Functional magnetic resonance imaging for staging chronic kidney disease: a systematic review and meta-analysis.

INTRODUCTION: The commonly used clinical indicators are not sensitive and comprehensive enough to evaluate the early staging of chronic kidney disease (CKD). This study aimed to evaluate the differences in arterial spin labeling (ASL) and blood oxygenation level-dependent functional magnetic resonance imaging (BOLD-MRI) parameter values among patients at various stages of chronic kidney disease and healthy individuals. METHODS: Electronic databases PubMed, Web of Science, Cochrane, and Embase were searched from inception to March 29, 2024, to identify relevant studies on ASL and BOLD in CKD. The renal blood flow (RBF) and apparent relaxation rate (R2*) values were obtained from healthy individuals and patients with various stages of CKD. The meta-analysis was conducted using STATA version 12.0. The random-effects model was used to obtain estimates of the effects, and the results were expressed as 95% confidence intervals (CIs) and mean differences (MDs) of continuous variables. RESULTS: A total of 18 published studies were included in this meta-analysis. The cortical RBF and R2* values and medulla RBF values were considerably distinct between patients with various stages of CKD and healthy controls (MD, - 78.162; 95% CI, - 85.103 to - 71.221; MD, 2.440; 95% CI, 1.843 to 3.037; and MD, - 36.787; 95% CI, - 47.107 to - 26.468, respectively). No obvious difference in medulla R2* values was noted between patients with various stages of CKD and healthy controls (MD, - 1.475; 95% CI, - 4.646 to 1.696). CONCLUSION: ASL and BOLD may provide complementary and distinct information regarding renal function and could potentially be used together to gain a more comprehensive understanding of renal physiology.

Elucidating immune cell dynamics in chronic lung allograft dysfunction: A comprehensive single-cell transcriptomic study.

Chronic Lung Allograft Dysfunction (CLAD) is a critical post-transplant complication that predominantly determines the long-term survival rates and quality of life of patients undergoing lung transplantation. The limited efficacy of current immunosuppressive strategies underscores our incomplete understanding of the immunological aspects of CLAD. Hence, there is an urgent need for more comprehensive and targeted research to unravel the complex interplay of immune cells in the development and progression of CLAD. This study conducts an in-depth analysis of the immune environment in CLAD. By examining the gene expression profiles of T cells, natural killer cells, B cells, macrophages, and monocytes, we have elucidated a unique immunological landscape in CLAD compared to healthy controls. We highlight the heterogeneity within the immune populations and provide a comprehensive understanding of the immune mechanisms driving CLAD. Enrichment analysis identified specific pathways that are either overactive or suppressed in CLAD, revealing potential molecular targets for therapeutic intervention. Our findings emphasize the crucial role of T cells in the pathophysiology of CLAD, coordinating the immune response and revealing an amplified immune cell network, potentially leading to maladaptive tissue responses. By integrating a comprehensive cellular and molecular portrait of the immune environment, our research not only deepens our understanding of the pathogenesis of CLAD but also lays a foundational approach for the development of targeted therapies.

Radiogenomics study to predict the nuclear grade of renal clear cell carcinoma.

Purpose: To develop models based on radiomics and genomics for predicting the histopathologic nuclear grade with localized clear cell renal cell carcinoma (ccRCC) and to assess whether macro-radiomics models can predict the microscopic pathological changes. Method: In this multi-institutional retrospective study, a computerized tomography (CT) radiomic model for nuclear grade prediction was developed. Utilizing a genomics analysis cohort, nuclear grade-associated gene modules were identified, and a gene model was constructed based on top 30 hub mRNA to predict the nuclear grade. Using a radiogenomic development cohort, biological pathways were enriched by hub genes and a radiogenomic map was created. Results: The four-features-based SVM model predicted nuclear grade with an area under the curve (AUC) score of 0.94 in validation sets, while a five-gene-based model predicted nuclear grade with an AUC of 0.73 in the genomics analysis cohort. A total of five gene modules were identified to be associated with the nuclear grade. Radiomic features were only associated with 271 out of 603 genes in five gene modules and eight top 30 hub genes. Differences existed in the enrichment pathway between associated and un-associated with radiomic features, which were associated with two genes of five-gene signatures in the mRNA model. Conclusion: The CT radiomics models exhibited higher predictive performance than mRNA models. The association between radiomic features and mRNA related to nuclear grade is not universal.

Artificial intelligence with magnetic resonance imaging for prediction of pathological complete response to neoadjuvant chemoradiotherapy in rectal cancer: A systematic review and meta-analysis.

Purpose: The purpose of this study was to evaluate the diagnostic accuracy of artificial intelligence (AI) models with magnetic resonance imaging(MRI) in predicting pathological complete response(pCR) to neoadjuvant chemoradiotherapy (nCRT) in patients with rectal cancer. Furthermore, assessed the methodological quality of the models. Methods: We searched PubMed, Embase, Cochrane Library, and Web of science for studies published before 21 June 2022, without any language restrictions. The Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2) and Radiomics Quality Score (RQS) tools were used to assess the methodological quality of the included studies. We calculated pooled sensitivity and specificity using random-effects models, I2 values were used to measure heterogeneity, and subgroup analyses to explore potential sources of heterogeneity. Results: We selected 21 papers for inclusion in the meta-analysis from 1562 retrieved publications, with a total of 1873 people in the validation groups. The meta-analysis showed that AI models based on MRI predicted pCR to nCRT in patients with rectal cancer: a pooled area under the curve (AUC) 0.91 (95% CI, 0.88-0.93), sensitivity of 0.82(95% CI,0.71-0.90), pooled specificity 0.86(95% CI,0.80-0.91). In the subgroup analysis, the pooled AUC of the deep learning(DL) model was 0.97, the pooled AUC of the radiomics model was 0.85; the pooled AUC of the combined model with clinical factors was 0.92, and the pooled AUC of the radiomics model alone was 0.87. The mean RQS score of the included studies was 10.95, accounting for 30.4% of the total score. Conclusions: Radiomics is a promising noninvasive method with high value in predicting pathological response to nCRT in patients with rectal cancer. DL models have higher predictive accuracy than radiomics models, and combined models incorporating clinical factors have higher diagnostic accuracy than radiomics models alone. In the future, prospective, large-scale, multicenter investigations using radiomics approaches will strengthen the diagnostic power of pCR. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42021285630.

The comparative effects of sacubitril/valsartan versus enalapril on pulmonary hypertension due to heart failure with a reduced ejection fraction.

The purpose of this study was to investigate the effects of sacubitril/valsartan on right ventricular (RV) function in patients with pulmonary hypertension (PH) due to heart failure with reduced ejection fraction (HFrEF). We prospectively enrolled patients with HFrEF-induced PH admitted to the Department of Cardiology between August 2018 and December 2019. Patients were randomized to receive oral treatment with sacubitril/valsartan or enalapril. Epidemiological data were recorded before treatment. Echocardiography was performed at admission and 6 months of follow-up, and all parameters were compared. Major adverse cardiac events (MACEs) were compared between baseline and 6 months follow-up. There were no significant differences in the baseline characteristics between the two groups. After 6 months of treatment, both treatment groups improved the following parameters from baseline (mean ± SD): left atrium, left ventricle, the left ventricular ejection function (LVEF), RV systolic function (the tricuspid annular plane systolic excursion [TAPSE], the systolic pulmonary artery pressure [sPAP], and TAPSE/sPAP). After 6 months, sacubitril/valsartan improved significantly the following parameters compared with enalapril (all p < 0.05): LVEF (47.07 ± 6.93% vs. 43.47 ± 7.95%); TAPSE (15.33 ± 1.31 vs. 14.78 ± 1.36 mm); sPAP (36.76 ± 14.32 vs. 42.26 ± 12.07 mmHg); and TAPSE/sPAP ratio (0.50 ± 0.23 vs. 0.39 ± 0.14), respectively. There was no difference in readmissions due to recurrent heart failure. Sacubitril/valsartan seems to provide more beneficial effects among patients with HFrEF-induced PH to improve RV function, along with a decrease in pulmonary pressure.

Effectiveness of Trastuzumab Combined With Capecitabine Treatment in a Patient With Hilar Cholangiocarcinoma Complicated by Liver Metastases With an ERBB2-Activating Mutation: A Case Report.

The identification of ERBB2 (HER2) alteration in some solid tumors has become critically important due to the actionable events predictive of response to anti-HER2 therapy. However, the efficacy of ERBB2 mutated hilar cholangiocarcinoma (hCCA) against ERBB2 is rarely reported. Here we report a 76-year-old female diagnosed with hCCA complicated by liver metastases after radical resection. The next-generation sequencing assay showed that the tumor had an ERBB2 mutation. Then, the patient was treated with trastuzumab plus capecitabine. After 2 months of treatment, she had a partial response. Until now, the patient is still alive. This study has shown the potential of trastuzumab combined with capecitabine as an effective treatment for hilar cholangiocarcinoma complicated by liver metastases harboring ERBB2 alterations.

Knockdown of circ_0008344 contributes to radiosensitization in glioma via miR-433-3p/RNF2 axis.

Numerous studies have identified that circular RNAs (circRNAs) functioned as important regulators in tumor initiation, carcinogenesis, drug or radiation resistance. This study aims to reveal the function of circ_0008344 on radiosensitivity in glioma. The quantitative real-time polymerase chain reaction (qRT-PCR) was implemented for detecting the circ_0008344 and microRNA-433-3p (miR-433-3p) levels. Cell survival intensity and apoptosis were analyzed through colony formation assay and flow cytometry respectively. The protein levels were examined via Western blot. Dual-luciferase reporter assay was exploited for the analysis of target combination. Xenograft models were established in mice for circ_0008344 research in vivo. Our data showed that circ_0008344 level was signally increased in radioresistant glioma tissues and its down-regulation facilitated the susceptibility of glioma cells to radiation. Additionally, we found that circ_0008344 could interact with miR-433-3p and regulated radiosensitivity of glioma cells via sponging miR-433-3p. Ring finger protein 2 (RNF2) was proved to be a target of miR-433-3p and it was regulated by circ_0008344/miR-433-3p axis. The promotion of circ_0008344 knockdown on radiosensitivity was counteracted by RNF2 overexpression in glioma cells. Further experiment in vivo indicated that circ_0008344 down-regulation inhibited glioma growth and acted on miR-433-3p/RNF2 axis to enhance the radiosensitivity in glioma. These evidences manifested that knockdown of circ_0008344 exerted the radiosensitivity-promoting effect on glioma via the miR-433-3p-mediated RNF2 down-regulation, identifying circ_0008344 as a novel diagnostic biomarker of radioresistance and therapeutic target in glioma radiotherapy.

Splenectomy with Portoazygous Disconnection for Correction of Systemic Hemodynamic Disorders in Hepatic Cirrhosis Patients with Portal Hypertension: A Prospective Single-Center Cohort Study.

Objective: To investigate the effect of splenectomy for correction of systemic hemodynamic disorders in hepatic cirrhosis patients with portal hypertension. Methods: Hepatic cirrhosis patients with portal hypertension were enrolled from April 2015 to July 2018. Systemic hemodynamic parameters (heart rate, mean arterial pressure (MAP), cardiac output, and total peripheral vascular resistance (TPR)) were prospectively measured at baseline and 1 week, 1, 3, and 6 months, and 1, 2, and 3 years postoperatively. Paired analysis was conducted. Results: Sixty-nine patients were eligible, and 55 (79.7%) cases had a history of upper gastrointestinal bleeding. Child-Pugh classification was grade A in 41 (59.4%) cases, grade B in 26 (37.7%) cases, and grade C in 2 (2.9%) cases. The heart rate was significantly higher at 1 week postoperatively versus the baseline (P < 0.001). Meanwhile, the heart rate was significantly lower from 3 months to 2 years postoperatively versus the baseline (P < 0.05). The MAP was significantly higher at 6 months to 2 years postoperatively versus the baseline (P < 0.05). At 1 month postoperatively and 6 months to 2 years, the cardiac output was significantly lower versus the baseline (P < 0.05). At 1 month postoperatively and 6 months to 2 years, the TPR was significantly higher versus the baseline (P < 0.05). Conclusion: Splenectomy corrects systemic hemodynamic disorder in hepatic cirrhosis patients with portal hypertension, and the effect is rapid and durable.

The Effect of Splenectomy on the Reversal of Cirrhosis: a Prospective Study.

BACKGROUND: Studies have demonstrated that liver fibrosis can be reversed by medication treatments. After splenectomy, cirrhosis patients have short-term changes in several serum markers for cirrhosis and liver stiffness. AIMS: To investigate the effect of splenectomy on the severity of cirrhosis. METHODS: A total of 62 patients with cirrhosis and portal hypertension receiving splenectomy from December 2014 to July 2017 were enrolled. The degree of cirrhosis was preoperatively and postoperatively evaluated by serum markers, including hyaluronan (HA), laminin, amino-terminal propeptide of type III procollagen (PIIINP), type IV collagen (C-IV), liver stiffness (FibroScan), and liver volume. RESULTS: HA levels significantly increased at 1 week and 1 month postoperation (both P < 0.05), whereas the levels of PIIINP and C-IV significantly decreased from 1 month to 12 months postoperation (all P < 0.05). In addition, elastography examination demonstrated that the FibroScan score significantly reduced from 1 month to 24 months postoperation as compared with the baseline level (all P < 0.05). CT scan showed that the liver volume significantly increased at 6 months postoperation (P < 0.05). Furthermore, the alteration trends of these serum markers and the FibroScan score were further confirmed by the multivariate linear regression. CONCLUSIONS: These observations suggested that splenectomy may result in long-term reversal of cirrhosis.

SB203580 inhibits epithelial-mesenchymal transition and pulmonary fibrosis in a rat silicosis model.

To investigate the role of p38 MAPK in silicosis, we explored the effects of SB203580 as a specific inhibitor of p38 MAPK in the silicosis model in rats. Rats were exposed to 50mg/ml silica intratracheally. From the first day after instillation, rats were injected with SB203580 1mg/kg/d. Rats were sacrificed at 7 and 15days after exposure of silica. The results demonstrated SB203580 could prevent the activation of p38. TGF-ß1 in bronchoalveolar lavage fluid, the expression of vimentin and α-SMA in the lung tissue was down-regulated and E-cadherin was up-regulated after intervention with SB203580 at 7days and 15days. The percentage of the cells staining with SP-C and vimentin doubly was lower in SB203580 treated group than in silica group at 7days and 15days. SB203580 also inhibited the increase of ZEB-1, ZEB-2 and Twist at 7days. Histopathologic examination showed the decrease in the number of nodules and the blue areas of collagen fibers in the lung after SB203580 treatment. The content of hydroxyproline and the expression of collagen I and III decreased in SB203580 treated group than in silica group. These results suggested that p38 MAPK/ZEB-1 (ZEB-2, Twist) pathway was involved at 7days after silica instillation and p38 MAPK was pivotal for EMT in silicosis fibrosis in rats.

Gender differences in recovery consequences among heroin dependent patients after compulsory treatment programs.

Studies on recovery patterns and how baseline factors influence recovery consequences among heroin dependent patients have shown mixed results. This study is aimed at describing the gender differences in long-term recovery patterns and exploring the predictors of negative recovery consequences by gender among heroin dependent patients in Shanghai, China. At baseline, this study recruited 503 heroin dependent patients discharged from Shanghai compulsory rehabilitation facilities in 2007 and 2008. In this cohort study, the baseline data was then linked with participants' 5-year follow-up data from official records. Generalized Estimating Equations (GEE) were used to compare males with females in terms of the presence of negative consequences (incarceration, or readmission to compulsory treatment, or both), in the subsequent 5-years after their discharge from compulsory treatment. Ordinary least squares (OLS) regression was used to explore factors associated to the time length of negative consequences in 5 years after the discharge for males and females separately. Our findings indicate that female heroin dependent patients tend to have less negative recovery outcomes than male patients. Male patients with a life-time history of poly drug use and female patients with borderline personality disorder are especially at risk of incarceration and readmission into compulsory treatment programs.

Increased Neutrophil-Lymphocyte Ratio Is a Poor Prognostic Factor in Patients with Esophageal Cancer in a High Incidence Area in China.

BACKGROUND AND AIMS: Neutrophil-lymphocyte ratio (NLR) and the platelet-lymphocyte ratio (PLR) have been assumed to be a marker to predict the survival of patients with different types of cancer. We undertook this study to verify the prognostic value of the NLR and the PLR for predicting the survival rate of patients with esophageal cancer in a high incidence area in China. METHODS: In total, 820 cases from a high incidence area that had pathologically confirmed esophageal cancers initially diagnosed at the Fourth Hospital of Hebei Medical University from 2007-2008 were analyzed. The medical record system was used to collect patient information regarding personal details, cancer type, treatment, and routine blood examinations at the time of admission. Follow-up evaluations were conducted by the established follow-up system at the hospital. We used Kaplan-Meier method to calculate overall survival (OS) rate. We used Cox regression analysis to analyze the factors that may affect the OS rate of the patients. SPSS 13.0 and Excel software packages were used for statistical analysis. RESULTS: In total, 864 cases were consistent with the inclusion criterion. At the end of the study, 820 cases received follow-up evaluation. Follow-up rate was 94.91%. Among the 820 cases, 334 died of esophageal cancer, whereas 486 remain alive as of March 15, 2014. Five-year OS rate of the patients with esophageal cancer was 40.66%. Patients in the NLR ≥3.5 group demonstrated shorter OS than patients in the NLR <3.5 group (53.2 vs. 33.4 months, p = 0.001). Multivariate analysis indicated that age, pathological type, TNM stage, surgery and NLR were all independent risk factors for esophageal cancer. OR of NLR ≥3.5 group was 1.287 (1.049-1.580). CONCLUSIONS: NLR may be an independent prognostic factor for esophageal cancer in high incidence areas.

Structural modifications of 5,6-dihydroxypyrimidines with anti-HIV activity.

A series of 5,6-dihydroxypyrimidine analogs were synthesized and evaluated for their anti-HIV activity in vitro. Among all of the analogs, several compounds exhibited significant anti-HIV activity, especially 1b and 1e, which showed the most potent anti-HIV activity with EC(50) values of 0.14 and 0.15 µM, and TI (therapeutic index) values of >300 and >900, respectively. Further docking studies revealed that the representative compounds 1e and 3a could meet the HIV-1 integrase inhibition minimal requirements of a chelating domain (two metal ions) and an aromatic domain (π-π stacking interactions).

Prognostic significance of Bcl-xL gene expression in human colorectal cancer.

Bcl-xL is a pro-survival member of the Bcl-2 family that plays indispensable roles in regulating cell survival and apoptosis. It is overexpressed in many malignant tumors including colorectal cancer (CRC). However, it is still unclear if Bcl-xL can be used as an independent molecular marker for predicting the prognosis of CRC patients. In this study, reverse transcription-PCR assay was performed to detect the expression of Bcl-xL mRNA in CRC and corresponding non-tumor colon tissues. Immunohistochemistry was performed to detect the immunolocalization of Bcl-xL protein in sixty-eight primary CRC tissue samples. The association between Bcl-xL protein expression and clinicopathological factors of CRC patients was analyzed and the survival was assessed by the Kaplan-Meier method and proportional hazards model. The averaged level of Bcl-xL mRNA expression in CRC tissues (0.85±0.13) was significantly higher than that in non-tumor colon tissues (0.08±0.02). Immunohistochemical staining showed that the Bcl-xL protein was mainly located in the cytoplasm of tumor cells. The level of Bcl-xL protein expression was closely correlated with tumor differentiation (P=0.002), lymph node metastasis (P=0.010), venous permeation (P=0.004), and Duke's classification (P=0.021). Furthermore, patients with high Bcl-xL expression showed poorer overall survival than those with low Bcl-xL expression (P=0.016). Univariate and multivariate analysis indicated that the status of Bcl-xL protein expression might be an independent prognostic marker for CRC patients (P=0.032). Taken together, immunohistochemical assessment of status of Bcl-xL protein may offer a valuable approach for predicting survival after curative surgery for colorectal cancer.

Echocardiographic evaluation of cardiac rhabdomyoma in infants and children.

PURPOSE: The objective of this study was to demonstrate the clinical presentation, echocardiographic findings, and morbidity and mortality rates for cardiac rhabdomyoma in Chinese infants and children by using echocardiography. METHODS: Two-dimensional echocardiography was performed at our institution from 1992 through 1999 on 12,800 children under 15 years of age. The diagnoses of cardiac rhabdomyoma were made primarily by echocardiography based on the presence of multiple tumors, cardiac tumors associated with tuberous sclerosis (TS), or histopathologic examination of surgical specimens. All patients were evaluated with 2-dimensional and Doppler echocardiography and then on follow-up examination every 3-6 months. Complete tumor regression was defined as no tumor visible by echocardiography. Partial tumor regression was defined as a decrease in tumor size of at least 15% from the previously measured size. RESULTS: A total of 29 tumors were found in 11 patients, 8 of whom had either TS or a family history of TS in 1 or more first-degree relatives. There were 9 boys and 2 girls 1 day-6.5 years old; (mean, 1.1 years). Three patients (newborns with heart failure) died, 2 after emergency surgery and 1 of intractable heart failure. The remaining 8 patients were managed conservatively and monitored for a mean duration of 3.3 years. Follow-up studies revealed that, of the 22 tumors in these 8 patients, 7 completely regressed, 7 partially regressed, and 8 remained stable. Our results showed no relationship between the tumor location and the regression rate (p = 0.34). CONCLUSIONS: Cardiac rhabdomyoma often presents in TS patients with no major arrhythmia or hemodynamic obstruction. However, in symptomatic neonates with or without TS, cardiac rhabdomyoma is usually fatal. Meticulous prenatal screening and routine echocardiographic examinations of patients with TS can reveal subclinical or clinically occult cardiac rhabdomyomas.