Pancreatic cancer is a kind of highly malignant tumor with a low survival rate and poor prognosis. The effectiveness of gemcitabine as a first-line chemotherapy drug is limited; however, it can activate dendritic cells and improve antigen presentation which increase the sensitivity of tumor cell to immunotherapy. Although immunotherapy has made some advancements in cancer treatment, the therapeutic benefit of programmed cell death receptor 1/programmed death receptor-ligand 1 (PD-1/PD-L1) blockade therapy remains relatively low. The chemokine C-X-C chemokine ligand 12 (CXCL12) contributes to an immunosuppressive tumor microenvironment by recruiting immunosuppressive cells. The receptor C-X-C motif chemokine receptor 4 (CXCR4), highly expressed in various tumors including pancreatic cancer, plays a crucial role in tumor development and progression. In this study, the anti-tumor immune response of human peripheral blood mononuclear cell (hPBMC) was enhanced using the combination of BsNb PX4 (anti-PD-L1&CXCR4 bispecific nanobody) and gemcitabine. In a co-culture system of gemcitabine-pretreated hPBMCs with tumor cells, the BsNb PX4 synergized gemcitabine to improve the cytotoxic activity of hPBMCs against tumor cells. Flow cytometry analysis confirmed increased ratio of CD8⁺ to CD4⁺ T cells in combination treatment. In NOD/SCID mice bearing pancreatic cancer, the combination treatment exhibited more infiltration of CD8⁺ T cells into tumor tissues, contributing to an effective anti-tumor response. This study presents potential new therapies for the treatment of pancreatic cancer. Ethical approval was obtained for collection of hPBMC samples from the Local Ethics Committee of Shanghai Jiao Tong University. All animal experiments were approved by the Animal Ethic Committee of Shanghai Jiao Tong University (authorizing number: A2024246).

This paper systematically summarizes the practical experience of the 2025 Dingri earthquake emergency medical rescue in Tibet. It analyzes the requirements for earthquake medical rescue under conditions of high-altitude hypoxia, low temperature, and low air pressure. The paper provides a detailed discussion on the strategic layout of earthquake medical rescue at the national level, local government level, and through social participation. It covers the construction of rescue organizational systems, technical systems, material support systems, and information systems. The importance of building rescue teams is emphasized. In high-altitude and cold conditions, rapid response, scientific decision-making, and multi-party collaboration are identified as key elements to enhance rescue efficiency. By optimizing rescue organizational structures, strengthening the development of new equipment, and promoting telemedicine technologies, the precision and effectiveness of medical rescue can be significantly improved, providing important references for future similar disaster rescues.

OBJECTIVE: To compare the effectiveness of single-stage vascularized lymph node transfer (VLNT) combined with lymphaticovenular anastomosis (LVA) and liposuction (LS) (3L) versus LVA combined with LS (2L) for the treatment of moderate-to-late stage upper limb lymphedema following breast cancer surgery. METHODS: A retrospective analysis was conducted on the clinical data of 16 patients with moderate-to-late stage upper limb lymphedema after breast cancer surgery, treated between June 2022 and June 2024, who met the selection criteria. Patients were divided into 3L group (n=7) and 2L group (n=9) based on the surgical approach. There was no significant difference (P>0.05) in baseline data between the groups, including age, body mass index, duration of edema, volume of liposuction, International Society of Lymphology (ISL) stage, preoperative affected limb volume, preoperative circumferences of the affected limb at 12 levels (from 4 cm distal to the wrist to 42 cm proximal to the wrist), preoperative Lymphoedema Quality of Life (LYMQoL) score, and frequency of cellulitis episodes. The 2L group underwent LS on the upper arm and proximal forearm and LVA on the middle and distal forearm. The 3L group received additional VLNT in the axilla, with the groin serving as the donor site. Outcomes were assessed included the change in affected limb volume at 12 months postoperatively, and comparisons of limb circumferences, LYMQoL score, and frequency of cellulitis episodes between preoperative and 12-month postoperative. Ultrasound evaluation was performed at 12 months in the 3L group to assess lymph node viability. RESULTS: Both groups were followed up 12-20 months, with an average of 15.13 months. There was no significant difference in the follow-up time between the groups (t=-1.115, P=0.284). All surgical incisions healed by first intention. No adverse events, such as flap infection or necrosis, occurred in the 3L group. At 12 months after operation, ultrasound confirmed good viability of the transferred lymph nodes in the 3L group. Palpation revealed significant improvement in skin fibrosis and improved skin softness in both groups. Affected limb volume significantly decreased in both groups postoperatively (P<0.05). The reduction in limb volume significantly greater in the 3L group compared to the 2L group (P<0.05). Circumferences at all 12 measured levels significantly decreased in both groups compared to preoperative values (P<0.05). The reduction in circumference at all 12 levels was better in the 3L group than in the 2L group, with significant differences observed at 7 levels (8, 12, 16, 30, 34, 38, and 42 cm) proximal to the wrist (P<0.05). Both groups showed significant improvement in the frequency of cellulitis episodes and LYMQoL scores postoperatively (P<0.05). While the improvement in LYMQoL scores at 12 months did not differ significantly between groups (P>0.05), the reduction in cellulitis episodes was significantly greater in the 3L group compared to the 2L group (P<0.05). CONCLUSION The combination of VLNT+LVA+LS provides more durable and comprehensive outcomes for moderate-to-late stage upper limb lymphedema after breast cancer surgery compared to LVA+LS, offering an improved therapeutic solution for patients.
Humans ; Female ; Lipectomy/methods* ; Retrospective Studies ; Anastomosis, Surgical/methods* ; Lymphedema/etiology* ; Middle Aged ; Upper Extremity/surgery* ; Breast Neoplasms/surgery* ; Lymph Nodes/blood supply* ; Adult ; Lymphatic Vessels/surgery* ; Iliac Artery/surgery* ; Postoperative Complications/surgery* ; Perforator Flap/blood supply* ; Treatment Outcome ; Mastectomy/adverse effects* ; Quality of Life ; Aged

OBJECTIVE: To investigate the clinical characteristics, treatment and prognosis of adult AML patients with NUP98::HOXA9 fusion gene. METHODS: From May 2017 to October 2023， among 2 113 AML patients who visited the Hematology Department of our hospital, patients with NUP98 rearrangements were screened. The clinical characteristics, chromosome karyotypes, immunophenotypes, gene mutations, treatment efficacy and prognosis of the patients with NUP98::HOXA9 positive were analyzed. RESULTS: Among the 2 113 AML patients, there were 18 cases with NUP98 rearrangement, including 14 NUP98::HOXA9 positive cases, with a detection rate of 0.66% (14/2 113). The median age of the NUP98::HOXA9 positive patients was 42.5 (23-64) years old. The most common chromosome karyotype was t(7; 11)(p15; p15). The immunophenotypes of all patients expressed CD13, CD33, CD117 and CD38, and most patients expressed CD34 and cMPO, while only a few expressed HLA-DR. Second-generation sequencing (NGS) was performed to detect genetic mutations associated with leukemia in all 14 patients, and the genes exhibiting a high frequency of mutation were WT1 (10/14), TET2 (7/14), and FLT3-ITD (6/14). Additionally, mutations were also observed in KRAS/NRAS, IDH1, and KIT. Of the 13 patients who received treatment, 9 achieved complete remission (CR), and all 3 patients who received azacytidine(AZA)+ venetoclax (VEN) regimen achieved CR after the first course of treatment. Within this cohort, 6 patients were classified as relapsed/refractory (6/13). 4 patients underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT), of which two achieved long-term survival. The median follow-up time was 12 (2.1-65.0) months, while the median overall survival (OS) and relapse-free survival (RFS) were recorded as 11.4 months and 9.6 months, respectively. CONCLUSION The most common type of NUP98 rearrangement in adults AML patients is NUP98::HOXA9 , which is often accompanied by somatic mutations in WT1, TET2, and FLT3-ITD. These patients are prone to relapse, have short survival time, and generally face poor prognoses. Hopefully, utilization of the AZA+VEN regimen is anticipated to enhance the rate of induced remission in the patients, and some patients may prolong their survival through allo-HSCT. However, more effective treatment methods are still needed to improve the overall prognosis of these patients.
Humans ; Adult ; Leukemia, Myeloid, Acute/genetics* ; Middle Aged ; Prognosis ; Nuclear Pore Complex Proteins/genetics* ; Oncogene Proteins, Fusion/genetics* ; Mutation ; Male ; Female ; Young Adult ; Homeodomain Proteins/genetics*

Ursodeoxycholic acid (UDCA) is a naturally occurring, low-toxicity, and hydrophilic bile acid (BA) in the human body that is converted by intestinal flora using primary BA. Solute carrier family 7 member 11 (SLC7A11) functions to uptake extracellular cystine in exchange for glutamate, and is highly expressed in a variety of human cancers. Retroperitoneal liposarcoma (RLPS) refers to liposarcoma originating from the retroperitoneal area. Lipidomics analysis revealed that UDCA was one of the most significantly downregulated metabolites in sera of RLPS patients compared with healthy subjects. The augmentation of UDCA concentration (≥25 μg/mL) demonstrated a suppressive effect on the proliferation of liposarcoma cells. [¹⁵N₂]-cystine and [¹³C₅]-glutamine isotope tracing revealed that UDCA impairs cystine uptake and glutathione (GSH) synthesis. Mechanistically, UDCA binds to the cystine transporter SLC7A11 to inhibit cystine uptake and impair GSH de novo synthesis, leading to reactive oxygen species (ROS) accumulation and mitochondrial oxidative damage. Furthermore, UDCA can promote the anti-cancer effects of ferroptosis inducers (Erastin, RSL3), the murine double minute 2 (MDM2) inhibitors (Nutlin 3a, RG7112), cyclin dependent kinase 4 (CDK4) inhibitor (Abemaciclib), and glutaminase inhibitor (CB839). Together, UDCA functions as a cystine exchange factor that binds to SLC7A11 for antitumor activity, and SLC7A11 is not only a new transporter for BA but also a clinically applicable target for UDCA. More importantly, in combination with other antitumor chemotherapy or physiotherapy treatments, UDCA may provide effective and promising treatment strategies for RLPS or other types of tumors in a ROS-dependent manner.

Objective To investigate the effect of varying blood pressure stratification on renal function in the diabetic population.Methods A prospective cohort study was conducted,enrolling 9 489 diabetic patients from a total of 101 510 Kailuan Group employees who underwent health examinations between July 2006 and October 2007.The follow-up period was(8.6±4.0)years.Participants were categorized into four groups based on their baseline blood pressure levels:normal blood pressure(systolic blood pressure<120 mmHg and diastolic blood pressure<80 mmHg),elevated blood pressure(systolic blood pressure 120-130 mmHg and diastolic blood pressure<80 mmHg),stage 1 hypertension(systolic blood pressure 130-140 mmHg and/or diastolic blood pressure 80-90 mmHg),and stage 2 hypertension(systolic blood pressure≥140 mmHg and/or diastolic blood pressure≥90 mmHg).The incidence density of chronic kidney disease(CKD)was compared among these groups.A multivariate Cox proportional hazards regression model was employed to assess the effects of different blood pressure levels on renal function in diabetic patients,with the stability of the results confirmed using a multivariate time-dependent Cox proportional hazards model.Sensitivity analysis was conducted after excluding cases of cardiovascular disease(CVD)during follow-up,and cases using antihypertensive and antidiabetic medications at baseline.Results(1)At baseline,stage 1 hypertension patients demonstrated statistically significant higher differences with age and body mass index(BMI)compared to normal blood pressure group(P<0.05).(2)By the end of the follow-up,2 294 cases of CKD were identified,including 1 117 cases of estimated glomerular filtration rate(eGFR)decline and 1 575 cases of urinary protein.The incidences density of CKD,eGFR decline and urinary protein for stage 1 hypertension group were 39.4,16.3 and 25.5 per thousand person-years,respectively,all of which were statistically significant different from normal blood pressure group(log-rank test,P<0.01).(3)Multivariate Cox regression analysis revealed that,compared to the normal blood pressure group,stage 1 hypertension was associated with a 29%increased risk of CKD(HR=1.29,95%CI 1.09-1.52)and a 40%increased risk of eGFR decline(HR=1.40,95%CI 1.08-1.80)in diabetic individuals.Conclusion Stage 1 hypertension significantly increases the risk of CKD and eGFR decline in diabetic individuals,with a particularly notable effect on the risk of eGFR decline.

Severe cerebrovascular disease is a kind of severe cerebrovascular disease involving disturbance of consciousness,which corresponds to the viscera of stroke in traditional Chinese medicine(TCM).Rooted in the TCM classics such as Huang Di Nei Jing(The Yellow Emperor's Inner Classic)and Shang Han Lun(Treatise on Cold Damage),Professor WU Hai-Ke studied the TCM pathogenesis theory recorded in the chapter of Profound and Important Theory in Plain Questions(Su Wen)carefully.Based on its clinical practice and inherited the traditional four diagnostic methods of inspection,auscultation-olfaction,interrogation,and palpation,Professor WU Hai-Ke simplified and created the six-differentiation method for the syndrome differentiation of patients with severe cerebrovascular disease:distinguishing the mind to learn the progression of the disease,distinguishing the complexion to know the exuberance or decline of qi and blood,distinguishing the tongue picture to predict the aggravation or relief of the disease,distinguishing the pulse condition to judge the prognosis,distinguishing the breath to know the deficiency or excess of zang-fu organs,and distinguishing cold-heat to identify the exterior,interior,yin and yang.The six-differentiation method highlights the significance of mind,complexion,tongue picture,pulse condition,breath,and cold-heat in the syndrome differentiation of patients with severe cerebrovascular disease.The clinical information of six-differentiation method is easy to obtain,and the method presents the characteristics and advantages of TCM diagnostic methods in the syndrome differentiation of patients with severe cerebrovascular disease,which will provide reference for the establishment of clinical diagnosis and treatment norms of TCM for severe cerebrovascular disease.

Objective To summarize the acupoints and parameters commonly used in the treatment of vascular cognitive impairment(VCI)by electro-acupuncture(EA)through the visual data mining technique to provide a reference basis for clinical treatment.Methods The clinical studies of EA on the treatment of VCI were searched in CNKI,Wanfang,VIP,CBM,PubMed,Embase,Cochrane Library,web of science and other major databases.The literature is managed by Note Express and the database is established by Excel.The frequency of selected acupoints,frequency,meridian tropism,parameter frequency and frequency of used acupoints are counted.Factor analysis is carried out by SPSS 21.0 software.SPSS Modeler 18.3 software is used to analyze association rules and co-occurrence network,and the analysis results are visualized by Cytoscape 3.9.1 software.Results Finally,155 papers were included,containing 155 acupoint prescriptions and 157 parameter prescriptions.Acupoint prescriptions involved 100 acupoints with a total frequency of 856 times;parameter prescriptions involved 33 parameters with a total frequency of 788 times.Conclusion At present,there is a big difference between the clinical studies,and there is no recognized acupoint and parameter for EA treatment of VCI.By further summarizing the law of EA acupuncture point and parameter,the study has sorted out the law of commonly used acupoints,meridian tropism,compounding and parameter selection for EA treatment of VCI.It was concluded that the selection of acupoints mainly started from the three aspects of deficiency,phlegm and stasis,focusing on the combination of local and distal selection of acupoints,through the identification of internal organs and meridians,to achieve the simultaneous regulation of the heart,spleen and kidney,and to take into account both the symptoms and the root cause,and to play the roles of opening the orifices to wake up mind,calming mind and benefiting intellect,strengthening the spleen and tonifying the kidneys,and invigorating blood circulation to remove stasis.The parameters of EA are recommended to be sparse and dense wave,low frequency,as tolerated by the patient,30 minutes/times,1 time/day,5 times/week as the main combinations,which can provide a certain reference basis for clinical decision-making.

Objective:To study the feasibility of magnetic resonance imaging(MRI)technique with amide proton transfer(APT)in predicting the prognosis of cerebral stroke.Methods:A total of 71 patients with acute cerebral stroke who admitted to the Nanjing First Hospital,Nanjing Medical University from September 2022 to May 2023 were selected.All of them underwent the test of National Institute of Health Stroke Scale(NIHSS),and received the MRI examination with chemical exchange saturation transfer(CEST).According to the modified Rankin scale(mRS)values of 1-month follow-up,they were divided into favorable recovery group(mRS<2,44 cases)and poor group(mRS≥2,27 cases).The asymmetric magnetization transfer ratio(MTRasym)image(APT)was obtained by analyzing data with special software.And then,the difference(△APTw)of APT values between ischemic zone and contralateral normal tissue was further calculated.The △APTw values of two groups were compared and analyzed,and the Pearson correlation analysis was adopted to analyze the correlation among △APTw,NIHSS and mRS.The receiver operating characteristics(ROC)curve was drawn,and the area under curve(AUC)of ROC curve was calculated.Results:There were significant positive correlations among △APTw,NIHSS and mRS scores(R2=0.659,0.522,P<0.001),and the differences of △APTW,NIHSS and mRS scores between the favorable recovery group and poor group were significant(t=5.73,6.36,13.92,P<0.05),respectively.The AUC value was 0.886,and the sensitivity and specificity of prediction were respectively 77.8%and 95.5%.The positive and negative predictive values were respectively 91.3%and 87.5%.Conclusion:APT imaging technique has feasibility in predicting the prognosis of acute cerebral ischemic stroke.

This paper applied gas chromatography-mass spectrometry (GC-MS), network pharmacology and nuclear magnetic resonance hydrogen spectroscopy (¹H NMR) metabolomics techniques to study the material basis and mechanism of action of Ning Shen Essential Oil in anti-insomnia. The main volatile components of Ning Shen Essential Oil were analyzed by gas chromatography-mass spectrometry (GC-MS), and the insomnia-related targets were predicted using the Traditional Chinese Medicine Systematic Pharmacology Database and Analytical Platform (TCMSP) and the databases of GeneCards, OMIM and Drugbank. The insomnia model of rats was replicated by intraperitoneal injection of 4-chloro-DL-phenylalanine (PCPA). Animal experiments were approved by the Animal Ethics Committee of Shandong University of Traditional Chinese Medicine (Ethics No.: SDUTCM20221025010). The modulating effect of Compound Ning Shen Essential Oil on anxiety behavior of rats was evaluated by behavioral related indexes. The serum levels of corticotropin-releasing hormone (CRH), adrenotropic corticotropic hormone (ACTH) and melatonin (MT) were measured by enzyme-linked immunoassay (ELISA). Rat serum and hippocampus were taken for nuclear magnetic resonance (¹H NMR) metabolomics to detect the changes of endogenous metabolites in rat serum hippocampus, to designate the differential metabolites and to construct metabolic pathways. The results showed that the exercise distance in the open field experiment and the number of times and time to enter the open arm in the elevated cross maze experiment of the rats in the model group were significantly reduced (P < 0.05, P < 0.01). The behavioral indexes of rats improved to different degrees after the administration of Ning Shen Essential Oil. The serum CRH and ACTH levels of rats in the model group increased significantly (P < 0.05, P < 0.01), and the MT level decreased significantly (P < 0.01); After the intervention, serum CRH and ACTH levels were reduced to different degrees, and MT levels could be regressed. ¹H NMR metabolomics screened 10 potential biomarkers related to insomnia, which involved in 6 potential metabolic pathways. A total of 35 components of Ning Shen Essential Oil were detected by GC-MS, the main component targets of Ning Shen Essential Oil and insomnia disease targets were intersected, a total of 172 intersecting genes were screened, and 26 core targets were identified. The study demonstrated that Ning Shen Essential Oil had protective effects against PCPA-induced insomnia in rats, which was probably correlated with regulation of the hypothalamic-pituitary-adrenal axis (HPA) related hormones and metabolism of amino acids, lipids and choline.