[Efficacy of allogeneic hematopoietic stem cell transplantation based on a total body irradiation conditioning treatment regimen for adult acute lymphocytic leukemia].

Objective: To analyze the efficacy of allo-HSCT with total body irradiation (TBI) and chemotherapy alone in the treatment of adult ALL and to explore the factors affecting prognosis. Methods: The clinical data of 95 adult patients with ALL who underwent allo-HSCT from January 2015 to August 2022 were included. According to the conditioning regimen, the patients were divided into two groups: the TBI plus cyclophosphamide (TBI/Cy) group (n=53) and the busulfan plus cyclophosphamide (Bu/Cy) group (n=42). Hematopoietic reconstitution after transplantation, GVHD, transplantation-related complications, relapse rate (RR), non-relapse mortality (NRM), OS, and LFS were compared, and the factors related to prognosis were analyzed. Results: The median time of neutrophil engraftment was 14 (10-25) days in the TBI/Cy group and 14 (10-24) days in the Bu/Cy group (P=0.106). The median time of megakaryocyte engraftment was 17 (10-42) days in the TBI/Cy group and 19 (11-42) days in the Bu/Cy group (P=0.488). The incidence of grade Ⅱ-Ⅳ acute GVHD (aGVHD) in the TBI/Cy and Bu/Cy groups was 41.5% and 35.7%, respectively (P=0.565). The incidence of grade Ⅲ-Ⅳ aGVHD in these two groups was 24.5% and 4.8%, respectively (P=0.009). The incidence of severe chronic GVHD in the two groups was 16.7% and 13.5%, respectively (P=0.689). The incidence of cytomegalovirus infection, Epstein-Barr virus infection, severe infection, and hemorrhagic cystitis in the two groups was 41.5% and 35.7% (P=0.565), 34.0% and 35.7% (P=0.859), 43.4% and 33.3% (P=0.318), and 20.8% and 50.0% (P=0.003), respectively. The median follow-up time was 37.1 months and 53.3 months in the TBI/Cy and Bu/Cy groups, respectively. The 2-year cumulative RR was 17.0% in the TBI/Cy group and 42.9% in the Bu/Cy group (P=0.017). The 2-year cumulative NRM was 24.5% and 7.1%, respectively (P=0.120). The 2-year LFS was 58.5% and 50.0%, respectively (P=0.466). The 2-year OS rate was 69.8% and 64.3%, respectively (P=0.697). In the multivariate analysis, the conditioning regimen containing TBI was a protective factor for relapse after transplantation (HR=0.304, 95% CI 0.135-0.688, P=0.004), whereas the effect on NRM was not significant (HR=1.393, 95% CI 0.355-5.462, P=0.634). Infection was an independent risk factor for OS after allo-HSCT in adult patients with ALL. Conclusion: allo-HSCT based on TBI conditioning regimen had lower relapse rate and lower incidence of hemorrhagic cystitis for adult ALL, compared with chemotherapy regimen. While the incidence o grade Ⅲ/Ⅳ aGVHD was hgher in TBI conditioning regimen than that in chemotherapy regimen.

Diet changes due to urbanization in South Africa are linked to microbiome and metabolome signatures of Westernization and colorectal cancer.

Transition from traditional high-fiber to Western diets in urbanizing communities of Sub-Saharan Africa is associated with increased risk of non-communicable diseases (NCD), exemplified by colorectal cancer (CRC) risk. To investigate how urbanization gives rise to microbial patterns that may be amenable by dietary intervention, we analyzed diet intake, fecal 16 S bacteriome, virome, and metabolome in a cross-sectional study in healthy rural and urban Xhosa people (South Africa). Urban Xhosa individuals had higher intakes of energy (urban: 3,578 ± 455; rural: 2,185 ± 179 kcal/d), fat and animal protein. This was associated with lower fecal bacteriome diversity and a shift from genera favoring degradation of complex carbohydrates (e.g., Prevotella) to taxa previously shown to be associated with bile acid metabolism and CRC. Urban Xhosa individuals had higher fecal levels of deoxycholic acid, shown to be associated with higher CRC risk, but similar short-chain fatty acid concentrations compared with rural individuals. Fecal virome composition was associated with distinct gut bacterial communities across urbanization, characterized by different dominant host bacteria (urban: Bacteriodota; rural: unassigned taxa) and variable correlation with fecal metabolites and dietary nutrients. Food and skin microbiota samples showed compositional differences along the urbanization gradient. Rural-urban dietary transition in South Africa is linked to major changes in the gut microbiome and metabolome. Further studies are needed to prove cause and identify whether restoration of specific components of the traditional diet will arrest the accelerating rise in NCDs in Sub-Saharan Africa.

Added value of spectral computed tomography quantitative parameters for differentiating tuberculosis-associated fibrosing mediastinitis from endobronchial lung cancer: initial results.

OBJECTIVE: The objective of this study was to explore the added value of spectral computed tomography (CT) parameters to conventional CT features for differentiating tuberculosis-associated fibrosing mediastinitis (TB-associated FM) from endobronchial lung cancer (EBLC). METHODS: Chest spectral CT enhancement images from 109 patients with atelectasis were analyzed retrospectively. These patients were divided into two distinct categories: the TB-associated FM group (n = 77) and the EBLC group (n = 32), based on bronchoscopy and/or pathological findings. The selection of spectrum parameters was optimized with the least absolute shrinkage and selection operator regression analysis. The relationship between the spectrum parameters and conventional parameters was explored using Pearson's correlation. Multivariate logistic regression analysis was used to build spectrum model. The spectrum parameters in the spectrum model were replaced with their corresponding conventional parameters to build the conventional model. Diagnostic performances were evaluated using receiver operating characteristic curve analyses. RESULTS: There was a moderate correlation between the parameters ㏒(L-AEFNIC) - ㏒(L-AEFC) (r= 0.419; p< 0.0001), ㏒(O-AEF40KeV) - ㏒(O-AEFC) (r= 0.475; p< 0.0001), [L-A-hydroxyapatite {HAP}(I)] - (L-U-CT) (r= 0.604; p< 0.0001), {arterial enhancement fraction (AEF) derived from normalized iodine concentration (NIC) of lymph node (L-AEFNIC), AEF derived from CT40KeV of bronchial obstruction (O-AEF40KeV), arterial-phase Hydroxyapatite (Iodine) concentration of lymph node [L-A-HAP(I)], AEF derived from conventional CT (AEFC), unenhanced CT value (U-CT)}. Spectrum model could improve diagnostic performances compared to conventional model (area under curve: 0.965 vs 0.916, p= 0.038). CONCLUSION: There was a moderate correlation between spectrum parameters and conventional parameters. Integrating conventional CT features with spectrum parameters could further improve the ability in differentiating TB-associated FM from EBLC.

COVID-19 vaccines and adverse events of special interest: A multinational Global Vaccine Data Network (GVDN) cohort study of 99 million vaccinated individuals.

BACKGROUND: The Global COVID Vaccine Safety (GCoVS) Project, established in 2021 under the multinational Global Vaccine Data Network™ (GVDN®), facilitates comprehensive assessment of vaccine safety. This study aimed to evaluate the risk of adverse events of special interest (AESI) following COVID-19 vaccination from 10 sites across eight countries. METHODS: Using a common protocol, this observational cohort study compared observed with expected rates of 13 selected AESI across neurological, haematological, and cardiac outcomes. Expected rates were obtained by participating sites using pre-COVID-19 vaccination healthcare data stratified by age and sex. Observed rates were reported from the same healthcare datasets since COVID-19 vaccination program rollout. AESI occurring up to 42 days following vaccination with mRNA (BNT162b2 and mRNA-1273) and adenovirus-vector (ChAdOx1) vaccines were included in the primary analysis. Risks were assessed using observed versus expected (OE) ratios with 95 % confidence intervals. Prioritised potential safety signals were those with lower bound of the 95 % confidence interval (LBCI) greater than 1.5. RESULTS: Participants included 99,068,901 vaccinated individuals. In total, 183,559,462 doses of BNT162b2, 36,178,442 doses of mRNA-1273, and 23,093,399 doses of ChAdOx1 were administered across participating sites in the study period. Risk periods following homologous vaccination schedules contributed 23,168,335 person-years of follow-up. OE ratios with LBCI > 1.5 were observed for Guillain-Barré syndrome (2.49, 95 % CI: 2.15, 2.87) and cerebral venous sinus thrombosis (3.23, 95 % CI: 2.51, 4.09) following the first dose of ChAdOx1 vaccine. Acute disseminated encephalomyelitis showed an OE ratio of 3.78 (95 % CI: 1.52, 7.78) following the first dose of mRNA-1273 vaccine. The OE ratios for myocarditis and pericarditis following BNT162b2, mRNA-1273, and ChAdOx1 were significantly increased with LBCIs > 1.5. CONCLUSION: This multi-country analysis confirmed pre-established safety signals for myocarditis, pericarditis, Guillain-Barré syndrome, and cerebral venous sinus thrombosis. Other potential safety signals that require further investigation were identified.

A comprehensive prognostic analysis of cause-specific mortality in patients with ovarian serous cystadenocarcinoma using a competing-risks model: a case study of the SEER database.

OBJECTIVE: This retrospective study employed a competing-risks analysis utilizing the Surveillance, Epidemiology, and End Results (SEER) database to identify precise prognostic factors associated with ovarian serous cystadenocarcinoma (OSCC) in patients. PATIENTS AND METHODS: Patients with OSCC during 2004-2015 were identified in the SEER database, and their clinicopathological, demographic, and survival data were examined. Univariate analysis using Gray's test and the cumulative incidence function was used to evaluate the prognoses of events of interest. The multivariate analysis involved several models, including the Cox proportional hazards, Fine-Gray, and cause-specific (CS) hazard function models, to estimate the hazard functions of competing risks. Hazard ratios were analyzed to identify the reliability of the prognostic factors. RESULTS: Among the 10,400 individuals diagnosed with OSCC, 5,713 died from the illness, and 1,125 died from other causes. The cumulative incidence rate of events of interest was found to be significant for ethnicity, age at diagnosis, histological grade, American Joint Committee on Cancer (AJCC) stage, chemotherapy and surgery status, tumor size, marital status, and local lymph node metastases (p<0.05). The multivariate analysis revealed that ethnicity, histological grade, surgery and chemotherapy status, age at diagnosis, AJCC stage, marital status, and distant metastases were independent prognostic factors in the Cox model (p<0.05). Finally, the Fine-Gray and CS models demonstrated that ethnicity, histological grade, surgery and chemotherapy status, age at diagnosis, AJCC stage, tumor size, marital status, and combination summary stage were all identified as independent prognostic factors (p<0.05). CONCLUSIONS: This study determined the risk factors for OSCC using a competing risk analysis model established by the SEER database. The findings can help clinicians understand OSCC better and provide more accurate medical support to affected patients.

[Expression of ProEXC and PRMT5 in cervical adenocarcinoma and their clinical significance].

This study observed the expression of ProEXC protein and PRMT5 protein in cervical adenocarcinoma and adjacent tissues, exploring the relationship between the expression of ProEXC and PRMT5 and the auxiliary diagnosis of cervical adenocarcinoma, as well as the clinical pathological parameters. A total of 88 specimens diagnosed with cervical adenocarcinoma from the Second Affiliated Hospital of Soochow University between 2015 and 2020 were collected. Immunohistochemistry was employed to detect the expression of ProEXC and PRMT5 in cervical adenocarcinoma and adjacent tissues, and statistical analysis was conducted. The Cancer Genome Atlas (TCGA) database was utilized to analyze the correlation between the prognosis of cervical adenocarcinoma patients and the expression of ProEXC and PRMT5, as well as their related gene pathways. The GSE39293 dataset from the Gene Expression Omnibus (GEO) was selected to compare the expression levels of ProEXC and PRMT5 in cervical adenocarcinoma cell lines (HELA) before and after antiviral drug treatment.In cervical adenocarcinoma tissues, the expression of ProEXC protein (95.5% vs 4.6%, P<0.001) and PRMT5 protein (81.8% vs 26.1%, P<0.001) was significantly higher than in surrounding adjacent tissues. Their expression was correlated with the tumor's T stage, lymph node metastasis, and human papillomavirus (HPV) infection (P<0.05). TCGA database analysis showed that patients with high expression of MCM2 in PRMT5 and ProEXC had a lower overall survival rate (P<0.05), while the expression of TOP2A was not significantly correlated with survival. In the GSE39293 dataset, the expression of MCM2 (9.34 vs 9.68, P<0.001) and PRMT5 (8.16 vs 8.26, P=0.087) in cells decreased after treatment with cidofovir, while TOP2A (8.54 vs 8.42, P=0.056) expression did not change significantly. In the drug-resistant group, the expression of PRMT5 (8.42 vs 8.16, P=0.002) and MCM2 (9.51 vs 9.34, P=0.029) increased, while TOP2A (8.06 vs 8.54, P<0.001) expression decreased. Gene set enrichment analysis (GSEA) suggested that high expression of ProEXC mainly affected the cell cycle pathway, while high expression of PRMT5 mainly affected the RNA splicing pathway.This study found that ProEXC protein and PRMT5 protein were highly expressed in cervical adenocarcinoma tissues, and the high-expression group had a poorer prognosis, showing a certain correlation with the clinical and pathological characteristics of cervical adenocarcinoma. This may be related to their influence on the cell cycle and RNA synthesis pathways, suggesting their potential significant roles in the progression of cervical adenocarcinoma.

The value of MRI in predicting hepatocellular carcinoma with cytokeratin 19 expression: a systematic review and meta-analysis.

AIM: To evaluate the overall diagnostic performance of magnetic resonance imaging (MRI), different image features, and different image analysis methods in predicting hepatocellular carcinoma (HCC) with cytokeratin 19 (CK19) expression. MATERIALS AND METHODS: A systematic literature search was performed to identify studies using MRI to predict HCC with CK19 expression between 2012 and 2023. Data were extracted to calculate the pooled sensitivity and specificity. Overall diagnostic performance was assessed using areas under the summary receiver operating characteristic curve (AUC). Subgroup analyses were conducted for specific image features and according to image analysis methods (traditional image feature, radiomics, and combined methods). Z-test statistics was used to analyse the differences in diagnostic performance between combined and individual methods. RESULTS: Eleven studies with 14 datasets (1,278 lesions from 1,264 patients) were included. The overall pooled sensitivity, specificity, and AUC with corresponding 95% confidence intervals were estimated to be 0.72 (0.55, 0.85), 0.88 (0.80, 0.93), and 0.89 (0.86, 0.91) for MRI in predicting HCC with CK19 expression. Combined methods had higher sensitivity than image feature methods (0.86 versus 0.54, p=0.001), with no difference in specificity (0.85 versus 0.87, p=0.641). There were no significant differences between radiomics and combined methods regarding sensitivity (p=0.796) and specificity (p=0.535), respectively. CONCLUSION: MRI shows moderate sensitivity and high specificity in identifying HCC with CK19 expression. The application of radiomics can improve the sensitivity of MRI in identifying HCC with CK19 expression.

[Analysis of the serum bile acid profile to facilitate diagnosis and differential diagnosis of NA(+)-taurocholate cotransporting polypeptide deficiency].

Objective: This study focuses on Na(+)-taurocholate cotransporting polypeptide (NTCP) deficiency to analyze and investigate the value of the serum bile acid profile for facilitating the diagnosis and differential diagnosis. Methods: Clinical data of 66 patients with cholestatic liver diseases (CLDs) diagnosed and treated in the Department of Pediatrics of the First Affiliated Hospital of Jinan University from early April 2015 to the end of December 2021 were collected, including 32 cases of NTCP deficiency (16 adults and 16 children), 16 cases of neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD), 8 cases of Alagille syndrome, and 10 cases of biliary atresia. At the same time, adult and pediatric healthy control groups (15 cases each) were established. The serum bile acid components of the study subjects were qualitatively and quantitatively analyzed by ultra-high performance liquid chromatography-tandem mass spectrometry. The data were plotted and compared using statistical SPSS 19.0 and GraphPad Prism 5.0 software. The clinical and bile acid profiles of children with NTCP deficiency and corresponding healthy controls, as well as differences between NTCP deficiency and other CLDs, were compared using statistical methods such as t-tests, Wilcoxon rank sum tests, and Kruskal-Wallis H tests. Results: Compared with the healthy control, the levels of total conjugated bile acids, total primary bile acids, total secondary bile acids, glycocholic acid, taurocholic acid, and glycochenodeoxycholic acid were increased in NTCP deficiency patients (P < 0.05). Compared with adults with NTCP deficiency, the levels of total conjugated bile acids and total primary bile acids were significantly increased in children with NTCP deficiency (P < 0.05). The serum levels of taurochenodeoxycholic acid, glycolithocholate, taurohyocholate, and tauro-α-muricholic acid were significantly increased in children with NTCP deficiency, but the bile acid levels such as glycodeoxycholic acid, glycolithocholate, and lithocholic acid were decreased (P < 0.05). The serum levels of secondary bile acids such as lithocholic acid, deoxycholic acid, and hyodeoxycholic acid were significantly higher in children with NTCP deficiency than those in other CLD groups such as NICCD, Alagille syndrome, and biliary atresia (P < 0.05). Total primary bile acids/total secondary bile acids, total conjugated bile acids/total unconjugated bile acids, taurocholic acid, serum taurodeoxycholic acid, and glycodeoxycholic acid effectively distinguished children with NTCP deficiency from other non-NTCP deficiency CLDs. Conclusion: This study confirms that serum bile acid profile analysis has an important reference value for facilitating the diagnosis and differential diagnosis of NTCP deficiency. Furthermore, it deepens the scientific understanding of the changing characteristics of serum bile acid profiles in patients with CLDs such as NTCP deficiency, provides a metabolomic basis for in-depth understanding of its pathogenesis, and provides clues and ideas for subsequent in-depth research.

Pheochromocytoma in pregnancy: a case report.

BACKGROUND: Pheochromocytoma (PHEO) in pregnancy is a rare disease, and the management of this situation is not well established. The misdiagnosis of the disease often leads to adverse outcomes for both mothers and infants. CASE REPORT: Here, we describe a case of a pregnant woman at 25 weeks' gestation presenting with headache, chest tightness, and shortness of breath, which was found to have a left adrenal mass and hypertensive urgency and diagnosed pregnancy with PHEO in our hospital. The timely diagnosis and proper treatment came with an optimal maternal and fetal outcome. CONCLUSIONS: The case of pheochromocytoma in pregnancy we report demonstrated that early diagnosis and a multidisciplinary approach ensured a favorable prognosis for both maternal and fetal, and we also addressed the importance of individual basis evaluation during the whole journey.

[Analysis of risk factors of radiation-induced toxicity in limited-stage small cell lung cancer treated with hypofractionated intensity-modulated radiotherapy].

Objective: To compare the incidence of radiation-related toxicities between conventional and hypofractionated intensity-modulated radiation therapy (IMRT) for limited-stage small cell lung cancer (SCLC), and to explore the risk factors of hypofractionated radiotherapy-induced toxicities. Methods: Data were retrospectively collected from consecutive limited-stage SCLC patients treated with definitive concurrent chemoradiotherapy in Cancer Hospital of Chinese Academy of Medical Sciences from March 2016 to April 2022. The enrolled patients were divided into two groups according to radiation fractionated regimens. Common Terminology Criteria for Adverse Events (CTCAE, version 5.0) was used to evaluate the grade of radiation esophagus injuries and lung injuries. Logistic regression analyses were used to identify factors associated with radiation-related toxicities in the hypofractionated radiotherapy group. Results: Among 211 enrolled patients, 108 cases underwent conventional IMRT and 103 patients received hypofractionated IMRT. The cumulative incidences of acute esophagitis grade ≥2 [38.9% (42/108) vs 35.0% (36/103), P=0.895] and grade ≥ 3 [1.9% (2/108) vs 5.8% (6/103), P=0.132] were similar between conventional and hypofractionated IMRT group. Late esophagus injuries grade ≥2 occurred in one patient in either group. No differences in the cumulative incidence of acute pneumonitis grade ≥2[12.0% (13/108) vs 5.8% (6/103), P=0.172] and late lung injuries grade ≥2[5.6% (6/108) vs 10.7% (11/103), P=0.277] were observed. There was no grade ≥3 lung injuries occurred in either group. Using multiple regression analysis, mean esophageal dose ≥13 Gy (OR=3.33, 95% CI: 1.23-9.01, P=0.018) and the overlapping volume between planning target volume (PTV) and esophageal ≥8 cm(3)(OR=3.99, 95% CI: 1.24-12.79, P=0.020) were identified as the independent risk factors associated with acute esophagitis grade ≥2 in the hypofractionated radiotherapy group. Acute pneumonitis grade ≥2 was correlated with presence of chronic obstructive pulmonary disease (COPD, P=0.025). Late lung injuries grade ≥2 was correlated with tumor location(P=0.036). Conclusions: Hypofractionated IMRT are tolerated with manageable toxicities for limited-stage SCLC patients treated with IMRT. Mean esophageal dose and the overlapping volume between PTV and esophageal are independently predictive factors of acute esophagitis grade ≥2, and COPD and tumor location are valuable factors of lung injuries for limited-stage SCLC patients receiving hyofractionated radiotherapy. Prospective studies are needed to confirm these results.

[Clinicopathological and gene mutation characteristics of uterine carcinosarcoma].

To explore the clinicopathological characteristics, immunophenotype, diagnosis and differential diagnosis of uterine carcinosarcoma (UCS), and to explore the gene mutation characteristics and tumor mutation burden (TMB) of UCS. The clinical imaging, pathomorphological data and immunohistochemical expression of 4 cases of UCS, which were archived in the Department of Pathology of the Second Affiliated Hospital of Soochow University from January 2021 to May 2022 were retrospectively analyzed. All exon groups of 4 cases of UCS were sequenced. All the 4 patients were female, aged 47-81 years. The maximum diameter of the tumor was 4.0-13.0 cm, and the boundary was unclear. Microscopically, the tumor was composed of malignant epithelium and sarcoma. Immunohistochemistry showed that the epithelial components of 4 patients expressed broad-spectrum cytokeratin (AE1/E3), the sarcoma components expressed Vimentin, PAX8, ER, PR were expressed to varying degrees, and Ki-67 positive index was high (60%-90%). There were 3 p53 missense mutations, 1 nonsense mutation, 4 MLH1, PMS2, MSH2, MSH6 were positive and PD-L1 was negative. The sequencing results of the whole exon group of 4 UCS patients showed that TP53, BCL9L, BRD4, CLTCLI, PSMD1I, PLEC genes showed a high mutation ratio, which was 3/4, 2/4, 2/4, 2/4, 2/4, 2/4, respectively. TMB analysis showed that the TMB of 4 cases of UCS was<5 mut/Mb. UCS is a rare and highly malignant endometrial tumor. The sequencing results of the whole exon group suggested that TP53, BCL9L, BRD4 and other genes had high mutation rates, suggesting that the occurrence and development of UCS may be closely related to Wnt signaling pathway. Molecular typing indicated that 3 cases of UCS were of high copy number type/p53 mutation type, and 1 case had POLD1 mutation. Microsatellite stability, low PD-L1 expression and TMB results suggested that UCS patients have no obvious advantage in immunotherapy.

[Determination of six benzene homologues in human blood by purge and trap-gas chromatography-mass spectrometry].

Objective: To establish a purge and trap-gas chromatography-mass spectrometry method based on soil analysis model for the determination of six benzene homologues (benzene, toluene, ethylbenzene, m-xylene, p-xylene and o-xylene) in human blood. Methods: From September 2020 to May 2021, diatomite was used as a dispersant to add 2.0 ml blood sample and fully mixed. The sample was directly injected into the purging and collecting bottle after purging. The gas chromatography column was used for separation. The retention time locking was used for qualitative analysis and the selected ion scanning mode (SIM) was used for detection. The detection limit and recovery rate of the method were analyzed. Results: The linear range of the method for the determination of six benzene homologues in human blood was 0.02-10.00 ng/ml, the correlation coefficient was 0.9927-0.9968, the detection limit was 0.006-0.016 ng/ml, the recovery rate of sample spiking was 84.39%-102.41%, and the precision of the method was 3.06%-6.90%. Conclusion: Purge and trap-gas chromatography-mass spectrometry can simultaneously determine the contents of six benzene homologues in human blood. The pretreatment method is simple, time-saving, and the method has low detection limit, which provides a scientific basis for the detection of benzene homologues in human body.

Association between the Lymphocyte-to-C-Reactive Protein Ratio and Survival Outcomes in Cancer Patients with GLIM-Defined Malnutrition: A Multicenter Study.

BACKGROUND AND AIMS: This study assessed the prognostic value of LCR in patients with cancer-associated malnutrition (CAM). Systemic inflammatory markers, particularly the lymphocyte-to-C-reactive protein ratio (LCR), are related to the survival of patients with CAM. The present retrospective analysis based on a prospective multicenter cohort study, which involved 1,437 hospitalized patients with CAM. METHODS: The area under the receiver operating characteristic curve (AUC) of ten inflammatory indicators-LCR, advanced lung cancer inflammation index, neutrophil-to-lymphocyte ratio, prognostic nutritional index, modified Glasgow prognostic score, systemic immune-inflammation index, albumin-to-globulin ratio, LCR score, glucose-to-lymphocyte ratio, and platelet-to-lymphocyte ratio-were constructed. Nutritional status, blood markers, and quality of life (QoL) were evaluated within 48 h of admission. The overall survival (OS) was evaluated from September 1 to December 29, 2021. RESULTS: A total of 1,431 cancer patients diagnosed with malnutrition based on the Global Leadership Initiative on Malnutrition (GLIM) criteria. Male patients were 62.8% of all, and the mean age was 60.66 years old. The AUC of LCR was higher than that of other inflammatory markers. The restricted cubic spline (RCS) of the Hazard ratios (HRs) showed an inverse L-shaped relationship with LCR. In addition, patients with low LCR had significantly poorer OS than those with high LCR. The addition of LCR to the model increased the predictive ability of 1-year mortality (AUC increase of 0.036), 3-year mortality (AUC increase of 0.038), and 5-year mortality (AUC increase of 0.031). CONCLUSIONS: Assessing the LCR can help the medical staff identify cancer patients with nutritional deficiency at high risk of oncological outcomes and develop individualized therapeutic strategies.

[Spectral CT multi-parameter imaging in preoperatively evaluation the status of lymphovascular and perineural invasion of gastric cancer].

Objective: To explore the application value of spectral CT multi-parameter imaging in preoperative assessment the status of lymphovascular invasion (LVI) and perineural invasion (PNI) in patients with gastric cancer. Methods: A total of 62 patients who underwent energy spectral CT and with pathology confirmed gastric cancer in Lanzhou Uiversity Second Hospital from September 2020 to September 2021 were retrospectively collected, which including 46 males and 16 females, aged from 36 to 71 (57.5±9.1) years. According to the presence or absence of LVI/PNI in postoperative pathological results, they were divided into the positive group (42 cases) and the negative group (20 cases). The CT values of 40 keV and 70 keV (CT40 keV, CT70 keV), iodine concentration (IC), normalized iodine concentration (NIC) were measured in the arterial phase, the venous phase, and the delay phase, and the spectral curve slope of 40 keV to 70 keV (K(40-70)) and the combined parameters (the arterial phase: AP~all, the venous phase: VP~all, the delay phase: DP~all) were calculated. Spectral parameters between the positive and negative groups were compared, and the receiver operating characteristic curve (ROC) with the area under the curve (AUC), sensitivity, specificity, and optimal threshold were calculated for evaluating the diagnostic performance of each parameter. Results: The CT40 keV, CT70 keV, K(40-70), IC, and NIC in the arterial phase and the venous phase and the CT70 keV and NIC in the delay phase of the LVI/PNI-positive group were all higher than those of the negative group [the representative parameters: the arterial phase NIC 0.14±0.04 vs 0.12±0.04, the venous phase NIC 0.5(0.5, 0.6) vs 0.4(0.4, 0.5), the delay phase NIC 0.6±0.1 vs 0.5±0.1, all P<0.05]. ROC curve analysis showed that the diagnostic efficacy of the parameters of the venous phase is better than that of the arterial phase and the delay phase, and the diagnostic efficiency of the combined parameters is better than that of the individual parameters. The AUC value, sensitivity, and specificity of the most optimal parameter VP~all of the venous phase were 0.931(95%CI:0.872-0.990), 80.95%, and 95.00%, respectively. Conclusions: In the preoperative evaluation the status of the LVI and PNI in gastric cancer, the diagnostic efficacy in the venous phase parameters is better than that in the arterial phase and delay phase, and the diagnostic efficacy of combined parameters is better than that of individual parameters.

Does prior failed shock-wave lithotripsy impact outcomes of ureterorenoscopy? A systematic review and meta-analysis.

OBJECTIVE: The study aimed to compare the outcomes of patients undergoing ureterorenoscopy (URS) after failed shock-wave lithotripsy (SWL) (Salvage URS) with those undergoing URS without any history of SWL (Primary URS). MATERIALS AND METHODS: PubMed, Embase, and CENTRAL databases were searched up to 10th January 2021 for studies comparing outcomes of salvage URS vs. primary URS. Odds ratios (OR) with 95% confidence intervals (CI) were calculated for procedure success and complications. Operating time was summarized using mean difference (MD). RESULTS: Seven retrospective studies were included. Meta-analysis indicated no statistically significant difference in the success rates of URS between the salvage URS and primary URS groups (OR: 0.83 95% CI: 0.65, 1.06 I2=0% p=0.13). On subgroup analysis, the success rate was significantly reduced in the salvage URS group for renal stones (OR: 0.55 95% CI: 0.34, 0.91 I2=0% p=0.02) but with no difference for ureter stones OR: 0.90 95% CI: 0.67, 1.21 I2=0% p=0.49). Pooled analysis demonstrated a tendency of longer operating time in the salvage URS group as compared to the primary URS group, albeit with a statistically non-significant difference (MD: 8.91 95% CI: -0.56, 18.38 I2=98% p=0.07). Meta-analysis indicated significantly increased complications in the salvage URS group as compared to the primary URS group (OR: 1.83 95% CI: 1.34, 2.49 I2=0% p=0.0001). CONCLUSIONS: Evidence from retrospective studies suggests that patients undergoing salvage URS for renal stones have significantly lower success rates which is not the case for ureteral stones. There is a non-significant tendency of increased operating times for salvage URS. Complication rates are significantly higher for salvage URS as compared to primary URS. Future studies with propensity-score matching are required to strengthen current conclusions.

[Establishment and application of a nomogram model for prognostic risk prediction in patients with epithelial ovarian cancer].

Objective: To explore the prognostic factors of epithelial ovarian carcinoma (EOC), construct a nomogram model, and evaluate the prognosis of EOC patients. Methods: A retrospective analysis was performed on clinicopathological data of 208 cases of EOC patients who received initial treatment in the First Affiliated Hospital of Army Medical University from August 11, 2016 to July 11, 2018, including age, preoperative ascites, preoperative neoadjuvant chemotherapy, surgical method, pathological type, pathological differentiation degree, surgical pathology stage, preoperative and post-chemotherapy serum cancer antigen 125 (CA125) level, human epididymal protein 4 (HE4) level, platelet count and platelet/lymphocyte number ratio (PLR). The univariate and multivariate Cox risk ratio models were used to analyze the related factors affecting progression free survival (PFS) in EOC patients, and the prediction nomogram of PFS in EOC patients was established to evaluate its efficacy in predicting PFS. Results: Univariate analysis showed that preoperative neoadjuvant chemotherapy, pathological type, pathological differentiation degree, surgical pathology stage, serum CA125 and HE4 level before operation and after chemotherapy, platelet count and PLR before operation and after chemotherapy were significantly correlated with PFS in EOC patients (all P<0.05). Multivariate analysis showed that surgical pathology stage, preoperative PLR, serum CA125 and HE4 level after chemotherapy were independent prognostic factors affecting PFS of EOC patients (all P<0.01). The index coefficient of the prediction model for the prognosis of EOC patients established by this method was 0.749 (95% CI: 0.699-0.798), which had good prediction ability, and could help clinicians to more accurately evaluate the prognosis of EOC patients. Conclusion: The nomogram model constructed based on surgical pathology stage, preoperative PLR, serum CA125 and HE4 level after chemotherapy could effectively predict the PFS of EOC patients after initial treatment, could help clinicians to screen high-risk patients, provide individualized treatment, and improve the prognosis of EOC patients.

A non-coding RNA balancing act: miR-346-induced DNA damage is limited by the long non-coding RNA NORAD in prostate cancer.

BACKGROUND: miR-346 was identified as an activator of Androgen Receptor (AR) signalling that associates with DNA damage response (DDR)-linked transcripts in prostate cancer (PC). We sought to delineate the impact of miR-346 on DNA damage, and its potential as a therapeutic agent. METHODS: RNA-IP, RNA-seq, RNA-ISH, DNA fibre assays, in vivo xenograft studies and bioinformatics approaches were used alongside a novel method for amplification-free, single nucleotide-resolution genome-wide mapping of DNA breaks (INDUCE-seq). RESULTS: miR-346 induces rapid and extensive DNA damage in PC cells - the first report of microRNA-induced DNA damage. Mechanistically, this is achieved through transcriptional hyperactivation, R-loop formation and replication stress, leading to checkpoint activation and cell cycle arrest. miR-346 also interacts with genome-protective lncRNA NORAD to disrupt its interaction with PUM2, leading to PUM2 stabilisation and its increased turnover of DNA damage response (DDR) transcripts. Confirming clinical relevance, NORAD expression and activity strongly correlate with poor PC clinical outcomes and increased DDR in biopsy RNA-seq studies. In contrast, miR-346 is associated with improved PC survival. INDUCE-seq reveals that miR-346-induced DSBs occur preferentially at binding sites of the most highly-transcriptionally active transcription factors in PC cells, including c-Myc, FOXA1, HOXB13, NKX3.1, and importantly, AR, resulting in target transcript downregulation. Further, RNA-seq reveals widespread miR-346 and shNORAD dysregulation of DNA damage, replication and cell cycle processes. NORAD drives target-directed miR decay (TDMD) of miR-346 as a novel genome protection mechanism: NORAD silencing increases mature miR-346 levels by several thousand-fold, and WT but not TDMD-mutant NORAD rescues miR-346-induced DNA damage. Importantly, miR-346 sensitises PC cells to DNA-damaging drugs including PARP inhibitor and chemotherapy, and induces tumour regression as a monotherapy in vivo, indicating that targeting miR-346:NORAD balance is a valid therapeutic strategy. CONCLUSIONS: A balancing act between miR-346 and NORAD regulates DNA damage and repair in PC. miR-346 may be particularly effective as a therapeutic in the context of decreased NORAD observed in advanced PC, and in transcriptionally-hyperactive cancer cells.

[Differentiation between hyperintense hepatocellular carcinoma and focal nodular hyperplasia in hepatobiliary phase with multimodal parameters of magnetic resonance imaging].

Objective: To differentiate hyperintense hepatocellular carcinoma (HCC) with focal nodular hyperplasia (FNH) in the hepatobiliary phase by MRI multimodal parameters. Methods: A retrospective cross-sectional study method was adopted. Clinical data on 15 cases with hyperintense HCC and 15 cases with FNH in the hepatobiliary phase admitted to the First Affiliated Hospital of the Army Medical University from January 2012 to December 2019 were collected. All patients with solitary lesions who underwent Gd-EOB-DTPA-enhanced MRI examinations were included. Surgically resected specimens were verified by pathological and immunohistochemical examination. HCC and FNH imaging features were analyzed by two radiologists. Results: (1) HCC and FNH apparent diffusion coefficient (ADC) values were 1 205.07±239.65×10-3 mm2/s and 1 434.73±217.6×10-3 mm2/s, respectively, and the SIADC difference was statistically significant (P<0.05) between the two groups. (2) In the dynamic contrast-enhanced MRI sequence, 15 cases of HCC were significantly enhanced in the arterial phase, of which 13 cases were characterized by continuous enhancement, and 2 cases were characterized by wash-in and wash-out enhancement. There was no statistically significant difference (P>0.05) between the two groups. SIenhancement rate between HCC and FNH (1.39±0.60 vs. 1.33±0.50, P>0.05) had no significant difference. (3) HCC and FNH morphological features in the hepatobiliary phase included: annular hypointensity: HCC (8 cases) vs. FNH (0 cases); contrast filling defects: HCC (8 cases) vs. FNH (0 cases); linear hyposignal separation: HCC (10 cases) vs. FNH (0 cases); and stellate scars: HCC (0) vs. FNH (5 cases), and there were statistically significant differences (P<0.05) between the two groups . Conclusion: Multimodal MRI have significant value for differentiating hyperintense HCC and FNH in the hepatobiliary phase.