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.

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 safety and effectiveness of robot-assisted total knee arthroplasty (TKA).Methods:From August 2021 to March 2022, the data of 69 patients who received robot-assisted TKA for inflammatory disease of knee in 6 hospitals were collected, including 24 males and 45 females, aged 52±6 years (range, 46-72 years), including 53 cases of knee osteoarthritis,10 cases of rheumatoid arthritis, and 6 cases of traumatic arthritis. Imaging data examination of patients was completed according to the multicenter specification. Preoperatively, the patient's CT data were extracted before surgery and a personalized prosthesis positioning plan was designed by the robotic system to determine the prosthesis size, lower limb force lines, and femoral and tibial osteotomy volumes; intraoperatively, the osteotomy template was robotically controlled to complete the osteotomy according to the prosthesis positioning plan, and the intraoperative osteotomy volumes were measured to verify the accuracy of the robot-assisted TKA osteotomy with the preoperative planning. Postoperatively, the lateral angle of the distal femur, the medial angle of the proximal tibia and the hip-knee-ankle angle were measured in the coronal plane according to radiographs; the postoperative outcome was evaluated 3 months after operation, using the American Knee Society score (KSS), including the KSS knee score and functional score.Results:The operative time was 97.3±2.3 min (range, 80-110 min) and the amount of bleeding was 320.0±6.2 ml (range, 300-350 ml) in 69 patients. Three months after operation, the mean range of motion of knee joint was increased from 82.2°±1.1° before surgery to 119.7°±0.8° after surgery ( t=27.65, P<0.001), and the line of force of lower limb was improved from 160.9°±0.5° before surgery to 178.0°±0.2° after surgery ( t=32.03, P<0.001). KSS-knee score increased from 54.8±0.7 points before operation to 85.0±0.5 points after operation, and KSS-functional score increased from 56.5±0.7 points before operation to 85.9±0.4 points after operation, the difference was statistically significant ( t=35.45, 36.58, P<0.001). The proportion of patients with intraoperative femoral and tibial osteotomies within 2 mm osteotomy error compared with preoperative planning was 97% for the lateral tibial plateau, 100% for the medial tibial plateau, 100% for the lateral distal femur, 99% for the medial distal femur, 93% for the lateral posterior femoral condyle, and 100% for the medial posterior femoral condyle; The proportion of patients with postoperative anteroposterior X-ray measurement angle error within 3° was: 100.0% for the distal lateral femoral angle, 100.0% for the proximal medial tibial angle, and 100% for the hip-knee-ankle angle. No complications occurred in all patients except for one case in which fat liquefaction occurred in the postoperative wound. Conclusion:Robot-assisted TKA is a safe and effective surgical method for the treatment of inflammatory disease of knee with accurate prosthesis installation and good postoperative recovery of lower limb alignment.

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.

ObjectiveTo predict the potential targets and possible related signaling pathways of Salviae Miltiorrhizae Radix et Rhizoma against bladder cancer （BC） based on network pharmacology and verify the potential molecular mechanism through in vitro cell experiment. MethodActive components of Salviae Miltiorrhizae Radix et Rhizoma were retrieved from Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform （TCMSP） and BC-related targets were searched from GeneCards and Online Mendelian Inheritance in Man （OMIM）. Via Venny2.1， the potential targets of Salviae Miltiorrhizae Radix et Rhizoma against BC were screened out and the Venn diagram was plotted. Protein-protein interaction （PPI） network was constructed by STRING， followed by Gene Ontology （GO） term enrichment and Kyoto Encyclopedia of Genes and Gnomes （KEGG） pathway enrichment with DAVID. Cell Counting Kit-8 （CCK-8） assay was employed to detect the inhibitory effect of tanshinone Ⅱ_A （Tan Ⅱ_A）， cryptotanshinone （CPT）， and luteolin （LUT） at different concentration （0， 1， 2， 4， 8， 16， 32 μmol·L^-1） on the proliferation of BC T24 and 5637 cells， propidium iodide （PI） staining to analyze the apoptosis of 5637 cells induced by Tan Ⅱ_A， CPT， and LUT （0， 4， 8 μmol·L^-1）， and Western blotting to detect the regulatory effect of Tan Ⅱ_A （0， 4， 8， 16 μmol·L^-1） on the expression of key target proteins. ResultA total of 65 active components and 39 anti-BC targets of Salviae Miltiorrhizae Radix et Rhizoma were screened out. The anti-BC targets were mainly involved in the KEGG pathways of neuron-ligand-receptor interaction， phosphatidylinositol 3-kinases （PI3K）/protein kinase B （Akt） signaling pathway， epidermal growth factor receptor （EGFR） tyrosine kinase inhibitor resistance， and hypoxia inducible factor （HIF）-1 signaling pathway. As for the CCK-8 assay， compared with the blank group， Tan Ⅱ_A， CPT， and LUT significantly inhibited the proliferation of T24 and 5637 cells， particularly the 5637 cells. The half maximal inhibitory concentration （IC₅₀） of Tan Ⅱ_A on 5637 cells was significantly lower than that of CPT and LUT. Moreover， compared with the blank group， Tan Ⅱ_A， CPT， and LUT all induced the apoptosis of 5637 cells， and the effect followed the order of Tan Ⅱ_A>CPT>LUT （P<0.05）. Western blot showed that Tan Ⅱ_A significantly reduced the expression of EGFR， p-PI3K， and p-Akt in 5637 cells in a concentration-dependent manner compared with the blank group （P<0.05）. ConclusionSalviae Miltiorrhizae Radix et Rhizoma exerts therapeutic effect on BC through multiple components， multiple targets， and multiple pathways. The mechanism is the likelihood that it down-regulates the expression of EGFR， p-PI3K， and p-Akt proteins， thus further inhibits cell proliferation， and induces apoptosis.

Objective:To explore the value of fusion imaging in the treatment of complex aortic pathology.Methods:A retrospective analysis was conducted of 29 patients with complex aortic pathology who underwent treatment with endovascular aortic repair using fusion imaging (FI+ ) technique or without FI (FI-) between June 2015 and June 2021. The perioperative outcomes and morbidity of the FI was assessed and the early results of follow up were evaluated.Results:The mean age of patients was (70.3±7.3) years old, and 24 (82.8%) males. Technical success was 96.5% (28/29). The FI+ group patients had lower procedure time[FI+ , (209±53) min vs. FI-, (306±24)min, P=0.005]and ionic contrast medium[(169±23)ml vs. (201±20)ml, P=0.040]. Contrast-induced acute kidney injury (CI-AKI)[3.4%(FI+ 0 vs. FI-6.7%, P=0.33)], and operation-related reintervention[6.9%(FI+ 0 vs. FI-13.3%, P=0.16)] were similar. There were no significant differences in blood loss, fluoroscopy time. Conclusion:FI technique improves the accuracy during positioning in complex endovascular aortic repair, could reduce aortic related reintervention rate, operation time and contrast dose. Further studies and development are needed to obtain optimal image quality and higher precision.

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.

Background and Objectives: To investigate the effect and the underlying mechanism of exosomes secreted by human umbilical cord mesenchymal stem cells (hUCMSCs) on diffuse alveolar hemorrhage (DAH) in murine lupus. Methods: and Results: Exosomes were extracted from cultured hUCMSCs by ultracentrifugation. The expressions of exosome markers (Alix, CD63 and TSG101) were measured for identification of hUCMSC-derived exosomes (hUCMSC-exosomes). The alveolar hemorrhage of DAH mice was revealed by H&E staining. The primary alveolar macrophages were isolated from bronchoalveolar lavage fluid (BALF) of DAH mice. The expressions of M1 macrophage markers (iNOS, IL-6, TNF-α and IL-1β ) and M2 macrophage markers (Arg1, IL-10, TGF-β and chi3l3) were detected. Flow cytometry measured the ratio of M1/M2 macrophages. ELISA measured the secretion of pro-inflammatory cytokines (IL-6 and TNF-α) and anti-inflammatory cytokines (IL-10 and TGF-β ). DAH mice had hemorrhage and small-vessel vasculitis in the lung, with neutrophil and monocyte infiltration observed around the capillary and small artery. Furthermore, increases of IL-6 and TNF-α, and decreases of IL-10 and TGF-β were detected in the BALF of DAH mice. M1 makers were overexpressed in alveolar macrophages of DAH mice while M2 makers were lowly expressed. DAH mice had a higher proportion of M1 macrophages than M2 macrophages. After hUCMSC-exosome or methylprednisolone treatment in DAH mice, the alveolar injuries and inflammatory responses were attenuated, and the proportion of M2 macrophages was increased. Conclusions hUCMSC-exosomes attenuate DAH-induced inflammatory responses and alveolar hemorrhage by regulating macrophage polarization.

Background and Objectives: To investigate the effect and the underlying mechanism of exosomes secreted by human umbilical cord mesenchymal stem cells (hUCMSCs) on diffuse alveolar hemorrhage (DAH) in murine lupus. Methods: and Results: Exosomes were extracted from cultured hUCMSCs by ultracentrifugation. The expressions of exosome markers (Alix, CD63 and TSG101) were measured for identification of hUCMSC-derived exosomes (hUCMSC-exosomes). The alveolar hemorrhage of DAH mice was revealed by H&E staining. The primary alveolar macrophages were isolated from bronchoalveolar lavage fluid (BALF) of DAH mice. The expressions of M1 macrophage markers (iNOS, IL-6, TNF-α and IL-1β ) and M2 macrophage markers (Arg1, IL-10, TGF-β and chi3l3) were detected. Flow cytometry measured the ratio of M1/M2 macrophages. ELISA measured the secretion of pro-inflammatory cytokines (IL-6 and TNF-α) and anti-inflammatory cytokines (IL-10 and TGF-β ). DAH mice had hemorrhage and small-vessel vasculitis in the lung, with neutrophil and monocyte infiltration observed around the capillary and small artery. Furthermore, increases of IL-6 and TNF-α, and decreases of IL-10 and TGF-β were detected in the BALF of DAH mice. M1 makers were overexpressed in alveolar macrophages of DAH mice while M2 makers were lowly expressed. DAH mice had a higher proportion of M1 macrophages than M2 macrophages. After hUCMSC-exosome or methylprednisolone treatment in DAH mice, the alveolar injuries and inflammatory responses were attenuated, and the proportion of M2 macrophages was increased. Conclusions hUCMSC-exosomes attenuate DAH-induced inflammatory responses and alveolar hemorrhage by regulating macrophage polarization.