Objective To investigate the role of mitochondrial transcription factor A (TFAM) in platinum-resistant ovarian cancer cells and its effects on metabolic reprogramming and sensitivity to platinum-based drugs Methods The mitochondrial function and metabolic characteristics of platinum-resistant ovarian cancer cells were analyzed. A TFAM-overexpressing cell model was established to assess its effects on platinum sensitivity, mitochondrial function, and aerobic glycolysis; and glycolytic enzyme and drug-resistant protein expression were analyzed. Results Platinum-resistant ovarian cancer cells exhibited considerable mitochondrial dysfunction (reduced oxygen consumption rate) and enhanced aerobic glycolysis (increased extracellular acidification rate, glucose uptake, and lactate production). TFAM was downregulated in resistant cells. Meanwhile, TFAM overexpression significantly enhanced platinum sensitivity (P<0.01), restored mitochondrial function, and inhibited aerobic glycolysis. The expression levels of glycolytic enzymes and drug-resistant proteins were also downregulated (P<0.05). Conclusion TFAM downregulation is associated with suppressed oxidative phosphorylation and enhanced aerobic glycolysis in platinum-resistant ovarian cancer cells. TFAM overexpression can restore cellular dependence on oxidative phosphorylation and increase platinum sensitivity, suggesting that TFAM is a potential therapeutic target for reversing platinum resistance.

Urticarial vasculitis is a skin disease with urticaria-like lesions and a histopathological pattern of leukocytoclastic vasculitis. It is considered a "hidden rash" in traditional Chinese medicine. Xuanfu is the portal that regulates qi, blood, fluid, and the ascending, descending, exiting, and entering of nutrition qi and defensive qi. Collaterals are the pathways for the circulation of qi and blood. The two accompany each other, connecting zang-fu organs, reaching the surfaces of the skin, hair, and external body, circulating qi and fluid, and moistening and protecting the skin. Based on the theory of Xuanfu-collateral, this study aimed to clarify the etiology, pathogenesis, and treatment method of urticarial vasculitis. External assault by wind and Xuanfu blockage are believed to be the initiating factors of this disease. The malnutrition of Xuanfu and collaterals and accumulated dampness-heat are important links in the occurrence and development of urticarial vasculitis. It spreads from Xuanfu to the collaterals, and blockage of the collaterals is the immanent trend of this disease. Clinically, by closely adhering to the core pathogenesis of blockage of Xuanfu-collateral, treatment method such as using wind medicinals to open Xuanfu with pungent and dispersing properties, using the method of supplement deficiency and removing the blockage, and using medicinals to promote blood circulation and remove blood stasis to unblock the blocked collaterals. The herbs are flexibly added or subtracted to unblock Xuanfu and collaterals, harmonize qi and blood, thus all symptoms can be relieved. We hope that this study will provide new ideas for the treatment of urticarial vasculitis with traditional Chinese medicine.

BACKGROUND: Asthma is a common chronic inflammatory airway disease and intermittent hypoxia is increasingly recognized as a factor that may impact disease progression. The present study investigated whether intermittent hypoxia (IH) could aggravate asthma by promoting hypoxia-inducible factor-1α (HIF-1α)/nucleotide-binding oligomerization domain (NOD)-like receptor pyrin domain-containing protein 3 (NLRP3)/interleukin (IL)-1β-dependent pyroptosis and the inflammatory response and further elucidated the underlying molecular mechanisms involved. METHODS: A total of 49 patients diagnosed with severe bronchial asthma and diagnosed by polysomnography were enrolled at Tongji Hospital, Tongji Medical College of Huazhong University of Science and Technology, between January 2022 and December 2022, and their general data and induced sputum were collected. BEAS-2B cells were treated with IL-13 and subjected to IH. An ovalbumin (OVA)-treated mouse model was also used to assess the effects of chronic intermittent hypoxia (CIH) on asthma. Pyroptosis, the inflammatory response, and related signalling pathways were assessed in vivo and in vitro . RESULTS: In this study, as the apnoea and hypopnea index (AHI) increased, the proportion of patients with uncontrolled asthma increased. The proportions of neutrophils and the levels of IL-6, IL-8, HIF-1α and NLRP3 in induced sputum were related to the AHI. NLRP3-mediated pyroptosis, which could be mediated by the HIF-1α signalling pathway, was activated in IL-13 plus IH-treated BEAS-2B cells and in the lungs of OVA/CIH mice. HIF-1α downregulation significantly reduced lung pyroptosis and ameliorated neutrophil inflammation by modulating the NLRP3/IL-1β pathway both in vitro and in vivo . Similarly, pretreatment with LW6, an inhibitor of HIF-1α, effectively blocked the generation of inflammatory cytokines in neutrophils. In addition, administration of the NLRP3 activator nigericin obviously increased lung neutrophil inflammation. CONCLUSIONS Obstructive sleep apnoea-hypopnea syndrome (OSAHS) is a risk factor for asthma exacerbation. IH aggravates neutrophil inflammation in asthma via NLRP3/IL-1β-dependent pyroptosis mediated by the HIF-1α signalling pathway, which should be considered a potential therapeutic target for the treatment of asthma with OSAHS.
NLR Family, Pyrin Domain-Containing 3 Protein/metabolism* ; Humans ; Asthma/metabolism* ; Animals ; Pyroptosis/physiology* ; Hypoxia-Inducible Factor 1, alpha Subunit/metabolism* ; Mice ; Signal Transduction/physiology* ; Male ; Hypoxia/metabolism* ; Female ; Interleukin-1beta/metabolism* ; Adult ; Inflammation/metabolism* ; Middle Aged ; Mice, Inbred C57BL

Objective:This study aims to explore the predictive value of T2-weighted imaging (T2WI), apparent diffusion coefficient (ADC), and early-delayed phases enhanced magnetic resonance imaging (DCE-MRI) radiomics prediction model in determining human epidermal growth factor receptor 2 status in breast cancer.Methods:A retrospective study was conducted, involving 187 patients with confirmed breast cancer by postsurgical pathology at Zhenjiang First People's Hospital during January 2021 and May 2023. Immunohistochemistry or fluorescence in situ hybridization was used to determine the HER-2 status of these patients, with 48 cases classified as HER-2 positive and 139 cases as HER-2 negative. The training set was used to construct the prediction models and the validation set was used to verify the prediction models. Layers of T2WI, ADC, and early-delayed phase DCE-MRI images were used to delineate the volumeof interest and 960 radiomic features were extracted from each case using Pyradiomic. After screening and dimensionality reduction by intraclass correlation coefficient, Pearson correlation analysis, least absolute shrinkage, and selection operator, the radiomics labels were established. Logistic regression analysis was used to construct the T2WI radiomics model, ADC radiomics model, DCE-2 radiomics model, DCE-6 radiomics model, and the joint sequence radiomics model to predict the HER-2 expression status of breast cancer, respectively. Based on the clinical, pathological, and MRI image characteristics of patients, univariate and multivariate logistic regression analysis wasused to construct a clinicopathological MRI feature model. The radscore of every patient and the clinicopathological MRI features which were statistically significant after screening were used to construct a nomogram model. The receiver operating characteristic (ROC) curve was used to evaluate the predictive performance of each model and the decision curve analysis wasused to evaluate the clinical usefulness.Results:The T2WI, ADC, DCE-2, DCE-6, and joint sequence radiomics models, the clinicopathological MRI feature model, and the nomogram model were successfully constructed to predict the expression status of HER-2 in breast cancer. ROC analysis showed that in the training set and validation set, the areas under the curve (AUC) of the T2WI radiomics model were 0.797 and 0.760, of the ADC radiomics model were 0.776 and 0.634, of the DCE-2 radiomics model were 0.804 and 0.759, of the DCE-6 radiomics model were 0.869 and 0.798, of the combined sequence radiomics model were 0.908 and 0.847, of the clinicopathological MRI feature model were 0.703 and 0.693, and of the nomogram model were 0.938 and 0.859, respectively. In the training set, the combined sequence radiomics model outperformed the clinicopathological features model ( P＜0.001). In the training and validation sets, the nomogram outperformed the clinicopathological features model ( P＜0.05). In addition, the diagnostic performance of the nomogram was better than that of the four single-modality radiomics models in the training cohort ( P＜0.05) and was better than that of DCE-2 and ADC models in the validation cohort ( P＜0.05). Decision curve analysis indicated that the value of individualized prediction models was higher than clinical and pathological prediction models in clinical practice. The calibration curve showed that the multimodal radiomics model had a high consistency with the actual results in predicting HER-2 expression. Conclusions:T2WI, ADC and early-delayed phase DCE-MRI imaging histology models for HER-2 expression status in breast cancer are expected to provide a non-invasive virtual pathological basis for decision-making on preoperative neoadjuvant regimens in breast cancer.

Objective:This study aims to explore the predictive value of T2-weighted imaging (T2WI), apparent diffusion coefficient (ADC), and early-delayed phases enhanced magnetic resonance imaging (DCE-MRI) radiomics prediction model in determining human epidermal growth factor receptor 2 status in breast cancer.Methods:A retrospective study was conducted, involving 187 patients with confirmed breast cancer by postsurgical pathology at Zhenjiang First People's Hospital during January 2021 and May 2023. Immunohistochemistry or fluorescence in situ hybridization was used to determine the HER-2 status of these patients, with 48 cases classified as HER-2 positive and 139 cases as HER-2 negative. The training set was used to construct the prediction models and the validation set was used to verify the prediction models. Layers of T2WI, ADC, and early-delayed phase DCE-MRI images were used to delineate the volumeof interest and 960 radiomic features were extracted from each case using Pyradiomic. After screening and dimensionality reduction by intraclass correlation coefficient, Pearson correlation analysis, least absolute shrinkage, and selection operator, the radiomics labels were established. Logistic regression analysis was used to construct the T2WI radiomics model, ADC radiomics model, DCE-2 radiomics model, DCE-6 radiomics model, and the joint sequence radiomics model to predict the HER-2 expression status of breast cancer, respectively. Based on the clinical, pathological, and MRI image characteristics of patients, univariate and multivariate logistic regression analysis wasused to construct a clinicopathological MRI feature model. The radscore of every patient and the clinicopathological MRI features which were statistically significant after screening were used to construct a nomogram model. The receiver operating characteristic (ROC) curve was used to evaluate the predictive performance of each model and the decision curve analysis wasused to evaluate the clinical usefulness.Results:The T2WI, ADC, DCE-2, DCE-6, and joint sequence radiomics models, the clinicopathological MRI feature model, and the nomogram model were successfully constructed to predict the expression status of HER-2 in breast cancer. ROC analysis showed that in the training set and validation set, the areas under the curve (AUC) of the T2WI radiomics model were 0.797 and 0.760, of the ADC radiomics model were 0.776 and 0.634, of the DCE-2 radiomics model were 0.804 and 0.759, of the DCE-6 radiomics model were 0.869 and 0.798, of the combined sequence radiomics model were 0.908 and 0.847, of the clinicopathological MRI feature model were 0.703 and 0.693, and of the nomogram model were 0.938 and 0.859, respectively. In the training set, the combined sequence radiomics model outperformed the clinicopathological features model ( P＜0.001). In the training and validation sets, the nomogram outperformed the clinicopathological features model ( P＜0.05). In addition, the diagnostic performance of the nomogram was better than that of the four single-modality radiomics models in the training cohort ( P＜0.05) and was better than that of DCE-2 and ADC models in the validation cohort ( P＜0.05). Decision curve analysis indicated that the value of individualized prediction models was higher than clinical and pathological prediction models in clinical practice. The calibration curve showed that the multimodal radiomics model had a high consistency with the actual results in predicting HER-2 expression. Conclusions:T2WI, ADC and early-delayed phase DCE-MRI imaging histology models for HER-2 expression status in breast cancer are expected to provide a non-invasive virtual pathological basis for decision-making on preoperative neoadjuvant regimens in breast cancer.

Objective To compare the sedative effect and safety of remimazolam and midazolam in synchronous electrical cardioversion in patients with atrial fibrillation.Methods Thirty-two patients with at-rial fibrillation receiving synchronous electrical cardioversion from January 2021 to December 2022 were en-rolled,22 males and 10 females,aged 18-80 years,BMI 20-30 kg/m2,ASA physical status Ⅱ or Ⅲ.The patients were randomly divided into two groups using random number table method:remimazolam group and midazolam group,16 patients in each group.The remimazolam group was sedated with 0.2 mg/kg of intra-venous remimazolam,and the midazolam group was sedated with 0.025 mg/kg of midazolam intravenously,and the drug injection time in both groups was 1 min.The anesthesia onset time,awakening time,and ori-entation recovery time were recorded.SBP,DBP,and SpO2 were recorded before anesthesia induction(T,),when the eyelash reflex was absent(T2),after the completion of electrical cardioversion(T3),and at the time of awakening(T4).Neurobehavioral cognitive state examination(NCSE)was performed 5 mi-nutes after the patients were awake,including language ability,structural ability,memory,calculation abil-ity and reasoning ability,and the pass rate of each ability test was calculated.The occurrence of adverse re-actions during surgery(body movement,apnea)and within 12 hours after surgery(nausea,vomiting,and chest pain)was recorded.Results Compared with the midazolam group,the anesthesia onset time,awak-ening time,and orientation recovery time in the remimazolam group were significantly shortened(P＜0.05).There was no significant difference in SBP,DBP,and Sp02 between the two groups at different time points.Compared with the midazolam group,the pass rate of the reasoning ability test was higher in the remimazolam group 5 minutes after awakening(P＜0.05).There was no significant difference in the inci-dence of adverse reactions between the two groups.Conclusion Compared with midazolam,remimazolam has faster onset of sedation,faster awakening,faster recovery of orientation in synchronous electrical cardio-version of atrial fibrillation,and faster recovery of reasoning ability in NCSE after synchronous electrical car-dioversion.

Objective:To study the epidemiological and clinical characteristics of brucellosis in Xinjiang Uygur Autonomous Region.Methods:A retrospective analysis method was used to collect medical records of 581 patients with brucellosis who visited the Xinjiang Uygur Autonomous Regional People's Hospital from January 2009 to December 2019. Demographic and epidemiological characteristics, clinical symptoms and signs, and laboratory test results of the patients were analyzed.Results:Among 581 patients with brucellosis, the male to female ratio was 2.8 ∶ 1.0 (428 ∶ 153). The age was (44.41 ± 16.25) years old, ranging from 1 - 83 years old, and mainly concentrated in 35 - 60 years old, accounting for 70.91% (412/581). The ethnic distribution was dominated by Uyghur, accounting for 50.60% (294/581). The occupational distribution was mainly farmers, accounting for 43.20% (251/581). A total of 186 patients had a clear history of contact with cattle and sheep, accounting for 32.01% (186/581). The clinical stage was dominated by patients in the acute stage, accounting for 55.25% (321/581). There were 48 cases of complications, accounting for 8.26%(48/581). The main clinical symptom of brucellosis patients was pain and fever, accounting for 73.67% (428/581) and 66.61% (387/581), respectively. Laboratory tests were dominated by increased blood sedimentation and C-reactive protein, accounting for 29.09% (169/581) and 23.06% (134/581), respectively. The positive rate of Brucella culture was low, accounting for 4.48% (26/581). Conclusions:The majority of brucellosis patients in Xinjiang Uygur Autonomous Region are young and middle-aged males, with the main occupation being farmers. The clinical symptoms are mostly pain and fever. The positive rate of Brucella culture in patients is relatively low. It is recommended to combine epidemiological and clinical features for diagnosis to reduce missed diagnosis and misdiagnosis, and detect and treat it early.

Objective To investigate the effects of terahertz(THz)radiation on mouse testicular tissue and its potential molecular mechanisms.Methods A total of 125 male C57BL/6J mice(6～8 weeks old)were randomly divided into control group and low-,medium-and high-radiation power groups.The mice of the latter 3 groups were exposed to THz radiation at a frequency of 2.5 T,with an average power density of 38,115,or 318 mW/cm2,for 5 or 10 min.The detection time was immediately or 24 h after exposure.HE staining was used to observe pathological damage.ELISA was employed to detect the expression of inflammatory factors in testicular tissue.RNA-seq was utilized to detect the global changes of gene expression.The differentially expressed genes(DEGs)were screened and bioinformatics was used to cluster them.The screened genes were further analyzed with RT-qPCR to determine the time-dependent and dose-dependent relationships of the expression with THz exposure.Finally,sperm quality was evaluated morphologically using a microscope.Results Three doses of THz radiation exposure did not cause significant pathological damages to mouse testicular tissue.TNF-α expression was increased immediately after exposure at average power density of 115 mW/cm2(P＜0.01),and the expression of IL-1β and TNF-α were both increased when the dose reached 318 mW/cm2(P＜0.01).However,all the 3 factors returned to normal levels in 24 h after exposure.RNA-seq results showed that THz radiation exposure caused abnormal expression of 56 genes.Cluster analysis indicated that these DEGs were mainly enriched in immune and inflammatory responses,enzyme activity,sperm development and capacitation functions.Then for 5 selected key genes,Crisp1,Adam7,Ltf,Rnase9,and Bsph1,the expression of Crisp1 and Rnase9 was decreased immediately after exposure to 115 mW/cm2 THz radiation,the dose of 318 mW/cm2 resulted in obvious changes in the expression of the 5 genes(P＜0.05),and their expression returned to normal levels in 24 h after exposure.Morphological observation displayed that exposure to all the 3 doses of THz had no influence on sperm quality.Conclusion THz radiation exposure causes temporary inflammatory response in testicular tissue and abnormal expression of sperm functions-related genes.However,these changes return to normal 24 h after exposure,and additionally,do not impair sperm quality.

Objective To evaluate the clinical value of neutrophil CD64(nCD64)index as a novel biomark-er in the differential diagnosis of acute and chronic brucellosis.Methods A total of 38 patients with acute bru-cellosis and 48 patients with chronic brucellosis diagnosed in the People's Hospital of Xinjiang Uygur Autono-mous Region from February 2021 to July 2023 were included.Peripheral blood of the patients was collected and nCD64 index was detected by flow cytometry,and the correlation between nCD64 index and disease severi-ty was analyzed.Receiver operating characteristic(ROC)curve was used to analyze the sensitivity and the specificity of nCD64 index in differentially diagnosing acute and chronic brucellosis.Meanwhile,Rose-Bengal Plate Test(RBPT)and Standard Tube Agglutination Test(SAT)were used as controls to evaluate the clini-cal diagnostic value of the three.Results The nCD64 index of acute brucellosis patients was higher than that of chronic brucellosis patients(U=216.00,P<0.001),and the index was positively correlated with the sever-ity of the disease(r=0.670,P<0.001).The ROC curve analysis results showed that the area under the curve of nCD64 index in the differential diagnosis of acute and chronic brucellosis was 0.882(95%CI:0.811-0.952,P<0.001),the cut-off value was 2.81,and sensitivity,specificity,positive predictive value,negative predictive value and accuracy were 83.3%,81.6%,80.4%,81.9%and 82.6%,respectively.The efficacy of nCD64 index in differential diagnosis of nCD64 index was significantly better than those of the qualitative tests of RBPT and SAT.Conclusion nCD64 index has favourable sensitivity and specificity in the differential diag-nosis of acute and chronic brucellosis,and tends to reflect the severity of the disease.It has clinical value in the differential diagnosis of acute brucellosis and chronic brucellosis,and plays an important role in the early diag-nosis and treatment effect monitoring of brucellosis.

Objective To investigate the characteristics of changes in interleukin(IL)-33 and regulatory T(Treg)cells in brucellosis,to verify the regulatory effect of IL-33 on Treg cells,so as to clarify the immune mechanism of IL-33 on Treg cells in brucellosis.Methods The peripheral blood of 39 patients with brucellosis treated in the People's Hospital of Xinjiang Uygur Autonomous Region from January to December 2021(the brucellosis group)and 42 healthy controls(the healthy control group)who underwent physical examination during the same period were collected.The serum IL-33 level was detected by AimPlex kit,and the proportion of Treg cells was detected by flow cytometry.Peripheral blood mononuclear cell(PBMC)was extracted and cultured in vitro to observe the proportion and mRNA expression levels of forkhead box protein P3(Foxp3)after stimulation and blocking of IL-33.Results Compared with the healthy control group,the level of IL-33 and the proportion of Treg cells in brucellosis group were significantly increased,with statistical significance(P＜0.05).In vitro tests showed that the Foxp3 proportion and mRNA expression level of PBMC in the two groups were significantly increased after IL-33 stimulation,and significantly decreased after IL-33 blocking,with statistical significance(P＜0.001).Conclusion IL-33 and Treg cells increased significantly in brucellosis patients,and IL-33 promoted the immune function of Treg cells.Blocking IL-33 is expected to be a potential target for immunotherapy of brucellosis.