ObjectiveTo investigate the effects of Linggui Zhugantang on mitochondrial fission and fusion and silencing information regulator 3（Sirt3）/adenosine monophosphate dependent protein kinase （AMPK） signaling pathway in chronic heart failure （CHF） rats after myocardial infarction （MI）. MethodSD rats randomly divide into sham operation group （normal saline ，thread only without ligature）， model group （normal saline， ligation of the left anterior descending coronary artery proximal to the heart）， Linggui Zhugantang group （4.8 g·kg^-1） and Captopril group （0.002 57 g·kg^-1）， with 10 rats in each group. Administere drug continuously for 28 days. Echocardiography detected cardiac function parameters. Hematoxylin eosin （HE） staining observed the pathological changes of the heart. Immunofluorescence detected the levels of reactive oxygen species （ROS）. JC-1 detect mitochondrial membrane potential. Colorimetry measure adenosine triphosphate （ATP）， superoxide dismutase （SOD）， malondialdehyde （MDA）， mitochondrial respiratory chain complex activity （Ⅰ-Ⅳ）. TdT-mediated dUTP nick end labeling （TUNEL） staining detected the apoptosis rate of myocardial tissue. Western blot detected protein expression levels of Sirt3， phosphorylated AMPK （p-AMPK）， phosphorylated dynamic-related protein 1（p-Drp1）， mitochondrial fission protein 1（Fis1）， mitochondrial fission factor （MFF）， optic atrophy protein 1（OPA1）. ResultCompared to the sham group， the left ventricular end diastolic diameter （LVIDd） and left ventricular end systolic diameter （LVIDs） were significantly increased in model group （P<0.01）， while the left ventricular short axis shortening rate （LVFS） and left ventricular ejection fraction （LVEF） were significantly decreased （P<0.01）. There were inflammatory cell infiltration and obvious pathological injury in myocardial tissue. ROS， MDA levels and myocardial cell apoptosis rate were significantly increased （P<0.01）， SOD level， ATP content， and membrane potential were significantly decreased （P<0.01）. The activity of mitochondrial respiratory chain complexes （Ⅰ-Ⅳ） was significantly decreased （P<0.01）. Levels of p-Drp1， Fis1， MFF proteins were significantly up-regulated （P<0.01）， while Sirt3， p-AMPK， OPA1 proteins level were significantly down-regulated （P<0.01）. Compared with model group， LVIDd and LVIDs were significantly decreased （P<0.01）， LVEF and LVFS were significantly increased （P<0.01）. Inflammatory cell infiltration and pathological damage of myocardial tissue were significantly relieved. ROS， MDA levels and myocardial cell apoptosis rate were significantly decreased in Linggui Zhugantang group and Captopril group （P<0.01）， SOD level， ATP content， and membrane potential significantly increased （P<0.01）. The activity of mitochondrial respiratory chain complexes （Ⅰ-Ⅳ） increased significantly （P<0.01），and p-Drp1， Fis1， MFF protein levels were significantly down-regulated （P<0.01）， Sirt3， p-AMPK， OPA1 protein were significantly up-regulated （P<0.01）. ConclusionLinggui Zhugantang can alleviate oxidative stress and apoptosis damage of myocardial cells， maintain mitochondrial function stability， and its effect may be related to mitochondrial mitosis fusion and Sirt3/AMPK signaling pathway.

AIM: To evaluate the effect of ab-externo circumferential suture trabeculotomy(CST)on the 24 h pattern of intraocular pressure(IOP)in primary open angle glaucoma(POAG).METHODS: This retrospective study included 18 POAG patients who had poor control of IOP from March 2021 to May 2022. The ab-externo CST was performed, and IOP was tested preoperatively and 1 a postoperatively(9:00 a.m., 12:00 a.m., 3:00 p.m., 6:00 p.m., 9:00 p.m., 12:00 p.m., 3 a.m., and 6:00 a.m.). The mean, peak, trough, and range of IOP, as well as the average diurnal-nocturnal IOP change were calculated and compared.RESULTS: The 24 h IOP curves exhibited a decreasing trend during the diurnal period and an increasing trend during the nocturnal period, reaching a trough in the afternoon and peaking at night; the time of trough and peak IOP occurred several hours earlier compared to preoperative eyes. Postoperatively, the mean, peak, and trough IOP values were significantly lower compared to preoperative levels. The range of fluctuation showed no significant difference, while the average diurnal-nocturnal IOP change increased significantly.CONCLUSION: CST could reduce IOP of patients with POAG, but could not change the range of IOP fluctuation. However, an increase in the average diurnal-nocturnal IOP change was observed, indicating that CST might not necessarily reduce diurnal-nocturnal IOP fluctuations.

Tyrosine kinase inhibitors (TKIs) have revolutionized the treatment landscape for chronic myeloid leukemia (CML). However, TKI resistance poses a significant challenge, leading to treatment failure and disease progression. Resistance mechanisms include both BCR::ABL1-dependent and BCR::ABL1-independent pathways. The mechanisms underlying BCR::ABL1 independence remain incompletely understood, with CML cells potentially activating alternative signaling pathways, including the AKT/mTOR and JAK2/STAT5 pathways, to compensate for the loss of BCR::ABL1 kinase activity. This study explored tumoral VISTA (encoded by VSIR) as a contributing factor to TKI resistance in CML patients and identified elevated tumoral VISTA levels as a marker of resistance and poor survival. Through in vitro and in vivo analyses, we demonstrated that VSIR knockdown and the application of NSC-622608, a novel VISTA inhibitor, significantly impeded CML cell proliferation and induced apoptosis by attenuating the AKT/ mTOR and JAK2/STAT5 pathways, which are crucial for CML cell survival independent of BCR::ABL1 kinase activity. Moreover, VSIR overexpression promoted TKI resistance in CML cells. Importantly, the synergistic effect of NSC-622608 with TKIs offers a potent therapeutic avenue against both imatinib-sensitive and imatinib-resistant CML cells, including those harboring the challenging T315I mutation. Our findings highlight the role of tumoral VISTA in mediating TKI resistance in CML, suggesting that inhibition of VISTA, particularly in combination with TKIs, is an innovative approach to enhancing treatment outcomes in CML patients, irrespective of BCR::ABL1 mutation status. This study not only identified a new pathway contributing to TKI resistance but also revealed the possibility of targeting tumoral VISTA as a means of overcoming this significant clinical challenge.

We conducted a prospective study to assess the non-inferiority of adjuvant chemotherapy alone versus adjuvant concurrent chemoradiotherapy (CCRT) as an alternative strategy for patients with early-stage (FIGO 2009 stage IB-IIA) cervical cancer having risk factors after surgery. The condition was assessed in terms of prognosis, adverse effects, and quality of life. This randomized trial involved nine centers across China. Eligible patients were randomized to receive adjuvant chemotherapy or CCRT after surgery. The primary end-point was progression-free survival (PFS). From December 2012 to December 2014, 337 patients were subjected to randomization. Final analysis included 329 patients, including 165 in the adjuvant chemotherapy group and 164 in the adjuvant CCRT group. The median follow-up was 72.1 months. The three-year PFS rates were both 91.9%, and the five-year OS was 90.6% versus 90.0% in adjuvant chemotherapy and CCRT groups, respectively. No significant differences were observed in the PFS or OS between groups. The adjusted HR for PFS was 0.854 (95% confidence interval 0.415-1.757; P = 0.667) favoring adjuvant chemotherapy, excluding the predefined non-inferiority boundary of 1.9. The chemotherapy group showed a tendency toward good quality of life. In comparison with post-operative adjuvant CCRT, adjuvant chemotherapy treatment showed non-inferior efficacy in patients with early-stage cervical cancer having pathological risk factors. Adjuvant chemotherapy alone is a favorable alternative post-operative treatment.
Female ; Humans ; Uterine Cervical Neoplasms/drug therapy* ; Prospective Studies ; Quality of Life ; Neoplasm Staging ; Chemoradiotherapy ; Chemotherapy, Adjuvant/adverse effects* ; Adjuvants, Immunologic ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Retrospective Studies

Objective:To investigate the neuroprotective effect of histone deacetylase 3 (HDAC3) specific inhibitor RGFP966 on traumatic brain injury (TBI) and its mechanism in rats.Methods:Forty-eight SD rats were randomly divided into sham-operated group, TBI group, TBI+vehicle group and TBI+RGFP966 group ( n=12). Rats in the later 3 groups accepted hydraulic impact brain injury to establish TBI models; and then, RGFP966 (dissolved in 1% DMSO at a dose of 10 mg/kg) was injected intraperitoneally 30 min after modeling, twice a day for 3 d, in TBI+RGFP966 group; same amount of DMSO was injected into TBI+vehicle group at the same time. Three d after modeling, neurological function was tested by modified neurological severity score (mNSS), water content of brain tissues was detected by dry-wet weight method, proportion of injured neurons at the frontal cortical tissues on the affected side was detected by Nissl staining, expressions of HDAC3 and pyroptosis related proteins were detected by immunohistochemical staining and Western blotting, and serum content of inflammatory factors was detected by ELISA. Results:Three d after modeling, compared with the TBI+vehicle group, the TBI+RGFP966 group had significantly decreased mNSS scores (9.83±0.75 vs. 6.67±0.82), water content of the injured cerebral cortex (82.73%±0.36% vs. 80.92%±0.66%), proportion of damaged neurons (75.60%±7.44% vs. 55.87%±4.10%), and HDAC3 protein expression (0.67±0.09 vs. 0.51±0.07), and significantly increased acetylated H3 (Ace-H3) and acetylated H4 (Ace-H4) protein expressions (0.81±0.02 vs. 1.22±0.02; 0.74±0.01 vs. 1.07±0.02), and statistically decreased protein expressions of nuclear factor-κB (NF-κB, 1.20±0.05 vs. 0.94±0.04), NOD-like receptor thermal protein domain associated protein 3 (NLRP3, 0.72±0.02 vs. 0.40±0.03), Caspase-1 containing cysteine (Caspase-1), dermatin D N-terminal fragment (GSDMD-N, 0.71±0.03 vs. 0.52±0.01), significantly decreased NF-κB and NLRP3 immunohistochemical staining scores, and significantly decreased serum contents of tumor necrosis factor-α, interleukin(IL)-1β and IL-18 ( P<0.05). Conclusion:Early intervention with RGFP966 after TBI can reduce the pyroptosis and inflammatory reaction of nerve cells and play neuroprotective role, whose mechanism may be related to inhibited activation of NF-κB/NLRP3/GSDMD pathway.

Objective To investigate the imaging features of primary Rosa-i Dorfman disease (RDD)in the central nervous system and to increase the understanding of the disease.Methods The MRI findings of 5 cases with primary RDD of the central nervous system were analyzed retrospectively,and the related literatures were reviewed.Results Four cases located in the cranium,1 case located in the spinal cord,and 5 tumors were attached to the brain (ridge)membrane.The tumor was equal and low signal on T1 WI,and equal or slightly high signal on T2 WI.Obvious enhancement could be seen on enhance study,and obvious enhancementwas visible in adjacent brain (ridge)membrane,in which 1 case involved the skull,with thickening and strengthening of the skull.Tumors were attached to the meninges in a wide range,the local meninges of 3 cases were penetrated by tumor.Conclusion If young and middle-aged males have no obvious specific clinical manifestations,the images of MRI are single or multiple lesions that are closely related to the brain (ridge)membrane in larger extent and easily penetrate the brain (ridge)membrane,the possibility of RDD should be considered.

Objective: To investigate the prognostic value of radiomics analysis in predicting axillary lymph nodes (ALN) metastasis of breast cancer based on dynamic contrast-enhanced MR imaging (DCE-MRI). Methods: One hundred and ninety-six patients with suspected breast cancer were prospectively collected for dynamic breast DCE-MRI. Enhanced MR imaging data of 72 axillary lymph nodes were evaluated separately by a chief radiologist and a resident, and the consistency analysis was performed. Lymph nodes were dichotomized according to the pathology results derived from operation or biopsy under real-time virtual sonography based on MRI data. Clinical and imaging data were also divided into corresponding groups. (Imaging) Data from both groups were respectively classified as training set and testing set by stratified sampling in proportion with 3∶1. AK software was applied to extract 6 major categories of 385 features (including histogram, morphology, texture parameters, gray level co-occurrence matrix, run-length matrix and grey level zone size matrix from imaging), and a set of statistically significant features were subsequently obtained by dimension reduction. The prediction model was established through binary classification logistic regression and employed to externally test the validation set by the method of confusion matrix. Meanwhile, ROC analysis was applied to assess the diagnostic performance of the model. Results: Of the 72 axillary lymph nodes, 35 were metastatic negative and 37 were positive. The consistency of enhanced MRI radiomics features was good, between 0.841 and 0.980. Uniformity, ClusterProminence_AllDirection_offset1_SD, Correlation_AllDirection_offset1, LongRunEmphasis_angle90_offset7 and SurfaceVolumeRatio were statistically significant differences (P<0.01), the area under the ROC between 0.747 and 0.931. In the training and testing group, the areas under the ROC, sensitivity, specificity and accuracy of the model were 0.953, 0.893, 0.926, 92.6% (50/54) and 0.944, 0.900, 1.000, 88.9% (16/18) respectively. Conclusion The prediction model based on radiomic features may provide a non-invasive and effective approach to the assessment of the risk of ALN metastasis of breast cancer.

OBJECTIVETo explore the application value of texture analysis of magnetic resonance images (MRI) in predicting the efficacy of neoadjuvant chemoradiotherapy(nCRT) for rectal cancer.

METHODSA total of 34 rectal cancer patients who were hospitalized at Zhejiang Provincial People's Hospital from February 2015 to April 2017 were prospectively enrolled and received 3.0T MRI examination at pre-nCRT (1 day before nCRT), early stage (at 10-day after nCRT) and middle stage (at 20-day after nCRT).

INCLUSION CRITERIAdistance from tumor lower margin to anal edge was less than 12 cm under rectoscope; rectal cancer was confirmed by preoperative pathology; clinical stage was T3 or above; lymph node metastasis existed but without distant metastasis; functions of liver, kidney and heart present no contraindications of operation.

EXCLUSION CRITERIAunfinished nCRT, surgery and three examinations of MRI; image motion artifacts; lack of postoperative pathological results. All the patients underwent rectal cancer long-term three-dimensional radiotherapy and chemotherapy combined with nCRT (oxaliplatin plus capecitabine). The tumor regression grading (TRG) was divided into TRG 0 to 4 grade after nCRT, and TRG 4 was classified as pathological complete remission (pCR); TRG 2 to 3 was classified as partial remission (PR); the rest was no remission (NR). Extraction and analysis of texture features in T2-weighted MR-defined tumor region were performed using Omni Kinetics texture software. The texture values of each time point were statistically analyzed, and the differences of texture values and change differences between pCR and PR+NR, and NR and pCR+PR were compared respectively. Statistically significant texture values were screened and were used in receiver operating characteristic (ROC) curve to assess the prediction of the efficacy of nCRT.

RESULTSOf 34 patients, 21 were males and 13 were females with median age of 49.3 years. Nineteen (55.9%) patients were low rectal adenocarcinoma and 15 (44.1%) patients were middle rectal adenocarcinoma. Nine (26.5%) cases belonged to pCR, 13 (38.2%) belonged to PR, and 12 (35.3%) belonged to NR. Before nCRT, the entropy of tumor area in pCR patients was significantly higher than that in PR+NR patients (7.164±0.272 vs. 6.823±0.309, t=2.925, P=0.006). At the middle stage of nCRT, as compared with PR+NR patients for the texture features of tumor region, the variance (1566±281 vs. 2883±867, t=-4.435, P=0.000) and entropy(5.436±0.934 vs. 6.803±0.577, t=-4.118,P=0.002) of pCR patients were significantly lower; kurtosis(4.800±1.288 vs. 3.206±1.211, t=3.333, P=0.002) and energy (0.016±0.005 vs. 0.010±0.004, t=3.240, P=0.003) of pCR patients were significantly higher. As compared to pCR+PR patients, the kurtosis(2.461±0.931 vs. 4.264±1.205, t=-4.493, P=0.000) and energy (0.011±0.004 vs. 0.014±0.004, t=-3.453, P=0.000) of the NR patients were significantly lower. As for texture change values between early stage and middle stage, the entropy difference was significant between pCR and PR+NR, NR and pCR+PR (1.344±0.819 vs. 0.489±0.319, t=3.047, P=0.014; 0.446±0.213 vs. 0.917±0.677, t=-3.638, P=0.001, respectively). As for texture change values between pre-nCRT and middle stage, variance and entropy differences between pCR and PR+NR (1759±1226 vs. 977±842, t=2.113, P=0.042; 1.728±0.918 vs. 0.524±0.355, t=3.832, P=0.004), and the change values of entropy between NR and pCR+PR (0.475±0.349 vs. 1.044±0.860, t=-2.722, P=0.011) were statistically significant. The above indicators were included in the ROC curve. The results revealed that at the middle stage, entropy value >5.983 indicated the best efficacy for the diagnosis of pCR, with the area under the ROC curve (AUC) of 0.885, the sensitivity of 100%, and the specificity of 66.7%; the energy <0.010 indicated the best AUC for diagnosis of NR was 0.902, with the sensitivity of 91.7% and specificity of 81.8%.

CONCLUSIONSTexture analysis based on T2 weighted images can predict the efficacy of nCRT for rectal cancer. The middle stage of nCRT is the best time of prediction. The entropy and energy of this period are texture parameters having higher predictive ability.

Chemoradiotherapy ; Female ; Humans ; Magnetic Resonance Spectroscopy ; Male ; Middle Aged ; Neoadjuvant Therapy ; Neoplasm Staging ; Predictive Value of Tests ; Prognosis ; Rectal Neoplasms ; diagnostic imaging ; therapy ; Treatment Outcome

Objective To explore the application of 64 slice low dose spiral CT in pediatric paranasal sinus examination.Methods Sixty children with paranasal sinuses were randomly divided into three groups(control group,low dose 1 group,low dose 2 group),and were given conventional dose scanning(100 KV in tube voltage,100 mA in tube current),low dose scanning(100 KV in tube voltage,45 mA in tube current),and low dose scanning (100KV in tube voltage,25 mA in tube current).The single scan weighted CT dose index (CTDIw) of each patient was recorded and compared;and the quality of the scanned images of each group was evaluated by two chief physicians by blind method.Results Compared with conventional dose group,low dose 1,2 groups had significantly lower CTDIw,and the dose decreased for 59.23％ and 72.42％ respectively.The image quality of the low-dose 1 group did not change significantly,and all the images could meet the requirements of clinical diagnosis;but the image quality of the low-dose 2 group decreased significantly,and the images of 3 patients could not meet the requirements of clinical diagnosis.Conclusion Appropriate reduction of scanning parameters for paranasal sinuses children can not only obtain good quality images,but also effectively reduce the radiation dose of patients.

Objective To explore the application of 64 slice low dose spiral CT in pediatric paranasal sinus examination.Methods Sixty children with paranasal sinuses were randomly divided into three groups(control group,low dose 1 group,low dose 2 group),and were given conventional dose scanning(100 KV in tube voltage,100 mA in tube current),low dose scanning(100 KV in tube voltage,45 mA in tube current),and low dose scanning (100KV in tube voltage,25 mA in tube current).The single scan weighted CT dose index (CTDIw) of each patient was recorded and compared;and the quality of the scanned images of each group was evaluated by two chief physicians by blind method.Results Compared with conventional dose group,low dose 1,2 groups had significantly lower CTDIw,and the dose decreased for 59.23％ and 72.42％ respectively.The image quality of the low-dose 1 group did not change significantly,and all the images could meet the requirements of clinical diagnosis;but the image quality of the low-dose 2 group decreased significantly,and the images of 3 patients could not meet the requirements of clinical diagnosis.Conclusion Appropriate reduction of scanning parameters for paranasal sinuses children can not only obtain good quality images,but also effectively reduce the radiation dose of patients.