Objective To establish an individualized nomogram model and evaluate its efficacy to provide a possible evaluation basis for the prognosis of lower third and abdominal part of oesophageal adenocarcinoma (EAC). Methods Lower third and abdominal part of EAC patients from 2010 to 2015 were chosen from the SEER Research Plus Database (17 Regs, 2022nov sub). The patients were randomly allocated to the training cohort and the internal validation cohort with a ratio of 7∶3 using bootstrap resampling. The Cox proportional hazards regression analysis was used to determine significant contributors to overall survival (OS) in EAC patients, which would be elected to construct the nomogram prediction model. C-index, calibration curve and receiver operating characteristic (ROC) curve were performed to evaluate its efficacy. Finally, the efficacy to evaluate the OS of EAC patients was compared between the nomogram prediction model and TNM staging system. Results In total, 3945 patients with lower third and abdominal part of EAC were enrolled, including 3475 males and 470 females with a median age of 65 (57-72) years. The 2761 patients were allocated to the training cohort and the remaining 1184 patients to the internal validation cohort. In the training and the internal validation cohorts, the C-index of the nomogram model was 0.705 and 0.713, respectively. Meanwhile, the calibration curve also suggested that the nomogram model had a strong capability of predicting 1-, 3-, and 5-year OS rates of EAC patients. The nomogram also had a higher efficacy than the TNM staging system in predicting 1-, 3-, and 5-year OS rates of EAC patients. Conclusion This nomogram prediction model has a high efficiency for predicting OS in the patients with lower third and abdominal part of EAC, which is higher than that of the current TNM staging system.

ObjectiveTo explore the therapeutic effect of Xuebijing injection （XBJ） on severe acute pancreatitis induced acute lung injury （SAP-ALI） by regulating formyl peptide receptors （FPRs）/nucleotide-binding oligomerization domain-like receptor 3 （NLRP3） inflammatory pathway. MethodsSixty rats were randomly divided into a sham group， a SAP-ALI model group， low-， medium-， and high-dose XBJ groups （4， 8， and 12 mL·kg^-1）， and a positive drug （BOC2， 0.2 mg·kg^-1） group. For the sham group， the pancreas of rats was only gently flipped after laparotomy， and then the abdomen was closed， while for the remaining five groups， SAP-ALI rat models were established by retrograde injection of 5% sodium taurocholate （Na-Tc） via the biliopancreatic duct. XBJ and BOC2 were administered via intraperitoneal injection once daily for 3 d prior to modeling and 0.5 h after modeling. Blood was collected from the abdominal aorta 6 h after the completion of modeling， and the expression of interleukin （IL）-1β， IL-6， and tumor necrosis factor-α （TNF-α） in plasma was measured by enzyme-linked immunosorbent assay （ELISA）. The amount of ascites was measured， and the dry-wet weight ratios of pancreatic and lung tissue were determined. Pancreatic and lung tissue was taken for hematoxylin-eosin （HE） staining to observe pathological changes and then scored. The protein expression levels of FPR1， FPR2， and NLRP3 in lung tissue were detected by the immunohistochemical method. Western blot was used to detect the expression of FPR1， FPR2， and NLRP3 in lung tissue. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） was used to detect the mRNA expression of FPR1， FPR2， and NLRP3 in lung tissue. ResultsCompared with the sham group， the SAP-ALI model group showed significantly decreased dry-wet weight ratio of lung tissue （P<0.01）， serious pathological changes of lung tissue， a significantly increased pathological score （P<0.01）， and significantly increased protein and mRNA expression levels of FPR1， FPR2， and NLRP3 in lung tissue （P<0.01）. After BOC2 intervention， the above detection indicators were significantly reversed （P<0.01）. After treatment with XBJ， the groups of different XBJ doses achieved results consistent with BOC2 intervention. ConclusionXBJ can effectively improve the inflammatory response of the lungs in SAP-ALI rats and reduce damage. The mechanism may be related to inhibiting the expression of FPRs and NLRP3 in lung tissue， which thereby reduces IL-1β and simultaneously antagonize the release of inflammatory factors IL-6 and TNF-α.

AIM: To explore the factors affecting the whole-eye astigmatism after pterygium excision combined with autologous limbal stem cell transplantation.METHODS: A retrospective analysis was conducted on the medical records of 42 patients(42 eyes)with primary pterygium admitted in the ophthalmology department of Xijing Hospital from January 2023 to October 2023. They underwent pterygium excision combined with autologous limbal stem cell transplantation. The maximum invasion depth of pterygium into the cornea was measured with anterior segment optical coherence tomography(AS-OCT)before operation, the length of the pterygium invading cornea, the width of the limbus and the area of the invading cornea were measured during the operation, and three-dimensional values of corneal astigmatism of anterior segment, index of surface variance(ISV), index of vertical asymmetry(IVA), best corrected visual acuity(BCVA)and whole-eye astigmatism were collected before and at 1 mo after surgery. Patients with astigmatism ≤0.50 D or >0.50 D of the whole eye at 1 mo after surgery were assigned to group A and B, respectively. The differences of clinical data before and at 1 mo after surgery between the two groups, and the correlation between pre-operative clinical indicators and whole-eye astigmatism were analyzed. The decision tree algorithm was performed to explore the influencing factors of whole-eye astigmatism at 1 mo postoperatively.RESULTS: The maximum invasion depth of pterygium in the group A was significantly less than that in the group B [80.00(40.00, 180.00)μm vs 175.00(123.00, 190.00)μm, P=0.002]. Preoperative BCVA(LogMAR), whole-eye astigmatism, cornea astigmatism, ISV, IVA and maximum invasion depth of pterygium were positively correlated with whole-eye astigmatism at 1 mo after surgery(rs=0.317, P=0.041; rs=0.545, P<0.001; rs=0.448, P=0.003; rs=0.389, P=0.011; rs=0.382, P=0.013; rs=0.391, P=0.010). The decision tree algorithm screened out two influential factors: the maximum invasion depth of pterygium into the cornea and preoperative whole-eye astigmatism. The risk of whole-eye astigmatism >0.50 D at 1 mo after operation was higher with maximum invasion depth of pterygium into the cornea >95 μm than that with ≤95 μm. Among the patients with whole-eye astigmatism >2.63 D before operation, the probability of residual whole-eye astigmatism >0.50 D was 88.9%, and the predictive model AUC was 0.804.CONCLUSION: The whole-eye astigmatism after pterygium resection is mainly affected by the maximum invasion depth of pterygium into the cornea and preoperative whole-eye astigmatism. When the maximum invasion depth of pterygium into the corneal is >95 μm and the whole-eye stigmatism is >2.63 D before surgery, the patient should receive surgical treatment as soon as possible in order to obtain good clinical benefits.

Objective To investigate the prognosis of patients with brain abscess and related influencing factors. Methods A retrospective analysis was conducted for the patients with brain abscess who were consecutively admitted to Department of Neurology， Xijing Hospital of Air Force Medical University， from January 2010 to March 2022， and according to the Glasgow Outcome Scale（GOS） score at discharge， the patients were divided into good prognosis group （GOS score>3 points） and poor prognosis group（GOS score≤3 points）. The t-test， the Wilcoxon rank-sum test， the chi-square test， and the Logistic regression analysis were used to investigate the influencing factors for prognosis. Results Among the 173 patients with brain abscess，69（39.9%） had a poor prognosis， and 104 （60.1%） had a good prognosis. There were significant differences between the two groups in age， headache， seizure， coma events， focal neurological deficits， dexamethasone treatment， and cerebellar abscess （P<0.05）.The multivariate logistic regression analysis showed that age （OR=0.042，95%CI 1.001‒1.041，P=0.042）， seizure（OR=2.881，95%CI 1.172‒7.083，P=0.021）， and coma events （OR=2.694， 95%CI 1.195‒6.072， P=0.017） were significant predictive factors for poor prognosis. Conclusion Age， seizure， and coma events are major factors associated with poor prognosis. Age is an uncontrollable factor， and therefore， timely prevention and management of seizure and coma events can reduce the incidence rate of poor prognosis.
Prognosis

BACKGROUND: The primary limitation to kidney transplantation is organ shortage. Recent progress in gene editing and immunosuppressive regimens has made xenotransplantation with porcine organs a possibility. However, evidence in pig-to-human xenotransplantation remains scarce, and antibody-mediated rejection (AMR) is a major obstacle to clinical applications of xenotransplantation. METHODS: We conducted a kidney xenotransplantation in a brain-dead human recipient using a porcine kidney with five gene edits (5GE) on March 25, 2024 at Xijing Hospital, China. Clinical-grade immunosuppressive regimens were employed, and the observation period lasted 22 days. We collected and analyzed the xenograft function, ultrasound findings, sequential protocol biopsies, and immune surveillance of the recipient during the observation. RESULTS: The combination of 5GE in the porcine kidney and clinical-grade immunosuppressive regimens prevented hyperacute rejection. The xenograft kidney underwent delayed graft function in the first week, but urine output increased later and the single xenograft kidney maintained electrolyte and pH homeostasis from postoperative day (POD) 12 to 19. We observed AMR at 24 h post-transplantation, due to the presence of pre-existing anti-porcine antibodies and cytotoxicity before transplantation; this AMR persisted throughout the observation period. Plasma exchange and intravenous immunoglobulin treatment mitigated the AMR. We observed activation of latent porcine cytomegalovirus toward the end of the study, which might have contributed to coagulation disorder in the recipient. CONCLUSIONS 5GE and clinical-grade immunosuppressive regimens were sufficient to prevent hyperacute rejection during pig-to-human kidney xenotransplantation. Pre-existing anti-porcine antibodies predisposed the xenograft to AMR. Plasma exchange and intravenous immunoglobulin were safe and effective in the treatment of AMR after kidney xenotransplantation.
Transplantation, Heterologous/methods* ; Kidney Transplantation/methods* ; Heterografts/pathology* ; Immunoglobulins, Intravenous/administration & dosage* ; Graft Survival/immunology* ; Humans ; Animals ; Sus scrofa ; Graft Rejection/prevention & control* ; Kidney/pathology* ; Gene Editing ; Species Specificity ; Immunosuppression Therapy/methods* ; Plasma Exchange ; Brain Death ; Biopsy ; Male ; Aged

[摘 要] 目的：探讨环磷腺苷效应元件结合蛋白（CREB）对前列腺癌细胞恶性生物学行为的影响。方法：常规培养前列腺癌细胞PC3，用转染试剂将过表达对照质粒，CREB过表达质粒（CREB-oe)、敲减对照序列（si-NC）和si-CREB序列转染至PC3细胞，分为vector，CREB-oe、si-NC和si-CREB组。用划痕愈合实验、Transwell小室实验和流式细胞术分别检测各组细胞的迁移、侵袭能力和细胞周期情况。用CRISPR/cas9技术构建CREB敲除的PC3细胞，用PC3细胞移植瘤实验检测CREB敲除对移植瘤生长的影响。结果：在PC3细胞中成功地敲减或过表达了CREB（均P < 0.01），过表达或敲减CREB均可明显促进或抑制PC3细胞的迁移、侵袭能力（均P < 0.01），过表达CREB可促使PC3细胞进入S期，而敲减CREB表达则使PC3细胞阻滞于G1期（均P < 0.01）。成功地构建了CREB敲除PC3细胞，敲除CREB可明显抑制PC3细胞移植瘤的生长（P < 0.01）。结论：敲减或敲除CREB能够抑制PC3细胞的迁移和侵袭，并使其阻滞于G1期，进而抑制移植瘤的生长。

Objective To evaluate the value of postoperative radiotherapy (PORT) in patients with stage ⅢA-N2 non-small cell lung cancer who received complete resection and chemotherapy. Methods Patients with stage ⅢA-N2 non-small cell lung cancer who received complete resection and chemotherapy were chosen from the SEER Research Plus Database [17 Registries, November 2012 Submission (2000-2019)]. The patients were divided into a PORT group and a non-PORT group according to whether the PORT was used. To balance baseline characteristics between non-PORT and PORT groups, R software was used to conduct a propensity score matching (PSM) with a ratio of 1 : 1 and a matching tolerance of 0.01. Both the Cox regression analysis and Kaplan-Meier survival analysis were conducted to evaluate the value of PORT in terms of overall survival (OS) and disease-specific survival (DSS). Results In total, 2468 patients with stage ⅢA-N2 non-small cell lung cancer were enrolled, including 1078 males and 1390 females with a median age of 65 (58-71) years. There were 1336 patients in the PORT group, and 1132 patients in the non-PORT group. Cox regression analysis showed that PORT was not significantly associated with OS (multivariate analysis: HR=1.051, 95%CI 0.949-1.164, P=0.338) and DSS (multivariate analysis: HR=1.094, 95%CI 0.976-1.225, P=0.123). No statistical difference was found in the OS or DSS between non-PORT group and PORT group after PSM analysis (P＞0.05). Conclusion PORT does not have a survival benefit for patients with stage ⅢA-N2 non-small cell lung cancer who received complete resection and chemotherapy.

OBJECTIVE To investigate the induction of apoptosis in hepatocellular carcinoma cells by polyphyllin 9 （PP9） through the regulation of the Fas/Fas ligand （FasL） signaling pathway， and its inhibitory effect on the growth of transplanted tumor in nude mice. METHODS Based on the screening of cell lines and intervention conditions， HepG2 cells were selected as the experimental subject to investigate the effects of 2 μmol/L and 4 μmol/L PP9 treatment on cell colony formation activity， apoptosis rate， as well as the protein expressions of Fas， FasL， cleaved caspase-8 and cleaved caspase-3. Additionally， Fas inhibitor KR- 33493 was introduced to investigate the underlying mechanism of PP9’s anti-hepatocellular carcinoma activity. Using HepG2 cell tumor-bearing nude mice model as the object， and 5-fluorouracil （20 mg/kg） as the positive control， the effects of 10 mg/kg PP9 on tumor volume， tumor mass， and the protein expressions of the nuclear proliferation-associated antigen Ki-67 and cleaved caspase-3 in tumor-bearing nude mice were investigated. RESULTS Compared with the control group， 2， 4 μmol/L PP9 significantly decreased the number of clones and the clone formation rate of cells， but significantly increased the apoptosis rate， the protein expressions of Fas， FasL， cleaved caspase-8 and cleaved caspase-3 （P＜0.05 or P＜0.01）. However， the combination of Fas inhibitor KR-33493 could significantly reverse the effect of PP9 on the up-regulation of proteins related to the Fas/FasL signaling pathway （P＜0.01）. Compared with the control group， the tumor volume （on day 27）， mass and protein expression of Ki- 67 in nude mice of the PP9 group were significantly decreased， while the protein expression of cleaved caspase-3 was significantly increased （P＜0.01）. CONCLUSIONS PP9 can induce apoptosis of HepG2 cells by activating the Fas/FasL signaling pathway. Meanwhile， PP9 can also effectively inhibit the growth of transplanted tumors in nude mice.

Objective To construct a predictive model for cerebral small vessel disease (CSVD) MRI burden based on β2-microglobulin (β2-MG) and lipoprotein(a) [Lp(a)], analyze its predictive value, and validate the model. Methods A total of 138 CSVD patients admitted to Anhui No.2 Provincial People’s Hospital from February 2023 to August 2024 were enrolled. Patients were divided into a low-burden group (n=63) and a moderate/severe burden group (n=75) according to the CSVD MRI burden scoring criteria. The related clinical data were compared between the two groups. Binary logistic regression analysis was used to identify independent factors for CSVD moderate/severe MRI burden. A nomogram predictive model was constructed based on these factors and its performance was evaluated. Results The proportions of male patients, as well as those with a history of diabetes or hypertension, were significantly higher in the moderate/severe burden group than those in the low burden group. Additionally, the age of patients in the moderate/severe burden group was significantly older, and the levels of β2-MG, Lp(a), and homocysteine (Hcy) were higher than those in the low burden group (P＜0.01). Binary logistic regression analysis revealed that hypertension, diabetes, β2-MG, and Lp(a) were independent factors for CSVD moderate/severe MRI burden (P＜0.05). The nomogram predictive model based on these four factors had a cut-off value of 0.467 0, with an area under curve (AUC) of 0.838 7 (95%CI 0.760 8-0.916 6) in the training set (n＝97) and 0.854 1 (95%CI 0.742 1-0.966 1) in the internal validation set (n＝41) . The calibration curve demonstrated good agreement between predicted and observed values. Decision curve analysis (DCA) indicated that the nomogram model had good clinical utility. Conclusions The nomogram model based on β2-MG and Lp(a) has high predictive performance in assessing the risk of CSVD moderate/severe MRI burden, with good discrimination and calibration.

Large language models (LLMs) such as ChatGPT, Claude, Llama, and Qwen are emerging as transformative technologies for the diagnosis and treatment of various diseases. With their exceptional long-context reasoning capabilities, LLMs are proficient in clinically relevant tasks, particularly in medical text analysis and interactive dialogue. They can enhance diagnostic accuracy by processing vast amounts of patient data and medical literature and have demonstrated their utility in diagnosing common diseases and facilitating the identification of rare diseases by recognizing subtle patterns in symptoms and test results. Building on their image-recognition abilities, multimodal LLMs (MLLMs) show promising potential for diagnosis based on radiography, chest computed tomography (CT), electrocardiography (ECG), and common pathological images. These models can also assist in treatment planning by suggesting evidence-based interventions and improving clinical decision support systems through integrated analysis of patient records. Despite these promising developments, significant challenges persist regarding the use of LLMs in medicine, including concerns regarding algorithmic bias, the potential for hallucinations, and the need for rigorous clinical validation. Ethical considerations also underscore the importance of maintaining the function of supervision in clinical practice. This paper highlights the rapid advancements in research on the diagnostic and therapeutic applications of LLMs across different medical disciplines and emphasizes the importance of policymaking, ethical supervision, and multidisciplinary collaboration in promoting more effective and safer clinical applications of LLMs. Future directions include the integration of proprietary clinical knowledge, the investigation of open-source and customized models, and the evaluation of real-time effects in clinical diagnosis and treatment practices.
Humans ; Large Language Models ; Tomography, X-Ray Computed