Overlapping infection of Nocardia farcinica and Aspergillus fumigatus in a child with X-linked chronic granulomatous disease: a case report.

BACKGROUND: Chronic granulomatous disease (CGD) is a rare inherited primary immunodeficiency syndrome, manifested as recurrent infections and inflammatory complications. Although prophylactic treatment with antibiotics and antifungals improved the outcome of CGD patients, infections remain the major cause of mortality. CASE PRESENTATION: A boy aged 3 years and 8 months was admitted to hospital complaining of lip swelling with fever for half a month and neck abscess for 11 days. After a thorough examination, severe pneumonia, respiratory failure, oral and maxillofacial space infection, and perianal abscess were confirmed. However, his condition didn't improve after initial comprehensive therapy. Subsequently, overlapping infections of Nocardia farcinica and Aspergillus fumigatus were identified by metagenomic next-generation sequencing. He was treated with imipenem, linezolid, and voriconazole intravenously, plus taking oral compound sulfamethoxazole. Later, his condition improved. Through whole-exome sequencing, the child was ultimately diagnosed as X-linked chronic granulomatous disease (X-CGD) caused by CYBB gene mutation. Allogeneic hematopoietic stem cell transplantation was the potential sanative approach but there were no available human leukocyte antigen compatible donors for the child. The family requested to transfer to a superior hospital for further treatment. Two months later, we followed up the child's family. Unfortunately, the child had expired due to severe infection. CONCLUSION: To our knowledge, this is the first case of overlapping infection of Nocardia farcinica and Aspergillus fumigatus identified by metagenomic next-generation sequencing in a child with X-CGD from China. For infectious pathogens that are hard to diagnosis by traditional detection methods, metagenomic next-generation sequencing is recommended as an adminicle or indispensable approach for microbial identification. Patients with X-CGD have poor prognosis, early diagnosis and intervention of X-CGD may reduce the mortality.

Intranasal temperature-sensitive hydrogels of cannabidiol inclusion complex for the treatment of post-traumatic stress disorder.

Post-traumatic stress disorder (PTSD) is a psychiatric disease that seriously affects brain function. Currently, selective serotonin reuptake inhibitors (SSRIs) are used to treat PTSD clinically but have decreased efficiency and increased side effects. In this study, nasal cannabidiol inclusion complex temperature-sensitive hydrogels (CBD TSGs) were prepared and evaluated to treat PTSD. Mice model of PTSD was established with conditional fear box. CBD TSGs could significantly improve the spontaneous behavior, exploratory spirit and alleviate tension in open field box, relieve anxiety and tension in elevated plus maze, and reduce the freezing time. Hematoxylin and eosin and c-FOS immunohistochemistry slides showed that the main injured brain areas in PTSD were the prefrontal cortex, amygdala, and hippocampus CA1. CBD TSGs could reduce the level of tumor necrosis factor-α caused by PTSD. Western blot analysis showed that CBD TSGs increased the expression of the 5-HT1A receptor. Intranasal administration of CBD TSGs was more efficient and had more obvious brain targeting effects than oral administration, as evidenced by the pharmacokinetics and brain tissue distribution of CBD TSGs. Overall, nasal CBD TSGs are safe and effective and have controlled release. There are a novel promising option for the clinical treatment of PTSD.

3D printing-based drug-loaded implanted prosthesis to prevent breast cancer recurrence post-conserving surgery.

Systemic chemotherapy of breast cancer is commonly delivered as a large dose and has toxic side effects. Local chemotherapy would overcome the shortcomings of systemic reconstruction and could play an important role in breast cancer surgery according to personalized demand. The application of three-dimensional (3D) printing technology makes personalized customization possible. We designed and prepared a prosthesis containing paclitaxel (PTX) and doxorubicin (DOX) microspheres (PPDM) based on 3D printing to prevent tumor recurrence and metastasis after breast conserving surgery. Polydimethysiloxane has good biocompatibility and was used as a drug carrier in this study. The average particle size of the PTX and DOX microspheres were approximately 3.1 µm and 2.2 µm, respectively. The drug loading of PTX and DOX microspheres was 4.2% and 2.1%, respectively. In vitro drug release studies demonstrated that the 3D-printed prosthesis loaded with PTX and DOX microspheres could release the drugs continuously for more than 3 weeks and thereby suppress cancer recurrence with reduced side effects. The PTX and DOX microspheres not only exerted a synergistic effect, but also achieved a good sustained release effect. In vivo evaluation showed that the PPDM could effectively inhibit breast cancer recurrence and metastasis in mice with breast cancer. PPDM are expected to achieve postoperative chemotherapy for breast cancer and be highly efficient to prevent local breast cancer recurrence and metastasis.

Topical photodynamic therapy combined with ablative "light needles" against basal cell carcinoma.

Basal cell carcinoma (BCC), a non-melanoma cancer with high morbidity in the elders, is a type of limited skin cancer with a projected appearance. Traditional treatments such as oral or injection administration are likely to result in serious side effects. Here, we developed a strategy that combined photodynamic therapy (PDT) with ablative light "needles" (carbon-dioxide laser) for the treatment of BCC, involving ß-Tetra-(4-carboxyl-phenoxy)-zinc phthalocyanine (ZnPC4) cubic phases with high drug loading, easy preparation, long local retention, good spreading ability and little toxicity. A model of nude mice with BCC was established for the study of pharmacodynamics. The light needles of low energy (53 mJ/cm2) used here could promote transdermal absorption of ZnPC4 cubic phases while those of high energy (238 mJ/cm2) alone could completely kill tumor cells with no recurrence. However, ZnPC4 cubic phases alone could not completely inhibit tumor growth, for it was distributed mainly at the topical administration site in the absence of any adjuvant technology. Therefore, the combination of photodynamics and light needles offered a good solution. Especially, the combined use of light needles with high energy and ZnPC4 cubic phases can treat BCC efficiently with no recurrence. This approach is expected to be a novel and promising medication against BCC.

ICG-loaded photodynamic chitosan/polyvinyl alcohol composite nanofibers: Anti-resistant bacterial effect and improved healing of infected wounds.

Photodynamic antimicrobial chemotherapy (PACT) has advantages of strong targeting, low resistance to drugs. Electrospinning nanofibers is favorable for wound healing. The combination of PACT and electrospinning nanofibers is appropriate for wound healing, especially infected wound. In our study, indocyanine green (ICG) as photosensitizer had obvious inhibition effects on two antibiotic-resistant bacteria, Methicillin-resistant Staphylococcus aureus (MRSA) and Meropenem-resistant Pseudomonas aeruginosa (MRPA). The optimized electrospinning solution consisted of 2% (w/v) chitosan and 7% (w/v) PVA. The nanofibers observed by scanning electron microscope showed a three-dimensional cross-network with smooth surface, the water absorption ratio of the nanofibers was up to 210%. Fourier transform infrared spectrum and X-ray diffraction showed that the intermolecular hydrogen bonding happened between chitosan and PVA in electrospinning process, which was favorable for the formation of nanofibers. ICG released rapidly from the surface of the nanofibers first and then released continuously. The photodynamic nanofibers could inhibit the bacteria and decreased the F4/80 expression of MRSA-infected rats. The improved effects of wound healing were evaluated with the morphology, wound healing radio, the increased expression of cluster of differentiation 31 (CD31), the decreased level of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6). The photosensitizer-loaded electrospinning nanofibers provide a novel promising option for treatment of infected wound.

Intranasal tetrandrine temperature-sensitive in situ hydrogels for the treatment of microwave-induced brain injury.

The brain is the most sensitive organ to microwave radiation. However, few effective drugs are available for the treatment of microwave-induced brain injury due to the poor drug permeation into the brain. Here, intranasal tetrandrine (TET) temperature-sensitive in situ hydrogels (ISGs) were prepared with poloxamers 407 and 188. Its characteristics were evaluated, including rheological properties, drug release in vitro, and mucosal irritation. The pharmacodynamics and brain-targeting effects were also studied. The highly viscous ISGs remained in the nasal cavity for a long time with the sustained release of TET and no obvious ciliary toxicity. Intranasal temperature-sensitive TET ISGs markedly improved the spatial memory and spontaneous exploratory behavior induced by microwave with the Morris water maze (MWM) and the open field test (OFT) compared to the model. The ISGs alleviated the microwave-induced brain damage and inhibited the certain mRNA expressions of calcium channels in the brain. Intranasal temperature-sensitive TET ISGs was rapidly absorbed with a shorter Tmax (4.8 h) compared to that of oral TET (8.4 h). The brain targeting index of intranasal temperature-sensitive TET ISGs was as 2.26 times as that of the oral TET. Intranasal temperature-sensitive TET ISGs are a promising brain-targeted medication for the treatment of microwave-induced brain injury.

Wound healing of laser injured skin with glycerol monooleicate cubic liquid crystal.

Laser has found increasingly wider applications in the medical filed, but laser is likely to cause damage to patients' skin. In this experiment, we were surprised to find that glyceryl monooleate (GMO)-based cubic liquid crystal had excellent healing effect on the skin of guinea pigs damaged by laser. Transepidermal water loss (TEWL), H.E. pathology, Masson trichrome dyeing, interleukin-6 (IL-6) levels and the percutaneous depth of fluorescein isothiocyanate (FITC) dyeing were used to evaluate the therapeutic effect of GMO-based cubic liquid crystals against laser damage of different degrees among guinea pigs. GMO-based cubic liquid crystals had an obvious effect in the treatment of slight and moderate laser damage. This finding may provide a effective medical treatment protocols for laser skin damage.

Nasal timosaponin BII dually sensitive in situ hydrogels for the prevention of Alzheimer's disease induced by lipopolysaccharides.

Alzheimer's disease (AD) is a common and severe brain disease with a high mortality among the elders, but no highly efficient medications are currently available. For example, timosaponin BII, an efficient anti-AD agent, has low oral bioavailability. Here, timosaponin BII was formulated in a temperature/ion-sensitive in situ hydrogel (ISG) that was well transformed into gels in the nasal environment. Timosaponin BII protected the PC12 cells injured by lipopolysaccharides (LPS) by decreasing TNF-α and IL-1ß and stabilizing F-actin. Timosaponin BII ISGs were intranasally administered to the mice every day for 38 days. On Day 36, LPS was injected to the mice to establish an AD model. Morris water maze experiments showed that the number of the animals that were able to cross the platform returned to normal and the total distance over which the animals moved in the open field also increased, which demonstrated that the spatial memory and spontaneous behavior were improved after treatment compared to the model. Moreover, an AD improver, inducible nitric oxide synthase (iNOS) in the brain, was reduced after treatment. High brain targeting effect of timosaponin BII ISGs was confirmed by in vivo fluorescence imaging. The nasal timosaponin BII dually sensitive ISGs can serve as a promising medication for local prevention of AD.