Human tear film protein sampling using soft contact lenses.

BACKGROUND: Human tear protein biomarkers are useful for detecting ocular and systemic diseases. Unfortunately, existing tear film sampling methods (Schirmer strip; SS and microcapillary tube; MCT) have significant drawbacks, such as pain, risk of injury, sampling difficulty, and proteomic disparities between methods. Here, we present an alternative tear protein sampling method using soft contact lenses (SCLs). RESULTS: We optimized the SCL protein sampling in vitro and performed in vivo studies in 6 subjects. Using Etafilcon A SCLs and 4M guanidine-HCl for protein removal, we sampled an average of 60 ± 31 µg of protein per eye. We also performed objective and subjective assessments of all sampling methods. Signs of irritation post-sampling were observed with SS but not with MCT and SCLs. Proteomic analysis by mass spectrometry (MS) revealed that all sampling methods resulted in the detection of abundant tear proteins. However, smaller subsets of unique and shared proteins were identified, particularly for SS and MCT. Additionally, there was no significant intrasubject variation between MCT and SCL sampling. CONCLUSIONS: These experiments demonstrate that SCLs are an accessible tear-sampling method with the potential to surpass current methods in sampling basal tears.

The benefit of omeprazole exposure on all-cause mortality and length of ICU/hospital stay might vary with age in critically ill pediatric patients: A cohort study.

PURPOSE: To investigate the association between proton pump inhibitors (PPIs) administration during hospitalization and mortality and length of stay in critically ill pediatric patients. MATERIALS AND METHODS: This is a retrospective observational cohort study on pediatric ICU patients (0 to 18 years). Propensity score matching (PSM), Kaplan-Meier curves, Cox proportional hazards model and Linear regression model was applied for assessing the effects of PPIs on mortality and other outcomes during hospitalization. RESULTS: A total of 2269 pediatric ICU patients were included, involving 1378 omeprazole (OME) users and 891 non-OME users. The results showed significant association between OME exposure and decreased ICU stay (ß -0.042; 95% CI -0.073--0.011; P = 0.008) but prolonged non-ICU hospital stay (ß 0.121; 95% CI 0.097-0.155; P = 0.040). No statistical significance was observed between OME exposure and reduced mortality, but the OME group had a slightly decreased tendency in 28-day mortality (HR 0.701; 95% CI 0.418-1.176) and in-hospital mortality (HR 0.726; 95% CI 0.419-1.257). Furthermore, subgroup analyses revealed that the decreased tendency of mortality were more obvious in patients less than 1 year old compared with older pediatric patients, although not statistically significant. In addition, we also observed that OME exposure was significantly associated with reduced mortality of general ICU subgroup. CONCLUSIONS: This study provided a sign that PPIs used only in the ICU, rather than throughout hospital stay, might provide more benefit for critically ill pediatric patients. Additionally, younger pediatric patients might gain relatively more benefit than older children when receiving PPIs.

Effective doses of midazolam oral solution for the prevention of preoperative anxiety in paediatric patients.

BACKGROUND: More than 60% children exhibit anxiety before undergoing an anesthetic-surgical procedure, particularly among pre-school paediatric patients. Oral midazolam can provide procedural sedation for children prior to anesthesia. However, extemporaneous solutions of midazolam are usually prepared from injectable drug solutions, leading to inconsistent efficacy due to variable preparation methods. Xiaoerjing® is the first commercially available oral formulation of midazolam for procedural sedation in children in China. Despite the recommended dosage range of 0.25-0.5 mg/kg, its effective dose is still largely unknown. AIM: To determine the 95% effective dose (ED95) of midazolam oral solution (Xiaoerjing®) for alleviating preoperative anxiety in children prior to mask induction of general anesthesia. DESIGN: The study included 61 children between the ages of 1 and 6 years undergoing elective surgery under general anesthesia. The first patient received a single dose of 0.5 mg/kg midazolam oral solution, which was adjusted for subsequent patients using the biased coin design method based on their response to the previous dose. Doses were increased or decreased at the rate of 0.1 mg/kg. An effective response was defined as having a modified Ramsay sedation score ≥3a, separation anxiety score ≤2, and mask acceptance score ≤2 during inhalational anesthesia induction. RESULTS: Fifty-six children were included in the final analysis. Of those, sedation was successful in 50 patients, with a median separation time of 15 (IQR: 25) min. Midazolam oral solution has an ED95 of 0.8254 mg/kg (95% CI: 0.6915-0.8700 mg/kg) for relieving preoperative anxiety in children. No adverse events occurred following drug administration. CONCLUSION: Midazolam oral solution is a safe and effective medication for relieving preoperative anxiety in children. The ED95 of a single oral dose of midazolam oral solution is 0.8254 mg/kg (95% CI: 0.6915-0.8700 mg/kg).

A meta-analysis of associations of IL-10 gene polymorphisms with acute leukemia susceptibility.

BACKGROUND: Recently, increasing evidence has demonstrated that IL-10 single nucleotide polymorphisms (SNPs) are associated with the risk of acute leukemia (AL), but the findings of different articles remain controversial. Thus, we performed a meta-analysis to further investigate the exact roles of IL-10 SNPs in AL susceptibility. METHODS: Six common Chinese and English databases were utilized to retrieve eligible studies. The strength of the association was assessed by calculating odds ratios and 95 % confidence intervals. All analyses were carried out using Review Manager (version 5.3) and STATA (version 15.1). The registered number of this research is CRD42022373362. RESULTS: A total of 6391 participants were enrolled in this research. The results showed that the AG genotype of rs1800896 increased AL risk in the heterozygous codominant model (AG vs. AA, OR = 1.41, 95 % CI = 1.04-1.92, P = 0.03) and overdominant model (AG vs. AA + GG, OR = 1.32, 95 % CI = 1.04-1.70, P = 0.03). In the subgroup analysis, associations between the G allele, GG genotype, AG genotype, AG + GG genotype of rs1800896 and increased AL risk were also observed in the mixed population based on allelic, homozygote codominant, heterozygous codominant, dominant, and overdominant models. Furthermore, an association between the AC genotype of rs1800872 and increased AL risk was observed in the Caucasian population in the overdominant model. However, the rs1800871, rs3024489 and rs3024493 polymorphisms did not affect AL risk. CONCLUSION: IL-10 rs1800896 and rs1800872 affected the susceptibility of AL and therefore may be biomarkers for early screening and risk prediction of AL.

Impact of non-pharmaceutical interventions during COVID-19 on future influenza trends in Mainland China.

BACKGROUND: Influenza is a common illness for its high rates of morbidity and transmission. The implementation of non-pharmaceutical interventions (NPIs) during the COVID-19 pandemic to manage its dissemination could affect the transmission of influenza. METHODS: A retrospective analysis, between 2018 and 2023, was conducted to examine the incidence of influenza virus types A and B among patients in sentinel cities located in North or South China as well as in Wuhan City. For validations, data on the total count of influenza patients from 2018 to 2023 were collected at the Central Hospital of Wuhan, which is not included in the sentinel hospital network. Time series methods were utilized to examine seasonal patterns and to forecast future influenza trends. RESULTS: Northern and southern cities in China had earlier outbreaks during the NPIs period by about 8 weeks compared to the 2018-2019. The implementation of NPIs significantly reduced the influenza-like illness (ILI) rate and infection durations. Influenza B Victoria and H3N2 were the first circulating strains detected after the relaxation of NPIs, followed by H1N1 across mainland China. The SARIMA model predicted synchronized H1N1 outbreak cycles in North and South China, with H3N2 expected to occur in the summer in southern cities and in the winter in northern cities over the next 3 years. The ILI burden is expected to rise in both North and South China over the next 3 years, with higher ILI% levels in southern cities throughout the year, especially in winter, and in northern cities mainly during winter. In Wuhan City and the Central Hospital of Wuhan, influenza levels are projected to peak in the winter of 2024, with 2 smaller peaks expected during the summer of 2023. CONCLUSIONS: In this study, we report the impact of NPIs on future influenza trends in mainland China. We recommend that local governments encourage vaccination during the transition period between summer and winter to mitigate economic losses and mortality associated with influenza.

The ATPase mechanism of myosin 15, the molecular motor mutated in DFNB3 human deafness.

Cochlear hair cells each possess an exquisite bundle of actin-based stereocilia that detect sound. Unconventional myosin 15 (MYO15) traffics and delivers critical molecules required for stereocilia development and thus is essential for building the mechanosensory hair bundle. Mutations in the human MYO15A gene interfere with stereocilia trafficking and cause hereditary hearing loss, DFNB3, but the impact of these mutations is not known, as MYO15 itself is poorly characterized. To learn more, we performed a kinetic study of the ATPase motor domain to characterize its mechanochemical cycle. Using the baculovirus-Sf9 system, we purified a recombinant minimal motor domain (S1) by coexpressing the mouse MYO15 ATPase, essential and regulatory light chains that bind its IQ domains, and UNC45 and HSP90A chaperones required for correct folding of the ATPase. MYO15 purified with either UNC45A or UNC45B coexpression had similar ATPase activities (kcat = ∼ 6 s-1 at 20 °C). Using stopped-flow and quenched-flow transient kinetic analyses, we measured the major rate constants describing the ATPase cycle, including ATP, ADP, and actin binding; hydrolysis; and phosphate release. Actin-attached ADP release was the slowest measured transition (∼12 s-1 at 20 °C), although this did not rate-limit the ATPase cycle. The kinetic analysis shows the MYO15 motor domain has a moderate duty ratio (∼0.5) and weak thermodynamic coupling between ADP and actin binding. These findings are consistent with MYO15 being kinetically adapted for processive motility when oligomerized. Our kinetic characterization enables future studies into how deafness-causing mutations affect MYO15 and disrupt stereocilia trafficking necessary for hearing.

Risk factors associated with radiolucent foreign body inhalation in adults: a 10-year retrospective cohort study.

BACKGROUND: Foreign body aspiration (FBA) is a serious condition with high morbidity and mortality rates. Although chest radiography is generally the first radiologic modality used in diagnosis, a substantial percentage of foreign bodies are radiolucent in adults with diagnosis challenging. METHODS: Retrospective review of adult patients with FBA diagnosed by flexible electronic bronchoscopy from 2012 to 2022 collecting demographics, history, hospital presentation, radiographic, and operative details. Risk factors associated with radiolucent foreign body inhalation in adults were explored using appropriate statistical methods. RESULTS: Between 1 January 2012 and 1 January 2022, 114 adult patients diagnosed with FBA were enrolled. The median age of participants was 65 years (IQR 52-74). Multidetector computed tomography (MDCT) examinations identified 28 cases (25%) showing direct visualization of the foreign body (defined as the radiopaque group) and 86 cases (75%) in the radiolucent group. Multivariable stepwise linear regression analysis showed increased odds of radiolucent foreign body inhalation in adults associated with pneumonic patches in MDCT (OR 6.99; 95% CI 1.80-27.22; P = 0.005) and plants/meat foreign bodies (OR 6.17; 95% CI 1.12-33.96; P = 0.04). A witnessed choking history (OR 0.02; 95% CI 0-0.14; P < 0.001) was a protective factor of radiolucent foreign body inhalation in adults. CONCLUSIONS: Unlike radiopaque FBA, in those presenting with a suspected radiolucent foreign body aspiration, the diagnosis is far more challenging. Risk factors such as lacking a choking history, non-resolving pneumonia (pneumonic patches) in MDCT findings, and plants/meat foreign bodies may help in the early diagnosis of radiolucent foreign body inhalation in adults. Further prospective multicenter studies should be conducted to validate the findings.

Neuraxial analgesia interfered with the circadian rhythm of labor: a propensity score matched cohort study.

OBJECTIVES: To investigate whether neuraxial analgesia and other medical interventions have effects on the circadian rhythm of labor. METHODS: It was a retrospective propensity score matched cohort study. Parturients were recruited, who delivered term singletons in cephalic position, from seven hospitals in Harvard University Partners Healthcare Systems, 2016-2018. The parturients were divided into two groups, neuraxial analgesia delivery and spontaneous vaginal delivery, the stratification was performed according to labor induction, oxytocin, operative delivery. The parturients in each group were divided into 12 periods in every 2 h based on the birth time of babies. Cosine function fitting was used to verify whether the birth time had the characteristic of circadian rhythm. RESULTS: In spontaneous vaginal deliveries, the peak of birth time was at 2:00-4:00, and the nadir was at 14:00-16:00, this showed a circadian rhythm presented by a cosine curve fitting with the formula (y = 0.0847 + 0.01711 × cos(- 0.2138 × x + 0.4471). The labor rhythm of NAD (Neuraxial Analgesia Delivery) group changed completely, inconsistent with the cosine curve fitting of the circadian rhythm. The intervention of induction and oxytocin blurred the circadian rhythm of SVD (Spontaneous Vaginal Delivery) group and increased the amplitude of the fluctuation in NAD (Neuraxial Analgesia Delivery) group. The intervention of operative delivery had changed the distribution curve completely both in the SVD (Spontaneous Vaginal Delivery) group and the NAD (Neuraxial Analgesia Delivery) group. CONCLUSIONS: Neuraxial analgesia did affect on circadian rhythm of labor, changed the cosine rhythm of labor with spontaneous vaginal delivery, and this trend was aggravated by the use of induction, oxytocin and operative delivery.

Construction and validation of a prognostic nomogram for predicting the survival of HIV/AIDS adults who received antiretroviral therapy: a cohort between 2003 and 2019 in Nanjing.

BACKGROUND: Great achievements have been achieved by free antiretroviral therapy (ART). A rapid and accurate prediction of survival in people living with HIV/AIDS (PLHIV) is needed for effective management. We aimed to establish an effective prognostic model to forecast the survival of PLHIV after ART. METHODS: The participants were enrolled from a follow-up cohort over 2003-2019 in Nanjing AIDS Prevention and Control Information System. A nested case-control study was employed with HIV-related death, and a propensity-score matching (PSM) approach was applied in a ratio of 1:4 to allocate the patients. Univariable and multivariable Cox proportional hazards analyses were performed based on the training set to determine the risk factors. The discrimination was qualified using the area under the curve (AUC) and concordance index (C-Index). The nomogram was calibrated using the calibration curve. The clinical benefit of prognostic nomogram was assessed by decision curve analysis (DCA). RESULTS: Predictive factors including CD4 cell count (CD4), body mass index (BMI) and hemoglobin (HB) were determined and incorporated into the nomogram. In the training set, AUC and C-index (95% CI) were 0.831 and 0.798 (0.758, 0.839), respectively. The validation set revealed a good discrimination with an AUC of 0.802 and a C-index (95% CI) of 0.786 (0.681, 0.892). The calibration curve also exhibited a high consistency in the predictive power (especially in the first 3 years after ART initiation) of the nomogram. Moreover, DCA demonstrated that the nomogram was clinically beneficial. CONCLUSION: The nomogram is effective and accurate in forecasting the survival of PLHIV, and beneficial for medical workers in health administration.

Quantitative Analysis Using Consecutive Time Window for Unobtrusive Atrial Fibrillation Detection Based on Ballistocardiogram Signal.

Atrial fibrillation (AF) is the most common clinically significant arrhythmia; therefore, AF detection is crucial. Here, we propose a novel feature extraction method to improve AF detection performance using a ballistocardiogram (BCG), which is a weak vibration signal on the body surface transmitted by the cardiogenic force. In this paper, continuous time windows (CTWs) are added to each BCG segment and recurrence quantification analysis (RQA) features are extracted from each time window. Then, the number of CTWs is discussed and the combined features from multiple time windows are ranked, which finally constitute the CTW-RQA features. As validation, the CTW-RQA features are extracted from 4000 BCG segments of 59 subjects, which are compared with classical time and time-frequency features and up-to-date energy features. The accuracy of the proposed feature is superior, and three types of features are fused to obtain the highest accuracy of 95.63%. To evaluate the importance of the proposed feature, the fusion features are ranked using a chi-square test. CTW-RQA features account for 60% of the first 10 fusion features and 65% of the first 17 fusion features. It follows that the proposed CTW-RQA features effectively supplement the existing BCG features for AF detection.

Statistical Analysis of the Consistency of HRV Analysis Using BCG or Pulse Wave Signals.

Ballistocardiography (BCG) is considered a good alternative to HRV analysis with its non-contact and unobtrusive acquisition characteristics. However, consensus about its validity has not yet been established. In this study, 50 healthy subjects (26.2 ± 5.5 years old, 22 females, 28 males) were invited. Comprehensive statistical analysis, including Coefficients of Variation (CV), Lin's Concordance Correlation Coefficient (LCCC), and Bland-Altman analysis (BA ratio), were utilized to analyze the consistency of BCG and ECG signals in HRV analysis. If the methods gave different answers, the worst case was taken as the result. Measures of consistency such as Mean, SDNN, LF gave good agreement (the absolute value of CV difference < 2%, LCCC > 0.99, BA ratio < 0.1) between J-J (BCG) and R-R intervals (ECG). pNN50 showed moderate agreement (the absolute value of CV difference < 5%, LCCC > 0.95, BA ratio < 0.2), while RMSSD, HF, LF/HF indicated poor agreement (the absolute value of CV difference ≥ 5% or LCCC ≤ 0.95 or BA ratio ≥ 0.2). Additionally, the R-R intervals were compared with P-P intervals extracted from the pulse wave (PW). Except for pNN50, which exhibited poor agreement in this comparison, the performances of the HRV indices estimated from the PW and the BCG signals were similar.

Attention-based multi-scale features fusion for unobtrusive atrial fibrillation detection using ballistocardiogram signal.

BACKGROUND: Atrial fibrillation (AF) represents the most common arrhythmia worldwide, related to increased risk of ischemic stroke or systemic embolism. It is critical to screen and diagnose AF for the benefits of better cardiovascular health in lifetime. The ECG-based AF detection, the gold standard in clinical care, has been restricted by the need to attach electrodes on the body surface. Recently, ballistocardiogram (BCG) has been investigated for AF diagnosis, which is an unobstructive and convenient technique to monitor heart activity in daily life. However, here is a lack of high-dimension representation and deep learning analysis of BCG. METHOD: Therefore, this paper proposes an attention-based multi-scale features fusion method by using BCG signal. The 1-D morphology feature extracted from Bi-LSTM network and 2-D rhythm feature extracted from reconstructed phase space are integrated by means of CNN network to improve the robustness of AF detection. To the best of our knowledge, this is the first study where the phase space trajectory of BCG is conducted. RESULTS: 2000 segments (AF and NAF) of BCG signals were collected from 59 volunteers suffering from paroxysmal AF in this survey. Compared to the classical time and frequency features and the state-of-the-art energy features with the popular machine learning classifiers, AF detection performance of the proposed method is superior, which has 0.947 accuracy, 0.935 specificity, 0.959 sensitivity, and 0.937 precision, for the same BCG dataset. The experimental results show that combined feature could excavate more potential characteristics, and the attention mechanism could enhance the pertinence for AF recognition. CONCLUSIONS: The proposed method can provide an innovative solution to capture the diverse scale descriptions of BCG and explore ways to involve the deep learning method to accurately screen AF in routine life.

Recent Research for Unobtrusive Atrial Fibrillation Detection Methods Based on Cardiac Dynamics Signals: A Survey.

Atrial fibrillation (AF) is the most common cardiac arrhythmia. It tends to cause multiple cardiac conditions, such as cerebral artery blockage, stroke, and heart failure. The morbidity and mortality of AF have been progressively increasing over the past few decades, which has raised widespread concern about unobtrusive AF detection in routine life. The up-to-date non-invasive AF detection methods include electrocardiogram (ECG) signals and cardiac dynamics signals, such as the ballistocardiogram (BCG) signal, the seismocardiogram (SCG) signal and the photoplethysmogram (PPG) signal. Cardiac dynamics signals can be collected by cushions, mattresses, fabrics, or even cameras, which is more suitable for long-term monitoring. Therefore, methods for AF detection by cardiac dynamics signals bring about extensive attention for recent research. This paper reviews the current unobtrusive AF detection methods based on the three cardiac dynamics signals, summarized as data acquisition and preprocessing, feature extraction and selection, classification and diagnosis. In addition, the drawbacks and limitations of the existing methods are analyzed, and the challenges in future work are discussed.

LncRNA GAS5 suppresses proliferation, migration, invasion, and epithelial-mesenchymal transition in oral squamous cell carcinoma by regulating the miR-21/PTEN axis.

Growth-arrest-specific transcript 5 (GAS5) functions as a tumor suppressor in a variety of cancers. GAS5 has been reported to be down-regulated in oral squamous cell carcinoma (OSCC). The aim of this study was to investigate the mechanisms of how GAS5 acts as a tumor suppressor in OSCC. qRT-PCR, cell viability, wound-healing, and transwell assays showed that knockdown of GAS5 increased miR-21 expression and promoted proliferation, migration, invasion, and epithelial-mesenchymal transition of OSCC cells. In contrast, overexpression of GAS5 showed the opposite effects. Furthermore, miR-21 overexpression reversed the effect of GAS5. Western blot showed that knockdown of GAS5 suppressed PTEN, while phosphorylation of Akt was promoted. PCNA, cyclinD1, and Ki-67 were up-regulated, indicating enhanced proliferation. E-cadherin was down-regulated, while N-cadherin, vimentin, and snail1 were increased, indicating augmented epithelial-mesenchymal transition. Overexpression of GAS5 regulated these proteins inversely. Overexpression of miR-21 reversed the effect of GAS5 on these proteins. Taken together, GAS5 suppresses proliferation, migration, invasion, and epithelial-mesenchymal transition in OSCC through the miR-21/PTEN axis and might be a novel therapeutic target for OSCC.

Transcriptome analysis reveals candidate genes related to phosphorus starvation tolerance in sorghum.

BACKGROUND: Phosphorus (P) deficiency in soil is a worldwide issue and a major constraint on the production of sorghum, which is an important staple food, forage and energy crop. The depletion of P reserves and the increasing price of P fertilizer make fertilizer application impractical, especially in developing countries. Therefore, identifying sorghum accessions with low-P tolerance and understanding the underlying molecular basis for this tolerance will facilitate the breeding of P-efficient plants, thereby resolving the P crisis in sorghum farming. However, knowledge in these areas is very limited. RESULTS: The 29 sorghum accessions used in this study demonstrated great variability in their tolerance to low-P stress. The internal P content in the shoot was correlated with P tolerance. A low-P-tolerant accession and a low-P-sensitive accession were chosen for RNA-seq analysis to identify potential underlying molecular mechanisms. A total of 2089 candidate genes related to P starvation tolerance were revealed and found to be enriched in 11 pathways. Gene Ontology (GO) enrichment analyses showed that the candidate genes were associated with oxidoreductase activity. In addition, further study showed that malate affected the length of the primary root and the number of tips in sorghum suffering from low-P stress. CONCLUSIONS: Our results show that acquisition of P from soil contributes to low-P tolerance in different sorghum accessions; however, the underlying molecular mechanism is complicated. Plant hormone (including auxin, ethylene, jasmonic acid, salicylic acid and abscisic acid) signal transduction related genes and many transcriptional factors were found to be involved in low-P tolerance in sorghum. The identified accessions will be useful for breeding new sorghum varieties with enhanced P starvation tolerance.

[A clinical analysis of children with invasive pulmonary fungal infections after biliary atresia surgery].

OBJECTIVE: To investigate the clinical features of invasive pulmonary fungal infections (IPFIs) after biliary atresia (BA) surgery and related risk factors. METHODS: A retrospective analysis was performed for the clinical data of 49 children with IPFIs after BA surgery, including clinical features, lung imaging findings, and pathogenic features. The risk factors for IPFIs after BA surgery were also analyzed. RESULTS: The most common pathogens of IPFIs after BA surgery was Candida albicans (17 strains, 45%), followed by Candida tropicalis (7 strains, 18%), Aspergillus (6 strains, 16%), Candida krusei (3 strains, 8%), Candida glabrata (3 strains, 8%), and Candida parapsilosis (2 strains, 5%). Major clinical manifestations included pyrexia, cough, and shortness of breath, as well as dyspnea in severe cases; the incidence rate of shortness of breath reached 78%, and 35% of all children had no obvious rale. The multivariate logistic regression analysis showed that age at the time of surgery, time of glucocorticoid application, cumulative time of the application of broad-spectrum antibiotics, and recurrent cholangitis were major risk factors for IPFIs after BA surgery. CONCLUSIONS: The three most common pathogens of IPFIs after BA surgery are Candida albicans, Candida tropicalis, and Aspergillus. It is important to perform surgery as early as possible, avoid recurrent cholangitis, and shorten the course of the treatment with broad-spectrum antibiotics and glucocorticoids for decreasing the risk of IPFIs.

Drosophila FMRP participates in the DNA damage response by regulating G2/M cell cycle checkpoint and apoptosis.

Fragile X syndrome, the most common form of inherited mental retardation, is caused by the loss of the fragile X mental retardation protein (FMRP). FMRP is a ubiquitously expressed, multi-domain RNA-binding protein, but its in vivo function remains poorly understood. Recent studies have shown that FMRP participates in cell cycle control during development. Here, we used Drosophila mutants to test if FMRP plays a role in DNA damage response under genotoxic stress. We found significantly fewer dfmr1 mutants survived to adulthood than wild-types following irradiation or exposure to chemical mutagens, demonstrating that the loss of drosophila FMRP (dFMRP) results in hypersensitivity to genotoxic stress. Genotoxic stress significantly reduced mitotic cells in wild-type brains, indicating the activation of a DNA damage-induced G2/M checkpoint, while mitosis was only moderately suppressed in dfmr1 mutants. Elevated expression of cyclin B, a protein critical for the G2 to M transition, was observed in the larval brains of dfmr1 mutants. CycB mRNA transcripts were enriched in the dFMRP-containing complex, suggesting that dFMRP regulates DNA damage-induced G2/M checkpoint by repressing CycB mRNA translation. Reducing CycB dose by half in dfmr1 mutants rescued the defective G2/M checkpoint and reversed hypersensitivity to genotoxic stress. In addition, dfmr1 mutants exhibited more DNA breaks and elevated p53-dependent apoptosis following irradiation. Moreover, a loss-of-heterozygosity assay showed decreased irradiation-induced genome stability in dfmr1 mutants. Thus, dFMRP maintains genome stability under genotoxic stress and regulates the G2/M DNA damage checkpoint by suppressing CycB expression.

MiR-222 targeted PUMA to improve sensitization of UM1 cells to cisplatin.

microRNAs have been shown to play critical roles in regulating the chemosensitivity of cancer cells. As a member of the oncogenic miRNAs (oncomiRs), miR-222 has been reported to drive the oncogenesis of many types of malignancies. However, little is known concerning the specific role of miR-222 in human oral squamous cell carcinoma (OSCC). The present study explored the role and mechanism of miR-222 in increasing the expression of p53 up-regulated modulator of apoptosis (PUMA) and enhancing the sensitivity of OSCC to cisplatin (CDDP). Results showed that antisense (As)-miR-222 inhibits the expression of miR-222. In contrast, PUMA was dramaticallyup-regulated. IC50 values were significantly decreased in cells treated with As-miR-222 combined with CDDP, to a greater extent than in cells treated with CDDP alone. Furthermore, As-miR-222 enhanced apoptosis and inhibited the invasiveness of UM1 cells. Analysis of the above data suggested that, in UM1 cells, there might be a regulatory loop between miR-222 and PUMA, and that miR-222 inhibition increased the chemosensitivity to CDDP. These findings demonstrated that down-regulation of miR-222 could enhance the chemosensitivity of human OSCC cells to CDDP, and that the combination of As-miR-222 and CDDP could be an effective therapeutic strategy by boosting the expression of PUMA for controlling the growth of OSCC.

[Kuntai capsule combined with gonadotropin releasing hormone agonist in treatment of moderate-severe endometriosis: a clinical observation].

OBJECTIVE: To observe the effect of Kuntai Capsule (KC), a Chinese patent medicine, in add-back therapy for gonadotropin-releasing hormone agonist (GnRH-a) treatment for moderate-severe endometriosis (EM). METHODS: Totally 100 patients suffering from stage III/IV EM, who were confirmed by laparoscopic surgery were randomly assigned to the GnRH-a group (A) and the KC combined GnRH-a group (B), 50 in each group. Patients in Group A were hypodermically injected with goserelin (3.6 mg), once per 4 weeks. Those in Group B additionally took KC, 4 pills each time, three times per day. The therapeutic course for all was 12 weeks. Serum levels of estradiol (E2), follicle stimulating hormone (FSH), bone gamma-carboxyglutamic-acid-containing proteins (BGP) were measured respectively. Kupperman Menopausal Index (KMI) and bone mineral density (BMD) of the lumbar vertebra were also compared between the two groups. RESULTS: Serum levels of E2 and FSH both significantly decreased in the two groups at week 12 of the treatment (P < 0.05), when compared with pre-treatment. Compared with before treatment in the same group, KMI increased in the two groups (P < 0.05). Compared with before treatment in the same group, BMI decreased in the two groups with no statistical difference (P > 0.05). Serum BGP increased after 12-week treatment (P < 0.05). Compared with Group A after treatment, serum levels of E2 and FSH both significantly increased in Group B (P < 0.05). There was no statistical difference in KMI between the two groups (P > 0.05). As for the incidence of menopausal symptoms, better effects in improving symptoms such as hot flashes, sleep disorders, and vaginal dryness were obtained in Group B than in Group A (P < 0.05). There was no significant difference in the post-pre-treatment difference of BMI between the two groups, but with statistical post-pre-treatment difference in the BGP level (P < 0.05). CONCLUSIONS: HKC combined GnRH-a could effectively reduce GnRH-a treatment induced partial low estrogen symptoms, improve increased serum BGP levels after GnRH-a therapy.