ObjectiveTo observe the apoptosis induced by paeoniflorin （PF） in non-small cell lung cancer （NSCLC） cells and explore its mechanism. MethodCell counting kit-8 （CCK-8） was used to detect the inhibition rates of H1299， H292 and A549 cells with different concentrations of PF （2.5， 5， 10， 20， 25 µmol·L^-1）， and to screen suitable concentrations of PF and experimental cells. The inhibitory effect of PF on lung cancer cells was detected by clone formation assay. The effect of PF on cell apoptosis was detected by flow cytometry with annexin V-FITC/propidium iodide （PI） double staining. With the right concentration of drugs， levels of apoptosis-associated protein B-cell lymphoma-2 （Bcl-2）， Bcl-2-associated X protein （Bax）， cleaved Caspase-3 and Caspase-3 were detected by Western blot. At the same time， the molecular expressions of hypoxia inducible factor -1α （HIF-1α） and Hippo signaling pathway were determined. ResultCompared with the blank group， PF significantly inhibited the growth of H1299， H292 and A549 cells of human lung cancer （P<0.01）. PF significantly induced apoptosis in A549 cells （P<0.01）， decreased the Bcl-2/Bax ratio （P<0.01）， and significantly increased the cleaved Caspase-3 expression （P<0.01）. Compared with those in the blank group， the expression levels of HIF-1α， transcriptional coactivator with PDZ-binding motif （TAZ）， large tumor suppressor 1 （LATS1）， Mps one binding 1 （MOB1） and Yes-associated protein （YAP） in A549 cells of the PF treatment group were significantly decreased （P<0.01）， while the expressions of p-LATS1， p-MOB1 and p-YAP were significantly increased （P<0.01）. At the same time， there was no significant effect on the expression levels of phosphorylated mammalian Ste20-like kinase 1 （p-MST1） and MST1， which did not reach a statistical difference. ConclusionAll data demonstrated that PF showed an anti-tumor effect by improving hypoxic conditions and inhibiting the abnormally activated Hippo signaling pathway， thereby inducing and promoting apoptosis in non-small cell lung cancer.

Objective:To construct an artificial intelligence (AI)-assisted system based on deep learning for corneal in vivo confocal microscopy (IVCM) image recognition and to evaluate its value in clinical applications. Methods:A diagnostic study was conducted.A total of 18 860 corneal images were collected from 331 subjects who underwent IVCM examination at Renmin Hospital of Wuhan University and Zhongnan Hospital of Wuhan University from May 2021 to September 2022.The collected images were used for model training and testing after being reviewed and classified by corneal experts.The model design included a low-quality image filtering model, a corneal image diagnosis model, and a 4-layer identification model for corneal epithelium, Bowman membrane, stroma, and endothelium, to initially determine normal and abnormal corneal images and corresponding corneal layers.A human-machine competition was conducted with another 360 database-independent IVCM images to compare the accuracy and time spent on image recognition by three senior ophthalmologists and the AI system.In addition, 8 trainees without IVCM training and with less than three years of clinical experience were selected to recognize the same 360 images without and with model assistance to analyze the effectiveness of model assistance.This study adhered to the Declaration of Helsinki.The study protocol was approved by the Ethics Committee of Renmin Hospital of Wuhan University (No.WDRY2021-K148).Results:The accuracy of this diagnostic model in screening high-quality images was 0.954.Its overall accuracy in identifying normal/abnormal corneal images was 0.916 and 0.896 in the internal and external test sets, respectively.Its accuracy reached 0.983, 0.925 in the internal test sets and 0.988, 0.929 in the external test sets in identifying corneal layers of normal and abnormal images, respectively.In the human-machine competition, the overall recognition accuracy of the model was 0.878, which was similar to the average accuracy of the three senior physicians and was approximately 300 times faster than the experts in recognition speed.Trainees assisted by the system achieved an accuracy of 0.816±0.043 in identifying corneal layers of normal and abnormal images, which was significantly higher than 0.669±0.061 without model assistance ( t=6.304, P<0.001). Conclusions:A deep learning-based assistant system for corneal IVCM image recognition is successfully constructed.This system can discriminate normal/abnormal corneal images and diagnose the corresponding corneal layer of the images, which can improve the efficiency of clinical diagnosis and assist doctors in training and learning.

Long-term care encompasses the effectiveness of life care and health services that are provided to individuals and groups with disabilities,aiming to enhance their physical and mental well-being and overall quality of life.In the context of an aging population,prioritizing long-term care quality for populations with disability becomes imperative.The presenting study examined the main practices of assuring long-term care quality in the United States across 3 critical dimensions of structure,process and outcome,using the Donabedian quality framework theory.The findings were subsequently applied to guide the evaluation of the long-term care quality assurance in China,which serves as a valuable reference for promoting the high-quality development of long-term care services in China.

Objective To investigate the influencing factors of unplanned rehospitalization within one year after surgery among adult renal transplant recipients. Methods The clinical data of 299 recipients who underwent renal transplant surgery in the Department of Organ Transplantation of the Affiliated Hospital of Guizhou Medical University from January 2020 to December 2022 were retrospectively analyzed. The recipients were divided into unplanned rehospitalization group and non-rehospitalization group based on whether they experienced unplanned rehospitalization within one year after surgery. Univariate analysis and binary Logistic regression analysis were performed to explore the influencing factors of unplanned rehospitalization within one year after renal transplantation. Results Among the 299 recipients, 102 experienced unplanned rehospitalization, with an incidence rate of 34.11%. Univariate analysis revealedstatistically significant differences were noted between the two groups in terms of gender, occupational status, preoperative underlying disease, rejection reactions, nosocomial infections, immunosuppressive medication regimens, serum creatinine, cystatin C, serum phosphorus, serum potassium, and initial hospitalization duration (P < 0.05). Binary Logistic regression analysis showed that having ≥3 kinds of preoperative underlying disease (OR=2.122, 95%CI, 1.198 to 3.759) and experiencing rejection reactions (OR=3.162, 95%CI, 1.217 to 8.218) were independent risk factors for unplanned rehospitalization within one year after renal transplantation (P < 0.05). Conclusion The rate of unplanned rehospitalization within one year after surgery is relatively high among adult renal transplant recipients. Having ≥3 preoperative underlying disease and experiencing rejection reactions are independent risk factors for unplanned rehospitalization within one year after surgery. Transplantation healthcare teams can develop corresponding strategies targeting these risk factors to reduce the rate of unplanned rehospitalization and alleviate the burden of disease.

Objective Clarify the basis of the commonly used Tibetan medicinal material"YeGexing",the chemical structure and pharmacological activity were investigated,then provide a basis for standardizing clinical medication,quality control,and rational use of resources.Methods Using literature research;plant taxonomy identification summary of chemical composition investigation and pharmacological activity identification,combined with resource distribution,clinical use status investigation and analysis.Results Tibetan medicine"Yegexing"involved 7 species in 2 families,4 genera,that is Sambucus Linn.from Caprifoliaceae,Senecio L.,Synotis(C.B.Clarke)C.Jeffrey et Y.L.Chen,Saussurea DC.from Compositae.The earliest used"Yegexinggabao"or"white"should be Senecio dianthus.and Senecio solidagineus.in the literature;"Yegexingnabao"or"black"should be Saussurea epilobioides.and Sambucus adnate.;S.raphanifolius.(S.diversifolius.),S.chrysanthemoides.(S.laetus.).S.chinensis.are the main substitutes used in Yunnan,Gansu,and western Sichuan,and are commonly used in the market.YeGexing mainly contains terpenes,flavonoids,alkaloids,phenolic acids and other chemical components;YeGexing black is mainly used for"healing",white is mainly used for"anti-inflammatory",which corresponds to modern pharmacological research on anti-inflammatory,antioxidant,antibacterial and other activities.Conclution In view of the fact that the origin of"Yegexing"involves a variety of plants from different families and genera,"Yegexing"has become a collective name for these plant medicinal materials.According to the lextual results and the research progress on chemical structure and pharmacological activity,from the perspective of conducive to standardizing clinical medication,ensuring efficacy and quality of medicinal materials,its name and variety should be standardized as:"??????(???????????????????/)Yegexinggabao"(that is,the white one),the source is S.dianthus.(S.erythropappa.),S.solidagineus.(S.solidaginea.),S.raphalanifolius.(S.diversifolius.),S.chrysanthemoides.(S.laetus.);"(???????????????????????/)Yegexingnabao"(that is,the black one),the source is S.epilobioides.and S.adnata.and S.chinensis are independent medicines.We should strengthen the investigation of the resources and use status of substitutes in various places,the comparative research on the medicinal material basis and biological activity of different resource species,and standardize their varieties-names-bases to make rational use of their resources.

Objective:To observe the effect of high flow nasal cannula combined with nasopharyngeal airway on improving ventilation in obese patients under general anesthesia without intubation.Methods:A total of 86 obese patients under general anesthesia without intubation admitted to the Lianyungang Hospital of Traditional Chinese Medicine from January to October 2023 were prospectively selected and randomly divided into a control group and an observation group using a random number table method, with 43 cases in each group. The observation group was given high flow nasal cannula combined with nasopharyngeal airway ventilation, while the control group was given ordinary nasal cannula combined with head lifting ventilation. Two groups were compared in terms of perioperative respiratory function, blood gas indicators, hemodynamics, pulse oximetry (SpO 2), and complications. Results:There was a statistically significant difference ( F=7.548, P=0.001; F=7.658, P=0.002) in the final respiratory carbon dioxide pressure (PetCO 2) and oxygenation index (OI) between the two groups with different oxygen flow rates of 2 L/min, 4 L/min, and 6 L/min. The PetCO 2 and OI in the observation group were higher than those in the control group at 4 L/min and 6 L/min, and the difference was statistically significant (all P<0.05). There was a statistically significant difference ( F=10.024, P<0.001; F=10.236, P<0.001) in the oxygen partial pressure (PaO 2) and carbon dioxide partial pressure (PaCO 2) before anesthesia (T 0), 10 minutes after anesthesia (T 1), and at the end of surgery (T 2) between the two groups. The PaO 2 in the observation group was higher than that in the control group at T 1 and T 2, while the PaCO 2 was lower than that in the control group, and the difference was statistically significant (all P<0.001). The difference in mean arterial pressure and heart rate at T 0, T 1, and T 2 time points between the two groups was statistically significant ( F=8.476, P<0.001; F=8.321, P<0.001). The average arterial pressure and heart rate at time points T 1 and T 2 in the observation group were lower than those in the control group, and the difference was statistically significant (all P<0.001). The comparison of SpO 2 at T 0, T 1, and T 2 time points between the two groups showed a statistically significant difference ( F=7.548, P<0.001). The SpO 2 at T 1 and T 2 time points in the observation group was higher than that in the control group, and the difference was statistically significant (all P<0.001). The total incidence of complications in the observation group was lower than that in the control group ( P<0.05). Conclusions:High flow nasal cannula combined with nasopharyngeal airway can significantly improve perioperative respiratory function, blood gas indicators, and SpO 2 in obese patients undergoing general anesthesia without intubation, stabilize hemodynamics, and reduce the risk of complications.

Objective:To determine the carrier frequency and hot-spot variants of a custom-designed expanded carrier screening (ECS) panel with 216 diseases (216-ECS panel) within a Chinese population of childbearing age.Methods:Whole-exome sequencing data from a cohort of 3 097 unrelated healthy individuals (including 1 424 couples) from Peking Union Medical College Hospital between January 2013 and December 2023 were analyzed. Totally 220 genes which inherited in a recessive manner of 216-ECS panel were included in the analysis. The analysis included variant carrier rate, gene carrier rate, cumulative carrier rate, at-risk couple rates, and variant spectrum.Results:(1) Pathogenic variants were identified in 1 472 (47.53%, 1 472/3 097) individuals, with an average of 0.65 pathogenic variants per individual. The rate of at-risk couples was 3.93% (56/1 424). (2) A total of 180 genes were identified, with 16 genes exhibiting a gene carrier rate of ≥1% and 33 genes having a rate of ≥0.5%, most of which were associated with inherited metabolic diseases. Noteworthy genes with higher gene carrier rates and high-frequency variants included GJB2: c.235del, PAH: c.728G>A, ATP7B: c.2333G>T, SLC26A4: c.919-2A>G, GALC: c.1901T>C, POLG: c.2890C>T, SLC22A5: c.1472C>G, USH2A: c.2802T>G, SLC25A13: c.852_855del, GAA: c.761C>T and c.752C>T. Conclusion:This study offers a focused analysis of carrier frequencies and hot-spot variants of 216 diseases of the ECS panel constructed by our laboratory among the Chinese population, laying a foundation for the development of ECS programs tailored to the Chinese population.

Uncovering the risk factors of pulmonary hypertension and its mechanisms is crucial for the prevention and treatment of the disease.In the current study,we showed that experimental periodontitis,which was established by ligation of molars followed by orally smearing subgingival plaques from patients with periodontitis,exacerbated hypoxia-induced pulmonary hypertension in mice.Mechanistically,periodontitis dysregulated the pulmonary microbiota by promoting ectopic colonization and enrichment of oral bacteria in the lungs,contributing to pulmonary infiltration of interferon gamma positive(IFNγ+)T cells and aggravating the progression of pulmonary hypertension.In addition,we identified Prevotella zoogleoformans as the critical periodontitis-associated bacterium driving the exacerbation of pulmonary hypertension by periodontitis,and the exacerbation was potently ameliorated by both cervical lymph node excision and IFNγ neutralizing antibodies.Our study suggests a proof of concept that the combined prevention and treatment of periodontitis and pulmonary hypertension are necessary.

Objective:To carry out clinical and genetic analysis for a child featuring Brain-Lung-Thyroid syndrome (BLTS).Methods:A child who had presented at the Children′s Hospital Affiliated to Shandong University on May 27, 2022 was selected as the study subject. Clinical data was collected. Trio-whole exome sequencing (Trio-WES) was carried out for the child and his parents, and candidate variant was verified by Sanger sequencing and bioinformatic analysis. The child was given individualized treatment following the diagnosis.Results:The child, a two-year-and-seven-month-old boy, had presented with global developmental delay, ataxia and hypothyroidism. WES revealed that he has harbored a heterozygous c. 674C>T variant of the NKX2-1 gene, based on which he was diagnosed with BLTS. CT scan revealed interstitial and parenchymal inflammation in his lungs, which was reduced by budesonide aerosol inhalation. Conclusion:Discovery of the novel c. 674C>T variant has enriched the mutational spectrum of the NKX2-1 gene. Budesonide aerosol may be used to treat lung inflammation associated with BLTS.

Objective:To evaluate the effect of exogenous interleukin-18 (IL-18) binding protein (IL-18BP) on sepsis-associated lung injury and the role of NOD-like receptor family pyrin domain-containing 3 (NLRP3) inflammasomes in rats.Methods:This study was performed in two parts. Experiment Ⅰ Thirty-six SPF-grade healthy male Sprague-Dawley rats, aged 6-8 weeks, weighing 200 g, were allocated into 3 groups ( n=12 each) using a random number table method: sham operation group (S group), sepsis-associated lung injury group (SLI group), and sepsis-associated lung injury+ IL-18BP group (SI group). The rat model of sepsis-associated lung injury was developed using cecal ligation and puncture. The rats in group S underwent laparotomy without the subsequent ligation and puncture procedures. IL-18BP 1.5 mg/kg was intraperitoneally injected immediately after surgery in group SI. Experiment Ⅱ The aforementioned 36 rats were allocated into 3 groups ( n=12 each) using a random number table method: sepsis-associated lung injury + IL-18BP + vehicle group (SIV group), sepsis-associated lung injury + IL-18BP + MCC950 group (SIM group), and sepsis-associated lung injury + IL-18BP + nigericin group (SIN group). In SIV group, SIM group and SIN group, solvent, MCC950 (NLRP3 inhibitor, 5 mg/kg) and nigerin (NLRP3 agonist, 2 mg/kg) were intraperitoneally injected at 30 min before surgery respectively, and IL-18BP 1.5 mg/kg was intraperitoneally injected after operation. HE staining was used to observe the lung injury at 24 h after operation. The left lung tissues were obtained for calculation of the wet/dry weight (W/D) ratio. The concentrations of IL-18 and IL-18BP in broncho-alveolar lavage fluid (BALF) were determined by enzyme-linked immunosorbent assay. The percentage of NLRP3 positive cells in lung tissues was detected by immunofluorescence. The expression of IL-18, IL-18BP, cl-caspase-1 and gasdermin D (GSDMD) in lung tissues was detected by Western blot. Results:Experiment Ⅰ Compared with group S, the injury score of lung tissues, W/D ratio, concentrations of IL-18 and IL-18BP in BALF, and percentage of NLRP3 positive cells were significantly increased, and the expression of IL-18, IL-18BP, cl-caspase-1 and N-GSDMD was up-regulated in group SLI ( P<0.05). Compared with group SLI, the injury score of lung tissues, W/D ratio, concentrations of IL-18 and IL-18BP in BALF, and percentage of NLRP3 positive cells were significantly decreased, the expression of IL-18, cl-caspase-1 and N-GSDMD was down-regulated, and the expression of IL-18BP was up-regulated in group SI ( P<0.05). Experiment Ⅱ Compared with group SIV, the injury score of lung tissues, W/D ratio, concentrations of IL-18 in BALF, and percentage of NLRP3 positive cells were significantly decreased, and the expression of IL-18, cl-caspase-1 and N-GSDMD was down-regulated in group SIM, and the injury score of lung tissues, W/D ratio, concentrations of IL-18 in BALF, and percentage of NLRP3 positive cells were significantly increased, and the expression of IL-18, cl-caspase-1 and N-GSDMD was up-regulated in group SIN ( P<0.05). Conclusions:Exogenous IL-18BP can reduce sepsis-associated lung injury, and the mechanism is related to inhibition of activation of NLRP3 inflammasomes in rats.