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Background Lung adenocarcinoma (LUAD) is a more frequent subtype of lung cancer and most cases are discovered in the late stages. The proliferation and metastasis of LUAD are pivotal for disease progression. Despite unremitting deeper understanding of LUAD biology, the mechanisms involved in the proliferation and metastasis of LUAD remain unclear. The objective of our article was to inquiry the expression and the function of keratin 6C (KRT6C) in LUAD cells. Methods First, the expression level and prognostic value of KRT6C in LUAD tissues were analyzed on the basis of the data acquired from TCGA database. Through qRT-PCR, the expression level of KRT6C on LUAD cell lines (A549, H1299, PC-9) and human normal lung cell line MRC-5 was tested. After that, CCK8 and colony formation assays was utilized to detect cell proliferation. In addition, to explore the influence of KRT6C on LUAD migration and invasion ability, scratch wound healing and transwell assays were utilized. Through western blotting, the protein expression levels of KRT6C, PCNA, E-cadherin, N-cadherin, Snail and Vimentin were detected. Results The outcomes revealed that KRT6C was highly expressed in LUAD tissues and cell lines. Besides, elevated level of KRT6C was related to worse prognosis in LUAD patients. Ablation of KRT6C restrained proliferation, migration and invasion of A549 cells. KRT6C deficiency augmented the expression of E-cadherin as well as reduced the expression of N-cadherin, Snail and Vimentin. Conclusion Above all, these consequences indicated that depletion of KRT6C suppressed A549 cell proliferation, migration and invasion, which might be achieved by regulating EMT. In general, KRT6C is identified as a potential therapeutic target for LUAD.

Aim： To investigate the safety, tolerability and pharmacokinetics of intravenous hemoporfin, a novel photosensitive drug for the treatment of port-wine stain （PWS）, in healthy Chinese volunteers following single-dose administration. Methods： Thirty-six healthy Chinese subjects were enrolled. The subjects were administered hemoporfin （2.5, 5, 7.5 or 10 mg/kg） via single-dose intravenous infusion. Pharmacokinetics of the drug were studied in the groups with doses of 2.5, 5 and 7.5 mg/kg, and tolerability was studied in all the 4 groups. Safety and tolerance were evaluated by monitoring adverse events and laboratory parameters, and pharmacokinetics were assessed by determining hemoporfin content with a validated high-performance liquid chromatography with fluorescence detection （HPLC/FLD） method. Results： Mild and transient adverse events occurred in the trial （n=10）, but none were serious, and no subjects were withdrawn from the trial. The gastrointestinal tract adverse events, such as nausea, stomach upset, abdominal pain and vomiting, were observed in the groups with doses of 7.5 and 10 mg/kg. Increased alanine aminotransferase （ALT） concentration was found in 3 subjects, and increased alkaline phosphatase （ALP） concentration in one subject. The ha~f-life of hemoporfin for doses of 2.5, 5, and 7.5 mg/kg was 1.26 h, 1.31 h, and 1.70 h, respectively. Cmax and AUC increased with dose for intravenous single-dose administration of hemoporfin in the 2.5, 5, and 7.5 mg/kg groups. Urinary excretion of hemoporfin within 12 h was less than 0.2%. Conclusion： Hemoporfin is safe and well-tolerated in healthy Chinese volunteers at a single intravenous dose of up to 10 mg/kg. It was rapidly cleared from the blood and had a short half-life, which insures a short light-avoidance period.

Owing to their brittleness and heterogeneity, achieving carbon fiber-reinforced silicon carbide ceramic (C f /SiC) composites with ideal dimensional and shape accuracy is difficult. In this study, unidirectional C f materials were subjected to orthogonal grinding experiments using different fiber orientations. Through a combined analysis of the surface morphology and grinding force after processing, the mechanism underlying the effect of the fiber orientation on the surface morphology of the material was explained. The surface roughness of the material was less affected by the process parameters and fluctuated around the fiber radius scale; the average surface roughness ( R a ) in the direction of scratching parallel (SA) and perpendicular (SB) to the fiber direction was 4.21‒5.00 μm and 4.42‒5.26 μm, respectively; the material was mainly removed via the brittle removal mechanism; and the main defects of the fiber in the SA direction were tensile fracture and extrusion fracture; the main defects of the fiber in the SB direction were bending fracture, shear fracture, and fiber debonding. The grinding parameters influenced the grinding force in the order: depth of cut > feed rate > wheel speed. The grinding force increased with an increase in the feed rate or depth of cut and decreased with an increase in the wheel speed. Moreover, increasing the depth of cut was more effective in decreasing the grinding force and improving the material removal efficiency than adjusting the rotational speed of the workpiece and the rotational speed of the grinding wheel. The specific grinding energy decreased with an increase in the feed rate or depth of cut, and increased with an increase in the grinding wheel speed.

The role of B7‐H3 in acute myeloid leukemia (AML) is not fully understood. Two previous studies investigating its expression and significances in AML are partially different. In this study, we aimed to systematically characterize the genomic and immune landscape in AML patients with altered B7‐H3 expression using multi‐omics data in the public domain. We found significantly increased B7‐H3 expression in AML compared to either other hematological malignancies or healthy controls. Clinically, high B7‐H3 expression was associated with old age, TP53 mutations, wild‐type WT1 and CEBPA, and the M3 and M5 FAB subtypes. Moreover, we observed that increased B7‐H3 expression correlated significantly with a poor outcome of AML patients in four independent datasets. Gene set enrichment analysis (GSEA) revealed the enrichment of the “EMT” oncogenic gene signatures in high B7‐H3 expressers. Further investigation suggested that B7‐H3 was more likely to be associated with immune‐suppressive cells (macrophages, neutrophils, dendritic cells, and Th17 cells). B7‐H3 was also positively associated with a number of checkpoint genes, such as VISTA (B7‐H5), CD80 (B7‐1), CD86 (B7‐2), and CD70. In summary, we uncovered distinct genomic and immunologic features associated with B7‐H3 expression in AML. This may lead to a better understanding of the molecular mechanisms underlying B7‐H3 dysregulation in AML and to the development of novel therapeutic strategies. In this paper, we found significantly increased B7‐H3 expression in AML compared to either other hematological malignancies or healthy controls. Importantly, we observed that increased B7‐H3 expression correlated significantly with a poor outcome of AML patients in four independent datasets. We also uncovered distinct genomic and immunologic features associated with B7‐H3 expression in AML.

Dual kidney transplantation (DKT) from small pediatric donors, either en-bloc or split dual kidney transplantation, contributes to mitigating organ scarcity. This study investigates the prognosis of DKT from pediatric deceased donors, and influencing factors. A retrospective study included recipients who underwent DKT from pediatric donors between 2012 and 2022. Recipients were categorized into low mismatch (BWLM,  = 30) and high mismatch (BWHM,  = 10) groups based on donor-recipient weight ratio of 1:10. Outcome encompassed recipient and graft survival, renal function, and adverse events. Forty recipients were included. The average follow-up period was 54.6 months. The 1, 3, and 5-year patient survival were 97.4%, with no significant differences between en-bloc and split dual kidney transplantation or between BWLM and BWHM groups. The graft survival at 1, 3, and 5 years were 89.9%, the graft survival of BWHM group was lower than BWLM group (70% vs 96.7%,  = 0.039). The average eGFR at 1, 3, and 5 years postoperatively were (78.93 ± 25.23), (83.82 ± 32.4), and (85.92 ± 37.08) mL/min/1.73 m , respectively. The BWHM group also experienced higher rates of graft-related surgical complications (  = 0.006) and urinary tract surgical complications (  = 0.042). DKT from pediatric donors yields favorable outcomes, with similar graft survival and complication rates across surgical subgroups. However, significant donor-recipient weight mismatch, particularly when the ratio is less than 1:10, may contribute to increased surgical complications and poorer graft survival. Efforts to minimize extreme weight mismatch are recommended to optimize outcomes.

Background We screened out several hypermethylated solute carrier (SLC) family genes in acute myeloid leukemia by reduced representation bisulfite sequencing. SLC22A3 encodes an organic cation transport protein, which is critical for drug transportation and cellular detoxification. SLC22A3 is significantly downregulated and associated with tumor progression and worse prognosis in a variety of solid tumors. However, there are no data available regarding the role of SLC22 in AML. This study aimed to explore the regulatory mechanism of DNA methylation on SLC22A3 expression, as well as its clinical significance in AML prognosis. Results SLC22A3 was identified as the sole prognosis-associated gene among SLCs based on TCGA and Beat AML databases. Bone marrow mononuclear cells (BMMNCs) from AML, MDS patients, and healthy donors were enrolled in this study. SLC22A3 methylation was significantly increased in AML compared with controls and MDS patients; meanwhile, the expression level of SLC22A3 was decreased. SLC22A3 hypermethylation presented an obvious association with some specific clinical characteristics and affected the survival time of AML patients as an independent risk indicator. SLC22A3 expression changed regularly as the disease complete remissions and relapses. Demethylation drug 5-aza-2′-deoxycytidine (DAC) activated transcription and increased mRNA expression of SLC22A3 in leukemia cell lines and AML fresh BMMNCs. Knockdown of SLC22A3 in leukemia cells enhanced cell proliferation and suppressed cell apoptosis. Data from public programs were used for auxiliary screening of probable molecular mechanisms of SLC22A3 in the antileukemia effect. Conclusions Our results showed that increased methylation and decreased expression of SLC22A3 may be indicators of poor prognosis in AML. Methylation-silenced SLC22A3 expression may have potential guiding significance on antileukemia effect of DAC.

Objective To identify topics attracting growing research attention as well as frontier trends of acupuncture-neuroimaging research over the past two decades. Methods This paper reviewed data in the published literature on acupuncture neuroimaging from 2000 to 2020, which was retrieved from the Web of Science database. CiteSpace was used to analyze the publication years, countries, institutions, authors, keywords, co-citation of authors, journals, and references. Results A total of 981 publications were included in the final review. The number of publications has increased in the recent 20 years accompanied by some fluctuations. Notably, the most productive country was China, while Harvard University ranked first among institutions in this field. The most productive author was Tian J with the highest number of articles (50), whereas the most co-cited author was Hui KKS (325). Evidence-Based Complementary and Alternative Medicine (92) was the most prolific journal, while Neuroimage was the most co-cited journal (538). An article written by Hui KKS (2005) exhibited the highest co-citation number (112). The keywords “acupuncture” (475) and “electroacupuncture” (0.10) had the highest frequency and centrality, respectively. Functional magnetic resonance imaging (fMRI) ranked first with the highest citation burst (6.76). Conclusion The most active research topics in the field of acupuncture-neuroimaging over the past two decades included research type, acupoint specificity, neuroimaging methods, brain regions, acupuncture modality, acupoint specificity, diseases and symptoms treated, and research type. Whilst research frontier topics were “nerve regeneration”, “functional connectivity”, “neural regeneration”, “brain network”, “fMRI” and “manual acupuncture”.

ObjectiveTo evaluate the efficacy and safety of Tongxiening Granules (痛泻宁颗粒, TXNG) in the treatment of irritable bowel syndrome with predominant diarrhea (IBS-D).MethodsA randomized, double-blind, double-dummy, and positive parallel controlled clinical trial was conducted from October 2014 to March 2016. Totally 342 patients from 13 clinical centers were enrolled and randomly assigned (at the ratio of 1:1) to a treatment group (171 cases) and a control group (171 cases) by a random coding table. The patients in the treatment group were administered orally with TXNG (5 g per time) combined with pinaverium bromide Tablet simulator (50 mg per time), 3 times per day. The patients in the control group were given TXNG simulator (5 g per time) combined with pinaverium bromide Tablets (50 mg per time), 3 times per day. The treatment course lasted for 6 weeks. The improvement of Irritable Bowel Syndrome Symptom Severity Score (IBS-SSS) was used to evaluate the primary outcome. Secondary outcomes included adequate relief (AR) rate, Irritable Bowel Syndrome-Quality of Life Questionnaire (IBS-QOL), Hamilton Anxiety Scale (HAMA), Hamilton Depression Scale (HAMD), and the recurrence rate at follow-ups. Safety indices including the adverse events (AEs) and related laboratory tests were evaluated.ResultsPrimary outcome: IBS-SSS at baseline, weeks 2, 4, 6 showed no statistical significance in both full analysis set (FAS) and per protocol set (PPS, P>0.05). After 6 weeks of treatment, the total effective rate of IBS-SSS scores in the treatment group (147/171,86.0%) was higher than the control group (143/171, 83.6%) by FAS (P>0.05). In regard to secondary outcomes, after 6-week treatment, there was no significant difference in AR rate, total score of IBS-QOL, improvement of HAMD and HAMA total scores between the two groups (P>0.05). The recurrence rate at 8-week follow-up was 12.35% (10/18) in treatment group and 15.79% (12/76) in control group, respectively (P>0.05). A total of 21 AEs occurred in 15 cases, of which 11 occurred in 8 cases in the treatment group and 10 AEs in 7 cases in the control group. The incidence of AEs had no statistical significance between the two goups (P>0.05).ConclusionTongxiening Granules could relieve the symptoms of patients with IBS-D and the treatment effect was comparable to pinaverium bromide. (No. ChiCTR-IPR-15006415)

Background Irritable bowel syndrome (IBS) is a chronic gastrointestinal disorder characterized by abdominal pain and change of bowel habit without organic disease. A global perspective given by the World Gastroenterology Organization (WGO) points out that IBS can impact the quality of an individual’s daily life, cause socioeconomic problems and potentially impair the patient-physician relationship. It remains a problem to treat IBS due to the complicated pathophysiology. Acupuncture is an alternative therapy recommended for IBS. The aim of this study is to investigate the efficacy and safety of acupuncture therapy for patients with IBS. We also want to explore the correlation between IBS-gene subtypes and acupuncture effect. Methods/design A multicenter randomized controlled trial will be performed in seven hospitals. Six hundred participants will be stratified into two strata (IBS-C or IBS-D). Then, patients within each stratum will be divided into an experimental group and a control group randomly. The experimental group is treated with acupuncture while the control group is treated with Western medicine. All the patients will receive a 6-week treatment and a 3-month follow-up. The primary outcome is the IBS-Symptom Severity Score (IBS-SSS), the secondary outcome is the score of the IBS-Quality of Life (IBS-QoL).The correlation between IBS-gene subtypes and acupuncture effect will be detected based on polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Outcome measures (including primary and secondary outcome measures) are collected at baseline,1 week, 2 weeks, 4 weeks, and 6 weeks of the intervention, and 12 weeks after the intervention. Discussion This is a multicenter randomized controlled trial for IBS in China. It may clarify the efficacy of acupuncture as an alternative therapy for IBS. This is the first time ever that the potential mechanism of IBS based on genomics has been investigated. Trial registration Chinese Clinical Trials Register, ID: ChiCTR-IOR-15006259 . First registered on 14 April 2015.

Aim： （5R）-5-hydroxytriptolide （LLDT-8） displayed anti-arthritis and anti-allogenic transplantation rejection activities in our previous studies. Here, we aim to further clarify the effect of LLDT-8 on the pro-inflammatory cytokine IFN-γ. Methods： T cells were activated with anti-CD3 antibody or concanavalin A （ConA）. The expression of cell surface molecules was detected with flow cytometry. Cells were labeled with carboxyfluorescein diacetate succinimidyl ester （CFSE） to test cell division. IFN-γ production was determined by enzyme-linked immunosorbent assay. Cell proliferation was evaluated by [^3H]-thymidine uptake. Mice were immunized with ovalbumin to assess the in vivo immune response. RT-PCR and Real-time PCR were applied to determine the mRNA expression. The protein phosphorylation levels were detected by Western immunoblot assay. Results： LLDT- 8 at 100 nmol/L did not change the CD25, CD69, and CD154 expressions in anti- CD3-stimulated T cells. LLDT-8 markedly blocked the cell division of CD4 and CD8 T cells after ConA stimulation. LLDT-8 inhibited T cell-derived IFN-γ production. Moreover, LLDT-8 suppressed the ovalbumin-specific T cell proliferation and IFN-ygeneration. In anti-CD3-activated T cells, LLDT-8 abrogated the mRNA expression of signal transducer and activator of transcription 1 （STAT1）, T- box transcription factor, IL-12 receptor β2, STAT4, and interferon regulatory factor l in the IFN-γ expression pathway. Western blot analysis showed that LLDT- 8 blocked the phosphorylation levels of extracellular signal-regulated kinase, stress-activated protein kinase （SAPK）/c-Jun N-terminal kinase, and p38 mitogenactivated protein kinase in anti-CD3 plus anti-CD28-activated T cells. In addition, LLDT-8 reduced the transcripts of macrophage inflammatory protein （Mip）-1 α, Mip-1β, regulated upon activation normally T-cell expressed and secreted, inducible protein-10, IFN-inducible T cell a chemoattractant, and monokine induced by IFN-γ in IFN-γ-stimulated murine macrophage cell line Raw 264.7 cells. Conclusion： LLDT-8 was a potential inhibitor for IFN-γ-associated signaling.