The hypoxia-inducible factor EPAS1 is required for spermatogonial stem cell function in regenerative conditions.

In this study we explored the role of hypoxia and the hypoxia-inducible transcription factor EPAS1 in regulating spermatogonial stem cell (SSC) function in the mouse testis. We have demonstrated that SSCs reside in hypoxic microenvironments in the testis through utilization of the oxygen-sensing probe pimonidazole, and by confirming the stable presence of EPAS1, which is degraded at >5% O2. Through the generation of a germline-specific Epas1 knockout mouse line, and through modulation of EPAS1 levels in primary cultures of spermatogonia with the small drug molecule Daprodustat, we have demonstrated that EPAS1 is required for robust SSC function in regenerative conditions (post-transplantation and post-chemotherapy), via the regulation of key cellular processes such as metabolism. These findings shed light on the relationship between hypoxia and male fertility and will potentially facilitate optimization of in vitro culture conditions for infertility treatment pipelines using SSCs, such as those directed at pediatric cancer survivors.

Maternal diet modulates the infant microbiome and intestinal Flt3L necessary for dendritic cell development and immunity to respiratory infection.

Poor maternal diet during pregnancy is a risk factor for severe lower respiratory infections (sLRIs) in the offspring, but the underlying mechanisms remain elusive. Here, we demonstrate that in mice a maternal low-fiber diet (LFD) led to enhanced LRI severity in infants because of delayed plasmacytoid dendritic cell (pDC) recruitment and perturbation of regulatory T cell expansion in the lungs. LFD altered the composition of the maternal milk microbiome and assembling infant gut microbiome. These microbial changes reduced the secretion of the DC growth factor Flt3L by neonatal intestinal epithelial cells and impaired downstream pDC hematopoiesis. Therapy with a propionate-producing bacteria isolated from the milk of high-fiber diet-fed mothers, or supplementation with propionate, conferred protection against sLRI by restoring gut Flt3L expression and pDC hematopoiesis. Our findings identify a microbiome-dependent Flt3L axis in the gut that promotes pDC hematopoiesis in early life and confers disease resistance against sLRIs.

Comparative effectiveness of interventions for the treatment of denture stomatitis: A systematic review with network meta-analysis.

STATEMENT OF PROBLEM: Symptomatic denture stomatitis (DS) is a painful oral mucosal disorder that can impair quality of life in denture wearers. A complete cure of DS is difficult to achieve, and the most efficacious regimen to treat DS has not yet been conclusively established. PURPOSE: The purpose of this network meta-analysis was to assess the comparative efficacy of interventions used for the treatment of DS. MATERIAL AND METHODS: A search was conducted for trials published in Medline, Scopus, PubMed, and Cochrane Central Register of Controlled Trials from inception until February 2022 (PROSPERO Reg no: CRD42021271366). Network meta-analysis was performed on data from randomized controlled trials that assessed the comparative efficacy of any form of intervention for the treatment of DS in denture wearers. Agents were ranked according to their effectiveness in the treatment of DS based on outcomes using surface under the cumulative ranking (SUCRA). RESULTS: A total of 25 articles were included in the quantitative analysis. Topical antifungal agents (risk ratio [RR]=4.37[95% confidence interval [CI]: 2.15,8.90), topical antimicrobial agents used along with systemic antifungal agents (RR=4.25[95% CI: 1.79,10.33]), systemic antifungal agents (RR=4.25[95% CI: 1.79,10.10]), photodynamic therapy (RR=4.25[95% CI: 1.75,8.98]), and topical plant products (RR=3.40[95% CI: 1.59,7.26]) were found to effectively improve DS. Microwave disinfection concurrently administered with topical antifungal agents (RR=7.38(95% CI: 2.75,19.81), microwave disinfection 7.38[95% CI: 2.75,19.81]), topical antifungal agents (RR=4.88[95% CI: 1.92,12.42]), topical plant products (RR=4.49[95% CI: 1.70,11.82]), systemic antifungal agents together with topical antimicrobial agents (RR=3.85[95% CI: 1.33,11.10]), topical antimicrobial agents (RR=3.39[95% CI: 1.17,9.81]), systemic antifungal agents (RR=3.37[95% CI: 1.21,9.34]), and photodynamic therapy or photochemotherapy (PDT) (RR=2.93[95% CI: 1.01,8.47]) were found to effectively resolve mycological DS. Topical antifungals ranked highest in the SUCRA ranking for clinical improvement, whereas microwave disinfection concurrently administered with topical antifungal agents ranked highest for mycological resolution. None of the agents demonstrated significant side effects except for topical antimicrobial agents which demonstrated altered taste and staining of oral structures. CONCLUSIONS: Available evidence suggests that topical antifungals, microwave, and systemic antifungals are effective in the treatment of DS, but confidence in these findings is low because of the limited number of studies and a high risk of bias. Additional clinical trials are needed on photodynamic therapy, topical plant products, and topical antimicrobials.

Latex derived from Ficus carica L. inhibited the growth of NSCLC by regulating the caspase/gasdermin/AKT signaling pathway.

Previous studies reported the latex from the fruit of Ficus carica L. (fig) has anti-tumor and antioxidant activities in animal models. However, its active constituents, mechanism of action, and safety remain unknown. The alcohol-precipitated fraction of fig fruit latex (AFFL) was purified and prepared for testing against non-small cell lung cancer (NSCLC). UPLC-TOF-MS/MS was used to examined the components of AFFL. We validated efficacy by researching antitumor phenotypes in vitro and constructing subcutaneous grafts of nude mice with NSCLC, as well as showing the underlying mechanism at the protein level. The results showed that 11 components of AFFL were screened. AFFL significantly inhibited the proliferation, migration, invasion, and clonogenesis of NSCLC cells, promoted cell apoptosis, inhibited tumor growth in A549 xenograft mice, but induced no obvious damage to normal mouse tissues (liver or kidney). Molecular mechanism studies revealed that AFFL could increase Caspase-1 expression in cancer cells by activating the cleavage of Caspase-3 and Caspase-9, inhibiting the activity of Bcl-2, and promoting tumor cell apoptosis. These processes cause gasdermin proteins (GSDMD and GSDME) to be cleaved, releasing N-terminal domain proteins to accumulate and perforate the cell membrane, and promoting tumor cell pyroptosis. In conclusion, our findings suggested that AFFL may promote tumor cell apoptosis and pyroptosis via the Caspase/Gasdermin/AKT signaling pathway and inhibit NSCLC growth in vitro and in vivo, demonstrating that fig latex can be developed as a functional food and drug with anti-NSCLC properties.

Advances in basic research on choline and central nervous system development and related disorders / 中华预防医学杂志

Choline is an essential nutrient that plays an integral role in all stages of the life cycle, with increasing interest in the relationship between choline and neurodevelopment. Choline is a major component in the synthesis of phospholipids, phosphatidylcholine and sphingolipids, and is an essential nutrient for methyl metabolism, acetylcholine synthesis and cell signaling. Choline plays an important role in neurogenesis and neural migration during fetal development, potentially influencing the development and prognosis of neurological disorders, but its mechanism of action is not yet clear. This article reviews the source and metabolism of choline, the effects and mechanism of choline on neurodevelopment and central nervous system related disorders.

Mechanism of Astragali Radix-Curcumae Rhizoma in treating gastric cancer based on network pharmacology and experimental verification / 中国中药杂志

This study aims to investigate the mechanism of Astragali Radix-Curcumae Rhizoma(HQEZ) in the treatment of gastric cancer based on network pharmacology. Further, the SGC7901 cell model of gastric cancer was employed to validate the efficacy and key targets of the herb pair. Firstly, the CCK-8 assay was employed to evaluate the direct effect of HQEZ on the proliferation of gastric cancer SGC7901 cells. Then, network pharmacology methods were employed to investigate the active ingredients, key targets, and key signaling pathways involved in the treatment of gastric cancer with HQEZ. The results showed that HQEZ contained 18 potential active ingredients, such as quercetin, naringenin, and curcumin. The results of gene ontology(GO) functional annotation and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment suggested that the main targets of HQEZ in treating gastric cancer were involved in the regulation of protein serine/threonine kinase activity, activation of mitogen-activated protein kinase(MAPK) activity, cysteine-type endopeptidase activity, and negative regulation of protein serine/threonine kinase activity. The hypoxia-inducible factor-1(HIF-1) signaling pathway, ATP-binding cassette(ABC) transporters, cytochrome P450-mediated metabolism of xenobiotics, p53 signaling pathway, and cell apoptosis were key signaling pathways of HQEZ in treating gastric cancer. The cell experiments demonstrated that HQEZ significantly downregulated the expression of ATP-binding cassette subfamily B member 1(ABCB1), epidermal growth factor receptor(EGFR), phosphorylated serine/threonine kinase(p-AKT), hypoxia inducible factor 1 subunit alpha(HIF1A), B-cell lymphoma 2(BCL2), breast cancer susceptibility protein 1(BRCA1), DNA polymerase theta(POLH), ribonucleotide reductase M1(RRM1), and excision repair cross-complementation group 1(ERCC1), and upregulated the expression of tumor protein P53(TP53) and cysteinyl aspartate-specific proteinase(CAPS3). Finally, a multivariate COX regression model was adopted to study the relationship between gene expression and clinical information data of gastric cancer patients in the TCGA database, which demonstrated that the key targets of HQEZ were associated with the poor prognosis in gastric cancer patients. Further feature selection using the LASSO algorithm showed that EGFR, HIF1A, TP53, POLH, RRM1, and ERCC1 were closely associated with the survival of gastric can-cer patients. In conclusion, HQEZ regulates the expression of genes involved in DNA repair, survival, and apoptosis in gastric cancer cells via multiple targets and pathways, assisting the treatment of gastric cancer.

Efficacy of implantable collamer lens V4c implantation in the treatment of high myopia / 国际眼科杂志(Guoji Yanke Zazhi)

AIM:To observe the effect of implantable collamer lens V4c(ICL V4c)implantation on high myopia, and the changes in anterior segment morphology.METHODS:A prospective study was conducted on 100 patients(200 eyes)with high myopia who were treated with ICL V4c implantation in the hospital from February 2018 to March 2021. The best corrected visual acuity(BCVA), uncorrected visual acuity(UCVA), intraocular pressure, higher-order aberration, anterior segment morphology [iridocorneal angle(ICA), central anterior chamber depth(ACD), anterior chamber volume(ACV), central corneal thickness(CCT)and K-value(K)], photopic and scotopic contrast sensitivity before operation and 6 and 12mo after operation were comparatively analyzed.RESULTS:All patients were followed-up. UCVA and BCVA were significantly improved at 6 and 12mo after operation(P<0.05). Total higher-order aberration, horizontal coma and vertical coma showed no significant difference before and after operation(P>0.05). Spherical aberration, ICA, ACD and ACV at 6 and 12mo after operation were significantly smaller than those before operation(P<0.05). Under photopic state, the contrast sensitivity of 3.0 and 6.0 c/d was significantly higher at 6 and 12mo after operation when compared with that before operation(P<0.05). Under scotopic state, the contrast sensitivity of 6.0 c/d was significantly higher at 6 and 12mo after operation when compared with that before operation(P<0.05); there was no significant difference in CCT, K, or intraocular pressure before and after operation(P>0.05).CONCLUSION:Although ICA, ACD and ACV in patients with high myopia are reduced after ICL V4c implantation, the operation can effectively improve visual acuity and visual quality.

The Influence of Sintering Temperature on the Pore Structure of an Alkali-Activated Kaolin-Based Geopolymer Ceramic.

Geopolymer materials are used as construction materials due to their lower carbon dioxide (CO2) emissions compared with conventional cementitious materials. An example of a geopolymer material is alkali-activated kaolin, which is a viable alternative for producing high-strength ceramics. Producing high-performing kaolin ceramics using the conventional method requires a high processing temperature (over 1200 °C). However, properties such as pore size and distribution are affected at high sintering temperatures. Therefore, knowledge regarding the sintering process and related pore structures on alkali-activated kaolin geopolymer ceramic is crucial for optimizing the properties of the aforementioned materials. Pore size was analyzed using neutron tomography, while pore distribution was observed using synchrotron micro-XRF. This study elucidated the pore structure of alkali-activated kaolin at various sintering temperatures. The experiments showed the presence of open pores and closed pores in alkali-activated kaolin geopolymer ceramic samples. The distributions of the main elements within the geopolymer ceramic edifice were found with Si and Al maps, allowing for the identification of the kaolin geopolymer. The results also confirmed that increasing the sintering temperature to 1100 °C resulted in the alkali-activated kaolin geopolymer ceramic samples having large pores, with an average size of ~80 µm3 and a layered porosity distribution.

Application of ensemble machine learning algorithms on lifestyle factors and wearables for cardiovascular risk prediction.

This study looked at novel data sources for cardiovascular risk prediction including detailed lifestyle questionnaire and continuous blood pressure monitoring, using ensemble machine learning algorithms (MLAs). The reference conventional risk score compared against was the Framingham Risk Score (FRS). The outcome variables were low or high risk based on calcium score 0 or calcium score 100 and above. Ensemble MLAs were built based on naive bayes, random forest and support vector classifier for low risk and generalized linear regression, support vector regressor and stochastic gradient descent regressor for high risk categories. MLAs were trained on 600 Southeast Asians aged 21 to 69 years free of cardiovascular disease. All MLAs outperformed the FRS for low and high-risk categories. MLA based on lifestyle questionnaire only achieved AUC of 0.715 (95% CI 0.681, 0.750) and 0.710 (95% CI 0.653, 0.766) for low and high risk respectively. Combining all groups of risk factors (lifestyle survey questionnaires, clinical blood tests, 24-h ambulatory blood pressure and heart rate monitoring) along with feature selection, prediction of low and high CVD risk groups were further enhanced to 0.791 (95% CI 0.759, 0.822) and 0.790 (95% CI 0.745, 0.836). Besides conventional predictors, self-reported physical activity, average daily heart rate, awake blood pressure variability and percentage time in diastolic hypertension were important contributors to CVD risk classification.

Investigation on occupational hazards of non-coal mines in Hunan Province in 2021 / 中国职业医学

@#Abstract: Objective - To understand the status of occupational hazards in non coal mine mountains in Hunan Province. Methods - - A cross sectional survey was conducted on 432 non coal mining enterprises in Hunan Province in 2021. The field ， occupational health survey occupational disease hazard factors detection and occupational health monitoring data analysis were Results - carried out. Limited liability companies and private enterprises were the main economic types of non coal mining ， ， mountains in Hunan Province accounting for 55.3% and 32.4% respectively. The size of enterprises was mainly small and ， ； - micro enterprises accounting for 59.3% and 35.2% respectively 78.0% of the enterprises were in non metallic mining. The - ， over standard rates of silica dust and noise in workplaces were 17.1% and 29.4% respectively. The exposure rate of ， （P ） occupational hazard factor was 47.3%. The smaller the enterprise scale the higher the exposure rate <0.01 . The number of ， ， people exposed to silica dust and noise was the largest with the exposure rate of 29.4% and 31.0% respectively. The rates of ， occupational health training for persons in charge of enterprises occupational health management personnel and workers were ， ， ， 73.8% 73.4% and 85.0% respectively. The smaller the enterprise scale the lower the occupational health training rates of ， ， enterprise leaders occupational health management personnel and workers and the lower the implementation rates of （ P ） - - enterprise occupational health examination all <0.05 . The fully installed rate and effective rate of occupational disease ； prevention facilities were 6.9% and 1.6% respectively and the fully deployed rate and effective wearing rate of personal ， protective equipment were 11.1% and 6.2% respectively. The detection rates of occupational contraindications and suspected ， Conclusion occupational diseases in workers exposed to silica dust and noise were 2.0% and 2.9% respectively. The - ， occupational risks such as silica dust and noise are serious in non coal mine mountains of Hunan Province and the foundation of occupational health management is weak in small and micro enterprises.

Identification and attribution of chemical constituents of Qingfei Paidu Decoction based on UHPLC-LTQ-Orbitrap-MS technology / 中国中药杂志

UHPLC-LTQ-Orbitrap-MS was developed for the identification of chemical constituents in Qingfei Paidu Decoction, which will clarify its material basis. ACQUITY UHPLC HSS T3 chromatography column(2.1 mm×100 mm, 1.8 μm) was used with 0.1% formic acid(B)-acetonitrile(A) as the mobile phase in gradient elution. The decoction was detected by high-resolution liquid chromatography-mass spectrometry equipped with an ESI ion source in positive and negative mode. Based on the accurate mass measurements, retention time, mass fragmentation patterns combined with comparison of reference and literature reports, a total of 87 major compounds including 43 flavonoids, 9 alkaloids, 4 triterpenoid saponins, 1 sesquiterpene, 2 coumarins, 10 phenolic acids and 18 other compounds were tentatively screened and characterized. UHPLC-LTQ-Orbitrap-MS was employed to comprehensively elucidate the chemical components in Qingfei Paidu Decoction, which basically covered 20 Chinese medicines except gypsum in Qingfei Paidu Decoction. These collective results provide a scientific basis for further research on the quality control standard of Qingfei Paidu Decoction.

Effect of Qizhi Zhenwutang in Improving Renal Interstitial Fibrosis and Its Mechanism on Unilateral Ureteral Obstruction in Rats / 中国实验方剂学杂志

Objective:To explore the effect of Qizhu Zhenwutang on renal interstitial fibrosis in rats ligated with unilateral ureter， transforming growth factor-β1 （TGF-β1）/Smads and oxidative stress. Method:A total of 30 male SD rats were randomly divided into sham operation group， model group， high-dose group， low-dose group and irbesartan group （n=6）. The left ureter ligation was performed in the model group and the treatment group. In the sham operation group， the ureter was not ligated， only the ureter was separated， and the abdominal cavity was closed. Rats in each group were given drugs by gavage on the next day after operation. Sham operation group and model group were given aseptic distilled water 10 mL·kg-1 by gavage， high-dose Qizhizhenwu Tang group was given 22.2 g·kg-1 by gavage， low-dose group was given 11.1 g·kg-1 by gavage， and irbesartan group was given 0.02 g·kg-1 by gavage. Rats in each group were sacrificed on the 14th day after operation， 24-hour urine was collected before sampling， and the total amount of 24 hour urine protein （24 h-Upr） was detected. Blood samples were collected from the abdominal aorta to detect serum creatinine（SCr） and blood urea nitrogen （BUN）. The tissues were stained with htoxylin eosin （HE） and Masson， and the pathological changes were observed under light microscope， immunohistochemical method was used to detect α-SMA， FN and Col-Ⅰ expressions. Western blot method was used to detect the expressions of TGF-β1， Smad3， p-Smad3 and NOX4. Result:Compared with sham group， SCr， BUN and collagen volume fraction （CVF），24 h-Upr in model group were all increased （P<0.05， P<0.01）. The expressions of α-SMA， Col-Ⅰ， FN， TGF-β1， p-Smad3， NOX4 were higher （P<0.05）. Compared with the model group， SCr， BUN and CVF were lower in high-dose group and irbesartan group （P<0.05）. 24 h-Upr was lower in high-dose group （P<0.05）， the expressions of α-SMA， Col-Ⅰ， FN， TGF-β1， Smad3， p-Smad3， NOX4 in traditional Chinese medicine treatment group were less （P<0.05）. Conclusion:Qizhi Zhenwutang can reduce the urinary protein of UUO rats， protect the renal function， and inhibit the occurrence and development of renal interstitial fibrosis， the mechanism may be related to the inhibition of TGF-β1/Smads signaling pathway and oxidative stress response.

The correlation between hyperhomocysteinemia and hyperuricemia in the population undergoing physical examination / 中华健康管理学杂志

Objective:To investigate the correlation between hyperhomocysteinemia (HCA) and hyperuricemia (HUA).Methods:A total of 8 465 individuals who received a medical examination at the Xiangya Hospital Health Management Center of Central South University were selected as research subjects from January to June 2018. The multi-factor binary Logic regression method was adopted and four different models. The ratio ( OR) and its 95% trusted interval ( CI) between Hhcy group and normal control group were analyzed. Results:Compared to the normal control group, the OR(95% CI) of the probability of HUA in the Hhcy population was 3.272 (95% CI: 2.839 to 3.771, P<0.001) without correcting other factors; After correcting the influence of age and gender, the OR (95% CI) of the Hhcy population with HUA probability was 2.111 (95% CI: 1.811-2.461, P<0.001); After correcting age, gender, Body Mass Index (BMI), blood pressure, fasting blood sugar, triglycerin, low-density lipoprotein, and high-density lipoprotein, the OR(95% CI) of the Hhcy population with HUA probability was 2.163 (95% CI: 1.845 to 2.535, P<0.001); After correcting age, sex, BMI, blood pressure, fasting blood sugar, triglycerin, low-density lipoprotein, high-density lipoprotein, drinking, smoking, exercise time, and exercise intensity, the OR (95% CI) of the Hhcy population had a HUA probability of 2.209(95% CI: 1.845 to 2.646, P<0.001). Conclusion:The cross-sectional study confirmed that Hhcy was positively correlated with HUA. Reducing homocysteine levels may be a new approach to the health management of HUA.

Effects of fluorine exposure on miR-204 and BDNF-TrkB pathways in HT22 hippocampal neurons / 中华地方病学杂志

Objective:To explore the changes of microRNA (miRNA, miR)-204, brain-derived neurotrophic factor (BDNF) and tyrosine kinase receptor B (TrkB) expression levels in HT22 hippocampal neurons exposed to fluorine.Methods:The HT22 cells were exposed to NaF at 0, 2, 4, 6, 8, 10 mg/L. After 24 h, the cell viability was detected by CCK-8. According to the cell survival rate, the NaF concentrations [0.0 (control), 2.5, 5.0 and 10.0 mg/L] were selected for subsequent experiments. The infected (without transfection) and transfected (with the addition of miR-204 agonist) HT22 cells were both exposed to NaF for 24 h. The miR-204, BDNF and TrkB mRNA expression levels in cells were detected by Real time fluorescence quantitative PCR(qRT-PCR); the BDNF and TrkB protein expression levels in cells were detected by Western blotting.Results:Compared with the control group, the cell viabilities in fluorine exposure groups were decreased ( P < 0.01). In the infected groups, compared with the control group, and the miR-204 expression levels were increased ( P < 0.05 or < 0.01). The expressions of BDNF mRNA were decreased in fluorine exposure groups at 5.0 and 10.0 mg/L ( P < 0.01) and the BDNF protein expressions were decreased in all fluorine exposure groups ( P < 0.05 or < 0.01). In the exposure groups, TrkB mRNA expressions were decreased ( P < 0.05 or < 0.01). The TrkB protein expressions were decreased in fluorine exposure groups at 5.0 and 10.0 mg/L ( P < 0.01). In the transfected groups, compared with the control group, the expressions of miR-204 were increased ( P < 0.01) and the mRNA and protein expressions of BDNF and TrkB were decreased ( P < 0.01). The negative correlation was found between NaF concentration and cell survival rate ( r = - 0.989, P < 0.01). Moreover, the mRNA and protein expressions of BDNF and TrkB were negative correlated with NaF concentration ( r = - 0.746, - 0.853, - 0.889, - 0.827, P < 0.01). A positive correlation was found between NaF concentration and miR-204 expression ( r = 0.889, P < 0.01). However, the mRNA and protein expressions of BDNF and TrkB were negative correlated with miR-204 expression ( r = - 0.766, - 0.770, - 0.594, - 0.523, P < 0.01). The positive correlations were found between BDNF mRNA and protein expressions and those of TrkB ( r = 0.657, 0.869, P < 0.01). Conclusion:Fluorine has inhibited the cell activity of HT22, and the mechanism of action may be related to the inhibition of BDNF-TrkB pathway after up-regulation of miR-204 expression.

Clinical value of contrast-enhanced ultrasound and gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid-enhanced magnetic resonance imaging in the diagnosis of hepatocellular carcinoma / 中华消化外科杂志

Objective:To investigate the clinical value of contrast-enhanced ultrasound and gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid-enhanced magnetic resonance imaging (Gd-EOB-DTPA MRI) in the diagnosis of hepatocellular carcinoma (HCC).Methods:The clinically diagnostic test was conducted. The clinicopathological data of 274 lesions in 250 patients with liver neoplasms who were admitted to the First Hospital Affiliated to Army Medical University from January 2017 to December 2018 were collected. There were 204 males and 46 females, aged (52±11)years, with a range from 22 to 78 years. Patients underwent contrast-enhanced ultrasound and Gd-EOB-DTPA MRI, and they received surgical resection or biopsy within one month. Images was read and analyzed by two senior radiologists for diagnosis. Observation indicators: (1) imaging features of contrast-enhanced ultrasound and Gd-EOB-DTPA MRI, including ① imaging features of contrast-enhanced ultrasound, ② imaging features of Gd-EOB-DTPA MRI, ③ enhanced imaging manifestation in different phases of 223 HCC lesions; (2) dignostic performance of contrast-enhanced ultrasound, Gd-EOB-DTPA MRI, or the combined examinations for HCC diagnosis, including ① sensitivity, specificity and accuracy rate of the three methods for HCC diagnosis and ② sensitivity, specificity and accuracy rate of the three methods for HCC diagnosis in lesions with different diameters. Count data were represented as absolute numbers or percentages, and comparison between groups was analyzed using the chi-square test or Fisher exact probability. With the pathological examination as the golden criteria of diagnosis, the sensitivity, specificity and accuracy rate of the contrast-enhanced ultrasound, Gd-EOB-DTPA MRI, or the combined examinations for HCC diagnosis were calculated.Results:(1) Imaging features of contrast-enhanced ultrasound and Gd-EOB-DTPA MRI. ① Imaging features of contrast-enhanced ultrasound: of the 223 HCC lesions on contrast-enhanced ultrasound, 167 lesions were accorded with fast in fast out of HCC, 7 were missed diagnosed and 49 were misdiagnosed. Of the 51 non-HCC lesions on contrast-enhanced ultrasound, 7 lesions were accorded with fast in fast out, including 3 of combined hepatocellular-cholangiocarcinoma, 2 of intrahepatic cholangiocarcinoma, 1 of neuroendocrine tumor, 1 of inflammatory granuloma, 44 lesions were no fast in fast out. ② Imaging features of Gd-EOB-DTPA MRI: of the 223 HCC lesions on Gd-EOB-DTPA MRI, 178 lesions were accorded with fast in fast out of HCC, 1 was missed diagnosed and 44 were misdiagnosed. Of the 51 non-HCC lesions on Gd-EOB-DTPA MRI, 5 lesions were accorded with fast in fast out, inlcuding 2 of intrahepatic cholangiocarcinoma, 1 of combined hepatocellular-cholangiocarcinoma, 1 of neuroendocrine tumor, 1 of inflammatory granuloma, 46 lesions were no fast in fast out. ③ Enhanced imaging manifestation in different phases of 223 HCC lesions. In arterial phase, 92.83%(207/223) of the lesions displayed hyper-enhanced on contrast-enhanced ultrasound, and 80.72%(180/223) of the lesions displayed hyper-enhanced on Gd-EOB-DTPA MRI, showing a significant difference ( χ2=14.240, P<0.05). In portal vein phase or late phase, 78.48%(175/223) of the lesions displayed hypo-enhanced on contrast-enhanced ultrasound, and 96.41%(215/223) of the lesions displayed hypo-enhanced on Gd-EOB-DTPA MRI, showing a significant difference ( χ2=32.674, P<0.05). On Gd-EOB-DTPA MRI, 96.41%(215/223) of the lesions displayed low signals in portal-vein phase or late phase, and 98.21%(219/223) of the lesions displayed low signals in hepatobiliary phase, showing no significant difference ( χ2=1.370, P>0.05). (2) Dignostic performance of contrast-enhanced ultrasound, Gd-EOB-DTPA MRI, or the combined examinations for HCC diagnosis. ① Sensitivity, specificity and accuracy rate of the three methods for HCC diagnosis: the sensitivities of contrast-enhanced ultrasound, Gd-EOB-DTPA MRI, or the combined examinations for HCC diagnosis were 74.89%(167/223), 79.82%(178/223), 94.62%(211/223), respectively. The specificities of contrast-enhanced ultrasound, Gd-EOB-DTPA MRI, or the combined examinations for HCC diagnosis were 86.27%(44/51), 90.20%(46/51), 80.39%(41/51). The accuracy rates of contrast-enhanced ultrasound, Gd-EOB-DTPA MRI, or the combined examinations for HCC diagnosis were 77.01%(211/274), 81.75%(224/274), 91.97%(252/274). There were significant differences in the sensitivity and accuracy rate among the three methods ( χ2=33.499, 23.345, P<0.05). There was no significant difference in the specificity among the three methods ( χ2=2.017, P>0.05). ② Sensitivity, specificity and accuracy rate of the three methods for HCC diagnosis in lesions with different diameters: 128 of 274 lesions had the maximun diameter>3 cm and ≤5 cm, 92 lesions had the maximun diameter >2 cm and ≤3 cm, 54 lesions had the maximun diameter≤ 2 cm. The sensitivities of contrast-enhanced ultrasound for HCC diagnosis in lesions with the maximun diameter>3 cm and ≤5 cm, >2 cm and ≤3 cm, ≤2 cm were 81.19%(82/101), 76.92%(60/78), 56.82%(25/44), the specificities were 92.59%(25/27), 71.43%(10/14), 90.00%(9/10), and the accuracy rates were 83.59%(107/128), 76.09%(70/92), 62.96%(34/54), respectively. The sensitivities of Gd-EOB-DTPA MRI for HCC diagnosis in lesions with the maximun diameter>3 cm and ≤5 cm, >2 cm and ≤3 cm, ≤2 cm were 83.17%(84/101), 79.49%(62/78), 72.73%(32/44), the specificities were 96.30%(26/27), 85.71%(12/14), 80.00%(8/10), and the accuracy rates were 85.94%(110/128), 80.43%(74/92), 74.07%(40/54), respectively. The sensitivities of contrast-enhanced ultrasound combined with Gd-EOB-DTPA MRI for HCC diagnosis in lesions with the maximun diameter>3 cm and ≤5 cm, >2 cm and ≤3 cm, ≤2 cm were 95.05%(96/101), 96.15%(75/78), 90.91%(40/44), the specificities were 92.59%(25/27), 57.14%(8/14), 80.00%(8/10), and the accuracy rates were 94.53%(121/128), 90.22%(83/92), 88.89%(48/54), respectively. There were significant differences in the sensitivities for HCC diagnosis in lesions with the maximun diameter>3 cm and ≤5 cm, >2 cm and ≤3 cm, ≤2 cm among the three methods ( χ2=9.703, 12.777, 13.142, P<0.05). There were also significant differences in the accuracy rates ( χ2=8.051, 6.600, 9.826, P<0.05). There was no significant difference in the specificies ( P>0.05). Conclusions:There was no significant difference in the dignostic performance for HCC diagnosis between contrast-enhanced ultrasound and Gd-EOB-DTPA MRI, and the combination of contrast-enhanced ultrasound and Gd-EOB-DTPA MRI can improve the diagnostic sensitivity and accuracy rate of HCC.

Clinical predictive value of TCD in monitoring cerebral circulation in sepsis patients / 中华急诊医学杂志

Objective:To study the dynamic evaluation value of transcranial Doppler (TCD) in cerebral circulation and brain function of sepsis patients and its predictive value of the prognosis.Methods:A retrospective analysis was performed on 98 sepsis patients admitted to our hospital from January 2017 to June 2018 who were divided into the survival group (56 cases) and death group (42 cases) according to the 28-day prognosis. The general clinical data of the patients, acute physiology and chronic health evaluation II (APACHE II), delirium assessment scale (CAM-ICU), and TCD parameters PSV, Vm, EDV, PI, RI on the first day and the third day of admission were collected, and the differences of TCD parameters at different time points were analyzed between the two groups, the area under the ROC curve (AUC) was calculated and evaluating their predictive value of sepsis outcome was evaluated.Results:APACHE Ⅱscore and the number of patients with sepsis encephalopathy were significantly higher in the death group than those in the survival group ( P < 0.05). There were no significant differences in PSV, Vm and EDV between the two groups on the first day and the third day. The PI and RI of the survival group were significantly lower than those of the death group ( P<0.01). In the survival group, PI and RI on the third day decreased significantly compared with those on the first day ( P < 0.05), while in the death group, PI and RI on the first day and the third day did not change significantly. ROC survival curves showed that Day1PI, Day3PI, Day1PI - Day3PI, Day1RI, Day3RI, Day1RI - Day3RI and APACHEⅡ predicted AUC of the prognosis of sepsis patients were 0.657, 0.835, 0.730, 0.707, 0.826, 0.705, and 0.815 ( P < 0.01). When PI cutoff value on the third day became 1.02, the sensitivity was 85.7% and the specificity was 61.3%. When RI cutoff value on the third day became 0.62, the sensitivity was 78.6% and the specificity was 71.4%. Conclusions:TCD parameters, PI and RI, are of certain value in the dynamic evaluation of cerebral circulation and brain function in sepsis patients. PI and RI on the first day and the third day and the differences between them are all valuable in predicting the prognosis, and PI and RI on the third day have greater predictive value.

Current Status on Immunological Therapies for Type 1 Diabetes Mellitus.

PURPOSE OF REVIEW: Type 1 diabetes (T1D) occurs when there is destruction of beta cells within the islets of Langerhans in the pancreas due to autoimmunity. It is considered a complex disease, and different complications can surface and worsen the condition if T1D is not managed well. Since it is an incurable disease, numerous treatments and therapies have been postulated in order to control T1D by balancing hyperglycemia control while minimizing hypoglycemic episodes. The purpose of this review is to primarily look into the current state of the available immunological therapies and their advantages for the treatment of T1D. RECENT FINDINGS: Over the years, immunological therapy has become the center of attraction to treat T1D. Immunomodulatory approaches on non-antigens involving agents such as cyclosporine A, mycophenolate mofetil, anti-CD20, cytotoxic T cells, anti-TNF, anti-CD3, and anti-thymocyte globulin as well as immunomodulative approaches on antigens such as insulin, glutamic acid decarboxylase, and heat shock protein 60 have been studied. Aside from these two approaches, studies and trials have also been conducted on regulatory T cells, dendritic cells, interleukin 2, interleukin 4, M2 macrophages, and rapamycin/interleukin 2 combination therapy to test their effects on patients with T1D. Many of these agents have successfully suppressed T1D in non-obese diabetic (NOD) mice and in human trials. However, some have shown negative results. To date, the insights into the management of the immune system have been increasing rapidly to search for potential therapies and treatments for T1D. Nevertheless, some of the challenges are still inevitable. A lot of work and effort need to be put into the investigation on T1D through immunological therapy, particularly to reduce complications to improve and enhance clinical outcomes.

The value of left atrial structural and functional parameters combined with cardiac biomarkers in predicting left atrial spontaneous echo contrast in patients with non‐valvular atrial fibrillation / 中华超声影像学杂志

Objective To investigate the relationships between the structure ,function of left atrial as well as cardiac biomarkers and left atrial spontaneous echo contrast ( SEC ) in patients with non‐valvular atrial fibrillation ( NVAF ) ,and evaluate its predictive value for left atrial SEC . Methods T hirty‐four control subjects and 80 patients with NVAF were included ,patients with NVAF were divided into positive group ( 30 cases) and negative group ( 50 cases) according to w hether SEC was presented on transesophageal echocardiography ( T EE ) . Clinical and laboratory data were collected ,including medical history ,cardiac troponin I ( cT nI) ,and pro‐brain natriuretic peptide ( pro‐BNP ) ,etc . T hen CHA2 DS2‐VASc scores were calculated .The left atrial appendage width ( W LAA ) ,left atrial appendage depth ( DLAA ) ,left atrial appendage blood flow velocity ( V LAA ) ,left atrial volume index ( LAVI) and other parameters were measured by T EE and transthoracic echocardiography ( T T E) ,and left atrial ejection fraction ( LAEF ) was calculated . T he clinical and T EE parameters were compared between the positive and negative group ,T T E parameters and cardiac biomarkers levels were compared among the three groups ,and ROC curve was used to evaluate the diagnostic efficiency . Results ①Compared with those in control group ,the value of LAVI and pro‐BNP were significantly increased and LAEF was significantly decreased in negative group ( all P ＜ 0 .01 ) . ②Compared with those in negative group ,CHA 2 DS2‐VASc scores ,WLAA ,DLAA ,LAVI and pro‐BNP levels in positive group showed a significant increase ( all P ＜0 .01) ,LAEF and VLAA showed a significant reduction ( all P ＜0 .01) . ③cT nI between negative group and control group did not show statisticant difference ( P＞0 .05) ,but presented a significant increase in positive group compared with those in control group and negative group (all P ＜0 .01).T he AUC ,sensitivity and specificity of CHA 2 DS2‐VASc scores for SEC were 0 .71 (95% CI :0 .60 ～ 0 .82 ) ,73 .3% and 62 .0%,respectively .When left atrial structural and functional parameters (LAVI and LAEF ) combined with cardiac biomarkers (cT nI and pro‐BNP ) ,the AUC , sensitivity and specificity for SEC were 0 .90 (95% CI :0 .84 ～ 0 .97 ) ,74 .0% and 100%,respectively ,both enhanced w hen compared with CHA 2 DS2‐VASc scores alone ( P ＜ 0 .01 ).Conclusions Left atrial enlargement ,decreased function and elevated levels of cardiac biomarkers are associated with left atrial SEC in patients with NVAF .CHA2 DS2‐VASc scores can be used for perdicting left atrial SEC ,left atrial structural and functional parameters (LAVI and LAEF) combined with cardiac biomarkers (cT nI and pro‐BNP) provide significant increments in prediction of left atrial SEC .

Association between serum copper concentration and hypertension in knee osteoarthritis patients / 中南大学学报(医学版)

To examine the association between serum copper concentration and the prevalence of hypertension in patients with knee osteoarthritis (OA).
 Methods: A total of 935 patients who were aged ≥40 years and underwent routine checkups from October 2013 to November 2014 at the Health Management Center of Xiangya Hospital, Central South University were included. They were diagnosed as knee OA by weight-bearing bilateral anteroposterior radiography. Serum copper concentration was measured using the chemiluminescence method. Blood pressure was measured by an electronic sphygmomanometer. The association between serum copper concentration and hypertension was evaluated by conducting multivariable adjusted logistic regression.
 Results: Compared with the lowest quintile, the multivariable-adjusted odds ratio (OR) and related 95% confidence interval (95% CI) of hypertension were 1.46 (95% CI 1.02 to 2.09, P for trend=0.035) and 1.47 (95% CI 0.77 to 2.78, P for trend=0.032) in the total population and female subgroup of the highestest quintile, respectively. There was no significant association between serum copper and hypertension in male subgroup among OA patients (OR=1.21, 95% CI 0.76 to 1.93, P for trend=0.354).
 Conclusion: The serum copper concentration was significantly associated with the prevalence of hypertension in total population and female subgroup, but may not in male subgroup among patients with knee OA.

Lung cancer screening with low-dose spiral CT in a unit staff: Results of the baseline screening / 中南大学学报(医学版)

To analyze the incidence and imaging characteristics of pulmonary nodules in a unit staff.
 Methods: Low-dose spiral CT (LDCT) scan were performed in 1 372 staffs ≥45 years old in a certain unit during the physical examination. The clinical and imaging data were collected to analyze the detection rate, imaging characteristics, and postoperative pathological conditions of pulmonary nodules.
 Results: The total detection rate for pulmonary nodules was 30.39% (417/1 372). The detected nodules were mainly single (227 cases), solid (343 cases), 0.05). Compared with the Lung-RADS category 3 nodules, the proportions of nodules in subsolid state, with irregular shape, lobulation sign, and vascular penetration in the Lung-RADS category 4 were increased (all P<0.05). Among them, 11 patients received surgical therapy, including 10 women. Postoperative pathology confirmed lung adenocarcinoma in 9 patients (2.16%), including 8 women, all non-smokers.
 Conclusion: The nodules in subsolid state with vascular penetration, irregular shape and lobulation sign tend to be malignant. Lung cancer screening with low-dose spiral CT in female non-smokers should be emphasized.