[The safety and efficacy of blinatumomab in the treatment of B-cell acute lymphoblastic leukemia in children].

To explore the safety and efficacy of blinatumomab in the treatment of CD19 positive (CD19+) B-cell acute lymphoblastic leukemia (B-ALL) in children. A retrospective analysis was conducted on the clinical data of pediatric B-ALL patients who received blinatumomab treatment from Hematology & Blood Diseases Hospital of Chinese Academy of Medical Sciences from August 2021 to October 2023. Based on their disease status, the patients were divided into refractory/relapsed(RR) group, minimal residual disease clearance (MC) group, and chemotherapy intolerance (IC) group. Clinical data of the children were collected to evaluate the adverse drug reactions, therapeutic efficacy and survival of the children. In total, 35 patients were included, with 20 males and 15 females, aged from 0.6 to 16.4 (9.9±4.2) years old. There were 10 cases in the RR group, 20 cases in the MC group and 5 cases in the IC group. A total of 56 cycles of infusion were completed, with one cycle in 24 cases, two cycles in 5 cases, three cycles in 2 cases and four cycles in 4 cases. The median infusion time [M (Q1, Q3)] from the first to the fourth cycle was 14 (14, 28) days, 28 (28, 28) days, 28 (28, 28) days and 28 (26, 28) days, respectively. In terms of adverse reactions, the incidence of grade 1-2 cytokine release syndrome(CRS) was 57.1% (32/56), with grade 1 CRS accounting for 84.4% (27/32). The incidence rate of immune effector cell-associated neurotoxicity syndrome(ICANS) (grade 4) was 1.8% (1/56). In the RR group, 6 cases were treated effectively, and minimal residual disease(MRD) turned negative, before treatment, MRD levels were all less than 20%. Among them, 3 cases had MRD turning positive again 14 to 42 days after discontinuation of Belintoumab. Four cases were treated ineffectively, with MRD >20% before treatment. All MRD positive cases in MC group turned negative and all MRD negative cases in the IC group remained negative after treatment. The median follow-up time of RR group was 5.7 (3.8, 9.4) months, and 1 year median survival rate and event-free survival rate were 40.0%±21.9% and 33.3%±19.2%, respectively. The median follow-up time for MC and IC group patients was 6.7 (5.2, 12.5) months and 7.1 (5.1, 7.6) months, respectively, with an event free survival rate of 100%. The safety and efficacy of using belintoumab in partial RR, MRD clearance, and chemotherapy intolerance are good.

[Clinical features and prognostic factors of advanced myelodysplastic syndromes in children].

Objective: To investigate the clinical features and prognostic factors of advanced myelodysplastic syndromes (MDS) in children. Methods: Clinical data of children diagnosed with advanced MDS in the Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences, between September 2009 and April 2022 were retrospectively collected. Follow-up assessments were performed through telephone interviews and the review of medical records until May 1, 2023. The clinical features of children with advanced MDS were summarized by analyzing chromosomal karyotype tests, second-generation gene sequencing results. Multivariate Cox regression analysis was used to investigate the prognostic factors of advanced MDS in children. Results: A total of 69 children, comprising 49 males and 20 females, aged [M (Q1, Q3)] 8 (5, 10) years, were enrolled in the study. Sixty-seven cases underwent chromosomal karyotype testing, of which 42 cases (62.7%) had abnormal karyotypes, with monosomy 7 the most common in 17 cases (25.4%). Forty-three cases underwent next-generation sequencing, with mutations in the SETBP1, NRAS, PTPN11 and RUNX1 genes more common, identified in 12 cases (27.9%), 9 cases (20.9%), 8 cases(18.6%), and 8 cases(18.6%), respectively. The follow-up time [M (Q1, Q3)] was 26 (13, 56) months and the 5-year overall survival rate was 56%(95%CI: 44.4%-70.5%). The 5-year overall survival rate for children who underwent hematopoietic stem cell transplantation (HSCT) was higher than that of children who did not undergo HSCT (73.9% vs 29.1%, P<0.001). HSCT (HR=0.118, 95%CI: 0.037-0.372, P<0.001) was a protective factor for the overall survival rate of children with advanced MDS. Serum ferritin level>356.3 µg/L (HR=6.497, 95%CI: 2.068-20.415, P=0.001) and moderate to severe splenomegaly (HR=4.075, 95%CI: 1.174-14.141, P=0.027) were risk factors for the overall survival rate of children with advanced MDS. Conclusions: Monosomy 7 was the most common abnormal karyotype and SETBP1 was the gene that had the highest mutation frequency in children with advanced MDS. HSCT, increased ferritin and moderate to severe splenomegaly are prognostic factors influencing the overall survival rate of children with advanced MDS.

PLATELET-RICH PLASMA VERSUS CORTICOSTEROID IN THE TREATMENT OF KNEE OSTEOARTHRITIS: A SYSTEMATIC REVIEW AND META-ANALYSIS OF RANDOMIZED CONTROLLED TRIALS.

The aim of this meta-analysis is to evaluate the clinical effectiveness of intra-articular injections of platelet-rich plasma (PRP) versus corticosteroid (CS) in treating knee osteoarthritis (KOA). A comprehensive search of the PubMed, Embase, and Web of Science databases was conducted for literature on intra-articular PRP and CS injections for the treatment of knee osteoarthritis, with the search period extending to December 2023. The risk of bias was assessed using the Cochrane Risk of Bias tool, and statistical analysis was subsequently carried out using Review Manager 5.4.1 software. The efficacy of PRP versus CS injections across various studies was compared based on the weighted mean difference and 95% confidence interval for scores from the Visual Analogue Scale (VAS), Knee Osteoarthritis Outcome Score (KOOS), and the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). In our analysis, we incorporated twelve studies encompassing a total of 801 joints, of which 404 were in the PRP group and 397 in the CS group. PRP group was significantly reduced the VAS score than CS group in 3-month (P=0.003), 6-month (P=0.007) and 9-month (P<0.00001); PRP group was significantly reduced the WOMAC total score compared to CS group in 1-month (P=0.01), 6-month (P=0.003), 9-month (P=0.005) and 12-month (P<0.00001); In 3-month and 6-month, PRP group were significantly increased the KOOS pain relief score (3-month: P=0.002, 6-month: P<0.00001), the KOOS activities of daily living scores (3-month: P<0.00001, 6-month: P<0.00001) and the KOOS quality of life score (3-month: P=0.003, 6-month: P<0.00001) compared to CS group; PRP group also were significantly increased the KOOS sports score in 3-month compared to CS group (P=0.04). The leukocyte-poor PRP (LP-PRP) group was significantly reduced the VAS score compared to CS group (P=0.04). Recent findings indicate that intra-articular injections of PRP yield superior results in alleviating pain and enhancing functionality in individuals with knee osteoarthritis, as opposed to CS injections. During short-term follow-up, no significant difference was observed between knee injections of PRP and CS. However, the benefits of PRP injections primarily become apparent in the medium to long-term management of clinical symptoms, including pain relief, enhancing patients' quality of life, increasing activities of daily living, and improving sports capabilities.

[Analysis of the efficacy and safety of bone disease treatment in patients with newly diagnosed multiple myeloma treated with denosumab or zoledronic acid].

Objective: This study investigated the efficacy and safety of denosumab (DENOS) versus zoledronic acid (ZOL) in the bone disease treatment of newly diagnosed multiple myeloma. Methods: The clinical data of 80 patients with myeloma bone disease (MBD) at the Fifth Medical Center of PLA General Hospital between March 1, 2021 and June 30, 2023 were retrospectively reviewed. Eighteen patients with severe renal impairment (SRI, endogenous creatinine clearance rate<30 ml/min) were treated with DENOS, and 62 non-SRI patients were divided into DENOS (30 patients) and ZOL group (32 patients) . Results: Hypocalcemia was observed in 26 (33%) patients, and 22 patients developed hypocalcemia during the first treatment course. The incidence of hypocalcemia in the non-SRI patients of DENOS group was higher than that in the ZOL group [20% (6/30) vs 13% (4/32), P=0.028]. The incidence of hypocalcemia in SRI was 89% (16/18). Multivariate logistic regression analysis revealed that endogenous creatinine clearance rate<30 ml/min was significantly associated with hypocalcemia after DENOS administration (P<0.001). After 1 month of antiresorptive (AR) drug application, the decrease in the serum ß-C-terminal cross-linked carboxy-telopeptide of collagen type I concentrations of SRI and non-SRI patients in the DENOS group were significantly higher than that in the ZOL group (68% vs 59% vs 27%, P<0.001). The increase in serum procollagen type Ⅰ N-terminal propeptide concentrations of patients with or without SRI in the DENOS group were significantly higher than that in the ZOL group (34% vs 20% vs 11%, P<0.05). The level of intact parathyroid hormone in each group increased after AR drug treatment. None of the patients developed osteonecrosis of the jaw and renal adverse events, and no statistically significant differences in the overall response rate, complete remission and stringent complete remission rates were found among the groups (P>0.05), and the median PFS and OS time were not reached (P>0.05) . Conclusions: In the treatment of MBD, DENOS minimizes nephrotoxicity and has strong AR effect. Hypocalcemia is a common adverse event but is usually mild or moderate and manageable.

[Analysis of therapeutic effects of allogeneic hematopoietic stem cell transplantation in 12 patients with DEK-NUP214 fusion gene positive acute myeloid leukemia].

Twelve DEK-NUP214 fusion gene-positive patients with acute myeloid leukemia and on allo-HSCT treatment at the Hematology Hospital of the Chinese Academy of Medical Sciences from November 2016 to August 2022 were included in the study, and their clinical data were retrospectively analyzed. The patients comprised five men and seven women with a median age of 34 (16-52) years. At the time of diagnosis, all the patients were positive for the DEK-NUP214 fusion gene. Chromosome karyotyping analysis showed t (6;9) (p23;q34) translocation in 10 patients (two patients did not undergo chromosome karyotyping analysis), FLT3-ITD mutation was detected in 11 patients, and high expression of WT1 was observed in 11 patients. Nine patients had their primary disease in the first complete remission state before transplantation, one patient had no disease remission, and two patients were in a recurrent state. All patients received myeloablative pretreatment, five patients received sibling allogeneic hematopoietic stem cell transplantation, and seven patients received haploid hematopoietic stem cell transplantation. The median number of mononuclear cells in the transplant was 10.87 (7.09-17.89) ×10(8)/kg, and the number of CD34(+) cells was 3.29 (2.53-6.10) ×10(6)/kg. All patients achieved blood reconstruction, with a median time of 14 (10-20) days for neutrophil implantation and 15 (9-27) days for platelet implantation. The 1 year transplant-related mortality rate after transplantation was 21.2%. The cumulative recurrence rates 1 and 3 years after transplantation were 25.0% and 50.0%, respectively. The leukemia free survival rates were (65.6±14.0) % and (65.6±14.0) %, respectively. The overall survival rates were (72.2±13.8) % and (72.2±13.8) %, respectively.

[Clinical, imaging, and pathological characteristics of 35 cases of mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes syndrome].

Objective: To summarize the clinical, imaging, and pathological characteristics of mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes syndrome (MELAS) to improve the diagnosis of this rare disease. Methods: A retrospective case series was conducted to collect the clinical data and results of genetic testing, muscle biopsy, and imaging studies including computed tomography (CT), magnetic resonance imaging (MRI), and magnetic resonance spectroscopy (MRS) of 35 patients with MELAS admitted to the Nanjing Drum Tower Hospital from 2012 to 2021. Descriptive statistical analysis including mean, standard deviation, and frequency percentage were carried out. Results: The average age of onset of the patients was 30.2±2.3 years; the prevalence of family history was 20%. The two main initial symptoms were limb weakness and convulsions. The clinical manifestations of the neuromuscular system were proximal muscle weakness and exercise intolerance. The endocrine system is the most affected outside the neuromuscular system, with diabetes being the most common condition. Among the five patients who underwent brain CT, four showed hypodense lesions and two had calcified lesions. Brain MRI in 26 patients showed that the lesions more often affected the parietal lobe, basal ganglia, temporal lobe, occipital lobe, and frontal lobe than the infratentorial areas. Twelve of these individuals exhibited different levels of brain atrophy. Among the 10 patients who underwent 1H-MRS, nine showed a decrease in N-acetylaspartate (NAA) levels, eight exhibited abnormal lactate elevation (Lac peaks), whereas six had both reduced NAA levels and the presence of Lac peaks. Thirty-one patients underwent genetic testing; among them, 25 were found to have the mt.3243A>G mutation, while the remaining six exhibited rare gene alterations. Muscle biopsies were performed in 21 patients, and 15 showed abnormal mitochondrial proliferation manifested by ragged red fibers and defective oxidative phosphorylation manifested by cytochrome C oxidase (COX) enzyme-deficient muscle fibers. Conclusion: The clinical manifestations of MELAS syndrome are variable and complex, and early atypical symptoms could be missed or misdiagnosed. A detailed clinical history, imaging MRS analysis, muscle biopsy, and genetic testing are necessary to confirm the accurate diagnosis of MELAS.

[Analysis of the efficacy and prognostic factors of allogeneic hematopoietic stem cell transplantation in patients with myelodysplastic syndrome with blastomycosis and survival comparison of different subtypes after the WHO 2022 reclassification].

Objective: To evaluate the efficacy and prognostic factors of allogeneic hematopoietic stem cell transplantation (allo-HSCT) in patients with myelodysplastic syndrome accompanied by myelodysplasia (MDS-EB) and to compare the prognosis of different subtypes of patients classified by World Health Organization (WHO) 2022. Methods: A total of 282 patients with MDS-EB who underwent allo-HSCT at the Hematology Hospital of the Chinese Academy of Medical Sciences from October 2006 to December 2022 were included in the study. The WHO 2022 diagnostic criteria reclassified MDS into three groups: myelodysplastic tumors with type 1/2 of primitive cell proliferation (MDS-IB1/IB2, 222 cases), MDS with fibrosis (MDS-f, 41 cases), and MDS with biallelic TP53 mutation (MDS-biTP53, 19 cases). Their clinical data were retrospectively analyzed. Results: ① The median age of 282 patients was 46 (15-66) years, with 191 males and 91 females. Among them, 118 (42% ) and 164 (58% ) had MDS-EB1 and MDS-EB2, respectively. ②Among the 282 patients, 256 (90.8% ) achieved hematopoietic reconstruction after transplantation, with 11 (3.9% ) and 15 (5.3% ) having primary and secondary implantation dysfunctions, respectively. The cumulative incidence of acute graft-versus-host disease (GVHD) 100 days post-transplantation was (42.6±3.0) %, and the cumulative incidence of grade Ⅱ-Ⅳ acute GVHD was (33.0±2.8) %. The cumulative incidence of chronic GVHD 1 year post-transplantation was (31.0±2.9) %. Post-transplantation, 128 (45.4% ), 63 (22.3% ), 35 (12.4% ), and 17 patients (6.0% ) developed cytomegalovirus infection, bacteremia, pulmonary fungal infection, and Epstein-Barr virus infection. ③The median follow-up time post-transplantation was 22.1 (19.2-24.7) months, and the 3-year overall survival (OS) and disease-free survival (DFS) rates were 71.9% (95% CI 65.7% -78.6% ) and 63.6% (95% CI 57.2% -70.7% ), respectively. The 3-year non-recurrent mortality rate (NRM) is 17.9% (95% CI 13.9% -22.9% ), and the 3-year cumulative recurrence rate (CIR) is 9.8% (95% CI 6.7% -13.7% ). The independent risk factors affecting OS post-transplantation include monocyte karyotype (P=0.004, HR=3.26, 95% CI 1.46-7.29), hematopoietic stem cell transplantation complication index (HCI-CI) of ≥3 points (P<0.001, HR=2.86, 95% CI 1.72-4.75), and the occurrence of acute gastrointestinal GVHD of grade Ⅱ-Ⅳ (P<0.001, HR=5.94, 95% CI 3.50-10.10). ④The 3-year OS and DFS rates in the MDS-IB1/IB2 group post-transplantation were better than those in the MDS-biTP53 group [OS: 72.0% (95% CI 63.4% -80.7% ) vs 46.4% (95% CI 26.9% -80.1% ), P=0.020; DFS: 67.4% (95% CI 60.3% -75.3% ) vs 39.7% (95% CI 22.3% -70.8% ), P=0.015]. The 3-year CIR was lower than that of the MDS-biTP53 group [7.3% (95% CI 4.3% -11.4% ) vs 26.9% (95% CI 9.2% -48.5% ), P=0.004]. The NRM at 3 years post-transplantation in the MDS-IB1/IB2, MDS-f, and MDS-biTP53 groups were 16.7% (95% CI 12.1% -22.1% ), 20.5% (95% CI 9.4% -34.6% ), and 26.3% (95% CI 9.1% -47.5% ), respectively (P=0.690) . Conclusion: Allo-HSCT is an effective treatment for MDS-EB, with monomeric karyotype, HCI-CI, and grade Ⅱ-Ⅳ acute gastrointestinal GVHD as independent risk factors affecting the patient's OS. The WHO 2022 classification helps distinguish the efficacy of allo-HSCT in different subgroups of patients. Allo-HSCT can improve the poor prognosis of patients with MDS-f, but those with MDS-biTP53 have a higher risk of recurrence post-transplantation.

[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.

[Analysis of risk factors and construction of nomogram model for local lymph node metastasis in salivary gland mucoepidermoid carcinoma].

Objective: To analyze the risk factors affecting regional lymph node metastasis in salivary gland mucoepidermoid carcinoma (MEC) and to establish a nomogram model for individually predicting lymph node metastasis in salivary gland MEC. Methods: The clinical data of 2 152 patients with salivary gland MEC from 1975 to 2020 were collected from the Surveillance, Epidemiology, and End Results (SEER) database of the National Cancer Institute. The collected data were divided into training cohort (1 506 cases) and validation cohort (646 cases) according to the ratio of 7∶3. Single-factor regression and multi-factor logistic regression were used to screen factors related to local lymph node metastasis in salivary gland MEC, with constructing of a nomogram. Calibration curve, receiver operating characteristic (ROC) curve, area under the ROC curve (AUC) and decision curve analysis were used to evaluate model performance in the validation cohort and the total cohort. Statistical tests were performed using SPSS (26.0) and R (4.3.0) software. Results: Multivariate logistic regression results showed that M stage [OR(95%CI):12.360(3.295-46.365), P=0.014], pathological grade Ⅱ、Ⅲ、Ⅳ[OR(95%CI): 1.956(1.329-2.879), 9.654(6.309-14.772), 9.298(6.072-14.238), P<0.001], T staging T2, T3, T4[OR(95%CI): 1.706(0.932-3.124), 3.021(1.790-5.096), 3.311(1.925-5.695), P<0.001], and gender [OR(95%CI):0.759(0.593-0.972), P=0.029] were independent factors affecting local lymph node metastasis in salivary gland MEC. Through verification in the validation cohort and the total cohort, the AUC values were greater than 0.8, and the calibration curve was close to the perfect reference line, proving that the constructed nomogram model had good specificity and sensitivity for predicting local lymph node metastasis in salivary gland MEC. Conclusion: M stage, pathological grade, T stage, and gender are risk factors for predicting regional lymph node metastasis and the established-nomogram has good predictive performance for local lymph node metastasis in salivary gland MEC.

Photosymbiosis reduces the environmental stress response under a heat challenge in a facultatively symbiotic coral.

The symbiosis between corals and dinoflagellates of the family Symbiodiniaceae is sensitive to environmental stress. The oxidative bleaching hypothesis posits that extreme temperatures lead to accumulation of photobiont-derived reactive oxygen species ROS, which exacerbates the coral environmental stress response (ESR). To understand how photosymbiosis modulates coral ESRs, these responses must be explored in hosts in and out of symbiosis. We leveraged the facultatively symbiotic coral Astrangia poculata, which offers an opportunity to uncouple the ESR across its two symbiotic phenotypes (brown, white). Colonies of both symbiotic phenotypes were exposed to three temperature treatments for 15 days: (i) control (static 18 °C), (ii) heat challenge (increasing from 18 to 30 °C), and (iii) cold challenge (decreasing from 18 to 4 °C) after which host gene expression was profiled. Cold challenged corals elicited widespread differential expression, however, there were no differences between symbiotic phenotypes. In contrast, brown colonies exhibited greater gene expression plasticity under heat challenge, including enrichment of cell cycle pathways involved in controlling photobiont growth. While this plasticity was greater, the genes driving this plasticity were not associated with an amplified environmental stress response (ESR) and instead showed patterns of a dampened ESR under heat challenge. This provides nuance to the oxidative bleaching hypothesis and suggests that, at least during the early onset of bleaching, photobionts reduce the host's ESR under elevated temperatures in A. poculata.

Turbulent blood flow in a cerebral artery with an aneurysm.

Unruptured intracranial aneurysms are common in the general population, and many uncertainties remain when predicting rupture risks and treatment outcomes. One of the cutting-edge tools used to investigate this condition is computational fluid dynamics (CFD). However, CFD is not yet mature enough to guide the clinical management of this disease. In addition, recent studies have reported significant flow instabilities when refined numerical methods are used. Questions remain as to how to properly simulate and evaluate this flow, and whether these instabilities are really turbulence. The purpose of the present study is to evaluate the impact of the simulation setup on the results and investigate the occurrence of turbulence in a cerebral artery with an aneurysm. For this purpose, direct numerical simulations were performed with up to 200 cardiac cycles and with data sampling rates of up to 100,000 times per cardiac cycle. Through phase-averaging or triple decomposition, the contributions of turbulence and of laminar pulsatile waves to the velocity, pressure and wall shear stress fluctuations were distinguished. For example, the commonly used oscillatory shear index was found to be closely related to the laminar waves introduced at the inlet, rather than turbulence. The turbulence energy cascade was evaluated through energy spectrum estimates, revealing that, despite the low flow rates and Reynolds number, the flow is turbulent near the aneurysm. Phase-averaging was shown to be an approach that can help researchers better understand this flow, although the results are highly dependent on simulation setup and post-processing choices.

[Prediction of risk of in-hospital death in patients with chronic heart failure complicated by lung infections using interpretable machine learning].

OBJECTIVE: To predict the risk of in-hospital death in patients with chronic heart failure (CHF) complicated by lung infections using interpretable machine learning. METHODS: The clinical data of 1415 patients diagnosed with CHF complicated by lung infections were obtained from the MIMIC-IV database. According to the pathogen type, the patients were categorized into bacterial pneumonia and non-bacterial pneumonia groups, and their risks of in-hospital death were compared using Kaplan-Meier survival curves. Univariate analysis and LASSO regression were used to select the features for constructing LR, AdaBoost, XGBoost, and LightGBM models, and their performance was compared in terms of accuracy, precision, F1 value, and AUC. External validation of the models was performed using the data from eICU-CRD database. SHAP algorithm was applied for interpretive analysis of XGBoost model. RESULTS: Among the 4 constructed models, the XGBoost model showed the highest accuracy and F1 value for predicting the risk of in-hospital death in CHF patients with lung infections in the training set. In the external test set, the XGBoost model had an AUC of 0.691 (95% CI: 0.654-0.720) in bacterial pneumonia group and an AUC of 0.725 (95% CI: 0.577-0.782) in non-bacterial pneumonia group, and showed better predictive ability and stability than the other models. CONCLUSION: The overall performance of the XGBoost model is superior to the other 3 models for predicting the risk of in-hospital death in CHF patients with lung infections. The SHAP algorithm provides a clear interpretation of the model to facilitate decision-making in clinical settings.

[Epidemiological characteristics and drug resistance of diarrheagenic Escherichia coli infection in diarrhea patients in Shanghai, 2016-2022].

Objective: To understand the infection status, epidemiological characteristics and drug resistance of Diarrheagenic Escherichia coli (DEC) in Shanghai and provide evidence for the disease surveillance. Methods: The epidemiological data of diarrhea cases in Shanghai from 2016 to 2022 were collected from Shanghai Diarrhea Comprehensive Surveillance System, and stool samples were collected from the cases for DEC detection. The drug resistance data was obtained from Chinese Pathogen Identification Network. Statistical analysis was conducted by using χ2 and fisher test. Results: In 24 883 diarrhea cases detected during 2016-2022, the DEC positive rate was 9.13% (2 271/24 883), the single DEC positive rate was 8.83% (2 197/24 883) and the mixed DEC positive rate was 0.30% (74/24 883). The main type of DEC was Enterotoxigenic Escherichia coli (ETEC) [4.33% (1 077/24 883)]. The DEC positive rate was highest in people aged ≤5 years 18.48% (22/119). The annual peak of DEC positive rate was observed during July - September [5.91% (1 470/24 883)]. The DEC positive rate were 9.47% (554/5 847) and 9.02% (1 717/19 036) in urban area and in suburbs, respectively, Enteroaggregative Escherichia coli (EAEC) [3.98% (233/5 847)] and ETEC [4.56% (868/19 036)] were mainly detected. From 2016 to 2019, the DEC positive rate was 9.42% (1 821/19 330), while it was 8.10% (450/5 553) from 2020 to 2022, the main DEC types were ETEC (4.87%, 941/19 330) and EAEC (4.70%, 261/5 553). The multi-drug resistance rate was 40.21% (618/1 537). The top three antibiotics with high drug resistance rates were ampicillin [64.74% (995/1 537)], nalidixic acid [58.49% (899/1 537)] and tetracycline [45.09% (693/1 537)]. Conclusions: Compared with 2016- 2019, a decrease in DEC detection rate was observed during 2020-2022, and the main type of DEC detected shifted from ETEC to EAEC. The prevalence of multi-drug resistance was severe. Therefore, it is necessary to further strengthen the surveillance for DEC drug resistance and standardize the use of clinical antibiotics.

[Prevalence and epidemiological characteristics of major chronic diseases in people living with HIV in Taizhou, Zhejiang Province, 1998-2022].

Objective: To understand the prevalence of major chronic diseases of diabetes, cardiovascular disease and malignant tumor in people living with HIV in Taizhou. Methods: The data were collected from China Information System for Disease Control and Prevention and Taizhou Chronic Disease Information Management System. A total of 5 126 people living HIV under follow-up in Taizhou from 1998 to 2022 were included in the analysis. Software SAS 9.4 was used for χ2 test, trend analysis and logistic regression analysis. Results: In the 5 126 people living with HIV, the reported prevalence rates of diabetes,cardiovascular disease and malignant tumor were 10.28% (527/5 126),3.98% (204/5 126) and 6.01% (308/5 126), respectively. 37.00% (195/527) and 48.58% (256/527), 40.20% (82/204) and 48.53% (99/204), 37.66% (116/308) and 48.38% (149/308) were diagnosed as diabetes, cardiovascular disease and malignant tumor before and after confirmation of HIV infection. From 2013 to 2022, the proportion of HIV infected people diagnosed with diabetes, cardiovascular disease and malignant tumor after confirmation increased (trend χ2=79.98,P<0.001; trend χ2=17.44,P<0.001; trend χ2=32.06,P<0.001). Based on the analysis on the factors for complicated chronic diseases in people living with HIV, it was found that women under 60 years old (aOR=0.66, 95%CI: 0.50-0.86) and those with access to antiviral treatment for >5 years before 2016 (aOR=0.54,95%CI:0.37-0.78) were less likely to develop complicated chronic diseases, and those under 60 years old with initial CD4+T lymphocytes counts <200 cells/µl (aOR=1.32, 95%CI: 1.02-1.70), those aged 40-49 and 50-59 years (aOR=2.88, 95%CI:2.20-3.79; aOR=5.43, 95%CI: 4.10-7.21) as well as those without a record of treatment medication use after 2016 (aOR=1.95,95%CI:1.20-3.16) were more likely to develop complicated chronic diseases. The probability of developing complicated chronic diseases might increase with age in people living with HIV. Conclusions: From 1998 to 2022, there was a certain proportion of complicated chronic diseases among HIV infected individuals in Taizhou, and the proportion of diagnosed cases increased after HIV infection was confirmed. It is necessary to conduct early chronic disease screening, behavior intervention and standardized management in people living with HIV.

[Development of a prediction model for incidence of diabetic foot in patients with type 2 diabetes and its application based on a local health data platform].

Objective: To construct a diabetes foot prediction model for adult patients with type 2 diabetes based on retrospective cohort study using data from a regional health data platform. Methods: Using Yinzhou Health Information Platform of Ningbo, adult patients with newly diagnosed type 2 diabetes from January 1, 2015 to December 31, 2022 were included in this study and divided randomly the train and test sets according to the ratio of 7∶3. LASSO regression model and bidirectional stepwise regression model were used to identify risk factors, and model comparisons were conducted with net reclassification index, integrated discrimination improvement and concordance index. Univariate and multivariate Cox proportional hazard regression models were constructed, and a nomogram plot was drawn. Area under the curve (AUC) was calculated as a discriminant evaluation indicator for model validation test its calibration ability, and calibration curves were drawn to test its calibration ability. Results: No significant difference existed between LASSO regression model and bidirectional stepwise regression model, but the better bidirectional stepwise regression model was selected as the final model. The risk factors included age of onset, gender, hemoglobin A1c, estimated glomerular filtration rate, taking angiotensin receptor blocker and smoking history. AUC values (95%CI) of risk outcome prediction at year 5 and 7 were 0.700 (0.650-0.749) and 0.715(0.668-0.762) for the train set and 0.738 (0.667-0.801) and 0.723 (0.663-0.783) for the test set, respectively. The calibration curves were close to the ideal curve, and the model discrimination and calibration powers were both good. Conclusions: This study established a convenient prediction model for diabetic foot and classified the risk levels. The model has strong interpretability, good discrimination power, and satisfactory calibration and can be used to predict the incidence of diabetes foot in adult patients with type 2 diabetes to provide a basis for self-assessment and clinical prediction of diabetic foot disease risk.

[Effect of preoperative immune checkpoint inhibitors on reducing residual lymph node metastases in patients with gastric cancer: a retrospective study].

Objective: To investigate the effect of immune checkpoint inhibitors on reducing residual lymph node metastasis in patients with gastric cancer. Methods: The cohort of this retrospective study comprised patients from Nanfang Hospital of Southern Medical University and the First Affiliated Hospital of Xiamen University who had undergone systemic treatment prior to gastrectomy with D2 lymphadenectomy and had achieved Grade 1 primary tumor regression (TRG1) from January 2014 to December 2023. After exclusion of patients who had undergone preoperative radiotherapy, data of 58 patients (Nanfang Hospital: 46; First Affiliated Hospital of Xiamen University: 12) were analyzed. These patients were allocated to preoperative chemotherapy (Chemotherapy group, N=36 cases) and preoperative immunotherapy plus chemotherapy groups (Immunotherapy group, N=22 cases). There were no significant differences between these groups in sex, age, body mass index, diabetes, tumor location, pathological type, Lauren classification, tumor differentiation, pretreatment depth of invasion by primary tumor, pretreatment lymph node stage, pretreatment clinical stage, mismatch repair protein status, number of preoperative treatment cycles, or duration of preoperative treatment (all P>0.05). The primary outcome measure was postoperative lymph node downstaging. Secondary outcomes included postoperative depth of invasion by tumor, number of lymph nodes examined, and factors affecting residual lymph node metastasis status. Results: Lymph node downstaging was achieved significantly more often in the Immunotherapy group than the Chemotherapy group (pN0: 90.9% [20/22] vs. 61.1% [22/36]; pN1: 4.5% [1/22] vs. 36.1% [13/36]; pN2: 4.5% [1/22) vs. 0; pN3: 0 vs. 2.8% [1/36], Z=-2.315, P=0.021). There were no significant difference between the two groups in number of lymph nodes examined (40.5±16.3 vs. 40.8±17.5, t=0.076, P=0.940) or postoperative depth of invasion by primary tumor (pT1a: 50.0% [11/22] vs. 30.6% [11/36]; pT1b: 13.6% [3/22] vs. 19.4% [7/36]; pT2: 13.6% [3/22] vs. 13.9% [5/36]; pT3: 13.6% [3/22] vs. 25.0% [9/36]; pT4a: 9.1% [2/22] vs. 11.1% [4/36], Z=-1.331, P=0.183). Univariate analysis revealed that both preoperative treatment regimens were associated with residual lymph node metastasis status in patients whose primary tumor regression was TRG1 (χ2=6.070, P=0.014). Multivariate analysis incorporated the following factors: pretreatment depth of invasion by primary tumor, pretreatment lymph node stage, pretreatment clinical stage, number of preoperative treatment cycles, and preoperative treatment duration. We found that a combination of immunotherapy and chemotherapy administered preoperatively was an independent protective factor for reducing residual lymph node metastases in study patients whose primary tumor regression was TRG1 (OR=0.147, 95%CI: 0.026-0.828, P=0.030). Conclusion: Compared with preoperative chemotherapy alone, a combination of preoperative immunotherapy and chemotherapy achieved greater reduction of residual lymph node metastases in the study patients who achieved TRG1 tumor regression in their primary lesions.

Triptolide and its pro-drug Minnelide target high-risk MYC amplified medulloblastoma in preclinical models.

Most children with medulloblastoma (MB) achieve remission, but some face very aggressive metastatic tumors. Their dismal outcome highlights the critical need to advance therapeutic approaches that benefit such high-risk patients. Minnelide, a clinically relevant analog of the natural product triptolide, has oncostatic activity in both preclinical and early clinical settings. Despite its efficacy and tolerable toxicity, this compound has not been evaluated in MB. Utilizing a bioinformatic dataset that integrates cellular drug response data with gene expression, we predicted that Group 3 (G3) MB, which has a poor five-year survival, would be sensitive to triptolide/Minnelide. We subsequently showed that both triptolide and Minnelide attenuate the viability of G3 MB cells ex vivo. Transcriptomic analyses identified MYC signaling, a pathologically relevant driver of G3 MB, as a downstream target of this class of drugs. We validated this MYC dependency in G3 MB cells and showed that triptolide exerts its efficacy by reducing both MYC transcription and MYC protein stability. Importantly, Minnelide acted on MYC to reduce tumor growth and leptomeningeal spread, which resulted in improved survival of G3 MB animal models. Moreover, Minnelide improved the efficacy of adjuvant chemotherapy, further highlighting its potential for the treatment of MYC-driven G3 MB patients.

Diabetes and long duration leading to speech-, low/mid-, and high- frequency hearing loss: current evidence from the China National Health Survey 2023.

PURPOSE: To examine the effect of diabetes, duration of diabetes, and blood glucose on speech-, low/mid-, and high-frequency hearing loss. METHODS: In this cross-sectional study, 2821 participants aged 20-87 years in the China National Health Survey were included. Diabetes was defined as valid fasting blood glucose (FBG) of ≥ 7.0 mmol/L, a self-reported history of diabetes or the use of anti-diabetic medications. Speech-(500, 1000, 2000, and 4000 Hz), low/mid- (500, 1000 and 2000 Hz), and high-frequency (4000, 6000, and 8000 Hz) hearing loss was defined as pure tone average of responding frequencies > 20 dB HL in the better ear, respectively. RESULTS: In fully adjusted models, for speech-, low/mid-, and high-frequency hearing loss, compared with no diabetes, those with diabetes (OR[95%CI]: 1.44 [1.12, 1.86], 1.23 [0.94, 1.61], and 1.75 [1.28, 2.41], respectively) and with diabetes for > 5 years duration (OR[95%CI]: 1.63 [1.09, 2.42], and 1.63 [1.12, 2.36], 2.15 [1.25, 3.70], respectively) were at higher risk. High FBG level was associated with a higher risk of speech-, low/ mid-, and high-frequency hearing loss. And there were stronger associations between HL and diabetes, longer duration and higher in "healthier population" (no hypertension, no dyslipidemia and younger age). CONCLUSION: Diabetes, longer duration, and higher FBG level were independently associated with hearing loss for speech-, low/mid- and high-frequency hearing loss, particularly in higher frequency and "healthier population". Paying more attention to hearing loss in those populations could lower the burden of hearing loss.

Cortisol secretion autonomy associated with weight loss outcome after laparoscopic sleeve gastrectomy: a prospective cohort study in Asian patients.

OBJECTIVE: Laparoscopic sleeve gastrectomy (LSG) is a widely recognized effective bariatric surgery. However, variable weight loss outcomes post-surgery remained a clinical challenge. Currently, there is no established consensus on the factors influencing weight loss failure following LSG. This study aimed to explore the association between preoperative cortisol secretion autonomy and postoperative weight loss in obese patients undergoing LSG. PATIENTS AND METHODS: A cohort of 181 patients with simple obesity (BMI ≥ 28 kg/m2) who underwent LSG and were followed up for one year was analyzed. Weight loss was measured by the percentage of excess weight loss (%EWL), and cortisol secretion autonomy was evaluated using a 1 mg dexamethasone suppression test (DST). Regression models were used to analyze the correlation between preoperative 1 mg DST results and %EWL one year after laparoscopic sleeve gastrectomy (LSG). RESULTS: Cortisol secretion autonomy was significantly lower in the %EWL ≥ 75% group and higher in the %EWL < 75% group, showing a negative correlation with %EWL (R = -0.336, p = 0.001). Logistic regression analysis indicated that high cortisol secretion autonomy was significantly correlated with %EWL < 75% after LSG. The likelihood of %EWL being < 75% was 10.47 times greater in patients with high cortisol secretion autonomy compared to those with low cortisol secretion autonomy (odds ratio 10.472, confidence interval: 1.660-66.048, p = 0.012). CONCLUSIONS: Cortisol secretion autonomy emerges as an independent predictor of weight loss outcomes in Asian patients undergoing LSG. This finding suggests the potential for cortisol secretion autonomy to inform preoperative assessments and personalized treatment strategies in bariatric surgery.