Retrospective analysis of 71 patients with cutaneous sporotrichosis.

OBJECTIVE: To summarise 71 cases of cutaneous sporotrichosis in Zhejiang over the past 9 years and analyse clinical and epidemiological characteristics. METHODS: This was a retrospective review of patients with cutaneous sporotrichosis attending the Department of Dermatology of the Hangzhou Third People's Hospital between 2013 and 2022. RESULTS: The male-to-female ratio was 1.15:1 among the 71 patients, with a mean age of 55.90 years (±2.02) and an age range of 3 to 94 years. The disease duration was unknown for 17 patients. The intermediate course for the remaining 54 patients lasted 11.90 months, ranging from 1 to 120 months. Thirty-four patients were involved in mixed occupations, 28 were farmers, 4 were housewives, 3 were manufacturing workers, and 2 were carpenters; 23.95% of cases had a history of trauma. The most common clinical manifestation was fixed cutaneous (69.01%), followed by lymphocutaneous (29.58%) and disseminated cutaneous (1.41%). There were 72 affected sites; the upper limbs (69.44%) were affected the most, followed by the face (16.67%) and lower limbs (12.50%). Forty-nine patients showed open lesions (69.01%), 15 showed mixed lesions (21.13%), and seven showed closed lesions (9.86%). Seventy-one patients were confirmed by biopsied tissue or tissue fluid culture. Forty-four patients underwent direct microscopy; of these, 18 (40.91%) were positive and 26 were negative. Molecular analysis confirmed that all fungal strains were Sporothrix globosa. Fifty-nine patients underwent histopathological examination, of whom 18 (18.64%) were positive for periodic acid-Schiff (PAS) staining. Eighteen patients were lost to follow-up; the remaining patients were cured. CONCLUSIONS: Consistent with the epidemiological situation of sporotrichosis in other areas of China, S. globosa is the primary pathogen in the Zhejiang province. The primary clinical form of sporotrichosis is fixed cutaneous. Susceptible subjects are mainly middle-aged and elderly rural populations, and males are affected more than females. Patients with cutaneous sporotrichosis do not commonly have a history of obvious trauma. Direct microscopy is important for the diagnosis of sporotrichosis, and itraconazole is a safe and effective treatment option.

Trichoscopy for early diagnosis and follow-up of pet-related neonatal tinea capitis.

We report infant zigzag hairs as a distinct trichoscopic sign for follow up a case of pet-related newborn tinea capitis due to Microsporum canis. Formation of infant zigzag hairs due to ectothrix M. canis infection may be associated soft neonatal widespread thin hair, which is different from vellus hair and terminal hair. In addition, tinea capitis was further confirmed by transmission electric microscopy and fungal culture. The patient was successfully treated by weekly oral fluconazole (8 mg/kg). Therefore, the handheld dermoscopy is a simple, non-invasive and very inexpensive technique for the diagnosis and follow-up of tinea capitis, especially for infant.

PDGFRß modulates aerobic glycolysis in osteosarcoma HOS cells via the PI3K/AKT/mTOR/c-Myc pathway.

Osteosarcoma is a malignant tumor abundant in vascular tissue, and its rich blood supply may have a significant impact on its metabolic characteristics. PDGFRß is a membrane receptor highly expressed in osteosarcoma cells and vascular wall cells, and its effect on osteosarcoma metabolism needs to be further studied. In this study, we discussed the effect and mechanism of action of PDGFRß on glucose metabolism in human osteosarcoma (HOS) cells. GSEA, Pearson's correlation test, and PPI correlation analysis indicated positive regulation of PDGFRß on aerobic glycolysis in osteosarcoma. The results of qPCR and western blot further confirmed the prediction of bioinformatics. Glucose metabolism experiments proved that PDGF/PDGFRß could effectively promote aerobic glycolysis in osteosarcoma cells. In addition, the mitochondrial membrane potential (ΔΨm) experiment proved that the metabolic change triggered by PDGFRß was not caused by mitochondrial damage. The PI3K pathway inhibitor LY294002, MEK pathway inhibitor U0126, or Warburg effect inhibitor DCA was used to perform western blot and glucose metabolism experiments, and the results showed that PDGFBB/PDGFRß mainly activated the PI3K/AKT/mTOR/c-Myc pathway to promote aerobic glycolysis in osteosarcoma HOS cells. The newly elucidated role of PDGFRß provides a novel metabolic therapeutic target for osteosarcoma.

Efficacy and safety of atezolizumab plus bevacizumab in Korean patients with advanced hepatocellular carcinoma.

BACKGROUND & AIMS: Atezolizumab plus bevacizumab (Ate/Bev) has demonstrated efficacy and safety in patients with advanced hepatocellular carcinoma (HCC) in the phase III trial. Further evaluation is necessary to investigate the safety and efficacy of Ate/Bev in real settings. METHODS: This was a multicentre retrospective analysis. Between May 2020 and February 2021, 138 patients received Ate/Bev as first-line treatment for advanced HCC from 11 institutions. We excluded patients with Child-Pugh B or C and BCLC D stage, and the remaining 121 patients were included in this analysis. RESULTS: According to RECIST 1.1, the objective response and disease control rates were 24.0% and 76.0%. The median follow-up duration was 5.9 months (95% confidence interval [CI], 5.4-6.4), the median progression-free survival (PFS) was 6.5 months (95% CI, 4.1-9.0), and median overall survival (OS) was not reached (95% CI, not available). The most frequent grade 3-4 adverse event was aspartate aminotransferase elevation (10.7%). In the multivariate analyses, AFP increase (P = .037), baseline neutrophil-to-lymphocyte ratio (NLR) ≥ 5 (P = .023), and best response to stable disease or progressive disease (P = .019) were significantly associated with worse PFS. Macrovascular invasion (P = .048) and baseline NLR ≥5 (P < .001) were significantly associated with worse OS. CONCLUSIONS: Ate/Bev showed real-life efficacy and safety in Korean patients with advanced HCC, in line with results from phase III trial. Considering unfavourable survival outcomes of Ate/Bev in patients with elevated NLR, careful assessment of treatment response needs to be performed in this group.

PDGF-BB/PDGFRß promotes epithelial-mesenchymal transition by affecting PI3K/AKT/mTOR-driven aerobic glycolysis in Wilms' tumor G401 cells.

Wilms' tumor (WT) is the most common pediatric renal malignancy. PDGFRß belongs to the type III receptor tyrosine kinase family and is known to be involved in tumor metastasis and angiogenesis. Here, we studied the effect and underlying mechanism of PDGFRß on WT G401 cells. Transwell assay and wound-healing assay were used to detect the effect of PDGFRß on G401 cells invasion and migration. Western blot and immunofluorescence were used to detect the expression of EMT-related genes. The expression of PI3K/AKT/mTOR pathway proteins was detected by Western blot. The relationship between PDGFRß and aerobic glycolysis was studied by assessing the expression of glycolysis-related enzymes detected by qRT-PCR and Western blot. The activity of HK, PK, and LDH was detected by corresponding enzyme activity kits. The concentration of lactic acid and glucose was detected by Lactic Acid Assay Kit and Glucose Assay Kit-glucose oxidase method separately. To investigate the mechanism of PDGFRß in the development of WT, the changes of glucose and lactic acid were analyzed after blocking PI3K pathway, aerobic glycolysis, or PDGFRß. The key enzyme was screened by Western blot and glucose metabolism experiment after HK2, PKM2, and PDK1 were inhibited. The results showed that PDGFRß promoted the EMT process by modulating aerobic glycolysis through PI3K/AKT/mTOR pathway in which PKM2 plays a key role. Therefore, our study of the mechanism of PDGFRß in G401 cells provides a new target for the treatment of WT.

Bedside Diagnosis for Disseminated Deep Dermatophytosis: a Case Series Study.

Deep cutaneous fungal infections including deep dermatophytosis are responsible for significant morbidity and mortality, especially in immunocompromised patients. Variable and longer turnaround time on tissue culture results delay diagnosis. We sought to seek the fast bedside diagnosis for disseminated deep dermatophytosis by direct microscopy using a blunt scalpel or needle aspiration before biopsy. This is a 6-year retrospective review of patients with a diagnosis of disseminated deep dermatophytosis seen at a single tertiary care institution. Trichophyton rubrum was isolated in four patients, and T. mentagrophyte complex in one patient. All the dermatophyte isolates can grow at 37 °C. Microscopy of purulence sampling from intact nodules demonstrated abundant septate hyphae, and also isolation from purulence was concordance with skin tissue culture. Ultrasound-guided sampling from non-eroded can yield purulence, and direct microscopy of purulence may facilitate rapid diagnosis of deep dermatophytosis and serve to prevent disease progression and dissemination.

Markedly prolonged QTc interval in end-stage liver disease and risk of 30-day cardiovascular event after liver transplant.

BACKGROUND AND AIM: The proportional increase of corrected QT interval (QTc) along end-stage liver disease (ESLD) severity may lead to inconsistent outcome reporting if based on conventional threshold of prolonged QTc. We investigated the comprehensive QTc distribution among ESLD patients and assessed the association between QTc > 500 ms, a criterion for diagnosing severe long-QT syndrome, and the 30-day major adverse cardiovascular event (MACE) after liver transplantation (LT) and identified the risk factors for developing QTc > 500 ms. METHODS: Data were collected prospectively from the Asan LT Registry between 2011 and 2018, and outcomes were retrospectively reviewed. Multivariable analysis and propensity score-weighted adjusted odds ratios (ORs) were calculated. Thirty-day MACEs were defined as the composite of cardiovascular mortality, arrhythmias, myocardial infarction, pulmonary thromboembolism, and/or stroke. RESULTS: Of 2579 patients, 194 (7.5%) had QTc > 500 ms (QTc500_Group), and 1105 (42.8%) had prolonged QTc (QTcP_Group), defined as QTc > 470 ms for women and >450 ms for men. The 30-day MACE occurred in 336 (13%) patients. QTc500_Group showed higher 30-day MACE than did those without (20.1% vs 12.5%, P = 0.003), with corresponding adjusted OR of 1.24 (95% CI: 1.06-1.46, P = 0.007). However, QTcP_Group showed comparable 30-day MACE (13.3% vs 12.8% without prolonged QTc, P = 0.764). Significant risk factors for QTc > 500 ms development were advanced liver disease, female sex, hypokalemia, hypocalcemia, high left ventricular end-diastolic volume, and tachycardia. CONCLUSION: Our results revealed that, among ESLD patients, a novel threshold of QTc > 500 ms was associated with post-LT 30-day MACE but not with conventional threshold, indicating that a longer QTc threshold should be considered for this unique patient population.

Tinea capitis in children: A single-institution retrospective review from 2011 to 2019.

Tinea capitis remains a common public health problem worldwide, especially in developing countries. OBJECTIVES: To investigate the changes of the predominant dermatophytes of tinea capitis in children in Hangzhou in recent 9 years. METHODS: The age, gender and pathogen spectrum of 650 children with tinea capitis at the Department of Dermatology, Affiliated Third People's Hospital of Hangzhou, Anhui Medical University from 2011 to 2019 were analysed, and the distribution of pathogens from 1998 to 2000 was compared. RESULTS: Among the 650 cases, 340 cases (48.2%) were males and 310 cases (51.8%) were females. The main population infected with tinea capitis was children aged 0-10 years (620 cases, 95.4%). From 2011 to 2019, the predominant dermatophyte was changed from Trichophyton violaceum (2011) to Trichophyton mentagrophytes complex (2012-2015) and later to Microsporum canis (2016-2019). In the past 9 years, M. canis (250 cases, 38.5%) was the most common dermatophyte and followed by T mentagrophytes complex (209 cases, 32.2%). The dermatophyte spectrum was statistically different between the years 2011 and 2019 (Chi square: χ2  = 69.75, P < .05), and the differences in anthropophilic and zoophilic pathogens between 1989-2000 and 2011-2019 were statistically significant (χ2  = 24.4, P < .05). CONCLUSIONS: Research showed that children diagnosed with tinea capitis were mainly 0-10 years old. With age, the percentage of anthropophilic dermatophytes gradually increased, while the percentage of zoophilic dermatophytes decreased. M. canis was the predominant dermatophyte of tinea capitis in children, followed by T. mentagrophytes complex. The dermatophytes have shifted from anthropophilic to zoophilic dermatophytes in the past two decades.

New Equation for Predicting Pipe Friction Coefficients Using the Statistical Based Entropy Concepts.

In general, this new equation is significant for designing and operating a pipeline to predict flow discharge. In order to predict the flow discharge, accurate determination of the flow loss due to pipe friction is very important. However, existing pipe friction coefficient equations have difficulties in obtaining key variables or those only applicable to pipes with specific conditions. Thus, this study develops a new equation for predicting pipe friction coefficients using statistically based entropy concepts, which are currently being used in various fields. The parameters in the proposed equation can be easily obtained and are easy to estimate. Existing formulas for calculating pipe friction coefficient requires the friction head loss and Reynolds number. Unlike existing formulas, the proposed equation only requires pipe specifications, entropy value and average velocity. The developed equation can predict the friction coefficient by using the well-known entropy, the mean velocity and the pipe specifications. The comparison results with the Nikuradse's experimental data show that the R2 and RMSE values were 0.998 and 0.000366 in smooth pipe, and 0.979 to 0.994 or 0.000399 to 0.000436 in rough pipe, and the discrepancy ratio analysis results show that the accuracy of both results in smooth and rough pipes is very close to zero. The proposed equation will enable the easier estimation of flow rates.

Favus of Scrotum Due to Trichophyton rubrum in Immunocompetent Patients: A Clinical, Mycological and Ultrastructural Study.

PURPOSE: To characterize the clinical and mycological features of favus of scrotum due to Trichophyton rubrum. METHODS: A single-site prospective study was carried out in an outpatient dermatology clinic. Microscopic examination and fungal culture were done using skin scrapings. Scales on the scrotum were stained with PAS and visualized by microscopy, including in vivo reflectance confocal microscopy (RCM). Two strains were analyzed by RAPD typing. Scutular lesions were fixed for scanning electron microscopy (SEM) and transmission electron microscopy (TEM). RESULTS: Cultures of the scale from the scrotum and/or groin in all patients showed a growth of T. rubrum. T. rubrum strains from scrotum and groins in one patient were demonstrated as the same strain by RAPD typing. The average age of patients was 34.1 ± 12.78 years. The mean course was 8.2 ± 5.07 days. All the patients received only topical treatment for 2 weeks without recurrence. Direct smear, calcofluor-white staining and in vivo RCM study of the scrotal favus in patients showed a massive number of septate branching hyphae, while fewer septate hyphae in scales in the groin. Abundant hyphae were found only in the outer layer of the stratum corneum of the scrotum under SEM and TEM with intact bilateral cell walls, and normal nucleus, liposomes and reticulum. Few distorted hyphae structures, cell wall degeneration, degenerated cytoplasm and the autophagy phenomenon could be seen in scales from groin under TEM. CONCLUSIONS: Scrotal favus due to T. rubrum is still a true infection, which most often occurred in immunocompetent patients.

Therapeutic decision-making in elderly patients with acute myeloid leukemia: conventional intensive chemotherapy versus hypomethylating agent therapy.

Standards of care for elderly acute myeloid leukemia (AML) patients unfit for intensive chemotherapy remain undefined. We aimed to compare outcomes of hypomethylating agent (HMA) therapy and intensive chemotherapy (IC) in elderly AML patients and identify the subgroup of patients who are eligible for HMA therapy. We reviewed data on the outcomes of 86 AML patients aged ≥ 65 years, who had undergone treatment between 2010 and 2015. These treatments included IC (25 patients, 29.1%) or therapy using HMA including azacitidine or decitabine (61 patients, 70.9%). The overall response rates were 32 and 19.7%, respectively. Median overall survival (OS) (8 vs. 8 months) and progression-free survival (PFS) (6 vs. 7 months) durations were similar in the two groups. Patients in the HMA group with less than 10% peripheral blood (PB) blasts achieved significantly better OS duration than patients in the IC group (P = 0.043). Patients in the IC group with PB blasts and bone marrow blast of ≥ 10 and ≥ 50%, respectively, achieved better PFS durations than the corresponding patients in the HMA group (P = 0.038). Multivariate analysis identified the hematologic improvement-platelet (HI-P) as an independent prognostic factor for survival in the HMA group (P = 0.005). Our results showed that HMA therapy and IC were associated with similar survival duration in elderly AML patients. This study was noteworthy because it assessed prognostic factors that would help to select elderly patients who could expect actual benefits from undergoing the different therapeutic options available, especially HMA therapy.

High Left Ventricular Filling Pressure on Doppler Echocardiography Is Associated With Graft Failure and Overall Mortality Following Kidney Transplantation.

OBJECTIVE: Although E/e´ is prognostic of mortality in patients with end-stage renal disease (ESED), little is known about the prognostic implications of E/e´ following kidney transplant (KT). The objective of this study was to evaluate whether an elevated E/e´ is associated with graft function, postoperative hemodialysis, and overall mortality in end-stage renal disease patients following KT. DESIGN: A retrospective observational study. SETTING: Tertiary teaching hospital. PARTICIPANTS: In total, 1,045 patients underwent KT at the authors' hospital between January 2006 and December 2013. INTERVENTION: None. MEASUREMENTS AND MAIN RESULTS: Patients were divided into groups with an E/e´<15 or≥15, as assessed by preoperative echocardiography (median time from preoperative assessment of echocardiography to surgery: 37 days [IQR: 16-68 days]). Of 1,045 patients, 821 patients (78.6%) had an E/e´<15, and 224 patients (21.4%) had an E/e´≥15. Multivariate analysis indicated that age (odds ratio [OR]: 1.03; 95% confidence interval [CI]: 1.01-1.04, p = 0.001), diabetes mellitus (OR: 2.7; CI: 1.94-3.83, p<0.001), ß-blocker (OR: 1.4; CI: 1.03-1.95, p = 0.034), left atrial dimension (OR: 1.07; CI: 1.04-1.11, p<0.001), and left ventricular mass index (OR: 1.02; CI: 1.01-1.03, p<0.001) are predictive of E/e´≥15. After adjustment using inverse probability of treatment weighting, E/e´≥15 also was associated independently with postoperative hemodialysis (OR: 2.0; 95% CI: 1.5-2.6, p<0.001), graft failure (OR: 1.7; 95% CI: 1.4-2.2; p<0.001), and overall mortality (hazard ratio [HR]: 3.2; 95% CI: 2.1-4.8, p<0.001). CONCLUSIONS: Preoperative E/e´ is a prognostic indicator of overall mortality in ESRD patients undergoing KT.

Hypoalbuminemia Within Two Postoperative Days Is an Independent Risk Factor for Acute Kidney Injury Following Living Donor Liver Transplantation: A Propensity Score Analysis of 998 Consecutive Patients.

OBJECTIVE: Acute kidney injury is a known major complication of liver transplantation. Previous reports have shown that hypoalbuminemia is associated with an increased risk of acute kidney injury. However, little is known about the relationship between the early postoperative albumin level and acute kidney injury after living donor liver transplantation. The aim of this study was to identify the influence of the postoperative albumin level on acute kidney injury prevalence after living donor liver transplantation. DESIGN: A retrospective analysis. SETTING: A tertiary care university hospital. PATIENTS: Nine hundred and ninety-eighty patients underwent living donor liver transplantation. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We divided the enrolled patients into two groups: group 1 included patients whose postoperative albumin level was less than 3.0 g/dL (n = 522), and group 2 included patients with an albumin level greater than or equal to 3.0 g/dL (n = 476). The prevalence of acute kidney injury, major adverse cardiac events, hospital stay, ICU stay, 30-day mortality, and overall mortality was analyzed using inverse probability of treatment weighting and propensity-score matching (n = 249 pairs) analysis. The prevalence of acute kidney injury was higher in group 1 defined by both Acute Kidney Injury Network (after adjusting for inverse probability of treatment weighting [n = 364; 69.7%] and propensity-score matching [n = 152; 61.0%]) and Risk, Injury, Failure, Loss, and End-stage kidney disease criteria (after adjusting for inverse probability of treatment weighting [n = 419; 80.3%] and propensity-score matching [n = 190; 76.3%]). The overall mortality was higher in group 1 after adjusting for inverse probability of treatment weighting (n = 61; 11.7%) and propensity-score matching (n = 23; 9.2%). The hospital (p < 0.001) and ICU (p = 0.006) stays were significantly prolonged in group 1. Acute kidney injury was associated with ICU stay by the Acute Kidney Injury Network criteria (p = 0.034), and overall mortality was correlated with acute kidney injury by the Risk, Injury, Failure, Loss, and End-stage kidney disease criteria (p = 0.014). CONCLUSIONS: Early postoperative hypoalbuminemia is an independent risk factor for acute kidney injury, and postoperative acute kidney injury is related to postoperative ICU stay and overall mortality after living donor liver transplantation.

Scrotal nodular scabies.

Scabies is a highly infectious parasitic skin disease, The most common lesions are solid and 2-3 mm in diameter (papules). Very few cases will develop into nodular scabies, and microscopy is frequently negative in patients with clinically diagnosed nodular scabies. The accuracy of microscopy depends on the expertise of the operator, particularly in finding burrows and extracting the relevant material.

Negative outcome in cutaneous Mycobacterium marinum infection treated with surgical intervention: Two-case report.

RATIONALE: Mycobacterium marinum (M marinum), a slow-growing nontuberculous mycobacterium (NTM), is widely distributed in aquatic environments. It is a well-known cutaneous pathogen, which causes sporotrichosis-like lesions. PATIENT CONCERNS: In this report, we describe 2 cases of subcutaneous M marinum infection. Both patients underwent several surgical procedures at local hospitals, and despite optimal surgical site healing, new lesions appeared in adjacent sites. DIAGNOSES: Based on NTM culture, identification by gene sequencing, and matrix-assisted laser desorption ionization time-of-flight mass spectrometry, the diagnosis of subcutaneous NTM infection was confirmed. INTERVENTIONS: The patients were treated with oral rifampicin 0.45 g/day and clarithromycin 1 g/day and oral doxycycline hydrochloride capsules (200 mg/day), respectively. OUTCOMES: Both patients were treated for 8 and 5 weeks, respectively, and the lesions healed. LESSONS: Surgical debridement cannot compete with or impede NTM lymphatic spread; antimicrobial therapy is the first choice for the treatment of M marinum infections.

Polyvinylamine and Its Derivative as Effective Carrier for Targeted Delivery of Small RNAs.

Polymeric delivery systems could enable the fast- and low-side-effect transport of various RNA classes. Previously, we demonstrated that polyvinylamine (PVAm), a cationic polymer, transfects many kinds of RNAs with high efficiency and low toxicity both in vitro and in vivo. The modification of poly lactic-co-glycolic acid (PLGA) with cartilage-targeting peptide (CAP) enhances its stiffness and tissue-specific delivery of RNA to overcome the avascular nature of articular cartilage. Here we describe the protocol to use PVAm as an RNA carrier, and further, by modifying PVAm with PLGA and CAP, the corresponding co-polymer could be applied for functional RNA delivery for osteoarthritis treatment.

A Phase II Study About Efficacy and Safety of the Continuous IntraVenous Infusion of Ketamine as Adjuvant to Opioids in Terminally Ill Cancer Patients With Refractory Cancer Pain (CIVIK Trial).

BACKGROUND: Ketamine has been used to control refractory cancer pain as an adjuvant to opioids. We conducted a prospective phase II study to investigate the efficacy and safety of 5-day continuous intravenous infusion (CIVI) of Ketamine in terminally ill cancer patients with refractory cancer pain. METHODS: Hospitalized terminally ill cancer patients with refractory cancer pain were enrolled. Refractory cancer pain was indicated by requirements for 4 or more rescue opioids or pain intensity using numerical rating scale > personalized pain goal (PPG) despite of intravenous morphine equivalent daily dose (IV MEDD) ≥ 120 mg/day. The CIVI of ketamine was increased from .05 mg/kg/hour to .5 mg/kg/hour by .05 every 8 hours if pain intensity exceeded PPG or if number of rescue opioids ≥2 during prior 8 hours was required. The primary end-point was overall pain response rate, which indicates complete response (both rescue opioid ≤3/day and pain intensity ≤ PPG) plus partial response (rescue opioid ≤3/day), without unacceptable toxicities. RESULTS: Among 21 eligible patients enrolled between September 2019 and January 2023, 20 were analyzed. Most pain mechanisms were mixed type (n = 15, 75%), with neuropathic component (n = 17, 85%). The baseline background opioids were IV MEDD 186 mg/24hour (range, 124-592), number of rescue opioids was 6 (IQR, 5-9), and median PPG was 4 (IQR, 3-4). The overall pain response rate was 50% (n = 10) including 40% (n = 8) for complete pain response and 10% (n = 2) for partial pain response. CONCLUSION: This study showed efficacy of gradually increasing CIVI of ketamine for terminally ill cancer patients with refractory cancer pain. CIVI of ketamine could be a useful tool in these patients considering the limited treatment options. (NCT03362073, Initial Release: November 15, 2017).

PDGF-BB/PDGFRß induces tumour angiogenesis via enhancing PKM2 mediated by the PI3K/AKT pathway in Wilms' tumour.

Platelet-derived growth factor receptor-ß (PDGFRß) is a critical type III receptor tyrosine kinase family member, which is involved in Wilms' tumour (WT) metastasis and aerobic glycolysis. The role of PDGFRß in tumour angiogenesis has not been fully elucidated. Here, we examined the effect of PDGFRß on angiogenesis in WT. First, the NCBI database integrated three datasets, GSE2712, GSE11151, and GSE73209, to screen differentially expressed genes. The R language was used to analyse the correlation between PDGFRB and vascular endothelial growth factor (VEGF). The results showed that PDGFRB, encoding PDGFRß, was upregulated in WT, and its level was correlated with VEGFA expression. Next, PDGFRß expression was inhibited by small interfering RNA (siRNA) or activated with the exogenous ligand PDGF-BB. The expression and secretion of the angiogenesis elated factor VEGFA in WT G401 cells were detected using Western blotting and ELISA, respectively. The effects of conditioned medium from G401 cells on endothelial cell viability, migration, invasion, the total length of the tube, and the number of fulcrums were investigated. To further explore the mechanism of PDGFRß in the angiogenesis of WT, the expression of VEGFA was detected after blocking the phosphatidylinositol-3-kinase (PI3K) pathway and inhibiting the expression of PKM2, a key enzyme of glycolysis. The results indicated that PDGFRß regulated the process of tumour angiogenesis through the PI3K/AKT/PKM2 pathway. Therefore, this study provides a novel therapeutic strategy to target PDGFRß and PKM2 to inhibit glycolysis and anti-angiogenesis, thus, developing a new anti-vascular therapy.

Dendrophthoe falcata (L.f.) Ettingsh. and Dendrophthoe pentandra (L.) Miq.: A review of traditional medical uses, phytochemistry, pharmacology, toxicity, and applications.

Dendrophthoe falcata (L.f.) Ettingsh. (DF) and Dendrophthoe pentandra (L.) Miq. (DP) have been traditionally used for the treatment of various ailments, such as cancer, ulcers, asthma, paralysis, skin diseases, tuberculosis, and menstrual troubles, in the ethnomedicinal systems of India and Indonesia. Currently, the chemical structures of 46 compounds have been elucidated from DF and DP, including flavonoids, triterpenes, tannins, steroids, open-chain aliphatics, benzyl derivates, and cyclic chain derivatives. In vitro assays have revealed their anti-tumor and anti-microbial activities. In vivo studies have unraveled their pharmacological properties against tumors, depression, fertility disorders, inflammatory responses, and so on. Additionally, their weak toxicity to rats and brine shrimp, as well as their promising applications for pharmaceutical preparations and combined medication, were also revealed. Herein, we not only recapitulated traditional medical uses, phytochemistry, pharmacology, toxicity, and applications of DF and DP but also discussed current research limitations and future perspectives, which are instructive for those interested in them and are committed to advancing parasitic plants to the Frontier of phytomedicine. We highlighted that DF and DP will become promising medical plants rather than being discarded as notorious pests, provided that more and deeper research is undertaken.