Electroacupuncture facilitates vascular normalization by inhibiting Glyoxalase1 in endothelial cells to attenuate glycolysis and angiogenesis in triple-negative breast cancer.

Recent therapeutic strategies for the treatment of triple-negative breast cancer (TNBC) have shifted the focus from vascular growth factors to endothelial cell metabolism. This study highlights the underexplored therapeutic potential of peri-tumoral electroacupuncture, a globally accepted non-pharmacological intervention for TNBC, and molecular mechanisms. Our study showed that peri-tumoral electroacupuncture effectively reduced the density of microvasculature and enhanced vascular functionality in 4T1 breast cancer xenografts, with optimal effects on day 3 post-acupuncture. The timely integration of peri-tumoral electroacupuncture amplified the anti-tumor efficacy of paclitaxel. Multi-omics analysis revealed Glyoxalase 1 (Glo1) and the associated methylglyoxal-glycolytic pathway as key mediators of electroacupuncture-induced vascular normalization. Peri-tumoral electroacupuncture notably reduced Glo1 expression in the endothelial cells of 4T1 xenografts. Using an in vivo matrigel plug angiogenesis assay, we demonstrated that either Glo1 knockdown or electroacupuncture inhibited angiogenesis. In contrast, Glo1 overexpression increased blood vessel formation. In vitro pharmacological inhibition and genetic knockdown of Glo1 in human umbilical vein endothelial cells inhibited proliferation and promoted apoptosis via downregulating the methylglyoxal-glycolytic pathway. The study using the Glo1-silenced zebrafish model further supported the role of Glo1 in vascular development. This study underscores the pivotal role of Glo1 in peri-tumoral electroacupuncture, spotlighting a promising avenue for enhancing vascular normalization and improving TNBC treatment outcomes.

Treatment of severe rash caused by crizotinib with both traditional Chinese medicine and Western medicine: Two case reports and literature review.

RATIONALE: Lung adenocarcinoma is the most common pathologic pattern of lung cancer. During the past decades, a number of targeted agents have been explored to treat advanced lung adenocarcinoma. Recently, Crizotinib, the antagonist of anaplastic lymphoma kinase (ALK), has been widely used in ALK-rearranged lung cancer treatment. Crizotinib is generally well tolerated while its most frequent adverse events include visual disorders, gastrointestinal disturbances, cardiac and endocrine abnormalities. Rash caused by crizotinib is rarely seen, and there are few case reports of severe rash caused by crizotinib. PATIENT CONCERNS AND DIAGNOSES: Here we report cases of an 81-year-old man and a 66-year-old woman with ALK-rearranged advanced lung adenocarcinoma. When patients came to our department, they both had crizotinib-induced severe rash. INTERVENTIONS: Crizotinib was initiated as the 1st-line treatment without other therapies. We treated severe rash with traditional Chinese medicine (TCM) therapy called Zhiyang Pingfu liquid along with Western medicine. Zhiyang Pingfu liquid consists of Scutellaria baicalensis 20 g, Portulaca oleracea 30 g, Cortex Dictamni 30 g, Sophora flavescens 30 g, and other substances. Western medicine includes Minocycline hydrochloride tablets and Aprepitant capsules. OUTCOMES: Both patients achieved a partial response when treated with crizotinib, and suffered from severe rash. With Zhiyang Pingfu liquid and Western medicine, their rash gradually disappeared with no sign of cancer progression. Also the male patient did not relieve after taking only antibiotics (standard therapy) and anti-allergic medicine. LESSONS: Despite the dramatic benefit of crizotinib for patients with ALK rearrangement, crizotinib-induced severe rash needs to be dealt with caution. This is the 1st case in which TCM and Western medicine are used to successfully treat crizotinib-induced severe rash. The mechanism of crizotinib-induced rash deserves further attention in future research.

Ru(bpy)32+-Silica@Poly-L-lysine-Au as labels for electrochemiluminescence lysozyme aptasensor based on 3D graphene.

In this work, the feasibility of a novel sensitive electrochemiluminescence aptasensor for the detection of lysozyme using Ru(bpy)32+-Silica@Poly-L-lysine-Au (RuSiNPs@PLL-Au) nanocomposites labeling as an indicator was demonstrated. The substrate electrode of the aptasensor was prepared by depositing gold nanoparticles (AuNPs) on 3D graphene-modified electrode. The lysozyme binding aptamer (LBA) was attached to the 3D graphene/AuNPs electrode through gold-thiol affinity, hybridized with a complementary single-strand DNA (CDNA) of the lysozyme aptamer labeled by RuSiNPs@PLL-Au as an electrochemiluminescence intensity amplifier. Thanks to the synergistic amplification of the 3D graphene, the AuNPs and RuSiNPs@PLL-Au NPs linked to Ru(bpy)32+-ECL further enhanced the ECL intensity of the aptasensor. In presence of lysozyme, the CDNA segment of the self-assembled duplex was displaced by the lysozyme, resulting in decreased electrochemiluminescence signal. Under the optimized conditions, the decrease in electrochemiluminescence intensity varied proportionally with the logarithmic concentration of the lysozyme from 2.25 × 10-12 to 5.0 × 10-8 mol L-1, and the detection limit was estimated to 7.5 × 10-13 mol L-1. The aptasensor was further tested in real samples and found reliable for the detection of lysozyme, thus holding great potential application in food safety researches and bioassay analysis.

[Treatment of EGFRIs-related Skin Adverse Reactions by Zhiyang Pingfu Lotion].

Objective To observe the curative effect of Zhiyang Pingfu Lotion (ZPL) for its ex- ternal application in treatment of epidermal growth factor receptor inhibitors (EGFRIs)-related acneiform rash, cutaneous pruritus , xerosis cutis , and nail changes , as well as to evaluate its safety and patients' satisfaction. Methods Recruited were 201 patients with confirmed pathological diagnosis, who had acne- iform rash after using EGFRIs. They were assigned to the treatment group (131 cases) and the control group (70 cases) by random digit table. Patients in the treatment group were externally applied with self- formulated ZPL based on principles of Western medical standards, while those in the control group were externally applied with blank drugs plus conventional Western medicine standard. The therapeutic course for all was 14 days. Changes in rash degree, cutaneous pruritus, xerosis cutis, and nails were observed in both groups before and after treatment. Blood routines as well as liver and kidney function tests were performed in both groups before and after treatment. Follow-up visit was also conducted during progression-free survival (PFS). Results A total of 185 patients finished this clinical trial. Ten dropped out in the treatment group and 6 in the control group. The effective rates of rash degree, cutaneous pruritus, xerosis cutis, and nail changes were 90.1 % (109/121 ), 57.9% (70/121 ), 57. 9% (70/121 ), and 16. 5% (20/121) in the treatment group, respectively. They were 14. 1% (9/64), 6. 3% (4/64), 1. 6% (1164), and 0 (0/64) in the control group, respectively. Significant difference existed in all these indices between the two groups (X² = 105. 1022, 51. 3312, 59. 1777; P <0. 05). No serious drug-related adverse events occurred during clinical observation, with relatively better safety. The satisfaction was 95. 40% (125/131) in the treatment group and 57. 1 % (40/70) in the control group. No statistical difference in PFS was observed between the two groups (X² = 2. 006, P > 0. 05). Conclusions ZPL had significantly curative effect in treatment of EGFRIs-related skin adverse reactions, with no obvious adverse reactions. Howev- er, more randomized control trials are needed to verify these findings.

Chiral separation and absolute configurations of two pairs of racemic polyprenylated benzophenones from Hypericum sampsonii.

(±) Sampsonins A-B (1-2), two pairs of racemic polyprenylated benzophenones, were isolated from the aerial parts of Hypericum sampsonii and successfully separated by chiral HPLC column. Their structures were elucidated by spectroscopic analyses, X-ray diffraction analysis, and quantum chemical calculation of ECD method. Besides, the plausible biogenetic pathways of 1-2 were proposed, and all of them were evaluated for RXRα transcriptional-inhibitory activities and cytotoxicity against HeLa cells.

Dioxasampsones A and B, two polycyclic polyprenylated acylphloroglucinols with unusual epoxy-ring-fused skeleton from Hypericum sampsonii.

Dioxasampsones A and B (1 and 2), two new polycyclic polyprenylated acylphloroglucinols with an unusual epoxy-ring-fused skeleton by new ways of cyclization, along with a new nor-PPAPs hypersampson R (3) with the loss of C-31-33 in isopentenyl, were isolated from the aerial parts of Hypericum sampsonii. 1 possessed an unexpected hexacyclic skeleton with a rare 2,7-dioxabicyclo[2.2.1]heptane moiety, and 2 featured a unique tetrahydrofuro[3,4-b]furan-fused tricycle[4.3.1.1(5,7)]undecane skeleton. The gross structures of the new compounds were determined by extensive NMR spectroscopic methods. Their absolute configurations were deduced by single-crystal X-ray diffraction and ECD calculations.

The usefulness of xuefu zhuyu tang for patients with angina pectoris: a meta-analysis and systematic review.

Objective. To evaluate the efficacy of Xuefu Zhuyu Tang (XFZYT) for treating angina pectoris (AP). Methods. Six databases were searched (up to December, 2013). Eligible randomized controlled trials (RCTs) evaluating the efficiency of XFZYT plus traditional antianginal medications (TAMs) compared with TAMs alone in patients with AP were included. The outcomes were relief of anginal symptoms (RAS) and improvement of electrocardiogram (ECG) and blood high-density lipoprotein cholesterol (HDL-C) level. Result. Finally 14 RCTs were included. There were evidences that XFZYT combined with TAMs was more effective in improving RAS (RR = 1.29; 95% CI = [1.20, 1.38]), ECG (RR = 1.37; 95% CI = [1.22, 1.54]), and blood HDL-C level (MD = 0.29 mmol/L; 95% CI = [0.23, 0.35]) compared with TAMs alone. Our meta-analysis also showed the pooled number needed to treat (NNT) of the group with stable angina pectoris (SAP) was smaller in improving RAS (4.2 versus 5.7) and ECG (3.1 versus 5.5) compared with the group with both SAP and unstable angina pectoris (UAP). Conclusion. Combination therapy with XFZYT and TAMs is more effective in treating AP compared with TAMs alone. And XFZYT may be a more suitable choice for the treatment of SAP. However, the findings should be interpreted with caution due to the mediocre methodological quality of the included RCTs.

A new approach to quantify spatial distribution of biofilm kinetic parameters by in situ determination of oxygen uptake rate (OUR).

In order to guide the rational optimization of biofilm reactor design and operation in wastewater treatment, it is essential to comprehend the biokinetic behavior of microorganisms, especially with its depth variation, in biofilms. However, no fast and accurate methods have been established for measuring the stratification of biokinetic parameters in biofilm systems up to now. In this paper, a new approach was presented to quantify the spatial distribution of biokinetic parameters in biofilms with a result demonstration. A multispecies biofilm at endogenous respiration was subjected to a pulse of substrates at various locations. An oxygen microelectrode structurally combined with an additional micropipette for substrate injection was constructed to monitor the in situ OUR (oxygen uptake rate) by measuring the dissolved oxygen concentration with time. Based on the oxygen concentration profiles versus times at a series of substrate concentrations, the spatial distribution of biokinetic parameters, biomassyield coefficient (YH), Monod half-saturation coefficient for substrate (KH,S), and maximum specific growth rate (muH,max) were quantified. The demonstration of its utility showed that YH was within the 0.437-0.449 g (COD in cell)/g COD range, with only a slight difference and no regular change in the spatial distribution. Meanwhile, the results showed that the distribution of muH,max varied from 9.18 day(-1) at the surface layer of the biofilm to 1.69 day(-1) at the substratum layer of the biofilm with a decrease of 80% due to the reduction of biomass activity orthe diverse distribution of microbial species. Additionally, an opposite change tendency of KH,S was found, which increased from 37 mg COD/L at the surface layer of the biofilm to 45 mg COD/L at the substratum layer of the biofilm, indicating larger mass transport limitations with penetration into the biofilm. Compared with high heterogeneity in the biofilm depth, the distribution of biokinetic parameters was less heterogeneous in the horizontal direction at the same depth. In summary,the results provide experimental evidence necessary for biofilm modeling, which could not be accomplished in the past, and enable us to obtain a clearer biokinetic description of the biofilm.

[In-situ determination of endogenous decay rate of heterotrophic biofilm by microelectrodes].

A separated oxygen microelectrode was constructed, based on the improved structure, to determine the oxygen distribution in biofilm at an endogenous state. Based on the diffusion-reaction model, the endogenous decay rate was evaluated by curve-fitting with the measured oxygen profiles. The results showed that the fluctuation range of output signal of oxygen microelectrode was reduced from (1.64 +/- 0.25) nA to (1.53 +/- 0.06) nA, the signal became stable with the fluctuation rejection ratio of 19.41 dB after the structural optimization. The endogenous respiration rate and the endogenous decay rate of heterotrophic biofilm were evaluated to be 2.979 mg x h(-1) and 0.0059 h(-1).