Atomically precise photothermal nanomachines.

Interfacing molecular machines to inorganic nanoparticles can, in principle, lead to hybrid nanomachines with extended functions. Here we demonstrate a ligand engineering approach to develop atomically precise hybrid nanomachines by interfacing gold nanoclusters with tetraphenylethylene molecular rotors. When gold nanoclusters are irradiated with near-infrared light, the rotation of surface-decorated tetraphenylethylene moieties actively dissipates the absorbed energy to sustain the photothermal nanomachine with an intact structure and steady efficiency. Solid-state nuclear magnetic resonance and femtosecond transient absorption spectroscopy reveal that the photogenerated hot electrons are rapidly cooled down within picoseconds via electron-phonon coupling in the nanomachine. We find that the nanomachine remains structurally and functionally intact in mammalian cells and in vivo. A single dose of near-infrared irradiation can effectively ablate tumours without recurrence in tumour-bearing mice, which shows promise in the development of nanomachine-based theranostics.

Sandwich-Structured Implants to Obstruct Multipath Energy Supply and Trigger Self-Enhanced Hypoxia-Initiated Chemotherapy Against Postsurgical Tumor Recurrence and Metastasis.

As a currently common strategy to treat cancer, surgical resection may cause tumor recurrence and metastasis due to residual postoperative tumors. Herein, an implantable sandwich-structured dual-drug depot is developed to trigger a self-intensified starvation therapy and hypoxia-induced chemotherapy sequentially. The two outer layers are 3D-printed using a calcium-crosslinked mixture ink containing soy protein isolate, polyvinyl alcohol, sodium alginate, and combretastatin A4 phosphate (CA4P). The inner layer is one patch of poly (lactic-co-glycolic acid)-based electrospun fibers loaded with tirapazamine (TPZ). The preferentially released CA4P destroys the preexisting blood vessels and prevents neovascularization, which obstructs the external energy supply to cancer cells but aggravates hypoxic condition. The subsequently released TPZ is bioreduced to cytotoxic benzotriazinyl under hypoxia, further damaging DNA, generating reactive oxygen species, disrupting mitochondria, and downregulating hypoxia-inducible factor 1α, vascular endothelial growth factor, and matrix metalloproteinase 9. Together these processes induce apoptosis, block the intracellular energy supply, counteract the disadvantage of CA4P in favoring intratumor angiogenesis, and suppress tumor metastasis. The in vivo and in vitro results and the transcriptome analysis demonstrate that the postsurgical adjuvant treatment with the dual-drug-loaded sandwich-like implants efficiently inhibits tumor recurrence and metastasis, showing great potential for clinical translation.

Treating patients infected with the SARS-CoV-2 Omicron variant with a traditional Chinese medicine, Shufeng Jiedu capsule.

Patients infected with the Omicron variant of SARS-CoV-2 mainly develop mild COVID-19, manifesting as upper respiratory symptoms, fatigue, and fever. Shufeng Jiedu capsule (SFJDC), a traditional Chinese medicine indicated for treatment of upper respiratory infections in China, was tested for its efficacy and safety in treatment of an Omicron infection at a mobile cabin hospital in response to an outbreak of COVID-19 in Shanghai, China in April 2022. In this open-label, randomized controlled trial, patients in the control group received best supportive care, while those in the test group received additional SFJDC therapy for 7 days. SFJDC markedly alleviated patients' symptoms including a sore throat, coughing, fatigue, and a fever after 7 days of treatment. The virus negative time was significantly shorter in the SFJDC treatment group, but there were no obvious differences in the virus negative rate between the two groups at the end of the 7-day follow-up. These results suggest that patients with the Omicron infection may benefit from SFJDC treatment. Double-blind, randomized controlled trials are warranted to comprehensively evaluate the efficacy and safety of SFJDC in a large cohort study in the future.

3D Printed Bioceramic Scaffolds as a Universal Therapeutic Platform for Synergistic Therapy of Osteosarcoma.

The postoperative tumor recurrence and chemotherapy resistance in clinical osteosarcoma treatment have raised an imperative need to develop local implants for selectively killing residual tumor cells and simultaneously provide a scaffold for effectively filling the tumor resection-induced bone defects. Herein, a multifunctional platform is developed through successively coating TiN microparticles and doxorubicin (DOX) on the surface of tricalcium phosphate (TCP) scaffolds to achieve synergetic effects of photothermal therapy and chemotherapy for osteosarcoma. The content of TiN and DOX in the scaffolds can be flexibly adjusted by immersing the scaffolds into the solution containing different concentrations of TiN and DOX. The excellent therapeutic effect was achieved both in vitro and in vivo through the precise photothermal therapy and localized controlled-release chemotherapy. Moreover, the overall bulk scaffolds provide the mechanical support for bone tissue when implanting scaffolds into bone defects resulting from surgical removal of osteosarcoma. Importantly, using the poly(d,l-lactide) (PDLLA) as the medium, the scaffolds can be exploited as a universal platform for loading different kinds of therapeutic agents. This study may provide insights into designing multifunctional local implantation for eradicating tumors after surgical interventions with mitigated side effects.

[Acupuncture at Ciliao (BL 32) for prevention of postpartum urinary retention in elderly parturient women: a randomized controlled trial].

OBJECTIVE: To explore the preventive effect of acupuncture at Ciliao (BL 32) on postpartum urinary retention as well as the time and volume of the first urination after delivery in elderly parturient women undergoing vaginal delivery. METHODS: A total of 180 elderly parturient women (≥35 years old) undergoing vaginal delivery were randomly divided into a blank control group, a conditional control group and an observation group, 60 cases in each group. The patients in the blank control group were treated with routine nursing plan; based on the treatment of the blank control group, the patients in the conditional control group were treated with additional intervention measures such as applying hot towel on the bladder and fingers pressing to stimulate urination; based on the treatment of the blank control group, the patients in the observation group were treated with acupuncture at bilateral Ciliao (BL 32) one hour after delivery for 20 min (the acupuncture was given only once). The incidence rate of postpartum urinary retention as well as the time and volume of the first urination among the women without urinary retention were observed; the satisfaction rate of the 3 groups was recorded. RESULTS: The incidence rate of postpartum urinary retention in the observation group was 5.0% (3/60), which was significantly lower than 26.7% (16/60) in the blank control group (P<0.01) and 16.7% (10/60) in the conditional control group (P<0.05); the incidence rate of postpartum urinary retention in the conditional control group was significantly lower than that in the blank control group [16.7% (10/60) vs 26.7%(16/60), P<0.05]. In the elderly women without urinary retention, the first urination time in the observation group was significantly earlier than that in the blank control group and conditional control group (P<0.01), and the first urination time in the conditional control group was earlier than that in the blank control group (P<0.01). The volume of first urination in the observation group was higher than that in the blank control group and the conditional control group (P<0.05, P<0.01). The satisfaction rates in the observation group and conditional control group were higher than that in the blank control group (P<0.01). CONCLUSION: Acupuncture at Ciliao (BL 32) could effectively prevent the postpartum urinary retention, improve the time and volume of the first urination in elderly parturient women undergoing vaginal delivery.

Shape-controlled magnetic mesoporous silica nanoparticles for magnetically-mediated suicide gene therapy of hepatocellular carcinoma.

Magnetic nanoparticles (NPs) have emerged as a promising tool for suicide gene therapy. However, the separate delivery of the suicide gene and prodrug in current systems limits their clinical translation. Therefore, improving magnetically mediated suicide gene therapy by exploring higher performance magnetic NP-based hybrid nanoplatforms is an important challenge. In the current study, shape-controlled magnetic mesoporous silica nanoparticles (M-MSNs) were prepared, and their performance in magnetic resonance imaging (MRI)-guided, magnetically targeted and hyperthermia-enhanced suicide gene therapy of hepatocellular carcinoma (HCC) was investigated. Compared with sphere-like MSNs, rod-like MSNs exhibited higher loading capacity, faster prodrug release behavior, stronger magnetically enhanced gene delivery and better magnetic hyperthermia properties. Utilizing the improved magnetic properties of the M-MSNs allowed us to demonstrate highly effective dual magnetically enhanced suicide gene therapy in vivo with decreased systematic toxicity and with the ability to monitor therapeutic outcome by MRI. Because of their magnetic targeting abilities, magnetic hyperthermia performance and MRI properties, these M-MSNs might prove to be a potentially superior candidate for suicide gene therapy of HCC.

Assessing levels and trends of child health inequality in 88 developing countries: from 2000 to 2014.

BACKGROUND: Reducing child mortality was one of the Millennium Development Goals. In the current Sustainable Development Goals era, achieving equity is prioritized as a major aim. OBJECTIVE: This study aims to provide a comprehensive and updated picture of inequalities in child health intervention coverage and child health outcomes by wealth status, as well as their trends between 2000 and 2014. METHODS: Using data from Demographic Health Surveys and Multiple Indicator Cluster Surveys, we adopted three measures of inequality, including one absolute inequality indicator and two relative inequality indicators, to estimate the level and trends of inequalities in three child health outcome variables and 17 intervention coverages in 88 developing countries. RESULTS: While improvements in child health outcomes and coverage of interventions have been observed between 2000 and 2014, large inequalities remain. There was a high level of variation between countries' progress toward reducing child health inequalities, with some countries significantly improving, some deteriorating, and some remaining statistically unchanged. Among child health interventions, the least equitable one was access to improved sanitation (The absolute difference in coverages between the richest quintile and the poorest quintile reached 49.5% [42.7, 56.2]), followed by access to improved water (34.1% [29.5, 38.6]), and skilled birth attendant (SBA) (34.1% [28.8, 39.4]). The most equitable intervention coverage was insecticide-treated bed net for children (1.0% [-3.9, 5.9]), followed by oral rehydration therapy for diarrhea ((8.0% [5.2, 10.8]), and vitamin A supplement (8.4% [5.1, 11.7]). These findings were robust to various inequality measurements. CONCLUSIONS: Although child health outcomes and coverage of interventions have improved largely over the study period for almost all wealth quintiles, insufficient progress was made in reducing child health inequalities between the poorest and richest wealth quintiles. Future efforts should focus on reaching the poorest children by increasing investments toward expanding the coverage of interventions in resource-limited settings.

Janus Silver/Silica Nanoplatforms for Light-Activated Liver Cancer Chemo/Photothermal Therapy.

Stimuli-triggered nanoplatforms have become attractive candidates for combined strategies for advanced liver cancer treatment. In this study, we designed a light-responsive nanoplatform with folic acid-targeting properties to surmount the poor aqueous stability and photostability of indocyanine green (ICG). In this Janus nanostructure, ICG was released on-demand from mesoporous silica compartments in response to near-infrared (NIR) irradiation, exhibiting predominant properties to convert light to heat in the cytoplasm to kill liver cancer cells. Importantly, the silver ions released from the silver compartment that were triggered by light could induce efficient chemotherapy to supplement photothermal therapy. Under NIR irradiation, ICG-loaded Janus nanoplatforms exhibited synergistic therapeutic capabilities both in vitro and in vivo compared with free ICG and ICG-loaded mesoporous silica nanoparticles themselves. Hence, our Janus nanoplatform could integrate ICG-based photothermal therapy and silver ion-based chemotherapy in a cascade manner, which might provide an efficient and safe strategy for combined liver cancer therapy.

Berberine-loaded Janus nanocarriers for magnetic field-enhanced therapy against hepatocellular carcinoma.

Berberine, an bioactive isoquinolin alkaloid from traditional Chinese herbs, is considered to be a promising agent based on its remarkable activity against hepatocellular carcinoma. However, the clinical application of this nature compound had been hampered owing to its properties such as poor aqueous solubility, low gastrointestinal absorption, and reduced bioavailability. Therefore, we developed Janus magnetic mesoporous silica nanoparticles (Fe3 O4 -mSiO2 NPs) consisting of a Fe3 O4 head for magnetic targeting and a mesoporous SiO2 body for berberine delivery. A pH-sensitive group was introduced on the surface of mesoporous silica for berberine loading to develop a tumor microenvironment-responsive nanocarrier, which exhibited uniform morphology, good superparamagnetic properties, high drug-loading amounts, superior endocytic ability, and low cytotoxicity. Berberine-loaded Fe3 O4 -mSiO2 NPs exerted extraordinarily high specificity for hepatocellular carcinoma cells, which was due to the pH-responsive berberine release, as well as higher endocytosis capacity in hepatocellular carcinoma cells rather than normal liver cells. More importantly, an external magnetic field could significantly improve antitumor activity of Ber-loaded Fe3 O4 -mSiO2 NPs through enhancing berberine internalization. Taken together, our results suggest that Janus nanocarriers driven by the magnetic field may provide an effective and safe way to facilitate clinical use of berberine against hepatocellular carcinoma.

Application of controlled hypotension combined with autotransfusion in spinal orthomorphia.

BACKGROUND: Idiopathic scoliosis is a common spinal deformity in teenagers, which is managed mainly by orthomorphia. However, due to great trauma, long operative duration and large blood loss, a great amount of blood transfusion is needed during the surgery. Allogeneic blood transfusion should be reduced in order to release blood insufficient, decline blood transfusion expense, as well as avoid transfusion diseases. OBJECTIVE: The objective of the following study is to investigate the value of controlled hypotension combined with autotransfusion in idiopathic scoliosis orthomorphia and in order to reduce surgical bleeding and reduction in blood transfusion. SUBJECTS AND METHODS: Intra-operative controlled hypotension was performed during posterior orthomorphia surgery on all the 46 cases of idiopathic scoliosis, 17 cases in which were served as the control group, who underwent allogeneic blood transfusion without autotransfusion, whereas the other 29 cases were served as the experimental group, who underwent autotransfusion that including reinfusion of pre-operative deposited autologous blood and intra-operative salvaged autologous blood. The blood loss volume and transfusion status in two groups were observed. RESULTS AND CONCLUSION: Blood loss volume in the control group was 400-1000 (835.3 ± 167.5) mL and that in the experimental group was 350-1400 (812.1 ± 152.7) mL, there was no marked difference between the two groups (P > 0.05). The volume of allogeneic blood transfusion in the control group was 500-1800 (855.9 ± 321.1) mL, which was greater than that in the experimental group ((0-1300 (337.9 ± 258.3) mL) (P < 0.01). The results suggested that controlled hypotension reduces intraoperative bleeding and post-operative autotransfusion minimizes the need of allogeneic blood transfusion.