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

Objective:To assess the safety and efficacy of thiotepa, busulfan, and etoposide (TBE) conditioning followed by autologous hematopoietic stem-cell transplantation (TBE auto-HSCT) in primary central nervous system lymphoma (PCNSL) patients.Methods:Clinical data from 27 PCNSL patients who received TBE auto-HSCT at the Fifth Medical Center of PLA General Hospital between November 1, 2021, and April 30, 2024, were retrospectively analyzed.Results:Twenty-seven patients [16 males, 11 females; median age 57 (23–72) years] were included, with 12 (44.4%, 12/27) over 60. Twenty-five had newly diagnosed PCNSL and 2 were relapsed. Median time from diagnosis to transplantation was 6.9 (5.0–10.0) months. TBE auto-HSCT increased complete remission (CR) rate from 63.0 to 96.3% ( P= 0.005), and 9 of 10 patients in partial remission achieving CR post-transplant. Median follow-up was 24.5 months (range 2.0–36.0). Two-year progress-free and OS rates were (87.2±6.9) % and (88.6±6.2) %, respectively. Common grade 3 nonhematologic adverse events were diarrhea (18.5%, 5/27) and bacterial infections (14.8%, 4/27). One patient (64 years old) died from carbapenem-resistant Enterobacteriaceae infection within 2 months post-transplant, yielding a 100-day treatment-related mortality of 3.7% (1/27) . Conclusion:TBE-conditioned high-dose chemotherapy with auto-HSCT is effective, safe, and well-tolerated in PCNSL patients, including the elderly.

Objective:To introduce a new technique of precise exposure and preservation of membranous semicircular canal under endoscope, and to evaluate the protective effect of this method on hearing preservation of semicircular canal occlusion.Methods:The study included three patients with unilateral refractory Meniere′s disease, including 1 male and 2 females, with hearing stage 4 in 2 cases and stage 3 in 1 case, the average hearing thresholds were 72.5, 82.5 and 48.8 dBHL, respectively. All of them were treated with triple semicircular canal occlusion under continuous irrigating mode of endoscopic ear surgery (CIM-EES) in RenMin Hospital of WuHan University. The surgical procedure involved the following key steps: the bony walls of the three semicircular canals near the ampullae were gradually thinned to expose the blue line. The endoscope was positioned as close as possible to the operating area to obtain a clear, magnified view. A micro hook needle was used to create a window on the bony semicircular canals. The hook needle progressively removed the bony material while preserving the membranous canals, which were clearly visible during the procedure. The bone dust was removed out of the surgical area by the continuous exchanged insuline without the help of suction that can avoid the damage of the membranous semicircular canals caused by aspiration and the open bony canals were precisely filled with bone wax and covered with bone powder to ensure complete occlusion of the three semicircular canals. Postoperative follow-up included regular assessments of vertigo control and hearing preservation.Results:All the 3 patients obtained complete hearing preservation at 6 months after surgery, and the hearing preservation rate was 100%. The average hearing thresholds at 6 months postoperatively were 66.3, 81.3, and 50.0 dBHL, respectively. Postoperatively, all patients experienced horizontal spontaneous nystagmus toward the healthy side on the day of surgery and the first day after surgery. One patient reported complete disappearance of tinnitus, while the other two patients showed no change in tinnitus severity. Postoperative MRI revealed complete occlusion of the three semicircular canals with normal vestibular imaging. At 6 months postoperatively, none of the patients experienced any vertigo attacks, suggesting effective control of vertigo symptoms.Conclusions:Precise Semicircular canal occlusion under CIM-EES is a promising technique for the treatment of intractable vertigo in patients with refractory Meniere′s disease. This method provides clear visualization of the membranous canals, reducing the risk of inner ear damage and preserving hearing function of the patients.

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.

Image 1.

Objective To investigate the molecular mechanism of hepatic fibrosis(HF)regulation by liver sinusoidal endothelial cells(LSECs)via endothelial mesenchymal transition(EnMT),and to predict the natural active components using bioinformatics,machine learning,and cellular experiments.Methods HF and EnMT gene matrices were obtained and the intersecting genes were extracted and enriched using Limma difference analysis and weighted gene co-expression network analysis(WGCNA).The diagnostic genes were screened using a combination of random forest method,support vector machine-recursive feature elimination and network topology analysis,and immune infiltration analysis and prediction of natural active ingredients were performed.The expression of diagnostic genes and the pharmacological effects of the predicted ingredients were finally verified by cellular experiments.Results Differential analysis yielded 3034 EnMT-associated and 4133 HF-associated differential genes.WGCNA analysis yielded 4589 EnMT-associated Hub genes and 763 HF-associated Hub genes.Thirty-eight intersecting genes were extracted,which were mainly enriched in the pathways of basement membrane and extracellular matrix receptor interaction.Four diagnostic genes,CFP,COL4A2,ITGA1,and GRPEL1,were screened by multidimensional analysis.Immune infiltration analysis showed that the diagnostic genes were closely associated with mast cell resting state,memory B cells,and memory CD4+T cells.Reverse transcription-polymerase chain reaction analysis showed significantly increased mRNA expression levels of the four diagnostic genes in the Jagged1-induced model group(P＜0.05).The predicted components,sterol,kaempferol,and quercetin,all had good binding activities with the diagnostic genes.Enzyme-linked immunosorbent assay result confirmed that all three active components significantly reduced the expression of collagen type Ⅳ α2 chain protein in Jagged1-induced LSECs,with quercetin having the most significant effect(P＜0.01).Conclusions This study elucidated the molecular mechanism of hepatic sinusoidal endothelial cells involved in the pathological process of HF through mesenchymal transition.We also propose a diagnostic marker system including CFP,COL4A2,ITGA1,and GRPEL1 as core genes.The result also suggest that natural active ingredients,such as quercetin,may exert anti-HF pharmacological effects by targeting these diagnostic genes.