ObjectiveTo explore the mechanism of Huashi Baidu granules in treating influenza A （H1N1） virus infection based on the gut-lung axis. MethodsBALB/c mice were randomly assigned into a blank control group， a model control group， a positive control （oseltamivir phosphate capsules， 19.5 mg·kg^-1） group， and a Huashi Baidu granules （17.81 g·kg^-1） group. Mice in other groups except the blank control group were instilled nasally by H1N1 viral fluid for the modeling of influenza viral pneumonia and treated with corresponding drugs once daily by gavage for 5 consecutive days. The mouse lung index was calculated， and pathological changes in the lung and colon tissue were observed. Western blot was employed to quantify the expression levels of nucleotide-binding oligomeric domain-like receptor protein 3 （NLRP3）， cysteinyl aspartate-specific proteinase -1 （Caspase-1）， apoptosis-associated Speck-like protein containing a CARD （ASC）， gasdermin D （GSDMD）， interleukin-18 （IL-18）， IL-1β， and colonic tight junction protein 1 （CLDN1）， and Occludin in the lung and colon tissue. Non-targeted metabolomics was employed to analyze the metabolic profiles of the lung tissue and intestinal contents. The 16S rRNA sequencing was performed to analyze the gut microbiota structure in intestinal contents. Enzyme-linked immunosorbent assay （ELISA） was employed to measure the 5-hydroxytryptamine （5-HT） levels in the serum， lung tissue， and colon tissue. ResultsCompared with the blank control group， the model control group showed elevated lung index， marked inflammatory cell infiltration and alveolar structural destruction in the lung tissue， obvious inflammatory cell infiltration and mucosal epithelial damage in the colon tissue， upregulated protein levels of NLRP3 inflammasome pathway proteins NLRP3， Caspase-1， GSDMD， IL-1β， and IL-18 in the lung and colon tissue （P<0.05， P<0.01）， downregulated protein levels of CLDN1 and Occludin in the colon tissue （P<0.05， P<0.01）. Compared with the model control group， Huashi Baidu Granules reduced the lung index （P<0.01）， alleviated pathological damage in the lungs and colon， inhibited the expression of NLRP3， Caspase-1， GSDMD， IL-1β， and IL-18 in lung and colon tissue （P<0.05， P<0.01）， and upregulated the expression of CLDN1 and Occludin in the colon tissue （P<0.05， P<0.01）. Metabolomics analysis showed that Huashi Baidu Granules downregulated the 5-HT pathway and arachidonic acid metabolism pathway in the lung and colon tissue， while upregulating nucleotide metabolism and TCA cycle. Compared with the blank control group， the model control group exhibited elevated levels of 5-HT in the serum， lung tissue， and colon tissue （P<0.01）. The intervention with Huashi Baidu Granules lowered the levels of 5-HT in the serum （P<0.05） and the lung and colon tissue （P<0.01）. Huashi Baidu Granules increased the diversity of gut microbiota， enriched beneficial bacteria such as Blautia， and inhibited pathogenic bacteria such as Desulfovibrio. ConclusionHuashi Baidu Granules significantly alleviate lung inflammation and pathological damage in mice infected with influenza A （H1N1） virus， reshape the intestinal microecology， and repair the intestinal barrier. It may exert cross-organ regulation by inhibiting the cascade of "gutogenic 5-HT release-circulatory transport-pulmonary 5-HT receptor activation-NLRP3 inflammasome assembly." It exerts therapeutic effects on influenza viral pneumonia through the gut-lung axis. This study provides a modern biological interpretation for the TCM theories of interior-exterior relationship between the lung and large intestine and simultaneous treatment of the lung and intestine.

Lysosomes represent a promising target for cancer therapy and reducing drug resistance. However, the short treatment time and low efficiency of lysosomal targeting have limited the application in lysosome-targeting anticancer drugs. In this study, we proposed an adhesive-bandage approach and synthesized a new lysosomal targeting drug, namely long-term lysosome-targeting anticancer drug (LLAD). It contains a SLC38A9-targeting covalently bound moiety and an alkaline component both to prolong the inhibition of SLC38A9 in lysosomes and alkalinize lysosomes. Upon short term and low-dose treatment of HeLa cells, at passage 0, with LLAD, it rapidly alkalinized lysosomes and also can be detected in lysosomes even at passage 15. LLAD induced apoptosis in HeLa cells through long-term lysosomal damage, and showed better long-term anticancer effect than cisplatin in vivo. Overall, our study paves the way for developing long-term lysosomal targeting drugs to treat cancer and overcome the drug resistance of cancer cells, and also provides a candidate drug, LLAD, for treating cancer.

Objective To satisfy the normalized disinfection in the orthopedic ward,an air sterilizer based on low-temperature plasma has been developed to investigate its sterilization results in a dynamic environment of hospitalization where patients,companions and medical workers are involved.Methods This study took an orthopedics ward in the Secondary Affiliated Hospital of Xi'an Jiaotong University,as the research object,where a home-made low-temperature plasma air sterilizer was utilized.A six-stage viable Andersen cascade impactor was used to sample the natural bacteria in the ward before and after machine operation for three hours.The species and quantity of bacteria in the ward were analyzed.Results The ozone concentration in the indoor dynamic environment decreased to below 5 ppbv.After three-hour disinfection,the elimination rate of natural bacteria reached 92.35％.The final colony forming unit decreased to～150 CFU/m3;the extinction rates of Staphylococcus hominis,Bacillus cereus,molds,and Micrococcus luteus were 90.48％,80.90％,87.50％,and 92.82％respectively.Even all Haemophilus massiliensis disappeared after two-hour treatment.Conclusion Intermittent disinfection of the dynamic environment in the ward using low-temperature plasma synergistic catalyst has enabled the indoor ozone concentration to reach the first-level national standard line,effectively suppressing secondary pollution caused by ozone leakage while efficiently killing suspended microorganisms in the air,which is close to the disinfection level Ⅰenvironment specified in Hygienic Standard for Disinfection in Hospitals(GB 15982-2012).The results also show that the plasma catalytic synergistic disinfection and sterilization has the technical advantages of efficient disinfection and human-machine coexistence,which can ensure indoor air quality safety,reduce the workload of nursing staff,and thus is an effective method to assist or even replace the existing physical and chemical means.

Objective To satisfy the normalized disinfection in the orthopedic ward,an air sterilizer based on low-temperature plasma has been developed to investigate its sterilization results in a dynamic environment of hospitalization where patients,companions and medical workers are involved.Methods This study took an orthopedics ward in the Secondary Affiliated Hospital of Xi'an Jiaotong University,as the research object,where a home-made low-temperature plasma air sterilizer was utilized.A six-stage viable Andersen cascade impactor was used to sample the natural bacteria in the ward before and after machine operation for three hours.The species and quantity of bacteria in the ward were analyzed.Results The ozone concentration in the indoor dynamic environment decreased to below 5 ppbv.After three-hour disinfection,the elimination rate of natural bacteria reached 92.35％.The final colony forming unit decreased to～150 CFU/m3;the extinction rates of Staphylococcus hominis,Bacillus cereus,molds,and Micrococcus luteus were 90.48％,80.90％,87.50％,and 92.82％respectively.Even all Haemophilus massiliensis disappeared after two-hour treatment.Conclusion Intermittent disinfection of the dynamic environment in the ward using low-temperature plasma synergistic catalyst has enabled the indoor ozone concentration to reach the first-level national standard line,effectively suppressing secondary pollution caused by ozone leakage while efficiently killing suspended microorganisms in the air,which is close to the disinfection level Ⅰenvironment specified in Hygienic Standard for Disinfection in Hospitals(GB 15982-2012).The results also show that the plasma catalytic synergistic disinfection and sterilization has the technical advantages of efficient disinfection and human-machine coexistence,which can ensure indoor air quality safety,reduce the workload of nursing staff,and thus is an effective method to assist or even replace the existing physical and chemical means.

Kidney deficiency syndrome is a common clinical syndrome in traditional Chinese medicine （TCM）. With the progress of science and technology， clinical and animal experiments on kidney deficiency syndrome have made remarkable progress. Research on kidney deficiency and the nature of "kidney" involves a large number of physiological and pathological bases， which are closely related to physiological and pathological links in the human body， among which the neuroendocrine-immune network shares the closest relationship. However， there are still many challenges in modern research on kidney deficiency syndrome， such as expert consensus on clinical diagnostic criteria and evaluation indexes and optimization of animal experimental models. In the past decade， a large number of clinical and animal experiments have been reported in the literature on kidney deficiency syndrome， among which the literature focusing on the combination of disease and syndrome is predominant， and most of them focus on kidney Yang deficiency and kidney Yin deficiency， involving the exploration of many pathological mechanisms. Research on the mechanisms related to kidney deficiency syndrome encompasses multiple signaling pathways and various biochemical indicators， including the phosphatidylinositol 3-kinase/protein kinase B/nuclear factor-erythroid 2-relatedfactor-2（PI3K/Akt/Nrf2） signaling pathway， the Toll-like receptor 4/myeloid differentiation factor88/nuclear factor-κB（TLR4/MyD88/NF-κB） signaling pathway， the Janus kinase 2/signal transducer and activator of transcription 3（JAK2/STAT3） signaling pathway， Osteoprotectin/nuclear factor-κB receptor activator ligand/receptor activator of nuclear factor-κB （OPG/RANKL/RANK） signaling pathway. The biochemical indicators cover the cyclic adenosine monophosphate/cyclic guanosine monophosphate （cAMP/cGMP） ratio， Na⁺-K⁺-ATPase activity， Ca²⁺-Mg²⁺-ATPase activity， adrenocorticotropic hormone （ACTH）， polycorticosterone （CORT）， 17-OHCS， and other sex hormone indicators， providing crucial reference values for diagnosing kidney Yang deficiency or kidney Yin deficiency. The literature related to kidney deficiency syndrome over the past decade was collated and excavated， with a view to providing a reference for research on kidney deficiency syndrome.

Objective:To analyze the trajectory of residual cholesterol(RC) in a healthy check-up cohort and explore its correlation with the incidence of non-alcoholic fatty liver disease(NAFLD).Methods:A total of 2 477 participants who met the inclusion criteria in the Health Management Center of the Second Hospital of Dalian Medical University from January 2016 to December 2020 were retrospectively selected to establish a four-year RC trajectory model using the group-based trajectory model(GBTM), and the risk of NAFLD in the RC group was analyzed using Cox proportional hazards regression model. The predictive value of the Cox model was evaluated with a receiver operating characteristic(ROC) curve, and the reliability of the association between RC and NAFLD was verified through sensitivity analysis.Results:Three RC trajectory subgroups were identified low-level RC(79.21%), medium-level RC(19.86%), and high-level RC(0.93%). After 4 years of follow-up, the incidence rate of NAFLD in this cohort was 11.99%, and the incidences of NAFLD in the low-, medium-, and high-RC groups were 10.55%, 16.46%, and 39.13%, respectively. The cumulative incidence of NAFLD increased with follow-up with the highest rate observed in the high-level RC group( χ2=68.026, P<0.001). The results of Cox proportional hazards regression model indicated that the risk of NAFLD incidence in both the high-level and medium-level RC groups was greater than that in the low-level RC group. The areas under ROC curve at the 2nd, 3rd, and 4th years of follow-up were 0.777, 0.778, and 0.720, respectively, suggesting that RC has certain predictive value for new-onset NAFLD. The results were consistent after excluding 166 individuals with diabetes, hypertension, or dyslipidemia. In another sensitivity analysis, higher RC quartiles( Q2, Q3, Q4) were associated with greater NAFLD risk compared to the lowest quartile( Q1). Conclusions:The trajectory of high-level RC is a risk factor for the onset of NAFLD, and the continuous increase of high-level RC value may be an early signal of NAFLD, and timely intervention is recommended to achieve the goal of early prevention of NAFLD.

Objective:To explore the correlation between systemic immunity-inflammation index(SII) and hyperuricemia(HUA).Methods:Participants who had at least 3 health checkups in the Health Management Center of the Second Affiliated Hospital of Dalian Medical University from January 2014 to December 2022 were selected to construct a dynamic cohort. The SII, reflecting the inflammatory state of the body, was constructed using neutrophil, platelet, and lymphocyte counts. A Cox proportional hazard regression model was used to explore the association between SII and HUA in the overall population and different subgroups of the population, and sensitivity analysis was performed twice. Results:A total of 20 022 subjects were included, and the mean follow-up time was 3.67 years. After adjusting for confounding factors, each unit increase in the natural logarithm of SII(lnSII) was associated with a 24% increased risk of hyperuricemia( HR=1.24, 95% CI 1.16-1.32, P<0.001). As a categorical variable, compared with the lowest quartile array( Q1), the risk of HUA in the total population increased by 12%( HR=1.12, 95% CI 1.03-1.21, P=0.006), 14%( HR=1.14, 95% CI 1.06-1.24, P=0.001), 27%( HR=1.27, 95% CI 1.17-1.37, P<0.001) in Q2, Q3 and Q4 groups within the general population, respectively. All subgroup analysis and sensitivity analysis showed that SII was positively correlated with HUA. Conclusions:Elevated levels of SII significantly increase the risk of HUA. Assessing the body′s inflammatory status using SII can aid in risk screening and preventive management for individuals at high risk of HUA.

Objective:To analyze the trajectory of residual cholesterol(RC) in a healthy check-up cohort and explore its correlation with the incidence of non-alcoholic fatty liver disease(NAFLD).Methods:A total of 2 477 participants who met the inclusion criteria in the Health Management Center of the Second Hospital of Dalian Medical University from January 2016 to December 2020 were retrospectively selected to establish a four-year RC trajectory model using the group-based trajectory model(GBTM), and the risk of NAFLD in the RC group was analyzed using Cox proportional hazards regression model. The predictive value of the Cox model was evaluated with a receiver operating characteristic(ROC) curve, and the reliability of the association between RC and NAFLD was verified through sensitivity analysis.Results:Three RC trajectory subgroups were identified low-level RC(79.21%), medium-level RC(19.86%), and high-level RC(0.93%). After 4 years of follow-up, the incidence rate of NAFLD in this cohort was 11.99%, and the incidences of NAFLD in the low-, medium-, and high-RC groups were 10.55%, 16.46%, and 39.13%, respectively. The cumulative incidence of NAFLD increased with follow-up with the highest rate observed in the high-level RC group( χ2=68.026, P<0.001). The results of Cox proportional hazards regression model indicated that the risk of NAFLD incidence in both the high-level and medium-level RC groups was greater than that in the low-level RC group. The areas under ROC curve at the 2nd, 3rd, and 4th years of follow-up were 0.777, 0.778, and 0.720, respectively, suggesting that RC has certain predictive value for new-onset NAFLD. The results were consistent after excluding 166 individuals with diabetes, hypertension, or dyslipidemia. In another sensitivity analysis, higher RC quartiles( Q2, Q3, Q4) were associated with greater NAFLD risk compared to the lowest quartile( Q1). Conclusions:The trajectory of high-level RC is a risk factor for the onset of NAFLD, and the continuous increase of high-level RC value may be an early signal of NAFLD, and timely intervention is recommended to achieve the goal of early prevention of NAFLD.

Blood deficiency syndrome (BDS) refers to a pathological state with blood dysfunction and organ dystrophy in traditional Chinese medicine. Danggui Wuji granules (DWG) was developed from a formula containing Angelicae Sinensis Radix and Musculus et Os Galli Domestici. Herein, we investigated the mechanism of DWG in treating BDS by modulating gut microbiota. We found that DWG protected mice from BDS by elevating the levels of red blood cell count, hemoglobin, and hematocrit in peripheral blood and increasing the erythrocyte membrane Na⁺-K⁺-ATPase activity. Danggui Wuji granules changed the composition and metabolites of colonic flora. Notably, Lactobacillus, Muribaculaceae, and Alistipes were the main genera showing changes after DWG treatment. Our findings revealed that DWG presented a positive therapeutic effect on BDS in mice by regulating the gut microbiota and metabolites. The protective mechanism of DWG was associated with pathways such as metabolic pathways, biosynthesis of secondary metabolites, ABC transporters, ribosome, thyroid hormone synthesis, lysine degradation, galactose metabolism, tyrosine metabolism, etc.

In this study, we presented the isolation and characterization of eight novel seco-guaianolide sesquiterpenoids (1-8) and two known guaianolide derivatives (9 and 10), from the aerial part of Achillea alpina L.. Compounds 1-3 were identified as guaianolides bearing an oxygen insertion at the 2, 3 position, while compounds 4-8 belonged to a group of special 3-nor guaianolide sesquiterpenoids. The structural elucidation of 1-8, including their absolute configurations, were accomplished by a combination of spectroscopic data analysis and quantum electronic circular dichroism (ECD) calculations. To evaluate the potential antidiabetic activity of compounds 1-10, we investigated their effects on glucose consumption in palmitic acid (PA)-mediated HepG2-insulin resistance (IR) cells. Among the tested compounds, compound 7 demonstrated the most pronounced ability to reverse IR. Moreover, a mechanistic investigation revealed that compound 7 exerted its antidiabetic effect by reducing the production of the pro-inflammatory cytokine IL-1β, which was achieved through the suppression of the NLRP3 pathway.
Humans ; Hypoglycemic Agents/pharmacology* ; Circular Dichroism ; Cytokines ; Glucose ; Hep G2 Cells ; Insulin Resistance