1.Influence of Footwear on Foot Comfort of Workers Engaged in Prolonged Standing Occupations: A Systematic Review
Lu-ping KANG ; Tai-sheng GONG ; Xiao-hong QUAN ; Chen ZHANG
Safety and Health at Work 2026;17(1):24-32
Prolonged standing work can lead to various lower limb health issues. Footwear, as a convenient and noninvasive intervention, plays a key role in foot protection. The purpose of this review was to evaluate the impact of footwear characteristics on foot comfort among workers engaged in prolonged standing occupations. A systematic search of PubMed, Web of Science, Scopus, and the Cochrane Library was conducted until March 2025 for experimental and observational studies; the review is registered in International Prospective Register of Systematic Reviews (CRD420251003253).Given the diversity of study designs, participant characteristics, and outcome measures, results were synthesized narratively, organizing findings by footwear design factors. The synthesis indicated that soft soles reduce foot impact and fatigue but offer limited support, whereas hard soles enhance stability but may cause localized pressure and discomfort. Sole hardness should balance cushioning and support based on activity: hard soles for standing and soft soles for walking. Insole hardness must be carefully considered as semirigid arch supports can cause discomfort. Most insoles improve pressure distribution by adjusting arch loading, and some enhance intrinsic foot muscles by promoting toe engagement, reducing leg swelling. Custom orthotic insoles outperform standard ones in comfort and balance. Future research should promote interdisciplinary collaboration with footwear designers to explore key design parameters and establish a scientific framework for protective footwear.
2.Potential molecular mechanism of lncRNAs HOTAIR in malignant metastasis of esophageal cancer.
Kaijin LU ; Jiangfeng SHEN ; Guang HAN ; Quan CHEN
Chinese Journal of Cellular and Molecular Immunology 2025;41(3):236-244
Objective To elucidate the molecular mechanism by which exosomes (Exo) derived from cancer-associated fibroblasts (CAF) carrying HOX transcript antisense intergenic RNA (lncRNA HOTAIR) promote the metastasis of esophageal squamous cell carcinoma (ESCC). Methods CAFs were collected from tumor tissues, and non-cancer associated fibroblasts (NFs) were obtained from adjacent normal tissues at least 5 cm away from the tumor. Exosomes (CAFs-Exo and NFs-Exo) were isolated from conditioned media collected from CAFs or NFs. CAFs-Exo and NFs-Exo were incubated with human ESCC cell line TE-1 for 24 hours, and CCK-8 was used to determine the cell proliferation ability. Scratch test and Transwell test were performed to determine the cell migration and invasion ability. TE-1 cells were divided into the following two groups: NC group and KD group. The NC group and KD group were transfected with control siRNAs or siRNAs targeting HOTAIR respectively. The effects of HOTAIR knock-down on cell proliferation, migration, invasion and glycolysis were determined. Results CAFs-Exo promoted the proliferation of TE-1 cells more significantly than NFs-Exo. Compared with NFs-Exo group, the migration and invasion ability of TE-1 cells treated with CAFs-Exo were improved significantly. In addition, CAFs-Exo treatment inhibited the expression of E-cadherin and enhanced the expression of N-cadherin. The expression of HOTAIR in CAFs was significantly higher than that in NFs. Compared with NFs-Exo, the expression level of HOTAIR in CAFs-Exo increased significantly. Compared with NC group, the proliferation, migration and invasion of TE-1 cells in KD group decreased significantly. Compared with NC group, hexokinase 2 (HK2), extracellular acidification rate (ECAR) and ATP/ADP ratio of TE-1 cells in KD group decreased significantly. Conclusion HOTAIR, an exosome derived from CAFs, may be involved in metastasis and EMT by regulating glycolysis in ESCC cells.
Humans
;
RNA, Long Noncoding/metabolism*
;
Esophageal Neoplasms/metabolism*
;
Cell Movement/genetics*
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Cell Proliferation/genetics*
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Cell Line, Tumor
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Esophageal Squamous Cell Carcinoma
;
Exosomes/genetics*
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Neoplasm Metastasis
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Neoplasm Invasiveness
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Gene Expression Regulation, Neoplastic
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Glycolysis/genetics*
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Cancer-Associated Fibroblasts/metabolism*
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Carcinoma, Squamous Cell/metabolism*
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Cadherins/genetics*
3.Prevalence and risk factors of training-related abdominal injuries: A multicenter survey study.
Chuan PANG ; Wen-Quan LIANG ; Gan ZHANG ; Ting-Ting LU ; Yun-He GAO ; Xin MIAO ; Zhi-Da CHEN ; Yi LIU ; Wen-Tong XU ; Hong-Qing XI
Chinese Journal of Traumatology 2025;28(4):301-306
PURPOSE:
This study aims to identify the prevalence and risk factors of military training-related abdominal injuries and help plan and conduct training properly.
METHODS:
This questionnaire survey study was conducted from October 2021 to May 2022 among military personnel from 6 military units and 8 military medical centers and participants' medical records were consulted to identify the training-related abdominal injuries. All the military personnel who ever participated in military training were included. Those who refused to participate in this study or provided an incomplete questionnaire were excluded. The questionnaire collected demographic information, type of abdominal injury, frequency, training subjects, triggers, treatment, and training disturbance. Chi-square test and t-test were used to compare baseline information. Univariate and multivariate regression analyses were used to explore the risk factors associated with military training-related abdominal injuries.
RESULTS:
A total of 3058 participants were involved in this study, among which 1797 (58.8%) had suffered training-related abdominal injuries (the mean age was 24.3 years and the service time was 5.6 years), while 1261 (41.2%) had no training-related abdominal injuries (the mean age was 23.1 years and the service time was 4.3 years). There were 546 injured patients (30.4%) suspended the training and 84 (4.6%) needed to be referred to higher-level hospitals. The most common triggers included inadequate warm-up, fatigue, and intense training. The training subjects with the most abdominal injuries were long-distance running (589, 32.8%). Civil servants had the highest rate of abdominal trauma (17.1%). Age ≥ 25 years, military service ≥ 3 years, poor sleep status, and previous abdominal history were independent risk factors for training-related abdominal injury.
CONCLUSION
More than half of the military personnel have suffered military training-related abdominal injuries. Inadequate warm-up, fatigue, and high training intensity are the most common inducing factors. Scientific and proper training should be conducted according to the factors causing abdominal injuries.
Humans
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Military Personnel
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Risk Factors
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Prevalence
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Male
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Abdominal Injuries/etiology*
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Female
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Adult
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Surveys and Questionnaires
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Young Adult
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.Astragaloside IV delayed the epithelial-mesenchymal transition in peritoneal fibrosis by inhibiting the activation of EGFR and PI3K-AKT pathways.
Ying HUANG ; Chen-Ling CHU ; Wen-Hui QIU ; Jia-Yi CHEN ; Lu-Xi CAO ; Shui-Yu JI ; Bin ZHU ; Guo-Kun WANG ; Quan-Quan SHEN
Journal of Integrative Medicine 2025;23(6):694-705
OBJECTIVE:
Peritoneal fibrosis (PF) is an adverse event that occurs during long-term peritoneal dialysis, significantly impairing treatment efficiency and adversely affecting patient outcomes. Astragaloside IV (AS-IV), a principal active component derived from Astragalus membranaceus (Fisch.) Bunge, has exhibited anti-inflammatory and antifibrotic effects in various settings. This study aims to investigate the potential therapeutic efficacy and mechanism of AS-IV in the treatment of PF.
METHODS:
The PF mouse model was established by intraperitoneal injection of 4.25% peritoneal dialysis fluid (100 mL/kg). The epithelial-mesenchymal transition (EMT) of HMrSV5 cells was induced by the addition of 10 ng/mL transforming growth factor β (TGF-β). The differentially expressed genes in HMrSV5 cells treated with AS-IV were screened using transcriptome sequencing analysis. The potential targets of AS-IV were screened using network pharmacology and analyzed using molecular docking and molecular dynamics simulations.
RESULTS:
Administration of AS-IV at doses of 20, 40, or 80 mg/kg effectively mitigated the increase in peritoneal thickness and the development of fibrosis in mice with PF. The expression of the fibrosis marker α-smooth muscle actin in the peritoneum was significantly decreased in AS-IV-treated mice. The treatment of AS-IV (10, 20, and 40 μmol/L) significantly delayed the EMT of HMrSV5 cells induced by TGF-β, as demonstrated by the decreased number of 5-ethynyl-2'-deoxyuridine-positive cells, reduced migrated area, and decreased expression of fibrosis markers. A total of 460 differentially expressed genes were detected in AS-IV-treated HMrSV5 cells through transcriptome sequencing, with notable enrichment in the phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K)-AKT serine/threonine kinase 1 (AKT) signaling pathway. The reduced levels of phosphorylated PI3K (p-PI3K) and p-AKT were detected in HMrSV5 cells with AS-IV treatment. Epidermal growth factor receptor (EGFR) was predicted as a direct target of AS-IV, exhibiting strong hydrogen bond interactions. The activation of the PI3K-AKT pathway by the compound 740Y-P, and the activation of the EGFR pathway by NSC 228155 each partially counteracted the inhibitory effect of AS-IV on the EMT of HMrSV5 cells.
CONCLUSION
AS-IV delayed the EMT process in peritoneal mesothelial cells and slowed the progression of PF, potentially serving as a therapeutic agent for the early prevention and treatment of PF. Please cite this article as: Huang Y, Chu CL, Qiu WH, Chen JY, Cao LX, Ji SY, Zhu B, Wang GK, Shen QQ. Astragaloside IV delayed the epithelial-mesenchymal transition in peritoneal fibrosis by inhibiting the activation of EGFR and PI3K-AKT pathways. J Integr Med. 2025; 23(6):694-705.
Epithelial-Mesenchymal Transition/drug effects*
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Animals
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Saponins/pharmacology*
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Triterpenes/pharmacology*
;
Mice
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Peritoneal Fibrosis/pathology*
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Proto-Oncogene Proteins c-akt/metabolism*
;
ErbB Receptors/metabolism*
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Phosphatidylinositol 3-Kinases/metabolism*
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Signal Transduction/drug effects*
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Male
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Humans
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Molecular Docking Simulation
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Cell Line
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Mice, Inbred C57BL
7.Research Advances in the Construction and Application of Intestinal Organoids.
Qing Xue MENG ; Hong Yang YI ; Peng WANG ; Shan LIU ; Wei Quan LIANG ; Cui Shan CHI ; Chen Yu MAO ; Wei Zheng LIANG ; Jun XUE ; Hong Zhou LU
Biomedical and Environmental Sciences 2025;38(2):230-247
The structure of intestinal tissue is complex. In vitro simulation of intestinal structure and function is important for studying intestinal development and diseases. Recently, organoids have been successfully constructed and they have come to play an important role in biomedical research. Organoids are miniaturized three-dimensional (3D) organs, derived from stem cells, which mimic the structure, cell types, and physiological functions of an organ, making them robust models for biomedical research. Intestinal organoids are 3D micro-organs derived from intestinal stem cells or pluripotent stem cells that can successfully simulate the complex structure and function of the intestine, thereby providing a valuable platform for intestinal development and disease research. In this article, we review the latest progress in the construction and application of intestinal organoids.
Organoids/cytology*
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Intestines/physiology*
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Humans
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Animals
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Pluripotent Stem Cells
8.A controlled study on the efficacy of combined indoor light therapy for depression and its effects on physiological indicators
Li YANG ; Ruojia REN ; Wenting LU ; Tianyu ZHAO ; Shijie GUO ; Bufan LIU ; Fanfan HUANG ; Huan CHEN ; Na JIN ; Yuehang XU ; Quan LIN ; Xueyi WANG
Chinese Journal of Psychiatry 2025;58(3):211-219
Objective:To investigate the efficacy of lightroom therapy on depressive mood and sleep problems in patients with depression, and the potential effects on physiological indices related to circadian rhythms.Methods:From October 2021 to July 2023, 54 patients with acute-phase depression hospitalized in the Mental Health Center of the First Hospital of Hebei Medical University were recruited. The participants were randomly assigned to either medication combined with the bright light therapy group (bright light group, n=36) or medication combined with the dim light therapy group (dim light group, n=18). Both groups received light therapy for 2 weeks, at 10 000 lx in the bright light group and 300 lx in the dim light group. Both groups received 30 minutes of light therapy from 7:30-8:00 a.m daily over two weeks, followed up for 1 week post-treatment. The Hamilton Depression Rating Scale (HAMD 17) was used to assess patients′ depressive symptoms, and the Pittsburgh Sleep Quality Index (PSQI) was used to assess patients′ sleep quality at baseline, at the end of every week. The 32-Item Hypomania Checklist (HCL-32) was used at the end of week 2 to assess the risk of manic switching after treatment. Daily measurements of body temperature, heart rate, and blood pressure were taken before and after light therapy, along with recording adverse events related to the therapy. Paired t- tests were used to compare changes in physiological indicators before and after treatment, and repeated measures ANOVA was applied to compare clinical symptom changes between the two groups. Results:Thirty-one and fifteen patients completed this study in the bright light and dim light groups, respectively, with no statistically significant difference in dropout rates( P>0.05). There were significant interaction effects between the time and group for HAMD 17 and PSQI score( F=5.51,4.11, both P<0.05). Both groups showed significant reductions in HAMD 17 and PSQI scores at baseline, week 1, week 2, and week 3 ( P<0.001). In the bright light group, body temperature increased significantly post-treatment on days 1-4, day 7, and day 12 (all P<0.05). Heart rate elevated on day 5 ( P<0.05).Systolic blood pressure decreased on days 4, 5, 11, and 12 compared to the pre-treatment baseline(all P<0.05). In the dim light group, systolic blood pressure increased on day 11 ( P<0.05). Diastolic blood pressure in the bright light group decreased on days 1, 5, and 6( P<0.05). No serious adverse events, vision loss, ocular structural changes occurred in either group. No hypomania or mania episodes were observed. The incidence of adverse events did not differ significantly ( P>0.05). Conclusion:Medication combined with indoor bright light is more effective than the combination of dim light for depressive symptoms and sleep problems in patients with depression. Patients receiving bright light also may exhibit a higher body temperature, accelerated heart rate, and reduced blood pressure.
9.Efficacy and safety of a facilitated percutaneous coronary intervention with half-dose recombinant staphylokinase in ST-segment elevation myocardial infarction
Tian-yu WU ; Wen-hao ZHANG ; Peng-sheng CHEN ; Chen LI ; Tian WU ; Zhan LÜ ; Tong WANG ; Kun LIU ; Zhi-wen TAO ; Xiao-xuan GONG ; Liang YUAN ; Yong LI ; Bo CHEN ; Xin CHEN ; Zeng-guang CHEN ; Nai-quan YANG ; Yuan-yuan SANG ; Xiao-yan WANG ; Bai-hong LI ; Li ZHU ; Guo-yu WANG ; Xin ZHAO ; Chuan LU ; Jun JIANG ; Rui-na HAO ; Chun-jian LI
Chinese Journal of Interventional Cardiology 2025;33(8):431-438
Objective To investigate the clinical efficacy and safety of facilitated percutaneous coronary intervention(PCI)with half-dose recombinant staphylokinase(r-SAK)in patients with ST-segment elevation myocardial infarction(STEMI)who are expected to undergo PCI within 120 minutes.Methods From October 2021 to August 2022,a total of 200 STEMI patients in eight centers were included and randomly assigned in a 1﹕1 ratio to either r-SAK group or control group.Patients received loading doses of aspirin and ticagrelor and intravenous heparin and were randomized to receive an intravenous bolus of either 5 mg r-SAK or normal saline prior to PCI.The outcomes were set as ST-segment resolution(STR)at 60-90 minutes after PCI,the proportion and transition of pathological Q waves on the 5th day after PCI,and the proportion of high-sensitivity cardiac troponin T(hs-cTnT)peaking within 12 hours of onset.The safety outcome was major bleeding events defined as Bleeding Academic Research Consortium(BARC)≥type 3 bleeding during hospitalization.Results Compared with the control group,the r-SAK group had a higher proportion of STR≥70%within 60-90 minutes after PCI(58.3%vs.40.3%,P=0.009);a lower proportion of pathological Q waves(59.1%vs.74.1%,P=0.040);a lower rate of Q wave progression(14.8%vs.43.2%,P<0.001);a higher rate of Q wave disappearance(12.5%vs.3.7%,P=0.027);and a higher proportion of hs-cTnT peaking within 12 hours of symptom onset[31/40(77.5%)vs.17/33(51.5%),P=0.027].Regarding the safety outcome,no significant difference in BARC≥type 3 bleeding was found between the two groups during hospitalization(P>0.05).Conclusions For STEMI patients who were expected to undergo primary PCI within 120 minutes of symptom onset,the facilitated PCI with half-dose r-SAK significantly increased the proportion of STR≥70%at 60-90 minutes after PCI,reduced the formation of pathological Q waves,and shortened the time to peak hs-cTnT,without increasing the risk of bleeding,which should be an alternative reperfusion strategy worthy of further study.
10.Effects of combined hypoxia and irradiation on mouse bone marrow hematopoietic cells
Xinhai YANG ; Fang CHEN ; Yong QUAN ; Mengjia HU ; Yukai LU ; Naicheng CHEN ; Yang XU ; Song WANG ; Junping WANG
Journal of Army Medical University 2025;47(7):681-690
Objective To determine the effects of hypoxia pre-treatment combined with radiation damage on the hematopoietic cells in the bone marrow of mice.Methods A total of 165 male C57BL/6 mice(10~12 weeks old,weighing 20~25 g)were randomly divided into 7 groups:normal control(Control,n=33),6 Gy irradiation(6-Gy,n=43),7 d hypoxia-6 Gy irradiation(Hy-7 d+6 Gy,n=43),7 Gy irradiation(7 Gy,n=12),7 d hypoxia-7 Gy irradiation(Hy-7 d+7 Gy,n=12),7 Gy continuous hypoxia treatment(Hy-7 d+7 Gy+Hy,n=12),and 6 Gy continuous hypoxia treatment(Hy-7 d+6 Gy+Hy,n=10).The mice of the hypoxia treatment groups were given 7-day hypoxic pretreatment(12%oxygen)in a normobaric hypoxic chamber,while those of the other groups were housed in normoxic condition.After pretreatment,the mice of the irradiation groups were exposed to a single 6 or 7 Gy of whole-body 60Co γ-irradiation in normoxia.The mice of the hypoxia and irradiation groups were kept in hypoxic condition in 24 h post-irradiation followed by being resumed to normoxia,while those of the continuous hypoxia treatment groups were remained in hypoxia.After bone marrow cell suspensions were prepared from the Control,6 Gy,and Hy-7 d+6 Gy groups,bone marrow nucleated cells(BMNCs)were counted via automated cell counter.HE staining was employed to observe pathologic changes in medullary cavity,and flow cytometry was used to assess Lin-Sca1?c-Kit?(LSK)hematopoietic stem/progenitor cells,myeloid progenitors(MPs),and mature T/B/myeloid cells.The mice of the 7 Gy,Hy-7 d+7 Gy,and Hy-7 d+7 Gy+Hy groups were monitored for 30-day survival after hypoxic pretreatment.The dynamic changes in the counts of red blood cells(RBC),white blood cells(WBC)and platelets(PLT),and hemoglobin(HGB)level were observed in the 6 Gy,Hy-7 d+6 Gy,and Hy-7 d+6 Gy+Hy groups with aid of a fully automatic blood analyzer.Single-cell RNA sequencing was performed on bone marrow cell suspension derived from the mice euthanized in 17 d after irradiation from the Control,6 Gy,and Hy-7 d+6 Gy groups.Results ①Compared to the Control group,the 6 Gy group showed significantly reduced BMNCs(P<0.01),dilated bone marrow sinusoids,and erythrocyte extravasation.The Hy-7 d+6 Gy group exhibited higher cellular density and attenuated BMNC loss than the 6 Gy group(P<0.01).②Flow cytometry revealed less LSK,MP,and mature T/B/myeloid cells in the 6 Gy group than the Control group(P<0.05),and the reduced counts of LSK and MP were mitigated in the Hy-7 d+6 Gy group(P<0.01).③The Hy-7 d+7 Gy group demonstrated improved 30-day survival than the 7 Gy group(P<0.01),while continuous hypoxia(Hy-7 d+7 Gy+Hy)failed to enhance the survival.No statistical difference was seen in the survival rate between the 2 groups(P=0.12),though the Hy-7 d+7 Gy group showing higher survival rate.④Routine blood test revealed that the Hy-7 d+6 Gy group showed faster WBC recovery(vs the 6 Gy and Hy-7 d+6 Gy+Hy groups,P<0.05),higher pre-irradiation RBC/HGB levels,and accelerated PLT restoration(P<0.05).⑤Single-cell RNA sequencing indicated that hypoxia pretreatment suppressed the numbers of long-term hematopoietic stem cells/short-term hematopoietic stem cells(LT-HSC/ST-HSC)depletion in the Hy-7 d+6 Gy group when compared with the 6 Gy group,which was consistent with the results of flow cytometry.Pseudotime trajectory aligned the Hy-7 d+6 Gy group,as the Control group,showed enriched undifferentiated LSKs.Differential gene analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)analysis revealed that oxidative phosphorylation pathway was strongly activated in the 6 Gy group,while the Hy-7 d+6 Gy group had enriched in chromatin remodeling and mRNA surveillance pathways.Conclusion Hypoxic preconditioning alleviates radiation-induced bone marrow injury,and post-irradiation normoxia restoration promotes hematopoietic recovery in acute radiation-exposed mice.

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