Tracheoesophageal fistula (TEF) is a disease characterized by an abnormal connection between the trachea and esophagus. Benign TEF often results from tracheal intubation injury, typically presenting as coughing exacerbated by swallowing, and can be potentially life-threatening. However, no unified surgical standard currently exists for TEF. The choice of surgical method mainly depends on the location and size of the fistula, as well as the condition of the surrounding tracheal tissue. For small-to-moderate fistulas, tracheal segmental resection with reconstruction is a classic approach. For large, complex, and refractory TEFs, musculocutaneous flap repair is considered an ideal option. This article reviews the application of several common musculocutaneous flaps—including the sternocleidomastoid, pectoralis major, and latissimus dorsi—in the repair of benign TEFs, with the aim of providing a clinical reference.

OBJECTIVES: To reprogram human placental fibroblasts (HPFs) into chemically induced epithelioid-like cells (ciEP-Ls) using a combination of small-molecule compounds. METHODS: HPFs cultured under normoxic conditions were identified using immunofluorescence assay, PCR and chromosomal karyotyping. Under hypoxic conditions (37 ℃, 5% O₂), HPFs were cultured in a medium containing small-molecule compounds C6TSEDRVAJZ (CHIR99021, 616452, TTNPB, SAG, EPZ5676, DZNep, Ruxolitinib, VTP50469, Afuresertib, JNK-IN-8, and EZM0414), and the cell morphology was observed daily. The expression levels of epithelial cell markers in the induced cells were detected by immunofluorescence, Western blotting and PCR. Chromosomal karyotyping of the induced cells was performed and the induction efficiency was calculated. RESULTS: Before induction, HPFs showed positive expressions of fibroblast surface markers CD34 and vimentin and were negative for epithelial surface markers. PCR results showed high expressions of fibroblast-specific genes S100A4 and COL1A1 in HPFs with a normal human diploid karyotype. After one day of induction, the HPFs underwent morphological changes from a multinodular spindle shape to a round or polygonal shape, which was morphologically characteristic of ciEP-Ls. On day 4 of induction, the cells exhibited high expressions of the epithelial cell markers E-cadherin and Lin28A. RT-qPCR results also showed that the cells expressed the epithelial markers Smad3, GLi3, PAX8, WT1, KRT19, and KRT18 with significantly down-regulated expressions of all the fibroblast surface markers and a normal human diploid karyotype. The reprogramming efficiency of HPFs into ciEP-Ls ranged from (64.53±2.8)% to (68.10±3.6)%. CONCLUSIONS The small-molecule compound combination C6TSEDRVAJZ is capable of inducing HPFs into ciEP-Ls under hypoxic conditions with a high induction efficiency.
Humans ; Fibroblasts/drug effects* ; Pregnancy ; Female ; Cell Differentiation/drug effects* ; Pyrimidines/pharmacology* ; Placenta/cytology* ; Cells, Cultured ; Pyridines/pharmacology* ; Pyrazoles/pharmacology* ; Epithelial Cells/cytology*

BACKGROUND:It has been found that anterior knee pain is related to the biomechanics of the lower limbs,but there is still a lack of research on the effects of gluteal muscle training on the knee joint and daily activities of the lower limbs.OBJECTIVE:To investigate the effects of gluteal muscle activation exercise therapy on the muscle strength of hip and knee joint muscle groups and pain in young male patients with anterior knee pain.METHODS:Twenty-five young male patients with anterior knee pain were enrolled and randomly divided into two groups:gluteal muscle activation group(n=12)and blank control group(n=13).The gluteal muscle activation group performed gluteal muscle activation exercises,40 minutes each,3 times/week,for 6 weeks.The blank control group did not perform any intervention.Assessments were conducted at the time of enrollment and again after 6 weeks.The relative peak torque,total work,ratio of flexors and extensors,and muscle endurance values of the affected hip and knee joints were evaluated through isokinetic flexion and extension tests at 60(°)/s and 180(°)/s.At the same time,floors at which climbing was stopped in the stair-climbing test were detected and the visual analog scale score was assessed.RESULTS AND CONCLUSION:(1)Isokinetic knee extension and flexion test:For the hip joint,the gluteal muscle activation group showed a significant increase in the relative peak torque at 60(°)/s and 180(°)/s by 29.74%and 25.95%respectively after intervention(P=0.022,P=0.024);the blank control group showed a 12.12%decrease in muscle endurance at 180(°)/s compared to before intervention(P=0.000).For the knee joints,the gluteal muscle activation group had a significant increase in the relative peak torque at 60(°)/s and 180(°)/s by 18.69%and 7.27%respectively after intervention(P=0.006,P=0.033);there were no significant changes in the blank control group before and after intervention(P>0.05).(2)Stair-climbing test:The number of floors climbed to cessation in the gluteal muscle activation group was(6.41±6.1)floors,which was higher than that in the blank control group(P=0.024),and increased by 33.11%compared with before intervention(P=0.016);there were no significant changes in all the indicators of the blank control group before and after intervention(P>0.05).(3)Pain assessment:After intervention,the visual analogue scale score of the gluteal muscle activation group was significantly lower than that of the blank control(P=0.036),and also decreased compared to before intervention(P=0.000);there were no significant changes in the blank control group before and after intervention(P>0.05).To conclude,the 6-week gluteal activation exercise therapy can improve the explosive power and endurance of the lower limb muscles,and reduce the degree of anterior knee pain.For patients with anterior knee pain,gluteal muscle training is necessary to promote recovery.

BACKGROUND:It has been found that anterior knee pain is related to the biomechanics of the lower limbs,but there is still a lack of research on the effects of gluteal muscle training on the knee joint and daily activities of the lower limbs.OBJECTIVE:To investigate the effects of gluteal muscle activation exercise therapy on the muscle strength of hip and knee joint muscle groups and pain in young male patients with anterior knee pain.METHODS:Twenty-five young male patients with anterior knee pain were enrolled and randomly divided into two groups:gluteal muscle activation group(n=12)and blank control group(n=13).The gluteal muscle activation group performed gluteal muscle activation exercises,40 minutes each,3 times/week,for 6 weeks.The blank control group did not perform any intervention.Assessments were conducted at the time of enrollment and again after 6 weeks.The relative peak torque,total work,ratio of flexors and extensors,and muscle endurance values of the affected hip and knee joints were evaluated through isokinetic flexion and extension tests at 60(°)/s and 180(°)/s.At the same time,floors at which climbing was stopped in the stair-climbing test were detected and the visual analog scale score was assessed.RESULTS AND CONCLUSION:(1)Isokinetic knee extension and flexion test:For the hip joint,the gluteal muscle activation group showed a significant increase in the relative peak torque at 60(°)/s and 180(°)/s by 29.74%and 25.95%respectively after intervention(P=0.022,P=0.024);the blank control group showed a 12.12%decrease in muscle endurance at 180(°)/s compared to before intervention(P=0.000).For the knee joints,the gluteal muscle activation group had a significant increase in the relative peak torque at 60(°)/s and 180(°)/s by 18.69%and 7.27%respectively after intervention(P=0.006,P=0.033);there were no significant changes in the blank control group before and after intervention(P>0.05).(2)Stair-climbing test:The number of floors climbed to cessation in the gluteal muscle activation group was(6.41±6.1)floors,which was higher than that in the blank control group(P=0.024),and increased by 33.11%compared with before intervention(P=0.016);there were no significant changes in all the indicators of the blank control group before and after intervention(P>0.05).(3)Pain assessment:After intervention,the visual analogue scale score of the gluteal muscle activation group was significantly lower than that of the blank control(P=0.036),and also decreased compared to before intervention(P=0.000);there were no significant changes in the blank control group before and after intervention(P>0.05).To conclude,the 6-week gluteal activation exercise therapy can improve the explosive power and endurance of the lower limb muscles,and reduce the degree of anterior knee pain.For patients with anterior knee pain,gluteal muscle training is necessary to promote recovery.

ObjectiveRecent successful restoration of the native conformation and function of the complementary-determining regions (CDRs) of antibodies on gold nanoparticles (AuNPs) demonstrates that the era of molecular conformational engineering is dawning. Basically, molecular conformational engineering aims to precisely tune flexible non-functional molecules into special conformations to carry out novel functions, in the same way as protein folding. In order to explore the general applicability of molecular conformational engineering, as well as to reveal the mechanism of protein structure-function relationship, the objective of this work is to restore the native conformation and function of the CDRs of an antibody on platinum nanoparticles (PtNPs). MethodsThe CDR fragment of the anti-lysozyme antibody cAB-lys3, which has no stable conformation or function in free state, was conjugated onto the surface of PtNPs through two Pt-S bonds. The original antigen-recognizing function of the CDR restored on PtNPs was assessed by the specific inhibition of the enzymatic activity of lysozyme by the PtNP-CDR conjugates. ResultsAfter optimization of the peptide density on the surface of PtNPs and modification of PtNPs with polyethylene glycol (PEG), the resulted PtNP-based hybrid artificial antibody (PtNP-10PEG-30P1), dubbed Platinumbody, could bind specifically to lysozyme and significantly inhibit the activity of lysozyme. ConclusionThis is the first time that the fragment of a protein could refold on PtNPs. Together with the previous Goldbody and Silverbody, current work demonstrates that artificial proteins could be generally created by restoration of the native conformation of natural proteins fragments on NPs.

Objective To develop the functions and optimize the automatic monitoring module for arrhythmias of the adverse drug event active surveillance and assessment system-Ⅱ,in order to continuously improve the performance,enhance the monitoring efficiency,and explore the ways to optimize the module.Methods Expand and optimize the functions of the module,increase the customized configuration,and determine the optimal setting conditions;compare the optimized test data with the results of the evaluation studies on the automatic monitoring of drug-induced arrhythmias in large samples of medicated population previously,and verify the optimization extent as well as the accuracy of the module.Results In the new module optimized according to the characteristics of the monitoring population,the function of"mandatory medical order keywords"was added,and it was determined that the inclusion of 6 electrocardiogram examination-related medical order keywords with a frequency of not less than 2 occurrences was the optimal configuration condition for the optimization of the module;combining the results of the previous automatic monitoring and evaluation researches,the system functions were verified and compared under the conditions of using the whole drugs and 2 kinds of single drug.While there was no loss of true positive cases,the number of cases with system alarms decreased by 30.75％,80.13％and 90.82％,respectively,compared with that before the optimization of the module,and the positive predictive value was significantly improved.Conclusion After the function expansion and optimization,the automatic monitoring module of drug-induced arrhythmias significantly reduces the labor cost of case evaluation and keeps the accuracy of monitoring results constant;the new module can better adapt to the demands of different automatic monitoring modes and operates stably,which is more generalizable and flexible,and provides a new way of considering for the research and development of automatic monitoring modules.

Objective To obtain the occurrence and clinical characteristics of central nervous system adverse drug reactions(CNS-ADR)associated with three kinds of carbapenems,and to provide reference for clinical drug safety.Methods Based on adverse drug event active surveillance and assessment system-Ⅱ(ADE-ASAS-Ⅱ),retrospective automated monitoring of inpatients using imipenem,meropenem,and biapenem in a tertiary hospital from January 2022 to December 2022 was conducted.The incidence of carbapenem related CNS-ADR was calculated,and the basic conditions,disease conditions,drug use,occurrence time of ADR and symptoms of patients with CNS-ADR were analyzed by descriptive statistics.Results A total of 2 482 patients with 2 709 times of medication were included in this study,and a total of 93 positive cases of CNS-ADR occurred,with an overall incidence of 3.43％for all three medications,3.98％for imipenem,3.51％for meropenem,and 2.78％for biapenem.The indications for the 93 positive cases of CNS-ADR were mainly pulmonary infections(59.13％)and abdominal infections(25.80％);they occurred mostly within 7 days of the administration of the medication;with a variety of clinical manifestations,with anxiety/irritability being the most common,and epilepsy appearing most frequently in severe cases.Co-administration of proton pump inhibitors and cephalosporins accounted for a greater proportion of positive cases,50.54％of positive cases had a history of surgery,and 69.89％of positive cases were associated with electrolyte disturbances.Conclusion Clinical use of carbapenems should be based on the actual situation of the patient to develop an individualised drug regimen,and special attention should be paid to patients with comorbidities of renal disease,electrolyte disorders,and a history of previous surgery and neurological disorders,in order to reduce the risk of the occurrence of CNS-ADR.

Objective To investigate the osteogenic properties of a methacrylated gelatin(GelMA)/bone marrow mesenchymal stem cells(BMSCs)composite hydrogel applied to the skull defect area of rats and to provide an experi-mental basis for the development of bone regeneration biomaterials.Methods This study was approved by the Animal Ethics Committee of Nanjing University.A novel photocurable composite biohydrogel was developed by constructing photoinitiators[lthium phenyl(2,4,6-trimethylbenzoyl)phosphinate,LAP],GelMA,and BMSCs.The surface morphology and elemental composition of the gel were examined using scanning electron microscopy(SEM)and energy-dispersive X-ray spectroscopy(EDX).The compressive strength of the gel was evaluated using an electronic universal testing ma-chine.After in vitro culture for 1,2,and 5 days,the proliferation of the BMSCs in the hydrogels was assessed using a CCK-8 assay,and their survival and morphology were examined through confocal microscopy.A 5 mm critical bone de-ficiency model was generated in a rat skull.The group receiving composite hydrogel treatment was referred to as the Gel-MA/BMSCs group,whereas the untreated group served as the control group.At the 4th and 8th weeks,micro-CT scans were taken to measure the bone defect area and new bone index,while at the 8th week,skull samples from the defect ar-ea were subjected to H&E staining,van Gieson staining,and Goldner staining to evaluate the quality of bone regenera-tion and new bone formation.Results SEM observed that the solidified GelMA showed a 3D spongy gel network with uniform morphology,the porosity of GelMA was 73.41％and the pore size of GelMA was(28.75±7.13)μm.EDX results showed that C and O were evenly distributed in the network macroporous structure of hydrogel.The hydrogel compres-sion strength was 152 kPa.On the 5th day of GelMA/BMSCs culture,the cellular morphology transitioned from oval to spindle shaped under microscopic observation,accompanied by a significant increase in cell proliferation(159.4％,as determined by the CCK-8 assay).At 4 weeks after surgery,a 3D reconstructed micro-CT image revealed a minimal re-duction in bone defect size within the control group and abundant new bone formation in the GelMA/BMSCs group.At 8 weeks after surgery,no significant changes were observed in the control group's bone defect area,with only limited evi-dence of new bone growth;however,substantial healing of skull defects was evident in the GelMA/BMSCs group.Quan-titative analysis at both the 4-and 8-week examinations indicated significant improvements in the new bone volume(BV),new bone volume/total bone volume(BV/TV),bone surface(BS),and bone surface/total bone volume(BS/TV)in the GelMA/BMSCs group compared to those in the control group(P＜0.05).Histological staining showed continuous and dense formation of bone tissue within the defects in the GelMA/BMSCs group and only sporadic formation of new bone,primarily consisting of fibrous connective tissue,at the defect edge in the control group.Conclusion Photocur-ing hydrogel-based stem cell therapy exhibits favorable biosafety profiles and has potential for clinical application by inducing new bone formation and promoting maturation within rat skull defects.

Objective To understand the current situation and progress of doctor-patient communication curriculum research in the past 20 years in China based on the analysis of CiteSpace visualization software.Methods The literature related to doctor-patient communication courses was retrieved from CNKI,Wanfang Database and VIP database from January 2004 to October 2023.The authors,cooperating institutions and keywords in the retrieved results were analyzed using CiteSpace 6.2.R2 visualization software.Generate a visual co-occurrence map.Results A total of 1109 literatures meeting the requirements were included.The research focuses on four aspects:teaching reform,curriculum ideology and politics,medical humanities and doctor-patient relationship.Conclusion Since 2004,medical educators have been paying attention to the doctor-patient communication course,and the research on the teaching reform of this course has been steadily advancing.Curriculum ideology and politics,narrative medicine,humanistic literacy and teaching effect are the future research directions in this field.Medical colleges and universities should strengthen cooperation and strive to explore more diversified teaching methods to train medical talents who can cope with complex communication scenarios.

In order to evaluate the composition and distribution characteristics of inorganic elements in Laminaria japonica, this study employed inductively coupled plasma mass spectrometry(ICP-MS) to detect the inorganic elements and used high performance liquid chromatography tandem ICP-MS(HPLC-ICP-MS) to determine the content of different arsenic species in L. japonica from diffe-rent origins. Micro X-ray fluorescence(Micro-XRF) was used to determine micro-area distribution of inorganic elements in L. japonica. The results showed that the average content of Mn, Fe, Sr, and Al was high, and that of As and Cr exceeded the limits of the national food safety standard. According to the results of HPLC-ICP-MS, arsenobetaine(AsB) was the main species of As contained in L. japonica. The more toxic inorganic arsenic accounts for a small proportion, whereas its content was 1-4 times of the limit in the national food safety standard. The results of Micro-XRF showed that As, Pb, Fe, Cu, Mn, and Ni were mainly distributed on the surface of L. japonica. Among them, As and Pb had a clear tendency to diffuse from the surface to the inside. The results of the study can provide a basis for the processing as well as the medicinal and edible safety evaluation of L. japonica.
Arsenic/analysis* ; Chromatography, High Pressure Liquid/methods* ; Laminaria ; Mass Spectrometry/methods* ; Spectrum Analysis ; Trace Elements/analysis*