[摘 要] 目的：探讨胰岛素样生长因子2 mRNA结合蛋白3（IGF2BP3）、尿苷二磷酸-葡萄糖醛酸脱羧酶1（UXS1）在肝细胞癌（HCC）中的表达特征、预后价值及两者协同作用的分子机制。方法：整合UALCAN、cBioPortal、ENCORI、TISCH2、GDSC等公共数据库的转录组数据，对IGF2BP3和UXS1进行表达、预后评估、功能富集及药物敏感性等分析。收集GEO数据库的单细胞RNA测序（scRNA-seq）数据，分析细胞通信、单细胞代谢评分，系统解析IGF2BP3-UXS1轴在HCC中的具体作用。结果：IGF2BP3、UXS1在HCC组织中均显著高表达，且高表达患者总生存期显著缩短（均P < 0.05）。采用CRISPP技术敲除IGF2BP3或UXS1后，多种HCC细胞的增殖能力受到明显抑制。scRNA-seq分析揭示了IGF2BP3、UXS1在肝细胞等细胞类型中的广泛表达分布，前者在细胞分化晚期上调，后者则在细胞分化早、中期高表达。IGF2BP3、UXS1高表达组均显著激活了MIF通路，同时IGF2BP3的高表达削弱了成纤维细胞的相互作用，而UXS1的高表达则增强了T细胞的信号转导功能。IGF2BP3与UXS1在表达相关性中存在显著的正相关（r = 0.432，P < 0.05）。沉默IGF2BP3结合位点会导致UXS1表达水平变化（F = 0.333）。功能富集分析提示，IGF2BP3与UXS1协同调控能量代谢、蛋白质翻译等生物学过程。在IGF2BP3或UXS1高表达的细胞亚群中，发现两者与多个糖代谢相关通路存在显著关联。IGF2BP3、UXS1高表达的患者对优普色替等药物表现出显著的敏感性，还对药物那维托克等表现出显著的耐药性。结论： IGF2BP3、UXS1在HCC中高表达，两者通过调控糖代谢重编程的协同作用促进HCC恶性生物学行为。

Chemotherapy is currently the mainstay of systemic management for triple-negative breast cancer (TNBC), but chemoresistance significantly impacts patient outcomes. Our research indicates that Doxorubicin (Dox)-resistant TNBC cells exhibit increased glycolysis and ATP generation compared to their parental cells, with this metabolic shift contributing to chemoresistance. We discovered that ALKBH3, an m¹A demethylase enzyme, is crucial in regulating the enhanced glycolysis in Dox-resistant TNBC cells. Knocking down ALKBH3 reduced ATP generation, glucose consumption, and lactate production, implicating its involvement in mediating glycolysis. Further investigation revealed that aldolase A (ALDOA), a key enzyme in glycolysis, is a downstream target of ALKBH3. ALKBH3 regulates ALDOA mRNA stability through m¹A demethylation at the 3'-untranslated region (3'UTR). This methylation negatively affects ALDOA mRNA stability by recruiting the YTHDF2/PAN2-PAN3 complex, leading to mRNA degradation. The ALKBH3/ALDOA axis promotes Dox resistance both in vitro and in vivo. Clinical analysis demonstrated that ALKBH3 and ALDOA are upregulated in breast cancer tissues, and higher expression of these proteins is associated with reduced overall survival in TNBC patients. Our study highlights the role of the ALKBH3/ALDOA axis in contributing to Dox resistance in TNBC cells through regulation of ALDOA mRNA stability and glycolysis.

ObjectiveTo analyze the evolutionary characteristics and genetic variations of the HA (hemagglutinin) and NA (neuraminidase) genes of influenza A(H1N1) viruses in Shanghai during 2024, to investigate their transmission patterns, and to evaluate their potential impact on vaccine effectiveness. MethodsFrom January to October 2024, throat swab specimens were collected from influenza like illness (ILI) patients at 4 hospitals in Shanghai. Real-time fluorescence ploymerase chain reaction (RT-PCR) was used for virus detection and isolation of H1N1 influenza viruses. Forty influenza A(H1N1) virus strains were sequenced using Illumina NovaSeq 6000 platform, followed by phylogenetic analyses, genetic distance analysis, and amino acid variation analyses of HA and NA genes. ResultsPhylogenetic tree of the HA and NA genes revealed that the 40 influenza A(H1N1) virus strains circulating in Shanghai in 2024 exhibited no significant geographic clustering, with a broad origin of strains and complex transmission chains. Genetic distance analyses demonstrated that the average intra-group genetic distances of HA and NA genes among the Shanghai strains were 0.005 1±0.000 6 and 0.004 6±0.000 6, respectively, which were comparable to or higher than those observed in global surveillance strains. Both HA and NA genes displayed frequent mutations. Compared to the 2023‒2024 and 2024‒2025 Northern Hemisphere A(H1N1) vaccine strains (WHO-recommended), the HA proteins of 40 Shanghai strains exhibited amino acid substitutions at positions 120, 137, 142, 169, 216, 223, 260, 277, 356 and 451, with critical mutations at positions 137 and 142 located within the Ca2 antigenic determinant. Furthermore, mutations in the NA protein were observed at positions 13, 50, 200, 257, 264, 339 and 382. ConclusionThe genetic background of the 2024 Shanghai influenza A(H1N1) virus strains is complex and diverse, and antigenic variation may affect vaccine effectiveness. Therefore, it is recommended to enhance genomic surveillance of influenza viruses, evaluate vaccine suitability, and implement more targeted prevention and control strategies against imported influenza viruses.

Objective To investigate the efficacy of varying doses of methylprednisolone(MP)on mice with acute exacerbations of chronic obstructive pulmonary disease(AECOPD)induced with influenza A virus(IAV).Methods Mouse model of COPD was established using LPS combined with smoking for 12 weeks,and then these COPD mice were treated with administration of 40 μL IAV via nasal drip to establish a AECOPD model.A total of 15 AECOPD mice were randomly divided into low-,medium-and high-dose MP groups,oseltamivir group and blank group.The body weight and survival time were monitored within 10 d after IAV infection.On days 1,3,and 5 post-treatment,lung function was assessed using whole-body plethysmography(WBP),inflammatory factors in bronchoalveolar lavage fluid(BALF)were quantified with ELISA,viral titers in BALF were determined using plaque assays,and colony-forming units were evaluated with blood agar plates.Immunofluorescence analysis:① Pulmonary immunofluorescence assay:Mice were randomly categorized into(n=4):LPS 1-day group,LPS 3-day group,and LPS+MP treatment group.All groups received an initial dose of LPS via atomization;subsequently,the LPS+MP treatment group received a single gavage dose of MP.Lung tissues were harvested from the 1-day LPS group on 1 d post-treatment,and from the 3-day LPS and LPS+MP groups on 3 d for immunofluorescence staining.② Cellular immunofluorescence assay:Mouse bone marrow neutrophils were classified into blank control(no intervention),LPS stimulation(LPS group),MP intervention with LPS stimulation(LPS+MP group),and MP intervention alone(MP group).The above cells were collected in 4 h after corresponding interventions for subsequent cellular immunofluorescence analysis.Results ①The medium-dose MP group demonstrated the most significant improvement in survival rate,weight recovery,and lung function when compared to other groups(P＜0.05).② Treatment of medium-dose MP obviously reduced the levels of IL-6 and neutrophil extracellular traps(NETs)(P＜0.05),while,elevated inflammatory factors and NETs were observed in the high-dose MP group on day 5 post-treatment.③ Notable decline in the lung injury score was found in the medium-dose MP group than the other groups(P＜0.05).④The high-dose MP group exhibited substantial bacterial proliferation and delayed viral clearance since day 5 after treatment.Conclusion Medium-dose MP shows best efficacy in treatment of IAV-induced AECOPD,and the dose neither delays viral clearance nor increases the risk of bacterial infection following viral infection.

Objective To investigate the status of population dynamics and distribution changes of Aedes aegypti in Guangdong Province.Methods Continuous monitoring was conducted from May 2018 to July 2024 in Wushi Town and Qishui Town,Leizhou City,Zhanjiang City,Guangdong Province.Additionally,a survey of the distribution of Ae.aegypti along the Leizhou Peninsula coast was carried out.Results The density of Ae.aegypti in Zhanjiang showed a gradual decline from 2018 to 2024.The last detection of adult Ae.aegypti in Wushi Town was in September 2021,and the last larva was found in October 2023.No Ae.aegypti was detected in Qishui Town during surveys from 2021 to 2024.A survey of 18 coastal villages in the Leizhou Peninsula revealed no detections of Ae.aegypti.Conclusions This study provides a basis for understanding the distribution and population density fluctuations of Ae.aegypti,assessing its invasion risk,and scientifically conducting relevant prevention and control efforts.

BACKGROUND:Several studies have found that the total flavonoids of rhizome drynariae can promote neovascularization in the induced membrane,improve the biological properties of the induced membrane,and accelerate bone remodeling in the induced membrane,but the related molecular mechanisms still need to be further explored. OBJECTIVE:To explore the effect of total flavonoids of rhizome drynariae on bone remodeling in rat femoral Masquelet-induced membrane model by regulating H-type blood vessels. METHODS:Thirty-six male Sprague-Dawley rats were stratified by body mass and then randomly divided into blank group,model group and traditional Chinese medicine group,with 12 rats in each group.A 4-mm femoral bone defect model was established in all the rats.Bone defects in the model group and traditional Chinese medicine group were filled with polymethylmethacrylate bone cement.At 6 weeks after modeling,the tail bone of the rats was implanted in the blank group,as well as in the other two groups after removal of bone cement.The traditional Chinese medicine group was given 157.5 mg/kg per day of total flavonoids of rhizome drynariae at 3 days after bone implantation,while the model and blank groups were given the same amount of saline by gavage until the 8th week after bone implantation.Bone graft samples were taken for relevant testing at 8 weeks after implantation. RESULTS AND CONCLUSION:X-ray films showed that in the blank group,the fracture line in the defect area was clear,and only a small amount of bone callus formed;in the model group,the bone defect area still existed,where discontinuous cortical bone was visible;in the traditional Chinese medicine group,the defect area was filled with newborn bone tissues,the bone marrow cavity and part of the cortical bone formed,and the fracture line disappeared.Micro-CT scans showed that the amount of new bone in the defect area was low in the blank group,the number of bone trabeculae in the defect area was significantly increased in the model group,and a large amount of new bone tissue was filled in the bone defect area in the traditional Chinese medicine group.Hematoxylin-eosin staining results showed that in the blank group,only a small amount of new bone formed in the defect area and the quality of osteogenesis was poor;in the model group,there was more new bone tissue in the defect area,but some fibrous connective tissues were interspersed within the bone tissue;and in the traditional Chinese medicine group,a large amount of new bone formed in the defect area and the quality of osteogenesis was the best.CD31/Emcn immunofluorescence double-labeling staining results showed that the number of H-type blood vessels in the newborn bone tissue in the bone defect area of the blank group was sparse and sparsely distributed;compared with the blank group,there were more H-type blood vessels in the bone tissue in the bone defect area of the model group,and the blood vessels were distributed in relatively regular strips;the number of H-type blood vessels in the bone defect area of the traditional Chinese medicine group was the highest and the blood vessels were densely distributed.To conclude,the total flavonoids of rhizoma drynariae can upregulate the expression of H-type blood vessels to enhance the angiogenic-osteogenic effect,improve the osteogenic efficiency of the rat femoral Masquelet induced membrane model,and promote bone remodeling.

Objective To explore the effect of a phased rehabilitation training programme to relieve shoulder dys-function in patients after neck dissection and to provide effective solutions for postoperative shoulder joint function recov-ery of patients.Methods This study has been reviewed and approved by the Ethics Committee,and informed consent has been obtained from patients.A phased rehabilitaiton training programme for the shoulder after neck dessection was developed through literature review and discussion,and 70 eligible patients from Hospital of Stomatology,Sun Yat-sen University from December 2020 to April 2021 were selected and randomly divided into the test group and control group(35 patients in each group).The control group underwent motor rehabilitation training from 6 weeks postoperative to 1 year after surgery,such as shoulder mobility and coordination training and small range of motion training of the neck,while the test group took part in a rehabilitation training program that included familiarization maneuver training,protective rehabilitation,exercise rehabilitation,and resistance training in the following four stages:preoperative,postop-erative general anesthesia and awake until the removal of stitches,the removal of stitches until 6 weeks after surgery,and 6 weeks after surgery until 1 year after surgery.The frequency of training in both groups was at least 3 days per week,and the length of each training session was 10-15 min.The intensity of exercise was 2-3 points on the Borg Conscious Ex-ercise Intensity Scale(i.e.,mild-to-moderate tachypnea or fatigue).The neck dissection injury index(NDII)was used to evaluate the quality of life related to shoulder joint function at four time points:preoperative,postoperative 3 months,postoperative 6 months,and postoperative 12 months.The higher the score,the better the quality of life.Results 28 cases in the test group and 32 cases in the control group completed a one-year follow-up.At 3 and 6 months postopera-tive,the NDII of the test group was significantly higher than that of the control group[3 months postoperative:test group(93.48±9.36)vs.control group(80.00±11.34)(P＜0.001),6 months postoperative:test group(98.21±4.76)vs.control group(90.70±9.12)(P＜0.001)];12 months after surgery,the NDII of the test group(97.23±4.88)was still higher than that of the control group(96.33±4.49),but the difference was not statistically significant(P=0.458).The difference in NDII scores among subjects at 3,6,and 12 months after surgery was statistically significant in each group(P＜0.001).Conclusion The application of the phased rehabilitation training method in neck dissection patients has a feasibility and could improve the quality of life of patients'shoulder joint function within 6 months after surgery.

Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.

Objective:To investigate the efficacy of our self-made distractor in assistance of percutaneous minimally invasive treatment of Sanders Ⅱ and Ⅲ calcaneal fractures.Method:A retrospective study was conducted to analyze the clinical data of 51 patients with calcaneal fracture who had been treated from March 2020 to August 2022 at Department of Orthopedic Trauma, Changsha Central Hospital Affiliated to University of South China. There were 42 males and 9 females with an age of (44.6±10.2) years. All the 34 Sanders type Ⅱ fractures and 17 Sanders type Ⅲ fractures were isolated unilateral ones which were treated by percutaneous reduction and fixation with percutaneous screws assissted by our self-made calcaneal distractor. All patients were evaluated both clinically and radiologically. The interval from injury to surgery, surgery duration, hospitalization period, fracture union, complications, reduction of the posterior inferior articular surface, the American Orthopaedic Foot & Ankle Society (AOFAS) ankle-hindfoot score and visual analog scale (VAS) pain score were recorded. The length, width, height, B?hler angle, and Gissane angle of the calcaneus were measured and compared between pre-surgery and the last follow-up.Results:All patients in this cohort were followed up after uneventfull surgery for 21 (18, 24) months. The interval from injury to surgery was 0 (0, 1) d, the surgery duration 38 (35, 40) min, and the hospitalization period 4 (3, 4) d. All the surgical incisions healed smoothly without any wound-related complications. All fractures got united by the 12-week postoperative assessment with normal alignment of the posterior foot and no varus or valgus. One patient developed symptoms of sural nerve injury after surgery, and one patient experienced a screw rupture after surgery. Evaluation of the posterior subtalar articular surfaces revealed an anatomic reduction rate of 66.7% (34/51), a near-anatomical reduction rate of 33.3% (17/51), and no cases of approximate reduction or failure in articular surface reduction. The last follow-up found no loss of reduction. At the last follow-up, the AOFAS ankle-hindfoot score was 91.3 (87.0, 98.0) points, giving 32 excellent, 17 good, and 2 fair cases, resulting in an excellent and good rate of 96.1%, and the VAS pain score 0 (0, 1) point. At the last follow-up, the width [34.0 (32.6, 34.9) mm], height [49.6 (47.1, 50.4) mm], B?hler angle [35.8 (34.0, 37.8)°], and Gissane angle [129.0 (124.2, 135.6)°] of the calcaneus were all significantly improved compared with the preoperative values [(41.0±2.1) mm, 39.3 (37.9, 40.2) mm, -5.7 (-20.4, 4.6)°, 94.5 (80.4, 104.0)°] ( P < 0.05). There was no statistically significant difference in the length of the calcaneus between pre-surgery and post-surgery ( P > 0.05). Conclusion:In the percutaneous minimally invasive treatment of Sanders Ⅱ and Ⅲ calcaneal fractures, use of our self-made calcaneal distractor has demonstrated favorable clinical outcomes, making the surgery minimally invasive and efficient.

Objective To investigate the clinical and imaging characteristics of myelin oligodendrocyte glycoprotein antibody-associated disease(MOGAD).Methods The clinical symptoms,MRI features,results of laboratory tests and clinical prognosis of 14 MOGAD patients who were hospitalized in our hospital from June 2016 to June 2022 were collected and retrospectively analyzed.Their clinical and imaging characteristics were summarized and discussed.Results Among the 14 enrolled patients,there were 10 males and 4 females,with a male to female ratio of 2.5∶1.Their age of first onset was＜18 years in 3 cases,18～45 years in 8 cases,and＞45 years in 3 cases.Optic neuritis(10/14,71.43％)was the most common clinical type,followed by encephalitis or meningoencephalitis(9/14,64.29％),brainstem encephalitis(5/14,35.71％)and myelitis(5/14,35.71％).Visual impairment(10/14,71.43％)was the most common clinical symptom,followed by headache in 8 cases(8/14,57.14％),fever in 6 cases(6/14,42.86％),dizziness in 6 cases(6/14,42.86％),parethesia in 5 cases(5/14,35.71％),and seizures,limb paralysis,sphincter dysfunction,ataxia,and vomit were all in 4 cases(4/14,28.57％).Four patients(4/14,28.57％)had a history of upper respiratory tract infection before MOGAD onset.There were 10 patients undergoing cerebrospinal fluid(CSF)test,and 8 of them had abnormal results,including 2 patients(2/10,20％)of increased pressure,8 patients(8/10,80％)of larger WBC count in CSF,and 5 patients(5/10,50％)of elevated total protein in CSF.MRI displayed multiple lesion involvement,and there were 7 cases(7/14,50.00％)in cortical/subcortical white matter,6 cases in brainstem(6/14,42.86％),5 cases in optic nerve(5/14,35.71％),4 cases in spinal cord(4/14,28.57％).The hippocampus,thalamus,basal ganglia,and paraventricular white matter were involved in 3 cases(3/14,21.43％),respectively,and the cerebellum and corpus callosum were in 2 cases(2/14,14.29％),respectively.MRI lesions demonstrated patchy hyperintensity on T2 WI and T2 FLAIR,with patchy,nodular and linear enhancement.Among the 10 patients undergoing visual evoked potential(VEP)test,abnormalities were detected in 9 cases(9/10,90％),and 8(8/10,80％)had bilateral visual pathway abnormalities.Eight patients(8/14,57.14％)experienced relapse and remission course.Both methylprednisolone pulse therapy and immunoglobulin modulation therapy were effective in the acute phase.Five patients with relapsed remission presented a significant reduction in recurrence after immunosuppressants.Conclusion MOGAD is manifested with various clinical features,with vision loss,headache,fever and dizziness more common.MRI lesions of MOGAD involve cerebral cortex,subcortical white matter,brainstem,and optic nerve,etc.Patchy hyperintesive signals are observed on T2WI and T2 FLAIR,and some lesions can be enhanced.Corticosteroid pulse therapy and immunoglobulin therapy show effective treatment in the acute phase,and immunosuppressants in the remission phase can reduce relapse.