OBJECTIVES: To study the molecular mechanisms of LDH-loaded si-NEAT1 for regulating paclitaxel resistance and tumor-associated macrophage (TAM) polarization in breast cancer. METHODS: qRT-PCR and Western blotting were used to detect the expression of lncRNA NEAT1, miR-133b, and PD-L1 in breast cancer SKBR3 cells and paclitaxel-resistant SKBR3 cells (SKBR3-PR). The effects of transfection with si-NEAT1 and miR-133b mimics on MRP, MCRP and PD-L1 expressions and cell proliferation, migration and apoptosis were investigated using qRT-PCR, Western blotting, scratch and Transwell assays, and flow cytometry. Rescue experiments were conducted using si-NEAT1 and miR-133b inhibitor. Human THP-1 macrophages were cultured in the presence of conditioned media (CM) derived from SKBR3 and SKBR3-PR cells with or with si-NEAT1 transfection for comparison of IL-4-induced macrophage polarization by detecting the surface markers. LDH@si-NEAT1 nanocarriers were constructed, and their effects on MRP, MCRP and PD-L1 expressions and cell behaviors of the tumor cells were examined. THP-1 cells were treated with the CM from LDH@si-NEAT1-treated tumor cells, and the changes in their polarization were assessed. RESULTS: SKBR3-PR cells showered significantly upregulated NEAT1 and PD-L1 expressions and lowered miR-133b expression as compared with their parental cells. Transfection with si-NEAT1 and miR-133b mimics inhibited viability, promoted apoptosis and enhanced MRP and BCRP expressions in SKBR3-PR cells. NEAT1 knockdown obvious upregulated miR-133b and downregulated PD-L1, MRP and BCRP expressions. The CM from SKBR3-PR cells obviously promoted M2 polarization of THP-1 macrophages, which was significantly inhibited by CM from si-NEAT1-transfected cells. Treatment with LDH@si-NEAT1 effectively inhibited migration and invasion, promoted apoptosis, and reduced MRP, BCRP and PD-L1 expressions in the tumor cells. The CM from LDH@si-NEAT1-treated SKBR3-PR cells significantly downregulated Arg-1, CD163, IL-10, and PD-L1 and upregulated miR-133b expression in THP-1 macrophages. CONCLUSIONS LDH@si-NEAT1 reduces paclitaxel resistance of breast cancer cells and inhibits TAM polarization by targeting the miR-133b/PD-L1 axis.
Humans ; MicroRNAs/genetics* ; RNA, Long Noncoding/genetics* ; Paclitaxel/pharmacology* ; Breast Neoplasms/metabolism* ; Drug Resistance, Neoplasm ; B7-H1 Antigen/metabolism* ; Cell Line, Tumor ; Female ; Tumor-Associated Macrophages ; Apoptosis ; Cell Proliferation ; Macrophages ; Cell Movement

Objective:In critical care medicine, extubation is a pivotal step in the management of mechanically ventilated patients. Accurately determining the optimal timing for extubation is essential for minimizing complications and improving patient survival rates. However, reliable indicators to predict clinical outcomes following extubation remain scarce. This study aims to identify a novel and robust predictor of extubation success in critically ill patients, thereby providing clinicians with more precise decision-making support.Methods:This retrospective study analyzed data from adult patients who underwent mechanical ventilation and were evaluated for extubation across six intensive care units (ICUs) at Xiangya Third Hospital of Central South University between January 2019 and December 2021. Patients with a history of difficult airway, upper airway obstruction, or neuromuscular disorders affecting respiratory function were excluded. The primary outcome was the reintubation rate within 24 hours post-extubation. Categorical variables were analyzed using the chi-square test or Fisher’s exact test, while between-group differences were assessed with the Mann-Whitney U test. Significant predictors identified in univariate analysis were further evaluated via multivariate logistic regression. The diagnostic accuracy of the maximum inspiratory pressure/body mass index (MIP/BMI) ratio was determined using receiver operating characteristic (ROC) curve analysis, with the Youden index employed to establish the optimal cutoff value. Kaplan-Meier analysis and log-rank tests were used to compare extubation success rates between groups. Statistical analyses were performed using SPSS V28.0 and Stata v.16.0. Results:Diabetes comorbidity ( OR: 8.181, 95% CI: 1.659–40.338) and MIP/BMI ( OR: 0.140, 95% CI: 0.042–0.469) were identified as independent predictors of reintubation. The area under the ROC curve (AUROC) for MIP/BMI was 0.753, demonstrating good predictive accuracy. The optimal cutoff value for MIP/BMI was 1.26 cmH 2O/(kg·m 2), with a sensitivity of 55.3% and specificity of 92.3%. Kaplan-Meier analysis revealed a significantly higher reintubation rate in the low MIP/BMI group compared to the high MIP/BMI group ( P = 0.009), further validating its predictive utility. Conclusions:This study establishes MIP/BMI as a novel and clinically valuable predictor of extubation outcomes in critically ill patients. A cutoff value of 1.26 cmH 2O/(kg·m 2) was found to best predict successful extubation.

OBJECTIVES: Pelvic floor sensory training is commonly used in clinical practice for the treatment of stress urinary incontinence (SUI); however, there is a lack of comparative studies evaluating pelvic floor sensation between women with SUI and healthy controls. Additionally, normative data for two-point discrimination thresholds in the female pelvic floor region remain scarce. This study aims to compare the results of 4 sensory tests in the pelvic floor region between women with mild SUI and healthy women, in order to provide reference values for two-point discrimination thresholds in this area. METHODS: From April 1 to October 30, 2023, 108 healthy women [(32.5±3.6) years] and 90 women with mild SUI [(32.9±3.3) years] were recruited from the Third Xiangya Hospital, Central South University. Participants underwent 4 sensory tests in the pelvic floor region: Two-dot discrimination, weight perception, shape recognition, and 9-grid localization. The results were compared between the 2 groups. RESULTS: Compared with healthy women, those with mild SUI had lower sensitivity and higher thresholds in 2-dot discrimination tests in the pelvic floor region (all P<0.001). No significant differences were found between groups in weight perception, shape recognition, or grid localization tests (P>0.05). CONCLUSIONS Women with mild stress urinary incontinence have impaired two-point discrimination ability in the pelvic floor region.
Humans ; Female ; Urinary Incontinence, Stress/physiopathology* ; Pelvic Floor/physiopathology* ; Adult ; Sensory Thresholds/physiology*

Objective:To investigate gender differences in arterial velocity pulse index(AVI), which is an indicator of vascular stiffness, across various age groups.Additionally, the study will also examine the risk factors associated with AVI.Methods:This cross-sectional study enrolled 4311 patients with an average age of 57.8±12.8 years at Jiading Branch of Shanghai First People's Hospital between August 2020 and September 2021.Patients were divided into three groups based on age: young(<45 years old, n=755), middle-aged(45-59 years old, n=1260), and elderly(≥60 years old, n=2 296). The AVI of the subject was obtained using the cuff oscillation wave method.The subject's AVI was acquired using the cuff oscillation wave.High AVI, indicating arteriosclerosis, was defined as AVI≥33.The subjects were then divided into two groups: the high AVI group(122 cases)and the normal AVI group(4 189 cases).Results:The ankle-brachial index(AVI)was found to be 12.8±3.7, 17.5±5.7, and 19.8±6.5 in the young, middle-aged, and elderly groups, respectively.The study revealed that AVI increased with age( Ftrend=767.819, P<0.01). Additionally, the incidence of high AVI in middle-aged women was found to be(2.8% or 20/722), which was higher than that in men 0.9%(5/538)in the same age group.This difference was statistically significant( χ2=5.371, P<0.05). The results of the multivariate logistic regression analysis indicate that being overweight, having a higher height, and a pulse rate greater than 80 BPM are protective factors in preventing a high incidence of AVI.The odds ratios( OR)with 95% confidence intervals( CI)for these factors were 0.468(0.317-0.690), 0.926(0.895-0.958), and 0.143(1.026-2.432), respectively, all with a P-value less than 0.01.On the other hand, old age, systolic blood pressure of 140 mmHg or higher, and diastolic blood pressure of 90 mmHg or higher were identified as risk factors for AVI.The ORs with 95% CIs for these factors were 2.119(1.322-3.396), 6.652(4.136-10.699), and 1.580(1.026-2.432), respectively, all with a P- value less than 0.05l. Conclusions:Arterial stiffness, as measured by the ankle-brachial index(ABI), tends to increase with age.In middle-aged subjects, women have a higher incidence of high ABI than men.Independent risk factors for high ABI include age and increased blood pressure, while factors such as overweight and height may affect the measured value of ABI.

Objective:To understand the prevalence of human parechovirus (HPeV) in neonates of Hunan Provincial People’s Hospital, and analyze genetic evolutionary characteristics.Methods:From June to September 2021, fecal samples of inpatient neonates were collected in Hunan Provincial People′s Hospital. TaqMan real-time qPCR and RT-PCR were used for HPeV screening and genotyping. High-throughput sequencing and PCR were used to obtain whole genomes. Phylogenetic analysis was performed after sequencing.Results:A total of 123 fecal samples of neonates were collected, of which 22 were HPeV positive, with 17.89% positive rate. All the strains belonged to the HPeV-1 genotype. One full-length genomic sequence of 7 269 bp were obtained, and provisionally named Hunan/HPeV/2021, which has the highest nucleotide identity with known HPeV-1 genotype, with 86.6%-91.9% nucleotide identity. The nucleotide and amino acid identity of open reading frame (ORF) with known similar sequences were 90.3%-92.6% and 97.3%-98.3%, respectively. The phylogenetic analysis showed that Hunan/HPeV/2021 belongs to the HPeV-1 genotype, which is clustered into the same clade as the popular HPeV-1 strains in China.Conclusions:HPeV has a high prevalence in inpatient neonates of Hunan Provincial People’s Hospital and belong to the HPeV-1 genotype.

Objective: To investigate the association between body mass index ( BMI ) and mortality risk among older Chinese based on the China Health and Retirement Longitudinal Study ( CHARLS ). Methods: The demographic features, BMI, prevalence of chronic diseases and mortality among the elderly at ages of 60 years and greater were captured from the CHARLS database from 2011 to 2018. A multivariable Cox proportional hazards regression model was used to examine the association between BMI and the risk of death. Results: Totally 6 023 subjects were enrolled, including 3 006 men ( 50.09% ) and 3 017 women ( 49.91% ), and 68.69% of the participants ( 4 137 subjects ) were at ages of 60 to 69 years. There were 637 subjects ( 10.58% ) with underweight, 1 544 ( 25.63% ) with overweight, and 557 ( 9.25% ) with obesity. During the follow-up period ( 35 091 person-years ), 1 035 subjects died. Multivariable Cox proportional hazards regression analysis revealed an increased risk of mortality among the underweight elderly ( HR=1.496, 95%CI: 1.261-1.775 ) and a reduced risk of mortality among the obese elderly ( HR=0.671, 95%CI: 0.511-0.881 ) relative to the elderly with normal weight, after adjustment for age, gender, smoking, household registration, administration of anti-diabetic drugs, administration of anti-dyslipidemia drugs, and administration of anti-hypertensive drugs. Conclusion It is found that the risk of mortality among the Chinese elderly correlatives with BMI through the analysis of CHARLS data.

Objective:To study the clinical characteristics of children with adenovirus pneumonia complicated with liver injury and the understanding of clinicians.Methods:The children diagnosed with community-acquired adenovirus pneumonia were enrolled from January 1, 2013 to December 31, 2020. The clinical characteristics of the normal liver function group and the liver injured group were compared, and multivariate regression was applied.Results:Among the 3 294 enrolled children, 1 704 children had elevated alanine aminotransferase and/or aspartate aminotransferase on admission, and the liver function impairment rate was 51.7% (1 704/3 294), of which 1 671 cases were mildly injured (98.06%, 1 671/1 704), 28 cases were moderately injured (1.64%, 28/1 704), and 5 cases were severely injured (0.29%, 5/1 704). Compared with the normal liver function group, the proportion of male children in the liver injured group was higher (68.1% vs. 64.2%, P=0.017), and the age was younger[16(9, 30) months vs. 38(19, 53) months, P<0.001]. Children with liver injury were more likely to have wheezing (32.9% vs. 18.7%, P<0.001), shortness of breath (13.7% vs. 9.1%, P<0.001), and diarrhea (11.0% vs. 4.7%, P<0.001). The white blood cell counts, neutrophil counts and hemoglobin in the liver injured group were lower than those in the normal group, while the lymphocyte counts were higher than those in the normal group. The levels of creatine kinase, cardiac creatine kinase and lactate dehydrogenase were higher. The proportion of severe pneumonia in the liver injured group (26.9% vs. 11.2%, P<0.001) was higher than that in the normal liver function group, and the case fatality rate was significantly higher (1.47% vs. 0.25%, P<0.001). Comparing the probability of liver injury in children with mild and severe adenovirus pneumonia, it was found that the severe pneumonia group had more frequent liver injury (73.0% vs 46.6%, P<0.001), and both moderate and severe liver injury groups were higher than in the mild group. Further multivariate logistic regression analysis did not find a significant factor associated with the incidence of liver injury. Conclusions:The incidence of adenovirus pneumonia in children with liver injury was high, and mild injury is more common. Children with liver injury were younger, had more severe clinical symptoms such as wheezing and shortness of breath, and higher proportion of severe pneumonia and mortality. Among them, children with severe pneumonia had a higher proportion of liver injury, and moderate to severe injury was more common. The monitoring of children with different degrees of liver injury should be strengthened.

This paper reports 3 cases of acute hepatitis of unknown cause in children who met the case definition of WHO. Human adenovirus group C was detected in case 3, and the quantity of viral DNA was relatively high, which may be related to the liver function damage in the patient, but its role in pathogenesis needs further study to confirm.

Objective:To explore the pathogenic spectrum and epidemiological characteristics of respiratory viruses in children with acute lower respiratory tract infection in Changsha, and provide scientific basis for disease prevention and treatment.Methods:A total of 1 092 respiratory tract specimens of children were collected and 12 respiratory viruses were detected by real-time quantitative transcription polymerase chain reaction.Results:Among the samples from 1 092 cases, those from 437 cases (40%) were positive for respiratory syncytial virus (RSV), 337 cases (30.9%) were positive for parainfluenza virus-3 (PIV-3), 263 cases (24.1%) were positive for human bocavirus (HBOV) and 228 cases (20.8%) were positive for adenovirus (ADV). The detection rates of boys and girls were 82.26% and 83.42%. The infection rate of RSV was higher in the group ≤ 6 months of age, the infection rates of PIV-3 and HBOV ≤2 years old were higher, and the infection rate of ADV was higher in the group between 6 months to 5 years old. The detection rates of virus infection of spring, summer, autumn and winter were 90.48%, 83.50%, 62.26% and 82.80%, respectively, there were significant differences among them.Conclusions:The main viruses in children with acute lower respiratory tract infection in Changsha were RSV and PIV-3. Mixed infections were common. Children under 2 years of age were more likely to get acute lower respiratory infections. Viruses had seasonal trends and peaked in winter and spring.

Objective:To establish an index system of population based SARS-CoV-2 nucleic acid screening, and provide reference to determine the screening coverage appropriately.Methods:The literature review and brain storming sessions were used to develop the basic frame and index system of population based SARS-CoV-2 nucleic acid screening. Based on Delphi method and Analytic Hierarchy Process, 21 domestic experts were selected for two rounds of consultation to determine the index system of population based SARS-CoV-2 nucleic acid screening and its weight.Results:The positive indexes of experts in two rounds of consultations were both 100%. The experts' authority coefficients ( Cr) were 0.88±0.08 and 0.89±0.07, respectively. And the range of coefficient of variation ( CV) were (0.08, 0.24), (0.09, 0.25). The Kendall's W coordination coefficients were 0.34 and 0.22 respectively, which were statistically significant. The index system of population based SARS-CoV-2 nucleic acid screening was established, which had 4 first-level indexes, 11 second-level indexes and 58 third-level indexes. Besides, the weight of each index was determined. Conclusion:The index system of population based SARS-CoV-2 nucleic acid screening has been established, which can provide scientific reference for the health administration to determine the coverage of population based SARS-CoV-2 nucleic acid screening when local COVID-19 epidemic occurs.