[This corrects the article DOI: 10.1016/j.apsb.2021.08.008.].

Objective To investigate the genetic characteristics of the VP1 region of Coxsackievirus A10 (CVA10) in Yunnan Province. Methods Fecal samples of suspected hand, foot and mouth disease (HFMD) were subjected to real-time fluorescent quantitative PCR for detection of enterovirus CVA10. Positive samples were subjected to VP1 gene sequence amplification and Sanger sequencing. Sequence splicing was performed with DNAstar7.1 Seqman software, and nucleotide sequence and amino acid site analysis were performed using Mega 6.0 software. Results The sequencing of VP1 gene of CVA10 obtained a sequence of 894 nucleotides, encoding 298 amino acids. Compared with the original strain, there were mainly three active amino acid mutation regions, 13-33, 141-142, and 283-285. The nucleotide difference rate between the Yunnan isolates and the reference strain ranged from 16.92% to 30.90%, and the amino acid difference rate ranged from 2.58% to 4.00%. C1 and C2 group nucleotide difference was 10.58%, and the amino acid difference rate was 1.80%. The VP1 150-176 region exhibited highly conserved characteristics. Six CVA10 strains and Sichuan strain MW178898 belonged to the C1 group of the C genotype. The other 14 CVA10 strains belonged to the C2 group. Conclusion VP1 gene mutation is active and CVA10 is an important pathogen of HFMD in Yunnan. C2 genotype of CVA10 is dominant in this study, and C1 and C2 have co-circulated in Yunnan. It is necessary to strengthen monitoring and develop multivalent vaccines containing CVA10 epidemic genotype.

Microwave thermochemotherapy (MTC) has been applied to treat lip squamous cell carcinoma (LSCC), but a deeper understanding of its therapeutic mechanisms and molecular biology is needed. To address this, we used single-cell transcriptomics (scRNA-seq) and spatial transcriptomics (ST) to highlight the pivotal role of tumor-associated neutrophils (TANs) among tumor-infiltrating immune cells and their therapeutic response to MTC. MNDA⁺ TANs with anti-tumor activity (N1-phenotype) are found to be abundantly infiltrated by MTC with benefit of increased blood perfusion, and these TANs are characterized by enhanced cytotoxicity, ameliorated hypoxia, and upregulated IL1B, activating T&NK cells and fibroblasts via IL1B-IL1R. In this highly anti-tumor immunogenic and hypoxia-reversed microenvironment under MTC, fibroblasts accumulated in the tumor front (TF) can recruit N1-TANs via CXCL2-CXCR2 and clear N2-TANs (pro-tumor phenotype) via CXCL12-CXCR4, which results in the aggregation of N1-TANs and extracellular matrix (ECM) deposition. In addition, we construct an N1-TANs marker, MX2, which positively correlates with better prognosis in LSCC patients, and employ deep learning techniques to predict expression of MX2 from hematoxylin-eosin (H&E)-stained images so as to conveniently guide decision making in clinical practice. Collectively, our findings demonstrate that the N1-TANs/fibroblasts defense wall formed in response to MTC effectively combat LSCC.
Humans ; Neutrophils/metabolism* ; Single-Cell Analysis ; Lip Neoplasms/genetics* ; Hyperthermia, Induced/methods* ; Microwaves/therapeutic use* ; Transcriptome ; Carcinoma, Squamous Cell/immunology* ; Tumor Microenvironment

Objective:To explore the impact of home enteral nutrition (HEN) on the treatment strategy of patients with high position intestinal fistula.Methods:The clinical and follow-up data of 36 patients with high position intestinal fistula requiring HEN treated in Beijing Tsinghua Changgung Hospital from Jan 2021 to Sep 2023 was retrospectively analyzed.Results:Among the 36 cases, 2 had indwelling nasogastric tubes, 12 had indwelling nasojejunal nutritional tubes, and 22 had percutaneous jejunostomy. The incidence of HEN-related complications in patients was 13.9%, and there were no serious catheter complications.During HEN, high position intestinal fistula healed in 19 cases (52.8%), returned to the hospital for the next stage of intestinal fistula treatment in 11 cases (30.6%), needed to return to the hospital for nutritional support in 1 case (2.8%), and intestinal fistula aggravated to terminate HEN in 2 cases (5.6%).Conclusion:Under the management of professional team, HEN via nasogastric/jejunal nutritional tube or percutaneous jejunostomy is safe and feasible in patients with high intestinal fistula.

Substantial progress in the use of chemo-photodynamic nano-drug delivery systems (nano-DDS) for the treatment of the malignant breast cancer has been achieved. The inability to customize precise nanostructures, however, has limited the therapeutic efficacy of the prepared nano-DDS to date. Here, we report a structurally defined tandem-responsive chemo-photosensitive co-nanoassembly to eliminate primary breast tumor and prevent lung metastasis. This both-in-one co-nanoassembly is prepared by assembling a biocompatible photosensitive derivative (pheophorbide-diphenylalanine peptide, PPA-DA) with a hypoxia-activated camptothecin (CPT) prodrug [(4-nitrophenyl) formate camptothecin, N-CPT]. According to computational simulations, the co-assembly nanostructure is not the classical core-shell type, but consists of many small microphase regions. Upon exposure to a 660 nm laser, PPA-DA induce high levels of ROS production to effectively achieve the apoptosis of normoxic cancer cells. Subsequently, the hypoxia-activated N-CPT and CPT spatially penetrate deep into the hypoxic region of the tumor and suppress hypoxia-induced tumor metastasis. Benefiting from the rational design of the chemo-photodynamic both-in-one nano-DDS, these nanomedicines exhibit a promising potential in the inhibition of difficult-to-treat breast tumor metastasis in patients with breast cancer.

Background: and Purpose Patients presenting with clinical characteristics that are strongly suggestive of neuromyelitis optica spectrum disorders (NMOSD) have a high risk of developing definite NMOSD in the future. Little is known about the clinical course, treatment, and prognosis of these patients with likely NMOSD at disease onset. Methods: This study prospectively recruited and visited 24 patients with the limited form of NMOSD (LF-NMOSD) at disease onset from November 2012 to June 2021. Their demographics, clinical course, longitudinal aquaporin-4 immunoglobulin G (AQP4-IgG) serology, MRI, therapeutic management, and outcome data were collected and analyzed. Results: The onset age of the cohort was 38.1±12.0 years (mean±standard deviation). The median disease duration was 73.5 months (interquartile range=44.3–117.0 months), and the follow-up period was 54.2±23.8 months. At the end of the last visit, the final diagnosis was categorized into AQP4-IgG-seronegative NMOSD (n=16, 66.7%), AQP4-IgG-seropositive NMOSD (n=7, 29.2%), or multiple sclerosis (n=1, 4.2%). Seven of the 24 patients (29.2%) experienced conversion to AQP4-IgG seropositivity, and the interval from onset to this serological conversion was 37.9±21.9 months. Isolated/mixed area postrema syndrome (APS) was the predominant onset phenotype (37.5%). The patients with isolated/mixed APS onset showed a predilection for conversion to AQP4-IgG seropositivity. All patients experienced a multiphasic disease course, with immunosuppressive therapy reducing the incidence rates of clinical relapse and residual functional disability. Conclusions Definite NMOSD may be preceded by LF-NMOSD, particularly isolated/ mixed APS. Intensive long-term follow-up and attack-prevention immunotherapeutic management is recommended in patients with LF-NMOSD.

Pure drug-assembled nanomedicines (PDANs) are currently under intensive investigation as promising nanoplatforms for cancer therapy. However, poor colloidal stability and less tumor-homing ability remain critical unresolved problems that impede their clinical translation. Herein, we report a core-matched nanoassembly of pyropheophorbide a (PPa) for photodynamic therapy (PDT). Pure PPa molecules are found to self-assemble into nanoparticles (NPs), and an amphiphilic PEG polymer (PPa-PEG

Tumor metastasis is responsible for chemotherapeutic failure and cancer-related death. Moreover, circulating tumor cell (CTC) clusters play a pivotal role in tumor metastasis. Herein, we develop cancer-specific calcium nanoregulators to suppress the generation and circulation of CTC clusters by cancer membrane-coated digoxin (DIG) and doxorubicin (DOX) co-encapsulated PLGA nanoparticles (CPDDs). CPDDs could precisely target the homologous primary tumor cells and CTC clusters in blood and lymphatic circulation. Intriguingly, CPDDs induce the accumulation of intracellular Ca

Objective: To investigate the feasibility of echocardiography-guided closed-chest repeated intraventricular blood sampling in mice, and to clarify the maximum blood volume that can be collected by this method, and whether the method can be used for long-term repeated blood collection in mice. Methods: Twenty-four male C57BL/6J mice (10-14 weeks old) were divided into the terminal experiment group (n=4, for investigating the maximum blood amount that could be sampled at one time), the repeated 0.5 ml blood collection group (n=10, sampling 0.5 ml whole blood each time, once every two days for consecutive 4 weeks), and the repeated 0.75 ml blood collection group (n=10, sampling 0.75 ml whole blood each time, once every two days for consecutive 4 weeks). High-frequency echocardiography was used to display the largest section of the left ventricle, guiding the insulin syringe needle through the thorax into the left ventricle for blood collection. In the repeated 0.5 ml blood collection group, echocardiography was used to detect the cardiac structure and function before blood collection, three minutes after blood collection, and one week after the last (the 14th) blood collection. Results: We successfully performed echocardiography-guided closed-chest intraventricular blood sampling, with an average operating time (88±19)s per mouse, and a maximum blood volume (1.43±0.11)ml per mouse. In the repeated 0.5 ml blood collection group, heart rate, left ventricular ejection fraction, left ventricular fractional shortening, left ventricular end-diastolic dimension and left ventricular posterior wall end-diastolic thickness remained uncganged before the first blood collection and after 4 weeks of repeated blood collection (all P>0.05). No death in the repeated 0.5 ml blood collection group. However, in the 0.75 ml blood collection group, two mice died before the end point. Conclusions The echocardiography-guided closed-chest intraventricular blood sampling is a safe, minimally invasive, convenient and efficient method, and can be used repeatedly for long-term blood collection in mice.

Objective To observe the effects of Soyasaponins on inflammatory factors, antioxidant activity and exercise ability in rats with severe heat stroke. Methods Eighty male Sprague-Dawley (SD) rats were randomly divided into normal control group, heat shock model group, saline control group and Soyasaponin group, The rats that died during the experiment or with a low rectal temperature (< 41℃) were excluded, and finally 54 rats were included, 18 rats remaining in each group. The rats in the heat shock model group were placed in the simulated hot climate animal cabin at 30 ℃, and the temperature within 30 minutes was raised to 39 ℃ in the cabin with 65% humidity; in the mean time, the rat models of heat shock were replicated under the following situations: let the rats exercise on a treadmill with running speed set at 15 m/min, slope degree 0°, once running for 8 minutes, interval 2 minutes and the heat shock time was 90 minutes, the rats in the normal control group were fed in an environment with temperature ranging from 23-25 ℃ and relative humidity ranging from 50%-70%. After the establishment of models, the saline control group and Soyasaponin group were given daily saline and Soyasaponin (10 mg/kg) respectively by gavage for 3 consecutive months, while the heat shock model group was not given any treatment. The femoral artery blood was collected 24 hours after the rats left the cabin. The serum levels of interleukins (IL-6, IL-1β), tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ), malonaldehyde (MDA), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) were measured by enzyme-linked immunosorbent (ELISA) and the contents of serum hemoglobin (Hb), serum urea (BUN), lactate dehydrogenase (LDH) and blood lactic acid (Lac) were measured by automatie biochemical analyzer. Results The levels of IL-6, IL-1β, TNF-α, IFN-γ, MDA, Hb, BUN, LDH, Lac in heat shock model group were significantly higher than those of the normal control group [IL-6 (ng/L): 86.17±4.82 vs. 12.60±3.49, IL-1β (ng/L): 83.00±5.98 vs. 15.70±3.64, TNF-α (ng/L): 72.22±6.93 vs. 13.75±2.69, IFN-γ (ng/L): 36.22±3.02 vs. 7.35±1.60, MDA (nmol/mg): 19.78±4.56 vs. 6.40±1.35, Hb (g/L): 136.22±1.93 vs. 126.75±5.84, BUN (mmol/L):21.06±3.44 vs. 5.65±1.35, LDH (μmoL·s-1·L-1): 9.65±0.83 vs. 2.12±0.17, Lac (mmol/L): 552.56±78.33 vs. 1.32±0.18, all P ＜ 0.05], SOD and GSH-Px were significantly lower than those in normal control group [SOD (kU/L):97.89±10.57 vs. 126.65±11.35, GSH-Px (kU/L): 19.22±2.58 vs. 43.45±4.02]; however, the levels of IL-6, IL-1β, TNF-α, IFN-γ, MDA, BUN, LDH and Lac in Soyasaponin group were significantly lower than those in heat shock model group [IL-6 (ng/L): 45.28±3.54 vs. 86.17±4.82, IL-1β (ng/L): 41.61±2.93 vs. 83.00±5.98, TNF-α (ng/L):37.22±2.46 vs. 72.22±6.93, IFN-γ (ng/L): 19.22±2.60 vs. 36.22±3.02, MDA (nmol/mg): 11.28±1.74 vs. 19.78±4.56, BUN (mmol/L): 11.78±2.13 vs. 21.06±3.44, LDH (μmoL·s-1·L-1): 3.70±0.26 vs. 9.65±0.83, Lac (mmol/L): 274.56±59.08 vs. 552.56±78.33, all P < 0.01], SOD, GSH-Px and Hb were significantly higher than those of heat shock model group [SOD (kU/L): 116.11±11.28 vs. 97.89±10.57, GSH-Px (kU/L): 31.17±2.90 vs. 19.22±2.58, Hb (g/L): 141.33±3.79 vs. 136.22±1.93, all P < 0.01]; there were no significant statistical differences in above indexes between heat shock model group and saline control group (all P > 0.05). Conclusion After heat shock and exercise management, the production and release of inflammatory factors are increased, and the level of lipid peroxidation was elevated in rats. The Soyasaponin can improve the ability to withstand heat shock and strong exercise by reducing the production and release of inflammatory factors and lipid peroxidation in the rats with severe heatstroke.