[Characteristics of serum autoantibodies in patients with lupus nephritis and tubulointerstitial damage].

OBJECTIVE: To observe the tubulointerstitial damage (TID) in lupus nephritis (LN) and investigate the relationship between autoantibodies and TID in lupus nephritis. METHODS: This cross-sectional study was conducted in a comprehensive tertiary hospital in Peking University Shenzhen Hospital. From March 2012 to July 2021, LN patients who performed renal biopsy were enrolled in the study. Clinical, laboratory and pathology data were collected. We classified the patients into none-or-mild group and moderate-to-severe groups according to the severity of interstitial fibrosis (IF) /tubular atrophy (TA) or tubulointerstitial inflammation (TII). The t test, U test and Chi-square test were used for statistical analysis as appropriate. RESULTS: A total of 226 patients were included, of who 190 (84%) were female with a median age of 32 (26, 39) years. 89% (201/226) of the patients who pathologically proved to be proliferative LN by renal biopsy. The frequency of moderate-to-severe TII and moderate-to-severe IF/TA was 30% (67/226) and 34% (76/226) respectively. For autoantibodies, the patients with moderate-to-severe TII had a lower rate of positive serum anti-ribonucleoprotein (anti-RNP) antibodies than the patients with none-or-mild TII (34% vs. 51%), and moderate-to-severe IF/TA had a lower rate of positive anti-ribosomal P protein (anti-P) antibodies than patients with none-or-mild IF/TA (19% vs. 33%). For other clinical indicators, the patients with moderate-to-severe TII and moderate-to-severe IF/TA were more often combined with proliferative LN, hypertension and anemia than the patients with none-or-mild TII and none-or-mild IF/TA, respectively. The patients with moderate-to-severe TII had higher serum creatinine values and lower glomerular filtration rates than the patients with none-or-mild TII. The patients with moderate-to-severe IF/TA had higher serum creatinine values, and lower glomerular filtration rates than the patients with none-or-mild IF/TA. CONCLUSION: In patients with LN in Southern China, anti-RNP antibodies and anti-P antibodies may be potential protective factors for TII and IF/TA, respectively. More studies are needed to identify the risk factors of lupus patients with TID and investigate the correlation between autoantibodies and TID, which are critical for developing better preventive and therapeutic strategies to improve the survival rate of LN.

Dynamic cervical flexion/extension atlantodental interval and functional outcome of the Harms technique for posterior C1/2 fixation: A retrospective analysis of 16 atlantoaxial subluxation cases in a tertiary medical center.

BACKGROUND: The aim of this study was to assess the relationship between the atlantodental interval (ADI) on dynamic flexion/extension cervical radiographs and functional outcomes of posterior spinal fixation by the Harms technique for atlantoaxial subluxation (AAS). Dynamic flexion/extension on cervical radiographs is a standard assessment for evaluation of C1/2 instability in AAS patients. Most studies focused on postoperative ADI and functional outcome, including pain and fusion rate; only few studies compared dynamic ADI change pre- to post-operatively. MATERIAL AND METHODS: Retrospectively, we reviewed the medical records of 16 patients who underwent posterior spinal fixation in our center from 2018 to 2019. We used dynamic cervical flexion/extension radiographs to assess the pre- to postoperative change at 12 months in ADI of flexion (ADIf), ADI of extension (ADIe), ADI between flexion/extension (ADIΔ), C1/2 fusion rate and functional outcomes measured by the modified Japanese Orthopaedic Association scale (mJOA scale). Postoperative CT at 3∼12 months assessed screw positioning on the Gertzbein and Robbins classification. RESULTS: In the 16 patients included in this study, ADIf, ADIe and ADIΔ were significantly reduced, from respectively 8.0mm, 5.0mm and 3.0mm preoperatively to 4.6mm, 3.8mm and 0.8mm at 12 months' follow-up. The fusion rate was 81% and the mJOA score recovery rate was 34.9±14.7%. Although the screw malposition rate was higher than in other studies in C1(10%) and C2(20%), there were no new neurologic deficits or worsening of symptoms at follow-up. CONCLUSIONS: The ADIΔ showed significant reduction, showing that the Harms technique of posterior spinal fixation can effective in maintaining the stability of the atlantoaxial joint and improving functional outcome.

[Development and evaluation of a machine learning prediction model for large for gestational age].

Objective: To develop and validate a useful predictive model for large gestational age (LGA) in pregnancy using a machine learning (ML) algorithm and compare its performance with the traditional logistic regression model. Methods: Data were obtained from the National Free Preconception Health Examination Project in China, carried out in 220 counties of 31 provinces from 2010 to 2012, covering all rural couples with a planned pregnancy. This study included all teams of childbearing age who delivered newborns within 24-42 weeks of gestational age and their newborns. Ten different ML algorithms were used to establish LGA prediction models, and the prediction performance of these models was evaluated. Results: A total of 104 936 newborns were included, including 54 856 boys (52.3%) and 50 080 girls (47.7%). The incidence of LGA was 11.7% (12 279). The imbalance between the two groups was addressed by the under- sampling technique, after which the overall performance of the ML models was significantly improved. The CatBoost model achieved the highest area under the receiver-operating-characteristic curve (AUC) value of 0.932. The logistic regression model had the worst performance, with an AUC of 0.555. Conclusions: In predicting the risk for LGA in pregnancy, the ML algorithms outperform the traditional logistic regression method. Compared to other ML algorithms, CatBoost could improve the performance, and it deserves further investigation.

Heterogeneity of anatomic regions by MR volumetry in juvenile myoclonic epilepsy.

OBJECTIVE: To investigate brain volumes in patients with well-characterized juvenile myoclonic epilepsy (JME). MATERIALS AND METHODS: We studied the MRI images of seventeen subjects with EEG and clinically defined JME and seventeen age- and sex-matched controls using voxel-based morphometry (VBM) and automated and manual volumetry. RESULTS: We found no significant group differences in the cortical volumes by automated techniques for all regions or for the whole brain. However, we found a larger pulvinar nucleus in JME using VBM with small volume correction and a larger thalamus with manual volumetry (P = 0.001; corrected two-tailed t-test). By analysing the individual subjects, we determined that considerable heterogeneity exists even in this highly selected group. Histograms of all JME and matched control regions' volumes showed more subjects with JME had smaller hippocampi and larger thalami (P < 0.05; chi-square). Subjects in whom the first seizure was absence were more likely to have smaller hippocampi than their matched control, while those without absences showed no differences (P < 0.05, chi-square). CONCLUSIONS: There is ample evidence for frontal cortical thalamic network changes in JME, but subcortical structural differences were more distinct in this group. Given the heterogeneity of brain volumes in the clinical population, further advancement in the field will require the examination of stringent genetically controlled populations.

Chlorogenic acid analogue S 3483: a potent competitive inhibitor of the hepatic and renal glucose-6-phosphatase systems.

S 3483, a synthetic derivative of chlorogenic acid (CHL), was found to be a reversible, linear competitive inhibitor of the glucose-6-phosphatase (Glc-6-Pase) system in rat renal microsomes and rat and human liver microsomes. The Ki for S 3483 in rat liver microsomes (129 nM) is three orders of magnitude smaller than the Ki for CHL. S 3483 up to 100 microM had no effect on the Glc-6-Pase enzyme activity or on the system inorganic pyrophosphatase activity (i.e., on T2, the Pi/inorganic pyrophosphate transporter). Thus, like CHL, S 3483 appears to be a site-specific inhibitor of T1, the Glc-6-P transporter of renal and liver microsomes. The potency of S 3483 was unaffected when the ratio Vmax(T1):Vmax(enzyme) was altered over a 10-fold range by applying enzyme inhibition and selective inactivation of T1. The absence of T1-imposed rate restrictions on the potency of reversible T1 inhibitors contrasts markedly with the response of reversible Glc-6-Pase enzyme inhibitors, whose potency declines sharply as T1 becomes more rate controlling. The potency of S 3483, but not of CHL, decreased as the microsomal protein concentration in the assay medium was increased. This effect suggests that as the protein concentration was raised the concentration of T1 in the assay medium approached the order of magnitude of the Ki for S 3483. Thus, the microsomal content of T1 is likely to be on the order of 100 pmol/mg protein. S 3483 is the most potent inhibitor of the Glc-6-Pase system reported to date. It and other tight-binding inhibitors of T1 will provide useful new tools for investigating the molecular structure and physiology/pathology of the Glc-6-Pase system.

Complement activation is a secondary rather than a causative factor in rabbit pulmonary artery ischemia/reperfusion injury.

We have previously demonstrated that reperfusion of a rabbit lung in vivo after 24 h of unilateral pulmonary artery occlusion results in edema, transient leukopenia, and intravascular leukocyte aggregation. We hypothesized that complement was activated by reperfusion and that this in turn contributed to lung injury. In the preliminary phase of the study, we found that ischemia followed by reperfusion resulted in a drop in C3 to 15 +/- 10% (mean +/- SEM) of the prereperfusion value as compared with no change in a group of control animals that had undergone an identical thoracotomy but without pulmonary artery occlusion and reperfusion (p less than 0.05). We then studied three groups of animals to determine if complement depletion with cobra venom factor (CVF) prior to ischemia and reperfusion would prevent the injury. Rabbits treated with CVF but without occlusion and reperfusion did not develop significant lung edema, with left and right lung wet/dry ratios of 5.32 +/- 0.11 and 5.26 +/- 0.12, respectively. For rabbits that were not treated with CVF but underwent ischemia and reperfusion, the comparable numbers were 6.15 +/- 0.36 and 5.19 +/- 0.32 (p less than 0.05 for right versus left). For CVF-treated rabbits that underwent ischemia and reperfusion, the right/left difference persisted (6.77 +/- 0.48 versus 5.35 +/- 0.14, p less than 0.01). Immunocytochemistry documented C3 deposition in non-CVF rabbits that underwent ischemia and reperfusion but not in CVF-treated rabbits. We conclude that ischemia/reperfusion of the lung results in complement activation, but it is not a complement-dependent injury.