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.

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.

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 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 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 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 investigate clinical curative effect of multiple composite tissues replantation with microsurgical technique in single hand.Methods:From May 2008 to December 2021, the clinical data of patients who underwent multiple composite tissue replantation in single hand in Chongming Hospital Affiliated to Shanghai University of Medicine & Health Sciences and Taizhou Hospital of Zhejiang Province, Wenzhou Medical University, were retrospectively analyzed. According to the severed site, anatomical level, the injury cause, the severity of injury, the size of severed tissue, and replantation conditions (such as blood vessels for anastomosis), the severed tissue was evaluated and carried out modified classification (type Ⅰ-Ⅳ) before the operation, and the surgical plan was designed. The severed composite tissue was debrided in emergency, the severed bone and muscle tissue were fixed, and the arteries, veins and nerves were anastomosed by microsurgical technique under a high-power microscope. The ratio of arteries to veins was 1∶1-1∶2. If enough arteries and veins could not be found, arteriovenous shunt could be used to form arterial venous flap or venous arterialized flap, or form artery flap by just artery anastomosis, or form venous flap by just vein anastomosis. Then skin tissue was sutured after recanalization. After the operation, the patients received specialized treatment and guided rehabilitation exercise. The wound healing of hand, skin color, skin quality, swelling degree, sensation, pain degree of joint, and activity function were followed up after the operation. At the last follow-up, the patient’s self-evaluation of the treatment effect was divided into three levels: satisfactory, average, and unsatisfactory. One chief physician and one doctor-in-charge were responsible for the comprehensive evaluation of curative effect, according to the assessment standard for upper limb function issued by Chinese Medical Association of Hand Surgery. 80-100 points were excellent, 60-79 points were good, 40-59 points were fair, and <40 points were poor.Results:A total of 94 severed composite tissues in 35 patients, including of 20 male patients and 15 female patients were enrolled. The average age was 36.4 years (range, 16-65 years). Fifty severed tissues in 18 cases were classified into type Ⅰ, 40 severed tissues in 15 cases type Ⅱ, 4 severed tissues in 2 cases type Ⅲ. Among the 35 cases, 1 case of thumb pulp severed tissue was necrotic at the edge (0.3 cm×0.5 cm) due to local contusion, 1 case of index finger lateral severed tissue was necrotic at the edge (0.3 cm×0.8 cm) due to local avulsion injury, and healed after dressing change, and the other replanted composite tissue survived. The patients were followed up for 3 to 65 months (average, 18.5 months). The wounds were completely healed, and the color, elasticity, and quality of the replanted tissue was close to the surrounding normal skin. There was no obvious swelling or atrophy deformity of the hands. According to the patients’ self-assessment, 31 cases were satisfied and 4 cases were average. Comprehensive evaluation of hand function and appearance: excellent in 23 cases, good in 9 cases, fair in 3 cases, excellent and good rate was about 91.4% (32/35).Conclusion:Though multiple composite tissues replantation with microsurgical technique in single hand is difficult, and vascular anastomosis technical requirement is high, once surgery succeeds, the function and appearance can get good recovery, and patient satisfaction is also relatively high.

Objective:To investigate clinical curative effect of multiple composite tissues replantation with microsurgical technique in single hand.Methods:From May 2008 to December 2021, the clinical data of patients who underwent multiple composite tissue replantation in single hand in Chongming Hospital Affiliated to Shanghai University of Medicine & Health Sciences and Taizhou Hospital of Zhejiang Province, Wenzhou Medical University, were retrospectively analyzed. According to the severed site, anatomical level, the injury cause, the severity of injury, the size of severed tissue, and replantation conditions (such as blood vessels for anastomosis), the severed tissue was evaluated and carried out modified classification (type Ⅰ-Ⅳ) before the operation, and the surgical plan was designed. The severed composite tissue was debrided in emergency, the severed bone and muscle tissue were fixed, and the arteries, veins and nerves were anastomosed by microsurgical technique under a high-power microscope. The ratio of arteries to veins was 1∶1-1∶2. If enough arteries and veins could not be found, arteriovenous shunt could be used to form arterial venous flap or venous arterialized flap, or form artery flap by just artery anastomosis, or form venous flap by just vein anastomosis. Then skin tissue was sutured after recanalization. After the operation, the patients received specialized treatment and guided rehabilitation exercise. The wound healing of hand, skin color, skin quality, swelling degree, sensation, pain degree of joint, and activity function were followed up after the operation. At the last follow-up, the patient’s self-evaluation of the treatment effect was divided into three levels: satisfactory, average, and unsatisfactory. One chief physician and one doctor-in-charge were responsible for the comprehensive evaluation of curative effect, according to the assessment standard for upper limb function issued by Chinese Medical Association of Hand Surgery. 80-100 points were excellent, 60-79 points were good, 40-59 points were fair, and <40 points were poor.Results:A total of 94 severed composite tissues in 35 patients, including of 20 male patients and 15 female patients were enrolled. The average age was 36.4 years (range, 16-65 years). Fifty severed tissues in 18 cases were classified into type Ⅰ, 40 severed tissues in 15 cases type Ⅱ, 4 severed tissues in 2 cases type Ⅲ. Among the 35 cases, 1 case of thumb pulp severed tissue was necrotic at the edge (0.3 cm×0.5 cm) due to local contusion, 1 case of index finger lateral severed tissue was necrotic at the edge (0.3 cm×0.8 cm) due to local avulsion injury, and healed after dressing change, and the other replanted composite tissue survived. The patients were followed up for 3 to 65 months (average, 18.5 months). The wounds were completely healed, and the color, elasticity, and quality of the replanted tissue was close to the surrounding normal skin. There was no obvious swelling or atrophy deformity of the hands. According to the patients’ self-assessment, 31 cases were satisfied and 4 cases were average. Comprehensive evaluation of hand function and appearance: excellent in 23 cases, good in 9 cases, fair in 3 cases, excellent and good rate was about 91.4% (32/35).Conclusion:Though multiple composite tissues replantation with microsurgical technique in single hand is difficult, and vascular anastomosis technical requirement is high, once surgery succeeds, the function and appearance can get good recovery, and patient satisfaction is also relatively high.