The Cross-Regulation Between Set1, Clr4, and Lsd1/2 in Schizosaccharomyces pombe.

Eukaryotic chromatin is organized into either silenced heterochromatin or relaxed euchromatin regions, which controls the accessibility of transcriptional machinery and thus regulates gene expression. In fission yeast, Schizosaccharomyces pombe, Set1 is the sole H3K4 methyltransferase and is mainly enriched at the promoters of actively transcribed genes. In contrast, Clr4 methyltransferase initiates H3K9 methylation, which has long been regarded as a hallmark of heterochromatic silencing. Lsd1 and Lsd2 are two highly conserved H3K4 and H3K9 demethylases. As these histone-modifying enzymes perform critical roles in maintaining histone methylation patterns and, consequently, gene expression profiles, cross-regulations among these enzymes are part of the complex regulatory networks. Thus, elucidating the mechanisms that govern their signaling and mutual regulations remains crucial. Here, we demonstrated that C-terminal truncation mutants, lsd1-ΔHMG and lsd2-ΔC, do not compromise the integrity of the Lsd1/2 complex but impair their chromatin-binding capacity at the promoter region of target genomic loci. We identified protein-protein interactions between Lsd1/2 and Raf2 or Swd2, which are the subunits of the Clr4 complex (CLRC) and Set1-associated complex (COMPASS), respectively. We showed that Clr4 and Set1 modulate the protein levels of Lsd1 and Lsd2 in opposite ways through the ubiquitin-proteasome-dependent pathway. During heat stress, the protein levels of Lsd1 and Lsd2 are upregulated in a Set1-dependent manner. The increase in protein levels is crucial for differential gene expression under stress conditions. Together, our results support a cross-regulatory model by which Set1 and Clr4 methyltransferases control the protein levels of Lsd1/2 demethylases to shape the dynamic chromatin landscape.

Immune signatures predict response to house dust mite subcutaneous immunotherapy in patients with allergic rhinitis.

BACKGROUND: Identifying predictive biomarkers for allergen immunotherapy response is crucial for enhancing clinical efficacy. This study aims to identify such biomarkers in patients with allergic rhinitis (AR) undergoing subcutaneous immunotherapy (SCIT) for house dust mite allergy. METHODS: The Tongji (discovery) cohort comprised 72 AR patients who completed 1-year SCIT follow-up. Circulating T and B cell subsets were characterized using multiplexed flow cytometry before SCIT. Serum immunoglobulin levels and combined symptom and medication score (CSMS) were assessed before and after 12-month SCIT. Responders, exhibiting ≥30% CSMS improvement, were identified. The random forest algorithm and logistic regression analysis were used to select biomarkers and establish predictive models for SCIT efficacy in the Tongji cohort, which was validated in another Wisco cohort with 43 AR patients. RESULTS: Positive SCIT response correlated with higher baseline CSMS, allergen-specific IgE (sIgE)/total IgE (tIgE) ratio, and frequencies of Type 2 helper T cells, Type 2 follicular helper T (TFH2) cells, and CD23+ nonswitched memory B (BNSM) and switched memory B (BSM) cells, as well as lower follicular regulatory T (TFR) cell frequency and TFR/TFH2 cell ratio. The random forest algorithm identified sIgE/tIgE ratio, TFR/TFH2 cell ratio, and BNSM frequency as the key biomarkers discriminating responders from nonresponders in the Tongji cohort. Logistic regression analysis confirmed the predictive value of a combination model, including sIgE/tIgE ratio, TFR/TFH2 cell ratio, and CD23+ BSM frequency (AUC = 0.899 in Tongji; validated AUC = 0.893 in Wisco). CONCLUSIONS: A T- and B-cell signature combination efficiently identified SCIT responders before treatment, enabling personalized approaches for AR patients.

Ultrahigh-acetone-sensitivity sensor based on Pt-loaded TiO2porous nanoparticles synthesized via a facile hydrothermal method.

A simple hydrothermal method based on an orthogonal experimental design was used to synthesis Pt-loaded TiO2mesoporous nanoparticles in one step. The successful synthesis of Pt-loaded TiO2nanoparticles was demonstrated by various characterization methods. The effects of the modification of Pt and its explanation are described in detail by means of the test results. Through systematic gas-sensing tests, we found that the Pt-loaded TiO2nanoparticles outperform pure TiO2nanoparticles, with a high response value (S= 42.5) to 200 ppm acetone at 260 °C and with a film thickness of 0.45 mm, far superior to that of pure TiO2. The response time (8 s) and recovery time (11 s) of the material are also relatively good with excellent selectivity and long-term stability (30 days). The frequent use of acetone as an organic solution in factories and laboratories, as well as the possibility of making a preliminary diagnosis of diabetes by detecting acetone levels in exhaled gas, make this work promising for environmental monitoring and medical diagnosis.

Untargeted metabolomic profiling identifies disease-specific and outcome-related signatures in chronic rhinosinusitis.

BACKGROUND: Although metabolomics provides novel insights into disease mechanisms and biomarkers, the metabolic alterations in local tissues affected by chronic rhinosinusitis (CRS) are unknown. OBJECTIVE: This study aimed to determine the metabolomic profiles of sinonasal tissues associated with different types of CRS and their treatment outcomes. METHODS: Untargeted metabolomic profiling was performed on sinonasal tissues obtained from patients with eosinophilic CRS with nasal polyps (CRSwNP), noneosinophilic CRSwNP or CRS without nasal polyps (CRSsNP), and controls. The messenger RNA (mRNA) levels of inflammatory cytokines in nasal tissues were detected by quantitative real-time reverse transcriptase PCR. Nasal polyp tissues were cultured ex vivo and treated with glutathione. RESULTS: Distinct metabolomic profiles were observed for the CRS subtypes. Eosinophilic CRSwNP had profoundly enhanced unsaturated fatty acid oxidization, which correlated with mucosal eosinophil numbers and IL-5 mRNA levels. Noneosinophilic CRSwNP was characterized by uric acid accumulation. Increased uric acid levels were positively correlated with mucosal neutrophil numbers and IFN-γ, IL-17A, IL-1ß, and IL-8 mRNA levels. Disrupted purine metabolism was specifically detected in CRSsNP. Reduced levels of amino acid metabolites were found in eosinophilic CRSwNP and CRSsNP, and were inversely associated with mucosal total inflammatory cell numbers and inflammatory cytokines. Compared to non-difficult-to-treat CRS, difficult-to-treat CRS had higher glutathione disulfide levels, which were positively correlated with IL-8 mRNA levels. Glutathione treatment reduced IL-8 mRNA expression in cultured nasal polyp tissues. CONCLUSIONS: Specific metabolic signatures are associated with different types of CRS, inflammatory patterns, and disease outcomes, which may provide novel insights into pathophysiologic mechanisms, subtype-specific biomarkers, and treatment targets of CRS.

Childbirth Readiness Scale (CRS): instrument development and psychometric properties.

BACKGROUND: Childbirth preparation plays an important role in reducing maternal mortality and improving women's childbirth experience. Evaluating childbirth readiness levels before and after interventions provides a basis for formulating more targeted and effective interventions. However, existing tools only assess partial childbirth preparation or have limited evidence of reliability and validity. The aim of this study was thus to develop a new instrument for use during the third trimester to comprehensively assess the readiness level of pregnant women, and test the scale's psychometric properties. METHODS: The scale was developed through exploratory mixed methods including qualitative and quantitative phases. A literature review and in-depth semi-structured interviews were utilized to identify the scale items. A Delphi expert consultation evaluated the content validity. Psychometric testing was conducted in a convenience sample of 731 pregnant women in the third trimester (recruited from 3 tertiary hospitals in Hubei province in China). Item analysis was used to screen items; exploratory factor analysis was performed to extract factors; confirmatory factor analysis was performed to evaluate fit on the factor structures. RESULTS: The final scale consisted of four dimensions and 18 items that explained 65.8% of the total variance. Confirmative factor analysis (CFA) model showed that the 4-factor model fits the data well. The total Cronbach alpha coefficient of the total scale and 4 factors was 0.935 and 0.853-0.914. The split-half reliability was 0.880. The dimensions comprised "Self-management", "Information literacy", "Birth confidence" and "Birth plan". CONCLUSIONS: The childbirth readiness scale we developed has good reliability and validity, and can be used to comprehensively assess the readiness level of pregnant women. In addition to understanding the overall level of women's childbirth readiness, using subscale scores, improvements can be targeted to specific areas of the preparation for childbirth, to improve the efficiency of the intervention.

The efficacy of Raman spectroscopy in lung cancer diagnosis: the first diagnostic meta-analysis.

In recent years, many researches have explored the diagnostic value of Raman spectroscopy in multiple types of tumors. However, as an emerging clinical examination method, the diagnostic performance of Raman spectroscopy in lung cancer remains unclear. Relevant diagnostic studies published before 1 June 2020 were retrieved from the Cochrane Library, PubMed, EMBASE, China National Knowledge Internet (CNKI), and WanFang databases. After the literature was screened, two authors extracted the data from eligible studies according to the inclusion and exclusion criteria. Obtained data were pooled and analyzed using Stata 16.0, Meta-DiSc 1.4, and RevMan 5.3 software. Fourteen diagnostic studies were eligible for the pooled analysis which includes 779 patients. Total pooled sensitivity and specificity of Raman spectroscopy in diagnosing lung cancer were 0.92 (95% CI 0.87-0.95) and 0.94 (95% CI 0.88-0.97), respectively. The positive likelihood ratio was 15.2 (95% CI 7.5-30.9), the negative likelihood ratio was 0.09 (95% CI 0.05-0.14), and the area under the curve was 0.97 (95 % CI 0.95-0.98). Subgroup analysis suggested that the sensitivity and specificity of RS when analyzing human tissue, serum, and saliva samples were 0.95 (95% CI 0.88-0.98), 0.97 (95% CI 0.89-0.99), 0.88 (95% CI 0.80-0.93), 0.87 (95% CI 0.78-0.92), 0.91 (95% CI 0.80-0.96), and 0.95 (95% CI 0.73-0.99), respectively. No publication bias or threshold effects were detected in this meta-analysis. This initial meta-analysis indicated that Raman spectroscopy is a highly specific and sensitive diagnostic technology for detecting lung cancer. Further investigations are also needed to focus on real-time detection using Raman spectroscopy under bronchoscopy in vivo. Moreover, large-scale diagnostic studies should be conducted to confirm this conclusion.

The feasibility, safety and short-term clinical efficacy of laparoscopic anterior resection of rectal cancer with left colonic artery (LCA) preservation and natural orifice specimen extraction (NOSE).

BACKGROUND: Natural orifice specimen extraction surgery (NOSES) has the advantages of less postoperative pain, fast bowel function recovery, reduced hospital stay and better cosmetic effects. In our centre, anterior resection of rectal cancer with preservation of the left colonic artery (LCA) was performed using NOSES. The feasibility, safety and short-term clinical efficacy of the technique were discussed. METHODS: A retrospective analysis was performed on 19 patients who underwent laparoscopic anterior resection of rectal cancer with left colonic artery preservation and natural orifice specimen extraction in the Gastrointestinal Surgery Center of Sichuan Cancer Hospital from September 2018 to December 2019. General information about the patients, perioperative data and short-term postoperative results were analysed. RESULTS: All operations were completed smoothly, with an average operation duration of 304.36 ± 45.04 min, intraoperative bleeding of 76.31 ± 61.12 ml, first time off bed of 14.42 ± 3.56 h, first time to anus exhaust of 15.26 ± 8.92 h, first time to liquid diet of 2.94 ± 1.12 days, and average postoperative stay of 10.21 ± 3.13 days. Two patients developed temporary intestinal obstruction, and one patient developed pulmonary infection. All of them recovered well after active supportive treatment and were successfully discharged. CONCLUSION: Laparoscopic NOSES for rectal cancer with left colon artery preservation is safe and feasible, with satisfactory short-term results, and is worthy of further clinical investigation.

Epigenetic Modulation of Opioid Receptors by Drugs of Abuse.

Chronic exposure to drugs of abuse produces profound changes in gene expression and neural activity associated with drug-seeking and taking behavior. Dysregulation of opioid receptor gene expression is commonly observed across a variety of abused substances including opioids, cocaine, and alcohol. Early studies in cultured cells showed that the spatial and temporal gene expression of opioid receptors are regulated by epigenetic mechanisms including DNA and histone modifications and non-coding RNAs. Accumulating evidence indicate that drugs of abuse can modulate opioid receptor gene expression by targeting various epigenetic regulatory networks. Based on current cellular and animal models of substance use disorder and clinical evidence, this review summarizes how chronic drug exposure alters the gene expression of mu, delta, kappa, and nociceptin receptors via DNA and histone modifications. The influence of drugs of abuse on epigenetic modulators, such as non-coding RNAs and transcription factors, is also presented. Finally, the therapeutic potential of manipulating epigenetic processes as an avenue to treat substance use disorder is discussed.

Minimally invasive versus conventional fixation of tracer in robot-assisted pedicle screw insertion surgery: a randomized control trial.

BACKGROUND: This study evaluated the minimal invasiveness, safety, and accuracy of robot-assisted pedicle screw placement procedure using a modified tracer fixation device. METHODS: Patients were randomly assigned to conventional fixation group (25 patients) and modified fixation group (27 patients). RESULTS: No baseline statistical difference was observed between the groups (P > 0.05). The length of unnecessary incision, amount of bleeding, and fixation duration for tracer fixation respectively were 6.08 ± 1.02 mm, 1.46 ± 0.84 ml, and 1.56 ± 0.32 min in the modified fixation group and 40.28 ± 8.52 mm, 12.02 ± 2.24 ml, and 5.08 ± 1.06 min in the conventional group. The difference between both groups was significant (P < 0.05). However, no significant difference between the two groups was observed in terms of the accuracy of pedicle screw placement (P > 0.05). CONCLUSIONS: The modified minimally invasive procedure for tracer fixation results in minimal trauma and is simple, reliable, and highly safe. Additionally, the procedure does not compromise the accuracy of pedicle screw placement. Thus, it has great clinical applicable value. TRIAL REGISTRATION: Chinese Clinical Trial Registry: Registration number, ChiCTR1800016680; Registration Date, 15/06/2018.

[Chemical profiling of Artemisia rupestris using HPLC-IT-TOF-MS].

Artemisia rupestris is widely used as a folk medicine of Uygur and Kazak with blood and detoxification, deaccumulation stagnation, clearing heat digestion and other effects. Currently, the chemical profile of A. rupestris has not been disclosed, resulting in a great obstacle for the systematic clarification of the efficacy materials and the quality evaluations. In this paper, HPLC-IT-TOF-MS was deployed to characterize the chemical constituents in A. rupestris. As a result, a total of 124 compounds were detected in 75% ethanol extract of A. rupestris. By comparing with the reference compounds, seven chlorogenic acids, and four flavonoids as well as one sesquiterpenoid were definitely identified. Moreover, twenty sesquiterpenes, sixty-five flavonoids and twenty-three chlorogenic acids were preliminarily identified by matching MS/MS spectral information with literature data and applying those empirical mass spectrometric cracking rules. In current study, the chemical composition of A. rupestris was profiled in depth, and the findings are envisioned to provide a theoretical basis for the further studies of this well-known herbal medicine, such as efficacy material characterization and quality assessment.

The effect of adjuvant chemotherapy in resectable cholangiocarcinoma: A meta-analysis and systematic review.

BACKGROUND: The benefit of adjuvant chemotherapy for resectable cholangiocarcinoma remains unclear due to the lack of randomized control studies. This study aimed to investigate the possible benefit of postoperative adjuvant chemotherapy for resectable cholangiocarcinoma. DATA SOURCES: Relevant research articles published before 1st March 2018 in PubMed, Embase and the Cochrane library databases were retrieved. Published data were extracted and analyzed by RevMan 5.3, and the results were presented as hazard ratios (HRs) [95% confidence intervals (CI)] and forest plots. RESULTS: One prospective and eighteen retrospective studies were included, with a total number of 11,458 patients, 4696 of whom received postoperative chemotherapy. There was a significant improvement of the overall survival (OS) for patients who underwent operation + adjuvant chemotherapy compared to those who underwent operation alone (HR = 0.61; P < 0.001). Subgroup analyses show that the postoperative chemotherapy group compared with operation alone group are indicated as follows: hilar cholangiocarcinoma group (HR = 0.60; P < 0.001), intrahepatic cholangiocarcinoma group (HR = 0.60; P < 0.001), R1 resection group (HR = 0.71; P = 0.04), LN-positive diagnosis group (HR = 0.58; P < 0.001), gemcitabine-based chemotherapy group (HR = 0.42; P < 0.001), distal cholangiocarcinoma group (HR = 0.48; P = 0.17), R0 resection group (HR = 0.69; P = 0.43), and 5-flurouracil-based chemotherapy group (HR = 0.90; P = 0.66), respectively. CONCLUSIONS: Postoperative adjuvant chemotherapy can improve the OS in intrahepatic and hilar cholangiocarcinoma patients. However, distal cholangiocarcinoma patients gain no benefit from postoperative adjuvant chemotherapy. Prospective randomized trials are warranted in order to define the standard chemotherapy regimen.

Prediction of asialoglycoprotein receptors by correlated liver function parameters before hepatectomy.

Flow cytometric analysis of asialoglycoprotein receptor (ASGPR) levels on the surface of hepatocytes, which were obtained from the liver specimens of patients that received hepatectomy, were used as predictors of liver dysfunction after major hepatectomy for primary hepatocellular carcinoma (HCC) in Chinese patients, based on our previous study which confirmed the value of ASGPR levels on the surface of hepatocytes in evaluating the liver reserve function. The current study was planned to establish a conversion formula for the value of ASGPR with correlated liver function parameters. It was conducted from January 1, 2014, to June 30, 2015, at Beijing DiTan Hospital, Beijing, China, and comprised 55 patients having undergone major hepatectomy. The outcomes of hepatectomy were compared with ASGPR levels and preoperative liver function parameters. A multiple linear regression model was used to identify the converted ASGPR value. The calculated ASGPR level was derived as: 80.695 + 0.002 × cholinesterases (CHE) (IU/L) - 0.620 × indocyanine green retention rate at 15 min (ICGR15)(%) - 0.655 × total bilirubin (TB) (umol/L). Receiver-operator characteristic curve analysis showed that the sensitivity and specificity of the ASGPR value <68.18% were 100% and 77.3% respectively for predicting liver dysfunction after hepatectomy. The converted ASGPR value may be reliable index for hepatic functional reserve in patients undergoing hepatectomy.

The power peripherally inserted central catheter is superior to a central venous catheter in management of patients with esophageal variceal bleeding undergoing devascularization.

Peripherally-inserted central catheters (PICC) have a greater retention time and less complications compared to central venous catheters (CVC). The study was conducted from From January of 2014 to December 2015 at Beijing DiTan Hospital, Beijing, China, and comprised 70 patients undergoing devascularisation. Of the total, 36(51.4%) patients underwent placement of PICC (Group A), while 34(48.6%) underwent had CVC (Group B). Venous catheterisation was successful in all patients. The median duration of venous catheterization in Group A was greater than that in Group B (p=0.002). Catheter-associated complications did not differ between the groups (p=0.46). The level of blood platelet (PLT) count, Prothrombin activity (PTA) and white blood cell (WBC) count before venous catheterisation were independent risk factors for bleeding at the puncture site and catheter-related infections. A Power PICC may be a better choice than a CVC in patients undergoing devascularisation requiring catheterisation. For patients with a lower PLT count, a decreased PTA, or a decreased WBC, venous catheterisation should be performed with caution.

Successive and cyclic oral contraceptive pill pretreatment improves IVF/ICSI outcomes of PCOS patients and ameliorates hyperandrogenism and antral follicle excess.

OBJECTIVES: To evaluate different oral contraceptive pill (OCP) pretreatment associated differential in-vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) outcomes of polycystic ovary syndrome (PCOS) patients and explore enhanced hormonal balance induced by the pretreatment. METHODS: This retrospective study included 500 PCOS women and 565 normal ovulating counterparts undergoing IVF/ICSI. The PCOS patients were divided into three groups based on the OCP pretreatment regimens: non-OCP (without OCP pretreatment), unsuccessive OCP (the period of successive pretreatment ≤2 months) and successive OCP (the period of successive pretreatment ≥3 months) groups. Comprehensive hormonal and ultra-sonographic assessments were performed before/after IVF pretreatment. Confounding factors affecting pregnancy outcomes were analyzed with logistic regression. RESULTS: PCOS patients with significant endocrine disorders had reduced implantation and pregnancy rates and increased miscarriage rate. Successive, not unsuccessive OCP pretreatment, significantly improved the implantation and pregnancy rates, and reduced the incidence of monotocous small-for-gestational age infants, which was accompanied by remarkably decreased hyperandrogenism and antral follicles. CONCLUSION: PCOS is an independent risk factor for poor IVF outcome. Successive, not unsuccessive, OCP cyclical pretreatment could improve pregnancy outcome of PCOS patients, associated with reduction of hyperandrogenism and antral follicle excess.

Effect of multistep processing technique on the formation of micro-defects and residual stresses in zirconia dental restorations.

PURPOSE: The clinical failures of zirconia dental restorations are often caused by extrinsic artifacts introduced by processing. The aim of this study was to investigate the micro-defects and residual stresses generated during the multistep process of zirconia dental restorations. MATERIALS AND METHODS: Thermal spray granulated 3Y-TZP powders were dry pressed by two tools exhibiting distinctly different Young's moduli, cold isostatic pressed (CIP-ed), and pressure-less fully sintered. The green bodies pressed by a stiff tool were treated with different procedures: direct milling (green milling) followed by fully sintering; half-sintering and milling (raw milling) with or without fully sintering; and fully sintering followed by grinding. The fully sintered 3Y-TZP crowns were clinically adjusted using both a diamond bur and SiC bur, respectively. Phase composition and microstructure of the pressed, milled, and ground surfaces were studied by XRD and SEM. RESULTS: Tetragonal phase was the main phase of all detected 3Y-TZP specimens. Excessive residual stresses introduced by raw milling and grinding were confirmed by a strained T (111) peak, monoclinic phase, and obviously changed I(002)t /I(200)t ratio. The residual stresses would form a compressive stress layer, while it was too shallow to inhibit crack propagation even for ground specimens. Large voids with high-coordination numbers were the common packing micro-defects. Once formed, they were barely healed by CIP-ing and sintering. A stiff pressing tool was confirmed to be useful for reducing the surface packing voids. Milling removed the surface voids, but was no help for the interior ones. Raw milling introduced more serious chippings, most originating from the existing packing voids, than green milling due to its brittle failure and was less recommended for production. Grinding dense 3Y-TZP caused surface grain refinement and much more severe micro-defects, especially when clinical adjustment was applied by diamond bur compared to SiC bur. CONCLUSIONS: Micro-defects and residual stresses are introduced and accumulated through the entire production chain and determine the final microstructure of zirconia dental restorations. Several procedural improvements are offered and expected to reduce processing micro-defects.

Dysbiosis and interactions of the mycobiome and bacteriome in mucosal lesions of erosive and non-erosive oral lichen planus patients.

Background: Oral lichen planus (OLP) is a common oral mucosal disease, clinically categorized into erosive OLP (EOLP) and non-erosive OLP (NEOLP) based on symptoms, but its pathogenic mechanism remains unclear. This study aims to explore the relationship between OLP and the oral microbiome. Methods: We collected oral mucosal samples from 49 patients and 10 healthy individuals and conducted 16S rRNA and ITS gene sequencing to explore the oral fungal and bacterial communities. Results: We observed significantly lower α diversity of fungi in the EOLP group, with Candida being significantly enriched as the main dominant genus. In the NEOLP group, Aspergillaceae were significantly enriched. The EOLP group showed significant enrichment of Aggregatibacter and Lactobacillus, but the relative abundance of Streptococcus was notably lower than in the other two groups. In the NEOLP group, two species including Prevotella intermedia were significantly enriched. The microbial co-occurrence and co-exclusion networks display distinct characteristics across the three groups, with Lactobacillus assuming a significant bridging role in the ELOP group. Conclusions: Our study indicates that EOLP and NEOLP experience varying degrees of dysbiosis at both the fungal and bacterial levels. Therefore, the pathogenic mechanisms and interactive relationships of these microbiota associated with OLP merit further in-depth investigation.

The microbial community in the oral lesions of EOLP patients exhibits highly distinctive features, both in terms of bacteria and fungi.In NEOLP patients, the overall bacterial composition does not exhibit significant differences compared to the healthy population, but P. intermedia and Aspergillaceae are notably enriched.

Corrigendum: Characterizing the neutrophilic inflammation in chronic rhinosinusitis with nasal polyps.

[This corrects the article DOI: 10.3389/fcell.2021.793073.].

Identification of a mutation in GDF9 as a novel cause of diminished ovarian reserve in young women.

STUDY QUESTION: Do any mutations in growth differentiation factor 9 (GDF9) have a role in diminished ovarian reserve (DOR) in young women? SUMMARY ANSWER: The GDF9 p.R146C mutation may be a source of DOR in some young women. WHAT IS KNOWN ALREADY: DOR affects 10% of women under 37 years of age and is associated with accelerated expenditure of follicles. GDF9 is an oocyte-secreted factor that plays a critical role in follicular development and female fertility. Several GDF9 variants have been linked to ovarian dysfunction. STUDY DESIGN, SIZE, DURATION: This case-control study included 139 women with DOR and 152 controls aged under 37 years. PARTICIPANTS/MATERIALS, SETTING, METHODS: All women were recruited in a Chinese tertiary center and underwent DNA sequencing of GDF9 gene. We then determined the molecular and biological properties of mutant GDF9 proteins using protein expression, structural prediction and functional analyses. MAIN RESULTS AND THE ROLE OF CHANCE: We identified two mutations in the proregion of GDF9 gene: c.169T > G (p.D57Y) and c.436T > C (p.R146C). The p.R146C mutation was found in three women with DOR but was absent in the control population. This mutation was also associated with significant reductions in GDF9 mature protein secretion in cultured cells. Functional studies with human granulosa cells (GCs) showed that the p.R146C mutation reduced the abilities of GDF9 to stimulate GC proliferation and to activate the Smad2 pathway. Protein structure modeling predicted that p.R146C disrupted an α-helix in GDF9 protein. In contrast with p.R146C, the p.D57Y mutation, found in both the DOR and control groups (6 versus 2), had no obvious deleterious effects. LIMITATIONS, REASONS FOR CAUTION: Larger studies in varying populations may validate the role of GDF9 mutation in young women with DOR. WIDER IMPLICATIONS OF THE FINDINGS: These results may provide new insights into the pathophysiological mechanisms of early-onset DOR.

Clinical study of cisplatin hyperthermic intraperitoneal perfusion chemotherapy in combination with docetaxel, 5-flourouracil and leucovorin intravenous chemotherapy for the treatment of advanced-stage gastric carcinoma.

BACKGROUND/AIMS: The purpose of this study is to observe and compare the preliminary efficacy and side effects of docetaxel, 5-fluorouracil and leucovorin intravenous chemotherapy in combination with cisplatin hyperthermic intraperitoneal perfusion chemotherapy for the treatment of advanced gastric cancer. METHODOLOGY: Retrospectively analyzed 101 patients with advanced gastric cancer receiving docetaxel, 5-fluorouracil, leucovorin and cisplatin intravenous chemotherapy or intravenous administration of docetaxel, 5-fluorouracil and leucovorin combined with cisplatin hyperthermic intraperitoneal perfusion chemotherapy, 49 patients in intravenous chemotherapy (VC) group, 52 patients in hyperthermic intraperitoneal perfusion chemotherapy (HIPEC) group. RESULTS: The response rate was 44.9% (22/49) in VC group and 65.4% (34/52) in HIPEC group, among which there was 1 case of CR, and the difference was statistically significant (p= 0.038). For CBR evaluation, the effective rate was 65.3% (32/49) in VC group and 82.7% (43/52) in HIPEC group, and the difference was statistically significant (p= 0.0458). The median progress free survival time (PFS) was 3.4 months in VC group and 4.6 months in HIPEC group, the difference was statistically significant (p= 0.045). The median overall survival time (OS) was 6.7 months in VC group and 7.5 months in HIPEC group, the difference was not statistically significant (p= 0.201). The main side effects in two groups were well tolerated, and there was no statistically significant difference. CONCLUSIONS: The short-term efficacy and PFS of HIPEC plus intravenous chemotherapy were better than single intravenous chemotherapy, and there was no significant improvement in OS, the side effects were similar in two groups with good tolerability.

Clinical application of fiberoptic bronchoscope combined with visual laryngeal mask awake tracheal intubation technique: a case report.

We presented a case of successful awake endotracheal intubation in a patient with a giant goiter and severe tracheal stenosis. The patient had difficulty in airway management during the perioperative anesthesia due to tracheal deviation and stenosis caused by tumor compression. We applied a visual laryngeal mask combined with fiberoptic bronchoscope to visualize the whole procedure of endotracheal intubation, from visually assessing the glottic, subglottic, and the tracheal conditions, to evaluating the pressure of the tumor on the trachea and the maximum tracheal tube diameter that could be passed. During the entire process, the patient remained awake, maintained spontaneous breathing, and actively cooperated with the clinical staff. Hence, we demonstrated that this method is safe, effective, operable, and could be generalized as a form of endotracheal intubation for patients with known difficult airways.