ObjectiveTo study the chemical constituents of Painong powder and the constituents absorbed into blood after oral administration to rats by ultra performance liquid chromatography-quadrupole-electrostatic field orbitrap high-resolution mass spectrometry （UPLC-Q-Orbitrap-MS）. MethodsUPLC-Q-Orbitrap-MS was employed for mass spectrometry data acquisition. The chemical constituents of Painong Powder and the constituents absorbed into blood were characterized and identified via Xcalibur 4.2 and Compound Discoverer v3.3.1 （CD） based on retention time， accurate molecular weights， secondary fragmentation ions， and comparison with reference standards and literature reports. ResultsA total of 176 chemical compounds， including 56 flavonoids， 42 triterpenoid saponins， 23 monoterpenes， 7 coumarins， 5 tannins， and other 43 compounds were identified from Painong powder. 49 components were identified in the rat plasma after oral administration of Painong powder， including 33 prototype constituents and 16 metabolites. The major metabolic pathways included hydrolysis in phase Ⅰ metabolic reactions， as well as methylation， sulfation， and glucuronidation in phase Ⅱ metabolic reaction. ConclusionThe method comprehensively identified the chemical constituents of Painong powder both in vitro and in vivo， and may provide a reference for the study of quality control and clinical applications.

Diabetic nephropathy （DKD）， as a common microvascular complication of diabetes mellitus （DM）， is a major cause of end-stage renal disease （ESRD）. Its clinical manifestations include increased urinary protein excretion， thickening of the glomerular basement membrane， and renal tubulointerstitial fibrosis. The pathogenesis of DKD is complex and involves multiple factors， including disordered glucose metabolism， hemodynamic alterations， and oxidative stress. Although modern medical approaches can alleviate certain symptoms， they still have limitations such as insufficient therapeutic targeting and prominent adverse effects. The transforming growth factor-β/Smad （TGF-β/Smad） signaling pathway is not only a tissue fibrosis pathway that has attracted considerable attention in recent years， but also regulates multiple protein molecules， including the glomerular podocyte slit diaphragm protein Podocin， interleukin-1β （IL-1β）， and superoxide dismutase （SOD）， thereby participating in various pathological processes and ultimately mediating renal injury. Flavonoid compounds， owing to their sustained pharmacological effects， broad spectrum of action， and high safety profile， have become ideal candidates for targeted therapy research in DKD. Existing studies have shown that these compounds can exert inhibitory effects on renal fibrosis， alleviate inflammatory responses， protect podocytes， and reduce oxidative stress by regulating the interactions between the TGF-β/Smad signaling pathway and the aforementioned protein molecules， thereby maintaining renal structure and function， reducing proteinuria， and significantly improving DKD lesions. This review briefly outlines the composition and functions of the TGF-β/Smad signaling pathway， elucidates the mechanisms by which this pathway regulates DKD， and focuses on summarizing major studies from the past decade on flavonoid-based interventions in DKD through targeted inhibition of the TGF-β/Smad signaling pathway. Furthermore， it discusses the considerable therapeutic potential of flavonoids in the treatment of this disease， aiming to provide a scientific basis for future clinical prevention and treatment of DKD and to promote the development of targeted drugs.

The pain-evoked potential electroencephalogram (EEG) is an effective electrophysiological indicator for pain assessment, yet its extraction is challenging due to interference from background activity and involuntary blinks. Although existing blink artifact-removal methods show efficacy, they face limitations such as the need for reference signals, neglect of individual differences, and reliance on user input, hindering their practical application in clinical pain assessments. In this paper, we propose a novel framework applying adaptive quadrature mirror filter banks (AQMFB) with discrete wavelet transform (DWT) to remove blink artifacts in pain EEG. Unlike traditional DWT methods that apply fixed wavelets across subjects, our method adapts wavelet construction based on the characteristics of EEG. Experimental results demonstrate that AQMFB-DWT outperforms four leading methods in removing blink artifacts with minimal distortion of pain information, all within an acceptable processing time. This technique is a valuable preprocessing step for enhancing the extraction of pain-evoked potentials.
Humans ; Artifacts ; Blinking/physiology* ; Electroencephalography/methods* ; Pain/diagnosis* ; Male ; Wavelet Analysis ; Adult ; Female ; Evoked Potentials/physiology* ; Young Adult ; Brain/physiopathology* ; Pain Measurement/methods* ; Signal Processing, Computer-Assisted

Objective:To study the regulatory effect of Wumen-Yiji powder on 5-hydroxytryptamine (5-HT) signal transduction system in intestine and hypothalamus of diarrhea irritable bowel syndrome (IBS-D) model rats. Methods:Sixty male SD rats were randomly divided into blank group (10 rats) and diarrhea irritable bowel syndrome group (50 rats). The diarrhea irritable bowel syndrome group formed the diarrhea irritable bowel syndrome model after 2 weeks of senna leaf gavage and restraint stress. They were randomly divided into model group, deshute group (1.5 mg/kg), low, medium and high dose group of Wumen-Yiji San (6, 12, 24 g/kg), with 10 rats in each group. After continuous administration for 2 weeks, the contents of 5-HT in serum, colon and hypothalamus were detected by ELISA; HE staining was used to observe the pathological changes of colon in each group. The protein and mRNA levels of tryptophan hydroxylase 1 (TPH-1), serotonin receptor 3 (5-HT3R), serotonin receptor 4 (5-HT4R), serotonin transporter (SERT) in colon and hypothalamus were detected by Western blot and RT-PCR, respectively. Results:Compared with the model group, the pathological morphology of colon in each treatment group was improved. Compared with the model group, the level of 5-HT in serum and colon significantly decreased ( P<0.05), and the level of 5-HT in hypothalamus of rats in the low, medium, high dose group of Wumen-Yiji San significantly increased ( P<0.05). The expression of TPH-1, 5-HT3R and 5-HT4R protein significantly decreased ( P<0.05), and the expression of SERT protein in the medium, high dose group of Wumen-Yiji San significantly increased ( P<0.05). The expression of TPH-1, 5-HT3R and 5-HT4R protein in hypothalamus increased ( P<0.05), and the expression of SERT protein in the high dose group of Wumen-Yiji San significantly decreased ( P<0.05). The mRNA levels of TPH-1 (4.778 ± 0.604, 3.278 ± 0.668, 1.670 ± 0.361 vs. 6.877 ± 0.148), 5-HT3R (3.807 ± 0.463, 2.697 ± 0.455, 1.132 ± 0.136 vs. 6.322 ± 0.778), 5-HT4R (4.521 ± 0.234, 2.801 ± 0.351, 1.331 ± 0.142 vs. 6.741 ± 0.293) in colon tissue of low, medium and high dose groups of Wumen-Yiji San decreased ( P<0.05). The level of 5-HT4R mRNA (0.616 ± 0.208, 0.726 ± 0.226 vs. 0.521 ± 0.062) increased ( P<0.05), and the level of SERT mRNA (1.563 ± 1.023 vs. 2.612 ± 1.035) in medium, high dose group of Wumen-Yiji San decreased ( P<0.05). Conclusion:The result showed that Wumen-Yiji San could regulate the expression of 5-HT signaling system relating proteins and mRNA in the colon and hypothalamus of IBS-D rats within a certain dose range, so as to improve the symptoms of IBS-D.

Objective:To investigate the effects of miRNA-499a-5p targeting CD38 on cardiomyocyte injury induced by hydrogen peroxide (H 2O 2) and the possible mechanism. Methods:H9c2 cardiomyocytes were cultured in vitro and induced with H 2O 2 to establish the cardiomyocyte injury model. Four groups including control, H 2O 2, H 2O 2+ negative control (NC) and H 2O 2+ miRNA-499a-5p groups were set up. Real-time quantitative PCR (RT-qPCR) and Western blot were used to detect the expression of miRNA-499a-5p and CD38 in cardiomyocytes, respectively. MTT assay was used to measure the survival rates of cardiomyocytes. The levels of reactive oxygen species (ROS) and the activity of lactate dehydrogenase (LDH) were analyzed with test kits. Annexin V-FITC/PI double staining method was used to detect the apoptosis rates of cardiomyocytes. Western blot was used to detect the expression of B-cell lymphoma/leukemia-2 (Bcl-2), Bcl-2-related X protein (Bax), phosphoinositide 3-kinase (PI3K), phosphorylated PI3K (p-PI3K), protein kinase B (Akt) and phosphorylated Akt (p-Akt). Dual luciferase reporter assay was used to detect the targeting relationship between miRNA-499a-5p and CD38. Results:Compared with the control group, the expression of miRNA-499a-5p, Bcl-2, p-PI3K and p-Akt and the survival rate of cardiomyocytes were significantly reduced in the H 2O 2 group ( P<0.05), while the expression of CD38 and Bax, ROS level, LDH activity and the apoptosis rate were significantly increased ( P<0.05). Compared with the H 2O 2 group, the expression of miRNA-499a-5p, Bcl-2, p-PI3K and p-Akt and the survival rate of cardiomyocytes were significantly increased in the H 2O 2+ miRNA-499a-5p group ( P<0.05), while the expression of CD38 and Bax, ROS level, LDH activity and the apoptosis rate were significantly decreased ( P<0.05). Dual luciferase reporter assay confirmed that CD38 was a target gene of miRNA-499a-5p. Conclusions:miRNA-499a-5p could alleviate H 2O 2-induced cardiomyocyte injury by inhibiting the expression of CD38 and the PI3K/Akt signaling pathway might be involved.

Objective:To investigate the cognition and willingness of nursing staff to Internet plus nursing service, and analyze the related factors that affect their participation in Internet plus nursing service.Methods:From April to May 2019, 150 nurses from three hospitals in Weifang were investigated by questionnaire and key person interview. Descriptive analysis and binary logistic regression analysis were used to analyze the intention of nursing staff to participate in Internet plus nursing service. The interview mode was used to analyze the appropriate mode of Internet plus nursing service from the perspective of nursing staff.Results:142 valid questionnaires were obtained, of which 137(96.5%)indicated willingness to provide Internet plus nursing services, and 135(95.1%) realized the necessity of the service. Education, marriage, nurses′judgment on the necessity of the service and their own subjective judgment of their competence were the factors affecting nurses′ participation in the Internet plus nursing service.Conclusions:Multiple factors affect the choice of nursing staff′s behavior in Internet plus nursing service.From the perspective of nursing staff, the Internet plus nursing service mode needs joint efforts from many aspects.

Objective: To explore the correlation between sleep and laryngopharyngeal reflux disease by epidemiological approaches. Methods: From May 1, 2017 to April 30, 2018, data of age, gender, height, weight, smoking, alcohol consumption, constipation and high fat diet in patients in Otorhinolaryngology specialist clinic, the Eighth Medical Center, General Hospital of the Chinese PLA were retrospectively analyzed. Reflux Symptom Index (RSI), Pittsburgh Sleep Quality Index (PSQI) and Hospital Anxiety and Depression Scale (HADS)were filled. According to RSI scores, patients were divided into case group and control group. The differences of the above indicators between the two groups were compared by Stata 12.0 software, and the risk factors of LPRD were analyzed by multivariate Logistic regression. Results: A total of 908 patients were enrolled, including 166 in the case group and 742 in the control group. There was no significant difference in BMI, smoking, drinking, constipation and high fat diet between the two groups (all P>0.05). The PSQI, anxiety and depression score of the case group were higher than those of the control group. The anxiety and depression scores of the patients with sleep disorders in the case group were significantly higher than those of the normal sleepers (all P<0.05). RSI of the patients with sleep disorders was higher than that of the patients with normal sleep(9.5[4.0,16.0]vs. 5.0[1.0,10.0], Z=-6.07, P<0.001). Multivariate analysis showed that sleep disorder was the risk factors of LPRD (OR=2.59, 95%CI 1.75-3.84). Conclusions Sleep disorder is related to the occurrence of LPRD. The association between LPRD and sleep disturbances is bidirectional. Sleep disorder may also be related to the anxiety and depression in LPRD patients. Handling sleep disorder timely may benefit LPRD patients.

The policy model of G. C. Edwards was used to study the policies on building a countywide medical community ( CMC), and identify problems in such aspects as policy communication, resources, disposition and bureaucratic structure. The analysis found that enriching health resources at primary level and powerful government support are creating ideal environment for the construction of CMC. But due to its preliminary development, rooms of improvement of its policy design, and unclear enforcement standards, there appear behavioral polarizations at local health authorities. For example, some are proactive to explore and accumulate rich experiences, while the most take a wait and see stand, or even take administrative means to cope with their authorities by forming medical communities in form only. A small part of county hospitals, thanks to support from the government and inherent conditions, take active measures in this direction as policy frontrunners. On the other hand, most county hospitals prefer to be policy followers in order to avoid cost and risks of the reform. In the worst cases, a few county hospitals have become free riders of the policy, and attempt to take advantages of their primary health institutions. Primary health institutions warmly embrace CMC, but their limited service capability constitutes roadblocks in CMC construction. What is more, poor communication and collaboration mechanisms among systems and authorities hinder the effective policy synergy and health service integration of CMS.

Objective To analyze the motives and tactics of township health centers ( THC) to participate in the countywide medical communities of Shandong province. Methods Such tools as the new institutionalism, rational choice and social network theories, as well as the constituent ratios and Pearson correlation coefficient of data were used in a survey in August 2018 with managers of 264 THCs in Shandong. It aimed to learn from the respondents their motives, tactics, and behaviors to participate in such communities. Results Theoretical analysis of the results found that their participation was bound by both institutional environment and technical environment. For example, compliance tactics, accompanied by efficiency, was adopted to cope with stress from institutional environment. Exploratory tactics, accompanied by legitimacy, was adopted to cope with stress from technical environment. The figures showed 87. 5％ of 264 THCs investigated participated in such communities, and their main motives were in turn to follow government requests (86. 1％ ) and to seek development opportunities (69. 7％ ). The critical criteria of partner selection were in turn technological level (83. 5％ ) and matching of resources (77. 9％ ). Of 231 THCs which participated in the communities, 95. 2％ joined in countywide medical communities, and 28. 6％ participated in other forms of medical alliances. Conclusions THCs showed high organizational convergence in their participation, and adopted diversified strategies of participation in medical alliance.

Objective To investigate the effect of Early Intervention Denver Model ( Early Start Denver Model,ESDM) on children with autism spectrum disorder( ASD). Methods From May 2017 to April 2018,forty four children aged 2-5 years with ASD were enrolled in the study and were randomly divided into the experimental group(n=20) and the control group (n=20). The experimental group received ESDM rehabilitation intervention and the control group received conventional rehabilitation intervention. Before and 6 months after intervention,all children were assessed by the Psycho-educational Profile-3rd Edition ( PEP-3). Results After 6 months of intervention,the developmental age of cognition (30 (26,34),33(30,44);Z=-3. 728,P<0. 001),imitation (33(29,40),38( 32,43); Z=-2. 010,P=0. 044),expression language (29(23,39),41( 33,50); Z=-3. 923, P<0. 01), receptive language ( 25 ( 20,32),34 ( 28,38); Z=-3. 727,P<0. 01) and fine motor (29(23,41),39(33,47) ;Z=-2. 704,P=0. 007) of the control group were significantly higher than those before intervention. In the experimental group,the developmental age of cognition (25 ( 21,32),37 ( 32,40); Z=-3. 922, P<0. 01),imitation ( 22 ( 17,35),39 ( 38,42); Z= -3. 826,P<0. 01),expression language (30(24,35),47( 37,53); Z=-3. 824,P<0. 01),receptive lan-guage (22(15,32),37(30,43); Z=-3. 924,P<0. 01),fine motor (25(22,33),43(30,52); Z=-3. 924, P<0. 01) and gross motor ( 24(17,38),40(27,43); Z=-3. 523,P<0. 01) were significantly higher than those before intervention. Compared with the control group,the experimental group had significantly greater changes in the five regions:cognition(6(3,10),11(10,20); Z=-2. 821,P=0. 005),expression language (6(4,9),12(7,18); Z=-3. 278,P=0. 001),receptive language(5(3,10),12(7,18); Z=-3. 299,P=0. 001),fine motor (7(1,10),13(10,22); Z=-3. 038,P=0. 002)and gross motor(1(0,10),11(5,16);Z=-2. 568,P=0. 01) of PEP-3 after intervention. Conclusion Both conventional intervention and ESDM intervention can improve the cognitive,expression language,receptive language,imitation and fine motor abili-ty of children with ASD aged from 2 to 5 years,but ESDM intervention is more effective on improving the cog-nitive,language,imitation and fine motor ability of children with ASD.