1.A Mechanistic Framework of Exercise-induced Amelioration of Autism Spectrum Disorder via miR-132, miR-34a, and miR-146a
Xiao YANG ; Ya-Qi XUE ; Xin-Jian SHU ; Yan-Yan WANG ; Niu LIU
Progress in Biochemistry and Biophysics 2026;53(8):2210-2219
Autism spectrum disorder (ASD) is a neurodevelopmental condition with a steadily rising global prevalence, yet effective pharmacological interventions remain notably limited, highlighting an urgent need for safe, accessible, and mechanism-based therapeutic strategies. Physical exercise has emerged as a promising non-pharmacological intervention that ameliorates both core symptoms—social communication deficits and restricted repetitive behaviors—and associated features including cognitive dysfunction and motor impairments, in children and adolescents with ASD. However, the molecular mechanisms mediating these beneficial effects remain incompletely defined, impeding the development of evidence-based exercise prescriptions and biomarker-driven rehabilitation protocols. MicroRNAs (miRNAs) are evolutionarily conserved small non-coding RNAs that post-transcriptionally regulate approximately 60% of protein-coding genes. Within the central nervous system, miRNAs orchestrate diverse neurobiological processes including neural progenitor proliferation, neuronal differentiation, dendritic spine morphogenesis, synaptic plasticity, and neuroinflammatory homeostasis. Notably, miRNAs are remarkably stable in biological fluids and can be packaged into extracellular vesicles, rendering them attractive candidates as both mechanistic mediators and non-invasive peripheral biomarkers. Among the hundreds of miRNAs expressed in the brain, three—miR-132, miR-34a, and miR-146a—have emerged as particularly relevant to ASD pathophysiology. This review focuses on these three miRNAs for the following reasons: miR-132 is a master regulator of activity-dependent synaptic plasticity through its modulation of BDNF/MeCP2/PTEN signaling and has been consistently downregulated in ASD prefrontal cortex; miR-34a functions as a pro-apoptotic factor that suppresses Bcl-2-mediated neuronal survival pathways and is upregulated in ASD cerebellum; and miR-146a serves as a key brake on neuroinflammation via TLR7/IRAK1 signaling and shows region-specific dysregulation in ASD temporal lobe. We first summarize evidence from human post-mortem brain tissues and ASD animal models demonstrating the consistent dysregulation of these three miRNAs. Notably, the pathological consequences of these miRNA alterations—impaired synaptic plasticity, excessive neuronal apoptosis, and sustained neuroinflammation—are interconnected and collectively contribute to the heterogeneous symptomatology of ASD. We then present a synthesis of emerging evidence demonstrating that various exercise modalities, including swimming, treadmill running, and voluntary wheel running, can concurrently reverse these ASD-like behavioral phenotypes and normalize the expression of the three key miRNAs. These data provide the first direct experimental evidence linking exercise-induced miRNA modulation to ASD symptom improvement. On the basis of these findings, we propose an integrative “exercise-miRNA-ASD” framework wherein exercise functions as a multi-targeted modulator—simultaneously enhancing synaptic plasticity, promoting neuronal survival, and attenuating neuroinflammation—through coordinated regulation of the three miRNAs. Importantly, this framework is not merely descriptive but offers testable predictions: exercise-induced miRNA changes should be dose-dependent, show temporal correlation with behavioral improvements, and be blunted by miRNA-specific antagonists or CRISPR/Cas9-mediated knockout. Beyond its specific application to ASD, this framework has broader implications. The miR-132/BDNF, miR-34a/Bcl-2, and miR-146a/TLR7 pathways are not ASD-specific but represent fundamental neural stress and repair mechanisms that are dysregulated across Alzheimer’s disease (AD), traumatic brain injury, Parkinson’s disease (PD), and major depressive disorder. Exercise has been shown to modulate these same miRNAs in several of these conditions, suggesting that the “exercise-miRNA-neural function” axis may represent a conserved neuroprotective mechanism that transcends diagnostic boundaries. Thus, we propose that ASD serves as an ideal model disease for elucidating this universal mechanism, with findings potentially generalizable to other neurological disorders. We also critically evaluate current translational barriers: the near-absence of human clinical trials with serial miRNA profiling; the undefined dose-response relationships between exercise parameters and miRNA expression; the unresolved causality issue (current evidence demonstrates association, not causation); and the uncertain correlation between peripheral exosomal miRNA levels and brain miRNA dynamics. We argue that future research must prioritize CRISPR/Cas9-based miRNA manipulation in animal models combined with longitudinal exercise interventions to establish causality, and that cross-disease validation studies are essential to determine whether exercise-induced miRNA changes represent a shared neuroprotective signature or disease-specific responses. Ultimately, we envision a paradigm where a simple blood test measuring exosomal miR-132, miR-34a, and miR-146a levels could guide personalized exercise prescriptions, enabling precision rehabilitation for individuals with ASD and potentially other neurological conditions.
2.Research progress on outdoor wet bulb globe temperature prediction models and their application to early warning for occupational heat stress
Xiaojun ZHANG ; Luyang WANG ; Xin SUI ; Xiaoshun WANG ; Tian LAN ; Yun ZHENG ; Dongsheng NIU ; Xiaowen DING
Journal of Environmental and Occupational Medicine 2026;43(8):1032-1038
In the context of global warming, protecting outdoor workers from occupational heat exposure has become an important public health concern. This review summarized the principle, applicability, and limitation of three categories of wet bulb globe temperature (WBGT) prediction models: empirical regression models, heat-balance models, and machine-learning models. Drawing on international experience from the United States, Europe, and Japan, this review further examined the technical challenges of applying WBGT-based prediction models to large-scale occupational heat stress early warning systems. In response to gaps in occupational heat stress management in China, WBGT should be considered a core assessment indicator to support a transition from passive response to proactive intervention. A localized implementation pathway is proposed, incorporating mechanism-based model calibration, regional parameter adaptation, and multi-source data fusion. Strengthening collaboration between public health and meteorological departments and developing platform-based flexible intervention strategies for workers in new forms of employment may improve the targeting of occupational heat stress early warning and health protection. Future research should focus on physics-constrained machine learning, refined microenvironmental prediction, and individualized risk assessment to support the development of a digitally enabled occupational heat-health protection framework.
3.Analysis of the association mechanisms between rule adjustment and change in selection outcomes of the national centralized drug procurement with volume-based purchasing program for insulin
Biao WANG ; Qingwei TANG ; Xin JIANG ; Junyu NIU ; Yun JIA ; Tiantian ZHANG
China Pharmacy 2026;37(19):2491-2495
OBJECTIVE To provide evidence for further improving the rules governing the renewal round of national centralized drug procurement with volume-based purchasing (VBP) program for insulin.METHODS Based on publicly available policy documents, selection outcomes, and interview data, policy text analysis, descriptive statistical analysis, the Wilcoxon signed-rank test, and thematic analysis were used to compare the procurement rules and selection outcomes between the initial and renewal rounds of the national VBP programs for insulin, and to examine the mechanisms linking rule adjustments to changes in selection outcomes.RESULTS Compared with the initial round, the renewal round retained the six procurement groups and 11 bidding units, reduced the maximum valid bid price by 40%, and introduced competitive bidding selection, revival selection, and a price line for Category A products. A total of 42 products were selected in the initial round and 49 in the renewal round, including 37 that remained selected, 5 that exited, and 12 that were newly selected in the renewal round. Within the same procurement groups, the price range decreased significantly in the renewal round compared with the initial round ( P =0.031), whereas the difference in average price between the two was not statistically significant ( P =0.063). Domestic manufacturers were more likely to enter the A1 category, whereas multinational manufacturers were more likely to remain in categories B/C. Mechanism analysis suggested that the price line shaped the boundary of selected prices, while the classification and volume-allocation rules linked manufacturers’ bidding decisions to expected procurement volumes, potentially altering bidding incentives and corresponding to changes in the distribution of selection outcomes.CONCLUSIONS The renewal round of the insulin VBP program established an interrelated mechanism involving price boundaries, volume-based incentives, and supply constraints through the use of price lines, product classification, and contracted volume allocation. These rule adjustments corresponded to changes in the structure of selected products, price distributions, and manufacturer classifications. Future policy refinement should strengthen the coordination among reasonable price ranges, volume-based incentives, and supply performance.
4.Risk factors for lymph node metastasis after RARP in high-risk prostate cancer patients and construction of a nomogram
Qi CAI ; Ziyan AN ; Zhoujie YE ; Jinpeng SHAO ; Kaipeng BI ; Zheng WANG ; Guanqiu CHEN ; Jie ZHU ; Guangfu CHEN ; Shaoxi NIU ; Baojun WANG ; Xin MA ; Jiangping GAO ; Weijun FU
Chinese Journal of Urology 2025;46(8):593-599
Objective:This study investigated the independent risk factors for lymph node metastasis(LNM)in high-risk prostate cancer(HRPCa)patients undergoing robot-assisted radical prostatectomy(RARP),and constructed a nomogram model based on clinical data to improve the accuracy and clinical practicality of preoperative prediction of LNM.Methods:A retrospective analysis was conducted on the clinical data of 218 HRPCa patients who received RARP treatment at the First Medical Center of the PLA General Hospital from January 2020 to March 2025 as the modeling group. The age of the modeling group was(66.91±6.94)years old. 75 cases(34.40%)had a history of smoking,and 48 cases(22.02%)had a history of drinking. There were a body mass index(BMI)of 25.55(23.58,27.00)kg/m 2,a total prostate-specific antigen(tPSA)of 20.59(10.42,30.61)ng/ml,a free prostate-specific antigen(fPSA)of 1.87(1.04,3.26)ng/ml,a prostate volume(PV)of(41.19±21.00)ml,a prostate-specific antigen density(PSAD)of 0.52(0.30,0.84)ng/ml 2. Among the patients,60 cases(27.52%)had a preoperative biopsy Gleason score >8,and the percentage of positive biopsy cores(PPBC)was 50%(31%,80%). Thirty-one patients(14.22%)were staged clinically as >T 2c. The diagnostic criteria for high-risk prostate cancer(HRPCa)were defined as meeting any one of the following:PSA >20 ng/ml,Gleason score on prostate biopsy ≥8,or clinical stage ≥T 3. Among the 218 patients in the modeling cohort,67 cases(30.73%)met two of the criteria,and 7 cases(3.21%)met all three criteria. All 218 patients underwent RARP,and based on postoperative pathology,they were divided into the LNM group and the non-LNM group. The relationship between the number of diagnostic criteria met and the occurrence of LNM was analyzed. An external validation cohort included 42 HRPCa patients who underwent RARP at the Third,Fifth Medical Centers of the PLA General Hospital between January 2023 and May 2025. Their mean age was(66.79±5.92)years. Eighteen patients(42.86%)had a smoking history,and nine(21.43%)had a history of alcohol consumption. The median BMI was 26.00(23.80,27.13)kg/m 2. The median tPSA level was 17.34(8.97,27.30)ng/ml. The median fPSA was 1.51(0.83,2.52)ng/ml,and the median PV was(35.57 ± 15.25)ml. The median PSAD was 0.57(0.23,0.87)ng/ml 2,and the median PPBC was 58%(36%,71%). Three patients(7.14%)had a clinical stage >T 2c,and 12 patients(28.57%)had a Gleason score >8 on preoperative biopsy. Univariate and multivariate binary logistic regression analyses were used to identify independent risk factors for LNM,and a nomogram model was constructed based on these factors. The predictive performance of the model was evaluated using receiver operating characteristic(ROC)curves and calibration plots,and the model was validated in the external cohort. Result:According to postoperative pathology,45 patients were classified into the LNM group,and 173 into the non-LNM group. The probability of LNM increased proportionally with the number of diagnostic criteria met for HRPCa(meeting two criteria: OR = 4.762,95% CI 2.323-9.761, P < 0.01;meeting three criteria: OR = 10.667,95% CI 2.187-52.025, P=0.003). Binary logistic regression analysis revealed that age( OR=0.913,95% CI 0.859-0.971, P = 0.004),tPSA( OR=1.039,95% CI 1.018-1.061, P<0.01),PPBC( OR = 5.656,95% CI 1.101-29.056, P = 0.038),and clinical T stage(T 2c stage: OR=2.945,95% CI 0.888-9.769, P=0.077;>T 2c stage OR = 18.351,95% CI 4.790-70.306, P < 0.01)were independent risk factors for postoperative LNM in HRPCa patients after RARP. The ROC curve of the nomogram model based on these factors showed an area under the curve(AUC)of 0.853(95% CI 0.790-0.917). In the external validation cohort,the nomogram achieved an AUC of 0.743(95% CI 0.556-0.929). The calibration plots demonstrated good agreement between the predicted probabilities and actual observations. Conclusions:Age,tPSA,PPBC,and clinical T stage were independent predictors of postoperative LNM in HRPCa patients undergoing RARP. The greater the number of HRPCa diagnostic criteria met,the higher the likelihood of postoperative LNM. The nomogram developed in this study could effectively predict the risk of LNM in HRPCa patients after RARP.
5.Survival advantage of first-line chemoimmunotherapy combined with radiotherapy for advanced esophageal squamous cell carcinoma: A propensity score matching analysis
Peixin FENG ; Qing HOU ; Ningning YAO ; Wenjuan ZHANG ; Bochen SUN ; Wenxia NIU ; Anqi ZHAO ; Wenlu CHEN ; Baixue WU ; Yuying ZHOU ; Yiwen ZHANG ; Yu LIANG ; Xin CAO ; Wei BAI ; Jianting LIU ; Shuangping ZHANG ; Jianzhong CAO
Chinese Journal of Radiological Medicine and Protection 2025;45(8):766-773
Objective:To investigate the efficacy of radiotherapy in patients with advanced esophageal cancer receiving first-line chemoimmunotherapy.Methods:A retrospective analysis was conducted on the data of 137 patients with Stage Ⅳ esophageal squamous cell carcinoma (ESCC) treated at our hospital from January 2018 to May 2023. These patients were divided into two groups: a group treated with first-line chemoimmunotherapy combined with radiotherapy (chemoimmunotherapy + radiotherapy group, n = 43) and a group treated with only chemoimmunotherapy ( n = 94). Inverse probability of treatment weighting (IPTW) was applied to balance baseline characteristics between the groups. With overall survival (OS) and progression-free survival (PFS) as study endpoints, the survival data were analyzed using the Kaplan-Meier method, the log-rank test, and the Cox regression method. Results:Before calibration, the chemoimmunotherapy + radiotherapy group significantly outperformed the sole chemoimmunotherapy group in median PFS (13.6 months vs. 7.0 months; HR: 0.501, 95% CI: 0.309-0.811, P = 0.005). After calibration using the COX proportional-hazards model for age, gender, Eastern Cooperative Oncology Group (ECOG) performance status, smoking history, T/N/M stage, and tumor location, the chemoimmunotherapy + radiotherapy group still had significant advantages in PFS (14.7 months vs. 7.0 months; HR: 0.441, 95% CI: 0.261-0.745, P = 0.002). IPTW analysis further confirmed this trend (13.9 months vs. 7.0 months; HR: 0.492, 95% CI: 0.304-0.795, P < 0.001). Specifically, the median OS of the chemoimmunotherapy + radiotherapy group demonstrated significant improvement in all analyses: pre-calibration (29.5 months vs. 18.0 months; HR: 0.507, 95% CI: 0.297-0.867, P = 0.013), after calibration using the Cox model (27.5 months vs. 16.7 months; HR: 0.470, 95% CI: 0.266-0.830, P = 0.009), and after calibration using IPTW (29.5 months vs. 16.9 months; HR: 0.448, 95% CI: 0.262-0.764, P < 0.001). Conclusions:The combination of radiotherapy and first-line chemoimmunotherapy can significantly improve survival outcomes of patients with advanced ESCC, suggesting its potential as a standard treatment strategy.
6.Meta analysis on impact of clinical nursing pathways on parturients with epidural anesthetic analgesia delivery
Jianpei NIU ; Huijie WANG ; Fangli LIU ; Hengli YANG ; Xin DONG ; Yan LI ; Wen XU
Chongqing Medicine 2025;54(9):2158-2164
Objective To systematic evaluate the impact of applying the clinical nursing pathway(CNP)on epidural anesthetic analgesia natural delivery.Methods The randomized controlled trial(RCT)and quasi-experimental researches on the application of CNP in epidural anesthetic analgesia natural delivery were retrieved from PubMed,Cochrane Library,Embase,Web of Science,China Knowledge Network database,Wanfang database,VIP and the Chinese Biomedical Literature Database.The retrieval time limit was from January 1,2014,to July 31,2024 with no language limitation.The meta analysis on the included studies was performed by applying RevMan5.4.1.Results A total of 5 RCTs and 2 quasi-experimental studies were in-cluded,involving 979 parturients with deliveries.The meta analysis showed that compared with the conven-tional nursing,CNP could shorten the duration of the first stage of labor(MD=—1.06,95%CI:—1.95——0.17,P=0.02)and the duration of the second stage of labor(MD=—0.12,95%CI:—0.21——0.03,P=0.006);decreased the rate of perineal lateral incision(RR=0.73,95%CI:0.65-0.83,P<0.001)and inci-dence rate of postpartum urinary retention(RR=0.35,95%CI:0.20-0.63,P<0.001);and shortened the time to lactation initiation(SMD=—1.52,95%CI:—2.38——0.66,P<0.001).There was no influence on reducing postpartum 24 h hemorrhage amount(SMD=—0.51,95%CI:—1.23-0.21,P=0.16).The study subjects were divided into the primipara women subgroup and unclassified parturients subgroup.Compared with the conventional nursing group,compared with the conventional nursing,CNP had no impact on the dura-tion of the first stage of labor(MD=—0.32,95%CI:—0.61-0.98,P=0.63)and the duration of the second stage of labor(MD=—0.11,95%CI:—0.25-0.04,P=0.15)in the primipara women subgroup.CNP could reduce the postpartum 24 h hemorrhage volume in the unclassified parturients subgroup(SMD=—1.47,95%CI:—1.72——1.21,P<0.001).Conclusion Application of CNP in parturients labor analgesia could reduce the perineal lateral incision rate and incidence rate of postpartum urinary retention and shorten the time to lac-tation initiation.Due to the heterogeneity among studies,the impact of CNP on the labor duration and the bleeding amount within postpartum 24 h still requires more high-quality studies to be conducted in the future for verification.
7.Correlation between serum zinc level and prognosis of patients with sepsis
Xiao-Gang WANG ; Jia-Jun MA ; Rui-Xin ZHU ; Li-Bing ZHOU ; Sai-Hu HUANG ; Shui-Yan WU ; Wen-Si NIU ; Jie HUANG ; Zhen-Jiang BAI
Parenteral & Enteral Nutrition 2025;32(5):278-282
Objective:To investigate the differences in clinical outcomes of septic children with varying serum zinc levels,and to analyze the relationship between reduced serum zinc levels and organ dysfunction as well as 28-day mortality in septic children.Methods:This study conducted a retrospective analysis of clinical data from pediatric patients diagnosed with sepsis or septic shock in the Department of critical care medicine of the children's Hospital of Soochow University between January 2017 and December 2022.Clinical characteristics,organ dysfunction,and prognosis were compared between two groups:children with low serum zinc levels and those with normal zinc levels.Results:The serum zinc level of septic children within 24 hours of admission was 9.60(5.52,13.80)μmol/L,with 50.54%(94/186)of the children exhibiting low serum zinc levels(<10.07 μmol/L).Compared to the normal serum zinc group,the low serum zinc group had a significantly lower Pediatric Critical Illness Score(PCIS)[(78.71±9.35)vs.(85.12±8.51),P=0.005]and higher 28-day mortality(46.80%vs.14.13%,P<0.001).The low serum zinc group also had a higher proportion of invasive mechanical ventilation(64.89%vs.47.82%,P=0.019),renal replacement therapy(15.59%vs.3.26%,P=0.003),and use of vasoactive drugs(56.38%vs.30.43%,P<0.001).The rate of underlying conditions in the low serum zinc group was significantly higher than that in the normal serum zinc group(57.44%vs.36.95%,P=0.005).Additionally,the low serum zinc group had a higher incidence of disseminated intravascular coagulation(DIC),respiratory failure,acute kidney injury,shock,and multiple organ dysfunction syndrome(MODS)compared to the normal serum zinc group(P<0.05).Serum zinc levels had predictive value for 28-day mortality in septic children(AUC=0.813;95%CI:0.725~0.902;P<0.001).A serum zinc level of less than 6.950 μmol/L predicted the death of septic children with a sensitivity of 0.618 and a specificity of 0.902.Conclusion:Sepsis in children is commonly associated with low serum zinc levels,especially in those with underlying conditions such as hematologic and oncologic disorders.Sepsis patients hypozincemia with a higher incidence of DIC,respiratory failure,acute kidney injury,shock,and MODS.A serum zinc level below 6.95 μmol/L serves as a significant predictor of 28-day mortality in children with severe sepsis.
8.Meta-analysis of anterior cervical decompression and fusion ROI-CTM self-locking system in treatment of degenerative cervical spondylosis
Yanjie ZHOU ; Chunfeng CAO ; Zhongzu ZHANG ; Xiong NIU ; Xin WANG ; Zaihai YANG ; Liang ZHOU ; Bo LI
Chinese Journal of Tissue Engineering Research 2025;29(3):617-627
OBJECTIVE:Anterior cervical decompression and fusion is a classic surgical method for the treatment of degenerative cervical spondylosis.The use of nail plates increases the fusion rate and stability and indirectly leads to adjacent vertebral degeneration and postoperative dysphagia.In this paper,the clinical results and complications of ROI-CTM self-locking system and traditional cage combined with screw-plate internal fixation in the treatment of degenerative cervical spondylosis were compared by meta-analysis to provide evidence-based support for the selection of internal fixation methods in anterior cervical decompression and fusion. METHODS:CNKI,WanFang,VIP,PubMed,Cochrane Library,Web of Science,and Embase databases were searched for Chinese and English literature on the application of ROI-CTM self-locking system and fusion cage combined with screw plate internal fixation in the treatment of degenerative cervical spondylosis.The retrieval time range was from inception to July 2023.Two researchers selected the literature strictly according to the inclusion and exclusion criteria.The Cochrane bias risk tool was used to evaluate the quality of randomized controlled trials.Newcastle-Ottawa Scale was used to assess the quality of cohort studies.Meta-analysis was performed using RevMan 5.4 software.Outcome indicators included operation time,intraoperative blood loss,Japanese Orthopaedic Association score,Neck Disability Index,C2-C7 Cobb angle,fusion rate,incidence of adjacent vertebral degeneration,cage subsidence rate,and incidence of dysphagia. RESULTS:Thirteen articles were included,including eleven retrospective cohort studies and two randomized controlled trials,with 1 136 patients,569 in the ROI-C group,and 567 in the cage combined with the nail plate group.Meta-analysis results showed that the operation time(MD=-15.52,95%CI:-18.62 to-12.42,P<0.000 01)and intraoperative blood loss(MD=-24.53,95%CI:-32.46 to-16.61,P<0.000 01)in the ROI-C group and the fusion device combined with nail plate group.Postoperative adjacent segment degeneration rate(RR=0.40,95%CI:0.27-0.60,P<0.000 01)and postoperative total dysphagia rate(RR=0.18,95%CI:0.13-0.26),P<0.000 01)were statistically different.The two groups had no significant difference in Japanese Orthopaedic Association score,Neck Disability Index,C2-C7 Cobb angle,fusion rate,or cage subsidence rate(P≥0.05). CONCLUSION:Applying an ROI-CTM self-locking system and traditional cage combined with plate internal fixation in anterior cervical decompression and fusion can achieve satisfactory clinical results in treating degenerative cervical spondylosis.The operation of the ROI-CTM self-locking system is more straightforward.Compared with a cage combined with plate internal fixation,the ROI-CTM self-locking system can significantly reduce the operation time and intraoperative blood loss and has obvious advantages in reducing the incidence of postoperative dysphagia and adjacent segment degeneration.The ROI-CTM self-locking system is recommended for patients with skip cervical spondylosis and adjacent vertebral disease.However,given its possible high settlement rate,using a fusion cage combined with screw-plate internal fixation is still recommended for patients with degenerative cervical spondylosis with multiple segments and high-risk factors of fusion cage settlement,such as osteoporosis and vertebral endplate damage.
9.Two-dimensional black phosphorus materials for bone tissue engineering
Jiahan CHEN ; Chao FENG ; Xiaoxia HUANG ; Minghui NIU ; Xin WANG ; Yong TENG
Chinese Journal of Tissue Engineering Research 2025;29(10):2124-2131
BACKGROUND:Black phosphorus has a high degree of homology with human bone,so it has been extensively studied in the field of bone tissue engineering in recent years.Since 2014,two-dimensional black phosphorus materials have garned significant attention in the field of biomedicine due to their excellent exceptional physical,chemical,and biological properties. OBJECTIVE:To summarize the advancements made in black phosphorus-based nanomaterials for bone tissue engineering,focus on the synthesis methods,osteogenic characteristics,and applications in biomaterials pertaining to two-dimensional black phosphorus nanomaterials. METHODS:Chinese and English key words were"black phosphorus,bone tissue engineering,bone defect,bone regeneration,osteogenesis."Relevant articles in PubMed and CNKI databases from January 2014 to December 2023 were searched.After exclusion and screening,96 articles were analyzed. RESULTS AND CONCLUSION:Black phosphorus nanomaterials play an important role in bone tissue engineering due to their good biocompatibility,biodegradability,photothermal action,antibacterial ability,drug loading performance,and special osteogenic effect,and are ideal candidate materials for promoting bone regeneration.The preparation of black phosphorus nanomaterials is mainly a top-down top-layer stripping method.The main principle is to weaken the van der Waals force between the black phosphorus layers by physical or chemical means to obtain a single or less layer of phosphanse,that is,black phosphorus nanosheets or quantum dots.Black phosphate-based nanocomposites are mainly divided into hydrogels,3D printing scaffolds,composite scaffolds,electrospinning,bionic periosteum,microspheres,and bionic coatings.The research of nano-black phosphorus in bone tissue engineering is in its infancy,and still faces many challenges:the behavior of black phosphorus in vivo and the interaction mechanism with various biomolecules need to be further studied.The long-term potential toxicity of black phosphorus is unknown.The manufacturing process for black phosphorus is difficult to control.Therefore,how to develop uniform size,safe,reliable,and efficient nano black phosphorus and transform it into clinical application requires interdisciplinary research on modern biomedical technology,physicochemical technology,and precision manufacturing technology.
10.Stir-fried Semen Armeniacae Amarum Suppresses Aristolochic Acid I-Induced Nephrotoxicity and DNA Adducts.
Cheng-Xian LI ; Xiao-He XIAO ; Xin-Yu LI ; Da-Ke XIAO ; Yin-Kang WANG ; Xian-Ling WANG ; Ping ZHANG ; Yu-Rong LI ; Ming NIU ; Zhao-Fang BAI
Chinese journal of integrative medicine 2025;31(2):142-152
OBJECTIVE:
To investigate the protective effects of stir-fried Semen Armeniacae Amarum (SAA) against aristolochic acid I (AAI)-induced nephrotoxicity and DNA adducts and elucidate the underlying mechanism involved for ensuring the safe use of Asari Radix et Rhizoma.
METHODS:
In vitro, HEK293T cells overexpressing Flag-tagged multidrug resistance-associated protein 3 (MRP3) were constructed by Lentiviral transduction, and inhibitory effect of top 10 common pairs of medicinal herbs with Asari Radix et Rhizoma in clinic on MRP3 activity was verified using a self-constructed fluorescence screening system. The mRNA, protein expressions, and enzyme activity levels of NAD(P)H quinone dehydrogenase 1 (NQO1) and cytochrome P450 1A2 (CYP1A2) were measured in differentiated HepaRG cells. Hepatocyte toxicity after inhibition of AAI metabolite transport was detected using cell counting kit-8 assay. In vivo, C57BL/6 mice were randomly divided into 5 groups according to a random number table, including: control (1% sodium bicarbonate), AAI (10 mg/kg), stir-fried SAA (1.75 g/kg) and AAI + stir-fried SAA (1.75 and 8.75 g/kg) groups, 6 mice in each group. After 7 days of continuous gavage administration, liver and kidney damages were assessed, and the protein expressions and enzyme activity of liver metabolic enzymes NQO1 and CYP1A2 were determined simultaneously.
RESULTS:
In vivo, combination of 1.75 g/kg SAA and 10 mg/kg AAI suppressed AAI-induced nephrotoxicity and reduced dA-ALI formation by 26.7%, and these detoxification effects in a dose-dependent manner (P<0.01). Mechanistically, SAA inhibited MRP3 transport in vitro, downregulated NQO1 expression in vivo, increased CYP1A2 expression and enzymatic activity in vitro and in vivo, respectively (P<0.05 or P<0.01). Notably, SAA also reduced AAI-induced hepatotoxicity throughout the detoxification process, as indicated by a 41.3% reduction in the number of liver adducts (P<0.01).
CONCLUSIONS
Stir-fried SAA is a novel drug candidate for the suppression of AAI-induced liver and kidney damages. The protective mechanism may be closely related to the regulation of transporters and metabolic enzymes.
Aristolochic Acids/toxicity*
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Animals
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Humans
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NAD(P)H Dehydrogenase (Quinone)/genetics*
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HEK293 Cells
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Kidney/pathology*
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Cytochrome P-450 CYP1A2/genetics*
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Mice, Inbred C57BL
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DNA Adducts/drug effects*
;
Male
;
Kidney Diseases/drug therapy*
;
Drugs, Chinese Herbal/therapeutic use*
;
Mice
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Prunus armeniaca
;
Plant Extracts

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