Unlike chemosynthetic drugs designed for specific molecular and disease targets,active small-molecule natural products typically have a wide range of bioactivities and multiple targets,necessitating extensive screening and development.To address this issue,we propose a strategy for the direct in situ micro-dynamic examination of potential drug candidates to rapidly identify their effects and mechanisms of action.As a proof-of-concept,we investigated the behavior of mussel oligosaccharide(MOS-1)by tracking the subcellular dynamics of fluorescently labeled MOS-1 in cultured cells.We recorded the entire dynamic process of the localization of fluorescein isothiocyanate(FITC)-MOS-1 to the lysosomes and visualized the distribution of the drug within the cell.Remarkably,lysosomes containing FITC-MOS-1 actively recruited lipid droplets,leading to fusion events and increased cellular lipid consumption.These drug behaviors confirmed MOS-1 is a candidate for the treatment of lipid-related diseases.Furthermore,in a high-fat HepG2 cell model and in high-fat diet-fed apolipoprotein E(ApoE)-/-mice,MOS-1 significantly promoted triglyceride degradation,reduced lipid droplet accumulation,lowered serum triglyceride levels,and mitigated liver damage and steatosis.Overall,our work supports the prioritization of in situ visual monitoring of drug location and distribution in subcellular compartments during the drug development phase,as this methodology contributes to the rapid identification of drug indications.Collectively,this methodology is significant for the screening and development of selective small-molecule drugs,and is expected to expedite the identification of candidate molecules with me-dicinal effects.

The treatment of head and neck cancer is dominated by surgery and radiochemotherapy.For elderly patients,however,the rationality of invasive treatment is questioned in clinical practice.Although the proportion of geriatric patients with head and neck canc-er is increasing,there are few consistent standards in the literature and guidelines.From the perspective of evidence-based medicine,this paper presents current evidence for treatment so as to provide specific recommendations for treating head and neck cancer in the elderly.Furthermore,based on a systematic literature review,a clinical algorithm is proposed to evaluate the treatment risk of elderly patients with head and neck cancer.

Objective To study the clinical characteristics and related factors affecting the severity of acute tinnitus in patients.Methods A retrospective analysis was conducted on the data of 319 patients with acute tinni-tus.All patients had detailed case history,including basic patient information,tinnitus location,course of disease,acoustic characteristics of tinnitus,hearing loss,combined headache,dizziness,aural fallness,earache and other symptoms,as well as accompanying clinical diseases.All patients completed the tinnitus handicap inventory(THI),generalized anxiety disorder(GAD-7),patient health questionnaire(PHQ-9),pittsburgh sleep quality index(PSQI),hyperacusis questionnaire(HQ),type D personality scale-14(DS-14),etc.The mild tinnitus group was determined based on a THI score of ≤36.The moderate tinnitus group was determined based on a THI score of 38～56.The severe to extremely severe tinnitus group was determinded based on THI 56～100.THI grouping was used as the dependent variable and the above factors as independent variables.The correlation between each factor and the severity of acute tinnitus was analyzed using ordered multinomial logistic regression.Results Among 319 patients with acute tinnitus,158(49.5％)were in the mild tinnitus group,and 72(22.6％)were in the moderate tinnitus group,and 89(27.9％)were in severe to extremely severe tinnitus group.Ordered multinomial logistic re-gression analysis found that hyperacusis(OR=3.921),anxiety(OR=2.495),depression(OR=2.921),and D-type personality(OR=0.349)were associated with the severity of acute tinnitus(P＜0.05),with more serere tin-nitus in these patients.Conclusion Hyperacusis,anxiety,depression,and D-type personality may be factors that affect the severity of acute tinnitus,so high attention should be paid when treating patients with acute tinnitus.

Objective To observe the value of tissue motion mitral annular displacement(TMAD)technique to assess left ventricular function in patients with cardiac amyloidosis.Methods A total of 34 adult patients with cardiac amyloidosis diagnosed by pathology were retrospectively included as the observation group,and 32 healthy adults were collected as the control group for the same period.Basic data of the subjects were collected,and data of routine ultrasonic parameters of left ventricular function and TMAD parameters were obtained,and then compared between groups.The correlation of TMAD parameters with left ventricular ejection fraction(LVEF)or mitral annular plane systolic excursion(MAPSE)were assessed.Results Compared with the control group,the observation group had higher levels of body surface area(BSA),systolic blood pressure,N-terminal pro-B-type natriuretic peptide(NT-proBNP),creatinine and urea(all P＜0.05).The observation group had increased values of ascending aorta(AO),left atrium(LA),interventricular septum(IVS),left ventricular posterior wall thickness in diastole(LVPWD),pulmonary artery(PA),and early diastolic peark velocity of mitral inflow(peak E),while smaller values of left ventricular end-diastolic dimension(LVEDD),LVEF,fractional shortening(FS),early diastolic tissue Doppler velocity E'septal(IVS E')and lateral(LW E')and MAPSE(all P＜0.05),and the LVEF in observation group was(58.18±7.09)％.For TMAD patameters,the observation group had smaller values of the following parameters on apical four chamber(A4C)view as medial displacement of mitral valve annulus(A4C MV1),displacement of lateral mitral valve annulus(A4C MV2),displacement of the midpoint of the mitral valve annulus(A4C Midpt)and the corresponding percentage(A4C Midpt％),as well as smaller values of the following paramets on apical two chamber(A2C)view as A2C MV1,A2C MV2,A2C Midpt and A2C Midpt％(all P＜0.05).In the observation group,A4C Midpt％showed a moderate positive correlation with LVEF(r=0.488,P＜0.05),and A2C Midpt showed a high positive correlation with M APSE(r=0.712,P＜0.05),and A4C MV2,A4C Midpt,A4C Midpt％,A2C MV1,A2C MV2,A2C Midpt％all showed a moderate positive correlation with MAPSE(r=0.420 to 0.691,all P＜0.05).Conclusion Compared with LVEF,the TMAD parameters might reflect the changes in left ventricular systolic function more sensitively in patients with cardiac amyloidosis.

Objective To construct and validate a risk prediction model for delayed healing of venous leg ulcer(VLU),so as to provide a reference basis for early identification of people at high risk of delayed healing.Methods Using a convenience sampling method,331 VLU patients attending vascular surgery departments in 2 tertiary A hospitals in Sichuan Province from January 2018 to December 2022 were selected as a modeling group and an internal validation group,and 112 patients admitted to another tertiary A hospital were selected as an external validation group.Risk factors for delayed healing in VLU patients were screened using univariate analysis,LASSO regression,and multivariate logistic regression analysis,and a risk prediction model was constructed using R software,and the predictive effects of the models were examined using the area under the receiver operating characteristic curve,the Hosmer-Lemeshow test,decision curve,and the bootstrap resampling for internal validation and spatial external validation were performed,respectively.Results The predictors that ultimately entered the prediction model were diabetes(OR=4.752),deep vein thrombosis(OR=4.104),lipodermatosclerosis(OR=5.405),ulcer recurrence(OR=3.239),and ankle mobility(OR=5.520).The model had good discrimination(AUC:0.819 for internal validation and 0.858 for external validation),calibration(Hosmer-Lemeshow test:χ2=13.517,P=0.095 for internal validation and χ2=3.375,P=0.909 for external validation)and clinical validity.Conclusion The model constructed in this study has good differentiation and calibration,and it can effectively predict people at high risk of delayed healing of VLU,which facilitates targeted clinical interventions to improve ulcer outcomes and reduce the risk of delayed ulcer healing.

OBJECTIVE: To observe the clinical effect and safety of fire needle therapy combined with bladder function training on neurogenic bladder (NB) caused by spinal cord injury. METHODS: A total of 60 patients with NB caused by spinal cord injury were randomly divided into an observation group and a control group , with 30 cases in each group. On the basis of conventional treatment with western medicine, the bladder function training was adopted in the control group, once a day and for 4 weeks. In the observation group, on the basis of the interventions as the control group, fire needling was operated at bilateral Sanyinjiao (SP 6) and Guanyuan (CV 4) and Zhongji (CV 3), once every two days and for 4 weeks (14 interventions in total). Separately, at the baseline and in 2 and 4 weeks of interventions, the urination conditions (average daily urination frequency, average daily leakage frequency, average daily single urination volume) were recorded in the two groups; the urodynamic parameters (maximum flow rate [Qmax], maximum detrusor pressure at maximum flow rate [PdetQmax], residual urine volume [RUA], maximum cystometric capacity [MCC], and bladder pressure) were detected; the neurogenic bladder symptom score (NBSS), urinary symptom distress score (USDS) were observed. Before and after treatment, the score of World Health Organization quality of life assessment scale-brief (WHOQOL-BREF) was observed in the two groups. The therapeutic effect, the incidence of urinary infection, and the safety were evaluated. RESULTS: In 2 and 4 weeks of interventions, the average daily urination frequency, the average daily leakage frequency, RUA, and the scores of NBSS and USDS decreased in the two groups when compared with the baseline (P<0.05). In 4 weeks of interventions, the above-mention outcomes were lower than those in 2 weeks of interventions (P<0.05); and the results in the observation group were lower in 2 and 4 weeks of interventions when compared with the control group (P<0.05). In 2 and 4 weeks of interventions, the average daily single urination volume, Qmax, PdetQmax, MCC, and bladder pressure increased in the two groups compared with the baseline (P<0.05). In 4 weeks of interventions, the above-mention outcomes were elevated in comparison with those in 2 weeks of interventions (P<0.05); and except for bladder pressure, the results in the observation group in 2 and 4 weeks of interventions were higher when compared with the control group (P<0.05). In 4 weeks of interventions, the scores of each dimension and the total scores of WHOQOL-BREF increased in comparison with the baseline in the two groups (P<0.05), and the scores of the observation group were higher than those of the control group (P<0.05). The incidence of urinary infection was 0% (0/30) in the observation group and 10.0% (3/30) in the control group, without significant difference (P>0.05). The total effective rate of the observation group was 93.3% (28/30), which was higher than that (73.3%, 22/30) of the control group (P<0.05). No serious adverse reactions occurred in the patients of the observation group. CONCLUSION Fire needle therapy combined with bladder function training can effectively relieve the clinical symptoms, ameliorate urination, restore bladder function and improve the quality of life in the patients with NB caused by spinal cord injury. This therapeutic regimen presents a high safety in practice.
Humans ; Spinal Cord Injuries/therapy* ; Female ; Male ; Acupuncture Therapy ; Middle Aged ; Adult ; Urinary Bladder, Neurogenic/etiology* ; Urinary Bladder/physiopathology* ; Urination ; Young Adult ; Treatment Outcome ; Aged ; Adolescent ; Combined Modality Therapy

Objective:To compare the clinical value of visual analogue scale （VAS）, Lebel scale and total nasal symptom scores （TNSS） in evaluating nasal allergen provocation test （NAPT）. Methods:A total of 151 patients suspected of allergic rhinitis admitted to the Department of Otolaryngology-Head and Neck Surgery of our hospital from April 2020 to September 2020 were included, of which 76 were positive for house dust mites and 75 were negative for allergens. Nasal airway resistance（NAR） was measured by active anterior nasal manometry. Nasal symptoms were evaluated by VAS, Lebel and TNSS. House dust mite allergen was used for NAPT by spray method. An increase≥40% in NAR was used as the gold standard for objective evaluation of NAPT. ROC curves of VAS, Lebel and TNSS were drawn to compare the evaluation effectiveness of different subjective evaluation methods, and the optimal critical point of each ROC curve was obtained. Results:With NAR increased by ≥40% as the gold standard, the area under ROC curve of VAS was 0.884, and the sensitivity and specificity were 97.75% and 80.65%, respectively. The area under ROC curve of Lebel was 0.773, and the sensitivity and specificity were 68.54% and 75.81%, respectively. The area under ROC curve of TNSS was 0.792, and the sensitivity and specificity were 68.54% and 79.03%, respectively. There was no significant difference between Lebel and TNSS（P>0.05）. The VAS differed significantly from Lebel and TNSS（P<0.05）. The Kappa values of VAS, Lebel, TNSS and NAR were 0.803, 0.432 and 0.459, respectively. Conclusion:The VAS, Lebel, TNSS subjective scale and NAR are consistent in evaluating the efficacy of NAPT, with the VAS assessment showing highest consistency with NAR. As objective assessment instruments are not widely used in China, subjective assessment method could be adopted to evaluate the efficacy of NAPT in clinical practice, and VAS scale is recommended as a priority.
Animals ; Humans ; Allergens ; Nasal Provocation Tests/methods* ; Rhinitis, Allergic/diagnosis* ; Nose ; Pyroglyphidae

Objective:To analyze the genetic and environmental factors that may contribute to the development of allergic rhinitis (AR) in patients, and provide a scientific basis for formulating intervention measures.Methods:This is a case-control study. A cross-sectional survey was conducted on AR patients who received treatment at The First Affiliated Hospital of Nanchang University from June 2017 to March 2019 using a self-designed questionnaire on AR susceptibility factors. Logistic regression analysis of AR susceptibility factors was performed.Results:There were 242 patients in the AR group and 258 patients in the non-AR group (control group). The average age of all patients was (13.16 ± 5.63) years. 56.8% of included patients were male. Multivariate logistic regression analysis showed that AR onset was associated with neonatal jaundice ( OR = 6.043), respiratory infections within 6 months after birth ( OR = 8.123), diarrhea ( OR = 3.868), eczema ( OR = 4.540), living in urban areas ( OR = 2.477), home decoration after birth ( OR = 3.042), moldy ceilings or walls ( OR = 38.255), home gardening ( OR = 3.752), and exposure to smoking environments ( OR = 2.574). Conclusion:The etiology of AR is complex, and its onset is influenced by various factors such as genetic factors, environmental factors, and related disease factors. It is necessary to strengthen the promotion and education of AR prevention knowledge, pay attention to environmental hygiene, and take personal protection measures.

Pulmonary fibrosis(PF)is an irreversible lung disease that is characterized by excessive scar tissue with a poor median survival rate of 2-3 years.The inhibition of transforming growth factor-β receptor type-Ⅰ(TGF-β RI)by an appropriate drug may provide a promising strategy for the treatment of this disease.Polygonum cuspidatum(PC)is a well-known traditional Chinese herbal medicine which has an anti-PF effect.Accordingly,a combination of high resolution mass spectrometry with an in silico strategy was developed as a new method to search for potential chemical ingredients of PC that target the TGF-β RI.Based on this strategy,a total of 24 ingredients were identified.Then,absorption,distribution,meta-bolism,and excretion(ADME)-related properties were subsequently predicted to exclude compounds with potentially undesirable pharmacokinetics behaviour.Molecular docking studies on TGF-β RI were adopted to discover new PF inhibitors.Eventually,a compound that exists in PC known as resveratrol was proven to have excellent biological activity on TGF-β RI,with an ICso of 2.211 μM in vitro.Furthermore,the complex formed through molecular docking was tested via molecular dynamics simulations,which revealed that resveratrol had strong interactions with residues of TGF-β RI.This study revealed that resveratrol has significant potential as a treatment for PF due to its ability to target TGF-β RI.In addition,this research demonstrated the exploration of natural products with excellent biological activities toward specific targets via high resolution mass spectrometry in combination with in silico technology is a promising strategy for the discovery of novel drugs.

Objective:To explore the application effect of a new evaluation system based on virtual simulation system in the evaluation of functional science experiment teaching.Methods:The data of students' learning in the 2019-2020 academic year were collected, and the impact of using virtual simulation teaching system on the achievement of teaching goals under the new teaching evaluation standard was comparatively analyzed. Questionnaire survey was conducted to study students' evaluation on the virtual simulation teaching system. SPSS 22.0 was used for chi-square test.Results:The students who used the new formative evaluation standard had a virtual academic excellence rate of 75.49% (308/408), while the unused students had an excellence rate of only 32.22% (135/419), with significant differences ( P<0.01). The number of virtual simulation items required for different teaching objectives were 4, 11 and 14, respectively, and the corresponding students' virtual simulation system outstanding rate was 99.19% (246/248), 93.14% (380/408), 84.72% (488/576), with significant differences ( P<0.01). And 93.8% (348/371) students thought the learning of the virtual simulation system could help improve the success rate of the experiment, and 93.26% (346/371) of the students believed that it had improved the ability to analyze and deal with unexpected problems in the experimental class. Conclusion:The new evaluation system based on the virtual simulation system can promote the improvement of the experimental teaching quality of functional science.