OBJECTIVE To establish a full-cycle management model for type 2 diabetes mellitus （T2DM） patients led by clinical pharmacists. METHODS Based on literature research， a basic framework and items of full-cycle management model led by clinical pharmacists were initially formulated. The Delphi method was adopted to conduct questionnaire inquiries among 26 experts to determine the specific implementation items of the model. The analytic hierarchy process （AHP） method was used to determine the weight values of items at all levels， and the reliability and validity of the model items were analyzed. RESULTS The recovery rates of the two rounds of expert consultation questionnaires were 86.67% and 100%， respectively， and the expert authority coefficient was 0.88. Kendall’s concordance coefficients of the tertiary-level items were 0.064 and 0.084， respectively， and the P values from the χ 2 tests were all less than 0.05； the consistent ratios of the judgment matrices for all levels of AHP model were all less than 0.1. The established full-cycle management led by clinical pharmacists comprised three primary-level items （pharmacy service pathway for T2DM patients during hospitalization， pharmacy management pathway for hypoglycemia in T2DM inpatients， and the pharmacy follow-up pathway for T2DM discharged patients， with weights of 0.098， 0.568 and 0.334， respectively）， twelve secondary-level items （e.g. pharmaceutical care during hospitalization for 1 to 2 days， admission assessment and education， with weights ranging from 0.143 to 0.333） and thirty-seven tertiary-level items （e.g. assessment of medication compliance， verification of the medication plan for discharge， with weights ranging from 0.068 to 0.750）. Cronbach’s α coefficients for primary-level items and the overall questionnaire were 0.762， 0.879， 0.928 and 0.951， respectively. The item-level and scale-level content validity indexes were 0.967 and 0.808， respectively. CONCLUSIONS A full-cycle management model for T2DM patients led by clinical pharmacists has been constructed successfully， demonstrating high scientificity and reliability.

Neonatal diabetes mellitus （NDM） is a rare monogenic disorder primarily caused by insufficient insulin secretion resulting from mutations in the KCNJ11 and ABCC8 genes. Sulfonylureas， represented by glibenclamide， have become the standard therapy for this type of NDM by precisely closing the mutated ATP-sensitive potassium channels in pancreatic β cells， thereby restoring insulin secretion. Clinical studies confirm that sulfonylureas enable over 90% of patients to successfully transition from insulin to oral treatment， achieving long-term stable glycemic control and improving neurological outcomes to a certain extent. In terms of safety， severe hypoglycemia induced by sulfonylureas is relatively rare and gastrointestinal reactions are mild； moreover， sulfonylureas show good long-term tolerability， and have no adverse effects on child growth and development. In the future， by further refining the full-chain management pathway of “rapid genetic diagnosis-early intervention-specialized dosage forms-long-term follow-up”， the clinical application of sulfonylureas is expected to provide NDM patients with an optimized treatment regimen and maximize their health benefits.

The invasive brain-computer interface (BCI) is a method that involves implanting microelectrodes into brain tissue to collect neural electrical signals. The signals obtained through this method are often of high precision and relatively stable. However, the chronic fibrotic reaction resulting from long-term implantation can significantly impair the quality of the collected brain electrical signals. Therefore, ensuring the long-term stability of signal acquisition is a major challenge in the development of invasive BCI. This paper systematically reviews the formation mechanisms of fibrosis at the electrode interface, elaborating on the progression from acute inflammatory responses to the development of chronic glial scars and the formation of the extracellular matrix (ECM). It introduces the roles, advantages, and disadvantages of three anti-fibrosis strategies: material and surface optimization, drug and biological factor intervention, and integration of immune regulation and tissue engineering. This paper also evaluates their practical effects and limitations in animal and human clinical applications. Finally, it highlights the importance of establishment of standardized follow-up recording mechanisms in ensuring the long-term reliability and stability of invasive BCIs, providing references and insights for future in-depth interface optimization and clinical translation.

Objective To analyze the epidemiological characteristics and disease burden of liver cancer in Guangdong Province in 2020, and to provide a scientific foundation for the development of regionalized prevention and control strategies for liver cancer. Methods According to the cancer registry data of Guangdong Province, the incidence, mortality and age-standardized rate by Chinese standard population in 2020 were calculated to analyze the epidemiological characteristics of liver cancer. The disability adjusted life years (DALYs), year of life loss (YLL), year of lived with disability (YLD), and cause-eliminated life expectancy were used to assess the disease burden of liver cancer. Results In 2020, the crude incidence rate and the age-standardized incidence rate of liver cancer in Guangdong Province were 27.79/100 000 and 20.84/100 000，respectively, and the crude mortality rate and the age-standardized mortality rate of liver cancer were 25.49/100,000 and 17.64/100 000, respectively. The total DALY and DALY rate of liver cancer in Guangdong Province were 515 311 person-years and 513.83/100 000, respectively. After eliminating the causes of death from liver cancer, the life expectancy in Guangdong Province increased from 84.60 years to 84.99 years. All indicators consistently demonstrated that the burden of liver cancer was higher in males than that in females, and the burden of liver cancer was higher in rural areas than that in urban areas. Conclusion Liver cancer in Guangdong Province exhibits a high incidence, mortality and disease burden level in 2020. There are obvious differences of gender, age and region in cancer burden. It is necessary to strengthen liver cancer screening and diagnosis and treatment in men, the elderly and those in rural areas to reduce the burden of liver cancer gradually in Guangdong Province.

OBJECTIVE To investigate the effects of subanesthetic dose of esketamine on postoperative anxiety and recovery in patients undergoing laparoscopic cholecystectomy. METHODS A total of 200 patients scheduled for laparoscopic cholecystectomy at Suzhou Ninth Hospital Affiliated to Soochow University from January 2023 to December 2024 were randomly assigned to control group （n＝100） and observation group （n＝100）. One minute before the initiation of anesthesia， patients in the control group received intravenous injections of Propofol emulsion injection， Sufentanil citrate injection， and Succinylcholine chloride injection. On this basis， patients in the observation group received an intravenous injection of Esketamine hydrochloride injection. The anxiety status of patients in both groups was compared， along with their general intraoperative conditions （including sufentanil dosage， duration of pneumoperitoneum， operative time， anesthesia time， and extubation time）， postoperative recovery， incidence of adverse reactions， and the need for dezocine rescue analgesia. Heart rate and mean arterial pressure， entropy index （state entropy and response entropy）， inflammatory marker levels [interleukin-6 （IL-6） and C-reactive protein （CRP）]， numerical rating scale （NRS） for pain intensity were compared between the two groups at different time points. RESULTS No significant differences were found between the two groups in pneumoperitoneum duration， operative time， anesthesia time，extubation time， incidence of postoperative dry mouth， entropy index or length of stay in the post-anesthesia care unit （P＞0.05）. Compared with the control group， the observation group showed significantly lower postoperative STAI-S scores， reduced intraoperative sufentanil consumption， decreased incidence of postoperative nausea， vomiting， and shivering， the need for dezocine rescue analgesia， as well as lower plasma IL-6 and CRP levels at 24 h after surgery， and NRS （P＜0.05）. The heart rate and mean arterial pressure of patients in the observation group at the start of surgery， end of surgery， and during extubation were all significantly higher than those in the control group （P＜0.05）. CONCLUSIONS Subanesthetic dose of esketamine can effectively alleviate postoperative anxiety， reduce intraoperative opioid consumption， suppress postoperative inflammatory response， relieve postoperative pain， and promote recovery in patients undergoing laparoscopic cholecystectomy.

Oral squamous cell carcinoma (OSCC) is a common head and neck malignancy. Approximately 50% to 60% of patients with OSCC are diagnosed at a locally advanced stage (clinical staging III-IVa). Even with comprehensive and sequential treatment primarily based on surgery, the 5-year overall survival rate remains below 50%, and patients often suffer from postoperative functional impairments such as difficulties with speaking and swallowing. Programmed death receptor-1 (PD-1) inhibitors are increasingly used in the neoadjuvant treatment of locally advanced OSCC and have shown encouraging efficacy. However, clinical practice still faces key challenges, including the definition of indications, optimization of combination regimens, and standards for efficacy evaluation. Based on the latest research advances worldwide and the clinical experience of the expert group, this expert consensus systematically evaluates the application of PD-1 inhibitors in the neoadjuvant treatment of locally advanced OSCC, covering combination strategies, treatment cycles and surgical timing, efficacy assessment, use of biomarkers, management of special populations and immune related adverse events, principles for immunotherapy rechallenge, and function preservation strategies. After multiple rounds of panel discussion and through anonymous voting using the Delphi method, the following consensus statements have been formulated: 1) Neoadjuvant therapy with PD-1 inhibitors can be used preoperatively in patients with locally advanced OSCC. The preferred regimen is a PD-1 inhibitor combined with platinum based chemotherapy, administered for 2-3 cycles. 2) During the efficacy evaluation of neoadjuvant therapy, radiographic assessment should follow the dual criteria of Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 and immune RECIST (iRECIST). After surgery, systematic pathological evaluation of both the primary lesion and regional lymph nodes is required. For combination chemotherapy regimens, PD-L1 expression and combined positive score need not be used as mandatory inclusion or exclusion criteria. 3) For special populations such as the elderly (≥ 70 years), individuals with stable HIV viral load, and carriers of chronic HBV/HCV, PD-1 inhibitors may be used cautiously under the guidance of a multidisciplinary team (MDT), with close monitoring for adverse events. 4) For patients with a poor response to neoadjuvant therapy, continuation of the original treatment regimen is not recommended; the subsequent treatment plan should be adjusted promptly after MDT assessment. Organ transplant recipients and patients with active autoimmune diseases are not recommended to receive neoadjuvant PD-1 inhibitor therapy due to the high risk of immune related activation. Rechallenge is generally not advised for patients who have experienced high risk immune related adverse events such as immune mediated myocarditis, neurotoxicity, or pneumonitis. 5) For patients with a good pathological response, individualized de escalation surgery and function preservation strategies can be explored. This consensus aims to promote the standardized, safe, and precise application of neoadjuvant PD-1 inhibitor strategies in the management of locally advanced OSCC patients.

Traditional Chinese medicine and its bioactive components have garnered increasing attention as potential therapeutic options for allergic asthma. By targeting the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) signaling pathway, these natural compounds exhibit unique advantages in multilevel immunomodulation and inflammation suppression compared with single-target synthetic drugs. Accumulating pharmacological evidence supports their capacity to restore pathway homeostasis, positioning them as promising candidates for complementary strategies in asthma management. Allergic asthma, a heterogeneous respiratory disorder affecting approximately 150 million individuals worldwide, arises from a complex interplay of genetic predisposition, environmental exposures, and lifestyle factors. Its pathological progression is marked by aberrant activation of the PI3K/AKT signaling cascade, with the mechanistic target of rapamycin serving as a key downstream regulatory node. This evolutionarily conserved pathway orchestrates fundamental cellular processes that contribute to three hallmark pathological features of allergic asthma: chronic airway inflammation, structural remodeling of the bronchial architecture, and airway hyperresponsiveness. This review has 3 primary objectives: (1) to evaluate the role of the PI3K/AKT pathway in allergic asthma pathogenesis, (2) to analyze the molecular mechanisms of representative traditional Chinese medicine preparations and their active ingredients, and (3) to identify novel bioactive inhibitors derived from natural products. Collectively, these investigations provide a conceptual framework for the development of next-generation targeted therapies and for optimizing clinical management strategies for allergic asthma.

Background/Aims: Liver transplantation (LT) following total hepatectomy is a life-saving treatment for hepatocellular carcinoma (HCC). The HCC recurrence after LT hinders the effectiveness of the procedure. The objective of this study is to develop a pre-operative risk stratification model based on a liquid biopsy. Methods: We conducted a comprehensive multi-omics study of 260 HCC patients from three centers, including clinical data, low-coverage whole-genome sequencing of cell-free DNA (cfDNA) from plasma, as well as whole-exome, single-nucleus RNA, and spatial transcriptomics from matched tumor and non-tumor tissues. Results: We identified cfDNA-derived copy number alteration (CNA) signatures associated with post-transplant recurrence. By integrating cfDNA-derived CNA profiles with single-cell transcriptomic data, we traced recurrence-associated cfDNA to a distinct subpopulation of malignant cells within the primary tumor. These cells were embedded in a pro-metastatic microenvironment of specialized endothelial subtypes and cancer-associated fibroblasts. Notably, most recurrence-associated lesions were detectable in cfDNA prior to liver transplantation (LT). Building on these insights, we developed the ZJU Criteria based on CNA fragments and tumor markers, a pre-LT risk prediction tool that integrates conventional clinical factors with cfDNA-derived CNA signatures, and validated it using internal and independent external cohorts. Conclusion Our findings suggest that post-transplant recurrence commonly originates from advanced subclones that emerge late during tumor evolution. The ZJU Criteria provides an accurate, non-invasive strategy that significantly improves pre-LT risk stratification and clinical decision-making for patients with HCC.

This study aimed to establish an analytical method capable of simultaneously quantifying the prototype components of Si-Ni-San and screening their metabolites to elucidate its tissue distribution and metabolic characteristics in an ulcerative colitis (UC) mouse model. To this end, an integrated analysis strategy based on UPLC-QqQ-MS was developed and validated, combining the targeted quantification of 12 prototype components with a pseudo-targeted metabolite screening technique based on ion pair list-triggered data-dependent acquisition. Samples were extracted with 80% methanol (100 mg/mL) and processed with internal standards. Separation was achieved on a Waters Acquity UPLC HSS PFP column using a gradient elution with a mobile phase consisting of acetonitrile and 5 mmol/L ammonium acetate containing 0.1% formic acid. Analysis was performed using an electrospray ionization (ESI) source in multiple reaction monitoring mode. Methodological validation confirmed that all parameters met the requirements for bio-sample analysis. Application of this method revealed that the content of Si-Ni-San prototype components in the colon, liver, and kidneys of UC mice was significantly higher than that in healthy mice. Furthermore, the number of phase II metabolites was markedly greater than that of phase I metabolites in all tested samples. The results demonstrate the reliability of the established method and preliminarily reveal the tissue distribution characteristics of Si-Ni-San under UC conditions and its metabolism pattern dominated by phase II conjugation, which provides a methodological basis and experimental data for further in-depth research into its effective target tissues and pharmacodynamic material basis.

BACKGROUND: Both medication and non-medication therapies are effective approaches to control blood pressure (BP) in hypertension patients. However, the association of joint changes in antihypertensive medication use and healthy lifestyle index (HLI) with BP control among hypertension patients is seldom reported, which needs to provide more evidence by prospective intervention studies. We examined the association of antihypertensive medication use and HLI with BP control among employees with hypertension in China based on a workplace-based multicomponent intervention program. METHODS: Between January 2013 and December 2014, a cluster randomized clinical trial of a workplace-based multicomponent intervention program was conducted in 60 workplaces across 20 urban areas in China. Workplaces were randomly divided into intervention (n = 40) and control (n = 20) groups. Basic information on employees at each workplace was collected by trained professionals, including sociodemographic characteristics, medical history, family history, lifestyle behaviors, medication status and physical measurements. After baseline, the intervention group received a 2-year intervention to achieve BP control, which included: (1) a workplace wellness program for all employees; (2) a guidelines-oriented hypertension management protocol. HLI including nonsmoking, nondrinking, adequate physical activity, weight within reference range and balanced diet, were coded on a 5-point scale (range: 0-5, with higher score indicating a healthier lifestyle). Antihypertensive medication use was defined as taking drug within the last 2 weeks. Changes in HLI, antihypertensive medication use and BP control from baseline to 24 months were measured after the intervention. RESULTS: Overall, 4655 employees were included (age: 46.3 ± 7.6 years, men: 3547 (82.3%)). After 24 months of the intervention, there was a significant improvement in lifestyle [smoking (OR = 0.65, 95% CI: 0.43-0.99; P = 0.045), drinking (OR = 0.52, 95% CI: 0.40-0.68; P < 0.001), regular exercise (OR = 3.10, 95% CI: 2.53-3.78; P < 0.001), excessive intake of fatty food (OR = 0.17, 95% CI: 0.06-0.52; P = 0.002), restrictive use of salt (OR = 0.26, 95% CI: 0.12-0.56; P = 0.001)]. Compare to employees with a deteriorating lifestyle after the intervention, those with an improved lifestyle had a higher BP control. In the intervention group, compared with employees not using antihypertensive medication, those who consistent used (OR = 2.34; 95% CI: 1.16-4.72; P = 0.017) or changed from not using to using antihypertensive medication (OR = 2.24; 95% CI: 1.08-4.62; P = 0.030) had higher BP control. Compared with those having lower HLI, participants with a same (OR = 1.38; 95% CI: 0.99-1.93; P = 0.056) or high (OR = 1.79; 95% CI: 1.27~2.53; P < 0.001) HLI had higher BP control. Those who used antihypertensive medication and had a high HLI had the highest BP control (OR = 1.88; 95% CI: 1.32-2.67, P < 0.001). Subgroup analysis also showed the consistent effect as the above. CONCLUSION These findings suggest that adherence to antihypertensive medication treatment and healthy lifestyle were associated with a significant improvement in BP control among employees with hypertension.