Acupressure: a possible therapeutic strategy for anxiety related to COVID-19: a meta-analysis of randomized controlled trials.

Background: From the end of 2019 to December 2023, the world grappled with the COVID-19 pandemic. The scope and ultimate repercussions of the pandemic on global health and well-being remained uncertain, ushering in a wave of fear, anxiety, and worry. This resulted in many individuals succumbing to fear and despair. Acupoint massage emerged as a safe and effective alternative therapy for anxiety relief. However, its efficacy was yet to be extensively backed by evidence-based medicine. This study aimed to enhance the clinical effectiveness of acupoint massage and extend its benefits to a wider population. It undertakes a systematic review of the existing randomized controlled trials (RCTs) assessing the impact of acupoint massage on anxiety treatment, discussing its potential benefits and implications. This research aims to furnish robust evidence supporting anxiety treatment strategies for patients afflicted with COVID-19 disease and spark new approaches to anxiety management. Objectives: This study evaluates the evidence derived from randomised controlled trials (RCTs), quantifies the impact of acupressure on anxiety manifestations within the general population, and proposes viable supplementary intervention strategies for managing COVID-19 related anxiety. Materials and methods: This review included RCTs published between February 2014 and July 2023, that compared the effects of acupressure with sham control in alleviating anxiety symptomatology as the outcome measure. The studies were sourced from the multiple databases, including CINAHL, EBM Reviews, Embase, Medline, PsycINFO, Scopus and Web of Science. A meta-analysis was performed on the eligible studies, and an overall effect size was computed specifically for the anxiety outcome. The Cochrane Collaboration Bias Risk Assessment Tool (RevMan V5.4) was employed to assess bias risk, data integration, meta-analysis, and subgroup analysis. The mean difference, standard mean deviation, and binary data were used to represent continuous outcomes. Results: Of 1,110 studies of potential relevance, 39 met the criteria for inclusion in the meta-analysis. The majority of the studies reported a positive effect of acupressure in assuaging anticipatory anxiety about treatment. Eighteen studies were evaluated using the STAI scale. The acupressure procedures were thoroughly documented, and studies exhibited a low risk of bias. The cumulative results of the 18 trials showcased a more substantial reduction in anxiety in the acupressure group compared to controls (SMD = -5.39, 95% CI -5.61 to -5.17, p < 0.01). A subsequent subgroup analysis, based on different interventions in the control group, demonstrated improvement in anxiety levels with sham acupressure in improving changes in anxiety levels (SMD -1.61, 95% CI: -2.34 to -0.87, p < 0.0001), and blank controls (SMD -0.92, 95% CI: -2.37 to 0.53, p = 0.22). Conclusion: In the clinical research of traditional Chinese medicine treatment of anxiety, acupressure demonstrated effectiveness in providing instant relief from anxiety related to multiple diseases with a medium effect size. Considering the increasing incidence of anxiety caused by long COVID, the widespread application of acupressure appears feasible. However, the results were inconsistent regarding improvements on physiological indicators, calling for more stringent reporting procedures, including allocation concealment, to solidify the findings.

Prevalence and factors associated with fertility desires among HIV-positive MSM.

The National surveillance data showed that homosexual transmission played a considerable role in new HIV infections in China. The emphasis on antiretroviral therapy and prevention of mother-to-child transmission provided chances for reproduction among people living with HIV/AIDS. Issues of fertility desire have a paucity of data among HIV-positive men who have sex with men (MSM). This cross-sectional study has assessed fertility attitudes and associated factors, as well as the reproductive knowledge among HIV-positive MSM. Analysis was mainly based on the multinomial regression model. The study included 129 participants, and almost all of the participants (96.1%) were between 18 and 30 years old and 82.2% of them were single. About 35.6% expressed a fertility desire. MSM without siblings tended to have fertility desire (OR = 0.236, 95%CI: 0.078∼0.712, p = 0.010). Surrogacy (36.4%) was the most desired method among the 86 respondents who had the desire or did not make a decision. While the accuracy of the reproductive knowledge was only 69.6%. In summary, we recommend that providers offer much more professional information and develop assisted reproductive technology to meet the reproductive aspirations of HIV-positive MSM.

Probing the Effect of Photovoltaic Material on Voc in Ternary Polymer Solar Cells with Non-Fullerene Acceptors by Machine Learning.

The power conversion efficiency (PCE) of ternary polymer solar cells (PSCs) with non-fullerene has a phenomenal increase in recent years. However, improving the open circuit voltage (Voc) of ternary PSCs with non-fullerene still remains a challenge. Therefore, in this work, machine learning (ML) algorithms are employed, including eXtreme gradient boosting, K-nearest neighbor and random forest, to quantitatively analyze the impact mechanism of Voc in ternary PSCs with the double acceptors from the two aspects of photovoltaic materials. In one aspect of photovoltaic materials, the doping concentration has the greatest impact on Voc in ternary PSCs. Furthermore, the addition of the third component affects the energy offset between the donor and acceptor for increasing Voc in ternary PSCs. More importantly, to obtain the maximum Voc in ternary PSCs with the double acceptors, the HOMO and LUMO energy levels of the third component should be around (-5.7 ± 0.1) eV and (-3.6 ± 0.1) eV, respectively. In the other aspect of molecular descriptors and molecular fingerprints in the third component of ternary PSCs with the double acceptors, the hydrogen bond strength and aromatic ring structure of the third component have high impact on the Voc of ternary PSCs. In partial dependence plot, it is clear that when the number of methyl groups is four and the number of carbonyl groups is two in the third component of acceptor, the Voc of ternary PSCs with the double acceptors can be maximized. All of these findings provide valuable insights into the development of materials with high Voc in ternary PSCs for saving time and cost.

Design, Manufacture, and Experimental Validation of a Hydraulic Semi-Active Knee Prosthesis.

In this article, a new hydraulic semi-active knee (HSAK) prosthesis is proposed. Compared with knee prostheses driven by hydraulic-mechanical coupling or electromechanical systems, we novelly combine independent active and passive hydraulic subsystems to solve the incompatibility between low passive friction and high transmission ratio of current semi-active knees. The HSAK not only has the low friction to follow the intentions of users, but also performs adequate torque output. Moreover, the rotary damping valve is meticulously designed to effectively control motion damping. The experimental results demonstrate the HSAK combines the advantages of both passive and active prostheses, including the flexibility of passive prostheses, as well as the stability and the sufficient active torque of active prostheses. The maximum flexion angle in level walking is about 60°, and the peak output torque in stair ascent is greater than 60Nm. Relative to the daily use of prosthetics, the HSAK improves gait symmetry on the affected side and contributes to the amputees better maintain daily activities.

Heat treatment-induced autophagy promotes breast cancer cell invasion and metastasis via TGF-ß2-mediated epithelial-mesenchymal transitions.

Background: Insufficient thermal ablation can accelerate malignant behaviors and metastases in some solid tumors, and epithelial-mesenchymal transition (EMT) and autophagy are involved in tumor metastasis. It has been found that TGF-ß2 which belongs to the family of transforming growth factors often associated with cancer cell invasiveness and EMT. However, whether the interactions between autophagy and TGF-ß2 induce EMT in breast cancer (BC) cells following insufficient microwave ablation (MWA) remains unclear. Methods: BC cells were treated with sublethal heat treatment to simulate insufficient MWA, and the effects of heat treatment on the BC cell phenotypes were explored. CCK-8, colony formation, flow cytometry, Transwell, and wound healing assays were performed to evaluate the influence of sublethal heat treatment on the proliferation, apoptosis, invasion, and migration of BC cells. Western blotting, real-time quantitative PCR, immunofluorescence, and transmission electron microscopy were carried out to determine the changes in markers associated with autophagy and EMT following sublethal heat treatment. Results: Results showed that heat treatment promoted the proliferation of surviving BC cells, which was accompanied by autophagy induction. Heat treatment-induced autophagy up-regulated TGF-ß2/Smad2 signaling and promoted EMT phenotype, thereby enhancing BC cells' migration and invasion abilities. An increase or decrease of TGF-ß2 expression resulted in the potentiation and suppression of autophagy, as well as the enhancement and abatement of EMT. Autophagy inhibitors facilitated apoptosis and repressed proliferation of BC cells in vitro, and thwarted BC cell tumor growth and pulmonary metastasis in vivo. Conclusion: Heat treatment-induced autophagy promoted invasion and metastasis via TGF-ß2/Smad2-mediated EMTs. Suppressing autophagy may be a suitable strategy for overcoming the progression and metastasis of residual BC cells following insufficient MWA.

Design, fabrication and experiments of a hydraulic active-passive hybrid prosthesis knee.

BACKGROUND: Due to low friction, passive mechanical prostheses move compliantly followed by the stump and are used widely. Advanced semi-active prostheses can both move passively like passive prostheses and provide active torque under specific conditions. However, the current mechanical-hydraulic coupling driven semi-active prostheses, in order to meet the low passive friction requirements with a low active transmission ratio, lead to a significant problem of insufficient active torque. OBJECTIVE: A hybrid active and passive prosthesis was developed to solve the incompatibility problem of low passive friction and high active driving torque of semi-active prostheses. METHODS: The mechanical structure and control strategy of the prosthesis were demonstrated. The performance of the prosthesis was tested by bench and human tests. RESULTS: Passive subsystem damping adjustment ranges from 0.4 N⋅(mm/s)-1 to 300 N⋅(mm/s)-1. The switching time between the damping and the active subsystem is 32 ± 2 ms. The continuous active torque output is more than 24 Nm. In level walking, the peak torque is about 28 Nm. CONCLUSION: The proposed active-passive hybrid hydraulic prosthesis could satisfy both low passive friction and high active actuation.

An extensive bioinformatics study on the role of mitochondrial solute carrier family 25 in PC and its mechanism behind affecting immune infiltration and tumor energy metabolism.

BACKGROUND: Several metabolic disorders and malignancies are directly related to abnormal mitochondrial solute carrier family 25 (SLC25A) members activity. However, its biological role in pancreatic cancer (PC) is not entirely understood. METHODS: The lasso method was used to create a novel prognostic risk model for PC based on SLC25A members, and its roles in tumor immunology and energy metabolism were explored. Furthermore, co-expression networks were constructed for SLC25A11, SLC25A29, and SLC25A44. Single-cell RNA sequencing (ScRNA-seq) revealed the distribution of gene expression in PC. Tumor immune infiltration was examined with the TIMER database. Lastly, drug sensitivity was investigated, and co-transcriptional factors were predicted. RESULTS: In the present study, a novel prognostic risk model was established and validated for PC based on SLC25A members. The high-risk group had a lower activation of oxidative phosphorylation and a more abundant immune infiltration phenotype than the low-risk group. According to co-expression network studies, SLC25A11, SLC25A29, and SLC25A44 were involved in the energy metabolism of PC and prevented tumor growth, invasion, and metastasis. ScRNA-seq research also pointed to their contribution to the tumor microenvironment. Moreover, the recruitment of numerous immune cells was positively correlated with SLC25A11 and SLC25A44 but negatively correlated with SLC25A29. Additionally, the sensitivity to 20 Food and Drug Administration-approved antineoplastic medicines was strongly linked to the aforementioned genes, where cisplatin sensitivity increased with the up-regulation of SLC25A29. Finally, the Scleraxis BHLH Transcription Factor (SCX) and other proteins were hypothesized to co-regulate the mRNA transcription of the genes. CONCLUSION: SLC25A members are crucial for tumor immune and energy metabolism in PC, and SLC25A11, SLC25A29, and SLC25A44 can be used as favorable prognostic markers. The use of these markers will provide new directions to unravel their action mechanisms in PC.

Dysregulated hepatic UDP-glucuronosyltransferases and flavonoids glucuronidation in experimental colitis.

Glucuronidation catalyzed by UDP-glucuronosyltransferases (UGTs) is one of the most important phase II mechanisms, facilitating drug clearance via conjugation of glucuronic acid with polar groups of xenobiotics. Accumulating evidence suggests that IBDs impact drug disposition, but whether and how IBDs regulate UGTs and drug glucuronidation remains undefined. In this study, we aim to investigate the expression of UGTs and drug glucuronidation in experimental colitis. Given that glucuronidation occurs primarily in the liver, we analyzed the mRNA changes in hepatic UGTs with a DSS-induced mouse colitis model. Twelve UGTs were downregulated in the liver of colitis mice including UGT1A1 and UGT1A9 (two representative UGTs). Colitis in mice downregulated UGT1A1 and UGT1A9 in the liver but not in small intestine, colon, and kidney. We also established that the downregulation of UGTs was attributed to the disease itself rather than the DSS compound. Moreover, colitis-reduced UGT1A1 and UGT1A9 lead to dampened baicalein and puerarin glucuronidation. PXR was the only UGT regulator significantly downregulated in colitis mice, suggesting dysregulation of PXR is associated with the downregulation of UGT1A1 and UGT1A9, thereby potentially resulting in dysfunction of baicalein and puerarin glucuronidation. Collectively, we establish that UGTs and glucuronidation are dysregulated in colitis, and this effect may cause variation in drug responsiveness in IBDs.

Accelerated exploration of efficient ternary solar cells with PTB7:PC71BM:SMPV1 using machine-learning methods.

Machine learning (ML) provides an efficient tool for predicting the photoelectric conversion efficiency (PCE) of organic solar cells (OSCs). In this paper, random forest (RF), K-nearest neighbors, and support vector machine are used to predict the PCE for ternary OSCs with PC71BM. The results of ML show that RF has the best PCE prediction accuracy. Therefore, RF is chosen to predict the champion PCE of ternary OSCs with PTB7:PC71BM:SMPV1, which is around 8.01% in ternary OSCs with a doping ratio of around 6 wt% of SMPV1. To check the prediction, ternary OSCs with PTB7:PC71BM:SMPV1 were fabricated, and the experimental results show that the best PCE of 8.83% is obtained in ternary OSCs with 7.5 wt% of SMPV1 introduced. The experiments verify the feasibility of ML in predicting the PCE of ternary OSCs, and its great potential in predicting the doping concentration of the third component for ternary OSCs. Moreover, the working mechanism of the performance enhancement in the ternary OSCs is further researched and demonstrated as the following: (i) an increase in photon capture in the visible light spectrum to enhance the short circuit current density (Jsc); (ii) high priority charge transport to boost the fill factor and Jsc.

Factors Associated with Shoulder Range of Motion After Arthroscopic Rotator Cuff Repair: A Hospital-Based Prospective Study.

OBJECTIVE: To assess the factors associated with outcomes of arthroscopic surgical repair of rotator cuff tears (RCTs). METHOD: This prospective study recruited patients, at least 18 years old, who underwent arthroscopic rotator cuff repair for full-thickness RCTs at the First People's Hospital of Hangzhou Xiaoshan between July 2019 and October 2020. Patient demographics, lifestyle habits, and medical histories were collected preoperatively; RCT sizes and affected tendons were determined intraoperatively. Outcomes were assessed by shoulder range of motion (ROM) determinations 1.5 and 3 months postoperatively. The factors associated with ROM were determined using a binary logistic regression analysis, and the results were expressed as adjusted relative risks (RRs) and 95% confidence intervals (CIs). RESULTS: A total of 132 patients with RCTs underwent arthroscopic surgery. Five were lost to follow-up, leaving 127 patients (mean age, 59 years; 58.3% women) who were included in the study analysis. The majority of the patients (54.5%) had RCTs that were classified as large or massive, and approximately 20% had tears involving multiple tendons; 80.3% of the patients had tears involving only a single tendon. Moreover, 29.9% of the patients had hypertension and 11.0% had diabetes. Among the patients, 23.0% were smokers and 34.6% drank alcohol. According to the multivariate analysis, none of the assessed factors were associated with shoulder ROM at the 1.5-month follow-up. At the 3-month follow-up, RCTs involving a single tendon demonstrated 3-fold better abduction (RR = 4.00; 95% CI, 1.30-12.33; P = 0.016) and 3.15-fold better internal rotation (RR = 3.15; 95% CI, 1.19-8.36; P = 0.021) than did RCTs involving multiple tendons. Patients who did not drink alcohol demonstrated 6.08-fold better anteflexion (RR = 7.08; 95% CI, 2.11-23.73; P = 0.002) and nearly 4-fold better abduction (RR = 4.97; 95% CI, 1.62-15.23; P = 0.005) than patients who drank alcohol. CONCLUSION: To improve outcomes, the results indicate that more targeted measures should be directed toward patients with multiple-tendon RCTs and that preoperative alcohol abstinence education is needed for patients with RCTs.

FAM81A identified as a stemness-related gene by screening DNA methylation sites based on machine learning-accessed stemness in pancreatic cancer.

Aim: We thoroughly discuss the interaction between the stemness index and DNA methylation in pancreatic cancer (PC). Materials & methods: First, the stemness indices of PC (denoted mRNAsi and mDNAsi) were calculated using a one-class logistic regression machine-learning algorithm. Second, we screened the central methylation sites associated with stemness and screened out the key genes. We investigated the DNA methylation regulators associated with the key genes. Finally, using CIBERSORT and TIMER, we assessed the influence of stemness indexes and key genes on PC microenvironment formation. Results: In this study we quantified the stemness indices for PC and screened 20 related central DNA methylation sites. Further analysis of the methylation site cg22687244, located in the 3' UTR, revealed that it promoted the expression of the key gene FAM81A. We show that FAM81A may be regulated by DNA methylation regulators. Furthermore, immune cells were found to be more abundant in PC microenvironments with high expression of FAM81A. Conclusion: We report for the first time that the 3' UTR methylation of FAM81A is closely related to PC stemness and contributes to tumor immune infiltration. Therefore FAM81A may serve as a potential marker to guide the treatment of PC.

Design of Building Environment Detection System for Architectures Based on Internet of Things.

In the process of urban building design, a new integrated system for monitoring the environment is developed and designed by using embedded development technology and sensor technology. The system uses a wireless sensor network environment monitoring system IoT platform with embedded internal processors. Analyze and design the system as a whole, including the construction of the basic platform of the system, the design of the internal plates and circuits of the system, the monitoring design of the input node, and the monthly design of the output interface calculation. Finally, a physical model is built, and data measurement and analysis are carried out under different conditions, and the evaluation and advantage analysis of the system's operating status are given. The system can carry out all-round, multilevel, and three-dimensional real-time monitoring of the construction site environment, including dust, PM2.5, temperature, humidity, wind speed, carbon dioxide, and other indicators in the construction site environment. In addition, the system can upload various monitoring data to the detection system through the internal network. The system has the functions of monitoring, alarming, recording, querying, and counting of the target monitoring station and can also be linked with the environmental control device. The construction site staff can conduct real-time supervision through the mobile terminal and computer terminal management platform. In addition, it can also meet the role of real-time remote monitoring and online guidance and regulation. It has reference value for the safety and management of the actual operation process of the project.

A fluid-driven soft robotic fish inspired by fish muscle architecture.

Artificial fish-like robots developed to date often focus on the external morphology of fish and have rarely addressed the contribution of the structure and morphology of biological muscle. However, biological studies have proven that fish utilize the contraction of muscle fibers to drive the protective flexible connective tissue to swim. This paper introduces a pneumatic silicone structure prototype inspired by the red muscle system of fish and applies it to the fish-like robot named Flexi-Tuna. The key innovation is to make the fluid-driven units simulate the red muscle fiber bundles of fish and embed them into a flexible tuna-like matrix. The driving units act as muscle fibers to generate active contraction force, and the flexible matrix as connective tissue to generate passive deformation. Applying alternant pressure to the driving units can produce a bending moment, causing the tail to swing. As a result, the structural design of Flexi-Tuna has excellent bearing capacity compared with the traditional cavity-type and keeps the body smooth. On this basis, a general method is proposed for modeling the fish-like robot based on the independent analysis of the active and passive body, providing a foundation for Flexi-Tuna's size design. Followed by the robot's static and underwater dynamic tests, we used finite element static analysis and fluid numerical simulation to compare the results. The experimental results showed that the maximum swing angle of the tuna-like robot reached 20°, and the maximum thrust reached 0.185 N at the optimum frequency of 3.5 Hz. In this study, we designed a unique system that matches the functional level of biological muscles. As a result, we realized the application of fluid-driven artificial muscle to bionic fish and expanded new ideas for the structural design of flexible bionic fish.

Comparison of surface properties, cell behaviors, bone regeneration and osseointegration between nano tantalum/PEEK composite and nano silicon nitride/PEEK composite.

Both tantalum (Ta) and silicon nitride (SN) exhibit osteogenic bioactivity and antibacterial property. In addition, as a biomaterial for bone repair, polyetheretherketone (PEEK) has outstanding biocompatibility and mechanical performances while it is biologically inert. In this study, by blending PEEK with Ta and SN nanoparticles, respectively, Ta/PEEK composite (TPC) and SN/PEEK composite (SPC) were fabricated for load-bearing bone repair. The surface roughness, hydrophilicity and surface energy of TPC containing Ta nanoparticles were higher than SPC containing SN nanoparticles and PEEK. In addition, TPC with Ta nanoparticles exhibited low antibacterial property while SPC with SN nanoparticles showed high bacterial property. Moreover, the MC3T3-E1 cells responses (e.g. proliferation and differentiation) to TPC was the highest while PEEK was the lowest in vitro. Furthermore, new bone formation and osseointegration for TPC was the highest while PEEK was the lowest in vivo. In conclusion, compared with PEEK, addition of Ta and SN nanoparticles into PEEK fabricated bioactive composites of TPC and SPC with optimized surface property, which played crucial roles in inducing cellular response/bone regeneration. Although the osteogenic activity of SPC was lower than TPC, SPC exhibited osteogenic activity and good antibacterial property, which could prevent infection from bacterial. Therefore, SPC would have better potential for bone substitute.

Clinical Observation on the Treatment of Rotator Cuff Injury with Modified Buyang Huanwu Decoction and Rotator Cuff Repair.

In this paper, we have evaluated the clinical efficacy of rotator cuff surgery combined with Chinese medicine Buyang Huanwu Decoction (adding medicine) in the treatment of patients with rotator cuff injury. For this purpose, sixty patients with rotator cuff injury and shoulder arthroscopic surgery were selected in this hospital (where 57 cases were finally screened). The patients were divided into a control group (28 cases) and a study group (29 cases) by the envelope method. The control group received conventional treatment after the operation, whereas the study group was combined with Buyang Huanwu Decoction after the operation. The clinical efficacy of the two groups, particularly after treatment, was compared in terms of self-care ability and Constant-Murley scores before and after treatment, that is, 4 w, 8 w, and 12 w. The total effective rate of treatment in the study group was significantly higher than that of the control group after 4 weeks of treatment (P < 0.05). There was no significant difference in the FIM self-care scores of the two groups before treatment (P > 0.05). In the study group patients, after treatment for 4 w and 8 w, the FIM self-care score was significantly improved (P < 0.05). The FIM self-care score of the patients in the study group, after 12 w of treatment, had no significant difference compared with the control group (P > 0.05). The Constant-Murley scores of the two groups were compared before treatment where no significant difference is observed (P > 0.05) and the Constant-Murley score of the study group patients was significantly higher than that of the control group, after 4 w and 8 w treatment (P < 0.05). Additionally, Constant-Murley score of the study group was not significantly higher than that of the control group after 12 w of treatment difference (P > 0.05). The proposed combined treatment program has value of promotion and implementation in the clinical treatment of patients with rotator cuff injury.

Establishment of a Prognostic Model for Hepatocellular Carcinoma Based on Endoplasmic Reticulum Stress-Related Gene Analysis.

Hepatocellular carcinoma (HCC) is one of the most common types of cancer worldwide and its incidence continues to increase year by year. Endoplasmic reticulum stress (ERS) caused by protein misfolding within the secretory pathway in cells and has an extensive and deep impact on cancer cell progression and survival. Growing evidence suggests that the genes related to ERS are closely associated with the occurrence and progression of HCC. This study aimed to identify an ERS-related signature for the prospective evaluation of prognosis in HCC patients. RNA sequencing data and clinical data of patients from HCC patients were obtained from The Cancer Genome Atlas (TCGA) and The International Cancer Genome Consortium (ICGC). Using data from TCGA as a training cohort (n=424) and data from ICGC as an independent external testing cohort (n=243), ERS-related genes were extracted to identify three common pathways IRE1, PEKR, and ATF6 using the GSEA database. Through univariate and multivariate Cox regression analysis, 5 gene signals in the training cohort were found to be related to ERS and closely correlated with the prognosis in patients of HCC. A novel 5-gene signature (including HDGF, EIF2S1, SRPRB, PPP2R5B and DDX11) was created and had power as a prognostic biomarker. The prognosis of patients with high-risk HCC was worse than that of patients with low-risk HCC. Multivariate Cox regression analysis confirmed that the signature was an independent prognostic biomarker for HCC. The results were further validated in an independent external testing cohort (ICGC). Also, GSEA indicated a series of significantly enriched oncological signatures and different metabolic processes that may enable a better understanding of the potential molecular mechanism mediating the progression of HCC. The 5-gene biomarker has a high potential for clinical applications in the risk stratification and overall survival prediction of HCC patients. In addition, the abnormal expression of these genes may be affected by copy number variation, methylation variation, and post-transcriptional regulation. Together, this study indicated that the genes may have potential as prognostic biomarkers in HCC and may provide new evidence supporting targeted therapies in HCC.

Expression and prognostic analyses of SCAMPs in pancreatic adenocarcinoma.

Due to the difficulties in early diagnosis of pancreatic adenocarcinoma (PAAD), many patients fail to receive optimal therapeutic regimens. The Secretory-Carrier-Membrane-Proteins (SCAMPs) are known to be dysregulated in a range of human diseases due to their characterized roles in mammalian cell exocytosis inferred from their functions as integral membrane proteins. However, the expression and prognostic value of SCAMPs in PAAD is poorly characterized. We compared cancer vs. healthy tissue and found that the expression of SCAMPs1-4 was upregulated in PAAD compared to normal tissue. In contrast, SCAMP5 expression was downregulated in PAAD. Moreover, the expression of SCAMPs1-4 was enhanced in PAAD cell lines according to Cancer Cell Line public database. Furthermore, the HPA, GEPIA databases and immunohistochemical analysis from 238 patients suggested that the loss of SCAMP1 led to improved overall survival (OS), whilst lower SCAMP5 levels led to a poorer OS. The univariate and multivariate analysis showed that SCAMP1 and SCAMP5 expression were independent prognostic factors of PAAD. In addition, the cBioPortal for Cancer Genomics, LinkedOmics datasets, and the GEPIA were used to identify the co-expression genes of SCAMP1,5 and the correlation between SCAMPs members. We conclude that SCAMPs 1 and 5 significantly represent promising diagnosis and prognostic biomarkers.

Oral Administration of Nanoiron Sulfide Supernatant for the Treatment of Gallbladder Stones with Chronic Cholecystitis.

Cholelithiasis with chronic cholecystitis is prevalent and threatens human health. Most cholecystitis caused by bacterial infection or biofilms is accompanied by gallstones in the clinic, making gallbladder removal the only effective solution. Here, we provide a strategy to eliminate gallstone biofilms and dissolve gallstones by oral administration of a supernatant derived from nanoscale iron sulfide (nFeS supernatant). First, by using gallstones obtained from the clinic, we simulated biofilm formation on gallstones and tested the antibacterial activity of a nFeS supernatant in vitro. We found that the supernatant kills bacteria with a 5-log reduction in viability and destroys the biofilm structure. Smashed gallstones coincubated with E. coli biofilms promote gallstone formation, while nFeS supernatant can inhibit this process. Second, by using a murine (C57BL/6) model of cholelithiasis and cholecystitis, we tested the antibacterial efficacy and therapeutic effects of nFeS supernatant on cholelithiasis in vivo. Animal experimental data show that oral administration of nFeS supernatant can reduce 60% of bacteria in the gallbladder and, remarkably, remove gallstones with 2 days of treatment compared with clinical drug combinations (chenodeoxycholid acid and ciprofloxacin). Third, by performing protein abundance analysis of L02 cells and mouse livers, we observed the changes in CYP7a1, HMGCR, and SCP2 expression, indicating that the nFeS supernatant can also regulate cholesterol metabolism to prevent gallstone formation. Finally, hematologic biochemistry analysis and high-throughput sequencing technology show that the nFeS supernatant possesses high biocompatibility. Therefore, our work demonstrates that the nFeS supernatant may be a potential regimen for the treatment of cholelithiasis and cholecystitis by oral administration.

High Expression of COL17A1 Predicts Poor Prognosis and Promotes the Tumor Progression via NF-κB Pathway in Pancreatic Adenocarcinoma.

COL17A1 (collagen type XVII alpha 1 chain) is known to be upregulated and has a prognostic role in many malignancies, as well as contributing to cell proliferation, apoptosis, and invasion. However, little knowledge is available on the expression and prognostic value of COL17A1 in pancreatic adenocarcinoma (PDAC). In our study, we searched the public database and found that mRNA and protein levels of COL17A1 are commonly upregulated in PDAC tissues. The immunohistochemical analysis conducted by us revealed enhanced expression of COL17A1 protein in 169 PDAC samples compared with that in 67 adjacent normal tissues. We also observed a significantly positive correlation between COL17A1 expression and lymph node metastasis (p < 0.0001), TNM clinical stage (p < 0.0001), and pathology differentiation (p < 0.01). The KM-plot results indicated that PDAC patients with a high COL17A1 expression have a poorer overall survival (p < 0.001) than those with a low COL17A1 expression. The result of the Cox regression analysis of multivariate data suggested COL17A1 is an independent prognostic indicator of PDAC patients' overall survival. CCK-8, wound healing, and transwell assays suggested that COL17A1 knockdown markedly inhibited tumor proliferation and invasion in PDAC cells, and cells with COL17A1 overexpression had a prominently higher proliferative and invasive capacity. Knockdown of COL17A1 significantly upregulated the apoptosis rate. We deduce that upregulated COL17A1 activated the NF-κB pathway in PDAC cells. In summary, our studies showed the prognostic value of COL17A1 in PDAC and that COL17A1 may act as a molecular therapeutic target for PDAC treatment.

Primary prophylaxis for venous thromboembolism in ambulatory cancer patients: a systematic review and network meta-analysis.

BACKGROUND: Ambulatory cancer patients carry a high risk of venous thromboembolism (VTE). However, the optimal prophylaxis strategy remains controversial. This meta-analysis compared the effectiveness and safety of apixaban, rivaroxaban, low molecular weight heparin (LMWH), semuloparin, aspirin, and warfarin for the prevention of VTE in ambulatory cancer patients. METHODS: A systematic review and network meta-analysis was performed. PubMed, the Cochrane Central Register of Controlled Trails (CENTRAL) and EMBASE electronic databases were searched from inception to 26 April 2019. In the meta-analysis, 19 randomized controlled trials (RCTs) in ambulatory cancer patients administrated venous thromboprophylaxis agents were included. The primary outcome was the risk of VTE. Safety outcomes included the occurrence of major-bleeding. Two investigators identified the studies and performed data extraction. A network meta-analysis was performed and agents were ranked using cumulative ranking (SUCRA) probabilities. RESULTS: We identified 19 studies, including 11,430 patients comparing 10 interventions. Compared to placebo controls, apixaban (5 mg) showed the highest efficacy for the prevention of VTE [odds ratio (OR) 0.36, 95% confidence interval (CI): 0.18-0.71, SUCRA=69.5] and was more effective than LMWH (OR 0.5, 0.39-0.63; SUCRA=52.1) or warfarin (OR 0.75, 95% CI: 0.35-1.59; SUCRA=25.6). Moreover, the safety of apixaban (5 mg) (OR 1.41, 95% CI: 0.33-5.93; SUCRA=58.5) was higher than LMWH (OR 1.96, 95% CI: 0.99-3.86; SUCRA=44.1) or warfarin (OR 3.06, 95% CI: 1.03-9.08; SUCRA=29.1). There were no significant differences between placebo and experimental groups in terms of patient deaths. CONCLUSIONS: Anticoagulation therapies in ambulatory cancer patients can significantly reduce the risk of VTE. However, this protective effect was associated with a significantly increased risk of major bleeding. Apixaban at the appropriate dose can decrease the risk of VTE without increasing the bleeding risk. These findings require validation in larger study cohorts.