Sepsis is a systemic inflammatory response syndrome caused by the invasion of pathogenic microorganisms such as bacteria. In addition to the manifestations of systemic inflammatory response syndrome and primary infection lesions， critical cases often have manifestations of organ hypoperfusion. The morbidity and mortality of sepsis have remained high in recent years， which seriously affect the quality of life of the patients. The pathogenesis of sepsis is complicated， in which uncontrollable inflammation is a key mechanism. The phosphatidylinositol 3-kinase/protein kinase B （PI3K/Akt） signaling pathway plays a key role in mediating inflammation in sepsis. The available therapies of sepsis mainly include resuscitation， anti-infection， vasoactive drugs， intensive insulin therapy， and organ support， which show limited effects of reducing the mortality. Therefore， finding new therapeutic drugs is a key problem to be solved in the clinical treatment of sepsis. In recent years， studies have shown that traditional Chinese medicine （TCM） can regulate the PI3K/Akt pathway via multiple pathways， multiple effects， and multiple targets to inhibit inflammation and curb the occurrence and development of sepsis， which has gradually become a hot spot in the prevention and treatment of sepsis. Moreover， studies have suggested that TCM has unique advantages in the treatment of sepsis. TCM can regulate the PI3K/Akt signaling pathway to inhibit inflammation， reduce oxidative stress， and control apoptosis in the prevention and treatment of sepsis. Despite the research progress， a systematic review remains to be performed regarding the TCM treatment of sepsis by regulating the PI3K/Akt signaling pathway. After reviewing relevant papers published in recent years， this study systematically summarizes the relationship between PI3K/Akt pathway and sepsis and the role of TCM in the treatment of sepsis， aiming to provide new ideas for the potential treatment of sepsis and the development of new drugs.

Objectives:To investigate the influence of the mild photothermal effect of Au nanorods on the osteogenic differentiation of MC3T3-E1 osteoblast cells.Methods:Surface modification of Au nanorods was performed with bovine serum albumin(BSA)coating.The photothermal effect,photothermal stability and characteristics of AuNRs@CTAB and AuNRs@BSA were analyzed u-sing scanning electron microscopy(SEM),transmission electron microscopy(TEM),and a near-infrared laser.The biocompatibili-ty of AuNRs@BSA was evaluated using live/dead staining and the CCK-8 assay.The influence of the mild photothermal effect of AuNRs@BSA on the osteogenic differentiation of MC3T3-E1 was assessed by ALP staining,alizarin red staining,and semi-quanti-tative analysis.Results:Biocompatible and near-infrared light-responsive AuNRs@BSA were prepared.In vitro experiments dem-onstrated that the mild photothermal effect of AuNRs@BSA increased the ALP activity and mineralization ability of MC3T3-E1(P＜0.000 1).Conclusion:The mild photothermal effect of AuNRs@BSA can promote the osteogenic differentiation of MC3T3-E1 cells.

Objective:To explore the impact of air pollution on hospital visits for mental and behavioral disorders among residents in an industrial area in Henan Province from 2016 to 2021.Methods:Daily outpatient visits data for mental and behavioral disorders were collected from Angang General Hospital in Angang Industrial Area at Anyang City between January 2016 and December 2021. And air pollutants and meteorological data during the same period were also collected. A generalized additive model was used for time-series analysis to examine the relationship between daily average concentrations of nitrogen dioxide (NO 2), sulfur dioxide (SO 2), fine particulate matter (PM 2.5), inhalable particulate matter (PM 10), carbon monoxide (CO), and ozone (O 3) with a lag of 0 to 7 days on the number of visits for mental and behavioral disorders among residents. The single-day lag effect (lag0-lag7 d) and cumulative lag effect (lag01-lag07 d) were analyzed. The smooth cubic spline function was used to fit the exposure-response relationship, and subgroup analysis was performed according to different genders, seasons and ages. Results:A total of 26 268 hospital visits for mental and behavioral disorders were collected from the industrial area between 2016 and 2021. The daily average concentrations of SO 2, NO 2, PM 2.5, PM 10, and CO were (27.50±27.33), (43.11±18.33), (73.87±60.30), (134.01±83.81) μg/m 3, and (1.72±1.03) mg/m 3, respectively. The daily maximum 8-hour average concentration of O 3 was (82.18±53.70) μg/m 3. After controlling for long-term trends, temperature, relative humidity, day of the week effects, and holiday effects, the generalized additive model analysis showed that NO 2 had a statistically significant impact on the hospital visits for mental and behavioral disorders at lag0 d, lag2 d and lag01-lag05 d and CO had a statistically significant impact at lag0-lag3 d and lag01-lag06 d (all P<0.05). NO 2 at lag02-lag04 d and CO at lag0-lag2 d and lag01-lag04 d had statistically significant effects on the visits for neurasthenia (both P<0.05). The impacts of NO 2 at lag03-lag04 d, PM 2.5 at lag3 d and lag03-lag04 d, PM 10 at lag3 d and lag03 d, and CO at lag3 d and lag01-lag05 d on visits for generalized anxiety disorder were also statistically significant (all P<0.05). After false discovery rate (FDR) correction, it was shown that for every 10 μg/m 3 increase in NO 2 and every 0.1 mg/m 3 increase in CO, the percentage increase in visits for mental and behavioral disorders and its 95% confidence interval (95% CI) were 3.38% (0.95%-5.87%) and 0.78% (0.38%-1.17%), respectively. For every 0.1 mg/m 3 increase in CO, the visits for neurasthenia increased by 0.78% (0.27%-1.29%). For every 10 μg/m 3 increase in PM 2.5 and every 0.1 mg/m 3 increase in CO, the visits for generalized anxiety disorder increased by 1.07% (0.46%-1.68%) and 1.17% (0.37%-1.97%), respectively (adjusted P<0.05). There was a linear exposure-response relationship between NO 2 and CO and the hospital visits for mental and behavioral disorders, CO and the hospital visits for neurasthenia, and CO and PM 2.5 and the hospital visits for generalized anxiety disorder ( P<0.05 for the overall association test and P>0.05 for the non-linearity test). Stratified analysis showed that air pollutants had an impact on male patients with neurasthenia, female patients with generalized anxiety disorder, individuals aged <45 years with mental and behavioral disorders, and individuals aged ≥65 years with generalized anxiety disorder. The impact of air pollutants was greater during the cold season or winter. Conclusion:Exposure to air pollution can increase hospital visits for mental and behavioral disorders among residents in industrial areas, with a higher risk among those aged<45 years old and during the cold season.

Diarrhea-predominant irritable bowel syndrome （IBS-D） is a common digestive system disease with high prevalence and recurrence rates for years， high treatment costs， and serious impacts on patients' quality of life and economic burden. Therefore， it is important to explore new and safe treatment methods. The pathogenesis of IBS-D is complex， in which the gut-brain axis is a key factor. The gut-brain axis， a bidirectional signaling pathway connecting the gastrointestinal tract and the central nervous system， regulates gastrointestinal motility， secretion， and immune responses， playing a key role in the occurrence and development of IBS-D. Up to now， antidiarrheal agents， probiotics， and neurotransmitter modulators are the main methods for the clinical treatment of IBS-D. Although they can partially curb the progression of this disease， the therapeutic effects remain to be improved. Studies have confirmed that traditional Chinese medicine （TCM） has significant advantages in the treatment of IBS-D since it can regulate the gut-brain axis via multiple pathways and targets to improve the gastrointestinal motility and strengthen immune defenses. However， there is a lack of systematic reviews on the regulation of the gut-brain axis by TCM in the treatment of IBS-D. Based on the review of IBS-D-related articles published in recent years， this paper systematically summarized the relationship between the gut-brain axis and IBS-D and the role of TCM in the treatment， providing new ideas for the treatment of IBS-D.

Objective:To explore the impact of air pollution on hospital visits for mental and behavioral disorders among residents in an industrial area in Henan Province from 2016 to 2021.Methods:Daily outpatient visits data for mental and behavioral disorders were collected from Angang General Hospital in Angang Industrial Area at Anyang City between January 2016 and December 2021. And air pollutants and meteorological data during the same period were also collected. A generalized additive model was used for time-series analysis to examine the relationship between daily average concentrations of nitrogen dioxide (NO 2), sulfur dioxide (SO 2), fine particulate matter (PM 2.5), inhalable particulate matter (PM 10), carbon monoxide (CO), and ozone (O 3) with a lag of 0 to 7 days on the number of visits for mental and behavioral disorders among residents. The single-day lag effect (lag0-lag7 d) and cumulative lag effect (lag01-lag07 d) were analyzed. The smooth cubic spline function was used to fit the exposure-response relationship, and subgroup analysis was performed according to different genders, seasons and ages. Results:A total of 26 268 hospital visits for mental and behavioral disorders were collected from the industrial area between 2016 and 2021. The daily average concentrations of SO 2, NO 2, PM 2.5, PM 10, and CO were (27.50±27.33), (43.11±18.33), (73.87±60.30), (134.01±83.81) μg/m 3, and (1.72±1.03) mg/m 3, respectively. The daily maximum 8-hour average concentration of O 3 was (82.18±53.70) μg/m 3. After controlling for long-term trends, temperature, relative humidity, day of the week effects, and holiday effects, the generalized additive model analysis showed that NO 2 had a statistically significant impact on the hospital visits for mental and behavioral disorders at lag0 d, lag2 d and lag01-lag05 d and CO had a statistically significant impact at lag0-lag3 d and lag01-lag06 d (all P<0.05). NO 2 at lag02-lag04 d and CO at lag0-lag2 d and lag01-lag04 d had statistically significant effects on the visits for neurasthenia (both P<0.05). The impacts of NO 2 at lag03-lag04 d, PM 2.5 at lag3 d and lag03-lag04 d, PM 10 at lag3 d and lag03 d, and CO at lag3 d and lag01-lag05 d on visits for generalized anxiety disorder were also statistically significant (all P<0.05). After false discovery rate (FDR) correction, it was shown that for every 10 μg/m 3 increase in NO 2 and every 0.1 mg/m 3 increase in CO, the percentage increase in visits for mental and behavioral disorders and its 95% confidence interval (95% CI) were 3.38% (0.95%-5.87%) and 0.78% (0.38%-1.17%), respectively. For every 0.1 mg/m 3 increase in CO, the visits for neurasthenia increased by 0.78% (0.27%-1.29%). For every 10 μg/m 3 increase in PM 2.5 and every 0.1 mg/m 3 increase in CO, the visits for generalized anxiety disorder increased by 1.07% (0.46%-1.68%) and 1.17% (0.37%-1.97%), respectively (adjusted P<0.05). There was a linear exposure-response relationship between NO 2 and CO and the hospital visits for mental and behavioral disorders, CO and the hospital visits for neurasthenia, and CO and PM 2.5 and the hospital visits for generalized anxiety disorder ( P<0.05 for the overall association test and P>0.05 for the non-linearity test). Stratified analysis showed that air pollutants had an impact on male patients with neurasthenia, female patients with generalized anxiety disorder, individuals aged <45 years with mental and behavioral disorders, and individuals aged ≥65 years with generalized anxiety disorder. The impact of air pollutants was greater during the cold season or winter. Conclusion:Exposure to air pollution can increase hospital visits for mental and behavioral disorders among residents in industrial areas, with a higher risk among those aged<45 years old and during the cold season.

This study aims to comprehensively analyze the material basis of toad visceral oil(hereafter referred to as toad oil), and explore the pharmacological effect of toad oil on atopic dermatitis(AD). Ultra-high performance liquid chromatography-linear ion trap/orbitrap high-resolution mass spectrometry(UHPLC-LTQ-Orbitrap-MS) and gas chromatography-mass spectrometry(GC-MS) were employed to comprehensively identify the chemical components in toad oil. The animal model of AD was prepared by the hapten stimulation method. The modeled animals were respectively administrated with positive drug(0.1% hydrocortisone butyrate cream) and low-and high-doses(1%, 10%) of toad oil by gavage. The effect of toad oil on AD was evaluated with the AD score, ear swelling rate, spleen index, and pathological section results as indicators. A total of 99 components were identified by UHPLC-LTQ-Orbitrap-MS, including 14 bufadienolides, 7 fatty acids, 6 alkaloids, 10 ketones, 18 amides, and other compounds. After methylation of toad oil samples, a total of 20 compounds were identified by GC-MS. Compared with the model group, the low-and high-dose toad oil groups showed declined AD score, ear swelling rate, and spleen index, alleviated skin lesions, and reduced infiltrating mast cells. This study comprehensively analyzes the chemical composition and clarifies the material basis of toad oil. Meanwhile, this study proves that toad oil has a good therapeutic effect on AD and is a reserve resource of traditional Chinese medicine for external use in the treatment of AD.
Animals ; Dermatitis, Atopic/immunology* ; Disease Models, Animal ; Mice ; Male ; Gas Chromatography-Mass Spectrometry ; Humans ; Bufonidae ; Oils/administration & dosage* ; Chromatography, High Pressure Liquid ; Female ; Mice, Inbred BALB C

Ulcerative colitis (UC) is a chronic inflammatory disorder with a complex etiology, characterized by intestinal inflammation and barrier dysfunction. Platycodon grandiflorus polysaccharides (PGP), the primary component of Platycodon grandiflorus, and hesperidin (Hesp), a prominent active component in Citrus aurantium L. (CAL), have both demonstrated anti-inflammatory properties. This study aims to elucidate the underlying mechanism of the synergistic effect of PGP combined with Hesp on UC, focusing on the coordinated interaction between the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) and Janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) signaling pathways. A mouse model of UC induced by dextran sulfate sodium (DSS) and a cell model using lipopolysaccharide (LPS)-induced RAW264.7/IEC6 cells were employed to investigate the in vitro and in vivo anti-inflammatory effects of PGP combined with Hesp on UC and its potential mechanism of action. The results indicated that compared to the effects of either drug alone, the combination of PGP and Hesp significantly modulated inflammatory factor levels, inhibited oxidative stress, regulated colonic mucosal immunity, suppressed apoptosis, and restored intestinal barrier function in vitro and in vivo. Further in vitro studies revealed that PGP significantly inhibited the PI3K/AKT signaling pathway, while Hesp significantly inhibited the JAK2/STAT3 signaling pathway. The use of inhibitors and activators targeting both pathways validated the synergistic effects of PGP combined with Hesp on the PI3K/AKT and JAK2/STAT3 signaling pathways. These findings suggest that PGP combined with Hesp exhibits a synergistic effect on DSS-induced colitis, potentially mediated through the phosphatase and tensin homolog (PTEN)/PI3K/AKT and interleukin-6 (IL-6)/JAK2/STAT3 signaling pathways.
Animals ; STAT3 Transcription Factor/genetics* ; Janus Kinase 2/genetics* ; Polysaccharides/administration & dosage* ; Colitis, Ulcerative/chemically induced* ; Mice ; Signal Transduction/drug effects* ; Proto-Oncogene Proteins c-akt/genetics* ; Drug Synergism ; Male ; Hesperidin/administration & dosage* ; Platycodon/chemistry* ; Phosphatidylinositol 3-Kinases/genetics* ; Disease Models, Animal ; RAW 264.7 Cells ; Mice, Inbred C57BL

Objectives:To investigate the influence of the mild photothermal effect of Au nanorods on the osteogenic differentiation of MC3T3-E1 osteoblast cells.Methods:Surface modification of Au nanorods was performed with bovine serum albumin(BSA)coating.The photothermal effect,photothermal stability and characteristics of AuNRs@CTAB and AuNRs@BSA were analyzed u-sing scanning electron microscopy(SEM),transmission electron microscopy(TEM),and a near-infrared laser.The biocompatibili-ty of AuNRs@BSA was evaluated using live/dead staining and the CCK-8 assay.The influence of the mild photothermal effect of AuNRs@BSA on the osteogenic differentiation of MC3T3-E1 was assessed by ALP staining,alizarin red staining,and semi-quanti-tative analysis.Results:Biocompatible and near-infrared light-responsive AuNRs@BSA were prepared.In vitro experiments dem-onstrated that the mild photothermal effect of AuNRs@BSA increased the ALP activity and mineralization ability of MC3T3-E1(P＜0.000 1).Conclusion:The mild photothermal effect of AuNRs@BSA can promote the osteogenic differentiation of MC3T3-E1 cells.

Sepsis is one of the common severe diseases caused by the dysregulated host response to infection， which seriously threatens the life and health of human beings all over the world. The incidence and mortality of the disease are extremely high， and it has always been an urgent problem to be solved in the field of acute and critical diseases. At present， anti-infection， fluid resuscitation， mechanical ventilation and other programs are most used in clinic to treat sepsis， but their poor prognosis and high cost and other issues remain to be resolved. Therefore， it is necessary to explore a new， efficient， safe and inexpensive drug and treatment model at this stage. The treatment of traditional Chinese medicine （TCM） is based on syndrome differentiation and holistic concept. It can effectively regulate the progression of sepsis， maintain the homeostasis of the body， and has fewer adverse reactions. It has achieved good clinical results. In recent years， a large number of studies have shown that TCM can reduce the inflammatory response by regulating the Toll-like receptor 4（TLR4） signaling pathway， thereby reducing the severity and mortality of sepsis patients. However， there is still a lack of systematic exposition of TCM regulating TLR4 signaling pathway in the treatment of sepsis. Therefore， this article summarizes the relationship between TLR4 signaling pathway and sepsis and the mechanism of TCM in the disease by searching and consulting relevant literature in recent years. It is found that some Chinese medicine monomers and active ingredients， Chinese medicine compounds and Chinese medicine preparations can effectively reduce systemic inflammatory response， repair organ damage and improve the prognosis of sepsis by inhibiting the activation of TLR4 signaling pathway. However， due to various limitations， some studies have directly focused on the differential expression and function of TLR4， ignoring the downstream molecular expression and phenotypic effects of TLR4. The alternative mechanism， relationship and specific molecular mechanism of the pathway are still unclear. There are problems such as unclear pharmacokinetics and unclear mechanism in the pro- and anti-inflammatory balance， which need to be further studied and explored in order to provide new ideas for the potential treatment and drug development for sepsis.

Sepsis is a life-threatening organ dysfunction caused by infection. Janus kinase/signal transducer and activator of transcription （JAK/STAT） signaling pathway plays a key role in the regulation of inflammatory response， oxidative stress and apoptosis. Some traditional Chinese medicine monomers， such as flavonoids （such as taxifolin）， alkaloids （such as sinomenine）， and stilbenes （such as piceatannol） can exert anti-inflammatory， anti-oxidation， and inhibition of apoptosis by regulating the JAK/ STAT signaling pathway， which is helpful to improve sepsis. Traditional Chinese medicine compounds （such as Zuojinfang） and traditional Chinese medicine injections （such as Astragalus injection， Xuebijing injection） can also inhibit inflammation， protect organ function， and reduce sepsis-related damage by regulating JAK/STAT signaling pathway. Although traditional Chinese medicine has shown great potential in the prevention and treatment of sepsis， the current research mainly focuses on in vitro and animal models， and more relative clinical researches need to be conducted.