This study explores the therapeutic differences and mechanisms of salt-processed Phellodendri Chinensis Cortex in improving insulin resistance(IR) based on network pharmacology, molecular docking, and cellular experiments. The components and intersection targets of Phellodendri Chinensis Cortex in improving IR were collected from databases, and a "drug-component-target-disease" network and protein-protein interaction(PPI) network were constructed to screen core components and targets. A total of 29 active components and 240 intersection targets were identified, of which 13 were core targets. Gene Ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analyses were used to identify key signaling pathways, and molecular docking was performed to validate the binding activity between core components and targets. An IR model in HepG2 cells was induced using insulin combined with high glucose, and the effects of Phellodendri Chinensis Cortex before and after salt-processing on cell glucose consumption were evaluated. The expression of proteins related to the mitogen-activated protein kinase(MAPK) and phosphatidylinositol 3-kinase(PI3K)-protein kinase B(AKT) signaling pathways was detected by Western blot. The cellular experimental results showed that, compared with the model group, glucose consumption in the drug-treated groups was significantly increased(P<0.01), the phosphorylation level of extracellular regulated protein kinase(ERK) was decreased(P<0.05), the phosphorylation levels of PI3K and AKT were increased, and the expression of glucose transporter 4(GLUT4) was also upregulated(P<0.05). Furthermore, the effect of salt-processed Phellodendri Chinensis Cortex was better than that of raw Phellodendri Chinensis Cortex. The study demonstrates that Phellodendri Chinensis Cortex, both before and after salt-processing, improves IR by regulating the expression of related proteins in the MAPK and PI3K-AKT signaling pathways, with enhanced effects after salt-processing.
Humans ; Network Pharmacology ; Phellodendron/chemistry* ; Insulin Resistance ; Drugs, Chinese Herbal/chemistry* ; Hep G2 Cells ; Signal Transduction/drug effects* ; Molecular Docking Simulation ; Protein Interaction Maps/drug effects* ; Proto-Oncogene Proteins c-akt/genetics* ; Phosphatidylinositol 3-Kinases/genetics* ; Glucose/metabolism*

Objective To explore the relationship between blood glucose variability, disease severity and prognosis of the patients with acute pancreatitis. Methods Total of 242 patients with acute pancreatitis admitted to the department of emergency from January 2019 to December 2019 were enrolled. The organ failure was evaluated according to Marshall's score, the severity of the disease was evaluated according to Atlanta's score, and the blood glucose indexes of three groups of patients with mild acute pancreatitis, moderate severe acute pancreatitis and severe acute pancreatitis were compared within seven days after admission. The relationship between blood glucose index and disease severity in different patients with acute pancreatitis was analyzed. Taking whether a puncture was performed at admission, whether the patient was admitted to the intensive care unit (ICU), and whether the patient died as endpoint events as classification factors, the relationship between blood glucose indicators and disease prognosis of patients with acute pancreatitis was analyzed using the One-Way ANOVA, Kruskal-Wallis test, Mann-Whitney U test, receiver operating characteristic curve (ROC curve), etc. Results Of the 242 patients, 70 cases (28.9%) were mild acute pancreatitis, 71 cases (29.3%) with moderate severe acute pancreatitis, 101 cases (41.7%) with severe acute pancreatitis. There was no statistically significant difference in the coefficient of variation of blood glucose among the three groups within 7 days of admission. The mean, standard deviation, maximum, minimum value and difference between maximum and minimum value of venous blood glucose in severe acute pancreatitis group were higher than those in moderate severe acute pancreatitis group, while those in moderate severe acute pancreatitis group were higher than those in mild acute pancreatitis group. The mean value of blood glucose of invasive operation group (IOP) (n=55) was higher than that of non-invasive operation (NOP) group(n=187). Conclusions The blood glucose level and fluctuation range of patients with acute pancreatitis within seven days after admission, are of great significance for the judgment of the severity and prognosis of the disease.

Objective:To explore the predictive value of neutrophil-to-lymphocyte ratio (NLR) and tumor necrosis factor -α (TNF-α) level on the therapeutic effect of transcatheter arterial chemoembolization (TACE) combined with microwave ablation in patients with massive liver cancer.Methods:The medical records of 106 patients with massive liver cancer who underwent TACE combined with microwave ablation treatment in the Affiliated Hospital of Weifang Medical University from February 2020 to February 2023 were retrospectively analyzed. The efficacy was evaluated 6 weeks after surgery, and the patients were divided into remission group and non-remission group according to the therapeutic effect. The levels of NLR and TNF-α in the two groups were detected before surgery, 3 days after surgery and 7 days after surgery. Point two column correlation was used to analyze the relationship between the levels of NLR and TNF-α in different time periods and the therapeutic effect of TACE combined with microwave ablation in patients with massive liver cancer. The receiver operator characteristic (ROC) curve was drawn to analyze the predictive value of NLR and TNF-α levels in different time periods for the therapeutic effect of TACE combined with microwave ablation in patients with massive liver cancer.Results:Six weeks after surgery, out of 106 patients with massive liver cancer, 13 achieved complete remission, 48 achieved partial remission, 20 experienced disease progression, and 25 remained stable. The overall remission rate was 57.55% (61/106). Before surgery, the levels of NLR [ (2.26±0.13) vs. (2.43±0.12), t=6.87, P<0.001] and TNF-α [ (36.20±4.38) pg/ml vs. (42.74±5.74) pg/ml, t=6.66, P<0.001] in the remission group ( n=61) were lower than those in the non-remission group ( n=45), with statistically significant differences. At 3 days after surgery, there were no statistically significant difference in the levels of NLR [ (6.16±3.22) vs. (6.22±3.30), t=0.09, P=0.925] or TNF-α [ (48.84±7.22) pg/ml vs. (49.13±7.34) pg/ml, t=0.20, P=0.840] between the remission group and the non-remission group. At 7 days after surgery, the levels of NLR [ (2.60±0.18) vs. (2.82±0.26), t=5.15, P<0.001] and TNF-α [ (38.20±6.30) pg/ml vs. (45.57±5.79) pg/ml, t=6.16, P<0.001] in the remission group were lower than those in the non-remission group, with statistically significant differences. There were statistically significant differences in NLR and TNF-α levels before surgery, 3 days and 7 days after surgery between the remission group and the non-remission group ( F=82.43, P<0.001; F=54.45, P<0.001; F=76.23, P<0.001; F=15.61, P<0.001). Further pair-to-pair comparison showed that the levels of NLR and TNF-α were higher in both groups 3 and 7 days after surgery than before surgery, but the levels of NLR and TNF-α were lower in both groups 7 days after surgery than 3 days after surgery, with statistically significant differences (all P<0.005). Point two column correlation analysis showed that NLR level, TNF-α level and the efficacy of TACE combined with microwave ablation in patients with massive liver cancer were significantly positively correlated before and 7 days after surgery ( r=0.42, P<0.001; r=0.49, P<0.001; r=0.43, P<0.001; r=0.46, P<0.001). ROC curve showed that the area under the curve (AUC) of NLR and TNF-α alone in predicting the efficacy of TACE combined with microwave ablation in patients with massive liver cancer before and 7 days after surgery was 0.750 (95% CI: 0.656-0.844), 0.788 (95% CI: 0.699-0.877), 0.751 (95% CI: 0.652-0.850), 0.788 (95% CI: 0.700-0.876), respectively. The AUC of combined prediction of NLR and TNF-α before and 7 days after surgery were 0.818 (95% CI: 0.736-0.900) and 0.813 (95% CI: 0.730-0.897), respectively. There were no statistically significant differences in the AUC values of NLR and TNF-α alone or in combination for predicting the therapeutic effect of TACE combined with microwave ablation in patients with massive liver cancer before and 7 days after surgery (all P>0.05) . Conclusions:The levels of NLR and TNF-α before and 7 days after surgery are related to the effect of TACE combined with microwave ablation in patients with massive liver cancer, and the combination of NLR and TNF-α levels before and 7 days after surgery has certain value in predicting the effect of TACE combined with microwave ablation in patients with massive liver cancer.

Sonogenetics is an emerging synthetic biology technique that uses sound waves to activate mechanosensitive ion channel proteins on the cell surface to regulate cell behavior and function.Due to the widespread presence of mechanically sensitive ion channel systems in cells and the advantages of non-invasion,strong penetrability,high safety and high accuracy of sonogenetics technology,it has great development potential in basic biomedical research and clinical applications,especially in neuronal regulation,tumor mechanism research,sonodynamic therapy and hearing impairment.This review discusses the basic principles of sonogenetics,the development status of sonogenetics and its application in the prevention and treatment of noise-induced hearing loss,summarizes and analyzes the current challenges and future development direction,thus providing a reference for further research and development of sonogenetics in the field of military medicine.

Objective To develop a portable field infusion kit for first aid to meet the treatment requirements in field conditions.Methods The infusion kit had its frame made of third-generation carbon fiber material and was composed of a lid and a body.The lid was equipped with embedded handles on the outer surface,a medicine module consisting of 12 mesh bags on the inner surface and LED lights on the inner and outer front side walls.The kit body had three storage layers in its upper,middle and lower parts,of which the upper layer was for supplies of infusion and hemostatic dressing,the middle layer was for medical instruments and soft bags of liquid for first aid,and the lower layer was for medical waste and sharp instruments,and the bottom of the kit was provided with telescopic drawbars and invisible rollers.Results The first-aid infusion kit facilitated the storage and utilization of kinds of infusion supplies,and lowered time consumption and workloads for transport.Conclusion The first-aid infusion kit gains advantages in reasonable layout,comprehensive functions and convenient operation,and thus is worhty promoting for casualty treatment in field conditions.[Chinese Medical Equipment Journal,2024,45(7):115-117]

Aim To investigate the intracellular up-take and target protein binding characteristics of two Bruton's tyrosine kinase inhibitors(BTKi)with differ-ent selectivities to provide further insights into the mechanisms of drug off-target-related bleeding risk.Methods Ibrutinib(non-selective BTKi)and za-nubrutinib(selective BTKi)were used as study drugs.After incubation of MEC-1 cells and human platelets with drugs,the cellular thermal shift assay(CETSA)was combined with Western blot to obtain the melting curve and isothermal curve to analyze the binding char-acteristics of the two drugs with the target protein BTK.After incubation of MEC-1 cells and human platelets with drugs,the concentrations of the two drugs were detected by liquid chromatography-tandem mass spectrometry(LC-MS/MS)to analyze the intracellular uptake of the two drugs.Results CETSA analysis confirmed that zanubrutinib was more selective for the target protein BTK compared to ibrutinib.LC-MS/MS analysis showed that both drugs were uptaken intracel-lularly by MEC-1 cells and platelets in a concentration-dependent manner.Conclusions While BTKi targe-ting BTK to B lymphocytes exerts therapeutic effects,off-target effects on platelets due to differences in their intracellular uptake,and target-binding characteristics may be one of the reasons for the differences in bleed-ing risk across selective BTKi.

Abstract Allergic diseases can occur in all systems of the body, covering the whole life cycle, from children to adults and to old age, can be lifelong onset and even fatal in severe cases. Children account for the largest proportion of the victims of allergic disease, Children s allergies start from scratch, ranging from mild to severe, from less to more, from single to multiple systems and systemic performance, so the prevention and treatment of allergic diseases in children is of great importance, which can not only prevent high risk allergic conditions from developing into allergic diseases, but also further block the process of allergy. At present, there is no consensus on the management system of allergic children in kindergartens and primary schools. The "Consensus on Allergy Management and Prevention in Kindergartens and Primary Schools", which includes the organizational structure, system construction and management of allergic children, provides evidence informed recommendations for the long term comprehensive management of allergic children in kindergartens and primary schools, and provides a basis for the establishment of the prevention system for allergic children.

Objective: This study aims to investigate the associations between genetic variations of pyroptosis pathway related key genes and adverse events (AEs) of postoperative chemoradiotherapy (CRT) in patients with rectal cancer. Methods: DNA was extracted from the peripheral blood which was collected from 347 patients before CRT. Sequenom MassARRAY was used to detect the genotypes of 43 haplotype-tagging single nucleotide polymorphisms (htSNPs) in eight pyroptosis genes, including absent in melanoma 2 (AIM2), caspase-1 (CASP1), caspase-4(CASP4), caspase-5 (CASP5), caspase-11 (CASP11), gasdermin D (GSDMD), gasdermin E (GSDME) and NLR family pyrin domain containing 3 (NLRP3). The associations between 43 htSNPs and AEs were evaluated by the odd ratios (ORs) and 95% confidence intervals (CIs) by unconditional logistic regression models, adjusted for sex, age, clinical stage, tumor grade, Karnofsky performance status (KPS), surgical procedure, and tumor location. Results: Among the 347 patients with rectal cancer underwent concurrent CRT with capecitabine after surgery, a total of 101(29.1%) occurred grade ≥ 2 leukopenia. rs11226565 (OR=0.41, 95% CI: 0.21-0.79, P=0.008), rs579408(OR=1.54, 95% CI: 1.03-2.29, P=0.034) and rs543923 (OR=0.63, 95% CI: 0.41-0.98, P=0.040) were significantly associated with the occurrence of grade ≥ 2 leukopenia. One hundred and fifty-six (45.0%) had grade ≥ 2 diarrhea, two SNPs were significantly associated with the occurrence of grade ≥ diarrhea, including CASP11 rs10880868 (OR=0.55, 95% CI: 0.33-0.91, P=0.020) and GSDME rs2954558 (OR=1.52, 95% CI: 1.01-2.31, P=0.050). In addition, sixty-six cases (19.0%) developed grade ≥2 dermatitis, three SNPs that significantly associated with the risk of grade ≥2 dermatitis included GSDME rs2237314 (OR=0.36, 95% CI: 0.16-0.83, P=0.017), GSDME rs12540919 (OR=0.52, 95% CI: 0.27-0.99, P=0.045) and NLRP3 rs3806268 (OR=1.51, 95% CI: 1.03-2.22, P=0.037). There was no significant difference in the association between other genetic variations and AEs of rectal cancer patients (all P>0.05). Surgical procedure and tumor location had great impacts on the occurrence of grade ≥2 diarrhea and dermatitis (all P<0.01). Conclusion: The genetic variants of CASP4, CASP11, GSDME and NLRP3 are associated with the occurrence of AEs in patients with rectal cancer who received postoperative CRT, suggesting they may be potential genetic markers in predicting the grade of AEs to achieve individualized treatment of rectal cancer.
Humans ; Pyroptosis ; NLR Family, Pyrin Domain-Containing 3 Protein/metabolism* ; Gasdermins ; Chemoradiotherapy/adverse effects* ; Rectal Neoplasms/surgery* ; Caspases/metabolism* ; Diarrhea/chemically induced* ; Leukopenia/genetics* ; Genetic Variation ; Dermatitis

ObjectiveTo investigate the analgesic action and mechanism of intrathecal 2R， 6R-hydroxynorketamine （2R， 6R-HNK） on spared nerve injury （SNI）-induced chronic neuropathic pain （CNP） in female mice. MethodsSNI was used to establish acute and chronic CNP models in female mice. The mice were randomly divided into different groups with administration of vehicle， 2R， 6R-HNK or S-ketamine （10 mg/kg intraperitoneal injection/i.p. or 7， 21 μmol/L intrathecal injection/i.t.） at 3 weeks after or 30 min/1 d before operation （n = 3 - 7 mice/group）. The curative or preventive effect of 2R， 6R-HNK was evaluated by mechanical paw withdrawal threshold （PWT） and the analgesic efficiency. Finally， immunofluorescence and RT-PCR of dorsal root ganglion （DRG） and spinal dorsal horn （SDH） were used to explore the possible mechanisms. ResultsCompared with vehicle， intrathecal injection of 2R， 6R-HNK largely reversed SNI-induced bilateral mechanical allodynia in a delayed-and-dose-dependent way. Among them， 21 μmol/L 2R， 6R-HNK reached its maximum analgesic efficiency （75.32±7.69） % at 2 d. Pre-intrathecal delivery of 2R， 6R-HNK also delayed the development of bilateral mechanical hypersensitivity 2 - 3 d induced by SNI. Mechanically， 2R， 6R-HNK reversed not only the abnormal excitability of neurons in bilateral DRG and superficial SDH， but also the upregulation of calcitonin gene-related peptide （CGRP） and brain-derived nerve growth factor （BDNF） in DRG. ConclusionIntrathecal administration of 2R， 6R-HNK exerts an analgesic effect against CNP， probably via suppressing abnormal neuronal excitability in ascending pain pathway as well as down-regulating CGRP and BDNF expression in DRG neurons.

ABSTRACT OBJECTIVE To investigate the effects and mechanism of ginsenoside Rh2 on the proliferation and apoptosis in human glioma U87 and U251 cells. METHODS Using human glioma U87 and U251 cells as subjects， the proliferation and apoptosis， as well as the expression of histone deacetylase 1（HDAC1） protein and apoptosis-related proteins [B cell lymphoma-2（Bcl-2）， Bcl-2-associated X protein （Bax） and cleaved caspase-3] were detected after being treated with different concentrations of ginsenoside Rh2. RESULTS The concentrations of 10，20，30，40，50，60，70，80 μmol/L ginsenoside Rh2 could generally significantly increase the proliferation inhibition rate of U87 and U251 cells （P＜0.05 or P＜0.01）， and the half inhibitory concentrations of this component after 48 hours of action were 51.34 and 55.84 μmol/L， respectively；30，50 μmol/L ginsenoside Rh2 could increase the total apoptotic rate of both types of cells， reduced the protein expressions of HDAC1 and Bcl-2， and increased the protein expressions of Bax and cleaved caspase-3 significantly （P＜0.05 or P＜0.01）. CONCLUSIONS Ginsenoside Rh2 has a significant inhibitory effect on the proliferation of glioma cells and promotes the apoptosis of cells， which may be through reducing the expression of HDAC1 protein and activating the Bcl-2 family protein-mediated apoptosis pathway.