The interaction of platelet-related factors with tumor cells promotes tumor metastasis.

Platelets not only participate in thrombosis and hemostasis but also interact with tumor cells and protect them from mechanical damage caused by hemodynamic shear stress and natural killer cell lysis, thereby promoting their colonization and metastasis to distant organs. Platelets can affect the tumor microenvironment via interactions between platelet-related factors and tumor cells. Metastasis is a key event in cancer-related death and is associated with platelet-related factors in lung, breast, and colorectal cancers. Although the factors that promote platelet expression vary slightly in terms of their type and mode of action, they all contribute to the overall process. Recognizing the correlation and mechanisms between these factors is crucial for studying the colonization of distant target organs and developing targeted therapies for these three types of tumors. This paper reviews studies on major platelet-related factors closely associated with metastasis in lung, breast, and colorectal cancers.

A review of platelet-rich plasma for enteric fistula management.

Enteric fistula (EF), a serious complication after abdominal surgery, refers to unnatural communication between the gastrointestinal tract and the skin or other hollow organs. It is associated with infection, massive fluid/electrolyte loss, and malnutrition, resulting in an unhealed course. Despite advances in surgical techniques, wound care, infection control, and nutritional support, EF remains associated with considerable morbidity and mortality. Autologous platelet-rich plasma (PRP) containing elevated platelet concentrations has been proposed to promote healing in many tissues. However, the mechanism of action of PRP in EF treatment remains unclear owing to its complicated clinical manifestations. In this review, we summarized the clinical approaches, outlined the principal cytokines involved in the healing effects, and discussed the advantages of PRP for EF therapy. In addition, we defined the mechanism of autologous PRP in EF management, which is essential for further developing EF therapies.

Vanillic acid alleviates liver fibrosis through inhibiting autophagy in hepatic stellate cells via the MIF/CD74 signaling pathway.

MIF/CD74 signaling pathway and autophagy may be closely related to liver fibrosis. Vanillic acid (VA) is likely to have an anti-liver fibrosis effect, although related studies have not been reported. The aim of this study was to verify the role of hepatic stellate cells (HSCs) autophagy and the MIF/CD74 signaling pathway in the pathogenesis of liver fibrosis, and to investigate the effect of VA on liver fibrosis through in vivo and in vitro experiments. Our results showed that VA significantly attenuated CCl4-induced liver fibrosis. The alleviation of liver fibrosis with VA treatment was associated with a reduction of MIF, CD74, α-SMA, LC3B and Collagen 1. In addition, VA, MIF inhibitor (ISO-1) and autophagy inhibitor (3-MA) markedly inhibited the proliferation and migration of HSCs. This study indicates that VA could protect against HSCs activation, proliferation and migration by inhibiting the autophagy in HSCs via the MIF/CD74 signaling pathway so that alleviates liver fibrosis.

Nonlinearity synergy: An elegant strategy for realizing high-sensitivity and wide-linear-range pressure sensing.

Flexible pressure sensors are indispensable components in various applications such as intelligent robots and wearable devices, whereas developing flexible pressure sensors with both high sensitivity and wide linear range remains a great challenge. Here, we present an elegant strategy to address this challenge by taking advantage of a pyramidal carbon foam array as the sensing layer and an elastomer spacer as the stiffness regulator, realizing an unprecedentedly high sensitivity of 24.6 kPa-1 and an ultra-wide linear range of 1.4 MPa together. Such a wide range of linearity is attributed to the synergy between the nonlinear piezoresistivity of the sensing layer and the nonlinear elasticity of the stiffness regulator. The great application potential of our sensor in robotic manipulation, healthcare monitoring, and human-machine interface is demonstrated. Our design strategy can be extended to the other types of flexible sensors calling for both high sensitivity and wide-range linearity, facilitating the development of high-performance flexible pressure sensors for intelligent robotics and wearable devices.

Investigation of a Novel Ultra-Low-Frequency Rotational Energy Harvester Based on a Double-Frequency Up-Conversion Mechanism.

Due to their lack of pollution and long replacement cycles, piezoelectric energy harvesters have gained increasing attention as emerging power generation devices. However, achieving effective energy harvesting in ultra-low-frequency (<1 Hz) rotational environments remains a challenge. Therefore, a novel rotational energy harvester (REH) with a double-frequency up-conversion mechanism was proposed in this study. It consisted of a hollow cylindrical shell with multiple piezoelectric beams and a ring-shaped slider with multiple paddles. During operation, the relative rotation between the slider and the shell induced the paddles on the slider to strike the piezoelectric beams inside the shell, thereby causing the piezoelectric beams to undergo self-excited oscillation and converting mechanical energy into electrical energy through the piezoelectric effect. Additionally, by adjusting the number of paddles and piezoelectric beams, the frequency of the piezoelectric beam struck by the paddles within one rotation cycle could be increased, further enhancing the output performance of the REH. To validate the output performance of the proposed REH, a prototype was fabricated, and the relationship between the device's output performance and parameters such as the number of paddles, system rotation speed, and device installation eccentricity was studied. The results showed that the designed REH achieved a single piezoelectric beam output power of up to 2.268 mW, while the REH with three piezoelectric beams reached an output power of 5.392 mW, with a high power density of 4.02 µW/(cm3 Hz) under a rotational excitation of 0.42 Hz, demonstrating excellent energy-harvesting characteristics.

Near-infrared fluorophore IR-61 delays postovulatory aging of mouse oocytes through suppressing oxidative stress mediated by mitochondrial protection.

Postovulatory aging can trigger deterioration of oocyte quality and subsequent embryonic development, and thus reduce the success rates of assisted reproductive technology (ART). The molecular mechanisms underlying postovulatory aging, and preventative strategies, remain to be explored. The near-infrared fluorophore IR-61, a novel heptamethine cyanine dye, has the potential for mitochondrial targeting and cell protection. In this study, we found that IR-61 accumulated in oocyte mitochondria and reduced the postovulatory aging-induced decline in mitochondrial function, including mitochondrial distribution, membrane potential, mtDNA number, ATP levels, and mitochondrial ultrastructure. In addition, IR-61 rescued postovulatory aging-caused oocyte fragmentation, defects in spindle structure, and embryonic developmental potential. RNA sequencing analysis indicated that the postovulatory aging-induced oxidative stress pathway might be inhibited by IR-61. We then confirmed that IR-61 decreased the levels of reactive oxygen species and MitoSOX, and increased GSH content in aged oocytes. Collectively, the results indicate that IR-61 may prevent postovulatory aging by rescuing oocyte quality, promoting successful rate in ART procedure.

Effects of the interactions between platelets with other cells in tumor growth and progression.

It has been confirmed that platelets play a key role in tumorigenesis. Tumor-activated platelets can recruit blood cells and immune cells to migrate, establish an inflammatory tumor microenvironment at the sites of primary and metastatic tumors. On the other hand, they can also promote the differentiation of mesenchymal cells, which can accelerate the proliferation, genesis and migration of blood vessels. The role of platelets in tumors has been well studied. However, a growing number of studies suggest that interactions between platelets and immune cells (e.g., dendritic cells, natural killer cells, monocytes, and red blood cells) also play an important role in tumorigenesis and tumor development. In this review, we summarize the major cells that are closely associated with platelets and discuss the essential role of the interaction between platelets with these cells in tumorigenesis and tumor development.

Autologous platelet-rich plasma for the treatment of nonhealing perineal wounds: a report of two cases.

INTRODUCTION: Patients with perineal wounds often encounter difficulty in local wound healing after hemorrhoidectomies. PRP contains a high concentration of platelets and has been used to improve wound healing. OBJECTIVE: In this case study, PRP was used in the treatment of nonhealing perineal wounds to expedite wound healing. CASE REPORTS: The 2 patients in these cases suffered from perineal wounds that were nonhealing for more than 2 months. After assessment of their physical condition, autologous PRP was used in the treatment of both patients. A total of 150 mL of peripheral blood was collected from each patient to prepare autologous PRP in a completely enclosed environment. For one patient, the PRP product was injected subcutaneously around the wound. The rest of the PRP product was activated into a gel by thrombin and calcium chloride, and the gel was applied to the surface of the wound with dressing changes every 5 days. The other patient was externally treated with autologous PRP gel, and dressing changes were administered after a week. The 2 patients were treated twice with PRP, and both completely recovered within 2 weeks without any other treatment. CONCLUSION: As an autologous blood-derived product, PRP was safe and showed promising results in perineal wound healing.

Near-infrared fluorophore IR-61 improves the quality of oocytes in aged mice via mitochondrial protection.

Maternal aging is associated with a decline in oocyte quality, which leads to the decreased fertility. Therefore, developing approaches to reduce aging-induced deterioration of oocyte quality in older women is important. Near-infrared cell protector-61 (IR-61), a novel heptamethine cyanine dye, has the potential for antioxidant effects. In this study, we found that IR-61 can accumulate in the ovaries and improved ovarian function of naturally aged mice; it also increased the oocyte maturation rate and quality by maintaining the integrity of the spindle/chromosomal structure and reducing the aneuploidy rate. In addition, the embryonic developmental competence of aged oocytes was improved. Finally, RNA-sequencing analysis indicated that IR-61 might perform the beneficial effects on aged oocytes by regulating mitochondrial function, this was confirmed by immunofluorescence analysis of mitochondrial distribution and reactive oxygen species. Taken together, our findings demonstrate that IR-61 supplementation in vivo can increase oocyte quality and protect oocytes from aging-induced mitochondrial dysfunction, and thus could improve the fertility of older women and efficiency of assisted reproductive technology.

Design and Experimental Investigation of an Ultra-Low Frequency, Low-Intensity, and Multidirectional Piezoelectric Energy Harvester with Liquid as the Energy-Capture Medium.

Traditional piezoelectric vibration energy harvesters (PVEHs) usually adopt a rigid energy-capture structure, which can achieve efficient energy harvesting in single-directional, high-frequency, and high-intensity vibration environments. However, efficient harvesting with the use of low-frequency, low-intensity, and multidirectional vibration energy remains a challenge for existing harvesters. To tackle this problem, we proposed a PVEH with liquid as the energy-capture medium. Our previous research verified that this set up can show a good energy harvesting performance under low-frequency, low-intensity, and horizontal multidirectional vibration excitation. In this paper, we further studied the possibility of vertical multidirectional energy harvesting using this device, as well as the influence of several important parameters (rope margin, liquid level height, and floating block shape) on the output performance. The results showed that the proposed PVEH can realize energy harvesting in three-dimensional space and that the output characteristic is adjustable.

Efficacy and safety of docetaxel plus S-1-based therapy in gastric cancer: a quantitative evidence synthesis of randomized controlled trials.

Objective: To systematically evaluate the safety and efficacy of docetaxel plus S-1-based therapy in gastric cancer treatment. Methods: PubMed, Embase, The Cochrane Library, and Web of Science electronic databases were searched for randomized controlled trials on docetaxel plus S-1-based therapy in the treatment of gastric cancer from the establishment of the database to 1 September 2022. Relevant studies were included per pre-defined eligibility criteria, and two researchers independently screened and assessed the included literature using Review Manager v5. Outcome measures and statistics related with efficacy and safety profiles were extracted from the included studies, and Stata v15.1 was used for pooled analysis. Results: Objective response rate (odds ratio = 2.34, 95% CI = [1.32, 4.13], p = 0.003), relapse-free survival (HR = 0.68, 95% CI = [0.58, 0.79], p < 0.001), progression-free survival (HR = 0.81, 95% CI = [0.68, 0.96], p = 0.016), and overall survival (HR = 0.86, 95% CI = [0.79, 0.95], p = 0.002) of docetaxel plus S-1-based therapy (DS-based therapy) in gastric cancer treatment were better than those of the non-DS-based therapy. However, DS-based therapy was associated with increased risk of certain adverse drug effects, such as alopecia, leukopenia, and oral mucositis. Further studies are warranted to validate the efficacy superiority of DS-based versus non-DS-based regimens as per our trial sequential analysis findings. Conclusion: DS-based therapy significantly improves patients' clinical outcomes in gastric cancer, albeit at the cost of increased toxicity. Further RCTs are needed to confirm the efficacy superiority of DS-based regimens.

Finger-inspired rigid-soft hybrid tactile sensor with superior sensitivity at high frequency.

Among kinds of flexible tactile sensors, piezoelectric tactile sensor has the advantage of fast response for dynamic force detection. However, it suffers from low sensitivity at high-frequency dynamic stimuli. Here, inspired by finger structure-rigid skeleton embedded in muscle, we report a piezoelectric tactile sensor using a rigid-soft hybrid force-transmission-layer in combination with a soft bottom substrate, which not only greatly enhances the force transmission, but also triggers a significantly magnified effect in d31 working mode of the piezoelectric sensory layer, instead of conventional d33 mode. Experiments show that this sensor exhibits a super-high sensitivity of 346.5 pC N-1 (@ 30 Hz), wide bandwidth of 5-600 Hz and a linear force detection range of 0.009-4.3 N, which is ~17 times the theoretical sensitivity of d33 mode. Furthermore, the sensor is able to detect multiple force directions with high reliability, and shows great potential in robotic dynamic tactile sensing.

A Strategy for Extracting Full Material Coefficients of AlN Thin Film Based on Resonance Method.

AlN thin film is widely used in piezoelectric MEMS devices, and the accurate characterizations of its material coefficients are critical for the optimization of the AlN thin film process and the design of AlN thin-film-based devices. However, it is difficult to extract the material coefficients of AlN in the form of thin film. This paper reports a strategy for systematically extracting full elastic coefficients, piezoelectric coefficients and dielectric constants of c-axis-oriented AlN thin film based on the resonance method outlined in IEEE Standard on Piezoelectricity Std 176-1987. In this strategy, four self-suspended resonators with length thickness extension (LTE), thickness extension (TE), radial extension (RE), lateral electric field excited thickness shear (LEF-TS) modes together with a lamb wave resonator (LWR) are specifically adopted, and the material coefficients of AlN thin film are extracted by measuring the impedance spectra of these resonators. In addition, the effects of the pad and electrodes on the resonators were systematically studied, and the corresponding procedures to eliminate their influences on the extraction accuracy of material coefficients were proposed. Finally, a complete extraction process based on the above strategy was established. The simulation results show that the strategy can achieve high accuracy for AlN thin film with different thicknesses and electrode configurations, and it can also be applied to other materials belonging to the 6 mm piezoelectric crystal class such as ZnO, ScAlN, etc.

ROCK2 Polymorphism and Expression Contribute to Increased Susceptibility and Poor Prognosis in Hepatocellular Carcinoma.

AIM: To analyze the association between ROCK2 gene polymorphism/expression and susceptibility/prognosis of hepatocellular carcinoma (HCC). METHODS: Peripheral venous blood from 204 hepatocellular carcinoma patients (HCC group), 242 chronic hepatitis B patients (CHB group), 215 liver cirrhosis patients (LC group) and 201 healthy volunteers (normal group) were collected. ROCK2 gene (including the rs9808232 locus) was amplified by PCR and the products were sequenced. Tumor tissues from patients with HCC and liver tissues from CHB, LC and normal groups were collected, and mRNA and protein expression of ROCK2 gene in liver tissues were tested by RT-qPCR and immunofluorescence, respectively. RESULTS: Compared with the normal group, the mRNA and protein expression levels of ROCK2 in the HCC group increased significantly (P < 0.05), but there are no obvious increases in the CHB and LC groups (P > 0.05). ROCK2 gene rs9808232 polymorphism was associated with an increased susceptibility of HCC, and genotypes AC and CC may be risk factors for HCC (P < 0.001). There was a significant association between the ROCK2 gene rs9808232 polymorphism and the route of metastasis in HCC patients (P < 0.05). According to the Kaplan-Meier analysis, the overall survival of patients with AC and CC genotypes of ROCK2 rs9808232 was much shorter than that of patients with AA genotype (median overall survival, 25.5 months vs 16.0 months; Log rank P = 0.006). The overall survival time of patients with high ROCK2 expression is much shorter than that of patients with low ROCK2 expression (median overall survival time, 15.0 months vs 20.5 months; Log rank P = 0.008). Compared with genotype AA, the ROCK2 protein levels of genotypes AC and CC were distinctly increased in the HCC group, especially genotype CC (P< 0.05). CONCLUSION: ROCK2 gene rs9808232 polymorphism may contribute to its expression in liver tissue, which may increase the susceptibility and poor prognosis of HCC.

MIF promoter polymorphism increases peripheral blood expression levels, contributing to increased susceptibility and poor prognosis in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is one of the most common malignancies in the world. The etiology and pathogenesis of HCC remain unclear. Macrophage migration inhibitory factor (MIF) plays a critical role in the pathogenesis of hepatocellular carcinoma. The association between MIF polymorphisms and its expression level in HCC has rarely been demonstrated. In the present study, the peripheral blood of 202 patients with HCC (HCC group), 242 patients with chronic hepatitis B (CHB group), 215 patients with liver cirrhosis (LC group) and 227 healthy volunteers (normal group) were collected, DNA was extracted and the target fragment of MIF gene was amplified using PCR. The products were then sequenced, and the expression levels of MIF protein were tested using ELISA. The results showed that the MIF rs755622 polymorphism was associated with an increased susceptibility and metastasis of HCC, and that the genotypes GC and CC were associated with poor prognosis of HCC. Compared with the normal, CHB and LC groups, the expression of MIF in the peripheral blood of the HCC group was significantly increased, and the high expression was associated with to poor prognosis. In the HCC group, MIF protein levels for genotypes GC and CC were increased compared with those of genotype GG. The current study indicated that the MIF rs755622 polymorphism is associated with susceptibility and metastasis of HCC, and that the GC and CC genotypes may be indicators of poor prognosis, which may be ascribed to the MIF rs755622 polymorphism leading to elevated MIF protein expression in peripheral blood.

Modeling of a Rope-Driven Piezoelectric Vibration Energy Harvester for Low-Frequency and Wideband Energy Harvesting.

In this work, a mechanical model of a rope-driven piezoelectric vibration energy harvester (PVEH) for low-frequency and wideband energy harvesting was presented. The rope-driven PVEH consisting of one low-frequency driving beam (LFDB) and one high-frequency generating beam (HFGB) connected with a rope was modeled as two mass-spring-damper suspension systems and a massless spring, which can be used to predict the dynamic motion of the LFDB and HFGB. Using this model, the effects of multiple parameters including excitation acceleration, rope margin and rope stiffness in the performance of the PVEH have been investigated systematically by numerical simulation and experiments. The results show a reasonable agreement between the simulation and experimental study, which demonstrates the validity of the proposed model of rope-driven PVEH. It was also found that the performance of the PVEH can be adjusted conveniently by only changing rope margin or stiffness. The dynamic mechanical model of the rope-driven PVEH built in this paper can be used to the further device design or optimization.

Efficacy and safety of pinaverium bromide combined with flupentixol-melitracen for diarrhea-type irritable bowel syndrome: A systematic review and meta-analysis.

BACKGROUND: There are many trials on the combination of Pinaverium bromide (PB) and Flupentixol-melitracen (FM) in the treatment of diarrhea-type irritable bowel syndrome (IBS-D), but the sample sizes are small, and the research conclusions are inconsistent. Thus, a meta-analysis was performed, aiming to evaluate the efficacy and safety of this combination therapy in patients with IBS-D. METHODS: A systematic literature search was conducted in 7 databases covering the period up to July 2018 to identify randomized controlled trials (RCTs) of PB combined with FM versus PB alone for IBS-D. The primary outcome was the total symptom relief rate. The other outcomes were the adverse events rate, HAMA/SAS score, and HAMD/SDS score. The methodological quality of the RCTs was assessed independently using 6 criteria according to the Cochrane Collaboration. All data were analyzed using Review Manager 5.3. RESULTS: Fifteen RCTs with 1487 participants were identified from 2005 to 2018. Compared with PB alone, 15 RCTs showed significant effects of PB plus FM in terms of improved symptom relief in patients with IBS-D (n = 1487, OR = 5.17, 95%CI, 3.79-7.07, P < .00001). Eleven RCTs reported adverse effects in both the PB plus FM and PB groups, there was no statistically significant difference in the adverse events rate between the 2 groups (n = 1207, OR = 2.91, 95%CI, 0.91-9.28, P = 0.07). Two RCTs and 3 RCTs reported HAMA and HAMD scores respectively, and 3 RCTs reported both SAS and SDS scores. After treatment, the above scores in the PB plus FM group were significantly lower than the PB group (all P < .01). However, the trials were deemed to have a medium risk of bias. CONCLUSIONS: The efficacy of PB combined with FM is superior to PB alone in the treatment of IBS-D, and it is safe for clinical use. However, the conclusions still need to be verified by conducting more large-scale and high-quality RCTs.

CXCL12 and CXCR4 polymorphisms and expressions in peripheral blood from patients of hepatocellular carcinoma.

AIM: To determine if CXCL12 (rs1801157) and CXCR4 (rs2228014) polymorphisms are associated with hepatocellular carcinoma (HCC) susceptibility, and detect their expressions in peripheral blood. METHODS: 206 HCC patients, 252 chronic hepatitis B patients, 221 liver cirrhosis patients and 275 healthy volunteers were recruited. Genes CXCL12 and CXCR4 were amplified and genotyped. Their expression in peripheral blood were detected. RESULTS: CXCL12 rs1801157 and CXCR4 rs2228014 polymorphisms were associated with increased susceptibility of HCC, and genotypes GA/AA and CT/TT may be risk factors of HCC (all p < 0.05). Expressions of CXCL12 and CXCR4 in peripheral blood from HCC patients increased significantly (p < 0.05). CONCLUSION: CXCL12 and CXCR4 polymorphisms may be risk factors for HCC, and they may be potential HCC markers.

Curcumin protects against hepatic stellate cells activation and migration by inhibiting the CXCL12/CXCR4 biological axis in liver fibrosis：A study in vitro and in vivo.

The C-X-C motif chemokine 12/C-X-C chemokine receptor type 4 (CXCL12/ CXCR4) biological axis plays an important role in the pathogenesis of liver fibrosis. Curcumin is known to have an anti-fibrosis effect, but the specific mechanism needs to be elucidated. There is currently no evidence illustrating a connection between curcumin and the CXCL12/CXCR4 axis in liver fibrosis. Here, we investigated the contribution of curcumin on CXCL12/ CXCR4 biological axis in liver fibrosis. Our results showed that curcumin remarkably improved hepatic function and liver fibrosis, and the effects are similar as silymarin. The alleviation of liver fibrosis with curcumin treatment was associated with a reduction of CXCL12, CXCR4, α-SMA and RhoA. In addition, curcumin markedly inhibited the proliferation and migration of HSC-T6 cells. This study indicates that curcumin could protect against hepatic stellate cells activation and migration by inhibiting the CXCL12/CXCR4 biological axis in liver fibrosis.

[Correlation of serum calprotectin level with the range of coronary lesion in patients with acute coronary syndrome].

OBJECTIVE: To examine the serum levels of S100 calcium-binding protein A8/A9 complex (S100A8/ A9) in patients with acute coronary syndrome (ACS) and to explore the relation between the serum levels of S100A8/A9 and the degree of coronary lesion. METHODS: A total of 126 patients with coronary heart disease were enrolled from Xiangya Hospital of Central South University between September 2010 and January 2011, which included 51 patients with unstable angina pectoris (UAP group, n=51), 50 patients with acute myocardial infarction (AMI group, n=50), and 25 patients with stable angina pectoris (SAP group, n=25). Twenty-five healthy volunteers were served as a normal control group (NC group, n=25). According to the coronary artery lesion area, ACS patients were also divided into a single-branch group, a double-branch group and a triple-branch group. Serum levels of S100A8/A9 were measured by enzyme-linked immunosorbent assay on the day when the patients admitted to the hospital and on the day after one-week treatment (UAP group + AMI group). The serum levels were compared among the various branch groups. The short-term prognosis in patients with ACS was investigated by phone follow-up after 3 months. RESULTS: 1) The S100A8/A9 level in the SAP group was significantly higher than that in the normal control group (P<0.05). The serum levels of S100A8/A9 in the UAP group and the AMI group were significantly higher than that in the SAP group (all P<0.05); There was no significant difference in the S100A8/A9 level between the UAP group and the AMI group (P>0.05); 2) After one-week standard treatment, the serum levels of S100A8/A9 in patients with ACS were significantly reduced compared with that at the admission (P<0.01), but it was still elevated compared with that in the normal control group (P<0.01); 3) The serum level of S100A8/A9 in the triple-branch group was significantly higher than that in the single-branch group and the double-branch group (both P<0.05); 4) The short-term prognosis in patients with ACS was not correlated with the serum level of S100A8/A9 (r=0.012, P> 0.05). CONCLUSION: The serum level of S100A8/A9 is significantly elevated in patients with ACS, which might be positively correlated with the number of the coronary lesion branches.