The precise and rapid monitoring of multiple organ dysfunction is crucial in drug discovery. Traditional methods, such as pathological analysis, are often time-consuming and inefficient. Here, we developed a multiplexed near-infrared window two (NIR-II) fluorescent bioimaging method that allows for real-time, rapid, and quantitative assessment of multiple organ dysfunctions. Given that existing probes did not fully meet requirements, we synthesized a range of NIR-II hemicyanine dyes (HDs) with varying absorption and emission wavelengths. By modifying these dyes, we achieved high spatial and temporal resolution imaging of the liver, kidneys, stomach, and intestines. This method was further applied to investigate disorders induced by cisplatin, a drug known to cause gastric emptying issues along with liver and kidney injuries. By monitoring the metabolic rate of the dyes in these organs, we accurately quantified multi-organ dysfunction, which was also confirmed by gold-standard pathological analysis. Additionally, we evaluated the effects of five aristolochic acids (AAs) on multiple organ dysfunction. For the first time, we identified that AA-I and AA-II could cause gastric emptying disorders, which was further validated through transcriptomics analysis. Our study introduces a novel approach for the simultaneous monitoring of multi-organ dysfunction, which may significantly enhance the evaluation of drug side effects.

[摘 要] 目的：探究包被蛋白复合体β1亚基（COPB1）在食管鳞状细胞癌（ESCC）中的表达，及其对ESCC细胞恶性生物学行为的影响、作用机制及临床意义。方法：采用2014～2018年间在河北医科大学第四医院生物样本库中82例ESCC组织及癌旁组织，常规培养正常食管鳞状上皮细胞HEEC和食管癌细胞KYSE-150、KYSE-170、Eca109、TE1、KYSE-30、KYSE-450，用转染试剂将pcDNA3.1-vector（空载体）、pcDNA3.1-COPB1载体，si-NC和si-COPB1转染至KYSE-150、TE1细胞中，记为NC、COPB1-OE、si-NC和si-COPB1组。用数据库数据分析COPB1 mRNA在泛癌组织中的表达及其表达与免疫细胞浸润的关系，qPCR法检测ESCC组织和细胞中COPB1、PIK3CB、CD68、CD163、CD206、ARG1、IL-10 mRNA水平表达情况，WB法检测ESCC组织和各组细胞中的COPB1、PI3K、CD68、CD163、CD206、p-AKT蛋白表达，克隆形成实验和MTS实验检测各组细胞的增殖能力，划痕愈合实验和Transwell实验检测各组细胞的迁移和侵袭能力，免疫组织化学染色（IHC）法检测ESCC组织中COPB1和CD206蛋白表达。以人单核细胞白血病细胞（THP-1）构建巨噬细胞模型，用佛波酯（PMA）和IL-3和IL-4和ESCC细胞上清液诱导巨噬细胞转型，用qPCR和WB法检测CD68和CD206m RNA和蛋白的表达。结果：COPB1在泛癌组织和ESCC组织中均呈高表达且与淋巴结转移和TNM分期有关联（均P < 0.01），COPB1高表达的ESCC患者总生存期短（P < 0.05），COPB1是潜在的ESCC的诊断标志物。COPB1在KYSE-150和TE1细胞中也呈高表达（均P < 0.05），过表达或敲减COPB1可明显抑制或促进KYSE-150和TE1细胞的增殖能力、迁移和侵袭能力（均P < 0.05）。COPB1表达变化诱导的差异表达基因主要富集于PI3K/AKT通路（均P < 0.001）, COPB1可促进PI3K/AKT通路的活化（P < 0.05），COPB1高表达可导致M2型巨噬细胞浸润增加（P < 0.05），COPB1高表达促进TAM/M2极化（P < 0.05）。结论：COPB1在ESCC组织中呈高表达，其可激活PI3K/AKT通路及调控肿瘤免疫微环境促进 ESCC发生发展，COPB1有望成为ESCC诊断和预后的生物标志物及治疗靶点。

Objective To observe the effect of Magu Xujin capsule on clinical symptoms and bone metabolism after intramedullary nail fixation of proximal humerus fracture.Methods Eighty-two patients with proximal humeral fractures treated with intramedullary nailing were randomly divided into two groups,with 41 cases in each group.The conventional group was given routine anti-swelling and pain-relieving symptomatic treatment after surgery,while the experimental group was given Magu Xujin capsules(2 capsules each time,3 times a day,for 8 consecutive weeks)on the basis of the conventional group.Changes in shoulder joint circumference difference,shoulder joint pain score,Neer shoulder joint function score and callus growth score were compared between the two groups.The serum levels of osteocalcin(BGP),N-terminal osteocalcin(N-MID),bone morphogenetic protein 2(BMP-2)and blood calcium were detected by enzyme-linked immunosorbent assay.The occurrence of complications and adverse reactions was analyzed in the two groups.Results Changes of shoulder joint circumference difference at 3,5,7 and 14 days after surgery were lower than those at 1 day after surgery in both groups,and changes of the shoulder joint circumference difference were smaller in the experimental group at 3,5,7 and 14 days after surgery than those in the conventional group(P＜0.01).The shoulder joint pain scores in both groups at 3,5,7 and 14 days after surgery and at 4 and 8 weeks were lower than those at 1 day after surgery,and the score was lower in the experimental group than that in the conventional group(P＜0.01).The serum levels of BGP,N-MID,BMP-2 and blood calcium in both groups at 4 and 8 weeks after surgery were higher than those before surgery(P＜0.05),and the levels in the experimental group were higher than those in the conventional group(P＜0.05).The Neer scores in both groups at 4 and 8 weeks after surgery were higher than those before surgery(P＜0.05).The Neer score and callus growth score at 4 and 8 weeks after surgery were higher in the experimental group than those in the conventional group(P＜0.05).In the conventional group,there were two cases of delayed fracture healing and one case of soft tissue infection after surgery.No adverse reactions occurred in either group.Conclusion Magu Xujin capsules can promote the reduction of swelling after intramedullary nail fixation surgery for proximal humeral fractures,alleviate shoulder joint pain,improve bone metabolism and promote the recovery of shoulder joint function.

Objective:To investigate the clinical characteristics of children with cervicothoracic hemivertebra at different ages and evaluate the surgical outcomes of hemivertebra resection.Methods:This retrospective cohort study analyzed clinical and radiographic data of 35 children (under 18 years old) with cervicothoracic hemivertebra who underwent one-stage posterior hemivertebra resection at the Department of Spine Surgery, Second Xiangya Hospital of Central South University, from June 2005 to June 2022. The cohort included 19 males and 16 females, with a surgical age of (9.7±4.1) years (range: 3 to <18 years). Patients were divided into three groups based on initial surgical age: preschool group (≤5 years, n=10), school-age group (6 to 10 years, n=10), and adolescent group (11 to <18 years, n=15). The intraoperative blood loss, operative time, number of fixed vertebrae, and perioperative and postoperative complications were recorded. Radiographic measurements were taken preoperatively, postoperatively, and at final follow-up, including the Cobb angle of the primary curve, curve length, distal curve Cobb angle, neck tilt, shoulder balance, coronal balance, trunk tilt, clavicle angle, head deviation, and local kyphosis. Statistical analyses included one-way ANOVA, Kruskal-Wallis H test, chi-square test, and Fisher′s exact test. Results:The operative time was (333±74) minutes (range:200 to 450 minutes), the intraoperative blood loss was (419±132) ml (range:200 to 650 ml), and the number of fixed vertebrae was (6.0±2.7) segments (range:2 to 12 segments). Preoperatively, the preschool group had a smaller primary curve Cobb angle compared to the adolescent group (33.6°±8.4° vs. 43.0°±9.4°, F=3.394, P=0.046) and distal curve Cobb angle (6.4°±2.4° vs.11.9°±4.5°, F=6.550, P=0.038). The preschool group had better coronal balance ((8.8±4.3) mm vs. (20.2±11.7)mm, F=9.448, P=0.009) and trunk tilt (4.0°±2.0° vs.7.0°±3.0°, F=4.343, P=0.029) than the school-age group. The preschool group had fewer fused vertebrae than the school-age and adolescent groups (3.8±1.6 vs. 7.0±2.6 vs. 6.8±2.6, F=10.480, P=0.005). The preschool group also had less intraoperative blood loss than the adolescent groups ((320±125) ml vs. (480±113) ml, F=8.666, P=0.013). However, no significant differences were found in postoperative and final follow-up measurements of primary and distal curve Cobb angles, neck tilt, shoulder balance, coronal balance, trunk tilt, clavicle angle, head deviation, local kyphosis, or complication rates (all P>0.05). Conclusions:Children with cervicothoracic hemivertebra across different age groups exhibit similar surgical outcomes and complication rates. But the preschool group had fewer fixed segments and less intraoperative blood loss, suggesting that this age group is an ideal time for surgery.

Objective To observe the effect of Magu Xujin capsule on clinical symptoms and bone metabolism after intramedullary nail fixation of proximal humerus fracture.Methods Eighty-two patients with proximal humeral fractures treated with intramedullary nailing were randomly divided into two groups,with 41 cases in each group.The conventional group was given routine anti-swelling and pain-relieving symptomatic treatment after surgery,while the experimental group was given Magu Xujin capsules(2 capsules each time,3 times a day,for 8 consecutive weeks)on the basis of the conventional group.Changes in shoulder joint circumference difference,shoulder joint pain score,Neer shoulder joint function score and callus growth score were compared between the two groups.The serum levels of osteocalcin(BGP),N-terminal osteocalcin(N-MID),bone morphogenetic protein 2(BMP-2)and blood calcium were detected by enzyme-linked immunosorbent assay.The occurrence of complications and adverse reactions was analyzed in the two groups.Results Changes of shoulder joint circumference difference at 3,5,7 and 14 days after surgery were lower than those at 1 day after surgery in both groups,and changes of the shoulder joint circumference difference were smaller in the experimental group at 3,5,7 and 14 days after surgery than those in the conventional group(P＜0.01).The shoulder joint pain scores in both groups at 3,5,7 and 14 days after surgery and at 4 and 8 weeks were lower than those at 1 day after surgery,and the score was lower in the experimental group than that in the conventional group(P＜0.01).The serum levels of BGP,N-MID,BMP-2 and blood calcium in both groups at 4 and 8 weeks after surgery were higher than those before surgery(P＜0.05),and the levels in the experimental group were higher than those in the conventional group(P＜0.05).The Neer scores in both groups at 4 and 8 weeks after surgery were higher than those before surgery(P＜0.05).The Neer score and callus growth score at 4 and 8 weeks after surgery were higher in the experimental group than those in the conventional group(P＜0.05).In the conventional group,there were two cases of delayed fracture healing and one case of soft tissue infection after surgery.No adverse reactions occurred in either group.Conclusion Magu Xujin capsules can promote the reduction of swelling after intramedullary nail fixation surgery for proximal humeral fractures,alleviate shoulder joint pain,improve bone metabolism and promote the recovery of shoulder joint function.

Objective:To investigate the level of rehabilitation exercise adherence in patients undergoing anterior cruciate ligament (ACL) reconstruction within 6 months post-surgery, analyze its trajectory, and provide a reference for clinical nursing interventions.Methods:Using a convenience sampling method, 150 patients who underwent arthroscopic ACL reconstruction at the First Affiliated Hospital of Zhengzhou University from June 2022 to August 2023 were selected. Rehabilitation exercise adherence was assessed monthly from postoperative 1 month (M 1) to 6 months (M 6) using the Orthopedic Functional Exercise Adherence Scale. A latent class growth model was employed to analyze adherence trajectory categories, and Logistic regression was used to identify influencing factors for different adherence trajectories. Results:A total of 144 patients completed follow-up (follow-up rate was 96.00%). Exercise adherence scores gradually declined over the 6 months post-surgery, with scores of (50.30±5.39), (45.92±3.85), (39.48±5.27), (35.83±6.19), (31.85±7.59), and (29.88±7.88) from M 1 to M 6, respectively. The difference in scores across time points was statistically significant ( F=85.467, P<0.01). Three potential categories were identified through the latent class growth model: the moderate-high level rapid decline group ( n=65, 45.14%), the moderate-low level stable group ( n=32, 22.22%), and the moderate-low level slow decline group ( n=47, 32.64%). Logistic regression analysis revealed that gender and age were significant factors influencing adherence trajectory categories ( P<0.05) . Conclusions:Dynamic declines in rehabilitation exercise adherence are common among ACL reconstruction patients, with varying degrees of decline. Gender and age may influence adherence trajectories, suggesting that targeted management strategies could be implemented in clinical practice.

The orthobunyavirus is a major group of mosquito-borne viruses，mainly prevalent in the Americas，Europe，and Africa. It can cause severe human diseases（e.g.，encephalitis，hemorrhagic fever）and livestock abortions. Reverse genetics，as a powerful tool for viral genome research，has been widely applied to study viral gene functions，develop vaccines，and screen antiviral drugs. This review systematically presents the evolutionary history and applications of the reverse genetics system for orthobunyaviruses，providing critical insights into studies on the infection and transmission mechanisms of these viruses，as well as the development of novel vaccines and therapeutic agents.

The orthobunyavirus is a major group of mosquito-borne viruses，mainly prevalent in the Americas，Europe，and Africa. It can cause severe human diseases（e.g.，encephalitis，hemorrhagic fever）and livestock abortions. Reverse genetics，as a powerful tool for viral genome research，has been widely applied to study viral gene functions，develop vaccines，and screen antiviral drugs. This review systematically presents the evolutionary history and applications of the reverse genetics system for orthobunyaviruses，providing critical insights into studies on the infection and transmission mechanisms of these viruses，as well as the development of novel vaccines and therapeutic agents.

Objective:To investigate the clinical characteristics of children with cervicothoracic hemivertebra at different ages and evaluate the surgical outcomes of hemivertebra resection.Methods:This retrospective cohort study analyzed clinical and radiographic data of 35 children (under 18 years old) with cervicothoracic hemivertebra who underwent one-stage posterior hemivertebra resection at the Department of Spine Surgery, Second Xiangya Hospital of Central South University, from June 2005 to June 2022. The cohort included 19 males and 16 females, with a surgical age of (9.7±4.1) years (range: 3 to <18 years). Patients were divided into three groups based on initial surgical age: preschool group (≤5 years, n=10), school-age group (6 to 10 years, n=10), and adolescent group (11 to <18 years, n=15). The intraoperative blood loss, operative time, number of fixed vertebrae, and perioperative and postoperative complications were recorded. Radiographic measurements were taken preoperatively, postoperatively, and at final follow-up, including the Cobb angle of the primary curve, curve length, distal curve Cobb angle, neck tilt, shoulder balance, coronal balance, trunk tilt, clavicle angle, head deviation, and local kyphosis. Statistical analyses included one-way ANOVA, Kruskal-Wallis H test, chi-square test, and Fisher′s exact test. Results:The operative time was (333±74) minutes (range:200 to 450 minutes), the intraoperative blood loss was (419±132) ml (range:200 to 650 ml), and the number of fixed vertebrae was (6.0±2.7) segments (range:2 to 12 segments). Preoperatively, the preschool group had a smaller primary curve Cobb angle compared to the adolescent group (33.6°±8.4° vs. 43.0°±9.4°, F=3.394, P=0.046) and distal curve Cobb angle (6.4°±2.4° vs.11.9°±4.5°, F=6.550, P=0.038). The preschool group had better coronal balance ((8.8±4.3) mm vs. (20.2±11.7)mm, F=9.448, P=0.009) and trunk tilt (4.0°±2.0° vs.7.0°±3.0°, F=4.343, P=0.029) than the school-age group. The preschool group had fewer fused vertebrae than the school-age and adolescent groups (3.8±1.6 vs. 7.0±2.6 vs. 6.8±2.6, F=10.480, P=0.005). The preschool group also had less intraoperative blood loss than the adolescent groups ((320±125) ml vs. (480±113) ml, F=8.666, P=0.013). However, no significant differences were found in postoperative and final follow-up measurements of primary and distal curve Cobb angles, neck tilt, shoulder balance, coronal balance, trunk tilt, clavicle angle, head deviation, local kyphosis, or complication rates (all P>0.05). Conclusions:Children with cervicothoracic hemivertebra across different age groups exhibit similar surgical outcomes and complication rates. But the preschool group had fewer fixed segments and less intraoperative blood loss, suggesting that this age group is an ideal time for surgery.