ObjectiveThe proteome of biological evidence contains rich genetic information, namely single amino acid polymorphisms (SAPs) in protein sequences. However, due to the lack of efficient and convenient analysis tools, the application of SAP in public security still faces many challenges. This paper aims to meet the application requirements of SAP analysis for forensic biological evidence’s proteome data. MethodsThe software is divided into three modules. First, based on a built-in database of common non-synonymous single nucleotide polymorphisms (nsSNPs) and SAPs in East Asian populations, the software integrates and annotates newly identified exonic nsSNPs as SAPs, thereby constructing a customized SAP protein sequence database. It then utilizes a pre-installed search engine—either pFind or MaxQuant—to perform analysis and output SAP typing results, identifying both reference and variant types, along with their corresponding imputed nsSNPs. Finally, SAPTyper compares the proteome-based typing results with the individual’s exome-derived nsSNP profile and outputs the comparison report. ResultsSAPTyper accepts proteomic DDA mass spectrometry raw data (DDA acquisition mode) and exome sequencing results of nsSNPs as input and outputs the report of SAPs result. The pFind and Maxquant search engines were used to test the proteome data of 2 hair shafts of2 individuals, and both obtained SAP results. It was found that the results of the Maxquant search engine were slightly less than those of pFind. This result shows that SAPTyper can achieve SAP fingding function. Moreover, the pFind search engine was used to test the proteome data of 3 hair shafts from 1 European person and 1 African person in the literature. Among the sites fully matched by the literature method, sites detected by SAPTyper are also included; for semi-matching sites, that is, nsSNPs are heterozygous, both literature method and SAPTyper method had the risk of missing detection for one type of the allele. Comparing the analysis results of SAPTyper with the SAP test results reported in the literature, it was found that some imputed nsSNP sites identified by the literature method but not detected by SAPTyper had a MAF of less than 0.1% in East Asian populations, and therefore they were not included in the common nsSNP database of East Asian populations constructed by this software. Since the database construction of this software is based on the genetic variation information of East Asian populations, it is currently unable to effectively identify representative unique common variation sites in European or African populations, but it can still identify SAP sites shared by these populations and East Asian populations. ConclusionAn automated SAP analysis algorithm was developed for East Asian populations, and the software named SAPTyper was developed. This software provides a convenient and efficient analysis tool for the research and application of forensic proteomic SAP and has important application prospects in individual identification and phenotypic inference based on SAP.

OBJECTIVE: Gastric cancer (GC) is one of the most common malignancies seen in clinic and requires novel treatment options. Morin is a natural flavonoid extracted from the flower stalk of a highly valuable medicinal plant Prunella vulgaris L., which exhibits an anti-cancer effect in multiple types of tumors. However, the therapeutic effect and underlying mechanism of morin in treating GC remains elusive. The study aims to explore the therapeutic effect and underlying molecular mechanisms of morin in GC. METHODS: For in vitro experiments, the proliferation inhibition of morin was measured by cell counting kit-8 assay and colony formation assay in human GC cell line MKN45, human gastric adenocarcinoma cell line AGS, and human gastric epithelial cell line GES-1; for apoptosis analysis, microscopic photography, Western blotting, ubiquitination analysis, quantitative polymerase chain reaction analysis, flow cytometry, and RNA interference technology were employed. For in vivo studies, immunohistochemistry, biomedical analysis, and Western blotting were used to assess the efficacy and safety of morin in a xenograft mouse model of GC. RESULTS: Morin significantly inhibited the proliferation of GC cells MKN45 and AGS in a dose- and time-dependent manner, but did not inhibit human gastric epithelial cells GES-1. Only the caspase inhibitor Z-VAD-FMK was able to significantly reverse the inhibition of proliferation by morin in both GC cells, suggesting that apoptosis was the main type of cell death during the treatment. Morin induced intrinsic apoptosis in a dose-dependent manner in GC cells, which mainly relied on B cell leukemia/lymphoma 2 (BCL-2) associated agonist of cell death (BAD) but not phorbol-12-myristate-13-acetate-induced protein 1. The upregulation of BAD by morin was due to blocking the ubiquitination degradation of BAD, rather than the transcription regulation and the phosphorylation of BAD. Furthermore, the combination of morin and BCL-2 inhibitor navitoclax (also known as ABT-737) produced a synergistic inhibitory effect in GC cells through amplifying apoptotic signals. In addition, morin treatment significantly suppressed the growth of GC in vivo by upregulating BAD and the subsequent activation of its downstream apoptosis pathway. CONCLUSION Morin suppressed GC by inducing apoptosis, which was mainly due to blocking the ubiquitination-based degradation of the pro-apoptotic protein BAD. The combination of morin and the BCL-2 inhibitor ABT-737 synergistically amplified apoptotic signals in GC cells, which may overcome the drug resistance of the BCL-2 inhibitor. These findings indicated that morin was a potent and promising agent for GC treatment. Please cite this article as: Wang Y, Sun XY, Ma FQ, Ren MM, Zhao RH, Qin MM, Zhu XH, Xu Y, Cao ND, Chen YY, Dong TG, Pan YF, Zhao AG. Morin inhibits ubiquitination degradation of BCL-2 associated agonist of cell death and synergizes with BCL-2 inhibitor in gastric cancer cells. J Integr Med. 2025; 23(3): 320-332.
Humans ; Flavonoids/therapeutic use* ; Stomach Neoplasms/pathology* ; Animals ; Proto-Oncogene Proteins c-bcl-2/metabolism* ; Cell Line, Tumor ; Apoptosis/drug effects* ; Cell Proliferation/drug effects* ; Ubiquitination/drug effects* ; Mice ; Drug Synergism ; Mice, Inbred BALB C ; Mice, Nude ; Xenograft Model Antitumor Assays ; Flavones

General anesthesia is widely used in clinical practice,whereas the exact mechanism behind the general anesthetic-induced reversible loss of consciousness remains unclear.Recent studies have revealed a close relationship between the dopaminergic system and general anesthetic-induced loss of consciousness.This system,encompassing dopamine neurons,dopamine receptors,and related neural pathways,regulates functions such as movement,memory,arousal,and cognition.The dopaminergic neurons in the ventral periaqueductal gray and ventral tegmental area,along with D1 receptors,have been shown to facilitate emergence from anesthesia.However,the role of D2 receptors remains controversial.This review summarizes recent advancements in the role of the dopaminergic system in general anesthesia and the underlying mechanism,with the aim of clarifying the mechanism of general anesthesia and providing a theoretical basis for preventing delayed emergence from anesthesia.
Humans ; Anesthesia, General ; Brain/metabolism* ; Dopaminergic Neurons/physiology* ; Dopamine/physiology* ; Animals

Objective To explore the efficacy and safety of recombinant human anti-severe acute respiratory syn-drome coronavirus 2(anti-SARS-CoV-2)monoclonal antibody injection(F61 injection)in the treatment of patients with coronavirus disease 2019(COVID-19)combined with renal damage.Methods Patients with COVID-19 and renal damage who visited the PLA General Hospital from January to February 2023 were selected.Subjects were randomly divided into two groups.Control group was treated with conventional anti-COVID-19 therapy,while trial group was treated with conventional anti-COVID-19 therapy combined with F61 injection.A 15-day follow-up was conducted after drug administration.Clinical symptoms,laboratory tests,electrocardiogram,and chest CT of pa-tients were performed to analyze the efficacy and safety of F61 injection.Results Twelve subjects(7 in trial group and 5 in control group)were included in study.Neither group had any clinical progression or death cases.The ave-rage time for negative conversion of nucleic acid of SARS-CoV-2 in control group and trial group were 3.2 days and 1.57 days(P=0.046),respectively.The scores of COVID-19 related target symptom in the trial group on the 3rd and 5th day after medication were both lower than those of the control group(both P＜0.05).According to the clinical staging and World Health Organization 10-point graded disease progression scale,both groups of subjects improved but didn't show statistical differences(P＞0.05).For safety,trial group didn't present any infusion-re-lated adverse event.Subjects in both groups demonstrated varying degrees of elevated blood glucose,elevated urine glucose,elevated urobilinogen,positive urine casts,and cardiac arrhythmia,but the differences were not statistica-lly significant(all P＞0.05).Conclusion F61 injection has initially demonstrated safety and clinical benefit in trea-ting patients with COVID-19 combined with renal damage.As the domestically produced drug,it has good clinical accessibility and may provide more options for clinical practice.

BACKGROUND: In China, lung cancer remains the cancer with the highest incidence and mortality rate. Among early-stage lung adenocarcinomas (LUAD), the micropapillary (MPP) component is prevalent and typically exhibits high aggressiveness, significantly correlating with early metastasis, lymphatic infiltration, and reduced five-year survival rates. Therefore, the study is to explore the similarities and differences between MPP and non-micropapillary (non-MPP) components in malignant pulmonary nodules characterized by GGOs in early-stage LUAD, identify unique mutational features of the MPP component and analyze the relationship between the ZNF469 gene, a member of the zinc-finger protein family, and the prognosis of early-stage LUAD, as well as its correlation with immune infiltration. METHODS: A total of 31 malignant pulmonary nodules of LUAD were collected and dissected into paired MPP and non-MPP components using microdissection. Whole-exome sequencing (WES) was performed on the components of early-stage malignant pulmonary nodules. Mutational signatures analysis was conducted using R packages such as maftools, Nonnegative Matrix Factorization (NMF), and Sigminer to unveil the genomic mutational characteristics unique to MPP components in invasive LUAD compared to other tumor tissues. Furthermore, we explored the expression of the ZNF469 gene in LUAD using The Cancer Genome Atlas (TCGA) database to investigate its potential association with the prognosis. We also investigated gene interaction networks and signaling pathways related to ZNF469 in LUAD using the GeneMANIA database and conducted Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. Lastly, we analyzed the correlation between ZNF469 gene expression and levels of immune cell infiltration in LUAD using the TIMER and TISIDB databases. RESULTS: MPP components exhibited a higher number of genomic variations, particularly the 13th COSMIC (Catalogue of Somatic Mutations in Cancer) mutational signature characterized by the activity of the cytidine deaminase APOBEC family, which was unique to MPP components compared to non-MPP components in tumor tissues. This suggests the potential involvement of APOBEC in the progression of MPP components in early-stage LUAD. Additionally, MPP samples with high similarity to APOBEC signature displayed a higher tumor mutational burden (TMB), indicating that these patients may be more likely to benefit from immunotherapy. The expression of ZNF469 was significantly upregulated in LUAD compared to normal tissue, and was associated with poor prognosis in LUAD patients (P<0.05). Gene interaction network analysis and GO/KEGG enrichment analysis revealed that COL6A1, COL1A1, COL1A2, TGFB2, MMP2, COL8A2 and C2CD4C interacted with ZNF469 and were mainly involved in encoding collagen proteins and participating in the constitution of extracellular matrix. ZNF469 expression was positively correlated with immune cell infiltration in LUAD (P<0.05). CONCLUSIONS The study has unveiled distinctive mutational signatures in the MPP components of early-stage invasive LUAD in the Asian population. Furthermore, we have identified that the elevated expression of mutated ZNF469 impacts the prognosis and immune infiltration in LUAD, suggesting its potential as a diagnostic and prognostic biomarker in LUAD.
Humans ; Lung Neoplasms/genetics* ; Adenocarcinoma of Lung/genetics* ; China ; Prognosis ; Transcription Factors

Given the vital role of vasculature in solid tumors, the potential of vascular disrupting therapy in the treatment of triple-negative breast cancer (TNBC) is promising. In this study, we prepared the acid-sensitive liposome PPD/CA4P/Lip-Rap loaded with the vascular disrupting agent CA4P and the anti-angiogenic drug rapamycin (Rap) to explore the potential of the vascular disrupting strategy in TNBC. PPD/CA4P/Lip-Rap was characterized by ¹H NMR, dynamic light scattering, and transmission electron microscopy. Its drug loading and acid sensitivity were determined. The particle size of PPD/CA4P/Lip-Rap is 161.53 ± 1.89 nm, the zeta potential is -20.03 ± 0.9 mV and it demonstrated good drug release on acidic sensitivity responses. CCK-8 experiments proved that Rap can enhance the ability of CA4P to destroy tumor vascular endothelial cells. Rap can kill marginal residual tumor cells, suppress tumor recurrence. Nanocarriers can further enhance the therapeutic effect. Western blot (WB) showed that Rap decreased the expression of hypoxia-inducible factor-1α (HIF-1α) via the mTOR/p70S6K and mTOR/4E-BP1 pathways. Thus, tumor hypoxia activation and angiogenesis were inhibited. PPD/CA4P/Lip-Rap can effectively destroy tumor vessels, inhibit tumor angiogenesis and recurrence, and provide a new strategy for the treatment of TNBC by targeting disruption of tumor vessels.

With the rapid development of information technology,what has been widely used in the field of medical and health care includes the home detection of aging population in communities,intelligent health management,special patient positioning care management,information sharing,and interconnection management,which has also brought new opportunities for the innovative management of medical equipment in recent years.We have taken"sense,knowledge and action"as the core,and effectively improved the level of lean management of medical equipment through data acquisition,data modeling and analysis,and remote service or decision response.This paper aims to summarize the application and research progress of intelligent information technology in the lean management of medical equipment in order to provide new ideas for the refined management of medical equipment.

Objective:To investigate the effects of early postoperative nutritional management under enhanced recovery after surgery (ERAS) guidelines on nutritional biochemical indicators and length of hospital stay in patients undergoing lumbar fusion surgery. Method:Ninety-four patients who underwent lumbar posterior internal fixation + intervertebral fusion surgery in Department of Orthopedics Ⅲ of Ningxia Medical University General Hospital from January 2020 to March 2021 were randomly divided into an intervention group (n=47) and a control group (n=47). The intervention group received nutritional intervention by a clinical nutritionist at 2 hours after anesthesia recovery, and the control group started to eat liquid diet at 6 hours after anesthesia recovery. The protein-calorie intake, blood glucose, total protein, albumin, hemoglobin, postoperative hospitalization time and total hospitalization time of the two groups were observed. Results:The protein-calorie intake of the intervention group was higher than that of the control group on the day of surgery and the first 3 days after surgery, with statistically significant differences (P<0.05). The blood glucose level of the intervention group was lower than that of the control group on the first day after surgery, with statistically significant differences (P<0.05). The total protein level of the intervention group was higher than that of the control group on the third day after surgery, with statistically significant differences (P<0.05). The albumin and hemoglobin levels of the intervention group were higher than those of the control group on the first and third days after surgery, with statistically significant differences (P<0.05). The incidence of abdominal distension and the length of hospital stay in the intervention group were lower than those in the control group, with statistically significant differences (P<0.05). Conclusion:Early postoperative nutritional management has a certain effect on improving nutritional and biochemical indicators and shortening the length of hospital stay in patients undergoing lumbar fusion surgery.

AIM To investigate the consistency of chemical constituents between formula granules and standard decoction of Coptidis Rhizoma.METHODS Eighteen batches of standard decoctions were prepared,after which the extraction rate and contents,transfer rates of magnolflorine,jatrorrhizine,columbamine,epiberberine,coptisine,palmatine,berberin were determined,HPLC characteristic chromatograms were established.RESULTS There were 11 common peaks in the characteristic chromatograms of 18 batches of standard decoctions and 24 batches of formula granules with the similarities of 0.861-1.000,which were clusterd into two categories.The formula granules and standard decoction demonstrated approximated extraction rate and contents,transfer rates of index constituents.CONCLUSION The chemical constituents between formula granules and standard decoction of Coptidis Rhizoma display good consistency,which can provide references for the quality control,process research and clinical application of the former.