ObjectiveTo clarify the expression of TRIM28 in non-M3 acute myeloid leukemia （AML） and its correlation with clinical indicators and prognosis， and to further explore the effect of TRIM28 expression levels on the proliferation and apoptosis of AML cells using small interfering RNA. MethodsThe GSE34577 dataset was analyzed using R software to compare TRIM28 expression between healthy controls and non-M3 acute myeloid leukemia （AML） patients. Clinical samples from non-M3 AML patients were collected， with TRIM28 expression levels measured using real-time quantitative PCR （qPCR）. The analysis focused on correlations between TRIM28 expression and various clinical indicators， treatment efficacy， and patient prognosis. Furthermore， small interfering RNA （siRNA） technology was employed to downregulate TRIM28 expression in human primary AML cells （HL60 cell line）. The effects on cell proliferation and apoptosis were then assessed through CCK-8 assays and flow cytometry， respectively. ResultsThe results showed that TRIM28 was up-regulated in non-M3 AML of both online database GSE34577 and clinical samples （P<0.000 1）， TRIM28 expression of new diagnosis group and relapsed refractory group was higher than iron deficiency anemia group （P<0.01）， and there was no significance between different French-American-British classification systems subtype. TRIM28 expression was higher in non-M3 AML patients with a poor genetic prognosis stratified as moderate than in the good prognosis group， and TRIM28 expression was associated with NPM1 combined with the FLT3-ITD mutation， positively correlated with age， bone marrow blast， peripheral blood blast and white blood cell， negatively correlated with hemoglobin. In addition， interference TRIM28 greatly inhibited cell proliferation and promoted cell apoptosis. ConclusionThis study reveals that TRIM28 is highly expressed in non-M3 AML and associated with prognosis， and plays a key role in the proliferation and apoptosis of AML cells， suggesting that TRIM28 may serve as a novel therapeutic target for non-M3 AML.

BACKGROUND:Muscle aging is closely related to various epigenetic changes,and exercise has a certain regulatory effect on these epigenetic changes.However,the specific mechanism is not fully understood. OBJECTIVE:To review the epigenetic mechanisms of skeletal muscle and how exercise can improve skeletal muscle aging and promote adaptive changes in muscle through these epigenetic mechanisms,aiming to provide a more comprehensive understanding of skeletal muscle aging and disease mechanisms. METHODS:During the period from June 1st to August 1st,2023,literature searches were conducted for relevant literature published from database inception to August 2023 in databases including Web of Science,PubMed,CNKI,WanFang,and VIP.The search terms used included"skeletal muscle,""muscle,""aging,""older adult,""aging,""exercise,""physical exercise,""epigenetic,"and"epigenetics"in Chinese as well as"skeletal muscle,muscle,aging,older adult,senescence,age,exercise,sports,physical activity,epigenetic,epigenetics"in English.Boolean logic operators were used to connect the search terms for retrieval,and corresponding strategies were developed.According to the predetermined inclusion and exclusion criteria,70 eligible articles were selected. RESULTS AND CONCLUSION:Epigenetics refers to the phenomenon where gene expression and function are regulated without changes in gene sequence,and epigenetic changes in skeletal muscle are an important field.The epigenetic mechanisms of skeletal muscle play an important role in muscle aging,mainly involving DNA methylation,histone modification,regulation of non-coding RNAs,chromatin remodeling,changes in mitochondrial function and expression changes of aging-related genes.Exercise significantly regulates the epigenetics of skeletal muscle,including promoting DNA methylation,muscle histone modification,regulating miRNA expression,and regulating lncRNA expression,regulating muscle factors(such as interleukin-6),regulating mitochondrial function(such as peroxisome proliferators-activated receptors γ co-activator 1α).Future studies are recommended for long-term,cross-diverse population-based exercise interventions;the application of multi-omics techniques such as proteomics and metabolomics;strengthening the understanding of epigenetic changes at the single-cell level;cross-species comparative studies as well as human clinical trials for the translation of animal model findings to humans;strategies for combining exercise and pharmacological interventions to assess their synergistic effects;and epigenetic studies of crosstalk interactions between skeletal muscle and different organs.

Objective: To explore effects of cumulative family risk in university students on individuals internalizing problems, to elucidate the mediating roles of perceived social support and self esteem in the relationship, so as to provide a basis for promoting university student s mental health. Methods: Using longitudinal design, 1 207 freshmen from a university in Tianjin were randomly selected and surveyed in November 2023 (T1) and November 2024 (T2). The instruments included the Cumulative Family Risk Scale, the Perceived Social Support Scale, the Self esteem Scale, and the College Student Mental Health Screening Scale. Structural equation modeling (SEM) was constructed, with Bootstrap method used to test mediating effects and to examine gender differences. Results: The results showed that cumulative family risk at T1 with internalizing problems at T1( r =0.30) and internalizing problems at T2 ( r =0.32) were significantly positively correlated (both P <0.01). Mediation analysis indicated that the independent mediating effect of perceived social support at T1，cumulative family risk at T1 and internalizing problems at T2 was 0.03 (95% CI =0.02-0.05), and the independent mediating effect of self esteem at T1 was 0.08 (95% CI = 0.06 -0.10) (both P <0.05). The chain mediating effect of perceived social support and self esteem at T1 was 0.02 (95% CI =0.02-0.03) ( P <0.05). Significant gender differences were observed in the path from cumulative family risk to self esteem ( β male =-0.24, β female =-0.35) and in the path from perceived social support to self esteem ( β male =0.41, β female =0.25) (all P <0.05). Conclusion Cumulative family risk reduces internalizing behaviors in university students via internal and external development resources, with gender specific mechanisms.

Objective:To investigate the accuracy and clinical utility of a newly designed acetabular bone defect classification system based on the ischial-gluteal pillar in assessing the severity of acetabular bone defects and guiding hip revision surgery.Methods:A retrospective analysis was conducted on 474 patients who underwent hip revision surgery for prosthetic loosening after total hip arthroplasty at our institution from January 2010 to December 2020, including 296 males and 178 females with a mean age of 70.4±8.9 years (range: 52-86 years). The accuracy of our classification system in guiding surgical procedures was evaluated by comparing preoperative defect classifications with intraoperative findings. Clinical outcomes were evaluated using preoperative and final follow-up Harris hip scores (HHS) and Oxford hip scores (OHS), as well as the incidence of complications.Results:Preoperative classifications included 143 Type I, 192 Type II (Type IIa: 86 cases, Type IIb: 59 cases, Type IIc: 47 cases), 93 Type III (Type IIIa: 54 cases, Type IIIb: 27 cases, Type IIIc: 12 cases), and 46 Type IV cases (Type IVa: 32 cases, Type IVb: 9 cases, Type IVc: 5 cases). Compared with intraoperative findings, classification accuracy was 99.3% for Type I (1 errors), 98.4% for Type II (3 errors), 97.8% for Type III (2 errors), and 97.8% for Type IV (1 misclassified as Type III). The mean follow-up was 5.8±4.4 years (range: 2-12 years). At final follow-up, mean HHS improved from 36.65±10.27 to 91.36±7.53, and mean OHS increased from 11.35±4.36 to 44.6±5.27 with significant difference ( P<0.001). Complications included one Type IV periprosthetic infection, one Type II hip dislocation, one Type I and two Type IV re-revisions (due to femoral loosening or graft resorption), one Type II and one Type III death unrelated to surgery, and one Type I postoperative thigh hematoma. No neurovascular injuries occurred. Conclusions:This novel 3D acetabular bone defect classification system, based on ischial-gluteal pillar integrity, provides accurate preoperative assessment and effectively guides surgical planning. Its application demonstrates favorable mid-term outcomes in hip revision surgery.

OBJECTIVE: To investigate the efficacy and safety of diagnostic-driven therapy for invasive fungal disease(IFD) in patients with myeloid hematologic malignancies. METHODS: A retrospective analysis was conducted on the clinical data of 91 patients with myeloid hematologic malignancies who received diagnostic-driven therapy for IFD at the Second Hospital of Anhui Medical University from January 1, 2020 to December 31, 2023. The patients were divided into two groups based on medication: 44 patients in the caspofungin group and 47 patients in the voriconazole group. The clinical efficacy and adverse reactions of the two groups were compared and analyzed. RESULTS: The overall response rates in the caspofungin and voriconazole groups were 67.4% and 60.0%, respectively. Among patients who transitioned to diagnostic-driven therapy following prophylactic or empirical treatment with triazole antifungal agents, the response rate of the caspofungin group was significantly higher than that of the voriconazole group (76.9% vs 35.3%, P <0.05). A total of 9 patients in both groups experienced adverse reactions, and no grade III or higher adverse reactions occurred. The incidence of grade I-II adverse reactions in the caspofungin group was lower than in the voriconazole group (2.3% vs 17.0%, P <0.05). CONCLUSION In patients with myeloid hematologic malignancies, caspofungin and voriconazole demonstrate comparable clinical efficacy in diagnostic-driven therapy for IFD, but caspofungin is associated with a lower incidence of adverse reactions. Caspofungin exhibits significant effectiveness when initiating diagnostic-driven therapy after prophylactic or empirical treatment with broad-spectrum triazole antifungal agents.
Humans ; Retrospective Studies ; Hematologic Neoplasms/complications* ; Antifungal Agents/therapeutic use* ; Voriconazole/therapeutic use* ; Caspofungin/therapeutic use* ; Invasive Fungal Infections/diagnosis* ; Male ; Female ; Mycoses/drug therapy* ; Middle Aged ; Treatment Outcome ; Aged ; Adult

Objective:To study the lipid metabolism and its relationship with iodine nutrition status in patients with papillary thyroid carcinoma (PTC) and benign thyroid nodules.Methods:A case-control study was conducted on patients with thyroid nodules initially diagnosed at Harbin Medical University Cancer Hospital from November 2015 to April 2019. Basic information, thyroid function indicators [thyroid stimulating hormone (TSH), free triiodothyronine (FT 3), free thyroxine (FT 4), thyroglobulin antibodies (TgAb), thyroid peroxidase antibodies (TPOAb)], and pathological diagnosis results were collected from all subjects. Fasting venous blood and morning urine samples were collected for serum iodine concentration (SIC), urine iodine concentration (UIC) and blood lipid indicators [total cholesterol (TC), triglyceride (TG), low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C), lipoprotein (a), apolipoprotein A1 (ApoA1), apolipoprotein B (ApoB), apolipoprotein E (ApoE), and non-esterified fatty acid (NEFA)] measurements. Results:A total of 1 090 subjects were included, including 907 PTC patients and 183 benign thyroid nodule patients. The UIC [ M ( Q1, Q3)] for the PTC group and benign thyroid nodule group were 143.36 (94.08, 227.94) and 146.28 (112.89, 236.07) μg/L, respectively, with statistically significant differences between the groups ( Z = 4.16, P = 0.042). Among PTC patients with different clinical pathological features, those with lymph node metastasis had higher FT 3 levels than those without lymph node metastasis ( t = 5.42, P = 0.021). The levels of TSH, TgAb, and TPOAb in patients with PTC combined with autoimmune thyroid disease (AITD) were higher than those without AITD ( Z = 11.87, 81.55, 475.96, P < 0.05). There was no statistically significant difference in the comparison of various blood lipid indicators ( P > 0.05). The correlation analysis showed that SIC in patients with thyroid nodules was positively correlated with FT 3, FT 4, ApoB, lipoprotein (a), NEFA, TG, LDL-C, and LDL-C/HDL-C ( P < 0.05). FT 3 was positively correlated with NEFA and LDL-C/HDL-C ( r = 0.12, 0.09, P < 0.05), and negatively correlated with ApoA1, TC, and HDL-C ( r = - 0.14, - 0.14, - 0.15, P < 0.001). FT 4 was positively correlated with NEFA ( r = 0.11, P < 0.001), and negatively correlated with TG ( r = - 0.10, P = 0.003). According to the iodine nutritional level, the ApoE level of PTC patients in the SIC < 45 μg/L group was higher than that in the 45 - 90 μg/L group ( P < 0.05). The levels of LDL-C and ApoB in patients with benign thyroid nodules in the SIC > 90 μg/L group were higher than those in the 45 - 90 μg/L group ( P < 0.05). The ApoE level of patients with benign thyroid nodules in the UIC < 100 μg/L group was significantly higher than that in the 100 - 299 and ≥300 μg/L groups ( P < 0.05). There was no statistically significant difference in thyroid function indicators of patients with PTC and benign thyroid nodules between different levels of SIC and UIC ( P > 0.05). Conclusions:Compared to benign thyroid nodules, PTC does not significantly affect patients' blood lipid levels. In patients with PTC and benign thyroid nodules, insufficient or excessive iodine nutrition can affect lipid metabolism.

To investigate the pathogenicity of Sheep-origin Proteus mirabilis and the immunity effect of its inactivated vaccine.In this study,autopsy were performed on sick and dead sheep with severe diarrhea,collected liver,spleen and other diseased organs.And identified the isolated strains by morphology,Gram staining microscopy,biochemical test,molecular biology and 16S rRNA se-quencing;Drug resistance and pathogenicity were studied by drug sensitivity test,pathogenicity test in mouse and pathological histological observation;The isolated strains were inactivated by formaldehyde and mixed with alum adjuvant containing aluminum hydroxide to prepare the inacti-vated vaccine;mice were immunized after safety testing to test antibodies,cytokines and evaluate the immunological effects.Results showed that the isolate was Gram-negative short bacillus with blunt rounded ends after purification staining.Combined with biochemical tests,PCR amplified fragments and 16S rRNA sequencing results showed that the strain was Proteus mirabilis;The re-sults of drug sensitivity test showed that the isolate was highly sensitive to four antibiotics,including amikacin and piperacillin(S),the rest of the strain was moderately or poorly sensitive,or even resistant;The isolate was highly sensitive to the four antibiotics,such as amikacin and pip-eracillin(S).The lethal concentration of the isolated strain was 1.6 × 105 CFU/mL and it could cause different degrees of congestion and bruising and inflammatory cell infiltration in the liver,spleen and other major organs;The formaldehyde inactivated vaccine did not cause adverse reac-tions in mice,and the serum levels of antibodies to IgG,IgG1 and IgG2a,and the levels of antibod-ies to IL-4 and IFN-γ were higher than that of the PBS group,and the vaccine immunoprotection rate was 90％in the attacking bacterial test.In the present experiment,Proteus mirabilis was suc-cessfully isolated from the organs of sick and dead sheep.The inactivated vaccine prepared by form-aldehyde inactivation method can mediate humoral immunity to play a preventive role against the infection of S.chimaera,which can provide a new method for the prevention of bacterial diseases in sheep breeding.

Spine fracture and dislocation are common traumatic spinal conditions that often require surgical intervention due to compromised spinal stability. Surgical approaches include anterior, posterior, and combined anterior-posterior spinal procedures. According to the specific surgical requirements, patients may be placed in the prone position or repositioned between prone and supine positions during surgery. Intraoperative repositioning has become an essential step in patient positioning. However, during repositioning, patients with spinal fracture and dislocation are at increased risk for complications such as hemodynamic instability, nerve injury, and pressure injuries to the skin and soft tissue. Notably, due to the instability of the spinal cord, even minor manipulations can further exacerbate the damage, potentially leading to severe outcomes like paraplegia. Although the current clinical guidelines provide instructive recommendations for standard position, there remains no specific protocols for intraoperative repositioning in patients with spine fracture and dislocation. With a concern for the lack of clinical studies on positioning techniques, risk prevention, and operational norms for special patients, no applicable guidelines or standards are available. A consensus was required to provide clinical reference, meet the requirements of surgical treatment, and minimize the safety risks of patients caused by improper placement of positions. Professional Committee of Operating Room Nursing of Shaanxi Nursing Association organized experts in nursing management and operating room nursing from major hospitals across China to formulate Expert consensus on intraoperative repositioning for patients with spinal fracture and dislocation ( version 2025). The consensus provides 11 recommendations covering pre-repositioning preparation, intraoperative maneuvers, and post-repositioning observation, aiming to provide references for clinical standardization of the intraoperative repositioning process and protection of patients′ safety.

Neutralizing antibodies have been designed to specifically target and bind to the receptor binding domain (RBD) of spike (S) protein to block severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus from attaching to angiotensin converting enzyme 2 (ACE2). This study reports a distinctive nanobody, designated as VHH21, that directly catalyzes the S-trimer into an irreversible transition state through postfusion conformational changes. Derived from camels immunized with multiple antigens, a set of nanobodies with high affinity for the S1 protein displays abilities to neutralize pseudovirion infections with a broad resistance to variants of concern of SARS-CoV-2, including SARS-CoV and BatRaTG13. Importantly, a super-resolution screening and analysis platform based on visual fluorescence probes was designed and applied to monitor single proteins and protein subunits. A spontaneously occurring dimeric form of VHH21 was obtained to rapidly destroy the S-trimer. Structural analysis via cryogenic electron microscopy revealed that VHH21 targets specific conserved epitopes on the S protein, distinct from the ACE2 binding site on the RBD, which destabilizes the fusion process. This research highlights the potential of VHH21 as an abzyme-like nanobody (nanoabzyme) possessing broad-spectrum binding capabilities and highly effective anti-viral properties and offers a promising strategy for combating coronavirus outbreaks.
Single-Domain Antibodies/immunology* ; Spike Glycoprotein, Coronavirus/metabolism* ; SARS-CoV-2/immunology* ; Animals ; Humans ; Antibodies, Neutralizing/immunology* ; Camelus ; COVID-19/immunology* ; Antibodies, Viral/immunology* ; Angiotensin-Converting Enzyme 2

Objective To explore the influence of heparin sodium on early recovery after lumbar surgery and the risk factors of deep vein thrombosis(DVT)of lower extremities,and build a prediction model for DVT after lumbar surgery based on the risk factors.Methods A total of 276 patients who underwent lumbar surgery and were treated with heparin sodium in The First Affiliated Hospital of Naval Medical University from January 2020 to January 2023 were selected as research objects.Activated partial thromboplastin time(APTT),prothrombin time(PT)and functional indexes of lumbar spine were recorded before and after treatment.DVT of lower extremities was detected by ultrasound during postoperative hospitalization,and then the patients were divided into DVT group and non-DVT group.The clinical data and laboratory indicators of all patients were collected.The risk factors of DVT after lumbar surgery were analyzed by logistic regression analysis.A postoperative DVT risk prediction model based on Logistic regression analysis was constructed and validated.Results APTT and PT after operation were higher than those before operation(P<0.05).The score of Oswestry Disability Index(ODI)3 months after surgery was lower than that before surgery(t=30.661,P<0.05).The incidence of DVT was 14.86%(41/276).Blood transfusion,bed rest≥5 d,proportion of general anesthesia,intraoperative blood loss,body mass index(BMI)and D-dimer level in the DVT group were higher than those in the non-DVT group(P<0.05).Logistic regression analysis showed that intraoperative blood loss,BMI,abnormal D-dimer level,intraoperative blood transfusion,and bed rest≥5 d were all risk factors for DVT after lumbar surgery(P<0.05).logit(P)=9.762+1.425×intraoperative blood loss+1.212×BMI+0.856×intraoperative blood transfusion+1.105×bed rest+1.671×D-dimer.Hosmer-Lemeshow test showed that the model had a high goodness of fit(χ2=4.025,P=0.473).The sensitivity,specificity and area under curve(AUC)of the constructed prediction model for postoperative DVT were 91.80%,70.40%and 0.836(95%CI:0.698-0.948),respectively.Conclusion Heparin sodium can improve blood circulation and lumbar function and prolong clotting time in patients with lumbar surgery.Intraoperative blood loss,BMI,abnormal D-dimer,intraoperative blood transfusion,and bed rest≥5 d are all risk factors for the occurrence of DVT after lumbar surgery.The prediction model based on the above risk factors has high predictive value for the occurrence of DVT after lumbar surgery.