The potential value of oral microbial signatures for prediction of oral squamous cell carcinoma based on machine learning algorithms.

OBJECTIVE: This study aimed to explore the potential predictive value of oral microbial signatures for oral squamous cell carcinoma (OSCC) risk based on machine learning algorithms. METHODS: The oral microbiome signatures were assessed in the unstimulated saliva samples of 80 OSCC patients and 179 healthy individuals using 16S rRNA gene sequencing. Four different machine learning classifiers were used to develop prediction models. RESULTS: Compared with control participants, OSCC patients had a higher microbial dysbiosis index (MDI, p < 0.001). Among four machine learning classifiers, random forest (RF) provided the best predictive performance, followed by the support vector machines, artificial neural networks and naive Bayes. After controlling the potential confounders using propensity score matching, the optimal RF model was further developed incorporating a minimal set of 20 bacteria genera, exhibiting better predictive performance than the MDI (AUC: 0.992 vs. 0.775, p < 0.001). CONCLUSIONS: The novel MDI and RF model developed in this study based on oral microbiome signatures may serve as noninvasive tools for predicting OSCC risk.

A sleep staging model on wavelet-based adaptive spectrogram reconstruction and light weight CNN.

Effective methods for automatic sleep staging are important for diagnosis and treatment of sleep disorders. EEG has weak signal properties and complex frequency components during the transition of sleep stages. Wavelet-based adaptive spectrogram reconstruction (WASR) by seed growth is utilized to capture dominant time-frequency patterns of sleep EEG. We introduced variant energy from Teager operator in WASR to capture hidden dynamic patterns of EEG, which produced additional spectrograms. These spectrograms enabled a light weight CNN to detect and extract finer details of different sleep stages, which improved the feature representation of EEG. With specially designed depthwise separable convolution, the light weight CNN achieved more robust sleep stage classification. Experimental results on Sleep-EDF 20 dataset showed that our proposed model yielded overall accuracy of 87.6%, F1-score of 82.1%, and Cohen kappa of 0.83, which is competitive compared with baselines with reduced computation cost.

Kinect-based objective assessment of the acute levodopa challenge test in parkinsonism: a feasibility study.

INTRODUCTION: The acute levodopa challenge test (ALCT) is an important and valuable examination but there are still some shortcomings with it. We aimed to objectively assess ALCT based on a depth camera and filter out the best indicators. METHODS: Fifty-nine individuals with parkinsonism completed ALCT and the improvement rate (IR, which indicates the change in value before and after levodopa administration) of the Movement Disorder Society-Sponsored Revision of the Unified Parkinson's Disease Rating Scale part III (MDS-UPDRS III) was calculated. The kinematic features of the patients' movements in both the OFF and ON states were collected with an Azure Kinect depth camera. RESULTS: The IR of MDS-UPDRS III was significantly correlated with the IRs of many kinematic features for arising from a chair, pronation-supination movements of the hand, finger tapping, toe tapping, leg agility, and gait (rs = - 0.277 ~ - 0.672, P < 0.05). Moderate to high discriminative values were found in the selected features in identifying a clinically significant response to levodopa with sensitivity, specificity, and area under the curve (AUC) in the range of 50-100%, 47.22%-97.22%, and 0.673-0.915, respectively. The resulting classifier combining kinematic features of toe tapping showed an excellent performance with an AUC of 0.966 (95% CI = 0.922-1.000, P < 0.001). The optimal cut-off value was 21.24% with sensitivity and specificity of 94.44% and 87.18%, respectively. CONCLUSION: This study demonstrated the feasibility of measuring the effect of levodopa and objectively assessing ALCT based on kinematic data derived from an Azure Kinect-based system.

The natural course of idiopathic cervical dystonia.

Idiopathic cervical dystonia (ICD) is by far the largest subgroup of dystonia. Still, its natural course is largely unknown. We studied the natural course of 100 ICD patients from our botulinum toxin clinics (age at ICD onset 45.8 ± 13.5 years, female/male ratio 2.0) over a period of 17.5 ± 11.5 years with follow-ups during botulinum toxin therapy and with semi-structured interviews. Two courses of ICD could be distinguished by symptom development of more or less than 6 months. ICD-type 2 was less frequent (19% vs 81%, p < 0.001), had a more rapid onset (8.7 ± 8.0 weeks vs 3.8 ± 3.5 years), a higher remission rate (92% vs 5%, p < 0.001) and a higher prevalence of excessive psychological stress preceding ICD (63% vs 1%, p < 0.001). In both ICD-types, the plateau phase was non-progressive. Significant differences in patient age at ICD onset, latency and extent of remission, female/male ratio and prevalence of family history of dystonia could not be detected. ICD is a non-progressive disorder. ICD-type 1 represents the standard course. ICD-type 2 features rapid onset, preceding excessive psychological stress and a high remission rate. These findings will improve prognosis, treatment strategies and understanding of underlying disease mechanisms. They contradict the widespread fear of patients of a constant and continued decline of their condition. Excessive psychological stress may be an epigenetic factor triggering the manifestation of genetically predetermined dystonia.

Excessive psychological stress preceding the onset of idiopathic cervical dystonia.

Idiopathic cervical dystonia (ICD) is the largest subgroup of dystonia. Psychological stress as a triggering factor has long been discussed, but detailed descriptions are lacking. We report on a group of 13 patients with ICD and preceding excessive psychological stress (age at ICD onset 39.0 ± 13.9 years, 7 females, 6 males). The observation period was 7.8 ± 5.0 years. Excessive psychological stress included partner conflicts (divorce and separation, domestic violence), special familial burdens, legal disputes and migration. It started 8.3 ± 3.9 months before ICD onset. In 85% of our patients (typical cases), ICD developed within 5.8 ± 4.4 weeks, then lasted 18.5 ± 8.3 months, before it started to remit 2.7 ± 0.8 years after its onset to 54.5 ± 35.3% of its maximal severity. Idiopathic dystonia is thought to be based upon a genetic predisposition triggered by epigenetic factors. Our study suggests that excessive psychological stress could be one of them. Pathophysiologic elements are only vaguely identified, but could include the endoplasmic reticulum stress response, cerebellar 5HT-2A receptors and the metabolism of heat shock proteins. Whilst the clinical presentation of ICD preceded by excessive psychological stress is typical, its course is atypical with rapid onset and fast and substantial remission.

Early-onset and late-onset Parkinson's disease exhibit a different profile of gait and posture features based on the Kinect.

INTRODUCTION: Gait and posture abnormalities are the common disabling motor symptoms in Parkinson's disease (PD). This study aims to investigate the differential characteristics of gait and posture in early-onset PD (EOPD) and late-onset PD (LOPD) using the Kinect depth camera. METHODS: Eighty-eight participants, including two subgroups of 22 PD patients and two subgroups of 22 healthy controls (HC) matched for age, sex, and height, were enrolled. Gait and posture features were quantitatively assessed using a Kinect-based system. A two-way analysis of variance was used to compare the difference between different subgroups. RESULTS: EOPD had a significantly higher Gait score than LOPD (p = 0.031). Specifically, decreased swing phase (p = 0.034) was observed in the EOPD group. Although the Posture score was similar between the two groups, LOPD was characterized by an increased forward flexion angle of the trunk at the thorax (p = 0.042) and a decreased forward flexion angle of the head relative to the trunk (p = 0.009). Additionally, age-independent features were observed in both PD subgroups, and post hoc tests revealed that EOPD generally performed worse gait features. In comparison, LOPD was characterized by worse performance in posture features. CONCLUSIONS: EOPD and LOPD exhibit different profiles of gait and posture features. The phenotype-specific characteristics likely reflect the distinct neurodegenerative processes between them.

Kinect-based objective evaluation of bradykinesia in patients with Parkinson's disease.

Objective: To quantify bradykinesia in Parkinson's disease (PD) with a Kinect depth camera-based motion analysis system and to compare PD and healthy control (HC) subjects. Methods: Fifty PD patients and twenty-five HCs were recruited. The Movement Disorder Society-Sponsored Revision of the Unified Parkinson's Disease Rating Scale part III (MDS-UPDRS III) was used to evaluate the motor symptoms of PD. Kinematic features of five bradykinesia-related motor tasks were collected using Kinect depth camera. Then, kinematic features were correlated with the clinical scales and compared between groups. Results: Significant correlations were found between kinematic features and clinical scales (P < 0.05). Compared with HCs, PD patients exhibited a significant decrease in the frequency of finger tapping (P < 0.001), hand movement (P < 0.001), hand pronation-supination movements (P = 0.005), and leg agility (P = 0.003). Meanwhile, PD patients had a significant decrease in the speed of hand movements (P = 0.003) and toe tapping (P < 0.001) compared with HCs. Several kinematic features exhibited potential diagnostic value in distinguishing PD from HCs with area under the curve (AUC) ranging from 0.684-0.894 (P < 0.05). Furthermore, the combination of motor tasks exhibited the best diagnostic value with the highest AUC of 0.955 (95% CI = 0.913-0.997, P < 0.001). Conclusion: The Kinect-based motion analysis system can be applied to evaluate bradykinesia in PD. Kinematic features can be used to differentiate PD patients from HCs and combining kinematic features from different motor tasks can significantly improve the diagnostic value.

DNMT3b affects colorectal cancer development by regulating FLI1 through DNA hypermethylation.

Friend leukemia integration 1 (FLI1) is an ETS transcription factor family member. Here, we identified cg11017065 as the most hyper-methylated cytosine and guanine (CpG) in colorectal cancer (CRC), which belongs to the FLI1 gene. Moreover, integrated bioinformatics prediction and analysis of our cohort showed that FLI1 expression was downregulated and DNA methylation was elevated in CRC. Bioinformatics prediction also indicated that patients overexpressing FLI1 had higher survival rates than those with low FLI1 expression. CRC cells with ectopic expression of FLI1 had reduced invasion, migration, cloning ability and increased apoptosis. Furthermore, DNA-methyltransferase 3b (DNMT3b) was found to be significantly overexpressed in CRC, and low DNMT3b expression predicted a prolonged survival. DNMT3b bound to the FLI1 promoter. Inhibition of DNMT3b increased FLI1 expression and inhibited the malignant phenotype of CRC cells. Inhibition of FLI1 reversed the phenotypic modulation by DNMT3b depletion in vitro and in vivo. In conclusion, our data indicate that DNMT3b potentiates CRC cell proliferation, migration, and invasion through downregulating FLI1.

Genetic spectrum and clinical features in a cohort of Chinese patients with isolated dystonia.

Dystonia is a genetically and phenotypically heterogeneous disorder that occurs in isolation (isolated dystonia) or in combination with other movement disorders. To determine the genetic spectrum in isolated dystonia, we enrolled 88 patients with isolated dystonia for whole-exome sequencing (WES). Seventeen mutations, including nine novel ones, were identified in 19 of the 88 patients, providing a 21.59% positive molecular diagnostic rate. Eleven distinct genes were involved, of which TOR1A and THAP1 accounted for 47.37% (9/19) of the positive cases. A novel missense variant, p.S225R in TOR1A, was found in a patient with adolescence-onset generalized dystonia. Cellular experiments revealed that p.S255R results in the abnormal aggregation of Torsin-1A encoding by TOR1A. In addition, we reviewed the clinical and genetic features of the isolated dystonia patients carrying TOR1A, THAP1, ANO3, and GNAL mutations in the Chinese population. Our results expand the genetic spectrum and clinical profiles of patients with isolated dystonia and demonstrate WES as an effective strategy for the molecular diagnosis of isolated dystonia.

How to Avoid Misdiagnosing Spontaneous Cervical Spinal Epidural Hematoma as Ischemic Stroke: 3 Case Reports and Literature Review.

When spontaneous cervical spinal epidural hematoma (SCEH) presents with hemiparesis, it can be misdiagnosed with ischemic stroke (IS), and the treatment of IS such as thrombolysis may deteriorate the symptoms of patients with SCEH, leading to worse sequelae or even death. We reported 3 SCEH patients who were initially suspected as IS in our center between Jun 2020 and April 2022 and analyzed their clinical characteristics together with 48 patients reported in the literature from Jan 1995 to April 2022. Two of the 3 SCEH patients had neck symptoms, while none of them presented cranial nerve symptoms. Cranial computed tomography (CT) scans were negative; however, abnormal signals in the cervical spinal canal were observed during cranial computed tomography angiography (CTA) and subsequent cervical CT confirmed the diagnosis of SCEH. All of them avoid mistreatment with recombinant tissue plasminogen activator (rt-PA). Subsequently, we analyzed the clinical characteristics of a total of 51 patients. Thirteen of them developed symptoms during activity. Neck pain was an important sign of SCEH because 35 patients had neck pain or neck discomfort. Sensory impairment was reported in a small proportion of patients (11/51), which varied a lot in the patients. Some special manifestations highly suggested spinal cord lesions and provided evidence for the early differential diagnosis of SCEH and stroke, but the incidence of which was quite low: ipsilateral Horner syndrome in 2 patients, Brown-Séquard syndrome in 2 cases, and Lhermitte's sign in 1 case. Only a minority (8/51) of the patients were correctly diagnosed at the emergency unit using cervical CT. Six patients were correctly diagnosed when performing CTA. A large portion of the cases (21/51) were first misdiagnosed as IS, but no responsible lesions were found on cranial magnetic resonance imaging (MRI), and subsequent cervical MRI confirmed the diagnosis. Sixteen patients were diagnosed with SCEH after the deterioration of symptoms. A total of 13 patients received rt-PA, and 10 of them had symptoms aggravation after thrombolysis. For patients with acute onset of hemiparesis but without cranial nerve symptoms, especially those accompanied by clinical features such as neck pain, ipsilateral Horner syndrome, Brown-Séquard syndrome, and Lhermitte's sign, SCEH should be highly suspected rather than stroke. Careful differential diagnosis should be performed with a comprehensive medical history and thorough physical examination. Cervical CT scan is a reasonable choice for quick differential diagnosis prior to administering potentially harmful therapy, especially rt-PA.

Exosomal hsa_circRNA_047733 integrated with clinical features for preoperative prediction of lymph node metastasis risk in oral squamous cell carcinoma.

BACKGROUND: To evaluate whether exosomal circRNAs could serve as diagnostic biomarkers for the accurate preoperative prediction of lymph node metastasis (LNM) risk in oral squamous cell carcinoma (OSCC) patients. METHODS: A combinative strategy of exosomal circRNAs microarray and qRT-PCR verification was employed to dig LNM-related circRNA signatures. Then, a dynamic nomogram was developed based on candidate circRNAs and preoperative clinical features and the calibration, discrimination, and clinical use of the nomogram were evaluated. RESULTS: According to the microarray, three circRNAs derived from the tumor were associated with preoperative LNM risk, including hsa_circRNA_047733, hsa_circRNA_024144 and hsa_circRNA_403472. The hsa_circRNA_047733 was further verified to be significantly downregulated in patients with LNM (+) as compared with those with LNM (-) (p = 0.007). Patients with the higher expression of hsa_circRNA_047733 showed a lower risk of LNM (multivariate-adjusted OR = 0.22, 95%CI: 0.06-0.83). The bioinformatics prediction showed that hsa_circRNA_047733 might sponge miR-4464/miR-4748 to regulate RPS21 expression. A dynamic nomogram integrating exosomal hsa_circRNA_047733 with five clinicopathological characteristics (tumor site, leukocyte level, maximum tumor diameter, and LNM reported by MRI and preoperative biopsy differentiation) was developed. The model displayed an excellent discrimination ability (AUC = 0.868, 95%CI: 0.781-0.955) and great calibration. The decision curve revealed a higher net benefit superior to the baseline model at an 80% threshold probability. CONCLUSION: The data provide preliminary evidence that exosomal hsa_circRNA_047733 might be a novel biomarker for the LNM of OSCC. The hsa_circRNA_047733-based dynamic nomogram could serve as a convenient preoperative assessment tool to predict the risk of LNM for OSCC patients.

[Analysis of IVD gene variants in four children with isovalerate acidemia].

OBJECTIVE: To detect variants of IVD gene among 4 neonates with suspected isovalerate acidemia in order to provide a guidance for clinical treatment. METHODS: 111 986 newborns and 7461 hospitalized children with suspected metabolic disorders were screened for acyl carnitine by tandem mass spectrometry. Those showing a significant increase in serum isovaleryl carnitine (C5) were analyzed for urinary organic acid and variants of the IVD gene. RESULTS: Four cases of isovalerate acidemia were detected, which included 2 asymptomatic newborns (0.018‰, 2/111 986) and 2 children suspected for metabolic genetic diseases (0.268‰, 2/7461). The formers had no obvious clinical symptoms. Analysis of acyl carnitine has suggested a significant increase in C5, and urinary organic acid analysis has shown an increase in isovaleryl glycine and 3-hydroxyisovalerate. Laboratory tests of the two hospitalized children revealed high blood ammonia, hyperglycemia, decreased red blood cells, white blood cells, platelets and metabolic acidosis. The main clinical manifestations have included sweaty foot-like odor, feeding difficulty, confusion, drowsiness, and coma. Eight variants (5 types) were detected, which included c.158G>A (p.Arg53His), c.214G>A (p.Asp72Asn), c.548C>T (p.Ala183Val), c.757A>G (p.Thr253Ala) and 1208A>G (p.Tyr403Cys). Among these, c.548C>T and c.757A>G were unreported previously. None of the variants was detected by next generation sequencing of 2095 healthy newborns, and all variants were predicted to be likely pathogenic based on the guidelines from the American College of Medical Genetics and Genomics. CONCLUSION: The incidence of isovalerate acidemia in Liuzhou area is quite high. Screening of metabolic genetic diseases is therefore recommended for newborns with abnormal metabolism. The discovery of novel variants has enriched the mutational spectrum of the IVD gene.

Tumor-augmenting Effect of Histone Methyltransferase WHSC1 on Colorectal Cancer Via Epigenetic Upregulation of TACC3 and PI3K/Akt Activation.

BACKGROUND: Wolf-Hirschhorn syndrome candidate 1 (WHSC1) is a histone methyltransferase which is frequently expressed in an aberrant manner in tumors, but its specific roles and targets in colorectal cancer (CRC) remain unclear. METHODS: Expression of WHSC1 in CRC tissues and cells was examined by RT-qPCR, immunohistochemistry and immunoblot assays. WHSC1 was knocked down in CRC cells to examine its effect on cell proliferation, invasiveness, migration, epithelial-mesenchymal transition (EMT) activity and apoptosis. The binding between WHSC1 and transforming acidic coiled-coil containing protein 3 (TACC3) was predicted using bioinformatics systems and subsequently validated. In addition, altered expression of TACC3 was introduced into CRC cells to perform functional assays. Stably transfected cells were injected into nude mice to induce xenograft tumors. RESULTS: WHSC1 was highly expressed in CRC tumor tissues and cells with a positive correlation with TACC3 concentration. Specific downregulation of WHSC1 in two CRC cell lines blocked cell proliferation, invasiveness, EMT and migration activity and promoted cell apoptosis. WHSC1 triggers H3K36me2 modification at the level of the TACC3 promoter to induce TACC3 activation. TACC3 suppression similarly blocked the malignant activity of CRC cells, whereas TACC3 restoration in cells counteracted the cancer-suppressive functions of WHSC1 silencing. TACC3 levels were correlated with increased phosphorylation of the PI3K/Akt signaling pathway in cells. Likewise, WHSC1 suppression blocked tumor growth in nude mice. CONCLUSION: The results of this study revealed TACC3 as a target of WHSC1 in CRC that is positively correlated with PI3K/Akt pathway activation and tumor development.

Retroform Cervical Dystonia: Target Muscle Selection and Efficacy of Botulinum Toxin Injection.

Introduction: Retroform cervical dystonia (RCD), which includes retrocaput and retrocollis, is a rare form of cervical dystonia. Few reports have been published on RCD. The present study aimed to characterize the target muscles involved in RCD and the efficacy of botulinum toxin type A (BTX-A) injection. Methods: Patients with consecutive cervical dystonia with RCD as the most problematic feature were retrospectively analyzed over a 10-year period. Target muscles were screened and confirmed based on clinical evaluation, single-photon emission computed tomography, and electromyography. In addition, efficacy and adverse events following BTX-A injection in patients with RCD were evaluated. Results: A total of 34 patients with RCD were included, 18 of whom presented with retrocaput and 16 with retrocollis. The most frequently injected muscles in RCD were splenius capitis (SPCa, 97.1%) and semispinalis capitis (SSCa, 97.1%), followed by levator scapulae (LS, 50.0%), rectus capitis posterior major (RCPM, 47.1%), trapezius (TPZ, 41.2%), and sternocleidomastoid muscle (SCM, 41.2%). Besides cervical muscles, the erector spinae was also injected in 17.6% of patients. Most muscles were predominantly bilaterally injected. The injection schemes of retrocaput and retrocollis were similar, possibly because in patients with retrocollis, retrocaput was often combined. BTX-A injection achieved a satisfactory therapeutic effect in RCD, with an average symptom relief rate of 69.0 ± 16.7%. Mild dysphagia (17.6%) and posterior cervical muscle weakness (17.6%) were the most common adverse events. Conclusion: SPCa, SSCa, LS, RCPM, LS, and SCM were commonly and often bilaterally injected in RCD. Patients with RCD could achieve satisfactory symptom relief after BTX-A injection.

Technology-based therapy-response evaluation of axial motor symptoms under daily drug regimen of patients with Parkinson's disease.

Background: Axial disturbances are the most disabling symptoms of Parkinson's disease (PD). Kinect-based objective measures could extract motion characteristics with high reliability and validity. Purpose: The present research aimed to quantify the therapy-response of axial motor symptoms to daily medication regimen and to explore the correlates of the improvement rate (IR) of axial motor symptoms based on a Kinect camera. Materials and methods: We enrolled 44 patients with PD and 21 healthy controls. All 65 participants performed the Movement Disorder Society-Sponsored Revision of the Unified Parkinson's Disease Rating Scale part III and the Kinect-based kinematic evaluation to assess arising from a chair, gait, posture, and postural stability before and after medication. Spearman's correlation analysis and multiple linear regression model were performed to explore the relationships between motor feature IR and clinical data. Results: All the features arising from a chair (P = 0.001), stride length (P = 0.001), velocity (P < 0.001), the height of foot lift (P < 0.001), and turning time (P = 0.001) improved significantly after a daily drug regimen in patients with PD. In addition, the anterior trunk flexion (lumbar level) exhibited significant improvement (P = 0.004). The IR of the axial motor symptoms score was significantly correlated with the IRs of kinematic features for gait velocity, stride length, foot lift height, and sitting speed (r s = 0.345, P = 0.022; r s = 0.382, P = 0.010; r s = 0.314, P = 0.038; r s = 0.518, P < 0.001, respectively). A multivariable regression analysis showed that the improvement in axial motor symptoms was associated with the IR of gait velocity only (ß = 0.593, 95% CI = 0.023-1.164, P = 0.042). Conclusion: Axial symptoms were not completely drug-resistant, and some kinematic features can be improved after the daily medication regimen of patients with PD.

A summary index derived from Kinect to evaluate postural abnormalities severity in Parkinson's Disease patients.

Postural abnormalities are common disabling motor complications affecting patients with Parkinson's disease (PD). We proposed a summary index for postural abnormalities (IPA) based on Kinect depth camera and explored the clinical value of this indicator. Seventy individuals with PD and thirty age-matched healthy controls (HCs) were enrolled. All participants were tested using a Kinect-based system with IPA automatically obtained by algorithms. Significant correlations were detected between IPA and the Movement Disorder Society-Sponsored Revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS) total score (rs = 0.369, p = 0.002), MDS-UPDRS-III total score (rs = 0.431, p < 0.001), MDS-UPDRS-III 3.13 score (rs = 0.573, p < 0.001), MDS-UPDRS-III-bradykinesia score (rs = 0.311, p = 0.010), the 39-item Parkinson's Disease Questionnaire (PDQ-39) (rs = 0.272, p = 0.0027) and the Berg Balance Scale (BBS) score (rs = -0.350, p = 0.006). The optimal cut-off value of IPA for distinguishing PD from HCs was 12.96 with a sensitivity of 97.14%, specificity of 100.00%, area under the curve (AUC) of 0.999 (0.997-1.002, p < 0.001), and adjusted AUC of 0.998 (0.993-1.000, p < 0.001). The optimal cut-off value of IPA for distinguishing between PD with and without postural abnormalities was 20.14 with a sensitivity, specificity, AUC and adjusted AUC of 77.78%, 73.53%, 0.817 (0.720-0.914, p < 0.001), and 0.783 (0.631-0.900, p < 0.001), respectively. IPA was significantly correlated to the clinical manifestations of PD patients, and could reflect the global severity of postural abnormalities in PD with important value in distinguishing PD from HCs and distinguishing PD with postural abnormalities from those without.

U-Shaped Relationship of Rare Earth Element Lanthanum and Oral Cancer Risk: A Propensity Score-Based Study in the Southeast of China.

As an important rare earth element (REE) extensively applied to industry, agriculture, and medicine, lanthanum (La) has attracted a host of health concerns. This study aimed to explore the relationship between La exposure and the risk of developing oral cancer through a case-control study with a large sample size. Serum La levels of 430 oral cancer patients and 1,118 healthy controls were detected by inductively coupled plasma mass spectrometry (ICP-MS). The association of La level with the risk of oral cancer was assessed in two ways: (1) as a continuous scale based on restricted cubic splines (RCS); (2) as a priori defined centile categories using multivariate logistic regression model, based on propensity score matching (PSM) and inverse probability of treatment weighting (IPTW). The RCS revealed a non-linear U-shaped relationship between serum La and oral cancer risk. Serum La deficiency or excess was associated with an increased risk of oral cancer. When the La level was analyzed as a categorical variable, a similar U-shaped association was observed. Of note, compared to those with La concentrations of 0.243-0.341 µg/L (reference quantiles, 41st-60th), the risk was increased in those with the lower or higher quantiles (0.132-0.242 µg/L vs. 0.243-0.341 µg/L: OR = 1.80, 95%CI: 1.07-3.02; 0.342-0.497 µg/L vs. 0.243-0.341 µg/L: OR = 2.30, 95%CI: 1.38-3.84). The results were generally consistent with the PSM and IPTW analyses. This preliminary study provides strong evidence that there was a U-shaped relationship between serum La levels and oral cancer risk. Much additional work is warranted to confirm our findings.

Association Between Dietary Fatty Acid Pattern and Risk of Oral Cancer.

Objective: To investigate the association between dietary fatty acid (FA) patterns and the risk of oral cancer. Method: A case-control study which included 446 patients with oral cancer and 448 controls subjects was conducted in Southeast China. A structured food frequency questionnaire was used to assess the dietary FA consumption before cancer diagnosis. FA patterns were identified using the principal component analysis, and the relationship between the dietary FA patterns and oral cancer was analyzed by logistic regression. Results: General differences in FA intake were observed between the patient and control groups. The intakes of saturated FAs (SFAs) C14:0, C16:0, C18:0, and monounsaturated FA C18:1 were higher in the patient group than the control group (p < 0.001). Four FA patterns were derived by principal component analysis. The "SFA" pattern, "Polyunsaturated FA" pattern, "Monounsaturated FA" pattern, and "Medium- and long-chain FA" pattern, which could explain 75.7% of the variance of the dietary FA intake, were submitted to logistic regression analysis. A positive association was observed between the "SFA" pattern and oral cancer risk. Compared with the lowest quartile score, the OR of the highest quartile score was 3.71 (95%CI: 2.31, 5.94, P trend < 0.001) in the multivariate logistic regression model. No significant association was found among the other three patterns and oral cancer risk. Conclusions: General differences in dietary FA intake were observed between patients with oral cancer and controls. A positive association between the "SFA" pattern and risk of oral cancer was observed after adjusting for potential confounders.

Changes of T lymphocyte subpopulations and their roles in predicting the risk of Parkinson's disease.

T lymphocytes are involved in the pathogenesis of Parkinson's disease (PD), while the heterogeneity of T-cell subpopulations remains elusive. In this study, we analyzed up to 22 subpopulations of T lymphocytes in 115 PD patients and 60 matched healthy controls (HC) using flow cytometry. We found that PD patients exhibited decreased naïve CD8+ T cells (CD3+ CD8+ CD45RA+ CD45RO-) and increased late-differentiated CD4+ T cells (CD3+ CD4+ CD28- CD27-), compared to HC, which were not affected by anti-parkinsonism medication administration. The proportion of naïve CD8+ T cells in PD patients was positively correlated with their severity of autonomic dysfunction and psychiatric complications, but negatively associated with the severity of rapid eye movement and sleep behavior disorder. The proportion of late-differentiated CD4+ T cells was negatively correlated with the onset age of the disease. We further developed individualized PD risk prediction models with high reliability and accuracy on the base of the T lymphocyte subpopulations. These data suggest that peripheral cellular immunity is disturbed in PD patients, and changes in CD8+ T cells and late-differentiated CD4+ T cells are representative and significant. Therefore, we recommend naïve CD8 + and late-differentiated CD4+ T cells as candidates for multicentric clinical study and pathomechanism study of PD.

SMYD2 epigenetically activates MEX3A and suppresses CDX2 in colorectal cancer cells to augment cancer growth.

Dysfunction of the protein methyltransferase SET and MYND domain-containing protein 2 (SMYD2) is frequently linked to multiple diseases including cancer. The study focused on the role of SMYD2 in colorectal cancer (CRC) development. SMYD2 was expressed at high levels in CRC tissues and cells. Knockdown of SMYD2 in LOVO cells reduced cell proliferation, migration and invasiveness in vitro and it suppressed xenograft tumorigenesis in vivo. Overexpression of SMYD2 in HCT116 cells led to inverse trends. Mex-3 RNA binding family member A (MEX3A) was predicted as a target of SMYD2. Chromatin immunoprecipitation (ChIP)-reverse transcription quantitative polymerase chain reaction (qPCR) and cellular assays were performed and validated that SMYD2 activated MEX3A expression by promoting H3K36me2 modification on its promoter. Data in the STRING bioinformatics system indicated caudal type homeobox 2 (CDX2) as an important MEX3A-related gene. Silencing of MEX3A alone blocked proliferation and growth of CRC cells in vitro and in vivo, whereas MEX3A overexpression promoted cell growth by suppressing CDX2. In rescue experiments, MEX3A silencing suppressed the cell growth augmented by SMYD2, and CDX2 downregulation restored the malignance of cancer cells inhibited by MEX3A silencing. Taken together, this study reports that SMYD2-mediated activation of MEX3A augments progression of CRC by suppressing CDX2.