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).

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.

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.

Comparison of prophylactic effects for chemotherapy induced neutropenia between same-day versus next-day administration of pegteograstim (Neurapeg®) in patients treated with chemotherapy regimen composed of day 1 intensive myleosuppressive agent: A randomized phase III clinical trial.

BACKGROUND AND PURPOSE: Administration of pegylated granulocyte-colony-stimulating factor (peg-GCSF) 24 to 72 hours after chemotherapy is usually recommended. Next-day administration (after 24 hours) resulted in fewer duration of grade (Gr) 4 chemotherapy-induced neutropenia (CIN) and decreased severity of CIN than same-day (within 4 hours). However, patients sometimes receive same-day Peg-GCSF for the sake of convenience. In addition, a few prior studies showed that the same-day method is comparable or superior to the next-day method in preventing CIN, especially in chemotherapy regimens that include day 1 myelosuppressive agents. Thus, we aim to verify the hypothesis that same-day administration of pegteograstim, a new formulation of peg-GCSF, is non-inferior to next-day administration in terms of Gr4 CIN duration. METHODS: This study is a randomized, multicenter, open-label, investigator-initiated phase 3 study. Patients with adjuvant/neoadjuvant or first-line palliative chemotherapy comprising intensively myelosuppressive agents on day 1 (mFOLFIRINOX, ECb, EP, FOLFIRI, and FOLFOX) are enrolled. The patients are assigned to the same-day arm or the next-day arm in a 1:1 ratio. The randomizations are stratified according to number of patient CIN risk factors (1 vs ≥2), chemotherapy setting (perioperative vs palliative), and interval (2-week vs 3-week). In the same-day arm, pegteograstim 6 mg is subcutaneously injected within 4 hours after completion of chemotherapy. In the next-day arm, pegetograstim is injected at 24 to 36 hours post-chemotherapy. A complete blood count test is performed daily from day 5 to 9 during the cycle 1. The primary endpoint is duration of Gr4 CIN (cycle 1), and secondary endpoints include incidence of Gr 3 to 4 CIN (cycle 1), severity of CIN (cycle 1), time to recovery absolute neutrophil count 1000/µL (cycle 1), incidence of febrile neutropenia, incidence of CIN-related dose delay, and dose intensity. In order to verify non-inferiority of 0.6 days, we estimated a significance level of 5%, power of 80%, and drop-out rate of 15%. This results in the need for a total of 160 patients, 80 in each group.

[Scientific basis of acupuncture on mesenchymal stem cells for treating ischemic stroke].

The scientific basis of acupuncture on mesenchymal stem cells (MSCs) for treating ischemic stroke (IS) is discussed. MSCs transplantation has great potential for the treatment of tissue damage caused by early stage inflammatory cascade reactions of IS, but its actual transformation is limited by various factors. How to improve the homing efficiency of MSCs is the primary issue to enhance its efficacy. As such, the possible mechanisms of acupuncture and MSCs transplantation in inhibiting inflammatory cascade reactions induced by IS are explored by reviewing literature, and a hypothesis that acupuncture could promote the secretion of stromal cell-derived factor-1α (SDF-1α) from ischemic foci to regulate SDF-1α/CXC chemokine receptor 4 (CXCR4) axis, thereby improving the homing efficiency of MSCs transplantation, exerting its neuroprotective function, and improving the bed transformation ability, is proposed.

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.

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.

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.

Multidisciplinary Treatment Strategy for Early Colon Cancer: A Review-An English Version.

Treatment for early colon cancer has progressed rapidly, with endoscopic resection and minimally invasive surgery. It is important to select patients without risk of lymph node metastasis before deciding on endoscopic resection for early colon cancer treatment. Pathological risk factors include histologic grade of cancer cell differentiation, lymphovascular invasion, perineural invasion, tumor budding, and deep submucosal invasion. These risk factors for predicting lymph node metastasis are crucial for determining the treatment strategy of endoscopic excision and radical resection for early colon cancer. A multidisciplinary approach is emphasized to establish a treatment strategy for early colon cancer to minimize the risk of complications and obtain excellent oncologic outcomes by selecting an appropriate treatment optimized for the patient's stage and condition. Therefore, we aimed to review the optimal multidisciplinary treatment strategies, including endoscopy and surgery, for early colon cancer.

Real-world experience of safety and effectiveness of regorafenib for treatment of metastatic colorectal cancer, advanced gastrointestinal stromal tumors, and hepatocellular carcinoma: a post-marketing surveillance study in Korea.

Purpose: This regulatory post-marketing surveillance (PMS) study was performed to evaluate the safety and effectiveness of regorafenib on Korean patients with colorectal cancer (CRC), gastrointestinal stromal tumors (GIST), and hepatocellular carcinoma (HCC) in a real-world clinical setting. Methods: This PMS was conducted as a multi-center, prospective, observational study at 34 centers in Korea from August 2013 to August 2019. The primary objective was to evaluate the safety of regorafenib in real-world practice, with the secondary objective to investigate its effectiveness, including its overall response rate (ORR), progression-free survival (PFS), and overall survival (OS). Results: In total, 301 patients were included in the analysis (254 patients with CRC, 14 patients with GIST, and 33 patients with HCC). The incidence rates of adverse events (AEs) were 85.0%, 78.6%, and 81.8% in patients with CRC, GIST, and HCC, respectively. The most frequent AE related to regorafenib in the three cancer types was palmar-plantar erythrodysesthesia syndrome (PPES). The ORRs of patients with CRC, GIST, and HCC were 4.7%, 0%, and 41.4%, respectively. The median PFS and OS were 2.1 and 6.1 months for CRC, respectively; 9.2 and 16.4 months for GIST, respectively; and 5.5 months and not estimated (NE) for HCC, respectively. Patients who experienced a dose modification or discontinuation of regorafenib showed significantly shorter median PFS and OS (2.2 vs. 2.6 months, respectively, P = 0.0335 for PFS; 5.3 vs. 8.5 months, respectively, P = 0.0010 for OS). Conclusion: This PMS study, which is the largest surveillance study of CRC in Korea, found no newly identified safety concerns for patients who received regorafenib in the real-world setting. Additionally, the results of this study were consisted with those previously reported in phase III trials.

Chromoblastomycosis: A case series from Eastern China.

Chromoblastomycosis (CBM) is a chronic fungal infection of the cutaneous and subcutaneous tissues caused by brown pigmented fungi. Fonsecaea monophora is one of the most common pathogens of CBM in China. Most formal cases have been reported from Southern China, however, the infection is not uncommon in Eastern China where very few case series are available. To describe the clinical aspects of CBM, we report a series of 11 cases between 2018 and 2021 at a single medical center in Eastern China. The patients were predominately male (n = 9) and the disease duration ranged from 3 months to 20 years. Plaque type lesions were the most common clinical manifestations. There were 7 cases of mild forms and 3 cases of severe forms. Among the 3 severe cases, one case gave up treatment due to economic poverty; one case did not respond to a 1-year systemic treatmen; one case was cured by combination therapy of 10 months. Other cases were cured by treatment with antifungal agents. All cases of direct mycological examination were positive. All isolates were identified by morphology and sequencing of the the ITS regions of ribosomal DNA, Ten were F. monophora and 1 was Cladophialophora carrionii. All cases had been evaluated at other clinics, where 8 cases were misdiagnosed as other diseases. As a neglected tropical disease (NTD), CBM is still a major challenge in the field of dermatology, especially in its severe clinical forms. As an effective and simple diagnostic method of CBM, direct microscopic examination should be further promoted in rural hospitals.

Transfer RNAs-derived small RNAs and their application potential in multiple diseases.

The role of tRNAs is best known as adapter components of translational machinery. According to the central dogma of molecular biology, DNA is transcribed to RNA and in turn is translated into proteins, in which tRNA outstands by its role of the cellular courier. Recent studies have led to the revision of the canonical function of transfer RNAs (tRNAs), which indicates that tRNAs also serve as a source for short non-coding RNAs called tRNA-derived small RNAs (tsRNAs). tsRNAs play key roles in cellular processes by modulating complicated regulatory networks beyond translation and are widely involved in multiple diseases. Herein, the biogenesis and classification of tsRNAs were firstly clarified. tsRNAs are generated from pre-tRNAs or mature tRNAs and are classified into tRNA-derived fragments (tRFs) and tRNA halves (tiRNA). The tRFs include five types according to the incision loci: tRF-1, tRF-2, tRF-3, tRF-5 and i-tRF which contain 3' tiRNA and 5' tiRNA. The functions of tsRNAs and their regulation mechanisms involved in disease processes are systematically summarized as well. The mechanisms can elaborate on the specific regulation of tsRNAs. In conclusion, the current research suggests that tsRNAs are promising targets for modulating pathological processes, such as breast cancer, ischemic stroke, respiratory syncytial virus, osteoporosis and so on, and maintain vital clinical implications in diagnosis and therapeutics of various diseases.

Prospective comparative analysis of noninvasive body temperature monitoring using zero heat flux technology (SpotOn sensor) compared with esophageal temperature monitoring during pediatric surgery.

Maintaining body temperature in pediatric patients is critical, but it is often difficult to use currently accepted core temperature measurement methods. Several studies have validated the use of the SpotOn sensor for measuring core temperature in adults, but studies on pediatric patients are still lacking. The aim of this study was to investigate the accuracy of the SpotOn sensor compared with that of esophageal temperature measurement in pediatric patients intraoperatively. Children aged 1-8 years with American Society of Anesthesiology Physical Condition Classification I or II scheduled to undergo elective ear surgery for at least 30 min under general anesthesia were enrolled. Body core temperature was measured every 15 min after induction till the end of anesthesia with an esophageal probe, axillary probe, and SpotOn sensor. We included 49 patients, providing a total 466 paired measurements. Analysis of Pearson rank correlation between SpotOn and esophageal pairs showed a correlation coefficient (r) of 0.93 (95% confidence interval [CI] 0.92-0.94). Analysis of Pearson rank correlation between esophageal and axillary pairs gave a correlation coefficient (r) of 0.89 (95% CI 0.87-0.91). Between the SpotOn and esophageal groups, Bland-Altman analysis revealed a bias (SD, 95% limits of agreement) of -0.07 (0.17 [-0.41-0.28]). Between the esophageal and axillary groups, Bland-Altman analysis showed a bias (SD, 95% limits of agreement) of 0.45 (0.22 [0-0.89]). In pediatric patients during surgery, the SpotOn sensor showed high correlation and agreement with the esophageal probe, which is a representative core temperature measurement method.

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.

Influence of Dichloroacetate on Wilms'Tumor in vitro.

OBJECTIVE: To investigate the effect of dichloroacetate (DCA) on Wilms' tumor (WT) G401 cells. METHODS: CCK-8 assay was used to detect the influence of DCA on G401 cells viability and 10 mmol/L DCA was selected for subsequent experiments. The expression of glycolysis-related enzymes, such as hexokinase 2 (HK2), pyruvate kinase M2 (PKM2), lactic acid dehydrogenase A (LDHA), pyruvate dehydrogenase kinase 1 (PDK1), and pyruvate dehydrogenase (PDH), were detected by qRT-PCR and western blot. The extracellular lactic acid and glucose concentrations were measured by the lactic acid assay kit and glucose oxidase method kit respectively. Flow cytometry was used to detect the effect of DCA on G401 cells apoptosis. The invasion and migration ability of G401 cells were detected by Transwell assay and wound-healing assay. RESULTS: The results showed that DCA reduced glycolysis-related enzymes expression, inhibited lactic acid production, and glucose consumption. DCA also suppressed cells growth, induced cells apoptosis and inhibited cells invasion and migration. CONCLUSION: Inhibition of aerobic glycolysis by DCA can reduce the viability of G401 cells, promote cells apoptosis and inhibit cells invasion and migration. Therefore, aerobic glycolysis may be a potential therapeutic target for Wilms' tumor.

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.

Serious acid-base disorder or life-threatening arrhythmia in patients with ABO-incompatible liver transplantation who received therapeutic plasma exchange - A report of two cases.

BACKGROUND: Excessive citrate load during therapeutic plasma exchange (TPE) can cause metabolic alkalosis with compensatory hypercarbia and electrolyte disturbances. If TPE is required immediately before ABO-incompatible (ABOi) liver transplant (LT) surgery, metabolic derangement and severe electrolyte disturbance could worsen during LT anesthesia. CASE: We report two ABOi LT cases who received TPE on the day of surgery because isoagglutinin titers did not be dropped below 1:8. One case had a surprisingly high metabolic alkalosis with a pH of 7.73 immediately after tracheal intubation because of hyperventilation during mask bagging. The other experienced sudden ventricular tachycardia and blood pressure drop after surgical incision accompanied with severe hypokalemia of 1.8 mmol/L despite supplementation with potassium. CONCLUSIONS: Special attention should be paid to patients who just completed TPE the operative day morning as they are vulnerable to severe acid-base disturbances and life-threatening ventricular arrhythmias in ABOi LT.

Intraoperative lactic acid concentration during liver transplantation and cutoff values to predict early mortality: a retrospective analysis of 3,338 cases.

BACKGROUND: We aimed to explore the distribution of intraoperative lactic acid (LA) level during liver transplantation (LT) and determine the optimal cutoff values to predict post-LT 30-day and 90-day mortality. METHODS: Intraoperative LA data from 3,338 patients were collected between 2008 to 2019 and all-cause mortalities within 30 and 90 days were retrospectively reviewed. Of the three LA levels measured during preanhepatic, anhepatic, and neohepatic phase of LT, the peak LA level was selected to explore the distribution and predict early post-LT mortality. To determine the best cutoff values of LA, we used a classification and regression tree algorithm and maximally selected rank statistics with the smallest P value. RESULTS: The median intraoperative LA level was 4.4 mmol/L (range: 0.5-34.7, interquartile range: 3.0-6.2 mmol/L). Of the 3,338 patients, 1,884 (56.4%) had LA levels > 4.0 mmol/L and 188 (5.6%) had LA levels > 10 mmol/L. Patients with LA levels > 16.7 mmol/L and 13.5-16.7 mmol/L showed significantly higher 30-day mortality rates of 58.3% and 21.2%, respectively. For the prediction of the 90-day mortality, 8.4 mmol/L of intraoperative LA was the best cutoff value. CONCLUSIONS: Approximately 6% of the LT recipients showed intraoperative hyperlactatemia of > 10 mmol/L during LT, and those with LA > 8.4 mmol/L were associated with significantly higher early post-LT mortality.

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.