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 investigate the association between CITP/MMP-1 ratio and the severity of Myocardial fibrosis (MF) in patients with Chronic Heart failure (CHF) and its diagnostic and prognostic value in patients with MF.Methods:A retrospective study was conducted to select 110 cases [86 males, (56.60±11.15) years old;24 females, (60.06±12.02) years old] who were hospitalized in the Department of Cardiology, Teda International Cardiovascular Hospital from May 18, 2021 to February 30, 2022 and underwent magnetic magnetic examination. Serum CITP and MMP-1 were detected by enzyme-linked immunoassay and CITP/MMP-1 ratio was calculated. Plasma brain natriuretic peptide (BNP) was detected by automatic chemiluminescence analyzer. Anova and non-parametric test were used to compare the difference of indexes among all groups. Spearman analysis was used to analyze the correlation between serum collagen metabolites and the severity of myocardial fibrosis. Logistic regression analysis was performed for multivariate analysis, and ROC curve was used to evaluate the auxiliary diagnostic value of related indexes. Major adverse cardiac events within 1 year after discharge were recorded, including cardiogenic death, HF rehospitalization, malignant arrhythmia, and myocardial infarction. The risk factors of poor prognosis were analyzed by Cox regression. Patients were divided by the median value of CITP/MMP-1 ratio or the median value of CITP/MMP-1 ratio and BNP. Survival analysis was performed by Kaplan-Meier and Log Rank test was performed.Results:Serum MMP-1 and BNP in LGE (+) group were higher than those in LGE (-) group (1.79 ng/ml > 0.91 ng/ml, Z=-2.924; 503 pg/ml > 367 pg/ml, Z=-1.932; P<0.05); The CITP/MMP-1 ratio in the LGE (+) group was lower than that in the LGE (-) group (3.84 < 10.85, Z=-3.601, P<0.001). MMP-1 in CHF with arrhythmia group was higher than that in CHF group (1.98 ng/ml > 1.25 ng/ml, Z=-2.016), while CITP/MMP-1 ratio was lower than that in CHF group (3.25 < 5.73, Z=-2.751), all P<0.05. CITP/MMP-1 ratio in CHF patients was negatively correlated with the severity of MF ( r=-0.363, P<0.001), and BNP and MMP-1 were positively correlated with the severity of MF ( r=0.267, r=0.264, P<0.05). Serum BNP was positively correlated with collagen metabolite MMP-1 and negatively correlated with CITP/MMP-1 ratio (all P<0.05). Logistic multivariate regression analysis showed that only CITP/MMP-1 was a predictor of myocardial fibrosis, with an OR value of 0.624 ( P=0.005). ROC curve was used to evaluate serum BNP, MMP-1 and CITP/MMP-1 ratio in the diagnosis of myocardial fibrosis in HF patients, with AUC of 0.653, 0.696 and 0.754, respectively. The accuracy of CITP/MMP-1 ratio in diagnosing fibrosis was better than that of BNP by comparing their AUC, and the difference was statistically significant ( Z=-3.808, P<0.001). Cox regression analysis showed that CITP/MMP-1 ≤3.84 was a risk factor for poor prognosis, OR=2.647 ( P=0.009). Kaplan-Meier survival analysis at 1-year follow-up showed that the survival rate of the group with lower CITP/MMP-1 ratio was significantly lower than that of the group with higher CITP/MMP-1 ratio ( P=0.014). The survival rate of CITP/MMP-1 increased and BNP decreased group was higher than that of CITP/MMP-1 decreased and BNP increased group ( P=0.011). Conclusions:The ratio of CITP/MMP-1 can be used as a negative correlation indicator of the degree of cross-linking, which is better than BNP in the evaluation of MF, and has a good auxiliary diagnostic value for myocardial fibrosis in patients with chronic heart failure, and is expected to become a protective indicator for patients with chronic heart failure and be used in clinical evaluation of myocardial fibrosis. CITP/MMP-1 ratio is associated with the incidence of major adverse cardiac events, and CITP/MMP-1 ≤3.84 can be used as a predictor of prognostic adverse cardiovascular events in CHF patients.

Objective To screen the most suitable medium for Brucella drug susceptibility test, and observe the resistance of human derived Brucella to different antibiotics. Methods Totally 180 strains of Brucella isolated from 25 provinces (municipalities, autonomous regions) in recent years were taken as observation objects. Mueller-Hinton ( MH ) agar , MH blood agar and Brinell agar were used to carried out the drug susceptibility test in vitro, and to compare the results of drug susceptibility test of different medium; the most suitable Brucella drug susceptibility test medium was used to detect the resistance of human derived Brucella to Doxycycline, Rifampicin, Streptomycin, Levofloxacin, Moxifloxacin, Ceftriaxone sodium, Co-trimoxazole and Amoxicillin/Clavulanic acid by K-B drug sensitive paper, and to observe the formation of antibacterial ring around the drug sensitive paper. Results The growth of Brucella on the MH agar and MH blood agar were slower than that on the Brinell agar, and the antibacterial rings were not obvious. All the 180 strains of Brucella were sensitive to seven antibiotics such as Doxycycline, Rifampicin, Streptomycin, Levofloxacin, Moxifloxacin, Ceftriaxone sodium, and Amoxicillin/Clavulanic acid; and 70 strains of Brucella were resistant to Co-trimoxazole, accounting for 39％ (70/180); Brucella strains resistant to Co-trimoxazole were found in 21 provinces. Conclusions Brinell agar is the most suitable medium for Brucella susceptibility test. The human derived Brucella is resistant to Co-trimoxazole; the resistant strains are distributed in 21 provinces ( municipalities , autonomous regions ) . It is recommended that relevant departm ents of the province ( municipalities , autonomous regions ) carry out epidemiological investigations on the resistance of Brucella, and strengthen the monitoring of drug resistance in clinical drugs of brucellosis patients.

Objective Molecular biological methods were used to classify and analyze the isolated Brucella strains,and to understand the geographical distribution characteristics,genetic types and regional distribution characteristics of Brucella in Qinghai Province.Methods Molecular biology typing of species of isolated Brucella strains in Qinghai was studied using Multiple Locus Variable-number tandem repeat Analysis (MLVA) technology.The classification results were described by geographical information system (GIS).Results There were 3 species Brucella melitensis,Brucella abortus,and Brucella suis among the 65 strains of Brucella in Qinghai.Brucella melitensis was the dominant species.The genotypes of MLVA were 42,43,47,28,36,112 and 6.The geographical distribution features showed that the 42 belonged to the evolutionary branches of A and B,which was widely distributed.The 43 of the C evolutionary branch and 47 of the E evolution branch were mainly in the hinterland of the Qinghai-Tibet Plateau.When searching in the Brucella2012 MLVA database,none of the genotypes obtained in this study were identical to those in the database.Conclusions The MLVA genotypes of Brucella are varied in Qinghai Tibet Plateau.They are widely distributed,completely different from those in other areas,and different genetic variations are found in different places.

Objective To investigate the application value of extracorporeal extended field radiotherapy in locally advanced cervical cancer. Methods A total of one hundred and twenty patients with stage IIB?IVA cervical cancer in the First Affiliated Hospital of Hebei North University from June 2012 to June 2014 were randomly divided into two groups:the control group and the observation group,each with 60 cases. The routine concurrent chemoradiotherapy was adopted in the control group. The observation group was treated with extracorporeal extended field radiotherapy combined with concurrent chemotherapy. The patients have been followed up for three years. The total efficacy rate,toxicity reaction,local progression free survival time ( PFS) and survival rate of the two groups were compared. Results The total efficacy rate in the observation group was significantly higher than that of the control group ( 88. 3%( 53/60 ) vs. 73. 3%( 44/60 ) , χ2 = 4. 357, P=0. 037),while the incidences of toxicity reaction in the two groups were 18. 3%(11/60) and 16. 7%(10/60), the difference was not statistically significant (χ2=0. 058,P=0. 810) ,the percentages of I and II degree in the two groups were 3. 4%( 2/60 ) and 3. 4%( 2/60 ) , the difference between the two groups was not statistically significant (Z=0. 000,P=1. 000). The PFS value in the observation group was significantly longer than that of the control group ( 25. 6 months vs. 13. 8 months,χ2 = 25. 624, P= 0. 000 ) , and the survival rate in the observation group improved significantly ( 53. 3%( 32/60 ) vs. 33. 3%( 20/60 ) , the difference was statistically significant (χ2 = 4. 887, P= 0. 027 ) . Conclusion Extracorporeal extended field radiotherapy is safe and effective in the treatment of locally advanced cervical cancer.

Objective To observe the therapeutic effect of Shenluo'an Decoction(SD) for the treatment of obese patients with early diabetic nephropathy and to explore the possible mechanism.Methods A total of 68 obese patients with early diabetic nephropathy were randomly assigned into control group and treatment group,34 cases in each group.Both groups were given conventional western medicine treatment including lifestyle regulation,dietary control,and medicine for lowering blood pressure,blood glucose and blood lipids.Additionally,the control group was given oral use of Irbesartan,and the treatment group was given oral use of SD combined with Irbesartan.Before and after treatment,we observed the traditional Chinese medical syndrome scores,body mass index(BMI),blood levels of cystatin C (Cys C),β2-microglobumin(β2-MG),homocysteine (Hcy) and fasting blood glucose (FBG),and urine parameters of urinary monocyte chemoattractant protein-1 / urinary creatinine (UMCP-1/UCR),urinary factor of regulated on activation in normal T cell expressed and secreted / urinary creatinine (URANTES/UCR),urinary albumin-to-creatinine ratio (UACR) and urinary albumin excretion ratio (UAER) before treatment and after treatment for 16 weeks.After treatment,the clinical efficacy and safety were also evaluated.Results (1) During the treatment,5 cases were dropped out,and a total of 63 cases (32 from the treatment group and 31 from the control group) completed the experiment.(2) The total effective rate of the treatment group(90.6％) was significantly higher than that of the control group(67.7％),the difference being significant(P ＜ 0.05).(3)BMI of the two groups after treatment was significantly lower than that before treatment (P ＜ 0.05).(4) After treatment,the traditional Chinese medical syndrome scores,blood parameters (Cys C,β2-MG,Hcy,FBG) and urine parameters (UMCP-1/UCR,URANTES/UCR,UACR,UAER) in the treatment group were decreased as compared with those before treatment and those in the control group after treatment(P ＜0.05).(5) A positive correlation was present among the parameters of UMCP-1/UCR,URANTES/UCR,UACR and UAER.(6) No abnormal changes took place in the blood and stool routine examination,hepatic function,or electrocardiography of the 63 cases.Conclusion SD combined with western medicine exerts certain therapeutic effect for obese patients with early diabetic nephropathy,and is effective on relieving clinical symptoms anddecreasing BMI,Cys C,β2-MG,UACR,UAER,UMCP-1 and URANTES.Its mechanism is probably related with the inhibition of chronic renal inflammation.

Objective To investigate the chang and impaction of TM and D- Dimer on peripherally inserted central catheter (PICC) associated thrombosis in cancer patients. Methods The expression of TM and D-Dimer from 207 cancer patients with PICC was examined using nzyme-linked immunoassay. Paitents were divided into thrombosis group and control group according to Doppler Sonography. Results The thrombosis group had 33 cases and the control group had 174 cases in 207 malignant tumor patients with PICC. Compared with that in control group, the expression of TM (6.806 ± 1.805)μg/L and D-Dimer (0.786 ± 0.294) mg/L was significantly higher in thrombosis group and respectively statistically significant (P<0.05), The expression of TM and D-Dimer was positively correlated with thrombosis respectively (r=0.572 and 0.530, P<0.05). The multi-factor Logistics analysis showed the odd ratio of TM was 1.899 and the odd ratio of D-Dimer was 7.292, and the difference was statistically significant (P<0.05). Patients were dichotomized into elevated and noneelevated groups according to the 50th percentile of the levels of TM and D-Dimer of the total study population. In multivariable analysis, the odd ratio of both elevated TM and elevated D-Dimer was 2.04, which was higher than elevated TM (1.286) alone and elevated D-Dimer (1.044) alone, and there was difference in statistics (P<0.05). The results showed that the risk of PICC associated with thrombosis in both elevated TM and elevated D-Dimer TM increased 2.042 times. The expression of TM and D-Dimer was correlated with clinical stage respectively (r=0.477 and 0.492, P<0.05);but was not correlated with age, sex, site of tumor and concurrent radiochemotherapy (P>0.05). Conclusions The expression of TM, D-Dimer is elevated, which is expected to assess the early diagnosis and clinical value of PICC associated thrombosis in cancer.

Objective To investigate the level and influencing factors of stigma among patients with lung cancer, in order to provide evidence for staff nurses to take pertinent interventions for assisting patients to deal with stigma. Methods Totally 234 hospitalized patients with lung cancer were cross-sectional survey with General Demographic Questionnaire, Disease Information Questionnaire, Chinese version of Cataldo Lung Cancer Stigma Scale (CLCSS-CV). Results The total score of stigma was (72.35±10.85) points. The total scale score and each subscale score was divided by the item number. The mean score of CLCSS-CV was (2.68±0.40) points, the rate of the patients with lung cancer with moderate above stigma was 51.20% (120/234). The patients rated higher scores on the subscales of smoking (2.90±0.58) points, while lower scores on the subscales of discrimination (2.47 ±0.55) points. Multiple stepwise regression analysis showed that the number of children and the clinical stages were influencing factors of lung cancer stigma, where regression coefficients were -0.065, 0.136 respectively, coefficients of determination was 0.178. Conclusions Patients with lung cancer have a moderate or higher level of stigma. The medical staff should communicate with patients, evaluate the psychological status, impose public health education, mobilize the social support for assisting them to deal with stigma.

Objective To evaluated the effectiveness and safety ofLianhua Jizhi Tablets for acute trachitis and bronchitis with syndrome of phlegm-heat obstructing.Methods A randomized double-blind, placebo-controlled and multi-center clinical trial design was selected. Totally 240 cases were randomly divided into experimental group and control group, 120 cases in each group, of which 237 cases were included in the analysis of FAS. Experimental group was givenLianhua Jizhi Tablets, while control group was given placebo, 12 tablets/day, 7 days for a course. Curative effect of acute trachitis and bronchitis, TCM syndrome and disappearance of cough, cough and sputum symptom scores and area under the curve (AUC) were observed. The safety was evaluated. Results The cure rates of disease in experimental group and control group were 66.67% (78/117) and 29.17% (35/120), respectively;cure rates of TCM syndrome in experimental group and the control group were 68.38% (80/117) and 27.50% (33/120), respectively;there was statistically significant difference in area under the curve of cough and sputum symptom score between the two groups (P<0.01). Disappearance rates (cure) of daytime cough in experimental group and control group were 52.99% (62/117) and 13.33% (16/120), respectively;disappearance rates (cure) of nocturnal cough in experimental group and control group were 76.52% (88/115) and 31.90% (37/116), respectively;there were no side effects in experimental group.ConclusionLianhua Jizhi Tablets can significantly relieve clinic symptoms in the treatment of acute trachitis and bronchitis, and have good clinical efficacy and safety.