ObjectiveTo investigate the therapeutic effects of Chaipo decoction on bronchial asthma in rats and its regulatory effects on the nucleotide-binding oligomerization domain-like receptor pyrin domain-containing protein 3 （NLRP3）/cysteinyl aspartate-specific protease-1 （Caspase-1）/Gasdermin D （GSDMD） pathway， aiming to elucidate its mechanism in ameliorating pyroptosis. MethodsSixty male Sprague-Dawley （SD） rats were randomly divided into six groups （n=10 per group）： normal control， asthma model， Chaipo decoction low-dose （5.0 g·kg^-1）， medium-dose （10.0 g·kg^-1）， high-dose （20.0 g·kg^-1）， and dexamethasone （1.0 mg·kg^-1）. The asthma model was established in all groups except the normal control group via ovalbumin （OVA） sensitization and challenge. Rats in the Chaipo decoction groups received intragastric administration of Chaipo decoction at the corresponding doses， while the dexamethasone group was treated with dexamethasone. The normal and model groups were administered equivalent volumes of saline. After 14 days of intervention， asthma symptom scores were assessed. Dynamic lung compliance （Cdyn）， lung resistance （RL）， and functional residual capacity （FRC） were measured using a small animal pulmonary function testing system. Lung tissue pathology was evaluated by hematoxylin-eosin （HE）， Masson's trichrome， and periodic acid-Schiff （PAS） staining. Levels of interleukin （IL）-6， IL-1β， and IL-18 in bronchoalveolar lavage fluid （BALF） were determined by enzyme-linked immunosorbent assay （ELISA）. Expression of NLRP3 and apoptosis-associated speck-like protein （ASC） in lung tissues was assessed by immunohistochemistry （IHC）. Protein levels of NLRP3， Caspase-1， GSDMD， and other pyroptosis-related proteins were measured by Western blot. ResultsCompared with the normal group， the model group exhibited significantly increased asthma symptom scores， inflammatory scores， collagen deposition， PAS scores， RL， FRC， levels of IL-6， IL-1β， and IL-18 in BALF， and expression levels of NLRP3， ASC， and other pyroptosis-related proteins in lung tissue （P0.01）， while Cdyn was significantly decreased （P0.01）. Compared with the model group， all doses of Chaipo decoction markedly improved asthma symptoms， with significantly reduced symptom scores （P0.05， P0.01）. Pulmonary function analysis showed that medium and high doses of Chaipo decoction significantly increased Cdyn （P0.05， P0.01） and decreased RL and FRC （P0.05， P0.01）. Histopathological evaluation indicated that high-dose Chaipo decoction significantly reduced inflammatory scores， collagen deposition， and goblet cell hyperplasia in lung tissue （P0.05， P0.01）. ELISA results showed that all doses of Chaipo decoction significantly decreased IL-6， IL-1β， and IL-18 levels in BALF （P0.05， P0.01）. IHC and Western blot analyses demonstrated that medium and high doses of Chaipo decoction markedly downregulated NLRP3， ASC， and other pyroptosis-related proteins in lung tissue （P0.05， P0.01）. ConclusionChaipo decoction effectively improves pulmonary function and pathological damage in asthmatic rats， potentially by inhibiting the NLRP3/Caspase-1/GSDMD pathway and reducing pyroptosis.

Immunotherapy has been widely used in cancer treatment in recent years and functions by stimulating the immune system to kill tumor cells. Radiation therapy (RT) uses radiation to induce DNA damage and kill tumor cells. However, this activates the body's immune system, promoting the release of tumor-related antigens from inactive dendritic cells, which stimulates the recurrence and metastasis of tumors in immune system tissues. The combination of RT and immunotherapy has been increasingly evaluated in recent years, with studies confirming the synergistic effect of the two antitumor therapies. Particularly, the combination of RT by dose adjustment with different immunotherapies has positive implications on antitumor immunity as well as disease prognosis compared with respective monotherapies. This review summarizes the current research status, progress, and prospects of RT combined with immunotherapy in cancer treatment. It additionally discusses the prevalent concerns regarding the dose, time window, and toxicity of this combination therapy.
Humans ; Neoplasms/radiotherapy* ; Immunotherapy/methods* ; Combined Modality Therapy ; Radiotherapy/methods*

Sheep pox is widespread worldwide and is the most severe animal pox virus infection. This study aimed to identify the key microRNAs (miRNAs) differentially expressed in the exosomes of sheep poxvirus-infected cells and their target genes and related pathways and provide a theoretical basis for an in-depth understanding of the molecular mechanisms of sheep poxvirus-infected cells. In this study, the differentially expressed miRNAs were verified by quantitative polymerase chain reaction (qPCR), and the target genes of miRNAs were predicted and analyzed by bioinformatics. The qPCR results showed that the expression trends of oar-miR-21, oar-miR-10b, oar-let-7f, oar-let-7b, and oar-miR-221 were consistent with the sequencing results. The Gene Ontology and Kyoto Encyclopedia of Genes and Genomes results showed that differentially expressed miRNAs were mainly involved in the immune system processes of the Arf6 downstream pathway. The target genes Reactome pathways were mainly enriched in the RAC1 GTPase cycle, CDC42 GTPase cycle, RHO GTPase cycle, RHOV GTPase cycle, and post-transcriptional silencing of small RNAs. The transcription factors SP4, NKX6-1, MEF2A, SP1, EGR1, and POU2F1 that may be connected to sheep pox virus (SPPV)-infected cells were discovered by transcription factor annotation screening. In conclusion, this study screened for differentially expressed miRNAs in SPPV-infected cells and performed a series of bioinformatic analyses of their target genes to provide a theoretical basis for the molecular mechanism of sheep pox virus infections of cells. The data can be used as basic information in future studies on the defense mechanisms against poxvirus infections.

Sheep pox is widespread worldwide and is the most severe animal pox virus infection. This study aimed to identify the key microRNAs (miRNAs) differentially expressed in the exosomes of sheep poxvirus-infected cells and their target genes and related pathways and provide a theoretical basis for an in-depth understanding of the molecular mechanisms of sheep poxvirus-infected cells. In this study, the differentially expressed miRNAs were verified by quantitative polymerase chain reaction (qPCR), and the target genes of miRNAs were predicted and analyzed by bioinformatics. The qPCR results showed that the expression trends of oar-miR-21, oar-miR-10b, oar-let-7f, oar-let-7b, and oar-miR-221 were consistent with the sequencing results. The Gene Ontology and Kyoto Encyclopedia of Genes and Genomes results showed that differentially expressed miRNAs were mainly involved in the immune system processes of the Arf6 downstream pathway. The target genes Reactome pathways were mainly enriched in the RAC1 GTPase cycle, CDC42 GTPase cycle, RHO GTPase cycle, RHOV GTPase cycle, and post-transcriptional silencing of small RNAs. The transcription factors SP4, NKX6-1, MEF2A, SP1, EGR1, and POU2F1 that may be connected to sheep pox virus (SPPV)-infected cells were discovered by transcription factor annotation screening. In conclusion, this study screened for differentially expressed miRNAs in SPPV-infected cells and performed a series of bioinformatic analyses of their target genes to provide a theoretical basis for the molecular mechanism of sheep pox virus infections of cells. The data can be used as basic information in future studies on the defense mechanisms against poxvirus infections.

Sheep pox is widespread worldwide and is the most severe animal pox virus infection. This study aimed to identify the key microRNAs (miRNAs) differentially expressed in the exosomes of sheep poxvirus-infected cells and their target genes and related pathways and provide a theoretical basis for an in-depth understanding of the molecular mechanisms of sheep poxvirus-infected cells. In this study, the differentially expressed miRNAs were verified by quantitative polymerase chain reaction (qPCR), and the target genes of miRNAs were predicted and analyzed by bioinformatics. The qPCR results showed that the expression trends of oar-miR-21, oar-miR-10b, oar-let-7f, oar-let-7b, and oar-miR-221 were consistent with the sequencing results. The Gene Ontology and Kyoto Encyclopedia of Genes and Genomes results showed that differentially expressed miRNAs were mainly involved in the immune system processes of the Arf6 downstream pathway. The target genes Reactome pathways were mainly enriched in the RAC1 GTPase cycle, CDC42 GTPase cycle, RHO GTPase cycle, RHOV GTPase cycle, and post-transcriptional silencing of small RNAs. The transcription factors SP4, NKX6-1, MEF2A, SP1, EGR1, and POU2F1 that may be connected to sheep pox virus (SPPV)-infected cells were discovered by transcription factor annotation screening. In conclusion, this study screened for differentially expressed miRNAs in SPPV-infected cells and performed a series of bioinformatic analyses of their target genes to provide a theoretical basis for the molecular mechanism of sheep pox virus infections of cells. The data can be used as basic information in future studies on the defense mechanisms against poxvirus infections.

Sheep pox is widespread worldwide and is the most severe animal pox virus infection. This study aimed to identify the key microRNAs (miRNAs) differentially expressed in the exosomes of sheep poxvirus-infected cells and their target genes and related pathways and provide a theoretical basis for an in-depth understanding of the molecular mechanisms of sheep poxvirus-infected cells. In this study, the differentially expressed miRNAs were verified by quantitative polymerase chain reaction (qPCR), and the target genes of miRNAs were predicted and analyzed by bioinformatics. The qPCR results showed that the expression trends of oar-miR-21, oar-miR-10b, oar-let-7f, oar-let-7b, and oar-miR-221 were consistent with the sequencing results. The Gene Ontology and Kyoto Encyclopedia of Genes and Genomes results showed that differentially expressed miRNAs were mainly involved in the immune system processes of the Arf6 downstream pathway. The target genes Reactome pathways were mainly enriched in the RAC1 GTPase cycle, CDC42 GTPase cycle, RHO GTPase cycle, RHOV GTPase cycle, and post-transcriptional silencing of small RNAs. The transcription factors SP4, NKX6-1, MEF2A, SP1, EGR1, and POU2F1 that may be connected to sheep pox virus (SPPV)-infected cells were discovered by transcription factor annotation screening. In conclusion, this study screened for differentially expressed miRNAs in SPPV-infected cells and performed a series of bioinformatic analyses of their target genes to provide a theoretical basis for the molecular mechanism of sheep pox virus infections of cells. The data can be used as basic information in future studies on the defense mechanisms against poxvirus infections.

Sheep pox is widespread worldwide and is the most severe animal pox virus infection. This study aimed to identify the key microRNAs (miRNAs) differentially expressed in the exosomes of sheep poxvirus-infected cells and their target genes and related pathways and provide a theoretical basis for an in-depth understanding of the molecular mechanisms of sheep poxvirus-infected cells. In this study, the differentially expressed miRNAs were verified by quantitative polymerase chain reaction (qPCR), and the target genes of miRNAs were predicted and analyzed by bioinformatics. The qPCR results showed that the expression trends of oar-miR-21, oar-miR-10b, oar-let-7f, oar-let-7b, and oar-miR-221 were consistent with the sequencing results. The Gene Ontology and Kyoto Encyclopedia of Genes and Genomes results showed that differentially expressed miRNAs were mainly involved in the immune system processes of the Arf6 downstream pathway. The target genes Reactome pathways were mainly enriched in the RAC1 GTPase cycle, CDC42 GTPase cycle, RHO GTPase cycle, RHOV GTPase cycle, and post-transcriptional silencing of small RNAs. The transcription factors SP4, NKX6-1, MEF2A, SP1, EGR1, and POU2F1 that may be connected to sheep pox virus (SPPV)-infected cells were discovered by transcription factor annotation screening. In conclusion, this study screened for differentially expressed miRNAs in SPPV-infected cells and performed a series of bioinformatic analyses of their target genes to provide a theoretical basis for the molecular mechanism of sheep pox virus infections of cells. The data can be used as basic information in future studies on the defense mechanisms against poxvirus infections.

Objective To study the value of postmortem imaging on the diagnosis of intestinal perforation.Method Postmortem imaging(PMCT and PMCTA)data of 2 intestinal perforation deaths(and 4 controlled cases)were reviewed retrospectively.Diagnosing capacities of intestinal perforation by postmortem imaging method were further investigated.Results PMCT is sensitive in detecting the free air and liquid induced by intestinal perforation.PMCT can sometimes detect the gravity-dependent purulent secretions in the abdominopelvic cavity.PMCTA can visualize the extravasation of contrast agent from the perforation,which can be used to locate the accurate perforation region.Conclusion Postmortem imaging method(PMCT and PMCTA)is an important tool for the diagnosis of intestinal perforation,which can not only be used as a forensic diagnosis method,but is also useful to locate the perforation site before an forensic autopsy.

Objective To understand the current practice status of central venous access device(CVAD)maintenance among intensive care unit(ICU)nurses in secondary and above medical institutions in Shandong province,and to provide a basis for further implementation of effective measures to reduce the incidence of central catheter-related bloodstream infections.Methods The CVAD maintenance practice questionnaire was compiled based on domestic and international evidence related to CVAD maintenance,and a survey was conducted in October 2022 to investigate the status of ICU nurses' CVAD maintenance practice in secondary and above medical institutions in Shandong Province.Results There were 1 492 nurses participated in the survey and 1 461 valid questionnaires were recovered,with a valid recovery rate of 97.92％.The type of CVAD used by the nurses was mainly central venous catheters[92.3％(1349/1461)],and the item with the best assessment at each operation was patency of the catheter[81.1％(1185/1461)],and the worst was the patient's feeling[40.7％(594/1 461)].When assessing catheter patency,[59.8％(873/1 461)]of nurses drew back blood into the catheter.In the use of infusion connectors,three-way connectors[76.0％(1 110/1 461)]and heparin caps[62.3％(910/1 461)]were most frequently used.When sterilizing needleless connectors,most nurses could follow the correct range of disinfection,but the time of disinfection needed to be extended,and the most used items for disinfection were povidone-iodine cotton balls/swabs[44.3％(647/1 461)].The timing of changing infusion connectors needs to be standardized.Most nurses would choose saline for catheter flushing,and the number of nurses choosing saline versus heparinized saline when locking the catheter was about 50％.Most nurses can use correct size syringes and follow standardized techniques for flushing and locking.When performing CVAD maintenance,84.7％(1 237/1 461)of nurses chose a specialized care package kit.The most used skin antiseptic was povidone-iodine[63.7％(931/1 461)].Most nurses could follow the standardized range of skin disinfection,but awareness of drying needs to be improved.Dressings covering puncture points were most frequently transparent[99.7％(1 457/1 461)]and gauze[94.7％(1 383/1 461)],and the frequency of gauze dressing changes needs to be standardized.Hand hygiene and aseptic awareness of nurses during CVAD maintenance was good,but hand hygiene and the timing of wearing sterile gloves need to be standardized.Conclusions ICU nurses' CVAD maintenance practices were generally in line with the latest evidence-based recommendations,but assessment,use of maintenance-related items,and hand hygiene and aseptic technique need to be further standardized.It is recommended that nursing administrators enhance ICU nursing human resource allocation as much as possible and form a central line associated bloodstream infection(CLABSI)prevention and control management system to gradually reduce the morbidity of CLABSI within the ICU.

OBJECTIVE: To explore the correlation of mitochondrial DNA (mtDNA) variants and coronary heart disease (CHD) in a Chinese pedigree and the possible molecular mechanisms. METHODS: A Chinese pedigree featuring matrilineal inheritance of CHD who visited Hangzhou First People's Hospital in May 2022 was selected as the study subject. Clinical data of the proband and her affected relatives was collected. By sequencing the mtDNA of the proband and her pedigree members, candidate variants were identified through comparison with wild type mitochondrial genes. Conservative analysis among various species was conducted, and bioinformatics software was used to predict the impact of variants on the secondary structure of tRNA. Real-time PCR was carried out to determine the copy number of mtDNA, and a transmitochondrial cell line was established for analyzing the mitochondrial functions, including membrane potential and ATP level. RESULTS: This pedigree had contained thirty-two members from four generations. Among ten maternal members, four had CHD, which yielded a penetrance rate of 40%. Sequence analysis of proband and her matrilineal relatives revealed the presence of a novel m.4420A>T variant and a m.10463T>C variant, both of which were highly conserved among various species. Structurally, the m.4420A>T variant had occurred at position 22 in the D-arm of tRNAMet, which disrupted the 13T-22A base-pairing, while the m.10463T>C variant was located at position 67 in the acceptor arm of tRNAArg, a position critical for steady-state level of the tRNA. Functional analysis revealed that patients with the m.4420A>T and m.10463T>C variants exhibited much fewer copy number of mtDNA and lower mitochondrial membrane potential (MMP) and ATP contents (P < 0.05), which were decreased by approximately 50.47%, 39.6% and 47.4%, respectively. CONCLUSION Mitochondrial tRNAMet 4420A>T and tRNAArg 10463T>C variants may underlay the maternally transmitted CHD in this pedigree, which had shown variation in mtDNA homogeneity, age of onset, clinical phenotype and other differences, suggesting that nuclear genes, environmental factors and mitochondrial genetic background have certain influence on the pathogenesis of CHD.
Humans ; Female ; Mutation ; Pedigree ; RNA, Transfer, Met ; East Asian People ; RNA, Transfer, Arg ; DNA, Mitochondrial/genetics* ; Coronary Disease/genetics* ; Adenosine Triphosphate