ObjectiveThis study aims to investigate the molecular mechanism by which Guizhi Fulingwan （GFW） inhibits ferroptosis in endometriosis （EMT） through the regulation of the hypoxia inducible factor-1α/heme oxygenase 1 （HIF-1α/HO-1） signaling pathway. MethodsMachine learning was employed to identify ferroptosis-related biomarkers associated with EMT. Network pharmacology was utilized to identify the active components of GFW and its potential therapeutic targets against EMT， including core targets. Functional enrichment analysis was conducted to explore the biological processes， molecular functions， cellular components， and signaling pathways associated with the potential targets. An EMT rat model was established via autologous transplantation. Thirty female Sprague-Dawley （SD） rats were randomly divided into five groups： sham-operated， model， positive control （dienogest at 0.2 mg·kg^-1）， low-dose GFW （2.5 g·kg^-1）， and high-dose GFW （5 g·kg^-1）. After modeling， the rats received their respective treatment by oral gavage for 28 consecutive days， while the sham and model groups received equal volumes of distilled water. Serum and ectopic endometrial tissues were collected. Hematoxylin and eosin （HE） staining was employed to evaluate morphological alterations in ectopic lesions. Quantitative real-time polymerase chain reaction （Real-time PCR） and Western blot were conducted to assess mRNA and protein expression of HIF-1α， HO-1， glutathione peroxidase 4 （GPX4）， spermidine/spermine N1-acetyltransferase （SAT1）， and prostaglandin-endoperoxide synthase 2 （PTGS2）. Tissue levels of malondialdehyde （MDA）， glutathione （GSH）， and ferrous iron （Fe²⁺） were quantified using commercial assay kits. Serum levels of interleukin-6 （IL-6） and transforming growth factor-β₁ （TGF-β₁） were measured via enzyme-linked immunosorbent assay （ELISA）. ResultsFive ferroptosis-related biomarkers in EMT were identified： ALOX12， CHAC1， SAT1， AST1， and HO-1. Network pharmacology analysis revealed 42 active components of GFW and 192 potential therapeutic target genes related to EMT treatment， with FOS， JUN， HO-1 identified as core targets. Functional enrichment analysis indicated that the potential targets were primarily involved in oxidative stress response and reactive oxygen species metabolism and were enriched in the HIF-1 signaling pathway. Compared to the sham-operated group， the model group exhibited significant increases in both mRNA and protein expression of HIF-1α， HO-1， and PTGS2， as well as elevated tissue levels of Fe²⁺ and MDA. Conversely， GSH levels and the expression of GPX4 and SAT1 were markedly reduced， and serum levels of IL-6 and TGF-β₁ levels were significantly higher （P<0.01）. Compared with the model group， all GFW-treated groups showed significant downregulation of HIF-1α and HO-1， reduced Fe²⁺ levels， and downregulated expression of MDA， PTGS2， IL-6， and TGF-β₁. Meanwhile， GSH， GPX4， and SAT1 expression levels were significantly increased （P<0.05， P<0.01）， effectively ameliorating iron overload and oxidative stress， thereby demonstrating therapeutic efficacy in EMT， with the high-dose GFW demonstrating the most pronounced therapeutic effects. ConclusionGFW exerts therapeutic effects on endometriosis by regulating the HIF-1α/HO-1 signaling pathway to rectify iron metabolism disorders and attenuate free iron-induced oxidative damage. It upregulates the antioxidative defense system to inhibit lipid peroxidation cascades and modulates inflammatory cytokine networks. These effects collectively disrupt the pathological interaction between ferroptosis and chronic inflammation， providing a novel theoretical foundation for the clinical application of GFW in EMT treatment.

Objective:To explore the relationship between mindfulness, optimism, and subjective well-being in post-lung transplantation patients, so as to provide a basis for nursing staff to improve patients' subjective well-being.Methods:This study was a cross-sectional survey. Convenience sampling was used to select 205 post-lung transplantation patients admitted to the First Affiliated Hospital of Guangzhou Medical University from October 2022 to November 2023 for the study. General Information Questionnaire, World Health Organization-Five Well-Being Scale, Mindful Attention Awareness Scale (MAAS) and Life Orientation Test-R (LOT-R) were used to investigate the study participants. Pearson correlation was used to analyze the correlation between subjective well-being and mindfulness and optimism in patients after lung transplantation. AMOS 24.0 software was used to construct a mediating model to analyze the path relationship between mindfulness, optimism and subjective well-being.Results:A total of 205 questionnaires were distributed and 202 valid questionnaires were recovered, with an effective recovery rate of 98.54% (202/205). In 202 patients after lung transplantation, the WHO-5 Well-Being Scale total score, MAAS total score, and LOT-R score were (16.31±4.73), (56.75±9.44), and (18.49±3.85), respectively. Lung transplantation patients' subjective well-being was positively correlated with mindfulness and optimism ( r=0.570, 0.600, both P<0.01). Optimism partially mediated the relationship between mindfulness and subjective well-being, with an effect value of 0.290 and an effect proportion of 52.35% (0.290/0.554) . Conclusions:Mindfulness and optimism are both positively correlated with subjective well-being in post-lung transplantation patients, and mindfulness could also influence subjective well-being through the mediating effect of optimism. Healthcare professionals should fully explore and cultivate positive psychological resources, such as mindfulness, in lung transplant patients, by increasing optimism as the target of intervention, which in turn improves patients' subjective well-being.

Objective:To explore the relationship between mindfulness, optimism, and subjective well-being in post-lung transplantation patients, so as to provide a basis for nursing staff to improve patients' subjective well-being.Methods:This study was a cross-sectional survey. Convenience sampling was used to select 205 post-lung transplantation patients admitted to the First Affiliated Hospital of Guangzhou Medical University from October 2022 to November 2023 for the study. General Information Questionnaire, World Health Organization-Five Well-Being Scale, Mindful Attention Awareness Scale (MAAS) and Life Orientation Test-R (LOT-R) were used to investigate the study participants. Pearson correlation was used to analyze the correlation between subjective well-being and mindfulness and optimism in patients after lung transplantation. AMOS 24.0 software was used to construct a mediating model to analyze the path relationship between mindfulness, optimism and subjective well-being.Results:A total of 205 questionnaires were distributed and 202 valid questionnaires were recovered, with an effective recovery rate of 98.54% (202/205). In 202 patients after lung transplantation, the WHO-5 Well-Being Scale total score, MAAS total score, and LOT-R score were (16.31±4.73), (56.75±9.44), and (18.49±3.85), respectively. Lung transplantation patients' subjective well-being was positively correlated with mindfulness and optimism ( r=0.570, 0.600, both P<0.01). Optimism partially mediated the relationship between mindfulness and subjective well-being, with an effect value of 0.290 and an effect proportion of 52.35% (0.290/0.554) . Conclusions:Mindfulness and optimism are both positively correlated with subjective well-being in post-lung transplantation patients, and mindfulness could also influence subjective well-being through the mediating effect of optimism. Healthcare professionals should fully explore and cultivate positive psychological resources, such as mindfulness, in lung transplant patients, by increasing optimism as the target of intervention, which in turn improves patients' subjective well-being.

Peptides are a particular molecule class with inherent attributes of some small-molecule drugs and macromolecular biologics, thereby inspiring continuous searches for peptides with therapeutic and/or agrochemical potentials. However, the success rate is decreasing, presumably because many interesting but less-abundant peptides are so scarce or labile that they are likely 'overlooked' during the characterization effort. Here, we present the biochemical characterization and druggability improvement of an unprecedented minor fungal RiPP (ribosomally synthesized and post-translationally modified peptide), named acalitide, by taking the relevant advantages of metabolomics approach and disulfide-bridged substructure which is more frequently imprinted in the marketed peptide drug molecules. Acalitide is biosynthetically unique in the macrotricyclization via two disulfide bridges and a protease (AcaB)-catalyzed lactamization of AcaA, an unprecedented precursor peptide. Such a biosynthetic logic was successfully re-edited for its sample supply renewal to facilitate the identification of the in vitro and in vivo antiparkinsonian efficacy of acalitide which was further confirmed safe and rendered brain-targetable by the liposome encapsulation strategy. Taken together, the work updates the mining strategy and biosynthetic complexity of RiPPs to unravel an antiparkinsonian drug candidate valuable for combating Parkinson's disease that is globally prevailing in an alarming manner.

Objective: To investigate protective effects of nicotinamide mononucleotide (NMN) on ethanol-induced DNA damage in L02 cells, so as to provide the evidence for adjuvant therapy of NMN on alcoholic liver diseases. Methods: L02 cells were pretreated with different concentrations of NMN (0, 1, 2, 4 and 8 mmol/L) for 6 h, and then were exposed to 0.4% ethanol for 12 h. The treated cells were divided into the control group, 0.4% ethanol group and different concentrations of NMN groups. Cell viability was analyzed using trypan blue staining for determining the concentration of NMN as a protective agent. The effects of NMN on ethanol-induced DNA damage in L02 cells were evaluated using immunofluorescence detection and reactive oxygen species (ROS) assay. L02 cells were exposed to 0.4% ethanol for 12 h, cultured in a medium containing a protective concentration of NMN, and divided into PBS group and NMN group. Cell viability was detected at 0, 2, 4, 8, 16 and 32 h, and the effects of NMN on repairing ethanol-induced DNA damage were evaluated by alkaline comet assay. Results: The cell viability was lower in 0.4% ethanol group than than in the control group, and was higher in different concentrations of NMN groups than in 0.4% ethanol group (all P<0.05), with no significant difference in the cells viability between 4 mmol/L and higher concentrations of NMN groups and the control group (all P>0.05). Therefore, 4 mmol/L NMN was selected as a protective agent. The cell tail moments, relative immunofluorescence intensities of γH2AX and relative levels of ROS were higher in 0.4% ethanol group than in the control group, and lower in 4 mmol/L and higher concentrations of NMN groups than in 0.4% ethanol group (all P<0.05). The cell viability was increased and the cell tail moment was shortened with the increase of 4 mmol/L NMN intervention time; and the cell viability in 4 h and more of NMN groups were higher, and the cell tail moment were lower than that in PBS group (all P<0.05). Conclusions NMN attenuates DNA damage in a dose-dependent manner and promotes the repair of DNA damage in a time-dependent manner. NMN has a protective effect on ethanol-induced DNA damage in hepatocytes.

Objective:To evaluate the clinical application efficacy of four-stitch cholangiojejunostomy.Methods:Of 38 patients who received four-needle biliary and enterointestinal anastomosis in the Department of Hepatobiliary Surgery, Yuebei People's Hospital Affiliated to Shantou University Medical College from November 2016 to April 2020 were included, and the diseases, surgical methods and postoperative complications of four-needle biliary and enterointestinal anastomosis were analyzed.Results:There were 26 males and 12 females with an average of 57.3(44-77) years. Among 38 patients, there were 12 hilar cholangiocarcinoma patients, 10 pancreatic head cancer, 9 duodenal papillary cancer, 4 intrahepatic and extrahepatic bile duct stones, 1 pancreatic cystic adenoma, 1 gastric cancer invading pancreatic head and 1 gallbladder carcinoma. The procedure included pancreatoduodenectomy in 20, radical resection of hilar cholangiocarcinoma in 12, hepatectomy with biliary-enteric anastomosis in 4, radical resection of gastric cancer combined with pancreaticoduodenectomy in 1, radical resection of gallbladder carcinoma in 1. One, two and three ductal openings were anastomosed in 27, 7 and 4 patients, respectively. 10 patients have bile duct diameter <6 mm. Postoperative anastomotic leakage occurred in 1, and all patients were received followed-up visit for 2 months to 4 years without anastomotic stenosis.Conclusion:Four-stitch cholangiojejunostomy is simple, safe, effective, and convenient for small biliary ductal surgeries.

OBJECTIVE：To reference for the rational use of sodium va lproate in clinic. METHODS ：By retrospective analysis，blood concentration monitoring results of sodium valproate and medical record data in 856 patients were collected from the Affiliated Tianyou Hospital of Wuhan University of Science and Technology during Jan. 2016-Dec. 2018. The dosage form of sodium valproate ，monitoring times of therapeutic drugs ，monitoring results of steady-state blood concentration of sodium valproate up to the standard ，dosage adjustment and the combination with carbamazepin ，fluconazol and carbapenem drugs were analyzed. Fisher exact test was used to analyze the factors influencing the steady-state blood concentration of sodium valproate up to the standard. RESULTS ：A total of 1 270 cases of sodium valproate were monitored in 856 patients，involving 407 males and 449 females，with age of （38.2±13.8）years and body mass of （52.3±10.0）kg. Among 1 270 cases of monitoring ，steady-state blood concentration of sodium valproate in 554 cases were in the range of 50-100 µg/mL，and 43.6％ of which reached the standard. The rate of reaching the standard in patients with multiple monitoring was higher than patients with single monitoring ；the dosage of patients with last monitoring reaching the standard was higher than that of patients with the first monitoring reaching the standard. The rate of reaching the standard in Sodium valproate sustained-release tablet group was higher than general Sodium valproate tablet group；the carbamazepin/fluconazol free group was higher than the carbamazepin combination group and fluconazol combination group；the carbapenem free group was higher than the carbapenem combination group （all P＜0.05）. CONCLUSIONS ：Clinical pharmacists should pay attention to the monitoring of sodium valproate treatment drugs ， strengthen the publicity and 3551851542@qq.com education of patients and their families ，and try to use Sodium valproate sustained-release tablets. When patients additionally receive carbapenem drugs like carbamazepin or fluconazol ， the standard level of sodium valproate will be reduced ，then the dosage of sodium valproate should be adjusted.

Objective:To review the clinical efficacy and safety of the FOLFIRINOX (oxaliplatin, irinotecan, leucovorin, fluorouracil) regimen in treatment of pancreatic cancer.Methods:The clinical data of 31 patients with pancreatic cancer who were treated with the FOLFIRINOX regimen from July 2016 to December 2019 at the Department of General Surgery, China-Japan Friendship Hospital were retrospectively analyzed. For the 20 males and 11 females who were enrolled into this study, their age ranged from 29 to 80 years (mean 56.9 years). The FOLFIRINOX regimen was used as neoadjuvant therapy in 12 patients, postoperative therapy in 10 patients with liver-metastases, and postoperative adjuvant therapy in 9 patients (as second-line chemotherapy in 7 patients and as first-line chemotherapy in 2 patients). The clinical efficacy and adverse reactions of chemotherapy were evaluated.Results:In this study, 8 patients received the modified FOLFIRINOX regimen. Of the remaining 23 patients who received the standard FOLFIRINOX regimen, 10 (43.3%) were converted to the modified regimen because of adverse events. On clinical efficacy evaluation after neoadjuvant therapy: 5 patients achieved partial remission (PR), 3 stable disease (SD) and 4 progression disease (PD). The disease control rate (DCR) was 66.7% (8/12). For 10 patients got remission of abdominal pain, 5 patients underwent surgical resection. For the 10 patients with liver-metastases, 6 achieved PR, 1 SD, 3 PD. For 7 patients got disease control. For 8 patients had remission of abdominal pain, 1 patient underwent surgical resection. For the 7 patients who received second-line chemotherapy, 2 achieved PR and 5 PD. No tumor recurrence or metastases were found in the two patients after the first-line chemotherapy. Adverse events above grade three in all the patients included neutropenia in 12 patients (38.7%), leukopenia in 7 patients (22.6%) and thrombocytopenia in 1 patient (3.2%).Conclusions:The FOLFIRINOX regimen was efficacious with a high DCR rate and controllable adverse events. Balancing its efficacy and safety showed this regimen to be beneficial to patients with pancreatic cancer.

Brain ; pathology ; China ; Humans ; Organ Preservation ; standards ; Tissue Banks ; ethics ; standards

Tung tree (Vernicia fordii) is an economically important woody oil plant that produces tung oil rich in eleostearic acid. Here, we report a high-quality chromosome-scale genome sequence of tung tree. The genome sequence was assembled by combining Illumina short reads, Pacific Bio-sciences single-molecule real-time long reads, and Hi-C sequencing data. The size of tung tree gen-ome is 1.12 Gb, with 28,422 predicted genes and over 73％ repeat sequences. The V. fordii underwent an ancient genome triplication event shared by core eudicots but no further whole-genome duplication in the subsequent ca. 34.55 million years of evolutionary history of the tung tree lineage. Insertion time analysis revealed that repeat-driven genome expansion might have arisen as a result of long-standing long terminal repeat retrotransposon bursts and lack of efficient DNA deletion mechanisms. The genome harbors 88 resistance genes encoding nucleotide-binding sites;17 of these genes may be involved in early-infection stage of Fusarium wilt resistance. Further, 651 oil-related genes were identified, 88 of which are predicted to be directly involved in tung oil biosynthesis. Relatively few phosphoenolpyruvate carboxykinase genes, and synergistic effectsbetween transcription factors and oil biosynthesis-related genes might contribute to the high oil content of tung seed. The tung tree genome constitutes a valuable resource for understanding genome evolution, as well as for molecular breeding and genetic improvements for oil production.