USP6 and circCYFIP2 target oncoprotein GOLPH3 for deubiquitination and induce platinum resistance in colon cancer.

GOLPH3 has been identified as an oncoprotein, playing a crucial role on progression and chemoresistancein of colon adenocarcinoma (COAD). However, it is still unclear the regulation of GOLPH3 expression at protein level. We discovered ubiquitin-specific proteases 6 (USP6) directly regulated the deubiquitination of the GOLPH3 protein and enhanced its stability in COAD. Overexpression of USP6 promoted COAD cell viability, inhibited apoptosis, and accelerated the growth of transplanted tumors growth in vitro and in vivo by deubiquitinating GOLPH3. Additionally, circCYFIP2 showed high expression levels in DDP-resistant colon cancer cells, promoting the cell proliferation. Mechanically, circCYFIP2 binds to both GOLPH3 protein and USP6, strengthening the interaction between GOLPH3 and USP6, and consequently induced DDP resistance in vitro and in vivo. In conclusion, USP6 operates as a deubiquitinase, targeting the GOLPH3 protein in COAD and enhancing its stability. Meanwhile, circCYFIP2 is crucial for the deubiquitination of GOLPH3 protein mediated by USP6 and acts as a scaffold to confer platinum resistance. The discovery of circCYFIP2/USP6/GOLPH3 pathway offers a potential target for overcoming chemoresistance in COAD.

A Real-time augmented reality robot integrated with artificial intelligence for skin tumor surgery - experimental study and case series.

BACKGROUND: Skin tumors affect many people worldwide, and surgery is the first treatment choice. Achieving precise preoperative planning and navigation of intraoperative sampling remains a problem and is excessively reliant on the experience of surgeons, especially for Mohs surgery for malignant tumors. MATERIALS AND METHODS: To achieve precise preoperative planning and navigation of intraoperative sampling, we developed a real-time augmented reality (AR) surgical system integrated with artificial intelligence (AI) to enhance three functions: AI-assisted tumor boundary segmentation, surgical margin design, and navigation in intraoperative tissue sampling. Non-randomized controlled trials were conducted on manikin, tumor-simulated rabbits, and human volunteers in xxx Laboratory to evaluate the surgical system. RESULTS: The results showed that the accuracy of the benign and malignant tumor segmentation were 0.9556 and 0.9548, respectively, and the average AR navigation mapping error was 0.644 mm. The proposed surgical system was applied in 106 skin tumor surgeries, including intraoperative navigation of sampling in 16 Mohs surgery cases. Surgeons who have used this system highly recognize it. CONCLUSIONS: The surgical system highlighted the potential to achieve accurate treatment of skin tumors and to fill the gap in global research on skin tumor surgery systems.

HGF facilitates methylation of MEG3, potentially implicated in vemurafenib resistance in melanoma.

BACKGROUND: Melanoma, a frequently encountered cutaneous malignancy characterized by a poor prognosis, persists in presenting formidable challenges despite the advancement in molecularly targeted drugs designed to improve survival rates significantly. Unfortunately, as more therapeutic choices have developed over time, the gradual emergence of drug resistance has become a notable impediment to the effectiveness of these therapeutic interventions. The hepatocyte growth factor (HGF)/c-met signaling pathway has attracted considerable attention, associated with drug resistance stemming from multiple potential mutations within the c-met gene. The activation of the HGF/c-met pathway operates in an autocrine manner in melanoma. Notably, a key player in the regulatory orchestration of HGF/c-met activation is the long non-coding RNA MEG3. METHODS: Melanoma tissues were collected to measure MEG3 expression. In vitro validation was performed on MEG3 to prove its oncogenic roles. Bioinformatic analyses were conducted on the TCGA database to build the MEG3-related score. The immune characteristics and mutation features of the MEG3-related score were explored. RESULTS: We revealed a negative correlation between HGF and MEG3. In melanoma cells, HGF inhibited MEG3 expression by augmenting the methylation of the MEG3 promoter. Significantly, MEG3 exhibits a suppressive impact on the proliferation and migration of melanoma cells, concurrently inhibiting c-met expression. Moreover, a predictive model centered around MEG3 demonstrates notable efficacy in forecasting critical prognostic indicators, immunological profiles, and mutation statuses among melanoma patients. CONCLUSIONS: The present study highlights the potential of MEG3 as a pivotal regulator of c-met, establishing it as a promising candidate for targeted drug development in the ongoing pursuit of effective therapeutic interventions.

A Case of Primary Cutaneous CD4+ Small/Medium T-Cell Lymphoproliferative Disorder.

Primary cutaneous CD4+ small/medium T-cell lymphoproliferative disorder is indolent clinical behaviour and uncertain malignant potential. Histologically, these lesions show a predominance of small to medium-size CD4+ pleomorphic T-cell expressing follicular helper T-cell markers. We report the case of a 59-year-old female who presented with nodules on the left chest for 3 years. Dermatological examination showed four red nodules localized on the left chest with angiotelectasis without tenderness. The histopathological manifestation was consistent with the diagnosis of primary cutaneous CD4+ small/medium T-cell lymphoproliferative disorder. We focus on the clinical appearance, histopathological features, diagnosis, and differential diagnosis of primary cutaneous CD4+ small/medium T-cell lymphoproliferative disorder.

HSP90/CDC37 inactivation promotes degradation of LKB1 protein to suppress AMPK signaling in bronchial epithelial cells exposed to sulfur mustard analog, 2-chloroethyl ethyl sulfide.

To investigate the role of the liver kinase (LK) B1 protein, an activator of AMP-activated protein kinase (AMPK), in AMPK signaling suppression when exposed to vesicant, a kind of chemical warfare agent. Cultured human bronchial epithelial cells were inflicted with sulfur mustard (SM) analog, 2-chloroethyl ethyl sulfide (CEES) of 0.2-1.0 mM concentration, and cell proliferation, apoptosis, autophagy, and cellular ATP level were analyzed up to 24 h after the exposure. Focusing on LKB1, heat shock protein (HSP) 90, and cell division cycle (CDC) 37 proteins, the protein expression, phosphorylation, and interaction were examined with western blot, immunofluorescence staining, and/or immunoprecipitation. AMPK signaling was found to be inhibited 24 h after being exposed to either sub-cytotoxic (0.5 mM) or cytotoxic (1.0 mM) concentration of CEES based on MTS assay. Consistently, the degradation of the LKB1 protein and its less interaction with the HSP90/CDC37 complex was confirmed. It was found that 1.0, not 0.5 mM CEES also decreased the CDC37 protein, proteasome activity, and cellular ATP content that modulates HSP90 protein conformation. Inhibiting proteasome activity could alternatively activate autophagy. Finally, either 0.5 or 1.0 mM CEES activated HSP70 and autophagy, and the application of an HSP70 inhibitor blocked autophagy and autophagic degradation of the LKB1 protein. In conclusion, we reported here that AMPK signaling inactivation by CEES was a result of LKB1 protein loss via less protein complex formation and enhanced degradation.

Comparative Study of Highly Cross-Linked Polyethylene Liner Wear by Hip Center Location Using Elevated Hip Center Technique in Crowe I to III Hip Dysplasia: Outcomes for a Minimum of Eighteen Years of Follow-Up.

BACKGROUND: The literature has reported that supero-lateralization of the femoral head increases the rates of aseptic loosening and prosthesis revision. However, there are few reports on the influence of different hip center positions on liner wear with more than a 15-year follow-up period. METHODS: From April 2000 to August 2003, 91 patients underwent 108 total hip arthroplasties using a highly cross-linked polyethylene liner combined with zirconia femoral head and cup components. Pelvic radiographs were used to assess the vertical and horizontal distances to the center of the hip and the amount of liner wear. Mean patient age at the time of surgery was 54 years (range, 33 to 73), and mean follow-up duration was 19 years (range, 18 to 21). RESULTS: Average liner wear was 0.221 mm, with average annual wear of 0.012 mm/year. Mean vertical and horizontal distances for the hip center were 24.9 and 31.8 mm, respectively. There was no difference in linear wear between patients who had different hip center heights (<20, 20 to 30, and >30 mm), and quadrant partitioning showed no differences across the 4 quadrant zones. CONCLUSION: At a minimum of 18 years of follow-up in patients having developmental dysplasia of the hip who had different Crowe subtypes and different hip centers, elevated hip center and uncemented fixation techniques using a highly cross-linked polyethylene on ceramic components were associated with very low wear rates and excellent functional scores.

Vitamin D3 attenuates SARS-CoV-2 nucleocapsid protein-caused hyperinflammation by inactivating the NLRP3 inflammasome through the VDR-BRCC3 signaling pathway in vitro and in vivo.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection-caused coronavirus disease 2019 (COVID-19) is a global crisis with no satisfactory therapies. Vitamin D3 (VD3) is considered a potential candidate for COVID-19 treatment; however, little information is available regarding the exact effects of VD3 on SARS-CoV-2 infection and the underlying mechanism. Herein, we confirmed that VD3 reduced SARS-CoV-2 nucleocapsid (N) protein-caused hyperinflammation in human bronchial epithelial (HBE) cells. Meanwhile, VD3 inhibited the NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome activation in N protein-overexpressed HBE (HBE-N) cells. Notably, the inhibitors of caspase-1, NLRP3, and NLRP3 or caspase-1 small interference RNA (siRNA) enhanced VD3-induced NLRP3 inflammasome inactivation, with subsequent suppression of interleukin-6 (IL6) and IL1ß release in HBE-N cells, which were abolished by the NLRP3 agonist. Moreover, VD3 increased NLRP3 ubiquitination (Ub-NLRP3) expression and the binding of the VDR with NLRP3, with decreased BRCA1/BRCA2-containing complex subunit 3 (BRCC3) expression and NLRP3-BRCC3 association. VD3-induced Ub-NLRP3 expression, NLRP3 inflammasome inactivation, and hyperinflammation inhibition were improved by the BRCC3 inhibitor or BRCC3 siRNA, which were attenuated by the vitamin D receptor (VDR) antagonist or VDR siRNA in HBE-N cells. Finally, the results of the in vivo study in AAV-Lung-enhanced green fluorescent protein-N-infected lungs were consistent with the findings of the in vitro experiment. In conclusion, VD3 attenuated N protein-caused hyperinflammation by inactivating the NLRP3 inflammasome partially through the VDR-BRCC3 signaling pathway.

Collarless Polished Tapered Stems of Identical Shape Provide Differing Outcomes for Stainless Steel and Cobalt Chrome: A Biomechanical Study.

Cemented polished tapered femoral stems (PTS) made of cobalt-chrome alloy (CoCr) are a known risk factor for periprosthetic fracture (PPF). The mechanical differences between CoCr-PTS and stainless-steel (SUS) PTS were investigated. CoCr stems having the same shape and surface roughness as the SUS Exeter® stem were manufactured and dynamic loading tests were performed on three each. Stem subsidence and the compressive force at the bone-cement interface were recorded. Tantalum balls were injected into the cement, and their movement was tracked to indicate cement movement. Stem motions in the cement were greater for the CoCr stems than for the SUS stems. In addition, although we found a significant positive correlation between stem subsidence and compressive force in all stems, CoCr stems generated a compressive force over three times higher than SUS stems at the bone-cement interface with the same stem subsidence (p < 0.01). The final stem subsidence amount and final force were greater in the CoCr group (p < 0.01), and the ratio of tantalum ball vertical distance to stem subsidence was significantly smaller for CoCr than for SUS (p < 0.01). CoCr stems appear to move more easily in cement than SUS stems, which might contribute to the increased occurrence of PPF with the use of CoCr-PTS.

Photodynamic therapy combined with surgery versus Mohs micrographic surgery for the treatment of difficult-to-treat basal cell carcinoma: a retrospective clinical study.

BACKGROUND: Mohs micrographic surgery (MMS) is the preferable surgery for difficult -to-treat basal cell carcinoma (BCC) but is an expensive, labor-intensive, and time-consuming technique. The aim of this study is to compare the efficacy and safety of photodynamic therapy combined with surgery(S-PDT) versus Mohs micrographic surgery (MMS) for the treatment of difficult-to-treat BCC. METHODS: This was a retrospective, comparative study. A total of 32 patients, 16 patients with 48 lesions, were treated with S-PDT, and the other 16 patients with 17 lesions treated by MMS were enrolled in this study. Follow-up was at least 36 months posttreatment. RESULTS: The recurrence rate was no statistical difference between the S-PDT and MMS (p = 1.000, Fishers exact test). The median follow-up was 42.5 months (range 36-63 months). The mean healing time in the S-PDT [17.9 d (SD 9.8)] is longer than in MMS [7.5 d (SD 1.5)] during follow-up (p＜.001, Independent T-test). On the whole, the cosmetic outcome of patients in S-PDT was statistically no significant difference with that in MMS according to a 4-point scale (p = .719, chi-squared test). CONCLUSIONS: S-PDT is a safe, effective, and novel cosmetic treatment, which holds the potential to be an alternative treatment to MMS for some cases.

[Analysis of the curative effect of triple surgery under endoscope in the treatment of intractable heel pain].

OBJECTIVE: To investigate the clinical effect the treatment of arthroscopy-assisted calcaneal spur resection combined with plantar fascia release and calcaneal decompression in the treatment of the patients with intractable calcaneal pain. METHODS: The clinical data of 50 patients with intractable heel pain from January 2016 to January 2019 were retrospectively analyzed, including 20 males and 30 females;aged from 40 to 68 years old with an average of (50.12±7.35)years old, the medical history ranged from 1 to 4 years. All patients underwent arthroscopy-assisted calcaneal spur resection combined with plantar fascia release and calcaneal decompression, and were followed up, the duration ranged from 24 to 60 months with an average of(42.00±3.28) months. All patients had obvious heel pain before surgery, and X-ray examinations often showed the presence of calcaneal spurs. In addition to the routine foot examination, the changes in the height and angle of the arch of the foot were also measured pre and post-operatively by X-ray, for the evaluation of clinical effect. The VAS system was used to evaluate the degree of foot pain;the AOFAS scoring system was used to comprehensively evaluate the foot pain, voluntary movement, gait and stability. RESULTS: The VAS decreased from (8.75±1.24) before surgery to (5.15±2.35) at 3 months after surgery, (4.07±2.53) at 6 months after surgery, and (3.95±2.44) at the last fllow-up(P<0.05). The AOFAS score increased from (53.46±4.17) before surgery to(92.46±2.53) at 3 months after surgery, (96.33±2.46) at 6 months after surgery, and (97.05±2.37) at the last follow-up(P<0.05). The arch height was (41.54±1.15) mm before operation and (41.49±1.09) mm after the operation, the difference was not statistically significant(P>0.05). The internal arch angle of the foot arch was (121±6)° before operation and (122±7)° after operation. The difference was not statistically significant(P>0.05). CONCLUSION: Arthroscopy-assisted calcaneal bone spurs resection combined with plantar fascia release and calcaneal decompression exhibited great clinical effect for treating intractable heel.

Two-year impact of COVID-19 pandemic on hospitalized patients with skin diseases in China.

To investigate the clinical characteristics of skin disorders among hospitalized patients before and during the coronavirus disease 2019 (COVID-19) pandemic, a retrospective study was conducted based on hospitalized patients with skin diseases from Xiangya Hospital of Central South University, the largest hospital in the south-central region of China, between January 1, 2018, and December 31, 2021. A total of 3039 hospitalized patients were enrolled in the study, including 1681 patients in the prepandemic group and 1358 patients in the pandemic group. The total number of hospitalized patients in the pandemic group decreased by 19.2%, with an increased proportion of patients over 60 years of age (39.8% vs. 35.8%). Moreover, compared with the prepandemic group, there were decreases in the occurrence of most skin diseases in the pandemic group, but the proportions of keratinolytic carcinoma (6.6% vs. 5.2%), dermatitis (24.0% vs. 18.9%), and psoriasis (18.0% vs. 14.8%) were higher in the pandemic group. In addition, longer hospital stays (ß = 0.07, SE = 0.02, P = 1.35 × 10-3 ) and higher hospital costs (ß = 0.06, SE = 0.03, p = 0.031) were found in the pandemic group through general linear models, even after the corresponding adjustment. In summary, the COVID-19 pandemic has had a lasting impact on patients with skin diseases, with fewer hospitalized patients, increased proportions of older patients, longer hospital stays, and increased hospital costs. These findings will facilitate better preparation for the most effective response to future pandemics.

Prospects for Anti-Tumor Mechanism and Potential Clinical Application Based on Glutathione Peroxidase 4 Mediated Ferroptosis.

Ferroptosis, characterized by excessive iron accumulation and lipid peroxidation, is a novel form of iron-dependent cell death, which is morphologically, genetically, and biochemically distinct from other known cell death types, such as apoptosis, necrosis, and autophagy. Emerging evidence shows that glutathione peroxidase 4 (GPX4), a critical core regulator of ferroptosis, plays an essential role in protecting cells from ferroptosis by removing the product of iron-dependent lipid peroxidation. The fast-growing studies on ferroptosis in cancer have boosted a perspective on its use in cancer therapeutics. In addition, significant progress has been made in researching and developing tumor therapeutic drugs targeting GPX4 based on ferroptosis, especially in acquired drug resistance. Selenium modulates GPX4-mediated ferroptosis, and its existing form, selenocysteine (Sec), is the active center of GPX4. This review explored the structure and function of GPX4, with the overarching goal of revealing its mechanism and potential application in tumor therapy through regulating ferroptosis. A deeper understanding of the mechanism and application of GPX4-mediated ferroptosis in cancer therapy will provide new strategies for the research and development of antitumor drugs.

Angular changes in pelvic tilt and cup orientation at a minimum of eighteen years after primary total hip arthroplasty with an uncemented cup.

BACKGROUND: Changes in pelvic tilt angle (PTA) and cup orientation have been reported in patients after total hip arthroplasty, but the current literature generally has a brief follow-up period. This study will be the first to report PTA and cup orientation changes in the supine position for a minimum 18 years after total hip arthroplasty (THA) and investigate the factors associated with pelvic tilt and cup orientation changes. METHODS: In this study, 101 patients (120 hips) who underwent THA were retrospectively analyzed. The aims of our study were to evaluate the PTA and cup orientation change over 18 years after THA to assess differential PTA, cup inclination, and anteversion. We also investigated whether factors such as gender, body mass index, and age have any influence on PTA and cup orientation after THA. RESULTS: Patients showed a significant incremental change in PTA pre-operatively, immediately post-operatively, and at final follow-up. Cup orientation increased significantly at the final follow-up compared to the immediate post-operative period. Gender subgroup analysis showed that PTA was significantly greater in females than in males at the final follow-up (p = 0.025). Age subgroup analysis showed that PTA was significantly greater in the over 60 years group than in the other groups. CONCLUSION: Our patients showed significant changes in PTA and cup orientation at a minimum 18 years after surgery, especially in females over 60 years. Female patients over 60 are a risk factor after THA.

Does the Dual Mobility Cup Reduce Dislocation After Primary Total Hip Arthroplasty in Elderly Patients at High Risk of Dislocation?

OBJECTIVE: The dual mobility cup (DMC) is designed to extend the longevity of the prosthesis by improving stability, enhancing the range of motion, and decreasing impingement without increasing wear. We hypothesized that DMC would reduce the risk of dislocation in elderly patients. This study aimed to investigate the clinical and radiographic outcomes of DMC-total hip arthroplasty (THA) in elderly patients at high risk of dislocation. METHODS: From June 2016 to March 2020, 94 patients with a mean age of 77.7 years (97 hips) who underwent a posterolateral approach for DMC-THA in our department were followed up for at least one year. Preoperative and postoperative pelvic tilt angles (PTA) and DMC orientation were prospectively collected for all patients. Intraoperative and postoperative complications were recorded. A parametric test was used for normal distribution, and a non-parametric test was used for non-normal distribution. RESULTS: Abduction and anteversion angles of the cup were 42.4 and 18.0° in the supine position immediately postoperative. The average PTA for patients in the supine and standing positions were 26.5 and 34.5°, respectively. When moving from the supine to the standing position, patients experienced a mean posterior pelvic tilt of 9°. No intraoperative acetabular-related complications were recorded. Postoperative complications included early infection in one patient (1.0%) and dislocation in one patient (1.0%). CONCLUSION: Our study demonstrates that DMC-THA provides satisfactory short-term outcomes in elderly patients at a high risk of dislocation, regardless of the change in PTA resulting from postural transition.

Sulfur mustard analog 2-chloroethyl ethyl sulfide increases triglycerides by activating DGAT1-dependent biogenesis and inhibiting PGC1ɑ-dependent fat catabolism in immortalized human bronchial epithelial cells.

Using sulfur mustard analog 2-chloroethyl ethyl sulfide (CEES), we established an in vitro model by poisoning cultured immortalized human bronchial epithelial cells. Nile Red staining revealed lipids accumulated 24 h after a toxic dose of CEES (0.9 mM). Lipidomics analysis showed most of the increased lipids were triglycerides (TGs), and the increase in TGs was further confirmed using a Triglyceride-Glo™ Assay kit. Protein and mRNA levels of DGAT1, an important TG biogenesis enzyme, were increased following 0.4 mM CEES exposure. Under higher dose CEES (0.9 mM) exposure, protein and mRNA levels of PPARγ coactivator-1ɑ (PGC-1ɑ), a well-known transcription factor that regulates fatty acid oxidation, were decreased. Finally, application with DGAT1 inhibitor A 922500 or PGC1ɑ agonist ZLN005 was able to block the CEES-induced TGs increase. Overall, our dissection of CEES-induced TGs accumulation provides new insight into energy metabolism dysfunction upon vesicant exposure.HIGHLIGHTSIn CEES (0.9 mM)-injured cells:Triglycerides (TGs) were abundant in the accumulated lipids.Expression of DGAT1, not DGAT2, was increased.Expression of PGC1ɑ, not PGC1ß, was reduced.DGAT1 inhibitor or PGC1ɑ agonist blocked the CEES-mediated increase in TGs.

Current Research on Subchondral Insufficiency Fracture of the Femoral Head.

Subchondral insufficiency fracture (SIF) of the femoral head is one of the predominant etiologies of rapidly progressive osteoarthritis of the hip (RPOH). SIF is a rare disease that causes acute pain in the hip joint. It is most frequently found in elderly women with osteoporosis. It is often underdiagnosed or misdiagnosed as osteonecrosis of the femoral head. SIF is currently a well-established cause of RPOH; however, the deeper etiology of SIF is not clear. Good clinical outcomes have been reported for hip preservation therapy and hip replacement. SIF is not obvious radiologically in the early stage, and a T1-weighted magnetic resonance imaging shows a discontinuous low-intensity band under the articular cartilage convex to the articular surface as its characteristic manifestation. Some patients will lose the opportunity to preserve the hip joint due to symptoms such as progressive joint space narrowing and subchondral collapse within a very short period. Patients with progressive hip space narrowing and subchondral collapse on X-ray should be converted to total hip arthroplasty. Based on the characteristics of the disease, surgeons need to master the clinical and radiological characteristics of SIF and strive for early diagnosis and treatment.

Delay in Seeking Medical Attention and Diagnosis in Chinese Melanoma Patients: A Cross-Sectional Study.

Melanoma is a highly malignant skin tumor, and prolonged delay in seeking medical attention (DSMA) and delay in diagnosis (DD) may result in poor prognoses. Through a web-based questionnaire, we explored the related factors affecting the DSMA and DD of melanoma in a Chinese population. A total of 112 valid answer sheets were received. After obtaining the relevant information, we analyzed the factors associated with DSMA and DD. The median time of DSMA was 8.0 (quartiles: 1.0, 29.3) months, and the median of patients' DD was 1.0 (quartiles: 1.0, 8.3) month. The subsequent analysis showed that DSMA and DD were positively correlated to age and negatively correlated to education background and annual household income. Patients with a history of tumors or previous health-seeking behavior because of other skin lesions had significantly longer DSMA than those without. Patients who sought medical help at general tertiary hospitals for the first time had a significantly shorter DD than those who chose other hospitals. Our study found that DSMA and DD are associated with factors such as age, education, income, and patients' histories. Secondary prevention of Chinese melanoma should be strengthened to reduce DSMA and DD to improve patients' prognoses.

Signatures of EMT, immunosuppression, and inflammation in primary and recurrent human cutaneous squamous cell carcinoma at single-cell resolution.

Rationale: The recurrence of cutaneous squamous cell carcinoma (cSCC) after surgery is associated with the reprogramming of the tumor microenvironment (TME), and remains a key factor affecting its outcomes. Methods: We employed single-cell RNA sequencing (scRNA-seq) to examine the dynamic changes in epithelial cells, T cells, myeloid cells, and fibroblasts between primary and recurrent cSCC. Cell clustering, cell trajectory, cell-cell communication, and gene set enrichment analysis were used to investigate the TME heterogeneity between primary and recurrent cSCC. Gene expression differences were monitored by IHC staining. Results: We examined the immunosuppressed microenvironment in recurrent cSCC, which exhibited a T cell-excluded and SPP1+ tumor-associated macrophages (TAMs)-enriched status. In recurrent cSCC, CD8+ T cells showed high exhaustion and low inflammatory features, while SPP1+ TAMs displayed global pro-tumor characteristics, including decreased phagocytosis and inflammation and increased angiogenesis. Furthermore, the subgroups of SPP1+ TAMs harbored distinct functions. SPP1+ CD209high TAMs showed features of phagocytosis, while SPP1+ CD209low TAMs tended to have a high angiogenic ability. A subpopulation of tumor-specific keratinocytes (TSKs) showed significant epithelial-mesenchymal transition (EMT) features in recurrent cSCC, probably due to their active communication with IL7R + cancer-associated fibroblasts (CAFs). Moreover, we found that the pleiotropic growth factor/cytokine Midkine (MDK) could provoke different cell-cell interactions in cSCC with distinctive staging. In primary cSCC, MDK was highly expressed in fibroblasts and could promote their proliferation and block the migration of tumor cells, while in recurrent cSCC, the high expression of MDK in TSKs promoted their proliferation and metastasis. Conclusion: Our study provides insights into the critical mechanisms of cSCC progression, which might facilitate the development of a powerful approach for the prevention and treatment of cSCC recurrence.

Functional results of modified Mason-Allen suture versus horizontal mattress suture in the arthroscopic Broström-Gould procedure for chronic ankle instability.

BACKGROUND: The arthroscopic Broström-Gould procedure (ABG) gained particular attention among clinicians and researchers due to its high rate of satisfactory results. There is a lack of evidence regarding the differences in clinical outcomes for the various suture techniques. The purpose of this study was to compare the differences in clinical effect in patients treated with one-anchor modified Mason-Allen suture or two-anchor horizontal mattress suture for chronic ankle instability (CAI). METHODS: This retrospective cohort study examined CAI patients who underwent either one-anchor modified Mason-Allen suture or two-anchor horizontal mattress suture ABG between January 2018 and January 2020. Patients were divided into two groups based on the suture knot type used and the associated number of anchors. The operative time, surgical cost, Visual Analog Scale (VAS), American Orthopedic Foot & Ankle Society (AOFAS) Score, Karlsson Ankle Functional Score (KAFS), the rate of return to sports, complications, and measured biomechanical strength using standardized equipment were compared between groups. RESULTS: Sixty-four CAI patients were included (one-anchor modified Mason-Allen suture group n = 30, two-anchor horizontal mattress suture group n = 34). Compared to the two-anchor horizontal mattress suture group, the one-anchor modified Mason-Allen suture group had significantly shorter operative time (p < .001) and lower surgical cost (p < .001). There were no postoperative complications in the two groups, and no significant differences in the VAS, AOFAS, KAFS, and rate of return to sports in postoperative follow-up between the two groups at 1 and 2 years after surgery. There was no statistically significant difference in biomechanical strength anterior drawer test displacement (p > .05) between the one-anchor modified Mason-Allen suture and two-anchor horizontal mattress suture at 2 years after surgery. CONCLUSION: ABG using a one-anchor modified Mason-Allen suture showed comparable clinical results to a two-anchor horizontal mattress suture in the treatment of CAI at intermediate-term follow-up time. However, one-anchor modified Mason-Allen suture may be a faster, simpler, cost-effective substitute technology. LEVEL OF EVIDENCE: Level III, comparative study.