Objective:To investigate the relationship between glycated hemoglobin (HbA1c) level and the occurrence of diabetes complications in patients with type 2 diabetes mellitus in 11 provinces in China.Methods:A total of 4 832 patients with type 2 diabetes mellitus from 60 surveillance sites in 11 provinces where national surveillance for chronic diseases and risk factors was conducted in 2010 were selected as the study participants, and a follow-up survey was conducted in 3 516 persons from 2016 to 2017, finally 3 427 patients were included in the analysis after excluding those data exception and incomplete data. Cox proportional risk regression model was used to evalaute the association between HbA1c level and the risk for diabetes complications (macroangiopathy, microangiopathy and diabetic foot), and subgroup analyses were conducted according to the baseline characteristics of the study participants, such as age, gender and smoking status.Results:A total of 3 427 study participants were included in final analysis of the follow up for an average of 6.2 years, in whom 395 suffered from macroangiopathy, 226 suffered from microangiopathy, and 57 suffered from diabetic foot later during the follow-up period. After adjusting for relevant confounders, using the HbA1c <7.0% as a reference, there was no increased risk for macrovascular lesions in the those with HbA1c levels of 7.0%-, 7.5%-, 8.0%-8.4%, and the risk for macrovascular lesions increased by 38% in those with HbA1c ≥8.5% ( HR=1.38,95% CI:1.06-1.80); the risk for microangiopathies increased by 131% ( HR=2.31,95% CI:1.46-3.65), 206%( HR=3.06,95% CI:1.91-4.90) and 208% ( HR=3.08,95% CI:2.20-4.30) in those with HbA1c levels of 7.5%-, 8.0%-, ≥8.5%, respectively; and the risk for diabetic foot increased by 253% ( HR=3.53, 95% CI: 1.89-6.59) in those with HbA1c level ≥8.5%. Subgroup analyses revealed an effect modifying effect of different diabetes diagnosis situations (previously diagnosed and newly diagnosed) on HbA1c level and the risk for microangiopathy. Conclusions:HbA1c level ≥7.5% would increase the risk for microangiopathy in patients with type 2 diabetes mellitus, the higher the level, the higher the risk, and HbA1c level ≥8.5% would increase the risk for macrovascular lesions and diabetic foot. It is necessary to strengthen the health education in diabetic patients to improve their awareness of blood glucose management and the importance of HbA1c level control to effectively reduce or delay the diabetes complications.

AIM:This study aims to investigate whether triiodothyronine(T3)can enhance skin wound heal-ing by activating the the cyclic guanosine monophosphate-adenosine monophosphate synthase(cGAS)-stimulator of inter-feron genes(STING)signaling pathway to modulate the inflammatory phase.METHODS:Mice were randomly assigned to five groups:normal,control,T3,RU.521+T3,and RU.521(a cGAS inhibitor).With the exception of the normal group,a full-thickness skin defect model was established in the other groups.Wound healing was observed daily.Mice were euthanized on post-injury days 1,2,4,7,and 10,with five mice per group.Pathological changes and collagen fiber formation were assessed using hematoxylin-eosin(HE)and Masson staining,respectively.Immunohistochemical staining was performed to evaluate the expression of cGAS,STING,mouse EGF-like module-containing mucin-like hormone recep-tor-like 1(EMR1 or F4/80),C-X-C motif chemokine ligand 8(CXCL-8),and CXCL-10.Western blotting was conducted to measure protein levels of cGAS,STING,C-C motif chemokine ligand-2(CCL-2),and nuclear factor-κB(NF-κB).En-zyme linked immunosorbent assay(ELISA)was utilized to quantify the levels of interferon-β(IFN-β),interleukin-6(IL-6),and tumor necrosis factor α(TNF-α).RESULTS:From days 1 to 4 post-injury,the wound healing rate and collagen fiber formation in the T3 group were significantly greater than those in the control,RU.521+T3,and RU.521 groups(P＜0.05).Additionally,the T3 group displayed more favorable pathological changes compared to the other groups.No ex-pression of cGAS and STING was observed in the normal group,while low levels were found in the RU.521+T3 and RU.521 groups.The T3 and control groups exhibited higher expression levels,with the T3 group showing significantly ele-vated expression on days 1 to 4 post-injury(P＜0.05)but lower expression on day 7 compared to the control group(P＜0.05).The expression of the macrophage marker F4/80 was higher in the T3 group compared to the control,RU.521+T3,and RU.521 groups on days 1 to 7 post-injury(P＜0.05).Furthermore,chemokines CXCL-8,CXCL-10,and CCL-2 showed increased levels in the T3 group on days 1 to 2 or 1 to 4 post-injury(P＜0.05)but were lower at other time points(P＜0.05)compared with the control,RU.521+T3,and RU.521 groups.Additionally,the levels of pro-inflammatory fac-tors IFN-β,IL-6,TNF-α,and NF-κB in the T3 group were significantly higher on day 1 post-injury(P＜0.05),while lev-els on days 2 to 7 were lower compared to the control,RU.521+T3,and RU.521 groups(P＜0.05).CONCLUSION:T3 accelerates the healing of impaired skin wounds,potentially through the enhanced activation of the cGAS-STING signal-ing pathway.This process increases the expression of chemokines and pro-inflammatory factors and promotes macrophage recruitment during the early post-injury phase,ultimately regulating the inflammatory response.

Objective:To investigate the relationship between glycated hemoglobin (HbA1c) level and the occurrence of diabetes complications in patients with type 2 diabetes mellitus in 11 provinces in China.Methods:A total of 4 832 patients with type 2 diabetes mellitus from 60 surveillance sites in 11 provinces where national surveillance for chronic diseases and risk factors was conducted in 2010 were selected as the study participants, and a follow-up survey was conducted in 3 516 persons from 2016 to 2017, finally 3 427 patients were included in the analysis after excluding those data exception and incomplete data. Cox proportional risk regression model was used to evalaute the association between HbA1c level and the risk for diabetes complications (macroangiopathy, microangiopathy and diabetic foot), and subgroup analyses were conducted according to the baseline characteristics of the study participants, such as age, gender and smoking status.Results:A total of 3 427 study participants were included in final analysis of the follow up for an average of 6.2 years, in whom 395 suffered from macroangiopathy, 226 suffered from microangiopathy, and 57 suffered from diabetic foot later during the follow-up period. After adjusting for relevant confounders, using the HbA1c <7.0% as a reference, there was no increased risk for macrovascular lesions in the those with HbA1c levels of 7.0%-, 7.5%-, 8.0%-8.4%, and the risk for macrovascular lesions increased by 38% in those with HbA1c ≥8.5% ( HR=1.38,95% CI:1.06-1.80); the risk for microangiopathies increased by 131% ( HR=2.31,95% CI:1.46-3.65), 206%( HR=3.06,95% CI:1.91-4.90) and 208% ( HR=3.08,95% CI:2.20-4.30) in those with HbA1c levels of 7.5%-, 8.0%-, ≥8.5%, respectively; and the risk for diabetic foot increased by 253% ( HR=3.53, 95% CI: 1.89-6.59) in those with HbA1c level ≥8.5%. Subgroup analyses revealed an effect modifying effect of different diabetes diagnosis situations (previously diagnosed and newly diagnosed) on HbA1c level and the risk for microangiopathy. Conclusions:HbA1c level ≥7.5% would increase the risk for microangiopathy in patients with type 2 diabetes mellitus, the higher the level, the higher the risk, and HbA1c level ≥8.5% would increase the risk for macrovascular lesions and diabetic foot. It is necessary to strengthen the health education in diabetic patients to improve their awareness of blood glucose management and the importance of HbA1c level control to effectively reduce or delay the diabetes complications.

AIM:This study aims to investigate whether triiodothyronine(T3)can enhance skin wound heal-ing by activating the the cyclic guanosine monophosphate-adenosine monophosphate synthase(cGAS)-stimulator of inter-feron genes(STING)signaling pathway to modulate the inflammatory phase.METHODS:Mice were randomly assigned to five groups:normal,control,T3,RU.521+T3,and RU.521(a cGAS inhibitor).With the exception of the normal group,a full-thickness skin defect model was established in the other groups.Wound healing was observed daily.Mice were euthanized on post-injury days 1,2,4,7,and 10,with five mice per group.Pathological changes and collagen fiber formation were assessed using hematoxylin-eosin(HE)and Masson staining,respectively.Immunohistochemical staining was performed to evaluate the expression of cGAS,STING,mouse EGF-like module-containing mucin-like hormone recep-tor-like 1(EMR1 or F4/80),C-X-C motif chemokine ligand 8(CXCL-8),and CXCL-10.Western blotting was conducted to measure protein levels of cGAS,STING,C-C motif chemokine ligand-2(CCL-2),and nuclear factor-κB(NF-κB).En-zyme linked immunosorbent assay(ELISA)was utilized to quantify the levels of interferon-β(IFN-β),interleukin-6(IL-6),and tumor necrosis factor α(TNF-α).RESULTS:From days 1 to 4 post-injury,the wound healing rate and collagen fiber formation in the T3 group were significantly greater than those in the control,RU.521+T3,and RU.521 groups(P＜0.05).Additionally,the T3 group displayed more favorable pathological changes compared to the other groups.No ex-pression of cGAS and STING was observed in the normal group,while low levels were found in the RU.521+T3 and RU.521 groups.The T3 and control groups exhibited higher expression levels,with the T3 group showing significantly ele-vated expression on days 1 to 4 post-injury(P＜0.05)but lower expression on day 7 compared to the control group(P＜0.05).The expression of the macrophage marker F4/80 was higher in the T3 group compared to the control,RU.521+T3,and RU.521 groups on days 1 to 7 post-injury(P＜0.05).Furthermore,chemokines CXCL-8,CXCL-10,and CCL-2 showed increased levels in the T3 group on days 1 to 2 or 1 to 4 post-injury(P＜0.05)but were lower at other time points(P＜0.05)compared with the control,RU.521+T3,and RU.521 groups.Additionally,the levels of pro-inflammatory fac-tors IFN-β,IL-6,TNF-α,and NF-κB in the T3 group were significantly higher on day 1 post-injury(P＜0.05),while lev-els on days 2 to 7 were lower compared to the control,RU.521+T3,and RU.521 groups(P＜0.05).CONCLUSION:T3 accelerates the healing of impaired skin wounds,potentially through the enhanced activation of the cGAS-STING signal-ing pathway.This process increases the expression of chemokines and pro-inflammatory factors and promotes macrophage recruitment during the early post-injury phase,ultimately regulating the inflammatory response.

Objective:In chronic hepatitis B (CHB) patients with previous 96-week treatment with tenofovir amibufenamide (TMF) or tenofovir disoproxil fumarate (TDF), we investigated the efficacy of sequential TMF treatment from 96 to 144 weeks.Methods:Enrolled subjects who were previously assigned (2:1) to receive either 25 mg TMF or 300 mg TDF with matching placebo for 96 weeks received extended or switched TMF treatment for 48 weeks. Efficacy was evaluated based on virological, serological, biological parameters, and fibrosis staging. Statistical analysis was performed using the McNemar test, t-test, or Log-Rank test according to the data. Results:593 subjects from the initial TMF group and 287 subjects from the TDF group were included at week 144, with the proportions of HBV DNA<20 IU/ml at week 144 being 86.2% and 83.3%, respectively, and 78.1% and 73.8% in patients with baseline HBV DNA levels ≥8 log10 IU/ml. Resistance to tenofovir was not detected in both groups. For HBeAg loss and seroconversion rates, both groups showed a further increase from week 96 to 144 and the 3-year cumulative rates of HBeAg loss were about 35% in each group. However, HBsAg levels were less affected during 96 to 144 weeks. For patients switched from TDF to TMF, a substantial further increase in the alanine aminotransferase (ALT) normalization rate was observed (11.4%), along with improved FIB-4 scores.Conclusion:After 144 weeks of TMF treatment, CHB patients achieved high rates of virological, serological, and biochemical responses, as well as improved liver fibrosis outcomes. Also, switching to TMF resulted in significant benefits in ALT normalization rates (NCT03903796).

Objective:In chronic hepatitis B (CHB) patients with previous 96-week treatment with tenofovir amibufenamide (TMF) or tenofovir disoproxil fumarate (TDF), we investigated the safety profile of sequential TMF treatment from 96 to 144 weeks.Methods:Enrolled subjects that previously assigned (2:1) to receive either 25 mg TMF or 300 mg TDF with matching placebo for 96 weeks received extending or switching TMF treatment for 48 weeks. Safety profiles of kidney, bone, metabolism, body weight, and others were evaluated.Results:666 subjects from the initial TMF group and 336 subjects from TDF group with at least one dose of assigned treatment were included at week 144. The overall safety profile was favorable in each group and generally similar between extended or switched TMF treatments from week 96 to 144. In subjects switching from TDF to TMF, the non-indexed estimated glomerular filtration rate (by non-indexed CKD-EPI formula) and creatinine clearance (by Cockcroft-Gault formula) were both increased, which were (2.31±8.33) ml/min and (4.24±13.94) ml/min, respectively. These changes were also higher than those in subjects with extending TMF treatment [(0.91±8.06) ml/min and (1.30±13.94) ml/min]. Meanwhile, switching to TMF also led to an increase of the bone mineral density (BMD) by 0.75% in hip and 1.41% in spine. On the other side, a slight change in TC/HDL ratio by 0.16 (IQR: 0.00, 0.43) and an increase in body mass index (BMI) by (0.54±0.98) kg/m 2 were oberved with patients switched to TMF, which were significantly higher than that in TMF group. Conclusion:CHB patients receiving 144 weeks of TMF treatment showed favorable safety profile. After switching to TMF, the bone and renal safety was significantly improved in TDF group, though experienceing change in metabolic parameters and weight gain (NCT03903796).

Objective:To investigate the application of patient-based real-time quality control (PBRTQC) using exponentially weighted moving average (EWMA) method in internal quality control (IQC) procedures of thyroid function tests.Methods:The serum thyroid function test results of outpatients and inpatients in the Second Hospital of Shandong University from December 1, 2022 to April 30, 2023 were collected. Based on the PBRTQC professional intelligent software system, normality correction, parameter setting, program preparation and real-time operation of test data were carried out. The results of all patients who underwent thyroid function testing between May 1, 2023 and August 31, 2023 were used as the validation dataset. The estimated EWMA value of thyroid function test results and the cumulative coefficient of variation ( CV) over 4 months were calculated. The cumulative CV was compared with the criteria of precision quality standard (1/3TEa) and the CV of IQC. Westgard 2-2s and 1-3s rules were used for alarm setting. The early warning information of the EWMA quality control program were recorded and the potential causes of performance changes were analyzed. DxLab Mind software was used to conduct normal distribution statistics for all data, and the Kolmogorov-Smirnov test was performed on the test results. Results:The items related to serum thyroid function of the patients were all positively skewed. After data correction by Box-Cox method, the PBRTQC data of free triiodothyronine (FT3) and free thyroxine (FT4) were normally distributed, and their cumulative precisions ( CV) of EWMA within 4 months were 6.26% and 2.86%, respectively, both of which were lower than the precision quality target of 8.33%. However, the data of thyroid-stimulating hormone (TSH), thyroid peroxidase antibodies (TPOAb) and thyroglobulin antibody (TgAb) were still positive skewed after modification. The EWMA cumulative CV of TSH, TPOAb and TgAb were 13.16%, 15.31% and 16.77%, which were higher than the precision quality targets of 8.33%, 10% and 10%, respectively. The EWMA QC program can detect different out-of-control alarms, including FT4 false alarms due to sample source concentration and TSH result bias caused by changes in reagent performance. In addition, the EWMA QC program can also detect differences in FT3 results between different DXI800 fully automated chemiluminescence instrument instruments. Conclusions:The EWMA program based on PBRTQC professional intelligent software tools can monitor the patient data of the detection system in real time and continuously, dynamically identify and monitor the errors generated during the analysis process and give early warning. It can be used as a useful supplement for the daily IQC of thyroid function items, especially FT3 and FT4, and has good clinical application value.

Bariatric surgery is the most effective treatment for patients with severe obesity, which can significantly improve the metabolic disorders, especially type 2 diabetes mellitus. Bariatric and metabolic surgery is the latest and fastest-growing branch of surgery, with the types of procedure and other novel treatment modalities are still evolving and in progress. The authors summarize the recent advancement related to novel bariatric and metabolic surgery in the treat-ment of morbid obesity and type 2 diabetes mellitus in recent years through literature search, which can be divided into the following three parts: (1) novel surgical procedures and new guideline of indication. Sleeve gastrectomy and Roux-en-Y gastric bypass are the most performed bariatric surgery. Duodenal switch or the variant of one anastomosis duodenal ileostomy are also accredited procedures but been less performed. One anastomosis gastric bypass is the most recently accredited bariatric surgical procedures with better safety profile and weight loss efficacy than most of the procedures. For other novel procedures, bipartition procedure may be the next accredited proce-dure. A new worldwide guideline is recently launched and the indication for bariatric surgery is lowered BMI 27.5 kg/m 2 for Asian. (2) The effect and mechanism of bariatric surgery. Bariatric surgery can significantly reduce the incidence of cardiovascular disease and mortality in obese patients. The main beneficiary group is patients with diabetes mellitus. Along with the recent basic research and the success of new gut hormone related drugs, the mechanism of bariatric surgery can be mostly attributed to gut hormonal effect, however, gastric volume still play an important role. (3) Novel obesity treatment modalities. Endoscopic obesity treatment has a major progress in the success of endoscopic gastroplasty by endoscopic suturing designs. More noteworthy is the development of new intestinal hormone drug therapy, which can achieve a weight loss of 14% in one year by injec-ting once a week glucagon-like peptide-1 preparation, and then combining two or three intestinal hormone drugs can achieve a weight loss of 24% in one year, which is close to the effectiveness of bariatric surgery. Pharmacologic treatment of obesity is very promising and expected. With the increasing severity of obesity and diabetes mellitus in the world, in addition to the explosive develo-pment of bariatric and metabolic surgery in recent years, many new surgical methods and new treatments, especially new and effective intestinal hormone related therapeutic drugs, have been developed. The success of bariatric and metabolic surgery depends on a multidisciplinary team with rich clinical experience: precise preoperative planning and comprehensive postoperative manage-ment, as well as patient understanding and cooperation, in order to achieve the best results.

Objective:To compare the consistency of preoperative frailty assessment in elderly colorectal cancer patients using Frailty Phenotype (FP), FRAIL Scale (FS), Clinical Frailty Scale (CFS), and Edmonton Frailty Scale (EFS), and their predictive performance in predicting the postoperative complication, so as to provide reference for nurses to choose appropriate frailty assessment tools.Methods:From December 2020 to October 2021, 207 elderly patients who underwent radical surgery for colorectal cancer at the General Surgery of the First Affiliated Hospital of Soochow University were selected as the study subject by convenience sampling. FP, FS, CFS, and EFS were used to assess patients' frailty. Taking postoperative complications as the outcome indicator, the predictive performance of four frailty assessment tools was compared using the receiver operating characteristic (ROC) curve and Bayes discriminant analysis.Results:The frailty detection rates of FP, FS, CFS, and EFS in 207 elderly colorectal cancer patients were 19.8% (41/207), 11.6% (24/207), 22.2% (46/207), and 10.1% (21/207), respectively. The areas under the ROC curves of FP, FS, CFS, and EFS were 0.714, 0.643, 0.737, and 0.665, respectively, with statistically significant differences (all P<0.01). Pairwise comparison found that there were statistically significant differences in the area under the ROC curve between FP and FS, FS and CFS, CFS and EFS ( P<0.05). The cross validation accuracy of FP, FS, CFS and EFS in predicting the postoperative complication in elderly colorectal cancer patients was 78.7%, 68.6%, 76.3%, and 75.8%, respectively. Conclusions:FP and CFS have moderate predictive performance for postoperative complications in elderly colorectal cancer patients, and there is no difference in predictive performance between the two. Both CFS and FP can be used for the assessment of preoperative frailty in elderly colorectal cancer patients, but considering clinical applicability, CFS is recommended.

Objective:To explore the relationship between red meat intake level and the incidence of stroke in Chinese adults.Methods:The baseline data were from China Chronic Disease Surveillance Project conducted in 60 surveillance sites in 11 provinces in China in 2010. A total of 27 762 subjects with complete data in baseline survey were included in the cohort follow-up from 2016 to 2017. Multivariate nutrient-density cox proportional hazards regression model was used to analyze the association between red meat intake level and the incidence of stroke. Subgroup analysis were performed based on baseline characteristics. Sensitivity analysis was performed by using standard multivariate model, energy partition model and nutrient residual model.Results:In the 26 187 subjects, 1 259 stroke cases, including 1 074 ischemic stroke cases, occurred during an average of 6.0 years of follow-up, the incidence density was 815.0/100 000 person-years for stroke and 692.0/100 000 person-years for ischemic stroke. In models using the multivariate nutrient-density model of energy adjustment, compared with quintile group, red meat intake in quintile 2 group showed no significant association with stroke [hazard ratio ( HR)=1.07, 95% CI: 0.87-1.32] and ischemic stroke ( HR=1.03, 95% CI: 0.80-1.32) and in group of quintile 3-5, the red meat intake related risk for stroke increased by 23% ( HR=1.23, 95% CI: 1.00-1.51), 27% ( HR=1.27, 95% CI: 1.03-1.58) and 32% ( HR=1.32, 95% CI: 1.06-1.64), respectively, while the risk for ischemic stroke increased by 32% ( HR=1.32, 95% CI: 1.04-1.68), 35% ( HR=1.35, 95% CI: 1.05-1.73) and 38% ( HR=1.38, 95% CI: 1.07-1.79), respectively. Subgroup analysis revealed that blood pressure had modification effect on the association between red meat intake and incidence of stroke (interaction P=0.037). The sensitivity analysis showed no changes. Conclusions:These findings suggest that higher intake of red meat is significantly associated with an increased risk for stroke and ischemic stroke. It is necessary to take red meat intake level as one of the important indicators of stroke prevention and control.