ObjectiveTo investigate the ability of clinically isolated， Helicobacter pylori （H. pylori）-specific gene polymerase chain reaction （PCR）-positive gastric， vaginal， and fecal Candida to release H. pylori. MethodsResuscitate 4 strains of H. pylori -specific 16S rDNA and ureA gene PCR-positive Candida strains isolated in laboratory from clinical sources， including 1 strain of gastric Candida， 1 strain of fecal Candida， 2 strains of vaginal Candida and the standard Candida albicans strain ATCC10231 （Ca10231）. The presence of H. pylori-specific ureA in the 5 strains of Candida isolates was confirmed by PCR. The aforementioned strains of Candida and H.pylori were inoculated into urea medium and cultured in a constant temperature incubator at 37 ℃. The color change of the medium was observed daily. A change in the medium's color from yellow to red indicated the presence of urease activity. Then， the five strains of Candida and H. pylori were co-incubated with the magnetic beads coated with H. pylori antibodies respectively. Scanning electron microscopy （SEM） was employed to observe the presence of bacilli adsorbed on the surface of the magnetic beads. PCR was used to detect the presence of H.pylori-specific 16S rDNA and ureA genes on magnetic beads. ResultsThe PCR analysis of the ureA gene in the four Candida isolates was positive， whereas the Ca10231 strain tested negative. Upon culturing the four Candida isolates on urea medium， the medium color changed from yellow to red which was determined to be urease positive， while the medium containing Ca10231 remained unchanged， which was urease negative. SEM revealed that bacilli could be observed on the surface of magnetic beads co-incubated with the 4 strains of Candida of clinical origin and H.pylori isolate. Specifically， PCR testing of the magnetic beads co-incubated with one vaginal Candida， one gastric Candida and H.pylori isolate showed positive results for the 16S rDNA and ureA genes of H. pylori； however， the PCR tests for the two genes were negative for the magnetic beads co-incubated with the other two Candida isolate. ConclusionThis study demonstrates that H. pylori-specific genes Candida can release H. pylori.

Mycophenolic acid (MPA), the active moiety of both mycophenolate mofetil (MMF) and enteric-coated mycophenolate sodium (EC-MPS), serves as a primary immunosuppressant for maintaining solid organ transplants. Therapeutic drug monitoring (TDM) enhances treatment outcomes through tailored approaches. This study aimed to develop an evidence-based guideline for MPA TDM, facilitating its rational application in clinical settings. The guideline plan was drawn from the Institute of Medicine and World Health Organization (WHO) guidelines. Using the Delphi method, clinical questions and outcome indicators were generated. Systematic reviews, Grading of Recommendations Assessment, Development, and Evaluation (GRADE) evidence quality evaluations, expert opinions, and patient values guided evidence-based suggestions for the guideline. External reviews further refined the recommendations. The guideline for the TDM of MPA (IPGRP-2020CN099) consists of four sections and 16 recommendations encompassing target populations, monitoring strategies, dosage regimens, and influencing factors. High-risk populations, timing of TDM, area under the curve (AUC) versus trough concentration (C₀), target concentration ranges, monitoring frequency, and analytical methods are addressed. Formulation-specific recommendations, initial dosage regimens, populations with unique considerations, pharmacokinetic-informed dosing, body weight factors, pharmacogenetics, and drug‍-‍drug interactions are covered. The evidence-based guideline offers a comprehensive recommendation for solid organ transplant recipients undergoing MPA therapy, promoting standardization of MPA TDM, and enhancing treatment efficacy and safety.
Mycophenolic Acid/administration & dosage* ; Drug Monitoring/methods* ; Humans ; Organ Transplantation ; Immunosuppressive Agents/administration & dosage* ; Delphi Technique

eIF3a is a N ⁶-methyladenosine (m⁶A) reader that regulates mRNA translation by recognizing m⁶A modifications of these mRNAs. It has been suggested that eIF3a may play an important role in regulating translation initiation via m⁶A during infection when canonical cap-dependent initiation is inhibited. However, the death of animal model studies impedes our understanding of the functional significance of eIF3a in immunity and regulation in vivo. In this study, we investigated the in vivo function of eIF3a using eIF3a knockout and knockdown mouse models and found that eIF3a deficiency resulted in splenic tissue structural disruption and multi-organ damage, which contributed to severe sepsis induced by Lipopolysaccharide (LPS). Ectopic eIF3a overexpression in the eIF3a knockdown mice rescued mice from LPS-induced severe sepsis. We further showed that eIF3a maintains a functional and healthy immune system by regulating B cell function and quantity through m⁶A modification of mRNAs. These findings unveil a novel mechanism underlying sepsis, implicating the pivotal role of B cells in this complex disease process regulated by eIF3a. Furthermore, eIF3a may be used to develop a potential strategy for treating sepsis.

Objective To investigate the five-circuit and six-qi features at conception and at birth in the patients with endometrial cancer.Methods From June 2020 to August 2024,the information about the conception time and birth time of 1 099 patients with endometrial cancer admitted to Guang'anmen Hospital of China Academy of Chinese Medical Sciences was collected from the electronic medical record system.The circuit-qi information at conception and at birth of the patients was statistically analyzed,and then the congenital endowment characteristics of the patients were explored.Results The results showed that most of the patients suffering endometrial cancer were born in winter,and the dominant qi at birth of the patients was predominated by taiyang cold-water,and the differences of the distribution of dominant qi at birth were statistically significant(P＜0.05).There were no significant differences in the distribution of yearly circuit,guest qi,and sitian-zaiquan at birth,and in the distribution of seasons,yearly circuit,dominant qi,guest qi,and sitian-zaiquan at conception(P＞0.05),and only an obvious trend of differences was presented.Conclusion There is a certain correlation between the prevalence of endometrial cancer and the five-circuit and six-qi features at conception and at birth.The congenital endowment of patients with endometrial cancer is characterized by yang deficiency with predominant coldness,and the prevalence is related to jueyin wind wood.

Objective To investigate traditional Chinese medicine(TCM)syndrome characteristics associated with immunotherapy efficacy in cervical cancer using propensity score matching(PSM),aiming to identify the population benefiting from immunotherapy.Methods A retrospective analysis was conducted in 253 cervical cancer patients,who received the treatment with programmed death receptor 1(PD-1)inhibitors at Guang'anmen Hospital,China Academy of Chinese Medical Sciences from January 2020 to October 2024.Clinical data and TCM four-examination data were collected.After balancing the confounders via PSM(1∶1 matching)and with therapeutic efficacy as the dependent variable,multivariate logistic regression was performed to analyze the characteristics of TCM syndrome in the immunotherapy-response group and then a predictive model was constructed.Results(1)After matching with PSM,198 cases were included,99 cases in response group and 99 cases in non-response group.(2)Analysis of the distribution of TCM syndrome elements showed that the differences in the pathogenic syndrome elements of qi deficiency,qi stagnation,blood stasis,heat and phlegm between the two groups were statistically significant(P＜0.05 or P＜0.01),while there were no statistically significant differences in the disease-location syndrome elements of uterus,kidneys,lungs,spleen,liver,and heart,as well as in the pathogenic syndrome elements of blood deficiency,yin deficiency,yang deficiency,cold,and dampness(P＞0.05).The main pathogenic syndrome elements in the response group were qi deficiency,blood deficiency and heat,while those in the non-response group were qi stagnation,heat and phlegm.(3)The results of univariate regression analysis showed that targeted therapy(P=0.040),programmed cell death-ligand 1(PD-L1)expression level(P＜0.001),qi deficiency(P=0.009),blood deficiency(P＜0.001),yang deficiency(P＜0.001),yin deficiency(P＜0.001),qi stagnation(P=0.003),blood stasis(P＜0.001),cold(P＜0.001),cold(P＜0.001),heat(P＜0.001),phlegm(P＜0.001),and dampness(P＜0.001)were the factors associated with the efficacy of PD-1 inhibitors.(4)The results of multivariate logistic regression analysis showed that previous targeted therapy(OR=0.36,95%CI:0.16-0.83)and pathogenic syndrome elements of qi stagnation(OR=0.23,95%CI:0.10-0.49),phlegm(OR=0.28,95%CI:0.13-0.61)were the risk factors of associated with the efficacy of PD-1 inhibitors,while PD-L1 expression level(OR=15.27,95%CI:2.60-89.63),and pathogenic syndrome element qi deficiency(OR=2.90,95%CI:1.42-5.89)were the protective factors associated with the efficacy of PD-1 inhibitors in cervical cancer.(5)Receiver operating characteristic(ROC)curve analysis demonstrated that the area under the ROC curve(AUC)of the predictive model for evaluating PD-1 inhibitor efficacy in cervical cancer was 0.78(95%CI:0.71-0.84),indicating certain predictive value.Conclusion PD-L1 expression level and TCM pathogenic syndrome elements such as qi deficiency,qi stagnation,and phlegm are the independent factors influencing PD-1 inhibitor efficacy in cervical cancer,providing insights for optimizing integrated TCM-western medicine treatment strategies.

The aim of this updated guideline is to provide comprehensive recommendations for the management of gout in patients with common comorbidities, such as chronic kidney disease(CKD), cardiovascular disease(CVD), diabetes, osteoarthritis(OA), and gastrointestinal disorders. This guideline was developed by a multidisciplinary expert panel consisting of specialists in endocrinology, rheumatology, nephrology, cardiology, gastroenterology, and methodology. The development process adhered to standard methodologies, including PICO(population, intervention, comparator, and outcomes) question deconstruction, systematic literature review, the Grading of Recommendations Assessment, Development and Evaluation(GRADE) for evidence and recommendation evaluation, Delphi voting, and expert consensus. The guideline presents 26 evidence-based recommendations addressing 7 clinical questions for patients with hyperuricemia and gout in the context of comorbidities. Key recommendations include the maintenance of strict serum urate targets, particularly for patients with CKD stage≥3, chronic gouty arthritis, and OA, in order to prevent disease progression. In patients with CVD or diabetes, intra-articular triamcinolone is preferred over systemic glucocorticoids. Prioritized anti-inflammatory treatments for patients with CKD, gastrointestinal diseases and OA are recommended. The guideline also introduces emerging therapies, such as interleukin-1 inhibitors and selective urate transport inhibitors, as potential treatment options for refractory cases. The update offers a comprehensive, patient-centered approach to managing gout, particularly in individuals with associated comorbidities. Multidisciplinary collaboration and emerging new treatments and evidence ensure the optimization of the recommendations.

Objective:To investigate the relationship between Triglyceride Glucose-WHR index and retinal arteriosclerosis.Methods:Retrospective longitudinal cohort research method. Using data from the Tongren Health Care Study of Beijing Tongren Hospital from March 2014 to June 2020. The TyG-WHR index was calculated, the restricted cubic spine regression model was used to explore the dose-response relationship between TyG-WHR index and the risk of retinal arteriosclerosis. Cox proportional regression model was implemented to estimate the impact on the risk of retinal arteriosclerosis associated with the different TyG-WHR groups. Receiver operating characteristic were used to explore the value of triglyceride glucose-WHR index for the risk of retinal arteriosclerosis.Results:A total of 8 215 subjects were included, including 3 334 (40.58%) males, 4 881 (59.42%) females;7 689 cases had normal fundus, 296 cases had newly developed retinal arteriosclerosis, and 230 cases had retinal arteriosclerosis. The median age is 45 years old, and the average age is (47.63±13.89) years old. The cumulative incidence rate of new retinal arteriosclerosis was 3.71%(296/7 985), and the cumulative incidence rate of women (3.31%,158/4 767) was lower than that of men (4.29%, 138/3 218) ( χ2=5.105, P<0.001); The cumulative incidence rate of new retinal arteriosclerosis increased with age ( χ2=365.133, P<0.001); The TyG-WHR index was divided into four groups according to the interquartile range, and the Q2- Q4 group had an increased risk of developing new retinal arteriosclerosis compared to Q1 ( χ2=132.887, P<0.001).In the restricted cubic spine regression model, the results showed a non-linear dose-response relationship ( χ2=54.27, P<0.001) between baseline TyG-WHR index and the new-onset of retinal arteriosclerosis. By the multivariate Cox Regression models, three models were constructed in this study. TyG-WHR index was positively correlated with the risk of retinal arteriosclerosis: the HR (95% CI) of model 1-3 was 1.534,1.517 and 1.502.The AUC curve analysis verified that the prediction AUC of the TyG-WHR index for new-onset retinal arteriosclerosis was 0.755, the best prediction value was 7.343, the sensitivity was 90.2%, and the specificity was 75.60%. Conclusion:TyG-WHR index may be an independent risk factor for new-onset retinal arteriosclerosis.

Objective:To investigate the early right heart function management strategy and prognosis after left ventricular assist device(LVAD) implantation in patients with preoperative right ventricular dysfunction.Methods:A retrospective study was conducted. From March 2022 to April 2024, a total of 28 patients with end-stage heart failure underwent LVAD implantation at Nanjing First Hospital and were admitted to the intensive care unit(ICU) after surgery. Among them, patients with preoperative right ventricular dysfunction were enrolled. All patients were implanted with Corheart 6 implantable left ventricular assist device. The clinical data, occurrence of postoperative right heart failure and postoperative survival situations of enrolled patients were collected and analyzed.Results:A total of 12 patients were included in this study, including 11 males and 1 female, the mean age was(58.4±7.6) years old. Upon postoperative admission to ICU, the most commonly used positive inotropic agent was epinephrine(9 cases), followed by dobutamine(8 cases). By the second day after surgery, the most frequently utilized vasoactive medications were epinephrine and phosphodiesterase type Ⅲ inhibitors, both with 9 cases of usage. None of the enrolled patients utilized temporary mechanical circulatory assist devices. The LVAD pump speed of the patients enrolled in the study was set at approximately 2 700 revolutions per minute, and the pump flow was approximately 3 liters per minute. During the first two days after the operation, the fluid balance of the enrolled patients ranged from(-523.4±775.6)ml to(-1 248.0±1 023.9)ml. At 48 h following the operation, the mean pulmonary artery pressure(MPAP)[(26.2±4.8) mmHg vs.(32.1±6.5) mmHg(1 mmHg=0.133 kPa), P=0.042] and the pulmonary artery wedge pressure(PAWP)[(15.6±5.5)mmHg vs.(24.9±5.9) mmHg, P=0.003) ] of the enrolled patients were significantly decreased compared to preoperative levels, while the cardiac index(CI) was significantly improved[(2.7±0.2)L·min -1·m -2 vs.(2.1±0.5)L·min -1·m -2,P=0.024]. Echocardiography showed that the left atrial diameter(LAD)[(51.5±7.6)mm vs.(57.2±9.0)mm, P=0.005] and left ventricular end diastolic diameter(LVDd)[(73.5±11.5)mm vs.(78.3 ± 12.3)mm, P=0.012) ] were significantly reduced post LVAD implantation as compared to before LVAD implantation, while there was no significant difference in tricuspid annular plane systolic excusion(TAPSE). Postoperative total bilirubin(TBIL) decreased significantly compared to preoperative levels[(15.5±5.0)μmol/L vs.(27.5±17.0)μmol/L, P=0.038]. Three patients experienced right heart failure after the LVAD implantation, with an incidence rate of 25%. Nevertheless, the right heart failure was rectified during the ICU treatment period. The mean ICU treatment time for all enrolled patients was(8.6±2.9) days, the average postoperative hospital stay was(24.3±4.8) days. All enrolled patients survived at 3 months after LVAD implantation. Conclusion:Despite the presence of right ventricular dysfunction in patients before LVAD implantation, with strict fluid management, reasonable LVAD parameters, and appropriate vasoactive drugs, they are able to smoothly pass through the perioperative period, achieve the goals of left ventricular decompression, increase cardiac output, improve perfusion of the end organs, and obtain favorable short-term therapeutic effects.

OBJECTIVE: To investigate the effects of liriodendrin on the intestinal flora and the ferroptosis signaling pathway in renal tissue of rats with sepsis-induced acute kidney injury (AKI). METHODS: Thirty male Sprague-Dawley (SD) rats were randomly divided into sham operation group (Sham group), sepsis model induced by cecal ligation and puncture group (CLP group), and liriodendrin intervention group (CLP+LIR group), with 10 rats in each group. The CLP+LIR group was given 0.2 mL of 100 mg/kg liriodendrin by gavage 2 hours before modeling; Sham group and CLP group were given the same volume of normal saline by gavage. The samples were collected after anesthesia 24 hours after modeling. The pathological changes of renal tissue were observed by hematoxylin-eosin (HE) staining. The levels of inflammatory factors such as tumor necrosis factor-α (TNF-α), interleukins (IL-1β, IL-6) were detected by enzyme linked immunosorbent assay (ELISA). The levels of renal function indicators such as creatinine (Cr), and urea nitrogen (UREA) in peripheral blood, and the content of malondialdehyde (MDA) and Fe²⁺ in renal tissue were detected. Western blotting was used to detect the expressions of nuclear factor E2-related factor 2 (Nrf2), glutathione peroxidase 4 (GPX4) and heme oxygenase-1 (HO-1) in renal tissues. The changes of intestinal flora were detected by 16S rDNA high-throughput sequencing. RESULTS: Compared with the Sham group, the CLP group showed significantly enlarged glomeruli, noticeable renal interstitial edema, disorganized kidney tissue, and significantly increased pathological scores. The contents of TNF-α, IL-1β, IL-6, Cr, and UREA in peripheral blood and the levels of MDA and Fe²⁺ in renal tissue were significantly increased. The protein expressions of Nrf2, GPX4, and HO-1 in renal tissue were significantly down-regulated. The species richness of intestinal flora decreased significantly, and the relative abundances of pathogenic bacteria such as Morganella, Citrobacter, Proteus, Klebsiella, Shigella, Aggregatibacter, and Enterococcus increased significantly, while the relative abundances of beneficial bacteria such as Butyricimonas, Veillonella, Prevotella, Lactobacillus, Bifidobacterium, and Ruminococcus decreased significantly. Compared with the CLP group, CLP+LIR group could significantly reduce the pathological damage of renal tissue, the pathological score significantly decreased (1.80±0.84 vs. 4.20±1.30, P < 0.05), and improve the composition of intestinal flora, reduce the relative abundances of pathogenic bacteria such as Proteus, Klebsiella, Shigella, Aggregatibacter, and Enterococcus, and significantly increase the relative abundances of Lactobacillus, Bifidobacterium, and Ruminococcus, significantly reduce the contents of TNF-α, IL-1β, IL-6, Cr, and UREA in peripheral blood and the levels of MDA and Fe²⁺ in renal tissue [blood TNF-α (ng/L): 191.31±7.23 vs. 254.90±47.89, blood IL-1β (ng/L): 11.15±4.04 vs. 23.06±1.67, blood IL-6 (ng/L): 163.20±17.83 vs. 267.69±20.92, blood Cr (μmol/L): 24.14±4.25 vs. 41.17±5.43, blood UREA (mmol/L): 4.59±0.90 vs. 8.01±1.07, renal MDA (μmol/g): 9.67±0.46 vs. 16.05±0.88, renal Fe²⁺ (mg/g): 0.71±0.07 vs. 0.93±0.04, all P < 0.05], and increase the protein expressions of Nrf2, GPX4, and HO-1 (Nrf2/GAPDH: 1.21±0.01 vs. 0.39±0.01, GPX4/GAPDH: 0.74±0.04 vs. 0.48±0.04, HO-1/GAPDH: 0.91±0.01 vs. 0.41±0.02, all P < 0.05). CONCLUSIONS Liriodendrin has an obvious protective effect on sepsis-induced AKI. The mechanism may involve regulating the intestinal flora, increasing the activation of the Nrf2/HO-1/GPX4 signaling pathway in renal tissue, and reducing ferroptosis.
Animals ; Acute Kidney Injury/microbiology* ; Rats, Sprague-Dawley ; Sepsis/complications* ; Male ; Ferroptosis/drug effects* ; Gastrointestinal Microbiome/drug effects* ; Rats ; Signal Transduction ; Kidney/metabolism* ; Tumor Necrosis Factor-alpha/metabolism*

AIM To explore the effects of Hofmeister series ions on encapsulation efficiencies of cinnamaldehyde,paeonol,and ligustilide in inclusion complex of volatile oils from Wenjing Decoction.METHODS The volatile oils were extracted,after which the β-cyclodextrin inclusion complex was prepared,the thermal stability was evaluated,and encapsulation efficiencies and inclusion complex constants of various volatile components in Na2SO4,NaH2PO4,NaCl,NaI,NaSCN solutions were determined.RESULTS The β-cyclodextrin inclusion complex demonstrated good thermal stability within 10 d.After the addtion of Hofmeister series ions,various volatile components displayed increased encapsulation efficiencies and inclusion complex constants,and concentration-dependent manner was observable in the latter.CONCLUSION Hofmeister series ions can affect the binding affinities of volatile components and β-cyclodextrin in volatile oils from Wenjing Decoction,thus regulate their encapsulation efficiencies.