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.

ObjectiveBased on ultra-high performance liquid chromatography-quadrupole-time-of-flight mass spectrometry（UPLC-Q-TOF-MS/MS）， network pharmacology and molecular docking techniques， to explore the pharmacodynamic material basis and mechanism of Renshen Wuweizi Tang in treating spleen-lung Qi deficiency syndrome. MethodsThe chemical components in the decoction of Renshen Wuweizi Tang were systematically characterized and identified by UPLC-Q-TOF-MS/MS， and network pharmacology was used to screen potential active ingredients， collect component targets and gene sets related to spleen-lung Qi deficiency syndrome， and obtain protein interaction relationships through STRING. Cytoscape 3.9.1 was used to construct a "formula-syndrome" association network and calculate topological feature values. Gene ontology（GO） function and Kyoto Encyclopedia of Genes and Genomes（KEGG） pathway enrichment analysis were performed on core genes to explore potential pharmacodynamic links， the average shortest path between the formula-drug target network and the pharmacodynamic link gene network was calculated to discover dominant pharmacodynamic links， and MCODE plugin was used to identify core gene clusters from the dominant pharmacodynamic links， which were validated using Gene Expression Omnibus（GEO）， and molecular docking was performed between key components and core targets. ResultsOne hundred and thirty-seven components were identified in the negative ion mode， and eighty components were identified in the positive ion mode. After deduplication， a total of 185 components were identified， mainly composed of triterpenoid saponins（49） and flavonoids（54）. Based on the "formula-syndrome" correlation network analysis， energy metabolism was determined to be the dominant pharmacodynamic link of Renshen Wuweizi Tang in the treatment of spleen-lung Qi deficiency syndrome. The results of molecular docking showed that 7 components（adenosine， atractylenolide Ⅱ， atractylenolide Ⅲ， ginsenoside Rg₁， glycyrrhizin B₂， glycyrrhizin E₂ and campesterol） from 4 medicinal materials（Ginseng Radix et Rhizoma， Atractylodis Macrocephalae Rhizoma， Glycyrrhizae Radix et Rhizoma and Poria） in this formula might regulate energy metabolism by acting on 6 targets， namely cyclic adenosine monophosphate-response element binding protein 1（CREB1）， glyceraldehyde-3-phosphate dehydrogenase（GAPDH）， interleukin（IL）-6， nuclear transcription factor（NF）-κB1， peroxisome proliferator-activated receptor α（PPARα）， and tumor necrosis factor（TNF）， thus improving the symptoms of diseases related to spleen-lung Qi deficiency syndrome. ConclusionThis study established a UPLC-Q-TOF-MS/MS for rapid characterization and identification of chemical components in the decoction of Renshen Wuweizi Tang， expanding the understanding of the material composition of this formula， and found that 7 components might act on the key advantageous pharmacodynamic link "energy metabolism" through 6 targets to improve the related symptoms of spleen-lung Qi deficiency syndrome. This can provide a reference for the subsequent exploration of the material benchmark and mechanism of the famous classical formula.

Interactions between brain-resident and peripheral infiltrated immune cells are thought to contribute to neuroplasticity after cerebral ischemia. However, conventional bulk sequencing makes it challenging to depict this complex immune network. Using single-cell RNA sequencing, we mapped compositional and transcriptional features of peri-infarct immune cells. Microglia were the predominant cell type in the peri-infarct region, displaying a more diverse activation pattern than the typical pro- and anti-inflammatory state, with axon tract-associated microglia (ATMs) being associated with neuronal regeneration. Trajectory inference suggested that infiltrated monocyte-derived macrophages (MDMs) exhibited a gradual fate trajectory transition to activated MDMs. Inter-cellular crosstalk between MDMs and microglia orchestrated anti-inflammatory and repair-promoting microglia phenotypes and promoted post-stroke neurogenesis, with SOX2 and related Akt/CREB signaling as the underlying mechanisms. This description of the brain's immune landscape and its relationship with neurogenesis provides new insight into promoting neural repair by regulating neuroinflammatory responses.
Humans ; Ischemic Stroke ; Brain/metabolism* ; Macrophages ; Brain Ischemia/metabolism* ; Microglia/metabolism* ; Gene Expression Profiling ; Anti-Inflammatory Agents ; Neuronal Plasticity/physiology* ; Infarction/metabolism*

Objective To investigate the anti-inflammatory effects of Bupi Yichang Pills on mice with experimental colitis and its potential mechanism of action.Methods Dextran sulfate sodium(DSS)was used to model the experimental colitis,and low-,medium-and high-doses of Bupi Yichang Pills(1.5,3.0,6.0 g·kg-1·d-1)and Mesalazine(300 mg·kg-1·d-1)were fed at the same time.Mice were observed for general behavior and weighed.Hematoxylin-eosin staining was used to observe the pathological injury of colonic tissues.qPCR and ELISA were used to detect the levels of inflammatory cytokines(TNF-α,IL-1β,IL-6,IL-10,IL-35 and TGF-β1),qPCR and Western Blot were used to detect the mRNA and protein levels of glucose transporters and glycolytic kinases.Results Low-,medium-and high-doses of Bupi Yichang Pills significantly down-regulated disease activity index in colitis mice(P＜0.05,P＜0.01).The body mass and colon length were significantly increased,while colon mass,colon mass index and unit colon mass index were significantly reduced(P＜0.05,P＜0.01),and ulcer formation and inflammatory cell infiltration in colonic tissue were significantly improved.In addition,medium-and high-doses of Bupi Yichang Pills significantly down-regulated the mRNA levels and concentrations of pro-inflammatory cytokines including TNF-α,IL-1β and IL-6(P＜0.01),while significantly up-regulated the mRNA levels and concentrations of anti-inflammatory cytokines such as IL-10,IL-35 and TGF-β1(P＜0.01).We further found that high-dose of Bupi Yichang Pills significantly down-regulated the mRNA and protein expressions of glucose transporters(Glut1,Glut2,Glut4)and glycolytic kinases(HK2,Aldolase A,PKM2)in colonic tissue(P＜0.01).Conclusions Bupi Yichang Pills effectively alleviates DSS-induced experimental colitis,and its specific mechanism of action is related to the improvement of glycolytic metabolic pathways and the regulation of inflammatory cytokine expression.

Objective To detect the levels of anti-soluble liver antigen(anti-SLA)antibodies in the serum of patients with autoim-mune hepatitis(AIH)and analyze their value in liver injury.Methods A retrospective analysis was conducted on 33 AIH patients with anti-SLA antibody-positive and 33 age-and sex-matched anti-SLA antibody-negative AIH cases diagnosed at Nanjing Second Hos-pital from January 2017 to April 2024.The general and clinical data of the patients were collected along with the detection of anti-SLA antibody(by protein immunoblotting),anti-nuclear antibodies(by indirect immunofluorescence)and other autoimmune liver disease-related autoantibodies,the biochemical parameters,e.g.,total bilirubin(T-Bil),alanine aminotransferase(ALT),aspartate amin-otransferase(AST),gamma-glutamyl transferase(GGT),alkaline phosphatase(ALP),and the level of immunoglobulin IgG.The clinical characteristics,laboratory parameters,and liver histopathological features of the patients were analyzed and compared.Results There were no statistically significant differences were observed in gender,age,autoimmune liver disease-related antibodies(such as antinuclear antibody,anti-smooth muscle antibody,etc.)and liver function parameters(AST,ALT,GGT and ALP),between the two groups of patients(P＞0.05).However,in the patients with positive anti-SLA antibodies,the levels of T-Bil and IgG in serum were significantly higher than those of the negative group with both P value less than 0.05(P values of 0.017 and 0.048,respectively).The pathological examination for liver tissue revealed that the proportion of the patients with lymphocyte-plasma cell infiltration in anti-SLA-positive group was significantly higher than that in anti-SLA-negative group(χ2=4.243,P＜0.05),suggesting more active immune re-sponse.Conclusion The detection of anti-SLA antibodies levels in the serum of AIH patients may reflect the extent of liver injury,and should have the potential for assisting diagnosis and monitoring the disease condition.

Cardiovascular surgery is still the preferred treatment for some congenital or acquired cardiovascular diseases.With the aging of China's population and the prevalence of unhealthy lifestyles brought about by the improvement of living standards,the burden of cardiovascular diseases is still steadily increasing and the volume of cardiovascular surgery continues to be at a high level,which puts forward a new demand for the prevention and treatment strategy of cardiovascular diseases and the allocation of medical resources.Cardiovascular surgery has many perioperative complications and high risk of mortality,a scientific surgical complexity scoring system can help clinicians fully assess the difficulty of surgery,stratify the risk of patient surgery,and formulate targeted and personalized diagnosis and treatment plans;meanwhile,it can help the health management department accurately grasp the overall diagnosis and treatment level of China's cardiovascular surgery,monitor the quality of medical care and provide a reference for the formulation and implementation of relevant medical policies.In this study,we systematically review the current status of evidence-based research on different cardiovascular surgical complexity assessment systems and summarize the application of machine learning in cardiovascular surgical assessment,with a view to contributing to the establishment of a cardiovascular surgical complexity assessment system applicable to the Chinese population.

Tuberculosis is caused by Mycobacterium tuberculosis,and the problem of its drug resistance has become increasingly prominent in recent years,attracting widespread attention globally.Currently,the situation of drug-resistant tuberculosis is grim,and effective strategies are urgently needed to deal with it.Understanding the drug resistance mechanism and treatment status of drug-resistant tuberculosis can provide an important basis for clinical prevention and treatment of drug-resistant tuberculosis.This paper reviews the progress of drug resistance mechanism and treatment of drug-resistant tuberculosis,in order to provide a reference for clinical intervention.

Objective To investigate the correlation between TCM syndrome types and solar term of onset in patients with gastric cancer.Methods A total of 359 patients with gastric cancer admitted to the Cancer Center of the First Affiliated Hospital of Guangzhou University of Chinese Medicine from January 2020 to August 2023 were included in this study,and the frequency distribution method was used to analyze their information such as sex,age,solar term of onset,differentiation,metastasis and TCM syndrome type.The solar term of onset corresponding to the onset date was calculated,and then the association between solar term of onset and TCM syndrome type in gastric cancer was analyzed.The circular distribution method was used to explore the peak of solar term of onset and TCM syndrome type.Results Among the 359 patients with gastric cancer included in this study,male patients were more than female patients(1.69∶1).The age of onset was mainly between 60 and 70 years old(117 cases,32.6%),and male patients(85 cases,72.6%)were more than female patients(32 cases,27.3%)in this age group.The most common TCM syndromes were qi and blood deficiency syndrome(160 cases,44.6%)and phlegm damp condensation syndrome(94 cases,26.2%).The onset of the disease mainly occurred in winter(132 cases,36.8%),and the peaks were light snow(31 cases,23.5%),major cold(25 cases,18.9%),heavy snow(23 cases,17.4%)and the start of winter(22 cases,16.7%).Qi and blood deficiency syndrome and phlegm damp condensation syndrome in patients with gastric cancer were correlated with solar terms and seasons(P<0.05).The 285 patients with gastric cancer were mainly poorly differentiated gastric cancer(175 cases,61.4%),mainly concentrated in winter(66 cases,37.7%).The main route of gastric cancer metastasis is lymph node metastasis,followed by liver and abdominal cavity metastasis.Conclusion Qi and blood deficiency syndrome and phlegm dampness condensation syndrome are common in patients with gastric cancer.The onset time of gastric cancer is mostly in winter,and the syndrome type is significantly correlated with the onset solar term and differentiation degree.

Objective To investigate the regulatory effect of Bupi Yichang pill(BPYCP)on CD4+T cell subsets of ulcerative colitis(UC)mice.Methods Forty-eight C57BL/6 mice were randomly divided into 4 groups:the control group(n=10),the model group(DSS group,n=13),the model +BPYCP group(DSS+BPYCP group,n=13)and the model+ mesalazine(5-ASA)group(DSS+5-ASA group,n=12).The mouse UC model was induced by 2.5%dextrosan sulfate(DSS)solution.The DSS+BPYCP group and the DSS+5-ASA group were given BPYCP or 5-ASA for 2 weeks,respectively,and fecal viscosity and blood in stool were observed.The colon length was measured.Colonic mass index and unit colonic mass index were calculated.Hematoxylin-eosin(HE)staining was used to observe pathological changes of colon and to score the pathological tissue damage.The level of CD4+T cell subsets in mesenteric lymph nodes was detected by flow cytometry.The expression levels of cytokines interferon-γ(INF-γ),interleukin(IL-4),IL-17A,IL-10 and IL-21 secreted by CD4+T cell subsets in colon tissue were detected by ELISA.Real-time fluorescence quantitative PCR was used to detect colon tissue CD4+T cell subset nuclear transcription factors,mRNA expression levels of T-frame protein 21(T-bet),GatA-binding protein 3(GATA-3),retinoa-associated nuclear orphan receptor γt(RORγt),B cell lymphoma-6(Bcl-6)and Foxp3 in rats.Results Compared with the DSS group,the diarrhea and hematostoecium symptoms of UC mice in the DSS+BPYCP group and the DSS+5-ASA group were significantly improved,body weight and colon length of mice were increased,and colon mass,colon mass index and unit colon mass index were decreased(P＜0.05).The mucosal epithelium was more complete than that in the DSS group,and gland arrangement was more regular.The inflammatory cell infiltration was less,and the pathological tissue damage score was significantly decreased(P＜0.01).The proportion of Th2 cells in mesenteric lymph nodes was decreased,the proportion of Th17 cells and the level of IL-17A were decreased,and the mRNA levels of T-bet,GATA-3,RORγt and Bcl-6 in colon tissue were decreased(P＜0.05).In the DSS+BPYCP group,the proportion of Th1 cells decreased,the proportion of CD4+CD25+Treg cells,CD4+CD25+Foxp3+Treg cells and the level of IL-10 increased,and the proportion of CD4+CXCR5+Tfh cells and the level of IL-21 decreased.The level of Foxp3 mRNA increased(P＜0.05).The proportion of Th1 cells and the level of IFN-γ were decreased in the DSS+5-ASA group(P＜0.05).Conclusion BPYCP may alleviate UC by remodeling the homeostasis of CD4+T cell subpopulations.

【Objective】 To analyze the distribution of unexpected antibodies in tumor patients retrospectively and explore the clinical significance. 【Methods】 Unexpected antibody screening was performed on inpatients with blood preparation and blood transfusion in our hospital from January 2004 to December 2022, with 1 176 cases tested positive, and the types of unexpected antibodies and distribution characteristics were statistically analyzed. 【Results】 Unexpected antibodies were screened in 1 176 cases, with the positive rate at 1.05% (1 176/111 483). The unexpected antibodies were mainly anti-E 16.33%(192/1 176), anti-M 7.99% (94/1 176), anti-Mur 5.70% (67/1 176) and anti-Le^a 4.76% (56/1 176). Among the 1 176 cases, gastrointestinal tumors accounted for 27.99% (329/1 176), gynecological tumors accounted for 24.84% (292/1 176), respiratory tumors accounted for 16.67% (196/1 176) . 【Conclusion】 The influencing factors of unexpected antibodies in tumor patients were disease type, blood transfusion history and blood type. Therefore, it is necessary for clinical departments to carry out unexpected antibody screening and perform Rh blood type matched transfusion for tumor patients to avoid alloantibody production.