The impact of the host microbiota on Candida albicans infection.

The human microbiota is a complex microbial ecosystem populated by bacteria, fungi, viruses, protists, and archaea. The coexistence of fungi alongside with many billions of bacteria, especially in the gut, involves complex interactions, ranging from antagonistic to beneficial, between the members of these two kingdoms. Bacteria can impact fungi through various means, such as physical interactions, secretion of metabolites, or alteration of the host immune response, thereby affecting fungal growth and virulence. This review summarizes recent progress in this field, delving into the latest understandings of bacterial-fungal-immune interactions and innovative therapeutic approaches addressing the challenges of treating fungal infections associated with microbiota imbalances.

[Research progress on the driving factors and mechanisms of antimicrobial resistance production and spread from the perspective of One Health].

Antimicrobial resistance poses a serious threat to public health and is one of the major challenges worldwide. As global social, economic, and environmental changes lead to increased exposure of populations to antimicrobials, the antimicrobial resistance of pathogens has accelerated and resulted in weakened clinical infection treatment effects. This article reviews the main mechanisms and driving factors of the production and spread of antimicrobial resistance from the perspective of "One Health"and discusses methods and strategies for controlling antimicrobial resistance from multiple dimensions. It also looks forward to the prospects of research and prevention of drug resistance to explore antimicrobial resistance prevention and control strategies based on "One Health".

[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.

[Advances in the use of bevacizumab for the treatment of respiratory papilloma].

Respiratory papilloma is a relatively common benign tumor of the respiratory tract, and a few patients may develop malignant changes. The disease has an insidious onset and lacks specific clinical manifestations, and its manifestations are closely related to the growth mode, location and size of the tumor. It can involve multiple parts, such as the larynx, trachea, bronchus, and lung parenchyma, which cause coughing, hoarseness, dysphonia, and, in severe cases, may lead to obstruction of the respiratory tract. At present, the treatment of respiratory papilloma lacks standardization, and there is no effective method to cure the disease. Surgery remains the main treatment for alleviating patients' symptoms and preventing airway obstruction. However, due to the high recurrence rate of respiratory papilloma, multiple surgeries are often needed, which reduces the quality of life of patients and increases their disease burden and economic burden. Bevacizumab, a vascular endothelial growth factor-binding antibody inhibitor, is a promising adjuvant treatment modality that shows good potential for reducing symptoms and the frequency of surgery. This article aimed to review the efficacy and safety of bevacizumab for the treatment of respiratory papilloma and discuss the differences and efficacy of the systemic application and intralesional injection of bevacizumab for the treatment of respiratory papilloma.

[Research progress on detection techniques for effective albumin concentration].

Hypoalbuminemia is one of the important clinical features of decompensated cirrhosis. As the disease progresses, not only does the total albumin concentration decrease, but so does the proportion of albumin that remains structurally and functionally intact. The structural and functional integrity of albumin is essential for its normal physiological role in the body. This led to the concept of "effective albumin concentration," which may be much lower than the total albumin concentration routinely measured clinically in patients with advanced cirrhosis. Liquid chromatography-tandem mass spectrometry, and electron paramagnetic resonance (EMR) are emerging technologies for effective albumin concentration detection, showing promising clinical application prospects, but research in patients with cirrhosis is still in the preliminary stage. Therefore, this article will comprehensively summarize the latest research on the aspects of effective albumin detection methods, liquid chromatography-tandem mass spectrometry, and electron paramagnetic resonance, as well as their applications.

Adoptive transfer of personalized neoantigen-reactive TCR-transduced T cells in metastatic colorectal cancer: phase 2 trial interim results.

Adoptive cell transfer (ACT) with neoantigen-reactive T lymphocytes can mediate cancer regression. Here we isolated unique, personalized, neoantigen-reactive T cell receptors (TCRs) from tumor-infiltrating lymphocytes of patients with metastatic gastrointestinal cancers and incorporated the TCR α and ß chains into gamma retroviral vectors. We transduced autologous peripheral blood lymphocytes and adoptively transferred these cells into patients after lymphodepleting chemotherapy. In a phase 2 single-arm study, we treated seven patients with metastatic, mismatch repair-proficient colorectal cancers who had progressive disease following multiple previous therapies. The primary end point of the study was the objective response rate as measured using RECIST 1.1, and the secondary end points were safety and tolerability. There was no prespecified interim analysis defined in this study. Three patients had objective clinical responses by RECIST criteria including regressions of metastases to the liver, lungs and lymph nodes lasting 4 to 7 months. All patients received T cell populations containing ≥50% TCR-transduced cells, and all T cell populations were polyfunctional in that they secreted IFNγ, GM-CSF, IL-2 and granzyme B specifically in response to mutant peptides compared with wild-type counterparts. TCR-transduced cells were detected in the peripheral blood of five patients, including the three responders, at levels ≥10% of CD3+ cells 1 month post-ACT. In one patient who responded to therapy, ~20% of CD3+ peripheral blood lymphocytes expressed transduced TCRs more than 2 years after treatment. This study provides early results suggesting that ACT with T cells genetically modified to express personalized neoantigen-reactive TCRs can be tolerated and can mediate tumor regression in patients with metastatic colorectal cancers. ClinicalTrials.gov registration: NCT03412877 .

[Epidemiological and etiological characteristics of herpes pharyngitis in 3 prefectures in Jiangsu Province].

Objective: To analyze the epidemiological and etiological characteristics of herpes pharyngitis (HA) in three prefectures of Jiangsu Province, and provide evidence for the prevention and control of HA in Jiangsu. Methods: Three surveillance sentinel hospitals in Wuxi, Suzhou and Yancheng were selected from May 2018 to December 2022, and information related to HA visits and hospitalized cases was regularly collected from the hospital inpatient management system by age groups. Enterovirus nucleic acid detection was performed by RT-PCR, and sequencing analysis, identification of genotype subtypes, and phylogenetic analysis were performed on the sequences of the gene encoding the coat protein VP1 of the main prevalent strains. Results: A total of 57 709 HA cases were recorded in the sentinel hospitals in in Wuxi, Suzhou and Yancheng, which was 1.76 times higher than the reported cases of hand, foot and mouth disease during the same period (57 709/32 831).The percentage of HA hospitalizations was 1.35% (781/57 709), and the percentage of hospitalizations showed an increasing trend from year to year (χ2=62.79, P<0.001 ).The incidence peak of HA was during May-July. The cases were mainly children aged 12-59 months (67.07%, 38 708/57 709), with the highest case number in age group 36-59 months (34.40%, 19 852/57 709). The HA positivity rate was 33.82% (644/1 904); enterovirus A was predominant (54.04%, 348/644); of these, Coxsackievirus (CV)A6 accounted for the highest percentage (52.59%, 183/348), while CVA16 and CVA4 accounted for 24.71% (86/348) and 15.23% (53/348), respectively. All 10 CVA4 HA endemic strains belonged to the C2 gene subtype, and all 6 CVA6 HA endemic strains belonged to the D3a gene subtype; and were genetically closer to and related to the strains in some areas of China (Fujian Province, Guangzhou City, Jiangxi Province, Yunnan Province, Tianjin City, etc.). Conclusions: The disease burden of HA was heavy in 3 areas in Jiangsu, children in age group 12-59-month were mainly affected, and the annual incidence peak of HA was during May-July. The pathogens causing HA varied, but predominated by enterovirus A and had low intra-typical differentiation, and no new evolutionary branches were found, suggesting that it is necessary to include HA in foot and mouth disease surveillance or regarded as a notifiable communicable disease.

[High expression of the stemness-associated molecule Nanog in esophageal squamous cell carcinoma tissues promotes tumor invasion and metastasis by activating the TGF-ß signaling pathway].

OBJECTIVE: To investigate the expression of Nanog and its regulatory relationship with MMP-2/MMP-9 proteins in esophageal squamous cell carcinoma (ESCC). METHODS: We detected Nanog and MMP-2/MMP-9 protein expressions in 127 ESCC tissues and 82 adjacent normal tissues using immunohistochemistry and explored their correlations with the clinicopathological parameters and prognosis of the patients. GEO database was utilized to analyze the pathways enriched with the stemness-related molecules including Nanog, and TIMER online tool was used to analyze the correlations among TßR1, MMP-2, and MMP-9 in esophageal cancer. RESULTS: Nanog and MMP-2/MMP-9 proteins were significantly upregulated in ESCC tissues and positively intercorrelated. Their expression levels were closely correlated with infiltration depth and lymph node metastasis of ESCC but not with age, gender, or tumor differentiation. The patients with high expressions of Nanog and MMP-2/MMP-9 had significantly shorter survival time. Bioinformatics analysis showed enrichment of stemness-associated molecules in the TGF-ß signaling pathway, and the expressions of MMP-2/MMP-9 and TßR1 were positively correlated. In cultured ESCC cells, Nanog knockdown significantly decreased the expression of TßR1, p-Smad2/3, MMP-2, and MMP-9 and strongly inhibited cell migration. CONCLUSION: The high expressions of Nanog, MMP-2, and MMP-9, which are positively correlated, are closely related with invasion depth, lymph node metastasis, and prognosis of ESCC. Nanog regulates the expressions of MMP-2/MMP-9 proteins through the TGF-ß signaling pathway, and its high expression promotes migration of ESCC cells.

High-throughput combination assay for studying biofilm formation of uropathogenic Escherichia coli.

Uropathogenic Escherichia coli, the most common cause for urinary tract infections, forms biofilm enhancing its antibiotic resistance. To assess the effects of compounds on biofilm formation of uropathogenic Escherichia coli UMN026 strain, a high-throughput combination assay using resazurin followed by crystal violet staining was optimized for 384-well microplate. Optimized assay parameters included, for example, resazurin and crystal violet concentrations, and incubation time for readouts. For the assay validation, quality parameters Z' factor, coefficient of variation, signal-to-noise, and signal-to-background were calculated. Microplate uniformity, signal variability, edge well effects, and fold shift were also assessed. Finally, a screening with known antibacterial compounds was conducted to evaluate the assay performance. The best conditions found were achieved by using 12 µg/mL resazurin for 150 min and 0.023% crystal violet. This assay was able to detect compounds displaying antibiofilm activity against UMN026 strain at sub-inhibitory concentrations, in terms of metabolic activity and/or biomass.

Burden of gastrointestinal cancers among people younger than 50 years in China, 1990 to 2019.

OBJECTIVES: This study aimed to assess the burden of early-onset gastrointestinal (GI) cancers in China over three decades. STUDY DESIGN: A comprehensive analysis was performed using data from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019. METHODS: Data on early-onset GI cancers in 2020 and from 1990 to 2019 were extracted from GLOBOCAN 2020 database and GBD 2019, respectively. The average annual percent change (AAPC) was calculated to analyze the temporal trends using the Joinpoint Regression Program. The Bayesian age-period-cohort (BAPC) model was used to predict future trends up to 2030. RESULTS: In China, there were 185,980 incident cases and 119,116 deaths of early-onset GI cancer in 2020, with the highest incidence and mortality observed in liver cancer (new cases: 71,662; deaths: 62,412). The spectrum of early-onset GI cancers in China has transitioned over the last 30 years. The age-standardized rates of incidence, mortality, and disability-adjusted life years for colorectal and pancreatic cancers exhibited rapid increases (AAPC >0, P ≤ 0.001). The fastest-growing incidence rate was found in colorectal cancer (AAPC: 3.06, P < 0.001). Despite the decreases in liver, gastric, and esophageal cancers, these trends have been reversed or flattened in recent years. High body mass index was found to be the fastest-growing risk factor for early-onset GI cancers (estimated annual percentage change: 2.75-4.19, P < 0.05). Projection analyses showed an increasing trend in age-standardized incidence rates for almost all early-onset GI cancers during 2020-2030. CONCLUSIONS: The transitioning pattern of early-onset GI cancers in China emphasizes the urgency of addressing this public health challenge.

[Epidemiological and clinical characteristics of respiratory syncytial virus infection among people aged 60 and above in Beijing City].

Objective: To investigate the epidemiological and clinical characteristics of RSV among patients aged ≥60 years in Beijing from 2015 to 2023. Methods: Based on the respiratory pathogen surveillance system, samples of upper respiratory tract infections (URTI), non-severe community-acquired pneumonia (nsCAP) and severe community-acquired pneumonia (sCAP) among people aged ≥60 years were collected from 28 sentinel hospitals in 16 districts of Beijing from January 2015 to December 2023. Swab samples were collected from URTI within one week, and lower respiratory tract samples from nsCAP and sCAP were collected. Demographic and epidemiological data were also collected. Various respiratory pathogens including RSV were detected. Results: From January 2015 to December 2023, a total of 20 349 cases of acute respiratory infections aged ≥60 years were included, with the RSV-positive rate of 1.54% (313/20 349, 95%CI: 1.39%-1.68%). Among them, the total RSV-positive rates of older people during the pre-pandemic, pandemic, and post-pandemic periods of COVID-19 were 1.59% (207/13 006, 95%CI: 1.38%-1.81%), 0.82% (38/4 650, 95%CI: 0.56%-1.08%) and 2.53% (68/2 693, 95%CI: 1.93%-3.12%), respectively. The difference in RSV-positive rate was statistically significant (P<0.001). Based on the sampling time of cases, the RSV epidemic season for older people in Beijing was from October to March of the following year, with a peak period in December or January of the following year. In the post COVID-19 pandemic, there were very few RSV-positive cases detected in the elderly from April to June 2023, with only one positive case detected in May and one in June. The RSV-positive rate of older people increased significantly from October to December, reaching 11.75% (51/383) in December. Among 263 RSV-positive cases in the elderly, RSV-A, RSV-B and unclassified type accounted for 43.35% (114/263), 29.28% (77/263) and 27.38% (72/263), respectively. Since 2020, there has been a subtype conversion, with RSV-B being the main focus. Among 197 elderly cases that have complete clinical data, the main symptoms were cough (86.8%, 171/197), sputum (80.2%, 158/197) and fever (73.60%, 145/197). About 24.87% (49/197) of elderly cases experienced complications. The hospitalization mortality rate was 4.57% (9/197), and the hospitalization rate was 78.68% (155/197). The ICU occupancy rate was 1.99% (36/197). The mechanical ventilation usage rate was 13.32% (33/197), and the length of hospital stay [M (Q1, Q3)] was 12 (9, 16) days. Conclusion: In Beijing, the RSV infection rate is relatively low during the COVID-19 pandemic, and the prevalence of COVID-19 is relatively high. In 2023, there was no out-of-season outbreak of RSV infection among the elderly. Elderly RSV infection cases have multiple complications, severe diseases, and poor prognosis.

[Circ_0000263 improves radiosensitivity of Hela cells by inhibiting the activity of telomerase protein through miR-338-3p/TERT].

Objective: To explore the effect and molecular mechanism of circ_0000263 on HeLa cell activity, apoptosis, telomerase activity, and radiosensitivity. Methods: The Hela cells were divided into si-NC, si-circ, vector, circ_0000263, anti-NC, anti-miR-338-3p, miR-NC, miR-338-3p, si-circ+anti-NC, si-circ+ anti-miR-338-3p, si-circ+vector, si-circ+TERT, sh-NC, sh-circ groups. Reverse transcription-quantitative real-time polymerase chain reaction (RT-qPCR) was used to detect the expressions of circ_0000263 and miR-338-3p. Cell clone formation array was used to detect cell survival; cell counting kit-8 (CCK-8) to detect cell proliferation; flow cytometry to detect apoptosis; western blot method to detect the expressions of proliferating cell nuclear antigen (PCNA), Cleaved-casp3, telomerase reverse transcriptase (TERT) proteins; double luciferase assay to detect the targeting relationships of circ_0000263 and miR-338-3p, miR-338-3p and TERT; telomere repeat amplification enzyme linked immunosorbent assay (TRAR-ELISA) to detect telomerase activity. Results: Circ_0000263 was highly expressed in Hela cells, miR-338-3p was low expressed, and TERT was highly expressed; circ_0000263 was also highly expressed in Hela cells treated with radiation (P＜0.05). Knockdown of circ_0000263 inhibited the clone formation and cell proliferation ability of HeLa cells, and enhanced the radiosensitivity and apoptosis of HeLa cells. In contrast, knockdown of circ_0000263 decreased PCNA protein expression level and enhanced Cleaved-casp3 protein expression level in HeLa cells (P＜0.05). The apoptosis rate in the si-circ group was (13.19±1.12)%, which was higher than (6.80±0.62)% of si-NC group (P＜0.05). The apoptosis rate in the si-circ+4 Gy group was (24.82±1.57)%, which was higher than (17.00±0.96)% of si-NC+4 Gy group (P＜0.05). Circ_0000263 targeted regulated miR-338-3p, and miR-338-3p targeted regulated TERT. MiR-338-3p was lowly expressed in HeLa cells, and knockdown of circ_0000263 elevated miR-338-3p expression level in HeLa cells. Circ_0000263 regulated TERT expression and inhibited telomerase activity through miR-338-3p. MiR-338-3p/TERT can restore the effect of circ_0000263 on the radiosensitivity of Hela cells. The apoptosis rate in the si-circ+anti-NC group was (27.37±0.89)%, which was higher than (18.22±1.18)% of the si-circ+anti-miR-338-3p group (P＜0.05). The apoptosis rate in the si-circ+vector group was (27.55±0.48)%, which was higher than (20.10±0.68)% of si-circ+TERT group (P＜0.05). After 72 hours of radiation by 4 Gy, the cell survival fraction of si-circ+anti-NC group was 0.41±0.02, which was lower than 0.66±0.03 of the si-circ+anti-miR-338-3p group (P＜0.05); the cell survival fraction of si-circ+vector group was 0.42±0.05, which was lower than 0.70±0.03 of si-circ+TERT group (P＜0.05). Conclusion: Inhibiting the expression of circ_0000263 supresses the proliferation of Hela cells by regulating miR-338-3p/TERT, promotes apoptosis, inhibits telomerase activity, increases the radiosensitivity of cancer cells, and provides a theoretical basis for improving the radiosensitivity of Hela cells.

[Early experience with mechanical hemodynamic support for catheter ablation of malignant ventricular tachycardia].

Objective: To explore the role of mechanical hemodynamic support (MHS) in mapping and catheter ablation of patients with hemodynamically unstable ventricular tachycardia (VT), report single-center experience in a cohort of consecutive patients receiving VT ablation during MHS therapy, and provide evidence-based medical evidence for clinical practice. Methods: This was a retrospective cohort study. Patients with hemodynamically unstable VT who underwent catheter ablation with MHS at Beijing Anzhen Hospital, Capital Medical University between August 2021 and December 2023 were included. Patients were divided into rescue group and preventive group according to the purpose of treatment. Their demographic data, periprocedural details, and clinical outcomes were collected and analyzed. Results: A total of 15 patients with hemodynamically unstable VT were included (8 patients in the rescue group and 7 patients in the preventive group). The acute procedure was successful in all patients. One patient in the rescue group had surgical left ventricular assist device (LVAD) implantation, remaining 14 patients received extracorporeal membrane oxygenation (ECMO) for circulation support. ECMO decannulation was performed in 12 patients due to clinical and hemodynamic stability, of which 6 patients were decannulation immediately after surgery and the remaining patients were decannulation at 2.0 (2.5) d after surgery. Two patients in the rescue group died during the index admission due to refractory heart failure and cerebral hemorrhage. During a median follow-up of 30 d (1 d to 12 months), one patient with LVAD had one episode of ventricular fibrillation at 6 months after discharge, and no further episodes of ventricular fibrillation and/or VT occurred after treatment with antiarrhythmic drugs. No malignant ventricular arrhythmia occurred in the remaining 12 patients who were followed up. Conclusions: MHS contributes to the successful completion of mapping and catheter ablation in patients with hemodynamically unstable VT, providing desirable hemodynamic status for emergency and elective conditions.

[Correlation between coronary artery tortuosity and poor prognosis in patients with septal hypertrophic cardiomyopathy].

Objective: To investigate the incidence of coronary artery tortuosity and its correlation with poor prognosis in patients with septal hypertrophic cardiomyopathy (HCM). Methods: This was a retrospective cohort study. Patients with septal HCM who were hospitalized in Fuwai Central China Cardiovascular Hospital and Zhengzhou University People's Hospital between December 1, 2017 and June 10, 2021 were selected. Non-HCM patients were matched by gender, age, and hypertension as control group. Septal HCM was divided into two groups based on the presence or absence of coronary artery tortuosity. Clinical baseline data and coronary angiography findings were compared using a multifactorial logistic analysis of the risk factors for coronary artery tortuosity. Patients were followed up until July 1, 2022, with the primary outcome being the composite endpoint of malignant arrhythmia, ischemic stroke and all-cause death. Incidence densities were compared between the coronary artery tortuosity and non-coronary artery tortuosity groups of septal HCM patients. The Cox risk-ratio model was used to analyze risk factors for primary outcomes in septal HCM patients. Results: There were 156 patients in the septal HCM group and 156 patients in the control group, both aged (57.0±11.4) years, and 75 (48.1%) were female. The incidence of coronary artery tortuosity was significantly higher in the septal HCM group than in the control group (63.5% vs. 36.5%, P<0.01), and the coronary artery tortuosity score was also higher in the septal HCM group than in the control group (P<0.01). Multiple logistic regression analysis showed that septal HCM was a risk factor for coronary artery tortuosity (OR=3.27, 95%CI: 2.02-5.29, P<0.01). In the septal HCM patients, after (2.5±1.2) years of follow-up, the incidence density of primary outcome was significantly higher in the coronary artery tortuosity group than in the non-coronary artery tortuosity group (P=0.02), while each on-point in coronary artery tortuosity score increased the risk of primary outcome by 53% for septal HCM patients (HR=1.53, 95%CI: 1.26-1.86, P<0.01). Conclusions: Patients with septal HCM are more prone to suffer coronary artery tortuosity and suffer from it to a greater extent. Coronary artery tortuosity is an important risk factor for adverse events in patients with septal HCM.

[A single-center retrospective study of salvage allogeneic hematopoietic stem cell transplantation pretreated with MeCBA regimen for refractory/relapsed acute myeloid leukemia].

Thirty refractory relapsed acute myeloid leukemia (R/R AML) patients who received salvage allo-HSCT with MeCBA conditioning regimen from January 2018 to June 2022 at Henan Cancer Hospital were included, and their clinical data were reviewed. There were 16 males and 14 females among the 30 patients with a median age of 37 (16-53) years. There were 3 sibling allograft donor transplants, 1 unrelated donor transplant, and 26 haplotype transplants. The median course of pre-transplant chemotherapy was 4 (3-22). The time of neutrophil engraftment was 14 (9-22) days and 18 (10-40) days for platelet. The 30-day cumulative incidence of neutrophil engraftment was 100% and the 100-day cumulative incidence of platelet engraftment was 96.7% (95% CI 85.4% -97.5% ). 22 (73.3% ) patients experienced grade 1-2 gastrointestinal reactions, and there was no grade 3-4 organ toxicity. With a median follow-up of 37.1 months, the overall survival (OS) rate, event-free survival (EFS) rate, cumulative recurrence rate (CIR), and non-recurrence mortality (NRM) rate at 3 years after transplantation were 70.0% (95% CI 50.3% -83.1% ), 65.3% (95% CI 44.8% -79.8% ), 21.2% (95% CI 9.2% -44.4% ) and 16.7% (95% CI 7.3% -35.5% ), respectively.

[The association between visceral adipose thickness and gestational diabetes mellitus in the first trimester].

Objective: To investigate the association between visceral adipose tissue (VAT) thickness in early pregnancy and the risk of gestational diabetes mellitus (GDM). Methods: Based on the Qingdao Women and Children Health Cohort, pregnant women in the first trimester (11-13+6 weeks of gestation) were enrolled in this cohort study between May 2019 and October 2022. The VAT was measured in first trimester and determined as the distance from the inner margin of the rectus abdominis muscle to the anterior wall of the great artery using multi-functional color ultrasound. The 75 g oral glucose tolerance test (OGTT) results were followed up at 24-28 weeks and the participants were divided into GDM group and non-GDM group. The pregnant women were divided into 4 groups according to the VAT quartile. Log-binomial model and linear regression model were used to analyze the association between VAT and GDM/blood glucose. Results: A total of 3 686 pregnant women were included in this study, the mean age of participants was (30.56±4.05) years and 722 were diagnosed with GDM, with an incidence of 19.6%. The log-binomial regression model results showed that compared with VAT thickness Q1 (VAT<14.70 mm), the GDM risk in Q3 (21.65≤VAT≤29.69 mm) and Q4 (VAT ≥29.70 mm) increased by 34% [RR(95%CI): 1.34 (1.08-1.67)], and 61% [RR(95%CI): 1.61 (1.30-2.00)], respectively. Among women with gestational age<35 years old, compared with VAT thickness Q1, the risk of GDM increased by 42% in Q3 [RR(95%CI): 1.42 (1.22-1.65)] and 70% [RR(95%CI): 1.70 (1.46-1.98)] in Q4, whereas no associations were found in women with gestational age ≥35 years old (P>0.05). The association between VAT and GDM risk was only found in pregnant women with pre-pregnancy BMI <24.0 kg/m2, and the GDM risk increased by 57% [RR(95%CI): 1.57 (1.22-2.04)] in Q3 and 65% [RR(95%CI): 1.65 (1.24-2.19)] in Q4 compare with Q1. The results of multiple linear regression analysis showed that VAT was positively correlated with fasting blood glucose, 1-hour blood glucose after 75 g OGTT and 2-hours blood glucose after 75 g OGTT (all Pfor trend<0.001). Conclusion: High VAT thickness in early pregnancy is an independent risk factor for GDM, and the GDM risk increases with the raising of VAT depth.

[Analysis of pediatric heart transplantation supported by extracorporeal membrane oxygenation].

Objective: To summarize the clinical characteristics of patients with end-stage heart failure who receive heart transplant under extracorporeal membrane oxygenation (ECMO) support. Methods: The clinical data of 12 pediatric patients who received heart transplant with ECMO support in the Seventh Medical Center of Chinese People's Liberation Army General Hospital and Guangdong Provincial People's Hospital, from January 2019 to December 2023 was collected. The data included sex, age, weight, diagnosis, pre-ECMO lactate level, left ventricular ejection fraction (LVEF), vasoactive-inotropic score (VIS), and preoperative ECMO running time. Surgical data included cold ischemia time of the donor heart, cardiopulmonary bypass time, intraoperative use of immunosuppressant, postoperative use of ECMO, duration of postoperative ECMO, rate of successful weaning from ECMO, and survival discharge rate. The paired t-test was performed to compare cardiac function indices before and after left ventricular decompression. Results: The 12 patients ranged in age from 1.1 to 15.8 years, and weighted from 8 to 63 kg. Ten children were diagnosed with dilated cardiomyopathy, one with myocardial underdensification, and one with a novel heterozygous mutation of the SCN5A gene causing overlap syndrome complicated by fatal arrhythmia. Before ECMO, the lactate ranged from 0.6 to>15.0 mmol/L, the LVEF from 6.5% to 43%, and VIS from 3 to 108. Four patients underwent left ventricular decompression supported by preoperative ECMO, and their pulse pressure was significantly increased after decompression ((17.8±2.1) vs. (9.8±1.5) mmHg, 1 mmHg=0.133 kPa, t=11.31, P=0.001), while there was no apparent change in LVEF ((26.8±4.4)% vs. (24.9±4.9)%, t=1.75, P=0.178). A total of 7 children received a second run of ECMO after surgery and 3 of them successfully weaned off ECMO and survived to discharge. In the entire cohort, 10 were successfully weaned from ECMO and 8 survived to discharge. Conclusions: For children with end-stage heart failure supported by ECMO, left ventricular decompression can significantly improve pulse pressure. These patients will eventually require heart transplantation.

Changes in Rumen Epithelial Morphology and Transcriptome, Rumen Metabolome, and Blood Biochemical Parameters in Lactating Dairy Cows with Subacute Rumen Acidosis Following Rumen Content Transplantation.

Interventions targeting the gut microbiota, such as fecal microbiota transplantation, prove effective in repairing the intestinal barrier and facilitating the recovery of its function and metabolism. However, the regulatory mechanisms governing the remodeling of rumen epithelial morphology and function, rumen metabolism, and host metabolism in cows of subacute ruminal acidosis (SARA) remain poorly understood. Here, we explored the changes in rumen epithelial morphology and transcriptome, rumen metabolome, and blood biochemical parameters in SARA cows following rumen content transplantation (RCT). The entire experiment consisted of 2 periods: the SARA induction period and the RCT period. During the SARA induction period, 12 ruminally cannulated lactating Holstein cows were randomly allocated into 2 groups, fed either a conventional diet [CON; n = 4; 40% concentrate, dry matter (DM) basis] or a high-grain diet (HG; n = 8; 60% concentrate, DM basis). Following the SARA induction period, the RCT period started. The HG cows were randomly assigned to 2 groups: the donor-recipient (DR) group and the self-recipient (SR) group. Rumen contents were entirely removed from both groups before RCT. For the DR group, cows were administered 70% rumen content from the CON cows, paired based on comparable body weight; for the SR group, each cow received 70% self-derived rumen content. The results revealed no significant differences in the thicknesses of the stratum corneum, granulosum, and spinosum/basale layers, as well as the total depth of the epithelium between the SR and DR groups. All these measurements exhibited a decreasing trend and fluctuations over time after the transfer. Notably, these fluctuations tended to stabilize at 13 or 16 d after RCT in the SR group, whereas they tended to stabilize after 8 or 13 d of transfer for the DR group. Transcriptome sequencing revealed that a total of 277 differentially expressed genes (DEGs) were identified between the 2 groups. Enrichment analysis showed that the DEGs were significantly enriched in 11 Gene Ontology biological processes and 14 KEGG pathways. The DEGs corresponding to almost any of these 11 biological process terms and 14 pathways showed mixed up- or downregulation following RCT. Metabolomics analysis indicated that a total of 33 differential metabolites were detected between the SR and DR groups, mainly enriched in 5 key metabolic pathways, including plant polysaccharides and starch degradation, lipid metabolism, amino sugar and nucleotide metabolism, purine metabolism, and Krebs cycle. Among them, the levels of differential metabolites associated with the degradation of plant polysaccharides and starches, metabolism of amino sugars and nucleotides, and purine metabolism pathways were significantly elevated in the DR cows. The results of blood biochemical parameters showed that the triglyceride concentration of the DR cows was increased than that of the SR cows, comparable to the level observed in the CON cows during the SARA induction period. Generally, our findings indicated that RCT facilitated the recovery of rumen epithelial morphological structure but did not promote its function recovery. Moreover, RCT enhanced rumen plant polysaccharide and starch degradation, amino sugar and nucleotide sugar metabolism, as well as purine metabolism. Additionally, it further promoted the recovery of plasma metabolites related to lipid metabolism.