Kurarinone, a flavonoid from Radix Sophorae Flavescentis, inhibits RANKL-induced osteoclastogenesis in mouse bone marrow-derived monocyte/macrophages.

Inflammation-induced osteoclast proliferation is a crucial contributor to impaired bone metabolism. Kurarinone (KR), a flavonoid extracted from the Radix Sophorae Flavescentis, exhibits notable anti-inflammatory properties. Nevertheless, the precise influence of KR on osteoclast formation remains unclear. This study's objective was to assess the impact of KR on osteoclast activity in vitro and unravel its underlying mechanism. Initially, a target network for KR-osteoclastogenesis-osteoporosis was constructed using network pharmacology. Subsequently, the intersecting targets were identified through the Venny platform and a PPI network was created using Cytoscape 3.9.1. Key targets within the network were identified employing topological algorithms. GO enrichment and KEGG pathway analysis were then performed on these targets to explore their specific functions and pathways. Additionally, molecular docking of potential core targets of KR was conducted, and the results were validated through cell experiments. A total of 83 target genes overlapped between KR and osteoclastogenesis-osteoporosis targets. Enrichment analysis revealed their role in inflammatory response, protein tyrosine kinase activity, osteoclast differentiation, and MAPK and NF-κB signaling pathways. PPI analysis and molecular docking demonstrate that key targets MAPK14 and MAPK8 exhibit more stable binding with KR compared to other proteins. In vitro experiments demonstrate that KR effectively inhibits osteoclast differentiation and bone resorption without cellular toxicity. It suppresses key osteoclast genes (NFATc1, c-Fos, TRAP, MMP9, Ctsk, Atp6v2), hinders IκB-α degradation, and inhibits ERK and JNK phosphorylation, while not affecting p38 phosphorylation. The results indicate that KR may inhibit osteoclast maturation and bone resorption by blocking NF-κB and MAPK signaling pathways, suggesting its potential as a natural therapeutic agent for osteoporosis.

Network Pharmacology and Experimental Validation to Elucidate the Pharmacological Mechanisms of Luteolin Against Chondrocyte Senescence.

BACKGROUND: Luteolin, a flavonoid found in various medicinal plants, has shown promising antioxidant, anti-inflammatory, and anti-aging properties. The cartilaginous endplate (CEP) represents a crucial constituent of the intervertebral disc (IVD), assuming a pivotal responsibility in upholding both the structural and functional stability of the IVD. OBJECTIVE: Exploring the precise mechanism underlying the protective effects of luteolin against senescence and degeneration of endplate chondrocytes (EPCs). METHODS: Relevant targets associated with luteolin and aging were obtained from publicly available databases. To ascertain cellular functions and signaling pathways, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were employed. Core genes were identified through the construction of a protein-protein interaction (PPI) network. Molecular docking (MD) was utilized to assess the binding affinity of luteolin to these core genes. Finally, the impact of luteolin on the senescence and degeneration of EPCs was evaluated in an in vitro cellular senescence model induced by tert-butyl hydroperoxide (TBHP). RESULTS: There are 145 overlapping targets between luteolin and senescence. Analysis using GO revealed that these targets primarily participate in cellular response to oxidative stress and reactive oxygen species. KEGG analysis demonstrated that these markers mainly associate with signaling pathways such as p53 and PI3K-Akt. MD simulations exhibited luteolin's binding affinity to P53, Cyclin-dependent kinase (CDK)2, and CDK4. Cell cycle, cell proliferation, and ß- galactosidase assays confirmed that luteolin mitigated senescence in SW1353 cells. Western blot assays exhibited that luteolin significantly suppressed the expression of Matrix Metallopeptidase (MMP) 13, P53, and P21, while concurrently promoting CDK2, CDK4, and Collagen Type II Alpha 1 (COL2A1) expression. CONCLUSION: In summary, luteolin demonstrated beneficial properties against aging and degeneration in EPCs, offering novel insights to mitigate the progression of intervertebral disc degeneration (IVDD).

Anatomical Study of Cross-Transfer of the Contralateral C7 Nerve Through the Posterior Epidural Pathway of the Cervical Spine for the Treatment of Spastic Paralysis of the Upper Limbs.

BACKGROUND: This study explored the safety and feasibility of surgical treatment of spastic paralysis of the central upper extremity by contralateral cervical 7 nerve transfer via the posterior epidural pathway of the cervical spine. METHODS: Five fresh head and neck anatomical specimens were employed to simulate contralateral cervical 7 nerve transfer through the posterior epidural pathway of the cervical spine. The relevant anatomical landmarks and surrounding anatomical relationships were observed under a microscope, and the relevant anatomical data were measured and analysed. RESULTS: The posterior cervical incision revealed the cervical 6 and 7 laminae, and lateral exploration revealed the cervical 7 nerve. The length of the cervical 7 nerve outside the intervertebral foramen was measured to be 6.4 ± 0.5 cm. The cervical 6 and cervical 7 laminae were opened with a milling cutter. The cervical 7 nerve was extracted from the inner mouth of the intervertebral foramen, and its length was 7.8 ± 0.3 cm. The shortest distance of the cervical 7 nerve transfer via the posterior epidural pathway of the cervical spine was 3.3 ± 0.3 cm. CONCLUSIONS: Cross-transfer surgery of the contralateral cervical 7 nerve via the posterior epidural pathway of the cervical spine can effectively avoid the risk of nerve and blood vessel damage in anterior cervical nerve 7 transfer surgery; the nerve transfer distance is short, and nerve transplantation is not required. This approach may become a safe and effective procedure for the treatment of central upper limb spastic paralysis.

Methods of Immobilization after Achilles Tendon Rupture Repair: A Comparative Study in Rat Model.

OBJECTIVE: The Achilles tendon (AT) is the most frequently ruptured in the human body. Literature describing different immobilization methods' impact on tendon healing after AT repair is lacking. We compare plaster cast, splint, and K-wire to determine which is the most stable and has the fewest complications. METHODS: Sixty rats aged 5-6 months were selected to establish Achilles tendon injury in two hind legs model. After suturing the ends of the AT together with a modified "Kessler" method (Prolene 5-0). The skin incision was interrupted and sutured with 1-0 thread. Rats were divided into three immobilization methods (plaster cast group, splint group, and K-wire group). In plaster cast group, the hind leg was cast with plaster in the extended position of the hip and knee joints, and the ankle joint was at 150°. Splint and K-wire group used splints and 0.8-mm K-wires, separately. The fixed period was 4 weeks. The incidence of stability and complications (death, necrosis of the legs, necrosis of the skin, and incisional infection) were recorded. Differences were detected using the chi-square test. RESULTS: Within 4 weeks observation, K-wires showed better stability (90%) compared with the other two ways (40% in plaster cast group, 65% in splint group; p < 0.05). Rats immobilized with K-wires (10%) suffered significantly lower complications compared with plaster cast and splint group (15%; p < 0.05). CONCLUSION: K-wire has better stability, lower complication rate than other methods. Immobilization with K-wire may be a promising tool in future clinical Achilles tendon rupture applications.

Repair of Finger Pulp Defect and Sensory Reconstruction Using Reverse Homodigital Artery Island Flap With Palmar Cutaneous Branches of the Proper Digital Nerve.

OBJECTIVE: To illustrate the clinical outcomes of the reverse digital proper artery island flap with anastomosing the palmar cutaneous branches of the proper digital nerve for the reconstruction of finger pulp defects. METHODS: From December 2007 to December 2017, a total of 20 patients with finger pulp defects were treated with reverse digital proper artery island flap for innervated construction. Functional outcomes, aesthetic appearance, and complications were evaluated. Functional outcomes were assessed according to range of motion, sensory grade (S0-S4), static 2-point discrimination, Semmes-Weinstein monofilament test, and Cold Intolerance Severity Score. Aesthetic appearance was evaluated according to the Michigan Hand Outcomes Questionnaire. RESULTS: All flaps survived completely without any complications, and all patients were followed up for at least 12 months. The average static 2-point discrimination, Semmes-Weinstein monofilament, and Cold Intolerance Severity Score results of the injured fingers were 6.35 mm (range, 5-8 mm), 3.64 (range, 2.83-4.17), and 19 (range, 8-24), respectively. All patients achieved recovery in sensation from S3+ to S4. The active ranges of motion of the metacarpophalangeal, proximal interphalangeal, and distal interphalangeal joints of the affected fingers were satisfactory. Based on the Michigan Hand Outcomes Questionnaire, 11 patients were strongly satisfied, and 9 were satisfied with the appearance of the injured finger. CONCLUSIONS: The reverse digital proper artery island flap with anastomosing the palmar cutaneous branches of the proper digital nerve is an effective and reliable alternative for the reconstruction of finger pulp defect. In the recovery of sensation, this flap leads to satisfactory effects.

Comparison of Treatment Methods of Thumb-Tip Defects With Phalangeal Bone Exposure: Modified Heterodigital Neurovascular Island Flap Versus Free Lateral Great Toe Flap.

PURPOSE: Modified heterodigital neurovascular island flaps and free lateral great toe flaps are dependable methods for treating thumb-tip defects with phalangeal bone exposure. We retrospectively analyzed and compared the details and results of the two methods. METHODS: This retrospective study included 25 patients with thumb injuries with phalangeal bone exposure treated between 2018 and 2021. Patients were categorized as per the following surgical methods: (1) modified heterodigital neurovascular island flap (12 patients, finger flap group) and (2) free lateral great toe flap (13 patients, toe flap group). The Michigan Hand Outcome Questionnaire, aesthetic appearance, Vancouver Scar Scale, Cold Intolerance Severity Score, static 2-point discrimination, Semmes-Weinstein monofilament, and range of motion of the metacarpophalangeal joint of the injured thumb were evaluated and compared. In addition, operation time, hospital stay, return-to-work time, and complications were recorded and compared. RESULTS: In both groups, the defect was successfully repaired, with no cases of complete necrosis. The 2 groups had similar mean scores in static 2-point discrimination, Semmes-Weinstein monofilament, range of motion, and Michigan Hand Outcome Questionnaire scores. The aesthetic appearance, scarring, and cold tolerance of the toe flap group were better than the finger flap group. The operation time, hospital stay, and return-to-work time in the finger flap group were shorter than the toe flap group. The finger flap group had 2 complications-a superficial infection and 1 case of partial flap necrosis. The toe flap group had 3 complications-a superficial infection, 1 case each of partial flap necrosis, and partial skin graft loss. CONCLUSION: Both treatments can achieve satisfactory results; however, they each have advantages and disadvantages. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV.

Reconstruction of the central slip insertion of the extensor tendon with the partial slip of the flexor digitorum superficialis tendon.

INTRODUCTION: To introduce the surgical approach and clinical effect of transferring the partial slips of the flexor digitorum superficialis (FDS) tendon to reconstruct the insertion of the central slip of the extensor tendon (CSET) through an established bone tunnel (BT). MATERIALS AND METHODS: From April 2019 to March 2021, nine patients (six males and three females) with the CSET insertion rupture or defect were admitted to the institution and the CSET insertion was reconstructed with partial tendon slips on both sides of the FDS. The active range of motion of the interphalangeal joint of the affected finger was measured by a goniometer, the degree of pain was evaluated by visual analogue scale (VAS), and the grip strength of the affected limb was measured by an electronic hand dynamometer. RESULTS: The average postoperative follow-up was 12 months. No complications occurred. At the last follow-up, six of the patients were very satisfied and three were satisfied with their recovery. CONCLUSION: The reconstruction of the CSET insertion by transferring the partial tendon slips of the FDS seem to be safe and feasible with minimal invasion to the donor tendon. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV.

Reverse digital artery island flap with versus without sensory nerve coaptation for finger pulp reconstruction.

PURPOSE: Whether an innervated reverse digital artery island flap is superior to a non-innervated reverse digital artery island flap still remains controversial. We aimed to compare the clinical outcomes of the two flaps in repairing finger pulp soft tissue defects. METHODS: Medical records of patients who underwent finger pulp reconstruction between January 2007 and December 2017 were evaluated retrospectively. A total of 45 patients were included. Twenty underwent sensory nerve reconstruction with cutaneous branches of the proper digital nerve, and 25 underwent the surgery without sensory nerve reconstruction. Surgical results, complications and sensory function were collected for analysis. Sensory function was assessed by static two-point discrimination and the modified sensory evaluation standard of British Medical Research Council. RESULTS: The average operation time of innervated flaps was 23 min longer than non-innervated flaps. All 45 flaps survived completely. There was no significant difference in complications between groups. The average follow-up was 22 months. At the final follow-up, five non-innervated flaps had no recovery of static two-point discrimination. The average static two-point discrimination of the remaining 20 non-innervated flaps was larger than that of innervated flaps. Innervated flaps consistently achieved higher sensory function grades according to the modified sensory evaluation standard of British Medical Research Council. CONCLUSION: An innervated reverse digital artery island flap can achieve better sensory function recovery in a shorter time. This procedure did not increase the incidence of complications, although it extended the operation time. It has proven to be a good technique for finger pulp reconstruction.

Efficacy analysis of three kinds of surgery for trigger thumb.

PURPOSE: To study the efficacy of three kinds of surgery for trigger thumb. METHODS: A total of 60 cases of trigger thumb (Quinnell Grade IV) were randomly divided into three groups. The A1 pulley was disconnected at the middle in Group A, at the extreme radial side in Group B, excised in Group C. The following indicators were recorded pre-operatively (D0), and at one (D1), three (D3), seven (D7), 14 (D14), and 28 (D28) days post-operatively: 1. the pain visual analogue score (VAS) when flexing the affected thumb; 2. range of motion (ROM) of the interphalangeal joint with pain tolerance; 3. the time of pain disappearance when flexing the affected thumb. RESULTS: The differences of VAS and ROM between D1 and D0, D3 and D1, D7 and D3, D14 and D7, D28 and D14 were statistically significant (P < 0.05). There was no significant difference in changes of VAS (or ROM) at D1 or D28 in contrast to D0 among the three groups. The differences of VAS (or ROM) changes at D3, D7, and D14 in contrast to D0 among the three groups were statistically significant (P < 0.05). The difference of the time when the pain disappearing in the normal range of motion among the three groups were statistically significant (P < 0.05). CONCLUSION: Disconnecting the A1-pulley at the extreme radial side is better than another two methods for treating the trigger thumb (Quinnell Grade IV). It has been shown to effectively accelerate postoperative pain relief and functional recovery. TRIAL REGISTRATION: Clinical trial registry number: ChiCTR2100051193.

Coverage of Big Toe Defects After Wraparound Flap Transfer With a Second-Toe Medial-Side Adjacent Toe Flap.

PURPOSE: In finger reconstruction, big-toe wraparound flap (WAF) transfer provides excellent results. However, difficulty in healing and impaired function at the donor site are common. We aimed to explore an ideal method to address these complications. METHODS: This retrospective study involved 22 patients who were treated with big toe WAF transfer for finger reconstruction between 2016 and 2020. Patients were categorized into cohorts by donor site repair method: second-toe medial-side adjacent toe flap and skin graft (cohort 1) and skin graft alone (cohort 2). Functional outcomes, aesthetic appearance, and complications at the donor site were compared. Functional outcomes were assessed according to the American Orthopaedic Foot and Ankle Society (AOFAS) for hallux metatarsophalangeal-interphalangeal score, Foot Function Index-Verbal Rating Scales (FFI-5 pt), and visual analog scale for pain. Aesthetic appearance was evaluated according to the adjusted question 28 in the Michigan Hand Outcome Questionnaire. RESULTS: The mean pain scores in AOFAS and FFI-5 pt were 38.00 ± 4.22 and 3.75 ± 2.37, and 32.50 ± 4.52 and 6.60 ± 2.14 in cohorts 1 and 2, respectively, which showed no significant differences. The method in cohort 1 can reduce the level of pain. This was further confirmed by visual analog scale scores of 3.40 ± 0.84 and 6.42 ± 7.93 in cohorts 1 and 2, respectively. The mean functional scores in AOFAS and FFI-5 pt were 38.40 ± 2.37 and 1.25 ± 1.62, and 37.92 ± 2.15 and 1.56 ± 2.11 in cohorts 1 and 2, respectively, which showed no significant differences. Eight patients developed complications: 1 patient (1/10 [10%]) in cohort 1 developed a superficial infection, and in cohort 2, 7 patients (7/12, 58.30%) developed complications, including 2 short-term complications with partial necrosis and 1 delayed healing. Long-term complications included the following: scar discomfort (2 cases), pain discomfort (1 case), and skin ulceration due to repeated wear and tear (1 case). Cohort 2 had significantly more complications than cohort 1. CONCLUSIONS: Second-toe medial-side adjacent toe flap combined with skin graft had better aesthetic appearance, less complications, and less pain compared with skin graft alone. Hence, it can be a reliable technique for repairing the donor site after big-toe WAF transfer.

Effects of Cartilage Progenitor Cells, Bone Marrow Mesenchymal Stem Cells and Chondrocytes on Cartilage Repair as Seed Cells: An in vitro Study.

Purpose: To determine the effects of cartilage progenitor cells, bone marrow mesenchymal stem cells and chondrocytes on cartilage repair as seed cells. Methods: Porcine cartilage progenitor cells (CPCs), bone marrow mesenchymal stem cells (BMSCs) and chondrocytes (CCs) were obtained from the femoropatellar joints of young pigs, and seeded in agarose gel as a graft. During the 28-day culture, proliferation ability was measured by MTT assay, and gene expression of Collagen I, Collagen II, Aggrecan and SOX 9 were measured by qPCR. Qualitative and quantitative analysis of collagen, glycosaminoglycan and DNA were appraised by immunohistochemical staining and biochemical assay, and integration strength was analyzed by push-out tests. Results: After 28-day culture, proliferation ability of CPCs and BMSCs was higher than CCs. Collagen, glycosaminoglycan, DNA content and chondrocyte-related genes expression in the cartilage progenitor cells seeded gel were significantly higher than the other two gels. Integration strength in the cartilage progenitor cells seeded gel was also higher compared with the other two gels. Conclusion: Compared with CCs and BMSCs, CPCs in vitro have dominance in the ability of cell proliferation and differentiation as seed cells in tissue engineering.

Comparison of different segments in the fixation of thoracolumbar fractures: a Bayesian network meta-analysis.

BACKGROUND: Posterior internal fixation (PIF) is commonly used in the treatment of thoracolumbar fracture (TLF), but there is still no standard for the number of fixed segments. The objective of this meta-analysis was to evaluate the efficacy and safety of short segment (SS), intermediate segment (IS) and long segment (LS) in the fixation of TLF. METHODS: Two authors independently searched through PubMed, Embase, Cochrane Library and Web of Science for studies of thoracolumbar fracture treated by posterior internal fixation, which were published until the end of April 2021. The Aggregate Data Drug Information System (ADDIS) software was used for data evaluation according to the Markov chain Monte Carlo (MCMC) method based on the Bayesian theorem. RESULTS: Nineteen trials evaluating a total of 970 patients were enrolled in these studies, of which 340 in the SS group, 429 in the IS group and 201 in the LS group. For anterior vertebral height ratio (AVHR), IS had the highest AVHR, LS had the second highest AVHR. IS also ranked first in reducing visual analogue scale (VAS), SS ranked second. For sagittal Cobb's angle (SCA), LS had the lowest SCA and IS had the second lowest SCA. In terms of adverse events, IS had the lowest implant failure rate and LS had the second lowest implant failure rate. CONCLUSIONS: IS may be the most desirable treatment option for TLF in reducing SCA, implant failure rate, VAS, and improving AVHR. However, more randomized controlled trials are needed to verify these results.

Carpal tunnel syndrome caused by tophi deposited under the epineurium of the median nerve: A case report.

Introduction: Usually caused by compression of the wrist's median nerve, carpal tunnel syndrome (CTS) is one of the most common types of peripheral neuropathy. Tophi deposited under the epineurium of the median nerve compress the median nerve, leading to CTS, which is very rare. Case presentation: We report a 64-year-old man with a history of tophaceous gout who presented with typical CTS symptoms and was admitted to our hospital. A physical examination revealed swelling over the right volar aspect of the carpal region, and he was unable to flex due to subcutaneous rigidity. Tinel's sign and Phalen's maneuver were positive. Electrophysiological studies confirmed the diagnosis of CTS. A carpal tunnel release and surgery to remove the gouty tophus of the right wrist were performed when serum uric acid levels were within normal limits (5.8 mg/dl). During the operation, tophi deposited under the epineurium of the median nerve were found, and the tophi were completely removed. Operative findings confirmed the diagnosis of CTS due to gout. The patient recovered uneventfully without signs of recurrence of gout and CTS symptoms during a 1-year follow-up period. Conclusion: A gouty tophus is an uncommon cause of CTS, and CTS may be caused by gouty tophi if there is evidence of extrinsic compression of the median nerve or symptoms emanating from the carpal tunnel.