Clinical characteristics of 71 patients with coronavirus disease 2019. / 71例2019å† çŠ¶ç— æ¯’ç— ä¸´åºŠç‰¹å¾åˆ†æž.

OBJECTIVES: To analyze the clinical characteristics of 71 patients with coronavirus disease 2019 (COVID-19). METHODS: The general data, epidemiological data, laboratory tests, imaging examinations, and treatment of 71 patients with COVID-19 admitted to the Sixth People's Hospital of Zhengzhou from January 19, 2020 to March 3, 2020 were retrospectively analyzed. RESULTS: Of the 71 COVID-19 patients, the ages were 4-84 (41.29±15.21) years, 38 (53.5%) patients were male, 33 (46.5%) were female, and 52 (73.2%) were in 22 clusters. The main clinical manifestations were fever (78.9%), cough (64.8%), and sputum (38.0%). The fever was mainly low and moderate, with 49 patients (69.0%) at 37.3-39.0 ℃. Most of the leukocytes, neutrophils, and lymphocytes were normal, accounting for 47 (66.2%), 51 (71.8%), and 51 (71.8%) patients, respectively; a few of them were decreased, accounting for 21 (29.6%), 16 (22.5%), and 20 (28.2%) patients, respectively. There were 38 (53.5%) and 31 (43.7%) patients with the decreased CD4+ and CD8+ T cell counts, respectively. There were 41 (57.7%), 38 (53.5%), 32 (45.1%), 26(36.6%), 22 (31.0%), 20 (28.2%), 14 (19.7%), 14 (19.7%), and 9 (12.7%) patients with the increased levels of C-reactive protein, erythrocyte sedimentation rate, procalcitonin, fibrinogen,interleukin 6, lactate dehydrogenase,D-dimer,alanine aminotransferase, and aspartate aminotransferase, respectively. Of the 71 patients, the lung was involved in 60 (84.5%) patients, the double lung was involved in 47 (66.2%) patients, and the single lung was involved in 13 (18.3%) patients. The course of the disease was long, and the time from symptom onset to the second severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) nucleic acid negative transformation was (17.22±6.34) days.There were no significant differences in the incubation period (t=-0.453, P>0.05), the complicates (χ2=0.042, P>0.05), and the time from symptom onset to diagnosis (t=-1.330, P>0.05) in patients between the non-severe group and the severe group. The onset age, gender, SARS-CoV-2 nucleic acid negative time, lymphocyte count, D-dimer, C-reactive protein, total bilirubin, direct bilirubin, lactate dehydrogenase, calcium ion, CD4+ T cell count, CD8+ T cell count, calcitonin, procalcitonin, and troponin were significantly different between the severe group and the non-severe group (all P<0.05). Among the 71 patients, 4 (5.6%) patients were mild, 59 (83.1%) were normal, and 8 (11.3%) were severe or critical. CONCLUSIONS: The aggregation phenomenon of COVID-19 is obvious. Fever and cough are the main clinical manifestations. White blood cells, neutrophils, and lymphocytes in the most patients in the early onset are normal. Most COVID-19 patients are light and ordinary type, with good prognosis.

Inhibition of IL-6/STAT3 signaling in human cancer cells using Evista.

Persistent activation of IL-6/STAT3 signaling pathway has been frequently detected in human cancer including breast cancer, colon cancer and multiple myeloma. IL-6/STAT3 can be a promising target for cancer prevent and treatment. However, few STAT3 inhibitors with high efficiency, specificity and safety is available for present clinical cancer therapy. Evista (Raloxifene·HCl) is known as selective estrogen receptor modulator which has been used for the prevention and treatment of osteoporosis and was approved for reducing the risk of invasive breast cancer. Our previous study found that Raloxifene inhibited IL-6/GP130 interaction, resulting in blockade of STAT3 phosphorylation. In our present study, we examined the effect on IL-6/GP130/STAT3 signaling pathway and cancer cell viability with Evista. We first demonstrated Evista inhibited constitutive activation of STAT3 in breast cancer cell line MDB-MB-231, colon cancer cell line HCT116 and multiple myeloma cancer cell line U266. Evista also inhibited phosphorylation of STAT3 induced by IL-6 in MCF-7, HT29 and MM.1S cancer cell lines. Induction of apoptosis was exerted in MDA-MB-231, HCT116 and U266 as evidenced by increased caspase-3 cleavage. However, Evista did not inhibit STAT1, STAT2, STAT4 or STAT6 phosphorylation elicited by IFN-α, IFN-γ and IL-4, nor phosphorylation of STAT3 induced by LIF in MCF-7 cell lines. Evista attenuated STAT3 phosphorylation, decreased STAT3 transcriptional activity but much less in pGL3 and AP1 transcriptional luciferase activity, and decreased cell viability in vitro. These results suggest that it may be possible for Evista to emerge as a chemoprevention agent for breast cancer and other cancers such as colon cancer or multiple myeoloma by targeting IL-6/STAT3 signaling.

Recent advances in drug delivery systems based on natural and synthetic polymes for treating obesity.

Obesity stands as a pervasive global public health issue, posing a formidable threat to human well-being as its prevalence continues to surge year by year. Presently, pharmacological treatment remains the favored adjunct strategy for addressing obesity. However, conventional delivery methods suffer from low bioavailability and the potential for side effects, underscoring the pressing need for more efficient and targeted delivery approaches. Recent research has delved extensively into emerging drug delivery systems employing polymers as carriers, with numerous preclinical studies contributing to the growing body of knowledge. This review concentrates on the utilization of natural polymers as drug delivery systems for the treatment of obesity, encompassing recent advancements in both natural and synthetic polymers. The comprehensive exploration includes an analysis of the advantages and disadvantages associated with these polymer carriers. The examination of these characteristics provides valuable insights into potential future developments in the field of drug delivery for obesity treatment.

Biodegradable polyester-based nano drug delivery system in cancer chemotherapy: a review of recent progress (2021-2023).

Cancer presents a formidable threat to human health, with the majority of cases currently lacking a complete cure. Frequently, chemotherapy drugs are required to impede its progression. However, these drugs frequently suffer from drawbacks such as poor selectivity, limited water solubility, low bioavailability, and a propensity for causing organ toxicity. Consequently, a concerted effort has been made to seek improved drug delivery systems. Nano-drug delivery systems based on biodegradable polyesters have emerged as a subject of widespread interest in this pursuit. Extensive research has demonstrated their potential for offering high bioavailability, effective encapsulation, controlled release, and minimal toxicity. Notably, poly (ε-caprolactone) (PCL), poly (lactic-co-glycolic acid) (PLGA), and polylactic acid (PLA) have gained prominence as the most widely utilized options as carriers of the nano drug delivery system. This paper comprehensively reviews recent research on these materials as nano-carriers for delivering chemotherapeutic drugs, summarizing their latest advancements, acknowledging their limitations, and forecasting future research directions.

Functionalized TMC and ε-CL elastomers with shape memory and self-healing properties.

Introduction: Smart elastomers, which possess self-healing and shape memory capabilities, have immense potential in the field of biomedical applications. Polycarbonates and polyesters have gained widespread interest due to their remarkable biocompatibility over the last century. Nevertheless, the lack of functional versatility in conventional polyesters and polycarbonates means that they fall short of meeting the ever-evolving demands of the future. Methods: This paper introduced a new smart elastomer, named mPEG43-b-(PMBC-co-PCL)n, developed from polyester and polycarbonate blends, that possessed shape memory and self-heal capabilities via a physical crosslinking system. Results: The material demonstrated a significant tensile strength of 0.38 MPa and a tensile ratio of 1155.6%, highlighting its favorable mechanical properties. In addition, a conspicuous shape retrieval rate of 93% was showcased within 32.5 seconds at 37°C. Remarkably, the affected area could be repaired proficiently with no irritation experienced during 6h at room temperature, which was indicative of an admirable repair percentage of 87.6%. Furthermore, these features could be precisely modified by altering the proportion of MBC and ε-CL to suit individual constraints. Discussion: This innovative elastomer with exceptional shape memory and self-heal capabilities provides a solid basis and promising potential for the development of self-contracting intelligent surgical sutures in the biomedical field.

Mid-term prognosis of the stromal vascular fraction for knee osteoarthritis: a minimum 5-year follow-up study.

BACKGROUND: The short-term safety and efficacy of stromal vascular fraction (SVF) in treating knee osteoarthritis (KOA) have been extensively studied but the mid-term and long-term prognoses remain unknown. METHODS: 126 KOA patients were recruited and randomly assigned to SVF group and hyaluronic acid (HA) group (control group). The scores of visual analogue scale (VAS) and the Western Ontario and McMaster University Osteoarthritis Index (WOMAC) were assessed and compared between the two groups 1, 2, 3, and 5 years after treatment. The endpoint was defined as surgeries related to KOA or clinical scores exceeding the patient acceptable symptom state (PASS). RESULTS: The VAS and WOMAC scores in the SVF group were significantly better than those in the HA group during the 5-year follow-up after treatment. The average responsive time to SVF treatment (61.52 months) was significantly longer than HA treatment (30.37 months). The adjusted Cox proportional hazards model showed that bone marrow lesion (BML) severity, body mass index (BMI) and treatment were independent risk factors and that the use of SVF reduced the risk of clinical failure by 2.602 times. The cartilage volume was reduced in both the SVF and control groups at 5 years but reduced less in the SVF group. CONCLUSIONS: Up to 5 years after SVF treatment, acceptable clinical state was present for approximately 60% of patients. BML severity and BMI were independent predictors of the prognosis. TRIAL REGISTRY: This study was retrospectively registered at Chinses Clinical Trial Registry with identifier ChiCTR2100052818 and was approved by ethics committee of the First Affiliated Hospital of Zhejiang Chinese Medical University, number 2013-X-063.

Cellulose microfibrils grafted with PBA via surface-initiated atom transfer radical polymerization for biocomposite reinforcement.

Immobilizing poly(butyl acrylate) (PBA) on cellulose microfibrils (CMFs) by atom transfer radical polymerization (ATRP) of butyl acrylate (BA) on the surface of 2-bromoisobutyryl-functionalized CMF generated highly hydrophobic microfibrils (CMF-PBA) with a hard core and a soft-shell structure. TGA and static water contact angle results suggested that the surfaces of the modified CMF samples were not completely covered by PBA chains until the molecular weight of grafts became sufficiently long. The GPC results indicated that the grafts with low molecular weight showed controlled/"living" characteristics of the surface-initiated ATRP; however, there existed more side reactions with the increase in molecular weights. Biocomposites consisting of polypropylene (PP) and CMF-PBA samples exhibited significantly improved compatibility, interface adhesion, and mechanical properties with the increase in PBA graft length. The findings confirmed that the longer grafts facilitated the better entanglement of PBA grafts with PP macromolecules and thus further improved the mechanical properties.

The Metarhizium anisopliae Toxin, Destruxin A, Interacts with the SEC23A and TEME214 Proteins of Bombyx mori.

Destruxin A (DA), a mycotoxin isolated from the entomopathogenic fungus Metarhizium anisopliae, has good insecticidal and immune-inhibitory activity, but the action mechanism has not yet been elucidated. In order to identify the DA-binding proteins, we conducted drug affinity responsive target stability (DARTS) experiments, which indicated that the silkworm's (Bombyx mori) transmembrane protein 214 (BmTEME214) and protein transport protein SEC23A isoform X2 (BmSEC23) are the potential DA-binding proteins. The current research was focused on validation of the interaction between DA and these two proteins via bio-layer interferometry (BLI) in vitro, insect two-hybrid (I2H) in Sf9 cells, and RNAi in the insect. The results of the BLI tests showed that DA has strong affinity to bind BmTEME214 and BmSEC23 proteins with a KD value of 0.286 and 0.291 µM, respectively. In the I2H experiments, DA inhibited (at 0.02 µg/mL) and activated (at 0.002-0.0002 µg/mL) the protein interactions of BmSEC23-BmSEC13, but it only inhibited the BmTMEM214-BmSEC13L interaction. Furthermore, in the RNAi tests, an apparent increase in the silkworm's mortality was recorded in the joint treatment of DA with dsBmSEC23 or dsBmTMEM214 when compared with the single treatment of DA (1.5 µg/g body), 40 µg/g body dsBmSEC23, or dsBmTMEM214. This research confirmed that BmSEC23 and BmTMEM214 are the DA-binding proteins and provided new insights to understand the action mechanism of DA.

Concealed mesenteric ischemia after total knee arthroplasty: A case report.

BACKGROUND: In critical care medicine, mesenteric ischemia (MI) is a life-threatening disease that can be present in both critically ill patients and those undergoing major surgery. For the first time, we report a case of concealed MI with a long course after knee arthroplasty. CASE SUMMARY: A male patient underwent left total knee arthroplasty for gouty arthritis and developed a persistent fever and persistently high levels of serum infection markers after surgery. He was considered to have a periprosthetic site infection and treated with antibiotics and colchicine, periprosthetic debridement was performed, and the spacer was replaced, but no improvement was seen. At 54 d after arthroplasty, the patient developed gastrointestinal symptoms of nausea and vomiting, abdominal distention, and subsequently, cloudiness of consciousness, and hypotensive shock. Finally, the patient was diagnosed with ascending colonic mesentery ischemia with necrosis after laparotomy, which improved after right hemicolectomy. CONCLUSION: Concealed MI without gastrointestinal symptoms after major surgery is rare and easily misdiagnosed. Orthopedic surgeons need to be aware of this complication.

Subchondral bone as a novel target for regenerative therapy of osteochondritis dissecans: A case report.

BACKGROUND: Osteochondritis dissecans (OCD) is a rare disease of unclear cause characterized by subchondral bone damage and overlying cartilage defects. The current report presents the results of subchondral bone as a novel target for implantation of peripheral blood stem cells (PBSCs) in the treatment of OCD. CASE SUMMARY: A 16-year-old patient diagnosed with OCD underwent subchondral bone implantation of PBSCs. Four months later, the patient's visual analog scale scores, Western Ontario and McMaster University osteoarthritis index, and whole-organ magnetic resonance imaging score improved significantly, and regeneration of cartilage and subchondral bone was observed on magnetic resonance imaging. CONCLUSION: This is the first case of OCD treated with subchondral bone as an implantation target of PBSCs, which highlights the importance of subchondral bone for cartilage repair. This treatment could be a potential option for articular cartilage and subchondral bone recovery in OCD.

Destruxin A Induces and Binds HSPs in Bombyx mori Bm12 Cells.

Destruxin A (DA) is a cyclodepsipeptidic mycotoxin isolated from the entomopathogenic fungus, Metarhizium anisopliae. It has insecticidal activity against host insect's innate immunity system, but the molecular mechanism is not yet elucidated. In our previous experiment, four HSPs (heat shock proteins, BmHSP70-3, BmHSP75, BmHSP83, and BmHSCP) were characterized from the specific protein electrophoretic bands of Bombyx mori Bm12 cell line treated with DA in the test of drug affinity responsive target stability (DARTS), which implied that these HSPs might be kinds of DA-affinity proteins, or DA induces them up-regulated expression. Therefore, in current research, the interactions of DA and HSPs were explored through analysis of bio-layer interferometry (BLI) employing FortBio OcteteQK. The expression levels of HSPs genes were surveyed by quantitative real-time polymerase chain reaction (qPCR). The results indicated that DA had no interactions with BmHSP70-3, BmHSP75, and BmHSP83, but had affinity to BmHSCP with a KD value of 88.1 µM, in BLI analysis. However, the expression levels of all HSPs genes were significantly up-regulated after the Bm12 cells were treated by DA. In conclusion, DA can induce the four HSPs expression in Bm12 cells, but DA only binds to BmHSCP. Our research provides new insights on understanding of the action mechanisms of destruxins.

Synthesis and characterization of a novel water-soluble cationic diblock copolymer with star conformation by ATRP.

A water-soluble cationic diblock copolymer, CD-PAM-b-PMeDMA, was synthesized through atom transfer radical polymerization (ATRP) from a ß-cyclodextrin (CD) macroinitiator with 10-active sites (10Br-ß-CD). In order to reduce the cytotoxicity of the CD-PAM-b-PMeDMA, biocompatible polyacrylamide (PAM) was first introduced onto the surface of ß-CD as a scaffold structure by ATRP using the 10Br-ß-CD as a macroinitiator. The reaction conditions of AM were explored and optimized. The ATRP of [2-(methacryloyloxy)ethyl] trimethyl ammonium chloride (MeDMA) was also performed to synthesize the second cationic block using the resulting CD-PAM as a macroinitiator. The resulting diblock copolymer shows an increased hydrodynamic radius in aqueous solution with a pretty low concentration compared with ß-CD. In addition, it appears a near-uniform coniform after being deposited on mica ascribed to the presence of an asymmetric 10-arm structure.