China has largest number of chronic hepatitis C (CHC) patients, with complex distribution of genotypes, high proportion of refractory types and low diagnosis and treatment rate. It is necessary to explore accessible pan-genotype antiviral treatment protocols with high cure rate. Currently, the direct acting antiviral agents (DAAs) are recommended as the main treatment regimes by international guidelines for hepatitis C. Ravidasvir (RDV) is a new generation of NS5a inhibitor, which can be widely used in treatment of gene type 1, 2, 3, 4 and 6 CHC with strong antiviral activity and high resistance barrier. A number of clinical studies demonstrate that the combination of ravidavir with DAA S, such as second-generation protease inhibitor danoprevir (DNV) and nucleoside NS5b inhibitor sofosbuvir (SOF) have gained high cure rate and good safety for CHC patients. In this article, the results of related studies on ravidavir-based antiretroviral regimens in treatment of CHC are reviewed.

Objective To evaluate the inhibitive effect of tea polyphenol on the growth of human nasopharyngeal carcinoma HONE1 cell xenograft in nude mice ,and to explore the underlying mechanisms .Methods Tumor model was established by subcu‐taneous inoculation of nasopharyngeal carcinoma cell HONE1 into nude mice ,was used to evaluate the antitumor effect of tea poly‐phenol in vivo .The expression levels of VEGF were detected by real‐time PCR and western blot .Results The growth of xenograft in nude mice was significantly suppressed after application of tea polyphenol at a dose‐dependent manner .To compare with control group ,the inhibition rates were 18 .82% (P<0 .05) and 47 .66% (P<0 .05)when treated at low and high dose respectively ,With in‐creased concentration of TP ,the inhibition rates increased .Real‐time fluorescence quantitative‐PCR and western blot results showed that the expression of VEGF decreased at a dose‐dependent manner .The change of high dose group was obviously ,the difference was statistically significant(P<0 .05) .Conclusion Tea polyphenol could significantly inhibit the growth of human nasopharyngeal carcinoma HONE1 cell xenograft in nude mice ,probably by down regulating the VEGF protein level to inhibit tumor angiogenesis effects .

Objective To evaluate the effect of stellate ganglion block (SGB) on postoperative synaptic structure in hippocampal CA3 region in aged rats.Methods Seventy-two male Sprague-Dawley rats,aged 20-22 months,weighing 550-650 g,were randomly divided into 3 groups (n =24 each) using a random number table:control group (group C),operation group (group O) and SGB + operation group (group SGB).Group SGB received right SGB with 0.25％ bupivacaine 0.15 ml.Groups O and SGB underwent 30 min of exploratory laparotomy starting from 15 min after the end of administration.Y-maze test was performed on 1 day after operation in 6 rats chosen from each group for assessment of cognitive function.The frequency of standard training and standard time were recorded.Six rats were chosen from each group on 1,3 and 7 days after operation and sacrificed and the hippocampal CA3 region was isolated for microscopic examination and for measurement of synaptic structure.Results Compared with group C,the standard time was significantly prolonged,and the frequency of standard training was increased in groups O and SGB,the width of synaptic cleft was increased,the thickness of post-synaptic density was decreased,the length of active zones was shortened,and the curvature of the synaptic interface was decreased on 1,3 and 7 days after operation in group O (P ＜ 0.05),and no significant changes were found in each synaptic structure parameter in group SGB (P ＞ 0.05).Compared with group O,the standard time was significantly shortened,the frequency of standard training was decreased,the width of synaptic cleft was decreased,the thickness of the post-synaptic density was increased,the length of active zones was prolonged,and the curvature of the synaptic interface was increased on 1,3 and 7 days after operation in group SGB (P ＜ 0.05).Conclusion The mechanism by which SGB improves the postoperative cognitive dysfunction in aged rats may be related to inhibition of changes of synaptic structure in hippocampal CA3 region.

OBJECTIVE: To investigate the effect and mechanism of tea polyphenol (TP) on the proliferation, apoptosis, migration and invasion of nasopharyngeal carcinoma(NPC) cell line HONEl. METHOD: After treated with different concentration of tea polyphenol, CCK-8 assay, fluorescent staining, cell scratching assay and transwell assay were applied to detect the effect of tea polyphenol on the HONE1 cells. Furthermore, the expression of protein VEGF was investigated by flow cytometry assay. RESULT: It was found that tea polyphenol could inhibit NPC cell proliferation significantly in a dose-dependent manner, however, little impact was observed in normal nasopharyngeal epithelial cell line NP69. Furthermore, it was demonstrated by fluorescent staining assay that tea polyphenol could induce NPC cell apoptosis, and cell scratching assay and transwell assay showed that tea polyphenol could inhibit cell migration and invasion. CONCLUSION Tea polyphenol can significantly inhibit cell proliferation, induce cell apoptosis and decreased the migration and invasion ability of NPC cells in vitro. Tea polyphenol might be a tumor suppressor of NPC cells.
Apoptosis ; drug effects ; Carcinoma ; Cell Line, Tumor ; drug effects ; Cell Movement ; drug effects ; Cell Proliferation ; drug effects ; Humans ; Nasopharyngeal Carcinoma ; Nasopharyngeal Neoplasms ; pathology ; Polyphenols ; pharmacology ; Tea ; chemistry

Objective:To analyze the MRI characteristics of surgical resected renal angiomyolipoma (AML) smaller than 4 cm.Methods:A total of 112 patients with surgical pathology confirmed renal AML of which the maximum diameter was smaller than 4 cm were analyzed retrospectively in the First Medical Centre, Chinese PLA General Hospital from January 2014 to November 2020, 5 of which were epithelioid angiomyolipoma (EAML) patients. According to the presence or absence of visible fat in lesions on MRI, the lesions were divided into AML with fat group and AML without visible fat (AML wovf) group. The MRI features were evaluated, including maximum diameter, location, growth pattern, shape, beak sign, angular interface with renal parenchyma, pseudo-capsule, hemorrhage, cystic degeneration, coagulative necrosis, flowing void in the tumor, signal intensity and homogeneity on T 2WI and diffusion weighter imaging (DWI), the peak enhanced phase. The differences of maximum diameter of AML with fat and AML wovf were analyzed using Mann-Whitney U test, and the differences of MRI features were analyzed using χ 2 test or Fisher′s exact probability test. Results:There were 123 lesions found in 112 patients, and 96 lesions contained fat and 27 lesions were AML wovf. 82 lesions showed round and round-like shapes, 112 lesions showed exophytic growth pattern, 71 lesions with peak enhancement in corticomedullary phase. And the numbers of lesions with angular interface with renal parenchyma, beak sign, cystic degeneration, pseudo-capsule, hemorrhage were 30, 49, 1, 1, 1, respectively. There was no coagulative necrosis in all lesions. Compared with AML with fat, AML wovf was single lesion. The diameters of AML with fat and AML wovf were 2.5 (1.7, 3.5) and 1.8 (1.4, 2.3) cm respectively, with statistically significant difference ( Z=-2.80, P=0.005). In the AML with fat and AML wovf, 65 and 12 cases were heterogeneous in T 2WI, 44 and 5 lesions showed beak sign, 26 and 4 lesions showed angular interface with renal parenchyma, 57 and 10 cases were heterogeneous in DWI. And there were 5 and 6 lesions showed the endophytic, 44 and 8 lesions showed partly exophytic, 47 and 13 lesions showed exophytic in patterns of tumor growth respectively. The beak sign, homogeneous in T 2WI and DWI, patterns of tumor growth showed statistical differences in AML with fat and AML wovf (all P<0.05), and there was no significant difference in other features ( P>0.05). A total of 5 EAML patients were with 8 lesions. One patient had 4 lesions with fat, other patients had single lesion in which 2 lesions with fat, 2 lesions without visible fat. One lesion without visible fat showed hemorrhage. Conclusions:Surgical resected AML smaller than 4 cm is often exophytic round and round-like, enhanced in corticomedullary phase, showing angular interface with renal parenchyma and beak sign, with rare cystic degeneration, pseudo-capsule, hemorrhage and improbable coagulation necrosis. AML wovf is single smaller lesion which often shows endophytic growth pattern, and beak sign is infrequent. EAML seems to be present in two modes, multiple lesions with fat and AML wovf with hemorrhage.

Objective:To analyze the clinical characteristics of hereditary diffuse leukoencephalopathy with spheroids (HDLS).Methods:A retrospective analysis was performed. The clinical data of 2 patients with genetically conformed HDLS, admitted to our hospital in August 2020 and October 2021, were collected; and a literature search was conducted in domestic and foreign databases from January 2012 to January 2022 (enrolling a total of 48 patients with HDLS caused by colony-stimulating factor-1 receptor [ CSF1R] gene mutation). The population, clinical, imaging and gene mutation characteristics of these patients were summarized and analyzed. Results:(1) In these 50 patients, 20 were male and 30 were female, with onset age of (40.72±11.27) years; 40 patients (80.0%) had been misdiagnosed. (2) The most common first symptom and sign were progressive cognitive impairment (74.0%) and progressive dementia (80.0%). The patients in the middle and old aged group (≥40 years old, n=31) had significantly higher incidences of progressive cognitive impairment and Parkinson's-like symptom, and statistically lower incidence of muscle weakness as compared with those in the youth group (<40 years old, n=19, P<0.05). (3) The highest incidence of abnormal imaging findings was white matter lesions (100.0%), followed by cerebral atrophy (84.0%), ventricular enlargement (84.0%) and corpus callosum atrophy (60.0%). DWI examination was completed in 28 patients, and all patients showed persistent limitation of diffusion (100.0%). The most affected areas of white matter lesions were around the lateral ventricles, followed by the frontal-parietal occipital lobe, and corpus callosum. The incidence of abnormal signal of central semiovale in youth group was statistically higher than that in middle and old aged group ( P<0.05). (4) A total of 36 CSF1R gene mutations or possibly pathogenic mutations were identified in 50 patients, 21 of which were novel mutations reported for the first time. Of the 47 patients whose mutations were described in detail, 8 (17.0%) and 5 (10.6%) probands carried c. 2381T>C/p. I794T and c.2345G>A/p.R782H, respectively. Conclusions:The clinical manifestations of HDLS are diverse and lack of specificity. The most common first symptom and sign are progressive cognitive impairment and progressive dementia; however, the symptom spectrum and MRI imaging changes of white matter damage are related to age. MRI follow-up and targeted gene testing help reduce misdiagnosis and missed diagnosis of HDLS.

Objective:To analyze the clinical characteristics of hereditary diffuse leukoencephalopathy with spheroids (HDLS).Methods:A retrospective analysis was performed. The clinical data of 2 patients with genetically conformed HDLS, admitted to our hospital in August 2020 and October 2021, were collected; and a literature search was conducted in domestic and foreign databases from January 2012 to January 2022 (enrolling a total of 48 patients with HDLS caused by colony-stimulating factor-1 receptor [ CSF1R] gene mutation). The population, clinical, imaging and gene mutation characteristics of these patients were summarized and analyzed. Results:(1) In these 50 patients, 20 were male and 30 were female, with onset age of (40.72±11.27) years; 40 patients (80.0%) had been misdiagnosed. (2) The most common first symptom and sign were progressive cognitive impairment (74.0%) and progressive dementia (80.0%). The patients in the middle and old aged group (≥40 years old, n=31) had significantly higher incidences of progressive cognitive impairment and Parkinson's-like symptom, and statistically lower incidence of muscle weakness as compared with those in the youth group (<40 years old, n=19, P<0.05). (3) The highest incidence of abnormal imaging findings was white matter lesions (100.0%), followed by cerebral atrophy (84.0%), ventricular enlargement (84.0%) and corpus callosum atrophy (60.0%). DWI examination was completed in 28 patients, and all patients showed persistent limitation of diffusion (100.0%). The most affected areas of white matter lesions were around the lateral ventricles, followed by the frontal-parietal occipital lobe, and corpus callosum. The incidence of abnormal signal of central semiovale in youth group was statistically higher than that in middle and old aged group ( P<0.05). (4) A total of 36 CSF1R gene mutations or possibly pathogenic mutations were identified in 50 patients, 21 of which were novel mutations reported for the first time. Of the 47 patients whose mutations were described in detail, 8 (17.0%) and 5 (10.6%) probands carried c. 2381T>C/p. I794T and c.2345G>A/p.R782H, respectively. Conclusions:The clinical manifestations of HDLS are diverse and lack of specificity. The most common first symptom and sign are progressive cognitive impairment and progressive dementia; however, the symptom spectrum and MRI imaging changes of white matter damage are related to age. MRI follow-up and targeted gene testing help reduce misdiagnosis and missed diagnosis of HDLS.

Objectives:To investigate the effect of fat suppression (FS) T 2WI on the interobserver agreement and diagnostic performance of clear cell likelihood score version 2.0 (ccLS v2.0) for clear cell renal cell carcinoma (ccRCC). Methods:In this retrospective study, the MR images of 111 patients with pathologically confirmed small renal masses (SRM) from January to December 2021 were analyzed in the First Medical Centre, Chinese PLA General Hospital. Of the 111 SRM, 82 cases were ccRCC and 29 cases were non-ccRCC. Two radiologists independently assessed ccLS scores based on T 2WI signal intensity (hypointense, isointense, hyperintense) and other MRI features (ccLS-T 2WI). After a one-month interval, the ccLS scores were independently evaluated utilizing the frequency-selective saturation FS-T 2WI and other MRI features (ccLS-FS-T 2WI). Fisher′s exact test was used to compare the difference in SRM signal intensity on T 2WI and FS-T 2WI. The weighted Kappa test was performed to assess the interobserver agreement of the two radiologists, and differences in the weighted Kappa coefficients were compared using the Gwet consistency coefficient. Receiver operating characteristic curves were drawn to evaluate the diagnostic performance of ccLS-T 2WI and ccLS-FS-T 2WI in diagnosing ccRCC, and the area under the curve (AUC) was compared utilizing the DeLong test. Results:The signal intensity of 111 SRM on T 2WI and FS-T 2WI had statistically significant difference (χ 2=126.33, P<0.001), consistent in 88 cases (79.3%) and varied in 23 cases (20.7%). The weighted Kappa coefficient of ccLS-T 2WI was 0.57 (95%CI 0.45-0.69) between the two radiologists, and the weighted Kappa coefficient of ccLS-FS-T 2WI was 0.55 (95%CI 0.42-0.67), and the difference was not statistically significant ( t=-0.65, P=0.520). The AUC of ccLS-T 2WI for ccRCC diagnosis was 0.92 (95%CI 0.86-0.97), while the AUC of ccLS-FS-T 2WI for ccRCC diagnosis was 0.91 (95%CI 0.85-0.96), and the difference was not statistically significant ( Z=1.50, P=0.133). Conclusions:The interobserver agreement and diagnostic performance of ccLS v2.0 based on T 2WI and FS-T 2WI sequences for ccRCC are comparable, and FS-T 2WI is applicable for the clinical application of ccLS v2.0.

MALDI-MS is an emerging technique that enables rapid profiling of endogenous substances in a high throughput. Nevertheless, its application to metabolite analysis is often hindered by the presence of massive matrix background peaks using conventional matrices. Herein rhein was introduced as a novel matrix for MALDI-MS analysis of cation metabolites. Several strong and weak basic metabolites were measured using rhein. Compared to the previously reported ionless matrix NSA and conventional matrix CHCA, clean MALDI-MS spectra were obtained devoid of matrix signals. Subsequently, we applied this matrix to profile a biologically complex sample, mice intestinal contents. In addition, we have validated the applicability of rhein to MALDI-MS imaging, which allows for simultaneous mapping of hundreds of metabolites from single mouse ileum section. In summary, the discovery of rhein as a novel MALDI matrix enables efficient and reliable profiling and imaging of endogenous metabolites from biological samples with no matrix interferences, which will greatly promote the utility of MALDI-MS-based platform for metabolome studies.

Targeting cGAS-STING pathway is a promising strategy in tumor treatment. The pattern recognition receptor cGAS identifies dsDNA and catalyzes the formation of the second messenger 2'3'-cGAMP, activating the downstream interferons and pro-inflammatory cytokines through the adaptor protein STING. Notably, in tumor immune microenvironment, key components of cGAS-STING pathway are transferred among neighboring cells. The intercellular transmission under these contexts serves to sustain and amplify innate immune responses while facilitating the emergence of adaptive immunity. The membrane-based system, including extracellular vesicles transport, phagocytosis and membrane fusion transmit dsDNA, cGAMP and activated STING, enhancing the immune surveillance and inflammatory. The membrane proteins, including specific protein channel and intercellular gap junctions, transfer cGAMP and dsDNA, which are crucial to regulate immune responses. And the ligand-receptor interactions for interferons transmission amplifies the anti-tumor response. This review elaborates on the regulatory mechanisms of cell-to-cell communications of cGAS-STING pathway in tumor immune microenvironment. We further explore how these mechanisms modulate immunological processes and discuss potential interventions and immunotherapeutic strategies targeting these signaling cascades.