OBJECTIVE To evaluate the palatability and chewability of chewable tablets， and provide reference for the quality evaluation of various types of chewable tablets. METHODS Using self-made Glucosamine hydrochloride chewable tablets as the model drug， the quality test was conducted. The in vitro simulation system for chewable tablets was established by using a texture analyzer and rheometer， and an oral simulation experiment was conducted on chewable tablets. The texture analyzer was used to measure the force required for chewing and simulate the static disintegration process of chewable tablets； the rheometer was adopted to measure the viscoelasticity， thixotropy， and deformability of chewable tablets during the chewing process. RESULTS The disintegration time limit， principal component content， and dissolution of self-made Glucosamine hydrochloride chewable tablets all met the limit requirements. The in vitro simulation results of the texture analyzer showed that self-made chewable tablets were easy to chew in both axial and radial directions， and the force required for chewing was within the range of the chewing force of the teeth； chewable tablets could disintegrate at an appropriate time without being chewed and only taken in the oral cavity. The in vitro simulation results of the rheometer showed that the chewable tablets in the oral cavity exhibited a behavior of elasticity as the main factor and viscosity as the secondary factor through the continuous stirring of the tongue， and the viscosity of the chewable tablets gradually decreased with tongue stirring or tooth chewing； when chewing with teeth， the internal force of the chewing tablets decreased， causing plastic deformation and crushing. After being crushed， the shape couldn’t be restored， making it easy to chew and swallow. CONCLUSIONS The combination of texture analyzer and rheometer can be used to simulate the oral chewing process and evaluate the palatability and chewability of self-made Glucosamine hydrochloride chewable tablets. This model can provide reference for the evaluation of various chewable tablets.

Objective:To explore the efficacy and safety of Rivaroxaban in preventing catheter related thrombosis (CRT) in patients with breast cancer who are undergoing central venous catheter chemotherapy, and provide basis for making standardized prevention and treatment strategies.Methods:In this research, a prospective cohort study was adopted, and breast cancer patients who received central venous catheter chemotherapy in Sanhuan Cancer Hospital during September 2020 to March 2022 were selected as a treatment group to take the rivaroxaban anticoagulation therapy with 10 mg.po.qd for one month. The control group got no preventive anticoagulation therapy. Vascular ultrasound examination was taken to confirm the occurrence of CRT, and a chi-square test was done for comparison the disparity between the groups. Logistic regression was applied to analyze the univariate and multivariate factors for the formation of CRT.Results:In the research, a total of 235 patients were selected, and there were a total of 19 035 days of catheterization with 81 days of catheterization on average. While in the control group, the incidence of CRT was 28.0% (33/118), the incidence of CRT in the treatment group was 20.5% (24/117), the difference was no significant ( P=0.183). Subgroup analysis results showed that the peripherally inserted central catheter (PICC) was performed in 165 cases with the CRT incidence of 18.2% (30/165) and thrombosis was mostly seen around axillary vein, accounting for 63.3%. Subclavian vein catheterization was performed in 63 cases with the CRT incidence of 39.7% (25/63), and thrombosis was mostly seen around subclavian vein, accounting for 88.0% (22/25). Implantable venous access port was implanted in 7 cases around subclavian vein and internal jugular vein with the CRT incidence of 28.6% (2/7). The patients who developed CRT within 30 days after catheterization accounted for 54.4% (31/57), 22.8% (13/57) in a period during 30 days and 60 days) and 22.8% (13/57) in a period during 60 days and 180 days). The diagnosed CRT patients had been treated with rivaroxaban 15 mg.bid.po for 3 months. During the 3 months, 100.0% of the thrombosis waned, 71.9% (41/57) of the thrombosis waned within 30 days, 19.3% (11/57) in a period during 30 and 60days and 8.8% (5/57) in a period during 60 days and 90 days. Univariate and multivariate analysis indicated that the risk of CRT in subclavian vein catheterization was higher than that in PICC, respectively ( OR=2.898, 95% CI:1.386-6.056 P=0.005), and the type of catheterization was an independent factor for the formation of thrombosis. Safety analysis result showed that in the prevention of CRT, rivaroxaban treatment did not induce drug-related bleeding, liver function damage, bone marrow suppression or any other side effects. While CRT diagnosed patients were treated with anticoagulation, they kept the central venous catheter, and the infusion was smooth. These patients all finished the anti-tumor treatment as planned, and no abnormalities like new thrombosis or pulmonary embolism were observed. Conclusions:In the mid-term analysis, the proportion of Rivaroxaban in preventing anticoagulant CRT decreases, but it don't reach statistical significance. The sample size should be further increased for observation. Rivaroxaban is proved effective and very safe in the treatment of CRT, and does not affect the concurrent chemotherapy. Medical personnel should carry out the policy of "early prevention, early detection and early treatment" for CRT so as to improve the patients' quality of life.

Objective:To explore the efficacy and safety of Rivaroxaban in preventing catheter related thrombosis (CRT) in patients with breast cancer who are undergoing central venous catheter chemotherapy, and provide basis for making standardized prevention and treatment strategies.Methods:In this research, a prospective cohort study was adopted, and breast cancer patients who received central venous catheter chemotherapy in Sanhuan Cancer Hospital during September 2020 to March 2022 were selected as a treatment group to take the rivaroxaban anticoagulation therapy with 10 mg.po.qd for one month. The control group got no preventive anticoagulation therapy. Vascular ultrasound examination was taken to confirm the occurrence of CRT, and a chi-square test was done for comparison the disparity between the groups. Logistic regression was applied to analyze the univariate and multivariate factors for the formation of CRT.Results:In the research, a total of 235 patients were selected, and there were a total of 19 035 days of catheterization with 81 days of catheterization on average. While in the control group, the incidence of CRT was 28.0% (33/118), the incidence of CRT in the treatment group was 20.5% (24/117), the difference was no significant ( P=0.183). Subgroup analysis results showed that the peripherally inserted central catheter (PICC) was performed in 165 cases with the CRT incidence of 18.2% (30/165) and thrombosis was mostly seen around axillary vein, accounting for 63.3%. Subclavian vein catheterization was performed in 63 cases with the CRT incidence of 39.7% (25/63), and thrombosis was mostly seen around subclavian vein, accounting for 88.0% (22/25). Implantable venous access port was implanted in 7 cases around subclavian vein and internal jugular vein with the CRT incidence of 28.6% (2/7). The patients who developed CRT within 30 days after catheterization accounted for 54.4% (31/57), 22.8% (13/57) in a period during 30 days and 60 days) and 22.8% (13/57) in a period during 60 days and 180 days). The diagnosed CRT patients had been treated with rivaroxaban 15 mg.bid.po for 3 months. During the 3 months, 100.0% of the thrombosis waned, 71.9% (41/57) of the thrombosis waned within 30 days, 19.3% (11/57) in a period during 30 and 60days and 8.8% (5/57) in a period during 60 days and 90 days. Univariate and multivariate analysis indicated that the risk of CRT in subclavian vein catheterization was higher than that in PICC, respectively ( OR=2.898, 95% CI:1.386-6.056 P=0.005), and the type of catheterization was an independent factor for the formation of thrombosis. Safety analysis result showed that in the prevention of CRT, rivaroxaban treatment did not induce drug-related bleeding, liver function damage, bone marrow suppression or any other side effects. While CRT diagnosed patients were treated with anticoagulation, they kept the central venous catheter, and the infusion was smooth. These patients all finished the anti-tumor treatment as planned, and no abnormalities like new thrombosis or pulmonary embolism were observed. Conclusions:In the mid-term analysis, the proportion of Rivaroxaban in preventing anticoagulant CRT decreases, but it don't reach statistical significance. The sample size should be further increased for observation. Rivaroxaban is proved effective and very safe in the treatment of CRT, and does not affect the concurrent chemotherapy. Medical personnel should carry out the policy of "early prevention, early detection and early treatment" for CRT so as to improve the patients' quality of life.

Objective: To explore the relationship between mobile phone dependence (MPD) and academic burden among junior middle school students in Guizhou Province, under the "double reduction" policy by using a multi level model, so as to provide a basis for preventing the occurrence of MPD. Methods: From December 2021 to January 2022, 7 868 students from grade 1 to grade 3 in 3 cities (prefecture) of Guizhou Province were selected by multi stage stratification random sampling method, and on site investigation was conducted by self compiled questionnaire and Self rating Questionnaire for Adolescent Problematic Mobile Phone Use(SQAPMPU). Using MLwiN 2.30 to fit a multi level model of the relationship between MPD and academic burden among junior middle school students. Results: The MPD detection rate of junior middle school students in Guizhou Province was 20.9%. The multi level model revealed that MPD of junior middle school students was clustered at the level of school and class ( χ 2= 1 565.32 , P <0.01), and high perceived academic pressure had a positive predictive effect on MPD among junior middle school students ( β =1.96). Homework duration ≥90 min/d at weekends had a negative predictive effect on MPD ( β =-0.55), while participation in off campus training on learning days had a positive predictive effect ( β =1.66)( P <0.05). Conclusion The MPD occurrence level is higher among junior middle school students in Guizhou Province. Perceived academic pressure, time spent on homework during weekends, off campus training and other academic burdens have an impact on MPD among junior middle school students, which should be a cause of concern for schools, families and social departments.

Objective: To evaluate the clinical effect of clear aligners in the anterior region in non-extraction cases by establishing a three-dimensional model of crown-root fusion to guide clinical application. Methods: Eleven patients visiting the orthodontic department of Xuzhou Stomatological Hospital from December 2020 to December 2021 were collected, and the orthodontic plan was designed using Maestro 3D Dental Studio scheduling software to obtain the expected three-dimensional model of the patient's orthodontic treatment result. CBCT, intraoral scan, and 3D reconstruction software were used to create a postoperative model of the patient. The crown and root data were aligned in Geomagic Studio 2014, and differences in torque and axial inclination between the actual model after treatment and the predicted model of the anterior teeth before treatment were compared in 3-matic. Results: The actual torque angles of the anterior teeth were all smaller than the predicted angles before treatment, with the highest realization rate of 77.55% for lateral incisors and the lowest of 60.70% for central incisors; the actual axial inclination angles of the anterior teeth were also smaller than the predicted angles before treatment, with the highest realization rate of 81.49% for central incisors and the lowest of 74.95% for cuspids. Conclusion A digital model of crown-root integration based on a combination of 3D reconstruction and intraoral scanning techniques is advantageous in assessing the efficacy of clear aligners. In non-extraction cases with clear aligner, the efficiency of movement is higher for small areas of the anterior region.

Objective:To confirm the reuse of mismatched regenerated motor axons of brachial plexus and explore the effect of target organs on their regeneration in a rat model.Methods:This study was carried out between January 2021 and December 2021 at the research laboratory of the Department of Microsurgery, Orthopaedic Trauma and Hand Surgery, the First Affiliated Hospital of Sun Yat-sen University. Animals were randomly assigned into 2 groups, as a regeneration group (RGen) with 5 subgroups and a reuse group (RUs) with 3 subgroups. There were 6 rats per subgroup with 42 rats in total. It was observed that in the groups of RGen1-4, after the transection and suture of the musculocutaneous nerve, the motor axons of the proximal end could accurately grow into the distal corresponding endoneural tube. It was also observed that in the mismatched regenerated group, motor axons were the axons that grew into the endoneurial tube of the lateral forearm cutaneous nerve (LFCN), and other non-target organ contacts were made to the regenerated nerves after mismatch. It was specifically further divided into RGen1, the group without an organ for nerve to make contact with; RGen2, the group with skin as the target organ with nerves contact by neurorrhaphy; RGen3, the group with skin as the target organ with originally reserved natural nerve contact; RGen4, the group with muscle as the target organ with nerves contact by neurorrhaphy and RGen5, a control group. After 8 weeks, the positive area (PA), mean density (MD) and integral optical density (IOD) were measured, with AChE and ChAT fluorescence staining of the medial branch of LFCN, to evaluate the regenerated nerves after mismatch. Of the RUs group, firstly, the innervating branches of the flexor carpi radialis (FCR) were dissected and exposed, then further assigned according to initially innervated FCR (RUs1), contacted with regenerated nerves after mismatch (RUs2) and denervated (RUs3), respectively. After 8 weeks, compound muscle action potential (CMAP) and wet weight ratio of FCR were taken. Masson staining of FCR was also performed to evaluate muscle reinnervation by the regenerated nerves after mismatch. Data analysis with One-Way ANOVA and Bonferroni 0.05 indicated a statistically significant difference.Results:In the RGen groups, after AChE staining, the PA, MD and IOD of RGen3 and RGen4 were higher than that of RGen1 and RGen5, and PA of RGen4 were higher than that of RGen2, with a statistically significant difference ( P<0.05). After ChAT staining, the values of PA and IOD of RGen3 and RGen4 were higher than that of RGen1 and RGen5, and PA of RGen4 were higher than that of RGen2, with a statistically significant difference ( P<0.05). In the RUs, electrophysiological assessment showed that no CMAP was observed in RUs3, there was no significant difference in Latency of RUs1 and RUs2. The difference was statistically significant ( P<0.05). Wet weight rate of muscle of RUs1 (98.91%±3.86%) was higher than that of RUs3 (86.67%±4.68%) with a statistically significant difference ( P<0.01), but no significant difference when compared with RU2 (92.74%±3.88%). Masson staining showed that the CVF value of RUs2 (8.61%±1.16%) was significantly higher than that of RUs1 (3.17%±0.76%), and statistic significantly lower than that of RUs3 (16.44%±2.26%)( P<0.01). Conclusion:Target organ contact can promote the regenerated nerves after mismatched regeneration, and the muscle target organs exhibit greater facilitation than the cutaneous target organs. Besides, regenerated nerves after mismatch can establish effective innervation with muscle target organs, comfirming their effective reuse.

Objective:To investigate the relationship of papillary thyroid microcarcinoma (PTMC) with serum thyroglobulin.Methods:Data of 539 patients with papillary thyroid nodule (≤1cm) in Department of Thyroid and Breast Surgery of the Second Hospital of Anhui Medical University and the Department of Oncology Surgery of Suzhou Municipal Hospital for thyroidectomy were retrospectively analyzed. All of the nodules were classified as TI-RADS 4b with ultrasound. According to the postoperative pathological results, patients were divided into PTMC group (experiment group) and benign tumor group (control group) . The PTMC patients were also divided into lymph node metastasis group (experiment group) and no lymph node metastasis group (control group) based on the cervical lymph node metastasis. Then we analyzed the relationship between thyroid stimulating hormone (TSH) , thyroglobulin antibody (TgAb) , thyroid peroxidase antibody (TPOAb) and thyroglobulin (Tg) with PTMC and lymph node metastasis by SPSS.Results:Age, TSH, Tg and TgAb were independent risk factors for PTMC, B: -0.020, 0.192, 0.026, 0.008, 95% CI: 0.962-0.998, 1.045-1.404, 1.015-1.038, 1.003-1.014, both P<0.05. The relations between PTMC and TSH, Tg and TgAb were positive, while age was in negative correlation with PTMC. Meanwhile, age and thyroglobulin (Tg) were also independent risk factors for lymph node metastasis in PTMC patients, B: -0.025, 0.014, 95% CI: 0.957-0.994, 1.008-1.021, both P<0.05. Age was negatively correlated with lymph node metastasis and Tg was positively correlated with lymph node metastasis. Tg level higher than 26.520 ng/ml indicated that the nodule was PTMC (sensitivity: 0.560, specificity: 0.719) , and Tg level higher than 36.695 ng/ml predicted lymph node metastasis in PTMC patients (sensitivity: 0.532, specificity: 0.788) . Conclusion:Tg is a sensitive serum index for identifying PTMC from benign thyroid nodule, and it is also related to lymph node metastasis in PTMC patients.

Rheumatic mitral valve disease is one of the main causes of mitral valve disease in China,as one of the ideal surgical methods for rheumatic mitral valve disease,mitral valve repair is more complicated than replacement of mitral valve.Although the surgical strategy of mitral valve repair is similar to that of degenerative changes,rheumatic lesions and ischemic mitral valve diseases and our team experience,the degree,characteristics and location of mitral valve rheumatic lesions are significantly different from that of degenerative and ischemic lesions,so the choice of repair strategy is also different.Combined with the characteristics of rheumatic mitral valve diseases,the surgical repair strategies of rheumatic mitral valve diseases are reviewed.

Objective To report a case of Costello syndrome complicated by curis laxa,and to make a molecular genetic diagnosis.Methods Clinical data were collected from a case of Costello syndrome complicated by cutis laxa.Skin tissues were resected from the patient,and peripheral blood samples were obtained from the patient's parents and 150 unrelated healthy controls.Genomic DNA was extracted from these samples,and all the exons and their flanking sequences of the HRAS gene were analyzed by DNA sequencing.Results The 13-month-old female patient presented with growth retardation,severe malnutrition,coarse facial appearance,severely loose skin over the limbs,and decrease or disappearance of subcutaneous fat.A heterozygous mutation c.34G ＞ T (p.Gly12Cys) was detected in exon 2 of the HRAS gene in the patient,but not in her parents or 150 unrelated healthy controls.Conclusion The c.34G ＞ T (p.Gly12Cys) mutation in exon 2 of the HRAS gene may be responsible for Costello syndrome in the patient.

Microglia play a pivotal role in clearance of Aβ by degrading them in lysosomes, countering amyloid plaque pathogenesis in Alzheimer's disease (AD). Recent evidence suggests that lysosomal dysfunction leads to insufficient elimination of toxic protein aggregates. We tested whether enhancing lysosomal function with transcription factor EB (TFEB), an essential regulator modulating lysosomal pathways, would promote Aβ clearance in microglia. Here we show that microglial expression of TFEB facilitates fibrillar Aβ (fAβ) degradation and reduces deposited amyloid plaques, which are further enhanced by deacetylation of TFEB. Using mass spectrometry analysis, we firstly confirmed acetylation as a previously unreported modification of TFEB and found that SIRT1 directly interacted with and deacetylated TFEB at lysine residue 116. Subsequently, SIRT1 overexpression enhanced lysosomal function and fAβ degradation by upregulating transcriptional levels of TFEB downstream targets, which could be inhibited when TFEB was knocked down. Furthermore, overexpression of deacetylated TFEB at K116R mutant in microglia accelerated intracellular fAβ degradation by stimulating lysosomal biogenesis and greatly reduced the deposited amyloid plaques in the brain slices of APP/PS1 transgenic mice. Our findings reveal that deacetylation of TFEB could regulate lysosomal biogenesis and fAβ degradation, making microglial activation of TFEB a possible strategy for attenuating amyloid plaque deposition in AD.
Alzheimer Disease ; metabolism ; pathology ; Amyloid beta-Peptides ; metabolism ; Amyloid beta-Protein Precursor ; genetics ; metabolism ; Animals ; Basic Helix-Loop-Helix Leucine Zipper Transcription Factors ; chemistry ; genetics ; metabolism ; Brain ; metabolism ; Cells, Cultured ; Chloride Channels ; genetics ; metabolism ; Disease Models, Animal ; HEK293 Cells ; Humans ; Lysosomes ; genetics ; metabolism ; Mice ; Mice, Transgenic ; Microglia ; cytology ; metabolism ; Mutagenesis, Site-Directed ; Peptides ; analysis ; chemistry ; Protein Binding ; RNA Interference ; Sirtuin 1 ; antagonists & inhibitors ; genetics ; metabolism