[Immune characteristics of Plasmodium reinfections in mice following chloroquine cure of primary Plasmodium infections].

OBJECTIVE: To investigate the disease progression and immunoprotective characteristics in mice re-infected with homogeneous/heterogeneous Plasmodium strains following cure of Plasmodium infections with chloroquine at the peak of parasitemia. METHODS: C57BL/6 mice were infected with the non-lethal P. yoelii 17XNL strain, and half of mice were given treatment with chloroquine at the peak of parasitemia (9 days post-infection), while the other mice were self-cured naturally. Then, all cured mice were re-infected with the equivalent lethal P. yoelii 17XL or P. berghei ANKA strain 90 days following primary Plasmodium infections. The parasitemia levels during primary infections and reinfections were measured by microscopic examinations of Giemsa-stained thin blood films, and the levels of the IgG antibody in sera and the percentages of memory T cell subsets in spleen cells were detected in mice using ELISA and flow cytometry before and after parasite reinfections, respectively. RESULTS: Following primary infections with the P. yoelii 17XNL strain, the serum IgG antibody levels were (5.047 ± 0.924) pg/mL in the selfcured mice and (4.429 ± 0.624) pg/mL in the chloroquine-treated mice, respectively (t = 0.437, P > 0.05), which were both significantly higher than that in the uninfected mice (1.624 pg/mL ± 0.280 pg/mL) (F = 22.522, P < 0.01). There was no significant difference in the serum IgG antibody level among self-cured and chloroquine-treated mice re-infected with the P. yoelii 17XL strain or the P. berghei ANKA strain (F = 0.542, P > 0.05); however, the serum IgG antibody levels were all significantly higher in selfcured and chloroquine-treated mice re-infected with the P. yoelii 17XLstrain[(15.487±1.173)pg/mLand(15.965±1.150)pg/mL] or the P. berghei ANKA strain [(14.644 ± 1.523) pg/mL and (15.185 ± 1.333) pg/mL] relative to primary infections (F = 67.383, P < 0.01). There was no significant difference in the proportion of CD4+ [(34.208 ± 2.106), (32.820 ± 1.930), (34.023 ± 2.289), (35.608 ± 1.779) pg/mL] or CD8+ T memory cells [(17.935 ± 2.092), (18.918 ± 2.823), (17.103 ± 1.627), (17.873 ± 1.425) pg/mL] in self-cured and chloroquine-treated mice with primary infections with the P. yoelii 17XNL strain followed by re-infections with the P. yoelii 17XL strain or the P. berghei ANKA strain (F = 0.944 and 0.390, both P > 0.05); however, the proportions of the CD4+ or CD8+ T memory cells were significantly greater in self-cured and chloroquine-treated mice with primary infections with the P. yoelii 17XNL strain followed by re-infections with the P. yoelii 17XL strain or the P. berghei ANKA strain than in mice with primary infections (F = 50.532 and 21.751, both P < 0.01). CONCLUSIONS: The cure of murine Plasmodium infections with chloroquine does not affect the production of effective immune protections in mice during parasite re-infections. Following a primary infection, mice show a protection against re-infections with either homogeneous or heterogeneous Plasmodium strains, and a higher-level resistance to re-infections with homogeneous parasite strains is found than with heterogeneous strains.

[Effectiveness and safety of holmium laser therapy via flexible bronchoscopy in 40 children with tracheobronchial tuberculosis].

Objective: To explore the effectiveness and safety of holmium laser treatment via flexible bronchoscopy in children with tracheobronchial tuberculosis (TBTB). Methods: The clinical data of 40 children with TBTB admitted in Qilu Children's Hospital of Shandong University from February 2016 to June 2019 were retrospectively analyzed. According to the treatment approach, they were divided into conventional treatment group (20 cases) and holmium laser treatment group (20 cases). The sex, age, course of disease and lesion location before treatment, and the time till relief of atelectasis and airway obstruction after treatment were compared between the two groups with t test and χ2 test. Results: Among the 40 cases, 24 were males and 16 females, and 35 had lymph node fistula (87.5%) and 5 had granulation proliferation (12.5%). There was no statistically significamt difference between the conventional group and laser group in sex (male ratio: 50%（10/20） vs. 75%（15/20）, χ2=2.66, P=0.10), age （(3.2±2.2） years vs. （2.2±1.8） years, t=1.41, P=0.16), course of disease (<1 month ratio: 30%（6/20） vs. 35%（7/20）, χ2=0.11, P=0.73), lesion location (single lesion ratio： 45%（9/20） vs. 60%(12/20), χ2=0.90, P=0.34). The effectiveness was evaluated after 3 months, and the total effective rate were 100% in laser group and 40% in conventional group, the difference was significant (χ²=25.34, P<0.01). No serious adverse events occurred in the two groups during the observational period. Conclusions: Holmium laser treatment via bronchoscopy is an effective way to remove the tuberculosis foci in the trachea, which can reduce the incidence of further related complications, and could be applied in clinical approach.

[Effects of calcium supplementation during the pregnancy and early infancy stage on the body mass index and gut microbiota in the infants].

Objective: To investigate the effects of calcium supplementation during the pregnancy and early infancy stage on body mass index (BMI) and gut microbiota in the infants. Methods: A total of 1 752 healthy pregnant women and their infants (breast feeding) in two maternal and child health care hospitals of Beijing were chosen as the subjects in this study from May to October 2016. Questionnaires were used to obtain the general information and supplementation of calcium and vitamin D in mothers and their infants. The body length and weight of infants at birth and 6 months were recorded to calculate the BMI. The random number table method was used to randomly select 40 infants from each group for gut microbiota analysis (If less than 40 infants were all included in this study, 23 infants in the pregnancy and early infancy would be all treated with calcium supplements. There were 6 infants who was not added calcium during the pregnancy but added in the early infancy). Then it was compared that the effects of calcium supplementation during the pregnancy and early infancy on the BMI and gut microbiota composition of infants were determined at birth and 6 months. Results: Compared to the group with no calcium supplementation during the pregnancy ((12.76±1.23), (17.68±0.76)kg/m(2)), the BMI of infants at birth and 6 months in the group with calcium supplementation during the pregnancy ((13.51±0.47), (17.91±0.23)kg/m(2)) were significantly higher(P<0.05). In the group with maternal calcium supplementation, the BMI at 6 months ((18.63±0.52)kg/m(2)), BMI increment ((5.71±0.54)kg/m(2)) and the content of lactobacillus (21.04%±3.68%) in the only calcium supplementation subgroup in the early infancy were higher than those in only vitamin D supplementation subgroup ((17.69±0.89) kg/m(2), (4.17±1.01) kg/m(2) and 12.28%±3.86%) (P<0.05). In the group without maternal calcium supplementation, the content of lactobacillus (20.15%±4.87%) in the only calcium supplementation subgroup were also higher than those in only vitamin D supplementation subgroup (14.64%±3.71%) (P<0.05). Conclusion: Appropriate calcium supplementation during the pregnancy is good for the growth and development of the fetus. Calcium supplementation in the early infancy could increase the BMI of infants, and promote the growth of intestinal lactobacillus.

[Effect of docosahexenoic acid supplementation on infant's growth and body mass index during maternal pregnancy].

Objective: To investigate the effects of docosahexenoic acid (DHA) supplementation on infant's growth and BMI during pregnancy. Methods: A total of 1 516 healthy pregnant women delivered their babies in two maternal and child health care hospitals in Beijing and were chosen as the subjects in this cohort study from May to October 2015. Self-developed questionnaires were used to gather general information of the subjects, including age, height, weight, weight gain during pregnancy, delivery mode, DHA supplementation etc., before giving birth. Information on body length, weight, head circumference and BMI at birth and 6 months postnatal, of the infants were recorded. Breast milk was collected to test the fatty acid profiles by using the gas chromatography (GC) method at one to three months postnatally. Results: The overall rate of DHA supplementation was 47.76% among the pregnant women, in which introduction of DHA from the early and second stage of the pregnancy accounted for 49.31% and 39.64% respectively. When DHA supplementation began from the early pregnant stage, the DHA concentration showed an increase in the milk (P<0.05), whereas the supplementation began from the second and third stages did not affect the milk DHA concentration (P>0.05). Higher height and lower BMI were seen in the infants at birth and 6 months in the supplementation group when comparing to the non-supplementary group (P<0.05), with the greatest effects noticed in the earliest supplementation group. Specifically, the head circumference appeared larger from the early pregnant stage in the DHA supplementary group, than that in the non-supplement group (P=0.001). The increment of head circumference was larger than that in the other groups when the infants were 6-month old (P<0.01). Results from the partial regression analysis showed that during pregnancy, there were positive correlations between DHA supplementation and height (r=0.324, r=0.216), head circumference (r=0.221, r=0.302) as well as the increment of head circumference (r=0.276) at birth and 6 months (P<0.05). Whereas, a negative correlation was shown between DHA and the infants' BMI (r=-0.310, r=-0.371) (P<0.05) when supplementation was given during maternal pregnancy. Conclusions: When DHA supplementation program was carried out during maternal pregnancy, it could increase the height and head circumference and inhibit the rapid increase of BMI in the infants BMI. Our findings seemed helpful in promoting brain development and preventing the childhood obesity.

[The effect of paraquat on autophagy in human embryonic neural progenitor cells].

OBJECTIVE: To explore the effect of paraquat (PQ) on autophagy in human embryonic neural progenitor cells. METHODS: Using ReNcell CX cell model. After treatment with various concentration (0.00, 1.00, 10.00 and 100.00 µmol/L) of PQ, CCK8 assay was used to detect the cell viability, the transmission electron microscope was used to observe the the cell ultrastructure, the real-time polymerase chain reaction (RT-PCR) was adopted to detect mRNA expression of autophagy related genes which including LC3, Atg12, Atg5, beclin1, Atg7 and mTOR and apoptosis related genes Bax and Bcl-2. RESULTS: The cell viability was significantly inhibited after administered with 100.00 µmol/L of PQ (P<0.01). The mRNA expression of Beclin1 was significantly up-regulated and the emergency of autophagosome were observed at the concentration of 1.00 µmol/L group, while mild cell apoptosis, significantly up-regulated Atg5, Atg8, Atg7 and Atg12 mRNA expression as well as down-regulated expression of mTOR and Bax were detected at the 10.00 µmol/L of PQ group, howere, the obvious apoptosis and the up-regulated mRNA expression of mTOR and Bax were observed at the 100.00 µmol/L of PQ group, the mRNA expression of Bcl-2 were all down-regulated after administered with 1.00, 10.00 and 100.00 µmol/L of PQ and reached the lowest level at the concentration of 10.00 µmol/L. CONCLUSION: PQ can induced autophagy at the low concentration in ReNcell CX cell and autophagy might serve as a protective mechanism to ameliorate PQ-induced cytotoxic effects but apoptosis will be induced at the 100 µmol/L concentration.

MTHFR C677T variant reduces risk of sporadic Parkinson's disease in ethnic Chinese.

BACKGROUND: Genetic variability of methylenetetrahydrofolate reductase (MTHFR) may be associated with Parkinson's disease (PD). Its role in ethnic Chinese population is still unclear. Our study aimed to investigate whether MTHFR C677T variation was linked to PD risk in a Han Chinese population from mainland China. METHODS: To investigate the association with the risk of PD, we analyzed the single-nucleotide polymorphism C677T in MTHFR gene using a case-control methodology. A total of 1482 subjects included 765 patients with idiopathic PD, and 717 age- and sex-matched controls were recruited in this study. RESULTS: The T allele of MTHFR C677T was associated with a decreased risk of PD (OR = 0.80, 95% CI: 0.688-0.926, P = 0.003). Patients with CT + TT genotypes have a decreased risk of PD compared with those with CC genotypes (OR = 0.66, 95%CI: 0.532-0.813, P = 0.000). CT + TT subjects cannot be differentiated from CC subjects based on their clinical features. CONCLUSION: We showed that the C677T polymorphism in MTHFR gene was associated with decreased PD susceptibility in a Han Chinese population from mainland China. Efforts to fully elucidate the pathophysiologic role of the variant in PD should be necessary.

MCCC1/LAMP3 reduces risk of sporadic Parkinson's disease in Han Chinese.

BACKGROUND: A recent large-scale replication and heterogeneity study reported the new described GWAS locus (MCCC1/LAMP3 rs11711441) was associated with a reduced risk of Parkinson disease (PD) in Asian and Caucasian populations. Its role is still unknown in a Han Chinese population from mainland China. We genotyped the rs11711441 variant to investigate the association with risk of PD. METHODS: Using a case-control methodology, a total of 1428 Han Chinese study subjects were genotyped. We also conducted further stratified analysis according to age at onset and compared the clinical characteristics of GA + AA subjects with GG subjects. RESULTS: In this study, we confirmed that the A allele of MCCC1/LAMP3 (rs11711441) polymorphism reduces the risk to develop sporadic PD (P = 0.043). Additionally, subjects with GA + AA genotypes have a reduced risk compared to those with GG genotype (P = 0.022). The association was seen among the older age group (P = 0.014), but was not significant among the younger age group (P = 0.641). No significant differences were observed in gender, age at onset, and onset symptoms between GA + AA subjects and GG subjects. CONCLUSION: Our study, the first from Mainland China demonstrates that MCCC1/LAMP3 (rs11711441) is associated with a lower risk of PD. Further studies in additional Chinese populations and other cohorts will be useful.

Association between GBA L444P mutation and sporadic Parkinson's disease from Mainland China.

Mutations in GBA gene have been reported to be in patients with Parkinson's disease (PD) from different ethnic populations, including Taiwanese Chinese. To explore whether mutation in GBA is also associated with PD in Mainland China, we have now a case control study. The occurrence of the GBA L444P mutation was analyzed in an independent cohort of PD patients and controls from Mainland China. This mutation was present in 20/616 (3.2%) of PD compared with 1/411 (0.2%) of controls (odds ratio, OR=13.76, 95% Confidence interval, CI: 1.84-102.92, p=0.001). All carriers harbored the heterozygous genotype. In a subset analysis, the frequency of this mutation was higher both in early onset (EOPD) and late onset PD (LOPD) than in controls. However, no difference in clinical characteristics, such as gender, age at onset, onset symptoms, Hoehn-Yahr stage and UPDRS, was found between L444P carriers and non-carriers. In addition, we also explored the potential relationship between GBA L444P mutation and LRRK2 G2385R and R1628P variants in patients with PD. But no association was found, either. In conclusion, our data suggest that the GBA L444P mutation plays an important role in the development of PD also in Han-Chinese patients from Mainland China.

Research progress of triptolide-loaded nanoparticles delivery systems.

Triptolide is one of the major active components of traditional Chinese Medicine (TCM) - Tripterygium wilfordii Hook. f. (TWHf), which has been reported to be effective in the treatment of patients with a variety of inflammatory and autoimmune diseases, especially rheumatoid arthritis. However, its clinical use is restricted due to its scarce water solubility and some toxic effects. In order to find innovative ways for administering triptolide and alleviating its disadvantages, the novel types of delivery systems have been developed. This paper reviews the studies of triptolide- loaded nano drug delivery systems (NDDS) in our group during the past three years. The preparation, characterization, pharmacology and toxicity of triptolide-loaded solid lipid nanoparticles, microemulsions and polymeric nanoparticles were investigated. The results indicated that the NDDS presented more powerful activity and a lower toxicity in comparison with common drug carrier.