Characteristics of molecular markers associated with chloroquine resistance in Plasmodium vivax strains from vivax malaria cases in Yunnan Province, China.

BACKGROUND: Chloroquine (CQ) has been the preferred clinical treatment for vivax malaria in Yunnan Province since 1958, with over 300,000 patients. This study aimed to help make trend predictions regarding variations the in anti-malarial drug susceptibility of Plasmodium vivax distributed in Yunnan Province and effectively implement monitoring measures on the efficacy of anti-malarial drugs for vivax malaria. METHODS: Blood samples collected from patients with mono-P. vivax infections were employed in this study based on the principle of cluster sampling. The whole gene of P. vivax multidrug resistance 1 protein gene (pvmdr1) was amplified by nested-PCR techniques and the PCR amplification produce were sequenced by Sanger bidirectional sequencing. The mutant loci and haplotypes of coding DNA sequence (CDS) were identified by comparison with the reference sequence (NC_009915.1) of the P. vivax Sal I isolate. Parameters such as Ka/Ks ratio were calculated using MEGA 5.04 software. RESULTS: A total of 753 blood samples from patients infected with mono-P. vivax were collected, of which 624 blood samples yielded the full gene sequence (4392 bp) of the pvmdr1 gene, with 283, 140, 119, and 82 sequences from 2014, 2020, 2021 and 2022, respectively. A total of 52 single nucleotide polymorphic (SNP) loci were detected for the 624 CDSs, of which 92.3% (48/52), 34.6% (18/52), 42.3% (22/52), and 36.5% (19/52) SNPs were detected in 2014, 2020, 2021 and 2022, respectively. All of 624 CDSs were defined for a total of 105 mutant haplotypes, with CDSs of 2014, 2020, 2021, and 2022 containing 88, 15, 21, and 13 haplotypes, respectively. Of the 105 haplotypes, the threefold mutant haplotype (Hap_87) was the starting point for stepwise evolution, and the most drastic tenfold mutations were Hap_14 and Hap_78, and the fivefold, sixfold, sevenfold, and eightfold mutations. CONCLUSIONS: In the majority of vivax malaria cases in Yunnan Province, most of them were infected with strains carrying demonstrating highly mutated in pvmdr1 genes. However, the dominant mutation strains types varied from year to year, which warrants further exploration in order to confirm the correlation between with phenotypic changes in P. vivax strains and their susceptibility to anti-malarial drugs such as chloroquine.

Molecular surveillance of chloroquine resistance in Plasmodium vivax isolates from malaria cases in Yunnan Province of China using pvcrt-o gene polymorphisms.

BACKGROUND: The efficacy of chloroquine treatment for vivax malaria has been rarely evaluated due to a lack of an appropriate testing method. The objective of this study was to conduct molecular monitoring of chloroquine resistance in Plasmodium vivax strains from vivax malaria patients in Yunnan Province, focusing on the analysis of polymorphism in the P. vivax chloroquine resistance transporter protein orthologous gene (pvcrt-o). METHODS: In accordance with the principles of a cohort study, blood samples were collected from malaria cases diagnosed with a P. vivax mono-infection in Yunnan Province from 2020 to 2022. Segmental PCR was used to amplify the whole pvcrt-o gene in the blood samples and their products were subsequently sequenced. The sequencing data were arranged to obtain the full coding DNA sequence (CDS) as well as the gene's promoter region sequences. The CDSs were aligned with the reference sequence (XM_001613407.1) of the P. vivax SalI isolate to identify the mutant loci. RESULTS: From a total of 375 blood samples taken from vivax malaria cases, 272 both whole gene CDSs (1272-1275 bp) and promoter DNA sequences (707 bp) of pvcrt-o gene were obtained. Among the whole CDSs, there were 7 single nucleotide polymorphic sites in which c.7 A>G was the minor allele frequency (MAF) site with 4.4% (12/272) detection rate. The mutation detection rate showed a significant decrease from 9.8% (10/102) in 2020 to 1.1% (1/92) in 2021 and 1.3% (1/78) in 2022, indicating statistical significance (χ2 = 11.256, P < 0.05). Among the identified 12 haplotypes, the majority of which were wild type (75.7%; 206/272). These four mutant haplotypes (Hap_3, Hap_5, Hap_9, and Hap_10) were classified as "K10 insertion type" and accounted for 12.1% (33/272). The detection rate of Hap_3 increased from 1.0% (1/102) in 2020 to 13.0% (12/92) in 2021 and 14.1% (11/78) in 2022, indicating statistical significance. A total of 23.8% (65/272) of the samples exhibited 14 bp (bp) deletions in the promoter region, occurring most frequently in the wild type haplotype (Hap_1) samples at a rate of 28.6% (59/206). CONCLUSIONS: In recent years in Yunnan Province, a notable proportion of vivax malaria patients are infected by P. vivax strains with a "K10 insertion" and partial sequence deletions in the promoter region of the pvcrt-o gene, necessitating vigilance.

Ultrasound-guided percutaneous peritoneal dialysis catheter insertion using multifunctional bladder paracentesis trocar: A modified percutaneous PD catheter placement technique.

BACKGROUND: To evaluate the efficacy and safety of ultrasound-guided percutaneous peritoneal dialysis catheter insertion using multifunctional bladder paracentesis trocar. METHODS: A retrospective review of 103 ESRD patients receiving percutaneous PD catheter insertion using a multifunctional bladder paracentesis trocar under ultrasound guidance at a single center between May 2016 and May 2018. Mechanical complications and catheter survival were evaluated over a 12-month follow-up. RESULT: Catheterization using this technique required only 10-30 minutes from the beginning of local anesthesia to the end of skin suture at the puncture site (mean 18 ± 7 minutes) and an incision length of 2-4 cm. Moreover, only four of 103 cases required catheter removal due to poor drainage within one month after surgery, with a success rate of 96.19%. Among failures, omentum wrapping was cause in two cases, catheter displacement in one case, and protein clot blockage in one case, while there were no instances of organ injury, severe hemorrhage, peritubular leakage, hernia, peritonitis, or exit infection within one month of PD catheter insertion. Catheter survival at 1 year was 92.2%. CONCLUSION: Percutaneous PD catheter insertion using a multifunctional bladder paracentesis trocar and ultrasound guidance is a feasible technique for ESRD patients.

Combining I148M and E167K variants to improve risk prediction for nonalcoholic fatty liver disease in Qingdao Han population, China.

BACKGROUND: PNPLA3 I148M variant and TM6SF2 E167K variant are recognized as the major genetic modifiers of nonalcoholic fatty liver disease (NAFLD). The present study sought to evaluate the potential additive effect of the two variants on the risk of NAFLD in Qingdao Han Population, China. METHODS: We genotyped PNPLA3 I148M variant and TM6SF2 E167K variant in a cohort of 512 unrelated NAFLD patients and 451 healthy controls by sequencing and polymerase chain reaction analysis. In addition, serum lipid profiles and liver enzymes were determined by standard clinical laboratory methods. RESULTS: The minor allele frequencies were 45.48% for PNPLA3 148 locus G allele and 6.69% for TM6SF2 167 locus T allele. The PNPLA3 I148M variant was significantly associated with the risk of NAFLD in an additive model (CG, OR = 2.092, 95% CI: 1.551-2.820, P = 0.000; GG, OR = 4.566, 95% CI: 3.141-6.638, P = 0.000, respectively). And, our data suggested a strong link between the TM6SF2 E167K variant and the risk of NAFLD in a dominant model (CT + TT, OR = 2.327, 95% CI: 1.542-3.513, P = 0.000). In addition, the increasing of the number of risk alleles were associated with the risk of NAFLD (1 risk allele, OR = 1.687, P = 0.001; 2 risk alleles, OR = 4.326, P = 0.000; 3 risk alleles, OR = 6.018, P = 0.027, respectively). CONCLUSIONS: Combining the I148M and E167K variants in a manner of an additive effect could improve risk prediction for NAFLD in a Qingdao Han Population cohort. TRIAL REGISTRATION: Chinese Clinical Trial Register.gov : ChiCTR1800015426.

Success rates and safety of a modified percutaneous PD catheter placement technique: Ultrasound-guided percutaneous placement of peritoneal dialysis catheters using a multifunctional bladder paracentesis trocar.

BACKGROUND: We modified the blind Seldinger technique by incorporating ultrasound guidance and the use of a multifunctional bladder paracentesis trocar for PD catheter (PDC) placement, which can be easily performed by a nephrologist and is a feasible technique. To compare success rates and safety of our modified percutaneous PD catheter placement technique to open surgery. METHODS: Two hundred and twelve stage-5 chronic kidney disease(CKD) patients receiving PD therapy from June 2016 to June 2019 were included, 105 patients treated by ultrasound-guided percutaneous placement of peritoneal dialysis catheters using a multifunctional bladder paracentesis trocar (Group A) and 107 patients receiving open surgical placement (Group B). Outcomes of patients via either catheter placement technique were retrospectively compared. The clinical success rate as defined by proper catheter drainage within 4 weeks after placement, complication rates (both technical complications and infections), and 1-year catheter survival were compared. RESULTS: There was no significant difference in sex ratio, age, or previous abdominal surgery history between groups (P > .05). Both surgical time and incision length were significantly shorter in Group A than in Group B (P < .05). Clinical success rate was also higher inGroup A (P < .05). Moreover, Group A demonstrated lower overall complication rates (P < .05) and lower incidence rates of early peritonitis, initial drainage disorder, and peritubular leakage (all P < .05). One-year catheter survival was also higher in Group A (P < .05). CONCLUSION: Percutaneous placement of PD catheters using our modified technique demonstrates superior success rates and safety compared to open surgery. In addition, our modified technique can be a better alternative to traditional Seldinger percutaneous catheterization for its higher success rate and safety, more accurate positioning.

A case report of cyclosporine-induced myopathy with subacute muscular atrophy as initial presentation.

RATIONALE: Cyclosporine A (CsA) is a potent immunosuppressive agent originally used to prevent rejection after organ transplantation but now more frequently used for treatment of refractory autoimmune diseases. It can induce adverse effects, such as nephrotoxicity, gastrointestinal reactions, and gingival hyperplasia whist myopathy with subacute muscular atrophy are rare. PATIENT CONCERNS: A 55-year-old male patient with idiopathic membranous nephropathy treated with cyclosporine A at 3 mg/kg/d and prednisone at 0.5 mg/kg.d for more than 20 days, gradually developed lower limb weakness, which were progressively aggravated until he was unable to stand or walk. A physical examination show muscle atrophy of both lower extremities, which was more severe in the right thigh muscle than the left, decreased muscular tension of the limbs was also observed. DIAGNOSES: Light microscopy and Transmission electron microscopy of muscle (quadriceps femoris) biopsy revealed drug-induced myopathy rather than neurogenic damage. INTERVENTIONS: Cyclosporine was withdrawn and replaced with cyclophosphamide tablets, prednisone remain unchanged and other symptomatic therapies were also administered. OUTCOMES: His bilateral thigh muscle atrophy showed improvement and lower limb weakness was obviously alleviated and he could stand and walk with the help of others 4 weeks later. Gradually, his thigh muscle atrophy was alleviated so that he was able to walk independently. After follow-up, no similar symptoms were found in the patients. LESSONS: CsA-induced myopathy with muscular atrophy is rare and serious, which can be identified according to pathological characteristics.