Epigenetic-based combination therapy and liposomal codelivery overcomes osimertinib-resistant NSCLC via repolarizing tumor-associated macrophages.

Osimertinib (Osi) is widely used as a first-line treatment for non-small cell lung cancer (NSCLC) with EGFR mutations. However, the majority of patients treated with Osi eventually relapse within a year. The mechanisms of Osi resistance remain largely unexplored, and efficient strategies to reverse the resistance are urgently needed. Here, we developed a lactoferrin-modified liposomal codelivery system for the combination therapy of Osi and panobinostat (Pan), an epigenetic regulator of histone acetylation. We demonstrated that the codelivery liposomes could efficiently repolarize tumor-associated macrophages (TAM) from the M2 to M1 phenotype and reverse the epithelial-mesenchymal transition (EMT)-associated drug resistance in the tumor cells, as well as suppress glycolysis, lactic acid production, and angiogenesis. Our results suggested that the combination therapy of Osi and Pan mediated by liposomal codelivery is a promising strategy for overcoming Osi resistance in NSCLC.

Effect of Hepatic Artery Spasm on a Rat Model of Hepatic Ischemia-Reperfusion Injury.

OBJECTIVES: To investigate hemodynamic changes in the hepatic artery after hepatic ischemia-reperfusion injury (IRI) in rats via ultrasound (US) imaging and to discuss the protective effect of phentolamine (PHT) pretreatment on hepatic IRI. METHODS: Fifty rats were randomly divided into 3 groups: a sham operation group (n = 10), a control ischemia-reperfusion group (n = 20), and a PHT pretreatment group (n = 20). Color Doppler flow imaging and contrast-enhanced US examinations were performed in each group at 30 minutes (n = 10) and 90 minutes (n = 10) after reperfusion. Blood samples were obtained to analyze serum alanine aminotransferase and aspartate aminotransferase levels, and liver tissue specimens were collected for pathologic analysis. RESULTS: Using US, we found that hepatic artery resistance at 30 minutes after reperfusion in the control group was higher than that in the sham group (mean resistive index [RI] ± SD, 0.65 ± 0.09 versus 0.50 ± 0.09; P < .01), which was higher at 30 than 90 minutes (RI, 0.65 ± 0.09 versus 0.50 ± 0.08; P < .01) after reperfusion in the control group. However, the hepatic artery resistance and liver microcirculation in the PHT group were better than those in the control group at 30 minutes after reperfusion (RI, 0.54 ± 0.09 versus 0.65 ± 0.09; P < .05; time to peak, 31.94 ± 2.02 versus 48.34 ± 4.74 seconds; P < .01). Compared to the control group, the aspartate aminotransferase and alanine aminotransferase levels were significantly lower at 30 minutes after reperfusion in the PHT group (P < .05). A pathologic examination revealed a smaller hepatic artery diameter and a depressed vessel wall in the control group. CONCLUSIONS: The hepatic artery can undergo a transient spasm during the hepatic IRI process, which can exacerbate liver damage. Phentolamine treatment can alleviate hepatic artery spasms, improve liver perfusion, and reduce liver injury by ameliorating the hepatic microcirculation.

Preoperative Alfa-Fetoprotein and Fibrinogen Predict Hepatocellular Carcinoma Recurrence After Liver Transplantation Regardless of the Milan Criteria: Model Development with External Validation.

BACKGROUND/AIMS: Patient selection is critically important in improving the outcomes of liver transplantation for hepatocellular carcinoma. The aim of the current study was to identify biochemical measures that could affect patient prognosis after liver transplantation. METHODS: A total of 119 patients receiving liver transplantation for hepatocellular carcinoma were used to construct a model for predicting recurrence. The results were validated using an independent sample of 109 patients from independent hospitals. All subjects in both cohorts met the Hangzhou criteria. RESULTS: Analysis of the discovery cohort revealed an association of recurrence with preoperative fibrinogen and AFP levels. A mathematical model was developed for predicting probability of recurrence within 5 years: Y = logit(P) = -4.595 + 0.824 ×fibrinogen concentration (g/L) + 0.641 × AFP score (1 for AFP<=20ng/ml, 2 for 20 400ng/ml). At a cutoff score of -0.85, the area under the curve (AUC) was 0.819 in predicting recurrence (vs. 0.655 when using the Milan criteria). In the validation cohort, this model had reasonable performance in predicting 5-year overall survival (68.8% vs. 28.1% in using the -0.85 cutoff, p< 0.001) and disease-free survival (65.7% vs. 25.9%, p< 0.001). The sensitivity and specificity were 77.0% and 62.5%, respectively. The AUC of this newly developed model was similar to that with the Milan criteria (0.698 vs. 0.678). Surprisingly, the DFS in patients with score <= -0.85 under this model but not meeting the Milan criteria was similar to that in patients meeting the Milan criteria (53.8% vs. 60.0%, p=0.380). CONCLUSIONS: Preoperative AFP and fibrinogen are useful in predicting recurrence of hepatocellular carcinoma after liver transplantation.

Therapeutic potentials of umbilical cord-derived mesenchymal stromal cells for ischemic-type biliary lesions following liver transplantation.

BACKGROUND AIMS: Ischemic-type biliary lesions are severe, graft-threatening complications after orthotopic liver transplantation, and a novel and efficient therapeutic strategy is urgently needed. Due to the immunosuppressive and regenerative properties, mesenchymal stromal cells (MSCs) could be an interesting candidate. METHODS: We initiated safety and efficacy of human umbilical cord-derived MSC (UC-MSC) transfusions for patients with ischemic-type biliary lesions after liver transplantation. From January 2013 to June 2014, 12 ischemic-type biliary lesions patients were recruited as the MSCs group in this phase I, prospective, single-center clinical study. Patients in this group received six doses of UC-MSCs (about 1.0 × 106 MSCs per kilogram body weight through peripheral intravenous infusion). The traditional therapeutic protocol was applied during October 2003 to December 2012 in 70 ischemic-type biliary lesions patients who were treated as the control group. Liver function tests, the need for interventional therapies and graft survival rate were chosen to evaluate the therapeutic efficacy of MSC treatment. Adverse events were closely monitored up to 2 years after MSC transfusions. RESULTS: No significant MSC-related adverse events were observed during the trial. Compared with baseline, the levels of total bilirubin, γ-glutamyl transferase and alkaline phosphatase were decreased after UC-MSC treatment at week 20 and week 48. Interventional therapies were performed in 64.3% (45/70) of patients in the control group and 33.3% (4/12) of patients in the MSCs groups. MSC therapy significantly decreased the need for interventional therapies (P = 0.046). The 1- and 2-year graft survival rates were higher in the MSCs group (100% and 83.3%, respectively) than in the control group (72.9% and 68.6%, respectively). CONCLUSIONS: The UC-MSC transfusions are clinically safe and short-term favorable, which may become a novel treatment for patients with ischemic-type biliary lesions after liver transplantation.

Long-term results of liver transplantation for over 60 years old patients with hepatitis B virus-related end-stage liver disease.

BACKGROUND: Hepatitis B virus (HBV)-related end-stage liver disease is the leading indication for liver transplantation in China, but long-term results of liver transplantation in patients aged over 60 years are not clear. The present study was to reveal the natural history of liver recipients with hepatitis B older than 60 years. METHODS: The recipients who had received liver transplantation between December 2003 and December 2005 were divided into two groups: those equal or older than 60 years (older group, n=60) and those younger than 60 years (younger group, n=305). Risk factors for poor long-term outcome in patients aged over 60 years were also analyzed. RESULTS: Except for age and preexisting chronic disease (P<0.05), no significant differences were observed in perioperative characteristics between the two groups. There was also no significant difference in HBV and hepatocellular carcinoma recurrence (P>0.05). The actuarial 1-, 3-, 5- and 8-year survival rates were 81.6%, 71.6%, 66.7% and 63.3% respectively for the older group vs 84.9%, 77.7%, 70.8% and 65.6% for the younger group (P>0.05). Multivariate analyses showed that pre-liver transplant renal insufficiency was a risk factor for poor outcome in the older group (odds ratio=3.615, P=0.014). CONCLUSIONS: Liver transplantation is safe and feasible for patients with HBV-related end-stage liver disease aged over 60 years. Older patients with renal insufficiency should undergo transplantation earlier than younger patients.

A new fossil species of Meliolinites Selkirk associated with Rhodoleia leaves from the Upper Pliocene of southwestern China.

Fossil epifoliar fungi are valuable indicators of paleoenvironment and paleoecology. The Meliolaceae, members of which typically inhabit the surface of living plants as biotrophs or pathogens, is one of the largest groups of epifoliar fungi. In this study, we report a novel fossil species of Meliolinites Selkirk (fossil Meliolaceae), Meliolinites tengchongensis, on the lower epidermis of compressed fossil Rhodoleia (Hamamelidaceae) leaves from the Upper Pliocene Mangbang Formation of Tengchong, Yunnan, southwestern China. Meliolinites tengchongensis is characterized by web-like, superficial, brown to dark brown, septate, and branching mycelia bearing 2-celled appressoria and unicellular phialides. The fungal colonies also include ellipsoidal, 5-celled, 4-septate ascospores and dark brown perithecia with suborbicular outline and verrucose surface. The well-preserved vegetative and reproductive organs help us to explore the potential disease process of the new fossil species. Besides, the presence of fungal remains indicates that the fungal taxon might have maintained its host preference since at least the Late Pliocene. Furthermore, the occurrence of both fossil fungi and their host plants in Tengchong indicate a subtropical-tropical, warm, and humid climate during the Late Pliocene, whereas the distribution pattern of the fungi on the host leaves suggests that Rhodoleia may have been a part of the middle-upper canopies in the Tengchong Late Pliocene multilayered forest.

Physicochemical characteristics of grease-trap wastewater with different potential mechanisms of FOG solid formation, separation, and accumulation inside grease traps.

This work investigates the physicochemical characteristics of grease-trap wastewater discharged from a large community market. It proposes potential mechanisms of fat, oil, and grease (FOG) solid formation, separation, and accumulation inside grease traps. Sixty-four samples, i.e., the floated scum, suspended solid-liquid wastewater, and settled sludge, were collected from the grease-trap inlet and outlet chambers. A lower pH of 5-6 at 25-29 °C inside the grease trap than those reported under the sewer conditions (pH 6-7) was revealed. A significant difference in solid and dissolved constituents was also discovered between the inlet and outlet chambers, indicating that the baffle wall could affect the separation mechanism. The sludge samples had 1.5 times higher total solids (TS) than the scum samples, i.e., 0.225 vs. 0.149 g g-1 TS, revealing that the sludge amount impacted more significantly the grease trap capacity and operation and maintenance. In contrast, the scum samples had 1.4 times higher volatile solids (VS) than the sludge samples, i.e., 0.134 vs. 0.096 g g-1 VS, matching with the 64.2 vs. 29.7% of carbon content from CHN analysis. About 2/3 of the free fatty acids (FFAs) with palmitic acids were the primary saturated FFAs, while the remaining 1/3 of unsaturated FFAs were found in the solid and liquid samples. Although up to 0.511 g g-1 FOG can be extracted from the scum samples, none from the sludge samples. More diverse minerals/metals other than Na, Cl, and Ca were found in the sludge samples than in the scum samples. Grease-trap FOG solids and open drain samples exhibited similar physicochemical properties to those reported in the literature. Four potential mechanisms (crystallization, emulsification, saponification, and baffling) were presented. This work offers insights into the physicochemical properties of grease-trap wastewater that can help explore its FOG solid formation, separation, and accumulation mechanisms inside a grease trap.

Indirect comparison of anti-TNF-α agents for active ankylosing spondylitis: mixed treatment comparison of randomized controlled trials.

OBJECTIVES: We aimed to identify different anti-TNF-α agents for ankylosing spondylitis (AS) assessed in randomised controlled trials (RCTs) and to compare them within a single evidence synthesis framework. METHODS: A Bayesian network analysis method was used to generate direct and indirect comparisons while maintaining randomisation. The main outcomes were the proportion of ASAS20 patients at the follow-up of 12 weeks. The analysis was made based on an intention-to-treat basis. RESULTS: Data were combined from 14 (RCTs) that included 17833 patients randomised to 7 treatment strategies, including placebo. Except for 3mg/kg infliximab at 0, 2, 6 weeks, all other treatments were demonstrated to be more effective than placebo in the terms of clinical index ASAS20. Compared with 25 mg etanercept twice a week, 50 mg etanercept once a week, 50 mg golimumab, 100 mg golimumab every four weeks, 5mg/kg infliximab at 0, 2, 6 weeks and 40 mg adalimumab every other week for 12 weeks seemed to be more effective (odds ratios [OR] 1.38, 1.22, 1.26, 1.29, 1.38, and 1.25, respectively), while etanercept 50 mg twice a week have the similar efficacy (odds ratios [OR] 1.08), and infliximab 3 mg/kg at 0, 2, 6 weeks was less effective (odds ratios [OR] 0.69). However, all of these between-treatment comparisons detected no significant analysis. Finally, ranking analysis suggested that infliximab 5 mg/kg at 0, 2, 6 weeks may be the best efficacious therapy. CONCLUSIONS: Our results suggested that infliximab 5 mg/kg at 0, 2, 6 weeks seems to be the best efficacious therapy, while infliximab 3 mg/kg at 0, 2, 6 weeks maybe could not be considered in the future studies. Future studies could pay more attention to the comparison of different anti-TNF agents, instead of comparison between anti-TNF agents and placebo.

Pagoda[n]arenes (n = 4, 5): Extremely Strong Binders for the Tropylium Cation.

Herein, host-guest complexation between pagoda[n]arenes (n = 4, P4; n = 5, P5) and tropylium cation (G) was investigated in detail. It was found that both P4 and P5 showed surprisingly strong binding affinities toward the tropylium cation with association constants of more than 107 M-1 for the 1:1 host-guest complexes. The theoretical calculations showed different host-guest complexion ways for complexes G@P4 and G@P5 and the strong π···π interactions and multiple C-H···π interactions play a very important role in the formation of these stable complexes, respectively. Moreover, the switchable processes of guest binding and release in the complexes can be effectively controlled by redox stimuli, and they can be also visible by the color and fluorescence changes.

Coumarin-cyanine hybrid: A ratiometric fluorescent probe for accurate detection of peroxynitrite in mitochondria.

There is an urgent need to develop highly sensitive and selective fluorescence probes for ONOO- in mitochondria. Herein, we reported a ratiometric fluorescent probe COUS with coumarin-cyanine hybrid as fluorophore and C = C bonds as reaction sites of ONOO-. The probe COUS was sensitive and selective to ONOO-, and had a large fluorescence emission shift (239 nm) as well as a low detection limit (41.88 nM). Moreover, COUS showed the mitochondrial targeting ability, and the targeting moiety could dissociate from the probe when reacting with ONOO-, which enabled COUS to accurately detect ONOO- in mitochondria.

Complexation with pagoda[n]arene (n = 4, 5) protects ferrocenium from oxidation.

The complexation behaviors of pagoda[n]arenes (n = 4, 5) with ferrocene, ferrocenium and analogues cobaltocenium were studied. The inclusion complexes of pagoda[n]arenes can protect ferrocenium from oxidation in organic solvents and improve the stability and oxygen resistance of ferrocenium.

Bone marrow mesenchymal stem cells ameliorate hepatic ischemia/reperfusion injuries via inactivation of the MEK/ERK signaling pathway in rats.

BACKGROUND: Primary graft dysfunction or nonfunction after liver transplantation, which is usually caused by ischemia/reperfusion injury (IRI), is a serious clinical problem. Although bone marrow mesenchymal stem cells (MSCs) have shown great potential in cell therapy for IRI in several organs, the mechanism(s) by which MSCs offer protection is unclear. METHODS: In the present study, we injected MSCs systemically via the tail vein in the rat model of 70% hepatic IRI and measured the biochemical and pathologic alterations to evaluate the therapeutic effect of MSC transplantation. Concurrently, H(2)O(2) was used in vitro to mimic oxidative injury and to induce apoptosis in the human normal liver cell line LO2 to evaluate the protective effects of mesenchymal stem cell conditioned medium (MSC-CM) on LO2 cells. RESULTS: The systemic infusion of MSCs led to a significant prevention of liver enzyme release and an improvement in the histology of the acutely injured liver. In vitro assays demonstrated that MSC-CM promoted hepatocyte proliferation and had a direct inhibitory effect on hepatocyte apoptosis induced by H(2)O(2). In addition, we demonstrated that the prevention of MEK/ERK pathway activation played a pivotal role in the protection. CONCLUSIONS: These data suggest that MSC may represent a potential therapeutic strategy to alleviate hepatic ischemia/reperfusion injuries after liver transplantation via inactivation of the MEK/ERK signaling pathway.

Clinical study on prevention of HBV re-infection by entecavir after liver transplantation.

PURPOSE: This aims to evaluate the effects of lamivudine (LAM) and entecavir (ETV) in preventing hepatitis B virus (HBV) re-infection after liver transplantation (LT). METHODS: A retrospective matched case-control method was used in this study. From June 2005 to May 2007, the patients who received LAM (100 mg qd) or ETV (0.5 mg qd) were chosen. The LAM and ETV groups were matched using a 3:1 ratio based on the factors, such as age, gender, LAM or ETV antiviral duration, primary disease, and HBV DNA levels at the initiation of antiviral therapy. Data on serum HBV markers, HBV DNA, and cumulative recurrence were collected. RESULTS: Two hundred and fifty-two patients were enrolled. The average duration of follow-up was 38.5 and 41.2 months (LAM and ETV groups) (p>0.05). Duration of pre-operative antiviral therapy was 30.3 and 25.8 d (LAM and ETV groups) (p>0.05). The HBV DNA level decreased from 3.89×10(6) to 5.31×10(5) copies/mL before LT in the LAM group, and decreased from 8.74×10(6) to 5.49×10(4) copies/mL in the ETV group (p<0.05). Eighteen patients in LAM group developed HBV re-infection and 0 in ETV group. CONCLUSION: ETV is superior to LAM for preventing HBV re-infection following LT.

Health-related quality of life after liver transplantation: the experience from a single Chinese center.

BACKGROUND: Few studies have been performed to assess health-related quality of life (HRQOL) in liver transplantation (LT) patients in the mainland of China. This study aimed to investigate the HRQOL of post-LT patients in a single center. METHODS: HRQOL was evaluated by the SF-36 (Chinese version) questionnaire in 60 patients (LT group) who had received LT for benign end-stage liver disease (BELD). Fifty-five patients with BELD (BELD group) and 50 healthy volunteers from the general population (GP group) were also evaluated, and the results were compared among the three groups. RESULTS: There was a significant difference among the three groups in terms of the scores of eight domains in the SF-36 (P<0.01). Patients in the BELD group had lower scores in each domain of the SF-36 in comparison with those in the GP group (P<0.025). The LT group had mental health scores equivalent to those of the BELD group (P>0.025), but higher scores for the remaining seven domains (P<0.025). Compared with the GP group, the LT group scored equivalently for role physical, body pain, vitality, social function and role emotion (P>0.025), but had lower scores for the remaining three domains (P<0.025). Lower family income was found to be associated with reduced physical function and mental health scores (P<0.05). Better education was associated with increased mental health scores (P<0.05). CONCLUSIONS: LT patients generally have a good HRQOL although some respects of their HRQOL remains to be improved. Lower family income and poor education are important factors relating to the poor HRQOL of LT patients.

Rapamycin combined with allogenic immature dendritic cells selectively expands CD4+CD25+Foxp3+ regulatory T cells in rats.

BACKGROUND: Dendritic cells (DCs) can initiate the expansion of regulatory T cells (Tregs), which play an indispensable role in inducing transplantation tolerance. Some studies have investigated the effect of the immunosuppressant rapamycin (Rapa) on Tregs in vitro. However, the in vivo effect of Rapa combined with immature DCs (iDCs) on Tregs is unknown. This study was undertaken to determine whether allogenic iDCs combined with a short course of Rapa have the ability to selectively expand the CD4+CD25+Foxp3+ Tregs in a rat model. METHODS: Brown Norway rats were injected intravenously with 2X10(6) Lewis iDCs followed by 1 mg/kg per day Rapa intraperitoneally for 7 consecutive days. On day 8, the levels of CD4+CD25+Foxp3+ Treg cells in peripheral blood and spleen cells were analyzed by flow cytometry. IL-2, IL-4, TGF-beta1, and IFN-gamma levels in serum were assessed by ELISA. The experimental animals were divided into four groups: control, Rapa-treated, iDC-treated, and combination-treated. RESULTS: CD4+CD25+Foxp3+ Tregs comprised 7%-8% of CD4+ T cells in control rats. Rapa combined with iDCs enhanced this percentage in the peripheral blood and spleen. However, the levels of Tregs did not significantly change after treatment with Rapa or iDCs alone. The levels of CD4+CD25-Foxp3+ T cells and CD4+CD25+Foxp3- T cells in CD4+ T cells did not significantly change in the combined group. The TGF-beta1 level in serum from the combined group increased significantly compared with the other groups. CONCLUSIONS: A significantly higher percentage of CD4+ CD25+ Foxp3+ Tregs was found in rats treated with allogenic iDCs and a short course of Rapa, along with an increase in the TGF-beta1 level in serum. This improved protocol may be a promising therapeutic strategy to increase Tregs, which are beneficial to the induction of peritransplant tolerance.

[Alterations of immune status in liver transplant patients with sepsis].

OBJECTIVE: To explore the alterations of immune status in liver transplant recipients with sepsis so as to provide rationales for the adjustments of immunosuppressive agents. METHODS: A total of 47 cases complicated with sepsis after abdominal operations from January 2009 to December 2010 were divided into 4 groups according to the type of operations and the stage of sepsis: A. sepsis after transplantation (TS, n = 11), B. severe sepsis after transplantation (TSS, n = 10), C. sepsis without transplantation (NTS, n = 15) and D. severe sepsis without transplantation (NTSS, n = 11). Ten healthy volunteers were selected as the control group. Blood samples were collected from these patients to measure the immunological parameters associated with T lymphocyte. RESULTS: The APACHII and SOFA score of TSS group and NTSS group were both higher than TS group and NTS group respectively (all P < 0.01). In addition, SOFA score in TSS group was significantly higher than that in NTSS group (17.0 ± 4.5 vs 12.1 ± 2.8, P < 0.01). The percentages of T cell in 4 groups were all significantly lower than healthy volunteers (all P < 0.01). The CD4/CD8 ratio was slightly lower in the TSS group than those in the control group and the other three groups (P = 0.095). As compared with the control group, the IFN-γ/IL-4 ratios were significant lower in the TSS and NTSS groups (0.039 ± 0.012, 0.047 ± 0.018 vs 0.062 ± 0.006) while the level of IL-10 was higher ((32.6 ± 7.5), (25.9 ± 4.3) vs (8.2 ± 1.4) ng/L, all P < 0.05). And the difference was more significant in the TSS group. As compared with the healther, the percentage of CD4(+)CD25(+)Foxp3(+)Treg was lower in NTS group (2.21% ± 0.96% vs 4.06% ± 0.52%, P < 0.01), and significantly higher in NTSS group (8.02% ± 3.57% vs 4.06% ± 0.52%, P = 0.003). No significant difference existed in the percentage of Treg between the TS and control groups (P = 0.398). And it was significantly higher that in the TSS group (5.16% ± 0.99% vs 4.06% ± 0.52%, P = 0.006). But the magnitude of increase level was not so great as that in the NTSS group. The changes of Foxp3 mRNA demonstrated the similar trend as the percentage of Treg. CONCLUSIONS: The immune states of transplant recipients with sepsis are comparable with healthy persons during sepsis. It may subsequently develop into serious immunosuppression. Immunosuppressant should be withdrawn in severe sepsis stage so as to reconstitute the immune system.

[Reproduction after liver transplantation: a report of 13 cases from a single Chinese center].

OBJECTIVE: To explore the recipient's reproduction after liver transplantation (LT) and assess the outcomes of their offspring. METHODS: We retrospectively analyzed the reproduction status of 13 post-LT patients among 336 post-LT recipients during a follow-up period. Physical and intellectual status of their offspring were evaluated by developmental index and Denever developmental screening test. RESULTS: A total of 16 children were mothered or fathered by 13 LT patients. Two female patients mothered a boy and a girl. Ten male patients fathered 6 male and 8 female children while another male fathered a child at 28 gestational weeks. Eleven patients fathered the first gestation 21 mon (medium) since LT, and fathered 15 pregnancies. Twelve of 14 deliveries had a mean gestation age of (38.2 ± 1.8) weeks, with a mean birth weight of (3.1 ± 0.5) kg. Among 12 newborns, 3 were premature and 2 of a low birth weight. Two female patients delivered 2 babies with a gestation age of 37.3 and 40.4 weeks, a birth weight of 2.7 and 3.4 kg, and anoxia neonatorum in one case. No deformity was found. Thirteen of 16 children had almost normal developmental indices and ten had almost normal Denever developmental screening. CONCLUSION: Post-LT patients of reproductive age are able to reproduce offspring. The short-term development of their offspring is relatively normal.

Mindfulness Affects the Level of Psychological Distress in Patients With Lung Cancer via Illness Perception and Perceived Stress: A Cross-Sectional Survey Study.

Purpose: The aims of the study were first to investigate the association between illness perception and psychological distress and second to determine whether mindfulness affects psychological distress via illness perception and perceived stress in patients with lung cancer. Methods: Among 300 patients with lung cancer who participated in this cross-sectional study, 295 patients made valid responses to distress thermometer (DT), the Five Facet Mindfulness Questionnaire (FFMQ), the Brief Illness Perception Questionnaire (B-IPQ), and the Perceived Stress Scale (PSS) between January and July 2021. The possible pathways of mindfulness affecting psychological distress were analyzed based on the structural equation modeling analysis. Results: A total of 24.4% patients with lung cancer had DT > 4. Illness perception (ß = 0.17, p = 0.002) and perceived stress (ß = 0.23, p < 0.001) had a direct effect on psychological distress. Mindfulness had a direct effect on illness perception (ß = -0.16, p = 0.006) and mindfulness indirectly influenced psychological distress (ß = -0.04, p = 0.009) through affecting illness perception alone or simultaneously affecting both the illness perception and perceived stress in patients with lung cancer. Conclusion: Lung cancer suffered from varying levels of psychological distress. Mindfulness may alleviate psychological distress by reducing the level of illness perception and perceived stress. We suggest developing a comprehensive factor model to clarify potential mechanisms of mindfulness on psychological distress due to the very low effect of mindfulness on psychological distress via illness perception and perceived stress.

The Impact of Mindfulness-Based Stress Reduction (MBSR) on Psychological Outcomes and Quality of Life in Patients With Lung Cancer: A Meta-Analysis.

Objective: The impact of the mindfulness-based stress reduction (MBSR) program on psychological outcomes and quality of life (QoL) in lung cancer patients remains unclear. This meta-analysis aimed to evaluate the effectiveness of the MBSR program on psychological states and QoL in lung cancer patients. Methods: Eligible studies published before November 2021 were systematically searched from PubMed, EMBASE, Cochrane Library, PsycINFO, China National Knowledge Infrastructure (CNKI), and Wanfang databases. The risk of bias in eligible studies was assessed using the Cochrane tool. Psychological variables and QoL were evaluated as outcomes. We used the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system to grade the levels of evidence. Statistical analysis was conducted using RevMan 5.4 and STATA 14.0. Results: A total of 17 studies involving 1,680 patients were included for meta-analysis eventually. MBSR program significantly relieved cancer-related fatigue (standard mean difference [SMD], -1.26; 95% confidence interval [CI], -1.69 to -0.82; moderate evidence) and negative psychological states (SMD, -1.35; 95% CI, -1.69 to -1.02; low evidence), enhanced positive psychological states (SMD, 0.91; 95% CI, 0.56-1.27; moderate evidence), and improved quality of sleep (MD, -2.79; 95% CI, -3.03 to -2.56; high evidence). Evidence on MBSR programs' overall treatment effect for QoL revealed a trend toward statistical significance (p = 0.06, low evidence). Conclusion: Based on our findings, the MBSR program shows positive effects on psychological states in lung cancer patients. This approach should be recommended as a part of the rehabilitation program for lung cancer patients. Systematic Review Registration: https://archive.org/details/osf-registrations-mwvbq-v1, identifier: 10.17605/OSF.IO/MWVBQ.

Association of phenotypic transformation of circulating tumor cells and early recurrence in patients with hepatocellular carcinoma following liver transplantation.

BACKGROUND: CTCs play a critical role in the diagnosis and prognosis of liver cancer. However, there are few studies on whether different types of CTCs can predict the prognosis in patients with HCC following LT. METHODS: Retrospective data including CTCs detected by the CanPatrolTM platform combined with RNA-ISH were collected and analyzed on 56 patients from December 2016 to December 2019 at the Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong Province, China. RESULTS: During the study period, fifty-six patients (51 males, 5 females) were included with an mean age of 52 ± 9 years. The 1-, 2- and 3-year recurrence rates of postoperative interstitial CTC-positive and CTC-negative groups were 21.7% vs 10.8%, 37.5% vs 10.8% and 55.5% vs 10.8%, confirming a statistically significant difference between the 2 groups (p = 0.044). The 1-, 2- and 3-year recurrence rates of the increasing interstitial CTCs group were 25.2%, 36.9% and 66.9%, while 12.6%, 24.4% and 24.4% in the decreasing and unchanged group, indicating a significant difference (p = 0.038). CONCLUSION: CanPatrolTM platform presents a superior analytical sensitivity, and may be used as a dynamic monitoring tool for CTCs. And interstitial CTCs which are more aggressive and metastatic caused by EMT can be regarded as a predictor of post-transplant tumor recurrence after LT for HCC.