Antibacterial and Anti-Inflammatory Polysaccharide from Fructus Ligustri Lucidi Incorporated in PVA/Pectin Hydrogels Accelerate Wound Healing.

In cutaneous wound healing, an overproduction of inflammatory chemokines and bacterial infections impedes the process. Hydrogels can maintain a physiologically moist microenvironment, absorb chemokines, prevent bacterial infection, inhibit bacterial reproduction, and facilitate wound healing at a wound site. The development of hydrogels provides a novel treatment strategy for the entire wound repair process. Here, a series of Fructus Ligustri Lucidi polysaccharide extracts loaded with polyvinyl alcohol (PVA) and pectin hydrogels were successfully fabricated through the freeze-thaw method. A hydrogel containing a 1% mixing weight ratio of FLL-E (named PVA-P-FLL-E1) demonstrated excellent physicochemical properties such as swellability, water retention, degradability, porosity, 00drug release, transparency, and adhesive strength. Notably, this hydrogel exhibited minimal cytotoxicity. Moreover, the crosslinked hydrogel, PVA-P-FLL-E1, displayed multifunctional attributes, including significant antibacterial properties, earlier re-epithelialization, production of few inflammatory cells, the formation of collagen fibers, deposition of collagen I, and faster remodeling of the ECM. Consequently, the PVA-P-FLL-E1 hydrogel stands out as a promising wound dressing due to its superior formulation and enhanced healing effects in wound care.

Large Yellow Tea Polysaccharide Alleviates HFD-Induced Intestinal Homeostasis Dysbiosis via Modulating Gut Barrier Integrity, Immune Responses, and the Gut Microbiome.

Long-term high-fat diet (HFD) will induce dysbiosis and a disturbance of intestinal homeostasis. Large yellow tea polysaccharide (LYP) has been shown to improve obesity-associated metabolic disease via modulation of the M2 polarization. However, the contribution of LYP to intestinal barrier impairment and improvement mechanisms in obesity caused by an HFD are still not clear. In this study, we evaluated the impacts of LYP on the mucosal barrier function and microbiota composition in HFD-feeding mice. Results exhibited that dietary LYP supplement could ameliorate the physical barrier function via maintaining intestinal mucosal integrity and elevating tight-junction protein production, strengthen the chemical barrier function via up-regulating the levels of glucagon-like peptide-1 and increasing mucin-producing goblet cell numbers, and enhance the intestinal immune barrier function though suppressing immune cell subsets and cytokines toward pro-inflammatory phenotypes. Moreover, LYP reshaped the constitution and metabolism of intestinal flora by enriching probiotics that produce short-chain fatty acids. Overall, LYP might be used as a critical regulator of intestinal homeostasis to improve host health by promoting gut barrier integrity, modulating intestinal immune response, and inhibiting bowel inflammation.

Efficacy of Black Gold, Delicate Pulse Light, Super Photon Skin Rejuvenation for Pigmented Dermatoses.

Context: Pigmented dermatoses are skin diseases characterized by pigmentation changes in the skin's surface due to abnormal melanocyte production. Photon-skin-rejuvenation technology can be effective for the management of facial pigmented dermatoses. Black Gold Delicate Pulse Light (DPL) Super Photon Skin Rejuvenation therapy is a new technology based on traditional photo rejuvenation. Objective: The study intended to evaluate the therapeutic efficacy of DPL therapy in the management of targeted pigmented skin diseases, such as melasma, solar lentigines, and postinflammatory hyperpigmentation. Design: The research team conducted a prospective cohort study. Setting: The study took place at Department of Dermatology, Affiliated Hospital of Shaoxing University, Shaoxing, China. Participants: Participants were 130 patients with facial pigmented dermatoses treated at the hospital between February 2021 and December 2021. Interventions: The research team assigned participants to one of two groups, with 65 participants in each group: (1) the control group, the intense pulsed light (IPL) group, who received IPL treatment, and (2) the intervention group, the DPL group, who received black gold DPL super photon skin rejuvenation. Both groups received the treatments once a month for 6 months. Outcome Measures: At baseline and postintervention for both groups, the research team: (1) collected 5 ml of fasting venous blood from participants and measured serum concentrations of melatonin (MEL), vascular endothelial growth factor (VEGF) and endothelin-1 (ET-1) using enzyme-linked immunosorbent assay (ELISA); (2) assessed the degree of reduction of facial pigmentation using the Visia skin test and each participant's clinical results and calculated total efficacy; and (3) monitored and recorded adverse events. Results: Compared to the IPL group, the DPL group: (1) had greater symptom mitigation of the facial pigmented dermatosis, as evinced by significantly lower serum MEL (P = .001) and ET-1 (P = .020) concentrations and higher VEGF levels (P = .001); (2) for participants with freckles (P = .045), cafe-au-lait spots (P = .021), or post-acne hyperpigmentation (P = .029), had a significantly higher total efficacy; and (3) had a lower incidence of adverse events (P = .041). Conclusions: Black Gold DPL Super Photon Skin Rejuvenation offers a significantly higher safety profile and treatment efficacy for pigmented-skin diseases compared to IPL treatment. These promising results suggest potential for its use in clinical practice, but clinical adoption requires future trials.

Neural response properties predict perceived contents and locations elicited by intracranial electrical stimulation of human auditory cortex.

Intracranial electrical stimulation (iES) of auditory cortex can elicit sound experiences with a variety of perceived contents (hallucination or illusion) and locations (contralateral or bilateral side), independent of actual acoustic inputs. However, the neural mechanisms underlying this elicitation heterogeneity remain undiscovered. Here, we collected subjective reports following iES at 3062 intracranial sites in 28 patients (both sexes) and identified 113 auditory cortical sites with iES-elicited sound experiences. We then decomposed the sound-induced intracranial electroencephalogram (iEEG) signals recorded from all 113 sites into time-frequency features. We found that the iES-elicited perceived contents can be predicted by the early high-γ features extracted from sound-induced iEEG. In contrast, the perceived locations elicited by stimulating hallucination sites and illusion sites are determined by the late high-γ and long-lasting α features, respectively. Our study unveils the crucial neural signatures of iES-elicited sound experiences in human and presents a new strategy to hearing restoration for individuals suffering from deafness.

Anti-tumor therapy of glycyrrhetinic acid targeted liposome co-delivery of doxorubicin and berberine for hepatocellular carcinoma.

During the development of hepatocellular carcinoma (HCC), hepatic stellate cells undergo activation and transform into cancer-associated fibroblasts (CAFs) due to the influence of tumor cells. The interaction between CAFs and tumor cells can compromise the effectiveness of chemotherapy drugs and promote tumor proliferation, invasion, and metastasis. This study explores the potential of glycyrrhetinic acid (GA)-modified liposomes (lip-GA) as a strategy for co-delivery of berberine (Ber) and doxorubicin (Dox) to treat HCC. The characterizations of liposomes, including particle size, zeta potential, polydispersity index, stability and in vitro drug release, were investigated. The study evaluated the anti-proliferation and anti-migration effects of Dox&Ber@lip-GA on the Huh-7 + LX-2 cell model were through MTT and wound-healing assays. Additionally, the in vivo drug distribution and anti-tumor efficacy were investigated using the H22 + NIH-3T3-bearing mouse model. The results indicated that Dox&Ber@lip-GA exhibited a nanoscale particle size, accumulated specifically in the tumor region, and was efficiently taken up by tumor cells. Compared to other groups, Dox&Ber@lip-GA demonstrated higher cytotoxicity and lower migration rates. Additionally, it significantly reduced the deposition of extracellular matrix (ECM) and inhibited tumor angiogenesis, thereby suppressing tumor growth. In conclusion, Dox&Ber@lip-GA exhibited superior anti-tumor effects both in vitro and in vivo, highlighting its potential as an effective therapeutic strategy for combating HCC.

Hierarchically decorated magnetic nanoparticles amplify the oxidative stress and promote the chemodynamic/magnetic hyperthermia/immune therapy.

Magnetic nanoparticles (MNPs) are promising in tumor treatments due to their capacity for magnetic hyperthermia therapy (MHT), chemodynamic therapy (CDT), and immuno-related therapies, but still suffer from unsatisfactory tumor inhibition in the clinic. Insufficient hydrogen peroxide supply, glutathione-induced resistance, and high-density extracellular matrix (ECM) are the barriers. Herein, we hierarchically decorated MNPs with disulfide bonds (S-S), dendritic L-arginine (R), and glucose oxidase (GOx) to form a nanosystem (MNPs-SS-R-GOx). Its outer GOx layer not only enhanced the H2O2 supply to produce .OH by Fenton reaction, but also generated stronger oxidants (ONOO-) together with the interfaced R layer. The inner S-S layer consumed glutathione to interdict its reaction with oxidants, thus enhancing CDT effects. Importantly, the generated ONOO- tripled the MMP-9 expression to induce ECM degradation, enabling much deeper penetration of MNPs and benefiting CDT, MHT, and immunotherapy. Finally, the MNPs-SS-R-GOx demonstrated a remarkable 91.7% tumor inhibition in vivo. STATEMENT OF SIGNIFICANCE: Magnetic nanoparticles (MNPs) are a promising tumor therapeutic agent but with limited effectiveness. Our hierarchical MNP design features disulfide bonds (S-S), dendritic L-arginine (R), and glucose oxidase (GOx), which boosts H2O2 supply for ·OH generation in Fenton reactions, produces potent ONOO-, and enhances chemodynamic therapy via glutathione consumption. Moreover, the ONOO- facilitates the upregulation of matrix metalloprotein expression beneficial for extracellular matrix degradation, which in turn enhances the penetration of MNPs and benefits the antitumor CDT/MHT/immuno-related therapy. In vivo experiments have demonstrated an impressive 91.7% inhibition of tumor growth. This hierarchical design offers groundbreaking insights for further advancements in MNP-based tumor therapy. Its implications extend to a broader audience, encompassing those interested in material science, biology, oncology, and beyond.

Sorafenib plus triplet therapy with venetoclax, azacitidine and homoharringtonine for refractory/relapsed acute myeloid leukemia with FLT3-ITD: A multicenter phase 2 study.

BACKGROUND: Patients with relapsed or refractory acute myeloid leukemia (R/R AML) and FLT3-internal tandem duplication (FLT3-ITD) respond infrequently to salvage chemotherapy. OBJECTIVE: To investigate the efficacy of sorafenib plus triplet therapy with venetoclax, azacitidine, and homoharringtonine (VAH) as a salvage therapy in this population. METHODS: This multicenter, single-arm, phase 2 study was conducted at 12 hospitals across China. Eligible patients had R/R AML with FLT3-ITD (aged 18-65 years) who were treated with VAH. The primary endpoint was composite complete remission (CRc) after two cycles. Secondary outcomes included the overall response rate (ORR), safety, and survival. RESULTS: Between July 9, 2020, and March 19, 2022, 58 patients were assessed for eligibility, 51 of whom were enrolled. The median patient age was 47 years (interquartile range [IQR] 31-57). CRc was 76.5% with ORR of 82.4%. At a median follow-up of 17.7 months (IQR, 8.7-24.7), the median duration of CRc was not reached (NR), overall survival was 18.1 months (95% confidence interval [CI], 11.8-NR) and event-free survival was 11.4 months (95% CI, 5.6-NR). Grade 3 or 4 adverse events occurring in ≥10% of patients included neutropenia in 47 (92.2%), thrombocytopenia in 41 (80.4%), anemia in 35 (68.6%), febrile neutropenia in 29 (56.9%), pneumonia in 13 (25.5%), and sepsis in 6 (11.8%) patients. Treatment-related death occurred in two (3.9%) patients. CONCLUSIONS: The sorafenib plus VAH regimen was well tolerated and highly active against R/R AML with FLT3-ITD. This regimen may be a suitable therapeutic option for this population, but larger population trials are needed to be explored. TRIAL REGISTRATION: Clinical Trials Registry: NCT04424147.

Multiomics Analysis Reveals the Chemical and Genetic Bases of Pigmented Potato Tuber.

Anthocyanins and carotenoids determine the diversity of potato tuber flesh pigmentation; here, the underlying chemical and genetic bases were elucidated by multiomics analyses. A total of 31 anthocyanins and 30 carotenoids were quantified in five differently pigmented tubers. Cyanidin and pelargonidin derivatives determined the redness, while malvidin, petunidin, and delphinidin derivatives contributed to purpleness. Violaxanthin derivatives determined the light-yellow color, while zeaxanthin and antheraxanthin derivatives further enhanced the deep-yellow deposition. Integrated transcriptome and proteome analyses identified that F3'5'H highly enhanced anthocyanin biosynthesis in purple flesh and was responsible for metabolic divergence between red and purple samples. BCH2 significantly enhanced carotenoid biosynthesis in yellow samples and along with ZEP, NCED1, and CCD1 genes determined metabolic divergence between light and deep-yellow samples. The weighted correlation network analysis constructed a regulatory network revealing the central role of AN1 in regulating anthocyanin biosynthesis, and 10 new transcription factors related to anthocyanin and carotenoid metabolism regulation were identified. Our findings provide targeted genes controlling tuber pigmentation, which will be meaningful for the genetic manipulation of tuber quality improvement.

Controlled intracellular aggregation of magnetic particles improves permeation and retention for magnetic hyperthermia promotion and immune activation.

Rationale: Magnetic nanoparticles (MNPs) are the most used inorganic nanoparticles in clinics with therapeutic and imaging functions, but the inefficient magneto-thermal conversion efficiency, fast leakage, and uneven distribution impair their imaging sensitivity and therapeutic efficacy in tumors. Methods: Herein, we rationally designed a system containing pH-controllable charge-reversible MNPs (M20@DPA/HA) and negatively charged MMPs with different sizes (M5 and M20), which could induce intracellular aggregation. The dynamic hydrazone bonds with pH controllability were formed by the surface hydrazides on MNPs and aldehydes of hyaluronic acid (HA). Under the acidic pH, intracellular aggregation of the complex composed by M20@DPA/HA and M5 (M5&20), or M20@DPA/HA and M20 (M20&20) were investigated. In addition, the magnetic hyperthermia therapy (MHT) efficiency of tumor cells, tumor-associated macrophages polarization, giant cells formation and immune activation of tumor microenvironment were explored via a series of cell and animal model experiments. Results: Through physical and chemical characterization, the aggregation system (M20&20) exhibited a remarkable 20-fold increase in magnetothermal conversion efficiency compared to individual MNPs, together with enhanced penetration and retention inside the tumor tissues. In addition, it could promote immune activation, including repolarization of tumor-associated macrophages, as well as the formation of giant cells for T cell recruitment. As a result, the M20&20 aggregation system achieved a high degree of inhibition in 4T1 mouse mammary tumor model, with little tumor growth and metastasis after magnetic hyperthermia therapy. Conclusions: A controlled intracellular aggregation system was herein developed, which displayed an aggregation behavior under the acidic tumor microenvironment. The system significantly enhanced MHT effect on tumor cells as well as induced M1 polarization and multinucleated giant cells (MGC) formation of TAM for immune activation. This controlled aggregation system achieved barely tumor growth and metastasis, showing a promising strategy to improve MNPs based MHT on deteriorate cancers.

The effect of electroacupuncture at ST25 on Parkinson's disease constipation through regulation of autophagy in the enteric nervous system.

The effectiveness and safety of electroacupuncture (EA) for constipation have been confirmed by numerous clinical studies and experiments, and there are also studies on the efficacy of EA for Parkinson's disease (PD) motor symptoms. However, there are few researches on EA for PD constipation. Autophagy is thought to be involved in the mechanistic process of EA in the central nervous system (CNS) intervention in Parkinson's pathology. However, whether it has the same effect on the enteric nervous system (ENS) has not been elucidated. Therefore, we investigated whether EA at Tianshu (ST25) acupoint promotes the clearance of α-Syn and damaged mitochondria aggregated in the ENS in a model of rotenone-induced PD constipation. This study evaluated constipation symptoms by stool characteristics, excretion volume, and water content, and the expression levels of colonic ATG5, LC3II, and Parkin were detected by Western Blot (WB) and Real-Time Quantitative PCR (RT-qPCR). The relationship between the location of α-Syn and Parkin in the colonic ENS was observed by immunofluorescence (IF). The results showed that EA intervention significantly relieved the symptoms of rotenone-induced constipation in PD rats, reversed the rotenone-induced down-regulation of colonic ATG5, LC3II, and Parkin expression, and the positional relationship between colonic α-Syn and Parkin proved to be highly correlated. It is suggested that EA might be helpful in treating PD constipation by modulating Parkin-induced mitochondrial autophagy.

Metabolite analysis of soybean oil on promoting astaxanthin production of Phaffia rhodozyma.

BACKGROUND: Astaxanthin is a carotenoid with strong antioxidant property. In addition, it has anti-cancer, anti-tumor, anti-inflammatory and many other functions. The micro-organisms that mainly produce astaxanthin are Haematococcus pluvialis and Phaffia rhodozyma. Compared with H. pluvialis, P. rhodozyma has shorter fermentation cycle and easier to control culture conditions, but the yield of astaxanthin in P. rhodozyma is low. This article studied how to improve the astaxanthin production of P. rhodozyma. RESULTS: The results showed that when 10 mL L-1 soybean oil was added to the culture medium, astaxanthin production increased significantly, reaching 7.35 mg L-1 , which was 1.4 times that of the control group, and lycopene and ß-carotene contents also increased significantly. Through targeted metabolite analysis, the fatty acids in P. rhodozyma significantly increased under the soybean oil stimulation, especially the fatty acids closely related to the formation of astaxanthin esters, included palmitic acid (C16:0), stearic acid (C18:0), oleic acid (C18:1n9), linoleic acid (C18:2n6), α-linolenic acid (C18:3n3) and γ-linolenic acid (C18:3n6), thereby increasing the astaxanthin esters content. CONCLUSION: It showed that the addition of soybean oil can promote the accumulation of astaxanthin by promoting the increase of astaxanthin ester content. © 2022 Society of Chemical Industry.

Two stages of speech envelope tracking in human auditory cortex modulated by speech intelligibility.

The envelope is essential for speech perception. Recent studies have shown that cortical activity can track the acoustic envelope. However, whether the tracking strength reflects the extent of speech intelligibility processing remains controversial. Here, using stereo-electroencephalogram technology, we directly recorded the activity in human auditory cortex while subjects listened to either natural or noise-vocoded speech. These 2 stimuli have approximately identical envelopes, but the noise-vocoded speech does not have speech intelligibility. According to the tracking lags, we revealed 2 stages of envelope tracking: an early high-γ (60-140 Hz) power stage that preferred the noise-vocoded speech and a late θ (4-8 Hz) phase stage that preferred the natural speech. Furthermore, the decoding performance of high-γ power was better in primary auditory cortex than in nonprimary auditory cortex, consistent with its short tracking delay, while θ phase showed better decoding performance in right auditory cortex. In addition, high-γ responses with sustained temporal profiles in nonprimary auditory cortex were dominant in both envelope tracking and decoding. In sum, we suggested a functional dissociation between high-γ power and θ phase: the former reflects fast and automatic processing of brief acoustic features, while the latter correlates to slow build-up processing facilitated by speech intelligibility.

PD-1 engineered cytomembrane cloaked molybdenum nitride for synergistic photothermal and enhanced immunotherapy of breast cancer.

Incomplete tumor ablation and subsequent tumor metastasis usually occur during photothermal anti-tumor processes. The combination of photothermal and immunotherapy has proven to be a promising method to conquer technical challenges. Inhibiting the programmed death ligand-1 (PD-L1)/programmed cell death protein 1 (PD-1) immune pathway represents one of the most successful immunotherapy strategies. Whereas, the PD-L1 expression level significantly differs, leading to a relatively low response rate to the immune checkpoint blockade (ICB) approaches. Therefore, improving the expression level of PD-L1 becomes one potential method to enhance the response rate. Herein, NIH 3T3 cells were educated to steadily express PD-1 protein. Furthermore, the synthesized molybdenum nitride was then coated with PD-1 protein-modified cytomembrane, which endows it with immune checkpoint blocking capability. Moreover, under the irradiation of near-infrared light, the local mild heat released from the molybdenum nitride causes the apoptosis of tumor cells. More importantly, the elevated temperature simultaneously helps elevate the expression level of PD-L1, further enhancing the response rate of ICB. Finally, the PD-1 cytomembrane coatings interact with the upregulated PD-L1, leading to the activation of the immune system. In summary, we confirmed that the PD-1 protein-coated molybdenum nitride could synergistically ablate tumors and avoid metastasis.

Effects of Extraction Technique on the Content and Antioxidant Activity of Flavonoids from Gossypium Hirsutum linn. Flowers.

Cotton is one of the Uyghur medical materials in China and is rich in flavonoids. Flavonoids have important pharmacological effects. The yield of flavonoids in traditional extraction methods is low, which affects the development of flavonoids. Therefore, it is urgent to optimize the extraction techniques. The yield of flavonoids in cotton flowers was effectively improved by response surface methodology, and the highest yield of flavonoids reached 5.66%, and the optimal extraction process conditions were obtained. The DPPH free radical scavenging rate, hydroxyl free radical scavenging rate, superoxide anion free radical scavenging rate, and reducing ability were tested to reflect the antioxidant capacity of flavonoids. The flavonoids had an excellent antioxidant effect. Cell experiments suggested that the flavonoids had the effect of protecting glutamate-induced damage to HT-22 cells. The results of this study provide a theoretical basis for the extraction of cotton flowers flavonoids and the comprehensive evaluation of antioxidant products, as well as the extraction of other plant flavonoids.

Poly-l-lysine derivative-coated black phosphorus as a nanoplatform for photothermal chemotherapy to enhance anti-tumor efficiency.

Severe systemic toxicity and side effects are major obstacles to the success of chemotherapy for tumors. Regardless of the choice of chemotherapy drugs, the safety of drug delivery materials is crucial, and therefore, there have been various efforts to improve the therapeutic effect and the biological safety of drug delivery systems (DDSs). In this study, a dual stimulus-response DDS (PLL-SS@DOX-BP) was constructed based on the biomaterials of black phosphorus (BP) nanosheets and poly-l-lysine (PLL) to enhance the treatment of doxorubicin hydrochloride (DOX) for breast cancer. The PLL derivative was nano-coated on the surface of drug-loaded BP nanosheets, and it prevented premature leakage of the drug and maintained the stability of the DDS. The introduced disulfide bonds and photothermal agent BP enabled the redox and near-infrared responsive drug release of the DDS, and the coated PLL derivative on the nanocarrier decreased premature leakage of the drug before the DDS reached the tumor tissues. The in vitro and in vivo experiments showed that the combination of biomaterial (PLL) and photothermal material (BP nanosheets) exhibited excellent biological safety and remarkable drug delivery capacity. Moreover, the pharmacodynamic studies indicated that PLL-SS@DOX-BP is a powerful vehicle for photothermal therapy in combination with chemotherapy. Compared with chemotherapy alone, the developed DDS displayed enhanced anti-tumor efficiency with decreased systemic toxicity, and thus, it has the potential to be a promising anti-tumor treatment strategy.

Fe(III)-Chelated Polydopamine Nanoparticles for Synergistic Tumor Therapies of Enhanced Photothermal Ablation and Antitumor Immune Activation.

Both the low energy density of near-infrared (NIR) photothermal conversion during treatment and the recurrence and metastasis after local treatment have been the main obstacles and conundrums in polydopamine-mediated tumor photothermal therapy (PTT). Herein, On the basis of the enhancement of NIR absorption by ligand to metal charge transfer (LMCT) in transition-metal complexes and the activation of antitumor immunity by an appropriate concentration of Fe(III) ions, Fe(III)-chelated PDA nanoparticles (Fe-PDA NPs) with high loading and responsive release of iron ions were synthesized through a prechelation-polymerization method. First, Fe(III) chelated with the catechol groups in DA to form a mono-dopa-Fe(III) chelate, and then the polymerization of dopamine was initiated under alkaline conditions. The results revealed that the mono-dopa-Fe(III) chelate was still the main form of the Fe ion existing in Fe-PDA and was able to greatly enhance the light absorption behaviors of PDA in NIR, resulting a superior photothermal conversion ability (η = 55.5%). Moreover, the existence of Fe(III) also gave Fe-PDA a T1-weighted MRI contrast-enhancement performance (r1 = 7.668 mM-1 s-1) and it would enable the accurate ablation of primary tumors in vivo with Fe-PDA under NIR irradiation by means of the guidance of MRI and thermal imaging. Furthermore, Fe-PDA exhibited better H2O2-responsive biodegradability in comparison to PDA and easily released Fe ions in tumors, which could effectively promote the tumor-associated macrophage (TAM) repolarization to the M1 mode. TAM repolarization combined with the immunogenic cell death (ICD) induced by PTT could effectively enhance the efficacy of immunotherapy, preventing tumor recurrence and metastasis. The design of Fe-PDA nanoparticles should provide more inspiration for structural and functional improvements of melanin-based materials in tumor suppression.

A phase 2 study of sorafenib combined with conventional therapies in refractory central nervous system leukemia.

BACKGROUND: Patients with refractory central nervous system leukemia (CNSL) have a dismal prognosis and lack effective therapy. Case reports have shown that sorafenib is effective against brain metastases, including leukemia. METHODS: To explore the efficacy of sorafenib combined with conventional therapies for refractory CNSL, a phase 2 study was conducted. The primary end point was the complete remission rate (CRR) within 8 weeks of treatment. Secondary end points included the overall response rate (ORR), event-free survival (EFS), overall survival (OS), and adverse events (AEs). RESULTS: Twenty-six patients with refractory CNSL were enrolled; they included 17 with isolated CNSL, 7 with hematological relapse, and 2 with another extramedullary relapse. After 8 weeks of treatment, 21 patients achieved complete remission, 2 achieved partial remission, and 3 achieved no remission for a CRR of 80.8% (95% CI, 62.1%-91.5%) and an ORR of 88.5% (95% CI, 71.0%-96.0%). Twenty patients survived, and 6 died. The 2-year EFS and OS rates were 75.0% (95% CI, 54.5%-88.3%) and 76.9% (95% CI, 54.2%-90.4%), respectively. Six patients experienced grade 3 or 4 treatment-related AEs, including moderate chronic graft-vs-host disease (n = 3), grade 3 or 4 acute graft-vs-host disease (n = 2), and grade 3 skin rash (n = 1). No treatment-related deaths occurred during the therapy of refractory CNSL. CONCLUSIONS: Sorafenib combined with conventional therapies is effective and safe for refractory CNSL. LAY SUMMARY: Sorafenib combined with conventional therapies is effective and safe for refractory central nervous system leukemia.

Quality Status Analysis and Intrinsic Connection Research of Growing place, Morphological Characteristics, and Quality of Chinese Medicine: Cyperi Rhizoma (Xiangfu) as a Case Study.

Materials and Methods: The macroscopic characteristics of CR as well as its moisture, ethanol extract, essential oil, total ash, and acid-insoluble ash contents were examined and calculated. In addition, qualitative identification and quantitative determination of α-cyperone, cyperotundone, and nootkatone were simultaneously performed, and a high-performance liquid chromatography (HPLC) fingerprint chromatogram was established. Inductively coupled plasma mass spectrometry and gas chromatography methods recorded in ChP were used to measure the contents of residues of heavy metal and deleterious elements as well as residues of organochlorine pesticide, respectively. Hierarchical cluster analysis and typical canonical correlation analysis were performed using Origin 9.1 and SPSS 23.0 to explore the correlation between CR's growth area, morphological characteristics, and quality. Results: Of the 47 batches of CR analyzed, only 4 collected from the province of Shandong had a flat appearance, which did not accord with the macroscopic characteristics of CR. Overall, only 4 batches met ChP standards for CR. In addition, 30 and 38 batches did not meet the requirements for moisture content and essential oil content, respectively. The similarity values of HPLC fingerprints ranged from 0.568 to 0.986. Results of hierarchical cluster analysis for ethanol extracts, essential oil, α-cyperone, cyperotundone, and nootkatone and the HPLC fingerprints (total peak time and peak area) suggested that the samples could be classified into four clusters, with no significant difference in growth geographic areas among them. Results of canonical correlation analysis indicated that the first canonical pair could represent the correlation between macroscopic characteristics (vector 1) and chemical quality (vector 2), with shorter diameter and length denoting lower ethanol extract content and higher nootkatone content in a single grain of CR. Conclusions: Crude medicinal materials were collected and examined in this study to reflect the overall quality status of CR in China. The methods chosen to detect, calculate, and analyze the quality of CR were suitable to the investigation, and the results are crucial not only for estimating the current quality status of CR, but also for conducting further research into its cultivation, quality assurance, and commodity specification. Besides, this mode of investigation could be used to evaluate other medicines.

Parkinson's disease constipation effect of electroacupuncture at ST25 through colonic motility and enteric neuropathology.

Background: The enteric nervous system (ENS) plays a central role in developing Parkinson's disease (PD) constipation, and the regulation of the ENS may be a key component in treating PD constipation. Electroacupuncture (EA) can effectively treat constipation symptoms in PD, but research on its specific mechanisms, especially in terms of ENS, is relatively lacking. Therefore, we investigated whether EA at ST25 promotes the restoration of ENS structure and colonic motor function in the rotenone-induced PD constipation rat model. Methods: In this study, we evaluated constipation symptoms by stool characteristics, excretion and water volume, and whole gut transit time and observed colonic motility regulation through colonic motion detection and pathological changes in the colonic myenteric nervous plexus by transmission electron microscopy and immunofluorescence staining. Results: EA significantly improved the constipation symptoms and positively adjusted the colonic motility in rotenone-induced PD constipation rats. At the same time, EA reversed the rotenone-induced colonic myenteric nervous plexus injury and regulated the ratio of inhibitory and excitatory neurotransmitters. Conclusion: Our results indicate that EA treatment of PD constipation may be mediated through the adjustment of ENS.