A multicenter prospective study of next-generation sequencing-based newborn screening for monogenic genetic diseases in China.

BACKGROUND: Newborn screening (NBS) is an important and successful public health program that helps improve the long-term clinical outcomes of newborns by providing early diagnosis and treatment of certain inborn diseases. The development of next-generation sequencing (NGS) technology provides new opportunities to expand current newborn screening methodologies. METHODS: We designed a a newborn genetic screening (NBGS) panel targeting 135 genes associated with 75 inborn disorders by multiplex PCR combined with NGS. With this panel, a large-scale, multicenter, prospective multidisease analysis was conducted on dried blood spot (DBS) profiles from 21,442 neonates nationwide. RESULTS: We presented the positive detection rate and carrier frequency of diseases and related variants in different regions; and 168 (0.78%) positive cases were detected. Glucose-6-Phosphate Dehydrogenase deficiency (G6PDD) and phenylketonuria (PKU) had higher prevalence rates, which were significantly different in different regions. The positive detection of G6PD variants was quite common in south China, whereas PAH variants were most commonly identified in north China. In addition, NBGS identified 3 cases with DUOX2 variants and one with SLC25A13 variants, which were normal in conventional NBS, but were confirmed later as abnormal in repeated biochemical testing after recall. Eighty percent of high-frequency gene carriers and 60% of high-frequency variant carriers had obvious regional differences. On the premise that there was no significant difference in birth weight and gestational age, the biochemical indicators of SLC22A5 c.1400C > G and ACADSB c.1165A > G carriers were significantly different from those of non-carriers. CONCLUSIONS: We demonstrated that NBGS is an effective strategy to identify neonates affected with treatable diseases as a supplement to current NBS methods. Our data also showed that the prevalence of diseases has significant regional characteristics, which provides a theoretical basis for screening diseases in different regions.

Localized Instillation Enables In Vivo Screening of Targeting Peptides Using One-Bead One-Compound Technology.

The One-Bead One-Compound (OBOC) library screening is an efficient technique for identifying targeting peptides. However, due to the relatively large bead size, it is challenging for the OBOC method to be applied for in vivo screening. Herein, we report an in vivo Localized Instillation Beads library (LIB) screening method to discover targeting peptides with the OBOC technique. Inspired by localized instillation, we constructed a cavity inside of a transplanted tumor of a mouse. Then, the OBOC heptapeptide library was injected and incubated inside the tumor cavity. After an efficient elution process, the retained beads were gathered, from which three MDA-MB-231 tumor-targeting heptapeptides were discovered. It was verified that the best peptide had 1.9-fold higher tumor accumulation than the commonly used targeting peptide RGD in vivo. Finally, two targeting proteins were discovered as potential targets of our targeting peptide to the MDA-MB-231 tumor. The in vivo LIB screening method expands the scope of OBOC peptide screening applications to discover targeting peptides in vivo feasibly and reliably.

Household transmission of SARS-CoV-2 and risk factors for susceptibility and infectivity in Wuhan: a retrospective observational study.

BACKGROUND: Wuhan was the first epicentre of COVID-19 in the world, accounting for 80% of cases in China during the first wave. We aimed to assess household transmissibility of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and risk factors associated with infectivity and susceptibility to infection in Wuhan. METHODS: This retrospective cohort study included the households of all laboratory-confirmed or clinically confirmed COVID-19 cases and laboratory-confirmed asymptomatic SARS-CoV-2 infections identified by the Wuhan Center for Disease Control and Prevention between Dec 2, 2019, and April 18, 2020. We defined households as groups of family members and close relatives who did not necessarily live at the same address and considered households that shared common contacts as epidemiologically linked. We used a statistical transmission model to estimate household secondary attack rates and to quantify risk factors associated with infectivity and susceptibility to infection, accounting for individual-level exposure history. We assessed how intervention policies affected the household reproductive number, defined as the mean number of household contacts a case can infect. FINDINGS: 27 101 households with 29 578 primary cases and 57 581 household contacts were identified. The secondary attack rate estimated with the transmission model was 15·6% (95% CI 15·2-16·0), assuming a mean incubation period of 5 days and a maximum infectious period of 22 days. Individuals aged 60 years or older were at a higher risk of infection with SARS-CoV-2 than all other age groups. Infants aged 0-1 years were significantly more likely to be infected than children aged 2-5 years (odds ratio [OR] 2·20, 95% CI 1·40-3·44) and children aged 6-12 years (1·53, 1·01-2·34). Given the same exposure time, children and adolescents younger than 20 years of age were more likely to infect others than were adults aged 60 years or older (1·58, 1·28-1·95). Asymptomatic individuals were much less likely to infect others than were symptomatic cases (0·21, 0·14-0·31). Symptomatic cases were more likely to infect others before symptom onset than after (1·42, 1·30-1·55). After mass isolation of cases, quarantine of household contacts, and restriction of movement policies were implemented, household reproductive numbers declined by 52% among primary cases (from 0·25 [95% CI 0·24-0·26] to 0·12 [0·10-0·13]) and by 63% among secondary cases (from 0·17 [0·16-0·18] to 0·063 [0·057-0·070]). INTERPRETATION: Within households, children and adolescents were less susceptible to SARS-CoV-2 infection but were more infectious than older individuals. Presymptomatic cases were more infectious and individuals with asymptomatic infection less infectious than symptomatic cases. These findings have implications for devising interventions for blocking household transmission of SARS-CoV-2, such as timely vaccination of eligible children once resources become available. FUNDING: National Natural Science Foundation of China, Fundamental Research Funds for the Central Universities, US National Institutes of Health, and US National Science Foundation.

[Psychological factors of adopting and maintaining physical activity for individuals with hypertension in a community].

OBJECTIVE: To examine the impact of psychosocial factors on physical activity, so as to provide guidance for the development of an effective physical activity intervention program for individuals with hypertension. METHODS: This study used a baseline data from an intervention study on regular physical activity among hypertensive individuals. A multi-stage, stratified random sampling was utilized and finally 12 communities from 6 urban districts were chosen. Questionnaires were administrated through face-to-face interviews. A total of 586 participants were recruited and finally 559 completed the interviews with the response rate as 95.4%. Descriptive statistics and Cronbach's α coefficients were used to test the reliability. General Linear Model analysis was used to analyze the relationship between stages of physical activity and psychological factors. RESULTS: Psychosocial measures on physical activity demonstrated good reliability with Cronbach α coefficient from 0.7 to 0.9. The scores for each psychological measures increased by increasing the scores of stages of physical activity. General Linear Model analysis revealed self-efficacy (ß = 0.379) while enjoyment of physical activity (ß = 0.234) was significantly correlated with physical activity (P < 0.05). The behavioral processes and family support marginally increased the physically activity (ß = 0.069 for behavioral processes and ß = 0.163 for family support, P < 0.10). CONCLUSION: Our findings were informative for the development of community-based intervention programs on physical activity among hypertensive individuals. It indicated that physical activity intervention programs should be psychosocial theory-based, especially increasing their self-confidence and enjoyment, as well as with family support, in order to adopt and maintain the physical activities.

Time trends and age-period-cohort analyses on incidence rates of nasopharyngeal carcinoma during 1993-2007 in Wuhan, China.

BACKGROUND: Declines in incidence rates of nasopharyngeal carcinoma (NPC) were observed in Hong Kong and Taiwan but not other high-risk regions in China, while evidences from low-risk regions in China are still lacking. This study aimed to examine the time trends (1993-2007) of NPC in Wuhan (a low-risk region) and assess the birth cohort and calendar period effects on the observed temporal trends. METHOD: Using data from Wuhan Cancer Registry, age-standardized annual incidence rates of NPC were calculated by the direct method using the WHO World Standard Population (2000) as the reference. Trend in incidence rates of NPC during 1993-2007 was evaluated. Age-period-cohort models were also applied to assess the effects of age, calendar time and birth cohort on the observed temporal trends. RESULTS: A total of 1685 new NPC cases (1210 males and 475 females) were diagnosed during 1993-2007 in Wuhan. The annual percentage change in incidence rates of NPC were 0.15% (95% confidence interval: -3.88% to 4.34%) for males and -1.17% (95% confidence interval: -4.85% to 2.66%) for females. No obvious cohort or period effect on the incidence rates of NPC was observed. CONCLUSION: The incidence rates of NPC remained stable during 1993-2007 in Wuhan, a low-risk region in China.

[Research on the structure equation model of tendency on drug abuse and related influencing factors in middle school students].

OBJECTIVE: To understand the relationship of tendency on drug abuse and related influencing factors for middle school students. METHODS: A total of 603 students were assessed with self-made copying style scale, consciousness to resistance of smoking, drinking and resistance ability through a questionnaire. A relationship model was set up by structure equation modeling. RESULTS: Copying style and resistance ability had significantly direct influence on tendency of drug abuse (with standardized coefficients were 0.202 and 0.092 respectively). Consciousness to resistance of smoking and drinking had significantly indirect influence on tendency of drug abuse. The goodness of fit for the structural equation model was satisfactory, with GFI, AGFI, RMSEA as 0.981, 0.972 and 0.014 respectively. CONCLUSION: It was meaningful to grasp some copying skills and resistance ability to lower the tendency of drug abuse in middle school students.

Evaluation of effectiveness of integrated intervention program in improving drug addicts' psychological health.

OBJECTIVE: To investigate the social mental state of drug addicts in a compulsive drug abuse treatment center; evaluate the effectiveness of integrated program for the prevention of abuse relapse and improvement of drug addicts' psychological health. METHODS: The study subjects were addicts from the Wuhan Compulsive Drug Abuse Treatment Center between October 2003 and June 2004, who satisfied the inclusion criteria. A non-randomized control-intervention study design was adopted. Volunteers willing to take part in intervention were put into the intervention group with their full awareness and willingness to prevent drug abuse relapse. The control group was composed of the addicts who were willing to prevent relapse and to be followed up after their discharge. RESULTS: The effectiveness of the integrated intervention program in promoting addicts' psychological health: before the intervention, the scores of Self-Rating Anxiety Scale (SAS), the positive and negative dimensionalities of Simple Coping Style Questionnaire (SCSQ) and Chinese Perceived Stress Scales (CPSS) had no significant differences between the intervention group and the control group. After the intervention, except that the SCSQ's positive dimensionality in the intervention group was significantly higher than that in the control group, other indices in the intervention group were lower. Before and after the intervention, the psychological health level in both the groups was lower than that in the normal population; there were significant differences between addicts and normal subjects in regards with all of the indices above. CONCLUSION: Drug abuse was associated closely with addicts' social mental factors. The integrated intervention program can alleviate anxiety and stress, reduce co-morbid mental disorders and effectively improve their coping style. In conclusion, the program can promote addicts' psychological health significantly.