ObjectiveTo investigate the association of serum exosomal microRNAs （miRNAs） with hepatic inflammatory injury and histological outcomes in patients with chronic hepatitis B （CHB）. MethodsPeripheral serum samples were collected from six healthy adults and six patients with CHB， and size exclusion chromatography was used to extract exosomes. Small RNA sequencing and transcriptomic analysis were used to identify the serum exosomal miRNAs associated with liver inflammatory injury and fibrosis， and quantitative real-time PCR was used for validation in a mouse model of acute liver injury induced by lipopolysaccharide/D-galactosamine， a rat model of liver fibrosis induced by carbon tetrachloride， and 84 CHB patients undergoing liver biopsy twice before and after treatment. The independent-samples t test was used for comparison of normally distributed continuous data between two groups； an analysis of variance was used for comparison between multiple groups， and the Tukey test was used for further comparison between two groups. The Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups； the Kruskal-Wallis H test was used for comparison between multiple groups， and the Dunn test was used for further comparison between two groups. The chi-square test or the Fisher’s exact test was used for comparison of categorical data between groups. The univariate and multivariate Logistic regression analyses were used to investigate influencing factors. ResultsAbnormal expression of serum exosomal miR-122-5p was observed in patients with CHB， and it was downregulated in patients with confluent necrosis and advanced fibrosis. In the mouse model of acute liver injury and the rat model of liver fibrosis， compared with the control group， the model group had a significant reduction in the expression level of miR-122-5p in the liver （P=0.048 and 0.014）， and compared with the patients with mild liver injury， the patients with severe confluent necrosis and advanced fibrosis showed a significant reduction in the expression level of miR-122-5p in liver tissue （P<0.05）. Among the 84 CHB patients， the patients with severe hepatic confluent necrosis or advanced liver fibrosis had a significantly lower expression level of serum exosomal miR-122-5p than those with mild liver injury （P<0.001 and P=0.003）. The multivariate Logistic regression analysis showed that the expression level of miR-122-5p was an independent influencing factor for confluent necrosis （odds ratio ［OR］=0.001， 95% confidence interval ［CI］： 0.000‍ ‍—‍ ‍0.037， P=0.005） and liver fibrosis degree （OR=0.568， 95%CI： 0.331‍ ‍—‍ ‍0.856， P=0.019）. In addition， compared with the patients with low expression of miR-122-5p， the patients with high expression of miR-122-5p before treatment had a significantly higher reversal rate of liver fibrosis after 72 weeks of antiviral therapy （64.3% vs 38.1%， P=0.029）. ConclusionSerum exosomal miR-122-5p in CHB patients is closely associated with the progression of hepatic confluent necrosis and fibrosis， and the reduction in the expression level of miR-122-5p may aggravate hepatic confluent necrosis， promote the progression of fibrosis， and affect the histological outcome of CHB patients after antiviral therapy.

Interferon regulatory factor 4 (IRF4) is a critical transcription factor that governs the differentiation of cluster of differentiation 4⁺ (CD4⁺) T cells. The pathogenesis and progression of psoriasis are primarily attributed to an immune imbalance stemming from the overproduction of interleukin-17A (IL-17A) by T lymphocytes. However, the role of IRF4 in psoriasis remains unexplored. In this study, we found that IRF4 activity is increased in the cutaneous lesions of patients with psoriasis in response to stimulation by IL-23A and IL-1β. This IRF4 elevation heightens its binding to the E1A binding protein p300 (EP300) promoter, triggering the transcription of downstream retinoic acid receptor-related orphan receptor-γt (RORγt) and increasing the secretion of IL-17A, thereby establishing the IL-1β/IL-23A-IRF4-EP300-RORC-IL-17A inflammatory cascade in psoriasis. The alleviation of imiquimod (IMQ)-induced psoriatic-like symptoms was achieved through the creation of a Irf4 ^-/- gene deletion mouse model and pharmacological inhibition using antisense oligonucleotides targeted for Irf4. This amelioration was accompanied by a decreased number of IL-17A-producing CD4⁺ T cells in the skin. The findings of this study suggest that IRF4 plays a crucial role in the promotion of inflammation and exacerbation of IMQ-induced psoriasiform dermatitis. Consequently, IRF4 targeting could be a promising therapeutic strategy.

Objective:To analyze the efficacy of anterior cervical Hybrid surgery and posterior cervical expansive open-door laminoplasty(EODL)in the treatment of multilevel cervical spondylotic myelopathy,and to discuss the selection of surgical methods for the patients with multilevel cervical spondylotic myelopathy.Methods:The retrospective analysis was conducted of 70 patients with multilevel cervical spondylotic myelopathy who underwent surgery at Affilated Beijing Traditional Chinese Medicine Hospital of Capital Medical University from July 2017 to July 2020.Based on the different surgical methods,the patients were divided into anterior group(n=35)and posterior group(n=35).The patients in anterior group underwent Hybrid surgery[anterior cervical discectomy and fusion(ACDF)combined with artificial cervical disc replacement(ACDR)],and the patients in posterior group underwent EODL.The hospitalization time,operation time,intraoperative blood loss,and postoperative drainage volume of the patients in two groups were recorded;the efficacy was evaluated by Japanese orthopaedic association(JOA)score,JOA improvement rate,neck disability index(NDI),visual analogue scale(VAS)for pain,and postoperative satisfaction score;the complications of the patients in two groups after surgery were recorded.Results:Compared with posterior group,the intraoperative blood loss,postoperative drainage volume,hospitalization time,and operation time of the patients in anterior group were significantly decreased(P<0.01),and the preoperative score had no significant difference(P>0.05).At the final follow-up after surgery,compared with posterior group,the JOA score and JOA improvement rate of the patients in anterior group were significantly increased(P<0.01),and the NDI score and VAS score were significantly decreased(P<0.01).Compared with before surgery,the JOA scores of the patients in two groups at the final follow-up after surgery were increased(P<0.01),and the NDI and VAS scores were significant decreased(P<0.01).The postoperative satisfaction of the patients in two groups was high based on the postoperative satisfaction score.There was no significant difference in the incidence of postoperative complication of the patients between two groups(P>0.05).Conclusion:Both the anterior cervical Hybrid surgery and EODL achieve the satisfactory results in the treatment of multilevel cervical spondylotic myelopathy.Hybrid surgery has the advantages of less bleeding and shorter surgery time,and the most suitable surgical method should be chosen clinically based on the actual situation of the patients.

Objective:To explore the effectiveness of 18F-deuterated-Florbetapir (D3FSP) PET/CT imaging in detecting β-amyloid (Aβ) deposition in the brain and its correlation with plasma biomarkers. Methods:A retrospective analysis was conducted on 79 patients (32 males, 47 females; age(66±7)years) who underwent 18F-D3FSP PET/CT imaging from June 2022 to November 2023 at the First Affiliated Hospital, Guangzhou Medical University, as a part of the Greater Bay Area Healthy Aging Brain Longitudinal Cohort Study (GHABS). Based on the Alzheimer′s Disease Neuroimaging Initiative cohort standard protocol, patients were categorized into cognitively unimpaired (CU) group, mild cognitive impairment (MCI) group, and Alzheimer′s disease (AD) group. Brain regions were segmented using the AW workstation and the SUV ratio (SUVR) was calculated with the cerebellum as the reference region. One-way analysis of variance, Bonferroni correction and Pearson correlation analysis were used to analyze data. The ROC curve analysis was used to analyze the cut-off value and the diagnostic efficacy of SUVR. Results:There were 48, 15 and 16 cases in CU, MCI and AD groups respectively. During the transition from CU to MCI and then to AD, there was a rising trend in SUVR ( F values: 11.15-22.38, all P<0.001) across the whole brain and various brain regions (bilateral frontal lobes, bilateral anterior cingulate gyrus, bilateral precuneus, bilateral parietal lobes, bilateral lateral temporal lobes, and bilateral occipital lobes). SUVRs of the right anterior cingulate gyrus and bilateral precuneus were different between the CU and MCI groups (all P<0.017), and those of bilateral frontal lobes, right precuneus, bilateral parietal lobes, bilateral lateral temporal lobes, and bilateral occipital lobes were different between the MCI and AD groups (all P<0.017). SUVRs of brain regions were negatively correlated with cognitive scale scores ( r values: from -0.57 to -0.37, all P<0.001), and were positively correlated with plasma phosphorylated tau181 (p-tau181, r values: 0.50-0.61, all P<0.001). The ROC curve analysis suggested that the cut-off value of SUVR in the precuneus for distinguishing CU from AD was 1.20, with the AUC, sensitivity, specificity and accuracy of 0.85, 12/16, 91.7%(44/48)and 87.5%(56/64), respectively. Conclusion:18F-D3FSP PET/CT imaging has good clinical application value in assessing the deposition sites and the extent of Aβ in the brain, which is related to clinical cognition and plasma p-tau181 level.

Protein S-palmitoylation is a reversible post-translational modification of lipids that regulates protein localization, stability and protein-protein interactions. The thioesterification of palmitate to internal cysteine residues is catalyzed by palmitoyltransferase, while the removal of palmitate is mainly catalyzed by acyl-protein thioesterase. The S-palmitoylation of some tumor-related proteins is abnormally altered in tumor, which is closely related to the biological processes such as tumor cell proliferation, invasion, metastasis, drug resistance and immune response. Furtherly, exploring the characteristics of protein S-palmitoy-lation and its role in tumor progression could deliver new ideas in targeting protein S-palmitoylation for tumor therapy.

With the aging of population, the elderly (≥65 years old) cancer patients have become one of the main populations for cancer care. For inoperable locally advanced head and neck squamous carcinomas, cisplatin-based concurrent chemoradiotherapy is the first-line choice. Several large clinical studies have shown that patients under 70 years of age can still benefit from concurrent chemoradiotherapy, while it should be cautious to apply chemotherapy to patients aged 70-80 years. For elderly patients who are intolerant to cisplatin, carboplatin or other regimens with less gastrointestinal and renal toxicity should be considered. Although anti-epidermal growth factor receptor (EGFR) monoclonal antibodies combined with radiotherapy has been proved to be more effective than radiotherapy alone in total patient population, age-subgroup analysis showed limited benefit in elderly patients. The safety of immune checkpoint inhibitors in elderly patients has been validated and those with high programmed death ligand-1 (PD-L1) expression may benefit from concurrent or neoadjuvant immunotherapy, however, high-level evidence is still lacking. For patients older than 80 years, radiotherapy alone may be superior to concurrent chemoradiotherapy, and hypofractionated radiotherapy for palliative purposes can be safely used in this population.

Background Dentists are a high-risk population of work-related musculoskeletal disorders (WMSDs), where the body part with the highest prevalence is the neck. Objective To analyze potential influencing factors of neck pain among dentists, and explore a prediction model of neck pain in dentists. Methods Dentists from different hospitals in Fuzhou were selected as study subjects by stratified cluster sampling according to hospital characteristics (dental hospitals, general hospitals, and dental clinics). The basic information, presentation of WMSDs, and its influencing factors were investigated by using the Chinese version of Musculoskeletal Disorders Questionnaire and the Subjective Workload Assessment Technique. A total of 655 questionnaires were collected, of which 603 were valid, with an effective rate of 92.1%. Multiple logistic regression was used to analyze potential influencing factors of neck pain in dentists. A prediction model of neck pain of dentists was constructed by using neural network model, and the prediction efficiency of the model was evaluated. Results The neck was the body part with the highest prevalence (43.8%, 264/603) of WMSDs among dentists. The results of multiple logistic regression analysis showed that female (OR=2.709, 95%CI: 1.852-3.962, P <0.001), working age of 10-<20 years (versus <10 years, OR=3.836, 95%CI: 2.471-5.957, P<0.001), keeping head up or down for a long time (OR=8.492, 95%CI: 2.203-32.731, P=0.002), holding head sideways for a long time (OR=2.210, 95%CI: 1.376-3.550, P<0.001), maintaining the same sitting spot for a long time (OR=4.336, 95%CI: 2.192-8.579, P<0.001), and psychological load value ≥70 (versus <40, OR=1.901, 95%CI: 1.038-3.480, P=0.037) increased the risk of neck pain in dentists. Sufficient operating space (OR=0.507, 95%CI: 0.302-0.850, P=0.010) and doing some exercise during work break (OR=0.670, 95%CI: 0.453-0.991, P=0.045) reduced the risk of reporting neck pain among dentists. A neural network prediction model of dentists' neck pain was constructed with 1 hidden layer and 6 hidden layer neurons. The percentage of correct prediction of training set was 89.6%, and the percentage of correct prediction of test set was 83.9%. The order of importance of the independent variables included in the model were working age, holding head sideways for a long time, psychological load, etc. The result of neural network model of neck pain among dentists showed that the area under the curve of receiver operator characteristic (ROC) was 0.940 (95%CI: 0.922-0.958, P<0.001). When the maximum diagnostic value was determined by the ROC curve, the sensitivity was 84.8%, the specificity was 91.2%, and the Youden Index was 0.760. Conclusion Neck pain of dentists is affected by many factors, such as individual factors (gender and working age), ergonomic factors (keeping various postures and operations for a long time, operating space, etc.), psychological factors (different levels of psychological load) and so on. The neural network model can be used as a prediction tool to explore the risk of reporting neck pain among dentists.

Radiotherapy is an essential part of comprehensive treatment, as well as a radical treatment for head and neck cancer (HNC). The COVID-19 has continued so far, imposing a great impact on cancer care. Since conventional fractionated radiotherapy (CFRT, 2 Gy/F) requires as long as more than six weeks of treatment time, a huge challenge for epidemic control is created for both hospitals and patients. Hypofractionated radiotherapy (Hypo-RT) may be more suitable than CFRT for patients during pandemic by increasing the fraction size, thus reducing fraction number and treatment duration. Early studies have explored the application of Hypo-RT in HNC in palliative setting, which partially proved its safety and effectiveness. Recently, the efforts have been made in definitive treatment using hypofractionated regimen, as well as its combination with systemic treatment and immunotherapy. Indeed, regarding the pandemic of COVID-19, Hypo-RT has been recommended by several expert consensus in the HNC. In this review, relevant research progress was summarized and clinical implication of Hypo-RT in COVID-19 pandemic era was discussed.

Calcium oxalate (CaOx) stone is the main type, and its formation is closely related to the metabolism of oxalic acid and calcium. Gut Microbiome is normal microflora which settled in the human intestinal tract and plays an important role in regulating a variety of metabolism in the body. In the past, Oxalobacter formigenes in gut was a protective factor for the formation of CaOx stones. Recently, it has been found that the bacteria regulating oxalate metabolism were not limited to Oxalobacter formigenes. Gut Microbiome of CaOx stones formers is different from healthy people. It regulates the metabolism of oxalic acid in the body through the gut-kidney axis and affect the formation of CaOx stone. The purpose of this study is to describe the characteristics of intestinal flora in patients with CaOx stones, and to summarize its potential function in the formation of CaOx stones and its possible clinical application in the future.

Scutellaria baicalensis (S. baicalensis) and Scutellaria barbata (S. barbata) are common medicinal plants of the Lamiaceae family. Both produce specific flavonoid compounds, including baicalein, scutellarein, norwogonin, and wogonin, as well as their glycosides, which exhibit antioxidant and antitumor activities. Here, we report chromosome-level genome assemblies of S. baicalensis and S. barbata with quantitative chromosomal variation (2n = 18 and 2n = 26, respectively). The divergence of S. baicalensis and S. barbata occurred far earlier than previously reported, and a whole-genome duplication (WGD) event was identified. The insertion of long terminal repeat elements after speciation might be responsible for the observed chromosomal expansion and rearrangement. Comparative genome analysis of the congeneric species revealed the species-specific evolution of chrysin and apigenin biosynthetic genes, such as the S. baicalensis-specific tandem duplication of genes encoding phenylalanine ammonia lyase and chalcone synthase, and the S. barbata-specific duplication of genes encoding 4-CoA ligase. In addition, the paralogous duplication, colinearity, and expression diversity of CYP82D subfamily members revealed the functional divergence of genes encoding flavone hydroxylase between S. baicalensis and S. barbata. Analyzing these Scutellaria genomes reveals the common and species-specific evolution of flavone biosynthetic genes. Thus, these findings would facilitate the development of molecular breeding and studies of biosynthesis and regulation of bioactive compounds.
Evolution, Molecular ; Flavonoids/biosynthesis* ; Genome, Plant ; Plant Extracts/genetics* ; Scutellaria/metabolism* ; Whole Genome Sequencing