OBJECTIVE: To investigate the effects of Danmu Extract Syrup (DMS) on lipopolysaccharide (LPS)-induced acute lung injury (ALI) in mice and explore the mechanism. METHODS: Seventy-two male Balb/C mice were randomly divided into 6 groups according to a random number table (n=12), including control (normal saline), LPS (5 mg/kg), LPS+DMS 2.5 mL/kg, LPS+DMS 5 mL/kg, LPS+DMS 10 mL/kg, and LPS+Dexamethasone (DXM, 5 mg/kg) groups. After pretreatment with DMS and DXM, the ALI mice model was induced by LPS, and the bronchoalveolar lavage fluid (BALF) were collected to determine protein concentration, cell counts and inflammatory cytokines. The lung tissues of mice were stained with hematoxylin-eosin, and the wet/dry weight ratio (W/D) of lung tissue was calculated. The levels of tumor necrosis factor-α (TNF-α), interleukin (IL)-6 and IL-1 β in BALF of mice were detected by enzyme linked immunosorbent assay. The expression levels of Claudin-5, vascular endothelial (VE)-cadherin, vascular endothelial growth factor (VEGF), phospho-protein kinase B (p-Akt) and Akt were detected by Western blot analysis. RESULTS: DMS pre-treatment significantly ameliorated lung histopathological changes. Compared with the LPS group, the W/D ratio and protein contents in BALF were obviously reduced after DMS pretreatment (P<0.05 or P<0.01). The number of cells in BALF and myeloperoxidase (MPO) activity decreased significantly after DMS pretreatment (P<0.05 or P<0.01). DMS pre-treatment decreased the levels of TNF-α, IL-6 and IL-1 β (P<0.01). Meanwhile, DMS activated the phosphoinositide 3-kinase/protein kinase B (PI3K/Akt) pathway and reversed the expressions of Claudin-5, VE-cadherin and VEGF (P<0.01). CONCLUSIONS DMS attenuated LPS-induced ALI in mice through repairing endothelial barrier. It might be a potential therapeutic drug for LPS-induced lung injury.
Mice ; Male ; Animals ; Proto-Oncogene Proteins c-akt/metabolism* ; Lipopolysaccharides ; Phosphatidylinositol 3-Kinases/metabolism* ; Interleukin-1beta/metabolism* ; Vascular Endothelial Growth Factor A/metabolism* ; Tumor Necrosis Factor-alpha/metabolism* ; Claudin-5/metabolism* ; Acute Lung Injury/chemically induced* ; Lung/pathology* ; Interleukin-6/metabolism* ; Drugs, Chinese Herbal

Intracellular overexpression of cytoglobin (Cygb) has been shown to reduce extracellular matrix deposition and promote liver fibrosis recovery, but its mechanism is not yet clear. This study constructed and expressed a fusion protein (TAT-Cygb) of cell penetrating peptide TAT and Cygb, to investigate the effect of fusion protein TAT-Cygb on regulating hepatic stellate cells (HSCs) ferroptosis. Cultured human hepatic stellate cells line (LX2) were treated with TAT-Cygb and erastin in vitro, respectively. The effects of ferroptosis phenotype in LX2 cells induced by TAT-Cygb, including cell viability, cell morphology, iron ion (Fe²⁺) content, lipid peroxidation product levels, and antioxidant system indicators, were investigated using trypan blue staining, transmission electron microscopy, Prussian blue staining, and reagent kits detection. After co-treatment with TAT-Cygb and ferrostain-1, the levels of Fe²⁺, reactive oxygen species (ROS), malondialdehyde (MDA), 4-hydroxynonenal (4-HNE), nicotinamide adenine dinucleotide phosphate (NADPH) and glutathione (GSH) were measured by reagent kits. The protein expression levels of alpha smooth actin (α-SMA), collagen I and fibronectin were detected by Western blot, and the protein expression level of epidermal growth factor receptor (EGFR) and desmin relevant to fibrosis were observed by immunofluorescence. The results showed that TAT-Cygb could significantly reduce the viability of LX2 cells and trigger events relevant to ferroptosis, including promoting intracellular Fe²⁺ accumulation, and inducing mitochondrial morphological changes, and intensifying lipid peroxidation products accumulation, and decreasing the level of antioxidant indexes, which played a similar role as erastin; Fer-1 significantly weakened the increase in Fe²⁺, ROS, MDA, 4-HNE levels induced by TAT-Cygb, as well as the decrease in NADPH and GSH levels, while also weakening the TAT-Cygb-induced over-expression levels of α-SMA, collagen I and fibronectin, and TAT-Cygb-induced under-expression levels of EGFR and desmin. This cellular level study indicated that TAT-Cygb can induce ferroptosis of activated HSCs. This study revealed the potential mechanism of TAT-Cygb anti-liver fibrosis, and provided the experimental basis for further research on the molecular mechanism of TAT-Cygb realizing biological function by regulating the ferroptosis pathway.

Objective:To investigate the clinical outcome of biplanar botulinum toxin type A injection in alleviating platysmal bands.Methods:From November 2022 to May 2023, the clinical data of patients with platysmal bands treated by botulinum toxin type A injection in Department of Face and Neck Plastic Surgery, Plastic Surgery Hospital, Chinese Academy of Medical Sciences, and Department of Plastic Surgery, Chengdu Badachu Cosmetic Hospital were retrospectively analyzed. The platysmal bands were marked, while patients were grinning, before injection. Using a 13 mm 30 G needle, 20 U/ml botulinum toxin was injected into the muscle layer along the bands from the clavicle direction. The dose was 1 U at a single point every 1.5 cm. Using a 3 mm 30 G needle, 10 U/ml botulinum toxin was injected into the deep surface of dermis along the bands with a single point dose of 0.5 U. Effects were evaluated by overall subjective satisfaction of patients, which were categorized into 4 grades: very satisfied, satisfied, dissatisfied, very dissatisfied. In addition, accessment by a third-party physician with global aesthetic improvement scale (GAIS) (1-5 points, the lower the score, the more significant the improvement is) and Geister platysmal band scale (0-4 points, the higher the score, the more severe the platysmal band is). Normal distribution data was represented by Mean±SD.Results:A total of 19 patients were included, including 3 males and 16 females, with the average age of 36.1 years. After a mean follow-up of 1.3 months (1-5 months), the overall subjective satisfaction was 100%(19/19). The GAIS score of third-party physicians was 1.12±0.33. 100%(19/19) of patients received a rating over moderate improvement(significant improvement in 17 cases and moderate improvement in 2 cases). The Geister platysmal band score decreased from preoperative 3.65 ± 0.33 to postoperative 0.76 ± 0.44. No serious complications were found except 5 cases of local congestion and 2 cases of injection pain, which were relieved in 1 week and 3 hours respectively. 2 cases felt mild neck weakness, but neck activity was not affected. The adverse symptoms all completely resolved spontaneously within 4 weeks. All patients have no mouth deviation, difficulty speaking, facial paralysis, allergies, or other noticeable complications.Conclusion:The injection of botulinum toxin type A in dual-plane of platysmal intramuscular layer and deep intradermal layer can effectively alleviate platysmal bands and achieve neck rejuvenation.

Objective:To investigate the clinical outcome of biplanar botulinum toxin type A injection in alleviating platysmal bands.Methods:From November 2022 to May 2023, the clinical data of patients with platysmal bands treated by botulinum toxin type A injection in Department of Face and Neck Plastic Surgery, Plastic Surgery Hospital, Chinese Academy of Medical Sciences, and Department of Plastic Surgery, Chengdu Badachu Cosmetic Hospital were retrospectively analyzed. The platysmal bands were marked, while patients were grinning, before injection. Using a 13 mm 30 G needle, 20 U/ml botulinum toxin was injected into the muscle layer along the bands from the clavicle direction. The dose was 1 U at a single point every 1.5 cm. Using a 3 mm 30 G needle, 10 U/ml botulinum toxin was injected into the deep surface of dermis along the bands with a single point dose of 0.5 U. Effects were evaluated by overall subjective satisfaction of patients, which were categorized into 4 grades: very satisfied, satisfied, dissatisfied, very dissatisfied. In addition, accessment by a third-party physician with global aesthetic improvement scale (GAIS) (1-5 points, the lower the score, the more significant the improvement is) and Geister platysmal band scale (0-4 points, the higher the score, the more severe the platysmal band is). Normal distribution data was represented by Mean±SD.Results:A total of 19 patients were included, including 3 males and 16 females, with the average age of 36.1 years. After a mean follow-up of 1.3 months (1-5 months), the overall subjective satisfaction was 100%(19/19). The GAIS score of third-party physicians was 1.12±0.33. 100%(19/19) of patients received a rating over moderate improvement(significant improvement in 17 cases and moderate improvement in 2 cases). The Geister platysmal band score decreased from preoperative 3.65 ± 0.33 to postoperative 0.76 ± 0.44. No serious complications were found except 5 cases of local congestion and 2 cases of injection pain, which were relieved in 1 week and 3 hours respectively. 2 cases felt mild neck weakness, but neck activity was not affected. The adverse symptoms all completely resolved spontaneously within 4 weeks. All patients have no mouth deviation, difficulty speaking, facial paralysis, allergies, or other noticeable complications.Conclusion:The injection of botulinum toxin type A in dual-plane of platysmal intramuscular layer and deep intradermal layer can effectively alleviate platysmal bands and achieve neck rejuvenation.

Objective To propose strategies for developing clinical predictive models,aiming to assist researchers in conducting standardized clinical prediction model studies.Methods Literature review was conducted to summarize the operational steps and content for developing clinical predictive models.Then,a methodological framework was summarized and refined through expert consultation.Results The 11-step methodological framework for developing clinical predictive models was obtained by synthesizing the experience of 456 clinical predictive modeling studies and expert consultation,and the details were analyzed and elaborated.Conclusions This study presents methodological strategies and recommendations for the development of clinical predictive models,intended to serve as a guide for researchers.

Objective:To investigate the expression pattern of the D930020B18Rik gene in the testis of the mouse in different stages of development and its possible role in spermatogenesis.Methods:Using gene expression profile microarray,we identified highly ex-pressed D930020B18Rik in the mouse testis and analyzed the expression pattern of the gene by qPCR,immunohistochemistry,Western blot and immunofluorescence staining,and verified its function and molecular mechanism using bioinformatics analysis,dual-luciferase reporter assay and cell cycle synchronization.Results:The expression of the D930020B18Rik gene remained low in the testis of the mouse and mainly localized in the cytoplasm of spermatogonia during the first 2 postnatal weeks(PNW),increased from the 3rd PNW to sexual maturity,localized in the cytoplasm of spermatogonia and the nuclei of round and elongated spermatids,but was absent in the nuclei of mature sperm.Phylogenetic analysis showed that the D930020B18Rik protein sequence was highly conserved in mammals.Gene set enrichment analysis indicated that D930020B18Rik and its homologous protein might be involved in regulating spermatogenesis of mammals by participating in nucleoplasmic condensation(normalized enrichment score[NES]=1.652,P＜0.01,false discov-ery rate[FDR]=0.153),meiosis(NES=1.960,P＜0.01,FDR=0.001)and formation of microtubule cytoskeleton during mitosis(NES=1.903,P＜0.01,FDR=0.009).Dual-luciferase reporter assay revealed that the transcription factors klf5 and foxo1 could identify and bind D930020B18Rik promoters and perform the function of positive or negative transcriptional regulation.Conclusion:The D930020B18Rik gene is expressed in the mouse testis in a time-and location-specific manner,highly associated with spermiogenesis,mainly localized in the nuclei of germ cells,and may be involved in the meiosis of spermatocytes and spermiogenesis.

Ovarian cancer, notable for its severe prognosis among gynecologic cancers, has seen substantial progress in treatment approaches recently. Enhanced protocols in chemotherapy and the introduction of poly (ADP-ribose) polymerase (PARP) inhibitors for maintenance therapy have markedly improved outcomes for patients with specific genetic profiles, such as those positive for BRCA mutations or exhibiting homologous recombination deficiency (HRD). Additionally, the method of intraperitoneal chemotherapy administration has emerged as a valuable alternative to traditional transvenous routes, showing promise for wider clinical adoption. The field of surgery has also evolved, with increasing exploration into the benefits and feasibility of laparoscopic methods over more invasive traditional surgeries, aiming for complete tumor removal but with reduced patient impact. The hereditary nature of ovarian cancer underscores the importance of genetic testing, which has become integral in tailoring treatment strategies, particularly in determining suitability for PARP inhibitors.The formation of the East Asian Gynecologic Oncology Trial Group (EAGOT) aims to optimize treatment across Japan, Korea, China, and Taiwan. The ovarian cancer committee of EAGOT shared the current policies, focusing on 5 topics: 1) strategies for maintenance therapy after initial surgery and chemotherapy, 2) drug regimens for platinum-sensitive and platinum-resistant recurrence, 3) intraperitoneal chemotherapy, 4) laparoscopic surgery as an alternative to laparotomy, and 5) current status of genetic testing (BRCA, HRD, and panel tests) for ovarian cancer and its prospects. EAGOT’s multi-national trials aim to harmonize these evolving treatment strategies, ensuring that the latest and most effective protocols are accessible across the region, thereby significantly impacting patient outcomes in East Asia.

Ovarian cancer, notable for its severe prognosis among gynecologic cancers, has seen substantial progress in treatment approaches recently. Enhanced protocols in chemotherapy and the introduction of poly (ADP-ribose) polymerase (PARP) inhibitors for maintenance therapy have markedly improved outcomes for patients with specific genetic profiles, such as those positive for BRCA mutations or exhibiting homologous recombination deficiency (HRD). Additionally, the method of intraperitoneal chemotherapy administration has emerged as a valuable alternative to traditional transvenous routes, showing promise for wider clinical adoption. The field of surgery has also evolved, with increasing exploration into the benefits and feasibility of laparoscopic methods over more invasive traditional surgeries, aiming for complete tumor removal but with reduced patient impact. The hereditary nature of ovarian cancer underscores the importance of genetic testing, which has become integral in tailoring treatment strategies, particularly in determining suitability for PARP inhibitors.The formation of the East Asian Gynecologic Oncology Trial Group (EAGOT) aims to optimize treatment across Japan, Korea, China, and Taiwan. The ovarian cancer committee of EAGOT shared the current policies, focusing on 5 topics: 1) strategies for maintenance therapy after initial surgery and chemotherapy, 2) drug regimens for platinum-sensitive and platinum-resistant recurrence, 3) intraperitoneal chemotherapy, 4) laparoscopic surgery as an alternative to laparotomy, and 5) current status of genetic testing (BRCA, HRD, and panel tests) for ovarian cancer and its prospects. EAGOT’s multi-national trials aim to harmonize these evolving treatment strategies, ensuring that the latest and most effective protocols are accessible across the region, thereby significantly impacting patient outcomes in East Asia.

Ovarian cancer, notable for its severe prognosis among gynecologic cancers, has seen substantial progress in treatment approaches recently. Enhanced protocols in chemotherapy and the introduction of poly (ADP-ribose) polymerase (PARP) inhibitors for maintenance therapy have markedly improved outcomes for patients with specific genetic profiles, such as those positive for BRCA mutations or exhibiting homologous recombination deficiency (HRD). Additionally, the method of intraperitoneal chemotherapy administration has emerged as a valuable alternative to traditional transvenous routes, showing promise for wider clinical adoption. The field of surgery has also evolved, with increasing exploration into the benefits and feasibility of laparoscopic methods over more invasive traditional surgeries, aiming for complete tumor removal but with reduced patient impact. The hereditary nature of ovarian cancer underscores the importance of genetic testing, which has become integral in tailoring treatment strategies, particularly in determining suitability for PARP inhibitors.The formation of the East Asian Gynecologic Oncology Trial Group (EAGOT) aims to optimize treatment across Japan, Korea, China, and Taiwan. The ovarian cancer committee of EAGOT shared the current policies, focusing on 5 topics: 1) strategies for maintenance therapy after initial surgery and chemotherapy, 2) drug regimens for platinum-sensitive and platinum-resistant recurrence, 3) intraperitoneal chemotherapy, 4) laparoscopic surgery as an alternative to laparotomy, and 5) current status of genetic testing (BRCA, HRD, and panel tests) for ovarian cancer and its prospects. EAGOT’s multi-national trials aim to harmonize these evolving treatment strategies, ensuring that the latest and most effective protocols are accessible across the region, thereby significantly impacting patient outcomes in East Asia.

Background/Aims: Cholestatic liver diseases including primary biliary cholangitis (PBC) are associated with active hepatic fibrogenesis, which ultimately progresses to cirrhosis. Activated hepatic stellate cells (HSCs) are the main fibrogenic effectors in response to cholangiocyte damage. JCAD regulates cell proliferation and malignant transformation in nonalcoholic steatoheaptitis-associated hepatocellular carcinoma (NASH-HCC). However, its participation in cholestatic fibrosis has not been explored yet. Methods: Serial sections of liver tissue of PBC patients were stained with immunofluorescence. Hepatic fibrosis was induced by bile duct ligation (BDL) in wild-type (WT), global JCAD knockout mice (JCAD-KO) and HSC-specific JCAD knockout mice (HSC-JCAD-KO), and evaluated by histopathology and biochemical tests. In situ-activated HSCs isolated from BDL mice were used to determine effects of JCAD on HSC activation. Results: In consistence with staining of liver sections from PBC patients, immunofluorescent staining revealed that JCAD expression was identified in smooth muscle α-actin (α-SMA)-positive fibroblast-like cells and was significantly up-regulated in WT mice with BDL. JCAD deficiency remarkably ameliorated BDL-induced hepatic injury and fibrosis, as documented by liver hydroxyproline content, when compared to WT mice with BDL. Histopathologically, collagen deposition was dramatically reduced in both JCAD-KO and HSC-JCAD-KO mice compared to WT mice, as visualized by Trichrome staining and semi-quantitative scores. Moreover, JCAD deprivation significantly attenuated in situ HSC activation and reduced expression of fibrotic genes after BDL. Conclusions JCAD deficiency effectively suppressed hepatic fibrosis induced by BDL in mice, and the underlying mechanisms are largely through suppressed Hippo-YAP signaling activity in HSCs.