[Analysis of risk factors of radiation-induced toxicity in limited-stage small cell lung cancer treated with hypofractionated intensity-modulated radiotherapy].

Objective: To compare the incidence of radiation-related toxicities between conventional and hypofractionated intensity-modulated radiation therapy (IMRT) for limited-stage small cell lung cancer (SCLC), and to explore the risk factors of hypofractionated radiotherapy-induced toxicities. Methods: Data were retrospectively collected from consecutive limited-stage SCLC patients treated with definitive concurrent chemoradiotherapy in Cancer Hospital of Chinese Academy of Medical Sciences from March 2016 to April 2022. The enrolled patients were divided into two groups according to radiation fractionated regimens. Common Terminology Criteria for Adverse Events (CTCAE, version 5.0) was used to evaluate the grade of radiation esophagus injuries and lung injuries. Logistic regression analyses were used to identify factors associated with radiation-related toxicities in the hypofractionated radiotherapy group. Results: Among 211 enrolled patients, 108 cases underwent conventional IMRT and 103 patients received hypofractionated IMRT. The cumulative incidences of acute esophagitis grade ≥2 [38.9% (42/108) vs 35.0% (36/103), P=0.895] and grade ≥ 3 [1.9% (2/108) vs 5.8% (6/103), P=0.132] were similar between conventional and hypofractionated IMRT group. Late esophagus injuries grade ≥2 occurred in one patient in either group. No differences in the cumulative incidence of acute pneumonitis grade ≥2[12.0% (13/108) vs 5.8% (6/103), P=0.172] and late lung injuries grade ≥2[5.6% (6/108) vs 10.7% (11/103), P=0.277] were observed. There was no grade ≥3 lung injuries occurred in either group. Using multiple regression analysis, mean esophageal dose ≥13 Gy (OR=3.33, 95% CI: 1.23-9.01, P=0.018) and the overlapping volume between planning target volume (PTV) and esophageal ≥8 cm(3)(OR=3.99, 95% CI: 1.24-12.79, P=0.020) were identified as the independent risk factors associated with acute esophagitis grade ≥2 in the hypofractionated radiotherapy group. Acute pneumonitis grade ≥2 was correlated with presence of chronic obstructive pulmonary disease (COPD, P=0.025). Late lung injuries grade ≥2 was correlated with tumor location(P=0.036). Conclusions: Hypofractionated IMRT are tolerated with manageable toxicities for limited-stage SCLC patients treated with IMRT. Mean esophageal dose and the overlapping volume between PTV and esophageal are independently predictive factors of acute esophagitis grade ≥2, and COPD and tumor location are valuable factors of lung injuries for limited-stage SCLC patients receiving hyofractionated radiotherapy. Prospective studies are needed to confirm these results.

[Molluscicidal activity of the secondary metabolites from Streptomyces nigrogriseolus XD 2-7 against Oncomelania hupensis and its preliminary mechanisms of molluscicidal actions].

OBJECTIVE: To evaluate the storage stability of metabolites from actinomycetes Streptomyces nigrogriseolus XD 2-7 and the mollcuscicidal activity against Oncomelania hupensis in the laboratory, and to preliminarily explore the mechanisms of the molluscicidal activity. METHODS: The fermentation supernatant of S. nigrogriseolus XD 2-7 was prepared and stored at -20, 4 °C and 28 °C without light for 10 d; then, the molluscicidal effect was tested against O. hupensis following immersion for 72 h. The fermentation supernatant was boiled in a 100 °C water bath for 30 min and recovered to room temperature, and then the molluscicidal effect was tested against O. hupensis following immersion for 72 h. The pH values of the fermentation supernatant were adjusted to 4.0, 6.0 and 9.0 with concentrated hydrochloric acid and sodium hydroxide, and the fermentation supernatant was stilled at room temperature for 12 h, with its pH adjusted to 7.0; then, the molluscicidal effect was tested against O. hupensis following immersion for 72 h. The fermentation product of S. nigrogriseolus XD 2-7was isolated and purified four times with macroporous resin, silica gel and octadecylsilane bonded silica gel. The final products were prepared into solutions at concentrations of 10.00, 5.00, 2.50, 1.25 mg/L and 0.63 mg/L, and the molluscicidal effect of the final productswas tested against O. hupensis following immersion for 72 h, while dechlorination water served as blank controls, and 0.10 mg/L niclosamide served as positive control. The adenosine triphosphate (ATP) and adenosine diphosphate (ADP) levels were measured in in O. hupensis soft tissues using high performance liquid chromatography (HPLC) following exposure to the final purified fermentation products of S. nigrogriseolus XD 2-7. RESULTS: After the fermentation supernatant of S. nigrogriseolus XD 2-7 was placed at -20, 4 °C and 28 °C without light for 10 d, immersion in the stock solution and solutions at 10- and 50-fold dilutions for 72 h resulted in a 100% (30/30) O. hupensis mortality. Following boiling at 100 °C for 30 min, immersion in the stock solution and solutions at 10- and 50-fold dilutions for 72 h resulted in a 100.00% (30/30) O. hupensis mortality. Following storage at pH values of 4.0 and 6.0 for 12 h, immersion in the fermentation supernatant of S. nigrogriseolus XD 2-7 for 72 h resulted in a 100.00% (30/30) O. hupensis mortality, and following storage at a pH value of 9.0 for 12 h, immersion in the fermentation supernatant of S. nigrogriseolus XD 2-7 for 72 h resulted in a 33.33% (10/30) O. hupensis mortality (χ2 = 30.000, P < 0.05). The minimum concentration of the final purified fermentation products of S. nigrogriseolus XD 2-7 was 1.25 mg/L for achieving a 100% (30/30) O. hupensis mortality. The ATP level was significantly lower in O. hupensis soft tissues exposed to 0.10 mg/L and 1.00 mg/L of the final purified fermentation products of S. nigrogriseolus XD 2-7 than in controls (F = 7.274, P < 0.05), while no significant difference was detected in the ADP level between the treatment group and controls (F = 2.485, P > 0.05). CONCLUSIONS: The active mollcuscicidal ingredients of the S. nigrogriseolus XD 2-7 metabolites are maintained stably at -20, 4 °C and 28 °C for 10 d, and are heat and acid resistant but not alkali resistant. The metabolites from S. nigrogriseolus XD 2-7 may cause energy metabolism disorders in O. hupensis, leading to O. hupensis death.

[Activity of aromatic pyrrole-based compounds against of Schistosoma japonicum cercariae and acute toxicity to fish].

OBJECTIVE: To test the activity of aromatic pyrrole-based compounds against cercariae of Schistosoma japonicum and test their acute toxicity to fish. METHODS: A series of aromatic pyrrole-based compounds were synthesized using 4-benzyl-5-(trifluoromethyl)-1H-pyrrole-3-nitrile as the lead compound. The synthesized compounds were prepared into solutions at concentrations of 10.00, 1.00, 0.10, 0.01 mg/L, and the activity of these solutions against S. japonicum cercariae was tested in 30 min, while 0.10 mg/L and 0.01 mg/L niclosamide solutions served as a positive control and dechlorinated water with 1% dimethyl sulfoxide (DMSO) was used as a negative control, with 10 to 30 cercariae of S. japonicum in each group. In addition, the compounds were prepared into solutions at concentrations of 0.50, 0.25, 0.12, 0.06, 0.03 mg/L, and their toxicity to zebrafish was tested in 72 h, while 0.15 mg/L and 0.30 mg/L niclosamide solutions served as a positive control and dechlorinated water with 1% DMSO was used as a negative control, with 10 zebrafishes in each group. RESULTS: A total of 7 aromatic pyrrole-based compounds were successfully synthesized. Treatment with compounds 102, 104 and 106 at a concentration of 0.01 mg/L for 30 min killed all S. japonicum cercariae, and compounds 105 and 107 showed no activity against cercariae. No death of cercariae was found in the blank control group, while treatment with 0.10 mg/L niclosamide for 10 min caused a 100% mortality rate of S. japonicum cercariae and 0.01 mg/L niclosamide failed to kill S. japonicum cercariae. No zebrafish death was found 72 h post-treatment with compounds 101, 104 and 105 at a concentration of 0.03 mg/L, and exposure to compounds 102, 103 and 106 at a concentration of 0.03 mg/L for 12 h resulted in a 100% mortality rate of zebrafish. No zebrafish death occurred 72 h post-treatment with 0.50 mg/L Compound 104, and no zebrafish death was found in the blank control group, while treatment with 0.30 mg/L niclosamide for 24 h resulted in a 100% mortality rate of zebrafish. CONCLUSIONS: Compound 104 achieves a 100% mortality rate against S. japonicum cercariae at a concentration of 0.01 mg/L for 30 min, and causes no death of zebrafish at a concentration of 0.50 mg/L for 72 h, which may serve as a cercaricide candidate.

[Effects of praziquantel isomers on the proliferation and activation of the LX-2 human hepatic stellate cell line].

OBJECTIVE: To compare the effects of levo-praziquantel (L-PZQ) and dextro-praziquantel (D-PZQ) on the proliferation and activation of the human hepatic stellate cell line LX-2 in vitro. METHODS: LX-2 cells were stimulated with transforming growth factor-ß (TGF-ß). LX-2 cell proliferation was measured using the CCK-8 assay after 24 h stimulation with 0 to 50 µg/mL concentrations of praziquantel, and the gene and protein expression of type Ⅰ collagen (collagen Ⅰ), type Ⅲ collagen (collagen Ⅲ) and α-smooth muscle actin (α-SMA) was quantified in LX-2 cells using quantitative real-time PCR (qPCR) and Western blotting assays 24 h and 48 h following stimulation with 15 µg/mL praziquantel to detect LX-2 cell activation. RESULTS: There were significant differences in the survival rate of LX-2 cells between L-PZQ and D-PZQ treatments at all concentrations (F = 6.119 and 79.180, both P values < 0.05). Either L-PZQ or D-PZQ at a concentration of < 30 µg/mL showed no remarkableeffectsonthe LX-2 cell proliferation (both P values > 0.05), and L-PZQ at a concentration of > 50 µg/mL and D-PZQ at a concentration of > 40 µg/mL inhibited the LX-2 cell proliferation (both P values < 0.05), while D-PZQ at concentrations of 40 µg/mL and 50 µg/mL showed greater inhibition on LX-2 cell proliferation than L-PZQ (t = 3.419 and 8.776, both P values < 0.05). There were significant differences in the collagen Ⅰ, collagen Ⅲ and α-SMA expression in LX-2 cells at both transcriptional (F = 21.55, 79.99 and 46.70, all P values < 0.05) and translational levels (F = 20.12, 30.29 and 32.93, all P values < 0.05) among the blank control group, TGF-ß stimulation group, L-PZQ treatment group and D-PZQ treatment group. L-PZQ treatment resulted in remarkable inhibition on collagen Ⅲ and α-SMA gene expression in LX-2 cells (both P values < 0.05); however, the treatment showed no remarkable inhibition collagen Ⅰ gene expression or collagen Ⅰ, collagen Ⅲ or α-SMA protein expression in LX-2 cells (all P values > 0.05). In addition, D-PZQ treatment resulted in significant inhibition on collagen Ⅰ, collagen Ⅲ and α-SMA expression in LX-2 cells at both translational and transcriptional levels (all P values < 0.05), and D-PZQ showed higher inhibition on collagen Ⅰ, collagen Ⅲ and α-SMA gene expression in LX-2 cells than L-PZQ (all P values < 0.05). CONCLUSIONS: Both L-PZQ and D-PZQ inhibit the proliferation and activation of LX-2 cells, and D-PZQ shows a higher inhibitory activity than L-PZQ.

[Studies on resistance of Schistosoma to praziquantel XVIII Sensitivity to praziquantel in filial generations of praziquantel-resistant and -sensitive Schistosoma japonicum mixed infections].

OBJECTIVE: To investigate the sensitivity of adult worms of filial generations from praziquantel-resistant and -sensitive Schistosoma japonicum mixed infections to praziquantel. METHODS: Mice were infected with the cercariae of an experimentally generated praziquantel-resistant S. japonicum isolate [median effective dose (ED50) = 277.4 mg/kg] and a laboratory-maintained praziquantel-sensitive S. japonicum isolate (ED50 = 99.6 mg/kg) at a mixture ratio of 1:1 and 2:1, which was maintained in the laboratory via the mouse-snail cycle for 8 generations. Then, mice were infected with the cercariae of the 8th filial-generation parasite, and grouped 35 days post-infection. Mice in the 5 treatment groups were given praziquantel treatment by gavage at a single oral dose of 37.5, 75, 150, 300 mg/kg and 600 mg/kg, while animals in the control group was administered orally with 2.5% cremophor EL. All mice were sacrificed 14 days post-treatment and adult worms were collected by perfusion of the portal vein. The worm burden reductions and praziquantel ED50 values were calculated. The praziquantel-resistant S. japonicum isolate generated from experimental induction with 12 rounds of praziquantel treatment with sub-curative doses was maintained in the laboratory via the mouse-snail cycle, and mice were infected with the cercariae of the 8th filial-generation parasite. The praziquantel ED50 value against the 8th filial-generation adults was measured. RESULTS: After mice were infected with the mixture of cercariae of PZQ-resistant and -sensitive S. japonicum isolates at a ratio of 1:1, the praziquantel ED50 was 135.2 mg/kg against the adults of the 8th filial-generation parasite. After mice were infected with the mixture of cercariae of PZQ-resistant and -sensitive S. japonicum isolates at a ratio of 2:1, the praziquantel ED50 was 129.2 mg/kg against the adults of the 8th filial-generation parasite. In addition, the praziquantel ED50 was 208.4 mg/kg against the adults of the 8th filial-generation S. japonicum without the selection pressure of praziquantel. CONCLUSIONS: Compared with the experimentally induced praziquantel-resistant S. japonicum isolate, the adult worms of the filial-generation S. japonicum show a reduced sensitivity to praziquantel in the same host following infection with the mixture of cercariae of praziquantel-resistant and -sensitive S. japonicum isolates. The adult worms of the filial generation of the praziquantel-resistant S. japonicum isolate without the selection pressure of praziquantel may still maintain the resistance to praziquantel.

[Progress of researches on the actions of praziquantel against hepatic fibrosis].

Praziquantel not only has broad-spectrum anti-trematode and anti-tapeworm effects, but also has pharmacological effects such as regulating inflammatory response and anti-fibrosis. Hereby, the anti-fibrosis effect of praziquantel and its mechanism were reviewed in order to provide theoretical basis for the treatment of liver fibrosis.

[Study on the factors affecting the degradation of niclosamide in the soil].

OBJECTIVE: To investigate the factors affecting the degradation of niclosamide in the soil, so as to provide the evidence for the assessment of the environmental safety in the field snail control with niclosamide. METHODS: A high performance liquid chromatography was established for the determination of niclosamide in the field. Then, the degradation of niclosamide was investigated in soils with different moistures (10%, 30%, 50%, 70% and 90%), temperatures [(15 ± 1), (25 ± 1), (35 ± 1) °C], initial concentrations (1, 5, 10 mg/kg) and in sterilized and non-sterilized soils. In addition, the degradation of niclosamide was fitted with the first-order kinetics equation, and the degradation half-life was calculated. RESULTS: The niclosamide residues gradually decreased over time in soils with different moistures, and a higher rate of degradation was seen in soils with a higher moisture. The degradation half-life of niclosamide reduced from 4.258 d in the soil with a 10% moisture to 2.412 d in the soil with a 90% moisture. The niclosamide residues gradually decreased over time in soils with different temperatures, and a higher rate of degradation was seen in soils with a higher temperature. The degradation half-life of niclosamide reduced from 4.398 d in the soil with a temperature of (15 ± 1) °C to 2.828 d in the soil with a temperature of (35 ± 1) °C. The degradation half-lives of niclosamide were 3.212, 3.333 d and 3.448 d in soils containing niclosamide at initial concentrations of 1, 5 mg/kg and 10 mg/kg, and > 30 d and 3.273 d in sterilized and non-sterilized soils. Multiple linear regression analysis revealed that soil microorganisms (P = 0.010), moisture (P = 0.000) and temperature (P = 0.002) affected the half-life of niclosamide degradation. CONCLUSIONS: The degradation of niclosamide in soils fits the first-order kinetics equation, and presence of microorganisms, a high temperature and high moisture may accelerate the degradation of niclosamide in the soil.

Peritoneal dialysis effectively removes toxic substances and improves liver functions of liver failure patients.

OBJECTIVE: Liver failure (LF) is a clinically complex disorder that characterizes with hepatic dysfunction. This study aimed at observing the therapeutic effects of peritoneal dialysis on liver function in LF patients. PATIENTS AND METHODS: This study involves 62 patients diagnosed as LF hospitalized from February 2005 to December 2016. The 62 LF patients were randomly divided into 3 groups, including artificial liver applying plasma exchange group (PE, n = 28), peritoneal dialysis group (PD, n = 22), and conservative treatment group (CT, n=12). Laboratory indexes, including serum total bilirubin (TBiL), alanine aminotransferase (ALT), albumin (ALB), blood ammonia (AMMO), international normalized ratio (INR), and creatinine (Cr) were evaluated. Inflammatory cytokines, including tumor necrosis factor α (TNF-α), interleukin-6 (IL-6), and procalcitonin (PCT) were examined using enzyme-linked immunosorbent assay (ELISA) kit. RESULTS: Peritoneal dialysis significantly improves clinical outcomes, including decreased mortality, increased survival rate and total effective rate, compared to conservative treatment (p < 0.05). Peritoneal dialysis reduced hospitalization expenses compared to PE method and conservative treatment (p < 0.05). Peritoneal dialysis significantly removed toxic substances (including TBiL, AMMO, Cr) compared to conservative treatment (p < 0.05). The post-treatment level of Cr in peritoneal dialysis group was significantly lower compared to post-treatment level of Cr in PE group (p < 0.05). Peritoneal dialysis significantly improved liver function compared to conservative treatment (p < 0.05). Peritoneal dialysis prevented bleeding tendency compared to conservative treatment (p < 0.05). Peritoneal dialysis alleviated inflammatory response compared to conservative treatment (p < 0.05). CONCLUSIONS: Peritoneal dialysis effectively removed toxic substances and improved liver functions of liver failure patients and with a lower therapeutic cost.

[Study on the recent application of ear correction model in children with congenital auricular deformity].

Objective:To study the short-term effect of Earwell ear correction model on congenital auricular deformity in children. Method:Selected 38 children with ear malformation, a total of 42 ears, born at the age of 7 days to 176 days, and the average age was 62.40 days, and all of patients were used the U.S. Earwell correction model for correction. Result:Final auricular morphologic results were classified as excellent (normal shape), good (nearnormal shape), and poor (slight or no improvement). And the patients were divided into group 1 (neonatal period), group 2 (28-90 days) and group 3 (more than 90 days) according to age, after using the Earwell ear correction device, the result which evaluated excellent are 100.00%, 89.47% and 72.73% respectively, and the average correction times are 16.75 days, 26.26 days and 38.91 days respectively, the ratio of complications are 0, 73.68% and 100.00% respectively. Conclusion:The effection of Earwell ear correction model is significant for the correction of children with congenital auricular deformity , the earlier treatment cause the better result, the shorter of the correcting time , and the lower of the complication rate.

Biology and Control of Snail Intermediate Host of Schistosoma japonicum in The People's Republic of China.

Schistosomiasis caused by Schistosoma japonicum is a severe parasitic disease in The People's Republic of China and imposed considerable burden on human and domestic animal health and socioeconomic development. The significant achievement in schistosomiasis control has been made in last 60years. Oncomelania hupensis as the only intermediate host of S. japonicum plays a key role in disease transmission. The habitat complexity of the snails challenges to effective control. In this review we share the experiences in control and research of O. hupensis.

Association between SNPs in genes involved in folate metabolism and preterm birth risk.

We investigated the association between 12 single nucleotide polymorphisms (SNPs) in 11 genes involved in folate metabolic and preterm birth. A subset of SNPs selected from 11 genes/loci involved in the folic acid metabolism pathway were subjected to SNaPshot analysis in a case-control study. Twelve SNPs (CBS-C699T, DHFR-c594+59del19, GST01-C428T, MTHFD-G1958A, MTHFR-C677T, MTHFR-A1298C, MTR-A2756G, MTRR-A66G, NFE2L2-ins1+C11108T, RFC1-G80A, TCN2-C776G, and TYMS-1494del6) in 503 DNA samples were simultaneously tested, and included 315 preterm births and 188 controls. None of the 12 SNP genotype distributions related to the folic acid metabolism pathway showed a significant difference between preterm and term babies. The frequency of the compound mutation genotype of MTHFD-G1958A, MTR-A2756G and RFC1-G80A in preterm babies was 7.3%, which was significantly higher than the 2.7% in term babies. Seven babies carried the compound mutation genotype of MTHFD-G1958A, MTR-A2756G, and CBS-C699T, but this was not observed in term babies. The frequency of the combined wild-type genotype of MTHFD-G1958A, MTR-A2756G, MTRR-A66G, MTHFR-A1298C, NFE2L2-ins1+C11108T, and RFC1- G80A in preterm babies was 3.17%, which was significantly lower than the 7.4% in term babies. The 12 SNPs screened in this study were not independent risk factors of preterm birth. Compound mutation genotypes, including MTHFD-G1958A, MTR-A2756G, and RFC1- G80A and MTHFD-G1958A, MTR-A2756G, and CBS-C699T, may increase the risk of preterm birth. The combined wild-type genotype MTHFD-G1958A, MTR-A2756G, MTRR-A66G, MTHFR-A1298C, NFE2L2-ins1+C11108T, and RFC1-G80A may decrease the risk of preterm birth.

Diffusion-weighted MRI in early assessment of tumour response to radiotherapy in high-risk prostate cancer.

OBJECTIVE: The objective of this study was to assess the efficacy of diffusion-weighted MRI (DWI) in monitoring response to radiotherapy in high-risk prostate cancer (PC). METHODS: This retrospective study included 78 patients with high-risk PC undergoing 3.0-T MRI (supplemented by DWI) before and after intensity-modulated radiotherapy (IMRT). Based on follow-up clinical examinations, patients were divided into two groups: the recurrence group (patients who suffered biochemical/clinical recurrence within 3 years, n = 13) and the non-recurrence group (patients who were recurrence free for over 3 years, n = 65). The apparent diffusion coefficient (ADC) values before and after IMRT were compared between these two groups. The receiver-operating characteristics (ROC) analysis was carried out to investigate the discriminatory capability for pre- and post-IMRT ADC values. RESULTS: The overall ADC values were 1.04 ± 0.18 × 10(-3) mm(2) s(-1) for PCs before IMRT and 1.45 ± 0.15 × 10(-3) mm(2) s(-1) after IMRT (p < 0.001). A statistically significant difference in post-IMRT ADC values was noted between patients with and without recurrence (1.27 ± 0.14 × 10(-3) mm(2) s(-1) vs 1.49 ± 0.12 × 10(-3)mm(2) s(-1); p < 0.001), although there was no statistical difference between them in pre-IMRT ADC values (1.00 ± 0.17 × 10(-3) mm(2) s(-1) vs 1.05 ± 0.18 × 10(-3) mm(2) s(-1); p = 0.31). The ROC curve analysis revealed that the post-IMRT ADC values could help identify patients suffering recurrences (area under the curve, 0.88; p < 0.001). CONCLUSION: Marked increase in ADC values was observed in PC after radiotherapy, especially in good responders. DWI is a valuable tool for monitoring the response to radiotherapy. ADVANCES IN KNOWLEDGE: This study examined the relationship between ADC changes and tumour response to treatment of PC.

Susceptibility to praziquantel of male and female cercariae of praziquantel-resistant and susceptible isolates of Schistosoma mansoni.

Praziquantel (PZQ) is now widely used for the treatment of human schistosomiasis. However, in recent years, there has been a growing concern about the resistance of Schistosoma to PZQ. The mechanisms of PZQ action against Schistosoma and resistance of Schistosoma to PZQ are poorly understood. Here, we report differential susceptibilities to PZQ between male and female cercariae in the PZQ-susceptible and PZQ-resistant isolates of Schistosoma mansoni, using tail loss as a measurement of PZQ action. The miracidia were collected by hatching eggs collected from faeces of infected mice. Single-sex cercaria lines were made by infecting a single Biomphalaria glabrata snail with a single miracidium. The sex of each single-sex cercaria line was identified by a direct W1-specific polymerase chain reaction (PCR) technique. Single-sex cercariae of two isolates were exposed to four different concentrations of PZQ, respectively. The tail shedding of cercariae was observed under a dissecting microscope for five time points up to 100 min after adding PZQ. The results showed that male cercariae have higher tail-shedding rates than that of female cercariae when PZQ-susceptible isolates of S. mansoni are exposed to the same concentration of PZQ. But this phenomenon was not observed in the PZQ-resistant isolates. This sexual differential resistance phenomenon of S. mansoni suggests that resistance to PZQ is induced by decreasing the PZQ susceptibility of male worms. The experiment described here may also be useful for developing tests to detect PZQ resistance in the field.

Impact of the South-to-North Water Diversion Project on the transmission of Schistosoma japonicum in China.

The South-to-North Water Diversion Project (SNWDP) is currently the key, national, water-conservation project in China, designed to optimise the use of water resources and relieve the water shortages in the north of the country. As one of the main water intakes for the project, that of the Eastern Route Scheme (ERS), is a breeding site for Oncomelania hupensis (the intermediate host of Schistosoma japonicum), there is concern that the snail may be carried far to the north, in the water passing through the project. To see if they could survive and breed to the north of their current range in China, O. hupensis were collected in marshland near Nanjing City and transferred to cages, on the banks of fish ponds, in the cities of Zhenjiang (in Jiangsu province, at 32 degrees 10'N), Xuzhou (in the same province but at a latitude of 34 degrees 23'N) and Jining (in Shandong province, at 35 degrees 23'N). Except over the first 6 months in Xuzhou, the snails moved north of their natural distribution did not survive and reproduce as well as those in Zhenjiang, and all those transferred to Jining died out within 1 year. Although the snail populations in Xuzhou survived for 7-8 years and retained their infectivity to S. japonicum, histological and histochemical studies revealed abnormalities in the reproductive organs of these snails. It is concluded that, unless global warming significantly increases the minimum winter temperatures in northern China, the SNWDP is unlikely to result in the northward spread of schistosomiasis japonica.

Adult worm tegumental damage and egg-granulomas in praziquantel-resistant and -susceptible Schistosoma mansoni treated in vivo.

The effect of treatment with praziquantel (PZQ) on the tegument of adult Schistosoma mansoni worms and on liver egg-granulomas has been examined in mice infected with PZQ-resistant and -susceptible parasite isolates. Two PZQ-resistant S. mansoni isolates, one selected by passage in the laboratory under drug pressure and one from Senegal established from eggs excreted by an uncured patient, were compared with PZQ-susceptible control isolates. Scanning electron microscopic observations on the tegument of Schistosoma adult worms treated in vivo with PZQ showed that more severe damage was inflicted by PZQ on susceptible worms than on drug-resistant worms. Observations on the pathology of Schistosoma egg-granulomas in the liver of infected mice after treatment with PZQ indicated that eggs from susceptible control isolates were more sensitive to PZQ than those from drug-resistant isolates.

Susceptibility of Schistosoma japonicum to praziquantel in China.

To look for possible evidence of the development of resistance in Schistosoma japonicum to praziquantel, we conducted a field study in China. During the non-transmission period of schistosomiasis a random sample of 2860 individuals from six villages in three provinces of China were examined using a parasitological stool examination. Of the 372 stool-positive subjects, 363 subjects were treated with a single oral dose of 40 mg/kg of praziquantel. Six to Seven weeks after treatment, of 334 subjects examined using the same stool examination, stool-negative results were found in 319 patients which represents a 95.5% parasitologic cure rate. Fifteen subjects still excreting eggs were treated a second time with the same dose of praziquantel. All stool samples, including those from participants re-treated with praziquantel, were re-examined 12 weeks after the first treatment and no stool-positive subjects were found. The results indicate that there was no evidence for reduced susceptibility of S. japonicum to praziquantel despite its extensive use in the main endemic areas of China for more than 10 years. The in vitro responses to praziquantel of cercariae, miracidia and eggs of S. japonicum compared with S. mansoni demonstrate that the cercariae, miracidia and eggs of S. japonicum are more sensitive to praziquantel than those of S. mansoni. More sensitive worms would be less likely to develop resistance and this could explain why no evidence for resistance was found in S. japonicum in China.

[Construction of a genetic map and location of quantitative trait loci for yield component traits in maize by SSR markers].

Using 230 F2:3 lines derived from the hybrid of ND3138, a SSR genetic linkage map of maize (Zea mays L.) was constructed on which 80 markers distribute among 10 linkage groups and spanning maize genome about 2033.4 cM with average distance between markers being 25.42 cM. The 230 F2:3 lines were grown in a random design of one-row plot with three replication, and evaluated for ear length, bared tip, ear diameter, row number, kernel number row-1, one thousand grains weight, ear weight and grain weight plant-1. With interval mapping procedure, 30 QTLs were revealed for all traits, which distributed on 9 of 10 chromosomes of maize except chromosome 6 and accounted for from 9.5% to 55.3% of the total phenotypic variation. Genetic effects and gene action were also determined.

[Molecular identification and mapping of a maize gene (Rf3) in S-type CMS using AFLP, RFLP and SCAR techniques].

The maize CMS-S near isogenic line (NIL) developed by author and the backcross progeny (BC1) derived from it were used to identify molecular markers linked to the Rf3 gene and subsequently determine its chromosomal location on the linkage map of maize. Bulk segreant analysis was performed using AFLP technique. From the survey of AFLP primer combination, two AFLP markers, (EcoRI-AGG/MseI-CAC and EcoRI-AAC/MseI-CAG), which were named RR6 and RR7 respectively, linked to the Rf3 gene were identified. However, AFLP marker RR6 showed polymorphism between parents, and bulks were used to survey the available 100 individuals of the BC1 population, 2 out of 100 shed recombination. The recombination-rate was 2%. The genetic distance between Rf3 gene and AFLP marker RR6, was approximately 2.0 cM. And then, the RR6 was successfully cloned and sequenced, primer synthesized and converted to SCAR marker so that PCR marker can be developed for the marker-assisted selection. In RFLP analysis, marker RR6 linked to Rf3 was found to be located between RFLP loci asg20 and php20581b, and mapped on chromosome 2L.