Isolation, structure modification, and anti-rheumatoid arthritis activity of isopimarane-type diterpenoids from Orthosiphon aristatus.

Orthosiphon aristatus is a well-known folkloric medicine and herb for Guangdong soup for the treatment of rheumatism in China. Eight isopimarane-type and migrated pimarane-type diterpenoids (1-8), including a new one with a rarely occurring α,ß-unsaturated diketone C-ring, were isolated from O. aristatus. Their structures were determined by spectroscopic methods and quantum chemical calculations. Furthermore, the most abundant compound, orthosiphol K, was structurally modified by modern synthetic techniques to give seven new derivatives (9-15). The anti-rheumatoid arthritis activity of these diterpenoids were evaluated on a TNF-α induced MH7A human rheumatoid fibroblast-like synoviocyte model. Compound 10 showed the most potent activity among these compounds. Based on their inhibitory effects on the release levels of IL-1ß, the preliminary structure-activity relationships were concluded. Furthermore, western blot analysis revealed that 10 could increase the expression of IκBα and decrease the expression of NF-κB p65, and the expression levels of COX-2 and NLRP3 proteins were consequently down-regulated.

Efficacy and safety of the modified Zhiwang decoction combined with methotrexate in early rheumatoid arthritis: study protocol for a randomised controlled trial.

INTRODUCTION: Rheumatoid arthritis (RA) is a progressive inflammatory autoimmune disease characterised by chronic systemic inflammation, which can cause swelling, stiffening and destruction of articular cartilage and bone. Early diagnosis and treatment of RA can improve outcomes and slow the progression of joint damage. Preliminary exploratory research had hinted an expected effect of modified Zhiwang decoction (MZWD) in treating early RA. However, few randomised clinical trials have evaluated the effectiveness of MZWD in early RA. Therefore, a parallel-group randomised controlled trial was designed to evaluate the efficacy and safety of MZWD combined with methotrexate (MTX) on early RA. METHODS AND ANALYSIS: This is a prospective, parallel-group, single-centre randomised controlled clinical study. A total of 150 patients will be randomly assigned to either the treatment (n=75) or control group (n=75). The treatment group will receive MZWD and MTX, and the control group will receive MTX for 12 weeks. The primary outcome of this study is Disease Activity Score-28, and the secondary outcomes are Fatigue Scale-14, Visual Analogue Scale pain scores and traditional Chinese medicine symptom scores. Safety outcomes, including adverse events and results of ECG and laboratory tests, will be monitored. ETHICS AND DISSEMINATION: Ethics approval was obtained from the Clinical Research Ethics Committee of the China-Japan Friendship Hospital (no. 2022-KY-124) on 8 July 2022. The findings will be disseminated in peer-reviewed publications. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov Registry (NCT05508815).

Eosinophilic fasciitis difficult to differentiate from scleroderma: A case report.

BACKGROUND: Eosinophilic fasciitis (EF) is a rare connective tissue disease that can cause swelling and sclerosis of the extremities, and special attention is needed to differentiate EF from systemic sclerosis. Misdiagnosis or omission markedly delays treatment of EF, and severe skin sclerosis in advanced stages can cause joint contracture and tendon retraction, worsening the patient's prognosis and quality of life. CASE SUMMARY: We report a case of EF in a young woman diagnosed by tissue biopsy, confirming the difficulty of differential diagnosis with scleroderma. CONCLUSION: Focusing on skin manifestations, completing tissue biopsy and radiography can help diagnose EF effectively. Clinicians should enhance their understanding of the differences between EF and scleroderma, and early diagnosis and standardized treatment can improve the prognosis of patients with EF.

Gene mutations in the PI3K/Akt signaling pathway were related to immune thrombocytopenia pathogenesis.

BACKGROUND: Immune thrombocytopenic (ITP) is an autoimmune bleeding disease with genetic susceptibility. Twenty newly diagnosed active primary ITP patients who had not been treated with glucocorticosteroids, immune globulin or immunosuppressants prior to sampling were enrolled in this study. Bone marrow blood mononuclear cells were used for whole exome sequencing to further elucidation the variant genes of ITP. METHODS: High-molecular-weight genomic DNA was extracted from freshly frozen bone marrow blood mononuclear cells from 20 active ITP patients. Next, the samples were subjected to molecular genetic analysis by whole-exome sequencing, and the results were confirmed by Sanger sequencing. The signaling pathways and cellular processes associated with the mutated genes were identified with gene ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses. RESULTS: The results showed that there were 3998 missense mutations involving 2269 genes in more than 10 individuals. Unique genetic variants including phosphatase and tensin homolog, insulin receptor, and coagulation factor C homology were the most associated with the pathogenesis of ITP. Functional analysis revealed these mutation genes mainly affect Phosphatidylinositol 3 kinase/serine/threonine kinase B signaling pathways (signal transduction) and platelet activation (immune system). CONCLUSION: Our finding further demonstrates the functional connections between these variant genes and ITP. Although the substantial mechanism and the impact of genetic variation are required further investigation, the application of next generation sequencing in ITP in this paper is a valuable method to reveal the genetic susceptibility.

[Response of Topsoil Fungal Community Structure to Soil Improvement Measures in Degraded Forest of Red Soil Region].

Soil fungal community structure and diversity are highly sensitive to variations in the external environment, as well as soil improvement measures. In order to clarify the effects of soil improvement measures on topsoil fertility or quality, a field experiment was conducted in eroded forest of a red soil region. Organic fertilizer, biochar, and lime+microbial fertilizer were added to the topsoil, respectively. After four years, the chemistry properties and nutrients in the topsoil were measured, and the diversity and composition of fungi were analyzed. The results showed that the additions of organic fertilizer, biochar, and lime+microbial fertilizer reduced fungal richness in topsoil, compared to that with no fertilizer addition (CK). Among them, lime+microbial fertilizer had the most negative effect on fungal richness. The three soil improvement measures also affected the diversity of topsoil fungi, but the impacts were not significant. The dominant fungal phyla in the topsoil were Ascomycota (31.29%-46.55%) and Basidiomycota (30.07%-70.71%), and the dominant fungal genera were Amphinema and Archaeorhizomyces. The effects of soil improvement measures on fungal community structure in the topsoil were different; organic fertilizer increased the relative abundance of Ascomycetes and Archaeopteroides, and biochar enhanced the relative abundance of Basidiomycetes and Archaeopteroides, whereas lime+microbial fertilizer improved the relative abundance of Basidiomycetes and Archaeopteroides. Fungal diversity and community structure in the topsoil was affected by edaphic factors, and fungal richness was regulated by pH value, whereas fungal community structure was influenced by pH, total nitrogen, and organic carbon. This study provides scientific guidance for soil improvement and ecological restoration below the canopy in eroded forests of red soil regions.

Epimedii Herba: An ancient Chinese herbal medicine in the prevention and treatment of rheumatoid arthritis.

Rheumatoid arthritis (RA) is a chronic, progressive inflammatory and systemic autoimmune disease resulting in severe joint destruction, lifelong suffering and considerable disability. Diverse prescriptions of traditional Chinese medicine (TCM) containing Epimedii Herba (EH) achieve greatly curative effects against RA. The present review aims to systemically summarize the therapeutic effect, pharmacological mechanism, bioavailability and safety assessment of EH to provide a novel insight for subsequent studies. The search terms included were "Epimedii Herba", "yinyanghuo", "arthritis, rheumatoid" and "Rheumatoid Arthritis", and relevant literatures were collected on the database such as Google Scholar, Pubmed, Web of Science and CNKI. In this review, 15 compounds from EH for the treatment of RA were summarized from the aspects of anti-inflammatory, immunoregulatory, cartilage and bone protective, antiangiogenic and antioxidant activities. Although EH has been frequently used to treat RA in clinical practice, studies on mechanisms of these activities are still scarce. Various compounds of EH have the multifunctional traits in the treatment of RA, so EH may be a great complementary medicine option and it is necessary to pay more attention to further research and development.

Leucine-rich repeat kinase 2 is protective during acute kidney injury through its activation of autophagy in podocytes.

Leucine-rich repeat kinase 2 (LRRK2) is a known regulator of autophagy in a range of cell types. Here, we investigated the role of LRRK2-associated autophagy during acute kidney injury (AKI) and its underlying mechanism(s) of action. Male mice aged 8-weeks were treated with the LRRK2 inhibitor MLi-2 and exposed to lipopolysaccharide (LPS) through intraperitoneal injection or ischemia-reperfusion (IR) surgery. Mice were sacrificed 12 or 24 h post-LPS injection or IR operation and blood was collected for serum creatinine measurements. Kidney cortical tissues were collected for western blot analysis of podocyte-specific markers and autophagy-associated proteins. Renal histopathology was observed through hematoxylin-eosin staining. For cell-based assays, immortalized mouse podocytes were silenced for LRRK2 through siRNA transfection and exposed to LPS or cobalt chloride. Changes in cell viability were investigated using cell counting kit-8, flow cytometry and MTT assays. Expression of podocyte-specific markers and autophagy-associated proteins were analyzed by western blotting. We observed an increase in LRRK2 expression at 12 h post-LPS injection and IR surgery that was accompanied by enhanced autophagy. At 24 h post-treatment, both LRRK2 expression and autophagy declined. Kidney injury was most pronounced in mice treated with MLi-2. Podocytes silenced for LRRK2 showed a loss of cell viability, decreased levels of podocyte-specific protein expression and a suppression of autophagy. Together, these data reveal the protective effects of LRRK2 during AKI through enhanced podocyte autophagy and cell viability.

Construction of azaheterocycles via Pd-catalyzed migratory cycloannulation reaction of unactivated alkenes.

Azahetereocycles constitute important structural components in many biologically active natural compounds and marketed drugs, and represent the most promising scaffolds in drug discovery. Accordingly, the development of efficient and general synthetic methods for the construction of diverse azaheterocycles is the major goal in synthetic chemistry. Herein, we report the efficient construction of a wide range of azaheterocycles via a Pd-catalyzed migratory cycloannulation strategy with unactivated alkenes. This strategy enables the rapid synthesis of a series of 6-, 7- and 8-membered azaheterocycles in high efficiency, and features a broad substrate scope, excellent functional group tolerance under redox-neutral conditions. The significance of this finding is demonstrated by the efficient synthesis of drug-like molecules with high step-economy. Preliminary mechanistic investigations reveal that this reaction underwent a sequentially migratory insertion to alkenes, metal migration process, and the aza-Michael addition to a quinone methide intermediate.

Design and synthesis of ludartin derivatives as potential anticancer agents against hepatocellular carcinoma.

Our previous study demonstrated that guaiane-type sesquiterpenoid ludartin showed potent antihepatoma activity against two human hepatocellular carcinoma cell lines, HepG2 and Huh7, with IC50 values of 32.7 and 34.3 µM, respectively. In this study, 34 ludartin derivatives were designed, synthesized and evaluated for their cytotoxic activities against HepG2 and Huh7 cell lines using an MTT assay in vitro. As a result, 17 compounds increased the activity against HepG2 cells, and 20 compounds enhanced the activity against Huh7 cells; 14 derivatives 2, 4-7, 9, 11, 17, 24, 28-30 and 32-33 were superior to ludartin on both HepG2 and Huh7 cells. In particular, dimeric derivative 33 as the most active compound showed 20-fold and 17-fold enhancement of cytotoxicity against HepG2 and Huh7 cells compared to that of ludartin. These results suggested that compound 33 could serve as a promising lead compound against liver cancer. Graphical abstract.

Genetic and Pathogenic Characterisation of a Virulent Akabane Virus Isolated from Goats in Yunnan, China.

Introduction: Akabane virus (AKAV) has been detected in a variety of host species in China, but there are only limited records of its occurrence in goats. However, more attention needs to be paid to understanding the diversity of viruses in this species. The aim of the study was to explore the genotype characteristics and variation trend of AKAV and their relationship with virulence in Yunnan, China. Material and Methods: Blood samples were collected from goats during routine surveillance of goat diseases in Yunnan province in 2019. The AKAV CX-01 strain was isolated using BHK-21 cells. To understand pathogenicity, the virus was intraperitoneally (IP) and intracerebrally (IC) inoculated into suckling mice and tissue samples were subsequently analysed histopathologically and immunohistochemically. Results: Akabane virus CX-01 strain induced encephalitis and impairment of the central nervous system with fatal consequences. Phylogenetic analysis based on the ORF sequences of the small segments indicated that the AKAV isolate used was most closely related to the GD18134/2018 Chinese midge and bovine NM BS/1strains, while phylogenetic analysis based on the medium segments showed a close relationship between CX-01 and the Chinese GLXCH01 strain. Conclusion: The CX-01 isolate was related to AKAV genogroup Ia and probably originated from a recombination of different strains.

[Effects of exogenous methylglyoxal on chesnut seedlings under drought stress]. / å¤–æºç”²åŸºä¹™äºŒé†›å¯¹å¹²æ—±èƒè¿«ä¸‹æ¿æ —å¹¼è‹—çš„å½±å“.

Methylglyoxal (MG) is a novel signaling molecule with multiple functions in plants. To explore the effects of MG on Chinese chestnut (Castanea mollissima) under drought stress, two-year-old 'Huangpeng' chestnut seedlings were treated with 15% polyethylene glycol (PEG) coupled with MG or its scavenger N-acetyl-L-cys-teine (NAC). We measured the activities of antioxidant enzymes, including superoxide dismutase (SOD), peroxidase (POD), catalase (CAT), ascorbate peroxidase (APX) and glutathione reductase (GR), and glyoxalase enzymes, including glyoxalase Ⅰ (GlyⅠ) and glyoxalase Ⅱ(GlyⅡ). Contents of antioxidants such as endogenous MG, malondialdehyde (MDA), H2O2, and O2-· as well as the osmotic adjustment substances including proline (Pro), soluble sugar (SS), glycine betaine (GB) were also detected. The results showed that 0.5 mmol·L-1 MG significantly increased the activities of antioxidant enzymes (SOD, POD, CAT, APX, GR) and glyoxalase enzymes (GlyⅠ, GlyⅡ) in leaves of chestnut seedlings under drought stress, elevated the contents of osmotic adjustment substances (Pro, SS, GB) and antioxidant substances (ASA, GSH), and reduced the contents of MG, MDA, H2O2, O2-· and dehydroascorbate (DHA). Drought stress induced damages such as membrane lipid peroxidation and osmotic stress was alleviated by MG, leading to an overall improved adaptability of chestnut to drought stress. Moreover, the addition of MG scavenger NAC could reverse the effects induced by MG, indicating that MG had positive impacts on drought resistance of chestnut plants. Our study provided a theoretical basis for further exploring the mechanism of MG in alleviating drought stress induced symptoms in chestnut.

Biomimetic Synthesis of Lavandiolides H, I, and K and Artematrolide F via Diels-Alder Reaction.

The biomimetic synthesis of guaianolide dimers lavandiolides H, I, and K and artematrolide F containing a spirolactone moiety has been accomplished for the first time from naturally abundant arglabin in four to six steps with an overall yield up to 60%, and a series of natural product-like guaianolide dimers, trimer, and tetramer were also successfully synthesized. Notably, the trimeric compound exhibited antihepatoma cytotoxicity more potent than that of sorafenib with IC50 values of 6.2 µM (HepG2), 6.8 µM (Huh7), and 7.2 µM (SK-HEP-1).

circRNA hsa_circ_0005909 Predicts Poor Prognosis and Promotes the Growth, Metastasis, and Drug Resistance of Non-Small-Cell Lung Cancer via the miRNA-338-3p/SOX4 Pathway.

BACKGROUND: Circular RNAs (circRNAs) are powerful factors in regulating various cancer behaviors. It has been manifested in previous researches that circular RNA hsa_circ_0005909 (circ_0005909) exhibits a regulatory function in osteosarcoma. However, there are no other studies on whether circ_0005909 displays potential functions on the progression of non-small-cell lung cancer (NSCLC). METHODS: RT-PCR was applied to examine the expression of circ_0005909 in NSCLC. To study the specific behaviors of NSCLC cells after circ_0005909 knockdown, cell counting kit-8 (CCK-8) assays, colony formation assays, Transwell assays, and xenograft tumor model assays were conducted. Bioinformatics and luciferase reporter assays were employed to study the association among circ_0005909, miRNA-338-3p, and SOX4. RESULTS: In this research, our group firstly showed that circ_0005909 expressions were distinctly increased in NSCLC specimens and cell lines. Clinical studies revealed that high circ_0005909 expressions were associated with poor prognosis of NSCLC patients. Functionally, knockdown of circ_0005909 was observed to suppress the proliferation, metastasis, and drug resistance of NSCLC cells. In the terms of mechanism, circ_0005909 could act as a sponge of miRNA-338-3p, and miRNA-338-3p could target SOX4. In addition, miRNA-338-3p inhibitors reversed the suppressor ability of circ_0005909 silence on NSCLC behaviors. CONCLUSIONS: circ_0005909 promoted the progression of NSCLC via the modulation of the miRNA-338-3p/SOX4 axis, which may be a therapeutic target for NSCLC.

Synthesis and anti-fibrotic effects of santamarin derivatives as cytotoxic agents against hepatic stellate cell line LX2.

Liver fibrosis is a final result of extensive deposition of extracellular matrix (ECM) and starts with the activation and proliferation of hepatic stellate cells (HSCs). Our previous study showed that eudesmane sesquiterpenoid santamarin had cytotoxicity against hepatic stellate cell line LX2 (HSC-LX2) with IC50 values of 16.5 ± 0.7 µM. To explore the structure-activity relationships, twenty-six derivatives were synthesized by modifying the hydroxyl group, double-bond and unsaturated lactone. Cytotoxicity evaluation suggested that eight derivatives (6, 9, 13, 17, 20 and 25-27) increased activity against HSC-LX2. Especially, derivatives 17, 20 and 25 displayed obvious cytotoxicity with IC50 values of 6.4 ± 0.4, 4.6 ± 0.1, and 3.5 ± 0.1 µM, which were 3 to 5-fold higher than santamarin. Preliminary mechanisms study revealed that the active compound 20 exhibited more than 8-fold and 6-fold enhancement of inhibitory effect on the deposition of human hyaluronic acid (HA) and human laminin (HL) with IC50 values of 7.6 ± 0.6 and 3.3 ± 1.2 µM.

Cytotoxic sesquiterpenoids against hepatic stellate cell line LX2 from Artemisia lavandulaefolia.

The preliminary assay suggested that the EtOH extract of Artemisia lavandulaefolia had cytotoxicity against hepatic stellate cell line LX2 (HSC-LX2) with an inhibitory ratio of 94.1% at 400 µg/mL. Bioassay-guided investigation led to eleven new sesquiterpenoids, artemilavanolides C-F (1-4) and artemlavandulolides A-G (5-11), as well as thirteen known compounds (12-24). Their structures were elucidated by extensive spectroscopic data and X-ray crystallographic analysis. Cytotoxicity evaluation suggested that fourteen compounds exhibited activity against HSC-LX2; compounds 22, 23 and 24 were comparable to the positive control, silybin (IC50, 162.3 µM); compounds 6, 9 and 16 showed moderate activity with IC50 values of 109.3, 114.0 and 124.2 µM. Importantly, compounds 14, 15 and 18 displayed significant cytotoxicity against HSC-LX2 with IC50 values of 52.1, 16.5 and 21.3 µM, and inhibitory activity on the deposition of human collagen type I (Col I) and human laminin (HL) with IC50 values ranging from 7.3 to 71.6 µM and from 18.6 to 72.9 µM.

Transcriptome analysis of activated charcoal-induced growth promotion of wheat seedlings in tissue culture.

BACKGROUND: Activated charcoal (AC) is highly adsorbent and is often used to promote seedling growth in plant tissue culture; however, the underlying molecular mechanism remains unclear. In this study, root and leaf tissues of 10-day-old seedlings grown via immature embryo culture in the presence or absence of AC in the culture medium were subjected to global transcriptome analysis by RNA sequencing to provide insights into the effects of AC on seedling growth. RESULTS: In total, we identified 18,555 differentially expressed genes (DEGs). Of these, 11,182 were detected in the roots and 7373 in the leaves. In seedlings grown in the presence of AC, 9460 DEGs were upregulated and 7483 DEGs were downregulated in the presence of AC as compared to the control. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis revealed 254 DEG-enriched pathways, 226 of which were common between roots and leaves. Further analysis of the major metabolic pathways revealed that AC stimulated the expression of nine genes in the phenylpropanoid biosynthesis pathway, including PLA, CYP73A, COMT, CYP84A, and 4CL, the protein products of which promote cell differentiation and seedling growth. Further, AC upregulated genes involved in plant hormone signaling related to stress resistance and disease resistance, including EIN3, BZR1, JAR1, JAZ, and PR1, and downregulated genes related to plant growth inhibition, including BKI1, ARR-B, DELLA, and ABF. CONCLUSIONS: Growth medium containing AC promotes seedling growth by increasing the expression of certain genes in the phenylpropanoid biosynthesis pathway, which are related to cell differentiation and seedling growth, as well as genes involved in plant hormone signaling, which is related to resistance.

Facile Preparation of Highly Stretchable TPU/Ag Nanowire Strain Sensor with Spring-Like Configuration.

Stretchable nano-fibers have attracted dramatic attention for the utility in wearable and flexible electronics. In the present case, Ag nanowires (AgNWs)-intertwined thermoplastic polyurethanes (TPU) unwoven nano-membrane is fabricated by an electrospinning method and dip coating technique. Then a strain sensor with a spring-like configuration is fabricated by a twisted method. The sensor exhibits superior electrical conductivity up to 3990 S cm-1 due to the high weight percentage of the Ag nanowires. Additionally, thanks to the free-standing spring-like configuration that consists of uniform neat loops, the strain sensor can detect a superior strain up to 900% at the point the sensor ruptures. On the other hand, the configuration can mostly protect the AgNWs from falling off. Furthermore, major human motion detection, like movement of a human forefinger, and minor human motion detection, such as a wrist pulse, show the possible application of the sensor in the field of flexible electronics.

Poor preoperative sleep quality is a risk factor for severe postoperative pain after breast cancer surgery: A prospective cohort study.

The aim of this study was to assess the effect of preoperative sleep quality on acute postoperative pain in breast cancer patients.The Pittsburgh Sleep Quality Index questionnaire (PSQI) was used to assess the overall sleep status of women scheduled for unilateral modified radical mastectomy in the past month. Based on the responses, patients were allocated to good sleep group or poor sleep group. Postoperatively, acute pain was assessed using the numerical rating score in the first 24 hours; in addition, the requirement of analgesics and the incidence of postoperative complications were recorded.A total of 108 breast surgery patients were enrolled. Based on the PSQI results, 55 (51%) patients were allocated to poor sleep group and 53 (49%) to good sleep group. Pain scores were similar in the 2 groups at the end of surgery (P = .589); however, poor sleep group reported higher postoperative pain scores than the good sleep group at 2 (P = .002), 6 (P < .001), 12 (P < .001), and 24 (P = .002) hours after surgery. The incidence of severe pain in the poor sleep group was higher than that in the good sleep group (27% vs 8%, P = .018), and the ratio of participants who required rescued analgesics was greater in the poor sleep group (52% vs 22%, P = .002). In addition, patients with poor sleep quality had more postoperative complications and longer hospital stay.In this study, breast cancer patients with poor preoperative sleep quality reported more severe postoperative pain, required more analgesics, experienced more complications, and had longer hospital stay.

Paclitaxel-loaded nanobubble targeted to pro-gastrin-releasing peptide inhibits the growth of small cell lung cancer.

OBJECTIVE: The aim of this work was to study the effects of paclitaxel-loaded nanobubbles targeting pro-gastrin-releasing peptide, designated as paclitaxel targeting nanobubbles, on small cell lung cancer (SCLC). METHODS: Paclitaxel targeting nanobubbles were prepared by Thin-film hydration method. Subsequently, the prepared nanomaterials were tested for their in vitro effects on SCLC H446 cells proliferation, apoptosis and motility using the CCK-8 assay, flow cytometry and cell scratch test. Next, the potential molecular regulatory mechanisms of the prepared nanomaterials on H446 cells were evaluated by RT-PCR, Western blot and immunohistochemical detection. Finally, the in vivo effects of the constructed nanomaterials were assessed on SCLC tumor using tumor-burdened nude mice models. RESULTS: Paclitaxel targeting nanobubbles significantly inhibited SCLC cell proliferation and migration, and promoted cell apoptosis. Moreover, the expression levels of Bcl-2, survivin, CDK2 and MMP-2 significantly decreased in SCLC cells treated with paclitaxel targeting nanobubbles, whereas the expression of caspase-3 and Rb were increased. There was a notable decrease in tumor size in vivo in SCLC nude mice models treated with paclitaxel targeting nanobubbles. CONCLUSION: Paclitaxel targeting nanobubbles effectively inhibited the proliferation, migration and invasion of SCLC cells and induced SCLC cells apoptosis. Hence, these nanobubbles show potential in SCLC-targeted drug treatment application.

Clinical Efficacy and Safety of Bathing with Chinese Medicine Taohong Siwu Decoction () for Treatment of Diffuse Cutaneous Systemic Sclerosis: A Randomized Placebo-Controlled Trial.

OBJECTIVE: To examine the efficacy and safety of bathing therapy with Taohong Siwu Decoction (, TSD) in the treatment of early-stage, mild-moderate diffuse cutaneous systemic sclerosis (dcSSc). METHODS: This randomized, placebo-controlled trial enrolled 148 men and women (18-60 years) with dcSSc (disease duration 12 months) and baseline modified Rodnan skin score (MRSS) 10. Patients were randomized into a TSD group (71 cases bathing with TSD plus oral prednisone) or control group (71 cases bathing with placebo plus oral prednisone). Bathing (40 °C, 30 min) of the upper and lower limbs was carried out once daily for 12 consecutive weeks. The primary outcome measure was MRSS; secondary outcomes were Raynaud's phenomenon (RP) score, quality of life (QOL), physician visual analogue scale (VAS), patient VAS, percent predicted diffusing capacity for carbon monoxide (DLCO), percent predicted forced vital capacity (FVC), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) level and overall treatment effect. RESULTS: The final analysis included 135 patients (control group, 68 cases; TSD group, 67 cases). Primary and secondary outcome measures after 2 weeks of treatment showed no improvement (versus baseline) in both groups, with no differences between groups. At 12 weeks, QOL, physician VAS, patient VAS, ESR and CRP were improved in both groups, but MRSS and RP score were improved only in the TSD group (all P<0.05). MRSS, RP score, QOL, physician VAS, patient VAS, ESR and CRP differed significantly between groups (all P<0.05). Meanwhile, the overall treatment effect was significantly higher in the TSD group than in the control group (P<0.05). Adverse events in the two groups were similar (P>0.05). CONCLUSIONS: Bathing with TSD plus oral prednisone achieves better outcomes than oral prednisone alone in patients with dcSSc and is not associated with serious adverse events.