The role of USP7-YY1 interaction in promoting colorectal cancer growth and metastasis.

Colorectal cancer (CRC) remains a significant global health issue with high incidence and mortality. Yin Yang 1 (YY1) is a powerful transcription factor that acts dual roles in gene activation and repression. High expression level of YY1 has been reported in CRC, indicating the existence of stable factors of YY1 in CRC cells. We aimed to identify the key molecules and underlying mechanisms responsible for stabilizing YY1 expression in CRC. Mass spectrometry analysis was utilized to identify USP7 as a potential molecule that interacted with YY1. Mechanically, USP7 stabilizes YY1 expression at the protein level by interfering its K63 linkage ubiquitination. YY1 exerts its oncogenic function through transcriptionally activating TRIAP1 but suppressing LC3B. In addition, at the pathological level, there is a positive correlation between the expression of YY1 and the budding of CRC. This study has revealed the intricate interplay between YY1 and USP7 in CRC, suggesting that they could serve as novel therapeutic targets or predictive biomarkers for CRC patients.

The efficacy of immune checkpoint inhibitors on low PD-L1 cervical cancer: A meta-analysis.

Background and Aims: The effectiveness of immune checkpoint inhibitors (ICIs) in low programmed death ligand 1 (PD-L1) expression in cervical cancer (CC) patients remains unknown. We aimed to evaluate the efficacy of ICIs in low PD-L1 expression CC patients. Methods: The study is an individual patient data (IPD)-based meta-analysis. IPD were compiled through KMSubtraction and IPDfromKM methodologies from high-quality randomized clinical trials and single-arm studies which reported overall survival (OS) or progression-free survival (PFS) stratified by PD-L1 expression. Kaplan-Meier curves and Cox regression analysis were employed to evaluate the survival benefits of ICIs. Results: A total of eight studies and 1110 cases were included in the analysis. Within the low PD-L1 expression subgroup, ICI combination therapy, but not ICI monotherapy, demonstrated significant OS benefits over non-ICI treatment (hazard ratio [HR] = 0.61, 95% confidence interval [CI]: 0.36-1.04, p = 0.06). Concerning PFS, ICI monotherapy was associated with a negative effect compared to non-ICI treatment (HR = 4.59, 95% CI: 2.32-9.07, p < 0.001). Notably, both OS and PFS outcomes were unfavorable for ICI monotherapy compared to both non-ICI and ICI combination therapy in the combined positive score <1 subgroup (OS: HR = 2.60, 95% CI: 1.31-5.16, p = 0.008; PFS: HR = 7.59, 95% CI: 3.53-16.31, p < 0.001). Conclusion: In patients with CC and low PD-L1 expression, ICI monotherapy may not be considered as the optimal treatment strategy when compared to non-ICI treatment or ICI combination therapy. Registration: CRD42023395103.

Metagenomic insights into the response of soil microbial communities to pathogenic Ralstonia solanacearum.

Understanding the response of soil microbial communities to pathogenic Ralstonia solanacearum is crucial for preventing bacterial wilt outbreaks. In this study, we investigated the soil physicochemical and microbial community to assess their impact on the pathogenic R.solanacearum through metagenomics. Our results revealed that certain archaeal taxa were the main contributors influencing the health of plants. Additionally, the presence of the pathogen showed a strong negative correlation with soil phosphorus levels, while soil phosphorus was significantly correlated with bacterial and archaeal communities. We found that the network of microbial interactions in healthy plant rhizosphere soils was more complex compared to diseased soils. The diseased soil network had more linkages, particularly related to the pathogen occurrence. Within the network, the family Comamonadaceae, specifically Ramlibacter_tataouinensis, was enriched in healthy samples and showed a significantly negative correlation with the pathogen. In terms of archaea, Halorubrum, Halorussus_halophilus (family: Halobacteriaceae), and Natronomonas_pharaonis (family: Haloarculaceae) were enriched in healthy plant rhizosphere soils and showed negative correlations with R.solanacearum. These findings suggested that the presence of these archaea may potentially reduce the occurrence of bacterial wilt disease. On the other hand, Halostagnicola_larseniia and Haloterrigena_sp._BND6 (family: Natrialbaceae) had higher relative abundance in diseased plants and exhibited significantly positive correlations with R.solanacearum, indicating their potential contribution to the pathogen's occurrence. Moreover, we explored the possibility of functional gene sharing among the correlating bacterial pairs within the Molecular Ecological Network. Our analysis revealed 468 entries of horizontal gene transfer (HGT) events, emphasizing the significance of HGT in shaping the adaptive traits of plant-associated bacteria, particularly in relation to host colonization and pathogenicity. Overall, this work revealed key factors, patterns and response mechanisms underlying the rhizosphere soil microbial populations. The findings offer valuable guidance for effectively controlling soil-borne bacterial diseases and developing sustainable agriculture practices.

Aberrant HPO Axis Alterations and Autoimmune Abnormalities in PCOS Patients with DOR: A Retrospective Analysis.

BACKGROUND: There is a group of polycystic ovary syndrome (PCOS) patients in clinic who have diminished ovarian reserve (DOR) in combination. This study was designed to evaluate the differences in glucolipid metabolism, hypothalamic-pituitary-ovarian (HPO) axis-related parameters, and autoimmune antibodies in PCOS patients with and without DOR. METHODS: A total of 2307 PCOS patients, including 1757 patients with PCOS alone and 550 patients who have both PCOS and DOR, were enrolled in this retrospective study. Parameters of glucolipid metabolism, HPO axis-related parameters, and autoimmune antibodies were measured and analyzed. RESULTS: The prevalence of DOR among all patients with PCOS was 23.84%. Many HPO axis-related parameters, such as follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol (E2), and prolactin (PRL) were significantly different in PCOS with DOR compared with PCOS without DOR. The FSH levels were positively correlated with LH, testosterone (T), and androstenedione (AD) levels, but had no association with glucolipid metabolism after adjusting for body mass index (BMI). Moreover, anti-ovarian antibody (AOAb) and anti-21-OH antibody (21-OHAb) levels were significantly elevated in PCOS patients with DOR. CONCLUSIONS: PCOS patients with DOR showed more chaotic HPO axis hormone levels and elevated autoimmune antibodies, suggesting that autoimmune factors may be the cause of DOR in women with PCOS.

KLF4 transcription factor in tumorigenesis.

Krüppel-like transcriptional factor is important in maintaining cellular functions. Deletion of Krüppel-like transcriptional factor usually causes abnormal embryonic development and even embryonic death. KLF4 is a prominent member of this family, and embryonic deletion of KLF4 leads to alterations in skin permeability and postnatal death. In addition to its important role in embryo development, it also plays a critical role in inflammation and malignancy. It has been investigated that KLF4 has a regulatory role in a variety of cancers, including lung, breast, prostate, colorectal, pancreatic, hepatocellular, ovarian, esophageal, bladder and brain cancer. However, the role of KLF4 in tumorigenesis is complex, which may link to its unique structure with both transcriptional activation and transcriptional repression domains, and to the regulation of its upstream and downstream signaling molecules. In this review, we will summarize the structural and functional aspects of KLF4, with a focus on KLF4 as a clinical biomarker and therapeutic target in different types of tumors.

Effects of virtual reality-based pulmonary rehabilitation in patients with chronic obstructive pulmonary disease: A meta-analysis.

BACKGROUND: Virtual reality (VR)-based pulmonary rehabilitation has been used in the management of chronic obstructive pulmonary disease (COPD). The efficacy of VR-based pulmonary rehabilitation for improving lung function in patients with COPD is controversial. Therefore, the aim of this meta-analysis was to evaluate the efficacy of VR combined with pulmonary rehabilitation for lung function in patients with COPD. METHODS: This study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The search was performed in the Cochrane Library, EMBASE, Web of Science, PubMed, and China National Knowledge Infrastructure databases from inception to February 1, 2023. All included studies were randomized controlled trials that assessed VR combined with pulmonary rehabilitation for COPD patients. The effect size was calculated with standardized mean difference (SMD) and its 95% confidence interval (CI). The Cochrane Collaboration tool was used to assess the risk of bias. Publication bias was assessed by Egger test. RESULTS: A total of 11 studies met the inclusion criteria and were included in this study. The combined effect size showed that VR combined with pulmonary rehabilitation was more effective than pulmonary rehabilitation alone at improving forced expiratory volume in 1 second% (SMD: 0.51; 95% CI 0.19,0.82; P = .002), forced expiratory volume in 1 second/forced vital capacity (SMD: 0.71; 95% CI 0.49,0.93; P < .001), dyspnea (SMD: -0.44; 95% CI -0.66, -0.22; P < .001), and 6-minute walking test (SMD: 059; 95% CI 0.39, 0.79; P < .001). In addition, the VR combined with pulmonary rehabilitation improved depression (SMD: -0.34; 95% CI -0.05, -0.03; P = .033) and anxiety mood (SMD: -0.57; 95% CI -1.11, -0.04; P = .036) compared with the pulmonary rehabilitation group. CONCLUSION: This meta-analysis indicated that VR regimens could be used to enhance the therapeutic effect of pulmonary rehabilitation in patients with COPD. However, as a rapidly evolving field, more well-designed randomized controlled trials are needed to determine the impact of VR-based pulmonary rehabilitation on COPD patients.

Efficacy and safety of Lianhua Qingwen granule in the treatment of non-influenza viral pneumonia: a randomized, double-blind, placebo-controlled, multicenter clinical study.

Objective: To observe the effectiveness and safety of Lianhua Qingwen granule in the treatment of non-influenza viral pneumonia. Methods: This study was a multicenter, randomized, double-blind, placebo-controlled trial. Subjects who met the inclusion and exclusion criteria and were clinically diagnosed with viral pneumonia (negative for influenza virus) were randomly divided into the Lianhua Qingwen granule trial group and placebo control group. Patients in the trial group was given Lianhua Qingwen granule, 2 bags at a time, 3 times a day, and the controls were given placebo, with a treatment course of 7 days. Patients' clinical symptoms and signs, and treatment-associated adverse events were observed. Subjects should be included in the full analysis set (FAS) as long as they were all given the medication and had an effectiveness test performed after randomization. Subjects should be included in the Per Protocol Set (PPS),a subset of the total analysis set, which should contain those with strong compliance, no protocol violations, and complete baseline values for the primary indicators. Results: A total of 169 subjects were enrolled in 12 subcenters, including 151 (76 in the trial group and 75 in the control group) in the FAS and 140 (68 in the trial group and 72 in the control group) in the PPS. After 7 days of treatment, the clinical symptom relief rates were 82.98% (FAS) and 87.12% (PPS) in the trial group, and 75.11% (FAS) and 76.02% (PPS) in the control group, respectively. The clinical symptom relief rates in the trial group were significantly higher than those in the control group (p < 0.001). Significant improvements in single symptoms of cough and expectoration in the trial group were observed compared with the control group (p < 0.05). There were no statistical differences in fever, sputum color change, chest pain, muscle pain, dyspnea, chills, and thirst between the two groups (p > 0.05). Safety: There were no significant differences in body weight, vital signs, blood routine, urine routine, stool routine, and blood biochemical indicators (CK, AST, ALT, Cr, and Bun) between the two groups before and after treatment (p > 0.05). During treatment, there were no significant differences in the incidence of adverse events and serious adverse events between the two groups (p > 0.05). Conclusion: Lianhua Qingwen granules improved the clinical symptoms of patients with non-influenza virus pneumonia, especially ameliorating cough and expectoration. Lianhua Qingwen granules were associated with good safety.

Evolution trend of soil fertility in tobacco-planting area of Chenzhou, Hunan Province, China.

In this study, the data of fertility indicators of soil samples (0-20 cm) in 1980s, 2000 and 2015 in Chenzhou city were used, and the soil integrated fertility index (IFI) was calculated. The results showed that the soil pH was decreased, total nitrogen (TN), organic matter (OM), available phosphorus (AP) and potassium (AK), exchangeable calcium (Ca2+), magnesium (Mg2+) and available copper (Cu) contents were increased, total phosphorus (TP), available sulfur (S) and water-soluble chlorine (Cl-) contents were decreased, total potassium (TK), available boron (B), iron (Fe), manganese (Mn) and zinc (Zn) were decreased first and then increased. In 2015, most of the fields were higher in pH, OM, TN, AN, AK, Ca2+, Mg2+, S, Fe, Mn, Cu and Zn, suitable in B, but lower in TP, AP, TK, available molybdenum (Mo) and Cl-. Most of the fields were in the middle grade of IFI in 2000 and 2015, and the mean IFI increased from 0.492 to 0.556 from 2000 to 2015. Thus, for soil improvement, more attention should be paid to adjust soil pH, reduce the application of organic, nitrogen and calcium fertilizers, while increase the fertilizer application of other nutrients.

Comparative study on electrocardiograms and serological examinations of acute pulmonary embolism and acute non-ST elevation myocardial infarction.

BACKGROUND: The aim of this study was to investigate the value of electrocardiograms (ECGs) and serological examinations in the differential diagnosis of acute pulmonary embolism (APE) and acute non-ST elevation myocardial infarction (NSTEMI) in order to reduce the rate of clinical misdiagnosis. METHODS: The clinical data of 37 patients with APE and 103 patients with NSTEMI admitted to our hospital were retrospectively analyzed. The differences in the clinical manifestations, ECGs, myocardial zymograms, D-dimers, and troponin (cTn) of the two groups were compared. RESULTS: In the patients with APE, the main symptom-found in 25 cases (67.56%)-was dyspnea, while in the patients with NSTEMI, the main symptom-found in 52 cases (50.49%)-was chest tightness. The incidences of sinus tachycardia and SI QIII TIII in the group of patients with APE were higher than in the group of patients with NSTEMI, and the difference was statistically significant (p < .05). There was no statistical significance in the difference of aspartate aminotransferase and lactate dehydrogenase (LDH) in the two groups (p > .05), although there was a statistically significant difference of creatine kinase (CK) and the creatine kinase isoenzyme-MB (CK-MB) in the two groups (p < .05). The levels of D-dimers and cTn were increased in both groups, but the level of D-dimers in the group of patients with APE was higher than that in the group of patients with NSTEMI. CONCLUSION: With the occurrence of clinical manifestations like dyspnea, chest tightness, chest pain, and palpitation of unknown causes, the possibility of APE and NSTEMI should be considered.

The Prognostic Value of the Serum Levels of Brain Natriuretic Peptide, Troponin I, and D-Dimer, in Addition to the Neutrophil-to-Lymphocyte Ratio, for the Disease Evaluation of Patients with Acute Pulmonary Embolism.

OBJECTIVE: The present study aims to investigate whether the serum levels of brain natriuretic peptide (BNP), troponin I (TnI), and D-dimer, in addition to the neutrophil-to-lymphocyte ratio (NLR), can be used to determine the prognosis of patients with acute pulmonary embolism (APE). METHODS: Data were collected from 72 patients that were diagnosed with APE in our hospital from January 2015 to December 2018. These patients were divided into three groups: a high-risk group (n = 10), a moderate-risk group (n = 33), and a low-risk group (n = 29). The serum levels of BNP, TnI, and D-dimer were determined, and the NLR was measured. The receiver operating characteristic (ROC) curve was used to analyze the diagnostic value of the single and combined detection of BNP, TnI, and D-dimer, and the NLR was used to determine the prognosis of patients with APE. RESULTS: The serum levels of BNP, TnI, and D-dimer were significantly higher in the high-risk group than they were in the moderate-risk and low-risk groups (P < 0.05). The serum levels of BNP, TnI, and D-dimer were also significantly higher in the moderate-risk group than they were in the low-risk group (P < 0.05). The serum levels of BNP, TnI, and D-dimer, as well as the NLR, were all significantly higher in the death group than they were in the survival group (P < 0.05). For the combined detection of the four indices, the area under the ROC curve was 0.92, the sensitivity was 0.889, and the specificity was 0.904; each of these values was higher than the corresponding values of single detection. CONCLUSION: In patients with APE, higher serum levels of BNP, TnI, D-dimer and NLR are associated with a higher risk stratification, greater severity of disease, and an increased risk of death.

Metformin inhibits cervical cancer cell proliferation by modulating PI3K/Akt-induced major histocompatibility complex class I-related chain A gene expression.

BACKGROUND: Recent studies have shown that the classic hypoglycemic drug metformin inhibits tumor growth; however, the underlying mechanism remains unclear. We previously showed that metformin disrupts the sponge effect of long non-coding RNA MALAT1/miR-142-3p to inhibit cervical cancer cell proliferation. In this study, we interrogated the ability of metformin to modulate the anti-tumor immune response in cervical cancer. METHODS: The cell counting kit-8 assay was used to detect the viability of cervical cancer cells. Flow cytometry assays were performed to measure cell apoptosis and cell cycle. Lactate dehydrogenase (LDH) cytotoxicity assay was used to detect NK Cell Cytotoxicity. Relative protein levels were determined by immunoblotting and relative gene levels were determined by quantitative real-time PCR. Tumor Xenograft Modeling was used to evaluate the effect of metformin in vivo. RESULTS: Metformin inhibited cervical cancer cell proliferation, cervical cancer xenograft growth, expression of PCNA, p-PI3K and p-Akt. Moreover metformin induced cervical cancer cell apoptosis and caused cancer cell cycle arrest. In addition, metformin upregulated the expression of DDR-1 and p53 in human cervical cancer cells. Furthermore, metformin also regulated the mRNA and protein expression of MICA and HSP70 on the surface of human cervical cancer cells via the PI3K/Akt pathway, enhancing NK cell cytotoxicity. CONCLUSIONS: In conclusion, our results suggest that metformin may be used as immunopotentiator to inhibit cervical cancer progression and may be considered a viable candidate for combination therapy with immunotherapy.

Quantitative proteomics analysis of differentially expressed proteins induced by astragaloside IV in cervical cancer cell invasion.

BACKGROUND: Cervical cancer remains the second leading cause of mortality in women in developing countries. While surgery, chemotherapy, radiotherapy, and vaccine therapy are being applied for its treatment, individually or in combination, the survival rate in advanced cervical cancer patients is still very low. Traditional Chinese medicine has been found to be effective in the treatment of cervical cancer. Astragaloside IV (AS-IV), a compound belonging to Astragalus polysaccharides, shows anticancer activity through several cell signaling pathways. However, the detailed molecular mechanism governing the anticancer activity of AS-IV remains unknown. MATERIAL AND METHODS: In our study, we performed tumor xenograft analysis, transwell cell migration and invasion assay, Western blot analysis, and iTRAQ combination by parallel reaction monitoring (PRM) analysis to study the molecular mechanism of AS-IV in the suppression of cervical cancer cell invasion. RESULTS: Our results showed that AS-IV suppressed cervical cancer cell invasion and induced autophagy in them, with the tumor growth curve increasing slowly. We also identified 32 proteins that were differentially expressed in the SiHa cells when treated with AS-IV, with 16 of them involved in the upregulation and 16 in the downregulation of these cells. These differentially expressed proteins, which were predominantly actin-myosin complexes, controlled cell proliferation and cell development by steroid binding and altering the composition of the cell cytoskeleton. DCP1A and TMSB4X, the two proteins regulating autophagy, increased in cervical cancer cells when treated with AS-IV. CONCLUSIONS: We conclude that AS-IV could inhibit cervical cancer invasion by inducing autophagy in cervical cancer cells. Since iTRAQ combination by PRM has been observed to be useful in identifying macromolecular target compounds, it may be considered as a novel strategy in the screening of anticancer compounds used in the treatment of cervical cancer.

Vorinostat upregulates MICA via the PI3K/Akt pathway to enhance the ability of natural killer cells to kill tumor cells.

Vorinostat has good therapeutic efficacy against primary cutaneous T-cell lymphoma in the refractory stage. However, the molecular mechanism by which it inhibits solid tumors has not been clarified. To investigate the tumor inhibitory mechanism of vorinostat in cervical cancer, this study used Cell Counting Kit-8, flow cytometry, cell invasion and migration assays and the wound healing assay to evaluate the effects of vorinostat on cervical cancer cell proliferation, apoptosis, cell cycle, migration, and invasion. Real-time quantitative PCR and immunoblotting were used to detect gene and protein expression, respectively, of major histocompatibility class I-related chain A, phosphoinositide 3-kinase, phosphorylated PI3K p55 (Tyr199), and p-Akt (Ser473). The lactate dehydrogenase cytotoxicity assay was used to evaluate the ability of natural killer-92 cells to lyse cervical cancer cells. A xenograft nude mouse model was established to analyze the anti-tumor effect of vorinostat in vivo. Our results showed that vorinostat inhibited the proliferation, migration, and invasion of cervical cancer cells. Vorinostat also induced apoptosis and cell-cycle arrest in the S phase, inhibited PI3K (p110α), p-PI3K p55 (Tyr199), and p-Akt (Ser473) protein expression and upregulated MICA expression in vitro and in vivo, and promoted NK-92 cell-mediated cervical cancer cell lysis. The ability of vorinostat to upregulate MICA expression in cervical cancer cells was related to PI3K/Akt signaling. In brief, vorinostat upregulated MICA through the PI3K/Akt pathway and enhanced the sensitivity of cervical cancer cells to the NK cell-mediated cytolytic reaction. The results of this study demonstrate that vorinostat has anti-solid tumor effects on cervical cancer.

iTRAQ-based quantitative proteomic analysis of the inhibition of cervical cancer cell invasion and migration by metformin.

In recent years the anti-diabetic drug metformin has been shown to inhibit tumor growth, but the underlying mechanism is unclear. Our previous results showed that metformin can destroy the sponge effect of long-chain non-coding RNA MALAT1/miR-142-3p and inhibit the proliferation of cervical cancer cells. Metformin can inhibit the PI3K/Akt signaling pathway and synergizes with Nelfinavir to inhibit the proliferation and invasion of cervical cancer cells. In this study, we used iTRAQ-based proteomics, mass spectrometry-based targeted proteomics, immunoblotting, and bioinformatics to analyze the molecular mechanism by which metformin inhibits the proliferation and invasion of cervical cancer cells. We found that 53 proteins were differentially expressed in cervical cancer cells after metformin treatment, of which 20 were up-regulated and 33 were down-regulated. Bioinformatics analysis showed that the 53 differentially expressed proteins are negative regulators of receptor signaling that inhibit cell growth and are mainly enriched in cell growth and apoptosis signaling pathways. We performed PRM verification on 11 of the differentially expressed proteins and found that they were all associated with apoptosis. We also found that metformin up-regulated the expression of the tumor suppressor IGFBP7 to inhibit the proliferation and invasion of cervical cancer cells. Our results indicate that metformin mainly regulates the insulin signaling pathway and interferes with cell proliferation and apoptosis to inhibit proliferation and invasion of cervical cancer cells. These differentially expressed proteins may become new targets for the treatment of cervical cancer.

Evaluation and prognostic value of Cv-aCO2/Da-vO2 in patients with septic shock receiving fluid resuscitation Cv-aCO2/Ca-vO2.

The present study aimed to evaluate the prognostic value of venous-arterial CO2 to arterial-venous O2 (Cv-aCO2/Da-vO2) for patients with septic shock treated by fluid resuscitation. A total of 108 cases who received fluid resuscitation for septic shock at the Intensive Care Unit were retrospectively screened according to the 2012 surviving sepsis campaign guidelines. Patients were divided into 2 groups according to the Cv-aCO2/Da-vO2 ratio at 6 h after fluid resuscitation: Group A, Cv-aCO2/Da-vO2 >1; group B, Cv-aCO2/Da-vO2 ≤1. The resuscitation target rate and transfused resuscitation volume at 6 h exhibited no significant difference between the 2 groups. The cardiac output at 6 and 24 h, as well as the ratio of patients who reached the target of resuscitation within 24 h, the 24-h lactic acid clearance rate and the number of cases with central venous oxygen saturation >70% were significantly decreased in group A compared with those in group B (all P<0.05). The Sequential Organ Failure Assessment score at day 3 in group A was higher compared with that in group B (7.94±1.6 vs. 6.82±1.9; P=0.0013). The mortality rate at day 7 and 35 was higher in group A compared with that in group B (29/52 vs. 6/56, P<0.001; 48/52 vs. 36/56; P<0.001). In conclusion, the Cv-aCO2/Da-vO2 was able to effectively evaluate the success rate of resuscitation and, regarding prognosis, it was able to identify patients at high risk of adverse outcomes.

Efficacy and safety of leflunomide in IgA nephropathy: a systematic review and meta-analysis.

BACKGROUND: The optimal therapy for immunoglobulin A nephropathy (IgAN) remains uncertain. Leflunomide (LEF) is an immunosuppressive drug which may reduce deposition of glomerular autoantibodies and immune complexes. Several clinical trials were designed to evaluate the efficacy of LEF, but their results were controversial. METHODS: Ovid Medline, Embase, the Cochrane Library, PubMed, and CNKI were systematically searched. Search terms included ("glomerulonephritis" OR "nephritis") AND ("immunoglobulin A" OR "IgA") AND "leflunomide". Studies in which patients were diagnosed with IgAN based on renal biopsy were included. Studies needed to report clinical outcomes via either short- or long-term clinical examination, remission rate, or complication rate. RESULTS: Forty-four studies encompassing 1802 patients were included, of which 35 were randomized controlled trials. Results of 24 h post-treatment urine protein tests and serum creatinine tests were significantly lower in patients treat with LEF and corticosteroids (CS) or valsartan (ACEI) (CS + LEF or CS + ACEI) compared with patients treated with CS or ACEI alone (P < 0.05). More patients treated with CS + LEF (31.2%) achieved complete remission (CR) than patients treated with CS alone (22.2%) (RR = 0.71, 95% CI 0.59-0.85, P < 0.05). Although there was no significant difference in CR between patients treated with cyclophosphamide and CS (CS + CTX) and those treated with CS + LEF, the complication rate in the former group was higher (28.4%) than in the latter one (11.4%) (RR = 2.46, 95% CI 1.47-4.13, P < 0.005). CONCLUSION: LEF appears to improve renal function while decreasing loss of urine protein. Combination regimens including LEF were better and safer compared with CS or ACEI alone or combinations including CTX.

Linearly thermal-tunable near-infrared ultra-narrowband metamaterial perfect absorber with low power and a large modulation depth based on a four-nanorod-coupled a-silicon resonator.

The bandwidths of thermal-tunable metamaterial perfect absorbers (MPAs) based on the phase change materials such as Ge2Sb2Te5 and VO2 are usually hundreds of nanometers at near-infrared frequency. Amorphous silicon (a-Si) provides the approach to achieve linearly thermal-tunable ultra-narrowband MPAs, if the absorption band is narrow enough. Four-nanorod-coupled a-Si resonators are proposed in this Letter. An absorption band at 1064 nm is obtained with ultra-narrow bandwidth (FWHM) only 1.4 nm by exciting the coupled magnetic dipole (CMD) mode, which exhibits great linearity to the temperature. In addition, the thermo-optical sensitivity (S=Δλ/ΔT) is about 0.08 nm/°C. The figure of merit of the thermal tunability performance FOM=S/FWHM=0.06. As a modulator, the critical temperature of absorptivity at 1064 nm is only 40°C, which is much lower than the Ge2Sb2Te5 (GST) and VO2. In addition, the modulation depth is up to 82% at near-infrared frequency.

Long noncoding RNA GIHCG functions as an oncogene and serves as a serum diagnostic biomarker for cervical cancer.

Cervical cancer is the most common and lethal gynaecological tumor. Long noncoding RNAs (lncRNAs) have critical roles in various cancers, including cervical cancer. However, few studies investigated the diagnostic value of lncRNAs for cervical cancer. In this study, we investigated the expression pattern of a recently identified lncRNA GIHCG in cervical cancer tissues, cell lines, and serums by qRT-PCR. Furthermore, we explored the roles of GIHCG in cervical cancer using gain-of-function and loss-of-function assays. Our results revealed that GIHCG is up-regulated in cervical cancer tissues and cell lines compared with adjacent normal tissues and normal cervical epithelial cell line, respectively. Furthermore, serum GIHCG is significantly up-regulated in cervical cancer patients compared with healthy controls. ROC curve analysis revealed that serum GIHCG could accurately discriminate cervical cancer patients from healthy controls. Functionally, we found that overexpression of GIHCG promotes cell proliferation, inhibits cell apoptosis, and promotes cell migration of cervical cancer cells. Conversely, depletion of GIHCG inhibits cell proliferation, induces cell apoptosis, and inhibits cell migration of cervical cancer cells. Mechanistically, we found that GIHCG represses the expression of miR-200b. The expression of miR-200b is inversely correlated with the expression of GIHCG in cervical cancer tissues. Moreover, overexpression of miR-200b attenuates the roles of GIHCG in promoting cervical cancer tumor growth in vivo. In summary, this study demonstrated that GIHCG functions as an oncogene in cervical cancer via repressing miR-200b. This study also suggested that GIHCG may be a non-invasive diagnostic biomarker and a potential therapeutic target for cervical cancer.

Metformin combined with nelfinavir induces SIRT3/mROS-dependent autophagy in human cervical cancer cells and xenograft in nude mice.

The molecular mechanisms underlying the antineoplastic properties of metformin combined with nelfinavir remain elusive. To explore this question, transmission electron microscopy (TEM) was used to observe the combinatorial effect of inducing autophagosome formation in human cervical cancer cells. Western blotting respectively assayed protein expression of LC3I, LC3II, Beclin-1, Autophagy-related protein 7 (Atg7), Autophagy-related protein 3 (Atg3), NAD-dependent deacetylase sirtuin-3 (SIRT3) and major histocompatibility complex class I chain-related gene A (MICA). Lactate dehydrogenase (LDH) cytotoxicity assay evaluated natural killer (NK) cell cytotoxicity in the presence of metformin and nelfinavir in combination or each drug alone. Using tumor xenografts in a nude mouse model, antitumor efficacy of the drug combination was assessed. We found that the drug combination could induce autophagosome formation in human cervical cancer cells. The biomarker proteins of autophagy, including Beclin-1, Atg7 and Atg3, decreased, but the ratios of LC3I/II increased. We also found that this drug combination sensitizes human cervical cancer cells to NK cell-mediated lysis by increasing the protein of SIRT3 and MICA. Moreover, this drug combination markedly induced autophagy of SiHa xenografts in nude mice. Therefore, it can be concluded that metformin, in combination with nelfinavir, can induce SIRT3/mROS-dependent autophagy and sensitize NK cell-mediated lysis in human cervical cancer cells and cervical cancer cell xenografts in nude mice. Thus, our findings have revealed the detailed molecular mechanisms underlying the antitumor effects of metformin in combination with nelfinavir in cervical cancer.

Laparoscopic Nerve-Sparing Radical Hysterectomy vs Laparoscopic Radical Hysterectomy in Cervical Cancer: A Systematic Review and Meta-Analysis of Clinical Efficacy and Bladder Dysfunction.

It is widely accepted that nerve-sparing radical hysterectomy is associated with less postoperative morbidity compared with radical hysterectomy, whereas clinical safety is similar in the 2 procedures. However, there is insufficient evidence to compare these procedures performed via a laparoscopic approach. We performed a systematic review and meta-analysis of studies to compare the clinical efficacy and the rate of bladder dysfunction, including urodynamic assessment, in laparoscopic nerve-sparing radical hysterectomy (LNSRH) and laparoscopic radical hysterectomy (LRH). Thirty articles including a total of 2743 participants were analyzed. Operating times were shorter (MD, 29.88 minutes; 95% confidence interval [CI], 11.92-47.83 minutes) and hospital stays were longer (MD, -1.56 days; 95% CI, -2.27 to -0.84 days) in the LRH group compared with the LNSRH group. In addition, blood loss and the number of resected lymph nodes were not significantly different between the 2 groups. However, resected parametrium length (MD, -0.02 cm; 95% CI, -0.05 to -0.00 cm) and vaginal cuff width (MD, -0.06 cm; 95% CI, -0.09 to -0.04) were smaller in the LNSRH group. Furthermore, LNSRH tended to result in more satisfactory micturition (odds ratio, 2.90; 95% CI, 2.01-4.19), shorter catheterization time (MD, -7.20 days; 95% CI, -8.10 to -6.29 days), and shorter recovery to normal postvoid residual urine time (MD, -7.71 days; 95% CI, -8.92 to -6.50 days). Other bladder dysfunction symptoms, including urinary retention, nocturia, dysuria, urinary incontinence, and frequency/urgency were more frequent in the LRH group. Furthermore, LNSRH achieved better results in urodynamic assessments (all p < .05). In conclusion, LNSRH was associated with lower rates of impaired bladder function and a shorter extent of resection compared with LRH. Clinical applications involving LNSRH should be explored with caution.