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OBJECTIVE To investigate the effect and mechanism of Astragalus polysaccharide （APS） on peritoneal fibrosis and angiogenesis in rats with peritoneal dialysis （PD）. METHODS Rats were randomly divided into normal control group （Control group）， model group （PD group）， 70 mg/kg APS group （APS-L group）， 140 mg/kg APS group （APS-H group）， and 140 mg/kg APS+40 mg/kg hypoxia-inducible factor-1α （HIF-1α） agonist DMOG group （APS-H+DMOG group）， with 12 rats in each group. PD rat models were constructed in the last four groups of rats. Administration groups were given APS intragastrically and DMOG intraperitoneally. Control group and PD group were given constant volume of normal saline intragastrically， once a day， for 4 consecutive weeks. After the last medication， the peritoneal ultrafiltration （UF）， mass transfer of glucose （MTG）， the levels of serum creatinine （Scr） and blood urea nitrogen （BUN） were detected in rats； peritoneal histomorphology and peritoneal fibrosis （peritoneal thickness and proportion of collagen fiber deposition） were observed； the microvascular density and the expression levels of α-smooth muscle actin （α-SMA）， laminin （LN）， HIF-1α and vascular endothelial growth factor （VEGF） proteins were detected in peritoneal tissue of rats. RESULTS Compared with Control group， the mesothelium of rats in the PD group was loosely arranged and shed， inflammatory cells infiltrated， the peritoneal thickness and proportion of collagen fiber deposition were increased significantly （P＜0.05）. The levels of MTG， Scr and BUN in serum， microvascular density and the expressions of α-SMA， LN， HIF-1α and VEGF proteins were significantly increased， while the level of UF was significantly decreased （P＜ 0.05）； compared with PD group， the levels of above indexes were significantly reversed in APS-L and APS-H groups （P＜0.05）， and the improvement of APS-H group was better than APS-L group （P＜0.05）. Compared with APS-H group， the levels of above indexes in APS-H+DMOG group were all reversed （P＜0.05）. CONCLUSIONS APS inhibits peritoneal fibrosis and angioge-nesis in PD rats by inhibiting HIF-1α/VEGF signaling pathway.
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ObjectiveTo induce the rat model of ulcerative colitis （UC） with spleen-kidney Yang deficiency and liver depression， and explore the efficacy and mechanism of Sishenwan combined with Tongxie Yaofang （SSW&TXYF） based on the therapeutic principles of tonifying spleen， soothing liver， warming kidney， and astringing intestine. MethodSixty male SD rats were randomized into normal， model， mesalazine， and high-， medium-， and low-dose SSW&TXYF groups. The rats in other groups except the normal group were administrated with Sennae Folium decoction and hydrocortisone and received tail clamping for 14 days. On day 14， rats received enema with TNBS-ethanol solution to induce UC. The rats were administrated with corresponding drugs from day 15 of modeling， and the body weight and mental state were observed and recorded. The sucrose preference test was performed from day 25. On day 28， the rectal temperature was measured， and the rats were administrated with 3% D-xylose solution at a dose of 10 mL·kg-1 by gavage. Blood was sampled 1 h later， from which the serum was collected for measurement of the D-xylose content. The serum， hippocampus， and colorectum samples of rats were collected on day 29. The levels of gastrin （GAS）， adrenocorticotropic hormone （ACTH）， corticosterone （CORT）， cyclic adenosine monophosphate （cAMP）， cyclic guanosine monophosphate （cGMP）， interleukin （IL）-4， tumor necrosis factor （TNF）-α， and interferon （IFN）-γ in the serum and 5-hydroxytryptamine （5-HT） in the hippocampus were determined by enzyme-linked immunosorbent assay. Hematoxylin-eosin staining was employed to reveal the colonic lesions. The mRNA and protein levels of p38 mitogen-activated protein kinase （MAPK）， extracellular signal-regulated kinase （ERK）， and c-Jun N-terminal kinase （JNK） in the colon tissue were determined by Real-time PCR and Western blot， respectively. ResultCompared with the normal group， the model group showed decreased body weight， anal temperature， and D-xylose content in the serum and increased GAS content （P<0.01）. The modeling led to cAMP/cGMP unbalance and decreased the ACTH and CORT content in the serum （P<0.01）， the preference for sucrose water， and the 5-HT content in the hippocampus （P<0.01）. Moreover， it shortened the colorectal length and caused massive infiltration of inflammatory cells and severe structural damage in the colon tissue. High， medium， and low doses of SSW&TXYF improved above indicators （P<0.05， P<0.01）， reduced inflammatory infiltration， and repaired the pathological damage of the tissue. Compared with the normal group， the model group showed lowered IL-4 level （P<0.01） and elevated TNF-α and IFN-γ levels （P<0.05， P<0.01） in the serum， as well as up-regulated expression of p38 MAPK， ERK， and JNK （P<0.05， P<0.01）. Compared with the model group， SSW&TXYF elevated the IL-4 level （P<0.01）， lowered the TNF-α and IFN-γ levels （P<0.05， P<0.01）， and down-regulated the mRNA and protein levels of p38 MAPK， ERK， and JNK （P<0.05， P<0.01）. ConclusionA rat model of UC with spleen-kidney Yang deficiency and liver depression was successfully established. SSW&TXYF can significantly mitigate this syndrome by reducing the inflammatory response in the colon and inhibiting the MAPK pathway.
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Sesquiterpenoids are widely found in nature, while nitrobenzoyl sesquiterpenoids are relatively rare. Twelve natural nitrobenzoyl sesquiterpenoids were all derived from marine Aspergillus fungi, which are typical natural products with marine characteristics. These natural products exhibit good antitumor, antiviral, and inhibition of osteoclast differentiation activity, especially in the treatment of osteoclast-related diseases, showing good medicinal development value. This article reviews the natural product sources, chemical structure, chemical synthesis, biosynthesis, bioactivity, and pharmacological mechanisms of nitrobenzoyl sesquiterpenoids and predicts and discusses their absorption, distribution, metabolism, excretion, toxicity (ADME/T), and drug-likeness, providing a comprehensive understanding of the natural products of nitrobenzoyl sesquiterpenoids from marine sources and their potential for pharmaceutical development.
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OBJECTIVES@#To investigate the distribution characteristics of non-bacterial pathogens in community-acquired pneumonia (CAP) in children.@*METHODS@#A total of 1 788 CAP children admitted to Shenyang Children's Hospital from December 2021 to November 2022 were selected. Multiple RT-PCR and capillary electrophoresis were used to detect 10 viral pathogens and 2 atypical pathogens, and serum antibodies of Chlamydial pneumoniae (Ch) and Mycoplasma pneumoniae (MP) were detected. The distribution characteristics of different pathogens were analyzed.@*RESULTS@#Among the 1 788 CAP children, 1 295 children were pathogen-positive, with a positive rate of 72.43% (1 295/1 788), including a viral pathogen positive rate of 59.68% (1 067/1 788) and an atypical pathogen positive rate of 22.04% (394/1 788). The positive rates from high to low were MP, respiratory syncytial virus (RSV), influenza B virus (IVB), human metapneumovirus (HMPV), human rhinovirus (HRV), human parainfluenza virus (HPIV), influenza A virus (IVA), bocavirus (BoV), human adenovirus (HADV), Ch, and human coronavirus (HCOV). RSV and MP were the main pathogens in spring; MP had the highest positive rate in summer, followed by IVA; HMPV had the highest positive rate in autumn; IVB and RSV were the main pathogens in winter. The positive rate of MP in girls was higher than that in boys (P<0.05), and there were no significant differences in other pathogens between genders (P>0.05). The positivity rates of certain pathogens differed among age groups (P<0.05): the positivity rate of MP was highest in the >6 year-old group; the positivity rates of RSV and Ch were highest in the <1 year-old group; the positivity rates of HPIV and IVB were highest in the 1 to <3 year-old group. RSV, MP, HRV, and HMPV were the main pathogens in children with severe pneumonia, while MP was the primary pathogen in children with lobar pneumonia, and MP, IVB, HMPV, RSV, and HRV were the top 5 pathogens in acute bronchopneumonia.@*CONCLUSIONS@#MP, RSV, IVB, HMPV, and HRV are the main pathogens of CAP in children, and there are certain differences in the positive rates of respiratory pathogens among children of different ages, genders, and seasons.
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Humans , Child , Female , Male , Infant , Child, Preschool , Pneumonia , Respiratory Syncytial Virus, Human , Antibodies , Community-Acquired Infections , Hospitalization , Influenza B virus , Mycoplasma pneumoniaeالملخص
Objective: To systematically evaluate the correlation between prenatal steroid exposure and hypoglycemia in late preterm neonates. Methods: Eight databases in either Chinese or English, including PubMed, the Cochrane Library, Embase, Medline, Scopus, CNKI, Wanfang and VIP, were searched to extract the studies on the correlation between prenatal steroid exposure and hypoglycemia in late preterm neonates published from the establishment of each database to December 2022. The Meta-analysis was performed using Stata 14.0 statistical software. Results: A total of 9 studies were included in this Meta-analysis, including 6 retrospective cohort studies, 2 prospective cohort studies and 1 randomized controlled trial (RCT) study, involving 9 143 premature infants. The Meta-analysis showed that prenatal steroid exposure increased the risk of late preterm neonatal hypoglycemia (RR=1.55, 95%CI 1.25-1.91, P<0.001). The similar correlation between prenatal steroid exposure and hypoglycemia in late preterm neonates was all found in the following subgroups: North America (RR=1.57, 95%CI 1.37-1.80, P<0.001), enrolling pregnant women with gestational diabetes (RR=1.62, 95%CI 1.26-2.08, P<0.001), A-grade literature quality (RR=1.43, 95%CI 1.14-1.79, P=0.002), criteria for hypoglycemia ≤40 mg/dl (1 mg/dl=0.056 mmol/L, RR=1.49, 95%CI 1.28-1.73, P<0.001), sample size of 501-1 500 (RR=1.69, 95%CI 1.19-2.40, P=0.003) and >1 500 (RR=1.65, 95%CI 1.48-1.83, P<0.001), steroid injection dosage and frequency of 12 mg 2 times (RR=1.66, 95%CI 1.50-1.84, P<0.001), the time interval from antenatal corticosteroid administration to delivery of 24-47 h (RR=1.98, 95%CI 1.26-3.10, P=0.003), unadjusted gestational age (RR=1.78, 95%CI 1.02-3.10,P=0.043) and unadjusted birth weight (RR=1.80, 95%CI 1.22-2.66, P=0.003). Meta-regression results showed that steroid injection frequency and dose were the main sources of high heterogeneity among studies (P=0.030). Conclusion: Prenatal steroid exposure may be a risk factor for hypoglycemia in late preterm neonates.
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Female , Humans , Infant , Infant, Newborn , Pregnancy , Birth Weight , Hypoglycemia/chemically induced , Infant, Premature , Randomized Controlled Trials as Topic , Steroids/adverse effects , Prenatal Exposure Delayed Effectsالملخص
Objective: To characterize the incidence density of systematic lupus erythematosus (SLE) in Yinzhou District of Ningbo from 2016 to 2021, and compare the age and gender specific differences. Methods: A retrospective cohort study was conducted based on the related data from 2015 to 2021 collected from the Health Information Platform of Yinzhou. Suspected SLE cases in local residents were identified by fuzzy matching of International Classification of Diseases 10th edition code "M32" or Chinese text "lupus". The classification criteria from Systemic Lupus International Collaboration Clinics-2012 and The European League Against Rheumatism/American College of Rheumatology-2019 were used for case verification. SLE cases were identified with specific algorithm based on verification results, and new cases were identified with 1 year as the washout period. The incidence density and 95%CI were estimated by Poisson distribution. Results: From 2016 to 2021, a total of 1 551 921 permanent residents were registered in Yinzhou, in whom 51.52% were women. The M(Q1,Q3) age at enrollment was 40.38 (27.54, 53.54) years. The M(Q1,Q3) of follow-up person-years was 3.83 (0.41, 5.83) years. There were 451 new SLE cases, in which 352 were women (78.05%). The 6-year incidence density was 8.14/100 000 person-years (95%CI: 7.41/100 000 person-years-8.93/100 000 person-years) for the total population, 3.68/100 000 person-years (95%CI: 2.99/100 000 person-years-4.48/100 000 person-years) for men and 12.37/100 000 person-years (95%CI: 11.11/100 000 person-years- 13.73/100 000 person-years) for women. The incidence density in men appeared a small peak at 20-29 years old, and began to increase with age from 40 years old. The incidence density in women was highest in age group 20-29 years (16.57/100 000 person-years) and remained to be high until 30-79 years old. The incidence density of SLE in Yinzhou show no significant temporal trend from 2016 to 2021 (men: P=0.848; women: P=1.000). Conclusions: The incidence density of SLE in Yinzhou from 2016 to 2021 was similar to those of other areas in China. SLE has a high incidence in women, especially in the young and elderly, suggesting that more attention should be paid to the diagnosis and treatment of SLE in women.
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Adult , Aged , Female , Humans , Male , Middle Aged , Young Adult , Asian People , Incidence , Lupus Erythematosus, Systemic/diagnosis , Retrospective Studies , China/epidemiologyالملخص
The efficacy of HPV vaccine in preventing cervical cancer has been demonstrated in numerous clinical trials and clinical uses. The follow-up after clinical trials usually last for 5-6 years to evaluate the long-term efficacy, and a series of long-term follow-up studies have been conducted in some regions. The literature retrieval of HPV vaccine long term efficiency research both at home and abroad indicated that the protective efficacy of the vaccine against vaccine-type-related cervical intraepithelial neoplasia grade 2 and above is higher than 90%.
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Humans , Papillomaviridae , Biomedical Research , Papillomavirus Vaccinesالملخص
Objective: To investigate the outcome of patients with esophagogastric junction cancer undergoing thoracoscopic laparoscopy-assisted Ivor-Lewis resection. Methods: Eighty-four patients who were diagnosed with esophagogastric junction cancer and underwent Ivor-Lewis resection assisted by thoracoscopic laparoscopy at the National Cancer Center from October 2019 to April 2022 were collected. The neoadjuvant treatment mode, surgical safety and clinicopathological characteristics were analyzed. Results: Siewert type Ⅱ (92.8%) and adenocarcinoma (95.2%) were predominant in the cases. A total of 2 774 lymph nodes were dissected in 84 patients. The average number was 33 per case, and the median was 31. Lymph node metastasis was found in 45 patients, and the lymph node metastasis rate was 53.6% (45/84). The total number of lymph node metastasis was 294, and the degree of lymph node metastasis was 10.6%(294/2 774). Among them, abdominal lymph nodes (100%, 45/45) were more likely to metastasize than thoracic lymph nodes (13.3%, 6/45). Sixty-eight patients received neoadjuvant therapy before surgery, and nine patients achieved pathological complete remission (pCR) (13.2%, 9/68). Eighty-three patients had negative surgical margins and underwent R0 resection (98.8%, 83/84). One patient, the intraoperative frozen pathology suggested resection margin was negative, while vascular tumor thrombus was seen on the postoperative pathological margin, R1 resection was performed (1.2%, 1/84). The average operation time of the 84 patients was 234.5 (199.3, 275.0) minutes, and the intraoperative blood loss was 90 (80, 100) ml. One case of intraoperative blood transfusion, one case of postoperative transfer to ICU ward, two cases of postoperative anastomotic leakage, one case of pleural effusion requiring catheter drainage, one case of small intestinal hernia with 12mm poke hole, no postoperative intestinal obstruction, chyle leakage and other complications were observed. The number of deaths within 30 days after surgery was 0. Number of lymph nodes dissection, operation duration, and intraoperative blood loss were not related to whether neoadjuvant therapy was performed (P>0.05). Preoperative neoadjuvant chemotherapy combined with radiotherapy or immunotherapy was not related to whether postoperative pathology achieved pCR (P>0.05). Conclusion: Laparoscopic-assisted Ivor-Lewis surgery for esophagogastric junction cancer has a low incidence of intraoperative and postoperative complications, high safety, wide range of lymph node dissection, and sufficient margin length, which is worthy of clinical promotion.
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Humans , Blood Loss, Surgical , Lymphatic Metastasis/pathology , Esophagectomy , Esophageal Neoplasms/pathology , Retrospective Studies , Lymph Node Excision , Postoperative Complications/epidemiology , Laparoscopy , Esophagogastric Junction/pathologyالملخص
Objective: To analyze the clinical characteristics and prognosis of adenovirus infection after allogeneic hematopoietic stem cell transplantation. Methods: A total of 26 patients with adenovirus infection admitted to the posttransplant ward of the First Affiliated Hospital of Soochow University from 2018 to 2022 were enrolled. Their data on baseline and clinical characteristics, treatment, and follow-up were analyzed. Results: The median patient age was 30 (22, 44) years. Twenty-two patients received related haploid stem cell transplantation, three received unrelated stem cell transplantation, and one received umbilical cord stem cell transplantation. Antithymocyte globulin was included in the conditioning regimen in 25 patients. The median time of adenovirus infection was +95 (+44, +152) days. The median peripheral blood lymphocyte count was 0.30 (0.11, 0.69) × 10(9)/L. Twelve patients had acute graft-versus-host disease. Twenty-four patients received antirejection therapies at diagnosis. Sixteen cases had combined infection with other pathogens with adenovirus infection. Eight cases were diagnosed as asymptomatic infection, and 18 were diagnosed as adenovirus disease, including pneumonia (38.89% ) , gastrointestinal disease (38.89% ) , encephalitis (33.33% ) , hepatitis (5.56% ) , and urinary tract inflammation (5.56% ) . The age of >30 years was a risk factor for adenovirus disease (P=0.03) . Eighteen patients received tapering of immunosuppression, and all 26 patients received at least one antiviral drug. Other treatments included high-dose gamma globulin and donor lymphocyte infusion. Adenovirus infection improved in 10 cases and progressed in 16 cases. The median follow-up time was 30 (7, 237) days. Twenty-two patients died. The all-cause mortality rate was (88.5±7.1) % , and the attributable mortality rate was 45.5% . There was no significant difference in the 100 d survival rate between asymptomatic infected patients and patients diagnosed with adenovirus disease (37.5% vs 22.2% , HR=1.83, 95% CI 0.66-5.04, P=0.24) . Conclusion: The age of >30 years was a risk factor for adenovirus disease. Mortality was high in patients with adenovirus infection after allogeneic hematopoietic stem cell transplantation.
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Humans , Adult , Hematopoietic Stem Cell Transplantation/adverse effects , Graft vs Host Disease/etiology , Antilymphocyte Serum/therapeutic use , Transplantation, Homologous/adverse effects , Adenoviridae Infections/therapy , Transplantation Conditioning/adverse effects , Retrospective Studiesالملخص
Pinellia ternata is an important medicinal plant, and its growth and development are easily threatened by high temperature. In this study, comprehensive research on physiological, cytological and transcriptional responses to different levels of heat stress were conducted on a typical phenotype of P. ternata. First, P. ternata exhibited tolerance to the increased temperature, which was supported by normal growing leaves, as well as decreased and sustained photosynthetic parameters. Severe stress aggravated the damages, and P. ternata displayed an obvious leaf senescence phenotype, with significantly increased SOD and POD activities (46% and 213%). In addition, mesophyll cells were seriously damaged, chloroplast thylakoid was fuzzy, grana lamellae and stroma lamellae were obviously broken, and grana thylakoids were stacked, resulting in a dramatically declined photosynthetic rate (74.6%). Moreover, a total of 16 808 genes were significantly differential expressed during this process, most of which were involved in photosynthesis, transmembrane transporter activity and plastid metabolism. The number of differentially expressed transcription factors in MYB and bHLH families was the largest, indicating that these genes might participate in heat stress response in P. ternata. These findings provide insight into the response to high temperature and facilitate the standardized cultivation of P. ternata.
الموضوعات
Pinellia/genetics , Heat-Shock Response/genetics , Photosynthesis/genetics , Plants, Medicinal/genetics , Phenotypeالملخص
AIM:To investigate the effect of 3% diquafosol sodium eye drops combined with intense pulsed light on the treatment of meibomian gland dysfunction and the change of meibomian glands.METHODS: Prospective study. A total of 141 patients(282 eyes)who were diagnosed with meibomian gland dysfunction from January 2021 to May 2022 in our hospital were selected and they were randomly divided into the control group(73 cases, 146 eyes)and the observation group(68 cases, 136 eyes)according to random number table. The control group was given 0.3% sodium hyaluronate eye drops combined with intense pulsed light, and the observation group was treated with 3% diquafosol sodium eye drops combined with intense pulsed light. The subjective symptom score, physical sign score, non-invasive tear break-up time, tear meniscus height, lipid layer thickness, and meibomian gland density before and after the treatment were compared between the two groups at 2wk after the end of treatment.RESULTS: There were no differences in the subjective symptom score, physical sign score, non-invasive tear break-up time, tear meniscus height, lipid layer thickness, and meibomian gland density between the two groups of patients before treatment(P>0.05). After 2wk of treatment, the symptom scores and physical sign scores of patients in the two groups continued to decrease, non-invasive tear break-up time and lipid layer thickness continued to increase, and the meibomian gland density also increased. The tear meniscus height in the observation group increased, while the control group showed no significant changes. The observation group had better clinical indicators than the control group(P<0.05). No obvious complications were observed in all patients.CONCLUSION: The combination of diquafosol sodium eye drops and intense pulsed light is synergistic in the treatment of meibomian gland dysfunction, with significant therapeutic effects and improvement of meibomian gland repair, which is significantly superior to simple intense pulsed light therapy.
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As a member of G protein coupled-receptors superfamily, free fatty acid receptor 1 (FFAR1), is also known as GPR40, has been shown to regulate numerous pathophysiological processes in a variety of tissues and organs. The activated FFAR1 has a variety of biological functions. For instance, it can not only regulate metabolism of fatty acids and glucose, but also play an important role in immune inflammatory response, it may be a potential drug target for the treatment of various chronic inflammatory diseases. In this review, we focus on the recent researches of FFAR1's action in the regulation of pathophysiological processes, its molecular mechanism and new agonists development. At the same time, this review will take the discovery of series FFAR1 agonists as examples, and display the applied prospects of FFAR1.
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At present， major depressive disorder （MDD） is highly prevalent with advanced neurological disorders as the main pathological manifestations. As the physiological function bearer of higher neural activity， gray matter has become the focus of MDD treatment. However， recent research has shown that white matter and gray matter are independent of each other in the central nervous system （CNS）， and their functions are integrated and linked. In addition to gray matter damage， white matter damage is also the core driving event of disease progression and determines the outcome of MDD. At the treatment level， the current drug treatment of MDD mainly focuses on gray matter repair， while ignoring the importance of white matter integrity for the treatment of the disease， which has become the weakness of the current treatment of MDD. Traditional Chinese medicine （TCM） has good application potential in white matter repair. This paper elaborated on the following three aspects. ① The roles of white matter damage in the occurrence and development of MDD were summarized. ② The key link of white matter repair in MDD was elaborated with microglia microenvironment regulation as the entry point. ③ The application value of TCM in white matter repair in MDD was analyzed. This review aims to highlight the importance of white matter integrity in the treatment of MDD and is expected to expand the understanding dimension of the activity of related Chinese medicines in MDD from the perspective of white matter repair and analyze its potential application value.
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There are many multi-original medicinal materials in Chinese Pharmacopoeia, and the mixed use of medicinal materials from different sources is common, which has certain influence on the stability of clinical medication. In this study, pyrosequencing technology was used to screen species-specific single nucleotide polymorphisms (SNP) from commonly used DNA barcode sequences, and a rapid and accurate molecular identification method for original species in mixed medicinal powder of Epimedii Folium was established. Multiple sequence alignment analysis showed that the 176th (C/T) mutation and the 196th (A/G) mutation of ITS, the 123rd (C/G) mutation of matK and the 892nd (A/C) mutation of rbcL could be used as the unique SNPs of E. sagittatum, E. koreanum, E. brevicornu and E. pubescens, respectively. In this study, the applicability of pyrosequencing and Sanger sequencing methods in the sequencing of mixture samples was investigated from the perspective of sensitivity and stability. Pyrosequencing method has higher detection sensitivity than Sanger sequencing method for low content samples in the mixed samples. Stability analysis showed that pyrosequencing technology could still obtain effective sequencing results for the amplified products of template DNA after 45 min of 95 ℃ high temperature water bath, while the critical point of Sanger sequencing method was 30 min. In this study, a new identification technology of Epimedii Folium mixed powder primordial species based on pyrosequencing and specific SNP was developed, which can quickly and accurately identify the mixed use of Epimedii Folium with high sensitivity and stability, and can also support the identification of different primordial species and mixed powder primordial herbs, which is conducive to ensuring the consistency and stability of clinical medication.
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ObjectiveTo investigate the efficacy of Huangqintang on mouse models of colitis-associated colon cancer （CAC） and explore the mechanism of Huangqintang in regulating immune function and inflammatory response， inhibiting abnormal cell proliferation， and delaying or inhibiting CAC formation in CAC. MethodC57BL/6J mice were randomly divided into a normal group， model group， mesalazine group， and high- and low-dose Huangqintang groups according to body weight， with 12 mice in each group. Except for the normal group， the rest of the mice were given two intraperitoneal injections of 10 mg·kg-1 azomethane （AOM） and allowed to drink 1.5% dextran sodium sulfate （DSS） freely for seven days and water normally for two weeks. Then， two cycles of ''DSS-drinking water'' were repeated. During the administration of DSS， mice in the normal group and model group were given gavage in equal doses of pure water. Mice in the mesalazine group were given 150 mg·kg-1·d-1 mesalamine suspension for gavage， and mice in the high- and low-dose Huangqintang groups were given 18 and 9 g·kg-1·d-1 Huangqintang for gavage， respectively. Each group was given one dose daily until the end of three cycles. After the intervention， the body weight， colon length， and number of colon tumors in each group were measured， and disease activity index （DAI） scores were performed. The serum contents of interleukin-6 （IL-6）， tumor necrosis factor-α （TNF-α）， interleukin-1β （IL-1β）， interleukin-4 （IL-4）， interleukin-10 （IL-10）， and gastrointestinal tumor marker carbohydrate antigen-199 （CA199） were detected by enzyme linked immunosorbent assay （ELISA）. The colonic lesions were observed by hematoxylin-eosin （HE） staining. The expression of proliferative cell-associated antigen （Ki67） was observed by immunohistochemistry. The expression of T lymphocyte subsets （CD3+， CD4+， CD8+， and CD49b+） in mouse plasma was detected by flow cytometry. Fluorescein isothiocyanate-D （FITC-D） content in mouse serum was detected by fluorescent labeling method. The Western blot method was used to detect the expression of Cyclin D1， cyclin-dependent kinase 2 （CDK2）， cyclin-dependent kinase 4 （CDK4）， and tightly junction-related Occludin and Claudin-1. ResultCompared with the normal group， the body weight of mice in the model group decreased. DAI score increased significantly， and the colon became shorter. Pro-inflammatory factors such as IL-6， TNF-α， and IL-1β increased， and IL-6 and TNF-α were significantly increased （P<0.05）. The inflammatory factor IL-4 （P<0.05） and IL-10 were significantly reduced， and the tumor marker CA199 was significantly increased （P<0.01）. HE staining showed that colon lesions， intestinal mucosal epithelial defects with a large number of inflammatory infiltrates， serious crypt structure damage， and glandular arrangement disorder were observed in the model group. Ki67 positive granules were expressed in large areas of colonic tissue. The serum CD4+ and CD4+/CD8+ of mice in the model group decreased significantly （P<0.05）， and CD8+ increased significantly （P<0.05）. The plasma content of FITC-D in the model group was significantly increased （P<0.05）， and the expression of Cyclin D1， CDK2， and CDK4 proteins in colon tissue was significantly increased （P<0.05， P<0.01）. In addition， the expression of Occludin and Claudin-1 was significantly decreased. Compared with the model group， the body weight of mice in the mesalazine group and the high- and low-dose Huangqintang groups increased. DAI score decreased， and the colon became longer. IL-6， TNF-α， and IL-1β expression decreased （P<0.05， P<0.01）， but there was no significant change in IL-4 and IL-10. The content of CA199 was significantly reduced （P<0.05）， and the colomatoid lesions and inflammatory infiltrates were reduced in the mesalazine group and the Huangqintang group. The crypt structure damage was lighter， and the positive expression of Ki67 was reduced. CD4+， CD4+/CD8+， and CD49b+ increased， and the difference was not statistically significant. FITC-D content decreased （P<0.05）. The expression of Cyclin D1， CDK2， and CDK4 decreased （P<0.05， P<0.01）， and Claudin-1 and Occludin protein expression increased in the high-dose Huangqintang group （P<0.05）. ConclusionHuangqintang has a certain delay and inhibitory effect on AOM/DSS-induced inflammatory cancer transformation， and its mechanism of action may be related to regulating immune function and inflammatory response， inhibiting the release of pro-inflammatory factors， repairing damaged intestinal barriers， inhibiting abnormal proliferation of colon cells， and intervening in the formation and development of CAC colon tumors.
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Xenotransplantation holds the promise of being used to address the imbalance between organ supply and demand for clinical transplantation. Pigs have natural features that make them more suitable donors for transplant organs than non-human primates. A series of biological barriers that arise after pig organ transplantation have been overcome by genetic engineering and pharmacological suppression. Mean- while, the gradual maturity of the genetic engineering technology has been significantly optimized for suit- able pigs for xenotransplantation, and promoted the development of pig organ transplantation research. Although it will take time for pig organ xenotransplantation to enter the clinical trial stage, recent studies conducted in a few brain-dead or critically ill patients have exhibited the great potential of porcine xeno- transplantation in solving the imbalance between supply and demand of organs for clinical transplantation.
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Coronavirus disease-19 (COVID-19), a global epidemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), lead to lung injury in millions of people. SARS-CoV-2 can not only cause cytokine storm, acute respiratory distress syndrome and respiratory failure in the phase of acute infection, but also have potential long-term effects on the lungs. Survivors of severe COVID-19 may develop pulmonary fibrosis, resulting in permanent lung injury. In this review we expound the occurrence and development of COVID-19-related pulmonary fibrosis, summarize the key roles of TGF-p/Smad, TGF-fV MAPK, JAK/STAT, Wnt/(3-catenin, YAP/TAZ, NF-KB and PI3K/Akt signal pathways in this process, and analyze the advantages and disadvantages of antiviral drugs, anti-fibrosis drugs, cytokine-targeted drugs, corticosteroids, spironolactone, traditional Chinese medicine prescriptions and lung transplantation in its treatment. This review may provide a reference for the study of pathological mechanism and clinical treatment of COVID-19-re-lated pulmonary fibrosis.
الملخص
OBJECTIVE@#Arsenic (As) and fluoride (F) are two of the most common elements contaminating groundwater resources. A growing number of studies have found that As and F can cause neurotoxicity in infants and children, leading to cognitive, learning, and memory impairments. However, early biomarkers of learning and memory impairment induced by As and/or F remain unclear. In the present study, the mechanisms by which As and/or F cause learning memory impairment are explored at the multi-omics level (microbiome and metabolome).@*METHODS@#We stablished an SD rats model exposed to arsenic and/or fluoride from intrauterine to adult period.@*RESULTS@#Arsenic and/fluoride exposed groups showed reduced neurobehavioral performance and lesions in the hippocampal CA1 region. 16S rRNA gene sequencing revealed that As and/or F exposure significantly altered the composition and diversity of the gut microbiome，featuring the Lachnospiraceae_NK4A136_group, Ruminococcus_1, Prevotellaceae_NK3B31_group, [Eubacterium]_xylanophilum_group. Metabolome analysis showed that As and/or F-induced learning and memory impairment may be related to tryptophan, lipoic acid, glutamate, gamma-aminobutyric acidergic (GABAergic) synapse, and arachidonic acid (AA) metabolism. The gut microbiota, metabolites, and learning memory indicators were significantly correlated.@*CONCLUSION@#Learning memory impairment triggered by As and/or F exposure may be mediated by different gut microbes and their associated metabolites.
الموضوعات
Rats , Animals , Arsenic/toxicity , Fluorides , RNA, Ribosomal, 16S/genetics , Rats, Sprague-Dawley , Metabolome , Microbiotaالملخص
Objective: To analyze the prevalence and the risk factors of fungal sepsis in 25 neonatal intensive care units (NICU) among preterm infants in China, and to provide a basis for preventive strategies of fungal sepsis. Methods: This was a second-analysis of the data from the "reduction of infection in neonatal intensive care units using the evidence-based practice for improving quality" study. The current status of fungal sepsis of the 24 731 preterm infants with the gestational age of <34+0 weeks, who were admitted to 25 participating NICU within 7 days of birth between May 2015 and April 2018 were retrospectively analyzed. These preterm infants were divided into the fungal sepsis group and the without fungal sepsis group according to whether they developed fungal sepsis to analyze the incidences and the microbiology of fungal sepsis. Chi-square test was used to compare the incidences of fungal sepsis in preterm infants with different gestational ages and birth weights and in different NICU. Multivariate Logistic regression analysis was used to study the outcomes of preterm infants with fungal sepsis, which were further compared with those of preterm infants without fungal sepsis. The 144 preterm infants in the fungal sepsis group were matched with 288 preterm infants in the non-fungal sepsis group by propensity score-matched method. Univariate and multivariate Logistic regression analysis were used to analyze the risk factors of fungal sepsis. Results: In all, 166 (0.7%) of the 24 731 preterm infants developed fungal sepsis, with the gestational age of (29.7±2.0) weeks and the birth weight of (1 300±293) g. The incidence of fungal sepsis increased with decreasing gestational age and birth weight (both P<0.001). The preterm infants with gestational age of <32 weeks accounted for 87.3% (145/166). The incidence of fungal sepsis was 1.0% (117/11 438) in very preterm infants and 2.0% (28/1 401) in extremely preterm infants, and was 1.3% (103/8 060) in very low birth weight infants and 1.7% (21/1 211) in extremely low birth weight infants, respectively. There was no fungal sepsis in 3 NICU, and the incidences in the other 22 NICU ranged from 0.7% (10/1 397) to 2.9% (21/724), with significant statistical difference (P<0.001). The pathogens were mainly Candida (150/166, 90.4%), including 59 cases of Candida albicans and 91 cases of non-Candida albicans, of which Candida parapsilosis was the most common (41 cases). Fungal sepsis was independently associated with increased risk of moderate to severe bronchopulmonary dysplasia (BPD) (adjusted OR 1.52, 95%CI 1.04-2.22, P=0.030) and severe retinopathy of prematurity (ROP) (adjusted OR 2.55, 95%CI 1.12-5.80, P=0.025). Previous broad spectrum antibiotics exposure (adjusted OR=2.50, 95%CI 1.50-4.17, P<0.001), prolonged use of central line (adjusted OR=1.05, 95%CI 1.03-1.08, P<0.001) and previous total parenteral nutrition (TPN) duration (adjusted OR=1.04, 95%CI 1.02-1.06, P<0.001) were all independently associated with increasing risk of fungal sepsis. Conclusions: Candida albicans and Candida parapsilosis are the main pathogens of fungal sepsis among preterm infants in Chinese NICU. Preterm infants with fungal sepsis are at increased risk of moderate to severe BPD and severe ROP. Previous broad spectrum antibiotics exposure, prolonged use of central line and prolonged duration of TPN will increase the risk of fungal sepsis. Ongoing initiatives are needed to reduce fungal sepsis based on these risk factors.