The complete mitochondrial genome of the rodent intra-arterial nematodes Angiostrongylus cantonensis and Angiostrongylus costaricensis

The two rodent intra-arterial nematodes, Angiostrongylus cantonensis and Angiostrongylus costaricensis, can cause human ill-health. The present study aimed to characterize and compare the mitochondrial (mt) genomes of these two species, and clarify their phylogenetic relationship and the position in the phylum Nematoda. The complete mt genomes of A. cantonensis and A. costaricensis are 13,497 and 13,585bp in length, respectively. Hence, they are the smallest in the class of Chromadorea characterized thus far. Like many nematode species in the class of Chromadorea, they encode 12 proteins, 22 transfer RNAs, and two ribosomal RNAs. All genes are located on the same strand. Nucleotide identity of the two mt genomes is 81.6%, ranging from 77.7% to 87.1% in individual gene pairs. Our mt genome-wide analysis identified three major gene arrangement patterns (II-1, II-2, and II-3) from 48 nematode mt genomes. Both patterns II-1 and II-2 are distinct from pattern II-3, which covers the Spirurida, supporting a closer relationship between Ascaridida and Strongylida rather than Spirurida. Thymine (T) was highly concentrated on coding strands in Chromadorea, but balanced between the two strands in Enoplea, probably due to the gene arrangement pattern. Interestingly, the gene arrangement pattern of mt genomes and phylogenetic analysis based on concatenated amino acids indicated a closer relationship between the order Ascaridida and Rhabditida rather than Spirurida as indicated in previous studies. These discrepancies call for new research, reassessing the position of the order of Ascaridida in the phylogenetic tree. Once consolidated, the findings are important for population genetic studies and target identificatio

Case report: Reoperative parathyroidectomy for large ectopic hyperplastic parathyroid in the mediastinum of a patient with recurrent secondary hyperparathyroidism

IntroductionSecondary hyperparathyroidism (SHPT) is a common complication in hemodialysis patients with chronic renal failure uremia. For severe SHPT, parathyroidectomy is effective. Owing to the variability in parathyroid anatomy, surgical parathyroidectomy can be complex and many patients experience recurrent SHPT, which may require repeated surgery. These cases pose significant challenges to surgeons.Case descriptionAn elderly woman with recurrent severe SHPT was admitted to our hospital. Preoperative methoxyisobutylisonitrile (MIBI) examination found a large ectopic parathyroid gland in the superior mediastinum, and she underwent reoperative parathyroidectomy. A large parathyroid gland in the right anterior mediastinum and another parathyroid gland in the left lingual lobe of the thymus were removed. The patient had postoperative hypocalcemia that was successfully corrected with calcium supplementation via femoral vein catheterization. During the 1-year postoperative follow-up, the patient's iPTH was well controlled and her blood calcium was within the normal range.ConclusionWe report a case of parathyroidectomy to remove multifocal ectopic hyperplastic parathyroid tissue in the mediastinum. Preoperative MIBI accurately detected the lesions. Calcium supplementation via femoral vein catheterization successfully corrected postoperative hypocalcemia. Postoperative follow-up for 1 year indicated that the surgery was successful

Predictive value of 8-year blood pressure measures in intracerebral haemorrhage risk over 5 years

Aims The relationships between long-term blood pressure (BP) measures and intracerebral haemorrhage (ICH), as well as their predictive ability on ICH, are unclear. In this study, we aim to investigate the independent associations of multiple BP measures with subsequent 5-year ICH risk, as well as the incremental value of these measures over a single-point BP measurement in ICH risk prediction. Methods and results We included 12 398 participants from the China Kadoorie Biobank (CKB) who completed three surveys every 4–5 years. The following long-term BP measures were calculated: mean, minimum, maximum, standard deviation, coefficient of variation, average real variability, and cumulative BP exposure (cumBP). Cox proportional hazard models were used to examine the associations between these measures and ICH. The potential incremental value of these measures in ICH risk prediction was assessed using Harrell’s C statistics, continuous net reclassification improvement (cNRI), and relative integrated discrimination improvement (rIDI). The hazard ratios (95% confidence intervals) of incident ICH associated with per standard deviation increase in cumulative systolic BP and cumulative diastolic BP were 1.62 (1.25–2.10) and 1.59 (1.23–2.07), respectively. When cumBP was added to the conventional 5-year ICH risk prediction model, the C-statistic change was 0.009 (−0.001, 0.019), the cNRI was 0.267 (0.070–0.464), and the rIDI was 18.2% (5.8–30.7%). Further subgroup analyses revealed a consistent increase in cNRI and rIDI in men, rural residents, and participants without diabetes. Other long-term BP measures showed no statistically significant associations with incident ICH and generally did not improve model performance. Conclusion The nearly 10-year cumBP was positively associated with an increased 5-year risk of ICH and could significantly improve risk reclassification for the ICH risk prediction model that included single-point BP measurement

Stray dogs as indicators of Toxoplasma gondii distributed in the environment: the first report across an urban-rural gradient in China

<p>Abstract</p> <p>Background</p> <p>Toxoplasmosis is an important parasitic zoonosis caused by the protozoan <it>Toxoplasma gondii </it>that is distributed world-wide and infects a variety of hosts. However, the prevalence of <it>T. gondii </it>in the environment (such as soil, water and food) is largely unknown. Due to the technical difficulty in oocyst counting directly, an alternative assay using the serologic status of <it>T. gondii </it>in free-living animals, such as stray or free-living dogs, as an indicator, can be used to evaluate environmental contamination indirectly, as they are exposed to the same risk of infection as humans and other animals.</p> <p>Results</p> <p>In the present study, 231 stray or free-living dogs across an urban-rural gradient were examined to assess the frequency of <it>T. gondii </it>in the environment. Specific antibodies to <it>T. gondii </it>were found in 93 dogs (40.3%) by enzyme-linked immunosorbent assay (ELISA), and no statistically significant differences were observed in seroprevalences of <it>T. gondii </it>between urban dogs (38.7%) and rural dogs (41%) (<it>p </it>> 0.05).</p> <p>Conclusions</p> <p>A high seroprevalence of <it>T. gondii </it>in stray or free-living dogs in the present study indicates that there would be a wide distribution and a constant infection pressure of <it>T. gondii </it>across an urban-rural gradient, and the oocysts of <it>T. gondii </it>in the environment would be an important source of infection for humans and other animals both in urban and rural areas in China.</p

A wide landscape of morbidity and mortality risk associated with marital status in 0.5 million Chinese men and women: a prospective cohort study

Background: A comprehensive depiction of long-term health impacts of marital status is lacking. Methods: Sex-stratified phenome-wide association analyses (PheWAS) of marital status (living with vs. without a spouse) were performed using baseline (2004–2008) and follow-up information (ICD10-coded events till Dec 31, 2017) from the China Kadoorie Biobank (CKB). We estimated adjusted hazard ratios (aHRs) to evaluate the associations of marital status with morbidity risks of phenome-wide significant diseases or sex-specific top-10 death causes in China documented in 2017. Additionally, the association between marital status and mortality risks among participants with major chronic diseases at baseline was assessed. Findings: During up to 11.1 years of the median follow-up period, 1,946,380 incident health events were recorded among 210,202 men and 302,521 women aged 30–79. Marital status was found to have phenome-wide significant associations with thirteen diseases among men (p < 9.92 × 10−5) and nine diseases among women (p < 9.33 × 10−5), respectively. After adjusting for all disease-specific covariates in the final model, participants living without a spouse showed increased risks of schizophrenia, schizotypal and delusional disorders (aHR [95% CI]: 2.55, [1.83–3.56] for men; 1.49, [1.13–1.97] for women) compared with their counterparts. Additional higher risks in overall mental and behavioural disorder (1.31, 1.13–1.53), cardiovascular disease (1.07, 1.04–1.10) and cancer (1.06, 1.00–1.12) were only observed among men without a spouse, whereas women living without a spouse were at lower risks of developing genitourinary diseases (0.89, 0.85–0.93) and injury & poisoning (0.93, 0.88–0.97). Among 282,810 participants with major chronic diseases at baseline, 39,166 deaths were recorded. Increased mortality risks for those without a spouse were observed in 12 of 21 diseases among male patients and one of 23 among female patients. For patients with any self-reported disease at baseline, compared with those living with a spouse, the aHRs (95% CIs) of mortality risk were 1.29 (1.24–1.34) and 1.04 (1.00–1.07) among men and women without a spouse (pinteraction<0.0001), respectively. Interpretation: Long-term associations of marital status with morbidity and mortality risks are diverse among middle-aged Chinese adults, and the adverse impacts due to living without a spouse are more profound among men. Marital status may be an influential factor for health needs. Funding: The National Natural Science Foundation of China, the Kadoorie Charitable Foundation, the National Key R&D Program of China, the Chinese Ministry of Science and Technology, and the UK Wellcome Trust

Associations of traditional cardiovascular risk factors with 15-year blood pressure change and trajectories in Chinese adults: a prospective cohort study

Objective: How traditional cardiovascular disease (CVD) risk factors are related to long-term blood pressure change (BPC) or trajectories remain unclear. We aimed to examine the independent associations of these factors with 15-year BPC and trajectories in Chinese adults. Methods: We included 15 985 participants who had attended three surveys, including 2004–2008 baseline survey, and 2013–2014 and 2020–2021 resurveys, over 15 years in the China Kadoorie Biobank (CKB). We measured systolic and diastolic blood pressure (SBP and DBP), height, weight, and waist circumference (WC). We asked about the sociodemographic characteristics and lifestyle factors, including smoking, alcohol drinking, intake of fresh vegetables, fruits, and red meat, and physical activity, using a structured questionnaire. We calculated standard deviation (SD), cumulative blood pressure (cumBP), coefficient of variation (CV), and average real variability (ARV) as long-term BPC proxies. We identified blood pressure trajectories using the latent class growth model. Results: Most baseline sociodemographic and lifestyle characteristics were associated with cumBP. After adjusting for other characteristics, the cumSBP (mmHg × year) increased by 116.9 [95% confidence interval (CI): 111.0, 122.7] for every 10 years of age. The differences of cumSBP in heavy drinkers of ≥60 g pure alcohol per day and former drinkers were 86.7 (60.7, 112.6) and 48.9 (23.1, 74.8) compared with less than weekly drinkers. The cumSBP in participants who ate red meat less than weekly was 29.4 (12.0, 46.8) higher than those who ate red meat daily. The corresponding differences of cumSBP were 127.8 (120.7, 134.9) and 70.2 (65.0, 75.3) for BMI per 5 kg/m2 and WC per 10 cm. Most of the findings of other BPC measures by baseline characteristics were similar to the cumBP, but the differences between groups were somewhat weaker. Alcohol drinking was associated with several high-risk trajectories of SBP and DBP. Both BMI and WC were independently associated with all high-risk blood pressure trajectories. Conclusions: Several traditional CVD risk factors were associated with unfavorable long-term BPC or blood pressure trajectories in Chinese adults

MTHFR and risk of stroke and heart disease in a low-folate population: a prospective study of 156 000 Chinese adults

Background The relevance of folic acid for stroke prevention in low-folate populations such as in China is uncertain. Genetic studies of the methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism, which increases plasma homocysteine (tHcy) levels, could clarify the causal relevance of elevated tHcy levels for stroke, ischaemic heart disease (IHD) and other diseases in populations without folic acid fortification. Methods In the prospective China Kadoorie Biobank, 156 253 participants were genotyped for MTHFR and 12 240 developed a stroke during the 12-year follow-up. Logistic regression was used to estimate region-specific odds ratios (ORs) for total stroke and stroke types, IHD and other diseases comparing TT genotype for MTHFR C677T (two thymine alleles at position 677 of MTHFR C677T polymorphism) vs CC (two cytosine alleles) after adjustment for age and sex, and these were combined using inverse-variance weighting. Results Overall, 21% of participants had TT genotypes, but this varied from 5% to 41% across the 10 study regions. Individuals with TT genotypes had 13% (adjusted OR 1.13, 95% CI 1.09–1.17) higher risks of any stroke [with a 2-fold stronger association with intracerebral haemorrhage (1.24, 1.17–1.32) than for ischaemic stroke (1.11, 1.07–1.15)] than the reference CC genotype. In contrast, MTHFR C677T was unrelated to risk of IHD or any other non-vascular diseases, including cancer, diabetes and chronic obstructive lung disease. Conclusions In Chinese adults, the MTHFR C677T polymorphism was associated with higher risks of stroke. The findings warrant corroboration by further trials of folic acid and implementation of mandatory folic acid fortification programmes for stroke prevention in low-folate populations

Detection and analysis of human papillomavirus (HPV) DNA in breast cancer patients by an effective method of HPV capture

Despite an increase in the number of molecular epidemiological studies conducted in recent years to evaluate the association between human papillomavirus (HPV) and the risk of breast carcinoma, these studies remain inconclusive. Here we aim to detect HPV DNA in various tissues from patients with breast carcinoma using the method of HPV capture combined with massive paralleled sequencing (MPS). To validate the confidence of our methods, 15 cervical cancer samples were tested by PCR and the new method. Results showed that there was 100% consistence between the two methods.DNA from peripheral blood, tumor tissue, adjacent lymph nodes and adjacent normal tissue were collected from seven malignant breast cancer patients, and HPV type 16(HPV16) was detected in 1/7, 1/7, 1/7and 1/7 of patients respectively. Peripheral blood, tumor tissue and adjacent normal tissue were also collected from two patients with benign breast tumor, and 1/2, 2/2 and 2/2 was detected to have HPV16 DNA respectively. MPS metrics including mapping ratio, coverage, depth and SNVs were provided to characterize HPV in samples. The average coverage was 69% and 61.2% for malignant and benign samples respectively. 126 SNVs were identified in all 9 samples. The maximum number of SNVs was located in the gene of E2 and E4 among all samples. Our study not only provided an efficient method to capture HPV DNA, but detected the SNVS, coverage, SNV type and depth. The finding has provided further clue of association between HPV16 and breast cancer

Chronic hepatitis B virus infection and risk of stroke types: a prospective cohort study of 500,000 Chinese adults

BACKGROUND: Stroke is a leading cause of mortality and permanent disability in China, with large and unexplained geographic variations in rates of different stroke types. Chronic hepatitis B virus infection is prevalent among Chinese adults and may play a role in stroke cause. METHODS: The prospective China Kadoorie Biobank included >500 000 adults aged 30 to 79 years who were recruited from 10 (5 urban and 5 rural) geographically diverse areas of China from 2004 to 2008, with determination of hepatitis B surface antigen (HBsAg) positivity at baseline. During 11 years of follow-up, a total of 59 117 incident stroke cases occurred, including 11 318 intracerebral hemorrhage (ICH), 49 971 ischemic stroke, 995 subarachnoid hemorrhage, and 3036 other/unspecified stroke. Cox regression models were used to estimate adjusted hazard ratios (HRs) for risk of stroke types associated with HBsAg positivity. In a subset of 17 833 participants, liver enzymes and lipids levels were measured and compared by HBsAg status. RESULTS: Overall, 3.0% of participants were positive for HBsAg. HBsAg positivity was associated with an increased risk of ICH (adjusted HR, 1.29 [95% CI, 1.16–1.44]), similarly for fatal (n=5982; adjusted HR, 1.36 [95% CI, 1.16–1.59]) and nonfatal (n=5336; adjusted HR, 1.23 [95% CI, 1.06–1.44]) ICH. There were no significant associations of HBsAg positivity with risks of ischemic stroke (adjusted HR, 0.97 [95% CI, 0.92–1.03]), subarachnoid hemorrhage (adjusted HR, 0.87 [95% CI, 0.57–1.33]), or other/unspecified stroke (adjusted HR, 1.12 [95% CI, 0.89–1.42]). Compared with HBsAg-negative counterparts, HBsAg-positive individuals had lower lipid and albumin levels and higher liver enzyme levels. After adjustment for liver enzymes and albumin, the association with ICH from HBsAg positivity attenuated to 1.15 (0.90–1.48), suggesting possible mediation by abnormal liver function. CONCLUSIONS: Among Chinese adults, chronic hepatitis B virus infection is associated with an increased risk of ICH but not other stroke types, which may be mediated through liver dysfunction and altered lipid metabolism

PCSK9 genetic variants and risk of vascular and non-vascular diseases in Chinese and UK populations

Aims Lowering low-density lipoprotein cholesterol (LDL-C) through PCSK9 inhibition represents a new therapeutic approach to preventing and treating cardiovascular disease (CVD). Phenome-wide analyses of PCSK9 genetic variants in large biobanks can help to identify unexpected effects of PCSK9 inhibition. Methods and results In the prospective China Kadoorie Biobank, we constructed a genetic score using three variants at the PCSK9 locus associated with directly measured LDL-C [PCSK9 genetic score (PCSK9-GS)]. Logistic regression gave estimated odds ratios (ORs) for PCSK9-GS associations with CVD and non-CVD outcomes, scaled to 1 SD lower LDL-C. PCSK9-GS was associated with lower risks of carotid plaque [n = 8340 cases; OR = 0.61 (95% confidence interval: 0.45–0.83); P = 0.0015], major occlusive vascular events [n = 15 752; 0.80 (0.67–0.95); P = 0.011], and ischaemic stroke [n = 11 467; 0.80 (0.66–0.98); P = 0.029]. However, PCSK9-GS was also associated with higher risk of hospitalization with chronic obstructive pulmonary disease [COPD: n = 6836; 1.38 (1.08–1.76); P = 0.0089] and with even higher risk of fatal exacerbations amongst individuals with pre-existing COPD [n = 730; 3.61 (1.71–7.60); P = 7.3 × 10−4]. We also replicated associations for a PCSK9 variant, reported in UK Biobank, with increased risks of acute upper respiratory tract infection (URTI) [pooled OR after meta-analysis of 1.87 (1.38–2.54); P = 5.4 × 10−5] and self-reported asthma [pooled OR of 1.17 (1.04–1.30); P = 0.0071]. There was no association of a polygenic LDL-C score with COPD hospitalization, COPD exacerbation, or URTI. Conclusion The LDL-C-lowering PCSK9 genetic variants are associated with lower risk of subclinical and clinical atherosclerotic vascular disease but higher risks of respiratory diseases. Pharmacovigilance studies may be required to monitor patients treated with therapeutic PCSK9 inhibitors for exacerbations of respiratory diseases or respiratory tract infections. Lay summary Genetic analyses of over 100 000 participants of the China Kadoorie Biobank, mimicking the effect of new drugs intended to reduce cholesterol by targeting the PCSK9 protein, have identified potential severe effects of lower PCSK9 activity in patients with existing respiratory disease. - PCSK9 genetic variants that are associated with lower cholesterol and reduced rates of cardiovascular disease are also associated with increased risk of a range of respiratory diseases, including asthma, upper respiratory tract infections, and hospitalization with chronic obstructive pulmonary disease (COPD). - These genetic variants are not associated with whether or not individuals have COPD; instead, they are specifically associated with an increase in the chance of those who already have COPD being hospitalized and even dying, suggesting that careful monitoring of such patients should be considered during development of and treatment with anti-PCSK9 medication