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Background: This study aimed to investigate the risk factors for complication of intra-abdominal infection (IAI) after endoscopic full-thickness resection of gastric submucosal tumors (GSMT) and to establish a nomogram prediction model for the occurrence of IAI. Methods: Clinical data of patients with GSMT who underwent endoscopic full-thick resection (EFR) from January 2018 to July 2023 were retrospectively analyzed. The patients were divided into IAI and non-IAI groups according to whether IAI occurred during postoperative hospitalization. Univariate and multivariate logistic regression analyses were performed on the relevant clinical data of patients in the two groups to screen the independent influencing factors for the occurrence of IAI. The nomogram model was constructed based on the independent influencing factors. Model discrimination was assessed by the area under the curve (AUC) of the receiver operating characteristic (ROC) curve. The consistency of model-predicted risk with actual risk was evaluated using the Hosmer-Lemeshow goodness-of-fit test. The clinical performance of the nomogram model was evaluated using decision curve analysis. Results: A total of 240 GSMT patients who underwent EFR procedures were finally included in this study, including 14 patients (5.83 %) in the IAI group and 226 patients in the non-IAI group. Univariate and multivariate logistic regression analyses showed that age (OR = 1.283, 95 % CI = 1.029–1.600), preoperative albumin (OR = 0.575, 95 % CI = 0.395–0.837), duration of operation (OR = 1.222, 95 % CI = 1.060–1.409), and hospitalization time (OR = 4.089, 95 % CI = 1.190–14.043) were independent influencing factors for the incidence of IAI in GSMT patients undergoing EFR surgery (P

Abstract Background In critically ill patients receiving invasive mechanical ventilation (IMV), it is unable to determine early which patients require tracheotomy and whether early tracheotomy is beneficial. Methods Clinical data of patients who were first admitted to the ICU and underwent invasive ventilation for more than 24 h in the Medical Information Marketplace in Intensive Care (MIMIC)-IV database were retrospectively collected. Patients were categorized into successful extubation and tracheotomy groups according to whether they were subsequently successfully extubated or underwent tracheotomy. The patients were randomly divided into model training set and validation set in a ratio of 7:3. Constructing predictive models and evaluating and validating the models. The tracheotomized patients were divided into the early tracheotomy group ( 7 days), and the prognosis of the two groups was analyzed. Results A total of 7 key variables were screened: Glasgow coma scale (GCS) score, pneumonia, traumatic intracerebral hemorrhage, hemorrhagic stroke, left and right pupil responses to light, and parenteral nutrition. The area under the receiver operator characteristic (ROC) curve of the prediction model constructed through these seven variables was 0.897 (95% CI: 0.876–0.919), and 0.896 (95% CI: 0.866–0.926) for the training and validation sets, respectively. Patients in the early tracheotomy group had a shorter length of hospital stay, IMV duration, and sedation duration compared to the late tracheotomy group (p

Abstract Fluoropyrimidine-based combination chemotherapy plus targeted therapy is the standard initial treatment for unresectable metastatic colorectal cancer (mCRC), but the prognosis remains poor. This phase 3 trial (ClinicalTrials.gov: NCT03950154) assessed the efficacy and adverse events (AEs) of the combination of PD-1 blockade-activated DC-CIK (PD1-T) cells with XELOX plus bevacizumab as a first-line therapy in patients with mCRC. A total of 202 participants were enrolled and randomly assigned in a 1:1 ratio to receive either first-line XELOX plus bevacizumab (the control group, n = 102) or the same regimen plus autologous PD1-T cell immunotherapy (the immunotherapy group, n = 100) every 21 days for up to 6 cycles, followed by maintenance treatment with capecitabine and bevacizumab. The main endpoint of the trial was progression-free survival (PFS). The median follow-up was 19.5 months. Median PFS was 14.8 months (95% CI, 11.6–18.0) for the immunotherapy group compared with 9.9 months (8.0–11.8) for the control group (hazard ratio [HR], 0.60 [95% CI, 0.40–0.88]; p = 0.009). Median overall survival (OS) was not reached for the immunotherapy group and 25.6 months (95% CI, 18.3–32.8) for the control group (HR, 0.57 [95% CI, 0.33–0.98]; p = 0.043). Grade 3 or higher AEs occurred in 20.0% of patients in the immunotherapy group and 23.5% in the control groups, with no toxicity-associated deaths reported. The addition of PD1-T cells to first-line XELOX plus bevacizumab demonstrates significant clinical improvement of PFS and OS with well tolerability in patients with previously untreated mCRC.

Tea is one of the most popular non-alcoholic beverages in the world, and free amino acids, especially theanine, make a major contribution to the umami taste of tea. However, the genetic basis of the variation in amino acid content in tea plants remains largely unknown. Here, we measured the free amino acid content in fresh leaves of 174 tea accessions over two years using a targeted metabolomics approach and obtained genotype data via RNA sequencing. Genome-wide association studies were conducted to investigate loci affecting the content of free amino acids. A total of 69 quantitative trait loci (–log10(P-value)>5) were identified. Functional annotation revealed that branched-chain amino acid aminotransferase, glutamine synthetase, nitrate transporter, and glutamate decarboxylase might be important for amino acid metabolism. Two significant loci, glutamine synthetase (Glu1, P=3.71×10−4; Arg1, P=4.61×10−5) and branched-chain amino acid aminotransferase (Val1, P=4.67×10−5; I_Leu1, P=3.56×10−6), were identified, respectively. Based on the genotyping result, two alleles of CsGS (CsGS-L and CsGS-H) and CsBCAT (CsBCAT-L and CsBCAT-H) were selected to perform function verification. Overexpression of CsGS-L and CsGS-H enhanced the contents of glutamate and arginine in transgenic plants, and overexpression of CsBCAT-L and CsBCAT-H promoted the accumulation of valine, isoleucine and leucine. Enzyme activity assay uncovered that SNP1054 is important for CsGS catalyzing glutamate into glutamine. Furthermore, CsGS-L and CsGS-H differentially regulated the accumulation of glutamine, and CsBCAT-L and CsBCAT-H differentially regulated the accumulation of branched-chain amino acids. In summary, the findings in our study would provide new insights into the genetic basis of amino acids contents variation in tea plants and facilitate the identification of elite genes to enhance amino acids content.

Our previous study reported that the metabolite of Bacillus subtilis BS-Z15 n-butanol site could reduce body weight gain in mice, showing anti-obesity effects. This study further demonstrated the effects of purified mycosubtilin on the body weight gain and gut microbiota of Kunming mice. 30 male Kunming white mice were randomly selected into three groups at four weeks of age: Control (group A), gavage-administered with saline daily; n-butanol site treated (group B), gavage-administered with n-butanol site metabolites (90 mg/kg); and mycosubtilin treated (group C), gavage-administered with mycosubtilin (6 mg/kg). Different groups’ gut microbiota compositions were analyzed using high-throughput sequencing technology. The results showed that the effects of mycosubtilin and n-butanol sites were consistent; the treatment groups showed a significant reduction in body weight gain as well as triglyceride and low-density lipoprotein contents as compared to the control group (P

Abstract Background Previous studies have shown that secondary metabolites of Bacillus subtilis strain Z15 (BS-Z15) are effective in treating fungal infections in mice. To evaluate whether it also modulates immune function in mice to exert antifungal effects, we investigated the effect of BS-Z15 secondary metabolites on both the innate and adaptive immune functions of mice, and explored its molecular mechanism through blood transcriptome analysis. Results The study showed that BS-Z15 secondary metabolites increased the number of monocytes and platelets in the blood, improved natural killer (NK) cell activity and phagocytosis of monocytes-macrophages, increased the conversion rate of lymphocytes in the spleen, the number of T lymphocytes and the antibody production capacity of mice, and increased the levels of Interferon gamma (IFN-γ), Interleukin-6 (IL-6), Immunoglobulin G (IgG) and Immunoglobulin M (IgM) in plasma. The blood transcriptome analysis revealed 608 differentially expressed genes following treatment with BS-Z15 secondary metabolites, all of which were significantly enriched in the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) terms for immune-related entries and pathways such as Tumor Necrosis Factor (TNF) and Toll-like receptor (TLR) signaling pathways, and upregulated expression levels of immune-related genes such as Complement 1q B chain (C1qb), Complement 4B (C4b), Tetracyclin Resistant (TCR) and Regulatory Factor X, 5 (RFX5). Conclusions BS-Z15 secondary metabolites were shown to enhance innate and adaptive immune function in mice, laying a theoretical foundation for its development and application in the field of immunity.

AIM: To investigate the short-term visual quality outcomes after femtosecond laser small incision lenticule extraction(SMILE)and evolution implantable collamer lens(EVO-ICL)implantation for the correction of moderate myopia.METHODS: Prospective control study. A total of 51 cases(51 eyes)with moderate myopia who underwent SMILE or EVO-ICL implantation surgery at Weifang Eye Hospital from April 2021 to February 2022 were selected. They were divided into SMILE group(30 patients, 30 eyes)and EVO-ICL group(21 patients, 21 eyes)according to the surgical methods. The changes of visual acuity [uncorrected distance visual acuity(UDVA), corrected distance visual acuity(CDVA)], diopter [spherical equivalent(SE)] and related parameters of optical quality analysis system(OQAS Ⅱ)were observed before surgery and at 1wk, 1 and 3mo after surgery, and the quality of vision(QoV)questionnaire was completed.RESULTS: At 3mo after surgery, the safety index(postoperative CDVA/preoperative CDVA)of SMILE gruop and EVO-ICL group were 1.20(1.00, 1.20)and 1.20(1.00, 1.38), respectively, the efficacy index(postoperative UDVA/preoperative CDVA)were 1.00(1.00, 1.20)and 1.00(1.00, 1.20), respectively, and the percentage of SE within ±0.50D was 87% and 100%, respectively. In SMILE group, the objective scattering index(OSI)was increased after surgery, while modulation transfer function cutoff frequency(MTF cutoff), contrast visual acuity(VA)100%, and VA20% at 1wk and 1mo after surgery, and Strehl ratio(SR)and VA9% at each time point after surgery were all decreased compared with those before surgery(all P0.05). The most common visual symptoms after SMILE and EVO-ICL implantation were visual haze and halos, respectively.CONCLUSION: Both SMILE and EVO-ICL implantation have good safety, efficacy and predictability in the short term after the correction of moderate myopia. Both groups had visual symptoms after surgery, but the overall satisfaction of patients was high. Furthermore, EVO-ICL implantation has better objective visual quality performance.

AIM:To observe the changes in corneal aberrations and the characteristics of visual quality after transepithelial photorefractive keratectomy(T-PRK)and femtosecond small incision lenticule extraction(SMILE)in the correction of low myopia.METHODS: Prospective cohort study. A total of 32 cases(32 eyes)with low myopia who underwent T-PRK surgery and 45 cases(45 eyes)of SMILE surgery at Weifang Eye Hospital from April 2021 to April 2022 were selected. The uncorrected visual acuity(UCVA), best corrected visual acuity(BCVA), spherical equivalent(SE), corneal higher-order aberrations(HOAs)and objective visual quality were compared between the two groups.RESULTS:All patients completed the surgery successfully without complications such as infection. At 3mo postoperatively, the safety index was 1.13±0.16 and 1.16±0.17(P=0.48)and the efficacy index was 1.10±0.20 and 1.15±0.18(P=0.27)in the T-PRK and SMILE groups, respectively. The percentage of UCVA(LogMAR)≤0 in the T-PRK and SMILE groups was 94% and 98%, respectively. The percentage of the residual SE within ±0.5D was 88% and 87% in the two groups, respectively. The HOAs and spherical aberration in both groups were significantly increased(P≤0.01), and the increase was not statistically significant between the two groups(P=0.31, 0.89). There was no significant change in horizontal coma, horizontal trefoil and vertical trefoil in both groups(P>0.05). The vertical coma in SMILE group was significantly increased(P0.05), and the increase was significantly greater in SMILE group than in T-PRK group(P0.05).CONCLUSION:Both T-PRK and SMILE showed good safety, efficacy, and visual quality in correcting low myopia, while SMILE induced more vertical coma than T-PRK.

AIM: To investigate the histological characteristics and ultrastructure of recurrent Chinese R124L mutated corneal dystrophy after keratoplasty. METHODS: The subjects were enrolled from a Chinese family of corneal dystrophy with R124L heterozygous gene mutation and with a history of consanguineous marriage. Normal corneal samples were used as controls. RESULTS: In this family, 2 patients (3 eyes) underwent penetrating keratoplasty (PKP) and 2 patients (4 eyes) underwent lamellar keratoplasty (LKP). They had recurrence at 33.5±3.0 (range 30-36)mo after keratoplasty. Among them, 1 patient (1 eye) underwent PKP again and 1 patient (2 eyes) underwent LKP again. In the R124L mutated recurrent corneal dystrophy, the corneal turbidity was mainly distributed from the upper corneal cortex to the anterior stroma; the corneal epithelium surface was rougher and more uneven; and, the corneal erosions were larger. Hematoxylin-eosin staining showed that the thickness of the corneal epithelium was uneven; the arrangement of the epithelial cells was disordered; and, some corneal epithelial cells were swollen. The results of Congo red staining, Masson's trichrome staining and Periodic acid-Schiff staining were positive, while that of Alcian blue staining was negative. Under a transmission electron microscope, deposition of high electron density substances between epithelial and basal cells, and, apoptosis of basal cells were observed. Many high electron density depositions were observed in the sub-epithelial and anterior corneal matrix. CONCLUSION: In the Chinese family of recurrent corneal dystrophy with R124L gene mutation, the corneal epithelia of the recurrent cases are rougher, and the corneal depositions are extracellular amyloid fibrin.

The soil’s rhizosphere is a highly active place where the exchange of substances and information occurs among plants, soils, and microorganisms. The microorganisms involved are crucial to the activities of plant growth and development, metabolism, and reproduction. Fritillaria L. medicinal plants are unique Chinese medicinal ingredients, but the continuous cropping obstacles formed in the artificial planting process is severely harmful to the growth and development of these medicinal plants. In this review, we summarized the current species and distribution of Fritillaria L. in China, and analyzed the changes in microbial diversity (mainly among bacteria and fungi) in the rhizosphere of these plants under long-term continuous cropping. The fungi showed an increasing trend in the soil rhizosphere, resulting in the transition of the soil from the high-fertility “bacterial type” to the low-fertility “fungal type” as planting years increased. Furthermore, the interaction between Fritillaria L. medicinal plants and the rhizosphere microorganisms was reviewed, and promising applications for the rhizosphere microbiome in the cultivation of Fritillaria L. medicinal plants were suggested. It is expected that this review will facilitate the in-depth understanding of rhizosphere microorganisms in the growth, accumulation of active ingredients, and disease control of Fritillaria L.

ObjectiveTo investigate the prevalence and influencing factors of osteoporosis among adults in Hebei province and to provide references for developing targeted osteoporosis prevention measures.MethodsA questionnaire survey and quantitative ultrasound bone density detection were conducted among 6195 permanent residents aged 20 – 80 years selected with multistage stratified cluster sampling in 7 districts or counties in Shijiazhuang, Chengde and Baoding city of Hebei province from July to September in 2017.ResultsAmong the participants, totally 89 osteoporosis cases were identified and the prevalence rate was 1.44%. Unconditional multivariate logistic regression analysis revealed that female gender and at older age were risk factors for osteoporosis; while, with an education of high school and above was a protective factor against osteoporosis.ConclusionThe prevalence of osteoporosis is relatively low and mainly influenced by gender, age and education level among adult residents in Hebei province.

Background: For patients who treated with tacrolimus after kidney transplant, therapeutic drug monitoring is essential to improve their prognosis. However, previous detection methods have limitations, such as the overestimation and unacceptable bias in the immunoassays. Precision medicine has been challenged. The liquid chromatography-tandem mass spectrometry (LC-MS/MS) method is recognized as the gold standard due to its accuracy and specificity, but lack of throughput and complex process limits its clinical application. Therefore, an accurate, simple and high throughput method for tacrolimus monitoring is needed for clinical practice. Methods: A modified LC-MS/MS method was introduced and validated. Whole blood samples were prepared by a one-step protein precipitation method. Chromatographic separation was achieved using a Phenomenex Kinetex 2.6 μm XB-C18 2.1 × 50 mm column with a total run time of 3.5 min to avoid matrix effect. An electrospray ionization source (ESI) was used in positive ion multiple reaction monitoring (MRM) mode for mass spectrometric detection. In order to protect the mass spectrometer, only part of the sample after LC separation was allowed to enter the mass spectrum, through a two HPLC systems coupled one mass spectrometry design. In this way, the instrument throughput is also improved and realizing the detection of 2 samples within 3.5 min and carried out a shorter analyzing time for each sample of 1.75 min. Additionally, we calculated tacrolimus-intrapatient variant (Tac-IPV) based on this modified method and assessed the prognostic value of Tac-IPV in Chinese kidney transplant patients. Results: The LC-MS/MS was modified by streamlining the procedure and increasing the throughput. The method proved to be accurate and reproducible with all performance parameters suitably meeting the clinical requirements over a calibration ranged from 0.37 to 42.90 ng/mL. Parameters such as linearity, limit of quantification (LoQ) and dilution integrity were validated with a clinical reportable range from 0.37 to 343.20 ng/mL, which was particularly useful for high drug concentrations patients (rare but very serious). Both cross-contamination and matrix effects were negligible. Clinical data of 83 patients showed that Tac-IPV was associated with poor kidney transplant outcome in Chinese (Hazard Ratio (HR) = 3.96, 4.75; 95% Cl: 1.10–14.21, 1.23–18.36; P < 0.05). Conclusions: This modified LC-MS/MS method possessed high throughput and simple sample preparation, allowing it to meet daily clinical needs. At the same time, Tac-IPV based on this modified LC-MS/MS had excellent prognostic value in kidney transplantation. These advantages have great significance for the individualized treatment of Chinese kidney transplant patients and broad application of Tac-IPV.

Seeking a scientific and reasonable population structure is the key to realizing low-carbon and green development of urban agglomerations. Based on the coupled coordination degree model and exploratory spatial data analysis (ESDA), this paper studied the spatiotemporal differences of population spatial equilibrium in Changsha-Zhuzhou-Xiangtan urban agglomeration, and constructed a nonlinear dynamic panel econometric model and quantile regression model to empirically test the carbon emission reduction effect and its heterogeneity of the population spatial equilibrium. The research conclusions are as follows: First, the population spatial equilibrium index of Changsha-Zhuzhou-Xiangtan urban agglomeration shows an upward trend in time, but the overall level is not high and the internal gap is obvious. In space, it presents a situation of concentration in the central urban area of Changsha. Second, the carbon emissions of Changsha-Zhuzhou-Xiangtan urban agglomeration have obvious dynamic inertia and path-dependent characteristics. That is, the carbon emissions of the previous period will significantly promote the carbon emissions of the current period. Third, the carbon emission reduction effect of population spatial equilibrium has the characteristics of an inverted “U” shape, and the population spatial equilibrium index in most areas is too low to achieve carbon emission reduction. Fourth, the legal environment helps to promote the spatial balance of population, thereby reducing the regional total carbon emissions, per capita carbon emissions and carbon emissions per unit area. Last, Changsha-Zhuzhou-Xiangtan urban agglomeration needs to improve the level of economic development and government expenditure to realize the carbon emission reduction effect. In general, Changsha-Zhuzhou-Xiangtan urban agglomeration should take into account the development of economy and environment in the process of improving the level of population space balance, so as to achieve a win-win situation for economy and environment.

On 6 February 2023 (UTC), an earthquake doublet, consisting of the Mw 7.8 Pazarcik earthquake and the Mw 7.5 Elbistan earthquake, struck south-central Turkey and northwestern Syria, which was the largest earthquake that occurred in Turkey since the 1939 Erzincan earthquake. The faulting model of this earthquake was estimated based on the coseismic InSAR and GPS displacements. In addition, the best-fitting coseismic faulting model indicates that both the Pazarcik earthquake and the Elbistan earthquake were controlled by predominated left-lateral strike-slip motion, with slip peaks of 9.7 m and 10.8 m, respectively. The Coulomb failure stress (CFS) change suggests that the Pazarcik earthquake has a positive effect in triggering the rupture of the seismogenic fault of the Elbistan earthquake. Furthermore, these two main shocks promoted the occurrence of the Mw 6.3 strong aftershock. Additionally, it is found that the 2023 Turkey-Syria earthquake doublet increased the rupture risk of the Puturge segment of the EAF fault and the northern segment of the Dead Sea Fault (DSF). It is crucial to note that the northern segment of the DSF has not experienced a large earthquake in several centuries, highlighting the need for heightened attention to the potential seismic hazard of this segment. Finally, a deformation zone adjacent to the DSF was identified, potentially attributed to the motion of a blind submarine fault.

The 2020 Mw 6.5 Stanley earthquake occurred in western North America and is the largest earthquake in Idaho state in the past ~40 yr. The hypocenter is located at the western margin of the Centennial Tectonic Belt (CTB), which is a subprovince of the Basin and Range and characterized by a series of normal faults. In this study, the coseismic Interferometric Synthetic Aperture Radar observations, geophysical data, and aftershocks are jointly collected to estimate the seismogenic fault of the 2020 Stanley earthquake. The best-fitting fault models suggest the earthquake occurred on two blind faults. Slip on the main, west-dipping, seismogenic fault was sinistral and on the second fault predominantly normal slip with a minor component of right-lateral strike slip. Geophysical observations including gravity and geomagnetic data are consistent with the fault interpretations. The Coulomb failure stress (CFS) change indicates that the rupture of the main seismogenic fault had a positive triggering effect on the slip of the second fault and may have increased the rupture risk of the Sawtooth fault. Moreover, a potential seismic hazard risk zone with a notably low occurrence of aftershocks is found in the west of the central segment of the main seismogenic fault. [ABSTRACT FROM AUTHOR]

Introduction: The risk of osteoporotic vertebral refracture (OVRF) is substantially increased after initial osteoporotic vertebral fracture (OVF). In this study, we comprehensively analyzed risk factors for OVRF in patients undergoing conservative treatment and further evaluated the predictive value of various risk factors. Methods: Basic information, past medical history and imaging parameters were collected from 151 postmenopausal OVFwomen treated conservatively. In univariate analysis, chi-square testwas used for categorical variables and independent sample t-test was used for continuous variables. Binary logistic regression was used to identify independent risk factors for variables with significant differences in univariate analysis. Then receiver operating characteristic curve analysis (ROC Curve) were drawn for the predictors and area under the curve (AUC) were calculated to evaluate the prediction accuracy. Results: Univariate analysis and binary logistic regression analysis showed that age (p < 0.05) and L3/4 paraspinal muscle fat infiltration ratio (FIR) (p < 0.05) were independent risk factors of OVRF. According to the ROC curve, the prediction accuracy of age, FIR and the two parameters together were 0.730, 0.778 and 0.813 respectively. The critical values of age and FIRwere 63.5 years and 37.1%, respectively. Conclusion: OVRF is affected by multiple factors. Age and FIR are independent risk factors of OVRF. The prediction value of integrated two independent risk factors was higher than that of a single risk factor. Postmenopausal women with initial OVF aged over 63.5 years and FIR over 37.1% were more likely to develop OVRF. [ABSTRACT FROM AUTHOR]

Gliomas are the most aggressive and common type of malignant brain tumor, with limited treatment options and a dismal prognosis. Angiogenesis, a hallmarks of cancer, is one of two critical events in the progression of gliomas. Accumulating evidence has demonstrated that in glioma dysregulated molecules like long noncoding RNAs (lncRNAs), are closely linked to tumorigenesis and prognosis. However, the effects of and mechanisms of action of lncRNAs during tumor angiogenesis are poorly understood. The effect of lncRNA RP11-732M18.3 on angiogenesis was elucidated through an intracranial orthotopic glioma model, immunohistochemistry, and an in vitro angiogenesis assay. Co-culture experiments and cell migration assays were performed to investigate the function of lncRNA RP11-732M18.3 in vitro. lncRNA RP11-732M18.3 increased CD31+ microvessel density, and overexpression of lncRNA RP11-732M18.3 resulted in poor mouse survival. lncRNA RP11-732M18.3 promoted endothelial cell migration and tube formation. Nomogram and Kaplan-Meier survival analyses indicated that higher VEGFA is correlated with a poor prognosis. Mechanistically, lncRNA RP11-732M18.3 promotes angiogenesis by increasing the nuclear level of EP300 and facilitating the transcription and secretion of VEGFA. Our study contributes to the latest understanding of glioma angiogenesis and prognosis. lncRNA RP11-732M18.3 may be a potential treatment target in glioma.

AIM: To investigate the early corneal morphological changes and the possible influenced factors of small incision lenticule extraction(SMILE)combined with corneal collagen cross-linking(CXL)in the treatment of refractive error.METHODS: This was a retrospective case study. The patients(76 eyes)with ametropia who had undergone SMILE surgery in our hospital from September 2018 to March 2019 were small age, high degree of severity, thin cornea or irregular shape. The patients were divided into the SMILE combined with CXL group with 17 patients(32 eyes)and the SMILE group with 22 patients(44 eyes). The corneal morphological parameters of the two groups were measured preoperatively and 1mo postoperatively. RESULTS: There were significant statistically differences in the changes of K1, K2, Km, central corneal thickness, posterior corneal elevation, anterior corneal elevation parameters, posterior corneal elevation parameters, the D value and index of vertical asymmetry(IVA)between these two groups(PP>0.05). The changes of some parameters of the corneal anterior surface morphology of the two groups were correlated with the corneal cutting depth, spherical equivalent and optical zone diameter(PP>0.05). There was no apparent correlation between the changes of corneal surface morphology and the cross-linking depthin SMILE combined with CXL group(P>0.05). CONCLUSION: SMILE combined with CXL was applied to the high-risk patients with small age, high degree of severity, thin cornea or irregular shape, which increased its safety and effectiveness. SMILE combined with CXL didn't make significant effects on the posterior surface morphology of the cornea, but it influenced the anterior surface morphology. The influenced factors may be related to the corneal cutting depth, the spherical equivalent and the optical zone diameter.

Abstract Background Clinically, the median survival in patients with metastatic renal cell carcinoma (RCC) was only 6–12 months and a 5-year survival rate of less than 20%. Therefore, an in-depth study of the molecular mechanisms involved in RCC is of great significance for improving the survival of patients with advanced RCC. Acylglycerol kinase (AGK) is a newly discovered lipid kinase that has been reported to be a potent oncogene that may be involved in the regulation of malignant progression in a variety of tumours. However, the expression and biological characteristics of the AGK gene in RCC remain unclear. Methods AGK expression was quantified by quantitative real-time PCR, Western blotting and immunohistochemistry in RCC cell lines and paired patient tissues. Kaplan-Meier method and Cox proportional hazards models were used to evaluate the prognostic value of AGK in human RCC tissue samples. Chi-squared test was performed to analyse the correlation between AGK expression and the clinicopathological features. Stable overexpression and knockdown of AGK in RCC cells was constructed with lentivirus. The oncogenic effects of AGK in human RCC progression were investigated using assays of colony formation, anchorage-independent growth, EdU assay, cell cycle analysis, wound-healing, trans-well analysis and xenograft tumour model. GSEA and KEGG analysis were conducted to detect the potential pathway of AGK involved in RCC. These results were further confirmed using the luciferase reporter assays, immunofluorescence and in vivo experiments. Results AGK expression is significantly elevated in RCC and closely related to the malignant development and poor prognosis in RCC patients. By in vitro and in vivo experiments, AGK was shown to enhance the proliferation of RCC cells by promoting the transition from the G1 phase to the S phase in the cell cycle and to enhance the migration and invasion by promoting epithelial-mesenchymal transition. By activating the PI3K/AKT/GSK3β signalling pathway in RCC, AGK can increase nuclear accumulation of β-catenin, which further upregulated TCF/LEF transcription factor activity. Conclusions AGK promotes the progression of RCC via activating the PI3K/AKT/GSK3β signalling pathway and might be a potential target for the further research of RCC.

Potassium (K) use efficiency in Paris polyphylla var. yunnanensis production is relatively low, and the excessive use of K fertilization has negative environmental impacts. Bacterial isolates can effectively alleviate this situation. The present work aimed to analyze the effects of different combinations of three potassium-solubilizing bacteria (KSB) (Bacillus thuringiensis, B. polymyxa, and Paenibacillus amylolyticus) on K in soil and P. polyphylla var. yunnanensis. The results showed that the contents of different forms of K were increased after the application of KSB. Compared with the control group, the maximum increases of slow-acting K, available K, quick-acting K, exchangeable K, and water-soluble K were 32.6% under inoculation with both P. amylolyticus and B. polymyxa, 73.5% with B. thuringiensis, 114.0% with B. thuringiensis, 83.2% with P. amylolyticus, and 210.0% with B. thuringiensis, respectively. This promoted the conversion of soil K to the form of K with high plant availability. Pseudo-protodiosgenin and diosgenin H contents were improved by KSB inoculations, which promoted medicinal quality of P. polyphylla var. yunnanensis. Correlation analysis showed that there were significantly positive correlations among the five forms of K in the soil in all experimental groups. In conclusion, the inoculation of KSB effectively improved the plant availability of soil K and medicinal quality of P. polyphylla var. yunnanensis, providing a path for sustainable production of P. polyphylla var. yunnanensis.

Abstract Background The chromosomal 15q11‐q13 regions are structurally complex, and their abnormalities are associated with various neuropsychiatric disorders, including autism spectrum disorder (ASD), epilepsy, Angelman syndrome, and Prader–Willi syndrome. Case description A 6‐year‐old child was admitted to the hospital as a result of an “epileptic status” showing ASD, intractable epilepsy, and total developmental retardation. Chromosome gene detection showed repetitive variation in the 15q11‐q13 regions, and the video electroencephalogram was abnormal. Although children are currently given antiepileptic treatment and rehabilitation training, intermittent seizures can still occur. Conclusion The clinical phenotypes of 15q11‐q13 repetitive syndrome are complex, and vary in severity. Children with intractable epilepsy, ASD, and language and motor retardation should be considered to have this syndrome, which requires confirmation by multiplex ligation‐dependent probe amplification and gene detection. These approaches can enable early rehabilitation treatment and improve the patients’ quality of life.

Abstract Background A sequential combination of radiochemotherapy/endocrinotherapy and cytokine-induced killer cell (CIK) infusion has been shown to be an effective therapy for post-mastectomy breast cancer based on statistical analysis of the patient population. However, whether an individual could obtain an improved prognosis from CIK cell-based treatment remains unknown. In the present study, we focused on immune microenvironment regulation and specifically investigated the relationship between PD-L1 expression and survival benefit from CIK immunotherapy in breast cancer. Methods A total of 310 postoperative breast cancer patients who received comprehensive treatment were enrolled in this retrospective study, including 160 patients in the control group (received chemotherapy/radiotherapy/endocrinotherapy) and 150 patients in the CIK cell treatment group (received chemotherapy/radiotherapy/ endocrinotherapy and subsequent CIK infusion). Results We found that overall survival (OS) and recurrence-free survival (RFS) were significantly better in the CIK group than that in the control group. PD-L1 expression in tumor tissue sections was showed to be an independent prognostic factor for patients in the CIK treatment group using multivariate survival analysis. Further survival analysis in the CIK group showed that patients with PD-L1 tumor expression exhibited longer OS and RFS. In addition, among all patients who were enrolled in this study, only the patients with PD-L1 expression experienced survival benefits from CIK treatment. Conclusions Our study showed the relationship between PD-L1 expression and CIK therapy and revealed that PD-L1 expression in the tumor is as an indicator of adjuvant CIK therapy for postoperative breast cancer.

Background: Long noncoding RNAs (lncRNAs) have been identified as regulators of a number of developmental and tumorigenic processes. However, the functions of most lncRNAs in glioma remain unknown and the mechanisms governing the proliferation of tumor cells remain poorly defined. Methods: Both in vitro and in vivo assays were performed to investigate the roles of lncRNAs in the pathophysiology of gliomas. lncRNA arrays were used to identify differentially expressed lncRNAs. Subcutaneous tumor formation and a brain orthotopic tumor model in nude mice were used to investigate the functions of lncRNAs in vivo. The in vitro functions of lncRNAs were analyzed by fluorescence-activated cell sorting, colony formation, and western blot analyses. RNA fluorescence in situ hybridization and immunoprecipitation were used to explore the underlying mechanisms. Findings: Here, we describe the newly discovered noncoding RNA RP11-732M18.3, which is highly overexpressed in glioma cells and interacts with 14-3-3β/α to promote glioma growth, acting as an oncogene. Overexpression of lncRNA RP11-732 M18.3 was associated with the proliferation of glioma cells and tumor growth in vitro and in vivo. Remarkably, lncRNA RP11-732M18.3 promoted cell proliferation and G1/S cell cycle transition. lncRNA RP11-732M18.3 is predominately localized in the cytoplasm. Mechanistically, the interaction of lncRNA RP11-732M18.3 with 14-3-3β/α increases the degradation of the p21 protein. lncRNA RP11-732M18.3 promoted the recruitment of ubiquitin-conjugating enzyme E2 E1 to 14-3-3β/α and the binding of 14-3-3β/α with ubiquitin-conjugating enzyme E2 E1 (UBE2E1) promoted the degradation of p21. Interpretation: Overall these data demonstrated that lncRNA RP11-732M18.3 regulates glioma growth through a newly described lncRNA-protein interaction mechanism. The inhibition of lncRNA RP11-732M18.3 could provide a novel therapeutic target for glioma treatment. Keywords: lncRNA RP11-732M18.3, 14-3-3β/α, p21, Tumorigenesis, Glioma

Abstract Background In our previous study, we identified a candidate tumor suppressor gene, testin LIM domain protein (TES), in primary gastric cancer (GC). TES contains three LIM domains, which are specific interacting regions for the cell adhesion and cytoskeleton regulatory proteins. Mena is a known cytoskeleton regulator that regulates the assembly of actin filaments and modulates cell adhesion and motility by interacting with Lamellipodin (Lpd). Therefore, we hypothesized that TES plays a role as tumor suppressor in GC through interacting with Mena. This study aimed to investigate the tumor suppressive functions of TES in GC. Methods We explored the tumor suppressive effect of TES in GC by in vitro cell proliferation assay, colony formation assay, cell cycle analysis, Transwell assays, and in vivo tumorigenicity and metastasis assays. The interaction of TES and Mena was investigated through immunoprecipitation-based mass spectrometry. We also analyzed the expression of TES and Mena in 172 GC specimens using immunohistochemistry and investigated the clinicopathological and prognostic significance of TES and Mena in GC. Results TES suppressed GC cell proliferation and colony formation, induced cell cycle arrest, and inhibited tumorigenicity in vitro. Additionally, it inhibited GC cell migration and invasion in vitro and suppressed metastasis in vivo. TES interacted with Mena, and inhibited the interaction of Mena with Lpd. Transwell assays suggested that TES suppressed migration and invasion of GC cells in a Mena-dependent fashion. In GC patients with high Mena expression, the expression of TES was associated with tumor infiltration (P = 0.005), lymph node metastasis (P = 0.003), TNM stage (P = 0.003), and prognosis (P = 0.010). However, no significant association was observed in GC patients with low Mena expression. Conclusions We believe that TES functions as a Mena-dependent tumor suppressor. TES represents a valuable prognostic marker and potential target for GC treatment.

Background The advent of immune checkpoint therapy has been a tremendous advance in cancer treatment. However, the responses are still insufficient in patients with soft tissue sarcoma (STS). We aimed to identify rational combinations to increase the response to immune checkpoint therapy and improve survival.Methods Whole-exome sequencing (WES) was performed in 11 patients with liposarcoma. Somatic copy number alterations (SCNAs) were analyzed at the gene level to identify obvious amplification patterns in drug-target genes. The expression and prognostic value of class I histone deacetylases (HDACs) was evaluated in 49 patients with sarcoma in our center and confirmed in 263 sarcoma samples from The Tumor Cancer Genome Atlas (TCGA) database. Q-PCR, flow cytometry and RNA-seq were performed to determine the correlations between class I HDACs, chidamide and PD-L1 in vitro and in vivo. The efficacy of combining chidamide with PD-1 blockade was explored in an immunocompetent murine model and a small cohort of patients with advanced sarcoma. Western blot, ChIP assay and dual luciferase assessment were applied in the mechanistic study.Results The HDAC gene family was frequently amplified in STS. SCNAs in the HDAC gene family were extensively amplified in 8 of 11 (73%) patients with liposarcoma, based on a drug-target gene set, and we verified amplification in 76.65% (197/257) of cases by analyzing TCGA sarcoma cohort. Class I HDAC expression is associated with a poor prognosis for patients with STS, and its inhibition is responsible for promoting apoptosis and upregulating of programmed cell death ligand 1 (PD-L1). The HDAC class I inhibitor chidamide significantly increases PD-L1 expression, increased the infiltration of CD8+ T cells and reduced the number of MDSCs in the tumor microenvironment. The combination of chidamide with an anti-PD-1 antibody significantly promotes tumor regression and improves survival in a murine model. Moreover, chidamide combined with the anti-PD-1 antibody toripalimab is effective in patients with advanced and metastatic sarcoma, and the side effects are tolerable. Mechanistically, chidamide increases histone acetylation at the PD-L1 gene through the activation of the transcriptional factor STAT1.Conclusions The combination of chidamide and anti-programmed cell death 1 (PD-1) therapy represents a potentially important strategy for STS.

Abstract Objectives Although axitinib has achieved a preferable response rate for advanced renal cell carcinoma (RCC), patient survival remains unsatisfactory. In this study, we evaluated the efficacy and safety of a combination treatment of axitinib and a low dose of pembrolizumab‐activated autologous dendritic cells–co‐cultured cytokine‐induced killer cells in patients with advanced RCC. Methods All adult patients, including treatment‐naive or pretreated with VEGF‐targeted agents, were enrolled from May 2016 to March 2019. Patients received axitinib 5 mg twice daily and pembrolizumab‐activated dendritic cells–co‐cultured cytokine‐induced killer cells intravenously weekly for the first four cycles, every 2 weeks for the next four cycles, and every month thereafter. Results The 43 patients (22 untreated and 21 previously treated) showed a median progression‐free survival (mPFS) of 14.7 months (95% CI, 11.16–18.30). mPFS in treatment‐naive patients was 18.2 months, as compared with 14.4 months in pretreated patients (log‐rank P‐value = 0.07). Overall response rates were 25.6% (95% CI, 13.5–41.2%). Grade 3 or higher adverse events occurred in 5% of patients included hypertension (11.6%) and palmar‐plantar erythrodysesthesia (7.0%). Peripheral blood lymphocyte immunophenotype and serum cytokine profile analyses demonstrated increased antitumor immunity after combination treatment particularly in patients with a long‐term survival benefit, while those with a minimal survival benefit demonstrated an elevated proportion of peripheral CD8+TIM3+ T cells and lower serum‐level immunostimulatory cytokine profile. Conclusions The combination therapy was active and well tolerated for treatment of advanced RCC, either as first‐ or second‐line treatment following other targeted agents. Changes in immunophenotype and serum cytokine profile may be used as prognostic biomarkers.

Abstract Background Homozygous spinocerebellar ataxia type 3 (SCA3) patients, which have an expanded cytosine‐adenine‐guanine (CAG) repeat mutation in both alleles of ATXN3, are extremely rare. Clinical features and genetic characteristics of them were seldom studied. Methods We analyzed seven newly homozygous SCA3 patients from five families and 14 homozygotes reported previously. An additional cohort of 30 heterozygous SCA3 patients were analyzed to compare age at onset (AAO). Results Two out of seven SCA3 homozygotes had the minimum CAG repeats reported so far (55/56 and 56/58). Five patients appeared peripheral neuropathy and two had mild cognitive impairment. The AAO was significantly inversely correlated with both the large and small expanded CAG repeats (r = −.7682, p

Adjuvant chemotherapy after surgery is the standard treatment modality for stage III and part of stage II or stage IV colorectal cancer (CRC) patients. However, the 5-year overall survival (OS) rate remains unsatisfactory. Thus, developing combination therapies is essential to improve the prognosis of patients with CRC. The present study aimed to determine the effect of a sequential combination of cytokine-induced killer cell (CIK) infusion and chemotherapy for patients with CRC. 122 patients with CRC treated with postoperative adjuvant chemotherapy were retrospectively included in this study. Among them, 62 patients received adjuvant chemotherapy only (control group), while the other 60 patients, with similar demographic and clinical characteristics, received adjuvant chemotherapy and sequential CIK cell immunotherapy (CIK group). Survival analysis showed significantly improved disease free survival (DFS) and OS rates in the CIK group compared with the control group (log-rank test, P = .0024; P = .008, respectively). Univariate and multivariate analyses indicated that sequential CIK cell treatment was an independent prognostic factor for patients’ DFS and OS. Subgroup analyses showed that sequential CIK cell treatment significantly improved the DFS and OS of patients with high-risk T4 stage and insufficient chemotherapy duration. In conclusion, these data indicate that sequential adjuvant CIK cell treatment combined with chemotherapy is an effective therapeutic strategy to prevent disease recurrence and prolong survival of patients with CRC, particularly for patients with high-risk T4 stage and insufficient chemotherapy duration.

Abstract Objectives Fluoropyrimidine‐based chemotherapy regimens are the current first‐line treatment for metastatic colorectal cancer (mCRC); however, the outcome is often unsatisfactory. The present study aimed to determine the effect of combined cytokine‐induced killer (CIK) cell immunotherapy and first‐line chemotherapy in patients with mCRC. Methods This retrospective study included 252 patients with mCRC treated with first‐line chemotherapy. Among them, 126 patients received first‐line chemotherapy only (control group), while the other 126 patients, with similar demographic and clinical characteristics, received CIK cell immunotherapy combined with first‐line chemotherapy (CIK group). Overall survival (OS) and progression‐free survival (PFS) were compared between the two groups using the Kaplan–Meier method. Results The median OS for the CIK group was 54.7 versus 24.1 months for the controls, and the median PFS for the CIK group was 25.7 versus 14.6 months for the controls. Univariate and multivariate analyses indicated that CIK cell treatment was an independent prognostic factor for patients' OS and PFS. Subgroup analyses showed that CIK cell treatment significantly improved the OS and PFS of patients with metastatic colon cancer, but not those with metastatic rectal cancer. Additionally, the change in CD3+CD56+ subsets after the fourth treatment cycle might be an indicator of successful CIK cell treatment: Patients with increased CD3+CD56+ subsets had better survival than those with decreased CD3+CD56+ subsets. Conclusion Cytokine‐induced killer cell immunotherapy combined with first‐line chemotherapy could significantly improve the OS and PFS of patients with mCRC, particularly for patients with metastatic colon cancer.

Abstract The levels of decoy receptor 3 (DcR3), soluble urokinase type plasminogen activator receptor (suPAR) and procalcitonin (PCT) are significantly increased in sepsis. We investigated the diagnostic value of DcR3 combined with suPAR and PCT in sepsis. Patients with sepsis, non-infectious systemic inflammatory response comprehensive syndrome (SIRS) and healthy controls were recruited according to the diagnostic standard. We measured DcR3, suPAR, PCT, interleukin-6 (IL-6) and C-reactive protein (CRP), and the diagnostic value was evaluated by receiver operating characteristics (ROC) curves. In our analysis, serum DcR3, suPAR and PCT levels of the sepsis group were significantly higher than those of the SIRS and control groups. However, IL-6, CRP and WBC showed no significant difference between the SIRS group and the sepsis group. The serum DcR3 level was positively correlated with the serum suPAR level (r = 0.37, p = 0.0022) and PCT level (r = 0.37, p = 0.0021). Using DcR3, suPAR and PCT to distinguish SIRS from sepsis, the area under the curve (AUC) values were 0.892, 0.778 and 0.692. When DcR3, suPAR and PCT combined were used for diagnosis of sepsis, the AUC was 0.933, at a cut-off point of 0.342. This combination improved the sensitivity and specificity of diagnosis of sepsis, suggesting that use of the combination of three indexes enhanced the efficiency of sepsis diagnosis.

Flavonoids from Huangqin (dried roots of Scutellaria baicalensis Georgi) have anti-inflammatory effects, and are considered useful for treatment of spinal cord injury. To verify this hypothesis, the T9–10 spinal cord segments of rats were damaged using Allen's method to establish a rat spinal cord injury model. Before model establishment, Huangqin flavonoid extraction (12.5 g/kg) was administered intragastrically for 1 week until 28 days after model establishment. Methylprednisolone (30 mg/kg) was injected into the tail vein at 30 minutes after model establishment as a positive control. Basso, Beattie, and Bresnahan locomotor scale scores were used to assess hind limb motor function. Hematoxylin-eosin staining was used to detect pathological changes in the injured spinal cord. Immunofluorescence and western blot assays were performed to measure immunoreactivity and expression levels of brain-derived neurotrophic factor, neuronal marker neurofilament protein, microglial marker CD11b and astrocyte marker glial fibrillary acidic protein in the injured spinal cord. Huangqin flavonoid extraction markedly reduced spinal cord hematoma, inflammatory cell infiltration and cavities and scars, and increased the Basso, Beattie, and Bresnahan locomotor scale scores; these effects were identical to those of methylprednisolone. Huangqin flavonoid extraction also increased immunoreactivity and expression levels of brain-derived neurotrophic factor and neurofilament protein, and reduced immunoreactivity and expression levels of CD11b and glial fibrillary acidic protein, in the injured spinal cord. Overall, these data suggest that Huangqin flavonoid extraction can promote recovery of spinal cord injury by inducing brain-derived neurotrophic factor and neurofilament protein expression, reducing microglia activation and regulating reactive astrocytes.

Background: Remote ischemic postconditioning (RIPostC) appears to protect distant organs from ischemia-reperfusion injury (IRI). However, cerebral protection results have remained inconclusive. In the present study, a meta-analysis was performed to compare stroke patients with and without RIPostC. Methods: CNKI, WanFang, VIP, CBM, PubMed, and Cochrane Library databases were searched up to July 2016. Data were analyzed using both fixed-effects and random-effects models by Review Manager. For each outcome, risk ratio (RR) and mean difference (MD) with 95% confidence interval (CI) were calculated. Results: A total of 13 randomized controlled trials that enrolled a total of 794 study participants who suffered from or are at risk for brain IRI were selected. Compared with controls, RIPostC significantly reduced the recurrence of stroke or transient ischemic attacks (RR = 0.37; 95% CI: 0.26–0.55; P < 0.00001). Moreover, it can reduce the levels of the National Institutes of Health Stroke Scale score (MD: 1.96; 95% CI: 2.18–1.75; P < 0.00001), modified Rankin Scale score (MD: 0.73; 95% CI: 1.20–0.25; P = 0.00300), and high-sensitivity C-reactive protein (MD: 4.17; 95% CI: 4.71–3.62; P < 0.00001) between the two groups. There was no side effect of RIPostC using tourniquet cuff around the limb on ischemic stroke treating based on different intervention duration. Conclusion: The present meta-analysis suggests that RIPostC might offer cerebral protection for stroke patients suffering from or are at risk of brain IRI.

Sentinel-1 Terrain Observation by Progressive Scans (TOPS) data have been widely applied in earthquake studies due to their open-source policy, short revisit cycle and wide coverage. However, significant near-fault displacement gradients and the moderate azimuth resolution of TOPS data make achieving high-precision along-track measurements challenging, which prevents the generation of high-quality three-dimensional (3D) displacement maps. Here, we propose an integrated method to retrieve high-quality 3D displacements based on the differential interferometric SAR (DInSAR), burst-overlap interferometry (BOI), multiple-aperture InSAR (MAI) and pixel offset tracking (POT) techniques, which are achieved to use only two track Sentinel-1 TOPS data with different viewing geometries. The key step of this method is using a weighted fusion algorithm with the interpolated BOI-derived and MAI-derived 3D displacements. In a case study of the 2021 Maduo earthquake, the calculated root mean square errors (RMSEs) from global navigation satellite system (GNSS) data and the InSAR-derived 3D displacement fields were found to be 6.3, 5.8 and 1.7 cm in north–south, east–west and up–down components, respectively. Moreover, the slip model of the 2021 Maduo earthquake jointly estimated by DInSAR and BOI measurements indicates that this seismic event was dominated by sinistral strike-slip motion mixed with some dip-slip movements; the estimated seismic moment was 1.75 × 1020 Nm, corresponding to a Mw 7.44 event.

The protein p53 is one of the most important tumor suppressors, responding to a variety of stress signals. Mutations in p53 occur in about half of human cancer cases, and dysregulation of the p53 function by epigenetic modifiers and modifications is prevalent in a large proportion of the remainder. PRMT1 is the main enzyme responsible for the generation of asymmetric-dimethylarginine, whose upregulation or aberrant splicing has been observed in many types of malignancies. Here, we demonstrate that p53 function is regulated by PRMT1 in breast cancer cells. PRMT1 knockdown activated the p53 signal pathway and induced cell growth-arrest and senescence. PRMT1 could directly bind to p53 and inhibit the transcriptional activity of p53 in an enzymatically dependent manner, resulting in a decrease in the expression levels of several key downstream targets of the p53 pathway. We were able to detect p53 asymmetric-dimethylarginine signals in breast cancer cells and breast cancer tissues from patients, and the signals could be significantly weakened by silencing of PRMT1 with shRNA, or inhibiting PRMT1 activity with a specific inhibitor. Furthermore, PRMT1 inhibitors significantly impeded cell growth and promoted cellular senescence in breast cancer cells and primary tumor cells. These results indicate an important role of PRMT1 in the regulation of p53 function in breast tumorigenesis.

Abstract Background Reduced expression of tripartite motif-containing 3 (TRIM3) has been reported to be involved in the pathogenesis of human glioblastoma. In our previous research, we found that TRIM3 expression was markedly reduced in human primary hepatocellular carcinoma (HCC) tissues and that low TRIM3 expression was associated with short survival of HCC patients. However, the role of TRIM3 in liver cancer remains unknown. This study aimed to investigate the function of TRIM3 in liver cancer cells. Methods The protein levels of TRIM3 in five liver cancer cell lines (SK-Hep1, Hep3B, Huh7, HepG2, Bel-7402) and one normal liver cell line (L02) were detected with Western blotting. HepG2 and Bel-7402 cells with low TRIM3 expression were infected with recombinant lentiviruses overexpressing TRIM3 (LV-TRIM3), whereas Huh7 and Hep3B cells with high TRIM3 expression were transfected with TRIM3-targeted small interfering RNA (siTRIM3). The functions of TRIM3 in the proliferation, colony formation, cell cycle, migration, invasion, and apoptosis of the above cell lines were examined. The effect of TRIM3 on tumor growth and metastases in nude mice was also investigated. Results TRIM3 was overexpressed in HepG2 and Bel-7402 cells with LV-TRIM3 infection, which further reduced proliferation, colony formation, migration, and invasion of both cell lines. Cell cycle analysis showed that TRIM3 overexpression induced G0/G1 phase arrest in HepG2 and Bel-7402 cells. Moreover, apoptosis was not increased in HepG2 or Bel-7402 cells overexpressing TRIM3. Contrarily, silencing TRIM3 expression in Huh7 and Hep3B cells by siTRIM3 led to significantly decreased percentages of both cells in the G0/G1 phase and promoted cell proliferation, colony formation, migration, and invasion. In vivo experiment results confirmed that TRIM3 overexpression suppressed tumor growth and metastasis. Conclusions TRIM3 plays a tumor-suppressing role in the regulation of liver cancer development by reducing cell proliferation through cell cycle arrest at the G0/G1 phase.

Accumulated evidence shows that vanin-1 (VNN1) plays a key part in glucose metabolism. We explored the effect of VNN1 on cholesterol metabolism, inflammation, apoptosis in vitro, and progression of atherosclerotic plaques in apoE−/− mice. Oxidized LDL (Ox-LDL) significantly induced VNN1 expression through an ERK1/2/cyclooxygenase-2/PPARα signaling pathway. VNN1 significantly increased cellular cholesterol content and decreased apoAI and HDL-cholesterol (HDL-C)-mediated efflux by 25.16% and 23.13%, respectively, in THP-1 macrophage-derived foam cells (P < 0.05). In addition, VNN1 attenuated Ox-LDL-induced apoptosis through upregulation of expression of p53 by 59.15% and downregulation of expression of B-cell lymphoma-2 127.13% in THP-1 macrophage (P < 0.05). In vivo, apoE−/− mice were divided randomly into two groups and transduced with lentivirus (LV)-Mock or LV-VNN1 for 12 weeks. VNN1-treated mice showed increased liver lipid content and plasma levels of TG (124.48%), LDL-cholesterol (119.64%), TNF-α (148.74%), interleukin (IL)-1β (131.81%), and IL-6 (156.51%), whereas plasma levels of HDL-C (25.75%) were decreased significantly (P < 0.05). Consistent with these data, development of atherosclerotic lesions was increased significantly upon infection of apoE−/− mice with LV-VNN1. These observations suggest that VNN1 may be a promising therapeutic candidate against atherosclerosis.

To the cataract patient after corneal refractive surgery, if the intraocular lens power was determined by conventional formulas, different refractive errors may be produced after intraocular lens implantation. This inaccuracy of the lens power mainly came from 2 aspects-errors of corneal refractive power measurement and errors of formulas. Besides, imprecise of ocular axial length measurement and invalid lens position calculation also contributed to the inaccuracy of lens power. Therefore, in order to reduce refractive errors of cataractous surgery in patient underwent refractive surgery, appropriate method should be used to estimate the refractive power of corneal, and proper formula should be selected to calculate intraocular lens power.

Cytokine-induced killer (CIK) cells that are stimulated using mature dendritic cells (DCs), referred to as (DC-CIK cells) exhibit superior anti-tumor potency. Anti-programmed death-1 (PD-1) antibodies reinvigorate T cell-mediated antitumor immunity. This phase I study aimed to assess the safety and clinical activity of immunotherapy with PD-1 blockade (pembrolizumab)-activated autologous DC-CIK cells in patients with advanced solid tumors. Patients with selected types of advanced solid tumors received a single intravenous infusion of activated autologous DC-CIK cells weekly for the first month and every 2 weeks thereafter. The primary end points were safety and adverse event (AE) profiles. Antitumor responses, overall survival (OS), progression-free survival (PFS) and cytolytic activity were secondary end points. Treatment-related AEs occurred in 20/31 patients. Grade 3 or 4 toxicities, including fever and chills, were observed in two patients. All treatment-related AEs were reversible or controllable. The cytotoxicity of DC-CIK cells induced up-regulation of PD-L1 expression on autologous tumor cells. When activated using pembrolizumab ex vivo, DC-CIK cells exerted superior antitumor properties and elevated IFN-γ secretion. Objective responses (complete or partial responses) were observed in 7 of the 31patients.These responses were durable, with 6 of 7 responses lasting more than 5 months. The overall disease control rate in the patients was 64.5%. At the time of this report, the median OS and PFS were 270 and 162 days, respectively. In conclusions, treatment with pembrolizumab-activated autologous DC-CIK cells was safe and exerted encouraging antitumor activity in advanced solid tumors. A larger phase II trial is warranted.

Interleukin (IL)-17 has been reported to play a controversial role in tumor immunity. Our previous studies showed that infiltration of IL-17-producing cells in esophageal squamous cell carcinoma (ESCC) induced tumor protective immunity by recruiting CD8+T lymphocytes, natural killer (NK) cells, and B lymphocytes into the tumor microenvironment. However, the mechanism of IL-17 regulation of tumor-associated neutrophils remains elusive in ESCC. In this study, we therefore evaluated the accumulation of myeloperoxidase (MPO)+ neutrophils and its association with IL-17-producing cells within ESCC tumor nests. We also investigated the effects of IL-17 on the recruitment and antitumor activity of neutrophils. MPO+ neutrophil infiltration was found to predict a favorable prognosis in ESCC patients and was positively correlated with IL-17+ cell density. IL-17 stimulated ESCC tumor cells to release more of the CXC chemokines CXCL2 and CXCL3, which are involved in neutrophil migration. Furthermore, IL-17 potentiates the direct killing capability of neutrophils by enhancing the production of cytotoxic molecules, including reactive oxygen species (ROS), MPO, TNF-related apoptosis-inducing ligand (TRAIL), and IFN-γ. Experiments in mice suggested that IL-17 alone might not affect tumor progression in the tumor-bearing host, but IL-17 can inhibit tumor growth by promoting beneficial neutrophil infiltration and activation at tumor sites. As emerging evidence indicates that targeting tumor-associated neutrophils is a strategy for antitumor therapy, our findings reveal a positive contribution of IL-17 to the modulation of neutrophil-mediated antitumor immunity in ESCC. This study provides further understanding of the mechanisms that selectively regulate functional activities of neutrophils, which may be critical for developing new tumor immunotherapy.