Comparing the Outcomes of Suture Anchor Repair and Rein-Type Capsular Suture for Triangular Fibrocartilage Complex Foveal Tears With a Minimum 2-Year Follow-Up.

PURPOSE: Recent biomechanical studies have highlighted the importance of foveal reinsertion when repairing triangular fibrocartilage complex (TFCC) injury with foveal tears. However, clinical studies comparing different repair techniques are scarce. We compared the clinical outcomes of suture anchor repair and rein-type capsular suture in patients with TFCC palmer 1B foveal tears with a minimum of 2-year follow-up. METHODS: This was a single-surgeon, single-center, retrospective, comparative study. We included patients who underwent TFCC repair surgery due to a foveal tear from December 2013 to October 2018 with a minimum follow-up of 24 months. Postoperative Quick Disabilities of Arm, Shoulder, and Hand (QuickDASH) score, Modified Mayo Wrist Score, visual analogue scale for pain, wrist range of motion, and grip strength were compared. We also measured the maximal ulnar head displacement with dynamic ultrasound to quantify distal radioulnar joint stability. RESULTS: In total, 103 patients were in the suture anchor group (group A) and 84 patients in the rein-type capsular suture group (group B). The mean follow-up time exceeded three years for both groups. There was a minimal difference regarding QuickDASH score, visual analogue scale for pain, and grip strength ratio between the two groups. The rein-type group had significantly better Modified Mayo Wrist Score. The suture anchor group showed better distal radioulnar joint stability with dynamic ultrasound, but was more limited in ulnar deviation. However, these differences are most likely clinically insignificant. CONCLUSIONS: Both suture anchor repair and rein-type capsular suture yielded satisfactory results for TFCC 1B foveal tear in a minimum of 2-year follow-up. The functional scores were similar, and no major complications or recurrent instability were noted in either group. TYPE OF STUDY/LEVEL OF EVIDENCE: Retrospective Therapeutic Comparative Investigation IV.

Mitoquinone protects against acetaminophen-induced liver injury in an FSP1-dependent and GPX4-independent manner.

Mitochondrial oxidative stress has been a crucial mediator in acetaminophen (APAP)-induced hepatotoxicity. MitoQ, an analog of coenzyme Q10, is targeted towards mitochondria and acts as a potent antioxidant. This study aimed to explore the effect of MitoQ on APAP-induced liver injury and its possible mechanisms. To investigate this, CD-1 mice and AML-12 cells were treated with APAP. Hepatic MDA and 4-HNE, two markers of lipid peroxidation (LPO), were elevated as early as 2 h after APAP. Oxidized lipids were rapidly upregulated in APAP-exposed AML-12 cells. Hepatocyte death and mitochondrial ultrastructure alterations were observed in APAP-induced acute liver injury. The in vitro experiments showed that mitochondrial membrane potentials and OXPHOS subunits were downregulated in APAP-exposed hepatocytes. MtROS and oxidized lipids were elevated in APAP-exposed hepatocytes. We discovered that APAP-induced hepatocyte death and liver injury were ameliorated by attenuation of protein nitration and LPO in MitoQ-pretreated mice. Mechanistically, knockdown of GPX4, a key enzyme for LPO defense systems, exacerbated APAP-induced oxidized lipids, but did not influence the protective effect of MitoQ on APAP-induced LPO and hepatocyte death. Whereas knockdown of FSP1, another key enzyme for LPO defense systems, had little effect on APAP-induced lipid oxidation but partially weakened the protection of MitoQ on APAP-induced LPO and hepatocyte death. These results suggest that MitoQ may alleviate APAP-evoked hepatotoxicity by eliminating protein nitration and suppressing hepatic LPO. MitoQ prevents APAP-induced liver injury partially dependent of FSP1 and independent of GPX4.

Chinese herbal medicine compound of flavonoids adjunctive treatment for oral cancer.

Oral cancer is a prevalent global issue, with oral squamous cell carcinoma constituting the majority of cases. Standard treatments like surgery, radiotherapy, and chemotherapy are available but may have adverse effects. Molecular gene therapy, focusing on genetic mutations linked to oral cancer, presents a promising alternative.In this study, we evaluated 27 chemotherapeutic drugs and 63 Chinese herbal medicines for their effectiveness, categorized them by their cellular mechanisms, and identified potential adjuvant therapy candidates for oral cancer. Our findings highlight the impact of natural flavonoids on oral cancer cells, inducing apoptosis, and confirming their potential in molecular genetic analysis. In conclusion, the natural compounds present in Chinese herbal medicine, particularly flavonoids, offer a promising avenue to target specific genetic mutations in oral cancer cells. This approach may reduce the risks associated with oral cancer treatment and pave the way for innovative adjuvant therapies.

Radial distraction may reduce the incidence of ulnar-sided wrist pain in ulna-plus morphology intraoperatively following distal radius fractures fixation.

INTRODUCTION: Fixed-angle plate fixation can be an effective treatment for distal radius fractures (DRFs). However, patients with existing ulnar positive variance might be at risk of developing symptoms of ulnar-sided wrist pain (USWP). Ulnar shortening osteotomy (USO) is one of the main treatment options for USWP. We hypothesized that a limited radial distraction at the fracture site at the time of surgery for DRF would be functionally equivalent to an indirect USO and that if this were done in a patient with an ulnar plus morphology it could potentially decrease the risk of USWP. METHODS: This retrospective study was conducted at a single institution and all the surgeries were performed by single surgeon. A total of 136 patients (92 women and 44 men) with a mean age of 55 years were enrolled with 57 patients in the distraction group (from 2014 to 2017) and 79 patients (from 2011 to 2013) in the non-distraction group. Patients were assessed USWP. Functional outcomes were assessed using the Disabilities of the Arm, Shoulder and Hand (DASH) questionnaire, Visual Analogue Scale (VAS) for pain, grip strength, and range of motion for the wrist. RESULTS: The mean follow-up was 37.9 months (range, 28-61 months). The radiographs at postoperative 2-year follow-ups showed the mean ulnar positive variance was 1.3 mm (range, 1-2 mm) in the distraction group and 3.5 mm (range, 2-5 mm) in the non-distraction group. The average of the distraction length was 2.32 mm (range, 2-3 mm). At the 2-year follow-ups, USWP presented in 7% (four patients) in the distraction group, which was significantly less than the incidence of 28% (22 patients) in the non-distraction group. The distraction group exhibited significantly better DASH scores and grip strength and less subsequent ulnar-shortening osteotomy for ulnar-sided wrist pain. CONCLUSIONS: The radial distraction procedure performed during DRFs fixation could possibly reduce the occurrence of postoperative USWP and improve the functional outcomes. LEVEL OF EVIDENCE: Level III, Therapeutic.

Arthroscopic-assisted radiocarpal ligaments tensioning for dynamic radiocarpal instability.

BACKGROUND: Dynamic radiocarpal instability is one of the causes of post-trauma radial-sided wrist pain. It is not easy to diagnose and may possibly be overlooked. The key ligaments responsible for dynamic radiocarpal instability are the radioscaphocapitate (RSC) and long radiolunate (LRL) ligaments. Tensioning of these 2 ligaments could be a method of treatment for dynamic carpal instability. We proposed a method for arthroscopic thermal shrinkage of these 2 ligaments, and for setting a landmark arthroscopically to facilitate identification of these 2 ligaments during the combined open suture tensioning procedure. METHODS: Between January 2016 and May 2020, 12 patients treated with this method were enrolled. The mean age was 33.3 years (range, 18-57 years), and the mean duration from injury to operation was 7.8 months (range, 3-25 months). The diagnosis was mainly depended on the physical examinations and confirmed under arthroscopy. The mean follow-up was 17.7 months (range, 12-26 months). RESULTS: All the patients had marked improvement of pain, grip strength, the Disabilities of the Arm, Shoulder and Hand questionnaire (DASH), and the radiocarpal stability. The wrist range of motion showed significant decrease around 5o in both flexion and extension and around 4o in the ulnar deviation at the final follow-ups. All patients were able to return to their previous full level of work and activities. CONCLUSIONS: We conclude that arthroscopic thermal shrinkage combined with open suture tensioning can be effective in treating dynamic carpal instability, while the arthroscopic-assisted landmark setting can help identify the accurate location of the RSC and LRL ligaments without dissecting too much soft tissue.

Comparing radial lengthening osteotomy with ulnar shortening osteotomy to treat ulnar impaction syndrome after distal radius fracture malunion.

INTRODUCTION: Distal radius mal-unions often cause radius shortening and ulnar impaction syndrome. The modern treatments of ulnar impaction syndrome following distal radius mal-union are ulnar shortening osteotomy (USO) and distal radius lengthening osteotomy (DRLO). However, there are few studies to compare long-term outcomes of these two treatments. This study compares isolated USO to DRLO for the treatment of ulnar impaction syndrome following distal radius mal-union. MATERIALS AND METHODS: We retrospectively reviewed 68 patients with extra-articular distal radius mal-unions treated by isolated USO in 36 patients and DRLO in 32 patients. Pain visual analog scale (VAS), wrist motion, grip strength, radiographic parameters including sigmoid inclination, DASH score, and perioperative complications were analyzed. Mean follow-up was 62.6 months. RESULTS: The postoperative VAS scores for pain on exertion were less in the DRLO group than the USO group (1.2 vs. 2.8, p = 0.02). The DASH scores were 16.7 and 29.8 in the DRLO and USO groups, respectively (p = 0.02). The reduction of pain and improvement of function showed significantly better in the DRLO group. The mean operative time was shorter in the USO group. Most of the sigmoid inclinations were changed in DRLO. There were two re-operations following USO for painful nonunion and two patients had subsequent DRUJ osteoarthritis at the last follow-up. CONCLUSION: Although both treatments improved range of motion, grip strength, and VAS for pain, DRLO was found in better reduction of pain and improvement of function. USO is a simpler procedure with a shorter operative time but it has an increased potential to cause subsequent osteoarthritis of the DRUJ as its incongruity of DRUJ after USO especially in reverted inclination. DRLO can be a preferred method for treating USWP in relevant distal radial mal-union.

Long-term radiographic outcomes and functional evaluation of ulnar shortening osteotomy in patients with ulnar impaction syndrome and reverse oblique sigmoid notch: a retrospective case series study.

BACKGROUND: Ulnar shortening osteotomy (USO) is an effective treatment for ulnar impaction syndrome. However, there have been reports of osteoarthritis (OA) at the distal radioulnar joint (DRUJ) when USO was performed on patients with a reverse oblique sigmoid notch. This study aimed to evaluate the radiographic and functional outcomes following USO in patients with a reverse oblique sigmoid notch. METHODS: We retrospectively reviewed patients having a reverse oblique sigmoid notch who underwent USO for ulnar impaction syndrome between 2002 and 2013. We evaluated radiographic changes of the DRUJ and functional outcomes of patients. RESULTS: We enrolled 22 patients (22 wrists) with an average age of 49.6 years and a mean follow-up of 93.2 (range, 36-179; standard deviation [SD], 38.2) months. We found that there were changes in the inclination angle of the sigmoid notch, from an average reverse oblique of 14.9o (range, 11o-23o; SD, 3.4o) preoperatively to a more parallel 5.1o (range, 0o-11o; SD, 3.2o) at the final follow-up. The functional results at the final follow-up were good, with a mean visual analogue scale for pain of 0.2 (range, 0-1; SD, 0.4) at rest and 1.3 (range, 0-3; SD, 0.9) during activity, QuickDASH of 15.1 (range, 2.3-34.1; SD, 8.8), and modified Mayo Wrist Score of 91.6 (range, 70-100; SD, 6.4). Seven wrists (31.8%) had changes compatible with OA, but the wrists did not exhibit a significantly worse function when compared to wrists without OA changes, except for supination motion and grip strength. CONCLUSIONS: For patients with a reverse oblique sigmoid inclination following USO, we observed that the inclination angle had a tendency to become parallel and some patients developed OA at the DRUJ. However, long-term functional outcomes could still be good. The reverse oblique sigmoid inclination does not seem to be an absolute contraindication for USO.

Arthroscopic realignment and osteosynthesis of unstable scaphoid nonunion with cancellous bone graft from the ipsilateral radius.

PURPOSE: The treatment of delayed union and established nonunion of the scaphoid using a volar approach with impaction of bone graft, either a cancellous or cortico-cancellous wedge graft, for osteosynthesis and maintenance of reduction. With the advancement of instruments and techniques of wrist arthroscopy, wider indications for wrist problems can be solved by this minimally invasive technique. We report our results of arthroscopic reduction, cancellous bone grafting to the regional distal radius, and headless screw fixation for the treatment of scaphoid nonunion, even with humpback deformity. METHODS: Between August 2014 and February 2018, 41 patients (42 wrists) with unstable scaphoid nonunion received arthroscopic surgery. The mean follow-up was 38.1 months (range 24-70 months). We evaluated the results with a function questionnaire and clinical outcomes based on the visual analog scale (VAS) pain score, range of motion and grip strength, and radiologic measurements. RESULTS: The union rate was 92.6% (38/41 patients) and union time was 4.6 months. Patients regained almost a full range of motion compared with the contralateral wrist. The post-op Quick DASH, Mayo wrist score, and VAS pain score all had significant improvement, with p < 0.05. The scapholunate angle showed significant correction from pre-op 68.0° to post-op 58.3°. The average VAS satisfaction score at final follow-up was 8.7. CONCLUSION: Arthroscopic realignment and osteosynthesis for the treatment of unstable scaphoid nonunion with ipsilateral radius bone graft, even with humpback deformity, can achieve a high union rate, good radiological correction, and good functional recovery.

Cysteine-Aminoethylation-Assisted Chemical Ubiquitination of Recombinant Histones.

Histone ubiquitination affects the structure and function of nucleosomes through tightly regulated dynamic reversible processes. The efficient preparation of ubiquitinated histones and their analogs is important for biochemical and biophysical studies on histone ubiquitination. Here, we report the CAACU (cysteine-aminoethylation assisted chemical ubiquitination) strategy for the efficient synthesis of ubiquitinated histone analogs. The key step in the CAACU strategy is the installation of an N-alkylated 2-bromoethylamine derivative into a recombinant histone through cysteine aminoethylation, followed by native chemical ligation assisted by Seitz's auxiliary to produce mono- and diubiquitin (Ub) and small ubiquitin-like modifier (SUMO) modified histone analogs. This approach enables the rapid production of modified histones from recombinant proteins at about 1.5-6 mg/L expression. The thioether-containing isopeptide bonds in the products are chemically stable and bear only one atomic substitution in the structure, compared to their native counterparts. The ubiquitinated histone analogs prepared by CAACU can be readily reconstituted into nucleosomes and selectively recognized by relevant interacting proteins. The thioether-containing isopeptide bonds can also be recognized and hydrolyzed by deubiquitinases (DUBs). Cryo-electron microscopy (cryo-EM) of the nucleosome containing H2BKC34Ub indicated that the obtained CAACU histones were of good quality for structural studies. Collectively, this work exemplifies the utility of the CAACU strategy for the simple and efficient production of homogeneous ubiquitinated and SUMOylated histones for biochemical and biophysical studies.

Segmentation of pulmonary vascular tree by incorporating vessel enhancement filter and variational region-growing.

BACKGROUND: Automatic segmentation of pulmonary vascular tree in the thoracic computed tomography (CT) image is a promising but challenging task with great clinical potential values. It is difficult to segment the whole vascular tree in reasonable time and acceptable accuracy. OBJECTIVE: To develop a novel pulmonary vessel segmentation approach by incorporating vessel enhancement filters and the anisotropic diffusion filter with the variational region growing. METHODS: First, the airway wall from the lung lobes is eliminated from CT images by using multi-scale morphological operations. Second, a Hessian-based multi-scale vesselness filter and medialness filter are applied to detect and enhance the potential vessel. Third, an anisotropic diffusion filter is used to remove noise and enhance the tube-like structures in CT images. Last, the vascular tree is segmented by applying variational region growing algorithm. RESULTS: Applying to the CT images collected from the entire dataset of VESSEL12 challenge, we achieved an average sensitivity of 92.9%, specificity of 91.6% and the area under the ROC curve of AUC = 0.972. CONCLUSIONS: This study demonstrated feasibility of segmenting the pulmonary vessel effectively by incorporating vessel enhancement filters and the anisotropic diffusion filter with the variational region growing algorithm. Our method cannot only segment both large and peripheral vessels, but also distinguish the vessels from the adjacent tissues, especially the airway walls.

KAHA Ligation at Serine.

Oxazetidine assisted KAHA ligation was developed by the Bode group as an efficient peptide segment ligation strategy at native serine residues. This milestone achievement should enable the chemical synthesis of difficult-to-prepare proteins for biological studies.

Synthesis of l- and d-Ubiquitin by One-Pot Ligation and Metal-Free Desulfurization.

Native chemical ligation combined with desulfurization has become a powerful strategy for the chemical synthesis of proteins. Here we describe the use of a new thiol additive, methyl thioglycolate, to accomplish one-pot native chemical ligation and metal-free desulfurization for chemical protein synthesis. This one-pot strategy was used to prepare ubiquitin from two or three peptide segments. Circular dichroism spectroscopy and racemic protein X-ray crystallography confirmed the correct folding of ubiquitin. Our results demonstrate that proteins synthesized chemically by streamlined 9-fluorenylmethoxycarbonyl (Fmoc) solid-phase peptide synthesis coupled with a one-pot ligation-desulfurization strategy can supply useful molecules with sufficient purity for crystallographic studies.

Hmb(off/on) as a switchable thiol protecting group for native chemical ligation.

A new thiol protecting group Hmb(off/on) is described, which has a switchable activity that may be useful in the chemical synthesis of proteins. When placed on the side chain of Cys, Cys(Hmb(off)) is stable to trifluoroacetic acid (TFA) in the process of solid-phase peptide synthesis. When Cys(Hmb(off)) is treated with neutral aqueous buffers, it is cleanly converted to acid-labile Cys(Hmb(on)), which can later be fully deprotected by TFA to generate free Cys. The utility of Cys(Hmb(off/on)) is demonstrated by the chemical synthesis of an erythropoietin segment, EPO[Cys(98)-Arg(166)]-OH through native chemical ligation.

Total synthesis of mambalgin-1/2/3 by two-segment hydrazide-based native chemical ligation.

Mambalgins are a class of 57-residue polypeptide toxins isolated from the venom of the African mamba. They exhibit potent analgesic effects by inhibiting the acid-sensing ion channels. Classified as members of the family of three-finger toxins, mambalgins contain four pairs of disulfide bridges that help to stabilize the three-finger scaffold. Here, we report the chemical synthesis of functional mambalgin-1/2/3 by using one-step two-segment hydrazide-based native chemical ligation. The two-segment ligation approach reported here may enable efficient production of mambalgin toxins. These synthetic mambalgins are useful compounds for development of diagnostic or therapeutic reagents. Copyright © 2016 European Peptide Society and John Wiley & Sons, Ltd.

Accelerated Fmoc solid-phase synthesis of peptides with aggregation-disrupting backbones.

In this work, we describe an accelerated solid-phase synthetic protocol for ordinary or difficult peptides involving air-bath heating and amide protection. For the Hmsb-based backbone amide protection, an optimized acyl shift condition using 1,4-dioxane was discovered. The efficiency and robustness of the protocol was validated in the course of preparation of classical difficult peptides and ubiquitin protein segments.

Development of new thioester equivalents for protein chemical synthesis.

The chemical synthesis of proteins provides synthetic chemists with an interesting challenge and supports biological research through the generation of proteins that are not produced naturally. Although it offers advantages, studies of solid phase peptide synthesis have established limits for this technique: researchers can only prepare peptides up to 50 amino acids in length in sufficient yields and purity. Therefore, researchers have developed techniques to condense peptide segments to build longer polypeptide chains. The method of choice for chemical synthesis of these longer polypeptides is convergent condensation of unprotected protein fragments by the native chemical ligation reaction in aqueous buffer. As researchers apply this strategy to increasingly difficult protein targets, they have needed to overcome diverse problems such as the requirement for a thiol-containing amino acid residue at the ligation site, the difficulty in synthesizing thioester intermediates under mild conditions, and the challenge of condensing multiple peptide segments with higher efficiency. In this Account, we describe our research toward the development of new thioester equivalents for protein chemical synthesis. We have focused on a simple idea of finding new chemistry to selectively convert a relatively "low-energy" acyl group such as an ester or amide to a thioester under mild conditions. We have learned that this seemingly unfavorable acyl substitution process can occur by the coupling of the ester or amide with another energetically favorable reaction, such as the irreversible hydrolysis of an enamine or condensation of a hydrazide with nitrous acid. Using this strategy, we have developed several new thioester equivalents that we can use for the condensation of protein segments. These new thioester equivalents not only improve the efficiency for the preparation of the intermediates needed for protein chemical synthesis but also allow for the design of new convergent routes for the condensation of multiple protein fragments.

Irreversible site-specific hydrazinolysis of proteins by use of sortase.

Sortase-mediated hydrazinolysis of proteins with hydrazine or its derivatives was developed for the production of recombinant protein hydrazides. This process provides an alternative approach for protein semisynthesis through the use of recombinant protein hydrazides as thioester surrogates. It also provides an alternative method for C-terminal modification of proteins with functional units as well as for the preparation of C-to-C fusion proteins.

Research and Development of a 3D-Printed Dynamic Finger Flexion Orthosis for Finger Extension Stiffness-A Preliminary Study.

Finger extension stiffness is a common post-traumatic complication that results in the hand's functional impairment. In clinical practice, a dynamic splint enables the patient to stretch the affected finger independently. However, current dynamic splints have drawbacks, such as limited stretching efficacy, and interfere with the hand's functional activities. Therefore, this study aimed to develop a dynamic finger flexion orthosis capable of stretching each finger joint using additive manufacturing (AM) technology, thereby enabling hand functional activity, and analyze the clinical improvement in the range of motion (ROM). One subject with a hand fracture was recruited while undergoing a 7-week home-based rehabilitation program for the orthosis. The outcome measurements included the total active motion (TAM), the tip-to-finger distance (TPD), and the score on the Disability of Arm, Shoulder, and Hand (DASH) questionnaire. The results show that the TAM of the participant's fingers increased by 72.7 degrees on average, the TPD decreased by 3.5 cm on average, and the DASH score decreased to 9.5 points. The 7-week home-based rehabilitation program for the orthosis resulted in a 53.6% increase in the TAM on average. The developed orthosis improved hand function and enabled a more complete ROM in finger flexion.

Arthroscopic debridement, synovectomy, and thermal shrinkage for basal joint arthritis.

BACKGROUND: Ligamentous laxity, cartilage wear, and diffuse synovitis are frequently seen in thumb basal joint arthritis. Although these degenerative changes may be mild for the majority, they have the potential to cause discomfort during movement and compromised hand function. This study assesses the long-term outcomes of arthroscopic debridement, synovectomy, and thermal shrinkage in managing early-stage basal joint arthritis. METHODS: We retrospectively reviewed patients with basal joint arthritis who underwent arthroscopic debridement, synovectomy, and thermal shrinkage between November 2010 and January 2021 by a single surgeon at our medical institute. We assessed functional outcomes, thumb range of motion, perioperative nonsteroidal anti-inflammatory drug (NSAID) use, return to work and satisfaction level. RESULTS: A total of 12 patients (13 hands), with a mean follow-up of 72 months, were included in this study. Significant improvements were observed in pain scores and functional outcomes, along with a reduction in postoperative NSAID use. Patients also reported a relatively quick return to work and a high satisfaction level. CONCLUSION: The study highlights the benefits of arthroscopic intervention, providing a minimally invasive approach with favorable long-term outcomes for patients with symptomatic basal joint arthritis.