OBJECTIVE To explore the improvement effects of Suting pingchuan decoction （STPC） on bronchial asthma in rats and its potential mechanism. METHODS Male SD rats were randomly divided into blank group， model group， STPC low-， medium- and high-dose groups （4.14， 8.28， and 16.56 g/kg， respectively， based on the crude drug dosage）， and dexamethasone group （positive control， 1 mg/kg）， with 8 rats in each group. Except for the blank group， the other groups were sensitized by intraperitoneal injection of ovalbumin and challenged by nebulized inhalation of ovalbumin to establish a bronchial asthma model. From the day of nebulization challenge， rats of each group were administered the corresponding drug solution or normal saline by gavage 1 hour before aerosolization， once a day， for 7 consecutive days. During the experiment， behavioral changes in rats of each group were observed. After the last administration， the levels of inflammatory factors （interleukin-1β， interleukin-18） in bronchoalveolar lavage fluid （BALF）， and oxidative stress indexes [malondialdehyde （MDA）， superoxide dismutase （SOD）] in lung tissue were determined； pathological changes in lung tissue were observed； cell apoptosis in lung tissue， and the mRNA expression of nucleotide-binding domain leucine-rich repeat and pyrin domain-containing receptor 3 （NLRP3） and the protein expressions of NLRP3， cleaved caspase-1， caspase-1， gasdermin D （GSDMD） and gasdermin D-N-terminal domain （GSDMD-N） in lung tissue were detected. RESULTS Compared with the blank group， rats in the model group showed symptoms such as scratching their ears and noses and frequent sneezing； the lung tissue structure was severely damaged， and there was obvious inflammatory cell infiltration. The levels of inflammatory factors in BALF， as well as the level of MDA， TUNEL-apoptotic cell rate， the mRNA expression of NLRP3， and the protein expressions of NLRP3， cleaved caspase-1， caspase-1， GSDMD-N and GSDMD in lung tissue were significantly increased or up-regulated， while the level of SOD in lung tissue was significantly decreased （ P ＜0.05 or P ＜0.01）. Compared with the model group， the above symptoms and pathological damages of lung tissue in each drug group were significantly improved， and all quantitative indicators （except for the protein expressions of GSDMD in the STPC groups， as well as the level of SOD， and the protein expressions of cleaved caspase-1， caspase-1 and GSDMD-N in the STPC low-dose group） were significantly reversed （ P ＜0.05 or P ＜0.01）. CONCLUSIONS STPC can improve airway inflammation and lung tissue damage in rats with bronchial asthma， reduce the level of oxidative stress， and decrease the release of inflammatory factors such as IL-1β and IL-18. Its mechanism of action may be related to the inhibition of pyroptosis activation mediated by the NLRP3/caspase-1/GSDMD signaling pathway.

Objective:To establish a tumor tissue xenograft (PDX) model derived from liver cancer patients and explore the factors affecting tumorigenicity of liver cancer in the PDX model.Methods:The hepatocellular carcinoma tissues were inoculated subcutaneously in the axilla of NPG mice using the tissue block method to establish a PDX model. The demographic characteristics and related clinical examination data of 60 hepatocellular carcinoma patients were collected using the electronic medical record system and comprehensive medical information system of Beijing You'an Hospital, affiliated to Capital Medical University. The hepatocellular carcinoma samples of 24 cases were sequenced using the Oak Wing TM-808 gene detection reagent and high-throughput sequencing technology. SPSS 17.0 statistical software was used for statistical analysis, and the count data were analyzed using the χ2 test. Results:The tumorigenicity rate of PDX samples from 60 patients with liver cancer was 35% (21/60). The average tumorigenic duration in the PDX-P0 generation was 110.71±50.45 days. There were statistically significant differences ( P<0.05) corresponding to Edmondson grade ( χ2=5.910, P=0.015) and Ki67 expression ( χ2=4.615, P=0.032) among PDX with tumorigenicity and without tumorigenicity between the liver cancer samples. There was no statistically significant difference in gene mutation (TOP25) among PDX with tumorigenicity and without tumorigenicity between liver cancer samples. Conclusion:The factors affecting the tumorigenicity of liver cancer in PDX models are complex. The high pathological grade and strong Ki67 expression may be the key factors for the completion of liver cancer in PDX models.

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Liver cancer is one of the most common malignant tumors worldwide. Currently, the available treatment methods cannot fully control its recurrence and mortality rate. Establishing appropriate animal models for liver cancer is crucial for developing new treatment technologies and strategies. The patient-derived xenograft (PDX) model preserves the tumor's microenvironment and heterogeneity, which makes it advantageous for biological research, drug evaluation, personalized medicine, and other purposes. This article reviews the development, preparation techniques, application fields, and challenges of PDX models in liver cancer, providing insights for the research and exploration of PDX models in diagnostic and therapeutic strategies of liver cancer.
Liver Neoplasms/drug therapy* ; Animals ; Humans ; Xenograft Model Antitumor Assays/methods* ; Mice ; Disease Models, Animal

Objective:To establish a tumor tissue xenograft (PDX) model derived from liver cancer patients and explore the factors affecting tumorigenicity of liver cancer in the PDX model.Methods:The hepatocellular carcinoma tissues were inoculated subcutaneously in the axilla of NPG mice using the tissue block method to establish a PDX model. The demographic characteristics and related clinical examination data of 60 hepatocellular carcinoma patients were collected using the electronic medical record system and comprehensive medical information system of Beijing You'an Hospital, affiliated to Capital Medical University. The hepatocellular carcinoma samples of 24 cases were sequenced using the Oak Wing TM-808 gene detection reagent and high-throughput sequencing technology. SPSS 17.0 statistical software was used for statistical analysis, and the count data were analyzed using the χ2 test. Results:The tumorigenicity rate of PDX samples from 60 patients with liver cancer was 35% (21/60). The average tumorigenic duration in the PDX-P0 generation was 110.71±50.45 days. There were statistically significant differences ( P<0.05) corresponding to Edmondson grade ( χ2=5.910, P=0.015) and Ki67 expression ( χ2=4.615, P=0.032) among PDX with tumorigenicity and without tumorigenicity between the liver cancer samples. There was no statistically significant difference in gene mutation (TOP25) among PDX with tumorigenicity and without tumorigenicity between liver cancer samples. Conclusion:The factors affecting the tumorigenicity of liver cancer in PDX models are complex. The high pathological grade and strong Ki67 expression may be the key factors for the completion of liver cancer in PDX models.

Bronchial asthma （referred to as “asthma”） is a heterogeneous airway disease characterized by chronic airway inflammation and airway remodeling. Its pathogenesis is complex， the incidence is high and the disease is easy to repeat. Autophagy plays an important regulatory role in improving asthma symptoms. By regulating autophagy-related proteins and signaling pathways， the active components of traditional Chinese medicine （such as flavonoids， anthraquinones， terpenoids） and traditional Chinese medicine compounds （such as Wuhu decoction， Pingchuan granule， Sanzi yangqin decoction） can inhibit airway inflammatory response，reduce airway hyperresponsiveness，and alleviate airway remodeling，thus playing a role in the treatment of asthma. However， most of the current studies are basic studies，and the quality of evidence is not high．In the future，high-quality clinical and basic studies should be further carried out to fully demonstrate the scientific nature of traditional Chinese medicine in the treatment of asthma by regulating autophagy．

Objective To construct a recombinant eukaryotic expression vector of human tumor suppressor p53-binding protein 2(TP53BP2)and transfect human embryonic kidney Expi293F cells.High-purity recombinant human full-length TP53BP2 protein was obtained and its biological activity was identified.Methods The TP53BP2 gene sequence was queried on the UniProt website,and the Expi293F expression system was optimized.The TP53BP2 gene was connected to pcDNA3.1(+)-P2A-eGFP vector by homologous recombination,and identified by double enzyme digestion and sequencing.Transect pcDNA3.1(+)-P2A-eGFP-TP53BP2 plasmid into Expi293F cells of Polyethylenimine(PEI),observe the transfection efficiency with a fluorescence microscope,collected cells from the experiment group and control group.The expression level of TP53BP2 recombinant protein was detected by Western blot(WB).Protein was purified by His label purification kit and Superdex 20010/300 GL chromatographic column.Sodium dodecyl sulfate-polyacrylamide gel electrophoresis.The purified recombinant protein was identified by SDS-PAGE.Combining recombinant human full-length TP53BP2 protein with p65 protein was investigated for Co-immunoprecipitation(Co-IP)precipitation.Recombinant human full-length TP53BP2 protein was co-localized with p65 protein by Immunofluorescence(IF).The surface plasmon resonance(SPR)technique was used to detect the interaction between purified recombinant human full-length TP53BP2 protein and TP53BP2 antibody.Results The recombinant plasmid pcDNA3.1(+)-P2A-eGFP-TP53BP2 was successfully constructed by sequencing and double digestion.The fluorescence microscopy results showed that the transfection efficiency was about 60%.WB showed that the TP53BP2 protein was overexpressed in Expi293F cells,which proved that transfection was successful.SDS-PAGE results showed that the purity of the purified recombinant protein was above 90%,which proved that the purification was successful.Co-IP results showed that the TP53BP2 could interact with p65 protein.The results of IF showed that His tag protein,TP53BP2 protein,and p65 protein were co-located,indicating the interaction between the three proteins.SPR results showed that the purified TP53BP2 recombinant protein had good binding activity with the TP53BP2 antibody.These results all prove that the recombinant human full-length TP53BP2 protein has biological activity.Conclusion The eukaryotic expression vector of TP53BP2 gene was successfully constructed and the recombinant full-length human TP53BP2 protein with biological activity was successfully expressed in human embryonic kidney Expi293F cells.It lays a foundation for further study on the structure and function of TP53BP2.

In the context of non-alcoholic fatty liver disease (NAFLD), characterized by dysregulated lipid metabolism in hepatocytes, the quest for safe and effective therapeutics targeting lipid metabolism has gained paramount importance. Sanhuang Xiexin Tang (SXT) and Baihu Tang (BHT) have emerged as prominent candidates for treating metabolic disorders. SXT combined with BHT plus Cangzhu (SBC) has been used clinically for Weihuochisheng obese patients. This retrospective analysis focused on assessing the anti-obesity effects of SBC in Weihuochisheng obese patients. We observed significant reductions in body weight and hepatic lipid content among obese patients following SBC treatment. To gain further insights, we investigated the effects and underlying mechanisms of SBC in HFD-fed mice. The results demonstrated that SBC treatment mitigated body weight gain and hepatic lipid accumulation in HFD-fed mice. Pharmacological network analysis suggested that SBC may affect lipid metabolism, mitochondria, inflammation, and apoptosis-a hypothesis supported by the hepatic transcriptomic analysis in HFD-fed mice treated with SBC. Notably, SBC treatment was associated with enhanced hepatic mitochondrial biogenesis and the inhibition of the c-Jun N-terminal kinase (JNK)/nuclear factor-kappa B (NF-κB) and extracellular signal-regulated kinase (ERK)/NF-κB pathways. In conclusion, SBC treatment alleviates NAFLD in both obese patients and mouse models by improving lipid metabolism, potentially through enhancing mitochondrial biogenesis. These effects, in turn, ameliorate inflammation in hepatocytes.
Humans ; Mice ; Animals ; Non-alcoholic Fatty Liver Disease/metabolism* ; NF-kappa B/metabolism* ; Organelle Biogenesis ; Retrospective Studies ; Mice, Inbred C57BL ; Obesity/metabolism* ; Liver ; Inflammation/metabolism* ; Body Weight ; Lipid Metabolism ; Lipids ; Diet, High-Fat/adverse effects*

Dysregulation of mTORC1/mTORC2 pathway is observed in many cancers and mTORC1 inhibitors have been used clinically in many tumor types; however, the mechanism of mTORC2 in tumorigenesis is still obscure. Here, we mainly explored the potential role of mTORC2 in esophageal squamous cell carcinoma (ESCC) and its effects on the sensitivity of cells to mTOR inhibitors. We demonstrated that RICTOR, the key factor of mTORC2, and p-AKT (Ser473) were excessively activated in ESCC and their overexpression is related to lymph node metastasis and the tumor-node-metastasis (TNM) phase of ESCC patients. Furthermore, we found that mTORC1/ mTORC2 inhibitor PP242 exhibited more efficacious anti-proliferative effect on ESCC cells than mTORC1 inhibitor RAD001 due to RAD001-triggered feedback activation of AKT signal. Another, we demonstrated that down-regulating expression of RICTOR in ECa109 and EC9706 cells inhibited proliferation and migration as well as induced cell cycle arrest and apoptosis. Noteworthy, knocking-down stably RICTOR significantly suppresses RAD001-induced feedback activation of AKT/PRAS40 signaling, and enhances inhibition efficacy of PP242 on the phosphorylation of AKT and PRAS40, thus potentiates the antitumor effect of RAD001 and PP242 both and . Our findings highlight that selective targeting mTORC2 could be a promising therapeutic strategy for future treatment of ESCC.

OBJECTIVE: This study aims at investigating tympanogram in newborns who passed hearing screening using 226 and 1 000 Hz probe tones in order to interpret the test results correctly and find out its clinical value in audiological evaluation and diagnosis in this population. METHOD: Tympanogram was conducted using 226 and 1000 Hz probe tones in 206 newborns between 2 and 7 days of age (3.92 +/- 1.24) in both ears that passed the DPOAE screening and without any of the high risk register (HRR) factors associated with hearing loss according to the Joint Committee on Infant Hearing in 2007. RESULT: The tympanogram results tested in 408 ear were as following: the percentage of single-peaked, double-peaked, and none-peaked tympanograms using 226 Hz were 52.20% (213 ears), 47.55% (194 ears) and 0.25% (1 ear) respectively. The percentage of single-peaked and other morphological type tympanograms using 1000 Hz were 94.85%(387 ears) and 5.15% (21 ears) respectively. The parameters of 1000 Hz single-peaked tympanogram in this study were as following: the average tympanometric peak pressure was 33.24 +/- 44.37 dapa, the average peak compensated static acoustic admittance was 0.52 +/- 0.25 mmho, the average tympanometric width for right and left ears were 121.38 +/- 28.79 and 108.63 +/- 26.00 dapa respectively with a statistically significant difference between them (P < 0.01). The average volume of ear canal (Vec, using 226 Hz probe tone) at boys and girls were 0.44 +/- 0.10 and 0.43 +/- 0.08 ml respectively with a statistically significant difference between them (P < 0.05). CONCLUSION The morphology of tympanogram using a 226 Hz probe tone in newborns usually includes two main types: single-peaked and double-peaked, while it is primarily the single-peaked tympanogram while using a 1000 Hz probe tone. It is more appropriate to use a 1000 Hz probe tone than 226 Hz when testing newborns' tympanogram. The parameters obtained in this study using 1000 Hz and 226 Hz could be tried and applied to interpret clinical tympanogram test results and evaluate middle ear function. However, more studies with bigger sample size are necessary in this field.
Acoustic Impedance Tests ; Ear, Middle ; physiology ; Female ; Humans ; Infant, Newborn ; Male ; Neonatal Screening ; methods