Chromosome ends initiate homologous chromosome pairing during rice meiosis.

During meiotic prophase I, chromosomes undergo large-scale dynamics to allow homologous chromosome pairing, prior to which chromosome ends attach to the inner nuclear envelope and form a chromosomal bouquet. Chromosome pairing is crucial for homologous recombination and accurate chromosome segregation during meiosis. However, the specific mechanism by which homologous chromosomes recognize each other is poorly understood. Here, we investigated the process of homologous chromosome pairing during early prophase I of meiosis in rice (Oryza sativa) using pooled oligo probes specific to an entire chromosome or chromosome arm. We revealed that chromosome pairing begins from both ends and extends towards the center from early zygotene through late zygotene. Genetic analysis of both trisomy and autotetraploidy also showed that pairing initiation is induced by both ends of a chromosome. However, healed ends that lack the original terminal regions on telocentric and acrocentric chromosomes cannot initiate homologous chromosome pairing, even though they may still enter the telomere clustering region at the bouquet stage. Furthermore, a chromosome that lacks the distal parts on both sides loses the ability to pair with other intact chromosomes. Thus, the native ends of chromosomes play a crucial role in initiating homologous chromosome pairing during meiosis and likely have a substantial impact on genome differentiation.

CD56bright NK cell expansion correlated with EBV reactivation control post allogeneic hematopoietic stem cell transplantation.

Natural killer (NK) cells are equipped with anti-Epstein-Barr virus (EBV) function, however, whether EBV infection will affect NK cells reconstitution after allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains unclear. To identify the characteristics of NK cells, we prospectively enrolled 11 patients who occurred EBV reactivation post allo-HSCT and 11 patients without EBV infection as control. We found that that EBV infection induced the expansion of CD56bright and NKG2A+KIR- NK subsets,and decreased the cytotoxicity function of NK cells. The frequency of NKG2A+KIR- NK cells were higher in patients who progressed into post-transplant lymphoproliferative disorder (PTLD) than EBV viremia patients, which also correlated with decreased proliferation and cytotoxic function. By screening the activation receptors of NK cells, we found the DNAM-1+CD56bright NK cells is significantly increased after EBV stimulation, further we demonstrated that DNAM-1 is essential for EBV induced NK cells activation as the cytokine release against EBV-transformed lymphoblastoid cell lines(EBV-LCLs) of CD56bright NK cells were significantly decreased after DNAM-1 blockade. NK cells infusion suppressed the progression of EBV-related tumor mice model. A prospective cohort indicated that old donor age was an independent risk factor for EBV infection. Rapid CD56bri expansion and high expression of DNAM-1 on CD56bri NK cells in response to EBV reactivation correlated with rapid EBV clearance post allo-HSCT in patients with younger donors. In summary, our data showed that high expression of DNAM-1 receptors on NK cell may participate protective CD56bri NK cells response to EBV infection after allo-HSCT.

CT-guided microcoil localization of pulmonary nodules before VATS: clinical experience in 1059 patients.

OBJECTIVE: To retrospectively evaluate the efficacy and safety of CT-guided microcoil localization of pulmonary nodules before video-assisted thoracoscopic surgery (VATS). METHODS: A total of 1059 consecutive patients with 1331 pulmonary nodules treated between July 2018 and April 2021 were included in this study. Of the 1331 nodules, 1318 were localized using the tailed method and 13 were localized using the non-tailed method. The localization technical success rate and complications of the microcoil localization procedure were assessed. Univariate and multivariate logistic regression analyses were used to determine potential risk factors for technical failure, pneumothorax, and pulmonary hemorrhage. RESULTS: The technical success rate of the localization procedure was 98.4% (1310/1331 nodules). Nodule location in the lower lobes (p = 0.015) and need for a longer needle path (p < 0.001) were independent predictors of technical failure. All localization procedure-related complications were minor (grade 1 or 2) adverse events, with the exception of one grade 3 complication. The most common complications were pneumothorax (302/1331 nodules [22.7%]) and pulmonary hemorrhage (328/1331 nodules [24.6%]). Male sex (p = 0.001), nodule location in the middle (p = 0.003) and lower lobes (p = 0.025), need for a longer needle path (p < 0.001), use of transfissural puncture (p = 0.042), and simultaneous multiple localizations (p < 0.001) were independent risk factors for pneumothorax. Female sex (p = 0.015), younger age (p = 0.023), nodules location in the upper lobes (p = 0.011), and longer needle path (p < 0.001) were independent risk factors for pulmonary hemorrhage. CONCLUSIONS: CT-guided microcoil localization of pulmonary nodules before VATS using either the tailed or non-tailed method is effective and safe. CLINICAL RELEVANCE STATEMENT: CT-guided microcoil localization of pulmonary nodules before VATS resection is effective and safe when using either the tailed or non-tailed method. Nodules requiring transfissural puncture and multiple nodules requiring simultaneous localizations can also be successfully localized with this method. KEY POINTS: • Pre-VATS CT-guided microcoil localization of pulmonary nodules by tailed or non-tailed method was effective and safe. • When the feasible puncture path was beyond the scope of wedge resection, localization could be performed using the non-tailed method. • Although transfissural puncture and simultaneous multiple localization were independent risk factors for pneumothorax, they remained clinically feasible.

Predicting short-term and long-term mortalities from sepsis in patients who receive allogeneic haematopoietic stem cell transplantation.

Patients who receive allogeneic haematopoietic stem cell transplantation (allo-HSCT) may develop sepsis, which result in a highly intensive care unit admission rate and mortality. Therefore, short-term and long-term prognostic models for sepsis after allo-HSCT are urgently needed. We enrolled patients receiving allo-HSCT who developed sepsis after allo-HSCT at Peking University People's Hospital between 2012 and 2021, including 287 patients who received allo-HSCT in 2018-2021 in the derivation cohort, and 337 patients in 2012-2017 in the validation cohort. Multivariate logistic regression analysis was used to identify prognostic factors, and these identified factors were incorporated into two scoring models. Seven independent factors (acute graft-versus-host disease (GVHD), chronic GVHD (cGVHD), total bilirubin, lactate dehydrogenase (LDH) and organ dysfunction [renal, lung and heart]) were included in the 6-month prognostic model, and six factors (cGVHD, C-reactive protein, LDH, organ dysfunction [lung, neurologic and coagulation]) were included in the 14-day prognostic model. The area under the receiver operating characteristic curves, calibration plots and decision curve analysis demonstrated the robust predictive performance of the models, better than the Sequential Organ Failure Assessment score. Early identification of patients with high risk of 6-month and 14-day death may allow clinicians to provide timely treatments and improve the therapeutic effects.

Rational Construction of a Novel Bioluminescent Substrate for Sensing the Tumor-Associated Hydrolase Notum.

Notum, one of the key serine hydrolases in mammals, hydrolyzes the palmitoleoyl moieties of many important proteins and modulates multiple signaling pathways including Wnt/ß-catenin signaling. Notum is tightly associated with multiple human diseases, but the reliable and practical tools for sensing Notum activities in complex biological systems are rarely reported. Herein, an efficient strategy was used to rationally construct a specific bioluminescent substrate for Notum. Following computer-aided molecular design and experimental verification, octanoyl luciferin (OL) was selected as the optimum substrate for human Notum, with excellent specificity, high detection sensitivity and high signal-to-noise ratio. Under physiological conditions, OL was readily hydrolyzed by Notum or Notum-containing biological specimens to release d-luciferin that could be easily detected by various fluorescence devices in the presence of luciferase. The applicability of OL for real-time sensing native Notum was examined in living cells, extracellular matrix, and tissue preparations. OL was also used for constructing a high-throughput assay for screening of Notum inhibitors, while a natural compound (bergapten) was newly identified as a potent Notum inhibitor. Collectively, this study devises a reliable and easy-to-use tool for sensing Notum activities in biological systems, which will strongly facilitate hNotum-associated fundamental studies, disease diagnosis, and drug discovery.

Burden of liver complications related to non-alcoholic fatty liver disease in China from 2005 to 2019: Observations from the Global Burden of Disease Study, 2019.

AIM: To assess the burden of liver complications related to non-alcoholic fatty liver disease (LC-NAFLD) from 2005 to 2019 in China. MATERIALS AND METHODS: We used data from the Global Burden of Disease, Injuries, and Risk Factors Study, 2019, to present contemporary and varying profiles of China's LC-NAFLD burden. The Joinpoint Regression model and Gaussian process regression were, respectively, used to estimate the annual percentage change in prevalence rates and disability-adjusted life-year (DALY) rates, and the relationship between the sociodemographic index (SDI) and age-standardized rates of LC-NAFLD. RESULTS: In 2019, China had 293.42 million (95% uncertainty interval [UI]: 263.69-328.44) LC-NAFLD cases with a prevalence rate and DALYs of 20.63 (95% UI: 23.09-18.54) per 1000 people and 591.03 thousand (95% UI: 451.25-737.33), respectively. North China had the highest prevalence but the lowest DALYs of LC-NAFLD, whereas Southwest China had the lowest prevalence but the highest DALYs. LC-NAFLD were more common in men than in women (male: female ratio, 1.27) in 2019. From 2005 to 2019, the prevalence of NAFLD cases increased by 68.32% (from 174.32 million in 2005 to 293.42 million in 2019), mainly because of an age-specific prevalence rate increase. CONCLUSION: The LC-NAFLD burden in China is substantial and has increased markedly over the past 15 years. Effective measures for low SDI regions and men are needed to address the rapidly increasing NAFLD burden.

Optical Temperature Sensing Based on Linear Change of Luminescence Intensity Ratio in Y2O3: Tm3+, Eu3+ Phosphors.

In this work, Y2O3: Tm3+, Eu3+ phosphors were made by homogeneous precipitation with urea as precipitator. The emission spectra varying with temperature of Y2O3: Tm3+, Eu3+ phosphors were measured and analyzed. Analysis show that the luminescence of Eu3+ represents a normal thermal quenching change, while that of Tm3+ exhibits slow thermal enhancement phenomenon. In the temperature range of 303-503 K, the luminescence of Tm3+ showed a trend of first strengthening and then weakening. The reason for this phenomenon of Tm3+ is that there is energy transfer from Eu3+ to Tm3+, and the energy transfer efficiency increases gradually with temperature. Meanwhile, the luminescence of Tm3+ also have thermal quenching effect. Under the combined influence of thermal quenching and energy transfer, the luminescence of Tm3+ first becomes stronger and then then becomes weaker. According to the calculation, the luminescence intensity ratio (LIR) of Tm3+ and Eu3+ conforms to the linear empirical formula with increasing temperature. The relative sensitivity of phosphors decreases with Eu3+ concentration increased, and the maximum Sr reaches 0.460% K-1 (1% Tm3+, 0.3% Eu3+, at 303 K). Moreover, the temperature cycle test present that the LIR of phosphors has good repeatability.

Contact area and pressure changes of patellofemoral joint during stair ascent and stair descent.

PURPOSE: To investigate the differences of patellofemoral joint pressure and contact area between the process of stair ascent and stair descent. METHODS: The finite element models of 9 volunteers without disorders of knee (9 males) to estimate patellar cartilage pressure during the stair ascent and the stair descent. Simulations took into account cartilage morphology from magnetic resonance imaging, joint posture from weight-bearing magnetic resonance imaging, and ligament model. The three-dimension models of the patella, femur and tibia were developed with the medical image processing software, Mimics 11.1. The ligament was established by truss element of the non-linear FE solver. The equivalent gravity direction (-z direction) load was applied to the whole end of femur (femoral head) according to the body weight of the volunteers, and the force of patella was observed. A paired-samples t-test or Wilcoxon rank sum test to make comparisons between stair ascent and stair descent. Statistical analyses were performed using SPSS 22.0 using a P value of 0.05 to indicate significance. RESULTS: During the stair descent (knee flexion at 30°), the contact pressure of the patella was 2.59 ± 0.06Mpa. The contact pressure of femoral trochlea cartilage was 2.57 ± 0.06Mpa. During the stair ascent (knee flexion at 60°), the contact pressure with patellar cartilage was 2.82 ± 0.08Mpa. The contact pressure of the femoral trochlea cartilage was 3.03 ± 0.11Mpa. The contact area between patellar cartilage and femoral trochlea cartilage was 249.27 ± 1.35mm2 during the stair descent, which was less than 434.32 ± 1.70mm2 during the stair ascent. The area of high pressure was located in the lateral area of patella during stair descent and the area of high pressure was scattered during stair ascent. CONCLUSION: There are small change in the cartilage contact pressure between stair ascent and stair descent, indicating that the joint adjusts the contact pressure by increasing the contact area.

The influence of varus and valgus deviation on the contact area of patellofemoral joint in healthy knees.

OBJECT: Varus-valgus lower alignment is a risk factor for patellofemoral osteoarthritis, but malalignment alone affect not only the tibiofemoral joint but also the patellofemoral joint. The aim of the present study was to analyse the contact area of patellofemoral joint in varus alignment and valgus alignment of healthy subjects using magnetic resonance imaging. METHODS: Twenty-six healthy subjects with valgus lower limb alignment (Group I, n = 26) and twenty-six volunteers with varus lower limb alignment (Group II, n = 26) was performed. An MRI scan was used to capture and measure the patellofemoral joint articular cartilage contact area at different degrees of knee flexion (20°, 40°,60°) in passive movement. All subjects were categorized on the basis of the global limb alignment and mechanical alignment of the femur and tibia. Varus alignment is hip-knee-ankle angle ≥ 3°; and valgus alignment is hip-knee-ankle angle ≥ - 3°. To obtain medial facet contact area and lateral facet contact area for each slice, the length of each respective line of contact was multiplied by the 5 mm slice thickness. RESULTS: The overall joint contact area increased from 168.0 ± 20.5 mm2 at 20° knee flexion to 334.4 ± 30.5 mm2 at 60° knee flexion in group (I) The overall joint contact area increased from 178.0 ± 18.9 mm2 at 20° knee flexion to 328.9 ± 27.2 mm2 at 60° knee flexion in group (II) There was a significant difference in lateral facet contact area between group I and group II at 40° of knee flexion. There was significantly different in medial facet contact area between group I and group II at 20° and 40° of knee flexion. CONCLUSIONS: Throughout the knee movement, the contact area on the lateral facet of the patellofemoral joint was greater in the valgus group. In the early phase of knee flexion, the contact area of the medial patellofemoral joint was larger in the varus group. Lower alignment is an important factor in patellofemoral joint degeneration.

Continuous current-injected waveforms shaping for suppressing relaxation oscillations of direct modulation based on equivalent circuit model.

An improved technique of continuous shaping current-injected waveforms based on the single-mode rate equations is proposed to suppress relaxation oscillations (ROs) from direct modulation of distributed feedback laser (DFB). The signal expression of shaping current is deduced theoretically from the dependence of DFB desired output waveforms in detail, and the specific parameters derivation of the different polynomial degree is also discussed necessarily. Furthermore, a polynomial p-function with inverse operation is adopted to construct the Fourier series corresponding to injection current waveform signal. The equivalent circuit model with DFB phenomenological description is injected into shaping current signal to verity the proposed validity by evaluating the static and dynamic characteristics. The simulation results of the optimized shaping signal show the good agreement with the desired output pulse including rising and falling edge and suppress the ROs amplitude dramatically at the two jump edges.

Copper(I)-Catalyzed Syntheses of Benzo[b]fluorenes by the Cascade Reactions of 2-Alkynylbenzaldehyde N-Tosylhydrazones and Aromatic Terminal Alkynes.

Benzo[b]fluorenes were synthesized via CuI-catalyzed cascade reactions of 2-alkynylbenzaldehyde N-tosylhydrazones and aromatic terminal alkynes in the presence of base including the formation of the benzoenyne-allene intermediate in situ and its Schmittel cyclization. Density functional theory calculation was performed to give the energy difference for the formation of 5-phenyl-11H-benzo[b]fluorene and 1,2-diphenyl-1H-cyclobuta[a]indene from the proposed diradical intermediates.

Development of a one-step multiplex qRT-PCR assay for the detection of African swine fever virus, classical swine fever virus and atypical porcine pestivirus.

BACKGROUND: African swine fever virus (ASFV), classical swine fever virus (CSFV) and atypical porcine pestivirus (APPV) have caused great economic losses to the swine industry in China. Since coinfections of ASFV, CSFV and APPV occur in certain pig herds, it is necessary to accurately and differentially detect these pathogens in field-collected samples. In this study, a one-step multiplex real-time quantitative reverse transcription-polymerase chain reaction (multiplex qRT-PCR) was developed for the simultaneous and differential detection of ASFV, CSFV and APPV. RESULTS: The one-step multiplex qRT-PCR presented here was able to simultaneously detect ASFV, CSFV and APPV but could not amplify other viruses, including porcine circovirus type 2 (PCV2), pseudorabies virus (PRV), porcine reproductive and respiratory syndrome virus (PRRSV), foot-and-mouth disease virus (FMDV), porcine parvovirus (PPV), porcine epidemic diarrhoea virus (PEDV), transmissible gastroenteritis virus (TGEV), porcine rotavirus (PRoV), porcine deltacoronavirus (PDCoV), border disease virus (BDV), bovine viral diarrhoea virus type 1 (BVDV-1), BVDV-2, etc. The limit of detection (LOD) of the assay was 2.52 × 101 copies/µL for ASFV, CSFV and APPV. A repeatability test using standard recombinant plasmids showed that the intra- and interassay coefficients of variation (CVs) were less than 2%. An assay of 509 clinical samples collected in Guangxi Province, southern China, from October 2018 to December 2020 showed that the positive rates of ASFV, CSFV and APPV were 45.58, 12.57 and 3.54%, respectively, while the coinfection rates of ASFV and CSFV, ASFV and APPV, CSFV and APPV were 4.91, 1.38, 0.98%, respectively. Phylogenetic analysis based on the nucleotide sequences of the partial ASFV p72 gene showed that all ASFV strains from Guangxi Province belonged to genotypes I and II. CONCLUSION: A one-step multiplex qRT-PCR with high specificity, sensitivity and repeatability was successfully developed for the simultaneous and differential detection of ASFV, CSFV and APPV.

The optimal time for the initiation of in vitro fertilization and embryo transfer among women with atypical endometrial hyperplasia and endometrial carcinoma receiving fertility-sparing treatment.

OBJECTIVE: To explore the optimal time for initiating in vitro fertilization and embryo transfer (IVF-ET) in women with complete remission after fertility-sparing treatment for grade I endometrial cancer (EC) or atypical endometrial hyperplasia (AEH). PATIENTS AND METHODS: Young women who demonstrated complete remission after fertility-sparing treatment for grade I EC or AEH and underwent IVF-ET treatment were included. A generalized estimating equation (GEE) was used to compare the outcomes of controlled ovarian hyperstimulation (COH) and embryo transfer at different times after discontinuing high-dose progesterone therapy, and patients were divided into three groups: ≤ 3 months (time 1), 3-9 months (time 2) and > 9 months (time 3). RESULTS: Thirty-seven women with complete remission after fertility-sparing treatment for grade I EC or AEH underwent 75 IVF-ET cycles. Regarding initiation of COH, 10 cycles for time 1, 31 cycles for time 2 and 34 cycles for time 3 were included. The odds ratios (95% confidence intervals) for the number of available embryos at time 2 and time 3 were 1.82 (1.08-3.08) and 2.45 (1.39-4.33), and those for the number of high-quality embryos at time 2 and time 3 were, respectively, 3.64 (1.34-9.87) and 3.62 (1.10-11.91), compared with that at time 1. Nineteen (51.4%) women had at least one clinical pregnancy and 13 (35.1%) women had live births. During a median follow-up period of 51 months (range 5-168 months), 10 (27.0%) women had disease relapse, with a median interval of 15.5 months (range 5-104 months). CONCLUSION: Initiating IVF-ET 3 months after ceasing high-dose progesterone therapy can lead to better outcomes of controlled ovarian hyperstimulation for women with endometrial cancer or atypical endometrial hyperplasia.

Genome-wide identification and analysis of class III peroxidases in Betula pendula.

BACKGROUND: Class III peroxidases (POD) proteins are widely present in the plant kingdom that are involved in a broad range of physiological processes including stress responses and lignin polymerization throughout the plant life cycle. At present, POD genes have been studied in Arabidopsis, rice, poplar, maize and Chinese pear, but there are no reports on the identification and function of POD gene family in Betula pendula. RESULTS: We identified 90 nonredundant POD genes in Betula pendula. (designated BpPODs). According to phylogenetic relationships, these POD genes were classified into 12 groups. The BpPODs are distributed in different numbers on the 14 chromosomes, and some BpPODs were located sequentially in tandem on chromosomes. In addition, we analyzed the conserved domains of BpPOD proteins and found that they contain highly conserved motifs. We also investigated their expression patterns in different tissues, the results showed that some BpPODs might play an important role in xylem, leaf, root and flower. Furthermore, under low temperature conditions, some BpPODs showed different expression patterns at different times. CONCLUSIONS: The research on the structure and function of the POD genes in Betula pendula plays a very important role in understanding the growth and development process and the molecular mechanism of stress resistance. These results lay the theoretical foundation for the genetic improvement of Betula pendula.

Upregulation of SNTB1 correlates with poor prognosis and promotes cell growth by negative regulating PKN2 in colorectal cancer.

BACKGROUND: Colorectal cancer (CRC) is one of the most highly malignant tumors and has a complicated pathogenesis. A preliminary study identified syntrophin beta 1 (SNTB1) as a potential oncogene in CRC. However, the clinical significance, biological function, and underlying mechanisms of SNTB1 in CRC remain largely unknown. Thus, the present study aimed to investigate the role of SNTB1 in CRC. METHODS: The expression profile of SNTB1 in CRC samples was evaluated by database analysis, cDNA array, tissue microarray, quantitative real-time PCR (qPCR), and immunohistochemistry. SNTB1 expression in human CRC cells was silenced using short hairpin RNAs (shRNA)/small interfering RNAs (siRNA) and its mRNA and protein levels were assessed by qPCR and/or western blotting. Cell viability, survival, cell cycle, and apoptosis were determined by the CCK-8 assay, colony formation, and flow cytometry assays, respectively. A xenograft nude mouse model of CRC was established to validate the roles of SNTB1 in vivo. Immunohistochemistry and TUNEL staining were used to determine the expression of SNTB1, PCNA, and cell apoptosis in tissue samples. Isobaric tag for relative and absolute quantification (iTRAQ) was used to analyze the differentially expressed proteins after knockdown of SNTB1 in CRC cells. Silence of protein kinase N2 (PKN2) using si-PNK2 was performed for rescue experiments. RESULTS: SNTB1 expression was increased in CRC tissues compared with adjacent noncancerous tissues and the increased SNTB1 expression was associated with shorter overall survival of CRC patients. Silencing of SNTB1 suppressed cell viability and survival, induced cell cycle arrest and apoptosis in vitro, and inhibited the growth of CRC cells in vivo. Further elucidation of the regulation of STNB1 on CRC growth by iTRAQ analysis identified 210 up-regulated and 55 down-regulated proteins in CRC cells after SNTB knockdown. A PPI network analysis identified PKN2 as a hub protein and was up-regulated in CRC cells after SNTB1 knockdown. Western-blot analysis further confirmed that SNTB1 knockdown significantly up-regulated PKN2 protein expression in CRC cells and decreased the phosphorylation of both ERK1/2 and AKT. Moreover, rescue experiments indicated that PKN2 knockdown significantly rescued SNTB1 knockdown-mediated decrease in cell viability, survival, and increase of cell cycle arrest at G0/G1 phase and apoptosis of CRC cells. CONCLUSIONS: These findings indicate that SNTB1 is overexpressed in CRC. Elevated SNTB1 levels are correlated with shorter patient survival. Importantly, SNTB1 promotes tumor growth and progression of CRC, possibly by reducing the expression of PKN2 and activating the ERK and AKT signaling pathway. Our study highlights the potential of SNTB1 as a new prognostic factor and therapeutic target for CRC.

Simultaneous preoperative computed tomography-guided microcoil localizations of multiple pulmonary nodules.

OBJECTIVES: To evaluate retrospectively the feasibility and safety of simultaneous multiple microcoil localizations of multiple pulmonary nodules prior to video-assisted thoracoscopic surgery (VATS). METHODS: This retrospective cohort study enrolled 288 consecutive patients, who underwent computed tomography (CT)-guided microcoil localization and subsequent VATS at our academic hospital between July 2017 and June 2018. Of these patients, 36 with 79 pulmonary nodules undergoing simultaneous multiple microcoil localizations in the ipsilateral lung were designated the multiple localization group; the remaining 252 with 252 pulmonary nodules undergoing single microcoil localization were designated the single localization group. The main outcomes were the technical success and complication rates of the localization procedures. The Student t test and Mann-Whitney U test were used for continuous variables. The chi-squared test and logistic regression analysis were used to assess dichotomous variables. RESULTS: The localization technical success rates of the multiple and single localization groups were 96.2% (76/79) and 98.0% (247/252), respectively (p = 0.326). The rate of any complication (pneumothorax or pulmonary hemorrhage) was significantly higher in the multiple localization than in the single localization group (55.6% vs 21.8%, respectively; p < 0.001). The incidence of pneumothorax was significantly higher in the multiple localization than in the single localization group (p < 0.001). The difference between the incidence of pulmonary hemorrhage in the 2 groups was not significant (p = 0.385). CONCLUSIONS: Although preoperative CT-guided simultaneous microcoil localizations of multiple pulmonary nodules produced a significantly higher incidence of pneumothorax, the localizations were clinically feasible and safe. KEY POINTS: • Simultaneous preoperative CT-guided microcoil localizations of multiple pulmonary nodules are clinically feasible and safe. • Simultaneous microcoil localizations of multiple pulmonary nodules produced a significantly higher incidence of pneumothorax.

Prediction of postpartum hemorrhage in pregnant women with immune thrombocytopenia: Development and validation of the MONITOR model in a nationwide multicenter study.

Globally, postpartum hemorrhage (PPH) is the leading cause of maternal death. Women with immune thrombocytopenia (ITP) are at increased risk of developing PPH. Early identification of PPH helps to prevent adverse outcomes, but is underused because clinicians do not have a tool to predict PPH for women with ITP. We therefore conducted a nationwide multicenter retrospective study to develop and validate a prediction model of PPH in patients with ITP. We included 432 pregnant women (677 pregnancies) with primary ITP from 18 academic tertiary centers in China from January 2008 to August 2018. A total of 157 (23.2%) pregnancies experienced PPH. The derivation cohort included 450 pregnancies. For the validation cohort, we included 117 pregnancies in the temporal validation cohort and 110 pregnancies in the geographical validation cohort. We assessed 25 clinical parameters as candidate predictors and used multivariable logistic regression to develop our prediction model. The final model included seven variables and was named MONITOR (maternal complication, WHO bleeding score, antepartum platelet transfusion, placental abnormalities, platelet count, previous uterine surgery, and primiparity). We established an easy-to-use risk heatmap and risk score of PPH based on the seven risk factors. We externally validated this model using both a temporal validation cohort and a geographical validation cohort. The MONITOR model had an AUC of 0.868 (95% CI 0.828-0.909) in internal validation, 0.869 (95% CI 0.802-0.937) in the temporal validation, and 0.811 (95% CI 0.713-0.908) in the geographical validation. Calibration plots demonstrated good agreement between MONITOR-predicted probability and actual observation in both internal validation and external validation. Therefore, we developed and validated a very accurate prediction model for PPH. We hope that the model will contribute to more precise clinical care, decreased adverse outcomes, and better health care resource allocation.

Risk stratification and outcomes of intracranial hemorrhage in patients with immune thrombocytopenia under 60 years of age.

Intracranial hemorrhage (ICH) is a devastating complication of immune thrombocytopenia (ITP). However, information on ICH in ITP patients under the age of 60 years is limited, and no predictive tools are available in clinical practice. A total of 93 adult patients with ITP who developed ICH before 60 years of age were retrospectively identified from 2005 to 2019 by 27 centers in China. For each case, 2 controls matched by the time of ITP diagnosis and the duration of ITP were provided by the same center. Multivariate analysis identified head trauma (OR = 3.216, 95%CI 1.296-7.979, P =.012), a platelet count ≤ 15,000/µL at the time of ITP diagnosis (OR = 1.679, 95%CI 1.044-2.698, P =.032) and severe/life-threatening bleeding (severe bleeding vs. mild bleeding, OR = 1.910, 95%CI 1.088-3.353, P =.024; life-threatening bleeding vs. mild bleeding, OR = 2.620, 95%CI 1.360-5.051, P =.004) as independent risk factors for ICH. Intraparenchymal hemorrhage (OR = 5.191, 95%CI 1.717-15.692, P =.004) and a history of severe bleeding (OR = 4.322, 95%CI 1.532-12.198, P =.006) were associated with the 30-day outcome of ICH. These findings may facilitate ICH risk stratification and outcome prediction in patients with ITP.

Significance of serum and pathological biomarkers in fertility-sparing treatment for endometrial cancer or atypical hyperplasia: a retrospective cohort study.

BACKGROUND: This study analyzed the changes of serum and pathological biomarkers during fertility-sparing therapy of endometrial cancer (EC) or endometrial atypical hyperplasia (EAH), to investigate their implications for early prediction of treatment efficacy. METHODS: A retrospective analysis of EC or EAH patients who received fertility-sparing therapy between 2012 and 2016 was performed. Serum and endometrium sampling were obtained for each patient at three time points: at baseline, at 3-6 months' treatment and at the end of conservative treatment. Serum biomarkers including insulin resistance (HbA1c, HOMA-IR), sex hormones and thyroid hormones were measured. Meanwhile expression of endometrial pathological biomarkers including ER, PR, PRB and Ki-67 was also assessed by immunohistochemistry. RESULTS: For the 53 recruited patients, overall complete response, recurrence and pregnancy rates were 94%, 26% and 36.4%. During the treatment, the serum biomarkers of HOMA-IR remained stable, while pathological markers including PR, PRB and Ki67 diminished significantly. Patients who achieved remission faster had significant lower HOMA-IR level and higher PRB expression at baseline. We also found a more remarkable down-regulation of PRB related with faster remission. Further multivariate analysis confirmed that baseline HOMA-IR ≥ 2.5 negatively affected treatment time to remission (OR 0.206; p = 0.017). While marked reduction of PRB (≥ 30%) at 3-6 months' treatment correlated with faster remission (OR 5.788; p = 0.010). CONCLUSION: For EC and EAH patients who received fertility-sparing therapy, baseline status of insulin resistance predicted poor response to progestin, while marked reduction of PRB following the initial 3-6 months' treatment predicted fast remission.

Poly (adenosine diphosphate [ADP]-ribose) polymerase (PARP) inhibitors as maintenance therapy in women with newly diagnosed ovarian cancer: a systematic review and meta-analysis.

PURPOSE: To investigate the efficacy and safety of poly (adenosine diphosphate [ADP]-ribose) polymerase (PARP) inhibitors (including their different types) as maintenance therapy in women with newly diagnosed ovarian cancer, and to explore whether this therapy produces a survival benefit in a subgroup population with specific clinical characteristics. METHODS: We searched MEDLINE, EMBASE, the Cochrane Library, Web of Science and relevant clinical research registry platforms on October 1, 2019, and included randomized controlled trials (RCTs) that compared PARP inhibitors with placebo in women (aged ≥ 18 years) with newly diagnosed epithelial ovarian cancer. RESULTS: We identified four RCTs with 3,070 participants. Compared with placebo, PARP inhibitor maintenance therapy showed a clinically significant benefit on progression free survival (PFS) in homologous recombination deficiency (HRD) positive population (hazard ratio [HR], 0.39; 95% confidence interval [CI], 0.29-0.53). In contrast, no clear differences were identified between the groups in the HRD negative population (HR, 0.83; 95% CI 0.67-1.03). Further, there was no clear difference between the groups in terms of other outcomes (overall survival, health-related quality of life, and adverse events). CONCLUSIONS: PARP inhibitor maintenance therapy significantly prolongs the PFS of patients with newly diagnosed ovarian cancer, especially in HRD positive patients. The diagnostic test used to determine HRD status plays an important role in guiding PARP inhibitor maintenance therapy. Compared with placebo, the effect of PARP inhibitors on ovarian cancer was probably not affected by the International Federation of Gynecology and Obstetrics stage status, response to first-line chemotherapy, and residual macroscopic disease after debulking surgery.