This article presents a case study of a patient who visited the Geriatric Department of Peking Union Medical College Hospital due to "palpitations, shortness of breath for more than 2 years, limb weakness for 6 months, edema, and nocturnal dyspnea for 2 months". The patient exhibited decreased muscle strength in the limbs and involvement of swallowing and respiratory muscles, alongside complications of heart failure and various arrhythmias which were predominantly atrial. Laboratory tests revealed the presence of multiple autoantibodies and notably anti-mitochondrial antibodies. Following a comprehensive multidisciplinary evaluation, the patient was diagnosed with anti-mitochondrial antibody-associated inflammatory myopathy. Treatment involved a combination of glucocorticoids and immunosuppressants, along with resistance exercises for muscle strength and rehabilitation training for lung function, resulting in significant improvement of clinical symptoms. The case underscores the importance of collaborative multidisciplinary approaches in diagnosing and treating rare diseases in elderly patients, where careful consideration of clinical manifestations and subtle abnormal clinical data can lead to effective interventions.

OBJECTIVE To explore the main factors influencing the blood concentration of duloxetine， and provide a scientific basis for the individualized use of duloxetine. METHODS Retrospective analysis was conducted on 434 inpatients with depressive disorders at the First Hospital of Hebei Medical University， who were treated with duloxetine and underwent blood concentration monitoring between January 2022 and April 2024. The study examined the impact of various factors， including gender， age， body mass index （BMI）， gene phenotypes， combined medication， drug type （original/generic）， and genotyping results of gene single nucleotide polymorphism loci， on blood concentration and the concentration-to-dose （C/D） after dose adjustment. RESULTS The blood concentration of duloxetine was 76.65 （45.57， 130.31） ng/mL， and C/D was 0.96 （0.63， 1.60） ng·d/（mL·mg）. The blood concentration of duloxetine was positively correlated with the daily dose of administration （R2＝0.253 7， P＜0.001）. Blood concentration of duloxetine in 38.94% of patients exceeded the recommended range specified in the guidelines. Gender， age， BMI， combined use of CYP2D6 enzyme inhibitors， and CYP2D6 and CYP1A2 phenotypes had significant effects on C/D of duloxetine （P＜0.05）. CONCLUSIONS The patient’s age， gender， BMI， combined medication， and genetic phenotypes are closely related to the blood concentration of duloxetine.

Objective To evaluate the performance of the artificial intelligence (AI)-enabled snail identification system for recognition of Oncomelania hupensis robertsoni and Tricula in schistosomiasis-endemic areas of Yunnan Province. Methods Fifty O. hupensis robertsoni and 50 Tricula samples were collected from Yongbei Township, Yongsheng County, Lijiang City, a schistosomiasis-endemic area in Yunnan Province in May 2024. A total of 100 snail sample images were captured with smartphones, including front-view images of 25 O. hupensis robertsoni and 25 Tricula samples (upward shell opening) and back-view images of 25 O. hupensis robertsoni and 25 Tricula samples (downward shell opening). Snail samples were identified as O. hupensis robertsoni or Tricula by schistosomiasis control experts with a deputy senior professional title and above according to image quality and morphological characteristics. A standard dataset for snail image classification was created, and served as a gold standard for recognition of snail samples. A total of 100 snail sample images were recognized with the AI-enabled intelligent snail identification system based on a WeChat mini program in smartphones. Schistosomiasis control professionals were randomly sampled from stations of schistosomisis prevention and control and centers for disease control and prevention in 18 schistosomiasis-endemic counties (districts, cities) of Yunnan Province, for artificial identification of 100 snail sample images. All professionals are assigned to two groups according the median years of snail survey experiences, and the effect of years of snail survey experiences on O. hupensis robertsoni sample image recognition was evaluated. A receiver operating characteristic (ROC) curve was plotted, and the sensitivity, specificity, accuracy, Youden’s index and the area under the curve (AUC) of the AI-enabled intelligent snail identification system and artificial identification were calculated for recognition of snail sample images. The snail sample image recognition results of AI-enabled intelligent snail identification system and artificial identification were compared with the gold standard, and the internal consistency of artificial identification results was evaluated with the Cronbach’s coefficient alpha. Results A total of 54 schistosomiasis control professionals were sampled for artificial identification of snail sample image recognition, with a response rate of 100% (54/54), and the accuracy, sensitivity, specificity, Youden’s index, and AUC of artificial identification were 90%, 86%, 94%, 0.80 and 0.90 for recognition of snail sample images, respectively. The overall Cronbach’s coefficient alpha of artificial identification was 0.768 for recognition of snail sample images, and the Cronbach’s coefficient alpha was 0.916 for recognition of O. hupensis robertsoni snail sample images and 0.925 for recognition of Tricula snail sample images. The overall accuracy of artificial identification was 90% for recognition of snail sample images, and there was no significant difference in the accuracy of artificial identification for recognition of O. hupensis robertsoni (86%) and Tricula snail sample images (94%) (χ² = 1.778, P > 0.05). There was no significant difference in the accuracy of artificial identification for recognition of snail sample images with upward (88%) and downward shell openings (92%) (χ² = 0.444, P > 0.05), and there was a significant difference in the accuracy of artificial identification for recognition of snail sample images between schistosomiasis control professionals with snail survey experiences of 6 years and less (75%) and more than 6 years (90%) (χ² = 7.792, P < 0.05). The accuracy, sensitivity, specificity and AUC of the AI-enabled intelligent snail identification system were 88%, 100%, 76% and 0.88 for recognition of O. hupensis robertsoni snail sample images, and there was no significant difference in the accuracy of recognition of O. hupensis robertsoni snail sample images between the AI-enabled intelligent snail identification system and artificial identification (χ² = 0.204, P > 0.05). In addition, there was no significant difference in the accuracy of artificial identification for recognition of snail sample images with upward (90%) and downward shell openings (86%) (χ² = 0.379, P > 0.05), and there was a significant difference in the accuracy of artificial identification for recognition of snail sample images between schistosomiasis control professionals with snail survey experiences of 6 years and less and more than 6 years (χ² = 5.604, P_adjusted < 0.025). Conclusions The accuracy of recognition of snail sample images is comparable between the AI-enabled intelligent snail identification system and artificial identification by schistosomiasis control professionals, and the AI-enabled intelligent snail identification system is feasible for recognition of O. hupensis robertsoni and Tricula in Yunnan Province.

Periodontitis and diabetes have a close bidirectional relationship that is mutually exacerbated through mechanisms including inflammatory factor interplay and metabolic dysregulation. Research has shown that non-surgical periodontal therapy (NSPT), focused on scaling and root planing (SRP), effectively treats periodontitis, enhances glycemic control, and ameliorates systemic inflammation in diabetic patients. This review summarizes the glycemic improvement effects of diverse NSPT modalities (including SRP alone, SRP with adjunctive antimicrobials, and SRP with laser therapy) on patients with diabetes and periodontitis. SRP significantly reduces hemoglobin A1c (HbA1c) levels, while adjunctive antimicrobials and laser therapy considerably potentiate the glucose-lowering efficacy of SRP. Furthermore, we focus on elucidating the underlying regulatory mechanisms for NSPT-mediated glycemic control improvement, encompassing inflammation factor-mediated JNK/IKKβ pathway activation inducing insulin resistance; advanced glycation end products (AGEs)-triggered RAGE-ROS/NF-κB pathway dysregulation leading to pancreatic β-cell dysfunction; gut microbiota dysbiosis-driven TLR4-MyD88/TRIF signaling axis causing insulin resistance; flagellin from periodontal pathogens impairing insulin secretion; and lipopolysaccharide (LPS) of periodontal pathogens disrupting Th17/Treg balance with downstream STAT3/SOCS3 pathway inhibiting insulin signaling. These insights aim to provide novel references for targeted interventions and synergistic management of diabetes with periodontitis. Although current studies reveal potential benefits and partial mechanisms of NSPT, the following problems remain: unelucidated specific effector molecules and pathway networks for glycemic regulation by different NSPT regimens, significant interindividual variability in treatment response, and undetermined long-term stability of adjunctive therapy benefits. Future research should explore combined therapeutic strategies for synergistic efficacy, mechanistically dissect regulatory pathways, identify key targets, and advance precision management of diabetes-periodontitis comorbidities.

[This corrects the article DOI: 10.1016/j.apsb.2022.05.019.].

Breast cancer is the most common cancer in women and one of the deadliest cancers worldwide.According to the distribution of tumor tissue,breast cancer can be divided into invasive and non-invasive forms.The cancer cells in invasive breast cancer pass through the breast and through the immune system or systemic circulation to different parts of the body,forming metastatic breast cancer.Drug resistance and distant metastasis are the main causes of death from breast cancer.Research on breast cancer has attracted extensive attention from researchers.In vitro construction of tumor models by tissue engineering methods is a common tool for studying cancer mechanisms and anticancer drug screening.The tumor microenvironment consists of cancer cells and various types of stromal cells,including fibroblasts,endothelial cells,mesenchymal cells,and immune cells embedded in the extracellular matrix.The extracellular matrix contains fibrin proteins(such as types Ⅰ,Ⅱ,Ⅲ,Ⅳ,Ⅵ,and Ⅹcollagen and elastin)and glycoproteins(such as proteoglycan,laminin,and fibronectin),which are involved in cell signaling and binding of growth factors.The current traditional two-dimensional(2D)tumor models are limited by the growth environment and often cannot accurately reproduce the heterogeneity and complexity of tumor tissues in vivo.Therefore,in recent years,research on three-dimensional(3D)tumor models has gradually increased,especially 3D bioprinting models with high precision and repeatability.Compared with a 2D model,the 3D environment can better simulate the complex extracellular matrix components and structures in the tumor microenvironment.Three-dimensional models are often used as a bridge between 2D cellular level experiments and animal experiments.Acellular matrix,gelatin,sodium alginate,and other natural materials are widely used in the construction of tumor models because of their excellent biocompatibility and non-immune rejection.Here,we review various natural scaffold materials and construction methods involved in 3D tissue-engineered tumor models,as a reference for research in the field of breast cancer.

Objective To investigate the effect and mechanism of quercetin (QUE)in improving lipid accumulation in hepatocytes by regulating lipolysis and lipophagy pathway.Methods The human hepatocyte cell line 5 (HHL-5)was induced by palmitic acid (PA)to establish a steatogenic hepatocyte model.Quercetin at different concentrations (5,10,20 and 40 μmol/L)has been utilized to interfere with HHL-5 cells for 24 h,and the experiment was divided into six groups:control group,PA group,PA+QUE5 group,PA+QUE10 group,PA+QUE20 groupand PA+QUE40 group.In order to determine the influence of lipophagy on QUE effect,3-methyladenine (3-MA)was used to block autophagy,and HHL-5 cells were divided into the control,PA,PA+QUE40,3-MA,PA+3-MA and PA+3-MA+QUE40 groups.The contents of triglyceride (TG),accumulations of lipid droplets,expression of lipolysis and lipophagy related molecules,and degree of co-localization,and expression level of substrate of autophagy P62 were detected in above 2 types of experimental groups.Results Compared with the control group,the TG content and the lipid accumulation were significantly increased,the protein levels,average fluorescence intensities and colocalization degree of lipolysis related molecules adipose triglycerides lipase(ATGL)and comparative gene identification-58(CGI58),and lipophagy related molecules Ras-related protein 7(RAB7)and microtubule-associated protein 1 light chain 3 beta (LC3β)were significantly decreased,while the expression of P62 was enhanced in HHL-5 cells in the PA group (all P<0.05 ).Compared with the PA group,the triglyceride content and the degree of lipid accumulation in the PA+QUE40 group were significantly decreased,and the protein expression level,average fluorescence intensity and co-localization degree of lipolysis and lipophagy related molecules were significantly increased,while P62 was significantly decreased (P<0.05).When 3-MA was added to the steatogenic hepatocytes to inhibit autophagy,the improvement effect of QUE on lipid accumulation and the regulation of lipolysis and liphagy related molecules in steatogenic hepatocytes were neutralized.Conclusion QUE alleviates lipid accumulation in HHL-5 cells by promoting the expression and interaction of molecules related to lipolysis and lipophagy pathways.However,these effects can be weakened by the autophagy inhibitor 3-MA.

Objective To discuss the clinical application value of super selective renal artery embolization-assisted(SRAE-assisted)laparoscopic partial nephrectomy(LPN).Methods A retrospective analysis of the clinical data of patients with stage T1 renal carcinoma,who received LPN,was conducted.The patients were divided into SRAE group(performing LPN without adopting renal hilum vascular clamping)and VC group(performing LPN with adopting renal hilum vascular clamping).The time spent for operation,amount of intraoperative blood loss,and preoperative and postoperative renal functions were compared between the two groups.According to the warm ischemia time(WIT),the patients of the VC group were subdivided into WIT＜25 min subgroup and WIT≥25 min subgroup,and the preoperative and postoperative renal functions were compared between the two subgroups.Results A total of 59 patients with renal carcinoma were enrolled in this study,including 12 patients in SRAE group and 47 patients in VC group.In VC group,WIT＜25 min subgroup had 33 patients and WIT≥25 min subgroup had 14 patients.In both SRAE group and VC group,no patient was referred to open surgery or total nephrectomy.No patient in SRAE group was referred to traditional LPN.The time spent for operation in SRAE group and VC group was 100.50(73.75,132.50)min and 120.00(90.00,145.00)min respectively,the difference between the two groups was not statistically significant(P＞0.05).The postoperative estimated glomerular filtration rate(eGFR)in SRAE group was 100.56(82.85,106.81),which was remarkably higher than 84.66(70.84,94.85)in VC group(P＜0.05).The postoperative serum creatinine level in VC group was 90.50(77.10,104.90)μmol/L,which was strikingly higher than 72.24(65.97,80.27)μmol/L in SRAE group(P＜0.05).The amount of intraoperative blood loss in SRAE group was 50(50,50)mL,which was lower than 50(50,100)mL in VC group(P＜0.05).In VC group,the postoperative eGFR in WIT≥25 min subgroup was 66.13(47.08,82.50),which was lower than 90.80(77.18,98.78)in WIT＜25 min subgroup(P＜0.05).During the postoperative one-year follow-up,no recurrence was observed in both groups.Conclusion Compared with traditional LPN,SRAE-assisted LPN doesn't need to obstruct the renal hilus during surgery,which can avoid the ischemic impairment of the residual renal function and reduce the amount of intraoperative blood loss,moreover,it doesn't increase the operation time,doesn't increase the incidence of complications such as postoperative bleeding,etc.and doesn't affect the curative efficacy and patient's prognosis.

Objective To analyze the pharmacodynamic interaction of esketamine and propofol in hysteroscopic surgery by response surface method.Methods Forty-five patients underwent elective hystero-scopic surgery,aged 18.5-64.0 years,BMI 18.5-28.0 kg/m2,ASA physical status Ⅰ or Ⅱ.Compound propofol target control infusion of esketamine(0,0.1,0.2,0.3,0.4,0.5,0.6,0.7,and 0.8 μg/ml)with different plasma drug concentrations were selected to keep the plasma drug concentration of esketamine unchanged,and the plasma drug concentration of propofol was increased step by step.To evaluate body re-sponse caused by dilation of the cervix.A response surface model was used to analyze the pharmacodynamic interaction of esketamine and propofol.Results The three-dimensional response surface of esketamine(0.0-0.8 μg/ml)and propofol(1.0-7.0 μg/ml)showed that the two have an additive effect in sedation and inhibition of body activity reaction caused by dilated cervix.The median effective concentration(EC50)of esketamine was 0.61 μg/ml(95％CI 0.41-0.81 μg/ml),and the EC50 of propofol was 4.69 μg/ml(95％CI 3.17-6.21 μg/ml)when inhibits the body activity reaction caused by dilated cervix.Conclusion Response surface method can qualitatively and quantitatively analyze the pharmacodynamic interaction of es-ketamine and propofol.Esketamine and propofol have additive effects in inhibiting the body activity reaction caused by dilated cervix.

BACKGROUND:The structure,physical and chemical properties(such as rheological properties)and biological activity of hyaluronic acid with different molecular weights are quite different.When the degradation degree of non-cross-linked hyaluronic acid is too large and the high-molecular-weight hyaluronic acid is degraded to low-molecular-weight hyaluronic acid,the properties and biological functions of the product will also change,which will affect the use of the product. OBJECTIVE:To review the mechanism of molecular weight degradation of non-cross-linked hyaluronic acid and the impacts of molecular weight degradation on the structure,rheological properties,biological activity and applications of non-cross-linked hyaluronic acid. METHODS:The first author searched the articles related to the molecular weight of hyaluronic acid collected in PubMed,CNKI database and other databases.The high-quality articles with high correlation were screened according to the inclusion and exclusion criteria.The search time was from January 2017 to December 2022.The Chinese and English search terms were"hyaluronic acid,non-cross-linked hyaluronic acid,molecular weight,degradation,structure,rheological properties,biologic activity".Finally,47 articles were included for review and analysis. RESULTS AND CONCLUSION:(1)The molecular weight of non-cross-linked hyaluronic acid is mainly degraded by specific enzymatic hydrolysis and non-specific free radical degradation.(2)The molecular weight degradation of non-cross-linked hyaluronic acid will change its structure and rheological properties,resulting in the untie of polymer network structure,the decrease of rheological properties such as viscosity and viscoelasticity,and the decrease of mechanical properties,which will eventually affect the practical application effect of the product.(3)The biological activity of non-cross-linked hyaluronic acid is molecular weight dependent,and the biological activity of different molecular weight hyaluronic acid is different.Even the same receptor combined with high-molecular-weight hyaluronic acid and low-molecular-weight hyaluronic acid will express completely opposite biological effects.(4)The degradation of molecular weights of non-cross-linked hyaluronic acid will reduce the safety and efficacy of the products,affect their service life and application performance,and ultimately influence the clinical application results.(5)Non-cross-linked hyaluronic acid has great potential as a biodegradable biomaterial in wound healing,tissue engineering,aesthetic medicine and other fields,and further research and understanding of the correlation between molecular weight degradation of non-cross-linked hyaluronic acid and bioactivity is a prerequisite for better development of wound dressings,drug delivery systems and tissue-engineered scaffolds.(6)However,there are currently few studies on the molecular weight degradation of non-cross-linked hyaluronic acid,and it is unclear how to effectively avoid the potential risks associated with the molecular weight degradation of non-cross-linked hyaluronic acid in clinical applications.(7)Therefore,a series of potential risks associated with the molecular weight degradation of non-cross-linked hyaluronic acid during its application,including the effects on its structure,properties and biological activity,and the resulting changes on the body,is one of the future directions that need to be closely investigated.