Deep learning model based on endoscopic images predicting treatment response in locally advanced rectal cancer undergo neoadjuvant chemoradiotherapy: a multicenter study.

PURPOSE: Neoadjuvant chemoradiotherapy has been the standard practice for patients with locally advanced rectal cancer. However, the treatment response varies greatly among individuals, how to select the optimal candidates for neoadjuvant chemoradiotherapy is crucial. This study aimed to develop an endoscopic image-based deep learning model for predicting the response to neoadjuvant chemoradiotherapy in locally advanced rectal cancer. METHODS: In this multicenter observational study, pre-treatment endoscopic images of patients from two Chinese medical centers were retrospectively obtained and a deep learning-based tumor regression model was constructed. Treatment response was evaluated based on the tumor regression grade and was defined as good response and non-good response. The prediction performance of the deep learning model was evaluated in the internal and external test sets. The main outcome was the accuracy of the treatment prediction model, measured by the AUC and accuracy. RESULTS: This deep learning model achieved favorable prediction performance. In the internal test set, the AUC and accuracy were 0.867 (95% CI: 0.847-0.941) and 0.836 (95% CI: 0.818-0.896), respectively. The prediction performance was fully validated in the external test set, and the model had an AUC of 0.758 (95% CI: 0.724-0.834) and an accuracy of 0.807 (95% CI: 0.774-0.843). CONCLUSION: The deep learning model based on endoscopic images demonstrated exceptional predictive power for neoadjuvant treatment response, highlighting its potential for guiding personalized therapy.

Mechanism of Mutation-Induced Effects on the Catalytic Function of TEV Protease: A Molecular Dynamics Study.

Tobacco etch virus protease (TEVp) is wildly exploited for various biotechnological applications. These applications take advantage of TEVp's ability to cleave specific substrate sequences to study protein function and interactions. A major limitation of this enzyme is its relatively slow catalytic rate. In this study, MD simulations were conducted on TEV enzymes and known highly active mutants (eTEV and uTEV3) to explore the relationship between mutation, conformation, and catalytic function. The results suggest that mutations distant from the active site can influence the substrate-binding pocket through interaction networks. MD analysis of eTEV demonstrates that, by stabilizing the orientation of the substrate at the catalytic site, mutations that appropriately enlarge the substrate-binding pocket will be beneficial for Kcat, enhancing the catalytic efficiency of the enzyme. On the contrary, mutations in uTEV3 reduced the flexibility of the active pocket and increased the hydrogen bonding between the substrate and enzyme, resulting in higher affinity. At the same time, the MD simulation demonstrates that mutations outside of the active site residues could affect the dynamic movement of the binding pocket by altering residue networks and communication pathways, thereby having a profound impact on reactivity. These findings not only provide a molecular mechanistic explanation for the excellent mutants, but also serve as a guiding framework for rational computational design.

Application of Novel Azetidinium Cationic Polyurethane Dispersion Finishing Agent for Wool Fabrics.

Machine-washable and antimicrobial substances are the demand for the current wool fabrics. The characteristic of wool fabric is studied with novel self-made azetidinium cationic polyurethane dispersions (PUDs), which used dihydroxyalkyl glycidylamine as the chain extender. Dihydroxyalkyl glycidylamine was synthesized by ring opening with epichlorohydrin and diisopropanolamine. Influences of the cationic PUDs on antibacterial properties, felting shrinkage, and yellowness index of wool fabric are studied. The results show that the antifelting feature of wool fabric with the cationic PUDs is better than the others. It is also found that the wool fabric has a clear antibacterial property. The optimal process has been concluded as follows: the compound PUDs of 50 g/L and curing at 130 °C 5.0 min. The finished fabric has low felting shrinkage after washing for 20 times at 60 °C.

Labor epidural analgesia versus without labor epidural analgesia for multiparous women: a retrospective case control study.

BACKGROUND: Labor epidural analgesia (LEA) effectively relieves the labor pain, but it is still not available consistently for multiparous women in many institutions because of their obviously shortened labor length. METHODS: A total of 811 multiprous women were retrospective enrolled and firstly divided into two groups: LEA group or non-LEA group. And then they were divided into seven subgroups and analyzed according to the use of LEA and cervical dilation. The primary outcomes (time intervals, blood loss and Apgar scores) and secondary outcomes (maternal demographic characteristics and birth weight) were collected by checking electronic medical records. RESULTS: The prevalence of using LEA in multiprous women was 54.5 %. Using LEA significantly lengthened the duration of labor stage by 56 min (P < 0.001), increased the blood loss (P < 0.001) and lowered Apgar scores (P = 0.001). In the comparison of sub-group analysis, using LEA can obviously prolong the duration of first-second stage in women with 2 cm cervical dilation (P < 0.001) and 3 cm cervical dilation (P = 0.014), while there was no significant difference with 4 cm or more cervical dilation (P = 0.69). Using LEA can significantly increased the blood loss when the initiation of LEA in the women with 2 cm cervical dilation (P < 0.001) and 3 cm cervical dilation (P = 0.035), meanwhile there were no significantly differences in the women with 4 cm or more cervical dilation (P = 0.524). Using LEA can significantly lower the Apgar scores when the initiation of LEA in the women with 2 cm cervical dilation (P = 0.001) and 4 cm or more cervical dilation (P = 0.025), while there were no significantly differences in the women with 3 cm cervical dilation (P = 0.839). CONCLUSIONS: Labor epidural analgesia for the multiparous woman may alter progress of labor, increase postpartum blood loss and lower Apgar scores. Early or late initiation of LEA should be defined as with cervical dilatation of less or more than 3 cm and the different effect should be understand. TRIAL REGISTRATION: ChiCTR2100042746. Registered 27 January 2021-Prospectively registered, http://www.chictr.org.cn .

[Expression of intercellular adhesion molecule-1 and vascular cell adhesion molecule in cardiac allografts and significance thereof: experiment with rats].

OBJECTIVE: To investigate the expression of intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) in allograft with chronic rejection (CR) after heart transplantation. METHODS: Seventy-two SD rats receiving transplantation of the heats of 71 Wistar rats were divided into 4 equal groups: Group A, undergoing heterotopic cervical heart transplantation (transplanted with donor's heart subcutaneously at the neck) and receiving none intervention, and with the transplanted hearts taken out 3 d after transplantation to the end of CR; Group B, injected intravenously with the splenocytes (SPCs) of the donors on day 0, injected with cyclophomide (CP) on d2, transplanted with the donor hearts on d15, with the transplanted hearts taken out 15 - 120 days after transplantation; Group C, transplanted with the donor's heart and injected intraperitoneally with cyclosporine A (Cs A) 10 mg/kg every other day for 8 - 10 times, and with the transplanted hearts taken out 60 d after transplantation to the end of CR; and Group D, injected intravenously with the SPCs of the donors on day 0, injected with CP on d2, transplanted with the donor hearts on d15, with the transplanted hearts taken out 150 - 420 days after transplantation. Immunohistochemical method was used to detect the expression of ICAM-1 and VCAM-1 in the allografts. RESULTS: The cardiac allograft survival time of Group B was the longest. Less ICAM-1 and VCAM-1 expression and lymphocyte infiltration were observed in SPC and CP-pretreated group. Reversely, protein expression levels of ICAM-1 and VCAM-1 were both high and significant lymphocyte infiltration was seen in Groups B and D. There was no significant difference in the expression of ICAM-1 and VCAM-1 between Groups A and C (P > 0.05). CONCLUSION: The expression levels of ICAM-1 and VCAM-1 are associated with the occurrence and development of rejection and have positive correlation with the severity of graft rejection. Determination of ICAM-1 and VCAM-1 can predict the function of allograft and provide evidence for early diagnosis and prevention of CR.