Objective To investigate the association between baseline depression and the risk of type 2 diabetes mellitus(T2DM)in middle-aged and elderly people in Chengguan District of Lanzhou.Methods A total of 4471 residents who were followed up in Chengguan District,Lanzhou City from August 2014 to July 2016 in the 2011 REACTION study were selected as the research subjects.According to the 9-item patient health questionnaire(PHQ-9),they were divided into the non-depression group with a score of 0～4 points(ND,n=3827),the mild depression group with a score of 5～10 points(MD,n=546)and the moderate to severe depression group with a score of≥10 points(MSD,n=98).The general data and biochemical indicators of the three groups were compared.The correlation between depression status and glycolipid metabolism indicators was analyzed.The follow-up results of the three groups with different baseline glucose metabolism status populations were compared.Logistic regression was used to analyze the influencing factors of progression in different glucose metabolism populations.Results The married rate in the ND,MD and MSD groups decreased sequentially(P<0.05),while the rate of living alone and the PHQ-9 score increased(P<0.05).The female population,family history of DM,coronary heart disease,LDL-C and TC in the MD group were higher than those in the ND group(P<0.05),while the age,BMI,WHR,FPG and 2 hPG in the MD group were lower than those in the ND group(P<0.05).The family history of DM in the MSD group was higher than those in the ND group(P<0.05),drinking and LDL-C in the MSD group were higher than those in the MD group(P<0.05),the BMI was lower than that in the ND group(P<0.05).Spearman correlation analysis showed that the baseline PHQ-9 score was negatively correlated with FPG level(r=-0.039,P<0.05),and positively correlated with HDL-C and TC(r=0.049,0.031,P<0.05).There was no significant difference in the incidence of pre-DM and T2DM at the end of follow-up among the three groups with different baseline glucose metabolism(P>0.05).Logistic regression analysis showed that after adjusting for confounding factors,the risk of pre-DM and T2DM in normal glucose tolerance people with different depression status and the risk of T2DM in pre-DM patients were not increased.Conclusions Depressive state may not be the main factor affecting the occurrence of T2DM in middle-aged and elderly people in Chengguan District of Lanzhou.

Objective To investigate the association between baseline depression and the risk of type 2 diabetes mellitus(T2DM)in middle-aged and elderly people in Chengguan District of Lanzhou.Methods A total of 4471 residents who were followed up in Chengguan District,Lanzhou City from August 2014 to July 2016 in the 2011 REACTION study were selected as the research subjects.According to the 9-item patient health questionnaire(PHQ-9),they were divided into the non-depression group with a score of 0～4 points(ND,n=3827),the mild depression group with a score of 5～10 points(MD,n=546)and the moderate to severe depression group with a score of≥10 points(MSD,n=98).The general data and biochemical indicators of the three groups were compared.The correlation between depression status and glycolipid metabolism indicators was analyzed.The follow-up results of the three groups with different baseline glucose metabolism status populations were compared.Logistic regression was used to analyze the influencing factors of progression in different glucose metabolism populations.Results The married rate in the ND,MD and MSD groups decreased sequentially(P<0.05),while the rate of living alone and the PHQ-9 score increased(P<0.05).The female population,family history of DM,coronary heart disease,LDL-C and TC in the MD group were higher than those in the ND group(P<0.05),while the age,BMI,WHR,FPG and 2 hPG in the MD group were lower than those in the ND group(P<0.05).The family history of DM in the MSD group was higher than those in the ND group(P<0.05),drinking and LDL-C in the MSD group were higher than those in the MD group(P<0.05),the BMI was lower than that in the ND group(P<0.05).Spearman correlation analysis showed that the baseline PHQ-9 score was negatively correlated with FPG level(r=-0.039,P<0.05),and positively correlated with HDL-C and TC(r=0.049,0.031,P<0.05).There was no significant difference in the incidence of pre-DM and T2DM at the end of follow-up among the three groups with different baseline glucose metabolism(P>0.05).Logistic regression analysis showed that after adjusting for confounding factors,the risk of pre-DM and T2DM in normal glucose tolerance people with different depression status and the risk of T2DM in pre-DM patients were not increased.Conclusions Depressive state may not be the main factor affecting the occurrence of T2DM in middle-aged and elderly people in Chengguan District of Lanzhou.

Objective:To evaluate the structural and functional changes of the left atrium in amateur ultra-marathon runners using ultrasound three-dimensional speckle tracking imaging technology.Methods:From June 2023 to June 2024，90 amateur marathon athletes were retrospectively recruited，including 44 amateur ultra-marathon（running distance ≥50 km）athletes（Ultra-marathon，UM group）and 46 amateur classic marathon（running distance<50 km）athletes（Marathon，M group）. Another 39 healthy volunteers who underwent physical examinations in Hangzhou Normal University Affiliated Hospital at the same time were selected as the control group. The distance，running age of amateur marathon runners were recorded. All subjects which underwent conventional echocardiography combined with three-dimensional speckle tracking echocardiography（3D-STE）obtained left atrial volume and functional parameters，including two-dimensional ultrasound indicators such as left atrial anterior posterior diameter（LAd），left ventricular end-diastolic diameter（LVEDd），left ventricular ejection fraction（LVEF），early diastolic peak velocity at the mitral valve orifice（E），and early diastolic peak velocity at the lateral mitral annulus（e'），E/e'，left atrial minimum，maximum，presystolic volumes（LAVmin，LAVmax，LAVpreA），left atrial maximum volume index（LAVImax），left atrial emptying volume（LAEV），overall left atrial ejection fraction，active and passive ejection fraction（LAEF，LAaEF，LApEF），left atrial expansion index（LAEI），left atrial reservoir period，conduit period，systolic long axis and circumferential strain（LASr，LAScd，LASct，LASr-c，LAScd-c，LASct-c）. The differences in left atrial parameters among three groups were compared and the relevant factors affecting LAEF were analyzed.Results:There were statistically significant differences in LAd，LVEDd，LAVmin，LAVmax，LAVpreA，LAVImax，and LAEV among the three groups（all P<0.05），and there were statistically significant differences in pairwise comparisons between the groups（all P<0.05）. Compared with the control group，LAEF，LApEF，LASr，LAScd，LASct，LASr-c，LAScd-c and LASct-c were significantly reduced in the M and UM groups（all P<0.05），while there were no statistically significant differences in these parameters between the UM and M groups（all P>0.05）；There were no statistically significant differences in IVSd，LVEF，E/e'，LAEI，and LAaEF among the 3 groups（all P>0.05）.There were no statistically significant differences in IVSd，LVEF，E/e'，LAaEF and LAEI among the 3 groups（all P>0.05）. Multiple linear regression analysis showed that only weekly running volume was an independent predictor of decreased LAEF in amateur marathon runners. The repeatability test indicated good consistency within and between observers. Conclusions:Amateur marathon runners have varying degrees of damage to their left atrial reservoir function，conduit function，and contraction function，with amateur ultra-marathon runners showing more significant damages，3D-STE technology can evaluate the structural and functional changes in the left atrium in amateur ultra-marathon athletes，and assist clinical understanding of atrial adaptation in amateur ultra- marathon athletes.

AIM: To identify the primary active components and underlying mechanisms of Yijing Decoction(YJD)in treating early diabetic retinopathy(DR)based on liquid chromatography-mass spectrometry and network pharmacology.METHODS: Active components of YJD were characterized through LC-MS. Components with optimal ADME(absorption, distribution, metabolism, excretion)properties were selected as key bioactive candidates. Network pharmacology approaches were employed to predict YJD-DR therapeutic targets. Protein-protein interaction(PPI)networks, gene ontology(GO)enrichment analysis, and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway analysis were subsequently conducted to predict core targets and networks. Critical targets and pathways were experimentally validated through Western blot.RESULTS: Ten core therapeutic targets were identified, including TNF, Alb, EGFR, STAT3, PTGS2, ESR1, PPAR, MMP9, TLR4, and MAPK. YJD was related to cancer-related signaling, fluid shear stress and atherosclerosis, and neurodegenerative diseases, encompassing key biological processes such as inflammatory response regulation, programmed cell death activation, and enhanced cell migration. Furthermore, Western blot analysis confirmed that YJD significantly inhibited high glucose-induced phosphorylation of STAT3(P-STAT3/STAT3)and ERK(P-ERK/ERK)in rat retinal microvascular endothelial cells.CONCLUSION: This study revealed YJD's pharmacodynamical basis and its multi-component, multi-target, and multi-paths pharmacology. YJD exerts therapeutic effects on DR by coordinately regulating critical signaling pathways and alleviating intraocular inflammation, thus preserving retinal vascular endothelial cells, maintaining blood-retinal barrier integrity, and facilitating retinal neurovascular repair.

Mycophenolic acid (MPA), the active moiety of both mycophenolate mofetil (MMF) and enteric-coated mycophenolate sodium (EC-MPS), serves as a primary immunosuppressant for maintaining solid organ transplants. Therapeutic drug monitoring (TDM) enhances treatment outcomes through tailored approaches. This study aimed to develop an evidence-based guideline for MPA TDM, facilitating its rational application in clinical settings. The guideline plan was drawn from the Institute of Medicine and World Health Organization (WHO) guidelines. Using the Delphi method, clinical questions and outcome indicators were generated. Systematic reviews, Grading of Recommendations Assessment, Development, and Evaluation (GRADE) evidence quality evaluations, expert opinions, and patient values guided evidence-based suggestions for the guideline. External reviews further refined the recommendations. The guideline for the TDM of MPA (IPGRP-2020CN099) consists of four sections and 16 recommendations encompassing target populations, monitoring strategies, dosage regimens, and influencing factors. High-risk populations, timing of TDM, area under the curve (AUC) versus trough concentration (C₀), target concentration ranges, monitoring frequency, and analytical methods are addressed. Formulation-specific recommendations, initial dosage regimens, populations with unique considerations, pharmacokinetic-informed dosing, body weight factors, pharmacogenetics, and drug‍-‍drug interactions are covered. The evidence-based guideline offers a comprehensive recommendation for solid organ transplant recipients undergoing MPA therapy, promoting standardization of MPA TDM, and enhancing treatment efficacy and safety.
Mycophenolic Acid/administration & dosage* ; Drug Monitoring/methods* ; Humans ; Organ Transplantation ; Immunosuppressive Agents/administration & dosage* ; Delphi Technique

Obesity usually exacerbates the immunosuppressive tumor microenvironment (ITME), hindering CD8⁺ T cell infiltration and function, which further represents a significant barrier to the efficacy of immunotherapy. Herein, a multifunctional liposomal system (CR-Lip) for encapsulating celastrol (CEL) was utilized to remodel obesity-related ITME and improve cancer immunotherapy, wherein Ginsenoside Rg3 (Rg3) was detected interspersed in the phospholipid bilayer and its glycosyl exposed on the surface of the liposome. CR-Lip had a relatively uniform size (116.5 nm), facilitating favorable tumor tissue accumulation through the interaction between Rg3 and glucose transporter 1 overexpressed in obese tumor cells. Upon reaching the tumor region, CR-Lip was found to induce the immunogenic cell death (ICD) of HFD tumor cells. Notably, the level of PHD3 in HFD tumor cells was effectively boosted by CR-Lip to effectively block metabolic reprogramming and increase the availability of major free fatty acids fuel sources. In vivo, experiments studies revealed that the easy-obtained nano platform stimulated enhanced the production of various cytokines in tumor tissues, DC maturation, CD8⁺ T-cell infiltration, and synergistic anticancer therapeutic potency with aPD-1 (tumor inhibition rate = 82.1%) towards obesity-related melanoma. Consequently, this study presented an efficacious approach to tumor immunotherapy in obese mice by encompassing tumor eradication, inducing ICD, and reprogramming metabolism. Furthermore, it offered a unique insight into a valuable attempt at the immunotherapy of obesity-associated related tumors.

Colorectal tumorigenesis generally progresses from adenoma to adenocarcinoma, accompanied by dynamic changes in the tumor microenvironment (TME). A randomized controlled trial has confirmed the efficacy and safety of Shen-Bai-Jie-Du decoction (SBJDD) in preventing colorectal tumorigenesis. However, the mechanism remains unclear. In this study, we employed single-cell RNA sequencing (scRNA-seq) to investigate the dynamic evolution of the TME and validated cell infiltration with multiplex immunohistochemistry and flow cytometry. Bulk RNA sequencing was utilized to assess the underlying mechanisms. Our results constructed the mutually verifiable single-cell transcriptomic atlases in Apc ^Min/+ mice and clinical patients. There was a marked accumulation of CCL22⁺ dendritic cells (DCs) and an enhanced immunosuppressive action, which SBJDD and berberine reversed. Combined treatment with cholesterol and lipopolysaccharide induced characteristic gene expression of CCL22⁺ DCs, which may represent "exhausted DCs". Intraperitoneal injection of these DCs after SBJDD treatment eliminated its therapeutic effects. TMEM131 derived CCL22⁺ DCs generation by TNF signaling pathway and may be a potential target of berberine in retarding colorectal tumorigenesis. These findings emphasize the role of exhausted DCs and the regulatory mechanisms of SBJDD and berberine in colorectal cancer (CRC), suggesting that the multi-component properties of SBJDD may help restore TME homeostasis and offer novel cancer therapy.

Objective:To discuss the expression and clinical significance of inositol polyphosphate-4-phosphatase type Ⅱ(INPP4B)gene in hepatocellular carcinoma(HCC)based on The Cancer Genome Atlas(TCGA)database and experimental verification with clinical samples.Methods:Based on data from 424 clinical samples in the TCGA database(including 374 HCC tissues and 50 paracarcinoma tissues),Kaplan-Meier method and Cox regression analysis were used to evaluate the relationship between INPP4B gene and the clinical characteristics and survival prognosis of the HCC patients.The correlations between INPP4B gene and the number of 24 types of immune cells,matrix,immune cell infiltration and tumor purity in tumor tissue,and the expression level of the high-frequency mutant gene tumor protein 53(TP53)in HCC were analyzed.The clinicopathological data and paraffin-embedded tissue sections of 60 HCC patients treated with surgical resection from December 2022 to December 2023 were collected.According to clinical diagnosis,they were divided into poorly differentiated group(HCC-L group),moderately differentiated group(HCC-M group)and well-differentiated group(HCC-H group),with 20 cases in each group;20 patients during the same period who underwent biopsy and were pathologically diagnosed as non-tumor were selected as normal group,and their clinicopathologic data and liver tissue paraffin sections were collected.HE staining was used to observe the pathomorphology of HCC tissue and normal liver tissue of the subjects in various groups;immunohistochemistry method was used to detect the expressions of Ki-67 and INPP4B proteins in the HCC tissue and normal liver tissue of the subjects in various groups.Results:The TCGA database analysis results showed that compared with normal tissue,the expression level of INPP4B mRNA in HCC tissue was significantly increased(P<0.01).Compared with INPP4B low expression group,the overall survival(OS)of the patients in INPP4B high expression group was significantly prolonged(P<0.05).The univariate Cox regression analysis results showed that tumor stage,pathological stage,tumor status and residual tumor had impacts on OS of the HCC patients(P<0.05).The univariate regression analysis results showed that the INPP4B prognostic risk model score ratio was HR=0.781,95％confidence interval(CI):0.552-1.105,P=0.168.The AUC value for the impact of INPP4B on OS of the HCC patients was 0.558,indicating that the INPP4B gene prognostic risk model had certain predictive value in survival prognosis.The INPP4B mRNA expression level was not correlated with TNM stage,stage,patient gender,age,race or body mass index(BMI)(P>0.05).In tumor tissue with high and low INPP4B expression,22 types of immune cells showed statistically significant differences(P<0.05);the INPP4B mRNA expression level was positively correlated with the number of 23 types of immune cells except T helper(Th)17 cells(r>0),among which all Th cells except natural killer(NK)CD56+cells were statistically significant(P<0.01);INPP4B was significantly correlated with matrix(r=0.475),immune cell infiltration(r=0.641)and tumor purity(r=0.599)in tumor tissue(P<0.01).INPP4B was correlated with TP53(r=0.287,P<0.01).The HE staining results showed that clear and complete lobular structure,neatly arranged cells and slight inflammatory cell infiltration were observed in liver tissue of the subjects in normal group;completely destroyed lobular structure,significant hepatocellular steatosis,massive inflammatory cell infiltration,and lesions such as ballooning degeneration and small cell hyperplasia in some cells were observed in HCC tissue of the patients in HCC-L,HCC-M and HCC-H groups,and the lower the HCC differentiation degree,the more severe the tissue destruction;The immunohistochemistry results showed that compared with normal group,the expression levels of Ki-67 protein in HCC tissue of the patients in HCC-L,HCC-M and HCC-H groups were significantly increased(P<0.01),and the lower the differentiation degree of the HCC patients,the higher the Ki-67 positive rate.Brownish-yellow granules evenly distributed in the cells and INPP4B protein was highly expressed in liver tissue of the subjects in normal group;compared with normal group,the expression levels of INPP4B protein in HCC tissue of the patients in HCC-L,HCC-M and HCC-H groups were significantly decreased(P<0.01),and the lower the differentiation degree of the HCC tissue,the lower the INPP4B positive rate.Conclusion:INPP4B is a protective factor for the prognosis of HCC patients;as a new tumor suppressor gene,INPP4B may become a potential target for new drug screening in HCC treatment.

OBJECTIVE To explore the value of ultrasonography in the diagnosis of congenital laryngeal web.METHODS A total of 10 pediatric patients with congenital laryngeal web who were admitted to Beijing Tongren Hospital,Capital Medical University from April 2013 to December 2024 were collected.Among them,there were 5 males and 5 females,with ages ranging from 1 month and 16 days to 16 years old after birth,and a median age of 1 year and 11 months.Clinical manifestations included laryngeal stridor,hoarseness,or weak crying after birth.All patients underwent laryngoscopy and laryngeal ultrasonography.The diagnosis was made by combining ultrasound and laryngoscopy examinations.RESULTS It was confirmed by laryngoscopy and operation:The final diagnosis was glottic laryngeal web in 7 cases and combined glottic-subglottic type in 3 cases.In the transverse ultrasound view,glottic laryngeal web appears as a triangular hypoechoic area at the anterior commissure of the glottis level,with its posterior edge presenting as an arc shape,and the interface with air is hyperechoic.In the sagittal ultrasound view,certain web-like structures appear as a strip of hypoechoic area in the midline behind the thyroid cartilage.The thickness can be measured to determine whether it extends from the glottis to the subglottis.For infans,and for subglottic laryngeal web,it is difficult to show the lesion by ultrasound.CONCLUSION Ultrasonography is helpful in the diagnosis of laryngeal web and can display the thickness of the web in the sagittal plane,providing three-dimensional information for preoperative planning.

Objective:To evaluate the utility of ultrasonographic monitoring of the rectus femoris muscle—specifically, the rates of change in thickness and cross-sectional area (CSA)—in assessing nutritional status and long-term functional outcomes in patients with sepsis.Methods:In this prospective observational study, sepsis patients admitted to the ICU of the Second Affiliated Hospital of Soochow University between October 2023 and October 2024 were classified by nutritional status at discharge using the Global Leadership Initiative on Malnutrition (GLIM) criteria. Differences in serial ultrasound-measured rectus femoris thickness and CSA on days 1, 3, 5, and 7 were compared between malnourished and non-malnourished groups. The predictive value of these ultrasound parameters for malnutrition was analyzed. Functional prognosis was assessed using the Sarcopenia Assessment Scale, Short Physical Performance Battery, and Manual Muscle Testing, with correlations to muscle changes examined.Results:Of the 71 enrolled patients (median age 73.00 [ IQR: 61.00–80.00]; 47.89% female, 52.11% male), those with malnutrition showed significantly greater variation rates in rectus femoris thickness and CSA on days 3, 5, and 7 compared to the non-malnourished group ( P < 0.05). ROC analysis revealed that the day-7 CSA variation rate had the highest predictive value for malnutrition (AUC = 0.817, 95% CI: 0.713-0.930). These muscle variation rates also correlated strongly with conventional nutritional markers such as BMI, albumin, and urea. Similarly, patients with impaired functional outcomes exhibited higher variation rates in muscle parameters on days 3, 5, and 7 ( P < 0.05), with the day-7 CSA variation rate being most predictive of functional prognosis (AUC = 0.749, 95% CI: 0.632-0.867). Conclusions:Ultrasonographic assessment of rectus femoris thickness and CSA variation rates provides a valuable tool for evaluating nutritional status and predicting functional prognosis in sepsis patients, outperforming traditional biomarkers. This method shows promise for guiding individualized nutrition support and rehabilitation strategies to improve long-term outcomes.