Regulation of Immune Balance by Traditional Chinese Medicine in Treatment of Cough Variant Asthma： A Review / 中国实验方剂学杂志

Cough variant asthma （CVA） is a chronic respiratory disease with cough as its main symptom. The occurrence of CVA is closely related to non-specific airway inflammation， and its pathogenesis involves environmental， genetic， immune， and other factors. In recent years， the advantages of traditional Chinese medicine （TCM） in the treatment of CVA have attracted the attention of experts and scholars in China and abroad， especially its prominent role in regulating immune balance， relieving cough symptoms in CVA patients， and reducing recurrence. T Helper cells 1 （Th1）， T helper cells 2 （Th2）， T helper cells 17 （Th17）， and regulatory T cells （Treg） are derived from CD4+ T cells. Immune imbalance of Th1/Th2 and Th17/Treg is a new hotspot in the pathogenesis of CVA and a potential key target in the treatment of CVA by TCM. Th cell subsets are in dynamic balance under physiological conditions， maintaining respiratory immune homeostasis in which pro-inflammatory cytokines and anti-inflammatory cytokines are balanced. Immature helper T cells （Th0） can be differentiated into Th1， Th2， Th17， Treg， and other cell subsets due to cytokine types in the microenvironment in the stage of CVA maturation. The proliferation of Th2 cells leads to eosinophilic airway inflammation. Excessive differentiation of Th17 cells induces neutrophil airway inflammation. Th1/Th2 and Th17/Treg cells are mutually restricted in number and function， and the immune imbalance of Th1/Th2 and Th17/Treg is easy to aggravate the generation of inflammatory response. Restoring immune balance is particularly important for the airway anti-inflammatory therapy of CVA. In this paper， the imbalance of Th1/Th2 and Th17/Treg and the pathogenesis of CVA were systematically expounded. Meanwhile， the latest research on the regulation of immune imbalance by TCM compound， single TCM， and its effective ingredients in the treatment of CVA was reviewed. It provides ideas and references for revealing the scientific connotation of TCM regulating immune balance therapy of CVA， as well as the development of clinical treatment and basic research of CVA.

Insulin-like growth factor binding protein 3 promoter variant (rs2854744) is associated with nonalcoholic fatty liver disease

ABSTRACT Objective: Nonalcoholic fatty liver disease (NAFLD) is a chronic liver disease and a growing global epidemic. In NAFLD, liver fat surpasses 5% of hepatocytes without the secondary causes of lipid accumulation or excessive alcohol consumption. Given the link between NAFLD and insulin resistance, the possible association between the rs2854744 (−202 G>T) promoter polymorphism of insulin-like growth factor binding protein 3 (IGFBP3) gene and NAFLD was investigated in this study. Materials and methods: In this genetic case-control association study, the IGFBP3 rs2854744 genotypes of 315 unrelated individuals, including 156 patients with biopsy-proven NAFLD and 159 controls, were determined using polymerase chain reaction/restriction fragment length polymorphism analyses. Results: The "GT+TT" genotype of the IGFBP3 rs2854744 polymorphism, compared with the "GG" genotype, was associated with a 2.7-fold increased risk of NAFLD after adjustment for confounding factors (P = 0.009; odds ratio [OR] = 2.71; 95% confidence interval [CI] = 1.19-3.18). Additionally, the IGFBP3 rs2854744 "T" allele, in comparison with the "G" allele, was significantly overrepresented in NAFLD patients than the controls (P = 0.008; OR = 1.85; 95%CI = 1.23-2.94). Conclusion: Our findings first indicated that the IGFBP3 rs2854744 "GT+TT" genotype is a marker of increased NAFLD susceptibility; however, it needs to be supported by further investigations in other populations.

Comparative analysis of SARS-CoV-2 variants Alpha (B.1.1.7), Gamma (P.1), Zeta (P.2) and Delta (B.1.617.2) in Vero-E6 cells: ultrastructural characterization of cytopathology and replication kinetics

Abstract This study compares the effects of virus-cell interactions among SARS-CoV-2 variants of concern (VOCs) isolated in Brazil in 2021, hypothesizing a correlation between cellular alterations and mortality and between viral load and transmissibility. For this purpose, reference isolates of Alpha, Gamma, Zeta, and Delta variants were inoculated into monolayers of Vero-E6 cells. Viral RNA was quantified in cell supernatants by RT‒PCR, and infected cells were analyzed by Transmission Electron Microscopy (TEM) for qualitative and quantitative evaluation of cellular changes 24, 48, and 72 hours postinfection (hpi). Ultrastructural analyses showed that all variants of SARS-CoV-2 altered the structure and function of mitochondria, nucleus, and rough endoplasmic reticulum of cells. Monolayers infected with the Delta variant showed the highest number of modified cells and the greatest statistically significant differences compared to those of other variants. Viral particles were observed in the cytosol and the cell membrane in 100 % of the cells at 48 hpi. Alpha showed the highest mean particle diameter (79 nm), and Gamma and Delta were the smallest (75 nm). Alpha and Gamma had the highest particle frequency per field at 48 hpi, while the same was observed for Zeta and Delta at 72 hpi and 24 hpi, respectively. The cycle threshold of viral RNA varied among the target protein, VOC, and time of infection. The findings presented here demonstrate that all four VOCs evaluated caused ultrastructural changes in Vero-E6 cells, which were more prominent when infection occured with the Delta variant.

La genética de la epilepsia en la práctica clínica / The genetics of epilepsy in the clinical practice

Resumen La epilepsia es un trastorno neurológico caracterizado por crisis epilépticas recurrentes no provocadas, en el cual la genética tiene un factor etiológico importante. Durante las últimas décadas se ha logrado encontrar genes específicos involucrados en la patogénesis de esta condición. Actualmente existen múltiples exámenes disponibles en la práctica clínica para el diagnóstico genético, siendo los más útiles los paneles multi-genes y la secuenciación del exoma completo por medio de next generation sequencing (NGS). El tener un diagnósti co genético puede mejorar la calidad de vida de cada paciente y su familia, al mismo tiempo que nos ayuda a individualizar el tratamiento haciéndolo más eficaz. Algunos ejemplos en los que el diagnóstico genético puede modificar la conducta terapéutica incluyen el gen SCN1A en que se recomienda no utilizar medicamentos bloqueadores de canales de sodio y el gen SLC2A1 en el que se recomienda el inicio de la dieta cetogénica. El futuro de la investigación en medicina de precisión en epilepsia es muy prometedor, con el objetivo de que cada paciente reciba un tratamiento acorde a su etio logía genética.

Abstract Epilepsy is a neurological disorder characterized by recurrent unprovoked seizures. It is known that genetics play an important etiology roll. During the last decades it has been possible to find specific genes involved in the pathogenesis of this condition. There are currently multiple studies available in clinical practice for genetic diagnosis, the most useful being the next generation se quencing (NGS) techniques with multi-gene panels and whole exome sequencing. Having a genetic diagnosis can help improve the quality of life of each patient and their family, while it helps us to individualize the treatment, making it more effective. Some examples in which ge netic diagnosis can modify therapeutic conduct include the SCN1A gene, in which it is recommended not to use drugs that block Sodium channels, and the SLC2A1 gene, in which starting ketogenic diet is recommended. The future of precision medicine research in epilepsy is very promising, with the goal that each patient receives treatment according to their genetic etiology.

The rhabdoid variant of adrenocortical carcinoma-Report of three cases and literature review

Adrenocortical carcinoma (ACC) is a rare and aggressive malignancy. Extensive rhabdoid morphology in ACC has been described recently in very few cases. The proportion of rhabdoid morphology and the role of SMARCB1/ INI1 expression in these tumor cells to diagnose the specific variant is not described in the literature. We reviewed the clinicopathological features of nine cases of adrenocortical neoplasm. Out of which, three cases of ACC showed predominant rhabdoid morphology. Large discohesive cells with abundant cytoplasm containing eosinophilic inclusions, eccentric vesicular nucleus, and prominent nucleoli. INI1 immunostain was retained in all cases. We reported the rhabdoid variant of ACC, a novel entity, and its diagnostic approach from their histological mimickers. Identifying more cases of this entity will help to clearly understand the pathogenesis, biologic behaviour, and any specific molecular alterations in the future.

Identification of rare atypical BCR-ABL1 transcript: A case report

CML is characterized by the presence of a BCR-ABL1 fusion transcript. Several guidelines have been published for its detection and molecular monitoring. Here, a case is described of chronic myeloid leukemia presenting in the blast phase with a rare variant transcript, with a discussion on possible red flags in its detection and genetic testing and description of the patient's clinical characteristics. This case highlights the pitfalls of using real-time quantitative reverse-transcription polymerase chain reaction (RQ-PCR) for diagnosis of CML, especially when the clinical picture and the test results are discordant.

The B-cell non-Hodgkin’s lymphoma: An enigma to diagnose

Non-Hodgkin’s lymphoma is a heterogeneous group of malignancies characterized by an abnormal clonal proliferation of T-cells, B-cells, or both. Sometimes, tuberculosis and lymphoma presentation can share common symptoms and features. In this case report, we present the case of a 28-year-old female patient who came with a chief complaint of swelling on the right side of the face for the past 6 months. Initially, it was not associated with pain but gradually developed severe pain over the region and reduced salivary flow. The patient was planned for surgery with a differential diagnosis of salivary gland pathology. Post-operatively, the histopathological report showed atypical cells which were diffusely positive for cluster of differentiation (CD)20. Focally positive for CD45 and CD3 which was positive in reactive T lymphocytes. Immunohistochemistry pattern favors the diagnosis of B-cell type NHL. Through this case report, we want to share our experience in treating an aggressive tumor that mimics salivary gland pathology.

Ayudas diagnósticas y diagnóstico diferencial de la enfermedad de Pompe / Diagnostic aids and differential diagnosis of Pompe disease

Introducción: La enfermedad de Pompe (EP) o glucogenosis tipo II es una enfermedad autosómica recesiva causada por mutaciones en el gen GAA que codifica para la proteína alfa-1,4-glucosidasa. Su deficiencia lleva a un almacenamiento anormal de glucógeno en los lisosomas de varias células, a través de los diferentes tejidos, lo que causa un compromiso musculoesquelético predominante. Contenidos: Los fenotipos de la enfermedad dependen de las variantes genéticas y de los niveles de la actividad enzimática residual. La enfermedad se presenta como EP de inicio infantil, EP de inicio tardío y EP intermedio, por lo que es de suma importancia su diagnóstico temprano, por medio de estudios moleculares como la secuenciación de Sanger y la secuenciación de nueva generación. Conclusiones: Se ha demostrado, mediante diferentes estudios, que las variaciones genéticas pueden diferir entre etnias, y es importante su caracterización molecular para determinar el tratamiento más adecuado, de acuerdo con el estado del material inmunológico de reacción cruzada (CRIM).

Introduction: Pompe disease (PD) or Glycogenosis Type II is a rare autosomal recessive disease caused by mutations in the GAA gene that codes for the alpha-1,4-glucosidase protein. Its deficiency leads to abnormal glycogen storage in the lysosomes of various cells throughout the different tissues causing a predominant musculoskeletal compromise. Contents: The phenotypes of the disease depend on the genetic variants and the levels of residual enzyme activity, presenting as infantile-onset PD, late-onset PD, and intermediate PD; Therefore, early diagnosis of the disease through molecular studies such as Sanger sequencing and new generation sequencing is of utmost importance. Conclusions: It has been shown through different studies that genetic variations can vary between ethnic groups and the molecular characterization of the variants is important to determine the most appropriate treatment depending on the state of the cross-reactive immunological material (CRIM)

Introducción al filtrado, análisis y curación de variantes genéticas en pacientes con Discapacidad Intelectual / Introduction to filtering, analysis and curation of genetic variants in patients with Intellectual Disability

Resumen Actualmente la secuenciación del exoma completo (WES; Whole-exome sequencing) mediante la técnica NGS (Next-generation sequencing) es uno de los estudios genéticos más solicitados dentro del abordaje de pacientes con Discapacidad Intelectual con o sin otras anomalías. Al igual que con otros proce dimientos y estudios clínicos, es conveniente que los médicos prescriptores tengan una comprensión clara de los alcances y limitaciones del uso de WES, del proceso de análisis de las variantes genéticas identificadas, así como de aspectos a evaluar acerca de la calidad y estructura de los informes de los estudios de NGS, con el objetivo de que puedan interpretar mejor los resultados de un estudio y plantear de la mejor manera la correlación de los mismos con la clínica observada.

Abstract Currently, Whole exome sequencing (WES) using NGS (Next-generation sequencing) technology is one of the most requested genetic studies within the approach of patients with intellectual disability with or without other anomalies. As with other procedures and clinical studies, it is convenient for prescribing physicians to have a clear understanding of the scope and limitations of the use of WES, the analysis process of the genetic variants identified, as well as aspects to be evaluated regarding quality and structure of the reports of the NGS studies, with the aim that they can better interpret the results of a study, evaluate its quality, and propose in the best way the correlation of the same with the observed phenotype.

Biphasic squamoid alveolar renal cell carcinoma: A rare entity with an even rarer presentation as cutaneous metastases – A case report

Biphasic squamoid alveolar renal cell carcinoma (BSARCC) is a newly emerging distinct and rare morphologic variant of renal cell carcinoma (RCC). Morphological, immunohistochemical, and molecular data have shown that BSARCC is closely related to papillary RCC type 1. We report a case of Biphasic squamoid alveolar renal cell carcinoma with a rare presentation as cutaneous metastases. This variant tends to show an aggressive behavior. Hence, accurate histopathological diagnosis can help in effective treatment and for close follow-up of the patients.

A comparative computational approach on the most deleterious missense variant in Connexin 43 protein and its potent inhibitor analysis

Intercellular communication between the cell plays an essential role in cell growth and cell formation, including migration, metabolism, and cell differentiation. Cell function and tissue homeostasis are maintained through gap junction intercellular communication (GJIC), thus regulating connexin hemichannels. Mis regulation of such connexin, especially connexin (Cx) 43, affects a comprehensive process, including cell differentiation, inflammation, and cell death. Mis regulation may be due to the missense variant in Cx43. Thus, we screened the complete set of mutations from public mutational databases and obtained 219 missense variants, which were then classified based on their pathogenicity, functional impact, stability, conservation, and physiochemical properties. Variant L214P was scrutinized to have the most deleterious, which was then modelled using the I-TASSER server and performed molecular docking analysis to screen potent inhibitors. The compound Kanamycin, Ginsenoside, and Astragaloside IV have better interactions with Cx43 mutant with a maximum of 5 hydrogen bonds. Ginsenoside is a compound that follows a Lipinski rule of five. Thus, the result obtained from this study suggests that Ginsenoside would be a better potent inhibitor for native and mutant Cx43.

A bolt from the blue in a testicular mass - continuous Splenogonadal fusion with maturation arrest

ABSTRACT Splenogonadal fusion is an infrequent cause of testicular or scrotal swelling with less than 250 cases reported. We report the case of a 27-year-old male who presented with painless scrotal swelling. The sonography showed a homogeneous, well-encapsulated left extratesticular mass, which was surgically removed. The gross examination revealed a grey-brown tissue below the left testis. The microscopy of the grey-brown mass revealed splenic tissue, and the testis showed maturation arrest, resulting in the diagnosis of splenogonadal fusion. These can be easily mistaken for a tumor, especially in this age group. Reporting such an entity increases awareness among clinicians, radiologists and pathologists, which will aid in preventing an orchiectomy for these patients.

Frequency of F508del Variant in Patients with Cystic Fibrosis from Paraguay

Abstract Cystic fibrosis (CF) is an autosomal recessive disorder and is caused by variants in the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) gene. We aimed to study the frequency of the F508del variant, the most common variant worldwide, in patients with CF from Paraguay. The frequency of the F508del variant in Paraguayan patients with a clinical diagnosis of CF was assessed using a polymerase chain reaction followed by the sequencing of the PCR products. 43 of the 86 patients (50%) were homozygous for the F508del variant, 28 were heterozygous (32.56%), and the remaining 15 (17.44%) were non-carriers. In terms of alleles, there were 114 mutated (114/172 or 66.28%) and 58 did not correspond to this variant (58/172 or 33.72%). This is the first study of the frequency of the F508del variant in patients with CF in Paraguay. This information is of utmost relevance when planning and offering treatments from health services.

Clinical characteristics of family clustering pediatric and adult cases with severe acute respiratory syndrome coronavirus 2 Omicron variant infection / 中华传染病杂志

Objective:To investigate the clinical characteristics of family clustering pediatric and adult cases with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant infection in Shanghai City.Methods:A field investigation among the pediatric cases with Omicron variant infection and their household contacts from April 4 to April 30, 2022 in Children′s Hospital of Fudan University was conducted. The informations on case finding, clinical manifestations and SARS-CoV-2 vaccination status were collected. The epidemiological and clinical characteristics were compared between pediatric cases and adult cases. The independent sample t test or chi-square test was used for statistical analysis, and the relative risk ( RR) and 95% confidence interval (95% CI) were used to evaluate the protective effect of vaccination on the infection of Omicron variant. Results:There were 1 274 family members in 297 families including 370 children and 904 adults of whom 1 110(87.13%) were infected with Omicron variant, with 989(89.10%) symptomatic and 121(10.90%) asymptomatic. There were 355 children infected with Omicron variant, of whom 337(94.93%) were symptomatic, and the main manifestations were fever (96.74%(326/337)) and cough (40.36%(136/337)). Only one pediatric case with Rett syndrome developed critically severe pneumonia. A total of 194 pediatric cases had imaging examination, 64(32.99%) showed pulmonary inflammatory lesions. There were 755 adult cases infected with Omicron variant, of whom 652(86.26%) reported symptoms, and the main manifestations were fever (73.16%(477/652)) and cough (49.85%(325/652)). Among symptomatic cases, fever was more common in pediatric cases than in adult cases, while cough was more common in adult cases than in pediatric cases, and the differences were both statistically significant ( χ2=80.87 and 8.04, respectively, both P<0.01). The fever spike was higher in pediatric cases than in adult cases ((39.3±0.7) ℃ vs (38.6±0.6) ℃), and the difference was statistically significant ( t=9.85, P<0.001). The interval from the onset of symptoms to cycle threshold (Ct) value of the nucleic acid of Omicron variant≥35 was longer in pediatric cases than in adult cases ((13.0±3.1) d vs (10.9±3.6) d), and the difference had statistically significance ( t=2.97, P=0.004). Among 160 children aged 3 to 18 years, 54 (33.75%) received two-dose vaccination. Among the 904 adults, 388 (42.92%) received two-dose vaccination and 293 (32.41%) received a booster dose. In the adult cases, the risk of symptomatic infection was reduced by only 8% ( RR=0.92, 95% CI 0.86 to 0.98, P=0.014) following two-dose vaccination, and the risks of fever and cough following booster vaccination were reduced by 42%( RR=0.58, 95% CI 0.49 to 0.67, P=0.001) and 50% ( RR=0.50, 95% CI 0.34 to 0.78, P=0.001), respectively. Conclusions:Secondary attack rate and symptomatic rate of household infection are high in the context of the Omicron variant outbreak in Shanghai. Symptomatic infection is common in children and adults in household setting. Fever is the most common symptom and fever duration is short. Booster vaccination may provide certain protection against common symptoms caused by Omicron variant infection.

COVID-19 surveillance via wastewater:Introduction of wastewater-based epidemiology / 西安交通大学学报(医学版)

Since the outbreak of the COVID-19 global pandemic in 2019, monitoring COVID-19 infection status and trend through wastewater, known as wastewater-based epidemiology (WBE), has been widely used in many countries and regions. WBE consists of five steps:wastewater sample collection, viral concentration, viral nucleic acid extraction, quantification of virus using quantitative RT-PCR, and dissemination of the wastewater surveillance results. This method could be used for early warning of COVID-19 outbreak in a population, monitoring COVID-19 distributions and epidemic trend, prediction of COVID-19 prevalence rate, understanding of temporal trend of SARS-COV-2 variants, and simultaneous surveillance of multiple pathogens. WBE and clinical surveillance can be used concurrently and the former is a good complement to the latter.

Determination of the ELISA kits for screening convalescence plasma with high potency of SARS-CoV-2 IgG / 中国输血杂志

【Objective】 To determine the ELISA kit for screening convalescence plasma with high potency of SARS-CoV-2 IgG by comparing and analyzing the plasma detection results of convalescent plasma collected in different periods via ELISA kits from two manufacturers and the results of mixed plasma with different potency via pseudovirus neutralization experiments. 【Methods】 Two ELISA kits from different manufacturers(named A, B) were used to detect the plasma of 269 convalescent patients collected from Feb.2020~Jan.2022. The correlation and concordance rate of the two results were analyzed to determine the kit preliminarily. According to the titers of diluted series of standard of the preliminary selected kit, 5 mixed plasma samples (G4-G128) with different potency were prepared. The correlation of ELISA IgG results of product A/B, as well as the pseudovirus neutralization test of the original strain, Omicron mutant BA.1 and BA.2 strains were analyzed. Combined with the outside-well dilution mode of the strongly positive samples, the kit for high potency of SARS-CoV-2 IgG screening was determined. 【Results】 When the internal control reference B2 was used as the standard, the detection sensitivity of product A and B was 1∶32 vs 1∶8; the detection sensitivity of product A was 4 times that of product B. The correlation Pearson r between the results given by two kits was 0.944 1(P<0.000 1). Product B with low sensitivity was primarily selected as an alternative kit. The ELISA IgG results of samples from mixed plasma showed that the order of correlation r between product A and B was 0.988. The correlation r between product A and neutralization antibody potency of the three viruses was original strain (0.978)>BA.2(0.970)>BA.1(0.799); the order of correlation r between ELISA IgG results of product B and neutralization antibody potency of the three viruses was original strain(0.994)>BA.2(0.968)>BA.1(0.804). If twice-diluted B2 was taken as the excellent standard, 55.4% of product B met the criterion, while 47.2% of product A met.For positive plasma with high IgG potency, the product B kit required a lower dilution of the sample, which was more convenient to operate. 【Conclusion】 Both of the ELISA IgG kit from product A and B can be used to screen IgG antibodies of SARS-CoV-2, while product B is more suitable for screening positive plasma with high IgG potency.

Blood immunological analysis of hemolytic disease of the fetus and newborn caused by Rh deletion type D-- / 中国输血杂志

【Objective】 To analyze the causes of a case of hemolytic disease of the fetus and newborn (HDFN),and investigate the genetic background of maternal Rh deletion D--formation. 【Methods】 Blood samples of maternal and fetus were collected, and ABO blood typing, Rh blood typing, antibody screening and identification test were performed to explore the blood group serological characteristics of Rh deletion type D--, and Rh gene sequence was performed on parturient. 【Results】 The maternal blood group was identified to be O type, D--, and the anti-Hr0 antibody against Rh high-frequency antigen was suspected to be caused by multiple pregnancies which passes through the placental barrier and enable fetus to obtain anti Hr0 antibody, leading to HDFN, with genetic testing result as RH RHCE* Ce/RHCE* Ce. 【Conclusion】 In-depth research on the formation mechanism of Rh D-- in parturient should be conducted to provide clinical value for HDFN blood exchange treatment and blood transfusion in special blood group population.

Epidemiological investigation of a school COVID-19 outbreak in Shanghai / 上海预防医学

ObjectiveTo describe a COVID-19 outbreak due to SARS-CoV-2 Omicron variant in a school and provide suggestions for COVID-19 prevention and control. MethodsData on the COVID-19 outbreak in a school in Putuo District of Shanghai were collected from November 14 to December 20， 2022. Epidemiological characteristics， incidence rate of secondary cases and response measures were described and analyzed. ResultsA total of 27 COVID-19 cases were identified infected with SARS-CoV-2 Omicron BA.5.2 variant， including 14 students （51.9%） and 13 family members / teachers living with those students （48.1%）. The first case occurred on November 14， with peak incidence during November 16-18. The median generation interval of the second generation cases was 2 （2，3） days. The index case （case 1， a student） had a clear contact history outside the school， which was found through routine examination in key populations in the school. Immediate management was conducted after the notification. All the second generation cases were exposed students in the same class with case 1， which were identified during the quarantine， whereas the third generation cases were their family members/teachers living with the second generation cases. The incidence rate within the class and school were 36.8% and 3.0%， respectively. No further social transmission was found outside the school. ConclusionEarly detection， multi-sectoral collaboration， prompt control and quarantine measures are effective in containing SARS-CoV-2 transmission. Health promotion， surveillance， ventilation and prophylactic disinfection should be reinforced in schools， office buildings and other gathering places.

Multiparametric MRI Combined with Apparent Diffusion Coefficient Histogram Analysis for Assessing Variant Histology in Urothelial Carcinoma / 中山大学学报(医学科学版)

ObjectiveTo investigate the feasibility of multiparametric MRI （mpMRI） combined with histogram analysis of apparent diffusion coefficient （ADC） in the assessment of patients with variant histology （VH） of urothelial carcinoma （UC）. MethodWe retrospectively analyzed the data of patients pathologically diagnosed with UC who underwent mpMRI in the First Affiliated Hospital of Sun Yat-sen University between March 2015 and March 2023. The patients were divided into VH group （urothelial carcinoma mixed with other histologies） and non-VH group （pure urothelial carcinoma） according to pathological results. We performed propensity score 1：1 nearest-neighbor matching on the two groups based on age and gender and 49 patients were included in each group. The regions of interest （ROIs） of the whole tumor were delineated manually by using ITK-SNAP software and Pyradiomics was applied to extract ADC histogram parameters. We compared the clinicopathological data， MRI morphological features and ADC histogram parameters between the groups. Multivariate logistic regression was used to identify independent risk factors and construct the prediction model. Receiver operating characteristic （ROC） curve analyses were performed to evaluate the diagnostic performance of these parameters for determining VH of UC. ResultsMRI morphological features including the lesion shape， vesical imaging-reporting and data system （Ⅵ-RADS）score， enhancement pattern and suspicious lymph node metastasis were markedly different between the two groups （all P < 0.05）. ADC mean， ADC median， ADC25th， ADC75th， ADC10th and ADC90th were significantly lower in patients with VH than those in non-VH group （all P<0.05）. Multivariate logistic regression analysis showed enhancement pattern， ADC25th， ADC75th and ADC mean were independent predictors （P < 0.05）. The combined model yielded the best predictive performance， with an area under the ROC curve （AUC） of 0.91 （95% CI： 0.83-0.96）. ConclusionsMpMRI combined with whole-tumor histogram analysis of ADC can serve as a reliable method for evaluating the presence of VH in UC， further to assist the clinical decision making.

Prognostic Predictive Value of ITPKB Mutation's Variant Allele Frequency in Diffuse Large B-cell Lymphoma / 肿瘤防治研究

Objective To investigate the correlation between ITPKB mutation's variant allele frequency (VAF) and prognosis of diffuse large B-cell lymphoma (DLBCL). Methods This study included 155 patients with DLBCL initially diagnosed in the People's Hospital of Xinjiang Uygur Autonomous Region from June 2014 to December 2020. Paraffin-embedded tumor tissue specimens were obtained, and tumor tissue DNA was extracted. A total of 475 hotspot genes including ITPKB were detected by the next generation sequencing to analyze the relationship of the VAF of high-frequency mutant gene with progression-free survival (PFS) and overall survival (OS). Results The mutation frequency of ITPKB was 18.71%. The PFS was significantly shorter in the patients with ITPKB mutations than in those without mutations (37 months vs. 108 months; HR=1.643, 95%CI: 0.920-2.934, P=0.093). The R-language based web tool was used to find the best VAF cutoff to differentiate prognosis. The patients were divided into two groups (VAF High vs. VAF Low+Wt) according to their VAF values. The optimal VAF threshold for ITPKB was 27.48% (HR=3.480, 95%CI: 1.70-7.13, P=0.00027). Multivariate Cox analysis was conducted using clinical indicators such as age, gender, COO classification, IPI, and LDH, and the results showed that PFS was associated with high ITPKB VAF (≥28%) (HR=3.592, 95%CI: 1.738-7.425, P < 0.001) which was an independent adverse predictor of PFS. Conclusion The high load of ITPKB mutation is an independent risk factor for the PFS of patients with DLBCL, and the VAF of ITPKB mutation has a prognostic predictive value for patients with DLBCL.