ObjectiveTo investigate the efficacy of sequential tenofovir alafenamide fumarate （TAF） therapy versus the regimen of entecavir （ETV） combined with TAF in chronic hepatitis B （CHB） patients experiencing low-level viremia （LLV） after ETV therapy， as well as their impact on virologic response， liver and renal function， and blood lipid levels. MethodsA total of 217 CHB patients with LLV after ETV treatment who were admitted to Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine from May 2020 to December 2023 were enrolled， and according to the treatment regimen， they were divided into TAF group （180 patients receiving sequential TAF therapy） and combined group （37 patients receiving ETV+TAF therapy）. The propensity score matching （PSM） method was used to match the patients at a ratio of 1∶1， and finally 37 patients were included in each group to balance the baseline confounding factors. The two groups were compared in terms of hepatitis B virus DNA （HBV DNA） clearance rate， hepatitis B envelope antigen （HBeAg） clearance rate， liver and renal function parameters （liver stiffness measurement ［LSM］， platelet count ［PLT］， aspartate aminotransferase ［AST］， alanine aminotransferase ［ALT］， and creatinine ［Cr］）， blood lipid levels （total cholesterol ［TC］， triglyceride ［TG］， high-density lipoprotein cholesterol ［HDL-C］， and low-density lipoprotein cholesterol ［LDL-C］）， and the incidence rate of adverse reactions. The independent samples t-test was used for comparison of normally distributed continuous data between two groups， and the paired t-test was used for comparison within each group； the chi-square test was used for comparison of categorical data between groups. ResultsAfter 48 weeks of treatment， compared with the TAF group， the combined group had significantly higher HBV DNA clearance rate （86.49% vs 59.46%， χ²=6.852， P=0.009） and HBeAg clearance rate （59.46% vs 35.14%， χ²=4.391， P=0.036）. After treatment， compared with the TAF group， the combined group had significantly lower levels of LSM （7.01±1.50 kPa vs 7.90±1.68 kPa， t=2.404， P=0.019）， AST （18.02±2.28 U/L vs 21.12±2.85 U/L， t=5.166， P<0.001）， and ALT （19.85±3.86 U/L vs 22.00±3.90 U/L， t=2.383， P=0.020） and significantly higher levels of PLT ［（218.35±42.60）×10⁹/L vs （192.82±44.13）×10⁹/L， t=2.532， P=0.014］ and Cr （70.92±6.54 μmoL/L vs 67.60±6.13 μmoL/L， t=2.253， P=0.027）. After treatment， there was a slight increase in the level of TC in both the TAF group （5.60±0.89 mmol/L vs 5.18±0.85 mmol/L， t=2.076， P=0.041） and the combined group （5.45±0.80 mmol/L vs 5.02±0.83 mmol/L， t=2.269， P=0.026）. There was no significant difference in the incidence rate of adverse reactions between the TAF group and the combined group （21.62% vs 18.92%， χ²=0.084， P=0.772）. ConclusionFor ETV-treated CHB patients experiencing LLV， compared with sequential TAF therapy， the ETV+TAF combined therapy can effectively increase virologic response rate， alleviate liver fibrosis， and improve liver function， whereas sequential TAF therapy has less impact on renal function. Sequential or combined therapy with TAF may induce a slight increase in the level of TC， which should be taken seriously in clinical practice.

OBJECTIVE To investigate the establishment and promotion of a new standardized management model for anti- osteoporosis medication after fragility fracture surgery by resident clinical pharmacists， and provide references for resident pharmacists to carry out clinical pharmaceutical services. METHODS From July 2023 to March 2024，595 post-brittle fracture surgery patients were enrolled. Using the PDCA （plan-do-check-act） cycle，resident clinical pharmacists identified issues and conducted investigations in clinical practice. Through integrating clinical pharmacist intervention services before， during and after treatment， a medication treatment pathway was developed， thereby establishing a standardized management model for anti- osteoporosis treatment following fragility fracture surgery. Leveraging the National Brittle Fracture Big Data Platform （under the National Clinical Research Center for Orthopedics and Sports Rehabilitation）， a dedicated data module was constructed， providing big data support to evaluate the efficacy of this pharmaceutical care model. RESULTS Continuous PDCA cycle driven improvements significantly increased the proportion of osteoporosis diagnosis （from 9% before intervention to 81%） and proportion of drug treatment （from 4% to 75%）.The proportions of bone density and bone metabolism testing also rose markedly，positively impacting long-term patient outcomes. CONCLUSIONS The establishment of a standardized management model for anti- osteoporosis treatment following fragility fracture surgery by resident clinical pharmacists has enhanced clinicians’ diagnostic and therapeutic capabilities for osteoporosis， ensures rational medication use in osteoporosis patients， and demonstrates significant potential for widespread adoption and application.

In a healthy human, the airway mucus forms a thin, protective liquid layer covering the surface of the respiratory tract. It comprises a complex blend of mucin, multiple antibacterial proteins, metabolic substances, water, and electrolytes. This mucus plays a pivotal role in the lungs' innate immune system by maintaining airway hydration and capturing airborne particles and pathogens. However, heightened mucus secretion in the airway can compromise ciliary clearance, obstruct the respiratory tract, and increase the risk of pathogen colonization and recurrent infections. Consequently, a thorough exploration of the mechanisms driving excessive airway mucus secretion is crucial for establishing a theoretical foundation for the eventual development of targeted drugs designed to reduce mucus production. Across a range of lung diseases, excessive airway mucus secretion manifests with unique characteristics and regulatory mechanisms, all intricately linked to mucin. This article provides a comprehensive overview of the characteristics and regulatory mechanisms associated with excessive airway mucus secretion in several prevalent lung diseases.
Humans ; Mucus/metabolism* ; Mucins/physiology* ; Lung Diseases/metabolism* ; Respiratory Mucosa/metabolism* ; Pulmonary Disease, Chronic Obstructive/physiopathology* ; Asthma/physiopathology* ; Cystic Fibrosis/physiopathology* ; Mucociliary Clearance/physiology*

OBJECTIVES: To evaluate the application value of genetic newborn screening (gNBS) in the Yunnan region. METHODS: A prospective study was conducted with a random selection of 3 001 newborns born in the Yunnan region from February to December 2021. Traditional newborn screening (tNBS) was used to test biochemical indicators, and targeted next-generation sequencing was employed to screen 159 genes related to 156 diseases. Positive-screened newborns underwent validation and confirmation tests, and confirmed cases received standardized treatment and long-term follow-up. RESULTS: Among the 3 001 newborns, 166 (5.53%) were initially positive for genetic screening, and 1 435 (47.82%) were genetic carriers. The top ten genes with the highest variation frequency were GJB2 (21.29%), DUOX2 (7.27%), HBA (6.14%), GALC (3.63%), SLC12A3 (3.33%), HBB (3.03%), G6PD (2.94%), SLC25A13 (2.90%), PAH (2.73%), and UNC13D (2.68%). Among the initially positive newborns from tNBS and gNBS, 33 (1.10%) and 47 (1.57%) cases were confirmed, respectively. A total of 48 (1.60%) cases were confirmed using gNBS+tNBS. The receiver operating characteristic curve analysis demonstrated that the areas under the curve for tNBS, gNBS, and gNBS+tNBS in diagnosing diseases were 0.866, 0.982, and 0.968, respectively (P<0.05). DeLong's test showed that the area under the curve for gNBS and gNBS+tNBS was higher than that for tNBS (P<0.05). CONCLUSIONS gNBS can expand the range of disease detection, and its combined use with tNBS can significantly shorten diagnosis time, enabling early intervention and treatment.
Humans ; Infant, Newborn ; Neonatal Screening ; Genetic Testing ; Female ; Male ; Follow-Up Studies ; Prospective Studies ; China

Geriatric oral health care encounters significant challenges with the increase in the proportion of older individuals. Age-related changes in the dentition, muscles, and joints result in a decline in objective masticatory function, subjective restoration requirements, and acceptability among the elderly population, with individual variations influenced by systemic health. Considering functional requirements, the adaptability of stomatognathic and systemic health conditions, health economics and other factors, the authors believe that it should not be limited to the conventional "one-to-one" strategy for replacing missing teeth in geriatric prosthodontics. There is an urgent need for a precise and adaptable restoration strategy that is more suitable for older individuals. The proposal of a new concept of functional tooth loss updates the minimal restoration standards for elderly patients and establishes the theory of age-friendly functional restoration. Based on the restoration strategy of functional tooth loss, this paper proposes a new concept termed "age-friendly functional restoration of the stomatognathic system", which integrates treatment considerations including endodontics, periodontology, mucosa, muscles, temporomandibular joint, and systemic health. Efforts should be made in four areas as follows. Firstly, the "assessment of accessible function" should be enhanced by considering the interrelationship between stomatognathic and systemic health. Secondly, the "evaluation of appropriate function" is supposed to be optimised in view of subjective needs and objective evaluation of the stomatognathic system. Moreover, the "formulation of treatment plans" needs to be accomplished with the aid of assistive technologies, such as artificial intelligence, to accurately exert appropriate functional restoration. Lastly, the "management and maintenance of health" is likely to be strengthened through follow-ups, propaganda and education, and preventive healthcare, so as to improve quality of life and ultimately achieve healthy ageing among older individuals.
Humans ; Tooth Loss/therapy* ; Aged ; Stomatognathic System ; Oral Health ; Dental Care for Aged ; Dental Restoration, Permanent/methods*

Objective:To explore the dosimetric characteristics of intensity modulated proton therapy (IMPT), intensity modulated radiation therapy (IMRT) and tomotherapy (TOMO) techniques applied in the irradiation of pediatric whole central nervous system tumors.Methods:Taking the target area of a 14-year-old pediatric patient clinically diagnosed with atypical teratoid/rhabdomyoid tumor, meningeal metastasis by Shandong Cancer Hospital and Institute, and undergoing craniospinal irradiation (CSI) as an example, IMPT, IMRT and TOMO plans were designed respectively based on the clinical prescription of the target area and the limit requirements of organs at risk (OARs). The conformal index (CI), homogeneity index (HI) and gradient index (GI) of each planning target volume, as well as the dose volume index of normal tissues, were evaluated to compare the dosimetric characteristics of the three types of plans.Results:The CI (0.71), HI (0.05) and GI (3.13) of the IMPT plan were comparable to those of IMRT plan (0.80, 0.08, 3.14). The HI (0.03) and GI (2.54) of the TOMO plan were excellent, which were all within the clinically acceptable range. The irradiation dose to parallel organs in the IMPT plan was lower than that in the IMRT and TOMO plan. In the IMPT plan, V 5 of lungs was 2.9%, IMRT plan was 37.6%, and TOMO plan was 43.5%. The D mean of liver in the IMPT plan was 0.01 Gy (RBE), IMRT plan was 6.12 Gy, and TOMO plan was 6.39 Gy. In the IMPT plan, none of the bladder, rectum, and femoral head received the dose, while there was low-dose radiation in both IMRT and TOMO plan. For serial organs adjacent to and within the target area, the D max of spinal cord and brainstem in IMPT plan was 39.89 and 39.88 Gy (RBE), respectively; in IMRT plan, they were 39.43 and 38.59 Gy, respectively; and in TOMO plan, they were 38.41 and 37.69 Gy, respectively. The low-dose area in the IMPT plan was significantly better than the photon radiotherapy plans. Among them, the absolute volume IMPT plan occupied by 10% of the prescribed dose area in the patient's body was reduced by 70.10% compared with IMRT plan and 76.96% compared with TOMO plan; the 30% prescribed dose volume IMPT plan was reduced by 53.49% compared with IMRT plan and 62.51% compared with TOMO plan; the 50% prescribed dose volume IMPT plan was reduced by 39.06% compared with IMRT plan and 42.23% compared with TOMO plan. Conclusions:The IMPT plan demonstrated significantly reduced low-dose exposure and lower doses to parallel OARs compared to both IMRT and TOMO plans in pediatric CSI. The CI, HI and GI of the three plans can all meet the clinical requirements. However, for serial organs adjacent to and within the target area, the D max of the IMPT plan may be higher than that of IMRT and TOMO plans.

Objective:To investigate the dosimetric characteristics of intensity modulated proton therapy (IMPT) and photon volumetric modulated arc therapy (VMAT) in typical head and neck malignant tumors.Methods:Three types of typical head and neck tumors (nasopharyngeal carcinoma, parotid gland carcinoma, laryngeal carcinoma) treated at Shandong Cancer Hospital and Institute from December 2023 to December 2024 were taken as research subjects. IMPT and VMAT radiotherapy plans were created according to clinical prescription requirements of target and organs at risk limits respectively. The conformity index (CI), homogeneity index (HI) and gradient index (GI) for target coverage of two radiotherapy plans were evaluated for 3 patients, as well as the dosimetric indicators of organs at risk.Results:The CI of IMPT for nasopharyngeal carcinoma, parotid gland carcinoma and laryngeal carcinoma were 0.70, 0.72 and 0.67, respectively. The HI were 0.11, 0.08 and 0.08, respectively. The GI were 3.08, 2.49 and 3.75, respectively. The CI of VMAT plans were 0.77, 0.82 and 0.91, respectively. The HI were 0.12, 0.10 and 0.04, respectively. The GI were 3.67, 2.63 and 3.45, respectively. The results showed that CI of IMPT plan was slightly lower than that of VMAT plan, and HI of IMPT plan was comparable to that of VMAT plan, the GI of the IMPT plan for patients with nasopharyngeal carcinoma and parotid gland carcinoma was lower than that of the VMAT plan, and the GI of the IMPT plan for patient with laryngeal carcinoma was higher than that of the VMAT plan, and all were within the clinically acceptable range. The IMPT plan has demonstrated significant dose advantages in the treatment of nasopharyngeal carcinoma, parotid gland carcinoma and laryngeal carcinoma. For patient with nasopharyngeal carcinoma, the IMPT plan reduced the D max of the left and right crystals by 54.1% and 50.4%, respectively, compared to VMAT plan, and reduced the D mean of the oral and laryngeal tissues by 40.5% and 49.6%, respectively. For patient with parotid gland carcinoma, IMPT plan reduced the D max of the brainstem and spinal cord by 66.2% and 40.5%, respectively, compared to VMAT plan. For patient with laryngeal carcinoma, IMPT reduced spinal cord D max by 77.0%, while thyroid cartilage D mean increased by 8.0% compared to VMAT plan. For the additional dose in the patients' body, taking the absolute volumes occupied by the prescribed dose areas of 10%, 30%, and 50% in the patients' body as examples, IMPT plan of nasopharyngeal carcinoma patient decreased by 29.7%, 29.6%, and 34.9% compared to VMAT plan, respectively. IMPT plan of parotid gland carcinoma patient decreased by 61.0%, 39.7%, and 17.4% compared to VMAT plan, respectively. IMPT plan of laryngeal carcinoma patient decreased by 63.9%, 31.7%, and 4.1% compared to VMAT plan, respectively. Conclusions:Compared with VMAT plan, IMPT plan can effectively reduce the irradiation dose of most organs at risk near the target of head and neck tumors, but the dose of string organs close to the target area may be higher, which needs attention.

Objective Aedes albopictus is the primary vector of the dengue virus.Screening and the analysis of immune-related genes in DENV2-infected Ae.albopictus provides a scientific basis for further research on blocking the extrinsic incubation period of the dengue virus.Methods Through the approach of literature mining,thirty-three potential immune-related genes were screened from species such as Aedes aegypti and Anopheles gambiae,which have a close genetic relationship with Ae.albopictus.The protein—protein interaction(PPI)analysis is employed to explore the interaction relationship of the proteins encoded by genes.The alterations in mRNA expression levels of the relevant genes in DENV2-infected Ae.albopictus midgut were detected using the qRT-PCR method.Results The PPI results indicates that TLR and Spz of Ae.albopictus;Rel1,Rel2,DefC,Spz,PIWI,Ago2,DOME and HOP of Ae.aegypti;and Rel1,Rel2,CACT,STAT and DOME of An.gambiae exhibit PPI relationships.After Ae.albopictus was infected with DENV2,10 genes showed significant difference in expression.Ago3(7.39,P<0.05),DOMEa(1.63,P<0.01),DOMEb(21.29,P<0.001),and TLRb(1.61,P<0.05)were significantly up-regulated.Rel1(0.62,P<0.001),CACTl(0.65,P<0.001),Rel2a(0.65,P<0.01),Rel2b(0.24,P<0.001),GATAa(0.64,P<0.01)and DefC(0.28,P<0.05)were significantly down-regulated.Conclusions The concordance of Ae.albopictus with Ae.aegypti was higher than that with An.gambiae.DOMEb,Ago3,Rel2b and DefC,can serve as the preferred target genes for subsequent studies on DENV2 immune blockade.

Objective:To explore the role of mechanical hemodynamic support (MHS) in mapping and catheter ablation of patients with hemodynamically unstable ventricular tachycardia (VT), report single-center experience in a cohort of consecutive patients receiving VT ablation during MHS therapy, and provide evidence-based medical evidence for clinical practice.Methods:This was a retrospective cohort study. Patients with hemodynamically unstable VT who underwent catheter ablation with MHS at Beijing Anzhen Hospital, Capital Medical University between August 2021 and December 2023 were included. Patients were divided into rescue group and preventive group according to the purpose of treatment. Their demographic data, periprocedural details, and clinical outcomes were collected and analyzed.Results:A total of 15 patients with hemodynamically unstable VT were included (8 patients in the rescue group and 7 patients in the preventive group). The acute procedure was successful in all patients. One patient in the rescue group had surgical left ventricular assist device (LVAD) implantation, remaining 14 patients received extracorporeal membrane oxygenation (ECMO) for circulation support. ECMO decannulation was performed in 12 patients due to clinical and hemodynamic stability, of which 6 patients were decannulation immediately after surgery and the remaining patients were decannulation at 2.0 (2.5) d after surgery. Two patients in the rescue group died during the index admission due to refractory heart failure and cerebral hemorrhage. During a median follow-up of 30 d (1 d to 12 months), one patient with LVAD had one episode of ventricular fibrillation at 6 months after discharge, and no further episodes of ventricular fibrillation and/or VT occurred after treatment with antiarrhythmic drugs. No malignant ventricular arrhythmia occurred in the remaining 12 patients who were followed up.Conclusions:MHS contributes to the successful completion of mapping and catheter ablation in patients with hemodynamically unstable VT, providing desirable hemodynamic status for emergency and elective conditions.

The first patient,a 10-year-old girl,presented with pancytopenia and recurrent epistaxis,along with a history of repeated upper respiratory infections,café-au-lait spots,and microcephaly.Genetic testing revealed compound heterozygous mutations in the DNA ligase Ⅳ(LIG4)gene,leading to a diagnosis of LIG4 syndrome.The second patient,a 6-year-old girl,was seen for persistent thrombocytopenia lasting over two years and was noted to have short stature,hyperpigmented skin,and hand malformations.She had a positive result from chromosome breakage test.She was diagnosed with Fanconi anemia complementation group A.Despite similar clinical presentations,the two children were diagnosed with different disorders,suggesting that children with hemocytopenia and malformations should not only be evaluated for hematological diseases but also be screened for other potential underlying conditions such as immune system disorders.[Chinese Journal of Contemporary Pediatrics,2024,26(4):410-4131