Approximately 60% of colorectal cancer (CRC) patients exhibit TP53 mutations, which are strongly associated with tumor progression, chemotherapy resistance, and an unfavorable prognosis. However, targeting p53 has historically been challenging, and currently, there are no approved p53-based therapeutics for clinical use worldwide. In this study, we discovered that ubiquitin carboxyl terminal hydrolase L3 (UCHL3) plays a crucial role in high-level glycolysis, enhanced stem-like properties, and 5-fluorouracil (5-FU) chemoresistance in TP53-mutant CRC by exerting its deubiquitinating enzyme activity to stabilize α-enolase (ENO1) protein. Notably, we identified a newly Food and Drug Administration (FDA)-approved drug, pacritinib, that potently suppresses UCHL3 expression by blocking the janus kinase 2 (JAK2)-signal transducer and activator of transcription 3 (STAT3) pathway in TP53-mutant CRC. Furthermore, Pacritinib was demonstrated to effectively inhibit glycolysis and improve the sensitivity to 5-FU chemotherapy in TP53-mutant CRC. Our findings suggest that targeting the JAK2-STAT3-UCHL3-ENO1 axis is a promising strategy to suppress glycolysis and enhance the efficacy of 5-FU chemotherapy in TP53-mutant CRC. Pacritinib shows potential for clinical application in the treatment of TP53-mutant CRC.

Objective:To assess the levels and abnormal rates of trace elements and vitamins among older patients in Beijing Hospital, and to analyze the correlations between these measured indicators.Methods:This study selected 49 older individuals who underwent physical examinations at Beijing Hospital between May 2021 and March 2024.The participants were divided into two age groups: 60-79 years old(23 cases)and 80-100 years old(26 cases). Levels' differences of trace elements and vitamins between the two age groups were analyzed.Pearson correlation analysis was used to investigate the correlations among the tested indicators, and multivariate analysis was conducted using a generalized linear regression model.Results:Among the 49 older individuals, the overall abnormal rate for trace element test results was 8.16%(4 cases), with 2 cases of iron(Fe)deficiency(4.08%)and 2 cases of calcium(Ca)deficiency(4.08%). The overall abnormal rate for vitamin test results was 24.49%(12 cases), which included 5 cases of vitamin B2 deficiency(10.20%), 1 case of vitamin C deficiency(2.04%), and 6 cases of vitamin D deficiency(12.24%). Statistically significant differences were observed between the two age groups in zinc(Zn)and vitamin C levels( t=2.84, 2.83; P=0.007, 0.007). Pearson correlation analysis revealed correlations among 19 pairs of indicators.The top five correlations were between plumbum(Pb)and cadmium(Cd)( r=0.769, P<0.001), Fe and manganese(Mn)( r=0.685, P<0.001), Ca and magnesium(Mg)( r=0.677, P<0.001), vitamin B12 and vitamin C( r=0.455, P=0.001), and vitamin B9 and vitamin D( r=0.422, P=0.003), respectively.The results of the multivariate analysis indicated that, after adjusting for the effects of age group and gender, statistical differences in correlations remained among the remaining trace elements and vitamins, except for those between vitamin B1 and vitamin B12, vitamin B1 and vitamin C, and vitamin A and vitamin D (all P<0.05). Conclusions:The deficiency rates of trace elements and vitamins remain notably high among older patients in our hospital, underscoring the necessity for enhanced nutritional supplementation and regular monitoring of trace element and vitamin levels within this population.Furthermore, a correlation exists between trace elements and vitamins, which offers valuable insights for the diagnosis and treatment of related diseases.

Extracorporeal membrane oxygenation (ECMO) serves as an advanced life support technology and plays a critical role in treating critically ill patients with severe cardiopulmonary failure. However, the unique physiological and pathological changes during pregnancy present numerous challenges and special considerations for the application of ECMO in obstetrics. Given the current lack of unified guidelines specifically for obstetric ECMO, clinical practice often relies on adapting general ECMO guidelines in combination with obstetric-specific factors. This article systematically reviews the core principles of existing general ECMO guidelines, provides an in-depth analysis of the impact of gestational physiological and pathological characteristics on ECMO application, and discusses the particularities and necessary adaptations of obstetric ECMO in terms of indications, anticoagulation strategies, parameter adjustment, multidisciplinary collaboration, and emergency management. Furthermore, it proposes strategies suitable for domestic clinical practice. The article also addresses existing difficulties and limitations not covered by current guidelines and calls for the urgent development of specialized obstetric ECMO guidelines to provide clinicians with more standardized and safer decision-making support, ultimately improving outcomes for critically ill pregnant patients and newborns.

Objective:To analyze the impact of different intrauterine intervention methods and types of complications on fetal prognosis in cases of giant placental chorioangioma (CA), and determine the indications for various treatment methods by analyzing cases of adverse outcomes.Methods:Relevant articles were retrieved from China National Knowledge Infrastructure, VIP Database, Wanfang Database, and Yiigle using the keywords "placental chorioangioma" and "fetal edema" or "anemia" or "cardiomegaly" or "polyhydramnios," and from PubMed, Embase, and UpToDate databases using the keywords "placental chorionic angioma or chorioangioma" and "fetal edema" or "anemia" or "polyhydramnios" or "hyperdynamic circulation" up to June 30th 2023. The size of the angiomas, fetal complications, intrauterine intervention methods, gestational weeks at intervention, and pregnancy outcomes were analyzed. Fetal and neonatal deaths were defined as adverse outcomes. Statistical analysis was performed using an independent sample t-test, rank-sum test, or Chi-square test (continuity correction Chi-square test or Pearson Chi-square test). Results:(1) A total of 582 articles were retrieved, and 51 articles were finally included, comprising 65 cases. Based on the intrauterine intervention methods, these cases were divided into the symptomatic treatment group (17 cases) and the etiological treatment group (48 cases). There were no statistically significant differences between the two groups in the maximum diameter of the angiomas, the gestational weeks at intervention, or the gestational weeks at delivery. (2) The incidence of adverse outcomes was 3/17 in the symptomatic treatment group and 27.1% (13/48) in the etiological treatment group, with no statistically significant difference. In the etiological treatment group, the incidence of adverse outcomes in cases with fetal edema was 45.4% (10/22), which was significantly higher than the 11.5% (3/26) in cases without fetal edema, and the difference was statistically significant ( χ 2=6.94, P=0.008). (3) An analysis of 13 cases with adverse outcomes revealed that nine cases had highly vascularized chorioangiomas and/or blood supply vessels located close to the umbilical cord insertion point on the placenta, and nine were complicated by fetal edema. The incidence of adverse outcomes for fetoscopic laser coagulation/bipolar coagulation, radiofrequency or microwave ablation, bioglue embolization, anhydrous alcohol ablation, and microcoil embolization were 4/19, 3/4, 1/8, 2/9, and 3/6, respectively. Conclusions:Intrauterine treatment of CA should be individualized. Bioglue embolization may be the first-line treatment; Fetoscopic laser coagulation can be applied to cases where the blood supply vessels are small and superficial;Interstitial laser ablation and radiofrequency ablation can be used for branch-type CA when the main blood supply vessels are located within the hemangioma; Anhydrous alcohol ablation is contraindicated due to its risk of fetal circulation entry; Microcoil embolization has the risk of incomplete occlusion, which should be used with caution.

Objective To compare four different methods for extracting exosomes derived from human umbilical cord mesenchymal stem cells(HUCMSCs-Exos) and obtain a simple, efficient, and cost-effective method for isolating exosomes.Methods The(Human umbilical cord Mesenchymal stem cells,HUC-MSCs)were subcultured, observed for cell morphology under microscope, and detected for cell proliferation ability, specific surface antigen expression level and multidirectional differentiation potential. The hucMSCs-Exos were extracted from the culture supernatant of HUC-MSCs by four methods, ultracentrifugation, polyethylene glycol(PEG) precipitation, sucrose precipitation and Total Exosome Isolation kit. The exosomes were observed for the morphology by transmission electron microscope, measured for the concentration and particle size by nanoparticle tracking analysis(NTA), detected for the total protein concentration by BCA, and detected for the specific marker protein level by Western blot.Results The subcultured HUC-MSCs showed long spindle shape and vortex adherence growth under microscope with fast cell proliferation, highly expressed MSCs specific surface antigens CD73 and CD90,and extremely low expressed hematopoietic stem cell surface markers CD34 and CD45, which had the potential to differentiate into adipocytes and osteoblasts. The HUCMSCs-Exos were extracted by all the four methods, except kit method, the exosomes obtained by the other three methods all displayed a cup-shaped double-layer membrane structure with clear boundaries. The total protein concentration and particle concentration of exosomes isolated using the kit were significantly higher than those of the other three methods(F = 35. 18, each P < 0. 01). The exosomes extracted by the four methods all expressed specific marker proteins CD63 and CD81. Except the exosomes extracted by sucrose precipitation did not express CD9, the exosomes extracted by the other methods all expressed CD9.Conclusion The exosomes can be extracted by all the four methods, and the quality of exosomes extracted by ultracentrifugation is stable; the yield of exosomes extracted by the kit is higher, more time-saving and more convenient; the purity of exosomes extracted by PEG precipitation and sucrose precipitation is higher. According to different production requirements, the appropriate exosomes isolation techniques can be selected.

Objective To understand the current situation and influencing factors of work-related musculoskeletal disorders (WMSDs) in medical staff in Beijing City. Methods A total of 2 687 medical staff were selected as the research subjects using the multi-stage sampling method. The current situation of WMSDs and occupational stress, anxiety symptoms, depressive symptoms, and insomnia symptoms were investigated using the Musculoskeletal Disorders Questionnaire, the Core Occupational Stress Scale, the Generalized Anxiety Disorder Scale, the Patient Health Questionnaire Depression Scale, and the Self-Sleep Management Questionnaire. The Max-Min Hill-Climbing algorithm was used to construct a Bayesian network model to analyze the influencing factors and internal relationships of WMSDs and to conduct reasoning and prediction of the model. Results The prevalence of WMSDs among the research subjects was 88.9%. Binary logistic regression analysis was used to identify age, educational level, personal monthly income, anxiety symptoms, depressive symptoms, insomnia symptoms, prolonged forward-head desk work, and prolonged static posture work to construct the Bayesian network model. The model consisted of nine nodes and eleven directed edges. Prolonged static posture work, prolonged forward-head desk work, and anxiety symptoms were directly related to WMSDs. Age and educational level were indirectly related to WMSDs through their influence on prolonged forward-head desk work. Depression symptoms were indirectly associated with WMSDs through their influence on anxiety symptoms. The model's prediction accuracy was 90.5%. Conclusion The prevalence of WMSDs among medical staff in Beijing City is relatively high. Prolonged static posture work, prolonged forward-head desk work, and anxiety symptoms may directly increase the risk of developing WMSDs.

This paper aims to discuss the construction and promotion strategy of medical care capacity framework based on the core literacy of palliative care， combining domestic and foreign research and clinical status. The research results show that it is particularly important to construct a framework of medical care competence based on palliative care. The core competencies required for palliative care include the ability to comprehensively evaluate and formulate personalized programs， effective communication skills， interdisciplinary teamwork skills， and the ability to continuously learn and improve themselves. The quality of care can be further improved if the above abilities are incorporated into the framework of medical care ability based on palliative care. However， there are a series of problems in the process of constructing the framework of palliative medical care capacity， such as difficult implementation of policy support， poor professionalism of talent team， single and irregular service model， low social acceptance， and difficult interdisciplinary cooperation and resource integration. After a detailed analysis of the problems， this paper puts forward the countermeasures to construct the framework of caring ability literacy based on palliative care. Effective countermeasures such as increasing policy support， cultivating comprehensive talents， developing diversified palliative care models， improving social recognition， and strengthening interdisciplinary cooperation and resource integration can effectively improve the core literacy and professional ability of medical care personnel， and then promote the development and improvement of palliative care services. In-depth discussion of the above contents can provide scientific reference for building a care model and literacy framework with palliative care as the core.

Objective:To investigate the efficacy of preserving the urethral ridge during Holmium laser enucleation of the prostate（HoLEP）in preventing postoperative retrograde ejaculation and to evaluate its impact on sexual function.Methods:This prospective cohort study enrolled patients with benign prostatic hyperplasia（BPH）who underwent HoLEP at Xiamen Haicang Hospital（Haicang Hospital Affiliated to Xiamen Medical College）from November 2022 to June 2024. Inclusion criteria were as follows：diagnosis of BPH confirmed by color Doppler ultrasound；International Prostate Symptom Score（IPSS）> 7；maximum urinary flow rate（Q max）< 15 ml/s；prostate-specific antigen（PSA）< 4 ng/ml；and an active sexual life with intact antegrade ejaculation. Exclusion criteria included neurogenic bladder，active urinary tract infection（UTI），and other relevant conditions. Patients were grouped based on the operating surgeon's comprehensive judgment during surgery，considering the degree of prostatic median lobe hyperplasia（preserved if hyperplasia was mild，not preserved if severe）. The EP-HoLEP group underwent “tunnel technique” enucleation of the middle lobe hyperplasia with preservation of the urethral ridge，while the HoLEP group underwent conventional prostate enucleation. Primary outcomes included postoperative retrograde ejaculation rate，International Index of Erectile Function（IIEF），Ejaculation Projection Score（EPS），IPSS，Quality of Life Score（QOL），Q max，post-void residual urine volume（PVR），operative time，and postoperative complications. Univariate analysis was used to screen potential influencing factors，followed by multivariate logistic regression to identify independent predictors. Results:Seventy patients with BPH were enrolled，with 35 in each group. Baseline characteristics，including age［（69.97 ± 5.14）years vs.（72.34 ± 5.08）years］，body mass index（BMI）［（22.99 ± 1.41）kg/m2 vs.（23.16 ± 1.38）kg/m2］，prostate volume［47.4（31.9，59.4）ml vs. 44.2（34.9，61.7）ml］，PSA［4.0（1.9，8.2）ng/ml vs. 3.1（2.6，5.0）ng/ml］，hemoglobin［（130.09 ± 12.92）g/L vs.（125.69 ± 17.26）g/L］，IPSS［17（10，22）vs. 17（10，27）］，QOL［5（4，5）vs. 4（4，5）］，Q max［7.5（6.3，9.1）ml/s vs. 7.0（5.9，8.9）ml/s］and PVR［65（22，167）ml vs. 60（16，150）ml］showed no statistically significant differences between the two groups（ P > 0.05）. Operative time［65（55，76）min vs. 63（55，73）min］，postoperative 2-hour hemoglobin［（124.17 ± 14.89）g/L vs.（120.11 ± 15.44）g/L］，and postoperative hospital stay［（3.94 ± 1.89）days vs.（3.66 ± 1.53）days］were also comparable between the two groups（ P > 0.05）. No significant difference was observed in the decrease in IIEF score［1（0，2）vs. 2（0，6）， P = 0.203］. EPS at 3 months［2（1，3）vs. 1（0，2）， P < 0.001］and at 6 months［2（1，2）vs. 1（0，2）， P < 0.001］postoperatively were significantly higher in the EP-HoLEP group. The incidence of postoperative UTI did not differ significantly［5.7%（2/35）vs. 2.9%（1/35）， P = 1.00］. Two cases of urinary retention occurred after catheter removal in the EP-HoLEP group，while none occurred in the HoLEP group. No blood transfusions or urethral strictures were reported in either group. The incidence of retrograde ejaculation was significantly lower in the EP-HoLEP group［28.6%（10/35）vs. 68.6%（24/35）， P <0.001］. Multivariable logistic regression analysis showed that urethral ridge preservation was an independent protective factor for retrograde ejaculation after HoLEP（ OR = 0.159，95% CI 0.053 ? 0.476， P = 0.001）. Conclusions:Urethral ridge preservation during HoLEP is safe and feasible，significantly reduces retrograde ejaculation，and preserves ejaculatory function，though it offers limited erectile function preservation. This approach is suitable for middle-aged，young，or younger elderly patients who prioritize ejaculatory quality，and provides clinical evidence for surgical optimization.

Objective To investigate the effects and mechanisms of Huatan Quyu Decoction on learning and memory abilities in rats with vascular dementia(VD).Methods Totally 112 male SD rats were randomly selected with 16 rats as the sham-operation group,the remaining rats were used to prepare VD models by segmental ligation of the common carotid artery.The successfully modeled rats were randomly divided into model group,Huatan Quyu Decoction low-,medium-and high-dosage groups(6.1,12.1,24.2 g/kg),donepezil hydrochloride group(0.5 mg/kg)and combination group(Huatan Quyu Decoction 12.1 g/kg+donepezil hydrochloride 0.5 mg/kg),with 16 rats in each group.Each group was given the corresponding treatment measures for 4 weeks.The Morris water maze test was used to assess learning and memory abilities,neurological function was evaluated using Garcia score,HE staining was used to observe the morphology of the hippocampal tissue,ELISA was employed to detect the serum content of Aβ,immunohistochemistry was utilized to observe the β-catenin,LRP6 and GSK-3β protein expression in brain tissue.Results Compared with the sham-operation group,the escape latency of the model group rats was prolonged(P<0.01),the number of crossing platforms was reduced(P<0.01),and the neurological deficit score was decreased(P<0.01),the arrangement of hippocampal tissue cells was disorderly,and the tissue was severely damaged,the serum Aβ content increased(P<0.01),the expressions of β-catenin and LRP6 protein in brain tissue decreased,and the expression of GSK-3β protein increased(P<0.01).Compared with the model group,the escape latency of rats in each administration group was shortened,the number of crossing platforms increased,the neurological deficit score increased,the number of hippocampal cells was relatively more,the arrangement was more orderly,and the structure was relatively complete,the serum Aβ content decreased,the expressions of β-catenin and LRP6 proteins increased,and the expression of GSK-3β protein decreased.Among them,Huatan Quyu Decoction high-dosage group had a significantly better effect than Huatan Quyu Decoction low-and medium-dosage groups(P<0.01),and there was no statistical significance in various indicators compared with the donepezil hydrochloride group(P>0.05).Compared with the donepezil hydrochloride group,the combination group showed significant improvements in learning and memory abilities(P<0.01),the neurological deficit score significantly increased(P<0.01),the number of hippocampal cells significantly increased,arranged neatly,and structurally intact,the serum Aβ content significantly decreased(P<0.01),the expression of β-catenin and LRP6 proteins significantly increased,and the expression of GSK-3β protein significantly decreased(P<0.01).Conclusion Huatan Quyu Decoction can repair cognitive function in VD rats,improve learning and memory abilities,and alleviate VD symptoms by activating the Wnt/β-catenin signaling pathway to reduce serum Aβ content,decrease the apoptosis of nerve cells and alleviate the degree of pathological damage in hippocampal tissue.

Objective::To analyze fetal renal abnormality genetic features and the prenatal characteristics of the 17q12 microdeletion syndrome.Methods::This prospective cohort study examined prenatal ultrasound findings of renal abnormalities in pregnant women who underwent single nucleotide polymorphism (SNP) array or copy number variation sequencing (CNV-seq) testing on amniotic fluid or fetal tissue at Tianjin Central Obstetrics and Gynecology Hospital between January 2016 and August 2022. The study cohort comprised women with advanced maternal age, fetal ultrasound anomalies, high-risk non-invasive prenatal testing results, or suspected 17q12 microdeletion syndrome. Comprehensive clinical data, including maternal age, detailed ultrasound findings, and pregnancy outcomes, were systematically collected. SNP-array analysis was conducted using an Affymetrix CytoScan 750 K Array Chip to identify CNVs and loss of heterozygosity, while CNV-seq was performed on the Illumina HiSeq 2000 platform. Detected variants were classified according to the American College of Medical Genetics and Genomics guidelines. Statistical analyses were performed using SPSS version 27.0.Results::Abnormal renal development was identified in 141 patients, among whom 26 exhibited hyperechogenic kidneys (HCK). Of these, 12 cases were associated with 17q12 microdeletion syndrome, while the remaining 14 were linked to other chromosomal abnormalities. When excluding patients with HCK, those diagnosed with polycystic kidney disease demonstrated a higher prevalence of chromosomal abnormalities compared to those with multicystic dysplastic kidney and renal dysplasia. Although isolated conditions such as horseshoe kidney, hydronephrosis, ectopic kidney, and unilateral kidney typically presented with normal chromosomal findings, the incidence of chromosomal abnormalities increased when these conditions coexisted with other anomalies. A detailed analysis of the correlation between 17q12 microdeletion syndrome and HCK revealed that 12 out of the 14 patients diagnosed with 17q12 microdeletion syndrome exhibited HCK. Genetic testing confirmed the syndrome in seven patients, with five cases attributed to novel mutations and two cases resulting from inherited mutations.Conclusion::Fetal HCK was closely associated with the 17q12 microdeletion syndrome, and polycystic kidney disease showed a higher rate of chromosomal abnormalities. Chromosome test results were mostly normal in patients with other renal abnormalities, such as kidney dysplasia, horseshoe kidneys, hydronephrosis, kidney deficiency, and ectopic kidneys. Prenatal diagnosis is recommended, especially in cases of non-isolated fetal renal abnormalities. This study provides strong evidence supporting a link between fetal renal abnormalities and genetic syndromes.