Objective To investigate the potential mechanism of nicotinamide combined with amphotericin B against Candida albicans based on metabolomics. Methods The intracellular metabolites of C. albicans intervened by different drugs including NAM, AmB, and their combination with a proper concentration were analyzed by gas chromatography-mass spectrometry. The differential metabolites were screened by multivariate statistical analysis and identified by searching the NIST database. Results Compared with the control group, the NAM intervention group was hardly separated from it, while the AmB group and NAM+AmB group showed a clear trend of separation. Under the intervention of AmB, 23 metabolites significantly changed compared with the control group, and 28 metabolites remarkably changed after NAM+AmB intervention, including amino acids, organic acids, sugars and other components. Conclusion NAM, as an endogenous metabolite of C. albicans, combined with AmB could enhance the effects of AmB in the original metabolic pathway and changed it to a certain extent. It was speculated that AmB combined with NAM may pose more antifungal effect on Candida albicans by regulating the tricarboxylic acid cycle，interfering with amino acid metabolism and influencing polyamine synthesis.

AIM: To investigate the current incidence of retinopathy of prematurity(ROP)in Sichuan Province and analyze its risk factors, providing a scientific basis for establishing and improving the regional ROP screening and prevention system.METHODS: A retrospective study was conducted on premature infants who underwent fundus screening at the Departments of Ophthalmology and Neonatology of Sichuan Provincial Maternity and Child Health Care Hospital from January 20, 2017 to February 10, 2025. The incidence of ROP was calculated. The patients were divided into ROP group and non-ROP group according to whether ROP occurred, and the clinical characteristics of the two groups were compared. Multivariate Logistic regression was used to analyze risk factors for ROP.RESULTS:This study included a total of 861 premature infants, with 445 males(51.7%)and 416 females(48.3%).ROP occurred in 166 cases, with an incidence rate of 19.3%, and the non-ROP group consisted of 695 cases. The mean gestational age of the ROP and non-ROP groups was 30.24±2.20 and 33.06±1.90 wk(P<0.01), while the mean birth weight was 1438.94±389.66 and 1977.32±438.68 g(P<0.01). By comparing the clinical data of the two groups of preterm infants, the following factors were found to be associated with the occurrence of ROP: younger gestational age, low birth weight, history of oxygen therapy, respiratory distress syndrome, intracranial hemorrhage, neonatal anemia, bronchopulmonary dysplasia, patent ductus arteriosus, and sepsis(all P<0.01). Multivariate Logistic regression analysis revealed that gestational age(OR=0.685,95%CI:0.592-0.792,P<0.01), birth weight(OR=0.999,95%CI:0.998-0.999,P<0.01), and respiratory distress syndrome(OR=2.312,95%CI:1.313-4.070,P<0.01)were risk factors for ROP. Gestational age had the greatest impact.The younger the gestational age at birth, the higher the risk of ROP.CONCLUSION:The incidence of ROP in Sichuan Province is relatively high compared to multicenter results from China. Significant risk factors include younger gestational age, low birth weight, and respiratory distress syndrome. Screening criteria should be formulated based on the local incidence of ROP, and a screening, prevention, and treatment system for ROP should be established and improved.

Objective:To evaluate the differences in total effectiveness, Visual Analogue Scale (VAS) scores, and Cox Menstrual Symptom Scale (CMSS) scores among four non-invasive Traditional Chinese Medicine (TCM) techniques: moxibustion, massage therapy, acupoint application, and auricular acupressure, for the care of primary dysmenorrhea (PD) using network Meta-analysis, providing evidence-based guidance for clinical decision-making.Methods:Randomized controlled trials (RCTs) involving the four non-invasive TCM techniques for PD care were retrieved from databases including China National Knowledge Infrastructure, VIP, Wanfang, SinoMed, PubMed, Embase, Web of Science, and Cochrane Library up to November 30, 2023. Network Meta-analysis was conducted using RevMan 5.4 and Stata 17.0.Results:A total of 83 studies involving 8 370 PD patients were included. The network Meta-analysis showed that all four TCM techniques were superior to control measures in terms of total effectiveness and reducing VAS scores. Moxibustion, acupoint application, and auricular acupressure were also superior in reducing CMSS scores. Ranking of the effects of different interventions: total effectiveness: auricular acupressure > moxibustion > acupoint application > massage therapy > acupuncture > Chinese patent medicine > Western medicine > blank control > placebo treatment; VAS scores: moxibustion > auricular acupressure > acupoint application > acupuncture > placebo treatment > massage therapy > Western medicine > Chinese patent medicine > blank control; CMSS scores: auricular acupressure > moxibustion > acupuncture > placebo treatment > acupoint application > Western medicine > blank control.Conclusions:The four non-invasive TCM techniques have significant advantages in PD care, with auricular acupressure and moxibustion being the preferred choices for clinical care.

Two novel diketopiperazines (1 and 5), along with ten known compounds (2-4, 6-12) demonstrating significant skin inflammation inhibition, were isolated from a marine-derived fungus identified as Aspergillus sp. FAZW0001. The structural elucidation and configurational reassessments of compounds 1-5 were established through comprehensive spectral analyses, with their absolute configurations determined via single crystal X-ray diffraction using Cu Kα radiation, Marfey's method, and comparison between experimental and calculated electronic circular dichroism (ECD) spectra. Compounds 1, 2, and 8 exhibited significant anti-inflammatory activities in Propionibacterium acnes (P. acnes)-induced human monocyte cell lines. Compound 8 demonstrated the ability to down-regulate interleukin-1β (IL-1β) expression by inhibiting Toll-like receptor 2 (TLR2) expression and modulating the activation of myeloid differentiation factor 88 (MyD88), mitogen-activated protein kinase (MAPK), and nuclear factor κB (NF-κB) signaling pathways, thus reducing the cellular inflammatory response induced by P. acnes. Additionally, compound 8 showed the capacity to suppress mitochondrial reactive oxygen species (ROS) production and nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) inflammasome activation, thereby reducing IL-1β maturation and secretion. A three-dimensional quantitative structure-activity relationships (3D-QSAR) model was applied to compounds 5-12 to analyze their anti-inflammatory structure-activity relationships.
Humans ; Aspergillus/chemistry* ; Diketopiperazines/isolation & purification* ; Anti-Inflammatory Agents/isolation & purification* ; Interleukin-1beta/genetics* ; Toll-Like Receptor 2/immunology* ; Propionibacterium acnes/drug effects* ; NF-kappa B/genetics* ; Molecular Structure ; Myeloid Differentiation Factor 88/immunology* ; Monocytes/immunology* ; NLR Family, Pyrin Domain-Containing 3 Protein/genetics* ; Cell Line

Objective:To study the impact of early blood concentrations of tacrolimus on the survival of patients after liver transplantation.Methods:Clinical data of 159 patients with liver diseases undergoing classic orthotopic liver transplantation at the Department of Hepatobiliary Surgery, the 900th Hospital of the Joint Logistics Support Force between January 2010 and December 2019 were retrospectively analyzed, including 123 males and 36 females, aged (48.0±12.2) years. According to survival status, patients were divided into the surviving group ( n=108) and death group ( n=51). Inverse probability of treatment weighting (IPTW) was applied to adjust for confounding factors by weighting covariates between the two groups. Univariate and multivariate Cox regression analysis were used to examine the relationship between early tacrolimus concentrations and mortality, and restrict cubic spline (RCS) curves were employed to assess the nonlinear relationship further. Results:After IPTW weighting, multivariate Cox regression analysis indicated that early tacrolimus concentration ( HR=2.479, 95% CI: 1.354-4.537, P<0.001) and preoperative international normalized ratio ( HR=0.358, 95% CI: 0.162-0.792, P=0.011) levels were risk factors for post-transplant survival. The RCS curve revealed that the optimal thresholds for early tacrolimus concentration were 6.30 ng/ml and 8.28 ng/ml ( P<0.001). Patients were therefore divided into the optimal concentration group ( n=60) and the non-optimal concentration group ( n=99). After IPTW weighting, the optimal concentration group comprised 102 cases, and the non-optimal concentration group included 212 cases. The 1-year, 3-year and 5-year survival rates in the optimal concentration group and the non-optimal concentration group were 97.06%, 81.37% and 75.49%, and 86.32%, 64.62% and 50.94%, respecitvely ( χ2=8.37, P<0.001). Conclusion:Early tacrolimus concentration is an independent risk factor for post-transplant survival. A tacrolimus concentration >8.28 ng/ml or <6.30 ng/ml is associated with a relatively higher mortality rate.

Objective:To analyze the effects of hemoglobin, albumin, lymphocyte and platelet count (HALP) scores on the survival of gallbladder cancer patients after radical surgery, and to construct a prognostic prediction model and evaluate based on HALP scores.Methods:The clinical data of 95 patients with gallbladder cancer who underwent surgical treatment in Fuzong Clinical Medical College of Fujian Medical University (the 900th Hospital) from January 2010 to December 2022 were retrospectively analyzed, including 40 males and 55 females, with the age of (63.3±12.2) years. All patients were divided into a low HALP group (HALP score ≤35.4, n=45) and a high HALP group (HALP score >35.4, n=50) based on the optimal cut-off value of 35.4 for predicting postoperative survival as determined by the receiver operating characteristic (ROC) curve. Survival curves were plotted by the Kaplan-Meier method, and survival comparisons were performed using the log-rank test. Univariate and multivariate Cox regression were used to analyze the effect of HALP score on survival after radical surgery in patients with gallbladder cancer. Based on the multifactorial results, nomogram was constructed to predict the survival of gallbladder cancer patients after radical surgery, and ROC curves, consistency indexes were evaluated in the model. Results:A total of 95 patients were followed up for 1-150 months, with a median of 13 months. The 1-, 3-, and 5-year postoperative cumulative survival rates of patients in the low HALP group were 56.2%, 31.2%, and 11.1%, respectively, which were lower than those of the high HALP group, which were 82.9%, 59.6%, and 40.7%, and the difference was statistically significant ( χ2=12.50, P<0.001). Based on multifactorial Cox regression analysis, preoperative total bilirubin ≥23 μmol/L, with lymph node metastasis, tumor TNM stage Ⅲ-Ⅳ, and postoperative incision infection were the risk factors for survival after radical surgery in patients with gallbladder cancer, and a HALP score of >35.4 and Child-Pugh A were protective factors (all P<0.05). Based on the results of multivariate Cox regression analysis to construct a nomogram for predicting overall survival after radical surgery in patients with gallbladder cancer, the consistency index between the prediction of the nomogram and the actual situation was 0.801 (95% CI: 0.752-0.850), and the area under the ROC curve for predicting overall survival was 0.812 (95% CI: 0.704-0.902). Conclusion:The preoperative high HALP score (HALP > 35.4) is a protective factor for survival after radical surgery in gallbladder cancer patients, and the nomogram constructed based on the HALP score for survival prediction after radical surgery for gallbladder cancer has high accuracy and can be used for the assessment of postoperative survival.

Objective:To elucidate the prognostic differences and risk factors associated with different patterns of recurrence and metastasis following pancreatic cancer (PC) resection.Methods:This is a retrospective case series study. Clinicopathological data and follow-up information were retrospectively collected from 210 patients who underwent surgery for PC at the Department of Hepatobiliary and Pancreatic Surgery, Peking University First Hospital, between January 2014 and December 2023. There were 114 males and 96 females; the age was (64.5±10.3) years (range: 29 to 89 years). Survival functions based on different times to recurrence and metastasis and different patterns of recurrence and metastasis were estimated using the Kaplan-Meier method, and survival differences among groups were compared using the Log-rank test. Identifying the optimal cutoff for time to postoperative recurrence/metastasis predicting overall survival (OS) in pancreatic cancer patients via the minimum p-value approach. Univariate and multivariate Cox regression analyses were performed to identify independent risk factors affecting OS following pancreatectomy.Results:A total of 210 patients met the inclusion and exclusion criteria. Among them, 71 patients remained free of recurrence and metastasis, while 139 developed recurrence and metastasis. The patterns included local recurrence ( n=34), liver metastasis ( n=39), lung metastasis ( n=11), peritoneal metastasis ( n=13), multiple sites metastasis ( n=38), bone metastasis ( n=3), and kidney metastasis ( n=1). OS was significantly shorter in the group with postoperative recurrence and metastasis compared to the group without recurrence/metastasis (23.07 months vs.not reached, P<0.01). The optimal cut-off time distinguishing early from late recurrence and metastasis was 13 months. There was a significant difference in post-recurrence survival between patients with early and late recurrence and metastasis (16.03 months vs. 52.40 months, P=0.009). The Kaplan-Meier survival curve showed that different postoperative recurrence and metastasis patterns had different impacts on OS, with lung metastasis showing the best prognosis compared to local recurrence, liver metastasis, peritoneal metastasis, and multiple sites metastasis ( P<0.01). Multivariate Cox analysis revealed that Eastern Cooperative Oncology Group (ECOG) score 1, postoperative carcinoembryonic antigen (CEA) ≥15 μg/L, poor tumor differentiation, postoperative local recurrence, liver metastasis, peritoneal metastasis, and multiple sites metastases are independent risk factors for postoperative recurrence and metastasis (all P<0.05). Conclusions:Considerable prognostic heterogeneity exists in postoperative PC patients depending on the site and pattern of recurrence or metastasis. Specifically, lung metastasis portends a significantly more favorable prognosis than liver metastasis, peritoneal metastasis, local recurrence, or multiple sites metastases. ECOG score 1, postoperative CEA≥15 μg/L, poor tumor differentiation, postoperative local recurrence, liver metastasis, peritoneal metastasis, and multiple sites metastases are independent risk factors for OS in postoperative PC patients.

Objective:To investigate the value of tumor and adipose tissue metabolic parameters from baseline 18F-FDG PET/CT in predicting the efficacy and prognosis of immunotherapy in patients with advanced nasopharyngeal carcinoma (NPC). Methods:From February 2019 to February 2022, 112 patients (91 males, 21 females, age 21-73 years) with advanced NPC who were treated with programmed death-1 (PD-1) inhibitors at Sun Yat-Sen University Cancer Center were retrospectively included. All patients underwent baseline PET/CT examination. Tumor and adipose tissue metabolic parameters were measured and calculated. Patients were divided into clinical benefit and non-clinical benefit groups, and Mann-Whitney U test or χ2 test was used to assess the differences between groups. Prognostic analysis of progression-free survival (PFS) was performed using multivariate Cox proportional hazards regression model and a prognostic stratification system was constructed. Results:Of the 112 patients, 85 were in the clinical benefit group and 27 were in the non-clinical benefit group. In non-clinical benefit group and clinical benefit group, the metabolic tumor volume (MTV) of primary tumor (PT-MTV) were 47.7(7.7, 81.2) and 14.0(5.7, 27.1)cm 3, total lesion glycolysis (TLG) of primary tumor (PT-TLG) were 228.9(27.4, 492.8) and 72.7(20.4, 165.5)g, whole-body MTV (WB-MTV) were 94.2(45.9, 215.4) and 61.3(31.6, 104.3)cm 3, whole-body TLG (WB-TLG) were 605.5(214.1, 1 402.5) and 319.2(172.4, 632.8)g, SUV max of visceral adipose tissue (SUV max-VAT) were 0.77(0.55, 0.91) and 0.62(0.48, 0.76), respectively ( Z values: from -2.72 to -1.96, all P<0.05). The proportion of patients with lung metastasis in non-clinical benefit group was higher than that in clinical benefit group (44.4%(12/27) vs 23.5%(20/85); χ2=4.39, P=0.036). PT-MTV (hazard ratio ( HR)=2.807, 95% CI: 1.540-5.118, P=0.001) and the presence of lung metastases ( HR=1.691, 95% CI: 1.012-2.823, P=0.045) were independent predictive factors for PFS in multivariate analysis. The prognostic prediction model based on the two predictive factors was able to significantly differentiate the prognosis in patients. Conclusions:Baseline tumor metabolic parameters and SUV max-VAT are associated with the efficacy of immunotherapy in patients with advanced NPC. PT-MTV and lung metastasis can independently predict PFS. The constructed prediction model can stratify patients′ prognosis.

Objective:To investigate the clinical-epidemiological characteristics of connective tissue diseases (CTD) complicated with pulmonary hypertension in Shanxi province from 2018 to 2021.Methods:This was a cross-sectional study. Data of CTD patients with pulmonary hypertension from 2018 to 2021 were collected from the Shanxi Provincial Health Statistics Direct Reporting System based on inpatient medical records. The demographic and clinical data of patients with different CTD types were analyzed.Results:A total of 1 697 CTD patients with pulmonary hypertension were included, among whom there were 451 cases (26.58%) of Sj?gren′s syndrome, 392 cases (23.10%) of systemic lupus erythematosus, 289 cases(17.03%) of systemic sclerosis, 109 cases (6.42%) of mixed CTD, 69 cases (4.07%) of Takayasu arteritis, and 387 cases (22.80%) of other CTD. The majority of patients were female (1 410 (83.09%)), and 783 cases (46.14%) were aged between 41 and 65 years, and 6 cases (0.35%) were performed right heart catheterization. The prevalence of CTD with pulmonary hypertension increased from 0.06/10 4 in 2018 to 0.20/10 4 in 2021. There were significant differences in the severity of pulmonary hypertension, New York Heart Association (NYHA) functional class, length of hospital stay, medical costs, and clinical outcomes among patients with different CTD subtypes (all P<0.001). Patients with systemic sclerosis had the highest proportion of NYHA functional class Ⅲ/Ⅳ(65.1%(188/289)), the longest length of hospital stays (13 (9, 18) days), the highest average medical costs (13 622.67 (8 636.38, 20 597.75) ￥(RMB)), and the lowest rate of improvement and discharge (51.90%(150/289)). Conclusions:Between 2018 and 2021, Shanxi province, where CTD is more common in Sj?gren′s syndrome, has a high proportion of women, a high proportion of people aged 41-65 years, and a low prevalence of right ventricular catheterization in patients with CTD complicated with pulmonary hypertension. The prevalence of CTD complicated with pulmonary hypertension shows a rising trend in Shanxi province from 2018 to 2021, while patients with systemic sclerosis exhibit the most severe cardiac impairment and poorer clinical outcomes compared to other subtypes.

Objective:To investigate the relationship between serum myosin-like BCL2 interacting protein (Beclin-1), tissue non-specific alkaline phosphatase (TNAP) and arrhythmia in patients with hypertension and chronic heart failure (CHF).Methods:A total of 121 patients with hypertension and CHF who experienced arrhythmia and 121 patients with hypertension and CHF who did not experience arrhythmia and were admitted to Xi'an Traditional Chinese Medicine Brain Disease Hospital from April 2022 to April 2024 were included as the study subjects, and were assigned into the occurrence group and the non occurrence group, respectively. Enzyme-linked immunosorbent assay (ELISA) method was applied to detect the expression levels of Beclin-1 and TNAP in the serum of patients with hypertension and CHF. Pearson method was applied to analyze the correlation between Beclin-1, TNAP levels and mean heart rate, New York Heart Association functional class (NYHA), left ventricular ejection fraction (LVEF), dynamic stiffness index (AASI), and N-terminal pro-brain natriuretic peptide (NT-proBNP) in patients with hypertension complicated with CHF arrhythmia. Multivariate logistic regression was applied to analyze the influencing factors of arrhythmia in patients with hypertension and CHF. Receiver operating characteristic (ROC) curve was applied to evaluate the diagnostic value of serum Beclin-1 and TNAP levels for arrhythmia in patients with hypertension and CHF.Results:The expression level of Beclin-1 in the serum of the occurrence group was lower than that of the non-occurrence group: (4.18 ± 1.12) μg/L vs. (5.26 ± 0.69) μg/L, while the TNAP level was higher than that of the non-occurrence group: (6.31 ± 1.32) μg/L vs. (5.27 ± 1.24) μg/L, and the differences were statistically significant ( P<0.05). In patients with hypertension combined with CHF and arrhythmia, Beclin-1 was negatively correlated with average heart rate, NYHA classification, AASI and NT-proBNP, and positively correlated with LVEF ( P<0.05), while TNAP was positively correlated with average heart rate, NYHA classification, AASI and NT-proBNP, and negatively correlated with LVEF ( P<0.05). Mean heart rate, NYHA classification, AASI, NT-proBNP and TNAP were risk factors for arrhythmia in patients with hypertension and CHF, while LVEF and Beclin-1 were protective factors for arrhythmia in patients with hypertension and CHF ( P<0.05). The AUC of Beclin-1 and TNAP in diagnosing arrhythmia in patients with hypertension and CHF was 0.813 and 0.818, respectively. When the AUC of their combined diagnosis increased to 0.904, the AUC of their combined diagnosis for arrhythmia in patients with hypertension and CHF was better than that of Beclin-1 ( Z = 2.583, P<0.05) and TNAP ( Z = 2.559, P<0.05). Conclusions:Beclin-1 is downregulated and TNAP is upregulated in the serum of patients with hypertension complicated with CHF and arrhythmia. The combination of the two has a high value in diagnosing arrhythmia in patients with hypertension and CHF.