Machine learning in predicting T-score in the Oxford classification system of IgA nephropathy.

Background: Immunoglobulin A nephropathy (IgAN) is one of the leading causes of end-stage kidney disease (ESKD). Many studies have shown the significance of pathological manifestations in predicting the outcome of patients with IgAN, especially T-score of Oxford classification. Evaluating prognosis may be hampered in patients without renal biopsy. Methods: A baseline dataset of 690 patients with IgAN and an independent follow-up dataset of 1,168 patients were used as training and testing sets to develop the pathology T-score prediction (T pre) model based on the stacking algorithm, respectively. The 5-year ESKD prediction models using clinical variables (base model), clinical variables and real pathological T-score (base model plus T bio), and clinical variables and T pre (base model plus T pre) were developed separately in 1,168 patients with regular follow-up to evaluate whether T pre could assist in predicting ESKD. In addition, an external validation set consisting of 355 patients was used to evaluate the performance of the 5-year ESKD prediction model using T pre. Results: The features selected by AUCRF for the T pre model included age, systolic arterial pressure, diastolic arterial pressure, proteinuria, eGFR, serum IgA, and uric acid. The AUC of the T pre was 0.82 (95% CI: 0.80-0.85) in an independent testing set. For the 5-year ESKD prediction model, the AUC of the base model was 0.86 (95% CI: 0.75-0.97). When the T bio was added to the base model, there was an increase in AUC [from 0.86 (95% CI: 0.75-0.97) to 0.92 (95% CI: 0.85-0.98); P = 0.03]. There was no difference in AUC between the base model plus T pre and the base model plus T bio [0.90 (95% CI: 0.82-0.99) vs. 0.92 (95% CI: 0.85-0.98), P = 0.52]. The AUC of the 5-year ESKD prediction model using T pre was 0.93 (95% CI: 0.87-0.99) in the external validation set. Conclusion: A pathology T-score prediction (T pre) model using routine clinical characteristics was constructed, which could predict the pathological severity and assist clinicians to predict the prognosis of IgAN patients lacking kidney pathology scores.

Genome-Wide Association Study in Acute Tubulointerstitial Nephritis.

SIGNIFICANCE STATEMENT: Polymorphisms of HLA genes may confer susceptibility to acute tubulointerstitial nephritis (ATIN), but small sample sizes and candidate gene design have hindered their investigation. The first genome-wide association study of ATIN identified two significant loci, risk haplotype DRB1*14-DQA1*0101-DQB1*0503 (DR14 serotype) and protective haplotype DRB1*1501-DQA1*0102-DQB1*0602 (DR15 serotype), with amino acid position 60 in the peptide-binding groove P10 of HLA-DR ß 1 key. Risk alleles were shared among different causes of ATIN and HLA genotypes associated with kidney injury and immune therapy response. HLA alleles showed the strongest association. The findings suggest that a genetically conferred risk of immune dysregulation is part of the pathogenesis of ATIN. BACKGROUND: Acute tubulointerstitial nephritis (ATIN) is a rare immune-related disease, accounting for approximately 10% of patients with unexplained AKI. Previous elucidation of the relationship between genetic factors that contribute to its pathogenesis was hampered because of small sample sizes and candidate gene design. METHODS: We undertook the first two-stage genome-wide association study and meta-analysis involving 544 kidney biopsy-defined patients with ATIN and 2346 controls of Chinese ancestry. We conducted statistical fine-mapping analysis, provided functional annotations of significant variants, estimated single nucleotide polymorphism (SNP)-based heritability, and checked genotype and subphenotype correlations. RESULTS: Two genome-wide significant loci, rs35087390 of HLA-DQA1 ( P =3.01×10 -39 ) on 6p21.32 and rs2417771 of PLEKHA5 on 12p12.3 ( P =2.14×10 -8 ), emerged from the analysis. HLA imputation using two reference panels suggested that HLA-DRB1*14 mainly drives the HLA risk association . HLA-DRB1 residue 60 belonging to pocket P10 was the key amino acid position. The SNP-based heritability estimates with and without the HLA locus were 20.43% and 10.35%, respectively. Different clinical subphenotypes (drug-related or tubulointerstitial nephritis and uveitis syndrome) seemed to share the same risk alleles. However, the HLA risk genotype was associated with disease severity and response rate to immunosuppressive therapy. CONCLUSIONS: We identified two candidate genome regions associated with susceptibility to ATIN. The findings suggest that a genetically conferred risk of immune dysregulation is involved in the pathogenesis of ATIN.

Facile synthesis, crystal structure, quantum calculation, and biological evaluations of novel selenenyl sulfide compounds as potential agrochemicals.

BACKGROUND: In order to design compounds with fresh molecular skeleton to break through the limitation of available agrochemicals, a series of 36 novel selenenyl sulfide compounds were chemically synthesized, and their biological activities were fully evaluated against tobacco mosaic virus (TMV), 14 plant pathogenic fungi, three insect species and plant acetohydroxyacid synthase (AHAS). RESULTS: All the target compounds were characterized by proton nuclear magnetic resonance (1 H-NMR), carbon-13 (13 C)-NMR, selenium-77 (77 Se)-NMR, and high-resolution mass spectrometry (HRMS). The crystal structure of 10j indicated that the Se-S bond was successfully constructed. Compounds 10d, 10h, 10s, 10u, 10aa, 10ac, 10ae, 10ag, and 10ai exhibited 40%, 43%, 39%, 41%, 47%, 46%, 47%, 42%, and 39% anti-TMV activities at 500 mg L-1 , better than that of ribavirin. The median effective concentration (EC50 ) against Sclerotinia sclerotiorum of 10ac was 6.69 mg L-1 and EC50 values against Physalospora piricola and Pyricularia grisea of 10z were 12.25 mg L-1 and 15.27 mg L-1 , respectively, superior to the corresponding values of chlorothalonil. Compounds 10c and 10v demonstrated 100% larvicidal activity against Culex pipiens pallens at 5 mg L-1 , while 10a displayed 100% insecticidal activity against Mythimna separata at 200 mg L-1 . Compounds 10c, 10j, and 10o showed > 60% inhibitions against plant AHAS at 10 µmol L-1 . From the quantum calculation, highest occupied molecular orbital (HOMO) was considered as a factor that affects the anti-TMV activity. CONCLUSION: The preliminary results suggested that more efforts should be devoted to exploring the selenenyl sulfides for the discovery of new leads of antiviral agent, fungicide, insecticide or AHAS inhibitors as potential agrochemicals for crop protection. © 2023 Society of Chemical Industry.

Agreement of infrared ear temperature with nasopharyngeal temperature and diagnostic performance on hypothermia in general anesthetized patients.

BACKGROUND: Infrared ear thermometry is widely used in clinical practice due to its noninvasive, convenient, and quick sampling. However, its accuracy and feasibility in anesthetized patients have not yet been established. METHODS: We conducted this cross-sectional study to evaluate the agreement between infrared ear temperature and nasopharyngeal temperature in general anesthetized patients and its performance in intraoperative hypothermia, defined as nasopharyngeal temperature <36°C. Adult female patients who underwent gynecological surgery under general anesthesia were enrolled in this study. Infrared ear temperature by Braun ThermoScan PRO 4000 (Braun GmbH, Kronberg, Germany) and nasopharyngeal temperature were measured simultaneously before, during, and after surgery. The agreement between the two temperatures was assessed using the intraclass correlation coefficient (ICC) and Bland-Altman analysis. The diagnostic performance of the infrared ear thermometer for hypothermia was evaluated using receiver operating characteristic (ROC) curve analysis. RESULTS: Fifty-six patients with 168 pairs of simultaneous infrared ear and nasopharyngeal temperatures were included in this analysis. The mean infrared ear temperature was consistently higher than the nasopharyngeal temperature throughout surgery, but the differences were small (0.22, 0.13, and 0.06°C before, during, and after surgery, respectively). The ICC between the two temperatures before, during, and after surgery was 0.70, 0.75, and 0.80, respectively, and 93.5% of the differences fell within the 95% limits of agreement of ±0.5°C. An infrared ear thermometer had high diagnostic accuracy for hypothermia, with an area under the ROC curve of 0.95 (95% confidence interval [CI], 0.92-0.98). The cutoff of infrared ear temperature for hypothermia was 36.2°C with a sensitivity of 0.89 (95% CI, 0.71-0.98) and a specificity of 0.87 (95% CI, 0.81-0.92). CONCLUSION: The infrared ear temperature is in good agreement with the nasopharyngeal temperature in general anesthetized patients without hyperthermia and has high performance for detecting hypothermia. An infrared ear thermometer can be a diagnostic tool for intraoperative hypothermia.

Feasibility of immediate removal of urinary catheter after laparoscopic gynecological surgery for benign diseases: A meta-analysis of randomized controlled trials.

BACKGROUND: The proper time for removing the urinary catheter after gynecologic laparoscopy is unclear. OBJECTIVES: To assess the feasibility of immediate catheter removal after benign gynecologic laparoscopy. SEARCH STRATEGY: PubMed, Embase, Web of Science, Cochrane Central Register of Controlled Trials, and Wanfang Data were searched from inception to November 30, 2021. SELECTION CRITERIA: Only randomized controlled trials published in English or Chinese comparing immediate versus delayed catheter removal after gynecologic laparoscopy for benign diseases were included. DATA COLLECTION AND ANALYSIS: The primary outcome was the incidence of postoperative urinary retention (PUR). A random effects model was used to calculate pooled relative risk (RR) and 95% confidence interval (CI). MAIN RESULTS: Six studies were included in this meta-analysis. There was no significant difference in PUR between immediate and delayed catheter removal (RR 1.51, 95% CI 0.37-6.18), but the evidence was of very low quality. Subgroup analysis according to the type of surgery showed a higher rate of PUR with immediate removal after hysterectomy than after other surgeries. Immediate removal was associated a lower incidence of urinary tract infection and a shorter time to mobilization compared with delayed removal. CONCLUSIONS: Immediate removal of the urinary catheter is feasible and beneficial after benign gynecologic laparoscopy.

CD24 genetic variants contribute to overall survival in patients with gastric cancer.

AIM: To investigate the role of single nucleotide polymorphisms (SNPs) in CD24 gene in susceptibility and overall survival of gastric cancer (GC). METHODS: We genotyped 3 tagging SNPs of CD24-P-534 in the promoter region, P170 in the coding region of exon 2 and P1527 in the 3' untranslated region - using polymerase chain reaction-restriction fragment length polymorphism in specimens from 679 histologically-confirmed GC cases, 111 gastric atrophy (GA) cases and 976 tumor-free controls. Serum immunoglobulin G antibodies to Helicobacter pylori (H. pylori) of all subjects were detected by enzyme-linked immunosorbent assay. CD24 expression was evaluated by immunohistochemistry in 131 GC specimens. Correlations between SNPs and risk of GC or GA were shown by P values and odd ratios (ORs) with 95% confidence intervals (95%CI) compared with the most common genotype of each SNP using the unconditional logistic regression model after adjusting for age, sex and H. pylori infection. Survival within each SNP group was plotted by Kaplan-Meier method and compared by log-rank test (recessive model). Hazard ratios with 95%CIs were computed by Cox regression model after adjusting for age, sex, histological type, tumor differentiation, clinical stage and post-operational chemotherapy. RESULTS: All of the three loci were in Hardy-Weinberg equilibrium in the control group. Median follow-up time for the 600 GC patients included in the survival analysis was 36.2 mo (range, 2.1-66.7 mo; 95%CI: 34.3-36.5 mo). Patients with the P-534 A/A genotype had significantly shorter survival (HR = 1.38, 95%CI: 1.01-1.88, P = 0.042) than did the C/C or C/A genotype carriers after adjusting for age, sex, histological type, tumor differentiation, clinical stage and post-operational chemotherapy. This trend was more evident in patients who lived longer than 2.5 years (HR = 7.55, 95%CI: 2.16-26.32, P = 0.001). The P170 T/T genotype was associated with a shorter lifespan than the non-T/T genotypes, but not significantly so. None of the three genetic variants was found to be associated with risk of GC (including tumor stage, grade and distant metastasis) or with risk of gastric atrophy. Furthermore, no difference of CD24 expression was found among the genotypes. CONCLUSION: The P-534 site in CD24 gene affects the overall survival of gastric cancer and may serve as a prognostic marker for gastric cancer.

The Dose-response of Intrathecal Ropivacaine Co-administered with Sufentanil for Cesarean Delivery under Combined Spinal-epidural Anesthesia in Patients with Scarred Uterus.

BACKGROUND: Spinal anesthesia is considered as a reasonable anesthetic option in lower abdominal and lower limb surgery. This study was to determine the dose-response of intrathecal ropivacaine in patients with scarred uterus undergoing cesarean delivery under combined spinal-epidural anesthesia. METHODS: Seventy-five patients with scarred uterus undergoing elective cesarean delivery under combined spinal-epidural anesthesia were enrolled in this randomized, double-blinded, dose-ranging study. Patients received 6, 8, 10, 12, or 14 mg intrathecal hyperbaric ropivacaine with 5 µg sufentanil. Successful spinal anesthesia was defined as a T4sensory level achieved with no need for epidural supplementation. The 50% effective dose (ED50) and 95% effective dose (ED95) were calculated with a logistic regression model. RESULTS: ED50and ED95of intrathecal hyperbaric ropivacaine for patients with scarred uterus undergoing cesarean delivery under combined spinal-epidural anesthesia (CSEA) were 8.28 mg (95% confidence interval [CI]: 2.28-9.83 mg) and 12.24 mg (95% CI: 10.53-21.88 mg), respectively. CONCLUSION: When a CSEA technique is to use in patients with scarred uterus for an elective cesarean delivery, the ED50and ED95of intrathecal hyperbaric ropivacaine along with 5 µg sufentanil were 8.28 mg and 12.24 mg, respectively. In addition, this local anesthetic is unsuitable for emergent cesarean delivery, but it has advantages for ambulatory patients.

miR-200a inhibits tumor proliferation by targeting AP-2γ in neuroblastoma cells.

BACKGROUND: MicroRNA-200a (miR-200a) has been reported to regulate tumour progression in several tumours but little is known about its role in neuroblastoma. Our aim was to investigate the potential role and mechanism of miR-200a in neuroblastomas. MATERIALS AND METHODS: Expression levels of miR-200a in tissues were determined using RT-PCR. The effect of miR-200a and shAP-2γ on cell viability was evaluated using MTS assays, and target protein expression was determined using Western blotting and RT-PCR. Luciferase reporter plasmids were constructed to confirm direct targeting. RESULTS were reported as mean±S.E.M and differences were tested for significance using the 2-tailed Students t-test. RESULTS: We determined that miR-200a expression was significantly lower in neuroblastoma tumors than the adjacent non-cancer tissue. Over-expression of miR-200 are reduced cell viability in neuroblastoma cells and inhibited tumor growth in mouse xenografts. We identified AP-2γ as a novel target for miR-200a in neuroblastoma cells. Thus miR-200a targets the 3'UTR of AP-2γ and inhibits its mRNA and protein expression. Furthermore, our result showed that shRNA knockdown of AP-2γ in neuroblastoma cells results in significant inhibit of cell proliferation and tumor growth in vitro, supporting an oncogenic role of AP-2γ in neuroblastoma. CONCLUSIONS: Our study revealed that miR-200a is a candidate tumor suppressor in neuroblastoma, through direct targeting of AP-2γ. These findings re-enforce the proposal of AP-2γ as a therapeutic target in neuroblastoma.

Synthesis and characteristics of (Hydrogenated) ferulic acid derivatives as potential antiviral agents with insecticidal activity.

BACKGROUND: Plant viruses cause many serious plant diseases and are currently suppressed with the simultaneous use of virucides and insecticides. The use of such materials, however, increases the amounts of pollutants in the environment. To reduce environmental contaminants, virucides with insecticidal activity is an attractive option. RESULTS: A series of substituted ferulic acid amide derivatives 7 and the corresponding hydrogenated ferulic acid amide derivatives 13 were synthesized and evaluated for their antiviral and insecticidal activities. The majority of the synthesized compounds exhibited good levels of antiviral activity against the tobacco mosaic virus (TMW), with compounds 7a, 7b and 7d in particular providing higher levels of protective and curative activities against TMV at 500 µg/mL than the control compound ribavirin. Furthermore, these compounds displayed good insecticidal activities against insects with piercing-sucking mouthparts, which can spread plant viruses between and within crops. CONCLUSIONS: Two series of ferulic acid derivatives have been synthesized efficiently. The bioassay showed title compounds not only inhibit the plant viral infection, but also prevented the spread of plant virus by insect vectors. These findings therefore demonstrate that the ferulic acid amides represent a new template for future antiviral studies.

A randomized comparison of caudal block by sacral hiatus injection under ultrasound guidance with traditional sacral canal injection in children.

BACKGROUND: There is a risk of inadvertent dural or vascular puncture for the traditional single-shot caudal block performed by inserting the needle into the sacral canal through the sacral hiatus. This prospective, randomized study was to evaluate the clinical feasibility of the hiatus injection under ultrasound guidance for caudal block in children. METHODS: 140 ASA I-II children undergoing inguinal hernia repair were randomly allocated to one of two groups (Group C or Group H, n = 70). 1 ml·kg(-1) of 0.25% ropivacaine was injected after the needle was inserted into the sacral canal in Group C, or after the needle pierced the sacrococcygeal ligament under a transverse ultrasound view in Group H. Success rate of block, puncture frequency, complications, and durations of block were recorded. RESULTS: The success rate of block was similar between two groups (95.7% in Group C vs 92.8% in Group H, P > 0.05). The first puncture success rate was higher, and the durations of block were shorter in Group H than in Group C (92.8% vs 60% and 145 ± 23s vs 164 ± 31s, respectively P < 0.05). Bloody puncture had an incidence of 18.6% in Group C and 5.7% in Group H (P < 0.05). Subcutaneous bulging occurred in six patients (7.1%) in Group C but none in Group H (P < 0.05). CONCLUSIONS: Sacral hiatus injection offers a reliable caudal block for pediatric inguinal hernia repair with the advantages of easier performance and fewer complications compared with traditional sacral canal injection.

Influence of epidural dexamethasone on maternal temperature and serum cytokine concentration after labor epidural analgesia.

OBJECTIVE: To evaluate the effects of epidural dexamethasone on maternal temperature and serum cytokine levels after labor epidural analgesia. METHODS: Sixty healthy term nulliparas in spontaneous labor were randomized to receive epidural analgesia alone using bupivacaine 0.125% and fentanyl 1 µg/mL (group I) or epidural analgesia combined with dexamethasone 0.2mg/mL (group II) (n=30 per group). Maternal tympanic temperature was measured before epidural analgesia and hourly thereafter until delivery. Maternal and cord venous blood were sampled for analysis of interleukin-6 (IL-6), tumor necrosis factor-α, and interleukin-10 levels. RESULTS: There was no difference in the incidence of intrapartum fever (38 °C or more) between the 2 groups (3/30 versus 1/30, P=0.612). The mean maternal temperature increased with time in group I, with the elevation reaching statistical significance at 4 hours post analgesia and at delivery compared with baseline (P=0.012 and P=0.043, respectively). A similar trend was observed with maternal serum IL-6 levels in group I. In group II, maternal temperature and IL-6 levels did not differ from baseline at any time point during labor. CONCLUSION: Epidural dexamethasone alleviates maternal temperature elevation after epidural analgesia. This effect can be attributed to the decrease in IL-6 levels.

Polymorphisms in prostate-specific antigen (PSA) gene, risk of prostate cancer, and serum PSA levels in Japanese population.

Recent studies have indicated that the prostate-specific antigen (PSA) gene polymorphisms may be associated with the risk of prostate cancer in Caucasian populations. To verify the association, we examined the PSA polymorphisms at positions -158 and -252 in 300 prostate cancer cases, 216 benign prostatic hyperplasia (BPH) cases, and 266 controls by the PCR-restriction fragment length polymorphism analysis. Regarding the PSA polymorphism at position -158, the A allele was less common in the Japanese population (A 0.22, G 0.78) than that in other ethnic populations (A 0.37-0.52, G 0.48-0.63). No significant associations were found between the polymorphism and the risks of prostate cancer (P=0.530) and BPH (P=0.740) and between the polymorphism and the serum PSA level (P=0.626). As for the polymorphism at position -252, no significant results were also found. In conclusion, the PSA polymorphisms may not be associated with the risk of prostate cancer development and its disease progression and the risk of BPH in Japanese men, and may also be not related to the serum PSA level in Japanese men with prostate cancer.