Background Hypertension is one of the chronic diseases with the highest prevalence in China, and a history of hypertension may potentially exacerbate hearing loss. Investigating the association between long-term blood pressure trends and hearing thresholds could contribute to hearing protection efforts for occupationally noise-exposed populations. Objective By investigating hearing thresholds and blood pressure levels among occupationally noise-exposed workers in an urban rail transit enterprise, and conducting a comprehensive analysis of the association between long-term blood pressure changes and hearing thresholds, to provide data references for health management strategies targeting occupationally noise-exposed workers. Methods Workers exposed to occupational noise at a rail transit enterprise were enrolled as study subjects and underwent pure-tone audiometry. Group-based trajectory modeling was employed to identify blood pressure trajectories. Categorical data were compared using chi-square tests, while normally distributed continuous variables were analyzed via t-tests and analysis of variance (ANOVA). Generalized linear mixed models (GLMMs) were subsequently applied toexamine associations between these trajectory groups and high-frequency hearing thresholds. Results Among 2 002 occupationally noise-exposed workers, the median (P₂₅, P₇₅) age was 32 (28, 35) years, with a median (P₂₅, P₇₅) working tenure of 7 (3, 10) years. In 2019, the positive hypertension rate was 9.04%, with a mean systolic blood pressure (SBP) of (122.97±11.60) mmHg and a mean diastolic blood pressure (DBP) of (76.37±9.02) mmHg. The hearing loss prevalence was 10.1%, showing bilateral high-frequency average hearing thresholds of (17.18±8.71) dB and speech-frequency average thresholds of (13.79±3.46) dB. Three distinct trajectory groups were identified for both SBP and DBP. Compared with other trajectory groups, the high-stable DBP group exhibited significantly higher hearing loss prevalence (χ²=6.34, P=0.042) and elevated high-frequency hearing thresholds (all Ps<0.05). Specifically, within the 30-39 age subgroup, the moderate-stable DBP group demonstrated 1.96 dB lower high-frequency thresholds than the high-stable group [β(95%CI): −1.96 (−3.61, −0.32), P=0.020]. Conclusion Among occupationally noise-exposed workers in a municipal rail transit enterprise, DBP trajectories demonstrated a positive association with high-frequency hearing thresholds. Notably, in young and middle-aged occupationally noise-exposed populations, DBP may exert a more critical influence than SBP on the progression of hearing loss.

Hepatitis B virus (HBV) infection represents a significant global health challenge. Current therapeutic options, such as interferon and nucleoside analogues (NAs), are limited by issues including long-term medication toxicity, the virus's propensity to develop drug resistance, and the inability to eradicate covalently closed circular DNA (cccDNA). Core protein allosteric modulators (CpAMs), as an emerging class of anti-HBV drugs, target HBcAg to interfere with capsid assembly. This not only blocks viral nucleocapsid formation and inhibits viral replication but also indirectly destabilizes the cccDNA pool, while exhibiting a relatively high genetic barrier to resistance. This article systematically evaluates HBV drug resistance to CpAMs and proposes anti-resistance strategies, including the combination of nucleoside analogues with CpAMs, enhancing protein-drug interactions, targeting HBcAg degradation, designing multi-target inhibitors, and employing combination therapy. Looking ahead, the integration of structural biology, computational chemistry, and immunotherapy will offer innovative approaches for developing novel, highly effective, and low-resistance inhibitors, thereby advancing the functional cure of hepatitis B.

Objective:To explore the association between thyroid function and chronic kidney disease (CKD) in adults.Methods:A cross-sectional study was conducted in adults who received health checkup in the First Affiliated Hospital of Shandong First Medical University from January to December in 2021. Clinical data were collected, including age, gender, height, weight, blood pressure, etc. And blood glucose, blood lipid, blood creatinine, blood uric acid, routine urine function, thyroid function (free triiodine, free thyroxine, thyroid stimulating hormone) were measured. Multivariate logistic regression model was used to investigate the correlation between thyroid function indicators and the onset of CKD; and receiver operator characteristic (ROC) curve was used to explore the ability of thyroid function indicators in evaluating CKD.Results:In the study, 46 342 adults with an average age of (47.6±14.3) years were enrolled, of which 56.2% were males. The prevalence of DeGFR (eGFR<60 ml·min -1·(1.73 m 2) -1), proteinuria and CKD was 1.15%, 0.53% and 1.58%, respectively. The TSH subgroup analysis showed that the prevalence of DeGFR, albuminuria and CKD in the hypothyroidism group was significantly increased to 1.07%, 2.36% and 3.20%, respectively (all P<0.05). After adjusting for confounding factors, multivariate logistic regression analysis showed that FT3 was negatively associated with CKD ( OR=0.63, 95% CI: 0.54-0.74), however FT4 ( OR=1.05, 95% CI: 1.03-1.07) and TSH ( OR=1.03, 95% CI: 1.01-1.04) were positively correlated with CKD. Similar results were obtained in the subgroup without hypertension and diabetes ( P<0.05). The ROC analysis indicated that FT3 had a better capability for evaluating CKD than FT4 and TSH, with an area under the curve of 0.63, a cut-off value of 4.18 pmol/L, and a sensitivity and specificity of 57.5% and 62.6%, respectively. Conclusions:Thyroid function status is closely associated with the onset of CKD in the adult population receiving health check-up. FT3 is a risk factor for the onset of CKD.

Objective:To investigate the factors contributing to in-hospital mortality among elderly patients aged 80 and above with gastrointestinal bleeding(GIB).Additionally, it seeks to assess the predictive ability of the electronic frailty index(eFI)in determining the risk of in-hospital mortality in GIB patients.Methods:A retrospective analysis was performed among 624 patients aged 80 and above with GIB who were admitted to Beijing Hospital between July 2013 and September 2019.The patients were categorized into two groups based on their discharge outcomes: those who survived and those who did not.The eFI was developed using a cumulative deficit model utilizing data from the hospital's electronic medical records.The study examined the clinical features and risk factors associated with in-hospital mortality among these elderly patients.The effectiveness of eFI in predicting in-hospital mortality in elderly patients with gastrointestinal bleeding was evaluated by calculating the area under the curve(AUC)of the receiver operating characteristic(ROC)curve.Results:Among a total of 624 patients aged between 80 and 102 years, the average age was(83.0±6.4)years, with 339 being male.A majority of the patients, 581 cases(93.1%), had an eFI ≥ 0.15.A comparison between the survival group(380 cases)and the death group(244 cases)revealed that the latter had higher eFI values(0.39±0.09 vs.0.29±0.11, t=-11.452, P<0.001), along with higher rates of heart failure, chronic kidney disease, and malignant tumors, as well as lower body mass index, hemoglobin, albumin, and total cholesterol levels, and higher alanine aminotransferase and D-dimer levels(all P<0.05).Logistic regression analysis indicated that eFI( OR=2.322, 95% CI: 1.840-2.929, P<0.001), malignant tumor( OR=1.833, 95% CI: 1.141-2.860, P<0.001), and albumin<35 g/L( OR=1.826, 95% CI: 1.200-2.777, P<0.001)were independent risk factors for in-hospital death in elderly patients aged 80 and over with gastrointestinal bleeding.With every 0.1 increase in eFI, the risk of in-hospital death rose by 1.322 times.The AUC of eFI for predicting in-hospital mortality was 0.751(95% CI: 0.713-0.789, P<0.001).An eFI of ≥0.33 demonstrated a sensitivity of 77.9% and a specificity of 60.3% in predicting in-hospital mortality in elderly patients aged 80 and over with GIB. Conclusions:The eFI serves as an important independent risk factor for in-hospital mortality among patients aged 80 and above who experience GIB.It can effectively assess the prognosis of elderly individuals facing GIB.

Objective To investigate the difference in visual quality between oval and round corneal flaps in femtosecond excimer laser in situ keratomileusis(FS-LASIK).Methods In a prospective randomized controlled clinical study,patients who voluntarily underwent FS-LASIK surgery in Wuhan University Affiliated Aier Ophthalmology Hospital from June 2022 to February 2023 were randomly divided into oval valve group and round valve group,with 36 patients(72 eyes)in each group.During FS-LASIK,oval and round corneal flaps were made,and excimer laser surgery was performed in parallel.Observe intraoperative and postoperative complications.The unaided visual acuity(UCVA)and spherical equivalent(SE)at 1 day,1 week,1 month and 3 months after surgery were compared between the two groups at 3 months after surgery,and the modulation transfer function(MTF),Strel ratio(SR)and total higher-order aberration at 3 months after surgery were compared between the two groups.Results All patients had successfully completed the surgery without serious complications.There was no significant difference between the oval valve group and the round valve group in UCVA at 1 day,1 week after surgery,1 month after surgery,3 months after surgery.There was no significant difference between the two groups on the postoperative SE at 1 day,1 week after surgery,1 month after surgery,and 3 months after surgery.There was no significant difference in MTF,SR and total higher-order aberration between the two groups at 3 months after surgery.Conclusion Ideal visual acuity can be achieved with either oval or round corneal flap during FS-LASIK,and there is no significant difference in visual quality between the two in the early postoperativeperiod.

Targeted radiation therapy using radionuclides is a favored approach for treating tumors.This procedure involves the delivery of drugs to the lesion site via carriers or interventional methods,followed by the emission of radiation energy that selectively irradiates the lesion tissue.This approach minimizes damage to normal tissue and achieves the desired therapeutic effect.Factors such as the type of therapeutic radionuclide,radiation energy,physical half-life,method of preparation,and toxicity determine their clinical application.In this paper,the characteristics and clinical application of therapeutic radionuclides were reviewed to providing reference for the clinical application of targeted therapeutic radionuclides.

Immune factors play an important role in recurrent spontaneous abortion(RSA),and immune imbalance affects embryo implantation,growth,and development.There is currently no consensus on the etiology and pathogenesis of RSA caused by immune factors.Based on the theory of latent toxic in TCM and combined with the pathological mechanism of the dynamic changes of immune abnormal substances in the body,this article proposed that latent toxic is the key cause of RSA caused by immune factors.Furthermore,it expounded the pathogenic characteristics of latent toxic:combination of heat and blood stasis hidden in the womb,and latent toxic plays a role in embryo formation under qi deficiency conditions.It is established that latent toxin stagnation in the membrane is the pathogenic mechanism.Moreover,this article revealed the variable pathological changes such as the blockage of the inner membrane system and the outer membrane system.Treatment should be based on the basic methods of tonifying qi and nourishing blood,tonifying kidney to secure the Thoroughfare Vessel,clearing heat and cooling blood,promoting blood circulation and removing blood stasis.This article could provide a theoretical basis for TCM syndrome differentiation and treatment of RSA caused by immune factors.

ObjectiveTo explore the possible mechanism of Bushen Huoxue Formula （补肾活血方， BHF） in the treatment of Parkinson's disease （PD） from the the perspective of intestinal flora. MethodsSeventy-two male C57/BL6J mice were randomly divided into blank group， model group， Madopar group and low-， medium- and high-dose BHF groups， with 12 mice in each group. The mice in the blank group were intraperitoneally injected with 10 ml/kg of normal saline， and those in the other groups were intraperitoneally injected with 30 mg/kg of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine （MPTP） at a concentration of 3 mg/ml to induce PD mice model， both once a day for 7 consecutive days. After successful modeling， the low-， medium-， and high-dose BHF groups were given 7.5， 15， and 30 g/（kg·d） of BHF by gavage， respectively， while the Madopar group was given 112.5 mg/（kg ·d） of Domedopar tablets by gavage， and the blank group and the model group were given 15 ml/（kg·d） of distilled water， all once a day for 14 consecutive days. The rod climbing test， rotating rod test， grip strength test and weight-bearing swimming test were used to evaluate the behavioral indicators of mice. Western blotting was used to measure the protein expression levels of Toll-like receptor （TLR）/nuclear factor kappa B （NF-κB） pathway inflammatory factors in the mouse ileum， including Toll-like receptor 2 （TLR2）， Toll-like receptor 4 （TLR4）， NF-κB， tumor necrosis factor α （TNF-α）， interleukin 6 （IL-6）， and interleukin 17 （IL- 17）. 16S rRNA high-throughput sequencing was used to analyze changes in mouse intestinal flora. ResultsCompared to those in the blank group， the mice in the model group had longer bottoming time when climbing the pole， reduced grip strength， shortened rotary pole duration and swimming duration， and increased protein expression levels of TLR2， TLR4， NF-κB， TNF-α， and IL-6 in the ileal tissue （P＜0.01）. Compared to the model group， the Madopar group and the low-， medium- and high-dose BHF groups had shortened bottoming time of the climbing pole and increased grip strength； the Madopar group and the high-dose BHF group had prolonged rotary pole duration， and reduced protein expressions of TLR2， TLR4， NF-κB， TNF-α， IL-6， and IL-17 levels； and only the high-dose BHF group had prolonged swimming duration （P＜0.05 or P＜0.01）. Compared to those in the low-dose BHF group， the bottoming time of the climbing pole were shorter in the moderate- and high-dose groups （P＜0.05 or P＜0.01）， and the grip strength increased while the protein expression levels of TLR2， TLR4 and IL-17 decreased in the high-dose group （P＜0.05 or P＜0.01）. The intestinal flora results showed significant differences between the blank group and the model group in the Dominance index， Pielou_e index， Shannon index， and Simpson index （P＜0.05 or P＜0.01）. Compared to those of the model group， the Shannon index， Chao1 index， and Observed_otus index of the Madopar group， as well as the Chao1 index， Observed_otus index， Dominance index， Pielou_e index， Shannon index， and Simpson index of the high-dose BHF group all showed significantly statistical differences （P＜0.05 or P＜0.01）. At the phylum level， the relative abundance categories of bacterial phyla with statistically significant differences in each group included Proteobacteria， Bacteroidetes， and Firmicutes （P＜0.05 or P＜0.01）. At the genus level， the relative abundance categories of bacterial genera with statistically significant diffe-rences among each group included Muribaculaceae， Akkermansia， and Helicobacter pylori （P＜0.05 or P＜0.01）. ConclusionThe possible mechanism of BHF in treating PD may be to reconstruct the disordered intestinal flora structure and improve the inflammatory response.

Humans ; Diabetic Nephropathies/pathology* ; Kidney/pathology* ; Biopsy ; Diabetes Mellitus, Type 2/pathology* ; Retrospective Studies ; Glomerular Filtration Rate ; Disease Progression

Objective:To study the regulatory effect of miR-200a on mesenchymal-epithelial transition factor (MET) and its impact on the biological behavior of hepatoma carcinoma cells.Method:A luciferase reporter assay was used to determine miR-200a's regulatory impact on MET. Human hepatoma HepG2 cells were divided into a control group, a miR-200a group, a MET overexpression group, and a co-transfection group (miR-200a+MET). After culture, cell proliferation ability, cell migration ability, apoptosis, cell invasion ability, and the expression of MET and apoptosis-related (Bcl-2, Caspase-3, Bax) proteins were detected and observed by cell counting kit-8 (CCK-8), scratch assay, Annexin V-FITC staining, transwell chambers, and western blotting. The two groups were compared using the independent sample t-test. The multiple groups were statistically analyzed using one-way ANOVA.Results:The luciferase experiment showed that miR-200a had target MET. The proliferation rate, number of invasions in cells (55.00 ± 7.21, 85.00 ± 7.94, 164.67 ± 19.22, 104.00± 12.29), scratch healing rate (28.33% ± 5.03%, 61.67% ± 4.04%, 74.67% ± 7.02%, 49.33% ± 9.02%), and expression levels of MET, Bcl-2, and Caspase-3 proteins were lower in the miR-200a group than those in the control group, MET overexpression group, and co-transfection group, while the MET overexpression group had higher indexes than the other three groups, with statistically significant differences between the groups ( P <0.05). The apoptosis rate of HepG2 cells and the expression level of Bax protein were higher in the miR-200a group than those in the control group, MET overexpression group, and co-transfection group (19.25% ± 2.98%, 6.80% ± 1.15%, 3.42% ±0.76%, 9.90% ± 2.72%), while the levels of various indexes in the MIF overexpression group were lower than those in the other three groups. The control group and co-transfection group were between the two groups, and the difference between the groups was statistically significant ( P <0.05). Conclusion:HepG2 cell proliferation, migration, invasion, and cell apoptosis induction can be inhibited by miR-200a, and the functional mechanism for this may be associated with the miR-200a target’s ability to down-regulate MET expression in HepG2 cells.