Transformation of Black Phosphorus through Lattice Reconstruction for NIR-II-Responsive Cancer Therapy.

The photothermal performance of black phosphorus (BP) in the near infrared (NIR)-II bio-window (1000-1500 nm) is low, which limits its biomedical applications. Herein, ultrasmall nickel phosphide quantum dots (Ni2 P QDs) are synthesized with BP quantum dots (BPQDs) as the template by topochemical transformation. The size of Ni2 P QDs is ≈3.5 nm, similar to that of BPQDs, whereas the absorption and photothermal conversion efficiency of Ni2 P QDs at 1064 nm (43.5%) are significantly improved compared with those of BPQDs. To facilitate in vivo applications, an Ni2 P QDs-based liposomal nano-platform (Ni2 P-DOX@Lipo-cRGD) is designed by incorporation of Ni2 P QDs and doxorubicin (DOX) into liposomal bilayers and the interior, respectively. The encapsulated DOX is responsively released from liposomes upon 1064-nm laser irradiation owing to the photothermal effect of Ni2 P QDs, and the drug release rate and amount are controlled by the light intensity and exposure time. In vivo, experiments show that Ni2 P-DOX@Lipo-cRGD has excellent tumor target capability and biocompatibility, as well as complete tumor ablation through the combination of photothermal therapy and chemotherapy. The work provides a new paradigm for the NIR-II transformation of nano-materials and may shed light on the construction of multifunctional nano-platforms for cancer treatment.

Moxibustion with Walnut Shell Spectacles Could Improve the Objective Symptoms and Tear Film Stability of Patients with Dry Eye Disease: A Randomized Controlled Trial.

Objectives: This study aims to evaluate the efficacy and acceptability of moxibustion with walnut shell spectacles in treating dry eye disease (DED) patients and to provide treatment options. Methods: 126 DED patients were randomly allocated into the moxibustion group (treated by moxibustion with walnut shell spectacles, 64 cases) and the artificial tears group (treated with sodium hyaluronate eye drops, 62 cases). Evaluate the changes in the ocular surface disease index (OSDI), the visual analogue scale (VAS) of ocular discomfort, the tear film break-up time (TBUT), corneal fluorescein staining (CFS), and the Schirmer I test during the trial at baseline and after 1-week, 2-week, 3-week, and 4-week treatment. Evaluate the OSDI scale and the ocular symptom VAS scale one month after the end of treatment. Results: There were no significant differences in baseline characteristics between the two groups. For OSDI scores, the results showed that the efficacy of the moxibustion group was no less than that of the artificial tear group. For VAS of ocular discomfort, both groups significantly reduced their score compared with baseline, and for the moxibustion group, the decrease was more significant. For TBUT, FAS, and PPS, results showed that the efficacy of the moxibustion group was significant in both eyes after 4 weeks of treatment, but the right eye was in the artificial tear group. For CFS and Schirmer I test scores, there was no significant effect for both groups. Conclusion: Moxibustion with walnut shell spectacles could improve the clinical symptoms and tear film stability of DED patients; however, it has no significant efficacy on improving corneal injury and tear secretion, just the same as sodium hyaluronate eye drops. Nevertheless, moxibustion with walnut shell spectacles may have better effects on the self-assessment of ocular discomfort than sodium hyaluronate eye drops.

Black phosphorous nanosheet: A novel immune-potentiating nanoadjuvant for near-infrared-improved immunotherapy.

Intrinsic immune behaviors of nanomaterials and immune systems promote research on their adjuvanticity and the design of next generation nanovaccine-based immunotherapies. Herein, we report a promising multifunctional nanoadjuvant by exploring the immune-potentiating effects of black phosphorus nanosheets (BPs) in vitro and in vivo. The facile coating of BPs with phenylalanine-lysine-phenylalanine (FKF) tripeptide-modified antigen epitopes (FKF-OVAp@BP) enables the generation of a minimalized nanovaccine by integrating high loading capacity, efficient drug delivery, comprehensive dendritic cell (DC) activation, and biocompatibility for cancer immunotherapy. Systemic immunization elicits potent antitumor cellular immunity and significantly augments checkpoint blockade (CPB) against melanoma in a mouse model. Furthermore, near-infrared (NIR) photothermal effects of BPs create an immune-favorable microenvironment for improved local immunization. This study offers new insight into the integration of immunoactivity and photothermal effects for enhanced cancer immunotherapy by using a nanoadjuvant and thus potentially advances the design and application of multifunctional adjuvant materials for cancer nanotreatment.

Sensitive and selective ctDNA detection based on functionalized black phosphorus nanosheets.

Circulating tumor DNA (ctDNA) identification is one of the most meaningful approaches towards early cancer diagnosis. However, effective and practical methods for analyzing this emerging class of biomarkers are still lacking. In this work, a biosensor based on nitrophenyl functionalized black phosphorus nanosheets (NP-BPs) is fabricated for sensitive and selective detection of ctDNA. In this work, a nitrophenyl functionalized black phosphorus nanosheets (NP-BPs) biosensor is fabricated for sensitive and selective detection of ctDNA. Due to the successful nitrophenyl functionalization, the NP-BPs biosensor shows higher quenching efficiency and stronger affinity towards single-stranded DNA (ssDNA), as compared with double-stranded DNA (dsDNA). Therefore, the NP-BPs biosensor exhibits 5.4-fold fluorescence enhancement when dye-labelled ssDNA probe forms dsDNA in the presence of its specific ctDNA target. This biosensor exhibits a detection limit of 50 fM and a wide linear detection range of 50 fM-80 pM, provides reliable readout in a short time (15 min). Moreover, the NP-BPs-based biosensor could be applied to discriminate single nucleotide polymorphisms in clinical serum samples. It is envisioned that the NP-BPs-based sensing platform has great potentials in early cancer diagnosis and monitoring cancer progression.

Bioactive phospho-therapy with black phosphorus for in vivo tumor suppression.

Background and Purpose: Although inorganic nanomaterials have been widely used in multimodal cancer therapies, the intrinsic contributions of the materials are not well understood and sometimes underestimated. In this work, bioactive phospho-therapy with black phosphorus nanosheets (BPs) for in vivo tumor suppression is studied. Methods: Orthotopic liver tumor and acute myeloid leukemia are chosen as the models for the solid tumor and hematological tumor, respectively. BPs are injected into mice through the tail vein and tumor growth is monitored by IVIS bioluminescence imaging. Tumor tissues and serum samples are collected to determine the suppression effect and biosafety of BPs after treatment. Results: The in vitro studies show that BPs with high intracellular uptake produce apoptosis- and autophagy-mediated programmed cell death of human liver carcinoma cells but do not affect normal cells. BPs passively accumulate in the tumor site at a high concentration and inhibit tumor growth. The tumor weight is much less than that observed from the doxorubicin (DOX)-treated group. The average survival time is extended by at least two months and the survival rate is 100% after 120 days. Western bolt analysis confirms that BPs suppress carcinoma growth via the apoptosis and autophagy pathways. In addition, administration of BPs into mice suffering from leukemia results in tumor suppression and long survival. Conclusions: This study reveals that BPs constitute a type of bioactive anti-cancer agents and provides insights into the application of inorganic nanomaterials to cancer therapy.

Synthesis of lipid-black phosphorus quantum dot bilayer vesicles for near-infrared-controlled drug release.

Black phosphorus quantum dots are incorporated into liposomal bilayers to produce a drug delivery system with excellent near-infrared (NIR) photothermal properties and drug release capability controlled by light. In vitro experiments demonstrate its good biocompatibility and NIR-light-induced chemo-photothermal antitumor efficiency.

[Walnut-shell moxibustion for dry eye symptoms: a randomized controlled trial].

OBJECTIVE: To evaluate the effects of walnut-shell moxibusiton on dry eye symptoms. METHODS: A total of 67 patients with dry eye symptoms were randomized into a walnut moxibustion group and a sodium hyaluronate eye drops group. METHODS: In the walnut moxibustion group, the walnut moxibustion was used, once every two days, 3 times a week, for 4 weeks totally. In the sodium hyaluronate eye drops group, sodium hyaluronate eye drops were selected, 4 times a day, one drop instilled in each eye each time, for 4 weeks totally. At the baseline (before treatment) and in 4 weeks of treatment, the score of the ocular surface disease index (OSDI), the score of visual analogous scale (VAS) for eye symptoms, the tear film break-up time (BUT), the cornea fluorescent pigmentation (FL) and SchirmerⅠ(SchⅠ) were evaluated. In 1-month follow-up after treatment termination, the changes of OSDI and VAS scores were evaluated in the two groups. RESULTS: In 4 weeks of treatment and the follow-up, OSDI scores were reduced as compared with those before treatment in the two groups (P<0.001, P<0.05). In 4 weeks of treatment and the follow-up, the change values of OSDI were (-16.03±17.42) and (-13.47±21.41) as compared with those before treatment in the walnut moxibustion group; and were (-9.58±23.45) and (-13.90±20.92) in the sodium hyaluronate eye drops group separately. The differences were not significant between the two groups (all P>0.05). In 4 weeks of treatment and the follow-up, VAS scores were reduced as compared with those before treatment in the two groups (all P<0.001). In 4 weeks of treatment, BUT was increased as compared with that before treatment in the two groups (both P<0.05), the results of FL and SchⅠ did not change significantly before and after treatment in the two groups (all P>0.05). The differences were not significant in the above indexes between the two groups (all P>0.05). There was no obvious adverse reaction in the two groups. CONCLUSION: The walnut-shell moxibustion is available likely for the subjective symptoms in the patients with dry eye syndrome and contributes to the tear film stabilization. The therapeutic effects need to be further evaluated with the adequate sample size in the randomized controlled trial.

The effectiveness and safety of a danshen-containing Chinese herbal medicine for diabetic retinopathy: a randomized, double-blind, placebo-controlled multicenter clinical trial.

ETHNOPHARMACOLOGICAL RELEVANCE: Salvia miltiorrhiza (Danshen in Chinese) is a common traditional Chinese herbal medicine often used to treat many medical conditions. The Compound Danshen Dripping Pill (CDDP) is a danshen-containing Chinese herbal product for the treatment of cardiovascular diseases. However, to date, no controlled clinical studies have been conducted to evaluate the effects of CDDP on diabetic retinopathy (DR). AIM OF THE STUDY: The present large-scale clinical trial was designed to assess the effectiveness and safety of CDDP in treating patients with non-proliferative diabetic retinopathy (NPDR). MATERIALS AND METHODS: 223 NPDR patients were enrolled in this controlled trial. Subjects received oral study medications three times daily for 24 weeks. The four groups were placebo, low-dose (270 mg), mid-dose (540 mg) and high dose (810 mg herbal medicine). Primary endpoints were changes in fluorescence fundus angiography (FFA) and fundoscopic examination parameters. RESULTS AND DISCUSSION: At 24 weeks, for the FFA, the percent of "Excellent" and "Effective" in the high-dose and mid-dose CDDP groups was 74% and 77%, respectively, very significantly higher than 28% in the placebo group (P<0.001). For fundoscopic examination, the percent of "Excellent" and "Effective" in the high-dose and mid-dose CDDP groups was 42% and 59%, respectively, very significantly higher than 11% in the placebo group (P<0.001). No adverse events with clinical significance were observed. CONCLUSIONS: DR is a severe microvascular complication of diabetes and a major cause of adult blindness worldwide. Our clinical trial data demonstrated the therapeutic value and safety of a danshen-containing Chinese herbal medicine in patients with diabetic retinopathy.

[Clinical study on electrical plum-blossom needle for treatment of amblyopia in children].

OBJECTIVE: To comparatively study the clinical effect of electrical plum-blossom needle on ametropic amblyopia and anisometropic amblyopia. METHODS: Sixty children (107 eyes) with ametropic amblyopia or anisometropic amblyopia were randomly assigned to two groups at their first visit on the basis of optometry. They had never received any treatment before. Patients in one group were treated with electrical plum-blossom needle (as the treatment group) and those in the other group were treated with physical comprehensive therapy (as the control group). The 1-month clinical effect was observed. RESULTS: The 1-month total effective rate was 79.6% (43/54) in the treatment group and 58.5% (31/53) in the control group. Statistical significance was shown in clinical effect after statistical management. The electrical plum-blossom needle showed better effect than the comprehensive therapy. CONCLUSION: The electrical plum-blossom needle for treatment of amblyopia in children could initiate faster with good compliance. Its short-term effect was definite with no side effect.

Current management of intracerebral haemorrhage in China: a national, multi-centre, hospital register study.

BACKGROUND: We aimed to examine current practice of the management and secondary prevention of intracerebral haemorrhage (ICH) in China where the disease is more common than in Western populations. METHODS: Data on baseline characteristics, management in-hospital and post-stroke, and outcome of ICH patients are from the ChinaQUEST (QUality Evaluation of Stroke Care and Treatment) study, a multi-centre, prospective, 62 hospital registry in China during 2006-07. RESULTS: Nearly all ICH patients (n = 1572) received an intravenous haemodiluting agent such as mannitol (96%) or a neuroprotectant (72%), and there was high use of intravenous traditional Chinese medicine (TCM) (42%). Neurosurgery was undertaken in 137 (9%) patients; being overweight, having a low Glasgow Coma Scale (GCS) score on admission, and Total Anterior Circulation Syndrome (TACS) clinical pattern on admission, were the only baseline factors associated with this intervention in multivariate analyses. Neurosurgery was associated with nearly three times higher risk of death/disability at 3 months post-stroke (odd ratio [OR] 2.60, p < 0.001). Continuation of antihypertensives in-hospital and at 3 and 12 months post-stroke was reported in 732/935 (78%), 775/935 (83%), and 752/935 (80%) living patients with hypertension, respectively. CONCLUSIONS: The management of ICH in China is characterised by high rates of use of intravenous haemodiluting agents, neuroprotectants, and TCM, and of antihypertensives for secondary prevention. The controversial efficacy of these therapies, coupled with the current lack of treatments of proven benefit, is a call for action for more outcomes based research in ICH.

Age and gender variations in the management of ischaemic stroke in China.

BACKGROUND: Stroke is a major health issue in China. AIMS: We aimed to describe the management of patients admitted to hospitals in China with acute ischaemic stroke, and to determine whether there were any differences by age and gender. METHODS: Using a multicentre prospective hospital register across all eight major economic (geographic) regions in China, data on the socioeconomic characteristics, medical history, clinical features, and in-hospital investigations, management, and outcomes were collected on consecutive patients with acute stroke due to cerebral ischaemia during a 5-month period in 2006. RESULTS: Overall, traditional Chinese medicine and neuroprotectant use were remarkably high, with nearly 80% of patients receiving the former and >70% receiving the latter in hospital. Length of hospital stay was also long (median duration 16-days). Multivariate analyses revealed no clinically important differences in management between the genders. For the age-specific analyses, there were significant trends of decreasing use of thrombolysis (P=0·04), warfarin (P=0·01), corticosteroids (P=0·03), and lipid-lowering therapy (P=0·001); however, more assisted feeding (P=0·004) and rising rates of disability and in-hospital complications occurred with increasing age. CONCLUSIONS: New information is provided regarding the current state of ischaemic stroke management in China. Notably, there is high use of traditional Chinese medicine and neuroprotectants and long lengths of hospital stay. Similar to many other countries, differences in stroke care and management by age and gender also exist to a small extent in China.

Effect of qiming granule on retinal blood circulation of diabetic retinopathy: a multicenter clinical trial.

OBJECTIVE: To objectively assess the effect of Qiming Granule in the treatment of diabetic retinopathy (DR) by fluorescence fundus angiography (FFA). METHODS: In a multi-center, randomized, parallel controlled clinical trial, patients with DR were randomly assigned to the control group (calcium dobesilate capsule) and the test group (Qiming Granule). Changes in the retinal blood circulation time were recorded by FFA after 3 months of medication. RESULTS: Significant reduction was observed in the retinal arterio-venous circulation time (AVCT) in both groups (P<0.01), the value was 7.635+/-3.149 s before treatment and 5.165 +/-3.382 s after treatment in the treated group, and 7.737+/-3.413 s and 5.313+/-3.472 s in the control group respectively. Qiming Granule also reduced the arm-to-retinal circulation time (ARCT, P<0.05). The value was 17.867+/-3.872 s before treatment and 15.643+/-4.648 s after treatment in the treated group, and 17.217+/-3.833 s and 16.312+/-3.613 s in the control group (P>0.05) respectively. The ARCT in the tested group was reduced, with a statistically significant difference post-medication (P<0.01). CONCLUSION: As a Chinese medicine complex prescription, Qiming Granule may alleviate retinal hypoxia and ischemia by increasing retinal blood flow and improving the blood circulation.