An Insulin-Modified pH-Responsive Nanopipette Based on Ion Current Rectification.

The properties of nanopipettes largely rely on the materials introduced onto their inner walls, which allow for a vast extension of their sensing capabilities. The challenge of simultaneously enhancing the sensitivity and selectivity of nanopipettes for pH sensing remains, hindering their practical applications. Herein, we report insulin-modified nanopipettes with excellent pH response performances, which were prepared by introducing insulin onto their inner walls via a two-step reaction involving silanization and amidation. The pH response intensity based on ion current rectification was significantly enhanced by approximately 4.29 times when utilizing insulin-modified nanopipettes compared with bare ones, demonstrating a linear response within the pH range of 2.50 to 7.80. In addition, insulin-modified nanopipettes featured good reversibility and selectivity. The modification processes were monitored using the I-V curves, and the relevant mechanisms were discussed. The effects of solution pH and insulin concentration on the modification results were investigated to achieve optimal insulin introduction. This study showed that the pH response behavior of nanopipettes can be greatly improved by introducing versatile molecules onto the inner walls, thereby contributing to the development and utilization of pH-responsive nanopipettes.

Diagnostic and grading criteria for androgenetic alopecia using dermoscopy.

OBJECTIVES: To establish accurate and objective dermoscopic diagnostic criteria and grading standards for males and females with androgenetic alopecia (AGA). METHODS: Twenty patients each with AGA, diffuse alopecia areata, telogen effluvium, and healthy controls were enrolled in the current study. In addition, 60 patients with grades F1/V1, F2/V2, and F3/V3 AGA (20 cases each) were enrolled. The patients underwent dermoscopic examinations. The sensitivity and specificity of the diagnostic criteria were based on the 60 AGA and 60 non-AGA. In addition, 150 patients diagnosed with AGA clinically and by dermoscopy were enrolled to calculate the accuracy of the grading criteria. RESULTS: The diagnostic criteria included primary, secondary, and exclusion criteria. The grading criteria included three indices, which divided the severity of AGA into grades 1, 2, and 3. The sensitivity and specificity of the diagnostic criteria were 98.3% and 96.7% respectively. The accuracy of grade 1, 2, and 3 dermoscopic grading criteria were 96%, 92%, and 100% respectively, with a total accuracy of 96%. LIMITATIONS: To test the diagnostic and grading criteria, more patients need to be collected. CONCLUSIONS: The dermoscopic diagnostic and grading criteria are objective with good accuracy, which could provide a reasonable basis for the early diagnosis, grading treatment, and improved prognosis for AGA.

A retrospective study on the clinical features of skin lesions in Chinese acquired digital fibrokeratoma patients.

BACKGROUND: Acquired digital fibrokeratoma (ADFK) is an uncommon benign fibro-epithelioma, which is rarely reported in China. AIMS: To analysis the clinical features of ADFK in Chinese people from current cases. METHODS: From December 2019 to October 2021, there were 21 patients diagnosed with ADFK, we made a retrospective analysis on the clinical features of skin lesions in them. To summarize the clinical morphology, location, and surgical follow-up of ADFK. RESULTS: We concluded that ADFK is more common in females than males on the hands (7:3), while the male-to-female ratio is largely the same in feet (6:5). It occurs more frequently on the third finger (60%) and first toe (45.5%). As to clinical morphology, it is typically rod-shaped (52.4%), followed by dome-shaped (42.8%) and wart-shaped (4.8%). It is typically dome-shaped on the hands (80%) and rod-shaped on the feet (81.8%). In terms of location on the fingers (toes), such skin lesions are most common at the proximal nail fold (52.4%), which can also occur at the nail matrix (14.3%), periungual area (23.8%), and subungual area (9.5%). Nevertheless, this ratio also varies on the hands and feet. All patients got surgical excision of the skin lesion, who were followed up for 6-12 months, without recurrence. CONCLUSIONS: Most ADFKs are associated with trauma, whose clinical features are related to location and gender. ADFKs on the hands are different from those on the feet regarding clinical morphology and location on fingers (toes), and surgery is effective in treating this condition.

Patient Needs in Psoriasis Treatment and their Influencing Factors: A Nationwide Multicentre Cross-Sectional Study in China.

Background: The management and treatment of psoriasis has rarely considered patient needs, which are numerous, multi-dimensional and are of great importance to improving treatment outcomes. Objectives: This study aimed to evaluate and compare the patients' needs for psoriasis treatment and identify factors predicting the need to make patient-centred decisions about treatment. Materials and Methods: This nationwide multicentre cross-sectional study included subjects between October 2020 and August 2021. The status quo of the needs in psoriasis treatment and their influencing factors were analysed mainly using the Chi-square test and binary logistic regression. Results: Information on sociodemographic and clinical characteristics were obtained. Factor analysis of a specially designed questionnaire showed that rapid skin clearance, reduced treatment expense and fewer hospital visits or treatment time were the first three patient needs in psoriasis treatment. Several influencing factors were important including the sociodemographic characteristics of gender, marital status, education level and family history, special location of skin lesions, dermatology life quality index (DLQI), Investigator's Global Assessment modified 2011 (IGA mod 2011), condition of the episode, clinical type of psoriasis, seasonal exacerbation and therapy. Conclusions: Patients with psoriasis pursued a wide range of treatment goals, with the most desired being rapid skin clearance, reduced treatment expense and time-saving. Paying attention to sex, marital status, education level, the special location of skin lesions and the DLQI will help dermatologists develop patient-centred treatment, meet the patient's needs and eventually improve the treatment outcomes.

Genome-wide analysis of Chinese keloid patients identifies novel causative genes.

Background: Keloids are benign skin tumors that appears on skin lesions in humans. Keloids are characterized by invasive tumor growth and are highly prone to recurrence after treatment. The incidence of keloids is ethnically specific; however, the molecular mechanism underlying the incidence of keloids in the Chinese population remains unclear. To date, no reports appear to have been published on the molecular characteristics underlying keloids in the Chinese population from the perspective of whole-genome sequencing. Methods: In this study, we collected keloid samples from 9 keloid patients underwent surgery in the Department of Dermatology, The First Affiliated Hospital of Soochow University, paired them to normal skin tissues, and performed whole-exome sequencing. The average depth of the samples was 1,200×, and the average exome coverage was 98.90%. Results: The bioinformatics analysis identified 3,125 single nucleotide variants (SNVs) and 299 insertions/deletions (InDels). The major mutation characteristics of the SNVs were C > A and C > T. The non-synonymous SNV types included stopgain, and stoploss. The non-synonym InDels included frameshift deletion, frameshift insertion, and stopgain. We also found a total of 67,873 copy number variations (CNVs) in the samples. The genes with the highest mutation frequency included mucin 4 (MUC4) (55.6%), tubulin tyrosine ligase like 12 (TTLL12) (33.3%), calcium voltage-gated channel subunit alpha1 (CACNA1C) (33.3%), and mucin 12 (MUC12) (33.3%). The average tumor mutation burden (TMB) was 289 mutations/million base pair (MB). The Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis revealed that the mutated genes were mainly concentrated in micro ribonucleic acids in cancer and the calcium signaling pathway. The Gene Ontology (GO) analysis showed that mutant genes were mainly concentrated in binding cells, cell parts, and cellular processes. Conclusions: Whole-exome sequencing was performed in the Chinese keloid patients and some potential candidate genes related to keloid occurrence and development were identified, which may provide new molecular targets for the clinical diagnosis and treatment of keloid patients.

Diagnosis and differential diagnosis of dermatofibrosarcoma protuberans: Utility of high-resolution dynamic contrast-enhanced (DCE) MRI.

BACKGROUND: Dermatofibrosarcoma protuberans (DFSP) is a kind of low-grade malignant spindle cell neoplasm, the diagnosis, and treatment, which have markedly attracted clinicians' attention for its repeated recurrence. High-resolution magnetic resonance imaging (HR-MRI) has shown unique capabilities in diagnosis of various cutaneous tumors. MATERIALS AND METHODS: Data of 29 patients with clinically suspected DFSPs and undergoing dynamic contrast-enhanced (DCE) HR-MRI preoperatively were prospectively collected. The HR-MRI qualitative features were evaluated and compared. The DCE-associated quantitative parameters and the time-signal intensity curve (TIC) types were provided using DCE sequences. RESULTS: A total of 7 DFSPs, nine dermatofibromas (DF, including four cases of cellular variant [CDF]), 12 keloids, and one nodular fasciitis were enrolled. DFSP showed the largest major diameter and the deepest depth. Five DFSPs (71.4%) showed ill-defined margins as well as infiltration of peripheral adipose. All DFSPs showed irregular shape. Most DFSPs presented hyperintensity on T2 WI (71.4%) and iso-intensity on T1 WI (85.7%). Six cases (85.7%) had significant enhancement, and six cases (85.7%) had homogeneous enhancement. There were significant differences of Ktrans , Kep , Ve and iAUC values among DFSPs, DFs, and keloids, and DFSP had the highest values for these parameters. Six DFSPs (85.7%) and four CDFs (100%) showed type-III TICs, while the other lesions showed type-Ⅰor type-Ⅱ TICs. CONCLUSIONS: DCE-HR-MRI could show the growth characteristics of DFSPs, which was of great value for the diagnosis and differential diagnosis of DFSPs and was helpful for the determination of treatment options, thereby to improve the prognosis of patients.

Influence of bFGF on in vitro expansion and chondrogenic construction of articular cartilage-derived progenitor cells.

Background: Articular cartilage-derived progenitor cells (ACPCs) possess the properties of both chondrocytes and bone marrow mesenchymal stem cells (BMSCs). However, the number of ACPCs in articular cartilage is low, and an effective culture system is needed for their expansion. Basic fibroblast growth factor (bFGF) promotes the expansion of chondrocytes and BMSCs, as well as the chondrogenic differentiation of BMSCs. Therefore, the aim of this study was to clarify whether bFGF could be used for in vitro expansion of ACPCs and whether bFGF promoted chondrogenic construction of ACPCs. Methods: We applied the fibronectin adhesion method to sort mice ACPCs and compared the proliferative, osteogenic, and chondrogenic abilities of ACPCs by adding various concentration of bFGF (0, 2, and 5 ng/mL) to the cell culture medium. Then used the best system to construct cartilage with ACPCs in vitro and in vivo. Results: The results indicated that bFGF promoted ACPCs proliferation, inhibited osteogenesis, and promoted chondrogenesis, and that a cell culture system containing 2 ng/mL bFGF was optimal for these effects. ACPCs constructed cartilage using the filtered culture system presented homogeneous cartilaginous histological structure in vitro and in vivo. Conclusions: By applying this cell culture system, homogenous cartilage tissue was constructed in vitro and in vivo by chondrogenic induction, which provides a stable cell expansion culture method for the application of ACPCs in cartilage repair.

Nail matrix scars that result in nail dystrophy resemble cutaneous scars: A new nail trauma model.

BACKGROUND: Few studies have described how the injury affects the nail soft tissue under the nail plate. Nail matrix scar is poorly known. OBJECTIVE: To establish a stable rat nail loss model in a simple way, and to discuss the comparability of this model. METHODS: A sterile cotton swab dipped in a 10% NaOH solution was used to burn the entire nail matrix and bed plane region, and the specimens were examined on day 3, 7, 14, and 28. RESULTS: After avulsion of the nail plate, the eponychia and matrix stuck together without any tissue destruction. On day 28, all claws of the experimental group were observed to be permanently damaged, except for one claw malformed regeneration. All impaired nail regeneration had deficiency or functional loss of NMSCs and shared similar characteristics with the cutaneous scars. CONCLUSIONS: The scar formation of nail matrix was a fundamental reason to nail deficiency of rat or human, providing a research basis for further mechanism or treatment study of nail defect diseases.

Three-dimensional printing in a patient with pulmonary artery pseudoaneurysm and complex congenital heart disease-A case report.

3D-printing is a powerful tool in patients with complex anatomy undergoing cardiac surgery.

Hemoperfusion with HA380 in acute type A aortic dissection patients undergoing aortic arch operation (HPAO): a randomized, controlled, double-blind clinical trial.

BACKGROUND: Cardiopulmonary bypass (CPB) is an important cause of significant systemic inflammatory response syndrome (SIRS) in the surgical treatment of acute type A aortic dissection (ATAAD). In patients with arch vessel involvement, extensive surgical repairs often necessitate prolonged use of CPB and results in extensive inflammatory responses. Cytokines and chemokines released during CPB contribute to the progression of SIRS, increase perioperative complications, and negatively impact surgical outcomes. A cytokine adsorber (HA380) is expected to reduce the level of cytokines during CPB, which may decrease both intraoperative and postoperative inflammation. The purpose of this study is to investigate if HA380 is able to reduce the levels of inflammatory cytokines and decrease perioperative complications in ATAAD patients undergoing CPB and deep hypothermic circulatory arrest (DHCA). METHODS: This study is a single-center, randomized, controlled, double-blind clinical trial. The study aims to recruit 88 patients with ATAAD and aortic arch involvement who will undergo CPB and DHCA to repair the dissected aorta. Patients will be randomized equally into the CPB/DHCA only group (control group) and the CPB/DHCA + HA380 hemoperfusion group (intervention group), with 44 patients each. Patients in the control group will undergo CPB and DHCA only, while patients in the intervention group will undergo continuous hemoperfusion with HA380, in addition to CPB and DHCA. The primary outcome is a composite of major perioperative complications. The secondary outcomes include related inflammatory markers, coagulation parameters, and minor perioperative complications. To comprehensively evaluate the effect of hemoperfusion on the perioperative outcomes, we will also determine if there are differences in perioperative all-cause mortality, length of ICU stay, and total hospitalization costs. DISCUSSION: In the current trial, hemoperfusion will be applied in patients undergoing CPB and DHCA for repair of the aorta involving the aortic arch. This trial aims to test the safety and efficacy of our hemoperfusion device (HA380) in such settings. Upon completion of the trial, we will determine if HA380 is effective in reducing perioperative proinflammatory cytokine levels. Further, we will also verify if reduction in the proinflammatory cytokine levels, if present, translates to improvement in patient outcomes. TRIAL REGISTRATION: ClinicalTrials.gov NCT04007484 . Registered on 1 July 2019 (retrospectively registered).

S-shaped wound closure following the excision of 2 adjacent pigmented nevi.

BACKGROUND: The main goal of excision of a pigmented nevus is to achieve an esthetically pleasing result. A single nevus can be removed by simple excision, whereas S-shaped suture can be used for the excision of 2 adjacent nevi. However, the choice of suturing method is based on the experience of the dermatologic surgeon, as there is no uniform standard for suture following the excision of 2 adjacent nevi. The aim of the present study was to determine whether S-shaped wound closure is appropriate for the excision of 2 adjacent nevi. METHODS: The outcomes of 21 patients who underwent simultaneous resection of 2 adjacent nevi were retrospectively reviewed. Of these patients, 17 chose S-shaped suture and 4 chose direct suture. Patients were followed-up for more than 6 months to review their postoperative scars. Differences between the 2 methods were compared based on the patient and observer scar assessment scale. Diameters and the proportional relationship between the 2 nevi were analyzed. RESULTS: Patients who underwent S-shaped wound closure surgery were more satisfied compared to those who had direct suturing (P<0.05); the nevus diameter-to-spacing diameter ratio was 0.68±0.35:1:0.99±0.56 in the S-shaped wound closure group. CONCLUSIONS: S-shaped wound closure following the excision of 2 adjacent nevi resulted in better patient satisfaction than the conventional direct suturing method.

Repair of articular cartilage defects with acellular cartilage sheets in a swine model.

Acellular cartilage sheets (ACSs) have been demonstrated as a good biomaterial for cartilage regeneration as a result of their natural cartilage matrix components, cartilage-specific structures, and good biocompatibility. However, it remains unknown whether allogeneic ACSs could promote cartilage regeneration and repair cartilage defects in a large animal model. The current study explored the feasibility of repairing articular cartilage defects using ACS scaffold with or without autologous bone marrow stromal cells (BMSCs) in a swine model. According to the current results, ACSs retained natural cartilage structure, primary cartilage matrices, and cartilage-specific growth factors. After cell seeding, ACSs presented good biocompatibility with BMSCs, which produced abundant extracellular matrix (ECM) proteins to cover the lacuna structures. In vivo results indicated that ACSs alone could induce endogenous host cells to regenerate cartilage and achieve generally satisfactory repair of cartilage defects at 6 months post-operation, including good interface integration and cartilage-specific ECM deposition. After combination with autologous BMSCs, BMSC-ACS constructs achieved more satisfactory repair of cartilage defects even without in vitro pre-induction of chondrogenesis. More importantly, all defects in both BMSC-ACS and ACS-only groups showed enhanced cartilage regeneration compared with BMSC-polyglycolic acid and blank groups, which mainly exhibited fibrogenesis in defect areas. Collectively, the current results indicate that ACSs can efficiently repair articular cartilage defects by promoting chondrogenic differentiation of BMSCs or inducing endogenous chondrogenesis in situ, thus serving as a good cartilage regeneration scaffold for recovery of articular function.

The influence of Chm-I knockout on ectopic cartilage regeneration and homeostasis maintenance.

Ectopic ossification of mesenchymal stem cell (MSC) regenerated cartilage has greatly restricted its application in repairing subcutaneous cartilage defects (such as nasal or auricular). Different from MSCs, chondrocytes can maintain stable chondrogenic phenotype in ectopic microenvironment, which was speculated to be related with the existence of antiangiogenic factors such as Chondromodulin-I (Chm-I). Therefore, the purpose of this study was to illustrate whether Chm-I was indispensable for stable ectopic chondrogenesis by chondrocyte, which may help to solve the problem of MSC ectopic ossification in the future. The current study demonstrated that Chm-I knockout did not obviously influence articular cartilage development in situ. However, native articular cartilage from Chm-I knockout (Chm-I(-/-), KO), but not wild-type (WT) mice, showed obvious ossification after subcutaneously implanted into nude mice for 16 days. Interestingly, cell morphology, cartilage-specific matrix expression, and pellet culture demonstrated that Chm-I knockout had no obvious influence on the phenotype, function, and chondrogenic ability of chondrocytes in vitro, except that cells in the WT group proliferated a little faster than those in the KO group. Nevertheless, Chm-I knockout directly interfered with in vivo ectopic cartilage regeneration when chondrocytes were subcutaneously injected into nude mice with matrigel. Moreover, Chm-I knockout obviously compromised ectopic stability of in vitro regenerated cartilage after subcutaneous implantation. These findings indicated that Chm-I was an indispensable factor for ectopic cartilage regeneration and the maintenance of cartilage homeostasis, which may provide a clue for solving the stability problem of MSC regenerated cartilage in ectopic niche. In addition, this study also provides a novel model based on tissue engineering strategy to properly evaluate the function of other targeted genes.

The influence of Gelatin/PCL ratio and 3-D construct shape of electrospun membranes on cartilage regeneration.

Scaffolds play an important role in directing three-dimensional (3-D) cartilage regeneration. Our recent study reported the potential advantages of electrospun gelatin/polycaprolactone (GT/PCL) membranes in regenerating 3-D cartilage. However, it is still unknown whether the changes of GT/PCL ratio have significant influence on 3-D cartilage regeneration. To address this issue, the current study prepared three kinds of electrospun membranes with different GT/PCL ratios (70:30, 50:50, 30:70). Adhesion and proliferation of chondrocytes on the membranes were examined to evaluate biocompatibility of the membranes. Cartilage with different 3-D shapes was engineered to further evaluate the influences of GT/PCL ratio on cartilage regeneration. The current results demonstrated that all the membranes with different GT/PCL ratios presented good biocompatibility with chondrocytes. Nevertheless, the high PCL content in the membranes significantly hampered early 3-D cartilage formation at 3 weeks in vivo. Unexpectedly, at 12 weeks, all the cylinder-shaped constructs formed mature cartilage-like tissue with no statistical differences among groups. To our surprise, ear-shaped cartilage regeneration obtained quite different results again: the high PCL content completely disrupted cartilage regeneration even at 12 weeks, and only the least PCL content group formed homogeneous and continuous cartilage with a satisfactory shape and elasticity similar to human ear. All these results indicated that the high PCL content was unfavorable for 3-D cartilage regeneration, especially for the cartilage with a complicated shape, and that GT/PCL 70:30 might be a relatively suitable ratio for ear-shaped cartilage regeneration. The research models established in the current study provide detailed information for cartilage and other tissue regeneration based on electrospun GT/PCL membranes.

The impact of PLGA scaffold orientation on in vitro cartilage regeneration.

The success of in vitro cartilage regeneration provides a promising approach for cartilage repair. However, the currently engineered cartilage in vitro is unsatisfactory for clinical application due to non-homogeneous structure, inadequate thickness, and poor mechanical property. It has been widely reported that orientation of scaffolds can promote cell migration and thus probably contributes to improving tissue regeneration. This study explored the impact of microtubular oriented scaffold on in vitro cartilage regeneration. Porcine articular chondrocytes were seeded into microtubule-oriented PLGA scaffolds and non-oriented scaffolds respectively. A long-term in vitro culture followed by a long-term in vivo implantation was performed to evaluate the influence of scaffold orientation on cartilage regeneration. The current results showed that the oriented scaffolds could efficiently promote cell migration towards the inner region of the constructs. After 12 weeks of in vitro culture, the chondrocyte-scaffold constructs in the oriented group formed thicker cartilage with more homogeneous structure, stronger mechanical property, and higher cartilage matrix content compared to the non-oriented group. Furthermore, the in vitro engineered cartilage based on oriented scaffolds showed better cartilage formation in terms of size, wet weight, and homogeneity after 12-week in vivo implantation in nude mice. These results indicated that the longitudinal microtubular orientation of scaffolds can efficiently improve the structure and function of in vitro engineered cartilage.

Xenogeneic chondrocytes promote stable subcutaneous chondrogenesis of bone marrow-derived stromal cells.

The local microenvironment may change the ultimate fate of engineered cartilage differentiated from bone marrow stromal cells (BMSCs) after subcutaneous implantation. Chondrogenically differentiated BMSCs directed by growth factors or low-intensity ultrasound are apt to fibrose or vascularize in the subcutaneous environment, while BMSCs implanted in articular cartilage defects can form stable cartilage. We hypothesized that chondrocytes would provide an ideal chondrogenic environment, and thus promote the maintenance of the chondrocytic phenotype in ectopia. To test this hypothesis, we developed a new method to promote chondrocyte development from BMSCs in a chondrogenic environment produced by xenogeneic chondrocytes and compared the subcutaneous chondrogenesis of BMSCs mediated by xenogeneic chondrocytes with that produced by growth factors. These results indicate that subcutaneous chondrogenesis of BMSCs directed by xenogeneic chondrocytes is more effective than that induced by growth factors. BMSCs induced by xenogeneic chondrocytes formed relatively mature cartilage before or after implantation, following 4 weeks of culture, which reduced the induction time in vitro and led to maintenance of a stable cartilage phenotype after subcutaneous implantation.

Abnormal glucose regulation in pyrethroid pesticide factory workers.

The purpose of this study was to investigate associations between pyrethroids occupational exposures, and risk of abnormal glucose regulation. Data from total of 3080 subjects in two pesticide factories were used. This was a population-based case-controlled study in China. In total, 18.3% of subjects with impaired glucose regulation (IGR) and 6.5% of subjects with diabetes, and the prevalence of abnormal glucose regulation was 24.8%, 86 subjects had known type 2 diabetes and 114 had newly diagnosed diabetes. The prevalence of subjects with abnormal glucose regulation increased from 21.3% in the controls to 29.3% in the exposures (χ² = 33.182, P < 0.001). Multivariate logistic regression was used to control potential confounders and calculate odd ratios as the estimate of effect. An indication of increased risk for abnormal glucose regulation was noted for exposure to pyrethroids (OR = 1.482, 95%CI = 1.238-1.774). Abnormal glucose regulation is common in subjects exposed to pyrethroids. The present investigation indicates the adverse health effects of pyrethroids are underestimated.