A binary pulsar in a 53-minute orbit.

Spider pulsars are neutron stars that have a companion star in a close orbit. The companion star sheds material to the neutron star, spinning it up to millisecond rotation periods, while the orbit shortens to hours. The companion is eventually ablated and destroyed by the pulsar wind and radiation1,2. Spider pulsars are key for studying the evolutionary link between accreting X-ray pulsars and isolated millisecond pulsars, pulsar irradiation effects and the birth of massive neutron stars3-6. Black widow pulsars in extremely compact orbits (as short as 62 minutes7) have companions with masses much smaller than 0.1 M⊙. They may have evolved from redback pulsars with companion masses of about 0.1-0.4 M⊙ and orbital periods of less than 1 day8. If this is true, then there should be a population of millisecond pulsars with moderate-mass companions and very short orbital periods9, but, hitherto, no such system was known. Here we report radio observations of the binary millisecond pulsar PSR J1953+1844 (M71E) that show it to have an orbital period of 53.3 minutes and a companion with a mass of around 0.07 M⊙. It is a faint X-ray source and located 2.5 arcminutes from the centre of the globular cluster M71.

A bimodal burst energy distribution of a repeating fast radio burst source.

The event rate, energy distribution and time-domain behaviour of repeating fast radio bursts (FRBs) contain essential information regarding their physical nature and central engine, which are as yet unknown1,2. As the first precisely localized source, FRB 121102 (refs. 3-5) has been extensively observed and shows non-Poisson clustering of bursts over time and a power-law energy distribution6-8. However, the extent of the energy distribution towards the fainter end was not known. Here we report the detection of 1,652 independent bursts with a peak burst rate of 122 h-1, in 59.5 hours spanning 47 days. A peak in the isotropic equivalent energy distribution is found to be approximately 4.8 × 1037 erg at 1.25 GHz, below which the detection of bursts is suppressed. The burst energy distribution is bimodal, and well characterized by a combination of a log-normal function and a generalized Cauchy function. The large number of bursts in hour-long spans allows sensitive periodicity searches between 1 ms and 1,000 s. The non-detection of any periodicity or quasi-periodicity poses challenges for models involving a single rotating compact object. The high burst rate also implies that FRBs must be generated with a high radiative efficiency, disfavouring emission mechanisms with large energy requirements or contrived triggering conditions.

Changes in brain susceptibility in Wilson's disease patients: a quantitative susceptibility mapping study.

AIM: To assess changes in the susceptibility of the caudate nucleus (CN), putamen, and globus pallidus (GP) in patients with neurological and hepatic Wilson's disease (WD) by quantitative susceptibility mapping (QSM). MATERIAL AND METHODS: The brain MRI images of 33 patients diagnosed with WD and 20 age-matched controls were analysed retrospectively. All participants underwent brain T1-weighted, T2-weighted, and QSM imaging using a 1.5 T magnetic resonance imaging (MRI) machine. QSM maps were evaluated with the STISuite toolbox. The quantitative susceptibility levels of the CN, putamen, and GP were analysed using region of interest analysis on QSM maps. Differences among neurological WD patients, hepatic patients, and controls were determined. RESULTS: Susceptibility levels were significantly higher for all examined structures (CN, putamen and GP) in patients with neurological WD compared with controls (all p<0.05) and hepatic WD patients (all p<0.05). No statistically significant differences were found in susceptibility levels between patients with hepatic WD and controls (all p>0.05). CONCLUSION: The QSM technique is a valuable tool for detecting changes in brain susceptibility in WD patients, indicating abnormal metal deposition. Notably, the current findings suggest that neurological WD patients exhibit more severe susceptibility changes compared with hepatic WD patients. Therefore, QSM can be utilised as a complementary method to detect brain injury in WD patients.

Average and statistical properties of coherent radiation from steady-state microbunching.

A promising accelerator light source mechanism called steady-state microbunching (SSMB) is being actively studied. With the combination of strong coherent radiation from microbunching and high repetition rate of a storage ring, high-average-power narrow-band radiation can be anticipated from an SSMB storage ring, with wavelengths ranging from THz to soft X-ray. Such a novel light source could provide new opportunities for accelerator photon science like high-resolution angle-resolved photoemission spectroscopy and industrial applications like extreme ultraviolet (EUV) lithography. In this paper, a theoretical and numerical study of the average and statistical properties of coherent radiation from SSMB are presented. The results show that 1 kW average-power quasi-continuous-wave EUV radiation can be obtained from an SSMB ring provided that an average current of 1 A and a microbunch train with bunch length of 3 nm can be formed at the radiator which is assumed to be an undulator. Together with the narrow-band feature, the EUV photon flux can reach 6 × 1015 photons s-1 within a 0.1 meV energy bandwidth, which is three orders of magnitude higher than that in a conventional synchrotron source and is appealing for fundamental condensed matter physics and other research. In this theoretical investigation, we have generalized the definition and derivation of the transverse form factor of an electron beam which can quantify the impact of its transverse size on coherent radiation. In particular, it has been shown that the narrow-band feature of SSMB radiation is strongly correlated with the finite transverse electron beam size. Considering the pointlike nature of electrons and quantum nature of radiation, the coherent radiation fluctuates from microbunch to microbunch, or for a single microbunch from turn to turn. Some important results concerning the statistical properties of SSMB radiation are presented, with a brief discussion on its potential applications, for example the beam diagnostics. The presented work is of value for the development of SSMB to better serve potential synchrotron radiation users. In addition, this also sheds light on understanding the radiation characteristics of free-electron lasers, coherent harmonic generation, etc.

[Analysis of safety and factors influencing the surgical efficacy of benign biliary stenosis treated with autologous gastric flap repair with the vascular tip].

Objective: To investigate the complication rate and risk factors associated with using autologous gastric flap tissue with a vascular tip to treat benign biliary strictures. Methods: A retrospective analysis was conducted on clinical data of 92 patients with benign biliary stenosis who applied autologous gastric flap tissue to repair the stenosis at the PLA General Hospital from January 2006 to May 2022. Among them, there were 40 males and 52 females, aged from 25 to 79 (50.5±12.9) years. The perioperative clinical data of the patients were recorded(Body Mass Index、preoperative platelets et.), and a multivariate logistic regression model was used to analyze the factors influencing postoperative complications. Long-term follow-up was conducted to evaluate the long-term efficacy of autologous gastric flap tissue with vascular tissues for benign biliary stenosis surgery. Results: The incidence of recent postoperative complications in patients was 26.1%, and univariate analysis showed that preoperative bile-intestinal anastomosis, positive intraoperative bile bacterial culture, low preoperative hemoglobin, and low preoperative platelet count were significantly associated with the occurrence of postoperative complications after biliary stenosis repair with a vascularized gastric flap (P<0.05). Multifactorial analysis showed that low preoperative platelets (OR=0.990, 95%CI: 0.982-0.998, P=0.015), low preoperative hemoglobin (OR=4.953, 95%CI: 1.405-15.010, P=0.012) and positive intraoperative bile bacterial culture (OR=19.338, 95%CI: 3.618-103.360, P<0.001) were independent risk factors for the development of postoperative complications. The excellent long-term follow-up rate of patients was 92.0%. Conclusions: The procedure of repairing benign biliary stenosis with a vascularized gastric flap preserves the function of the sphincter of Oddi and reconstructs the normal physiological passage of the bile duct. This procedure is safe and feasible and provides a reliable option for the surgical treatment of bile duct injury and bile duct stenosis.

[Corneal melt after intracorneal ring segment implantations: a case report].

A 50-year-old female patient presented to the Beijing Tongren Eye Center, Beijing Tongren Hospital, Capital Medical University, Beijing Institute of Ophthalmology, with complaints of right eye pain, tearing, and difficulty opening the eye for over a month after intrastromal corneal ring segment (ICRS) implantation 18 years prior in both eyes. Slit lamp examination revealed corneal stromal melting around the ICRS at the 3 to 4 o'clock position of the right eye, with fluorescein staining. Optical coherence tomography showed epithelial and superficial stromal layer defects in the area of the lesion. The patient was diagnosed with corneal melting after ICRS implantation in the right eye. Under general anesthesia, the corneal stromal ring was removed, and deep lamellar keratoplasty was performed. The patient had no discomfort and the corneal graft remained transparent after the surgery.

[Analysis of long-term outcomes of penetrating keratoplasty for congenital corneal opacity].

Objective: To investigate the long-term outcomes of corneal grafts after penetrating keratoplasty(PK) for congenital corneal opacity(CCO) in children aged 0 to 5 years and the related influencing factors. Methods: It was a retrospective series case study. Data of 39 children (55 eyes) who underwent PK surgery due to CCO in the keratology Department of Beijing Tongren Hospital from April 2014 to April 2018 and were followed up for more than 30 months were collected. Among them, there were 17 males (43.6%) and 22 females (56.4%). The age at operation was (16.2±13.3) months, and the follow-up time was (46.4±13.8) months. Clinical data such as basic information, preoperative diagnosis, operation age, operation method and postoperative complications were recorded. The corneal graft transparency was analyzed according to preoperative diagnosis, corneal neovascularization area, age at surgery, monocular or binocular surgery interval, primary surgery type and further surgery, and postoperative complications were observed. Results: At 12 months, 24 months and the last follow-up after PK, 78.2% (43/55), 70.9% (39/55) and 58.2% (32/55) of the affected eyes had clear corneal grafts, respectively.There was no statistical significance between Peters anomaly and sclerocornea (P>0.05), while the extent of neovascularization in the limbus had a significant effect on corneal graft transparency, and graft opacity was more likely to occur in patients with vessel area exceeding 2 quadrants (P<0.05).The highest corneal graft transparency was found in children aged 1 to 3 years 80.8%(21/26) (P<0.05), followed by children younger than 6 months (7/15).The translucency rate of the corneal graft was higher in patients undergoing unilateral surgery than in those undergoing bilateral surgery (P<0.05).Translucency of corneal graft was higher in children with simple surgery than with combined surgery (P<0.05), however, cataract surgery after PK had no significant effect on corneal graft transparency (P>0.05).The postoperative complications mainly included immune rejection in 19 eyes (34.5%), complicated cataract in 13 eyes (23.6%), glaucoma in 7 eyes (13.2%), persistent corneal epithelial defect in 7 eyes (13.2%). Conclusions: After PK in children with CCO, the transparent rate of corneal grafts decreases gradually with time, but the long-term translucency of corneal grafts can still be obtained. The range of corneal neovascularization, age at the time of surgery, whether the surgery was binocular and whether the surgery was combined had an effect on the transparency of corneal graft.

Construction of miRNA-mRNA network in the differentiation of chicken preadipocytes.

1. MicroRNAs (miRNAs) play key roles in regulating lipid metabolism, adipogenesis and fat deposition in chicken. To date, there are only a few miRNAs that have been confirmed to be involved in chicken adipogenesis. The detailed mechanisms by which miRNAs regulate chicken adipogenesis remain largely unknown.2. To identify candidate miRNAs involved in chicken preadipocyte differentiation and explore potential mechanisms behind their functions, the following study analysed and identified miRNA and mRNA expression levels in undifferentiated and differentiated preadipocytes. Hub miRNA-mRNA interactions were identified, and the degree of connectivity of DE miRNAs in the network was established.3. A total of 145 DE miRNAs and 660 DE mRNAs were identified between undifferentiated and differentiated preadipocytes. An miRNA-mRNA network was constructed, including 29 DE miRNAs and 155 DE mRNAs, forming 470 miRNA-mRNA interactions. Functional enrichment analysis showed that DE mRNAs in the network were significantly enriched in 712 biological processes and 13 KEGG pathways. Based on the connectivity degree, five DE miRNAs with higher degrees miR-195-x, gga-miR-200a-3p, gga-miR-135a-5p, novel-m0067-5p and novel-m0270-5p were identified as hub miRNAs. Fifty-eight DE mRNAs interacted with these five hub miRNAs and formed 70 miRNA-mRNA interactions.4. This study constructed a miRNA-mRNA network associated with chicken preadipocyte differentiation and identified five hub miRNAs in the network. The findings identified a number of chicken adipogenic miRNAs and laid the foundation for elucidating the miRNA-mediated regulatory mechanism in chicken adipogenesis.

The potential effect of microbiota in predicting the freshness of chilled chicken.

1. The goals of this study were to analyse the changes in microbiota composition of chilled chicken during storage and identify microbial biomarkers related to meat freshness.2. The study used 16S rDNA sequencing to track the microbiota shift in chilled chicken during storage. Associations between microbiota composition and storage time were analysed and microbial biomarkers were identified.3. The results showed that microbial diversity of chilled chicken decreased with the storage time. A total of 27 and 24 microbial biomarkers were identified by using orthogonal partial least squares (OPLS) and the random forest regression approach, respectively. The receiver operating characteristic (ROC) curve analysis indicated that the OPLS regression approach had better performance in identifying freshness-related biomarkers. The multiple stepwise regression analysis identified four key microbial biomarkers, including Streptococcus, Carnobacterium, Serratia and Photobacterium genera and constructed a predictive model.4. The study provided microbial biomarkers and a model related to the freshness of chilled chicken. These findings provide a basis for developing detection methods of the freshness of chilled chicken.

[Clinical trials on intrathecal pemetrexed treated leptomeningeal metastases from solid tumors].

Objective: To investigate the feasibility, safety and efficacy of intrathecal pemetrexed (IP) treated for patients with leptomeningeal metastases (LM) from solid tumors. Methods: Forty-seven patients receiving pemetrexed intrathecal chemotherapy in the First Hospital of Jilin University from 2017 to 2018 were selected. The study of pemetrexed intrathecal chemotherapy adopted the classical dose-climbing model and included 13 patients with meningeal metastasis of non-small cell lung cancer who had relapsed and refractory after multiple previous treatments including intrathecal chemotherapy. Based on the dose climbing study, 34 patients with meningeal metastasis of solid tumor who did not receive intrathecal chemotherapy were enrolled in a clinical study using pemetrexed as the first-line intrathecal chemotherapy combined with radiotherapy. Kaplan-Meier method and Log rank test were used for survival analysis, and Cox regression model was used for influencing factor analysis. Results: The dose climbing study showed that the maximum tolerated dose of pemetrexed intrathecal chemotherapy was 10 mg per single dose, and the recommended dosing regimen was 10 mg once or twice a week. The incidence of adverse reactions was 10 cases, including hematological adverse reactions (7 cases), transaminase elevation (2 cases), nerve root reactions (5 cases), fatigue and weight loss (1 case). The incidence of serious adverse reactions was 4, including grade 4-5 poor hematology (2 cases), grade 4 nerve root irritation (2 cases), and grade 4 elevated aminotransferase (1 case). In the dose climbing study, 4 patients were effectively treated and 7 were disease controlled. The survival time was ranged from 0.3 to 14.0 months and a median survival time was 3.8 months. The clinical study of pemetrexed intrathecal chemotherapy combined with radiotherapy showed that the treatment mode of 10 mg pemetrexed intrathecal chemotherapy once a week combined with synchronous involved area radiotherapy 40 Gy/4 weeks had a high safety and reactivity. The incidence of major adverse reactions was 52.9% (18/34), including hematologic adverse reactions (13 cases), transaminase elevation (10 cases), and nerve root reactions (4 cases). In study 2, the response rate was 67.6% (23/34), the disease control rate was 73.5% (25/34), the overall survival time was ranged from 0.3 to 16.6 months, the median survival time was 5.5 months, and the 1-year survival rate was 21.6%. Clinical response, improvement of neurological dysfunction, completion of concurrent therapy and subsequent systemic therapy were associated with the overall survival (all P<0.05). Conclusions: Pemetrexed is suitable for the intrathecal chemotherapy with a high safety and efficacy. The recommended administration regimen was IP at 10 mg on the schedule of once or twice per week. Hematological toxicity is the main factor affecting the implementation of IP. Vitamin supplement can effectively control the occurrence of hematological toxicity.

[The 494th case: acute pancreatitis, acute acalculous cholecystitis and anaphylaxis].

A young male patient with abdominal pain and fever was diagnosed as acute hyper-triglyceridemicpancreatitis is clear. During the recovery of pancreatitis, the patient developed acute acalculous cholecystitis, as well as carbapenem-resistant Enterobacter infection and Cytomegaloviremia, and had anaphylaxis for several times after the use of antibiotics, which cannot be completely explained by drug allergy. This paper analyzes the possible causes of multiple diseases in the same patient in detail.

[Progress on the diagnosis and therapy about atopic diseases and primary immunodeficiency diseases].

Primary immunodeficiency diseases (PID) is a congenital disease caused by single gene germline mutation related to the immune system. PID patients have immune dysregulation, and are susceptible to infectious diseases, autoimmune diseases, autoimmune diseases, allergic diseases, and malignant tumors. The first symptom of some PID patients is atopic disease, therefore they go to the department of allergy, department of pediatrics and other relevant departments. How to identify and diagnose PID in allergic patients, to reduce diagnosis delay and prevent disease aggravation are the abilities that allergists, pediatricians, and doctors in other relevant departments need to master. This article summarizes the warning signs of PID in allergic patients and the mechanism of allergy combined with PID, and then summarizes the common types of PID in allergic patients, the evaluation, treatment and prevention in patients with PID and allergy.

[Clinical analysis of penetrating keratoplasty for infants with congenital corneal opacity].

Objective: To investigate the corneal graft survival and related risk factors of primary penetrating keratoplasty in congenital corneal opacity infants. Methods: It was a retrospective cohort study. Data were collected from forty-two infants (51 eyes) who were aged ≤12 months and diagnosed with congenital corneal opacity in Beijing Tongren Hospital and Beijing Anzhen Hospital from January 1, 2017 to January 31, 2018. The mean age at surgery was (5.7±2.2) months (3-12 months). The mean follow-up duration was (28.6±2.6) months (24-33 months). All the patients underwent penetrating keratoplasty. The status of the corneal grafts and complications were observed and recorded during the regular follow-up. The survival probabilities were estimated by using the Kaplan-Meier and Log-rank test. The graft survival between different influence factors was analyzed by using the χ2 test. Results: The Kaplan-Meier survival rates for penetrating keratoplasty were 84.3% (43/51) at 6 months, 78.4% (40/51) at 12 months and 60.8% (31/51) at the last follow-up. The presence of corneal neovascularization was significantly correlated with graft failure (χ²=5.264, P=0.022). The graft survival differed between eyes receiving combined surgery and mere penetrating keratoplasty and in eyes with varied surgical indications (P=0.039, <0.01). Increased intraocular pressure (7 eyes, 13.7%) and persistent epithelial defects (7 eyes, 13.7%) were the most common postoperative complications, followed by complicated cataract (4 eyes, 7.8%) and posterior capsule opacification (2 eyes, 3.9%). Conclusions: The graft survival rate was satisfactory following pediatric keratoplasty although it had a tendency to decrease with the follow-up time. Corneal neovascularization was a major risk factor of graft failure. Surgical indications and procedures also had a certain effect on the graft survival.

Doppler-based predictive model for methotrexate resistance in low-risk gestational trophoblastic neoplasia with myometrial invasion: prospective study of 147 patients.

OBJECTIVES: This prospective clinical study aimed to evaluate the vascularization characteristics of low-risk gestational trophoblastic neoplasia (GTN) using Doppler imaging and to develop a predictive model for resistance to methotrexate (MTX). METHODS: Patients with low-risk GTN receiving primary MTX treatment were enrolled from the Women's Hospital, Zhejiang University School of Medicine, Hangzhou, China, from September 2012 to August 2018. The primary endpoint was to develop and internally validate a predictive model for resistance to MTX therapy in these patients. In the training set, clinical features and Doppler hemodynamic parameters before MTX therapy were analyzed using logistic regression to identify independent predictors of MTX resistance, which were integrated into the model. The predictive performance of the model was evaluated by leave-one-out cross-validation in the training dataset and internal validation in an independent-sample test dataset. RESULTS: The entire imaging protocol was completed by 147 eligible patients, of which 110 comprised the training set and 37 the test set. In the training set, cases with myometrial invasion (81.8%; 90/110) showed vascular-enriched areas in the myometrium and high velocity and low impedance ratios of the uterine artery (UtA) compared to cases without myometrial invasion (18.2%; 20/110). On multivariate logistic regression analysis, time-averaged mean velocity in UtA (UtA-TAmean) and the International Federation of Gynecology and Obstetrics (FIGO) score were identified as independent predictors (P = 0.009 and P = 0.043, respectively) of MTX resistance. The Doppler-based predictive model, developed based on the 90 cases with myometrial invasion, was y = -2.95332 + 0.41696 × FIGO score + 0.03551 × UtA-TAmean. The model showed an area under the curve of 0.757 (95% CI, 0.653-0.862) and the optimal cut-off value was 0.50622, which had 45.2% sensitivity and 96.6% specificity. The model stratified patients with low-risk GTN into low (< 10%), intermediate (10-90%) and high (> 90%) probability of MTX resistance, based on the threshold values of -1.59544 and 0.10046. The model had an accuracy of 74.4% (95% CI, 64.5-82.3%) in the cross-validation and 72.7% (95% CI, 55.8-84.9%) in the internal validation. CONCLUSIONS: The Doppler-based predictive model, combining a non-invasive marker of tumor vascularity with the FIGO scoring system, can differentiate cases with low from those with high probability of developing MTX resistance and therefore has the potential to guide treatment options in patients with low-risk GTN and myometrial invasion. © 2020 Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Assessing the impact of drinking water iodine concentrations on the iodine intake of Chinese pregnant women living in areas with restricted iodized salt supply.

PURPOSE: The supply of non-iodized salt and the water improvement project have been conducted to reduce the iodine concentration in drinking water in areas with elevated water iodine. We aimed to assess the impact of water iodine concentration (WIC) on the iodine intake of pregnant women in areas with restricted iodized salt supply, and determine the cutoff values of WIC in areas with non-iodized salt supply. METHODS: Overall, 534 pregnant women who attended routine antenatal outpatient visits in Zibo Maternal and Child Health Hospital in Gaoqing County were recruited. The 24-h urine iodine excretion (UIE) in 534 samples and the iodine concentration in 534 drinking water samples were estimated. Urinary iodine excretion, daily iodine intake, and daily iodine intake from drinking water (WII) were calculated. The relationship between WIC and daily iodine take was analyzed. RESULTS: The median WIC, spot urine iodine concentration (UIC), and 24-h UIE were 17 (6, 226) µg/L, 145 (88, 267) µg/L, and 190 (110, 390) µg/day, respectively. A significant positive correlation was found between WIC and UIE (R2 = 0.265, p < 0.001) and UIC (R2 = 0.261, p < 0.001). The contribution rate of WII to total iodine intake increased from 3.0% in the group with WIC of < 10 µg/L to 45.7% in the group with WIC of 50-99 µg/L. CONCLUSION: The iodine content in drinking water is the major iodine source in pregnant women living in high-water iodine areas where iodized salt supply is restricted. The contribution rate of daily iodine intake from drinking water increases with the increase in water iodine concentration.

Differences in tumour heterogeneity based on dynamic contrast-enhanced MRI between tumour and peritumoural stroma for predicting Ki-67 status of invasive ductal carcinoma.

AIM: To evaluate and compare the heterogeneity of intratumour and peritumour areas in the prediction of Ki-67 of invasive ductal carcinoma (IDC) and the predictive accuracy of different contrast frames based on dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI). MATERIALS AND METHODS: This study included 88 patients with histologically confirmed IDC with 57 patients with high Ki-67 status and 31 patients with low Ki-67 status. All patients underwent DCE-MRI before surgery. A grey-level co-occurrence matrix (GLCM) was performed on slice-matched images from six frames by drawing the region of the interest (ROI) on the inner and outer regions of the tumours. The correlations between texture characteristics and Ki-67 status of lesions were analysed, using the Mann-Whitney test and receiver operating characteristic curve analysis. RESULTS: In the high-Ki-67 group, the entropy was significantly higher than that of the low-Ki-67 group (p<0.001). The entropy obtained, based on the tumour boundary as a band-like area inside and outside at the first post-contrast series, revealed the highest receiver operating characteristic (AUC = 0.765). In the multivariate analysis, a higher entropy value (>4.305; p<0.001) remained independently associated with a high-Ki-67 status after adjustment for menopausal status, tumour size, histologic grade, oestrogen receptor (ER) status, and progesterone receptor (PR) status. The other parameters did not show significant differences between the high- and low-Ki-67 groups. CONCLUSION: Heterogeneity analysis based on DCE-MRI could discriminate between high- and low-Ki-67 status. Texture characteristics from the band-like region inside and outside the tumour boundary could predict the Ki-67 status and showed higher accuracy.

[Bioinformatics analysis of drug-resistant ceRNA in epithelial ovarian cancer].

Objective: To explore the possible biological function of long-chain non-coding RNA (lncRNA) on epithelial ovarian cancer (EOC) drug resistance and the value of new diagnostic markers through bioinformatics analysis, clinical testing and verification methods. Methods: (1) Mining the lncRNA related to EOC and constructing the competing endogenous RNA (ceRNA) regulatory network: comprehensively apply text mining, data prediction and network construction and other bioinformatics methods to establish a potential ceRNA regulatory network related to EOC drug resistance, namely lncRNA-microRNA (miRNA)-mRNA regulatory network. (2) Clinical verification: a total of 95 cancer tissue specimens were collected from EOC patients who underwent cytoreductive surgery at the Affiliated Tumor Hospital of Guangxi Medical University from June 2008 to October 2016, of which 54 were platinum-resistant patients (resistance group), 41 platinum-based drug-sensitive patients (sensitive group). Real-time fluorescent quantitative PCR was used to detect the expression of lncRNA in EOC tissues of the two groups, the effect of lncRNA expression on the prognosis of EOC patients, and the diagnostic efficacy of lncRNA expression on resistance to EOC were also analyzed. Results: (1) Text mining preliminarily screened out 25 differentially expressed lncRNA related to the occurrence and development of EOC, and further subcellular localization analysis found that 8 lncRNA exist in the cytoplasm. Through further data mining, collinear literature analysis and construction of ceRNA, the regulatory network predicts that the two lncRNA molecules, GAS5 and HOTAIR, could serve as key ceRNA molecules. (2) Through real-time fluoressent quantitative PCR verification, it was found that both GAS5 and HOTAIR were highly expressed in drug-resistant EOC tissues, which affects the progression-free survival (PFS) and overall survival (OS) time of patients with drug-resistant EOC independent risk factors (P<0.05). The receiver operating characteristic (ROC) area under the curve (AUC) of GAS5 alone was 0.678, the AUC of HOTAIR alone was 0.863, and the AUC of GAS5 combined with HOTAIR was 0.871, and there were statistically significant differences (all P<0.05). Conclusions: The high expression of GAS5 and HOTAIR is closely related to the drug resistance of EOC, which could be used as a potential predictor of response to chemotherapy. At the same time, the combined detection of GAS5 and HOTAIR has a certain diagnostic efficiency for patients with platinum-resistant EOC. This method of using the ceRNA regulatory network to predict key molecules will provide new ideas for the diagnosis and treatment of EOC.

[Rational use of topical drugs to avoid drug-induced ocular surface injury].

Drug-induced ocular surface injury often occurs in the clinical diagnosis and treatment of eye diseases. Because of concealed clinical manifestations, it is difficult to be distinguished, causing misdiagnosis and mistreatment, and leading to serious corneal and conjunctival damage, and even visual disfunction. In this article, we focus on the mechanism, active prevention and effective treatment of drug-induced ocular surface injury, and propose that the rational use of local eye drugs can effectively reduce or avoid drug-induced ocular surface injury and improve the clinical diagnosis and treatment of eye diseases. (Chin J Ophthalmol, 2021, 57: 561-563).

Dual roles of misshapen/NIK-related kinase (MINK1) in osteoarthritis subtypes through the activation of TGFß signaling.

OBJECTIVE: To identify the role of misshapen/NIK-related kinase (MINK1) in age-related Osteoarthritis (OA) and injury-induced OA, and the effects of enhanced TGFß signaling in these progresses. DESIGN: The effect of MINK1 was analyzed with MINK1 knock out (Mink1-/-) mice and C57BL/6J mice. OA progress was studied in age-related OA and instability-associated OA (destabilization of the medial meniscus, DMM) models. The murine knee joint was evaluated through histological staining, Osteoarthritis Research Society International (OARSI) scores, immunohistochemistry, and µCT analysis. Primary chondrocytes were isolated from wild type and Mink1-/- mice and subjected to osteogenic induction and Western blot analysis. RESULTS: MINK1 is highly expressed during cartilage development and in normal cartilage. Mink1-/- mice displayed markedly lower OARSI scores, aggrecan degradation neoepitope positive cells and increased Safranin O and pSMAD2 staining in aging-related OA model. However, in injury-induced OA, loss of MINK1 accelerates extracellular matrix (ECM) destruction, osteophyte formation, and subchondral bone sclerosis. Accelerated subchondral bone remodeling in Mink1-/- mice was accompanied with increased numbers of nestin-positive mesenchymal stem cells (MSCs) and osterix-positive osteoprogenitors. pSMAD2 staining was increased in the subchondral bone marrow of Mink1-/- mice and overexpression of MINK1 inhibited SMAD2 phosphorylation in vitro. CONCLUSIONS: This study shows for the first time that activation of TGFß/SMAD2 by MINK1 deficiency plays opposite roles in aging-related and injury-induced OA. MINK1 deficiency protects cartilage from degeneration in aging joints through increased SMAD2 activation in chondrocytes, while accelerating OA progress in injury-induced model through enhanced osteogenesis of MSCs in the subchondral bone. These findings provide insights for developing precision OA therapeutics targeting TGFß/SMAD2 signaling.