Objective To investigate the effects of alpha lipoic acid on patients with diabetic retinopathy (DR),explore the possible mechanisms,and provide experimental evidence for the treatment of DR with lipoic acid.Methods Totally 75 DR patients were randomly divided into control group and treatment group.Patients in control group received the standard hypoglycemic treatment,antihypertensive therapy,and other comprehensive treatment.Patients from the treatment group were treated with alpha lipoic acid 600 mg + 250 ml 0.9％ sodium chloride injection additionally,avoiding light intravenous therapy,for a total of 4 weeks.Before and after treatment,fundus fluorescein angiography and visual inspection were detected in two groups.In addition,serum level of asymmetric dimethylarginine (ADMA) were detected with high performance liquid chromatography,serum lipid peroxidation product malondialdehyde (MDA) content and superoxide dismutase (SOD) activity were detected to reflect the in vivo oxidative stress before and after treatment in two groups.Results Compared to the control group,visual acuity was improved significantly (P ＜ 0.05),and total efficiency of ocular lesions-improved was increased significantly (84.21％ vs 40.54％,x2 =15.28,P ＜ 0.01).Serum levels of endogenous inhibitor of nitric oxide synthase ADMA [(0.32 ±0.13) μmol/L vs (0.51 ± 0.26) μmol/L,P ＜ 0.05] and MDA [(3.22 ± 0.90) nmol/L vs (5.13 ± 0.42) nmol/ml,P ＜ 0.05] were significantly decreased,while SOD levels [(72.68 ± 1.31) U/ml vs (53.16 ± 1.54) U/ml,P ＜0.05] were significantly increased in DR patients after alpha lipoic acid treatment.Conclusions Alpha lipoic acid had some therapeutic effects for DR patients,which mainly lied in the improvement of visual acuity and eye disease,might be related to the decrease of oxidative stress and serum level of endogenous nitric oxide synthase (NOS) inhibitor ADMA.

Objective To investigate the changes of visual acuity,fundus changes,and serum vitamin D concentration in diabetic retinopathy patients treated with metformin,and to evaluate its clinical efficacy.Methods Totally 80 cases (160 eyes) patients with background diabetic retinopathy were included in the study,and were divided into observation group (metformin + Pancreatic Kininogenase Enteric-coated Tablets) and control group (Pancreatic Kininogenase Enteric-coated Tablets) according to the different treatment methods used for 3 months.Fundus fluorescein angiography was used to evaluate the improvement of the fundus lesions.The serum levels of vitamin D were measured with electrochemiluminescence immunoassay (ECLIA).Results After 3 months of treatment,serum vitamin D concentration of the observation group increased,and the differences were statistically significant (P ＜ 0.05) when compared to before treatment.However,3 months after treatment,serum vitamin D levels of the control group increased slightly,but the difference was not statistically significant (P ＞ 0.05).The total effective rate of fundus improvement in the observation group and the control group was 70％ and 55％,respectively.There was significant difference between the two groups in the improvement of fundus (P ＜ O.05).Conclusions Metformin has an adjunctive effect on background diabetic retinopathy,and the increase of serum vitamin D may be one of the mechanisms of metformin in improving diabetic retinopathy.

Objective :To explore influence of CYP2C19 gene polymorphism on clopidogrel resistance after percutane‐ous coronary intervention (PCI) in patients with coronary heart disease (CHD).Methods :A total of 100 CHD pa‐tients ,who were treated and received PCI in our hospital ,were selected .There were 24 cases with clopidogrel re‐sistance (CR ,CR group) and 76 cases without CR (NCR ,NCR group).According to CYP2C19 genotype ,patients were divided into rapid metabolism CYP2C19*1／*1 (n＝49) ,medium metabolism CYP2C19*1／*2 (n＝28) and*1／*3 (n＝11) ,and slow metabolism CYP2C19*2／*2 (n＝9) and *2／*3 (n＝3).Relationship among differ‐ent genotypes ,CR ,maximum platelet aggregation rate (MPA) and incidence of major adverse cardiovascular events (MACE) were analyzed .Results :With rapid metabolism CYP2C19*1／*1 as the base ,there was significant rise in CR risk in medium metabolism (CYP2C19*1／*2 and *1／*3 ,OR＝4. 16 ,5. 03 , P＜0.05 both) and slow metab‐olism (CYP2C19*2／*2 and *2／*3 ,OR＝7.04 ,17. 6 , P＜0.01 both ) ,medium metabolism increased by 4. 16 and 5. 03 times respectively ,while slow metabolism increased by 7. 04 and 17. 60 times respectively .Compared with rapid metabolism genotype ,there were significant rise in MPA and incidence rate of MACE in medium and slow me‐tabolism genotypes , P＜0.05 or ＜0. 01 ;incidence rate of MACE in CR group was significantly higher than that of NCR group (20. 8% vs.5. 3%, P＝0.02).Conclusion : CYP2C19 gene polymorphism possesses certain influence on CR after PCI in CHD patients .Those with medium or slow metabolism genotypes are more likely to suffer from CR ,higher MPA and incidence rate of MACE .

Objective: To explore the influences of comprehensive nursing intervention on the caregivers of severely burned children. Methods: Eighty severely burned children, admitted to our department from November 2016 to November 2017 and conforming to the study criteria, were included in this study. They were divided into comprehensive group and control group according to the random number table, with 40 children in each group. One caregiver for each child was included in the same group. Children and caregivers in control group had routine nursing care while children and caregivers in comprehensive group had comprehensive nursing care on the base of routine nursing care, including comprehensive psychological nursing of children and caregivers, guidance of rehabilitation for caregivers throughout the entire recovery process, individualized propaganda and education for caregivers on account of disease of children, perfecting social support system, sustained attention of children during follow-up. Anxiety self-rating scale and social support rating scale were used to assess the levels of anxiety and social support of caregivers of children in the two groups at the time of admission (before intervention) and the second month after discharge (the third time follow-up, after intervention). On the day of discharge, the nursing service satisfaction questionnaire of our department was used to evaluate the nursing service satisfaction of caregivers of children. Data were processed with chi-square test and independent sample t test. Results: (1) Before intervention, the anxiety and social support scores of caregivers of children in control group were respectively (64.5±3.8) and (40.4±2.5) points, similar to (63.5±4.9) and (40.5±2.6) points in comprehensive group (t=0.988, 0.177, P>0.05). After intervention, the anxiety score [(47.2±1.9) points] of caregivers of children in comprehensive group was significantly lower than that of control group [(57.6±4.3) points, t=13.917, P<0.01], and the social support score [(45.3±1.9) points] was significantly higher than (35.9±2.1) points in control group (t=-21.282, P<0.01). After intervention, scores of objective support, subjective support, and social support utilization in the social support evaluation rating of caregivers of children in comprehensive group were significantly higher than those in control group (t=12.678, -11.079, -10.031, P<0.01). (2) At the time of discharge, scores of clinical care, propaganda and education content and form in the nursing service satisfaction questionnaire of caregivers of children in comprehensive group were significantly higher than those of control group (t=-14.757, -15.627, -33.221, P<0.01). Conclusions Comprehensive nursing intervention method can effectively reduce the anxiety of the caregivers of severely burned children, help them to make better use of social support system, and improve the satisfaction of caregivers in nursing services.

The high neurogenic potential of dental and oral-derived stem cells due to their embryonic neural crest origin, coupled with their ready accessibility and easy isolation from clinical waste, make these ideal cell sources for neuroregeneration therapy. Nevertheless, these cells also have high propensity to differentiate into the osteo-odontogenic lineage. One strategy to enhance neurogenesis of these cells may be to recapitulate the natural physiological electrical microenvironment of neural tissues via electroactive or electroconductive tissue engineering scaffolds. Nevertheless, to date, there had been hardly any such studies on these cells. Most relevant scientific information comes from neurogenesis of other mesenchymal stem/stromal cell lineages (particularly bone marrow and adipose tissue) cultured on electroactive and electroconductive scaffolds, which will therefore be the focus of this review. Although there are larger number of similar studies on neural cell lines (i.e. PC12), neural stem/progenitor cells, and pluripotent stem cells, the scientific data from such studies are much less relevant and less translatable to dental and oral-derived stem cells, which are of the mesenchymal lineage. Much extrapolation work is needed to validate that electroactive and electroconductive scaffolds can indeed promote neurogenesis of dental and oral-derived stem cells, which would thus facilitate clinical applications in neuroregeneration therapy.
Cell Differentiation ; Mesenchymal Stem Cells/metabolism* ; Neural Stem Cells/metabolism* ; Neurogenesis ; Tissue Scaffolds

ObjectiveTo investigate the effect of linalool against acute liver injury induced by aflatoxin B₁（AFB₁） in rats and explore its protective mechanism. MethodTwenty male SPF SD rats were randomly divided into three groups： Control （n=6）， AFB₁ （n=7）， and linalool （n=7） groups. Linalool solution （200 mg·kg^-1） was administered preventatively for 14 days， while the control and AFB₁ groups intragastrically received an equivalent volume of double distilled water. After preventative administration of linalool， AFB₁ solution （1 mg·kg^-1， dissolved in saline） was intraperitoneally injected for two consecutive days to induce acute liver injury in rats. Samples were collected and processed 14 days after model establishment. Pathological changes in liver tissue of rats were observed using Hematoxylin-eosin（HE） staining and Masson staining. Biochemical detection was performed to measure the levels of alanine transaminase（ALT）， aspartate transaminase（AST）， γ-glutamyl transferase（GGT）， lactate dehydrogenase（LDH）， alkaline phosphatase（ALP）， total bilirubin（TBil）， direct bilirubin（DBil）， indirect bilirubin（IBil）， malondialdehyde（MDA）， superoxidedismutase（SOD）， catalase（CAT） ， glutathione（GSH）， Fe³⁺， and Fe²⁺ in the liver tissue. Western blot was adopted to assess protein expression levels of nuclear factor-erythroid 2-related factor 2（Nrf2） and heme oxygenase-1（HO-1）. Molecular docking was performed to verify the binding between linalool and key proteins of the Nrf2/HO-1 signaling pathway. Molecular dynamics techniques were used to confirm the stability and affinity of linalool binding with key proteins of the Nrf2/HO-1 signaling pathway. ResultPathological results showed that compared to that in the AFB₁ group， the liver structure in the linalool group tended to be normal， with a significant decrease in blue collagen fibers. The linalool group exhibited significantly reduced levels of ALT， AST， GGT， LDH， ALP， TBil， DBil， and IBil （P<0.01）， Fe³⁺ and Fe²⁺ content， and oxidative stress marker MDA （P<0.01）. The levels of antioxidants SOD， CAT， and GSH significantly increased （P<0.01）. Molecular docking showed a molecular docking energy between linalool and Nrf2 and HO-1 targets of -5.495 6 and -5.199 4 kcal·mol^-1（1 cal≈4.186 J）， respectively. Molecular dynamics results indicated strong affinity in the binding of linalool with Nrf2 and HO-1. Western blot revealed a significant increase in Nrf2 protein expression （P<0.05） and a decrease in HO-1 protein expression （P<0.01） in the linalool group. ConclusionLinalool may protect against AFB₁-induced acute liver injury by modulating the Nrf2/HO-1 ferroptosis signaling pathway to inhibit liver cell ferroptosis and regulate hepatic oxidative stress levels.

Objective: To investigate the mechanism of Yishen Tongluo Formula in ameliorating renal pyroptosis in diabetic nephropathy mice by regulating the toll-like receptor 4 (TLR4)/myeloid differentiation factor 88 (MyD88)/nuclear factor-κB (NF-κB) signaling pathway. Methods: Sixty C57BL/6 male mice were randomly divided into control (10 mice) and intervention groups (50 mice) using random number table method. The diabetes nephropathy model was established by intraperitoneally injecting streptozotocin(50 mg/kg). After modeling, the intervention group was further divided into model, semaglutide (40 μg/kg), and high-, medium-, and low-dose Yishen Tongluo Formula groups (15.6, 7.8, and 3.9 g/kg, respectively) using random number table method. The high-, medium-, and low-dose Yishen Tongluo Formula groups were administered corresponding doses of medication by gavage, the semaglutide group received a subcutaneous injection of semaglutide injection, and the control group and model groups were administered distilled water by gavage for 12 consecutive weeks. Random blood glucose levels of mice in each group were monitored, and the 24-h urinary protein content was measured using biochemical method every 4 weeks; after treatment, the serum creatinine and urea nitrogen levels were measured using biochemical method. The weight of the kidneys was measured, and the renal index was calculated. Hematoxylin and eosin, periodic acid-Schiff, periodic Schiff-methenamine, and Masson staining were used to observe the pathological changes in renal tissue. An enzyme-linked immunosorbent assay was used to detect urinary β2-microglobulin (β2-MG), neutrophil gelatinase-associated lipocalin (NGAL), and kidney injury molecule-1 (KIM-1) levels. Western blotting and real-time fluorescence PCR were used to detect the relative protein and mRNA expression levels of nucleotide-binding domain leucine-rich repeat and pyrin domain-containing receptor 3 (NLRP3), Caspase-1, gasdermin D (GSDMD), interleukin-1β (IL-1β), and interleukin-18 (IL-18) in renal tissue. Immunohistochemistry was used to detect the proportion of protein staining area of the TLR4, MyD88, and NF-κB in renal tissue. Results: Compared with the control group, the random blood glucose, 24-h urinary protein, serum creatinine, urea nitrogen, and renal index of the model group increased, and the urine β2-MG, NGAL, and KIM-1 levels increased. The relative protein and mRNA expression levels of NLRP3, Caspase-1, GSDMD, IL-1β, and IL-18 in renal tissue increased, and the proportion of TLR4, MyD88, and NF-κB protein positive staining areas increased (P<0.05). Pathological changes such as glomerular hypertrophy were observed in the renal tissue of the model group. Compared with the model group, the Yishen Tongluo Formula high-dose group showed a decrease in random blood glucose after 12 weeks of treatment (P<0.05). The Yishen Tongluo Formula high- and medium-dose groups showed a decrease in 24-h urinary protein, creatinine, urea nitrogen, and renal index, as well as decreased β2-MG, NGAL, and KIM-1 levels. NLRP3, Caspase-1, GSDMD, IL-1 β, and IL-18 relative protein and mRNA expression levels were also reduced, and the proportion of TLR4, MyD88, and NF-κB protein positive staining areas was reduced (P<0.05). Pathological damage to renal tissue was ameliorated. Conclusion Yishen Tongluo Formula may exert protective renal effects by inhibiting renal pyroptosis and alleviating tubular interstitial injury in diabetic nephropathy mice by regulating the TLR4/MyD88/NF-κB signaling pathway.

At present, there are many monitoring devices for vital signs parameters for clinical selection, but urine monitoring has not received enough attention. The traditional manual visual measurement, intermittent measurement of urine pH value, and other methods are still in use, so the authors designed a multifunctional urine bag. The urine bag can set up an alarm system per unit time according to patient′s age and condition as well as set up urine pH value detection area in hard plastic measuring bottle. This device can not only accurately monitor urine volume per unit time, but also hopefully realize the alarm automation of abnormal urine volume per unit time, as well as real-time dynamic monitoring of urine pH value. It is helpful for medical staff to make accurate judgment on patients′ condition changes, to guide the formulation and modification of clinical treatment plans, and to reduce the workload of clinical nursing staff to a certain extent.

Oral diseases concern almost every individual and are a serious health risk to the popula-tion.The restorative treatment of tooth and jaw defects is an important means to achieve oral function and support the appearance of the contour.Based on the principle of"learning from the nature",Deng Xu-liang's group of Peking University School and Hospital of Stomatology has proposed a new concept of"microstructural biomimetic design and tissue adaptation of tooth/jaw materials"to address the worldwide problems of difficulty in treating dentine hypersensitivity,poor prognosis of restoration of tooth defects,and vertical bone augmentation of alveolar bone after tooth loss.The group has broken through the bottle-neck of multi-stage biomimetic technology from the design of microscopic features to the enhancement of macroscopic effects,and invented key technologies such as crystalline/amorphous multi-level assembly,ion-transportation blocking,and multi-physical properties of the micro-environment reconstruction,etc.The group also pioneered the cationic-hydrogel desensitizer,digital stump and core integrated restora-tions,and developed new crown and bridge restorative materials,gradient functionalisation guided tissue regeneration membrane,and electrically responsive alveolar bone augmentation restorative membranes,etc.These products have established new clinical strategies for tooth/jaw defect repair and achieved inno-vative results.In conclusion,the research results of our group have strongly supported the theoretical im-provement of stomatology,developed the technical system of oral hard tissue restoration,innovated the clinical treatment strategy,and led the progress of the stomatology industry.

ObjectiveTo investigate the effect and mechanism of Yishen Tongluo prescription in protecting mice from oxidative stress injury in diabetic kidney disease （DKD） via the nuclear factor erythroid 2-related factor 2 （Nrf2）/heme oxygenase-1 （HO-1）/NAD（P）H quinone oxidoreductase 1 （NQO1） signaling pathway. MethodsSpecific pathogen-free （SPF） male C57BL/6 mice were assigned into a control group （n=10） and a modeling group （n=50）. The DKD model was established by intraperitoneal injection of streptozotocin. The mice in the modeling group were randomized into a model group， a semaglutide （40 μg·kg^-1） group， and high-， medium-， and low-dose （18.2， 9.1， 4.55 g·kg^-1， respectively） Yishen Tongluo prescription groups， with 10 mice in each group. The treatment lasted for 12 weeks. Blood glucose and 24-h urine protein levels were measured， and the kidney index （KI） was calculated. Serum levels of creatinine （SCr）， blood urea nitrogen （BUN）， alanine aminotransferase （ALT）， and aspartate aminotransferase （AST） were assessed. The pathological changes in the renal tissue were evaluated by hematoxylin-eosin， periodic acid-Schiff， periodic acid-silver methenamine， and Masson’s trichrome staining. Enzyme-linked immunosorbent assay kits were used to measure the levels of β2-microglobulin （β2-MG）， neutrophil gelatinase-associated lipocalin （NGAL）， kidney injury molecule-1 （KIM-1）， liver fatty acid-binding protein （L-FABP）， nitric oxide synthase （NOS）， glutathione （GSH）， total antioxidant capacity （T-AOC）， and 8-hydroxy-2'-deoxyguanosine （8-OHdG）. Immunohistochemical staining was performed to examine the expression of Kelch-like ECH-associated protein 1 （Keap1） and malondialdehyde （MDA）. Real-time fluorescence quantitative polymerase chain reaction (Real-time PCR） and Western blot were employed to determine the mRNA and protein levels， respectively， of factors in the Nrf2/HO-1/NQO1 signaling pathway. ResultsCompared with the control group， the DKD model group showed rises in blood glucose， 24-h urine protein， KI， SCr， BUN， and ALT levels， along with glomerular hypertrophy， renal tubular dilation， thickened basement membrane， mesangial expansion， and collagen deposition. Additionally， the model group showed elevated levels of β2-MG， NGAL， KIM-1， L-FABP， NOS， and 8-OHdG， lowered levels of GSH and T-AOC， up-regulated expression of MDA and Keap1， and down-regulated expression of Nrf2， HO-1， NQO1， and glutamate-cysteine ligase catalytic subunit （GCLC） （P<0.05）. Compared with the model group， the semaglutide group and the medium- and high-dose Yishen Tongluo prescription groups showed reductions in blood glucose， 24-h urine protein， KI， SCr， BUN， and ALT levels， along with alleviated pathological injuries in the renal tissue. In addition， the three groups showed lowered levels of β2-MG， NGAL， KIM-1， L-FABP， NOS， and 8-OHdG， elevated levels of GSH and T-AOC， down-regulated expression of MDA and Keap1， and up-regulated expression of Nrf2， HO-1， NQO1， and GCLC （P<0.05）. ConclusionYishen Tongluo prescription exerts renoprotective effects in the mouse model of DKD by modulating the Nrf2/HO-1/NQO1 signaling pathway， mitigating oxidative stress， and reducing renal tubular injuries.