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 investigate the ameliorative effects of Imperatae Rhizoma （RI） extract against doxorubicin （DOX）-induced myocardial injury and its potential molecular mechanisms. METHODS Network pharmacology was employed to screen for target overlap between the predicted core targets of RI’s active components and targets associated with myocardial injury， followed by gene ontology （GO） and Kyoto Encyclopedia of Genes and Genomes （KEGG） enrichment analyses. Based on the network pharmacology results， a DOX-induced myocardial injury mouse model was established using male C57BL/6J mice to observe the effects of RI extract [1 g/（kg·d）] on the survival rate， body weight， and cardiac damage. A DOX-injured HL-1 cardiomyocyte model was established to assess the effects of different mass concentrations of RI extract （50， 100， 200 μg/mL） on mitochondrial membrane potential， adenosine triphosphate （ATP） production， reactive oxygen species （ROS） generation， apoptosis， and expression of the relevant target proteins. The mechanism was validated by transfecting with small interfering RNA of estrogen receptor 1 （ESR1）. RESULTS A total of 58 overlapping targets were screened， which were enriched in biological processes such as hormone response and hypoxia response， as well as pathways including apoptosis， tricarboxylic acid cycle， and pyruvate metabolism. Key target proteins， such as ESR1， were also identified. Animal experiments confirmed that the survival rate of mice in the DOX+RI group was obviously higher than that in the DOX group， with a slower rate of weight loss and improved pathological changes， such as cardiac atrophy and inflammatory cell infiltration， compared to the DOX group. Cell experiments showed that， compared with the DOX group， the DOX+RI groups exhibited significantly increased or upregulated mitochondrial membrane potential， relative ATP levels， and mRNA expressions of isocitrate dehydrogenase 3A （IDH3A）， succinate dehydrogenase A （SDHA） and peroxisome proliferators-activated receptor γ coactivator-1α （PGC-1α）， as well as mRNA and protein expressions of ESR1； conversely， relative ROS levels and apoptosis rates were significantly reduced （ P ＜0.05）. Following ESR1 knockdown， the anti-apoptotic effect of the RI extract on cardiomyocytes was significantly attenuated （ P ＜0.05）. CONCLUSIONS The RI extract may alleviate DOX-induced myocardial injury by activating the ESR1 signaling pathway， improving mitochondrial function， and inhibiting excessive ROS production and cardiomyocyte apoptosis.

Objective To explore the therapeutic effect and mechanism of umbilical cord mesenchymal stem cells (UC-MSC) in rats with primary graft dysfunction after lung transplantation. Methods Twenty-four male Lewis rats were randomly divided into donor and recipient groups, with 12 rats in each group. The recipients were further divided into 3 groups: blank control group, negative control group, and treatment group, with 4 rats in each group. The color, size and texture of the transplanted lungs were observed 72 h after lung transplantation. The ventilation status and progression of consolidation in the transplant lungs of rats in each group were evaluated by micro-CT. Plasma, transplant lung tissue and alveolar lavage fluid samples of recipient rats were collected. The wet/dry ratio of lung tissue was measured to evaluate the degree of pulmonary edema. Hematoxylin-eosin (HE) staining was used to evaluate the degree of lung tissue damage. Terminal deoxyribonucleic acid transferase mediated dUTP nick end labeling (TUNEL) staining was used to evaluate cell apoptosis. Myeloperoxidase (MPO) activity in lung tissue was detected, and enzyme-linked immunosorbent assay (ELISA) was used to detect interleukin (IL)-6, IL-10 and tumor necrosis factor (TNF)-α levels in plasma and alveolar lavage fluid. Results The appearance of the transplant lungs in the negative control group was significantly different from that of the autologous lungs, while the transplant lungs in the treatment group were almost identical in color to the autologous lungs compared to the blank control group. Compared with the negative control group, the treatment group showed reduced alveolar exudate and more intact airway epithelial cell structure. No alveolar exudate was observed in the blank control group, and the structure of the airways and alveoli remained normal. The treatment group had lower apoptosis rate of airway epithelial cells, lung tissue wet/dry ratio, and MPO activity compared to the negative control group (all P < 0.05). The levels of IL-6 and TNF-α in the bronchoalveolar lavage fluid of the treatment group were lower than those in the negative control group, while the level of IL-10 was higher than that in the negative control group and the blank control group (all P < 0.05). There were no statistically significant differences in the levels of cytokines in plasma among each group (all P > 0.05). Conclusions UC-MSC may effectively alleviate the severity of primary graft dysfunction in rats by reducing the apoptosis rate of cells in lung tissue and inhibiting inflammatory responses.

Objective:To compare the clinical outcomes and costs in arthroscopic repair of small and medium-sized supraspinatu tendon tears between double-pulley suture-bridge (DPSB) and traditional suture bridge (SB).Methods:A retrospective study was conducted at Department of Joint Surgery, The Second Hospital Affiliated to Hengyang Medical School to analyze the data of 26 patients with small and medium-sized supraspinatus tendon tears who had been treated by SB repair from May 2018 to December 2020 (SB group) and those of 35 patients with small and medium-sized supraspinatus tendon tears who had been treated by DPSB repair from January 2021 to December 2022 (DPSB group). There were 61 patients in the 2 groups, including 44 males and 17 females, with an age of (59.1±7.5) years. The left shoulder was affected in 26 patients and the right shoulder in 35 patients. The tear size was small in 25 cases and medium in 36 ones. The total number of anchors used, total anchoring costs, and surgical time were recorded and compared between the 2 groups. Visual analogue scale (VAS), American Shoulder and Elbow Surgeons (ASES) score, University of California Los Angeles (UCLA) score and shoulder range of motion were used to evaluate the clinical outcomes of the 2 groups before surgery and at the last follow-up. Comparisons were made within and between the 2 groups. Tendon integrity was assessed using MRI or ultrasound at 3, 6, 12 months or at the last follow-up.Results:There was no statistically significant difference in the preoperative general data between the 2 groups, indicating comparability ( P>0.05). DPSB and SB groups were followed up for (28.1±3.5) and (27.1±1.8) months, respectively. There was no statistically significant difference between DPSB group and SB group in surgical time or total number of anchors ( P>0.05). The total costs of anchoring in DPSB group [(6,028.6±173.4) yuan] were significantly lower than those in SB group [(13,257.1±554.2) yuan] ( P<0.05). At the last follow-up, the anterior flexion, abduction, external rotation and internal rotation of the shoulder, as well as VAS pain score, ASES score and UCLA score, were significantly better in both DPSB group and SB group than their preoperative values ( P<0.05), but there were no statistically significant differences between DPSB group and SB group ( P>0.05). There was no significant difference either in tendon retear between DPSB group (2 cases) and SB group (1 case) ( P>0.05). No such complication as wound infection or nerve damage was found in either group. Conclusions:In arthroscopic repair of small and medium-sized supraspinatu tendon tears, both DPSB and SB techniques can achieve satisfactory and comparable clinical outcomes. However, DPSB leads to lower total costs of anchoring.

Objective:To investigate the clinical value of 18F-NaF PET/CT coronary plague imaging in evaluating the long-term prognosis of patients with coronary artery disease (CAD). Methods:A retrospective cohort study was conducted among 54 patients (37 males and 17 females, aged (57.2±9.8) years) diagnosed with CAD from a multicenter study between September 2015 and October 2022. All patients underwent 18F-NaF PET/CT and coronary angiography (CAG) within 1 week, and the PET/CT imaging was performed at the First Hospital of Shanxi Medical University. Major adverse cardiovascular events (MACE) were followed up. ROC curves were established to obtain the optimal thresholds of SUV max and accumulated SUV max of all lesions of main coronary artery branches (S-SUV max) for predicting MACE. Cox proportional risk model and Kaplan-Meier method (log-rank test) were used to analyze the predictive value of PET parameters for MACE. Differences in metabolic parameters between 2 groups were compared by Mann-Whitney U test. Results:The median follow-up time of the 54 patients was 6.0(1.8, 6.6) years, and 13(24.1%) patients developed MACE, including 7 deaths, 5 myocardial infarction and 1 severe arrhythmia. S-SUV max in MACE group was significantly higher than that in the non-MACE group (2.64(2.08, 4.49) vs 1.83(0.95, 2.90); Z=-2.04, P=0.041). ROC curve showed that the optimal threshold of S-SUV max for MACE prediction was 2.05 (AUC=0.690). Multivariate Cox analysis showed that S-SUV max was a strong predictor of MACE (hazard ratio ( HR)=2.434(95% CI: 1.547-3.828), P<0.001). ROC curve showed that the optimal threshold of SUV max to predict MACE was 0.55 (AUC=0.659), and univariate Cox analysis showed that SUV max was a factor to predict MACE ( HR=10.192 (95% CI: 2.667-38.953), P=0.001). In 25 patients with incomplete revascularization (ICR), Kaplan-Meier analysis showed that the incidence of MACE in patients with positive 18F-NaF uptake (single medium stenosis (40%-70%) with SUV max≥0.55) was significantly higher than that in patients with negative 18F-NaF uptake (5/14 vs 0/11; χ2=6.07, P=0.014). Conclusions:18F-NaF PET/CT can be used as an independent predictor of MACE in patients with CAD and can quantitatively assess the long-term progression of moderate coronary artery stenosis. In the future, it is expected to be a new non-invasive way to guide the revascularization treatment decision of multi-vessel CAD.

Hematopoietic stem cell transplantation (HSCT) is currently an effective method to cure hematologic malignancies and bone marrow failure diseases, and can restore hematopoietic function destroyed by hematologic malignant diseases. In recent years, HSCT has developed rapidly in China, but pulmonary chronic graft-versus-host disease after transplantation has seriously affected the quality of life and long-term survival of patients. Therefore, this article aims to describe the risk factors, clinical classification, and early diagnosis and treatment strategies of pulmonary chronic graft-versus-host disease, and proposes that lung transplantation is the only effective therapeutic intervention when medical treatment proves ineffective for end-stage pulmonary cGVHD.

Whole-genome sequencing, serotype typing, MLST typing, population genetic structure analysis, and core-genome single nucleotide polymorphism (cgSNP) analysis were performed on 23 strains of mucoid Haemophilus influenzae collected from the Laboratory Center of Hunan Children′s Hospital from January 2021 to December 2022. Drug susceptibility tests were conducted using the automated microbial identification and susceptibility analysis system AF-600, and virulence genes and drug resistance genes were analyzed based on the whole-genome sequences. Based on the serotype typing of whole-genome sequencing, all 23 strains were Haemophilus influenzae type b (Hib). MLST analysis revealed that the 23 strains belonged to six ST types, among which 10 strains (43.5%) were ST386, 5 strains (21.7%) were ST18, and 2 strains (8.7%) were the newly discovered ST2887. Bayesian population structure analysis (BAPS) showed three distinct populations. The results of the virulence gene analysis showed that the carriage rates of genes encoding capsule-related proteins and those associated with bacterial immune regulation and inflammatory signaling pathways were all 100%. However, the ompP5 gene related to bacterial adhesion, and the hgpC and hxuA genes related to bacterial protein metabolism were all present in the newly discovered ST2887. The in vitro drug susceptibility test results of 23 strains of mucoid Hib showed that the resistance rates to ampicillin, cefuroxime, and Trimethoprim-sulfamethoxazole were 13.0%(3 strains), 13.0%(3 strains), and 87.0%(20 strains), respectively. They were sensitive to other beta-lactam drugs. All the 23 strains of mucoid Haemophilus influenzae infected children were Hib, and the main ST types were ST386 and ST18. It is very important to advocate Hib vaccination.

Background and Aims:Precise localization of lesions and optimization of the surgical approach are crucial in laparoscopic left hepatectomy.Traditional surgical techniques have certain limitations,whereas indocyanine green(ICG)fluorescence navigation can accurately delineate the boundaries of liver lesions.The Laennec's capsule approach aids in clearly exposing intrahepatic structures.This study was conducted to evaluate the clinical effectiveness of combining ICG fluorescence navigation with the Laennec's capsule approach in laparoscopic left hepatectomy.Methods:The clinical data of 44 liver cancer patients who underwent surgery at the Hepatobiliary Surgery Department of Xuanhan People's Hospital from January 2023 to November 2024 were retrospectively collected.Among them,22 patients underwent laparoscopic left hepatectomy with Pringle's maneuver for total hepatic inflow occlusion(control group),while the other 22 patients received laparoscopic left hepatectomy using ICG fluorescence navigation combined with the Laennec's capsule approach(observation group).The two groups were compared in terms of intraoperative surgical time,average blood loss,intraoperative transfusion rate,liver function on postoperative days(POD)1,3,and 7[total bilirubin(TBIL),aspartate aminotransferase(AST),alanine aminotransferase(ALT)],average length of hospital stay,gastrointestinal function recovery time,POD 1-6 drainage volume,incidence of postoperative complications,and short-term efficacy.Results:The observation group had significantly shorter average surgical time than the control group[(218.19±39.18)min vs.(245.23±44.36)min,P＜0.05]and less average blood loss[(320.44±78.62)mL vs.(456.37±88.16)mL,P＜0.05].The intraoperative transfusion rate between the two groups was not significantly different(13.64％vs.9.09％,P＞0.05).The observation group had significantly less postoperative drainage POD 1-6 than the control group[(431.19±152.18)mL vs.(528.23±184.36)mL,P＜0.05].The average hospital stay and gastrointestinal function recovery time were shorter in the observation group[(9.21±2.92)d vs.(12.72±3.24)d;(2.24±0.42)d vs.(3.35±0.53)d,both P＜0.05].Postoperative liver function tests(TBIL,AST,ALT)on days 1,3,and 7 were significantly lower in the observation group compared to the control group(all P＜0.05).The difference in the overall response rate between the two groups was not statistically significant(72.73％vs.77.27％,P＞0.05).No severe postoperative complications occurred in either group.Conclusion:The combination of ICG fluorescence navigation with the Laennec's capsule approach demonstrates favorable clinical outcomes in laparoscopic left hepatectomy and is worthy of clinical promotion.

Objective:To investigate the effects of transhepatic arterial chemoembolization(TACE)combined with Endostar on CD4+/CD8+T cells,5-aminoketovalonate synthase 1(ALAS1)and HIPPO-YAP signaling pathway in patients with hepatocellular carcinoma(HCC).Methods:A total of 60 HCC patients admitted to Chengdu Third People's Hospital from January 2018 to December 2021 were enrolled and randomly divided into TACE treatment group(A)and TACE combined with Endostar treatment group(B),with 30 patients in each group.T lymphocyte,ALAS1 and indicators of HIPPO-YAP signaling pathway were observed in the two groups.Results:In group A,1 subject had complete remission,2 subjects had partial remission,2 subjects had stable remission,and 4 subjects had progress;in group B,2 subjects had complete remission,4 subjects had partial remission,4 subjects had stable remis-sion,and 1 subject had progress.The total effective rate in group B(33.33%)was significantly higher than that in group A(10.00%),with significant difference among groups(P=0.028).There were no significant differences in CD4+T cells,CD8+T cells and CD4+/CD8+T cells between the two groups before treatment(P=0.972,0.995,0.917).After treatment,level of CD4+T cells in the two groups was significantly increased(P<0.001),while level of CD8+T cells was significantly decreased(P<0.001).CD4+/CD8+T cells was significantly increased(P<0.001),and the changes in group B were significant compared with group A(P<0.001).There was no significant difference in content of ALAS1 between the two groups before treatment(P=0.975);after treatment,content of ALAS1 in liver cancer tissues of the two groups was significantly increased(P<0.001),which in group B was significantly higher than that in group A(P<0.05).Before treatment,there were no significant differences in mammalian STE20-like protein kinase 2(MST2),large tumor suppressor 1(LATS1)and Yes-associated protein(YAP)between the two groups(P=0.134,0.134,0.134).After treatment,mRNA relative expressions of MST2 and LATS1 were significantly increased(all P<0.001),while mRNA relative expression of YAP were significantly decreased(P<0.001),and changes of group B were significant compared with group A(all P<0.001).After treat-ment,there were 5 more cases of no adverse reactions in group B than in group A,and the total incidence of adverse reactions(16.67%)was significantly lower than that in group A(43.33%),with a significant difference between groups(P=0.024).Conclu-sion:TACE combined with Endostar has significant therapeutic effect on HCC patients,which can effectively regulate CD4+/CD8+T cells,promote ALAS1 secretion,and activate HIPPO-YAP signaling pathway.

Objective To summarize the clinical experience of the first case of sulbactam-durlobactam treatment for extensively drug-resistant Acinetobacter baumannii infection after lung transplantation in China.Methods A retrospective analysis was conducted on a case of a patient with severe chronic obstructive pulmonary disease who received sulbactam-durlobactam treatment after lung transplantation.Results A 68-year-old male patient with a history of drug-resistant Acinetobacter baumannii infection before surgery,experienced worsening infection and impaired renal function after lung transplantation,with sputum culture showing extensively drug-resistant Acinetobacter baumannii.After receiving combination treatment with sulbactam-durlobactam and meropenem,the infection was controlled,and the function of the transplanted lung was restored.Conclusions Sulbactam-durlobactam has potential therapeutic value for extensively drug-resistant Acinetobacter baumannii infection after lung transplantation and provides a new strategy for clinical practice.