To develop and validate a model for predicting intensive care unit (ICU) mortality risk in patients with malignant tumors complicated by acute respiratory failure (ARF) based on an explainable machine learning framework.

Background Co-exposure to noise and microwave radiation occurs frequently. The central nervous system has been identified as a sensitive target organ for both noise and microwave exposure individually, and the underlying mechanisms remain poorly understood. The specific biological effects resulting from co-exposure to these two factors have yet to be fully elucidated. Objective To clarify the effects of co-exposure to noise and microwave on neurobehavior and hippocampal tissue structure, and to explore the underlying mechanism through the assessment of serum cytokines. Methods C57BL/6N mice were selected and randomly assigned to a blank control group, a noise group, a microwave group, and a combined noise & microwave exposure group. To establish the exposure models, the noise group was subjected to broadband noise at 100 dB for 2 h, while the microwave group received radiation at a central frequency of 9.375 GHz with an average power density of 12 mW·cm⁻² and a specific absorption rate of 2.58 W·kg⁻¹ for 15 min. Open field and tail suspension tests assessed anxiety-like emotional behaviour; novel object recognition and Y-maze tests evaluated cognitive function. Histological changes in hippocampal tissue were examined using haematoxylin and eosin (HE) staining, and Nissl staining under light microscopy. Serum cytokine levels were measured using radioimmunoassay and enzyme-linked immunosorbent assay (ELISA). Results After 3 d of exposure, the noise, microwave, and combined exposure groups showed significant reductions in exploration frequency, duration, and distance within the central zone of the open field test compared to the control group (P < 0.01); the combined exposure group exhibited increased ratios of peripheral-to-central exploration time and distance (P < 0.05). After 7 d of exposure, compared with the control group, the noise group maintained a decrease in central zone exploration time (P < 0.01), while the combined exposure group showed persistent decline across all central zone metrics (P < 0.05) and elevated peripheral-to-central ratios (P < 0.05); compared to the microwave group, the combined exposure group showed significant less time in the central zone (P < 0.05) and higher peripheral-to-central ratios (P < 0.05). Regarding behaviour and cognition, compared with the control group, the combined exposure group showed increased immobility time in the tail suspension test after 3 d of exposure (P < 0.01). At this interval, all exposure groups demonstrated reduced frequency and duration of novel object recognition (P < 0.05), with the combined exposure group showing a marked decrease in novel arm exploration time (P < 0.01). After 7 d of exposure, compared with the control group, the noise group showed reduced novel object recognition frequency (P < 0.05), and both the noise and microwave groups exhibited decreased novel arm exploration time (P < 0.05). Pathological alterations including an increased number of hyperchromatic nuclei and depleted Nissl bodies were observed in the CA3 and DG regions across all exposure groups with the most severe lesions observed in the combined exposure group. Serum levels of central nervous system-specific protein β (S-100β), glial fibrillary acidic protein (GFAP), and corticosterone (CORT) were significantly elevated in all exposure groups compared with the control group (P < 0.05). Aquaporin-4 (AQP4) levels increased in the combined exposure group (P < 0.05), while CXC chemokine ligand 10 (CXCL10) levels rose in both the noise and combined groups compared with the control group (P < 0.05). Specifically, S-100β and CXCL10 levels in the combined exposure group were higher than those in the microwave group (P < 0.05); moreover, levels of S-100β, GFAP, CORT, AQP4, and CXCL10 in the combined exposure group were significantly higher than those in the noise group (P < 0.05). Conclusion Combined exposure to noise and microwave radiation induces pathological changes in the hippocampus of mice, increases levels of serum stress hormones and neuro-specific biomarkers. These impairments are more severe than those observed following single-factor exposure. The underlaying mechanism may be related to systemic stress response, neuronal damage, astrocyte activation, and changes in blood-brain barrier permeability, leading to emotional behavioral abnormalities and cognitive decline.

Objective: To investigate the serological identification and blood group gene sequencing analysis of two rare cases of K phenotype producing high-frequency antigen antibodies (anti-Ku), and to study the serological interrelationship between K cells and the high-frequency antigen antibody anti-KL. Methods: Serological methods were used to identify the antigen phenotypes of the ABO, Rh, and Kell blood group systems and to screen for and identify unexpected antibodies in the two patients. The characteristics of the unexpected antibodies were verified by the indirect antiglobulin test (IAT) using papain or dithiothreitol (DTT) -treated screening cells. The titer of anti-Ku was determined via the tube method using DTT-treated plasma. The Kell blood group genotype was determined by gene sequencing. The distinctive antigenicity of K cells was validated through their reactivity with anti-KL in IAT, and absorption-elution techniques were employed to corroborate the type of anti-KL. Results: Serological findings: Case 1 was blood group O, CCDee; Case 2 was blood group A, CCDee. Both cases exhibited the Kell phenotype: K-k-, Kp (a-b-). High-frequency antigen antibodies were detected in the plasma of both patients. The reactivity of these antibodies was slightly enhanced with papain-treated screening cells but became negative with DTT-treated cells. The anti-Ku (IgG) titer for Case 1 was 64. For Case 2, the anti-Ku (IgM) titer was<1, and the anti-Ku (IgG) titer was 32. Gene sequencing revealed that both cases harbored a homozygous c.715G>T mutation in the KEL gene, corresponding to the genotype KEL02N.24, consistent with the rare K phenotype. The unique high expression of the Kx antigen on K cells was confirmed through the antibody characteristics of anti-KL. Absorption-elution techniques demonstrated that K cells could separate anti-Km and anti-Kx, thereby supporting the classification of anti-KL. Conclusion: Serological and molecular biological assays identified both patients as having the rare Kell-null (K ) phenotype. If such rare blood types go undetected in transfusion medicine, the administration of standard blood products can readily induce the production of high-frequency antigen antibodies such as anti-Ku, potentially leading to a transfusion crisis due to the subsequent difficulty in finding compatible blood. The serological relationship between K cells and anti-KL clarified the characteristic high expression of the Kx antigen on K phenotype erythrocytes and concurrently supported the typological features of the rare high-frequency antibody anti-KL. This represents the first such verified report in China.

Plant-derived extracellular vesicles (PDEVs) are nanoscale extracellular vesicles secreted by plant cells, characterized by a lipid bilayer structure. These vesicles carry a variety of bioactive molecules, including proteins, nucleic acids, and lipids, and play essential roles in intercellular communication and physiological regulation in plants. Compared to animal-derived extracellular vesicles, PDEVs offer several advantages, such as a broad range of sources, high biocompatibility, low immunogenicity, and low production costs. Furthermore, PDEVs have demonstrated remarkable potential as natural nanocarriers for drug delivery, due to their ability to efficiently traverse biological barriers, such as the blood-brain barrier, making them promising candidates for drug delivery systems. This review systematically elaborates on the complex composition of PDEVs, which consists of lipids, proteins, and nucleic acids, the typical structural characteristics of their lipid bilayers ranging from 30 to 150 nm, and their versatile loading capabilities as drug carriers, efficiently encapsulating various types of therapeutic agents such as hydrophilic small molecules, hydrophobic drugs, nucleic acids, and proteins. We systematically summarize the recent advancements in strategies for enhancing the loading efficiency of PDEVs, which include methods such as co-incubation, ultrasound-assisted loading, electroporation, freeze-thaw cycles, and microfluidic technology. These techniques are evaluated based on their underlying principles, suitable drug types, and their respective advantages. In addition to loading strategies, we focus on the engineered approaches to achieve targeted delivery using PDEVs, such as genetic engineering modifications, chemical ligand conjugation, membrane fusion technology, and polyethylene glycol (PEG) modification. We discuss the mechanisms of these strategies in enhancing targeting efficiency, prolonging in vivo circulation time, and improving therapeutic efficacy. Further, this review highlights the application of PDEVs in various disease models, including tumor, skin inflammation, metabolic disorders, and neurodegenerative diseases, showcasing their therapeutic potential as multifunctional delivery platforms. The ability of PDEVs to encapsulate diverse therapeutic agents and target specific tissues or cells opens up new avenues for the treatment of complex diseases, offering advantages over conventional drug delivery systems. However, despite the promising applications of PDEVs, several challenges remain in their development and clinical translation. These challenges include variability in source materials, standardization of preparation processes, quality control, scalability of production, and the need for clinical validation. To overcome these obstacles, the integration of advanced technologies such as artificial intelligence-assisted design and multi-omics analysis is proposed as a way to facilitate the precise development of PDEVs. These emerging technologies hold the potential to further enhance the precision and effectiveness of plant-based drug delivery systems, ultimately advancing the field of precision medicine. In conclusion, the use of PDEVs as a platform for drug delivery represents a promising area of research with the potential to revolutionize therapeutic strategies. Their ability to encapsulate and deliver a wide variety of bioactive molecules, along with their inherent advantages in biocompatibility and versatility, makes them a valuable tool in the development of more efficient and targeted therapeutic interventions. Continued research and innovation in this field will pave the way for the clinical implementation of PDEVs in the treatment of various diseases, offering new hope for more effective and sustainable therapeutic options.

OBJECTIVE To explore the efficacy and safety of toludesvenlafaxine in the treatment of patients with major depressive disorder （MDD） with anhedonia. METHODS This retrospective study included 160 patients with MDD with anhedonia who were treated at Hebei Mental Health Center from May 2023 to August 2025. These patients were divided into a control group （ n ＝81） and an observation group （ n ＝79） according to treatment regimens. All patients received transcranial magnetic stimulation therapy. On this basis，the control group was treated with Sertraline Hydrochloride Tablets， while the observation group received Toludesvenlafaxine Hydrochloride Sustained-Release Tablets，with an 8-week continuous treatment course.To compare t he clinical total effective rate， anhedonia remission rate，the severity of depressive symptoms，degree of anhedonia，cognitive function，social function and quality of life between the two groups before and after treatment， the incidence of adverse reactions during treatment was recorded simultaneously. RESULTS After treatment，the total effective rate and anhedonia remission rate of the observation group were significantly higher than the control group （ P ＜0.05）. At the 4th and 8th weeks of treatment， the scores of Snaith-Hamilton Pleasure Scale， Hamilton Depression Rating Scale-17 Items， and Sheehan Disability Scale of both groups were significantly lower than those before treatment in the same group， and the observation group was significantly lower than the control group （ P ＜0.05）； the scores of Montreal Cognitive Assessment and Quality of Life Enjoyment and Satisfaction Questionnaire-Short Form were significantly higher than those before treatment in the same group， and the observation group was significantly higher than the control group （ P ＜0.05）. There was no statistically significant difference in the overall incidence of adverse reactions between the two groups （ P ＞0.05）. CONCLUSIONS Toludesvenlafaxine can significantly improve depressive symptoms， cognitive function， and social function in MDD patients with anhedonia，with good safety.

AIM: To explore the factors influencing the efficacy of diabetic macular edema(DME)with conbercept and to construct a nomogram prediction model. METHODS:Retrospective analysis. Patients with DME admitted from January 2021 to October 2025 were selected. All patients received intravitreal conbercept injection once monthly for three consecutive months. Subjects were divided into a good response group and a poor response group according to the reduction in central macular thickness(CMT)at 3 mo after treatment. The clinical data of the patients were collected to analyze factors associated with poor response to conbercept therapy in patients with DME, and to construct a nomogram prediction model for identifying poor responders to conbercept treatment among DME patients.RESULTS:A total of 400 DME patients(400 eyes)were included in this study. The response group consisted of 312 patients(312 eyes), with 200 males and 112 females, with an average age of 64.85±5.13 y. The non-response group consisted of 88 patients(88 eyes), with 54 males and 34 females, with an average age of 65.14±4.93 y. There were no differences between the two groups in terms of gender, age, alcohol consumption, smoking status, duration of diabetes, edema classification, disease classification, low-density lipoprotein, HRF, ELM and/or EZ continuity interruption, and SRF(all P>0.05). However, there were differences in DR disease duration, pre-treatment BCVA, high-density lipoprotein, glycated hemoglobin, DRIL, and VMIA(all P<0.05). Multivariate Logistic regression analysis showed that DR disease duration ≥1 y(OR=2.351, 95%CI: 1.360-4.065), poor pre-treatment BCVA(OR=3.432, 95%CI: 1.581-6.988), high glycated hemoglobin(OR=1.656, 95%CI: 1.346-2.038), presence of DRIL(OR=3.115, 95%CI: 1.532-6.333), and presence of VMIA(OR=2.526, 95%CI: 1.445-4.415)were all risk factors for poor response to conbercept treatment in DME patients, while elevated high-density lipoprotein(OR=0.025, 95%CI: 0.004-0.163)was a protective factor for poor response to conbercept treatment in DME patients(P<0.05). ROC analysis showed that the area under the curve(AUC)of the nomogram model for predicting poor response to conbercept treatment in DME patients was 0.817(95%CI: 0.776-0.854), with a sensitivity of 73.86% and a specificity of 78.21%. When the threshold probability was >3%, the nomogram model for predicting poor response to conbercept treatment in DME patients was more favorable for all patient treatment plans. CONCLUSION:The nomogram prediction model constructed in this study is helpful for the clinical early identification of patients with DME who have a high risk of poor response to conbercept treatment, and can provide a reference for the early prevention of poor response to conbercept treatment.

ObjectiveTo analyze the changes in infectious disease reporting timeliness before and after the implementation of the National Infectious Disease Intelligent Surveillance and Early Warning Pre-position Software (hereinafter referred to as “the pre-position software”) at Baoding Maternal and Child Health Hospital, and to evaluate its effectiveness in shortening reporting time and improving reporting timeliness. MethodsCase data of infectious diseases submitted by Baoding Maternal and Child Health Hospital to the National Disease Prevention and Control System during January to July 2024 (pre-implementation) and January to July 2025 (post-implementation) were selected. Overall differences in reporting timeliness between the two periods were compared, and stratified comparative analyses were performed by month, weekdays versus weekends/holidays, disease type, and population characteristics. ResultsBefore and after the implementation of the pre-position software, the hospital reported 623 and 587 infectious disease cases, respectively. Among the total 1 210 cases, 49.26% (596/1 210) had a reporting timeliness of <10 h. The highest number of reported cases fell into the 1 to <5 h range, accounting for 31.24% (378/1 210). There was a statistically significant difference in the composition of reported cases by reporting timeliness for infectious diseases in the hospital before and after the use of the pre-position software (χ²=27.38, P<0.001). Compared with January to July 2024, the median reporting timeliness in January to July 2025 was shortened by 3.77 h, and the difference was statistically significant (Z=-3.50, P<0.001). In April (the fourth month after implementation), the median reporting timeliness was shortened by 9.00 h (Z=-3.17, P=0.002). On non-working days (Saturdays and Sundays), it was shortened by 7.64 h (Z=-5.69, P<0.001), and on public holidays, it was shortened by 7.21 h (Z=-3.71, P<0.001). For class C infectious diseases, the median time was shortened by 3.49 h (Z=-3.05, P=0.002). For scattered children, it was shortened by 4.95 h (Z=-3.78, P<0.001). All differences were statistically significant. ConclusionAfter the implementation of the pre-position software, the reporting timeliness for infectious diseases at Baoding Maternal and Child Health Hospital is shortened, with particularly notable reductions observed in April, on non-working days, for Class C infectious diseases, and for scattered children, indicating the reporting timeliness is improved. This study provides empirical references for the promotion and application of this software in medical institutions.

The JAK2 V617F mutation is a key molecular event in myeloproliferative neoplasms and is strongly associated with an increased risk of thrombosis. This review aims to summarize the underlying mechanisms, clinical manifestations, and management strategies for thrombosis driven by the JAK2 V617F mutation. Relevant recent studies are analyzed to evaluate the effect of the mutation on molecular signaling, hematopoietic cell function, inflammatory activation, endothelial injury, and coagulation imbalance. Findings indicate that the JAK2 V617F mutation induces the persistent activation of the JAK-STAT pathway, leading to erythroid clonal expansion, platelet hyperreactivity, and enhanced neutrophil chemotaxis, along with excessive inflammatory cytokine release, NET formation, and platelet-leukocyte aggregation. These processes collectively promote endothelial dysfunction and hypercoagulation, ultimately contributing to arterial and venous thrombosis. Clinically, affected patients may present with coronary artery events deep vein thrombosis, and portal vein thrombosis, often accompanied by high recurrence rates and poor outcomes. In conclusion, the JAK2 V617F mutation drives thrombosis via multiple intertwined mechanisms, suggesting that future therapeutic strategies should integrate anticoagulation, anti-inflammation therapy, NET inhibition, and targeted JAK-STAT pathway blockade to improve patient survival.

BackgroundPatients with colorectal cancer are frequently comorbid with depression， which severely affects the quality of life and treatment compliance， while compromising the efficacy of anticancer treament and prognosis. Current therapeutic strategies still have notable limitations， particularly the lack of systematic and targeted synergistic regimens that integrate oncological management and anti-depressive intervention. It is of great clinical significance to explore a safe and effective new comprehensive intervention protocol and clarify its underlying mechanism of action. ObjectiveTo explore the effectiveness and safety of Shugan Yunpi Decoction in alleviating depressive and anxiety symptoms in colorectal cancer patients with depressive disorder through the PI3K-AKT signaling pathway， in order to provide references for the comprehensive treatment of colorectal cancer and depressive disorder. MethodsThis study was a randomized controlled trial. A total of 106 patients admitted to the Baoding No.1 Hospital of traditional Chinese medicine from November 2023 to July 2025 were enrolled， who met the diagnostic criteria for the Chinese protocol of diagnosis and treatment of colorectal cancer （2023 edition） and the diagnostic criteria for depressive disorder as specified in the Chinese Classification and Diagnostic Criteria of Mental Disease， third edition （CCMD-3）. Patients were divided into the study group and the control group using a random number table， with 53 cases in each group. The control group received conventional chemotherapy combined with traditional Chinese medicine five-element music therapy， while the study group received conventional chemotherapy combined with Shugan Yunpi Decoction therapy. Both groups were treated for 8 weeks. Depressive and anxiety symptoms were assessed using the Hamilton Depression Scale-17 item（HAMD-17） and Hamilton Anxiety Scale （HAMA）， respectively. Western blot protein immunoblotting was used to detect the expression levels of PI3K， AKT， and pAKT. Real-time fluorescence quantitative reverse transcription polymerase chain reaction （qRT-PCR） was used to detect the expression levels of PI3K mRNA and AKT mRNA. Adverse reactions were recorded using a self-designed adverse reaction record form. ResultsRepeated measures analysis of variance showed that the time effects （F=139.336， 234.747）， group effects （F=43.900， 101.266）， and time-group interaction effects （F=13.409， 43.216） for HAMD-17 and HAMA scores in both groups were statistically significant （P<0.01）. After 4 and 8 weeks of treatment， the HAMD-17 and HAMA scores in both groups were lower than those before treatment， with statistically significant differences （P<0.05）. HAMD-17 and HAMA scores in the study group were lower than those in the control group （P<0.05）. The time effects （F=571.356， 309.266， 414.492）， group effects （F=6.901， 26.361， 39.362）， and time-group interaction effects （F=18.592， 19.266， 33.484） for the protein expression levels of PI3K， AKT， and pAKT in both groups were all statistically significant （P<0.01）. After 8 weeks of treatment， the protein expression levels of PI3K and pAKT in the study group were lower than those in the control group， while the AKT protein expression level was higher than that in the control group（P<0.01）. The time effects （F=338.555， 225.059）， group effects （F=5.429， 9.726）， and time-group interaction effects （F=12.953， 21.214） for PI3K mRNA and AKT mRNA expression levels in two groups were all statistically significant （P<0.01）. After 8 weeks of treatment， the expression levels of PI3K mRNA and AKT mRNA in the study group were lower than those in the control group （P<0.05）. The incidence of adverse reactions in the study group was lower than that in the control group （χ²=4.810， P<0.05）. ConclusionShugan Yunpi Decoction may help to ameliorate depressive and anxiety symptoms in colorectal cancer patients with depressive disorder by regulating the PI3K-AKT signaling pathway， decreasing the levels of PI3K， pAKT， PI3K mRNA， and AKT mRNA， with a favorable safety profile. ［Funded by Baoding City Science and Technology Planning Project （number， 2341ZF291）］

Periampullary carcinoma is a malignant tumor of the biliopancreatic system originating from the ampulla of Vater， with the main pathological subtypes of intestinal-type and pancreatobiliary-type adenocarcinoma. Primary periampullary squamous cell carcinoma is relatively rare in clinical practice， with great difficulties in preoperative diagnosis and a lack of clinical experience and standardized diagnosis and treatment regimens. This article reports a case of primary periampullary squamous cell carcinoma in a male patient aged 55 years. The patient was admitted due to cutaneous and scleral jaundice for 2 weeks. Laboratory examination revealed obstructive jaundice， impaired liver function， and an increase in carbohydrate antigen 19-9， and radiological examination showed obstruction of the distal common bile duct and a space-occupying lesion in the ampullary region， leading to a preliminary clinical diagnosis of periampullary carcinoma of Vater. After admission， endoscopic retrograde cholangiopancreatography was first performed to relieve obstructive jaundice， and then biopsy of the ampullary lesion was conducted， with pathological findings highly suspicious for malignancy. Radical pancreaticoduodenectomy was performed after improvement in liver function， and postoperative pathology confirmed the diagnosis of moderately differentiated squamous cell carcinoma of the ampulla. PET-CT reexamination on day 52 after surgery showed well-healed surgical anastomosis and multiple hypermetabolic nodules in the right hepatic lobe， which could not rule out tumor metastasis. This case report can provide a reference for improving awareness of this rare disease and optimizing related diagnosis and treatment decisions in clinical practice.