[Effects of applying human umbilical cord mesenchymal stem cell exosomes through different pathways to treat full-thickness skin defect wounds in mice].

Objective: To investigate the effects of human umbilical cord mesenchymal stem cell (hUCMSC) exosomes in the treatment of full-thickness skin defect wounds in mice through local wound application, subcutaneous injection at the wound margin, and tail vein injection, and to explore the optimal administration route of hUCMSC exosomes for wound treatment. Methods: This study was an experimental study. hUCMSC exosomes were extracted from the discarded umbilical cord tissue of three normal delivery women aged 25-35 years in the Department of Obstetrics and Gynecology of Baogang Hospital of Inner Mongolia and successfully identified. Totally 120 male BALB/c mice aged 6-8 weeks were selected, and full-thickness skin defect wounds were prepared on the back of them. According to the random number table, the injured mice were divided into control group (without drug administration), local wound application group, wound margin subcutaneous injection group, and tail vein injection group (with 30 mice in each group). Mice in the latter three groups were given 0.2 mL phosphate buffer solution containing 200 µg hUCMSC exosomes by local wound application, subcutaneous injection at the wound margin, and tail vein injection, respectively. On post injury day (PID) 7, 14, and 21, the general condition of the wound was observed, and the wound healing rate was calculated; the wound tissue was collected, the pathological changes and collagen fibers were observed respectively by hematoxylin-eosin staining and Masson staining, the number of new microvessels was observed by CD31 immunohistochemical staining, and the content of tumor necrosis factor α (TNF-α) and interleukin-6 (IL-6) was detected by enzyme-linked immunosorbent assay. The sample number was 10 in each group at each time point. Results: On PID 7, 14, and 21, the wounds of mice in the 4 groups all healed gradually, and the wound healing of the mice in wound margin subcutaneous injection group was the best; the wound healing rates of mice in the three administration groups were significantly higher than those in control group (P<0.05), the wound healing rates of mice in wound margin subcutaneous injection group and tail vein injection group were significantly higher than those in local wound application group (P<0.05), and the wound healing rates of mice in wound margin subcutaneous injection group were significantly higher than those in tail vein injection group (P<0.05). On PID 7, 14, and 21, the growth and epithelialization speed of the wound tissue of mice in the three administration groups were significantly accelerated, and the collagen fibers in the wounds of mice in the three administration groups were larger in number and more neatly arranged in comparison with the control group. On PID 7, 14, and 21, under every 200-fold visual field, the number of new microvessels in the wound tissue of mice in local wound application group was 24.1±2.5, 50.7±4.1, and 44.2±2.3, respectively, the number of new microvessels in the wound tissue of mice in wound margin subcutaneous injection group was 32.2±2.9, 67.5±4.9, and 53.6±3.7, respectively, and the number of new microvessels in the wound tissue of mice in tail vein injection group was 27.8±2.4, 59.1±3.7, and 49.6±2.6, respectively, which was significantly more than 20.6±1.7, 46.7±3.4, and 40.9±2.8 in control group (P<0.05); the number of new microvessels in the wound tissue of mice in wound margin subcutaneous injection group and tail vein injection group was significantly more than that in local wound application group (P<0.05); the number of new microvessels in the wound tissue of mice in wound margin subcutaneous injection group was significantly more than that in tail vein injection group (P<0.05). On PID 7, 14, and 21, the content of TNF-α and IL-6 in the wound tissue of mice in the three administration groups was significantly less than that in control group (P<0.05), the content of TNF-α and IL-6 in the wound tissue of mice in wound margin subcutaneous injection group and tail vein injection group was significantly less than that in local wound application group (P<0.05), and the content of TNF-α and IL-6 in the wound tissue of mice in wound margin subcutaneous injection group was significantly less than that in tail vein injection group (P<0.05). Conclusions: Local wound application, subcutaneous injection at the wound margin, and tail vein injection of hUCMSC exosomes can all promote the wound healing of full-thickness skin defects in mice through alleviating excessive inflammatory response and promoting angiogenesis. Among them, subcutaneous injection at the wound margin has a better therapeutic effect, indicating subcutaneous injection at the wound margin is the optimal administration route for hUCMSC exosomes in wound treatment.

[Multicenter clinical epidemiological analysis of elderly atopic dermatitis in China].

Objective: To investigate and analyze the clinical features of elderly atopic dermatitis (AD) in China. Methods: Based on the National Clinical Research and Homogeneous Diagnosis and Treatment Project for Type 2 Inflammation Dermatosis, a total of 2 281 patients aged 65 years or older were enrolled from 172 grade A tertiary hospitals who were diagnosed as atopic dermatitis from June 2021 to February 2023, and their demographics, clinical feature, and disease severity, etc. were collected. Elderly AD patients were divided into groups based on gender, history of allergic diseases (with or without a personal or family history of allergic diseases), and clinical features (site of onset, AD signs) and scales were compared within the groups. Median (Q1, Q3) was used for quantitative data. Results: The age of 2 281 elderly AD patients was 73.02 (68.83, 79.62) years old, among whom there were 1 649 males (72.29%) and 632 females (27.71%). A total of 2 244 cases were recorded with the information of the onset stage, of whom 1 713 cases (76.34%) occurred in the elderly stage. A total of 2 136 cases were recorded with the information of personal or family history of allergic diseases, of which 1 076 cases (50.37%) had a personal or family history of allergic diseases, and 1 060 (49.63%) had no history of allergic diseases. Skin lesions were predominantly involved in the waist, back, buttocks, and AD signs were mainly eczema-like skin lesions on the cheek and/or scalp and/or limb extension. Patients with moderate to severe AD accounted for 60.58% (1 327 cases), moderate to severe itching accounted for 81.32% (1 781 cases). Patients with anxiety and depression accounted for 46.14% (1 011 cases) and 39.27% (860 cases), respectively. Men had a higher EASI score than women [9.67 (4.77, 19.28) vs 8.45 (3.98, 17.11), P=0.040]. EASI, HADS-anxiety and WI-NRS scores were higher in patients with history of allergic diseases than those without allergy history [ (9.79 (4.84, 19.96) vs 8.96 (4.05, 18.31), P=0.015; 7.22 (3.49, 10.00) vs 6.81 (3.12, 9.33), P=0.012; 7.64 (5.62, 9.07) vs 7.38 (5.35, 8.91), P=0.036]. Conclusion: Elderly AD patients have their own exclusive clinical manifestations, and the understanding of these characteristics is beneficial for guiding clinical development of targeted management plans. Elderly AD patients are mostly senile onset, and male patients are more than female patients, skin lesions are mainly distributed on the extended side, and the disease burden is heavy.

[Characteristics of responsiveness of cochlear nerve to electrical stimulation in patients with cochlear nerve deficiency].

Objectives: This study aimed to evaluate the responsiveness of cochlear nerve to electrical stimulation in patients with cochlear nerve deficiency(CND), to compare their results with those measured in implanted children with normal-sized cochlear nerves, and to investigate the characteristics of the cochlear nerve injury of children with CND. Methods: Participants were children who underwent cochlear implantation at Shandong Provincial ENT Hospital from January 2012 to January 2020, including CND group and control group. The CND group included 51 subjects (male:20; female: 31) who were diagnosed with CND and had normal cochlea. For the CND group, four children had been bilaterally implanted, the mean implantation age was (2.7±1.5) years old. The control group included 21 subjects (male:10; femal:11) who had normal-sized cochlear nerve and normal cochlea. For the control group, all children had been unilaterally implanted except one, and the mean implantation age was (3.0±1.9)years old. Three subjects in the CND group used CI422 electrode arrays, and all the other subjects used CI24RECA/CI512 electrode arrays. The electrically evoked compound action potentials (ECAP) had been tried to record for each electrode using Custom Sound EP software (v. 4.3, Cochlear Ltd.) at least six months post first activation. Furthermore, ECAP amplitude growth functions (AGF) were measured at multiple electrode locations across the electrode array. Generalized linear mixed effect models with the subject group and electrode location as the fixed effects and subjects as the random effect were used to compare results of ECAP measurements. Results: In the control group, ECAP could been recorded at all electrodes (100%), but it could only be recorded in 71% (859/1 210) electrodes in the CND group. Additionally, the percentage of electrodes with measurable ECAP decreased from electrode 1 to electrode 22 in the CND group. Compared to the control group, the ECAP thresholds significantly increased, the ECAP amplitudes and AGF slopes significantly decreased, and the ECAP latency significantly increased in the CND group (P<0.01). GLMM showed that the stimulating site had a significant effect on the ECAP threshold, maximum amplitude, and AGF slope (P<0.01), but had no significant effect on the ECAP latency (P>0.05) in the CND group. However, the stimulating site had no significant effects on the ECAP measurements in the control group. Furthermore, the functional status of cochlear nerve varied greatly among CND group. From electrode 1 to electrode 22, the ECAP thresholds gradually increased, the ECAP maximum amplitudes and AGF slopes gradually decreased in the CND group. Conclusion: Compared with patients with normal-sized cochlear nerve, not only the number of residual spinal ganglion neurons reduce,but also the function of spinal ganglion neurons damages in CND patients. The degree of cochlea nerve deterioration varies greatly among CND patients. Generally, the deterioration of cochlear nerve tends to increase from the basal to the apical site of the cochlea.

[Short-course radiotherapy combined with CAPOX and PD-1 inhibitor for the total neoadjuvant therapy of locally advanced rectal cancer: the preliminary single-center findings of a prospective, multicentre, randomized phase II trial (TORCH)].

Objective: Total neoadjuvant therapy has been used to improve tumor responses and prevent distant metastases in patients with locally advanced rectal cancer (LARC). Patients with complete clinical responses (cCR) then have the option of choosing a watch and wait (W&W) strategy and organ preservation. It has recently been shown that hypofractionated radiotherapy has better synergistic effects with PD-1/PD-L1 inhibitors than does conventionally fractionated radiotherapy, increasing the sensitivity of microsatellite stable (MSS) colorectal cancer to immunotherapy. Thus, in this trial we aimed to determine whether total neoadjuvant therapy comprising short-course radiotherapy (SCRT) combined with a PD-1 inhibitor improves the degree of tumor regression in patients with LARC. Methods: TORCH is a prospective, multicenter, randomized, phase II trial (TORCH Registration No. NCT04518280). Patients with LARC (T3-4/N+M0, distance from anus ≤10 cm) are eligible and are randomly assigned to consolidation or induction arms. Those in the consolidation arm receive SCRT (25Gy/5 Fx), followed by six cycles of toripalimab plus capecitabine and oxaliplatin (ToriCAPOX). Those in the induction arm receive two cycles of ToriCAPOX, then undergo SCRT, followed by four cycles of ToriCAPOX. Patients in both groups undergo total mesorectal excision (TME) or can choose a W&W strategy if cCR has been achieved. The primary endpoint is the complete response rate (CR, pathological complete response [pCR] plus continuous cCR for more than 1 year). The secondary endpoints include rates of Grade 3-4 acute adverse effects (AEs) etc. Results: Up to 30 September 2022, 62 patients attending our center were enrolled (Consolidation arm: 34, Induction arm:28). Their median age was 53 (27-69) years. Fifty-nine of them had MSS/pMMR type cancer (95.2%), and only three MSI-H/dMMR. Additionally, 55 patients (88.7%) had Stage III disease. The following important characteristics were distributed as follows: lower location (≤5 cm from anus, 48/62, 77.4%), deeper invasion by primary lesion (cT4 7/62, 11.3%; mesorectal fascia involved 17/62, 27.4%), and high risk of distant metastasis (cN2 26/62, 41.9%; EMVI+ 11/62, 17.7%). All 62 patients completed the SCRT and at least five cycles of ToriCAPOX, 52/62 (83.9%) completing six cycles of ToriCAPOX. Finally, 29 patients achieved cCR (46.8%, 29/62), 18 of whom decided to adopt a W&W strategy. TME was performed on 32 patients. Pathological examination showed 18 had achieved pCR, four TRG 1, and 10 TRG 2-3. The three patients with MSI-H disease all achieved cCR. One of these patients was found to have pCR after surgery whereas the other two adopted a W&W strategy. Thus, the pCR and CR rates were 56.2% (18/32) and 58.1% (36/62), respectively. The TRG 0-1 rate was 68.8% (22/32). The most common non-hematologic AEs were poor appetite (49/60, 81.7%), numbness (49/60, 81.7%), nausea (47/60, 78.3%) and asthenia (43/60, 71.7%); two patients did not complete this survey. The most common hematologic AEs were thrombocytopenia (48/62, 77.4%), anemia (47/62, 75.8%), leukopenia/neutropenia (44/62, 71.0%) and high transaminase (39/62, 62.9%). The main Grade III-IV AE was thrombocytopenia (22/62, 35.5%), with three patients (3/62, 4.8%) having Grade IV thrombocytopenia. No Grade V AEs were noted. Conclusions: SCRT-based total neoadjuvant therapy combined with toripalimab can achieve a surprisingly good CR rate in patients with LARC and thus has the potential to offer new treatment options for organ preservation in patients with MSS and lower-location rectal cancer. Meanwhile, the preliminary findings of a single center show good tolerability, the main Grade III-IV AE being thrombocytopenia. The significant efficacy and long-term prognostic benefit need to be determined by further follow-up.

[A clinical application study of digital manufacturing simple intraoral Gothic arch-tracing device in determining the centric relation of complete dentures].

OBJECTIVE: To verify the consistency between the digital manufacturing simple intraoral Gothic arch-tracing device and the traditional intraoral Gothic arch-tracing device in determining the centric relation of complete dentures restoration. METHODS: Ten outpatients with edentulous jaws were selec-ted, and the centric relation of the patients was determined by digital manufacturing of simple intraoral Gothic arch-tracing device (T1) and traditional intraoral Gothic arch-tracing device (T2); the difference of clinical operation time between the two methods was recorded; the upper and lower edentulous jaw plaster models were scanned with two kinds of centric relation, the Standard Triangle Language (STL) files imported into Geomagic studio software to apply the best fitting of multiple points of the both upper jaw models, the fitted STL files imported into the 3 shape viewer software, and the maximum position deviations of the vertical, labial (buccal) and lingual directions of the mandibular midline area and molar areas in T1 and T2 groups measured. During the clinical complete dentures try-in, we observed whether there was midline deviation in the mouth of T1 group and T2 group, and whether the occlusion of posterior teeth was stable or not. RESULTS: The mean time spent on determining the centric relation of T1 and T2 groups was (41.90±2.64) min, (57.50±2.37) min respectively. Paired t test was conducted in the two groups, P < 0.01 with significant statistical difference; The mean maximum position deviation between T1 group and T2 group of the midline mandibular region in labial lingual direction was (0.32±0.14) mm, that was (0.40±0.23) mm in vertical direction; the mean maximum position deviation of molar area in buccal lingual direction was (0.35±0.23) mm and that was (0.33±0.20) mm in vertical direction. In the vertical and horizontal directions, the maximum position deviation of mandibles between group T1 and group T2 was controlled within 0.5 mm. In the process of clinical complete dentures try-in, there was no deviation from the center line of dentures. There was not warping, swinging and other poor stability phenomena in T1 and T2 groups. CONCLUSION: The digital manufacturing of simple intraoral Gothic arch-tracing device can be used to determine the centric relation of complete dentures, which can not only save time of clinical operation, but also ensure the accuracy of the centric relation.

[3D-printed vertebral body in anterior spinal reconstruction after total spondylectomy for patients with cervical chordoma].

OBJECTIVE: To investigate whether 3D-printed artificial vertebral body can reduce prosthesis subsidence rate for patients with cervical chordomas, through comparing the rates of prosthesis subsidence between 3D printing artificial vertebral body and titanium mesh for anterior spinal reconstruction after total spondylectomy. METHODS: This was a retrospective analysis of patients who underwent surgical treatment for cervical chordoma at our hospital from March 2005 to September 2019. There were nine patients in the group of 3D artificial vertebral body (3D group), and 15 patients in the group of titanium mesh cage (Mesh group). The patients' characteristics and treatment data were extracted from the medical records, including age, gender, CT hounsfield unit of cervical vertebra and surgical information, such as the surgical segments, time and blood loss of surgery, frequency and degree of prosthesis subsidence after surgery. Radiographic observations of prosthesis subsidence during the follow-up, including X-rays, CT, and magnetic resonance imaging were also collected. SPSS 22.0 was used to analysis the data. RESULTS: There was no significant difference between the two groups in gender, age, CT hounsfield unit, surgical segments, time of surgery, blood loss of posterior surgery and total blood loss. Blood loss of anterior surgery was 700 (300, 825) mL in 3D group and 1 500 (750, 2 800) mL in Mesh group (P < 0.05). The prosthesis subsidence during the follow-up, 3 months after surgery, there was significant difference between the two groups in mild prosthesis subsidence (P < 0.05). The vertebral height of the 3D group decreased less than 1 mm in eight cases (no prosthesis subsidence) and more than 1 mm in one case (mild prosthesis subsidence). The vertebral height of the Mesh group decreased less than 1 mm in five cases (no prosthesis subsidence), and more than 1 mm in eight cases (mild prosthesis subsidence). Two patients did not have X-rays in 3 months after surgery. There was a statistically significant difference between the two groups in the prosthesis subsidence rate at the end of 12 months (P < 0.01). The vertebral height of eight cases in the 3D group decreased less than 1 mm (no prosthesis subsidence) and one case more than 3 mm (severe prosthesis subsidence). Four of the 15 cases in the Mesh group decreased less than 1 mm (no prosthesis subsidence), two cases more than 1 mm (mild prosthesis subsidence), and nine cases more than 3 mm (severe prosthesis subsidence). There was a statistically significant difference between the two groups in the prosthesis subsidence rate at the end of 24 months (P < 0.01). The vertebral height of seven cases in the 3D group decreased less than 1 mm (no prosthesis subsidence), one case more than 3 mm (severe prosthesis subsidence), and one case died with tumor. One case in the Mesh group decreased less than 1 mm (no prosthesis subsidence), one case more than 1 mm (mild prosthesis subsidence), 11 case more than 3 mm (severe prosthesis subsidence), one case died with tumor and one lost the follow-up. Moreover, at the end of 12 months and 24 months, there was significant difference between the two groups in severe prosthesis subsidence rate (P < 0.01). CONCLUSION: 3D-printed artificial vertebral body for anterior spinal reconstruction after total spondylectomy for patients with cervical chordoma can provide reliable spinal stability, and reduce the incidence of prosthesis subsidence after 2-year follow-up.

[Short-term observation of electrical acoustic stimulation in patients with low frequency residual hearing after cochlear implant].

Objective: To analyze the effects of electrical acoustic stimulation (EAS) on speech and tone recognition as well as music perception in children with low-frequency residual hearing (LFRH) after cochlear implant (CI). Methods: A total of twelve Mandarin patients with LFRH who underwent unilateral CI from January 2017 to October 2020 were recruited, including 8 males and 4 females. There were 5 cases of pre-lingual deafness and 7 cases of post-lingual deafness. The median age at implantation was 12 years old (3-62 years). All patients had residual hearing (RH) before surgery, wore hearing aid (HA) timely, had an effective rehabilitation and the duration of use of electrical stimulation was 37.0±16.2 months. On the implanted side, the thresholds of 125 Hz and 250 Hz were less than and equal to 80 dB HL after implantation. A two-month follow-up clinical study was conducted with the EAS devices. The EAS effects were evaluated before, immediately after and 2 months after upgrade, including speech recognition rate, tone recognition and music tests. SPSS 23.0 software was used for statistical analysis. Results: A total of ten patients completed a two-month clinical follow-up and efficiency evaluation. Compared to the electrical stimulation, the recognition rate of spondee word significantly decreased after the immediate use of EAS (71.7±4.3 vs 79.6±3.1, P=0.018). Compared to the electrical stimulation as well as immediate use of EAS, the results of sentence in noise, tone in noise, and SRT of sentence in noise were all significantly improved at 2 months after use of EAS (P<0.05). The pitch discrimination was significantly improved at 2 months after the use of EAS compared with that before the use of EAS (P=0.042). Compared with before (P=0.021) and immediately (P=0.017) use of EAS, the ability of rhythm resolution was significantly improved. There were no significant differences in other test results (P>0.05). Conclusions: The low-frequency acoustic information provided by EAS as well as the electrical-acoustic stimulation mode can provide rich auditory cues of speech perception in noise, tone recognition in noise, and musical discrimination for CI subjects. It can promote the improvement of complex listening ability of CI patients undergoing long-term electrical stimulation in a short time and comprehensively improve their hearing capacities.

Analysis of the mechanism of Sophorae Flavescentis Radix in the treatment of intractable itching based on network pharmacology and molecular docking.

OBJECTIVE: Sophorae Flavescentis Radix (Kuh-seng, SFR), a Traditional Chinese Medicine (TCM), is widely used alone or within a TCM formula to treat pruritus, especially histamine-independent intractable itching. In the previous study, potential antipruritic active components of the SFR were screened based on cell membrane immobilized chromatography (CMIC), revealing oxymatrine (OMT) as an antipruritic agent. However, the low oral bioavailability (OB) of OMT cannot explain the antipruritic effect of SFR when administered orally in clinic. In this study, we investigated the antipruritic effects and underlying mechanisms of orally administered SFR. MATERIALS AND METHODS: A network pharmacology and molecular docking were employed to screen the active components of SFR and predict their binding to disease-related target proteins, while the potential mechanisms were explored with Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. The binding energy between components and target proteins was calculated by molecular docking. RESULTS: The SFR-components-targets-intractable itching Protein-Protein Interactions (PPI) network was established, and 22 active components and 42 targets were screened. The GO enrichment analysis showed that the key target genes of SFR were related to nuclear receptors, transcription factors, and steroid hormone receptors. The results of the KEGG enrichment pathway analysis include Hepatitis B, epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor resistance, advanced glycation end product (AGE)-receptor for AGE (RAGE) signaling pathway in diabetic complications, etc. Molecular docking showed that three key target proteins in the network, the vascular endothelial growth factor A (VEGFA), epidermal growth factor receptor (EGFR) and caspase-3 (CASP3), have higher binding activities with inermine, phaseolin and kushenol O, respectively; the binding energy of each pair is stronger than that of the target protein-corresponding inhibitors. CONCLUSIONS: The complexity of the SFR-components-targets-intractable itching network demonstrated the holistic treatment effect of SFR on intractable itching. The partial coherence between results screened by CMIC in the previous study and network pharmacology demonstrated the potential of network pharmacology in active component screening. Inermine screened from both CMIC and network pharmacology is a VEGFA inhibitor, which possibly accounts for the antipruritic effect of orally administered SFR.

[Research advances on the treatment of hydrofluoric acid burns].

Hydrofluoric acid is a highly dangerous and toxic inorganic acid, which is widely used in industrial fields and daily life. The risk of hydrofluoric acid burns is related to hydrofluoric acid mass fraction, duration of exposure to hydrofluoric acid, burn area, burn depth, and burn site, etc. Hydrofluoric acid has strong toxicity and tissue penetration ability. A small area of hydrofluoric acid burns can cause death in a short time. Therefore, improving the understanding of the mechanism of hydrofluoric acid burns and learning how to treat hydrofluoric acid burns in different sites can further improve the cure rate of hydrofluoric acid burns.

[The imaging characteristics and prognosis of patients with cochlear implants whose cochlear nerves are not shown on MRI].

Objective: To analyze the temporal bone CT and inner ear magnetic resonance imaging characteristics of cochlear implant patients with no cochlear nerve display in the inner auditory canal under MRI. To retrospectively analyze the long-term hearing and speech rehabilitation effects of such patients after cochlear implant. And to analyze the correlation between the results of imaging examinations and the postoperative effects of cochlear implant patients with this type of cochlear nerve deficiency. Methods: A total of 88 children with cochlear nerve deficiency, who underwent cochlear implantation in Shandong Provincial ENT Hospital from May 2014 to October 2018, were enrolled. Patients with cochlear malformations were excluded,only the patients with cochlear nerve deficiency whose cochlear structure was normal and no cochlear nerve displayed in inner auditory canal under MRI were enrolled. There were 64 patients, including 4 bilaterally implanted, 68 ears in total, with an average age of (2.8±1.7) years (range 1-6 years) at the time of implantation. The implanted product was Cochlear, including 24RECA and 512 models. All patients underwent inner ear magnetic resonance imaging and temporal bone CT scan before operation. Auditory speech function assessments were performed at 12 months, 24 months, and 36 months after surgery, including categories of auditory performance (CAP), speech intelligibility rating (SIR) and hearing aid threshold test. The imaging evaluation content included the width of the cochlear nerve canal of temporal bone CT, the width of the internal auditory canal, the width of the auditory nerve at the cerebellopontine angle of the inner ear MRI, and the ratio of the facial nerve to the width of the auditory nerve at the cerebellopontine angle. The correlations between the results of postoperative hearing aid hearing threshold, CAP, SIR and imaging results were analyzed. Results: Among the 64 cases of cochlear nerve not shown under MRI, 56 ears with CT data showed that the width of the cochlear nerve canal in temporal bone CT was (0.72±0.30) mm (mean±standard deviation, the same below), and the width of the internal auditory canal was (4.07±1.10) mm; 66 ears with MRI data showed that the diameter of the auditory nerve at the cerebellopontine angle of the inner ear MRI was (1.58±0.27) mm, the diameter of the facial nerve was (1.57±0.27) mm, and the ratio of the diameter of the facial nerve to the auditory nerve was (1.02±0.23). The average hearing thresholds at 12, 24, and 36 months after surgery were (46.8±2.5) dB HL, (40.7±0.8) dB HL, and (36.8±1.5) dB HL, respectively. The preoperative and postoperative CAP scores at 12, 24 and 36 months were (1.0±1.0), (3.8±1.4), (4.5±1.4) and (5.1±0.7) points, respectively. The preoperative and postoperative SIR scores at 12, 24, and 36 months were (1.1±0.3), (1.9±0.9), (2.5±0.9), and (2.9±0.6) points, respectively. The hearing threshold at 24 months after surgery was negatively correlated with the width of the internal auditory canal of temporal bone CT (r=-0.349, P=0.037), and the hearing threshold at 36 months after surgery was positively correlated with the ratio of the diameter of the facial nerve to the auditory nerve at the cerebellopontine angle of the inner ear MRI (r=0.740, P=0.001). Conclusions: Children with cochlear implants whose cochlear nerves are not shown on MRI can benefit from cochlear implantation, and their speech and auditory functions can improve significantly after surgery. The width of the internal auditory canal in the temporal bone CT and the ratio of the diameter of the facial nerve to the auditory nerve at the cerebellopontine angle of the inner ear MRI may be related to the long-term hearing threshold after surgery.

[Sleep status associated with psychological and behavioral problems in adolescents and children].

Objective: To examine whether sleep status and social jet lag are related to the mental health behaviors in children and adolescents, providing a reference for preventing and improving children and adolescents' mental health behaviors. Methods: A large cross-section was conducted in Baoan District, Shenzhen, from April to May 2019. A total of 30 188 adolescents and children in grades 1-12 in 14 schools were included. The growth trajectory and health index questionnaire of primary and secondary school students were designed to evaluate the sleep status. Mental health behavior problems among students were accessed using the parents' and students' versions of the Strengths and Difficulties Questionnaire. After controlling for confounding factors of demographic variables, including gender, age, parental education level, academic performance, learning burden, and noise impact, a multivariate logistic regression model was used for statistical analyses. Results: The sleep duration of four grades students were 90.4％,90.1％, 98.2％, and 98.4％, respectively. 19.9％ did not have a post-lunch nap. 19.6％ had a wake-up delay of more than or equal to 2 h weekend morning. 35.1％ had an inconsistent bedtime and 15.5％ had an inconsistent awakening time. The multivariate logistic regression model showed that compared with 8-9 h, the sleep duration of elementary school juniors at night less than or equal to 7 h, 7-8 h increased the risk of psychological behavior problems. The sleep time more than 9 h was negatively correlated with psychological behavior problems. The sleep duration of elementary school seniors less than or equal to 7 h increased the risk of psychological behavior problems. The sleep duration of middle school and high school students less than or equal to 6 h increased psychological behavior problems. The ORs (95％CI) appeared as 2.53(1.85-3.47), 2.41(1.11-5.25), respectively. The ones with a sleep time more than 9 h also increased the risk, and ORs (95％CI) appeared as 2.37(1.40-4.01), 5.38 (1.79-16.1), respectively. Both the absence of post-lunch nap and the nap time less than 0.5 h were risk factors for psychological behavior problems in primary and middle school students. The nap time over 1-2 h was also a risk factor for high school students' psychological behavior problems. Waking up at irregular times in the morning, going to bed at varying times in the evening, and delaying getting up for more than or equal to 2 h on weekends were all risk factors for psychological and behavioral problems among primary and middle school students. The ORs (95％CI) of psychological behavior problems of elementary school juniors and seniors, middle school and high school students were 2.07 (1.45-2.97), 1.57 (1.09-2.26), 2.66 (2.06-3.44), 2.48 (1.96-3.15), respectively. Conclusions: Sleep duration, no post-lunch sleep, and daily intraindividual variability of sleep is positively associated with poor mental health. Additionally, social jet lag is associated with mental health problems in students. It is noted that delaying sleep within half an hour on the weekends of elementary school juniors is significantly associated with an increase in bad mental behavior.

[Molecular mechanism of zoledronic acid inhibiting angiogenesis by semi flexible binding with vascular endothelial growth factor conformation].

Objective: To study the relationship between zoledronic acid (ZOL) and vascular endothelial growth factor (VEGF) conformation so as to reveal the mechanism of bisphosphonates inhibiting angiogenesis. Methods: The binding structures of ZOL and VEGF were preprocessed and the molecular dockings were simulated through AutoDockTools, Discovery studio4 and AutoDockVina. The best binding conformation was accurately screened. The effects of various concentrations of ZOL (group A was 0 µmol/L, groups B, C and D were 25, 50 and 100 µmol/L, respectively) on human umbilical vein endothelial cell (HUVEC) proliferation, angiogenesis and angiogenic molecules were detected by using cell counting kit-8 (CCK-8) in vivo and in vitro angiogenesis, immunofluorescence and Western blotting. Results: There was a ZOL binding site on the target protein VEGF conformation. The affinity was -5.2 kcal/mol. This binding site consisted of the hydrophobic region composed of amino acids Cys26, 51, 57, etc. and the hydrogen bond binding region of the A chain (ASP34, SER50) and B chain (CYS61, 68, LEU66, GLY59). The results of CCK-8 showed that the levels of value A in groups B, C and D were significantly lower than that in group A at each time point from 3 to 6 days (P<0.05). In vitro vascular experiments demonstrated that the numbers of budding in groups B, C and D [(208±28), (151±21) and (62±9), respectively] were significantly lower than that in group A (276±30) (P<0.05). In vivo vascular experiments displayed that the ratio of Matrigel gel/plasma fluorescence in group A (0.003 1±0.000 3) was significantly higher than those in group B (0.002 1±0.000 2), group C (0.001 6±0.000 2) and group D (0.000 6±0.000 1) (P<0.05). The results of Western blotting revealed that the expression of VEGF in groups B, C and D [(0.72±0.11), (0.41±0.07) and (0.24±0.04), respectively] were significantly lower than that in group A (1.01±0.02) (P<0.05), and the expression levels of hypoxia-inducible factor-1α (HIF-1α) in groups B, C and D [(0.68±0.09), (0.55±0.06) and (0.43±0.08), respectively] were significantly lower than that in group A (0.96±0.04) (P<0.05). Conclusions: ZOL could inhibit cell proliferation, in vivo and in vitro vascularization and expression of VEGF/HIF-1α. The binding site of ZOL with the conformation of VEGF was located in the hydrophobic region and hydrogen-bonding region of amino acids. Designing an antagonist targeting this site might potentially alleviate the effect of ZOL in inhibiting angiogenesis.

[The relationship between migration time and the prevalence of myopia of children and adolescents aged 6-18 years old in Shenzhen].

Objective: To analyze the relationship between migration time and the prevalence of myopia of children and adolescents aged between 6 and 18 years old in Shenzhen. Methods: From April to May 2019, 26 618 children and adolescents from 14 schools in six streets of Baoan District, including Fuyong, Shajing, Xin'an, Xixiang, Songgang and Shiyan, were included in the study by using random cluster sampling method. The demographic characteristics, migration status, self-reported myopia, screen time in the last seven days, outdoor activities in the last one month and other information were collected through the questionnaire. The differences of myopia among children and adolescents with different characteristics were compared by χ2 test, and the relationship between migration time and the prevalence of myopia was analyzed by multivariate unconditional logistic regression model. Results: The age of 26 618 study participants was (12.37±3.49) years old, and the overall prevalence of myopia was 49.4%. Multivariate logistic regression analysis showed that after controlling for relevant confounding factors, compared with migrant children and adolescents of migrant workers who migrated for 1-2 years, those of migrant workers who had migrated for more than 6 years had a higher risk of myopia [OR (95%CI): 1.48 (1.14-1.92)]. After being grouped by phase of school, in the lower grade group of primary school, the children and adolescents of migrant workers who had migrated for more than 6 years had a higher risk of myopia compared with those of migrant workers who migrated for 1-2 years [OR (95%CI): 1.96 (1.20-2.74)]. In the high school group, compared with the children and adolescents of migrant workers who migrated for 1-2 years, those of migrant workers who had migrated for 3-5 years and ≥6 years had a higher risk of myopia [OR (95%CI): 6.03 (1.29-28.15) and 6.52 (1.51-28.11), respectively]. Conclusion: The migration time is related to the prevalence of myopia of the children and adolescents of migrant workers.

Genome-wide association study of fleece traits in Inner Mongolia Cashmere goats.

Inner Mongolia Cashmere goat is a well-known local cashmere goat breed in China. It is famous for excellent fleece quality and a significant advantage in cashmere yield compared to other cashmere goat breeds. In this study, a genome-wide association study was used to investigate fiber length, fiber diameter, and cashmere yield of 192 Inner Mongolia Cashmere goats using the Illumina GoatSNP52K Beadchip panel. We discovered that four single nucleotide polymorphisms (SNPs) reached genome-wide significance levels. These SNPs were located in some genes, e.g. FGF12, SEMA3D, EVPL, and SOX5, possibly related to fleece traits in Inner Mongolia Cashmere goat. Gene ontology enrichment analysis revealed that these genes were enriched in several biological pathways that were involved in hair follicle development in cashmere goats. In summary, the identified significant SNPs and genes provide useful information to explore genetic mechanisms underlying the variation in fleece traits and genomic selection of Chinese cashmere goat.

[Correlation between elevation of brachial artery pulse pressure increased and coronary heart disease in different genders].

Objective: To explore the relationship between elevation of brachial pulse pressure and coronary heart disease in different genders. Methods: A total of 5 116 inpatients with suspected stable coronary heart disease were consecutively enrolled from December 2011 to June 2017 in the Affiliated Hospital of Chengde Medical College, and divided into coronary heart disease group (n=3 694) and non-coronary heart disease group (n=1 422). The clinical data of all inpatients were collected. A binary logistic regression model of coronary heart disease in different genders were separately established. Results: The morbidity of hypertension, dyslipidemia, type 2 diabetes, ischemic stroke and elevated pulse pressure were all higher in the coronary heart disease group than those in the non-coronary heart disease group (all P<0.05). The area under curve (AUC) of pulse pressure in the male group was 0.540, with an optimal diagnostic threshold of 50 mmHg. The AUC of pulse pressure in the female group was 0.612, with an optimal diagnostic threshold of 60 mmHg. Besides hypertension, type 2 diabetes, increase of low-density lipoprotein cholesterol, ischemic stroke, smoking, and aging, elevated pulse pressure was also an independent risk factor for coronary heart disease in both male and female groups (all P<0.05). Additionally, the risk of elevated pulse pressure for coronary heart disease was higher in female group than that of male group (odds ratio (OR): 1.741 vs 1.284, P<0.05). Conclusion: Elevated pulse pressure may be a new risk factor for coronary heart disease, and its risk for coronary heart disease is higher in women than in men.

Circ-ABCB10 accelerates the malignant progression of oral squamous cell carcinoma by absorbing miRNA-145-5p.

OBJECTIVE: Previous studies have confirmed the carcinogenic role of circ-ABCB10 in certain types of tumors. However, the role of circ-ABCB10 in oral squamous cell carcinoma (OSCC) has not been reported yet. This report investigated the biological function of circ-ABCB10 in aggravating the progression of OSCC by absorbing microRNA-145-5p (miRNA-145-5p) as a ceRNA. PATIENTS AND METHODS: Relative levels of circ-ABCB10 and miRNA-145-5p in OSCC tissues and cell lines were determined. The potential relation between circ-ABCB10 level and pathological indexes of OSCC patients was analyzed. Regulatory effects of circ-ABCB10 and miRNA-145-5p on proliferative and migratory capacities of CAL-27 and Tca8113 cells were assessed. The interaction between circ-ABCB10 and miRNA-145-5p was examined through dual-luciferase reporter gene assay and Chi-square test. At last, rescue experiments were carried out to uncover the role of the circ-ABCB10/miRNA-145-5p regulatory loop in regulating the progression of OSCC. RESULTS: Circ-ABCB10 was upregulated in OSCC tissues and cells. OSCC patients expressing a high level of circ-ABCB10 presented worse tumor staging and a higher rate of distant metastasis relative to those with low level. Knockdown of circ-ABCB10 attenuated proliferative and migratory capacities in CAL-27 and Tca8113 cells. Besides, miRNA-145-5p was downregulated in OSCC tissues and cells. The knockdown of miRNA-145-5p accelerated OSCC cells to proliferate and migrate. Dual-luciferase reporter gene assay proved the binding between circ-ABCB10 and miRNA-145-5p. Moreover, the miRNA-145-5p level was negatively correlated to circ-ABCB10 level in OSCC tissues. Rescue experiments indicated that miRNA-145-5p knockdown could reverse the regulatory effects of circ-ABCB10 on viability, colony formation, and migratory capacity in OSCC cells. CONCLUSIONS: Circ-ABCB10 is upregulated in OSCC, which is closely related to tumor staging and distant metastasis of OSCC patients. Circ-ABCB10 aggravates the progression of OSCC by absorbing miRNA-145-5p.

Ultra-fast and probe-free cellulose biosensor for visual detection of Cu2+ ions in biological samples.

Novel, portable, probe-free, liquid cellulose biosensor was explored via a facile one-pot process for Cu2+ ions detection by naked eyes. The as-prepared biosensor displayed specific recognition towards Cu2+ ions in aqueous solution, even in complex urine and serum samples within 10 s, showing fast response characteristic. There is barely any interference on the Cu2+ ions detection by other metal ions or other complex substances in urine and serum, and the corresponding detection limit is as low as 1.185, 1.9309 and 1.9154 ppm, respectively. Moreover, the cellulose biosensor could act as an excellent candidate to sense Cu2+ ions in biological samples including urine and serum from SD rats with satisfying accuracies and biocompatibility. This study exploits a potential application of cellulose in biosensing and monitoring related to Cu2+ ions.

[Analysis of edge morphology of partial veneers made by different processing techniques and materials].

OBJECTIVE: To compare the edge morphology of partial veneers made of different materials by slurry molding, heat-pressed and computer aided design/computer aided manufacturing (CAD/CAM) techniques. METHODS: Thirty premolars with smooth surface and intact enamel were selected and randomly divided into five groups, 6 specimens for each group. Group A were made from feldspathic porcelain (Noritake®) by slurry molding, while Group B were made from lithium disilicate glass ceramic (IPS E.max® Press) by heat-pressed. Group C/D/E were respectively made from feldspar porcelain block (VITA Mark II®), zirconia-reinforced glass ceramic (VITA Suprinity®) and hybrid ceramic with a ceramic-polymer network (VITA Enamic®) by CAD/CAM techniques. All the partial veneers luted with light-cured composite resin. Then the partial veneers were trimmed and polished to achieve the smooth finishing margin, clinical polishing sets were used according to the product descriptions. Scanning electron microscope (SEM) was used to observe the edge morphology of prostheses and the exposure of resin cements. RESULTS: The smooth surface and knife-like edge of the partial veneers could be obtained after bonding, trimming and polishing. The edges of Group A were slightly rough and the width of the exposed adhesive was (106.00±9.17) µm. In Group B, the edges were smoother than Group A, and the exposed wide adhesive strip was visible, which was (138.33±20.59) µm. In Group E, the edges were smooth too, and the width of exposed adhesive strip was (186.00±5.66) µm. The edges of Group C and Group D were rough and uneven, and the adhesive was rarely exposed, they were (50.67±7.51) µm and (65.67±17.90) µm. There were all significant differences between two groups, except Group C and Group D. CONCLUSION: After trimming and polishing in accordance with clinical procedures, the expected knife-like edge can be obtained in all groups. The width of the exposed resin adhesive of each group is different, the order: Mark II/Suprinity < Noritake < E.max Press < Enamic. The edge morphology of partial veneers in different processing technic and materials are different.