OBJECTIVE To identify the quality markers （Q-Markers） of Hyssopus cuspidatus against airway remodeling in bronchial asthma （referred to as “asthma”）， an d to provide a reference for the quality control research of H. cuspidatus based on pharmacodynamic activity. METHODS Potential active components and action targets of H. cuspidatus were screened by network pharmacology method. Using human airway smooth muscle cells （HASMCs） as objects， airway remodeling cell model was induced by platelet-derived growth factor-BB （PDGF-BB）； validation test was then performed for anti-asthmatic effects of H. cuspidatus and the potential active components. HPLC method was employed to establish the fingerprints of 14 batches of H. cuspidatus samples， and chemometric analysis was also conducted. Combined with the results of pharmacodynamic experiments and fingerprint analysis， the Q-Markers of H. cuspidatus against airway remodeling in asthma were determined. RESULTS&CONCLUSIONS Network pharmacology analysis showed that the potential active components of H. cuspidatus against asthma might be flavonoids and phenolic acids such as luteolin， quercetin and rosmarinic acid， and the core anti-asthmatic targets were interleukin-6， mitogen-activated protein kinase， etc. In vitro experimental results confirmed that 25， 50， 100 μg/mL of H. cuspidatus ， as well as neochlorogenic acid （80 μmol/L）， acacetin （80 μmol/L）， salvianolic acid B （40 μmol/L） and quercetin-3- O - β -D-glucuronide （80 μmol/L）， significantly reduced the cell viability induced by PDGF-BB， inhibited cell proliferation， migration， and the phosphorylation level of extracellular signal-regulated protein kinase 1/2， decreased the levels of interleukin-6， tumor necrosis factor-α and reactive oxygen species， and generally arrested cells in the G 0 /G 1 phase （ P ＜0.05）. Fingerprint analysis showed that there were 27 common peaks in the fingerprints of the 14 batches of H. cuspidatus samples， with 15 compounds （including luteolin） identified， and the similarities of fingerprints were all greater than 0.8. The 14 batches of samples could be divided into three categories： S1-S7 as one category， S8-S13 as one category， and S14 as one category. The variable importance in the projection values of rosmarinic acid， chlorogenic acid， caffeic acid， salvigenin， luteolin， ferulic acid， quercetin-3- O - β -D-glucuronide， and the components corresponding to peaks 5 and 8 were greater than 1， indicating they were potential differential markers affecting quality. Integrating network pharmacology， in vitro experimental validation， and chemometric analysis， rosmarinic acid， neochlorogenic acid， caffeic acid， salvigenin， luteolin， ferulic acid， quercetin-3- O - β -D-glucuronide， acacetin， salvianolic acid B and chlorogenic acid may be the Q-Markers of H. cuspidatus against asthma.

Objective To analyze the epidemiological characteristics and risk factors of an outbreak of influenza A H1N1 in a specialized psychiatric hospital in Shantou City,Guangdong Province,provide scientific basis for the pre-vention and control of respiratory infectious diseases in psychiatric health institutions.Methods Data of infection cases in this hospital in May 1-27,2024 were collected with on-site epidemiological investigation method,and were analyzed with descriptive epidemiological methods.The specimens of the cases were performed nucleic acid testing by reverse transcription polymerase chain reaction(RT-PCR)method.Results A total of 43 influenza-like cases in this outbreak have been reported,with an incidence of 16.67％,including 42 hospitalized patients and 1 healthcare worker.Among the 42 hospitalized patients,there were 41 males,with an incidence of 35.04％and 1 female with an incidence of 2.22％,there was a statistically significant difference in incidence between hospitalized patients of different genders(x2=18.23,P＜0.001).The epidemic curve shows that after the first case appeared on May 8,2024,the number of cases increased significantly from May 13,and reached its peak on May 17(n=17).31 pa-tients' throat swab specimens were collected,out of which 29(93.55％)were positive for influenza A H1N1 virus nucleic acid and 2(6.45％)were negative.Conclusion This epidemic is an outbreak of influenza A H1N1 in a psy-chiatric health institution,the epidemic curve shows a point source human-to-human transmission mode.Failure to effectively identify and isolate cases in the early stage can lead to the spread of the epidemic across floors and wards.It is necessary to regularly organize hospitalized patients and healthcare workers to receive influenza vaccines,strict-ly implement the health monitoring system,strengthen the control of external personnel,and enhance the early de-tection and emergency response capabilities for infectious disease outbreaks.

Objective To analyze the epidemiological characteristics and risk factors of an outbreak of influenza A H1N1 in a specialized psychiatric hospital in Shantou City,Guangdong Province,provide scientific basis for the pre-vention and control of respiratory infectious diseases in psychiatric health institutions.Methods Data of infection cases in this hospital in May 1-27,2024 were collected with on-site epidemiological investigation method,and were analyzed with descriptive epidemiological methods.The specimens of the cases were performed nucleic acid testing by reverse transcription polymerase chain reaction(RT-PCR)method.Results A total of 43 influenza-like cases in this outbreak have been reported,with an incidence of 16.67％,including 42 hospitalized patients and 1 healthcare worker.Among the 42 hospitalized patients,there were 41 males,with an incidence of 35.04％and 1 female with an incidence of 2.22％,there was a statistically significant difference in incidence between hospitalized patients of different genders(x2=18.23,P＜0.001).The epidemic curve shows that after the first case appeared on May 8,2024,the number of cases increased significantly from May 13,and reached its peak on May 17(n=17).31 pa-tients' throat swab specimens were collected,out of which 29(93.55％)were positive for influenza A H1N1 virus nucleic acid and 2(6.45％)were negative.Conclusion This epidemic is an outbreak of influenza A H1N1 in a psy-chiatric health institution,the epidemic curve shows a point source human-to-human transmission mode.Failure to effectively identify and isolate cases in the early stage can lead to the spread of the epidemic across floors and wards.It is necessary to regularly organize hospitalized patients and healthcare workers to receive influenza vaccines,strict-ly implement the health monitoring system,strengthen the control of external personnel,and enhance the early de-tection and emergency response capabilities for infectious disease outbreaks.

Objective:Glucorticoid therapy has the potential to mitigate immunogical effect of naxitamab. Ketamine is an anesthetic medica-tion and cause weak or shallow breathing. This article is to analyze the effect of modified conditioning regimen with substitution re-mifentanil for ketamine and without glucorticoid therapy on adverse events associated with naxitamab. Methods:Clinical data with naxit-amab infusion under modified conditioning regimen in Sun Yat-sen University Cancer Center between June 2023 and June 2024 were re-trieved to analyze adverse events and risk factors. Results:Overall,seventeen patients underwent 201 infusions. The most frequent adverse events were as follows:neurological pain (all grades) 93.0％,hypertension 55.7％,hypotension 34.8％,respectively. Bronchospasm and hyp-oxia were seen in 3.0％ and 10.9％ infusions,respectively. Fever occurred less frequently in the second cycle of infusion. No patients suspen-ded infusion due to severe adverse event. Conclusions:The infusion of naxitamab is tolerable under the modified conditioning regimen and adverse event is less than expected and controllable.

Objective:Glucorticoid therapy has the potential to mitigate immunogical effect of naxitamab. Ketamine is an anesthetic medica-tion and cause weak or shallow breathing. This article is to analyze the effect of modified conditioning regimen with substitution re-mifentanil for ketamine and without glucorticoid therapy on adverse events associated with naxitamab. Methods:Clinical data with naxit-amab infusion under modified conditioning regimen in Sun Yat-sen University Cancer Center between June 2023 and June 2024 were re-trieved to analyze adverse events and risk factors. Results:Overall,seventeen patients underwent 201 infusions. The most frequent adverse events were as follows:neurological pain (all grades) 93.0％,hypertension 55.7％,hypotension 34.8％,respectively. Bronchospasm and hyp-oxia were seen in 3.0％ and 10.9％ infusions,respectively. Fever occurred less frequently in the second cycle of infusion. No patients suspen-ded infusion due to severe adverse event. Conclusions:The infusion of naxitamab is tolerable under the modified conditioning regimen and adverse event is less than expected and controllable.

Postzygotic mutations are acquired in normal tissues throughout an individual's lifetime and hold clues for identifying mutagenic factors.Here,we investigated postzygotic mutation spectra of healthy individuals using optimized ultra-deep exome sequencing of the time-series samples from the same volunteer as well as the samples from different individuals.In blood,sperm,and muscle cells,we resolved three common types of mutational signatures.Signatures A and B represent clock-like mutational processes,and the polymorphisms of epigenetic regulation genes influence the pro-portion of signature B in mutation profiles.Notably,signature C,characterized by C＞T transitions at GpCpN sites,tends to be a feature of diverse normal tissues.Mutations of this type are likely to occur early during embryonic development,supported by their relatively high allelic frequencies,presence in multiple tissues,and decrease in occurrence with age.Almost none of the public datasets for tumors feature this signature,except for 19.6％of samples of clear cell renal cell carcinoma with increased activation of the hypoxia-inducible factor 1(HIF-1)signaling pathway.Moreover,the accumulation of signature C in the mutation profile was accelerated in a human embryonic stem cell line with drug-induced activation of HIF-1α.Thus,embryonic hypoxia may explain this novel signature across multiple normal tissues.Our study suggests that hypoxic condition in an early stage of embryonic development is a crucial factor inducing C＞T transitions at GpCpN sites;and indi-viduals'genetic background may also influence their postzygotic mutation profiles.

The drug poisoning is the most common cause of children′s accident.The percentage is increasing every year. Analgesics,non-steroidal anti-inflammatory drugs and antihistamines are the most commonly ingested drugs in children.The principles of management of drug poisoning are:(1)resuscitation and initial stabilization; (2)diagnosis of type of poision.According to recent studies,gastric lavage should not routinely be used in all poisoning cases,instead the use of activated carbon is recommended.For severe or special cases advanced life support technologies such as mechanical ventilation,blood purification,extracorpo-real membrane oxygenation should be considered.

Maintenance of cell junctions plays a crucial role in the regulation of cellular functions including cell proliferation, permeability, and cell death. Disruption of cell junctions is implicated in a variety of human disorders, such as inflammatory diseases and cancers. Understanding molecular regulation of cell junctions is important for development of therapeutic strategies for intervention of human diseases. Ubiquitination is an important type of post-translational modification that primarily regulates endogenous protein stability, receptor internalization, enzyme activity, and protein-protein interactions. Ubiquitination is tightly regulated by ubiquitin E3 ligases and can be reversed by deubiquitinating enzymes. Recent studies have been focusing on investigating the effect of protein stability in the regulation of cell-cell junctions. Ubiquitination and degradation of cadherins, claudins, and their interacting proteins are implicated in epithelial and endothelial barrier disruption. Recent studies have revealed that ubiquitination is involved in regulation of Rho GTPases' biological activities. Taken together these studies, ubiquitination plays a critical role in modulating cell junctions and motility. In this review, we will discuss the effects of ubiquitination and deubiquitination on protein stability and expression of key proteins in the cell-cell junctions, including junction proteins, their interacting proteins, and small Rho GTPases. We provide an overview of protein stability in modulation of epithelial and endothelial barrier integrity and introduce potential future search directions to better understand the effects of ubiquitination on human disorders caused by dysfunction of cell junctions.
Animals ; Humans ; Inflammation ; metabolism ; pathology ; Intercellular Junctions ; metabolism ; Neoplasms ; metabolism ; pathology ; Protein Stability ; Ubiquitin-Protein Ligases ; metabolism ; Ubiquitination