Oxidative stress due to aberrant metabolism is considered as a crucial contributor to diabetes and its complications. Hyperglycemia and hyperlipemia boost excessive reactive oxygen species generation by elevated mitochondrial respiration, increased nicotinamide adenine dinucleotide phosphate oxidase activity, and enhanced pro-oxidative processes, including protein kinase C pathways, hexosamine, polyol, and advanced glycation endproducts, which exacerbate oxidative stress. Oxidative stress plays a significant role in the onset of diabetes and its associated complications by impairing insulin production, increasing insulin resistance, maintaining hyperglycemic memory, and inducing systemic inflammation. A more profound comprehension of the molecular processes that link oxidative stress to diabetes is crucial to new preventive and therapeutic strategies. Therefore, this review discusses the mechanisms underlying how oxidative stress contributes to diabetes mellitus and its complications. We also summarize the current approaches for prevention and treatment by targeting the oxidative stress pathways in diabetes.
Oxidative Stress/physiology* ; Humans ; Diabetes Mellitus/physiopathology* ; Diabetes Complications/metabolism* ; Reactive Oxygen Species/metabolism* ; Glycation End Products, Advanced/metabolism* ; Animals

Objective To investigate the effects of Caenorhabditis elegans(C.elegans)endogenous U6 promoters on dpy-10 gene editing efficiency.Methods We screened endogenous U6 small nuclear RNA(snRNA)genes of C.elegans from the WormBase database and constructed 14 editing plasmids targeting dpy-10 by replacing the U6r07e5.16 promoter in the pSX524 plasmid(Peft-3::cas9::tbb-2 terminator::U6 r07e5.16::dpy-10 sgRNA)through molecular cloning.Gene editing was performed in wild-type C.elegans using a standardized microinjection protocol.Gene editing efficiency and the high-efficiency gene editing index were quantified based on the screening of dpy-10 mutant phenotypes in the F1 progeny.Results A total of 15 U6 snRNA genes(r07e5.16,f35c11.9,t20d3.13,k09b11.15,k09b11.16,w05b2.8,c28a5.7,f54c8.9,k09b11.11,k09b11.12,k09b11.14,t20d3.12,f54c8.8,f54c8.10,and k09b11.13)were identified from the WormBase database.Based on the editing efficiency and high-efficiency gene editing index,the activity of these promoters was evaluated,and 4 U6 promoters(w05b2.8,c28a5.7,f54c8.9,and k09b11.11)were found to have significantly enhanced gene editing success rates,outperforming other promoters,including U6r07e5.16 and U6k09b11.12,which are commonly used in the C.elegans research community.Notably,the gRNAF+E scaffold did not show superior editing efficiency over the gRNA scaffold when paired with the optimal U6w05b2.8 promoter.Conclusion In this study,U6 promoters that significantly improve gene editing efficiency in C.elegans are identified and the critical role of promoter optimization in CRISPR-Cas9 systems is highlighted.These findings provide a valuable foundation for improving genome editing strategies and offer new ideas for optimizing the CRISPR technology applied in nematode research.

Objective To optimize the real-time quantitative polymerase chain reaction(RT-qPCR)data analysis process through mathematical principles by replacing the biased 2-??CT method with a more rigorous 2-CT method,thereby improving the accuracy of gene expression quantification analysis.Methods Essentially,the CT value serves as the exponent in a base-2 exponential equation within the logic of comparative CT method.In the traditional 2-??CT method,the arithmetic means of raw CT and ΔCT values are directly calculated and the exponential nature of CT data is overlooked,which may introduce systematic bias to the calculation results.We propose a new method,entitled the 2-CT method,in which all calculations are based on the transformation of CT values into 2-CT.This includes computing the relative initial expression levels of target and reference genes within each sample,the relative abundance of the target gene,and its fold change across groups.Statistical comparisons are then performed based on fold change values.By strictly adhering to the exponential nature of of CT values,the biases introduced by arithmetic averaging at the CT or ΔCT level are avoided.We applied this method to multiple RT-qPCR datasets to evaluate the differences between the traditional 2-??CT and the proposed 2-CT methods in gene expression quantification,as well as the effect of the differences.Results In the original dataset from LIVAK and SCHMITTGEN,the two methods produced similar results.However,in the cadmium exposure experiment,findings from the 2-??CT method indicated that 8-hour cadmium exposure caused an increase of irg-6 gene expression in Caenorhabditis elegans from 1.314-fold to 7.125-fold(P=0.000 2).In contrast,findings from the 2-CT method showed a fold change from 1.0 to 4.124(P=0.001 5),a 70%difference between the two methods.Conclusion The2-CT method provides a mathematically more rigorous approach that more accurately reflects gene expression changes,particularly in experiments with high CT variability.It offers a more reliable computational paradigm for quantitative gene expression analysis.

Objectives:To examine the clinicopathological characteristics and the influencing factors of the residual tumor of patients with Breast Image Report and Data System (BI-RADS) grade 3 lesions diagnosed with malignancy after minimally invasive excision.Methods:In this retrospective case-control study, clinicopathological data of 69 cases, which had been evaluated as BI-RADS 3 lesions by ultrasound (4 151 cases) diagnosed with breast cancer by minimally invasive excision pathology, were analyzed between May 2012 and June 2016 at the Department of Breast Surgery of the Second Hospital of Shandong University and Linyi People′s Hospital. All patients were female, aged (43.4±8.2) years (range: 22 to 70 years). Based on residual tumor after minimally invasive excision, patients were classified into two subgroups: tumor residual group ( n=39) and non-tumor residual group ( n=30). The clinicopathological features between the two groups were compared. The differences in clinicopathological characteristics were compared in different groups using the χ 2 test and the t test. Potential variables identified in the univariate analysis and other relevant variables will be analyzed multivarially using Logistic regression models. The Kaplan-Meier method was applied for survival analysis and survival curves. Results:The breast cancer detection rate of ultrasound BI-RADS 3 lesions was 1.66% (69/4 151), and their maximum diameter of the masses was (1.27±0.45) cm (range: 0.5 to 2.3 cm). Among them, the maximum diameter were ≤1 cm in 28 cases and >1 cm in 41 cases. Histopathological results showed carcinoma in situ in 24 cases and invasive carcinoma in 41 cases, positive expression of the estrogen receptor in 47 cases, positive expression of the progesterone receptor in 43 cases, Ki-67 proliferation index elevated in 26 cases. Axillary metastasis positive rate was 10.1% (7/69). Residual tumor after minimally invasive surgery was found in 39 cases (56.5%). Univariate analysis showed that the tumour residual group showed a significantly increased rate of positive expression of the estrogen receptor (91.9%(34/37) vs. 61.9%(13/21), χ2=7.838, P=0.012). In multivariate analysis, the only variable found to significantly affect the residual tumor was the positive expression of the estrogen receptor ( OR=16.852, 95% CI: 1.819 to 156.130, P=0.013). The 5-year disease-free survival rate of breast cancer patients with breast ultrasound BI-RADS 3 lesions was 97.1% and the overall survival rate was 98.6%. Conclusions:BI-RADS 3 lesions diagnosed by ultrasound undergoing ultrasound-guided minimally invasive excision have a certain risk of detected malignancy, approximately 1.66%. Patients with positive expression of the estrogen receptor are more likely to develop residual tumor. A secondary operation should be considered to ensure that no tumor residues remain in the cavity.

Objectives:To examine the clinicopathological characteristics and the influencing factors of the residual tumor of patients with Breast Image Report and Data System (BI-RADS) grade 3 lesions diagnosed with malignancy after minimally invasive excision.Methods:In this retrospective case-control study, clinicopathological data of 69 cases, which had been evaluated as BI-RADS 3 lesions by ultrasound (4 151 cases) diagnosed with breast cancer by minimally invasive excision pathology, were analyzed between May 2012 and June 2016 at the Department of Breast Surgery of the Second Hospital of Shandong University and Linyi People′s Hospital. All patients were female, aged (43.4±8.2) years (range: 22 to 70 years). Based on residual tumor after minimally invasive excision, patients were classified into two subgroups: tumor residual group ( n=39) and non-tumor residual group ( n=30). The clinicopathological features between the two groups were compared. The differences in clinicopathological characteristics were compared in different groups using the χ 2 test and the t test. Potential variables identified in the univariate analysis and other relevant variables will be analyzed multivarially using Logistic regression models. The Kaplan-Meier method was applied for survival analysis and survival curves. Results:The breast cancer detection rate of ultrasound BI-RADS 3 lesions was 1.66% (69/4 151), and their maximum diameter of the masses was (1.27±0.45) cm (range: 0.5 to 2.3 cm). Among them, the maximum diameter were ≤1 cm in 28 cases and >1 cm in 41 cases. Histopathological results showed carcinoma in situ in 24 cases and invasive carcinoma in 41 cases, positive expression of the estrogen receptor in 47 cases, positive expression of the progesterone receptor in 43 cases, Ki-67 proliferation index elevated in 26 cases. Axillary metastasis positive rate was 10.1% (7/69). Residual tumor after minimally invasive surgery was found in 39 cases (56.5%). Univariate analysis showed that the tumour residual group showed a significantly increased rate of positive expression of the estrogen receptor (91.9%(34/37) vs. 61.9%(13/21), χ2=7.838, P=0.012). In multivariate analysis, the only variable found to significantly affect the residual tumor was the positive expression of the estrogen receptor ( OR=16.852, 95% CI: 1.819 to 156.130, P=0.013). The 5-year disease-free survival rate of breast cancer patients with breast ultrasound BI-RADS 3 lesions was 97.1% and the overall survival rate was 98.6%. Conclusions:BI-RADS 3 lesions diagnosed by ultrasound undergoing ultrasound-guided minimally invasive excision have a certain risk of detected malignancy, approximately 1.66%. Patients with positive expression of the estrogen receptor are more likely to develop residual tumor. A secondary operation should be considered to ensure that no tumor residues remain in the cavity.

Objective To study the effectiveness of pro-abdominal exercise in improving the quality of gastroscopy,and provide patients with a better preoperative preparation for gastroscopy.Methods 307 patients who underwent painless gastroscopy from March to July 2023 were selected and divided into three groups according to the random number table method.There were 106 cases in the abdominal massage group,103 cases in the bed turning group and 98 cases in the control group.On the basis of routine medication,different preoperative activity guidance was used to compare and analyze the preoperative preparation time,examination time and gastric mucosal visual field clarity score in each group.Results The gastroscopy time in the abdominal massage group and the bed-turning group was significantly shorter than that in the control group,and the clarity score of the gastric mucosal visual field was significantly lower than that of the control group,with statistically significant differences(P<0.05).However,there were no statistically significant differences in the gastroscopy time or visual field clarity score for gastric body,gastric fundus,and gastric antrum between the abdominal massage group and the bed-turning group(P>0.05).The satisfaction rate of endoscopists in the abdominal massage group and the bed turning group was higher than that in the control group,and the differences were statistically significant.Conclusion Abdominal massage and turning over in bed as preoperative preparation methods for gastroscopy can improve the quality of gastroscopy,while abdominal massage can shorten the preparation time before gastroscopy,which is helpful for the efficient operation of digestive endoscopy center and is worthy of clinical application.

Objective To evaluate the impact of the WeChat platform health management model combined with low-dose atorvastatin on lipid and glucose profiles,quality of life,and negative emotions in patients with metabolic syndrome and obesity.Methods The data of obese patients with metabolic syndrome who were treated at Shangyu People's Hospital of Shaoxing from June 2022 to June 2023 were retrospectively analyzed.The patients were divided into a control group and an experimental group according to their out-of-hospital health management methods.The control group received atorvastatin combined with conventional health management treatment,and the experimental group received atorvastatin combined with a health management model based on the WeChat platform.The blood glucose and lipid-related indicators were compared between the two groups before and 3 months and 6 months after intervention.Negative emotions and quality of life were compared before and 6 months after intervention,and self-management ability was compared 6 months after intervention.Results A total of 160 patients were included in the study,with 85 patients in the control group and 75 patients in the experimental group.After the intervention,the fasting blood glucose(FBG),2-hour postprandial blood glucose(2hPBG),glycated hemoglobin(HbA1c),low-density lipoprotein(LDL-C),triglyceride(TG)and total cholesterol(TC)of the two groups of patients at 3 months and 6 months)were significantly lower than before intervention,and the above indicators of the experimental group were lower than those of the control group(P＜0.05);while high-density lipoprotein(HDL-C)was significantly higher than that before intervention,and HDL-C in the observation group was higher than that of the control group(P＜0.05).Compared with pre-treatment,the anxiety self-rating scale(SAS)and depression self-rating scale(SDS)scores were siginficantly lower,and various quality of life scores for both groups significantly higher 6 months after intervention(P＜0.05),and the self-management ability of the experimental group was significantly higher than that of the control group(P＜0.05).Conclusion Low-dose atorvastatin combined with the WeChat platform health management model effectively improves lipid profiles,blood glucose,negative emotions,self-management behavior,and quality of life in patients with metabolic syndrome and obesity,which is worthy of clinical promotion.

ObjectiveTo investigate the effect of 1 Hz repetitive transcranial magnetic stimulation (rTMS) combined with mirror therapy on upper limb motor function and cortical neurophysiological indicators in stroke patients with hemiplegia. MethodsSixty stroke patients who were admitted to Jinshan Hospital of Fudan University, from October, 2022 to March, 2023 were randomly assigned to control group (n = 15), rTMS group (n = 15), mirror therapy group (n = 15) and combined group (n = 15). All groups received routine medicine and rehabilitation. In addition, the control group received sham rTMS and sham mirror therapy, rTMS group received 1 Hz rTMS and sham mirror therapy, the mirror therapy group received sham rTMS and mirror therapy, and the combined group received 1Hz rTMS combined with mirror therapy, for four weeks. Fugl-Meyer Assessment-Upper Extremities (FMA-UE) and Action Research Arm Test (ARAT) were used to evaluate the motor function of the affected upper limb. The motor-evoked potential (MEP) amplitude and central motor conduction time (CMCT) of the affected cortex were measured using a transcranial magnetic stimulation device. ResultsAfter treatment, the scores of FMA-UE and ARAT, and the amplitude of MEP significantly improved in all groups (|t| > 3.854, P < 0.001), while the CMCT significantly shortened (t > 5.967, P < 0.001). Compared to the control group, rTMS group, the mirror therapy group and the combined group showed more significant improvement in the scores of FMA-UE and ARAT, and the amplitude of MEP, and shorter CMCT (P < 0.05). When compared to rTMS group and the mirror therapy group, the combined group showed more significant improvement the scores of FMA-UE and ARAT, and the amplitude of MEP, and shorter CMCT (P < 0.05). There was significant positive correlation of the scores of FMA-UE and ARAT with the amplitude of MEP, and negative correlation with the CMCT in all groups (R² > 0.804, P < 0.001). ConclusionThe combination of 1 Hz rTMS and mirror therapy contributes to the post-stroke brain functional remodeling and facilitates upper limb motor recovery in stroke patients with hemiplegia.

Objective To study the validity period of sterilized medical supplies packed by non-woven fabric or disposable paper-plastic packages and placed in different battle positions and storage conditions during long-distance navigation.Methods After autoclaving,the non-woven fabrics and paper-plastic packages stored in different battle positions on ships with different batches were tested for sterility,the validity period of the two packaging methods was determined,and the data were analysed.Results On the 150th day after sterilization,bacteria began to grow on the medical supplies packed by both packages in the machine room and engine room.On the 165th day after sterilization,bacteria began to grow on the non-woven packaging items in the dental room.On the 180th day after sterilization,bacteria began to grow on the paper plastic packaging items in the clinic(reception room).On the 180th day after sterilization,the medical supplies packed by both packages in the operation room had no bacteria growth.There was no significant difference in the validity period of sterilized medical supplies between disposable paper-plastic and non-woven packages in the same battle position(P>0.05).There was no significant difference in the validity period of sterilized medical supplies between medical clinic,dental room,and operation room(P>0.05),but there were significant differences between machine room,engine room,and operation room(P<0.05).Conclusion The term of validity of medical supplies packaged with disposable paper-plastic and non-woven fabric packages sterilized by autoclaving is both within 135 days,and there is no significant difference in the validity period date between the two packaging methods.

Objective:To observe the ratio of helper T cells 17 (Th17)/regulatory T cells (Treg) in peripheral blood of patients with Hashimoto's thyroiditis (HT) and the expression changes of related cytokines in serum, and to explore their role in the occurrence and development of HT.Methods:Using the case-control study method, 35 HT patients examined in the General Hospital of Heilongjiang Beidahuang Group from February to November 2019 were selected as HT group, and 39 healthy people in the same period were selected as control group. Early morning fasting venous blood samples of the two groups were collected to test the levels of thyroid stimulating hormone (TSH), free thyroxine (FT 4), thyroid peroxidase antibody (TPOAb) and thyroglobulin antibody (TgAb). The expressions of serum interleukin (IL)-6, IL-17 and transforming growth factor β (TGF-β) were tested by enzyme-linked immunosorbent assay (ELISA); the number of Th17, Treg in peripheral blood were determined by flow cytometry. Results:The levels of TPOAb, TgAb and TSH in HT group [130.60 (43.37, 714.40), 368.10 (136.90, 1 103.00) U/ml, 9.05 (6.62, 15.23) μU/ml] were significantly higher than those in control group [2.66 (1.52, 4.69), 12.63 (11.43, 14.60) U/ml, 1.87 (1.36, 2.23) μU/ml, U = 6.87, 6.62, 4.85, P < 0.001], and the FT 4 level [0.76 (0.63, 1.04) ng/dl] was lower than that in control group [1.14 (1.02, 1.26) ng/dl, U = 7.39, P < 0.001]. The expressions of IL-6, IL-17 and TGF-β in HT group were higher than those in control group ( t = 2.41, 9.04, 2.44, P < 0.05). The number of Th17 and the ratio of Th17/Treg in HT group were higher than those in control group ( t = 4.20, 3.50, P < 0.05), and the number of Treg was lower than that in control group ( t = 4.45, P = 0.001). Conclusion:In HT patients, Th17 are increased, Treg decreased, Th17/Treg ratio increased, and the expressions of IL-6, IL-17 and TGF-β are increased.