ObjectiveTo explore the pharmacological mechanism involved in the treatment of allergic cough （AC） by Xiaoer Huatan Zhike granules （XEHT） based on proteomics and network pharmacology. MethodsAfter sensitization by intraperitoneal injection of 1 mL suspension containing 2 mg ovalbumin （OVA） and 100 mg aluminum hydroxide， a guinea pig model of allergic cough was constructed by nebulization with 1% OVA. The modeled guinea pigs were randomized into the model， low-， medium- and high-dose （1， 5， 20 g·kg^-1， respectively） XEHT， and sodium montelukast （1 mg·kg^-1） groups （n=6）， and another 6 guinea pigs were selected as the blank group. The guinea pigs in drug administration groups were administrated with the corresponding drugs by gavage， and those in the blank and model groups received the same volume of normal saline by gavage， 1 time·d^-1. After 10 consecutive days of drug administration， the guinea pigs were stimulated by 1% OVA nebulization， and the coughs were observed. The pathological changes in the lung tissue were observed by hematoxylin-eosin staining. The enzyme-linked immunosorbent assay was performed to measure the levels of C-reactive protein （CRP）， interleukin-6 （IL-6）， tumor necrosis factor-α （TNF-α）， superoxide dismutase （SOD）， and malondialdehyde （MDA） in the bronchoalveolar lavage fluid （BALF） and immunoglobulin G （IgG） and immunoglobulin A （IgA） in the serum. Immunohistochemistry （IHC） was employed to observe the expression of IL-6 and TNF-α in the lung tissue. Transmission electron microscopy was employed observe the alveolar type Ⅱ epithelial cell ultrastructure. Real-time PCR was employed to determine the mRNA levels of IL-6， interleukin-1β （IL-1β）， and TNF-α in the lung tissue. Label-free proteomics was used to detect the differential proteins among groups. Network pharmacology was used to predict the targets of XEHT in treating AC. The Kyoto Encyclopedia of Genes and Genomes （KEGG） enrichment analysis was performed to search for the same pathways from the results of proteomics and network pharmacology. ResultsCompared with the blank group， the model group showed increased coughs （P<0.01）， elevated levels of CRP， TNF-α， IL-6， and MDA and lowered level of SOD in the BALF （P<0.05， P<0.01）， elevated levels of IgA and IgG in the serum （P<0.05， P<0.01）， congestion of the lung tissue and infiltration of inflammatory cells， increased expression of IL-6 and TNF-α （P<0.01）， large areas of low electron density edema in type Ⅱ epithelial cells， obvious swelling and vacuolization of the organelles， karyopyknosis or sparse and dissolved chromatin， and up-regulated mRNA levels of IL-6， IL-1β， and TNF-α （P<0.01）. Compared with the model group， the drug administration groups showed reduced coughs （P<0.01）， lowered levels of CRP， TNF-α， IL-6， and MDA and elevated level of SOD in the BALF （P<0.05， P<0.01）， alleviated lung tissue congestion， inflammatory cell infiltration， and type Ⅱ epithelial cell injury， and decreased expression of IL-6 and TNF-α （P<0.01）. In addition， the medium-dose XEHT group and the montelukast sodium group showcased lowered serum levels of IgA and IgG （P<0.05， P<0.01）. The medium- and high-dose XEHT groups and the montelukast sodium showed down-regulated mRNA levels of IL-6， IL-1β， and TNF-α and the low-dose XEHT group showed down-regulated mRNA levels of IL-6 and TNF-α （P<0.05， P<0.01）. Phospholipase D， mammalian target of rapamycin （mTOR）， and epidermal growth factor receptor family of receptor tyrosine kinase （ErbB） signaling pathways were the common pathways predicted by both proteomics and network pharmacology. ConclusionProteomics combined with network pharmacology reveal that XEHT can ameliorate AC by regulating the phospholipase D， mTOR， and ErbB signaling pathways.

Hypoxemia is a common pathological state characterized by low oxygen saturation in the blood. This condition compromises mucosal barrier integrity particularly in the gut and oral cavity. However, the mechanisms underlying this association remain unclear. This study used periodontitis as a model to investigate the role of platelet activation in oral mucosal immunopathology under hypoxic conditions. Hypoxia upregulated methyltransferase-like protein 4 (METTL4) expression in platelets, resulting in N⁶-methyladenine modification of mitochondrial DNA (mtDNA). This modification impaired mitochondrial transcriptional factor A-dependent cytosolic mtDNA degradation, leading to cytosolic mtDNA accumulation. Excess cytosolic mt-DNA aberrantly activated the cGAS-STING pathway in platelets. This resulted in excessive platelet activation and neutrophil extracellular trap formation that ultimately exacerbated periodontitis. Targeting platelet METTL4 and its downstream pathways offers a potential strategy for managing oral mucosa immunopathology. Further research is needed to examine its broader implications for mucosal inflammation under hypoxic conditions.
DNA, Mitochondrial/metabolism* ; Mouth Mucosa/pathology* ; Hypoxia/immunology* ; Methyltransferases/metabolism* ; Blood Platelets/metabolism* ; Animals ; Periodontitis/immunology* ; Humans ; Platelet Activation ; Mice

The in vitro release is an important index to evaluate the quality of liposome formulation.Currently, there is no evaluation method for the in vitro release of liposome in pharmacopoeia of various countries, which leads to the lack of unified standard and safety guarantee for the quality evaluation of liposome formulation.Taking the self-made paclitaxel derivative liposomes as an example, the paddle membrane binding method established by optimizing external release conditions was used to simulate the complete release of paclitaxel derivative drugs in 12 hours under physiological conditions.The results showed that using 0.5% SDS-HEPES as the release medium and a dialysis bag with a molecular weight cutoff of 1 000 kD to release the liposome solution met the requirements and had discrimination ability, providing a reference for the development of drug-loaded liposomes release methods in vitro.

Tinnitus refers to the perception of abnormal sound in the absence of external sound stimulation. It can have an impact on a person's mood, memory, attention, and mental state, although the mechanism of tinnitus is still unclear. In recent years, the research on the central neural mechanism of tinnitus has attracted the attention of scholars.Functional magnetic resonance imaging （fMRI）,as an effective imaging technology, has been actively employed in this field. This paper provides a systematic summary of studies on the central neural mechanism of tinnitus by fMRI in recent years,revealed the changes of functional connections among tinnitus-related neural networks,such as auditory network,limbic system,default mode network and salience network. The central neural mechanism of tinnitus involves multiple networks that interact with each other. By understanding this mechanism, we hope to develop more targeted prevention and treatment strategies to help patients alleviate long-term tinnitus.
Humans ; Tinnitus/diagnostic imaging* ; Magnetic Resonance Imaging/methods* ; Attention

Patients with impaired quality of life associated with xerostomia need long-term treatment, and a nerve stimulator has the advantage of providing natural saliva and long-term management for patients with xerostomia by electrically stimulating the relevant secretory nerves to promote saliva production. A number of clinical trials have preliminarily demonstrated the efficacy of nerve electrical stimulation in the treatment of xerostomia. However, electrical stimulation has not yet become the mainstream treatment for xerostomia. Large prospective randomized controlled clinical trials are still needed to confirm its long-term effectiveness and safety. In addition, the design of nerve stimulators is of great significance for clinical application. The large volume and inconvenient treatment associated with the extra oral nerve stimulator and the first generation intraoral nerve stimulator hinder their clinical application and popularization. The second- and third-generation intraoral nerve stimulator devices are small, convenient to use and have great application prospects. Research on electrical nerve stimulators for xerostomia treatment is mainly concentrated in European and American countries, while there is very little domestic research. It is urgent to master the core technology for the research and development of electrical nerve stimulators. The innovation of miniaturization, efficient power supply, data feedback and packaging will be the key issues of electrical nerve stimulators in the future. In this paper, the treatment and research of electrical nerve stimulation for xerostomia are reviewed to provide a reference for related basic research and the clinical application of electrical stimulators treating xerostomia in China.

Cbf-14 is a novel antimicrobial peptide composed of 14 amino acids.An optimized reversed phase high-performance liquid chromatographic method with electrospray-ionization quadrupole time-of-flight mass spectrometer (LC-ESI-QTOF/MS) method was developed for separation, identification and characterization of structurally related peptide impurities in Cbf-14 gel.Chromatographic separation was carried out on an Agilent ZORBAX SB-Phenyl column (150 mm × 4.6 mm, 3.5 μm), with acetonitrile-20 mmol/L ammonium formate buffer (adjusted to pH 3.0 with formic acid) as eluent using gradient elution.Under the established conditions, Cbf-14 and its structurally related peptide impurities were well separated; and a total of 24 impurities were detected and identified, of which 5 were impurities in the preparation manufacturing process and 19 were stressed products.Based on high resolution mass spectrometry analysis, the origins and formation mechanisms of these impurities were located.The obtained results are useful for the establishment of the manufacturing process, storage condition and quality control of Cbf-14 gel.

【Objective】 To investigate the effect of polymerized human cord hemoglobin (PolyCHb) on the chemosensitivity of human breast cancer MCF-7 cell subcutaneous xenografts in nude mice and its mechanism. 【Methods】 The MCF-7 cells in exponential growth phase were collected and made into suspension cells at a density of 5×10⁷ cells/mL.Subsequently, the cells were inoculated subcutaneously in the right limb of 18 BALB/c-nu nude mice with 0.2 mL cells per mouse to establish subcutaneous xenograft.When the tumor volume reached about 100 mm³, they were randomly divided into chemotherapy group: doxorubicin 5 mg·kg^-1, once/week; chemotherapy + PolyCHb group: in addition to doxorubicin (chemotherapy group), PolyCHb 600 mg·kg^-1, 3 times/week; the control group: normal saline 90 mg·kg^-1, once/week; all were injected through tail vein continuously for 4 weeks.From the day of injection (d 0), the tumor volume of each group of nude mice was measured every 3 days, and the tumor growth curves were drawn accordingly.After 38 days, the tumor growth observation was completed.The tumor was removed and weighed to calculate the tumor inhibition rate.HE staining, immunohistochemistry and TUNEL method were used to observe the pathological changes of tumor tissue, detect the expression of HIF-1α, and detect tumor cell apoptosis respectively.The content of reactive oxygen species (ROS) of each group was determined by fluorescence staining. 【Results】 The tumor volume (mm³) of chemotherapy + PolyCHb group, chemotherapy group and the control group at day 38 were 196.35±103.45 vs 316.29±62.88 vs 519.42±177.33 (P<0.05), and the tumor inhibition rate (%) of chemotherapy + PolyCHb treatment group and chemotherapy group was 62.20 vs 39.11, respectively.HE staining and TUNEL detection showed that cell necrosis and apoptosis in the growth area of tumor tissue increased in chemotherapy + PolyCHb group.Immunohistochemistry and fluorescence staining showed that HIF-1α expression in chemotherapy + PolyCHb group decreased and reactive oxygen species (ROS) content increased. 【Conclusion】 PolyCHb increases the chemosensitivity of subcutaneous xenograft in nude mice with breast cancer, and its mechanism may be related to the increase of ROS in tumor tissue and the promotion of tumor cell apoptosis.

Objective:To evaluate the clinical value of the transcutaneous neuromodulation (TN) in improving gastrointestinal function after gastrointestinal tumor operation.Methods:From April 2019 to June 2020, at The Affiliated People′s Hospital of Ningbo University, 100 patients who underwent gastrointestinal tumor surgery were included. The 100 patients were randomly divided into treatment group(receiving TN treatment, 50 cases)and control group (receiving sham TN treatment, 50 cases). The clinical data of the two groups was compared to evaluate the recovery of gastrointestinal function, which included the time of first defecation, time of first flatus, time of first ambulation, time of resuming diet, the incidence of nausea and vomiting within 3 d after operation and pain score (0 to 10). Heart rate variability (HRV) was compared between two groups to analyze the possible mechanism of TN improving gastrointestinal function after gastrointestinal tumor surgery. Independent sample t test and Chi-square test were used for statistical analysis. Results:Among 100 patients, there were 63 male and 37 female patients, the age was (67.0±11.3) years old, ranged from 28 to 92 years old. Compared with the control group, the time of first defecation, first flatus, first ambulation and resuming diet of treatment group reduced by 31.0%, 39.8%, 38.0% and 32.4% ((72.1±3.0) h vs.(104.5±2.9) h, (49.4±5.7) h vs.(82.1±3.1) h, (3.1±0.7) d vs.(5.0±0.9) d, (4.8±0.9) d vs. (7.1±0.8) d)), respectively; the pain scores on the day 2 and day 3 after operation and incidence of nausea and vomiting within 3 d after operation decreased by 50.0%, 65.5%, 26.0%(1.5±0.6 vs. 3.0±0.7, 1.0±0.6 vs. 2.9±0.6, 16.0%, 8/50 vs. 42.0%, 21/50), respectively, and the differences were statistically significant ( t=54.28, 35.72, 11.67, 13.66, 12.00 and 14.90, χ2=8.21, all P<0.01). The results of HRV analysis showed that the high frequency on day 3 was higher than that on day 1 of treatment group, and the ratio of low frequency to high frequency after operation was lower than that before operation of treatment group (0.5±0.1 vs. 0.4±0.1, 1.2±0.7 vs. 1.9±1.0), and the differences were statistically significant( t=-4.81 and 4.26, both P<0.01), which indicated TN could enhance vagal activity. Conclusions:TN promote the recovery of gastrointestinal function after gastrointestinal tumor operation, and can be used as an adjuvant therapy to accelerate the recovery of gastrointestinal function after gastrointestinal tumor operation.

Contrast induced nephropathy (CIN) is acute renal injury following administration of contrast media during angiographic or other medical procedures, which represents as the third cause of hospital-acquired renal failure. CIN is associated with prolonged hospital stay, increased health-care costs, and undesirable clinical outcome. The risk of CIN includes advanced age and diabetes mellitus. With the rapid development of iconography and the wide application of interventional techniques, the patients with CIN are increasing. The preventive measures of CIN include hydration, using appropriate contrast media, stopping nephrotoxic drugs, ischemic preconditioning, renal replacement therapy, and using appropriate drugs. In this paper, the current status and early prevention progress of CIN will be reviewed from three aspects of the high-risk factors, pathogenesis and prevention, aiming to provide guidance for the early prevention of CIN and explore new research directions.

Contrast induced nephropathy (CIN) is acute renal injury following administration of contrast media during angiographic or other medical procedures, which represents as the third cause of hospital-acquired renal failure. CIN is associated with prolonged hospital stay, increased health-care costs, and undesirable clinical outcome. The risk of CIN includes advanced age and diabetes mellitus. With the rapid development of iconography and the wide application of interventional techniques, the patients with CIN are increasing. The preventive measures of CIN include hydration, using appropriate contrast media, stopping nephrotoxic drugs, ischemic preconditioning, renal replacement therapy, and using appropriate drugs. In this paper, the current status and early prevention progress of CIN will be reviewed from three aspects of the high-risk factors, pathogenesis and prevention, aiming to provide guidance for the early prevention of CIN and explore new research directions.
Acute Kidney Injury ; Angiography ; Contrast Media ; Humans ; Ischemic Preconditioning ; Kidney Diseases ; Renal Replacement Therapy ; Risk Factors