Case Report: Mutations in JAK3 causing severe combined immunodeficiency complicated by disseminated Bacille Calmette-Guérin disease and Pneumocystis pneumonia.

Background: As a form of severe combined immunodeficiency (SCID), Janus kinase 3 (JAK3) deficiency can be fatal during severe infections in children, especially after inoculation of live-attenuated vaccines. We report a unique case of JAK3 deficiency with two compound heterozygous JAK3 mutations complicated by disseminated Bacille Calmette-Guérin (BCG) disease and Pneumocystis pneumonia. Case description: A 5-month-old Chinese girl presented with recurring fever and productive cough after BCG vaccination and ineffective antibiotic treatment. Chest CT demonstrated bilateral infiltrations, enlarged mediastinal and axillary lymph nodes, and hypoplasia of the thymus. Mycobacterium tuberculosis and Pneumocystis jirovecii were detected from blood samples by sequencing. Acid-fast bacilli were also found from the sputum aspirate and gastric aspirate. Lymphocyte subset analyses indicated T-B+NK- immunodeficiency, and gene sequencing identified two heterozygous missense mutations (one unreported globally) in the Janus homology 7 (JH7) domain of JAK3. The patient received rifampicin, isoniazid, ethambutol, and trimethoprim/sulfamethoxazole and was discharged after improvements but against advice. Outcome: The patient died at 13 months of age due to severe infections and hepatic damage. Discussion: SCID should be recognized before inoculation of live-attenuated vaccines in children. Newborn screening for SCID is advocated. Further investigations are needed to better understand the pathogenicity of the variants and molecular mechanism of the JH7 domain of JAK3.

Patterns of mental health problems before and after easing COVID-19 restrictions: Evidence from a 105248-subject survey in general population in China.

BACKGROUND: The COVID-19 pandemic has alarming implications for individual and population level mental health. Although the future of COVID-19 is unknown at present, more countries or regions start to ease restrictions. The findings from this study have provided the empirical evidence of prevalence and patterns of mental disorders in Chinese general population before and after easing most COVID-19 restrictions, and information of the factors associated with these patterns. METHODS: A cross-sectional population-based online survey was carried out from February to March 2020 in the general population across all provinces in China. The 12-item General Health Questionnaire (GHQ-12) was incorporated in the survey. Latent class analyses were performed to investigate the patterns of mental disorders and multinomial logistic regressions were used to examine how individual and regional risk factors can predict mental disorder patterns. RESULTS: Four distinctive patterns of mental health were revealed in the general population. After the ease of most COVID-19 restrictions, the prevalence of high risk of mental disorders decreased from 25.8% to 20.9% and prevalence of being high risk of unhappiness and loss of confidence decreased from 10.1% to 8.1%. However, the prevalence of stressed, social dysfunction and unhappy were consistently high before and after easing restrictions. Several regional factors, such as case mortality rate and healthcare resources, were associated with mental health status. Of note, healthcare workers were less likely to have mental disorders, compared to other professionals and students. CONCLUSIONS: The dynamic management of mental health and psychosocial well-being is as important as that of physical health both before and after the ease of COVID-19 restrictions. Our findings may help in mental health interventions in other countries and regions while easing COVID-19 restrictions.

An ultra HPLC-MS/MS method for quantification of hypidone hydrochloride (YL-0919) and application to a pharmacokinetic study.

Aim: Hypidone hydrochloride (YL-0919) was a novel combined selective serotonin reuptake inhibitor and 5-hydroxytryptamine receptor agonist for treatment of major depressive disorder. Quantitation of YL-0919 in plasma samples was critical for evaluation of its pharmacokinetics in clinical studies. Methodology & results: An ultra HPLC-MS/MS method has been developed and validated. Plasma samples were extracted by SPE method and then chromatographed on an Acquity BEH C18 column. Detection was performed on an API-5500 tandem mass spectrometer using positive ESI. Conclusion: A sensitive and robust method was developed and validated for quantitative analysis of YL-0919 in human plasma samples for the first time. And this novel method was successfully applied to investigate pharmacokinetic profiles of YL-0919 in Chinese healthy subjects.

Risk factors of severe hand, foot and mouth disease in Shantou, China: a case-control study.

INTRODUCTION: In clinical perspectives, how to distinguish a small proportion of children at risk of developing neurological complications from a large number of children with mild symptoms still remains a challenge for primary care doctors. METHODOLOGY: From January 2012 to December 2015, 225 cases with severe hand, foot and mouth disease (HFMD) matched with 492 controls were enrolled in the age-matched, case-control study. Continuous variables were examined by univariate analysis using a chi-squared or Fisher's exact test, and categorical variables were reported by relative risks (odd's ratio). Multivariate logistic regression was used to analyze the independent risk factors for severe HFMD. RESULTS: Peak body temperature over 37.5℃，total duration of fever over 3 days, lethargy, enterovirus 71 (EV71) infection were independent risk factors for severe HFMD. CONCLUSIONS: Peak body temperature over 37.5℃，total duration of fever over 3 days, lethargy, EV71 infection were independent risk factors for severe HFMD.

Nasal carriage of common bacterial pathogens among healthy kindergarten children in Chaoshan region, southern China: a cross-sectional study.

BACKGROUND: Nasal colonization with bacterial pathogens is associated with risk of invasive respiratory tract infections, but the related information for Chinese healthy children is scarce. METHODS: This cross-sectional study was conducted with healthy children from 6 kindergartens in the Chaoshan region, southern China during 2011-2012. Nasal swabs were examined for five common bacterial pathogens: Streptococcus pneumoniae, Haemophilus influenzae, Haemophilus parainfluenzae, Moraxella catarrhalis, and Staphylococcus aureus. RESULTS: Among 1,088 children enrolled, 79.6 % (866) were target-bacterial carriers, of which 34.4 % (298/866) were positive for ≥2 bacteria species. The most common pathogen in the bacterial carriers was M. catarrhalis (76.6 %), followed by S. pneumoniae (26.6 %), S. aureus (21.8 %), H. parainfluenzae (12.7 %), and H. influenzae (2.3 %). Multiple logistic regression analyses showed negative associations between age and the overall or multiple bacterial carriage, and between the father's education level and multiple bacterial carriage (all p < 0.05). Age was negatively associated with the carriage of M. catarrhalis and S. pneumoniae, and positively associated with the S. aureus carriage (all p < 0.0001). CONCLUSIONS: This study shows high nasal carriage of common pathogenic bacteria and coexistence of multiple pathogens in healthy Chaoshan kindergarten children, with M. catarrhalis as the commonest colonizer. Increasing age of children and higher paternal education are associated with lower risk of bacterial carriage. Longitudinal follow-up studies would be helpful for better understanding the infection risk in bacterial pathogen carriers.

Viral aetiology of acute respiratory infections among children and associated meteorological factors in southern China.

BACKGROUND: Acute respiratory infections (ARIs) are common in children and mostly caused by viruses, but the significance of the detection of multiple viruses in ARIs is unclear. This study investigated 14 respiratory viruses in ARIs among children and associated meteorological factors in Shantou, southern China. METHODS: Paired nasal/throat-flocked swabs collected from 1,074 children with ARIs, who visited outpatient walk-in clinics in a tertiary hospital between December 2010 and November 2011, were examined for fourteen respiratory viruses--influenza viruses (FluA, FluB), respiratory syncytial viruses (RSV A and B), human coronaviruses (hCoV: 229E, OC43, HKU1, NL63), human metapneumoviruses (hMPV A and B), parainfluenza viruses (PIV1-4), human rhinoviruses (HRV A, B, C), enteroviruses (EV), adenoviruses (ADV), human bocavirus (hBoV), and human parechoviruses (hPeV)--by multiplex real-time PCR. RESULTS: We identified at least one virus in 82.3% (884/1,074) and multiple viruses in 38.6% (415/1,074) of patients. EV and HRV were the most frequently detected single viruses (42.3%, 374/884 and 39.9%, 353/884 respectively) and co-detected pair (23.1%, 96/415). Overlapping seasonal trends of viruses were recorded over the year, with dual peaks for EV and single peaks for the others. By logistic regression analysis, EV was positively associated with the average temperature and humidity, hCoV, and PIV4, but negatively with HRV, PIV3, and hBoV. HRV was inversely associated with EV and PIV3. CONCLUSIONS: This study reports high viral detection and co-detection rates in pediatric ARI cases mainly due to EV and HRV. Many viruses circulated throughout the year with similar seasonal trends in association with temperature, humidity, and wind velocity. Statistically significant associations were present among the viruses. Understanding the polyviral etiology and viral interactions in the cases with multiple viruses warrants further studies.

A new synthetic Cu(II) compound, [Cu3(p-3-bmb)2Cl4·(CH3OH)2]n, inhibits tumor growth in vivo and in vitro.

Copper(II) mixed-ligand complex, [Cu3(p-3-bmb)2Cl4 (CH3OH)2]n (Cu(II) compound), where p-3-bmb=1((2-(pyridine-3-yl)-1H-benzoimidazol-1-yl) methyl)-1Hbenzotriazole, has been recently found to possess potent anti-tumor activities both in vivo and in vitro. In this study, we demonstrated that Cu(II) compound significantly inhibited tumor growth in mice that inoculated with S180 cells. Meanwhile, the viabilities of HeLa and SGC-7901 cells were inhibited by Cu(II) compound with IC50 values in the range of 5-30 µM. Further mechanistic studies revealed that Cu(II) compound treatment induced cell cycle arrested at G1 phase through p53, p21, cyclinD1, cdk4, pRb and E2F1. Cu(II) compound treatment also induced apoptosis of HeLa and SGC-7901 cells which were accompanied with decrease in mitochondrial membrane potential, increase in reactive oxygen species production, release of cytochrome C, cleavage of caspase-9, caspase-3 and poly ADP-ribose polymerase (PARP) as well as activations of bcl-2 and bax. These results indicate that Cu(II) compound has a promising potential to become a novel anti-cancer agent.

Sexual behaviors and awareness of sexually transmitted infections among Chinese university students.

INTRODUCTION: This study investigated the current state of attitudes, behaviors, and knowledge concerning sex and sexually transmitted infections (STIs) among Chinese university students. METHODOLOGY: A cross-sectional anonymous university intranet-based survey was given to students attending the Shantou University, Guangdong, China using a 28-item questionnaire. RESULTS: Of 3425 website visitors, 1030 university students completed the survey, of which 80% were between 20 and 25 years of age, 76% considered pre-marital sex acceptable, 21% had had sexual intercourse, and 45% of sexually active students had engaged in oral sex, anal intercourse, or sex with strangers. Students had limited knowledge and awareness about common STIs, symptoms, and complications. Three percent of the sexually active students reported having had STIs and another 8% were not sure whether they had or not. Most students had misconceptions about transmission and prevention of STIs. The internet was the main information resource for 76% of students. CONCLUSIONS: Despite having more open attitudes and behaviors towards sex, students' STI knowledge and awareness of STI risks was considerably limited, raising concerns about a likely rise in STI incidence. Prior knowledge of STIs had no significant influence. Targeted educational measures such as online education and counseling via Chinese websites and social media, and the provision of safer sex and STI-related information by health experts to university students are suggested.

Prior knowledge, older age, and higher allowance are risk factors for self-medication with antibiotics among university students in southern China.

BACKGROUND: Self-medication with antibiotics (SMA) has been reported among university students in many countries, but little research has been done on this issue in China. The objective of this study was to evaluate knowledge and behaviors of university students and risk factors concerning SMA. METHODOLOGY/PRINCIPAL FINDINGS: Using a novel questionnaire-based data collection instrument, an anonymous online survey was conducted with the students of Shantou University (STU), a university comprising 8 schools/colleges in eastern Guangdong, China. Of 1,300 respondents (13.8% of total eligible participants), 47.8% had self-treated with antibiotics. Logistic regression analysis identified prior knowledge of antibiotics (PKA), older age, and higher monthly allowance as independent risk factors for SMA. PKA significantly influenced students' knowledge about antibiotics, their uses, and common adverse reactions (all p<0.05). Among self-medicated students, 61.7% used antibiotics at least twice in the previous year. Community pharmacies were the major source of self-prescribed antibiotics. Reported common indications for SMA were sore throat (59.7%), fever (38.2%), cough (37.4%), runny nose (29.3%), and nasal congestion (28.7%). While 74.1% of self-medication episodes were based on students' own experiences, only 31.1% of students claimed to understand the package insert. Alteration of antibiotics and dosage during the course of self-treatment was made by 63.8% and 55.6% of students, respectively. At least two kinds of antibiotics were simultaneously taken by 82.6% of students. The majority of self-medicated students failed to complete the course of antibiotics. Adverse reactions were reported by 16.3% of students. Amoxicillin was the most common antibiotic used for self-medication. CONCLUSIONS: High prevalence of SMA was noted among STU students. Presence of risk factors and risk-associated behaviors/attitudes in the study population calls for focused educational intervention and stricter governmental legislation and regulation of antibiotic use and sale in pharmacies.

[Biological characteristics of human umbilical cord-derived mesenchymal stem cells and their differentiation into neurocyte-like cells].

OBJECTIVE: To investigate the isolation and expansion of mesenchymal stem cells (MSCs) from human umbilical cord Wharton's jelly and their biological identities, and explore the possibility of inducing human umbilical cord-derived MSCs to differentiate into neurocyte-like cells. METHODS: The growth and proliferative abilities of human umbilical cord-derived MSCs were observed, and their immunophenotypes were determined by flow cytometry. Salvia miltiorrhiza and beta-sulfhydryl alcohol were adopted to induce the cells to differentiate. The differentiated and undifferentiated cells were identified with immunocytochemistry. The pleiotrophin and nestin genes were measured by RT-PCR. RESULTS: A population of human umbilical cord-derived MSCs were isolated from human umbilical Wharton's jelly; they were processed to obtain a fibroblast-like population of cells and could be maintained in vitro for extended periods with stable population doubling, and they were expanded as undifferentiated cells in culture for more than 10 passages, indicating their proliferative capacity. The human umbilical cord-derived MSCs were positive for CD(29), CD(44), CD(59), CD(105), but negative or weakly expressed the markers of hematopoietic cells such as CD(14), CD(33), CD(34), CD(28), CD(45) and CD(117). The important GVHD correlation markers were negative or weakly expressed, including CD(80) (B7-1), CD(86) (B7-2), CD(40) and CD(40L). Salvia miltiorrhiza beta-sulfhydryl alcohol could induce the MSCs to express nestin, a marker of neuronal precursor stem cells at early stage of differentiation. Later, they exhibited neural phenotypes, expressing beta-tubulin III and neurofilament (NF) and glial fibrillary acidic protein (GFAP). It was confirmed by RT-PCR that the MSCs could express pleiotrophin either before or after the induction of salvia miltiorrhiza, furthermore, after the induction the expression was markedly enhanced and the nestin gene was also expressed. CONCLUSION: The human MSCs could be isolated from human umbilical cord Wharton's jelly, and it was easy to propagate these MSCs. The negative GVHD correlated markers might result from the fact that MSCs had no HLA barrier, which may suggest potential clinical significance. The MSCs are capable of differentiating into neurocyte-like cells and they may represent an alternative stem cell source for CNS cells transplantation.

Human umbilical cord Wharton's Jelly-derived mesenchymal stem cells differentiation into nerve-like cells.

BACKGROUND: The two most basic properties of mesenchymal stem cells (MSCs) are the capacities to self-renew indefinitely and differentiate into multiple cells and tissue types. The cells from human umbilical cord Wharton's Jelly have properties of MSCs and represent a rich source of primitive cells. This study was conducted to explore the possibility of inducing human umbilical cord Wharton's Jelly-derived MSCs to differentiate into nerve-like cells. METHODS: MSCs were cultured from the Wharton's Jelly taken from human umbilical cord of babies delivered after full-term normal labor. Salvia miltiorrhiza and beta-mercaptoethanol were used to induce the human umbilical cord-derived MSCs to differentiate. The expression of neural protein markers was shown by immunocytochemistry. The induction process was monitored by phase contrast microscopy, electron microscopy (EM), and laser scanning confocal microscopy (LSCM). The pleiotrophin and nestin genes were measured by reverse transcription-polymerase chain reaction (RT-PCR). RESULTS: MSCs in the Wharton's Jelly were easily attainable and could be maintained and expanded in culture. They were positive for markers of MSCs, but negative for markers of hematopoietic cells and graft-versus-host disease (GVHD)-related cells. Treatment with Salvia miltiorrhiza caused Wharton's Jelly cells to undergo profound morphological changes. The induced MSCs developed rounded cell bodies with multiple neurite-like extensions. Eventually they developed processes that formed networks reminiscent of primary cultures of neurons. Salvia miltiorrhiza and beta-mercaptoethanol also induced MSCs to express nestin, beta-tubulinIII, neurofilament (NF) and glial fibrillary acidic protein (GFAP). It was confirmed by RT-PCR that MSCs could express pleiotrophin both before and after induction by Salvia miltiorrhiza. The expression was markedly enhanced after induction and the nestin gene was also expressed. CONCLUSIONS: MSCs could be isolated from human umbilical cord Wharton's Jelly. They were capable of differentiating into nerve-like cells using Salvia miltiorrhiza or beta-mercaptoethanol. The induced MSCs not only underwent morphologic changes, but also expressed the neuron-related genes and neuronal cell markers. They may represent an alternative source of stem cells for central nervous system cell transplantation.

Autoimmune hepatitis associated with Graves' disease.

A 31-year-old woman with Graves' disease with a 12-month-history of propylthiouracil intake and autoantibodies in the sera was admitted to our hospital. The differential diagnosis between autoimmune hepatitis and propylthiouracil-induced hepatitis was intractable. Steroid therapy was started and she showed a complete response to the treatment. Liver biopsy demonstrated acute hepatitis and plasma cell infiltration. A second liver biopsy, which was performed 10 months after starting steroid therapy, showed some inflammatory cells in the portal tracts. These findings suggest that she had been suffering from autoimmune hepatitis.