Carboxyl-functionalized dual pH/temperature-responsive poly(N-vinylcaprolactam) microgels based on isogenous comonomers for smart window applications.

Stimuli-responsive poly(N-vinylcaprolactam) (PVCL)-based microgels, which could response to small external environmental changes, have attracted great interests in the fields of biomedicine and nanotechnology. However, the preparation of such microgels meets severe challenge due to their low incorporation efficiency and thermoresponsivity passivation. To address these issues, we select 3-(tert-butoxycarbonyl)-N-vinylcaprolactam (TBVCL), a carboxyl-functionalized VCL derivative, as a comonomer to develop pH/temperature dual-responsive microgels. TBVCL, with a structure similar to VCL, enhances incorporation efficiency and colloidal stability, while reducing thermoresponsivity passivation. The volume phase transition temperature (VPTT) of the microgels can be adjusted over a broad range (19.0-49.5 °C). Notably, the radial swelling ratios of the microgels can be modulated by pH, achieving a maximum swelling ratio of 3. The distinct changes in dissolution-precipitation behavior under different temperatures or pH conditions make these microgels suitable for applications such as smart windows and sensors. Furthermore, this novel approach for fabricating microgels with pH-tunable phase-transition temperatures demonstrates significant potential for the controlled release of nanoparticles (e.g., drugs, catalysts, and quantum dots) and the development of smart nanocrystal-polymer composite sensors.

[Effect of Low-Dose Recombinant Interleukin-2 Therapy on Immunocyte Subsets in Children with Solid Tumor].

OBJECTIVE: To evaluate the effect of low-dose recombinant interleukin-2 (rIL-2) therapy on immunocyte subsets and its side effects in children with solid tumor. METHODS: A total of 22 children (11 males and 11 females) with solid tumor in our department from December 2012 to November 2017 were selected, with a median age of 9 (3-16) years old when starting IL-2 therapy. ALL surgeries and chemotherapy of children had been completed before low-dose rIL-2 therapy, and 17 cases achieved complete remission (CR) and 5 cases achieved partial remission (PR). A low-dose rIL-2 therapy was given 1 month after chemotherapy for 1 year: 4×105 IU/(m2·d), s.c. for every other day, 3 times per week. The immunocyte subsets were detected every 3 months until the end of treatment, meanwhile, disease condition and therapy-related side effects were followed up. RESULTS: After low-dose rIL-2 therapy in 22 children, the absolute values of CD3+ T cells, CD3-CD56+ natural killer cells, CD3+CD4+ helper T cells (Th) and CD3+CD8+ cytotoxic T cells were up-regulated remarkably, as well as Th/suppressor T cells (all P < 0.05). While, there were no significant differences in absolute value and proportion of CD4+CD25+CD127- Treg cells during therapy. Among the 17 children who achieved CR before rIL-2 therapy, 14 cases continued to maintain CR after therapy, while 3 cases relapsed, and with 2 died after treatment abandonment. The 5 children who achieved PR before low-dose rIL-2 therapy were evaluated CR by PET/CT scan after treatment. In the early stage of low-dose rIL-2 therapy, 1 child developed skin rashes at the injection sites, and 2 children ran a slight to mild transient fever. Their symptoms disappeared without any organ damage after symptomatic treatment. CONCLUSION: Low-dose rIL-2 therapy has good drug tolerance, and changes the distribution of anti-tumor immune-cell subgroup in peripheral blood of children with solid tumor remarkably without up-regulation of absolute value and ratio of Treg cells.

Vemurafenib combined with chemotherapy achieved sustained remission in pediatric LCH: a multi-center observational study.

BACKGROUND: Langerhans cell histiocytosis (LCH) is a myeloid neoplasia with potentially fatal consequences, and about 2/3 of cases involve the BRAFV600E kinase-activated mutation. Vemurafenib, a BRAF inhibitor, has demonstrated significant clinical improvements in LCH. However, the high relapse rate of LCH following cessation of vemurafenib therapy remains a major challenge, and alternative treatment strategies require further investigation. METHODS: In this retrospective multi-center study, we evaluated the efficacy and safety of vemurafenib combined with conventional chemotherapy in patients with severe or refractory LCH. RESULTS: Seventeen patients were enrolled in the study, with eleven classified as risk organ involvement (RO +). Six received the combination therapy as the primary treatment, and eleven after being refractory to prior chemotherapy. The overall response rate was 94.1%. Progression-free survival among all 17 patients was 70.6% (12/17) at a median follow-up of 32 months, and relapse-free survival among the 15 patients with discontinuation after a response was 73.3%(11/15) at a median follow-up of 34 months. Five of six patients (83.3%) with myeloid BRAFV600E mutations demonstrated molecular remission. The overall survival rate was 100%. Adverse events were mostly classified as grades 1 or 2. CONCLUSION: Our data suggest that the combination of vemurafenib and chemotherapy can achieve sustained clinical and molecular level relief in children with LCH, and side effects are tolerable.

Arsenic Trioxide inhibits Activation of Hedgehog Pathway in Human Neuroblastoma Cell Line SK-N-BE(2) Independent of Itraconazole.

BACKGROUND: Neuroblastoma (NB) remains associated with a low overall survival rate over the long term. Abnormal activation of the Hedgehog (HH) signaling pathway can activate the transcription of various downstream target genes that promote NB. Both arsenic trioxide (ATO) and itraconazole (ITRA) can inhibit tumor growth. OBJECTIVE: To determine whether ATO combined with ITRA can be used to treat NB with HH pathway activation, we examined the effects of ATO and ITRA monotherapy or combined inhibition of the HH pathway in NB. METHODS: Analysis of CCK8 and flow cytometry showed cell inhibition and cell cycle, respectively. Real-time PCR analysis was conducted to assess the mRNA expression of HH pathway. RESULTS: We revealed that as concentrations of ATO and ITRA increased, the killing effects of both agents on SK-N-BE(2) cells became more apparent. During G2/M, the cell cycle was largely arrested by ATO alone and combined with ITRA, and in the G0/G1 phase by ITRA alone. In the HH pathway, ATO inhibited the transcription of the SHH, PTCH1, SMO and GLI2 genes, however, ITRA did not. Instead of showing synergistic effects in a combined mode, ITRA decreased ATO inhibitory effects. CONCLUSION: We showed that ATO is an important inhibitor of HH pathway but ITRA can weaken the inhibitory effect of ATO. This study provides an experimental evidence for the clinical use of ATO and ITRA in the treatment of NB with HH pathway activation in cytology.

[Clinical Analysis of Pediatric Acute Leukemia Complicated with Septic Shock].

OBJECTIVE: To analyze the clinical characteristics of predictors in pediatric acute leukemia complicated with septic shock and explore the prognostic factors. METHODS: The clinical characteristics of 70 children with acute leukemia and complicated with septic shock hospitalized in Sun Yat-sen Memorial Hospital from March 2012 to March 2021 were retrospectively analyzed. The clinical characteristics of patients in survival group and death group were analyzed and compared. Multiple logistic regression was used to test for predictors of death. RESULTS: Among the 70 children, 41 were males and 29 were females, with a median age of 7.0 (1.0-15.0) years old. 81.4% were hospital acquired infections. The pathogens were mostly Gram-negative bacteria (50/66, 75.8%) and the clinical manifestations were cold shock. Mortality rate was 34.3% (24/70). The length of hospitalization, duration of fever and antibiotic exposure longevity before the onset of septic shock were significantly different between survival group and death group. At septic shock onset, compared with the survival group, patients in the death group were younger, had lower platelet counts and higher levels of C-reactive protein and procalcitonin, and were more likely to have acute heart failure and more mechanical ventilation (all p<0.05). The results of multivariable analysis showed that mortality was independently associated with pediatric sequential organ failure assessment score (pSOFA) (odds ratio: 1.616, 95% CI: 1.160-2.251, p=0.005) and acute heart failure (odds ratio: 18.308, 95% CI: 1.939-172.911, p=0.011). In addition, the ROC curve analysis showed that pSOFA score had AUC of 0.8551 (95% CI: 0.7607-0.9495, p<0.001) predicting PICU mortality and its best predictive value was >9.5 (sensitivity 75.0%, specificity 87.0%). CONCLUSION: Pediatric acute leukemia complicated with septic shock is characterized as rapid deterioration and high mortality. A pSOFA score greater than 9.5 and acute heart failure are associated with poor outcomes.

Pneumocystis jirovecii-associated immune reconstitution inflammatory syndrome-like phenomenon in a child with leukaemia: a case report and literature review.

BACKGROUND: Immune reconstitution inflammatory syndrome (IRIS) refers to the phenomenon of intense immune responses against pathogens in patients with AIDS undergoing antiretroviral therapy to reconstitute immune function, resulting in functional impairment of multiple organs. Non-AIDS immunosuppressed hosts may also develop similar manifestations to IRIS during immune recovery. CASE PRESENTATION: An 8-year-old girl presented with acute lymphoblastic leukaemia was admitted for scheduled chemotherapy treatment. During chemotherapy, she experienced pancytopenia and Pneumocystis jirovecii pneumonia, which was diagnosed based on the abnormal shadows observed on chest computed tomography, the elevation of serum ß-D-glucan, and the positive mNGS results of Pneumocystis jirovecii in both sputum and blood. After treatment with Granulocyte Colony-Stimulating Factor, sulfamethoxazole, and caspofungin, aggravation of lung lesions was discovered and severe interstitial lung disease developed in a short period along with a rapidly increasing leukocyte count. Intravenous methylprednisolone pulse therapy was given, but lung function did not improve, and she finally died after the withdrawal of medical care. CONCLUSIONS: For patients with acute lymphocytic leukaemia infected with Pneumocystis jirovecii, the rapid aggravation of pulmonary lesions in the process of blood recovery and immune reconstitution should raise vigilance against the possibility of IRIS-like reactions. The use of granulocyte stimulating factors may aggravate the inflammatory response in the lungs. The timing, dosage, and duration of treatment of glucocorticoids and the impact of high-dose methylprednisolone pulse therapy on the prognosis of patients should be explored in further research.

Bulbar conjunctival vascular lesion combined with spontaneous retrobulbar hematoma: A case report.

BACKGROUND: Orbital hemorrhage can be classified as traumatic or spontaneous depending on its cause. Spontaneous orbital hemorrhage refers to an internal orbital hemorrhage without apparent cause. Therefore, we aimed to describe a case of an orbital hematoma after a severe cough the night before due to inhalation of cooking oil fumes. CASE SUMMARY: A 46-year-old woman was referred to our hospital with a complaint of exophthalmos accompanied with blurred vision, pain, binocular diplopia, and dizziness lasting for 5 h noted on waking in the morning. She also experienced nausea and vomiting due to high pressure of orbit and dizziness. Based on the auxiliary examination and her medical history, the patient was finally diagnosed with bulbar conjunctival vascular lesion combined with spontaneous retrobulbar hematoma. The patient was administered tobramycin and dexamethasone eye ointment, and applied pressure dressing on the left eye to stop the bleeding. Simultaneously, we administered intravenous etamsylate, oral Yunnan Baiyao capsule, intravenous mannitol to reduce orbital pressure, and intravenous dexamethasone injection at 10 mg/dL combined with neurotrophic therapy to reduce tissue edema. Among them, the Yunnan Baiyao capsule is a traditional Chinese herbal medicine to remove stasis and stop bleeding; thus, it promotes blood circulation and relieves pain resulting in reduced edema of the lesion site. The symptoms did not improve significantly during the first 2 d of treatment. We speculate that high orbital pressure and binocular diplopia induced frequent nausea and vomiting in the patient, causing increased pressure on the superior vena cava and leading to repeated orbital bleeding. After the second day, the symptoms started gradually improving. CONCLUSION: This case further emphasizes the importance of comprehensive, detailed medical history and careful ophthalmic examination of the patient.

Neuromyelitis optica spectrum disorder with active replication of hepatitis B virus and seropositive anti-aquaporin-4 antibody: A case report.

RATIONALE: Neuromyelitis optica spectrum disorder (NMOSD) associated with active replication of hepatitis B virus (HBV) is rare. High-dose corticosteroids are the mainstay treatment of NMOSD; however, these may cause reactivation of viral replication in patients with stable HBV which may lead to liver damage. Therefore, care should be placed in corticosteroid use in patients with NMOSD and HBV infection. PATIENT CONCERNS: Herein, we report the case of a 31-year-old woman with NMOSD and HBV infection who was seropositive for anti-aquaporin-4 antibody. The stable and HBV carrier status of the patient led to the deferment of antiviral and hepatoprotective agents in early treatment. However, liver function impairment was detected during follow-up, with an improvement in the best-corrected visual acuity. DIAGNOSES: The patient was diagnosed with NMOSD with active replication of HBV and seropositive anti-aquaporin-4 antibody considering the medical history and ancillary examinations. INTERVENTIONS: To manage NMOSD, intravenous high-dose methylprednisolone (20 mg/kg d) was administered for 5 days which was gradually tapered to oral steroids. However, liver function impairment was observed during follow-up; therefore, anti-HBV drugs (entecavir) and hepatoprotective drugs (bicyclol or polyunsaturated phosphatidylcholine) were administered. OUTCOMES: A marked improvement was observed in the patient's best-corrected visual acuity after 4 weeks of treatment. However, follow-up examinations revealed liver function damage which necessitated administration of antiviral and hepatoprotective drugs. Liver function normalized after 1 month. LESSON: This case underscores the importance of preventive treatment of liver protection in patients with HBV infection prior to or simultaneous with glucocorticoid therapy and furthermore, there is an urgent need to develop authoritative guidelines regulating corticosteroid use in the treatment of patients with HBV infection.

Predictive risk scales for development of pressure ulcers in pediatric patients admitted to general ward and intensive care unit.

BACKGROUND: More than ten special scales are available to predict the risk of pressure ulcers in children. However, the performances of those scales have not yet been compared in China. AIM: To compare the Waterlow, Braden Q, and Glamorgan scales, and identify more suitable pressure ulcer evaluation scale for the pediatric intensive care unit (PICU). METHODS: Trained nurses used the Waterlow, Braden Q, and Glamorgan scales to assess pediatric patients at Sun Yat-sen Memorial Hospital (China) within 24 h of admission from May 2017 to December 2020 in two stages. Skin examination was carried out to identify pressure ulcers every 3 d for 3 wk. RESULTS: The incidence of pressure ulcers was 3/28 (10.7%) in the PICU and 5/314 (1.6%) in the general pediatric ward. For children in the general ward, the Waterlow, Braden Q, and Glamorgan scales had comparable area under the operating characteristic curve (AUC) of 0.870, 0.924, and 0.923, respectively, and optimal cut-off values of 14, 14, and 29 points. For PICU, the Waterlow, Braden Q, and Glamorgan scales had slightly lower AUC of 0.833, 0.733, and 0.800, respectively, and optimal cut-off values of 13, 16, and 27 points. Braden Q demonstrated a satisfactory specificity, and during the second stage of the study for PICU patients, the AUC of the Braden Q scale was 0.810, with an optimal cut-off value of 18.35 points. CONCLUSION: The Waterlow, Braden Q, and Glamorgan scales have comparable performance, while the Braden Q scale demonstrates a better specificity and can be successfully used by pediatric nurses to identify patients at high risk of pressure ulcers in PICU.

A novel common gamma chain mutation in a Chinese family with X-linked severe combined immunodeficiency (X-SCID; T(-)NK(-)B(+)).

X-linked severe combined immunodeficiency (X-SCID) is one of the most common causes of primary immunodeficiencies in humans. A 4-month-old boy with recurrent pulmonary infection had decreased numbers of CD3(+), CD4(+), CD8(+) T lymphocytes, and NK cells and increased levels of CD19(+) B cells but no memory B cells or plasma cells. The production of cytokines by T cells and the activation of T and B cells were either absent or inefficient. While B cell levels were high, they were all IgM-positive, and the secretion of all Ig isotypes by activated B cells in vitro was defective. Genomic DNA sequencing revealed that the patient had missense mutations in the IL2RG (exon 5, 718 T > C) and IL7R genes (exon 2, 197 T > C; exon 4, 412G > A). Although the patient's father and one of his sisters have the same missense homozygous mutations of the IL7R gene, neither of them exhibited the immunological phenotype of SCID. The results indicate that the IL2RG gene mutation or a combination of the IL7R and IL2RG mutations in the sick boy had resulted in T(-)NK(-)B(+) SCID.