Identification of potential influencing factors associated with elimination of migraine headache in patients with PFO after percutaneous closure / 中华心血管病杂志

Objective: To recognize the potential factors that contribute to the eradication of migraine headache in patients with patent foramen ovale (PFO) at one year after percutaneous closure. Methods: A prospective cohort study was conducted, which enrolled patients diagnosed with migraines and PFO at the Department of Structural Heart Disease, First Affiliated Hospital of Xi'an Jiaotong University between May 2016 and May 2018. The patients were segregated into two groups based on their response to treatment, and one group showed elimination of migraines while another did not. Elimination of migraines was defined as a Migraine Disability Assessment Score (MIDAS) score of 0 at one year postoperatively. Least Absolute Shrinkage and Selection Operator (LASSO) regression model was utilized to identify the predictive variables for migraine elimination post-PFO closure. Multiple logistic regression analysis was employed to determine the independent predictive factors. Results: The study enrolled a total of 247 patients, with an average age of (37.5±13.6) years, comprising 81 male individuals (32.8%). One year after closure, 148 patients (59.9%) reported eradication of their migraines. Multivariate logistic regression analysis revealed that migraine with or without aura (OR=0.003 9, 95%CI 0.000 2-0.058 7, P=0.000 18), a history of antiplatelet medication use (OR=0.088 2, 95%CI 0.013 7-0.319 3, P=0.001 48) and resting right-to-left shunt (RLS) (OR=6.883 6, 95%CI 3.769 2-13.548 0, P<0.001) were identified as independent predictive factors for elimination of migraine. Conclusion: Migraine with or without aura, a history of antiplatelet medication use, and resting RLS are the independent prognostic factors associated with elimination of migraine. These results provide important clues for clinicians to choose the optimal treatment plan for PFO patients. However, further studies are needed to confirm these findings.

Flavonoids from the roots and rhizomes of Sophoratonkinensis and their in vitro anti-SARS-CoV-2 activity / 中国天然药物

Acute respiratory infection caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) had caused a global pandemic since 2019, and posed a serious threat to global health security. Traditional Chinese medicine (TCM) has played an indispensable role in the battle against the epidemic. Many components originated from TCMs were found to inhibit the production of SARS-CoV-2 3C-like protease (3CLpro) and papain-like protease (PLpro), which are two promising therapeutic targets to inhibit SARS-CoV-2. This study describes a systematic investigation of the roots and rhizomes of Sophora tonkinensis, which results in the characterization of 12 new flavonoids, including seven prenylated flavanones (1-7), one prenylated flavonol (8), two prenylated chalcones (9-10), one isoflavanone (11), and one isoflavan dimer (12), together with 43 known compounds (13-55). Their structures including the absolute configurations were elucidated by comprehensive analysis of MS, 1D and 2D NMR data, and time-dependent density functional theory electronic circular dichroism (TDDFT ECD) calculations. Compounds 12 and 51 exhibited inhibitory effects against SARS-CoV-2 3CLpro with IC50 values of 34.89 and 19.88 μmol·L-1, repectively while compounds 9, 43 and 47 exhibited inhibitory effects against PLpro with IC50 values of 32.67, 79.38, and 16.74 μmol·L-1, respectively.

Structural and functional characteristics of SARS-CoV-2 Omicron subvariant BA.2 spike

The Omicron subvariant BA.2 has become the dominant circulating strain of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in many countries. We have characterized structural, functional and antigenic properties of the full-length BA.2 spike (S) protein and compared replication of the authentic virus in cell culture and animal model with previously prevalent variants. BA.2 S can fuse membranes more efficiently than Omicron BA.1, mainly due to lack of a BA.1-specific mutation that may retard the receptor engagement, but still less efficiently than other variants. Both BA.1 and BA.2 viruses replicated substantially faster in animal lungs than the early G614 (B.1) strain in the absence of pre-existing immunity, possibly explaining the increased transmissibility despite their functionally compromised spikes. As in BA.1, mutations in the BA.2 S remodel its antigenic surfaces leading to strong resistance to neutralizing antibodies. These results suggest that both immune evasion and replicative advantage may contribute to the heightened transmissibility for the Omicron subvariants.

Analysis on repetitive reporting of hepatitis B in Fujian province, 2016-2020 / 中华流行病学杂志

Objective: To analyze the repetitive reporting of hepatitis B in Fujian province during 2016-2020, and provide evidence for the improvement of hepatitis B surveillance. Methods: The reporting cards from the China Information System for Disease Control and Prevention were collected and divided into repetitive reporting cards and non-repetitive reporting cards from the report cards collected according to the valid ID number on the cards, and the proportion of repetitive report cards and related factors were analyzed by using software SAS 9.4. Results: A total of 314 551 hepatitis B reporting cards were submitted in Fujian from 2016 to 2020, in which 90.93% (286 020/314 551) were included in the analysis. The repetitive reporting cards accounted for 10.48% (29 982/286 020). The annual proportion of the repetitive reporting cards from 2016 to 2020 was between 2.98% and 3.71%, showing an overall increasing trend year by year (Z=2.26, P=0.024). The proportions of the repetitive reporting cards in 1-5 years were 3.17%, 5.40%, 7.74%, 9.27% and 10.48%, respectively, showing an increase trend with year (Z=128.16, P<0.001). The proportions of the repetitive reporting cards in 10 areas of Fujian ranged from 5.44% to 13.48% with significant difference (χ2=2 050.41, P<0.001) and increased with the increase of reported incidence of hepatitis B (Z=26.92, P<0.001). There were significant differences in relationships between repetitive reporting proportion and sex, age and type of the cases between the areas with high incidence and low incidence of hepatitis B. Conclusions: The reported incidence of hepatitis B was seriously affected by the repetitive reporting in Fujian from 2016 to 2020. A cross-year and cross-area surveillance mechanism for hepatitis B should be established and targeted measures should be taken to strengthen the control of the repetitive reporting and improve the surveillance for hepatitis B.

Camel nanobodies broadly neutralize SARS-CoV-2 variants

With the emergence of SARS-CoV-2 variants, there is urgent need to develop broadly neutralizing antibodies. Here, we isolate two VHH nanobodies (7A3 and 8A2) from dromedary camels by phage display, which have high affinity for the receptor-binding domain (RBD) and broad neutralization activities against SARS-CoV-2 and its emerging variants. Cryo-EM complex structures reveal that 8A2 binds the RBD in its up mode and 7A3 inhibits receptor binding by uniquely targeting a highly conserved and deeply buried site in the spike regardless of the RBD conformational state. 7A3 at a dose of [≥]5 mg/kg efficiently protects K18-hACE2 transgenic mice from the lethal challenge of B.1.351 or B.1.617.2, suggesting that the nanobody has promising therapeutic potentials to curb the COVID-19 surge with emerging SARS-CoV-2 variants. One-Sentence SummaryDromedary camel (Camelus dromedarius) VHH phage libraries were built for isolation of the nanobodies that broadly neutralize SARS-CoV-2 variants.

Mitoxantrone modulates a glycosaminoglycan-spike complex to inhibit SARS-CoV-2 infection

Spike-mediated entry of SARS-CoV-2 into human airway epithelial cells is an attractive therapeutic target for COVID-19. In addition to protein receptors, the SARS-CoV-2 spike (S) protein also interacts with heparan sulfate, a negatively charged glycosaminoglycan (GAG) attached to certain membrane proteins on the cell surface. This interaction facilitates the engagement of spike with a downstream receptor to promote viral entry. Here, we show that Mitoxantrone, an FDA-approved topoisomerase inhibitor, targets a spike-GAG complex to compromise the fusogenic function of spike in viral entry. As a single agent, Mitoxantrone inhibits the infection of an authentic SARS-CoV-2 strain in a cell-based model and in human lung EpiAirway 3D tissues. Gene expression profiling supports the plasma membrane as a major target of Mitoxantrone but also underscores an undesired activity targeting nucleosome dynamics. We propose that Mitoxantrone analogs bearing similar GAG-binding activities but with reduced affinity for DNA topoisomerase may offer an alternative therapy to overcome breakthrough infections in the post-vaccine era.

B.1.1.7 and B.1.351 variants are highly virulent in K18-ACE2 transgenic mice and show different pathogenic patterns from early SARS-CoV-2 strains

SARS-CoV-2 continues to circulate globally resulting in emergence of several variants of concern (VOC), including B.1.1.7 and B.1.351 that show increased transmissibility and enhanced resistance to antibody neutralization. In a K18-hACE2 transgenic mouse model, we demonstrate that Both B.1.1.7 and B.1.351 are 100 times more lethal than the original SARS-CoV-2 bearing 614D. Mice infected with B.1.1.7 and B.1.351 exhibited more severe lesions in internal organs than those infected with early SARS-CoV-2 strains bearing 614D or 614G. Infection of B.1.1.7 and B.1.351 also results in distinct tissue-specific cytokine signatures, significant D-dimer depositions in vital organs and less pulmonary hypoxia signaling before death as compared to the mice infected with early SARS-CoV-2 strains. However, K18-hACE2 mice with the pre-existing immunity from prior infection or immunization were resistant to the lethal reinfection of B.1.1.7 or B.1.351, despite having reduced neutralization titers against these VOC. Our study reveals distinguishing pathogenic patterns of B.1.1.7 and B.1.351 variants from those early SARS-CoV-2 strains in K18-hACE2 mice, which will help to inform potential medical interventions for combatting COVID-19.

SARS-CoV-2 show no infectivity at later stages in a prolonged COVID-19 patient despite positivity in RNA testing

Inpatient COVID-19 cases present enormous costs to patients and health systems. Many hospitalized patients may still test COVID-19 positive, even after resolution of symptoms. Thus, a pressing concern for clinicians is the safety of discharging these asymptomatic patients if they have any remaining infectivity. This case report explores the viral viability in a patient with persistent COVID-19 over the course of a two-month hospitalization. Positive nasopharyngeal swab samples, analyzed by quantitative reverse transcription polymerase chain reactions (qRT-PCR), were collected and isolated in the laboratory, and infectious doses were analyzed throughout the hospitalization period. The patient experienced waning symptoms by hospital day 40 and had no viable virus growth in the laboratory by hospital day 41, suggesting no risk of infectivity, despite positive RT-PCR results, which prolonged his hospital stay. Notably, this case showed infectivity for at least 24 days from disease onset, which is longer than the discontinuation of transmission-based precautions recommendation by CDC. Thus, our findings suggest that the timeline for discontinuing transmission-based precautions may need to be extended for patients with prolonged illness. Additional large-scale studies are needed to draw definitive conclusions on the appropriate clinical management for these patients.

Discovery of baicalin and baicalein as novel, natural product inhibitors of SARS-CoV-2 3CL protease in vitro

Human infections with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) cause coronavirus disease 19 (COVID-19) and there is currently no cure. The 3C-like protease (3CLpro), a highly conserved protease indispensable for replication of coronaviruses, is a promising target for development of broad-spectrum antiviral drugs. To advance the speed of drug discovery and development, we investigated the inhibition of SARS-CoV-2 3CLpro by natural products derived from Chinese traditional medicines. Baicalin and baicalein were identified as the first non-covalent, non-peptidomimetic inhibitors of SARS-CoV-2 3CLpro and exhibited potent antiviral activities in a cell-based system. Remarkably, the binding mode of baicalein with SARS-CoV-2 3CLpro determined by X-ray protein crystallography is distinctly different from those of known inhibitors. Baicalein is perfectly ensconced in the core of the substrate-binding pocket by interacting with two catalytic residues, the crucial S1/S2 subsites and the oxyanion loop, acting as a "shield" in front of the catalytic dyad to prevent the peptide substrate approaching the active site. The simple chemical structure, unique mode of action, and potent antiviral activities in vitro, coupled with the favorable safety data from clinical trials, emphasize that baicalein provides a great opportunity for the development of critically needed anti-coronaviral drugs.

The choice of demand, supply, utilization and health promotion strategy of migrant popula-tion:A perspective of behavioral model of medical service utilization / 中国卫生政策研究

With the continuous expansion of the domestic population flow,the medical and health services is-sues of migrant population are becoming more and more serious. Based on the three aspects of the demand,supply, and utilization of health services,this article explores and analyzes the utilization of health services for migrant popu-lation in Beijing in 2015 on the basis of behavioral models. The results showed that the prevalence of chronic diseases and the frequency of disease in migrant population are relatively low. The migrant population has low efficiency and overall evaluation of public health services. From the point of view of convenience and diversity of services,the sup-ply of public health services needs to be further improved. In terms of the active utilization of medical and health services,the proportion of respondents who did not participate in any medical insurance still have a large proportion, while the proportion of regular physical examination was lower. In terms of passive utilization,both outpatient and in-patients service use are low. Family income and medical insurance have influenced patients'choice of medical institu-tions to some extent. The health promotion strategy is proposed from the perspective of supply side and utilization.

Blood Routine Analysis of Patients with Herpes Zoster at Early Stage,Acute Cholecystitis and Acute Myocardial Infarction / 现代检验医学杂志

Objective To evaluate the diagnostic value of these alternant indexes by compare the results of routine blood test of early herpes zoster(HZ),acute cholecystitis and acute myocardial infarction patients.Methods According to some inclu-sion and exclusion criteria,78 HZ patients,59 acute cholecystitis and 51 acute myocardial infarction patients from October 2013 to March 2017 were included.The receiver operator characteristics(ROC)were used to evaluate the diagnostic value of the blood corpuscle indexes.Results White blood cell count(WBC),blood platelet count(PLT)and neutrophilic granulo-cyte percentage(NE%)of HZ patients were lower than the acute cholecystitis and acute myocardial infarction patients(P<0.001).Lymphocyte percentage(LYM%)and monocyte percentage(MO%)were higher than the others'.The NE% index had a certain diagnostic value(AUC=0.848,95%CI:0.792~0.905).There was a highest specificity in LYM% index(spe-cificity=0.963).Conclusion There were some clinical significance of routine blood cell count results on the early HZ diag-nosis,which can reduce the missed diagnosis and misdiagnosis rate of an early diagnosis herpes zoster.

Incidence trend of nasopharyngeal carcinoma from 1987 to 2011 in Sihui County, Guangdong Province, South China: an age-period-cohort analysis / 癌症

<p><b>INTRODUCTION</b>In the past several decades, declining incidences of nasopharyngeal carcinoma (NPC) have been observed in Chinese populations in Hong Kong, Taiwan, Los Angeles, and Singapore. A previous study indicated that the incidence of NPC in Sihui County, South China remained stable until 2002, but whether age, diagnosis period, and birth cohort affect the incidence of NPC remains unknown.</p><p><b>METHODS</b>Age-standardized rates (ASRs) of NPC incidence based on the world standard population were examined in both males and females in Sihui County from 1987 to 2011. Joinpoint regression analysis was conducted to quantify the changes in incidence trends. A Poisson regression age-period-cohort model was used to assess the effects of age, diagnosis period, and birth cohort on the risk of NPC.</p><p><b>RESULTS</b>The ASRs of NPC incidence during the study period were 30.29/100,000 for males and 13.09/100,000 for females. The incidence of NPC remained stable at a non-significant average annual percent change of 0.2% for males and -1.6% for females throughout the entire period. A significantly increased estimated annual percent change of 6.8% (95% confidence interval, 0.1%-14.0%) was observed from 2003 to 2009 for males. The relative risk of NPC increased with advancing age up to 50-59 and decreased at ages >60 years. The period effect curves on NPC were nearly flat for males and females. The birth cohort effect curve for males showed an increase from the 1922 cohort to the 1957 cohort and a decrease thereafter. In females, there was an undulating increase in the relative risk from the 1922 cohort to the 1972 cohort.</p><p><b>CONCLUSIONS</b>The incidence trends for NPC remained generally stable in Sihui from 1987 to 2011, with an increase from 2003 to 2009. The relative risks of NPC increased in younger females.</p>

Secular trend analysis of lung cancer incidence in Sihui city, China between 1987 and 2011 / 癌症

<p><b>BACKGROUND</b>With industrial and econom ic development in recent decades in South China, cancer incidence may have changed due to the changing lifestyle and environment. However, the trends of lung cancer and the roles of smoking and other environmental risk factors in the development of lung cancer in rural areas of South China remain unclear. The purpose of this study was to explore the lung cancer incidence trends and the possible causes of these trends.</p><p><b>METHODS</b>Joinpoint regression analysis and the age-period-cohort (APC) model were used to analyze the lung cancer incidence trends in Sihui, Guangdong province, China between 1987 and 2011, and explore the possible causes of these trends.</p><p><b>RESULTS</b>A total of 2,397 lung cancer patients were involved in this study. A 3-fold increase in the incidence of lung cancer in both sexes was observed over the 25-year period. Joinpoint regression analysis showed that while the incidence continued to increase steadily in females during the entire period, a sharp acceleration was observed in males starting in 2005. The full APC model was selected to describe age, period, and birth cohort effects on lung cancer incidence trends in Sihui. The age cohorts in both sexes showed a continuously significant increase in the relative risk (RR) of lung cancer, with a peak in the eldest age group (80-84 years). The RR of lung cancer showed a fluctuating curve in both sexes. The birth cohorts identified an increased trend in both males and females; however, males had a plateau in the youngest cohorts who were born during 1955-1969.</p><p><b>CONCLUSIONS</b>Increasing trends of the incidence of lung cancer in Sihui were dominated by the effects of age and birth cohorts. Social aging, smoking, and environmental changes may play important roles in such trends.</p>

Estimation of cancer burden in Guangdong Province, China in 2009 / 癌症

<p><b>BACKGROUND</b>Surveying regional cancer incidence and mortality provides significant data that can assist in making health policy for local areas; however, the province- and region-based cancer burden in China is seldom reported. In this study, we estimated cancer incidence and mortality in Guangdong Province, China and presented basic information for making policies related to health resource allocation and disease control.</p><p><b>METHODS</b>A log-linear model was used to calculate the sex-, age-, and registry-specific ratios of incidence to mortality (I/M) based on cancer registry data from Guangzhou, Zhongshan, and Sihui between 2004 and 2008. The cancer incidences in 2009 were then estimated according to representative I/M ratios and the mortality records from eight death surveillance sites in Guangdong Province. The cancer incidences in each city were estimated by the corresponding sex- and age-specific incidences from cancer registries or death surveillance sites in each area. Finally, the total and region-based cancer incidences and mortalities for the entire population of Guangdong Province were summarized.</p><p><b>RESULTS</b>The estimated I/M ratios in Guangzhou (3.658), Zhongshan (2.153), and Sihui (1.527) were significantly different (P < 0.001), with an average I/M ratio of 2.446. Significant differences in the estimated I/M ratios were observed between distinct age groups and the three cancer registries. The estimated I/M ratio in females was significantly higher than that in males (2.864 vs. 2.027, P < 0.001). It was estimated that there were 163,376 new cancer cases (99,689 males and 63,687 females) in 2009; it was further estimated that 115,049 people (75,054 males and 39,995 females) died from cancer in Guangdong Province in 2009. The estimated crude and age-standardized rate of incidences (ASRI) in Guangdong Province were 231.34 and 246.87 per 100,000 males, respectively, and 156.98 and 163.57 per 100,000 females, respectively. The estimated crude and age-standardized rate of mortalities (ASRM) in Guangdong Province were 174.17 and 187.46 per 100,000 males, respectively, and 98.59 and 102.00 per 100,000 females, respectively. In comparison with the western area and the northern mountain area, higher ASRI and ASRM were recorded in the Pearl River Delta area and the eastern area in both males and females.</p><p><b>CONCLUSIONS</b>Cancer imposes a heavy disease burden, and cancer patterns are unevenly distributed throughout Guangdong Province. More health resources should be allocated to cancer control, especially in the western and northern mountain areas.</p>

Percutaneous implantation of 125I seed- strip combined with biliary stent for the treatment of malignant biliary obstruction：analysis of 38 cases / 介入放射学杂志

Objective To investigate the clinical efficacy of percutaneous transhepatic insertion of biliary stent (PTIBS) combined with radioactive seed implantation in treating malignant biliary obstruction. Methods A total of 38 patients with malignant biliary obstruction were enrolled in this study. Radioactive 125I seed was used, and each 125I seed was 4.5 mm in length and 0.8 mm in diameter. The 125I seeds were placed in a catheter to prepare the 125I seed- strip. PTCD was carried out first, then percutaneous catheterization was performed and a guide- wire was inserted through the catheter until it passed the obstructed biliary segment. The obstructed segment was dilated by a balloon - catheter, which was followed by PTIBS. An 8 - 10 F drainage - catheter was placed into the biliary duct through the stent. Finally, guided by fluoroscopy the catheter with the 125I seed- strip was inserted via the drainage- catheter to the area that was planned to be radiated. The external drainage- catheter was wrapped and fixed to the skin, or was imbedded under the skin. Results Of the 38 patients with malignant biliary obstruction, successful PTIBS combined with radioactive seed implantation was accomplished in 36 patients. After the treatment, the serum bilirubin level fell to normal or near normal range in all patients (P < 0.05). No obvious side effects were observed. Conclusion For the treatment of malignant biliary obstruction, percutaneous transhepatic insertion of biliary stent combined with radioactive 125I seed - strip implantation is a safe and effective method.

Study on the timeliness of the notifiable communicable diseases surveillance system in Fujian province, China, 2004 / 中华流行病学杂志

<p><b>OBJECTIVE</b>To understand the timeliness of the notifiable communicable diseases surveillance system in Fujian province.</p><p><b>METHODS</b>Database from the internet based communicable diseases reporting system was used.</p><p><b>RESULTS</b>The 50th percentile of time between the disease diagnosed and report recorded in medical faculties was 1 day in 2004 which was 6 days less than that in 2001 - 2003. The timeliness rate of 0 day was 46.46%, a 2.7 times over that in 2001 - 2003. The timeliness of notifiable communicable diseases surveillance system in different administrative areas, reporting units and on different diseases was significantly different. Time between the disease diagnosed and report recorded was the shortest in those cases reported by hospitals and traditional Chinese medicine(TCM) hospitals at the county level and above, with 50th percentile as 0 day, but the timeliness rate of 0 day was 50.76% with 70.04% of the cases were reported from hospitals and TCM hospitals of county level and above. Length between the disease diagnosed and reported was the longest in those cases recorded by Centers for Disease Control and Prevention(CDCs) with the 50th percentile as 3 days. The source of cases recorded by CDCs came from hospitals at the township level, where there was no connection to internet but the reporting cards had to be sent to local CDCs. Time between the disease being diagnosed and reported was 2 days in those cases reported by hospitals at the township level. 21.21% of cases were recorded by hospitals of township level and CDCs. The 50th percentile of time shown between the reported records and confirmed by CDCs was 4 hours The 24 hour timeliness rate was 63.65%.</p><p><b>CONCLUSION</b>The timeliness of the notifiable communicable diseases surveillance system had been improved significantly after the medical personnel recording the cases directly through internet. Timeliness could be further improved through access to internet at the hospitals of township level, training of staff and better hospital management systems.</p>