OBJECTIVE To investigate a dynamic monitoring of drug consumption （DMDC） model based on the seasonal Mann-Kendall trend test， aiming to provide scientific evidence for the efficient and macroscopic monitoring of drug use. METHODS A monitoring list of key outpatient drugs was established based on the top 20% of drugs ranked by sales volume in the outpatient pharmacy in October 2024. A DMDC model based on the Mann-Kendall trend test was constructed using the monthly usage data of key outpatient drugs from November 2021 to October 2024， aiming to eliminate the impact of seasonal fluctuations and analyze the temporal trends in drug consumption. Taking mucolytic expectorants， triazole derivatives for dermatophytosis， and single-agent hydroxymethylglutaryl coenzyme A （HMG-CoA） reductase inhibitors as examples， the monitoring effectiveness of the DMDC model was demonstrated， and its performance was compared with that achieved by the traditional sequential growth rate ranking method. RESULTS A total of 215 drug varieties were included in the monitoring list， and DMDC models were successfully established for all of them. Among these， 119 showed a significant increasing trend （P＜0.05， S′＞0）. The model successfully monitored the monthly consumption of mucolytic expectorants， triazole derivatives for dermatophytosis， and single- agent HMG-CoA reductase inhibitors. The precision and recall rates of the DMDC model for identifying abnormal drug use were 60.7% and 85.0%， respectively， both significantly higher than those of the sequential growth rate ranking method （8.3% and 15.0%， respectively） （χ2＝20.114， P＜0.001； χ2＝19.600， P＜0.001）. CONCLUSIONS DMDC model based on the seasonal Mann-Kendall trend test can effectively identify long-term trends in drug consumption， eliminate seasonal interference， enhance monitoring accuracy and management efficiency， and is suitable for the dynamic monitoring of drug consumption.

OBJECTIVE To provide scientific evidence and practical references for refined antimicrobial stewardship in multi- branch medical institutions. METHODS Data of antibiotic use density （AUD） of inpatients as well as physician-level case mix index （CMI） were collected from the Liji Road main campus and Panlongcheng branch campus of our hospital from August 2023 to March 2026. The two-factor decomposition method was adopted to decompose total AUD variation into a level effect and structural effect. Grey relational analysis （GRA） was performed to quantify the correlation degree between ward CMI， physician CMI and physician AUD， so as to identify wards and physicians requiring targeted key intervention in different campuses. A refined antimicrobial management framework for multi-branch hospitals was constructed and implemented based on the above analytical results. An interrupted time series （ITS） model incorporating seasonal dummy variables was applied. The research period was divided into pre-intervention stage （August 2023 to March 2024） and post-intervention stage （April 2024 to March 2026）. The temporal changing trends of AUD in two campuses were compared to evaluate management efficacy. RESULTS Driving factors for AUD variation presented significant heterogeneity between the two campuses. AUD variation in the main campus was dominated by level effect， while AUD variation in the branch campus was jointly affected by structural effect and level effect. The grey relational degrees of ward CMI and physician CMI with physician AUD were 0.901 and 0.882， respectively. After refined management implementation， AUD decreased by 7.48 DDDs/（100 bed·days） and 20.54 DDDs/（100 bed·days） in the main campus and branch campus， respectively； the rising trends of AUD in both campuses reversed to declining trends after intervention. CONCLUSIONS Driving factors of AUD variation under the multi-branch hospital model show obvious inter-campus heterogeneity. CMI is highly correlated with AUD. The refined management system developed via AUD attribution decomposition and CMI correlation analysis matches the differentiated clinical characteristics of multi- branch hospitals and effectively improves the precision of antimicrobial stewardship.

Hearing loss is the most prevalent disabling disease. Cochlear implantation（CI） serves as the primary intervention for severe to profound hearing loss. This consensus systematically explores the value of genetic diagnosis in the pre-operative assessment and efficacy prognosis for CI. Drawing upon domestic and international research and clinical experience, it proposes an evidence-based medicine three-tiered prognostic classification system（Favorable, Marginal, Poor）. The consensus focuses on common hereditary non-syndromic hearing loss（such as that caused by mutations in genes like GJB2, SLC26A4, OTOF, LOXHD1） and syndromic hereditary hearing loss（such as Jervell & Lange-Nielsen syndrome and Waardenburg syndrome）, which are closely associated with congenital hearing loss, analyzing the impact of their pathological mechanisms on CI outcomes. The consensus provides recommendations based on multiple round of expert discussion and voting. It emphasizes that genetic diagnosis can optimize patient selection, predict prognosis, guide post-operative rehabilitation, offer stratified management strategies for patients with different genotypes, and advance the application of precision medicine in the field of CI.
Humans ; Cochlear Implantation ; Prognosis ; Hearing Loss/surgery* ; Consensus ; Connexin 26 ; Mutation ; Sulfate Transporters ; Connexins/genetics*

Cancer immunotherapy has emerged as a promising strategy. However, low response rates and immune-related side effects have plagued immunotherapy. Metallic nanoparticles, utilizing metals as their framework, are gaining prominence in cancer immunotherapy. Metal ions have shown the ability to modulate immune status by activating the cGAS-STING pathway and inducing immunogenic cell death (ICD), thereby enabling multidimensional activation of immunotherapy. Metallic nanoparticles offer significant advantages in cancer immunotherapy, leading to their increasing use in enhancing therapeutic outcomes. In view of the ever-increasing research on metallic nanoparticles, this review presents the construction, characterization, and enhanced cancer immunotherapeutic effects of different types of metal nanosystems from the perspective of the immunoregulatory mechanisms of metal ions. We delve into the current limitations and future directions of metallic nanoparticles in this rapidly evolving field. To the best of our knowledge, this review offers the most up-to-date and systematic analysis of metallic nanoparticles in immunotherapeutic applications. It is anticipated that this review of metallic nanoparticles will inspire a more refined and intelligent design of metallic nanoparticles for future research, paving the way for advancing their clinical applications.

Objective To investigate effect of cassava RS3 resistant starch(Ce-RS3)on serum homocysteine(Hcy)level in patients with atherosclerotic cerebral infarction(ACI)during the recovery period.Methods A total of 55 patients with ACI at the First Affiliated Hospital of Guizhou University of Traditional Chinese Medicine from October 2023 to October 2024 were selected as subjects.They were devieded into observation group(n=28)and control group(n=27)using a random number table.The control group received atorvastatin calcium,phospholipids,and aspirin,while the observation group received atorvastatin calcium,phospholipids,aspirin,and Ce-RS3.After 12 weeks of treatment,homocysteine(Hcy)levels,carotid plaque diameter,National Institutes of Health stroke scale(NIHSS)scores,Barthel index(BI)scores,and traditional Chinese medicine(TCM)syndrome scores were compared between two groups.Results After treatment,the serum Hcy levels decreased and carotid plaque size reduced in both groups,with the NIHSS scores and TCM syndrome scores also decreased,and observation group was lower than control group(P＜0.05).After treatment,the BI score increased,with observation group higher than control group(P＜0.05).Conclusion The use of Ce-RS3 in the recovery phase of patients with ACI can effectively improve neurological function and enhance treatment efficacy.

Objective:To assess the value of whole exome sequencing (WES) for the diagnosis of early-onset genetic diseases among infants aged 0 to 6 month in Ningbo region.Methods:268 infants presented at the Women and Children′s Hospital Affiliated to Ningbo University from January 2022 to June 2024 undergoing WES-based genetic testing were enrolled. Peripheral blood samples were collected from the infants and their parents and subjected to WES. Pathogenic variants were identified by clinical manifestations. This study has been approved by the Medical Ethics Committee of the Hospital (Ethics No. EC2023-017).Results:Among the 268 infants, 124 (46.3%) had phenotype-explaining genetic variants. For 42 family-based WES tests, 20 (47.62%) were abnormal, whilst in 226 single-person WES tests, 104 (46.02%) had abnormalities, with 76 (33.63%) verified by parental testing. In 96 fully family-verified cases, 31 were de novo, 40 were parent-inherited, 25 were single-parent-inherited. These included 35 inborn metabolic errors, 28 rare syndromes, 9 neurodevelopmental disorders, 4 musculoskeletal diseases, 5 congenital deafness, 2 mitochondrial diseases, 4 endocrine diseases, and 9 others. Among these, there were 7 pathogenic copy number variations (all deletions), 3 chromosomal abnormalities, and 85 single-nucleotide variations. One case of Beckwith-Wiedemann syndrome was detected by methylation MLPA. Among the single-nucleotide variants, 114 pathogenic/likely pathogenic variants were identified in 61 genes, with common ones including missense variants (64.04%), frameshifting variants (20.18%) and splicing variants (4.39%). Conclusion:WES can offer effective diagnosis for hereditary diseases with specific/non-specific manifestations. For early-age infants, higher detection rates may be attained for inborn metabolic errors, rare syndromes, neurodevelopmental disorders, congenital deafness, and musculoskeletal diseases. Compared with single-person WES, family-based WES can attain a higher diagnostic efficiency.

Objective:To explore the genetic characteristics and pathogenesis for a child with mosaicism trisomy 21 and Congenital leukemia (CL).Methods:A child who was admitted to Ningbo Women and Children′s Hospital in March 2023 was selected as the study subject. A retrospective analysis was carried out on the clinical data, laboratory test results, immunophenotyping, and genetic characteristics of the child. This study was approved by the Medical Ethics Committee of the Hospital (Ethics No.: EC2024-063).Results:Whole genome sequencing (WGS) revealed that the child has mosaicism trisomy of chromosome 21, with a ratio of approximately 74%. In addition, pathogenic copy number variations involving multiple OMIM genes that could explain his clinical phenotype were detected and rated as pathogenic based on the guidelines from the American College of Medical Genetics and Genomics (ACMG). No pathogenic variant was detected with the GATA1 gene. Blood immune typing of the child conformed to the immunophenotype of acute myeloid leukemia. Conclusion:For children with trisomy 21, even in the absence of GATA1 gene variants, the occurrence of CL should be monitored, and early diagnosis and treatment are of great significance for improving the prognosis.

Objective:To explore the clinical characteristics and genetic etiology of a child with Oral-facial-digital syndrome type Ⅰ(OFDSⅠ).Method:A child with OFDSⅠ who received treatment at the Women and Children′s Hospital Affiliated to Ningbo University in March 2023 was selected as the study subject. A retrospective research method was used to collect the clinical data of the child. Peripheral venous blood samples were collected from the child, her parents and sister. Genomic DNA was extracted, and whole exome sequencing (WES) was performed. Candidate variants were validated using Sanger sequencing for familial verification. According to the Standards and Guidelines for the Interpretation of Sequence Variants developed by the American College of Medical Genetics and Genomics (ACMG) (hereinafter referred to as the " ACMG Guidelines" ), the pathogenicity of the candidate variant was rated. This study was approved by the Medical Ethics Committee of Ningbo University Affiliated Women and Children′s Hospital (Ethic No.: EC 2024-063).Results:The child was a prematurely born female with deformities of the oral cavity, fingers, and toes. She was admitted to the Neonatal Department of the Hospital where she was born due to shortness of breath 15 minutes after birth. The WES results indicated that the child has harbored a heterozygous c. 710dup(p.Y238Vfs*2) frameshifting variant of the OFD1 gene. Sanger sequencing confirmed that neither of the child′s parents nor her sister had carried the same variant. According to the ACMG guidelines, the variant was rated as pathogenic (PVS1+ PS4_Moderate+ PM2-Supporting+ PM6_Supporting+ PP4). Conclusion:Children with OFDSⅠ have clinical features such as oral, finger, and toe deformities. The c. 710dup(p.Y238Vfs*2) variant of the OFD1 gene probably underlay the OFDSⅠ in this child. Above result has enriched the mutational spectrum of the OFD1 gene.

This study aimed to comprehensively examine the association of gallstones, cholecystectomy, and cancer risk. Multivariable logistic regressions were performed to estimate the observational associations of gallstones and cholecystectomy with cancer risk, using data from a nationwide cohort involving 239 799 participants. General and gender-specific two-sample Mendelian randomization (MR) analysis was further conducted to assess the causalities of the observed associations. Observationally, a history of gallstones without cholecystectomy was associated with a high risk of stomach cancer (adjusted odds ratio (aOR)=2.54, 95% confidence interval (CI) 1.50-4.28), liver and bile duct cancer (aOR=2.46, 95% CI 1.17-5.16), kidney cancer (aOR=2.04, 95% CI 1.05-3.94), and bladder cancer (aOR=2.23, 95% CI 1.01-5.13) in the general population, as well as cervical cancer (aOR=1.69, 95% CI 1.12-2.56) in women. Moreover, cholecystectomy was associated with high odds of stomach cancer (aOR=2.41, 95% CI 1.29-4.49), colorectal cancer (aOR=1.83, 95% CI 1.18-2.85), and cancer of liver and bile duct (aOR=2.58, 95% CI 1.11-6.02). MR analysis only supported the causal effect of gallstones on stomach, liver and bile duct, kidney, and bladder cancer. This study added evidence to the causal effect of gallstones on stomach, liver and bile duct, kidney, and bladder cancer, highlighting the importance of cancer screening in individuals with gallstones.
Humans ; Mendelian Randomization Analysis ; Gallstones/complications* ; Female ; Male ; Cholecystectomy/statistics & numerical data* ; Middle Aged ; Risk Factors ; Aged ; Adult ; Neoplasms/etiology* ; Stomach Neoplasms/epidemiology*