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

Objective: To investigate the clinical features and long-term prognosis of primary biliary cholangitis (PBC) in patients with past hepatitis B virus (HBV) infection. Methods: 353 cases with PBC who visited the Liver Disease Center of Beijing Friendship Hospital Affiliated to Capital Medical University between January 2000 and January 2018 were retrospectively analyzed and were divided into the past HBV infection group (156 cases) and the no HBV infection group (197 cases). The two groups' baseline clinical features were compared. Ursodeoxycholic acid response rate after one year, GLOBE score, UK-PBC score, and long-term liver transplantation-free survival rate were compared through outpatient and telephone follow-up. Results: PBC with past HBV infection had a significantly reduced female proportion compared to the no HBV infection group (91.9% vs. 79.5%, P = 0.001). However, there were no statistically significant differences in age, biochemical indices, immunological indicators, platelet count, cirrhosis proportion, and others. Ursodeoxycholic acid biochemical response rate was reduced in patients with past HBV infection at the end of one year of treatment, but the difference was not statistically significant (65.8% vs. 78.2%, P = 0.068). In addition, there were no statistically significant differences between the GLOBE score (0.57 vs. 0.59, P = 0.26) and UK-PBC 5-year (2.87% vs. 2.87%, P = 0.38), 10-year (9.29% vs. 8.2%, P = 0.39) and 15-year liver transplantation rates (16.6% vs. 14.73%, P = 0.39). Lastly, the overall 5-year liver transplantation-free survival rate had no statistically significant difference between the two groups of patients (86.4% vs. 87.5%, P = 0.796). Conclusion: Primary biliary cholangitis had no discernible effect in terms of age at onset, biochemical indices, immunological indicators, cirrhosis proportion, ursodeoxycholic acid response rate after one year, GLOBE score, UK-PBC score, or overall liver transplantation-free survival rate in patients with past hepatitis B virus infections.

Humans ; Carcinoma, Mucoepidermoid/pathology* ; Breast/pathology*

Objective:To investigate the influence of abnormal blood pressure circadian rhythms and the morning surge on aortic stiffness in elderly patients with isolated systolic hypertension(ISH).Methods:A total of 300 untreated elderly(≥60 years)patients with ISH were enrolled.24-hour ambulatory blood pressure was measured by using a non-invasive portable ambulatory sphygmomanometer with an inflatable cuff.Brachial-ankle pulse wave velocity(baPWV)and the ankle-brachial pressure index(ABI)were measured by using an automated device.Patients were divided into the dipper(n=95), no-dipper(n=177)and extreme dipper(n=28)groups according to the rate of nocturnal blood pressure reduction.They were also divided into the morning surge(n=88)and no morning surge(n=212)groups according to the morning blood pressure surge(MBPS). Differences between the groups were compared.Correlations between the parameters were calculated by partial correlation analyses.The effects on baPWV and ABI were calculated by multiple linear regression analyses.Results:baPWV was higher in the extreme dipper group than in the dipper and no dipper groups[(1 402±234)cm/s vs.(1 467±114)cm/s vs.(1 538±140)cm/s, P<0.01], while ABI values were lower in the extreme dipper group than in the dipper group(0.98±0.10 vs.1.05±0.12, P<0.01)and the no dipper group(0.98±0.10 vs.1.03±0.12, P<0.05). Moreover, baPWV[(1 508±170)cm/s vs.(1 430±163)cm/s, P<0.01]was higher while ABI values(0.98±0.13 vs.1.06±0.11, P<0.01)were lower in the morning surge group than in the no morning surge group.baPWV was positively correlated with daytime Systolic blood pressure(dSBP)( r=0.169, P<0.01), 24 hSBPCV( r=0.143, P<0.05), and MBPS( r=0.157, P<0.01), while ABI was negatively correlated with dSBP( r=-0.146, P=0.011)and MBPS( r=-0.321, P<0.01). Age( P<0.01), dSBP( P<0.05)and 24 h systolic blood pressure variation coefficient( P<0.05)were independent factors for baPWV, while dSBP and MBPS were independent factors for ABI(all P<0.01). Conclusions:Abnormal blood pressure circadian rhythms and the morning surge are associated with increased aortic stiffness in elderly patients with ISH.

BACKGROUND: To observe the effects of Chinese medicine (CM) Polygonum cuspidatum (PC) on adenosine 5'-monophosphate-activated protein kinase (AMPK), forkhead box O3α (FOXO3α), Toll-like receptor-4 (TLR4), NACHT, LRR and PYD domains-containing protein 3 (NLRP3), and monocyte chemoattractant protein-1 (MCP-1) expression in a rat model of uric acid-induced renal damage and to determine the molecular mechanism. METHODS: A rat model of uric acid-induced renal damage was established, and rats were randomly divided into a model group, a positive drug group, and high-, medium-, and low-dose PC groups (n=12 per group). A normal group (n=6) was used as the control. Rats in the normal and model groups were administered distilled water (10 mL•kg) by intragastric infusion. Rats in the positive drug group and the high-, medium-, and low-dose PC groups were administered allopurinol (23.33 mg•kg), and 7.46, 3.73, or 1.87 g•kg•d PC by intragastric infusion, respectively for 6 to 8 weeks. After the intervention, reverse transcription polymerase chain reaction, Western blot, enzyme linked immunosorbent assay, and immunohistochemistry were used to detect AMPK, FOXO3α, TLR4, NLRP3, and MCP-1 mRNA and protein levels in renal tissue or serum. RESULTS: Compared with the normal group, the mRNA transcription levels of AMPK and FOXO3α in the model group were significantly down-regulated, and protein levels of AMPKα1, pAMPKα1 and FOXO3α were significantly down-regulated at the 6th and 8th weeks (P<0.01 or P<0.05). The mRNA transcription and protein levels of TLR4, NLRP3 and MCP-1 were significantly up-regulated (P<0.01 or P<0.05). Compared with the model group, at the 6th week, the mRNA transcription levels of AMPK in the high- and medium-dose groups, and protein expression levels of AMPKα1, pAMPKα1 and FOXO3α in the high-dose PC group, AMPKα1 and pAMPKα1 in the mediumdose PC group, and pAMPKα1 in the low-dose PC group were significantly up-regulated (P<0.01 or P<0.05); the mRNA transcription and protein levels of TLR4 and NLRP3 in the 3 CM groups, and protein expression levels of MCP-1 in the medium- and low-dose PC groups were down-regulated (P<0.01 or P<0.05). At the 8th week, the mRNA transcription levels of AMPK in the high-dose PC group and FOXO3α in the medium-dose PC group, and protein levels of AMPKα1, pAMPKα1 and FOXO3α in the 3 CM groups were significantly up-regulated (P<0.01 or P<0.05); the mRNA transcription levels of TLR4 in the medium- and low-dose PC groups, NLRP3 in the high- and low-dose PC groups and MCP-1 in the medium- and low-dose PC groups, and protein expression levels of TLR4, NLRP3 and MCP-1 in the 3 CM groups were down-regulated (P<0.01 or P<0.05). CONCLUSION PC up-regulated the expression of AMPK and its downstream molecule FOXO3α and inhibited the biological activity of TLR4, NLRP3, and MCP-1, key signal molecules in the immunoinflammatory network pathway, which may be the molecular mechanism of PC to improve hyperuricemia-mediated immunoinflflammatory metabolic renal damage.
AMP-Activated Protein Kinases ; physiology ; Animals ; Chemokine CCL2 ; blood ; Disease Models, Animal ; Fallopia japonica ; Forkhead Box Protein O3 ; physiology ; Hyperuricemia ; complications ; Kidney Diseases ; drug therapy ; etiology ; Male ; Plant Extracts ; pharmacology ; Rats ; Rats, Sprague-Dawley ; Signal Transduction ; drug effects ; Uric Acid

Objective To explore the management methods of medical equipment maintenance. Methods Based on the staffing of hospital engineering technician, the difference between levels of hospitals in medical equipment maintenance management was explored from the aspects of maintenance, preventive maintenance, use training of medical equipment, medical equipment maintenance management system and etc. Results The management methods of medical equipment maintenance were different corresponding to the configurations of the departments of clinical engineering. Conclusion The maintenance management method corresponding to the staffing of hospital engineering technician as well as the correct use of modern medical equipment contribute to insuring the safety and reliability and enhancing the availability and utilization rate.

OBJECTIVETo study the relationship between surface markers of CD56 and CD19 and karyotypes and prognosis in multiple myeloma.

METHODSA total of 126 cases of newly diagnosed multiple myeloma in the first hospital of Peking university from 2011 to 2015 were enrolled in this study. Cytogenetic abnormalities and immunophenotypes were detected by using fluorescence in situ hybridization and flow cytometry respectively before chemotherapy. Bone marrow smear was used for detection of abnormal plasma cell infiltration. By combining with their basic data, the relationship between immunophenotypes, cytogenetics and prognosis of MM was analyzed.

RESULTS(1) The median of myeloma cells in the 126 patients was 0.24（0.01-0.97）; the median of myeloma cells in 116 patients who have immunophenotype datas was 0.25（0.01-0.97）； the median of myeloma cells in CD19 positive patients was 0.11（0.01-0.53）; the median of myeloma cells in CD19 negative patients was 0.26（0.01-0.97）. The median of myeloma cells in CD19 positive patients was much lower than that in CD19 negative patients（P=0.036）. (2)In 116 patients detected by the immunophenotype, the myeloma cells expressed CD19,CD20,CD56 and CD117. Compared with CD56 negative patients(45/116,38.79%),CD56 positive patients(71/116,61.21%) had a clearly favorable disease outcome（OS was 53.0 month vs 31.0 month,P=0.016; PFS was 37.5 months vs 18.4 months, P=0.036）. (3)CD19 positive patients was 16.38%（19/116）,CD19 negative patients was 83.62%（97/116）； CD19 positive MM and CD19 negative MM had no difference in OS and PFS. (4)CD117 positive rate in CD19 positive patients was 42.11%(8/19), the CD117 positive rate in CD19 negative patients was 18.57%(18/97), the CD19 expression positively correlated with CD117 expression. (5)FISH detection was done for 67 newly diagnosed MM patients, 8 patients showed normal karyotypes(11.94%), 59 patients had abnormal karyotypes(88.06%). The most common abnormal karyotypes were IgH rearragement which occurred in 47 patients(70.15%). Other abnormal karyotypes included 1q21+, del(13q14),del(13q14.3),del(17p13) . These abnormal karyotypes occurred in 37 patients（55.22%）,31 patients（46.27%）,33 patients（49.25%） and 13 patients（19.40%） respectively. In comparison with CD19 negative MM patients, the incidence rate of 1q21+ and del(13q14.3) was significantly lower in CD19 positive patients(1q21+:33.33% vs 61.54%,P=0.016; del(13q14.3): 33.33% vs 53.85%,P=0.043）.

CONCLUSIONThe prognosis of CD56 positive MM patients is better than that of CD56 negative MM patients, CD19 negative MM has more abnormal karyotypes and bone marrow infiltration,but they have no statistical prognostic differences.

Objective To evaluate the effect of ditching for drain on the control of the breed of Oncomelania hupensis snails in beaches of Dongting Lake. Methods From November,2009 to November,2012,an O. hupensis snail infested beach of the Yueyang jail and an O. hupensis snail infested beach of Junshan District were selected as research fields in the eastern Dongting Lake area,and the former,as the intervention field,was performed with the ditching for drain by excavators and the latter,as the control field,was not. Results Before the project implemented,the average soil moisture contents on the beaches in dry seasons of the two fields were both about 35.56%. After the project implemented,in the intervention field,the average soil mois?ture content was 26.53%which was significantly lower than that(35.56%)in the control field(F=6.53,P<0.05). The under?ground water levels in different heights in the intervention field were lower than those in the control field (χ2 = 33.33,P <0.05). Before the project implemented,the natural death rates of the snails were 0.98%and 0.89%in the two research fields re?spectively(P>0.05),and after the project implemented(in 2012),no adult and young snails were found in the interventional field,but in the control field,the average densities of living snails and young snails were 29.37 snails/0.1 m2 and 213±108.45 snails/0.1 m2 respectively. Conclusion The intervention of ditching for drain can decrease the soil moisture contents quickly and change the ecological condition,therefore,can control the breed of O. hupensis snails in the beaches of Dongting Lake.

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.

[Objective]To investigate the efficacy and cost analysis ofmicrosurgical clipping and vascular embolization in the treatment of patients with cerebral aneurysms.[Methods]Two hundred and fitly-one patients with cerebral ameurysms,admitted to our hospital from January 2007 to December 2010,were collected in our study;170 patients (174 aneurysms) received microsurgical surgical clipping (clipping group) and other 181 patients (185 aneurysms) were performed vascular embolization (embolization group).Duration of hospitalization,vascular occlusion rate,intraoperative rupture rate,hospital mortality and happening of complications were compared between the 2 groups;and the efficacy were evaluated by modified Rankin scale (mRS) and cost analysis of the 2 treatments were compared 3 months after the surgeries.[Results] The length of hospital stays and cerebral aneurysm rupture rate in patients of the embolization group were significantly shorter/lower than those in the clipping group (P＜ 0.05);the scores of mRS showed no significant differences between the 2 groups (P＞0.05).The cost and sensitivity analysis indicated that the ratio of average cost/good prognosis rate in the clipping group was smaller as compared with that in the embolization group.[Conclusion] The efficacies of microsurgical clipping and embolization in the treatment of cerebral aneurysms are considerable,and both of them have their advantages and disadvantages respectively;however,the microsurgical clipping is cost-effective and economical.