Multi-target analgesics with minimal side effects and high efficacy are a key research focus in addressing the global pain crisis. Using a molecular networking approach, five pairs of potent analgesic alkaloid enantiomers were isolated from the roots of Anacyclus pyrethrum (A. pyrethrum). Their structures were elucidated by comprehensive spectroscopic data analysis, including LR-HSQMBC and ¹H-¹⁵N HMBC, quantum ¹³C NMR DP4+ and ECD calculations, and single-crystal X-ray diffraction analysis. Anacyphrethines A (1) and B (2) are highly conjugated and polymethylated 6/6/6/6/5/7/5/5-fused octacyclic tetraazabic alkaloids possessing an unprecedented 8,14,18,24-tetraaza-octacyclo[16.8.2.1^1,23.0^4,28.0^5,17.0^9,16.0^11,15.0^21,27] nonacosane motif. Their biosynthetic pathways are proposed involving key aldol, hydroamination, and Schiff base reactions. All isolates showed potent analgesic effects in vivo. Even at a lower dose of 0.2 mg/kg, (±)-1 and (+)-1 still exhibited more potent analgesic activities than morphine. Interestingly, the racemic mixture (±)-1 showed stronger analgesic effect than either pure enantiomer alone at higher doses of 5 and 1 mg/kg; while, (±)-1 showed significant analgesic activities comparable to (+)-1 at lower doses of 0.2 and 0.04 mg/kg. (+)-1 had stronger analgesic effect than (-)-1 at five tested does. Further tests on 44 analgesic-related targets demonstrated that (+)-1 showed significant inhibitory effects against many ion channels such as TRPM8, Kv1.2, Kv1.3, and Ca_v2.1 with IC₅₀ values of 1.10 ± 0.26, 4.20 ± 0.07, 2.20 ± 0.24, and 10.40 ± 0.69 μmol/L, respectively, while (-)-1 primarily inhibited TRPC6, Kv1.2, and Kv1.3 ion channels with IC₅₀ values of 0.81 ± 0.05, 0.91 ± 0.04, and 1.50 ± 0.13 μmol/L, respectively, without affecting the opioid receptors, suggesting their non-opioid analgesic potentials. The molecular dockings provided structural guidance to develop potent non-opioid analgesics.

Objective To investigate the levels of serum neuregulin-4(NRG4)and serum fatty acid binding protein 4(FABP4)in patients with diabetes retinopathy(DR)and their diagnostic value.Methods From A-pril 2020 to April 2023,a total of 84 DR patients admitted to Endocrine and Metabolic Disease Hospital Affili-ated to Shandong First Medical University were regarded as the observation group.Based on the type of retinal lesions,they were grouped into proliferative lesion group(35 cases)and non proliferative lesion group(49 ca-ses).In addition,84 patients with simple diabetes in the same period were regarded as the NDR group,and 84 healthy people who underwent physical examination in the same period were regarded as the control group.Enzyme linked immunosorbent assay was applied to detect serum levels of NRG4 and FABP4.Multivariate Logistic regression was applied to analyze the influencing factors of DR occurrence.Receiver operating charac-teristic(ROC)curve was applied to analyze the diagnostic value of serum NRG4 and FABP4 levels for DR.Results The levels of C-reactive protein(CRP),fasting plasma glucose(FPG),fasting insulin(FINS)and FABP4 in the observation group were higher than those in the NDR group and the control group(P<0.05),and the serum NRG4 level was lower than those in the NDR group and the control group(P<0.05).The ser-um NRG4 level in the proliferative lesion group was lower than that in the non proliferative lesion group(P<0.05),and the FABP4 level was higher than that in the non proliferative lesion group(P<0.05).NRG4 was a protective factor for the occurrence of DR(P<0.05),while FABP4 was a risk factor for the occurrence of DR(P<0.05).The area under the curve(AUC)of serum NRG4 and FABP4 for diagnosing DR was 0.850 and 0.866,and the AUC of combined diagnosis was 0.930.The efficacy of the combination of the two was su-perior to that of the individual diagnosis of serum NRG4 and FABP4(Zcombination-NRG4=3.467,Zcombination-FABP4=2.987,P=0.001,0.002).Conclusion The serum FABP4 level in DR patients is greatly increased,while the NRG4 level is greatly decreased.The combination of the two has high diagnostic value for DR.

Objective To investigate the predictive value of combining polygenic risk score(PRS)with the National Institutes of Health Stroke Scale(NIHSS)socre for the development of deep venous thrombosis(DVT)in patients with ischemic stroke.Methods A total of 150 patients with ischemic stroke who were hos-pitalized in Jilin Provincial People's Hospital from December 2023 to May 2024 were selected as study sub-jects.After excluding patients who did not meet the criteria,139 patients were successfully followed up and di-vided into two groups based on whether DVT occurred.PRS strategy and fluorescence in situ hybridization(FISH)technology were used to detect the mutation of the gene loci associated with the risk of venous throm-boembolism(VTE).Based on these genotype data and the effect size of single nucleotide polymorphism(SNP)loci,the PRS score of patients was calculated through the model formula.The degree of neurological impairment was evaluated by NIHSS score.Receiver operating characteristics(ROC)curve was used to ana-lyze the efficacy of PRS score,NIHSS score and their combination in predicting ischemic stroke with lower limb DVT,and clinical data related to VTE formation were collected.Results There were no statistically sig-nificant differences between the two groups in terms of gender,age,body mass index(BMI),smoking,alcohol consumption,hypertension,diabetes,D-dimer(D-D),total cholesterol(TC),triglycerides(TG),and lipopro-tein(a)[(LP(a)]levels(P＞0.05).The PRS score,NIHSS score,and Barthel index in the DVT group were significantly higher than those in the non-DVT group,and the proportion of patients with bed rest exceeding 72 h and homocysteine(Hcy)levels were also relatively higher,with statistical significance(P＜0.05).Logis-tic regression analysis showed that PRS score＞2.55,NIHSS score ≥-3 and Barthel index＜60 were inde-pendent risk factors for lower limb DVT after ischemic stroke(P＜0.05).ROC curve analysis results showed that the area under the curve(AUC)of PRS score,NIHSS score and combined prediction of ischemic stroke combined with lower limb DVT were 0.655,0.747 and 0.763,respectively,and the AUC of combined predic-tion was higher than that of single prediction(P＜0.05).Conclusion PRS score combined with NIHSS score has good predictive efficacy for ischemic stroke complicated with DVT.

Objective:This paper is to propose a calibration model based on sine function which enables more choices to determine the functional relationship between the absorbance and the concentration of the tested substance.Methods:This paper uses Taylor series expansion and Levenberg-Marquardt to obtain the optimal parameters for the Sine model and then summarizes the characters of the Sine model. On the basis of these characters, this paper compares and evaluates the experimental data processed by the Sine model from four aspects: correctness, precision, linearity and correlation.Results:The generated sine function calibration model achieved deviations within ±3% of the national standard substance, precision ( CV%) less than 2%, and a linear correlation coefficient greater than 0.990 within the measurement range of 32-710 mg/L. The correlation coefficients between the sine model and other well-performing linear calibration models for 104 clinical samples were all greater than 0.990. Conclusions:The performance evaluation of the prealbumin assay kit using the sine function calibration model meets industry standards and shows good correlation with the results of clinical sample measurements. This indicates that the sine function calibration model can serve as a new calibration model for in vitro diagnostic research and clinical applications.

Hypoxemia is a common complication of pneumonia, asthma, and bronchopulmonary dysplasia in children.Rapid identification of hypoxemia is of great significance for the disposal and management of critical children.Pulse oximetry is recognized by the World Health Organization as the best way to monitor hypoxemia in children, and it can monitor pulse oxygen saturation noninvasively and continuously.Based on the related literature at home and abroad, combined with the clinical needs of pediatrics, the " Expert consensus on clinical application of pulse oximetry in children" is formulated to improve the understanding of pediatricians and nurses on the application in pediatric clinical practice, principle, operation techniques, and limitations of pulse oximetry.

Objective:To investigate the knowledge, attitudes, and practices (KAP) of pulse oximetry among pediatric healthcare providers in China and analyze the factor influencing the KAP.Methods:A self-developed questionnaire was used for an online research on the KAP of 11 849 pediatric healthcare providers from 31 provinces, autonomous regions, and municipalities of China from March 11 to 14, 2022.The factors influencing the KAP of pulse oximetry among pediatric healthcare providers were examined by Logistic regression. Results:The scores of KAP, of pulse oximetry were 5.57±0.96, 11.24±1.25 and 11.19±4.54, respectively.The corresponding scoring rates were 69.61%, 74.95%, and 55.99%, respectively. Logistic regression results showed that the gender and working years of pediatric healthcare providers, the region they were located, and whether their medical institution was equipped with pulse oximeters were the main factors affecting the knowledge score (all P<0.05). Main factors influencing the attitude score of pediatric healthcare providers included their knowledge score, gender, educational background, working years, region, medical institution level, and whether the medical institution was equipped with pulse oximeters (all P<0.05). For the practice score, the main influencing factors were the knowledge score, gender, age, and whether the medi-cal institution was equipped with pulse oximeters (all P<0.05). Conclusions:Chinese pediatric healthcare providers need to further improve their knowledge about and attitudes towards pulse oximetry.Pulse oximeters are evidently under-used.It is urgent to formulate policies or guidelines, strengthen education and training, improve knowledge and attitudes, equip more institutions with pulse oximeters, and popularize their application in medical institutions.

Objective:To investigate the etiology of necrotizing pneumonia (NP) in children and the clinical characteristics of NP caused by different pathogens in China.Methods:A retrospective, case-control study was performed in children with NP who were admitted to 13 hospitals in China from January 2008 to December 2019. The demographic and clinical information, laboratory data, etiological and radiological findings were analyzed. The data were divided into three groups based on the following years: 2008-2011, 2012-2015 and 2016-2019, and the distribution characteristics of the pathogens in different period were compared. Meanwhile, the pathogens of pediatric NP in the southern and northern China were compared. And the clinical characteristics of the Mycoplasma pneumoniae (MP) NP and the bacterial NP were also compared. T-test or Mann-Whitney nonparametric test was used for comparison of numerical variables, and χ 2 test was used for categorical variables. Results:A total of 494 children with NP were enrolled, the median ages were 4.7 (0.1-15.3) years, including 272 boys and 222 girls. Among these patients, pathogens were identified in 347 cases and the pathogen was unclear in the remaining 147 cases. The main pathogens were MP (238 cases), Streptococcus pneumoniae (SP) (61 cases), Staphylococcus aureus (SA) (51 cases), Pseudomonas aeruginosa (13 cases), Haemophilus influenzae (10 cases), adenovirus (10 cases), and influenza virus A (7 cases), respectively. MP was the most common pathogen in all three periods and the proportion increased yearly. The proportion of MP in 2016-2019 was significantly higher than that in 2012-2015 (52.1% (197/378) vs. 36.8% (32/87), χ 2= 6.654, P=0.010), while there was no significant difference in the proportion of MP in 2012-2015 and that in 2008-2011 (36.8% (32/87) vs. 31.0% (9/29), χ2=0.314, P=0.575).Regarding the regional distribution, 342 cases were in the southern China and 152 in the northern China. Also, MP was the most common pathogen in both regions, but the proportion of MP was higher and the proportion of SP was lower in the north than those in the south (60.5% (92/152) vs. 42.7% (146/342), χ 2=13.409, P<0.010; 7.9% (12/152) vs. 14.3% (49/342), χ 2= 4.023, P=0.045). Comparing the clinical characteristics of different pathogens, we found that fever and cough were the common symptoms in both single MP and single bacterial groups, but chest pain was more common (17.0% (34/200) vs. 6.1% (6/98), χ 2=6.697, P=0.010) while shortness of breath and wheezing were less common in MP group (16.0% (32/200) vs. 60.2% (59/98), χ 2=60.688, P<0.01; 4.5% (9/200) vs. 21.4% (21/98), χ 2=20.819, P<0.01, respectively). The white blood cell count, C-reactive protein and procalcitonin in the bacterial group were significantly higher than those in the MP group (14.7 (1.0-67.1)×10 9/L vs. 10.5 (2.5-32.2)×10 9/L, 122.5 (0.5-277.3) mg/L vs. 51.4 (0.5-200.0) g/L, 2.13 (0.05-100.00) μg/L vs. 0.24 (0.01-18.85) μg/L, Z=-3.719, -5.901 and -7.765, all P<0.01). Conclusions:The prevalence of pediatric NP in China shows an increasing trend during the past years. MP, SP and SA are the main pathogens of NP, and the most common clinical symptoms are fever and cough. The WBC count, C-reactive protein and procalcitonin in bacterial NP are significantly higher than those caused by MP.

Objective To evaluate the safety and efficacy of fenestrated endovascular aortic repair (fEVAR) using physician-modified stent grafts(PMSGs) to repair aortic dissection aneurysm.Methods Nine consecutive patients who underwent fEVAR using PMSGs from Jan 2018 to Jun 2018 were retrospectively reviewed.Results Nine PMSGs (6 Ankura stent grafts,3 COOK Zenith stent grafts) were deployed.Initial technical success rate was 97.0％ (32 of 33).Mean operative time was (303 ± 51) min.There were no in-hospital death and no perioperative neurology complications.All the patients survived at a median follow-up of 6.1 mouths (ranging 3-10 months).During follow up,no postoperative complications occurred,all target vessels remained patent and no fenestration-related type Ⅰ endoleak were observed.There are 3 cases of type Ⅱ and 2 cases of type Ⅲ endoleaks respectively.Conclusions FEVAR using PMSGs may be a viable alternative for patients with post aortic dissection aneurysm.

Objective To investigate the clinical features and outcomes of pulmonary surfactant protein C gene (SFTPC) 218 site mutation in children with pulmonary interstitial disease.Methods In this retrospective study,the clinical data,outcomes and influencing factors of 7 cases of SFTPC gene 218 site mutations in infants with interstitial lung disease in three hospitals from January 2013 to December 2016 were analyzed.Results Seven cases were full-term children,4 cases had the onset within 3 months after birth,2 cases after 1 year old,1 case within 3 months to 1 year,clinical manifestations of these cases were cough,shortness of breath,dyspnea,and limited growth and development,could not maintain life without additional oxygen supplementation,blood gas analysis showed hypoxemia,4 cases had clubbing.Chest CT showed diffuse ground glass-like change in both lungs.Three cases were positive for cytomegalovirus (CMV)-IgM or CMV-DNA.The mutations in 7 cases were exon 3,5 of which were SFTPC gene c.218T＞C,p.lle73Thr (heterozygous mutation),and 2 cases were SFTPC gene c.218T＞A,p.lle73Asn (homozygous mutation),1 case combined with ABCA3 gene mutations.Four patients were treated with prednisone alone,one with prednisone plus hydroxychloroquine,and two with symptomatic treatment.Three patients died,3 patients improved,and 1 patient was lost to follow-up.Conclusions The severity and prognosis of the children with SP-C 218 site mutation may be affected by many factors.Some children who received glucocorticoid alone do not have a good response.