Microbiological Distribution, Antimicrobial Susceptibility and Risk Factors of Polymicrobial Infections in Diabetic Foot.

BACKGROUND: Diabetic foot infection (DFI) leads to poor prognosis and polymicrobial infections are usually the main cause. The study is to explore the microbiological distribution, antimicrobial drug susceptibility, and risk factors of polymicrobial infections in hospitalized patients with DFI. METHODS: This retrospective study included 160 patients with DFI in Wagner's grades 2, 3, and 4. Deep necrotic tissue was used to acquire specimens for microbiological culture. VITEK-2 system and MALDI-TOF mass spectrometry were used to identify the bacterial isolates. The Kirby Bauer method was used for drug susceptibility tests. RESULTS: A total of 202 pathogens were isolated. The proportion of gram-negative bacilli (GNB, 62.4%, 126 of 202) was higher than that of gram-positive cocci (GPC, 37.6%, 76 of 202). The most prevalent GPC was Staphylococcus aureus in every Wagner grade, while the most common GNB varied in different Wagner grades. Linezolid was the most effective antibiotic for GPC in different Wagner grades. Imipenem was the most effective antibiotic for GNB in Wagner grade 2. Amikacin was the most effective antibiotic for GNB in Wagner grades 3 and 4. Polymicrobial infections existed only in Wagner grades 3 and 4 and increased the risk of amputation (p < 0.01). History of antibiotics, duration of diabetic foot, CRP, and lower extremity arterial disease were the independent risk factors of polymicrobial infections (p < 0.05). CONCLUSIONS: Clinicians should adjust the antibiotic as needed based on the results of drug susceptibility and clinical treatment effect among different Wagner grades. Particular attention should be given to the treatment of polymicrobial infections.

Chloroform associated with bone mineral density and bone mineral content in adults: A population-based cross-sectional research.

BACKGROUND: Bone mineral density is an important indicator of osteoporosis, and its variation with volatile organic compounds exposure has rarely been studied. However, the relationship between chloroform (an essential volatile organic compounds component) and bone mineral density remains unclear. Consequently, we aimed to explore the relationship between chloroform alone and bone mineral density or bone mineral content. METHODS: Herein, 2,553 individuals aged 18 and above from the National Health and Nutrition Examination Surveys (NHANES) in 2009-2010, 2013-2014, and 2017-2020, were included. We employed two independent t-tests and multi-linear regression models to statistically assess the relationship between chloroform exposure and BMD/BMC in the spine and femoral area. RESULTS: A "V"-shaped correlation between chloroform exposure and bone mineral density or bone mineral content (BMD/BMC) was observed in the unadjusted model, particularly in the Ward's triangle and femoral neck as a whole. A negative correlation was specifically observed for the Ward's triangle BMD/BMC and L4 BMD/BMC. On the other hand, in the adjusted model, a dominantly negative correlation between the L4 BMC and chloroform exposure was observed over a range of exposure levels. The subgroup analysis revealed a negative correlation between chloroform concentrations and BMC in the femur and spine, especially in women and the 65-80 age population. CONCLUSION: Our study revealed a "V" shaped correlation between chloroform and BMD/BMC of the femur and spine in U.S. adults. This finding highlights the fact that prolonged exposure to chloroform may cause the changes in BMD/BMC.

Neoadjuvant chemo-immunotherapy with camrelizumab plus nab-paclitaxel and cisplatin in resectable locally advanced squamous cell carcinoma of the head and neck: a pilot phase II trial.

Neoadjuvant chemoimmunotherapy has emerged as a potential treatment option for resectable head and neck squamous cell carcinoma (HNSCC). In this single-arm phase II trial (NCT04826679), patients with resectable locally advanced HNSCC (T2‒T4, N0‒N3b, M0) received neoadjuvant chemoimmunotherapy with camrelizumab (200 mg), nab-paclitaxel (260 mg/m2), and cisplatin (60 mg/m2) intravenously on day one of each three-week cycle for three cycles. The primary endpoint was the objective response rate (ORR). Secondary endpoints included pathologic complete response (pCR), major pathologic response (MPR), two-year progression-free survival rate, two-year overall survival rate, and toxicities. Here, we report the perioperative outcomes; survival outcomes were not mature at the time of data analysis. Between April 19, 2021 and March 17, 2022, 48 patients were enrolled and received neoadjuvant therapy, 27 of whom proceeded to surgical resection and remaining 21 received non-surgical therapy. The ORR was 89.6% (95% CI: 80.9, 98.2) among 48 patients who completed neoadjuvant therapy. Of the 27 patients who underwent surgery, 17 (63.0%, 95% CI: 44.7, 81.2) achieved a MPR or pCR, with a pCR rate of 55.6% (95% CI: 36.8, 74.3). Treatment-related adverse events of grade 3 or 4 occurred in two patients. This study meets the primary endpoint showing potential efficacy of neoadjuvant camrelizumab plus nab-paclitaxel and cisplatin, with an acceptable safety profile, in patients with resectable locally advanced HNSCC.

Gasless robot-assisted transaxillary hemithyroidectomy (RATH): learning curve and complications.

PURPOSE: Gasless robot-assisted transaxillary hemithyroidectomy (RATH) is regarded as an alternative surgical option for thyroid operations. However, the associated steep learning curve is a clinical concern. This study evaluated the learning curve of RATH for surgeons without experience of endoscopic surgery and the early surgical outcomes of RATH. METHODS: We conducted a retrospective study of patients who underwent gasless RATH and conventional hemithyroidectomy (CH) at Sun Yat-sen University Cancer Center, Guangzhou, China, from June 2021 to August 2022. The learning curve and early surgical outcomes of gasless RATH were evaluated. And the early surgical outcomes of gasless RATH were compared to CH. RESULTS: In total, 105 patients who underwent gasless RATH and 104 patients who underwent CH were matched and assessed. The cumulative sum techniques (CUSUM) analysis showed that the peak point of gasless RATH operative time occurred at the 31st case. No clear single peak was identified in the CUSUM plot for drainage amount and blood loss. No significant difference in perioperative complications was observed between these two groups. Moreover, the number of postoperative patients who got sense of thyroid area traction were fewer in the gasless RATH group (n = 11, 10.5%) than in the CH group (n = 32, 30.8%). CONCLUSION: Gasless RATH can be considered as an alternative approach to the conventional open procedure, as it is an easy remote access technique, with shorter learning curves and certain advantage such as less sense of thyroid area traction.

Evaluation of a new low-cost negative pressure wound therapy in the treatment of diabetic foot ulcers.

OBJECTIVE: To investigate the effectiveness of a new and low-cost negative pressure wound therapy (LC-NPWT) in the treatment of diabetic foot ulcers (DFUs). METHOD: In this retrospective cohort study, patients from our inpatient clinic with Wagner grade 3 DFUs were given LC-NPWT or conventional wound dressings. The primary outcome was the wound healing rates. Complete wound healing, defined as complete re-epithelialisation of the wound, was recorded during the two months of follow-up. The definition of complete epidermis of the wound was that the skin was closed (100% re-epithelialisation), with no drainage or dressing. The secondary outcomes were the number of inpatient days and surgical procedures, and outcomes after hospital discharge. The wound score from the Bates-Jensen wound assessment tool and the levels of the inflammation factors procalcitonin (PCT), C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) were compared between the two groups. The Kaplan-Meier survival estimate was used to examine the cumulative wound healing rate. RESULTS: The study cohort comprised 41 patients. The two-month wound healing rate was higher in patients in the LC-NPWT group than in the control group (15/21 (71.4%) versus 8/20 (40.0%), respectively; p=0.043). At the end of the two-month follow-up period, the cumulative wound healing rate was higher in the LC-NPWT group than in the control group (p=0.032). Patients in the LC-NPWT group had fewer inpatient days (19.3±3.84 versus 25.05±4.81; p<0.001) and shorter duration of antibiotic use (32.14±3.89 days versus 36.10±5.80 days; p=0.014) than those who received conventional wound dressings. There were significant improvements in mean wound score between the LC-NPWT group and the control group (p<0.001). After one week of treatment, the blood levels of PCT (0.03±0.30ng/ml versus 0.07±0.08ng/ml; p=0.039), CRP (14.55±13.40mg/l versus 24.71±18.10mg/l; p=0.047) and ESR (42.05±29.29mm/h versus 61.65±22.42mm/h; p=0.021) were lower in patients who received LC-NPWT than those who received conventional wound dressings. CONCLUSION: LC-NPWT is effective in the treatment of DFUs and provides a cheaper alternative for patients with DFUs that could potentially alleviate the economic distress these patients endure.

Retrospective assessment of neoadjuvant camrelizumab combined with induction chemotherapy: efficacy in laryngeal preservation for advanced hypopharyngeal and laryngeal squamous cell carcinoma.

BACKGROUND: Hypopharyngeal and laryngeal squamous cell carcinoma (SCC) account for 25-30% of head and neck SCC. Total laryngectomy, while effective, compromises the quality of life. Immune checkpoint inhibitors such as Camrelizumab offer potential in laryngeal preservation. The study investigated Camrelizumab combined with TP regimen as a neoadjuvant therapy for laryngeal preservation in advanced hypopharyngeal and laryngeal SCC. METHODS: A retrospective study was conducted at Sun Yat-sen University Cancer Center on patients diagnosed with locally advanced SCC of the hypopharynx and larynx from October 1, 2019, to October 25, 2022. The efficacy of a first-line treatment combining Camrelizumab (200 mg) and TP regimen (Albumin-bound paclitaxel at 260 mg/m2 and Cisplatin at 60 mg/m2) was evaluated using RECIST 1.1 criteria. Outcomes included overall survival (OS), progression-free survival (PFS), laryngectomy-free survival (LFS), and response rates. RESULTS: Of the 71 included patients, the median age was 60.7 years. Post the first-line treatment, 90.1% demonstrated an overall response. The one-year and two-year OS rates were 91.5% and 84.3%, respectively. One-year and two-year PFS rates were 92.9% and 83.9%, respectively, with LFS at 85.6% and 73.2%. The initial T4 stage as significantly associated with reduced OS and LFS. Skin reaction was the predominant adverse event. CONCLUSION: The Camrelizumab-TP regimen demonstrated promising results for advanced hypopharyngeal/laryngeal SCC patients, exhibiting high response rates, OS, and LFS, positioning it as a potential primary option for laryngeal preservation. Further comprehensive, randomized controlled studies are imperative to validate these initial observations and elucidate the regimen's full clinical efficacy in optimizing laryngeal outcomes.

Association between serum heavy metal levels and diabetic retinopathy in NHANES 2011-2020.

The present study utilized the National Health and Nutrition Examination Survey (NHANES) database to examine the relationship between serum levels of heavy metals and Diabetic retinopathy (DR) in individuals aged over 30 years with type 2 diabetes mellitus (T2DM) in the United States. A cross-sectional analysis was conducted on 1583 individuals with T2DM from the NHANES 2011-2020, including 331 individuals in the DR group and 1252 individuals in the non-DR group. We collected data on serum levels of heavy metals, DR, and serum albumin for descriptive statistics, linear regression, and logistical regression analysis. After adjusting for age, gender, race and other factors, there was no statistically significant association between blood cadmium, selenium, mercury, or lead and DR. However, serum manganese (Mn) and DR had a significant negative association (ß = - 0.2045, 95% CI = - 0.3484, - 0.0606). Serum albumin partially modulated the indirect influence of serum Mn on the incidence of DR, accounting for 12.80% of the association between serum Mn and DR. There was a negative association between serum Mn levels and the prevalence of DR in people with T2DM. Mn intake at least in this study has a little influence on the onset and development of DR.

Mouse islet-derived stellate cells are similar to, but distinct from, mesenchymal stromal cells and influence the beta cell function.

AIMS: Evidence is accumulating of the therapeutic benefits of mesenchymal stromal cells (MSCs) in diabetes-related conditions. We have identified a novel population of stromal cells within islets of Langerhans - islet stellate cells (ISCs) - which have a similar morphology to MSCs. In this study we characterize mouse ISCs and compare their morphology and function to MSCs to determine whether ISCs may also have therapeutic potential in diabetes. METHODS: ISCs isolated from mouse islets were compared to mouse bone marrow MSCs by analysis of cell morphology; expression of cell-surface markers and extracellular matrix (ECM) components; proliferation; apoptosis; paracrine activity; and differentiation into adipocytes, chondrocytes and osteocytes. We also assessed the effects of co-culture with ISCs or MSCs on the insulin secretory capacity of islet beta cells. RESULTS: Although morphological similar, ISCs were functionally distinct from MSCs. Thus, ISCs were less proliferative and more apoptotic; they had different expression levels of important paracrine factors; and they were less efficient at differentiation down multiple lineages. Co-culture of mouse islets with ISCs enhanced glucose induced insulin secretion more effectively than co-culture with MSCs. CONCLUSIONS: ISCs are a specific sub-type of islet-derived stromal cells that possess biological behaviors distinct from MSCs. The enhanced beneficial effects of ISCs on islet beta cell function suggests that they may offer a therapeutic target for enhancing beta cell functional survival in diabetes.

Neoadjuvant chemoimmunotherapy shows major pathological response and low recurrence in head and neck squamous cell carcinoma.

BACKGROUND: The study aimed to investigate the efficacy and survival outcomes of neoadjuvant chemotherapy combined with programmed cell death protein 1 (PD-1) blockade (neoadjuvant chemoimmunotherapy) for patients with resectable head and neck squamous cell carcinoma (HNSCC). METHODS: A retrospective analysis was conducted. Patients with initially diagnosed, resectable HNSCCs who received the neoadjuvant chemoimmunotherapy and radical surgery were included. Correlation analysis between patients' clinical characteristics and pathological responses, and survival analysis were performed. RESULTS: A total of 79 patients were included. The majority of patients (55, 69.6%) were diagnosed at locally advanced stages and most of them (58, 73.4%) had tumor located at the oral cavity. Nearly half of patients (35, 44.3%) received two cycles of neoadjuvant chemoimmunotherapy and the rest had three or more cycles. The R0 resection rate was 98.7%. In the pathological evaluation, 53.1% of patients reached pathological complete responses or major pathological responses. After a median follow-up of 17.0 months, the 1-year disease-free survival (DFS) and overall survival (OS) rates were 87.2% and 97.4%, respectively. The pathological response showed a significantly positive association with survival benefits (p < 0.001). Patients with human papillomavirus (HPV)-positive oropharyngeal cancer had the best pathological response and survival outcomes. Besides, history of radiation at head and neck region and poor pathological response were found to be independent risk factors of DFS for patients receiving such treatments. CONCLUSION: Neoadjuvant chemoimmunotherapy of HNSCC showed high rate of pathological response and low recurrence rate, holding promise for becoming the new standard of care for resectable HNSCC.

Relationship between body fat ratio and inflammatory markers in a Chinese population of adult male smokers.

Objective: To explore the correlation between changes in the body fat ratio (BFR) and peripheral blood inflammatory markers according to smoking status in the adult Chinese male population. Methods: A total of 865 participants (aged 20-70 years) were included. All participants underwent a physical health examination at Xiguzhou Central Hospital between October 2015 and July 2016, including measurements of body mass index (BMI), BFR, white blood cell [WBC] count, and neutrophil-lymphocyte ratio [NLR]. Results: WBCs count and NLR were significantly higher in adult male smokers than in non-smokers (P = 0.00). According to the BFR stratification analysis, WBC count and NLR significantly increased in accordance with BFR (P = 0.00). This finding remained significant after adjusting for relevant confounding factors (P < 0.05). Two-factor stratified analysis of smoking status and BFR showed that WBC count and NLR in the smoking population were higher than in nonsmokers, regardless of BFR. The interaction model showed that BFR and smoking status affected WBC count and NLR changes (P < 0.05). A significant positive correlation was found between WBC count, NLR, and BFR in adult male smokers; however, there was no significant correlation with BMI. There was an interaction between smoking and BFR, both of which synergistically affected changes in inflammatory markers, including WBC count and NLR. Conclusion: WBC count and NLR of smokers with a high BFR were significantly higher than those of nonsmokers with a low BFR. It is important to provide evidence-based medical evidence for social tobacco control and to reduce BFR.

PD-1 Inhibitors combined with paclitaxel (Albumin-bound) and cisplatin for larynx preservation in locally advanced laryngeal and hypopharyngeal squamous cell carcinoma: a retrospective study.

BACKGROUND: laryngeal and hypopharyngeal squamous cell carcinoma (SCC) is a common head and neck cancer with significant impact on quality of life due to its crucial roles in vocalization, airway protection, and swallowing. This retrospective study aims to evaluate the efficacy and larynx organ preservation of neoadjuvant treatment with PD-1 inhibitors in combination with paclitaxel (Albumin-bound) and cisplatin for locally advanced laryngeal and hypopharyngeal SCC. METHODS: Medical records of consecutive patients diagnosed with histologically or cytologically confirmed locally advanced SCC of the larynx and hypopharynx, who received PD-1 inhibitor therapy at a single tertiary care center, were reviewed from January 1, 2019, to December 15, 2022. The patients were treated with a combination of PD-1 inhibitors, paclitaxel (Albumin-bound) 260mg/m2, and cisplatin 60mg/m2 (TP) as their first-line therapy. Survival outcomes, laryngectomy-free survival (LFS) rates and response rates were assessed. RESULTS: The study cohort comprised 156 patients, predominantly male, with a median age of 60.4 years. The estimated one-year overall survival (OS) rate was 94.1%, two-year OS rate was 82.5%, one-year progression-free survival (PFS) rate was 80.4%, and two-year PFS rate was 66.3%. The one-year LFS was 86.4%, and the two-year LFS rate was 73.0%. The overall response rate after TP + PD-1 inhibitors therapy was 88.5%. Common treatment-associated adverse events included rash, thyroid function abnormalities, myelosuppression, and colitis. CONCLUSION: Neoadjuvant therapy with PD-1 inhibitors in combination with paclitaxel (Albumin-bound) and cisplatin showed promising efficacy and tolerability for larynx preservation in locally advanced laryngeal and hypopharyngeal SCC. The high response rates and favorable survival outcomes suggest this approach as a potential treatment option. Prospective randomized controlled trials are needed to further validate these findings and establish the role of immunotherapy in larynx preservation.

Evaluation of neoadjuvant chemotherapy combined with PD-1 inhibitors in patients with oropharyngeal and hypopharyngeal squamous cell carcinoma: a comparative study of antitumor activity.

PURPOSE: To assess the antitumor activity of neoadjuvant chemotherapy in conjunction with PD-1 inhibitors (neoadjuvant chemoimmunotherapy) among patients with oropharyngeal and hypopharyngeal squamous cell carcinoma (OPHSCC) and compare its efficacy with neoadjuvant chemotherapy alone. METHODS: We conducted a retrospective analysis using data from patients diagnosed with OPHSCC and treated at the Sun Yat-sen University Cancer Center between September 2012 and August 2022. We included patients who received neoadjuvant chemotherapy alone or combined with PD-1 inhibitors. We assessed the clinical response using the Response Evaluation Criteria in Solid Tumors and evaluated progression-free survival (PFS) and overall survival (OS). RESULTS: Preliminary results demonstrate that neoadjuvant chemoimmunotherapy exhibited robust antitumor activity in OPHSCC, with an impressive overall response rate (ORR) of 81.0%. Complete response and partial response rates were 14.9% and 65.9%, respectively. Notably, neoadjuvant chemoimmunotherapy demonstrated superior PFS and OS to neoadjuvant chemotherapy alone. The 1-year PFS rate was 80.7%, and the 2-year rate was 61.1%. Additionally, the 1-year OS rate reached 92.3%. Finally, a multivariate analysis identified the American Joint Committee on Cancer stage reduction post-treatment as a favorable predictor of PFS. CONCLUSION: Our results underscore the promising potential of neoadjuvant chemoimmunotherapy in enhancing antitumor activity in patients with OPHSCC. The robust ORR, along with improved PFS and OS, supports the utility of this combined approach. These results pave the way for further investigations to validate and refine the application of neoadjuvant chemoimmunotherapy in this challenging clinical context.

Fanconi syndrome induced by the long-term use of tenofovir disoproxil fumarate: a case report and literature review.

We present the case of a woman of 50 years of age who experienced widespread bone pain along with digestive symptoms, including nausea and vomiting. She had been prescribed tenofovir disoproxil fumarate (TDF) tablets for the treatment of hepatitis B. Laboratory testing revealed low circulating phosphorus and potassium concentrations and acidosis. A whole-body bone scan revealed abnormal bone metabolism. Rheumatologic and urologic conditions were ruled out, and therefore TDF-induced Fanconi syndrome (FS) and related bone pain was diagnosed. After the TDF was discontinued, the patient's symptoms and laboratory indices significantly improved. In this manuscript, we highlight the clinical manifestations of and laboratory test results associated with FS and summarize the cases of TDF-induced FS reported on PubMed between 2013 and 2022 to improve understanding of FS.

Body mass index and risk of all-cause mortality among elderly Chinese: An empirical cohort study based on CLHLS data.

The aim of our study was to evaluate the relationship between body mass index (BMI) and all-cause mortality among elderly Chinese. The subjects of our study were a cohort of 13 319 elderly Chinese enrolled between 2008 and 2018. Participants were classified in three groups: underweight (<18.5 kg/m2), normal weight (18.5-24.9 kg/m2), overweight and obese (≥25 kg/m2) according to different BMI levels. Cox proportional-hazards regression model was used to analyze the association between BMI grouping and the risk of mortality among the three groups and each corresponding subgroup. The restricted cubic spline regression was performed to investigate the variation tendency of BMI and mortality in different groups and subgroups. We found that the hazard ratios (HRs) of mortality in the underweight and the normal-weight groups were 1.213 and 1.104, respectively, compared with those in the overweight and obesity groups. HR for mortality decreased as BMI increased, although this phenomenon was not observed as not a linear relationship in all participants. Nonetheless, this nonlinear relationship was significant in type 2 diabetes patients. Among subjects with non-type 2 diabetes, the shape of the negative curve, reflecting the HR for BMI and mortality, decreased when BMI increased. Our findings suggest that an obesity paradox exists in non-type 2 diabetes patients, in which BMI has a nonlinear negative relationship with mortality. Conversely, in type 2 diabetes patients there is a U-shaped association. Obesity may thus be protective for all-cause mortality among non-diabetic older populations.

Epidemiological and transcriptome data identify potential key genes involved in iron overload for type 2 diabetes.

BACKGROUND: Many previous studies have reported the association between iron overload (IO) and type 2 diabetes mellitus (T2DM). However, the underlying molecular mechanism is not clear. METHODS: Epidemiological data from the National Health and Nutrition Examination Survey 2017-2018 (NHANES) was used to systematically explore the association between IO and diabetes. Furthermore, transcriptome data from Gene Expression Omnibus (GEO) were analyzed using bioinformatics methods to explore the underlying functional mechanisms at the molecular level. RESULTS: Data from NHANES showed a "W" shape relationship between serum iron (frozen) and the risk of diabetes (P < 0.001) as well as a "∧" shape correlation between serum unsaturated iron binding capacity (UIBC) and the risk of diabetes (P = 0.007). Furthermore, the serum iron (frozen) was positively associated with fasting plasma glucose and HOMAB (P < 0.05), and UIBC was positively associated with fasting insulin (P < 0.05). Transcriptome data showed that two IO-related genes [Transferrin receptor (TFRC) and Solute carrier family-11 member-2 (SLC11A2)] were down-regulated in T2DM. The correlation analysis showed that expression levels of TFRC and SLC11A2 were significantly and positively correlated with genes involved in insulin secretion (P < 0.05). Protein-protein interaction network analysis showed that TFRC and SLC11A2 interacted with four key genes, including VAMP2, HIF1A, SLC2A1, and RAB11FIP2. CONCLUSION: We found that IO status was associated with increased FPG and aggravated HOMAB, and two IO-related genes (TFRC and SLC11A2) might induce the occurrence of T2DM by influencing insulin secretion, which provides potential therapeutic targets for T2DM patients.

Factors Affecting Radial Artery Occlusion After Right Transradial Artery Catheterization for Coronary Intervention and Procedures.

Objective: To determine the factors influencing proximal radial artery occlusion (PRAO) right radial artery after coronary intervention. Methods: This is a single-center prospective observational study. A total of 460 patients were selected to undergo coronary angiography (CAG) or percutaneous coronary intervention (PCI) via the proximal transradial approach (PTRA) or distal transradial approach (DTRA). The 6F sheath tube were received by all patients. Radial artery ultrasound was performed 1 day before procedure and 1-4 days after procedure. Patients were divided into the PRAO group (42 cases) and the non-PRAO group (418 cases). General clinical data and preoperative radial artery ultrasound indexes of the two groups were compared to analyze related factors leading to PRAO. Results: The total incidence of PRAO was 9.1%, including 3.8% for DTAR and 12.7% for PTRA. The PRAO rate of DTRA was significantly lower than that of PTRA (p < 0.05). Female, low body weight, low body mass index (BMI) and CAG patients were more likely to develop PRAO after procedure (p < 0.05). The internal diameter and cross-sectional area of the distal radial artery and proximal radial artery were smaller in the PRAO group than in the non-PRAO group, and the differences were statistically significant (p < 0.05). Multifactorial model analysis showed that the puncture approach, radial artery diameter and procedure type were predictive factors of PRAO, and the receiver operating characteristic curve showed a good predictive value. Conclusion: A larger radial artery diameter and DTRA may reduce the incidence of PRAO. Preoperative radial artery ultrasound can guide the clinical selection of appropriate arterial sheath and puncture approach.

Biomimetic Nanoparticle with Glutathione Depletion and Amplified ROS Generation Capabilities for Synergistic Chemo-Sonodynamic Therapy in Squamous Cell Carcinomas.

Nanomedicines for combining chemotherapy and sonodynamic therapy (SDT) have enormous potential in squamous cell carcinoma treatment. However, the therapeutic efficacy of noninvasive SDT is severely limited because the generation of reactive oxygen species (ROS) by sonosensitizers is highly dependent on the levels of intracellular excess glutathione (GSH) in the tumor cells. To overcome this barrier, a red blood cell (RBC) membrane-camouflaged nanomedicine consisting of GSH-sensitive polyphosphoester (SS-PPE) and ROS-sensitive polyphosphoester (S-PPE) was designed for the simultaneous delivery of the sonosensitizer hematoporphyrin (HMME) and chemotherapeutic agent docetaxel (DTXL) for effectively enhanced antitumor efficacy. In vitro and in vivo studies demonstrated that HMME-driven ROS generation under ultrasound (US) inhibited SCC7 cell proliferation and accelerated DTXL release to further kill tumor cells via the hydrophobic-hydrophilic transition of the nanoparticle core. Meanwhile, the disulfide bond of SS-PPE effectively consumes GSH to prevent ROS consumption. This biomimetic nanomedicine provides GSH depletion and amplified ROS generation capabilities to achieve a novel synergistic chemo-SDT strategy for squamous cell carcinomas.

Effectiveness of Negative Pressure Wound Therapy of Diabetic Foot Ulcers Using Periplaneta Americana (Kangfuxin Liquid) Irrigation.

This study was to evaluate the efficacy of Periplaneta Americana (Kangfuxin Liquid) relative to normal saline when applied in negative-pressure wound therapy (NPWT) with instillation for facilitating diabetic foot ulcers (DFUs) healing. Eighty patients with Wagner grades 3 or 4 DFUs were enrolled in this retrospective study. Based on the treatment type, patients were equally assigned to either (i) an NPWT with Kangfuxin liquid instillation group (NPWT-K) or (ii) an NPWT with normal saline instillation group (NPWT-I). The primary study outcome was the wound healing rate and Kaplan-Meier survival estimate was used to examine the cumulative wound healing rate, while the secondary outcomes were the amputation rate, inpatient days, duration of antibiotic treatments, reinfection rate, new ulcer formation rate, readmission rate, and changes in the inflammatory markers (such as ESR, CRP, and PCT) and serum growth factors (including VEGF, EGF, and bFGF). The 12-week wound healing rate (31 of 40[77.5%] vs 22 of 40[55.0%], P = .033) and the cumulative wound healing rate was higher in the NPWT-K group than in the NPWT-I group (P = .004). The wound healing time was shorter in the NPWT-K group (55 days [95% CI 50-60]) than in the NPWT-K group (64 days [95% CI 59-69], P = .016). Patients who received NPWT-K had fewer inpatient days and duration of antibiotic treatment and faced lower reinfection and readmission rates (P < .05). After 1 week of treatment, the ESR, CRP, and PCT levels in the blood were lower in the NPWT-K group than in the NPWT-I group (P < .05), while the VEGF, EGF, and bFGF levels in the NPWT-K group were higher than those in the NPWT-I group (P < .001). The present study showed that NPWT with Kangfuxin liquid instillation was effective and showed significantly accelerated DFUs healing. Thus, Kangfuxin liquid is an effective instillation solution for use in the treatment of DFUs with NPWT.

USP7- and PRMT5-dependent G3BP2 stabilization drives de novo lipogenesis and tumorigenesis of HNSC.

GTPase-activating protein-binding protein 2 (G3BP2) is a key stress granule-associated RNA-binding protein responsible for the formation of stress granules (SGs). Hyperactivation of G3BP2 is associated with various pathological conditions, especially cancers. Emerging evidence indicates that post-translational modifications (PTMs) play critical roles in gene transcription, integrate metabolism and immune surveillance. However, how PTMs directly regulate G3BP2 activity is lacking. Here, our analyses identify a novel mechanism that PRMT5-mediated G3BP2-R468me2 enhances the binding to deubiquitinase USP7, which ensures the deubiquitination and stabilization of G3BP2. Mechanistically, USP7- and PRMT5-dependent G3BP2 stabilization consequently guarantee robust ACLY activation, which thereby stimulating de novo lipogenesis and tumorigenesis. More importantly, USP7-induced G3BP2 deubiquitination is attenuated by PRMT5 depletion or inhibition. PRMT5-activity dependent methylation of G3BP2 is required for its deubiquitination and stabilization by USP7. Consistently, G3BP2, PRMT5 and G3BP2 R468me2 protein levels were found positively correlated in clinical patients and associated with poor prognosis. Altogether, these data suggest that PRMT5-USP7-G3BP2 regulatory axis serves as a lipid metabolism reprogramming mechanism in tumorigenesis, and unveil a promising therapeutic target in the metabolic treatment of head and neck squamous carcinoma.

A self-assembling CXCR4-targeted pyroptosis nanotoxin for melanoma therapy.

While immunotherapy has emerged as a promising strategy to treat melanoma, the limited availability of immunotherapeutic agents in tumors due to the immunosuppressive tumor microenvironment dampens its efficacy. Pyroptosis is a gasdermin-mediated programmed necrosis that triggers the inflammatory tumor microenvironment and enhances the efficacy of tumor immunotherapy. Here, we prove that the CXCR4 antagonist T22 peptide specially targeted and became internalized into CXCR4+ melanoma cells. Then we report a self-assembling nanotoxin that can be used to spatiotemporally target CXCR4-expression melanoma cells and enable tunable cellular pyroptosis. Specific activation of caspase 3 signal transduction triggers gasdermin-E-mediated pyroptosis. This nanotoxin induces pyroptotic cell death resulting in enhanced antitumor efficacy and minimized systemic side effects toward melanoma in vivo. This study offers new insights into how to engineer nanotoxins with tunable pyroptosis activity through specifically targeting CXCR4 for biomedical applications.