Objective To investigate the effects of Simo decoction on duodenal microinflammation and NOD-like receptor thermal protein domain associated protein 3(NLRP3)/cysteinyl aspartate-specific proteinase-1(Caspase-1)/gasdermin D(GSDMD)signaling pathway in rats with functional dyspepsia(FD).Methods The FD model was established by multifactorial method.SD rats were randomly divided into normal group,model group(FD model),positive control group(gavage administration of 0.305 mg·kg-1 mosapride injection)and experimental-H,-M,-L groups(gavage administration of 5.62,2.81,1.40 g·kg-1 Simo decoction).Small intestinal advancement rate and gastric emptying rate was determined;the levels of interleukin(IL)-1 β and IL-18 in serum were determined by enzyme linked immunosorbent assay(ELISA);the protein expression of NLRP3 and GSDMD in duodenal tissue was detected by Western blotting.Results The gastric emptying rates of normal,model,positive control and experimental-H,-M,-Lgroupswere(58.34±5.72)％,(29.16±8.37)％,(48.77±6.10)％,(48.35±6.04)％,(48.20±3.49)％and(39.24±4.20)％;the small intestinal propulsion rates were(82.01±7.55)％,(41.95±9.53)％,(64.61±10.18)％,(75.04±9.76)％,(60.58±7.13)％and(45.89±7.40)％;serum IL-1 β expression were(12.86±0.88),(43.73±4.60),(18.84±0.86),(24.61±1.57),(19.14±0.77)and(29.04±0.72)pg·mL-1;IL-18 expressions were(95.00±3.74),(170.60±8.78),(108.50±3.05),(118.90±3.45),(99.90±8.70)and(141.00±3.71)pg·mL-1;the relative expression levels of NLRP3 proteins were 0.32±0.02,0.84±0.05,0.42±0.03,0.48±0.02,0.61±0.04 and 0.62±0.05;the relative expression levels of GSDMD proteins were 0.34±0.05,0.93±0.06,0.35±0.03,0.52±0.02,0.53±0.06 and 0.55±0.05,respectively.Compared with the normal group,the above indexes in the model group have statistical significance;compared with the model group,the above indexes in the experimental-H group and the positive control group also have statistical significance(P＜0.01 or P＜0.05).Conclusion Simo decoction can effectively improve the general condition and duodenal microinflammation in FD rats,and the mechanism may be related to the inhibition of duodenal NLRP3/Caspase-1/GSDMD signaling pathway.

italic>Artemisia argyi is a traditional Chinese medicine in China, which is used as medicine with its leaves. The leaves of A. argyi mainly contain flavonoids, phenolic acids, volatile oils and other compounds, and have a variety of pharmacological activities. AP2/ERF transcription factors are abundant in plants and are mainly involved in plant growth and development, abiotic stress response and secondary metabolite biosynthesis regulation. However, there are few reports on the AP2/ERF gene family and its functions in A. argyi. In this study, we systematically identified the AP2/ERF gene family in A. argyi genome, and analyzed its phylogenetic tree, protein physicochemical properties, subcellular localization, conserved motifs, promoter elements, and expression patterns. The results showed that a total of 204 AP2/ERF transcription factors were identified in A. argyi genome, encoding proteins consisting of 88-483 amino acids with a relative molecular mass of 10-52.94 kDa and a theoretical isoelectric point of 4.62-9.88. Subcellular prediction showed that the majority of AP2/ERFs were located in the nucleus, cytoplasm, and the minority of them is located in the membrane and chloroplasts. According to the Arabidopsis AP2/ERF family classification, A. argyi AP2/ERF proteins were divided into four subfamilies: Soloist, AP2, ERF (B3, B4, B5, B6), and DREB (A1, A2, A4, A5, A6), among which DREB family accounted for the largest proportion, and the same subfamily had similar conserved motifs. cis-Acting element analysis showed that AP2/ERF promoters have a large number of elements responding to light and abiotic stress. Expression pattern analysis showed that most of the genes of the AP2/ERF family were dominantly expressed mainly in roots and stems, of which 19 were dominantly expressed in leaves, 77 would be induced to be expressed by methyl jasmonate, of which 16 genes were both dominantly expressed in leaves and induced to be expressed by methyl jasmonate, and these AP2/ERF genes may be the key regulatory genes for the synthesis of active ingredients in A. argyi leaves.This study lays the foundation for the functional study of AP2/ERF family genes and their regulating roles in the active components biosynthesis in A. argyi leaves.

Objective To construct and identify an organoid model of human placental site trophoblastic tumor(PSTT).Methods The tumor cells were obtained by digesting and separating the PSTT tissues and then embedded in Matrigel.The organoids were cultured in the specific organoid medium.The histological morphology of the organoid model was observed by HE staining and the expression levels of the PSTT specific markers[human placental prolactin(HPL),human leukocyte antigen-G(HLA-G)and placental alkaline phosphatase(PLAP)]were detected by immunohistochemistry and immunofluorescence,so as to evaluate the consistency between the organoid model and the PSTT tissue.Meanwhile,the morphology and forming efficiency of the constructed model were observed under a microscope after primary culture,passage generation and cryopreservation to evaluate its potential application as an organoid model in basic and clinical translational research of PSTT.Results The constructed organoid model could proliferate stably,growing from small microspheres into compact solid spheres or spheres with follicle-like structures,and could passage after fully grown in 7-10 days.The cell state remained stable after passage,frozen storage and recovery.HE staining showed that the morphology of the cells in the organoids was similar to that of the primary PSTT tumor cells,and immunofluorescence staining showed that the organoids highly expressed HLA-G and lowly expressed β-HCG,indicating that the constructed organoid model mainly contained intermediate trophoblast.Conclusion The adult-derived PSTT organoid(ADPO)models were successfully established.

Objective: To investigate the association of plasma vitamin B₁₂ level with plasma uric acid level among the elderly over 65 in 9 longevity areas of China. Methods: The elderly over 65 years old with complete information on plasma vitamin B₁₂ and plasma uric acid from Healthy Aging and Biomarkers Cohort Study (2017 to 2018) were recruited in this study. Information on socio-demographic characteristics, life styles, diet intake, and health status were collected by questionnaire and physical examination; and fasting venous blood was collected to detect the levels of plasma vitamin B₁₂, uric acid and other indicators. Multiple linear regression models were used to analyze the association of plasma vitamin B₁₂ level per interquartile range increase with plasma uric acid level. The association trend of plasma vitamin B₁₂ level with plasma uric acid level was described by restrictive cubic splines fitting multiple linear regression model. Multiple logistic regression models were used to analyze the association of plasma vitamin B₁₂ level stratified by quartiles with hyperuricemia. Results: A total of 2 471 participants were finally included in the study, the age was (84.88±19.76) years old, of which 1 291 (52.25%) were female. The M (Q₁, Q₃) level of plasma vitamin B₁₂ was 294 (203, 440) pg/ml and the plasma uric acid level was (341.01±90.46) μmol/L. A total of 422 participants (17.08%) were defined with hyperuricemia. The results of multiple linear regression model showed that there was a positive association of plasma vitamin B₁₂ level with plasma uric acid level after adjustment for covariates (P<0.05). An IQR increase in plasma vitamin B₁₂ (237 pg/ml) was associated with a 6.36 (95%CI: 2.00-10.72) μmol/L increase in the plasma uric acid level. The restrictive cubic splines curve showed a positive linear association of log-transformed plasma vitamin B₁₂ with uric acid level (P<0.001). Conclusion: There is a positive association of plasma vitamin B₁₂ level with plasma uric acid level among the elderly over 65 years old in 9 longevity areas of China.
Humans ; Female ; Aged ; Aged, 80 and over ; Male ; Vitamin B 12 ; Uric Acid ; Cohort Studies ; Hyperuricemia ; Vitamins ; Folic Acid

Objective: To identify the main metals involved in cognitive impairment in the Chinese oldest old, and explore the association between these metal exposures and cognitive impairment. Methods: A cross-sectional study was conducted on 1 568 participants aged 80 years and older from Healthy Aging and Biomarkers Cohort Study (2017 to 2018). Fasting venous blood was collected to measure the levels of nine metals (selenium, lead, cadmium, arsenic, antimony, chromium, manganese, mercury, and nickel). The cognitive function of these participants was evaluated by using the Chinese version of the Mini-Mental State Examination (CMMSE). The random forest (RF) was applied to independently identify the main metals that affected cognitive impairment. The multivariate logistic regression model and restricted cubic splines (RCS) model were used to further verify the association of the main metals with cognitive impairment. Results: The age of 1 568 study subjects was (91.8±7.6) years old, including 912 females (58.2%) and 465 individuals (29.7%) with cognitive function impairment. Based on the RF model (the out-of-bag error rate was 22.9%), the importance ranking of variables was conducted and the feature screening of five times ten-fold cross-validation was carried out. It was found that selenium was the metal that affected cognitive function impairment, and the other eight metals were not included in the model. After adjusting for covariates, the multivariate logistic regression model showed that with every increase of 10 μg/L of blood selenium levels, the risk of cognitive impairment decreased (OR=0.921, 95%CI: 0.889-0.954). Compared with the lowest quartile(Q₁) of blood selenium, the ORs (95%CI) of Q₃ and Q₄ blood selenium were 0.452 (0.304-0.669) and 0.419 (0.281-0.622) respectively. The RCS showed a linear dose-response relationship between blood selenium and cognitive impairment (P_nonlinear>0.05). Conclusion: Blood selenium is negatively associated with cognitive impairment in the Chinese oldest old.
Aged, 80 and over ; Female ; Humans ; Selenium ; Cohort Studies ; Cross-Sectional Studies ; Metals/analysis* ; Cognitive Dysfunction/epidemiology* ; China/epidemiology*

OBJECTIVE: To report on the clinical, metabolic and genetic characteristics of a child with carnitine palmitoyl transferase 1A (CPT1A) deficiency. METHODS: Clinical data and the level of acylcarnitine for a child who initially presented as epilepsy were analyzed. Genomic DNA was extracted from peripheral blood samples of the child and her parents and subjected to next-generation sequencing (NGS). RESULTS: Mass spectrometry of blood acylcarnitine indicated increased carnitine 0 (C0) and significantly increased C0/ (C16+C18). DNA sequencing revealed that the child has carried compound heterozygous variants of the CPT1A gene, namely c.1846G>A and c.2201T>C, which were respectively inherited from her mother and father. CONCLUSION CPT1A presenting initially as epilepsy was unreported previously. Analysis of blood acylcarnitine C0 and C0/ (C16 + C18) ratio and NGS are necessary for the identification and diagnosis of CPT1A deficiency. The c.1846G>A and c.2201T>C variants of the CPT1A gene probably underlay the disease in this child. Above finding has also enriched the spectrum of CPT1A gene variants.
Carnitine/blood* ; Carnitine O-Palmitoyltransferase/genetics* ; Child ; DNA Mutational Analysis ; Female ; Humans ; Hypoglycemia/genetics* ; Lipid Metabolism, Inborn Errors/genetics*

Aortic Valve/surgery* ; Aortic Valve Stenosis/surgery* ; Heart Valve Prosthesis ; Heart Valve Prosthesis Implantation ; Humans ; Risk Assessment ; Severity of Illness Index

Objective:To evaluate the efficacy of three-dimensional (3D) visualization technology in the precision diagnosis and treatment for primary liver cancer.Methods:A total of 1 665 patients with primary liver cancer who admitted to seven medical centers in China between January 2009 to January 2019, diagnosed and treated by 3D visualization protocol were analyzed, and their clinical data were retrospectively reviewed. There were 1 255 males (75.4%) and 410 females (24.6%) , with age of (52.9±11.9) years (range: 18 to 86 years) .The acquisition of high-quality CT images with submillimeter spatial resolution were conducted using a quality control system. By means of homogenization methods, 3D reconstruction and 3D visualization analysis were performed. Postoperative observation: pathology reports, microvascular invasion, perioperative complications and follow-up. SPSS 25.0 statistical software was used for statistical description and analysis of clinical data.Results:In the sample of 1 265 patients, 3D reconstructed models clearly displayed in follows. (1) tumor size: ≤2 cm in 155 cases (9.31%) , >2 cm to 5 cm in 551 cases (33.09%) , >5 cm to 10 cm in 636 cases (38.20%) , >10 cm in 323 cases (19.40%) . (2) Classification of hepatic blood vessels. Hepatic artery: type Ⅰ (normal type) in 1 494 cases (89.73%) ,variant hepatic artery in 171 cases (10.27%) , including type Ⅱ in 35 cases, type Ⅲ in 38 cases, and other types in 98 cases. Hepatic vein: type Ⅰ (normal) in 1 195 cases (71.77%) ,variant hepatic veins in 470 cases (28.23%) , including type Ⅱ in 376 cases and type Ⅲ in 94 cases. Portal vein: normal type in 1 315 cases (78.98%) ,variant portal veins in 350 cases (21.02%) , including type Ⅰ in 189 cases, type Ⅱin 103 cases, type Ⅲ in 50 cases, type Ⅳ in 8 cases. Hepatic artery variation coexisting with portal vein variation in 24 cases (1.44%) . Hepatic vein variation coexisting with portal vein variation in 113 cases (6.79%) . Three types of vascular variation in 4 cases (0.24%) , including coexistence of type Ⅱ hepatic artery variation or type Ⅰ portal vein variation with type Ⅲ hepatic vein variation in 2 cases,coexistence of type Ⅲ hepatic artery variation or type Ⅲ portal vein variation with type Ⅱ hepatic vein variation in 2 cases. (3) Preoperative liver volume calculation: 1 499.3 (514.4) ml (range: 641.7 to 6 637.0 ml) of total liver volume, including 479.1 (460.1) ml (range:10.5 to 2 086.8 ml) for liver resection and 959.9 (460.4) ml (range:306.1 to 5 638.0 ml) for residual function. (4) Operative methods: anatomical hepatectomy in 1 458 cases (87.57%) ; non-anatomic hepatectomy in 207 cases (12.43%) . (5) the median operation time was 285 (165) minutes (range: 40 to720 minutes) . (6) The median intraoperative blood loss was 200 (250) ml (range:10 to 4 200 ml) and 346 cases (20.78%) had intraoperative transfusion. (7) Pathology reports: hepatocellular carcinoma in 1 371 cases (82.34%) , cholangiocarcinoma in 260 cases (15.62%) and mixed hepatocellular carcinoma in 34 cases (2.04%) . Microvascular invasion: M0 in 199 cases, M1 in 64 cases, and M2 in 27 cases. (8) Postoperative complications in 207 cases (12.43%) , including Clavien-Dindo grade Ⅰ or Ⅱ in 57 cases, grade Ⅲ or Ⅳ in 147 cases and grade Ⅴ in 3 cases.There were 13 cases (0.78%) of liver failure and 3 cases (0.18%) of perioperative death. (9) The follow-up time was 3.0 to 96.0 months, with a median time of 21.0(17.8) years. The overall 3-year survival and disease-free survival rates were 80.0% and 56.5%, respectively. The overall 5-year survival and disease-free survival rates were 59.7% and 30.0%, respectively.Conclusion:3D visualization technology plays an important role in realizing accurate diagnosis of anatomical location and morphology of primary liver cancer, improving the success rate of surgery and reducing the incidence of complications.

Objective:To evaluate the efficacy of three-dimensional(3D) visualization technology in the precision diagnosis and treatment for primary liver cancer.Methods:A total of 1 665 patients with primary liver cancer who admitted to seven medical centers in China between January 2009 to January 2019, diagnosed and treated by 3D visualization protocol were analyzed, and their clinical data were retrospectively reviewed. There were 1 255 males(75.4%) and 410 females(24.6%), with age of (52.9±11.9) years (range: 18 to 86 years). The acquisition of high-quality CT images with submillimeter spatial resolution were conducted using a quality control system. By means of homogenization methods, 3D reconstruction and 3D visualization analysis were performed. Postoperative observation: pathology reports, microvascular invasion, perioperative complications and follow-up. SPSS 25.0 statistical software was used for statistical description and analysis of clinical data. Kaplan-Meier curve was used to calculate overall survival and disease-free survival rate.Results:(1)In the sample of 1 265 patients, 3D reconstructed models clearly displayed as follows. tumor size: ≤2 cm in 155 cases (9.31%), >2 cm to 5 cm in 551 cases (33.09%), >5 cm to 10 cm in 636 cases (38.20%), >10 cm in 323 cases (19.40%). (2) Classification of hepatic blood vessels. Hepatic artery: type Ⅰ(normal type) in 1 494 cases(89.73%),variant hepatic artery in 171 cases (10.27%), including type Ⅱ in 35 cases, type Ⅲ in 38 cases, and other types in 98 cases. Hepatic vein: type Ⅰ (normal) in 1 195 cases (71.77%),variant hepatic veins in 470 cases(28.23%), including type Ⅱ in 376 cases and type Ⅲ in 94 cases. Portal vein:normal type in 1 315 cases (78.98%), variant portal veins in 350 cases (21.02%), including type Ⅰ in 189 cases, type Ⅱin 103 cases, type Ⅲ in 50 cases, type Ⅳ in 8 cases. Hepatic artery variation coexisting with portal vein variation in 24 cases (1.44%). Hepatic vein variation coexisting with portal vein variation in 113 cases (6.79%). Three types of vascular variation in 4 cases (0.24%), including coexistence of type Ⅱ hepatic artery variation or type Ⅰ portal vein variation with type Ⅲ hepatic vein variation in 2 cases,coexistence of type Ⅲ hepatic artery variation or type Ⅲ portal vein variation with type Ⅱ hepatic vein variation in 2 cases. (3) Preoperative liver volume calculation:1 499.3 (514.4)ml (range:641.7 to 6 637.0 ml) of total liver volume, including 479.1 (460.1) ml (range:10.5 to 2 086.8 ml) for liver resection and 959.9 (460.4)ml (range:306.1 to 5 638.0 ml) for residual function. (4)Operative methods: anatomical hepatectomy in 1 458 cases (87.57%); non-anatomic hepatectomy in 207 cases (12.43%). (5)the median operation time was 285(165)minutes (range: 40 to720 minutes). (6)The median intraoperative blood loss was 200(250)ml (range:10 to 4 200 ml) and 346 cases (20.78%) had intraoperative transfusion. (7)Pathology reports: hepatocellular carcinoma in 1 371 cases (82.34%), cholangiocarcinoma in 260 cases (15.62%) and mixed hepatocellular carcinoma in 34 cases (2.04%). Microvascular invasion: M0 in 199 cases, M1 in 64 cases, and M2 in 27 cases. (8)Postoperative complications in 207 cases (12.43%), including Clavien-Dindo grade Ⅰ or Ⅱ in 57 cases, grade Ⅲ or Ⅳ in 147 cases and grade Ⅴ in 3 cases.There were 13 cases (0.78%) of liver failure and 3 cases (0.18%) of perioperative death. (9) The follow-up time was 3.0 to 96.0 months, with a median time of 21.0(17.8) years. The overall 3-year survival and disease-free survival rates were 80.0% and 56.5%, respectively. The overall 5-year survival and disease-free survival rates were 59.7% and 30.0%, respectively.Conclusion:3D visualization technology plays an important role in realizing accurate diagnosis of anatomical location and morphology of primary liver cancer, improving the success rate of surgery and reducing the incidence of complications.

To address the increasing need for detecting and validating protein biomarkers in clinical specimens, mass spectrometry (MS)-based targeted proteomic techniques, including the selected reaction monitoring (SRM), parallel reaction monitoring (PRM), and massively parallel data-independent acquisition (DIA), have been developed. For optimal performance, they require the fragment ion spectra of targeted peptides as prior knowledge. In this report, we describe a MS pipe-line and spectral resource to support targeted proteomics studies for human tissue samples. To build the spectral resource, we integrated common open-source MS computational tools to assemble a freely accessible computational workflow based on Docker. We then applied the workflow to gen-erate DPHL, a comprehensive DIA pan-human library, from 1096 data-dependent acquisition (DDA) MS raw files for 16 types of cancer samples. This extensive spectral resource was then applied to a proteomic study of 17 prostate cancer (PCa) patients. Thereafter, PRM validation was applied to a larger study of 57 PCa patients and the differential expression of three proteins in prostate tumor was validated. As a second application, the DPHL spectral resource was applied to a study consisting of plasma samples from 19 diffuse large B cell lymphoma (DLBCL) patients and 18 healthy control subjects. Differentially expressed proteins between DLBCL patients and healthy control subjects were detected by DIA-MS and confirmed by PRM. These data demonstrate that the DPHL supports DIA and PRM MS pipelines for robust protein biomarker discovery. DPHL is freely accessible at https://www.iprox.org/page/project.html?id=IPX0001400000.