Alternative polyadenylation quantitative trait methylation mapping in human cancers provides clues into the molecular mechanisms of APA.

Genetic variants are involved in the orchestration of alternative polyadenylation (APA) events, while the role of DNA methylation in regulating APA remains unclear. We generated a comprehensive atlas of APA quantitative trait methylation sites (apaQTMs) across 21 different types of cancer (1,612 to 60,219 acting in cis and 4,448 to 142,349 in trans). Potential causal apaQTMs in non-cancer samples were also identified. Mechanistically, we observed a strong enrichment of cis-apaQTMs near polyadenylation sites (PASs) and both cis- and trans-apaQTMs in proximity to transcription factor (TF) binding regions. Through the integration of ChIP-signals and RNA-seq data from cell lines, we have identified several regulators of APA events, acting either directly or indirectly, implicating novel functions of some important genes, such as TCF7L2, which is known for its involvement in type 2 diabetes and cancers. Furthermore, we have identified a vast number of QTMs that share the same putative causal CpG sites with five different cancer types, underscoring the roles of QTMs, including apaQTMs, in the process of tumorigenesis. DNA methylation is extensively involved in the regulation of APA events in human cancers. In an attempt to elucidate the potential underlying molecular mechanisms of APA by DNA methylation, our study paves the way for subsequent experimental validations into the intricate biological functions of DNA methylation in APA regulation and the pathogenesis of human cancers. To present a comprehensive catalog of apaQTM patterns, we introduce the Pancan-apaQTM database, available at https://pancan-apaqtm-zju.shinyapps.io/pancanaQTM/.

Identification of potential functional variants and genes at 18q21.1 associated with the carcinogenesis of colorectal cancer.

Genome-wide association studies (GWAS) have identified more than 160 susceptibility loci for colorectal cancer (CRC). The effects of these variants, particularly their mechanisms, however, remain unclear. In this study, a comprehensive functional annotation of CRC-related GWAS signals was firstly conducted to identify the potential causal variants. We found that the SNP rs7229639 in intron 3 of SMAD7 at 18q21.1 might serve as a putative functional variant in CRC. The SNP rs7229639 is located in a region with evidence of regulatory potential. Dual-luciferase reporter assays revealed that three other SNPs (rs77544449, rs60385309 and rs72917785), in strong linkage disequilibrium (LD) with rs7229639, exhibited allele-specific enhancer activity, of which one of the target genes may conceivably be LIPG, as suggested by eQTL association data and Hi-C data. We also verified that LIPG promoted malignancy of CRC cells in vitro, with supporting clinical data indicating that LIPG is upregulated and correlated with a poor prognosis in CRC. Finally, pitavastatin was observed to exhibit an anti-CRC activity and modest inhibition of LIPG mRNA levels. Collectively, our data suggest that these functional variants at 18q21.1 are involved in the pathogenesis of CRC by modulating enhancer activity, and possibly LIPG expression, thus indicating a promising therapeutic target for CRC. The results of functional annotation in our investigation could also serve as an inventory for CRC susceptibility SNPs and offer guides for post-GWAS downstream functional studies.

[Rapid identification and differential markers of Curcumae Radix decoction pieces of different sources based on Heracles Neo ultra-fast gas phase electronic nose].

Since Curcumae Radix decoction pieces have multiple sources, it is difficult to distinguish depending on traditional cha-racters, and the mixed use of multi-source Curcumae Radix will affect its clinical efficacy. Heracles Neo ultra-fast gas phase electronic nose was used in this study to quickly identify and analyze the odor components of 40 batches of Curcumae Radix samples from Sichuan, Zhejiang, and Guangxi. Based on the odor fingerprints established for Curcumae Radix decoction pieces of multiple sources, the odor components was identified and analyzed, and the chromatographic peaks were processed and analyzed to establish a rapid identification method. Principal component analysis(PCA), discriminant factor analysis(DFA), and soft independent modeling cluster analysis(SIMCA) were constructed for verification. At the same time, one-way analysis of variance(ANOVA) combined with variable importance in projection(VIP) was employed to screen out the odor components with P<0.05 and VIP>1, and 13 odor components such as ß-caryophyllene and limonene were hypothesized as the odor differential markers of Curcumae Radix decoction pieces of diffe-rent sources. The results showed that Heracles Neo ultra-fast gas phase electronic nose can well analyze the odor characteristics and rapidly and accurately discriminate Curcumae Radix decoction pieces of different sources. It can be applied to the quality control(e.g., online detection) in the production of Curcumae Radix decoction pieces. This study provides a new method and idea for the rapid identification and quality control of Curcumae Radix decoction pieces.

Magnetoelectric Effect in Garnet Mn3Al2Ge3O12.

Searching for novel magnetoelectric (ME) materials has been one of the major issues of multiferroics. In this work, we present a systematic research study on garnet Mn3Al2Ge3O12, including structural, magnetic, heat capacity, and ME characterizations. Below the Néel temperature TN ∼ 6.8 K, Mn2+ spins form a long-range antiferromagnetic order, and a magnetic field H-driven electric polarization P is identified simultaneously. The relationship between P and H is nonlinear under low H and becomes linear under high H. Such transition is believed to originate from the H-induced variation of the magnetic structure. In addition, the P reaches 0.6 µC/m2 under µ0H = 9 T, corresponding to an ME coupling coefficient of αME ∼ 0.08 ps/m under high H. The small αME is attributed to the weak spin-orbit coupling and weak magnetic interactions in Mn3Al2Ge3O12. Furthermore, we realize the stable control of P by periodically varying H, which is crucial for potential application. We provide a rare case that a garnet material shows a first-order ME effect.

Spectrum-continuous narrowband filter with an enhanced flat-top passband and sharp roll-off performance.

We demonstrate a spectrum-continuous narrowband filter based on multi-section Mach-Zehnder interferometer (MZI) structures on a silicon nitride platform. Enhanced in-band flatness and sharp out-of-band roll-off features are achieved by cascading MZIs of specific functionalities in a series. This filter is fabricated in a single chip with a total waveguide length exceeding 237 cm. We experimentally demonstrate for the first time, to the best of our knowledge, a four-channel spectrum-continuous filter with a 3 dB bandwidth of 580 MHz, a 1 dB fluctuation bandwidth as high as 356 MHz, and an excellent 20 dB roll-off factor of 1.26 that are obtained simultaneously. Both the optical and electrical experimental results show that the proposed filter can play a key role in integrated microwave photonic front-end systems.

Protective effects of total flavonoids from Alpinia officinarum rhizoma against ethanol-induced gastric ulcer in vivo and in vitro.

CONTEXT: Alpinia officinarum Hance (Zingiberaceae) is traditionally used to treat inflammation, pain, colds and digestive diseases. OBJECTIVE: To investigate the potential protective mechanism of total flavonoids from the rhizomes of A. officinarum (F-AOH) in ethanol-induced acute gastric in vivo and in vitro. MATERIALS AND METHODS: In vivo: Gastric damage was induced in BALB/c mice by administering ethanol (10 mL/kg) after oral treatment with F-AOH at 126.8, 63.4 and 31.7 mg/kg or ranitidine (Ran) at 100 mg/kg (1 week of continuous gavage). In vitro: Gastric mucosal epithelial cells (GES-1) were incubated with F-AOH (8, 4 and 2 µg/mL) for 16 h and treated with 7% ethanol for 4 h. The extent of gastric damage was assessed histopathologically, and the expression of NF-κB, COX-2, TNF-α, iNOS and IL-1ß was quantified by Western blot analysis. In addition, proinflammatory mediators and concentrations of motilin (MTL) and gastrin (GAS) were measured by ELISA test. RESULTS: F-AOH effectively reduced the ulcer index (from 23.4 ± 4.28 to 8.32 ± 1.5) and reduced release of inflammatory mediators (IL-1ß, IL-6, TNF-α and PGE2), increased the content of nitric oxide and improved GAS and MTL secretion. The 50% inhibitory concentration (IC50) of F-AOH on cell damage was 17 µg/mL. F-AOH increased ethanol-induced cell survival (from 47 to 85%) and inhibited the expression of NF-κB, COX-2, TNF-α, IL-1ß and iNOS proteins. CONCLUSIONS: F-AOH inhibits ethanol-induced gastric mucosal damage, provides a theoretical basis for galangal in the treatment of other causes of GU, and promotes the application of galanga in the treatment of GU.

Development of propidium monoazide-recombinase polymerase amplification (PMA-RPA) assay for rapid detection of Streptococcus pyogenes and Streptococcus agalactiae.

Streptococcus pyogenes (Group A Streptococcus, GAS) and Streptococcus agalactiae (Group B Streptococcus, GBS) are common pathogens that threaten public health. In this study, a double recombinase polymerase (RPA) amplification assay was developed to rapidly detect these pathogens. Specificity tests revealed that the GAS and GBS strains were positive for speB and SIP genes, respectively. In clinical samples, the double assay performed similarly to the traditional biochemical method. The limits of detection were both ≤100 copies per reaction. In tests for simulant-contaminated samples, bacterial-culture media containing 103 CFU/mL original concentrations of S. pyogenes and S. agalactiae were positive in RPA assays after incubating for 4 h. Results can be obtained at 37 °C in 20 min. To determine whether propidium monoazide (PMA) can eliminate the influence of DNA extracted from dead cells, a bacterial suspension was treated with PMA before DNA extraction. Findings of RPA assay showed that DNA extracted from dead cells had no fluorescence signal. Therefore, the PMA-RPA assay is a promising technology for field tests and rapid point-of-care diagnosis.

Development and validation of an LC-MS/MS method for the determination of DPHB in rat plasma and its application in pharmacokinetic studies.

The aim of the present study was to develop a rapid, specific and sensitive LC-MS/MS method for the determination of DPHB [7-(4″-hydroxy-3″-methoxyphenyl)-1-phenyl-4-hepten-3-one] in rat plasma using yakuchinone A as an internal standard (IS). n-Hexane was used for the extraction of DPHB from rat plasma. Chromatographic separation of DPHB was achieved using a Kinetex XB-C18 column (2.10 × 50 mm, 2.6 µm) at 40°C. The mobile phase consisted of water (containing 0.1‰ formic acid, A) and acetonitrile (containing 0.1‰ formic acid, B) under a gradient elution at a flow rate of 0.3 mL min-1 . Positive electrospray ionization and multiple reaction monitoring mode were used for detection. The selected precursor ion to product ion pairs, m/z 311.3 → 137.0 for DPHB and m/z 313.1 → 137.0 for yakuchinone A, were monitored. Good linearity was observed over the concentration range from 2 to 2000 ng mL-1 (r = 0.9969). The recovery efficiency of DPHB from rat plasma was 54.8-69.7%, while the matrix effect ranged from 99.7 to 113%. Intra- and inter-day precision and accuracy values were within ±15% at three different quality control concentration levels. This validated method was successfully applied to pharmacokinetic studies in rats after a single p.o. or i.v. dose of DPHB solution. The route of administration significantly influenced systemic exposure to DPHB, and low bioavailability of DPHB was observed. The method developed here will be further improved and used in future pharmacokinetic studies.

Effects and possible mechanisms of Alpinia officinarum ethanol extract on indomethacin-induced gastric injury in rats.

CONTEXT: Alpinia officinarum Hance (Zingiberoside) has a long history in treating gastrointestinal diseases, but its mechanisms of action are not yet known. OBJECTIVE: To investigate the effects and underlying mechanisms of the ethanol extract of A. officinarum rhizomes in an indomethacin-induced gastric injury rat model. MATERIAL AND METHODS: Indomethacin (0.3 g/kg) was orally administered to Sprague-Dawley rats to induce gastric damage; after 7 h, the rats were treated with 0.03, 0.09, or 0.18 g/kg of the plant extract, galangin (0.2 g/kg), or bismuth potassium citrate (0.08 g/kg), once a day for 6 days. Rats in the control group received an equivalent volume of vehicle solution for 6 days. Gastric damage was evaluated by gross ulcer and histological indexes. Cyclooxygenase and non-cyclooxygenase pathway proteins were quantified by western blotting and ELISA. RESULTS: Alpinia officinarum extract ameliorated gastric injury in a dose-dependent manner, and 0.18 g/kg dose exhibited the best performance by reducing the gross ulcer (from 20.23 ± 1.38 to 1.66 ± 0.37) and histological (from 4.67 ± 1.03 to 0.33 ± 0.51) indexes, decreasing serum TNF-α level (14.17%), increasing serum VEGF level (1.58 times), increasing cyclooxygenase-1 level (1.25 times, p < 0.001) in the gastric mucosa, and reversing indomethacin-induced changes in the expression of non-cyclooxygenase pathway proteins (p < 0.05). Galangin was less effective as an antiulcer agent than the whole extract, indicating that other components also contributed to the protective effect. CONCLUSIONS: Alpinia officinarum extract and galangin exert antiulcer effects through cyclooxygenase and non-cyclooxygenase pathways validating use of galangin as a treatment for gastric damage.

Self-made cryopreservative fibrin glue applied in pterygium surgery: a novel practical technique.

PURPOSE: To introduce a novel practical technique of self-made cryopreservative fibrin glue (SMC) applied in pterygium surgery and to assess its safety and efficacy. METHODS: Forty-eight eyes of 48 patients with nasal primary pterygium were enrolled. The patients were equally assigned to 6 groups. Self-made fibrin glue was subpackaged and, respectively, cryopreserved for 3, 7, 15 days and 1, 2 and 3 months. At each time point, the asepsis of SMC was confirmed by bacterial culture and colony counting. In each group, corresponding SMC was applied to fix the autograft after the pterygium was removed (e.g., SMC 3d for group 1 and SMC 3m for group 6). All the patients were followed up postoperatively on days 1, 3, 7 and 14 and then at months 1, 3, 6. The main outcome measures included fixation success rate within two tries, postoperative discomfort, recurrence rate and complications. RESULTS: No colony growth was observed in all the fibrinogen and thrombin tubes sent. Five patients needed a second try with respective SMC during the autograft fixation, and there were no significant differences in SMC use times among the groups (P = 0.885). There were no significant differences in postoperative discomfort (day 1, 3, 7; P = 0.651, P = 0.269, P = 0.180, respectively) among the groups. By the end of 6-m follow-up, no infections and severe complications were observed in any group. The total recurrence rate was 3/48 (6%), and there were no significant differences in recurrences among the groups (P = 1.000). CONCLUSION: SMC is safe and effective for autograft fixation in pterygium surgery. This new practical technique will benefit the patients and surgeons in developing and underdeveloped country.

Use of chalazion clamp for excision of the eyelid margin lesion.

PURPOSE: Reconstruction after eyelid lesion excision is very important. It calls for preserving normal eyelid function for the protection of the eye and restoring good cosmesis. It is important to precisely align the tarsal plate. However, the unique anatomy of eyelids often makes haemostasis difficult and surgical field obscured. We report an effective method to solve this problem. METHOD: This retrospective study included 25 patients who underwent eyelid margin lesion excision using the chalazion clamp between March 2020 and October 2021. The chalazion clamp is placed on the desired location and tightened, providing a bloodless field for eyelid lesion removal. Without bleeding, visibility of the cut edges is improved considerably. It facilitates anatomical anastomosis of the tarsal plate. RESULTS: All 25 patients maintained normal eyelid function and good cosmesis, with no recurrence during the follow-up period. CONCLUSION: The use of the chalazion clamp during excision of the eyelid margin lesion could stabilize the eyelid, protect the eyeball from accidental injury and, and provide a clear bloodless operative field. It can ensure the neatness of the cut edges and offer better incision alignment for suture. It also avoids wasting too much time on haemostasis, without additional expensive equipment.

Climate change dominates the interannual variation of carbon export efficiency in each season in the Northern Gulf of Mexico during 1998-2011.

Carbon export efficiency is a key indicator of the capacity of biological pump, but the controlling mechanism of the efficiency remains unclear. Our findings revealed that interannual variations in seasonal carbon export efficiency are determined by direct factors including riverine nutrient fluxes, stratification, residence time. These direct factors are finally attributed to two indirect factors (human activities and climate change). We quantified the absolute contributions of direct and indirect factors to carbon export efficiency. The results showed that the carbon export efficiency in the northern Gulf of Mexico in spring (summer; autumn; winter) was driven by human activities, which accounted for an absolute contribution of 16.02% (7.20%; 4.00%; 8.49%, respectively) through riverine nutrient fluxes, and by climate change, which accounted for an absolute contribution of 33.51% (21.43%; 25.73%; 15.80%, respectively) through stratification and water residence time. Moreover, carbon export efficiency could be predicted by MEI of 8 months earlier.

Treatment of acute dacryocystitis by translacrimal canalicular drainage and D-silicone intubation.

AIM: To demonstrate the outcomes of translacrimal canalicular drainage using a lacrimal probe and intranasal drainage by D-silicone intubation for acute dacryocystitis (AD). METHODS: This retrospective study included 23 patients with AD and had undergone abscess decompression with the use of lacrimal probe and intranasal drainage by D-silicone intubation between January 2019 and December 2022. Patients received abscess decompression and systemic antibiotic-corticosteroid from the time of diagnosis. D-silicone tube was inserted within 10d after diagnosis and removed 3-6mo after intubation. The procedure and outcomes of this method were evaluated. RESULTS: All patients showed improvement of signs and symptoms of AD within 72h. No intraoperative and postoperative complications were observed. No recurrence of lacrimal sac abscesses occurred after D-silicone tube removed. CONCLUSION: Lacrimal probe and D-silicone intubation appear to be a feasible, minimally invasive, safe, and effective method, which could be a reasonable choice in the treatment of AD.

A review of typical biological activities of glycyrrhetinic acid and its derivatives.

Glycyrrhetinic acid, a triterpenoid compound primarily sourced from licorice root, exhibits noteworthy biological attributes, including anti-inflammatory, anti-tumor, antibacterial, antiviral, and antioxidant effects. Despite these commendable effects, its further advancement and application, especially in clinical use, have been hindered by its limited druggability, including challenges such as low solubility and bioavailability. To enhance its biological activity and pharmaceutical efficacy, numerous research studies focus on the structural modification, associated biological activity data, and underlying mechanisms of glycyrrhetinic acid and its derivatives. This review endeavors to systematically compile and organize glycyrrhetinic acid derivatives that have demonstrated outstanding biological activities over the preceding decade, delineating their molecular structures, biological effects, underlying mechanisms, and future prospects for assisting researchers in finding and designing novel glycyrrhetinic acid derivatives, foster the exploration of structure-activity relationships, and aid in the screening of potential candidate compounds.

Myotis bat STING attenuates aging-related inflammation in female mice.

Bats, notable as the only flying mammals, serve as natural reservoir hosts for various highly pathogenic viruses in humans (e.g., SARS-CoV and Ebola virus). Furthermore, bats exhibit an unparalleled longevity among mammals relative to their size, particularly the Myotis bats, which can live up to 40 years. However, the mechanisms underlying these distinctive traits remain incompletely understood. In our prior research, we demonstrated that bats exhibit dampened STING-interferon activation, potentially conferring upon them the capacity to mitigate virus- or aging-induced inflammation. To substantiate this hypothesis, we established the first in vivo bat-mouse model for aging studies by integrating Myotis davidii bat STING ( MdSTING) into the mouse genome. We monitored the genotypes of these mice and performed a longitudinal comparative transcriptomic analysis on MdSTING and wild-type mice over a 3-year aging process. Blood transcriptomic analysis indicated a reduction in aging-related inflammation in female MdSTING mice, as evidenced by significantly lower levels of pro-inflammatory cytokines and chemokines, immunopathology, and neutrophil recruitment in aged female MdSTING mice compared to aged wild-type mice in vivo. These results indicated that MdSTING knock-in attenuates the aging-related inflammatory response and may also improve the healthspan in mice in a sex-dependent manner. Although the underlying mechanism awaits further study, this research has critical implications for bat longevity research, potentially contributing to our comprehension of healthy aging in humans.

Analysis of endoscopic and pathological features of 6961 cases of gastric cancer.

Gastric cancer (GC) stage and tissue differentiation affect treatment efficacy and prognosis, highlighting the importance of understanding the risk factors that affect these parameters. Therefore, this study analyzed risk factors affecting the GC stage and differentiation and the relationships between the cancer site and the sex and age of the patient. We collected clinical data from 6961 patients with GC, including sex, age, endoscopic lesion location, and pathological differentiation. Patients were grouped based on GC stage (early or advanced), differentiation (well or poorly differentiated), and lesion site (upper stomach [cardia and fundus], middle stomach [gastric body], and lower stomach [gastric antrum]). Differences in sex, age, location, stage, and degree of differentiation were assessed based on these groupings. Univariate analysis revealed that the disease location and differentiation significantly differed based on the GC stage (P < 0.05), whereas sex, age, site, and stage significantly differed based on GC differentiation (P < 0.05). A multivariate analysis confirmed these factors as independent risk factors affecting GC. Moreover, lesion sites significantly differed between sexes (P < 0.05) and among age groups (P < 0.05). Although the effects of family history, lifestyle, and Helicobacter pylori infection status of the patients were not considered, this single-center retrospective study established independent risk factors for GC.Trial registration ChiCTR2200061989.

Research on the effects of processing Heishunpian from Aconiti lateralis radix praeparata on components and efficacy using the "step knockout" strategy.

Heishunpian is obtained through complex processing of Aconiti lateralis radix praeparata. However, the impact of each processing step on chemical compositions and pharmacological activities is still unclear. The mechanism of the processing needs to be further studied. The samples were all prepared using the "step knockout" strategy for UPLC-QTOF-MS analysis, and analgesic and anti-inflammatory efficacy evaluation. Each sample was analyzed by UPLC-QTOF-MS to determine the component differences. The hot plate test and acetic acid writhing test were used to evaluate the analgesic effect. Anti-inflammatory efficacy was evaluated by xylene-induced ear edema test. The correlation between components and efficacies was studied to screen the effective components for further investigating the processing of Heishunpian. Mass spectrum analysis results showed that 49 components were identified, and it appeared that brine immersion and rinsing had a great influence on the components. In the hot plate test, ibuprofen and Heishunpian had the most significant effect, while ibuprofen and the sample without rinsing showed the best efficacy for the acetic acid writhing test. The sample without dyeing had the best effect on ear edema. The correlation analysis indicated that mesaconine, aconine, 3-deoxyaconine, delbruine, and asperglaucide were potentially considered effective analgesic components. It is not recommended to remove brine immersion and rinsing. Boiling and steaming are necessary processes that improve efficacy. Dyeing, which does not have a significant impact on components and efficacy, may be an unnecessary process. This research has been of great significance in identifying anti-inflammatory and analgesic components and optimizing processing for Heishunpian.

[Study of the visual deficits pattern in strabismic and anisometropic amblyopia].

OBJECTIVE: To elucidate the difference in the pathogenesis between strabismic and anisometropic amblyopia. METHODS: It was a case-control study.We used psychophysical methods, including grating acuity, edge contrast sensitivity, contrast sensitivity function tests, and examined the visual functions of 150 cases from 8 to 40-year-old. Then we applied the Origin 8.0 software for statistical analysis of experimental data, we did the correlation analysis between the grating acuity, edge contrast sensitivity and optotype acuity, and the similarity comparison of the contrast sensitivity function curve between the strabismic and anisometropic amblyopia. RESULTS: The grating acuity had a strong correlation with optotype acuity, the correlation value was 0.81. The grating acuity of the strabismic group was roughly 15% lower than the whole abnormal population, for any given level of optotype acuity; the edge contrast threshold had a weak correlation with optotype acuity, the correlation value was 0.24. Anisometropia, for a given level of optotype acuity, had edge contrast thresholds that were 15% higher (worse) than the whole population, while strabismic and strabismic-anisometropia had edge contrast thresholds that are 17% lower (better) than the whole population. The CSF of all amblyopic eyes were reduced in comparison with the non-amblyopic eye of the same person, the peak sensitivity shifted toward to the low spatial frequency region, the CS curve was depressed especially in the middle and high spatial frequencies, there were no significant difference, but at low frequency area(1.0 c/d) there were statistically significant between the two types of amblyopia(t = 2.239, P < 0.05). CONCLUSION: There were differences in the patterns of visual loss between strabismic and anisometropic amblyopic patients.

Prognostic significance of high NPC2 expression in gastric cancer.

Gastric cancer is one of the most common malignancies worldwide, and the third leading cause of cancer-related death. The identification of novel biomarkers and therapeutic targets is critical to improve the prognosis. A total of 380 patients with primary gastric cancer from the TCGA database were analyzed. The receiver operating characteristic curves were plotted. We further evaluated the independent prognostic ability of NPC2 expression for overall survival (OS) and relapse-free survival (RFS) through the Kaplan-Meier curve and Cox analysis. The NPC2 expression was significantly higher (P < 0.001) in gastric cancer. High NPC2 expression was significantly (P < 0.0001) associated with poor OS and poor RFS. The age, stage, radiation therapy, residual tumor, and NPC2 expression showed independent prognostic value for OS. The gender and NPC2 expression showed independent prognostic value for RFS. The higher NPC2 expression was observed in gastric cancer, compared with adjacent normal tissue (P < 0.001), confirmed by the IHC staining. The CCK-8 assay showed that NPC2 knockdown inhibits cell proliferation while NPC2 overexpression promotes cell proliferation (P < 0.05). NPC2 expression may serve as a promising prognostic biomarker for patients with gastric cancer.

SCGN and STAT3 expressions are associated with the prognosis of ccRCC.

Clear cell renal cell carcinoma (ccRCC) is highly heterogeneous and accounts for about 70% of RCC. Its prognosis is worse than that of most histological types of RCC. In order to find potential biomarkers that may influence the prognosis and survival in ccRCC patients, we explored the expressions of STAT3, PDL1 and SCGN (secretagogin) in ccRCC based on the data of TCGA (n = 529), EMATAB-1980 (n = 99) and our own cohort (n = 99). Our study demonstrated that ccRCC patients with low STAT3 expression and high SCGN expression might have a better prognosis. No significant difference in the positive rate of SCGN expression was found when comparing the primary lesion with the matched metastatic liver lesions. The percentage of high SCGN expression in the primary lesion of metastatic ccRCC patients was significantly lower than that of patients with only the renal lesion. In view of the conclusion that STAT3 high expression cases are resistant to sunitinib, STAT3 immunohistochemistry results are essential for designing non-operative treatments. SCGN has the potential to become an indicator for subtype classification of ccRCC.