OBJECTIVE To screen the potential active components of Polygonum orientale flower against myocardial ischemia- reperfusion injury （MIRI） in rats based on physiological and pathological states. METHODS SD rats were divided into normal control group， normal administration group， MIRI control group and MIRI administration group， with 5 rats in each group. After drug intervention or modeling and drug intervention， chromatographic separation plasma samples were collected， and chromatographic separation and mass spectrometry data collection were performed by using UPLC-Q-TOF/MS. The prototype components and metabolites were analyzed by comparing the reference substance maps， the maps of each plasma sample， and the relevant literature. At the same time， the common peaks in plasma samples of rats in normal administration group and MIRI administration group were identified. Combined with principal component analysis and orthogonal partial least square-discriminant analysis， the differential transitional components were screened out according to the value of variable importance in the projection （VIP）＞1， to speculate the potential active components of P. orientale flower in rats under physiological and pathological states. The SD rats were divided into control group， MIRI group， positive control group （Compound danshen tablets 0.2 g/kg， 3 times a day）， and potentially active compound groups （10 mg/kg， twice a day）， with 5 rats in each group. The rats in administration groups were given relevant medicine intragastrically， for 3 consecutive days. The activity of superoxide dismutase （SOD）， the leakages of lactate dehydrogenase （LDH）， creatine kinase isoenzyme-MB （CK-MB） and cardiac troponin Ⅰ （cTnⅠ） in plasma were detected after the last administration. RESULTS Twenty-six main chromatographic peaks were obtained from the total ion chromatogram of the extract of P. orientale flower， and 14 of them were determined， including gallic acid， catechin， protocatechuic acid and so on. There were fifteen （including 6 absorbed prototype components and 9 metabolites） and nineteen transitional components （including 6 absorbed prototype components and 13 metabolites） in the plasma sample of normal rats and MIRI rats. Eight transitional components were detected in both normal rats and MIRI rats， and the VIP values of kaempferol glucuronidation metabolites， quercetin carbonylation metabolites and N-p-paprazine to the corresponding peak were higher than 1. Compared with MIRI group， the activities of SOD were increased significantly in the plasma of MIRI rats in each potential active compound group （P＜0.01）， and the leakages of LDH， CK-MB， and cTnⅠ in the plasma of MIRI rats were reduced significantly （P＜0.01）. CONCLUSIONS The potential anti-MIRI active components in extract of P. orientale flower are N-p-paprazine， quercetin， kaempferol and kaempferol-3-O-β-D-glucoside.

Objective:To investigate the relationship and assess the value of serum polyadenosine diphosphate ribose polymerase 1 (PARP1) and forkhead box transcription factor O1 (FOXO1) with cerebral neurological function in patients with severe craniocerebral injury (SCI).Methods:The clinical data of 100 patients with SCI from February 2021 to October 2022 in Baoji High-Tech Hospital were retrospectively analyzed. The Glasgow coma score (GCS) on admission was recorded. According to the modified Rankin score (mRS) 3 months after discharge, the patients were divided into good recovery group (mRS 0 to 2 scores, 62 cases) and poor recovery group (mRS 3 to 5 scores, 38 cases). In addition, 50 individuals who underwent physical examinations in Baoji High-Tech Hospital during the same period were selected as the control group. The serum levels of PARP1 and FOXO1 were measured by enzyme-linked immunosorbent assay. Correlation analysis was performed using Spearman method. Multifactor Logistic regression was used to analyze the independent risk factors for poor cerebral neurological recovery in patients with SCI. The efficacy of PARP1 and FOXO1 in predicting the poor cerebral neurological recovery in patients with SCI was evaluated by the receiver operating characteristic (ROC) curve.Results:The PARP1 and FOXO1 in good recovery group and poor recovery group were significantly higher than those in control group: (4.14 ± 1.19) and (5.98 ± 1.02) μg/L vs. (2.13 ± 0.71) μg/L, (5.83 ± 1.22) and (7.57 ± 3.12) μg/L vs. (4.23 ± 1.34) μg/L, the indexes in poor recovery group were significantly higher than those in good recovery group, and there were statistical differences ( P<0.05). The mRS in poor recovery group was significantly higher than that in good recovery group: (3.92 ± 0.87) scores vs. (1.03 ± 0.80) scores, and there was statistical difference ( P<0.05). Spearman correlation analysis result showed that PARP1 and FOXO1 were positively correlated with mRS score in patients with SCI ( r = 0.673 and 0.646, P<0.05). Multifactor Logistic regression analysis result showed that the GCS, mRS, PARP1 and FOXO1 were independent risk factors for poor neurological recovery in patients with SCI ( HR = 1.039, 1.286, 1.439 and 1.389; 95% CI 1.003 to 1.076, 1.011 to 1.637, 1.029 to 2.012 and 1.009 to 1.912; P<0.05). ROC curve analysis result showed that the area under the curve (AUC) of PARP1 combination with FOXO1 in assessing poor cerebral neurological recovery in patients with SCI was significantly greater than the PARP1 and FOXO1 alone: 0.953 (95% CI 0.918 to 0.988) vs. 0.866 (95% CI 0.796 to 0.936) and 0.859 (95% CI 0.783 to 0.935), Z = 2.162 and 2.188, P = 0.031 and 0.029. Conclusions:The serum PARP1 and FOXO1 levels in patients with SCI are positively correlated with cerebral neurological recovery, and they have predictive value for cerebral neurological recovery status.

Objective: Comparative analyses of wild-type Clostridioides difficile 630 (Cd630) strain and pathogenicity locus (PaLoc) knockout mutant (ΔPaLoc) by using RNA-seq technology. Analysis of differential expression of Cd630 wild-type strain and ΔPaLoc mutant strain and measurement of its cellular virulence changes. Lay the foundation for the construction of an toxin-attenuated vaccine strain against Clostridioides difficile. Methods: Analysis of Cd630 and ΔPaLoc mutant strains using high-throughput sequencing (RNA-seq). Clustering differentially expressed genes and screening differentially expressed genes by DESeq software. Further analysis of differential genes using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment. Finally, cytotoxicity assays of ΔPaLoc and Cd630 strains were performed in the African monkey kidney epithelial cell (Vero) and the human colonic cell (Caco-2) lines. Results: The transcriptome data showed that the ΔPaLoc mutant toxin genes tcdA and tcdB were not transcribed. Compared to the wild-type strain, CD630_36010, CD630_020910,CD630_02080 and cel genes upregulated 17.92,11.40,8.93 and 7.55 fold, respectively. Whereas the hom2 (high serine dehydrogenase), the CD630_15810 (spore-forming protein), CD630_23230 (zinc-binding dehydrogenase) and CD630_23240 (galactitol 1-phosphate 5-dehydrogenase) genes were down-regulated by 0.06, 0.075, 0.133 and 0.183 fold, respectively. The GO and KEGG enrichment analyses showed that the differentially transcribed genes in ΔPaLoc were enriched in the density-sensing system, ABC transport system, two-component system, phosphotransferase (PTS) system, and sugar metabolism pathway, as well as vancomycin resistance-related pathways. Cytotoxicity assays showed that the ΔPaLoc mutant strain lost its virulence to Vero and Caco-2 cells compared to the wild-type Cd630 strain. Conclusion: Transcriptional sequencing analysis of the Cd630 and ΔPaLoc mutant strains showed that the toxin genes were not transcribed. Those other differential genes could provide a reference for further studies on the physiological and biochemical properties of the ΔPaLoc mutant strain. Cytotoxicity assays confirmed that the ΔPaLoc mutant lost virulence to Vero and Caco-2 cells, thus laying the foundation for constructing an toxin-attenuated vaccine strain against C. difficile.
Bacterial Proteins/metabolism* ; Bacterial Toxins/metabolism* ; Caco-2 Cells ; Clostridioides ; Clostridioides difficile/genetics* ; Humans ; Oxidoreductases/metabolism* ; Transcriptome ; Vaccines, Attenuated

Monoacylglycerol lipase (MAGL) is a pivotal enzyme in the endocannabinoid system, which metabolizes 2-arachidonoylglycerol (2-AG) into the proinflammatory eicosanoid precursor arachidonic acid (AA). MAGL and other endogenous cannabinoid (EC) degrading enzymes are involved in the fibrogenic signaling pathways that induce hepatic stellate cell (HSC) activation and ECM accumulation during chronic liver disease. Our group recently developed an ¹⁸F-labeled MAGL inhibitor ([¹⁸F]MAGL-4-11) for PET imaging and demonstrated highly specific binding in vitro and in vivo. In this study, we determined [¹⁸F]MAGL-4-11 PET enabled imaging MAGL levels in the bile duct ligation (BDL) and carbon tetrachloride (CCl₄) models of liver cirrhosis; we also assessed the hepatic gene expression of the enzymes involved with EC system including MAGL, NAPE-PLD, FAAH and DAGL that as a function of disease severity in these models; [¹⁸F]MAGL-4-11 autoradiography was performed to assess tracer binding in frozen liver sections both in animal and human. [¹⁸F]MAGL-4-11 demonstrated reduced PET signals in early stages of fibrosis and further significantly decreased with disease progression compared with control mice. We confirmed MAGL and FAAH expression decreases with fibrosis severity, while its levels in normal liver tissue are high; in contrast, the EC synthetic enzymes NAPE-PLD and DAGL are enhanced in these different fibrosis models. In vitro autoradiography further supported that [¹⁸F]MAGL-4-11 bound specifically to MAGL in both animal and human fibrotic liver tissues. Our PET ligand [¹⁸F]MAGL-4-11 shows excellent sensitivity and specificity for MAGL visualization in vivo and accurately reflects the histological stages of liver fibrosis in preclinical models and human liver tissues.

Objective:To learn about the status of iodine deficiency disorders (IDD) and iodine nutrition of residents in Shanxi Province since the implementation of the standard of "Iodine Content in Edible Salt" (GB 26878-2011), to evaluate the level of prevention and control of IDD, and to provide scientific basis for adjusting prevention and control strategies.Methods:The data of core indicators monitored by Shanxi Province in accordance with the requirements of the national iodized salt and IDD monitoring program for each year from 2012 to 2021 were comprehensively reviewed, and the change trends of the indicators such as coverage rate of iodized salt, consumption rate of qualified iodized salt, children's median urinary iodine and goiter rate, and pregnant women's median urinary iodine were analyzed; the evaluation of IDD elimination in counties (cities and districts, hereinafter referred to as counties) was analyzed.Results:From 2012 to 2021, the coverage rate of iodized salt in Shanxi Province was remained > 95%; from 2012 to 2014 (transition period between new and old standard iodized salt), the consumption rate of qualified iodized salt had an upward trend (χ 2trend = 2 703.32, P < 0.001), with a downward trend from 2015 to 2017 (before and after the reform of the salt industry system, χ 2trend = 122.18, P < 0.001), and with an upward trend from 2018 to 2021 (after the reform of the salt industry system, χ 2trend = 455.11, P < 0.001), from 2018, the consumption rate of qualified iodized salt remained > 90%; from 2015 to 2021, the average content of salt iodine was between 23 - 25 mg/kg, and the coefficient of variation of salt iodine was 15% - 18%. From 2014 to 2021, the median urinary iodine of children in Shanxi Province remained at 200 - 250 μg/L, the median urinary iodine of pregnant women remained at 150 - 200 μg/L, and the goiter rate of children remained below 5%. Every year, iodine nutrition of pregnant women in some counties was insufficient. In 2016, the proportion of counties with insufficient iodine nutrition of pregnant women was high, reached 30.0% (12/40); from 2018 to 2021, the proportion of counties with insufficient iodine nutrition of pregnant women had a downward trend (χ 2trend = 9.37, P = 0.002), which was 11.1% (13/117) in 2021. In 2020, 117 counties in the province reached the IDD elimination standard, with a compliance rate of 100.0%. Conclusions:Since the implementation of the current salt iodine content standard for 10 years, the consumption rate of qualified iodized salt has gradually stabilized and remained at a high level, which can ensure that IDD is in a sustainable state of elimination in Shanxi Province, and the iodine nutrition of school-age children and pregnant women is generally at a suitable level. However, there are a certain number of counties with insufficient iodine nutrition of pregnant women. It is recommended to guide pregnant women to supplement iodine or set the average standard of salt iodine for pregnant women separately.

As a serine hydrolase, monoacylglycerol lipase (MAGL) is principally responsible for the metabolism of 2-arachidonoylglycerol (2-AG) in the central nervous system (CNS), leading to the formation of arachidonic acid (AA). Dysfunction of MAGL has been associated with multiple CNS disorders and symptoms, including neuroinflammation, cognitive impairment, epileptogenesis, nociception and neurodegenerative diseases. Inhibition of MAGL provides a promising therapeutic direction for the treatment of these conditions, and a MAGL positron emission tomography (PET) probe would greatly facilitate preclinical and clinical development of MAGL inhibitors. Herein, we design and synthesize a small library of fluoropyridyl-containing MAGL inhibitor candidates. Pharmacological evaluation of these candidates by activity-based protein profiling identified

Objective:To discuss the clinical characteristics of the Pneumocystis jirovecii pneumonia (PCP) in the non-HIV-infected blood disease patients, and to analyze its risk factors, treatment methods, prognosis and prevention measures.Methods:A female patient aged 18years old was confirmed as acute myeloid leukemia (AML) , and experienced dyspnea, chest congestion and hypoxaemia during the recovery period of hemogram after chemotherapy.The chest CT showed the bilateral lung diffuse ground glass density images.The patient had a dry cough and the oxygen saturation was gradually decreased to 75％5dafter antibacteriological treatment.A repeat chest CT showed enlarged diffuse ground glass density images on both lungs.Considering about the possibility of PCP, the patient received oral trimethoprim/sulfamethoxazole (TMP/SMX) 1g, once every 6h, in combination with caspofungin.Results:Two days later, the symptoms of the patients were not improved.The patient was transferred to ICU and was diagnosed PCP by bronchoalveolar lavage.The patient was switched to oral TMP/SMX2g, once every 8h, in combination with caspofungin.Meanwhile, the patient received bi-level positive airway pressure ventilation (Bipap) for the increased work of breathing.Five days later, the symptoms of the patients were improved and the Bipap was stopped.The patient got better and discharged 5dlater.The patient continuely received oral TMP/SMX 2g, once every 8hfor 36d.Conclusion:Prevention of PCP should be focused, in the non-HIV-infected blood disease patients receiving chemotherapy.Diagnosis of PCP should be considered in these patients without prevention who once have suspected clinical manifestation of PCP in non-granulocytic phase.Early empirical treatment of PCP and ICU management in the non-HIV-infected blood disease patients with acute respiratory failure are the keys to reduce death and improve the prognosis of PCP.

Objective: To evaluate the prognostic significance of early phase full donor chimerism (FDC) after myeloablative allogeneic peripheral blood stem cell transplantation (allo-PBSCT). Methods: The clinical data of 72 hematological patients received myeloablative allo-PBSCT from Feb. 2016 to Jul. 2017 were analyzed retrospectively. The median age was 36.5 years (range 4-59), 44 were males and 28 females. Of the donors, there were 35 HLA matched sibling donors, 27 haploidentical donors and 10 unrelated donors. Polymerase chain reaction amplification of short tandem repeat sequence (PCR-STR) was used to detect donor cell chimerism (DC) rate of recipient bone marrow at one, two and three months after transplantation. Results: The median follow-up was 462 d (range: 47-805 d), 55 cases were still alive, and 45 cases were disease-free survival (DFS) at the end of follow-up. The 2-year overall survival (OS) and DFS were (68.9±7.7)% and (59.5±6.3)%, respectively. A number of 16 cases underwent relapses, with 2-year cumulative incidence of (24.1±5.3)%. The median time of recurrence was 157(32-374) d. Forty cases (55.6%) developed acute graft-versus-host diseases (aGVHD), with median time of 35.5 (13-90) d. Chronic GVHD (cGVHD) occurred in 23 patients (31.9%), with median time of 169 (94-475) d. Univariate analysis found the following factors were not related to OS, DFS or relapse rate (RR), including age, sex, blood type and sex of donor-recipient, occurrence of aGVHD and cGVHD. The OS and DFS in cases reached FDC and no FDC at two months after transplantation were (85.2±6.9)% vs (66.1±7.7)% (P=0.051) and (76.7±7.7)% vs (48.9±8.1)% (P=0.021), respectively. The RR rate in FDC group was lower than that in no FDC group [(16.6±6.8)% vs (30.4±7.8)%, P=0.187, respectively]. Conclusion The present study confirmed the important value for predicting the prognosis with whether or not the patients reached FDC at the early phase after allo-PBSCT. The OS and DFS in cases with FDC at two months after transplantation were significantly higher than those of no FDC patients.

Objective To understand the distribution of water iodine in the external environment of Shanxi Province, and to provide a basis for redefining and implementation of scientific iodine supplementation in iodine deficiency, iodine adequate or iodine high areas. Methods In 2012 - 2016, administrative villages (neighborhood committees)in 119 counties(cities,districts)in 11 cities of Shanxi Province were selected as the investigation units, and 1 to 5 drinking water samples were collected. Water iodine content was detected using arsenic-cerium catalytic spectrophotometry. Areas standard was designated: water iodine content < 10 μg/L as iodine deficiency areas, > 100 μg/L as iodine high areas. Results A total of 26 213 administrative villages (neighborhood committees) of 1 362 townships (towns) of 119 counties (cities, districts) were surveyed, covering 2 850.94 ten thousand people. A total of 32 766 water samples were collected and the median iodine was 5.2 μg/L. There were 18 199 villages with water iodine < 10 μg/L, accounting for 69.4% (covering 1 812.17 ten thousand people, accounting for 63.6%), 6 471 villages with water iodine 10-<50 μg/L,accounting for 24.7%(covering 787.44 ten thousand people,accounting for 27.6 %),1 166 villages with water iodine 50 - < 100 μg/L,accounting for 4.4% (covering 181.46 ten thousand people, accounting for 6.4%), 377 villages with water iodine ≥100 μg/L, accounting for 1.4%(covering 69.87 ten thousand people, accounting for 2.5%).In 1 362 townships (towns), 71.1% (969)water iodine median was<10 μg/L,24.2%(330)water iodine median was in 10-<50 μg/L,3.4%(46)water iodine median was in 50-<100 μg/L,and 1.2%(17) water iodine median was ≥100 μg/L. In 119 counties(cities,districts),there were 90 counties(accounting for 75.6%) with the water median < 10 μg/L, there were 26 counties (accounting for 21.8%) with the water median 10 - < 50 μg/L. Conclusions Most parts of Shanxi Province(or the resident population) are iodine deficiency areas, the external environment water iodine contents in the rest of the regions are different, we should adopt different iodine supplement or iodine reduction measures in regions with different water iodine levels.

Objective: To analyze the incidence and microbiological features of blood stream infections (BSI) of patients with hematopoietic stem cell transplantation (HSCT) and to provide laboratory data for empirical use of antibiotic for the HSCT patients with BSI. Methods: The incidence of bloodstream infection, the positive rate of blood culture, bacterial spectrum and drug resistance were analyzed in 1 265 HSCT recipients during 2013 and 2015 were retrospectively studied. Results: Of 1265 patients undergoing HSCT, 1 422 cases of suspected BSI occurred in 784 patients (61.98%) , and 464 patients (59.2%) were in the stage of agranulocytosis (ANC<0.5×10⁹/L) . The detection rate of pathogens in 2013-2015 was about 20% and increase year after year. Of the 401 strains detected, 221 were Gram-negative (G^-) bacteria (55.1%) , 165 Gram-positive (G⁺) bacteria (41.2%) and 15 fungi (3.7%) . Escherichia coli (16.0%) , Staphylococcus epidermidis (15.5%) and Klebsiella pneumoniae (11.2%) were listed the top three. The proportion of multidrug resistant Acinetobacter Bauman and Stenotrophomonas maltophilia was 64.70% and 63.64% respectively, and methicillin resistant Staphylococcus aureus (MRSA) was more than half (57.14%) . The ratio of vancomycin resistant Enterococci (VRE) and carbapenem resistant Enterobacteriaceae (CRE) was 14.29% and 6.78% respectively. More than 40% Enterobacteriaceae bacteria were resistant to three or four generation cephalosporin antibiotics, and less were resistant to the carbapenems (6.4%) . However, many non-fermentating bacteria were highly resistant to these antibiotics and showed diversity among different strains, with a rate of 47.8% resistance to carbapenems. All the Staphylococcus were sensitive to vancomycin, teicoplanin and linezolid. Conclusions The incidence of BSI in patients with HSCT was high, and the pathogens were mainly G^- bacteria. In addition to Enterobacteriaceae, the proportion of non-fermentative bacteria was quite high. No Staphylococcus detected were resistant to vancomycin, teicoplanin and linezolid.