A biosynthetic gene cluster for the bioactive fungal sesterterpenoids variecolin ( 1) and variecolactone ( 2) was identified in Aspergillus aculeatus ATCC 16872. Heterologous production of 1 and 2 was achieved in Aspergillus oryzae by expressing the sesterterpene synthase VrcA and the cytochrome P450 VrcB. Intriguingly, the replacement of VrcB with homologous P450s from other fungal terpenoid pathways yielded three new variecolin analogues ( 5- 7). Analysis of the compounds' anticancer activity in vitro and in vivo revealed that although 5 and 1 had comparable activities, 5 was associated with significantly reduced toxic side effects in cancer-bearing mice, indicating its potentially broader therapeutic window. Our study describes the first tests of variecolin and its analogues in animals and demonstrates the utility of synthetic biology for creating molecules with improved biological activities.

Female ; Humans ; Ovarian Neoplasms/surgery* ; Sex Cord-Gonadal Stromal Tumors/surgery* ; Myxoma/surgery*

Objective: To compare the volumetric changes of cervical disc herniation (CDH) after cervical microendoscopic laminoplasty(CMEL),expansive open-door laminoplasty (EOLP) and conservative treatment. Methods: A retrospective study was conducted involving 101 patients with cervical spondylotic myelopathy(CSM),at the Department of Orthopaedic Surgery,the First Affiliated Hospital of Zhengzhou University from April 2012 to April 2021. The patients included 52 males and 49 females with an age of (54.7±11.8) years(range:25 to 86 years). Among them, 35 patients accepted CMEL treatment,33 patients accepted EOLP treatment,while 33 patients accepted conservative treatment. Volume data of CDH were measured by three-dimensional analysis of the initial and follow-up MRI images. The absorption rate and reprotrusion rate of CDH were calculated. The happening of resorption or reprotrusion was defined when the ratio was greater than 5%. The clinical outcomes and quality of life were evaluated by the Japanese Orthopaedic Association (JOA) score and the neck disability index (NDI).Quantitative data was analyzed by one-way ANOVA with post LSD-t test (multiple comparison) or Kruskal-Wallis test. Categorical data was analyzed by χ² test. Results: The follow-up time of the CMEL group,EOLP group and the conservative treatment group were (27.6±18.8)months,(21.6±6.9)months and(24.9±16.3)months respectively with no significant difference(P>0.05). Changes of CDH volume in patients:(1) There were 96 CDH of 35 patients in the CMEL group,among which 78 showed absorption. The absorption frequency was 81.3%(78/96) and the absorption rate was ranged 5.9% to 90.9%;9 CDH showed reprotrusion,the reprotrusion frequency was 9.4% (9/96) and the reprotrusion rate was 5.9% to 13.3%;(2) There were 94 CDH of 33 patients in the EOLP group,of which 45 showed absorption. The absorption prevalence was 47.9% (45/94) and the absorption rate was 5.0% to 26.7%;20 CDH showed reprotruded,with the reprotrusion frequency of 21.3% (20/94) and the reprotrusion rate was 5.8% to 28.3%;(3) There were 102 CDH in 33 patients of the conservative group. Among them, 5 showed absorption. The absorption frequency was 4.9% (5/102),and the absorption rate was 7.2% to 14.3%;58 CDH showed reprotruded with the re-protrusion ratio of 56.9% (58/102) and the re-protrusion rate was 5.4% to 174.1%. The absorption ratio and reprotrusion ratio of the CMEL group were statistically different from EOLP group or the conservative group (P<0.01).The absorption ratio and reprotrusion ratio of the EOLP group was different from conservative group (all P<0.01). In terms of clinical outcomes, the excellent/good rate of the JOA score and NDI scores in the CMEL group were different from that of conservative group (all P<0.01) but not from that of the EOLP group(P>0.05). Conclusions: CMEL is an effective method for the treatment of CSM,making CDH easier to resorption compared to the EOLP or conservative treatment,thus making a better decompression effect on the nerves. This study enlightened on a new strategy for the clinical treatment of CSM.
Male ; Female ; Humans ; Adult ; Middle Aged ; Aged ; Aged, 80 and over ; Retrospective Studies ; Intervertebral Disc Displacement/surgery* ; Conservative Treatment ; Quality of Life ; Treatment Outcome ; Spondylosis/surgery* ; Cervical Vertebrae/surgery* ; Spinal Cord Diseases ; Laminoplasty/methods* ; Decompression

OBJECTIVE: To examine the impact of COVID-19 pandemic on the epidemic status of imported malaria and national malaria control program in China, so as to provide insights into post-elimination malaria surveillance. METHODS: All data pertaining to imported malaria cases were collected from Anhui Province, Hubei Province, Henan Province, Zhejiang Province and Guangxi Zhuang Autonomous Region during the period from January 1, 2018 through December 31, 2021. The number of malaria cases, species of malaria parasites, country where malaria parasite were infected, diagnosis and treatment after returning to China, and response were compared before (from January 1, 2018 to January 22, 2020) and after the COVID-19 pandemic (from January 23, 2020 to December 31, 2021). RESULTS: A total of 2 054 imported malaria cases were reported in Anhui Province, Hubei Province, Henan Province, Zhejiang Province and Guangxi Zhuang Autonomous Region during the period from January 1, 2018 to December 31, 2021, and there were 1 722 cases and 332 cases reported before and after the COVID-19 pandemic, respectively. All cases were reported within one day after definitive diagnosis. The annual mean number of reported malaria cases reduced by 79.30% in Anhui Province, Hubei Province, Henan Province, Zhejiang Province and Guangxi Zhuang Autonomous Region after the COVID-19 pandemic (171 cases) than before the pandemic (826 cases), and the number of monthly reported malaria cases significantly reduced in Anhui Province, Hubei Province, Henan Province, Zhejiang Province and Guangxi Zhuang Autonomous Region since February 2020. There was a significant difference in the constituent ratio of species of malaria parasites among the imported malaria cases in Anhui Province, Hubei Province, Henan Province, Zhejiang Province and Guangxi Zhuang Autonomous Region before and after the COVID-19 pandemic (χ² = 146.70, P < 0.05), and P. falciparum malaria was predominant before the COVID-19 pandemic (72.30%), while P. ovale malaria (44.28%) was predominant after the COVID-19 pandemic, followed by P. falciparum malaria (37.65%). There was a significant difference in the constituent ratio of country where malaria parasites were infected among imported malaria cases in Anhui Province, Hubei Province, Henan Province, Zhejiang Province and Guangxi Zhuang Autonomous Region before and after the COVID-19 pandemic (χ² = 13.83, P < 0.05), and the proportion of malaria cases that acquired Plasmodium infections in western Africa reduced after the COVID-19 pandemic that before the pandemic (44.13% vs. 37.95%; χ² = 4.34, P < 0.05), while the proportion of malaria cases that acquired Plasmodium infections in eastern Africa increased after the COVID-19 pandemic that before the pandemic (9.58% vs. 15.36%; χ² = 9.88, P = 0.02). The proportion of completing case investigation within 3 days was significantly lower after the COVID-19 pandemic than before the pandemic (96.69% vs. 98.32%; χ²= 3.87, P < 0.05), while the proportion of finishing foci investigation and response within 7 days was significantly higher after the COVID-19 pandemic than before the pandemic (100.00% vs. 98.43%; χ² = 3.95, P < 0.05). CONCLUSIONS The number of imported malaria cases remarkably reduced in Anhui Province, Hubei Province, Henan Province, Zhejiang Province and Guangxi Zhuang Autonomous Region of China during the COVID-19 pandemic, with a decreased proportion of completing case investigations within 3 days. The sensitivity of the malaria surveillance-response system requires to be improved to prevent the risk of secondary transmission of malaria due to the sharp increase in the number of imported malaria cases following the change of the COVID-19 containment policy.
Humans ; Pandemics ; China/epidemiology* ; Incidence ; COVID-19/epidemiology* ; Malaria/prevention & control* ; Malaria, Falciparum/epidemiology*

INTRODUCTION: Pregnant women are reported to be at increased risk of severe coronavirus disease 2019 (COVID-19) due to underlying immunosuppression during pregnancy. However, the clinical course of COVID-19 in pregnancy and risk of vertical and horizontal transmission remain relatively unknown. We aim to describe and evaluate outcomes in pregnant women with COVID-19 in Singapore. METHODS: Prospective observational study of 16 pregnant patients admitted for COVID-19 to 4 tertiary hospitals in Singapore. Outcomes included severe disease, pregnancy loss, and vertical and horizontal transmission. RESULTS: Of the 16 patients, 37.5%, 43.8% and 18.7% were infected in the first, second and third trimesters, respectively. Two gravidas aged ≥35 years (12.5%) developed severe pneumonia; one patient (body mass index 32.9kg/m2) required transfer to intensive care. The median duration of acute infection was 19 days; one patient remained reverse transcription polymerase chain reaction (RT-PCR) positive >11 weeks from diagnosis. There were no maternal mortalities. Five pregnancies produced term live-births while 2 spontaneous miscarriages occurred at 11 and 23 weeks. RT-PCR of breast milk and maternal and neonatal samples taken at birth were negative; placenta and cord histology showed non-specific inflammation; and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific immunoglobulins were elevated in paired maternal and umbilical cord blood (n=5). CONCLUSION The majority of COVID-19 infected pregnant women had mild disease and only 2 women with risk factors (obesity, older age) had severe infection; this represents a slightly higher incidence than observed in age-matched non-pregnant women. Among the women who delivered, there was no definitive evidence of mother-to-child transmission via breast milk or placenta.
Abortion, Spontaneous/epidemiology* ; Adult ; COVID-19/transmission* ; COVID-19 Nucleic Acid Testing ; COVID-19 Serological Testing ; Cohort Studies ; Disease Transmission, Infectious/statistics & numerical data* ; Female ; Fetal Blood/immunology* ; Humans ; Infectious Disease Transmission, Vertical/statistics & numerical data* ; Live Birth/epidemiology* ; Maternal Age ; Milk, Human/virology* ; Obesity, Maternal/epidemiology* ; Placenta/pathology* ; Pregnancy ; Pregnancy Complications, Infectious/physiopathology* ; Pregnancy Outcome/epidemiology* ; Pregnancy Trimester, First ; Pregnancy Trimester, Second ; Prospective Studies ; RNA, Viral/analysis* ; Risk Factors ; SARS-CoV-2 ; Severity of Illness Index ; Singapore/epidemiology* ; Umbilical Cord/pathology* ; Young Adult

Objective: To understand the disease progression and human leukocyte antigen (HLA) gene polymorphism of HIV-infected persons without disease progress for long term, also known as long-term non-progressors (LTNPs), in Henan province. Methods: A retrospective study was conducted in 48 LTNPs with complete detection and follow-up information during 2011-2016 in Henan. Changes of CD(4)(+)T cells counts (CD(4)) and viral load (VL) during follow-up period were discussed. Polymerase chain reaction-sequence-specific oligonucleotide probe (PCR-SSOP) was used for the analyses of HLA-A, HLA-B and HLA-DRB1 alleles between LTNPs and healthy controls. Results: From 2011 to 2016, forty-eight LTNPs showed a decrease of the quartile (P(25)-P(75)) of CD(4) from 601.00 (488.50-708.72)/μl to 494.00 (367.00-672.00)/μl, and the difference was significant (P<0.05). The increase of the quartile (P(25)-P(75)) of log(10)VL from 3.40 (2.87-3.97) to 3.48 (2.60-4.37), but the difference was not significant (P>0.05). HLA polymorphism analysis revealed that HLA-B*13:02 and HLA-B*40:06 were more common in LTNPs (P<0.05), while HLA-B*46:01 and HLA-DRB1*09:01 were more common in healthy controls (P<0.05). Conclusions: The CD(4) of LTNPs in Henan showed a downward trend year by year. HLA-B*13:02 and B*40:06 might be associated with delayed disease progression for HIV infected persons in Henan.
Adult ; Alleles ; Asian People/genetics* ; China ; Disease Progression ; Female ; HIV ; HIV Infections/virology* ; HIV-1/immunology* ; HLA-B Antigens/genetics* ; Humans ; Middle Aged ; Polymorphism, Genetic ; Retrospective Studies ; Viral Load

Objective: To identify the influencing factors that leading to nonspecific responses to indeterminate HIV antibody tests, to provide scientific evidence for the differential diagnosis of HIV infection and control strategy. Methods: A case control study was conducted. The samples of HIV antibody indeterminate in confirmed Western blot (WB) tests, but were negative in HIV nucleic acid tests, were collected as HIV antibody indeterminate group from WB results of HIV confirmatory laboratories of Fujian province in 2015-2016. The general population matched group with HIV antibody screening negative samples and WB negative matched group with WB negative samples were selected as the two compared groups by matching gender and age from HIV antibody screening in Fujian province in the same period. Blood concentrations of hepatitis B surface antigen (HBsAg), anti-hepatitis C virus (HCV) antibody, anti-treponema pallidum (TP) antibody, antinuclear antibody (ANA), anti-human T-cell leukemia virus (HTLV) antibody, and alpha-fetoprotein (AFP) were detected by using enzyme-linked immunosorbent assay (ELISA). χ(2) test and multivariate non-conditional logistic regression analysis were performed to identify the influencing factors that leading to nonspecific responses, to indeterminate HIV antibody tests. Results: A total of 13 WB band patterns were observed in 110 HIV antibody indeterminate samples, in which a single p24 band (58.18%, 64/110), a single gp160 band (17.27%, 19/110) and a single p17 band (7.27%, 8/110) were the three most common patterns. The positive rate of anti-TP antibody was significantly higher in HIV antibody indeterminate samples than general population control group and WB negative control group (10.91%, 12/110 vs. 1.77%, 4/226 and 3.64%, 4/110), compared with two control groups (χ(2)=13.627 and 4.314, P<0.05). The positive rate of AFP was significantly higher in HIV antibody indeterminate samples than general population control group (18.18%, 20/110 vs. 0.44%, 1/226, χ(2)=39.736, P<0.05), the different was not significant compared with WB negative control group (18.18%, 20/110 vs. 23.64%, 26/110, χ(2)=0.990, P>0.05) While no significant differences were found between HIV antibody indeterminate group and two control groups in terms of the positive rates of ANA, HBsAg, anti-HCV antibody or anti-HTLV antibody. Conclusions: The influencing factors that leading to nonspecific responses to indeterminate HIV antibody tests appeared complicate, and the anti-TP antibody positivity might be an influencing factor responsible for nonspecific responses to indeterminate HIV antibody tests.
Adult ; Blotting, Western/methods* ; Case-Control Studies ; China/epidemiology* ; Enzyme-Linked Immunosorbent Assay/methods* ; HIV Antibodies/isolation & purification* ; HIV Infections/epidemiology* ; HIV-1/immunology* ; Humans ; Middle Aged ; Predictive Value of Tests ; Sensitivity and Specificity

Objective: To study the relations between famine exposure and the risk of chronic diseases as diabetes mellitus, obesity, hypertension, coronary heart disease and stroke in the population of Harbin. Methods: Our data was collected from the baseline survey-the China Kadoorie Biobank project (CKB) in Harbin. Retrospective cohort study design was used. Related risks on chronic diseases including diabetes mellitus, obesity, hypertension, coronary heart disease and stroke, were compared among the famine exposed or non-exposed people, respectively by logistic analysis method. Results: After adjusted for factors as age, sex, physical activity, smoking, alcohol intake, diet, family history of diseases, it appeared that the factor 'famine exposure' had increased the risks of diseases as obesity (OR=1.204, 95%CI: 1.104-1.313, P<0.01), hypertension (OR=1.315, 95%CI: 1.210-1.429, P<0.01) and coronary heart disease (OR=1.495, 95%CI: 1.369-1.632, P<0.01). The lower the age of population being exposed to famine, the greater the risk of the development of all kinds of chronic diseases. Conclusions: Famine exposure appeared a risk factor for obesity, hypertension, and coronary heart disease. It is of great significance to ensure the life-long nutrition of the people, especially in the early and adolescent stages, to prevent obesity, hypertension, and coronary heart disease in their later lives.
Adolescent ; China/epidemiology* ; Chronic Disease/epidemiology* ; Coronary Disease/epidemiology* ; Diabetes Mellitus/epidemiology* ; Female ; Humans ; Hypertension/epidemiology* ; Obesity/epidemiology* ; Pregnancy ; Prenatal Exposure Delayed Effects/epidemiology* ; Retrospective Studies ; Socioeconomic Factors ; Starvation/epidemiology*

Objective: To investigate the second or third trimester pregnancy-related anxiety on small-for-gestational-age infants. Methods: This study was based on Ma'anshan Birth Cohort Study (MABC), with 3 040 maternal-singleton pairs finally selected for data analysis, from May 2013 to September 2014. The psychological state of pregnancy was evaluated according to a self-developed 'anxiety scale for gestation'. Small-for-gestational-age was defined as 'having birth weight below the 10(th) percentile at a particular gestational week', while large-for-gestational-age infants was defined as 'having birth weight above the 90(th) percentile'. Birth weight between the 10(th) and 90(th) percentile was classified as appropriate-for-gestational age infants. χ(2) test was used to compare the distribution of characteristics in pregnancy among three groups with different birth weights. Multivariate logistic regression models were conducted to evaluate the associations between third trimester pregnancy- related anxiety and birth weight. Results: The incidence rates of small- and large-gestational-age infants were 9.6% and 16.6%, respectively. Difference between women with only one of the second or third trimester pregnancy-related anxiety syndromes and small-for-gestational-age infants showed no statistical significance. Women with both second and third trimester pregnancy-related anxieties might increase the risk of small-for-gestational-age infants (OR=1.39, 95%CI: 1.04-1.87). However, there was no significant difference between pregnancy-related anxiety and large-for- gestational-age infants (OR=1.05, 95%CI: 0.81-1.35) noticed. Conclusion: Women with second and third trimester pregnancy-related anxiety appeared a risk factor for small-for-gestational-age infants.
Anxiety/psychology* ; Birth Weight ; China/epidemiology* ; Cohort Studies ; Female ; Gestational Age ; Humans ; Infant ; Infant, Newborn ; Infant, Small for Gestational Age ; Pregnancy ; Pregnancy Complications/psychology* ; Pregnancy Trimester, Third/psychology*

Objective: To analyze the relationship between medication taken during pregnancy and congenital heart disease of the newborns. Methods: A large cross-sectional survey was conducted between August and November 2013. A questionnaire survey was conducted among the childbearing aged women, selected through multistage stratified random sampling in Shaanxi from 2010 to 2013. All of the childbearing aged women under study were in pregnancy and with definite pregnancy outcomes. Multivariable Poisson regression was conducted for data analyses. Results: A total of 28 680 cases were included in this study. The proportion of medication taken at any time during pregnancy was 16.0%, and the prevalence of congenital heart disease among the newborns was 67.9/10 000. After adjustment for factors as general demographic characteristic, history of heart disease and drug allergy and the situation of disease during pregnancy of these women, results from the multivariable Poisson regression showed that, factors as taking drugs (RR=1.95, 95%CI: 1.42- 2.68), cold medicine (RR=1.68, 95%CI: 1.07-2.64), antibiotics (RR=1.90, 95%CI: 1.25-2.90), salicylates (RR=5.01, 95%CI: 1.84-13.64) and antifungal drugs (RR=10.22, 95%CI: 3.25-32.19) during pregnancy were all related to congenital heart disease, and with the history of taking cold medicine (RR=1.90, 95%CI: 1.01-3.61), antibiotics (RR=2.18, 95%CI: 1.17-4.06), salicylates (RR=6.07, 95%CI: 1.45-25.41), antifungal drugs (RR=21.01, 95%CI: 4.17-105.87) and other drugs (RR=2.31, 95%CI: 1.19-4.47) during early pregnancy. These factors were with higher risks for congenital heart disease. Conclusion: Women of childbearing age who took cold medicine, antibiotics, salicylic acid drugs, antifungal drugs and other drugs during early pregnancy would increase the risks related to congenital heart diseases.
Adult ; Cross-Sectional Studies ; Drug Therapy ; Drug-Related Side Effects and Adverse Reactions ; Female ; Heart Diseases/epidemiology* ; Humans ; Infant, Newborn ; Pregnancy ; Pregnancy Outcome ; Prevalence ; Surveys and Questionnaires