Bispecific killer cell engagers (BiKEs) are a powerful tool to incite the killing power of natural killer (NK) cells. Here, we posited that the BiKE technology could be utilized to deplete activated immune cells expressing programmed death-1 (PD-1⁺ cells), and hence treat autoimmune diseases since these cells drive the disorders. We designed and generated PD-1 BiKE that targets an activating NK cell receptor, CD16, and PD-1. PD-1 BiKE showed specific binding to PD-1⁺ cells and engaged CD16 simultaneously. PD-1 BiKE enhanced NK cell-mediated apoptosis and depletion of PD-1⁺ Raji cells, but not PD-1^- Raji cells. Further, PD-1 BiKE induced apoptosis of primary PD-1⁺ T lymphocytes that are highly relevant to autoimmune disease progression. The BiKE depleted 42% of primary T cells that were stimulated in vitro. Importantly, those ablated primary T cells were activated cells. Meanwhile, naive T cells were spared by the BiKE treatment, supporting the crucial selectivity of PD-1 BiKE-directed cell depletion. Lastly, PD-1 BiKE is more effective than a conventional depleting antibody in the depletion of PD-1⁺ cells. The current work supports PD-1 BiKE is a selective, potent, and safe tool to deplete PD-1⁺ cells.

Nonunion of osteoporotic vertebral fractures (OVF), predominantly affecting the elderly, can lead to intractable pain, vertebral collapse, progressive kyphotic deformity, and neurological impairment, significantly compromising patients′ quality of life. There exists considerable debate on diagnosis and management of OVF, encompassing key issues such as clinical diagnosis and staging criteria for nonunion, surgical indications and procedure selection, and postoperative rehabilitation planning. Currently, there lacks standardized clinical guideline and expert consensus on the diagnosis and management of OVF nonunion in China. To address this gap, Minimally Invasive Surgery Group of Chinese Orthopedic Association, Osteoporosis Committee of Chinese Association of Orthopedic Surgeons, Prevention and Rehabilitation Committee for Osteoporosis of Chinese Association of Rehabilitation Medicine and Minimally Invasive Orthopedic Surgery Branch of China Association for Geriatric Care jointly organized domestic experts in spinal surgery, endocrinology, and rehabilitation to formulate the Clinical guideline for the diagnosis and treatment for nonunion of osteoporotic vertebral fractures ( version 2025), based on existing literature and clinical experience and adhering to principles of scientific rigor and practicality. The guideline provided 13 evidence-based recommendations encompassing diagnosis and treatment of OVF nonunion, aiming to standardize its clinical management.

Nonunion of osteoporotic vertebral fractures (OVF), predominantly affecting the elderly, can lead to intractable pain, vertebral collapse, progressive kyphotic deformity, and neurological impairment, significantly compromising patients′ quality of life. There exists considerable debate on diagnosis and management of OVF, encompassing key issues such as clinical diagnosis and staging criteria for nonunion, surgical indications and procedure selection, and postoperative rehabilitation planning. Currently, there lacks standardized clinical guideline and expert consensus on the diagnosis and management of OVF nonunion in China. To address this gap, Minimally Invasive Surgery Group of Chinese Orthopedic Association, Osteoporosis Committee of Chinese Association of Orthopedic Surgeons, Prevention and Rehabilitation Committee for Osteoporosis of Chinese Association of Rehabilitation Medicine and Minimally Invasive Orthopedic Surgery Branch of China Association for Geriatric Care jointly organized domestic experts in spinal surgery, endocrinology, and rehabilitation to formulate the Clinical guideline for the diagnosis and treatment for nonunion of osteoporotic vertebral fractures ( version 2025), based on existing literature and clinical experience and adhering to principles of scientific rigor and practicality. The guideline provided 13 evidence-based recommendations encompassing diagnosis and treatment of OVF nonunion, aiming to standardize its clinical management.

Objective:To explore the influencing factors for low back pain after decompression and fusion in patients with lumbar spinal stenosis and to construct a Nomogram prediction model.Methods:A retrospective study was conducted to analyze the 132 patients with lumbar spinal stenosis who had been treated at Department of Orthopedics, Nanyang Central Hospital from May 2021 to March 2022. The patients were divided into 2 groups according to their visual analog scale (VAS) pain score: a back pain-free group (104 cases with VAS ≤ 2) and a back pain group (28 cases with VAS > 2). Univariate and multiple logistic regression analyses were employed to identify the influencing factors for occurrence of lower back pain and a Nomogram prediction model for the risk of lower back pain was constructed in patients with lumbar spinal stenosis after decompression and fusion. The accuracy of the model was assessed using the receiver operating characteristic (ROC) curve. Furthermore, the model accuracy was pre-tested using an external validation model which included 66 illegible patients with lumbar spinal stenosis treated at Department of Orthopedics, Nanyang Central Hospital from May 2022 to March 2023. A comparison was made between the outcomes predicted by the model and the actual outcomes observed. The fit of the model was evaluated through the Hosmer-Lemeshow test.Results:The results of the multifactorial analysis indicated that interleukin (IL-1 β), postoperative aseptic inflammation in the vertebral canal, and intraoperative blood loss were independent influencing factors for the occurrence of lower back pain (all P < 0.05). A risk Nomogram prediction model was thus established based on these factors. The area under the curve (AUC) was 0.975, the sensitivity 92.90%, the specificity 91.30%, and the Youden index 0.842. External validation of the model showed an overall accuracy of 99.80%. The Hosmer-Lemeshow test demonstrated good model fit ( χ2=3.512, P=0.898). Conclusions:IL-1 β, postoperative aseptic inflammation in the vertebral canal, and intraoperative blood loss may be the primary influencing factors for the occurrence of lower back pain in patients with lumbar spinal stenosis after decompression fusion surgery. The Nomogram prediction model based on these influencing factors demonstrates excellent predictive efficacy for lower back pain.

Objective:To investigate the clinical characteristics and risk factors of critical burn patients complicated with invasive fungal infection.Methods:A retrospective case series study was conducted. From January 2017 to December 2022, 88 critical burn patients combined with invasive fungal infection who met the inclusion criteria were admitted to Zhengzhou First People's Hospital, including 61 males and 27 females, aged 26-74 years. Data on invasive fungal infection sites and the detection of pathogens in patients were recorded. According to the survival outcome within 28 days after admission, the patients were divided into survival group (63 cases) and death group (25 cases). The following data of patients were compared between the two groups, including the basic data and injuries of patients at admission such as age, sex, body weight, total burn area, combination of inhalation injury, combination of hypertension and diabetes, acute physiology and chronic health status evaluation Ⅱ (APACHE Ⅱ) score, and admission time after burns, the levels of blood biochemical indexes within 24 h after admission such as white blood cell count, platelet count, red blood cell count, monocyte count, neutrophil count, lymphocyte count, alanine transaminase, aspartate transaminase, glucose, creatinine, urea nitrogen, D-dimer, galactomannan (GM), 1,3-β-D glucan, and creatine kinase, the application of invasive procedures and vasoactive drugs during the treatment such as continuous renal replacement therapy, ventilator-assisted breathing, tracheotomy, deep vein catheterization, skin grafting >2 times, the levels of infection indicators on post admission day (PAD) 1, 3, 7, and 14 including C-reactive protein (CRP), procalcitonin, lactic acid, interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α), and the detection of pathogens in the process of treatment. Data were statistically analyzed with independent sample t test, analysis of variance for repeated measurement, chi-square test, Mann-Whitney U test, and Bonferroni correction. Multivariate logistic regression analysis was performed to screen the independent risk factors that affected death of critical burn patients complicated with invasive fungal infection. Results:The main sites of invasive fungal infection were the wounds (67 cases) and blood stream (46 cases), with Candida fungi (58 strains) as the main strain for fungi infection, and there were a total of 30 cases of infection with mixed pathogenic bacteria. Compared with those in survival group, the APACHE Ⅱ score, proportions of combination with inhalation injury and hypertension of patients in death group were significantly increased ( t=2.11, with χ2 values of 6.26 and 9.48, respectively, P<0.05), while the other basic data and injury condition had no significant changes ( P>0.05). Compared with those in survival group, the levels of D-dimer, GM, and 1,3-β-D glucan of patients in death group were significantly increased within 24 h after admission (with t values of 2.42, 2.05, and 2.21, respectively, P<0.05), while the other blood biochemical indexes within 24 h after admission, as well as the proportions of applying invasive procedures and application of vasoactive drugs during the treatment process were not significantly changed ( P>0.05). The levels of infection indicators of patients on PAD 1 and 3 were similar between the two groups ( P>0.05). The procalcitonin level on PAD 7 and the levels of CRP, procalcitonin, lactic acid, IL-6, and TNF-α on PAD 14, as well as the proportion of infection with mixed pathogenic bacteria of patients in death group were significantly higher than those in survival group (with t values of 4.69, 3.89, 6.70, 6.14, 4.65, and 3.26, respectively, χ2=12.67, P<0.05). Multivariate logistic regression analysis showed that combination with inhalation injury, combination with hypertension, and infection with mixed pathogenic bacteria were independent risk factors for death of critical burn patients complicated with invasive fungal infection (with odds ratios of 5.98, 4.67, and 6.19, respectively, 95% confidence intervals of 1.42-15.39, 1.41-25.28, and 1.86-20.58, respectively, P<0.05). Conclusions:The main sites of infection in critical burn patients complicated with invasive fungal infection are the wounds and blood stream, with Candida fungi as the main strain for fungi infection, and a large proportion of infection with mixed pathogenic bacteria. The combined inhalation injury, combined hypertension, and infection with mixed pathogenic bacteria are the independent risk factors for the death of those patients.

Natural products are essential sources of antitumor drugs. One such molecule, β-elemene, is a potent antitumor compound extracted from Curcuma wenyujin. In the present investigation, a series of novel 13,14-disubstituted nitric oxide (NO)-donor β-elemene derivatives were designed, with β-elemene as the foundational compound, and subsequently synthesized to evaluate their therapeutic potential against leukemia. Notably, the derivative labeled as compound 13d demonstrated a potent anti-proliferative activity against the K562 cell line, with a high NO release. In vivo studies indicated that compound 13d could effectively inhibit tumor growth, exhibiting no discernible toxic manifestations. Specifically, a significant tumor growth inhibition rate of 62.9% was observed in the K562 xenograft tumor mouse model. The accumulated data propound the potential therapeutic application of compound 13d in the management of leukemia.
Humans ; Mice ; Animals ; Cell Line, Tumor ; Nitric Oxide Donors/pharmacology* ; Sesquiterpenes/pharmacology* ; Leukemia/drug therapy* ; Biological Assay ; Cell Proliferation

Objective: To analyze the spatio-temporal distribution characteristics of new HIV/AIDS cases at ages of 50 years and older in Wenzhou City from 2006 to 2020, so as to provide insights into precise control of AIDS. Methods : The data of new HIV/AIDS cases aged 50 years and older in Wenzhou City from 2006 to 2020 were collected from the China Information System for Disease Control and Prevention. The temporal and spatial distribution characteristics of new HIV/AIDS cases at ages of 50 years and older were identified using global and local spatial autocorrelation analyses and spatial-temporal scan analysis. Results: Totally 1 917 new HIV/AIDS cases aged 50 years and older were detected in Wenzhou City from 2006 to 2020, and there were 179 new HIV/AIDS cases in 58 townships ( streets ) from 2006 to 2010, 643 cases in 113 townships ( streets ) from 2011 to 2015 and 1 095 cases in 147 townships ( streets ) from 2016 to 2020, respectively. The distribution of new HIV/AIDS cases appeared positive spatial autocorrelations from 2006 to 2010 ( Moran's I value=0.05, Z=1.976, P=0.046 ), from 2011 to 2015 ( Moran's I value=0.08, Z=2.314, P=0.028) and from 2016 to 2020 (Moran's I value=0.18, Z=3.956, P=0.003 ). Spatial-temporal scan analysis identified two clusters. The primary cluster mainly covered 70 towns ( streets ) in Lucheng Distrct, Ouhai District, Longwan District, Economic and Technical Development Region, Rui' an City and Pingyang County of Wenzhou City from January 1, 2014 to December 31, 2020, with a cluster radius of 34.30 km [log likelihood ratio ( LLR )=192.84, RR=2.60, P<0.001], and the secondary cluster was located in Hongqiao Township of Yueqing City from January 1, 2009 to December 31, 2015, with a cluster radius of 0 ( LLR=90.60, RR=7.27, P<0.001 ). Conclusions The number of new HIV/AIDS cases aged 50 years and older appeared a tendency towards a rise in Wenzhou City from 2006 to 2020, with spatial clusters that were predominantly identified in urban areas, Rui' an City and Pingyang County of Wenzhou City.

Objective:To investigate the clinical effects of medical ozone autologous blood transfusion combined with Xingnaojing in the treatment of septic encephalopathy in burns.Methods:The retrospective cohort study was conducted. From August 2015 to May 2019, 90 patients with burn septic encephalopathy and conforming to the inclusion criteria were admitted to Zhengzhou First People's Hospital. Forty-six patients (25 males and 21 females, aged (35±4) years ) treated with Xingnaojing were included in Xingnaojing alone group, and forty-four patients (20 males and 24 females, aged (34±5) years) treated with medical ozone autologous blood transfusion combined with Xingnaojing were included in ozone autologous blood transfusion+Xingnaojing group. Heart rate, body temperature, mean arterial pressure, acute physiology and chronic health evaluation Ⅱ(APACHEⅡ) score and Glasgow coma score (GCS) of patients in 2 groups were recorded before treatment and on 7 d after treatment. The blood-brain barrier injury markers including occludin, nitric oxide synthase (NOS), neuron-specific enolase (NSE), central nervous system specific protein S100β, glial fibrillar acidic protein (GFAP), and excitatory amino acid (EAA) in serum of patients in 2 groups were detected before treatment and on 1, 3, and 7 d after treatment. Computer tomography perfusion imaging for brain was performed in patients of 2 groups to calculate the region of interest cerebral blood flow (rCBF), region of interest blood volume (rCBV), and region of interest mean transit time (rMTT) before treatment and on 1, 3, and 7 d after treatment. Data were statistically analyzed with chi-square test, analysis of variance for repeated measurement, independent sample t test, and Bonferroni correction. Results:On 7 d after treatment, heart rate, body temperature, and mean arterial pressure of patients in 2 groups were decreased compared with those before treatment, heart rate of patients in ozone autologous blood transfusion+Xingnaojing group was obviously higher than that in Xingnaojing alone group ( t=2.886, P<0.01), body temperature of patients in ozone autologous blood transfusion+Xingnaojing group was obviously lower than that in Xingnaojing alone group ( t=5.020, P<0.01), and mean arterial pressure of patients in 2 groups were close ( t=0.472, P>0.05). On 7 d after treatment, APACHEⅡ score of patients in ozone autologous blood transfusion+Xingnaojing group was obviously lower than that in Xingnaojing alone group ( t=3.797, P<0.01), and GCS of patients in ozone autologous blood transfusion+Xingnaojing group was obviously higher than that in Xingnaojing alone group ( t=4.934, P<0.01). On 3 and 7 d after treatment, the levels of occludin, NOS, NSE, S100β, GFAP, and EAA in serum of patients in ozone autologous blood transfusion+Xingnaojing group were significantly lower than those in Xingnaojing alone group ( t=2.100, 2.090, 2.691, 2.013, 2.474, 2.635, 2.225, 4.011, 3.150, 2.691, 3.145, 2.781, P<0.05 or P<0.01). On 1, 3, and 7 d after treatment, rCBF and rCBV of patients in ozone autologous blood transfusion+Xingnaojing group were significantly increased compared with those in Xingnaojing alone group ( t=3.127, 3.244, 3.883, 7.274, 3.661, 2.777, P<0.01). On 7 d after treatment, rMTT of patients in ozone autologous blood transfusion+Xingnaojing group was (3.02±0.57) s, which was significantly lower than (3.11±1.20) s in Xingnaojing alone group ( t=2.409, P<0.05). Conclusions:Transfusion of medical ozone autologous blood combined with Xingnaojing therapy can effectively relieve brain injury and improve cerebral blood perfusion in patients with burn septic encephalopathy, which is with safety and credibility.

Objective:To explore the value of renal injury marker protein in early diagnosis of acute kidney injury (AKI) in burn patients with delayed resuscitation.Methods:The retrospective case-control research was conducted. Forty-three burn patients with delayed resuscitation (27 males and 16 females, with age of 18-75 (35±3) years)who were admitted to Zhengzhou First People′s Hospital from May 2018 to May 2020 met the inclusion criteria. The patients were divided into AKI group with 23 patients and non-AKI group with 20 patients according to whether AKI occurred within 7 days after burns. The gender, age, deep partial-thickness burn area, full-thickness burn area, and acute physiology and chronic health evaluation Ⅱ of patients were compared between the two groups.The fluid supplement volume and serum creatinine at 12, 24, and 48 h after burn, serum albumin/fibrinogen ratio (AFR), urinary heat shock protein 70 (HSP70), tissue inhibitor of metalloproteinase-2 (TIMP-2)×insulin-like growth factor binding protein 7 (IGFBP-7), and neutrophil gelatinase associated lipocalin (NGAL)at 12, 24, 48, 72, 120, and 168 h after burn were detected.Data were statistically analyzed with Mann-Whitney U test, analysis of variance for repeated measurement, independent-samples t test, chi-square test and Bonferroni correction. The independent variable to predict the occurrence of AKI was screened by multi-factor logistic regression analysis. The receiver′s operating characteristic curve was drawn for predicting the occurrence of AKI in burn delayed resuscitation patients, and the area under the curve (AUC), the best threshold, and the sensitivity and specificity under the best threshold were calculated. Results:The gender, age, deep partial-thickness burn area, full-thickness burn area, acute physiology and chronic health evaluation Ⅱ of patients in two groups were similar ( χ2=1.98, t=1.98, 1.99, 1.99, 1.99, P>0.05). The fluid supplement volume of patients in AKI group at 24 and 48 h after burn was significantly less than that in non-AKI group ( t=15.37, 6.51, P<0.01). The serum creatinine of patients in AKI group at 12, 24, and 48 h after burn was significantly higher than that in non-AKI group ( Z=2.16, 5.62, 6.72, P<0.01). The serum AFR of patients in AKI group at 12, 24, 48, 72, 120, and 168 h after burn was significantly lower than that in non-AKI group ( t=16.14, 35.35, 19.60, 20.47, 30.20, 20.17, P<0.01). The levels of urinary HSP70 of patients in AKI group at 12, 24, 48, 72, 120, and 168 h after burn were (6.89±0.87), (6.42±0.73), (5.81±0.72), (5.17±0.56), (4.63±0.51), (3.89±0.51) μg/L, which were significantly higher than (3.89±0.75), (3.57±0.63), (2.66±0.41), (1.83±0.35), (1.48±0.19), (1.28±0.19) μg/L in non-AKI group ( t=12.00, 13.61, 17.39, 22.98, 26.34, 21.59, P<0.01). Urinary TIMP-2×IGFBP-7 and NGAL of patients in AKI group at 12, 24, 48, 72, 120, 168 h after burn were significantly higher than those in non-AKI group ( t=26.94, 101.11, 35.50, 66.89, 17.34, 14.30, 14.00, 13.78, 12.32, 14.80, 21.36, 22.62, P<0.01). Urinary HSP70 and serum AFR at 12 h after burn, urinary TIMP-2×IGFBP-7 and NGAL at 24 h after burn were included into multi-factor logistic regression analysis (odds ratio=2.42, 3.47, 7.52, 5.61, 95% confidence interval=1.99-2.95, 1.86-3.92, 2.87-9.68, 2.14-14.69, P<0.01). For 43 patients with burn delayed resuscitation, the AUC of receiver′s operating characteristic curve of serum AFR at 12 h after burn for predicting AKI was 0.739 (95% confidence interval=0.576-0.903), the optimal threshold was 9.90, the sensitivity was 82%, and the specificity was 90%. The AUC of urinary HSP70 at 12 h after burn was 0.990 (95% confidence interval=0.920-1.000), the optimal threshold was 1.40 μg/L, the sensitivity was 98%, and the specificity was 96%. The AUC of urinary TIMP-2×IGFBP-7 at 24 h after burn was 0.715 (95% confidence interval=0.512-0.890), the optimal threshold was 114.20 μg 2/L 2, the sensitivity was 91%, and the specificity was 95%. The AUC of urinary NGAL at 24 h after burn was 0.972 (95% confidence interval=0.860-1.000), the optimal threshold was 78 μg/L, the sensitivity was 95%, and the specificity was 96%. Conclusions:Urinary HSP70 and NGAL have higher value in early diagnosis of AKI in burn patients with delayed resuscitation.

【Objective】 To investigate the role of thromboelastography (TEG) in the diagnosis and treatment of PICC related venous thrombosis in tumor patients, and provide basis for predicting PIC related venous thrombosis. 【Methods】 148 tumor patients who underwent PICC catheterization in our hospital from January to July 2019 were enrolled. The patients were subjected to TEG examination and ultrasound examination of limb blood vessels on catheterization side regularly one day before catheterization and 4 successive weeks after catheterization(once a week), respectively. The patients with venous thrombosis were subjected to TEG examination and vascular ultrasound regularly for 3 successive weeks(once a week) after anticoagulant therapy. The relationship between the occurrence and time of venous thrombosis and the changes of TEG parameters was analyzed. 【Results】 The pre-/post-catheterization TEG parameter of 81 patients without venous thrombosis indicated that coagulation state was normal (R value F=0.198, K value F=0.047, α value F=0.442, MAvalue F=0.079, CIvalue F=0.026, P>0.05). The TEG parameter of 67 patients, who developed asymptomatic venous thrombosis 1 to 3 weeks after catheterization(38 cases in 1 week, 16 in 2 weeks and 13 in 3 weeks), indicated the blood was hypercoagulable and the TEG parameter was statistically different from the pre-catheterization value(P<0.01). But after anticoagulant treatment, the coagulation state gradually returned to normal as the TEG parameter reached pre-catheterization value for 3 successive weeks (P>0.05). 【Conclusion】 TEG can reflect the status of PICC related venous thrombosis in tumor patients.Strengthening TEG monitor in tumor patients 1 to 3 weeks after PICC catheterization is conducive to early detection, diagnosis and treatment for PICCrelated thrombosis, thus reducing the harm of venous thrombosis to patients.