Chrysophanol(Chr)and physcion(Phy)are primary active ingredients of a well-known traditional Chinese medicine namely rhubarb(Chinese name:Dahuang),and their glucuronides have been revealed as the dominant forms presenting in rats after oral administration.Either Chr or Phy has two glycosylation sites,resulting in a pair of positional isomers for glucuronides of either compound(CG1&CG2 and PG1&PG2).To confirmatively identify these glucuronides,energy-resolved mass spectrometry(ER-MS)was used to pursue the fragmentation trajectories of the targeted fragment ions,and the resultant breakdown graphs that were described by the optimal collision energy(OCE)were expected to exhibit the differences of glycosidic bond cleavage between the isomers.Quantum chemical calculation was thereafter conducted to produce the bond dissociation energy(BDE)of the glycosidic bonds.The isomers were unambiguously identified through applying the positive correlation rule between OCE and BDE.Fortunately,the glucuronides of Chr and Phy in vivo were observed through liver microsomes incubationin vitro.ER-MS was utilized to collect the Gaussian-shaped breakdown graphs in response to the neutral loss of 176 Da,and the absolute values of OCE were compared between positional isomers.The results revealed that CG1(-32.31 eV)>CG2(-31.61 eV),and nonetheless,PG1(-30.00 eV)Chr-8-GluA(-48.787 kJ/mol),and nonetheless,Phy-1-GluA(-48.672 kJ/mol)

Objective:To evaluate the diagnostic performance of the Prostate Imaging Reporting and Data System version 2.1(PI-RADS v2.1)for clinically significant prostate cancer(CSPCa)in the peripheral zone(PZ),transitional zone(TZ)and multiple zones(MZs).Methods:We retrospectively studied the clinical data on 108 patients undergoing multiparametric magnetic resonance imaging(mpMRI)and transperineal prostate biopsy in our hospital from January 2021 to January 2023.Using PI-RADS v2.1,we ex-amined the MR images of the patients with suspected PCa,compared the PI-RADS v2.1 scores with the results of prostate biopsy,and analyzed the correlation of the PI-RADS v2.1 scores with CSPCa.We calculated the area under the receiver operating characteristic(ROC)curve(AUC),and described the diagnostic performance of PI-RADS v2.1 for CSPCa in the PZ,TZ and MZs.Results:Transperineal prostate puncture biopsy was successfully completed in all the patients,which revealed 66(61.11％)cases of CSPCa with Gleason score(GS)7-10.Suspected CSPCa was observed in 45(95.74％)of the 47 PZ lesions,8(47.06％)of the 17 TZ le-sions,and 40(90.91％)of the 44 MZ lesions.The PZ,TZ and MZ lesions diagnosed by PI-RADS v2.1 were significantly correlated with CSPCa(r=0.492,P＜0.001).The AUCs of PI-RADS v2.1 for PZ,TZ and MZs were 0.644,0.732 and 0.811,with specificities of 66.8％,57.6％and 62.1％,and sensitivities of 57.2％,78.4％and 93.2％,respectively.The negative predictive values were 46.5％,85.7％and 79.2％,and the positive predictive values 76.2％,43.4％and 84.8％,respectively.Conclusion:The PI-RADS v2.1 score has a high diagnostic value for CSPCa in the PZ,TZ and MZs,with the best performance for that in the MZs.

Objective To investigate the correlation between the level of N-terminal pro-Brain natriuretic peptide(NT-proBNP)and cardiorespiratory fitness following acute exposure to high altitude.Methods Forty-six subjects were recruited from the Second Affiliated Hospital of Army Medical University in June 2022,including 19 males and 27 females.After completing cardiopulmonary exercise test(CPET),serological detection of myocardial cell-related markers,and multiple metabolites at a plain altitude(300 meters above sea level),all subjects flew to a high-altitude location(3900 meters above sea level).Biomarker testing and CPET were repeated on the second and third days after arrival at high altitude.Changes in serum biomarker and key CPET indicators before and after rapid ascent to high altitude were compared,and the correlation between serum levels of various myocardial cell-related markers and metabolites and high altitude cardiorespiratory fitness was analyzed.Results Compared with the plain altitude,there was a significant decrease in maximal oxygen uptake after rapid ascent to high altitude[(25.41±6.20)ml/(kg.min)vs.(30.17±5.01)ml/(kg.min),P<0.001].Serum levels of NT-proBNP,Epinephrine(E),plasma renin activity(PRA),angiotensin Ⅱ(Ang Ⅱ),angiotensin-converting enzyme 2(ACE2)and leptin(LEP)significantly increased,with all differences being statistically significant(P<0.05)after acute high altitude exposure.In contrast,no statistically significant differences were observed for creatine kinase MB(CK-MB),cardiac troponin I(cTnI),myoglobin(Myo)and norepinephrine(NE)(P>0.05).Correlation analysis showed a significant negative correlation between NT-proBNP at plain altitude(r=-0.768,P<0.001)and at high altitude(r=-0.791,P<0.001)with maximal oxygen uptake at high altitude.Multivariate linear regression analysis indicated that maximal oxygen uptake at plain altitude(t=2.069,P=0.045),NT-proBNP at plain altitude(t=-2.436,P=0.020)and at high altitude(t=-3.578,P=0.001)were independent influencing factors of cardiorespiratory fitness at high altitude.Conclusion Cardiorespiratory fitness significantly decreases after rapid ascent to high altitude,and the baseline NT-proBNP level at plain altitude is closely related to cardiorespiratory fitness at high altitude,making it a potential predictor indicator for high altitude cardiorespiratory fitness.

This study was aimed at comparing performance differences among three metagenomic sequencing platforms,MGISEQ-2000,Illumina NextSeq 2000,and Ion GeneStudio S5 Plus,to optimize the sequencing process for trace samples.The three sequencing platforms were used to perform high-throughput sequencing on DNA standards and simulated samples.Through analysis of the quality of raw data and microbial detection capabilities,systematic differences among platforms were compared.The sequencing results were optimized for trace samples by incorporation of exogenous nucleic acids during the li-brary preparation process.In terms of data output per batch and base quality,MGISEQ-2000 surpassed the other two plat-forms.Illumina NextSeq 2000 had the lowest proportion of duplicate reads,whereas Ion GeneStudio S5 Plus had the highest proportion,and significant differences were observed across platforms(P＜0.001).In sequencing uniformity,MGISEQ-2000 and Illumina NextSeq 2000 were superior to Ion GeneStudio S5 Plus.MGISEQ-2000 provided a substantial advantage in microbial detection capability(P＜0.001),but the advantage diminished with decreasing bacterial fluid concentration.Ion GeneStudio S5 Plus had the shortest duration for single-batch sequencing.Moreo-ver,for trace samples with DNA content ≤0.05 ng,the experi-mental group(with added exogenous nucleic acids)achieved a higher number of reads than the control group(without exogenous nucleic acids),with a 11.09±8.03 fold increase.In conclu-sion,the different sequencing platforms each had advantages and disadvantages,thus allowing researchers to choose the appro-priate platform according to specific needs.Furthermore,the addition of exogenous nucleic acids improved the microorganism detection efficiency,and provided better support for subsequent diagnosis and evaluation of results.

Objective:To investigate the protein expression of human epidermal growth factor receptor 2 (c-erbB2), CyclinD1, and protein kinase B1 (Akt1) in papillary thyroid carcinoma tissue.Methods:A retrospective study was conducted to collect papillary thyroid carcinoma tissues, adjacent tissues, pathological and medical records, as well as one year follow-up data of patients ( n = 117) diagnosed with papillary thyroid carcinoma at Huai'an Cancer Hospital in Jiangsu Province from January 2021 to October 2022. The protein expression of c-erbB2, CyclinD1, and Akt1 were determined by immunohistochemistry. The positive rates of c-erbB2, CyclinD1, and Akt1 proteins in cancerous tissue and adjacent tissues, and cancerous tissue of patients with different clinical features and recurrence status were compared. Results:There were statistically significant differences in the positive rates of c-erbB2 [36.75% (43/117) vs 5.98% (7/117)], CyclinD1 [47.86% (56/117) vs 6.84% (8/117)], and Akt1 proteins [64.96% (76/117) vs 11.97% (14/117)] between the cancerous tissue and adjacent tissue of patients with papillary thyroid carcinoma (χ 2 = 32.96, 49.55, 69.41, P < 0.001). There were statistically significant differences in the positive rates of c-erbB2, CyclinD1, and Akt1 proteins in cancerous tissues of patients with different tumor node metastasis (TNM) classification staging, invasion of the capsule, and lymph node metastasis (χ 2 = 40.67, 20.47, 12.07, 13.68, 7.25, 9.16, 22.04, 27.18, 46.31, P < 0.05). There was no statistically significant difference in the positive rates of c-erbB2, CyclinD1, and Akt1 proteins in cancerous tissues of patients with different genders, ages, smoking history, drinking history, maximum tumor diameter, and whether the tumor was multifocal or accompanied by Hashimoto's thyroiditis ( P > 0.05). The follow-up results of 117 patients with papillary thyroid carcinoma showed that there were 15 cases of recurrence and 102 cases of no recurrence. The positive rates of c-erbB2, CyclinD1, and Akt1 proteins in the cancerous tissue of the recurrence group were higher than those of the non recurrence group (χ 2 = 4.00, 4.47, 6.09, P < 0.05). Conclusion:The positive rates of c-erbB2, CyclinD1, and Akt1 proteins in papillary thyroid carcinoma tissues are relatively high, and are closely related to TNM classification staging, invasion of the capsule, lymph node metastasis, and recurrence.

Objective:To investigate the protein expression of human epidermal growth factor receptor 2 (c-erbB2), CyclinD1, and protein kinase B1 (Akt1) in papillary thyroid carcinoma tissue.Methods:A retrospective study was conducted to collect papillary thyroid carcinoma tissues, adjacent tissues, pathological and medical records, as well as one year follow-up data of patients ( n = 117) diagnosed with papillary thyroid carcinoma at Huai'an Cancer Hospital in Jiangsu Province from January 2021 to October 2022. The protein expression of c-erbB2, CyclinD1, and Akt1 were determined by immunohistochemistry. The positive rates of c-erbB2, CyclinD1, and Akt1 proteins in cancerous tissue and adjacent tissues, and cancerous tissue of patients with different clinical features and recurrence status were compared. Results:There were statistically significant differences in the positive rates of c-erbB2 [36.75% (43/117) vs 5.98% (7/117)], CyclinD1 [47.86% (56/117) vs 6.84% (8/117)], and Akt1 proteins [64.96% (76/117) vs 11.97% (14/117)] between the cancerous tissue and adjacent tissue of patients with papillary thyroid carcinoma (χ 2 = 32.96, 49.55, 69.41, P < 0.001). There were statistically significant differences in the positive rates of c-erbB2, CyclinD1, and Akt1 proteins in cancerous tissues of patients with different tumor node metastasis (TNM) classification staging, invasion of the capsule, and lymph node metastasis (χ 2 = 40.67, 20.47, 12.07, 13.68, 7.25, 9.16, 22.04, 27.18, 46.31, P < 0.05). There was no statistically significant difference in the positive rates of c-erbB2, CyclinD1, and Akt1 proteins in cancerous tissues of patients with different genders, ages, smoking history, drinking history, maximum tumor diameter, and whether the tumor was multifocal or accompanied by Hashimoto's thyroiditis ( P > 0.05). The follow-up results of 117 patients with papillary thyroid carcinoma showed that there were 15 cases of recurrence and 102 cases of no recurrence. The positive rates of c-erbB2, CyclinD1, and Akt1 proteins in the cancerous tissue of the recurrence group were higher than those of the non recurrence group (χ 2 = 4.00, 4.47, 6.09, P < 0.05). Conclusion:The positive rates of c-erbB2, CyclinD1, and Akt1 proteins in papillary thyroid carcinoma tissues are relatively high, and are closely related to TNM classification staging, invasion of the capsule, lymph node metastasis, and recurrence.

Background: and Purpose We aimed to determine the clinical features of Miller Fisher syndrome (MFS) in southern China and compare them with those presenting in other countries. Methods: We collected the medical records of patients diagnosed with MFS during 2013–2016.We analyzed the age, sex, onset season, precursor events, clinical symptoms and signs, findings of nerve conduction studies (NCS), cerebrospinal fluid (CSF), therapeutic remedies, nadir time, and length of hospital stay of patients with MFS in southern China. We concurrently compared the differences between urban and rural areas and between patients with incomplete ophthalmoplegia (IO) and complete ophthalmoplegia (CO). Results: The study enrolled 72 patients: 36 from rural areas and 36 from urban areas, and 50 males and 22 females. The mean age at onset was 47.72 years, and 30 (41.7%) and 21 (29.2%) patients developed MFS in spring and winter, respectively. The typical triad of ophthalmoplegia, ataxia, and areflexia was observed in 50 (69.4%) patients. A history of upper respiratory tract infection 1 week before onset was found in 52.8% of the patients, while 5.6% experienced gastrointestinal infections and 48 (73.8%) exhibited albuminocytological dissociation in the CSF study. Only 26 (36.1%) patients presented abnormalities in NCS. Moreover, restricted outward eyeball movement presented in 83.5% of the patients with classic MFS and acute ophthalmoplegia, and bilateral symmetrical ophthalmoplegia presented in 64.2%. With the exception of the higher proportion of NCS abnormalities in urban areas (47.2% vs. 25.0%), urban and rural differences were insignificant regarding sex ratio, age at onset, high-incidence season, precursor events, disease characteristics, and albuminocytological dissociation in the CSF. Furthermore, patients with CO were older than those with IO (64.53±7.69 vs. 43.19±14.40 years [mean±standard deviation], p<0.001). Conclusions The patients with MFS were mostly male and middle-aged, and most presented in winter and (especially) spring. More than half of the patients had clear precursor events, most of which were classic MFS with the typical triad. More than 70% of the patients presented albuminocytological dissociation in the CSF. NCS abnormalities were uncommon in MFS. The age at onset was lower in patients with IO than in patients with CO; bilateral symmetrical extraocular muscle paralysis was the most common symptom, and the external rectus was the most frequently involved muscle.

Objective: To evaluate the efficacy and safety of intravenous iron supplementation in patients with recurrent iron deficiency anemia (IDA) . Methods: This retrospective analysis of 90 patients with recurrent IDA from May 2012 to December 2021 was conducted, comparing the efficacy and safety of the intravenous iron therapy group and the oral iron therapy group. Results: Among the 90 patients with recurrent IDA, 20 were males and 70 were females, with a median age of 40 (range: 14-85) years. A total of 60 patients received intravenous iron supplementation and 30 received oral iron supplementation. The hematologic response rates in the intravenous iron group were significantly higher than those in the oral iron group at 4 and 8 weeks after treatment [80.0% (48/60) vs 3.3% (1/30) and 96.7% (58/60) vs 46.7% (14/30), all P<0.001, respectively]. The median increase in hemoglobin levels was also significantly higher in the intravenous iron group than in the oral iron group [38 (4, 66) g/L vs 7 (1, 22) g/L at week 4 and 44.5 (18, 80) g/L vs 19 (3, 53) g/L at week 8, all P<0.001]. The intravenous iron group had a significantly higher proportion of patients who achieved normal hemoglobin levels than the oral iron group (55.0% vs 0 and 90% vs 43.3%, all P<0.001, respectively). Iron metabolism indicators were tested before and after 8 weeks of treatment in 26 and 7 patients in the intravenous and oral iron groups, respectively. The median increase in serum ferritin (SF) levels in the intravenous iron group 8 weeks after treatment was 113.7 (49.7, 413.5) μg/L, and 54% (14/26) of these patients had SF levels of ≥100 μg/L, which was significantly higher than the median increase in SF levels in the oral iron group [14.0 (5.8, 84.2) μg/L, t=4.760, P<0.001] and the proportion of patients with SF levels of ≥100 μg/L (P=0.013). The incidence of adverse reactions was 3.3% (2/60) in the intravenous iron group, which was significantly lower than that in the oral iron group [20.0% (6/30), P=0.015]. Conclusion: Intravenous iron supplementation is more effective for hematologic response, faster hemoglobin increase, and higher iron storage replenishment rates compared with oral iron supplementation in patients with recurrent IDA, and it is well tolerated by patients.
Male ; Female ; Humans ; Adolescent ; Young Adult ; Adult ; Middle Aged ; Aged ; Aged, 80 and over ; Anemia, Iron-Deficiency/epidemiology* ; Sucrose/therapeutic use* ; Ferric Compounds/therapeutic use* ; Retrospective Studies ; Iron/therapeutic use* ; Hemoglobins/therapeutic use*

The aim of this study was to investigate the effect and molecular mechanism of Xuebijing Injection in the treatment of sepsis-associated acute respiratory distress syndrome(ARDS) based on network pharmacology and in vitro experiment. The active components of Xuebijing Injection were screened and the targets were predicted by the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP). The targets of sepsis-associated ARDS were searched against GeneCards, DisGeNet, OMIM, and TTD. Weishengxin platform was used to map the targets of the main active components in Xuebijing Injection and the targets of sepsis-associated ARDS, and Venn diagram was established to identify the common targets. Cytoscape 3.9.1 was used to build the "drug-active components-common targets-disease" network. The common targets were imported into STRING for the building of the protein-protein interaction(PPI) network, which was then imported into Cytoscape 3.9.1 for visualization. DAVID 6.8 was used for Gene Ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) enrichment of the common targets, and then Weishe-ngxin platform was used for visualization of the enrichment results. The top 20 KEGG signaling pathways were selected and imported into Cytoscape 3.9.1 to establish the KEGG network. Finally, molecular docking and in vitro cell experiment were performed to verify the prediction results. A total of 115 active components and 217 targets of Xuebijing Injection and 360 targets of sepsis-associated ARDS were obtained, among which 63 common targets were shared by Xuebijing Injection and the disease. The core targets included interleukin-1 beta(IL-1β), IL-6, albumin(ALB), serine/threonine-protein kinase(AKT1), and vascular endothelial growth factor A(VEGFA). A total of 453 GO terms were annotated, including 361 terms of biological processes(BP), 33 terms of cellular components(CC), and 59 terms of molecular functions(MF). The terms mainly involved cellular response to lipopolysaccharide, negative regulation of apoptotic process, lipopolysaccharide-mediated signaling pathway, positive regulation of transcription from RNA polyme-rase Ⅱ promoter, response to hypoxia, and inflammatory response. The KEGG enrichment revealed 85 pathways. After diseases and generalized pathways were eliminated, hypoxia-inducible factor-1(HIF-1), tumor necrosis factor(TNF), nuclear factor-kappa B(NF-κB), Toll-like receptor, and NOD-like receptor signaling pathways were screened out. Molecular docking showed that the main active components of Xuebijing Injection had good binding activity with the core targets. The in vitro experiment confirmed that Xuebijing Injection suppressed the HIF-1, TNF, NF-κB, Toll-like receptor, and NOD-like receptor signaling pathways, inhibited cell apoptosis and reactive oxygen species generation, and down-regulated the expression of TNF-α, IL-1β, and IL-6 in cells. In conclusion, Xuebijing Injection can regulate apoptosis and response to inflammation and oxidative stress by acting on HIF-1, TNF, NF-κB, Toll-like receptor, and NOD-like receptor signaling pathways to treat sepsis-associated ARDS.
Humans ; Network Pharmacology ; Vascular Endothelial Growth Factor A ; NF-kappa B ; Interleukin-6 ; Lipopolysaccharides ; Molecular Docking Simulation ; Respiratory Distress Syndrome ; Tumor Necrosis Factor-alpha ; Sepsis/genetics* ; NLR Proteins

This study aimed to investigate the effective substances and mechanism of Yishen Guluo Mixture in the treatment of chronic glomerulonephritis(CGN) based on metabolomics and serum pharmacochemistry. The rat model of CGN was induced by cationic bovine serum albumin(C-BSA). After intragastric administration of Yishen Guluo Mixture, the biochemical indexes related to renal function(24-hour urinary protein, serum urea nitrogen, and creatinine) were determined, and the efficacy evaluations such as histopathological observation were carried out. The serum biomarkers of Yishen Guluo Mixture in the treatment of CGN were screened out by ultra-performance liquid chromatography-quadrupole time-of-flight/mass spectrometry(UPLC-Q-TOF-MS) combined with multivariate statistical analysis, and the metabolic pathways were analyzed. According to the mass spectrum ion fragment information and metabolic pathway, the components absorbed into the blood(prototypes and metabolites) from Yishen Guluo Mixture were identified and analyzed by using PeakView 1.2 and MetabolitePilot 2.0.4. By integrating metabolomics and serum pharmacochemistry data, a mathematical model of correlation analysis between serum biomarkers and components absorbed into blood was constructed to screen out the potential effective substances of Yishen Guluo Mixture in the treatment of CGN. Yishen Guluo mixture significantly decreased the levels of 24-hour urinary protein, serum urea nitrogen, and creatinine in rats with CGN, and improved the pathological damage of the kidney tissue. Twenty serum biomarkers of Yishen Guluo Mixture in the treatment of CGN, such as arachidonic acid and lysophosphatidylcholine, were screened out, involving arachidonic acid metabolism, glycerol phosphatide metabolism, and other pathways. Based on the serum pharmacochemistry, 8 prototype components and 20 metabolites in the serum-containing Yishen Guluo Mixture were identified. According to the metabolomics and correlation analysis of serum pharmacochemistry, 12 compounds such as genistein absorbed into the blood from Yishen Guluo Mixture were selected as the potential effective substances for the treatment of CGN. Based on metabolomics and serum pharmacochemistry, the effective substances and mechanism of Yishen Guluo Mixture in the treatment of CGN are analyzed and explained in this study, which provides a new idea for the development of innovative traditional Chinese medicine for the treatment of CGN.
Animals ; Rats ; Arachidonic Acid ; Biomarkers/blood* ; Blood Proteins ; Chromatography, High Pressure Liquid ; Creatinine ; Drugs, Chinese Herbal/therapeutic use* ; Glomerulonephritis/metabolism* ; Metabolomics ; Urea ; Chronic Disease ; Disease Models, Animal ; Complex Mixtures/therapeutic use*