OBJECTIVE: Recombination events are common and serve as the primary driving force of diverse human adenovirus (HAdV), particularly in children with acute respiratory tract infections (ARIs). Therefore, continual monitoring of these events is essential for effective viral surveillance and control. METHODS: Respiratory specimens were collected from children with ARIs between January 2022 and December 2023. The penton base, hexon, and fiber genes were amplified from HAdV-positive specimens and sequenced to determine the virus type. In cases with inconsistent typing results, genes were cloned into the pGEM-T vector to detect recombination events. Metagenomic next-generation sequencing (mNGS) was performed to characterize the recombinant HAdV genomes. RESULTS: Among 6,771 specimens, 277 (4.09%, 277/6,771) were positvie for HAdV, of which 157 (56.68%, 157/277) were successfully typed, with HAdV-B3 being the dominant type (91.08%, 143/157), and 14 (5.05%, 14/277) exhibited inconsistent typing results, six of which belonged to species B. The penton base genes of these six specimens were classified as HAdV-B7, whereas their hexon and fiber genes were classified as HAdV-B3, resulting in a recombinant genotype designated P7H3F3, which closely resembled HAdV-B114. Additionally, a partial gene encoding L1 52/55 kD was identified, which originated from HAdV-B16. CONCLUSION A novel recombinant, P7H3F3, was identified, containing sequences derived from HAdV-B3 and HAdV-B7, which is similar to HAdV-B114, along with additional sequences from HAdV-B16.
Humans ; Adenoviruses, Human/isolation & purification* ; Respiratory Tract Infections/epidemiology* ; Child, Preschool ; Child ; Recombination, Genetic ; Male ; Beijing/epidemiology* ; Infant ; Female ; Phylogeny ; Adenovirus Infections, Human/epidemiology* ; Acute Disease ; Genome, Viral

Hepatocellular carcinoma （HCC） is a malignant tumor with high incidence and mortality rates worldwide. Recent studies have shown that neutrophil extracellular traps （NETs） play an important role in the development， progression， and immune escape of HCC. NETs are released by neutrophils and mainly consist of DNA， histones， and antimicrobial molecules， and in addition to immune defense， they are also involved in the initiation， metastasis， and thrombosis of HCC. This article elaborates on the formation and regulatory mechanisms of NETs， explores their potential mechanisms in the initiation， metastasis， immune escape， and thrombosis of HCC， and discusses the prospect of NETs as a target for the diagnosis and treatment of HCC， in order to provide new ideas for the precise treatment of HCC in the future and promote the early diagnosis and effective treatment of HCC.

Objective:To investigate the essential determinants that are critical to initiating the assembly of outer membrane proteins by replacing the POTRA domains of the translocator protein FhaC and the insertase protein TtOmp85 of the Omp85 family. Methods:FhaC, TtOmp85 proteins and their recombinant chimeric proteins after replacing the POTRA domain were obtained by overexpression and purification in vitro. An in vitro reconstitution system was used to investigate the effects of the different domains on the transport efficiency of the substrate outer membrane protein FhaB and the membrane insertion efficiency of OmpA. Results:Replacing the POTRA domain of FhaC with that of TtOmp85 led to the loss of the transport function of FhaB. During the membrane insertion process of OmpA, the FhaC mutant containing the POTRA of TtOmp85 protein acquired the ability to assemble OmpA. Conclusion:The compositional differences in the POTRA domain of Omp85 family proteins determine their abilities to recognize their substrate proteins.

Objective:To explore the latent profiles of cognitive function in older adults with mild cognitive impairment(MCI)and to analyze the influencing factors, as well as to develop targeted interventions.Methods:The data for this study were obtained from a cross-sectional study conducted from May to December 2023.Peterson's criteria and the Chinese guidelines for the diagnosis and treatment of dementia and cognitive impairment(V)were employed to screen for MCI among 1, 650 elderly individuals aged 60 and above in a specific community.The Montreal Cognitive Assessment Scale(MoCA)and the Centre for Epidemiological Studies Depression Scale(CES-D)were utilized to assess cognitive ability and depression levels, respectively.Serum vitamin D3 levels were measured using mass spectrometry.Potential profile models of cognitive function in MCI patients were analyzed using Mplus 8.3, and the influencing factors of the latent profiles were identified through multivariate logistic regression.Results:A total of 327 older adults with MCI were initially screened, revealing a prevalence rate of 19.82%.Out of these, 295 patients were ultimately included in the study.The cognitive impairment of these participants was categorized into three profiles: the mild low-cognitive group(49.15%), the mild low-cognitive with severely low-abstraction group(41.70%), and the severely low-cognitive group(9.15%).Logistic regression analysis identified several independent predictors for the severely low-cognitive group among older adults with MCI: education level(primary and below compared to high school and above: OR=7.343, P<0.001; junior high compared to high school and above: OR=1.689, P=0.004), depression level( OR=1.120, P=0.002), and napping habits(with napping habits compared to without: OR=0.255, P=0.006).Additionally, education level( OR=3.535, P<0.001), depression level( OR=1.125, P<0.001), and serum vitamin D3 levels( OR=0.811, P=0.035)were found to be independent predictors for the mild low-cognitive with severely low-abstraction group in older adults with MCI. Conclusions:Cognitive impairment in older adults with MCI exhibits heterogeneity, which can be categorized into three potential profiles.Targeted interventions should be implemented based on the characteristics and influencing factors of each category to mitigate cognitive decline among older adults with MCI.

Objective:To investigate the association between triglyceride glucose index (TyG) and early vascular aging measured by brachial ankle pulse wave velocity (baPWV) in young and middle-aged population.Methods:It was a cross-sectional study. A total of 5 680 subjects aged 20 to 59 years who underwent health check-ups at the Health Management Center of General Hospital of Tianjin Medical University from January to December in 2020 were selected as the research subjects. All the research subjects completed the health risk assessment questionnaire, physical examination, laboratory test, and multi-functional vascular lesion detection. The TyG was calculated and the research subjects were divided into four groups with the quartiles of TyG (Q 1 to Q 4, with a cut-off value of 8.22, 8.60 and 9.01, respectively). The baPWV value was converted into a Z-score, and those with a Z-score above the 95th percentile were defined as having early vascular aging. The Spearman correlation method, multiple linear regression model, binary logistic regression model and the area under the receiver operating characteristic curve (AUC) were used to analyze the association between TyG and early vascular aging. Results:Among the 5 680 middle-aged and young people included in the analysis, there were 3 117 males and 2 563 females, with an age of 46 (39, 52) years, a TyG of 8.60 (8.22, 9.01), and a baPWV of 1 279.25 (1 147.50, 1 434.25) cm/s. The prevalence rate of early vascular aging was 5.02% (285/5 680). Taking group Q 1 as the reference, in the multiple linear regression model adjusted for multiple factors, group Q 4 was significantly associated with a 47.64 (95% CI: 28.18-67.11) cm/s increase in baPWV ( P for trend<0.001). In the multivariate adjusted binary logistic regression model, compared with that in the Q 1 group, the OR of early vascular aging occurrence in the Q 2, Q 3, and Q 4 groups was 1.52 (95% CI: 0.75-3.07), 1.78 (95% CI: 0.89-3.58), and 3.04 (95% CI: 1.47-6.31), respectively. Elevated TyG level was positively correlated with the occurrence of early vascular aging ( P for trend<0.001). The AUC of TyG in predicting early vascular aging was 0.732 (95% CI: 0.704-0.759), with the optimal cut-off value being 8.86. The AUC of TyG in predicting early vascular aging in males was lower than that in females [0.665 (95% CI: 0.628-0.702) vs 0.796 (95% CI: 0.748-0.843)] ( P<0.001). Conclusions:There is a correlation between TyG and early vascular aging measured by baPWV in the middle-aged and young population. When TyG≥8.86, clinical intervention measures should be taken in a timely manner.

Objective:To investigate the drug resistance of newly diagnosed HIV-1 infected patients in Shanghai and to provide reference value for clinical antiretroviral therapy (ART).Methods:The peripheral venous blood plasma of 196 newly diagnosed HIV-1 infected patients screened according to the inclusion and exclusion criteria at the Shanghai Public Health Clinical Center from April to June 2023 was collected, HIV-1 RNA was extracted, the pol region was amplified by reverse transcription-polymerase chain reaction (RT-PCR) for sequencing, the mutation sites and ART drug resistance were analyzed.Results:The plasma of 196 newly diagnosed HIV-1 infected patients was amplified successfully in 162 cases (amplification success rate was 82.65%). The subtypes consisted of CRF07_BC(51.23%), CRF01_AE (27.78%), and others (6.79%), CRF55_01B (5.56%), B (3.70%), CRF01_AE/B (3.70%) and CRF08_BC (1.23%). The overall transmitted drug resistance rate was 7.41%, the protease inhibitors (PIs), non-nucleoside/nucleotide reverse transcriptase inhibitors (NNRTIs), nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs), integrase inhibitors (INSTIs) resistance rates were 3.09%, 3.70%, 0.00% and 0.62%, respectively. The proportion of NNRTIs-related mutation sites in B (66.67%) and CRF55_01B (88.89%) was higher than that in CRF07_BC (13.25%); the proportion of NNRTIs-related mutation sites in CRF55_01B (88.89%) was higher than that in CRF01_AE (22.22%) and other subtypes (18.18%), the difference was statistically significant (all P<0.05). Multivariate logistic regression analysis showed that the probability of PIs-related mutation sites in CRF01_AE/B was 21.71 times that of CRF07_BC[odds ratio ( OR)=21.71, 95% confidence interval ( CI): 3.36-140.27, P=0.001]. Conclusions:The transmitted drug resistance among newly diagnosed HIV-1 infected patients in Shanghai is at the moderate epidemic level, mainly NNRTIs and PIs-related drug resistance, and the INSTIs resistance rate is low, the use of INSTIs in ART regimens should be considered.

OBJECTIVE: To evaluate the clinical efficacy and safety of Yangxue Qingnao Pills (YXQNP) combined with amlodipine in treating patients with grade 1 hypertension. METHODS: This is a multicenter, randomized, double-blind, and placebo-controlled study. Adult patients with grade 1 hypertension of blood deficiency and Gan (Liver)-yang hyperactivity syndrome were randomly divided into the treatment or the control groups at a 1:1 ratio. The treatment group received YXQNP and amlodipine besylate, while the control group received YXQNP's placebo and amlodipine besylate. The treatment duration lasted for 180 days. Outcomes assessed included changes in blood pressure, Chinese medicine (CM) syndrome scores, symptoms and target organ functions before and after treatment in both groups. Additionally, adverse events, such as nausea, vomiting, rash, itching, and diarrhea, were recorded in both groups. RESULTS: A total of 662 subjects were enrolled, of whom 608 (91.8%) completed the trial (306 in the treatment and 302 in the control groups). After 180 days of treatment, the standard deviations and coefficients of variation of systolic and diastolic blood pressure levels were lower in the treatment group compared with the control group. The improvement rates of dizziness, headache, insomnia, and waist soreness were significantly higher in the treatment group compared with the control group (P<0.05). After 30 days of treatment, the overall therapeutic effects on CM clinical syndromes were significantly increased in the treatment group as compared with the control group (P<0.05). After 180 days of treatment, brachial-ankle pulse wave velocity, ankle brachial index and albumin-to-creatinine ratio were improved in both groups, with no statistically significant differences (P>0.05). No serious treatment-related adverse events occurred during the study period. CONCLUSIONS Combination therapy of YXQNP with amlodipine significantly improved symptoms such as dizziness and headache, reduced blood pressure variability, and showed a trend toward lowering urinary microalbumin in hypertensive patients. These findings suggest that this regimen has good clinical efficacy and safety. (Registration No. ChiCTR1900022470).
Humans ; Amlodipine/adverse effects* ; Drugs, Chinese Herbal/adverse effects* ; Male ; Female ; Hypertension/complications* ; Middle Aged ; Treatment Outcome ; Drug Therapy, Combination ; Adult ; Blood Pressure/drug effects* ; Double-Blind Method ; Aged ; Antihypertensive Agents/adverse effects*

Objective:To explore the genetic and clinical characteristics of Guizhou patients with enlarged vestibular aqueduct（EVA） syndrome through combined SLC26A4 variant analysis and clinical phenotype analysis. Methods:Seventy-two EVA patients underwent comprehensive genetic testing using a multiplex PCR-based deafness gene panel and next-generation sequencing（NGS）. The audiological and temporal bone imaging characteristics were compared across mutation subtypes. Results:A total of 27 pathogenic loci of SLC26A4 were detected in 72 patients, including c.919-2A>G in 79.2%（57/72）. A novel deletion（c.1703_1707+6del） was discovered. Among 65 cases, truncated mutations were 89.2%（58/65）, 52.3%（34/65）, 28（43.1%） and 7（10.8%）. No significant differences were observed in the midpoint diameter of the vestibular aqueduct and the incidence of incomplete partitioning typeⅡ（IP-Ⅱ） of the cochlea among the three groups of patients. Moreover, there was no difference in the midpoint diameter of different vestibular pipes or the combination with IP-Ⅱ. Conclusion:The most common mutation site of SLC26A4 in EVA patients in Guizhou is c.919-2A>G, though genotype-phenotype correlations remain elusive. The detection of 27 mutation sites and the discovery of new mutation sites suggested the precise diagnostic significance of NGS technology in EVA patients in Guizhou.
Humans ; Sulfate Transporters ; Vestibular Aqueduct/abnormalities* ; Mutation ; Membrane Transport Proteins/genetics* ; Hearing Loss, Sensorineural/genetics* ; Male ; Female ; Child ; Adolescent ; Child, Preschool ; Adult ; Young Adult ; Phenotype ; High-Throughput Nucleotide Sequencing

Acute pancreatitis (AP) is a life-threatening gastrointestinal disorder for which no effective pharmacological treatments are currently available. One of the pharmacological targets that merits further research is the neurokinin 1 receptor (NK1R), which is found on pancreatic acinar cells and responds to the neuropeptide substance P (SP) that participates in AP. Although a few studies have stated the involvement of SP/NK1R in neurogenic inflammation in AP development, the regulatory mechanism remains unclear. In this study, we found that following activation of NK1R by SP, β-arrestin1, a scaffold protein of NK1R, down-regulated transcription of Adss, Adsl, and Ampd in the purine nucleotide cycle, thereby inhibiting mitochondrial function through fumarate depletion. Interestingly, we identified magnolol as a new and natural NK1R inhibitor with a non-nitrogenous biphenyl core structure. It exhibited a beneficial effect on AP by restoring purine nucleotide cycle metabolic enzymes and fumarate levels. Our study not only provides new therapeutic strategies, leading compounds, and drug translation possibilities for AP, but also provides important clues for the study of downstream mechanisms driven by SP in other diseases.

Tongue squamous cell carcinoma (TSCC) is a prevalent malignancy that afflicts the head and neck area and presents a high incidence of metastasis and invasion. Accurate diagnosis and effective treatment are essential for enhancing the quality of life and the survival rates of TSCC patients. The current treatment modalities for TSCC frequently suffer from a lack of specificity and efficacy. Nanoparticles with diagnostic and photothermal therapeutic properties may offer a new approach for the targeted therapy of TSCC. However, inadequate accumulation of photosensitizers at the tumor site diminishes the efficacy of photothermal therapy (PTT). This study modified gold nanodots (AuNDs) with the TSCC-targeting peptide HN-1 to improve the selectivity and therapeutic effects of PTT. The Au-HN-1 nanosystem effectively targeted the TSCC cells and was rapidly delivered to the tumor tissues compared to the AuNDs. The enhanced accumulation of photosensitizing agents at tumor sites achieved significant PTT effects in a mouse model of TSCC. Moreover, owing to its stable long-term fluorescence and high X-ray attenuation coefficient, the Au-HN-1 nanosystem can be used for fluorescence and computed tomography imaging of TSCC, rendering it useful for early tumor detection and accurate delineation of surgical margins. In conclusion, Au-HN-1 represents a promising nanomedicine for imaging-based diagnosis and targeted PTT of TSCC.
Tongue Neoplasms/diagnostic imaging* ; Carcinoma, Squamous Cell/diagnostic imaging* ; Animals ; Gold/chemistry* ; Mice ; Photothermal Therapy/methods* ; Tomography, X-Ray Computed ; Photosensitizing Agents ; Metal Nanoparticles ; Humans ; Cell Line, Tumor