OBJECTIVE: To identify the underlying mechanism by which quercetin (Que) alleviates sepsis-related acute respiratory distress syndrome (ARDS). METHODS: In vivo, C57BL/6 mice were assigned to sham, cecal ligation and puncture (CLP), and CLP+Que (50 mg/kg) groups (n=15 per group) by using a random number table. The sepsisrelated ARDS mouse model was established using the CLP method. In vitro, the murine alveolar macrophages (MH-S) cells were classified into control, lipopolysaccharide (LPS), LPS+Que (10 μmol/L), and LPS+Que+acetylcysteine (NAC, 5 mmol/L) groups. The effect of Que on oxidative stress, inflammation, and apoptosis in mice lungs and MH-S cells was determined, and the mechanism with reactive oxygen species (ROS)/p38 mitogen-activated protein kinase (MAPK) pathway was also explored both in vivo and in vitro. RESULTS: Que alleviated lung injury in mice, as reflected by a reversal of pulmonary histopathologic changes as well as a reduction in lung wet/dry weight ratio and neutrophil infiltration (P<0.05 or P<0.01). Additionally, Que improved the survival rate and relieved gas exchange impairment in mice (P<0.01). Que treatment also remarkedly reduced malondialdehyde formation, superoxide dismutase and catalase depletion, and cell apoptosis both in vivo and in vitro (P<0.05 or P<0.01). Moreover, Que treatment diminished the release of inflammatory factors interleukin (IL)-1β, tumor necrosis factor-α, and IL-6 both in vivo and in vitro (P<0.05 or P<0.01). Mechanistic investigation clarifified that Que administration led to a decline in the phosphorylation of p38 MAPK in addition to the suppression of ROS expression (P<0.01). Furthermore, in LPS-induced MH-S cells, ROS inhibitor NAC further inhibited ROS/p38 MAPK pathway, as well as oxidative stress, inflammation, and cell apoptosis on the basis of Que treatment (P<0.05 or P<0.01). CONCLUSION Que was found to exert anti-oxidative, anti-inflammatory, and anti-apoptotic effects by suppressing the ROS/p38 MAPK pathway, thereby conferring protection for mice against sepsis-related ARDS.
Animals ; Sepsis/drug therapy* ; Quercetin/therapeutic use* ; Respiratory Distress Syndrome/enzymology* ; p38 Mitogen-Activated Protein Kinases/metabolism* ; Mice, Inbred C57BL ; Reactive Oxygen Species/metabolism* ; Apoptosis/drug effects* ; Male ; Oxidative Stress/drug effects* ; MAP Kinase Signaling System/drug effects* ; Lung/drug effects* ; Mice ; Lipopolysaccharides ; Macrophages, Alveolar/pathology* ; Inflammation/pathology* ; Protective Agents/therapeutic use*

The toad, known for its various medicinal properties including parotid gland secretion (toad venom), dried skin, and gallbladder (toad bile), holds considerable medicinal applications as a valuable traditional Chinese animal medicine. Currently, in-depth attentions have been paid to the chemical composition and pharmacological properties of toad venom and skin; however, a lesser number of detailed analyses were concentrated on the toad bile. This review provides an overview of the chemical constituents in the bile of the Bufo genus, with a special focus on the cholestane and bufadienolides, and highlights the progress in their biosynthetic pathway and pharmacological activities. The analysis uncovers a distinct category of unsaturated Δ²² or Δ²³-C₂₇/C₂₈ bile acids in the toad gallbladder, potentially acting as key intermediaries in forming C-17 α-pyrone of bufadienolides. Furthermore, the high presence of 3α-OH configured bufadienolides in toad bile, in contrast to the common 3β-OH configured found in toad venom or skin, indicates a possible link between their minimal toxicity and the toad's self-defensive or physiological control. This review provides scientific basis for the development and utilization of toad bile resources, and provides useful reference for the discovery of lead compounds, analysis of the biosynthetic pathway of bufadienolides, and research on toad physiology.

Objective:To conduct a retrospective study on the treatment outcomes of patients who underwent artificial temporomandibular joint (TMJ) replacement surgery and to evaluate the effectiveness of artificial TMJ treatment.Methods:This study selected 62 patients who received standard Biomet artificial TMJ treatment at Department of Orthognathic and TMJ Surgery, West China Hospital of Stomatology, Sichuan University from May 2010 to September 2023 as the study subjects. Among them, there were 15 male patients and 47 female patients. The average age was 33.5 years old(ranging from 18 to 67 years). This study statistically analyzed postoperative indicators, including maximum mouth opening, forward jaw movement, lateral movement, postoperative pain scores, and patient satisfaction.Results:This study included a total of 62 patients with 99 TMJ joints. No infections occurred postoperatively. The average follow-up period was 33.7 months (ranging from 7 to 170 months). At 6 months postoperatively, the mean mouth opening was (36.1±6.2) mm, lateral movement was (2.1±0.9) mm, and forward jaw movement was (1.0±0.9) mm. The pain visual analog scale score at 6 months postoperatively was (2.8±0.6), and patient satisfaction with the surgery was (8.8±1.1). Spiral CT scans conducted after surgery showed no joint dislocation or migration, and the artificial joint remained stable during the follow-up period.Conclusions:Artificial TMJ replacement is a valuable method for effectively restoring TMJ structure and essential functions related to mouth opening and chewing. It is worthy of promotion as a reconstructive approach for the temporomandibular joint

OBJECTIVE To analyze the narrow-band imaging(NBI)endoscopic characteristics of recurrent early glottic carcinoma patients after undergoing CO2 laser surgery with a suspend laryngoscopy.METHODS A retrospective study was conducted on patients with early-stage glottic carcinoma(Ⅰ-Ⅱ stage)who received CO2 laser surgery under supportive laryngoscopy at the Department of Otolaryngology Head and Neck Surgery,the Second Affiliated Hospital of Xi'an Jiao Tong University from January 2017 to December 2023.The medical history,treatment methods,laryngoscopy(including common white light endoscopy and NBI endoscopy),imaging examinations,and pathological results of patients with recurrent glottic carcinoma were collected at different time points including preoperation,postoperative 1 month,postoperative 3 months,and postoperative 6 months.The endoscopic characteristics of NBI in patients with recurrent glottic carcinoma were summarized.RESULTS First,among 18 patients with early-stage glottic cancer recurrence after CO2 laser,the diagnostic rate of NBI endoscopy for laryngeal cancer recurrence(88.89％,16/18)was significantly higher than that of common white light endoscopy(55.56％,10/18)(χ2=4.985,P=0.026).The intraepithelial papillary capillary loop(IPCL)was classified as a vertical vessel according to ELS in all relapsed patients.However,according to Ni classification,the IPCL of the 72.22％(13/18)were classified as type V,while the IPCL of 27.78％(5/18)showed suspicious abnormal neovascularization(punctate or dilated and curved).The proportion of patients with abnormal IPCL on the surgical surface at 1 month,3 months,and 6 months postoperatively was 0.00％,27.78％(5/18),and 61.11％(11/18),respectively,with statistically significant differences(χ2=16.164,P<0.001),which indicated that the longer the follow-up time for recurrent laryngeal cancer patients,the higher the proportion of patients with abnormal IPCL on the surface of the surgical area under NBI endoscopy.CONCLUSION For early glottic carcinoma after CO2 laser surgery with a suspend laryngoscopy,the appearance of suspicious new blood vessels with type Ⅴ IPCL and punctate or dilated curvature under NBI endoscopy may indicate early recurrence of laryngeal cancer.

OBJECTIVE To analyze the changes of temporary abnormal intraepithelial papillary capillary loop(IPCL)in the surgical area of early glottic laryngeal cancer after CO2 laser resection.METHODS A retrospective study was conducted on early-stage glottic carcinoma patients who visited the Department of Otolaryngology,Head and Neck Surgery at the Second Affiliated Hospital from January 2017 to November 2023.Patients who underwent CO2 laser surgery accepted electronic laryngoscopy examination at 1 month,3 months,and 6 months postoperatively(including white light endoscopy and narrowband imaging endoscopy(NBI),and their medical history,treatment methods,laryngoscopy images,imaging data,and pathological results before and after treatment were systematically collected.The changes in laryngoscopy characteristics at different follow-up times after surgery were analyzed.RESULTS This study included 55 patients with non recurrent early glottic carcinoma who underwent CO2 laser surgery.At 1 month,3 months,and 6 months after surgery,there were significant differences in the proportion of patients with pseudomembrane coverage(72.73%vs.25.45%vs.7.27%),granulation formation(60.00%vs.34.55%vs.1.82%),and abnormal IPCL(23.64%vs.7.27%vs.0.00%)on the surface of the surgical area(P<0.001),and abnormal IPCL(mainly type Va and Vb)can be observed under NBI endoscopy from 1 month to 3 months after surgery.Within 6 months after surgery,the pseudomembrane detachment,granulation regression,scar formation,and abnormal IPCL in the surgical area disappeared.CONCLUSION Early glottic carcinoma patients may experience temporary abnormal IPCL within 3 months after receiving CO2 laser resection,but the abnormal IPCL could disappear within 6 months after surgery for some patients.Therefore,close observation is necessary within 6 months after surgery and there is no need for urgent biopsy.

After implantation, complex and highly specialized molecular events render functionally distinct organ formation, whereas how the epigenome shapes organ-specific development remains to be fully elucidated. Here, nano-hmC-Seal, RNA bisulfite sequencing (RNA-BisSeq), and RNA sequencing (RNA-Seq) were performed, and the first multilayer landscapes of DNA 5-hydroxymethylcytosine (5hmC) and RNA 5-methylcytosine (m⁵C) epigenomes were obtained in the heart, kidney, liver, and lung of the human foetuses at 13-28 weeks with 123 samples in total. We identified 70,091 and 503 organ- and stage-specific differentially hydroxymethylated regions (DhMRs) and m⁵C-modified mRNAs, respectively. The key transcription factors (TFs), T-box transcription factor 20 (TBX20), paired box 8 (PAX8), krueppel-like factor 1 (KLF1), transcription factor 21 (TCF21), and CCAAT enhancer binding protein beta (CEBPB), specifically contribute to the formation of distinct organs at different stages. Additionally, 5hmC-enriched Alu elements may participate in the regulation of expression of TF-targeted genes. Our integrated studies reveal a putative essential link between DNA modification and RNA methylation, and illustrate the epigenetic maps during human foetal organogenesis, which provide a foundation for for an in-depth understanding of the epigenetic mechanisms underlying early development and birth defects.
Humans ; DNA Methylation ; RNA ; Epigenesis, Genetic ; DNA/genetics* ; Basic Helix-Loop-Helix Transcription Factors/genetics*

Objective: To explore the role and significance of pyroptosis in gas explosion-induced acute lung injury (ALI) in rats. Methods: In February 2018, 126 SPF male SD rats were selected and randomly divided into blank control group (18 rats) and experimental group (40 m, 80 m, 120 m, 160 m, 200 m and 240 m, 18 per group) . The experimental group carried out gas explosion in the roadway to build the ALI model, the control group did not carry out gas explosion, and other conditions were consistent with the experimental group. Respiratory function indexes such as respiratory frequency (f) , tidal volume (TV) , minute ventilation (MV) and airway stenosis index (Penh) were measured 24 hours after the explosion. 5 rats in each group were sacrificed after anesthesia, Hematoxylin-Eosin (HE) staining was used to observe the pathological morphology of lung tissue. Immunohistochemistry was used to detect the content of Caspase-1. Western blotting was used to detect the content of cell pyroptosis including nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) , Caspase-1, interleukin-1β (IL-1β) and interleukin-18 (IL-18) in lung tissue related protein expression. Results: The f and MV of rats in the experimental group were higher than those in the control group (P<0.05) . Except for the 40 m and 80 m groups, the TV of rats in the other experimental groups were higher than those in the control group (P<0.05) . Except for the 40 m group, the Penh of rats in the experimental groups were lower than those in the control group (P<0.05) . HE staining showed that the lung tissue of the experimental groups at different distance points showed obvious edema of the pulmonary interstitium and alveoli, a large number of red blood cells and inflammatory cells exuded in the alveolar space, thickening of the pulmonary interstitium, and increased lung injury score (P<0.05) . The results of immunohistochemistry showed that the positive expression of Caspase-1 in each experimental group was higher than that in the control group (P<0.05) . Western blotting results showed that the expression of pyroptosis-related proteins in each experimental group was higher than that in the control group (P<0.05) . Conclusion: Pyroptosis is involved in the pathophysiological process of gas explosion-induced ALI in rats.
Acute Lung Injury/pathology* ; Animals ; Explosions ; Lung/pathology* ; Male ; Pyroptosis ; Rats ; Rats, Sprague-Dawley

Objective To investigate the relation between vasculogenic mimicry (VM) and MIG-7 in osteosarcoma, as well as their roles in the prognosis, and to establish a model for predicting the prognosis of osteosarcoma. Methods VM was identified by CD31/PAS double-staining in 156 cases of AJCC stage Ⅱ extremity osteosarcoma. Tumor samples were also immunohistochemically stained for MIG-7 to determine whether it was associated with the occurrence of VM. Univariate and multivariate Cox regression analyses were used to identify prognostic factors and a prognostic nomogram for predicting 3- and 5-year OS and MFS was constructed. C-index and calibration curves were used to verify the predictive accuracy of the model. Results The MIG-7 expression in osteosarcoma tissues was associated with VM formation, but MIG-7 expression was not associated with gender, age, AJCCⅡA/ⅡB stage, tumor location, surgical type or histological response to pre-operative chemotherapy. Survival analysis showed that MIG-7 expression, VM and pre-operative chemotherapy were identified as three independent prognostic factors. The value of C-index in nomogram was greater than 0.7. The predicted calibration curve was similar to the standard curve. Conclusion MIG-7 accelerates the progression of osteosarcoma by promoting VM formation, and may also affect prognosis through other mechanisms. The nomogram could afford accurate prognosis prediction and individualized diagnosis and treatment for osteosarcoma patients.

Macroangiopathy is a complication of Type II Diabetes Mellitus (T2DM), which is mainly caused by fibrosis of blood vessels. Using T2DM rat models, we investigated whether the traditional Chinese medicine, Di-Dang Decoction (DDD), exhibited anti-fibrotic actions on great vessels. T2DM rats were randomly divided into non-intervention group, early-, middle-, late-stage DDD intervention groups and control groups, including pioglitazone group and aminoguanidine group. After administration of DDD to T2DM rats at different times, we detected the amount of extracellular matrix (ECM) deposition in the thoracic aorta. The results showed that early-stage intervention with DDD could effectively protect great vessels from ECM deposition. Considering that TGF-β1 is the master regulator of fibrosis, we further validated at the molecular level that, compared to middle- and late-stage intervention with DDD, early-stage intervention with DDD could significantly decrease the expression levels of factors related to the activated TGF-β1/Smad signalling pathway, as well as the expression levels of downstream effectors including CTGF, MMP and TIMP family proteins, which were directly involved in ECM remodelling. Therefore, early-stage intervention with DDD can reduce macrovascular fibrosis and prevent diabetic macroangiopathy.

Objective: To evaluate the use of ITS2 sequences as DNA barcode to identify the Zingiberaceae medicinal plants from E'mei area. Method: The genomic DNAs were extracted from 43 Zingiberaceae medicinal plant samples from Sichuan E'mei area. The ITS2 sequences of these samples were amplified and bidirectionally sequenced by PCR. 40 ITS2 sequences were downloaded from the GenBank,and then the interspecific and intraspecific genetic distances were calculated and analyzed by using MEGA 6.0 to construct Neighbor-joining (NJ) tree; TAXON DNA software was also used to analyze intraspecific and interspecific variations and barcoding gaps. The differences in secondary structure of the ITS2 sequences were predicted and compared. Result: The minimum interspecific distance in Zingiberaceae samples was greater than the maximum intra specific distance,with obvious barcoding gap. The NJ tree showed that the samples were clustered into five different branches,Alpinia,Curcuma,Globba,Hedychium,and Zingiber respectively,and further cluster into sub-branches. Significant differences were also present in the secondary structures of ITS2 between different samples. Conclusion: ITS2 sequences as DNA barcode can be used to conduct accurate and rapid identification of the Zingiberaceae plants and clearly figure out the phylogenetic relationship among them,providing guidance for the study of the distribution of medicinal plants of this genus,as well as theoretical basis for the quality control,medication safety and rational development of Zingiberaceae medicinal plants in E'mei area.