OBJECTIVE To conduct a comprehensive clinical evaluation of four nucleoside （acid） analogues that have been approved and marketed in China， such as entecavir， tenofovir disoproxil fumarate， tenofovir alafenamide fumarate， and tenofovir amibufenamide. METHODS According to the Guideline for the Administration of Clinical Comprehensive Evaluation of Drugs （2021 edition， trial implementation）， a comprehensive search was conducted across databases including CNKI， Wanfang Data， VIP， PubMed， the Cochrane Library， Embase， as well as relevant official websites. Drug package inserts， guidelines， consensus statements， and relevant literature for the four drugs were collected and subjected to a comprehensive evaluation across six dimensions： safety， efficacy， cost-effectiveness， innovativeness， suitability， and accessibility. RESULTS The scores for entecavir in terms of safety， efficacy， cost-effectiveness， innovativeness， suitability， and accessibility-along with its comprehensive score-were 13， 14， 13， 10， 18， and 6， totaling 74 points. For tenofovir disoproxil fumarate， the respective scores were 13， 17， 18， 8， 18， and 7， totaling 81 points. For tenofovir alafenamide fumarate， the scores were 14， 20， 12， 8， 18， and 5， totaling 77 points. Finally， for tenofovir amibufenamide， the scores were 10.5， 17， 10， 6， 15， and 4， totaling 62.5 points. CONCLUSIONS Tenofovir disoproxil fumarate， with the highest score， is recommended as the first-line option， suitable for adults， children， and pregnant women. However， caution is warranted for potential renal impairment. Tenofovir alafenamide fumarate is recommended as a second-line alternative， particularly for individuals at high risk for bone and renal damage. Entecavir has a score similar to tenofovir alafenamide fumarate but requires dosing on an empty stomach and dose adjustment based on renal function of patients. Tenofovir amibufenamide received the lowest score and is considered a weak recommendation. The clinical application of these nucleoside （acid） analogues should be individualized based on the patient’s age， physiological status， and risk factors.

Objective:To investigate the molecular characteristics and clinical heterogeneity of Usher syndrome（USH） -related gene variants in patients with hereditary hearing loss in southwest China, providing a basis for early diagnosis and clinical management. Methods:Thirteen patients from twelve families with hearing loss who attended the Affiliated Children's Hospital of Kunming Medical University between January 2017 and March 2021 were enrolled. All patients were identified as carrying USH-related gene variants through next-generation sequencing. Sanger sequencing was performed for all patients and their parents to validate the pathogenic variants. Comprehensive clinical evaluations, including medical history collection, otologic and ophthalmologic examinations, and vestibular function assessments, were conducted. Results:Among the 13 patients, 4 were diagnosed with USH type 1 and 2 with USH type 2. A total of 19 pathogenic or likely pathogenic variants were detected in USH-related genes, including MYO7A,CDH23,USH1C, and USH2A. The causative gene was MYO7A in 3 probands, CDH23 in 5, USH1C in 3, and USH2Ain 2. All patients exhibited an autosomal recessive inheritance pattern. Vestibular dysfunction was observed in 4 patients, and retinitis pigmentosa（RP） in 3 patients. Based on the genotype-phenotype correlation, 6 patients were initially diagnosed with USH, while 7 were classified as having non-syndromic hearing loss（NSHL）. Conclusion:This study revealed the clinical heterogeneity of USH-related gene variants in patients with hereditary deafness in southwest China. Although the clinical manifestations of USH are complex and there are overlapping characteristics between different subtypes, genetic testing provides an important basis for early diagnosis and precise clinical management. Especially for those with typical hearing loss, early genetic diagnosis can provide a window of time for early detection and intervention of retinitis pigmentosa.
Humans ; Usher Syndromes/genetics* ; Myosin VIIa ; Phenotype ; Male ; Female ; Myosins/genetics* ; Mutation ; Cadherins/genetics* ; Child ; Extracellular Matrix Proteins/genetics* ; Adolescent ; Pedigree ; High-Throughput Nucleotide Sequencing ; Cadherin Related Proteins ; Cytoskeletal Proteins ; Cell Cycle Proteins

Cantharidin (CTD), a natural compound used to treat multiple tumors in the clinic setting, has been limited due to acute kidney injury (AKI). However, the major cause of AKI and its underlying mechanism remain to be elucidated. Serum creatinine (SCr) and blood urea nitrogen (BUN) were detected through pathological evaluation after CTD (1.5 mg/kg) oral gavage in mice in 3 days. Kidney lipidomics based on ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) was used to investigate lipids disorder after CTD exposure in mice. Then, spatial metabolomics based on matrix-assisted laser desorption/ionization-mass spectrometry imaging (MALDI-MSI) was used to detect the kidney spatial distribution of lipids. Integrative analysis was performed to reveal the spatial lipid disorder mechanism and verify key lipids in vitro. The results showed that the levels of SCr and BUN were increased, and tubular necrosis was observed in mouse kidneys, resulting in acute tubular necrosis (ATN) in CTD-induced AKI. Then, lipidomics results revealed that after CTD exposure, 232 differential lipid metabolites and 11 pathways including glycerophospholipid (GP) and sphingolipid (SL) metabolism were disrupted. Spatial metabolomics revealed that 55 spatial differential lipid metabolites and nine metabolic pathways were disturbed. Subsequently, integrative analysis found that GP metabolism was stimulated in the renal cortex and medulla, whereas SL metabolism was inhibited in the renal cortex. Up-regulated lysophosphatidylcholine (LysoPC) (18:2(9Z,12Z)), LysoPC (16:0/0:0), glycerophosphocholine, and down-regulated sphingomyelin (SM) (d18:0/16:0), SM (d18:1/24:0), and SM (d42:1) were key differential lipids. Among them, LysoPC (16:0/0:0) was increased in the CTD group at 1.1196 μg/mL, which aggravated CTD-induced ATN in human kidney-2 (HK-2) cells. LysoPC acyltransferase was inhibited and choline phosphotransferase 1 (CEPT1) was activated after CTD intervention in mice and in HK-2 cells. CTD induces ATN, resulting in AKI, by activating GP metabolism and inhibiting SL metabolism in the renal cortex and medulla, LysoPC (16:0/0:0), LysoPC acyltransferase, and CEPT1 may be the therapeutic targets.

PET of molecular imaging plays a pivotal role in Alzheimer's disease(AD)by visualizing and quantifying amyloid β(Aβ)deposition,phosphorylated tau protein(T)and glucose metabolism,having important value in the entire process of diagnosis and treatment of AD.The applications of PET multimodal imaging in AD were systematically reviewed in this article,in order to advance precision diagnosis,treatment and scientific management of AD.

Objective:To analyze the distribution and epidemiological characteristics of common non-bacterial pathogens in hospitalized children with acute respiratory tract infections(ARTI)from a multi-center study covering 4 regions in Fujian Province in 2023.Methods:A retrospective cohort study was conducted using medical record analysis.A total of 22 769 hospitalized children with ARTI were enrolled from January to December 2023 across seven regional pediatric medical centers in Fujian Province (covering four major geographical divisions of Fuzhou, Nanping, Sanming and Longyan; all selected hospitals were regional children′s medical centers).Using single-tube multiplex PCR with fragment analysis on a Sanger sequencing platform, the nucleic acids of 11 common non-bacterial respiratory pathogens were tested in nasopharyngeal swabs collected from 22 769 children. These pathogens included influenza A virus(FluA), influenza B virus(FluB), parainfluenza virus(PIV), respiratory syncytial virus (RSV), adenovirus (ADV), human rhinovirus (HRV), human bocavirus (HBoV), human coronavirus (HCoV), human metapneumovirus(HMPV), Mycoplasma pneumoniae(MP), and Chlamydia (Ch). Count data were described as [ n(%)], and the chi-square test/Fisher′s exact test was used to compare the differences in rates between groups. Epidemiological features, including positive detection rates, pathogen profiles, and correlations with region, sex, age and month, were analyzed. Results:Among 22 769 children with ARTI, pathogens were detected in 16 213 cases (71.21%), including 13 340 single infections (58.59%).The detection rates of single pathogens in descending order were human rhinovirus (HRV, 12.95%), Mycoplasma pneumoniae(MP, 12.27%), respiratory syncytial virus(RSV, 11.12%), influenza A virus (Flu-A, 7.98%), parainfluenza virus(PIV, 4.66%), human metapneumovirus(HMPV, 4.60%), adenovirus(ADV, 2.70%), human bocavirus(HBoV, 0.84%), human coronavirus(HCoV, 0.82%), influenza B virus(Flu-B, 0.47%) and Chlamydia(Ch, 0.18%).Mixed infections occurred in 2 873 cases(12.62%), primarily dual infections(2 679 cases).Regional analysis revealed significant disparities:Luoyuan County Hospital (Fuzhou) exhibited the highest total detection rate(86.59%, 1 414/1 633)and mixed infection rate(23.27%, 380/1 633)(both P<0.001), with notably elevated MP (26.39%, 431/1 633);Jian′ou City Hospital(Nanping) ranked second for Flu-A(14.21%, 409/2 879), RSV(13.20%, 380/2 879) and mixed infections(17.12%, 493/2 879);Lianjiang County Hospital(Fuzhou) showed distinct prevalence of Flu-A(10.68%, 130/1 217), PIV(6.00%, 73/1 217), and HBoV(1.73%, 21/1 217); Yong′an City Hospital (Sanming) reported high MP (26.07%, 238/913) and RSV(12.38%, 113/913);Shaowu City Hospital(Nanping) was dominated by MP (18.60%, 407/2 188) and HRV(13.39%, 293/2 188); Tingzhou Hospital(Longyan) had the highest HRV (17.88%, 407/2 276) and Flu-B (0.75%, 17/2 276); and Fuzhou Children′s Hospital showed elevated ADV(3.38%, 394/11 663) and HCoV(1.08%, 126/11 663). Except for Flu-B(0.47%, 108/22 769; P=0.054) and Ch(0.18%, 40/22769; P=0.900), all pathogens and mixed infections exhibited significant regional variations ( P<0.05).Gender analysis indicated higher detection rates of HRV, RSV, Flu-A, ADV, PIV, HBoV and mixed infections in males, while MP, HMPV, Flu-B, HCoV, and Ch were more prevalent in females, with statistically significant differences for HRV and MP (both P<0.001). Age stratification showed the highest overall detection rate in the 3-<6 years group (75.48%; P<0.001): RSV and Ch peaked in infants (<1 year), HRV, PIV, ADV and HBoV in toddlers (1-<3 years), HMPV, HCoV, and mixed infections in preschool children (3-<6 years), and MP, Flu-A and Flu-B in older children (6-<18 years).Analyzing the prevalent months, the monthly prevalence trends of pathogens in various regions are similar.Seasonal trends demonstrated year-round HRV activity (peaking in spring/autumn), MP prevalence in autumn/winter, RSV surges in spring-summer (April-June) and late summer-autumn (August-October), and Flu-A predominanced in winter-spring. Conclusion:Multiplex PCR with fragment analysis demonstrated high diagnostic efficacy. The top 4 non-bacterial pathogens in Fujian Province′s ARTI-hospitalized children in 2023 were HRV, MP, RSV and Flu-A. Pathogen distribution exhibited significant regional, age and seasonal variations, emphasizing the need for targeted prevention strategies.

Cantharidin(CTD),a natural compound used to treat multiple tumors in the clinic setting,has been limited due to acute kidney injury(AKI).However,the major cause of AKI and its underlying mechanism remain to be elucidated.Serum creatinine(SCr)and blood urea nitrogen(BUN)were detected through pathological evaluation after CTD(1.5 mg/kg)oral gavage in mice in 3 days.Kidney lipidomics based on ultra-high performance liquid chromatography-tandem mass spectrometry(UPLC-MS/MS)was used to investigate lipids disorder after CTD exposure in mice.Then,spatial metabolomics based on matrix-assisted laser desorption/ionization-mass spectrometry imaging(MALDI-MSI)was used to detect the kidney spatial distribution of lipids.Integrative analysis was performed to reveal the spatial lipid disorder mechanism and verify key lipids in vitro.The results showed that the levels of SCr and BUN were increased,and tubular necrosis was observed in mouse kidneys,resulting in acute tubular necrosis(ATN)in CTD-induced AKI.Then,lipidomics results revealed that after CTD exposure,232 differential lipid metabolites and 11 pathways including glycerophospholipid(GP)and sphingolipid(SL)metabolism were disrupted.Spatial metabolomics revealed that 55 spatial differential lipid metabolites and nine metabolic pathways were disturbed.Subsequently,integrative analysis found that GP metabolism was stimulated in the renal cortex and medulla,whereas SL metabolism was inhibited in the renal cortex.Up-regulated lysophosphatidylcholine(LysoPC)(18∶2(9Z,12Z)),LysoPC(16∶0/0∶0),glycerophosphocholine,and down-regulated sphingomyelin(SM)(d18∶0/16:0),SM(d 18∶1/24:0),and SM(d42∶1)were key differential lipids.Among them,LysoPC(16∶0/0∶0)was increased in the CTD group at 1.1196 μg/mL,which aggravated CTD-induced ATN in human kidney-2(HK-2)cells.LysoPC acyltransferase was inhibited and choline phos-photransferase 1(CEPT1)was activated after CTD intervention in mice and in HK-2 cells.CTD induces ATN,resulting in AKI,by activating GP metabolism and inhibiting SL metabolism in the renal cortex and medulla,LysoPC(16:0/0:0),LysoPC acyltransferase,and CEPT1 may be the therapeutic targets.

Objective:To investigate the effect of CT-derived fractional flow reserve (CT-FFR) measurement sites on the values and the diagnostic performance, and to determine the optimal measurement site for CT-FFR using invasive FFR as the reference standard.Methods:This study was part of the CT-FFR CHINA clinical trial. Patients with suspected coronary artery disease who were scheduled for invasive coronary angiography (ICA) were prospectively recruited from five clinical centers across the country from November 2018 to March 2020. Each enrolled patient underwent coronary CT angiography (CCTA), CT-FFR, ICA, and invasive pressure wire-based FFR assessments sequentially within one week. Four groups of CT-FFR values were obtained on each enrolled target vessels according to different CT-FFR measurement locations: 1, 2, 3 cm distal to the target lesion, and terminal vessel groups. Spearman and Bland-Altman analyses were used to explore the correlation and consistency of CT-FFR values and FFR values at different measurement sites. The measurement deviation of CT-FFR was also compared. Diagnostic accuracy and performance of CT-FFR, including sensitivity, specificity, positive predictive value, negative predictive value, and area under the receiver operating characteristic curve (AUC), in discriminating myocardial ischemia were analyzed across all measurement site groups on a per-vessel level, using FFR as the reference standard.Results:A total of 289 patients with 345 target lesion vessels were included. According to CCTA, there were 51 target vessels (14.8%) with<50% stenosis, 106 vessels (30.7%) with 50%-69% stenosis, and 188 vessels (54.5%) with stenosis≥70%. At per-vessel level, CT-FFR and FFR values at each measurement position group were highly positively correlated: 1 cm distal to target lesion group, r=0.734 ( P<0.001); 2 cm distal to target lesion group, r=0.732 ( P<0.001); 3 cm distal to target lesion group, r=0.737 ( P<0.001); terminal vessel group was 0.719 ( P<0.001). At per-vessel level, CT-FFR and FFR values of all measurement sites were in good agreement (Bland-Altman analysis results): 1 cm distal to target lesion group, 0.014 (95% LoA 0.002-0.026); 2 cm distal to target lesion group, 0.026 (95% LoA 0.015-0.038); 3 cm distal to target lesion group, 0.040 (95% LoA 0.039-0.051); terminal vessel group, 0.075 (95% LoA 0.064-0.087). And at per-vessel level, the accuracy of diagnosing myocardial ischemia with CT-FFR at 1 cm was highest [84.6% (95% CI 80.4%-88.3%)], and the lowest accuracy in the terminal vessel group [67.0% (95% CI 61.7%-72.0%)]. However, there was no significant difference in the diagnostic accuracy of CT-FFR at 1 cm, 2 cm [80.6% (95% CI 76.1%-84.6%)] and 3 cm [77.5% (95% CI 72.6%-81.7%)]. AUC of CT-FFR at 1 cm distal to the lesion were both highest for global level and moderately stenosis (50%-69%) lesions [0.85 (95% CI 0.81-0.89), 0.84 (95% CI 0.77-0.90)]. And the differences were statistically significant among the four measurement location groups (all P<0.05). Conclusions:The deviation of CT-FFR increases with measurement site distance distal to target lesions. One centimeter distal to the target lesion is the optimal measurement site, and the CT-FFR value here shows the highest diagnostic performance for myocardial ischemic lesions, especially for moderate stenosis.

Objective To construct an evidence-based practice program of discharge preparation services for hip replacement patients based on the best evidence,and to evaluate its clinical effects,aiming to provide references for the implementation of relevant interventions.Methods Knowledge to Action Framework was used as a guide to summarise the best evidence on discharge preparation services for hip replacement patients and to select services based on clinical context.We selected 38 hip replacement patients and 17 healthcare professionals from the De-partment of Orthopaedic Surgery at a tertiary A hospital in Shanghai in September-October 2023 to conduct a baseline review,identify facilitating and hindering factors,and develop a practice protocol.We also selected 38 hip replacement patients and 17 healthcare professionals from November-December 2023 on this ward for evidence-based practice.Nurses'rates of completion of review indicators,levels of knowledge of discharge preparation ser-vices,and discharge planning competencies were compared before and after practice.Patients'readiness for dis-charge,hip function,and unplanned readmissions were also compared before and after the practice.Results After evidence-based practice,nurses'completion rates of review indicators,knowledge of discharge preparation services,and discharge planning competencies were higher than baseline levels(P＜0.05).Hip replacement patients showed a significant improvement in readiness for discharge and hip function(P＜0.001).Conclusion The implementation of an evidence-based practice program of discharge preparation services improves nurses'knowledge and skills,and also contributes to the discharge readiness and hip function of hip replacement patients.

Objective:To investigate the correlation between remnant cholesterol/high-density lipoprotein cholesterol ratio (RC/HDL-C) and metabolic dysfunction-associated fatty liver disease (MAFLD) in health check-up population.Methods:It was a cross-sectional study. A total of 5 299 subjects who received physical examination in the Health Management Center of Renmin Hospital of Wuhan University from January to December in 2023 and met the admission criteria were selected as the research subjects. The subjects were examined by demography, anthropometry, laboratory tests and liver instantaneous elastography. The Chi-square test, t-test, one-way analysis of variance, Mann-Whitney U test and Kruskal-Wallis H test were used to compare the indexes between the subjects with and without MAFLD. The subjects were divided into 4 groups (Q1-Q4 groups) according to the RC/HDL-C ratio quartiles by quartile method, and the indexes in each group were compared. The receiver operating characteristic (ROC) curves were drawn using MedCalc software and compared to assess the diagnostic efficacy of the RC/HDL-C ratio for MAFLD. Results:With the increase of RC/HDL-C ratio, the detection rate of MAFLD (12.56% vs 43.48%), male proportion (55.68% vs 85.60%), total cholesterol (TC) [(4.63±0.82) vs (5.10±1.06) mmol/L], triglyceride (TG) [0.90(0.71, 1.15) vs 2.58(1.96, 3.50) mmol/L], alanine aminotransferase (ALT) [17.00(13.00, 24.00) vs 26.00(19.00, 38.00) U/L], aspartate aminotransferase (AST) [20.00(17.00, 24.00) vs 23.00(19.00, 29.00) U/L], and controlled attenuation parameter (CAP) [(239.32±40.52) vs (274.60±44.98) dB/m] increased gradually, while high-density lipoprotein cholesterol (HDL-C) [1.40(1.20, 1.64) vs 0.93(0.84, 1.04) μmol/L] decreased gradually (all P<0.05). ROC curves showed that the AUC value of RC/HDL-C ratio was significantly higher in identifying MAFLD when compared with TC, HDL-C, LDL-C, non-HDL-C and RC (AUC=0.676, P<0.05). Conclusions:The RC/HDL-C ratio is positively correlated with the risk of morbidity of MAFLD in health check-up population.

Inflammatory bowel disease (IBD) is an idiopathic intestinal inflammatory condition with chronic and relapsing manifestations and is characterized by a disturbance in the interplay between the intestinal microbiota, the gut, and the brain. The microbiota-gut-brain axis involves interactions among the nervous system, the neuroendocrine system, the gut microbiota, and the host immune system. Increasing published data indicate that psychological stress exacerbates the severity of IBD due to its negative effects on the microbiota-gut-brain axis, including alterations in the stress response of the hypothalamic-pituitary-adrenal (HPA) axis, the balance between the sympathetic nervous system and vagus nerves, the homeostasis of the intestinal flora and metabolites, and normal intestinal immunity and permeability. Although the current evidence is insufficient, psychotropic agents, psychotherapies, and interventions targeting the microbiota-gut-brain axis show the potential to improve symptoms and quality of life in IBD patients. Therefore, further studies that translate recent findings into therapeutic approaches that improve both physical and psychological well-being are needed.
Humans ; Inflammatory Bowel Diseases/metabolism* ; Stress, Psychological/microbiology* ; Gastrointestinal Microbiome/physiology* ; Brain/metabolism* ; Hypothalamo-Hypophyseal System ; Pituitary-Adrenal System ; Animals