Tianjin People's Hospital

Recombinant human erythropoietin (rhEPO) fused with human immunoglobulin G (IgG) Fc fragment (rhEPO-Fc) is a novel erythropoiesis-stimulating agent designed to extend plasma half-life and enhance biological activity. However, data on the efficacy and safety of rhEPO-Fc in hemodialysis patients with chronic kidney disease (CKD)-related anemia remain limited. This phase 3 trial enrolled patients from 45 Chinese hospitals. Participants were randomized (2:1) to receive either rhEPO-Fc or rhEPO (Chinese hamster ovary cell-derived) for 28 weeks. The rhEPO-Fc responders were eligible for a 24-week extension period. The primary endpoint was the least square mean (LSM) change in hemoglobin (Hb) levels from baseline between weeks 21 and 28. Among 356 rhEPO-Fc and 178 rhEPO recipients, patients receiving rhEPO-Fc demonstrated non-inferiority Hb maintenance compared with rhEPO. The inter-group LSM differences in the full analysis set and per-protocol set were 3.96 g/L (95% CI: 3.02–4.89; p < 0.001) and 2.27 g/L (95% CI: 0.60–3.95; p = 0.008), respectively. Adverse drug reaction rates were comparable (rhEPO-Fc: 39.2% vs. rhEPO: 40.2%). Dose adjustments due to treatment-emergent adverse events were significantly lower with rhEPO-Fc (0.0% vs. 2.2%; p < 0.05). Deaths unrelated to the study drugs occurred in two rhEPO-Fc and four rhEPO patients. These findings indicated that rhEPO-Fc effectively maintained Hb levels in patients with CKD anemia undergoing hemodialysis, showing comparable efficacy to rhEPO with reduced dosing frequency and a similar safety profile.

We have carefully reviewed the comments and appreciate the thoughtful feedback provided by the readers.Below, we have prepared a point-by-point response to address the concerns raised. Response to the Letter Dose Selection and Correction of Ulinastatin (UTI) Dosage ErrorWe fully acknowledge the comment regarding the reported UTI dosage.The value "30 IU" was indeed an error; the correct dosage is 300,000 IU.This inaccuracy resulted from a unit conversion oversight during manuscript preparation (omission of the term " " [ten-thousand]).We sincerely apologize for this error and will correct it promptly in the final revised manuscript. Rationale for Dose Selection: The single preoperative dose of 300,000 IU was selected based on established clinical practice and pharmacological studies.Multiple references indicate that the commonly used clinical dosage of UTI ranges between 100,000 and 500,000 IU (or 10,000 U/kg). 1-4Furthermore, preclinical studies using a rat incisional pain model demonstrated that a single preoperative dose within this range effectively reduced postoperative mechanical hypersensitivity. 5Our own pilot data confirmed that this dosage offered an optimal balance between efficacy and safety. Future Refinement: We agree with the suggestion to include multiple dosing groups (eg, 100,000 IU, 300,000 IU, 500,000 IU) in future trials to identify the optimal regimen.Additionally, incorporating pharmacokinetic data (eg, plasma concentration-time curves) would further substantiate dose justification.

Fecal incontinence is a refractory disease.The main clinical manifestation is that patients cannot control the discharge of gas, solid or liquid feces in the rectum autonomously. It significantly compromises patients'quality of life and imposes substantial economic burdens on both families and the healthcare system. With the evolution of therapeutic paradigms and innovations in diagnosis and treatment modalities, the management approach for fecal incontinence has progressively evolved:early strategies centered on anatomical reconstruction, following the advent of sacral nerve modulation, the focus transitioned to the restoration of physiological function;and since the turn of the 21st century ,emphasis has been placed on comprehensive evaluation and stratified therapy, leading to the establishment of a precision-oriented and patient-tailored diagnostic and therapeutic framework.This paper examines the accumulation of evidence-based medical data and the drivers behind these shifts in treatment models to elucidate the underlying patterns in the management of FI. It also addresses current controversies, such as screening for asymptomatic anal sphincter defects and gaps in psychological support, proposing targeted solutions and stratified care pathways to inform clinical practice and future research.

The cervical spine, a critical junction between the head and torso, is a rare but significant site for both primary and metastatic tumors. While primary tumors of the cervical spine are uncommon, certain types, such as chordomas and giant cell tumors, are particularly notable for their potential to affect this region. Metastatic lesions, although more frequent, present unique diagnostic and therapeutic challenges due to the complex anatomy of the cervical spine. Imaging is indispensable for the evaluation of cervical spine tumors, serving as the foundation for diagnosis, treatment planning, and monitoring therapeutic outcomes. Radiography, CT and MRI are the primary modalities used to assess tumor morphology, extent and relationship to surrounding structures. However, imaging alone may not always yield a definitive diagnosis, as some tumors lack distinctive features. Nevertheless, a combination of clinical presentation, epidemiological factors, and imaging findings often enables radiologists and clinicians to narrow the differential diagnosis and guide further management. Precise imaging interpretation is essential to prevent devastating clinical consequences resulting from diagnostic error, such as irreversible neurological damage, avoidable death, and significant long-term disability. This review provides a comprehensive overview of tumors that can involve the cervical spine, emphasizing their clinical and imaging characteristics. By highlighting key diagnostic features and discussing the latest advancements in imaging technology, aims to enable physicians in radiology, pathology, and clinical departments to gain a more comprehensive understanding of the imaging, pathological, and clinical characteristics of cervical spine tumors, thereby reducing misdiagnosis rates and alleviating the burden on patients.

PurposeTo explore the biomechanical properties of Zimmer natural nail (ZNN) and proximal femoral nail antirotation (PFNA)-II nails in treating older patients with unstable intertrochanteric fractures, thereby guiding the selection of internal fixation devices in clinical practice.MethodZNN and PFNA fixation models for unstable intertrochanteric fractures (AO type 31-A2.2) were established using the three-dimensional finite element method and in vitro mechanical experiments, respectively. We compared the Von Mises stress distribution, peak stress, implants and femur locations, displacement distribution, maximum displacement, location of the models, and maximum crack distance at the fracture ends between the two groups. Additionally, we compared the axial stiffness, femoral head axial displacement, and failure load for both groups.ResultFinite element analysis for AO type 31-A2.2 unstable intertrochanteric fractures showed that stresses in the ZNN and PFNA-II models concentrated at the distal locking screws, with maximum Von Mises stresses of 373.2 MPa and 811.5 MPa, respectively. The femoral stress concentrated at the distal locking screw perforation hole, with maximum Von Mises stresses of 186.5 MPa for ZNN and 1602.0 MPa for PFNA-II. According to the displacement distribution cloud map, the maximum displacements of the ZNN and PFNA-II models were 3.768 mm and 3.757 mm, respectively, both at the top of the femoral head. The maximum crack distances in the ZNN and PFNA-II models were 0.16 mm and 0.14 mm, respectively. The maximum displacements and crack distances at the fracture end were similar for both models. Biomechanical tests revealed that the axial stiffness in the ZNN group was greater than that in the PFNA-II group, with averages of 299.67 ± 27.00 N/mm and 269. 6 ± 15. 24 N/mm, respectively; the difference between the two groups was significant (T = 2. 375, P = 0. 039). In the cyclic loading test, the average axial displacement of the femoral head was 0.62 ± 0.22 mm in the ZNN group and 0.59 ± 0.23 mm in the PFNA-II group, with no significant differences (t = 0. 155, P = 0. 880). The failure load of the ZNN group significantly exceeded that of the PFNA-II group, with average failure loads of 3.95 ± 0.07 kN and 3.54 ± 0. 15 kN, respectively (t = 6.207, P < 0.001).ConclusionIn AO type 31-A2.2 unstable intertrochanteric fractures, the biomechanical properties of the ZNN group were superior to those of the PFNA-II group in terms of axial stiffness and failure load. In the cyclic loading test, the axial displacement of the femoral head was similar in both groups. The finite element analysis showed a more favorable mechanical distribution for the ZNN group. The ZNN implant demonstrated favorable biomechanical characteristics under the specific experimental conditions tested in this study.

BackgroundParoxysmal nocturnal haemoglobinuria (PNH) is an acquired clonal haematopoietic stem cell disorder. Immune escape is crucial in PNH, and our previous studies revealed that natural killer (NK) cells potential participate in the immune escape of PNH. This study aimed to investigate the subtypes and functional changes of NK cells in PNH patients.MethodsWe analysed CD59+ and CD59− bone marrow mononuclear cells using single‐cell RNA sequencing (scRNA‐seq). The results were validated through flow cytometry and co‐culture experiments.ResultsWe classified NK cells into seven subtypes by scRNA‐seq, and found significant differences in the distribution of subtypes in CD59+ and CD59− NK cell of PNH patients. Compared with controls, the proportion of active and adaptive NK cells was higher in CD59+ NK cells. Conversely, the proportion of CD56bright NK cells and terminal NK cells was elevated in CD59− NK cells. Additionally, the proportion of mature NK cells decreased in both the CD59+ and CD59− groups. Gene ontology and Kyoto Encyclopedia of Genes and Genomes analysis revealed impaired function of CD59− NK cells, whereas CD59+ NK cells showed minimal change. Furthermore, similar results were verified by flow cytometry and co‐culture in vivo and in vitro. And the proportion of NK cells was closely related to the proportion of CD8+ T cells and the clinical indicators of disease.ConclusionsThe quantity and function of NK cells in PNH patients are insufficient, in which CD59− NK cells have functional defects, whereas CD59+ NK cells were mainly activated and potential involved in immune escape by regulation of T cells.

BackgroundLinezolid-induced hyperlactatemia may be masked by metabolic alkalosis, creating diagnostic challenges. This case demonstrates how acid–base disturbances can delay toxicity recognition in geriatric patients.Case presentationAn 82-year-old Han Chinese woman with carbapenem-resistant Acinetobacter baumannii pneumonia developed severe hyperlactatemia (peak 17 mmol/L) during linezolid therapy (600 mg every 12 hours for 14 days). Despite progressive lactate elevation (1.6 → 17 mmol/L), alkalotic pH (7.45–7.51) and normal anion gap (8–12 mmol/L) obscured the diagnosis.InterventionsSerial monitoring included arterial blood gas analysis and serum lactate levels. Linezolid was discontinued upon recognition of hyperlactatemia. Continuous renal replacement therapy was initiated post-discontinuation.OutcomesA lactate/HCO3− ratio > 0.17 (day 20) preceded metabolic decompensation by 5 days. Renal replacement failed to correct lactate accumulation, suggesting irreversible mitochondrial damage.ConclusionpH-based monitoring inadequately detects linezolid toxicity in alkalotic patients. Lactate/HCO3− ratios (> 0.17) should be incorporated into geriatric antimicrobial protocols for early intervention.

Object recognition technology based on deep learning can effectively improve the perception ability of unmanned aerial vehicles (UAVs). However, this often requires more efficient and advanced algorithms to meet the precision requirements in practical applications. In this paper, we have studied the effective mechanisms for improving the performance of object recognition algorithms from the perspective of aerial photography. Specifically, we propose a new global attention calculation module named S_GAM and an efficient spatial pyramid pooling module called E_SPP. The S_GAM consists of a spatial attention calculation module and a channel attention calculation module. Multi-scale convolution is introduced in the spatial attention calculation, aiming to enhance the multi-scale feature extraction ability. The channel attention calculation part adopts the ECA (Efficient Channel Attention) architecture, which can effectively increase the diversity of feature extraction. The E_SPP module utilizes an efficient cascading architecture to achieve feature fusion. The training and testing of the model use the open-source dataset Visdrone2019. Through experimental comparison, the accuracy (mAP0.5) of SEM-YOLOv7 is improved by 2.6% compared with the benchmark YOLOv7 algorithm and by 4.7% compared with the YOLOv8 algorithm. When SEM-YOLOv7 is deployed on the RK3588 and optimized with multi-threading, the recognition frame rate is between 22 and 25 frames per second, which can meet the requirements of practical applications.