AIM: To establish a sensitive method for quantitative determination of astragaloside Ⅳ (AGS-Ⅳ) in plasma and a preliminary evaluation of its pharmacokinetics parameters in intact rats. METHODS: A liquid chromatography-electrospray ionization-mass spectrometry (LC-ESI-MS) was applied for determining AGS-Ⅳ in plasma by using digoxin as the internal standard (I.S.). Six rats were given AGS-Ⅳ 2.0 mg/kg by intravenous infusion for 5 min. Blood samples were drawn intermittently with each intact rat from left femoral artery at 0.025, 0.05, 0.1, 0.25, 0.5, 1, 2, 4, 6, 10, 14 and 24 h after medication. The samples were prepared by solid phase extraction and analyzed through a triple quadrupole mass spectrometer equipped with an electrospary probe. The samples were monitored in selected ion recording (SIR) mode of positive ions by using target ions at m/z 807.5 for AS- Ⅳand at m/z 803.5 for I.S. RESULTS: Calibration curves were linear over the ranges 1-1 000 ng/mL for AGS-Ⅳ (r=0.9992). The intra-and inter-day assay variability values were less than 6% and 8%, respectively. Extraction recoveries from plasma were 92.8%-98.4% for AGS-Ⅳ and 80.0%-90.9% for digoxin, respectively. The lower limit of quantitation (LLOQ) for AGS-Ⅳ was 0.5 ng/mL. The concentration-time curves of AGS-Ⅳ for each rat were fitted to an open two-compartment model by CAPP program. The pharmacokinetics parameters of AGS-Ⅳ were as following: the elimination half-life (t1/2β), clearance rate (CL), distribution volume at steady state (Vss), and AUC0-∞ were (3.46±0.52) h, (0.47±0.02) L/h, (0.76±0.16) L/kg and (4.27±0.19) μg·mL-1·h, respectively. CONCLUSION: These results show that this method is satisfied for the measurements of pharmacokinetics study for AGS-Ⅳ.

Adenocarcinoma, Clear Cell ; metabolism ; pathology ; surgery ; Alkaline Phosphatase ; metabolism ; Carcinoma, Endometrioid ; metabolism ; pathology ; Diagnosis, Differential ; Endodermal Sinus Tumor ; metabolism ; pathology ; surgery ; Female ; GPI-Linked Proteins ; metabolism ; Glypicans ; metabolism ; Humans ; Isoenzymes ; metabolism ; Keratin-7 ; metabolism ; Liver Neoplasms ; metabolism ; pathology ; secondary ; Middle Aged ; Mucin-1 ; metabolism ; Ovarian Neoplasms ; metabolism ; pathology ; surgery ; alpha-Fetoproteins ; metabolism

BACKGROUND AND OBJECTIVEThe aim of this study is to evaluate diagnostic yield and the safety of endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) in the diagnosis ofbronchogenic carcinoma.

METHODSBetween July, 2009 and February, 2010, 95 patients with mediastinal/hilar lymphadenopathy and/or intrathoracic peritracheal or peribronchial masses previously detected with CT scan underwent EBUS-TBNA. No rapid onsite cytology was performed.

RESULTSIn all 95 patients, 60 cases were newly diagnosed lung cancer through the pathological examination and clinical follow-up certification. In 60 lung cancer cases, 112 samples were obtained from lymph nodes (LNs) and 11 samples were obtained from intrapulmonary lesions. Fifty-eight cases of patients were diagnosed, false negative in 2 cases. Sensitivity and specificity of EBUS-guided TBNA method in distinguishing benign from malignant LNs or thoracic masses were 96.67% and 100%, respectively. There was any major complication in this series, the procedure was uneventful.

CONCLUSIONEBUSTBNA seemed a safe and effective technique in making bronchogenic carcinoma diagnosis for mediastinal/hilar LNs and intra-pulmonary masses.

Adult ; Aged ; Aged, 80 and over ; Biopsy, Fine-Needle ; methods ; Bronchi ; diagnostic imaging ; pathology ; Carcinoma, Bronchogenic ; diagnosis ; Endosonography ; methods ; Female ; Humans ; Lung Neoplasms ; diagnosis ; Male ; Middle Aged

BACKGROUND:Disseminated intravascular coagulation(DIC)is associated with increased mortality in sepsis patients.In this study,we aimed to assess the clinical ability of sepsis-induced coagulopathy(SIC)and sepsis-associated coagulopathy(SAC)criteria in identifying overt-DIC and pre-DIC status in sepsis patients. METHODS:Data from 419 sepsis patients were retrospectively collected from July 2018 to December 2022.The performances of the SIC and SAC were assessed to identify overt-DIC on days 1,3,7,or 14.The SIC status or SIC score on day 1,the SAC status or SAC score on day 1,and the sum of the SIC or SAC scores on days 1 and 3 were compared in terms of their ability to identify pre-DIC.The SIC or SAC status on day 1 was evaluated as a pre-DIC indicator for anticoagulant initiation. RESULTS:On day 1,the incidences of coagulopathy according to overt-DIC,SIC and SAC criteria were 11.7％,22.0％and 31.5％,respectively.The specificity of SIC for identifying overt-DIC was significantly higher than that of the SAC criteria from day 1 to day 14(P＜0.05).On day 1,the SIC score with a cut-off value＞3 had a significantly higher sensitivity(72.00％)and area under the curve(AUC)(0.69)in identifying pre-DIC than did the SIC or SAC status(sensitivity:SIC status 44.00％,SAC status 52.00％;AUC:SIC status 0.62,SAC status 0.61).The sum of the SIC scores on days 1 and 3 had a higher AUC value for identifying the pre-DIC state than that of SAC(0.79 vs.0.69,P＜0.001).Favorable effects of anticoagulant therapy were observed in SIC(adjusted hazard ratio[HR]=0.216,95％confidence interval[95％CI]:0.060-0.783,P=0.018)and SAC(adjusted HR=0.146,95％CI:0.041-0.513,P=0.003). CONCLUSION:The SIC and SAC seem to be valuable for predicting overt-DIC.The sum of SIC scores on days 1 and 3 has the potential to help identify pre-DIC.

AIM:We investigated how AT 1-R stimulated by mechanical stresses induces cardiac fibrosis .METHODS:We produced in vivo cardiac pressure overload model in angiotensinogen knockout ( ATG-/-) mice and in vitro mechanically-stretched cell model in cultured neonatal cardiac cells of ATG-/-mice both lack the participation of Ang II .RESULTS: Pressure overload for 4 weeks in ATG-/-mice induced myocardial hypertrophy accompanied by the significant interstitial fibrosis , however , the TGF-β, a key regulatory factor of fibrosis, was not significantly increased in these ATG-/-mice.Meanwhile, the inhibitor for AT1-R significantly inhibited mechani-cal stress-induced cardiac fibrosis in these ATG-/-models whereas inhibition of TGF-βdid not.CONCLUSION:The results showed that mechanical stress-induced fibrotic responses through AT 1-R required the phosphorylation of Smad 2 but not the involvement of TGF-β.

Effective supervision of the clinical research management department can guarantee and improve the quality of the investigator initiated trials(IIT). The authors analyzed relevant clinical research regulations and literature and summarized the current situation of risk-based IIT project process quality management. On such basis, they determined the risk-based IIT project process quality management method in combination with the previous research of the research group.From 2021 to 2022, this method was used to implement process quality management for 353 IIT projects in Shanghai′s tertiary hospitals. More than 3 000 risk points were identified through centralized supervision, and then on-site supervision was carried out to correct the problems found. As proven by the results, the method could find existing problems in time and define the risk level of the project, and also formulate an individualized risk supervision plan accordingly, so as to effectively ensure the data reliability and scientific results. It is suggested that the clinical research management department implement risk based management for the whole process of IIT projects, increase funding and staffing, and implement hierarchical management for the projects by research types, so as to promote the sustainable development of IITs.

Objective To explore the correlation between changes in cerebral blood flow and auditory cognitive function in patients with amnestic mild cognitive impairment(aMCI).Methods The aMCI patients who visited the Memory Clinic of Beijing Friendship Hospital from July 2022 to September 2023 were selected as the research subjects,and gender and age matched healthy controls were included in the comparative study.All subjects underwent ASL scans using 3.0 T MRI and underwent a Chinese"repeat-recall"verbal cognitive function test(RRT)as an assessment of auditory cognitive abilities,and the correlation between cerebral blood flow(CBF)changes and auditory cognitive function was finally analyzed.Results A total of 26 patients with aMCI and 32 normal healthy were included.Regardless of the high and low context and signal to noise ratio(SNR),the auditory cognitive ability of the aMCI group significantly decreased compared to the control group(P<0.01).The standardized CBF value of the left inferior parietal lobule in the aMCI group was significantly reduced compared to the control group(0.921±0.234 vs 1.247±0.076,P<0.001).Correlation analysis showed that the standardized CBF value of the left inferior parietal lobule in the aMCI group was correlated with auditory cognitive ability under low contextual conditions of-5 dB signal-to-noise ratio(r=0.857,P<0.001).Conclusion CBF in the left inferior parietal lobe in patients with aMCI may have some relevance for auditory cognitive impairment.

Objective:To understand the clinical characteristics of pregnant women infected with dengue virus (DENV) in Ruili City, Yunnan Province, so as to provide basis for formulating effective diagnosis and treatment protocol of dengue fever in pregnant women.Methods:A total of 18 pregnant women infected with DENV hospitalized in Ruili People's Hospital in 2017 and 2018 were selected as observation group, and 18 non-pregnant women infected with DENV were selected as control group according to the age range of the observation group, and epidemiological and clinical data of patients in the two groups were retrospectively collected. Epidemiological characteristics, clinical symptoms and laboratory biochemical indexes of the two groups were compared and analyzed.Results:There were no significant differences ( t = - 0.032, 0.495, P > 0.05) in age [(27.9 ± 5.3) vs (27.9 ± 5.1) years old] and hospitalization stay [(6.8 ± 1.6) vs (6.6 ± 2.0) d] between the observation group and control group. One pregnant woman in observation group had early pregnancy abortion. Patients of both groups had fever in 18 cases (100.0%), headache, muscle aches, and chills in 14 cases (77.8%), anorexia in 15 cases (83.3%), and nausea and vomiting in 5 cases (27.8%); fatigue in 14 cases (77.8%) and 16 cases (88.9%), respectively; there was 1 case of rash in observation group (5.6%), and no rash in control group. There were no significant differences in the above mentioned clinical symptoms distribution between the two groups ( P > 0.05). On the first day of admission, the reduction proportions in red blood cells [61.1% (11/18) vs 5.6% (1/18)], hemoglobin [50.0% (9/18) vs 16.7% (3/18)], and hematocrit [61.1% (11/18) vs 16.7% (3/18)] in observation group were significantly higher than those in control group ( P < 0.05); on the fifth day of admission, the reduction proportions in hemoglobin [33.3% (6/18) vs 5.6% (1/18)] and hematocrit [33.3% (6/18) vs 5.6% (1/18)] in observation group were significantly higher than those in control group ( P < 0.05). Conclusions:The red blood cells, hemoglobin and hematocrit of pregnant women infected with DENV are significantly reduced, and there is a risk of miscarriage in early pregnancy. It is suggested that relevant departments should strengthen the training of medical staff to diagnose and treat pregnant women infected with DENV early.

Pheretima,also called"earthworms",is a well-known animal-derived traditional Chinese medicine that is extensively used in over 50 Chinese patent medicines(CPMs)in Chinese Pharmacopoeia(2020 edi-tion).However,its zoological origin is unclear,both in the herbal market and CPMs.In this study,a strategy for integrating in-house annotated protein databases constructed from close evolutionary relationship-sourced RNA sequencing data from public archival resources and various sequencing al-gorithms(restricted search,open search,and de novo)was developed to characterize the phenotype of natural peptides of three major commercial species of Pheretima,including Pheretima aspergillum(PA),Pheretima vulgaris(PV),and Metaphire magna(MM).We identified 10,477 natural peptides in the PA,7,451 in PV,and 5,896 in MM samples.Five specific signature peptides were screened and then validated using synthetic peptides;these demonstrated robust specificity for the authentication of PA,PV,and MM.Finally,all marker peptides were successfully applied to identify the zoological origins of Brain Heart capsules and Xiaohuoluo pills,revealing the inconsistent Pheretima species used in these CPMs.In conclusion,our integrated strategy could be used for the in-depth characterization of natural peptides of other animal-derived traditional Chinese medicines,especially non-model species with poorly annotated protein databases.

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.