Recent progress for chiral stationary phases based on chiral porous materials in high-performance liquid chromatography and gas chromatography separation.

Chirality is a fundamental property of nature. Separation and analysis of racemates are of great importance in the fields of medicine and the production of chiral biopharmaceutical intermediates. Chiral chromatography has the characteristics of a wide separation range, fast separation speed, and high efficiency. The development and preparation of novel chiral stationary phases with good chiral recognition and separation capacity is the core and key of chiral chromatographic separation and analysis. In this work, the representative research progress of novel chiral porous crystal materials including chiral covalent organic frameworks, chiral porous organic cages, chiral metal-organic frameworks, and chiral metal-organic cages used as chiral stationary phases of capillary gas chromatography and high-performance liquid chromatography over the last 4 years is reviewed in detail. The chiral recognition and separation properties of the representative studies in this review are also introduced and discussed.

Distinct characteristics of the gut virome in patients with osteoarthritis and gouty arthritis.

BACKGROUND/PURPOSE(S): The gut microbiota and its metabolites play crucial roles in pathogenesis of arthritis, highlighting gut microbiota as a promising avenue for modulating autoimmunity. However, the characterization of the gut virome in arthritis patients, including osteoarthritis (OA) and gouty arthritis (GA), requires further investigation. METHODS: We employed virus-like particle (VLP)-based metagenomic sequencing to analyze gut viral community in 20 OA patients, 26 GA patients, and 31 healthy controls, encompassing a total of 77 fecal samples. RESULTS: Our analysis generated 6819 vOTUs, with a considerable proportion of viral genomes differing from existing catalogs. The gut virome in OA and GA patients differed significantly from healthy controls, showing variations in diversity and viral family abundances. We identified 157 OA-associated and 94 GA-associated vOTUs, achieving high accuracy in patient-control discrimination with random forest models. OA-associated viruses were predicted to infect pro-inflammatory bacteria or bacteria associated with immunoglobulin A production, while GA-associated viruses were linked to Bacteroidaceae or Lachnospiraceae phages. Furthermore, several viral functional orthologs displayed significant differences in frequency between OA-enriched and GA-enriched vOTUs, suggesting potential functional roles of these viruses. Additionally, we trained classification models based on gut viral signatures to effectively discriminate OA or GA patients from healthy controls, yielding AUC values up to 0.97, indicating the clinical utility of the gut virome in diagnosing OA or GA. CONCLUSION: Our study highlights distinctive alterations in viral diversity and taxonomy within gut virome of OA and GA patients, offering insights into arthritis etiology and potential treatment and prevention strategies.

Qingfei mixture mitigates immunosuppression of tumor microenvironment in non-small cell lung cancer by blocking stat1/Ido1-mediated tryptophan-kynurenine pathway.

Programmed death-1 (PD-1) acts as a T cell checkpoint and is important in controlling T cell exhaustion. Blocking the intercommunication across PD-1 and PD-L1 is promising for advanced lung cancer treatment. However, the response rate requires being strengthened. This study aimed to determine whether the combination treatment of Qingfei mixture (QFM) and PD-1 inhibitor could improve the sensitivity of monoclonal antibody by regulating STAT1/IDO1-mediated tryptophan (Trp)-kynurenine (Kyn) pathway. The in vivo imaging system, immunofluorescence, hematoxylin-eosin staining, TUNEL, flow cytometry, HPLC, and ELISA were used to estimate the anti-tumor effects in LLC-luc tumor-bearing C57BL/6 mice treated with QFM, PD-1 inhibitor, 2-NP (enhancer of STAT1 transcription), and FICZ (AhR agonist) alone or in combination. IFN-γ-mediated A549 and LLC cells were treated with QFM-containing serum and fludarabine (FLU, STAT1 inhibitor), and cell viability, apoptosis, and Kyn content were then evaluated using CCK-8 assays, flow cytometry, and HPLC assays, respectively. Additionally, the expressions of STAT1, IDO1, AhR, NFATc1, TRIP12, PD-1, and PD-L1 were measured in vivo and in vitro. We found QFM increased the anti-cancer actions of PD-1 inhibitors by increasing the CD8+IFNγ+ T cells infiltration and decreasing the ratio of Kyn/Trp. Besides, QFM-containing serum suppressed the proliferation and promoted apoptosis in A549 and LLC cells, meanwhile, FLU boosted the effects of QFM-containing serum. Moreover, the suppression of tumor growth in the combination therapy was attenuated in the mice receiving 2-NP or FICZ. The occurrence of the above results was accompanied by a decrease in STAT1, IDO1, AhR, PD-1, and PD-L1 expressions. Collectively, the findings suggested that QFM may increase the influences of PD-1 inhibitors at least partially by blocking the STAT1/IDO1-mediated tryptophan-kynurenine pathway in lung cancer.

Qingfei mixture modulates the immune responses in lung cancer through modulating mTOR signaling and gut microbiota-derived short-chain fatty acids.

Lung cancer ranks among the primary contributors to cancer-related fatalities on a global scale. Multiple research investigations have demonstrated that there exists a dysbiosis within the intestinal bacteria and short-chain fatty acids (SCFAs) is linked with immune responses in lung cancer. Qingfei mixture (QFM) has been widely used in treating lung cancer, yet the active ingredients and roles of the QFM on immune responses by targeting gut microbiota remain to be elucidated. The chemical constituents of QFM were qualitatively examined by UPLC/Q-TOF-MS. Additionally, we evaluated the therapeutic impact of the organic substance QFM on lung cancer, aiming to elucidate its mechanisms for improving the tumor-immune microenvironment. Herein, we constructed a Lewis lung carcinoma (LLC)-bearing mice model with QFM treatment to observe tumor growth and immune cell changes. Then, the feces were collected and a combinatory study using metagenomes, non-targeted metabonomics, and targeted metabonomics of SCFAs was performed. In vitro experiments have been conducted to estimate the roles of acetate and sodium propionate in CD8+ T cells. Furthermore, we treated tumor-bearing mice with QFM, QFM + MHY1485 (an mTOR activator), and QFM + an antibiotic mixture (ABX) to explore the potential therapeutic benefit of regulation of the tumor microenvironment. A total of 96 compounds were obtained from QFM by UPLC/Q-TOF-MS. Besides, the findings demonstrated that QFM exhibited significant efficacy against lung cancer, manifesting in reduced tumor growth and improved immune responses. In investigating its mechanisms, we integrated gut microbiota sequencing and fecal metabolomics, revealing that QFM effectively restored disruptions in gut microbiota and SCFAs in mice with lung cancer. QFM, acetate, or sodium propionate contributed to the up-regulation of IFN-γ, Gzms-B, perforin, IL-17, IL-6, IL-12, TNF-α expressions and decreased HDAC and IL-10 levels in vitro and in vivo. Moreover, MHY1485 and ABX weakened the effects of QFM on immunomodulation. Collectively, these results suggest that QFM may facilitate immune responses in the LLC-bearing mice via regulating the gut microbiota-derived SCFAs at least partially through targeting the mTOR signaling pathway.

Dietary fiber intake and its association with diabetic kidney disease in American adults with diabetes: A cross-sectional study.

BACKGROUND: Dietary fiber (DF) intake may have a protective effect against type 2 diabetes (T2D); however, its relationship with diabetic kidney disease (DKD) remains unclear. AIM: To investigate the potential association between DF intake and the prevalence of DKD in individuals diagnosed with T2D. METHODS: This cross-sectional study used data from the National Health and Nutrition Examination Survey collected between 2005 and 2018. DF intake was assessed through 24-h dietary recall interviews, and DKD diagnosis in individuals with T2D was based on predefined criteria, including albuminuria, impaired glomerular filtration rate, or a combination of both. Logistic regression analysis was used to assess the association between DF intake and DKD, and comprehensive subgroup and sensitivity analyses were performed. RESULTS: Among the 6032 participants, 38.4% had DKD. With lower DF intake-T1 (≤ 6.4 g/1000 kcal/day)-as a reference, the adjusted odds ratio for DF and DKD for levels T2 (6.5-10.0 g/1000 kcal/day) and T3 (≥ 10.1 g/1000 kcal/day) were 0.97 (95%CI: 0.84-1.12, P = 0.674) and 0.79 (95%CI: 0.68-0.92, P = 0.002), respectively. The subgroup analysis yielded consistent results across various demographic and health-related subgroups, with no statistically significant interactions (all P > 0.05). CONCLUSION: In United States adults with T2D, increased DF intake may be related to reduced DKD incidence. Further research is required to confirm these findings.

Potential for the development of Taraxacum mongolicum aqueous extract as a phytogenic feed additive for poultry.

Introduction: Taraxacum mongolicum (TM) is a kind of medicinal and edible homologous plant which is included in the catalogue of feed raw materials in China. It is rich in polyphenols, flavonoids, polysaccharides and other active substances, and shows many benefits to livestock, poultry and aquatic products. The study aimed to assess the potential of TM aqueous extract (TMAE) as a substitute for poultry AGPs. Methods: A total of 240 one-day-old Arbor Acker broilers were randomly assigned to four groups and fed a basal diet (Con) supplemented with 500, 1000, and 2000 mg/kg TMAE (Low, Medium, and High groups). The growth performance of the broilers was measured on day 21 and day 42. At the end of the trial, the researchers measured slaughter performance and collected serum, liver, spleen, ileum, and intestinal contents to investigate the effects of TMAE on serum biochemistry, antioxidant capacity, immune function, organ coefficient, intestinal morphology, flora composition, and short-chain fatty acids (SCFAs). Results: The results showed that broilers treated with TMAE had a significantly higher average daily gain from 22 to 42 days old compared to the Con group. Various doses of TMAE resulted in different levels of improvement in serum chemistry. High doses increased serum alkaline phosphatase and decreased creatinine. TMAE also increased the antioxidant capacity of serum, liver, and ileum in broilers. Additionally, middle and high doses of TMAE enhanced the innate immune function of the liver (IL-10) and ileum (Occludin) in broilers. Compared to the control group, the TMAE treatment group exhibited an increase in the ratio of villi length to villi crypt in the duodenum. TMAE increased the abundance of beneficial bacteria, such as Alistipes and Lactobacillus, while reducing the accumulation of harmful bacteria, such as Colidextracter and Sellimonas. The cecum's SCFAs content increased with a medium dose of TMAE. Supplementing broiler diets with TMAE at varying doses enhanced growth performance and overall health. The most significant benefits were observed at a dose of 1000 mg/kg, including improved serum biochemical parameters, intestinal morphology, antioxidant capacity of the liver and ileum, immune function of the liver and ileum, and increased SCFAs content. Lactobacillus aviarius, norank_f_norank_o__Clostridia_UCG-014, and Flavonifractor are potentially dominant members of the intestinal microflora. Conclusion: In conclusion, TMAE is a promising poultry feed additive and 1000 mg/kg is an effective reference dose.

Itemized determination of As, Sb, Bi, Se, and Ge in graphite sample by HG-AFS with high-temperature microwave digestion.

In this paper, we optimized a method for fast and accurate determination of five impurity elements (As, Sb, Bi, Se, and Ge) in graphite samples to overcome the shortcomings of existing methods, such as complicated equipment, cumbersome process, multiple-time preparation, separate determination, and large error in results. Graphite samples were digested with HNO3-H2SO4-HClO4-HF in a high-temperature and high-pressure microwave digestion apparatus, and the elements were extracted and determined separately by AFS (atomic fluorescence spectrometry). There is no element loss during the processing and analysis of this method. The spike recoveries (As: 90.30%-102.3%, Sb: 90.73%-110.0%, Bi: 90.00%-99.67%, Se: 93.33%-110.0%, Ge: 92.26%-104.2%) and precision (RSD%; As: 1.34%-8.96%, Sb: 2.67%-7.10%, Bi: 1.83%-4.58%, Se: 0.36%-3.25%, Ge: 4.41%-8.65%) meet the requirements of the corresponding quality specifications. The method has some advantages (such as no elemental loss, fast testing, strong element targeting, and accurate results), and thus can achieve batch determination of graphite samples. The optimized method for graphite sample and final solution preparations can be used for diverse spectrometric technologies, and that for spectrometer conditions have reference value for HG-AFS instruments.

Significance of phosphate adsorbed on the cellular surface as a storage pool and its regulation in marine microalgae.

The increasing prevalence of phosphorus limitation in coastal waters has drawn attention to the bioavailability of cellular surface-adsorbed phosphorus (SP) as a reservoir of phosphorus in phytoplankton. This study examined the storage, utilization, and regulation of SP in the coastal waters of the East China Sea, as well as three cultivated algal bloom species (Skeletonema marinoi, Prorocentrum shikokuense, and Karenia mikimotoi) prevalent in the area. SP accounted for 14.3%-45.5% of particulate phosphorus in the field and laboratory species. After the depletion of external phosphate, the studied species can rapidly transport SP within 3-24 h. The storage of SP is regulated by both external phosphate conditions and the internal growth stage of cells, but it is not influenced by the various cellular surface structures of the studied species. This study highlights the significance of SP as a crucial phosphorus reservoir and the potential use of the SP level as an indicator of phosphorus deficiency in phytoplankton.

Ablation of Shank1 Protects against 6-OHDA-induced Cytotoxicity via PRDX3-mediated Inhibition of ER Stress in SN4741 Cells.

BACKGROUND: Postsynaptic density (PSD) is an electron-dense structure that contains various scaffolding and signaling proteins. Shank1 is a master regulator of the synaptic scaffold located at glutamatergic synapses, and has been proposed to be involved in multiple neurological disorders. METHODS: In this study, we investigated the role of shank1 in an in vitro Parkinson's disease (PD) model mimicked by 6-OHDA treatment in neuronal SN4741 cells. The expression of related molecules was detected by western blot and immunostaining. RESULTS: We found that 6-OHDA significantly increased the mRNA and protein levels of shank1 in SN4741 cells, but the subcellular distribution was not altered. Knockdown of shank1 via small interfering RNA (siRNA) protected against 6-OHDA treatment, as evidenced by reduced lactate dehydrogenase (LDH) release and decreased apoptosis. The results of RT-PCR and western blot showed that knockdown of shank1 markedly inhibited the activation of endoplasmic reticulum (ER) stress associated factors after 6-OHDA exposure. In addition, the downregulation of shank1 obviously increased the expression of PRDX3, which was accompanied by the preservation of mitochondrial function. Mechanically, downregulation of PRDX3 via siRNA partially prevented the shank1 knockdowninduced protection against 6-OHDA in SN4741 cells. CONCLUSION: In summary, the present study has provided the first evidence that the knockdown of shank1 protects against 6-OHDA-induced ER stress and mitochondrial dysfunction through activating the PRDX3 pathway.

Functionalizing Separator by Coating a Lithiophilic Metal for Dendrite-Free Anode-free Lithium Metal Batteries.

A stable anode-free lithium metal battery (AFLMB) is accomplished by the adoption of a facile fabricated amorphous antimony (Sb)-coated separator (SbSC). The large specific surface area of the separator elevates lithium (Li)-Sb alloy kinetic, improving Li wetting ability on pristine copper current collector (Cu). When tested with LiNi0.8 Mn0.1 Co0.1 O2 (NMC811) as cathode, the full cell with SbSC demonstrates low nucleation overpotential with compact, dendrite-free and homogeneous Li plating, and exhibits a notable lithium inventory retention rate (LIRR) of 99.8 % with capacity retention of 93.6 % after 60 cycles at 0.5 C-rate. Conversely, full cells containing pristine separator/Cu (i. e., SC) and pristine separator/Sb-coated current collector (i. e., SSbC) display poor cycling performances with low LIRRs. Density functional theory corroborates the nucleation behaviours observed during in-situ half-cell Li deposition. Functionalizing polymeric separator by metallic coating in AFLMB is a novel approach in improving the cycle life of an AFLMB by promoting homogeneous Li plating behavior. This innovative approach exemplifies a promising applicability for uniform Li-plating behavior to achieve a longer cycle life in AFLMB.

The effect of soil environmental factors on the yield and quality of Pueraria lobata.

Pueraria lobata is a typical medicinal and edible plant with great market value and demand, thus exploring the relationship between soil environmental factors and the yield and quality of Pueraria lobata is of great significance for its high-value cultivation. In this study, using the Guige 1 variety (Pueraria montana var. Thomsonii) selected by our research group as the material to compare the effects of five soil types, endophytes in three parts of Pueraria lobata and two fertilizers on its yield and quality. The results showed that the comprehensive evaluation effect of five soil types on the yield and quality of Guige 1 was as follow: red-yellow mixed soil (RYMS) > black loam soil (BLS) > sandy loam soil (SLS) > sandy loam soil waterlogging (SLSW) > yellow soil compaction soil (YSCS); the descending order of endophyte types and quantities is in BLS > RYMS > SLS > YSC > SLSW; applying General Compound Fertilizers (GCF) in RYMS is more suitable for the rapid expansion of Guige 1 than Organic-Slow-Release-Fertilizers (OSRF). The high potassium content in RYMS and high effective phosphorus content in BLS are positively correlated with the content of starch and isoflavone in Pueraria lobata. The conclusion is that the high potassium and available phosphorus content in RYMS and BLS, as well as the rich types and quantities of endophytic bacteria, are positively correlated with the yield and quality of Pueraria lobata. The research results have important guiding significance for the high-value cultivation of Pueraria lobata.

Green Vertical-Cavity Surface-Emitting Lasers Based on InGaN Quantum Dots and Short Cavity.

Room temperature low threshold lasing of green GaN-based vertical cavity surface emitting laser (VCSEL) was demonstrated under continuous wave (CW) operation. By using self-formed InGaN quantum dots (QDs) as the active region, the VCSEL emitting at 524.0 nm has a threshold current density of 51.97 A cm-2, the lowest ever reported. The QD epitaxial wafer featured with a high IQE of 69.94% and the δ-function-like density of states plays an important role in achieving low threshold current. Besides, a short cavity of the device (~ 4.0 λ) is vital to enhance the spontaneous emission coupling factor to 0.094, increase the gain coefficient factor, and decrease the optical loss. To improve heat dissipation, AlN layer was used as the current confinement layer and electroplated copper plate was used to replace metal bonding. The results provide important guidance to achieving high performance GaN-based VCSELs.

Partially Neutralized Polyacrylic Acid as an Efficient Binder for Aqueous Ceramic-Coated Separators for Lithium-Ion Batteries.

A partially neutralized polyacrylic acid (Pn-PAA) is used for coating sub-micron-sized α-alumina on a conventional microporous polyolefin separator, fabricating a ceramic-coated separator (CCS). Pn-PAA acts as a dispersant and binder by adsorbing itself on alpha(α)-alumina surfaces under acidic condition through the columbic interaction, providing a repulsive force to disperse fine alumina in aqueous suspension, and binds alumina strongly on plasma-treated separator through hydrogen bonding. This CCS shows favorable wettability in carbonate-based liquid electrolyte and ionic conduction due to the high hydrophilicity of Pn-PAA and alumina. With that, this study found that Pn-PAA-made-CCS yields a substantial adhesion strength of ~106 N/m with enhanced cycle stability, a specific capacity of 145.0 mAh/g after 200 cycles at 1 C at room temperature in half cells (LFP/Li metal).

Spatial timing of circulating seasonal influenza A and B viruses in China from 2014 to 2018.

Major outbreaks of influenza virus occurred in China in 2017-2018. To describe the pattern of influenza circulation and timing of seasonal epidemics, we analyzed data from influenza-like illness (ILI) specimens on surveillance wards of sentinel hospitals during 2014-2018. Among 1,890,084 ILI cases, 324,211 (17.2%) tested positive for influenza. Influenza A virus (particularly A/H3N2), which circulates annually, was detected in 62% of cases, compared with influenza B virus in 38% of cases. The detection rate of A/H1N1, A/H3N2, B/Victoria, and B/Yamagata viruses were 3.56%, 7.07%, 2.08%, and 3.45%, respectively. Influenza prevalence was generally stable over the four years analyzed, but obvious outbreaks occurred in 2015-2016 (17.28%) and 2017-2018 (22.67%), with B/Victoria and B/Yamagata contributing to these outbreaks, respectively. In the south, a characteristic peak in infections was detected in the summer (week 23-38), which was not detected in the north. Influenza B was found high frequency in school-age children (5-14 years) with 4.78% of B/Victoria and 6.76% of B/Yamagata. Therefore, the epidemiological characteristics of seasonal influenza were complex in China during 2014-2018, presenting distinctions in region, season, and susceptible population. These findings underline the importance of enhancing year-round influenza surveillance and provide a reference for the timing and variety of influenza vaccination.

Intra-Specific Variation in Desiccation Tolerance of Citrus sinensis 'bingtangcheng' (L.) Seeds under Different Environmental Conditions in China.

Intra-specific variation in seed storage behaviour observed in several species has been related to different maternal environments. However, the particular environmental conditions and molecular processes involved in intra-specific variation of desiccation tolerance remain unclear. We chose Citrus sinensis 'bingtangcheng' for the present study due to its known variability in desiccation tolerance amongst seed lots. Six seed lots of mature fruits were harvested across China and systematically compared for drying sensitivity. Annual sunshine hours and average temperature from December to May showed positive correlations with the level of seed survival of dehydration. Transcriptional analysis indicated significant variation in gene expression between relatively desiccation-tolerant (DT) and -sensitive (DS) seed lots after harvest. The major genes involved in late seed maturation, such as heat shock proteins, showed higher expression in the DT seed lot. Following the imposition of drying, 80% of stress-responsive genes in the DS seed lot changed to the stable levels seen in the DT seed lot prior to and post-desiccation. However, the changes in expression of stress-responsive genes in DS seeds did not improve their tolerance to desiccation. Thus, higher desiccation tolerance of Citrus sinensis 'bingtangcheng' seeds is modulated by the maternal environment (e.g., higher annual sunshine hours and seasonal temperature) during seed development and involves stable expression levels of stress-responsive genes.

Percutaneous Full Endoscopic Management of Spinal Foraminal Schwannomas: Case Series.

BACKGROUND: Schwannoma, a benign peripheral nerve sheath tumor, is perhaps only secondary to degenerative pathology as the most common lesion at neural foramen. The surgical dilemma here is either risking nerve injury because of inadequate exposure or the need for internal fixation because of facet joint sacrifice. OBJECTIVE: To evaluate the feasibility and safety of management of foraminal schwannomas by percutaneous full-endoscopic technique. METHODS: A single-center retrospective review was conducted on patients who underwent full-endoscopic resection of neural foraminal schwannomas. Tumors were grouped into either medial type or lateral type based on relevant location to the neural foramen, and respective surgical approaches were adopted. Data including preoperative neurological status, tumor size, surgery time, the extension of resection, and clinical outcomes were collected. The learning curve was plotted as surgical time/tumor size against case number. RESULTS: A total of 25 patients were treated between May 2015 and March 2022. Gross total resection was achieved in 24 patients, and near-total resection in 1 case, with 1 patient experienced transient voiding difficulty. No tumor recurrence or spinal instability was detected in the short-term follow-up (median follow-up 22 months, range 3 months-6 years). Surgical efficiency improved with the number of cases operated on and remained stable after the initial 10 cases. CONCLUSION: Percutaneous full-endoscopic technique is a safe and minimally invasive technique for the resection of foraminal schwannomas.

Qingyihuaji Formula promotes apoptosis and autophagy through inhibition of MAPK/ERK and PI3K/Akt/mTOR signaling pathway on pancreatic cancer in vivo and in vitro.

ETHNOPHARMACOLOGICAL RELEVANCE: Qingyihuaji Formula (QYHJ), a widely used traditional Chinese medicine (TCM), has been used to treat patients with cancer in China. However, the effect and mechanism of QYHJ on pancreatic ductal adenocarcinoma (PDAC) remains unclear. AIM OF THE STUDY: This study aimed to explore the roles and evaluate the possible underlying molecular mechanisms of QYHJ and its core component in PDAC using label-free quantitative proteomics in conjunction with network pharmacology-based analysis. MATERIALS AND METHODS: By screening differentially expressed proteins (DEPs) in proteomics and QYHJ-predicted gene sets, we identified QYHJ-related PDAC targets annotated with bioinformatic analysis. A subcutaneous tumor model was established to assess the role of QYHJ in vivo. The effects of quercetin (Que), a core component of QYHJ, on cell proliferation, migration, invasion, apoptosis, and autophagy in SW1990 and PANC-1 cells were investigated in vitro. Immunohistochemistry, western blotting, mRFP-GFP-LC3 adenovirus, and kinase analysis were used to determine the underlying mechanisms. RESULTS: Bioinformatics analysis revealed that 41 QYHJ-related PDAC targets were closely related to the cellular response to nitrogen compounds, positive regulation of cell death, regulation of epithelial cell apoptotic processes, and chemokine signaling pathways. CASP3, SRC, STAT1, PTPN11, PKM, and PAK1 with high expression were identified as hub DEPs in the PPI network, and these DEPs were associated with poor overall survival and STAT 1, MAPK/ERK, and PI3K/Akt/mTOR signaling pathways in PDAC patients. QYHJ significantly promoted tumor death in nude mice. Moreover, quercetin inhibited the proliferation, migration, and invasion of PDAC cells. Additionally, Que induced apoptosis and autophagy in PDAC cells. Mechanistically, QYHJ and Que significantly activated STAT 1 and remarkably inhibited the MAPK/ERK and PI3K/Akt/mTOR signaling pathways in vivo and in vitro, respectively. Importantly, ERK1/2 inactivation contributes to que-induced apoptosis in SW1990 and PANC-1 cells. CONCLUSIONS: These results suggest that QYHJ and Que are promising anti-PDAC avenues that benefit from their multiform mechanisms.

Spinal P2X4 Receptors Involved in Visceral Hypersensitivity of Neonatal Maternal Separation Rats.

Recent studies have demonstrated the vital role of P2X4 receptors (a family of ATP-gated non-selective cation channels) in the transmission of neuropathic and inflammatory pain. In this study, we investigated the role of spinal P2X4 receptors in chronic functional visceral hypersensitivity of neonatal maternal separation (NMS) rats. A rat model of irritable bowel syndrome was established by neonatal maternal separation. Visceral sensitivity was assessed by recording the response of the external oblique abdominal muscle to colorectal distension. P2X4 receptor antagonist and agonist were administrated intrathecally. The expression of P2X4 receptor was examined by Western Blot and immunofluorescence. The effect of P2X4 receptor antagonist on expression of brain-derived neurotrophic factor (BDNF) was assessed by Western Blot. We found neonatal maternal separation enhanced visceral hypersensitivity and increased the expression of P2X4 receptor in spinal thoracolumbar and lumbosacral segments of rats. Pharmacological results showed that visceral sensitivity was attenuated after intrathecal injection of P2X4 receptor antagonist, 5-BDBD, at doses of 10 nM or 100 nM, while visceral sensitivity was enhanced after intrathecal injection of P2X4 receptor agonist C5-TDS at doses of 10 µM or 15 µM. In addition, the spinal expression of BDNF significantly increased in NMS rats and intrathecal injection of 5-BDBD significantly decreased the expression of BDNF especially in NMS rats. C5-TDS failed to increase EMG amplitude in the presence of ANA-12 in control rats. Our results suggested the spinal P2X4 receptors played an important role in visceral hypersensitivity of NMS rats through BDNF.

Transcutaneous Electrical Acupoint Stimulation Combined with Warm Acupuncture for Breast Cancer Related Upper Limb Lymphedema: A Retrospective Cohort Study.

OBJECTIVE: To observe the clinical efficacy of transcutaneous electrical acupoint stimulation (TEAS) combined with warm acupuncture in treating breast cancer associated with upper limb lymphedema (BCRL). METHODS: This was a retrospective cohort study using a paired control design. Fifty-two BCRL patients were assigned to the control group (27 cases) and the treatment group (25 cases). The patients in the control group were treated with lymphedema comprehensive detumescence treatment (CDT) for 4 weeks, including systematic therapy composed of manual lymphatic drainage, compression bandage, skincare, and functional exercise. The patients in the treatment group were treated with TEAS combined with warm acupuncture based on the control group methods. Each treatment lasted for 30 min and was applied twice a week for 4 weeks. The arm circumference (AC) of different positions of the affected limb and the degree of swelling of the affected limb were evaluated before the first treatment and after the last treatment. The clinical efficacy was evaluated according to the degree of edema before and after treatment. All adverse events during treatment were recorded. RESULTS: The patients' AC and the swelling feeling of the affected limb in the treatment group and the control group were both reduced compared with those before treatment. Compared with the control group, AC of the wrist joint transverse stria, the midpoint between the wrist joint transverse stria and the elbow joint transverse stria in the treatment group were significantly reduced (P<0.05). The decrease in AC diameter at the midpoint between the elbow joint transverse stria and the axillary transverse stria was the most significant (P<0.01). The swelling degree of the affected limbs in the treatment group was significantly lower than before treatment, and was significantly lower compared with the control group after treatment (P<0.01). The total effective rate was 72% in the treatment group, significantly higher than that in the control group (55.56%, P<0.05). No serious adverse events occured in either group. CONCLUSIONS: TEAS combined with warm acupuncture can effectively reduce AC and swelling feeling of the affected limb in patients with BCRL. The effect is better than that of CDT therapy alone. (Registration No. ChiCTR2200062075).