Neurosyphilis with oral­facial­lingual dyskinesia: A case report.

The present study describes the case of a 52-year-old male patient who presented with subacute onset dysarthria and oral-facial-lingual dyskinesia, with normal blood glucose and acanthocyte levels, and no history of drug use. The patient tested negative for autoimmune encephalitis-related antibodies and paraneoplastic-related antibodies. The level of cerebrospinal fluid (CSF) protein was slightly elevated, and the Treponema pallidum hemagglutination assay and rapid plasma reagin test were positive in both serum and CSF samples. After 1 month of treatment with doxycycline, the patient's oral-facial-lingual dyskinesia was significantly improved, suggesting the diagnosis of neurosyphilis.

Autoimmune glial fibrillary acidic protein astrocytosis mimicking tuberculous meningitis: a retrospective study.

BACKGROUND: This study aimed to summarize the clinical features of Autoimmune Glial Fibrillary Acidic Protein Astrocytosis mimicking tuberculosis meningitis to improve clinicians' understanding of this disease. METHODS: We retrospectively analyzed the clinical manifestations, cerebrospinal fluid results, and imaging data of five patients with Autoimmune Glial Fibrillary Acidic Protein Astrocytosis mimicking tuberculous meningitis who were admitted to Xiangya Hospital Central South University between October 2021 and July 2022. RESULTS: Five patients were aged 31-59 years, with a male-to-female ratio of 4:1. Among the cases reviewed, four had a history of prodromal infections manifesting as fever and headache. One patient developed limb weakness and numbness with clinical manifestations of meningitis, meningoencephalitis, encephalomyelitis, or meningomyelitis. Cerebrospinal fluid analysis revealed an increased cell count in five cases, with a lymphocyte majority. All five cases had a CSF protein level > 1.0 g/L, CSF/blood glucose ratio < 0.5, and two patients had CSF glucose < 2.2 mmol/L. Decreased CSF chloride was observed in three cases, while increased ADA was observed in one case. Both serum and cerebrospinal fluid were positive for anti-GFAP antibodies in three cases, while in two cases, only CSF was positive for anti-GFAP antibodies. Additionally, hyponatremia and hypochloremia were observed in three cases. No tumors were detected in any of the five patients during tumor screening, and all five cases had a good prognosis following immunotherapy. CONCLUSION: Anti-GFAP antibody testing should be routinely performed in patients with suspected tuberculosis meningitis to avoid misdiagnosis.

Prognostic nomograms integrating preoperative serum lipid derivative and systemic inflammatory marker of patients with non-metastatic colorectal cancer undergoing curative resection.

Background: Lipid metabolism and cancer-related inflammation are closely related to the progression and prognosis of colorectal cancer (CRC). Therefore, this study aims to establish novel nomograms based on the combined detection of preoperative blood lipids and systemic inflammatory indicators to predict the overall survival (OS) and cancer-specific survival (CCS) of CRC patients. Methods: A total of 523 patients with stage I-III CRC in our institute were collected from 2014 to 2018. The independent predictors for OS and CCS were determined by forward stepwise Cox regression for the establishment of prognostic models. The superiorities of different models were compared by concordance index (C-index), Akaike information criterion (AIC) and integrated discrimination improvement analysis. The performance of the nomograms based on the optimal models was measured by the plotting time-dependent receiver operating characteristic curves, calibration curves, and decision curves, and compared with the tumor-node-metastasis (TNM) staging system. The cohort was categorized into low-risk, medium-risk and high-risk groups according to the risk points of the nomogram, and analyzed using Kaplan-Meier curves and log-rank test. Results: Preoperative TG/HDL-C ratio (THR) ≥ 1.93 and prognostic nutritional index (PNI) ≥ 42.55 were independently associated with favorable outcomes in CRC patients. Six (pT stage, pN stage, histological subtype, perineural invasion, THR and PNI) and seven (pT stage, pN stage, histological subtype, perineural invasion, gross appearance, THR and PNI) variables were chosen to develop the optimal models and construct nomograms for the prediction of OS and CCS. The models had lower AIC and larger C-indexes than other models lacking either or both of THR and PNI, and improved those integrated discrimination ability significantly. The nomograms showed better discrimination ability, calibration ability and clinical effectiveness than TNM system in predicting OS and CCS, and these results were reproducible in the validation cohort. The three risk stratifications based on the nomograms presented significant discrepancies in prognosis. Conclusion: Preoperative THR and PNI have distinct prognostic value in stage I-III CRC patients. The nomograms incorporated the two indexes provide an intuitive and reliable approach for predicting the prognosis and optimizing individualized therapy of non-metastatic CRC patients, which may be a complement to the TNM staging system.

Construction of IMMS Containing Multi-site Liposomes for Dynamic Monitoring of Blood CTC in Patients with Osimertinib-resistant Non-small-cell Lung Cancer and its Mechanism.

OBJECTIVE: This article aims to establish a liquid biopsy system for gene detection of circulating tumor cells (CTC) in lung cancer, systematically analyze the significance of osimertinib resistance, and formulate an individualized diagnosis and treatment plan. METHODS: Liposome-contained magnetic microspheres coated with Fe3O4 nanoparticles were synthesized by microemulsion, and the surface was modified with EGFR antibody to form EGFR/EpCAM multi-site liposome-contained immunomagnetic microspheres (IMMSs). The CTCs were isolated and identified from peripheral blood samples and the cell lines of lung cancer patients collected by the multi-site liposome-contained IMMSs. To investigate the effects of the order of use of IMMSs sequence at different sites on the sorting and trapping efficiency of non-small-cell lung cancer (NSCLC) cells . The preliminary verification of drug-resistant gene function and dynamic monitoring of CTCs in 20 patients with EGFR-positive NSCLC were screened and statistically analyzed before and after osimertinib treatment. Sensitivity analysis and drug resistance evaluation of oxitidine were detected in vitro. RESULTS: Results showed the prepared multi-site liposome-contained IMMSs had high stability and specificity. The number of CTCs in blood samples of the patients with NSCLC was detected, revealing high sorting efficiency, and positive sorting rate reaching more than 90%. We investigated the effect of osimertinib on the HER-2 expression on the EGFR-mutated NSCLC cells and found that osimertinib increased the expression of HER-2 on the cell surface of NSCLC cell lines., And further explored the therapeutic potential of osimertinib combined with T-DM1 at different dosing times. CONCLUSION: Our results demonstrate that the prepared multi-site liposome-contained IMMSs can efficiently isolate CTCs from the peripheral blood in lung cancer. Combined with the experimental data about osimertinib can be effectively identified, the resistant genes of NSCLC including EGFR, which will provide a new scientific basis for guiding clinical medication and formulating individualized treatment plans.

Development and validation of a novel nomogram for predicting survival rate in pancreatic neuroendocrine neoplasms.

BACKGROUND: Over the past decades, the incidence and prevalence of pancreatic neuroendocrine neoplasms (pNENs) have steadily increased. However, accurate prediction of the prognosis and treatment of this condition are currently challenging. This study aims to develop and validate a personalized nomogram to predict the survival of patients with pNENs. MATERIALS AND METHODS: A total of 9739 patients with pNENs were downloaded from the Surveillance, Epidemiology, and End Results (SEER) database. Subsequently, the patients were randomly assigned to a derivation cohort (n = 6874) and a validation cohort (n = 2865). The survival of patients was assessed using the Cox proportional hazards (PHs) regression analysis. Then, the nomogram that predicted 3-and 5-year survival rates were developed in the derivation cohort. Further, the predictive performance of the nomogram was evaluated through discrimination and calibration. RESULTS: The Cox regression analysis revealed that age, differentiation, the extent of tumor, M staging, and surgery were independent prognostic predictors for pNENs. The nomogram showed superior discrimination capability than AJCC staging in both derived and validation cohorts (C-index: 0.874 versus 0.721 and 0.833 versus 0.721). The calibration curves showed that the practical and predicted survival rates effectively coincided, specifically for the 3-year survival rate. CONCLUSION: Our nomogram is a valuable tool for the prediction of the survival rate for patients with pNENs; this may promote individualized prognostic evaluation and treatment.

Crizotinib resistance conferred by BRAF V600E mutation in non-small cell lung cancer harboring an oncogenic ROS1 fusion.

Non-small cell lung cancer (NSCLC) patients with oncogenic ROS1 rearrangements would inevitably develop drug resistance and disease progression after receiving targeted oncogene therapy. Here, we present a metastatic lung adenocarcinoma patient harboring a CD74-ROS1 fusion who initially responded to crizotinib and then developed resistance after acquiring a rarely reported BRAF V600E mutation.

A Case of Severe Diabetic Ketoacidosis Associated with Pembrolizumab Therapy in a Patient with Metastatic Melanoma.

Pembrolizumab, a monoclonal antibody against programmed cell death-1 receptor, was licensed for advanced cancers. Although the use of pembrolizumab can enhance the effect of cancer treatment, it can increase immune-related adverse events. We describe an elderly woman who developed ketoacidosis after receiving pembrolizumab to treat metastatic melanoma. In the presentation, laboratory analysis showed that hyperglycemia and anion gap metabolic acidosis was consistent with diabetic ketoacidosis. Except for pembrolizumab, no other predisposing factors were found. The blood glucose levels before using pembrolizumab were normal. The patient responded well to intravenous fluids, insulin therapy, and treatment to correct electrolyte disturbances. She was diagnosed with severe diabetic ketoacidosis (DKA) because of new-onset diabetes mellitus which associated with pembrolizumab therapy. Two months after she was discharged from the hospital, she continued to take insulin as well as metformin to treat her diabetes. Clinicians need to be alert about diabetes mellitus and ketoacidosis for patients undergoing pembrolizumab treatment.

A clinical prediction nomogram to assess risk of colorectal cancer among patients with type 2 diabetes.

Colorectal cancer remains a major health burden worldwide and is closely related to type 2 diabetes. This study aimed to develop and validate a colorectal cancer risk prediction model to identify high-risk individuals with type 2 diabetes. Records of 930 patients with type 2 diabetes were reviewed and data were collected from 1 November 2013 to 31 December 2019. Clinical and demographic parameters were analyzed using univariable and multivariable logistic regression analysis. The nomogram to assess the risk of colorectal cancer was constructed and validated by bootstrap resampling. Predictors in the prediction nomogram included age, sex, other blood-glucose-lowering drugs and thiazolidinediones. The nomogram demonstrated moderate discrimination in estimating the risk of colorectal cancer, with Hosmer-Lemeshow test P = 0.837, an unadjusted C-index of 0.713 (95% CI 0.670-0.757) and a bootstrap-corrected C index of 0.708. In addition, the decision curve analysis demonstrated that the nomogram would be clinically useful. We have developed a nomogram that can predict the risk of colorectal cancer in patients with type 2 diabetes. The nomogram showed favorable calibration and discrimination values, which may help clinicians in making recommendations about colorectal cancer screening for patients with type 2 diabetes.

Nomogram for Predicting Risk of Digestive Carcinoma Among Patients with Type 2 Diabetes.

PURPOSE: Digestive carcinomas remain a major health burden worldwide and are closely related to type 2 diabetes. The aim of this study was to develop and validate a digestive carcinoma risk prediction model to identify high-risk individuals among those with type 2 diabetes. PATIENTS AND METHODS: The prediction model was developed in a primary cohort that consisted of 655 patients with type 2 diabetes. Data were collected from November 2013 to December 2018. Clinical parameters and demographic characteristics were analyzed by logistic regression to develop a model to predict the risk of digestive carcinomas; then, a nomogram was constructed. The performance of the nomogram was assessed with respect to calibration, discrimination, and clinical usefulness. The results were internally validated by a bootstrapping procedure. The independent validation cohort consisted of 275 patients from January 2019 to December 2019. RESULTS: Predictors in the prediction nomogram included sex, age, insulin use, and body mass index. The model showed good discrimination (C-index 0.747 [95% CI, 0.718-0.791]) and calibration (Hosmer-Lemeshow test P=0.541). The nomogram showed similar discrimination in the validation cohort (C-index 0.706 [95% CI, 0.682-0.755]) and good calibration (Hosmer-Lemeshow test P=0.418). Decision curve analysis demonstrated that the nomogram would be clinically useful. CONCLUSION: We developed a low-cost and low-risk model based on clinical and demographic parameters to help identify patients with type 2 diabetes who might benefit from digestive cancer screening.

Bacillus cereus isolated from a positive bone tissue culture in a patient with osteolysis and high-titer anti-interferon-γ autoantibodies: A case report.

RATIONALE: Bacillus cereus (B cereus) is an aerobic or facultative anaerobic gram-positive, spore-forming bacterium. It can cause fatal disease and generally manifests as 3 distinct syndromes: food intoxication, localized infection, and systemic infection. It is a rare infection that can occur in immunocompetent persons with osteolytic and high-titer anti-IFN-γ autoantibodies. PATIENT CONCERNS: We reported a case of an HIV-negative 24-year old man with an interrupted fever and a 20-day history of progressive ache in the right thigh and high-titer anti-IFN-γ autoantibodies. Magnetic resonance imaging, X-radiography, high-resolution computed tomography, and 3-dimensional reconstruction of the bone showed multiple lucent defects with moth-eaten destruction of the bone and cortical substance of bone in the right femur. Emission CT showed significantly increased uptake in the femur. DIAGNOSIS AND INTERVENTIONS: The patient was originally misdiagnosed with osteosarcoma; acute osteomyelitis was also considered. He received intravenous piperacillin, sulbactam, and levofloxacin during hospitalization; however, he did not respond to the 3-week antibiotic course and his condition worsened. After cultures from incisional biopsy specimens were obtained from the femoral cavity, B cereus-induced osteomyelitis was diagnosed. He received intravenous injections of moxifloxacin 400 mg qd for 4 weeks and oral moxifloxacin 400 mg qd for 8 weeks. OUTCOMES: The patient's symptoms and signs improved. His X-radiography, HRCT, MRI, and 3-dimensional reconstruction of the bone showed absolute absorption in the right femur. However, the anti-IFN-γ autoantibody titer was still high. No recurrence was observed after 24 months of follow-up. He is still undergoing follow-up at this time. LESSONS: This is the first case involving a patient with B cereus infection showing a high titer of anti-IFN-γ autoantibodies. B cereus infection can involve the bone, leading to osteolysis in HIV-negative individuals. Although this patient was HIV-negative and had no other comorbidities, the presence of high titer anti-IFN-γ autoantibodies may be the primary reason for B cereus infection. Clinicians should pay more attention to the identification of osteolytic destruction caused by tumor and infection.

The role of free triiodothyronine in high-density lipoprotein cholesterol metabolism.

The aim of this study was to analyze the correlation between free triiodothyronine (FT3), free thyroxine (FT4), thyroid-stimulating hormone (TSH), and serum high-density lipoprotein cholesterol (HDL-C), and to explore the significance of FT3 in HDL-C metabolism in people with normal thyroid function.A total of 461 Chinese, aged ≥28 years, from a college community in Nanning, Guangxi, were enrolled for a cross-sectional epidemiological investigation of metabolic syndrome from October 2016 to November 2016. Height, weight, blood pressure, total cholesterol, HDL-C, triglyceride (TG), fasting glucose (FPG), FT3, FT4, and TSH were measured for each individual. Multiple linear regression analysis was used to evaluate the correlation between FT3, FT4, TSH, and HDL-C.After controlling for sex, age, body mass index (BMI), smoking, drinking, and other confounding factors, FT3 was negatively correlated with HDL-C levels, on average, when FT3 increased by 1 pmol/L, HDL-C decreased by 0.143 mmol /L with a statistically significant difference (P < .001). FT4 was positively correlated with HDL-C, and HDL-C increased by 0.016 mmol/L for every 1-pmol/L increase in FT4. TSH was negatively correlated with HDL-C, and HDL-C decreases by 0.010 mmol/L for every 1-µIU/mL increase in TSH, but the differences were not statistically significant (P > .05).FT3 may be an important factor affecting HDL-C levels. The detection and regulation of thyroid hormone (especially FT3) in patients with low HDL-C, as well as the detection of HDL-C in patients with thyroid dysfunction, is important to prevent the occurrence of cardiovascular diseases.

MiR-519b-3p Inhibits the Proliferation and Invasion in Colorectal Cancer via Modulating the uMtCK/Wnt Signaling Pathway.

Dysregulation of microRNAs (miRNAs) and their targeted downstream genes is involved in the carcinogenesis and progression of colorectal cancer (CRC). miR-519b-3p has been reported to play an important role in several cancers. However, its function in CRC is unclear. In this study, we detected the expression of miR-519b-3p in CRC tissues and cell lines, and determined the potential role of miR-519b-3p in cell proliferation and invasion in CRC. Also, the downstream gene of miR-519b-3p was determined. Our results showed that miR-519b-3p was notably reduced in CRC specimens and cell lines. Overexpression of miR-519b-3p inhibited the proliferation and invasion of RKO and DLD-1 cells, whereas knockdown of miR-519b-3p had the contrary effect. The ubiquitous mitochondrial creatine kinase (uMtCK) was identified as a direct target of miR-519b-3p in CRC using luciferase assay. Additionally, miR-519b-3p expression was negatively correlated with uMtCK expression in CRC specimens. Notably, the miR-519b-3p suppressed the uMtCK/Wnt signaling pathway in CRC cells, thereby suppressing CRC cell proliferation and invasion. The inhibition of uMtCK by miR-519b-3p may provide a promising option for the treatment of CRC.

An occult urothelial carcinoma with wide multiorgan metastases and its genetic alteration profiling: Case report and literature review.

RATIONALE: Urothelial carcinoma, also named transitional cell carcinoma, is the most frequent occurring malignancy in the urinary system. It mainly invades the surrounding tissues and metastasizes to distant organs in later stages. PATIENT CONCERNS: Here, we presented an unusual case of occult urothelial carcinoma primarily manifested as a multiorgan metastatic cancer in a 59-year-old man. The patient complained of pain on the left thigh root for a month. The imaging and histopathological examination revealed multiple malignancies in lung, bone, and liver. DIAGNOSES: The histological evaluation and the immunohistochemistry (IHC) profile of liver, lung, and bone were consistent with the diagnosis of metastases from the original urothelial cancer, while imaging examination was not able to detect a primary lesion in the urinary system. INTERVENTIONS: Based on the mutation of STK11 M51Ifs*106 detected by next generation sequencing (NGS), we started targeted therapy with everolimus. OUTCOMES: The patient deteriorated after 3 months of treatment and passed away. LESSONS: In this initial report of occult urothelial carcinoma, we obtained information on genetic variations of tumor tissue which could provide important information for subsequent studies on this kind of disease.

Downregulation of lncRNA-SRA participates in the development of cardiovascular disease in type II diabetic patients.

Long non-coding RNA steroid receptor RNA activator (lncRNA-SRA) has been proven to regulate vascular smooth muscle cell (VSMC) proliferation, indicating its possible involvement in cardiovascular disease. Diabetes is a major cause of cardiovascular disease. The aim of the present study was to investigate the involvement of lncRNA-SRA in type II diabetic cardiovascular disease. The plasma levels of lncRNA-SRA were identified to be significantly lower in patients with type II diabetic cardiovascular disease compared with those in type II diabetic patients without any obvious complications and in healthy controls. A 5-year follow-up study revealed that low vs. high expression levels of lncRNA-SRA were associated with an increased incidence of cardiovascular disease in type II diabetic patients. High-glucose treatment did not significantly affect the expression of lncRNA-SRA in human VSMCs in vitro. However, ectopic overexpression of lncRNA-SRA increased the viability of human VSMCs in a high-glucose environment. It was concluded that downregulation of lncRNA-SRA may participate in the development of cardiovascular disease in type II diabetic patients.

ALK-rearranged lung adenocarcinoma patient with development of severe sinus bradycardia after treatment with crizotinib: A case report.

RATIONALE: The anaplastic lymphoma kinase (ALK) rearrangements represent a subtype of nonsmall-cell lung cancer (NSCLC), and targeting ALK has radically changed the treatment of NSCLC. Crizotinib, as an ALK inhibitor, has been used in the treatment of ALK-rearranged NSCLC for several years and some adverse effects should be given attention. PATIENT CONCERNS: A 64-year-old woman with a no-smoking history visited hospital in November 2016 because of a persistent cough, expectoration, and progressive dysphagia for 2 months. DIAGNOSES AND INTERVENTIONS: She was diagnosed with primary lung adenocarcinoma, accompanied by pleural and bone metastases. After receiving chemotherapy for nearly 1 year, she showed progressive disease. DNA-sequencing identified an intergenic ALK rearrangement. Surprisingly, RNA-sequencing revealed the EML4-ALK fusion transcript. Subsequently, this patient switched to crizotinib therapy. OUTCOMES: The patient achieved partial response after 1-month treatment. However, this patient suffered a severe sinus bradycardia after 4 months of treatment. When reducing the dose of crizotinib, the side effect was alleviated and this patient showed stable disease until now. LESSONS: Given that the severe sinus bradycardia was an unusual adverse effect, physicians should be aware of these side effects when using crizotinib. Moreover, it should be noted that this patient harbored an intergenic ALK rearrangement identified by DNA-sequencing, but EML4-ALK fusion transcript verified by RNA-sequencing. However, the mechanism remains unknown and requires further research.

Two Unusual Cases of Human Immunodeficiency Virus-Negative Patients with Talaromyces marneffei Infection.

Talaromyces marneffei (formerly known as Penicillium marneffei) is a dimorphic fungus endemic in south and southeast Asia. It is not only commonly found in human immunodeficiency virus (HIV)-infected patients, but also among HIV-negative immunocompromised patients. The infection caused by this pathogen can disseminate hematogenously to other locations. Herein, we report for the first time two cases complicated with a rare disease or involving a rare site: in the first case, T. marneffei infection was complicated by Langerhans cell histiocytosis, whereas the second case showed clear etiological evidence of pleural nodules and pleural effusion caused by T. marneffei and diagnosed by thoracoscopic pleural biopsy.

Prevalence of diabetes and determinants: evidence from a minority region in People's Republic of China.

BACKGROUND: This study aimed to examine the prevalence of diabetes mellitus and other categories of glucose intolerance (impaired glucose tolerance and impaired fasting glucose) and explore the risk factors in an ethnic minority region, Guangxi Zhuang Autonomous Region, People's Republic of China. METHODS: A population-based study enrolled 53,270 residents older than 5 years in Guangxi, People's Republic of China. The prevalence of diabetes was calculated using the 1999 World Health Organization (WHO) oral glucose tolerance test diagnostic criteria. RESULTS: Among 53,270 individuals, the prevalence of diabetes, impaired glucose tolerance, and impaired fasting glucose was 5.96%, 7.36%, and 2.62%, respectively. Of the 3,173 individuals with diabetes mellitus, 696 (21.94%) were found to have a history of diabetes and 2,477 (78.06%) were newly diagnosed. A lower prevalence was found in Zhuang ethnic minority people compared with the majority of Han people. The prevalence was significantly associated with age, body mass index, waist-to-hip ratio, dyslipidemia, medical history of hypertension, and family history of diabetes. CONCLUSION: Guangxi shows a rapidly rising prevalence of diabetes. Weight control and blood lipid control are important to decrease the rapidly increasing prevalence of diabetes in Guangxi, an ethnic minority region.