OBJECTIVE To establish the UPLC fingerprint and the method for multi-component content determination in Jingangteng capsules， and to evaluate its quality by combining chemical pattern recognition analysis. METHODS An UPLC method was established. Separation was performed on a Zorbax SB-C 18 Rapid Resolution HD column， with acetonitrile-0.1% formic acid as the mobile phase for gradient elution.Using the Similarity Evaluation System for Chromatographic Fingerprints of Traditional Chinese Medicines （2012 edition）， UPLC fi ngerprints were established for 10 batches of Jingangteng capsules， and similarity was evaluated. SPSS 22.0 and SIMCA 14.1 software were used to perform hierarchial-cluster analysis and orthogonal partial least squares discriminant analysis （OPLS-DA）， respectively. The same UPLC method was employed to determine the contents of chlorogenic acid， 3，5-dihydroxy-2-methylbenzoic acid-3- O -glucoside （M1）， caffeic acid， astilbin， oxyresveratrol， quercitrin and resveratrol in the 10 batches of samples. RESULTS A total of 17 common peaks were identified in UPLC fingerprints of the 10 batches of samples， of which 7 were identified as chlorogenic acid， M1， caffeic acid， astilbin， oxyresveratrol， quercitrin， and resveratrol. The similarities of 10 batches of samples ranged from 0.820 to 0.985. The results of hierarchial-cluster analysis showed that 10 batches of samples were grouped into four categories： S1-S4 formed one group， S5 and S6 formed another， S7， S8 and S10 formed a third， and S9 formed a fourth， consistent with the OPLS-DA results； the variable importance projection values for peaks 7， 10， 2， 16 （resveratrol）， 13 （oxyresveratrol）， 11， 6 （caffeic acid）， 5 （M1） and 15 （quercitrin） were ＞1. Quantitative analysis results showed that the contents of chlorogenic acid， M1， caffeic acid， astilbin， oxyresveratrol， quercitrin， and resveratrol were 1.650 8-4.213 7， 0.636 2-2.161 7， 0.031 0-0.086 5， 0.239 1-1.069 3， 0.211 9-1.104 0， 0.488 8-2.399 2， and 0.164 0-0.699 8 mg/g， respectively. CONCLUSIONS UPLC fingerprint and content determination methods established in this study are simple to operate， accurate， reliable and reproducible； when combined with chemical pattern recognition analysis， they can be used to evaluate the quality of Jingangteng capsules. Nine components， such as resveratrol， oxyresveratrol， caffeic acid， M1 and quercitrin， may serve as markers of quality variation.

OBJECTIVES: To investigate the neuroprotective effects of electroacupuncture (EA) preconditioning against cerebral ischemia-reperfusion injury (CIRI) mediated by gut microbiota modulation, Nrf2/HO-1 pathway activation, and ferroptosis suppression. METHODS: Adult male SD rats were divided into sham operation group, CIRI model group, and EA preconditioning group. In the latter two groups, rat models of CIRI were established by middle cerebral artery occlusion (MCAO), and in EA preconditioning group, EA was applied at Baihui (DU20) and Zusanli (ST36) for 3 days before modeling. Neurological deficits, cerebral infarction, and hippocampal pathology of the rats were evaluated using behavioral tests, TTC staining, and Nissl and HE staining, and the oxidative stress markers (MDA, ROS, and SOD), apoptosis/ferroptosis-related proteins (Bax, Bcl-2, GPX4, and SLC7A11), and changes in gut microbiota were analyzed. RESULTS: EA preconditioning significantly reduced neurological deficits, decreased infarct volume, promoted hippocampal neuronal survival, and improved structural integrity of the hippocampal neurons in MCAO rats. EA preconditioning also significantly lowered MDA and ROS and increased SOD levels, upregulated Bcl-2, GPX4, and SLC7A11 expressions, and downregulated Bax expression in the hippocampal tissue of the rats, causing also activation of Nrf2/HO-1 signaling and improvement of gut microbiota composition. CONCLUSIONS EA preconditioning alleviates CIRI in rats by suppressing ferroptosis and apoptosis, enhancing antioxidant defenses via activating Nrf2/HO-1 signaling, and regulating the gut-brain axis.
Animals ; Electroacupuncture ; NF-E2-Related Factor 2/metabolism* ; Rats, Sprague-Dawley ; Signal Transduction ; Reperfusion Injury/therapy* ; Ferroptosis ; Male ; Rats ; Brain Ischemia ; Gastrointestinal Microbiome ; Heme Oxygenase (Decyclizing)/metabolism* ; Brain/metabolism* ; Oxidative Stress ; Heme Oxygenase-1/metabolism* ; Apoptosis

ObjectiveTo investigate the protective effect and mechanism of action of flavonoid combination of Alpiniae Officinarum Rhizoma （A. officinarum） against Helicobacter pylori （H. pylori） gastritis in mice. MethodsAfter acclimatization for one week， 56 SPF-grade healthy C57BL/6J mice were gavaged with mixed antibiotics for three consecutive days. They were randomly divided into a normal group， model group， positive drug group （triple therapy group）， and low- and high-dose groups （100， 200 mg·kg^-1） of flavonoid combination of A. officinarum. The H. pylori gastritis mice model was established by gavage with H. pylori bacterial suspension in each group except for the normal group. After successful modeling， mice were administrated with corresponding drugs once a day for two weeks. Hematoxylin-eosin （HE） staining was used to observe the pathological changes in gastric tissue. Rapid urease test paper was used to detect the positive rate of H. pylori. Silver staining was used to observe the H. pylori adherence on the surface of gastric tissue. Immunohistochemistry was used to detect the protein expression of interleukin-8 （IL）-8 and myeloid differentiation factor （MyD88） in gastric tissue. The serum levels of IL-6， tumor necrosis factor-α （TNF-α）， IL-8， and IL-1β were detected by enzyme-linked immunosorbent assay （ELISA）. The expressions of phosphatidylinositol 3-kinase/protein kinase B （PI3K/Akt） protein were detected by Western blot. ResultsCompared with those in the normal group， mice in the model group had lower gastric weight coefficients， higher pH of gastric juice， 100% H. pylori infection rate， and significantly changed gastric histopathology. The expressions of IL-8 and MyD88 proteins in the gastric tissue of mice in the model group were significantly elevated， and the serum levels of inflammatory factors IL-6， TNF-α， IL-8， and IL-1β were significantly up-regulated in mice. Compared with that in the model group， the gastric weight coefficient of mice in each treatment group of the flavonoid combinations of A. officinarum was elevated （P<0.01）， and the pH of gastric juice was reduced （P<0.01）. The infection rate of H. pylori was reduced. The expressions of IL-8 and MyD88 proteins in the gastric tissue of mice in the treatment groups were significantly reduced （P<0.01）， and the serum levels of inflammatory factors IL-6， TNF-α， IL-8， and IL-1β were significantly reduced in a dose-dependent manner （P<0.01）. The flavonoid combinations of A. officinarum down-regulated the expression of PI3K and Akt proteins in H. pylori gastritis-infected cells （P<0.01）. ConclusionThe protective effect of flavonoid combinations of A. officinarum against H. pylori gastritis is associated with the inhibition of H. pylori infection rate and regulation of PI3K/Akt signaling pathway， resulting in inhibiting the release of inflammatory factors.

Objective:To explore the correlation between abnormal vital signs (e.g., heart rate, oxygen saturation, and body temperature) and acute exacerbations in patients with chronic obstructive pulmonary disease (COPD), as well as to evaluate the clinical value of continuous monitoring via wearable devices for the early warning and intervention.Methods:A multicenter cross-sectional study enrolled 335 patients with stable chronic obstructive pulmonary disease (COPD) from 12 community health centers in Beijing and Chengdu between June 2023 and May 2024. General demographic and clinical data were collected, and each participant underwent continuous monitoring of resting heart rate, oxygen saturation, and body temperature using wearable devices for 21 days. Based on whether participants had experienced acute exacerbations requiring outpatient, emergency, or inpatient treatment within the previous year, they were categorized into the acute exacerbation group and the non-exacerbation group. Differences in physiological parameters between the acute exacerbation group and non-exacerbation group were analyzed, and contributing factors were assessed using logistic regression analysis.Results:A total of 335 patients with stable COPD were enrolled, including 252 cases (75.22%) in the acute exacerbation group and 83 cases (24.78%) in the non-acute exacerbation group. There were no statistically significant differences in age, sex distribution, comorbidities, or baseline lung function between the two groups (all P>0.05). Compared with the non-acute exacerbation group, patients in the acute exacerbation group had a faster resting heart rate((76.01 ± 7.78) beats/min vs. (72.72 ± 7.35) beats/min, t=3.126, P=0.002), a higher proportion of patients with decreased oxygen saturation (1.75% (0.97%, 3.03%) vs. 0.86% (0.44%, 1.65%), Z=11.086, P=0.001), and a higher proportion of patients with elevated body temperature (0.60% (0.39%, 1.03%) vs. 0.31% (0.17%, 0.54%), Z=7.314, P=0.007). Logistic regression analysis showed that advanced age ( OR=1.051, 95% CI: 1.023-1.080), increased heart rate ( OR=1.055, 95% CI:1.013-1.098), decreased oxygen saturation ( OR=1.197, 95% CI:1.023-1.400), and elevated body temperature ( OR=1.777, 95% CI:1.148-2.752) were positively associated factors for acute exacerbation of COPD. Conclusions:Abnormalities in physiological indicators such as heart rate, oxygen saturation, and body temperature are associated with acute exacerbations in COPD patients. Continuous monitoring using wearable devices may provide a new method for early warning and timely intervention in COPD exacerbations.

Objective:To explore the correlation between abnormal vital signs (e.g., heart rate, oxygen saturation, and body temperature) and acute exacerbations in patients with chronic obstructive pulmonary disease (COPD), as well as to evaluate the clinical value of continuous monitoring via wearable devices for the early warning and intervention.Methods:A multicenter cross-sectional study enrolled 335 patients with stable chronic obstructive pulmonary disease (COPD) from 12 community health centers in Beijing and Chengdu between June 2023 and May 2024. General demographic and clinical data were collected, and each participant underwent continuous monitoring of resting heart rate, oxygen saturation, and body temperature using wearable devices for 21 days. Based on whether participants had experienced acute exacerbations requiring outpatient, emergency, or inpatient treatment within the previous year, they were categorized into the acute exacerbation group and the non-exacerbation group. Differences in physiological parameters between the acute exacerbation group and non-exacerbation group were analyzed, and contributing factors were assessed using logistic regression analysis.Results:A total of 335 patients with stable COPD were enrolled, including 252 cases (75.22%) in the acute exacerbation group and 83 cases (24.78%) in the non-acute exacerbation group. There were no statistically significant differences in age, sex distribution, comorbidities, or baseline lung function between the two groups (all P>0.05). Compared with the non-acute exacerbation group, patients in the acute exacerbation group had a faster resting heart rate((76.01 ± 7.78) beats/min vs. (72.72 ± 7.35) beats/min, t=3.126, P=0.002), a higher proportion of patients with decreased oxygen saturation (1.75% (0.97%, 3.03%) vs. 0.86% (0.44%, 1.65%), Z=11.086, P=0.001), and a higher proportion of patients with elevated body temperature (0.60% (0.39%, 1.03%) vs. 0.31% (0.17%, 0.54%), Z=7.314, P=0.007). Logistic regression analysis showed that advanced age ( OR=1.051, 95% CI: 1.023-1.080), increased heart rate ( OR=1.055, 95% CI:1.013-1.098), decreased oxygen saturation ( OR=1.197, 95% CI:1.023-1.400), and elevated body temperature ( OR=1.777, 95% CI:1.148-2.752) were positively associated factors for acute exacerbation of COPD. Conclusions:Abnormalities in physiological indicators such as heart rate, oxygen saturation, and body temperature are associated with acute exacerbations in COPD patients. Continuous monitoring using wearable devices may provide a new method for early warning and timely intervention in COPD exacerbations.

Objective To explore the biological basis of different diseases with the same syndrome for pulmonary related comorbidities(pulmonary hypertension,obstructive sleep apnea syndrome,chronic obstructive pulmonary disease,lung cancer)in idiopathic pulmonary fibrosis(IPF)through genomic bioinformatics analysis.Methods GSE110147,GSE113439,GSE135917,GSE106986 and GSE118370 datasets were downloaded as research subjects.The differential genes between each disease group and the control group were screened.Cytoscape 3.10.0 software was used for topology analysis to screen core genes.OmicShare was used to perform GO and KEGG pathway enrichment analyses on core genes.Results A total of 23 core genes related to IPF was obtained.GO enrichment analysis showed that core genes were mainly enriched in biological processes such as cellular process,metabolic process,biological regulation/biological process,developmental process,localization,response to stimulus,immune system process and signaling;in cellular components such as cellular anatomical entity and protein-containing complex;in molecular functions such as binding,catalytic activity,structural molecule activity,molecular adaptor activity,molecular function regulator and transcription regulator activity.KEGG pathway enrichment analysis showed that core genes were mainly enriched in ribosome biogenesis in eukaryotes,AGE-RAGE signaling pathway in diabetic complications,Th17 cell differentiation,JAK-STAT signaling pathway,RNA polymerase,neutrophil extracellular trap formation.Conclusion Using genomic bioinformatics analysis to explore the core genes and signaling pathways of pulmonary related comorbidities in IPF can reveal the mechanism of different diseases with the same syndrome for pulmonary related comorbidities in IPF to a certain extent.

Objective:To investigate the effects of 3 adhesives on the bond force and durability of polished and glazed zirconia ceram-ics to orthodontic metal brackets respectively.Methods:Universal adhesives,Single Bond Universal(SBU)and Prime&Bond Universal(PBU)were respectively used to bond polished and glazed zirconia to metal braces of maxillary central incisors using TransbondTM MIP(TM)as the control.The shear bond strength(SBS),the fracture morphology and adhesive residual index(ARI)were examed after wa-ter bath or water bath-thermal cycling storage.Results:The adhesive(P＜0.001)and storage conditions(P＜0.001)significantly af-fected the shear bond strength of zirconia to brackets.There was no significant difference between the polished or glazed groups(P=0.09).SBU showed the stronger SBS and lower ABI,there were significant differences in ARI scores among the 3 cements(P＜0.001).Conclusion:SBU may have better bonding performance than PBU and TM in the orthodontic bonding of polished or glazed zir-conia surfaces to the zirconia ceramics.

Objective:To investigate the risk factors for 1-year survival rate in patients with spinal metastasis secondary to lung cancer.Methods:The data of 343 patients with spinal metastases secondary to lung cancer from January 2011 to December 2018 were retrospectively studied. There were 188 males (54.8%) and 155 females (45.2%) with an average age of 59.47±10.21 years old (range 23-91 years). The patients were divided into operation group (150 cases, 43.7%) and non operation group (193 cases, 56.3%). The demographics, types of primary tumor, non spinal metastasis, visceral metastasis, spinal metastasis and segments, pathological fractures of vertebra, Frankel classification, physical function status (Karnofsky performance scale, KPS), visual analogue score (VAS), the spinal instability neoplastic score (SINS) were recorded and analyzed. The impact of different treatments on the survival prognosis of patients with spinal metastasis was evaluated. The independent factors affecting survival in those patients were analyzed by Cox proportional hazards regression model.Results:The peak incidence of spinal metastases was found in the age group of 46-60 years (43.7%, 150/343). 38.5% (132/343) of the patients had pathological fractures of the involved vertebral body. 58.3% (200/343) of the patients had extraspinal bone metastasis. 36.2% (124/343) of the patients had visceral metastasis. Among the primary tumors, adenocarcinoma was the most common tpye (61.5%, 211/343), followed by large cell lung cancer (12.5%, 43/343), small cell lung cancer (6.4%, 22/343), squamous cell cancer (6.1%, 21/343) and mixed cell lung cancer (5.3%, 18/343). The type of lung cancer cells in about 8.2 (28/343) patients was unknown. Among the surgical patients, 21 patients underwent minimally invasive surgery (14.0%), 28 patients underwent simple decompression surgery (18.7%), 76 patients underwent separation surgery (50.7%), and 25 patients underwent radical surgery (16.6%). 59.3% (89/150) of the patients had a better neurological function than before surgery. The average survival time of all patients was 9.88 months with the median survival time of 8 (5,14) months. The survival rates were 62.1% (213/343), 30.0% (103/343), and 3.8% (13/343) at 6, 12, and 24 months, respectively. The average survival time of patients in the operation group was 10.24 months with the median survival time of 9 (5, 15) months, and the average survival time of patients in the non operation group was 9.41 months with the median survival time of 7 (5, 13) months with no significant difference between the groups (χ 2=0.300, P=0.584). Multivariate Cox proportional hazard regression model analysis showed that radiotherapy [ HR=1.913, 95% CI(1.471, 2.488), P<0.001], chemotherapy [ HR=1.313, 95% CI(1.040, 1.658), P=0.022], targeted drug therapy [ HR=1.683, 95% CI(1.221, 2.319), P=0.001], KPS [ HR=1.593, 95% CI(1.140, 2.225), P=0.006] and pathological type (non-small cell lung cancer) were independent factors affecting the 1-year survival rate of patients with spinal metastasis secondary to lung cancer [ HR=0.322, 95% CI(0.225, 0.460), P<0.001] with significant difference. Conclusion:Surgical treatment can improve both the neurological function and general status of patients with spinal metastasis. Treatments of radiotherapy, chemotherapy, and targeted drug therapy can significantly improve 1-year survival rate, while a KPS less than 50 points and a primary lung cancer other than adenocarcinoma were independent risk factors reducing 1-year survival rate.

Background::Pulmonary arterial hypertension (PAH) is characterized by excessive proliferation of small pulmonary arterial vascular smooth muscle cells (PASMCs), endothelial dysfunction, and extracellular matrix remodeling. G protein-coupled receptor kinase 2 (GRK2) plays an important role in the maintenance of vascular tone and blood flow. However, the role of GRK2 in the pathogenesis of PAH is unknown.Methods::GRK2 levels were detected in lung tissues from healthy people and PAH patients. C57BL/6 mice, vascular smooth muscle cell-specific Grk2-knockout mice ( Grk2?SM22), and littermate controls ( Grk2flox/flox) were grouped into control and hypoxia mice ( n = 8). Pulmonary hypertension (PH) was induced by exposure to chronic hypoxia (10%) combined with injection of the SU5416 (cHx/SU). The expression levels of GRK2 and Yes-associated protein (YAP) in pulmonary arteries and PASMCs were detected by Western blotting and immunofluorescence staining. The mRNA expression levels of Grk2 and Yes-associated protein ( YAP) in PASMCs were quantified with real-time polymerase chain reaction (RT-PCR). Wound-healing assay, 3-(4,5)-dimethylthiahiazo (-z-y1)-3,5-di-phenytetrazoliumromide (MTT) assay, and 5-Ethynyl-2′-deoxyuridine (EdU) staining were performed to evaluate the proliferation and migration of PASMCs. Meanwhile, the interaction among proteins was detected by immunoprecipitation assays. Results::The expression levels of GRK2 were upregulated in the pulmonary arteries of patients with PAH and the lungs of PH mice. Moreover, cHx/SU-induced PH was attenuated in Grk2?SM22 mice compared with littermate controls. The amelioration of PH in Grk2?SM22 mice was accompanied by reduced pulmonary vascular remodeling. In vitro study further confirmed that GRK2 knock-down significantly altered hypoxia-induced PASMCs proliferation and migration, whereas this effect was severely intensified by overexpression of GRK2. We also identified that GRK2 promoted YAP expression and nuclear translocation in PASMCs, resulting in excessive PASMCs proliferation and migration. Furthermore, GRK2 is stabilized by inhibiting phosphorylating GRK2 on Tyr86 and subsequently activating ubiquitylation under hypoxic conditions. Conclusion::Our findings suggest that GRK2 plays a critical role in the pathogenesis of PAH, via regulating YAP expression and nuclear translocation. Therefore, GRK2 serves as a novel therapeutic target for PAH treatment.

Objective To screen the anti-Helicobacter pylori gastritis active components of the ethyl acetate extract of Alpinia officinarum Hance.Methods The"knock-out"strategy combined with high-performance liquid chromatography(HPLC)detection was developed to separate the components of the ethyl acetate extract of A.officinarum while obtaining the negative samples without the components.A human gastric epithelial cell(GES-1)model of H.pylori gastritis was established,and the levels of interleukin-6(IL-6),tumor necrosis factor-α(TNF-α),interleukin-8(IL-8)and interleukin-1β(IL-1β)in the supernatant of the cells were determined by enzyme-linked immunosorbent assay(ELISA).Results The total flavonoid fraction,the negative fraction without total diphenylheptanoids,the negative fraction without 5-hydroxy-7-(4-hydroxy-3-methoxyphenyl)-1-phenyl-3-heptanone(DHPA),and galangin significantly reduced IL-6 levels in the supernatant of H.pylori infected GES-1 cells at a concentration of 8 μg·mL-1 with 24 h incubation.The total flavonoid fraction strongly inhibited the release of IL-6,TNF-α,IL-8,and IL-1β from H.pylori gastritis GES-1 cells at a concentration of 16 μg·mL-1.Conclusions The total flavonoid fraction is the major anti-H.pylori gastritis active component of the ethyl acetate extract of A.officinarum.The results lay the foundation for further elucidation of the material basis of A.officnarum against H.pylori gastritis.