A mouse model of alcohol-induced liver disease （ALD） was established by ad libitum administration of a Lieber-DeCarli alcohol liquid diet. Serum lipid levels， liver function， inflammatory cytokines， and oxidative stress markers were measured. Liver hematoxylin-eosin （HE） staining and Oil Red O staining were performed to validate successful modeling. Western blot analysis was used to assess the expression levels of zonula occludens-1 （ZO-1）， Claudin-1， and proteins related to the GPR43/MAPK signaling pathway in the colonic tissue. Immunohistochemistry was employed to detect the protein expression of GPR43， ZO-1， and Claudin-1 in the colon. Then 16S rDNA sequencing was performed to analyze differences in intestinal flora between the model group and the high-dose paeonol group. Additionally， fecal microbiota transplantation （FMT） experiments were conducted to validate the regulatory effect of paeonol on ALD via modulation of intestinal flora. ResultsCompared with the blank control group， the model group showed significantly elevated serum lipid levels， oxidative stress， and inflammatory cytokine expression （P<0.01）. Liver histology revealed increased inflammatory infiltration and lipid droplet accumulation. Colonic mucosal injury and impaired intestinal barrier function were observed. Levels of MAPK pathway-related proteins in the colonic tissue were upregulated （P<0.01）， while GPR43， ZO-1， and Claudin-1 protein expression levels were significantly decreased （P<0.01）. The composition and abundance of the intestinal flora were markedly altered， with a reduced Bacteroidetes-to-Firmicutes ratio and decreased relative abundances of Eubacterium， Parabacteroides， Erysipelothrix， and Adlercreutzia， alongside increased abundances of Clostridium butyricum， Enterococcus， and Helicobacter pylori in the model group. Compared with the model group， paeonol significantly reduced serum lipid levels， oxidative stress responses， and the expression of inflammatory cytokines in ALD mice （P<0.05， P<0.01）. It also attenuated hepatic lipid accumulation， restored intestinal barrier function， and repaired the structural integrity of liver and colonic tissues. The protein expression levels of ZO-1， Claudin-1， and GPR43 in the colonic tissue were significantly increased （P<0.05， P<0.01）， while those of MAPK pathway-related proteins were significantly decreased （P<0.05， P<0.01）. The intestinal flora dysbiosis was effectively alleviated， rendering its composition closer to that of normal mice. The efficacy of paeonol in modulating ALD was further confirmed by FMT experiments， supporting its mechanistic involvement in the SCFAs-GPR43/MAPK signaling pathway. ConclusionPaeonol exerts a protective effect against ALD in mice， which may be mediated through regulation of the SCFAs-GPR43/MAPK signaling pathway， thereby achieving anti-inflammatory effects and improving intestinal barrier function.

Objective To investigate the expression of Cyclin F in clear cell renal cell carcinoma (ccRCC), its clinicopathological characteristics, and its effect on the biological behavior of renal cancer cell lines Methods RT-qPCR and Western blot were used to detect the mRNA and protein expression of Cyclin F in fresh ccRCC specimens. Immunohistochemistry assay was performed to detect the expression of Cyclin F protein in 80 paraffin samples. CCK-8 assay, scratch assay, and flow cytometry were conducted to determine the effects of Cyclin F overexpression on the proliferation, migration, and apoptosis of renal cancer cell lines. Results The expression of Cyclin F in cancer tissues was higher than that in adjacent tissues at the mRNA level (P<0.0285). The expression of Cyclin Fprotein in cancer tissues was lower than that in adjacent tissues (P<0.001). The analysis of clinicopathological parameters showed that the low expression of Cyclin F was correlated with WHO/ISUP grade, Ki67 index, and age (P=0.041, 0.047, 0.008,). In vitro experiments confirmed that overexpression of Cyclin F promoted the proliferation (P<0.001) and migratory ability (24 h P=0.003, 48 h P=0.0058) of the RCC 786-O cell line, while inhibiting apoptosis (P=0.0019). Conclusion The low expression of Cyclin F protein in ccRCC tissuesis associated with high ISUP grade, high Ki67 index, oldage, and prognosis of patients.