[Standardized diagnosis and treatment of colorectal polyps].

This article explores the standardized management of colorectal polyps, including classification, treatment, follow-up, and preventive control. Corresponding treatment strategies, including endoscopic resection and surgical intervention, are employed for different types of polyps. Currently, there is debate over whether to choose endoscopic resection or surgical intervention for malignant polyps at pT1 stage. Drawing on the latest literature and guidelines, the article elaborates on polyp classification, treatment modalities, follow-up, and preventive measures. Standardized management of colorectal polyps is important for reducing the incidence of colorectal cancer and improving the cure rate of early-stage colorectal cancer.

[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.

[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.

[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.

[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.

[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.

[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.

The impact of NudCD1 on renal carcinoma cell proliferation, migration, and invasion.

OBJECTIVE: Renal cell carcinoma (RCC) is the most common malignant tumor in the urogenital system. Its easily metastatic characteristics greatly reduce the postoperative survival rate. NudCD1, as a proto-oncogene, may be involved in the proliferation, migration, and invasion of renal cell carcinoma cell. This study intends to explore the expression of NudCD1 in renal cancer tissue and its effect on renal cell behavior. PATIENTS AND METHODS: NudCD1 expression in RCC tissue was tested Western blot. The cellular localization of NudCD1 was detected by immunohistochemistry (IHC). NudCD1 highly expressed RCC cell line was selected. NudCD1 knockdown or overexpression was performed through cell transfection. Cell proliferation, migration, and invasion were assessed by MTT assay, wound scratch assay, and transwell assay, respectively. RESULTS: NudCD1 mainly located in the cytoplasm and significantly upregulated in RCC tissue compared with adjacent normal control (p < 0.05). NudCD1 expressed highest in A498 cell line among several RCC cell lines. NudCD1 expression was positively correlated with cell proliferation, migration, and invasion in A498. NudCD1 may be treated as a key factor in regulating cell behavior. CONCLUSIONS: NudCD1 significantly increased in RCC and was positively correlated with cell proliferation, migration, and invasion. It could be used as an indicator for the early screening and potential treatment target for RCC.

Role of Th1/Th2 cytokines in the diagnosis and prognostic evaluation of ankylosing spondylitis.

Ankylosing spondylitis (AS), a progressive disease of the spine, manifests as peripheral arthritis with tendon and ligament inflammation that restricts activity. AS is a rheumatoid autoimmune disease although the rheumatoid factor is absent in patients with AS. It is characterized by inflammatory changes such as elevated levels of serum inflammatory factors. The roles of Th1 and Th2 cytokines in autoimmune diseases are well known. However, the roles of these cytokines in the diagnosis and prognosis of AS is poorly understood. The aim of this study was to investigate the roles of Th1/Th2 cytokines in the diagnosis and prognosis of AS. The BASDAI activity, BASFI functional index, BASMI measurement score, and the levels of CRP and ESR were measured during the treatment of patients with active AS. The levels of IFN-γ and TNF-α (Th1 cytokines) and IL-4 and IL-10 (Th2 cytokines) were quantified. The levels of IL-4 and IL-10 were significantly low in the serum of patients with active AS, who also had high IFN-γ and TNF-α levels compared to those in the control individuals (P < 0.05). After treatment, the levels of IL-4 and IL-10 increased while those of IFN-γ and TNF-α decreased compared to those in individuals with active AS (P < 0.05). The disease activity index correlated positively with levels of IFN-γ and TNF-α and negatively with levels of IL-4 and IL-10, but not with that of CRP or ESR. Changes in the levels of Th1/2 cytokines in patients with AS may reflect disease activity and prognosis.

[Simultaneous triple semicircular canal plugging and cochlear implantation in advanced Meniere's disease].

Objective: To evaluate the feasibility of combining simultaneous triple semicircular canal plugging (TSCP) and cochlear implantation (CI) to treat vertigo and hearing loss in advanced Meniere's disease(MD) patients, so as to provide an alternative surgical procedure for treating this disorder. Methods: Data from seven patients, who were referred to our hospital and diagnosed with unilateral MD strictly meeting the criteria issued by Chinese Academy of Otolaryngology-Head and Neck Surgery Committee (2006), from Jan. 2015 to Jan. 2016, were retrospectively analyzed in this work. Seven patients, in whom the standardized conservative treatment had been given for at least one year and frequent vertigo still occurred, underwent simultaneous TSCP and CI under general anesthesia via mastoid approach. Postoperative follow-up time was more than six months. Vertigo control and auditory function were measured. Pure tone audiometry, speech perception scores, caloric test, head impulse test (HIT), and vestibular evoked myogenic potential (VEMP) were performed for evaluation of audiological and vestibular functions. Results: All patients had bilateral severe sensorineural hearing loss preoperatively. One side hearing loss was due to MD and another side was due to reasons including sudden sensorineural hearing loss, mumps and other unknown reason. The total control rate of vertigo in seven MD patients was 100.0% in the six-month follow-up, with complete control rate of 85.7% (6/7) and substantial control rate of 14.3% (1/7). Improved hearing threshold and speech perception scores were observed in all study participants. Postoperative average aided hearing threshold was 32.5 dBHL, the average monosyllabic word score was 42.6% and speech perception scores of sentences tested in quiet was 52.3%. Tinnitus improved in five cases, and no significant change in two patients. Post-operatively, all patients suffered from temporary vertigo and balance disorders. Vertigo was disappeared in all patients within 3-5 days, while, an average recovery time of balance disorders was 19.7 days. Six months after treatment, loss of semicircular canal function by caloric test was found in the operation side of all patients and no change in cVEMP or oVEMP test was noted. All patients had no facial paralysis, cerebrospinal fluid leakage, and other complications. Conclusions: A combined approach of TSCP and CI which could control vertigo effectively and improve hearing loss and tinnitus represents an effective and safe therapy for some advanced MD patients.

Discovery of differentially expressed genes in cashmere goat (Capra hircus) hair follicles by RNA sequencing.

The mammalian hair follicle (HF) is a unique, highly regenerative organ with a distinct developmental cycle. Cashmere goat (Capra hircus) HFs can be divided into two categories based on structure and development time: primary and secondary follicles. To identify differentially expressed genes (DEGs) in the primary and secondary HFs of cashmere goats, the RNA sequencing of six individuals from Arbas, Inner Mongolia, was performed. A total of 617 DEGs were identified; 297 were upregulated while 320 were downregulated. Gene ontology analysis revealed that the main functions of the upregulated genes were electron transport, respiratory electron transport, mitochondrial electron transport, and gene expression. The downregulated genes were mainly involved in cell autophagy, protein complexes, neutrophil aggregation, and bacterial fungal defense reactions. According to the Kyoto Encyclopedia of Genes and Genomes database, these genes are mainly involved in the metabolism of cysteine and methionine, RNA polymerization, and the MAPK signaling pathway, and were enriched in primary follicles. A microRNA-target network revealed that secondary follicles are involved in several important biological processes, such as the synthesis of keratin-associated proteins and enzymes involved in amino acid biosynthesis. In summary, these findings will increase our understanding of the complex molecular mechanisms of HF development and cycling, and provide a basis for the further study of the genes and functions of HF development.

[Effects of miR-93 on proliferation and apoptosis of osteosarcoma cells].

Objective: To investigate the effects of miR-93 on proliferation and apoptosis of osteosarcoma cells and the possible mechanism. Methods: The expression levels of miR-93 and the naked cuticle homolog 2 (NKD2) in 6 osteosarcoma cell lines (143B, HuO9, Saos2, MG63, U2OS and G292) and one osteoblast cell line hFOB1.19 were determined by quantitative real-time PCR and Western blot assays, respectively. MiR-93 down-regulated 143B and HuO9 cells were constructed by lipofection transfection, and their proliferation and apoptosis were detected by MTT and flow cytometry assays, respectively. Luciferase reporter assay was used to determine whether the 3'UTR of NKD2 mRNA was a binding target of miR-93. In addition, 143B cells were transfected with NKD2 cDNA, and the effects of NKD2 on proliferation and apoptosis of osteosarcoma cells were investigated. Results: Up-regulation of miR-93 and down-regulation of NKD2 were detected in osteosarcoma cell lines. MTT and flow cytometry assays showed that miR-93 promoted proliferation and inhibited apoptosis in osteosarcoma cells. Luciferase assay confirmed that miR-93 targeted NKD2 directly. In addition, overexpression of NKD2 inhibited proliferation and promoted apoptosis of osteosarcoma cells were found. Conclusions: MiR-93 targets NKD2 to promote proliferation and inhibit apoptosis of osteosarcoma cells. The findings may have significant implications in the diagnosis and treatment of osteosarcoma.

Functional properties of a new low-molecular-weight glutenin subunit gene from a bread wheat cultivar.

Some allelic forms of low-molecular-weight glutenin subunit (LMW-GS) can greatly influence the end-use of wheat flours, understanding the function of each allele of LMW-GS is important to wheat quality breeding. A LMW-GS gene XYGluD3-LMWGS 1(AY263369) has been cloned from bread wheat cultivar Xiaoyan 6. The deduced protein contained nine cystine residues, one more than that in all other LMW-GSs reported previously, indicating that it is either a new gene or a new allele of a known LMW-GS gene. In this study, the gene was expressed in E. coil in large scale for the testing of its functional property. Reactive Red 120-Agarose resin was used efficiently to purify the expressed LMW-GS proteins from bacteria, with the lactic acid-sodium lactate buffer (pH 4.5) which contained low concentration SDS as elution solution. The purified protein (belonging to the LMW-m family, MW about 35 KDa) was supplemented into a base flour, the results of 10 g dough mixing test indicated that incorporation of the LMW-GS increased the strength of the dough, with significant increases in mixing time (MT) and peak width (PW), and decrease in breakdown in resistance (RBD) compared with the control. In addition, the dough with incorporation of the LMW-GS had more glutenin macropolyeric protein than the control, suggesting that the LMW-GS participated in forming larger glutenin polymers, and greatly contributed to dough strength. The changes in mixing parameters and the amount of glutenin macropolyeric protein were related to the quantity of incorporating subunits.

[Regulatory effect of Bcl-2 on the cortical neurons of primary cultured mice with HSV-1 infection].

OBJECTIVE: To study the effect of Bcl-2 on the cortical neurons of primary cultured mice with HSV-1 infection. METHODS: Analysis of the expression of Bcl-2 on the cortical neurons of primary cultured fetal mice in vitro infected with HSV-1 for 11 hours or exposed to sorbitol for 5 hours was made by flow cytometry and Western blotting. RESULTS: The Bcl-2 of the cultured neurons undergoing HSV-1 infection expressed upregulating compared with the mock untreated neurons. The Bcl-2 protein of HSV-1 infected and exposed to sorbitol neurons expressed upregulating compared with the control group. The Bcl-2 protein of the primary cultured 3 day cells expressed higher than that of the primary cultured 7 day cells. The higher neurovirulence, the higher expression of Bcl-2. CONCLUSIONS: Bcl-2 might protect the primary cultured cortical neurons of fetal mice from apoptosis where infected with HSV-1, and thereby the lifespan of host cells may be prolonged.

Rheumatoid arthritis complicated by pachy- and leptomeningeal rheumatoid nodule-like granulomas and systemic vasculitis.

Rheumatoid nodule is a frequent and characteristic extra-articular manifestation of rheumatoid arthritis (RA). Its involvement of central nervous system is a rare occurrence with only a few reported cases. A 78-year-old man with severe arthritis showing the formation of rheumatoid nodule-like granulomas in the dura and subarachnoid space along with the spleen is presented. The characteristic morphological finding of the granulomas was the presence of neutrophils and the absence of definite fibrinoid necrosis, which differed from the typical features of rheumatoid nodules previously described. The diagnosis should be based on the exclusion of diseases that may cause similar granulomatous reactions including infectious diseases. Additionally, there was systemic necrotizing vasculitis in the dura and multiple cerebral infarcts, although the association between vasculitis and cerebral infarcts was not clear.