Exploring vision transformers for classifying early Barrett's dysplasia in endoscopic images: A pilot study on white-light and narrow-band imaging.

Background and Aim: Various deep learning models, based on convolutional neural network (CNN), have been shown to improve the detection of early esophageal neoplasia in Barrett's esophagus. Vision transformer (ViT), derived from natural language processing, has emerged as the new state-of-the-art for image recognition, outperforming predecessors such as CNN. This pilot study explores the use of ViT to classify the presence or absence of early esophageal neoplasia in endoscopic images of Barrett's esophagus. Methods: A BO dataset of 1918 images of Barrett's esophagus from 267 unique patients was used. The images were classified as dysplastic (D-BO) or non-dysplastic (ND-BO). A pretrained vision transformer model, ViTBase16, was used to develop our classifier models. Three ViT models were developed for comparison based on imaging modality: white-light imaging (WLI), narrow-band imaging (NBI), and combined modalities. Performance of each model was evaluated based on accuracy, sensitivity, specificity, confusion matrices, and receiver operating characteristic curves. Results: The ViT models demonstrated the following performance: WLI-ViT (Accuracy: 92%, Sensitivity: 82%, Specificity: 95%), NBI-ViT (Accuracy: 99%, Sensitivity: 97%, Specificity: 99%), and combined modalities-ViT (Accuracy: 93%, Sensitivity: 87%, Specificity: 95%). Combined modalities-ViT showed greater accuracy (94% vs 90%) and sensitivity (80% vs 70%) compared with WLI-ViT when classifying WLI images on a subgroup testing set. Conclusion: ViT exhibited high accuracy in classifying the presence or absence of EON in endoscopic images of Barrett's esophagus. ViT has the potential to be widely applicable to other endoscopic diagnoses of gastrointestinal diseases.

[A multicenter study on effect of delayed chemotherapy on prognosis of Burkitt lymphoma in children].

Objective: To analyze the factors affecting delayed chemotherapy in children with Burkitt lymphoma (BL) and their influence on prognosis. Methods: Retrospective cohort study. Clinical data of 591 children aged ≤18 years with BL from May 2017 to December 2022 in China Net Childhood Lymphoma (CNCL) was collected. The patients were treated according to the protocol CNCL-BL-2017. According to the clinical characteristics, therapeutic regimen was divided into group A, group B and group C .Based on whether the total chemotherapy time was delayed, patients were divided into two groups: the delayed chemotherapy group and the non-delayed chemotherapy group. Based on the total delayed time of chemotherapy, patients in group C were divided into non-delayed chemotherapy group, 1-7 days delayed group and more than 7 days delayed group. Relationships between delayed chemotherapy and gender, age, tumor lysis syndrome before chemotherapy, bone marrow involvement, disease group (B/C group), serum lactate dehydrogenase (LDH) > 4 times than normal, grade Ⅲ-Ⅳ myelosuppression after chemotherapy, minimal residual disease in the interim assessment, and severe infection (including severe pneumonia, sepsis, meningitis, chickenpox, etc.) were analyzed. Logistic analysis was used to identify the relevant factors. Kaplan-Meier method was used to analyze the patients' survival information. Log-Rank was used for comparison between groups. Results: Among 591 patients, 504 were males and 87 were females, the follow-up time was 34.8 (18.6,50.1) months. The 3-year overall survival (OS) rate was (92.5±1.1)%,and the 3-year event-free survival (EFS) rate was (90.5±1.2)%. Seventy-three (12.4%) patients were in delayed chemotherapy group and 518 (87.6%) patients were in non-delayed chemotherapy group. The reasons for chemotherapy delay included 72 cases (98.6%) of severe infection, 65 cases (89.0%) of bone marrow suppression, 35 cases (47.9%) of organ dysfunction, 22 cases (30.1%) of tumor lysis syndrome,etc. There were 7 cases of chemotherapy delay in group B, which were seen in COPADM (vincristine+cyclophosphamide+prednisone+daunorubicin+methotrexate+intrathecal injection,4 cases) and CYM (methotrexate+cytarabine+intrathecal injection,3 cases) stages. There were 66 cases of chemotherapy delay in group C, which were common in COPADM (28 cases) and CYVE 1 (low dose cytarabine+high dose cytarabine+etoposide+methotrexate, 12 cases) stages. Multinomial Logistic regression analysis showed that the age over 10 years old (OR=0.54,95%CI 0.30-0.93), tumor lysis syndrome before chemotherapy (OR=0.48,95%CI 0.27-0.84) and grade Ⅲ-Ⅳ myelosuppression after chemotherapy (OR=0.55,95%CI 0.33-0.91)were independent risk factors for chemotherapy delay.The 3-year OS rate and the 3-year EFS rate of children with Burkitt lymphoma in the delayed chemotherapy group were lower than those in the non-delayed chemotherapy group ((79.4±4.9)% vs. (94.2±1.1)%, (80.2±4.8)% vs. (92.0±1.2)%,both P<0.05). The 3-year OS rate of the group C with chemotherapy delay >7 days (42 cases) was lower than that of the group with chemotherapy delay of 1-7 days (22 cases) and the non-delay group (399 cases) ((76.7±6.9)% vs. (81.8±8.2)% vs. (92.7±1.3)%, P=0.002).The 3-year OS rate of the chemotherapy delay group (9 cases) in the COP (vincristine+cyclophosphamide+prednisone) phase was lower than that of the non-chemotherapy delay group (454 cases) ((66.7±15.7)% vs. (91.3±1.4)%, P=0.005). Similarly, the 3-year OS rate of the chemotherapy delay group (11 cases) in the COPADM1 phase was lower than that of the non-chemotherapy delay group (452 cases) ((63.6±14.5)% vs. (91.5±1.3)%, P=0.001). Conclusions: The delayed chemotherapy was related to the age over 10 years old, tumor lysis syndrome before chemotherapy and grade Ⅲ-Ⅳ myelosuppression after chemotherapy in pediatric BL. There is a significant relationship between delayed chemotherapy and prognosis of BL in children.

[Analysis of virus gene subtypes and drug resistance monitoring results of newly reported HIV/AIDS population in Anhui Province from 2020 to 2023].

Objective: To investigate the genetic subtypes and drug resistance monitoring of newly reported human immunodeficiency virus (HIV) infection/AIDS virus in Anhui Province from 2020 to 2023. Methods: An observational design study was used to collect blood samples from patients diagnosed with HIV/AIDS in the AIDS Prevention and Control Department of Anhui Provincial Center for Disease Control and Prevention from January 2020 to December 2023.The HIV-1 pol gene was amplified by reverse transcription-nested PCR, and the genetic subtypes were identified by phylogenetic tree analysis using MEGA 7.0 software. The mutation sites of drug resistance were analyzed by the online software tool of Stanford University's HIV Drug resistance database. The influencing factors of drug resistance before treatment were analyzed by multivariate logistic analysis. Results: A total of 335 plasma samples were collected, and 332 HIV-1 pol gene sequences were obtained successfully. The main gene subtypes were CRF01-AE, accounting for 35.55% (118/332), followed by CRF07-BC, B and B+C types [29.22% (97/332), 11.74% (39/332), 9.93% (33/332)]. The total drug resistance rate before treatment was 30.12%(32/100), and the drug resistance rate of protease inhibitor (PIs) in HIV-1 was 6.33% (21/332). The drug resistance rate of nucleoside reverse transcriptase inhibitors (NRTI) before treatment was 6.33% (21/332). The drug resistance rate of non-nucleoside reverse transcriptase inhibitors (NNRTI) before treatment was 17.47% (58/332).The comparison of drug resistance rate of different drug types showed statistical significance (χ2=30.435, P<0.05).Among the 100 cases of drug resistance, the main mutation point of HIV-1 protease inhibitor was Q58E (21.00%), and the main mutation point of nucleoside reverse transcriptase inhibitor was M184V/I (6.00%). Non-nucleoside reverse transcriptase inhibitor resistance mutation points mainly K103N (22.00%).There were statistically significant differences in the starting time of antiviral therapy, the number of CD4+T cells at baseline and the drug resistance rate of gene subtypes (the chi-square values are respectively 24.152, 32.516, 11.652, P<0.05).Multivariate logistic analysis showed that the baseline CD4+T cell count was <200/µl, subtype B, subtype B+C, CRF01-AE subtype, CRF55-01B subtype and 01-BC subtype was the influential factor of drug resistance before treatment (the chi-square values are respectively 4.577, 8.202, 4.416, 5.206, 7.603 and 4.804, P<0.05). Conclusion: The newly reported HIV/AIDS population in Anhui Province from 2020 to 2023 has a variety of viral gene subtypes, and NNRTIs are the main types of drug resistance gene mutations before treatment. Attention should be paid to the number of baseline CD4+T cells, the duration of antiviral treatment, and the distribution of gene subtypes to reduce the drug resistance of HIV/AIDS patients before treatment.

A risk-prediction score about colorectal lesions based on the Chinese population of high-risk participants aged 50-65 years.

OBJECTIVES: The present study aims to develop an effective risk-prediction score (RPS) to improve screening efficiency and contribute to secondary prevention of colorectal cancer (CRC). STUDY DESIGN: Screening for colorectal lesions. METHODS: 14,398 high-risk individuals aged 50-65 years were included. The baseline characteristics of participants with and without colorectal lesions (CL) were compared using a Chi-squared test. The overall population was randomly split into a training set and a test set in the ratio of 80% and 20%. One-factor and multifactor logistic regression analyses were performed in the training set to construct the RPS (scores of 0-9.62). Area under curve (AUC) was calculated as an estimate of predictive performance using the receiver-operating characteristic (ROC) curve in the test set. RESULTS: In the study population, being male, advanced age, current or previous smoking, weekly alcohol consumption, high body mass index (BMI ≥24 kg/m2), and previously detected colonic polyp were associated with higher risk of CL. Compared to the low-risk group (0-2.31 points), the ORs and 95% confidence intervals (CIs) for the moderate-risk group (2.31-3.85 points) and high-risk group (3.85-8.42 points) were 1.58 (1.44, 1.73) and 2.52 (2.30, 2.76), respectively. For every 1-point increase in score, participants had a 27% increased risk of CL (OR:1.27, 95% CI: 1.24, 1.30). For participants with CL predicted by RPS, the area under the working characteristic curve was 0.61 (P < 0.001). CONCLUSION: Our RPS can quickly and efficiently identify multiple lesions of the colorectum. Combining RPS with existing screening strategies facilitates the identification of very high-risk individuals and may help to prevent CRC.

[Clinical features and outcomes of digestive tract perforation in pediatric mature B-cell non-Hodgkin lymphoma].

To summarize the clinical features and prognosis of pediatric mature B-cell non-Hodgkin lymphoma (mB-NHL) with digestive tract perforation. The clinical manifestations, laboratory and imaging examinations, treatment and outcomes of mB-NHL children complicated with digestive tract perforation admitted to Beijing Children's Hospital of Capital Medical University from January 2016 to June 2023 were retrospectively analyzed. A total of 12 patients were included, with 11 males and 1 female, aged 0.8-16.0 (7.5±5.4) years. Among them, there were 10 cases of Burkitt lymphoma, 1 case of high-grade B-cell lymphoma (HGBL) and 1 case of diffuse large B-cell lymphoma (DLBCL), respectively. Intestinal involvement was involved in all cases, with St.Jude staging ranging from stage Ⅲ to Ⅳ. Eleven cases had large abdominal mass. In 7 cases, abdominal X-ray examination showed free gas under the diaphragm. Eleven cases experienced digestive tract perforation after chemotherapy, and the time of perforation after initiation of chemotherapy was 2.0-111.0 (41.2±33.6) days. The most common site of perforation was ileum (6 cases), followed by gastric wall (2 cases), jejunum (1 case), colon (1 case) and appendix (1 case). Eight patients underwent surgery, and the time between surgery and re-chemotherapy was 7.0-45.0 (17.6±12.0) days. One case with perforation before chemotherapy died after giving up treatment. The remaining 11 cases received conservative treatment or surgical intervention, followed by regular chemotherapy after symptom and infection control. The follow-up time was 6.0-82.0 (45.0±26.1) months, and all survived.

[Interim efficacy of a multicenter cohort study for China Net Childhood Lymphoma mature B-cell lymphoma 2017 regimen in the treatment of pediatric High-grade-B cell lymphoma].

Objective: To analyze the mid-term efficacy of the China Net Childhood Lymphoma mature B-cell lymphoma 2017 (CNCL-B-NHL-2017) regimen in treating children with high-grade B-cell lymphoma (HGBL). Methods: Clinical and pathological data of HGBL children aged≤18 years admitted to 16 hospitals of the Chinese Children's Lymphoma Collaborative Group (CNCL) from May 2017 to April 2021 were collected retrospectively. They were divided in to high-grade B-cell lymphoma with double hit/triple hit (HGBL-DH/TH) group and high-grade B-cell lymphoma non-specified (HGBL-NOS) group, according to the 2016 version of the World Health Organization (WHO) Hematopoietic and Lymphoid Tissues Cancer Classification. Both groups of patients were treated with stratified chemotherapy by risk according to the CNCL-B-NHL-2017 scheme. The deadline for follow-up was December 31, 2023. All the patients were examined by chromosome fluorescence in situ hybridization (FISH), and the rearrangement of genes MYC, BCL-2 and BCL-6 was confirmed. The clinical and pathological characteristics of patients at disease onset were analyzed, and the therapeutic effects of patients in different clinical stages and risk groups were compared. Survival analysis was drawn by Kaplan Meier method, the log-rank test was used to compare the differences in the cumulative survival rate between different groups, and multivariate Cox regression model was used to identify the prognostic factors. Results: A total of 62 patients were included, with an onset age [M(Q1, Q3)] of 7 (4, 11) years, including 48 males and 14 females. There were 11 (17.7%) patients in stageⅡ, 33(53.2%)patients in stage Ⅲ and 18(29.1%)patients in stage Ⅳ. FISH testing showed that 4 cases (6.5%) were HGBL-DH and 3 (4.8%) were HGBL-TH. The remaining 55 cases (88.7%) were HGBL-NOS, with 18 cases accompanied by MYC rearrangement. There were 7 cases in the HGBL-DH/TH group and 55 cases in the HGBL-NOS group. Thirteen cases (20.9%) were treated with the B1 regimen, 3 cases (4.8%) with B2 regimen, 37 cases (59.6%) with C1 regimen, and 9 cases (14.7%) with the C2 regimen. Forty-eight cases (77.4%) received rituximab therapy at the same time. Five cases (8.0%) progressed during treatment. The follow-up time [M(Q1, Q3)] was 43.5 (36.1, 53.7) months. The complete remission rate was 91.9% (57/62). The 3 year overall survival rate was 93.5% and event-free survival (EFS) rate was 91.9%. The 3-year overall survival rate in the HGBL-NOS group was higher than that in the HGBL-DH/TH group (96.3% vs 71.4%, P=0.011). The 3-year EFS rate of the HGBL-NOS group was higher than that of the HGBL-DH/TH group (94.5% vs 71.4%, P=0.037). In the HGBL-NOS subgroup, the overall survival rate of children with MYC rearrangement was lower (100% vs 88.9%,P=0.039). Multivariate Cox regression analysis showed that central invasion (HR=6.05, 95%CI: 1.96-38.13, P=0.046) was a risk factor for overall survival. Conclusion: CNCL-B-NHL-2017 regimen shows significant effects in the treatment of pediatric HGBL, with a good prognosis.

[Long-term efficacy and prognostic factors of Beijing Children's Hospital-2009-lymphoblastic lymphoma in the treatment of T-lymphoblastic lymphoma in children and adolescents].

Objective: To summarize the long-term efficacy of Beijing Children's Hospital-2009-lymphoblastic lymphoma (BCH-2009-LBL) in the treatment of T-lymphoblastic lymphoma (T-LBL) in children and adolescents and to explore the prognostic factors. Methods: T-LBL children admitted to Beijing Children's Hospital Affiliated to Capital Medical University from January 2009 to April 2017 were retrospectively included. According to clinical stage, prognostic genes and treatment response, the children were divided into low, intermediate and high risk groups, and stratified treatment was performed according to the BCH-2009-LBL protocol, with follow-up until December 31, 2023. The clinical characteristics and therapeutic effect of each group were compared. Survival curve was drawn by Kaplan-Meier method, and the difference in survival rate between groups was compared by log-rank test. Multivariate Cox regression model was used to analyze the prognostic factors. Results: A total of 146 patients were included, the age of disease onset [M(Q1, Q3)] was 8.0 (1.5, 14.0) years old. There were 107 (73.3%) males and 39 (26.7%) females. Clinical staging: 1 case in stage Ⅰ and 1 case in stage Ⅱ (0.7% each), 41 cases (28.1%) cases in stage Ⅲ and 103 cases(70.5%) in stage Ⅳ. There were 1 case (0.7%), 93 cases (63.7%), and 52 cases (35.6%) in the low, intermediate, and high-risk groups, respectively. The follow-up time was 121 (80, 180) months, and the 5-year and 10-year event-free survival (EFS) rates were 76.4% and 75.0%, respectively. The 5-year EFS rates of low, intermediate and high risk groups were 100.0%, 81.3% and 67.3%, respectively. There was significant difference in remission between the middle-risk group and the high-risk group on the 8th day of hormone pretreatment and at the end of induction (both P<0.05). Recurrence/progression occurred in 29 cases (recurrence rate 19.9%), and the recurrence time was 15 (3, 74) months, in which 26 cases died and only 3 cases survived. Infection-related death occurred in 6 cases (4.1%). The failure or progression of hormone pretreatment at d8 (HR=10.089, 95%CI: 1.266-80.387, P=0.029) and the failure to achieve complete remission at the end of induction (mid-term evaluation) (HR=7.638, 95%CI: 2.411-24.199, P=0.001) were the risk factors for EFS rate of intermediate risk group. The above indexes had no statistical significance on EFS rate in high-risk groups (all P>0.05). Conclusions: BCH-2009-LBL regimen shows good efficacy in the treatment of pediatric T-LBL. The failure or progression of hormone pretreatment at d8 and the failure to achieve complete remission at the end of induction (mid-term evaluation) were the risk factors for EFS rate.

[Analysis of 10 cases of brentuximab vedotin combined with chemotherapy in the treatment of children with refractory and or relapsed classic Hodgkin lymphoma].

Objective: To evaluate the efficacy and safety of CD30 antibody-drug conjugates (ADC) brentuximab vedotin (BV) combined with chemotherapy in children with refractory or relapsed classic Hodgkin's lymphoma (R/R cHL). Methods: Clinical data (including age, gender, B symptoms, clinical stage, previous treatment, etc.) of the 10 R/R cHL children diagnosed and treated at Beijing Children's Hospital Affiliated to Capital Medical University from October 2021 to August 2023 were analyzed retrospectively. According to the different intensity of chemotherapy drugs, the dose of BV applied in the same course of treatment was 1.8 mg/kg for BV applied once every 3 weeks, and 1.2 mg/kg for BV applied once every 2 weeks. All 10 patients received at least 2 cycles of BV combined with chemotherapy and were evaluated every 2 cycles. The patients were followed up until May 31, 2024. The infusion reactions and adverse reactions after treatment were recorded. Results: In all 10 patients, there were 7 males and 3 females, the age ranged from 5.3-16.9 years, and there were 6 cases of refractory and 4 cases of relapsed. There were 6 cases of nodular sclerosis type, 2 cases of mixed cell type, 1 case of lymphocyte-rich type, and 1 case of lymphodepletion type. There were 5 cases of stage Ⅳ and 5 cases of stage Ⅲ. Previous treatment was mainly chemotherapy, 4 cases received radiotherapy and 1 case received programmed cell death protein 1 (PD-1) antibody therapy. The follow-up time ranged from 9 to 27 months. A total of 43 courses with 49 doses of BV alone or combined with chemotherapy were recorded, and the number of courses was 2 to 10 times. All 10 children responded to the treatment, and 9 achieved complete remission. BV infusion was successfully completed in all cases. A total of 28 cases of grade 3 or above adverse events were recorded, mainly myelosuppression, all of which were related to chemotherapy and did not affect sequential treatment. Conclusion: Brentuximab vedotin has demonstrated efficacy and a tolerable safety profile in the treatment of refractory and relapsed CD30-positive Hodgkin's lymphoma in children.

[Porphyromonas gingivalis persisters induce the immuno-inflammatory responses in macrophages by upregulating the forkhead box1 signaling pathway].

Objective: To investigate the effects of Porphyromonas gingivalis (Pg) persisters (Ps) on immuno-inflammatory responses in macrophages, and to explore the underlying mechanisms. Methods: Pg cells were cultured to the stationary phase (72 h), and subsequently treated by high concentration of metronidazole at 100 mg/L, amoxicillin at 100 mg/L and the combination of them for different time period, named as metronidazole group, amoxicillin group and (metronidazole+amoxicillin) group. Pg cells without treatment were used as Blank control. The survival profile of PgPs cells was measured by colony-forming unit assay. The living state of PgPs was observed by Live/Dead staining. Then, Pg and metronidazole-treated PgPs (M-PgPs) were used to treat macrophages, named as Pg group and M-PgPs group. Transmission electron microscopy (TEM) was used to observe the bacteria in the macrophages. The expression levels of proinflammatory cytokines in macrophages were determined by real-time fluorescence quantitative PCR and enzyme-linked immunosorbent assay. The location of forkhead box transcription factor 1 (FOXO1) was detected by confocal immunofluorescence microscopy. After inhibiting or enhancing the FOXO1 expressions using inhibitors (Fi) or activators (Fa) respectively, the macrophages were treated with Pg and M-PgPs, divided as Blank group, Pg group, M-PgPs group, Fi group, (Fi+Pg) group, (Fi+M-PgPs) group, Fa group, (Fa+Pg) group and (Fa+M-PgPs) group. Then, the expression pattens of proinflammatory cytokines were assessed. Results: Remarkable number of lived PgPs was observed, both in planktonic culture and Pg biofilms either treated with metronidazole, amoxicillin or both, and those persisters could form new colonies. Pg and M-PgPs were able to enter into the macrophages and the protein expression levels of interleukin (IL)-1ß, IL-6, IL-8 and tumor necrosis factor-α (TNF-α) [Pg group: (2 392±188), (162±29), (5 558±661), (789±155) µg/L; M-PgPs group: (2 415±420), (155±3), (5 732±782), (821±176) µg/L] were significantly upregulated than those in Blank group [(485±140), (21±9), (2 332±87), (77±7) µg/L] (P<0.01). Moreover, Pg and M-PgPs could facilitate the nuclear translocation and accumulation of FOXO1. In addition, the relative mRNA expression levels of FOXO1, B-cell lymphoma 6 and Krüppel-like factor 2 were upregulated when compared to Blank group (P<0.05). Furthermore, the protein expression levels of IL-1ß, IL-6, IL-8 and TNF-α in Fi+Pg group [(1 081±168), (70±8), (1 976±544), (420±47) µg/L] were remarkably lower than Pg group [(4 411±137), (179±6), (5 161±929), (934±24) µg/L] (P<0.05). Similarly, the protein expression levels of IL-1ß, IL-6, IL-8 and TNF-α in Fi+M-PgPs group [(1 032±237), (74±10), (1 861±614), (405±32) µg/L] were remarkably lower than M-PgPs group [(4 342±314), (164±17), (4 438±1 374), (957±25) µg/L] (P<0.05). On the contrary, the protein expression levels of IL-1ß, IL-6, IL-8 and TNF-α in Fa+Pg group [(8 198±1 825), (431±28), (8 919±650), (2 186±301) µg/L] and Fa+M-PgPs group [(8 159±2 627), (475±26), (8 995±653), (2 255±387) µg/L] were significantly higher than Pg group and M-PgPs group, respectively (P<0.05). Conclusions: PgPs are highly tolerant to metronidazole and amoxicillin. The M-PgPs could enhance the immuno-inflammatory responses in macrophages by upregulating the FOXO1 signaling pathway, while this effect exhibits no significant difference with Pg.

[Clinical analysis of adverse reactions in patients with multidrug-resistant and rifampicin-resistant pulmonary tuberculosis treated with delamanid-containing regimen].

Objective: To explore the characteristics of adverse drug reactions during the 24-week therapy with delamanid-containing regimen for patients with multidrug-resistant and rifampicin-resistant pulmonary tuberculosis (MDR/RR-PTB). Methods: The prospective multicenter study was conducted from June 2020 to June 2023. A total of 608 eligible patients with MDR/RR-PTB were enrolled in 26 tuberculosis medical institutions in China including 364 males and 79 females, aged 39.6(19.0-68.0) years. Patients were treated with chemotherapy regimens containing delamanid. Patients were closely supervised during treatment of medication, and all adverse reactions occurring during treatment were monitored and recorded. The clinical characteristics of adverse reactions were evaluated by descriptive analysis. Chi-square test and multivariate logistic regression were used to analyze the related factors of QTcF interval prolongation (QT corrected with Fridericia's formula). Results: Of the 608 patients enrolled in this study, 325 patients (53.5%) reported 710 adverse events within 24 weeks of treatment. The top 6 most common complications were hematological abnormalities (143 patients, 23.5%), QT prolongation (114 patients, 18.8%), liver toxicity (85 patients, 14.0%), gastrointestinal reaction (41 patients, 6.7%), peripheral neuropathy (25 patients, 4.1%) and mental disorders (21 patients, 3.5%). The prolongation of QT interval mostly occurred in the 12th week after the first dose of medication. Serious adverse reactions occurred in 21 patients (3.5%). There were 7 patients (1.2%) with mental disorders, including 2 patients (0.3%) with severe mental disorders. Conclusions: The safety of dalamanid-based regimen in the staged treatment of MDR/RR-PTB patients was generally good, and the incidence of adverse reactions was similar to that reported in foreign studies. This study found that the incidence of QT interval prolongation in Chinese patients was higher than that reported overseas, suggesting that the monitoring of electrocardiogram should be strengthened when using drugs containing delamanid that may cause QT interval prolongation.

[Bioinformatic analysis of CCND2 expression in papillary thyroid carcinoma and its impact on immune infiltration].

OBJECTIVE: To investigate cyclin D2 (CCND2) expression in papillary thyroid carcinoma (PTC) and its association with the clinicopathological features. METHODS: The public databases TCGA, TIMER 2.0 and UALCAN were used to explore CCND2 expression level in PTC and adjacent tissues, and its diagnostic value for PTC was analyzed using ROC curves. GO enrichment analysis of CCND2-related differentially expressed genes (DEGs) in PTC was performed, and tumor immune infiltration of CCND2 in thyroid cancer was analyzed using TIMER database and CIBERSORT data source. RT-qPCR and Western blot were used to detect CCND2 expression in normal human thyroid cell line Nthy-ori-3-1 and human PTC cell lines TPC-1 and BCPAP. CCND2 expression was also detected in clinical specimens of PTC and adjacent tissues by immunohistochemistry, and its correlation with clinicopathological features of the patients were analyzed. RESULTS: Informatic analysis revealed significantly higher CCND2 mRNA expression in thyroid cancer than in the adjacent tissues (P < 0.001) in close correlation with tumor stage, gender, age, pathological subtype, and lymph node involvement (P < 0.05). ROC curve analysis showed that at the cutoff value of 4.983, the diagnostic sensitivity, specificity, and accuracy of CCND2 expression for PTC was 83.6%, 94.9%, and 78.5%, respectively. CCND2 expression was positively correlated with B cells, CD4+ T cells, and macrophages (P < 0.001) and negatively with CD8+ T cells (P < 0.01), and also correlated with memory B-cell infiltration, CD4+ T-cell memory activation, M2 macrophages, resting mast cells, and mast cell activation (P < 0.05). RT-qPCR, Western blot and immunohistochemistry showed significantly higher CCND2 expression in the PTC cells than in Nthy-ori-3-1 cells (P < 0.01) and also in clinical PTC tissues than in the adjacent tissues (P < 0.05) in correlation with tumor size, lymph node metastasis and TNM stage (P < 0.05). CONCLUSION: CCND2 overexpression is closely correlated with tumor progression and immune cell infiltration in PTC patients..

[Application of seamless phase â ¡/â ¢ design in vaccine clinical trials].

The seamless phase Ⅱ/Ⅲ design integrates independent phase Ⅱ and phase Ⅲ clinical trials into a continuous, phased adaptive clinical trial design. Compared with traditional independent phase Ⅱ and phase Ⅲ clinical trials, the seamless design offers significant advantages in accelerating drug or vaccine development and improving clinical trial efficiency. Currently, the application of this design in anti-tumor drug research is becoming increasingly mature, and it is gradually expanding to clinical trials of vaccines, including the 9-valent human papillomavirus vaccine, sabin strain inactivated polio vaccine, and others. This paper aims to clarify the seamless phase Ⅱ/Ⅲ design concept and offer valuable insights into its implementation. It accomplishes this by presenting a clinical trial example featuring a phase Ⅱ/Ⅲ seamless design for a 9-valent human papillomavirus vaccine. The article delves into the specific considerations and potential challenges related to implementing the seamless design, aiming to provide valuable insights for optimizing vaccine clinical trials within our country.

[Clinical study of 15 cases of primary non-immunodeficient central nervous system lymphoma in children].

Clinical data of 15 primary central nervous system lymphoma (PCNSL) children aged ≤18 years admitted to our hospital between May 2013 to May 2023 were retrospectively analyzed. Our goal was to summarize the clinical features of children and investigate the therapeutic effect of a high-dose methotrexate (HD-MTX) based chemotherapy regimen on this disease. The male-to-female ratio was 2.7∶1, and the median age was 7.2 (2.3-16.4) years at diagnosis. The initial clinical symptoms were primarily cranial hypertension, with imaging findings revealing multiple lesions. Pediatric PCNSL with normal immune function has a favorable prognosis with HD-MTX-based chemotherapy. Patients with a stable disease can be treated with minimal or no maintenance. HD-MTX-based chemotherapy remains effective when the disease progresses or recurs after an initial course of non-HD-MTX-based chemotherapy.

[Exploration of the method and efficacy of treatments for intractable pelvic pain caused by rectal or bladder fistula].

Objective: To explore the causes and therapeutic effects of pelvic pain caused by rectal fistula or bladder fistula after comprehensive treatment of cervical cancer and rectal cancer (radiotherapy, surgery, chemotherapy, and other treatments). Methods: A retrospective analysis was conducted on the clinical and pathological data of patients with pelvic tumors admitted to the First People's Hospital of Yinchuan City, Ningxia and the Affiliated Cancer Hospital of Zhengzhou University from June 2016 to June 2022. The causes of persistent pelvic pain in patients after comprehensive treatment was investigated, and the corresponding therapeutic effects after clinical treatment was observed. Results: Thirty-two tumor patients experienced persistent pain after comprehensive treatment, including 22 cases of cervical cancer and 10 cases of rectal cancer. The preoperative pain of the entire group of patients was evaluated using the digital grading method, with a pain score of (7.88±1.31) points. Among the 32 patients, there were 16 cases of rectovaginal fistula or ileovaginal fistula, 9 cases of vesicovaginal fistula, 5 cases of rectoperineal fistula, and 2 cases of vesicovaginorectal fistula. Thirty-two patients were initially treated with medication to relieve pain, and according to the ruptured organs, a fistula was made to the corresponding proximal intestinal canal and renal pelvis to intercept the intestinal contents and urine. However, the pain did not significantly be improved. The pain score of treatment with the above methods for one week was (8.13±1.13) points, and there was no statistically significant difference compared to preoperative treatment (P=0.417). In the later stage, based on a comprehensive evaluation of whether the tumor had recurred, the value of organ preservation, the benefits of surgery, the balance between survival time and improving quality of life, pathological organ resection or repair was performed. The surgical methods included repair of leaks, local debridement combined with irrigation of proximal intestinal fluid, distal closure of the sigmoid colon combined with proximal ostomy, posterior pelvic organ resection, anterior pelvic organ resection, and total pelvic organ resection. One week after surgery, the patients' pain completely relieved or disappeared, with the pain score of (1.72±1.37) points, which was significantly divergent from the preoperative and initial surgical treatments (P＜0.001). Conclusions: Palliative pyelostomy and proximal enterostomy cannot effectively alleviate persistent pelvic floor pain. The fundamental way to alleviate pain is complete blocking of the inflammatory erosion of the intestinal fluid and urine.

Edge State, Band Topology, and Time Boundary Effect in the Fine-Grained Categorization of Chern Insulators.

We predict novel topological phases with broken time-reversal symmetry supporting the coexistence of opposite chiral edge states, which are fundamentally different from the photonic spin-Hall, valley-Hall, and higher-order topological phases. We find a fine-grained categorization of Chern insulators, their band topologies characterized by identical Chern numbers are completely different. Furthermore, we prove that different topologies cause zeros in their Bloch wave function overlaps, which imprint the band gap closing and appear at the degenerate points of topological phase transition. The Bloch wave function overlaps predict the reflection and refraction at a topological time boundary, and the overlap zeros ensure the existence of vanishing revival amplitude at critical times even though different topologies before and after the time boundary have identical Chern numbers. Our findings create new opportunities for topological metamaterials, uncover the topological feature hidden in the time boundary effect as a probe of topology, and open a venue for the exploration of the rich physics originating from the long-range couplings.

Comparison of different dosages of propofol combined with its equivalent alfentanil in outpatient abortion: a prospective, double-blinded, randomized trial.

OBJECTIVE: This study aimed at determining the optimal dose combination of alfentanil and propofol for outpatient abortion anesthesia. PATIENTS AND METHODS: The study was separated into two parts. In the first part, patients were to determine the median effective dose (ED50) and the 95% effective dose (ED95) of alfentanil in combination with 2.5 mg·kg-1 propofol to inhibit body movements during the abortion using the Dixon up-and-down sequential allocation method. In the second part, 170 patients were randomly divided into group C (2.0 mg·kg-1 propofol with alfentanil 12.16 µg·kg-1) and group E (2.5 mg·kg-1 propofol with its ED95) to compare the anesthetic effect. The primary outcome was the sedation level during general anesthesia. The secondary outcomes were circulation, respiratory complications, and postoperative recovery quality. RESULTS: The ED50 and the ED95 values of alfentanil were 3.37 µg·kg-1 (95% CI: 2.58-3.97 µg·kg-1) and 4.68 µg·kg-1 (95% CI: 4.04-9.32 µg·kg-1). The frequency of deep sedation in group E was significantly higher than in group C (76.5% vs. 60%). Patients in group C showed more wakefulness even during the surgery (14.3% vs. 4.4%). The results of our exploratory analyses did not reveal differences in respiratory depression, circulatory depression, postoperative side effects, or recovery outcomes. CONCLUSIONS: The combination of 2.5 mg·kg-1 propofol and 4.68 µg·kg-1 alfentanil produces a better sedative effect than the combination of 2.0 mg·kg-1 propofol and 12.16 µg·kg-1 alfentanil without increasing additional risks associated with anesthesia.

The safety and feasibility of same-day discharge for the management of patients undergoing pulmonary lobectomy.

OBJECTIVES: Is same-day discharge mode safe and feasible for thoracoscopic lobectomy? This study assesses the safety and feasibility of same-day discharge for patients undergoing thoracoscopic lobectomy. METHODS: We conducted a prospective cohort study from January to December 2022, all patients undergoing thoracoscopic lobectomy were screened for eligibility, and participating eligible patients were separated into a same-day discharge lobectomy (SDDL) group and an inpatient lobectomy (InpL) group based upon length of stay. All discharged patients underwent 30-day postoperative follow-up performed by a team of medical professionals. In addition, eligible patients that underwent thoracoscopic lobectomy from January to December 2021 were included in the historical lobectomy (HisL) group. RESULTS: Of the 52 patients that met the eligibility criteria for same-day discharge, 17 were discharged within 24 h after surgery. In the SDDL group, of whom 1 (5.9%) underwent emergency treatment and readmission within 30 days after surgery due to a pulmonary infection, no patients experienced complications such as reoperation, air leakage, atelectasis, chylothorax, or blood transfusion events during the follow-up period. No differences in overall postoperative complication rates were detected between the SDDL and InpL groups (P>0.05), there was a non-significantly higher rate of readmission and emergency visits in the SDDL group relative to the other two groups (P>0.05). CONCLUSIONS: These results emphasize the safety and feasibility of same-day discharge for patients undergoing thoracoscopic lobectomy, it may further revolutionize the general approach to the hospitalization of thoracoscopic lobectomy patients.

Relativistic ultrafast electron diffraction at high repetition rates.

The ability to resolve the dynamics of matter on its native temporal and spatial scales constitutes a key challenge and convergent theme across chemistry, biology, and materials science. The last couple of decades have witnessed ultrafast electron diffraction (UED) emerge as one of the forefront techniques with the sensitivity to resolve atomic motions. Increasingly sophisticated UED instruments are being developed that are aimed at increasing the beam brightness in order to observe structural signatures, but so far they have been limited to low average current beams. Here, we present the technical design and capabilities of the HiRES (High Repetition-rate Electron Scattering) instrument, which blends relativistic electrons and high repetition rates to achieve orders of magnitude improvement in average beam current compared to the existing state-of-the-art instruments. The setup utilizes a novel electron source to deliver femtosecond duration electron pulses at up to MHz repetition rates for UED experiments. Instrument response function of sub-500 fs is demonstrated with < 100 fs time resolution targeted in future. We provide example cases of diffraction measurements on solid-state and gas-phase samples, including both micro- and nanodiffraction (featuring 100 nm beam size) modes, which showcase the potential of the instrument for novel UED experiments.

[Development of dental robot implantation technology].

With the advancement of technology, intelligent technology has achieved unprecedented progress and breakthroughs in various fields. Dental implant robots represent a significant leap in the field of dental medical technology. This article aims to review the development of dental robot implantation technology both domestically and internationally, to compare the similarities and differences between existing dental implant methods and robotic implantation, to analyze the characteristics and current applications of robotic implantation technology, and to provide a forward-looking perspective. This review summarized 63 literatures and compared 1 176 implants, dental robot implantation demonstrates significant advantages in terms of precision, efficiency, and minimally invasive procedures. It effectively addresses issues such as implant position deviation, limited surgical visibility, and restricted operating space associated with traditional implantation methods. With widespread adoption in the future, it may reduce the overall technological expenses, and optimize its advantages and potential benefits.

Screening of m6A gene-related lncRNAs in colon adenocarcinoma and construction of a prognostic prediction model.

OBJECTIVE: We aimed to screen the long non-coding RNAs (lncRNAs) related to N6-methyladenosine (m6A) gene and build the prognostic prediction model of colon adenocarcinoma (COAD). MATERIALS AND METHODS: The RNA sequencing data of 435 COAD cases with clinical survival and prognosis information and the GSE39582 dataset were obtained from TCGA and GEO, respectively. The lncRNAs related to the m6A gene with significant independent prognosis were identified. We used Cox regression analyses to acquire the lncRNAs associated with prognosis. Moreover, we built a prognostic prediction model of COAD. The Cox regression analyses were applied to obtain the independent prognostic clinical factors. Furthermore, we built the ceRNA regulation network of COAD, and the gene ontology (GO) and Kyoto Encyclopedia of Genes (KEGG) enrichment analysis for the lncRNAs was applied. RESULTS: Overall, 5 lncRNAs (MAGI1-IT1, CSNK1G2-AS1, ALMS1-IT1, LINC01341, LOXL1-AS1) related to m6A gene with significant independent prognosis were acquired. A prognostic prediction model of COAD was built, and 4 correlation-independent prognostic factors were found. In addition, the ceRNA regulation network of COAD was built, and mRNAs were significantly enriched in the 15 GO biological processes (such as regulation of transcription) and in 14 KEGG pathways (such as taurine). CONCLUSIONS: We identified 5 lncRNAs related to the m6A gene with significant independent prognosis. The ceRNA regulation network of COAD was built, which has great significance for identifying the biomarkers associated with m6A in COAD.