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Objective: To assess the correlation between atmospheric pollutants, meteorological factors, and emergency department visits for respiratory diseases in Haikou City. Methods: Daily data on atmospheric pollutants, meteorological factors, and emergency department visits for respiratory diseases in Haikou City from 2018 to 2021 were collected. The Spearman rank correlation test was used to analyze the correlation, and a distributed lag non-linear model was employed to analyze the health effects and lag impacts of environmental factors. Subgroup analyses were conducted based on sex and age. Results: According to the criteria of International Classification of Diseases (ICD-10: J00-J99), a total of 221 913 cases were included, accounting for 21.3% of the total emergency department visits in Haikou City. For every 1 °C increase in temperature, the risk of emergency department visits increased by 1.029% (95% CI 1.016%-1.042%). Relative humidity greater than 80% reduced the risk of visits, while higher atmospheric pressure (>1 010 hpa) also decreased the likelihood of daily emergency department visits. Higher concentrations of PM25 (30-50 μg/m3), PM10 (>60 μg/m3), and O3 (75-125 μg/m3) were associated with increased visits. Higher temperatures (>25 °C) have a greater impact on females and children aged 0-14 years, while males are more sensitive to low atmospheric pressure. Individuals aged 65 and above exhibited increased sensitivity to O3 concentration, and the effects of PM2.5, PM10, and O3 are more pronounced in individuals over 14 years old. Conclusions: Short-term exposure to high temperatures, particulate matter pollutants (PM25 and PM10), and ozone (O3) is associated with increased emergency department visits for respiratory diseases.

Objectives: The purpose of this review is to summarize the characteristics and applications of current hysteroscopic training models. Methods: We conducted a systematic search of PubMed, Embase, and Cochrane Library for eligible studies published before March 2024. Manual screening of references and citation tracking were also performed. Results: Reported hysteroscopic training models included virtual reality simulators, non-biological material models, plant tissue models, animal tissue models, and human tissue models. No training model was distinctly superior in terms of realism, haptic feedback, availability of standardized scoring of operations, preparation difficulty, reusability of surgical procedure, and prices. Utilizing any type of models for hysteroscopy simulation training could assist trainees in enhancing relevant knowledge, skills, self-confidence, and comfort, but virtual reality models had an advantage in training capacity. Conclusions: Each hysteroscopic training model has its advantages and disadvantages. An appropriate training curriculum is needed to efficiently leverage the merits of different models. The realism and training effectiveness of various training models need to be compared using rigorously designed studies and standard evaluation tools.

Abstract Background Cervical cancer is the fourth most common cancer among women, with persistent high-risk human papillomavirus (HPV) infection being responsible for its progression. In healthy, pre-menopausal women, the vaginal pH value is maintained at 3.8–4.5, but various factors can affect it. Previous studies have suggested the relationship between vaginal pH value and HPV infection. In this study, we aimed to explore the relationship between vaginal pH and susceptibility of HPV infection. Methods In our study, we retrospectively collected medical information from women who underwent leukorrhea examination at our hospital. We excluded women with infectious diseases or cancer, those who were pregnant or within 6 months post-delivery, and those without HPV test results within 6 months. The association between percentage of HPV infection and vaginal pH value was analyzed. Furthermore, we prepared HPV pseudovirus (PsVs) by co-transfecting structure plasmids and report plasmids in 293FT cells. In vitro, we changed the pH value of cell culture medium to investigate its influence on HPV PsVs infection. In vivo, we changed mouse’s vaginal pH value to investigate its influence on HPV PsVs infection. Results Our retrospective study included 3115 women aged 20–78, including 2531 women with HPV negative and 584 women with HPV positive. The percentages of both HPV infection and high-risk HPV infection were higher in women with a vaginal pH value ≥5.0 compared to those with a pH value

Abstract Background Esketamine, recognized for its analgesic, sedative, and anti-inflammatory qualities, is integral in multimodal analgesia. However, the potential opioid-sparing effects of intravenous esketamine, along with its impact on inflammatory responses, and cognitive function during laparoscopic surgery, remain unexplored. Methods In this study, 90 patients scheduled for laparoscopic cholecystectomy were equally randomized into three groups: a normal saline control group (NS), a low-dose esketamine group (LS) and a high-dose esketamine group (HS). Subsequently, we monitored several parameters: hemodynamics, levels of stress and inflammatory responses, intraoperative doses of sufentanil, remifentanil, and propofol, and 24-hour postoperative sufentanil requirements. We also evaluated alterations in cognitive function, perioperative indicators, and potential adverse reactions among the three groups. Results Compared to their levels 5 minutes prior to anesthesia (T0) and 30 minutes post-operation (T4), the NS group exhibited a more significant decrease in Mean Arterial Pressure (MAP) and Heart Rate (HR) at various time intervals: 5 minutes after the skin incision (T1), 30 minutes post-incision (T2), and at the conclusion of the operation (T3), compared to the LS and HS groups(P

Abstract Background Anti-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) encephalitis, a rare subtype of autoimmune encephalitis (AE), is often found associated with tumors such as thymoma, lung cancer, ovarian tumors, and breast cancer, and the tumors were generally detected during the screening process after the encephalitis initiated. The tumor is considered a trigger of AE, but the mechanism remains unclear. Case Presentation A 53-year-old woman presented short-term memory loss two days after the primary cytoreduction for high-grade serous ovarian cancer (HGSOC, FIGO stage IC3). Cell-based assay found AMPAR CluA2 IgG positive in both serum (1:3.2) and cerebrospinal fluid (1:32). Moreover, mild AMPAR GluA1 and strong GluA2 expressions were also found positive in the paraffin sections of ovarian tumor tissue, indicating the ovarian cytoreduction surgery might stimulate the release of receptor antigens into the circulation system. The patient’s condition deteriorated within two weeks, developing consciousness and autonomic dysfunction, leading to ICU admission. With oral steroids, intravenous immunoglobulin, plasmapheresis, and rituximab treatment, the patient’s consciousness markedly improved after three months. Conclusion We presented the first case of anti-AMPAR encephalitis developed right after the primary cytoreduction of a patient with HGSOC and retrieved paraneoplastic anti-AMPAR encephalitis cases (n = 66). Gynecologists should pay attention to patients who develop cognitive dysfunction or psychiatric symptoms shortly after the ovarian tumor resection and always include AE in the differentiation diagnosis.

Abstract The recent progress in CuMnAs and Mn3X (X = Sn, Ge, Pt) shows that antiferromagnets (AFMs) provide a promising platform for advanced spintronics device innovations. Most recently, a switchable Fermi‐arc is discovered by the ARPES technique in antiferromagnet NdBi, but the knowledge about electron‐transport property and the manipulability of the magnetic structure in NdBi is still vacant to date. In this study, SdH oscillations are successfully verified from the Dirac surface states (SSs) with 2‐dimensionality and nonzero Berry phase. Particularly, it is observed that the spin‐flop transition only appears when the external magnetical field is applied along [001] direction, and features obvious hysteresis for the first time in NdBi, which provides a powerful handle for adjusting the spin texture in NdBi. Crucially, the DFT shows the Dirac cone and the Fermi arc strongly depend on the high‐order magnetic structure of NdBi and further reveals the orbital magnetic moment of Nd plays a crucial role in fostering the peculiar SSs, leading to unveil the mystery of the band‐splitting effect and to manipulate the electronic transport, high‐effectively, in the thin film works in NdBi. It is believed that this study provides important guidance for the development of new antiferromagnet‐based spintronics devices based on cutting‐edge rare‐earth monopnictides.

Abstract Continuous-variable quantum key distribution (CVQKD) offers the specific advantage of sharing keys remotely by the use of standard telecom components, thereby promoting cost-effective and high-performance metropolitan applications. Nevertheless, the introduction of high-rate spectrum broadening has pushed CVQKD from a single-mode to a continuous-mode region, resulting in the adoption of modern digital signal processing (DSP) technologies to recover quadrature information from continuous-mode quantum states. However, the security proof of DSP involving multi-point processing is a missing step. Here, we propose a generalized method of analyzing continuous-mode state processing by linear DSP via temporal modes theory. The construction of temporal modes is key in reducing the security proof to single-mode scenarios. The proposed practicality oriented security analysis method paves the way for building classical compatible digital CVQKD.

BackgroundAccurate estimation of incidence and prevalence is vital for preventing and controlling diabetes. Administrative data (including insurance data) could be a good source to estimate the incidence of diabetes. However, how to determine the look-back period (LP) to remove cases with preceding records remains a problem for administrative data. A short LP will cause overestimation of incidence, whereas a long LP will limit the usefulness of a database. Therefore, it is necessary to determine the optimal LP length for identifying incident cases in administrative data. ObjectiveThis study aims to offer different methods to identify the optimal LP for diabetes by using medical insurance data from the Chinese population with reference to other diseases in the administrative data. MethodsData from the insurance database of the city of Weifang, China from between January 2016 and December 2020 were used. To identify the incident cases in 2020, we removed prevalent patients with preceding records of diabetes between 2016 and 2019 (ie, a 4-year LP). Using this 4-year LP as a reference, consistency examination indexes (CEIs), including positive predictive values, the κ coefficient, and overestimation rate, were calculated to determine the level of agreement between different LPs and an LP of 4 years (the longest LP). Moreover, we constructed a retrograde survival function, in which survival (ie, incident cases) means not having a preceding record at the given time and the survival time is the difference between the date of the last record in 2020 and the most recent previous record in the LP. Based on the survival outcome and survival time, we established the survival function and survival hazard function. When the survival probability, S(t), remains stable, and survival hazard converges to zero, we obtain the optimal LP. Combined with the results of these two methods, we determined the optimal LP for Chinese diabetes patients. ResultsThe κ agreement was excellent (0.950), with a high positive predictive value (92.2%) and a low overestimation rate (8.4%) after a 2-year LP. As for the retrograde survival function, S(t) dropped rapidly during the first 1-year LP (from 1.00 to 0.11). At a 417-day LP, the hazard function reached approximately zero (ht=0.000459), S(t) remained at 0.10, and at 480 days, the frequency of S(t) did not increase. Combining the two methods, we found that the optimal LP is 2 years for Chinese diabetes patients. ConclusionsThe retrograde survival method and CEIs both showed effectiveness. A 2-year LP should be considered when identifying incident cases of diabetes using insurance data in the Chinese population.

Abstract Endometrial cancer (EC) is the most common female reproductive tract cancer and its incidence has been continuously increasing in recent years. The underlying mechanisms of EC tumorigenesis remain unclear, and efficient target therapies are lacking, for both of which feasible endometrial cancer animal models are essential but currently limited. Here, an organoid and genome editing‐based strategy to generate primary, orthotopic, and driver‐defined ECs in mice is reported. These models faithfully recapitulate the molecular and pathohistological characteristics of human diseases. The authors names these models and similar models for other cancers as organoid‐initiated precision cancer models (OPCMs). Importantly, this approach can conveniently introduce any driver mutation or a combination of driver mutations. Using these models,it is shown that the mutations in Pik3ca and Pik3r1 cooperate with Pten loss to promote endometrial adenocarcinoma in mice. In contrast, the Kras G12D mutati led to endometrial squamous cell carcinoma. Then, tumor organoids are derived from these mouse EC models and performed high‐throughput drug screening and validation. The results reveal distinct vulnerabilities of ECs with different mutations. Taken together, this study develops a multiplexing approach to model EC in mice and demonstrates its value for understanding the pathology of and exploring the potential treatments for this malignancy.

Ovarian cancer is one of the most common reproductive system tumors. The incidence of ovarian cancer in China is on the rise. Poly(ADP-ribose) polymerase (PARP) inhibitor (PARPi) is a DNA repair enzyme associated with DNA damage repair. PARPi takes PARP as a target to kill tumor cells, especially for tumors with homologous recombination (HR) dysfunction. Currently, PARPi has been widely used in clinical practice, mainly for the maintenance of advanced ovarian epithelial cancer. The intrinsic or acquired drug resistance of PARPi has gradually become an important clinical problem with the wide application of PARPi. This review summarizes the mechanisms of PARPi resistance and the current progress on PARPi-based combination strategies.

Abstract Objective Using bipolar disorder (BD) as a control, we explored the possible developmental process of impaired glucose metabolism rhythm. Methods In total, 441 subjects (77, 162, 134, 54, and 14 in the pre-diabetes [pre-DM], DM, BD, BD + pre-DM, and BD + DM groups, respectively) and 160 controls were included. All subjects were assessed using the Neuroticism Extraversion Openness Five-Factor Inventory (NEO-FFI). The hypothalamic-pituitary-adrenal (HPA) and hypothalamic–pituitary–thyroid (HPT) axes were measured. Results Cluster analysis showed that the BD, BD + DM, and DM groups were classified as the ‘disease group, the BD + pre-DM group as the ‘mixed period group’, and the pre-DM group as the ‘pre-disease group’. The conscientiousness factor scores of the NEO-FFI in the ‘disease group’ were higher than the norm but lower than the norm in the ‘pre-disease group’. The scores of neurotic factors in the ‘pre-disease’ and ‘mixed period’ groups were both significantly higher than that in the ‘disease group’ (corrected p

BackgroundClinical rehabilitation for brachial plexus injury is difficult in terms of chronic pain and dysfunction. Physiotherapy is considered a routine intervention for rehabilitation. Common physical therapy may require a variety of instruments. One approach that does not need instruments, but belongs to the field of complementary and alternative medicine, is naprapathy. Naprapathy, also called Tuina in China, has been applied in rehabilitation after brachial plexus injury for a long time. Naprapathy can relieve chronic neuropathic pain, promote local blood circulation, and improve body edema. Naprapathy can passively help improve motor functions in patients with peripheral nerve injury. However, the efficacy of naprapathy in improving rehabilitation after brachial plexus injury is unclear. ObjectiveThis study aims to evaluate the additional value of naprapathy when combined with conventional physical therapy for the treatment of brachial plexus injury. MethodsThis will be a single-center randomized controlled trial. A total of 116 eligible patients with brachial plexus injury will be randomly divided into an experimental group (naprapathy plus physical therapy group) or a control group (physical therapy group). The participants will be followed up for 4 weeks of treatment. Observation outcomes will include the visual analog scale score, upper limb index, electromyography findings, and adverse reactions, among others. The measuring points for outcomes will be the baseline and the completion of treatment. In addition, a quality control group independent from the research team will be set up to control the quality of the trial. Finally, the data will be analyzed using SPSS software (version 21.0; IBM Corp). ResultsThe study is recruiting participants. The first participant was enrolled in September 2021. As of January 2023, a total of 100 participants have been enrolled. The trial is expected to be completed by September 2023. The study protocol was approved by the Ethics Review Committee of Yue Yang Hospital affiliated with the Shanghai University of Traditional Chinese Medicine (2021-012). ConclusionsOne limitation of this trial is that we will be unable to achieve strict double-blinding because of the features of naprapathy. The trial aims to contribute reliable evidence for decision-making in naprapathy for treating brachial plexus injury. Trial RegistrationChinese Clinical Trial Registry ChiCTR2100043515; http://www.chictr.org.cn/showproj.aspx?proj=122154 International Registered Report Identifier (IRRID)DERR1-10.2196/46054

PurposeThe aim of this study was to explore the value of the homeostasis model assessment of IR (HOMA-IR) as a judgment criterion for metformin pre-treatment before in vitro fertilization/intracellular sperm injection (IVF/ICSI) and embryo transfer (ET) for polycystic ovarian syndrome (PCOS) patients.Materials and methodsThe clinical and laboratory information of PCOS patients who received IVF/ICSI-ET from January 2017 to September 2021 was retrospectively analyzed. We compared the clinical pregnancy rate (primary outcome) and controlled ovarian stimulation (COS)-related parameters (secondary outcomes) between patients with and without metformin pre-treatment for all PCOS patients not grouped by HOMA-IR, PCOS patients with HOMA-IR < 2.71, and PCOS patients with HOMA-IR ≥ 2.71.ResultsA total of 969 PCOS patients who received the GnRH-antagonist protocol were included in this study. For all PCOS patients, the metformin group showed comparable clinical pregnancy rates in fresh ET cycles and frozen ET cycles compared with the control group (55.9% vs. 57.1%, p = 0.821 and 63.8% vs. 60.9%, p = 0.497). For PCOS patients with HOMA-IR < 2.71, the clinical pregnancy rates in both fresh ET cycles and frozen ET cycles were statistically similar between the two groups (61.5% vs. 57.6%, p = 0.658 and 70.6% vs. 66.7%, p = 0.535). For PCOS patients with HOMA-IR ≥ 2.71, the clinical pregnancy rate in fresh ET cycles was comparable between the two groups (51.5% vs. 56.3, p = 0.590), but it was statistically higher in the metformin group than in the control group in frozen ET cycles (57.1% vs. 40.0%, p = 0.023). The metformin group had less oocytes retrieved, a lower cleaved oocyte rate, a lower available D3 embryo rate, a lower blastocyst formation rate, and a lower available blastocyst rate than the control group.ConclusionHOMA-IR is a judgment criterion for metformin pre-treatment before IVF/ICSI-ET in patients with PCOS. Metformin pre-treatment could be added for PCOS patients with HOMA-IR ≥ 2.71 during frozen IVF/ICSI-ET cycles to improve the clinical pregnancy rate.

The family of poly (ADP-ribose) polymerases (PARPs) consists of 17 members, which have been demonstrated as having effects on a series of cellular processes, including DNA replication and repair. PARP inhibitors (PARPi) suppress DNA repair through “PARP trapping”, thus, constitute an important treatment option for cancer nowadays. In addition, PARP inhibition and homologous recombination repair (HRR) defects are synthetically lethal, giving a promising therapeutic for homologous recombination repair deficient (HRD) tumors including BRCA mutation. However, overlapping hematologic toxicity causes PARPi to fail in combination with some first-line chemotherapies. Furthermore, recent literature has demonstrated that PARP1 inhibition and PARP1-DNA trapping are key for antitumor activity in HRD cancer models. Currently approved PARPi have shown varying levels of selectivity for the entire 17-member PARP family, hence contribute to toxicity. Together, these findings above have provided the necessity and feasibility of developing next-generation PARPi with improved selectivity for PARP1, expanding significant clinical values and wide application prospects both in monotherapy and combination with other anticancer agents. In this review, we summery the latest research of current approved PARPi, discuss the current status and future promise of next-generation PARP1-selective inhibitor AZD5305, including its reported progress up to now and anticipated impact on clinical.

Gut microbiota dysbiosis promotes metabolic syndromes (e.g., hypertension); however, the patterns that drive hypertensive pathology and could be targeted for therapeutic intervention are unclear. We hypothesized that gut microbes might translocate to the kidney to trigger hypertension. We aimed to uncover their method of colonization, and thereby how to maintain blood pressure homeostasis. Using combined approaches based on fluorescence in situ hybridization (FISH) and immunofluorescence staining, electron microscopy analysis, bacterial cultures, species identification, and RNA-sequencing-based meta-transcriptomics, we first demonstrated the presence of bacteria within the kidney of spontaneously hypertensive rats (SHRs) and its normotensive counterpart, Wistar-Kyoto rats (WKYs), and patients with hypertension. Translocated renal bacteria were coated with secretory IgA (sIgA) or remained dormant in the L-form. Klebsiella pneumoniae (K.pn) was identified in the kidneys of germ-free (GF) mice following intestinal transplantation, which suggested an influx of gut bacteria into the kidneys. Renal bacterial taxa and their function are associated with hypertension. Hypertensive hosts showed increased richness in the pathobionts of their kidneys, which were partly derived from the gastrointestinal tract. We also demonstrated the indispensable role of bacterial IgA proteases in the translocation of live microbes. Furthermore, Tartary buckwheat dietary intervention reduced blood pressure and modulated the core renal flora-host ecosystem to near-normal states. Taken together, the unique patterns of viable and dormant bacteria in the kidney provide insight into the pathogenesis of non-communicable chronic diseases and cardiometabolic diseases (e.g., hypertension), and may lead to potential novel microbiota-targeted dietary therapies.

BackgroundClinically, few patients with locally advanced cervical cancer (LACC) are insensitive to neoadjuvant chemotherapy (NACT). Recent studies have reported that circulating microRNAs (miRNAs) may be involved in the response to NACT. The aim of this study was to discover the potential miRNAs that can predict the response to NACT in LACC.MethodsPair-matched blood samples of 39 LACC patients before and after receiving NACT were collected. Seven paired samples were used for microRNA microarray analysis. Targeted miRNAs were selected by bioinformatics analysis and were validated by quantitative reverse transcription–polymerase chain reaction (qRT-PCR). All 39 patients were assigned into either the responders group or the non-responders group after NACT. The predictive performance of selected microRNA was evaluated by sensitivity, specificity, accuracy, and the area under the receiver operating characteristic (ROC) curve.ResultsA total of 17 miRNAs downregulated before NACT and upregulated after NACT were selected according to microarray analysis in our previous study, and miR-326 and miR-376a-3p were selected for further exploration. According to the responses and the evaluation criteria, 25 patients reached partial response (PR) and 14 patients remained stable. Further qRT-PCR analysis showed that miR-326 significantly downregulated before NACT and upregulated after NACT in 12 responders (p = 0.02). The expression of miR-376a-3p showed no statistical difference before and after NACT in these 12 responders. Then, miR-326 provided an AUC-ROC of 0.75 (p = 0.04) in the discrimination between the responders and non-responders groups. The cutoff value of ROC for miR-326 to predict the response of NACT was

Men should not be overlooked in research on human papillomavirus (HPV) and its associated genital diseases. This is because men infected with HPV are not only at higher risk of genital cancers, but also increase their partners’ risk of HPV infection and reinfection through sexual contact. Herein, we summarized the state of knowledge regarding the prevention and treatment of HPV infection in men as well as the possible effects of the prevention and treatment of HPV in men on their female partners. Condom use, smoking cessation, male circumcision, and HPV vaccination for men each play an important role in preventing HPV infection within heterosexual couples. Additionally, men could choose to test for certain types of HPV, such as the oncogenic HPV16 or HPV18 strains, as part of a routine screening program when their partner is positive for HPV. Although there is no recognized treatment for HPV infection as of yet, immunotherapy drugs, such as toll-like receptor agonists, therapeutic HPV vaccines, and immune checkpoint inhibitors, have shown promising results in clinical trials and in actual clinical practice. HPV infection in men also increases the risk of cervical cancer in their female partners. Because of the high partner concordance for HPV demonstrated in prior research, the prevention and treatment of HPV in men should be explored more comprehensively in future research.

ObjectiveTo establish nomograms to predict the risk of postoperative complications following cytoreductive surgery in patients with advanced epithelial ovarian cancer (AEOC).MethodsA multicenter retrospective cohort study that included patients with FIGO stage IIIC-IV epithelial ovarian cancer who underwent cytoreductive surgery was designed. By using univariate and multivariate analyses, patient preoperative characteristics were used to predict the risk of postoperative complications. Multivariate modeling was used to develop Nomograms.ResultsOverall, 585 AEOC patients were included for analysis (training cohort = 426, extrapolation cohort = 159). According to the findings, the training cohort observed an incidence of postoperative overall and severe complications of 28.87% and 6.10%, respectively. Modified frailty index (mFI) (OR 1.96 and 2.18), FIGO stage (OR 2.31 and 3.22), and Surgical Complexity Score (SCS) (OR 1.16 and 1.23) were the clinical factors that were most substantially associated to the incidence of overall and severe complications, respectively. The resulting nomograms demonstrated great internal discrimination, good consistency, and stable calibration, with C-index of 0.74 and 0.78 for overall and severe complications prediction, respectively. A satisfactory external discrimination was also indicated by the extrapolation cohort, with the C-index for predicting overall and severe complications being 0.92 and 0.91, respectively.ConclusionsThe risk of considerable postoperative morbidity exists after cytoreductive surgery for AEOC. These two nomograms with good discrimination and calibration might be useful to guide clinical decision-making and help doctors assess the probability of postoperative complications for AEOC patients.

Neuroendocrine carcinoma of the cervix (NECC) is a highly aggressive and rare gynecological malignancy with a poor prognosis. Despite aggressive local and systemic treatments, there are high rates of locoregional recurrence and distant metastases. Therefore, more potent treatments are required to manage NECC. In recent years, emerging immune checkpoint inhibitors, such as programmed cell death protein 1 (PD-1)/programmed cell death ligand 1 (PD-L1) inhibitors, have been used in treating various solid tumors and provide a new direction for immune-targeted therapy for NECC. In this review, we summarize the biomarkers useful for the evaluation of the therapy with PD-1/PD-L1 inhibitors in patients with NECC and the clinical applications and prospects of monotherapy with PD-1/PD-L1 inhibitors and combinations with other therapies in patients with NECC. In some individual case reports, therapeutic strategies with PD-1/PD-L1 inhibitors showed good efficacy. Further studies are needed to confirm the possibility of using PD-1/PD-L1 inhibitors as a standard treatment strategy in NECC.

BackgroundFrailty has been related with poor prognosis of various diseases, including ovarian cancer. We performed a systematic review and meta-analysis to evaluate the association between frailty and long-term survival of patients with ovarian cancer.MethodsRelevant cohort studies were retrieved by search of PubMed, Embase, Cochrane’s Library, and Web of Science electronic databases. Two authors independently performed literature search, data collection, and statistical analyses. A random-effect model incorporating the possible influence of heterogeneity was used to pool the results.ResultsNine cohort studies including 2497 women with confirmed diagnosis of ovarian cancer contributed to the meta-analysis, and 536 (21.5%) of them were with high frailty. The median follow-up durations varied between 24 and 69 months. Compared to patients with low or non-frailty, OC patients with high frailty were associated with poor overall survival (risk ratio [RR]: 1.61, 95% confidence interval [CI]: 1.41 to 1.85, p < 0.001; I2 = 0%) and progression-free survival (RR: 1.51, 95% CI: 1.20 to 1.89, p < 0.001; I2 = 0%). Subgroup analyses according to study design, cancer stage, age of patients, scales for frailty evaluation, follow-up duration, and quality score of the included study showed consistent association between high frailty and poor overall survival in women with ovarian cancer (p for subgroup effects all < 0.05). After considering GRADE criteria for strength of the evidence, it was rated low for both the two outcomes.ConclusionHigh frailty may be an independent risk factor of poor survival in women with ovarian cancer. Evaluating frailty may be important for predicting the prognosis and determining the optimal anticancer treatments in women with ovarian cancer.Systematic Review Registrationhttps://inplasy.com/, identifier INPLASY202290028.

Underwater spherical robots are good assistants for ocean exploration, where motion control algorithms play a vital role. Conventional motion control algorithms cannot eliminate the coupling relationship between various motion directions, which will cause the motion control of various directions to interfere with one other and significantly affect the control effect. This study proposes a new decoupling motion control algorithm based on the robot attitude calculation for an underwater spherical robot designed for offshore, shallow water, and narrow terrain. The proposed method uses four fuzzy proportional–integral–derivative (PID) controllers to independently control the robot’s movement in all directions. Experiments show that the motion control algorithm proposed in this study can significantly improve the flexibility and accuracy of the movement of underwater spherical robots.

ObjectiveTo study the correlation between BRCA mutation status and the risk of adverse reactions in patients with ovarian cancer.MethodA real-world study was conducted at the largest gynecological oncology center in western China, the West China Second University Hospital of Sichuan University. The research subjects were patients diagnosed with ovarian cancer who were initially treated in our hospital from January 2016 to January 2020 and had their BRCA gene status evaluated. Multivariate Cox analysis was conducted to investigate the correlation between the BRCA mutation status and adverse reactions in ovarian cancer patients during initial treatment.ResultsA total of 349 ovarian cancer patients were enrolled, including 79 patients with pathogenic BRCA variants, resulting in a pathogenic mutation rate of 22.6%. Among these 79 patients, 57 had BRCA1 variants and 22 had BRCA2 variants, yielding a pathogenic mutation rate of 16.3% and 6.3%, respectively. Multivariate COX analysis revealed that pathogenic BRCA variants were not related to the risk of adverse reactions, such as myelosuppression and allergies to chemotherapy drugs (P>0.05), during the initial treatment of ovarian cancer.ConclusionBRCA variants did not increase the risk of adverse reactions, such as myelosuppression and allergies to chemotherapy drugs, in ovarian cancer patients during initial treatment.

The generation of α-carbon radicals from alkoxyl radicals is challenging because 1,2-hydrogen atom transfer (HAT) is usually less favoured than 1,5-HAT. Here, the authors report a strategy to inhibit 1,5-HAT by introducing a silyl group into the α-position of alkoxyl radicals, enabling preparation of α-alkoxylimino alcohols and α-heteroaryl alcohols.

The Proactive Molecular Risk Classifier for Endometrial Cancer (ProMisE) is a molecular classification system that identifies endometrial cancer (EC) into four prognostically distinct subtypes: POLE-mutated, mismatch repair deficiency (MMR-D), p53 wild-type (p53wt), and p53 abnormal (p53abn). However, few reports have applied the ProMisE classifier to EC patients who underwent fertility-preserving treatment (FPT) so far. This study evaluated whether the ProMisE classifier predicted in early-stage EC patients after FPT. We first summarized the three reported outcomes of ProMisE applied to EC patients who received FPT. The hormone-treated patients with EC from 2010 to 2020 in our facility were then analyzed. By sequential immunohistochemistry and Sanger sequencing of POLE according to the ProMisE system, formalin-fixed paraffin-embedded blocks of patients before treatment were collected and classified into POLE-mutated, MMR-D, p53wt, and p53abn subtypes. The primary outcome was a complete response rate after FPT. Thirteen patients were enrolled from our facility, with 3 (3/13) MMR-D, 0 (0/13) POLE, 8 (8/13) p53wt, 1 (1/13) p53abn, and 1 (1/13) failed with DNA amplification. Six (6/8) patients with p53wt, 2 (2/3) patients with MMR-D, and 1 (1/1) patient with p53abn achieved a complete response in 6 months after treatment. The results of our study and the reported outcomes were finally combined. A total of 106 patients who underwent FPT were included. Of these, 23 (21.7%) were classified as MMR-D, 3 (2.8%) as POLE-mutated, 3 (2.8%) as p53abn, and 77 (72.6%) as p53wt. There was no significant difference in the complete response rate (P = 0.152) and recurrence rate (P = 0.174) between MMR-D and p53wt subtypes after FPT. Based on current data, we observed no prognostic significance of the ProMisE classifier in EC patients who underwent FPT. Larger prospective studies are needed to elucidate the precise prognostic meaning of this molecular classifier in these cases.

BackgroundDebulking cytoreduction surgery with bowel resection is a common intervention for ovarian cancer. It is controversial whether ostomy causes worse survival outcomes and how clinical physicians should choose which patients to undergo ostomy. During this study, we performed a systematic review to determine whether ostomy leads to worse outcomes after bowel resection compared to anastomosis. We also summarized the possible indications for ostomy. MethodsWe searched PubMed, Embase, and Cochrane for articles containing the phrase “ovarian cancer with bowel resection” that were published between 2016 and 2021. We included studies that compared primary anastomosis with ostomy. We mainly focused on differences in the anastomotic leakage rate, length of hospital stay, overall survival, and other survival outcomes associated with the two procedures.Results and ConclusionOf the 763 studies, three were ultimately included in the systematic review (N=1411). We found that ostomy did not contribute to worse survival outcomes, and that the stoma-related complications were acceptable. Indications for ostomy require further study. Bowel resection segment margins and the distance from the anastomosis to the anal verge require consideration.

ObjectiveThis study evaluated the oncologic outcomes of laparoscopy and laparotomy in the management of early-stage ovarian cancer patients.MethodsWe conducted an observational study of women diagnosed with International Federation of Gynecology and Obstetrics (FIGO) 2014 stage I ovarian cancer who underwent surgery at the West China Second University Hospital from 2012 to 2020. Patients who received adjuvant chemotherapy before surgery, those with non-epithelial histopathological types, or those with insufficient data were excluded. Using propensity score matching, data from consecutive laparoscopic patients treated by laparoscopy were matched 1:2 with a cohort of patients undergoing open surgery. The operative and survival outcomes among the matched cohorts were examined using the Kaplan–Meier method.ResultsAmong 200 eligible patients, 74 patients undergoing laparoscopy were compared with a cohort of 126 patients undergoing open surgery. Baseline characteristics were similar between groups after matching. Patients who had laparoscopy had a shorter operative time (P = 0.001), a shorter hospital stay (P

Abstract Background The 2018 International Federation of Gynecology and Obstetrics (FIGO) staging guideline for cervical cancer includes stage IIIC recognized by preoperative radiology (IIIC-r) to state there are lymph nodes metastases (LNM) identified by imaging tools. We aim to explore the reasonability and limitations of stage IIIC-r and try to explore the potential reasons. Methods Electronic medical records were used to identify patients with cervical cancer. According to the new staging guidelines, patients were reclassified and assigned into five cohorts: stage I, stage II, stage IIIC-r, LNM confirmed by pathology (IIIC-p) and LNM detected by radiology and confirmed by pathology (IIIC r + p). Five-year overall survivals were estimated for each cohort. The diagnosis accuracy of computed tomography (CT), magnetic resonance imaging (MRI) and diameter of detected lymph nodes were also evaluated. Results A total of 619 patients were identified. The mean follow-up months were 65 months (95% CI 64.43–65.77) for all patients. By comparison, the 5-year overall survival rates were not statistically different (p = 0.21) among stage IIIC-r, stage I and stage II. While, the rates were both statistical different (p

Abstract This updated meta-analysis sought to explore whether pretreatment neutrophil-to-lymphocyte ratio (NLR) could serve as an independent predictor for survival outcomes in patients with cervical cancer. We searched PubMed, Embase, Web of science and Scopus for studies on the association of pretreatment serum NLR with overall survival (OS) and progression-free survival (PFS) among patients with cervical cancer. Included studies with a hazard ratio (HR) and 95% confidence interval (CI) or a p-value were weighted by generic inverse-variance and pooled in a random effects meta-analysis. Subgroup analyses were conducted according to regions, NLR cut-off values and treatments. Publication bias was analyzed by Egger’s and Begg’s tests. A total of 14 studies comprising 6041 patients were included. The median cut-off value for NLR was 2.46 (range from 1.60 to 3.80). The higher NLR was associated to worse OS (HR 1.86, 95% CI 1.44–2.40) and PFS (HR 1.67, 95% CI 1.25–2.23), compared with lower NLR. This association still exited when analyzed according to regions, NLR cut-off values. Moreover, Significant association between NLR and OS was observed in studies which included patients with early stage disease and receiving radical surgeries. High NLR is independently associated with decreased OS and PFS in patients with cervical cancer. Pretreatment NLR is of independent value to predict the survival outcomes in patients with cervical cancer, regardless of regions and primary treatments.

ObjectivesTo vertically analyze the trend of surgical approaches, demographics, surgical morbidity, and long-term survival outcomes of early-stage cervical cancer over the past 11 years and to determine whether there have been any significant changes.MethodsA total of 851 patients with consecutive International Federation of Gynecology and Obstetrics (FIGO) 2009 stage IA–IIA cervical cancer diagnosed between January 2008 and June 2018 at a single center in China were included in this retrospective study. Trends in the rate of minimally invasive surgery (MIS), demographics, surgical morbidities, and long-term survival outcomes were determined. We categorized patients into two groups according to their year of operation. The demographics, pathological factors, surgical morbidity, and long-term survival outcomes were compared between these two groups.ResultsRegarding the surgical approach, there was a significant increase in the rate of laparoscopic radical hysterectomy (LRH) performed over the study period, from 7.8% in 2008 to 72.5% in 2018 (p < 0.0001). The mean age of patients who underwent abdominal radical hysterectomy (ARH) has increased slightly from 2008 to 2018, and those who underwent ARH in the second half of the study period (2014–2018) were significantly older (45.01 vs. 47.50 years; p = 0.001). The most impressive changes over the past 11 years have occurred in the surgical morbidity in both the ARH and LRH groups. The overall surgical morbidity decreased from 29.2% in 2008 to 11.9% in 2018, with an annual rate of 1.57%. The median estimated blood loss volume of the ARH group was 500 ml (range 50–2,000) in the first few years compared to 400 ml (30–2500) in the last few years of the study period (p < 0.0001), which in the LRH group was 350 ml (range 150–800) and 150 ml (range 5–1,000), respectively (p < 0.0001). Similarly, allogeneic blood transfusions and hospital stay have all decreased dramatically over time in both approaches. On the other hand, our study did not reveal any significant statistical changes in long-term survival outcomes over the follow-up period in either group.ConclusionsThe findings of our study demonstrate that great progress in surgically managed cervical cancer has been made over the last decade in West China. Our retrospective study demonstrated that the year of operation does not appear to influence the long-term survival, but the surgical morbidity impressively decreased over the study period in both the ARH and LRH groups, which reflects that the higher hospital surgical volume for radical hysterectomy (RH) was not associated with lower survival outcomes but related to the reduction of surgical morbidity.

The distribution line network is the electric power infrastructure directly facing the users, with the characteristics of large coverage and complex network, and its operation safety is directly related to the stability and reliability of the power supply system, which is the key link to ensure the safety of power supply and the reliability of residential electricity consumption. In order to realize the autonomous obstacle avoidance and autonomous navigation of the live working manipulator for inspection and maintenance of the power grid equipment, a mobile manipulator intelligent control method combining SumTree-weighted sampling and deep deterministic policy gradient (DDPG) is proposed. Firstly, the traditional DDPG algorithm is improved to optimize the action value function of Q-learning to get a better control strategy, and the weighted sampling technique is used to add priority to each sample in the replay buffer, which improves the learning speed and accelerates the convergence speed. The corresponding environmental state space is designed, and simulation experiments are conducted to verify the proposed manipulator control method. Simulation results demonstrate that the proposed method performs better than traditional DDPG and DQN methods in obstacle avoidance and navigation tasks, with faster convergence, better path planning ability, and lower offset cost, which can provide theoretical and technical references for realizing fully autonomous power grid inspection operations.

Abstract Background To evaluate the effect of clinicopathologic factors on the prognosis and fertility outcomes of BOT patients. Methods We performed a retrospective analysis of BOT patients who underwent surgical procedures in West China Second University Hospital from 2008 to 2015. The DFS outcomes, potential prognostic factors and fertility outcomes were evaluated. Results Four hundred forty-eight patients were included; 52 recurrences were observed. Ninety-two patients undergoing FSS achieved pregnancy. No significant differences in fertility outcomes were found between the staging and unstaged surgery groups. Staging surgery was not an independent prognostic factor for DFS. Laparoscopy resulted in better prognosis than laparotomy in patients with stage I tumours and a desire for fertility preservation. Conclusion Patients with BOT fail to benefit from surgical staging. Laparoscopy is recommended for patients with stage I disease who desire to preserve fertility. Physicians should pay more attention to risk of recurrence in patients who want to preserve fertility.

Methods for direct incorporation of tri- and di-fluoroethanol units in molecules are relatively limited. Here, the authors report two organosilicon reagents which are applied to allylation, alkylation and alkenylation reactions as tri- and di-fluoroethanol transfer reagents.

This study aimed to investigate the effect of Fyn gene silencing on the apoptosis of oligodendrocytes (OLs) in epileptic model in vitro and the involved mechanism. Primary oligodendrocyte pro-genitor cells (OPCs) were separated from rats and differentiated to OLs. Immunofluorescent labeling showed positive expression of A2B5 in OPCs and Olig2 in OLs, suggesting the successful separation of OPCs and OLs. Three Fyn siRNAs (si-Fyn) and Fyn siRNA negative control (NC) were transfected into OLs. Western blot showed that among three si-Fyn groups, si-Fyn3 caused the lowest Fyn expression, so si-Fyn3 was chosen for following experiment. Cells were divided into four groups: Control, Model, NC and si-Fyn. In the Model group, cells were cultured in Mg-free extracellular fluid for 3 h. The morphology of control cells was normal. However, the migration of neurons, the aggregation of cell bodies and the “grid-like” changes of neural networks were observed in the model cells. OLs apoptosis in various groups was assessed by flow cytometry. Expression of Fyn, ERK1/2 and phosphorylated ERK1/2 (p-ERK1/2) in OLs of various groups was evaluated by western blot. Compared with the Control group, the apoptotic rates, the Fyn expression and p-ERK1/2/ERK1/2 ratio in the Model and NC groups increased significantly (p

While traditional Chinese medicine has displayed a positive and effective role in saving lives of COVID-19 patients, Tuina, which is an important component in Chinese medicine, has also shown its merits in enhancing the immune function and relieving symptoms in COVID-19 patients. This article elaborates the long history of Tuina in treating and preventing epidemic diseases and its effect in improving the immune function. It also introduces some special Tuina methods, for instance, sputum drainage by the back-patting method to enable the discharge of sputum; slant-scrubbing method applied on the hypochondriac regions to bring the effect of soothing the liver to regulate qi, which may also relieve anxiety of patients with COVID-19; and spine-pinching method to enhance human resistance to diseases, which is more suitable for the elderly and for children with mild or common types of COVID-19 and can also be used for health care and disease prevention among the general population. Tuina methods for children using the common children's specific Tuina points and manipulations to improve children's body constitution are also mentioned in the article. Self-acupoint Tuina for health care, including acupoints for prevention purposes, acupoints for early clinical stage (mild stage) and recovery stage, as well as acupoints for children health care and specific operations, is also illustrated in the article. Moreover, basic exercises for health care, such as eight-section brocade, Shaolin internal exercises, six-character formula, and change of tendons, are also presented. In the final analysis, this article is aimed at some ideas and feasible applications of Tuina therapy in the prevention and treatment of COVID-19, in the hope to provide some worthy experience and introduce methods in preventing and fighting against COVID-19 to people all over the world.

PurposeTo compare the clinical outcomes of patients with early-stage cervical cancer who underwent minimally invasive surgery (MIS) by surgeons in different phases and evaluate whether the proficiency of surgeons affects the survival outcomes.Materials and MethodsA total of 851 patients with early-stage cervical cancer who underwent radical hysterectomy between January 2008 and June 2018 (every year from January to June) at a tertiary hospital were retrospectively analyzed. We categorized patients into four phases according to their sequence (phase one, 1-10 cases; phase two: 11-20 cases; phase three: 21-30 cases; phase four: > 30 cases). Demographics and clinical and pathological data were collected and analyzed.ResultsThere were no statistical differences between the open surgery and MIS groups regarding three- and five-year overall survival (OS) and disease-free survival (DFS). The OS and DFS of patients in the MIS group in phase one were significantly lower than those in later phases and those in the open surgery group after adjustment (OS, P = 0.009; HR, 2.896; 95%CI, 1.303-6.435; DFS, P = 0.009; HR, 2.712; 95%CI, 1.289-5.706). Survival outcomes were not statistically significant when comparing different surgeons.ConclusionThe phase one cases of MIS had lower OS and DFS than those in later phases and those in the open surgery group. Thus, we suggest that the proficiency of surgeons is associated with survival outcomes of MIS. Favorable outcomes can be obtained after a certain number of MIS cases.

Poly ADP-ribose polymerase inhibitor (PARPi) has become an important maintenance therapy for ovarian cancer after surgery and cytotoxic chemotherapy, which has changed the disease management model of ovarian cancer, greatly decreased the risk of recurrence, and made the prognosis of ovarian cancer better to certain extent. The three PARPis currently approved by the United States Food and Drug Administration (FDA) and the European Medicines Agency (EMA) for the treatment of ovarian cancer are Olaparib, Niraparib and Rucaparib. With the incremental results from new clinical trials, the applicable population of PARPi for ovarian cancer have expanded to population with non-BRCA mutations. Although BRCA mutated population are still the main beneficiaries of PARPi, recent clinical trials indicated PARPis’ therapeutic potential in non-BRCA mutated population, especially in homologous recombination repair deficiency (HRD) positive population. However, lack of unified HRD status detection method poses a challenge for the accurate selection of PARPi beneficiaries. The reversal of homologous recombination (HR) function during the treatment will not only cause resistance to PARPis, but also reduce the accuracy of the current method to determine HRD status. Therefore, the development of reliable HRD status detection methods to determine the beneficiary population, as well as rational combination treatment are warranted. This review mainly summarizes the latest clinical trial results and combination treatment of PARPis in ovarian cancer with non-BRCA mutations, and discusses the application prospects, including optimizing combination therapy against drug resistance, developing unified and accurate HRD status detection methods for patient selection and stratification. This review further poses an interesting topic: the efficacy and safety in patients retreated with PARPis after previous PARPi treatment---“PARPi after PARPi”.

The most advanced epithelial ovarian cancer develops recurrent disease despite maximal surgical cytoreduction and adjuvant platinum-based chemotherapy. Treatment with secondary cytoreductive surgery (SCS) combined with chemotherapy or with chemotherapy alone for patients with platinum-sensitive recurrent ovarian cancer (ROC) is currently under heated discussion. Encouragingly, the results of the AGO DESKTOP III Study and the SOC1/SGOG-OV2 trial, which have been published recently, showed a striking advantage in terms of overall survival (OS) and progression-free survival (PFS) of ROC patients undergoing SCS compared to chemotherapy alone; moreover, a benefit of SCS exclusively for patients with complete gross resection (CGR) was particularly highlighted. CGR is considered the ultimate goal of SCS, on condition that the balance between maximal survival gain and minimal operative morbidity is maintained. Several models have been proposed to predict the rate of CGR, such as the MSK criteria, the AGO score, and the Tian model, over the last 15 years. This summary is mainly about the several previously published prediction models for CGR in SCS of ROC patients and discusses the effectiveness and limitations of these prediction models.

This study aimed to comprehensively assess the value of Dienogest (DNG) as a maintenance treatment following conservative surgery for endometriosis in terms of the outcomes of disease and pregnancy. We searched for relevant studies and trials up to November 2020 from PubMed, Cochrane Library, Medline, and EMBASE databases as well as the Web of Science. Patients who received DNG maintenance treatment were compared to those who received other treatments (OT), including the levonorgestrel-releasing intrauterine system (LNG-IUS) and gonadotropin-releasing hormone analogs (GnRH-a), or non-treatment (NT). The primary outcomes were disease recurrence and pregnancy rates. Eleven studies were included in this meta-analysis. The pooled analysis indicated that DNG maintenance treatment was associated with a lower rate of disease recurrence. A significant difference was observed in DNG maintenance treatment compared with NT, but not with OT, in the pregnancy rates postoperatively. Moreover, DNG maintenance treatment was related to a significant increase in vaginal bleeding and weight gain. DNG can be recommended as a maintenance treatment for patients with endometriosis to decrease the rates of disease recurrence following conservative surgery. However, DNG maintenance treatment has no advantage in improving pregnancy rates compared to OT.

Abstract Background The clinical behaviors and cytogenetics of solitary uterine leiomyomas (SUL) and multiple uterine leiomyomas (MUL) vary, which greatly affects the choice of treatments for reproductive-aged patients with leiomyomas. Our previous study demonstrated that a series of microRNAs, including miR-146b-5p, are dysregulated and play important roles in the development of SUL and MUL. Long non-coding RNAs (lncRNAs) can participate in the pathogenesis of several diseases by regulating the expression of microRNAs; however, their roles in regulating miR-146b-5b and in the pathology of leiomyomas are unclear. Methods Pair-matched uterine leiomyoma and adjacent normal myometrium tissue samples were collected from 37 patients with leiomyomas, including 15 with SUL and 22 with MUL. Six paired samples (three SUL and three MUL samples) were used for lncRNAs microarray analysis. Targeted lncRNAs were selected by bioinformatics analysis, and were verified by quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and a dual-luciferase reporter assay. Growth curve analysis and qRT-PCR were used to evaluate the effect of silencing the lncRNA lnc-AL445665.1–4 on cell proliferation and miR-146b-5p expression, respectively. Results There were 245 up-regulated and 243 down-regulated lncRNAs in SUL, and 119 up-regulated and 447 down-regulated lncRNAs in MUL. Fifty-five of the selected lncRNAs were predicted to target miR-146b-5p, which is up-regulated in SUL and down-regulated in MUL. Four lncRNAs were selected after Venn diagram analysis showing common dysregulation in the three groups. Lnc-AL445665.1–4 was selected for further exploration. qRT-PCR showed that lnc-AL445665.1–4 expression was significantly up-regulated in MUL compared with SUL in an additional 12 and 19 paired SUL-normal and MUL-normal samples, respectively. The dual-luciferase reporter assay demonstrated the presence of binding sites on lnc-AL445665.1 for miR-146b-5p. Silencing lnc-AL445665.1–4 not only inhibited cell proliferation but also negatively regulated the expression of miR-146b-5p. Conclusions Our results suggest that lnc-AL445665.1–4 may be involved in the development of MUL by interacting with miR-146b-5p. Further investigation of the roles of lncRNAs and miRNAs may help to optimize the clinical management of leiomyoma patients. Lnc-AL445665.1–4 could be a novel target for genetic therapy or serve as a biomarker for predicting the recurrence of MUL in patients that have undergone myomectomy.

Abstract Background Several previous studies have confirmed that thrombocytosis was related to reduced survival in many solid tumors. However, the prognostic significance of thrombocytosis in endometrial carcinoma (EC) was still controversy. Therefore, we conducted this study to assess the prognostic value of thrombocytosis in EC. Methods The database including PubMed, MEDLINE, EMBASE, and Web of Science was searched to explore available literature. Above all, the hazard ratio (HR), odds ratios (OR) with 95% confidence intervals (CIs) was used to investigate the correlation between thrombocytosis and overall survival (OS) and disease-free survival (DFS). Moreover, the association between thrombocytosis and patient clinicopathological characteristics was explored. Publication bias and sensitivity analysis also were conducted in this study. Results Overall, 11 studies involving 3439 patients were contained in this study. The results revealed that pretreatment thrombocytosis was significantly related to a decreased OS (pooled HR = 2.99; 95% CI = 2.35–3.8; P

IntroductionUterine leiomyoma (UL) is a common benign pelvic tumor in women that has a high recurrence rate. Our aim is to propose a prognostic index (PI) model for predicting the long-term recurrence risk of uterine leiomyoma (UL).MethodsA total of 725 women who underwent myomectomy were enrolled in this retrospective multicenter study. Patients were contacted for follow-up. A PI model was proposed based on the multivariate Cox regression analysis in the model group. The predictive value of this model was tested in both internal and external validation group.ResultsPI formula = 1.5(if 3-5 leiomyomas) or 2(if >5 leiomyomas)+1(if residue)+1(if not submucosal)+1(if combined endometriosis). The PI value was divided into low-risk, intermediate-risk, and high-risk group by cut-off values 1.25 and 3.75. In the model group, the high-risk group had a significantly 4.55 times greater recurrence risk of UL than that in the low-risk group [cumulative recurrence rate (CR): 82.1% vs 29.5%, HR = 4.55, 95% CI 2.821-7.339]; the intermediate-risk group had a significantly 2.81 times greater recurrence risk of UL than that in the low-risk group (CR: 62.3% vs 29.5%, HR = 2.81, 95% CI 2.035-3.878). The differences between any two risk groups were also significant (P< 0.05) in both internal and external validation groups.ConclusionThe model was proved to be effective in predicting recurrence of UL after myomectomy.

PurposeTo analyze the potential prognostic factors of epithelial ovarian cancer (EOC) in women aged under 35 compared to those aged 60–79.MethodsCases were retrospectively obtained from SEER database. Clinical characteristics, such as race, histological type, AJCC stage, laterality of tumors, CA125 results, and surgical strategies, were analyzed in < 35 years group and 60–79 years group. Kaplan-Meier survival curves were used to evaluate overall survival (OS) and cause-specific survival (CSS). Cox proportional hazard model was used to identify the predictors for CSS.ResultsSixteen thousand eight hundred forty-seven EOC patients diagnosed in 2004–2015 were identified from SEER database, with 1,015 aged under 35 and 15,833 aged 60–79. In < 35 years group, mucinous (32.2%) was the most common histological type, followed by high-grade serous (26.6%) and endometrioid (18.3%), while in 60–79 years group, high-grade serous (68.3%) represented the leading histological type. Most young women were diagnosed at stage I (57.7%), while most old women were diagnosed at stage (48.1%). Both 5-year OS and 5-year CSS were higher in < 35 years group (5-year OS: 76.00% vs 40.18%, p < 0.001; 5-year CSS: 83.56% vs 55.18%, p < 0.001). The multivariate analysis identified histological type and stage as prognostic factors for CSS in both groups. Endometrioid represented a positive predictor for CSS, while carcinosarcoma and malignant Brenner were related to a worse CSS. (< 35 years group: carcinosarcoma vs endometrioid: HR 5.630, p=0.024; malignant Brenner vs endometrioid: HR 4.005, p < 0.001; 60–79 years group: carcinosarcoma vs endometrioid: HR 3.606, p < 0.001; malignant Brenner vs endometrioid: HR 2.291, p < 0.001). Tumors laterality, CA125 levels, surgery and lymphadenectomy failed to be associated with the CSS in < 35 years group, while found to be independent risk factors in 60–79 years group.ConclusionEOC women aged under 35 had a better survival outcome over EOC women aged 60–79, owing to high proportion of endometrioid and mucinous types in histology, as well as early-stage diagnosis. Identification of histological types and gene profiles should be underscored in young EOC patients.

The hybrid CMC and superalloy bolted joints have exhibited great potential to be used as thermostructural components of reusable space transportation systems, given the respective strengths of these two materials. In the high temperature excursion of the hybrid joints with the aircrafts and space vehicles, the substantial difference in thermal expansion coefficients of CMC and superalloy materials will induce complex superposition of initial assembly stress, thermal stress, and tensile stress around fastening area, which might lead to unknown failure behavior of joint structure. To address this concern, a finite element model embedded with progressive damage analysis was established to simulate the thermostructural behavior and high-temperature tensile performance of single-lap, single-bolt C/SiC composite and superalloy joint, by using the ABAQUS software. It was found that the initial stiffness of the CMC/superalloy hybrid bolted joints decreases with the rise of applied temperature under all bolt-hole clearance levels. However, the load-bearing capacity varies significantly with the initial clearance level and exposed temperature for the studied joint. The thermal expansion mismatch generated between the CMC and superalloy materials led to significant changes in the assembly preload and bolt-hole clearance as the high-temperature load is applied to the joint. The evolution in the thermostructural behavior upon temperature was then correlated with the variations in stiffness and failure load of the joints. The provided new findings are valuable for structural design and practical application of the hybrid CMC/superalloy bolted joints at high temperatures in next-generation aircrafts.

Abstract Background Angiostrongylus cantonensis, an important foodborne parasite, can induce serious eosinophilic meningitis in non-permissive hosts, such as mouse and human. However, the characteristics and mechanisms of the infection are still poorly understood. This study sought to determine the key molecules and its underlying mechanism in inducing brain eosinophilic infiltration caused by Angiostrongylus cantonensis. Methods Mathematical models were established for prediction of significantly changing genes and the functional associated protein with RNA-seq data in Angiostrongylus cantonensis infection. The expression level of Chi3l3, the predicted key molecule, was verified using Western blotting and real-time quantitative PCR. Critical cell source of Chi3l3 and its relationship with eosinophils were identified with flow cytometry, immunohistochemistry, and further verified by macrophage depletion using liposomal clodronate. The role of soluble antigens of Angiostrongylus cantonensis in eosinophilic response was identified with mice airway allergy model by intranasal administration of Alternaria alternate. The relationship between Chi3l3 and IL-13 was identified with flow cytometry, Western blotting, and Seahorse Bioscience extracellular flux analyzer. Results We analyzed the skewed cytokine pattern in brains of Angiostrongylus cantonensis-infected mice and found Chi3l3 to be an important molecule, which increased sharply during the infection. The percentage of inflammatory macrophages, the main source of Chi3l3, also increased, in line with eosinophils percentage in the brain. Network analysis and mathematical modeling predirect a functional association between Chi3l3 and IL-13. Further experiments verified that the soluble antigen of Angiostrongylus cantonensis induce brain eosinophilic meningitis via aggravating a positive feedback loop between IL-13 and Chi3l3. Conclusions We present evidences in favor of a key role for macrophave-derived Chi3l3 molecule in the infection of Angiostrongylus cantonensis, which aggravates eosinophilic meningitis induced by Angiostrongylus cantonensis via a IL-13-mediated positive feedback loop. These reported results constitute a starting point for future research of angiostrongyliasis pathogenesis and imply that targeting chitinases and chitinase-like-proteins may be clinically beneficial in Angiostrongylus cantonensis-induced eosinophilic meningitis.

Balanced homodyne detector (BHD) that can measure the field quadratures of coherent states has been widely used in a range of quantum information technologies. Generally, the BHD tends to suffer from narrow bands and an expanding bandwidth behavior usually traps into a compromise with the gain, electronic noise, and quantum to classical noise ratio, etc. In this paper, we design and construct a wideband BHD based on radio frequency and integrated circuit technology. Our BHD shows bandwidth behavior up to 1.2 GHz and its quantum to classical noise ratio is around 18 dB. Simultaneously, the BHD has a linear performance with a gain of 4.86 k and its common mode rejection ratio has also been tested as 57.9 dB. With this BHD, the secret key rate of continuous-variable quantum key distribution system has a potential to achieve 66.55 Mb/s and 2.87 Mb/s, respectively, at the transmission distance of 10 and 45 km. Besides, with this BHD, the generation rate of quantum random number generator could reach up to 6.53 Gb/s.

Heavy metal contamination in groundwater is a serious environmental problem. Many microorganisms that survive in subsurface porous media also produce extracellular polymeric substances (EPS), but little is known about the effect of these EPS on the fate and transport of heavy metals in aquifers. In this study, EPS extracted from soil with a steam method were used to study the adsorption behaviors of Cu2+ and Cd2+, employing quartz sand as a subsurface porous medium. The results showed that EPS had a good adsorption capacity for Cu2+ (13.5 mg/g) and Cd2+ (14.1 mg/g) that can be viewed using the Temkin and Freundlich models, respectively. At a pH value of 6.5 ± 0.1 and a temperature of 20 °C, EPS showed a greater affinity for Cu2+ than for Cd2+. The binding force between EPS and quartz sand was weak. The prior saturation of the sand media with EPS solution can significantly promote the migration of the Cu2+ and Cd2+ in sand columns by 8.8% and 32.1%, respectively. When treating both metals simultaneously, the migration of Cd2+ was found to be greater than that of Cu2+. This also demonstrated that EPS can promote the co-migration of Cu2+ and Cd2+ in saturated porous media.

We propose a method to improve the performance of two entanglement-based continuous-variable quantum key distribution protocols using noiseless linear amplifiers. The two entanglement-based schemes consist of an entanglement distribution protocol with an untrusted source and an entanglement swapping protocol with an untrusted relay. Simulation results show that the noiseless linear amplifiers can improve the performance of these two protocols, in terms of maximal transmission distances, when we consider small amounts of entanglement, as typical in realistic setups.