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.

Objective:To explore the intimal injury of two kinds of hemostatic clips under different clamping forces, and to optimize and verify the calculation formula of minimum occlusion force (MOF), so as to provide theoretical basis for selecting appropriate hemostatic clips to reduce vascular injury.Methods:A total of 96 male SD rats with body weight ranging from 280 to 300 g (Animal Experimental Center of Shanxi Medical University) were randomly assigned to metal hemostatic clip group ( n=48) and disposable hemostatic clip group ( n=48) by random number table method. Each group was further divided into four subgroups with clamping forces of 0.3, 0.6, 0.9 and 1.2 N for abdominal aortic injury experiments. The damage to the vascular intima was observed under a scanning electron microscope. A vascular closure model was established for mathematical analysis to derive the theoretical calculation formula of the arterial blood management factor (MOF). According to blood pressure (BP), blood vessel diameter (D) and hemostatic clamp width (W), the average values of theoretical and actual MOF data were analyzed by paired t test to verify the accuracy of the formula. From January 2021 to December 2022, six patients (with 12 branch arteries) who presented with oral and maxillofacial malignancies at the Department of Oral and Maxillofacial Surgery, Shanxi Medical University School and Hospital of Stomatology, were included to validate the accuracy of the MOF formula. Results:Under electron microscopy, when the clamping force was 0.3 N, the one-time hemostatic clip caused very little damage to the vascular intima (grade 1 injury), with only a few folds being flattened. When the clamping force was 0.6 N, both types of hemostatic clips caused partial peeling of the intima surface (grade 2-3 injury). However, when the clamping force was adjusted to 0.9 and 1.2 N, the damage caused by both types of hemostatic clips was more severe (grade 3-4 injury), with large areas of intima peeling or even disappearance. In some specimens of the metal hemostatic clip group, the damage even reached the muscular layer. Vascular closure model analysis showed that MOF=2×(1/2×π×D×W×BP), the mean diameter of abdominal aorta of 24 SD rats was (1.41±0.07) mm, the blood pressure was (83.29±11.56) mmHg (1 mmHg=0.133 kPa). The theoretical MOF value was (0.096±0.015) N, the actual clamping force (ACF) was (0.095±0.012) N, there was no statistical significance between the two groups ( t=-0.35, P=0.725). In clinical application, the MOF calculation formula was used to select the appropriate hemostatic clip for 12 arteries, successfully blocking the blood flow, verifying the accuracy of the formula. Conclusions:Hemostatic clips can cause damage to the inner membrane of blood vessels, and the greater the clamping force, the more severe the damage. Disposable hemostatic clips have certain advantages in avoiding excessive damage to the inner membrane of blood vessels. The theoretical MOF calculation formula has a certain degree of reliability and can be used as a reference to select the appropriate hemostatic clip with low damage.

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 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 explore the intimal injury of two kinds of hemostatic clips under different clamping forces, and to optimize and verify the calculation formula of minimum occlusion force (MOF), so as to provide theoretical basis for selecting appropriate hemostatic clips to reduce vascular injury.Methods:A total of 96 male SD rats with body weight ranging from 280 to 300 g (Animal Experimental Center of Shanxi Medical University) were randomly assigned to metal hemostatic clip group ( n=48) and disposable hemostatic clip group ( n=48) by random number table method. Each group was further divided into four subgroups with clamping forces of 0.3, 0.6, 0.9 and 1.2 N for abdominal aortic injury experiments. The damage to the vascular intima was observed under a scanning electron microscope. A vascular closure model was established for mathematical analysis to derive the theoretical calculation formula of the arterial blood management factor (MOF). According to blood pressure (BP), blood vessel diameter (D) and hemostatic clamp width (W), the average values of theoretical and actual MOF data were analyzed by paired t test to verify the accuracy of the formula. From January 2021 to December 2022, six patients (with 12 branch arteries) who presented with oral and maxillofacial malignancies at the Department of Oral and Maxillofacial Surgery, Shanxi Medical University School and Hospital of Stomatology, were included to validate the accuracy of the MOF formula. Results:Under electron microscopy, when the clamping force was 0.3 N, the one-time hemostatic clip caused very little damage to the vascular intima (grade 1 injury), with only a few folds being flattened. When the clamping force was 0.6 N, both types of hemostatic clips caused partial peeling of the intima surface (grade 2-3 injury). However, when the clamping force was adjusted to 0.9 and 1.2 N, the damage caused by both types of hemostatic clips was more severe (grade 3-4 injury), with large areas of intima peeling or even disappearance. In some specimens of the metal hemostatic clip group, the damage even reached the muscular layer. Vascular closure model analysis showed that MOF=2×(1/2×π×D×W×BP), the mean diameter of abdominal aorta of 24 SD rats was (1.41±0.07) mm, the blood pressure was (83.29±11.56) mmHg (1 mmHg=0.133 kPa). The theoretical MOF value was (0.096±0.015) N, the actual clamping force (ACF) was (0.095±0.012) N, there was no statistical significance between the two groups ( t=-0.35, P=0.725). In clinical application, the MOF calculation formula was used to select the appropriate hemostatic clip for 12 arteries, successfully blocking the blood flow, verifying the accuracy of the formula. Conclusions:Hemostatic clips can cause damage to the inner membrane of blood vessels, and the greater the clamping force, the more severe the damage. Disposable hemostatic clips have certain advantages in avoiding excessive damage to the inner membrane of blood vessels. The theoretical MOF calculation formula has a certain degree of reliability and can be used as a reference to select the appropriate hemostatic clip with low damage.

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.

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.

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 construct a prediction model for post-neoadjuvant therapy recurrent laryngeal nerve lymph node(RLN LN)status via clinical and CT image data in esophageal cancer patients pre-neoadjuvant therapy.Methods A retrospective analysis was conducted on 403 patients with locally advanced esophageal cancer who received neoadjuvant therapy and radical resection for esophageal cancer.All patients were divided into a training cohort(n=270)and a validation cohort(n=133)randomly according to a 2:1 ratio.Clinical and imaging features associated with positive RLN LN pathology were selected by univariate analysis.Multivariate logistic stepwise regression model was used to construct the prediction model.The prediction ability of the model was evaluated by receiver operating characteristic(ROC)curve.Results The basic model included neoadjuvant therapy and RLN LN short diameter,with an area under the curve(AUC)of 0.7(training cohort)and 0.65(validation cohort).The final prediction model included neoadjuvant therapy,human albumin,platelet count,largest lymph node enhancement characteristics,whether the largest lymph node was in the recurrent laryngeal region,and RLN LN short diameter,with AUC of 0.83[95％confidence interval(CI)0.768-0.899]and 0.76(95％CI 0.645-0.887)for the training and validation cohorts,respectively.Conclusion The model based on clinical data and imaging features pre-neoadjuvant therapy for esophageal cancer can assist in clinically predicting the post-neoadjuvant therapy RLN LN status.

Objective:To investigate the predictive value of preoperative γ-glutamyl transferase/lymphocyte count ratio (GLR) levels for postoperative tumor recurrence in liver transplant recipients with liver cancer.Methods:The clinical data of 158 recipients who were diagnosed with hepatocellular carcinoma (hereinafter referred to as liver cancer) and received liver transplantation at the No. 900 Hospital of the Joint Logistics Support Force of the Chinese People's Liberation Army from January 2008 to October 2022 were retrospectively analyzed. X-tile software, the Kaplan-Meier method, univariate and multivariate Cox regression, and other statistical methods were performed. The predictive value of preoperative GLR levels for postoperative tumor recurrence in liver transplant recipients with liver cancer and the risk factors for tumor recurrence in liver cancer patients post-liver transplantation were analyzed.Results:The X-tile software analysis confirmed that 96.8 was the optimal cutoff value for the preoperative GLR level to predict recurrence. The grouping threshold for survival analysis using the GLR cutoff value was 96.8. The tumor recurrence rates at 1, 3, and 5 years after surgery in the low-level GLR group (90 cases) and the high-level GLR group were 19.3% vs. 44.2%, 31.8% vs. 60.0%, and 34.1% vs. 62.9% (68 cases), respectively, and the differences were statistically significant between the two groups ( P<0.05). The Kaplan-Meier survival curve analysis results showed that the overall postoperative survival rate and recurrence-free survival rate were significantly lower in the high-level GLR group than the low-level GLR group ( P<0.05). The univariate Cox analysis result showed that there were statistically significant differences in preoperative aspartate aminotransferase, alpha fetoprotein, surgery time, maximum diameter of a solitary tumor, presence or absence of microvascular invasion, presence or absence of portal vein tumor thrombus, and preoperative GLR levels between the two groups ( P<0.05). Multivariate Cox analysis results showed that preoperative alpha-fetoprotein ≥400 ng/ml, GLR≥96.8, and the maximum diameter of a solitary tumor ≥5.0 cm were independent risk factors for postoperative tumor recurrence in liver transplant recipients with liver cancer ( P<0.05). Conclusion:GLR levels have a certain predictive value for postoperative tumor recurrence in liver transplant recipients with liver cancer. Furthermore, the postoperative tumor recurrence rate is relatively high when the preoperative GLR level in liver transplant recipients with liver cancer is ≥96.8.