Multiple serum anti-glutamate receptor antibody levels in clozapine-treated/naïve patients with treatment-resistant schizophrenia.

BACKGROUND: Glutamatergic function abnormalities have been implicated in the etiology of treatment-resistant schizophrenia (TRS), and the efficacy of clozapine may be attributed to its impact on the glutamate system. Recently, evidence has emerged suggesting the involvement of immune processes and increased prevalence of antineuronal antibodies in TRS. This current study aimed to investigate the levels of multiple anti-glutamate receptor antibodies in TRS and explore the effects of clozapine on these antibody levels. METHODS: Enzyme linked immunosorbent assay (ELISA) was used to measure and compare the levels of anti-glutamate receptor antibodies (NMDAR, AMPAR, mGlur3, mGluR5) in clozapine-treated TRS patients (TRS-C, n = 37), clozapine-naïve TRS patients (TRS-NC, n = 39), and non-TRS patients (nTRS, n = 35). Clinical symptom severity was assessed using the Positive and Negative Symptom Scale (PANSS), while cognitive function was evaluated using the MATRICS Consensus Cognitive Battery (MCCB). RESULT: The levels of all four glutamate receptor antibodies in TRS-NC were significantly higher than those in nTRS (p < 0.001) and in TRS-C (p < 0.001), and the antibody levels in TRS-C were comparable to those in nTRS. However, no significant associations were observed between antibody levels and symptom severity or cognitive function across all three groups after FDR correction. CONCLUSION: Our findings suggest that TRS may related to increased anti-glutamate receptor antibody levels and provide further evidence that glutamatergic dysfunction and immune processes may contribute to the pathogenesis of TRS. The impact of clozapine on anti-glutamate receptor antibody levels may be a pharmacological mechanism underlying its therapeutic effects.

Establishment of pregnancy-specific lipid reference intervals in pregnant women in a single-centre and assessment of the predictive value of early lipids for gestational diabetes mellitus: a prospective cohort study.

INTRODUCTION: This study was aimed at establishing a pregnancy-specific lipid reference interval (RI) in pregnant women in a single-centre in the Beijing area of China, simultaneously exploring the predictive value of lipid levels in early pregnancy for gestational diabetes mellitus (GDM). MATERIAL AND METHODS: From October 2017 to August 2019, Peking University International Hospital established records for 1588 pregnant women, whose lipid profiles were determined during the first and third trimesters. The Hoffmann technique was used to calculate gestation-specific lipid RI. The 95% reference range for gestational lipids was also estimated for 509 healthy pregnant women screened according to the Clinical and Laboratory Standards Institute guideline. Multivariate logistic regression analysis was used to calculate odds ratios (OR) and their 95% confidence interval (CI), and the receiver operating characteristic (ROC) curve was applied to assess the predictive value of lipids in the first trimester for the diagnosis of GDM. RESULTS: Total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) levels were significantly higher in the third trimester (p < 0.05). Hoffmann technique RI of the lipid profiles and the 95% reference range of the lipid profiles in healthy pregnant women did not differ statistically (p > 0.05). TC, TG, and LDL-C levels were higher in the GDM group in the first trimester (p < 0.05), and the risk of GDM was 2.1 times higher in women with higher TG (95% CI: 1.13-3.77, p < 0.05). The optimal ROC cut-off for TG to predict GDM was 2.375 mmol / L, and the area under the ROC curve was 0.622 (95% CI: 0.592-0.751), with a sensitivity of 73.7% and a specificity of 59.3%. CONCLUSIONS: This study established pregnancy-specific lipid RI for pregnant women in a single centre in the Beijing area of China. Pregnant women with TG ≥ 2.375 mmol/L in the first trimester were at significantly increased risk for GDM.

Canopeo app as image-based phenotyping tool in controlled environment utilizing Arabidopsis mutants.

Canopeo app was developed as a simple, accurate, rapid, and free tool to analyze ground cover fraction (GCF) from red-green-blue (RGB) images and videos captured in the field. With increasing interest in tools for plant phenotyping in controlled environments, the usefulness of Canopeo to identify differences in growth among Arabidopsis thaliana mutants in a controlled environment were explored. A simple imaging system was used to compare Arabidopsis mutants based on the FLAVIN-BINDING, KELCH REPEAT, F-BOX-1 (FKF1) mutation, which has been identified with increased biomass accumulation. Two FKF1 lines such as null expression (fkf1-t) and overexpression (FKF1-OE) lines were used along with wild type (Col-0). Canopeo was used to phenotype plants, based on biomass estimations. Under long-day photoperiod, fkf1-t had increased cellulose biosynthesis, and therefore biomass. Resource partitioning favored seedling vigor and delayed onset of senescence. In contrast, FKF1-OE illustrated a determinative growth habit where plant resources are primarily allocated for seed production. This study demonstrates the use of Canopeo for model plants and highlights its potential for phenotyping broadleaved crops in controlled environments. The value of adapting Canopeo for lab use is those with limited experience and resources have access to phenotyping methodology that is simple, accessible, accurate, and cost-efficient in a controlled environment setting.

Altered spontaneous neurological activity in methamphetamine use disorders and its association with cognitive function.

BACKGROUND: Methamphetamine (MA) is a widely used and detrimental drug, yet the precise mechanisms by which MA affects cognitive function remain unclear. This study aims to investigate the relationship between cognitive function and brain functional imaging in individuals with MA use disorder (MUD). METHODS: This study involved 45 patients diagnosed with MUD and 43 healthy controls (HC). Cognitive function assessment utilized the MATRICS Consensus Cognitive Battery, and functional data were acquired using a 3.0 Tesla magnetic resonance imaging scanner. RESULTS: The MUD group exhibited lower regional homogeneity (ReHo) values in the bilateral postcentral, the left superior temporal, and the left lingual regions compared to the HC group. Additionally, the MUD group displayed higher amplitude of low-frequency fluctuation (ALFF) values in the bilateral fusiform and the left putamen compared to the HC group, along with lower ALFF values in the bilateral postcentral cortices and the left middle cingulate cortex compared to the HC group (all p < 0.05, with false discovery rate corrected). Linear regression analysis revealed a positive correlation between the ReHo value in the right postcentral cortex and the neuropsychology assessment battery-mazes test (p = 0.014). Furthermore, the ALFF value in the left putamen showed negative correlations with the scores of the digit-symbol coding test (p = 0.027), continuous performance test (p = 0.037), and battery-mazes test (p = 0.024). CONCLUSION: Patients with MUD exhibit altered brain spontaneous neurological activities, and the intensity of spontaneous neurological activity in the left putamen is strongly associated with cognitive function.

Relationship between bisphenol A and autoimmune thyroid disease in women of childbearing age.

Background: Autoimmune thyroid disease (AITD) is the main cause of hypothyroidism in women of childbearing age. Bisphenol A (BPA) is an environmental factor affecting AITD. This study aims to investigate relationship between BPA and AITD in women of childbearing age, thereby contributing novel evidence for the prevention of hypothyroidism in this specific demographic. Methods: A total of 155 women of childbearing age were enrolled in this study, including the euthyroid group comprised 60 women with euthyroidism and thyroid autoantibodies negativity and the AITD group consisted of 95 women with euthyroidism and at least one thyroid autoantibody positivity. The general information, thyroid function, thyroid autoantibodies, and thyroid ultrasound results of the two groups of women of childbearing age were recorded. Urinary BPA and urinary BPA/creatinine were detected. The difference of BPA levels between the two groups was compared. logistic regression was used to analyze the correlation between BPA and AITD. Results: The proportion of multiparous and serum thyroid stimulating hormone levels were significantly higher in the AITD group compared to the euthyroid group. Logistic regression analysis revealed that BPA levels did not exhibit a statistically significant association with AITD. Spearman correlation analysis revealed a statistically significant correlation between BPA and urinary iodine levels (r=0.30, P < 0.05), as well as a correlation between urinary BPA and free tetraiodothyronine (FT4) levels (r=0.29, P < 0.05). Conclusion: This study revealed a correlation between urinary BPA levels and FT4 levels. However, it did not establish a relationship between BPA and AITD in women of childbearing age.

Evaluation of the applicability of gasification coarse slag as a fine aggregate in controlled low-strength material: preparation, performance, and environmental effect.

Gasification slag (GS) is rich in SiO2, Al2O3, and Fe2O3, and has excellent particle size gradation, which has the potential to be employed as an aggregate in the field of controlled low-strength material (CLSM). Nevertheless, the large-scale application of GS as the fine aggregate for the preparation of CLSM has been scarcely investigated. In the present work, the applicability of replacing part of coal gangue (CG) with gasification coarse slag (GCS) as fine aggregate for the preparation of CLSM was investigated. The results revealed that using GCS as a fine aggregate improved the flowability of CLSM, and increasing the GCS content from 0 to 50 wt% improved the flowability from 250.0 to 280.0 mm. The 28-day compressive strength of all CLSM conformed to the requirements of ACI Committee 229. Compared to the Blank group, the 7- and 28-day compressive strength of the CLSM increased by 23.07% and 26.80%, respectively, at a GCS content of 50 wt%. The increase in compressive strength was mainly due to the pore-filling and hydration-promoting effect of the GCS, which made the structure denser. The dense structure reduced the expansion rate, absorption, and porosity rate of CLSM and increased the wet density. The optimal process parameter was the addition of 10 wt% of GCS. The results of heavy metal ion leaching showed that the optimal sample GS10 leached all heavy metal ions in much less than the limit values of GB 8978-1996 and GB 5085.3-2007. The results will provide new ideas and technical approaches for the large-scale application of GCS as the fine aggregate in CLSM.

Exploring 3-O-glycosylations of 20(R)-dammarane ginsenosides and the catalytic mechanism underlying the stereoselectivity with the combined assistance of AlphaFold 2 and molecular docking.

Glycosylation at C3-OH is the favorable modification for pharmaceutical activities and diversity expansion of 20(R)-dammarane ginsenosides. The 3-O-glycosylation, exclusively occurring in 20(R)-PPD ginsenosides, has never been achieved in 20(R)-PPT ginsenosides. Herein, 3-O-glycosylation of 20(R)-PPT enabled by a glycosyltransferase (GT) OsSGT2 was achieved with the combined assistance of AlphaFold 2 and molecular docking. Firstly, we combined AlphaFold2 algorithm and molecular docking to predict interactions between 20(R)-PPT and candidate GTs. A catalytically favorable binding geometry was thus identified in the OsSGT2-20(R)-PPT complex, suggesting OsSGT2 might act on 20(R)-PPT. The enzymatic assays demonstrated that OsSGT2 reacted with varied sugar donors to form 20(R)-PPT 3-O-glycosides, exhibiting donor promiscuity. Additionally, OsSGT2 displayed acceptor promiscuity, catalyzing 3-O-glucosylation of 20(R/S)-PPT, 20(R/S)-PPD and 20(R/S)-Rh1, respectively. Protein engineering on OsSGT2 was thus performed to probe its catalytic mechanism underlying its stereoselectivity. The W207A mutant preferred 20(S)-dammarane aglycons, while F395Q/A396G(QG) displayed a conversion enhancement towards both 20(R/S)-dammarane aglycons. The QG mutant was then used to synthesize 20(R)-PPT 3-O-glucoside, which displayed a moderate angiotensin-converting enzyme inhibitory effect with an IC50 of 27.5 ± 4.7 µM, superior to that of its 20(S)-epimer, with the combined assistance of target fishing and reverse docking. The water solubility of 20(R)-PPT 3-O-glucoside increased as well.

Free triiodothyronine (FT3)-to-free thyroxine (FT4) ratio identified as a risk factor for gestational diabetes in euthyroid pregnant women: insights from a Chinese population cohort study.

Background: To explore the association between thyroid hormones and gestational diabetes mellitus in euthyroid pregnant women, with the aim of preventing the occurrence of gestational diabetes mellitus. Methods: In this prospective study, a total of 1222 euthyroid pregnant women in their first trimester were recruited at Peking University International Hospital between December 2017 and March 2019. These participants underwent an oral glucose tolerance test during the 24-28 weeks of gestation. Results: During early pregnancy, the gestational diabetes mellitus group displayed lower levels of free thyroxine when compared to the non-gestational diabetes mellitus group. Additionally, the ratio of free triiodothyronine to free thyroxine in the gestational diabetes mellitus group during early pregnancy was significantly higher (p<0.05). The ratio of free triiodothyronine to free thyroxine during early pregnancy showed a positive correlation with blood glucose levels at 0, 60, and 120 min both before and after glucose loading (all p<0.05). During early pregnancy, there was a negative relationship between free thyroxine levels and fasting blood glucose. The free triiodothyronine levels were positively correlated to blood glucose levels at 120 min following glucose loading (all p<0.05). Conclusion: The ratio of free triiodothyronine-to-free thyroxine is an independent risk factor for gestational diabetes mellitus and has the potential to be a predictor for gestational diabetes mellitus in euthyroid pregnant women.

USBDAN: Unsupervised Scale-aware and Boundary-aware Domain Adaptive Network for Gastric Tumor Segmentation.

Accurate segmentation of gastric tumors from computed tomography (CT) images provides useful image information for guiding the diagnosis and treatment of gastric cancer. Researchers typically collect datasets from multiple medical centers to increase sample size and representation, but this raises the issue of data heterogeneity. To this end, we propose a new cross-center 3D tumor segmentation method named unsupervised scale-aware and boundary-aware domain adaptive network (USBDAN), which includes a new 3D neural network that efficiently bridges an Anisotropic neural network and a Transformer (AsTr) for extracting multi-scale features from the CT images with anisotropic resolution, and a scale-aware and boundary-aware domain alignment (SaBaDA) module for adaptively aligning multi-scale features between two domains and enhancing tumor boundary drawing based on location-related information drawn from each sample across all domains. We evaluate the proposed method on an in-house CT image dataset collected from four medical centers. Our results demonstrate that the proposed method outperforms several state-of-the-art methods.

How to determine the optimal proximal fusion level for Scheuermann kyphosis.

OBJECTIVE: To determine optimal proximal fusion levels for instrumented spinal fusion for Scheuermann kyphosis. METHODS: We reviewed 86 patients (33 women) who underwent corrective instrumented spinal fusion for Scheuermann kyphosis. All patients had long-cassette upright lateral radiographs taken preoperatively, postoperatively, and at 2 years and the last follow-up. Demographic, radiographic, and surgical parameters were compared between patients with and without PJK. RESULTS: PJK occurred in 28 patients (32%). The mean maximum Cobb angle was 85.8° ± 11.7° preoperatively, 54.8° ± 14.2° postoperatively, and 59.7° ± 16.8° at the last follow-up. Age and sex did not differ between the PJK and non-PJK groups (P > 0.05). The preoperative curve characteristics, fusion levels, and corrective ratio were similar in both groups (P > 0.05). The maximal Cobb angle at 2 years and the last follow-up significantly differed between the 2 groups (P < 0.05). The proportion of patients with the uppermost instrumented vertebra (UIV) at or above the proximal end vertebra (PEV) was similar in both groups (P > 0.05). The proportion of patients with UIV at or above T2 was significantly greater in the non-PJK group (P < 0.05). PJK was significantly associated with a C7 plumb line (C7PL)-sacrum distance ≥ 50 mm (P < 0.05). CONCLUSION: PJK is the main cause of postoperative correction loss. Proper fusion-level selection can reduce PJK occurrence. We recommend having the UIV at T2 or above, especially when the C7PL-sacrum distance ≥ 50 mm.

Optimization of ultrasonic-assisted extraction of flavonoids from Lactuca indica L. cv. Mengzao and their antioxidant properties.

In this study, the ultrasound-assisted extraction (UAE) conditions of flavonoids from Lactuca indica L.cv. Mengzao (LIM) leaves was optimized, and the flavonoids content and their antioxidant potential in different parts were analyzed. The optimal extraction parameters to obtain the highest total flavonoids content (TFC) were a a ratio of liquid to solid of 24.76 mL/g, ultrasonic power of 411.43 W, ethanol concentration of 58.86% and an extraction time of 30 min, the average TFC of LIM leaves could reach 48.01 mg/g. For the yield of flavonoids, the UAE method had the best extraction capacity compared with solvent extraction and microwave-assisted extraction (MAE). In general, the TFC in different parts of LIM followed the order flower > leaf > stem > root, the flowering period is the most suitable harvesting period. From ultra-high performance liquid chromatography-mass spectrometry (UPLC-MS) quantification, the flower samples showed significantly higher six flavonoids and had the highest radical scavenging capacities compared to other samples. A high positive correlation was observed between the antioxidant activity and TFC, luteolin-7-O-glucoside and rutin were significantly (p < 0.05) correlated with all antioxidant evaluations. This study provides valuable information for the development and utilization of flavonoids in Lactuca indica as ingredients in food, feed and nutritional health products.

Tracking the Progression of the Simulated Bronze Disease-A Laboratory X-ray Microtomography Study.

The internal three-dimensional characteristics of X-ray microtomography (micro-CT) has great application potential in the field of bronze corrosion. This work presents a method of simulating bronze disease based on an in situ micro-CT image to study the characteristics of the oxidative hydrolysis reactions of copper(I) chloride and copper(II) chloride dihydrate. A series of high-resolution reconstruction images were obtained by carrying out micro-CT at three key points throughout the experiment. We found that the reactions of copper(I) chloride and copper(II) chloride dihydrate showed different characteristics at different stages of the simulation in the micro-CT view. The method proposed in this work specifically simulated one single type of bronze corrosion and characterized the evolution characteristics of simulated bronze disease. It provides a new perspective to investigate bronze disease and can help improve the subsequent use of micro-CT to distinguish real bronze corrosions.

[A new dihydrochalcone from Humulus scandens].

To study the chemical constituents from the stems and leaves of Humulus scandens, this study isolated thirteen compounds by different chromatographic methods including silica gel column, ODS, Sephadex LH-20 and preparative HPLC. Based on comprehensive analysis, the chemical structures were elucidated and identified as citrunohin A(1), chrysosplenetin(2), casticin(3), neoechinulin A(4), ethyl 1H-indole-3-carboxylate(5), 3-hydroxyacetyl-indole(6),(1H-indol-3-yl) oxoacetamide(7), inonotusic acid(8), arteannuin B(9), xanthotoxol(10), α-tocopherol quinone(11), eicosanyl-trans-p-coumarate(12), and 9-oxo-(10E,12E)-octadecadienoic acid(13). Among them, compound 1 was a new dihydrochalcone, and the other compounds were obtained from H. scandens for the first time.

Optical noise-resistant nonreciprocal phonon blockade in a spinning optomechanical resonator.

A scheme of nonreciprocal conventional phonon blockade (PB) is proposed in a spinning optomechanical resonator coupled with a two-level atom. The coherent coupling between the atom and breathing mode is mediated by the optical mode with a large detuning. Due to the Fizeau shift caused by the spinning resonator, the PB can be implemented in a nonreciprocal way. Specifically, when the spinning resonator is driven from one direction, the single-phonon (1PB) and two-phonon blockade (2PB) can be achieved by adjusting both the amplitude and frequency of the mechanical drive field, while phonon-induced tunneling (PIT) occurs when the spinning resonator is driven from the opposite direction. The PB effects are insensitive to cavity decay because of the adiabatic elimination of the optical mode, thus making the scheme more robust to the optical noise and still feasible even in a low-Q cavity. Our scheme provides a flexible method for engineering a unidirectional phonon source with external control, which is expected to be used as a chiral quantum device in quantum computing networks.

Sex differences in the association of treatment-resistant schizophrenia and serum interleukin-6 levels.

BACKGROUND: Low-grade inflammation and altered inflammatory markers have been observed in treatment-resistant schizophrenia (TRS). Interleukin-6 (IL-6) is one of the pro-inflammatory cytokines linked with TRS and receives increasing attention. Previous studies showed that patients with TRS might have higher IL-6 levels compared with healthy individuals and treatment-responsive patients. Besides, emerging evidence has suggested that there are sex differences in the associations between IL-6 levels and various illnesses, including chronic hepatitis C, metabolic syndrome, etc.; however, there is limited study on TRS. In this present study, we aimed to compare the serum IL-6 levels of TRS and partially responsive schizophrenia (PRS) and explore potential sex differences in the association of TRS and IL-6 levels. METHODS: The study population consisted of a total of 90 patients with schizophrenia: 64 TRS patients (45.3% males and 54.7% females) and 26 PRS patients (46.2% males and 53.8% females). We measured serum IL-6 levels using enzyme-linked immunosorbent assay (ELISA) and analyzed them separately by gender, controlling for confounders (age, education, medication, body mass index, and PANSS scores) rigorously. RESULT: The results showed that patients with TRS had higher serum IL-6 levels than patients with PRS (p = 0.002). In females, IL-6 levels increased significantly in the TRS group compared with the PRS group (p = 0.005). And a positive correlation tendency was observed between IL-6 levels and PANSS general sub-scores (r = 0.31, p = 0.039), although this correlation was not significant after correcting for multiple comparisons. Whereas, there were no differences in IL-6 levels between the TRS and PRS (p = 0.124) in males. CONCLUSION: Our findings provided evidence supporting the hypothesis that the inflammatory response system (IRS) may play a role in the pathogenesis of TRS in a sex-dependent manner. In addition, sex differences in the immune dysfunction of individuals with schizophrenia cannot be neglected, and inflammation in male and female TRS should be discussed separately.

Relationship between the Central and Peripheral Thyroid Sensitivity Indices and Fetal Macrosomia: A Cohort Study of Euthyroid Pregnant Women in China.

(1) Background: To explore the correlation between central and peripheral thyroid sensitivity indices and macrosomia in euthyroid pregnant women and to provide clinical basis for the prevention and treatment of macrosomia. (2) Methods: This study is a prospective study. A total of 1176 euthyroid women in early pregnancy in the obstetrics department of Peking University International Hospital from December 2017 to March 2019 were enrolled. The women were divided into two groups, namely the macrosomia and non-macrosomia groups, according to birth weight. (3) Results: The level of free triiodothyronine (FT3), thyroid-stimulating hormone (TSH), thyroid feedback quantile-based index (TFQI), thyrotropin-T4 resistance index (TT4RI), thyroid-stimulating hormone index (TSHI), and free triiodothyronine/free thyroxine (FT3/FT4) in the macrosomia group was higher than that in the non-macrosomia group (p < 0.05). The multivariate logistic regression model showed that FT3, TFQI, TT4RI, TSHI, and FT3/FT4 were independent risk factors for macrosomia in early pregnancy after adjusting for age, body mass index, parity, blood pressure, blood glucose, and blood lipid levels (p < 0.05, respectively). (4) Conclusions: TFQI, TT4RI, TSHI, and FT3/FT4 are independent risk factors for fetal macrosomia in early pregnancy in euthyroid women.

Suicidal ideation in Chinese patients with chronic schizophrenia: prevalence, clinical correlates, and relationship with alexithymia.

Suicidal ideation (SI) is common among people with schizophrenia. However, it has received less attention than suicide attempts (SA), especially in the Chinese population. Alexithymia is a well-established risk factor for SI across different populations. Nevertheless, very few studies evaluated their relationship in schizophrenia patients. We aimed to determine the prevalence and clinical correlates of SI and its relationship with alexithymia in 812 Chinese chronic schizophrenia inpatients. We assessed SI, clinical symptoms, and alexithymia by the Beck Scale for Suicidal Ideation, the Positive and Negative Syndrome Scale (PANSS), and the Toronto Alexithymia Scale, respectively. A multiple logistic regression model was conducted to identify independent correlates of SI. Receiver operating characteristic (ROC) curves and area under the curve (AUC) were performed to determine the ability of our model to distinguish between patients with and without SI. 10% (n = 84) reported current SI. Lifetime SA (OR, 4.68; 95% CI 2.76-7.94, p < 0.001), PANSS depressive factor (OR, 1.24; 95% CI 1.12-1.38, p < 0.001), PANSS positive subscale (OR, 1.055; 95% CI 1.004-1.108, p = 0.035), and difficulty identifying emotions (OR, 1.07; 95% CI 1.03-1.12, p = 0.002) were associated with SI. The AUC value was 0.80, indicating excellent distinguishing capabilities. Timely assessments of these factors may help identify schizophrenia patients who are at risk for SI.

A pilot pharmacogenetic study of calcium channel blocker treatment of bipolar mania.

Common genetic variants located in calcium channel genes are important markers of genetic susceptibility for bipolar disorder (BD). Previous clinical trials with Calcium Channel Blocker (CCB) medication improved mood stability for some BD patients. We hypothesize that manic patients who carried calcium channel risk variants would differentially benefit from treatment with CCBs. In this pilot study, 50 BD patients (Chinese: 39; US: 11) who were hospitalized for manic episodes were given add-on CCB treatment. We determined genotypes for each patient. There was a significant decrease in the Young Mania Rating Scale (YMRS) after add-on medication treatment. Of note, two intronic variants of the Calcium Voltage-Gated Channel Subunit Alpha1 B (CACNA1B) were associated with treatment outcomes for manic patients: rs2739258 and rs2739260. BD rs2739258/rs2739260 AG-allele carriers had a better treatment response with add-on CCB than those carrying the AA or GG genotypes by survival analysis. Although these findings did not pass multiple testing correction, this study suggests that single-nucleotide polymorphisms (SNPs) residing in calcium channel genes could be predictors for response to add-on CCB treatment of bipolar mania patients, and that calcium channel genes may be involved in treatment responses for BD.

Clinical and genetic features of Kenny-Caffey syndrome type 2 with multiple electrolyte disturbances: A case report.

BACKGROUND: Hypoparathyroidism, which can be sporadic or a component of an inherited syndrome, is the most common cause of hypocalcemia. If hypocalcemia is accompanied by other electrolyte disturbances, such as hypokalemia and hypomagnesemia, then the cause, such as renal tubular disease, should be carefully identified. CASE SUMMARY: An 18-year-old female visited our clinic because of short stature and facial deformities, including typical phenotypes, such as low ear position, depression of the nasal bridge, small hands and feet, and loss of dentition. The lab results suggested normal parathyroid hormone but hypocalcemia. In addition, multiple electrolyte disturbances were found, including hypokalemia, hypocalcemia and hypomagnesemia. The physical signs showed a short fourth metatarsal bone of both feet. The X-ray images showed cortical thickening of long bones and narrowing of the medulla of the lumen. Cranial computed tomography indicated calcification in the bilateral basal ganglia. Finally, the genetic investigation showed a de novo heterogenous mutation of "FAM111A" (c. G1706A:p.R569H). Through a review of previously reported cases, the mutation was found to be the most common mutation site in Kenny-Caffey syndrome type 2 (KCS2) cases reported thus far (16/23, 69.6%). The mutation was slightly more prevalent in females than in males (11/16, 68.8%). Except for hypocalcemia, other clinical manifestations are heterogeneous. CONCLUSION: As a rare autosomal dominant genetic disease of hypoparathyroidism, the clinical manifestations of KCS2 are atypical and diverse. This girl presented with short stature, facial deformities and skeletal deformities. The laboratory results revealed hypocalcemia as the main electrolyte disturbance. Even though her family members showed normal phenotypes, gene detection was performed to find the mutation of the FAM111A gene and confirmed the diagnosis of KCS2.

A Study Against Colon Cancer Mechanism of Xanthium Sibiricum Herba Based on Computer Simulation and Bioinformatics.

INTRODUCTION: Cancer is one of the leading causes of death worldwide, accounting for nearly one in six deaths in 2020. As a folk medicine, Xanthium sibiricum Herba (XSH) has been used many times in clinical practice for the treatment of various diseases. With the increasing number of cancer patients, there is a clinical need to find effective anti-cancer drugs. AIM: This study aims to explores the bioactivity and the anti-cancer mechanism of XSH. METHODS: In this study, bioinformatics, network pharmacology, molecular docking, molecular dynamics simulation techniques, and apoptosis assay were used to explore the bioactivity and the anti-cancer mechanism of XSH. RESULTS: Finally, seven active ingredients in XSH after the screening were obtained, the two most active compounds were ß-sitosterol and aloe-emodin, and good anti-cancer activity of XSH was predicted. DISCUSSION: Four core targets were obtained from the PPI network map, namely Caspase-3 (CASP3), Transcription factor AP-1 (JUN), Myc proto-oncogene protein (MYC), and cellular tumor antigen p53 (TP53). GO and KEGG analyses showed that the mechanism of XSH anti-cancer is mainly related to the apoptosis process, and the main signaling pathways are enriched in the p53 signaling pathway, Apoptosis, and MAPK signaling. The molecular docking and molecular dynamics simulation results showed that CASP3, JUN, MYC, and TP53 had a high affinity with ß-sitosterol and aloe-emodin. Bioinformatics analyses demonstrated the importance of core targets. Apoptosis assay showed that XSH could significantly promote the apoptosis of cancer cells, and inhibit their proliferation and migration, especially colon cancer cells. CONCLUSION: This study uncovered the main active components, bioactivities, and potential targets of XSH, and further revealed the multi-component, multi-target, and multi-pathway mechanism of XSH for cancer treatment and promoting apoptosis.