OBJECTIVE: To compare the effects of double-channel core decompression (CD) combined with medullary cavity irrigation with those of simple CD on progression of collapse and clinical outcomes in non-traumatic osteonecrosis of the femoral head (ONFH). METHODS: A retrospective analysis was conducted on the clinical data of 19 patients (30 hips) with non-traumatic ONFH who underwent double-channel CD combined with medullary cavity irrigation and admitted between January 2024 and October 2024 (CD+irrigation group). According to a 1: 2 ratio, 54 patients (60 hips) who underwent simple CD and were matched in terms of age, gender, and body mass index (BMI) were included as the control (CD group). There was no significant difference in baseline data such as age, gender, BMI, affected side, ONFH type, preoperative Association Research Circulation Osseous (ARCO) stage, bone marrow edema stage, visual analogue scale (VAS) score for pain, and Harris score between the two groups ( P>0.05). The postoperative discharge time and occurrence of complications were recorded for both groups. The VAS scores before operation and at discharge after operation were compared, and the differences between pre- and post-operation (change values) were calculated for intergroup comparison. The Harris scores before operation and at discharge and 3 months after operation were also compared. During follow-up, X-ray film, CT, and MRI were performed for reexamination. The ARCO stage and bone marrow edema stage were evaluated at 3 months after operation and compared with those before operation to determine whether there was radiological progression or relief. RESULTS: All incisions in both groups healed by first intention after operation, with no infection, femoral neck fracture, or other operation-related complications. All patients were followed up, and the follow-up time of the CD+irrigation group was (146.8±27.7) days, and that of the CD group was (164.3±48.2) days; there was no significant difference between the two groups ( t=1.840, P=0.069). There was no significant difference in the length of hospital stay between the two groups ( P>0.05). At discharge after operation, the VAS score of the CD+irrigation group was significantly lower than that of the CD group ( P<0.05), and the change value was significantly higher than that of the CD group ( P<0.05). The Harris scores at discharge and 3 months after operation in the CD+irrigation group were significantly higher than those in the CD group ( P<0.05). The Harris score gradually increased with time, and the differences between different time points were significant ( P<0.05). Radiological reexamination showed that there was no significant difference in the ARCO stage and the incidence of radiological progression between the two groups at 3 months after operation ( P>0.05); however, the bone marrow edema stage and the degree of bone marrow edema relief in the CD+irrigation group were better than those in the CD group, with significant differences ( P<0.05). CONCLUSION Double-channel CD combined with medullary cavity irrigation can significantly alleviate hip joint pain and improve joint function in patients with non-traumatic ONFH, reduce the degree of bone marrow edema in the femoral head, and delay the progression of ONFH.
Humans ; Femur Head Necrosis/therapy* ; Retrospective Studies ; Male ; Female ; Decompression, Surgical/methods* ; Therapeutic Irrigation/methods* ; Adult ; Treatment Outcome ; Middle Aged ; Femur Head/surgery*

The ability of cells to sense and adapt to metabolic changes and environmental variations is essential for their functions. Recent advances in synthetic biology have uncovered increasing mechanisms through which cells detect changes in metabolism and environmental conditions, leading to broader applications. However, a systematic review on the regulation of cellular metabolism and environmental adaption is currently lacking. This article presents a comprehensive overview of this field from three perspectives. First, it introduces key transmembrane and sensor proteins involved in the cellular perception of metabolic and environmental changes. Next, it summarizes the adaptive regulation mechanisms that natural cells employ when confronted with intracellular and extracellular metabolic changes. Finally, the review explores the application scenarios based on cellular adaptive regulation in three aspects: dynamic control, rational metabolic engineering, and adaptive evolution and makes an outlook on the future development directions in this field. This review not only provides a comprehensive perspective on the mechanisms by which cells sense metabolic and environmental variations, but also lays a theoretical foundation for further innovations in the field of synthetic biology. With the continuous advancement of future technologies, a deeper understanding of cellular adaptive regulation mechanisms holds great potential to drive the development and application of novel biomanufacturing platforms.
Adaptation, Physiological ; Synthetic Biology ; Metabolic Engineering/methods* ; Environment ; Bacteria/genetics*

Although significant progress has been made in the development of novel targeted drugs for the treatment of acute myeloid leukemia(AML)in recent years,chemotherapy still remains the mainstay of treatment and the overall survival is poor in most patients.Here,we demonstrated the antileukemia activity of a novel small molecular compound NL101,which is formed through the modification on bendamustine with a suberanilohydroxamic acid(SAHA)radical.NL101 suppresses the proliferation of myeloid malignancy cells and primary AML cells.It induces DNA damage and caspase 3-mediated apoptosis.A genome-wide clustered regularly interspaced short palindromic repeats(CRISPR)library screen revealed that phosphatase and tensin homologous(PTEN)gene is critical for the regulation of cell survival upon NL101 treatment.The knockout or inhibition of PTEN significantly reduced NL101-induced apoptosis in AML and myelodysplastic syndrome(MDS)cells,accompanied by the activation of protein kinase B(AKT)signaling pathway.The inhibition of mammalian target of rapamycin(mTOR)by rapamycin enhanced the sensitivity of AML cells to NL101-induced cell death.These findings uncover PTEN protein expression as a major determinant of chemosensitivity to NL101 and provide a novel strategy to treat AML with the combination of NL101 and rapamycin.

OBJECTIVE To investigate the expression and prognosis of SDHB gene in pan-cancer by bioinformatics analysis,and to explore SDHB-related genes,potential pathways and immune cell infiltration in pheochromocytoma paraganglioma(PPGL).METHODS The expression of SDHB gene in pan-cancer and its relationship with survival prognosis were analyzed in The Cancer Genome Atlas(TCGA)and genotype-tissue expression(GTEx)databases.The expression changes of other genes affected by SDHB mutations,the enrichment analysis and signaling pathway analysis in PPGL patients were carried out by analyzing the TCGA database and the TARGET database.In addition,the relationship between SDHB expression and immune cell infiltration in PPGL patients was explored.RESULTS Compared with normal tissues,the expression of SDHB in 21 tumors was higher than that in normal tissues(P<0.01):BLCA,BRCA,CESC,COAD,DLBC,ESCA,GBM,HNSCC,LGG,LUAD,LUSC,OV,PAAD,PRAD,READ,SKCM,STAD,THCA,THYM,UCEC and UCS.It was expressed lower than normal in 7 other tumors(P<0.01),including ACC,CHOL,KICH,KIRC,KIRP,LAML and PPGL.The relationship between SDHB expression and survival prognosis was analyzed,and it was found that in STAD,KIRC,MESO,OS,and KIR,lower SDHB expression predicted poor prognosis,while higher expression predicted good prognosis.In UCEC,LGG,HNSCC,LAML,OSCC,and ACC,lower SDHB expression predicted a better prognosis,and similarly,higher expression predicted a poor prognosis.In correlation and enrichment analysis,the expression of SDHB was mainly related to neuroactive ligand-receptor interaction,Cushing's syndrome,cortisol synthesis and secretion,peptide receptor activity,G protein-coupled peptide receptor activity,neuropeptide receptor activity,intrinsic components of the synaptic membrane,components of the synaptic membrane,components of the postsynaptic specialized membrane,cyclic nucleotide-mediated signaling pathways,neuropeptide signaling pathways,glucocorticoid metabolism processes and other signaling pathways.In immune infiltration analysis,it was found that the immune cells with the highest infiltration in the SDHB lower expression group were pDC cells and TReg cells,suggesting that pDC cells and TReg cells may play a certain role in PPGL patients.CONCLUSION SDHB gene is abnormally expressed in a variety of tumors,and it has a certain correlation with the prognosis of tumors.In PPGL patients,the signaling pathways affected by SDHB and highly infiltrating immune cells provide new insights for future mechanistic studies and immunotherapy.

In recent years,the field of nucleic acid therapeutics has been flourishing,progressively establishing itself as the third generation of drug modalities following small molecules and antibody-based drugs.Artificial intelligence technology based on machine learning is advancing rapidly,which can significantly accelerate the development process of nucleic acid therapeutics.This review provides an overview of the foundational aspects of artificial intelligence algorithms,databases,and characterizations in the field of nucleic acid drug development.It elucidates the advances in the application of artificial intelligence in nucleic acid structural prediction,small nucleic acid drug design,and other research and development phases of nucleic acid therapeutics,aiming to offer some reference for the interdisciplinary development of artificial intelligence and nucleic acid drugs.

ObjectiveTo improve the response capabilities to disasters and prevent major epidemics， it is of practical use to study the capability evaluation system of the national emergency medical rescue team that combines theoretical training and practical exercises， to enhance the overall quality of the teams. MethodsFirst， a capability assessment system for the national emergency medical rescue team was constructed based on the INSARAG External Classification （IEC） standards of the national emergency medical rescue team. Then， based on the outcome based education （OBE） concept， we conducted innovative research on the curriculum design and exercise programs for team building and member training. Finally， an empirical analysis was conducted on the effectiveness of the evaluation system and training exercises based on the statistical analysis of the comprehensive quality evaluation of the Shanghai national emergency medical rescue team from 2020 to 2023， as well as the empirical analysis of the rescue exercise on the Cruise of spectrum. ResultsBased on the linear regression analysis of each core competency indicators， the five core competencies in the evaluation system， including rescue skills， medical and health knowledge， disaster coping ability， team cooperation ability， and mental resilience training， were positively correlated with the cumulative number of trainings （r=0.71， r=0.76， r=0.81， r=0.84， r=0.96，all P<0.05）， indicating that the training was effective and the course design was reasonable. Empirical cases showed that the three-dimensional rescue drill model had remarkable results in the actual combat application and ability improvement of team members. ConclusionThe training courses and drills designed based on the three-level assessment system are effective in improving the comprehensive capabilities of the national emergency medical rescue team.

Objective:To discuss the regulatory effect of berberine(BBR)on fatty acids in the human glioma T98G cells and its effect on the cell proliferation,migration,and invasion,and to clarify its potential mechanism.Methods:The T98G cells at logarithmic growth phase were divided into control group and different concentrations(25,50,and 100 mg·L-1)of BBR groups.Cell wound healing assay was used to detect the migration rates of the cells in various groups;Transwell chamber assay was used to detect the invasion rates of the cells in various groups.The T98G cells at logarithmic growth phase were divided into control group and 100 mg·L-1 BBR group,and Mass spectrometry was used to detect the fatty acid contents in the cells in two groups.The T98G cells at logarithmic growth phase were divided into control group and different concentrations(50,100,and 150 mg·L-1)of BBR groups;Western blotting method was used to detect the expression levels of phosphatidylinositol 3-kinase(PI3K),phosphorylated PI3K(p-PI3K),protein kinase B(AKT),phosphorylated AKT(p-AKT),sterol regulatory element-binding protein 1(SREBP-1),and fatty acid synthase(FASN)in the cells in various groups.The expression of FASN was suppressed by gene silencing technology,and the T98G cells at logarithmic growth phase were divided into control group,shFASN1 group,and shFASN2 group.Western blotting method was used to detect the expression levels of FASN protein in the cells in various groups;clone formation assay was used to detect the clone formation of the cells in various groups;cell wound healing assay was used to detect the migration rates of the cells in various groups.Results:Compared with control group,the migration rates and invasion rates of the cells in different concentrations of BBR groups were decreased in a concentration-dependent manner(P<0.01),and the fatty acid content in the cells in 100 mg·L-1 BBR group was significantly decreased(P<0.01).Compared with control group,the expression levels of p-PI3K,p-AKT,SREBP-1,and FASN proteins in the cells in 150 mg·L-1 BBR group were significantly decreased(P<0.05 or P<0.01),and the expression level of SREBP-1 protein in the cells in 100 and 150 mg·L-1 BBR groups were significantly decreased(P<0.01).After suppression of FASN expression,compared with control group,the expression levels of FASN protein in the cells in shFASN1 and shFASN2 groups were significantly decreased(P<0.01),and the expression level of FASN protein in the cells in shFASN2 group was lower than that in shFASN1 group(P<0.05);compared with control group,the numbers of clone formation and migration rates of the cells in shFASN1 and shFASN2 groups were significantly decreased(P<0.01),and the migration rate of the cells in shFASN2 group was significantly lower than that in shFASN1 group(P<0.05).Conclusion:BBR interferes with fatty acid synthesis in the glioma T98G cells by reducing the expression of the PI3K/AKT/SREBP-1/FASN pathway related proteins,and decrease their migration and invasion capabilities.

AIM: To evaluate the efficacy of phacoemulsification with intraocular lens implantation(PEI)combined with goniosynechialysis(GSL)and goniotomy(GT)under direct vision with gonioscope in the treatment of advanced primary angle-closure glaucoma(PACG)combined with cataract.METHODS: Retrospective case series study. A total of 62 patients(65 eyes)with advanced PACG combined with cataract who were treated in the Second Hospital of Anhui Medical University from December 1, 2021 to March 31, 2023 were enrolled, and they were divided into two groups according to different surgical methods. The control group(32 cases, 33 eyes)received PEI+GSL, whereas the observation group(30 cases, 32 eyes)received PEI+GSL+GT. The intraocular pressure(IOP), best corrected visual acuity(BCVA)and the number of anti-glaucoma medications of the two groups before surgery and at 1 d, 1 wk, 1, 3, and 6 mo after surgery were evaluated. In addition, the visual field, cup-to-disc ratio(C/D), angle open range, anterior chamber depth, and average thickness of retinal nerve fiber layer(RNFL)were evaluated before and 6 mo after surgery.RESULTS: There were significant differences in IOP and lowering range of average IOP at 6 mo between the PEI+GSL+GT group(16.68±2.65, 11.12±8.53 mmHg)and the PEI+GSL group(18.71±2.51, 8.32±4.17 mmHg; P<0.05), and there was no difference in the rate of IOP reduction(44.57%±21.79% and 35.20%±17.94%, P>0.05). The number of anti-glaucoma medications, BCVA, anterior chamber depth, and angle closure range were improved in the two groups at 6 mo after operation(all P<0.01). The number of medication reductions and the range of angle opening at 6 mo after surgery in the PEI+GSL+GT group were significantly higher than those in the PEI+GSL group(P<0.05), and there was no difference in the other indicators between the two groups(all P>0.05). There was no difference in the mean deviation of visual field, C/D and average thickness of RNFL between the two groups at 6 mo after operation compared with those before operation(all P>0.05). The complete surgery success rate of the PEI+GSL+GT group was 81%(26/32), and the conditional success rate was 94%(30/32); while those rates of the PEI+GSL group were 58%(19/33)and 76%(25/33), respectively. There were statistical significance in the success rate of surgery between the two groups(complete success rate χ2=4.275, P=0.039; conditional success rate χ2=4.040, P=0.044). No vision-threatening complications and another surgery occurred in either group.CONCLUSION: The study showed that for patients with advanced PACG with cataract, PEI+GSL+GT is more effective than PEI+GSL.