Elemene is widely recognized as an effective anti-cancer compound and is routinely administered in Chinese clinical settings for the management of several solid tumors, including non-small cell lung cancer (NSCLC). However, its detailed molecular mechanism has not been adequately demonstrated. In this research, it was demonstrated that elemene effectively curtailed NSCLC growth in the patient-derived xenograft (PDX) model. Mechanistically, employing high-throughput screening techniques and subsequent biochemical validations such as microscale thermophoresis (MST), microRNA-145-5p (miR-145-5p) was pinpointed as a critical target through which elemene exerts its anti-tumor effects. Interestingly, elemene serves as a binding stabilizer for miR-145-5p, demonstrating a strong binding affinity (dissociation constant (K _D) = 0.39 ± 0.17 μg/mL) and preventing its degradation both in vitro and in vivo, while not interfering with the synthesis of the primary microRNA transcripts (pri-miRNAs) and precursor miRNAs (pre-miRNAs). The stabilization of miR-145-5p by elemene resulted in an increased level of this miRNA, subsequently suppressing NSCLC progression through the miR-145-5p/mitogen-activated protein kinase kinase kinase 3 (MAP3K3)/nuclear factor kappaB (NF-κB) pathway. Our findings provide a new perspective on revealing the interaction patterns between clinical anti-tumor drugs and miRNAs.

Severe open tibiofibular fractures account for approximately 28.1% of all open fractures. Among them, Gustilo-Anderson type IIIB/C fractures present significant clinical challenges due to associated bone and soft tissue defects, high infection rates, and risk of amputation. Inadequate preoperative assessment may lead to suboptimal emergency surgical planning or intraoperative complications. Historically, external fixation was often preferred, but this approach has been associated with limitations such as restricted joint mobility, delayed bone union, joint stiffness, and disuse osteoporosis, resulting in poor functional recovery. With advancements of debridement techniques, standardization of antibiotic use, and popularization of early soft tissue coverage, early internal fixation has gained broader acceptance. Nevertheless, controversies persist regarding the choice of fixation method, timing of definitive fixation, use of reamed versus unreamed intramedullary nailing, and necessity of fibular fixation. To standardize the diagnosis and early management of severe open tibiofibular fractures, reduce complication rates, and improve functional recovery, the Society of Microsurgery of the Chinese Medical Association organized a panel of domestic experts to develop the Evidence-based guideline for the diagnosis and early fixation of severe open tibiofibular fractures ( version 2025), using evidence-based methodology. The guidelines provided 12 recommendations covering diagnostic and early fixation strategies of severe open tibiofibular fractures, aiming to provide clinicians with scientifically grounded and standardized guidance.

Elemene is widely recognized as an effective anti-cancer compound and is routinely administered in Chinese clinical settings for the management of several solid tumors,including non-small cell lung cancer(NSCLC).However,its detailed molecular mechanism has not been adequately demonstrated.In this research,it was demonstrated that elemene effectively curtailed NSCLC growth in the patient-derived xenograft(PDX)model.Mechanistically,employing high-throughput screening techniques and subsequent biochemical validations such as microscale thermophoresis(MST),microRNA-145-5p(miR-145-5p)was pinpointed as a critical target through which elemene exerts its anti-tumor effects.Inter-estingly,elemene serves as a binding stabilizer for miR-145-5p,demonstrating a strong binding affinity(dissociation constant(KD)=0.39±0.17 μg/mL)and preventing its degradation both in vitro and in vivo,while not interfering with the synthesis of the primary microRNA transcripts(pri-miRNAs)and precursor miRNAs(pre-miRNAs).The stabilization of miR-145-5p by elemene resulted in an increased level of this miRNA,subsequently suppressing NSCLC progression through the miR-145-5p/mitogen-activated pro-tein kinase kinase kinase 3(MAP3K3)/nuclear factor kappaB(NF-κB)pathway.Our findings provide a new perspective on revealing the interaction patterns between clinical anti-tumor drugs and miRNAs.

Severe open tibiofibular fractures account for approximately 28.1% of all open fractures. Among them, Gustilo-Anderson type IIIB/C fractures present significant clinical challenges due to associated bone and soft tissue defects, high infection rates, and risk of amputation. Inadequate preoperative assessment may lead to suboptimal emergency surgical planning or intraoperative complications. Historically, external fixation was often preferred, but this approach has been associated with limitations such as restricted joint mobility, delayed bone union, joint stiffness, and disuse osteoporosis, resulting in poor functional recovery. With advancements of debridement techniques, standardization of antibiotic use, and popularization of early soft tissue coverage, early internal fixation has gained broader acceptance. Nevertheless, controversies persist regarding the choice of fixation method, timing of definitive fixation, use of reamed versus unreamed intramedullary nailing, and necessity of fibular fixation. To standardize the diagnosis and early management of severe open tibiofibular fractures, reduce complication rates, and improve functional recovery, the Society of Microsurgery of the Chinese Medical Association organized a panel of domestic experts to develop the Evidence-based guideline for the diagnosis and early fixation of severe open tibiofibular fractures ( version 2025), using evidence-based methodology. The guidelines provided 12 recommendations covering diagnostic and early fixation strategies of severe open tibiofibular fractures, aiming to provide clinicians with scientifically grounded and standardized guidance.

BACKGROUND:Early diagnosis and treatment of intervertebral disc degeneration is particularly important.Pyroptosis of nucleus pulposus cells plays an important role in the early process of intervertebral disc degeneration,but the role of pyroptosis-related molecules of nucleus pulposus cells in early intervertebral disc degeneration and related molecular markers are still unclear. OBJECTIVE:To explore the diagnostic and therapeutic value of differentially expressed genes related to pyroptosis during intervertebral disc degeneration. METHODS:Public datasets of the GEO database were integrated for differential analysis,and intersected with 33 pyroptosis-related genes previously reported.Using Gene Ontology analysis and Kyoto Encyclopedia of Genes and Genomes,pathway enrichment analysis was performed in genes related to pyroptosis during intervertebral disc degeneration.Enrichment analysis of the intervertebral disc degeneration dataset was conducted using gene set enrichment analysis.To construct the immune cell spectrum in intervertebral disc degeneration samples,the correlation between the differentially expressed pyroptosis-related genes and immune cells was analyzed.Protein interaction networks were built.Screening of the Hub gene to identify key genes associated with intervertebral disc degeneration in protein interaction networks.The receiver operating characteristic curve of the differentially expressed pyroptosis-related genes was plotted,and the area under the curve was calculated.The clinical diagnostic value of target genes was explored.qRT-PCR was applied to verify the difference in the expression of pyroptosis-related genes between normal human nucleus pulposus cells and degenerated human nucleus pulposus cells with intervertebral discs. RESULTS AND CONCLUSION:(1)4426 differentially expressed genes associated with intervertebral disc degeneration were obtained,and 14 differentially expressed pyroptosis-related genes were obtained after the intersection.(2)Gene Ontology and Kyoto Encyclopedia of Genes and Genomes revealed important enrichment pathways,mainly related to inflammation,cell cycle,infection and NOD-like receptor pathway.Gene set enrichment analysis showed that pathways such as amino acid metabolism and P53 transcription regulation were significantly enriched in patients with intervertebral disc degeneration.Immune infiltration analysis suggested that the occurrence and development of intervertebral disc degeneration were closely related to immune cells.(3)A total of five Hub genes were screened,namely IL1-β,Caspase-1,AIM2,Caspase-5,and NLRC4.(4)Acquisition and identification of key biomarkers for intervertebral disc degeneration:After intersecting the two datasets of GEO with the pyroptosis-related gene,it was found that NLRP3 had significant expression differences,and the receiver operating characteristic curve showed that NLRP3 had clinical diagnostic significance.(5)qRT-PCR showed that the expression of Hub genes such as IL1-β,Caspase-5 and NLRC4 was significantly increased in the nucleus pulposus cells of intervertebral disc degeneration(P<0.05),and there was no difference in Caspase-1,AIM2 and NLRP3 expression(P>0.05).(6)It is suggested that cell pyroptosis plays an important mechanism in the occurrence and development of intervertebral disc degeneration,among which pyroptosis-related molecules NLRP3,IL1-β,Caspase-5 and NLRC4 have early diagnosis and treatment value.

Objective To establish an ultra-high performance liquid chromatography(UPLC)fingerprint and multi-index content determination method of Siraitiae fructus standard decoction.Methods 15 batches of Siraitiae fructus from different producing areas were collected,Siraitiae fructus standard decoction was prepared according to Technical Requirements for Quality Control and Standardization of Traditional Chinese Medicine Formula Granules,and the extract rate was calculated.UPLC was used to establish the fingerprint of 15 batches of Siraitiae fructus standard decoction and determine the contents of 11-O-mogroside V,kaempferitrin and mogroside V,which were the main effective components.The chemometrics analysis was used to evaluate the quality of Siraitiae fructus standard decoction and find possible quality markers.Results The extraction rate of 15 batches Siraitiae fructus standard decoction ranged from 24.79％to 34.95％.There were 16 common peaks in the fingerprint,and 4 components were identified.The Siraitiae fructus standard decoction was divided into 2 categories by chemometrics analysis,among which samples from Liuzhou,Guangxi were in one category and samples from Guilin,Guangxi were in another category.Seven differential markers were screened out under the condition of variable importance projection value,and the order was as follows:peak 8＞peak 7＞peak 5＞peak 12(kaempferitrin)＞peak 1＞peak 13＞peak 4.The contents of kaempferitrin,11-O-mogroside V and mogroside V in samples from Guilin,Guangxi were slightly higher than those in samples from Liuzhou,Guangxi.Conclusion The UPLC fingerprint and content determination method established in this study are feasible,which can provide a basis for the quality evaluation of Siraitiae fructus.The results of principal component analysis show that kaempferol is likely to become a quality marker of Siraitiae fructus.

Objective:To further improve the understanding of paroxysmal nocturnal hemoglobinuria (PNH), we retrospectively analyzed and summarized the clinical characteristics, treatment status, and survival status of patients with PNH in Zhejiang Province.Methods:This study included 289 patients with PNH who visited 20 hospitals in Zhejiang Province. Their clinical characteristics, comorbidity, laboratory test results, and medications were analyzed and summarized.Results:Among the 289 patients with PNH, 148 males and 141 females, with a median onset age of 45 (16-87) years and a peak onset age of 20-49 years (57.8% ). The median lactic dehydrogenase (LDH) level was 1 142 (604-1 925) U/L. Classified by type, 70.9% (166/234) were classical, 24.4% (57/234) were PNH/bone marrow failure (BMF), and 4.7% (11/234) were subclinical. The main clinical manifestations included fatigue or weakness (80.8%, 235/289), dizziness (73.4%, 212/289), darkened urine color (66.2%, 179/272), and jaundice (46.2%, 126/270). Common comorbidities were hemoglobinuria (58.7% ), renal dysfunction (17.6% ), and thrombosis (15.0% ). Moreover, 82.3% of the patients received glucocorticoid therapy, 70.9% required blood transfusion, 30.7% used immunosuppressive agents, 13.8% received anticoagulant therapy, and 6.3% received allogeneic hematopoietic stem cell transplantation. The 10-year overall survival (OS) rate was 84.4% (95% CI 78.0% -91.3% ) . Conclusion:Patients with PNH are more common in young and middle-aged people, with a similar incidence rate between men and women. Common clinical manifestations include fatigue, hemoglobinuria, jaundice, renal dysfunction, and recurrent thrombosis. The 10-year OS of this group is similar to reports from other centers in China.

A 14-year-old boy presented with coma and convulsion following a 3-day high fever of unknown origin was initially diagnosed with a central nervous system infection with uncertain pathogen. Direct microscopic examination of wet slides of cerebrospinal fluid cytology revealed active amoeboid trophozoites with different shapes. The amoeba trophozoite could be seen at high magnification after Wright′s-Giemsa staining. A diagnosis of primary amoebic meningoencephalitis was made according to the cellular morphology results of the cerebrospinal fluid, imaging data, and clinical symptoms. After high-throughput gene detection targeting the infection pathogen and specific PCR verification of amoeba species, it was confirmed that the infection was caused by Naegleria fowleri. Timely antiamoebic treatment and other related treatments were implemented, but the patient progressed to brain death after 50 days, leading to the discontinuation of treatment by the family.

Aim To reveal the mechanism of cross-species ischemic heart failure from the perspective of spatial and gene co-expression networks.Methods GSE210374 and GSE57338 high-throughput sequencing datas were re-trieved from the national center for biotechnology information gene expression database(NCBI-GEO),and R language soft-ware packages was used to analyze and screen differentially expressed genes(DEG)in different myocardial regions of myo-cardial infarction rats,as well as DEG of myocardial samples from patients with ischemic heart failure and healthy controls,and the regional expression of common genes was analyzed.Weighted gene co-expression network analysis(WGCNA)was used to screen the genes related to myocardial infarction and to carry out enrichment analysis,protein-protein interac-tion network(PPI)was constructed to screen core genes(HG).Results A total of 4 835 differentially expressed genes were screened out in myocardial infarction rats and normal controls,and 51 differentially expressed genes were screened out in ischemic heart failure patients and normal control samples,which revealed representative gene sets in the left ventricular myocardial infarction area(I area),border area(BZ area),and remote area(R area)after myocardial in-farction.Spatial expression analysis revealed that there were 20 co-expressed genes in each myocardial region,16 of which were expressed in all three regions,the number of genes specifically expressed in I,BZ and R regions were 2,0 and 2,respectively.Enrichment analysis showed that the functions of co-expressed genes were different in different region.The I and BZ regions were related to collagen fiber assembly,stress-induced cardiomyocyte hypertrophy,down-regulation of c-Jun amino terminal kinase(JNK signal)and cell proliferation,and complement signaling pathways;The I and R regions were enriched in the binding of Wnt and collagen;As a non-ischemic distal R region,the co-expressed genes were signifi-cantly enriched in the extracellular matrix for functions such as compressive resistance,cytolysis and inhibition of T cell proliferation.Furthermore,it was worth noting that the products of co-expressed genes in the three regions were mostly lo-cated in the extracellular space and extracellular matrix,suggesting that there may be active cellular secretion and interac-tion regulation.Further PPI analysis suggested that asporin(ASPN),osteoglycin(OGN)and collagentype ⅩⅥ alpha chain(COL14A1)gene might be the core genes of the mechanism mentioned above.Conclusions The common mechanism of ischemic heart failure in rats and human involves multiple signaling pathways such as complement and coagu-lation cascade signaling and Wnt;which may be closely related to cell apoptosis mediated by extracellular matrix and exo-somes;ASPN,OGN,and COL14A1 may be the core genes.This work is expected to provide spatial and pathway refer-ence for the selection of intervention targets and pathway in the transformation research related to ischemic heart failure.

Objective: Preliminary study on the clinical effect of preoperative ultrasound endoscopy combined with staining labeling technique to locate the actual boundary of esophageal and gastric cancer Methods: From September 1, 2015 to October 30, 2017, 18 patients with esophageal adenocarcinoma were enrolled in this study. The actual boundaries of esophageal and gastric-derived adenocarcinoma lesions were localized by endoscopic ultrasonography and staining. There were 10 males and 8 females. After completing the preoperative examination, 1-2 days before operation, endoscopic ultrasonography was used to locate the edge of the lesion. Two point injection of carbon nano suspension was used to mark the location of 1cm at the longest distance from the longitudinal axis of the tumor. According to the length of longitudinal axial staining, the thoracotomy was performed. Intraoperative proximal margin resection was used to send frozen pathology. According to the results of freezing, the operation was decided. After the operation, the specimens from the margin of the tumor were segmented into paraffin section, which was about 0.5cm in each segment, and the tumor cells were observed under the electron microscope at all levels of the paraffin sections. Results: The average time of preoperative endoscopic ultrasonography staining was(10.16±1.38) min, and the diameter of nano carbon diffusion was(1.43±0.41)cm. All patients in the operation could clearly see the nano carbon staining area under the naked eye. In the field, the average time of locating lesions was(1.27±0.53)min. 5 patients underwent thoracoabdominal surgery and 13 underwent abdominal surgery. The average length of the cut margin of the tumor was(4.74±1.12)cm, and the frozen pathology of the incision margin was negative, and no additional operation was performed. The routine pathology confirmed that all the specimens were negative. Conclusion The staining and labeling technique for adenocarcinoma of the esophagogastric junction under endoscopic ultrasonography can detect the tumor edge and the scope of invasion accurately. It provides guidance and guarantee for the smooth implementation of AEG precision surgery. It is a safe, rapid and effective positioning technique.