OBJECTIVE: To explore the role of the natural compound hesperidin in glycolysis, the key ratelimiting enzyme, in colorectal cancer (CRC) cell lines. METHODS: In vitro, HCT116 and SW620 were treated with different doses of hesperidin (0-500 µmol/L), cell counting kit-8 and colone formation assays were utilized to detected inhibition effect of hesperidin on CRC cell lines. Transwell and wound healing assays were performed to detect the ability of hesperidin (0, 25, 50 and 75 µmol/L) to migrate CRC cells. To confirm the apoptotic-inducing effect of hesperidin, apoptosis and cycle assays were employed. Western blot, glucose uptake, and lactate production determination measurements were applied to determine inhibitory effects of hesperidin (0, 25 and 50 µmol/L) on glycolysis. In vivo, according to the random number table method, nude mice with successful tumor loading were randomly divided into vehicle, low-dose hesperidin (20 mg/kg) and high-dose hesperidin (60 mg/kg) groups, with 6 mice in each group. The body weights and tumor volumes of mice were recorded during 4-week treatment. The expression of key glycolysis rate-limiting enzymes was determined using Western blot, and glucose uptake and lactate production were assessed. Finally, protein interactions were probed with DirectDIA Quantitative Proteomics, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. RESULTS: Hesperidin could inhibit CRC cell line growth (P<0.05 or P<0.01). Moreover, hesperidin presented an inhibitory effect on the migrating abilities of CRC cells. Hesperidin also promoted apoptosis and cell cycle alterations (P<0.05). The immunoblotting results manifested that hesperidin decreased the levels of hexokinase 2, glucose transporter protein 1 (GLUT1), GLUT3, L-lactate dehydrogenase A, 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 2 (PFKFB2), PFKFB3, and pyruvate kinase isozymes M2 (P<0.01). It remarkably suppressed tumor xenograft growth in nude mice. GO and KEGG analyses showed that hesperidin treatment altered metabolic function. CONCLUSION Hesperidin inhibits glycolysis and is a potential therapeutic choice for CRC treatment.
Hesperidin/therapeutic use* ; Colorectal Neoplasms/metabolism* ; Glycolysis/drug effects* ; Animals ; Humans ; Apoptosis/drug effects* ; Mice, Nude ; Cell Movement/drug effects* ; Cell Line, Tumor ; Cell Proliferation/drug effects* ; Glucose/metabolism* ; Cell Cycle/drug effects* ; Mice, Inbred BALB C ; Mice ; HCT116 Cells ; Lactic Acid

Objective·To develope an auditory brainstem implant(ABI)vocoder based on cochlear implant(CI)vocoder characteristics and ABI electrode array topology,and to verify its reliability.Methods·An"n-of-m"coding strategy CI/ABI vocoder was constructed based on MATLAB.Within each frame,only the envelopes of the n channels with the highest energy were selected.The interaction coefficient(IC)(range:1?3),channel numbers(range:5?22),and electrode array topology(CI/ABI)were adjustable parameters,allowing for the synthesis of simulated speech.Psychoacoustic evaluation was employed,recruiting normal hearing subjects to perform closed-set simulated phoneme perception.The phoneme recognition accuracy(20 vowel questions/condition,11 consonant questions/condition)was compared with the corresponding conditions of CI and ABI from reference literature to determine the IC value of the vocoder and verify its reliability.Results·The vocoder successfully synthesized all test stimuli.In the closed-set CI-simulated speech recognition,the simulated vowel and consonant recognition accuracy for IC2 and IC3 conditions showed no significant difference compared to the accuracy reported in the CI reference literature(P＞0.05).The difference in vowel and consonant accuracy between IC2 and the literature was smaller than that between IC3 and the literature(vowel|d|=1.6%vs.20%,consonant|d|=8.4%vs.9.9%),thus determining the optimal interaction coefficient of this model as 2.Subsequently,when modifying the electrode array topology to ABI,it was found that the simulated phoneme recognition accuracy for a 16-channel ABI was significantly lower than that for the 16-channel CI group,consistent with the reported literature.The simulated vowel and consonant accuracy within the 5?8 channel range for ABI showed no significant difference(P＞0.05),also aligning with the trend reported in the literature.Conclusion·A CI/ABI vocoder based on"n-of-m"coding strategy is established and the optimal IC is determined.The established ABI encoder has been evaluated for high reliability through psychoacoustic experiments.It provides suitable technical means for validating ABI-specific coding strategies.

Objective:To utilize routinely available clinical parameters to uncover the clinical features of different clusters in patients with chronic rhinosinusitis with nasal polyp (CRSwNP) through unsupervised clustering analysis.Methods:The clinical data from 155 CRSwNP patients undergoing nasal endoscopic surgery at Renmin Hospital of Wuhan University from 2021 to 2023 were prospectively collected, including 112 males and 43 females, aged from 7 to 87 years. Unsupervised clustering analysis was conducted using various clinical parameters, including age, gender, smoking and drinking history, local eosinophil (EOS) and neutrophil (NEU) counts, comorbid allergic rhinitis (AR), comorbid asthma, recurrence status, serum-specific IgE, total IgE, cytokine levels, peripheral blood EOS count and percentage, Lund-Mackay CT score, the ratio of CT scores for the maxillary sinus and ethmoid sinus (E/M ratio), visual analogue scale (VAS) score, Lund-Kennedy endoscopic score, and other common clinical indicators to elucidate the clinical characteristics of each cluster. Statistical analysis was conducted using GraphPad Prism 9.5 software.Results:Hierarchical clustering analysis identified four main clusters (Cluster A1-A4), showcasing distinct characteristics such as mild nasal polyps with higher peripheral blood cytokines levels, nasal polyps accompanied by allergies and asthma, a subtype of nasal polyps with high recurrence rates dominated by neutrophils, and nasal polyps with high eosinophil levels. Further subset clustering revealed two clusters of mild polyps (Cluster B1-B2) featuring high cytokine expression and comorbid AR; and two clusters of severe polyps (Cluster B3-B4) presented with severe symptoms, high Lund-Mackay CT score, and high Lund-Kennedy endoscopic score. Variations between Cluster B3 and B4 included symptom complexity, the degree of eosinophil infiltration, and the probability of comorbid asthma. Further clustering analysis for eosinophilic nasal polyps revealed a cluster characterized by highly neutrophilic infiltration and recurrent nasal polyps. The comprehensive analysis of multi-index correlations demonstrated valuable insights into the relationships between common clinical parameters of nasal polyps, providing valuable information for a deeper understanding of the pathogenesis of CRSwNP.Conclusion:The clustering analysis in this study categorizes CRSwNP patients into different clusters based on clinical features and disease outcomes, providing a new perspective for more precise clinical treatment strategies.

Objective: To systematically introduce the design of case-cohort study and the statistical methods of relative risk estimation and their application in the design. Methods: First, we introduced the basic principles of case-cohort study design. Secondly, Prentice's method, Self-Prentice method and Barlow method were described in the weighted Cox proportional hazard regression models in detail, finally, the data from the Shanghai Women's Health Study were used as an example to analyze the association between obesity and liver cancer incidence in the full cohort and case-cohort sample, and the results of parameters from each method were compared. Results: Significant association was observed between obesity and risk for liver cancer incidence in women in both the full cohort and the case-cohort sample. In the Cox proportional hazard regression model, the partial regression coefficients of the full cohort and the case-cohort sample fluctuated with the adjustment of confounding factors, but the hazard ratio estimates of them were close. There was a difference in the standard error of the partial regression coefficient between the full cohort and the case-cohort sample. The standard error of the partial regression coefficient of the case-cohort sample was larger than that of the full cohort, resulting in a wider 95% confidence interval of the relative risk. In the weighted Cox proportional hazard regression model, the standard error of the partial regression coefficient of Prentice's method was closer to the parameter estimates from full cohort than Self-Prentice method and Barlow method, and the 95% confidence interval of hazard ratio was closer to that of the full cohort. Conclusions: Case-cohort design could yield parameter results closer to the full cohort by collecting and analyzing data from sub-cohort members and patients with the disease, and reduce sample size and improve research efficiency. The results suggested that Prentice's method would be preferred in case-cohort design.
China/epidemiology* ; Cohort Studies ; Female ; Humans ; Proportional Hazards Models ; Risk ; Sample Size

Objective To explore the theories, content and approaches of integrating physical activity in children's eye health service system in the context of health services. Methods From the perspectives of six building blocks of WHO health system, namely, leadership and governance, financing, human resources for health, service delivery, medical technology, and health information system, we analyzed the policy framework and key contents related to school-based eye health and physical activity, and explored how to promote the implementation of physical activity into the school-based eye health service system, and the integration of physical activity into the eye health continuum: prevention, intervention, rehabilitation, and health promotion. Results In perspective of health system, the integration of physical activity into school-based eye health services should be in accordance with the five principles of cross-cutting health services, namely, universal accessibility and equity, human rights, evidence-based, life-span, and empowerment. According to the World Vision Report, WHO advocates to build a person-centered eye health service system, and person-centeredness is the core concept of the new model of school-based eye health services and physical activity integration. WHO advocates a school-based approach to education and physical activity in health-promoting schools to promote student health, physical activity as a preventive, interventional, rehabilitation and health promotive measure related to children's eye health, and vigorously train professionals within schools who have knowledge and skills related to physical activity and eye health, build an information system on physical activity and children's eye health, and promote the integration of physical activity into the school-based eye health service system. Conclusion Physical activity is an important measure to promote children's eye health and an important component to achieve a person-centered eye health service system. Based on the six building blocks of the WHO health service system, a school-based eye health service that integrates a theoretical and methodological system of physical activity is constructed, requiring the provision of health promotion methods such as education and physical activity in the school setting, to enhance leadership and governance of eye health services based on educational and physical activity approaches in the school setting, establish new funding mechanisms, provide financial security, develop human resources related to physical activity for eye health, improve related service delivery systems, develop high-quality physical activity intervention eye health techniques and equipment, and integrate information on children's physical activity and eye health into school health information systems to achieve children's eye health and promote their physical and mental development.

Aim To study the combination of lysinespecifc demethylase 1 (lysine-specifc demethylase 1, LSD1) inhibitor pargyline and the chemotherapy drug doxorubicin on the proliferation, migration and invasion of murine triple negative breast cancer 4T-1 cells. Methods In vitro, the effect on the proliferation, invasion and migration of 4T-1 cells of the combination of these two drugs were detected with CCK-8 method, lactate dehydrogenase release test, Chou-Talay method, Scratch test, Transwell assay, Western blot and etc. Tumor-bearing mice were used to investigate the combined effect of these two drugs on the proliferation of 4T-1 cells in vivo. Results The combination of pargyline and doxorubicin effectively inhibited the proliferation, migration and invasion of 4T-1 cells. Compared with single drug group, the combination of these two drugs could significantly inhibit the proliferation of breast cancer and prolong the survival time of mice with triple negative breast cancer. Conclusions The combined application of pargyline and doxorubicin has a synergistic inhibitory effect on the proliferation, migration and invasion of mouse breast cancer 4T-1 cells, and has potential value for clinical treatment on triplenegative breast cancer.

Objective: To investigate the effect of insertion technique and electrode array type on the insertion force of electrode array, and to provide a basis for further optimizing electrode design and facilitating mini-invasive electrode insertion. Methods: Three types of electrode array from Nurotron (Standard Electrode, Slim-medium Electrode, Slim-long Electrode) were studied. from July 2019 to December 2019. These electrode arrays were inserted into the phantom models of the cochlea, manually or robot-assisted(medium speed and low speed). The real-time force during electrode array insertion was recorded by ATI Nano 17 Ti sensors and was analyzed by accessory software. Origin 2020b software was used for statistical processing. Results: The insertion force of all electrode arrays progressively increased with the insertion depth. With the manual technique, the peak force of slim-medium electrode insertion was significantly smaller than that of the standard electrode insertion((71.0±16.6) mN vs (140.9±52.7) mN, Z=3.683, P<0.01), and the peak force of the slim-long electrode insertion was between the peak force of standard electrode and slim-medium electrode(P>0.05). No difference was found in the force variation of insertion among the three electrodes(P>0.05). With medium-speed and low-speed robotic assistance, the peak force characteristics of three electrodes were similar to those with the manual technique, but the force variation of standard electrode insertion ((83.9±9.7) mN/s) at medium speed was significantly larger than that of the slim-long electrode insertion ((69.2±4.0)mN/s), and the force variation of the standard electrode insertion at low speed was significantly greater than the other two electrodes. For the same electrode, robot-assisted insertion presented significantly lower peak force and force variation than manual insertion for each type of electrode array. But there was no difference in the peak force and force variation between two-speed levels of robot assistance (P>0.05). Conclusions: The insertion force of the electrode array will be lower when a slim electrode array or robot technique is applied. Long electrode array might make manual insertion difficult or less precise. Robot assistance has advantage on force control during electrode array insertion.
Cochlea/surgery* ; Cochlear Implantation ; Cochlear Implants ; Electrodes, Implanted ; Humans ; Robotics

OBJECTIVES: To study the transcriptomic changes of astrocytes in the brain of rats exposed to methamphetamine (METH) and its possible mechanism in neurotoxicity. METHODS: The rats were intraperitoneally injected with METH (15 mg/kg) every 12 h for 8 times in total to establish the subacute rat model of METH. After the model was successfully established, the striatum was extracted, and astrocytes were separated by the magnetic bead method. Transcriptome sequencing was performed on selected astrocytes, and the differentially expressed genes were analyzed by gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. RESULTS: A total of 876 differentially expressed genes were obtained by transcriptome sequencing, including 321 up-regulated genes and 555 down-regulated genes. GO analysis revealed that differentially expressed genes were mainly concentrated in cell structure, biological process regulation, extracellular matrix and organelle functions. KEGG pathway enrichment analysis showed that steroids biosynthesis, fatty acid biosynthesis, peroxisome proliferators-activated receptor (PPAR), adenosine 5'-monophosphate-activated protein kinase (AMPK) and other signaling pathways were significantly changed. CONCLUSIONS METH can cause structural changes of astrocytes through multiple targets, among which cellular structure, steroids biosynthesis and fatty acid biosynthesis may play an important role in nerve injury, providing a new idea for forensic identification of METH related death.
Animals ; Astrocytes ; Brain ; Gene Expression Profiling ; Methamphetamine/pharmacology* ; Rats ; Signal Transduction ; Transcriptome

Objective:To discusses effectiveness of CTA in the classification of first plantar metatarsal artery and its application value in thumb reconstruction.Methods:Thirty-six cases who underwent thumb reconstruction with free second toe or hallucis flap between December, 2015 and December, 2018 were retrospectively analyzed. Among these cases, 22 cases were injured by machine stranding, 7 cases by heavy objects, and 7 cases were injured by rolling. Exact first plantar metatarsal arteries of all these cases were evaluated by using CTA preoperatively. And compared with intraoperative findings at the donor sites. Free first or second toe flap for thumb reconstruction were designed preoperatively based on branching pattern of first plantar metatarsal arteries.Results:The origin, course, 3-dimensional (3D) anatomical relationship with surrounding tissues and branching pattern of all these feet first plantar metatarsal arteries of 35 cases (70 feet)were well displayed in CTA images, and 1 case (2 feet) were showed poor vascular continuity and artifacts in CTA (2.78%). According to the branching pattern of first plantar metatarsal arteries, 29 cases (58 feet, 80.56%) were ramifying type, 5 cases (10 feet, 13.88%) were main trunk type, and 1 case (2 feet, 2.78%) were tiny branch type. Preoperative CTA images and intraoperative findings at the donor site of 35 cases were remarkably consistent. According to CTA images, 27 cases underwent thumb reconstruction with hallucis flap, 8 cases underwent thumb reconstruction with second toe, and 1 case of poor vascular continuity and artifacts in CTA underwent thumb reconstruction with hallucis flap eventually. All these cases were followed-up for 6-24 (average 12) months, and all reconstructed thumbs survived. The clinical outcomes of all these reconstructed thumbs were good with satisfactory appearance, sensory recovery, excellent motion. The donor feet of all cases recovered well.Conclusion:High-quality 3D images of first plantar metatarsal arteries could be obtained by CTA, allowing preoperative assessment of blood supply and planning of donor site. Therefore, success rate of reconstructed operation could be improved with low disability rate of donor site.

OBJECTIVE: To explore and compare the safety depths of perpendicular and oblique acupuncture at Yamen (GV 15) in patients with atlantoaxial dislocation (AAD) and healthy volunteers. METHODS: One bundred and seventy-seven patients with atlantoaxial dislocation were selected as an AAD group, and 207 patients without atlantoaxial dislocation and with normal anatomical structure were selected as a normal group. All participants were moderately sized. The MRI scanning of the cervical vertebra was performed, and the safety depth of perpendicular and oblique acupuncture at Yamen (GV 15) was calculated on the sagittal image. RESULTS: In the AAD group, the safety depth of men was (45.33±5.17) mm for perpendicular acupuncture and (48.58±4.41) mm for oblique acupuncture; the safety depth of women was (44.17±7.80) mm for perpendicular acupuncture and (47.49±7.32) mm for oblique acupuncture. In the normal group, the safety depth of men was (47.72±5.06) mm for perpendicular acupuncture and (42.69±5.53) mm for oblique acupuncture; the safety depth of women was (44.63±5.85) mm for perpendicular acupuncture and (39.88±6.18) mm for oblique acupuncture. The safety depth of men and women for oblique acupuncture was longer than that for perpendicular acupuncture in the AAD group (<0.01); the safety depth of men and women for oblique acupuncture was shorter than that for perpendicular acupuncture in the normal group (<0.01). The safety depth of perpendicular and oblique acupuncture between men and women was not significant in the AAD group (>0.05); the safety depth of perpendicular and oblique acupuncture for men was longer than that for women in the normal group (<0.01). For men, the safety depth of perpendicular acupuncture in the AAD group was shorter than that in the normal group (<0.01), while the safety depth of oblique acupuncture in the AAD group was longer than that in the normal group (<0.01). For women, the safety depth of perpendicular acupuncture in the AAD group was similar with that in the normal group (>0.05), while the safety depth of oblique acupuncture in the AAD group was longer than that in the normal group (<0.01). CONCLUSION The safe depth of acupuncture at Yamen (GV 15) has significantly changed under AAD, so during the clinical acupuncture the needle insertion should be less than its safe depth.
Acupuncture Points ; Acupuncture Therapy ; Cervical Vertebrae ; Female ; Humans ; Joint Dislocations ; therapy ; Male ; Neck Injuries ; therapy ; Needles