BACKGROUND: Microsatellite instability (MSI) is a key biomarker for cancer immunotherapy and prognosis. Integration of MSI testing into a next-generation-sequencing (NGS) panel could save tissue sample, reduce turn-around time and cost, and provide MSI status and comprehensive genomic profiling in single test. We aimed to develop an MSI calling model to detect MSI status along with the NGS panel-based profiling test using tumor-only samples. METHODS: From January 2019 to December 2020, a total of 174 colorectal cancer (CRC) patients were enrolled, including 31 MSI-high (MSI-H) and 143 microsatellite stability (MSS) cases. Among them, 56 paired tumor and normal samples (10 MSI-H and 46 MSS) were used for modeling, and another 118 tumor-only samples were used for validation. MSI polymerase chain reaction (MSI-PCR) was performed as the gold standard. A baseline was built for the selected microsatellite loci using the NGS data of 56 normal blood samples. An MSI detection model was constructed by analyzing the NGS data of tissue samples. The performance of the model was compared with the results of MSI-PCR. RESULTS: We first intersected the target genomic regions of the NGS panels used in this study to select common microsatellite loci. A total of 42 loci including 23 mononucleotide repeat sites and 19 longer repeat sites were candidates for modeling. As mononucleotide repeat sites are more sensitive and specific for detecting MSI status than sites with longer length motif and the mononucleotide repeat sites performed even better than the total sites, a model containing 23 mononucleotide repeat sites was constructed and named Colorectal Cancer Microsatellite Instability test (CRC-MSI). The model achieved 100% sensitivity and 100% specificity when compared with MSI-PCR in both training and validation sets. Furthermore, the CRC-MSI model was robust with the tumor content as low as 6%. In addition, 8 out of 10 MSI-H samples showed alternations in the four mismatch repair genes ( MLH1 , MSH2 , MSH6 , and PMS2 ). CONCLUSION MSI status can be accurately determined along the targeted NGS panels using only tumor samples. The performance of mononucleotide repeat sites surpasses loci with longer repeat motif in MSI calling.
Humans ; Microsatellite Instability ; Colorectal Neoplasms/diagnosis* ; Microsatellite Repeats/genetics* ; DNA Mismatch Repair

BACKGROUND: Breast cancer patients who are positive for hormone receptor typically exhibit a favorable prognosis. It is controversial whether chemotherapy is necessary for them after surgery. Our study aimed to establish a multigene model to predict the relapse of hormone receptor-positive early-stage Chinese breast cancer after surgery and direct individualized application of chemotherapy in breast cancer patients after surgery. METHODS: In this study, differentially expressed genes (DEGs) were identified between relapse and nonrelapse breast cancer groups based on RNA sequencing. Gene set enrichment analysis (GSEA) was performed to identify potential relapse-relevant pathways. CIBERSORT and Microenvironment Cell Populations-counter algorithms were used to analyze immune infiltration. The least absolute shrinkage and selection operator (LASSO) regression, log-rank tests, and multiple Cox regression were performed to identify prognostic signatures. A predictive model was developed and validated based on Kaplan-Meier analysis, receiver operating characteristic curve (ROC). RESULTS: A total of 234 out of 487 patients were enrolled in this study, and 1588 DEGs were identified between the relapse and nonrelapse groups. GSEA results showed that immune-related pathways were enriched in the nonrelapse group, whereas cell cycle- and metabolism-relevant pathways were enriched in the relapse group. A predictive model was developed using three genes ( CKMT1B , SMR3B , and OR11M1P ) generated from the LASSO regression. The model stratified breast cancer patients into high- and low-risk subgroups with significantly different prognostic statuses, and our model was independent of other clinical factors. Time-dependent ROC showed high predictive performance of the model. CONCLUSIONS A multigene model was established from RNA-sequencing data to direct risk classification and predict relapse of hormone receptor-positive breast cancer in Chinese patients. Utilization of the model could provide individualized evaluation of chemotherapy after surgery for breast cancer patients.
Humans ; Female ; Breast Neoplasms/genetics* ; East Asian People ; Neoplasm Recurrence, Local/genetics* ; Breast ; Algorithms ; Chronic Disease ; Prognosis ; Tumor Microenvironment

Objective To investigate the predictive value of preoperative frailty for pulmonary com-plications(PPCs)after cardiac surgery in elderly patients.Methods A total of 162 elderly patients,109 males and 53 females,aged 65-83 years,BMI 18-36 kg/m2,ASA physical status Ⅱ-Ⅳ,underwent elec-tive open heart surgery from July 2022 to January 2023 were collected.The patients were divided into two groups according to the occurrence of PPCs:the PPCs group(n=57)and the non-PPCs group(n=105).General information,smoking history,alcohol consumption history,EuroSCORE Ⅱ,frailty,chronic comorbidities(hypertension,diabetes mellitus,myocardial infarction,pulmonary hypertension,chronic ob-structive pulmonary disease,sleep apnea syndrome,etc.),Hb,creatinine,albumin,pulmonary function indices,left ventricular ejection fraction,type of surgery,duration of surgery,aortic clamping time,and cardiopulmonary bypass time were collected.Factors with P＜0.2 and clinically significant in the univariate regression analysis were included in the multivariate logistic regression analysis,and the predictive efficacy of the Fried frailty scale and EuroSCORE Ⅱ for PPCs were compared by the area under the ROC curve(AUC).Results PPCs occurred in 57 patients(35.2％).Multifactorial Logistic regression analysis showed that frailty(OR=3.14,95％CI 1.05-9.37,P＜0.05)and EuroSCORE Ⅱ(OR=2.16,95％CI 1.01-4.60,P＜0.05)were risk factors for the development of PPCs.The predictive power of Fried frailty scale(AUC=0.76,95％CI 0.68-0.82)was significantly higher than that of EuroSCORE Ⅱ(AUC=0.65,95％CI 0.57-0.72)(P＜0.05).Conclusion Preoperative frailty is the independent risk factors for pulmonary complications after cardiac surgery in elderly patients,and the Fried frailty scale has a better predictive efficacy compared to EuroSCORE Ⅱ,a traditional risk predictor.

Objective:This study aims to explore the relationship between the single nucleotide polymorphism (SNPs) of Apo liporoteine E (ApoE), GTP cyclohydrolase 1 (GCH1), and J subfamily member of inward rectifier potassium channel-15 (KCNJ15) gene and cognitive dysfunction in Han nationality patients with schizophrenia in Yunan province.Methods:From September 2018 to August 2020, 182 patients with schizophrenia (patient group) and 176 healthy volunteers (control group) were recruited from the Department of Psychiatry and Physical Examination Center respectively, in the First Affiliated Hospital of Kunming Medical University. The Chinese versions of PANSS and the MATRICS Cognitive Battery (MCCB) were used to evaluate psychiatric symptoms and cognitive function respectively. The SNPs of four loci of GCH1 (rs72713460), KCNJ15 (rs928771), and APOE (rs7412 and rs429358) genes were measured by fluorescence in situ hybridization. The differences of genes and genotypes between the two groups were compared. Then multiple linear regression analyses were performed in the patient group. In the regression models, the T scores of each cognitive function test were entered as dependent variables one by one, while the demographic and clinical data and the four SNPs of ApoE, GCH1, and KCNJ15 as independent variables.Results:The T scores of seven cognitive domains of MCCB were lower in the patient group than in the control group ( t=-25.65 to -18.27, all P<0.001). The genotype frequencies of ApoEε3ε4 (55/182 (30.2%) vs. 22/176 (12.5%)) and allele frequencies of ApoEε4 (65/182 (17.9%) vs. 30/176 (8.5%)) were statistically significantly higher in the patient group than in the control group (χ 2=16.64 and 13.55 respectively, both P<0.001). The genotype and allele frequency of GCH1 in patient group were higher than those in control group (χ 2=8.01 to 21.50), and the difference was statistically significant ( P<0.001 or P<0.05). In the patient group, the T scores of 7 cognitive domains were lower in ApoEε4 allele carriers than in non-carriers ( t=4.99 to 17.69), the T scores of 6 cognitive domains were lower in GCH1-T allele carriers than in non-carriers ( t=5.75 to 13.36), and the T scores of 5 cognitive domains were higher in KCNJ15-G allele carriers than in non-carriers ( t=-2.99 to -2.48). In schizophrenia patients, multiple regression analyses showed that the cognitive domains of information processing speed and word learning were related to carrying ApoEε4 and GCH1-T allele. Conclusion:There is pervasive and significant cognitive dysfunction in Han nationality patients with schizophrenia in Yunan province. The polymorphism of ApoE and GCH1 genes may be related to the pathogenesis of cognitive dysfunction in schizophrenia.

Objective:This study aims to explore the relationship between the single nucleotide polymorphism (SNPs) of Apo liporoteine E (ApoE), GTP cyclohydrolase 1 (GCH1), and J subfamily member of inward rectifier potassium channel-15 (KCNJ15) gene and cognitive dysfunction in Han nationality patients with schizophrenia in Yunan province.Methods:From September 2018 to August 2020, 182 patients with schizophrenia (patient group) and 176 healthy volunteers (control group) were recruited from the Department of Psychiatry and Physical Examination Center respectively, in the First Affiliated Hospital of Kunming Medical University. The Chinese versions of PANSS and the MATRICS Cognitive Battery (MCCB) were used to evaluate psychiatric symptoms and cognitive function respectively. The SNPs of four loci of GCH1 (rs72713460), KCNJ15 (rs928771), and APOE (rs7412 and rs429358) genes were measured by fluorescence in situ hybridization. The differences of genes and genotypes between the two groups were compared. Then multiple linear regression analyses were performed in the patient group. In the regression models, the T scores of each cognitive function test were entered as dependent variables one by one, while the demographic and clinical data and the four SNPs of ApoE, GCH1, and KCNJ15 as independent variables.Results:The T scores of seven cognitive domains of MCCB were lower in the patient group than in the control group ( t=-25.65 to -18.27, all P<0.001). The genotype frequencies of ApoEε3ε4 (55/182 (30.2%) vs. 22/176 (12.5%)) and allele frequencies of ApoEε4 (65/182 (17.9%) vs. 30/176 (8.5%)) were statistically significantly higher in the patient group than in the control group (χ 2=16.64 and 13.55 respectively, both P<0.001). The genotype and allele frequency of GCH1 in patient group were higher than those in control group (χ 2=8.01 to 21.50), and the difference was statistically significant ( P<0.001 or P<0.05). In the patient group, the T scores of 7 cognitive domains were lower in ApoEε4 allele carriers than in non-carriers ( t=4.99 to 17.69), the T scores of 6 cognitive domains were lower in GCH1-T allele carriers than in non-carriers ( t=5.75 to 13.36), and the T scores of 5 cognitive domains were higher in KCNJ15-G allele carriers than in non-carriers ( t=-2.99 to -2.48). In schizophrenia patients, multiple regression analyses showed that the cognitive domains of information processing speed and word learning were related to carrying ApoEε4 and GCH1-T allele. Conclusion:There is pervasive and significant cognitive dysfunction in Han nationality patients with schizophrenia in Yunan province. The polymorphism of ApoE and GCH1 genes may be related to the pathogenesis of cognitive dysfunction in schizophrenia.

OBJECTIVE: To compare various models of diffusion-weighted imaging including monoexponential apparent diffusion coefficient (ADC), biexponential (fast diffusion coefficient [Df], slow diffusion coefficient [Ds], and fraction of fast diffusion), stretched-exponential (distributed diffusion coefficient and anomalous exponent term [α]), and kurtosis (mean diffusivity and mean kurtosis [MK]) models in the differentiation of renal solid masses. MATERIALS AND METHODS: A total of 81 patients (56 men and 25 women; mean age, 57 years; age range, 30–69 years) with 18 benign and 63 malignant lesions were imaged using 3T diffusion-weighted MRI. Diffusion model selection was investigated in each lesion using the Akaike information criteria. Mann-Whitney U test and receiver operating characteristic (ROC) analysis were used for statistical evaluations. RESULTS: Goodness-of-fit analysis showed that the stretched-exponential model had the highest voxel percentages in benign and malignant lesions (90.7% and 51.4%, respectively). ADC, Ds, and MK showed significant differences between benign and malignant lesions (p < 0.05) and between low- and high-grade clear cell renal cell carcinoma (ccRCC) (p < 0.05). α was significantly lower in the benign group than in the malignant group (p < 0.05). All diffusion measures showed significant differences between ccRCC and non-ccRCC (p < 0.05) except Df and α (p = 0.143 and 0.112, respectively). α showed the highest diagnostic accuracy in differentiating benign and malignant lesions with an area under the ROC curve of 0.923, but none of the parameters from these advanced models revealed significantly better performance over ADC in discriminating subtypes or grades of renal cell carcinoma (RCC) (p > 0.05). CONCLUSION: Compared with conventional diffusion parameters, α may provide additional information for differentiating benign and malignant renal masses, while ADC remains the most valuable parameter for differentiation of RCC subtypes and for ccRCC grading.
Carcinoma, Renal Cell ; Diffusion ; Female ; Humans ; Magnetic Resonance Imaging ; Male ; ROC Curve

Objective: To analyze the clinicopathological characteristics and prognosis of diffuse midline glioma (DMG) with H3K27M mutation. Methods: Thirty cases of DMG were collected in Guangdong Sanjiu Brain Hospital from October 2016 to May 2018. The patients′ clinicopathological data including age, tumor site and histological grade, treatment and follow-up data were collected and analyzed. Results: There were 21 males and 9 females, with a mean age of 26 years (range 5-53 years). Fourteen tumors were located in thalamus, 12 in brainstem (one involved both thalamus and brainstem), and one each in hypothalamus, fourth ventricle, and sellar region, respectively. Two cases presented as diffuse intracranial lesions. Three cases (10.0%) were of WHO grade Ⅰ, 10 cases (33.3%) were grade Ⅱ, eight cases (26.7%) were grade Ⅲ, and nine cases (30.0%) were grade Ⅳ.All patients with gradeⅠ tumors were older than 20 years. Histologically, all were pilocytic astrocytoma-like. Immunohistochemical staining demonstrated that all tumors were IDH1 negative. Twenty-eight tumors showed diffuse expression of H3K27M, and two showed focal expression. Twenty-one tumors(100.0%, 21/21) showed absent expression of H3K27me3. Sixteen tumors (57.1%, 16/28) showed strongly positive expression of p53, and ATRX was negative in eight tumors (38.1%, 8/21). The Ki-67 proliferation index ranged from 5% to 40%. Eight cases (including two cases of H3K27M expression of individual cells) showed K27M mutation in H3F3A gene. Intracranial and spinal cord dissemination occurred in six cases (20.0%, 6/30). Median progression-free survival (PFS) was 9.5 months and median overall survival (OS) was 34 months. Mean PFS was 11.2 months and mean OS was 24.3 months. Compared with adults (>20 years old), children/adolescents (no more than 20 years old) had significantly shorter median OS (8 months vs. 34 months, P=0.013). There was no significant difference in PFS and OS between DMGs located in the brain stem/thalamus and other sites within midline (P>0.05). There was no significant difference in PFS and OS between WHO grade ⅠDMGs and WHO grade Ⅱ-Ⅳ DMGs (P>0.05). Conclusions DMGs occur more commonly in children and adolescents with male predominance. DMGs present with WHO Ⅰ-Ⅳ tumors morphologically, and pilocytic astrocytoma-like lesions with WHO Ⅰ are more common in adults. Expression of H3K27M but not H3K27me3 is helpful for diagnosis of DMG. The prognosis of children/adolescents is significantly worse than that of adults, whereas histological grade and tumor location do not affect prognosis.

Objective:To investigate the current status of the postpartum depression in Kaifu District in Changsha,and to explore the influential factors for postpartum depression.Methods:We selected the mothers,who had a delivery and met the inclusion criteria in Changsha during 2015,as the participants and established a prospective birth cohort study.The social demographic characteristics and health-related information for the mothers and their families were collected by using self-made questionnaire.The mothers' depression symptoms after one month postpartum were assessed by the Edinburgh Postnatal Depression Scale.We used the structural equation model to analyze the influential factors for postpartum depression.Results:A total of 961 cases were investigated.82 of them whose scores of EPDS were ≥ 9 points,and the incidence of PPD was 8.2％.The results of structural equation model revealed the influential factors and their correlations with postpartum depression.It has been shown that maternal age,maternal education level,per capita income of family,intention of pregnancy,pregnancy-related complications,mode of conception,mode of delivery,feeding patterns,birth weight,baby gender,and infant illness could exert effects on postpartum depression.Conclusion:The incidence of postpartum depression in Kaifu District is at a low level and the structural equation model can be applied to analyze the influential factors and their relations with postpartum depression.

Objective: To investigate the association between hepatic controlled attenuation parameter (CAP) and metabolic syndrome (MetS) and the correlation of CAP and its changes with the incidence of MetS. Methods: A total of 2461 subjects who underwent physical examination from July 2013 to September 2015 were enrolled. Spearman correlation analysis was used to investigate the correlation of CAP with the number of MetS components and each MetS component, and the chi-square test was used to investigate the prevalence rates of MetS and each component under different CAP levels. Logistic regression analysis was used to analyze the odds ratio (95% confidence interval (CI)) of MetS under different CAP levels. A total of 230 subjects without baseline MetS were selected; in a prospective cohort study, these subjects were divided into groups according to the baseline CAP, change in CAP, and percent change in CAP, and the chi-square test was performed to compare the incidence of MetS. The Cox regression analysis was used to analyze the values of baseline CAP, change in CAP, and percent change in CAP in predicting MetS. Results: CAP was positively correlated with the number of MetS components (r = 0.309, P < 0.01) and significantly correlated with all components. There were significant differences in the prevalence rates of MetS and its components under different CAP levels (< 238 dB/m, 238-258 dB/m, 259-291 dB/m, and ≥292 dB/m) (P < 0.05). After the adjustment for sex and age, with < 238 dB/m as a reference, the odds ratios (95% CI) of MetS in patients with CAP levels of 238-258 dB/m, 259-291 dB/m, and ≥292 dB/m were 1.784 (1.369-2.325), 2.936 (2.292-3.760), and 4.363 (3.435-5.543), respectively (all P < 0.05). Follow-up data showed that 28 patients (12.2%) developed MetS. After the adjustment for related factors, the hazard ratios (95% CI) of MetS in patients with baseline CAP > 238 dB/m, change in CAP > 30 dB/m, and percent change in CAP > 25.0% were 3.337 (1.163-9.569), 7.732 (2.453-24.366), and 11.656 (3.329-40.813), respectively (all P < 0.05). Conclusion CAP is closely associated with MetS and its components. CAP and its change can be used to predict the risk of MetS.

Objective To explore the accuracy of endoscopic ultrasonography (EUS) for evaluating T3 esophageal squamous cell carcinoma (ESCC).Methods The retrospective cross-sectional study was conducted.The clinicopathological data of 733 patients diagnosed with T3 ESCC by preoperative EUS who were admitted to the Sun Yat-sen University Cancer Center from January 2003 to December 2015 were collected.All the patients underwent radical resection of ESCC.The postoperative pathological stage as a gold standard,the accuracy,overstaged and understaged rates of clinical staging by preoperative EUS were assessed.Observation indicators:(1) comparison between clinical T staging evaluated by preoperative EUS and postoperative pathological T staging;(2) follow-up and survival situations.Follow-up using outpatient examination and telephone interview was performed to detect patients' diseases and postoperative survival up to December 30,2016.Overall survival time was from operation time to death or last effective follow-up.Measurement data with normal distribution were represented as (x)±s.Measurement data with skewed distribution were described as M (range).Count data were represented as cases and percentage.The survival curve was drawn by the Kaplan-Meier method,and survival analysis was done using the Log-rank test.Results (1) Comparison between clinical T staging evaluated by preoperative EUS and postoperative pathological T staging:all the 733 patients were confirmed as T3 ESCC by preoperative EUS.Postoperative pathological diagnosis showed that 9 patients were detected in pT1b,87 in pT2,630 in pT3 and 7 in pT4a.The accuracy,overstaged and understaged rates of preoperative EUS in evaluating T3 ESCC were 85.95％(630/733),13.10％(96/733) and 0.95％(7/733),respectively.N0,N1,N2 and N3 of postoperative pathological N stage were respectively detected in 329,247,110 and 47 patients.Twenty-seven,323 and 383 patients were in stage Ⅰ,Ⅱ and Ⅲ of TNM stage,respectively.The high-,moderate-and lowdifferentiated tumors were respectively detected in 125,403 and 205 patients.(2) Follow-up and survival situations:among 733 patients,639 were followed up for 1.0-153.0 months,with a median time of 29.0 months.The median survival time,1-,3-,5-year overall survival rates were 53.0 months (range,37.7-68.3 months),85.3％,58.1％ and 48.2％ in 733 patients,respectively.The 5-year overall survival rate was 75.2％ in 9 patients with pT1b,63.0％ in 87 patients with pT2,46.3％ in 630 patients with pT3 and 0 in 7 patients with pT4a,respectively,with a statistically significant difference (x2=24.089,P＜0.05).Conclusion There is a higher accuracy of EUS for evaluating T3 ESCC,however,the stage migration should be noted.