Fenofibrate alleviates NAFLD by enhancing the PPARα/PGC-1α signaling pathway coupling mitochondrial function.

BACKGROUND: To comprehend the influences of fenofibrate on hepatic lipid accumulation and mitochondrial function-related signaling pathways in mice with non-alcoholic fatty liver disease (NAFLD) secondary to high-fat diets together with free fatty acids-influenced HepG2 cells model. MATERIALS AND METHODS: A random allocation of male 6-week C57BL/6J mice into three groups was done, including controls, model (14 weeks of a high-fat diet), and fenofibrate [similar to the model one with administered 0.04 g/(kg.d) fenofibrate by gavage at 11 weeks for 4 weeks] groups, which contained 10 mice each. This study verified NAFLD pathogenesis via mitochondrial functions in hepatic pathological abnormalities, liver index and weight, body weight, serum biochemical indexes, oxidative stress indicators, mitochondrial function indexes, and related signaling pathways. The effect of fenofibrate intervention was investigated in NAFLD model mice. In vitro, four groups based on HepG2 cells were generated, including controls, the FFA model (1.5 mmol/L FFA incubation for 24 h), LV-PGC-1α intervention (similar to the FFA model one after PPARGC1A lentivirus transfection), and LV control intervention (similar to the FFA model one after negative control lentivirus transfection) groups. The study investigated the mechanism of PGC-1α related to lipid decomposition and mitochondrial biosynthesis by Oil red O staining, colorimetry and western blot. RESULTS: In vivo experiments, a high-fat diet achieved remarkable changes regarding liver weight, liver index, serum biochemical indicators, oxidative stress indicators, liver pathological changes, mitochondrial function indicators, and body weight of the NAFLD model mice while fenofibrate improved the objective indicators. In the HepG2 cells model, the lipid accumulation increased significantly within the FFA model group, together with aggravated hepatocytic damage and boosted oxidative stress levels. Moreover, FFA induced excessive mitosis into fragmented in mitochondrial morphology, ATP content in cells decreased, mtDNA replication fold decreased, the expression of lipid decomposition protein PPARα reduced, mitochondrial biosynthesis related protein PGC-1α, NRF-1 and TFAM decreased. PGC-1α overexpression inhibited lipid deposition by improving mitochondrial biosynthesis and lipid decomposition. CONCLUSION: Fenofibrate up-regulated PPARα/PGC-1α signaling pathway, promoted mitochondrial ß-oxidation, reduced oxidative stress damage and lipid accumulation of liver. PGC-1α overexpression enhanced mitochondrial biosynthesis and ATP production, and reduced HepG2 intracellular accumulation of lipids and oxidative stress.

Application of Xiao Chaihutang in Whole Process Management of Malignant Tumors： A Review / 中国实验方剂学杂志

Malignant tumors have surpassed stroke and coronary heart disease to become the main cause of death before the age of 70 in the world. The incidence of malignant tumors is increasing year by year， which seriously affects the living standards and social and economic development of Chinese people. Surgery， radiotherapy， chemotherapy， targeted therapy， and immunotherapy are the main means of Western medicine to intervene in tumors， which are of great significance for prolonging the survival time of patients. However， there are many disadvantages such as adverse reactions and drug resistance. Traditional Chinese medicine has become a research hotspot in recent years because of its definite curative effect and wide application in tumor treatment. Xiao Chaihutang is derived from the Treatise on Febrile and Miscellaneous Diseases. It is composed of Bupleuri Radix， Scutellariae Radix， Ginseng Radix， Pinelliae Rhizoma， Glycyrrhizae Preparata Radix， Ginger， and Jujube. It has the effects of reconciling Shaoyang， reconciling cold and heat Yin and Yang， soothing the liver， and relieving depression. This prescription and the prescriptions based on it are widely used in various stages of tumors. This study summarized the Chinese and foreign research of Xiao Chaihutang in the field of tumors in the past 10 years and explored the role and mechanism of Xiao Chaihutang in blocking precancerous lesions， controlling the development of malignant tumors， reducing the occurrence of adverse reactions after intervention， and alleviating common complications， with a view to expanding the clinical medication ideas.

Adult-onset idiopathic hypogonadotropic hypogonadism: An evaluation of the diagnosis and treatment for three cases / 中华内分泌代谢杂志

Objective:To investigate the clinical characteristics and offer diagnostic and therapeutic approaches for adult-onset idiopathic hypogonadotropic hypogonadism(AIHH).Methods:Clinical, laboratory, and imaging data, as well as follow-up information, of three male patients diagnosed with AIHH at the Department of Endocrinology and Metabolism of Nanfang Hospital, Southern Medical University, were systematically reviewed and analyzed.Results:All three patients were male, with a median age of 39 years(range, 22 to 40). Two patients reported symptoms of enlarged breasts and reduced sexual function, while one case solely reported a decline in sexual function. Physical examination showed that the median length of the penis was 6 cm(range, 5 to 6 cm), and the bilateral testicular volume was 7.96 mL(4.70-8.82 mL). Basal hormone levels at the time of initial visit to our hospital as follows: the median testosterone level was 0.32 ng/mL(0.24-2.96 ng/mL), median follicle stimulating hormone(FSH) level was 0.56 mIU/mL(0.1-0.75 mIU/mL), and the median luteinizing hormone(LH) level was 0.69 mIU/mL(0.1-1.03 mIU/mL). The levels of other hormones secreted by the anterior pituitary gland were normal. Hypothalamic-pituitary magnetic resonance imaging(MRI) showed that 1 patient had a pituitary microadenoma. Three patients were treated with pulsatile GnRH or gonadotropins, one of which had hypothalamic-pituitary-gonadal(HPG) axis function reversal after GnRH pulse pump therapy and lasted for 1 year, but then still had irreversible reduction.Conclusion:AIHH is marked by adult-onset disease and idiopathic hypogonadism. Enhancing fertility remains a critical requirement for these patients. Pulsatile GnRH treatment or gonadotropin therapy, as viable treatments, exhibit therapeutic effects, albeit with occasional fluctuations. Therefore, the emphasis lies in the timely consideration of fertility preservation.

Research progress in strigolactones and application prospect in medicinal plants / 中国中药杂志

Strigolactones(SLs) are a class of sesquiterpenoids derived from the carotenoid biosynthesis pathway with the core carbon skeleton consisting of tricyclic lactone(ABC tricyclic ring) and α,β-unsaturated furan ring(D ring). SLs are widely distributed in higher plants and are symbiotic signals between plants and Arbuscular mycorrhiza(AM), which play key roles in the evolution of plant colonizing terrestrial habitats. As a new type of plant hormone, SLs possess such important biological functions as inhibiting shoot branching(tillers), regulating root architecture, promoting secondary growth, and improving plant stress resistance. Therefore, SLs have attracted wide attention. The biological functions of SLs are not only closely related to the formation of "excellent shape and quality" of Chinese medicinal materials but also have important practical significance for the production of high-quality medicinal materials. However, SLs have been currently widely studied in model plants and crops such as Oryza sativa and Arabidopsis thaliana, and few related studies have been reported on SLs in medicinal plants, which need to be strengthened. This review focused on the latest research progress in the isolation and identification, biological and artificial synthesis pathways, biosynthesis sites and transport modes, signal transduction pathways and mechanisms, and biological functions of SLs, and prospected the research on the regulation mechanism of SLs in the growth and development of medicinal plants and their related application on targeted regulation of Chinese herbal medicine production, which is expected to provide some references for the in-depth research on SLs in the field of Chinese medicinal resources.

Application of strigolactone analogs in storage of Gastrodia elata / 中国中药杂志

This study explored the preservation effect of strigolactone analogs on Gastrodia elata tubers and screened out the suitable preservation measures of G. elata to provide a safer and more effective method for its storage and preservation. Fresh G. elata tubers were treated with 7FGR24, 2,4-D isooctyl ester, and maleic hydrazide, respectively. The growth of flower buds, the activities of CAT, and MDA, and the content of gastrodin and p-hydroxybenzyl alcohol were measured to compare the effects of different compounds on the storage and preservation of G. elata. The effects of different storage temperatures on the preservation of 7FGR24 were compared and analyzed. The gibberellin signal transduction receptor gene GeGID1 was cloned, and the effect of 7FGR24 on the expression level of GeGID1 was analyzed by quantitative polymerase chain reaction(qPCR). The toxicity of the G. elata preservative 7FGR24 was analyzed by intragastric administration in mice to evaluate its safety. The results showed that compared with 2,4-D isooctyl ester and maleic hydrazide, 7FGR24 treatment had a significant inhibitory effect on the growth of G. elata flower buds, and the CAT enzyme activity of G. elata was the highest, indicating that its preservation effect was stronger. Different storage temperatures had different effects on the preservation of G. elata, and the preservation effect was the strongest at 5 ℃. The open reading frame(ORF) of GeGID1 gene was 936 bp in length, and its expression level was significantly down-regulated after 7FGR24 treatment, indicating that 7FGR24 may inhibit the growth of flower buds by inhibiting the gibberellin signal of G. elata, thereby exerting a fresh-keeping effect. Feeding preservative 7FGR24 had no significant effect on the behavior and physiology of mice, indicating that it had no obvious toxicity. This study explored the application of the strigolactone analog 7FGR24 in the storage and preservation of G. elata and preliminarily established a method for the storage and preservation of G. elata, laying a foundation for the molecular mechanism of 7FGR24 in the storage and preservation of G. elata.

Zuogui Pills and Yougui Pills in differential treatment of diminished ovarian reserve based on metabolomics / 中国中药杂志

Based on the metabolomics, this paper systematically analyzed the metabolic substance basis of Zuogui Pills and Yougui Pills in syndrome differentiation and treatment of diminished ovarian reserve(DOR), so as to provide a scientific basis for the traditional Chinese medicine(TCM) syndrome differentiation and treatment of DOR. Patients with DOR of kidney-Yin deficiency syndrome were collected from outpatient department of hospitals and treated with Zuogui Pills for 12 weeks. And kidney-Yang deficiency syndrome were treated with Yougui Pills for 12 weeks. Based on the non-targeted metabolomic research techniques, the potential biomarkers of Zuogui Pills and Yougui Pills in the treatment of DOR with kidney-Yin deficiency and kidney-Yang deficiency, respectively, were screened out, and metabolic pathways of biomarkers were analyzed. The pregnancy rate, basic serum hormone levels [basal follicle-stimulating hormone(bFSH), basal-luteinizing hormone(bLH), basal-estradiol(bE_2), and anti-Müllerian hormone(AMH)], TCM syndrome type score, and Kupperman score were recorded and statistically analyzed after treatment. The results showed that 23 patients with DOR of kidney-Yin deficiency syndrome and 25 patients of kidney-Yang deficiency syndrome were collected. Twenty-six differential metabolites, including L-carnitine, acetyl-CoA, coenzyme A, and coenzyme Q_(10)(CoQ10), were mapped to 12 metabolic pathways in patients with kidney-Yin deficiency treated with Zuogui Pills. Twenty-two differential metabolites, such as adipoyl-CoA, L-lysine, lysine arginine, and α-tocopherol, were mapped to 11 metabolic pathways in patients with kidney-Yang deficiency. After treatment, bFSH and bLH of patients with DOR were significantly lower than those before treatment(P<0.05). Although the comparison of bE_2 and AMH had no significant differences, there was a improvement trend. The TCM syndrome type score and Kupperman score of patients with DOR after TCM treatment were significantly lower than those before treatment(P<0.05).

The predictive value of warning scores for intensive care unit admission in coronavirus disease 2019 patients / 中华内科杂志

To evaluate the predictive value of early warning scores for intensive care unit (ICU) admission in patients with coronavirus disease 2019 (COVID-19). For COVID-19 patients who were admitted to Shijiazhuang People's Hospital from January 2021 to February 2021, national early warning score (NEWS), national early warning score 2 (NEWS2), rapid emergency medicine score (REMS), quick sepsis-related organ failure (qSOFA), altered consciousness, blood urea nitrogen, respiratory rate, blood pressure, and age-65 (CURB-65) were used to evaluate the inpatient condition and the predictive value for ICU admission. A total of 368 patients were included, and 32 patients (8.7%) were transferred to the ICU. The median age was 49.0 (34.0,61.0) years. The scores of NEWS, NEWS2, REMS, and CURB-65 were 1 (0, 2), 1 (0, 2), 4 (2, 6) and 0 (0, 1), respectively. The receiver operating characteristic (ROC) cure (AUC) was used to evaluate the predictive value in detecting patients who are at risk of being transferred to the ICU. Area under the ROC AUC of NEWS was 0.756, sensitivity 65.6%, and specificity 71.3%. ROC AUC of NEWS2 was 0.732, sensitivity 62.5%, and specificity 61.3%. ROC AUC of REMS was 0.787, sensitivity 84.4%, and specificity 64.6%. ROC AUC of CURB-65 was 0.814, sensitivity 81.3%, and specificity 76.8%. The predictive value of NEWS and NEWS2 combined with age were significantly improved. The ROC AUC of NEWS combined with age was 0.885, sensitivity 85.1%, and specificity 75.0%. The ROC AUC of NEWS2 combined with age was 0.883, sensitivity 84.2%, and specificity 75.0%. NEWS and NEWS2 combined with age can be used as a predictive tool for whether COVID-19 patients will be admitted to the ICU.

ffects of Zuogui Pills on kidney-yin deficiency syndrome of premature ovarian insufficiency rats / 国际中医中药杂志

Objective:To study the effects of Zuogui Pills on rats with kidney-yin deficiency syndrome of premature ovarian insufficiency.Methods:Totally 40 SD female unmated rats were randomly divided into blank group, model group, Zuogui Pills group and Bujiale group, with 10 rats in each group. Except for blank group, rats in other groups were subcutaneously injected with ZP3 and gavaged with levothyroxine sodium to induce kidney-yin deficiency syndrome model of premature ovarian insufficiency. At the same time of modeling, Zuogui Pills group and Bujiale group received corresponding drugs for gavage, and the other groups received corresponding solvent for gavage, once a day, for consecutive 21 days. On day 0, 7, 14 and 21, ear temperature and body weight of rats were measured, and the ovarian index, uterus index and thyroid index were calculated. Serum levels of adenosine cyclic phosphate (cAMP), cyclic guanosine phosphate (cGMP), Cortisol, follicle-stimulating hormone (FSH), luteinizing hormone (LH) and estradiol (E 2) were detected by ELISA. Pathological changes of ovary was observed with HE staining. Results:On day 14 and 21, compared with model group, the body weight of rats in Zuogui Pills group increased ( P<0.05), and the ear temperature decreased ( P<0.05); compared with model group, the ovarian index, uterine index and thyroid index of rats in Zuogui Pills group decreased ( P<0.05), the levels of serum cAMP/cGMP, cortisol, FSH and LH decreased ( P<0.05), and the level of E 2 increased ( P<0.05). Conclusion:Zuogui Pills have certain improvement effect on rats with kidney-yin deficiency syndrome induced by levothyroxine sodium tablets combined with ZP3.

Evaluation of teaching effect of opening experiments on occupational health and occupational medicine / 中华医学教育探索杂志

Objective:To carry out opening experiments on occupational health and occupational medicine for students majoring in preventive medicine, reform the experimental teaching mode, and explore the teaching methods to improve students' professional quality and scientific research ability.Methods:Opening experiments were carried out in the experimental course of occupational health and occupational medicine for students of preventive medicine major. A total of 147 students majoring in preventive medicine of Batch 2016 were classified as the control group, and the routine confirmatory experiment was carried out in the group; 176 students majoring in preventive medicine of Batch 2017 were classified as the experimental group, and this group carried out opening experiment. The evaluation was made from three aspects: comprehensive evaluation results, teacher self-evaluation and student satisfaction survey. SPSS 22.0 software was used for analysis and comparison by independent-samples t-test and Chi-square test. Results:The theoretical scores of the experimental group and the control group students were (84.37±10.45) vs. (81.44±9.22) ( t=2.68, P=0.008), and the experimental skills scores were (93.66±3.89) vs. (88.41±5.67) ( t=9.51, P<0.001). Questionnaire investigation showed that the students in the opening experimental group were more satisfied with the courses arrangement ( χ2=8.31, P=0.004), group cooperation ( χ2=21.10, P<0.001), assessment form ( χ2 =7.92, P=0.005), improvement of the writing ability of scientific research papers ( χ2 =17.56, P<0.001), improvement of practical skills ( χ2=11.70, P=0.001), logical thinking, language organization and expression ability ( χ2=10.33, P=0.001). They considered the opening experiment was helpful to cultivate innovative thinking and ability, but it had limited effect on the cultivation of employment advantages. And the students considered the opening experiments of setting up professional courses was sufficient and necessary. Conclusion:Carrying out opening experiments for students majoring in preventive medicine is helpful to improve students' professional quality and cultivate their practical ability and scientific research ability.

A metaheuristics-based automatic planning method for intensity-modulated radiation therapy / 中华放射医学与防护杂志

Objective:To establish a metaheuristics-based automatic radiotherapy treatment planning method (ATP-STAR) and verify its effectiveness.Methods:The main process of the ATP-STAR method was as follows. First, the optimization parameters were vectorized for encoding and corrected using Gaussian convolution. Then, the candidate optimization parameter vector set was selected through simulated annealing. Finally, the optimal combination of optimization parameters was determined by combining the field fluence optimization to achieve automatic trial-and-error. Twenty cases with large individual differences in tumors were selected for testing. Clinical physicists with more than five years of experience were invited to perform manual planning. Both the manual and ATP-STAR plans were made utilizing the matRad open source software for radiation treatment planning, with the fields and prescribed doses consistent with those of the clinical treatment plans. The dosimetric differences of target volumes and organs at risk between the ATP-STAR and manual plans for different diseases were analyzed.Results:For the target volumes, the ATP-STAR plans showed superior homogeneity compared with the manual plans (brain tumors: z = 2.28, P = 0.022; lung cancers: z = 2.29, P = 0.022; liver cancers: z = 2.11, P = 0.035). The conformability of the ATP-STAR plans was comparable to that of the manual plans for brain tumors and liver cancer and was slightly lower than that of the manual plans for lung cancer ( z = 2.29, P = 0.022). The comparison result of doses to organs at risk (OARs) between the manual plans and STAR plans were as follows. For OARs of brain tumors, the ATP-STAR plans decreased the mean left lens Dmean from 2.19 Gy to 1.76 Gy ( z = 2.28, P = 0.022), decreased left optic nerve Dmean from 11.36 Gy to 10.22 Gy ( z = 2.28, P = 0.022), decreased right optic nerve Dmax from 32.92 Gy to 29.97 Gy ( z = 2.10, P = 0.036), and decreased pituitary Dmax from 39.53 Gy to 35.21 Gy ( z = 2.29, P = 0.022). For OARs of lung cancer, the ATP-STAR plans decreased the mean spinal cord Dmax from 38.00 Gy to 31.17 Gy ( z = 2.12, P = 0.034), decreased the bilateral lungs Dmean from 8.51 Gy to 8.07 Gy ( z = 2.29, P = 0.022), and decreased cardiac Dmean from 3.21 Gy to 2.69 Gy ( z =2.29, P = 0.022). For OARs of liver cancer, the ATP-STAR plans decreased spinal cord Dmax from 18.19 Gy to 14.76 Gy ( z = 2.11, P = 0.035), decreased liver Dmean from 15.61 Gy to 14.45 Gy ( z = 2.11, P = 0.035), and decreased kidneys Dmean from 4.76 Gy to 4.04 Gy ( z = 2.10, P = 0.036). Conclusions:The proposed ATP-STAR method relies little on the experience of manual planning and thus is easy to be widely applied. This method is expected to improve the quality and consistency of IMRT plans and save clinical labor and time costs.

A dosimetric study on off-target isocenter plans for stereotactic body radiotherapy of lung cancer / 中华放射医学与防护杂志

Objective:To investigate the effects of off-target isocenter plans with different off-target distances on the plan quality and delivery accuracy of stereotactic body radiotherapy (SBRT) for lung cancer, aiming to provide a reference for the clinical plan design of SBRT for lung cancer.Methods:For 10 lung cancer patients treated with SBRT, isocenter reference plans were designed by setting the plan isocenters at the mass centers of tumors and 60 off-target isocenter plans by setting the isocenters at distances of 1, 3, 5, 8, and 10 cm from the mass centers of tumors. The dosimetric differences between the off-target isocenter plans and the reference plans. Subsequently was analyzed, under different positional errors (0-5 mm). The gamma pass rates (GPRs) of these plans were measured using the Octavius 4D high-resolution dose verification system, and 240 verifications of these plans were completed. The robustness of the delivery accuracy of the reference plans and off-target isocenter plans were analyzed under different positional errors.Results:The off-target isocenter plans yielded slightly worse dose gradient indices than the isocenter reference plans, but there was no statistically significant differences. With an increase in the off-target distance, the mean lung dose (MLD), V20 of normal lungs, as well as the Dmax of bronchi, showed slight upward trends. Compared with the isocenter reference plans, the MLD of the off-target isocenter plans increased by 0.8%, 0.8%, and 1.9% at off-target distances of 1, 3, and 10 cm, respectively, with statistically significant differences ( z = -2.34 to -1.99, P < 0.05), and the V20 of the off-target isocenter plans increased by 2.0%, 2.5%, and 3.7% at off-target distances of 1, 5, and 10 cm, respectively, with statistically significant differences ( z =-2.11 to -1.99, P < 0.05). In the case of a positional error of up to 5 mm, the GPRs of plans with off-target distances of 5 cm and above decreased by more than 1.0% on average and up to a maximum of 3.5%, showing statistically significant differences ( z = 2.13-2.75, P < 0.05). Conclusions:Compared to the reference plans, the off-target isocenter plans showed slightly lower dosimetric quality and less robust delivery accuracy under different positional errors. Therefore, it is necessary to avoid the plans and treatment with too large off-target distances (≥ 5 cm) as far as possible for SBRT of lung cancer.

Effect of dwell time deviation constraint on the three-dimensional brachytherapy plans for cervical cancer / 中华放射肿瘤学杂志

Objective:To investigate the effect of dwell time deviation constraint of inverse optimization on the quality and position error robustness of three-dimensional (3D) brachytherapy plans for cervical cancer.Methods:A total of 20 patients with cervical cancer receiving 3D brachytherapy treatment in Xiangya Hospital Central South University from August 2020 to August 2021 were retrospectively selected. All plans were designed using the Eclipse treatment planning system, and the dwell time deviation constraint parameter smooth value in the system were set to 0.00, 0.25, 0.50, 0.75, and 1.00, respectively. An inverse dose volume optimization algorithm was used to generate plans with various smooth values, and the optimization conditions were the same as the original clinical plans. Key dosimetric metrics and total dwell time differences were comparatively analyzed. The applicators were intentionally subjected to position errors (0.2-1.0 cm) in 6 directions (left-right, anterior-posterior, head-foot), and the effect of various smooth values on plan quality and robustness was assessed. There were 133 plans per case and 2 660 plans for 20 patients. The results were statistically analyzed using the Wilcoxon signed-rank nonparametric test.Results:As the smooth value was increased, the modulation factor was gradually decreased and the D 2 cm3 of the bladder and rectum was increased. Plans with smooth values of 0.25, 0.50, 0.75, 1.00 had modulation factors of 0.72±0.09, 0.63±0.08, 0.55±0.08, 0.51±0.06, respectively, lower than 0.75±0.05 of the plan with the smooth value of 0.00, and all differences were statistically significant ( P=0.004, 0.002, 0.002, 0.002). The bladder D 2 cm3 of plans with smooth values of 0.50, 0.75, 1.00 were (475.4±41.0) cGy, (483.7±46.2) cGy, and (489.0±46.8) cGy, respectively, higher than (469.8±41.8) cGy of the plan with the smooth value of 0.00, with statistically significant differences (all P=0.002). The rectum D 2 cm3 of plans with smooth values of 0.50 and 0.75 plans were (413.2±93.3) cGy and (418.6±96.4) cGy, both higher than (410.2±91.5) cGy of the plan with the smooth value of 0.00, with statistically significant differences ( P=0.006, 0.010). When positional errors were introduced, the high risk clinical target volume (HR-CTV) D 90% was close for different smooth plans at most positional errors, and the differences were not statistically significant. The organs at risk D 2 cm3 of plans with the smooth value of 0.00 was lower than those of plans with other smooth values, and for the bladder and rectum, the differences were statistically significant at most positional errors (all P<0.01). Conclusions:The dwell time deviation constraint parameter exerts significant effect on the plan quality, and the smaller the value of the constraint parameter, the higher quality of the plan. The dwell time deviation constraint parameter has slight impact on the positional error robustness of dosimetric indices of targets and key organs at risk.

A diabetic foot classification model based on radiomics features of fundus photographs / 中华内分泌代谢杂志

Objective:To construct a diabetic foot classification prediction model based on radiomics features of fundus photographs.Methods:A total of 2 035 fundus photographs of patients with type 2 diabetes diagnosed at Nanfang Hospital between December 2011 and December 2018 were retrospectively collected [282 photographs from patients with diabetic foot(DF), and 1 753 from patients with diabetes mellitus(DM)]. All fundus photographs were randomly divided into a training set(1 424 photos) and a test set(611 photos) using a computer generated random number at 7∶3. After pre-processing the fundus photographs, a total of 4 128 texture features based on the gray matrix were extracted by the Radiomic toolkit, and 11 339 other features were extracted using the ToolboxDESC toolkit. The LASSO algorithm was used to select the 30 features most relevant to DF, and then the Bootstrap + 0.632 self-sampling method was used to further select the 7 best combinations. Logistic regression analysis was used to obtain the regression coefficients and establish the final diabetic foot classification prediction model. ROC curve was drawn, and AUC, sensitivity, specificity, and accuracy of the training and test sets were calculated to verify its prediction performance. Results:We screened 7 fundus radiomics markers for diabetic foot patients, and based on this established a DF/DM classification prediction model. The AUC, sensitivity, specificity, and accuracy of the model were 0.958 6, 0.984 0, 0.920 0, and 0.928 0 in the training set, and 0.927 1, 0.988 9, 0.881 0, and 0.896 9 in the test set, respectively.Conclusion:In this study, seven DF fundus markers were screened using radiomics technology. Based on this, a highly accurate and easy-to-use DF/DM classification model was constructed. This technology has the potential to increase the efficiency of DF screening programs.

Effects of exosomes derived from cardiac fibroblasts treated with hypothermic hypoxia-reoxygenation on ventricular electrical conduction during hypothermic cardiac ischemia-reperfusion in rats / 中华麻醉学杂志

Objective:To evaluate the effects of exosomes derived from cardiac fibroblasts treated with hypothermic hypoxia-reoxygenation on ventricular electrical conduction during hypothermic cardiac ischemia-reperfusion (I/R) in rats.Methods:SPF neonatal Sprague-Dawley rats of either sex, aged 1-2 days, were used, and primary cardiac fibroblasts were extracted by differential adhesion method. The cells were passaged for 2-4 generations. When the cell density reached 60%-70%, the cells were transferred and exposed to 95% N 2 + 5% CO 2 for 1 h at 4 ℃, and then exposed to 95% air + 5% CO 2 for 24-48 h at 37 ℃, and then exosomes were extracted. Twenty-four SPF healthy adult male Sprague-Dawley rats, aged 2-3 months, weighing 280-360 g, were divided into 3 groups ( n=8 each) according to the random number table method: control group (group C), hypothermic cardiac IR group (I/R group) and exosome + hypothermic cardiac IR group (Exo-IR group). At 48 h before equilibrium perfusion, 1.5 ml (200 μg) of exosomes secreted by cardiac fibroblasts treated with hypothermic hypoxia-reoxygenation was injected into the tail vein in Exo-IR group, and PBS 1.5 ml was injected into the tail vein in C group and IR group each. Group C received 110 min equilibration perfusion. After 20 min of equilibration, the perfusion was suspended for 60 min (global ischemia) followed by 30 min of reperfusion in IR and Exo-IR groups. Microelectrode arrays were applied at 20 min of equilibrium perfusion and 15 and 30 min of reperfusion to obtain myocardial conduction velocity (CV), absolute conduction inhomogeneity (P 5-95) and inhomogeneity index (P 5-95/P 50) on the left ventricular surface of isolated rat hearts. Results:Compared with group C, the CV was significantly decreased at 15 and 30 min of reperfusion, and P 5-95 and P 5-95/P 50 were increased in IR and Exo-IR groups ( P<0.05). Compared with IR group, CV was significantly increased at 15 and 30 min of reperfusion, and P 5-95 and P 5-95/P 50 were decreased in Exo-IR group ( P<0.05). Conclusions:Exosomes derived from cardiac fibroblasts treated with hypothermic hypoxia-reoxygenation can improve ventricular electrical conduction during hypothermic cardiac I/R in rats.

Research progress of intelligent reversible drug delivery system / 药学学报

In the research on cancer theranostics, most environment-sensitive drug delivery systems can only achieve unidirectional and irreversible responsive changes under pathological conditions, thereby improving the targeting effect and drug release performance of the delivery system. However, such irreversible changes pose potential safety hazards when the dynamically distributed delivery system returns to the blood circulation or transports to the normal physiological environment. Intelligent reversible drug delivery systems can respond to normal physiological and pathological microenvironments to achieve bidirectional and reversible structural changes. This feature will help to precisely control the drug release of the delivery system, prolong the blood circulation time, improve the targeting efficiency, and avoid the potential safety hazards of the irreversible drug delivery system. In this review, we describe the research progress of intelligent reversible drug delivery system from two main aspects: controlled drug release and prolonged blood circulation time/enhanced cellular internalization of drug.

Physiological pharmacokinetic model of children and its application of modeling software / 药学学报

Developmental changes in children can affect drug disposition and clinical effects. A physiologically-based pharmacokinetic (PBPK) model is a mathematical model that can be used to predict blood drug concentrations in children and gain insight into age-dependent physiological differences in drug disposition impact. Pediatric PBPK (P-PBPK) models have attracted attention over the past decade. With the concerted efforts of academia, pharmaceutical companies, and regulatory agencies, there are more and more examples of pediatric clinical studies using PBPK models. Nevertheless, the number of P-PBPK models and their predictive performance still lag behind adult models. By referring to the literature, we study the process of children adapting to adult absorption, distribution, metabolism, and excretion (ADME) parameters and analyze the general principles of P-PBPK model establishment. In addition, we summarize the functions and application examples of commonly used P-PBPK modeling software to provide a basis for the rational application of modeling software.

Engineering and application of Komagataella phaffii as a cell factory / 生物工程学报

Nowadays, engineered Komagataella phaffii plays an important role in the biosynthesis of small molecule metabolites and protein products, showing great potential and value in industrial productions. With the development and application of new editing tools such as CRISPR/Cas9, it has become possible to engineer K. phaffii into a cell factory with high polygenic efficiency. Here, the genetic manipulation techniques and objectives for engineering K. phaffii are first summarized. Secondly, the applications of engineered K. phaffii as a cell factory are introduced. Meanwhile, the advantages as well as disadvantages of using engineered K. phaffii as a cell factory are discussed and future engineering directions are prospected. This review aims to provide a reference for further engineering K. phaffii cell factory, which is supposed to facilitate its application in bioindustry.

Sea-buckthorn slows down-regulation of CYP 2C in mice with liver injury by BCG-induced via PXR/NF-κB pathway / 中国药理学通报

Aim To explore whether sea-buckthorn slows down-regulation of hepatic cytochrome P450 2C(CYP 2C)in mice with liver injury by BCG vaccine(BCG)-induced via PXR/NF-κB pathway.Methods The mouse model of liver injury was induced by a single tail vein injection of BCG 125 mg·kg-1 for hepatitis B research,and the mice were randomly di-vided into control group,BCG group,BCG+sea-buckthorn granules(SG)group(gavage 50,100,200 mg·kg-1,twice a day),BCG+PCN group(intraper-itoneal injection 100 mg·kg-1,once a day).The levels of serum transaminase and TNF-α and IL-1β in liver tissue were detected by ELISA.The nuclear pro-tein expression NF-κB p65 and the total protein expres-sion of pregnane X receptor(PXR),CYP2C in liver were detected by Western blot.Liver pathological changes were observed by HE staining.Results Sea-buckthorn inhibited overexpression of TNF-α,IL-1βand NF-κB p65,alleviated the down-regulation of CYP2C and PXR protein expression,and improved liv-er pathology and serum transaminase in a dose-depend-ent manner.After intervention with PCN,a mouse specific agonist of PXR,it was similar to the high dose group of SG.Conclusion Sea-buckthorn slows down-regulation of CYP2C in mice with liver injury by BCG-induced via PXR/NF-κB pathway.

Noise reduction in low-dose computed tomography with noise equivalent image and deep learning / 中华放射医学与防护杂志

Objective:To investigate the method of simulating low-dose CT (LDCT) images using routine dose level scanning mode to generate LDCT images with correspondence to the routine dose CT (RDCT) images in the training sets for deep learning model, which would be used for LDCT noise reduction.Methods:The CT images reconstructed by different algorithms in Philips CT Big Core had different noise levels, where the noise was larger with iDose 4 algorithm and lower with IMR(knowledge-based iterative model reconstruction)algorithm. A new method of replacing LDCT image with noise equivalent reconstructed image was proposed. The uniform module of CTP712 was scanned with the exposure of 250 mAs for RDCT, 35 mAs for LDCT. The images were reconstructed using IMR algorithm for LDCT images and iDose 4 algorithm at multiple noise reduction levels for RDCT images, respectively. The noise distribution of each image set was analyzed to find the noise equivalent images of LDCT. Then, RDCT images, those selected images were used for training cycle-consistent adversarial networks (CycleGAN)model, and the noise reduction ability of the proposed method on real LDCT images of phantom was tested. Results:The RDCT images generated with iDose 4 level 1 could substitute the LDCT images reconstructed with IMR algorithm. The radiation dose was reduced by 86% in low dose scanning. Using CycleGAN model, the noise reduction degree was 45% for uniform module, and 50%, 13%, 7% for CIRS-SBRT 038 phantom in the specific regions of brain, spinal cord, bone, respectively. Conclusions:Equivalent noise level reconstructed images could potentially serve as the alternative of LDCT images for deep learning network training to avoid additional radiation dose. The generated CT images had substantially reduced noise relative to that of LDCT.

Preliminary application of MR-Linac in breast cancer radiotherapy in a single academic center / 中华放射肿瘤学杂志

Objective:To describe a prospective study of pre-operative tumor-bed boost performed at the 1.5 T MR-Linac in combination with adjuvant whole breast irradiation, and a first case, with an accentuation on clinical feasibility and safety.Methods:A phase II, single arm study recruiting early stage patients follows a paradigm that first boosts the tumor bed and then undergoes breast conservative surgery in 2 weeks, and last irradiates the whole breast in 6 weeks. The primary endpoint is ≥ grade 2 acute breast toxicity. A 43 years old patient affected by a breast carcinoma, not special type of the right-sided lateral quadrant, staged cT 2N 0M 0, was planned and treated. The dose, 8 Gy for one time, was calculated by Monaco on CT simulation images. Both the air electron stream effect (ESE) and the electron return effect (ERE) at the presence of 1.5 T magnetic field were evaluated. During the pre-treatment evaluation, we carried out adaptation-to-position adjustment. Results:The normal organ dosimetry is within toleration. The Dmax to the skin, the chin and the right upper arm was 8.44 Gy, 28.5 cGy and 17.8 cGy, respectively. There was no increased toxicity from ERE and ESE, and the treatment was well tolerated without > grade 1 acute toxicity. The patient received breast conservative surgery on day 7 without delayed wound healing.Conclusions:This is the first case successfully treated within a clinical trial by pre-operative tumor-bed boost under 1.5 T MR-Linac in our institution. More participants are needed to validate and optimize the paradigm.