Three-dimensional (3D) printing has provided individuals in various industries with a tool to bring their creations to life. The medical field is no stranger to 3D printing, which has been utilized in various applications since its inception. The various additive technologies currently available to elucidate the differences between them will be discussed briefly. The current applications of 3D printing in medicine could be divided into applications in medical education, patient care, equipment modification or fabrication, and research. The various applications in these categories are described with examples of upcoming research and technology that may be available in the near future. Despite the benefits of 3D printing, challenges remain, and technology improvements are required before there will be more adoption in the medical field. The technology is growing rapidly and evolving, and more 3D printing applications will be seen in the future.

Lasting LPS stimulation changes macrophages toward the M2 phenotype therefore resulting in immunodepression. Melatonin can improve sleep, adjust the time difference, regulate immunity, and anti-tumor. This study is to observe whether melatonin can induce M2 macrophage apoptosis to reverse lasting LPS-induced immunodepression for lung cancer prevention and explore the possible mechanism.

The effects of LPS alone or in combination with melatonin on macrophage phenotypes were assessed by surface markers, morphological changes, cytokines, autophagy, and autophagic efflux. The anti-cancer effect was evaluated in the lung carcinogenic model and lung cancer allograft model. Melatonin-related targets and pathways were predicted by network pharmacology.

Single LPS stimulation polarized macrophages to M1 phenotype, whereas LPS stimulation lasting for 7d polarized macrophages to M2 phenotype. However, combination treatment of lasting LPS and 10 µM melatonin inhibited the polarization of macrophages towards an M2-like phenotype and exerted a continuous antitumor effect. In the urethane-induced lung carcinoma model, long-lasting LPS administration (>4 times) facilitated macrophage polarization toward the M2 phenotype and promoted lung carcinogenesis, which was abrogated by macrophage depletion, while melatonin alone or in combination with lasting LPS could decrease M2-like macrophages and prevented carcinogenesis. In the Lewis lung cancer allograft model, melatonin decreased M2 macrophages and promoted the tumor-suppressing effect of short-term LPS administration (<4 times). Network pharmacology indicated that melatonin regulates macrophages by targeting the multi-protein network.

Melatonin as a key maintainer of macrophage phenotype can induce LPS-stimulated M2 macrophage apoptosis to reverse system immunodepression for lung cancer prevention.

Emerging evidence has demonstrated that abnormal body composition may potentiate the development of frailty, whereas little work focuses on the role of divergent adipose tissue. Therefore, we aimed to determine the potential contribution of adipose tissue distribution to multidimensional frailty in decompensated cirrhosis.

We conducted a retrospective cohort study. Divergent adipose tissues were assessed by computed tomography-derived subcutaneous adipose tissue index (SATI), visceral adipose tissue index (VATI) and total adipose tissue index (TATI), respectively. Frailty was identified by our validated self-reported Frailty Index. Multiple binary logistic models incorporating different covariates were established to assess the relationship between adipose tissue distribution and frailty.

The study cohort comprised 245 cirrhotic patients with 45.3% being male. The median Frailty Index, body mass index (BMI) and model for end-stage liver disease (MELD) score were 0.11, 24.3 kg/m2 and 8.9 points, respectively. In both men and women, patients who were frail exhibited lower levels of SATI in comparison with nonfrail patients. SATI inversely correlated with Frailty Index in the entire cohort (rs=−0.1361, p=0.0332). Furthermore, SATI or TATI was independently associated with frail phenotype in several multiple logistic regression models adjusting for age, BMI, presence of ascites, sodium, Child-Pugh class or MELD score in isolation.

In the context of decompensated cirrhosis, low SATI and concomitant TATI were associated with higher risk of being frail. These findings highlight the importance to further apply tissue-specific tools of body composition in place of crude metric like BMI.

The goal of this study was to investigate the mechanism by which the long noncoding RNA MALAT1 inhibited hepatocyte proliferation in acute liver injury (ALI).

Lipopolysaccharide (LPS) was used to induce an ALI cellular model in HL7702 cells, in which lentivirus vectors containing MALAT1/EZH2/GFER overexpression or knockdown were introduced. A series of experiments were performed to determine their roles in liver injury, oxidative stress injury, and cell biological processes. The interaction of MALAT1 with EZH2 and enrichment of EZH2 and H3K27me3 in the GFER promoter region were identified. Rats were treated with MALAT1 knockdown or GFER overexpression before LPS induction to verify the results derived from the in vitro assay.

MALAT1 levels were elevated and GFER levels were reduced in ALI patients and the LPS-induced cell model. MALAT1 knockdown or GFER overexpression suppressed cell apoptosis and oxidative stress injury induced cell proliferation, and reduced ALI. Functionally, MALAT1 interacted directly with EZH2 and increased the enrichment of EZH2 and H3K27me3 in the GFER promoter region to reduce GFER expression. Moreover, MALAT1/EZH2/GFER was activated the AMPK/mTOR signaling pathway.

Our study highlighted the inhibitory role of reduced MALAT1 in ALI through the modulation of EZH2-mediated GFER.

Carissa edulis (Apocynaceae) is a wild fruit species highly consumed by Cameroonian populations because of its many biological effects. However, few studies so far have addressed the nutritional, antioxidant, and physicochemical properties of this plant.

Juice and cake powders obtained from C. edulis fruits were examined for their contents in macronutrients, micronutrients, and phenolic compounds through conventional methods. Then, the in vitro antioxidant properties were assessed using the 1,1-diphenyl-2-picrylhydrazyl radical scavenging, total reducing power, and the total antioxidant capacity assays.

The results showed that cakes displayed significantly higher fat (22.68 ± 2.16 vs 5.06 ± 0.43 g/100 g dry weight (DW)), carbohydrates (39.25 ± 1.16 vs 19.29 ± 0.55 g/100 g DW), protein (1.32 ± 0.56 vs 0.23 ± 0.13 g/100 g DW), zinc, copper, and calcium levels compared to juice. However, their ash (0.28 ± 0.02 vs 0.31 ± 0.02 g/100 g DW), moisture (5.67 ± 0.53 vs 14.40 ± 1.36 g/100 g), carotenoids, and Vitamin C levels were significantly lower. The phenolic content in the juice was generally lower (p < 0.05) than in the cake. Polyphenols, flavonoids tannins, and anthocyanins were respectively the most quantitatively important compounds. On the other hand, the study of the antioxidant activity revealed that the cake had higher antioxidant activities.

Taken all together, the results showed that the cake of the C. edulis fruits has higher nutritional value, bioactive compound levels, and antioxidant potentials than juice which merits further consideration as food supplements.

In this century, viral infections are still a serious threat to the safety of human life and health. Millions of people were infected by viruses every year worldwide, and many of them died from the infections. In recent decades, outbreak pandemics of SARS, influenza, and especially SARS-Cov-2 (nCov-2019) have been witnessed. To protect people from viral infections, vaccine is one of the most important approaches. But to develop a vaccine against a viral infection, the status and its regulation of the human immunity against a viral infection must be explored and known well. As a reference for the protection approach or strategy to control viral infections, based on the reports or publications in recent years, we present our new perspectives about human immunity statuses against viral infection, and conclude the statuses as three basic types: efficient immunity status, non-efficient immunity status and separated immunity status.

Efficacy evaluations with preclinical magnetic resonance imaging (MRI) are uncommon, but MRI in the preclinical phase of drug development provides information that is useful for longitudinal monitoring. The study aim was to monitor the protective effectiveness of silymarin with multiparameter MRI and biomarkers in a thioacetamide (TAA)-induced model of liver injury in rats. Correlation analysis was conducted to assess compare the monitoring of liver function by MRI and biomarkers.

TAA was injected three times a week for 8 weeks to generate a disease model (TAA group). In the TAA and silymarin-treated (TAA-SY) groups, silymarin was administered three times weekly from week 4. MR images were acquired at 0, 2, 4, 6, and 8 weeks in the control, TAA, and TAA-SY groups.

The area under the curve to maximum time (AUCtmax) and T2* values of the TAA group decreased over the study period, but the serological markers of liver abnormality increased significantly more than those in the control group. In the TAA-SY group, MRI and serological biomarkers indicated attenuation of liver function as in the TAA group. However, pattern changes were observed from week 6 to comparable levels in the control group with silymarin treatment. Negative correlations between either AUCtmax or T2* values and the serological biomarkers were observed.

Silymarin had hepatoprotective effects on TAA-induced liver injury and demonstrated the usefulness of multiparametric MRI to evaluate efficacy in preclinical studies of liver drug development.

Hepatocellular carcinoma (HCC) is the fourth most common cause of cancer-related death and ranks sixth in terms of incident cases worldwide. The purpose of this study was to develop an effective and sensitive method to distinguish liver cancer tissues from normal tissues in HCC patients. Integrin α6 is a promising cell surface target for molecular imaging of HCC, where it is overexpressed and is a prognostic biomarker. We previously identified an integrin α6-targeted peptide CRWYDENAC (RWY) that has been used for positron emission tomography (PET) imaging of HCC in mouse models.

We labeled the integrin α6-targeted RWY peptide with cyanine 7 (Cy7) to form an optical probe (Cy7-RWY) for near infrared fluorescent (NIRF) and photoacoustic (PA) imaging in HCC. Mice transplanted with subcutaneous HCC-LM3 or orthotopic HCC-H22 cells that overexpressed integrin α6 were intravenously injected with Cy7-RWY and its corresponding Cy7-control. NIRF and PA images of mice were collected from 0 to 48 h after injection.

Both NIRF and PA signals started to accumulate in the tumor 2 h after injection of Cy7-RWY and peaked at 24 h.

Cy7-RWY is a promising optical probe for NIRF and PA imaging of HCC in mice, and has potential clinical application for HCC detection.

The aim was to evaluate the efficacy and safety of Yanggan Jian (YGJ) in HBV-infected patients with decompensated cirrhosis.

This randomized, double-blind controlled trial enrolled 160 patients with HBV-related decompensated cirrhosis who were already receiving or about to start antiviral therapy. Patients were randomly assigned to receive YGJ or placebo for 24 weeks, and were followed-up to 36 weeks. The primary outcome was the proportion of patients with a ≥2 point reduction in Child-Turcotte-Pugh (CTP) score from baseline at week 24. Secondary outcomes were CTP class and score, serum liver function indices, mortality, incidence of hepatocellular carcinoma and variceal bleeding.

The proportion of patients with a CTP score reduction ≥2 was significantly greater in the YGJ than in the placebo group (p=0.009); the percentage of patients with CTP class C was significantly less than that in the placebo group (p<0.05), and the YGJ group had a significantly greater mean change from baseline in CTP score at week 24 (p=0.034). The improvement in measured values and change from baseline of prothrombin time, serum albumin, platelets, cholinesterase, international normalized ratio, and activated partial thromboplastin time were significantly better with YGJ than with placebo. Between-group differences in cumulative rates of variceal bleeding, hepatocellular carcinoma, death, or the frequency of any adverse event (AE), AEs related to treatment, or discontinuation because of AEs were not significant.

YGJ significantly improved CTP scores and hepatic synthetic and reserve function in patients with HBV-related decompensated cirrhosis, and was safe and well tolerated.

After a period of more than 50 years, numerous evidences have led to the exploration of the cyclic control core of cells, which sequentially comprise of genomes (G), transcriptomes (T) and proteomes (P). In the previous reports of the investigators on spatiotemporal cell biology, a novel theory system was introduced and reported, and the cyclic control core was named, the “GTP core”. Indeed, the GTP core controls all events in cells based on the spatiotemporal cell biology. In the present study, the schematic regulation of the GTP core based on the spatiotemporal cell biology was further discussed and summarized, in order to improve and perfect this novel theory system. It is hoped that these perspectives would lead to the further discussion and exploration of this area by other researchers worldwide.

Liver organ shortage remains a major health burden in the US, with more patients being waitlisted than the number of liver transplants (LTs) performed. This study investigated US national and regional trends in living donor LT (LDLT) and identified factors associated with recipient survival.

We retrospectively analyzed LDLT recipients and donors from the United Network Organ Sharing/Organ Procurement Transplant Network database from 1998 until 2019 for clinical characteristics, demographic differences, and survival rate. National and regional trends in LDLT, recipient outcomes, and predictors of survival were analyzed.

Of the 223,571 candidates listed for an LT, 57.5% received an organ, of which only 4.2% were LDLTs. Annual adult LDLTs first peaked at 412 in 2001 but experienced a significant decline to 168 by 2009. LDLTs then gradually increased to 445 in 2019. Region 2 had the highest LDLT numbers (n=919), while region 1 had the highest proportion (11.1%). Overall, post-LT mortality was 21.4% among LDLT recipients. Post-LDLT survival rates after 1-, 5-, and 10-years were 92%, 87%, and 70%, respectively. Interval analysis (2004–2019) showed that patients undergoing LDLT in recent years had lower mortality than in earlier years (hazard ratio=0.81, 95% confidence interval=0.75–0.88).

Following a substantial decline after a peak in 2001, the number of adult LDLTs steadily increased from 2011 to 2019. However, LDLTs still constitute the minority of the transplant pool in the US. Life-saving policies to increase the use of LDLTs, particularly in regions of high organ demand, should be implemented.

Oropharyngeal squamous cell carcinomas (OPSCCs) have shown an alarming rate of increase in incidence over the past several decades, markedly in men. In the United States, transcriptionally-active human papillomavirus (HPV), particularly HPV 16, has become the highest contributive agent of OPSCCs, affecting approximately 16,000 people a year. Compared to patients with HPV-negative OPSCCs, patients with HPV-positive OPSCCs exhibit better health responses to chemoradiotherapy and an overall increase in long-term survival. Despite promising treatment options, many OPSCCs are discovered at an advanced stage, and ∼20% of cases will recur after definitive treatment. Therefore, extensive research is ongoing to identify new targets for precision treatment and to stratify tumor prognosis. The aim of this review is to capture the most updated research on HPV-positive OPSCCs, emphasizing their relevance as potential new targets for precision medicine and survival prognosis.

Euphorbiasteroid (EUP) is one of the ingredients of traditional Chinese medicinal plants with anti-inflammatory activity. This study aimed to evaluate the effect of EUP on rheumatoid arthritis (RA).

Cell Counting Kit-8 (CCK8) and 5-Ethynyl-2′-deoxyuridine (EdU) were performed to detect the proliferation of fibroblast-like synoviocytes (FLSs). The expression of cytokines was detected by quantitative real-time polymerase chain reaction (RT-qPCR) and enzyme-linked immunosorbent assay (ELISA). The Transwell system without the gel was utilized to detect the cell migration. The pro-angiogenesis ability of HUVECs was detected by tube formation assay. EUP was introduced into the collagen-induced arthritis (CIA) model to determine its therapeutic effect, as measured by microcomputed tomography (micro-ct) and hematoxylin-eosin (H&E) staining. AKT1 was enriched by network pharmacology and molecular docking techniques. Western blot, immunofluorescence (IF) and RT-qPCR were conducted to detect the effects of EUP on AKT1.

When RA FLSs were treated with EUP, the proliferation of RA FLSs decreased in a dose- and time-dependent manner. Furthermore, the production of inflammatory cytokines, cell migration and proangiogenic ability of RA FLSs were suppressed by the EUP treatment. The in vivo experiments revealed that EUP can significantly reduce the severity of the CIA model by decreasing the paw thickness, arthritis score, cartilage degeneration, joint destruction, and serum inflammatory cytokine level. The network pharmacology and molecular docking predicted AKT1 as the target, in which EUP exerts its effects. The western blot, IF and RT-qPCR identified the toll-like receptor signaling pathway and its key component, AKT1, as potential targets, in which EUP exerts its anti-arthritic effects in RA.

EUP ameliorates the deterioration of RA by inactivating the toll-like receptor signaling pathway via AKT1. Therefore, EUP might hold potential as a treatment medicine for RA.

Diabetic foot ulcers (DFUs) are a significant source of morbidity, and pose great financial burden to the health service. Conventional treatments with dressings are often ineffective. Platelet-rich products have been used in recent years for the treatment of DFUs, with promising results. The present study aims to evaluate the efficacy of plasma rich in growth factors (PRGF) membrane therapy in the treatment of chronic non-healing DFUs, in order to improve wound healing and accelerate the epithelisation of chronic wounds.

A total of six diabetic patients with chronic non-healing foot ulcers were included in the present study. The Endoret procedure was used to isolate the PRGF from blood samples, resulting in the formation of a membrane clot, which was placed over the bed of the ulcer. A portion of the PRGF was also allowed to infiltrate around the ulcer edge. Patients were followed up in clinic at two weekly intervals, until full healing was achieved.

All six patients (mean age: 60 years old) underwent successful treatment with the PGRF membrane. Full epithelisation of the ulcers was achieved for all patients, with a mean duration of eight weeks. No complications were noted throughout the treatment period.

The use of an autologous PRGF membrane is a secure and efficacious surgical treatment for chronic non-healing DFUs. The present study demonstrates that the PRGF fibrin membrane can be used to optimize surface regeneration in DFUs. Additional data and randomized studies are required to establish the effectiveness of this method in treating DFUs.

Nonalcoholic fatty liver disease (NAFLD) is a common chronic liver disease caused by over-nutrition. Impaired autophagy is closely related to NAFLD progression. Recently, ubiquitin-specific peptidase-10 (USP10) was reported to ameliorate hepatic steatosis, but the underlying mechanism is still unclear. In view of the potential effects of USP10 on autophagy, we investigated whether USP10 alleviated steatosis through autophagy.

HepG2 cells were treated with palmitic acid (PA) to model NAFLD in vitro. Lentivirus was used to regulate USP10 level in cells. Autophagic regulators were used to autophagic progression in cells. Western blotting, real-time fluorescence quantitative polymerase chain reaction, lipid drop staining and immunofluorescent staining were performed to determine the effect of USP10 on lipid autophagy. Student’s t-test and Tukey’s post hoc test were used to compare the means among groups.

PA induced cellular steatosis with dependance on autophagy. USP10 overexpression alleviated PA-induced steatosis, restored autophagic activity, promoted autophagic flux, including synthesis and degradation of autophagosomes, and lipid-targeted autophagy. In the presence of autophagy inhibitors, the protective effectiveness of USP10 on steatosis decreased. Furthermore, the specific inhibitor to C-jun N-terminal protein kinase-1 (JNK1), DB07268, abolished USP10-induced autophagy. However, during early stage inhibition of JNK1, compensatory expression of tuberous sclerosis complex-2 (TSC2) maintained autophagy. The degree of TSC2-to-JNK1 compensation was positively associated with USP10 level. Functionally, JNK1 and TSC2 were involved in the lipid-lowering effect of USP10.

USP10 alleviated hepatocellular steatosis in autophagy-dependent manner. JNK1/TSC2 signaling pathways were required for USP10-induced autophagy.

Liver stiffness (LS) measured by shear wave elastography (SWE) is often influenced by hepatic inflammation. The aim was to develop a dual-task convolutional neural network (DtCNN) model for the simultaneous staging of liver fibrosis and inflammation activity using 2D-SWE.

A total of 532 patients with chronic hepatitis B (CHB) were included to develop and validate the DtCNN model. An additional 180 consecutive patients between December 2019 and April 2021 were prospectively included for further validation. All patients underwent 2D-SWE examination and serum biomarker assessment. A DtCNN model containing two pathways for the staging of fibrosis and inflammation was used to improve the classification of significant fibrosis (≥F2), advanced fibrosis (≥F3) as well as cirrhosis (F4).

Both fibrosis and inflammation affected LS measurements by 2D-SWE. The proposed DtCNN performed the best among all the classification models for fibrosis stage [significant fibrosis AUC=0.89 (95% CI: 0.87–0.92), advanced fibrosis AUC=0.87 (95% CI: 0.84–0.90), liver cirrhosis AUC=0.85 (95% CI: 0.81–0.89)]. The DtCNN-based prediction of inflammation activity achieved AUCs of 0.82 (95% CI: 0.78–0.86) for grade ≥A1, 0.88 (95% CI: 0.85–0.90) grade ≥A2 and 0.78 (95% CI: 0.75–0.81) for grade ≥A3, which were significantly higher than the AUCs of the single-task groups. Similar findings were observed in the prospective study.

The proposed DtCNN improved diagnostic performance compared with existing fibrosis staging models by including inflammation in the model, which supports its potential clinical application.

Cardiac troponin T (cTnT) is independently associated with cardiovascular complications in patients with chronic kidney disease (CKD). The present study aimed to determine the factors related to cTnT levels in pre-dialysis CKD patients, which result in increased cardiovascular risk.

A total of 147 patients, with a mean age of 69.1 ± 14.7 years old, were enrolled. These participants were classified to estimated glomerular filtration rate (eGFR) and albuminuria categories, according to the Kidney Disease Improving Global Outcomes 2012 criteria. The estimated pulse wave velocity (ePWV), as an index of arterial stiffness, was calculated using an equation, which included age and mean blood pressure. Coronary arterial disease (CAD) and left ventricular hypertrophy (LVH) were also recorded. The cTnT concentrations were measured by high-sensitivity immunoassay. The significant correlation between cTnT and different variables was determined, and the significant risk factors for high cTnT levels were defined.

A significant correlation was observed between cTnT serum concentrations and age, triglycerides/HDL-C, ePWV, glucose, phosphate (P), intact-parathyroid hormone (i-PTH), serum uric acid and albuminuria, although the association with eGFR was shown to be significantly inverse. The multifactorial model revealed that current smoking (p = 0.03, OR = 8.3, 1.15–60.3), CAD (p = 0.001, OR = 25.2, 5.6–113.6), low eGFR (p = 0.001, OR = 0.9, 0.8–0.9), high ePWV (p = 0.04, OR = 2.6, 1.0–6.8), and primary renal disease (p = 0.001, OR = 3.8, 1.7–8.5) are independent risk factors for elevated cTnT levels, after adjusting for age, gender, obesity and albuminuria.

Arterial stiffness, smoking, primary renal disease and unregulated metabolic abnormalities may have an independent association between high cTnT levels and low eGFR in pre-dialysis CKD patients, with or without overt cardiovascular disease.

Natural killer (NK) cells are a gatekeeper of the body’s innate defense system against cancers and infections. A growing body of literature from us and others finds that NK cells promote anti-cancer immune surveillance, and that defects in NK cell development are associated with poor clinical prognosis of cancers. In preclinical studies, NK cells were found to drive tumor regression and delay tumor relapse. Because NK cells are potentially less damaging to the body and are easier to develop than T cell-based therapies, efforts are being made to improve NK cell cytotoxicity and in vivo persistence for use as an adoptive, off-the-shelf immunotherapy. In this review, we discuss how tumor-intrinsic and -extrinsic factors suppress NK cells in the cancer microenvironment. We also outline current strategies that restore NK surveillance in cancer and challenges facing the clinical use of NK cell-based therapies.

A considerable number of autoimmune hepatitis (AIH) patients completely or partially fail on first-line treatment. Several studies on the use of calcineurin inhibitors (CNIs) in the treatment of AIH have been published without focusing on indication. The aim was to assess the efficacy of CNIs in the treatment of adult AIH patients, specifically focusing on indication: first-line intolerant and with first-line insufficient response (failure to achieve or maintain remission), and with second versus third-line treatment.

A literature search included studies on the use of CNIs in adult AIH. Patients with past or present use of CNIs from the Dutch AIH group cohort were added. The primary endpoint was biochemical remission while using CNIs. Secondary endpoints were biochemical response, treatment failure, and adverse effects.

Twenty studies from the literature and nine Dutch patients were included describing the use of cyclosporine in 59 and tacrolimus in 219 adult AIH patients. The CNI remission rate was 53% in patients with insufficient response to first-line treatment and 67% in patients intolerant to first-line treatment. CNIs were used as second-line treatment in 73% with a remission rate of 52% and as third-line treatment in 22% with a remission rate of 26%. Cyclosporine was discontinued in 13% and tacrolimus in 11% of patients because of adverse events.

CNIs as rescue treatment in adult AIH patients are reasonably effective and safe both with insufficient response or intolerance to previous treatment. Prospective studies are needed.