Shexiang Tongxin Dropping Pill Promotes Angiogenesis through VEGF/eNOS Signaling Pathway on Diabetic Coronary Microcirculation Dysfunction.

OBJECTIVE: To study the effect of Shexiang Tongxin Dropping Pill (STDP) on angiogenesis in diabetic cardiomyopathy mice with coronary microcirculation dysfunction (CMD). METHODS: According to a random number table, 6 of 36 SPF male C57BL/6 mice were randomly selected as the control group, and the remaining 30 mice were injected with streptozotocin intraperitoneally to replicate the type 1 diabetes model. Mice successfully copied the diabetes model were randomly divided into the model group, STDP low-dose group [15 mg/(kg·d)], medium-dose group [30 mg/(kg·d)], high-dose group [60 mg/(kg·d)], and nicorandil group [15 mg/(kg·d)], 6 in each group. The drug was given by continuous gavage for 12 weeks. The cardiac function of mice in each group was detected at the end of the experiment, and coronary flow reserve (CFR) was detected by chest Doppler technique. Pathological changes of myocardium were observed by hematoxylin-eosin staining, collagen fiber deposition was detected by masson staining, the number of myocardial capillaries was detected by platelet endothelial cell adhesion molecule-1 staining, and the degree of myocardial hypertrophy was detected by wheat germ agglutinin staining. The expression of the vascular endothlial growth factor (VEGF)/endothelial nitric oxide synthase (eNOS) signaling pathway-related proteins in myocardial tissue was detected by Western blot. RESULTS: Compared with the model group, medium- and high-dose STDP significantly increased the left ventricular ejection fraction and left ventricular fraction shortening (P<0.01), obviously repaired the disordered cardiac muscle structure, reduced myocardial fibrosis, reduced myocardial cell area, increased capillary density, and increased CFR level (all P<0.01). Western blot showed that high-dose STDP could significantly increase the expression of VEGF and promote the phosphorylation of vascular endothelial growth factor receptor 2, phosphoinositide 3-kinase, protein kinase B, and eNOS (P<0.05 or P<0.01). CONCLUSION: STDP has a definite therapeutic effect on diabetic CMD, and its mechanism may be related to promoting angiogenesis through the VEGF/eNOS signaling pathway.

Diagnostic value of serum human epididymis protein 4, carbohydrate antigen 125 and their combination in endometrial cancer: A meta-analysis.

BACKGROUND: To systematically analyze the value of human epididymis protein 4 (HE4) and carbohydrate antigen 125 (CA125) in the diagnosis of endometrial cancer, so as to provide evidence-based medical evidence for the selection of serum tumor markers in the early screening of endometrial cancer. METHODS: We comprehensively searched relevant literature in the Cochrane Library, EMBASE, PubMed, Web of Science, CNKI, VIP, WanFang, and CBM from the date of establishment to November 31, 2021. Quality assessment of diagnostic accuracy studies 2 was applied to evaluate the quality of the included literature. We used Stata 16.0 to calculate the pooled sensitivity (SEN), specificity (SPE), positive likelihood ratio (PLR), negative likelihood ratio (NLR) and diagnostic odds ratio (DOR) and plot summary receiver operating characteristic curve, as well as to assess diagnostic accuracy using the area under the curve (AUC). RESULTS: A total of 25 studies, including 1980 patients and 2345 controls, were included in this meta-analysis. The pooled SEN, SPE, PLR, NLR, DOR, and AUC of HE4 were 0.58 (95% CI 0.52-0.63), 0.95 (95% CI 0.92-0.97), 11.57 (95% CI 6.88-19.48), 0.45 (95% CI 0.39-0.51), 25.92 (95% CI 14.84-45.26), and 0.80 (95% CI 0.76-0.83), respectively. The pooled SEN, SPE, PLR, NLR, DOR, and AUC of CA125 were 0.41 (95% CI 0.34-0.49), 0.91 (95% CI 0.85-0.95), 4.55 (95% CI 2.73-7.58), 0.65 (95% CI 0.57-0.74), 7.03 (95% CI 3.92-12.62), and 0.68 (95% CI 0.64-0.72), respectively. The pooled SEN, SPE, PLR, NLR, DOR, and AUC of HE4 + CA125 were 0.67 (95% CI 0.60-0.73), 0.92 (95% CI 0.87-0.95), 8.59 (95% CI 5.32-13.86), 0.36 (95% CI 0.30-0.44), 23.80 (95% CI 13.86-40.86), and 0.85 (95% CI 0.82-0.88), respectively. CONCLUSION: This Meta-analysis found that HE4 alone or in combination with CA125 showed better diagnostic efficacy than CA125, regardless of clinical stage and pathological type. HE4 + CA125 had slightly higher diagnostic efficiency than HE4, but did not show significant advantages. While the studies were heterogeneous, the credibility of the findings needs to be further confirmed by more homogeneous, prospective, and large sample size studies.

Growth differentiation factor 15 predicts cardiovascular events in stable coronary artery disease.

BACKGROUND: Growth differentiation factor 15 (GDF-15) has been explored as a potential biomarker for various inflammatory diseases and cardiovascular events. This study aimed to assess the predictive role of GDF-15 levels in cardiovascular events and all-cause mortality, considering traditional risk factors and other biomarkers. METHODS: A prospective study was conducted and 3699 patients with stable coronary artery disease (CAD) were enrolled into the research. Baseline GDF-15 levels were measured. Median follow-up was 3.1 years during the study. We analyzed clinical variables and several biomarkers. Multivariable Cox regression analysis was performed to evaluate prognostic performance of GDF-15 levels in predicting myocardial infarction (MI), heart failure, stroke, cardiovascular death, and non-cardiovascular death. RESULTS: Baseline GDF-15 levels for 3699 patients were grouped by quartile (≤ 1153, 1153-1888, 1888-3043, > 3043 ng/L). Higher GDF-15 levels were associated with older age, male gender, history of hypertension, and elevated levels of N-terminal pro B-type natriuretic peptide (NT-pro BNP), soluble suppression of tumorigenesis-2 (sST2), and creatine (each with P < 0.001). Adjusting for established risk factors and biomarkers in Cox proportional hazards models, a 1 standard deviation (SD) increase in GDF-15 was associated with elevated risk of clinical events [hazard ratio (HR) = 2.18, 95% confidence interval (CI): (1.52-3.11)], including: MI [HR = 2.83 95% CI: (1.03-7.74)], heart failure [HR = 2.71 95% CI: (1.18-6.23)], cardiovascular and non-cardiovascular death [HR = 2.48, 95% CI (1.49-4.11)] during the median follow up of 3.1 years. CONCLUSIONS: Higher levels of GDF-15 consistently provides prognostic information for cardiovascular events and all cause death, independent of clinical risk factors and other biomarkers. GDF-15 could be considered as a valuable addition to future risk prediction model in secondary prevention for predicting clinical events in patient with stable CAD.

Effect of exogenous hydrogen sulfide in the nucleus tractus solitarius on gastric motility in rats.

BACKGROUND: Hydrogen sulfide (H2S) is a recently discovered gaseous neurotransmitter in the nervous and gastrointestinal systems. It exerts its effects through multiple signaling pathways, impacting various physiological activities. The nucleus tractus solitarius (NTS), a vital nucleus involved in visceral sensation, was investigated in this study to understand the role of H2S in regulating gastric function in rats. AIM: To examine whether H2S affects the nuclear factor kappa-B (NF-κB) and transient receptor potential vanilloid 1 pathways and the neurokinin 1 (NK1) receptor in the NTS. METHODS: Immunohistochemical and fluorescent double-labeling techniques were employed to identify cystathionine beta-synthase (CBS) and c-Fos co-expressed positive neurons in the NTS during rat stress. Gastric motility curves were recorded by inserting a pressure-sensing balloon into the pylorus through the stomach fundus. Changes in gastric motility were observed before and after injecting different doses of NaHS (4 nmol and 8 nmol), physiological saline, Capsazepine (4 nmol) + NaHS (4 nmol), pyrrolidine dithiocarbamate (PDTC, 4 nmol) + NaHS (4 nmol), and L703606 (4 nmol) + NaHS (4 nmol). RESULTS: We identified a significant increase in the co-expression of c-Fos and CBS positive neurons in the NTS after 1 h and 3 h of restraint water-immersion stress compared to the expressions observed in the control group. Intra-NTS injection of NaHS at different doses significantly inhibited gastric motility in rats (P < 0.01). However, injection of saline, first injection NF-κB inhibitor PDTC or transient receptor potential vanilloid 1 (TRPV1) antagonist Capsazepine or NK1 receptor blockers L703606 and then injection NaHS did not produce significant changes (P > 0.05). CONCLUSION: NTS contains neurons co-expressing CBS and c-Fos, and the injection of NaHS into the NTS can suppress gastric motility in rats. This effect may be mediated by activating TRPV1 and NK1 receptors via the NF-κB channel.

A rare case report of primary uterine and vaginal lymphoma in the elderly.

Uterine lymphoma is rare and usually occurs in middle-aged women. The clinical symptoms lack any specific characteristics. Imaging characteristics usually include uterine enlargement with density and uniform signal soft tissue masses. Magnetic resonance T2 weighted imaging, enhanced scanning, diffusion weighted imaging and apparent diffusion coefficient values have certain characteristics. The gold standard for diagnosis remains a pathological examination of a biopsy specimen. The special feature of this current case was that the uterine lymphoma occurred in an 83-year-old female patient that presented with a pelvic mass for more than 1 month. Based on the imaging findings, a primary uterine lymphoma was considered, but her advanced age of onset did not match the disease. After pathological confirmation, the patient was diagnosed with uterine lymphoma and she received eight cycles of R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisolone) plus local radiotherapy for the large masses. The patients achieved good results. Follow-up enhanced computed tomography imaging showed that the uterine volume had significantly reduced compared with before treatment. The diagnosis of elderly patients with uterine lymphoma can provide a more accurate plan for subsequent treatment.

[Preliminary Application of Contrast-Enhanced Ultrasound in the Treatment of Diabetic Ulcers].

Objective: To investigate the role of contrast-enhanced ultrasound (CEUS) in the treatment of diabetic ulcers. Methods: The clinical data of 27 diabetic patients, who underwent CEUS examination of their ulcers in our hospital between April 2021 and July 2022 were collected. Among them, 26 patients suffered from diabetic foot ulcers, 5 of whom underwent amputation during hospitalization, and one patient suffered from hip ulcer. The 27 patients' mean age was (64.08±12.57) years. Fasting blood glucose levels of the patients were 3.36-34.61 mmol/L, with a mean of (10.62±8.77) mmol/L. Their glycosylated hemoglobin levels were 5.80%-10.70%, with an average of 7.96%±1.50%. Philips EPIQ7 ultrasound system with L9-3 linear probe of 3-9 MHz was used. First, the patients' ulcers were examined with conventional ultrasound to observe for abnormal echo. Then, 2.4 mL SonoVue (Bracco, Italy), a contrast agent, was injected intravenously through the elbow to look for effusion/pus, sinus tract, or dead space in the lesion area, and images were acquired. Results: Among the 27 patients, except for 5 with amputation stumps, 22 patients had wound areas ranging from 0.16 cm 2 to 215 cm 2, all being accompanied by sinus tract formation. Ten patients underwent ultrasound examination during their treatment. The positive rate of the results of conventional ultrasound was 50% (5/10) for identifying effusion/pus and pseudoaneurysm in the deep area of ulcers, while the positive rate of CEUS results was 100% (10/10). In addition to the lesions found by conventional ultrasound, CEUS also found large sinus tracts or dead spaces in the deep surface of ulcers in 5 additional patients. Of the 27 patients, 17 underwent ultrasound examination of the healing status of sinus tracts and dead spaces in the deep areas of ulcers before discharge. No sinus tracts in the deep areas of the ulcers were found by conventional ultrasound. However, relatively small dead spaces or sinus tracts in the deep areas of the ulcers were found in 10 patients by CEUS. Conventional ultrasound and CEUS found that 1 patient had a small amount of fluid in the amputation stump. In the remaining 6 patients, no deep sinus tracts in the ulcers were found by either conventional ultrasound or CUES, and the ulcers healed completely. Conclusion: By examining microvascular perfusion in diabetic wounds with CEUS, we can observe the extent of sinus tracts during treatment and whether the sinus tracts have healed or whether there are still dead spaces before patient discharge, which provides support for clinical decision-making concerning the treatment of diabetic ulcers.

YF343, A Novel Histone Deacetylase Inhibitor, Combined with CQ to Inhibit- Autophagy, Contributes to Increased Apoptosis in Triple- Negative Breast Cancer.

BACKGROUND: Compounds that target tumor epigenetic events are likely to constitute a prominent strategy for anticancer treatment. Histone deacetylase inhibitors (HDACis) have been developed as prospective candidates in anticancer drug development, and currently, many of them are under clinical investigation. We assessed the anticancer efficacy of a now hydroxamate-based HDACi, YF-343, in triple-negative breast cancer development and studied its potential mechanisms. METHODS: YF-343 was estimated as a novel HDACi by the HDACi drug screening kit. The biological effects of YF-343 in a panel of breast cancer cell lines were analyzed by Western blot and flow cytometry. YF-343 exhibited notable cytotoxicity, promoted apoptosis, and induced cell cycle arrest. Furthermore, it also induced autophagy, which plays a pro-survival role in breast cancer cells. RESULTS: The combination of YF-343 with an autophagy inhibitor chloroquine (CQ) significantly suppressed breast tumor progression as compared to the YF-343 treatment alone both in vitro and in vivo. Mechanistically, the molecular mechanism of YF-343 on autophagy was elucidated by gene chip expression profiles, qPCR analysis, luciferase reporter gene assay, chromatin immunoprecipitation assays, immunohistochemical analysis, and other methods. E2F7, a transcription factor, promoted the expression of ATG2A via binding to the ATG2A promoter region and then induced autophagy in triple-negative breast cancer cells treated with YF-343. CONCLUSION: Our studies have illustrated the mechanisms for potential action of YF-343 on tumor growth in breast cancer models with pro-survival autophagy. The combination therapy of YF-343 and CQ maybe a promising strategy for breast cancer therapy.

Arbuscular mycorrhiza mitigates zinc stress on Eucalyptus grandis through regulating metal tolerance protein gene expression and ionome uptake.

Arbuscular mycorrhizal (AM) fungi are symbionts of most terrestrial plants and enhance their adaptability in metal-contaminated soils. In this study, mycorrhized and non-mycorrhized Eucalyptus grandis were grown under different Zn treatments. After 6 weeks of treatment, the growing status and ionome content of plants as well as the expression patterns of metal tolerance proteins and auxin biosynthesis-related genes were measured. In this study, mycorrhized E. grandis showed higher biomass and height at a high level of Zn compared with non-mycorrhized plants. In addition, AM plants accumulated P, Mg, and Mn in roots and P, Fe, and Cu in shoots, which indicate that AM fungi facilitate the uptake of ionome nutrients to promote plant growth. In addition, mycorrhiza upregulated the expression of EgMTP1 and EgMTP7, whose encoding proteins were predicted to be located at the vacuolar membrane. Meanwhile, Golgi membrane transporter EgMTP5 was also induced in AM shoot. Our results suggest that AM likely mitigates Zn toxicity through sequestrating excess Zn into vacuolar and Golgi. Furthermore, the expression of auxin biosynthesis-related genes was facilitated by AM, and this is probably another approach for Zn tolerance.

The complete chloroplast genome of ornamental and medicinal Callerya dielsiana (Fabaceae).

Callerya dielsiana is a Chinese endemic tropical/subtropical liana. We sequenced the complete chloroplast genome with the Illumina Hiseq X-Ten platform. The genome is obtained with 132,301 bp in length, lacking an inverted repeat (IR) region, contains 4 rRNAs, 30 tRNAs genes, and 76 protein-coding genes. The overall GC content is 33.9%. Based on the whole chloroplast genomes of 14 legume species, a phylogenetic tree is constructed and indicated that C. dielsiana belongs to the well-supported tribe Wisterieae. The tribe is sister to Glycyrrhiza and nested within the IRLC (Inverted Repeat-Lacking Clade) group of the subfamily Papilionoideae (Fabaceae).

Prognostic values of human epididymis protein 4 expression in patients with endometrial cancer: A systematic review and meta-analysis.

BACKGROUND: There is no consensus on the correlation between human epididymis protein 4 (HE4) and prognosis of endometrial cancer (EC). Therefore, we performed a meta-analysis to assess the relationship between HE4 and prognosis of EC. METHODS: In this systematic review and meta-analysis, the databases were searched. Correlation of serum or tissue HE4 with clinicopathological characteristics was determined by odds ratio (OR) or standardized mean difference (SMD) with 95% confidence interval (CI), respectively. The hazard ratio (HR) with 95% CI was calculated to evaluate the correlation between HE4 and survival outcome. RESULTS: A total of 38 published studies were eligible. We found that high levels of serum HE4 were associated with FIGO III-IV stage (SMD = 1.58, 95%CI: 1.18-1.98, p < 0.001), grade 3 (SMD = 0.66, 95%CI: 0.39-0.93, p = 0.001), ≥50% myometrial invasion (SMD = 0.78, 95%CI: 0.58-0.99, p < 0.001), lymphovascular space invasion (SMD = 0.82, 95%CI: 0.54-1.11, p = 0.001), lymph node metastasis (SMD = 1.27, 95%CI: 0.84-1.69, p < 0.001), cervical involvement (SMD = 0.71, 95%CI: 0.43-0.98, p = 0.003), parametrial involvement (SMD = 1.03, 95%CI: 0.71-1.35, p < 0.001) and peritoneal cytology (SMD = 0.49, 95%CI: 0.22-0.75, p < 0.001). High expression of tissue HE4 was only significantly associated with lymph node metastasis (OR = 6.19, 95%CI: 2.07-18.50, p = 0.001). High levels of serum HE4 were significantly associated with poor overall survival (univariate: HR = 3.77, 95%CI: 1.94-7.32, p < 0.001; multivariate: HR = 2.15, 95%CI: 1.65-2.80, p < 0.001) and disease-free survival (univariate: HR = 2.89, 95%CI: 2.14-3.88, p < 0.001; multivariate: HR = 2.31, 95%CI:1.20-2.67, p < 0.001) in EC. Compared with cancer antigen 125, serum HE4 may be a better prognostic indicator for EC. CONCLUSIONS: High HE4 expression is associated with poor prognosis of EC and may be a potential prognostic biomarker for EC.

Proposal to recognise the tribes Adinobotryeae and Glycyrrhizeae (Leguminosae subfamily Papilionoideae) based on chloroplast phylogenomic evidence.

Within the legume family, the taxonomic status of subtribe Glycyrrhizinae of tribe Galegeae and of the genus Adinobotrys has been re-assessed. Based on genome skimming data, we conducted phylogenomic analyses of the inverted repeat-lacking clade within subfamily Papilionoideae. The results support the sister relationship between Glycyrrhizeae and Adinobotrys. Glycyrrhizeae is resurrected based on Glycyrrhiza and Glycyrrhizopsis, and a new tribe, Adinobotryeae, is proposed to accommodate Adinobotrys.

Phylogenomic framework of the IRLC legumes (Leguminosae subfamily Papilionoideae) and intercontinental biogeography of tribe Wisterieae.

The inverted repeat-lacking clade (IRLC) is one of the most derived clades within the subfamily Papilionoideae of the legume family, and includes various economically important plants, e.g., chickpeas, peas, liquorice, and the largest genus of angiosperms, Astragalus. Tribe Wisterieae is one of the earliest diverged groups of the IRLC, and its generic delimitation and spatiotemporal diversification needs further clarifications. Based on genome skimming data, we herein reconstruct the phylogenomic framework of the IRLC, and infer the inter-generic relationships and historical biogeography of Wisterieae. We redefine tribe Caraganeae to contain Caragana only, and tribe Astragaleae is reduced to the Erophaca-Astragalean clade. The chloroplast capture scenario was hypothesized as the most plausible explanation of the topological incongruences between the chloroplast CDSs and nuclear ribosomal DNA trees in both the Glycyrrhizinae-Adinobotrys-Wisterieae clade and the Chesneyeae-Caraganeae-Hedysareae clade. A new name, Caragana lidou L. Duan & Z.Y. Chang, is proposed within Caraganeae. Thirteen genera are herein supported within Wisterieae, including a new genus, Villosocallerya L. Duan, J. Compton & Schrire, segregated from Callerya. Our biogeographic analyses suggest that Wisterieae originated in the late Eocene and its most recent common ancestor (MRCA) was distributed in continental southeastern Asia. Lineages of Wisterieae remained in the ancestral area from the early Oligocene to the early Miocene. By the middle Miocene, Whitfordiodendron and the MRCA of Callerya-Kanburia-Villosocallerya Clade became disjunct between the Sunda area and continental southeastern Asia, respectively; the MRCA of Wisteria migrated to North America via the Bering land bridge. The ancestor of Austrocallerya and Padbruggea migrated to the Wallacea-Oceania area, which split in the early Pliocene. In the Pleistocene, Wisteria brachybotrys, W. floribunda and Wisteriopsis japonica reached Japan, and Callerya cinerea dispersed to South Asia. This study provides a solid phylogenomic for further evolutionary/biogeographic/systematic investigations on the ecologically diverse and economically important IRLC legumes.

11-Methoxytabersonine Induces Necroptosis with Autophagy through AMPK/mTOR and JNK Pathways in Human Lung Cancer Cells.

Aspidosperma alkaloids, a subclass of monoterpenoid indole alkaloids rich in the Apocynaceae plants, possess remarkable antitumor activities, but the underlying mechanisms have rarely been reported. In the current project, 11-methoxytabersonine (11-MT), an aspidosperma-type alkaloid isolated from Tabernaemontana bovina, significantly inhibited the viability of two human lung cancer cell lines A549 and H157, and the molecular mechanisms were thus investigated. The results showed that 11-MT killed lung cancer cells via induction of necroptosis in an apoptosis-independent manner. In addition, 11-MT strongly induced autophagy in the two cell lines, which played a protective role against 11-MT-induced necroptosis. Finally, the autophagy caused by 11-MT was found to be via activation of the AMP activated protein kinase (AMPK)/mammalian target of rapamycin (mTOR) and the c-Jun N-terminal kinase (JNK) signaling pathways in both cells. Taken together, 11-MT exhibited an antitumor mechanism different from that of previously reported analogues and could have the potential to serve as a lead compound for the development of new chemotherapy for lung cancer.

Long noncoding RNA LINC01234 silencing exerts an anti-oncogenic effect in esophageal cancer cells through microRNA-193a-5p-mediated CCNE1 downregulation.

BACKGROUND: Long non-coding RNAs (lncRNAs) are transcribed pervasively in the genome and act to regulate chromatin remodeling and gene expression. Dysregulated lncRNA expression has been reported in many cancers, but the role of lncRNAs in esophageal cancer (EC) has so far remained poorly understood. In this study, we aimed to understand the effect of lncRNA LINC01234 on EC development through competitively binding to microRNA-193a-5p (miR-193a-5p). METHODS: The Gene Expression Omnibus (GEO) database was used for microarray-based EC expression profiling. Gain- and loss-of-function analyses were carried out in human EC-derived Eca-109 and EC9706 cells. Expression analyses of miR-193a-5p, LINC01234, CCNE1, caspase-3, p21, Bax, cyclinD1 and Bcl-2 were performed using RT-qPCR and Western blotting. Cell proliferation, colony formation and apoptosis analyses were carried out using MTT, Hoechst 33258 and flow cytometry assays. A xenograft EC model in nude mice was used to evaluate in vivo tumor growth and CCNE1 expression. RESULTS: Microarray-based analyses revealed that LINC01234 expression was increased in primary EC samples, whereas that of miR-193a-5p was decreased. We found that CCNE1 was a target of miR-193a-5p and that LINC01234, in turn, sponges miR-193a-5p. After treatment with si-LINC01234 or miR-193a-5p mimic, EC cells (Eca-109 and EC9706) exhibited cyclinD1 and Bcl-2 downregulation, and caspase-3, p21, Bax and cleaved caspase-3 upregulation. LINC01234 silencing or miR-193a-5p upregulation resulted in decreased proliferation and colony formation, and increased apoptosis of EC cells. In addition, LINC01234 silencing or miR-193a-5p upregulation resulted in reduced in vivo EC tumor growth and CCNE1 expression in nude mice. CONCLUSIONS: We found that silencing of LINC01234 suppresses EC development by inhibiting CCNE1 through competitively binding to miR-193a-5p, which suggests that LINC01234 may represent a novel target for EC therapy.

[Quality Assessment of Euglycemic Glucose Clamp Test].

OBJECTIVE: To explorethe quality of euglycemic glucose clamptest performed in the West China Hospital from 2014 to 2017 and to evaluate whether the quality control indexes are suitable for the quality assessment of the clamp test. METHODS: The data collected from 80 euglycemic glucose clamp tests performed between 2014 and2017 were divided into 4 groups according to the coefficient of variation of the blood glucose concentrations (CVBG): group A (CVBG≤4.5%), group B (4.5% < CVBG≤5.0%), group C (5.0% < CVBG≤5.5%) and group D(CVBG > 5.5%).The differences in percentage of glucose excursion from target range (GEFTR), the duration of GEFTR, the area under curve (AUC) of GEFTR, the mean value of excursion from target glucose (GEFT) and the AUC of GEFT were calculated and compared. RESULTS: In group A, the mean value of CVBG was 3.75%. In group B, the mean value of CVBG was 4.76%. In group C, the mean value of CVBG was 5.28%. The median value of CVBG in group D was 6.07%. The percentage of GEFTR, the duration of GEFTR, the AUC of GEFTR, the mean value of GEFT and the AUC of GEFT in group A were all less than those of other groups (P < 0.05).For the same indexes, there were no significant differences between group B and C, while they were higher in group D compared with the other three groups. CVBG was positively correlated with other quality control indexes (correlation coefficient r was 0.770-0.805). Based on the cut-off point 5% of CVBG, the cut-off points of the percentage of GEFTR, the duration of GEFTR, the AUC of GEFTR, the mean value of GEFT and the AUC of GEFT were 5.8%, 14.6 min, 22.82 mg/dL×min, 3.23 mg/dL, 216.25 mg/dL×min/h respectively, with the sensitivity range from 79.3% to 100% and the specificity range from 74.5% to 89.7%.Combined with these indexes, 8.11% of euglycemic clamps were found to havepoor quality in group A, while 66.67% of euglycemic clamps showed acceptable quality in group C. CONCLUSIONS: The investigators should provide an estimation of the quality of the clamps when reporting the results of the insulin analogues' PK/PD characteristics using euglycemic clamps. CVBG less than 4.5% indicates a good quality, and the above-mentioned quality control indexes especially the AUC of GEFT(cut-off point: 216.25 mg·/dL×min/h) should be evaluated when CVBG is more than 4.5%.False high quality and false low quality euglycemic clamps will be detected and a more precise estimation of quality assessment should be made by the combination of these indexes.

[Current status of blood pressure control in patients with coronary heart disease].

OBJECTIVE: To evaluate the level of blood pressure control in patients with coronary heart disease (CHD) of China in order to provide guidance for the prevention and treatment of CHD. METHODS: The patients with CHD were retrospectively collected from 2011~2014 in PLA General Hospital and Hainan Branch Hospital. Then analyzed the difference of blood pressure compliance rate between different surgical methods percutaneous coronary intervention (PCI), coronary artery bypass grafting(CABG), secondary preventive drugs(aspirin, clopidogrel, nitrates, trimetazidine, nicorandil, hypotensor, hypoglycemic, lipid-lowering drugs) and lifestyle(smoking, drinking, exercise). RESULTS: ①Effects of surgical methods on blood pressure:Male's systolic blood pressure (SBP) and diastolic blood pressure(DBP) in the CABG group were lower in the PCI group and control group, and female's DBP in the CABG group were lower in the PCI group. ②Usage rate of secondary prevention drugs:usage rate of trimetazidine, calcium antagonist, ß-blockers, angiotensin-converting enzyme inhibitor (ACEI) and angiotensin receptor antagonist (ARB) in hypertension group were higher than in normal blood pressure group. ③ Lifestyle condition:compliance rate of blood pressure in the smoking group was lower than that in the non smoking group. And there was no significant difference in blood pressure compliance rate among whether drinking and doing exercise or not. CONCLUSIONS: Blood pressure control in patients with CHD was still not satisfied. Compared with PCI, CABG may be more beneficial in the control of blood pressure in patients with CHD. Smoking cessation and improving the usage rate of secondary preventive drugs are still the main means of blood pressure control.

Early diagnosis of acute kidney injury in aged patients undergoing percutaneous coronary intervention.

In aged patients, acute kidney injury (AKI) is a common clinical complication after percutaneous coronary intervention (PCI), highlighting the need for timely and certain diagnosis of this disease. A single centre, nested case-control study was conducted, which assessed the usefulness of urinary liver-type fatty acid-binding protein (uL-FABP), neutrophil gelatinase-associated lipocalin (uNGAL), and kidney injury molecule-1 (uKIM-1) for early detection of AKI. One hundred and thirty-two patients at or over 60 years old undergoing PCI were included. Serum creatinine (SCr) was measured before PCI, 24 and 48 h after PCI; uL-FABP, uNGAL, and uKIM-1 were measured before PCI, 6, 24, and 48 h after PCI. We identified 16 AKI patients and selected 32 control patients matched by admission time (<1 week), age (±5 years), and gender. In the receiver operating characteristic (ROC) curve analysis, the areas under the curve (AUCs) for the relative measurements of uL-FABP, uNGAL, and uKIM-1 were 0.809, 0.867, and 0.512 at 6 h after PCI, and 0.888, 0.840, and 0.676 at 24 h after PCI, respectively. AUC for the combination of uL-FABP and uNGAL was 0.899 at 6 h after PCI, and 0.917 at 24 h after PCI. Thus, measurement of uL-FABP and uNGAL levels at 6 and 24 h after PCI may be useful in detecting AKI in aged patients. Measurement of uKIM-1 levels provides inferior predictive power for early diagnosis of AKI.

[Pancreatic ß-cell Dysfunction and Apoptosis Induced by Elevated Free Fatty Acids Synergize with Hyperglycemia].

OBJECTIVES: To analysis the effects of glucoxicity and lipotoxicity on the function and apoptosis of pancreatic ß-cells. METHODS: The levels of circulating glucose and free fat acids (FFAs) were elevated by infusion dextrose and fat emulsion in high-fat obese rats. The insulin resistance model obese rats were divided into four gourp: obese group with saline infusion (OB-NS group, n=7), obese group with glucose infusion (OB-GS group, n=9), obese group with Lipid emulsion infusion (OB-FFA group, n=8), obese group with glucose and lipid emulsion infusion (OB-FG group, n=9). Five rats fed with general diet were taken as normal group (NC group).Plasma FFAs and ß-hydroxybutyric acid (ß-HBA) concentrations were determined by an enzymatic colorimetric method. An intravenous glucose tolerance test (IVGTT) was performed to examine the glucose-stimulated insulin secretion in vivo and immunohistochemical staining to detect the storage volume of insulin. FFA and ß-HBA concentrations were measured at baseline and post-infusion. The apoptosis of pancreatic ß-cell was detected byin situ end labeling technique (TUNEL). RESULTS: Glucose infusion rate (GIR) of obese rats was significantly lower than that in NC group [(10.82±1.8) mg/(kg·min) vs. (25.21±1.7) mg/(kg·min), P<0.05], confirming insulin resistance rat model successfully established. The insulin secretion peak load time of OB-FG group rats delayed, and the serum insulin level was significantly lower than that of NC group and OB-NS group during IVGTT. The differences were statistically significant ( P<0.05). Compared with OB-NS and NC groups, storage volume of insulin of OB-GS group reduced, and ß cell apoptosis rate elevated significantly. CONCLUSIONS: Glucolipotoxicity could induce ketone overproduction, insulin resistance and defective insulin secretion.

Novel biomarkers for cardiovascular risk prediction.

Cardiovascular disease (CVD) is the leading cause of death and disability worldwide. The primary prevention of CVD is dependent upon the ability to identify high-risk individuals long before the development of overt events. This highlights the need for accurate risk stratification. An increasing number of novel biomarkers have been identified to predict cardiovascular events. Biomarkers play a critical role in the definition, prognostication, and decision-making regarding the management of cardiovascular events. This review focuses on a variety of promising biomarkers that provide diagnostic and prognostic information. The myocardial tissue-specific biomarker cardiac troponin, high-sensitivity assays for cardiac troponin, and heart-type fatty acid binding proteinall help diagnose myocardial infarction (MI) in the early hours following symptoms. Inflammatory markers such as growth differentiation factor-15, high-sensitivity C-reactive protein, fibrinogen, and uric acid predict MI and death. Pregnancy-associated plasma protein A, myeloperoxidase, and matrix metalloproteinases predict the risk of acute coronary syndrome. Lipoprotein-associated phospholipase A2 and secretory phospholipase A2 predict incident and recurrent cardiovascular events. Finally, elevated natriuretic peptides, ST2, endothelin-1, mid-regional-pro-adrenomedullin, copeptin, and galectin-3 have all been well validated to predict death and heart failure following a MI and provide risk stratification information for heart failure. Rapidly developing new areas, such as assessment of micro-RNA, are also explored. All the biomarkers reflect different aspects of the development of atherosclerosis.

Successful treatment of accessory breast cancer with endocrine therapy.

Accessory breast cancers in males are extremely rare, and only a few cases have been reported in the literature. In this paper, an 87-year-old male patient was diagnosed with an accessory breast cancer by means of computed tomography (CT), magnetic resonance imaging (MRI), positron emission tomography-computed tomography (PET-CT), and immunohistochemistry based on needle biopsy, and has undergone successful resection and postoperative adjuvant endocrine therapy. He was the oldest male patient with an accessory breast cancer reported in the Chinese Hospital Knowledge Database and PubMed literature from 1975 to 2015.