Two stages of salvaging an extensively necrotic foot with chronic limb-threatening ischemia by arterialization of great saphenous vein and free latissimus dorsi musculocutaneous flap transfer for wound coverage with the arterialized vein as the recipient vessel: A case report.

Patients with chronic limb-threatening ischemia (CLTI) without other options for adequate arterial revascularization could undergo deep (or distal) venous arterialization for limb salvage. Additionally, patients with extensive foot wound with CLTI sometimes require free flap transfer for limb salvage. We herein report a case of successful reconstructive limb-salvage surgery for an extensively necrotic foot with CLTI, using a two-stage operation involving venous arterialization using foot-perforating veins and subsequent free flap transfer (with preservation of the arterialized vein). The patient was a 59-year-old man with CLTI. The patient's right foot had dry necrotic tissue after Lisfranc joint amputation. Only one straight-line to the posterior tibial artery was achieved after endovascular therapies (four times). At the first stage of surgery, an arterial-venous shunt bypass from the superficial femoral artery to the distal great saphenous vein (GSV) (near the foot-perforating vein) was created. Arterial blood supply reached the necrotic area via the foot venous circulation system. At the second stage of surgery, free latissimus dorsi musculocutaneous flap (8 × 27 cm) transfer with preservation of the arterialized vein was performed. The pedicle artery was anastomosed to the bypass graft (end-to-side). The pedicle vein was anastomosed to the proximal stump of the GSV (end-to-end). The flap and residual foot survived completely, at a one-year follow-up postoperatively. An indocyanine green bypass-through angiography revealed the angiosome through the venous arterialization bypass graft, which included the flap; entire forefoot; and partial regions of the midfoot and heel. This two-stage operation might be considered a useful option for limb-salvage and complete wound-healing in patients with severe non-healing wound with CLTI. The two methods could compensate and overcome the problems of either method: incomplete wound-healing after venous arterialization, and the absence of a recipient artery for free flap transfer.

Independent Predictors of Major Adverse Cardiovascular Events at 3 Years after Aortoiliac Stent Implantation.

PURPOSE: To identify the risk factors for major adverse cardiovascular events (MACEs) in real-world practice for symptomatic peripheral artery disease in Japan. MATERIALS AND METHODS: Data on Japanese patients (N = 880) from the Observational Prospective Multicenter Registry Study on Outcomes of Peripheral Arterial Disease Patients Treated by Angioplasty Therapy for Aortoiliac Artery who underwent de novo aortoiliac stent placement. The 3-year risk of incident MACEs was investigated. RESULTS: The median age of the patients was 72.6 years (range, 34-97 years), and 83.1% of the patients were men. The patients had the following conditions: smoking (35.6%), hypertension (94.1%), dyslipidemia (81.7%), diabetes (48.0%), renal failure on dialysis (12.6%), myocardial infarction (12.7%), stroke (15.8%), and chronic limb-threatening ischemia (7.1%). Femoropopliteal lesions were present in 38.8% of the limbs with aortoiliac lesions. The 3-year rate of freedom from MACEs was 89.1%. Baseline characteristics, such as age, renal failure on dialysis, myocardial infarction, stroke, and femoropopliteal lesions, were independently associated with the risk of incident MACEs. When the study population was stratified according to these risk factors, the rate of MACEs was highest in patients with at least 3 risk factors (32.9% at 3 years). CONCLUSIONS: The 3-year rate of freedom from MACEs was reported. Baseline characteristics, such as age, renal failure on dialysis, myocardial infarction, stroke, and femoropopliteal lesions, are independent risk factors for MACEs after aortoiliac stent placement.

Limb Salvage with Multiple Modalities: A Case Report of a Diabetic Heel Ulcer Associated with Peripheral Arterial Disease.

ABSTRACT: A large diabetic heel ulcer with peripheral arterial disease is an independent predictor of limb loss; below-knee amputation is not uncommon in such cases. One treatment is multimodal therapy, which includes partial calcanectomy. Because there is a limit to the ulcer surface area that can be sutured after partial calcanectomy, the remaining raw surface is treated with another method. In this case report, the authors describe a patient with peripheral arterial disease who had a 7 × 9-cm diabetic heel ulcer. The patient was treated with partial calcanectomy after catheter-based endovascular therapy revascularization and then maggot therapy after residual-wound dimensions were reduced by negative-pressure wound therapy.

Identification of a novel gene controlling homothallism in the yeast Kazachstania naganishii isolated in Japan.

A novel gene controlling homothallic life cycle was identified in the yeast Kazachstania naganishii isolated in Japan. This gene was isolated by means of complementing a mutation, mti1, which had led to heterothallism from original homothallism in the yeast. The configuration of original mutation in MTI1 gene revealed that a truncated product is formed due to occurrence of a stop codon by a nucleotide insertion. When the gene was disrupted with a marker, the disruptant spore clone was haploid and stably heterothallic. Disfunction of the gene caused inability to self-diploidize due to defect of mating-type interconversion. The gene MTI1 (for Mating Type Interconversion) is a weak homolog of the Saccharomyces cerevisiae VID22/ENV11, which has been reported to function in vacuolar protein processing. K. naganishii has a gene representing significant homology with the HO gene of S. cerevisiae on chromosome V, which has not been clarified to be involved in regulation of life cycle in K. naganishii. The MTI1 gene defined in this study is located on K. naganishii chromosome IV and does not represent significant homology to the above ScHO-like gene and any other genes concerning life cycles of yeasts. From the viewpoint of gene evolution, it is extremely interesting that the MTI1 gene is a new type of gene controlling homothallism in addition to an HO-type gene, leading to discovery of an unknown mechanism regulating life cycles in yeasts.

Intravascular Ultrasound Imaging During Aortoiliac Stenting: No Impact on Outcomes at 1 Year.

PURPOSE: To investigate the effect of intravascular ultrasound (IVUS) imaging use on clinical outcomes after aortoiliac stenting in patients with peripheral artery disease (PAD). MATERIALS AND METHODS: Subjects for this retrospective analysis were derived from the OMOTENASHI registry database, which contained 803 symptomatic PAD patients (Rutherford categories 2-4) who were treated with self-expanding stent implantation for aortoiliac atherosclerotic lesions at 61 centers in Japan between January 2014 and April 2016. Of the 803 patients, 545 (67.9%) patients (mean age 73±9 years; 453 men) underwent IVUS-supported stent implantation and were compared with the 258 patients (mean age 73±8 years; 217 men) treated without IVUS. A propensity score analysis of 138 matched pairs was conducted to compare treatment strategies and clinical outcomes between patients having IVUS-supported endovascular therapy and those treated without IVUS. RESULTS: Endovascular strategies and postoperative medications were not significantly different between the IVUS and no-IVUS groups. A procedure time under 1 hour was less frequent in the IVUS group, which had a longer fluoroscopy time. The 12-month restenosis rate was not significantly different between the 2 groups [10.2% (95% CI 6.9 to 14.9%) vs 10.3% (95% CI 5.4 to 18.6%), p=0.99]. There was no interaction between baseline characteristics and the association of IVUS use with restenosis risk. CONCLUSION: Propensity score matching analysis revealed that duration and fluoroscopy time during IVUS-supported procedures were significantly longer than in cases without IVUS use, whereas the 12-month restenosis rate was not significantly different between the groups. IVUS use in aortoiliac lesions may be unnecessary.

The effect of physiotherapy in rotator cuff injury patients with platelet-rich plasma: study protocol of a non-randomized controlled trial.

BACKGROUND: The study aims to identify whether Platelet-rich plasma (PRP) combined with early physiotherapy has an advantage over PRP alone for rotator cuff injury patients, regarding pain release, function score, tear size, and quality of life improvement. METHODS: This is a single-center prospective non-randomized study implemented in July 2019 at the Affiliated Hospital of Southwest Medical University in Sichuan. Three hundred-forteen patients with rotator cuff injury aged over 18 years were recruited. Participants were assigned to the experiment group (PRP plus physiotherapy) or control group (PRP) by their desire. We used the Constant-Murley score to assess the shoulder function, the Visual Analogue Scale to evaluate shoulder pain, and the MOS Item Short-form Health Survey (SF-12) to measure the quality of life. MRI was applied to measure tear size, and the follow-up duration is 12 months. DISCUSSION: Our findings will give information on the effects of PRP and physiotherapy on rotator cuff injuries. Physiotherapy might be added to improve the effects of PRP in patients with rotator cuff injuries. TRIAL REGISTRATION: This study was registered in the Chinese clinical trial registry on September 1st, 2019 ( ChiCTR1900025563 ).

Independent predictors of loss of primary patency at 1 year after aortoiliac stent implantation.

To identify the risk factors for restenosis at 1 year after aortoiliac stenting for symptomatic peripheral artery disease in real-world practice. We performed subgroup analysis of a large-scale prospective multicenter registry study enrolling Japanese patients with peripheral arterial disease who underwent aortoiliac endovascular therapy from April 2014 to April 2016. The subgroup comprised 880 patients (1108 limbs) who received iliac stenting. The Rutherford class was 2, 3, and 4 in 42%, 51%, and 7% of the patients, respectively. TASC II class D disease was noted in 18% of the patients and 35% had chronic total occlusion. Mean total stent length was 82.1 ± 48.5 mm and minimum stent diameter was 9.0 ± 1.3 mm. Balloon-expandable stents were used in 8% of the limbs. Concomitant femoropopliteal lesions were present in 36% of the limbs with aortoiliac lesions. In the overall patient population, the risk of restenosis at 1 year after stenting was 11.4%. Femoropopliteal lesions and the minimum stent diameter were identified as independent risk factors for restenosis at 1 year. When the study population was stratified according to these two risk factors, the restenosis rate at 1 year was 27.1% in the patients with a minimum stent diameter < 8 mm and femoropopliteal lesions, whereas it was only 5.3% in those with a minimum stent diameter ≥ 10 mm and no femoropopliteal lesions. Femoropopliteal lesions and a smaller stent diameter were independent risk factors for restenosis at 1 year after aortoiliac stenting.

Self-Expanding Nitinol Stent vs Percutaneous Transluminal Angioplasty in the Treatment of Femoropopliteal Lesions: 3-Year Data From the SM-01 Trial.

PURPOSE: To report the midterm outcomes of a trial comparing self-expanding nitinol stents to percutaneous transluminal angioplasty (PTA) with provisional stenting in the treatment of obstructive disease in the superficial femoral and popliteal arteries. MATERIALS AND METHODS: The SM-01 study ( ClinicalTrials.gov identifier NCT01183117), a single-blinded, multicenter, randomized controlled trial in Japan, enrolled 105 consecutive patients with de novo or postangioplasty restenotic femoropopliteal lesions; after removing protocol violations (1 from each group), 51 patients (mean age 74±8 years; 36 men) in the stent group and 52 patients (mean age 73±8 years; 35 men) in the PTA group were included in the intention-to-treat analysis. The groups were well-matched at baseline. Patients were followed to 36 months with duplex imaging. Three-year primary patency was assessed based on a duplex-derived peak systolic velocity ratio <2.5. Freedom from clinically-driven target vessel revascularization (TVR) and target lesions revascularization (TLR) were estimated using the Kaplan-Meier method. RESULTS: The technical success rate was higher (100% vs 48%, p<0.001) and the frequency of vascular dissection was lower (4% vs 31%, p<0.001) in the stent group. The S.M.A.R.T stent group had a higher 3-year primary patency rate (73% vs 51%, p=0.033). Freedom from clinically-driven TVR and TLR were not significantly different between the groups. CONCLUSION: The S.M.A.R.T. stent maintained a higher primary patency rate than PTA at 3 years in this randomized trial; the need for clinically-driven revascularization was similar for both therapies.

Effects of steroidal saponins extract from Ophiopogon japonicus root ameliorates doxorubicin-induced chronic heart failure by inhibiting oxidative stress and inflammatory response.

CONTEXT: Ophiopogonis Radix, the root of Ophiopogon japonicus (Thunb.) Ker-Gawl (Liliaceae), is a Traditional Chinese Medicine, which has been investigated to possess effective treatment of cardiovascular diseases. OBJECTIVE: This study evaluates the cardioprotective effects of steroidal saponins extract from Ophiopogon japonicus (SOJ) root against doxorubicin-induced chronic heart failure (CHF) through the amelioration of oxidative stress and inflammation. MATERIALS AND METHODS: A Sprague-Dawley rat model of CHF was established by intraperitoneally injected with DOX. All rats were randomly divided into four groups: Control group, CHF group, CHF + SOJ (100 mg/kg) treatment group, SOJ (100 mg/kg) treatment group (n = 8/group). After six weeks administration, biometric and echocardiography were measured. The levels of biochemical parameters were measured using commercial kits. RESULTS: The values of LVESP, +dP/dtmax, -dP/dtmax, EF and FS increased to 116.20 ± 1.68 mmHg, 2978.71 ± 168.26 mmHg/s, 3452.61 ± 286.09 mmHg/s, 68.26 ± 5.28% and 31.97 ± 3.79%, respectively; the values of LVEDP, LVESD and LVEDD decreased to 8.85 ± 0.84 mmHg, 8.39 ± 0.45 mm and 12.36 ± 0.87 mm in CHF + SOJ group. In addition, the levels of IL-6, TNF-α and IL-1ß decreased to 154.41 ± 7.72 pg/mg protein, 110.02 ± 6.96 pg/mg protein and 39.39 ± 5.27 pg/mg protein, respectively; the relative activity of p38 MAPK decreased to 2.60 ± 0.40 in CHF + SOJ group. Furthermore, the activities of SOD, CAT and GSH-Px increased to 268.77 ± 6.20 U/mg protein, 13.68 ± 0.68 U/mg protein and 316.90 ± 8.08 µmol/mg protein, and the content of MDA decreased to 4.03 ± 0.43 nmol/mg protein in CHF + SOJ group. CONCLUSIONS: SOJ exerts the cardioprotective effect against DOX-induced CHF through suppressing inflammatory and oxidative stress. These results provide evidence that SOJ might be an effective treatment for CHF.

Clinical features and predictors of patients with critical limb ischemia who responded to autologous mononuclear cell transplantation for therapeutic angiogenesis.

The clinical features of patients with critical limb ischemia (CLI) who responded to angiogenesis using autologous peripheral blood mononuclear cell transplantation (PB-MNC) have not yet been fully characterized, and there are no useful predictors to judge the curative effect in the early period after PB-MNC. This study sought to clarify the clinical features and predictors in patients with CLI who were successfully treated using PB-MNC. 30 consecutive patients [arteriosclerosis obliterans: 24 patients, thromboangiitis obliterans: 6 patients] who were diagnosed with major amputation despite maximal medical therapy were enrolled in this study. The study endpoint was major amputation within 3 months after PB-MNC. The collected data were evaluated for correlation between patients with and without major amputation within 3 months after PB-MNC. Six patients underwent major amputation and 1 patient underwent minor amputation. In the patients with major amputation, transcutaneous oxygen tension before PB-MNC and transplanted CD34-positive cells were lower than those of patients without major amputation. In the patients with amputation, interleukin-6 (IL-6) continued to increase after the first PB-MNC, and basic fibroblast growth factor (bFGF) decreased within 3 days after the first PB-MNC. PB-MNC was useful for the patients who were managed for inflammation and who had revascularization of the upper-popliteal arteries and two of the infra-popliteal arteries by endovascular and/or surgical revascularization. Variation in IL-6 and bFGF in the early period after PB-MNC could be useful predictors for the requirement of amputation within 3 months after PB-MNC.

Penetration rate of the placement of a drug-eluting stent for the treatment of superficial femoral artery lesions in Japan.

Stent placement for treating superficial femoral artery (SFA) lesions has been approved. The Zilver PTX stent, a drug-eluting stent (DES) for treating SFA lesions, has been available in Japan since 2012. However, the penetration rate of this DES has not yet been reported. This prospective multicenter registry study enrolled 314 patients (354 limbs) to be treated by stent placement in 2014 (UMIN000011551). The primary endpoint was the measurement of the penetration rate of the DES. The secondary endpoints were measuring the freedom from restenosis, freedom from target lesion revascularization (TLR), freedom from major adverse limb event (MALE), and the survival rate at 12 months postoperatively. Female patients comprised 28% participants. The mean age was 73.1 ± 9.2 years. A total of 56% patients had diabetes mellitus (DM), 36% patients were receiving hemodialysis, and 30% used cilostazol at baseline. The mean lesion length was 156 ± 101 mm, and the percentage of TASC II C/D lesions was 58%. Critical limb ischemia (CLI) was observed in 32% limbs. The penetration rates of the Zilver PTX stent were only 8%. The primary patency rate was similar between DES and bare-metal stents (BMS) at 12 months postoperatively (77 vs. 84%, p = 0.52). In this study, the rates of freedom from restenosis, freedom from TLR, freedom from MALE, and the survival rate at 12 months postoperatively were 83, 86, 85, and 89%, respectively. The penetration rate of a first-generation DES placement for treating SFA lesions is low in Japan. On the other hand, BMS is well utilized and its primary patency is acceptable.

Effect of Whole-Body-Vibration Training on Trunk-Muscle Strength and Physical Performance in Healthy Adults: Preliminary Results of a Randomized Controlled Trial.

CONTEXT: Whole-body-vibration (WBV) stimulus equipment has been used as a new training method for health promotion. Its use in the clinic has expanded to the field of sports and rehabilitation for disabled patients. WBV training is rapidly gaining popularity in health and fitness centers as an alternative method for improving muscle performance. Acute positive effects of WBV have been shown on lower-extremity muscle power and vertical-jump ability; however, there have not been any studies focusing on the long-term effects of WBV for trunk muscle and dynamic balance. OBJECTIVE: To investigate the effects of an 8-wk program of WBV in combination with trunk-muscle training on muscle performance in healthy, untrained adults. DESIGN: Laboratory-based, repeated-measures study. SETTING: University laboratory. PARTICIPANTS: 20 healthy university men. INTERVENTION: Participants were randomly assigned to a WBV or non-WBV group. The WBV group performed a trunk-muscle-training program in combination with WBV; the non-WBV group performed the same muscle-training program without WBV for 8 wk. MAIN OUTCOME MEASURES: In the pre- and posttraining period, the participants were evaluated using the Functional Movement Screen (FMS), Y Balance Test (Y-test) (anterior, posteromedial, and posterolateral reach), trunk-muscle isometric strength (flexor, extensor, and flexor:extensor ratio), squat jump, and countermovement jump. RESULTS: The WBV group had greater improvement than the non-WBV group in both trunk-flexor muscle strength (P = .02) and the Y-test (anterior reach) (P = .004) between pre- and posttraining. CONCLUSION: Adding WBV to a trunk-muscle-strengthening program may improve trunk-flexor isometric strength and anterior reach during the Y-test more than training without WBV. The WBV protocol used in this study had no significant impact on FMS scores, squat jumping, countermovement jumping, trunk-extensor isometric strength, or trunk flexor:extensor ratio.

Relationships between problematic behaviors and motor abilities of children with cerebral palsy.

[Purpose] This study aimed to examine whether motor abilities of children with cerebral palsy are related to their problematic behaviors. [Subjects] The subjects were children with mental retardation who were undergoing physical therapy. [Methods] Twenty-one examiners, 13 physical therapists, and 8 occupational therapists treated and examined the subjects by using the Japanese version of the Aberrant Behavior Checklist. The Japanese version of the Aberrant Behavior Checklist scores were compared between the Gross Motor Function Classification System I to III (12 subjects) and Gross Motor Function Classification System IV and V groups (17 subjects). [Results] Lethargy and stereotypy scores significantly differed between the groups, proving that patients with Gross Motor Function Classification System levels IV and V have more severe problematic behaviors. [Conclusion] In this study, only five types of problematic behaviors, namely irritability, lethargy, stereotypy, hyperactivity, and inappropriate speech, were examined. Despite this limitation, the study clarifies that problematic behaviors of children with cerebral palsy, except lethargy and stereotypy, have little relationship with their motor abilities.

Cilostazol reduces angiographic restenosis after endovascular therapy for femoropopliteal lesions in the Sufficient Treatment of Peripheral Intervention by Cilostazol study.

BACKGROUND: It remains unclear whether cilostazol, which has been shown to improve the clinical outcomes of endovascular therapy for femoropopliteal lesions, also reduces angiographic restenosis. METHODS AND RESULTS: The Sufficient Treatment of Peripheral Intervention by Cilostazol (STOP-IC) study investigated whether cilostazol reduces the 12-month angiographic restenosis rate after percutaneous transluminal angioplasty with provisional nitinol stenting for femoropopliteal lesions. Two hundred patients with femoropopliteal lesions treated from March 2009 to April 2011 at 13 cardiovascular centers were randomly assigned 1:1 to receive oral aspirin with or without cilostazol. The primary end point was 12-month angiographic restenosis rate. Secondary end points were the restenosis rate on duplex ultrasound, the rate of major adverse cardiac events, and target lesion event-free survival. Researchers evaluated all follow-up data and assessed the end points in a blinded fashion. The mean lesion length and reference vessel diameter at the treated segment were 128±86 mm and 5.4±1.4 mm, respectively. The frequency of stent used was similar between groups (88% versus 90% in the cilostazol and noncilostazol group, respectively, P=0.82). During the 12-month follow-up period, 11 patients died and 152 patients (80%) had evaluable angiographic data at 12 months. The angiographic restenosis rate at 12 months was 20% (15/75) in the cilostazol group versus 49% (38/77) in the noncilostazol group (P=0.0001) by intention-to-treat analysis. The cilostazol group also had a significantly higher event-free survival at 12 months (83% versus 71%, P=0.02), although cardiovascular event rates were similar in both groups. CONCLUSIONS: Cilostazol reduced angiographic restenosis after percutaneous transluminal angioplasty with provisional nitinol stenting for femoropopliteal lesions. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00912756; and URL: https://www.umin.ac.jp. Unique identifier: UMIN000002091.

[Heparin-induced thrombocytopenia developed during the acute phase after left upper lobectomy for lung cancer].

Heparin-induced thrombocytopenia (HIT) is a serious adverse effect of heparin administration. This must not be rarely encountered but is not often reported in Japan compared to Western countries. A 68-year-old woman underwent left upper lobectomy for lung cancer. Low-dose unfractionated heparin was administrated to prevent thromboembolism after the operation. Two days later, sudden dyspnea appeared and ultracardiosonography showing an extensive thromboembolus from the main trunk to both main branches of pulmonary artery indicated pulmonary embolization. After the establishment of percutaneous cardiopulmonary support (PCPS) support, the embolus was removed by emergent open heart surgery. However, despite further unfractionated heparin administration following embolization surgery, other thrombus was identified in both the bi-lateral internal jagular veins and inferior vena cava by ultrasonography and contrast computed tomography( CT). Her platelet count was decreased gradually despite platelet transfusion. Plate factor 4( PF4) antibody against heparin in her blood examination was found, and HIT II was diagnosed. Discontinuation of unfractionated heparin and administration of antithrombin agent improved platelet count, and no additional embolization was identified.

[Resected thymic hyperplasia with myasthenia gravis and Lambert-Eaton myasthenic syndrome].

A 61-year-old male who noticed muscular weakness of his extremities, diplopia and slur his words was found to have a thymic tumor on computed tomography. The immunological examination showed incremental of anti Acetylcholine receptor antibody titer and anti P/Q-type voltage-gated calcium channels antibody titer. Electromyography showed decremental response to low frequency stimulations, and incremental response to high frequency stimulations. So he was diagnosed with thymic tumor combined with myasthenia gravis and Lambert-Eaton myasthenic syndrome. He treated with extended thymomectomy resulting in the improvement of his neurological symptoms. Five years after operation, the patient is well without any malignant diseases.

A pan-cancer analysis of the oncogenic and immunological roles of transglutaminase 1 (TGM1) in human cancer.

BACKGROUND: There is currently a limited number of studies on transglutaminase type 1 (TGM1) in tumors. The objective of this study is to perform a comprehensive analysis across various types of cancer to determine the prognostic significance of TGM1 in tumors and investigate its role in the immune environment. METHOD: Pan-cancer and mutational data were retrieved from the TCGA database and analyzed using R (version 3.6.4) and its associated software package. The expression difference and prognosis of TGM1 were examined, along with its correlation with tumor heterogeneity, stemness, mutation landscape, and RNA modification. Additionally, the relationship between TGM1 expression and tumor immunity was investigated using the TIMER method. RESULTS: TGM1 is expressed differently in various tumors and normal samples and is associated with the overall survival and progression-free time of KIRC, ACC, SKCM, LIHC, and STES. In LICH, we found a negative correlation between TGM1 expression and 6 indicators of tumor stemness. The mutation frequencies of BLCA, LIHC, and KIRC were 1.7%, 0.3%, and 0.3% respectively. In BLCA and BRCA, there was a significant correlation between TGM1 expression and the infiltration of CD4 + T cells, CD8 + T cells, neutrophils, and dendritic cells. CONCLUSION: TGM1 has the potential to serve as both a prognostic marker and a drug target.

Network Analysis of Osteoarthritis Progression Using a Steiner Minimal Tree Algorithm.

Purpose: To provide a comprehensive analysis of associated genes with osteoarthritis (OA). Here, we reported a network analysis of OA progression by using a Steiner minimal tree algorithm. Methods: We collected the OA-related genes through screening the publications in MEDLINE. We performed functional analysis to analyze the associated biochemical pathways of the OA-related genes. Pathway crosstalk analysis was constructed to explore interactions of the enriched pathways. Steiner minimal tree algorithm was used to analyze molecular pathway networks. The average clustering coefficient was compared with the corresponding values of the Osteoarthritis-specific network. The new finding RNA was compared with former single-cell RNA-seq analysis results. Results: A gene set with 177 members reported to be significantly associated with Osteoarthritis was collected from 187 studies. Functional enrichment analysis revealed a specific related-OA gene including skeletal system development, cytokine-mediated signaling pathway, inflammatory response, cartilage development, and extracellular matrix organization. We performed a pathway crosstalk analysis among the 72 significantly enriched pathways. A total of 151 of the 177 genes in the Osteoarthritis gene set were included in the human interactome network. There were 31 genes in the former single-cell RNA-seq analysis results. The CLU, ENO1, SRRM1, UBC, HMGB1, NR3C1, NOTCH2NL, and CBX5 have significantly increased expression in seven molecularly defined populations of OA cartilage. Conclusion: The Steiner tree-based approach finds new biological molecules associated with OA genes.

Natural products and derivatives in renal, urothelial and testicular cancers: Targeting signaling pathways and therapeutic potential.

BACKGROUND: Natural products have demonstrated significant potential in cancer drug discovery, particularly in renal cancer (RCa), urothelial carcinoma (UC), and testicular cancer (TC). PURPOSE: This review aims to examine the effects of natural products on RCa, UC and TC. STUDY DESIGN: systematic review METHODS: PubMed and Web of Science databases were retrieved to search studies about the effects of natural products and derivatives on these cancers. Relevant publications in the reference list of enrolled studies were also checked. RESULTS: This review highlighted their diverse impacts on key aspects such as cell growth, apoptosis, metastasis, therapy response, and the immune microenvironment. Natural products not only hold promise for novel drug development but also enhance the efficacy of existing chemotherapy and immunotherapy. Importantly, we exert their effects through modulation of critical pathways and target genes, including the PI3K/AKT pathway, NF-κB pathway, STAT pathway and MAPK pathway, among others in RCa, UC, and TC. CONCLUSION: These mechanistic insights provide valuable guidance for researchers, facilitating the selection of promising natural products for cancer management and offering potential avenues for further gene regulation studies in the context of cancer treatment.

Pan-cancer analysis of RNA 5-methylcytosine reader (ALYREF).

The increasing interest in RNA modifications has significantly advanced epigenomic and epitranscriptomic technologies. This study focuses on the immuno-oncological impact of ALYREF in human cancer through a pan-cancer analysis, enhancing understanding of this gene's role in cancer. We observed differential ALYREF expression between tumor and normal samples, correlating strongly with prognosis in various cancers, particularly kidney renal papillary cell carcinoma (KIRP) and liver hepatocellular carcinoma (LIHC). ALYREF showed a negative correlation with most tumor-infiltrating cells in lung squamous cell carcinoma (LUSC) and lymphoid neoplasm diffuse large B-cell lymphoma (DLBC), while positive correlations were noted in LIHC, kidney chromophobe (KICH), mesothelioma (MESO), KIRP, pheochromocytoma and paraganglioma (PARD), and glioma (GBMLGG). Additionally, ALYREF expression was closely associated with tumor heterogeneity, stemness indices, and a high mutation rate in TP53 across these cancers. In conclusion, ALYREF may serve as an oncogenic biomarker in numerous cancers, meriting further research attention.