BACKGROUND: Neoadjuvant chemoradiotherapy followed by radical surgery has been a common practice for patients with locally advanced rectal cancer, but the response rate varies among patients. This study aimed to develop a ResNet-Vision Transformer based magnetic resonance imaging (MRI)-endoscopy fusion model to precisely predict treatment response and provide personalized treatment. METHODS: In this multicenter study, 366 eligible patients who had undergone neoadjuvant chemoradiotherapy followed by radical surgery at eight Chinese tertiary hospitals between January 2017 and June 2024 were recruited, with 2928 pretreatment colonic endoscopic images and 366 pelvic MRI images. An MRI-endoscopy fusion model was constructed based on the ResNet backbone and Transformer network using pretreatment MRI and endoscopic images. Treatment response was defined as good response or non-good response based on the tumor regression grade. The Delong test and the Hanley-McNeil test were utilized to compare prediction performance among different models and different subgroups, respectively. The predictive performance of the MRI-endoscopy fusion model was comprehensively validated in the test sets and was further compared to that of the single-modal MRI model and single-modal endoscopy model. RESULTS: The MRI-endoscopy fusion model demonstrated favorable prediction performance. In the internal validation set, the area under the curve (AUC) and accuracy were 0.852 (95% confidence interval [CI]: 0.744-0.940) and 0.737 (95% CI: 0.712-0.844), respectively. Moreover, the AUC and accuracy reached 0.769 (95% CI: 0.678-0.861) and 0.729 (95% CI: 0.628-0.821), respectively, in the external test set. In addition, the MRI-endoscopy fusion model outperformed the single-modal MRI model (AUC: 0.692 [95% CI: 0.609-0.783], accuracy: 0.659 [95% CI: 0.565-0.775]) and the single-modal endoscopy model (AUC: 0.720 [95% CI: 0.617-0.823], accuracy: 0.713 [95% CI: 0.612-0.809]) in the external test set. CONCLUSION The MRI-endoscopy fusion model based on ResNet-Vision Transformer achieved favorable performance in predicting treatment response to neoadjuvant chemoradiotherapy and holds tremendous potential for enabling personalized treatment regimens for locally advanced rectal cancer patients.
Humans ; Rectal Neoplasms/diagnostic imaging* ; Magnetic Resonance Imaging/methods* ; Male ; Female ; Middle Aged ; Neoadjuvant Therapy/methods* ; Aged ; Adult ; Chemoradiotherapy/methods* ; Endoscopy/methods* ; Treatment Outcome

Approximately 60% of colorectal cancer (CRC) patients exhibit TP53 mutations, which are strongly associated with tumor progression, chemotherapy resistance, and an unfavorable prognosis. However, targeting p53 has historically been challenging, and currently, there are no approved p53-based therapeutics for clinical use worldwide. In this study, we discovered that ubiquitin carboxyl terminal hydrolase L3 (UCHL3) plays a crucial role in high-level glycolysis, enhanced stem-like properties, and 5-fluorouracil (5-FU) chemoresistance in TP53-mutant CRC by exerting its deubiquitinating enzyme activity to stabilize α-enolase (ENO1) protein. Notably, we identified a newly Food and Drug Administration (FDA)-approved drug, pacritinib, that potently suppresses UCHL3 expression by blocking the janus kinase 2 (JAK2)-signal transducer and activator of transcription 3 (STAT3) pathway in TP53-mutant CRC. Furthermore, Pacritinib was demonstrated to effectively inhibit glycolysis and improve the sensitivity to 5-FU chemotherapy in TP53-mutant CRC. Our findings suggest that targeting the JAK2-STAT3-UCHL3-ENO1 axis is a promising strategy to suppress glycolysis and enhance the efficacy of 5-FU chemotherapy in TP53-mutant CRC. Pacritinib shows potential for clinical application in the treatment of TP53-mutant CRC.

Objective To analyze the dynamic change in placental growth factor(PLGF)level in patients with preeclampsia(PE)and its role in predicting pregnancy outcomes.Methods A retrospective cohort study was conducted on 198 PE patients admitted to Department of Obstetrics of Tianjin Beichen Hospital from January 2021 to January 2024.Among them,151 cases were identified as non-severe PE and 47 cases as severe PE.During the same period,another 100 healthy pregnant women were included in the department and served as the control group.According to the final pregnancy status of the PE patients,they were divided into an adverse outcome group(88 cases)and a good outcome group(110 cases).Locally Weighted Scatterplot Smoothing(LOWESS)was used to analyze the relationship between vascular endothelial function indicators and PLGF level.Logistic regression was employed to identify the influencing factors for adverse pregnancy outcomes.Receiver operating characteristic(ROC)curve was plotted to evaluate the value of PLGF level for predicting adverse pregnancy outcomes in patients with non-severe PE and severe PE.Results The PLGF level was in a peak shape at different gestational weeks,relatively low at 28～29+6 weeks of gestation,gradually increasing with the increment of gestational weeks,reaching a peak at 30～31+6 weeks of gestation,and then gradually decreased(P<0.05).The PLGF level was gradually reduced in the control group,non-severe PE group,and severe PE group in turn(P<0.05).LOWESS analysis showed that the PLGF level exhibited certain nonlinear relationship with soluble fms-like tyrosine kinase receptor 1(sFlt-1),vascular endothelial growth factor(VEGF),nitric oxide(NO),thrombomodulin(TM),thromboxane A2(TXA2),and Von Willebrand factor(VwF).The results of logistic regression analysis indicated that after gradually eliminating collinearity confounding factors and adjusting for each covariate,there was still an independent correlation between the PLGF level at 28～29+6 gestational weeks and pregnancy outcome(OR=0.593,95%CI:0.583～0.778,P<0.001).After converting the PLGF level into a binary variable,there was an independent correlation between high PLGF level and pregnancy outcome(OR=0.773,95%CI:0.671～0.885,P<0.001).Compared with the quintile with the lowest PLGF(Q1),as the PLGF level gradually increased(Q2 to Q5),the correlation effect values were(OR=0.765,95%CI:0.639～0.837,P=0.092),(OR=0.752,95%CI:0.624～0.818,P=0.056),(OR=0.696,95%CI:0.615～0.813,P=0.027),and(OR=0.642,95%CI:0.591～0.733,P<0.001),and the trend test was statistically significant(Ptrend<0.001).ROC curve analysis revealed that the area under the ROC curve(AUC)of serum PLGF level at 28-29+6 gestational weeks in predicting adverse pregnancy outcomes in non-severe PE patients was 0.830(95%CI:0.635～0.917),the optimal critical threshold was 75.47 ng/L,the sensitivity was 88.37%,the specificity was 71.30%,the positive predictive value was 55.07%,and the negative predictive value was 93.90%.Its AUC value of the level for the prediction in patients with severe PE was 0.874(95%CI:0.677～0.923),the optimal critical threshold was 38.53 ng/L,the sensitivity was 88.89%,the specificity was 50.00%,the positive predictive value was 97.56%,and the negative predictive value was 16.67%.Conclusion At 28～29+6 gestational weeks,PLGF has an independent correlation with pregnancy outcomes and shows a good predictive performance for adverse pregnancy outcomes in patients with non-severe PE and severe PE.

The clinical data of a case with neonatal hypertrophic cardiomyopathy (HCM) admitted to the Department of Pediatrics, Beijing Anzhen Hospital, Capital Medical University in July 2020 was retrospectively analyzed.The child developed hyperbilirubinemia and severe anemia within 1 hour after birth.The direct Coombs test was negative.The diagnosis of MN hemolytic disease was confirmed by positive results of both the indirect Coombs test and the maternal indirect Coombs test.Echocardiography and cardiac magnetic resonance imaging confirmed the presence of HCM, and genetic testing showed SCN5A and ANK2 gene heterozygous mutations.After treatment with blue light irradiation, intravenous immunoglobulin, red blood cell washing, Dexamethasone and sodium phosphocreatine, the condition improved and the patient was discharged.During the follow-up period, delayed hemolysis occurred 1.5 months after birth, and thus the patient received re-infusion of immunoglobulin and washing of red blood cells.A scalp hemangioma and a break in milk intake were detected 2 and 7 months after birth, respectively.Treatment with Propranolol, Captopril, Hydrochlorothiazide, and Spironolactone improved the condition.The patient was followed up until August 2024, with clinical symptoms significantly improved, no occurrence of anemia, and no further thickening or progression of the myocardium.

The clinical data of a case with neonatal hypertrophic cardiomyopathy (HCM) admitted to the Department of Pediatrics, Beijing Anzhen Hospital, Capital Medical University in July 2020 was retrospectively analyzed.The child developed hyperbilirubinemia and severe anemia within 1 hour after birth.The direct Coombs test was negative.The diagnosis of MN hemolytic disease was confirmed by positive results of both the indirect Coombs test and the maternal indirect Coombs test.Echocardiography and cardiac magnetic resonance imaging confirmed the presence of HCM, and genetic testing showed SCN5A and ANK2 gene heterozygous mutations.After treatment with blue light irradiation, intravenous immunoglobulin, red blood cell washing, Dexamethasone and sodium phosphocreatine, the condition improved and the patient was discharged.During the follow-up period, delayed hemolysis occurred 1.5 months after birth, and thus the patient received re-infusion of immunoglobulin and washing of red blood cells.A scalp hemangioma and a break in milk intake were detected 2 and 7 months after birth, respectively.Treatment with Propranolol, Captopril, Hydrochlorothiazide, and Spironolactone improved the condition.The patient was followed up until August 2024, with clinical symptoms significantly improved, no occurrence of anemia, and no further thickening or progression of the myocardium.

Objective To explore the relationship between the serum level of placental growth factor(PLGF)and ultrasonic blood flow parameters and pregnancy outcome in patients with late-onset preeclampsia(LOPE).Methods A total of 152 patients with LOPE were selected and divided into the P1(＜12.00 ng/L)group,the P2(12.00-56.73 ng/L)group,the P3(＞56.73-89.41 ng/L)group and the P4(＞89.41 ng/L)group according to serum level of PLGF.There were 38 cases in each group.The clinical data,uterine artery pulsatility index(PI),resistance index(RI),peak systolic velocity(S)/end-diastolic velocity(D)and adverse pregnancy outcome were compared between the four groups.The relationship between PLGF level and clinical characteristics was analyzed by linear regression analysis.The influence of LOPE severity on the relationship between PLGF and ultrasonic blood flow parameters was analyzed by stratified interactive analysis.Multivariate generalized linear mixed effect model was used to analyze the relationship between PLGF level and adverse pregnancy outcome in patients with LOPE.Results The diastolic blood pressure,24 h urinary protein,PI,RI and S/D decreased significantly with the increase of PLGF level(P＜0.05).The proportion of severe LOPE and systolic blood pressure were significantly higher in the P1 group than those of the other groups(P＜0.05),and the above indexes were influencing factors of the level of PLGF(P＜0.05).The results of stratified interactive test showed that the LOPE severity did not affect the relationship between PLGF and ultrasonic blood flow parameters.There were significant differences in the incidence of HELLP syndrome,fetal growth restriction,fetal distress,premature delivery and neonatal asphyxia between patients with different PLGF levels(P＜0.05).The incidence of preterm delivery was higher in the P1 group than that in the other groups,and the other adverse pregnancy outcomes were higher in the P3 group and P4 group.Conclusion Serum PLGF levels affect uterine artery blood flow parameters and adverse pregnancy outcome in patients with LOPE.

Abstract: Objective　To investigate the expression level and clinical significance of serum liver fibrosis-associated lncRNA1 (lnc-LFAR1) in patients with chronic hepatitis B cirrhosis, aiming to analyze its correlation with interleukin-6 (IL-6), interleukin-1β (IL-1β), and liver function. Methods　Patients with chronic hepatitis B (CHB) cirrhosis and CHB diagnosed and treated in Dongguan City People's Hospital from March 2016 to December 2019 were selected and divided into the liver cirrhosis group (n=80) and the CHB group (n=80), and 80 healthy people with physical examination during the same period were selected as healthy group. The serum levels of lnc-LFAR1, interleukin-6 (IL-6), albumin (ALB), interleukin-1β (IL-1β) and liver function indicators, including albumin (ALB) and alanine aminotransferase (ALT) were measured and analyzed. The correlation between serum lnc-LFAR1 expression level and IL-6, IL-1β was assessed, and the levels of lnc-LFAR1, IL-6, IL-1β, ALB and ALT were compared among patients with CHB cirrhosis of different Child-Pugh grades. Results The serum levels of lnc-LFAR1, IL-6, IL-1β and ALT in the patients with liver cirrhosis [(1.85± 0.62), (41.76±13.92) ng/mL, (7.78±1.95) pg/mL, (148.37±29.67) U/L] were higher than those in the CHB group [(1.42±0.47), (23.56± 7.85) ng/mL, (5.42±1.41) pg/mL, (87.59±17.52) U/L] and the healthy group [(1.01±0.34), (6.70±2.23) ng/mL, (3.13± 0.78) pg/mL, (15.44±3.10) U/L] (P<0.05), while the ALB levels (30.54±3.82) g/L were lower than those in the CHB group (37.27±4.34) g/L and the healthy group (45.26±5.66) g/L (P<0.05). Serum lnc-LFAR1, IL-6, IL-1β and ALT levels in the CHB group were higher than those in the healthy group (P<0.05), and ALB levels were lower than those in the healthy group (P<0.05); the serum levels of lnc-LFAR1, IL-6, IL-1β in patients with CHB cirrhosis were negatively correlated with ALB (P<0.05), and positively correlated with ALT (P<0.05); the serum expression level of lnc-LFAR1 in patients with CHB cirrhosis was positively correlated with IL-6 and IL-1β (r=0.598, 0.571, P<0.05); with the increase of Child-Pugh grade, the serum levels of lnc-LFAR1, IL-6, IL-1β, and ALT in patients with CHB cirrhosis gradually increased (P<0.05), and the level of ALB gradually decreased (P<0.05). Conclusions Serum lnc-LFAR1 expression level is higher in patients with CHB cirrhosis, which is obviously related to IL-6, IL-1β, ALB and ALT. Therefore, the evaluation of serum lnc-LFAR1 expression level is helpful in the clinical assessment of the condition of CHB cirrhosis patients.

BACKGROUND: The effect of intra-operative chemotherapy (IOC) on the long-term survival of patients with colorectal cancer (CRC) remains unclear. In this study, we evaluated the independent effect of intra-operative infusion of 5-fluorouracil in combination with calcium folinate on the survival of CRC patients following radical resection. METHODS: 1820 patients were recruited, and 1263 received IOC and 557 did not. Clinical and demographic data were collected, including overall survival (OS), clinicopathological features, and treatment strategies. Risk factors for IOC-related deaths were identified using multivariate Cox proportional hazards models. A regression model was developed to analyze the independent effects of IOC. RESULTS: Proportional hazard regression analysis showed that IOC (hazard ratio [HR]=0.53, 95% confidence intervals [CI] [0.43, 0.65], P  < 0.001) was a protective factor for the survival of patients. The mean overall survival time in IOC group was 82.50 (95% CI [80.52, 84.49]) months, and 71.21 (95% CI [67.92, 74.50]) months in non-IOC group. The OS in IOC-treated patients were significantly higher than non-IOC-treated patients ( P  < 0.001, log-rank test). Further analysis revealed that IOC decreased the risk of death in patients with CRC in a non-adjusted model (HR=0.53, 95% CI [0.43, 0.65], P  < 0.001), model 2 (adjusted for age and gender, HR=0.52, 95% CI [0.43, 0.64], P  < 0.001), and model 3 (adjusted for all factors, 95% CI 0.71 [0.55, 0.90], P  = 0.006). The subgroup analysis showed that the HR for the effect of IOC on survival was lower in patients with stage II (HR = 0.46, 95% CI [0.31, 0.67]) or III disease (HR=0.59, 95% CI [0.45, 0.76]), regardless of pre-operative radiotherapy (HR=0.55, 95% CI [0.45, 0.68]) or pre-operative chemotherapy (HR=0.54, 95% CI [0.44, 0.66]). CONCLUSIONS: IOC is an independent factor that influences the survival of CRC patients. It improved the OS of patients with stages II and III CRC after radical surgery. TRIAL REGISTRATION chictr.org.cn, ChiCTR 2100043775.
Humans ; Fluorouracil/therapeutic use* ; Leucovorin/therapeutic use* ; Colorectal Neoplasms/pathology* ; Retrospective Studies ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Proportional Hazards Models ; Prognosis

OBJECTIVE: To detect variants of the MMACHC gene among 110 ethnic Han Chinese pedigrees affected with metabolic deficiency methylmalonic acidemia (MMA) of cobalamin C (cblC). METHODS: Peripheral blood samples were collected from the probands and their parents. Following DNA extraction, the coding regions of the MMACHC gene were subjected to PCR amplification, Sanger sequencing and quantitative PCR assaying. For 48 pedigrees, chorionic villus samples were taken for prenatal genetic diagnosis. RESULTS: Thirty five types of variants were detected among the 110 pedigrees, which included missense, nonsense, frameshifting, splicing variants and exonic deletions. Most variants have occurred in exons 4 (73.18%). The detection rate for c.609G>A (p.Trp203Ter) variant was the highest (33.64%), followed by c.658_660delAAG (12.27%), c.567dupT (9.09%) and c.80A>G (6.82%). Two variants, namely c.57_58insT (p.Gly20Trpfs*14) and c.505_506delAT (p.Ile169Argfs*12), were unreported previously and both were of frameshifting types. For the 48 pedigrees undergoing prenatal diagnosis, 14 fetuses were found to be normal, 24 have carried heterozygous variants, the remaining 10 have carried compound heterozygous or homozygous variants. CONCLUSION The discovery of the two novel variants has expanded the spectrum of the MMACHC gene variants among ethnic Han population. Above finding has provide a basis for the prenatal diagnosis and genetic counseling for the affected pedigrees.
Amino Acid Metabolism, Inborn Errors/genetics* ; China ; DNA ; Female ; Humans ; Mutation ; Oxidoreductases/genetics* ; Pedigree ; Pregnancy ; Prenatal Diagnosis ; Vitamin B 12/genetics*

Objective:To explore the latent categories of child security and analyze domain-specific roles of child neglect on security among children aged 10-13 years.Methods:From October to December 2019, the security questionnaire (SQ), child neglect scale (CNS) and Buss-Perry aggression questionnaire (BPAQ) were used to investigate 577 children aged 10-13 years. Mplus 7.0 software was used for latent profile analysis (LPA) to explore the latent categories of child security. SPSS 22.0 software was used for multinomial Logistic regression to examine the effects of different domains of child neglect on the child security categories.Results:(1) Child security was divided into three categories named "medium-slightly low-security subgroup (48.9%)" , "high-security subgroup (31.8%)" , and "inability control subgroup (19.3%)" (entropy = 0.90, Lo-Mendell-Rubin likelihood, and Bootstrapped likelihood ratio test, all P<0.01). (2) Child security(35.06±6.08, 51.49±4.99, 69.67±6.13, F=1 378.09, P<0.01), neglect(71.09±20.58, 59.96±12.90, 50.76±9.27, F=74.50, P<0.01), and aggression(54.31±15.23, 46.44±12.46, 34.19±12.61, F=90.95, P<0.01) were significantly different among the "medium-slightly low-security subgroup" , "high-security subgroup" , and "inability control subgroup" . (3)Compared with "high-security subgroup" , the proportion of children with poor parental relationship and low paternal education level were higher in the other two subgroups(all P<0.05), while the proportion of children in the fifth grade were lower(all P<0.05). (4)In " inability control subgroup" , safe neglect had no impact on security( B=0.01, OR=1.02, 95% CI=0.91-1.13, P>0.05), while physical neglect ( B=0.13, OR=1.14, 95% CI=1.01-1.28), affection neglect( B=0.14, OR=1.15, 95% CI=1.07-1.23), and communication neglect( B=0.15, OR=1.16, 95% CI=1.03-1.30) predicted the "inability control subgroup" (all P<0.05). Only communication neglect predicted the "medium-slightly low-security subgroup" ( B=0.16, OR=1.17, 95% CI=1.07-1.28, P<0.01). Conclusion:Security is heterogenous with three latent categories among Children aged 10-13 years. Child neglect plays domain-specific roles in different child security categories.