Objective To systematically evaluate the therapeutic effects of different surgical procedures for ischemic mitral regurgitation (IMR). Methods Computer searches were conducted in CNKI, Wanfang, VIP, CBM, PubMed, Cochrane Library, Embase, and Web of Science, with the search time limit from the inception of the databases to February 2024. Two researchers independently screened the literature, extracted data, used the Cochrane bias risk assessment tool to evaluate the quality of the included studies, and used Stata 17.0 software to analyze the data. Results A total of 19 randomized controlled trials involving 6139 patients were finally included, involving six surgical procedures, and the overall quality of the included studies was relatively high. The results of the network meta-analysis showed that the 30-day all-cause mortality rate of mitral valve repair (MVr) was significantly lower than that of coronary artery bypass grafting (CABG) [OR=0.24, 95%CI (0.07, 0.87), P<0.01], mitral valve replacement (MVR) [OR=0.43, 95%CI (0.23, 0.79), P=0.02], CABG+MVR [OR=0.21, 95%CI (0.04, 0.95), P=0.03] and transcatheter mitral valve edge-to-edge repair (TEER) using MitraClip [OR=0.13, 95%CI (0.02, 0.87), P<0.01]. The 30-day all-cause mortality rate of CABG+MVr was significantly lower than that of CABG [OR=0.56, 95%CI (0.33, 0.93), P=0.02] and CABG+MVR [OR=0.48, 95%CI (0.24, 0.94), P=0.04], and the best probability ranking results showed that MVR might be the most effective in reducing the 30-day all-cause mortality rate. The incidence of renal complications in CABG+MVr was significantly lower than that in CABG+MVR [OR=0.42, 95%CI (0.21, 0.83), P=0.01]; the best probability ranking results showed that CABG+MVr might be the most effective in reducing renal complications. Conclusion The current limited evidence suggests that CABG+MVr and MVr may be the best surgical intervention methods for IMR patients at present. Due to the limitations of the number and quality of included studies, the above conclusions still need to be verified by more high-quality studies.

Objective To systematically evaluate the differences in outcomes between functional mitral regurgitation (FMR) and degenerative mitral regurgitation (DMR) in patients treated with transcatheter edge-to-edge repair (TEER) using the MitraClip device. Methods A systematic literature search was conducted in PubMed, Embase, the Cochrane Library, Web of Science, the CNKI, Wanfang Database, VIP Database, and the CBM from their inception to January 2024. Two researchers independently performed study selection, data extraction, and risk of bias assessment. The quality of cohort studies was evaluated using the Newcastle-Ottawa Scale (NOS). A meta-analysis was performed using Stata 18.0 software. Results A total of 13 cohort studies involving 6 402 patients were included, comprising 4 161 patients in the FMR group and 2 241 in the DMR group. All included studies had NOS scores of ≥6 points. The meta-analysis revealed that compared to the DMR group, the FMR group had a higher 1-year all-cause mortality rate [OR=1.53, 95%CI (1.30, 1.81), P＜0.01] and a higher 1-year rehospitalization rate for heart failure [OR=1.90, 95%CI (1.60, 2.26), P＜0.01]. Conversely, the FMR group had a lower post-procedural mean transmitral gradient [SMD=–0.47, 95%CI (–0.65, –0.30), P＜0.01] and a lower rate of subsequent mitral valve surgery [OR=0.41, 95%CI (0.20, 0.83), P=0.01]. Conclusion Following MitraClip therapy, patients with FMR exhibit favorable short-term outcomes, but their mid- to long-term outcomes are inferior to those of patients with DMR. When determining the treatment strategy with MitraClip, the specific etiology of mitral regurgitation should be considered for a more accurate prediction of therapeutic efficacy and prognosis.

Objective:To explore the effect of levonorgestrel-releasing intrauterine system (LNG-IUS) placed in the uterine cavity after transcervical preparation for the treatment of adenomyosis (AM).Methods:A retrospective study analyzed 219 cases of AM patients treated at Department of Obstetrics and Gynaecology, the Second Hospital of Hebei Medical University from March 2022 to February 2023. Among them, 112 cases were treated with LNG-IUS after hysteroscopy due to abnormal uterine bleeding or abnormal uterine echo suggested by gynecological ultrasound, and were recorded as the hysteroscopy+LNG-IUS group; 107 cases without the above manifestations were treated with LNG-IUS alone, and were recorded as the LNG-IUS group. The two groups were observed for dysmenorrhea severity, menstrual volume, endometrial thickness, anemia, serum CA125 levels, uterine volume, and adverse reactions such as abnormal vaginal bleeding and intrauterine contraceptive device displacement or shedding before and 1, 3, 6, and 12 months after treatment.Results:1) Postoperative pathology of hysteroscopy+LNG-IUS group after hysteroscopy included endometrial polyps [39.3% (44/112)], proliferative endometrium [16.1% (18/112)], uterine leiomyoma [11.6% (13/112)], secretory endometrium [8.9% (10/112)], irregular endometrial hyperplasia [6.2% (7/112)], simple hyperplasia [5.4% (6/112)], AM lesions [4.5% (5/112)], and others [8.0% (9/112)]. 2) The degree of dysmenorrhea and menstrual volume, as well as other indicators, improved after treatment in both groups (all P<0.001). 3) When comparing the two groups, the degree of dysmenorrhea, menstrual volume, endometrial thickness, anemia, and serum CA125 at 1, 3, 6, and 12 months of treatment, the hysteroscopy+LNG-IUS group was significantly better than those in the LNG-IUS group (all P<0.05), the difference of uterine volume at 12 months of treatment between the hysteroscopy+LNG-IUS group [(109.76±32.90) cm 3] and the LNG-IUS group [(120.84±31.30) cm 3] was statistically significant ( P=0.011). 4) The cumulative incidence of adverse reactions of the two groups was statistically significant ( P=0.001) between the hysteroscopy+LNG-IUS group [24.1% (27/112)] and the LNG-IUS group [52.3% (56/107), P=0.001]. The hysteroscopy+LNG-IUS group had lower rates of vaginal irregular bleeding [8.0% (9/112)] and ring displacement or shedding [3.6% (4/112)] than those in the LNG-IUS group [23.4% (25/107), P=0.002; 11.2% (12/107), P=0.030]. Conclusion:After treatment with hysteroscopy, the placement of LNG-IUS and the simple intrauterine placement of LNG-IUS both significantly improve the severity of dysmenorrhea, endometrial thickness, anemia, menstrual volume, CA125, and uterine volume. The treatment effect of the LNG-IUS group after hysteroscopy is better and adverse reactions are milder, and it is expected to become the preferred option for the long-term management of conservative treatment of AM.

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.

This study investigated the therapeutic effects of a low-dose phage cocktail combined with antibiotics on burn wounds in-fected with multidrug resistant Pseudomonas aeruginosa.Given the risk of sepsis caused by drug-resistant bacteria infection after burns and the limitations of antibiotic monotherapy,we constructed a mouse model of burns combined with Pseudomonas aeruginosa infection.A saline control group,phage cocktail monotherapy group,antibiotic monotherapy group,and combined treatment group were examined.The combined treatment group showed a synergistic effect on the 7th day after infection:this group of mice had a sig-nificantly lower pathogenic bacterial load in the skin and liver tissues than observed in the single drug treatment group,and showed the strongest bacterial clearance effect.Histopathological analysis indicated improved structural integrity of the skin tissue,as well as decreased infiltration of inflammatory cells,and no obvious tissue damage,in the combined treatment group.Detection of serum in-flammatory factors indicated that the levels of the pro-inflammatory factors IL-6 and TNF-α significantly decreased,whereas the level of anti-inflammatory factor IL-10 significantly increased.The combination of low-dose phage cocktail and antibiotics synergistically en-hanced antibacterial activity and ameliorated infection through a dual mechanism of direct removal of pathogens and regulation of the host immune response.Our findings provide an experimental basis for the optimal treatment of wounds infected with multidrug-resistant bacteria.

Objective:To explore the effect of levonorgestrel-releasing intrauterine system (LNG-IUS) placed in the uterine cavity after transcervical preparation for the treatment of adenomyosis (AM).Methods:A retrospective study analyzed 219 cases of AM patients treated at Department of Obstetrics and Gynaecology, the Second Hospital of Hebei Medical University from March 2022 to February 2023. Among them, 112 cases were treated with LNG-IUS after hysteroscopy due to abnormal uterine bleeding or abnormal uterine echo suggested by gynecological ultrasound, and were recorded as the hysteroscopy+LNG-IUS group; 107 cases without the above manifestations were treated with LNG-IUS alone, and were recorded as the LNG-IUS group. The two groups were observed for dysmenorrhea severity, menstrual volume, endometrial thickness, anemia, serum CA125 levels, uterine volume, and adverse reactions such as abnormal vaginal bleeding and intrauterine contraceptive device displacement or shedding before and 1, 3, 6, and 12 months after treatment.Results:1) Postoperative pathology of hysteroscopy+LNG-IUS group after hysteroscopy included endometrial polyps [39.3% (44/112)], proliferative endometrium [16.1% (18/112)], uterine leiomyoma [11.6% (13/112)], secretory endometrium [8.9% (10/112)], irregular endometrial hyperplasia [6.2% (7/112)], simple hyperplasia [5.4% (6/112)], AM lesions [4.5% (5/112)], and others [8.0% (9/112)]. 2) The degree of dysmenorrhea and menstrual volume, as well as other indicators, improved after treatment in both groups (all P<0.001). 3) When comparing the two groups, the degree of dysmenorrhea, menstrual volume, endometrial thickness, anemia, and serum CA125 at 1, 3, 6, and 12 months of treatment, the hysteroscopy+LNG-IUS group was significantly better than those in the LNG-IUS group (all P<0.05), the difference of uterine volume at 12 months of treatment between the hysteroscopy+LNG-IUS group [(109.76±32.90) cm 3] and the LNG-IUS group [(120.84±31.30) cm 3] was statistically significant ( P=0.011). 4) The cumulative incidence of adverse reactions of the two groups was statistically significant ( P=0.001) between the hysteroscopy+LNG-IUS group [24.1% (27/112)] and the LNG-IUS group [52.3% (56/107), P=0.001]. The hysteroscopy+LNG-IUS group had lower rates of vaginal irregular bleeding [8.0% (9/112)] and ring displacement or shedding [3.6% (4/112)] than those in the LNG-IUS group [23.4% (25/107), P=0.002; 11.2% (12/107), P=0.030]. Conclusion:After treatment with hysteroscopy, the placement of LNG-IUS and the simple intrauterine placement of LNG-IUS both significantly improve the severity of dysmenorrhea, endometrial thickness, anemia, menstrual volume, CA125, and uterine volume. The treatment effect of the LNG-IUS group after hysteroscopy is better and adverse reactions are milder, and it is expected to become the preferred option for the long-term management of conservative treatment of AM.

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

This study investigated the therapeutic effects of a low-dose phage cocktail combined with antibiotics on burn wounds in-fected with multidrug resistant Pseudomonas aeruginosa.Given the risk of sepsis caused by drug-resistant bacteria infection after burns and the limitations of antibiotic monotherapy,we constructed a mouse model of burns combined with Pseudomonas aeruginosa infection.A saline control group,phage cocktail monotherapy group,antibiotic monotherapy group,and combined treatment group were examined.The combined treatment group showed a synergistic effect on the 7th day after infection:this group of mice had a sig-nificantly lower pathogenic bacterial load in the skin and liver tissues than observed in the single drug treatment group,and showed the strongest bacterial clearance effect.Histopathological analysis indicated improved structural integrity of the skin tissue,as well as decreased infiltration of inflammatory cells,and no obvious tissue damage,in the combined treatment group.Detection of serum in-flammatory factors indicated that the levels of the pro-inflammatory factors IL-6 and TNF-α significantly decreased,whereas the level of anti-inflammatory factor IL-10 significantly increased.The combination of low-dose phage cocktail and antibiotics synergistically en-hanced antibacterial activity and ameliorated infection through a dual mechanism of direct removal of pathogens and regulation of the host immune response.Our findings provide an experimental basis for the optimal treatment of wounds infected with multidrug-resistant bacteria.

Objective:To compare the safety and efficacy of transarterial chemoembolization (TACE) combined with donafenib and programmed death protein 1 (PD-1) inhibitors and TACE combined with donafenib in the treatment of unresectable hepatocellular carcinoma (uHCC).Methods:Clinical data of 148 patients with uHCC treated at the First Affiliated Hospital of Zhengzhou University from December 2021 to December 2022 were retrospectively analyzed, including 127 males and 21 females, aged (56.6±9.9) years. Patients were divided into two groups: the TACE combined with donafenib and PD-1 inhibitors group (TACE+ DP, n=73) and TACE combined with single donafenib (TACE+ D, n=75). The overall survival (OS), progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR), and the occurrence of treatment-related adverse events (TRAEs) of the two groups of patients were observed. Kaplan-Meier analysis was used for survival assessment, and the log-rank test was used for comparison. The related factors affecting the prognosis of patients were indentified and analyzed. Results:The median PFS of patients in the TACE+ D group and the TACE+ DP group were 7.2 months (95% CI: 5.7-8.3 months) and 10.5months (95% CI: 8.9-11.3 months), respectively. The median OS was 13.2 months (95% CI: 12.3-13.7 months) and 16.9 months (95% CI: 15.1-19.8 months), respectively. All these differences were statistically significant ( χ2=17.81, 26.92, respectively, both P<0.001). The ORR and DCR of TACE+ DP group were both higher than those in TACE+ D group [53.4% (39/73) vs 36.0% (27/75), χ2=4.55, P=0.031; and 90.4% (66/73) vs 77.3% (58/75), χ2=4.66, P=0.044]. No grade 4 or above adverse events occurred in either the TACE+ DP or the TACE+ D group. The most common treatment-related adverse events in TACE+ D and TACE+ DP group were hand-foot syndrome [46.7% (35/75) vs 49.3% (36/73)], hypertension [26.7% (20/75) vs 30.1% (22/73)], fatigue [22.7% (17/75) vs 24.7% (18/73)], diarrhea [26.7% (20/75) vs 28.8% (21/73)], and thrombocytopenia [25.3% (19/75) vs 28.8% (21/73)]. There was no significant difference in the incidence and severity of TRAEs between the groups ( χ2=0.08, P=0.774). TACE+ DP treatment was a favorable prognostic factor for PFS ( HR=0.33, 95% CI: 0.22-0.49, P<0.001) and OS ( HR=0.19, 95% CI: 0.11-0.33, P<0.001) of patients. Conclusion:Compared to TACE combined with donafenib, TACE combined with donafenib and PD-1 inhibitors, with good efficacy and safety, significantly improved the treatment response and survival in patients with uHCC.

Cervical spinal cord injury without fracture-dislocation (CSCIWFD) is referred to as a special type of cervical spinal cord injury characterized by traumatic spinal cord dysfunction and no significant bony structural abnormalities on imagines. Duo to the high risk of missed diagnosis during the initial consultation, CSCIWFD may lead to progressive neurological deterioration or even complete paralysis, severely impacting patients′ prognosis. Currently, there are no established consensuses over the diagnosis and treatment of CSCIWFD, such as the lack of evidence-based standards for indications of non-surgical treatment and risk of secondary neurological injury, as well as debates over the optimal timing for surgical intervention and indications for different surgical approaches. To address these issues, the Spine Trauma Group of the Orthopedic Branch of the Chinese Medical Doctor Association organized experts in the relevant fields to formulate Diagnosis and treatment guideline for acute cervical spinal cord injury without fracture- dislocation in adults ( version 2025) . Based on evidence-based medicine and the principles of scientific rigor and clinical applicability, the guidelines proposed 11 recommendations covering terminology, diagnosis, evaluation treatment, and rehabilitation, etc., aiming to standardize the management of CSCIWFD.