OBJECTIVES: To investigate the predictive factors for plastic bronchitis (PB) in children with Mycoplasma pneumoniae pneumonia (MPP) and to establish a nomogram prediction model for PB occurrence. METHODS: A retrospective analysis was conducted on children with MPP hospitalized at The Affiliated Hospital of Xuzhou Medical University from January 2023 to June 2024. The patients were randomly divided into a training set (n=562) and a validation set (n=240) at a ratio of 7:3 using simple random sampling. In the training set, patients were categorized into a PB group (n=70) and a non-PB group (n=492) based on the occurrence of PB. Spearman correlation analysis was performed to exclude collinearity among variables, followed by univariate analysis and LASSO regression to identify predictive factors. A nomogram prediction model for PB in children with MPP was constructed. The discriminative ability of the model was assessed using receiver operating characteristic (ROC) curve analysis, model calibration was evaluated with calibration curves, and clinical utility was appraised through decision curve analysis. RESULTS: Compared with the non-PB group, the PB group exhibited significantly longer disease duration prior to bronchoscopy, prolonged fever duration, higher fever peaks, higher proportions of patients with a family history of allergy and personal allergy history, and a higher proportion of patients with pleural effusion, as well as significantly elevated levels of white blood cell count, neutrophil percentage, C-reactive protein, procalcitonin, fibrinogen, D-dimer, aspartate aminotransferase, alanine aminotransferase, creatine kinase, lactate dehydrogenase, immunoglobulin A, and interleukin-6, along with a significantly lower lymphocyte percentage (all P<0.05). LASSO regression analysis identified pleural effusion, procalcitonin, D-dimer, and lactate dehydrogenase as major predictive factors for PB occurrence in children with MPP. The nomogram model based on these factors demonstrated good discriminative ability (area under the ROC curve: 0.852 in the training set and 0.830 in the validation set), with satisfactory calibration and clinical benefit. CONCLUSIONS The nomogram prediction model based on pleural effusion, procalcitonin, D-dimer, and lactate dehydrogenase provides effective predictive performance for the occurrence of PB in children with MPP.
Humans ; Pneumonia, Mycoplasma/complications* ; Nomograms ; Male ; Female ; Child ; Child, Preschool ; Retrospective Studies ; Bronchitis/etiology* ; Infant ; ROC Curve ; Adolescent

OBJECTIVE: To investigate the inhibitory effect of Tanreqing Injection (TRQ) on the activation of nucleotide-binding oligomerization domain-like receptor pyrin domain containing 3 (NLRP3) inflammasome in macrophages infected with influenza A virus and the underlying mechanism based on mitophagy pathway. METHODS: The inflammatory model of murine macrophage J774A.1 induced by influenza A virus [strain A/Puerto Rico/8/1934 (H1N1), PR8] was constructed and treated by TRQ, while the mitochondria-targeted antioxidant Mito-TEMPO and autophagy specific inhibitor 3-methyladenine (3-MA) were used as controls to intensively study the anti-inflammatory mechanism of TRQ based on mitophagy-mitochondrial reactive oxygen species (mtROS)-NLRP3 inflammasome pathway. The levels of NLRP3, Caspase-1 p20, microtubule-associated protein 1 light chain 3 II (LC3II) and P62 proteins were measured by Western blot. The release of interleukin-1β (IL-1β) was tested by enzyme linked immunosorbent assay, the mtROS level was detected by flow cytometry, and the immunofluorescence and co-localization of LC3 and mitochondria were observed under confocal laser scanning microscopy. RESULTS: Similar to the effect of Mito-TEMPO and contrary to the results of 3-MA treatment, TRQ could significantly reduce the expressions of NLRP3, Caspase-1 p20, and autophagy adaptor P62, promote the expression of autophagy marker LC3II, enhance the mitochondrial fluorescence intensity, and inhibit the release of mtROS and IL-1β (all P<0.01). Moreover, LC3 was co-localized with mitochondria, confirming the type of mitophagy. CONCLUSION TRQ could reduce the level of mtROS by promoting mitophagy in macrophages infected with influenza A virus, thus inhibiting the activation of NLRP3 inflammasome and the release of IL-1β, and attenuating the inflammatory response.
Mitophagy/drug effects* ; NLR Family, Pyrin Domain-Containing 3 Protein/metabolism* ; Animals ; Macrophages/virology* ; Inflammasomes/drug effects* ; Drugs, Chinese Herbal/pharmacology* ; Mice ; Mitochondria/metabolism* ; Reactive Oxygen Species/metabolism* ; Influenza A virus/physiology* ; Interleukin-1beta/metabolism* ; Cell Line ; Injections

OBJECTIVES: To investigate the protective effects of dexmedetomidine (DEX) against heat stress (HS)-induced oncosis in human skeletal muscle cells (HSKMCs) and its underlying mechanisms. METHODS: A HSKMC model of HS-induced oncosis were established by 43 ℃ water bath for 4 h, and the effects of treatments with 30 μmol/L DEX, ML385 (a Nrf2 inhibitor) +DEX, si-Nrf2+HS, and si-Nrf2+DEX prior to modeling on cell viability was assessed using CCK-8 assay. Oncosis characteristics were evaluated using transmission electron microscopy and Annexin V-FITC/PI flow cytometry. The oxidative stress markers (GSH, GSH-Px, MDA, SOD and ROS), mitochondrial membrane potential, energy metabolism, and inflammatory cytokines (TNF-α, IL-6 and IL-1β) in the cells were quantified using standard kits, and the expressions of porimin, caspase-3 and Nrf2 pathway proteins were analyzed using Western blotting and qRT-PCR. RESULTS: HS induced typical oncotic features in HSKMCs including organelle swelling and cytoplasmic vacuolization. DEX pretreatment significantly attenuated these changes, reduced Annexin V⁺/PI⁺ cell ratio and cellular porimin expression, and lowered the levels of ROS and MDA while restoring GSH and SOD levels. DEX pretreatment also significantly increased the mitochondrial membrane potential and ATP level, upregulated the expressions of Nrf2, p-Nrf2, HO-1 and NQO1, and suppressed the expressions of TNF-α, IL-6 and IL-1β. The protective effects of DEX were obviously attenuated by interventions with ML385 or si-Nrf2. CONCLUSIONS DEX mitigates HS-induced HSKMC oncosis by activating the Nrf2/HO-1 pathway to relieve oxidative stress, mitochondrial dysfunction, and inflammatory responses.
Humans ; Dexmedetomidine/pharmacology* ; NF-E2-Related Factor 2/metabolism* ; Oxidative Stress/drug effects* ; Heat-Shock Response/drug effects* ; Signal Transduction/drug effects* ; Membrane Potential, Mitochondrial ; Muscle, Skeletal/cytology* ; Heme Oxygenase-1/metabolism* ; Apoptosis/drug effects*

The structure of intestinal tissue is complex. In vitro simulation of intestinal structure and function is important for studying intestinal development and diseases. Recently, organoids have been successfully constructed and they have come to play an important role in biomedical research. Organoids are miniaturized three-dimensional (3D) organs, derived from stem cells, which mimic the structure, cell types, and physiological functions of an organ, making them robust models for biomedical research. Intestinal organoids are 3D micro-organs derived from intestinal stem cells or pluripotent stem cells that can successfully simulate the complex structure and function of the intestine, thereby providing a valuable platform for intestinal development and disease research. In this article, we review the latest progress in the construction and application of intestinal organoids.
Organoids/cytology* ; Intestines/physiology* ; Humans ; Animals ; Pluripotent Stem Cells

OBJECTIVE: To investigate the relationship between physical activity and genetic risk and their combined effects on the risk of developing chronic obstructive pulmonary disease. METHODS: This prospective cohort study included 318,085 biobank participants from the UK. Physical activity was assessed using the short form of the International Physical Activity Questionnaire. The participants were stratified into low-, intermediate-, and high-genetic-risk groups based on their polygenic risk scores. Multivariate Cox regression models and multiplicative interaction analyses were used. RESULTS: During a median follow-up period of 13 years, 9,209 participants were diagnosed with chronic obstructive pulmonary disease. For low genetic risk, compared to low physical activity, the hazard ratios ( HRs) for moderate and high physical activity were 0.853 (95% confidence interval [ CI]: 0.748-0.972) and 0.831 (95% CI: 0.727-0.950), respectively. For intermediate genetic risk, the HRs were 0.829 (95% CI: 0.758-0.905) and 0.835 (95% CI: 0.764-0.914), respectively. For participants with high genetic risk, the HRs were 0.809 (95% CI: 0.746-0.877) and 0.818 (95% CI: 0.754-0.888), respectively. A significant interaction was observed between genetic risk and physical activity. CONCLUSION Moderate or high levels of physical activity were associated with a lower risk of developing chronic obstructive pulmonary disease across all genetic risk groups, highlighting the need to tailor activity interventions for genetically susceptible individuals.
Humans ; Pulmonary Disease, Chronic Obstructive/epidemiology* ; Exercise ; Male ; Female ; Middle Aged ; Prospective Studies ; Aged ; Genetic Predisposition to Disease ; Risk Factors ; United Kingdom/epidemiology* ; Incidence ; Adult

With the rapid advancement of synthetic biology, CRISPR-Cas systems have emerged as a powerful tool for gene editing, demonstrating significant potential in various fields, including medicine, agriculture, and industrial biotechnology. This review comprehensively summarizes the significant progress in applying artificial intelligence (AI) technologies to the design, mining, and modification of CRISPR-Cas systems. AI technologies, especially machine learning, have revolutionized sgRNA design by analyzing high-throughput sequencing data, thereby improving the editing efficiency and predicting off-target effects with high accuracy. Furthermore, this paper explores the role of AI in sgRNA design and evaluation, highlighting its contributions to the annotation and mining of CRISPR arrays and Cas proteins, as well as its potential for modifying key proteins involved in gene editing. These advancements have not only improved the efficiency and precision of gene editing but also expanded the horizons of genome engineering, paving the way for intelligent and precise genome editing.
CRISPR-Cas Systems/genetics* ; Artificial Intelligence ; Gene Editing/methods* ; RNA, Guide, CRISPR-Cas Systems/genetics* ; Machine Learning ; Humans ; Genetic Engineering/methods* ; Synthetic Biology

Objective China is among the 30 countries with a high burden of tuberculosis(TB)worldwide,and TB remains a public health concern.Kashgar Prefecture in the southern Xinjiang Autonomous Region is considered as one of the highest TB burden regions in China.However,molecular epidemiological studies of Kashgar are lacking. Methods A population-based retrospective study was conducted using whole-genome sequencing(WGS)to determine the characteristics of drug resistance and the transmission patterns. Results A total of 1,668 isolates collected in 2020 were classified into lineages 2(46.0%),3(27.5%),and 4(26.5%).The drug resistance rates revealed by WGS showed that the top three drugs in terms of the resistance rate were isoniazid(7.4%,124/1,668),streptomycin(6.0%,100/1,668),and rifampicin(3.3%,55/1,668).The rate of rifampicin resistance was 1.8%(23/1,290)in the new cases and 9.4%(32/340)in the previously treated cases.Known resistance mutations were detected more frequently in lineage 2 strains than in lineage 3 or 4 strains,respectively:18.6%vs.8.7 or 9%,P<0.001.The estimated proportion of recent transmissions was 25.9%(432/1,668).Multivariate logistic analyses indicated that sex,age,occupation,lineage,and drug resistance were the risk factors for recent transmission.Despite the low rate of drug resistance,drug-resistant strains had a higher risk of recent transmission than the susceptible strains(adjusted odds ratio,1.414;95%CI,1.023-1.954;P = 0.036).Among all patients with drug-resistant tuberculosis(DR-TB),78.4%(171/218)were attributed to the transmission of DR-TB strains. Conclusion Our results suggest that drug-resistant strains are more transmissible than susceptible strains and that transmission is the major driving force of the current DR-TB epidemic in Kashgar.

Objective:To study the effect of first drainage failure on the prognosis of perihilar cholangiocarcinoma (PHCC).Methods:The clinical data of 68 patients with PHCC undergoing surgery in the Department of Pancreatic and Metabolic Surgery of Nanjing Drum Tower Hospital, Affiliated to the Medical School of Nanjing University, from April 2014 to December 2022 were retrospectively analyzed, including 46 males and 22 females, aged (63±9) (range, 39-80) years old. The patients were divided into two groups based on whether the first drainage was successful: successful group ( n=34) and failed group ( n=34). The patient's age, gender, first drainage, complications and other clinical data were collected. Patients were followed up by outpatient or telephone review. Kaplan-Meier method was used for survival analysis, and log-rank test was used for survival comparison. Results:Compared to the successful group, the drainage time [41(28, 52) d vs. 20(14, 28) d], the drainage tube adjustment rate [32.4%(11/34) vs. 0(0/34)], and the incidence of complications after drainage [88.2% (30/34) vs. 0(0/34)] were all increased in the failed group, with the adjustment rate of drainage position decreased [82.4%(28/34) vs. 100%(34/34)] (all P<0.05). Compared to the successful group, the incidence of abdominal infection was higher [70.6%(24/34) vs. 44.1%(15/34)] in the failed group ( P=0.027). The 5-year cumulative survival rates of the failed group and the successful group were 61.4% and 44.1%, respectively ( P>0.05). Conclusion:Compared to the patients of PHCC with first successful drainage, the risk of abdominal infection is increased when first drainage failed, while the incidence of postoperative complications, in-hospital mortality and long-term survival rate are comparable.

Objective To assess the clinical short-term outcomes of implanting D-shant atrial shunt device(aSD)in a single center for patients with heart failure with reduced ejection fraction(HFrEF).Methods From January 2022 to January 2023,a retrospective analysis was conducted on 12 patients with HFrEF who underwent percutaneous implantation of a D-shant aSD.We assessed cardiac chamber size and ventricular function using echocardiography,right heart catheterization measurements and patient clinical indicators were collected,follow up data of 12 months postoperative and pre-implantation D-shant were compared.The primary endpoint of the study was the cumulative occurrence of adverse cardiac,neurologic,or renal events during the follow-up period.Secondary endpoints were improvements in functional status included cardiac function,quality of life,and exercise capacity.Results All 12 patients underwent successful percutaneous inter-atrial shunting procedures using the D-shant.Postoperative immediately fluoroscopy and echocardiography confirmed accurate localization and patency of the atrial shunt devices in all cases.Postoperative hemodynamic assessment revealed a significant decrease in pulmonary capillary wedge pressure[(29.8±3.4)mmHg vs.(17.8±0.8)mmHg,P＜0.001].During 12 months follow-up,the cumulative adverse event rate was 8.3％(one patient received a heart transplant),a significant reduction in left atrial diameter from(65.8±6.5)mm to(48.0±4.5)mm(P＜0.001)was observed.Furthermore,there was notable improvement in clinical cardiac function indices quality of life,and exercise capacity of the patients.Conclusions This single-center retrospective study found that the use of a D-shant aSD to perform percutaneous interatrial shunting in patients with HFrEF is safe and effective.Short-term follow-up demonstrated sustained patency of the shunt and that the intervention was associated with improved functional status.

To investigate the existence of tick-borne pathogens infection of rodents at the border of China and the Demo-cratic People's Republic of Korea(DPRK).PCR was used to detect the spotted fever group rickettsiae(SFGR)ompA gene,Ehrlichia chaffeensis(Ec)and Anaplasma phagocytophilum(Ap)16S rRNA,Candidatus Neoehrlichia mikurensis(CNm)groEL gene,Bartonella(Ba)rpoB gene,and Francisella tularensis(Ft)fopA gene in rodents samples collected from Ji'an of Jilin province and Kuandian of Liaoning Province.The positivity rates of 132 wild rats spleen samples,SFGR,Ec,Ap,CNm,Ba,and Ft were 9.85％,12.88％,5.30％,3.79％,51.52％,and 6.06％,respectively,with statistical differences in in-fection rates(x2=149.236,P=0.000).The infection rate of Ba was the highest in wild rats in this area.There was no signifi-cant difference in the infection rate of SFGR,Ec,Ap,CNm,and Ft among different rats species,but there were significant differences in the infection rate of Ba(x2=13.36,P=0.010).The infection rate of Apodemus agrarius was the highest.A-mong 132 wild rats specimens,the coinfection rate of the two pathogens was 15.9％(21/132),with Ba as the main species(15/132),and two cases of coinfection with three pathogens were detected.The infection of six tick-borne pathogens is common in wild rats at the China/DPRK border.Co-infection of two or three pathogens indicates a risk of multiple tick-borne pathogens and mixed natural foci of multiple tick-borne infec-tious diseases.