Cardiac troponin I (cTnI), a widely used biomarker for assessing cardiovascular risk, can provide a window for the evaluation of drug-induced myocardial injury. Label-free biosensors are promising candidates for detecting cell secretomes, since they do not require labor-intensive processes. In this work, a label-free electrochemical aptasensor is developed for in situ monitoring of cardiac cell secretomes in cell culture media based on target-induced strand displacement. The aptasensing system contains an aptamer-functionalized signal nanoprobe facing trimetallic metal-organic framework nanosheets and a gold nanoparticle-based detection working electrode modified with DNA nanotetrahedron-based complementary DNA for indirect target detection. The signal nanoprobes (termed CAHA) consisted of copper-based metal-organic frameworks, AuPt nanoparticles, horseradish peroxidase, and an aptamer. When the aptasensor is exposed to cardiac cell secretomes, cTnI competitively binds to the aptamer, resulting in the release of signal nanoprobes from the biorecognition interface and electrochemical signal changes. The aptasensor exhibited rapid response times, a low detection limit of 0.31 pg/mL, and a wide linear range of 0.001-100 ng/mL. We successfully used this aptasensor to measure cTnI concentrations among secreted cardiac markers during antitumor drug treatment. In general, aptasensors can be used to monitor a variety of cardiac biomarkers in the evaluation of cardiotoxicity.

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

Objectives:To investigate the pedicle screw placement accuracy of robot-assisted minimally inva-sive transforaminal lumbar interbody fusion(RA-MIS-TLIF)and analyze its learning curve.Methods:A retro-spective analysis was conducted on the clinical data of 160 patients with degenerative lumbar diseases treated at the Department of Orthopedics,Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hos-pital between January 2019 and June 2022.The patients were divided into a robot group(n=80)and a manual group(n=80)based on the surgical approach.Each group was further divided into four subgroups(1,2,3,4)of 20 patients each,arranged sequentially according to the order of surgery dates.The total operative time,blood loss,and planning and screw placement time of the two surgical methods were statistically analyzed.Preoper-ative,postoperative 1d,and six-month postoperative visual analogue scale(VAS)scores for pain and Oswestry disability index(ODI)were compared across the four subgroups.The trends in total operative time and blood loss with increasing surgery cases were analyzed using a logarithmic regression model.Screw placement clas-sification was evaluated using the Gertzbein-Robbins classification based on postoperative CT scans,and then the screw placement accuracy was calculated.Results:All the surgeries were successfully completed.In the robot group,the total operative time was 162.9±5.7min,blood loss was 91.4±9.5mL,and planning and screw placement time was 42.1±1.3min;In the manual group,the total operative time was 169.1±6.6min,blood loss was 101.0±9.2mL,and planning and screw placement time was 57.0±6.3min.A total of 320 screws were placed in each group,with accuracy rates of 97％(311/320)in the robot group and 92％(295/320)in the manual group.Neither group had grade C or D screws.The total operative time decreased with the increase in the number of surgeries in both groups.The robot group achieved relative stability between subgroups 2 and 3[y=-5.894×ln(x)+183.891,R2=0.576,P＜0.05],while the manual group achieved relative stability between subgroups 3 and 4[y=-4.424×ln(x)+184.221,R2=0.376,P＜0.05].The blood loss also decreased with the increase in the number of surgeries in both groups,the robot group achieved relative stability between subgroups 2 and 3[y=-9.480×ln(x)+125.361,R2=0.547,P＜0.05],and the manual group achieved relative stability also between subgroups 2 and 3[y=-3.868×ln(x)+114.183,R2=0.148,P＜0.05].Postoperative VAS scores in the robot group decreased from 6.9±1.1 preoperatively to 2.4±0.9 on postoperative 1d(P＜0.05)and to 1.1±0.4 at six months(P＜0.05).In the manual group,VAS scores decreased from 7.0±0.9 preoperatively to 2.4±0.9 on postoperative 1d(P＜0.05)and to 1.4±0.6 at six months(P＜0.05).ODI in the robot group decreased from(59.5±7.1)％preoperatively to(20.0±4.1)％on postoperative 1d(P＜0.05)and to(10.8±3.0)％at six months(P＜0.05).In the manual group,ODI scores decreased from(57.7±6.9)％preoperatively to(19.6±4.6)％on postoperative 1d(P＜0.05)and to(11.3±3.4)％at six months(P＜0.05).All the 160 patients completed follow-ups with no severe complications reported during the follow-up period.Conclusions:Comparing with traditional MIS-TLIF with manual pedicle screw placement,RA-MIS-TLIF has a higher accuracy of screw placement and a smoother learning curve,which stabilizes after approximately 20 cases.

Objectives:To investigate the pedicle screw placement accuracy of robot-assisted minimally inva-sive transforaminal lumbar interbody fusion(RA-MIS-TLIF)and analyze its learning curve.Methods:A retro-spective analysis was conducted on the clinical data of 160 patients with degenerative lumbar diseases treated at the Department of Orthopedics,Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hos-pital between January 2019 and June 2022.The patients were divided into a robot group(n=80)and a manual group(n=80)based on the surgical approach.Each group was further divided into four subgroups(1,2,3,4)of 20 patients each,arranged sequentially according to the order of surgery dates.The total operative time,blood loss,and planning and screw placement time of the two surgical methods were statistically analyzed.Preoper-ative,postoperative 1d,and six-month postoperative visual analogue scale(VAS)scores for pain and Oswestry disability index(ODI)were compared across the four subgroups.The trends in total operative time and blood loss with increasing surgery cases were analyzed using a logarithmic regression model.Screw placement clas-sification was evaluated using the Gertzbein-Robbins classification based on postoperative CT scans,and then the screw placement accuracy was calculated.Results:All the surgeries were successfully completed.In the robot group,the total operative time was 162.9±5.7min,blood loss was 91.4±9.5mL,and planning and screw placement time was 42.1±1.3min;In the manual group,the total operative time was 169.1±6.6min,blood loss was 101.0±9.2mL,and planning and screw placement time was 57.0±6.3min.A total of 320 screws were placed in each group,with accuracy rates of 97％(311/320)in the robot group and 92％(295/320)in the manual group.Neither group had grade C or D screws.The total operative time decreased with the increase in the number of surgeries in both groups.The robot group achieved relative stability between subgroups 2 and 3[y=-5.894×ln(x)+183.891,R2=0.576,P＜0.05],while the manual group achieved relative stability between subgroups 3 and 4[y=-4.424×ln(x)+184.221,R2=0.376,P＜0.05].The blood loss also decreased with the increase in the number of surgeries in both groups,the robot group achieved relative stability between subgroups 2 and 3[y=-9.480×ln(x)+125.361,R2=0.547,P＜0.05],and the manual group achieved relative stability also between subgroups 2 and 3[y=-3.868×ln(x)+114.183,R2=0.148,P＜0.05].Postoperative VAS scores in the robot group decreased from 6.9±1.1 preoperatively to 2.4±0.9 on postoperative 1d(P＜0.05)and to 1.1±0.4 at six months(P＜0.05).In the manual group,VAS scores decreased from 7.0±0.9 preoperatively to 2.4±0.9 on postoperative 1d(P＜0.05)and to 1.4±0.6 at six months(P＜0.05).ODI in the robot group decreased from(59.5±7.1)％preoperatively to(20.0±4.1)％on postoperative 1d(P＜0.05)and to(10.8±3.0)％at six months(P＜0.05).In the manual group,ODI scores decreased from(57.7±6.9)％preoperatively to(19.6±4.6)％on postoperative 1d(P＜0.05)and to(11.3±3.4)％at six months(P＜0.05).All the 160 patients completed follow-ups with no severe complications reported during the follow-up period.Conclusions:Comparing with traditional MIS-TLIF with manual pedicle screw placement,RA-MIS-TLIF has a higher accuracy of screw placement and a smoother learning curve,which stabilizes after approximately 20 cases.

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.

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.

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.

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.

Objective To investigate the feasibility of constructing an animal model for training of otoscopic anatomy and surgical operation using living guinea pigs.Methods Eight healthy adult guinea pigs were used as ex-perimental animals to construct a model of endoscopic operation by opening the upper tympanic cavity and abrading the upper wall of the external acoustic meatus to establish a space for endoscopic observation and operation.The an-atomical opening of the temporal bone and basic surgical steps were performed by the same resident on eight guinea pigs.The resident assessed the difficulty and completion of the endoscopic operation and measured various dimen-sions,including the anteroposterior and superior/inferior diameters of the mastoid process,the posterolateral wall of the upper tympanic cavity,and the upper wall of the external acoustic meatus,as well as the maximal depth of entry of the endoscope.Results The fine structures of guinea pig tympanic chamber were clearly displayed under otoen-doscopy.Except for the two steps of free preservation of the chorda tympani nerve and exposure of the stapes after removal of the ossicles,the other steps,such as separation of the tympanic membrane from the malleus,exposure of the malleus-anvil complex,removal of the cochlea shell to observe the cochlea axis,and exposure of the tympanic segment of the facial nerve under the endoscope,were all easily accomplished.The anterior and posterior diameters of the mastoid after opening were 3.56±0.21 and 3.89±0.16 mm,respectively,and the anterior and posterior di-ameters of the upper tympanic cavity and the upper wall of the external acoustic meatus after opening were 5.60±0.09 and 6.02±0.10 mm,respectively.The maximum depth of entry of the otoscopic endoscope was 15.14±0.24 mm.Conclusion Using guinea pig as an animal model for otoscopic surgery training can provide a more realis-tic surgical experience,which is helpful for beginners to be trained in the basic surgical skills of otoscopic surgery and otoscopic anatomy.

BACKGROUND:Minimally invasive surgery is developing rapidly.Robot-assisted minimally invasive transforaminal lumbar interbody fusion and robot-assisted unilateral biportal endoscopic transforaminal/posterior lumbar interbody fusion are important posterior minimally invasive surgical approaches to treat lumbar degenerative diseases.However,it is worth discussing which operation method is more advantageous. OBJECTIVE:To compare the clinical efficacy and imaging examination between different operation groups,and discuss the clinical application value of robot-assisted minimally invasive lumbar posterior fusion technology to treat lumbar degenerative diseases. METHODS:Clinical data of 83 patients with lumbar degenerative diseases from January 2018 to June 2022 at the Department of Orthopedics,Sichuan Academy of Medical Sciences&Sichuan Provincial People's Hospital were retrospectively analyzed.Of them,27 patients received robot-assisted minimally invasive transforaminal lumbar interbody fusion treatment(group A);30 patients received robot-assisted unilateral biportal endoscopic transforaminal/posterior lumbar interbody fusion treatment(group B),and 26 traditional minimally invasive transforaminal lumbar interbody fusion patients were selected as the control group(group C).There were no significant differences in gender,age,body mass index,surgical segment,preoperative visual analog scale score and Oswestry Disability Index among the three groups(P＞0.05).The operation time,intraoperative blood loss,complications,fluoroscopic dose,fluoroscopic time,and fluoroscopic frequency were compared among the three groups.Gertzbein-Robbins'classification was used to evaluate the accuracy of percutaneous pedicle screw.Visual analog scale and Oswestry Disability Index scores were evaluated after surgery.The excellent and good rate of the three surgical options was evaluated using Macnab's criteria. RESULTS AND CONCLUSION:(1)The operation time of group A was significantly shorter than that of groups B and C(P＜0.05),but there was no significant difference between group B and group C(P＞0.05).The intraoperative blood loss in group B was significantly less than that in group A,and that in group A was significantly less than that in group C(P＜0.05).(2)The fluoroscopic dose,fluoroscopic time,and fluoroscopic frequency of group C were significantly higher than those of groups A and B(P＜0.05).(3)Visual analog scale score and Oswestry Disability Index in the three groups significantly improved after operation when compared with that before operation(P＜0.05),but there was no significant difference among the three groups 1 day and 6 months after surgery(P＞0.05).(4)Postoperative imaging showed that the accuracy of percutaneous pedicle screw placement in groups A and B was better than that in group C(P＜0.05).(5)There was no significant difference in the excellent and good rate of MacNab criteria among the three groups(P＞0.05).(6)There was no significant difference in complications among the three groups(P＞0.05).(7)The results indicated that robot-assisted minimally invasive transforaminal lumbar interbody fusion and robot-assisted unilateral biportal endoscopic transforaminal/posterior lumbar interbody fusion are effective surgery methods for lumbar degenerative diseases.Compared with traditional minimally invasive transforaminal lumbar interbody fusion,robot-assisted minimally invasive transforaminal lumbar interbody fusion surgery has higher efficiency,less intraoperative radiation and higher internal fixation accuracy,which has a good clinical application value.