Predicting mechanism of immune response in microsatellite instability colorectal cancer.

Colorectal cancer (CRC), also known as colon cancer, is the third most common cancer and the fourth most cause of cancer-related death in the world. CRC can be classified into two major subtypes, including microsatellite instability (MSI) and microsatellite stability (MSS), which showed different characteristics in immunotherapy. Low sensitivity of diagnostic biomarkers and metastasis are still the principal cause of mortality, especially in MSI. Here, applying computational programs, we identified recurring expression programs based on single cell RNA sequencing (scRNA-Seq) data of CRC cell lines. Notably, three MSI specific recurring modules were identified by non-negative matrix factorization (NMF). High NMF score genes enriched in the function of metabolism and inflammatory response. Focusing on top specific active transcription factor (TF), RUNX3 (Runt-related transcription factor 3), our results suggest that T cell infiltration was increased in RUNX3 high MSI CRC samples. Unbiased Gene Set Enrichment Analysis (GSEA) showed that RUNX3 was strongly associated with immune and metastasis related functions, such as Interferon Gamma (IFN-γ) and EPITHELIAL MESENCHYMAL TRANSITION (EMT). In addition, RUNX3 shows specific highly activated at epigenetic level in MSI compared with other gastrointestinal carcinomas. Positive correlation between RUNX3 and most immune checkpoints further confirmed RUNX3 might have crucial roles in MSI cancer progression and immunotherapy. Taken together, these results indicate significant tumor heterogeneity of two CRC subtypes at single-cell level and epigenetic modification level. These results also linked transcriptional dysregulation with immune infiltration at single-cell level in MSI, which may advance the application of scRNA-Seq technology in immunotherapy and contribute to developing novel biomarkers of this malignancy.

LINC00858 facilitates formation of hepatic metastases from colorectal cancer via regulating the miR-132-3p/IGF2BP1 axis.

Hepatic metastasis is a major cause of colorectal cancer (CRC)-related deaths. Presently, the role of long non-coding RNAs (lncRNAs) in hepatic metastases from CRC is elusive. We dissected possible interplay between LINC00858/miR-132-3p/IGF2BP1 via bioinformatics approaches. Subsequently we analyzed mRNA expression of LINC00858, miR-132-3p and IGF2BP1 through qRT-PCR. Western blot was used to detect protein expression of IGF2BP1. RNA immunoprecipitation chip and dual-luciferase assay validated interaction between LINC00858 and miR-132-3p, as well as miR-132-3p and IGF2BP1. Cell viability, invasion, and migration were examined via CCK-8, colony formation, transwell and wound healing assays. Effect of LINC00858 on CRC hepatic metastases was validated via in vivo assay. Upregulated LINC00858 and IGF2BP1, and downregulated miR-132-3p were predicted in tumor tissues of patients with hepatic metastases from CRC. There were targeting relationships between LINC00858 and miR-132-3p, as well as miR-132-3p and IGF2BP1. Besides, LINC00858 facilitated progression of CRC cells. Rescue assay suggested that silencing LINC00858 suppressed CRC cell progression, while further silencing miR-132-3p or overexpressing IGF2BP1 reversed such effects. LINC00858 could facilitate CRC tumor growth and hepatic metastases. LINC00858 induced CRC hepatic metastases via regulating miR-132-3p/ IGF2BP1, and this study may deliver a new diagnostic marker for the disease.

Prognostic Factors in Stage IV Colorectal Cancer Patients With Resection of Liver and/or Pulmonary Metastases: A Population-Based Cohort Study.

Importance: Currently, surgical resection of distant metastatic lesions has become the preferred treatment for select colorectal cancer (CRC) patients with liver metastasis (LM) and/or pulmonary metastasis (PM). Metastasectomy is the most common curative method. However, evidence of the factors affecting the prognosis of CRC patients after resection of LM and/or PM is still insufficient. Objective: To explore the prognostic factors of CRC patients with LM and/or PM who have undergone resection of metastatic tumors and to provide reliable selection factors for surgical treatment in patients affected by LM and/or PM from CRC. Methods: The SEER database was used to identify eligible CRC LM and/or PM patients who underwent resection of the primary tumor and distant metastases from January 1, 2010, to December 31, 2018. The Kaplan-Meier method was used to calculate survival, and comparisons were performed using the log-rank test for univariate analysis. A Cox proportional hazards regression model was used to identify prognostic factors for the multivariate analysis. The outcomes included overall survival (OS) and cancer-specific survival (CSS). Results: A total of 3,003 eligible colorectal cancer patients with LM and/or PM were included in this study. The 3-year and 5-year OS rates were 53% and 33.6%, respectively, and the 3-year and 5-year CSS rates were 54.2% and 35.3%, respectively. In the adjusted multivariate analysis, age < 65 years (OS: p=0.002, CSS: p=0.002) was associated with better long-term outcomes, and primary tumors located on the left side of the colon (OS: p=0.004, CSS: p=0.006) or rectum (OS: p=0.004, CSS: p=0.006), T3 stage (OS: p<0.001, CSS: p<0.001), number of regional lymph nodes examined ≥ 12 (OS: p<0.001, CSS: p=0.001), and CRC LM (OS: p<0.001, CSS: p<0.001) were positive prognostic factors for survival after resection of metastatic tumors. Conclusion: Age < 65 years is associated with better long-term outcomes in colorectal cancer patients with LM and/or PM, analogously to the left sided primary tumor, T3 stage, number of regional lymph nodes examined ≥ 12 and liver metastases.

Mini Percutaneous Nephrolithotomy Is a Noninferior Modality to Standard Percutaneous Nephrolithotomy for the Management of 20-40mm Renal Calculi: A Multicenter Randomized Controlled Trial.

BACKGROUND: High quality of evidence comparing mini percutaneous nephrolithotomy (mPNL) with standard percutaneous nephrolithotomy (sPNL) for the treatment of larger-sized renal stones is lacking. OBJECTIVE: To compare the efficacy and safety of mPNL and sPNL for the treatment of 20-40mm renal stones. DESIGN, SETTING, AND PARTICIPANTS: A parallel, open-label, and noninferior randomized controlled trial was performed at 20 Chinese centers (2016-2019). The inclusion criteria were patients 18-70 yr old, with normal renal function, and 20-40mm renal stones. INTERVENTION: Percutaneous nephrolithotomy PNL was performed using either 18 F or 24 F percutaneous nephrostomy tracts. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary outcome was the one-session stone-free rate (SFR). The secondary outcomes included operating time, visual analog pain scale (VAS) score, blood loss, complications as per the Clavien-Dindo grading system, and length of hospitalization. RESULTS AND LIMITATIONS: The 1980 intention-to-treat patients were randomized. The mPNL group achieved a noninferior one-session SFR to the sPNL group by the one-side noninferiority test (0.5% [difference], p <  0.001). The transfusion and embolization rates were comparable; however, the sPNL group had a higher hemoglobin drop (5.2 g/l, p <  0.001). The sPNL yielded shorter operating time (-2.2 min, p = 0.008) but a higher VAS score (0.8, p <  0.001). Patients in the sPNL group also had longer hospitalization (0.6 d, p <  0.001). There was no statistically significant difference in fever or urosepsis occurrences. The study's main limitation was that only 18F or 24F tract sizes were used. CONCLUSIONS: Mini mPNL achieves noninferior SFR outcomes to sPNL, but with reduced bleeding, less postoperative pain, and shorter hospitalization. PATIENT SUMMARY: We evaluated the surgical outcomes of percutaneous nephrolithotomy using two different sizes of nephrostomy tracts in a large population. We found that the smaller tract might be a sensible alternative for patients with 20-40mm renal stones.

Plasma-Liquid Interface Manipulated by Chamber Structure: An Experimental and Theoretical Approach.

To respond to global challenges of environmental contaminations, pursue more advanced material technologies, and achieve novel biomedical therapies, a variety of plasmas have been applied to wastewater and food processing, biomaterial treatments, and plasma-liquid ignitions. As these applications highly depend on the plasma-liquid interactions, researchers are now focusing on the physical and chemical reactions on the plasma-liquid interface. With massive publications reporting the molecular transfers, chemical pathways, and their effects on plasma treatments, this work provides a new point of view that the plasma-liquid interface can be manipulated by the chamber structure. In the experiment, plasma jet expansion in water is recorded in a cylinder chamber and a stepped-wall one. Data collected from the images show that the stepped-wall structure results in a shorter axial interface propagation, a small volume, more symmetry for the plasma jet, and more stability for the interface. To discover the physical mechanism behind these phenomena, we derived the momentum and energy equations for the plasma-liquid interface during its propagation. Those equations reveal how the stepped-wall structure can be used to manipulate the interface behaviors. Along with our experimental and theoretical investigation of the plasma-liquid interface, such information also sheds light on how the chamber wall structure can be used to manipulate the interface chemical reaction rates, stability, and expansion rate. This work is thus a basis of the future optimization for plasma-liquid treatments and ignitions which will be equipped with a flexible wall controlled by artificial intelligence to automatically achieve a variety of plasma treatment requirements.

The status and characteristics of urinary stone composition in China.

OBJECTIVES: To explore characteristics of urinary stone composition in China, and determine the effects of gender, age, body mass index (BMI), stone location, and geographical region on stone composition. PATIENTS AND METHODS: We prospectively used Fourier-transform infrared spectroscopy to analyse stones from consecutive patients presenting with new-onset urolithiasis at 46 hospitals in seven geographical areas of China, between 1 June 2010 and 31 May 2015. Chi-squared tests and logistic regression analyses were used to determine associations between stone composition and gender, age, BMI, stone location, and geographical region. RESULTS: The most common stone constituents were: calcium oxalate (CaOx; 65.9%), carbapatite (15.6%), urate (12.4%), struvite (2.7%), and brushite (1.7%). CaOx and urate stones occurred more frequently in males, whereas carbapatite and struvite were more common in females (P < 0.01). CaOx and carbapatite were more common in those aged 30-50 and 20-40 years than in other groups. Brushite and struvite were most common amongst those aged <20 and >70 years. The detection rate of urate increased with age, whilst cystine decreased with age. Obese patients were more likely to have urate stones than carbapatite or brushite stones (P < 0.01). CaOx, carbapatite, brushite, and cystine stones were more frequently found in the kidney than other types, whereas urate and struvite were more frequent in the bladder (P < 0.01). Stone composition varied by geographical region. CONCLUSIONS: The most common stone composition was CaOx, followed by carbapatite, urate, struvite, and brushite. Stone composition differed significantly in patients grouped by gender, age, BMI, stone location, and geographical region.

Integrated analysis of quantitative proteome and transcriptional profiles reveals abnormal gene expression and signal pathway in bladder cancer.

BACKGROUND: Bladder cancer (BCa) is a tumor associated with high morbidity and mortality and its incidence is increasing worldwide. However, the pathogenesis of bladder cancer is not well understood. OBJECTIVE: To further illustrate the molecular mechanisms involved in the pathogenesis of BCa and identify potential therapeutic targets, we combined the transcriptomic analysis with RNA sequencing and tandem mass tags (TMT)-based proteomic methods to quantitatively screen the differentially expressed genes and proteins between bladder cancer tissues (BC) and adjacent normal tissues (AN). RESULTS: Transcriptome and proteome studies indicated 7094 differentially expressed genes (DEGs) and 596 differentially expressed proteins (DEPs) between BC and AN, respectively. GO enrichment analyses revealed that cell adhesion, calcium ion transport, and regulation of ATPase activity were highly enriched in BCa. Moreover, several key signaling pathway were identified as of relevance to BCa, in particular the ECM-receptor interaction, cell adhesion molecules (CAMs), and PPAR signaling pathway. Interestingly, 367 genes were shared by DEGs and DEPs, and a significant positive correlation between mRNA and translation profiles was found. CONCLUSION: In summary, this joint analysis of transcript and protein profiles provides a comprehensive reference map of gene activity regarding the disease status of BCa.

Design and discovery of a novel half-Heusler transparent hole conductor made of all-metallic heavy elements.

Transparent conductors combine two generally contradictory physical properties, but there are numerous applications where both functionalities are crucial. Previous searches focused on doping wide-gap metal oxides. Focusing instead on the family of 18 valence electron ternary ABX compounds that consist of elements A, B and X in 1:1:1 stoichiometry, we search theoretically for electronic structures that simultaneously lead to optical transparency while accommodating intrinsic defect structures that produce uncompensated free holes. This leads to the prediction of a stable, never before synthesized TaIrGe compound made of all-metal heavy atom compound. Laboratory synthesis then found it to be stable in the predicted crystal structure and p-type transparent conductor with a strong optical absorption peak at 3.36 eV and remarkably high hole mobility of 2,730 cm(2) V(-1) s(-1) at room temperature. This methodology opens the way to future searches of transparent conductors in unexpected chemical groups.

Stereotactic localisation system: a modified puncture technique for percutaneous nephrolithotomy.

The objective of the study was to establish and evaluate a modified puncture and dilation technique-"stereotaxic localisation" system-and the corresponding instruments for percutaneous nephrostomy. Four hundred patients were randomised to the intervention group (200 cases, stereotaxic location puncture and dilation procedures) and the traditional group (200 cases, traditional procedure) under X-ray guidance. In the modified intervention system, the distance and horizontal angle of the puncture pathway between the puncture point and the target site were calculated accurately. The time for punctures, time with X-ray exposure and operation, success rate of each puncture to access the target, number of patients requiring blood transfusion, stone clearance, drops of haemoglobin and days of hospital stay were compared between the two groups. In the traditional and intervention groups, the time for puncture was 17 and 7 min, respectively; the X-ray exposure time was 9.1 and 1.3 min; the cases requiring blood transfusion were 9 and 5; and the success rates for each puncture to access the target were 42.9 and 88.0%, all with statistical difference (p < 0.01). The other outcomes and complications revealed similar trends. The stereotaxic localisation system for puncture is statistically better than the traditional procedure used in this study. The stereotaxic localisation system in this study is safer and more accurate, and provides easier access to the target with less bleeding and reduced exposure to X-ray compared to the traditional puncture and dilation procedures of percutaneous nephrostomy.

First-principles study on thermodynamic properties and phase transitions in TiS(2).

Structural and vibrational properties of TiS(2) with the CdI(2) structure have been studied to high pressures from density functional calculations with the local density approximation (LDA). The calculated axial compressibility of the CdI(2)-type phase agrees well with experimental data and is typical of layered transition-metal dichalcogenides. The obtained phonon dispersions show a good correspondence with available experiments. A phonon anomaly is revealed at 0 GPa, but is much reduced at 20 GPa. The thermodynamic properties of this phase were also calculated at high pressures and high temperatures using the quasi-harmonic approximation. Our LDA study on the pressure-induced phase transition sequence predicts that the CdI(2)-type TiS(2), the phase stable at ambient conditions, should transform to the cotunnite phase at 15.1 GPa, then to a tetragonal phase (I4/mmm) at 45.0 GPa. The tetragonal phase remains stable to at least 500 GPa. The existence of the tetragonal phase at high pressures is consistent with our previous findings in NiS(2) (Yu and Ross 2010 J. Phys.: Condens. Matter 22 235401). The cotunnite phase, although only stable in a narrow pressure range between 15.1 and 45.0 GPa, displays the formation of a compact S network between 100 and 200 GPa, which is evidenced by a kink in the variation of unit cell lengths with pressure. The electron density analysis in cotunnite shows that valence electrons are delocalized from Ti atoms and concentrated near the S network.

[Indwelling the anterior urethral stent: a good treatment option for anterior urethral stricture].

OBJECTIVE: To observe the clinical effect of indwelling the anterior urethral stent in the treatment of anterior urethral stricture. METHODS: We included 38 patients with anterior urethral stricture in the treatment group, and another 38 in the control, the former treated by indwelling the anterior urethral stent, and the latter by urethral dilatation. Then we analyzed the clinical results by comparing the Qmax, urinary hesitancy and numbers of urethral dilations between the two groups. RESULTS: Compared with the controls, the patients of the treatment group showed an obvious increase in Qmax, a significant decrease in the number of urethral dilatations, and a marked improvement of the quality of life. Six months after the stent removal, there were significantly more patients with Qmax > 15 ml/s in the treatment group than in the control (P < 0.05). CONCLUSION: Indwelling the anterior urethral stent is a desirable option for the treatment of anterior urethral stricture, which is simple, safe, effective and reliable, and can be applied to general clinical practice.

Prediction of high-pressure polymorphism in NiS2 at megabar pressures.

A sequence of pressure-induced phase transitions of vaesite, NiS(2), with pyrite structure, has been established from static LDA calculations. A dozen AX(2) candidate structures have been studied at high pressures including cotunnite (α-PbCl(2)), which is commonly observed in other AX(2) compounds at high pressures. At 150 GPa, vaesite transforms to a tetragonal phase (P4(2)/n) rather than cotunnite. This tetragonal structure is characterized by layers of Ni atoms in eight-fold coordination with S atoms rather than the nine-fold coordination observed in cotunnite. With further compression to about 7.5 Mbar, the tetragonal phase transforms into a hexagonal AlB(2)-type structure (P6/mmm) which is characterized by planar hexagonal layers of S intercalated by Ni atoms where each Ni atom is 12-fold coordinated by S atoms. Calculated band structures and valence electron density maps show S-S and Ni-S bonded interactions for NiS(2) under these extremely compressed conditions. The tetragonal phase may have geophysical implications if present in the Earth's core.