New protocol for contrast media reduction in atrial fibrillation ablation-planning CT with dual region of interest.

INTRODUCTION: Many patients with atrial fibrillation have impaired renal function, and therefore pre-operative CT for radiofrequency catheter ablation should minimize the use of contrast media. This study describes a dual-region-of-interest (D-ROI) protocol for the scanning of pulmonary veins and left atrium (PVs-LA) with less contrast media and optimized scan timing compared to the single-region-of-interest (S-ROI) protocol, without compromising image quality. METHODS: This study retrospectively included 100 patients who underwent PVs-LA CT between July 2019 and February 2022. The participants were divided into two groups: Those scanned using the S-ROI method (Group A, n = 50), and those scanned using the D-ROI method (Group B, n = 50). Descriptive statistical analysis of the contrast effect and scan timing was performed using quantitative and qualitative data collected from both groups of images. RESULTS: The contrast media dose was larger in group A than in group B (63.6 ± 10.1 mL vs. 45.6 ± 6.9 mL; p < 0.001). The CT values of the PVs-LA did not differ significantly between groups A and B [434.2 ± 77.0 Hounsfield units (HU) and 428.8 ± 77.2 HU, respectively; p = 0.73]. Two evaluators determined appropriate scan timing (when PVs-LA reached a relatively sufficient contrast effect for diagnosis) in 23 (46%) and 45 (90%) patients from groups A and B, respectively (p < 0.001). CONCLUSIONS: Although the radiation dose is slightly increased compared with the S-ROI method, the D-ROI method provides improved scan timing and images with similar contrast enhancement while reducing the amount of contrast medium administered. IMPLICATIONS FOR PRACTICE: The novel D-ROI bolus tracking technique can reduce the contrast medium dose while optimizing scan timing.

[Killing effect of anti-MSLN-iCAR-NK cells derived from induced pluripotent stem cells on ovarian epithelial cancer cells].

Objective: To investigate the cytotoxic effects of induced pluripotent stem (iPS) cells of anti-mesothelin (MSLN)-chimeric antigen receptor natural killer (CAR-NK) cells (anti-MSLN-iCAR-NK cells) on ovarian epithelial cancer cells. Methods: Twenty cases of ovarian cancer patients who underwent surgical treatment at Henan Provincial People's Hospital from September 2020 to September 2021 were collected, and 20 cases of normal ovarian tissues resected during the same period due to other benign diseases were also collected. (1) Immunohistochemistry and immunofluorescence were used to verify the expression of MSLN protein in ovarian cancer tissues. (2) Fresh ovarian cancer tissues were extracted and cultured to obtain primary ovarian cancer cells. Recombinant lentiviral vectors targeting anti-MSLN-CAR-CD244 were constructed and co-cultured with iPS cells to obtain anti-MSLN-iCAR cells. These cells were differentiated into anti-MSLN-iCAR-NK cells using cytokine-induced differentiation method. The cell experiments were divided into three groups: anti-MSLN-iCAR-NK cell group, natural killer (NK) cell group, and control group. (3) Flow cytometry and live cell staining experiment were used to detect the apoptosis of ovarian cancer cells in the three groups. (4) Enzyme-linked immunosorbent assay (ELISA) was used to measure the expression levels of interferon-γ (IFN-γ), tumor necrosis factor-α (TNF-α), granzyme B (GZMB), perforin 1 (PRF1), interleukin (IL)-6, and IL-10 in the three groups of ovarian cancer cells. Results: (1) Immunohistochemistry analysis showed that a positive expression rate of MSLN protein in ovarian cancer tissues of 65% (13/20), while normal ovarian tissues had a positive rate of 30% (6/20). The comparison between the two groups was statistically significant (χ2=4.912, P=0.027). Immunofluorescence analysis revealed that the positive expression rate of MSLN protein in ovarian cancer tissues was 70% (14/20), while normal ovarian tissues had a positive rate of 30% (6/20). The comparison between the two groups was statistically significant (χ2=6.400, P=0.011). (2) Flow cytometry analysis showed that the apoptotic rate of ovarian cancer cells in the anti-MSLN-iCAR-NK cell group was (29.27±0.85)%, while in the NK cell group and control group were (8.44±0.34)% and (6.83±0.26)% respectively. There were statistically significant differences in the comparisons between the three groups (all P<0.01). Live cell staining experiment showed that the ratio of dead cells to live cells in the anti-MSLN-iCAR-NK cell group was (36.3±8.3)%, while in the NK cell group and control group were (5.4±1.4)% and (2.0±1.3)% respectively. There were statistically significant differences in the comparisons between the three groups (all P<0.001). (3) ELISA analysis revealed that the expression levels of IFN-γ, TNF-α, GZMB, PRF1, IL-6, and IL-10 in ovarian cancer cells of the anti-MSLN-iCAR-NK cell group were significantly higher than those in the NK cell group and the control group (all P<0.05). Conclusion: The anti-MSLN-iCAR-NK cells exhibit a strong killing ability against ovarian cancer cells, indicating their potential as a novel immunotherapy approach for ovarian cancer.

[Predictive value of aMAP risk score for early recurrence of small hepatocellular carcinoma after microwave ablation].

Objective: To explore the value of the aMAP risk score (age, male, albumin-bilirubin, and platelets) to predict early recurrence within one year after microwave ablation in patients with small hepatocellular carcinoma. Methods: This was a retrospective study that enrolled 142 patients diagnosed with hepatocellular carcinoma who were treated with microwave ablation in the Department of Hepatology Unit of Nanfang Hospital, Southern Medical University from July 2016 to July 2021. The cohort enrolled 121 male and 21 female patients, including 110 patients that were <60 years old. All the patients were followed-up after microwave ablation to evaluate residual tumor and recurrence of tumor by computed tomography or magnetic resonance imaging. The observation indices mainly included general data and imaging data of patients. Using the X-tile tools, patients were divided into two groups: a high aMAP score group and a low aMAP score group. Multivariate Cox regression analysis was conducted for comparison of independent risk factors. Results: Multivariate Cox regression showed that high aMAP score, maximum tumor diameter >20 mm, and high AFP were the independent risk factors of early recurrence (all P<0.05). Kaplan-Meier survival curves showed that the median recurrence-free survival was 25.5 months in the low aMAP score group and 6.1 months in the high aMAP score group (P=0.001). Conclusions: The aMAP score could predict the early recurrence within 1 year of small hepatocellular carcinoma after microwave ablation. Patients with high aMAP score should undergo rigorous postoperative follow-up evaluations..

[Effects and mechanism of glycine on rat cardiomyocytes pretreated with serum from burned rats].

Objective: To investigate the effect and mechanism of glycine on rat cardiomyocytes pretreated with serum from burned rats (hereinafter referred to as burn serum). Methods: Experimental research methods were adopted. Thirty gender equally balanced Wistar rats aged 7 to 8 weeks were collected, 10 of which were used to prepare normal rat serum (hereinafter referred to as normal serum), and the other 20 were inflicted with full-thickness burn of 30% total body surface area to prepare burn serum. Primary cardiomyocytes were isolated and cultured from the apical tissue of 180 Wistar rats aged 1 to 3 days by either gender for follow-up experiments. Cells were divided into normal serum group and burn serum group treated with corresponding serum according to the random number table (the same grouping method below). Trypanosoma blue staining was performed at post treatment hour (PTH) 1, 3, 6, 9, and 12 to detect the cell survival rate. Cells were divided into burn serum alone group treated with burn serum for 6 h followed by routine culture of 30 min and 0.4 mmol/L glycine group, 0.8 mmol/L glycine group, 1.2 mmol/L glycine group, 1.6 mmol/L glycine group, and 2.0 mmol/L glycine group treated with burn serum for 6 h followed by culture of 30 min with corresponding final molarity of glycine, i.e., at post intervention hour (PIH) 6.5, the cell survival rate was detected as before. Cells were divided into normal serum group, burn serum alone group, 0.8 mmol/L glycine group, 1.2 mmol/L glycine group, and 1.6 mmol/L glycine group, with the same intervention of 6.5 h as before, respectively. The content of adenosine monophosphate (AMP) and adenosine triphosphate (ATP) was detected by high performance liquid chromatography, and the AMP/ATP ratio was calculated. The protein expressions of phosphorylated mammalian target of rapamycin complex 1 (p-mTORC1), phosphorylated p70 ribosomal protein S6 kinase (p-p70 S6K), phosphorylated eukaryotic translation initiation factor 4E-binding protein 1 (p-4E-BP1), and phosphorylated AMP-activated protein kinase (p-AMPK) were detected by Western blotting. Cells were divided into normal serum group, burn serum alone group, 0.8 mmol/L glycine group intervened as before and 0.8 mmol/L glycine+25 ng/mL rapamycin group treated with burn serum followed by culture with two reagents. The expressions of heat shock protein 70 (HSP70), metallothionein (MT), and tubulin were detected by immunofluorescence method after 30 min of corresponding culture at PTH 1, 3, and 6, i.e., at PIH 1.5, 3.5, and 6.5, and the microtubule morphology was observed at PIH 6.5. The sample number at each time point was 10. Data were statistically analyzed with analysis of variance for factorial design, one-way analysis of variance, least significant difference (LSD)-t test, LSD test, and Bonferroni correction. Results: At PTH 1, 3, 6, 9, and 12, the cell survival rates in burn serum group were significantly lower than those in normal serum group (with t values of 4.96, 16.83, 35.51, 34.33, and 27.88, P<0.05). In burn serum group, the cell survival rate at PTH 3, 6, 9, or 12 was significantly lower than that at PTH 1 (P<0.05), the cell survival rate at PTH 6, 9, or 12 was significantly lower than that at PTH 3 (P<0.05), and the cell survival rate at PTH 6 was similar to that at PTH 9 (P>0.05) but significantly higher than that at PTH 12 (P<0.05). Treatment of 6 h was selected as the follow-up intervention time of burn serum. At PIH 6.5, compared with that in burn serum alone group, the cell survival rate in each glycine group was significantly increased (P<0.05). The cell survival rate in 0.8 mmol/L glycine group was the highest, and 0.8, 1.2, and 1.6 mmol/L were selected as subsequent glycine intervention concentrations. At PIH 6.5, the AMP/ATP ratio of cells in burn serum alone group was significantly higher than that in normal serum group, 1.2 mmol/L glycine group, or 1.6 mmol/L glycine group (P values all <0.05), and the AMP/ATP ratio of cells in 1.6 mmol/L glycine group was significantly lower than that in 0.8 mmol/L glycine group (P<0.05). At PIH 6.5, the protein expressions of p-mTORC1, p-p70 S6K, and p-4E-BP1 of cells in normal serum group, burn serum alone group, 0.8 mmol/L glycine group, 1.2 mmol/L glycine group, and 1.6 mmol/L glycine group were 1.001±0.037, 0.368±0.020, 1.153±0.019, 1.128±0.062, 1.028±0.037, 0.96±0.07, 0.63±0.12, 1.17±0.13, 1.13±0.16, 1.11±0.11, and 0.98±0.06, 0.45±0.08, 1.13±0.05, 0.77±0.12, 0.51±0.13. Compared with those in burn serum alone group, the protein expressions of p-mTORC1, p-p70 S6K, and p-4E-BP1 of cells in normal serum group and each glycine group were significantly increased (P<0.05), while the protein expressions of p-AMPK were significantly decreased (P<0.05). Compared with those in 0.8 mmol/L glycine group, the protein expression of p-4E-BP1 of cells in 1.2 mmol/L glycine group and the protein expressions of p-mTORC1 and p-4E-BP1 of cells in 1.6 mmol/L glycine group were significantly decreased (P<0.05). Compared with those in 1.2 mmol/L glycine group, the protein expressions of p-mTORC1 and p-4E-BP1 of cells in 1.6 mmol/L glycine group were significantly decreased (P<0.05), while the protein expression of p-AMPK was significantly increased (P<0.05). Compared with those in normal serum group, the expression of tubulin of cells in burn serum alone group was significantly decreased at PIH 1.5, 3.5, and 6.5 (P<0.05), while the expression of HSP70 of cells at PIH 1.5 and 3.5 and the expression of MT at PIH 3.5 and 6.5 were significantly increased (P<0.05). The expressions of HSP70 and MT of cells at PIH 1.5, 3.5, and 6.5 and the expression of tubulin at PIH 1.5 and 3.5 in burn serum alone group and 0.8 mmol/L glycine+25 ng/mL rapamycin group were significantly lower than those in 0.8 mmol/L glycine group (P<0.05). At PIH 6.5, compared with that in normal serum group, the cell microtubule structure in burn serum alone group was disordered; the cell boundary in 0.8 mmol/L glycine group was clearer than that in burn serum alone group, and the microtubule structure arranged neatly near the nucleus. Compared with that in 0.8 mmol/L glycine group, 0.8 mmol/L glycine+25 ng/mL rapamycin group had unclear cell boundaries and disordered microtubule structure. Conclusions: Burn serum can cause cardiomyocytes damage in rats. Glycine can significantly up-regulate mammalian target of rapamycin/p70 ribosomal protein S6 kinase/eukaryotic translation initiation factor 4E-binding protein 1 signaling pathway through AMP-activated protein kinase, promote the synthesis of protective proteins HSP70, MT, and tubulin, stabilize the microtubule structure, and exert cardiomyocytes protection function.

Zetomipzomib (KZR-616) attenuates lupus in mice via modulation of innate and adaptive immune responses.

Zetomipzomib (KZR-616) is a selective inhibitor of the immunoproteasome currently undergoing clinical investigation in autoimmune disorders. Here, we characterized KZR-616 in vitro and in vivo using multiplexed cytokine analysis, lymphocyte activation and differentiation, and differential gene expression analysis. KZR-616 blocked production of >30 pro-inflammatory cytokines in human peripheral blood mononuclear cells (PBMCs), polarization of T helper (Th) cells, and formation of plasmablasts. In the NZB/W F1 mouse model of lupus nephritis (LN), KZR-616 treatment resulted in complete resolution of proteinuria that was maintained at least 8 weeks after the cessation of dosing and was mediated in part by alterations in T and B cell activation, including reduced numbers of short and long-lived plasma cells. Gene expression analysis of human PBMCs and tissues from diseased mice revealed a consistent and broad response focused on inhibition of T, B, and plasma cell function and the Type I interferon pathway and promotion of hematopoietic cell lineages and tissue remodeling. In healthy volunteers, KZR-616 administration resulted in selective inhibition of the immunoproteasome and blockade of cytokine production following ex vivo stimulation. These data support the ongoing development of KZR-616 in autoimmune disorders such as systemic lupus erythematosus (SLE)/LN.

Comparison of Pulmonary and Extrapulmonary Models of Sepsis-Associated Acute Lung Injury.

To compare different rat models of sepsis at different time points, based on pulmonary or extrapulmonary injury mechanisms, to identify a model which is more stable and reproducible to cause sepsis-associated acute lung injury (ALI). Adult male Sprague-Dawley rats were subjected to (1) cecal ligation and puncture (CLP) with single (CLP1 group) or two repeated through-and-through punctures (CLP2 group); (2) tail vein injection with lipopolysaccharide (LPS) of 10mg/kg (IV-LPS10 group) or 20 mg/kg (IV-LPS20 group); (3) intratracheal instillation with LPS of 10mg/kg (IT-LPS10 group) or 20mg/kg (IT-LPS20 group). Each of the model groups had a sham group. 7-day survival rates of each group were observed (n=15 for each group). Moreover, three time points were set for additional experimental studying in each model group: 4 hours, 24 hours and 48 hours after modeling (every time point, n=8 for each group). Rats were sacrificed to collect BALF and lung tissue samples at different time points for detection of IL-6, TNF-alpha, total protein concentration in BALF and MPO activity, HMGB1 protein expression in lung tissues, as well as the histopathological changes of lung tissues. More than 50 % of the rats died within 7 days in each model group, except for the IT-LPS10 group. In contrast, the mortality rates in the two IV-LPS groups as well as the IT-LPS20 group were significantly higher than that in IT-LPS10 group. Rats received LPS by intratracheal instillation exhibited evident histopathological changes and inflammatory exudation in the lung, but there was no evidence of lung injury in CLP and IV-LPS groups. Rat model of intratracheal instillation with LPS proved to be a more stable and reproducible animal model to cause sepsis-associated ALI than the extrapulmonary models of sepsis.

[Application of temporalis muscle flap in repair and reconstruction after the resection of tumor or necrotic foci following radiotherapy of nasopharyngeal carcinoma].

Objective: To summarize and popularize the application of temporalis muscle flap in repair and reconstruction after the resection of tumor or necrotic foci following radiotherapy of nasopharyngeal carcinoma (NPC). Methods: A retrospective analysis was made on the patients treated in the Department of Otorhinolaryngology Head and Neck Surgery of Xiangya Hospital between January 2019 and March 2021 who underwent surgical resection of tumor or necrosis of NPC after radiotherapy and temporalis muscle flap repair. The effect of the repair and the patients' postoperative conditions were analyzed. Results: A total 29 patients, 19 males and 10 females, aged from 33 to 65 years old, were included in the study, and were followed up for 6-35 months. Except for 2 patients who were not followed due to bleeding or special bacterial infection, the others' temporalis muscle flap healed well and no cerebrospinal fluid rhinorrhea or massive hemorrhage occurred. After the operation, all patients had no nasopharyngeal reflux or new open rhinolalia, and in some patients, the open rhinolalia even got relieved. Except for one case of depressed temporal fossa caused by infection and followed debridement and another one case of shallowed forehead wrinkles, the appearances of the other patients were basically symmetrical. Some patients had temporary mouth opening limitation after operation, and all of them recovered after rehabilitation exercises. Conclusions: The temporalis muscle flap can protect the skull base and internal carotid artery, and improve the quality of life of patients after the resection of NPC or necrotic foci. It is a reliable pedicled flap for repairing skull base defect with simple operation procedures and relatively few complications.

[Multi-omics research contributes to early screening, diagnosis and treatment of liver cancer].

In 2016, the World Health Organization set an ambitious goal of reducing viral hepatitis-related deaths by 65% by 2030. The key to this goal is to reduce viral hepatitis-related HCC deaths. Liver cancer is the fourth most common malignant tumor and the second leading cause of cancer death in China. The onset of HCC is insidious, and most patients are already in the middle and late stage when diagnosed. Despite the great progress on management of HCC, the therapeutic effect and prognosis of HCC are still unsatisfactory. Therefore, multi-dimensional and comprehensive analysis of the mechanism of liver cancer, improving the early screening, diagnosis and treatment rate of liver cancer are the key points of reducing the harm of liver cancer in China. In recent years, multi-omics studies have been widely applied in the field of liver cancer, providing a basis for the pathogenesis of liver cancer, early detection and diagnosis, development of individual treatment strategies and prognosis assessment. This issue will focus on the application of genomics, proteomics, metabolomics and imaging omics in early screening, diagnosis and treatment of liver cancer.

[Research advances of metabolomics in early diagnosis of hepatocellular carcinoma].

Primary liver cancer is the second leading cause of death from malignant tumors in China, and hepatocellular carcinoma (HCC) is the main type. The disease stage at the time of HCC diagnosis largely determines the efficacy of subsequent treatment. Due to the HCC screening among high-risk population has not yet popularized, and the current diagnose method of early HCC is not satisfactory, the early HCC diagnosis rate is less than 30% in China. Metabolomics research emerging in recent years has promoted the research progress of HCC in many fields, such as elaborating the mechanism of occurrence and development, early prevention and diagnosis, exploring drug treatment targets. At the same time, a large number of serum metabolites with excellent sensitivity and specificity were discovered, which made up for the deficiency of traditional serological indicators and helped the early screening and early diagnosis of HCC. This review will summarize the studies on serum metabolomic markers of HCC in recent 5 years, explore the role of metabolomics in the early prediction and diagnosis of HCC and its application prospect.

[PCGF1 is highly expressed in rectal adenocarcinoma and silencing PCGF1 inhibits proliferation of rectal adenocarcinoma cells in vitro].

OBJECTIVE: To investigate the expression of PCGF1 in rectal adenocarcinoma (READ) and the effect of PCGF1 silencing on proliferation READ cells in vitro. METHODS: The UALCAN and ENCORI online databases were used to analyze the expression level of PCGF1 in READ tissues and normal tissues and its association with the clinicopathological parameters and survival outcomes of patients with READ. The expression levels of PCGF1 were detected in two READ cell lines and a normal rectal epithelial cell line (HcoEpiC cells) using qPCR and Western blotting. Lentiviral vectors were used to construct PCGF1-overexpressing and PCGF1-silenced cell lines, and the proliferative activity of the cells was assessed using CCK-8 assay. The effect of PCGF1 silencing on tumor proliferation in vivo was also evaluated by observing tumorigenicity of the cells in nude mice. RESULTS: PCGF1 was highly expressed in READ tissue (P < 0.001), and its expression levels was correlated with READ stage, differentiation and lymph node metastasis (P < 0.001). A high PCGF1 expression level was associated with a poor survival outcome of READ patients (P < 0.05). In SW837 and SW1463 cells, PCGF1 silencing significantly lowered the proliferative activity of the cells both in vitro (P < 0.05) and in nude mice (P < 0.01). CONCLUSION: PCGF1 is highly expressed in READ tissue and may potentially serve as a prognostic biomarker as well as a therapeutic target for READ.

[Clinical characteristics of 272 437 patients with different histopathological subtypes of primary esophageal malignant tumors].

Objective: To characterize the histopathological subtypes and their clinicopathological parameters of gender and onset age by common, rare and sparse primary esophageal malignant tumors (PEMT). Methods: A total of 272 437 patients with PEMT were enrolled in this study, and all of the patients were received radical surgery. The clinicopathological information of the patients was obtained from the database established by the State Key Laboratory of Esophageal Cancer Prevention & Treatment from September 1973 to December 2020, which included the clinical treatment, pathological diagnosis and follow-up information of esophagus and gastric cardia cancers. All patients were diagnosed and classified by the criteria of esophageal tumor histopathological diagnosis and classification (2019) of the World Health Organization (WHO). The esophageal tumors, which were not included in the WHO classification, were analyzed separately according to the postoperative pathological diagnosis. The χ2 test was performed by the SPSS 25.0 software on count data, and the test standard α=0.05. Results: A total of 32 histopathological types were identified in the enrolled PEMT patients, of which 10 subtypes were not included in the WHO classification. According to the frequency, PEMT were divided into common (esophageal squamous cell carcinoma, ESCC, accounting for 97.1%), rare (esophageal adenocarcinoma, EAC, accounting for 2.3%) and sparse (mainly esophageal small cell carcinoma, malignant melanoma, etc., accounting for 0.6%). All the common, rare, and sparse types occurred predominantly in male patients, and the gender difference of rare type was most significant (EAC, male∶ female, 2.67∶1), followed with common type (ESCC, male∶ female, 1.78∶1) and sparse type (male∶ female, 1.71∶1). The common type (ESCC) mainly occurred in the middle thoracic segment (65.2%), while the rare type (EAC) mainly occurred in the lower thoracic segment (56.8%). Among the sparse type, malignant melanoma and malignant fibrous histiocytoma were both predominantly located in the lower thoracic segment (51.7%, 66.7%), and the others were mainly in the middle thoracic segment. Conclusion: ESCC is the most common type among the 32 histopathological types of PEMT, followed by EAC as the rare type, and esophageal small cell carcinoma and malignant melanoma as the major sparse type, and all of which are mainly occur in male patients. The common type of ESCC mainly occur in the middle thoracic segment, while the rare type of EAC mainly in the lower thoracic segment. The mainly sparse type of malignant melanoma and malignant fibrous histiocytoma predominately occur in the lower thoracic segment, and the remaining sparse types mainly occur in the middle thoracic segment.

Proteasome Inhibitors and Their Pharmacokinetics, Pharmacodynamics, and Metabolism.

The proteasome is responsible for mediating intracellular protein degradation and regulating cellular function with impact on tumor and immune effector cell biology. The proteasome is found predominantly in two forms, the constitutive proteasome and the immunoproteasome. It has been validated as a therapeutic drug target through regulatory approval with 2 distinct chemical classes of small molecular inhibitors (boronic acid derivatives and peptide epoxyketones), including 3 compounds, bortezomib (VELCADE), carfilzomib (KYPROLIS), and ixazomib (NINLARO), for use in the treatment of the plasma cell neoplasm, multiple myeloma. Additionally, a selective inhibitor of immunoproteasome (KZR-616) is being developed for the treatment of autoimmune diseases. Here, we compare and contrast the pharmacokinetics (PK), pharmacodynamics (PD), and metabolism of these 2 classes of compounds in preclinical models and clinical studies. The distinct metabolism of peptide epoxyketones, which is primarily mediated by microsomal epoxide hydrolase, is highlighted and postulated as a favorable property for the development of this class of compound in chronic conditions.

Plasma miR-146a and miR-365 expression and inflammatory factors in patients with osteoarthritis.

OBJECTIVE: To investigate the expression levels of micro-ribonucleic acid (miR)-146a and miR-365 in the plasma of osteoarthritis (OA) patients, to study their expression with the inflammatory factors and the severity of disease in patients and to analyse their diagnostic significance. MATERIALS AND METHODS: A total of 42 OA patients diagnosed with OA and treated in our hospital from January 2017 to January 2018 were selected as the subjects, and 28 healthy people were enrolled as controls. The expressions of interleukin-1 beta (IL-1ß) and IL-6 in the plasma of OA patients were detected via immunohistochemical staining. Moreover, the knee joint function of OA patients was evaluated by Lysholm score, Western Ontario and McMaster Universities (WOMAC) score and Visual Analogue Scale (VAS) score. The expression levels of plasma miR-146a and miR-365 in OA patients were measured through RT-PCR. Besides, the significance of the expression levels of miR-146a and miR-365 for the diagnosis of OA was analysed by ROC curves. RESULTS: As compared with healthy people, OA patients had elevated expression levels of plasma IL-1ß and IL-6, decreased Lysholm score, increased WOMAC and VAS scores as well as significantly up-regulated levels of plasma miR-146a and miR-365, which were of important significance for diagnosis. CONCLUSION: The expression levels of plasma miR-146a, miR-365 and inflammatory factors are notably higher, the disease is more severe, and the function of knee joint movement is weaker in OA patients than those in healthy controls. It can be concluded that the levels of both miR-146a and miR-365 can serve as biomarkers of OA diagnosis.

[Establishing an integrated hospital-community pyramid for screening and achieving hepatocellular carcinoma early diagnosis and treatment].

The comprehensive management of hepatocellular carcinoma (HCC) is a complete, dynamic and personalized process. Therefore, how to scientifically determine the HCC high-risk/extremely high-risk populations and develop a stratified monitoring plan is the key link to early detection, diagnosis and improvement of overall survival. In addition, accurately identifying high-risk/extremely high-risk groups based on the HCC risk prediction model, and applying it to establish an integrated hospital-community pyramid for HCC screening through the implementation of interdisciplinary scientific management and treatment may ultimately reduce HCC-related mortality rate.

[Application of aMAP score to assess the risk of hepatocarciongenesis in population of chronic liver disease in primary hospitals].

Objective: The aMAP score is a hepatocellular carcinoma (HCC) risk prediction model based on an international cooperative cohort, which can be applied to various liver diseases. The aim of this study is to use the aMAP score to stratify the risk of HCC in patients with chronic liver disease (combined or non-combined metabolic diseases) admitted to People's Hospital of Yudu County, Ganzhou City, Jiangxi Province, in order to guide personalized HCC screening. Methods: The demographic information, laboratory test results (platelets, albumin, and total bilirubin) and combined disease information of patients with chronic liver disease who were admitted to People's Hospital of Yudu from January 2016 to December 2020 were collected, and the aMAP score was calculated to stratify HCC risk in this population. Results: A total of 3629 cases with chronic liver disease were included in the analysis, including 3 452 (95.1%) cases with hepatitis B virus (HBV) infection, 177 (4.9%) cases with fatty liver, and 22 (0.6%) cases with HBV infection and fatty liver. There were 2 679 (73.8%) male and the median age was 44 (35, 54). In the overall population, low, medium and high risk of HCC accounted for 52.6%, 29.0%, and 18.4% respectively. In the HBV-infected population, the proportion of high risk of HCC was significantly higher than that of fatty liver (18.9% vs. 9.6%, P = 0.001). The proportion of chronic liver disease patients with combined hypertension or diabetes was significantly higher than that of those with non-combined metabolic diseases (combined hypertension: 32.3% vs. 17.9%, P < 0.001; combined diabetes: 36.5% vs. 18.1%, P < 0.001). Moreover, the proportion of high-risk population with two metabolic diseases was significantly higher than that with one and no metabolic diseases (40.9% vs. 31.8% vs. 17.7%, P < 0.001). Conclusion: The aMAP score can be used as a simple tool for HCC screening and management of chronic liver disease in primary hospitals, and it is helpful to improve the personalized follow-up management system of chronic liver disease population. Chronic liver disease patients with metabolic diseases have a higher risk of HCC, and people with high risk of HCC should be given special priority in follow-up visits, so as to improve the rate of HCC early diagnosis and reduce the mortality rate.

[New progress in the diagnosis and treatment of hepatocellular carcinoma: a decade of grinding sword].

Globally, hepatocellular carcinoma (HCC) is one of the most highly morbid, fatal, and malignant tumors, with a poor prognosis in advanced stage. In the past decade, new advances have been emerged in the field of HCC therapy, including surgery, ablation, transvascular intervention, external radiotherapy, and systemic therapy. Among them, systemic treatments, particularly targeted and immune checkpoint drugs have made outstanding progress, significantly improving the five-year survival rate of liver cancer patients. In addition, the management of liver cancer patients, especially the screening management and multidisciplinary collaborative diagnosis and treatment of high-risk populations, has significantly increased the early diagnosis rate and improved the overall treatment efficacy. Considering our country's condition and the development of existing treatment, the most effective strategy to reduce HCC mortality in the future is to accurately identify high-risk populations, increase the early diagnosis rate, and formulate personalized treatment strategies.

[Clinical study on endoscopic surgery for soft tissue necrosis of cranial base after radiotherapy for nasopharyngeal carcinoma].

Objective: To investigate the diagnosis and surgical treatment of patients with soft tissue necrosis of cranial base after radiotherapy for nasopharyngeal carcinoma (NPC). Methods: The clinical data of 7 NPC patients with soft tissue necrosis but not bone necrosis after radiotherapy were retrospectively analyzed.They were treated in Xiangya Hospital from 2015 to 2019. The clinical manifestations, diagnosis, treatment and prognosis were analyzed. The major clinical symptoms of the 7 patients were headache in 7 cases, hearing loss in 7 cases, long-term nasal malodor in 5 cases and epistaxis in 2 cases. All patients underwent high-resolution CT, MR and magnetic resonance angiography (MRA) before operation. All cases were treated with extended transnasal endoscopic approach under general anesthesia for resection of necrotic tissue. Five cases had their affected cartilaginous segments of the eustachian tubes partially or completely resected, 7 cases were treated with myringotomy and tube insertion, and 1 case was treated with pansinusectomy. Anti-inflammatory treatment were carried out during the perioperative period. The recovery of patients was observed and recorded through regular follow-up (from 6 months to 3 years) after the operation. Results: Nasopharynx soft tissue lesions can be seen in seven patients with bone cortex integrity by CT, and small bubble shadow can be seen at junction area between skull base soft tissue lesions and skull base bone surface.MR and MRA examination showed extensive inflammatory changes of nasopharynx. Parapharyngeal irregular necrotic cavity was found in 6 cases without central enhancement, demonstrating edema of surrounding soft tissue. The necrotic tissue of all 7 patients was surgically removed. Postoperative pathological examinations confirmed that all of them were necrotic soft and cartilaginous tissue, without tumor recurrence. The symptoms of all patients were significantly alleviated after operation. Headache was cured in 5 cases and relieved in 2 cases. Nasal malodor was cured in 4 cases and alleviated in 1 case. During the follow-up period, 5 patients survived, and 2 patients who had their eustachian tube reserved died. One of them died of nasopharyngeal hemorrhage caused by recurrent nasopharyngeal necrosis 3 months after the operation. Another case died of severe intracranial infection 6 months after operation. Conclusions: The diagnosis of skull base soft tissue necrosis after radiotherapy for nasopharyngeal carcinoma needs comprehensive analysis of radiotherapy history, clinical manifestations and imaging examination. High resolution CT, MR and MRA of skull base are very important for diagnosis. Early active removal of large-scale necrotic lesions under endoscope and partial or total resection of eustachian tube cartilage according to the involvement of eustachian tube cartilage is effective means of controling skull base soft tissue necrosis after radiotherapy. The effective means of necrosis can improve the quality of life of patients.

I125 irradiation stent for treatment of hepatocellular carcinoma with portal vein thrombosis: A meta-analysis.

PURPOSE: A meta-analysis aimed to systematically evaluate the safety and efficiency of I125 irradiation stent placement for patients with hepatocellular carcinoma (HCC) combined with portal vein tumor thrombosis (PVTT). MATERIALS AND METHODS: The Cochrane library, PubMed/Medline, EMBASE, CNKI, Wanfang Data and CQVIP were systematically screened out from the earliest to December 2019. The qualities of all included studies were assessed. The primary endpoints were the 6-month, 12-month stent cumulative patency rate and 6-month, 12-month, 24-month overall survival rate while the secondary endpoints were the objective response rate of PVTT, main portal venous pressure changes and treatment-related adverse events. Our meta-analysis was conducted using Stata 12.0 software. RESULTS: Totally seven studies with 1018 patients were included in the final analysis, in which 602 patients received TACE and I125 irradiation stent placement, and 416 patients in control group underwent TACE and stent placement without endovascular brachytherapy (EVBT). Meta-analysis showed that the I125 irradiation stent improved the cumulative stent patency rates in 6months [OR=1.65, 95% CI (1.32-2.05), P<0.001] and 12months [OR=2.55, 95% CI (1.90-3.42), P<0.001] and the survival rates in 6months [OR=1.77, 95% CI (1.41-2.22), P<0.001], 12months [OR=3.14, 95% CI (2.24-4.40), P<0.001] and 24months [OR=7.39, 95% CI (3.55-15.41), P<0.001]. However, there was no difference in the objective response rate of PVTT [OR=1.13, 95% CI (0.87-1.48), P=0.365], main portal venous pressure and the occurrence adverse event [OR=0.88, CI=0.72-1.08, P=0.212] between two groups. CONCLUSION: I125 irradiation stent seems to be more effective in treating hepatocellular carcinoma with portal vein tumor thrombosis. The usage of portal vein stent combined endovascular brachytherapy has the potential to act as an alternative therapy for HCC with PVTT. On account of the limitation of studies included, more studies with high-level evidence, such as RCTs, are requisite to support the above promising results.

Discovery and Early Clinical Development of Selective Immunoproteasome Inhibitors.

Inhibitors of the proteolytic activity of the 20S proteasome have transformed the treatment of multiple B-cell malignancies. These agents have also been employed with success in the treatment of patients with autoimmune diseases and immune-mediated disorders. However, new agents are needed to fully unlock the potential of proteasome inhibitors as immunomodulatory drugs. The discovery that selective inhibitors of the immunoproteasome possess broad anti-inflammatory activity in preclinical models has led to the progression of multiple compounds to clinical trials. This review focuses on the anti-inflammatory potential of immunoproteasome inhibition and the early development of KZR-616, the first selective inhibitor of the immunoproteasome to reach clinical testing.

Effects of the FABP4 gene on steroid hormone secretion in goose ovarian granulosa cells.

1. To investigate the physiological role of FABP4 in the goose ovary, this study determined the effects of overexpressing and siRNA interfering FABP4 on progesterone (P4) and oestradiol (E2) production in granulosa cells. Measurements were made by ELISA, real-time qRT-PCR and western blotting. 2. The concentrations of P4 and E2 in the FABP4 overexpression granulosa cells were increased compared to the control group (P > 0.05 for P4; P < 0.05 for E2). Likewise, the mRNA and protein expression levels of CYP11A1 and CYP19A1 were significantly higher than in the control group (P < 0.05 or P < 0.001). Conversely, the concentrations of P4 and E2 in the FABP4 silencing granulosa cells were significantly decreased compared with the control group (P < 0.001). Likewise, the mRNA and protein expression levels of CYP11A1 and CYP19A1 were significantly lower than in the control group (P < 0.001, or P < 0.01). 3. The study indicated that the FABP4 gene may regulate steroid hormone secretion and the expression of the steroidogenic genes in geese ovarian granulosa cells. These results support the possibility that the FABP4 gene mediates ovarian steroid hormone biosynthesis function and reproduction in geese.