As the core technology of processing， the stir-frying method of traditional Chinese medicine（TCM） realizes the regulation of efficacy of medicinal substances through the coordination of fire gradient and excipients. This study aims to systematically analyze the influence of different stir-frying degrees（stir-frying until yellow， stir-frying to brown， stir-frying to charcoal） and excipient types（solid excipients such as rice， wheat bran， soil， liquid excipients such as rice wine， vinegar， honey） on the physicochemical properties， efficacy and toxicity of TCM， summarizing their common regulatory mechanisms and characteristics. Then， the three-dimensional regulatory common mechanisms and five-dimensional regulatory specificity mechanisms of different stir-frying processes were obtained. The three-dimensional regulatory common mechanisms are as follows：①Thermal effects break down inherent barriers of medicinal materials and improve the dissolution of components. ②Inducing Maillard reaction， carbonization and other reactions of medicinal materials to promote the transformation of components. ③Combining the catalytic and harmonizing effects of excipients to achieve targeted enrichment of efficacious substances and precise control of toxic components. The five-dimensional regulatory specificity mechanisms manifest as：①The efficacy gradient pattern where stir-frying until yellow strengthens the spleen， stir-frying to brown aids digestion， and stir-frying to charcoal stops bleeding. ②According to the polarity difference and intrinsic properties， the liquid excipients form a directional synergistic mechanism of wine processing enhances ascending nature， ginger processing to warm and disperse， salt processing directs effects to the kidneys， vinegar processing targets the liver， honey processing imparts sweetness and moderation. ③Through porous structure and interfacial properties， solid excipients give the synergistic effect of rice processing for diarrhea relief， bran processing for stomach tonification， soil processing for warming the middle warmer， and clam powder/talcum powder/sand processing for texture optimization. ④Thermal effects induce decomposition/oxidation/polymerization and other reactions to reshape the material basis， directing changes in the efficacy. ⑤The targeted distribution of efficacy is regulated by component enrichment and meridian-guiding effect， and the meridian tropism is changed. The system， driven by thermal effect， excipient synergy and physicochemical reconstruction， integrates five-dimensional regulation of fire， solvent， interface， composition and distribution. It systematically explains the inherent law of efficacy-substance-process of traditional stir-frying， and provides theoretical basis and practical guidance for standardizing TCM processing and enhancing the efficacy.

Objective To analyze the core functional component groups(CFCG)in Yinchenhao Decoction(YCHD)and their possible pathways for treating hepatic fibrosis based on network pharmacology.Methods PPI data were extracted from DisGeNET,Genecards,CMGRN and PTHGRN to construct a weighted network using Cytoscape 3.9.1.The data of the chemical components in YCHD were obtained from Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP),and the potential active components and targets were selected using PreADMET Web server and SwissTargetPrediction.A fusion model was constructed to obtain the functional effect space and evaluate the effective proteins to identify the CFCG followed by GO and KEGG pathway enrichment analyses for all the targets.In cultured human hepatic stellate cells(LX-2 cells),the cytotoxicity of different compounds in YCHD was tested using CCK-8 assay;the effects of these compounds on collagen α1(Col1a1)mRNA expression and the pathways in 20 ng/mL TGF-β1-stimulated cells were analyzed using RT-qPCR and Western blotting.Results A total of 1005 pathogenic genes,226 potential active components and 1529 potential targets in YCHD and 52 potential targets of CFCG were obtained.Benzyl acetate,vanillic acid,clorius,polydatin,lauric acid and ferulic acid were selected for CCK-8 verification,and they all showed minimal cytotoxicity below the concentration of 200 μmol/L.Clorius,polydatin,lauric acid and ferulic acid all effectively inhibited TGF-β1-induced LX-2 cell activation.At the concentration of 200 μmol/L,all these 4 components inhibited PI3K,p-PI3K,AKT,p-AKT,ERK,p-ERK,P38 MAPK and p-P38 MAPK expressions in TGF-β1-induced LX-2 cells.Conclusion The therapeutic effect of YCHD on hepatic fibrosis is probably mediated by its core functional components including benzyl acetate,vanillic acid,clorius,polydatin,lauric acid and ferulic acid,which inhibit the PI3K-AKT and MAPK pathways in hepatic stellate cells.

Chronic kidney disease(CKD)often begins subtly,with its prevalence steadily rising over time,some patients may already be in end-stage renal disease by the time they seek treatment,making it a signifi-cant global public health concern.Early and prompt diagnosis and treatment are crucial in slowing disease ad-vancement,enhancing patients'quality of life,and ultimately improving prognosis.Current studies have shown that hypoxia,directly or indirectly induced,is an important pathological mechanism in the occurrence and de-velopment of CKD,and hypoxia inducible factor-1α(HIF-1α)is one of the main nuclear transcription factors in the body's response to hypoxia.It plays an important role in the occurrence and development of kidney dis-eases in the process of energy metabolism,angiogenesis,apoptosis,tissue inflammation and fibrosis.There-fore,this article briefly reviews the research progress of HIF-1α in CKD,and provides more effective strategies for the prevention and treatment of CKD.

Objective To analyze the core functional component groups(CFCG)in Yinchenhao Decoction(YCHD)and their possible pathways for treating hepatic fibrosis based on network pharmacology.Methods PPI data were extracted from DisGeNET,Genecards,CMGRN and PTHGRN to construct a weighted network using Cytoscape 3.9.1.The data of the chemical components in YCHD were obtained from Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP),and the potential active components and targets were selected using PreADMET Web server and SwissTargetPrediction.A fusion model was constructed to obtain the functional effect space and evaluate the effective proteins to identify the CFCG followed by GO and KEGG pathway enrichment analyses for all the targets.In cultured human hepatic stellate cells(LX-2 cells),the cytotoxicity of different compounds in YCHD was tested using CCK-8 assay;the effects of these compounds on collagen α1(Col1a1)mRNA expression and the pathways in 20 ng/mL TGF-β1-stimulated cells were analyzed using RT-qPCR and Western blotting.Results A total of 1005 pathogenic genes,226 potential active components and 1529 potential targets in YCHD and 52 potential targets of CFCG were obtained.Benzyl acetate,vanillic acid,clorius,polydatin,lauric acid and ferulic acid were selected for CCK-8 verification,and they all showed minimal cytotoxicity below the concentration of 200 μmol/L.Clorius,polydatin,lauric acid and ferulic acid all effectively inhibited TGF-β1-induced LX-2 cell activation.At the concentration of 200 μmol/L,all these 4 components inhibited PI3K,p-PI3K,AKT,p-AKT,ERK,p-ERK,P38 MAPK and p-P38 MAPK expressions in TGF-β1-induced LX-2 cells.Conclusion The therapeutic effect of YCHD on hepatic fibrosis is probably mediated by its core functional components including benzyl acetate,vanillic acid,clorius,polydatin,lauric acid and ferulic acid,which inhibit the PI3K-AKT and MAPK pathways in hepatic stellate cells.

Objective Taking 41 kinds of Chinese herbal medicines commonly used in Meizhou Hakka as the research object,their inhibitory activities against α-glucosidase and α-amylase were screened and the enzyme inhibition types of the species with the strongest activities were explored.Methods The inhibitory activities of 41 commonly used Hakka herbs in Meizhou against α-glucosidase and α-amylase were evaluated by the p-Nitrophenyl a-D-mannopyranoside(pNPG)method and the 3,5-Dinitrosalicylic acid(DNS)method,using the inhibitory rate of half(IC50)as an index.The inhibitory activity of 95%ethanol extracts of 41 Chinese herbal medicines commonly used in Meizhou Hakka on α-glucosidase and α-amylase were analysed.The enzymatic kinetics method and Lineweaver-Burk curve were used to analyze the inhibitory type of the most active species.Results The results showed that 40 Chinese herbal medicines commonly used in Meizhou Hakka had α-glucosidase inhibitory activity,and 23 medicines had α-amylase inhibitory activity,among which Psychotria asiatica Wall.showed the strongest inhibitory activity with the IC50 values aganist α-glucosidase and α-amylase of 0.17±0.001 mg·mL-1 and 0.09±0.001 mg·mL-1,respectively.The inhibition types were reversible competitive inhibition and reversible non-competitive inhibition,respectively.Conclusion The Psychotria asiatica Wall.Chinese herbal medicines commonly used in Meizhou Hakka has significant inhibitory effect on the activity of glucose metabolism enzymes,which has potential value for further research and development on the prevention and treatment of diabetes mellitus.

Objective:To evaluate the feasibility of PET automatic drug infusion system combined with power peripherally inserted central catheter (PICC) for 18F-FDG injection and PET/CT imaging. Methods:Fifty patients with malignant neoplasms who underwent 18F-FDG PET/CT imaging in Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine between December 2021 to July 2022 were prospectively enrolled. They were equally divided into power PICC group and peripheral venipuncture group. PET automatic drug infusion system was respectively connected with the pre-established channels of power PICC and peripheral venipuncture for 18F-FDG injection. Each patient underwent a routine PET/CT imaging at 1 h post-injection. The blood glucose, body weight, prescription dose and injection dose were recorded, and SUV max in the liver and cavoatrial junction were measured in both groups. The independent-sample t test was performed to compare the differences between 2 groups. The power PICC tip positions after 18F-FDG injection in power PICC group were observed. Results:The liver SUV max in the power PICC group and peripheral group were 2.54±0.50 and 2.57±0.31 ( t=0.37, P=0.716), and the SUV max of cavoatrial junction in the 2 groups were 1.68±0.25 and 1.63±0.22 ( t=-0.78, P=0.441), respectively. No significant differences were found in blood glucose, body weight, prescription dose and injection dose between the 2 groups ( t values: 0.00-0.13, all P>0.05). The ratios of injection dose to prescription dose in the 2 groups were 0.998 3±0.007 3 and 0.997 6±0.016 5, respectively, indicating high injection accuracy of the injection methods. No obvious drug residue was displayed at the end of catheter, resulting in good imaging quality. All the tip positions after injection were between T5 and T8, in line with the standardization management of power PICC. Conclusion:PET automatic drug infusion system combined with power PICC can be safely used for 18F-FDG injection and PET/CT imaging with less injection puncture.

In recent years, the problem of bacterial resistance has become more and more serious, which has brought troubles to global public health and medical care. The time and money required to develop new antibiotics is even greater than before. Bacteriophage is a kind of virus that can specifically infect bacteria, fungi, actinomycetes and other microorganisms. Relying on host bacteria to replicate in large numbers, rich species, low research and development cost, the value of anti-infection therapy is very considerable. It is a new generation of biological antimicrobial agents with great potential. This paper briefly describes the sterilization mechanism, progress of research on anti-infection aspect and clinical application of phage, in order to provide reference for phage anti-infection treatment and clinical application.

Chimeric antigen receptor T (CAR-T) cell therapy is a novel cellular immunotherapy that is widely used to treat hematological malignancies, including acute leukemia, lymphoma, and multiple myeloma. Despite its remarkable clinical effects, this therapy has side effects that cannot be underestimated. Cytokine release syndrome (CRS) is one of the most clinically important and potentially life-threatening toxicities. This syndrome is a systemic immune storm that involves the mass cytokines releasing by activated immune cells. This phenomenon causes multisystem damages and sometimes even death. In this study, we reported the management of a patient with recurrent and refractory multiple myeloma and three patients with acute lymphocytic leukemia who suffered CRS during CAR-T treatment. The early application of tocilizumab, an anti-IL-6 receptor antibody, according to toxicity grading and clinical manifestation is recommended especially for patients who suffer continuous hyperpyrexia, hypotensive shock, acute respiratory failure, and whose CRS toxicities deteriorated rapidly. Moreover, low doses of dexamethasone (5-10 mg/day) were used for refractory CRS not responding to tocilizumab. The effective management of the toxicities associated with CRS will bring additional survival opportunities and improve the quality of life for patients with cancer.

OBJECTIVETo report on the result of thalassemia screening and genetic diagnosis for pregnant women from Guiyang region.

METHODSPrenatal screening for thalassemia was carried out based on erythrocyte parameters and hemoglobin electrophoresis. Single-tube multiplex GAP-PCR and PCR-reverse dot blot hybridization were performed on suspected cases to identify common alpha- and beta- thalassemia mutations, and direct sequencing was used for identifying rare mutations.

RESULTSAmong 13 738 pregnant women, 1745 (12.70%) were suspected as thalassemia. In terms of native place, the provinces with highest screening-positive rates were Guangxi, Guangdong, Jiangxi and Guizhou. And the ethnic groups with highest screening-positive rates were Zhuang, Li, and Buyi. Among 801 women subjected to genetic testing, 457 (57.05%) were diagnosed with thalassemia. In total 9 genotypes of alpha- thalassemia were detected, with the most common genotypes being --/alpha alpha (63.35%), - alpha/alpha alpha (19.37%) and - alpha/alpha alpha (8.90%). Eleven genotypes of beta- thalassemia were detected, with the most common genotypes being CD17/N (42.91%), CD41-42/N (32.46%) and IVS-II-654/N (11.94%). Two cases were detected with rare beta-thalassemia mutations (CD54-58/N and IVS-I-130/N).

CONCLUSIONThe screening-positive rate of thalassemia among pregnant women in Guiyang region is relatively high. The rates have shown substantial difference in terms of native place and ethnic group. Thalassemia-related mutations in Guizhou region have a diverse spectrum, which showed certain difference from those of other regions.

Adolescent ; Adult ; Female ; Genotype ; Humans ; Middle Aged ; Pregnancy ; Prenatal Diagnosis ; methods ; Thalassemia ; genetics ; Young Adult

PURPOSE: MicroRNAs (miRs) were recently recognized to be important for immune cell differentiation and immune regulation. However, whether miRs were involved in allergen-specific immunotherapy (SIT) remains largely unknown. This study sought to examine changes in miR-146a and T regulatory cells in children with persistent allergic rhinitis (AR) after 3 months of subcutaneous immunotherapy (SCIT) and sublingual immunotherapy (SLIT). METHODS: Twenty-four HDM-sensitized children with persistent AR were enrolled and treated with SCIT (n=13) or SLIT (n=11) for 3 months. Relative miR-146a and Foxp3 mRNA expression, the TRAF6 protein level, and the ratio of post-treatment to baseline IL-10+CD4+ T cells between the SCIT and SLIT groups were examined in the peripheral blood mononuclear cells (PBMCs) of AR patients using quantitative reverse transcription polymerase chain reaction (qRT-PCR), flow cytometry, and Western blot analysis, respectively. Serum levels of IL-5 and IL-10 were determined using ELISA. RESULTS: After 3 months of SIT, both the TNSS and INSS scores were significantly decreased compared to the baseline value (P<0.01). The relative expression of miR-146a and Foxp3 mRNA was significantly increased after both SCIT and SLIT (P<0.01). The ratio of post-treatment to baseline IL-10+CD4+ T cells and the serum IL-10 level were significantly increased in both the SCIT and SLIT groups (P<0.01), whereas the TRAF6 protein level and serum IL-5 level were significantly decreased (P<0.01). No significant differences in these biomarkers were observed between the SCIT and SLIT groups. CONCLUSIONS: Our findings suggest that miR-146a and its related biomarkers may be comparably modulated after both SCIT and SLIT, highlighting miR-146a as a potential therapeutic target for the improved management of AR.
Biomarkers ; Blotting, Western ; Cell Differentiation ; Child* ; Enzyme-Linked Immunosorbent Assay ; Flow Cytometry ; Humans ; Immunotherapy* ; Interleukin-10 ; Interleukin-5 ; MicroRNAs ; Polymerase Chain Reaction ; Reverse Transcription ; Rhinitis* ; RNA, Messenger ; Sublingual Immunotherapy ; T-Lymphocytes ; TNF Receptor-Associated Factor 6