A lissencephaly-associated BAIAP2 variant causes defects in neuronal migration during brain development.

Lissencephaly is a neurodevelopmental disorder characterized by a loss of brain surface convolutions caused by genetic variants that disrupt neuronal migration. However, the genetic origins of the disorder remain unidentified in nearly one-fifth of people with lissencephaly. Using whole-exome sequencing, we identified a de novo BAIAP2 variant, p.Arg29Trp, in an individual with lissencephaly with a posterior more severe than anterior (P>A) gradient, implicating BAIAP2 as a potential lissencephaly gene. Spatial transcriptome analysis in the developing mouse cortex revealed that Baiap2 is expressed in the cortical plate and intermediate zone in an anterior low to posterior high gradient. We next used in utero electroporation to explore the effects of the Baiap2 variant in the developing mouse cortex. We found that Baiap2 knockdown caused abnormalities in neuronal migration, morphogenesis and differentiation. Expression of the p.Arg29Trp variant failed to rescue the migration defect, suggesting a loss-of-function effect. Mechanistically, the variant interfered with the ability of BAIAP2 to localize to the cell membrane. These results suggest that the functions of BAIAP2 in the cytoskeleton, cell morphogenesis and migration are important for cortical development and for the pathogenesis of lissencephaly in humans.

Case report: 177Lu DOTA-TATE: a new scheme for the treatment of prostate neuroendocrine cancer.

Background: Most instances of small cell carcinoma originate from the lungs, while the gastrointestinal tract serves as a secondary site. Only a minuscule proportion of cases manifest within the urogenital system. Prostate small cell carcinoma (SCCP) represents an exceedingly uncommon pathological subtype within the realm of prostate cancer, displaying significant rarity in clinical settings. This scarcity has resulted in a paucity of adequate foundational and clinical research for SCCP treatment. While investigations have unveiled a certain therapeutic efficacy of radiotherapy and chemotherapy for SCCP, clinical practice has revealed suboptimal treatment outcomes. We hereby present a case report detailing the utilization of 177Lu-DOTA-TATE in the treatment of SCCP, aiming to investigate the therapeutic efficacy of 177Lu-DOTA-TATE for SCCP. Case presentation: A male patient in his 80s presented with elevated prostate-specific antigen (PSA) levels and underwent a biopsy that revealed prostate adenocarcinoma. The patient received CAB (bicalutamide + goserelin) therapy. One year later, disease progression was detected, and a second biopsy confirmed the presence of prostate small cell carcinoma. Following the diagnosis of prostate small cell carcinoma, the patient underwent two cycles of 177Lu-DOTA-TATE treatment. Subsequent to the treatment, the original lesions showed shrinkage, metastatic lesions disappeared, and there was significant improvement, approaching complete remission. Conclusion: SCCP exhibits a high degree of malignancy and aggressive invasiveness, currently lacking effective therapeutic modalities. The treatment course of this patient serves as compelling evidence for the efficacy of 177Lu-DOTA-TATE in managing SCCP, thereby opening new avenues for future SCCP treatments.

[Evaluation and Source Analysis of Heavy Metal Pollution in Sediments of the Yellow River Basin Based on Monte Carlo Simulation and PMF Model].

As sediment is an essential component of rivers, the enrichment of heavy metals in sediment presents a serious threat to the aquatic environment. Many industrial cities are located along the Yellow River, and heavy metal pollution is a prominent problem in these areas. Thus, the study of heavy metal pollution in sediments of the Yellow River basin is of vital significance to the safety of the Yellow River basin ecosystem. In this study, we collected data on the concentrations of heavy metals (Pb, Cd, Cr, As, Zn, Cu, Ni, and Hg) in the sediments of the Yellow River basin from 2000 to 2020. We first analyzed the spatial distribution characteristics of heavy metals based on descriptive statistics and geostatistics and then used the Monte Carlo method to evaluate the probability of the ground accumulation index(Igeo), potential ecological risk, and toxicity units. Finally, the number of pollution sources and their contribution rates were determined by combining the positive definite matrix factor (PMF) decomposition model and Pearson correlation analysis. It was found that the mean values of ω(Pb), ω(As), ω(Zn), ω(Ni), ω(Cu), ω(Hg), ω(Cr), and ω(Cd) in the Yellow River basin sediments were 26.92, 11.78, 87.17, 31.13, 24.96, 0.07, 73.36, and 0.58 mg·kg-1, which exceeded the mean soil background values in the Yellow River basin provinces by 1.27, 1.08, 1.26, 1.05, 1.09, 2.32, 1.14, and 5.95 times, respectively, among which Cd exceeded the standard by the largest factor and should be taken seriously. The Igeo was ranked as Cd>Hg>Cr>Cu>Pb>Zn>As>Ni, and Cd and Hg showed medium-severe pollution. The proportions of heavy ecological risk in sediments in the upper, middle, and lower reaches of the Yellow River basin were 18.6%, 15.7%, and 7.1%, respectively, with a decreasing trend. Heavy metals in the sediments of the Yellow River basin were in a low-toxicity state. The PMF-Pearson correlation analysis showed that the four sources of heavy metals in the Yellow River basin sediments were mining sources (42.2%), natural activities (38.3%), agricultural activities (11.6%), and electroplating wastewater (7.9%). The results of this study can provide a basis for developing relevant pollution prevention and control measures in the Yellow River basin.

Efficacy of Whole-Blood Exchange Transfusion in Refractory Severe Autoimmune Haemolytic Anaemia Secondary to Systemic Lupus Erythematosus: A Real-World Observational Retrospective Study.

Background: Severe autoimmune haemolytic anaemia (AIHA) in systemic lupus erythematosus (SLE) patients could be life-threatening and formidable, especially in those nonresponsive to glucocorticoids (GCs) and immunosuppressants (ISAs). Whole-blood exchange transfusion (WBE), with plasma exchange and pathogenic cell removal as well as healthy red blood cell transfusion, could be beneficial. The objective of this study was to investigate the efficacy and safety of WBE in combination with GCs/ISAs. Methods: In this retrospective study, the clinical data of 22 refractory severe SLE-AIHA inpatients between February 2016 and February 2021 were collected and analysed, among whom 14 patients had received WBE and were compared with those treated with typical second-line therapy of intravenous immunoglobulin and/or rituximab (IVIG/RTX). Results: Among the 22 severe refractory SLE-AIHA patients, eight patients received IVIG and/or RTX without WBE (group 1, IVIG/RTX, n = 8), seven patients were given WBE without IVIG/RTX (group 2, WBE alone, n = 7), and seven patients who failed initial IVIG/RTX therapy were given sequential WBE therapy (group 3 IVIG/RTX→WBE, n = 7). Fourteen patients had accepted WBE treatment regardless of prior IVIG/RTX usage (group 2 + 3, WBE ± IVIG/RTX, n = 14). On days 1, 3, 5, and 7 after corresponding therapies, patients of groups 2, 3, and 2 + 3 showed significantly higher levels of haemoglobin (Hb) than patients of group 1. Compared with patients of group 1, patients of groups 2, 3, and 2 + 3 took less time to reach and maintain Hb ≥60 g/L from baseline. Groups 2 and 2 + 3 consumed a lower dose of GCs than group 1 to reach and maintain Hb ≥60 g/L from baseline. Group 1 experienced longer hospital stays than group 2, and group 3's cost of hospitalisation is more than groups 1 and 2. Hbmin <40 g/L may be a key indicative factor for initiating WBE remedy therapy as IVIG/RTX may not be effective enough in 48-72 h in those patients with refractory severe SLE-AIHA. No severe adverse effects were observed in the WBE group. Conclusions: WBE could be a safe and beneficial alternative therapy for refractory severe SLE-AIHA.

Multimode Computed-Tomography-Guided Thrombolysis under a Prolonged Time Window in Acute Ischemic Stroke Patients with Atrial Fibrillation.

Atrial fibrillation (AF) is an independent risk factor for intracranial hemorrhage in patients receiving recombinant-tissue-type plasminogen activator (rt-PA) thrombolytic therapy. Research showed that patients with acute ischemic stroke (AIS) could benefit from multimode computed-tomography- (CT-) guided intravenous thrombolysis over 4.5 hours. The medical data of patients with AIS in our center were retrospectively reviewed, and the data of the multimode CT-guided thrombolytic therapy or nonthrombolytic therapy within different time windows (3-9 hours) were evaluated. 134 AIS cases were selected successfully and divided into three groups: patients with AF treated by rt-PA (AF rt-PA), patients with AF not treated by rt-PA (AF non-rt-PA), and patients without AF treated by rt-PA (non-AF rt-PA). After correcting for the baseline NIH Stroke Scale (NIHSS), sex, age, and hypertension data, the comparison results showed that the NIHSS improved significantly at hospital discharge for rt-PA-treated patients (n = 47) compared to non-rt-PA-treated patients with AIS (n = 31) with AF (P = 0.0156). The NIHSS evaluation at 90 days of follow-up also improved in rt-PA-treated patients (P = 0.0157). The NIHSS at hospital discharge was higher in AF rt-PA-treated patients compared to non-AF rt-PA-treated patients (P = 0.0167) after correction; the difference was not statistically significant at 90 days of follow-up (P = 0.091). Our research showed that the neural function improved after 3-9 hours of thrombolytic therapy with rt-PA in patients with AIS and AF. If there is no thrombolytic taboo, the patients could benefit from the thrombolytic therapy, although the onset time window has been extended to 9 hours.

[Inhibition of SRC-1 expression in prostate cancer cells by RNAi and its significance].

OBJECTIVE: To investigate the inhibition of the expression of steroid receptor coactivator-1 (SRC-1) in the LNCap cell line through RNA interference (RNAi) and the effect of the silenced SRC-1 gene on LNCap cells. METHODS: The experiment included four groups: siRNA transfection, siRNA negative control, bland vehicle (with Lipofectamine 2000 but no siRNA), and blank control (with neither Lipofectamine 2000 nor siRNA). LNCap cells were transfected with designed siRNA using the liposomes method, the expressions of SRC-1 determined by Q-PCR and Western blot, and the proliferation of the LNCap cells detected by the CCK-8 method. RESULTS: The expression of SRC-1 mRNA in the transfected LNCap cells was decreased by 35% at 24 hours and 77% at 48 hours, with statistically significant differences from the blank control group (P < 0.05). The SRC-1 protein expression of the transfected group was 0.359 +/- 0.034 at 24 hours and 0.257 +/- 0.065 at 48 hours, markedly decreased as compared with that of the negative control (0.782 +/- 0.078 and 0.766 +/- 0.043) , bland vehicle (0.840 +/- 0.013 and 0.786 +/- 0.051), and blank control group (0.816 +/- 0.065 and 0.805 +/- 0.107) (P < 0.05). The LNCap cell growth inhibition rates were 25%, 52%, 55% and 60% at 24, 48, 72 and 96 hours, respectively. CONCLUSION: The expression of SRC-1 is correlated with the growth of LNCap cells; its high expression in androgen-independent prostate cancer cells may be involved in the progression to androgen-independence. Inhibiting the expression of SRC-1 may be an option for the treatment of androgen-dependent prostate cancer.

[The meaning of "nue" and "gu" in the Five Classical Canons and Huangdi Neijing (Yellow Emperor's Inner Canon)].

There were many terms of traditional Chinese medicine (TCM) in the Confucian Five Classical Canons, such as nue and gu. Among them, nue had the meaning of "sudden disease" or "cold disease" in the Spring and Autumn Period, which were changed to a name of disease, nue disease in the Warring States Period. In the Huangdi Neijing (Yellow Emperor's Inner Canon), there was a special treatise to discuss it. The original meaning of gu was poisonous insect, and then was explicated to a insect causing harm to people. Therefore, gu had the meaning of gathering gu for harming people, gu disease, gu poison and bug in the abdomen. Gu was recorded as a divinatory symbols in the Zhou Yi (The Book of Change), explained as a disease of heart-spirit confusion by later generations. Also, it was recorded in the Zuo Zhuan (The Commentary of Zuo Qiuming) and Huangdi Neijing.

Risk factors for sporadic colorectal cancer in southern Chinese.

AIM: To investigate the role of smoking, alcohol drinking, family history of cancer, and body mass index (BMI) in sporadic colorectal cancer in southern Chinese. METHODS: A hospital-based case-control study was conducted from July 2002 to December 2008. There were 706 cases and 723 controls with their sex and age (within 5 years) matched. An unconditional logistic regression model was used to analyze the association between smoking, alcohol drinking, family history of cancer, BMI and sporadic colorectal cancer. RESULTS: No positive association was observed between smoking status and sporadic colorectal cancer risk. Compared with the non alcohol drinkers, the current and former alcohol drinkers had an increased risk of developing sporadic colorectal cancer (CRC) (adjusted OR = 8.61 and 95% CI = 6.15-12.05; adjusted OR = 2.30, 95% CI = 1.27-4.17). Moreover, the increased risk of developing sporadic CRC was significant in those with a positive family history of cancer (adjusted OR = 1.62, 95% CI = 1.12-3.34) and in those with their BMI >or= 24.0 kg/m(2) (adjusted OR = 1.39, 95% CI = 1.10-1.75). Stratification analysis showed that the risk of developing both colon and rectal cancers was increased in current alcohol drinkers (adjusted OR = 7.60 and 95% CI = 5.13-11.25; adjusted OR = 7.52 and 95% CI = 5.13-11.01) and in those with their BMI >or= 24.0 kg/m(2) (adjusted OR = 1.38 and 95% CI = 1.04-1.83; adjusted OR = 1.35 and 95% CI = 1.02-1.79). The risk of developing colon cancer, but not rectal cancer, was found in former alcohol drinkers and in those with a positive family history of cancer (adjusted OR = 2.51 and 95% CI = 1.24-5.07; adjusted OR = 1.82 and 95% CI = 1.17-2.82). CONCLUSION: Alcohol drinking, high BMI (>or= 24.0 kg/m(2)) and positive family history of cancer are the independent risk factors for colorectal cancer in southern Chinese.

[Analysis of mortality trend of cancer from 1980 to 2002 in Linqu County Shandong Province].

OBJECTIVE: To investigate the trend of total cancer mortality in Linqu County Shandong Province from 1980 to 2002. METHODS: A retrospective survey on all causes of death in 1980 - 1982, 1990 - 1992 and 2000 - 2002 was conducted in Linqu County, a high risk area of gastric cancer in Northeast of China, respectively. RESULTS: The cancer death, was found the third leading cause of death in 1980 - 1982 in Linqu County, and the second to that of vascular disease in 2000 - 2002. The cancer mortality (standardized mortality) was 108.97/100,000 (111.48/100,000), 132.38/100,000 (127.94/100,000) and 148.48/100,000 (105.53/100,000) in 1980 - 1982, 1990 - 1992 and 2000 - 2002, respectively. The trend of cancer mortality was significantly increased (Z = 13.42, P < 0.0001). The added cancer-eliminated life expectancy in three periods was 2.46 years, 3.29 years and 3.76 years in male (F = 13.99, P < 0.0001), and 1.67 years, 2.30 and 2.33 years in female (F = 13.61, P < 0.0001), respectively. The standardized mortality of gastric cancer (percentage in all cancer death) was 44.93/100,000 (40.29%), 41.37/100,000 (32.34%) and 27.73/100,000 (26.90%) in 1980 - 1982, 1990 - 1992 and 2000 - 2002, respectively. The trend of gastric cancer standardized mortality was significantly reduced (Z = 6.35, P < 0.01). CONCLUSION: The mortality of cancer in Linqu County has been increased from 1980 to 2002, but no such trend was found after adjusting ages. However, there was a decreased trend on standardized mortality of gastric cancer in the past 20 years.