1.Ferroptosis and osteoporosis
Cheng YANG ; Weimin LI ; Dongcheng RAN ; Jiamu XU ; Wangxiang WU ; Jiafu XU ; Jingjing CHEN ; Guangfu JIANG ; Chunqing WANG
Chinese Journal of Tissue Engineering Research 2025;29(3):554-562
BACKGROUND:It has also been confirmed that ferroptosis is closely related to a variety of musculoskeletal diseases,such as rheumatoid arthritis,osteosarcoma,and osteoporosis.The pathophysiological mechanisms of ferroptosis and osteoporosis need to be further studied and elucidated to broaden our understanding of iron metabolism and osteoporosis.It will provide research ideas for the future elucidation of new mechanisms of osteoporosis and the development of new technologies and drugs for the treatment of osteoporosis. OBJECTIVE:To provide an overview of the current status of research on ferroptosis in osteoporosis,to provide a new direction for future research on the specific molecular mechanisms of osteoporosis,and to provide more effective and better options for osteoporosis treatment strategies. METHODS:The first author used the computer to search the literature published from 2000 to 2024 in CNKI,WanFang,VIP,and PubMed databases with search terms"ferroptosis,iron metabolism,osteoporosis,osteoblast,osteoclast,bone metabolism,signal pathway,musculoskeletal,review"in Chinese and English.A total of 68 articles were finally included according to the selection criteria. RESULTS AND CONCLUSION:(1)Ferroptosis is a new type of cell death discovered in recent years,which is usually accompanied by a large amount of iron accumulation and lipid peroxidation during cell death,and its occurrence is iron-dependent.This is distinctly different from several types of cell death that are currently being hotly studied(e.g.,cellular pyroptosis,necrotic apoptosis,cuproptosis,and autophagy).(2)Intracellular iron homeostasis is manifested as a balance between iron uptake,export,utilization,and storage.The body's iron regulatory system includes systemic and intracellular regulation.The main factor of systemic regulation is hepcidin produced by hepatic secretion,and cellular regulation depends on the iron regulatory protein/iron response element system.Of course,intracellular iron homeostasis can be controlled by other factors,such as hypoxia,cytokines,and hormones.(3)Lipid peroxidation causes oxidative damage to biological membranes(plasma membrane and internal organelle membranes),lipoproteins,and other lipid-containing molecules.Polyunsaturated fatty acid-containing phospholipids are important targets of lipid peroxidation.Free polyunsaturated fatty acid is an important substrate for lipid oxidation and can bind to the phospholipid bilayer,leading to over-oxidation and thus triggering lipid apoptosis.(4)Several studies have shown that osteoblasts are overloaded with iron in different ways,resulting in the accumulation of unstable ferrous iron and the generation of reactive oxygen species and lipid peroxides,causing ferroptosis of osteoblasts and ultimately a decrease in bone formation,affecting bone homeostasis and the development of osteoporosis.(5)Osteoclasts are large multinucleated cells formed by the fusion of mononuclear macrophage cell lines or bone marrow mesenchymal stem cells induced by nuclear factor-κB ligand receptor activator,and they have the function of bone resorption.Iron ions can promote osteoclast differentiation and bone resorption through the production of intracellular lipid reactive oxygen species,while iron chelators can inhibit osteoclast formation in vitro and thus affect the occurrence and development of osteoporosis.
2.Endoscopic assisted surgery combined with sclerotherapy injection and negative pressure drainage for the treatment of children with microcystic lymphatic malformation
Weidong WANG ; Tao HAN ; Haini CHEN ; Jie CUI ; Weimin SHEN
Chinese Journal of Plastic Surgery 2025;41(11):1130-1135
Objective:To investigate the feasibility and effect of endoscopic assisted surgery combined with sclerosing agent injection and negative pressure drainage for the treatment of microcystic lymphatic malformation in children.Methods:A retrospective analysis was conducted on clinical data of pediatric patients with microcystic lymphatic malformations between December 2021 and December 2023 in the Department of Burns and Plastic Surgery at Children’s Hospital of Nanjing Medical University. The treatment protocol consisted of endoscope-assisted surgery combined with sclerotherapy and negative pressure drainage. Preoperatively, two-dimensional ultrasound was utilized to demarcate the surface extent of the malformation. Intraoperatively, subcutaneous lymphatic malformation tissues were resected as thoroughly as possible under endoscopic guidance, and cystic cavities were interconnected. Postoperatively, a drainage tube was placed and connected to a negative pressure system. Starting on the third postoperative day, the cystic cavity was irrigated with absolute ethanol every other day. Irrigation was continued until the drainage fluid became light yellow and clear, and the daily drainage volume fell below 5 ml, at which point the drainage tube was removed. Complications were monitored, and treatment efficacy was assessed at the last follow-up using a four-tiered outcome scale: cured, markedly effective, effective, and ineffective. The overall effectiveness rate was calculated as (cured + markedly effective + effective) cases/total number of cases × 100%. Data analysis was performed using descriptive statistics.Results:A total of 20 pediatric patients were enrolled, including 8 males and 12 females. The age range was from 1 month to 13 years, with a mean age of 7 years and 7 months. All lesions were located superficially, distributed as follows: head, face, and neck (8 cases), chest (2 cases), abdomen (3 cases), back (2 cases), and limbs (5 cases). The lesion volumes ranged from 5.8 cm × 4.2 cm × 3.8 cm to 14.5 cm × 10.4 cm × 8.4 cm. No complications such as absolute ethanol intoxication, severe allergic reactions, surgical site infection, neurovascular injury, thrombosis, or pulmonary embolism occurred during the treatment period. All patients had their negative pressure drainage tubes removed on postoperative day 10. After tube removal, one case developed serous drainage from the incision, which resolved after 4 days of wound care and compressive dressing. The remaining 19 cases demonstrated satisfactory incision healing. During a follow-up period of 6 to 12 months, no significant postoperative scarring and recurrence were observed. Treatment outcomes were as follows: 4 cases of cured, 10 cases of markedly effective, 5 cases of effective, and 1 case of ineffective. The overall effective rate was 95%(19/20).Conclusion:The integrated approach of endoscope-assisted surgery combined with sclerotherapy and negative pressure drainage for the treatment of microcystic lymphatic malformations in children yields definite and favorable outcomes. This comprehensive technique is characterized by its minimal invasiveness, stable long-term result as confirmed by follow-up, absence of severe complications, and a low recurrence rate.
3.Improvement effect of ginseng alcohol extract on sleep of aged drosophila and its mechanism
Jian LIU ; Lu XING ; Tianye LAN ; Fan YAO ; Wen WANG ; Yufu DONG ; Jinpu WU ; Ran BI ; Liwei SUN ; Xuenan CHEN ; Weimin ZHAO
Journal of Jilin University(Medicine Edition) 2025;51(4):896-903
Objective:To investigate the impact of ginseng alcohol extract(GEE)on improving sleep quality in the aged Drosophila model by regulating the redox balance,and to elucidate its associated mechanism.Methods:Thirty-two male drosophila melanogaster(7-days-old)were randomly selected as young group,while 64 male Drosophila melanogaster flies(35-days-old)were randomly assigned to aged model group(n=32)and GEE group(n=32).The sleep parameters,including total sleep duration,daytime sleep duration,night sleep duration,0-4 h of sleep duration after lights off(ZT0-4 sleep duration),deep sleep duration,sleep episodetimes,sleep fragmentation,and the activity parameters such as the total number of locomotor activity daytime locomotor activity amount and nighttime locomotor activity amount were analyzed using the DAM2 Drosophila behavioral analysis system 7 d after administration.The grouping of the drosophila was as above,and there were 100 drosophila ineach group.The differentially expressed proteins in drosophila brain tissue were screened,identified,and functionally analyzed using two-dimensional fluorescence difference gel electrophoresis(2D-DIGE)and matrix-assisted laser desorption/ionization time of flight mass spectrometry(MALDI-TOF/TOF-MS)proteomic methods.The grouping of the drosophila was as above,and there were 100 drosophila in each group.The activities of superoxide dismutase(SOD),catalase(CAT),and glutathione peroxidase(GSH-Px)and the levels of lipid peroxidation product(MDA)in brain tissue of the drosophila were determined using assay kits.Results:Compared with young group,the total sleep duration daytime sleep duration and night sleep cluration of the drosophila in agaed group were decreased(P<0.05 or P<0.01);and the sleep rhythm amplitude was shortened.Compared with aged group,the total sleep duration and daytime and nighttime sleep durations of the drosphila in GEE group were lengthened(P<0.01).Compared with young group,the ZT0-4 sleep duration deep sleep duration and sleep fragment of the drosophila in aged group were decreased(P<0.05 or P<0.01),and the sleep rhythm amplitude was shortened.Compared with young group,the ZT0-4 sleep duration,deep sleep duration,and single sleep fragment of the drosphila in GEE group were significantly prolonged(P<0.01),and the sleep amplitude was increased.Compared with young group,there was no significant difference in diurnal spontaneous activity or total spontaneous activity of the drosophila in aged group(P>0.05),while the nocturnal spontaneous activity was significantly increased(P<0.05).Compared with aged group,the diurnal spontaneous activity,nocturnal spontaneous activity,and total spontaneous activity of the drosophila in GEE group were significantly decreased(P<0.05 or P<0.01).A total of 47 differentially expressed proteins were selected in the 2D-DIGE electrophoretic mapping.Compared with young group,the expressions of 47 differentially expressed protein sites in aged group were down-regulated mainly including glutathione S-transferase,peroxiredoxin 1 and dihydrolipoic dehydrogenase,which were related to redox balance.Compared with young group,the activities of SOD,CAT and GSH-Px in brain tissue of the drosophila in aged group were decreased(P<0.05 or P<0.01),and the level of MDA was increased(P<0.01);compared with aged group,the activities of SOD,CAT and GSH-Px in brain tissue of the drosphila in GEE group were increased(P<0.05 or P<0.01),and the MDA level was decreased(P<0.05).Conclusion:GEE has improvement effect on the sleep quality of aged drosophila,and its possible mechanism may be related to upregulating the activities of antioxidant enzymes,inhibiting the accumulation of lipid peroxidation products,and maintaining redox balance.
4.Evidence-based guidelines for rehabilitation treatment after internal fixation of thoracolumbar spine fracture in adults (version 2025)
Zhengwei XU ; Liming CHENG ; Qixin CHEN ; Jian DONG ; Shunwu FAN ; Zhong FANG ; Shiqing FENG ; Haoyu FENG ; Haishan GUAN ; Weimin JIANG ; Dianming JIANG ; Yong HAI ; Lijun HE ; Yuan HE ; Bo LI ; Jianjun LI ; Feng LI ; Li LI ; Weishi LI ; Chunde LI ; Qi LIAO ; Baoge LIU ; Xiaoguang LIU ; Yong LIU ; Xuhua LU ; Shibao LU ; Bin LIN ; Wei MEI ; Chao MA ; Renfu QUAN ; Limin RONG ; Jiacan SU ; Honghui SUN ; Yuemin SONG ; Hongxun SANG ; Jun SHU ; Tiansheng SUN ; Jiwei TIAN ; Qiang WANG ; Xinwei WANG ; Zhe WANG ; Zheng WANG ; Liang YAN ; Guoyong YIN ; Jie ZHAO ; Yue ZHU ; Xiaobo ZHANG ; Xuesong ZHANG ; Zhongmin ZHANG ; Rongqiang ZHANG ; Dingjun HAO ; Yanzheng GAO ; Baorong HE
Chinese Journal of Trauma 2025;41(1):19-32
Thoracolumbar spine fracture often leads to severe pain, functional impairments, and neurological deficits, for which open reduction and internal fixation can effectively restore the spinal structural stability. Open decompression and reduction with internal fixation can help relieve spinal cord compression and improve spinal function in cases of concomitant cord injury. Although spinal stability can be restored through surgery, patients often face chronic pain and functional impairments postoperatively. A postoperative rehabilitation program is critical in optimizing therapeutic outcomes, reducing complications, and minimizing the risk of secondary injuries. However, current rehabilitation methods, such as physical therapy, functional training, and pain management, are confronted with problems in clinical practice, including significant variation in efficacy, poor patient adherence, and prolonged rehabilitation period. There is an urgent need for a unified rehabilitation strategy to address these problems. To this end, the Spinal Trauma Group of the Orthopedic Physicians Branch of the Chinese Medical Association and the Spine Health Professional Committee of the Chinese Human Health Technology Promotion Association organized experts from relevant fields to formulate Evidence-based guidelines for rehabilitation treatment after internal fixation of thoracolumbar spine fracture in adults ( version 2025) by integrating evidences from clinical researches and advanced rehabilitation concepts at home and abroad. A total number of 14 recommendations concerning the rehabilitation treatment with multimodal analgesia, psychological intervention, deep vein thrombosis prevention, core muscle and extremity exercise, appropriate use of braces, early weight-bearing, device-aided rehabilitation exercise, neuroregulatory therapy, rehabilitation team were put forward, aiming to standardize the post-operative rehabilitation process following internal fixation, promote the functional recovery, and enhance patients′ quality of life.
5.Clinical guideline for vertebral augmentation of acute symptomatic osteoporotic thoracolumbar compression fractures (version 2025)
Bolong ZHENG ; Wei MEI ; Yanzheng GAO ; Liming CHENG ; Jian CHEN ; Qixin CHEN ; Liang CHEN ; Xigao CHENG ; Jian DONG ; Jin FAN ; Shunwu FAN ; Xiangqian FANG ; Zhong FANG ; Shiqing FENG ; Haoyu FENG ; Haishan GUAN ; Yong HAI ; Baorong HE ; Lijun HE ; Yuan HE ; Hua HUI ; Weimin JIANG ; Junjie JIANG ; Dianming JIANG ; Xuewen KANG ; Hua GUO ; Jianjun LI ; Feng LI ; Li LI ; Weishi LI ; Chunde LI ; Qi LIAO ; Baoge LIU ; Xiaoguang LIU ; Xuhua LU ; Shibao LU ; Bin LIN ; Chao MA ; Xuexiao MA ; Renfu QUAN ; Limin RONG ; Honghui SUN ; Tiansheng SUN ; Yueming SONG ; Hongxun SANG ; Jun SHU ; Jiacan SU ; Jiwei TIAN ; Xinwei WANG ; Zhe WANG ; Zheng WANG ; Zhengwei XU ; Huilin YANG ; Jiancheng YANG ; Liang YAN ; Feng YAN ; Guoyong YIN ; Xuesong ZHANG ; Zhongmin ZHANG ; Jie ZHAO ; Yuhong ZENG ; Yue ZHU ; Rongqiang ZHANG
Chinese Journal of Trauma 2025;41(9):805-818
Acute symptomatic osteoporotic thoracolumbar compression fracture (ASOTLF) can lead to chronic low back pain, kyphosis deformity, pulmonary dysfunction, loss of mobility, and even life-threatening complications. Vertebral augmentation is currently the mainstream treatment method for this condition. In 2019, the Editorial Board of Chinese Journal of Trauma and the Spinal Trauma Group of Orthopedic Surgeons Branch of Chinese Medical Doctor Association collaboratively led the development of Clinical guideline for vertebral augmentation for acute symptomatic osteoporotic thoracolumbar compression fractures. Six years later, with advances in clinical diagnosis and treatment techniques as well as accumulating evidence in related fields, the 2019 guideline requires updating. To this end, the Spinal Trauma Group of Orthopedic Surgeons Branch of Chinese Medical Doctor Association, the Spinal Health Professional Committee of China Human Health Science and Technology Promotion Association, and the Minimally Invasive Orthopedics Professional Committee of Shaanxi Medical Doctor Association have organized experts in the field to develop the Clinical guideline for vertebral augmentation of acute symptomatic osteoporotic thoracolumbar compression fractures ( version 2025) , based on the latest evidence-based medical researches. This guideline incorporates 3 recommendations retained from the 2019 version with updated strength of evidence, along with 12 new recommendations. It provides recommendations from six aspects of diagnosis, pain management, treatment option selection, prevention of postoperative complications, anti-osteoporosis therapy, and postoperative rehabilitation, aiming to provide a reference for standard treatment of vertebral augmentation for ASOTLF in hospitals at all levels.
6.Analysis of the efficacy of total knee arthroplasty with partial varus retention in the treatment of moderate knee varus
Xing'an BAO ; Youquan CHEN ; Hao ZHOU ; Hui YANG ; Yi HUANG ; Weimin FAN ; Feng LIU
Chinese Journal of Orthopaedics 2025;45(6):327-334
Objective:To analyze the efficacy of total knee arthroplasty (TKA) with partial varus retention in the treatment of moderate knee varus.Methods:A retrospective analysis was conducted on the data of 613 osteoarthritis patients with moderate knee varus who underwent TKA at the First Affiliated Hospital of Nanjing Medical University from January 2010 to October 2019. According to whether a 2°-3° of knee varus was retained, the patients were divided into the retained varus group and the mechanical alignment group. The retained varus group included 318 cases, with 63 males and 255 females, aged 68.51±6.95 years (range, 46-86 years), and BMI of 26.99±3.66 kg/m 2 (range, 17.40-39.01 kg/m 2). Preoperative Kellgren-Lawrence (K-L) classification of knee osteoarthritis was grade III in 113 cases and grade IV in 205 cases. The mechanical alignment group included 295 cases, with 75 males and 220 females, aged 69.60±7.12 years (range, 52-87 years), and BMI of 26.95±3.94 kg/m 2 (range, 16.60-41.90 kg/m 2). Preoperative K-L classification was grade III in 102 cases and grade IV in 193 cases. Surgical duration, total blood loss, preoperative and postoperative varus angle, lower limb swelling on the fifth postoperative day, and postoperative complications were recorded. Follow-up were arranged at 3 months, 6 months, 1 year, and 5 years postoperatively. At each follow-up point, the visual analogue score (VAS) for knee pain, Hospital for Special Surgery (HSS) score, Forgotten Joint Score (FJS-12), and MOS item short-form health survey (SF-36) were assessed. Results:All 613 patients were successfully followed up, with a follow-up period of 5.25±1.02 years (range, 5.0-6.0 years). There were no statistically significant differences in gender, age, BMI, and K-L classification between the two groups ( P>0.05). The differences in postoperative varus angle, VAS scores, and HSS score were statistically significant from the preoperative values in both groups( P<0.05). The surgical duration of the retained varus group was 77.40±18.55 min, total blood loss was 920.78±407.26 ml, and lower limb swelling on the fifth postoperative day was 1.18±0.51 cm, all of which were lower than those in the mechanical alignment group: 85.31±22.15 min, 1127.14±580.08 ml, 3.22±0.52 cm, respectively, with statistically significant differences ( P<0.05). The VAS scores at postoperative day 5 and 3 months in the retained varus group were 5.08±0.72 and 2.18±1.09, respectively, which were lower than those in the mechanical alignment group: 5.80±0.81, 3.00±1.04, with statistically significant differences ( P<0.05). There were no statistically significant differences in VAS scores at 6 months, 1 year, and 5 years postoperatively between the two groups ( P>0.05). The HSS scores at 3 months and 6 months postoperatively in the retained varus group were 68.57±4.98 and 79.04±3.26, respectively, which were higher than those in the mechanical alignment group: 64.14±3.99, 77.73±4.04, with statistically significant differences ( P<0.05). There were no statistically significant differences in HSS scores at 1 year and 5 years postoperatively between the two groups ( P>0.05). The FJS-12 scores at 3 months and 6 months postoperatively in the retained varus group were 18.06±3.50 and 27.50±1.80, respectively, which were higher than those in the mechanical alignment group: 13.45±2.44, 24.23±1.59, with statistically significant differences ( P<0.05). There were no statistically significant differences in FJS-12 scores at 1 year and 5 years postoperatively between the two groups ( P>0.05). The SF-36 scores at 3 months and 6 months postoperatively in the retained varus group were 40.85±8.07 and 52.15±6.01, respectively, which were higher than those in the mechanical alignment group: 35.87±6.83, 47.28±5.38, with statistically significant differences ( P<0.05). There were no statistically significant differences in SF-36 scores at 1 year and 5 years postoperatively between the two groups ( P>0.05). The incidence of deep vein thrombosis in the lower limbs was 3.8% (12/318) in the retained varus group, which was lower than the 7.8% (23/295) in the mechanical alignment group, with a statistically significant difference ( P<0.05). Conclusion:In osteoarthritis patients with moderate knee varus undergoing TKA, retaining approximately 3° of varus can reduce surgical trauma and total blood loss, shorten surgical duration, alleviate postoperative pain and limb swelling, facilitate functional recovery, and improve patient satisfaction.
7.Correlation between serum cystatin C and bone turnover markers in elderly patients with type 2 diabetes mellitus and osteoporosis
Mengqian WANG ; Shaohong ZHANG ; Mengyue SUN ; Min CHEN ; Weimin WANG
Journal of Public Health and Preventive Medicine 2025;36(4):89-92
Objective To analyze the correlation between serum cystatin C (Cys-C) and bone turnover markers in elderly patients with type 2 diabetes mellitus (T2DM) and osteoporosis. Methods A retrospective analysis was conducted on the data of 320 elderly patients with T2DM admitted to Huai'an First People's Hospital from August 2021 to June 2024. Patients were divided into the osteoporosis group and the non-osteoporosis group according to whether they had osteoporosis. General information, bone turnover markers, and serum Cys-C levels were collected from all patients. The data were compared between the two groups to analyze the influencing factors of osteoporosis in elderly patients with T2DM and the correlation between serum Cys-C and bone turnover markers. Results The levels of total cholesterol and LDL-C in the osteoporosis group were higher than those in the non-osteoporosis group, and the bone mineral density was lower than that in the non-osteoporosis group (P<0.05). The levels of TPINP, β-CTX, and Cys-C in the osteoporosis group were higher than those in the non-osteoporosis group, and 25-OH-D3 level was lower than that in the non-osteoporosis group (P<0.05). Serum Cys-C was positively correlated with TPINP and β-CTX, and negatively correlated with 25-OH-D3 (P<0.05). Multivariate logistic regression analysis found that total cholesterol, LDL-C, TPINP, β-CTX, 25-OH-D3, and Cys-C were factors influencing osteoporosis in elderly patients with T2DM (P<0.05). Conclusion Serum Cys-C levels in elderly patients with T2DM and osteoporosis are elevated. There is a significant correlation between Cys-C level and bone turnover markers.
8.NIR-II-activated whole-cell vaccine with ultra-efficient semiconducting diradical oligomers for breast carcinoma growth and metastasis inhibition.
Yijian GAO ; Yachao ZHANG ; Yujie MA ; Xiliang LI ; Yu WANG ; Huan CHEN ; Yingpeng WAN ; Zhongming HUANG ; Weimin LIU ; Pengfei WANG ; Lidai WANG ; Chun-Sing LEE ; Shengliang LI
Acta Pharmaceutica Sinica B 2025;15(2):1159-1170
High-performance phototheranostics with combined photothermal therapy and photoacoustic imaging have been considered promising approaches for efficient cancer diagnosis and treatment. However, developing phototheranostic materials with efficient photothermal conversion efficiency (PCE), especially over the second near-infrared window (NIR-II, 1000-1700 nm), remains challenging. Herein, we report an ultraefficient NIR-II-activated nanomedicine with phototheranostic and vaccination capability for highly efficient in vivo tumor elimination and metastasis inhibition. The NIR-II nanomedicine of a semiconducting biradical oligomer with a motor-flexible design was demonstrated with a record-breaking PCE of 87% upon NIR-II excitation. This nanomedicine inherently features extraordinary photothermal stability, good biocompatibility, and excellent photoacoustic performance, contributing to high-contrast photoacoustic imaging in living mice and high-performance photothermal elimination of tumors. Moreover, a whole-cell vaccine based on a NIR-II nanomedicine with NIR-II-activated performance was further designed to remotely activate the antitumor immunologic memory and effectively inhibit tumor occurrence and metastasis in vivo, with good biosafety. Thus, this work paves a new avenue for designing NIR-II active semiconducting biradical materials as a promising theranostics platform and further promotes the development of NIR-II nanomedicine for personalized cancer treatment.
9.Impact of early antimicrobial therapy on clinical outcomes in patients with suspected sepsis in emergency and outpatient settings: a prospective cohort study.
Xianxian XU ; Hongqing SHEN ; Weimin ZHU ; Ping LI ; Peng YANG ; Renfei SHAN ; Nanjin CHEN ; Yongpo JIANG
Chinese Critical Care Medicine 2025;37(4):337-342
OBJECTIVE:
To investigate the impact of early antimicrobial therapy on the prognosis of patients with suspected sepsis in emergency and outpatient settings.
METHODS:
A prospective cohort study was conducted. Patients with suspected sepsis admitted to the emergency department of Taizhou Hospital, Zhejiang Province, from May 1, 2022, to July 31, 2023, were enrolled. Participants were divided into an early group (0-1 hour) and a delayed group (> 1 hour) according to duration from admission to antimicrobial administration. General information, initial vital signs, laboratory parameters within 24 hours after admission, disease severity scores, vasoactive drug usage, and clinical outcomes of the patient were collected. Kaplan-Meier survival curve was used to analyze 28-day survival. Multivariate Cox proportional hazards regression was performed to identify independent risk factors for prognosis of the patients with suspected sepsis in emergency and outpatient settings. Sensitivity analyses were conducted through subgroup analyses.
RESULTS:
A total of 143 patients with suspected sepsis were enrolled in the analysis, with 66 patients in the early group and 77 in the delayed group. No statistically significant differences were observed in baseline characteristics (age, gender, vital signs, laboratory parameters, disease severity scores) or clinical outcomes [vasoactive drug usage rate, mechanical ventilation duration, length of intensive care unit (ICU) stay, total hospitalization duration] between the two groups. The 28-day mortality, multidrug resistance rate and sepsis confirmation rate did not differ significantly between the early group and delay group [28-day mortality: 18.2% (12/66) vs. 20.8% (16/77), multidrug resistance rate: 3.0% (2/66) vs. 2.6% (2/77), sepsis confirmation rate: 87.9% (58/66) vs. 88.3% (68/77), all P > 0.05]. Kaplan-Meier survival curve analysis showed no difference in 28-day cumulative survival between the two groups (Log-Rank test: χ2 = 2.528, P = 0.112). Multivariate Cox proportional hazards regression identified vasoactive drug usage [hazard ration (HR) = 2.465, 95% confidence interval (95%CI) was 1.019-5.961, P = 0.045] and endotracheal intubation (HR = 5.516, 95%CI was 2.195-13.858, P < 0.001) as independent risk factors for 28-day death of the patients with suspected sepsis in emergency and outpatient settings. Further exploration of the impact of early antimicrobial therapy on 28-day death in different subgroups of the patients with suspected sepsis in emergency and outpatient settings was conducted through subgroup analysis. The results showed that in the patients with different ages (< 60 years old: HR = 1.214, 95%CI was 0.535-2.751, P = 0.643; ≥ 60 years old: HR = 2.085, 95%CI was 0.233-18.668, P = 0.511), sequential organ failure assessment (SOFA) scores (< 6: HR = 1.411, 95%CI was 0.482-4.128, P = 0.530; ≥ 6: HR = 0.869, 95%CI was 0.292-2.587, P = 0.801), shock indexes (< 1: HR = 1.095, 95%CI was 0.390-3.077, P = 0.863; ≥ 1: HR = 1.364, 95%CI was 0.458-4.059, P = 0.577) and whether diagnosed with sepsis or not (yes: HR = 0.943, 95%CI was 0.059-15.091, P = 0.967; no: HR = 1.207, 95%CI was 0.554-2.628, P = 0.636) subgroups, early usage of antibiotics had not shown any advantage in improving prognosis compared with delayed usage.
CONCLUSION
Early antimicrobial therapy does not improve the prognosis of patients with suspected sepsis in emergency and outpatient settings.
Humans
;
Sepsis/drug therapy*
;
Prospective Studies
;
Prognosis
;
Emergency Service, Hospital
;
Outpatients
;
Female
;
Male
;
Anti-Infective Agents/therapeutic use*
;
Middle Aged
;
Aged
;
Proportional Hazards Models
;
Treatment Outcome
10.Proteomics reveals biomarkers for sepsis-associated acute kidney injury: a prospective multicenter cohort study.
Weimin ZHU ; Nanjin CHEN ; Hanzhi DAI ; Cuicui DONG ; Yubin XU ; Qi CHEN ; Fangyu YU ; Cheng ZHENG ; Chao ZHANG ; Sheng ZHANG ; Yinghe XU ; Yongpo JIANG
Chinese Critical Care Medicine 2025;37(8):707-714
OBJECTIVE:
To identify and validate novel biomarkers for the early diagnosis of sepsis-associated acute kidney injury (SA-AKI) and precise continuous renal replacement therapy (CRRT) using proteomics.
METHODS:
A prospective multicenter cohort study was conducted. Patients with sepsis admitted to five hospitals in Taizhou City of Zhejiang Province from April 2019 to December 2021 were continuously enrolled, based on the occurrence of acute kidney injury (AKI). Sepsis patients were divided into SA-AKI group and non-SA-AKI group, and healthy individuals who underwent physical examinations during the same period were used as control (NC group). Peripheral blood samples from participants were collected for protein mass spectrometry analysis. Differentially expressed proteins were identified, and functional enrichment analysis was conducted on these proteins. The levels of target proteins were detected by enzyme linked immunosorbent assay (ELISA), and the predictive value of target protein for SA-AKI were evaluated by receiver operator characteristic curve (ROC curve). Additionally, sepsis patients and healthy individuals were selected from one hospital to externally verify the expression level of the target protein and its predictive value for SA-AKI, as well as the accuracy of CRRT treatment.
RESULTS:
A total of 37 patients with sepsis (including 19 with AKI and 18 without AKI) and 31 healthy individuals were enrolled for proteomic analysis. Seven proteins were identified with significantly differential expression between the SA-AKI group and non-SA-AKI group: namely cystatin C (CST3), β 2-microglobulin (β 2M), insulin-like growth factor-binding protein 4 (IGFBP4), complement factor I (CFI), complement factor D (CFD), CD59, and glycoprotein prostaglandin D2 synthase (PTGDS). Functional enrichment analysis revealed that these proteins were involved in immune response, complement activation, coagulation cascade, and neutrophil degranulation. ELISA results demonstrated specific expression of each target protein in the SA-AKI group. Additionally, 65 patients with sepsis (38 with AKI and 27 without AKI) and 20 healthy individuals were selected for external validation of the 7 target proteins. ELISA results showed that there were statistically significant differences in the expression levels of CST3, β 2M, IGFBP4, CFD, and CD59 between the SA-AKI group and non-SA-AKI group. ROC curve analysis indicated that the area under the curve (AUC) values of CST3, β 2M, IGFBP4, CFD, and CD59 for predicting SA-AKI were 0.788, 0.723, 0.723, 0.795, and 0.836, respectively, all exceeding 0.7. Further analysis of patients who underwent CRRT or not revealed that IGFBP4 had a good predictive value, with an AUC of 0.84.
CONCLUSIONS
Based on proteomic analysis, CST3, β 2M, IGFBP4, CFD, and CD59 may serve as potential biomarkers for the diagnosis of SA-AKI, among which IGFBP4 might be a potential biomarker for predicting the need for CRRT in SA-AKI patients. However, further clinical validation is required.
Humans
;
Sepsis/complications*
;
Acute Kidney Injury/blood*
;
Proteomics
;
Prospective Studies
;
Biomarkers/blood*
;
Male
;
Female
;
beta 2-Microglobulin/blood*
;
Middle Aged
;
Cystatin C/blood*
;
Aged


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