Objective To investigate the combined effect of berberine （BBR） and fluconazole （FLC） on FLC-tolerant Candida albicans in vitro. Methods The sensitivity of 8 strains of Candida albicans to FLC was assessed by determining their minimal inhibitory concentration （MIC） using broth microdilution method. FLC-tolerant strains were screened from FLC-sensitive strains by disk diffusion assay. The effect of BBR combined with FLC on FLC-tolerant Candida albicans was investigated by disk diffusion assay. Results All eight strains of Candida albicans exhibited sensitivity to FLC, with minimal inhibitory concentration （MIC₅₀） values below 0.5 μg/ml. Strains Y0109, 9821, 7879, 7654, and 9296 displayed colony growth in the inhibition zone after 48 h of constant temperature incubation, indicating FLC tolerance. When strains Y0109 and 9821 were subjected to a combination of BBR and FLC, the number of colonies within the inhibition zone decreased progressively with the increase of BBR concentration following a 48 h constant temperature culture. The inhibition zone became clear with the increasing of BBR concentration and increased with the increase of FLC loading, which showed a dose-dependent relationship. Conclusion The BBR combined with FLC demonstrated efficacy against FLC-tolerant strains.

Background/Aims: Dexamethasone (DEX) is a widely used exogenous therapeutic glucocorticoid in clinical settings. Its long-term use leads to many side effects. However, its effect on metabolic disorders in individuals on a high-fat diet (HFD) remains poorly understood. Methods: In this study, HFD-fed mice were intraperitoneally injected with DEX 2.5 mg/kg/day for 30 days. Lipid metabolism, adipocyte proliferation, and inflammation were assayed using typical approaches. Results: DEX increased the epididymal fat index and epididymal adipocyte size in HFD-fed mice. The number of epididymal adipocytes with diameters > 70 μm accounted for 0.5% of the cells in the control group, 30% of the cells in the DEX group, 19% of the cells in the HFD group, and 38% of all the cells in the D+H group. Adipocyte proliferation in the D+H group was inhibited by DEX treatment. Adipocyte enlargement in the D+H group was associated with increased the lipid accumulation but not the adipocyte proliferation. In contrast, the liver triglyceride and total cholesterol levels and their metabolism were downregulated by the same treatment, indicating the therapeutic potential of DEX for nonalcoholic fatty liver disease. Conclusions DEX synergizes with HFD to promote lipid deposition in adipose tissues. A high risk of obesity development in patients receiving HFD and DEX treatment is suggested.

The auxin/indole-3-acetic acid (Aux/IAA) gene family is an important regulator for plant growth hormone signaling, involved in plant growth, development, as well as response to environmental stresses. In the present study, we identified SmIAA7 which is potentially associated with Salvia miltiorrhiza leaf development through comparatively analyzed the transcriptome data from different pinnate leaves. SmIAA7 was successfully isolated from S. miltiorrhiza using the specific primers. Then subsequent bioinformatic analysis, prokaryotic expression and purification, subcellular localization, and induction expression analysis under auxin and abiotic stress were performed. The full-length of SmIAA7 contained an ORF of 684 bp encoding a protein of 227 amino acid with a molecular weight of 25.3 kD. Conserved domain analysis showed that SmIAA7 contains the conserved Aux_IAA domain (pfam02309). Sequence analysis and phylogenetic tree analysis results indicated SmIAA7 was phylogenetically close to IAA7 and IAA14 from other plants, suggesting SmIAA7 involved in plant growth and development as well as response to environmental stresses. The prokaryotic expression vector pET28a-SmIAA7 was constructed and SmIAA7 recombinant protein was successfully expressed in E. coli Rosetta (DE3) strain. Subcellular localization experiment demonstrated that SmIAA7 localized in the nucleus of plant cells. Real-time fluorescence quantitative PCR results showed that the expression level of SmIAA7 was upregulated in response to auxin. Drought, low temperature, and salt stress significantly increased the transcript level of SmIAA7 gene. This study lays a foundation for further elucidating the role of SmIAA7 in leaf development, signal transduction, and stress defense in S. miltiorrhiza.

Emodin is a hydroxyanthraquinone compound that is widely distributed and has multiple pharmacological activities, including anti-diarrheal, anti-inflammatory, and liver-protective effects. Research indicates that emodin may be one of the main components responsible for inducing hepatotoxicity. However, studies on the mechanisms of liver injury are relatively limited, particularly those related to bile acids(BAs) metabolism. This study aims to systematically investigate the effects of different dosages of emodin on BAs metabolism, providing a basis for the safe clinical use of traditional Chinese medicine(TCM)containing emodin. First, this study evaluated the safety of repeated administration of different dosages of emodin over a 5-week period, with a particular focus on its impact on the liver. Next, the composition and content of BAs in serum and liver were analyzed. Subsequently, qRT-PCR was used to detect the mRNA expression of nuclear receptors and transporters related to BAs metabolism. The results showed that 1 g·kg~(-1) emodin induced hepatic damage, with bile duct hyperplasia as the primary pathological manifestation. It significantly increased the levels of various BAs in the serum and primary BAs(including taurine-conjugated and free BAs) in the liver. Additionally, it downregulated the mRNA expression of farnesoid X receptor(FXR), retinoid X receptor(RXR), and sodium taurocholate cotransporting polypeptide(NTCP), and upregulated the mRNA expression of cholesterol 7α-hydroxylase(CYP7A1) in the liver. Although 0.01 g·kg~(-1) and 0.03 g·kg~(-1) emodin did not induce obvious liver injury, they significantly increased the level of taurine-conjugated BAs in the liver, suggesting a potential interference with BAs homeostasis. In conclusion, 1 g·kg~(-1) emodin may promote the production of primary BAs in the liver by affecting the FXR-RXR-CYP7A1 pathway, inhibit NTCP expression, and reduce BA reabsorption in the liver, resulting in BA accumulation in the peripheral blood. This disruption of BA homeostasis leads to liver injury. Even doses of emodin close to the clinical dose can also have a certain effect on the homeostasis of BAs. Therefore, when using traditional Chinese medicine or formulas containing emodin in clinical practice, it is necessary to regularly monitor liver function indicators and closely monitor the risk of drug-induced liver injury.
Emodin/administration & dosage* ; Bile Acids and Salts/metabolism* ; Animals ; Male ; Liver/injuries* ; Chemical and Drug Induced Liver Injury/genetics* ; Drugs, Chinese Herbal/adverse effects* ; Humans ; Rats, Sprague-Dawley ; Mice ; Rats

Based on the α7 nicotinic acetylcholine receptor(α7nAChR), this study examined how tetrahydropalmatine(THP) affected BV2 microglia exposed to lipopolysaccharide(LPS), aiming to clarify the possible mechanism underlying the anti-depression effect of THP from the perspectives of preventing inflammation and regulating polarization. First, after molecular docking and determination of the content of Corydalis saxicola Bunting total alkaloids, THP was initially identified as a possible anti-depression component. The BV2 microglia model of inflammation was established with LPS. BV2 microglia were allocated into a normal group, a model group, low-and high-dose(20 and 40 μmol·L~(-1), respectively) THP groups, and a THP(20 μmol·L~(-1))+α7nAChR-specific antagonist MLA(1 μmol·L~(-1)) group. The CCK-8 assay was used to screen the safe concentration of THP. A light microscope was used to examine the morphology of the cells. Western blot and immunofluorescence were used to determine the expression of α7nAChR. qRT-PCR was performed to determine the mRNA levels of inducible nitric oxide synthase(iNOS), cluster of differentiation 86(CD86), suppressor of cytokine signaling 3(SOCS3), arginase-1(Arg-1), cluster of differentiation 206(CD206), tumor necrosis factor(TNF)-α, interleukin(IL)-6, and IL-1β. Enzyme-linked immunosorbent assay(ELISA) was employed to measure the levels of TNF-α, IL-6, and IL-1β in the cell supernatant. The experimental results showed that THP at concentrations of 40 μmol·L~(-1) and below had no effect on BV2 microglia. THP improved the morphology of BV2 microglia, significantly up-regulated the protein level of α7nAChR, significantly down-regulated the mRNA levels of iNOS, CD86, SOCS3, TNF-α, IL-6, and IL-1β, significantly up-regulated the mRNA levels of Arg-1 and CD206, and dramatically lowered the levels of TNF-α, IL-6, and IL-1β in the cell supernatant. However, the antagonist MLA abolished the above-mentioned ameliorative effects of THP on LPS-treated BV2 microglia. As demonstrated by the aforementioned findings, THP protected LPS-treated BV2 microglia by regulating the M1/M2 polarization and preventing inflammation, which might be connected to the regulation of α7nAChR on BV2 microglia.
Berberine Alkaloids/chemistry* ; alpha7 Nicotinic Acetylcholine Receptor/chemistry* ; Microglia/metabolism* ; Mice ; Animals ; Cell Line ; Corydalis/chemistry* ; Humans ; Molecular Docking Simulation ; Inflammation/drug therapy* ; Nitric Oxide Synthase Type II/immunology* ; Tumor Necrosis Factor-alpha/immunology*

As a new type of production factor that can empower the development of new quality productivity, the data element is an important engine to promote the high quality development of the industry. Traditional Chinese medicine(TCM) dispensing is the most basic work of TCM clinical pharmacy, and its quality directly affects the clinical efficacy of TCM. The integration of data elements and TCM dispensing can stimulate the innovation and vitality of the TCM dispensing industry and promote the high-quality and sustainable development of the industry. A large-scale, detailed, and systematic study on TCM dispensing was conducted. The innovative practice path of data fusion construction in the whole process of TCM dispensing was investigated by integrating the digital resources "nine full activities" of TCM dispensing, creating the digital dictionary of "TCM clinical information data elements", and exploring innovative applications of TCM dispensing driven by data and technology, so as to promote the standardized, digital, and intelligent development of TCM dispensing in medical health services. The research content of this project was successfully selected as the second batch of "Data element×" typical cases of National Data Administration in 2024, which is the only selected case in the field of TCM.
Medicine, Chinese Traditional/methods* ; Drugs, Chinese Herbal ; Humans

OBJECTIVE: Varied acupoint selections represent a potential cause of the uncertainty surrounding the efficacy of acupuncture for knee osteoarthritis (OA). Skin temperature, a guiding factor for acupoint selection, may help to address this issue. This study explored thermal sensitization of acupoints used for the treatment of knee OA. METHODS: This cross-sectional case-control study enrolled cases aged 45-75 years with symptomatic knee OA and age- and gender-matched non-knee OA controls in a 1:1 ratio. All participants underwent infrared thermographic imaging. The primary outcome was the relative skin temperature of acupoint (STA), and the secondary outcome was the absolute STA of 11 acupoints. The Z test was used to compare the relative and absolute STAs between the groups. Principal component analysis was used to extract the common factors (CFs, acupoint cluster) in the STAs. A general linear model was used to identify factors affecting the STA in the knee OA cases. For the group comparisons of relative STA, P < 0.0045 (adjusted for 11 acupoints through Bonferroni correction) was considered to indicate statistical significance. For other analyses, P < 0.05 was used as the threshold for statistical significance. RESULTS: The analysis included 308 participants, consisting of 151 cases (mean age: [64.58 ± 6.67] years; male: 25.83%; mean body mass index: [25.70 ± 3.16] kg/m²) and 157 controls (mean age: [63.37 ± 5.96] years; male: 26.11%; mean body mass index: [24.47 ± 2.84] kg/m²). The relative STAs of ST34 (P = 0.0001), EX-LE2 (P < 0.0001), EX-LE5 (P = 0.0006), SP10 (P < 0.0001), BL40 (P = 0.0012) and GB39 (P = 0.0037) were higher in the knee OA group. No difference was found in the STAs of ST35, ST36, SP9, GB33 and GB34. Four CFs were identified for relative STA in both groups. The acupoints within each CF were consistent between the groups. The mean values of the relative STAs across each CF were higher in the knee OA group. In the knee OA cases, no factors were observed to affect the relative STA, while age and gender were found to affect the absolute STA. CONCLUSION Among patients with knee OA, thermal sensitization occurs in the acupoints of the lower extremity, exhibiting localized and regional thermal consistencies. The thermally sensitized acupoints that we identified in this study, ST34, SP10, EX-LE2, EX-LE5, GB39 and BL40, may be good choices for the acupuncture treatment of knee OA. Please cite this article as: Tu JF, Wang XZ, Yan SY, Wang YR, Yang JW, Shi GX, Zhang WZ, Jing LN, Yang LS, Liu DH, Wang LQ, Mi BH. Thermal sensitization of acupoints in patients with knee osteoarthritis: A cross-sectional case-control study. J Integr Med. 2025; 23(3): 289-296.
Humans ; Osteoarthritis, Knee/physiopathology* ; Male ; Cross-Sectional Studies ; Middle Aged ; Female ; Acupuncture Points ; Case-Control Studies ; Aged ; Skin Temperature ; Acupuncture Therapy

Objective To explore the injury process of retinal ganglion cells(RGCs)after glucocorticoid(GC)-in-duced ocular hypertension(OHT),as well as the protective effect and mechanism of estradiol(E2)in RGC injury in rats with OHT.Methods Atotalof36(36 eyes)12-week-old male Sprague-Dawley(SD)rats were randomly divided into the blank control group,the GC-OHT group,and the OHT-E2 group,with 12 rats in each group.Rats in the GC-OHT group and the OHT-E2 group were subconjunctivally injected with GC,while those in the blank control group were subconjuncti-vally injected with an equal volume of normal saline.Two weeks after modeling,in addition to being injected with GC,rats in the OHT-E2 group were also provided with E2 eye drops.Before modeling and 1,2,3,and 4 weeks after modeling,the intraocular pressure of rats in each group was measured.The visual acuity changes of rats in each group were detected by pattern electroretinogram(P-ERG)and flash visual evoked potential(F-VEP)4 weeks after modeling.After the eyeballs were removed,the distribution and number of RGCs in rats of each group were observed by immunofluorescence staining.Immunohistochemistry,Western blot,and real-time fluorescence-based quantitative polymerase chain reaction were used to detect the relative protein and mRNA expression levels of NOD-like receptor protein 3(NLRP3),cysteine aspartate prote-ase-1(Caspase-1),and gasdermin-D(GSDMD)in rats in each group.Results There was no statistically significant difference in the intraocular pressure of rats in each group before modeling(P＞0.05).Compared with the blank control group,the intraocular pressure of rats in the GC-OHT group increased 1,2,3,and 4 weeks after modeling,and the differ-ences were all statistically significant(all P＜0.01).Compared with the GC-OHT group,the intraocular pressure of rats in the OHT-E2 group decreased 3 and 4 weeks after modeling,and the differences were all statistically significant(all P＜0.01).The P-ERG and F-VEP results showed that compared with the blank control group,the amplitudes of P50 and P1 waves of rats in the GC-OHT group decreased,and the differences were both statistically significant(both P＜0.05).Com-pared with the GC-OHT group,the amplitudes of P50 and Pl waves of rats in the OHT-E2 group increased,and the differ-ences were both statistically significant(both P＜0.05).The immunofluorescence staining results showed that compared with the blank control group,the number of RGCs of rats in the GC-OHT group decreased,and the difference was statisti-cally significant(P＜0.001).Compared with the GC-OHT group,the number of RGCs of rats in the OHT-E2 group in-creased,and the difference was statistically significant(P＜0.001).The results of immunohistochemistry,Western blot,and real-time fluorescence-based quantitative polymerase chain reaction showed that compared with the blank control group,the relative protein and mRNA expression levels of NLRP3,Caspase-1,and GSDMD in the retina of rats in the GC-OHT group all increased,and the differences were all statistically significant(all P＜0.05).Compared with the GC-OHT group,the relative protein and mRNA expression levels of NLRP3,Caspase-1,and GSDMD in the retina of rats in the OHT-E2 group all decreased,and the differences were all statistically significant(all P＜0.01).Conclusion GC-induced OHT can cause pyroptosis of RGCs,and E2 may alleviate the injury of RGCs in rats with OHT by inhibiting the pyroptosis-related NLRP3/Caspase-1/GSDMD signaling pathway.

Objective:To observe the efficacy of probiotics in the adjuvant treatment of bronchial asthma and to explore the relationship between their action and intestinal flora.Methods:A total of 76 newly diagnosed patients with mild-to-moderate bronchial asthma treated at Baotou Central Hospital between November 2023 and January 2025 were randomly divided into two groups:the conventional treatment group(n=38)and the combined probiotic treatment group(n=38).Post-treatment comparisons were made between the two groups regarding symptom resolution time,Asthma Control Test(ACT)scores,lung function,fractional exhaled nitric oxide(FeNO)levels,serum inflammatory cytokines,complement levels,and other indicators.Faecal samples were collected for 16S rDNA sequencing of gut microbiota.Results:Baseline characteristics showed no significant differences between the two groups(P＞0.05).Compared to the conventional treatment group,the combined probiotic group exhibited significantly shorter resolution times for asthma symptoms and lung rales(P＜0.001),significantly higher ACT scores,FEV1,and PEF(P＜0.001),and significantly lower FeNO levels(P＜0.001).Additionally,serum interleukin-6(IL-6),tumor necrosis factor-α(TNF-α),and complement C3 levels were significantly reduced(P＜0.001),while serum interleukin-6(IL-10)levels were significantly increased(P＜0.001).16S rDNA sequencing revealed no significant changes in gut microbiota richness or diversity in the conventional treatment group before and after treatment(P＞0.05),whereas intestinal flora richness and diversity were significantly increased in the combined probiotic treatment group compared to the pre-treatment group(P＜0.05).Correlation analysis between gut microbiota and inflammatory markers demonstrated that Faecalibacterium and Bifidobacterium abundance were negatively correlated with TNF-α levels(P＜0.05),while Escherichia-Shigella,and Streptococcus abundance were positively correlated with TNF-α levels(P＜0.05).Streptococcus and Klebsiella abundance were positively correlated with IL-6 levels(P＜0.05).Escherichia-Shigella and Streptococcus abundance were negatively correlated with IL-10 levels and positively correlated with complement C3 levels(P＜0.05).Conclusion:Probiotics may assist in improving bronchial asthma symptoms by influencing the gut flora to reduce the inflammatory response.

Objective:To investigate the predictive value of circulating free DNA(cfDNA)combined with interleukin 10(IL-10)in predicting central nervous system infiltration(CNSI)in diffuse large B-cell lymphoma(DLBCL).Methods:The clinical data of 63 patients with DLBCL in our hospital from May 2021 to April 2023 were retrospectively analyzed.The 63 patients were divided into CNSI group(15 cases)and non-CNSI group(48 cases)base on whether CNSI occurred.The age,sex,Ann Arbor stage,ECOG score,IPI risk,CNS-IPI risk,number of extranodal sites involved,bone marrow involvement,hypertrophic disease,B symptoms,source cells,glucose quantification,Pandy test,cerebrospinal fluid(CSF)chlorine,CSF nucleated cell count,CSF protein,peripheral blood cfDNA,and IL-10 status were compared between the two groups.The correlation between cfDNA,IL-10 in peripheral blood and CSF protein was analyzed by Pearson correlation analysis.Receiver operating characteristic(ROC)curve was used to analyze the predictive value of peripheral blood cfDNA and IL-10 on secondary CNSI in DLBCL patients.The last follow-up was on November 30,2023.Kaplan-Meier method was used to calculate the time of secondary CNSI in the non-CNSI group.Results:The IPI risk,CNS-IPI risk,number of extranodal sites involved,and CSF protein in the CNSI group were significantly higher than those in the non-CNSI group(all P＜0.05).The levels of cfDNA and IL-10 in peripheral blood of CNSI group were significantly higher than those of non-CNSI group(both P＜0.01).cfDNA and IL-10 in peripheral blood were both positively correlated with CSF protein(r=0.402 4,0.315 1).ROC curve analysis showed that peripheral blood cfDNA and IL-10 had certain predictive value for CNSI,and the area under the curve(AUC)was 0.829 and 0.742,respectively.The AUC of the combined detection was 0.910,with a sensitivity of 80.00％and a specificity of 93.70％.The diagnostic efficacy was significantly higher than that of the two prediction values alone.The median follow-up time was 20(6-31)months.Non-CNSI patients were grouped based on peripheral blood cfDNA combined with IL-10 positive or negative pairs.The time of secondary CNSI in positive group was significantly shorter than that in negative group(P＜0.05).Conclusion:cfDNA and IL-10 in peripheral blood of DLBCL patients with CNSI are significantly increased,and the combined detection of cfDNA and IL-10 has good predictive value for CNSI.