Metabolic associated fatty liver disease （MAFLD） is the most prevalent chronic liver disease worldwide， and its progression is closely associated with the development of liver fibrosis， liver cirrhosis， and even hepatocellular carcinoma. However， there is still a lack of effective therapies for MAFLD in clinical practice. Telomere is the protective structure at the end of chromosomes， and telomere shortening and functional impairment have been identified as one of the key factors regulating the pathological progression of MAFLD. This article systematically reviews the core mechanism of action of telomere regulation in MAFLD， including its molecular functions in nucleotide metabolism， oxidative stress， and epigenetic regulation， as well as its pathological effect in hepatocytes and hepatic stellate cells. In addition， this article explores the clinical prospects of telomeres as biomarkers and therapeutic targets for MAFLD， in order to provide a theoretical reference for improving the precise diagnosis and treatment system of MAFLD.

Objective:To prepare 89Zr-labeled anti-human podoplanin (PDPN) monoclonal antibody SZ168 and evaluate its feasibility for melanoma immunoPET imaging. Methods:89Zr-desferrioxamine (DFO)-SZ168 was prepared by conjugating p-isothiocyanatobenzyl (SCN-Bn)-DFO with SZ168 and chelating with 89Zr. Quality control analyses were conducted, including labeling rate, radiochemical purity, and in vitro stability. Melanoma mouse models were created, with experimental group ( n=3) and control group ( n=3) receiving tail vein injections of 89Zr-DFO-SZ168 and 89Zr-DFO-immunoglobulin (Ig)G solutions (3.7MBq) respectively. The experimental group underwent microPET/CT imaging at 12, 24, 48 and 72h post-injection, while the control group underwent imaging at 48h post-injection. Tumor and organ radioactivity uptake was analyzed using the ROI method. Mice were sacrificed at 7d post-injection to assess the ex vivo biodistribution of 89Zr-DFO-SZ168 and 89Zr-DFO-IgG. Independent-sample t test was used to analyze the data. Results:The pH value of the 89Zr-DFO-SZ168 solution was approximately 7.0, with a labeling rate >60%, radiochemical purity >95% after PD10 column purification, and good stability after 72h in vitro. Series microPET/CT imagings showed significant tumor visualization in tumor-bearing mice. Radioactivity uptake in tumors peaked at 48h post-injection, while the tumor was not clearly detected by 89Zr-DFO-IgG microPET/CT imaging. Ex vivo biodistribution indicated that 89Zr-DFO-SZ168 mainly accumulated in tumors, liver, and bones, with tumor uptake significantly higher than that of 89Zr-DFO-IgG ((29.36±7.29) percentage activity of injection dose per gram of tissue (%ID/g) vs (8.78±1.63) %ID/g; t=4.77, P=0.009). Immunohistochemistry of tumor specimens showed high expression of PDPN in tumor tissues. Conclusions:The probe 89Zr-DFO-SZ168 is successfully prepared, showing potential for specific molecular imaging diagnosis of melanoma. This lays a basis for developing PDPN molecular target-based immuno-PET diagnosis and integrated diagnosis and treatment for melanoma.

Body weight abnormalities, including overweight, obesity, and underweight, have become a dual public health challenge in Chinese adults: overweight and obesity lead to a variety of chronic complications, while underweight increases the risks of malnutrition, sarcopenia, and organ dysfunction. To systematically address these issues, multidisciplinary experts in endocrinology, sports science, nutrition, and psychiatry from various regions have held multiple weight management seminars. Based on the latest epidemiological data and clinical evidence, they expanded the guideline to include assessment and intervention strategies for underweight, in addition to the core content of obesity management. This guideline outlines the etiological mechanisms, evaluation methods, and multidimensional management strategies for overweight and obesity, covering key areas such as diagnosis and assessment, medical nutrition therapy, exercise prescription, pharmacological intervention, and psychological support. It is intended to provide a scientific and standardized approach to weight management across the adult population, aiming to curb the rising prevalence of obesity, mitigate complications associated with abnormal body weight, and improve nutritional status and overall quality of life.

Objective To evaluate the efficacy and safety of enteric-coated metformin hydrochloride capsules(Junlida?)in patients with T2DM and poor glycemic control under lifestyle interventions.Methods In this study,419 patients with T2DM were recruited from 15 research centers from July 2020 to March 2022,and randomly divided into observation(Obs)group(n=209)and control group(Con,n=210)using a multicenter,randomized,double-blind,non-inferiority trial design.Patients in the Obs group were treated with enteric-coated Metformin hydrochloride capsules(Junlida?),and patients in the Con group were treated with Metformin hydrochloride tablets(Glucophage?).The optimal effective dose of 2 g/d was achieved within 4 weeks,and the reasonable dose was maintained until the end of treatment.The treatment period was 24 weeks.HbA1c and its compliance rate,FPG,and body weight were compared between the two groups in full analysis set(FAS)and protocol set(PPS).Safety and adverse events(AE)were evaluated in safety set(SS).Results A total of 414 participants were randomized(207 cases in Obs group and 207 cases in Con group).414 cases in FAS population(207 cases in Obs group and 207 cases in Con group),and 328 cases in PPS population(164 cases in Obs group and 164 cases in Con group),and 414 cases in SS population(207 cases in Obs group and 207 cases in Con group).After treatment,HbA1c,FPG and body weight were lower in both groups(P<0.05)in FAS and PPS.HbA1c compliance rate was not significantly different between the two groups in FAS and PPS(P>0.05).The results of non-inferiority test showed that the lower limit was>-0.4%in both FAS(-0.154,95%CI-0.384～0.069)and PPS(-0.139,95%CI-0.390～0.112),and the Obs group reached non-inferiority end point.The achievement rate,compliance rate,safety index and incidence of AE were not significantly different between the two groups(P>0.05).Conclusions Junlida? demonstrated non-inferiority to Glucophage? in glycemic control and can be safely and effectively used in patients with diabetes.

Objective:To explore the safety and efficacy of computed tomography (CT) guided percutaneous interstitial brachytherapy in the treatment of recurrent cervical cancer with isolated lesions in the radiated field.Methods:A retrospective analysis was conducted on the clinical data of 30 patients with recurrent cervical cancer with isolated lesions in the radiated field who underwent CT guided percutaneous interstitial implantation for close range radiation treatment at Zhengzhou University Affiliated Cancer Hospital from March 2023 to August 2024. Under local anesthesia, a needle was implanted into the recurrent tumor in the pelvic or abdominal wall of the patients percutaneously guided by CT. The target area was delineated to ensure full dose coverage. The prescribed dose for high-risk clinical target areas was 600 cGy/time, once a week, followed by close range radiotherapy. The number of implanted needles were recorded, and the target area, radiation dose, and other parameters were evaluated through dose volume parameter maps. The degree of lesion shrinkage and the occurrence of complications during and after treatment were observed.Results:30 patients underwent a total of 72 rounds of brachytherapy with implantation, with a technical success rate of 100% (72/72). 20 cases received 2 treatments, 8 cases received 3 treatments, and 2 cases received 4 treatments; 4 cases used 1needle, 20 cases used 2 needles, 4 cases used 3 needles, and 2 cases used 4 needles. The high-risk clinical target dose D 90 was (718.17±222.61) cGy. The average dose D 2cc of 2 cm 3 surrounding the bladder, rectum, sigmoid colon, and small intestine was (168.29±53.80) cGy, (178.87±105.38) cGy, (136.05±78.06) cGy, and (288.91±117.49) cGy, respectively. The median follow-up time was 11 months. Among the 30 patients, there were 12 cases of complete remission,14 cases of partial remission, 3 cases of stable disease, and 1 case of disease progression, with an objective remission rate of 86.7%. None of the patients experienced significant bleeding or pain during treatment. After treatment, 3 patients with recurrent lymph nodes near the rectum developed grade 1 radiation proctitis, which was remitted after treatment. No significant complications were observed in the remaining patients. Conclusion:CT guided percutaneous brachytherapy is safe and feasible for the recurrence of single lesions in the radiated field of cervical cancer.

Objective:To examine the interaction between interpersonal issues and eating behavior problems among college freshmen, and to identify core psychological factors and potential pathways that drive eating behavior.Methods:In October 2019, a total of 5 073 college freshmen from a university in Shanghai were recruited as participants. Their general demographic data were collected, and they were evaluated using the eating disorder examination questionnaire 6.0 (EDE-Q 6.0) and inventory of interpersonal problems-32(IIP-32).Descriptive analyses were performed using SPSS 24.0 software.A regularized partial correlation network was constructed using the graphical least absolute shrinkage and selection operator (GLASSO) in R(v4.2.3) software. A Bayesian network analysis (BNA) was conducted to build a directed network, aiming to identify core driving factors and key psychological mechanisms.Results:Regularized partial correlation network identified shape concern as the most central node, with the highest strength centrality(1.32) and expected influence(1.20). It showed the highest bridge strength with dominance/control (0.22, 0.21), linking the interpersonal and eating behavior modules. Directed network analysis indicated that low self-confidence was the upstream node influencing social inhibition and cold/ distant relationships, indirectly affecting eating disorder.Within the eating module, shape concern and weight concern predicted eating preoccupation and dietary restraint, forming a pathway structure from eating cognition to behavior.The network demonstrated good stability (CS-coefficient=0.75).Conclusion:Shape concern is the core mechanism underlying eating problems in college freshmen. Low self-confidence contributes indirectly via interpersonal dysfunction. Dominance/control and shape concern bridge interpersonal and eating domains, providing key targets for early prevention and intervention.

The incidence of generalized anxiety disorder(GAD)has recently been increasing year by year,in a complex social environment.The diagnosis of GAD currently often relies on DSM-5 and ICD-10 criteria,which include subjectivity and limitations.Understanding the intrinsic activity of brain network functions and structural connectivity is an important goal of contemporary neuroscience research.Electroencephalographic microstates are capable of observing broad frequency components and capturing dynamic changes in brain activity,thus providing a novel perspective on the accuracy of GAD diagnosis.This review considers the electroencephalographic microstate features and explores the abnormalities in the functional brain network in patients with GAD,with the aim of providing a clear diagnosis,optimizing the therapeutic efficacy,and improving the quality of medical care for patients with GAD.

Corneal endothelial decompensation is a condition caused by a decline in corneal endothelial cells (CECs) density below a critical threshold, leading to corneal edema, clouding, and impaired vision.CECs have minimal regenerative capacity in the human body and gradually decrease in number with age.When affected by pathological factors such as inflammation, trauma or infection, irreversible damage can occur.Traditional treatments include penetrating keratoplasty and posterior lamellar endothelial keratoplasty.However, their application in clinical practice is limited due to problems such as donor shortage, postoperative complications and technical challenge.In recent years, with advances in the understanding of CECs biology and corneal transplantation techniques, emerging approaches such as cell therapy (including cell injection and tissue-engineered endothelial grafts), pharmacological interventions (such as ROCK inhibitors and anti-oxidative stress drugs), and gene therapy (such as CRISPR/Cas9 and RNA interference) have been developed.This review summarizes both traditional and emerging treatments for corneal endothelial decompensation, comparing their advantages and limitations in terms of surgical method, cell source, pharmatheutical therapy, and gene-targeting strategy, and discusses future development trends to provide theoretical support for clinical treatment and research.

Objective:Analyze the risk factors of gastrointestinal perforation caused by foreign body and summarize the experience of surgical treatment of foreign bodies.Method:From Jan 2008 to Dec 2023, 89 patients with foreign bodies in the digestive tract were admitted to the Department of Gastrointestinal Surgery, Peking University First Hospital. Relevant data were collected and binary logistic regression was used to analyze the independent risk factors for intestinal perforation, resection and anastomosis of intestine or enterostomy/colostomy.Results:The mean age of 89 patients was (60.1±16.2) years old, 65 patients (73%) had unintentionally ingested foreign bodies. The most common foreign bodies were jujube pits (40 cases). Thirty-nine patients diagnosed with gastrointestinal perforation. Binary Logistic regression analysis showed that the total number of leukocytes ( OR=4.085, 95% CI: 1.214-13.745, P=0.023), sharp foreign body ( OR=26.124, 95% CI: 5.194-131.392, P<0.001), and the location of foreign body ( OR=3.980, 95% CI: 1.178-13.465, P=0.026) were the independent risk factors for gastrointestinal perforation. Thirty-three patients underwent gastrointestinal repair surgery, and 36 patients underwent resection and anastomosis of intestine or enterostomy/colostomy. Binary Logistic regression analysis showed that the foreign body located in the colorectum ( OR=71.928, 95% CI: 4.646-1 113.479, P=0.002) and the length of the foreign body ≤2.5 cm ( OR=5.791, 95% CI: 1.606-20.882, P=0.007) were the independent risk factors for resection and anastomosis of intestine or enterostomy/colostomy. Conclusions:Leukocyte count ≥10×10 9/L, sharp foreign body, and location of foreign body are independent risk factors for gastrointestinal perforation. Foreign body located in the colorectum and foreign body length ≤2.5 cm are risk factors for resection and anastomosis of intestine or enterostomy/colostomy.

OBJECTIVE: To explore the clinical and genetic characteristics of five fetuses with Harlequin ichthyosis (HI). METHODS: Five fetuses with HI diagnosed at Guangdong Women and Children Hospital between 2017 and 2024 were selected as study subjects. Clinical and laboratory data were collected and reviewed. Whole exome sequencing (WES) was carried out, and candidate variants were verified by bioinformatic analysis. This study was approved by the Medical Ethics Committee of the hospital (Ethics No.: 202401024). RESULTS: The five fetuses had presented with ectropion, eclabium and contracture and flexion of fingers and toes. WES revealed that all had harbored compound heterozygous or homozygous variants of the ABCA12 gene. Among the eight types of variants, five were unreported previously. CONCLUSION The compound heterozygous or homozygous variants of the ABCA12 gene probably underlay the HI in the five fetuses. Clinicians should be vigilant about the possibility of HI in fetus with ectropion, eclabium, and contracture and flexion of fingers and toes.
Humans ; Ichthyosis, Lamellar/genetics* ; Female ; ATP-Binding Cassette Transporters/genetics* ; Pregnancy ; Genotype ; Phenotype ; Exome Sequencing ; Fetus ; Mutation ; Male ; Adult