Limited validity of Mayo endoscopic subscore in ulcerative colitis with concomitant primary sclerosing cholangitis

BACKGROUND Ulcerative colitis(UC)with concomitant primary sclerosing cholangitis(PSC)represents a distinct disease entity(PSC-UC).Mayo endoscopic subscore(MES)is a standard tool for assessing disease activity in UC but its relevance in PSC-UC remains unclear.AIM To assess the accuracy of MES in UC and PSC-UC patients,we performed histological scoring using Nancy histological index(NHI).METHODS MES was assessed in 30 PSC-UC and 29 UC adult patients during endoscopy.NHI and inflammation were evaluated in biopsies from the cecum,rectum,and terminal ileum.In addition,perinuclear anti-neutrophil cytoplasmic antibodies,fecal calprotectin,body mass index,and other relevant clinical characteristics were collected.RESULTS The median MES and NHI were similar for UC patients(MES grade 2 and NHI grade 2 in the rectum)but were different for PSC-UC patients(MES grade 0 and NHI grade 2 in the cecum).There was a correlation between MES and NHI for UC patients(Spearman's r=0.40,P=0.029)but not for PSC-UC patients.Histopathological examination revealed persistent microscopic inflammation in 88%of PSC-UC patients with MES grade 0(46%of all PSC-UC patients).Moreover,MES overestimated the severity of active inflammation in an additional 11%of PSCUC patients.CONCLUSION MES insufficiently identifies microscopic inflammation in PSC-UC.This indicates that histological evaluation should become a routine procedure of the diagnostic and grading system in both PSC-UC and PSC.

Clinical significance of visceral adiposity assessed by computed tomography: A Japanese perspective

Abdominal obesity,rather than total amount of fat,is linked to obesity-related disorders.Visceral adiposity is an important component of obesity-related disorders in Japanese individuals with a mild degree of adiposity compared with Western subjects.In 1983,our group reported techniques for body fat analysis using computed tomography(CT)and established the concept of visceral fat obesity in which intra-abdominal fat accumulation is an important factor in the development of obesity-related complications,such as diabetes,lipid disorders,hypertension and atherosclerosis.Our group also established ideal imaging conditions for determining abdominal fat area at the umbilical level CT scan.Visceral fat area(VFA)measured in a single slice at L4level correlated significantly with the total abdominal visceral fat volume measured on multislice CT scan.In a large-scale study of a Japanese population,the mean number of obesity-related cardiovascular risk factors(hypertension,low high-density lipoprotein cholesterolemia and/or hypertriglyceridemia,and hyperglycemia)was greater than 1.0 at 100 cm2 of VFA,irrespective of gender,age and body mass index.Our group also demonstrated that reduction of visceral fat accumulation subsequent to voluntary lifestyle modification,"Hokenshido",correlated with a decrease in the number of obesity-related cardiovascular risk factors.It is important to select the most appropriate subjects from the general population(e.g.,non-obese subjects with a cluster of risk factors for the metabolic syndrome)that are most suitable for body weight reduction,with the goal of preventing atherosclerotic cardiovascular diseases.

Post-translational modifications of prostaglandin-endoperoxide synthase 2 in colorectal cancer:An update

The biosynthesis of prostanoids is involved in both physiological and pathological processes. The expression of prostaglandin-endoperoxide synthase 2(PTGS2; also known as COX-2) has been traditionally associated to the onset of several pathologies, from inflammation to cardiovascular, gastrointestinal and oncologic events. For this reason, the search of selective PTGS2 inhibitors has been a focus for therapeutic interventions. In addition to the classic non-steroidal anti-inflammatory drugs, selective and specific PTGS2 inhibitors, termed coxibs, have been generated and widely used. PTGS2 activity is less restrictive in terms of substrate specificity than the homeostatic counterpart PTGS1, and it accounts for the elevated prostanoid synthesis that accompanies several pathologies. The main regulation of PTGS2 occurs at the transcription level. In addition to this, the stability of the mRNA is finely regulated through the interaction with several cytoplasmic elements, ranging from specificmicroR NAs to proteins that control mR NA degradation. Moreover, the protein has been recognized to be the substrate for several post-translational modifications that affect both the enzyme activity and the targeting for degradation via proteasomal and non-proteasomal mechanisms. Among these modifications, phosphorylation, glycosylation and covalent modifications by reactive lipidic intermediates and by free radicals associated to the proinflammatory condition appear to be the main changes. Identification of these post-translational modifications is relevant to better understand the role of PTGS2 in several pathologies and to establish a correct analysis of the potential function of this protein in diseases progress. Finally, these modifications can be used as biomarkers to establish correlations with other parameters, including the immunomodulation dependent on molecular pathological epidemiology determinants, which may provide a better frame for potential therapeutic interventions.

Interplay between post-translational cyclooxygenase-2 modifications and the metabolic and proteomic profile in a colorectal cancer cohort

BACKGROUND Colorectal cancer(CRC) is the second most common cause of cancer death worldwide. It is broadly described that cyclooxygenase-2(COX-2) is mainly overexpressed in CRC but less is known regarding post-translational modifications of this enzyme that may regulate its activity, intracellular localization and stability. Since metabolic and proteomic profile analysis is essential for cancer prognosis and diagnosis, our hypothesis is that the analysis of correlations between these specific parameters and COX-2 state in tumors of a high number of CRC patients could be useful for the understanding of the basis of this cancer in humans.AIM To analyze COX-2 regulation in colorectal cancer and to perform a detailed analysis of their metabolic and proteomic profile.METHODS Biopsies from both healthy and pathological colorectal tissues were taken under informed consent from patients during standard colonoscopy procedure in the University Hospital of Bellvitge(Barcelona, Spain) and Germans Trias i Pujol University Hospital(Campus Can Ruti)(Barcelona, Spain). Western blot analysis was used to determine COX-2 levels. Deglycosylation assays were performed in both cells and tumor samples incubating each sample with peptide N-glycosidase F(PNGase F). Prostaglandin E2(PGE2) levels were determined using a specific ELISA. 1 H high resolution magic angle spinning(HRMAS) analysis was performed using a Bruker AVIII 500 MHz spectrometer and proteomic analysis was performed in a nano-liquid chromatography-tandem mass spectrometer(nano LC-MS/MS) using a QExactive HF orbitrap MS.RESULTS Our data show that COX-2 has a differential expression profile in tumor tissue of CRC patients vs the adjacent non-tumor area, which correspond to a glycosylated and less active state of the protein. This fact was associated to a lesser PGE2 production in tumors. These results were corroborated in vitro performing deglycosylation assays in HT29 cell line where COX-2 protein profile was modified after PNGase F incubation, showing higher PGE2 levels. Moreover,HRMAS analysis indicated that tumor tissue has altered metabolic features vs non-tumor counterparts, presenting increased levels of certain metabolites such as taurine and phosphocholine and lower levels of lactate. In proteomic experiments, we detected an enlarged number of proteins in tumors that are mainly implicated in basic biological functions like mitochondrial activity,DNA/RNA processing, vesicular trafficking, metabolism, cytoskeleton and splicing.CONCLUSION In our colorectal cancer cohort, tumor tissue presents a differential COX-2 expression pattern with lower enzymatic activity that can be related to an altered metabolic and proteomic profile.

Isolated ileal perforation due to cytomegalovirus reactivation during management of terbinafine hypersensitivity

We report a case of 71-year-old man who developed a hypersensitivity syndrome associated with terbinafine. He was placed on terbinafine (250 mg/d) for the treatment of tinea pedis due to diabetes mellitus. Following the treatment with terbinafine, he developed druginduced hypersensitivity syndrome (DIHS). Systemic corticosteroid led to transient improvement of his clinical manifestations. Three months after disease onset, he presented with panperitonitis due to ileal perforation, and underwent an emergency operation. The affected ileum was resected and ileostomy was performed in the terminal ileum. Cytomegalovirus (CMV)-specific IgG antibodies were significantly increased, high-titer CMV antigenemia was detected, and pathological examination of the resected ileum confirmed CMV infection. Based onthese observations, we strongly recommend that physicians monitor reactivation of the family of herpesvirus other than herpesvirus 6, to manage DIHS properly.

Metformin accelerates bone fracture healing by promoting type H vessel formation through inhibition of YAP1/TAZ expression

Due to increasing morbidity worldwide,fractures are becoming an emerging public health concern.This study aimed to investigate the effect of metformin on the healing of osteoporotic as well as normal fractures.Type H vessels have recently been identified as a bone-specific vascular subtype that supports osteogenesis.Here,we show that metformin accelerated fracture healing in both osteoporotic and normal mice.Moreover,metformin promoted angiogenesis in vitro under hypoxia as well as type H vessel formation throughout fracture healing.Mechanistically,metformin increased the expression of HIF-1α,an important positive regulator of type H vessel formation,by inhibiting the expression of YAP1/TAZ in calluses and hypoxia-cultured human microvascular endothelial cells(HMECs).The results of HIF-1αor YAP1/TAZ interference in hypoxia-cultured HMECs using si RNA further suggested that the enhancement of HIF-1αand its target genes by metformin is primarily through YAP1/TAZ inhibition.Finally,overexpression of YAP1/TAZ partially counteracted the effect of metformin in promoting type H vessel-induced angiogenesis-osteogenesis coupling during fracture repair.In summary,our findings suggest that metformin has the potential to be a therapeutic agent for fractures by promoting type H vessel formation through YAP1/TAZ inhibition.

Risk of lymph node metastases in patients with T1b oesophageal adenocarcinoma: A retrospective single centre experience

AIM To assess clinical outcomes for submucosal (T1b) oesophageal adenocarcinoma (OAC) patients managed with either surgery or endoscopic eradication therapy.METHODS Patients found to have T1b OAC following endoscopic resection between January 2008 to February 2016 at University College London Hospital were retrospectively analysed. Patients were split into low-risk and high-risk groups according to established histopathological criteria and were then further categorised according to whether they underwent surgical resection or conservative management. Study outcomes include the presence of lymphnode metastases, disease-specific mortality and overall survival. RESULTS A total of 60 patients were included; 22 patients were surgically managed (1 low-risk and 21 high-risk patients) whilst 38 patients were treated conservatively (12 low-risk and 26 high-risk). Overall, lymph node metastases (LNM) were detected in 10 patients (17%); six of these patients had undergone conservative management and LNM were detected at a median of 4 mo after endoscopic mucosal resection (EMR). All LNM occurred in patients with highrisk lesions and this represented 21% of the total high-risk lesions. Importantly, there was no statistically significant difference in tumor-related deaths between those treated surgically or conservatively (P = 0.636) and disease-specific survival time was also comparable between the two treatment strategies (P = 0.376).CONCLUSION T1b tumours without histopathological high-risk markers of LNM can be treated endoscopically with good outcomes. In selected patients, endoscopic therapy may be appropriate for high-risk lesions.

Sequential elevation of autoantibodies to thyroglobulin and glutamic acid decarboxylase in type 1 diabetes

We have previously reported the high levels of glutamic acid decarboxylase 65 autoantibodies(GAD65A)in patients with type 1 diabetes and autoimmune thyroid disease.Here we describe a 32-year-old Japanese female with a thirteen-year history of type 1 diabetes whose levels of GAD65A were elevated just after the emergence of anti-thyroid autoimmunity.At 19 years of age,she developed diabetic ketoacidosis and was diagnosed with type 1 diabetes.She had GAD65A,insulinoma-associated antigen-2 autoantibodies(IA-2A),and zinc transporter-8 autoantibodies(ZnT8A),but was negative for antibodies to thyroid peroxidase(TPOAb)and thyroglobulin(TGAb)at disease onset.ZnT8A and IA-2A turned negative 2-3 years after the onset,whereas GAD65A were persistently positive at lower level(approximately 40 U/mL).However,just after the emergence of TGAb at disease duration of 12.5 years,GAD65A levels were reelevated up to5717 U/mL in the absence of ZnT8A and IA-2A.Her thyroid function was normal and TPOAb were consistently negative.She has a HLA-DRB1*03:01/*04:01-DQB1*02:01/*03:02 genotype.Persistent positivity for GAD65A might be associated with increased risk to develop anti-thyroid autoimmunity.

Structural changes of proteins in liver cirrhosis and consequential changes in their function

The liver is the site of synthesis of the majority of circulating proteins.Besides initial polypeptide synthesis,sophisticated machinery is involved in the further processing of proteins by removing parts of them and/or adding functional groups and small molecules tailoring the final molecule to suit its physiological purpose.Posttranslational modifications(PTMs)design a network of molecules with the common protein ancestor but with slightly or considerably varying activity/localization/purpose.PTMs can change under pathological conditions,giving rise to aberrant or overmodified proteins.Undesired changes in the structure of proteins most often accompany undesired changes in their function,such as reduced activity or the appearance of new effects.Proper protein processing is essential for the reactions in living beings and crucial for the overall quality control.Modifications that occur on proteins synthesized in the liver whose PTMs are cirrhosis-related are oxidation,nitration,glycosylation,acetylation,and ubiquitination.Some of them predominantly affect proteins that remain in liver cells,whereas others predominantly occur on proteins that leave the liver or originate from other tissues and perform their function in the circulation.Altered PTMs of certain proteins are potential candidates as biomarkers of liver-related diseases,including cirrhosis.This review will focus on PTMs on proteins whose structural changes in cirrhosis exert or are suspected to exert the most serious functional consequences.

Meta-analysis of therapy of Kang’ai injection combined with chemotherapy in the treatment of non-small cell lung cancer

Objective:To compare the safety and efficacy of Kang’ai injection combined with chemotherapy and chemotherapy alone in the treatment of non-small cell lung cancer.Methods:The related control and randomized studies from 1966 to October 01,2022,were retrieved in the following databases:China National Knowledge Infrastructure,Wanfang databases,Value In Paper,SinoMed,PubMed,Embase and Cochrane Library.A comprehensive literature search was conducted in 7 electronic databases identifying all the relevant randomized controlled trials.Cochrane handbook 5.2.3 was applied to evaluate the quality of included trials,and the RevMan 5.3 software was used to analyze data and assess the publication bias.Results:From the 16 studies reviewed,a total of 1,398 patients were included.Compared with docetaxel+cis-platinum chemotherapy alone,Kang’ai injection combined with docetaxel+cis-platinum chemotherapy showed significant effects in improving clinical response rate(RR:1.40,95%confidence interval(CI)(1.25,1.58)),quality of life score(Karnofsky score)(RR:1.53,95%CI(1.32,1.78)),traditional Chinese medicine syndrome(RR:2.01,95%CI(1.43,2.83))and safety(RR:0.62,95%CI(0.54,0.71)),the differences were statistically significant.Conclusion:Kang’ai injection may increase the therapeutic effectiveness,improve the quality of life,and reduce the toxicity of chemotherapy in patients with non-small cell lung cancer.These results require confirmation by further rigorously designed randomized controlled trials(PROSPERO registration number:CRD42020176917).

COX-2 in liver,from regeneration to hepatocarcinogenesis:What we have learned from animal models?

The use of animals lacking genes or expressing genes under the control of cell-specific promoters has signifi cantly increased our knowledge of the genetic and molecular basis of physiopathology,allowing testing of functional hypotheses and validation of biochemical and pharmacologic approaches in order to understand cell function.However,with unexpected frequency,gene knockout animals and,more commonly,animal models of transgenesis give experimental support to even opposite conclusions on gene function.Here we summarize what we learned on the role of cyclooxygenase 2(COX-2) in liver and revise the results obtained in 3 independent models of mice expressing a COX-2 transgene specifi cally in the hepatocyte.Upon challenge with pro-inflammatory stimuli,the animals behave very differently,some transgenic models having a protective effect but others enhancing the injury.In addition,one transgene exerts differential effects on normal liver physiology depending on the transgenic animal model used.

Low serum amylase and obesity, diabetes and metabolic syndrome: A novel interpretation

For the last decade, low serum amylase(hypoamylasemia) has been reported in certain common cardiometabolic conditions such as obesity, diabetes(regardless of type), and metabolic syndrome, all of which appear to have a common etiology of insufficient insulin action due to insulin resistance and/or diminished insulin secretion. Some clinical studies have shown that salivary amylase may be preferentially decreased in obese individuals, whereas others have revealed that pancreatic amylase may be preferentially decreased in diabetic subjects with insulin dependence. Despite this accumulated evidence, the clinical relevance of serum, salivary, and pancreatic amylase and the underlying mechanisms have not been fully elucidated. In recent years, copy number variations(CNVs) in the salivary amylase gene(AMY1), which range more broadly than the pancreatic amylase gene(AMY2A and AMY2B), have been shown to be well correlated with salivary and serum amylase levels. In addition, low CNV of AMY1, indicating low salivary amylase, was associated with insulin resistance, obesity, low taste perception/satiety, and postprandial hyperglycemia through impaired insulin secretion at early cephalic phase. In most populations, insulin-dependent diabetes is less prevalent(minor contribution) compared with insulin-independent diabetes, and obesity is highly prevalent compared with low body weight. Therefore, obesity as a condition that elicits cardiometabolic diseases relating to insulin resistance(major contribution) may be a common determinant for low serum amylase in a general population. In this review, the novel interpretation of low serum, salivary, and pancreas amylase is discussed in terms of major contributions of obesity, diabetes, and metabolic syndrome.

Cyclooxygenase 2 in liver dysfunction and carcinogenesis: Facts and perspectives

The biosynthesis of prostaglandins and thromboxanes has been a focus of interest in the management of many liver diseases.Cyclooxygenases are the enzymes involved in the first step of the biosynthesis of these lipid mediators and selective inhibitors for these isoenzymes as well as pharmacological analogues of prostaglandins have been developed and are currently applied therapeutically.Here we discuss the implications of these enzymes in the onset of metabolic and lipid disorders in the liver and their potential role in the progression of the diseases towards fibrosis and hepatocellular carcinogenesis.

Skeletal phenotypes in secreted frizzled-related protein 4 gene knockout mice mimic skeletal architectural abnormalities in subjects with Pyle's disease from SFRP4 mutations

Mutations in SFRP4 cause Pyle’s bone disease with wide metaphyses and increased skeletal fragility.The WNT signaling pathway plays important roles in determining skeletal architecture and SFRP4 is a secreted Frizzled decoy receptor that inhibits WNT signaling.Seven cohorts of male and female Sfrp4 gene knockout mice,examined through 2 years of age,had a normal lifespan but showed cortical and trabecular bone phenotypes.Mimicking human Erlenmeyer flask deformities,bone cross-sectional areas were elevated 2-fold in the distal femur and proximal tibia but only 30%in femur and tibia shafts.Reduced cortical bone thickness was observed in the vertebral body,midshaft femur and distal tibia.Elevated trabecular bone mass and numbers were observed in the vertebral body,distal femur metaphysis and proximal tibia metaphysis.Midshaft femurs retained extensive trabecular bone through 2 years of age.Vertebral bodies had increased compressive strength,but femur shafts had reduced bending strength.Trabecular,but not cortical,bone parameters in heterozygous Sfrp4mice were modestly affected.Ovariectomy resulted in similar declines in both cortical and trabecular bone mass in wild-type and Sfrp4 KO mice.SFRP4 is critical for metaphyseal bone modeling involved in determining bone width.Sfrp4 KO mice show similar skeletal architecture and bone fragility deficits observed in patients with Pyle’s disease with SFRP4 mutations.

Liver function tests and metabolic-associated fatty liver disease:Changes in upper normal limits,does it really matter?

BACKGROUND Metabolic-associated fatty liver disease(MAFLD)is the commonest cause of abnormal liver function tests(LFTs).Current upper normal of limit(UNL)of LFTs was derived from a“healthy”population,where undiagnosed MAFLD and viral hepatitis might be suspected.AIM To evaluated potential implications of changes in UNL of alanine aminotransferase(ALT)in MAFLD.METHODS We retrospectively assessed consecutive first referrals with a diagnosis of MAFLD from 2010 to 2017.The conventional UNL of ALT was 45 IU/L for men and 34 IU/L for women,while a low UNL of ALT was 30 IU/L for men and 19 IU/L for women.The UNL of aspartate aminotransferase(AST)was 40 IU/L.RESULTS Total 436 patients were enrolled;of these,288 underwent liver biopsy.Setting a lower UNL reduced the percentage of those with significant disease despite normal ALT;specifically,patients with advanced fibrosis(F≥F3)or definite“metabolic-associated steato-hepatitis(MASH)”(NAS≥5)within normal ALT decreased from 10%to 1%and from 28%to 4%respectively.However,the proportion of those with elevated ALT and no evidence of advanced fibrosis or“definite MASH”increased from 39%to 47%and from 3%to 19%.Overall,LFTs performed poorly in distinguishing“definite MASH”from simple steatosis(receiver operating characteristic areas under the curves 0.59 for ALT and 0.55 for AST).CONCLUSION Liver function tests might both under-and overestimate MASH-related liver disease.Reducing the UNL might not be beneficial and imply an increase in healthcare burden.Risk stratification in MAFLD should rely on a combination of risk factors,not on LFTs alone.

Faster Healing Process by Sparing Intramural Myoma’s Pseudocapsule during Laparoscopic Myomectomy Compared with Removing It during Open Myomectomy

Uterine fibroids are the most common benign tumours in the reproductive system. They are proliferations of smooth muscle cells of the myometrium containing a large quantity of extracellular matrix and they are surrounded by a pseudo capsule of compressed areolar tissue and smooth muscle cells. They can cause various symptoms such as menorrhage, pain and infertility and therefore they can be a traumatic experience for several women. The treatment of choice is myomectomy. In the past, myomectomy was performed by relatively atraumatic techniques, which involved stretching the myoma from its pseudocapsule to extract the fibroid directly from the surrounding fibromuscular tissue, breaking up the fibrous bridge. Modern laparoscopic intracapsular myomectomy (LIM), however, leaves the fibrovascular network surrounding the myoma (namely the “fibroid neurovascular bundle”) intact which reduces the bleeding and/or uterine musculature trauma, and spares the neuropeptide fibers of the pseudocapsule. In this observational study, we compare the two techniques-laparoscopic intracapsular myomectomy (LIM) and conventional abdominal myomectomy (CAM) regarding the longterm uterine healing and a significantly faster healing process of the uterine incision was achieved by LIM compared to CAM.

Schistosoma japonicum Eggs Exerts Protective Effects in an Experimental Ulcerative Colitis Model

Ulcerative colitis(UC)is a chronic inflammatory disease affecting the colon,with an increasing incidence worldwide.Disease pathogenesis is multifactorial and involves genetic predisposition,epithelial barrier defects,dysregulated immune responses,and environmental factors[1,2].

On COVID-19 and Membrane Lipids and Public Health

Coronavirus has a lipid membrane.Whist replication requires hijacking the RNA tools of the host to synthesize virion protein,that then has to be wrapped in a lipid membrane to enable the budding off which extends the infection.Recent studies implicate certain essential fatty acids with replication suppression properties.The lipid membrane is commonly thought of as a fatty barrier to water solubles.It is however highly ordered and compositionally specific to cellular and sub cellular functions.There will likely also be an optimum specificity for the viral coat.Whist DNA,RNA and protein compositions are not affected by diet,the lipid membrane is.Moreover,the greater sensitivity of males over females to inadequacy of these essential fatty acids and membrane integrity has been known since the 1960 s.With evidence that arachidonic and docosahexaenoic acids exhibiting anti-viral,immune,anti-inflammatory,blood pressure control and resolvin activity,their status needs to be urgently examined in relation to the prevention and therapy for Covid-19.It would also be advisable to re-assess food policy.The lipid requirements for the membrane rich systems as in the brain,nervous,vascular and immune systems have not been considered.There is little doubt these were significant in shaping the human genome over several million years.Departure from such conditions would be predicted to put populations at risk to disorder and infection,with males being more at risk than females.

Individualized coefficient of variability cut-off values for reducing the risk of hypoglycemia in Chinese type 1 diabetes mellitus(T1DM)patients

To the Editor:Type 1 diabetes mellitus(T1DM)is a progressive disease caused by severe islet b-cell function impairment,resulting in high glucose variability(GV)in patients.[1]While intensive insulin treatment enabled T1DM patients to achieve near-normal glucose,reflected by reduced hemoglobin A1c(HbA1c)levels,stricter HbA1c targets were associated with an increased risk of hypoglycemia,which would compromise patients’quality of life and survival.[2]Recent studies suggest that GV reflects hypoglycemia better than HbA1c alone,and continuous glucose monitoring(CGM)provides a more comprehensive glycemic profile for better glucose indices assessment.[3]Therefore,we aimed to explore the relationship between the coefficient of variability(CV)of blood glucose and hypoglycemia in T1DM patients with different HbA1c levels and to identify the optimal cut-off values of CV for reducing the hypoglycemia risk in Chinese T1DM patients.

Implications of glycemic risk index across different levels of glycated hemoglobin(HbA1c)in type 1 diabetes

To the Editor:Glycemic control in individuals with type 1 diabetes(T1D)is challenging and requires multidimensional evaluation and precise management.Glycated hemoglobin(HbA1c)is currently the gold standard for assessing glucose control and predicting diabetes prognosis.However,it exhibits limitations in terms of accuracy,which is influenced by clinical factors,^([1])and its inability to reflect information about hypoglycemia and glycemic variability.[2]Continuous glucose monitoring(CGM)has revolutionized glycemic profile evaluation by introducing novel glycemic variables that surpass conventional parameters and offer insights into critical areas for improving glycemic control.