OBJECTIVE To explore the effectiveness, potential mechanism and compatibility characteristics of efficacy groups of Dunhuang medical prescription Daxiefei decoction in preventing and treating pneumonia based on chemical bioinformatics method. METHODS To study the effect of Daxiefei decoction freeze-dried powder solution on the proliferation activity of lung epithelial cells through cell experiments. Daxiefei decoction was divided into three groups: clearing away heat group, resolving phlegm group, and nourishing Yin group according to its efficacy characteristics. The chemical components of Daxiefei decoction were obtained by TCMSP database and literature search, and the targets were predicted in Swiss Target Prediction database. Pneumonia disease targets were obtained by DrugBank, TTD, Genecards and DisGeNET databases. STRING database and Cytoscape were used to construct the intersection target interaction network and "drug-component-target- pathway" network and DAVID database was used for KEGG pathway enrichment analysis. The network was used to analyze the scientific connotation of the compatibility of efficacy groups. Furthermore, molecular docking was used to evaluate the target-compound affinity and molecular dynamics was used to explore the dynamic molecular mechanism. RESULTS Cell experiments showed that Daxiefei decoction can maintain the proliferation of lung epithelial cells, reverse the decrease of mitochondrial activity induced by LPS and reduce apoptosis. Complex network analysis showed that the pathways enriched by the three functional groups contained in Daxiefei decoction were mainly distributed in two modules: inflammation regulation and reducing airway mucus hypersecretion. Each module was connected by a common target gene and had its own focus. The results of molecular docking showed that the components quercetin, baicalein, isorhamnetin etc. might be the effective multi-target components of Daxiefei decoction. SRC, EGFR, PPARA etc. had good affinity with each potential active component, which might be a potential target of Daxiefei decoction for preventing and treating pneumonia. Molecular dynamics simulation showed that the potential active component quercetin formed stable intermolecular interactions with SRC. CONCLUSION This study initially reveal the material basis and molecular mechanism of Daxiefei decoction in the prevention and treatment of pneumonia. It also explores the scientific connotation of Daxiefei decoction in the prevention and treatment of pneumonia with different efficacy groups, and its modern development and clinical application provide chemical bioinformatics basis.

Objective:To analyze the influencing factors of skull base reconstruction failure after endoscopic endonasal skull base surgery (EESBS).Methods:A retrospective analysis was performed on 228 EESBS cases at the Affiliated Hospital of Qingdao University from 2018 to 2023. The clinical features associated with skull base reconstruction and postoperative cerebrospinal fluid leakage were collected and analyzed. Lasso regression was initially used for exploratory analysis, and risk factors for reconstruction failure were subsequently evaluated using multifactorial logistic regression.Results:A total of 157 cases of EESBS were included, with an overall reconstruction failure rate of 11.5% (18/157). No patients who underwent second-stage reconstruction with a tipped mucosal flap or multilayered free mucosal and fascial repair experienced further postoperative cerebrospinal fluid leakage. Variables identified through Lasso regression included history of surgery, history of radiotherapy, and site of leakage. Multifactorial logistic analysis showed that history of radiotherapy ( OR=5.96, P=0.021) and site of leakage in the posterior skull base ( OR=8.70, P=0.003) were significant risk factors for failure of skull base reconstruction. Conclusion:In cases with a history of radiotherapy and/or posterior skull base lesions in the operative area, reconstruction strategies should be strengthened to improve the success rate of one-stage repair, in particular, when intraoperative cerebrospinal fluid leakage occurs.

Background Some occupational asthma patients have a high risk of poor prognosis, and early assessment and screening of the high-risk groups with poor prognosis are crucial. Objective To evaluate the prognostic value of serum histone deacetylase 2 (HDAC2) and soluble suppression of tumorigenicity 2 (sST2) in occupational asthma patients. Methods An occupational asthma group containing 100 occupational asthma patients admitted to Baodi District People's Hospital of Tianjin between March 2020 and March 2023 were divided into a mild group of 38 cases, a moderate group of 40 cases, and a severe group of 22 cases, and re-divided into a good prognosis group of 66 cases and a poor prognosis group of 34 cases. During the same period, 98 ordinary asthma patients were recruited as the ordinary asthma group and 98 healthy individuals as the healthy control group. A multivariate logistic regression analysis was performed to investigate the relationships of prognosis with HDAC2, sST2, patients separated from allergen after diagnosis, age, body mass index (BMI), gender, smoking history, years of work, family history of asthma, allergy history, good medication adherence, regular follow-up visits. Receiver operating characteristic (ROC) curve was used to evaluate potential predictive value of serum HDAC2 and sST2, and Z-test was used to compare the area under the curve (AUC). Results The serum HDAC2 concentration [(11.13±2.26) ng·L⁻¹] in the occupational asthma group was lower than that in the ordinary asthma group and the healthy control group [(16.72±3.15), (22.75±4.92) ng·L⁻¹], while the sST2 concentration [(16.64±3.47) ng·L⁻¹] in the occupational asthma group was lower than that in the ordinary asthma group and the healthy control group [(12.49±2.31), (9.04±1.98) ng·L⁻¹] (F=256.623, 201.091; P<0.05). The serum HDAC2 concentration [(7.60±1.67) ng·L⁻¹] in the severe group was lower than that in the moderate and the mild groups [(10.02±2.35), (14.34±3.88) ng·L⁻¹], while the sST2 concentration [(24.65±6.31) ng·L⁻¹] in the severe group was lower than that in the moderate and the mild groups [(16.88±3.50), (11.75±3.09) ng·L⁻¹](F=41.731, 67.564; P<0.05). The serum HDAC2 and the proportion of patients separated from allergen after diagnosis in the poor prognosis group were lower than those in the good prognosis group [(8.19±1.94) vs (12.64±3.29) ng·L⁻¹, 64.71% vs 93.94%], and the serum sST2 in the poor prognosis group was higher than that in the good prognosis group [(21.67±5.86) vs (14.05±3.62) ng·L⁻¹] (t/χ²=7.253, 12.177, 8.020; P<0.05). HDAC2 and sST2 were associated with poor 6-month prognosis in the occupational asthma patients (P<0.05). The AUCs for predicting poor prognosis in the occupational asthma patients by serum HDAC2 and sST2 concentrations alone and in combination were 0.826, 0.838, and 0.902, respectively. Conclusion The serum HDAC2 concentration decreases and the sST2 concentration increases in patients with occupational asthma, and these two indicators may have important predictive value for poor disease prognosis.

Hip fracture is considered as the most severe osteoporotic fracture characterized by high disability and mortality in the elderly. Improved surgical techniques and multidisciplinary team play an active role in alleviating prognosis, which places higher demands on perioperative nursing. Dysfunction, complications, and secondary impact of anaesthesia and surgery add more difficulties to clinical nursing. Besides, there still lack clinical practices in perioperative nursing for elderly patients with hip fracture in China. In this context, led by the Orthopedic Nursing Committee of Chinese Nursing Association, the Expert consensus on clinical practice in perioperative nursing for elderly patients with hip fracture ( version 2023) is developed based on the evidence-based medicine. This consensus provides 11 recommendations on elderly patients with hip fracture from aspects of perioperative health education, condition monitoring and inspection, complication risk assessment and prevention, and rehabilitation, in order to provide guiding advices for clinical practice, improve the quality of nursing and ameliorate the prognosis of elderly patients with hip fracture.

Pulmonary hypertension (PH) is an insidious pulmonary vasculopathy with high mortality and morbidity and its underlying pathogenesis is still poorly delineated. The hyperproliferation and apoptosis resistance of pulmonary artery smooth muscle cells (PASMCs) contributes to pulmonary vascular remodeling in pulmonary hypertension, which is closely linked to the downregulation of fork-head box transcriptional factor O1 (FoxO1) and apoptotic protein caspase 3 (Cas-3). Here, PA-targeted co-delivery of a FoxO1 stimulus (paclitaxel, PTX) and Cas-3 was exploited to alleviate monocrotaline-induced pulmonary hypertension. The co-delivery system is prepared by loading the active protein on paclitaxel-crystal nanoparticles, followed by a glucuronic acid coating to target the glucose transporter-1 on the PASMCs. The co-loaded system (170 nm) circulates in the blood over time, accumulates in the lung, effectively targets the PAs, and profoundly regresses the remodeling of pulmonary arteries and improves hemodynamics, leading to a decrease in pulmonary arterial pressure and Fulton's index. Our mechanistic studies suggest that the targeted co-delivery system alleviates experimental pulmonary hypertension primarily via the regression of PASMC proliferation by inhibiting cell cycle progression and promoting apoptosis. Taken together, this targeted co-delivery approach offers a promising avenue to target PAs and cure the intractable vasculopathy in pulmonary hypertension.

INTRODUCTION: Sepsis is defined as a life-threatening complication that occurs when the body responds to an infection attacking the host. Sepsis rapidly progresses and patients deteriorate and develop septic shock, with multiple organ failure, if not promptly treated. Currently no effective therapy is available for sepsis; therefore, early diagnosis is crucial to decrease the high mortality rate. Genome-wide expression analyses of patients in critical conditions have confirmed that the expression levels of the majority of genes are changed, suggesting that the molecular basis of sepsis is at the gene level. This review aims to elucidate the role of circular (circ) RNAs in the pathogenesis of sepsis and sepsis-induced organ damage. In addition, the feasibility of using circRNAs as novel diagnostic biomarkers for sepsis is also discussed, as well as circRNA-based therapy. METHOD: This narrative review is based on a literature search using Medline database. Search terms used were "circular RNAs and sepsis", "circRNAs and sepsis", "non-coding RNAs and sepsis", "ncRNAs and sepsis", "circRNAs and septic pathogenesis", "circRNAs and septic model", "circRNAs and septic shock" and "circRNAs, biomarker, and sepsis". RESULTS: Numerous studies indicate that circRNAs might exert pivotal roles in regulating the immune system of the host against various pathogens, such as bacteria and viruses. Dysregulation of circRNA expression levels has been confirmed as an early event in sepsis and associated with the inflammatory response, immunosuppression and coagulation dysfunction. This impairment in regulation eventually leads to multiple organ dysfunctions, including of the kidneys, lungs and heart. CONCLUSION By investigating the regulation of circRNAs in sepsis, new molecular targets for the diagnosis and intervention of sepsis can be identified. Such an understanding will be important for the development of therapeutic drugs.
Biomarkers ; Humans ; RNA, Circular ; Shock, Septic/genetics*

Genomic studies of cancer cell alterations,such as mutations,copy number variations(CNVs),and translocations,greatly promote our understanding of the genesis and development of cancers.However,the 3D genome architecture of cancers remains less studied due to the complexity of cancer genomes and technical difficulties.To explore the 3D genome structure in clin-ical lung cancer,we performed Hi-C experiments using paired normal and tumor cells harvested from patients with lung cancer,combining with RNA sequenceing analysis.We demonstrated the feasibility of studying 3D genome of clinical lung cancer samples with a small number of cells(1×104),compared the genome architecture between clinical samples and cell lines of lung cancer,and identified conserved and changed spatial chromatin structures between normal and cancer sam-ples.We also showed that Hi-C data can be used to infer CNVs and point mutations in cancer.By integrating those different types of cancer alterations,we showed significant associations between CNVs,3D genome,and gene expression.We propose that 3D genome mediates the effects of cancer genomic alterations on gene expression through altering regulatory chromatin structures.Our study highlights the importance of analyzing 3D genomes of clinical cancer samples in addition to cancer cell lines and provides an integrative genomic analysis pipeline for future larger-scale studies in lung cancer and other cancers.

The clinical data of 7 patients with porokeratosis (PK) were analyzed retrospectively.In 7 PK patients, 4 cases were disseminated superficial actinic porokeratosis (DSAP),1 case was disseminated superficial porokeratosis (DSP),1 case was giant porokeratosis (GP) and 1 case was hypertrophic porokeratosis (HP).The characteristic cutaneous manifestations were annular well-circumscribed keratotic plaques with slightly atrophic center and elevated border.All patients shared a common histological hallmark, the cornoid lamella.Four cases of DSAP patients had family medical history, consistent with autosomal dominant inheritance.DSP, GP and HP patients denied family medical history.Diagnosis of PK should be based on clinical manifestations, family medical history and histopathological examination.

OBJECTIVE:To establish a method for simultaneous determination of 6 residual organic solvents in aprepitant raw material as methanol,ethanol,acetone,isopropyl alcohol,methyl tert-butyl ether and tetrahydrofuran.METHODS:Headspace capillary gas chromatography was adopted.The determination was performed on DB-624 capillary column using temperature programming.The temperature of injector port was 180 ℃,and flame ionization detector was used with temperature of 260 ℃.Nitrogen was used as carrier gas with flow rate 3.0 mL/min.The spilt ratio was 5 ∶ 1,and head-space injection volume was 1.0 mL.The head-space equilibrium temperature was set at 80 ℃,and equilibrium time was 40 min.RESULTS:The linear ranges of methanol,ethanol,acetone,isopropyl alcohol,methyl tert-butyl ether,tetrahydrofuran were 6.052-605.232 μ g/mL (r=0.999 9),9.987-998.718 μg/mL(r=0.999 9),9.998-999.768 μg/mL(r=0.999 8),9.986-998.634 μg/mL(r=0.999 9),9.991-999.090 μg/mL (r=0.999 7),1.461-146.133 μg/mL(r=0.999 5),respectively.The limits of quantitation were 1.782 1,2.079 0,0.749 8,1.777 8,0.223 1,0.607 0 μg/mL;the limits of detection were 0.594 0,0.693 0,0.249 9,0.592 6,0.074 4,0.202 3 μg/mL,respectively.RSD of precision test was lower than 2.0％.Only acetone and isopropyl alcohol were detected in stability test and reproducibility tests,RSD＜2.0％.Their recoveries were 99.34-100.75％ (RSD=0.52％,n=9),98.20％-100.24％ (RSD=0.69％,n=9),98.07％-100.07％ (RSD=0.84％,n=9),99.86％-101.32％ (RSD=0.58％,n=9),97.87％-104.02％ (RSD=2.13％,n=9),98.26 ％-100.58 ％ (RSD =0.75 ％,n =9),respectively.CONCLUSIONS:The established method is simple,accurate and reproducible,and can be used for simultaneous determination of 6 residual organic solvents in aprepitant raw material.

Objective To investigate the correlation between serum lipoprotein (a) (Lp(a)) level andischemic stroke and its etiological subtypes. Methods The consecutive inpatients with acute ischemic stroke (case group) and age-and sex-matched healthy subjects (control group) over the same period were enrolled retrospectively. The demographic and baseline clinical data, as well as fasting blood glucose, fibrinogen,homocysteine, total cholesterol, triacylglycerol, high-densitylipoprotein cholesterol, low -density lipoprotein cholesterol, and Lp(a) concentration of the case group and the control group were collected. According to TOAST classification criteria, the patients in the case group were divided into large artery atherosclerosis (LAA), small artery occlusion (SAO) and cardioembolism (CE), and the patients with other determined etiology and undetermined etiology were excluded. Multivariate logistic regression analysis was used to make clear the correlation between serum Lp(a) and acute ischemic stroke and its etiological subtypes. Results A total of 214 patients with ischemic stroke were enrolled. Ninety-seven had LAA (45.33%), 64 (29.91%) had SAO, and 53 (24.77%) had CE. There were 118 subjects in the control group. There were significant differences in the proportions of hypertension, diabetes, hyperlipidemia, atrial fibrillation and alcohol consumption, as well as systolic blood pressure, diastolic blood pressure, fasting blood glucose, total cholesterol, low -density lipoprotein cholesterol, Lp(a), fibrinogen, and homocysteine between the case group and the control group (all P <0.001). Multivariate logistic regression analysis showed that after adjustment for age and sex, Lp(a) is an independent risk factor for ischemic stroke (odds ratio [OR] 2.014, 95% confidence interval [CI ] 1.273-3.092, P = 0.036). The independent risk factors for LAA included hypertension (OR 3.353, 95% CI 1.714-6.558, P = 0.001), systolic blood pressure ( OR 2.786, 95% CI 1.136-5.538, P =0.016), homocysteine ( OR 1.108, 95% CI 1.031-2.191, P = 0.005), total cholesterol (OR 2.169, 95% CI 1.599-4.943, P = 0.001), low -density lipoprotein cholesterol ( OR2.782, 95% CI 1.093-5.238, P =0.024), and Lp(a) (OR 3.072, 95% CI 1.907-8.064, P =0.001). Theindependent risk factors for SAO included hypertension ( OR 7.042, 95% CI 3.189-25.55, P =0.001), diabetes mellitus (OR 5.162, 95% CI 2.372-11.23, P =0.001), fibrinogen (OR 1.667, 95% CI 1.434-2.025, P = 0.045), and homocysteine (OR 1.967, 95% CI 1.859-1.995, P =0.036). The independent risk factors for CE included atrial fibrillation (OR 13.340, 95% CI 4.637-39.20, P = 0.001), fibrinogen (OR 2.365, 95% CI 1.147- 4.904, P =0.029), and Lp(a) (OR 1.656, 95% CI 1.996-3.001, P = 0.035). Conclusions Lp(a) is an independent risk factor for ischemic stroke, and can be used as a serum biomarker for predicting the risk of the onset of ischemic stroke. There are differences in independent risk factors between the different stroke etiological subtypes. Lp(a) is independently associated with LAA and CE; however, it has no independent correlation with SAO.