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Background: To investigate whether the novel mutation of PKHD1 could cause polycystic kidney disease by affecting splicing with a recessive inheritance pattern., Methods: A nonconsanguineous Chinese couple with two recurrent pregnancies showed fetal enlarged echogenic polycystic kidney and oligoamnios were recruited. Pedigree WES, minigene splicing assay experiment and following bioinformatics analysis were performed to verify the effects, and inheritance pattern of diseasing-causing mutations., Results: WES revealed that both fetuses were identified as carrying the same novel mutation c.3592_3628 + 45del, p.? and c.11207 T>C, p.(Ile3736Thr) in the PKHD1 gene (NM_138694.4), which inherited from the father and mother respectively. Both bioinformatic method prediction and minigene splicing assay experience results supported the mutation c.3592_3628 + 45del, p.? affects the splicing of the PKHD1 transcript, resulting in exon 31 skipping. Another missense mutation c.11207 T>C, p.(Ile3736Thr) has a low frequency in populations and is predicted to be deleterious by bioinformatic methods., Conclusion: These findings provide a direct clinical and functional evidence that the truncating mutations of the PKHD1 gene could lead to more severe phenotypes, and cause ARPKD as a homozygous or compound heterozygous pattern. Our study broadens the variant spectrum of the PKHD1 gene and provides a basis for genetic counseling and diagnosis of ARPKD., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Zhang, Wu, Zhou, Liang, Han, Qi, Zhu, Yuan, Zhu and Zhai.)

Objective: To judge the type of acid-base balance disorder automatically according to the results of arterial blood gas analysis by using the IF function editing formula in an Excel spreadsheet., Methods: The four-step analysis was used to carry out programmatically through establishing acid-base balance disorder analysis process: (1) the acid and base types were determined according to pH value and the primary or main type of acid-base balance disorder was determined according to the pH value combined with blood carbon dioxide pressure (PaCO 2 ), HCO 3 - and their change rate; (2) the expected compensation formula was selected to determine whether there was mixed acid-base imbalance, according to the primary or main acid-base imbalance type; (3) the potential HCO 3 - should be calculated to replace the measured HCO 3 - when the primary acid-base imbalance was divided into two parts according to the prior two steps: respiratory acidosis or respiratory alkalosis accompanied with anion gap (AG) increased-metabolic acidosis and compared with the compensatory interval calculated by the predicted compensatory formula for acid or alkali to determine whether there were triple acid-base imbalance (TABD); (4) while the following two parts were judged: metabolic acidosis accompanied with AG increased-metabolic acidosis according to the prior two steps, ΔAG↑/ΔHCO 3 - ↓ should be calculated to determine whether there was metabolic alkalosis or metabolic acidosis with normal AG. The results of arterial blood gas analysis were judged by using the editing formula of IF function in Excel 2003 spreadsheet. A total of 96 patients admitted to the department of intensive care unit (ICU) of Xuzhou Central Hospital were enrolled. According to the results of arterial blood gas analysis, the type of acid-base imbalance of patients was judged by both artificial judgment (artificial group) and Excel spreadsheet automatic judgment (Excel spreadsheet group). The artificial group was composed by 2 associate chief physicians from neonatal intensive care unit (NICU) and 1 attending respiratory physician. If the results were inconsistent, the decision should be made after discussion. In the Excel spreadsheet group, data were input by one NICU attending physician and checked by another. The differences in the results and the time spent in judging the type of acid-base imbalance between the two groups were compared., Results: Forty-two types of acid-base imbalance were obtained by using the four-step analysis method and inputting relevant parameters such as pH, PaCO 2 , actual HCO 3 - , Na + , Cl - and compensation time limited into the Excel spreadsheet for blood gas analysis. Data analyses of 96 patients showed that the accuracy of using Excel spreadsheets to automatically determine the type of acid-base imbalance was higher than artificial group, but there was no statistically significant difference between the two groups [normal and simple acid-base imbalance: 100% (26/26) vs. 100% (26/26), mixed acid-base imbalance: 100% (51/51) vs. 96.08% (49/51), TABD: 100% (19/19) vs. 89.47% (17/19), all P > 0.05], and it took less time to judge the results of blood gas analysis by the Excel spreadsheet group compared with the artificial group (s: normal and simple acid-base imbalance: 31.13±4.70 vs. 74.20±16.53, mixed acid-base imbalance: 31.59±5.49 vs. 138.10±22.26, TABD: 30.98±5.40 vs. 308.40±78.12, all P < 0.01)., Conclusions: The automatic judging Excel spreadsheet with blood gas analysis can quickly and accurately determine the type of acid-base imbalance in arterial blood gas analysis.

We conducted this study to investigate the effects of the combination therapy of human chorionic gonadotropin (hCG) plus immunoglobulin (IG) on the levels of T helper 17 (Th17) cells and Foxp3 + regulatory T cells (Treg) in patients with unexplained recurrent spontaneous abortion (URSA). Twenty pregnant women with URSA underwent combination therapy of hCG plus IG. Flow cytometry was performed to measure the proportions of Th17 and Treg cells before and after treatment. RT-PCR and ELISA were applied to detect the concentrations of interleukin (IL)-17, IL-6, IL-10, and transforming growth factor (TGF)-β 1 in the peripheral blood. The therapy of hCG combined with IG may induce a decrease in the Th17/Treg ratio and the Treg bias, which may be beneficial for the maintenance of pregnancy. The levels of Th17 cells and related cytokines IL-17 and IL-6 decreased after the treatment (P<0.05). At the same time, levels of Treg cells and the related cytokines IL-10 and TGF-β 1 increased (P<0.05). The Th17/Treg ratio decreased significantly after treatment. In conclusion, the occurrence of URSA may be associated with the Th17/Treg balance disorder, and correcting the disorder may be one of the mechanisms behind the efficacy of combination therapy for URSA.