T-cell acute lymphoblastic leukemia (T-ALL) is a highly aggressive hematologic malignancy with a poor prognosis, despite advancements in treatment. Many patients struggle with relapse or refractory disease. Investigating the role of the super-enhancer (SE) regulated gene ubiquitin-specific protease 20 (USP20) in T-ALL could enhance targeted therapies and improve clinical outcomes. Analysis of histone H3 lysine 27 acetylation (H3K27ac) chromatin immunoprecipitation sequencing (ChIP-seq) data from six T-ALL cell lines and seven pediatric samples identified USP20 as an SE-regulated driver gene. Utilizing the Cancer Cell Line Encyclopedia (CCLE) and BloodSpot databases, it was found that USP20 is specifically highly expressed in T-ALL. Knocking down USP20 with short hairpin RNA (shRNA) increased apoptosis and inhibited proliferation in T-ALL cells. In vivo studies showed that USP20 knockdown reduced tumor growth and improved survival. The USP20 inhibitor GSK2643943A demonstrated similar anti-tumor effects. Mass spectrometry, RNA-Seq, and immunoprecipitation revealed that USP20 interacted with hypoxia-inducible factor 1 subunit alpha (HIF1A) and stabilized it by deubiquitination. Cleavage under targets and tagmentation (CUT&Tag) results indicated that USP20 co-localized with HIF1A, jointly modulating target genes in T-ALL. This study identifies USP20 as a therapeutic target in T-ALL and suggests GSK2643943A as a potential treatment strategy.

Astragalus membranaceus possesses the function of enhancing immunity, protecting the liver, diuretic, anti-aging, anti-stress, anti-hypertensive, and more extensive antibacterial effects. Polysaccharides, one kind of the major active ingredients of A. membranaceus, are considered to be responsible for their versatile use. Now, a systematic summary of research progress and prospects of polysaccharides from A. membranaceus polysaccharides (AMPs) is necessary to facilitate their further study and application. In this review, the optimal extraction methods, structural features, biological activities, and applications of AMPs were emphasized. The structure-activity relationships are also analyzed and elucidated. Solvent, ultrasonic, microwave, enzyme-assisted, ultra-high pressure, and combined methods have been used to extract AMPs. Among them, solvent extraction is the most commonly used method because it is simple and easy to operate, but the efficiency needs to be improved further. The ultra-high pressure method is the most efficient but has a low economic return. AMPs exhibited various bioactivities, including immunomodulation, antitumor, and antidiabete. The structure-activity relationships revealed that different structure configurations, chain conformations, and physical properties would have different bioactivities. However, the new method for purification of certain polysaccharides, detailed structure-activity relationships (SAR), mechanisms of bioactivities, and quality control of AMPs need to be extensively investigated.

ObjectiveTo investigate the trends and significant determinants of delayed HIV diagnosis （DHD） among newly reported HIV/AIDS cases in Xuhui District， Shanghai between 2018 and 2022. MethodsIn the newly reported HIV/AIDS cases， patients died within one year without accident， HIV/AIDS cases with CD₄ cell count <200 cells·μL^-1， and AIDS cases with a CD₄ cell count between 200 to 499 cells·μL^-1 were defined as delayed diagnosis. Univariate and multivariate logistic analysis were employed to explore the influencing factors of DHD. ResultsAmong the 862 newly reported HIV/AIDS cases， The DHD rate was 39.79% without statistically significant difference by year（χ²=4.508， P=0.342）. Patients with CD₄ cell count <200 cells·μL^-1 contributed the largest proportion of DHD. During 2018‒2022， the DHD rate declined among HIV/AIDS patients who were younger than 35 years old or 45‒65 years old， never married， original diagnosis from tertiary specialized hospitals. Patients who were 65 years or older， married or divorced， with heterosexual transmitted HIV/AIDS， and original diagnosis from other types of testing and tertiary metropolitan hospital， had sustainably higher DHD rates. The number of HIV screening and diagnosed from voluntary counseling and testing （VCT） decreased during the COVID-19 epidemic， while the DHD rate increased sharply. Multivariate logistic regression analysis suggested the DHD rates were higher among older age， other types of testing（OR=3.805， 95%CI： 2.260‒6.406）and pre-operative testing（OR=2.411， 95%CI： 1.424‒4.081）. Patients who received CD₄ test in 15 days had a higher DHD rate compared to the cases received CD₄ test exceeding 90 days （OR=0.336， 95%CI： 0.216‒0.522）. ConclusionThere is no significant decrease of delayed HIV diagnosis rate in Xuhui District in recent years， and the number of HIV tests has decreased in 2022. Monitoring of newly reported HIV/AIDS should be conducted continuously. Expansion of HIV antibody screening should be conducted in non-infectious departments and inpatient departments in healthcare institutions， particularly metropolitan hospitals. Assistance should be provided to clinicians and elderly patients for improving their ability to recognize and perceive the risk of HIV/AIDS， in order to enhance early diagnosis and subsequent treatment.

OBJECTIVE To investigate the effects of ligustilide on chemotherapy resistance of cervical cancer cells based on Hippo-Yes-associated protein （YAP） signaling pathway. METHODS Human cervical cancer cisplatin-resistant cells HeLa/DDP were divided into control group， cisplatin group （10 μmol/L cisplatin）， cisplatin+ligustilide low-， medium- and high-concentration groups （10 μmol/L cisplatin+25， 50， 100 μmol/L ligustilide）. The proliferation， apoptosis， migration and invasion of HeLa/DDP cells were all detected in each group. The mRNA expressions of YAP and transcriptional coactivator with PDZ binding motif （TAZ） as well as the protein expressions of YAP， TAZ， matrix metalloproteinase 2 （MMP2）， Ki67， cleaved-caspase-3 and caspase-3 were determined in HeLa/DDP cells. RESULTS Compared with control group， the inhibitory rate， apoptotic rate and cleaved- caspase-3/caspase-3 of cisplatin group were increased significantly； scratch healing rate， the number of invasive cells， the mRNA expressions of YAP and TAZ， and the protein expressions of YAP， TAZ， MMP2 and Ki67 were decreased significantly in cisplatin group （P＜0.05）. Compared with cisplatin group， the inhibitory rate of cell proliferation， apoptotic rate and cleaved-caspase-3/ caspase-3 were further increased in cisplatin+ligustilide low-， medium- and high-concentration groups， while scratch healing rate， the number of invasive cells， the mRNA expressions of YAP and TAZ， and the protein expressions of YAP， TAZ， MMP2 and Ki67 were further decreased， in a dose-dependent manner （P＜0.05）. CONCLUSIONS Ligustilide can increase the sensitivity of drug-resistant cervical cancer cells to cisplatin by inhibiting Hippo-YAP signaling pathway.

Non-alcoholic fatty liver disease is a common chronic liver disease in clinical practice. In recent years, with increasing social attention to the health of women and the elderly, the prevention and treatment of non-alcoholic fatty liver disease after menopause has increasingly become a research hotspot in metabolic diseases. This study explores the pathogenesis and treatment method of non-alcoholic fatty liver disease in postmenopausal women based on the theory of "deficient qi and stagnation" and combined with the physiological and pathological characteristics of postmenopausal women and the Western medicine understanding of non-alcoholic fatty liver disease. We believe that the pathogenesis of non-alcoholic fatty liver disease in postmenopausal women is rooted in the "deficient qi" caused by depletion of liver and kidney essence and blood. The imbalance between the physical and functional aspects of the liver due to this "deficient qi" is the primary factor, while the "stagnation" of phlegm and blood stasis is the manifestation. Furthermore, the "deficient qi" and "stagnation" reinforce each other, with the deficiency leading to stagnation and stagnation exacerbating the deficiency, thus accelerating the progression of the disease. The treatment approach should be one that combines nourishing deficiency and resolving stagnation, addressing both root cause and maifestations. Given the female characteristic of "the liver as the innate organ" and the post-menopausal physiological state of "gradual decline of kidney essence", it is important to focus on nourishing the liver and kidneys, nurturing the liver′s physical body while maintaining its function, and also promoting the circulation of qi, resolving phlegm, and invigorating blood circulation to remove blood stasis. This approach aims to reduce the accumulation of lipids in the liver, offering a new perspective and approach for the treatment of non-alcoholic fatty liver disease in post-menopausal women with traditional Chinese medicine.

Objective To comapre and analyze the differences and commonalities of expression profiles of serum exosomal microRNA between patients with thyroid nodules and healthy persons at different iodine levels,and then provide evidence for screening early diag-nostic markers of thyroid nodules at different iodine levels.Methods The peripheral blood samples from 10 patients with thyroid nod-ules and healthy volunteers at different iodine levels were collected.Their serum iodine levels were measured by the arsenic cerium cat-alytic spectrophotometry.Serum exosomal microRNA were extracted and the expression levels of microRNA were determined by the high-throughput sequencing technology.The differential target genes were predicted and further performed Gene ontology(GO)analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)analysis.Results Compared with healthy volunteers,there were 6 downreg-ulated miRNAs in the patients with thyroid nodules at different iodine levels,namely miR-324-5p,miR-6511b-3p,miR-9903,miR-550a-3p,miR-5001-3p,and miR-3688-3p.Differentially expressed exosomal microRNA could regulate the MAPK signaling path-way,PI3K-AKT signaling pathway,VEGF signaling pathway,and NF-κB signaling pathway.Conclusion Six differentially expressed microRNAs is identified,which may serve as biological markers for the early diagnosis of thyroid nodules at different iodine levels.

BACKGROUND:Photothermal therapy is a novel tumor treatment strategy that uses photothermal agents to transform light energy into heat energy to accomplish non-invasive tumor ablation.The rise of photothermal therapy and nanotechnology has provided a new perspective on breast cancer treatment.OBJECTIVE:To prepare a new type of near-infrared biomimetic nanoprobe that has been modified by breast cancer cell membrane,to investigate the effect of near-infrared fluorescence/ultrasound imaging in vitro,and to observe its targeting ability and photothermal therapy effect on homologous tumor cells in vitro.METHODS:Organic small molecule ITIC-4CI with A-D-A structure was used as photothermal agents;polylactic acid/glycolic acid copolymer as nanocarrier;4T1 cell membrane of mouse breast cancer cells as a surface modifier of nanoparticles;perfluorohexane(PFH)was loaded.A novel near-infrared biomimetic nanoprobe(4T1m/ITIC-4CI/PFH)was prepared by the double emulsion evaporation method and sonication method.The basic characterization of the nanoprobe and the homologous targeting ability were detected.The photothermal properties and photothermal stability of the probe were investigated,and the near-infrared fluorescence/ultrasound imaging effect of the probe under laser irradiation was observed.The CCK-8 assay and calcein/propidium iodide staining were used to assess the efficacy of photothermal therapy.RESULTS AND CONCLUSION:(1)The prepared 4T1m/ITIC-4CI/PFH nanoprobes had uniform size,high stability,and an average particle size of(92.7±2.3)nm.The probe's protein composition was identical to that of the 4T1 cell membrane.The nanoprobe's ability to target homologous 4T1 cells was validated by an in vitro cell uptake assay.(2)The nanoprobe had a red-shift absorption spectrum and tail emission extending to the near-infrared-Ⅱ,which emitted a bright near-infrared-Ⅱ fluorescence signal under laser irradiation.(3)After laser irradiation,the nanoprobe 4T1m/ITIC-4CI/PFH could be turned into microbubbles and enhanced ultrasound imaging.The results of CCK-8 assay and calcein/propidium iodide staining showed that the nanoprobe 4T1m/ITIC-4CI/PFH had an obvious photothermal killing effect on 4T1 cells.(4)The results show that the nanoprobe 4T1m/ITIC-4CI/PFH has the ability to target homologous tumors and enhance near-infrared-Ⅱ fluorescence imaging/ultrasound imaging and photothermal therapy effects.

Objective To compare the outcomes of transvaginal natural orifice transluminal endoscopic surgery(vNOTES)and laparoendoscopic single-site surgery(LESS)for total uterine excision in obese patients with benign uterine lesions,and to investigate the utility of vNOTES in this patient population.Methods A total of 100 obese patients(BMI>28.0 kg/m2)diagnosed with benign uterine lesions requiring total uterine and bilateral salpingectomy between January 2022 and January 2023 were included in this study.They were randomly assigned to two groups:the LESS group(n=51)and the vNOTES group(n=49).Patient demographics,surgical duration,intraoperative blood loss,changes in hemoglobin levels,pain scores,time to first flatus postoperatively,length of hospital stay,pelvic floor function,sexual quality of life,and postoperative complications were compared between the two groups.Results The two groups did not show any statistically significant differences in terms of blood loss,pre-and postoperative hemoglobin changes,pelvic floor function,sexual quality of life,or postoperative complications(P>0.05).However,the vNOTES group exhibited shorter surgical durations,time to first flatus postoperatively,and length of hospital stay compared to the LESS group(P<0.05).Additionally,the vNOTES group demonstrated lower intraoperative pain scores than the LESS group.(P<0.05).Conclusions In obese patients with benign uterine lesions,vNOTES total uterine excision surgery demonstrated shorter surgical durations and postoperative hospital stays,lower postoperative pain scores,and better adherence to the principles of en-hanced recovery after surgery(ERAS),indicating its potential for broader application.

Objective:To test and evaluate the reliability and clinical effectiveness of osteoporotic thoracolumbar fracture (OTLF) scoring and classification system.Methods:A multicenter retrospective case series study was conducted to analyze the clinical data of 530 OTLF patients admitted to 8 hospitals including Honghui Hospital Affiliated to Xi'an Jiaotong University from January 2021 to June 2022. There were 212 males and 318 females, aged 55-90 years [(72.6±10.8)years]. There were 4 patients with grade C and 18 with grade D according to American Spinal Injury Association (ASIA) classification. According to the osteoporotic thoracolumbar injury classification and severity (OTLICS) score, all patients had an OTLICS score over 4 points and required surgical treatment. Among them, 410 patients had acute symptomatic OTLF (ASOTLF), including 24 patients with type I, 159 type IIA, 47 type IIB, 31 type IIC, 136 type IIIA, 8 type IIIB, 2 type IV (absence of neurological symptoms) and 3 type IV (presence of neurological symptoms), and 120 patients had chronic symptomatic OTLF (CSOTLF), including 62 patients with type I, 21 type II, 17 type III, 3 type IV (reducible under general anesthesia), 9 type IV (not reducible under general anesthesia), 1 type V (reducible under general anesthesia), 5 type V (presence of neurological symptoms), and 2 type V (not reducible under general anesthesia). Surgical procedures included percutaneous vertebroplasty (PVP), positional repositioning plus PVP, percutaneous kyphoplasty (PKP), posterior open reduction combined with bone graft fusion and bone cement augmented screw internal fixation, posterior open reduction combined with decompression, bone graft fusion and bone cement augmented screw internal fixation, and posterior open reduction combined with osteotomy and orthopedics, bone graft fusion and bone cement augmented screw internal fixation. A weighted Kappa was used to test the interobserver and intraobserver reliability of the OTLICS score, the ASOTLF classification, and the CSOTLF classification. The visual analog scale (VAS), Oswestry disability index (ODI), ASIA classification were compared before, at 1 month after surgery and at the last follow-up. Incidence of postoperative complications was observed.Results:The percentage of mean interobserver agreement for OTLICS staging was 93.4%, with a mean confidence Kappa value of 0.86, and the percentage of mean intraobserver agreement was 93.0%, with a mean confidence kappa value of 0.86. The percentage of mean interobserver agreement for ASOTLF staging was 94.2%, with a mean confidence Kappa value of 0.84, and the percentage of mean intraobserver agreement was 92.5%, with a mean confidence Kappa value of 0.83. The percentage of mean interobserver agreement for CSOTLF subtyping was 91.9%, with a mean confidence Kappa value of 0.80, and the percentage of mean intraobserver agreement was 91.3%, with a mean confidence Kappa value of 0.81. All the patients were followed up for 6-12 months [(9.0±2.1)months]. The VAS and ODI scores were significantly lower in patients with ASOTLF and CSOTLF classifications at 1 month after surgery and at the last follow-up than those before surgery (all P<0.05). The VAS scores in patients with ASOTLF types IIA, IIB, IIC, IIIA, and IV were significantly lower at the last follow-up than that at 1 month after surgery; the ODI scores in patients with ASOTLF types I, IIA, IIB, IIIA, IIIB and IV were significantly lower at the last follow-up than those at 1 month after surgery. The VAS scores in patients with CSOTLF types II, III, IV, and V were significantly lower at the last follow-up than those at 1 month after surgery, and the ODI scores in patients with all CSOTLF types were significantly lower at the last follow-up than those at 1 month after surgery (all P<0.05). Two patients with ASIA grade C recovered to grade D, and the rest recovered to grade E at the last follow-up ( P<0.01). No major vessel or nerve injury or internal fixation failure was found during follow-up. There were 18 patients with cement leakage, none of whom showed relevant clinical symptoms. There were 35 patients with new vertebral fractures, all of whom recovered well after symptomatic treatment. Conclusions:The OTLICS score, ASOTLF classification and CSOTLF classification have a high degree of reliability. Application of stepwise treatment for patients with different levels of injury according to the scoring and classification system can reduce pain, promote recovery of the spinal function, and reduce complications, which is of some significance in guiding the selection of clinical treatment.

Objective:To construct an evaluation index system for the core competence of hospital specialist service operation assistants and provide reference for the evaluation of such competence.Methods:From January to March 2022, literature analysis and behavioral event interviews were used to initially establish a core competence evaluation index system of hospital specialist service operation assistants, based on the Donabedian model. Subsequently, the Delphi expert consultation method was applied to conduct correspondence consultation, inviting experts to evaluate the contents and importance of the index system, using analytic hierarchy process to determine the weights of the indexes at all levels.Results:Two rounds of expert consultation were carried out, and the valid recovery rate of the questionnaire was 100%. The familiarity coefficient of the second round of correspondence was 0.87, the basis of judgment coefficient was 0.90, and the authority coefficient was 0.89. The final evaluation index system for core competence of hospital specialist service operation assistant consisted of 3 first-level indexes, 13 second-level indexes and 81 third-level indexes. The weight of the first-level index structure index was 0.266, and the highest weight among the second-level indexes was the operational development ability (0.083), while the highest weight among the third-level indexes of operational development ability was the comprehensive coordination ability (0.193); The weight of the first-level index process index was 0.405, and the corresponding second-level and third-level indexes with the highest weight were department operation practice work (0.157) and reasonable resource allocation (0.303), respectively; The weight of the first-level index result index was 0.329, and the corresponding second-level and third-level indexes with the highest weight were the weight of medical quality and safety (0.103) and drug adverse reaction reporting rate (0.237), respectively.Conclusions:The evaluation index system constructed in this study proves scientific and reasonable in weight assignment, proving a reference for the management of the specialist service operation assistants.