Objective This study aimed to explore the spatial heterogeneity and risk factors for dental caries in 12-year-old children in Shanxi province,China. Methods The data encompassed 3,721 participants from the two most recent oral health surveys conducted across 16 districts in Shanxi Province in 2015 and 2018.Eighteen specific variables were analyzed to examine the interplay between socioeconomic factors,medical resources and environmental conditions.The Geo-detector model was employed to assess the impacts and interactions of these ecological factors. Results Socioeconomic factors(Q=0.30,P<0.05)exhibited a more substantial impact compared to environmental(Q=0.19,P<0.05)and medical resource factors(Q=0.25,P<0.05).Notably,the urban population percentage(UPP)demonstrated the most significant explanatory power for the spatial heterogeneity in caries prevalence,as denoted by its highest q-value(q=0.51,P<0.05).Additionally,the spatial distribution's heterogeneity of caries was significantly affected by SO2 concentration(q=0.39,P<0.05)and water fluoride levels(q=0.27,P<0.05)among environmental factors. Conclusion The prevalence of caries exhibited spatial heterogeneity,escalating from North to South in Shanxi Province,China,influenced by socioeconomic factors,medical resources,and environmental conditions to varying extents.

Objective:To investigate the clinical characteristics of choledocholithiasis com-bined with periampullary diverticulum and influencing factor for difficult cannulation of endoscopic retrograde cholangiopancreatography (ERCP).Methods:The retrospective case-control study was conducted. The clinical data of 1 920 patients who underwent ERCP for choledocholithiasis in 15 medical centers, including the First Hospital of Lanzhou University, et al, from July 2015 to December 2017 were collected. There were 915 males and 1 005 females, aged (63±16)years. Of 1 920 patients, there were 228 cases with periampullary diverticulum and 1 692 cases without periampullary diverticulum. Observation indicators: (1) clinical characteristics of patients with choledocholithiasis; (2) intraoperative and postoperative situations of patients undergoing ERCP for choledocholithiasis; (3) influencing factor analysis for difficult cannulation in patients undergoing ERCP for choledocholithiasis. Measurement data with normal distribution were represented as Mean±SD, and comparison between groups was conducted using the independent sample t test. Measurement data with skewed distribution were represented as M(range) or M( Q1, Q3), and com-parison between groups was conducted using the Wilcoxon rank sum test. Count data were described as absolute numbers or percentages, and comparison between groups was conducted using the chi-square test or Fisher exact probability. The Logistic regression model was used for univariate and multivariate analyses. Results:(1) Clinical characteristics of patients with choledocholithiasis. Age, body mass index, cases with complications as chronic obstructive pulmonary disease, diameter of common bile duct, cases with diameter of common bile duct as <8 mm, 8?12 mm, >12 mm, diameter of stone, cases with number of stones as single and multiple were (69±12)years, (23.3±3.0)kg/m 2, 16, (14±4)mm, 11, 95, 122, (12±4)mm, 89, 139 in patients with choledocholithiasis combined with periampullary diverticulum, versus (62±16)years, (23.8±2.8)kg/m 2, 67, (12±4)mm, 159, 892, 641, (10±4)mm, 817, 875 in patients with choledocholithiasis not combined with periampullary diver-ticulum, showing significant differences in the above indicators between the two groups ( t=?7.55, 2.45, χ2=4.54, t=?4.92, Z=4.66, t=?7.31, χ2=6.90, P<0.05). (2) Intraoperative and postoperative situations of patients undergoing ERCP for choledocholithiasis. The balloon expansion diameter, cases with intraoperative bleeding, cases with hemorrhage management of submucosal injection, hemostatic clip, spray hemostasis, electrocoagulation hemostasis and other treatment, cases with endoscopic plastic stent placement, cases with endoscopic nasal bile duct drainage, cases with mechanical lithotripsy, cases with stone complete clearing, cases with difficult cannulation, cases with delayed intubation, cases undergoing >5 times of cannulation attempts, cannulation time, X-ray exposure time, operation time were 10.0(range, 8.5?12.0)mm, 56, 6, 5, 43, 1, 1, 52, 177, 67, 201, 74, 38, 74, (7.4±3.1)minutes, (6±3)minutes, (46±19)minutes in patients with choledocholithiasis combined with periampullary diverticulum, versus 9.0(range, 8.0?11.0)mm, 243, 35, 14, 109, 73, 12, 230, 1 457, 167, 1 565, 395, 171, 395, (6.6±2.9)minutes, (6±5)minutes, (41±17)minutes in patients with choledocholithiasis not combined with periampullary diverticulum, showing significant differences in the above indicators between the two groups ( Z=6.31, χ2=15.90, 26.02, 13.61, 11.40, 71.51, 5.12, 9.04, 8.92, 9.04, t=?3.89, 2.67, ?3.61, P<0.05). (3) Influencing factor analysis for difficult cannulation in patients undergoing ERCP for choledocholithiasis. Results of multivariate analysis showed total bilirubin >30 umol/L, number of stones >1, combined with periampullary diverticulum were indepen-dent risk factors for difficult cannulation in patients with periampullary diverticulum who underwent ERCP for choledocholithiasis ( odds ratio=1.31, 1.48, 1.44, 95% confidence interval as 1.06?1.61, 1.20?1.84, 1.06?1.95, P<0.05). Results of further analysis showed that, of 1 920 patients undergoing ERCP for choledocholithiasis, the incidence of postoperative pancreatitis was 17.271%(81/469) and 8.132%(118/1 451) in the 469 cases with difficult cannulation and 1 451 cases without difficult cannula-tion, respectively, showing a significant difference between them ( χ2=31.86, P<0.05). In the 1 692 patients with choledocholithiasis not combined with periampullary diverticulum, the incidence of postopera-tive pancreatitis was 17.722%(70/395) and 8.250%(107/1 297) in 395 cases with difficult cannula-tion and 1 297 cases without difficult cannulation, respectively, showing a significant difference between them ( χ2=29.00, P<0.05). In the 228 patients with choledocholithiasis combined with peri-ampullary diverticulum, the incidence of postoperative pancreatitis was 14.865%(11/74) and 7.143%(11/154) in 74 cases with difficult cannulation and 154 cases without difficult cannulation, respectively, showing no significant difference between them ( χ2=3.42, P>0.05). Conclusions:Compared with patients with choledocholithiasis not combined with periampullary divertioulum, periampullary divertioulum often occurs in choledocholithiasis patients of elderly and low body mass index. The proportion of chronic obstructive pulmonary disease is high in choledocholithiasis patients with periampullary diverticulum, and the diameter of stone is large, the number of stone is more in these patients. Combined with periampullary diverticulum will increase the difficult of cannulation and the ratio of patient with mechanical lithotripsy, and reduce the ratio of patient with stone complete clearing without increasing postoperative complications of choledocholithiasis patients undergoing ERCP. Total bilirubin >30 μmol/L, number of stones >1, combined with periampullary diverticulum are independent risk factors for difficult cannulation in patients of periampullary diverticulum who underwent ERCP for choledocholithiasis.

Chronic refractory wound (CRW) is one of the most challengeable issues in clinic due to complex pathogenesis, long course of disease and poor prognosis. Experts need to conduct systematic summary for the diagnosis and treatment of CRW due to complex pathogenesis and poor prognosis, and standard guidelines for the diagnosis and treatment of CRW should be created. The Guideline forthe diagnosis and treatment of chronic refractory wounds in orthopedic trauma patients ( version 2023) was created by the expert group organized by the Chinese Association of Orthopedic Surgeons, Chinese Orthopedic Association, Chinese Society of Traumatology, and Trauma Orthopedics and Multiple Traumatology Group of Emergency Resuscitation Committee of Chinese Medical Doctor Association after the clinical problems were chosen based on demand-driven principles and principles of evidence-based medicine. The guideline systematically elaborated CRW from aspects of the epidemiology, diagnosis, treatment, postoperative management, complication prevention and comorbidity management, and rehabilitation and health education, and 9 recommendations were finally proposed to provide a reliable clinical reference for the diagnosis and treatment of CRW.

Objective:To evaluate the specialty of the clinical features, treatment procedure, clinical outcome, and prognosis in the patients with "sandwich" atlantoaxial dislocation (AAD).Methods:From 2008 to 2018, 160 cases with "sandwich" AAD were retrospectively selected from the case series of AAD in Peking University Third Hospital. The case series had 80 males and 80 females. The mean age at the initial visit was 35.5±14.6 years (range, 5-77). The clinical courses, treatment methodology and prognosis were reviewed. And the surgical approach, posterior fixation segment and the recovery of neurological function were mainly summarized. The atlantodental interval (ADI), the distance by which the odontoid exceeded the Chamberlain line and the cervical-medullary angle were analyzed.Results:The most common symptoms included weakness or numbness of the limbs (67.5%, 108/160), unstable gait (30%, 48/160) and vertigo (20%, 32/160). Among all, 130 cases (81.3%, 130/160) had myelopathy, with the Japanese Orthopaedic Association (JOA) scores from 4 to 16 (mean JOA scores 13.5±2.5). Cranial neuropathy was involved in 20 cases (12.5%). Radiological findings showed brainstem and/or cervical-medullar in 130 cases (81.3%), syringomyelia in 37 cases (23.1%) and Chiari malformation in 30 cases (18.8%). Computed tomography angiography (CTA) was performed in 90 cases, which showed vertebral artery anomalies in 55 cases (61.0%) and excessive medialized internal carotid artery in 5 cases (5.6%). All cases had no spinal cord or vertebral artery injury. The surgery included posterior occipito-cervical fusion (reducible dislocation, 145 cases), and transoral release followed by posterior fusion (irreducible dislocation, 15 cases). Fifty-seven cases were treated using alternative fixation technique. The average follow-up time was 50.5±22.4 months (range, 24 to 120 months). All of 152 cases (95.0%) achieved solid atlantoaxial fusion; there was no obvious osseous fusion formation on postoperative images in 6 cases (3.8%), but no atlantoaxial instability was found on dynamic radiographs; screw loosening happened in 2 patients (1.2%). Nine patients (5.6%) suffered complications, including 4 cases with recurrent dislocation, 2 screw loosening, 2 cases with bulbar paralysis and 1 wound infection. The mean postoperative JOA was 15.1±1.8 (range, 5-17), and the mean neurological improvement rate was 42.9%±33.3% in the patients with myelopathy.Conclusion:"Sandwich" AAD, a subgroup of AAD, has unique clinical features: earlier onset age and more severe myelopathy. The incidence of bone and vascular malformation is higher. So alternative surgical plan and hybrid fixation should be prepared for this subgroup of AAD.

Early childhood caries (ECC) is not only harmful to children's oral cavity and even the whole body, the government and relevant health departments pay more and more attention to the prevention and treatment of early childhood caries. However, at present, the primary treatment for ECC is the traditional filling therapy. The chronic disease management model can conduct regular testing of chronic non-communicable diseases and their risk factors, and provide long-term and effective professional management to patients by supervision and advice by doctors, nurses and pharmacists. This model has a good effect on slowing down the development of the disease, improving the quality of life of patients and saving public health resources. As a common chronic non-communicable disease, ECC is very suitable for prevention and treatment through chronic disease management. In recent years, chronic disease management models have also been increasingly used in the management of caries. The current common chronic disease management models include the chronic care model, innovative care for chronic condition, and British chronic disease management system models. And above models have certain applications in the management of ECC. How to establish the caries risk assessment system suitable for the diagnosis and treatment model of our country, and how to screen the children with high risk of caries by step-by-step prevention and control network for personalized prevention needed to be further studied in the future.

Objective:To compare the short-term outcomes of femoral neck system (FNS) and dynamic hip screw (DHS) in the treatment of femoral neck fractures.Methods:A retrospective analysis was performed of the 105 patients with fresh femoral neck fracture who had been treated by FNS fixation from September 2019 to October 2020 or by DHS fixation from January 2018 to October 2020 at Department of Orthopaedics, The Third Hospital Affiliated to Peking University. In the FNS group of 54 cases, there were 18 males and 36 females with a mean age of (60.7±15.2) years; in the DHS group of 51 cases, there were 14 males and 37 females with a mean age of (63.3±13.2) years. The 2 groups were compared in terms of hospital stay, operation time, intraoperative blood loss, incision length, intraoperative fluoroscopy frequency, qualify of reduction, and femoral neck shortening length, Harris hip score and complications at the last follow-up.Results:The 2 groups were comparable due to insignificant differences in their preoperative general data or follow-up time ( P>0.05). In the FNS group, the median operation time [45.0 (40.0, 59.0) min], intraoperative blood loss [30.0 (20.0, 50.0) mL], incision length [4.0 (4.0, 5.0) cm], intraoperative fluoroscopy frequency [10.5 (9.0, 12.0) times] and hospital stay [2.0 (2.0, 4.0) d] were significantly superior to those in the DHS group [72.0 (55.0, 89.0) min, 50.0 (30.0, 50.0) mL, 7.0 (6.0, 8.0) cm, 18.0 (15.0, 19.0) times, and 3.0 (3.0, 6.0) d] (all P<0.05). There were no statistical differences between the 2 groups in quality of reduction, length of femoral neck shortening, failure rate of internal fixation or Harris hip score at the last follow-up ( P>0.05). There were no such surgical complications as deep infection or femoral head necrosis in either of the 2 groups. Conclusions:In the fixation of femoral neck fractures, both FNS and DHS may lead to fine short-term outcomes. However, compared with DHS, FNS exhibits advantages of simplicity, minimal invasion, less surgical trauma and intraoperative fluoroscopy frequency, and reduced operation time and hospital stay.

Objective To explore the effect of CYP2C19 gene polymorphism on clopidogrel plasma concentration, rate of platelet inhibition and safety. Methods We screen the patients who took clopidogrel after PCI in our hospital, according to the inclusion and exclusion criteria. Blood samples were collected on the 6th day after clopidogrel administration. Clopidogrel blood concentration was determine by RP-HPLC. The CYP2C19 genotype was detected by non-amplified immune hybridization. The rate of platelet inhibition was evaluated by the thromboelastogram. The results were analyzed by SPSS 20.0 software. Results A total of 87 patients were recruited, including 46 males and 41 females. Among them, 34 cases were fast metabolism. 38 cases were medium metabolism. 15 cases were slow metabolism. The result showed that there was no significant difference in drug concentration between fast and intermediate metabolism(P=0.667). There was a significant difference in drug concentration between slow metabolism and fast metabolism or medium metabolism(P<0.05). Analysis of variance and chi-square test showed that CYP2C19 gene polymorphism has a significant effect on clopidogrel platelet inhibition rate and safety (P<0.05). Conclusion Guiding clopidogrel clinical medication based on CYP2C19 genotype alone does not necessarily achieve better therapeutic effects. CYP2C19 genotype detection and blood concentration monitoring can be combined to guide the clinical individualized administration of clopidogrel

Pharmacokinetics (PK) is the study of the absorption, distribution, metabolism, and excretion (ADME) processes of a drug. Understanding PK properties is essential for drug development and precision medication. In this review we provided an overview of recent research on PK with focus on the following aspects: (1) an update on drug-metabolizing enzymes and transporters in the determination of PK, as well as advances in xenobiotic receptors and noncoding RNAs (ncRNAs) in the modulation of PK, providing new understanding of the transcriptional and posttranscriptional regulatory mechanisms that result in inter-individual variations in pharmacotherapy; (2) current status and trends in assessing drug-drug interactions, especially interactions between drugs and herbs, between drugs and therapeutic biologics, and microbiota-mediated interactions; (3) advances in understanding the effects of diseases on PK, particularly changes in metabolizing enzymes and transporters with disease progression; (4) trends in mathematical modeling including physiologically-based PK modeling and novel animal models such as CRISPR/Cas9-based animal models for DMPK studies; (5) emerging non-classical xenobiotic metabolic pathways and the involvement of novel metabolic enzymes, especially non-P450s. Existing challenges and perspectives on future directions are discussed, and may stimulate the development of new research models, technologies, and strategies towards the development of better drugs and improved clinical practice.

Objective:To screen epitope mimics to lipoteichoic acid from a random 12-mer phage display peptide library and i-dentify the specificity of the mimotopes of LTA.Methods:The monoclonal antibody against LTA was used as a target to screen the 12-mer phage display peptide library and the specificity of phage clones were identified by sandwich ELISA.The amino acid sequences of positive phage clones were deduced from DNA sequencing.The specificity of synthetic peptide were identified by sandwich ELISA.Results:4 clones were obtained after 3 rounds of screening.Amino acid sequence analysis revealed four different types of mimotope sequence.A linear peptide (GHxDFRQxxQPS),named L2,which derived from positive sequence was synthesized.ELISA result indicates that L2 can bind to anti-LTA mAb specifically in a dose-dependent manner.Conclusion:The mimotopes of LTA were obtained by using the phage display technology.

Aim To detect the role of sirtuin1 ( SIRT1 ) in hepatotoxity caused by valproic acid ( VPA) . Methods The changes of SIRT1 expression of HepG2 cells were detected by Western blot. And then SIRT1 plasmid or siRNA was transfected to con-struct SIRT1 overexpressed or knocked-down HepG2 cells. Furthermore, SRB assays were taken to observe the changes of viability of these cells exposed to VPA. Results VPA suppressed SIRT1 expression in a time and dose-dependent manner. SIRT1 overexpression showed a protective effect to the cytotoxicity caused by VPA, and the IC50 before and after transfection was (4. 025 ± 0. 47) and (10. 87 ± 1. 50) mmol·L-1 re-spectively. Moreover, transfection of SIRT1 siRNA sensitized HepG2 cells to VPA, and the IC50 before and after transfection was (1. 938 ± 0. 16) and (0. 663 ± 0. 05) mmol·L-1 respectively. Conclusion VPA suppressed SIRT1 expression in HepG2 cells and over-expression of SIRT1 could reduce cytotoxicity induced by VPA.