ObjectiveThe malaria parasites remodel the host erythrocyte structure by exporting parasite proteins that interact with the membrane skeleton proteins of red blood cells (RBCs), facilitating their intracellular survival and pathogenicity. Skeleton-binding protein 1 (SBP1) is a conserved exported protein across Plasmodium species. In Plasmodium falciparum, SBP1 has been reported to interact with erythrocyte membrane skeleton proteins 4.1R and spectrin, while its contribution to erythrocyte remodeling and parasite virulence in Plasmodium berghei (Pb) remains unclear. This study aims to determine whether PbSBP1 associates with the host cytoskeletal protein 4.1R and to investigate its role in the remodeling of host RBCs and the pathogenicity of Plasmodium berghei. MethodsIn Plasmodium berghei, the relationship between PbSBP1 and the erythrocyte cytoskeletal protein 4.1R was examined using co-immunoprecipitation. A Pbsbp1 gene knockout mutant of Plasmodium berghei (Pbsbp1∆) was generated based on the principle of double crossover homologous recombination. The deformability of erythrocytes infected with Pbsbp1∆ parasites was assessed using microfluidic methods. Microchannels with an array of cylindrical pillars were used to detect modifications in infected RBC deformability. The infected RBCs were squashed between the rows and recovered between the columns and the transit velocity (μm/s) of infected RBCs travelling through the microchannel was recorded. The component of the erythrocyte membrane skeleton junctional complex, tropomodulin (TMOD), was fluorescently labeled, and the cytoskeletal network of infected erythrocytes was imaged using super-resolution stochastic optical reconstruction microscopy (STORM) to analyze ultrastructural changes in the cytoskeleton of wild-type (WT) and Pbsbp1∆-infected erythrocytes. Actin-based junctional complexes were displayed as individual clusters by the labeled TMOD in the STORM images, and the cluster densities and distances between adjacent clusters of infected RBCs were calculated. Additionally, rodent malaria models (BALB/c mice) and experimental cerebral malaria models (C57BL/6 mice) were employed to monitor the growth of Pbsbp1∆ and WT parasites during the intraerythrocytic stage and their capacity to induce cerebral malaria in mice. ResultsPbSBP1 may participate in the remodeling of infected erythrocytes through direct or indirect interaction with the erythrocyte cytoskeletal protein 4.1R. Microfluidic assays revealed that the deformability of erythrocytes infected with Pbsbp1∆ parasites was significantly enhanced compared to those infected with WT parasites. STORM imaging further demonstrated that the ultrastructure of the erythrocyte cytoskeleton in Pbsbp1∆-infected cells was altered relative to that in WT-infected erythrocytes. The distances between nearest neighbors of clusters had a tendency to increase while the cluster densities were decreased in Pbsbp1∆-infected RBCs compared to WT-infected RBCs. Subsequent phenotypic analysis indicated that the growth rate of Pbsbp1∆ parasites during the intraerythrocytic stage was significantly slower than that of WT parasites, and their ability to induce cerebral malaria in mice was also attenuated. These findings suggest that PbSBP1 is involved in the remodeling of the erythrocyte membrane skeleton, likely through its direct or indirect interaction with protein 4.1R, thereby regulating the deformability of infected erythrocytes and influencing the pathogenicity of the blood-stage parasites. ConclusionThis study establishes a role for PbSBP1 in host erythrocyte remodeling and parasite virulence, providing new research strategies for the prevention and treatment of malaria.

Ultrasonic bone-cutting instruments have gained traction in open and minimally invasive spine surgery because of their selective bone-cutting capability while preserving adjacent soft-tissue structures. However, their use in uniportal endoscopic spine surgery has not been reported in the peer-reviewed literature. This technical note describes a uniportal endoscopic surgical technique that uses an ultrasonic osteotome for uniportal endoscopic lumbar interbody fusion (U-ELIF) and reports preliminary outcomes. Specifically, we describe the technical nuances of ultrasonic osteotome use in U-ELIF and evaluate its feasibility and safety, with an emphasis on minimizing complications.

This study elucidated the structure-activity relationships (SAR) of three distinct opioid ligand series at the μ-opioid receptor (μ-OR) and investigated the ligand-dependent role of arrestin in downstream signaling. Radioligand binding assays across 13 compounds revealed that high-affinity μ-OR binding is not restricted to a single chemical scaffold. For fentanyl analogs, SAR analysis identified four key structural determinants: the N-phenethyl group (R1) is essential for μ-OR binding, the piperidine 4-position (R2) is sterically constrained and tolerates only small substituents such as carbomethoxy, the acyl side chain (R3) tolerates diverse chemical modifications including alkyl, alkoxy, and heteroaryl groups without substantial loss of affinity, and para-substitution on the phenethyl ring (R4) with electron-withdrawing groups like fluorine is well-tolerated. Analysis of non-fentanyl scaffolds (2-Methyl AP-237, W-15, and brorphine) demonstrated that specific side-chain functionalization, rather than core scaffold architecture, primarily determines binding potency. Comparison of classical opioids further revealed that structural flexibility, exemplified by methadone, can confer superior binding affinity compared to the rigid morphine scaffold. Consistent with this structural diversity, the contribution of arrestins to ERK activation varied substantially across compounds, suggesting that μ-OR-biased signaling is not dictated exclusively by intrinsic receptor properties but emerges from the interplay between receptor conformation and ligandspecific structural features. Collectively, our results provide a molecular framework for understanding opioid pharmacology with important implications for rational drug design aimed at minimizing adverse effects while maintaining analgesic efficacy.

Objective: The present study made a retrospective analysis aiming to report chiggers on small mammals (hosts) in Jinping County on the China-Vietnam border, Yunnan of southwest China. Methods: The indexes of chigger infestation and chigger community were routinely calculated. The niche width and overlap were calculated for analyzing chiggers’ host selection. The sample completeness was determined through coverage index (CI). Results: A total of 7,718 chiggers from 274 small mammal hosts were identified as 52 species, 10 genera, three subfamilies and two families, including nine vector species. The CI of chigger species reached 99.84%. The genus Leptotrombidium accounted for 94.86% of 10 chigger genera. The majority of chiggers (constituent ratio [C r ] = 95.35%) came from rodents (Rodentia). The four dominant chigger species (C r = 89.88%, 6,937/7,718) included Leptotrombidium deliense, the most important vector of scrub typhus in China. Conclusions and Relevance: The abundant L. deliense in Jinping, together with other vector chigger species and their low host specificity, increases the potential transmission risk of scrub typhus in China-Vietnam border areas.

Definitive chemoradiotherapy (dCRT) has become a cornerstone in the treatment of locally advanced esophageal cancer; however, local control remains suboptimal, and persistent lesions or locoregional recurrences after treatment are not uncommon. For patients without distant metastases but with local failure, whether surgical intervention can still offer curative potential remains a major clinical dilemma. Salvage esophagectomy (SE) offers potential long-term survival for selected patients, but this procedure is performed in the context of severe fibrosis, impaired local blood supply, and obscured anatomical planes following chemoradiotherapy, resulting in significantly higher perioperative risk compared to primary esophagectomy. Consequently, controversies exist regarding patient selection, preoperative restaging, choice of surgical approach, extent of lymphadenectomy, gastrointestinal reconstruction, and perioperative management. In recent years, with the refinement of restaging modalities such as PET/CT, the accumulation of experience in high-volume centers, and emerging evidence from clinical studies, the clinical role of SE has gradually shifted from a "high-risk salvage measure" to a "selective curative strategy aimed at achieving long-term survival in carefully selected patients". Nevertheless, standardized guidelines for patient selection, technical approaches, and perioperative management are still lacking. Based on current evidence and clinical experience, experts organized by the Integrated Esophageal Cancer Committee of Chinese Anti-Cancer Association systematically reviewed key issues regarding SE, including its definition, indications, preoperative evaluation, choice of surgical approach, lymphadenectomy, gastrointestinal reconstruction, and perioperative management, and formulated a Chinese expert consensus. This consensus aims to provide guidance for standardized assessment, appropriate referral, individualized surgical decision-making, and optimized perioperative management of patients with locoregional failure after dCRT. Ultimately, this will increase the likelihood of R0 resection, reduce the risk of severe complications, and promote the safer, more judicious, and standardized implementation of SE in high-risk scenarios.

Tumor metastasis is the leading cause of high mortality in most cancers, and numerous studies have demonstrated that the malignant crosstalk of multiple components in the tumor microenvironment (TME) together promotes tumor metastasis. Cancer-associated fibroblasts (CAFs) are the major stromal cells and crosstalk centers in the TME of various kinds of tumors, such as breast cancer, pancreatic cancer, and prostate cancer. Recently, the CAF-induced pro-tumor metastatic TME has gained wide attention, being considered as one of the effective targets for tumor therapy. With in-depth research, CAFs have been found to promote tumor metastasis through multiple mechanisms, such as inducing epithelial-mesenchymal transition in tumor cells, remodeling the extracellular matrix, protecting circulating tumor cells, and facilitating the formation of a pre-metastatic niche. To enhance the anti-tumor metastasis effect, therapeutic strategies designed by combining nano-drug delivery systems with CAF modulation are undoubtedly a desirable choice, as evidenced by the research over the past decades. Herein, we introduce the physiological properties of CAFs, detail the possible mechanisms whereby CAFs promote tumor metastasis, categorize CAFs-based nano-drug delivery strategies according to their anti-metastasis functions and discuss the current challenges, possible solutions, as well as the future directions in order to provide a theoretical basis and reference for the utilization of CAFs-based nano-drug delivery strategies to promote tumor metastasis therapy.

Objective:To analyze the characteristics and general patterns of adverse drug reactions associated with aripiprazole, and to identify potential risk signals, thereby providing references for the safe and rational use of medications in clinical practice.Methods:This is a descriptive study that collected and summarized reports of adverse reactions to aripiprazole submitted by medical institutions in Anhui Province to the National Center for Adverse Drug Reaction Monitoring, China from January 2019 to December 2024. The basic characteristics of patients, the treatment regimens used, the timing of adverse drug reaction occurrence, the clinical manifestations of the affected systems, and the outcomes of these adverse drug reactions were statistically analyzed to identify the clinical characteristics and risk factors of adverse drug reactions associated with aripiprazole.Results:A total of 1 106 adverse reaction case reports related to aripiprazole were collected, with a male-to-female ratio of 1:1.29 ( χ2 = 8.64, P = 0.003) and an average age of (35 ± 16) years. The primary diseases treated included schizophrenia (768 cases, 69.44%), bipolar affective disorder (96 cases, 8.68%), and depressive disorder (75 cases, 6.78%). Adverse reactions occurred within the first 2 weeks of medication in 689 cases (62.29%). All medications were oral formulations, with 978 cases (88.43%) falling within the recommended daily dose range of 10-30 mg/d, while 15 cases (1.36%) exceeding the maximum recommended dose of 30 mg/d. The most common clinical manifestations were related to the nervous system (696 cases, 62.93%), followed by cardiovascular system manifestations (146 cases, 13.20%). The majority of adverse reactions showed improvement or recovery (1 052 cases, 95.12%). Conclusions:Aripiprazole is widely used in clinical practice, and the occurrence of adverse reactions is correlated with patient characteristics and treatment regimens. It is advisable to enhance the rational clinical use and monitoring of aripiprazole. Such measures will aid in preventing or reducing the occurrence of severe adverse reactions.

Hypothermia is a clinical syndrome characterized by core body temperature<35℃,caused by significant heat loss from body surface in cold environment.As a systemic cold injury,it can be lethal if treatment is delayed.Emergent diagnosis and treatment of hypothermia are expected to improve the prognosis of patients.In 2005,the U.S.Army Research Institute of Environmental Medicine(USARIEM)issued guidelines for the prevention and management of cold injuries,but there has been no corresponding standard in China.Therefore,Emergency Branch of Chinese Medical Rescue Association,Emergency Medical Equipment Society of China Association of Medical Equipment,Integrated Rehabilitation Medical Branch of Chinese Medical Rescue Association,and Pre-Hospital Emergency Care Working Committee of Chinese Aging Well Association jointly developed the Chinese Expert Consensus on Emergent Treatment of Hypothermia(2025 edition).The consensus covers the pathophysiology,etiology and epidemiology,diagnosis and severity grading,prehospital treatment,and in-hospital treatment of hypothermia,including 15 recommendations in total,aiming to provide guidance for the relevant clinical rescue work.

Objective:To investigate how gut microbiota changes during prostate cancer radiotherapy and decipher the relationship of gut microbiota with disease progression and chronic radiation enteritis.Methods:Thirty-one patients with prostate cancer were included in this study,admitted to The First Affiliated Hospital of Xinjiang Medical University from September 2022 to December 2023.The clinical data and stool samples of the patients were collected,and patients were followed up.The collected stool specimens were subjected to 16S rRNA se-quencing to detect gut microbiota and bioinformatics analysis.Results:The relative abundance of phyla such as Firmicutes and Actinobac-teria increased,and that of Bacteroidetes decreased(P<0.05)with an increasing radiotherapeutic dose,while beta diversity was significantly higher(P=0.001).The relative abundance of the phylum Actinobacteria was significantly higher in the prostate cancer progression group than in the non-progression group(P<0.05),the relative abundances of genera such as Sutterella and Haemophilus were significantly higher in the progression group(P<0.05).That of Verrucomicrobia and its offshoots in Akkermansia was higher in the chronic radiation enteritis than in the non-enteritis group(P<0.05),while the relative abundances of Coprococcus_1 and Catabacter in the non-enteritis group were higher than those in the enteritis group(P<0.05).Conclusions:Radiotherapy dose accumulation significantly remodeled the floral structure.Sutterella and Haemophilus of the phylum Proteobacteria might be key flora in prostate cancer recurring early after treatment.An augmen-ted abundance of Akkermansia might increase the risk of chronic radiation enteritis,whereas the flora under the Lachnospiraceae branch might exert aprotective effect against chronic radiation enteritis.

Objective To evaluate the clinical effectiveness and safety of different traditional Chinese medicine(TCM)prescriptions combined with conventional western drugs to improve idiopathic membranous nephropathy(IMN)based on the Chinese medicine evidence system.Methods A computerized search of databases was conducted to collect randomized controlled trials(RCTs)of TCM compound formulas combined with conventional western medicines for the treatment of IMN,with a search timeframe from the establishment of the database to October 2023.Thirty-five RCTs involving six interventions and containing 2518 IMN patients were finally included.The quality of the included literature was evaluated.Reticulated Meta-analysis was performed,and surface under the cumulative ranking(SUCRA)curve was used to rank the clinical efficacy and safety of the six interventions,aiming to provide an evidence-based basis for the rational clinical selection of prescriptions for treating patients with IMN.Results The formula of tonifying deficiency and eliminating stasis combined with conventional western medicine showed significant effects in lowering 24-hour urine protein quantification(SUCRA=95.3％)and total cholesterol level(SUCRA=98.2％).The formula of tonifying deficiency,eliminating stasis,purging heat,and dispelling dampness combined with conventional western medicine was effective in lowering blood creatinine(SUCRA=80.4％)and increasing serum albumin level(SUCRA=72.9％).The formula of tonifying deficiency and clearing heat and dampness combined with conventional western medicine was more effective in lowering M-type phospholipase A2 receptor antibody titer(SUCRA=86.0％).Conclusion In terms of safety,the adverse effects of the TCM compound formula combined with conventional western drugs were overall less than those of conventional western drugs alone.