OBJECTIVE: To explore the potential effects and mechanisms of Liang-Ge-San (LGS) for the treatment of acute respiratory distress syndrome (ARDS) through network pharmacology analysis and to verify LGS activity through biological experiments. METHODS: The key ingredients of LGS and related targets were obtained from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform. ARDS-related targets were selected from GeneCards and DisGeNET databases. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses were performed using the Metascape Database. Molecular docking analysis was used to confirm the binding affinity of the core compounds with key therapeutic targets. Finally, the effects of LGS on key signaling pathways and biological processes were determined by in vitro and in vivo experiments. RESULTS: A total of LGS-related targets and 496 ARDS-related targets were obtained from the databases. Network pharmacological analysis suggested that LGS could treat ARDS based on the following information: LGS ingredients luteolin, wogonin, and baicalein may be potential candidate agents. Mitogen-activated protein kinase 14 (MAPK14), recombinant V-Rel reticuloendotheliosis viral oncogene homolog A (RELA), and tumor necrosis factor alpha (TNF-α) may be potential therapeutic targets. Reactive oxygen species metabolic process and the apoptotic signaling pathway were the main biological processes. The p38MAPK/NF-κ B signaling pathway might be the key signaling pathway activated by LGS against ARDS. Moreover, molecular docking demonstrated that luteolin, wogonin, and baicalein had a good binding affinity with MAPK14, RELA, and TNF α. In vitro experiments, LGS inhibited the expression and entry of p38 and p65 into the nucleation in human bronchial epithelial cells (HBE) cells induced by LPS, inhibited the inflammatory response and oxidative stress response, and inhibited HBE cell apoptosis (P<0.05 or P<0.01). In vivo experiments, LGS improved lung injury caused by ligation and puncture, reduced inflammatory responses, and inhibited the activation of p38MAPK and p65 (P<0.05 or P<0.01). CONCLUSION LGS could reduce reactive oxygen species and inflammatory cytokine production by inhibiting p38MAPK/NF-κ B signaling pathway, thus reducing apoptosis and attenuating ARDS.
Drugs, Chinese Herbal/pharmacology* ; Respiratory Distress Syndrome/enzymology* ; p38 Mitogen-Activated Protein Kinases/metabolism* ; NF-kappa B/metabolism* ; Animals ; Signal Transduction/drug effects* ; Molecular Docking Simulation ; Humans ; Male ; Network Pharmacology ; Apoptosis/drug effects* ; Mice

Elderly patients are a crucial population for medical treatment and referral.The establishment of standardized and efficient referral channels is essential for enhancing the referral process, improving treatment outcomes for the elderly, and optimizing the allocation of medical resources.Referral network analysis examines the integrity, structure, and dynamics of referrals to infer the characteristics of the network.This can offer insights for enhancing referral policies and elevating medical service standards.While existing research predominantly concentrates on referral networks within the general population, there is a noticeable gap in studies focusing on elderly patients.This review article assesses domestic and international research on networks formed between medical institutions or physicians through patient referrals, aiming to inform and enhance referral policies in our country.

To clarify the occurrence and distribution of broad bean wilt virus 2(BBWV2) on Rehmannia glutinosa, this study collected 87 R. glutinosa samples with typical symptoms of viral disease such as chlorosis and crumple from Wenxian county and Wuzhi county in Jiaozuo city, Henan province and Qiaocheng district in Bozhou city, Anhui province. The BBWV2 CP target band was amplified from 37 R. glutinosa samples by RT-PCR technology. The total detection rate reached 42.5%, among which 43.0% was detected in samples from Henan province. The detection rate in samples from Anhui province was 37.5%. 37 BBWV2 CP sequences were obtained by cloning and sequencing of BBWV2 positive samples(data has been submitted to GenBank, accession numbers: PP407959-PP407995), and the sequence analysis of these CP sequences with 91 other BBWV2 isolates in GenBank showed a high genetic diversity with a consistency rate of 70.8%-100%. Meanwhile, phylogenetic analysis showed that BBWV2 could be divided into three groups according to CP sequences, among which the BBWV2 in R. glutinosa isolates obtained in this study were all located in group 3. This study identified the differences in the occurrence, distribution, and genetic diversity of BBWV2 in R. glutinosa from Henan province and Anhui province and provided a theoretical basis for the prevention and control of BBWV2.
Rehmannia/virology* ; Phylogeny ; Plant Diseases/virology* ; China ; Molecular Sequence Data ; Fabavirus/classification*

This study aims to explore the effects and action mechanisms of the active ingredients in Buyang Huanwu Decoction(BYHWD), namely tetramethylpyrazine(TMP) and hydroxy-safflor yellow A(HSYA), on oxygen-glucose deprivation/reglucose-reoxygenation(OGD/R)-induced inflammation and oxidative stress of microglia(MG). Network pharmacology was used to screen the effective monomer ingredients of BYHWD and determine the safe concentration range for each component. Inflammation and oxidative stress models were established to further screen the best ingredient combination and optimal concentration ratio with the most effective anti-inflammatory and antioxidant effects. OGD/R BV2 cell models were constructed, and BV2 cells in the logarithmic growth phase were divided into a normal group, a model group, an HSYA group, a TMP group, and an HSYA + TMP group. Enzyme-linked immunosorbent assay(ELISA) was used to detect the levels of inflammatory cytokines such as interleukin-1β(IL-1β), tumor necrosis factor-α(TNF-α), and interleukin-6(IL-6). Oxidative stress markers, including superoxide dismutase(SOD), nitric oxide(NO), and malondialdehyde(MDA), were also measured. Western blot was used to analyze the protein expression of both inflammation-related pathway [Toll-like receptor 4(TLR4)/nuclear factor-kappa B(NF-κB)] and oxidative stress-related pathway [nuclear factor erythroid 2-related factor 2(Nrf2)/heme oxygenase-1(HO-1)]. Immunofluorescence was used to assess the expression of proteins such as inducible nitric oxide synthase(iNOS) and arginase-1(Arg-1). The most effective ingredients for anti-inflammatory and antioxidant effects in BYHWD were TMP and HSYA. Compared to the normal group, the model group showed significantly increased levels of IL-1β, TNF-α, IL-6, NO, and MDA, along with significantly higher protein expression of NF-κB, TLR4, Nrf2, and HO-1 and significantly lower SOD levels. The differences between the two groups were statistically significant. Compared to the model group, both the HSYA group and the TMP group showed significantly reduced levels of IL-1β, TNF-α, IL-6, NO, and MDA, lower expression of NF-κB and TLR4 proteins, higher levels of SOD, and significantly increased protein expression of Nrf2 and HO-1. Additionally, the expression of the M1-type MG marker iNOS was significantly reduced, while the expression of the M2-type MG marker Arg-1 was significantly increased. The results of the HSYA group and the TMP group had statistically significant differences from those of the model group. Compared to the HSYA group and the TMP group, the HSYA + TMP group showed further significant reductions in IL-1β, TNF-α, IL-6, NO, and MDA levels, along with significant reductions in NF-κB and TLR4 protein expression, an increase in SOD levels, and elevated Nrf2 and HO-1 protein expression. Additionally, the expression of the M1-type MG marker iNOS was reduced, while the M2-type MG marker Arg-1 expression increased significantly in the HSYA + TMP group compared to the TMP or HSYA group. The differences in the results were statistically significant between the HSYA + TMP group and the TMP or HSYA group. The findings indicated that the combined use of HSYA and TMP, the active ingredients of BYHWD, can effectively inhibit OGD/R-induced inflammation and oxidative stress of MG, showing superior effects compared to the individual use of either component.
Oxidative Stress/drug effects* ; Drugs, Chinese Herbal/pharmacology* ; Animals ; Mice ; Glucose/metabolism* ; Cell Line ; Inflammation/genetics* ; Oxygen/metabolism* ; Pyrazines/pharmacology* ; Microglia/metabolism* ; NF-E2-Related Factor 2/immunology* ; NF-kappa B/immunology* ; Toll-Like Receptor 4/immunology* ; Anti-Inflammatory Agents/pharmacology* ; Humans

OBJECTIVES: To investigate the association between insulin resistance and uterine volume in girls with idiopathic central precocious puberty (ICPP). METHODS: A retrospective study was conducted involving 61 girls diagnosed with ICPP who visited the pediatric growth and development clinic of the Third Affiliated Hospital of Zhengzhou University between January 2022 and September 2024, designated as the ICPP group, and 61 normally developing girls as the control group. The differences in insulin resistance index (homeostasis model assessment of insulin resistance, HOMA-IR), uterine volume, and other indicators between the two groups were compared, and the relationship between insulin resistance and uterine volume in these girls was analyzed. RESULTS: The uterine volume and HOMA-IR level in the ICPP group were significantly higher than those in the control group (P<0.05). Correlation analysis revealed that there was a positive correlation between HOMA-IR level and uterine volume in the ICPP group (r_s=0.643, P<0.001). Multiple linear regression analysis indicated that as HOMA-IR increased,uterine volume in the girls tended to increase (P<0.05). CONCLUSIONS There is an association between insulin resistance and uterine volume in girls with ICPP, and as HOMA-IR increases, uterine volume in the girls also increases.
Humans ; Female ; Insulin Resistance ; Puberty, Precocious/metabolism* ; Uterus/pathology* ; Child ; Retrospective Studies ; Organ Size ; Linear Models

OBJECTIVE: To investigate the relationship between angiotensin Ⅱ type 1 receptor autoantibody (AT1-AA) and semen parameters. Methods： The semen samples of 820 male patients who were treated in the Reproductive Medicine Center of Taiyuan Central Hospital from August 2022 to August 2023 were retrospectively analyzed. The levels of AT1-AA and Ang Ⅱ of semen were detected by ELISA, and the function of AT1-AA was detected by cardiomyocyte beating assay in suckling rats. The patients were divided into low group, median group and high group according to the OD values of AT1-AA. The differences in general data and semen parameters between different groups were analyzed. And the correlation between AT1-AA level and semen parameters in semen of all study subjects was analyzed by the method of Spearman analysis. And the relationships between AT1-AA OD value, Ang Ⅱ level and semen parameters in the AT1-AA high value group were analyzed as well. RESULTS: AT1-AA was present in semen with good function. There was no significant difference in the general data of patients in different AT1-AA levels (P>0.05). In the comparison of semen parameters among the groups with different levels of AT1-AA, there were differences in sperm concentration, PR concentration, NP％, and ALH among the three groups (P<0.05). And AT1-AA OD value was positively correlated with total sperm count, sperm concentration, PR concentration, and NP％, and negatively correlated with semen volume (P<0.05). In the AT1-AA high value group, the OD value of AT1-AA in semen was negatively correlated with inactive sperm, and positively correlated with total motility (［PR+NP］％), curve rate, mean path rate, and ALH. However, there was no correlation between the level of Ang Ⅱ in semen and semen parameters (P>0.05). CONCLUSION The presence of AT1-AA in semen may be associated with the promotion of sperm motility.
Male ; Humans ; Autoantibodies ; Sperm Motility ; Semen ; Retrospective Studies ; Receptor, Angiotensin, Type 1/immunology* ; Animals ; Rats ; Angiotensin II ; Adult ; Sperm Count ; Semen Analysis ; Receptor, Angiotensin, Type 2/immunology*

In recent years,significant breakthroughs have been achieved in the immunotherapy for Alzheimer's disease.In line with global advancements,two anti-amyloid-β monoclonal antibodies have been approved and successfully launched in China for clinical use.Lecanemab and Donanemab were officially used in June 2024 and April 2025 in China,respectively.In order to standardize the rational and safe application of anti-amyloid-β monoclonal antibodies for Alzheimer's disease in China,this article integrates recom-mendations from the clinical trials and real-world experience from the author's team and domestic peers to further update the recom-mendations for the clinical use of anti-amyloid-β monoclonal antibody based on the 2024 version.It includes indications for therapy,pre-treatment evaluation and preparation,administration protocols and safety measures during treatment,and post-treatment monitor-ing strategies.

The aryl hydrocarbon receptor (AhR) plays a crucial role in regulating many physiological processes. Activating the AhR-CYP1A1 axis has emerged as a novel therapeutic strategy against various inflammatory diseases. Here, a practical in situ cell-based fluorometric assay was constructed to screen AhR-CYP1A1 axis modulators, via functional sensing of CYP1A1 activities in live cells. Firstly, a cell-permeable, isoform-specific enzyme-activable fluorogenic substrate for CYP1A1 was rationally constructed for in-situ visualizing the dynamic changes of CYP1A1 function in living systems, which was subsequently used for discovering the efficacious modulators of the AhR-CYP1A1 axis. Following screening of a compound library, LAC-7 was identified as an efficacious activator of the AhR-CYP1A1 axis, which dose-dependently up-regulated the expression levels of both CYP1A1 and AhR in multiple cell lines. LAC-7 also suppressed macrophage M1 polarization and reduced the levels of inflammatory factors in LPS-induced bone marrow-derived macrophages. Animal tests showed that LAC-7 could significantly mitigate DSS-induced ulcerative colitis and LPS-induced acute lung injury in mice, and markedly reduced the levels of multiple inflammatory factors. Collectively, an optimized fluorometric cell-based assay was devised for in situ functional imaging of CYP1A1 activities in living systems, which strongly facilitated the discovery of efficacious modulators of the AhR-CYP1A1 axis as novel anti-inflammatory agents.

OBJECTIVE: The present study evaluated the effects of deep acupuncture at Weizhong acupoint (BL40) on bladder function and brain activity in a rat model of overactive bladder (OAB), and investigated the possible mechanisms around the acupuncture area that initiate the effects of acupuncture. METHODS: Adult female Sprague-Dawley rats were randomly divided into six groups, comprising a control group, model group, group treated with deep acupuncture at BL40, group treated with shallow acupuncture at BL40, group treated with acupuncture at non-acupoint next to BL40, and group treated with acupuncture at Xuanzhong (GB39). Urodynamic evaluation was used to observe the urination, and functional magnetic resonance imaging was used to observe the brain activation. The mechanism of acupuncture at BL40 in regulating bladder function was explored by toluidine blue staining and enzyme-linked immunosorbent assay, and the mechanism was verified by stabilizing mast cells (MCs) or blocking tibial nerve. RESULTS: Deep acupuncture at BL40 significantly increased the intercontraction interval in OAB rats and enhanced the mean amplitude of low frequency fluctuation of primary motor cortex (M1), periaquaductal gray matter (PAG), and pontine micturition center (PMC). It also increased the zero-lag functional connectivity between M1 and PAG and between PAG and PMC. Shallow acupuncture at BL40 and acupuncture at non-acupoint or GB39 had no effect on these indexes. Further studies suggested that deep acupuncture at BL40 increased the number and degranulation rate of MCs as well as the contents of 5-hydroxytryptamine, substance P, and histamine in the tissues around BL40. Blocking the tibial nerve by lidocaine injection or inhibiting MC degranulation by sodium cromoglycate injection obstructed the effects of acupuncture on restoring urinary function and modulating brain activation in OAB rats. CONCLUSION Deep acupuncture at BL40 may be more effective for inhibiting OAB by promoting degranulation of MCs around the acupoint and stimulating tibial nerve, thereby regulating the activation of the brain area that controls the lower urinary tract. Please cite this article as: Liu X, Zhang CY, Du XY, Li SS, Wang YQ, Zheng Y, Deng HZ, Fang XQ, Li JY, Wang ZQ, Xu SF, Mi YQ. Acupuncture at Weizhong (BL40) attenuates acetic acid-induced overactive bladder in rats by regulating brain neural activity through the modulation of mast cells and tibial nerves. J Integr Med. 2025; 23(1): 46-55.
Animals ; Urinary Bladder, Overactive/physiopathology* ; Mast Cells/physiology* ; Rats, Sprague-Dawley ; Female ; Acupuncture Therapy ; Acupuncture Points ; Rats ; Brain/physiopathology* ; Tibial Nerve/physiopathology* ; Acetic Acid ; Urinary Bladder/physiopathology*