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BACKGROUND: Fanlian Huazhuo Formula (FLHZF) has the functions of invigorating spleen and resolving phlegm, clearing heat and purging turbidity. It has been identified to have therapeutic effects on type 2 diabetes mellitus (T2DM) in clinical application. Non-alcoholic fatty liver disease (NAFLD) is frequently diagnosed in patients with T2DM. However, the therapeutic potential of FLHZF on NAFLD and the underlying mechanisms need further investigation. AIM: To elucidate the effects of FLHZF on NAFLD and explore the underlying hepatoprotective mechanisms in vivo and in vitro. METHODS: HepG2 cells were treated with free fatty acid for 24 hours to induce lipid accumulation cell model. Subsequently, experiments were conducted with the different concentrations of freeze-dried powder of FLHZF for 24 hours. C57BL/6 mice were fed a high-fat diet for 8-week to establish a mouse model of NAFLD, and then treated with the different concentrations of FLHZF for 10 weeks. RESULTS: FLHZF had therapeutic potential against lipid accumulation and abnormal changes in biochemical indicators in vivo and in vitro. Further experiments verified that FLHZF alleviated abnormal lipid metabolism might by reducing oxidative stress, regulating the AMPKα/SREBP-1C signaling pathway, activating autophagy, and inhibiting hepatocyte apoptosis. CONCLUSION: FLHZF alleviates abnormal lipid metabolism in NAFLD models by regulating reactive oxygen species, autophagy, apoptosis, and lipid synthesis signaling pathways, indicating its potential for clinical application in NAFLD.
Subject(s)
Autophagy , Diet, High-Fat , Disease Models, Animal , Drugs, Chinese Herbal , Lipid Metabolism , Mice, Inbred C57BL , Non-alcoholic Fatty Liver Disease , Oxidative Stress , Signal Transduction , Non-alcoholic Fatty Liver Disease/drug therapy , Non-alcoholic Fatty Liver Disease/metabolism , Non-alcoholic Fatty Liver Disease/pathology , Non-alcoholic Fatty Liver Disease/etiology , Animals , Autophagy/drug effects , Diet, High-Fat/adverse effects , Humans , Drugs, Chinese Herbal/pharmacology , Drugs, Chinese Herbal/therapeutic use , Signal Transduction/drug effects , Hep G2 Cells , Mice , Male , Oxidative Stress/drug effects , Lipid Metabolism/drug effects , Liver/drug effects , Liver/pathology , Liver/metabolism , Lipogenesis/drug effects , Hepatocytes/drug effects , Hepatocytes/metabolism , Hepatocytes/pathologyABSTRACT
BACKGROUND: Preserving laryngeal function and reconstructing the hypopharynx in advanced hypopharyngeal cancer pose significant challenges for head and neck surgeons. METHODS: A 48-year-old male patient was diagnosed with advanced hypopharyngeal cancer originating from the left pyriform sinus. The tumor extended into the hypopharynx, left vocal cord, ventricular fold, partial aryepiglottic fold, and a segment of the cervical esophagus. A curative tumor resection was performed, and a well-thought-out strategy was employed for hypopharyngeal repair and laryngeal reconstruction. RESULTS: Following the surgery, the patient demonstrated exceptional flap survival, and the tracheostomy tube was removed at the 6-month mark. No surgery-related complications were observed, and both swallowing and vocal functions exhibited a robust recovery. CONCLUSION: Our reconstruction strategy proves effective in preserving laryngeal function among patients with advanced hypopharyngeal cancer.
Subject(s)
Hypopharyngeal Neoplasms , Larynx , Plastic Surgery Procedures , Male , Humans , Middle Aged , Hypopharyngeal Neoplasms/surgery , Hypopharyngeal Neoplasms/pathology , Hypopharynx/surgery , Hypopharynx/pathology , Surgical Flaps/pathology , Larynx/pathologyABSTRACT
Photodynamic therapy has emerged as a recognized anti-tumor treatment involving three fundamental elements: photosensitizers, light, and reactive oxygen species. Enhancing the effectiveness of photosensitizers remains the primary avenue for improving the biological therapeutic outcomes of PDT. Through three generations of development, HPPH is a 2-(1-hexyloxyethyl)-2-devinyl derivative of pyropheophorbide-α, representing a second-generation photosensitizer already undergoing clinical trials for various tumors. The evolution toward third-generation photosensitizers based on HPPH involves structural modifications for multimodal applications and the combination of multifunctional compounds, leading to improved imaging localization and superior anti-tumor effects. While research into third-generation HPPH is beneficial for advancing PDT treatment, equal attention should also be directed toward the other two essential elements and personalized diagnosis and treatment methodologies.
Subject(s)
Neoplasms , Photochemotherapy , Humans , Photosensitizing Agents/therapeutic use , Photochemotherapy/methods , Neoplasms/drug therapy , Chlorophyll/pharmacologyABSTRACT
Purulent chondritis of the thyroid cartilage is a rare affliction that is not frequently observed in patients undergoing laryngeal surgery. The formation of abscesses between the inner and outer perichondria can cause constriction of the laryngeal lumen, leading to hoarseness and difficulty breathing. This report details the case of a middle-aged diabetic woman who experienced swelling in the tissue of her laryngeal cavity and destruction of her thyroid cartilage plate after undergoing laryngectomy. The pathological examination revealed evidence of inflammation, and the patient was ultimately diagnosed with purulent chondritis of the thyroid cartilage.
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Background: Diabetes mellitus brings serious threats and financial burdens to human beings worldwide. Fufang Fanshiliu decoction (FFSLD), a traditional Chinese medicine formula showing great antidiabetic effects, has been used in clinics for many years. Objective: This study aims to explore the underlying therapeutic mechanisms of FFSLD in Type II diabetes mellitus (T2DM). Methods: Sprague-Dawley rats induced by high-fat diet feeding combined with streptozotocin injection were used to establish the T2DM model. All rats were randomly divided into 6 groups: control, model, metformin, high dosage, middle dosage, and low dosage of FFSLD. After 4 weeks of treatment, serum, intestinal mucosa, and fecal samples were collected for further analysis. ELISA was used to detect the diabetic-related serum indicators and proinflammation cytokines. Gene or protein expressions of mitogen-activated protein kinase (MAPK), interleukin 1 beta (IL-1ß), transforming growth factor-beta (TGF-ß), and tumor necrosis factor-alpha (TNF-α) in intestinal mucosa were analyzed by quantitative real-time polymerase chain reaction (RT-PCR) or western blot. 16s rRNA gene sequencing was used to detect the changes of gut microbiome in these groups. Intestinal gut microbiota (GM) composition was further analyzed according to the sequencing libraries. Results: FFSLD effectively recovered the diabetic-related biochemical indexes by reducing fasting blood glucose (FBG), total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), insulin, and increasing high-density lipoprotein cholesterol (HDL-C). Furthermore, FFSLD significantly ameliorated the abnormal levels of proinflammation cytokines including IL-1ß, IL-6, TNF-α, and TGF-ß. In addition, the GM compositions of rats in control, model, and FFSLD treated groups were different. FFSLD significantly increased the relative abundance of Lactobacillus, Akkermansia, and Proteus, and reduced the relative abundance of Alistipes, Desulfovibrio, and Helicobacter. Moreover, these changed bacteria were closely related to the diabetic-related serum indicators and proinflammatory cytokines. Conclusion: These results suggest that FFSLD alleviates diabetic symptoms in T2DM rats through regulating GM composition and inhibiting inflammatory response, which clarify the therapeutic mechanism of FFSLD on T2DM and provide a theoretical basis for its further clinical application.
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BACKGROUND: 17α-Hydroxylase deficiency (17-OHD) is a rare form of congenital adrenal hyperplasia, characterized by hypertension, hypokalemia, and gonadal dysplasia. However, due to the lack of a comprehensive understanding of this disease, it is prone to misdiagnosis and missed diagnosis, and there is no complete cure. CASE SUMMARY: We report a female patient with 17-OHD. The patient was admitted to the Department of Neurology of our hospital due to limb weakness. During treatment, it was found that the patient's condition was difficult to correct except for hypokalemia, and her blood pressure was difficult to control with various antihypertensive drugs. She was then transferred to our department for further treatment. On physical examination, the patient's gonadal development was found to be abnormal, and chromosome analysis demonstrated karyotype 46,XY. Considering the possibility of 17-OHD, the cytochrome P450 family 17 subfamily A member 1 (CYP17A1) test was performed to confirm the diagnosis. CONCLUSION: The clinical manifestations of 17-OHD are complex. Hormone determination, imaging examination, chromosome determination and CYP17A1 gene test are helpful for early diagnosis.
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ETHNOPHARMACOLOGICAL RELEVANCE: Fufang Fanshiliu decoction (FFSLD) is a Chinese herbal medicine prescription that has been used in type 2 diabetes mellitus (T2DM), while the underlying mechanism remains unclear. AIM OF THE STUDY: To validate the efficacy and explore the potential mechanisms of FFSLD in treating T2DM via integrating a network pharmacological approach and experimental evaluation. MATERIALS AND METHODS: T2DM mice model induced by high-fat diet feeding combined with streptozotocin injection was selected to investigate the alleviation of FFSLD against T2DM, via detecting the levels of glucose, insulin, glucagon (GC), triglyceride (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C). Network pharmacological analysis was used to predict the potential mechanisms, including the pharmacokinetics and drug-likeness screening, active ingredients and potential targets prediction, network analysis, and enrichment analysis. The candidate bioactive molecules of FFSLD, and targets information excavated through TCMSP, Uniprot, GeneCards, OMIM databases, were combined for comprehensive analysis by constructing "drug-compound-target-disease" and "protein-protein interaction" networks. Enrichment analysis was performed via Gene Ontology (GO) and Koto Encyclopedia of Genes and Genomes (KEGG) databases. HepG2 insulin-resistance (IR) cells model induced by high glucose was used to verify the potential mechanisms of FFSLD against T2DM which were predicted by the network pharmacology. RESULTS: The animal study showed that FFSLD significantly decreased the blood glucose, and reversed the abnormal levels of insulin, GC, TG, TC, HDL-C, and LDL-C in T2DM mice. Network pharmacological analysis indicated that 106 active compounds of FFSLD might be correlated with 628 targets in treating T2DM, and the mechanism would probably be related to insulin resistance that harbored a high response value (P = 5.88844 E-33) though regulating Akt1, ESR1, oxidoreductase activity, and JAK/STAT signalings. Experimental validation showed that FFSLD reduced the ROS level, up-regulated the expressions of p-AKT, Nrf-2, and ESR1, and down-regulated the expressions of JAK2, STAT3, and Keap-1 in the HepG2-IR cells model. CONCLUSIONS: This study demonstrated that the therapeutic effect of FFSLD on T2DM was related to IR alleviation. The underlying mechanisms were associated with the regulation of PI3K/AKT, JAK/STAT, oxidative stress, and ESR signaling pathways.
Subject(s)
Diabetes Mellitus, Type 2 , Drugs, Chinese Herbal , Insulin Resistance , Animals , Cholesterol, LDL , Diabetes Mellitus, Type 2/metabolism , Drugs, Chinese Herbal/pharmacology , Drugs, Chinese Herbal/therapeutic use , Glucose , Insulin , Mice , Phosphatidylinositol 3-Kinases/metabolism , Proto-Oncogene Proteins c-akt/metabolismABSTRACT
Background: Increasing evidence has suggested an association of adiponectin gene polymorphisms rs1501299, rs2241766, rs266729 and rs3774261 with risk of nonalcoholic fatty liver disease (NAFLD). This correlation has been extensively meta-analyzed for the first two polymorphisms, but not the second two. Methods: The PubMed, EMBASE, Google Scholar, and China National Knowledge Infrastructure databases were searched for relevant literature. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated. Results: A total of 10 case-control studies on rs266729 (2,619 cases and 1,962 controls) and 3 case-control studies on rs3774261 (562 cases and 793 controls) were included. Meta-analysis showed that rs266729 was associated with significantly higher NAFLD risk based on the following five models: allelic, OR 1.72, 95% CI 1.34-2.21, P < 0.001; recessive, OR 2.35, 95% CI 1.86-2.95, P < 0.001; dominant, OR 1.84, 95% CI 1.34-2.53, P < 0.001; homozygous, OR 2.69, 95% CI 1.84-3.92, P < 0.001; and heterozygous, OR 1.72, 95% CI 1.28-2.32, P < 0.001. This association between rs266729 and NAFLD risk remained significant for all five models among studies with Asian, Chinese and Caucasian samples. The rs2241766 polymorphism was associated with significantly higher NAFLD risk according to the recessive model (OR 1.87, 95% CI 1.15-3.04, P = 0.01). Conclusion: Polymorphisms rs266729 and rs3774261 in the adiponectin gene may be risk factors for NAFLD. These findings may pave the way for novel therapeutic strategies, but they should be verified in large, well-designed studies.
Subject(s)
Adiponectin , Non-alcoholic Fatty Liver Disease , Adiponectin/genetics , Alleles , Asian People/genetics , Humans , Non-alcoholic Fatty Liver Disease/genetics , Polymorphism, Single NucleotideABSTRACT
Osteoporosis (OP) is one of the most common bone diseases, especially in women after menopause. Increasing evidence shows that non-coding RNAs are implicated in the pathogenesis of OP. In this study, based on the published circular RNA profiling data between OP patients and healthy controls, we found that circRNA_0001795 (circ_0001795) is downregulated in OP samples, which was further validated in the OP samples collected in this study. We therefore investigated the functional role and molecular mechanism of circ_0001795 in the osteogenic differentiation of human bone marrow stromal cells (hBMSCs) hBMSCs by alkaline phosphatase (ALP) activity assay, ALP and Alizarin Red S (ALS) Staining, luciferase reporter assay. Our data revealed that the overexpression of circ_0001795 could significantly promote the osteogenic differentiation of hBMSCs. MiRNA-339-5p (miR-339-5p) was identified as a target of circ_0001795, and miR-339-5p mimic attenuated the effect of circ_0001795 overexpression. MiR-339-5p downregulated yes-associated protein 1 (YAP1), which mediates the effect of circ_0001795 overexpression. Overall, this study uncovered the role of circ_0001795/miR-339-5p/YAP1 axis in regulating osteogenic differentiation, indicating that targeting Circ_0001795 could serve as a novel therapeutic target for OP.
Subject(s)
Gene Expression Regulation , Mesenchymal Stem Cells/metabolism , MicroRNAs/biosynthesis , Osteoporosis/metabolism , RNA, Circular/metabolism , YAP-Signaling Proteins/biosynthesis , Aged , Cells, Cultured , Female , Humans , Male , MicroRNAs/genetics , Middle Aged , Osteoporosis/genetics , RNA, Circular/genetics , YAP-Signaling Proteins/geneticsABSTRACT
BACKGROUND: Diabetic coronary heart disease (DCHD), the main macrovascular complication of type 2 diabetes mellitus (T2DM), is greatly harmful to T2DM patients. Traditional Chinese medicine (TCM) is an alternative and effective therapy to delay the development of macrovascular diseases, but the existing evidence of its efï¬cacy and safety is insufï¬cient. The aim of this multicenter, randomized, double-blind, placebo-controlled trial is to evaluate the efï¬cacy and safety of Chinese Medicine Fufang Zhenzhu Tiaozhi capsule (FTZ) in treating DCHD. PATIENTS AND METHODS: This study includes a 2-week run-in, 52-week treatment, and 52-week post-treatment follow-up. A total of 160 participants will be recruited and randomized into two groups. The treatment group will receive FTZ and basic treatment, while the control group will receive the placebo and basic treatment. The primary outcome is the combined outcome including the major adverse cardiovascular events, coronary restenosis, and unplanned revascularization. The combined secondary outcomes include all-cause mortality, acute coronary syndrome, ischemic stroke, heart failure, unplanned re-hospitalization mainly caused by acute complications of diabetes, other thromboembolic events, and TCM symptom indicators. The safety outcomes and adverse events will also be evaluated in this trial. DISCUSSION: This trial evaluates the clinical effectiveness and safety of FTZ in patients with DCHD. The results are important to further explore the effectiveness of the comprehensive strategy "Tiao Gan Qi Shu Hua Zhuo" (modulating Gan, trigging key metabolic system to resolve pathogenic factors such as phlegm retention and dampness) in the prevention and control of glucolipid metabolic disorders (GLMD) including DCHD and T2DM. On the other hand, this study is the ï¬rst trial of FTZ to observe cardiovascular outcomes through long-term follow-up after treatment of DCHD, which is of great value. TRIAL REGISTRATION: This trial was registered in the Chinese Clinical Trial Registry on April 07, 2019 (No. ChiCTR1900022345).
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AIMS: Type 2 diabetes is considered to be one of the essential risks of adverse outcomes in coronavirus disease 2019 (COVID-19).1 Metformin and insulin were suggested to affect the outcomes. However, divergent views are still expressed. We aim to gain further insight into metformin and insulin in both pre-admission and in-hospital usage in COVID-19 patients with pre-existed type 2 diabetes. MAIN METHODS: This is a multicentral retrospective study of the hospital confirmed COVID-19 patients between January 19 to April 09, 2020, who admitted to 3 main hospitals in Xiangyang city, China. The effect of type 2 diabetes, metformin, and insulin on COVID-19 were analyzed, respectively. Clinical characteristics, blood laboratory indices, clinical observational indices, and outcomes of these cases were collected. KEY FINDINGS: A total of 407 confirmed COVID-19 patients (including 50 pre-existed type 2 diabetes) were eligible in our study. COVID-19 patients with type 2 diabetes had more adverse outcomes than non-diabetes (OR2: mortality: 1.46 [95% CI3 1.11, 1.93]; P < 0.001). Pre-admission metformin usage showed a declined intensive care unit admission rate in a dose-dependent fashion (OR 0.04 [95% CI 0.00, 0.99]; adjust P = 0.049). While in-hospital insulin usage attempted to increase the invasive ventilation (8 [34.8%] vs. 1 [3.7%], adjust P = 0.043), independent of age and blood glucose. SIGNIFICANCE: Our study indicated that pre-admitted metformin usage may have beneficial effects on COVID-19 with pre-existed type 2 diabetes, insulin should be used sparingly in the hospital stay.
Subject(s)
COVID-19/complications , Diabetes Mellitus, Type 2/drug therapy , Hypoglycemic Agents/therapeutic use , Insulin/therapeutic use , Intensive Care Units/statistics & numerical data , Metformin/therapeutic use , SARS-CoV-2/isolation & purification , Adult , Blood Glucose , COVID-19/transmission , COVID-19/virology , China/epidemiology , Diabetes Mellitus, Type 2/epidemiology , Diabetes Mellitus, Type 2/virology , Female , Hospitalization/statistics & numerical data , Humans , Male , Middle Aged , Retrospective StudiesABSTRACT
INTRODUCTION: The Chinese government has invested US$140 million annually on prevention of mother-to-child transmission (PMTCT) of HIV. This study evaluates the programme by examining the improvements in programme coverage HIV testing and provision of antiviral drugs along the PMTCT cascade. METHODS: Data for PMTCT cascade indicators were collected through a comprehensive systematic review of published peer-reviewed English and Chinese literature during 2003-2011. Meta-analysis was conducted according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. RESULTS: This study included 113 publications. HIV prevalence among pregnant women in China who accessed antenatal care (ANC) remained below 0.1% during the past decade. HIV testing coverage in pregnant women attending ANC and in HIV-exposed infants at 18â months significantly increased from 62.4% (95% CI 4.7% to 98.2%) and 22.1% (16.3% to 32.3%) in 2003 to 90.3% (88.4% to 91.8%) and 82.8% (66.9% to 99.5%) in 2011 respectively, whereas antiretroviral (ARV) prophylaxis uptake increased from 35.2% (12.2% to 47.3%) and 26.9% (24.3% to 28.9%) to 86.2% (53.2% to 97.2%) and 90.3% (85.5% to 93.7%). HIV vertical transmission rate substantially decreased from 31.8% (25.7% to 38.6%) prior to the programme to 2.3% (1.4% to 3.8%) in 2011. During 2003-2011, among 25,312 (23,995-26,644) infants born to HIV-positive mothers who received ARV prophylaxis, 975 (564-1395) were diagnosed with HIV, corresponding to an average transmission rate of 3.9% (3.2% to 4.6%). However, while including transmissions among HIV-positive pregnant women who were lost along the cascade, the average transmission rate during 2003-2011 was 17.4% (15.8% to 19.0%). CONCLUSIONS: PMTCT programmes have reduced HIV mother-to-child transmission in China. Further improvements in the continuum of care remain essential in realising the full potential of the programme.