1.Research on the screening efficiency of Thalassemia based on an automated evaluation software.
Jun HU ; Huan LIANG ; Limei DUAN ; Jianqiang GAO
Chinese Journal of Medical Genetics 2026;43(4):281-287
OBJECTIVE:
To explore the efficacy of a Thalassemia risk assessment software for the screening of thalassemia mutation carriers and distribution of thalassemia genotypes detected by screening.
METHODS:
A total of 6 040 individuals were evaluated at Leshan Maternal and Child Health Care Hospital between 2022 and 2024 using the commonly used clinical thalassemia risk assessment method and the thalassemia screening software, respectively, and the performance indicators of the two methods were compared and analyzed against the result of thalassemia gene testing. This study was approved by the Ethics Committee of our hospital (Ethics No.: LfyLL[2022]005).
RESULTS:
The high-risk rate by the thalassemia screening software was 11.19%, with a sensitivity of 95.12%, specificity of 93.28%, positive predictive value of 43.20%, negative predictive value of 99.72%, and the area under the ROC curve (AUC) was 0.942. The thalassemia gene detection rate of the high-risk samples screened was 4.83%. The high-risk screening rate of the conventional method was 2.50%, with a sensitivity of 51.22%, specificity of 93.28%, positive predictive value of 80.79%, negative predictive value of 97.40%, and the AUC was 0.754. The thalassemia gene detection rate of the high-risk samples was 2.02%.
CONCLUSION
The software can effectively detect thalassemia carriers and significantly reduce the missed detection compared with conventional method, thereby significantly improve the efficacy of screening.
Humans
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Thalassemia/diagnosis*
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Software
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Female
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Genetic Testing/methods*
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Male
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Mutation
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Adult
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Genotype
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ROC Curve
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Risk Assessment
2.Mechanism of Yiqi Huoxue Therapy Regulating IL-33/ST2/IL-1RAP to Improve Nasal Mucosal Tissue Remodeling and Intervene in Allergic Rhinitis
Huan WANG ; Hongping LUO ; Meiya WANG ; Yuyin LIU ; Chenlin WANG ; Chao LIAO ; Fangqi LIANG ; Peizheng XIONG ; Li TIAN
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(14):298-307
ObjectiveTo explore the mechanism by which Qidan Yifei Tongqiao granules (QDYF) alleviate nasal mucosal remodeling in allergic rhinitis (AR) via the interleukin-33 (IL-33)/growth stimulation expressed gene 2 (ST2)/interleukin-1 receptor accessory protein (IL-1RAP) signaling pathway from the perspective of Qi-replenishing and blood-activating therapy. MethodsFirst, according to the previous network pharmacology results, this study predicted the potential mechanisms of QDYF in treating AR by screening key pathways, components, and targets. Molecular docking was performed via AutoDock and PyMOL 2.5.5. Subsequently, a rat model of ovalbumin (OVA)-induced AR was used for validation through in vivo experiments. Forty-eight rats were assigned into 6 groups: Control, model, low-dose QDYF (QDYF-L, 4.04 g·kg-1), medium-dose QDYF (QDYF-M, 8.08 g·kg-1), high-dose QDYF (QDYF-H, 16.16 g·kg-1), and loratadine (0.9 mg·kg-1). After 14 days of intervention, behavioral scores of the rats were observed. The morphological changes of nasal mucosa tissue were observed by hematoxylin-eosin (HE) staining. Masson staining was used to observe collagen fiber deposition in the nasal mucosal tissue and to calculate the collagen volume fraction (CVF). The expression of E-cadherin (E-cad) in the nasal mucosa tissue was detected by immunofluorescence. The serum levels of helper T cell 2 (Th2) cytokines interleukin-4 (IL-4), interleukin-5 (IL-5), and interleukin-13 (IL-13) as well as helper T cell 1 (Th1) cytokines interleukin-2 (IL-2) and interferon-γ (INF-γ) were quantified by enzyme-linked immunosorbent assay (ELISA). The protein levels of transforming growth factor-beta 1 (TGF-β1), IL-33, ST2, and IL-1RAP in the nasal mucosa tissue were determined by Western blot. ResultsIL-33, ST2, and IL-1RAP had strong binding ability with the main active ingredients—wogonin, 7-methoxy-2-methylisoflavone, formononetin, naringenin, stigmasterol, and beta-sitosterol of QDYF, with the binding energy < -4.25 kcal⋅mol-1(1 cal≈4.184 J). The results of in vivo experiments showed that compared with the control group, the model group exhibited increased behavioral scores (P<0.05), aggravated pathological damage of nasal mucosa, increased collagen fiber deposition and CVF (P<0.05), elevated serum levels of IL-4, IL-5, and IL-13, up-regulated protein levels of TGF-β1, IL-33, ST2, and IL-1RAP in the nasal mucosa (P<0.05), down-regulated expression of E-cad, and declined serum levels of IL-2, IFN-γ, and IFN-γ/IL-4 ratio (P<0.05). Compared with the model group, the QDYF groups and loratadine group showed reduced behavioral scores (P<0.05), alleviated pathological damage of nasal mucosa, reduced collagen fiber deposition and CVF (P<0.05), and up-regulated E-cad expression (P<0.05). Compared with the model group, the QDYF-H group and the loratadine group showed raised levels of INF-γ and IFN-γ/IL-4 ratio (P<0.05), declined serum levels of IL-4, IL-5, and IL-13, and down-regulated protein levels of TGF-β1, IL-33, ST2, and IL-1RAP in the nasal mucosa (P<0.05). In addition, the QDYF-H group exhibited an elevated serum IL-2 level (P<0.05). The QDYF-M group showed down-regulated protein levels of TGF-β1, IL-33 and IL-1RAP in the nasal mucosa (P<0.05). The QDYF-L group demonstrated a down-regulated protein level of ST2 in the nasal mucosa (P<0.05). ConclusionQDYF may regulate the Th1/Th2 balance through the IL-33/ST2/IL-1RAP signaling pathway, thereby ameliorating nasal mucosal tissue remodeling and alleviating AR.
3.Effects of transcutaneous auricular vagus nerve stimulation on functional brain activity in patients with prolonged disorders of consciousness: A randomized controlled trial protocol using functional near-infrared spectroscopy and electroencephalography
Huan OUYANG ; Yifei WANG ; Ying HAN ; Jinling ZHANG ; Liang LI ; Chen XIN ; Jianghong HE ; Peijing RONG
Science of Traditional Chinese Medicine 2026;4(2):181-187
Background: Advances in intensive care have markedly improved survival after severe brain injury, leading to a growing population of patients with prolonged disorders of consciousness (pDOC). Current management of pDOC remains largely supportive, and evidence-based neuromodulatory interventions are limited; moreover, existing guidelines provide insufficiently explicit recommendations regarding mechanisms of action and objective biomarkers of treatment response. Transcutaneous auricular vagus nerve stimulation (taVNS) has emerged as a potential noninvasive intervention; however, its modulatory effects on brain function in pDOC are not yet well characterized, and the paucity of integrative mechanistic evidence has constrained its translation into routine clinical practice. Objectives: Within a multimodal assessment framework, this study aims to systematically elucidate the neurobiological mechanisms by which taVNS modulates brain function and autonomic activity in patients with pDOC, and to evaluate its clinical potential to enhance levels of consciousness. Methods: In this randomized controlled trial, 60 patients with vegetative state/minimally conscious state will be enrolled and randomly allocated to a taVNS group, a transcutaneous nonauricular vagus nerve stimulation group (sham), or a control group (n = 20 per group) for a 4-week intervention. The primary outcome will be changes in the Coma Recovery Scale-Revised scores from baseline to weeks 1, 2, and 4 of treatment. Secondary outcomes will include functional brain activity assessed by electroencephalography and functional near-infrared spectroscopy, as well as autonomic modulation indexed by heart rate variability. Functional prognosis will be evaluated using the Glasgow Outcome Scale-Extended at the end of treatment and at a 6-month follow-up. Safety will be assessed by continuous monitoring and documentation of adverse events throughout the study period. Results and discussion: By integrating electroencephalography–functional near-infrared spectroscopy with heart rate variability, this study will characterize the effects of taVNS on functional brain networks and consciousness recovery in pDOC across complementary behavioral, electrophysiological, hemodynamic, and autonomic domains, while interrogating potential sources of clinical and neurobiological heterogeneity. The findings are expected to provide a mechanistic and evidence-based foundation for the mechanism-driven clinical implementation of taVNS and the optimization of stimulation protocols in pDOC. Clinical trial registration: International Traditional Medicine Clinical Trial Registry, ITMCTR20250021041, https://itmctr.ccebtcm.org.cn.
4.Differences in deltamethrin resistance and kdr gene mutation in Culex tritaeniorhynchus population in and outside the Yellow Sea wetland
Xiao-er ZHANG ; Zhi-ming WU ; Ye TIAN ; Qian CUI ; Yu-qian JI ; Huan WANG ; Shu-juan YANG ; Yi-chao ZHAO ; Yu WANG ; Hua-yu YIN ; Yu DING ; Guo-jin YAN ; Min-sen ZHAO ; Shou-gang ZHANG ; Bing-dong SONG ; Hong-na CHEN ; Jian GAO ; Wei-fang YANG ; Yu-fu ZHANG ; Hui LIU ; Hong-liang CHU
Acta Parasitologica et Medica Entomologica Sinica 2026;33(2):101-107
Objective To gain insights into the biological characteristics of different populations of Culex tritaeniorhynchus within and around the Yellow Sea wetland from the perspective of the occurrence of resistance, we investigated the levels of resistance to deltamethrin and kdr gene mutation in the wetland and its peripheral areas. Methods Specimens were collected from Cx. tritaeniorhynchus populations at two monitoring sites in the Rare Bird National Nature Reserve and Tiaozi Ni Wetland Scenic Area, and also from two populations in Yancheng City and the Liuhe District of Nanjing, and the resistance of these mosquitoes to deltamethrin was determined using the CDC biotest bottle method. For each concentration of deltamethrin assessed, a random subset of exposed specimens was selected for amplification of the kdr gene fragment, followed by Sanger sequencing to identify and analyze resistance-associated mutations. Results The LC50 levels of deltamethrin among mosquitoes from the four populations in Luhe, Yancheng, the Rare Bird National Nature Reserve and the Tiaozi Ni Wetland Scenic Area were 2.048 5, 7.798 2, 3.473 3, and 17.695 5 mg/mL, respectively, with corresponding concentrations of deltamethrin ranging from 0.005 to 5.000,0.050 to 50.000,0.050 to 25.000 and 0.050 to 50.000 mg/mL, respectively. Furthermore, the ranges of the KT50 values were 11.76-107.43, 67.05-216.30,29.77-107.43 and 28.40-329.51 min; the 1-h knockdown rates were 34.58%-99.15%, 9.52%-43.80%, 55.09%-73.01%, and 10.09%-68.07%; and the 24-h mortality rates were 12.15%-67.52%,9.52%-79.56%,13.17%-82.21%, and 11.01%-78.99%, respectively. With respect to kdr gene mutation, we assayed a total of 63,70,59, and 57 mosquitoes for the four populations, for which we detected L1014F mutation frequencies of 14.29%, 35.00%, 20.34%, and 31.58%, respectively, with a majority of these mutations being heterozygous for resistance. In addition, five adult mosquitoes were identified has having synonymous mutations at site 1011[i. e. , AAT(asparagine)mutation to AAC(asparagine)]. Conclusions Our findings revealed the clear resistance of Cx. tritaeniorhynchus to deltamethrin in the Yancheng region of the Yellow Sea wetland, and the resistance phenotype and kdr frequency of Cx. tritaeniorhynchus in the wetland environment were comparable to those of Cx. tritaeniorhynchus in the wetland environment, thereby indicating that the resistance of different populations of Cx. tritaeniorhynchus was homogeneous under the pressure of different insecticide selection within and around the wetland. However, the underlying mechanisms need to be further studied.
5.Transcranial Focused Ultrasound Stimulation of the Primary Somatosensory Cortex Evokes Hand Tactile Perception: The Effect of Sonication Duration
Xu-Xu CHEN ; Huan-Jun XI ; Zhen LIANG ; Bo WANG ; Xu-Dong ZHAO
Progress in Biochemistry and Biophysics 2026;53(7):1942-1952
ObjectiveTranscranial focused ultrasound (tFUS) has emerged as a promising noninvasive neuromodulation technique capable of modulating neural activity with high spatial specificity. However, whether tFUS stimulation of the primary somatosensory cortex (S1) can reliably evoke conscious tactile perception without external peripheral sensory input remains unclear. Therefore, this study examined the feasibility of inducing hand-related tactile perception through targeted S1 stimulation and further investigated how sonication duration (SD), a key temporal parameter, influences the consistency of this perceptual response. The findings may provide empirical evidence for optimizing tFUS parameters in human somatosensory modulation. MethodsForty-eight healthy adults participated in the study and were assigned to two experiments. Experiment 1 included 24 participants and was designed to preliminarily examine whether S1-targeted tFUS could evoke hand-related tactile sensations. This experiment comprised two sub-experiments, Experiment 1a and Experiment 1b, with 12 participants in each. Specifically, Experiment 1a used a randomized active stimulation protocol targeting the bilateral S1 to assess the initial feasibility of inducing contralateral tactile perception, whereas Experiment 1b employed an alternating hemispheric design incorporating both active and sham stimulation to verify the specificity of the tFUS-induced sensations. Experiment 2 enrolled another 24 participants and used a real-sham dual-probe design to control for spatial tactile cues that might arise from probe-scalp contact. Five SD levels, including 200, 400, 600, 800, and 1 000 ms, were systematically tested to evaluate how stimulation duration influenced the behavioral response. The primary behavioral outcome was the perceptual consistency rate, quantified according to the accuracy of contralateral tactile localization. ResultsIn Experiment 1, 91.7% of participants reported reliable hand-related tactile sensations during active tFUS stimulation, including numbness, tingling, or similar sensory experiences. Contralateral localization accuracy under active stimulation was significantly higher than the0.50 chance level (P<0.05). In contrast, localization performance under sham stimulation did not differ from chance, suggesting that the observed tactile responses were mainly induced by active S1-targeted tFUS stimulation rather than nonspecific stimulation cues. In Experiment 2, perceptual consistency rates significantly exceeded the chance level under the 400 and 1 000 ms SD conditions(P<0.05), whereas no significant effect was observed at 200, 600, or 800 ms. Pairwise comparisons further showed that the 400 and 1 000 ms conditions produced significantly higher perceptual consistency rates than the 200 ms condition (P<0.05). ConclusiontFUS stimulation of S1 can elicit distinct hand-related tactile sensations without peripheral sensory input, demonstrating the feasibility of using targeted cortical ultrasound stimulation to induce conscious somatosensory perception. The reliability of this perceptual effect was modulated by sonication duration, indicating that temporal stimulation parameters play an important role in shaping both the occurrence and consistency of behavioral responses. Among the tested conditions, 400 ms appeared to provide a favorable temporal window for generating stable tactile perception, whereas excessively short stimulation may be insufficient to produce consistent responses. These findings highlight the sensitivity of somatosensory networks to ultrasonic modulation and provide useful parameter guidance for the application of tFUS in noninvasive sensory enhancement and cortical functional mapping.
6.Dual Targeting of TBK1 and JAK-STAT1 Pathways by (-)-epigallocatechin-3-gallate Suppresses Type I Interferon-driven Inflammation
Liang LI ; Qi-Huan SHENG ; Huan LIU ; Wen-Hao YANG ; Jia-Lin SHI ; Ying-Jie SUN ; Rui JING ; Wei-Hua MAI ; Zhi-Min LI ; Xiao-Li XIE
Progress in Biochemistry and Biophysics 2026;53(7):1969-1983
ObjectiveType I interferon (IFN-I) signaling is essential for antiviral innate immunity, yet its sustained or excessive activation contributes to the pathogenesis of several autoimmune diseases and interferonopathies, such as systemic lupus erythematosus and Aicardi-Goutières syndrome. Current strategies targeting this pathway, exemplified by JAK inhibitors, act mainly on downstream signal transduction and provide limited direct control over upstream IFN-I production, while also carrying the risk of broad immunosuppression. Phyllanthus emblica L. has long been used in traditional medicine for inflammatory disorders, but the bioactive constituent responsible for its regulation of IFN-I signaling and the underlying molecular mechanism have not been clearly defined. This study aimed to identify the active anti-inflammatory component of P. emblica and to characterize its mechanism of action on the IFN-I pathway in macrophages. MethodsActive components ofP. emblica and their candidate targets were screened by network pharmacology using the TCMSP and DrugBank databases (oral bioavailability≥30%, drug-likeness≥0.18) and intersected with inflammation-related genes retrieved from public databases. The predicted interaction between EGCG and IFN-I pathway proteins (TBK1, IRF3, STAT1) was evaluated by molecular docking, with BX795 and GSK8612 used as reference TBK1 inhibitors. Mechanistic experiments were performed in THP-1-derived macrophages and primary bone marrow-derived macrophages (BMDM). Upstream signaling was activated by transfection of the nucleic acid analogs poly(I∶C) and poly(dA∶dT) or by lipopolysaccharide (LPS) stimulation, whereas downstream signaling was activated by exogenous IFN-β. An siRNA-mediated TREX1 knockdown model was used to mimic endogenous nucleic acid-driven interferonopathy. Expression of IFN-β1 and interferon-stimulated genes (ISGs) was measured by RT-qPCR, protein phosphorylation by Western blot, and IFN-β secretion by ELISA. Cellular thermal shift assay (CETSA) and drug affinity responsive target stability (DARTS) were used to probe the interactionbetween EGCG and IRF3. ResultsNetwork pharmacology identified (-)-epigallocatechin-3-gallate (EGCG) as a candidate IFN-I-suppressive constituent of P. emblica, with predicted binding to TBK1, IRF3, and STAT1. Molecular docking yielded binding energies of -9.2, -7.2, and -8.2 kcal/mol for TBK1, IRF3, and STAT1, respectively, indicating an affinity for TBK1 comparable to that of the reference inhibitors BX795 (-5.7 kcal/mol) and GSK8612 (-6.4 kcal/mol). EGCG suppressed IFN-β1 and ISG mRNA expression under poly (I∶C), poly (dA∶dT), and LPS stimulation in both THP-1 macrophages and BMDM. At the protein level, EGCG reduced the phosphorylation of TBK1 and IRF3 without affecting the levels of the upstream sensors cGAS and RIG-I, and lowered IFN-β secretion in a concentration-dependent manner. CETSA and DARTS showed that EGCG did not enhance the thermal stability or protease resistance of IRF3, indicating that its effect on IRF3 is indirect. Following IFN-β stimulation, prolonged EGCG treatment reduced STAT1 phosphorylation in a time-dependent manner without an apparent change in IRF9, and partially attenuated ISG transcription; this effect was not monotonicly concentration-dependent, and CXCL10 showed the most consistent suppression. In TREX1-knockdown cells, the elevated mRNA levels of ISG15, ISG56, and CXCL10 were reduced by EGCG. ConclusionEGCG suppresses IFN-I responses by concurrently inhibiting TBK1-IRF3-dependent IFN‑β production and JAK-STAT1-mediated downstream transcription. These in vitro findings provide a mechanistic basis for the anti-inflammatory use of P. emblica in traditional medicine and identify EGCG as a candidate for further evaluation in interferon-driven autoimmune disease models.
7.Setup Error and Its Influencing Factors in Radiotherapy for Spinal Metastasis
Wenhua QIN ; Xin FENG ; Zengzhou WANG ; Shangnan CHU ; Hong WANG ; Shiyu WU ; Cheng CHEN ; Fukui HUAN ; Bin LIANG ; Tao ZHANG
Cancer Research on Prevention and Treatment 2025;52(5):400-404
Objective To investigate the setup error in patients with spinal bone metastasis who underwent radiotherapy under the guidance of kilovoltage cone-beam CT (KV-CBCT). Methods A total of 118 patients with spinal metastasis who underwent radiotherapy, including 17 cases of cervical spine, 62 cases of thoracic spine, and 39 cases of lumbar spine, were collected. KV-CBCT scans were performed using the linear accelerators from Elekta and Varian’s EDGE system. CBCT images were registered with reference CT images in the bone window mode. A total of 973 data were collected, and 3D linear errors were recorded. Results The patients with spinal bone metastasis were grouped by site, height, weight, and BMI. The P value of the patients grouped only by site was P<0.05, which was statistically significant. Conclusion When grouped by site in the 3D direction, the positioning effect of cervical spine is better than that of thoracic and lumbar spine. The positioning effect of the thoracic spine is better in the head and foot direction but worse in the left and right direction compared with that of the lumbar spine. Instead of extending or narrowing the margin according to the BMI of patients with spinal metastasis, the margin must be changed according to the site of spinal bone metastasis.
8.Value of color Doppler ultrasound combined with shear wave elastography in predicting the recurrence risk of breast cancer after operation
Huan WANG ; Jun WANG ; Qiuping WANG ; Jia LI ; Xinxing LIANG
Chinese Journal of Endocrine Surgery 2025;19(5):666-670
Objective:To assess the effectiveness of combining color Doppler ultrasound (CDU) with shear wave elastography (SWE) in forecasting the likelihood of breast cancer (BC) recurrence.Methods:From Jan. 2022 to Jan. 2024, we gathered data on 92 BC patients admitted to Shanxi Maternal and Child Health Hospital and Shanxi Cancer Hospital, focusing on their lesion characteristics. Each patient underwent CDU and SWE examinations pre-surgery and was monitored for a year. Based on BC recurrence, patients were categorized into recurrence and non-recurrence groups. We compared CDU imaging and hemodynamic features of BC between these groups and evaluated SWE elastic modulus values. To assess the agreement between CDU, SWE, and their combined use in predicting BC recurrence and pathological diagnosis, we employed the Kappa test. Additionally, we plotted ROC curves to analyze the predictive power of CDU, SWE, and their combination in assessing BC recurrence risk. Results:Among the 92 BC patients studied, 38 experienced recurrence, while 54 did not. CDU examination revealed that the non-recurrence group exhibited significantly larger tumor maximum diameter, higher peak systolic velocity (PSV), a higher proportion of aspect ratio ≥ 1, irregular margins, calcification, and increased vascular abundance, compared to the recurrence group ( t/ χ2=17.188, 18.491, 6.099, 15.374, 14.526, 19.318, P<0.05). Additionally, the vascular resistance index (RI) was lower in the non-recurrence group ( t=-26.429, P<0.05). SWE results indicated that the recurrence group had higher average (E mean), maximum (E max), and minimum (E min) elastic moduli compared to the non-recurrence group ( t=14.39, 12.34, 8.29, P<0.05). CDU and SWE predictions showed substantial agreement with pathological results, with Kappa values of 0.66 and 0.69, respectively ( P<0.05). The combination of CDU and SWE predictions demonstrated excellent concordance with pathological outcomes ( Kappa=0.91, P<0.05). In terms of predicting BC recurrence risk, CDU and SWE had accuracies of 83.70% and 84.21%, respectively. The ROC curve analysis showed AUC values of 0.830 for CDU, 0.847 for SWE, and 0.955 for their combination. Sensitivity was 0.870 for CDU, 0.852 for SWE, and 0.963 for the combination. Specificity was 0.789 for CDU, 0.842 for SWE, and 0.947 for the combination. Positive predictive values were 78.95% for CDU, 84.21% for SWE, and 94.74% for the combination, while negative predictive values were 87.04% for CDU, 85.19% for SWE, and 96.30% for the combination. The AUC for CDU in predicting post-operative BC recurrence risk was not significantly different from SWE ( χ2=0.04, P>0.05), but the combined prediction AUC was significantly higher than individual predictions ( χ2=8.00, 7.04, P<0.05) . Conclusion:The predictive value of CDU and SWE combined examination for the recurrence risk of BC is better than that of single examination, and it is suggested that the combined examination method should be popularized in clinic.
9.4-week high-intensity interval training regulates the mitochondrial unfolded protein response in skeletal muscle to improve depressive-like behavior in chronic unpredictable mild stress model rats
Jiaren LIANG ; Yumei HAN ; Chunhui BAO ; Ziwei ZHANG ; Junsheng TIAN ; Yonghong YANG ; Huan XIANG
Chinese Journal of Comparative Medicine 2025;35(3):1-14
Objective To investigate the mechanism by which 4-week high-intensity interval training(HIIT)regulates the mitochondrial unfolded protein response(UPRmt)in skeletal muscle and improves mitochondrial function in a rat model of chronic unpredictable mild stress(CUMS).Methods Male SPF-grade SD rats(6~8 weeks old)were divided randomly into control(C),model(M),HIIT+control(HC),and HIIT+model(HM)groups.Rats in the M and HM groups were subjected to CUMS for 8 weeks to establish a depression model,while rats in the HC and HM groups received HIIT for 5 d a week for 4 weeks.The exercise regimen consisted of 3 min high-speed(85%~90%Smax)combined with 1 min low-speed(50%~55%Smax)uninterrupted repetitive training(Smax is maximum training speed).Behavioral changes were evaluated at weeks 4 and 8.Tissue samples were taken 24 h after the last behavioral test and skeletal muscle mitochondria were examined by transmission electron microscopy.The ATP and reactive oxygen species(ROS)contents were measured by enzyme-linked immunosorbent assays and protein expression levels of activating transcription factor(ATF)4,ATF5,C/EBP homologous protein(CHOP),and heat shock protein 60(HSP60)were detected by Western blot.Results(1)The body mass,number of crossing grids,number of upright positions,sugar-water preference rate,and ATP content were significantly decreased in group M compared with group C(P<0.01),while the number of damaged mitochondria,ROS content,ATF4,ATF5,CHOP,and HSP60 protein expression were significantly increased(P<0.01).(2)After 4-weeks of HIIT intervention,the ATP content and ATF4 and ATF5 protein expression levels were significantly increased in the HC group compared with C group(P<0.05,P<0.01).The number of crossing grids,number of upright positions,sugar-water preference rate,ATP content,and ATF4 protein expression were significantly increased in the HM group compared with M group(P<0.01),while the number of damaged mitochondria,ROS content,and ATF5,CHOP,and HSP60 protein expression levels were significantly decreased(P<0.01).(3)After 4 weeks of HIIT intervention,the number of crossing grids in CUMS rats was significantly positively correlated with ATF4 protein expression,and ROS content was correlated with CHOP protein expression,number of damaged mitochondria,and ATF5 protein expression(|r|>0.75,P<0.01;|r|>0.75,P<0.05).Upright frequency was significantly negatively correlated with ATF5 and HSP60 protein expression,the number of crossing grids,the sugar-water preference rate,and the expression of CHOP and HSP60 proteins(|r|<0.75,P<0.05).Conclusions 4-week HIIT intervention can improve mitochondrial dysfunction and alleviate depressive-like behavior in CUMS rats by regulating skeletal muscle UPRmt.
10.Analysis of gene detection results of next-generation sequencing of liquid based cytological specimens of lung adenocarcinoma cavity effusion and evaluation of clinical efficacy
Shuo LIANG ; Yuan WANG ; Zihan SUN ; Jiameng ZHANG ; Xiaoyue XIAO ; Cong WANG ; Yue SUN ; Xinxiang CHANG ; Linlin ZHAO ; Huan ZHAO ; Huiqin GUO ; Zhihui ZHANG
Chinese Journal of Oncology 2025;47(9):905-912
Objective:To analyze the results of next generation sequencing (NGS) gene testing in liquid-based cytological specimens of lung adenocarcinoma cavity and evaluate the clinical efficacy of epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) treatment.Methods:Liquid based cytological specimens of 222 cases of lung adenocarcinoma with cavity effusion and 201 cases of metastatic lymph node biopsy were collected. Specimens were obtained from the Cytology Laboratory of the Cancer Hospital of the Chinese Academy of Medical Sciences. The collection period was from January 2018 to December 2022. The results of NGS gene detection were compared. The clinical efficacy of 91 patients treated with EGFR-TKI was evaluated, and the survival curve was analyzed by Kaplan-Meier and other statistical methods.Results:The mutation rates of cancer-related genes detected by NGS were 82.0% (182/222) vs 79.1% (159/201), ( P=0.455) in liquid-based cytological specimens and histological specimens of metastatic lymph node biopsy, respectively. However, the mutation rate of EGFR T790M was significantly higher in cavity effusion than in lymph node biopsy specimens [12.2%(27/222)>3.5%(7/201), P=0.001]. The results of gene mutation were identical in 10 of the 13 cases with cavity effusion and metastatic lymph node biopsy, and the agreement rate of EGFR was 84.6%(11/13). In 3 inconsistent cases, EGFR mutations were detected in 2 cavity effusion cases that were not detected by lymph node biopsy. Results of genetic analysis of fluid-based cytological samples of 91 patients with cavity effusion were evaluated after drug treatment with EGFR-TKI. The mean progression-free survival (PFS) of the patients was 11.4 months (95% CI: 9.9-12.9). The mean PFS of patients harboring EGFR mutation was 12.3 months (95% CI: 10.8-13.9), and the mean PFS of EGFR wild type was 4.1 months (95% CI: 2.1-6.2). Conclusions:The results of NGS gene detection in liquid-based cytological specimens of lung adenocarcinoma patients with cavity effusion show that the PFS time is similar to that of histological specimens after clinical treatment with EGFR-TKI, which proves the reliability of NGS gene detection results in liquid cytological specimens. NGS gene testing appears higher sensitivity in cavity liquid-based samples than in metastatic lymph node samples.


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