The bibliometric analysis of studies on intracytoplasmic sperm injection from 2002 to 2021.

Background: Infertility is estimated to occur in 1 out of every 4-7 couples. Intracytoplasmic sperm injection (ICSI), a type of assisted reproduction introduced in 1992, has been used across the world for almost all indications of infertility, yielding high pregnancy rates. There is a growing concern worldwide about ICSI since semen quality has declined in recent years, accompanied with the potential risks of this technology. This study aims to analyze the current status and hotspots of ICSI via a bibliometric analysis. Methods: We retrieved publications on ICSI from the Web of Science Core Collection database from 2002 to 2021. CiteSpace was used to summarize knowledge mapping of subject categories, keywords, and co-citation relationships with the strongest citation bursts. VOSviewer was used to explore co-citation and co-occurrence relationships for countries, organizations, references, authors, and keywords. Results: A total of 8271 publications were analyzed between 2002 and 2021. The major findings are as follows: the USA, China, Italy, Japan, and Belgium are the top five prolific countries. The Free University of Brussels, University of Copenhagen, University of Valencia, Ghent University, and the University of California San Francisco are the top five contributing organizations. Fertility and Sterility and Human Reproduction are the most productive and cited journals. The hotspot topics are risks of ICSI, oocyte preservation, live birth rate, infertile men, and embryo quality in the past two decades. Conclusion: This study presents a research overview of ICSI from different perspectives. These findings will contribute to a better understanding of the current status of ICSI research and provide hotspots and trends for future studies.

Proteomic and phosphoproteomic characteristics of the cortex, hippocampus, thalamus, lung, and kidney in COVID-19-infected female K18-hACE2 mice

Background Neurological damage caused by coronavirus disease 2019 (COVID-19) has attracted increasing attention. Recently, through autopsies of patients with COVID-19, the direct identification of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in their central nervous system (CNS) has been reported, indicating that SARS-CoV-2 might directly attack the CNS. The need to prevent COVID-19-induced severe injuries and potential sequelae is urgent, requiring the elucidation of large-scale molecular mechanisms in vivo. Methods In this study, we performed liquid chromatography-mass spectrometry-based proteomic and phosphoproteomic analyses of the cortex, hippocampus, thalamus, lungs, and kidneys of SARS-CoV-2-infected K18-hACE2 female mice. We then performed comprehensive bioinformatic analyses, including differential analyses, functional enrichment, and kinase prediction, to identify key molecules involved in COVID-19. Findings We found that the cortex had higher viral loads than did the lungs, and the kidneys did not have SARS-COV-2. After SARS-CoV-2 infection, RIG-I-associated virus recognition, antigen processing and presentation, and complement and coagulation cascades were activated to different degrees in all five organs, especially the lungs. The infected cortex exhibited disorders of multiple organelles and biological processes, including dysregulated spliceosome, ribosome, peroxisome, proteasome, endosome, and mitochondrial oxidative respiratory chain. The hippocampus and thalamus had fewer disorders than did the cortex;however, hyperphosphorylation of Mapt/Tau, which may contribute to neurodegenerative diseases, such as Alzheimer's disease, was found in all three brain regions. Moreover, SARS-CoV-2-induced elevation of human angiotensin-converting enzyme 2 (hACE2) was observed in the lungs and kidneys, but not in the three brain regions. Although the virus was not detected, the kidneys expressed high levels of hACE2 and exhibited obvious functional dysregulation after infection. This indicates that SARS-CoV-2 can cause tissue infections or damage via complicated routes. Thus, the treatment of COVID-19 requires a multipronged approach. Interpretation This study provides observations and in vivo datasets for COVID-19-associated proteomic and phosphoproteomic alterations in multiple organs, especially cerebral tissues, of K18-hACE2 mice. In mature drug databases, the differentially expressed proteins and predicted kinases in this study can be used as baits to identify candidate therapeutic drugs for COVID-19. This study can serve as a solid resource for the scientific community. The data in this manuscript will serve as a starting point for future research on COVID-19-associated encephalopathy. Funding This study was supported by grants from the 10.13039/501100005150Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences, the 10.13039/501100001809National Natural Science Foundation of China, and the 10.13039/501100004826Natural Science Foundation of Beijing.

Proteomic and phosphoproteomic characteristics of the cortex, hippocampus, thalamus, lung, and kidney in COVID-19-infected female K18-hACE2 mice.

BACKGROUND: Neurological damage caused by coronavirus disease 2019 (COVID-19) has attracted increasing attention. Recently, through autopsies of patients with COVID-19, the direct identification of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in their central nervous system (CNS) has been reported, indicating that SARS-CoV-2 might directly attack the CNS. The need to prevent COVID-19-induced severe injuries and potential sequelae is urgent, requiring the elucidation of large-scale molecular mechanisms in vivo. METHODS: In this study, we performed liquid chromatography-mass spectrometry-based proteomic and phosphoproteomic analyses of the cortex, hippocampus, thalamus, lungs, and kidneys of SARS-CoV-2-infected K18-hACE2 female mice. We then performed comprehensive bioinformatic analyses, including differential analyses, functional enrichment, and kinase prediction, to identify key molecules involved in COVID-19. FINDINGS: We found that the cortex had higher viral loads than did the lungs, and the kidneys did not have SARS-COV-2. After SARS-CoV-2 infection, RIG-I-associated virus recognition, antigen processing and presentation, and complement and coagulation cascades were activated to different degrees in all five organs, especially the lungs. The infected cortex exhibited disorders of multiple organelles and biological processes, including dysregulated spliceosome, ribosome, peroxisome, proteasome, endosome, and mitochondrial oxidative respiratory chain. The hippocampus and thalamus had fewer disorders than did the cortex; however, hyperphosphorylation of Mapt/Tau, which may contribute to neurodegenerative diseases, such as Alzheimer's disease, was found in all three brain regions. Moreover, SARS-CoV-2-induced elevation of human angiotensin-converting enzyme 2 (hACE2) was observed in the lungs and kidneys, but not in the three brain regions. Although the virus was not detected, the kidneys expressed high levels of hACE2 and exhibited obvious functional dysregulation after infection. This indicates that SARS-CoV-2 can cause tissue infections or damage via complicated routes. Thus, the treatment of COVID-19 requires a multipronged approach. INTERPRETATION: This study provides observations and in vivo datasets for COVID-19-associated proteomic and phosphoproteomic alterations in multiple organs, especially cerebral tissues, of K18-hACE2 mice. In mature drug databases, the differentially expressed proteins and predicted kinases in this study can be used as baits to identify candidate therapeutic drugs for COVID-19. This study can serve as a solid resource for the scientific community. The data in this manuscript will serve as a starting point for future research on COVID-19-associated encephalopathy. FUNDING: This study was supported by grants from the Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences, the National Natural Science Foundation of China, and the Natural Science Foundation of Beijing.

Constructing big data prevention and control model for public health emergencies in China: A grounded theory study.

Big data technology plays an important role in the prevention and control of public health emergencies such as the COVID-19 pandemic. Current studies on model construction, such as SIR infectious disease model, 4R crisis management model, etc., have put forward decision-making suggestions from different perspectives, which also provide a reference basis for the research in this paper. This paper conducts an exploratory study on the construction of a big data prevention and control model for public health emergencies by using the grounded theory, a qualitative research method, with literature, policies, and regulations as research samples, and makes a grounded analysis through three-level coding and saturation test. Main results are as follows: (1) The three elements of data layer, subject layer, and application layer play a prominent role in the digital prevention and control practice of epidemic in China and constitute the basic framework of the "DSA" model. (2) The "DSA" model integrates cross-industry, cross-region, and cross-domain epidemic data into one system framework, effectively solving the disadvantages of fragmentation caused by "information island". (3) The "DSA" model analyzes the differences in information needs of different subjects during an outbreak and summarizes several collaborative approaches to promote resource sharing and cooperative governance. (4) The "DSA" model analyzes the specific application scenarios of big data technology in different stages of epidemic development, effectively responding to the disconnection between current technological development and realistic needs.

Evaluation and Obstacle Analysis of Emergency Response Capability in China.

Emergency response capability evaluation is an essential means to strengthen emergency response capacity-building and improve the level of government administration. Based on the whole life cycle of emergency management, the emergency capability evaluation index system is constructed from four aspects: prevention and emergency preparedness, monitoring and early warning, emergency response and rescue, and recovery and reconstruction. Firstly, the entropy method is applied to measure the emergency response capability level of 31 Chinese provinces from 2011 to 2020. Second, the Theil index and ESDA (Exploratory Spatial Data Analysis) are applied in exploring the regional differences and spatial-temporal distribution characteristics of China's emergency response capacity. Finally, the obstacle degree model is used to explore the obstacle factors and obstacle degrees that affect the emergency response capability. The results show that: (1) The average value of China's emergency response capacity is 0.277, with a steady growth trend and a gradient distribution of "high in the east, low in the west, and average in center and northeast" in the four major regions. (2) From the perspective of spatial distribution characteristics, the unbalanced regional development leads to the obvious aggregation effect of "high-efficiency aggregation and low-efficiency aggregation", and the interaction of the "centripetal effect" and "centrifugal effect" finally forms the spatial clustering result of emergency response capability level in China. (3) Examining the source of regional differences, inter-regional differences are the decisive factor affecting the overall differences in emergency response capability, and the inter-regional differences show a reciprocating fluctuation of narrowing-widening-narrowing from 2011 to 2020. (4) Main obstacles restricting the improvement of China's emergency response capabilities are "the business volume of postal and telecommunication services per capita", "the daily disposal capacity of city sewage" and "the general public budget revenue by region". The extent of the obstacles' impacts in 2020 are 12.19%, 7.48%, and 7.08%, respectively. Based on the evaluation results, the following countermeasures are proposed: to realize the balance of each stage of emergency management during the holistic process; to strengthen emergency coordination and balanced regional development; and to implement precise measures to make up for the shortcomings of emergency response capabilities.

The Beneficial Role of Auricular Point Pressure in Insomnia and Anxiety in Isolated COVID-19 Patients.

BACKGROUND: Coronavirus disease 2019 (COVID-19) causes psychological distress and can have a negative impact on the general mental health and rehabilitation in affected patients under currently implemented isolation guidelines. Auricular point pressure (APP) as well-established technique in traditional Chinese medicine may help to relieve sleep disturbance and anxiety in COVID-19 patients. METHODS: During the early phase of the epidemic/pandemic, patients were enrolled in this study (02/2020 until 03/2020 n = 84). They were strictly isolated on specific wards at the Hubei Provincial Hospital of Integrated Chinese and Western Medicine in Hubei. The retrospective cohort study design included two groups. Group A patients were treated with an auricular point pressure (APP) in addition to standard intensive care medicine while Group B participants (No-APP) received routine nursing measures alone. Treatment outcome was measured using the St. Mary's Hospital Sleep Questionnaire (SMH) Score and the 7-Item Generalized Anxiety Disorder Scale (GAD-7). Both scores were measured in each patient at baseline and on the discharge day. RESULTS: The SMH score and sleep status changed in APP patients at the end of the treatment period when compared with No-APP patients (P < 0.01). APP-treated patients demonstrated lower GAD-7 scores than No-APP controls (P < 0.01). Further, no significant differences in safety or adverse events between the APP and No-APP groups were observed. CONCLUSION: The results from our snapshot study during the early phase of the SARS-CoV-2 epidemic/pandemic suggest that auricular point pressure could be a simple and effective tool to relieve insomnia and situational anxiety in hospitalized patients suffering from COVID-19 and kept under disconcerting conditions of isolation.

Difference in Risk Factors Associated with Acute Respiratory Distress Syndrome and Intubation/Death in Patients with Coronavirus Disease 2019: A Two-hospital Retrospective Cohort Study in Hubei, China (preprint)

Background: The reviews on the risk factors with ARDS and the worse outcomes concluded lacking robust data of risk factors to prevent COVID-19 and identified an urgent need for large sample and high-quality research in this area, as well as the features of the ARDS.Methods: This retrospective cohort study included 333 COVID-19 inpatients at two hospitals in Hubei of China in 2020. The COVID-19-related ARDS was diagnosed according to the Berlin criteria. The outcomes were ARDS development and the intubation or in-hospital death. The cox proportional hazard ratio (HR) models were employed to determine the significant risk factors. Results: The median number of days from symptom onset to ARDS diagnosis was 11.0 (IQR, 8.0–13.0). Up to 84.1% COVID-19-related ARDS patients demonstrated multiple organ injuries. The mortality rates were 41.9% and 85.7% in moderate and severe ARDS. The survival patients on invasive mechanical ventilation (IMV) had been intubated earlier since ARDS diagnosis than those who had not survived (5.5 median days, IQR 4.0-7.0 days versus 11.5 median days, IQR 6.0-14.0 days, P < 0.001). Males and all abnormal laboratory indices associated with the higher risk of ARDS (P<0.05) but were not linked with the risk of intubation or death (P>0.05). The sensitivity analyses found that lymphocyte count of < 1000 per mm3 at hospital admission were still significantly associated with developing ARDS when adjusting for age and male gender (HR, 4.10; 95% CI, 2.40-7.10), and oxygenation index (OI) ratio < 150 were more likely to predict the intubation/death after age adjustment (HR, 2.50; 95% CI, 1.17-5.30). Conclusion: The SARS-CoV-2-caused ARDS was not the typical ARDS according to Berlin criteria. The alive patients with IMV had been intubated earlier since ARDS diagnosis than those who had not survived. We identified male gender and abnormal laboratory indices associated with the ARDS but were not linked with the intubation/death. Sensitivity analysis concluded lymphocyte count of < 1000 per mm3 could predict ARDS while OI ratio less than 150 could predict intubation/death.

Clinical Characteristics and Outcomes of Patients with Coronavirus Disease 2019-associated ARDS and the Early Intubation: A Two-Hospital Retrospective Cohort Study in Hubei, China (preprint)

Background: More evidence in understanding the heterogeneity of COVID-19-associated acute respiratory distress syndrome (ARDS) and in improving strategy to increase the survival from the critical patients intubated is always needed. The study aimed to comprehensively explore the features of COVID-19-associated ARDS and the features and outcomes between the early and late intubation groups. Methods: This retrospective cohort included 65 adult COVID-19 inpatients with ARDS at two hospitals in Hubei, China. The ARDS in these patients was diagnosed according to the Berlin criteria. We defined intubation within 7 days of ARDS diagnosis as ‘early’ intubation and that performed from the eighth day as ‘late’ intubation based on literatures. The outcomes were invasive mechanical ventilation and in-hospital death. The log-binomial regression models were used to explore the risk factors and the Kaplan-Meier statistic was used to estimate the risk of mortality. Results: The median number of days from symptom onset to ARDS diagnosis was 11.0 (IQR, 8.0–13.0). Up to 84.1% COVID-19-related ARDS patients demonstrated multiple organ injuries. The mortality rates were 41.9% and 85.7% in moderate and severe ARDS. The early intubation and the late intubation had the differences in days from symptom onset/hospital admission/ARDS diagnosis to intubation (P = 0.023, P = 0.011, P < 0.001). Compared with the early-intubation group, the late-intubation group showed less severity at admission (median oxygenation index 159.0 95% CI 134.0-203.0 vs. 133.9 95% CI 98.3-183.2), but required more aggressive therapies (ICU 80% vs. 70%, CRRT 50% vs. 10%, prone-position 50% vs. 30%, and ECMO 50% vs. 10%) and had higher risk to die at hospital (RR, 3.18; 95% CI 1.98-5.12). Conclusion: The ARDS caused by COVID-19 was not typical ARDS due to prolonged onset time, multiple organ injuries, and higher mortalities. The late-intubation group showed less severity at admission but higher risk of in-hospital death than the early-intubation group. 

Antibody Detection and Dynamic Characteristics in Patients With Coronavirus Disease 2019.

BACKGROUND: The coronavirus disease 2019 (COVID-19), caused by infection with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has been rapidly spreading nationwide and abroad. A serologic test to identify antibody dynamics and response to SARS-CoV-2 was developed. METHODS: The antibodies against SARS-CoV-2 were detected by an enzyme-linked immunosorbent assay based on the recombinant nucleocapsid protein of SARS-CoV-2 in patients with confirmed or suspected COVID-19 at 3-40 days after symptom onset. The gold standard for COVID-19 diagnosis was nucleic acid testing for SARS-CoV-2 by real-time reverse-transcription polymerase chain reaction (rRT-PCR). The serodiagnostic power of the specific immunoglobulin M (IgM) and immunoglobulin G (IgG) antibodies against SARS-CoV-2 was investigated in terms of sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and consistency rate. RESULTS: The seroconversion of specific IgM and IgG antibodies were observed as early as the fourth day after symptom onset. In the patients with confirmed COVID-19, sensitivity, specificity, PPV, NPV, and consistency rate of IgM were 77.3% (51/66), 100%, 100%, 80.0%, and 88.1%, respectively, and those of IgG were 83.3% (55/66), 95.0%, 94.8%, 83.8%, and 88.9%. In patients with suspected COVID-19, sensitivity, specificity, PPV, NPV, and consistency rate of IgM were 87.5% (21/24), 100%, 100%, 95.2%, and 96.4%, respectively, and those of IgG were 70.8% (17/24), 96.6%, 85.0%, 89.1%, and 88.1%. Both antibodies performed well in serodiagnosis for COVID-19 and rely on great specificity. CONCLUSIONS: The antibodies against SARS-CoV-2 can be detected in the middle and later stages of the illness. Antibody detection may play an important role in the diagnosis of COVID-19 as a complementary approach to viral nucleic acid assays.

Coronavirus disease 2019 (COVID-19) in pregnancy: 2 case reports on maternal and neonatal outcomes in Yichang city, Hubei Province, China.

RATIONALE: The outbreak of coronavirus disease 2019 (COVID-19) in 2019 has become a global pandemic. It is not known whether the disease is associated with a higher risk of infection in pregnant women or whether intrauterine vertical transmission can occur. We report 2 cases of pregnant women diagnosed with COVID-19. PATIENT CONCERNS: In all of Yichang city from January 20, 2020, to April 9, 2020, only 2 pregnant women, who were in the late stage of pregnancy, were diagnosed with COVID-19; one patient was admitted for fever with limb asthenia, and the other patient was admitted for abnormal chest computed tomography results. DIAGNOSES: Both pregnant women were diagnosed with COVID-19. INTERVENTIONS: After the medical staff prepared for isolation and protection, the 2 pregnant women quickly underwent cesarean sections. A series of tests, such as laboratory, imaging, and SARS-CoV-2 nucleic acid examinations, were performed on the 2 women with COVID-19 and their newborns. OUTCOMES: One of the 2 infected pregnant women had severe COVID-19, and the other had mild disease. Both babies were delivered by cesarean section. Both of the women with COVID-19 worsened 3 to 6 days after delivery. Chest computed tomography suggested that the lesions due to SARS-CoV-2 infection increased. These women began to exhibit fever or reduced blood oxygen saturation again. One of the 2 newborns was born prematurely, and the other was born at full term. Neither infant was infected with COVID-19, but both had increased prothrombin time and fibrinogen, lactate dehydrogenase, phosphocreatine kinase, and creatine kinase isoenzyme contents. LESSONS: SARS-CoV-2 infection was not found in the newborns born to the 2 pregnant women with COVID-19, but transient coagulation dysfunction and myocardial damage occurred in the 2 newborns. Effective management strategies for pregnant women with COVID-19 will help to control the outbreak of COVID-19 among pregnant women.

SARS-CoV-2 turned positive in a discharged patient with COVID-19 arouses concern regarding the present standards for discharge.

An outbreak of coronavirus disease (COVID-19) in Wuhan, China caused by SARS-CoV-2 has led to a serious epidemic in China and other countries, resulting in worldwide concern. With active efforts of prevention and control, more and more patients are being discharged. However, how to manage these patients normatively is still challenging. This paper reports an asymptomatic discharged patient with COVID-19 who retested positive for SARS-CoV-2, which arouses concern regarding the present discharge standards of COVID-19.

Managing the IVF laboratory during a pandemic: international perspectives from laboratory managers.

Fertility societies worldwide responded to the COVID-19 pandemic by recommending that fertility clinics close, or sharply reduce, the clinical operation, leading to a shift in the management of IVF laboratories in three phases: shutdown preparation; maintenance during shutdown; and restart. Each of these phases carries distinct risks that need identification and mitigation, forcing laboratory managers to rethink and adapt their procedures in response to the pandemic. The sudden and unprecedented nature of the pandemic forced laboratory managers from around the world to base decisions on opinion and experience when evidence-based response options were unavailable. These perspectives on pandemic response were presented during a virtual international symposium on COVID-19, held on 3 April 2020, and organized by the London Laboratory Managers' Group. Laboratory managers from seven different countries at different stages of the pandemic (China, Italy, Spain, France, UK, Brazil and Australia) presented their personal experiences to a select audience of experienced laboratory managers from 19 different countries. The intention of this paper is to collect the learnings and considerations from this group of laboratory managers who collaborated to share personal experiences to contribute to the debate surrounding what constitutes good IVF laboratory practice in extraordinary circumstances, such as the COVID-19 pandemic.

Mitigating the Impact of COVID-19 on Emergency Stroke Care in Western China (preprint)

Background: The COVID-19 epidemic is still continuing. Little is known about the effects on stroke care. This study aims to investigate the impact of COVID-19 epidemic on urgent stroke treatment in a tertiary stroke center in western China, and to provide reference points for stroke treatment strategies during public health emergencies. Methods: The retrospective, population-based study was conducted in West China Hospital of Sichuan University, the largest hospital in the southwest of China in COVID-19 period (Dec 1, 2019 to Mar 11, 2020) and baseline non-COVID-19 period (Dec 1, 2018 to Mar 11, 2019). The COVID-19 period was further divided into pre- and peak-epidemic stages defined using government data. Medical practice was strictly based on hospital contingency plans and national expert consensus. We compared emergency visits and efficiency of stroke treatment for the baseline and COVID-19 periods. A subgroup analysis was then conducted between pre-and peak-epidemic stages. Findings: Compared with the baseline data, we found no differences in time to deliver acute interventions, intravenous thrombolysis rate (IVT), and neurological improvements in the whole COVID-19 period. There were significant reductions in visits (38·9%, p<0·0001), admission within six hours from onset (13·2%, p=0·001), mild stroke admissions (15·3%, p=0·006) and increases in rates of mechanical thrombectomy (24·4%, p<0·0001) and excellent outcome (18·1%, p<0·01). We observed significantly higher rate of IVT (17·1%, p=0·04) and shorter time to computed tomography scan (22%, p=0·01), during the peak-epidemic stages in subgroup analysis. Interpretation: The hospital’s capacity to deliver high quality stroke emergency care was hardly be affected as a result of comprehensive measures being implemented.The results provide some key messages for the practice of stroke emergency care during a crisis. Funding Statement: National Key R&D Program of China (2018YFC1311400 and 2018YFC1311401).Declaration of Interests: Authors declare no competing interests.Ethics Approval Statement: The study and analysis plan was approved by the ethical review board in West China Hospital of Sichuan University (2019/319). Written informed consent was waived.

Quadruple therapy for asymptomatic COVID-19 infection patients.

INTRODUCTION: The novel coronavirus (COVID-19) is currently in epidemic stage. After large-scale interpersonal infection, asymptomatic patients appear. Whether asymptomatic patients are contagious or not and whether they need medication are the arguments among clinical experts. AREAS COVERED: This paper reports a special asymptomatic couple with COVID-19, of which the male patient is an intercity bus driver but has not induced confirmed infection of his 188 passengers. The patients were treated with four combinations of lopinavir/ritonavir tablets, arbidol tablets, Lianhuaqingwen granules, and recombinant human interferon-α2b (IFN-α2b) injection via aerosol. Their clinical characteristics and medication were summarized and analyzed. EXPERT OPINION: The two asymptomatic patients far away from Wuhan did not seem to be highly contagious. They improved obviously, after treatment with the quadruple therapy, but the effective drug is still unknown. It should be noted that lopinavir/ritonavir tablets have many drug interactions and are the most likely drugs to cause hyperlipidemia and hyperglycemia in these two patients. IFN-α2b is more effective in the early stage of virus infection. Arbidol instruction dose may not be sufficient to inhibit the novel coronavirus in vivo. The evidence-based medicine of Lianhuaqingwen granules for treating various viral infections is just based on Chinese patients.