Objective To investigate the therapeutic effect and mechanism of astragaloside Ⅳ on systemic lupus erythematosus(SLE)mice.Methods A total of 40 female spontaneous MRL/lpr SLE model mice were randomly divided into five groups:model group,Prednisone group,astragaloside Ⅳ group,astragaloside Ⅳ+CHPG[nuclear factor KappaB(NF-κB)pathway activator]group and astragaloside Ⅳ+Nigerian[NOD-like receptor family pyrin domain containing protein 3(NLRP3)activator]group,with eight mice in each group.Eight female MRL/MpJ mice were used as normal group.During the administration,the body mass was weighted.After administration,the spleen,thymus and kidney were weighted,and the organ index was calculated.The 24-hour urinary protein level in urine samples,the biochemical indexes of creatinine(SCr),blood urea nitrogen(BUN),autoantibodies[antinuclear antibody(ANA),anti-double-stranded DNA(dsDNA)antibody,anti-snRNP/Sm antibody]and inflammatory mediators[interleukin(IL)-1β,IL-18]in blood samples were detected.The pathological damage of renal tissue was observed by hematoxylin-eosin(HE)staining,and the fibrosis of renal tissue was observed by Masson staining.The expressions of NF-κB/NLRP3 inflammasome pathway-related proteins in kidney and spleen tissues were detected by Western Blot.Results Compared with the model group,the body mass of mice in prednisone group and astragaloside Ⅳ group increased,the spleen index,thymus index and kidney index were decreased,the serum levels of ANA antibody,anti-dsDNA antibody and anti-snRNP/Sm antibody were decreased,the levels of SCr,BUN and 24-hour urine protein were decreased,the levels of IL-1 βand IL-18 wrere decreased,the ratios of p-p65/p65,p-IKBα/IKBα,cleaved caspase-1/pro caspase-1 and the relative expression of NLRP3 protein in kidney and spleen tissues were decreased(all P＜0.05),and the pathological damage and fibrosis of renal tissue in SLE mice were alleviated,there being no significant difference between the two administration groups(P＞0.05).NF-κB activator and NLRP3 inflammasome activator eliminated the improvement of astragaloside Ⅳ on the above indexes in SLE mice to a certain extent.Conclusion Astragaloside Ⅳ can improve the immune function of SLE mice,reduce renal injury and inflammatory response,and its mechanism may be related to its inhibition of the activation of NF-κB/NLRP3 inflammasome pathway.

Humans ; Nasal Cavity ; Melanoma ; Skin Neoplasms ; Paranasal Sinuses

Objective:To establish an isotope dilution liquid chromatography-tandem mass spectrometry (ID-LC-MS/MS) method for the determination of L-tryptophan and its metabolites in serum.Methods:The methodology was established and evaluated using serum samples collected from 166 healthy subjects undergoing physical examinations at West China Hospital from November 2022 to January 2023 were collected. Isotope-labeled markers of L-tryptophan (Trp), L-kynurenine (Kyn), and kynurenic acid (KA) were used as internal standards. After protein precipitation treatment of serum samples, LC-MS/MS was used to determine Trp, Kyn, and KA simultaneously. The selectivity, specificity, linearity, detection limit (LOD), quantification limit (LOQ), carry-over, precision, recovery rate, matrix effect, and dilution integrity of the method were evaluated.Results:The linearity of Trp, Kyn, and KA was demonstrated to be 0.999. The LODs were 0.10 μmol/L, 0.01 μmol/L and 1.00 nmol/L, respectively. The LOQs were 0.20 μmol/L, 0.04 μmol/L and 2.00 nmol/L, respectively. The intra-batch precision and inter-batch precision were below<10%. The average recovery rate and the relative matrix effect were all about 100%. The samples over the upper limit of quantitation can be diluted up to 16 times. The Trp concentration, Kyn concentration, KA concentration, Kyn/Trp ratio, and KA/Kyn ratio in serum of healthy subjects were 59.55±10.92 μmol/L, 1.85±0.43 μmol/L, 39.89±17.93 nmol/L, (31.64±8.19)×10 -3 and 21.51±6.72, respectively. Conclusion:An ID-LC-MS/MS method was successfully established for the quantitative determination of Trp, Kyn, and KA in serum. The method proved to be simple, rapid, sensitive, accurate, and reliable, providing robust support for clinical research related to these analytes.

Objective To evaluate the effectiveness of pharyngeal swabs combined with anal swabs as multidrug-resistant organism(MDRO)admission screening for patients in intensive care unit(ICU),and provide reference for healthcare-associated infection(HAI)prevention and control strategies.Methods Patients who underwent MDRO admission screening by pharyngeal swabs combined with anal swabs within 24 hours of admission to an ICU of a hospital in Shanghai from August 1 to December 31,2022 were included as the experimental group,and those who underwent MDRO admission screening only by pharyngeal swabs from August 1 to December 31,2021 were as the control group.Positive rate of screening,occurrence and pathogen of HAI between the two groups,as well as the sensitivity and specificity of combined admission screening for MDRO in the experimental group were compared.Results A total of 917 patients were included in the study,with 442 cases in the experimental group and 475 cases in the control group.The positive rates of admission screening for MDRO in the experimental and control groups were 7.40％and 3.37％,respectively.The incidences of HAI with MDRO in the experimental and control groups were 2.71％and 5.68％,respectively.Incidences of digestive system HAI with MDRO in the experimental and control groups were 0.68％and 2.32％,respectively.Differences were all statistically significant(all P＜0.05).The area under the ROC curve of admission screening by pharyngeal swabs combined with anal swabs for predicting HAI with MDRO in patients were 0.897(P＜0.01,95％CI:0.802-0.993).The sensitivity and specificity of admi-ssion screening for MDRO by pharyngeal swabs combined with anal swabs in the experimental group were 72.73％and 97.65％,respectively.Conclusion The combination of pharyngeal swabs and anal swabs can be used as an ICU admission screening method for MDRO,and has an important clinical application value.

The finite element method (FEM) is a mathematical method for obtaining approximate solutions to a wide variety of engineering problems. With the development of computer technology, it is gradually applied to the study of biomechanics of human body. The application of the combination of FEM and biomechanics in exploring the relationship between vascular injury and disease, and pathological mechanisms will be a technological innovation for traditional forensic medicine. This paper reviews the construction and development of human vascular FEM modeling, and its research progress on the vascular biomechanics. This paper also looks to the application prospects of FEM modeling in forensic pathology.
Humans ; Computer Simulation ; Models, Biological ; Biomechanical Phenomena ; Finite Element Analysis ; Forensic Medicine

This study aimed to investigate the effect and mechanism of Zuogui Jiangtang Qinggan Formula(ZGJTQG) on the glucolipid metabolism of type 2 diabetes mellitus(T2DM) complicated with non-alcoholic fatty liver disease(NAFLD). NAFLD was induced by a high-fat diet(HFD) in MKR mice(T2DM mice), and a model of T2DM combined with NAFLD was established. Forty mice were randomly divided into a model group, a metformin group(0.067 g·kg~(-1)), and high-and low-dose ZGJTQG groups(29.64 and 14.82 g·kg~(-1)), with 10 mice in each group. Ten FVB mice of the same age were assigned to the normal group. Serum and liver tissue specimens were collected from mice except for those in the normal and model groups after four weeks of drug administration by gavage, and fasting blood glucose(FBG) and fasting insulin(FINS) levels were measured. The levels of total cholesterol(TC), triglyceride(TG), and low-density lipoprotein(LDL) were detected by the single reagent GPO-PAP method. Very low-density lipoprotein(VLDL) was detected by enzyme-linked immunosorbent assay(ELISA). Alanine aminotransferase(ALT) and aspartate ami-notransferase(AST) were determined by the Reitman-Frankel assay. The pathological changes in the liver were observed by hematoxylin-eosin(HE) staining and oil red O staining. Real-time fluorescence-based quantitative polymerase chain reaction(real-time PCR) and Western blot were adopted to detect the mRNA and protein expression of forkhead transcription factor O1(FoxO1), microsomal triglyceride transfer protein(MTP), and apolipoprotein B(APOB) in the liver. The results showed that high-dose ZGJTQG could signi-ficantly reduce the FBG and FINS levels(P<0.05, P<0.01), improve glucose tolerance and insulin resistance(P<0.05, P<0.01), alleviate the liver damage caused by HFD which was reflected in improving liver steatosis, and reduce the serum levels of TC, TG, LDL, VLDL, ALT, and AST(P<0.05, P<0.01) in T2DM mice combined with NAFLD. The findings also revealed that the mRNA and protein expression of FoxO1, MTP, and APOB in the liver was significantly down-regulated after the intervention of high-dose ZGJTQG(P<0.05, P<0.01). The above study showed that ZGJTQG could effectively improve glucolipid metabolism in T2DM combined with NAFLD, and the mechanism was closely related to the regulation of the FoxO1/MTP/APOB signaling pathway.
Mice ; Animals ; Non-alcoholic Fatty Liver Disease/metabolism* ; Diabetes Mellitus, Type 2/metabolism* ; Liver ; Lipoproteins, LDL/metabolism* ; Signal Transduction ; Diet, High-Fat/adverse effects* ; RNA, Messenger/metabolism*

Chest trauma is one of the most common injuries. Venous thromboembolism (VTE) as a common complication of chest trauma seriously affects the quality of patients′ life and even leads to death. Although there are some consensus and guidelines on the prevention and treatment of VTE at home and abroad, the current literatures lack specificity considering the diagnosis, treatment and prevention of VTE in patients with chest trauma have their own characteristics, especially for those with blunt trauma. Accordingly, China Chest Injury Research Society and editorial board of Chinese Journal of Traumatology organized relevant domestic experts to jointly formulate the Chinese expert consensus on the diagnosis, treatment and prevention of chest trauma venous thromboembolism associated with chest trauma (2022 version). This consensus provides expert recommendations of different levels as academic guidance in terms of the characteristics, clinical manifestations, risk assessment, diagnosis, treatment, and prevention of chest trauma-related VTE, so as to offer a reference for clinical application.

The increasing disease burden caused by cancer has become a major global public health problem. Studies have shown that diet and lifestyle changes may play an important role in cancer prevention. Oxidative balance score (OBS) is a composite measure of an individual's oxidative balance by integrating both antioxidant and pro-oxidant components of dietary and lifestyle factors. At present, a number of studies have investigated the relationship between oxidative balance score and cancer occurrence and prognosis. This article reviews the relationship between the twoe, and no partner. At the same time, it is necessary to strengthen the utilization of NBPHS to promote the change of their health awareness and health behavior.

OBJECTIVE: To investigate the clinical value of oligoclonal bands (OB) in patients with multiple myeloma (MM). METHODS: The laboratory test and clinical data of 624 newly diagnosed MM patients admitted to Blood Diseases Hospital of Chinese Academy of Medical Sciences from January 2013 to December 2019 were retrospectively analyzed, including 30 patients with OB, and the clinical characteristics, treatment effects and survival of OB and non-OB patients were analyzed and compared. RESULTS: OB occurred in 11.8% (22/187) of patients who received autologous stem cell transplantation(ASCT) and only 1.8% (8/437) of patients who did not receive ASCT (P=0.000). The median time to the appearance of oligoclonal bands was 3.2(0.6-10.5) months after transplantation. The M protein types of oligoclonal bands mainly include IgG κ, IgG λ, IgM λ and λ light chains. In the presence of oligoclonal bands, 90% of patients were evaluated as complete remission (CR) and above. There were no statistically significant differences in disease stage, tumor burden, and genetic abnormalities between OB and non-OB patients. Among the all patients, the prognosis of OB patients was significantly better than that of non-OB patients, and OB patients showed deeper disease remission (significantly higher CR rate, MRD negative rate, and longer MRD negative duration). Among patients who underwent ASCT, OB patients showed earlier immune recovery, but the depth of treatment response and survival outcomes were similar between OB and non-OB patients, it was no statistically difference. Although OB patients showed earlier immune reconstitution, this did not translate into better survival, suggesting that the better prognosis of OB patients was mainly related to deeper and durable remission rather than early immune reconstitution. Further analysis in patients who received ASCT and obtained MRD negative indicated that there was no additional survival benefit in patients with OB. CONCLUSION The better prognosis of OB patients may be related to the deeper treatment response, but not to the early immune reconstitution. The appearance of OB is only a sign of deep remission and early immune reconstitution in patients, it cannot be translated into survival benefit of MM patients.
Hematopoietic Stem Cell Transplantation ; Humans ; Immunoglobulin G ; Immunoglobulin M ; Multiple Myeloma ; Oligoclonal Bands ; Retrospective Studies ; Transplantation, Autologous

Background::NOTCH1 mutation is an essential molecular biologic aberration in chronic lymphocytic leukemia (CLL). CLL patients with NOTCH1 mutation have shown an unfavorable survival and a poor response to chemoimmunotherapy. This study aims to present the mechanisms of adverse prognosis caused by NOTCH1 mutation from the perspective of the splicing factor heterogeneous nuclear ribonucleoprotein A1 (hnRNPA1). Methods::The microarray data in Gene Expression Omnibus datasets were analyzed by bioinformatics and the function of hnRNPA1 was checked by testing the proliferation and apoptosis of CLL-like cell lines. Afterward, quantitative reverse transcription-polymerase chain reaction and Western blotting were applied to explore the relationship among NOTCH1, c-Myc, and hnRNPA1.Results::RNA splicing was found to play a vital part in NOTCH1-mutated CLL cells; hence, hnRNPA1 was selected as the focus of this study. Higher expression of hnRNPA1 validated in primary NOTCH1-mutated CLL samples could promote proliferation and inhibit apoptosis in CLL. The expression of hnRNPA1 increased when NOTCH1 signaling was activated by transfection with NOTCH1 intracellular domain (NICD)-overexpressed adenovirus vector and declined after NOTCH1 signaling was inhibited by NOTCH1-shRNA. Higher expression of c-Myc was observed in NICD-overexpressed cells and hnRNPA1 expression was downregulated after applying c-Myc inhibitor 10058-F4. Moreover, in NICD-overexpressed cells, hnRNPA1 expression decreased through c-Myc inhibition. Conclusion::Overexpression of c-Myc-dependent hnRNPA1 could promote proliferation and inhibit apoptosis in NOTCH1- mutated CLL cells, which might partly account for the poor prognosis of patients with NOTCH1 mutation.