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.

Circadian rhythms are self-sustaining oscillations within biological systems that play key roles in a diverse multitude of physiological processes.The circadian clock mechanisms in brain and peripheral tissues can oscillate independently or be synchronized/disrupted by external stimuli.Dental enamel is a type of mineralized tissue that forms the exterior surface of the tooth crown.Incremental Retzius lines are readily observable microstructures of mature tooth enamel that indicate the regulation of amelogenesis by circadian rhythms.Teeth enamel is formed by enamel-forming cells known as ameloblasts,which are regulated and orchestrated by the circadian clock during amelogenesis.This review will first examine the key roles of the circadian clock in regulating ameloblasts and amelogenesis.Several physiological processes are involved,including gene expression,cell morphology,metabolic changes,matrix deposition,ion transportation,and mineralization.Next,the potential detrimental effects of circadian rhythm disruption on enamel formation are discussed.Circadian rhythm disruption can directly lead to Enamel Hypoplasia,which might also be a potential causative mechanism of amelogenesis imperfecta.Finally,future research trajectory in this field is extrapolated.It is hoped that this review will inspire more intensive research efforts and provide relevant cues in formulating novel therapeutic strategies for preventing tooth enamel developmental abnormalities.

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 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.

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 efficacy of semaglutide in the treatment of type 2 diabetes mellitus(T2DM)com-bined with non-alcoholic fatty liver disease(NAFLD)and its effect on oxidative stress and inflammatory factors.Methods Totally 80 patients with T2DM accompanied by NAFLD admitted to the First Affiliated Hospital of Xinxiang Medical University from July 2021 to December 2022 were selected and randomly assigned to the observation group and the control group,with 40 patients in each group.Patients in the control group were treated with pioglitazone metformin and dapagliflozin,while patients in the observation group were treated with pioglitazone metformin,dapagliflozin,and semaglutide.The levels of glycated hemoglobin(HbA1c),fasting blood glucose(FBG),2-hour postprandial blood glucose(2hPG),body mass,body mass index(BMI),waist circumference,alanine aminotransferase(ALT),aspartate aminotransferase(AST),gamma-glutamyl transferase(GGT),controlled attenuation parameter(CAP),liver stiffness measurement(LSM),malondialdehyde(MDA),glutathione peroxidase(GSH-PX),lipid peroxide(LPO),tumor necrosis factor-α(TNF-α),interleukin-6(IL-6),and interleukin-10(IL-10)before and after the treatment were compared.Results After 24 weeks of treatment,the overall response rate(ORR)in the observation group and control group was 92.5％(37/40)and 72.5％(29/40),respectively;and the ORR in the observation group was significantly higher than that in the control group(x2=5.541,P＜0.05).Before treatment,there was no statistically significant difference in the body mass,BMI,waist circumference,HbA1c,FBG,2hPG,ALT,AST,GGT,CAP,LSM,MDA,GSH-PX,LPO,TNF-α,IL-6,and IL-10 of patients between the 2 groups(P＞0.05);after 24 weeks of treatment,the body mass,BMI,waist circumference,HbA1c,FBG,2hPG,ALT,AST,GGT,CAP,LSM,MDA,LPO,TNF-α,IL-6,and IL-10 were significantly lower than before treatment,while GSH-PX was significantly higher than before treatment(P＜0.05);after 24 weeks of treatment,the body mass,BMI,waist circumference,HbA1c,FBG,2hPG,ALT,AST,GGT,CAP,LSM,MDA,LPO,TNF-α,IL-6,and IL-10 of patients in the observation group were significantly lower than those in the control group,and GSH-PX was significantly higher than that in the control group(P＜0.05).The incidence of adverse reactions in the observation group and the control group during the treatment period was 17.5％(7/40)and 12.5％(5/40),respectively;and the difference in the incidence of adverse reactions between the two groups was not statistically significant(P＞0.05).Conclusion Semaglutide significantly downregulates the levels of FBG,2hPG and HbA1c in patients with T2DM combined with NAFLD and reduces the body mass,waist circumference,liver enzyme level,hepatic fat content,hepatic fibrosis,oxidative stress,and inflammatory indicators.

Objective To explore the therapeutic effects of different doses of radioactive iodine-131 on patients with hyperthyroidism.Methods A total of 574 patients with hyperthyroidism treated in the First Affiliated Hospital of Xinxiang Medical University from April 2020 to April 2023 were sampled for this study and were divided evenly into the observation group and the control group by a random number table,with 287 patients in each group.The control group was treated with high-dose radioactive iodine-131(＞10-15 mCi),while the observation group was provided with low-dose radioactive iodine-131(5-10 mCi).The therapeutic effects were estimated six months after treatment.Data of the two groups of patients before treatment and 3 and 6 months after treatment were compared,including the levels of thyroid hormone(FT4),free triiodothyronine(FT3),and thyroid-stimulating hormone(TSH),which were measured through the fluorescence immunochromatography of serum(obtained by centrifugation of 3 mL fasting venous blood),and the tumor necrosis factor-α(TNF-α),transforming growth factor-β1(TGF-β1),interleukin-6(IL-6),and IL-1,which were measured through the enzyme-linked immunosorbent assay of serum.The salivary gland uptake index and salivary gland secretion index of the patients before treatment and 3 and 6 months after treatment were measured through radionuclide imaging.The incidence of adverse reactions during treatment was documen-ted.The incidence of hypothyroidism in both groups was evaluated 6 months after treatment.Results The total effective rate of the observation group and the control group was 83.27％(234/281)and 92.88％(261/281),respectively,and that of the observation group was significantly higher(x2=12.353,P＜0.05).The FT4,FT3,and TSH levels of the two groups before treatment showed no statistical discrepancy(P＞0.05).According to data collected 3 and 6 months after treatment,FT4 and FT3 levels of both groups significantly decreased,while TSH increased(P＜0.05)compared to corresponding pre-treatment levels;FT4 and FT3 levels of both groups observed 6 months after treatment were significantly lower than those observed 3 months before,in contrast to the growing TSH trend(P＜0.05).At 3 and 6 months after treatment,FT4 and FT3 levels of the observation group were significantly lower than those of the control group,while TSH levels were significantly higher(P＜0.05).The salivary gland uptake index and salivary gland secretion index between the two groups before treatment showed no statistical discrepancy(P＞0.05).At 3 and 6 months after treatment,such indexes of both groups obviously decreased(P＜0.05).However,those observed 6 months after treatment were higher than three months before(P＜0.05).At 3 months after treatment,the salivary gland uptake index and salivary gland secretion index of the observation group were notably higher than the control group(P＜0.05);at 6 months after treatment,no statistical discrepancy was observed between the two groups in terms of the two indexes(P＞0.05).Before treatment,there was no statistical difference in TNF-α,TGF-β1,IL-6,and IL-1 levels between the two groups(P＞0.05).At 3 and 6 months after treatment,the TNF-α,TGF-β1,IL-6,and IL-1 levels of both groups decreased significantly from pre-treatment levels(P＜0.05),and the data observed 6 months after treatment were still lower than those observed 3 months after treatment(P＜0.05).At 3 months after treatment,the TNF-α,TGF-β1,IL-6,and IL-1 levels of the observation group were significantly lower than those of the control group(P＜0.05);at 6 months after treatment,no statistical difference was observed between the two groups(P＞0.05).The incidence of adverse reactions during treatment in the control group and the observation group was 16.38％(47/287)and 8.01％(23/287),respectively,and that of the observation group was significantly lower than the other group(x2=8.457,P＜0.05).At 6 months after treatment,the incidence of hypothyroidism in the control group and the observation group was 12.46％(35/281)and 3.56％(10/281),respectively,and that of the observation group was significantly lower than that in the control group(x2=15.098,P＜0.05).Conclusion Low doses of radioactive iodine-131 work better in the treatment of hyperthyroidism and can effectively alleviate inflammation and salivary gland dysfunction,with less risk of inducing hypothyroidism and adverse reactions.

Objective To develope a clinical decision support system(CDSS)on insulin titration and validate its effectiveness and safety.Methods Eighty patients with type 2 diabetes mellitus treated at the Department of Endocrinology of the First Affiliated Hospital of Xinxiang Medical University from January 2021 to July 2023,who had difficulty in achieving glycemic control on the basis of lifestyle interventions and oral hypoglycemic drug treatments,were selected for the study.The patients were divided into the observation group and the control group using a random number table,with 40 cases in each group.Patients in both groups received oral metformin extended-release tablets,subcutaneous insulin degludec before bedtime,and subcutaneous aspartate insulin injection before three meals for glycemic control.Patients in the observation group were given insulin titration using the CDSS,and patients in the control group were given insulin titration using the conventional method.The retrospective continuous glucose monitoring system was used to monitor time in range(TIR)for glucose,mean amplitude of glycemic excursion(MAGE),mean blood glucose(MBG),standard deviation of blood glucose(SDBG),and the coefficient of variation(CV)of blood glucose.Fasting blood glucose(FBG),2-hour postprandial glucose(2hPG),length of hospitalization,time to achieve standard blood glucose control,and incidence of hypoglycemia of patients were recorded before and after treatment in the two groups.Results There was no significant difference in FBG and 2hPG of patients between the two groups before treat-ment(P＞0.05).The FBG and 2hPG levels of patients in the two groups were significantly lower than those before treatment(P＜0.05).The FBG and 2hPG levels of patients in the observation group were significantly lower than those in the control group after treatment(P＜0.05).TIR of patients in the observation group was significantly higher than that in the control group,while MAGE,MBG,SDBG,and CV were significantly lower than those in the control group after treatment(P＜0.05).The length of hospitalization was 9.0(7.3,10.0)days and 11.0(8.3,12.0)days of patients in the observation group and control group,respectively;and the length of hospitalization of patients in the control group was significantly longer than that in the observation group(Z=-2.408,P＜0.05).The time required to achieve glycemic control was 6.5(5.0,8.8)days and 7.5(6.0,10.0)days of patients in the observation group and control group,respectively;and the time required to achieve glycemic control of patients in the control group was significantly longer than that in the observation group(Z=-2.019,P＜0.05).The incidence of hypoglycemia of patients in the observation group and control group was 20.0％(8/40),12.5％(5/40),respectively;there was no significant difference in the incidence of hypoglycemia between the observation group and the control group(x2=0.827,P＞0.05).Conclusion Compared with the conventional titration of insulin,the application of CDSS can provide decision support during the implementation of a basal-meal insulin regimen,which can lead to more effective glycemic control,improved glucose TIR,reduced glycemic fluctuations,shorter time required for patients to achieve glycemic control,and shorter hospital stays without increasing the risk of hypoglycemia.

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.