BACKGROUND:Recent research indicates that disc degeneration is closely related to abnormal stress load,and mechanotransduction proteins play a key role in it. OBJECTIVE:To investigate the role and mechanism of mechanotransduction proteins in the mechanotransduction process induced by abnormal mechanical stimulation in disc degeneration,and to summarize the current treatment strategies targeting mechanotransduction to delay intervertebral disc degeneration. METHODS:Using"intervertebral disc,nucleus pulposus,annulus fibrosus,cartilaginous endplate,cell,mechanics,signal transduction,protein,biomechanics"as Chinese search terms,and"intervertebral disc,nucleus pulposus,annulus fibrosus,cartilaginous endplate,cell,mechanical stimulation,signal transduction,protein,biomechanics"as English search terms,relevant literature in the PubMed and CNKI databases was searched.A total of 88 articles were ultimately included for review. RESULTS AND CONCLUSION:Disc cells can sense external mechanical stimulation through various mechanotransduction proteins and convert it into biological responses within the cells.These transduction proteins mainly include collagen proteins in the extracellular matrix,cell membrane surface receptors(such as integrins and ion channels),and cytoskeleton structural proteins.Their regulation of mechanotransduction processes primarily involves the activation of multiple pathways,such as the PI3K/AKT signaling pathway,nuclear factor-kB signaling pathway,and Ca2+/Calpain2/Caspase3 pathway.Mechanotransduction proteins play a key role in the mechanotransduction of disc cells.Abnormal expression of these proteins or resulting changes in the extracellular matrix environment can disrupt the mechanical balance of disc cells,leading to disc degeneration.In-depth study of the expression and regulatory mechanisms of mechanotransduction proteins in disc cells,and identification of key pathological links and therapeutic targets,is of significant importance for developing treatment strategies for disc degeneration.Current strategies to delay intervertebral disc degeneration by targeting mechanotransduction mainly include regulation of transduction proteins and improvement of the extracellular matrix.However,research in this area is still in its early stages.As research continues,new breakthroughs are expected in the regulation of disc degeneration by mechanotransduction proteins.

Background: The genetic basis for hyperglycaemia in pregnancy remain unclear. This study aimed to uncover the genetic determinants of gestational diabetes mellitus (GDM) and investigate their applications. Methods: We performed a meta-analysis of genome-wide association studies (GWAS) for GDM in Chinese women (464 cases and 1,217 controls), followed by de novo replications in an independent Chinese cohort (564 cases and 572 controls) and in silico replication in European (12,332 cases and 131,109 controls) and multi-ethnic populations (5,485 cases and 347,856 controls). A polygenic risk score (PRS) was derived based on the identified variants. Results: Using the genome-wide scan and candidate gene approaches, we identified four susceptibility loci for GDM. These included three previously reported loci for GDM and type 2 diabetes mellitus (T2DM) at MTNR1B (rs7945617, odds ratio [OR], 1.64; 95% confidence interval [CI],1.38 to 1.96]), CDKAL1 (rs7754840, OR, 1.33; 95% CI, 1.13 to 1.58), and INS-IGF2-KCNQ1 (rs2237897, OR, 1.48; 95% CI, 1.23 to 1.79), as well as a novel genome-wide significant locus near TBR1-SLC4A10 (rs117781972, OR, 2.05; 95% CI, 1.61 to 2.62; Pmeta=7.6×10-9), which has not been previously reported in GWAS for T2DM or glycaemic traits. Moreover, we found that women with a high PRS (top quintile) had over threefold (95% CI, 2.30 to 4.09; Pmeta=3.1×10-14) and 71% (95% CI, 1.08 to 2.71; P=0.0220) higher risk for GDM and abnormal glucose tolerance post-pregnancy, respectively, compared to other individuals. Conclusion Our results indicate that the genetic architecture of glucose metabolism exhibits both similarities and differences between the pregnant and non-pregnant states. Integrating genetic information can facilitate identification of pregnant women at a higher risk of developing GDM or later diabetes.

Background: The genetic basis for hyperglycaemia in pregnancy remain unclear. This study aimed to uncover the genetic determinants of gestational diabetes mellitus (GDM) and investigate their applications. Methods: We performed a meta-analysis of genome-wide association studies (GWAS) for GDM in Chinese women (464 cases and 1,217 controls), followed by de novo replications in an independent Chinese cohort (564 cases and 572 controls) and in silico replication in European (12,332 cases and 131,109 controls) and multi-ethnic populations (5,485 cases and 347,856 controls). A polygenic risk score (PRS) was derived based on the identified variants. Results: Using the genome-wide scan and candidate gene approaches, we identified four susceptibility loci for GDM. These included three previously reported loci for GDM and type 2 diabetes mellitus (T2DM) at MTNR1B (rs7945617, odds ratio [OR], 1.64; 95% confidence interval [CI],1.38 to 1.96]), CDKAL1 (rs7754840, OR, 1.33; 95% CI, 1.13 to 1.58), and INS-IGF2-KCNQ1 (rs2237897, OR, 1.48; 95% CI, 1.23 to 1.79), as well as a novel genome-wide significant locus near TBR1-SLC4A10 (rs117781972, OR, 2.05; 95% CI, 1.61 to 2.62; Pmeta=7.6×10-9), which has not been previously reported in GWAS for T2DM or glycaemic traits. Moreover, we found that women with a high PRS (top quintile) had over threefold (95% CI, 2.30 to 4.09; Pmeta=3.1×10-14) and 71% (95% CI, 1.08 to 2.71; P=0.0220) higher risk for GDM and abnormal glucose tolerance post-pregnancy, respectively, compared to other individuals. Conclusion Our results indicate that the genetic architecture of glucose metabolism exhibits both similarities and differences between the pregnant and non-pregnant states. Integrating genetic information can facilitate identification of pregnant women at a higher risk of developing GDM or later diabetes.

Background: The genetic basis for hyperglycaemia in pregnancy remain unclear. This study aimed to uncover the genetic determinants of gestational diabetes mellitus (GDM) and investigate their applications. Methods: We performed a meta-analysis of genome-wide association studies (GWAS) for GDM in Chinese women (464 cases and 1,217 controls), followed by de novo replications in an independent Chinese cohort (564 cases and 572 controls) and in silico replication in European (12,332 cases and 131,109 controls) and multi-ethnic populations (5,485 cases and 347,856 controls). A polygenic risk score (PRS) was derived based on the identified variants. Results: Using the genome-wide scan and candidate gene approaches, we identified four susceptibility loci for GDM. These included three previously reported loci for GDM and type 2 diabetes mellitus (T2DM) at MTNR1B (rs7945617, odds ratio [OR], 1.64; 95% confidence interval [CI],1.38 to 1.96]), CDKAL1 (rs7754840, OR, 1.33; 95% CI, 1.13 to 1.58), and INS-IGF2-KCNQ1 (rs2237897, OR, 1.48; 95% CI, 1.23 to 1.79), as well as a novel genome-wide significant locus near TBR1-SLC4A10 (rs117781972, OR, 2.05; 95% CI, 1.61 to 2.62; Pmeta=7.6×10-9), which has not been previously reported in GWAS for T2DM or glycaemic traits. Moreover, we found that women with a high PRS (top quintile) had over threefold (95% CI, 2.30 to 4.09; Pmeta=3.1×10-14) and 71% (95% CI, 1.08 to 2.71; P=0.0220) higher risk for GDM and abnormal glucose tolerance post-pregnancy, respectively, compared to other individuals. Conclusion Our results indicate that the genetic architecture of glucose metabolism exhibits both similarities and differences between the pregnant and non-pregnant states. Integrating genetic information can facilitate identification of pregnant women at a higher risk of developing GDM or later diabetes.

Background: The genetic basis for hyperglycaemia in pregnancy remain unclear. This study aimed to uncover the genetic determinants of gestational diabetes mellitus (GDM) and investigate their applications. Methods: We performed a meta-analysis of genome-wide association studies (GWAS) for GDM in Chinese women (464 cases and 1,217 controls), followed by de novo replications in an independent Chinese cohort (564 cases and 572 controls) and in silico replication in European (12,332 cases and 131,109 controls) and multi-ethnic populations (5,485 cases and 347,856 controls). A polygenic risk score (PRS) was derived based on the identified variants. Results: Using the genome-wide scan and candidate gene approaches, we identified four susceptibility loci for GDM. These included three previously reported loci for GDM and type 2 diabetes mellitus (T2DM) at MTNR1B (rs7945617, odds ratio [OR], 1.64; 95% confidence interval [CI],1.38 to 1.96]), CDKAL1 (rs7754840, OR, 1.33; 95% CI, 1.13 to 1.58), and INS-IGF2-KCNQ1 (rs2237897, OR, 1.48; 95% CI, 1.23 to 1.79), as well as a novel genome-wide significant locus near TBR1-SLC4A10 (rs117781972, OR, 2.05; 95% CI, 1.61 to 2.62; Pmeta=7.6×10-9), which has not been previously reported in GWAS for T2DM or glycaemic traits. Moreover, we found that women with a high PRS (top quintile) had over threefold (95% CI, 2.30 to 4.09; Pmeta=3.1×10-14) and 71% (95% CI, 1.08 to 2.71; P=0.0220) higher risk for GDM and abnormal glucose tolerance post-pregnancy, respectively, compared to other individuals. Conclusion Our results indicate that the genetic architecture of glucose metabolism exhibits both similarities and differences between the pregnant and non-pregnant states. Integrating genetic information can facilitate identification of pregnant women at a higher risk of developing GDM or later diabetes.

Objective:To introduce a new design of super-micro flap for endoscopic ear surgery, and to evaluate the application effect of super-micro flap in endoscopic tympanoplasty. Methods:Between January, 2023 and March, 2024, 58 patients（64 ears） with tympanosclerosis underwent tympanoplasty with super-micro flap. Continuous irrigating mode endoscopic ear surgery（CIM-EES） was used to complete type Ⅱ or Ⅲ tympanoplasty with the tragus cartilage with followed up for 12 to 24 months. The operation time, postoperative efficacy and complications were statistically analyzed. Results:Of the 64 ears, 63 ears had primary healing of the tympanic membrane, and 1 ear had cartilage necrosis due to multi-drug resistant bacteria infection. The second operation was performed one year later, and the success rate of operation was 98.40%. The average operation time was （48.40±8.86） minutes. The average hearing threshold of 0.5 kHz to 4.0 kHz before operation was （59.63±10.62） dB HL, and the average air conduction threshold of 0.5 kHz to 4.0 kHz one year after operation was（38.79±10.91） dB HL, which was significantly improved compared with that before operation（P<0.01）. Bone conduction threshold also improved significantly （24.49±8.55） dB HL vs（21.88±7.58） dB HL（P<0.01）. No outer tympanic membrane healing and ear canal scar stenosis occurred. Conclusion:The design of super-micro flap can effectively solve the interference of flap floating during continuous irrigating mode in endoscopic ear surgery, relieve the difficulty of flap reposition, simplify the operation process, help to shorten the operation time, and reduce the possibility of circular scar stenosis of conventional free flap, which provides a new flap design option for endoscopic ear surgery.
Humans ; Tympanoplasty/methods* ; Endoscopy/methods* ; Surgical Flaps ; Male ; Female ; Adult ; Myringosclerosis/surgery* ; Middle Aged ; Treatment Outcome ; Tympanic Membrane/surgery* ; Adolescent ; Young Adult

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Objective:To explore the effect of psychodrama therapy in adolescent inpatients with mental disor-ders.Methods:Totally 22 patients with mental disorders(aged 12-18 years)were recruited from the inpatient children's ward of a certain hospital.According to the interview outline,a semi-structured interview was conducted in adolescent inpatients with mental disorders who participated in 4 sessions of psychodrama therapy.These patients took psychotropic drugs regularly.The interview data were analyzed in depth by using the grounded theory meth-od.The self-compiled Psychodrama Therapy Participation Feeling and Evaluation Questionnaire was used to investi-gate the feelings,gains or changes of patients after psychodrama therapy.Results:The interview analysis found that the effects of psychodrama therapy included reducing symptoms,improving self-esteem,promoting functional recov-ery and improving social adaptability.The results of the self-compiled Psychodrama Therapy Participation Feeling and Evaluation Questionnaire showed that the top 4 aspects were promoting interpersonal relationship,being inter-esting,willing to continue to participate and improving self-confidence.Conclusion:Psychodrama therapy has an auxiliary therapeutic effect in adolescent inpatients with mental disorders,and can promote the improvement of self-esteem and social skills.

Objective To establish the UPLC fingerprint chromatogram combined with chemometric analysis for the quality evaluation of classical formula Linggui Zhugan Decoction.Methods SHIMADZU Shim-Pack GIST C18 column(100 mm×2.1 mm,2.0 μm)was used with acetonitrile-0.1%phosphoric acid aqueous solution as mobile phase,gradient elution;flow rate was 0.2 mL/min;the detection wavelength was 266 nm for the first 30 minutes and 235 nm for the last 36 minutes;the column temperature was 30℃.The UPLC fingerprint of Linggui Zhugan Decoction was established by Similarity Evaluation System for Chromatographic Fingerprint of TCM(2012.130723 version),and the common peak was determined and the similarity evaluation was carried out.Based on the peak area determination results of the common peak of the fingerprint,the quality of different batches of Linggui Zhugan Decoction was evaluated by chemometrics such as clustering analysis and principal component analysis.Results A total of 24 common peaks were confirmed and 14 components were identified by using reference substances.The similarity of 10 batches of Linggui Zhugan Decoction samples was greater than 0.950,which could be divided into two categories by chemometrics,and the principal component 1-4 were the main factors affecting its quality evaluation.OPLS-DA identified 6 differential markers.Conclusion The fingerprint research method established in the study is simple,reliable and reproducible.Through the method of fingerprint combined with chemometrics analysis,the differences between Linggui Zhugan Decoction from different origins of medicinal materials are identified,which provides a reference for the internal quality evaluation of Linggui Zhugan Decoction.

Objective To explore the effect of endoplasmic reticulum stress activating transcription factor 6(ATF6)on the expression of reproduction related gene heat shock protein family A member 1 like(HSPA1L)and preliminari-ly clarify its regulatory molecular mechanism.Methods The ATF6 over-expression plasmid was transfected into HEK-293T cells and the over-expression efficiency was verified by RT-qPCR and Western blot.The transcriptome sequen-cing information of testis tissue of male ATF6 knockout mice was used to screen five reproduction related genes down-stream of ATF6.The dual luciferase reporter assay selected the downstream genes with high promoter activity and de-tected the effect of over-expression of ATF6 on the promoter activity of downstream genes.The possible binding sites of ATF6 and downstream gene promoters were predicted by gene-regulation.RT-qPCR and Western blot were used to detect the effect of over-expression of ATF6 on downstream gene expression in HEK-293T cells.Whether ATF6 binds to downstream gene promoters was determined by electrophoretic mobility shift assay(EMSA).Results The expres-sion of ATF6 mRNA(P＜0.001)and protein(P＜0.001 and P＜0.05)in HEK-293T cells was significantly increased after transfection.HSPA1L(P＜0.001 and P＜0.05),a reproductive related gene downstream of ATF6 was screened by transcriptome sequencing and dual luciferase reporter assay.ATF6 promoted the truncated promoter activity of HSPA1L(P＜0.001).After over-expression of ATF6,the expression of HSPA1L was significantly increased(P＜0.001).The differences were statistically significant.ATF6 protein could bind to the aagtcgtcac DNA sequence of HSPA1L promoter.Conclusions ATF6,a key molecule of endoplasmic reticulum stress,regulates the expression of reproduction related gene HSPA1L by binding to the promoter of HSPA1L.This result will lay a foundation for further research on the prevention or treatment of endoplasmic reticulum stress(ERS)related male infertility.