This study aims to investigate the mechanism of Qingrun Decoction in alleviating hepatic insulin resistance in type 2 diabetes mellitus(T2DM) rats through the reprogramming of amino acid metabolism. A T2DM rat model was established by inducing insulin resistance through a high-fat diet combined with intraperitoneal injection of streptozotocin. The model rats were randomly divided into five groups: model group, high-, medium-, and low-dose Qingrun Decoction groups, and metformin group. A normal control group was also established. The rats in the normal and model groups received 10 mL·kg~(-1) distilled water daily by gavage. The metformin group received 150 mg·kg~(-1) metformin suspension by gavage, and the Qingrun Decoction groups received 11.2, 5.6, and 2.8 g·kg~(-1) Qingrun Decoction by gavage for 8 weeks. Blood lipid levels were measured in different groups of rats. Pathological damage in rat liver tissue was assessed by hematoxylin-eosin(HE) staining and oil red O staining. Transcriptome sequencing and untargeted metabolomics were performed on rat liver and serum samples, integrated with bioinformatics analyses. Key metabolites(branched-chain amino acids, BCAAs), amino acid transporters, amino acid metabolites, critical enzymes for amino acid metabolism, resistin, adiponectin(ADPN), and mammalian target of rapamycin(mTOR) pathway-related molecules were quantified using quantitative real-time polymerase chain reaction(qRT-PCR), Western blot, and enzyme-linked immunosorbent assay(ELISA). The results showed that compared with the normal group, the model group had significantly increased serum levels of total cholesterol(TC), triglycerides(TG), low-density lipoprotein cholesterol(LDL-C), and resistin and significantly decreased ADPN levels. Hepatocytes in the model group exhibited loose arrangement, significant lipid accumulation, fatty degeneration, and pronounced inflammatory cell infiltration. In liver tissue, the mRNA transcriptional levels of solute carrier family 7 member 2(Slc7a2), solute carrier family 38 member 2(Slc38a2), solute carrier family 38 member 4(Slc38a4), and arginase(ARG) were significantly downregulated, while the mRNA transcriptional levels of solute carrier family 1 member 4(Slc1a4), solute carrier family 16 member 1(Slc16a1), and methionine adenosyltransferase(MAT) were upregulated. Furthermore, the mRNA transcription and protein expression levels of branched-chain α-keto acid dehydrogenase E1α(BCKDHA) and DEP domain-containing mTOR-interacting protein(DEPTOR) were downregulated, while mRNA transcription and protein expression levels of mTOR, as well as ribosomal protein S6 kinase 1(S6K1), were upregulated. The levels of BCAAs and S-adenosyl-L-methionine(SAM) were elevated. The serum level of 6-hydroxymelatonin was significantly reduced, while imidazole-4-one-5-propionic acid and N-(5-phospho-D-ribosyl)anthranilic acid levels were significantly increased. Compared with the model group, Qingrun Decoction significantly reduced blood lipid and resistin levels while increasing ADPN levels. Hepatocytes had improved morphology with reduced inflammatory cells, and fatty degeneration and lipid deposition were alleviated. Differentially expressed genes and differential metabolites were mainly enriched in amino acid metabolic pathways. The expression levels of Slc7a2, Slc38a2, Slc38a4, and ARG in the liver tissue were significantly upregulated, while Slc1a4, Slc16a1, and MAT expression levels were significantly downregulated. BCKDHA and DEPTOR expression levels were upregulated, while mTOR and S6K1 expression levels were downregulated. Additionally, the levels of BCAAs and SAM were significantly decreased. The serum level of 6-hydroxymelatonin was increased, while those of imidazole-4-one-5-propionic acid and N-(5-phospho-D-ribosyl)anthranilic acid were decreased. In summary, Qingrun Decoction may improve amino acid metabolism reprogramming, inhibit mTOR pathway activation, alleviate insulin resistance in the liver, and mitigate pathological damage of liver tissue in T2DM rats by downregulating hepatic BCAAs and SAM and regulating key enzymes involved in amino acid metabolism, such as BCKDHA, ARG, and MAT, as well as amino acid metabolites and transporters.
Animals ; Drugs, Chinese Herbal/administration & dosage* ; Rats ; Insulin Resistance ; Diabetes Mellitus, Type 2/genetics* ; Male ; Liver/drug effects* ; Amino Acids/metabolism* ; Rats, Sprague-Dawley ; Humans ; Metabolic Reprogramming

Paclitaxel (PTX), a valuable natural product derived from Taxus species, exhibits remarkable anti-cancer properties. It penetrates nanopores in microtubule walls, interacting with tubulin on the lumen surface and disrupting microtubule dynamics, thereby inducing cytotoxic effects in cancer cells. PTX and its derivatives have gained approval for treating various diseases due to their low toxicity, high efficiency, and broad-spectrum application. The widespread success and expanding applications of PTX have led to increased demand, raising concerns about accessibility. Consequently, researchers globally have focused on developing alternative production methods and applying nanocarriers in PTX delivery systems to enhance bioavailability. This review examines the challenges and advancements in PTX sourcing, production, physicochemical properties, anti-cancer mechanisms, clinical applications, trials, and chemo-immunotherapy. It aims to provide a comprehensive reference for the rational development and effective utilization of PTX.
Humans ; Paclitaxel/pharmacology* ; Antineoplastic Agents, Phytogenic/pharmacology* ; Neoplasms/drug therapy* ; Animals ; Taxus/chemistry*

Circular RNAs are novel non-coding RNAs with multiple biological functions, which can participate in biological processes such as the occurrence, development, invasion, and metastasis of liver cancer, as well as drug resistance of liver cancer. This article reviews the roles and mechanisms of circR-NAs in chemotherapy resistance, targeted therapy resistance and immunotherapy resistance in liver cancer, in order to provide new ideas for solving liver cancer resistance.

Mongolians have a long history of using prescriptions, which can be classified into four stages as follows: the germination and experience accumulation stage before the 13 th century, the theoretical formation stage from the 13 th to 16 th century, the rapid development stage from the 17 th to 20 th century, and the leaping development stage from the mid-20 th century to the present. The prescriptions from the ancient classical or representative medical books have always been used by Mongolian physicians for generations, and they are still in use due to the definite curative effects. In 2008, the Notice on Issuing the Supplementary Provisions to the Registration and Management of Traditional Chinese Medicine(TCM) described that China has attached more importance to the excavation and development of classical prescriptions. As stipulated in the Law of the People's Republic of China on Traditional Chinese Medicine, the classical prescriptions should be those available in ancient TCM classics and still in wide use, with exact curative effects, distinct features, and obvious advantages. This paper expounded the historical formation and development of classical prescriptions in Mongo-lian medicine, introduced the five most influential ancient medical books revealing the formation and development of these classic prescriptions, and traced the origin of such classical prescriptions as Wenguanmu Siwei Decoction, Shouzhangshen Bawei Decoction, Jianghuang Siwei Decoction and summarized the origin, development history and characteristics of classical prescriptions in Mongolian medicine, aiming to provide a reference for their further research and development.
Books ; China ; Drugs, Chinese Herbal ; Humans ; Medicine, Chinese Traditional ; Medicine, Mongolian Traditional ; Prescriptions

Objective To study the related factors of central lymph node(CLN) metastasis in papillary thyroid carcinoma ( PTC ),the indications and the extent of central neck dissection ( CND ).Methods A total of 153 cases treated between Jan.2009 and Dec.2010 was analysed retrospectively.Of the cases 28 males and 125 cases females,with a mean age of (44 ± 14) years.T1,T2,and T3 diseases accounted for 51,10 and 81 cases,respectively; Ⅰ,Ⅱ,Ⅲ and Ⅳ diseases for 88,3,26 and 36 cases,respectively.Multifocal tumors were found in 63 cases.The related clinicopathologic factors were analyzed,including sex,age,tumor size,extrathyroidal extension,and multifocal tumor.Results All the cases had total/near total thyroidectomy and CND,of them 64 cases had unilateral neck dissection and 18 cases had bilateral neck dissection.CLN metastases existed in 68.6％ ( 105/153 ) cases,37.2％ (57/153) for unilateral and 31.4％ (48/153) for bilateral respectively.The rates of CLN metastasis were 86.6％ (71/82)in cN1 cases and 47.9％ (34/71) cN0 cases,respectively,and the rates of bilateral CLN metastases were 45.1％(37/82) in cN1 cases and 15.5％ (11/71) in cN0 cases. Multivariate analysis showed that extrathyroidal extension( P =0.002,OR =3.502) was an independent risk factor for CLN metastasis and that lateral neck lymph node metastasis( P =0.028,OR =3.080),surrounding tissue invasion ( P =0.014,OR =3.113 ),and maximum tumor diameter greater than 1 cm ( P =0.012,OR =3.732) were independent risk factors for bilateral CLN metastases.Conclusions It is indicated that ipsilateral CND should be obligatory for PTC. Intraoperative frozen section examination should be routine.Bilateral CND should be conducted when ipsilateral CLN metastases accompanied by one of following issues such as more invasive tumor(surrounding tissue invasion,T3 or T4 disease),maximum tumor diameter greater than 1 cm,and lateral neck lymph node metastasis.

OBJECTIVEThis clinical study was designed to evaluate the efficacy and toxicity of the combined regimen of docetaxel, 5-Fu and DDP (TPF) in the treatment of advanced or relapsed nasopharyngeal carcinoma (NPC).

METHODSFifty-six patients with newly diagnosed or recurrent/metastatic NPC following chemotherapy or radiotherapy were enrolled. Both docetaxel and DDP were administered intravenously for 6 hours at the dose of 70 mg/m2 on D1. 5-Fu was given at a dose of 400-500 mg/m2 for 6 hours from D1 to D5. Dexamethasone was routinely administered before injection of docetaxel. This combination was repeated every 3 to 4 weeks, and continued for 4-6 cycles or until PD for the responders.

RESULTSFifty-one (91.1%) patients were evaluable for response assessment. The response rate for whole group was 72.5% (37/51) with a CR rate of 9.8% (5/51). The stable disease accounted for 17.6% (9/51). There were 17(30.4%) chemotherapy-naïve patients. The overall response rate in those was 82.4% with a CR rate of 29.4%. However, the response rate for previously treated patients was 64.7% without CR. Twelve patients had progressed disease, including 5 (8.9%) died of disease progression with a median follow-up of 11 month (ranged from 1 to 19 months). Totally, 196 courses of chemotherapy were administered. The major toxicity was myelosupression, nausea/vomiting. The incidence of leucopenia was 48% with 22.2% of these in NCI grade II or IV. But only 2 patients (3.6%) experienced leucopenia with a fever. Other mild toxicities including alopecia, asthenia, mucositis and diarrhea were also observed.

CONCLUSIONOur preliminary outcome shows docetaxel, 5-Fu and DDP combination is effective and safe for the patients with advanced or relapsed nasopharyngeal carcinoma. But further clinical study is warranted.

Adolescent ; Adult ; Aged ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Carcinoma, Squamous Cell ; drug therapy ; pathology ; Cisplatin ; administration & dosage ; Female ; Fluorouracil ; administration & dosage ; Follow-Up Studies ; Humans ; Leukopenia ; chemically induced ; Male ; Middle Aged ; Nasopharyngeal Neoplasms ; drug therapy ; pathology ; Nausea ; chemically induced ; Neoplasm Recurrence, Local ; Neoplasm Staging ; Remission Induction ; Taxoids ; administration & dosage ; Young Adult

OBJECTIVETo conduct a molecular epidemiological survey on the mitochondrial DNA C1494T mutation in non-syndromic hearing loss patients in Chinese population.

METHODSPolymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) were used to screen the mitochondrial DNA 12S rRNA C1494T mutation in 20 patients with aminoglycoside antibiotic induced hearing loss, 136 sporadic non-syndromic hearing loss patients and 50 probands of pedigrees with non-syndromic hearing loss.

RESULTSThe C1494T mutation did not appear in all cases except for the positive control.

CONCLUSIONIncidence of mitochondrial DNA C1494T mutation is much lower than that of mitochondrial DNA A1555G mutation in non-syndromic hearing loss of Chinese population. Mitochondrial DNA C1494T mutation may be a rare variation in non-syndromic hearing loss and is not the main cause of aminoglycoside antibiotic induced-deafness.

Adolescent ; Aminoglycosides ; adverse effects ; Anti-Bacterial Agents ; adverse effects ; Asian Continental Ancestry Group ; genetics ; Child ; China ; DNA, Mitochondrial ; genetics ; Female ; Hearing Loss ; chemically induced ; ethnology ; genetics ; Humans ; Male ; Point Mutation ; Polymerase Chain Reaction ; Polymorphism, Restriction Fragment Length ; RNA, Ribosomal ; genetics

OBJECTIVETo suppress the expression of CCR5 and CXCR4, the co-receptors for human immunodeficiency virus type 1 ( HIV-1), and thus inhibit HIV-1 from entering cells.

METHODSDNA fragments encoding either CCR5 or CXCR4 were amplified from healthy human peripheral blood mononuclear cells (PBMCs) by reverse transcript polymerase chain reaction (RT-PCR) and sequencing was performed. Correct fragments were inserted into Shuttle plasmid inversely, which was recombined with backbone plasmid containing homologous adenoviral genome in E. coli BJ5183. The recombinant plasmids were transfected into 293 cells in which they were packaged and amplified. Recombinant adenoviruses containing antisense RNA of CCR5 or CXCR4 were obtained and identified by RT-PCR, and the titres of them were determined by cytopathic effect (CPE) method. The U937 and MT4 cells were infected by recombinant adenoviruses containing antisense RNA of CCR5 (multiplicity of infection, MOI = 100) and CXCR4 (MOI = 200), respectively. The expression of co-receptors on infected cell was measured by fluorescence activated cell sorter at 24, 48, 72 hours and 10 days after infection. In addition, the chemotactic activity and proliferation of infected cells were detected with Boyden chamber and 3H incorporation respectively.

RESULTSWe constructed the recombinant plasmids and obtained the recombinant adenoviruses which contained antisense RNA of CCR5 or CXCR4 and were designated as pAd-antiR5 and pAd-antiX4 respectively. The titers of recombinant adenoviruses pAd-antiR5 and pAd-antiX4 were 5 x 10" PFU/ml and 7 x 10(10) PFU/ml, respectively. The expression rate of CCR5 on U937 cells decreased from 82. 10% (blank control) to 1.12% (Ad-antiR5 infected) , and that of CXCR4 on MT4 cells decreased from 42% (blank control) to 1.03% (Ad-antiX4 infected) 24 hours later. The expression rates of CCR5 on Ad-antiR5 infected U937 cells were 1.02% , 1.26% , 1.23% at 48 hours, 72 hours, and 10 days later, respectively. The expression rates of CXCR4 on Ad-antiX4 infected MT4 cells were 1.13%, 1.17%, 1.22% at 48 hours, 72 hours, and 10 days later, respectively. Moreover, the recombinant adenovirus had no effects on chemotactic activity and proliferation of the cells.

CONCLUSIONThe recombinant adenovirus containing antisense CCR5 or CXCR4 can remarkably decrease the expression of co-receptors for HIV-1 on U937 or MT4 cells without affecting their chemotactic activities and proliferative abilities.

Adenoviridae ; genetics ; Cell Line, Transformed ; Cell Proliferation ; Chemotaxis ; Down-Regulation ; Genetic Vectors ; Humans ; RNA, Antisense ; genetics ; RNA, Messenger ; genetics ; Receptors, CCR5 ; biosynthesis ; genetics ; Receptors, CXCR4 ; biosynthesis ; genetics ; Transfection ; U937 Cells