Low-Temperature Plasma Radiofrequency Ablation for Congenital Epiglottic Cysts.

Objectives: Congenital epiglottic cysts are rare disorders of the larynx with symptoms such as laryngeal stridor and inspiratory dyspnea and are life-threatening in severe cases. This study aimed to investigate the usefulness of low-temperature plasma radiofrequency ablation for congenital epiglottic cysts and provide a reference for clinicians to develop treatment options. Methods: The clinical data of children (n = 7, 4 males and 3 females) with congenital epiglottic cysts, who were admitted to the Second Affiliated Hospital of Wenzhou Medical University and Yuying Children's Hospital from March 2018 to March 2023, were analyzed retrospectively. Following preoperative examinations, all patients underwent low-temperature plasma radiofrequency ablation under general anesthesia, and the curative effect was evaluated. Following surgery, regular patient follow-up examinations were conducted to monitor recurrence. Results: The age at the time of operation ranged from 1 day to 99 days, with an average of 37.57 ± 35.01 days. The surgical procedure was successfully completed in all the children; dyspnea disappeared and no surgical complications were observed. In addition, during the postoperative follow-up period of 6 months to 5 years, recurrence was not observed. Conclusions: Low-temperature plasma radiofrequency ablation is a safe and effective procedure for treating congenital epiglottic cysts and deserves clinical application and promotion.

Branched glycopolymer prodrug-derived nanoassembly combined with a STING agonist activates an immuno-supportive status to boost anti-PD-L1 antibody therapy.

Despite the great potential of anti-PD-L1 antibodies for immunotherapy, their low response rate due to an immunosuppressive tumor microenvironment has hampered their application. To address this issue, we constructed a cell membrane-coated nanosystem (mB4S) to reverse an immunosuppressive microenvironment to an immuno-supportive one for strengthening the anti-tumor effect. In this system, Epirubicin (EPI) as an immunogenic cell death (ICD) inducer was coupled to a branched glycopolymer via hydrazone bonds and diABZI as a stimulator of interferon genes (STING) agonist was encapsulated into mB4S. After internalization of mB4S, EPI was acidic-responsively released to induce ICD, which was characterized by an increased level of calreticulin (CRT) exposure and enhanced ATP secretion. Meanwhile, diABZI effectively activated the STING pathway. Treatment with mB4S in combination with an anti-PD-L1 antibody elicited potent immune responses by increasing the ratio of matured dendritic cells (DCs) and CD8+ T cells, promoting cytokines secretion, up-regulating M1-like tumor-associated macrophages (TAMs) and down-regulating immunosuppressive myeloid-derived suppressor cells (MDSCs). Therefore, this nanosystem for co-delivery of an ICD inducer and a STING agonist achieved promotion of DCs maturation and CD8+ T cells infiltration, creating an immuno-supportive microenvironment, thus potentiating the therapy effect of the anti-PD-L1 antibody in both 4T1 breast and CT26 colon tumor mice.

Morphology and optical properties of Au-Ag hybrid nanoparticles regulation and its ultra-sensitive SERS immunoassay detection in carbohydrate antigen 19-9.

The development of an ultra-sensitive detection method for carbohydrate antigen 19-9 (CA19-9) is very important for the early diagnosis of pancreatic cancer. In this work, we developed a new strategy to achieve a variety of Au-Ag hybrid nanoparticles from janus to core-satellite which is controlled by the volume of AgNO3 and the concentration of benzimidazolecarboxylic acid (MBIA). With the volume of AgNO3 increased, Au-Ag hybrid nanoparticles changed from janus to core-satellite and the characteristic absorption peak showed two opposite trends. The size and number of Ag islands were determined by the concentration of MBIA. Au-Ag core-satellites nanoparticles with a large number of small-sized Ag have the highest SERS intensity. Then we used them as SERS nanotags and Au-Polystyrene nanospheres modified by captured anti-CA19-9 antibody as solid substrates to realize the ultra-sensitive detection of CA19-9 with a low limit of detection of 1.25 × 10-6 IU/mL and a wide linear range of 1.00 × 10-5 -1.00 × 104 IU/mL. This work not only demonstrates that MBIA and AgNO3 were the key factors in the growth of Au-Ag hybrid nanoparticles from 2D to 3D structure but also supplies an ultra-sensitive detection method for CA19-9 which has a potential practicability in the clinical early diagnoses of pancreatic cancer.

Hypoxia-inducible factor-2α promotes fibrosis in non-alcoholic fatty liver disease by enhancing glutamine catabolism and inhibiting yes-associated protein phosphorylation in hepatic stellate cells.

Non-alcoholic fatty liver disease (NAFLD) has a high global prevalence and affects approximately one-third of adults, owing to high-fat dietary habits and a sedentary lifestyle. The role of hypoxia-inducible factor 2α (HIF-2α) in NAFLD progression remains unknown. This study aimed to investigate the effects of chronic hypoxia on NAFLD progression by examining the role of hypoxia-inducible factor 2α (HIF-2α) activation and that of hepatic stellate cell (HSC)-derived myofibroblasts through glutaminolysis. We hypothesised that hypoxia exacerbates NAFLD by promoting HIF-2α upregulation and inhibiting phosphorylated yes-associated protein (YAP), and that increasing YAP expression enhances HSC-derived myofibroblasts. We studied patients with NAFLD living at high altitudes, as well as animal models and cultured cells. The results revealed significant increases in HSC-derived myofibroblasts and collagen accumulation caused by HIF-2α and YAP upregulation, both in patients and in a mouse model for hypoxia and NAFLD. HIF-2α and HIF-2α-dependent YAP downregulation reduced HSC activation and myofibroblast levels in persistent chronic hypoxia. Furthermore, hypoxia-induced HIF-2α upregulation promoted YAP and inhibited YAP phosphorylation, leading to glutaminase 1 (GLS1), SLC38A1, α-SMA, and Collagen-1 overexpression. Additionally, hypoxia restored mitochondrial adenosine triphosphate production and reactive oxygen species (ROS) overproduction. Thus, chronic hypoxia-induced HIF-2α activation enhances fibrosis and NAFLD progression by restoring mitochondrial ROS production and glutaminase-1-induced glutaminolysis, which is mediated through the inhibition of YAP phosphorylation and increased YAP nuclear translocation. In summary, HIF-2α plays a pivotal role in NAFLD progression during chronic hypoxia.

Erratum: ß-elemene promotes the senescence of glioma cells through regulating YAP-CDK6 signaling.

[This corrects the article on p. 370 in vol. 11, PMID: 33575077.].

Serum CXCL13 level is related to treatment response and predicts disease prognosis in Waldenström macroglobulinemia.

Waldenström macroglobulinemia (WM) is a type of B-cell lymphoma that produces IgM. Our study aimed to investigate the role of CXCL13, a chemokine essential for B lymphocytes, in the evaluation of treatment response and prognosis in WM. We collected serum samples and clinical data from 72 WM patients, with 69 patients receiving systemic therapy and 3 patients opting not to receive treatment. Serum CXCL13 levels at baseline and after six months of treatments were measured by enzyme-linked immunosorbent assay. The median serum level of CXCL13 was 1 539.2 pg/ml (range 10.0-21 389.9) at baseline and significantly decreased to 123.1 pg/ml (range 0.0-6 741.5) after 6 months of treatments. At baseline, higher CXCL13 levels were associated with lower hemoglobin levels (p = 0.001), higher ß2-microglobulin levels (p = 0.001), lower albumin levels (p = 0.046), and higher IPSS-WM scores (p = 0.013). After 6 months of treatment, patients who achieved PR/VGPR had significantly lower CXCL13 levels compared to those with SD (70.2 pg/ml vs 798.6 pg/ml, p = 0.002). The median follow-up period was 40 months (range 4.2-188). Eight patients died during the follow-up period. Overall survival differed based on CXCL13 levels. When grouped by baseline CXCL13 levels, the median OS was 60.0 months in patients with serum CXCL13 > 2 000 pg/ml, while it was not reached in patients with low CXCL13 levels (p < 0.001). Based on CXCL13 levels after the treatments, the median OS was 74.0 months in patients with serum CXCL13 > 200 pg/ml, while it was not reached in patients with CXCL13 ≤ 200 pg/ml. In a subgroup of 28 patients with a series of serum samples, the increase of serum CXCL13 level was associated with disease progression or the start of next-line therapy (p < 0.001). Our study concludes that serum CXCL13 levels decrease in WM patients treated with various regimens and correlate with treatment response. Detecting serum CXCL13 at baseline or after treatment help in predicting prognosis.

Phase 2 study using low dose cytarabine for adult patients with newly diagnosed Langerhans cell histiocytosis.

Langerhans cell histiocytosis (LCH) lacks a standardized first-line therapy. This single-center, phase 2 prospective study (NCT04121819) enrolled 61 newly diagnosed adult LCH patients with multisystem or multifocal single system disease from October 2019 to June 2022. Subcutaneous cytarabine (100 mg/m2 for 5 days) was administered in 35-day cycles for 12 total cycles. The primary endpoint was event-free survival (EFS). The median age was 33 years (range 18-66). Twelve patients (19.7%) had liver involvement, of which 2 also had spleen involvement. Among 43 patients undergoing next-generation sequencing, BRAF alterations (44.2%) were most frequent, followed by TP53 (16.3%), MAP2K1 (14.0%) and IDH2 (11.6%). MAPK pathway alterations occurred in 28 patients (65.1%). The overall response rate was 93.4%, with 20 (32.7%) achieving complete response and 37 (60.7%) partial response. After a median 30 months follow-up, 21 (34.4%) relapsed without deaths. Estimated 3-year OS and EFS were 100.0% and 58.5%, respectively. Multivariate analysis identified ≥3 involved organs (P = 0.007; HR 3.937, 95% CI: 1.456-9.804) and baseline lung involvement (P = 0.028; HR 2.976, 95% CI: 1.126-7.874) as poor prognostic factors for EFS. The most common grade 3-4 toxicities were neutropenia (27.9%), thrombocytopenia (1.6%), and nausea (1.6%). In conclusion, cytarabine monotherapy is an effective and safe regimen for newly diagnosed adults, while baseline lung or ≥3 involved organs confers poor prognosis.

Germline defects of familial hemophagocytic lymphohistiocytosis-related genes presenting as adult-onset peripheral T-cell lymphoma.

Germline mutations in genes involved in perforin-granzyme-mediated cytotoxicity such as PRF1, UNC13D, STX11, and STXBP2 were known to cause familial hemophagocytic lymphohistiocytosis (FHL). In this study, we reported a unique group of 3 patients with germline mutations of UNC13D and STX11 genes and presented as adult-onset peripheral T-cell lymphoma (PTCL) with cytotoxic T-cell phenotype and atypical lymphoma presentations. CD107a degranulation assay and NK-cell activity analysis demonstrated impaired cytotoxic function of the NK/T-cells of the patients with FHL-related mutations. Gene expression profile study revealed that up-regulated genes of the cytotoxic T-cells were enriched in autoimmune-related pathways. It was possible that impaired cytotoxic lymphocyte-mediated immune surveillance and autoantigen stimulation may both participate in PTCL oncogenesis. Germline defects of FLH-related genes may represent a novel predisposing factor for PTCLs.

Core-shell structured carbon dots with up-conversion fluorescence and photo-triggered nitric oxide-releasing properties.

Cancer-targeted nanotechnology has a new trend in the design and preparation of new materials with functions for imaging and therapeutic applications simultaneously. As a new type of carbon nanomaterial, the inherent core-shell structured carbon dots (CDs) can be designed to provide a modular nanoplatform for integration of bioimaging and therapeutic capabilities. Here, core-shell structured CDs are designed and synthesized from levofloxacin and arginine and named Arg-CDs, in which levofloxacin-derived chromophores with up-conversion fluorescence are densely packed into the carbon core while guanidine groups are located on the shell, providing nitric oxide (NO) for photodynamic therapy of tumors. Moreover, the chromophores in the carbon core irradiated by visible LED light generate large amounts of reactive oxygen species (ROSs) that will oxidize the guanidine groups located on the shell of the Arg-CDs and further increase the NO releasing capacity remarkably. The as-synthesized Arg-CDs show excellent biocompatibility, bright up-conversion fluorescence, and a light-controlled ROS & NO releasing ability, which can be a potential light-modulated nanoplatform to integrate bioimaging and therapeutic functionalities.

Personalized differential expression analysis in triple-negative breast cancer.

Identification of individual-level differentially expressed genes (DEGs) is a pre-step for the analysis of disease-specific biological mechanisms and precision medicine. Previous algorithms cannot balance accuracy and sufficient statistical power. Herein, RankCompV2, designed for identifying population-level DEGs based on relative expression orderings, was adjusted to identify individual-level DEGs. Furthermore, an optimized version of individual-level RankCompV2, named as RankCompV2.1, was designed based on the assumption that the rank positions of genes and relative rank differences of gene pairs would influence the identification of individual-level DEGs. In comparison to other individualized analysis algorithms, RankCompV2.1 performed better on statistical power, computational efficiency, and acquired coequal accuracy in both simulation and real paired cancer-normal data from ten cancer types. Besides, single sample GSEA and Gene Set Variation Analysis analysis showed that pathways enriched with up-regulated and down-regulated genes presented higher and lower enrichment scores, respectively. Furthermore, we identified 16 genes that were universally deregulated in 966 triple-negative breast cancer (TNBC) samples and interacted with Food and Drug Administration (FDA)-approved drugs or antineoplastic agents, indicating notable therapeutic targets for TNBC. In addition, we also identified genes with highly variable deregulation status and used these genes to cluster TNBC samples into three subgroups with different prognoses. The subgroup with the poorest outcome was characterized by down-regulated immune-regulated pathways, signal transduction pathways, and apoptosis-related pathways. Protein-protein interaction network analysis revealed that OAS family genes may be promising drug targets to activate tumor immunity in this subgroup. In conclusion, RankCompV2.1 is capable of identifying individual-level DEGs with high accuracy and statistical power, analyzing mechanisms of carcinogenesis and exploring therapeutic strategy.

Enzyme-Responsive Branched Glycopolymer-Based Nanoassembly for Co-Delivery of Paclitaxel and Akt Inhibitor toward Synergistic Therapy of Gastric Cancer.

Combined chemotherapy and targeted therapy holds immense potential in the management of advanced gastric cancer (GC). GC tissues exhibit an elevated expression level of protein kinase B (AKT), which contributes to disease progression and poor chemotherapeutic responsiveness. Inhibition of AKT expression through an AKT inhibitor, capivasertib (CAP), to enhance cytotoxicity of paclitaxel (PTX) toward GC cells is demonstrated in this study. A cathepsin B-responsive polymeric nanoparticle prodrug system is employed for co-delivery of PTX and CAP, resulting in a polymeric nano-drug BPGP@CAP. The release of PTX and CAP is triggered in an environment with overexpressed cathepsin B upon lysosomal uptake of BPGP@CAP. A synergistic therapeutic effect of PTX and CAP on killing GC cells is confirmed by in vitro and in vivo experiments. Mechanistic investigations suggested that CAP may inhibit AKT expression, leading to suppression of the phosphoinositide 3-kinase (PI3K)/AKT signaling pathway. Encouragingly, CAP can synergize with PTX to exert potent antitumor effects against GC after they are co-delivered via a polymeric drug delivery system, and this delivery system helped reduce their toxic side effects, which provides an effective therapeutic strategy for treating GC.

Surgical treatment of atlantoaxial dysplasia and scoliosis in spondyloepiphyseal dysplasia congenita: A case report.

BACKGROUND: Spondyloepiphyseal dysplasia congenita (SEDC) is a rare autosomal dominant hereditary disease caused by COL2A1 mutations. SEDC primarily involves the skeletal system, with typical clinical manifestations, including short stature, hip dysplasia, and spinal deformity. Due to the low incidence of SEDC, there are only a few case reports regarding the surgical treatment of SEDC complicated with spinal deformities. CASE SUMMARY: We report a case of a 16-year-old male patient with SEDC. He presented with typical short stature, atlantoaxial dysplasia, scoliosis, and hip dysplasia. Cervical magnetic resonance imaging showed spinal canal stenosis at the atlas level and cervical spinal cord compression with myelopathy. The scoliosis was a right thoracic curve with a Cobb angle of 65°. He underwent atlantoaxial reduction, decompression, and internal fixation from C1-C2 to relieve cervical myelopathy. Three months after cervical surgery, posterior correction surgery for scoliosis was performed from T3 to L4. Scoliosis was corrected from 66° to 8° and remained stable at 2-year follow-up. CONCLUSION: This is the first case report of a patient with SEDC who successfully underwent surgery for atlantoaxial dysplasia and scoliosis. The study provides an important reference for the surgical treatment of SEDC complicated with spinal deformities.

Preoperative inflammation and nutrition-based comprehensive biomarker for predicting prognosis in resectable colorectal cancer.

Background: Colorectal cancer (CRC) remains a major global health concern, with significant morbidity and mortality rates. In this study, we aimed to develop a comprehensive blood indicator based on systemic inflammation and nutritional condition to predict the prognosis of resectable CRC patients. Methods: A retrospective cohort of 210 CRC patients who underwent radical resection at the First Affiliated Hospital of Chongqing Medical University, China, between January 2015 and December 2017, was included in the analysis. Baseline characteristics, preoperative blood markers, including neutrophil count, monocyte count, lymphocyte count, platelets, albumin, and CEA were retrospectively reviewed. Various blood indicators, such as NLR, PLR, MLR, SIRI and OPNI were calculated. The least absolute shrinkage and selection operator (LASSO) method was employed to select indicators to establish a novel comprehensive biomarker (named PSI). Kaplan-Meier survival curves and log-rank tests were used to evaluate the prognostic impact of preoperative OPNI, SIRI, and PSI. Univariate and multivariate Cox regression model were conducted to identify independent prognostic factors for CRC. The receiver operating characteristic (ROC) method assessed the predictive ability of PSI, stage, OPNI, and SIRI. Results: Patients with higher preoperative OPNI and lower SIRI values had significantly better overall survival (OS). PSI was identified as an independent prognostic factor for OS in both univariate and multivariate analysis. Patients with medium (28.3-43.4) and high (>43.4) PSI scores exhibited superior OS compared to those with low (≤ 28.3) PSI scores. PSI showed higher predictive ability (AUC: 0.734) than individual indicators alone (OPNI: 0.721, SIRI: 0.645, stage: 0.635). Conclusion: The novel indicator, PSI, based on preoperative SIRI and OPNI, demonstrated significant prognostic value for resectable CRC patients. PSI outperformed individual indicators and could serve as a reliable tool for prognostic evaluation in CRC patients.

A Voice Disease Detection Method Based on MFCCs and Shallow CNN.

The incidence rate of voice diseases is increasing year by year. The use of software for remote diagnosis is a technical development trend and has important practical value. Among voice diseases, common diseases that cause hoarseness include spasmodic dysphonia, vocal cord paralysis, vocal nodule, and vocal cord polyp. This paper presents a voice disease detection method that can be applied in a wide range of clinical. We cooperated with Xiangya Hospital of Central South University to collect voice samples from 352 different patients. The Mel Frequency Cepstrum Coefficient (MFCC) parameters are extracted as input features to describe the voice in the form of data. An innovative model combining MFCC parameters and single convolution layer CNN is proposed for fast calculation and classification. The highest accuracy we achieved was 92%, it is fully ahead of the original research results and internationally advanced. And we use advanced voice function assessment databases (AVFAD) to evaluate the generalization ability of the method we proposed, which achieved an accuracy rate of 98%. Experiments on clinical and standard datasets show that for the pathological detection of voice diseases, our method has greatly improved in accuracy and computational efficiency.

Clinical and molecular epidemiology of carbapenem-resistant Enterobacteriaceae in pediatric inpatients in South China.

IMPORTANCE: This study assessed the clinical and molecular epidemiology of carbapenem-resistant Enterobacteriaceae in pediatric inpatients at three hospitals in South China by means of screening stool samples for carbapenem-resistant genes and a nested case-control study to determine risk factors for carriage of carbapenem-resistant Enterobacteriaceae. Of 4,033 fecal samples screened, 158 (3.92%) were positive for CRE, including Escherichia coli (51.27 %), Klebsiella pneumoniae (37.97%), and Enterobacter cloacae (6.96%). The most common carbapenemase genes harbored by gastrointestinal CRE strains were blaNDM-5, blaNDM-1, and blaIMP-4. Hematological malignancies, respiratory diseases, otolaryngological diseases, nervous system diseases, oral administration of third-generation cephalosporins, and the combined use of two or more antibiotics were independently associated with CRE colonization.

Effects of eyeshades in sleep quality and pain after surgery in school-age children with supracondylar humeral fractures.

Objective: This study aimed to explore the effects of eye masks on the sleep quality and pain of children over 5 years old with humeral supracondylar fracture after surgery. Methods: Fifty children with humeral supracondylar fracture who underwent closed reduction and percutaneous pinning (CRPP) in the Pediatric orthopaedic Department of a provincial hospital in China from February 2020 to December 2021 were selected. The children were randomly divided into the experimental group (n = 25) and the control group (n = 25). Children in the control group were given routine sleep care, and the children in the experimental group were given a sleep intervention with eye masks for three nights after surgery. The Pittsburgh Sleep Quality Index was used to evaluate the sleep quality of the children. The Children's Pain Behaviour Scale was used to evaluate the pain of the children. Results: After three nights of receiving the eye mask intervention, the children in the experimental group had significantly lower sleep quality scores than those in the control group; the difference was statistically significant (p < 0.05), and the children in the experimental group had higher sleep quality. The experimental group's pain scores were significantly lower than the control group's, and the difference was statistically significant (p < 0.05), and the children in the experimental group experienced less post-operative pain. Conclusions: Eye masks are a simple, safe and economical intervention, that is beneficial for improving the sleep quality and reducing pain in children over 5 years old with humeral supracondylar fracture after closed reduction and percutaneous pinning. It can be used as a reference and basis for clinical pain relief and sleep quality after surgery for supracondylar fractures of the humerus in children.

External application of mirabilite before surgery can reduce the inflammatory response and accelerate recovery in mild acute biliary pancreatitis.

OBJECTIVE: Mild acute biliary pancreatitis (MABP) is one of the most common diseases that require surgical treatment. Previous studies have focused on the timing of laparoscopic cholecystectomy (LC) for MABP. However, the impact of its inflammatory response process on the clinical outcome has been rarely reported. This study aimed to investigate the effect of preoperative external application of mirabilite on the inflammatory response and clinical efficacy in MABP. METHODS: Medical records of patients undergoing LC due to MABP from November 2017 to June 2022 were retrospectively reviewed. Prior to surgery, the control group received the same baseline treatment measures as the study group. The difference was the addition of external application of mirabilite in the study group. RESULTS: A total of 75 patients were included in the final analysis: 38 patients in the mirabilite group and 37 patients in the control group. Repeated-measures ANOVA (P < 0.01) showed that the white blood cell count (WBC) on the 3rd day of admission and the WBC and C-reactive protein (CRP) level on the 5th day of admission decreased rapidly and significantly in the mirabilite group, compared with the control group. The mirabilite group had earlier anal exhaust time. The number of patients in the mirabilite group and control group with gallbladder wall ≥ 3 mm before the operation was 16 (42.11%) vs. 24 (64.86%), p = 0.048, respectively; and the number of cases with surgical drain placement was 2 (5.26%) vs. 9 (24.32%), p = 0.020, respectively. The intraoperative modified American Fertility Society (mAFS) score of adhesions was lower in the mirabilite group (1.08 ± 0.59 points) than in the control group (1.92 ± 0.60 points), p = 0.000. The mirabilite group, compared to the control group, p = 0.000, had a short waiting time for surgery (5.68 ± 0.70 days vs. 6.54 ± 0.59 days), short operation time (38.03 ± 5.90 min vs. 48.51 ± 8.37 min), and reduced hospitalization time (8.95 ± 0.96 days vs. 9.84 ± 1.07 days). CONCLUSION: This study demonstrated that preoperative external application of mirabilite can reduce the inflammatory response, decrease the edema and peribiliary adhesions at the surgical site, and accelerate recovery in MABP.

Safety evaluation of human umbilical cord-mesenchymal stem cells in type 2 diabetes mellitus treatment: A phase 2 clinical trial.

BACKGROUND: Progressive pancreatic ß cell dysfunction is a fundamental aspect of the pathology underlying type 2 diabetes mellitus (T2DM). Recently, mesenchymal stem cell (MSC) transplantation has emerged as a new therapeutic method due to its ability to promote the regeneration of pancreatic ß cells. However, current studies have focused on its efficacy, and there are few clinical studies on its safety. AIM: To evaluate the safety of human umbilical cord (hUC)-MSC infusion in T2DM treatment. METHODS: An open-label and randomized phase 2 clinical trial was designed to evaluate the safety of hUC-MSC transplantation in T2DM in a Class A hospital. Ten patients in the placebo group received acellular saline intravenously once per week for 3 wk. Twenty-four patients in the hUC-MSC group received hUC-MSCs (1 × 106 cells/kg) intravenously once per week for 3 wk. Diabetic clinical symptoms and signs, laboratory findings, and imaging findings were evaluated weekly for the 1st mo and then at weeks 12 and 24 post-treatment. RESULTS: No serious adverse events were observed during the 24-wk follow-up. Four patients (16.7%) in the hUC-MSC group experienced transient fever, which occurred within 24 h after the second or third infusion; this did not occur in any patients in the placebo group. One patient from the hUC-MSC group experienced hypoglycemic attacks within 1 mo after transplantation. Significantly lower lymphocyte levels (weeks 2 and 3) and thrombin coagulation time (week 2) were observed in the hUC-MSC group compared to those in the placebo group (all P < 0.05). Significantly higher platelet levels (week 3), immunoglobulin levels (weeks 1, 2, 3, and 4), fibrinogen levels (weeks 2 and 3), D-dimer levels (weeks 1, 2, 3, 4, 12, and 24), and neutrophil-to-lymphocyte ratios (weeks 2 and 3) were observed in the hUC-MSC group compared to those in the placebo group (all P < 0.05). There were no significant differences between the two groups for tumor markers (alpha-fetoprotein, carcinoembryonic antigen, and carbohydrate antigen 199) or blood fat. No liver damage or other side effects were observed on chest X-ray. CONCLUSION: Our study suggested that hUC-MSC transplantation has good tolerance and high safety in the treatment of T2DM. It can improve human immunity and inhibit lymphocytes. Coagulation function should be monitored vigilantly for abnormalities.

Hepatic arterial infusion chemotherapy versus transarterial chemoembolization, potential conversion therapies for single huge hepatocellular carcinoma: a retrospective comparison study.

BACKGROUND: The treatment efficacy of transarterial chemoembolization (TACE) and hepatic arterial infusion chemotherapy (HAIC) for huge single hepatocellular carcinoma (HCC) has not been fully documented. The aim of this study was to compare TACE and HAIC for patients with solitary nodular HCCs greater than or equal to 10 cm without vascular invasion and metastasis. METHODS: From July 2015 to June 2020, a total of 147 patients with single nodular HCC greater than or equal to 10 cm without vascular invasion and metastasis receiving TACE ( n =77) or HAIC ( n =70) were retrospectively enrolled. The tumor response, overall survival (OS), and progression-free survival (PFS) were investigated and compared. The treatment outcome of two transarterial interventional therapies was explored. RESULTS: The objective response rate and PFS were higher in patients who received HAIC than in those who received TACE (44.3 vs. 10.4% and 8.9 vs. 4.2 months, respectively; P =0.001 and P =0.030), whereas the disease control rate and OS were not significantly different (92.9 vs. 84.4% and 21.3 vs. 26.6 months, respectively; P =0.798 and P =0.749). The decreased levels of alpha-fetoprotein and protein induced by vitamin K absence or antagonist-II (PIVKA-II) in patients treated with HAIC were significantly higher than those treated with TACE ( P =0.038 and P <0.001). Multivariable analysis showed that the aspartate aminotransferase/platelet ratio index was associated with OS, whereas albumin-bilirubin grade and PIVKA-II were associated with PFS. CONCLUSIONS: HAIC has better potential than TACE to control local tumors for huge single HCC without vascular invasion and metastasis and thus may be the preferred conversion therapy for these tumors.