Mesoporous carbon nanoparticles embedded with iron in hydrogen-photothermal synergistic therapy.

We developed a new method to synthesize polyethylene glycol modified ultra small iron embedded in mesoporous carbon nanoparticle (C/Fe-PEG NP) for hydrogen (H2) assisted photothermal synergistic therapy. Herein, we use a simple in-situ reduction method to obtain the C/Fe NP in one-step carbonizing process, which is further modified by the biocompatible polyethylene glycol (PEG) on the surface of C/Fe NP to acquire high stability in physiological solutions. Utilizing the excellent photothermal property from the mesoporous carbon and the controllable H2 release property in the weakly acidic tumor microenvironment by the ultra-small Fe, the obtained C/Fe-PEG NPs can effective kill the cancer cells, meanwhile, protect normal cells without drugs. This selective anti-cancer mechanism of C/Fe-PEG NPs may because the produced H2 selective change the mitochondrial energy metabolism. In vivo results prove that the C/Fe-PEG NPs achieve excellent tumor ablation therapeutic effect and normal tissue protecting ability benefit from the H2-assisted photothermal therapy, promising the use of novel nanomaterials with more safety method for future cancer therapy.

Active Targeted Janus Theranostic Nanoplatforms Enable Chemo-Photothermal Therapy to Inhibit the Growth of Breast Cancer.

Nanoscale structures have been developed to serve various functions in cancer therapy, encompassing areas such as diagnosis, biomedical visualization, tissue regeneration, and drug delivery. Based on biocompatible chitosan oligosaccharides (COS) and gold nanorods (GNRs), we designed the drug delivery systems (GNR@polyacrylic acid-Mn@COS Janus nanoparticles (JNPs)), which achieved paclitaxel (PTX) loaded on the side of GNRs, and the PAA-Mn domain served as magnetic resonance imaging contrast agents. This system was found to be effectively delivered to tumor sites through the enhanced permeability and retention (EPR) effect and the active target of the COS. The uniform JNPs selectively targeted cancer cells instead of normal cells through interacting with the COS on the surface of tumor cells, and the pH/NIR-responsive drug release behavior further enhanced their therapeutic effects. The in vivo effects of JNPs against tumors were evaluated using subcutaneous and orthotopic lung metastasis models, yielding promising outcomes for both tumor diagnosis and cancer treatment. In conclusion, the obtained JNPs hold great promise as a theranostic nanoplatform with synergistic chemotherapeutic and photothermal effects.

Intense pulsed light treatment in meibomian gland dysfunction: Past, present, and future.

Dry eye disease is a highly prevalent condition, which can substantially impair quality of life, work productivity, and vision. It is considered an inflammatory disease and the most common cause is meibomian gland dysfunction. Despite many treatment alternatives being available, including artificial tears, warm compresses, antibiotics, and anti-inflammatory therapy, lasting treatment effects are rare. Over the last two decades, intense pulsed light therapy, after being well established in dermatology, has been gradually introduced to the field of ophthalmology to treat meibomian gland dysfunction. The purpose of the current article is to critically review the clinical studies assessing the use of intense pulsed light to treat meibomian gland dysfunction published to date. The vast majority of the included studies demonstrated improved symptoms and signs, although the degree of efficacy and its duration varied greatly depending on concomitant treatment, number of treatment sessions, and other factors. Several possible mechanisms of action concerning disease propagation and treatment efficacy are discussed. There is still a need for larger, randomised, longitudinal studies to define the most efficacious treatment regime and to predict which patients may benefit the most. More studies are needed on implementing biochemical analyses and machine learning algorithms. Such studies may prove beneficial in predicting treatment effects, defining optimal treatment regimens, and furthering our understanding of the mechanisms of action.

Value of Combined Bone Morphogenetic Protein-2/7 Testing in the Assessment of Infected Preterm Labor.

Objective: To analyze the clinical significance of bone morphogenetic protein-2 (BMP-2) and bone morphogenetic protein-7 (BMP-7), members of the bone morphogenetic protein family, in infectious preterm birth, to provide references for future prevention and management of IPB. Methods: The study participants were 20 pregnant women with IPB admitted to between January 2022 and January 2023 (research group) and 20 concurrent normal pregnancies (control group). Serum BMP2, BMP-7 inflammatory factors were quantified. Differences in BMP2 and BMP-7 were identified. The Receiver Operating Characteristic curve analyzed the evaluation value of BMP2 and BMP-7 on infectious preterm birth and adverse pregnancy outcomes in pregnant women, and Pearson correlation coefficient determined the correlation of the two with inflammatory factors levels. Results: The research group was higher in serum BMP2 and BMP-7 levels than control group (P < .05). The joint detection by BMP2 and BMP-7 had a sensitivity of 80.00% and a specificity of 90.00% in diagnosing infectious preterm birth (P < .05), and its sensitivity and specificity in predicting adverse pregnancy outcomes in infectious preterm birth pregnant women were 100.0% and 66.67%, respectively (P < .05). According to Pearson correlation coefficient analysis, there was an obvious positive relationship between BMP-2 and BMP-7 and inflammatory factors in research group (P < .05). Conclusions: BMP-2 and BMP-7 are elevated in IPB and are linked to inflammatory factor levels. Joint detection of BMP2 and BMP-7 shows promising potential for evaluating infectious preterm birth.

PD-L1 Blockade Peptide-Modified Polymeric Nanoparticles for Oxygen-Independent-Based Hypoxic Tumor Photo/Thermodynamic Immunotherapy.

Distant metastasis of malignant tumors is considered to be the main culprit for the failure of current antitumor treatments. Conventional single treatments often exhibit limited efficacy in inhibiting tumor metastasis. Therefore, there is a growing interest in developing collaborative antitumor strategies based on photothermal therapy (PTT) and free-radical-generated photodynamic therapy (PDT), especially utilizing oxygen-independent nanoplatforms, to address this challenge. Such antitumor strategies can enhance the therapeutic outcomes by ensuring the cytotoxicity of free radicals even in the hypoxic tumor microenvironment, thereby improving the effective suppression of primary tumors. Additionally, these approaches can stimulate the production of tumor-associated antigens and amplify the immunogenic cell death (ICD) effects, potentially feasible for enhancing the therapeutic outcomes of immunotherapy. Herein, we fabricated a functional nanosystem that co-loads IR780 and 2,2'-azobis[2-(2-imidazolin-2-yl)propane]-dihydrochloride (AIPH) to realize PTT-triggered thermodynamic combination therapy via the oxygen-independent pathway for the elimination of primary tumors. Furthermore, the nanocomposites were surface-decorated with a predesigned complex peptide (PLGVRGC-anti-PD-L1 peptide, MMP-sensitive), which facilitated the immunotherapy targeting distant tumors. Through the specific recognition of matrix metalloproteinase (MMP), the sensitive segment on the obtained aNC@IR780A was cleaved. As a result, the freed anti-PD-L1 peptide effectively blocked immune checkpoints, leading to the infiltration and activation of T cells (CTLs). This nanosystem was proven to be effective at inhibiting both primary tumors and distant tumors, providing a promising combination strategy for tumor PTT/TDT/immunotherapy.

Designed synthesis of prussian blue@Cu-doped zinc phosphate nanocomposites for chemo/chemodynamic/photothermal combined cancer therapy.

Designing a multifunctional nanoplatform that combines multiple treatments has emerged as an innovative cancer treatment strategy. A simple and clear route is put forward to develop Cu2+-doped zinc phosphate coated prussian blue nanoparticles (designated as PB@Cu2+/ZnP NPs) integrating tri-modal therapy (chemo, chemodynamic and photothermal therapy) for maximizing anti-tumor efficacy. The obtained PB@Cu2+/ZnP NPs possess drug loading capacity due to the mesoporous structure present in the Cu2+-doped ZnP shell. In addition, the Cu2+-doped ZnP shell can gradually degrade in response to the mildly acidic tumor microenvironment to release DOX and Cu2+, where the released drug plays the role of chemotherapy agent and the Cu2+ can react with intracellular glutathione to achieve a Cu-mediated Fenton-like reaction for chemodynamic therapy. Moreover, under laser irradiation, the heat garnered by the photothermal conversion of PB can be applied for photothermal therapy and enhance the generation of toxic ˙OH as well as the amount of DOX released, further boosting chemo- and chemodynamic therapy to realize a combined therapy. Importantly, the PB@Cu2+/ZnP NPs effectively limit the growth of tumors via the coordinated action of chemo/chemodynamic/photothermal therapy and no noticeable systematic toxicity can be found in mice. Taken together, the PB@Cu2+/ZnP NPs can act as a prospective therapeutic nanoplatform for multi-modal therapy of tumors.

[Effect of Wangbuliuxing combined with massage on breastfeeding and lactation function in cesarean section women].

OBJECTIVE: To explore the effect of Wangbuliuxing (semen vaccariae) combined with massage at breast and acupoint on breastfeeding and lactation function in cesarean section women. METHODS: A total of 120 cases of cesarean section women were randomly divided into an observation group and a control group, 60 cases in each group. The control group was treated with routine nursing. On the basis of the control group, the observation group was treated with oral administration of Wangbuliuxing decoction, twice a day for 7 days; in addition, massage at breast and acupoint (Zhongfu [LU 1], Yunmen [LU 2], Danzhong [CV 17], 2 min per acupoint per time) was given, twice a day for 7 days. The onset time of lactation, 48-hour postpartum lactation volume, breast swelling and pain, 42-day postpartum breastfeeding were compared between the two groups; the serum levels of prolactin at 48 and 72 h after delivery were measured, and the body mass of newborns at birth and 42 d after delivery were recorded. RESULTS: The onset time of lactation in the observation group was earlier than that in the control group (P<0.05), the 48-hour postpartum lactation volume was higher than the control group (P<0.05), and the breast swelling pain 48 h after delivery was lighter than the control group (P<0.05). Forty-two days after delivery, the success rate of breastfeeding in the observation group was 91.7% (55/60), which was higher than 76.7% (46/60) in the control group (P<0.05). At 48 and 72 h after delivery, the level of serum prolactin in the observation group was higher than that in the control group (P<0.05). On 42 d after delivery, the body mass of newborns in the two groups was higher than that at birth (P<0.05), and that in the observation group was higher than the control group (P<0.05). CONCLUSION: Wangbuliuxing combined with massage at acupoint and breast could significantly shorten the onset time of lactation, improve the lactation volume, effectively improve breast swelling and pain, increase breastfeeding rate and promote the growth and development of newborns.

Amphiphilic Janus nanoparticles for imaging-guided synergistic chemo-photothermal hepatocellular carcinoma therapy in the second near-infrared window.

Hepatocellular carcinoma (HCC) is one of the most common and deadly malignant tumors worldwide. With unsatisfactory effects of traditional systematic chemotherapy for HCC owing to its drug resistance, novel therapeutic strategies based on nanomaterials for HCC treatments are promising solutions. To solve the challenges of nanoparticles (NPs)-based drug delivery systems for potential clinical applications, we designed water soluble amphiphilic oleic acid-NaYF4:Yb,Er/polydopamine Au nanoflower Janus NPs (OA-UCNPs/PDA-AuF JNPs) with discrete multi compartment nanostructures as dual-drug delivery systems (DDDSs). This unique nanostructure meets the requirements for containing hydrophobic hydroxycamptothecin/hydrophilic doxorubicin in divided spaces and releasing each drug from non-interfering channels under pH/near-infrared (NIR) dual-stimuli. The amphiphilic DDDSs were utilized to eradicate the tumor burden on a high-fidelity HCC model of a patient-derived xenograft (PDX), and represented an efficient strategy for defeating HCC using multi-modal imaging-guided dual-drug chemo-photothermal therapy in the second NIR window. In addition, the potential mechanisms of action for the DDDSs were evaluated.

Selective Growth Synthesis of Ternary Janus Nanoparticles for Imaging-Guided Synergistic Chemo- and Photothermal Therapy in the Second NIR Window.

Multifunctional therapeutic agents in the second near-infrared (NIR-II) window have attracted wide attention on account of their synergetic properties for effective cancer therapy. Here, we construct a selective growth strategy for the first time to fabricate ternary Janus nanoparticles (JNPs) containing hemispherical MnO2 at one side and Au core covered with CuS shell at opposite side. The obtained ternary JNPs are further modified with poly(ethylene glycol)thiol to enhance the stability and biocompatibility (designated as PEG-CuS-Au-MnO2 ternary JNPs). The MnO2 domain with mesoporous structures can serve as hydrophobic drug carriers and magnetic resonance (MR) imaging contrast agents. Meanwhile, the Au segment is used for X-ray computed tomography (CT) imaging. Moreover, the PEG-CuS-Au-MnO2 ternary JNPs can conduct hyperthermia at 1064 nm in NIR-II window to ablate tumors in deep tissue, which is ascribed to the localized surface plasmon resonance coupling effect of the Au core and CuS domain. All of the results reveal that PEG-CuS-Au-MnO2 ternary JNPs not only exhibit pre-eminent CT/MR imaging capabilities, but also provide high chemo-photothermal antitumor efficacy under the guidance of CT/MR imaging. Taking together, the PEG-CuS-Au-MnO2 ternary JNPs can be regarded as a prospective therapeutic nanoplatform for dual-modal imaging-guided synergistic chemo-photothermal cancer therapy in the NIR-II window.

Rational Design of Branched Au-Fe3 O4 Janus Nanoparticles for Simultaneous Trimodal Imaging and Photothermal Therapy of Cancer Cells.

We report a facile and simple hydrogen reduction method to fabricate PEGylated branched gold (Au)-iron oxide (Fe3 O4 ) Janus nanoparticles (JNPs). Note that the hydrogen induces the formation of Fe3 O4 during the synthesis process. Due to the strong absorption in the near-infrared range, branched Au-Fe3 O4 JNPs showed a significant photothermal effect with a 40 % calculated photothermal transduction efficiency under a laser irradiation of 808 nm in vitro. Owing to their excellent optical and magnetic properties, branched Au-Fe3 O4 JNPs were demonstrated to be advantageous agents for triple-modal magnetic resonance imaging (MRI)/photoacoustic imaging (PAI)/computed tomography (CT) in vitro. Therefore, the synthetic approach could be extended to prepare Au-metallic oxide JNPs for specific applications.

Designed Synthesis of Au/Fe3 O4 @C Janus Nanoparticles for Dual-Modal Imaging and Actively Targeted Chemo-Photothermal Synergistic Therapy of Cancer Cells.

Elaborately designed novel multifunctional Janus nanoparticles (JNPs) have attracted considerable attention owing to their anisotropic surface properties and various functionalities that allow them to house several components for the detection and targeting of cancer cells. In this work, we report a novel and facile approach to synthesize Au/Fe3 O4 @C JNPs, which were further selectively functionalized with amino-poly(ethylene glycol)thiol (NH2 -PEG-SH) and folic acid (FA) on the exposed Au domains to achieve high contrast for X-ray computed tomography (CT) imaging, excellent stability, good biocompatibility, as well as cancer cell-specific targeting. Meanwhile, the other Fe3 O4 @C sides with mesoporous structure served as a drug delivery vehicle for doxorubicin (DOX), an efficient photothermal therapy (PTT) agent, and a magnetic resonance (MR) imaging contrast agent. Taking these features together, these unique multifunctional JNPs provide an intriguing nanoplatform for dual-modal CT and MR imaging-guided actively targeted chemo-photothermal synergistic cancer therapy.

Membrane insertion of αA-crystallin is oligomer-size dependent.

Vertebrate lens is one of the tissues with the highest soluble protein concentration. The predominant soluble proteins in lens fiber cells are crystallins, and among them, α-crystallins belong to the small heat shock protein family with chaperone-like activity. Although α-crystallins are highly soluble in waters, α-crystallins have been detected in the membrane-bound fraction of lens, which will increase in the aged or cataractous lens. In this research, we found αA-crystallin exhibited a complex thermal transition with remarkable changes in secondary and quaternary structures. Treatment of αA-crystallin at high temperatures induced larger oliogomers with higher hydrophobic exposure. Both heat-treated and untreated αA-crystallin could insert into lipid monolayer directly as revealed by monolayer surface pressure experiments. Heat-treatment facilitated the membrane insertion of αA-crystallin and increased the membrane-bound fraction in the cells. The membrane-binding ability of αA-crystallin could be altered by cataract-causing mutations R116C, R116H and Y118D. Our results suggested that the irreversible changes in oligomer size induced by various stresses might promote the membrane association of αA-crystallin and therefore might play a role in aged cataract. Alternations in the membrane binding ability of α-crystallins might be important to the understanding of both aged and congenital cataracts.

Nao-Xue-Shu Oral Liquid Improves Aphasia of Mixed Stroke.

Objective. The objective is to observe whether the traditional Chinese medicine (TCM) Nao-Xue-Shu oral liquid improves aphasia of mixed stroke. Methods. A total of 102 patients with aphasia of mixed stroke were divided into two groups by a single blind random method. The patients treated by standard Western medicine plus Nao-Xue-Shu oral liquid (n = 58) were assigned to the treatment group while the remaining patients treated only by standard Western medicine (n = 58) constituted the control group. Changes in the Western Aphasia Battery (WAB), Modified Rankin Scale (mRS), National Institutes of Health Stroke Scale (NIHSS), and hemorheology parameters were assessed to evaluate the effects of the treatments. Results. Excluding the patients who dropped out, 54 patients in the treatment group and 51 patients in the control group were used to evaluate the effects. Significant and persistent improvements in the WAB score, specifically comprehension, repetition, naming, and calculating, were found in the treatment group when the effects were evaluated at the end of week 2 and week 4, respectively, compared with baseline. The naming and writing scores were also improved at the end of week 4 in this group. The comprehension and reading scores were improved at the end of week 4 in the control group compared with the baseline, but the improvements were smaller than those in the treatment group. The percentages of patients at the 0-1 range of mRS were increased at the end of week 2 and week 4 in both groups, but the improvements in the treatment group were much larger than those in the control group. Greater improvements in the NIHSS scores and the hemorheology parameters in the treatment group were also observed compared with the control group at the end of week 2 and week 4. Conclusion. Nao-Xue-Shu oral liquid formulation improved aphasia in mixed stroke patients and thus might be a potentially effective drug for treating stroke aphasia.

[Analysis on allergen of clinical allergic rhinitis patients in north-west mountain area of Hubei Province].

OBJECTIVE: To investigate the main inhaled allergens and the difference of that between city and rural suburbs in patients with allergic rhinitis in the mountain region of the northwest Hubei province and to provide epidemiological basis for prevention and treatment in the region. METHOD: Eight hundred and thirty-five cases who were diagnosed as allergic rhinitis with standardized allergens in Taihe Hospital of Hubei University of Medicine from Sep 2009 and Dec 2011 were studied. The data of allergens and the distribution of the patients were recorded and analyzed. χ2-test were used to analyze the data. RESULT: The top 7 of inhaled allergens were house dust mites (89.6%), dust mites (86.0%), tropical mites (56.9%), croton bug (18.8%), felon herb (8.1%), the cat hair (8.1%) and fine chain alternata bacteria (9.5%), Two main kinds of allergen in three different area are with no obvious difference (P > 0.05). CONCLUSION: In northwest Hubei Province, the highest rate of inhaled allergens was dust mites, which are approximate in different age groups and different regions, especially in the city.

The use of integrative therapies in patients with amyotrophic lateral sclerosis in shanghai, china.

Objective. To investigate the current use of integrative therapies (IT) in the treatment of patients with amyotrophic lateral sclerosis (ALS). Methods. A cross-sectional, multicenter clinical epidemiological survey was conducted in 12 hospitals in Shanghai. We investigated the type and frequency of IT use and determined whether the use of IT correlated with demographic, social, or disease-specific characteristics in our patient population. Results. A total of 231 (89.5%) of 258 patients with ALS were eligible for the study and 229 (99% of all) of 231 reported the use of at least one IT for the treatment of ALS. Vitamins and Chinese herb decoctions, Chinese herb compounds, massage therapy, and acupuncture were the 5 most commonly used therapies. There was a strong association between education level, income, and use of IT. A household income of more than 75,000 RMB ($49,995) correlated with multiple IT use, and married patients used IT more often than single individuals. The main reasons for using IT were to treat weakness and fatigue, muscle atrophy, the development of ALS, depression, insomnia, limb pain or numbness, and side effects associated with Riluzole. Conclusion. The use of IT is common in patients with ALS in Shanghai. Vitamins and TCM are the most used additional therapies and the widespread and largely unexamined use of IT for ALS requires more attention.

Osthole improves acute lung injury in mice by up-regulating Nrf-2/thioredoxin 1.

Inhibiting reactive oxygen species (ROS) has been viewed as a therapeutic target for the treatment of acute lung injury (ALI). Osthole, an active component in Chinese herbal medicine, has drawn increasing attention because of its various pharmacological functions, including anti-inflammatory and anti-oxidative activities. The aim of the present study was to examine the effects of osthole on ALI induced by lipopolysaccharide (LPS) through intratracheal instillation. The mRNA and protein expression levels of thioredoxin 1 (Trx1) and the nuclear factor erythroid-2 related factor 2 (Nrf2) were detected by real-time PCR, reverse transcription PCR (RT-PCR) and Western blot, respectively. ROS production was measured by flow cytometry. Our results showed that osthole treatment improved the mice survival rates in the middle and high dosage groups, compared with the untreated LPS group. Moreover, osthole treatment significantly improved LPS-induced lung pathological damage, and it decreased the lung injury scores, lung wet/dry ratios and the total protein level in Bronchoalveolar lavage fluid (BALF). Osthole treatment dramatically reduced the H2O2, MDA and OH levels in the lung homogenates. LDH and ROS were markedly reduced in the osthole+LPS group in vitro. Furthermore, osthole increased Nrf2 and Trx1 expression in terms of mRNA and protein in vivo and in vitro. Nrf2 siRNA (siNrf2) could suppress the beneficial effects of osthole on ALI. In conclusion, the current study demonstrates that osthole exerted protective effects on LPS-induced ALI by up-regulating the Nrf-2/Trx-1 pathway.