miR-351-3p promotes rat amniotic fluid-derived mesenchymal stromal cell proliferation via targeting the coding sequence of Abca4.

Amniotic fluid-derived mesenchymal stromal cells (AFMSCs) present different features, depending on the isolation timing and culture conditions. The lack of uniform experimental standards hinders the comparison of results from different studies on AFMSCs. Moreover, understanding the molecular mechanisms that underlie the features of AFMSCs isolated at different embryonic developmental stages might allow the obtention of more viable and highly proliferative AFMSCs through genetic modification. We isolated AFMSCs from pregnant rats at embryonic day (E)12, E15, E18, and E21 and compared their cell proliferation capacity and transcriptome. The cell counting kit-8 assay and RNA sequencing revealed that E12 and E15 AFMSCs showed different characteristics from E18 and E21 AFMSCs. Therefore, AFMSCs were divided into two groups: early (E12 and E15) and late (E18 and E21) pregnancy-stage groups. Next, we screened the gene/microRNA pair Abca4/miR-351-3p that was related to cell proliferation. Abca4 knockdown/overexpression suggested that this gene represses the proliferation of AFMSCs, which is a newly discovered function of this gene. Finally, dual luciferase reporter gene assays confirmed that miR-351-3p targeted the coding sequence of Abca4 and regulated AFMSC proliferation. miR-351-3p promotes AFMSC proliferation via targeting the coding sequence of Abca4. Our findings provide a molecular foundation for further research for obtaining AFMSCs with a higher proliferation capacity.

Complete genome sequencing and evolutionary analysis of hepatitis C virus subtype 6a, including strains from Guangdong Province, China.

We performed an evolutionary analysis using whole genome sequence isolates of hepatitis C virus (HCV) 6a from Guangdong Province and reference sequences from various countries. Less than 5% of the HCV genome was found to be under positive selection. The E1 and E2 proteins had the highest proportion of positively selected sites both within and outside of CD8 T cell epitopes in all of the strains. Regions corresponding to CD8 T cell epitopes were under negative selection except in the isolates from Guangdong. Furthermore, we found evidence of three introductions of the virus into Guangdong from Vietnam and other Southeast Asian countries. Thus, this study provides information about the transmission of HCV 6a by comparison of full-length sequences, indicating the impact of selective constraints in Guangdong and across China.

Low prevalence of antibodies against SARS-CoV-2 among voluntary blood donors in Guangzhou, China.

Since the first case of COVID-19 reported in late December of 2019 in Wuhan, China, the SARS-CoV-2 virus has caused approximately 20 million infections and 732 thousand deaths around the world by 11 August 2020. Although the pathogen generally infects the respiratory system, whether it is present in the bloodstream and whether it poses a threat to the blood supply during the period of the outbreak is of serious public concern. In this study, we used enzyme-linked immunosorbent assay (ELISA) to screen total antibodies against SARS-CoV-2 in 2199 blood donors, who had donated blood at the Guangzhou Blood Center during the epidemic. The Ig-reactive samples were further characterized for IgA, IgG, and IgM subtypes by ELISA and viral nucleic acid by real-time polymerase chain reaction. Among the 2199 plasma samples, seven were reactive under total antibodies' screening. Further testing revealed that none of them had detectable viral nucleic acid or IgM antibody, but two samples contained IgA and IgG. The IgG antibody titers of both positive samples were 1:16 and 1:4, respectively. Our results indicated a low prevalence of past SARS-CoV-2 infection in our blood donors, as none of the tests were positive for viral nucleic acid and only 2 out of 2199 (0.09%) of samples were positive for IgG and IgA. There would be a limited necessity for the implementation of such testing in blood screening in a COVID-19 low-risk area.

The miR-532-3p/Chrdl1 axis regulates the proliferation and migration of amniotic fluid-derived mesenchymal stromal cells.

BACKGROUND: Amniotic fluid-derived mesenchymal stromal cells (AFMSCs) are promising stem cells for regeneration medicine. However, AFMSCs isolated at different stages of pregnancy have different biological characteristics, and the therapeutic effects can differ in vivo and in vitro. The mechanisms underlying these differences have not been defined. METHODS: Bioinformatics analysis of the AFMSC transcriptome identified Chrdl1 as one of the differentially expressed genes. We evaluated the effects of Chrdl1 overexpression or knockdown on the proliferation and migration of AFMSCs. Target prediction was performed using miRanda software to identify the upstream microRNA of Chrdl1. The interaction between Chrdl1 mRNA and its upstream microRNA was evaluated using a dual-luciferase reporter gene assay. RESULTS: Chrdl1 was expressed at lower levels in AFMSCs derived from the early stages of pregnancy. It could suppress AFMSC proliferation and migration. miR-532-3p promoted AFMSC proliferation and migration by targeting the 3' UTR of Chrdl1 and downregulating its expression.

Novel hepatitis B virus surface antigen mutations associated with occult genotype B hepatitis B virus infection affect HBsAg detection.

The causative factors of occult hepatitis B infection are complicated and not yet been fully elucidated. Mutations in hepatitis B virus (HBV) S gene are one of the factors may contributing to occult infection. In this study, 89 blood donors with genotype B occult HBV infection were investigated. Fifty-seven hepatitis B surface antigen (HBsAg)-positive/HBV DNA-positive blood donors served as control group for comparison. Occult HBV-related mutations with a high incidence (P < .05) in the S gene were identified. To further verify these occult infection-related mutations, a conservative full-gene expression vector of HBV B genotype (pHBV1.3B) was constructed. Then, the mutant plasmids on the basis of pHBV1.3B were constructed and transfected into HepG2 cells. Extracellular as well as intracellular HBsAg was analysed by electrochemical luminescence and cellular immunohistochemistry. Ten occult infection-related mutations (E2G, Q101R, K122R, M133T, D144E, G145R, V168A, S174N, L175S and I226S) were significantly more frequent in the occult infection group (P < .05). Five of the ten mutations (E2G, D144E, G145R, V168A and S174N) strongly decreased extracellular HBsAg level (P < .05) in the transfection system. Notably, the E2G mutation had the most significant impact on the ratio of extracellular HBsAg (3.8% vs pHBV1.3B) and intracellular HBsAg (239.3% vs pHBV1.3B) (P < .05), and the fluorescence density of E2G mutant HBsAg was significantly higher than that of pHBV1.3B (P < .0001). Hence, ten mutations were associated with genotype B occult HBV infection; E2G and V168A were novel mutations which we confirmed significantly affect HBsAg detection. E2G might cause HBsAg secretion impairment that results in intracellular accumulation and a decrease in HBsAg secretion.

HCV genotype 6 prevalence, spontaneous clearance and diversity among elderly members of the Li ethnic minority in Baisha County, China.

The epidemiology of hepatitis C virus varies widely across geographical regions and ethnic groups. Our previous study showed that 6 strains isolated from Baisha County, Hainan Island, China, were all new genotype 6 (gt6) subtypes which differed significantly from subtypes of other regions. In the current study, we conducted a comprehensive epidemiological survey of HCV in the Li ethnic group, native to Baisha County. Anti-HCV antibodies were detected by 2 independent ELISAs in all participants, and positive results confirmed by the recombinant immunoblot assay (RIBA) and HCV RNA viral loads were measured. Univariate chi-square test and multivariable logistic regression analyses were used to determine the risk factors for HCV infection and spontaneous clearance rates. Indeterminate RIBA results were excluded or included in analyses; consequently, findings were expressed as a range. Direct sequencing of partial regions within NS5B and E1 was employed for genotyping. Among 1682 participants, 117 to 153 were anti-HCV positive (7.0%-9.1%), with 42.7%-52.6% confirmed to have cleared infection. Anti-HCV positivity was associated with older age (≥60 years) (OR = 0.02, 95% CI 0.01-0.05, P < 0.01) and surgery (OR = 2.75, 95% CI 1.36-5.57, P < 0.01), with no significant difference found between the HCV infection group and the HCV spontaneous clearance group. The gt6 subtype distribution characteristics of Baisha County were unique, complex and diverse. The sequences did not cluster with known gt6 subtypes but formed 4 Baisha community-specific groups. HCV infection in members of the Li minority ethnic group is characterized by high prevalence rates in the elderly, high spontaneous clearance rates and broad gt6 diversity.

Association of HLA-DQB1*03:01 and DRB1*11:01 with spontaneous clearance of hepatitis C virus in Chinese Li ethnicity, an ethnic group genetically distinct from Chinese Han ethnicity and infected with unique HCV subtype.

Specific human leukocyte antigen (HLA) class I and class II alleles have been associated with spontaneous clearance or persistent infection of hepatitis C virus (HCV), which seemed to be restricted by the host's ethnicity and viral genotype. Recently we reported a high prevalence and spontaneous clearance rate of HCV in a cohort of Chinese Li ethnicity who were infected with new variants of HCV genotype 6. In this study, we found that the distribution of HLA class I and class II alleles in HCV infected individuals of Chinese Li ethnicity (n = 143) was distinct from that of Chinese Han ethnicity which was reported in our previous study. HLA-DRB1*11:01 and DQB1*03:01 were more prevalent in Chinese Li subjects who cleared HCV spontaneously than those who were chronically infected (P = .036 and P = .024, respectively), which were consistent with our previous report regarding the Chinese Han population. Multivariate logistic regression analysis showed that DQB1*03:01 (odds ratio = 3.899, P = .017), but not DRB1*11:01, associated with HCV spontaneous clearance, independent of age, sex, and IFNL3 genotype. Because DQB1*03:01 and DRB1*11:01 were tightly linked because of linkage disequilibrium, our results clearly supported the associations of these two alleles with HCV spontaneous clearance in Chinese Li as well as Han ethnicity.

Characterization of monocytic and granulocytic subsets of myeloid-derived suppressor cells in blood donors with occult hepatitis B virus infection.

Myeloid-derived suppressor cells (MDSCs) accumulate from many diseases. MDSCs are rarely explored in occult hepatitis B virus infection (OBI). The frequency of monocytic MDSCs (M-MDSCs) and granulocytic MDSCs (G-MDSCs) in OBI carriers was analyzed for correlation with clinical parameters, which was no different between OBI and healthy individuals, whereas the frequency of M-MDSCs but G-MDSCs in OBI was significantly lower than that observed in chronic hepatitis B carriers (0.4% vs 0.7%, P = 0.0004). The frequency of MDSCs was not correlated with clinical parameters and viral load of OBI, suggesting that the absence of HBsAg in OBI carriers might not induce the accumulation of MDSCs.

Hepatitis C virus 3b strains in injection drug users in Guangdong Province, China, may have originated in Yunnan Province.

The distribution of hepatitis C virus (HCV) genotypes/subtypes varies among different populations. Here, we investigated HCV infection and its genotype distribution in injection drug users (IDUs) in Guangdong Province of China. A total of 318 IDUs from two prisons were recruited. The genotypes/subtypes of HCV in IDUs were determined by phylogenetic analysis using E1 and/or NS5B gene sequences. Our previous data on blood donors (BDs) with no history of drug use were used as control population data for comparison. Our results showed that the prevalence of HCV 3b (20.9% vs. 3.6%, P = 3.4E-9) and 6a (57.0% vs. 39.8%, P = 1.2E-5) was higher in IDUs than in BDs. In contrast, the prevalence of HCV 1b (43.4% vs. 5.6%, P = 9.8E-23) in BDs was higher than in IDUs. Phylogeographic analysis indicated that HCV 3b migrated from Yunnan to Guangdong Province and became endemic, with further transmission to other regions of China. The trend of HCV 3b dissemination in China in IDUs requires further attention, and a strategy for prevention and therapy is needed.

Association of killer cell immunoglobulin-like receptors with spontaneous clearance of hepatitis C virus in the Chinese population.

BACKGROUND: Natural killer (NK) cells are critical components in innate immune response to viral infection. Killer cell immunoglobulin-like receptors (KIRs) are involved in regulating the balance of activation or inhibitory function of NK cells. However, the association of KIRs with the spontaneous clearance of hepatitis C virus (HCV) remains unclear in the Chinese population. STUDY DESIGN AND METHODS: A total of 407 HCV-seropositive voluntary blood donors were recruited, including 203 with spontaneous viral clearance and 204 with chronic infection. The presence of KIR genes was detected individually by polymerase chain reaction with sequence-specific primers. Data of HLA and interleukin-28B (IL28B) genotypes were extracted from our previous study. RESULTS: Our results showed that KIR2DL2, 2DS2, 2DL2/2DL3, and 2DL5A-/2DL5B+ were more frequent in subjects with HCV clearance than those with chronic infection (odds ratio [OR], 1.640, p = 0.034; OR, 1.664, p = 0.032; OR, 1.636, p = 0.040; and OR, 2.601, p = 0.012, respectively). Multivariate logistic regression analysis showed that KIR2DL5A-/2DL5B+ associated with HCV clearance (OR, 2.448, p = 0.027), independent of sex, IL28B, and other KIRs. In contrast, KIR2DL3/2DL3 (OR, 0.610, p = 0.034) as well as 2DL3/2DL3+HLA-C1 or C1C1 (OR, 0.580, p = 0.017; and OR, 0.639, p = 0.025, respectively) was found associated with chronic HCV infection. The presence of the homozygous KIR2DL3 with or without its HLA ligand increased the OR of developing chronic HCV infection in the context of IL28B. CONCLUSIONS: In this study we identified KIR2DL5A-/2DL5B+ associated with HCV spontaneous clearance, while KIR2DL3/2DL3, 2DL3/2DL3+HLA-C1, or C1C1 associated with chronic infection. Our study highlighted the fact that the roles of KIR and KIR-HLA contributed to the control of HCV infection by innate immune responses.

An evaluation of asymptomatic Dengue infections among blood donors during the 2014 Dengue outbreak in Guangzhou, China.

In 2014, an outbreak of dengue virus (DENV) infection led to 45 171 clinical cases diagnosed in Guangdong province, Southern China. However, the potential risk of blood donors asymptomatically infected with DENV has not been evaluated . In the current study we detected anti-DENV IgG antibody and RNA in volunteer Chinese blood donors. We found that anti-DENV IgG antibody was positively detected in 3.4% (51/1500) and two donors were detected as being DENV RNA positive out of 3000 blood samples. We concluded that the presence of potential DENV in blood donors might be potential risk for blood safety. Therefore, screening for DENV infection should be considered in blood donations during a period of dengue outbreak in high epidemic area of China.

Migration patterns of hepatitis C virus in China characterized for five major subtypes based on samples from 411 volunteer blood donors from 17 provinces and municipalities.

UNLABELLED: We investigated the migration patterns of hepatitis C virus (HCV) in China. Partial E1 and/or NS5B sequences from 411 volunteer blood donors sampled in 17 provinces and municipalities located in five large regions, the north-northeast, northwest, southwest, central south, and southeast, were characterized. The sequences were classified into eight subtypes (1a, n = 3; 1b, n = 183; 2a, n = 83; 3a, n = 30; 3b, n = 44; 6a, n = 55; 6n, n = 10; 6v, n = 1) and a new subtype candidate. Bayesian evolutionary analysis by sampling trees of the E1 sequences of the five major subtypes revealed distinct migration patterns. Subtype 1b showed four groups: one is prevalent nationwide with possible origins in the north-northeast; two are locally epidemic in the central south and northwest, respectively, and have spread sporadically to other regions; and the fourth one is likely linked to the long-distance dispersion among intravenous drug users from the northwest. Subtype 2a showed two groups: the larger one was mainly restricted to the northwest and seemed to show a trend toward migration via the Silk Road; the smaller one was geographically mixed and may represent descendants of those that spread widely during the contaminated plasma campaign in the 1990s. Subtype 3a exhibited three well-separated geographic groups that may be epidemically unrelated: one showed origins in the northwest, one showed origins in the southwest, and the other showed origins in the central south. In contrast, subtype 3b had a mixture of geographic origins, suggesting migrations from the southwest to the northwest and sporadically to other regions. Structurally resembling the tree for subtype 3a, the tree for subtype 6a showed four groups that may indicate migrations from the central south to southeast, southwest, and northwest. Strikingly, no subtype 6a strain was identified in the north-northeast. IMPORTANCE: With a population of greater than 1.3 billion and a territory of >9.6 million square kilometers, China has a total of 34 provinces and municipalities. In such a vast country, the epidemic history and migration trends of HCV are thought to be unique and complex but variable among regions and are unlikely to be represented by those observed in only one or at best a few provinces and municipalities. However, due to the difficulties in recruiting patients, all previous studies for this purpose have been based only on data from limited regions, and therefore, geographical biases were unavoidable. In this study, such biases were greatly reduced because we utilized samples collected from volunteer blood donors in 17 provinces and municipalities. To our knowledge, this is the first study in which the HCV isolates represented such a large portion of the country, and thus, the results should shed light on the current understanding of HCV molecular epidemiology.

HLA-B alleles B*15:01 and B*15:02: opposite association with hepatitis C virus infection in Chinese voluntary blood donors.

BACKGROUND: Although human leukocyte antigens (HLA) have been shown in association with the outcomes of hepatitis C virus (HCV) infection among different ethnic groups, such studies remain absent in China, where the HCV prevalence is higher than the global average. METHODS: In this study, 426 HCV-infected and 709 uninfected blood donors were analyzed, among whom the HLA alleles were sequenced using a high-resolution genotyping method. RESULTS: At the 2-digit level, none of the alleles showed a statistical difference between the HCV-infected and uninfected groups. However, at the 4-digit level, the HLA-B alleles B*15:01 and B*15:02 showed an opposite association with HCV infection, i.e. B*15:01 was significantly higher in the HCV-infected group (odds ratio, OR = 1.561, p = 0.010), while B*15:02 was significantly higher in the uninfected group (OR = 0.778, p = 0.016). We also identified a higher frequency of B*13:02 in the HCV-infected group (OR = 1.515, p = 0.009) and a higher frequency of B*07:05 in the uninfected group (OR = 0.299, p = 0.001). CONCLUSIONS: The frequencies of four HLA alleles, B*07:05, B*13:02, B*15:01, and B*15:02, were found to be significantly different between the HCV-infected and uninfected blood donors in China, revealing an inverse relation of B*15:01 and B*15:02 with HCV infection. This finding suggests that the ethnic genetic variations of HLA may greatly affect the host immune responses against HCV.

Increased prevalence of hepatitis C virus subtype 6a in China: a comparison between 2004-2007 and 2008-2011.

Different hepatitis C virus (HCV) genotypes exhibit differences in disease pathogenesis and progression, as well as disease outcomes and response to therapy. Tracking the change of HCV genotypes in various epidemiological settings is critical for both disease surveillance and the development of improved antiviral treatment. Here, we tracked the changes in the prevalence of the HCV genotypes in China between 2004-2007 and 2008-2011. HCV-RNA-positive sera were collected from volunteer blood donors during the period 2008-2011. The genotypes were determined by phylogenic analysis using the NS5B and E1 sequences. Geographical and demographic distribution patterns related to the HCV genotypes obtained in 2008-2011 were compared with our previous study, which recorded data in the period 2004-2007. Pearson chi-square test and t-test were used to statistically analyze the results. In 2008-2011, HCV subtypes 1b and 6a were detected in 43.8 % (184/420) and 34.3 % (144/420), respectively. The male/female ratio was found to be higher for HCV genotype 6 than for genotypes 1 and 2. When compared with the period of 2004-2007, although no significant difference was found in gender or age for genotypes 1, 2, 3 and 6, the subtype 6a frequency was significantly increased from 11 % to 26.5 % in the blood donors from outside of Guangdong Province in 2008-2011. A pattern of increase in HCV subtype 6a was found in blood donors outside of Guangdong Province, indicating that HCV subtype 6a has rapidly spread from Guangdong to other regions of China over the past 10 years.

Lower peripheral blood CD4+ lymphocyte ratio is associated with severe bronchopulmonary dysplasia.

OBJECTIVE: To elucidate the characteristics of lymphocyte subsets in bronchopulmonary dysplasia (BPD) diagnosis following Jensen's criterion to understand the spectrum of lymphocytes in different degrees of BPD. STUDY DESIGN: This single-center retrospective cohort study included 120 neonates admitted to the neonatal intensive care unit between 1 July 2014 and 30 June 2021, who had undergone peripheral blood lymphocyte subpopulation detection. RESULTS: Thirty-one neonates were included in the control group, whereas 33 infants with BPD were included in the case group. In addition, we selected 56 infants with a gestational age (GA) <37 weeks without BPD who were receiving oxygen therapy. Among the three groups, the B cell and NK cell frequencies were significantly higher and the frequencies of T cells and CD4+ cells were significantly lower in the BPD group. In newborns without BPD, the distribution of T lymphocyte subsets was similar at different GAs. Comparing different degrees of BPD, the patients in the grades 2-3 BPD group had significantly lower percentages of T lymphocytes and CD4+ T cells than those in the other groups. Remarkably, the frequencies of NK cells were significantly higher in patients with grades 2-3 BPD, and the Treg cells slightly increased with BPD severity, although the differences were not significant. CONCLUSION: Healthy neonates had similar ratios of lymphocyte subsets among different GAs; although as the GAs increased, the percentage of lymphocytes increased slightly. Severe BPD was associated with lower CD4+ T cells and higher NK cells. However, whether such changes were the cause or the consequence of BPD has not been determined.

Altered gut microbiota is associated with the formation of occult hepatitis B virus infection.

Hepatitis B virus (HBV), a common blood transmission pathogen worldwide, can lead to viral hepatitis, cirrhosis, liver cancer, and other liver diseases. In particular, occult hepatitis B virus infection (OBI) may be caused by an immune response leading to suppressed virus replication. Gut microbiota can change the immunity status of the human body and, therefore, affect the replication of HBV. Thus, to identify whether there are differences in gut microbiota between HBV carriers and OBI carriers, we collected fecal samples from 18 HBV carriers, 24 OBI blood donors, and also 20 healthy blood donors as negative control. After 16S sequencing, we found that the abundance of Faecalibacterium was significantly reduced in samples from OBI blood donors compared with those from healthy blood donors. Compared with samples from HBV carriers, the samples from OBI blood donors had a significantly increased abundance of Subdoligranulum, which might stimulate immune activation, thus inhibiting HBV replication and contributing to the formation of occult infection. Our findings revealed the potential role of gut microbiota in the formation of OBI and further provided a novel strategy for the treatment of HBV infection.IMPORTANCEOccult hepatitis B virus infection (OBI) is a special form of hepatitis B virus infection with hepatitis B surface antigen (HBsAg) positive and hepatitis B virus (HBV) DNA negative. Gut microbiota may contribute to the immune response leading to suppressed virus replication and, thus, participates in the development of OBI. The study on gut microbiota of OBI blood donors provides novel data considerably advancing our understanding of the immune mechanism for the determination of occult hepatitis B virus infection, which is helpful for improving the strategy of the treatment of HBV infection.

A reference interval study of ferritin and transferrin levels in donors from two blood centers.

Blood donors not only save the lives of patients but also play an important role in the development of medical and health services. Therefore, it is particularly important to pay attention to the blood health of blood donors who are at a high risk of iron deficiency. Detection of serum ferritin and transferrin is an important basis for the diagnosis of iron deficiency anemia. However, to the best of our knowledge, the levels of serum ferritin and transferrin, and the influencing factors, such as age and type of donation, in blood donors have not been clarified. In the present study, the serum ferritin and transferrin levels of donors from two blood centers were investigated. Demographic data were collected from the donors, and their serum ferritin and transferrin levels were tested. A total of 1,817 donors were enrolled and were eligible for evaluation. Reference intervals (RIs) for ferritin and transferrin were obtained from blood donors, and it was revealed that the ferritin and transferrin levels of blood donors were associated with age. Furthermore, serum transferrin levels were associated with the type of donation; the serum transferrin RI level was significantly higher in platelet-only donors compared with in whole blood donors. It was also demonstrated that ferritin levels were negatively associated with transferrin levels. The present study identified RIs for ferritin and transferrin levels in blood donors, and indicated that age and type of donation were important factors affecting ferritin and transferrin levels in blood donors. These findings may prove useful for blood donation recruitment and screening strategies in China, and could promote the health of blood donors.

A comparison study between Candida parapsilosis sepsis and Candida albicans sepsis in preterm infants.

In this study, we aimed to investigate the clinical characteristics of Candida parapsilosis sepsis in preterm infants. In this retrospective analysis of the clinical data of 11 cases of Candida parapsilosis sepsis and 13 cases of C. albicans sepsis, the two groups were compared for research using one-way analysis of variance (one-way ANOVA), chi2 test, and non-conditional logistic regression analysis. Compared to the C. albicans sepsis group, the C. parapsilosis group demonstrated a significantly lower birth weight (1331.8 +/- 252.41 vs. 1721.2 +/- 589.08) and significantly longer hospital stay (69.909 +/- 20.782 vs. 38.385 +/- 19.923) (t'/t = 2.160, -3.787; p = 0.045, 0.01, respectively); the incidences of retinopathy of prematurity (ROP) (72.7% vs. 30.8%), tienam administration (72.7% vs. 23.1%), pneumothorax, and thoracic closed drainage (27.3% vs. 0) were higher (chi2 = 4.196, 5.916, 4.052; p = 0.041, 0.015, 0.044, respectively). Logistic regression analysis indicated only hospital stay and tienam administration in the regression equation (chi2 = 18.008, p = 0.000). Compared with C. albicans sepsis, an average length hospital stay and administration of tienam are the high-risk factors for C. parapsilosis sepsis. With regard to the other predisposing factors of preterm infant fungal sepsis, there were no differences between the two groups.

[Clinical features of Candida albicans sepsis in preterm infants: an analysis of 13 cases].

OBJECTIVE: To investigate the clinical features of Candida albicans sepsis in preterm infants. METHODS: Retrospective analysis was performed on the clinical data of 13 preterm infants with Candida albicans sepsis, who were born at 28 to 36 weeks of gestational age and who weighed between 1400 and 2815 g. RESULTS: The infants were infected with Candida albicans at the age of 19±11 d, with the main clinical manifestations being apnea, poor response, poor skin perfusion, blood oxygen concentration decrease, dark skin, yellowish skin, heart rate increase in the rest state, copious phlegm and difficulty in weaning from the ventilator. The infants showed significantly decreased platelet and increased C-reactive protein (CRP), platelet distribution width (PDW), alanine transaminase (ALT), creatine kinase isoenzyme-MB (CK-MB), total bilirubin (TBIL), creatine kinase (CK), and lactate dehydrogenase (LDH). CK and LDH were significantly decreased after 2 weeks of antifungal therapy. Only 3 cases developed drug resistance to fluconazole and these showed response when treated with voriconazole instead. Of the 13 cases, 10 were cured, 2 abandoned therapy and 1 died. CONCLUSIONS: The clinical manifestations of Candida albicans sepsis are nonspecific in preterm infants. Infectious diseases are probably caused by Candida albicans in preterm infants 2-3 weeks after birth. Preterm infants show decreased platelet and increased CRP, PDW, ALT, CK-MB, TBIL, CK, and LDH when infected with Candida albicans.

Case Report: Identification of Two Variants of ALG13 in Families With or Without Seizure and Binocular Strabismus: Phenotypic Spectrum Analysis.

Background: Genetic causes in most affected children with intellectual disability and/or development delay remain unknown. Methods: To identify potential variants responsible for these disorders, we recruited 161 affected families and performed whole-exome sequencing and associated bioinformatics analysis. Results: In the present study, we report the identification of variants in the ALG13 gene in two of the families. In family 1, a known pathogenic missense variant (c.23T > C; p.V8A) of ALG13 was identified in a boy and his mother. In family 2, a novel missense variant (c.862C > G; p.L288V) of the same gene was identified in the affected boy and his phenotypically normal mother. Genotype-phenotype correlation analysis by comparing reported 28 different variants (HGMD) showed that three major phenotypes, including various seizures/epilepsy, intellectual disability, and development delay (such as growth, speech, motor, etc.), are present in most affected individuals. However, other phenotypes, such as strabismus and absence of seizure in our second patient, are not reported if any, which may represent a unique case of X-linked recessive nonsyndromic disorder caused by a mutation in ALG13. Conclusion: We identified two missense variants in ALG13 in a cohort of 161 families with affected individuals diagnosed as intellectual disability and/or development delay. A novel c.862C > G mutation may represent a case of X-linked recessive.