ObjectiveTo investigate the regulatory effects and underlying mechanisms of Liuhuang Zhike prescription （LHZK） on blood glucose in type 2 diabetic db/db mice based on the AMP-activated protein kinase/protein kinase B/glycogen synthase kinase-3β （AMPK/Akt/GSK-3β） signaling pathway. MethodsDb/db mice were used as the model animals， and db/m mice served as the blank control. Forty db/db mice were randomly divided into the model group， metformin group （0.14 g·kg^-1）， and low-， medium-， and high-dose （4.11， 8.21， 16.43 g·kg^-1） LHZK groups， with 8 mice in each group. The db/db mice in the metformin and LHZK groups were administered the corresponding drugs by gavage， while the blank control and model groups were given distilled water by gavage once daily for 8 consecutive weeks. Food intake， water consumption， body weight， and fasting blood glucose （FBG） were measured weekly. An automatic biochemical analyzer was used to determine glycated serum protein （GSP）， serum triglycerides （TG）， total cholesterol （TC）， high-density lipoprotein cholesterol （HDL-C）， and low-density lipoprotein cholesterol （LDL-C） levels. Hematoxylin-eosin （HE） staining was used to observe pathological morphological changes in the liver and pancreatic tissues. Oil red O staining was used to assess lipid accumulation in liver tissue. The anthrone colorimetric method was used to determine hepatic glycogen content. Real-time quantitative PCR （Real-time PCR） was used to detect the mRNA expression levels of insulin receptor substrate-1 （IRS-1）， Akt2， phosphoenolpyruvate carboxykinase （PEPCK）， and glucose-6-phosphatase （G6Pase） in liver tissue. Western blot was used to detect the protein expression of AMPKα， phosphorylated AMPKα （p-AMPKα）， GSK-3β， p-GSK-3β， glycogen synthase （GS）， and phosphorylated GS （p-GS） in liver tissue. ResultsCompared with the blank control group， the model group showed significantly increased food intake， water consumption， body weight， FBG， and GSP levels （P<0.01）. Pancreatic islets exhibited marked parenchymal cell hyperplasia and interstitial inflammatory cell infiltration. Liver tissue showed obvious steatosis， accompanied by a compensatory increase in hepatic glycogen content （P<0.01）. Hepatic G6Pase mRNA expression was increased， while IRS-1 and Akt2 mRNA expression levels were significantly decreased （P<0.01）. The p-AMPKα/AMPKα protein expression ratio showed a decreasing trend， whereas the p-GSK-3β/GSK-3β and p-GS/GS protein expression ratios were significantly increased （P<0.01）. Compared with the model group， food intake and water consumption showed decreasing trends in all treatment groups. Food intake was significantly reduced in the low- and high-dose LHZK groups and in the metformin group （P<0.05， P<0.01）， and water consumption was significantly reduced in the low-dose LHZK group and in the metformin group （P<0.05， P<0.01）. No statistically significant differences in body weight were observed among the LHZK groups， whereas body weight in the metformin group was significantly increased （P<0.05， P<0.01）. FBG showed a decreasing trend in all treatment groups， with significant decreases in the low-dose LHZK group and the metformin group （P<0.05， P<0.01）. GSP levels were significantly reduced in the low-dose LHZK group and in the metformin group （P<0.05， P<0.01）. Hepatic steatosis and pancreatic pathological injury were alleviated to varying degrees in all treatment groups. Hepatic glycogen content further increased in all treatment groups， with significant increases in the medium- and high-dose LHZK groups （P<0.05）. Real-time PCR results showed that all treatment groups downregulated the mRNA expression of G6Pase and PEPCK in the liver tissues of db/db mice， with significant downregulation of PEPCK mRNA in the low-dose LHZK and metformin groups （P<0.01）. Meanwhile， all treatment groups upregulated IRS-1 and Akt2 mRNA expression， with the most pronounced upregulation observed in the medium-dose LHZK group （P<0.01）. The p-AMPKα/AMPKα protein expression ratio was significantly increased in the low- and medium-dose LHZK groups （P<0.01）. The p-GSK-3β/GSK-3β protein expression ratio was significantly increased in all treatment groups （P<0.05， P<0.01）， whereas the p-GS/GS protein expression ratio was significantly decreased in all treatment groups （P<0.01）. ConclusionLHZK effectively reduces FBG and GSP levels in type 2 diabetic mice and improves hepatic steatosis and pancreatic islet pathological injury. Its hypoglycemic mechanism may be associated with regulation of the AMPK/Akt/GSK-3β signaling pathway and promotion of hepatic glycogen synthesis.

OBJECTIVE To form an expert consensus on the clinical application of parenteral direct thrombin inhibitors （DTIs） in patients during the perioperative period. METHODS Led by Sichuan Academy of Medical Sciences & Sichuan Provincial People’s Hospital （the Affiliated Hospital of UESTC）， a multidisciplinary working group was established. Through literature review and the Delphi method， clinical questions related to the rational perioperative use of parenteral DTIs were identified. A structured design was adopted using the “Population-Intervention-Comparison-Outcome” framework； systematic searches were conducted in CNKI， Medline， Embase and other databases. Relevant evidence from randomized controlled trials and cohort studies was included and synthesized. Evidence quality was assessed using the Grades of Recommendations Assessment，Development and Evaluation （GRADE） approach， and recommendations were formulated through multiple rounds of Delphi surveys and expert consensus meetings. RESULTS &CONCLUSIONS Seven recommendations （each with an expert consensus rate exceeding 90%） on the use of parenteral DTIs in perioperative patients were developed. These recommendations specify drug selection， dosing ranges， key monitoring points， and safety management strategies for parenteral DTIs in various scenarios， including the perioperative period of ventricular assist device implantation， the perioperative period of cardiac surgery， perioperative patients with lower-extremity atherosclerotic disease， the perioperative period of percutaneous coronary intervention in patients with acute coronary syndrome， the perioperative period of carotid artery stenting in patients with carotid stenosis， the perioperative period of patients with right heart thrombosis， and patients who develop related thrombosis and dysfunction after a central venous catheter insertion. In addition， warning and management pathways for perioperative bleeding and thrombotic events were proposed. This expert consensus， which is formulated based on the best available evidence， provides evidence-based guidance for standardized and individualized use of parenteral DTIs in perioperative period.

Diabetes is a very complex endocrine disease whose common feature is the increase in blood glucose concentration. Persistent hyperglycemia can lead to blindness, kidney and heart disease, neurodegeneration, and many other serious complications that have a significant impact on human health and quality of life. The number of people with diabetes is increasing yearly. The global diabetes prevalence in 20-79 year olds in 2021 was estimated to be 10.5% (536.6 million), and it will rise to 12.2% (783.2 million) in 2045. The main modes of intervention for diabetes include medication, dietary management, and exercise conditioning. Medication is the mainstay of treatment. Marketed diabetes drugs such as metformin and insulin, as well as GLP-1 receptor agonists, are effective in controlling blood sugar levels to some extent, but the preventive and therapeutic effects are still unsatisfactory. Peptide drugs have many advantages such as low toxicity, high target specificity, and good biocompatibility, which opens up new avenues for the treatment of diabetes and other diseases. Currently, insulin and its analogs are by far the main life-saving drugs in clinical diabetes treatment, enabling effective control of blood glucose levels, but the risk of hypoglycemia is relatively high and treatment is limited by the route of delivery. New and oral anti-diabetic drugs have always been a market demand and research hotspot. Inhibitor cystine knot (ICK) peptides are a class of multifunctional cyclic peptides. In structure, they contain three conserved disulfide bonds (C3-C20, C7-C22, and C15-C32) form a compact “knot” structure, which can resist degradation of digestive protease. Recent studies have shown that ICK peptides derived from legume, such as PA1b, Aglycin, Vglycin, Iglycin, Dglycin, and aM₁, exhibit excellent regulatory activities on glucose and lipid metabolism at the cellular and animal levels. Mechanistically, ICK peptides promote glucose utilization by muscle and liver through activation of IR/AKT signaling pathway, which also improves insulin resistance. They can repair the damaged pancrease through activation of PI3K/AKT/Erk signaling pathway, thus lowering blood glucose. The biostability and hypoglycemic efficacy of the ICK peptides meet the requirements for commercialization of oral drugs, and in theory, they can be developed into natural oral anti-diabetes peptide drugs. In this review, the structural properties, activity and mechanism of ICK pattern peptides in regulating glucose and lipid metabolism were summaried, which provided a reference for the development of new oral peptides for diabetes.

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.

Roxadustat is the world's first small molecule hypoxia-inducible factor prolyl hydroxylase inhibitor. Its adverse effect of causing hypothyroidism with low thyroid-stimulating hormone (TSH) is relatively rare and manifests subtly in elderly patients with multiple coexisting diseases. This article reports a case of an elderly patient with renal anemia who developed reversible low-TSH hypothyroidism after taking roxadustat for 12 days, with a significant decrease in thyroid hormone levels. After discontinuing roxadustat for 15 days, the thyroid hormone levels gradually returned to normal. Due to the worsening of renal anemia, the patient took roxadustat again, and 9 days later, the thyroid function-related indicators decreased upon re-examination, leading to the initiation of levothyroxine replacement therapy. In conjunction with relevant literature, this article analyzes the adverse reactions that occur during the oral administration of roxadustat in elderly patients with chronic kidney disease, aiming to provide reference for drug treatment of such patients.

Phacoemulsification with intraocular lens implantation(Phaco+lOL)has become the main treatment for cataracts due to small incision and fast recovery. Phacoemulsification can damage the conjunctiva, cornea and other ocular surface tissues, causing local inflammation, which in turn leads to eye dryness and discomfort after surgery. According to studies, patients who suffer from phacoemulsification most experience dry eye syndrome within 24 h, which gradually worsens and reaches its peak in the following 1 wk, seriously affecting their quality of life. The review aims to comprehensively investigate the effects of preoperative patient physical conditions and local ocular status, intraoperative maneuvers and postoperative treatments on postoperative dry eye, with the expectation of formulating scientific and effective preventive measures for potential dry eye patients after phacoemulsification, and providing a theoretical basis for postoperative dry eye treatment.

ObjectiveNeuroinflammation plays a crucial role in both the onset and progression of ischemic stroke, exerting a significant impact on the recovery of the central nervous system. Excessive neuroinflammation can lead to secondary neuronal damage, further exacerbating brain injury and impairing functional recovery. As a result, effectively modulating and reducing neuroinflammation in the brain has become a key therapeutic strategy for improving outcomes in ischemic stroke patients. Among various approaches, targeting immune regulation to control inflammation has gained increasing attention. This study aims to investigate the role of in vitro induced regulatory T cells (Treg cells) in suppressing neuroinflammation after ischemic stroke, as well as their potential therapeutic effects. By exploring the mechanisms through which Tregs exert their immunomodulatory functions, this research is expected to provide new insights into stroke treatment strategies. MethodsNaive CD4⁺ T cells were isolated from mouse spleens using a negative selection method to ensure high purity, and then they were induced in vitro to differentiate into Treg cells by adding specific cytokines. The anti-inflammatory effects and therapeutic potential of Treg cells transplantation in a mouse model of ischemic stroke was evaluated. In the middle cerebral artery occlusion (MCAO) model, after Treg cells transplantation, their ability to successfully migrate to the infarcted brain region and their impact on neuroinflammation levels were examined. To further investigate the role of Treg cells in stroke recovery, the changes in cytokine expression and their effects on immune cell interactions was analyzed. Additionally, infarct size and behavioral scores were measured to assess the neuroprotective effects of Treg cells. By integrating multiple indicators, the comprehensive evaluation of potential benefits of Treg cells in the treatment of ischemic stroke was performed. ResultsTreg cells significantly regulated the expression levels of both pro-inflammatory and anti-inflammatory cytokines in vitro and in vivo, effectively balancing the immune response and suppressing excessive inflammation. Additionally, Treg cells inhibited the activation and activity of inflammatory cells, thereby reducing neuroinflammation. In the MCAO mouse model, Treg cells were observed to accumulate in the infarcted brain region, where they significantly reduced the infarct size, demonstrating their neuroprotective effects. Furthermore, Treg cell therapy notably improved behavioral scores, suggesting its role in promoting functional recovery, and increased the survival rate of ischemic stroke mice, highlighting its potential as a promising therapeutic strategy for stroke treatment. ConclusionIn vitro induced Treg cells can effectively suppress neuroinflammation caused by ischemic stroke, demonstrating promising clinical application potential. By regulating the balance between pro-inflammatory and anti-inflammatory cytokines, Treg cells can inhibit immune responses in the nervous system, thereby reducing neuronal damage. Additionally, they can modulate the immune microenvironment, suppress the activation of inflammatory cells, and promote tissue repair. The therapeutic effects of Treg cells also include enhancing post-stroke recovery, improving behavioral outcomes, and increasing the survival rate of ischemic stroke mice. With their ability to suppress neuroinflammation, Treg cell therapy provides a novel and effective strategy for the treatment of ischemic stroke, offering broad application prospects in clinical immunotherapy and regenerative medicine.

Objective: To retrospectively compare the safety and efficacy of ultrasound-guided radiofrequency ablation (RFA) with parotidectomy for superficial pleomorphic adenoma (PA). Materials and Methods: From March 2022 to October 2023, 88 patients diagnosed with superficial parotid PA underwent either RFA (n = 12; mean age, 47.1 years) or parotidectomy (n = 76; mean age, 47.8 years). Patients in the RFA group were matched to those in the surgery group in a 1:1 ratio using propensity scores based on age, sex, tumor volume, diameter, location, and comorbidities. Ultrasound characteristics, cosmetic scores (0–4), numerical rating scale scores (0–10), and complications were assessed before the procedures and at 1-, 3-, and 6-month follow-ups. Outcomes were compared between baseline and follow-up in the RFA group and between the RFA and surgery groups. Results: In the RFA group, significant reductions in tumor volume were observed between baseline (median, 2.02 cm 3 ) and the 1-month follow-up (median, 1.21 cm 3 ; P = 0.015), between the 1-month and 3-month follow-ups (median, 0.53 cm 3 ; P= 0.002), and between the 3- and 6-month follow-ups (median, 0.23 cm 3 ; P = 0.003). The volume reduction ratios at 1, 3, and 6 months were 39.7%, 79.9%, and 88.0%, respectively. The cosmetic score was significantly lower at 3- and 6-month followup compared to baseline (median 1 and 1 vs. 4, P = 0.04). The numerical rating scale scores did not differ significantly from baseline throughout follow-up. In the propensity score-matched analysis (12 patients per group), RFA was associated with a shorter median procedure time (61.5 vs. 253.3 minutes; P < 0.001), shorter hospital stay (0 vs. 4 days; P < 0.001), and lower cost (1859.9 vs. 3512.4 USD; P < 0.001) than parotidectomy, with no significant difference in overall complication rates (33.3% [4/12] vs. 41.7% [5/12]; P = 1.000). Conclusion RFA may be a safe and effective alternative to surgery for superficial parotid PA, offering a shorter median procedure time, shorter hospital stay, and lower costs.

Objective: The clinical presentation of depressive disorders might be influenced by age, and its diagnosis and treatment can be affected by ageism-related bias. A network analysis can reveal symptom patterns unrecognized by the reductionistic approach. Therefore, this study explores the network structure of depression and anxiety symptoms in older Asian patients with depressive disorders and examines age-related differences in the context of ageism. Methods: We used data from the Research on Asian Psychotropic Prescription Patterns for Antidepressants, Phase 3 study and included 2,785 psychiatric patients from 11 Asian countries. Depression and anxiety symptoms were assessed using the Patient Health Questionnaire-9 and Generalized Anxiety Disorder-7. Network analyses were conducted to identify symptom interconnections and centrality among older (>65 years), middle-aged (35–64 years), and young (18–34 years) adult groups. The network structures were also compared using a network comparison test. Results: Depressed mood was the most central symptom across all age groups. Network comparisons revealed no significant structural differences among the three age groups, despite several variations in terms of global strength. The network structure of the older group was characterized by strong interconnections between somatic symptoms (insomnia-energy) and core depressive symptoms (little interest or pleasure-feelings of hopelessness). Conclusion This study reveals that the network structures of depression and anxiety symptoms have relatively consistent interconnections across age groups, despite subtle age-based differences. Specifically, older adults tend to present anxiety and depression symptoms as physical complaints. These findings challenge ageist stereotypes and advocate for inclusive, age-neutral approaches to treatment.

Objective: To retrospectively compare the safety and efficacy of ultrasound-guided radiofrequency ablation (RFA) with parotidectomy for superficial pleomorphic adenoma (PA). Materials and Methods: From March 2022 to October 2023, 88 patients diagnosed with superficial parotid PA underwent either RFA (n = 12; mean age, 47.1 years) or parotidectomy (n = 76; mean age, 47.8 years). Patients in the RFA group were matched to those in the surgery group in a 1:1 ratio using propensity scores based on age, sex, tumor volume, diameter, location, and comorbidities. Ultrasound characteristics, cosmetic scores (0–4), numerical rating scale scores (0–10), and complications were assessed before the procedures and at 1-, 3-, and 6-month follow-ups. Outcomes were compared between baseline and follow-up in the RFA group and between the RFA and surgery groups. Results: In the RFA group, significant reductions in tumor volume were observed between baseline (median, 2.02 cm 3 ) and the 1-month follow-up (median, 1.21 cm 3 ; P = 0.015), between the 1-month and 3-month follow-ups (median, 0.53 cm 3 ; P= 0.002), and between the 3- and 6-month follow-ups (median, 0.23 cm 3 ; P = 0.003). The volume reduction ratios at 1, 3, and 6 months were 39.7%, 79.9%, and 88.0%, respectively. The cosmetic score was significantly lower at 3- and 6-month followup compared to baseline (median 1 and 1 vs. 4, P = 0.04). The numerical rating scale scores did not differ significantly from baseline throughout follow-up. In the propensity score-matched analysis (12 patients per group), RFA was associated with a shorter median procedure time (61.5 vs. 253.3 minutes; P < 0.001), shorter hospital stay (0 vs. 4 days; P < 0.001), and lower cost (1859.9 vs. 3512.4 USD; P < 0.001) than parotidectomy, with no significant difference in overall complication rates (33.3% [4/12] vs. 41.7% [5/12]; P = 1.000). Conclusion RFA may be a safe and effective alternative to surgery for superficial parotid PA, offering a shorter median procedure time, shorter hospital stay, and lower costs.