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Autism Spectrum Disorders (ASD) comprise a range of early age-onset neurodevelopment disorders with genetic heterogeneity. Most ASD related genes are involved in synaptic function, which is regulated by mature brain-derived neurotrophic factor (mBDNF) and its precursor proBDNF in a diametrically opposite manner: proBDNF inhibits while mBDNF potentiates synapses. Here we generated a knock-in mouse line (BDNFmet/leu) in which the conversion of proBDNF to mBDNF is attenuated. Biochemical experiments revealed residual mBDNF but excessive proBDNF in the brain. Similar to other ASD mouse models, the BDNFmet/leu mice showed reduced dendritic arborization, altered spines, and impaired synaptic transmission and plasticity in the hippocampus. They also exhibited ASD-like phenotypes, including stereotypical behaviors and deficits in social interaction. Moreover, the plasma proBDNF/mBDNF ratio was significantly increased in ASD patients compared to normal children in a case-control study. Thus, deficits in proBDNF to mBDNF conversion in the brain may contribute to ASD-like behaviors, and plasma proBDNF/mBDNF ratio may be a potential biomarker for ASD.
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Alzheimer's disease (AD) constitutes a neurodegenerative disorder marked by a progressive decline in cognitive function and memory capacity. The accurate diagnosis of this condition predominantly relies on cerebrospinal fluid (CSF) markers, notwithstanding the associated burdens of pain and substantial financial costs endured by patients. This study encompasses subjects exhibiting varying degrees of cognitive impairment, encompassing individuals with subjective cognitive decline, mild cognitive impairment, and dementia, constituting a total sample size of 82 participants. The primary objective of this investigation is to explore the relationships among brain atrophy measurements derived from magnetic resonance imaging, atypical electroencephalography (EEG) patterns, behavioral assessment scales, and amyloid ß-protein (Aß) indicators. The findings of this research reveal that individuals displaying reduced Aß1-42/Aß-40 levels exhibit significant atrophy in the frontotemporal lobe, alongside irregularities in various parameters related to EEG frequency characteristics, signal complexity, inter-regional information exchange, and microstates. The study additionally endeavors to estimate Aß1-42/Aß-40 content through the application of a random forest algorithm, amalgamating structural data, electrophysiological features, and clinical scales, achieving a remarkable predictive precision of 91.6%. In summary, this study proposes a cost-effective methodology for acquiring CSF markers, thereby offering a valuable tool for the early detection of AD.
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Enfermedad de Alzheimer , Péptidos beta-Amiloides , Organoides , Proteínas tau , Enfermedad de Alzheimer/metabolismo , Enfermedad de Alzheimer/patología , Humanos , Proteínas tau/metabolismo , Organoides/metabolismo , Organoides/patología , Péptidos beta-Amiloides/metabolismo , Precursor de Proteína beta-Amiloide/metabolismo , Precursor de Proteína beta-Amiloide/genética , Animales , Encéfalo/metabolismo , Encéfalo/patologíaRESUMEN
One critical manifestation of neurological deterioration is the sign of cognitive decline. Causes of cognitive decline include but are not limited to: aging, cerebrovascular disease, Alzheimer's disease, and trauma. Currently, the primary tool used to examine cognitive decline is scale. However, scale examination has drawbacks such as its clinician subjectivity and inconsistent results. This study attempted to use resting-state EEG to construct a cognitive assessment model that is capable of providing a more scientific and robust evaluation on cognition levels. In this study, 75 healthy subjects, 99 patients with Mild Cognitive Impairment (MCI), and 78 patients with dementia were involved. Their resting-state EEG signals were collected twice, and the recording devices varied. By matching these EEG and traditional scale results, the proposed cognition assessment model was trained based on Adaptive Boosting (AdaBoost) and Support Vector Machines (SVM) methods, mapping subjects' cognitive levels to a 0-100 test score with a mean error of 4.82 (<5%). This study is the first to establish a continuous evaluation model of cognitive decline on a large sample dataset. Its cross-device usability also suggests universality and robustness of this EEG model, offering a more reliable and affordable way to assess cognitive decline for clinical diagnosis and treatment as well. Furthermore, the interpretability of features involved may further contribute to the early diagnosis and superior treatment evaluation of Alzheimer's disease.
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Pulmonary fibrosis is a progressive interstitial fibrotic lung disease with high mortality.Its pathogenesis is complex and involves the reprogramming of fatty acid metabolism.This reprogramming includes changes in de novo fatty acid synthesis,uptake,oxidation,and derivatives.It crucially influences alveolar epithelial cell survival,macrophage polarization,and fibroblast activation,thereby playing a significant role in either exacerbating or miti-gating the disease.Understanding and intervening in the reprogramming of fatty acid metabolism offers potential strategies for prevention,diagnosing and treatment of pulmonary fibrosis.
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Objective To evaluate the clinical application value of matrix-assisted laser desorption ionization time-of-flight mass spectrometry(MALDI-TOF MS)in analyzing the homology of Acinetobacter baumannii(AB).Methods After excluding repetitive strains from multiple specimens of the same patient or environment,a total of 46 AB strains isolated from patients'sputum and environmental specimens of neurological intensive care unit(ICU)in a tertiary first-class general hospital from May 2020 to February 2021 were collected.Strains were detected by VITEK-MS mass spectrometer.Cluster analysis was performed by SARAMIS Premium software,and verified by multilocus sequence typing(MLST).Results Cluster analysis and comparison of MALDI-TOF MS and MLST found that among the 46 AB strains,39 were the type MS-a of MALDI-TOF MS,of which 22 strains were the clus-ter MT-A of MLST,including ST208(n=3),ST540(n=3),ST195(n=8),ST369(n=5),ST136(n=1),ST436(n=1)and ST1893(n=1);16 strains were MT-B,including type ST381(n=4),type ST469(n=11),and type ST938(n=1);one strain was cluster MT-C(ST1821);one strain of type MS-b was ST381;two strains of type MS-c were ST369;one strain of type MS-d was ST195;two strains of type MS-e were ST540 and ST369,respectively;one strain of type MS-f was STN1.Conclusion As a homology analysis method,MALDI-TOF MS still has certain limitations such as low consistency with MLST results,low resolution and specificity,thus cannot replace MLST technology.
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OBJECTIVE To investigate the effects of Taohong siwu decoction modified granules on podocyte epithelial- mesenchymal-transition (EMT) and renal fibrosis in diabetic kidney disease (DKD) model rats. METHODS Eight rats were selected as normal group (ordinary feed); the remaining rats were given a high-glucose and high-fat diet combined with intraperitoneal injection of streptozotocin (35 mg/kg) to induce the DKD model. Model rats were randomly divided into model group, irbesartan group [positive control, 13.5 mg/(kg·d)] and modified Taohong siwu decoction group [6.48 g/(kg·d)], with 8 rats in each group. All groups were given relevant medicine intragastrically, once a day, for 16 consecutive weeks. Twenty-four- hour urinary total protein (24 h UTP) was detected at the end of the 4th, 8th, 12th and 16th week of administration. After the last medication, the body mass, water intake, food intake, urine output, the levels of fasting blood glucose, serum creatinine (Scr) and blood urea nitrogen (BUN) as well as mRNA and protein expressions of P-cadherin, nephrin, α -smooth muscle actin (α-SMA), Wilms’ tumor gene 1 (WT1), transforming growth factor-β1( TGF-β1) and type Ⅳ collagen (Col-Ⅳ) in renal tissue were determined. The pathological and morphological changes in renal tissue were observed and the thickness of the glomerular basement membrane was determined. RESULTS Compared with the model group, 24 h UTP of rats was significantly decreased in modified Taohong siwu decoction group since the 8th weekend (P<0.05); the body weight of rats increased significantly, but the amount of water intake and urine decreased significantly; Scr and BUN level, mRNA expression of α-SMA, mRNA and protein expressions of TGF-β1 and Col-Ⅳ were significantly reduced, while the mRNA expressions of P-cadherin, nephrin and WT1 were increased significantly (P<0.05); the protein deposition of α-SMA was reduced, protein depositions of P-cadherin, nephrin and WT1 were increased; the pathological damage and fibrosis of renal tissue were relieved; the thickness of glomerular basement membrane was decreased significantly (P<0.05). CONCLUSIONS Taohong siwu decoction modified granules can inhibit the EMT of podocyte in DKD model rats, and alleviate renal pathological damage and podocyte damage, thus protecting renal function, and delaying the process of renal fibrosis.
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OBJECTIVE To investigate the effects of Taohong siwu decoction modified granules on podocyte epithelial- mesenchymal-transition (EMT) and renal fibrosis in diabetic kidney disease (DKD) model rats. METHODS Eight rats were selected as normal group (ordinary feed); the remaining rats were given a high-glucose and high-fat diet combined with intraperitoneal injection of streptozotocin (35 mg/kg) to induce the DKD model. Model rats were randomly divided into model group, irbesartan group [positive control, 13.5 mg/(kg·d)] and modified Taohong siwu decoction group [6.48 g/(kg·d)], with 8 rats in each group. All groups were given relevant medicine intragastrically, once a day, for 16 consecutive weeks. Twenty-four- hour urinary total protein (24 h UTP) was detected at the end of the 4th, 8th, 12th and 16th week of administration. After the last medication, the body mass, water intake, food intake, urine output, the levels of fasting blood glucose, serum creatinine (Scr) and blood urea nitrogen (BUN) as well as mRNA and protein expressions of P-cadherin, nephrin, α -smooth muscle actin (α-SMA), Wilms’ tumor gene 1 (WT1), transforming growth factor-β1( TGF-β1) and type Ⅳ collagen (Col-Ⅳ) in renal tissue were determined. The pathological and morphological changes in renal tissue were observed and the thickness of the glomerular basement membrane was determined. RESULTS Compared with the model group, 24 h UTP of rats was significantly decreased in modified Taohong siwu decoction group since the 8th weekend (P<0.05); the body weight of rats increased significantly, but the amount of water intake and urine decreased significantly; Scr and BUN level, mRNA expression of α-SMA, mRNA and protein expressions of TGF-β1 and Col-Ⅳ were significantly reduced, while the mRNA expressions of P-cadherin, nephrin and WT1 were increased significantly (P<0.05); the protein deposition of α-SMA was reduced, protein depositions of P-cadherin, nephrin and WT1 were increased; the pathological damage and fibrosis of renal tissue were relieved; the thickness of glomerular basement membrane was decreased significantly (P<0.05). CONCLUSIONS Taohong siwu decoction modified granules can inhibit the EMT of podocyte in DKD model rats, and alleviate renal pathological damage and podocyte damage, thus protecting renal function, and delaying the process of renal fibrosis.
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Objective:To investigate the application effects of non-invasive ultrasound cardiac output monitoring (USCOM) in fluid resuscitation guidance and hemodynamic evaluation of patients with sepsis.Methods:A total of 80 patients with sepsis who were treated in The Second Hospital of Jiaxing from January 2021 to December 2022 were included in this single-blind randomized controlled study. These patients were randomly divided into a control group ( n = 40) and an observation group ( n = 40). In the control group, continuous cardiac output indicated by pulse waveform monitoring was used to guide fluid resuscitation and monitor hemodynamic status, while in the observation group, USCOM was used to guide fluid resuscitation and monitor hemodynamic status. The fluid intake and outflow at 24, 48, and 72 hours after admission to the ICU were compared between the two groups. The changes in arterial blood lactate and oxygenation index at 1, 2, 3, 5, and 7 days after admission to the ICU were compared between the two groups. The time of admission to ICU, the length of ICU stay, and changes in hemodynamic indicators were compared between the two groups. The incidence of death within 28 days after admission to the ICU was compared between the two groups. Results:The liquid intake and output in the observation group at 24, 48 , and 72 hours after admission to the ICU were (4 178.13 ± 327.19) mL, (7 763.63 ± 324.08) mL, and (10 501.38 ± 376.74) mL, respectively, which were significantly lower than (4 527.35 ± 276.84) mL, (8 778.15 ± 361.42) mL, and (11 589.12 ± 413.27) mL in the control group ( t = 5.15, 13.22, 12.30, all P < 0.001). The arterial blood lactate levels in the observation group were significantly lower than those in the control group at 1, 2, 3, 5, and 7 days ( t = 5.73, 6.73, 9.98, 12.25, 14.47, all P < 0.001). There was no significant difference in oxygenation index between the two groups on the 1 st day ( P > 0.05). The oxygenation index in the observation group at 2, 3, 5 and 7 days was significantly higher than that in the control group ( t = -4.31, -8.19, -5.28, -9.44, all P < 0.05). The time of admission to ICU and the length of ICU stay in the observation group were (10.15 ± 2.43) days and (16.51 ± 1.36) days, respectively, which were significantly shorter than (12.75 ± 2.87) days and (17.68 ± 1.59) days in the control group ( t = 4.37, 3.54, both P < 0.05). After 24 hours of resuscitation, cardiac output, stroke output, and cardiac index in the observation group were (5.89 ± 0.51) L/min, (57.71 ± 3.82) mL, and (3.31 ± 0.35) L·min -1·m -2, respectively, which were significantly higher than (5.30 ± 0.37) L/min, (50.06 ± 3.25) mL, and (2.85 ± 0.34) L·min -1·m -2 in the control group ( t = -5.92, -9.65, -5.96, all P < 0.001). There was no significant difference in the 28-day mortality rate between the two groups ( P > 0.05). Conclusion:The guidance of USCOM on fluid resuscitation and hemodynamic status assessment in sepsis patients has an obvious effect, which can promote the improvement of patient oxygenation index, and shorten the time of admission to the ICU and the length of hospital stay.
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Objective:To investigate the risk factors of invasive fungal disease after haploid hematopoietic stem cell transplantation in children with acute leukemia.Methods:Four hundred and two children (median age 10 years) with acute leukemia, undergoing haplo-HSCT at this institutute from January 2016 to December 2020,were analyzed retrospectively according to the diagnosis criteria of IFD. The basic information and preoperative indicators of the children were collected, including gender, age, primary disease, remission status of primary disease, and previous IFD history. Postoperative indicators were collected, including long-term granulocyte deficiency time, high-dose glucocorticoids, using CD25 monoclonal antibody, acute and chronic graft-versus-host disease. Count data are expressed as example (%), and comparisons between groups are made using the continuously multifactorial corrected Chi-square test or Fisher exact probability method. Logistic regression model was used to analyze the risk factors of IFD after haplo-HSCT in children.Results:Among 402 cases, 250 were male and 152 were female. The median age at transplantation was 10 years, and the age range was 9 months to 17 years 7 months. Before transplantation, 390 cases achieved complete remission of the primary disease, 9 cases had partial remission, and 3 cases had no remission. The implantation time of neutrophils ranged from +10 to 24 days, with a median time of 12 days. IFD occurred in 17 cases (4.2%), of which 3 cases (0.7%) were proven IFD and 14 cases (3.5%) were probable IFD. IFD occurred from 13 to 275 days after transplantation, with a median time of 30 days. The lungs were the most common site of infection (88.2%,15/17). The multivariate Logistic regression analysis showed that age >10 years old ( P=0.046, odds ratio =3.05, 95% confidence interval: 1.02~9.13), the use of high-dose corticosteroids ( P=0.005, odds ratio =7.72, 95% confidence interval: 1.85~32.20) were risk factors for IFD after haplo-HSCT in children. Conclusions:IFD is an important complication after haplo-HSCT in children with acute leukemia. Age >10 years and the use of high-dose corticosteroid are risk factors for IFD after haplo-HSCT in children with acute leukemia.
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Objective:To explore the association between the G71R polymorphism of the UGT1A1 gene and neonatal hyperbilirubinemia. Methods:DNA was extracted from blood samples of 61 neonates with severe neonatal hyperbilirubinemia(severe neonatal hyperbilirubinemia group), 60 neonates with hyperbilirubinemia(hyperbilirubinemia group) and 62 healthy neonates(control group), the G71R mutation of UGT1A1 gene was analyzed by direct sequencing. Results:In severe neonatal hyperbilirubinemia group, there were 17 cases of homozygous mutation(A/A), 23 cases of heterozygous mutation(A/G) , and 21 cases of wild type(G/G) , with 28.87% homozygous mutation rate and 37.70% heterozygous mutation rate.In neonatal hyperbilirubinemia group, there were ten cases of homozygous mutation(A/A), 28 cases of heterozygous mutation(A/G) and 22 cases of wild type(G/G), with 16.67% homozygous mutation rate and 46.67% heterozygous mutation rate.In the control group, there were nine cases of homozygous mutation (A/A), 28 cases of heterozygous mutation(A/G) and 25 cases of wild type(G/G), among which the homozygous mutation rate was 14.52% and the heterozygous mutation rate was 45.16%.The genotype frequency( χ2=4.14, P=0.38)and allele frequency( χ2=2.47, P=0.29)of G71R in severe neonatal hyperbilirubinemia group, neonatal hyperbilirubinemia group and control group were not statistically significant. Conclusion:The G71R polymorphism of the UGT1A1 gene may not be significantly correlated with the prevalence of neonatal hyperbilirubinemia.
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Objective:To preliminarily develop a fertility motivation scale for infertile women (FMS-IW) and test its reliability and validity.Methods:The FMS-IW was developed according to the theory of self-determination and Maslow's hierarchy of needs, and the original item pool was established through clinical psychological counseling practice experience, literature review, consulting clinical psychotherapists, interviewing with infertile women and open-ended questionnaires. The original scale was constructed on item analysis and exploratory factor analysis in 257 infertile women. The formal version of FMS-IW was further adapted by Delphi method and tested in another 392 women to conduct confirmatory factor analysis and reliability test. Furthermore, 56 participants of 392 women were randomly retested with FMS-IW after two weeks.SPSS 25.0 and Amos 24.0 software were used for Spearman analysis, exploratory factor analysis and confirmatory factor analysis.Results:Exploratory factor analysis showed that the FMS-IW was composed of 16 items consisting of two factors: autonomous fertility motivation and controlled fertility motivation. The cumulative variance contribution rate was 64.18%. Confirmatory factor analysis showed that the model fitted well ( χ2/ df=3.292, RMSEA=0.077, SRMR=0.055, GFI=0.902, AGFI=0.871, IFI=0.938, CFI=0.938, TLI=0.928). The Cronbach's α coefficient of the FMS-IW was 0.908. The Cronbach's α coefficient for autonomous and controlled fertility motivation was 0.911 and 0.928, respectively. The parity split-half coefficient of the formal version of FMS-IW was 0.870. The test-retest reliability of the formal version of FMS-IW was 0.823. Conclusion:The FMS-IW has good reliability and validity, and can be used as an effective tool to measure fertility motivation in infertile women.
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Objective:To investigate the effects of low anterior resection syndrome (LARS) on psychological and physical function and quality of life in patients with rectal cancer.Methods:From May 2014 to May 2019, 200 patients were included. LARS scale score was adopted, and the clinical and pathological data were collected. Univariate analysis and multivariate Logistic regression analysis were performed. the European Organization for Research and Treatment of Cancer Quality of Life core questionnaire and psychological distress management screening tool survey were conducted to evaluate the quality of life and psychological state. The incidence of postoperative sexual dysfunction in male patients was analyzed.Results:The incidence of LARS was 43.0%. Multivariate analysis showed that body mass index ≥24 kg/m 2, anastomotic leakage, anastomotic distance ≤5 cm from anal margin, and preoperative radiotherapy were independent risk factors for LARS ( OR=2.123, 15.109, 7.302, 12.682, all P<0.05).The overall health level and the scores of physical function and emotional function in the functional dimension of patients in the severe LARS group were significantly lower than those in the no/mild LARS group ( t=5.788, 8.831, 8.745, all P<0.05). The scores of fatigue and diarrhea were significantly higher than those in the no/mild LARS group ( t=26.280, 49.476, all P<0.05). The psychological distress thermometer score and the scores of communication , emotional and physical problems in the severe LARS group were significantly higher than those in the no/mild LARS group ( t=4.246, 6.563, 5.913, 4.408, all P<0.05). Conclusion:LARS is a common complication after Dixon procedure for rectal cancer. Body mass index ≥24 kg/m 2, anastomotic leakage, anastomotic distance from anal margin ≤5 cm, and preoperative radiotherapy are independent risk factors for LARS.
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In 2011,the International Association for the Study of Lung Cancer(IASLC),American Thoracic Society(ATS)and European Respiratory Society(ERS)simultaneously defined micropapillary pattern(MPP)-based lung adenocarcinoma as an independent pathological type:micropapillary-predominant adenocarcinoma(MPA).Its histological and clinical specificities have attracted broad attention from researchers.Lung adenocarcinoma with a micropapillary pattern(MPPAC)often shows biological behaviors indicative of poor prognosis,including strong invasion,high metastasis rate and easy recurrence after surgical treatment.At present,the clinical diagnosis of MPPAC depends on postoperative pathological examination,but systematic studies on its pathological heterogeneity,molecular biological characteristics,clinical features and prognosis remains scarce.This review aims to focus on the research progress of the pathological and clinical features of MPPAC.
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OBJECTIVE To explore the intervention effect and related mechanism of Tongxinluo capsule on renal fibrosis in rats with diabetic nephropathy (DN). METHODS Eight rats were selected as control group (ordinary feed), the remaining rats were given high-glucose and high-fat diet combined with ip injection of streptozotocin (35 mg/kg) to induce DN model. Model rats were randomly divided into model group (purified water), irbesartan group (positive control, 14.12 mg/kg) and Tongxinluo capsule group (0.3 g/kg), including 12 rats in the model group and 11 rats for each of the other two groups. All groups were given relevant medicine or water intragastrically, once a day, for 16 consecutive weeks. After the last medication, fasting blood glucose and 24 h urinary total protein (24 h UTP) were detected. Pathological changes in renal cortex of rats in each group were observed. Serum levels of tissue-type plasminogen activator (PA) and plasminogen activator inhibitor 1 (PAI-1) were measured. mRNA expressions of transforming growth factor-β(1 TGF-β1), type Ⅳ collagen(COL-Ⅳ), Wnt4 and β-catenin in renal cortex of rats were detected. The protein depositions or expressions of TGF-β1, COL-Ⅳ, focal adhesion kinase (FAK), integrin-linked kinase (ILK), E-cadherin, PA, PAI-1, Wnt4 and β-catenin in renal cortex of rats were observed or determined. RESULTS Compared with model group, 24 h UTP of rats in Tongxinluo capsule group were all significantly reduced (P<0.05); pathological damage and fibrosis of renal cortex were relieved; the expression of PA in serum and renal cortex was significantly increased, while PAI-1 level was significantly reduced (P<0.05); the depositions of COL-Ⅳ and TGF-β1 in renal cortex were all reduced, and corresponding mRNA expression was decreased significantly (P<0.05); the depositions of ILK and FAK were decreased, while the deposition of E-cadherin was increased; protein and mRNA expressions of Wnt4 and β-catenin were significantly reduced (P<0.05). CONCLUSIONS Tongxinluo capsule can relieve pathological damage to renal tissue and renal fibrosis of DN model rats, and reduce extracellular matrix deposition. The mechanism may be related to regulation of fibrinolytic system activity, the decrease of ILK and FAK expression, and inhibition of Wnt/β-catenin signaling pathway.
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Rosae Radix et Rhizoma is a herbal medicine in a variety of famous Chinese patent medicines, while the quality standard for this medicine remains to be developed due to the insufficient research on the quality of Rosae Radix et Rhizoma from different sources. Therefore, this study comprehensively analyzed the components in Rosae Radix et Rhizoma of different sources from the aspects of extract, component category content, identification based on thin-lay chromatography, active component content determination, and fingerprint, so as to improve the quality control. The results showed that the content of chemical components varied in the samples of different sources, while there was little difference in the chemical composition among the samples. The content of components in the roots of Rosa laevigata was higher than that in the other two species, and the content of components in the roots was higher than that in the stems. The fingerprints of triterpenoids and non-triterpenoids were established, and the content of five main triterpenoids including multiflorin, rosamultin, myrianthic acid, rosolic acid, and tormentic acid in Rosae Radix et Rhizoma was determined. The results were consistent with those of major component categories. In conclusion, the quality of Rosae Radix et Rhizoma is associated with the plant species, producing area, and medicinal parts. The method established in this study lays a foundation for improving the quality standard of Rosae Radix et Rhizoma and provides data support for the rational use of the stem.
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Medicamentos Herbarios Chinos/química , Rizoma/química , Raíces de Plantas/química , Plantas Medicinales , Control de CalidadRESUMEN
Objective: We analyze the characteristics of Clostridioides difficile (C. difficile) infection among diarrhea patients in Kunming from 2018 to 2020 and provide evidence for follow-up surveillance and prevention. Methods: A total of 388 fecal samples of diarrhea patients from four sentinel hospitals in Yunnan Province from 2018 to 2020 were collected. Real-time quantitative PCR was used to detect the fecal toxin genes of C. difficile. The positive fecal samples isolated the bacteria, and isolates were identified by mass spectrometry. The genomic DNA of the strains was extracted for multi-locus sequence typing (MLST). The fecal toxin, strain isolation, and clinical patient characteristics, including co-infection with other pathogens, were analyzed. Results: Among the 388 fecal samples, 47 samples with positive reference genes of C. difficile were positive, with a total positive rate of 12.11%. There were 4 (8.51%) non-toxigenic and 43 (91.49%) toxigenic ones. A total of 18 strains C. difficile were isolated from 47 positive specimens, and the isolation rate of positive specimens was 38.30%. Among them, 14 strains were positive for tcdA, tcdB, tcdC, tcdR, and tcdE. All 18 strains of C. difficile were negative for binary toxins. The MLST results showed 10 sequence types (ST), including 5 strains of ST37, accounting for 27.78%; 2 strains of ST129, ST3, ST54, and ST2, respectively; and 1 strain of ST35, ST532, ST48, ST27, and ST39, respectively. Fecal toxin gene positive (tcdB+) results were statistically associated with the patient's age group and with or without fever before the visit; positive isolates were only statistically associated with the patient's age group. In addition, some C. difficile patients have co-infection with other diarrhea-related viruses. Conclusions: The infection of C. difficile in diarrhea patients in Kunming is mostly toxigenic strains, and the high diversity of strains was identified using the MLST method. Therefore, the surveillance and prevention of C. difficile should be strengthened.
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Humanos , Toxinas Bacterianas/genética , Enterotoxinas/genética , Clostridioides difficile/genética , Tipificación de Secuencias Multilocus , Coinfección , Proteínas Bacterianas/genética , China/epidemiología , Infecciones por Clostridium/epidemiología , Diarrea/microbiologíaRESUMEN
Objective: To establish and optimize PCR methods for the gene encoding of Clostridium perfringens β2 toxin (cpb2) and atypical-cpb2 (aty-cpb2), analyze the epidemiological characteristics and genetic polymorphism of the cpb2 of Clostridium perfringens in 9 Chinese areas from 2016 to 2021. Methods: The cpb2 of 188 Clostridium perfringens strains were examined by PCR; the cpb2 sequences were acquired by whole-genome sequencing to analyze the genetic polymorphism. Using Mega 11 and the Makeblastdb tool, a phylogenetic tree, and cpb2-library based on 110 strains carrying the cpb2 were produced. Using the Blastn technique, a comparison was made to discover sequence similarity between consensus-cpb2 (con-cpb2) and aty-cpb2. Results: The specificity of PCR assay for the cpb2 and aty-cpb2 was verified. The PCR results for cpb2 amplification were highly consistent with the whole-genome sequencing approach (Kappa=0.946, P<0.001). A total of 107 strains from nine regions in China carried cpb2, 94 types A strains carried aty-cpb2, 6 types A strains carried con-cpb2, and 7 types F strains carried aty-cpb2. The nucleotide sequence similarity between the two coding genes was 68.97%-70.97%, and the similarity between the same coding genes was 98.00%-100.00%. Conclusions: In this study, a specific PCR method for cpb2 toxin was developed, and the previous PCR method for detecting aty-cpb2 was improved. aty-cpb2 is the primary gene encoding of β2 toxin. There is a significant nucleotide sequence variance between the various cpb2 genotypes.
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Humanos , Clostridium perfringens/genética , Infecciones por Clostridium , Toxinas Bacterianas/genética , Filogenia , Reacción en Cadena de la Polimerasa , Polimorfismo GenéticoRESUMEN
Objective: To analyze the efficacy and safety of letermovir in primary prophylaxis of cytomegalovirus (CMV) reactivation in patients receiving haploidentical hematopoietic stem cell transplantation. Methods: This retrospective, cohort study was conducted using data of patients who underwent haploidentical transplantation at Peking University Institute of Hematology and received letermovir for primary prophylaxis between May 1, 2022 and August 30, 2022. The inclusion criteria of the letermovir group were as follows: letermovir initiation within 30 days after transplantation and continuation for≥90 days after transplantation. Patients who underwent haploidentical transplantation within the same time period but did not receive letermovir prophylaxis were selected in a 1∶4 ratio as controls. The main outcomes were the incidence of CMV infection and CMV disease after transplantation as well as the possible effects of letermovir on acute graft versus host disease (aGVHD), non-relapse mortality (NRM), and bone marrow suppression. Categorical variables were analyzed by chi-square test, and continuous variables were analyzed by Mann-Whitney U test. The Kaplan-Meier method was used for evaluating incidence differences. Results: Seventeen patients were included in the letermovir prophylaxis group. The median patient age in the letermovir group was significantly greater than that in the control group (43 yr vs. 15 yr; Z=-4.28, P<0.001). The two groups showed no significant difference in sex distribution and primary diseases, etc. (all P>0.05). The proportion of CMV-seronegative donors was significantly higher in the letermovir prophylaxis group in comparison with the control group (8/17 vs. 0/68, χ2=35.32, P<0.001). Three out of the 17 patients in the letermovir group experienced CMV reactivation, which was significantly lower than the incidence of CMV reactivation in the control group (3/17 vs. 40/68, χ2=9.23, P=0.002), and no CMV disease development observed in the letermovir group. Letermovir showed no significant effects on platelet engraftment (P=0.105), aGVHD (P=0.348), and 100-day NRM (P=0.474). Conclusions: Preliminary data suggest that letermovir may effectively reduce the incidence of CMV infection after haploidentical transplantation without influencing aGVHD, NRM, and bone marrow suppression. Prospective randomized controlled studies are required to further verify these findings.
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Humanos , Citomegalovirus , Estudios Retrospectivos , Estudios de Cohortes , Estudios Prospectivos , Infecciones por Citomegalovirus/prevención & control , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Enfermedad Injerto contra Huésped/prevención & control , Recurrencia , Antivirales/uso terapéuticoRESUMEN
Headache is a common clinical complication of ischemic stroke. As a precursor of stroke, headache occurs repeatedly in the convalescent period of ischemic stroke, leading to secondary stroke and seriously hindering patients' rehabilitation. Currently, it is believed that the pathogenesis of ischemic stroke-related headache is associated with the abnormal release of vasoactive substances, high platelet aggregation, and stimulation of intracranial pain-sensitive structures. The active ingredients in traditional Chinese medicines(TCM) with the effects of activating blood to resolve stasis and clearing heat to release exterior can protect brain tissue and relieve headache by reducing the release of inflammatory cytokines, alleviating antioxidant stress, inhibiting neuronal apoptosis and so on. This paper introduces the research progress in the potential mechanism and TCM treatment of ischemic stroke-related headache, aiming to provide reference for further research and drug development of this complication.