Multifaceted Characterization of Human Embryonic Stem Cell-Derived Mesenchymal Stem/Stromal Cells Revealed Amelioration of Acute Liver Injury in NOD-SCID Mice.

Human embryonic stem cells (hESCs) are advantaged sources for large-scale and homogeneous mesenchymal stem/stromal cells (MSCs) generation. However, due to the limitations in high-efficiency procedures for hESC-MSCs induction, the systematic and detailed information of mesengenesis and early MSC development are largely obscure. In this study, we took advantage of the well-established twist-related protein 1 (TWIST1)-overexpressing hESCs and two small molecular cocktails (CHIR99021, decitabine) for high-efficient MSC induction. To assess the multidimensional biological and transcriptomic characteristics, we turned to cellular and molecular methods, such as flow cytometry (FCM), quantitative reverse transcription-polymerase chain reaction (qRT-PCR), in vitro tri-lineage differentiation, cytokine secretion analysis, in vivo transplantation for acute liver injury (ALI) management, and bioinformatics analyses (eg, gene ontology-biological processes [GO-BP], Kyoto Encyclopedia of Genes and Genomes [KEGG], HeatMap, and principal component analysis [PCA]). By combining TWIST1 overexpression (denoted as T) and the indicated small molecular cocktails (denoted as S), hESCs high-efficiently differentiated into MSCs (denoted as TS-MSCs, induced by T and S combination) within 2 weeks. TS-MSCs satisfied the criteria for MSC definition and revealed comparable tri-lineage differentiation potential and ameliorative efficacy upon ALI mice. According to RNA-sequencing (SEQ) analysis, we originally illuminated the gradual variations in gene expression pattern and the concomitant biofunctions of the programmed hESC-MSCs. Overall, our data indicated the feasibility of high-efficient generation of hESC-MSCs by TWIST1 and cocktail-based programming. The generated hESC-MSCs revealed multifaceted in vivo and in vitro biofunctions as adult BM-MSCs, which collectively suggested promising prospects in ALI management in future.

A comparative study of the predictive value of four models for death in patients with severe burns.

OBJECTIVE: To assess the prognostic value of the Ryan score, Belgian Outcome of Burn Injury (BOBI) score,revised Baux (rBaux) score, and a new model (a Logit(P)-based scoring method created in 2020) for predicting mortality risk in patients with extremely severe burns and to conduct a comparative analysis. METHODS: A retrospective analysis was conducted on 599 burn patients who met the inclusion criteria and were admitted to the burn unit of the First Affiliated Hospital of Nanchang University from 2017 to 2022. Relevant information was collected, and receiver operating characteristic (ROC) curves, calibration curves, and decision curve analysis (DCA) were plotted for each of the four models in assessing mortality in these burn patients using both age-stratified and unstratified forms. The ROC curve section was further compared with the area under the curve (AUC), optimal cutoff value, as well as its sensitivity and specificity. Additionally, the quality of the AUC was assessed using the Delong test. RESULT: Among the patients who met the inclusion criteria, 532 were in the survival group and 67 in the death group. Irrespective of age stratification, the novel model exhibited superior performance with an AUC of 0.868 (95% CI: 0.838-0.894) among all four models predicting mortality risk in included patients, and also demonstrated better AUC quality than other models; the calibration curves showed that the accuracy of all four models was good; the DCA curves showed that the clinical utility of the novel model and rBuax score were better. In the comparison of four scoring models across different age groups, the new model demonstrated the largest AUC in both 0-19 years (0.954, 95% CI 0.914-0.979) and 20-59 years groups (0.838, 95% CI 0.793-0.877), while rBuax score exhibited the highest AUC in ≥ 60 years group (0.708, 95% CI of 0.602-0.800). The calibration curves showed that the four models exhibited greater accuracy within the age range of 20-59 years, while the DCA curves indicated that both the novel model and rBuax score scale displayed better prediction in both the 20-59 and ≥ 60 years groups. CONCLUSIONS: All four models demonstrate accurate and effective prognostication for patients with severe burns. Both the novel model and rBaux score exhibit enhanced prediction utility. In terms of the model itself alone, the new model is not simpler than, for example, the rBaux score, and whether it can be applied clinicallyinvolves further study.

A Novel Preoperative Design to Address Dermatochalasis in Asian Upper Blepharoplasty.

BACKGROUND: The preoperative design for the amount of skin excision of the upper eyelid is a common procedure in Asian blepharoplasty, but there lack of an effective method addressing dermatochalasis to acquire esthetically pleasing results. Our aim was to propose an alternative technique to determine the skin excision combined with the esthetics of eyes for correcting skin laxity and therefore to create attractive double eyelids. MATERIALS AND METHODS: The preoperative invaginating-simulating design combined with esthetic criteria for determining the amount of excised skin were performed during blepharoplasty. The Strasser grading system and the Global Aesthetic Improvement Scale were evaluated by analyzing the preoperative and 6-month-postoperative photographs. RESULTS: One hundred forty-two patients were included. The general outline of the "optimal incision" took on a knife in shape with a mean of 2.2±3.32 points of Strasser grading score. A total of 130 of 142 patients (91.5%) were judged as "good results" and 12 of 142 patients (8.5%) were judged as "mediocre". The Global Aesthetic Improvement Scale showed a significant cosmetic improvement with the result of 89.4%(127 of 142 patients) for "very much improved", 7.8% for "much improved" and other patients for "improved". No severe complications were observed. CONCLUSIONS: This preoperative design approach has been proven to be effective to address dermatochalasis (especially for lateral hooding) by simulating the expected appearance of a double eyelid combined with esthetic criteria of eyes simultaneously, which can contribute to achieving upper-lid rejuvenation and beautiful and natural outcomes.

Selective Repair of Motor Branches in the Femoral Nerve by Transferring the Motor Branches of Obturator Nerve: An Anatomical Feasibility Study.

BACKGROUND: Anterior branch of the obturator nerve transfer has been proven as an effective method for femoral nerve injuries, but the patient still has difficulty in rising and squatting, up and downstairs. Here, we presented a novel neurotization procedure of selectively repairing 3 motor branches of the femoral nerve by transferring motor branches of the obturator nerve in the thigh level and assessing its anatomical feasibility. METHODS: Eight adult cadavers (16 thighs) were dissected. The nerve overlap distance between the gracilis branch and the rectus femoris (RF) branch, the adductor longus (AL) branch and the vastus medialis (VM) branch, as well as the adductor magnus (AM) branch and the vastus intermedius (VI) branch were measured. Also, the axon counts of the donor and recipient nerve were evaluated by histological evaluation. RESULTS: In all specimens, nerve overlap of at least 2.1 cm was observed in all 16 dissected thighs between the donor and recipient nerve branches, and the repair appeared to be without tension. There is no significant difference in the axon counts between gracilis branch (598 ± 83) and the RF branch (709 ± 151). The axon counts of the AL branch (601 ± 93) was about half of axon counts of the VM branch (1423 ± 189), and the axon counts of AM branch (761 ± 110) was also about half of the VI branch (1649 ± 281). CONCLUSIONS: This novel technique of the combined nerve transfers below the inguinal ligament, specifically the gracilis branch to the RF branch, the AL branch to the VM branch, and the AM branch to the VI branch, is anatomically feasible. It provides a promising alternative in the repair of femoral nerve injuries and an anatomical basis for the clinical application of motor branches of the obturator nerve transfer to repair the motor portion of the injured femoral nerve.

Sustainable access to benzothiophene derivatives bearing a trifluoromethyl group via a three-component domino reaction in water.

A catalyst-free three-component domino reaction was developed for the synthesis of benzothiophene fused pyrrolidones bearing a CF3 group for the first time. The notable advantages of this strategy over the existing methods include the use of water as a solvent at room temperature, transition metal-free conditions, a broad substrate scope, and easy scale-up synthesis. More importantly, the benzothiophene derivatives have been found to show potent anticancer activities using the Cell Counting Kit-8 (CCK-8) assay.

Contralateral obturator nerve transfer for femoral nerve restoration: a case report.

BACKGROUND: Femoral nerve injury may occur in severe traffic accident injuries with pelvic fracture. Sural nerve grafts or ipsilateral obturator nerve transfer may be used to restore femoral nerve function. We report a new procedure transferring the contralateral obturator nerve to restore femoral nerve function. CASE DESCRIPTION: A 30 year-old male suffering complete lumbar plexus rapture received a contralateral obturator nerve transfer in our hospital. At 2 years follow up he had gained Medical Research Council Grade 3 muscle strength in his 23th months follow-up, with normal gait, Lower Extremity Functional Scale score of 58.75% and Femoral Nerve Motor Function Scale score 61%. CONCLUSION: The contralateral obturator nerve transfer is a reliable alternative if the nerve graft or ipsilateral obturator nerve cannot be performed.

A New Triangular Rotation and Advancement Pulp Flap for Lateral Oblique Fingertip Defect.

The fingertip is one of the most common sites of traumatic injuries faced by hand surgeons. In cases of lateral oblique amputation, only limited alternatives are available for reconstruction. This study introduced a new method involving rotation and use of an advancement pulp flap for covering lateral oblique defect and evaluated its outcome. METHOD: A series of 12 patients with 14 lateral oblique fingertip defects were recruited in this study. All fingertips were unreplantable and were injured distal to the proximal one-third of nail bed, with phalanx exposed. All cases received surgical reconstruction using a triangular rotation and advancement pulp flap. Static 2-point discrimination, cold intolerance, pain, hypersensitivity, range of motion, and aesthetic satisfaction were evaluated 6 months to 12 months postoperation. RESULT: Bone defect was noted in 7 cases. The area of defect was 10×7-20×12 mm2, and the angle of defect was 30-60 degrees. Mean follow-up was 14.3 months. No hook nail deformity, cold intolerance, and hypersensitivity were observed. One patient complained about pain postoperation, demanding a second operation. Static 2-point discrimination was between 5 and 8 mm in all cases. Range of motion of distal interphalangeal joint recovered to 20-45 degrees at the last follow-up. No stiffness was observed in the interphalangeal or metacarpophalangeal joints. All patients were satisfied with the appearance of the flap. CONCLUSION: The triangular rotation and advancement pulp flap is simple, safe, and reliable for treating lateral oblique defect of fingertip, providing scope for anatomical reconstruction and fair sensation and aesthetic recovery.

Enhanced MR neurography of the lumbosacral plexus with robust vascular suppression and improved delineation of its small branches.

PURPOSE: To evaluate whether gadolinium enhanced 3D SPACE STIR sequence technique increases the visualization of the lumbosacral plexus (LSP) and its small branches. METHODS: A retrospective study was performed on 24 patients who had underwent 3D SPACE STIR sequences scan with and without the administration of gadolinium contrast. In this study, we focused on the healthy sides of the LSP and its branches in each patient. The contrast ratio (CR), contrast-to-noise ratio (CNR) and signal-to-noise ratio (SNR) were objectively calculated by two experienced radiologists. The subjective visualization scores of the branches that were vitally important to therapeutic decision-making including femoral nerves, obturator nerves, lumbosacral trunks, superior gluteal and extra-pelvic sciatic nerves, were assessed using post-processing images. RESULTS: Of the 24 subjects, all LSP nerve roots, femoral nerves, lumbosacral trunks and sciatic nerves were illustrated on both contrast-enhanced and non-contrast images. The enhanced images were found to have higher nerve to vein CNRs compared to non-contrast images. Compared to non-contrast images, the CRs of nerves versus surrounding fat tissues, bones, veins and muscles were improved in contrast-enhanced images, while the SNRs were better but not significantly so. Targeted maximum intensity projection (MIP) nerves including femoral, obturator, superior gluteal and extra-pelvic sciatic nerves obtained significantly higher subjective scores when gadolinium was administered. CONCLUSIONS: The gadolinium enhanced 3D SPACE STIR sequence provided superior vascular suppression, resulting in increased conspicuity of LSP and its small branches. Altogether, this shows great potential for therapeutic decision-making in traumatic LSP lesions cases.

Different Surgical Reconstructions for Femoral Nerve Injury: A Clinical Study on 9 Cases.

BACKGROUND: Femoral nerve palsy can cause loss in quadriceps function and knee extension disability, which may lead to severe lower extremity impairment. The obturator nerve trunk transfer in the pelvic, the obturator nerve mortal branches transfer out of the pelvic, along with nerve graft, was introduced years ago to restore femoral nerve function. However, the outcomes of these procedures have never been compared. The aims of this study were to give our experiences in surgical reconstruction for femoral nerve injury and to compare the outcomes of different approaches. METHODS: Nine patients with complete femoral nerve injury have been enrolled in this study between March 2012 and July 2016. All patients were followed up for at least 2 years after surgical intervention for sural nerve graft (n = 3), obturator trunk transfer in the pelvic (n = 2), or obturator nerve mortal branches transfer out of the pelvic (n = 4). RESULTS: All patients gained satisfactory quadriceps Medical Research Council grade (M3-M4+) after more than 2 years of follow-up. The sural nerve graft led to the earliest recovery on average, followed by obturator nerve mortal branches transfer in the thigh level and then obturator nerve trunk transfer in the pelvic. The functional outcomes, demonstrated by Lower Extremity Functional Scale and Femoral Nerve Motor Function Scale scores, also showed that the sural nerve graft was the best on average, followed by obturator nerve trunk transfer in the pelvic and then obturator nerve mortal branches transfer in the thigh level. CONCLUSIONS: Our results indicate that all these 3 procedures are safe and reliable ways to reconstruct femoral nerve function and can be applied to patients with different kinds of injuries. The sural nerve graft should be considered in the first place and the obturator nerve transfer at different level (trunk transfer in the pelvic or mortal branches transfer out of the pelvic) can be performed as the alternative.

Contralateral C7 transfer via both ulnar nerve and medial antebrachial cutaneous nerve to repair total brachial plexus avulsion: a preliminary report.

Aim: After brachial plexus injuries, sacrifice of the contralateral C7 (cC7) root from the non-injured side is well tolerated and various schemes to innervate the injured side from the cC7 root have been used. Objective: To demonstrate the surgical outcomes from transferring the cC7 to the affected side via both the ulnar nerve and medial antebrachial cutaneous nerve (MACN).Methods: A retrospective study of 16 adult patients sustaining total brachial plexus avulsion who underwent this procedure. The British Medical Research Council (MRC) grading system and the disabilities of the arm, shoulder, and hand (DASH) questionnaire scoring were used to evaluate the recovery.Results: About 68.75% of the patients achieved functional recovery of elbow flexion to M3 or better and 43.75% achieved motor recovery of wrist and finger flexion to M3 or better. Sensation in the median nerve territory recovered to S2 or better in 68.75%. The DASH scores after surgery were significantly lower than those before surgery.Conclusions: cC7 transfer via both ulnar and MACNs is an effective and safe procedure in patients sustaining total injuries of brachial plexus.

Biological function evaluation and effects of laser micro-pore burn-denatured acellular dermal matrix.

OBJECTIVE: In the field of burns repairs, many problems exist in the shortage of donor skin, the expense of allograft or xenograft skin, temporary substitution and unsatisfactory extremity function after wound healing. Previous studies showed that burn-denatured skin could return to normal dermis formation and function. This study investigates the application of laser micro-pore burn-denatured acellular dermis matrix (DADM) from an escharotomy in the repair of burn wounds and evaluates the biological properties and wound repair effects of DADM in implantation experiments in Kunming mice. METHODS: Specific-pathogen-free (SPF) Kunming mice were used in this study. A deep II° burn wound was created on the dorsum of the mice by an electric heated water bath. The full-thickness wound tissue was harvested. The necrotic tissue and subcutaneous tissue were removed. The denatured dermis was preserved and treated with 0.25% trypsin, 0.5% Triton X-100. The DADM was drilled by laser micro-pore. The biological properties and grafting effects of laser micro-pore burn-DADM were evaluated by morphology, cytokine expression levels and subcutaneous implantation experiments in Kunming mice. RESULTS: We found statistical significance (P<0.05) of the elastic modulus (MPa), maximum load force (N) and contraction measurement (CM) of the laser micro-pore burn-DADM (experimental group) compared to the control group (no laser micro-pore burn-DADM). Cytokine expression level was different in the dermal matrixes harvested at various time points after burn (24h, 48h, 72h and infected wound group). Comparing the dermal matrix from 24h burn tissue to infected wound tissue, the expression level of IL-6, MMP-24, VE-cadherin and VEGF were decreased. We found no inflammatory cells infiltration in the dermal matrix were observed in both experimental and control groups (24h burn group), while the obviously vascular infiltration and fiber fusion were observed in the experimental group after subcutaneous implantation experiments. CONCLUSION: There was better bio-performance, low immunogenicity and better dermal incorporation after treated by laser micro-pore drilling and decellularized deep II° burn-DADM, which may be considered as a better substitute for dermal matrix. Furthermore, the earlier harvested DADM after burn (24h) shows the better transplantation effect.

Distraction Lengthening Following Vascularized Second Toe Transfer for Isolated Middle Finger Reconstruction.

PURPOSE: We report the use of distraction lengthening of the middle phalanx after vascularized second toe transfer for middle finger reconstruction to lengthen the digit to match the index and ring fingers. METHODS: We performed a retrospective review of 3 patients with a mean follow-up of 30 months. RESULTS: A mean increase of 2.0 cm in the length in the digit was achieved. The range of motion at the proximal interphalangeal joint was preserved and bony union was seen at the distraction site in all 3 cases. All patients had an excellent functional and aesthetic outcome. CONCLUSIONS: Distraction lengthening of vascularized toe transfers is a feasible undertaking. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic V.

A novel fluorescent probe for rapid and sensitive detection of hydrogen sulfide in living cells.

A novel fluorescent probe for H2S was developed based on a far-red emitting indole-BODIPY, which was decorated with morpholine and 2,4-dinitrobenzenesulfonyl (DNBS) group. This probe showed rapid response (t1/2=3min), high selectivity and sensitivity for H2S with significant colorimetric and fluorescence OFF-ON signals, which was triggered by cleavage of 2,4-dinitrobenzenesulfonyl group. This probe could quantitatively detect the concentrations of H2S ranging from 0 to 60µM, and the detection of limit was found to be as low as 26nM. Cell imaging results indicated that the probe could detect and visualize H2S in the living cells.

Synthesis and spectroscopic properties of some novel BODIPY dyes.

BODIPY dyes have some unique properties including high fluorescence quantum yield, large extinction coefficiency, narrow absorption and emission band. However, most of BODIPY dyes display short emission wavelength and small Stokes shift, which limits their applications in biosensing and bioimaging in vivo. For bioimaging application, a fluorescent dye with long emission wavelength and large Stokes shift is highly desired. To push the absorption and emission spectrum of BODIPY to red and even far-red region, a COOEt group was introduced to the meso position, and some aromatic group was attached to the 3, 5 position of BODIPY core. The structure of resulting compounds were comfirmed by 1H NMR, 13C NMR and HR-MS. Dye-1 displays a strong UV-Vis absorption band centered at 536 nm and a sharp emission band is located at 592 nm, which is significantly red-shifted (80 nm) compared to ordinary BODIPY analogs. In addition, the meso-COOEt substituted BODIPYs exhibit high quantum yield and red to far-red emission. Notably surprisingly, the meso-COOEt substituted BODIPYs display almost separated UV-Vis absorption and emission spectra with a large Stokes shift (-60 nm). Time-dependent density functional theory calculations were conducted to understand the structure-optical properties relationship, and it was revealed that the large Stokes shift was resulted from the geometric change from the ground state to the first excited singlet state. The spectroscopic properties of these BODIPY dyes display very subtle solvent-dependence effect. Furthermore, BODIPY was tested for its ability of imaging in living cells. The results indicate that Dye-1 is a water-soluble and membrane-permeable probe. Therefore, these BODIPYs are a new family dyes with excellent spectroscopic properties and can be good candidates for bioimaging in living cells.