The cellular and molecular basis of the spur development in Impatiens uliginosa.

The nectar spur is an important feature of pollination and ecological adaptation in flowering plants, and it is a key innovation to promote species diversity in certain plant lineages. The development mechanism of spurs varies among different plant taxa. As one of the largest angiosperm genera, we have little understanding of the mechanism of spur development in Impatiens. Here, we investigated the initiation and growth process of spurs of Impatiens uliginosa based on histology and hormone levels, and the roles of AUXIN BINDING PROTEIN (ABP) and extensin (EXT) in spur development were explored. Our results indicate that the spur development of I. uliginosa is composed of cell division and anisotropic cell elongation. Imbalances in spur proximal-distal cell division lead to the formation of curved structures. Endogenous hormones, such as auxin and cytokinins, were enriched at different developmental stages of spurs. IuABP knockdown led to an increase in spur curves and distortion of morphology. IuEXT knockdown resulted in reduced spur length and loss of curve and inner epidermal papillae structures. This study provides new insights into the mechanism of spur development in core eudicots.

Order-frequency Holo-Hilbert spectral analysis for machinery fault diagnosis under time-varying operating conditions.

Holo-Hilbert spectral analysis (HHSA) has been demonstrated to be an effective instantaneous feature demodulation tool for revealing the coupling relationship between the frequency-modulated (FM) carriers and amplitude-modulated (AM) characteristics within nonlinear and non-stationary mechanical vibration signals. However, it is unable to acquire the time varying AM characteristics from the vibration signals of the equipment operates under variable speed conditions. To decode such signals, inspired by HHSA, a novel angle-time double-layer decomposition structure termed order-frequency HHSA (OFHHSA) is established to demodulate the fault information from the time varying vibration signals in this paper. The corresponding spectrogram, namely, order-frequency Holo-Hilbert spectrum (OFHHS) is acquired for describing the interaction relationship between time and angle domains. Besides, the order AM-marginal spectrum is derived from the OFHHS via integrating the carrier variable to exhibit the fault characteristic-related orders. Moreover, the differences between OFHHSA and angle-time cyclo-stationary framework-based order-frequency spectral correlation (OFSC) are analyzed for time varying machinery fault diagnosis. Finally, from the analyses of simulated and tested data of mechanical equipment, the OFHHSA method has avoided the limitations of the two OFSC estimators on periodic assumption and the maximum cut-off order, and the proposed method obtained a more accurate rate in fault identification and more robust ability of anti-noise.

CD47-a novel prognostic predicator in epithelial ovarian cancer and correlations with clinicopathological and gene mutation features.

BACKGROUND: Epithelial ovarian cancer (EOC) is insensitive to immunotherapy due to its poor immunogenicity; thus, suitable biomarkers need to be identified for better prognostic stratification and individualized treatment. CD47 is a novel immunotherapy target; however, its impact on EOC prognosis is controversial and correlation with genetic features is unclear. The aim of this study was to investigate the prognostic significance of CD47 and its correlations with biological behaviors and genetic features of EOC. METHODS: Immunohistochemistry (IHC) and next-generation sequencing (NGS) were performed to examine expressions of CD47, PD-L1, and genomic mutations in the tissue samples of 75 EOC patients. Various clinicopathologic and genomic features were then evaluated to determine their correlation with CD47 expression. Kaplan-Meier analysis and Cox regression analysis were used to identify independent prognostic factors. Risk score modeling was then established, and the predictive capacity of this model was further confirmed by nomogram analysis. RESULTS: CD47 was mainly expressed in the tumor cell membrane and cytoplasm, and the rate of high CD47 expression was 63.7%. CD47 expression was associated with various clinicopathological factors, including FIGO stage, CA125 and HE4 value, presence of multidisciplinary surgeries, presence and volume of ascites, lymph-node metastasis, Ki-67 index and platinum-resistant, as well as genetic characteristics like BRCA mutation, HRD status, and TP53 mutation in EOC. Patients with high CD47 expression showed worse prognosis than the low-expression group. Cox regression analysis demonstrated that CA125, CD47, and BRCA mutation were independent factors for EOC prognosis. Patients were then categorized into high-risk and low-risk subgroups based on the risk score of the aforementioned independent factors, and the prognosis of the high-risk group was worse than those of the low-risk group. The nomogram showed adequate discrimination with a concordance index of 0.777 (95% CI, 0.732-0.822). The calibration curve showed good consistency. CONCLUSION: CD47 correlated with various malignant biology and genetic characteristics of EOC and may play pivotal and multifaceted roles in the tumor microenvironment of EOC Finally, we constructed a reliable prediction model centered on CD47 and integrated CA125 and BRCA to better guide high-risk population management.

A Fetus with Maternal Uniparental Disomy on Chromosome 20: Case Report with Genetic Analysis and Prenatal Diagnosis.

BACKGROUND: A fetus with increased copy number of chromosome 20 was identified by NIPT. Here we utilize several genetic tests and analyses to illuminate the etiology of such aneuploidy. METHODS: Amniotic fluid cells were extracted from pregnant woman and sent for karyotype and chromosomal microarray analysis (CMA). Trio pedigree analysis was conducted with Chromosome Analysis Suite and uniparental disomy (UPD)-tool software. RESULTS: CMA identified consistent results, which were 2 regions of homozygosity: arr[GRCh37]20p12.2q11.1 (11265096_26266313)hmz and arr[GRCh37]20q11.21q13.2(29510306_54430467)hmz. The trio pedigree analysis discovered that the fetal chromosome 20 was the entire maternal UPD mosaic with isodisomy and heterodisomy. CONCLUSIONS: When a large segment of chromosome is homozygous, appropriate genetic tests are required to find the potential mechanisms for UPD formation.

Novel predictors for identifying cervical minimal deviation adenocarcinoma patients with poor prognosis: a long-term observational study in a tertiary centre.

PURPOSE: To elucidate the clinicopathological features and prognostic factors of minimal deviation adenocarcinoma (MDA) of the uterine cervix, a clinically rare but highly invasive disease. METHODS: This was a retrospective, observational, real-world study of 43 patients with pathologically confirmed MDA at the Obstetrics and Gynaecology Hospital of Fudan University between November 2010 and November 2021. Baseline clinicopathological data were collected and reviewed. Prognostic factors for progression-free survival (PFS) and overall survival (OS) were investigated by univariate and multivariate Cox proportional hazards analyses. RESULTS: Chief complaints included irregular vaginal discharge and/or bleeding (74.4%). Preoperative diagnosis was difficult, the detection rate was low (36.8%), all cases showed endophytic lesions, and 88.4% had deep stromal invasion, with biologically aggressive characteristics. The ovarian metastasis rate was high (16.3%, 7/43). The median maximum diameter of the tumour (MDOT) was 4.3 cm (range, 0.5-8.0 cm). MDOT was significantly associated with OS (P = 0.009), and the optimal cut-off value to define bulky MDA was 5.5 cm (P < 0.0001, χ= 21.161) using X-tile software. Independent prognostic factors included MDOT (HR = 10.095, P = 0.001) and ovarian metastasis (HR = 5.888, P = 0.008) for OS and MDOT (HR = 3.944, P = 0.028), ovarian metastasis (HR = 9.285, P = 0.001), and deep infiltration (HR = 3.627, P = 0.048) for PFS. CONCLUSION: Endophytic lesion development and ovarian metastasis are likely in MDA. A bulky tumour and ovarian metastasis indicate a worse prognosis. Given the special biological features of MDA, it is more appropriate to use 5.5 cm as the threshold for defining a bulky tumour than it is to use 4 cm. Ovary removal should be given higher priority to improve prognosis.

Protective Effects of Danmu Extract Syrup on Acute Lung Injury Induced by Lipopolysaccharide in Mice through Endothelial Barrier Repair / 中国结合医学杂志

OBJECTIVE@#To investigate the effects of Danmu Extract Syrup (DMS) on lipopolysaccharide (LPS)-induced acute lung injury (ALI) in mice and explore the mechanism.@*METHODS@#Seventy-two male Balb/C mice were randomly divided into 6 groups according to a random number table (n=12), including control (normal saline), LPS (5 mg/kg), LPS+DMS 2.5 mL/kg, LPS+DMS 5 mL/kg, LPS+DMS 10 mL/kg, and LPS+Dexamethasone (DXM, 5 mg/kg) groups. After pretreatment with DMS and DXM, the ALI mice model was induced by LPS, and the bronchoalveolar lavage fluid (BALF) were collected to determine protein concentration, cell counts and inflammatory cytokines. The lung tissues of mice were stained with hematoxylin-eosin, and the wet/dry weight ratio (W/D) of lung tissue was calculated. The levels of tumor necrosis factor-α (TNF-α), interleukin (IL)-6 and IL-1 β in BALF of mice were detected by enzyme linked immunosorbent assay. The expression levels of Claudin-5, vascular endothelial (VE)-cadherin, vascular endothelial growth factor (VEGF), phospho-protein kinase B (p-Akt) and Akt were detected by Western blot analysis.@*RESULTS@#DMS pre-treatment significantly ameliorated lung histopathological changes. Compared with the LPS group, the W/D ratio and protein contents in BALF were obviously reduced after DMS pretreatment (P<0.05 or P<0.01). The number of cells in BALF and myeloperoxidase (MPO) activity decreased significantly after DMS pretreatment (P<0.05 or P<0.01). DMS pre-treatment decreased the levels of TNF-α, IL-6 and IL-1 β (P<0.01). Meanwhile, DMS activated the phosphoinositide 3-kinase/protein kinase B (PI3K/Akt) pathway and reversed the expressions of Claudin-5, VE-cadherin and VEGF (P<0.01).@*CONCLUSIONS@#DMS attenuated LPS-induced ALI in mice through repairing endothelial barrier. It might be a potential therapeutic drug for LPS-induced lung injury.

Research progress on commonly used visual acuity charts for preschool children / 国际眼科杂志(Guoji Yanke Zazhi)

Preschool age(3-6 years old)is a critical period for visual development, and it is crucial to detect and treat visual problems in preschool children as early as possible. Visual acuity charts are important tools for screening visual issues in children. In China, the commonly used charts are the standard logarithmic visual acuity chart and the pediatric optotype chart, while overseas, the Lea, HOTV, and ETDRS visual acuity charts are frequently employed. Numerous studies have reported the measurability, repeatability, and sensitivity of these three charts in diagnosing visual-related problems in children. However, the application of these three charts is relatively limited in China. This article provides a comprehensive review of the design principles, clinical applications, and characteristics of these three visual acuity charts, so as to better understand their applicability and limitations in preschool children, and provide reference for the selection and improvement of vision examination methods in the future.

Survival after induction chemotherapy in locoregional advanced nasopharyngeal carcinoma: An updated systematic review and meta-analysis.

Background: Induction chemotherapy (ICT) augmentation is a common strategy for standard concurrent chemoradiotherapy (CCRT) of locoregionally advanced nasopharyngeal carcinoma (NPC). The survival condition is a crucial issue for patients with locoregionally advanced NPC. The survival of ICT patients with CCRT treatment versus standard CCRT alone should be elucidated via a systemic review and meta-analysis of randomized clinical trials. Methods: We compared ICT with CCRT and CCRT alone treatment to determine if ICT with CCRT can be associated with a significant benefit of survival conditions versus CCRT. Different survival indicators were analyzed for the ICT with CCRT. Twelve studies with a total of 3711 patients with locoregionally advanced NPC were enrolled. The focused outcome was the overall survival, progression-free survival, distant metastasis-free survival, and locoregional recurrence-free survival. Results: Our results showed that ICT with CCRT is associated with a significant benefit for the overall survival status versus CCRT treatment. Similar significant benefits in the survival condition were seen in progression-free survival, distant metastasis-free survival, and locoregional recurrence-free survival. Conclusions: The updated meta-analysis results suggest that the ICT with CCRT might be associated with significant benefits of survival in overall, progression-free, distant metastasis-free, as well as locoregional recurrence-free dimensions versus CCRT treatment. However, the bias of different kinds, doses, and regimens of chemotherapy agents and radiotherapy should not be ignored.

Association of clinical characteristics and recurrence of conventional colorectal adenomas with patient age: a single-center study.

OBJECTIVES: We performed a clinical study comparing early-onset and late-onset conventional colorectal adenomas (CCRAs) since little is known about the differences in their characteristics. METHODS: Pearson's chi-square test and the Kruskal‒Wallis test were used to compare basic information. MCAR tests and multiple imputation were performed to complete missing values. Multivariate logistic analysis and propensity score matching were used to identify the risk factors for recurrence. RESULTS: We included 2793 patients (688 with early-onset CCRAs and 2105 with late-onset CCRAs) from January 2017 to December 2021. Patients with early-onset CCRAs had higher levels of Hb, ALB, and triglycerides but lower HDL levels and N/L ratios. Moreover, we found that more early-onset CCRAs were in the left colon than late-onset CCRAs, and the size of early-onset CCRAs was larger. Early-onset CCRAs tended to lack pedicles compared to late-onset CCRAs. Additionally, the ratio of EMR and APC in early-onset CCRAs was higher than that in late-onset CCRAs, and the ratio of ESD and surgery for late-onset CCRAs was higher. We found that age ≥ 50 years, abnormal vessels, drinking alcohol, and DB and ALB levels may be risk factors for recurrence, while the LDL level may be a protective factor. Finally, analysis of cumulative recurrence rates after PSM showed that patients with late-onset CCRAs exhibited higher recurrence rates (P < 0.05). CONCLUSION: Compared with late-onset CCRAs, early-onset CCRAs were associated with higher triglyceride levels, lower HDL levels, and larger tumor volumes. Age ≥ 50 years, abnormal vessels, alcohol consumption, and DB and ALB levels were independent risk factors for recurrence of CCRAs.

Methods of postoperative void trial management after urogynecologic surgery: a systematic review and meta-analysis.

BACKGROUND: Voiding trials are used to identify women at risk for postoperative urinary retention while performing optimal voiding trial management with minimal burden to the patient and medical service team. We performed a systematic review and meta-analysis of postoperative void trials following urogynecologic surgery to investigate (1) the optimal postoperative void trial methodology and (2) the optimal criteria for assessing void trial. METHOD: We searched PubMed, EMBASE, Cochrane Central Register of Controlled Trials, and relevant reference lists of eligible articles from inception to April 2022. We identified any randomized controlled trials (RCTs) in English that studied void trials in patients undergoing urogynecologic surgery. Study selection (title/abstract and full text), data extraction, and risk of bias assessment were conducted by two independent reviewers. Extracted study outcomes included the following: the correct passing rate, time to discharge, discharge rate without a catheter after the initial void trial, postoperative urinary tract infection, and patient satisfaction. RESULTS: Void trial methodology included backfill-assisted and autofill studies (2 RCTs, n = 95). Backfill assistance was more likely to be successful than autofill (RR 2.12, 95% CI 1.29, 3.47, P = 0.00); however, no significant difference was found in the time to discharge (WMDs = - 29.11 min, 95% CI - 57.45, 1.23, P = 0.06). The criteria for passing void trial included subjective assessment of the urinary force of stream and objective assessment of the standard voiding trial (3 RCTs, n = 377). No significant differences were found in the correct passing rate (RR 0.97, 95% CI 0.93, 1.01, P = 0.14) or void trial failure rate (RR 0.78, 95% CI 0.52, 1.18, P = 0.24). Moreover, no significant differences were found in the complication rates or patient satisfaction between the two criteria. CONCLUSION: Bladder backfilling was associated with a lower rate of catheter discharge after urogynecologic surgery. The subjective assessment of FOS is a reliable and safe method for assessing postoperative voiding because it is less invasive. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42022313397.

Do ethnic chinese older adults with epithelial ovarian cancer survive a poorer prognosis?

BACKGROUND: The risk of suffering epithelial ovarian cancer (EOC) for women increases with age evidently, while the prognosis of older EOC patients remain unclear. Against the backdrop of the accelerate aging process in China, this paper investigates whether the older EOC patients have a lower overall survival probability than the younger patients based on the sample of ethnic Chinese population. METHODS: A total of 323 ethnic Chinese patients diagnosed as epithelial ovarian cancer were extracted from the Surveillance, Epidemiology, and End Results (SEER) database. We compared the overall survival probability between the younger group (< 70 years) and the older patients group (≥ 70 years). Survival curves were drawn using the Kaplan-Meier method, comparisons among different subgroups were evaluated using log-rank tests, and independent prognostic factors were identified by univariate and multivariate Cox regression analyses. RESULTS: 43 patients were (13.3%) in the older patients group and 280 (86.7%) in the younger group. The distribution patterns between two groups were significantly different with regard to marital status, histologic type and FIGO stage. The median overall survival (OS) was significantly longer in the younger group than the older patients group (not reached vs. median 39 months, p < 0.05). The multivariate analysis demonstrated that the age (The older vs. the younger, HR: 1.967, P = 0.007), primary tumor laterality (HR: 1.849, P = 0.009), and FIGO stage (III vs. I, HR: 3.588, P = 0.001; and IV vs. I, HR: 4.382, P = 0.001; respectively) remained as important risk factors while Histology (HGSOC vs. CCOC, HR: 0.479, P = 0.025; and LGSOC/MOC/EC vs. CCOC, HR: 0.390, P = 0.034; respectively) and the number of lymph node dissected more than 10 was a protective factor (HR: 0.397, P = 0.008). In an analysis of 104 pairs of patients matched on the basis of the propensity score, the older patients group had significantly lower overall mortality (HR = 2.561, P = 0.002). CONCLUSION: Ethnic Chinese Older EOC patients have a worse prognosis than the younger patients.

Ultrasonic-assisted binding of canistel (Lucuma nervosa A.DC) seed starch with quercetin.

In order to provide a reference for improving the physicochemical properties of starch, the study of starch polyphenol complex interaction has aroused considerable interest. As a common method of starch modification, ultrasound can make starch granules have voids and cracks, and make starch and polyphenols combine more closely. In this research, canistel seed starch was modified by ultrasonic treatment alone or combined with quercetin. The molecular structure, particle characteristics and properties of starch were evaluated. With the increase of ultrasonic temperature, the particle size of the dextrinized starch granules increased, but the addition of quercetin could protect the destruction of starch granule size by ultrasonic; X-ray diffraction and infrared spectra indicated that quercetin was bound to the surface of canistel seed starch through hydrogen bonding, and the complex and the original starch had the same crystal structure and increased crystallinity; by molecular simulation, quercetin bound inside the starch molecular helix preserved the crystalline helical configuration of starch to some extent and inhibited the complete unhelicalization of starch molecules. Meanwhile, hydrogen bonding was the main driving force for the binding of starch molecules to quercetin, and van der Waals interactions also promoted the binding of both. In the physicochemical properties, as the temperature increased after the combination of ultrasonic modified starch combined with quercetin, the solubility, swelling force and apparent viscosity of the compound increased significantly, and it has higher stability and shear resistance.

A population-based characterization study of anti-mitochondrial M2 antibodies and its consistency with anti-mitochondrial antibodies.

OBJECTIVE: This study aims to estimate the prevalence of anti-mitochondrial antibody subtype M2 (AMA-M2) and assess its consistency with AMA in a general population. METHODS: A total of 8954 volunteers were included to screen AMA-M2 using enzyme-linked immunosorbent assay. Sera with AMA-M2 >50 RU/mL were further tested for AMA using an indirect immunofluorescence assay. RESULTS: The population frequency of AMA-M2 positivity was 9.67%, of which 48.04% were males and 51.96% were females. The AMA-M2 positivity in males had a peak and valley value of 7.81% and 16.88% in those aged 40 to 49 and ≥70 years, respectively, whereas it showed a balanced age distribution in females. Transferrin and immunoglobulin M were the risk factors for AMA-M2 positivity and exercise was the only protective factor. Of 155 cases with AMA-M2 >50 RU/mL, 25 cases were AMA-positive, with a female-to-male ratio of 5.25:1. Only 2 people, with very high AMA-M2 of 760 and >800 RU/mL, met the diagnostic criteria of primary biliary cholangitis (PBC), making the prevalence of PBC 223.36 per million in southern China. CONCLUSION: We found that AMA-M2 has a low coincidence rate with AMA in the general population. A new decision-making point for AMA-M2 is needed to improve consistency with AMA and diagnostic accuracy.

Characteristic mango price forecasting using combined deep-learning optimization model.

Accurate product price forecasting is helpful for scientific decision-making and precise industrial planning. As a characteristic fruit that drives regional development, mango price prediction is of great significance to several economies. However, owing to the strong volatility of mango prices, forecasting is vulnerable to uncertainties and is very challenging. In this study, a deep-learning combination forecasting model based on a back-propagation (BP) long short-term memory (LSTM) neural network is proposed. Using daily mango price data from a large fruit wholesale trading center in China from January 2nd, 2014, to April 18th, 2022, mango price changes are learned and predicted to support the fruit industry. The results show that the root mean-square error, mean absolute percentage error, and the R2 determination coefficient of the BP-LSTM combination model are 0.0175, 0.14%, and 0.9998, respectively. The prediction results of the combined model are better than those of the separate BP and LSTM models. Furthermore, it best fits the actual price profile and has better generalizability.

How enterprise interactions in innovation networks affect technological innovation performance: The role of technological innovation capacity and absorptive capacity.

Current research on the impact of innovation networks focuses on the web and inter-organizational layers, with less consideration of individual behavior at the firm level. Interaction is an active action strategy that firms take when dealing with the external environment. Therefore, this study explores the mechanism of enterprise interaction on innovation development from the perspective of an innovation network. And measures enterprise interaction in three dimensions: affective interaction, resource interaction, and management interaction. The empirical results indicate that the three dimensions of enterprise interaction contribute significantly to technological innovation performance, and the realization of this role requires technological innovation capabilities (technological research and development capabilities, technological commercialization capabilities) to play a partially mediating role. The moderating effect of absorptive capacity between resource interaction, management interaction, and technological innovation capability is significant; however, the moderating effect between affective interaction and technological innovation capability is statistically insignificant. This study promotes the development of interaction theory to a certain extent, which helps enterprises build appropriate industrial chains in innovation networks and achieve rapid development.

Determining the changes in metabolites of Dendrobium officinale juice fermented with starter cultures containing Saccharomycopsis fibuligera FBKL2.8DCJS1 and Lactobacillus paracasei FBKL1.3028 through untargeted metabolomics.

BACKGROUND: The present study aimed to investigate the changes in volatile components and metabolites of Dendrobium officinale (D. officinale) juice fermented with starter cultures containing Saccharomycopsis fibuligera and Lactobacillus paracasei at 28 ℃ for 15 days and post-ripened at 4 ℃ for 30 days using untargeted metabolomics of liquid chromatography-mass spectrometry (LC-MS) and headspace solid-phase microextraction-gas chromatography (HS-SPME-GC-MS) before and after fermentation. RESULTS: The results showed that the alcohol contents in the S. fibuligera group before fermentation and after fermentation were 444.806 ± 10.310 µg/mL and 510.999 ± 38.431 µg/mL, respectively. Furthermore, the alcohol content in the fermentation broth group inoculated with the co-culture of L. paracasei + S. fibuligera was 504.758 ± 77.914 µg/mL, containing a significant amount of 3-Methyl-1-butanol, Linalool, Phenylethyl alcohol, and 2-Methyl-1-propanol. Moreover, the Ethyl L (-)-lactate content was higher in the co-culture of L. paracasei + S. fibuligera group (7.718 ± 6.668 µg/mL) than in the L. paracasei (2.798 ± 0.443 µg/mL) and S. fibuligera monoculture groups (0 µg/mL). The co-culture of L. paracasei + S. fibuligera significantly promoted the metabolic production of ethyl L (-)-lactate in D. officinale juice. The differential metabolites screened after fermentation mainly included alcohols, organic acids, amino acids, nucleic acids, and their derivatives. Twenty-three metabolites, including 11 types of acids, were significantly up-regulated in the ten key metabolic pathways of the co-culture group. Furthermore, the metabolic pathways, such as pentose and glucuronate interconversions, the biosynthesis of alkaloids derived from terpenoid and polyketide, and aminobenzoate degradation were significantly up-regulated in the co-culture group. These three metabolic pathways facilitate the synthesis of bioactive substances, such as terpenoids, polyketides, and phenols, and enrich the flavor composition of D. officinale juice. CONCLUSIONS: These results demonstrate that the co-culture of L. paracasei + S. fibuligera can promote the flavor harmonization of fermented products. Therefore, this study provides a theoretical basis for analyzing the flavor of D. officinale juice and the functional investigation of fermentation metabolites.

Dipyridamole enhances the anti-cancer ability of aspirin against colorectal cancer by inducing apoptosis in an unfolded protein response-dependent manner.

PURPOSE: Available evidence indicates that dipyridamole enhances the anti-thrombotic effects of aspirin for the prevention of secondary strokes. Aspirin is a well-known non-steroid anti-inflammatory drug. This anti-inflammatory property has turned aspirin into a potential drug for inflammation-related cancers such as colorectal cancer (CRC). Here, we aimed to explore whether the anti-cancer effect of aspirin against CRC could be improved by combined administration with dipyridamole. METHODS: Population-based clinical data analysis was conducted to assess a possible therapeutic effect of combined dipyridamole and aspirin treatment in inhibiting CRC compared with either monotherapy. This therapeutic effect was further verified in different CRC mouse models, i.e. an orthotopic xenograft mouse model, an AOM/DSS mouse model, an Apcmin/+ mouse model and a patient derived xenograft (PDX) mouse model. The in vitro effects of the drugs on CRC cells were tested using CCK8 and flow cytometry assays. RNA-Seq, Western blotting, qRT-PCR and flow cytometry were used to identify the underlying molecular mechanisms. RESULTS: We found that dipyridamole combined with aspirin had a better inhibitory effect on CRC than either monotherapy alone. The enhanced anti-cancer effect of the combined use of dipyridamole with aspirin was found to rely on the induction of an overwhelmed endoplasmic reticulum (ER) stress and subsequent pro-apoptotic unfolded protein response (UPR), which was different from the anti-platelet effect. CONCLUSIONS: Our data indicate that the anti-cancer effect of aspirin against CRC may be enhanced by combined administration with dipyridamole. In case further clinical studies confirm our findings, these may be repurposed as adjuvant agents.

Effect of trigger point acupuncture on pain and functional activity in patients with chronic non-specific low back pain: a randomised controlled trial.

BACKGROUND: Trigger point (TrP) acupuncture is commonly used to treat chronic non-specific low back pain (CNLBP). Evidence for the efficacy of most TrP acupuncture modalities is weak or lacking. OBJECTIVE: To assess the effect of TrP acupuncture on pain, disability, gait and muscle activation in patients with CNLBP. METHODS: From May 2019 to February 2020, a randomised, single-blind clinical trial was carried out involving 33 participants with CNLBP, divided into one of two intervention groups or a control group (n = 11 per group). The intervention groups received TrP acupuncture or traditional acupuncture treatment three times a week for 4 weeks, and the control group remained on a waiting list and received no treatment. Pain, disability, gait and muscle activation were assessed at baseline and at 4 and 8 weeks of follow-up. RESULTS: At baseline, the three groups showed no significant differences in age, gender, height, weight, body mass index (BMI) or disease course (p ⩾ 0.05). At 4 weeks, pain was relieved (measured by visual analogue scores, p = 0.036) and disability was improved (reflected by lower Oswestry disability index scores, p = 0.029) in TrP acupuncture versus waiting list groups. Moreover, lumbar extension range of motion was increased in TrP acupuncture versus both traditional acupuncture and waiting list groups (p = 0.029 and p = 0.027, respectively). At 8 weeks, there were no significant differences in any parameter between the three groups (p > 0.05). CONCLUSION: TrP acupuncture had a significant short-term effect on pain relief and disability in patients with CNLBP, but there was no evidence of a long-term influence (at 8 weeks following the intervention). Further high-quality randomised controlled trials are needed for verification in the future.Trial registration number: ChiCTR1900022838 (Chinese Clinical Trial Registry).

Blocking CD47-SIRPα Signal Axis as Promising Immunotherapy in Ovarian Cancer.

Among the three primary gynecological malignancies, ovarian cancer has the lowest incidence but the worst prognosis. Because of the poor prognosis of ovarian cancer patients treated with existing treatments, immunotherapy is emerging as a potentially ideal alternative to surgery, chemotherapy, and targeted therapy. Among immunotherapies, immune checkpoint inhibitors have been the most thoroughly studied, and many drugs have been successfully used in the clinic. CD47, a novel immune checkpoint, provides insights into ovarian cancer immunotherapy. This review highlights the mechanisms of tumor immune evasion via CD47-mediated inhibition of phagocytosis and provides a comprehensive insight into the progress of the relevant targeted agents in ovarian cancer.