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Objective. To explore the effects of improved oral care on the number of oropharyngeal bacteria and the incidence of ventilator-associated pneumonia in patients undergoing mechanical ventilation through oral endotracheal intubation by improving conventional oral care methods and operating procedures and to evaluate the quality of improved oral care and effect. Methods. A total of 100 cases of mechanically ventilated patients with oral endotracheal intubation who met the inclusion criteria were randomly divided into the observation group and control group with 50 cases each. The control group took routine oral care, that is, scrubbing 3 times per day, and the oral care solution was selected as physiological brine. The observation group improved the conventional oral care method, namely, oral scrubbing before intubation, brushing and washing after intubation, 3 times per day, and 0.1% povidone-iodine in oral care solution. Analysis and comparison of the oral bacterial flora, oral cleanliness, and incidence of ventilator-associated pneumonia, mechanical ventilation time, ICU hospitalization time, and mortality rate of the two groups of patients were analyzed and compared. The relevant data were collected and processed for statistical processing. Results. The oral bacterial flora of the two groups of patients before oral care after mechanical ventilation after oral tracheal intubation was compared, and there was no significant statistical difference ( P > 0.05 ). After nursing, the oral bacterial flora of the observation group at 8 h, 16 h, and 24 h after intubation was significantly lower than that of the control group. Statistics showed that the difference was statistically significant ( P < 0.05 ). After nursing, the number of patients with oral cleanliness in the observation group was significantly higher than that of the control group, while the incidence of ventilator-associated pneumonia in the observation group was 8% significantly lower than that of the control group 14%. Statistics show that this difference is statistically significant ( P < 0.05 ). After nursing, the observation group’s oral cleanliness score, mechanical ventilation time, ICU hospitalization time, and GCS score were better than those of the control group. Statistics showed that the difference was statistically significant ( P < 0.05 ). The mortality of the observation group was significantly lower than that of the control group, which was not statistically significant ( P > 0.05 ). Conclusion. Oral care can effectively reduce the number of oropharyngeal bacteria in patients who are mechanically ventilated through orotracheal intubation and significantly reduce the incidence of ventilator-associated pneumonia.

Background Shoulder pain is commonly reported after hepatic surgery; however, the factors affecting post-hepatectomy shoulder pain remain unclear. This study aimed to determine the incidence and risk factors of shoulder pain after hepatectomy. Methods This prospective cohort study recruited 218 patients who underwent hepatic resection at our hospital from June to September 2022. Data were obtained from electronic medical records and follow-up assessments on the second postoperative day. All patients denied chronic pain before surgery. In this cohort study, patients were grouped according to the appearance of shoulder pain. Demographic information and perioperative data were compared between the two groups. The relationship between shoulder pain and independent variables was assessed using univariate binary logistic regression analysis. The potential risk factors were analyzed using multivariable binary logistic regression. Results Of the 218 patients enrolled in this cohort study, 91 (41.7%) reported shoulder pain. Patients in the case group were significantly younger than those in the control group (P = 0.001). Epidural anesthesia was used more frequently in the case group (P = 0.012). Patients over 60 years of age showed a lower incidence of shoulder pain than younger patients (P = 0.028). According to multivariable binary logistic regression analysis, advanced age and epidural anesthesia were associated with risk of shoulder pain (advanced age: odds ratio [OR] [95% confidence interval (CI)]: 0.96 [0.94, 0.99], P = 0.002; epidural anesthesia: OR [95% CI]: 2.08 [1.18, 3.69], P = 0.012). Conclusions The incidence of acute shoulder pain after hepatectomy is 41.7%. The application of epidural anesthesia is an independent risk factor for shoulder pain after hepatectomy, whereas advanced age is a protective factor.

Background Endostatin and bevacizumab have been approved for the first-line treatment of advanced non-small-cell lung cancer (NSCLC) patients in China; however, the clinical outcomes for each drug combined with platinum-based doublet chemotherapy (PT-DC) have not yet been directly compared. This study sought to assess the clinical outcomes of the 2 drugs combined with PT-DC in the first-line treatment of patients with advanced lung adenocarcinoma. Methods This retrospective cohort study examined the clinical data of patients with metastatic or recurrent lung adenocarcinoma (LUAD) treated with endostatin or bevacizumab combined with PT-DC as the first-line treatment from October 2010 to November 2019. Propensity score matching (PSM) was performed using a 1:1 ratio nearest neighbor algorithm. The effectiveness and safety outcomes for the 2 groups were evaluated. Results A total of 202 patients were enrolled in the study. Of these, the endostatin group comprised 124 patients and the bevacizumab group comprised 78 patients; 67 pairs of patients were identified after PSM. The progression-free survival (PFS) and overall survival (OS) of patients treated with PT-DC + endostatin and PT-DC + bevacizumab were compared [(PFS: before PSM 4.8 vs. 6.5 months, P=0.741; after PSM 6.5 vs. 6.1 months, P=0.402), (OS: before PSM 21.1 vs. 39.3 months, P=0.912; after PSM 23.6 vs. 39.3 months, P=0.579)]. The objective response rates (ORRs) and disease control rates (DCRs) of the 2 groups were comparable (37.7% vs. 50.7%, P=0.094; 89.6% vs. 92.5%, P=0.545). Adverse events (AEs) ≥ grade 3 were not observed in the PT-DC + endostatin group. Three (3.8%) cases of AEs ≥ grade 3 were observed the PT-DC + bevacizumab group, comprising hypertension (n=1), proteinuria (n=1), hemoptysis (n=1). Conclusions This retrospective analysis showed that in first-line treatments, PT-DC + endostatin and PT-DC + bevacizumab appear to produce similar anti-tumor activities in patients with metastatic or recurrent lung adenocarcinoma. PT-DC + bevacizumab tended to result in worse adverse reactions than PT-DC + endostatin.

Background The combination of PD-1/PD-L1 inhibitor and chemotherapy has been clinically confirmed to be beneficial as the first-line treatment of patients with advanced NSCLC. This study aimed to assess the effect of nivolumab + docetaxel versus nivolumab monotherapy in patients with NSCLC after the failure of platinum doublet chemotherapy. Materials and methods The efficacy and toxicity of nivolumab + docetaxel combination therapy versus nivolumab monotherapy were compared in this retrospective study. Primary endpoint of the study was progression-free survival (PFS), and the secondary endpoints were objective response rate (ORR), overall survival (OS), and toxicity. Results Between November 2017 and December 2019, 77 patients were included in this study, with 58 patients in the nivolumab group and 19 in the nivolumab + docetaxel group. The median follow-up was 18 months, and the PFS was 8 months for patients receiving nivolumab + docetaxel and 2 months for those receiving nivolumab alone (p = 0.001), respectively. Nivolumab + docetaxel showed superior OS compared with nivolumab, with the median OS unreached versus 7 months (p = 0.011). Among patients without EGFR/ALK variation, compared to nivolumab monotherapy, nivolumab + docetaxel showed better PFS (p = 0.04) and OS (p = 0.05). There was no significant difference in grade 3–4 adverse events (AEs) between the two groups (p = 0.253). Conclusions The combination of nivolumab and docetaxel demonstrated a meaningful improvement in progression-free survival and overall survival compared to nivolumab monotherapy, in patients with NSCLC after the failure of platinum doublet chemotherapy, irrespective of EGFR/ALK variation status.

Purpose. To evaluate the diagnostic value of carcinoembryonic antigen (CEA) combined with inflammatory cell ratios in colorectal cancer (CRC). Methods. This retrospective study compared the data of CRC patients with healthy controls. The CEA levels were measured, and the neutrophil-to-lymphocyte ratio (NLR), derived neutrophil-to-lymphocyte ratio (d-NLR), platelet-to-lymphocyte ratio (PLR), and monocyte-to-lymphocyte ratio (MLR) were calculated. The receiver-operating characteristic (ROC) curve was used to assess the diagnostic value of each marker and combined detection. Spearman’s rank correlation test was used to analyze the correlation between CEA and NLR, d-NLR, and PLR. Results. Inflammatory cell ratios and CEA were significantly higher in the CRC group. ROC curve analysis showed that NLR, d-NLR, and PLR had good diagnostic efficacy. The threshold showed that NLR, d-NLR, and PLR were all related to TNM stage, not to age, gender, tumor location, and degree of differentiation. CEA combined with NLR, d-NLR, and PLR (CNDNP) had a significant diagnostic value in CRC. Correlation studies showed that CEA was positively correlated with NLR and d-NLR but not with PLR. Conclusion. The combination of CEA with CNDNP might be a valuable indicator for CRC diagnosis.

On the basis of real-world clinical data, the study aimed to explore the effect and mechanisms of the treatment plan of “traditional Chinese medicine (TCM) regulating liver regeneration.” A total of 457 patients with HBV-related liver failure were retrospectively collected. The patients were divided into three groups: the modern medicine control group (MMC group), patients treated with routine medical treatment; the control group combining traditional Chinese and Western medicine (CTW), patients treated with routine medical treatment plus the common TCM formula; and the treatment group of “TCM regulating liver regeneration” (RLR), patients treated with both routine medical treatment and the special TCM formula of RLR. After 8 weeks of treatment, the mortality of patients in the RLR group (12.31%) was significantly lower than those in the MMC (50%) and CTW (29.11%) groups. Total bilirubin level significantly decreased and albumin increased in the RLR group when compared with the MMC and CTW groups (P < 0.05). In addition, there were significant differences in the expression of several cytokines related to liver regeneration in the RLR group compared with the MMC group. RLR treatment can decrease jaundice, improve liver function, and significantly reduce the mortality in patients with HBV-related liver failure. The mechanism may be related to the role of RLR treatment in influencing cytokines related to liver regeneration.

OBJECTIVES This study aimed to evaluate changes in validated symptom scores at intake and discharge in women undergoing pelvic floor physical therapy (PFPT) for pain and other pelvic floor symptoms. METHODS Consecutive women starting PFPT during 1 year were reviewed. History, demographics, and Pelvic Floor Distress Inventory Questionnaire - Short Form 20 (PFDI) total and domain scores (Pelvic Organ Prolapse Distress Inventory-6, Urogenital Distress Inventory-6, Colorectal-Anal Distress Inventory-8), Pelvic Floor Impact Questionnaire (PFIQ-7), and pain levels on a numeric rating scale (NRS) were collected at intake and discharge. Data were analyzed with descriptive statistics and sign tests. RESULTS Of 474 women, mean age was 50.3 ± 16.7 years (range, 18-87 years) and the most common indication for PFPT was pelvic pain (208/474; 43.9%). In women with complete data, pretreatment to posttreatment median scores improved on the PFDI (77.3 vs 41.8; P < 0.0001), Urogenital Distress Inventory (37.5 vs 16.0; P < 0.0001), and PFIQ (58.0 vs 19.0; P < 0.0001), and the minimal clinically important difference was met for the PFDI, PFIQ, and Colorectal-Anal Distress Inventory. Women with primarily pelvic pain (n = 208) achieved significant improvements in PFDI, PFIQ, and NRS scores (P < 0.0001 for all) as well as the minimal clinically important difference for these measures. Pain patients with a history of pelvic surgery (n = 50) also had significant improvements in PFIQ and NRS but not PFDI scores. CONCLUSIONS Most women referred to PFPT demonstrated symptom improvements as measured by validated instruments.

The purpose of this prospective phase II clinical trial was to investigate the efficacy and safety of anlotinib in patients with relapsed small cell lung cancer (SCLC). Forty‐five patients with relapsed SCLC were enrolled and treated with anlotinib (one cycle of 12 mg daily for 14 days, discontinued for 7 days, and repeated every 21 days) until disease progression or intolerance of treatment. The primary end point was progression‐free survival (PFS). Secondary end points were overall survival (OS), disease control rate (DCR), objective control rate (ORR) and toxicity. The median PFS was 4.1 months (95% confidence interval [CI] 2.4‐5.8) and the median OS was 6.1 months (95% CI 2.2‐10.0). The OS for the limited‐stage subgroup was significantly longer than that of the extensive‐stage subgroup (P = .02). The DCR was 67%, and the ORR was 11%. The most common adverse event was hypertension (13%), which was controlled well with antihypertensive drugs. In conclusion, anlotinib has likely efficacy in patients with relapsed SCLC, and the side effects can be well tolerated. A longer OS was observed in limited‐stage SCLC patients treated with anlotinib., What's new? Although untreated small cell lung cancer (SCLC) patients are usually sensitive to chemotherapy, they are prone to relapse. Anlotinib is a novel multi‐target small molecule tyrosine kinase inhibitor with both anti‐angiogenesis and anti‐tumor growth effects. While anlotinib became the first drug approved for third‐line and further‐line treatment of SCLC in China, few studies have focused on anlotinib treatment in relapsed SCLC. This one‐arm, prospective phase II clinical study reports a median progression‐free survival of 4.1 months (95% CI 2.4‐5.8) and median overall survival of 6.1 months (95% CI 2.2‐10.0) for anlotinib treatment in relapsed SCLC, with relatively mild side effects.

Purposes: To describe the development and validation of an artificial intelligence-based, deep learning algorithm (DeepDR) for the detection of diabetic retinopathy (DR) in retinal fundus photographs. Methods: Five hundred fundus images, which had detailed labelling of DR lesions, were transmitted to be analysed, including localization of the optic disk and macular, vessel segmentation, detection of lesions, and grading of DR. The multi-level iterative method of convolutional neural network and the strategy of enhanced learning were used to improve the accuracy of the system (DeepDR) for grading DR. Three public data sets were used to further train the software. The final grading results were tested based on the fundus images provided by the hospitals. Results: For 6788 fundus images (both macular and disc centred) of two Hospital Eye Center, the detection of microaneurysm, haemorrhage and hard exudates had an accuracy of 99.7%, 98.4% and 98.1%, respectively. The current algorithm accuracy was 0.96. Another 20,000 fundus images from community screening were selected, and 7593 photos of poor quality were excluded according to quality standards. Accuracy for accurate staging of fundus photos: accuracy was 0.9179. The sensitivity, specificity and area under the curve (AUC) were 80.58%, 95.77% and 0.9327, respectively. Conclusions: This artificial intelligence-based DeepDR can be used with high accuracy for the detection of DR in retinal images. This technology offers the potential to increase the efficiency and accessibility of DR screening programs.

Efficient signal amplification is essential to construct ultrasensitive biosensors for biologically relevant species with abundant concomitant interferences. Here, we apply LbaCas12a as a signal amplifier to develop a versatile CRISPR-Cas12a platform to detect a wide range of analytes in ultralow concentrations. The platform relies on the indiscriminate single-stranded DNase activity of LbaCas12a, which recognizes single-stranded DNA intermediates generated by non-DNA targets down to femtomolar concentrations and subsequently enhances the fluorescence signal output. With the help of functional nucleotides (DNAzyme and aptamer), ultrasensitive bioassays for Pb2+ and Acinetobacter baumannii have been designed with a limit of detection down to ∼0.053 nM and ∼3 CFU/mL, respectively. It also allows simultaneous detection of four microRNAs (miRNAs) at a picomolar concentration without significant interferences by other counterparts, suggesting the potential of multiplexed miRNA expression profiles analysis in high throughput. Given the versatility and generality of the CRISPR-Cas12a platform, we expect the current work to advance the application of CRISPR-Cas-based platforms in bioanalysis and provide new insights into ultrasensitive biosensor design.

Objective: Pembrolizumab and bevacizumab both have antitumor activity. According to NCCN updated guideline the benefit of pembrolizumab or bevacizumab as a first line in management of advanced nonsmall cell lung cancer (NSCLC) is documented in randomized controlled studies. The study aimed to evaluate the response and complications of patients with advanced NSCLC treated with pembrolizumab or bevacizumab plus chemotherapy. Methods: This study was a retrospective cohort study of patients with advanced nonsquamous NSCLC who received cisplatin with pemetrexed combined with pembrolizumab (A group) or bevacizumab (B group) from 07/02/2018 to 07/03/2021 at Peking University Cancer Hospital. Progression-free survival (PFS) was the primary outcome. The secondary outcomes included overall survival (OS), objective response rate (ORR), disease control rate (DCR), duration of response (DoR), and adverse events (AEs). Results: This study included 66 patients, 34 in A group and 32 in B group. There were no differences in median PFS (7.6 vs 9.9 months, P = .601). There were no differences in median OS (23.1 vs 24.2 months, P = .782). There were no differences in ORR (57.6 % vs 41.9 %, P = .211) and DCR (93.9 % vs 100.0 %, P = .164) between 2 groups. The occurrence of AEs was similar. No new safety signals were observed. Grade 3 to 4 treatment-related AEs occurred in 17 (50.0 %) patients of A group and in 12 (37.5 %) of B group ( P > .05). Conclusion: The addition of pembrolizumab or bevacizumab to pemetrexed plus cisplatin was well tolerated and resulted in a clinically meaningful treatment benefit in advanced nonsquamous NSCLC. When pembrolizumab is not suitable, bevacizumab plus chemotherapy may be an option.

This study aimed to analyze the application of ultrasound images of lung recruitment (LR) nursing treatment guided by positive-end expiratory pressure (PEEP) in patients with acute respiratory distress syndrome (ARDS). An ultrasound image enhancement algorithm (UIEA) wavelet transform (WT) was constructed, and the soft threshold (ST) and adjacent region average (ARA) were introduced for simulation comparison. In addition, the signal-to-noise ratio (SNR), peak signal-to-noise ratio (PSNR), and running time were undertaken as the evaluation indexes. The WT algorithm was applied to the ultrasound images of 85 ARDS patients before and after PEEP recruitment. The mean artery pressure (MAP), heart rate (HR), and central venous pressure (CVP), peak inspiratory pressure (Ppeak), mean inspiratory pressure (Pmean), dynamic lung compliance (DLC), PCO2, and PaO2/FiO2 of the patients were recorded before and after the LR. The results showed that the signal-to-noise ratio (SNR) (19.67 ± 3.15 dB) and PSNR (23.08 ± 2.08 dB) of the images enhanced by the WT algorithm were much higher than those of ST (13.88 ± 2.74 dB and 14.62 ± 1.76 dB, respectively) and ARA (14.96 ± 3.06 dB and 15.11 ± 1.94 dB, respectively), while the running time was in adverse ( P < 0.05 ); the HR and CVP of patients after LR nursing treatment were increased greatly, while the MAP was in the opposite case ( P < 0.05 ); after LR nursing treatment, Ppeak, Pmean, DLC, PCO2, and PaO2/FiO2 of the patient were significantly greater than those before the LR, and the difference was statistically significant ( P < 0.05 ). In short, the WT algorithm not only enhanced the quality of ultrasound images but also shortened the running time and improved the processing efficiency. PEEP LR nursing treatment could effectively improve the vascular patency, cardiac ejection capacity, and DLC in patients with ARDS, thereby increasing the airway pressure and maintaining the unobstructed expiration.

To systematically search and sort out the clinical randomized controlled trial(RCT) on the prevention and treatment of acute cerebral infarction with traditional Chinese medicine(TCM) by using the method of evidence map, and to understand the evidence distribution of related studies. CNKI, Wanfang, VIP, CBM, PubMed, EMbase, Cochrane Library and Web of Science were retrieved from January 2016 to September 2020, and literatures related to the prevention and treatment of acute cerebral infarction with traditional Chinese medicine were included. Text description combined with table and bubble chart were used to analyze the distribution characteristics of evidence. A total of 1 102 clinical articles in recent five years were retrieved. The annual trend of clinical study publication, study size, TCM therapy category and main scheme, and study literature quality were analyzed. We find that TCM treatment of acute cerebral infarction has become a hot topic of clinical research, the number of literature showed a trend of increased year by year, various means of intervention of TCM in the treatment of the advantages of increasingly highlight. Follow-up clinical research should highlight the characteristics of TCM: in the analysis of outcome indicators; increase the neuropsychological patients after stroke and cognitive ability, and the theory of combined treatment of TCM disease when thoughts; At the same time, the quality of clinical research needs to be improved. At present, there is still a lack of unified standards for the production of evidence map. This study is the first to explore the application of evidence map to summarize and display the clinical research status of TCM treatment of acute cerebral infarction, and combine it with the setting of priority areas of TCM clinical research, so as to provide a reference basis for determining the priority topic selection of TCM treatment optimization research.

To overview the systematic reviews of Panax notoginseng saponins in the treatment of acute cerebral infarction. CNKI, CBM, Wanfang, VIP, PubMed, Cochrane Library and EMbase databases were retrieved to collect the systematic reviews of the efficacy of P. notoginseng saponins in the treatment of acute cerebral infarction. The retrieval time was from the time of database establishment to January 2021. After two researchers independently screened out the literature and extracted the data, AMSTAR-2 scale was used to evaluate the methodological quality of the included systematic reviews, GRADE system was used to grade the quality of evidences of the outcome indicators, and the efficacy evaluation was summarized. A total of 5 systematic reviews were included. AMSTAR-2 evaluation results showed that 3 items were relatively complete, while 4 items had a poor overall quality. P. notoginseng saponins combined with conventional Western medicine therapy was superior to single conventional therapy in the recovery of neurological function, enhancement of the total effective rate in clinic, and improvement of activities of daily living. GRADE evaluation results showed that the quality of evidence was from low quality to very low quality. In conclusion, in the treatment of acute cerebral infarction, P. notoginseng saponins can improve the clinical efficacy, with a good safety but a not high methodological quality and a low evidence quality. It is suggested that high-quality clinical studies shall be further carried out to provide evidence-based basis for the application of P. notoginseng saponins in the treatment of acute cerebral infarction.

There have been many clinical trials, systematic reviews/Meta-analysis proving that Xingnaojing Injection has a good clinical efficacy in treatment of cerebral ischaemic stroke, but with fewer comprehensive descriptions. In this study, an overview of systematic reviews/Meta-analysis of Xingnaojing Injection in treating cerebral ischaemic stroke was performed to provide current situation of evidences and basis for clinical practice. CNKI, Wanfang, VIP, CBM, EMbase, PubMed, Cochrane Library, Web of Science were retrieved through computers. A total of 6 literatures were included in this study. By AMSTAR-2 checklist and GRADE, the quality of included systematic reviews and the efficacy of Xingnaojing Injection were evaluated. The results of AMSTAR-2 checklist showed an extremely low quality for all of the 6 systematic reviews. According to the results of GRADE evaluation, among 55 outcomes, there were 2 outcomes with a medium quality, 4 outcomes with a low quality and 49 outcomes with an extremely low quality. The 6 systematic reviews reached a consistent conclusion that Xingnaojing Injection was effective in the treatment of cerebral ischaemic stroke. This therapy could improve the total efficacy, neurological deficit scores, hemodynamic and hemodynamic parameters. However, the methodolo-gical quality of all literatures was extremely low. The evidence levels of outcomes were between extremely low to medium. The effectiveness of Xingnaojing Injection in the treatment of cerebral ischaemic stroke still needs to be further verified by more high-quality studies. In the future, relevant clinical studies and systematic reviews/Meta-analysis shall be carried out in a strict accordance with relevant regulations.

To analyze the use of outcome indicators of randomized controlled trial(RCT) of acupuncture in the treatment of acute ischemic stroke in recent three years, so as to provide a basis for building a study on the core outcome indicators for the treatment of acute ischemic stroke with acupuncture. The RCTs of acupuncture treatment for acute ischemic stroke in recent three years were collec-ted through computer retrieval of eight Chinese and English databases and two clinical trial registries at home and abroad. Literature was screened out, and data was extracted. Risk of assessment bias tool Cochrane 6.1 was used for bias risk assessment, outcome indicators were summarized and analyzed. A total of 47 RCTs were included, and 3 studies were trials registration scheme. Outcome indicators were divided into 6 categories according to functional attributes, namely physical symptoms/signs, physical and chemical examination, quality of life, traditional Chinese medicine symptoms/syndromes, safety events and long-term prognosis. The study found that in addition to the common problems in previous studies covered by the status quo of outcome indicators selection of RCT of acupuncture in the treatment of acute ischemic stroke, there were also the other problems as follows: emphasis on macroscopic efficacy indicators but neglect of acupuncture specific indicators, lack of characteristic indicators and economic indicators of traditional Chinese medicine therapy, and unification of indicators measurement tool and measurement time point. In the future, the outcome indicators set for the treatment of acute ischemic stroke with acupuncture shall be established, and the core outcome indicators set shall be in line with the characteristics of traditional Chinese medicine treatment.

BackgroundNumerous variants of uncertain significance (VUSs) have been identified by whole exome sequencing in clinical practice. However, VUSs are not currently considered medically actionable.ObjectiveTo assess the splicing patterns of 49 VUSs in 48 families identified clinically to improve genetic counselling and family planning.MethodsForty-nine participants with 49 VUSs were recruited from the Reproductive and Genetic Hospital of CITIC-Xiangya. Bioinformatic analysis was performed to preliminarily predict the splicing effects of these VUSs. RT-PCR and minigene analysis were used to assess the splicing patterns of the VUSs. According to the results obtained, couples opted for different methods of reproductive interventions to conceive a child, including prenatal diagnosis and preimplantation genetic testing (PGT).ResultsEleven variants were found to alter pre-mRNA splicing and one variant caused nonsense-mediated mRNA decay, which resulted in the reclassification of these VUSs as likely pathogenic. One couple chose to undergo in vitro fertilisation with PGT treatment; a healthy embryo was transferred and the pregnancy is ongoing. Three couples opted for natural pregnancy with prenatal diagnosis. One couple terminated the pregnancy because the fetus was affected by short-rib thoracic dysplasia and harboured the related variant. The infants of the other two couples were born and were healthy at their last recorded follow-up.ConclusionRNA splicing analysis is an important method to assess the impact of sequence variants on splicing in clinical practice and can contribute to the reclassification of a significant proportion of VUSs. RNA splicing analysis should be considered for genetic disease diagnostics.

Purpose: As midwives witness and attend the whole process of childbirth, they have a better understanding of which factors may cause traumatic childbirth. However, because most of the studies paid their attention on mothers, little is known about psychological birth trauma from the perspective of midwives. This study aims to gain a full understanding of which factors may contribute to psychological traumatic childbirth from the perspective of midwives. Methods: A qualitative research was conducted using in-depth interviews, which involved fourteen midwives from the maternal ward of a tertiary hospital. The interviews were recorded and transcribed, and then, Colaizzi's method was used to analyze the contents of the interviews. Results: We proposed four themes and eight subthemes on the influencing factors of psychological traumatic childbirth from the perspective of midwives: low perceived social support (lack of support from family and lack of support from medical staff), hard times (protracted labor in the first stage and futile efforts during the second stage), poor birth outcomes (poor birth outcomes of the mother and poor birth outcomes of the baby), and excruciating pain (unbearable pain of uterine contraction and labor pain was incongruent with the mother's expectations). Conclusion: Medical staff should pay attention to psychological traumatic childbirth and its effects, and emphasis on the screening and assessment of birthing women with negative feelings so that their psychological traumatic childbirth can be prevented and decreased. Keywords: labor pain, midwifery, natural childbirth, psychological trauma, social support

Background Salivary adenoid cystic carcinoma (SACC) can recur after removal of the primary tumor and treatment, where they can keep no clinical symptoms and dormant state for 10–15 years. NR2F1 has been demonstrated to regulate the tumor cell dormancy in various malignant tumors and has a potential impact on recurrence and metastasis of carcinoma. However, the role and significance of NR2F1 in SACC dormancy still remain unknown. Methods A total number of 59 patients with a diagnosis of SACC were included to detected expression of NR2F1, Ki-67 by immunohistochemical (IHC) staining and terminal deoxynucleotidyl transferase-mediated dUTP nick and labeling (TUNEL). Fisher’s exact test was used to examine the NR2F1 expression and clinicopathologic parameters of SACC. In vitro, SACC cell lines were transfected NR2F1 and knockdown NR2F1 respectively. CCK-8, flow cytometry, wound healing assay and transwell invasion determined SACC cell proliferation, apoptosis, cell cycle, migration and invasion respectively. Chromatin immunoprecipitation (ChIP) assays were utilized to demonstrate the potential role of NR2F1 in SACC invasion via CXCL12/CXCR4 axis. In vivo, xenografts of nude mice via subcutaneous injection or tail vein injection were used to testify the results in vitro. Results Among the 59 patients with SACC, 23.73% (14/59) were positive to NR2F1 expression, a lower rate of expression compared with 60% (6/10) in normal salivary gland samples. NR2F1 was correlated with metastasis, relapse and dormancy of SACC. SACC cells with transfected NR2F1 remained dormant, as well as enhanced invasion and metastasis. Knockdown of NR2F1 via siRNA after NR2F1 overexpression restored the proliferation and the cell number in G2/M phases, and reduced the abilities of migration and invasion. In addition, NR2F1 promoted the expression of CXCL12 and CXCR4, and overexpression of CXCL12 at least partly rescued the proliferation, migration, and invasion activities induced by NR2F1 silencing. Conclusions NR2F1 may be an underlying mechanism of SACC recurrence and metastasis via regulating tumor cell dormancy through CXCL12/CXCR4 pathway.

Background This real‐world study assessed the efficacy and toxicity of anlotinib as salvage treatment in Chinese patients with advanced non‐small cell lung cancer (NSCLC). Methods The medical records of 81 patients with advanced NSCLC who had failed at least two lines of chemotherapy were retrospectively collected. All patients were administered anlotinib treatment until disease progression or intolerance as a result of adverse events. Survival curves were created using the Kaplan–Meier method. The log‐rank test was used for univariate analysis of progression‐free survival (PFS) between groups. Cox regression was used to estimate the statistically significant factors based on univariate analysis. Results The median PFS was five months (95% confidence interval [CI] 3.5–6.5). The objective response rate (ORR) was 7% and the disease control rate (DCR) was 84%. The following subgroups of patients had longer PFS (P

Climate change caused by carbon emissions has a strong influence on the economy and human society. Though numerous previous studies have emphasized the importance of low-carbon innovation on curbing or mitigating carbon emissions, not much attention has been given to the reverse effect. We used a panel of 285 Chinese prefecture-level cities from 2005 to 2016 and Cooperative Patent Classification (CPC)-Y02 patents as low-carbon innovation indicators. The results show that the increasing carbon emissions accelerate cities' low-carbon innovation in China, and the predicted effect varies across low-carbon innovation types. As carbon emissions rise, more low-carbon innovation will occur in activities with higher carbon emissions. Besides, we explore environmental awareness as the mediation channel for carbon emissions to impact low-carbon innovation. With the help of media, government, and enterprises, the growing carbon emissions promote public environmental awareness and change consumers' behaviors, motivating companies to speed up low-carbon innovation.

N 6‐methyladenosine (m6A) modification of mRNA mediates diverse cellular and viral functions. Infection with Epstein–Barr virus (EBV) is causally associated with nasopharyngeal carcinoma (NPC), 10% of gastric carcinoma, and various B‐cell lymphomas, in which the viral latent and lytic phases both play vital roles. Here, we show that EBV transcripts exhibit differential m6A modification in human NPC biopsies, patient‐derived xenograft tissues, and cells at different EBV infection stages. m6A‐modified EBV transcripts are recognized and destabilized by the YTHDF1 protein, which leads to the m6A‐dependent suppression of EBV infection and replication. Mechanistically, YTHDF1 hastens viral RNA decapping and mediates RNA decay by recruiting RNA degradation complexes, including ZAP, DDX17, and DCP2, thereby post‐transcriptionally downregulating the expression of EBV genes. Taken together, our results reveal the critical roles of m6A modifications and their reader YTHDF1 in EBV replication. These findings contribute novel targets for the treatment of EBV‐associated cancers., The m6A reader YTHDF1 promotes viral RNA degradation by recruiting RNA decay complexes, including ZAP, DDX17, and DCP2. YTHDF1 suppresses EBV lytic replication to regulate EBV infection status.

Purpose To identify an optimal cumulative cisplatin dose along with concurrent chemoradiotherapy (CC-CCD) for children and adolescents with locoregionally advanced nasopharyngeal carcinoma (CALANPC) using real-world data. Materials and Methods Using an NPC-specific database at our center, 157 patients younger than 19 years old with non-disseminated CALANPC and receiving neoadjuvant chemotherapy (NAC) plus cisplatin-based concurrent chemoradiotherapy (CCRT) were enrolled. Confounding factors were controlled by conducting propensity score matching analysis. Primary endpoints include disease-free survival (DFS) and distant metastasis-free survival (DMFS). Results The optimal threshold for CC-CCD with respect to DFS was 160 mg/m2 based on recursive partitioning analyses (RPA). Therefore, a uniform threshold of 160 mg/m2 (≥160 vs. Conclusion CC-CCD exerts significant treatment effects and 160 mg/m2 CC-CCD may be adequate to provide antitumor effects for CALANPC receiving NAC plus CCRT.

Background The psychological birth trauma is a universal phenomenon in childbearing women. The influences could extend in a wide range, which includes the mothers’ health, mother-infant relationship, partner relationship. The medical staff could even choose to quit playing their part in the birthing process. The phenomenon has gradually garnered attention around the world. However, it has rarely been discussed under Chinese special conditions. The study was to explore Chinese women’s lived experiences of psychological birth trauma during labor and birth. Methods A descriptive phenomenological approach was adopted in this study. Twenty-four women were recruited, who reported having experienced psychological birth trauma. In-depth interviews were conducted within 1 week after birth. Colaizzi’s method was used to analyze the data. Results Twenty-four women participated in the study. Four themes emerged to describe the women’s experience of psychological birth trauma: “How am I supposed to relieve the endless pain?” “ Can’t I be weak?” “Am I not important?” “What uncertainties are waiting for me?” Conclusions The findings provide deep insight into Chinese women’s unique experience of psychological birth trauma. The social and health system could prevent psychological harm during birth and promote maternal health by measures of pain management, thoughtful attention, adequate caring, and prenatal preparation.

The aim of this retrospective study was to analyze the agreement between colposcopic impression and histopathological diagnosis of cervical biopsy. The medical records of patients underwent a colposcopy-guided cervical biopsy at Chengdu Women’s and Children’s Central Hospital between January 2017 and January 2019 were collected, including age, menopausal status, cervical cytology and human papillomavirus (HPV) test results, type of transformation zone, colposcopic diagnosis and histopathological outcomes of cervical biopsy. Colposcopy was carried out using 2011 colposcopic terminology of International Federation for Cervical Pathology and Colposcopy (IFCPC). Related variables were analyzed. A total of 495 patients were collected in this study. The perfect agreement between colposcopic impression and histopathological diagnosis was 46.9%, and the strength of agreement with kappa value was 0.283 (P

As an aggressive subtype of squamous cell carcinoma, basaloid squamous cell carcinoma (BSCC) rarely occurs in the oral and maxillofacial region. The gingiva is an unusual site of BSCC. This study reported a 78-year-old male who presented with left maxillary pain. Clinical examination revealed a gingival mass in the left maxilla. Under microscope, the lesion showed typical comedo necrosis and peripheral palisading. Areas of glandular-like structures were also observed. Immunohistochemistry results revealed that the Ki-67 score of BSCC in this case was 28%, and S-100 was positive in some areas. However, P16 and CK7 were negative. Finally, a diagnosis of BSCC was made based on the pathological and immunohistochemical characteristics. The patient underwent subtotal maxillectomy. After 12 months later, the patient was alive with no evidence of disease. Combined with relevant literature, this article analyzed the clinicopathological features, differential diagnosis, diagnosis, treatment, and prognosis of BSCC. Although surgery remains the main treatment in the head and neck region, radiation-chemotherapy should be considered in some human papilloma virus-positive cases.基底细胞样鳞状细胞癌（BSCC）是一种侵袭性较强的鳞状细胞癌亚型，在口腔颌面部发生较少，牙龈部位尤其少见。本文报告1例78岁男性患者，因左上颌骨疼痛就诊，临床检查发现左上颌骨一牙龈肿块，术后病理见基底细胞样的细胞排列成巢或腺样结构，癌巢内可见粉刺样坏死，周围细胞呈栅栏状排列。免疫组织化学染色结果示Ki-67阳性率28%，S-100阳性，P16及CK7阴性。综合病理特征以及免疫组织化学染色结果，诊断为BSCC。术后随访12个月无复发。结合相关文献，本文对BSCC的临床病理特征、鉴别诊断、诊断、治疗及预后进行分析，认为手术仍是头颈部BSCC的主要治疗方法，但对于人乳头瘤病毒阳性的病例应考虑结合放化疗的综合治疗方式。.

To determine the clinical efficacy and safety of Liangxue Jiedu decoction (LJD) for the treatment of progressive psoriasis vulgaris and to provide the basis for the development of a standardized treatment protocol for psoriasis vulgaris.In this multicenter, randomized, controlled study, patients with blood-heat type psoriasis were randomly assigned to receive either Chinese herbal medicine (LJD; treatment group) or Western Medicine (cetirizine hydrochloride, vitamin C, and vitamin B complex; control group). Psoriasis Area and Severity Index (PASI) scores were calculated in addition to the number of patients who achieved ≥ 50% or ≥ 75% improvement in PASI score from baseline. The change in symptoms of Chinese medicine (color of rash, burning sensation, itchiness, severity of irritation, and anger) was evaluated and safety was assessed as adverse events and laboratory analysis. t test, independent sample non-parametric test and χ2 test were used to analyze the results.A total of 238 participants were included in the study [treatment group, n = 122 (PP analysis 117); control group, n = 116 (PP analysis 104)]. LJD treatment was associated with a significant improvement in skin lesions and symptoms compared with Western Medicine treatment. At the end of the 8-week treatment period, 23.77% (PP analysis 24.79%) of patients in the treatment group had achieved PASI75 and 57.38% (PP analysis 58.97%) had achieved PASI50; the corresponding figures in the control group were 9.48% (9.62%) and 25.00% (25.00%), respectively. The between-group differences were statistically significant (P0.05).Treatment of psoriasis vulgaris of the blood-heat type using LJD was associated with significantly better outcomes compared with those achieved using standard Western Medicine.

Non-small cell lung cancer (NSCLC) with RAS -mutant gene has been the most difficult obstacle to overcome. Over 25% of muted lung adenocarcinomas have RAS mutation. The prognosis of NSCLC patients with RAS-mutant genes is always poor because there is no effective drug to suppress RAS-mutant genes. NSCLC patients with RAS-mutant usually develop resistance to radiotherapy and chemotherapy, which in some cases leads to a 5-10% survival rate for non-small cell lung cancer (NSCLC). As little clinical symptom of NSCLC was presented at its early stages, thus it always brings in disappointing treatment outcome. Currently, NSCLC presents the highest morbidity and mortality all over the world. The combination of PI3K/AKT/mTOR pathway inhibitors with radiotherapy is a novel strategy to improve radiosensitivity and therapeutic outcome of NSCLC with a RAS-mutant gene. There have been many preclinical studies and clinical trials on the effect of PI3K/AKT/mTOR pathway inhibitors combined with radiotherapy in NSCLC with a RAS-mutant gene have been reported in the past years. This review provides current knowledge of the combination of PI3K/Akt/mTOR pathway inhibitors with radiotherapy, which prove to be a significant improvement for the treatment of NSCLC patients with RAS mutations and will benefit NSCLC patients with RAS mutations.

Background Alzheimer's disease (AD) is the most common cause of dementia. Studies indicate that neuroinflammation plays an important role in the pathophysiology of AD. High-mobility group box 1 (HMGB1) is an important chromatin protein. It can be secreted by immune cells and passively released from damaged cells to promote inflammation. HMGB1 also can recruit stem cells and promote their proliferation and tissue repairing. However, the role of HMGB1 in the progression of AD is currently unknown. Objective The aims were to investigate the effect of HMGB1 on the AD-related pathologies and cognitive function using 3×Tg-AD mouse model. Methods Female 5-month-old 3×Tg-AD mice were intracerebroventricularly injected with 4.5 μg of HMGB1 or with saline as a control. The levels of interesting protein were assessed by western blots or immunofluorescence. The effect of HMGB1 on the cognitive function was evaluated by one-trial novel object recognition test and Morris water maze. Results Intracerebroventricular injection of recombinant HMGB1 ameliorated cognitive impairment in 5-6-month-old 3×Tg-AD mice. The levels of synapsin 1, synaptophysin, MAP2, NeuN, and phosphorylated CREB were increased in HMGB1-treated 3×Tg-AD mouse brains. HMGB1 decreased intracellular amyloid-β level but did not affect tau phosphorylation. HMGB1 treatment also promoted neurogenesis in the dentate gyrus and increased the level of GFAP in the 3×Tg-AD mouse brains. Conclusion These results reveal a novel function of HMGB1 in enhancing neuroplasticity and improving cognitive function in 3×Tg-AD mice.

Purpose The tumor-related myeloid derived suppressor cells (MDSCs), important immunosuppressive cells in tumor microenvironment, play an important role in the cancer progression. This study is aimed to investigate the crosstalk between MDSCs and oral squamous cell carcinoma (OSCC) cells and their role in the malignant progression of OSCC. Methods Immunochemistry (IHC) was used to investigate the expression of CD33 in 200 OSCC, 36 premalignant. CD33+ MDSCs were sorted and enriched via magnetic-activated cell sorting (MACS) from OSCC patients or health donor, and their phenotypes were identified by flow cytometry. With a co-culture system of MDSCs and OSCC, the effects of MDSCs on OSCC proliferation, apoptosis, migration invasion, epithelial-mesenchymal transition (EMT), and vasculogenic mimicry formation (VM) formation were assessed, respectively. Besides, peripheral blood mononuclear cells (PBMCs) from health donor were cultured with OSCC supernatant, the level of MDSCs and expressions of Arginase (Arg-1) and inducible nitric oxide synthase (iNOS) were measured. Results The number of MDSCs was increased in tumor tissues of OSCC patients, and was positively related to the T stage, pathological grade, lymph node metastasis and poor prognosis. Tumor-related MDSCs of the co-culture system promoted OSCC progression by contributing to cell proliferation, migration and invasion as well as inducing EMT and VM. In turn, OSCC cells had potential to induce MDSCs differentiation from PBMCs and increase the expression of Arg-1 and iNOS. Conclusion These indicated that the crosstalk between MDSCs and tumor cells facilitated the malignant progression of OSCC cells and the immune suppressive properties of MDSCs, which may provide new insights into tumor treatment on targeting tumor-associated immunosuppressive cells.

Objective: To investigate whether intact umbilical cord milking (I-UCM) can aggravate infection or result in other undesirable complications in preterm infants with premature prolonged rupt...

Retinal screening contributes to early detection of diabetic retinopathy and timely treatment. To facilitate the screening process, we develop a deep learning system, named DeepDR, that can detect early-to-late stages of diabetic retinopathy. DeepDR is trained for real-time image quality assessment, lesion detection and grading using 466,247 fundus images from 121,342 patients with diabetes. Evaluation is performed on a local dataset with 200,136 fundus images from 52,004 patients and three external datasets with a total of 209,322 images. The area under the receiver operating characteristic curves for detecting microaneurysms, cotton-wool spots, hard exudates and hemorrhages are 0.901, 0.941, 0.954 and 0.967, respectively. The grading of diabetic retinopathy as mild, moderate, severe and proliferative achieves area under the curves of 0.943, 0.955, 0.960 and 0.972, respectively. In external validations, the area under the curves for grading range from 0.916 to 0.970, which further supports the system is efficient for diabetic retinopathy grading., As the leading cause of vision loss in working-age adults, diabetic retinopathy requires routinely retinal screening. Here the authors develop a deep learning system that can facilitate the screening by providing real-time image quality assessment, lesions detection, and grades across the disease spectrum.

Ultrasound is the preferred initial imaging modality in Europe and Asia for assessing the major salivary glands. In experienced hands, it is sensitive for a range of salivary pathologies, often diagnostic, and also a safe, cost-effective gatekeeper for further investigations as well as image-guided diagnostic biopsies and aspirations. This article reviews the scanning technique and normal sonographic anatomy of major salivary glands and overviews typical sonographic appearances of salivary pathologies, including infective and inflammatory conditions, sialolithiasis, and neoplasms. Limitations of ultrasound and the current evidence for advanced techniques, including contrast-enhanced ultrasound and ultrasound elastography, are also discussed.

Timely detection and treatment of microaneurysms is a critical step to prevent the development of vision-threatening eye diseases such as diabetic retinopathy. However, detecting microaneurysms in fundus images is a highly challenging task due to the low image contrast, misleading cues of other red lesions, and the large variation of imaging conditions. Existing methods tend to fail in face of the large intra-class variation and small inter-class variations for microaneurysm detection in fundus images. Recently, hybrid text/image mining computer-aided diagnosis systems have emerged to offer a promise of bridging the semantic gap between images and diagnostic information. In this paper, we focus on developing an interleaved deep mining technique to cope intelligently with the unbalanced microaneurysm detection problem. Specifically, we present a clinical report guided multi-sieving convolutional neural network, which leverages a small amount of supervised information in clinical reports to identify the potential microaneurysm regions via the image-to-text mapping in the feature space. These potential microaneurysm regions are then interleaved with fundus image information for multi-sieving deep mining in a highly unbalanced classification problem. Critically, the clinical reports are employed to bridge the semantic gap between low-level image features and high-level diagnostic information. We build an efficient microaneurysm detection framework based on the hybrid text/image interleaving and validate its performance on challenging clinical data sets acquired from diabetic retinopathy patients. Extensive evaluations are carried out in terms of fundus detection and classification. Experimental results show that our framework achieves 99.7% precision and 87.8% recall, comparing favorably with the state-of-the-art algorithms. Integration of expert domain knowledge and image information demonstrates the feasibility of reducing the difficulty of training classifiers under extremely unbalanced data distributions.

Background Accumulating evidence indicates that Tau pathology can spread from neuron to neuron by intake and coaggregation of the hyperphosphorylated Tau (p-Tau) seeds with the host neuron protein. Thus, clearance of Tau seeds by immunization with Tau antibodies could provide a potential therapeutic opportunity to block the spread of the pathology in Alzheimer’s disease (AD) and other tauopathies. We report prevention of the seeding and spread of tau pathology with mouse monoclonal antibody 43D against the N-terminal projection domain of Tau (Tau 6–18) in triple-transgenic AD (3 × Tg-AD) mice. Methods Female 11- to 12-month-old 3 × Tg-AD mice were intravenously immunized weekly for 6 weeks with 15 μg/injection of mouse monoclonal antibody 43D or with mouse immunoglobulin G as a control. AD p-Tau isolated from a frozen autopsied AD brain was unilaterally injected into the right hippocampus on the day of the second dose of immunization. Tau pathology and its effect on Aβ pathology were assessed by immunohistochemical staining. Results We found that the injection of AD p-Tau into the hippocampus of 11- to 12-month-old 3 × Tg-AD mice time-dependently induced Tau aggregation in the hippocampus and promoted the spread of Tau pathology to the contralateral hippocampus. Tau pathology was observed as early as 6 weeks after AD p-Tau injection. Tau pathology templated by AD p-Tau was thioflavin-S-positive and was about two-fold greater than that seen in naive 18-month-old 3 × Tg-AD mice; Tau pathology in the latter was thioflavin-S-negative. Immunization with Tau antibody 43D dramatically blocked AD p-Tau seeding in the ipsilateral hippocampus and inhibited its propagation to the contralateral side in 3 × Tg-AD mice. Furthermore, AD p-Tau injection enhanced the amyloid plaque load in the ipsilateral side, and immunization with 43D showed a tendency to attenuate it. Conclusions These findings indicate that AD p-Tau-injected 3 × Tg-AD mice represent a practical model to study the seeding and spread of Tau pathology, their effect on Aβ pathology, and the effect of Tau immunotherapy on both Tau and Aβ pathologies. Immunization with Tau antibody 43D to Tau 6–18 can prevent the seeding and spread of Tau pathology, making it a potential therapeutic treatment for AD and related tauopathies.

Caprin-1 has been found to promotes osteosarcoma tumor growth, lung metastasis in mice, regulating the proliferation and invasion of human breast cancer cells and up-regulated in proton beam irradiated human melanoma cells. However, its clinical role, biological function in the hepatocellular carcinoma (HCC) remains unknown. In the present study, we investigated the clinical significance of Caprin1 in the HCC. Caprin1 expression was detected by immunohistochemistry, and the expression level was analyzed in 65 HCC tissues and paired peritumoral tissue. Prognostic value of Caprin1 in HCC was evaluated in 174 cases using Kaplan-Meier analysis. Univariate survival analysis and multiple Cox proportional hazards regression were performed using the Cox regression analysis. Immunohistochemistry revealed that Caprin1 expression in 65 HCC tissues was upregulated compared to paired peritumoral tissue (p=0.0064). Survival analysis in 174 HCC patient tissues was showed that high Caprin1 expression was significantly associated with worse overall survival (HR=1.513, p=0.042). In conclusion, high Caprin1 expression independently predicts a poor outcome for patients with HCC, supporting that Caprin1 may be a promising novel HCC prognostic factor.

O-GlcNAcylation is a common posttranslational modification of nucleocytoplasmic proteins with β-N-acetylglucosamine (GlcNAc) and regulates numerous biological processes. By using mouse models of cerebral ischemia induced by permanent and transient middle cerebral artery occlusion (MCAO), we observed an initial elevation (~1.7-fold, 1–4 hours after ischemia) and then decline of O-GlcNAcylation during cerebral ischemia. We found that moderate increase (

Chlorogenic acid (CGA), which is a natural compound found in various plants, has been reported to exert notable anti‑inflammatory activities. The present study investigated the effects and underlying mechanism of CGA on interleukin (IL)‑1β‑induced osteoarthritis (OA) chondrocytes. An in vitro OA‑like chondrocyte model was established using IL‑1β‑stimulated human SW‑1353 chondrocytes. Cell viability was assessed using an MTT assay. Nitric oxide (NO) and IL‑6 production were evaluated by Griess reaction and ELISA, respectively. The expression levels of inducible nitric oxide synthase (iNOS), prostaglandin E2 (PGE2), cyclooxygenase 2 (COX‑2), collagen II, matrix metalloproteinase (MMP)‑13, p65 nuclear factor (NF)‑κB and inhibitor‑κBα were detected by western blot analysis. The results indicated that CGA reversed IL‑1β‑induced increases in iNOS/NO, IL‑6, MMP‑13 and COX‑2/PGE2 production, and reversed the IL‑1β‑mediated downregulation of collagen II. In addition, the data suggested that CGA was capable of inhibiting the IL‑1β‑induced inflammatory response, at least partially via the NF‑κB signaling pathway. In conclusion, CGA may be considered a suitable candidate agent in the treatment of OA.

Adaptive support ventilation (ASV) is a closed-loop ventilation, which can make automatic adjustments in tidal volume (VT) and respiratory rate based on the minimal work of breathing. The purpose of this research was to study whether ASV can provide a protective ventilation pattern to decrease the risk of ventilator-induced lung injury in patients of acute respiratory distress syndrome (ARDS). In the clinical study, 15 ARDS patients were randomly allocated to an ASV group or a pressure-control ventilation (PCV) group. There was no significant difference in the mortality rate and respiratory parameters between these two groups, suggesting the feasible use of ASV in ARDS. In animal experiments of 18 piglets, the ASV group had a lower alveolar strain compared with the volume-control ventilation (VCV) group. The ASV group exhibited less lung injury and greater alveolar fluid clearance compared with the VCV group. Tissue analysis showed lower expression of matrix metalloproteinase 9 and higher expression of claudin-4 and occludin in the ASV group than in the VCV group. In conclusion, the ASV mode is capable of providing ventilation pattern fitting into the lung-protecting strategy, this study suggests that ASV mode may effectively reduce the risk or severity of ventilator-associated lung injury in animal models.

Objective and quantitative assessment of fundus image quality is essential for the diagnosis of retinal diseases. The major factors in fundus image quality assessment are image artifact, clarity, and field definition. Unfortunately, most of existing quality assessment methods focus on the quality of overall image, without interpretable quality feedback for real-time adjustment. Furthermore, these models are often sensitive to the specific imaging devices, and cannot generalize well under different imaging conditions. This paper presents a new multi-task domain adaptation framework to automatically assess fundus image quality. The proposed framework provides interpretable quality assessment with both quantitative scores and quality visualization for potential real-time image recapture with proper adjustment. In particular, the present approach can detect optic disc and fovea structures as landmarks, to assist the assessment through coarse-to-fine feature encoding. The framework also exploit semi-tied adversarial discriminative domain adaptation to make the model generalizable across different data sources. Experimental results demonstrated that the proposed algorithm outperforms different state-of-the-art approaches and achieves an area under the ROC curve of 0.9455 for the overall quality classification.

Synovitis is an aseptic inflammation that leads to joint effusion, pain and swelling. As one of the main drivers of pathogenesis in osteoarthritis (OA), the presence of synovitis contributes to pain, incidence and progression of OA. In our previous study, DC32 [(9α,12α-dihydroartemisinyl) bis(2'-chlorocinnmate)], a dihydroartemisinin derivative, was found to have an antirheumatic ability via immunosuppression, but the effect of DC32 on synovitis has not been fully illuminated. In this study, we chose to evaluate the effect and mechanism of DC32 on attenuating synovial inflammation. Fibroblast-like synoviocytes (FLSs) of papain-induced OA rats were isolated and cultured. And DC32 significantly inhibited the invasion and migration of cultured OA-FLSs, as well as the transcription of IL-6, IL-1β, CXCL12 and CX3CL1 in cultured OA-FLSs measured by qPCR. DC32 remarkably inhibited the activation of ERK and NF-κB pathway, increased the expression of Nrf2 and HO-1 in cultured OA-FLSs detected by western blot. DC32 inhibited the degradation and phosphorylation of IκBα which further prevented the phosphorylation of NF-κB p65 and the effect of DC32 could be relieved by siRNA for Nrf2. In papain-induced OA mice, DC32 significantly alleviated papain-induced mechanical allodynia, knee joint swelling and infiltration of inflammatory cell in synovium. DC32 upregulated the mRNA expression of Type II collagen and aggrecan, and downregulated the mRNA expression of MMP2, MMP3, MMP13 and ADAMTS-5 in the knee joints of papain-induced OA mice measured by qPCR. The level of TNF-α in the serum and secretion of TNF-α in the knee joints were also reduced by DC32 in papain-induced OA mice. In conclusion, DC32 inhibited the inflammatory response in osteoarthritic synovium through regulating Nrf2/NF-κB pathway and attenuated OA. In this way, DC32 may be a potential agent in the treatment of OA.

OBJECTIVE: To investigate the epidemiological and clinical features of cow's milk protein allergy (CMPA) in infants presenting mainly with gastrointestinal symptoms. METHODS: A retrospective analysis was performed for the clinical data of 280 hospitalized infants, who were diagnosed with CMPA presenting mainly with gastrointestinal symptoms. RESULTS: Among the 280 infants, 203 infants(72.5%) were aged of less than 6 months. Major manifestations included diarrhea in 171 infants (61.1%), hematochezia in 149 infants (53.2%), vomiting in 71 infants (25.4%), eczema in 57 infants (20.4%), malnutrition in 42 infants (15%) and constipation in 13 infants (4.6%). Of the 280 infants, 258 (92.1%) had mild-to-moderate CMPA and 22 (7.9%) had severe CMPA. Compared with the mild-to-moderate CMPA group, the severe CMPA group had a significantly higher incidence rate of malnutrition (50.0% vs 12.0%) and a signifcantly lower incidence rate of hematochezia (22.7% vs 55.8%). The breastfeeding CMPA group had signifcantly lower incidence rates of malnutrition (10.3% vs 24.6%) and severe CMPA (4.4% vs 18.0%) than the artifcial feeding CMPA group, and the artifcial feeding CMPA group had a signifcantly lower incidence rate of hematochezia than the breastfeeding and mixed feeding CMPA groups (37.7% vs 56.6%/59.0%). CONCLUSIONS: CMPA presenting mainly with gastrointestinal symptoms is more common in infants aged of less than 6 months. Diarrhea and hematochezia are the most common manifestations at the time of onset. Most infants have mild-to-moderate allergy. Compared with breastfeeding, artifcial feeding is more likely to cause malnutrition and severe CMPA.

Diabetic Retinopathy (DR) is the most common cause of avoidable vision loss, predominantly affecting the working-age population across the globe. Screening for DR, coupled with timely consultation and treatment, is a globally trusted policy to avoid vision loss. However, implementation of DR screening programs is challenging due to the scarcity of medical professionals able to screen a growing global diabetic population at risk for DR. Computer-aided disease diagnosis in retinal image analysis could provide a sustainable approach for such large-scale screening effort. The recent scientific advances in computing capacity and machine learning approaches provide an avenue for biomedical scientists to reach this goal. Aiming to advance the state-of-the-art in automatic DR diagnosis, a grand challenge on "Diabetic Retinopathy - Segmentation and Grading" was organized in conjunction with the IEEE International Symposium on Biomedical Imaging (ISBI - 2018). In this paper, we report the set-up and results of this challenge that is primarily based on Indian Diabetic Retinopathy Image Dataset (IDRiD). There were three principal sub-challenges: lesion segmentation, disease severity grading, and localization of retinal landmarks and segmentation. These multiple tasks in this challenge allow to test the generalizability of algorithms, and this is what makes it different from existing ones. It received a positive response from the scientific community with 148 submissions from 495 registrations effectively entered in this challenge. This paper outlines the challenge, its organization, the dataset used, evaluation methods and results of top-performing participating solutions. The top-performing approaches utilized a blend of clinical information, data augmentation, and an ensemble of models. These findings have the potential to enable new developments in retinal image analysis and image-based DR screening in particular.

Summary Alzheimer's disease (AD) is characterized clinically by memory loss and cognitive decline. Protein kinase A (PKA)‐CREB signaling plays a critical role in learning and memory. It is known that glucose uptake and O‐GlcNAcylation are reduced in AD brain. In this study, we found that PKA catalytic subunits (PKAcs) were posttranslationally modified by O‐linked N‐acetylglucosamine (O‐GlcNAc). O‐GlcNAcylation regulated the subcellular location of PKAcα and PKAcβ and enhanced their kinase activity. Upregulation of O‐GlcNAcylation in metabolically active rat brain slices by O‐(2‐acetamido‐2‐deoxy‐d‐glucopyranosylidenamino) N‐phenylcarbamate (PUGNAc), an inhibitor of N‐acetylglucosaminidase, increased the phosphorylation of tau at the PKA site, Ser214, but not at the non‐PKA site, Thr205. In contrast, in rat and mouse brains, downregulation of O‐GlcNAcylation caused decreases in the phosphorylation of CREB at Ser133 and of tau at Ser214, but not at Thr205. Reduction in O‐GlcNAcylation through intracerebroventricular injection of 6‐diazo‐5‐oxo‐l‐norleucine (DON), the inhibitor of glutamine fructose‐6‐phosphate amidotransferase, suppressed PKA‐CREB signaling and impaired learning and memory in mice. These results indicate that in addition to cAMP and phosphorylation, O‐GlcNAcylation is a novel mechanism that regulates PKA‐CREB signaling. Downregulation of O‐GlcNAcylation suppresses PKA‐CREB signaling and consequently causes learning and memory deficits in AD.

Early afterdepolarization (EAD) plays an important role in arrhythmogenesis. Many experimental studies have reported that Ca2+/calmodulin-dependent protein kinase II (CaMKII) and β-adrenergic signaling pathway are two important regulators. In this study, we developed a modified computational model of human ventricular myocyte to investigate the combined role of CaMKII and β-adrenergic signaling pathway on the occurrence of EADs. Our simulation results showed that (1) CaMKII overexpression facilitates EADs through the prolongation of late sodium current’s (INaL) deactivation progress; (2) the combined effect of CaMKII overexpression and activation of β-adrenergic signaling pathway further increases the risk of EADs, where EADs could occur at shorter cycle length (2000 ms versus 4000 ms) and lower rapid delayed rectifier K+ current (IKr) blockage (77% versus 85%). In summary, this study computationally demonstrated the combined role of CaMKII and β-adrenergic signaling pathway on the occurrence of EADs, which could be useful for searching for therapy strategies to treat EADs related arrhythmogenesis.

Background Coronavirus disease 2019 (COVID-19) has spread outside the initial epicenter of Wuhan. We compared cases in Guangzhou and Wuhan to illustrate potential changes in pathogenicity and epidemiological characteristics as the epidemic has progressed. Methods We studied 20 patients admitted to the Third Affiliated Hospital of Sun Yat-Sen University in Guangzhou, China from January 22 to February 12, 2020. Data were extracted from medical records. These cases were compared with the 99 cases, previously published in Lancet, from Wuhan Jinyintan Hospital from January 1 to January 20, 2020. Results Guangzhou patients were younger and had better prognosis than Wuhan patients. The Wuhan patients were more likely to be admitted to the ICU (23% vs 5%) and had a higher mortality rate (11% vs 0%). Cases in Guangzhou tended to be more community clustered. Diarrhea and vomiting were more common among Guangzhou patients and SARS-CoV-2 RNA was found in feces. Fecal SARA-CoV-2 RNA remained positive when nasopharyngeal swabs turned negative in some patients. Conclusions This study indicates possible diminishing virulence of the virus in the process of transmission. Yet persistent positive RNA in feces after negative nasopharyngeal swabs suggests a possible prolonged transmission period that challenges current quarantine practices.

Stephania species is one of the alkaloid-rich genus of the family Menispermaceae. Most plants of the genus Stephania possess medicinal value, whose main components are alkaloids. However, the non-medical species are often mistakenly used as herbs because of the difficulty in identification of the species. A systematic method which involved the combination of DNA barcoding, HPLC-QTOF-MS/MS and UHPLC was established for differentiation, chemical profiles and quality evaluation of medicinal Stephania species. Firstly, twenty batches of Stephania species samples were classified into five Stephania species by DNA barcoding. Secondly, 114 alkaloids including 22 tetrahydroprotoberberines, 13 protoberberines, 27 aporphines, 13 benzylisoquinolines, 12 hasubanans, 3 morphines and 24 other alkaloids were clearly or tentatively identified. Thirdly, thirteen representative components were simultaneously detected by UHPLC-DAD to characterize the differences of chemical compositions among five Stephania species. In conclusion, this method was comprehensive and effective for identification, chemical profiles and quality evaluation of medicinal Stephania species. It will provide a basis for holistic quality evaluation of medicinal Stephania species.

Microtubule-associated protein tau in Alzheimer’s disease (AD) brain is hyperphosphorylated, truncated, and aggregated into neurofibrillary tangles. Oligomeric and hyperphosphorylated tau (Oligo-tau) isolated from AD brain captures and templates normal tau into filaments both in vitro and in vivo; this prion-like activity is believed to be responsible for the progression of neurofibrillary pathology in AD. The 3xTg-AD mouse model develops both Aβ and tau pathologies and thus gains popularity in preclinical studies of AD. Despite the histopathological similarity of the 3xTg-AD model to AD, biochemical authenticity of tau alterations in this model remains elusive. To investigate the biochemical basis of tau pathology in 3xTg-AD brain, we here compared pathological alterations of tau in the aged 3xTg-AD brain to those in AD brain. We found that in contrast to substantial high molecular weight smear tau (HMW-tau) lacking the N-terminal portion and hyperphosphorylated at multiple sites in AD brain, tau in 3xTg-AD mouse brain showed no detectable HMW-tau or truncation but slightly increased phosphorylation when normalized with total tau. In addition, AT8 immunostaining exhibited filamentous tau inclusions in AD brain, but predominantly truffle-like morphology in aged 3xTg-AD mouse brain. Further, Oligo-tau isolated from 3xTg-AD mice showed minimal potency in capturing tau in vitro and seeding tau aggregation in cultured cells when compared to AD Oligo-tau. These findings suggest that the alterations of tau in 3xTg-AD mouse brain differ from those in AD brain. In 3xTg-AD mice, the lack of N-terminal truncation, scarce SDS/reducing reagent-resistant HMW-tau, and minimal hyperphosphorylation may collectively result in low potency in prion-like activity of the Oligo-tau.

Background Thymoma and thymic carcinoma are rare thymic epithelial tumors. We investigated the efficacy of first‐line gemcitabine and cisplatin (GP) chemotherapy versus gemcitabine and cisplatin chemotherapy combined with the anti‐angiogenic drug endostar (GP + E) in advanced thymoma and thymic carcinoma. Methods The records of 45 patients with invasive metastatic thymomas or thymic carcinomas treated with GP as first‐line therapy between August 2008 and July 2017 at the Department of Respiratory Medicine, Peking University Cancer Hospital and Institute were retrospectively reviewed. Results Eighteen patients (75%) in the GP + E group achieved a partial response and six (25%) had stable disease. In GP only group, nine (42.8%) patients achieved a partial response, 11 (52.4%) had stable disease, and one (4.8%) had progressive disease. The GP + E group had a significantly higher overall response rate (75% vs. 42.9%; P = 0.028), and median progression‐free survival (PFS) and overall survival (OS) of 19 and 76 months, respectively. In the GP only group, median PFS and OS were 16 and 29 months, respectively. PFS and OS were not significantly different between the groups. Conclusions GP has moderate efficacy and could represent a suitable first‐line therapy for thymic carcinoma and thymoma. Chemotherapy combined with endostar could improve the overall response rate, but did not prolong PFS or OS.