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In product development (PD) organizations, coordinating technical dependencies among teams with different expertise in overlapping processes is a fundamental challenge. This article takes a more sophisticated approach than prior methodologies to improve coordination via organizational clustering, by accounting for both team structural and attribute similarity from the perspective of social network analysis. We built models to quantify the impact of the overlapping processes on the interaction strength among PD teams, which we then used to construct structural similarity by combining tie strength and social cohesion among teams via the design structure matrix. To evaluate the organization network, we propose social embeddedness-related centrality indices within (intracluster) and across (intercluster) team groupings. To facilitate knowledge sharing, we base team attribute similarity on product- and process-related expertise among teams. We integrate the modularity index and an improved silhouette index to find an optimal number of clusters, which we then incorporate with team similarity measures as inputs to a spectral clustering algorithm. An industrial example illustrates the proposed model. The clustering results reinforce several managerial practices but also yield new insights, such as how to measure similarity among teams based on organizational network characteristics and how structural and attribute similarities impact the optimal organizational structure.

Background: Phase I/II clinical trials using fetal retinal pigment epithelium (fRPE), human embryonic stem cell (hESC)-derived RPE, or human induced pluripotent stem cell (hiPSC)-derived RPE as potential sources of materials for cell-based therapy to treat degenerative retinal diseases have been carried out during the past decade. Challenges for successful translational cell-based therapy include cell manufacture, cell quality, cell storage, and cell behavior in vivo. In this study, we investigated the culture-induced changes in passaged fetal RPE, hESC-RPE and hiPSC-RPE cells in vitro and explored the differentiation and maturation effect of all-trans retinoic acid (ATRA) on those RPE cells. Methods: A total of 9 fetal RPE cell lines, hESC-RPE and hiPSC-RPE cell lines were set up using previously described methods. The culture-induced changes in subsequent passages caused by manipulating plating density, dissociation method and repeated passaging were studied by microscope, real-time quantitative PCR, western blot and immunofluorescent assays. Gene and protein expression and functional characteristics of fRPE, hESC-RPE and hiPSC-RPE incubated with ATRA at different concentration were also evaluated.Results: Compared with fRPE, hESC-RPE and hiPSC-RPE showed decreased gene and protein expression of RPE markers. Passage 3 RPE of all three types seeded at a density of 6×105 and 9x105 cells/mL in basal medium maintained pigmented polygonal, cobblestone-like morphology. RPE cells underwent mesenchymal changes showing increased expression of mesenchymal markers including a-SMA, N-cadherin, fibronectin and decreased expression of RPE markers including RPE65, E-cadherin and ZO-1, as a subsequence of low plating density, inappropriate dissociated method, and repeated passaging. fRPE, hESC-RPE and iPSC-RPE treated by ATRA at different concentrations showed increased expression of RPE markers such as RPE65, bestrophin (BEST) and CRALBP, and increased expression of negative complement regulatory proteins (CRP) including complement factor H (CFH), CD46, CD55 and CD59, and increased transepithelial resistance (TER) as well.Conclusion: Although hESC and hiPSC-derived RPE are morphologically similar to fRPE, and also have the tendency to undergo epithelial-to-mesenchymal transition (EMT) changes during the culturing and passaging process in vitro, differences in protein and gene expression among three RPE types exist. Moreover, ATRA can increase RPE markers expression, as well as to increase the expression levels of CRPs gene and protein in fRPE and stem cell-derived RPE.

Major depressive disorder is the most common mental disorder with significant economic burden and limited treatments. Acupuncture has emerged as a promising non-pharmacological treatment for reducing depressive symptoms. However, the potential mechanisms and clinical effectiveness of acupuncture are not fully understood. This review aimed to: (1) summarize the available evidence on the mechanisms and clinical effectiveness of acupuncture for depression, and then (2) compare with pharmacological interventions, guiding future studies. Studies with animal models of depression and patients have shown that acupuncture could increase hippocampal and network neuroplasticity and decrease brain inflammation, potentially to alleviating depressive disorders. Overall clinical studies indicated that acupuncture could relieve primary depression, particularly milder cases, and was helpful in the management of post-stroke depression, pain-related depression, and postpartum depression both as an isolated and adjunct treatment. It was emphasized that acupuncture combined with antidepressant pharmacological treatment not only enhanced the improvement of primary and secondary depressive symptoms but also reduced the side effects of the medical treatment, which is the main cause for high dropout rates with drug treatment. In summary, substantial evidence from animal and human researches supported the beneficial effect of acupuncture in depression. However, most clinical trials of acupuncture were small, and it is unclear whether their findings can be generalized, so more studies are needed.

Reader engagement has often been explored from a metadiscourse perspective, but little research has been conducted on the variation in engagement across participants, especially readers. Based on data from a collection of 120 Chinese letters of advice from governments and hospitals produced during the COVID-19 pandemic, a cross-interactant analysis of metadiscourse is conducted in this paper, and the interactants’ impacts on reader engagement are discussed. The findings reveal that (1) both governments and hospitals utilize engagement markers, boosters, attitude markers, and frame markers more than other types of metadiscourse items; (2) differences exist in the use of metadiscourse among the issuing agencies; (3) as reader identity varies from ingroup to outgroup membership, the probability of booster use by a hospital is higher than that by a government; and (4) the likelihood of using frame, transition and attitude markers is higher for governments than for hospitals. The paper concludes by discussing different communicative styles adopted by two agencies in a crisis context.

BACKGROUND Stapedial tendon ossification is a rare disease, with only a few reports. The stapedial tendon originates from the apex of the pyramidal eminence and is attached to the neck of the stapes. In stapedial tendon ossification, the stapes is fixed, causing conductive hearing loss. In most cases, complete hearing restoration is achieved by dividing the stapedial tendon after exploratory tympanotomy. CASE SUMMARY A 28-year-old woman presented to our hospital with the major complaint of bilateral hearing loss that started during childhood. Exploratory tympanotomy was performed due to suspicion of otosclerosis or middle ear anomalies. We found bilateral conductive hearing loss due to stapedial tendon ossification with a middle ear anomaly during surgery. There have been several reports of complete recovery of hearing after resection of the stapedial tendon. However, in this case, recovery of hearing was insufficient, even with the division of the stapedial tendon. In the second surgery, the stapes anomaly and footplate fixation were confirmed, and hearing was completely recovered after stapedotomy. Therefore, we report this case with a review of the relevant literature. CONCLUSION This is the first case of stapedial tendon ossification and fixation of the footplate surgically diagnosed on both sides. With surgical treatment, successful results are expected.

This study aims to investigate the effect of eccentric load on the seismic and fracture behavior of Q235B steel members with circular hollow section (CHS). To this end, uniaxial tension and ultra-low cycle fatigue tests on both un-notched and notched Q235B steel coupon specimens were conducted first to evaluate the material’s micromechanical fracture behavior. Next, 7 full-scale Q235B CHS steel members with different global slenderness were tested under cyclic axial loads with varying eccentricities. It is observed that: (1) the increase of the eccentricity of the axial load negatively affects the seismic and fracture resistance of CHS steel members, resulting in the deterioration of the strength, stiffness, energy dissipation, and ductility; (2) Large eccentricities lead to the reduction in the fracture life of Q235B CHS steel members; and (3) High global slenderness results in the reduction in both compression bearing capacity and energy dissipation of CHS steel members. In addition to the experimental program, finite element analyses are performed to simulate the seismic and fracture behavior of CHS steel members. The results from the finite element analyses are in good agreement with those from the experiment.

STUDY OBJECTIVES: Obstructive sleep apnea (OSA) is a multilevel problematic disease. Major septal deviation (SD) can lead to severe nasal congestion, which, in turn, can lead to sleep apnea. Although SD seems to be related to OSA, very few studies have quantitatively examined this relationship. In this study, we investigate this using a 9-year large-scale cohort study. METHODS: The SD group was selected out of 1 million individuals randomly extracted by the National Health Insurance Service. The non-SD group was obtained through propensity score matching considering several variables. The primary end point was OSA diagnosis. RESULTS: The study (SD) group included 11,238 individuals and the non-SD group (control group) included 22,476 persons. The overall hazard ratio for OSA in the SD group was 4.39 (95% confidence interval [CI]: 3.56–5.42). In subgroup analysis, the hazard ratio for OSA of male individuals was 3.77 (95% CI: 2.83–5.03), high economic status was 1.27 (95% CI: 1.05–1.56), metropolitan area was 1.31 (95% CI: 1.07–1.62), young age was 0.79 (95% CI: 0.64–0.98), hypertension was 1.00 (95% CI: 0.37–2.7), and diabetes mellitus was 2.44 (95% CI: 1.15–5.21). In the SD group, the hazard ratio for OSA after septoplasty was 0.71 (95% CI: 0.54–0.94). CONCLUSIONS: From long-term follow-up, the prevalence of OSA was 4.39 times higher in the SD group compared with the control group. This phenomenon was more pronounced with increasing body mass index and decreased significantly after septoplasty. CITATION: Yeom SW, Chung SK, Lee EJ, et al. Association between septal deviation and OSA diagnoses: a nationwide 9-year follow-up cohort study. J Clin Sleep Med. 2021;17(10):2099–2106.

OBJECTIVE To explore the relationships between hepatitis B virus (HBV) DNA, HBV RNA and hepatitis B surface antigen (HBsAg) and to evaluate their predictive value for mother-to-child transmission of HBV. DESIGN An observational cohort study. SETTING First Hospital of Jilin University. POPULATION HBsAg-positive and hepatitis B e antigen (HBeAg) -positive pregnant women were recruited. METHODS Blood samples were collected from mothers before delivery, and HBV infection of infants was evaluated at 7 months of age. RESULTS Overall, 268 mothers and 271 infants were enrolled. HBV DNA and HBsAg levels were correlated (rs = 0.699; P

The absence of a temporal bone overlying the superior semicircular canal causes superior semicircular canal dehiscence (SSCD). The vestibular symptom of SSCD syndrome (SCDS) is vertigo and audiologic symptoms include autophony, hyperacusis, and ear fullness. A 52-year-old man presented with left-sided unilateral hearing loss, aural fullness, and recurrent spinning-type vertigo. He had positive Hennebert sign and mixed-type hearing loss, with a prominent low-frequency air-bone gap. These symptoms reminded us of SCDS, and computed tomography (CT) revealed SSCD. However, the patient had not experienced vertigo until 1 week prior to the visit. In addition, the audiogram revealed fluctuation of hearing, which was aggravated when the vestibular symptoms manifested. Vertigo might be due to Menière’s disease rather than SCDS and SSCD was incidentally detected on CT. According to reviews, this is no reported case of SCDS manifested as Menière’s disease, so we report this case with a brief review of the literature.

The traditional convolutional neural networks applied in mineral prospectivity mapping usually extract features from only one scale at each iteration, resulting in plain features. To combat this limitation, this study utilized a convolutional neural network based on GoogLeNet to predict prospectivity for gold deposits in the Fengxian study area, China. The GoogLeNet adopted four groups of convolution kernels to extract and integrate features from multiple scales, obtaining abundant and comprehensive features related to mineralization. According to a multi-source geoinformation analysis, we selected 11 exploration criteria, including three geological factors (NW-trending brittle-ductile faults, NE-trending brittle faults, and anticline axes) and eight geochemical exploration data layers (Au, Ag, As, Hg, Pb, Zn, Cu, and Sb). Then, we created predictor samples to train the models to mine evidential features. Following to a comprehensive analysis, we formed a fusion model of GoogLeNet for mineral prospectivity modeling. The results demonstrated that the fusion model achieved an optimized predictive accuracy of 93.1% and an area under curve of 0.968. This fusion model outperformed the other models with superior success rate and prediction area rate performances, capturing 72% of the known gold deposits in just 27.3% of the research area. The results indicate the effectiveness of GoogLeNet in mineral prospectivity mapping. Finally, we classified the Fengxian district into three areas according to their different mineral prospectivity. The high-prospectivity areas provide significant implications for further exploration of gold deposits in the study area.

The modeling and optimization of welding spots have great effects on the stiffness performance of vehicles. To improve the traditional one-dimensional linear models that may lead to severe underestimation of the strain energy of welding spots, this paper proposes a multidimensional strain energy estimation model that considers the welding spots and adjacent elements as a whole and includes three principal stress directions. The model is verified by a U-shaped sample test. Based on the model, a method for evaluating welding spot contributions is constructed and applied to a light bus to optimize the positions of the welding spots of the body-in-white (BIW). After eight iterations of optimization, with the same number of welding spots, the frequencies of the first and second modes of the BIW are improved by 5.1% and 3.4%, respectively, while the static torsional stiffness and bending stiffness are increased by 3.2% and 1.2%, respectively.

Covid-19 (Novel coronavirus pneumonia, NCP) was characterized by fever, dry cough, fatigue, greasy tongue coating and pulsating pulse. According to the literature, with those four symptoms, examination and identification, it is believed that NCP belongs to the category of “pandemic” in Chinese medicine. The main infection is dampness, infection location in triple energizer, the basic pathogenesis is characterized by “dampness, phlegm, blood stasis heat, toxin and deficiency.” According to the law of blood transfer of symptom differentiation of triple energizer and weiqi-yingxue the treatment is divided into stages, such as early stage, middle stage, severe stage and recovery stage. Most of the patients were early stage and middle stage, which were the direct transmission of the disease. A small number of patients had the reverse transmission of pericardium and the internal and external detachment. The main method of treatment is to remove infection, remove dampness and detoxify. In addition, to grasp the treatment of early stage and middle stage patients, helps to stop the disease from developing, and it is the key to reduce the criticality of the disease, as well as reduce the mortality.

Mass customization (MC) is recognized as a new manufacturing paradigm for market competition, and several empirical studies have discussed elements of organizational structure that are conducive to MC. A previous study proposed a model of quality at source and identified cultural values that can be changed by cultural artifacts, such as the stop-the-line system and the Andon system. This paper explores the impacts of three groups of MC enabler variables (personalized design, modular design, and automated processes) on two internal dimensions of organizational culture (work cooperation and relationship harmony).This paper surveyed 160 samples across five manufacturing industries. The results confirm that the three MC enablers (personalized design, modular design, and automated processes) correlate positively with two internal dimensions of the organizational culture of Chinese manufacturers (work cooperation and relationship harmony). Of the two internal dimensions, work cooperation enhances organizational performance, while relationship harmony has no impact on organizational performance. Modular design, automated processes, and work cooperation are powerful tools in the implementation of MC and organizational performance. Personalized design and relationship harmony are useful in MC. However, these tools are intermediate and limited, and they do not contribute to the general performance of the entire organization. Thus, in terms of internal- and team-oriented cultural factors, work cooperation is more important than relationship harmony in the implementation of MC. Relationship harmony is a tool for managing work atmosphere, and this is a new characteristic feature of MC as a new operational paradigm.

Background Atrial fibrillation (AF) is the most common cardiac arrhythmia in patients with chronic kidney disease (CKD) and acute coronary syndrome (ACS). This study aimed to explore the frequency and impact of AF on clinical outcomes in CKD patients with ACS. Methods CKD inpatients with ACS between November 2014 and December 2018 were included based on the improving care for cardiovascular disease in China-ACS (CCC-ACS) project. Included patients were divided into an AF group and a non-AF group according to the discharge diagnosis. Multivariable logistic regression was used to adjust for potential confounders. Results A total of 16,533 CKD patients with ACS were included. A total of 1418 (8.6%) patients had clinically recognized AF during hospitalization, 654 of whom had an eGFR of 45 to 2, and 764 had an estimated glomerular filtration rate (eGFR) 2. Compared with the non-AF group, the AF group had a higher risk of in-hospital mortality [OR 1.250; 95% CI (1.001–1.560), P = 0.049] and major adverse cardiovascular events (MACEs) [OR 1.361; 95% CI (1.197–1.547), P 2, patients with eGFR 2 had a 1.512-fold increased risk of mortality and a 1.435-fold increased risk of MACEs. Conclusions AF was a risk factor affecting the short-term prognosis of ACS patients in the CKD population. Furthermore, the lower the eGFR, the higher the risk of in-hospital mortality and MACEs in CKD patients with ACS. Trial registry: Clinicaltrial.gov, NCT02306616. Registered 29 November 2014, https://clinicaltrials.gov/ct2/show/NCT02306616?term=NCT02306616&draw=2&rank=1

BACKGROUND AND PURPOSE Restless legs syndrome (RLS) has been suggested as a prodromal symptom of Parkinson disease (PD). Olfactory or taste dysfunction can also occur preceding PD diagnosis. However, whether RLS is associated with chemosensory dysfunction remains unknown. We thus aim to investigate the association between RLS and perceived olfactory and taste dysfunction. METHODS We performed a cross-sectional analysis including 90,337 Chinese adults free of neurodegenerative diseases in the Kailuan study in 2016. Presence of RLS was defined using revised RLS diagnostic criteria or the Cambridge-Hopkins questionnaire for RLS. Perceived olfactory and taste dysfunction was collected via a questionnaire. The association between RLS and perceived olfactory and taste dysfunction was assessed using logistic regression model, adjusting for potential cofounders such as age, sex, and medical history. RESULTS RLS was associated with high odds of having perceived olfactory and/or taste dysfunction (adjusted odds ratio = 5.92, 95% confidence interval = 3.11-11.3). The significant association persisted when using the Cambridge-Hopkins questionnaire (adjusted odds ratio = 5.55, 95% confidence interval = 2.37-13.0) or when excluding participants with major chronic diseases. CONCLUSIONS RLS was associated with increased odds of perceived olfactory and taste dysfunction.

Objective This study aimed to systematically evaluate the association between triceps skinfold (TSF) thickness (which indicates subcutaneous fat) mid-arm muscle circumference (MAMC; which reflects muscle mass), mid-upper arm circumference (MUAC), and all-cause mortality. Methods A total of 17,717 adults from the China Health and Nutrition Survey (1993-2015) were included. Cox proportional hazards models were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for all-cause mortality. The joint effect of TSF thickness and MAMC was examined, and planned subgroup analyses were performed. Results The highest quartiles of TSF thickness, MAMC, and MUAC were significantly associated with low all-cause mortality, independent of BMI (TSF thickness: HR = 0.704 [95% CI: 0.575-0.862]; MAMC: HR = 0.729 [95% CI: 0.607-0.876]; MUAC: HR = 0.713 [95% CI: 0.583-0.872]). A 1-SD increase showed comparable risk reductions for TSF thickness and MAMC (14.6% and 14.0%), with 16.1% risk reductions in MUAC. There were positive additive interactions between TSF thickness and MAMC. The inverse association existed in young, middle-aged, and elderly participants (P-heterogeneity > 0.05). Conclusions Mid-arm muscle and subcutaneous fat were inversely associated with all-cause mortality, independent of BMI, beyond the elderly population. Mid-arm muscle and subcutaneous fat made comparable contributions to and had positive joint effects on all-cause mortality.

Background Behcet's disease (BD) is a chronic disease characterized by oral and vulvar ulcers as well as eye and skin damage and involves multiple systems. It presents as an alternating process of repeated attacks and remissions. Esophageal venous rupture and bleeding caused by BD is rarely reported at home and abroad. This paper reports a case of bleeding from oesophageal varices caused by BD, aiming to provide an additional dimension for considering the cause of bleeding from esophageal varices in the future. Case summary A 38-year-old female patient was admitted due to a gradual increase in shortness of breath and chest tightness after the activity, and was admitted to our hospital for treatment. After admission, relevant examinations showed that the patient had multiple blood clots. Four days after admission, she suddenly experienced massive hematemesis. Emergency esophagogastroduodenoscopy revealed bleeding from esophageal and gastric varices. The patient had no history of viral hepatitis or drinking habits, and no history of special genetic diseases or congenital vascular diseases. There is no obvious abnormality in liver function. After reviewing the medical history, it was found that the patient had recurred oral ulcers since childhood, ulcers were visible in the perineum during menstruation, and there was an intermittent red nodular rash and uveitis. The current skin acupuncture reaction is positive, combined with the evaluation of the external hospital and our hospital, the main diagnosis is BD. She received methylprednisolone, cyclophosphamide, immunomodulation, acid suppression, gastric protection, and anticoagulation and anti-infection treatments, and was discharged from the hospital. During the 1-year follow-up period, the patient did not vomit blood again. Conclusion This case highlights bleeding from esophageal varices caused by BD, aiming to provide an additional dimension concerning the cause of bleeding from esophageal varices in the future.

The new product development (PD) project is a complex network of communications involving trust relationships among teams. Trust is prominent, influencing the team positions and organizational performance indirectly. To manage the coordination complexity in PD projects, in this paper, we build a model of mutual trust among teams and further identify core teams to optimize the PD organizational network structure. First, we identified the technical interdependency and emotional closeness that influence the transmission behavior of the tie strength in the PD organizational network. Then, we examined how the presence of a common third party in the organizational network affects the trust transferability between interdependent teams. We modelled the structural similarity based on the trust transferability. To identify the core teams, which typically have high importance as well as diverse knowledge in the organizational network, we improved the LeaderRank centrality with trust transferability related to common recipients/sources to evaluate the importance of teams and present the team attributes (i.e. expertise) diversity. To build the group around core teams, we used the core teams as the input parameter (i.e. the initial clustering seeds) of the K-means clustering algorithms. The clustering results reinforce several managerial practices in an industrial example, including how trust transferability impacts the optimal organizational network structure and how to build an organizational network structure based on core teams.

Nerve root metastases are extremely rare with only a handful of cases ever reported. Metastasis to sites other than the primary site is common in malignant tumors whereas spinal ganglion metastasis is extremely rare and has been only reported in individual cases. The lumbar spine tends to be more common areas of presentation whereas breast cancer metastasis has been rarely reported. We herein reported two cases of breast carcinoma metastasis to multiple spinal nerve roots. The metastasis sites were S1 nerve root in Case 1 and left L5 and bilateral cervical nerve roots in Case 2. On magnetic resonance imaging (MRI), the nerve roots in the intervertebral foramen zones appeared thickened and contrast-enhanced MRI exhibited intense enhancement. Pathological examination showed that these primary lesions were breast cancer in both cases, and there were intracranial multiple metastases in both cases, including preoperative metastasis to multiple nerve roots (lumbar and cervical) and postoperative recurrence. The clinical course was characterized by worsening radicular symptoms—especially intractable pain. The radiologic appearance might mimic a neurogenic tumor, which is performed intervertebral foraminal area lesion, and the corresponding ganglion/nerve root became thickened and was enhanced significantly. Surgical intervention with tumor debulking followed by radiotherapy provides local tumor control and palliation from pain, but it is palliative. Therefore, for patients with radiological manifestations of radiculopathy, the possibility of metastatic tumors should be considered.

This study aimed to investigate the moment carrying behavior of typical Tibetan timber beam-column joints under monotonic vertical static load and also evaluate the influence of length ratio of Gongmu to beam (LRGB) and dowels layout on the structural performance of the joint. Six full-scale specimens were fabricated with same construction but different Gongmu length and dowels position. The moment carrying performance of beam-column joints in terms of failure mode, moment resistance, and rotational stiffness of joints were obtained via monotonic loading tests. Test results indicated that all joints are characterized by compressive failure perpendicular to grain of Ludou. Additionally, it was found that greater LRGB leads to greater initial rotational stiffness and maximum moment of the joint by an increase of restraint length for beam end; however, offsetting dowels toward column resulted smaller stiffness and ultimate bending moment of joints, particularly, offsetting Beam-Gongmu dowels toward column changed the moment-rotation curve pattern of the beam-column joint, accompanied by a hardening stiffness at last phase. Furthermore, a simplified trilinear model was proposed to represent the moment-rotation relationship of the typical Tibetan timber beam-column joint.

BACKGROUND Germinoma is a type of germ cell tumor that most frequently arises in the midline axis of the brain. Impaired vision is a clinical manifestation of germinnoma. Although rare, intracranial germinoma seeding to the perioptic arachnoid space is one cause of visual acuity decrease. CASE SUMMARY An 11yearold girl who presented with polyuria and polydipsia and subsequently developed diminution of vision. Imaging showed bilateral heterogeneous enhancement of the optic nerve sheaths and atrophy of the optic nerve, and transsphenoidal biopsy revealed a germinoma. The patient experienced poor visual recovery following chemotherapy and radiotherapy. Germinomas are rare and they are mostly identified in children and adolescents. The manifestations include diabetes insipidus, pituitary dysfunction, visual complaints, etc. The mechanisms that lead to visual loss include intracranial hypertension, compression of optic chiasma, and tumor invasion. A literature review was performed to summarize the cases with a tumor infiltrating the optic nerve. Most of the reported patients were adolescents and presented with anterior pituitary hormone deficiency. Enhancement of optic nerve sheaths and optic disc pallor could be identified in most of the cases. The purpose of this report is to provide awareness that in cases where a germinoma is associated with visual loss, though rare, perioptic meningeal seeding should be taken into consideration. CONCLUSION The case report suggests that children with diabetes insipidus need a complete differential diagnosis.

Objectives Our aim was to generalize the available evidence and evaluate the effectiveness of acupuncture for urinary incontinence in middle-aged and elderly women. Methods Six databases including VIP, CNKI, Wan Fang, Web of Science, PubMed and The Cochrane Library were systematically searched to retrieve similar studies updated to December 2019 to gather RCTs regarding the effectiveness of acupuncture for middle-aged and elderly women with urinary incontinence. Two researchers independently performed the whole process of retrieving the studies, extracting the data and assessing the risk of bias of the included studies. The current meta-analysis was performed using RevMan 5.3 software. Results A total of eight studies with 607 patients were included in the evaluation. The current meta-analysis showed that Compared with rehabilitation exercise or medication, acupuncture intervention significantly improved the clinical effectiveness (OR = 5.52, 95 % CI, 3.13–9.73), reduced the urine leakage in pad test (SMD = −2.67, 95 % CI, −4.05 to −1.29) and decrease the ICIQ-SF score (MD = −3.46, 95 % CI, −3.69 to −3.22). The results indicated that acupuncture intervention can help the patients alleviate the symptoms effectively. Conclusion Based on this study, acupuncture intervention of stress urinary incontinence in middle-aged and elderly women can improve the clinical effectiveness, reduce the urine leakage in pad test and ICIQ-SF score. More high-quality studies with large sample size are required for further verification.

Background The incidence and the risk factors of in-hospitalized acute kidney injury (AKI) in patients hospitalized for atrial fibrillation (AF) were unclear. Methods The Improving Care for Cardiovascular Disease in China-AF (CCC-AF) project is an ongoing registry and quality improvement project, with 240 hospitals recruited across China. We selected 4527 patients hospitalized for AF registered in the CCC-AF from January 2015 to January 2019. Patients were divided into the AKI and non-AKI groups according to the changes in serum creatinine levels during hospitalization. Results Among the 4527 patients, the incidence of AKI was 8.0% (361/4527). Multivariate logistic analysis results indicated that the incidence of in-hospital AKI in patients with AF on admission was 2.6 times higher than that in patients with sinus rhythm (OR 2.60, 95% CI 1.77–3.81). Age (per 10-year increase, OR 1.22, 95% CI 1.07–1.38), atrial flutter/atrial tachycardia on admission (OR 2.16, 95% CI 1.12–4.15), diuretics therapy before admission (OR 1.48, 95% CI 1.07–2.04) and baseline hemoglobin (per 20 g/L decrease, OR 1.21, 95% CI 1.10–1.32) were independent risk factors for in-hospital AKI. β blockers therapy given before admission (OR 0.67, 95% CI 0.51–0.87) and non-warfarin therapy during hospitalization (OR 0.71, 95% CI 0.53–0.96) were associated with a decreased risk of in-hospital AKI. After adjustment for confounders, in-hospital AKI was associated with a 34% increase in risk of major adverse cardiovascular (OR 1.34, 95% CI 1.02–1.90, p = 0.023). Conclusions Clinicians should pay attention to the monitoring and prevention of in-hospital AKI to improve the prognosis of patients with AF.

Manganese dioxide (MnO2) promises for high-performance asymmetric suprecapacitors, owing to its high theoretical capacity, abundant source, and low cost. However, insufficient practically-achievable capacity and relatively narrow voltage window in alkaline electrolyte are blocking high energy density of MnO2-based supercapacitors, where strategies for activating its capacitive performance and widening voltage window are the top priorities to solve the bottleneck problems. Herein, both the fiber-in-tube (NCCM-FiT) and particle-in-tube (NCCM-PiT) nanostructures coulping active NiCoOx nanoparticles and conductive carbon with MnO2 tubes have been purposely fabricated, using the electrospun nickel cobalt oxides/carbon nanofibers (NCO/CNFs) as the self-template agents for enhanced energy density of MnO2-based supercapacitors. These hierarchical hollow nanotubes with gradient pores and unique compositions yield excellent capacitive properties, in terms of a competitive capacity (431.7 F g−1 or 431.7 C g−1, 0.5 A g−1), which is 2.7 times that of the MnO2 nanotubes-based electrodes. A maximum energy density of 46.4 Wh kg−1 is obtained at the power density of 400 W kg−1 for the asymmetric device assembled with the NCCM-PiT-based positive electrode and the electrospun CNFs-based negative electrode. The remarkable energy density demonstrated by these hierarchical hollow nanotubes exemplifies a novel and effective design in electrode materials for the asymmetric supercapacitors (ASCs) with superior performance.

The ongoing COVID-19 pandemic is causing huge impact on health, life, and global economy, which is characterized by rapid spreading of SARS-CoV-2, high number of confirmed cases and a fatality/case rate worldwide reported by WHO. The most effective intervention measure will be to develop safe and effective vaccines to protect the population from the disease and limit the spread of the virus. An inactivated, whole virus vaccine candidate of SARS-CoV-2 has been developed by Wuhan Institute of Biological Products and Wuhan Institute of Virology. The low toxicity, immunogenicity, and immune persistence were investigated in preclinical studies using seven different species of animals. The results showed that the vaccine candidate was well tolerated and stimulated high levels of specific IgG and neutralizing antibodies. Low or no toxicity in three species of animals was also demonstrated in preclinical study of the vaccine candidate. Biochemical analysis of structural proteins and purity analysis were performed. The inactivated, whole virion vaccine was characterized with safe double-inactivation, no use of DNases and high purity. Dosages, boosting times, adjuvants, and immunization schedules were shown to be important for stimulating a strong humoral immune response in animals tested. Preliminary observation in ongoing phase I and II clinical trials of the vaccine candidate in Wuzhi County, Henan Province, showed that the vaccine is well tolerant. The results were characterized by very low proportion and low degree of side effects, high levels of neutralizing antibodies, and seroconversion. These results consistent with the results obtained from preclinical data on the safety.

Purpose High-sensitivity C-reactive protein (hs-CRP) has been shown as an important predictor of cardiovascular risk, and sleep duration is an important factor influencing health outcomes. However, the association between hs-CRP and sleep duration among Chinese adults remained unknown and controversial. We aimed to explore the associations between sleep duration and hs-CRP levels among Chinese adults, and the differences in sex and geographical regions. Methods This cross-sectional study was based on nationally representative Chinese samples from the 2009 China Health and Nutrition Survey, which employed multistage, random cluster designs. Habitual sleep duration was self-reported with short and long sleep duration defined as ≤6h and ≥9h per day, respectively. Participants were divided into 4 groups based on the categories of self-reported sleep duration (≤6h, 7h, 8h, ≥9h per day), excluding hs-CRP levels ≥10 mg/L. Subset samples were stratified by sex and geographical regions. Results A total of 8170 Chinese adults with a mean age of 50.0±14.9 years and 4369 (53.5%) men were included. Participants sleeping eight hours had the lowest hs-CRP levels. Long sleep duration (≥9h) was significantly associated with elevated hs-CRP levels after adjusting for multiple covariates in full samples (β=0.0356; 95% CI: 0.0050-0.0663; P=0.0228), but the associations of short sleep duration (≤ 6h) were limited to the unadjusted model. Long sleep duration was associated with elevated hs-CRP levels in women (β= 0.0512; 95% CI: 0.0097-0.0927; P=0.0155) and in the northern region of China (β=0.0699; 95% CI: 0.0210-0.1187; P=0.0051), but not in men or the southern region. Conclusion Long but not short sleep duration was positively associated with elevated hs-CRP levels, independent from traditional risk factors among Chinese adults, and sex and geographical differences were observed. Our findings imply that modifications of long sleep duration might be added to behavioral therapy to reduce cardiovascular risk in Chinese adults.

AIM: To provide a detailed description of the natural history of persistent subretinal fluid (SRF) after successful repair of rhegmatogenous retinal detachment (RRD) and its association with visual outcome. METHODS: This was a prospective long-term follow-up for eyes undergoing scleral buckling (SB) surgery for macula-off RRD. Examinations were carried out preoperatively and postoperatively at 1, 3, 6, 9 and 12mo, until persistent SRF had completely resolved. One month postoperatively, optical coherence tomography (OCT) was used to classify SRF into three patterns: bleb-like loculated (BL), shallow-diffused (SD), and multiple blebs (MB). Serial OCT imaging was used to evaluate morphological changes in SRF until its complete disappearance. Patients were divided into two groups depending on the presence or absence of persistent SRF. RESULTS: A total of 59 patients (59 eyes) were included. There were no statistical differences between two groups at baseline, except for the proportion of patients with high myopia and a younger age. One month after surgery, OCT detected persistent SRF in 49 eyes (83.1%). The 3 morphological patterns of SRF were observed in 27 eyes (55.1%) with BL, 13 eyes (26.5%) with SD, and 9 eyes (18.4%) with MB. The mean time for complete absorption differed significantly across the three SRF patterns (F=8.097, P=0.001), which was 8.8±6.1, 20.1±12.1, and 16.7±10.2mo in BL, SD, and MB, respectively. In 9 of the 13 eyes with SD, the pattern transformed into MB type. In cases involving MB, the size and number of blebs decreased gradually until they had been completely absorbed. Eyes with persistent SRF were more likely to demonstrate disruption of the ellipsoid zone (49.0% vs 10%, P=0.034). The final best-corrected visual acuity of two groups was 0.37±0.11 (with SRF) vs 0.34±0.12 (without SRF) logMAR (P=0.499), respectively. CONCLUSION: High preoperative myopia and younger age are associated with persistent SRF. BL is the most commonly observed pattern with the shortest duration and gradually disappeared. Most cases involving SD SRF transform into MB type during resolution. The size and number of the MBs decrease gradually until they were completely absorbed. The absence of persistent SRF may contribute to slow visual recovery in the short-term but does not influence the final visual outcome.

Purpose Anisodine hydrobromide (Ani) is isolated from the medicinal plant Anisodus tanguticus (Maxim.) Pascher for clinical use. Although considerable research regarding Ani has been reported, the safety profiles of Ani are currently unknown. This study investigated the cardiorespiratory effects of Ani in conscious dogs to provide clinicians a detailed safety profile of Ani on the cardiorespiratory system. Materials and Methods Using the Latin square design, the study was divided into six phases, where in each phase, six telemetered beagle dogs received one dose of normal saline or sotalol hydrochloride or Ani (0.1, 0.4, 1.6, or 6.4 mg/kg). Electrocardiogram, blood pressure (BP) and respiratory parameters were collected before and after administration for 24 hours. Statistical comparisons were performed at scheduled time-points. Results The heart rate was significantly increased, PR and QTCV intervals were significantly shortened in Ani 0.4, 1.6, 6.4 mg/kg treatment group after drug administration. Compared with the saline group, a significant increase in heart rate and shortening of PR, QTCV intervals were observed in the Ani 1.6, 6.4 mg/kg treatment groups from 5 min to 4 h time-points. Diastolic and mean BP were significantly increased in Ani 1.6, 6.4 mg/kg from 1 h to 2 h time-points compared to those of the saline control. Accelerated breathing was observed in the first 20 min after Ani 0.4, 1.6, and 6.4 mg/kg treatment, although not statistically significant. Furthermore, no significant differences were observed in any of the corresponding indexes of Ani 0.1 mg/kg treatment group at different time-points compared to those of the saline group. Conclusion Ani may have adverse effects on the cardio-respiratory systems of dogs at doses above 0.4 mg/kg, whereas Ani 0.1 mg/kg was devoid of potentially deleterious effects on cardiorespiratory function.

Objective To summarize the research progress of music therapy in hospice care and to provide reference for further research. Methods A wide range of literatures on music therapy and hospice care at home and abroad were searched and read, and the literature was integrated, judged, analyzed, and summarized. Results The related research on music therapy in hospice care mainly focused on western developed countries such as Europe and the United States. China is still in the stage of theoretical exploration, lacking qualitative research based on case investigation and empirical research based on data statistics. Conclusions Music therapy supports the management of symptoms in hospice care, which can meet the diverse needs of patients and their family members including physical, psychological, social, and spiritual.

Introduction Simultaneous administration of acetylsalicylic acid (ASA) and clopidogrel has demonstrated efficacy in the treatment of acute coronary syndrome. Clopidogrel + ASA in a fixed-dose combination (FDC) provides a pharmaceutical option to enhance adherence to the coadministration of dual antiplatelet therapy (DAPT). Herein, we evaluate the bioequivalence of enteric ASA and clopidogrel in an FDC compared with simultaneous administration of the individual formulations. Methods This study is a randomized, single-center, open-label, three-sequence, three-period, two-treatment, crossover study conducted in healthy Chinese male and female subjects under fed conditions. Subjects were randomized to receive, in each period, a single dose of (1) a combination tablet containing 75-mg clopidogrel and 100-mg enteric ASA (test formulation) or (2) coadministration of one 75-mg clopidogrel tablet and one 100-mg enteric-coated ASA tablet (reference formulations) under fed conditions. Plasma samples were analyzed for ASA, salicylic acid, clopidogrel, and the clopidogrel metabolite SR26334. For ASA, the reference-scaled average bioequivalence (RSABE) analysis was conducted for Cmax of ASA because within-subject standard deviation (SDW) was ≥ 0.294 for log-transformed Cmax. Results The point estimate (test/reference geometric mean ratio) was between 0.80 and 1.25, and the upper one-sided 95% confidence interval (CI) for the scaled average bioequivalence metric was ≤ 0 (-0.08). AUC of ASA as SDW was

Background: In this study, we aimed to investigate the dynamic changes of lipid profile under double filtration plasmapheresis (DFPP) in severe hypertriglyceridemia-induced acute pancreatitis (sHTGP) patients and ascertain whether these changes were associated with the prognosis of the disease.Methods: This retrospective study was conducted at a tertiary critical care center in China. We included sHTGP patients who were admitted within 72h after AP onset. All the sHTGP patients received DFPP within 24h after admission. Lipid profile changes was measured in 47 patients with sHTGP on admission, consecutive 4 days after DFPP and at discharge. According to the TG levels in the first day after DFPP, we divided patients into two group: non-target (TG>5.6mmol/L) and target group (TG ≤5.6mmol/L). Propensity score matching was used to investigate association between TG-lowering effect and the prognosis. Linear regression analysis on four models was used to determine the relationship between other lipid parameters and the outcome.Results: Except for low density lipoprotein, all the parameters of lipid profile at disease onset showed significant difference from their normal levels. The median serum triglyceride (TG) level of the sHTGP patients was 42.9 mmol/L on admission. In the first day after DFPP, serum TG, cholesterol (TC) and very low density lipoprotein decreased significantly, and the high-density lipoprotein (HDL) as well as apoprotein A1 increased meanwhile. TG continued to fall for the following three days and the other indicators held steady. After propensity score matching, the hospitalization duration was significantly lower in the target group (14.5 [13.0, 16.0] vs 8.0 [6.0, 15.3], P=0.035). Linear regression analysis revealed that the levels of HDL were negatively associated with the duration of hospitalization in three adjusted models.Conclusion: There was distinct fluctuation of the lipid profile upon the burst of sHTGP and the parameters changed significantly in the first day after DFPP. Among these parameters, HDL may serve as a biomarker for disease prognosis in patients with sHTGP. Moreover, reaching the TG-lowering target of 5.6mmol/L may shorten hospitalization duration.

AIM To study the involvement and interrelationship of epithelial cell adhesion molecule (EpCAM) and epithelial-mesenchymal transition (EMT) in endometriosis. METHODS Samples from 114 patients undergoing endometrial biopsy or operation for endometriosis and 23 premenopausal women undergoing endometrial biopsy for non-endometriotic benign disease. Immunohistochemistry was used to detect expression level of EpCAM, E-cadherin and N-cadherin in endometrium from patients with (n = 24) and without endometriosis (n = 23), and in lesions from bowel (n = 46), peritoneal (n = 20) and ovarian (n = 24) endometriosis. RESULTS There was no significant difference in the expression level of EpCAM, E-cadherin and N-cadherin, respectively, between endometrium from women with and without endometriosis (P > 0.05). There was also no significant difference in the expression level of EpCAM, E-cadherin and N-cadherin, respectively, among lesions from the bowel, peritoneal and ovarian endometriosis (P > 0.05). We found that the immunoreactivity of endometriotic epithelial cells to EpCAM and N-cadherin was significantly higher than that of eutopic endometrium, but decreased to E-cadherin (P

Objective To examine the results of raloxifene for prevention of periprosthetic bone loss around the femoral stem in patients undergoing total hip arthroplasty (THA). Methods Between January 2015 and May 2017, 240 female patients between 55 and 80 years underwent primary THA and were randomly allocated to receive 60 mg raloxifene hydrochloride per day (treatment group, TG, n = 120) or placebo (control group, CG, n = 120) orally at bedtime using computer‐generated randomization sequence generation. Baseline data, the Western Ontario McMaster Universities Osteoarthritis Index (WOMAC), women's quality of life (QoL) score, bone mineral density (BMD) around the prosthesis, and adverse events were compared between the two groups. The measuring range of BMD around the prosthesis was divided into seven regions of interest (ROI). The sample size was calculated to detect a mean difference in BMD of 0.15 g/cm2 with a standard deviation (SD) of 0.3. The error was set at 0.05 and the power level at 90% with additional compensation for a possible dropout rate of 20%. Results A total of 240 participants in the study up to 24 months after THA. There were no significant differences in the mean BMD of all the zones between groups before surgery (all P > 0.05). However, there were significant differences in the BMD of Gruen zones 4 and 7 between groups at 6 months postoperatively (both P 0.05), but did show decreased odds of breast cancer in comparison with those using a placebo (P = 0.0437). Conclusion Raloxifene can help inhibit bone loss around the prosthesis and improve the QoL of postmenopausal women after THA with no increased adverse events, and can even decrease the odds of breast cancer.

Objective: Vitrification prevents ice formation within the high concentration of cryoprotectant agents and allows the cells and extracellular milieu to solidify into a glass-like state. This study aimed to provide objective information on the available data regarding singleton births comparing embryo vitrification with fresh embryo transfers. Methods: PubMed and Cochrane databases were searched for studies conducted up to 2017. Low birth weight (LBW), very low birth weight (VLBW), preterm birth (PTB), very PTB, small for gestational age (SGA), large for gestational age, perinatal mortality, cesarean section, and preeclampsia were measured. Results: The search returned 220 articles, and 13 of these met the inclusion criteria. A significantly lower risk of SGA birth was observed in the vitrified embryo transfer group than in the fresh transfer group. Conversely, a higher risk of very PTB, VLBW, large size for gestational age, and perinatal mortality was observed more frequently in the vitrified embryo transfer group. Conclusions: Vitrified embryo transfer was associated with the improved outcome of neonates regarding the SGA rate compared with fresh embryo transfer, but included a higher risk of very PTB, VLBW, large size for gestational age, and perinatal mortality. Caution should be exercised in interpreting these findings given the low level of evidence of the studies.

Drugs that induce thrombosis in the tumour vasculature have not resulted in long-term tumour eradication owing to tumour regrowth from tissue in the surviving rim of the tumour, where tumour cells can derive nutrients from adjacent non-tumoral blood vessels and tissues. Here, we report the performance of a combination of tumour-infarction therapy and chemotherapy, delivered via chitosan-based nanoparticles decorated with a tumour-homing peptide targeting fibrin-fibronectin complexes overexpressed on tumour-vessel walls and in tumour stroma, and encapsulating the coagulation-inducing protease thrombin and the chemotherapeutic doxorubicin. Systemic administration of the nanoparticles into mice and rabbits bearing subcutaneous or orthotopic tumours resulted in higher tumour growth suppression and decreased tumour recurrence than nanoparticles delivering only thrombin or doxorubicin, with histological and haematological analyses indicating an absence of detectable toxicity. The co-administration of a cytotoxic payload and a protease to elicit vascular infarction in tumours with biodegradable tumour-targeted nanoparticles represents a promising strategy for improving the therapeutic index of coagulation-based tumour therapy.

The study aimed to assess whether caesarean section and nonbreastfeeding can prevent mother-to-child transmission (MTCT) in HBsAg- and HBeAg-positive mothers via a cohort study and a meta-analysis. (1) Pregnant women who were positive for HBsAg and HBeAg and did not receive antiviral treatment during pregnancy were recruited from the First Hospital of Jilin University, Maternal and Child Health Care Center of Jiangsu and Henan from August 2009 to June 2015. Infants received active and passive immunity. (2) In addition, a systematic literature search was performed in the PubMed, Embase, Cochrane, China National Knowledge Infrastructure and Wanfang Chinese databases. The retrieval strategy was [("HBV" or "hepatitis b" or "hepatitis b virus") and ("mother-to-infant transmission" or "vertical transmission")]. Studies were screened, and data were extracted. The fixed-effect model was used to analyse the studies. A total of 852 mothers and 857 newborns were enrolled. At the age of 7 months, 41 infants (4.78%) were positive for HBsAg. Multivariate analysis showed that mothers with higher HBV DNA levels (>108 IU/mL; RR = 3.03, 95% CI: 1.41-6.52) were associated with an increased risk of infection. Although there was no statistical significance, caesarean section (RR = 0.61) and nonbreastfeeding (RR = 0.88) showed a tendency to reduce the risk of infection. (2) A total of 5726 studies were identified. Together with our study, 13 were included in the analysis of delivery mode, and 12 were included in the analysis of feeding mode. The risk of infection in the caesarean section group was lower than that in the vaginal delivery group (RR = 0.58, 95% CI: 0.46-0.74). In the analysis of feeding mode, the risk in the nonbreastfeeding group was significantly lower (RR = 0.74, 95% CI: 0.56-0.98). In conclusion, caesarean section and nonbreastfeeding reduced the risk of MTCT in infants of HBsAg- and HBeAg-positive mothers who did not receive antiviral therapy during pregnancy.

BACKGROUND Many patients with major depressive disorder (MDD) have been found to have psychotic symptoms. However, few studies have reported the prevalence of comorbid psychotic symptoms in first-episode drug naive (FEDN) MDD patients. This study was to investigate the prevalence of psychotic symptoms and related risk factors in a large sample size of FEDN MDD patients in a Chinese population. METHODS A total of 573 patients with diagnosis of MDD at their first episode were recruited with their demographic and clinical data. Positive scale of the Positive and Negative Syndrome Scale was utilized for psychotic symptoms, Hamilton Anxiety Rating Scale (HAMA) for anxiety symptoms, and Hamilton Depression Rating Scale (HAMD) for depressive symptoms. RESULTS The prevalence of psychotic symptoms in these MDD patients was 9.8%. MDD patients with psychotic symptoms had significantly higher HAMD and HAMA total scores than those without psychotic symptoms (both p

Introduction Dual antiplatelet therapy, aspirin and a P2Y12 inhibitor, is recommended to prevent thrombotic complications of acute coronary syndrome. Clopidogrel plus acetylsalicylic acid combination is the most commonly used dual antiplatelet therapy recommended by international guidelines and in Chinese clinical practice. Poor adherence to dual antiplatelet therapy or premature interruption of dual antiplatelet therapy is an important contributor to cardiovascular mortality and lethal cardiovascular events. Clopidogrel + acetylsalicylic acid fixed-dose combination enhances adherence to dual antiplatelet therapy. Herein, we aimed to evaluate bioequivalence of acetylsalicylic acid and clopidogrel in fixed-dose combination compared with simultaneous administration of their individual formulations in healthy Chinese subjects under fasting conditions. Methods This was a randomized, single-center, open-label, three-sequence, three-period, two-treatment, crossover study with a washout period of 10 days conducted in healthy Chinese volunteers. Subjects were randomized to receive Co-Plavix® (test formulation- fixed-dose combination of 100 mg acetylsalicylic acid and 75 mg clopidogrel) once and reference formulations (coadministration of individual formulations of 100 mg acetylsalicylic acid and 75 mg clopidogrel) twice during the study period. Pharmacokinetic parameters were analyzed for acetylsalicylic acid, its metabolite salicylic acid, clopidogrel, and its metabolite SR26334. As acetylsalicylic acid shows high intrasubject variability, the reference-scaled average bioequivalence (RSABE) approach was implemented for acetylsalicylic acid analysis, while bioequivalence of clopidogrel was assessed using the average bioequivalence method. Point ratios and confidence intervals (CIs) for AUC, AUClast, and Cmax for acetylsalicylic acid and clopidogrel were calculated. Results In total, 171 healthy subjects were enrolled in this study. Subjects were randomized and 170 subjects were treated with test or reference formulation; 164 subjects completed the study. Regarding acetylsalicylic acid exposure, as reference within-subject standard deviation (SDW) was at least 0.294 for acetylsalicylic acid Cmax, AUClast, and AUC, the RSABE analysis method was used to assess bioequivalence for all three parameters. The point estimates were within the 0.80–1.25 range (1.19, 1.09, and 1.04, respectively), and upper one-sided 95% CIs of scaled average bioequivalence metric were at most 0 (− 0.30, − 0.14, and − 0.10, respectively). Thus, bioequivalence was demonstrated with acetylsalicylic acid. Bioequivalence was also achieved with clopidogrel as the 90% CIs for geometric mean ratios of clopidogrel Cmax, AUClast, and AUC were within the bioequivalence range (0.80–1.25). Conclusion Application of the reference-scaled average bioequivalence approach to evaluate bioequivalence of acetylsalicylic acid in Chinese male and female healthy volunteers under fasting conditions demonstrated bioequivalence of test and reference formulations. Trial Registration CTR20181695. Electronic supplementary material The online version of this article (10.1007/s12325-020-01369-z) contains supplementary material, which is available to authorized users.

This study was aimed to develop and conduct an Omaha system-based continuing nursing program for chronic kidney disease (CKD) patients undergoing peritoneal dialysis (PD) and to explore its effect on patients’ nutritional status. A randomized controlled trial was performed in a teaching hospital in China between June 2017 and July 2018. A total of 203 eligible patients were included and then randomly assigned to the study group (n = 101) or the control group (n = 102). In the study group, health education, treatments and procedures, case management, and surveillance based on the Omaha system were used. In the control group, only common outpatient nursing intervention was given to the patients. Changes in subjective global assessment (SGA), anthropometric measurements including body mass index (BMI), triceps skin-fold thickness (TSF), mid-arm muscle circumference (MAMC), and handgrip strength (HGS), and biochemical parameters (hemoglobin, albumin, pre-albumin, total cholesterol, and creatinine) were evaluated before the intervention and 6 months after the intervention and differences in measurements were analyzed. After intervention, the proportion of well-nourished patients in the study group was significantly improved from 6.19 to 29.90% ($$\chi$$2 = 18.441, P

Infection remains the most significant complication of ventriculoperitoneal shunt (VPS) surgery. The objective of this study was to investigate intracranial infections complicating VPS surgery in adults with hydrocephalus. Patients who underwent VPS surgery for hydrocephalus between 2000 and 2016 were included. Clinical data and follow-up evaluations were examined and analysed retrospectively. A total of 502 patients with hydrocephalus who underwent VPS surgery were included. They were followed up for at least 2 years. Twelve patients with incomplete data were excluded. Four hundred and ninety patients were included in the final analysis. Twenty-five cases of intracranial infection occurred, accounting for 5.1% of patients with VPS surgery. The mean age of the patients was 57.1 ± 10.1 years (range, 39-72 years). The incidence of intracranial infection in patients over 60 years of age was higher than that in patients under 60 years of age (P = .007). Age (P = .007), diabetes (P = .026), skin infection (P = .028), bed-ridden (P = .007), and modified operation (P = .011) were highly correlated with the incidence of intracranial infection. The findings of this retrospective study show that age, diabetes, skin infection, bed-ridden, and modified operation of hydrocephalus significantly and independently correlated with the incidence of infection. Prospective studies are needed to assess the relationship between the incidence of infection and risk factors in patients with hydrocephalus after VPS.

Background Ondansetron, a widely prescribed antiemetic, has been implicated in drug-induced long QT syndrome. Recent patch clamp experiments have shown that ondansetron inhibits the apamin-sensitive small conductance calcium-activated potassium current (IKAS). Objective The purpose of this study was to determine whether ondansetron causes action potential duration (APD) prolongation by IKAS inhibition. Methods Optical mapping was performed in rabbit hearts with pacing-induced heart failure (HF) and in normal hearts before and after ondansetron (100 nM) infusion. APD at 80% repolarization (APD80) and arrhythmia inducibility were determined. Additional studies with ondansetron were performed in normal hearts perfused with hypokalemic Tyrode's (2.4 mM) solution before or after apamin administration. Results The corrected QT interval in HF was 326 ms (95% confidence interval [CI] 306–347 ms) at baseline and 364 ms (95% CI 351–378 ms) after ondansetron infusion (P Conclusion Ondansetron is a specific IKAS blocker at therapeutic concentrations. Ondansetron may prolong the QT interval in HF by inhibiting small conductance calcium-activated potassium channels, which increases the vulnerability to ventricular arrhythmias.

Background: Atorvastatin belongs to the group of statins and is the leading drug for hypercholesterolemia treatment. Although, its anticancer effects are highly appreciated, its properties are still unclear. The aim of this study was to explore the underlying anticancer mechanisms induced by atorvastatin and enlarge the potential target in non-small cell lung cancer. Methods: arget genes of atorvastatin were collected by the DrugBank database. Prediction of interaction between primary targets and secondary targets was performed, and protein-protein interaction network was constructed though the STRING. Then, KEGG pathway enrichment analysis was performed with WebGestalt and ClueGO, including the pathways in non-small cell lung cancer. Furthermore, a genomic alteration analysis of the selected seed genes of atorvastatin benefit and non-small cell lung cancer pathway was conducted by cBioPortal. Finally, a survival analysis with the selected seed genes in lung cancer (lung adenocarcinoma, lung squamous cell carcinoma) was conducted using Kaplan-Meier (KM) plotter. Results: To identify seed genes, 65 potential candidate genes were screened as targets for atorvastatin using STRING with DrugBank database, while the KEGG pathway was enriched to get the overlap match of pathways in non-small cell lung cancer. Then 4 seed genes, Epidermal Growth Factor Receptor (EGFR), erb-b2 receptor tyrosine kinase 2 (ERBB2), AKT serine/threonine kinase 1 (AKT1) and tumor protein p53 (TP53), were selected and their genomic alternation were evaluated by cBioPortal. Survival analysis found that TP53 and EGFR showed a significant correlation (log rank P = 3e-07 and 0.023) with lung adenocarcinoma and lung squamous cell carcinoma, according to the KM analysis. Conclusion: Gene-phenotype connectivity for atorvastatin in non-small cell lung cancer was identified using functional/activity network analysis method, and our findings demonstrated that TP53 and EGFR could be the potential targets in cancer patients with atorvastatin therapy.

Background: The statistical association between a short-term rise in low-density lipoprotein cholesterol (LDL-C) levels and the short-term outcome of acute ischemic stroke remains unknown. We aimed to evaluate the association in acute ischemic stroke patients during hospitalization. Methods: Patients with acute ischemic stroke who received statin at discharge were enrolled in this multicenter registry study. LDL-C values were measured on the first day after admission and on the day before discharge to determine the rise in LDL-C levels. Poor outcome was defined as a modified Ranking Scale score ≥2 at discharge. The National Institutes of Health Stroke Scale increase from admission to discharge by 2 points was defined as clinical deterioration. Logistic regression analyses were used to analyze the relationship between LDL-C rise during hospitalization and poor outcome at discharge. Variables that were significantly different between the LDL-C rise and LDL-C fall groups were considered in adjustment for confounding variables in model 1. Age, sex, and those variables in model 1 were considered in adjustment for confounding variables in model 2. Results: Among the 676 patients, 110 (16.3%) showed a rise in LDL-C levels during hospitalization. Multivariate analyses showed that LDL-C at admission p < 0.001). There were significantly more patients with a poor outcome in the “LDL-C rise” group than in the “LDL-fall” group (p = 0.002). Multiple models consistently showed that LDL-C rise increased the risk of a poor outcome at discharge in model 1 (OR [95% CI] 1.351 [1.059–1.723], p = 0.016) and model 2 (OR [95% CI] 1.370 [1.071–1.751], p = 0.012). LDL-C rise also increased the risk of clinical deterioration, although its p value only was 0.043 in model 1 and 0.048 in model 2. Conclusions: Rise in LDL-C during hospitalization from acute ischemic stroke is an independent predictor of poor outcome at discharge. In particular, patients with lower LDL-C values at admission are a higher at risk, and LDL-C in these patients should thus be monitored while in hospital.

Dynamic changes of RNA and antibodies in SARS-CoV-2 infected patients remain largely unknown, and influence factors for antibody production have not been fully clarified. In this study, consecutive throat swabs specimens (n = 1875) from 187 patients were collected to analyse the dynamic changes of RNA. Moreover, 162 serial serum samples from 31 patients were tested for seroconversion of IgM and IgG. Meanwhile, IgM and IgG were also detected in 409 COVID-19 patients and 389 controls. Additionally, the logistic regression analysis was executed to identify the possible influence factors for antibody production. The median positive conversion time for RNA was day 7 (IQR, 3–11), and the positive rate was highest in day 1–5 (74.59 %) and then gradually decreased. The median time of seroconversion for IgM and IgG were both day 12 (IQR, 10–15). The sensitivity and specificity for IgM (or IgG) was 87.04% and 96.92%, respectively. Multivariate logistic regression indicated that reduced lymphocytes and short positive conversion time for SARS-CoV-2 RNA were independent factors for negative results of IgM and IgG. In conclusion, RNA and antibodies should be combined for COVID-19 diagnosis, and delayed seroconversion was influenced by the decreased lymphocytes and short positive conversion time for RNA.

Although dyslipidemia commonly occurs in patients with acute promyelocytic leukemia (APL) in response to anti-APL therapy, the underlying mechanism and the lipid statuses of patients with newly diagnosed APL remain to be addressed. Methods: We conducted a retrospective study to investigate the lipid profiles of APL patients. PML-RARα transgenic mice and APL cells-transplanted mice were used to assess the effects of APL cells on the blood/liver lipid levels. Subsequently, gene set enrichment analysis, western blot and dual luciferase reporter assay were performed to examine the role and mechanism of PML-RARα and TRIB3 in lipid metabolism regulation in APL patients at pretreatment and after induction therapy. Results: APL patients exhibited a higher prevalence of dyslipidemia before anti-APL therapy based on a retrospective study. Furthermore, APL cells caused secretion of triglycerides, cholesterol, and PCSK9 from hepatocytes and degradation of low-density lipoprotein receptors in hepatocytes, which elevated the lipid levels in APL cell-transplanted mice and Pml-Rarα transgenic mice. Mechanistically, pseudokinase TRIB3 interacted with PML-RARα to inhibit PPARγ activity by interfering with the interaction of PPARγ and RXR and promoting PPARγ degradation. Thus, reduced PPARγ activity in APL cells decreased leptin but increased resistin expression, causing lipid metabolism disorder in hepatocytes and subsequent dyslipidemia in mice. Although arsenic/ATRA therapy degraded PML-RARα and restored PPARγ expression, it exacerbated dyslipidemia in APL patients. The elevated TRIB3 expression in response to arsenic/ATRA therapy suppressed PPARγ activity by disrupting the PPARγ/RXR dimer, which resulted in dyslipidemia in APL patients undergoing therapy. Indeed, the PPAR activator not only enhanced the anti-APL effects of arsenic/ATRA by suppressing TRIB3 expression but also reduced therapy-induced dyslipidemia in APL patients. Conclusion: Our work reveals the critical role of the PML-RARα/PPARγ/TRIB3 axis in the development of dyslipidemia in APL patients, potentially conferring a rationale for combining ATRA/arsenic with the PPAR activator for APL treatment.

Background Mitochondrial transcription termination factor 3 (MTERF3) is a negative regulator of mitochondrial transcription. It is a modular factor involves in mitochondrial ribosome biogenesis and protein synthesis. However, the association between MTERF3 and breast cancers remains largely unknown. The aim of this study was to investigate the expression of MTERF3 in breast carcinoma and to analyze its clinicopathological significance, and to examine the potential prognostic value of MTERF3 in breast cancer. Methods The protein expression levels of MTERF3 in MCF7 (Luminal A), BT-474 (Luminal B), SKBR3 (HER2 overexpression), MDA-MB-468 (Basal like) and MCF10A cell lines were detected by Western blotting. Immunohistochemistry (IHC), Western blotting, and semiquantitative RT-PCR were performed to analyze the protein and mRNA expression levels of MTERF3 in 58 breast cancer tissues and 58 noncancerous breast tissues. The MTERF3 expression data and clinical information from breast cancer patients were downloaded from the TCGA dataset by using the R3.6.1 software. Then the relationship between the expression level of MTERF3 and clinicopathological characteristics and the prognostic value was analyzed. A Cox regression model was performed for the multivariate analysis of the factors that affected the prognosis of breast cancer. The association between the expression levels of MTERF3 and other mitochondrial regulatory genes was analyzed with GEPIA. Results MTERF3 is upregulated in breast cancer cell lines compared to noncancerous breast cell line. The IHC results showed that the MTERF3 protein was located in the cytoplasm, and the rate of positive expression in breast cancer tissue was significantly upregulated compared with the adjacent normal tissue. The mRNA and protein expression levels of MTERF3 in breast cancer tissues were significantly higher than that in breast tissues. Moreover, the expression of MTERF3 was significantly correlated with ER status, PR status, breast cancer molecular typing, cancer type, histological diagnosis and primary site (P

The existence of gaps between tenon and mortise in traditional timber structures is very common. Accurate estimation of its probability distribution is essential for the stress and reliability analysis. This paper presents the probability distributions for the horizontal and vertical gaps based on measurement. The gap data were collected from four traditional timber buildings in a heritage building complex by manual on-site measurement. Statistical analysis of data for each building was performed. Results show that the statistical features of all four buildings are similar. All the measured gap data were then categorized into two groups in horizontal and vertical directions. The optimal distribution to represent these gap data was obtained using the probability plot correlation coefficient method and Anderson–Darling test. Results demonstrate that the Weibull distribution is the most appropriate model for fitting both the horizontal and vertical gaps. Parameters of the distributions were obtained from the maximum likelihood estimate. A finite-element (FE) numerical investigation for a joint was conducted. Gaps were randomly created using the obtained probability model in the joints. Static analysis results show that the gaps will weaken the mechanical behavior of the tenon–mortise joint, especially the initial stiffness. Compared with the horizontal gaps, the vertical gaps affect the mechanical properties of the joint more directly.

The existence of breast cancer stem cells (BCSCs) is a major reason underlying cancer metastasis and recurrence after chemotherapy and radiotherapy. Targeting BCSCs may ameliorate breast cancer relapse and therapy resistance. Here we report that expression of the pseudokinase Tribble 3 (TRIB3) positively associates with breast cancer stemness and progression. Elevated TRIB3 expression supports BCSCs by interacting with AKT to interfere with the FOXO1-AKT interaction and suppress FOXO1 phosphorylation, ubiquitination, and degradation by E3 ligases SKP2 and NEDD4L. The accumulated FOXO1 promotes transcriptional expression of SOX2, a transcriptional factor for cancer stemness, which in turn, activates FOXO1 transcription and forms a positive regulatory loop. Disturbing the TRIB3-AKT interaction suppresses BCSCs by accelerating FOXO1 degradation and reducing SOX2 expression in mouse models of breast cancer. Our study provides insights into breast cancer development and confers a potential therapeutic strategy against TRIB3-overexpressed breast cancer., Cancer stem cells contribute to breast cancer metastasis and recurrence. Here the authors show that TRIB3 enhances breast cancer stemness through interaction with AKT to promote FOXO1 stability, which then increases SOX2 activity.