Necessity for higher teicoplanin doses in older adults: a multicenter prospective observational study in China.

BACKGROUND: Many older adult patients receive low-dose teicoplanin with varied regimens, leading to a lack of clarity on its optimal regimens and toxicity profiles in China. This study aimed to clarify these aspects by analyzing teicoplanin treatment concentrations and toxicities. METHODS: We included older adult patients administered teicoplanin at four tertiary hospitals in Beijing from June 2021 to July 2023, targeting a trough concentration (Cmin) ≥ 10 mg/L. Teicoplanin concentrations and toxicities were monitored dynamically. RESULTS: From 204 patients, we obtained 632 teicoplanin concentrations. Most patients (83.3%) received low-dose regimens. Suboptimal concentrations were found in 66.4% of patients within 7 days of treatment and 17.0% after 15 days. Cmin gradually increased with treatment duration and was influenced initially by creatinine and by both body weight and creatinine from days 8 to 14. The target concentration was achieved in 53.1%, 33.9%, 15.6%, and 5.5% of patients at 3, ≤ 7, 8-14, and ≥ 15 days after withdrawal, respectively. Slow elimination was associated with average Cmin and eGFR. Nephrotoxicity, hepatotoxicity, and thrombocytopenia occurred in 12.5%, 4.1%, and 31.5% of patients, respectively, without significant differences between concentrations. CONCLUSIONS: Most older adult patients were underdosed, indicating a need for dose adjustment. Given the varied risk factors for suboptimal concentrations in different treatment stages, a one-size-fits-all regimen was ineffective. We recommend an initial dose of 400 mg at 12-h intervals for the first three days, with subsequent doses from days 4 to 14 adjusted based on creatinine and body weight; after day 14, a maintenance dose of 200 mg daily is advised. TRIAL REGISTRATION: ChiCTR2100046811; 28/05/2021.

Plastination of a sperm whale.

In 2016, two adult male sperm whales beached off of Yangkou Port in Nantong City, Jiangsu Province, China. The local government planned to preserve them as specimens, one was entrusted to Dalian Hoffen Biological Co., Ltd., and thus became the first sperm whale to be preserved by plastination. The other sperm whale was preserved in Nantong by the traditional stripping method (The skin was preserved, and then the prosthesis was filled into the skin to preserve the specimens. The material of the prosthesis was polyurethane. The outline of the animal was sculpted by suturing the skin like a bag and filling it with polyurethane). Plastination of such a large marine mammal allowed us to view the mutual adaptations of its internal structure to its specific living environment and daily habits. This sperm whale is the largest specimen in the world and this is the first time a sperm whale has been preserved using the plastination method. The plastination process also provides a method for studying the anatomy of large marine mammals for humans to understand deep-sea organisms at close contact and visual level. The plastination of this sperm whale promises to be a world class resource holding tremendous scientific, educational, and artistic value.

Effect of blended learning with BOPPPS model on Chinese student outcomes and perceptions in an introduction course of health services management.

Although the teaching methods of the blended learning and BOPPPS (bridge-in, objective, preassessment, participatory learning, postassessment, and summary) model are proven to be successful and highly effective at improving the academic knowledge of the students, respectively, it is unclear whether blended learning combined with the BOPPPS model (BL-BOPPPS) could work well in an introduction course of health services management (HSM) for the health management students in China. The study investigated the perceptions and effects of implementing the BL-BOPPPS model on student learning outcomes in an introduction course of HSM. The intervention group consisted of 55 students introduced to the BL-BOPPPS model, while the control group consisted of 54 students who received a conventional lecture. After the end of course, the effectiveness of teaching was self-assessed with questionnaires by all students, and examination scores for the two groups were compared. The students' satisfaction levels of BL-BOPPPS teaching strategy were up to 81.8% in the intervention group. Compared with the control group, the intervention group showed significant elevation of perception scores of skills (P = 0.001), initiative (P = 0.002), self-control (P = 0.008), self-efficacy (P = 0.001), motivation (P = 0.004), and the academic performance (P = 0.001). The BL-BOPPPS model could stimulate the enthusiasm and interest of health students; boost students' skills, initiative, and motivation in learning; and improve the self-directed learning ability, academic performance, and teaching quality. The findings provide a basis of evidence for the promotion of the BL-BOPPPS model in various disciplines in Chinese colleges and universities.

Discovery of secondary sulphonamides as IDO1 inhibitors with potent antitumour effects in vivo.

Indoleamine 2,3-dioxygenase 1 (IDO1) as a key rate-limiting enzyme in the kynurenine pathway of tryptophan metabolism plays an important role in tumour immune escape. Herein, a variety of secondary sulphonamides were synthesised and evaluated in the HeLa cell-based IDO1/kynurenine assay, leading to the identification of new IDO1 inhibitors. Among them, compounds 5d, 5l and 8g exhibited the strongest inhibitory effect with significantly improved activity over the hit compound BS-1. The in vitro results showed that these compounds could restore the T cell proliferation and inhibit the differentiation of naïve CD4+ T cell into highly immunosuppressive FoxP3+ regulatory T (Treg) cell without affecting the viability of HeLa cells and the expression of IDO1 protein. Importantly, the pharmacodynamic assay showed that compound 5d possessed potent antitumour effect in both CT26 and B16F1 tumours bearing immunocompetent mice but not in immunodeficient mice. Functionally, subsequent experiments demonstrated that compound 5d could effectively inhibit tumour cell proliferation, induce apoptosis, up-regulate the expression of IFN-γ and granzyme B, and suppress FoxP3+ Treg cell differentiation, thereby activate the immune system. Thus, compound 5d could be a potential and efficacious agent for further evaluation.

Role of IL-1 Family Cytokines IL-36, IL-37, IL-38 in Osteoarthritis and Rheumatoid Arthritis: A Comprehensive Review.

Inflammatory cytokines, interleukin-36 (IL-36), IL-37, IL-38 belong to IL-1 family. The IL-36 subfamily obtains pro- and anti-inflammatory effects on various immune responses. Cytokine IL-37, has anti-inflammatory functions in immunity, and the recently identified IL-38 negatively associated with disease pathogenesis. To date, expression of IL-36, IL-37, IL-38 is reported dysregulated in osteoarthritis (OA) and rheumatoid arthritis (RA), and may be disease markers for arthritis-related diseases. Interestingly, expression of IL-38 was different either in OA patients or animal models, and expression of IL-36Ra in synovium was different in OA and RA patients. Moreover, functional studies have demonstrated significant role of these cytokines in OA and RA progress. These processes were related to immune cells and non-immune cells, where the cytokines IL-36, IL-37, IL-38 may regulate downstream signalings in the cells, and then involve in OA, RA development. In this review, we comprehensively discuss recent advancements in cytokines and the development of OA, RA. We hope that targeting these cytokines will become a potential treatment option for OA and RA in the future.

Role of hydrogels in osteoarthritis: A comprehensive review.

Osteoarthritis (OA) is a chronic, degenerative, and age-related disease. It is characterized by chronic inflammation, progressive articular cartilage destruction, and subchondral bone sclerosis. The current effective treatment for OA is limited. Hydrogel is a kind of unique carrier with well-known biocompatibility, softness, and high water content among various biomaterials. Hydrogels are developed for different biomedical applications, for instance, drug delivery, and tissue engineering. To date, a variety of hydrogels-based therapies have been used in OA patients or animal models. In this review, we comprehensively summarized the potential role of hydrogels in chondrocytes proliferation, apoptosis, and inflammatory component production and discussed the impact of hydrogels on OA development. The collection of this information will help better understand the present progress of hydrogels in OA.

Preparation of Au-RGO/TiO2 nanotubes and study on the photocatalytic degradation of ciprofloxacin.

Au-RGO/TiO2 nanotubes were prepared by anodic oxidation and electrochemical deposition, and their performance in the photocatalytic degradation of ciprofloxacin was investigated. The results showed that, compared with TiO2 nanotubes and RGO/TiO2 nanotubes, the Au-RGO/TiO2 nanotubes had the highest ciprofloxacin degradation rate, reaching 96.93% in 180 min of photocatalysis. In addition, the possible degradation products of ciprofloxacin were analyzed by liquid chromatography-mass spectrometry, and the mechanism of degradation of ciprofloxacin by Au-RGO/TiO2 nanotubes was analyzed.

Synthesis and Characterization of Fucoidan-Chitosan Nanoparticles Targeting P-Selectin for Effective Atherosclerosis Therapy.

Atherosclerosis is the key pathogenesis of cardiovascular diseases; oxidative stress, which is induced by the generated excess reactive oxygen species (ROS), has been a crucial mechanism underlying this pathology. Nanoparticles (NPs) represent a novel strategy for the development of potential therapies against atherosclerosis, and multifunctional NPs possessing antioxidative capacities hold promise for amelioration of vascular injury caused by ROS and for evading off-target effects; materials that are currently used for NP synthesis often serve as vehicles that do not possess intrinsic biological activities; however, they may affect the surrounding healthy environment due to decomposition of products. Herein, we used nontoxic fucoidan, a sulfated polysaccharide derived from a marine organism, to develop chitosan-fucoidan nanoparticles (CFNs). Then, by binding to P-selectin, an inflammatory adhesion exhibited molecule expression on the endothelial cells and activated platelets, blocking leukocyte recruitment and rolling on platelets and endothelium. CFNs exhibit antioxidant and anti-inflammatory properties. Nevertheless, by now, the application of CFNs for the target delivery regarding therapeutics specific to atherosclerotic plaques is not well investigated. The produced CFNs were physicochemically characterized using transmission electron microscopy (TEM), together with Fourier transform infrared spectroscopy (FTIR). Evaluations of the in vitro antioxidant as well as anti-inflammatory activities exhibited by CFNs were based on the measurement of their ROS scavenging abilities and investigating inflammatory mediator levels. The in vivo pharmacokinetics and binding efficiency of the CFNs to atherosclerotic plaques were also evaluated. The therapeutic effects indicated that CFNs effectively suppressed local oxidative stress and inflammation by targeting P-selectin in atheromatous plaques and thereby preventing the progression of atherosclerosis.

A feasible biocompatible hydrogel film embedding Periplaneta americana extract for acute wound healing.

The wound healing effects of pharmaceutic preparations of Periplaneta americana, Kangfuxin liquid, have been widely utilized in clinics. However, its wound repair efficacy is limited due to short retention capability on cutaneous wound location. Herein, Periplaneta americana extract (PAE), which showed pro-fibrogenic and pro-angiogeneic effects, was embedded into hydrogel film (PAE/Film) by solution cast method by blending polyvinyl alcohol, hydroxypropyl chitosan and carbomer at the weight ratio of 78/6/3, with glycerol as plasticizer. PAE/Film exhibited smooth, flexible, and excellent swelling ability (WVTR of 2464 ±â€¯31.5 g/m2/day), characterized by scanning electron microscopy, Fourier transform infrared spectroscopy, and differential scanning calorimetry, meting the condition of ideal wound dressing. The superior wound healing capacity of PAE/Film was demonstrated that it significantly accelerated wound healing process in vivo in both full-thickness skin defect and scald wounded models. Compared to saline, blank vehicle (drug-free) and free PAE group, PAE/Film could accelerate wound healed, promote re-epithelialization and collagen deposition by means of TGF-ß/Smad signal pathway activation. Taken together, this novel hydrogel film-loading PAE would be a useful pharmaceutic candidate for acute cutaneous wound health care.

Periplaneta americana Ameliorates Dextran Sulfate Sodium-Induced Ulcerative Colitis in Rats by Keap1/Nrf-2 Activation, Intestinal Barrier Function, and Gut Microbiota Regulation.

Periplaneta americana, a magic medicinal insect being present for over 300 million years, exhibits desirable therapeutic outcome for gastrointestinal ulcer treatment. Nowadays, P. americana ethanol extract (PAE) has been shown to ameliorate ulcerative colitis (UC) by either single-use or in combination with other therapeutic agents in clinics. However, its underlying mechanisms are still seldom known. Herein, we investigated the anti-UC activity of PAE by alleviating intestinal inflammation and regulating the disturbed gut microbiota structure in dextran sulfate sodium (DSS)-induced UC rats. Based on multiple constitute analyses by HPLC for quality control, PAE was administrated to DSS-induced UC rats by oral gavage for 2 weeks. The anti-UC effect of PAE was evaluated by inflammatory cytokine production, immunohistochemical staining, and gut microbiota analysis via 16S rRNA sequencing. As a result, PAE remarkably attenuated DSS-induced UC in rats. The colonic inflammatory responses manifested as decreased colonic atrophy, intestinal histopathology scores and inflammatory cytokines. In addition, PAE improved the intestinal barrier function via activating Keap1/Nrf-2 pathway and promoting the expressions of tight junction proteins. It was observed that the UC rats showed symptoms of gut microbial disturbance, i.e., the increased Firmicutes/Bacteroidetes ratio and the significantly decreased probiotics such as Lactobacillus, Roseburia, and Pectobacterium, which were negatively correlated with these detected pro-inflammatory cytokines (secreted by immune CD4+ T cells, and including IFN-γ, TNF-α, IL-6, IL-8, IL-17, IL-1ß). Besides, PAE administration regulated the abnormal intestinal microbial composition and made it similar to that in normal rats. Therefore, PAE could attenuate the DSS-induced UC in rats, by means of ameliorating intestinal inflammation, improving intestinal barrier function, and regulating the disturbed gut microbiota, especially improving beneficial intestinal flora growth, modulating the flora structure, and restoring the intestinal-immune system.

Erratum: pri-miR-34b/c rs4938723 polymorphism is associated with hepatocellular carcinoma risk: a case-control study in a Chinese population.

[This corrects the article on p. 1 in vol. 8, PMID: 28337312.].

pri-miR-34b/c rs4938723 polymorphism is associated with hepatocellular carcinoma risk: a case-control study in a Chinese population.

Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide. miR-34 induces changes of its downstream genes, and plays a key role in altering the apoptotic cycle and pathways of downstream cells, and finally influences the development of cancer. We assessed the relationship of the pri-miR-34b/c rs4938723 polymorphism with hepatocellular carcinoma risk in a Chinese population. During the period of January 2014 and December 2015, a total of 164 HCC patients and 305 healthy controls were recruited from the Inner Mongolia People's Hospital. Genotyping of the pri-miR-34b/c rs4938723 was determined using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Using χ2 test, we observed that HCC patients were likely to have a habit of alcohol consumption (χ2 = 10.24, P = 0.001) and infect with HBV or HCV (χ2 = 128.17, P < 0.001). In co-dominant model, the CC genotype of pri-miR-34b/c rs4938723 had a significant higher risk of HCC as compared with the TT genotype, and the corresponding adjusted OR (95% CI) was 4.14 (1.91-9.75). In dominant model, we observed that the TC+CC genotype were associated with an increased risk of HCC in comparison to the TT genotype (OR = 1.67, 95% CI = 1.17-2.55). In recessive model, the CC genotype was correlated with an elevated risk of HCC when compared with the TT+TC genotype (OR = 3.46, 95% CI = 1.62-8.54). The pri-miR-34b/c rs4938723 polymorphism was associated with a higher risk of HCC in the Chinese population examined. Further large-scale and multi-center studies are required to confirm these results.