Until recently,the common treatment for phenylketonuria (PKU) was a phenylalanine (Phe)-restricted diet.Increasing evidence of suboptimal outcomes was observed in diet-treated individuals.The observation of clinically significant reductions in blood Phe levels in a subset of patients with PKU following oral administration of tetrahydrobiopterin(BH4),a cofactor of phenylalanine hydroxylase.Clinical studies suggest that treatment with BH4 provides better Phe control and increases dietary Phe tolerance,allowing significant relaxation or even discontinuation of dietary Phe restriction.The current knowledge on this novel pharmacologic approach to the treatment of PKU will be discussed.

Total saponins of Panax notoginseng (PNS) have been shown to ameliorate renal interstitial fibrosis. Ginsenoside Rg1, a panaxatriol saponin, is one of the major active molecules from PNS. The present study was undertaken to investigate the effect of ginsenoside Rg1 on renal fibrosis in rats with unilateral ureteral obstruction (UUO). The rats were randomly divided into 3 groups: sham-operation (n=15), UUO (n=15) and UUO with ginsenoside Rg1 treatment (n=15, 50 mg per kg body weight, intraperitoneally (i.p.) injected). The rats were sacrificed on Days 7 and 14 after the surgery. Histological examination demonstrated that ginsenoside Rg1 significantly inhibited interstitial fibrosis including tubular injury as well as collagen deposition. alpha-smooth muscle actin (alpha-SMA) and E-cadherin are two markers of tubular epithelial-myofibroblast transition (TEMT). Interestingly, ginsenoside Rg1 notably decreased alpha-SMA expression and simultaneously enhanced E-cadherin expression. The messenger RNA (mRNA) of transforming growth factor-beta1 (TGF-beta1), a key mediator to regulate TEMT, in the obstructed kidney increased dramatically, but was found to decrease significantly after administration of ginsenoside Rg1. Further study showed that ginsenoside Rg1 considerably decreased the levels of both active TGF-beta1 and phosphorylated Smad2 (pSmad2). Moreover, ginsenoside Rg1 substantially suppressed the expression of thrombospondin-1 (TSP-1), a cytokine which can promote the transcription of TGF-beta1 mRNA and the activation of latent TGF-beta1. These results suggest that ginsenoside Rg1 inhibits renal interstitial fibrosis in rats with UUO. The mechanism might be partly related to the blocking of TEMT via suppressing the expression of TSP-1.
Actins ; biosynthesis ; Animals ; Cadherins ; biosynthesis ; Collagen Type I ; genetics ; metabolism ; Fibronectins ; genetics ; metabolism ; Ginsenosides ; pharmacology ; Immunohistochemistry ; Male ; Nephritis, Interstitial ; drug therapy ; genetics ; metabolism ; pathology ; Panax notoginseng ; chemistry ; RNA, Messenger ; biosynthesis ; genetics ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Reverse Transcriptase Polymerase Chain Reaction ; Smad2 Protein ; biosynthesis ; Thrombospondin 1 ; biosynthesis ; genetics ; Transforming Growth Factor beta1 ; biosynthesis ; genetics ; Ureteral Obstruction ; metabolism ; pathology

OBJECTIVETo evaluate the safety and effectiveness of endourological techniques in the treatment of benign prostate hyperplasia (BPH) in aged high-risk patients.

METHODSWe used endourological techniques in the treatment of 283 BPH patients aged over 70 years and complicated with hydronephrosis, renal failure, heart failure, cerebral infarction, respiratory dysfunction, anemia, diabetes, bladder tumor, or prostate weight over 80 g, TURP (transurethral resection of the prostate) for 112 cases and PKRP (transurethral plasmakinetic resection of the prostate) for the other 171. All the patients were followed up for 1-30 months.

RESULTSIn the TURP group, the scores on IPSS and QOL were decreased from 27.5 +/- 2.8, 5.5 +/- 1.0 to 5.8 +/- 1.2, 1.0 +/- 0.5, and the residual urine volume (RUV) from (75.0 +/- 20.0) ml to (8.0 +/- 3.0) ml, but the maximal flow rate (Qmax) increased from (6.5 +/- 2.0) ml/s to (18.5 +/- 1.5) ml/s (P < 0.05), while in the PKRP group, the scores on IPSS and QOL were decreased from 28.2 +/- 2.2, 5.5 +/- 1.0 to 5.4 +/- 1.6, 1.0 +/- 0.5, and RUV from (80.0 +/- 20.0) ml to (7.0 +/- 3.0) ml, and Qmax increased from (6.8 +/- 2.1) ml/s to (20.0 +/- 1.5) ml/s (P < 0.05). There were no statistically significant differences in IPSS, QOL, Qmax and RUV after treatment between the two groups (P > 0.05), but significantly less complications were found in the PKRP than in the TURP group (P < 0.05).

CONCLUSIONEndourological treatment, especially PKRP, with comprehensive perioperative preparations, unerring operative skills, well-controlled operation time, and intensive postoperative monitoring and nursing, has the advantages of high safety, less bleeding, fewer complications and definite effectiveness for aged high-risk BPH patients.

Aged ; Aged, 80 and over ; Humans ; Male ; Prostatic Hyperplasia ; surgery ; Quality of Life ; Transurethral Resection of Prostate ; methods ; Treatment Outcome

The global patent data on extracorporeal membrane oxygenation(ECMO)in IncomPat Global Patent Database as of August 29,2022 were retrieved.The development trend and layout of ECMO industry were analyzed in terms of global patent application trend,patent distribution,patent technology,major patent applicants and their patent layout.Some suggestions were put forward for the innovation and development of ECMO industry in China so as to provide references for the formulation of national industrial policy,planning of industry technology direction and enterprise technology research and development and patent layout.[Chinese Medical Equipment Journal,2023,44(10):68-75]

BACKGROUND: Acute myeloid leukemia (AML) is a malignant hematological disease, originating from hematopoiesis stem cell differentiation obstruction and clonal proliferation. New reagents or biologicals for the treatment of AML are urgently needed, and exosomes have been identified as candidate biomarkers for disease diagnosis and prognosis. This study aimed to investigate the effects of exosomes from bone marrow mesenchymal stem cells (BMSCs) on AML cells as well as the underlying microRNA (miRNA)-mediated mechanisms. METHODS: Exosomes were isolated using a precipitation method, followed by validation using marker protein expression and nanoparticle tracking analysis. Differentially expressed miRNAs were identified by deep RNA sequencing and confirmed by quantitative real-time polymerase chain reaction (qPCR). Cell proliferation was assessed by the 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium inner salt method, and cell cycle progression and apoptosis were detected by flow cytometry. Functional gene expression was analyzed by qPCR and Western blotting (WB). Significant differences were determined using Student's t test or analysis of variance. RESULTS: BMSCs-derived exosomes effectively suppressed cell proliferation (both P < 0.0001 at 10 and 20 μg/mL) and cell cycle progression (P < 0.01 at G0-G1 stage), and also significantly enhanced cell apoptosis (P < 0.001) in KG-1a cells. There were 1167 differentially expressed miRNAs obtained from BMSCs-derived exosomes compared with KG-1a cell-derived exosomes (P < 0.05). Knockdown of hsa-miR-124-5p in BMSCs abrogated the effects of BMSCs-derived exosomes in regulating KG-1a such as the change in cell proliferation (both P < 0.0001 vs. normal KG-1a cell [NC] at 48 and 72 h). KG-1a cells treated with BMSCs-derived exosomes suppressed expression of structural maintenance of chromosomes 4 (P < 0.001 vs. NC by qPCR and P < 0.0001 vs. NC by WB), which is associated with the progression of various cancers. This BMSCs-derived exosomes effect was significantly reversed with knockdown of hsa-miR-124-5p (P < 0.0001 vs. NC by WB). CONCLUSIONS BMSCs-derived exosomes suppress cell proliferation and cycle progression and promote cell apoptosis in KG-1a cells, likely acting through hsa-miR-124-5p. Our study establishes a basis for a BMSCs-derived exosomes-based AML treatment.
Apoptosis/genetics* ; Cell Proliferation/genetics* ; Exosomes/genetics* ; Humans ; Leukemia, Myeloid, Acute/genetics* ; Mesenchymal Stem Cells ; MicroRNAs/genetics*

Near infrared spectroscopy combined with chemometrics methods was used to distinguish Ganoderma lucidum samples collected from different origins, and a prediction model was established for rapid determine polysaccharides contents in these samples. The classification accuracy for training dataset was 96.87%, while for independent dataset was 93.33%; as for the prediction model, 5-fold cross-validation was used to optimize the parameters, and different signal processing methods were also optimized to improve the prediction ability of the model. The best square of correlation coefficients for training dataset was 0.965 4, and 0.851 6 for validation dataset; while the root-mean-square deviation values for training dataset and validation dataset were 0.018 5 and 0.023 6, respectively. These results showed that combining near infrared spectroscopy with suitable chemometrics approaches could accuracy distinguish different origins of G. lucidum samples; the established prediction model could precious predict polysaccharides contents, the proposed method can help determine the activity compounds and quality evaluation of G. lucidum.
Fungal Polysaccharides ; analysis ; Geography ; Least-Squares Analysis ; Reishi ; chemistry ; Spectroscopy, Near-Infrared

To observe the effect of Xinfeng Capsules on rheumatoid arthritis (RA) B lymphocytes,inflammatory mediators,FAK/CAPN/PI3K pathway,in order to explore the mechanism of Xinfeng Capsules in improving clinical symptoms of RA.Joint and systemic symptoms of RA patients were observed,and laboratory indicators[hemoglobin (HGB),platelet count (PLT),erythrocyte sedimentation (ESR),immunoglobulin (Ig) G,Ig A,Ig M,rheumatoid factor (RF),anti-cyclic citrulline antibody (CCP-AB),C-reactive protein (CRP)]were detected.ELISA was used to detect serum interleukin (IL)-1β，IL-10,IL-33,chemokine 5 (CCL5),and vascular endothelial growth factor (VEGF).CD3~-CD19~+B cells were measured by flow cytometry.Western blot was used to detect FAK,p-FAK,CAPN,PI3K protein.The results showed that Xinfeng Capsules could significantly alleviate RA joint and systemic symptoms and improve clinical efficacy.And Xinfeng Capsules could increase HGB,decrease PLT,CCP-AB,CRP,ESR index,upregulate IL-10 expression,and down-regulate IL-1β，IL-33,CCL5,VEGF,CD3~-CD19~+B cells,FAK,p-FAK,CAPN,PI3K expressions (P<0.01).Based on the above results,Xinfeng Capsules may reduce the expression of CD3~-CD19~+,regulate the balance of inflammatory cytokines and chemokines,inhibit abnormal activation of FAK/CAPN/PI3K pathway,and improve clinical symptoms of RA.
Arthritis, Rheumatoid/drug therapy* ; B-Lymphocytes ; Capsules ; Drugs, Chinese Herbal ; Humans ; Phosphatidylinositol 3-Kinases ; Vascular Endothelial Growth Factor A

Background: Human infections with zoonotic coronaviruses (CoVs), including severe acute respiratory syndrome (SARS)-CoV and Middle East respiratory syndrome (MERS)-CoV, have raised great public health concern globally. Here, we report a novel bat-origin CoV causing severe and fatal pneumonia in humans. Methods: We collected clinical data and bronchoalveolar lavage (BAL) specimens from five patients with severe pneumonia from Jin Yin-tan Hospital, Wuhan, Hubei province, China. Nucleic acids of the BAL were extracted and subjected to next-generation sequencing. Virus isolation was carried out, and maximum-likelihood phylogenetic trees were constructed. Results: Five patients hospitalized from December 18 to December 29, 2019 presented with fever, cough, and dyspnea accompanied by complications of acute respiratory distress syndrome. Chest radiography revealed diffuse opacities and consolidation. One of these patients died. Sequence results revealed the presence of a previously unknown β-CoV strain in all five patients, with 99.8–99.9% nucleotide identities among the isolates. These isolates showed 79.0% nucleotide identity with the sequence of SARS-CoV (GenBank NC_004718) and 51.8% identity with the sequence of MERS-CoV (GenBank NC_019843). The virus is phylogenetically closest to a bat SARS-like CoV (SL-ZC45, GenBank MG772933) with 87.6–87.7% nucleotide identity, but is in a separate clade. Moreover, these viruses have a single intact open reading frame gene 8, as a further indicator of bat-origin CoVs. However, the amino acid sequence of the tentative receptor-binding domain resembles that of SARS-CoV, indicating that these viruses might use the same receptor. Conclusion: A novel bat-borne CoV was identified that is associated with severe and fatal respiratory disease in humans.

BACKGROUND: Human infections with zoonotic coronaviruses (CoVs), including severe acute respiratory syndrome (SARS)-CoV and Middle East respiratory syndrome (MERS)-CoV, have raised great public health concern globally. Here, we report a novel bat-origin CoV causing severe and fatal pneumonia in humans. METHODS: We collected clinical data and bronchoalveolar lavage (BAL) specimens from five patients with severe pneumonia from Wuhan Jinyintan Hospital, Hubei province, China. Nucleic acids of the BAL were extracted and subjected to next-generation sequencing. Virus isolation was carried out, and maximum-likelihood phylogenetic trees were constructed. RESULTS: Five patients hospitalized from December 18 to December 29, 2019 presented with fever, cough, and dyspnea accompanied by complications of acute respiratory distress syndrome. Chest radiography revealed diffuse opacities and consolidation. One of these patients died. Sequence results revealed the presence of a previously unknown β-CoV strain in all five patients, with 99.8% to 99.9% nucleotide identities among the isolates. These isolates showed 79.0% nucleotide identity with the sequence of SARS-CoV (GenBank NC_004718) and 51.8% identity with the sequence of MERS-CoV (GenBank NC_019843). The virus is phylogenetically closest to a bat SARS-like CoV (SL-ZC45, GenBank MG772933) with 87.6% to 87.7% nucleotide identity, but is in a separate clade. Moreover, these viruses have a single intact open reading frame gene 8, as a further indicator of bat-origin CoVs. However, the amino acid sequence of the tentative receptor-binding domain resembles that of SARS-CoV, indicating that these viruses might use the same receptor. CONCLUSION A novel bat-borne CoV was identified that is associated with severe and fatal respiratory disease in humans.
Adult ; Aged ; Betacoronavirus ; genetics ; isolation & purification ; Coronavirus Infections ; diagnostic imaging ; therapy ; virology ; Female ; Humans ; Male ; Middle Aged ; Pandemics ; Pneumonia, Viral ; diagnostic imaging ; therapy ; virology ; Tomography, X-Ray ; Treatment Outcome