Simultaneous SERS Sensing of Cysteine and Homocysteine in Blood Based on the CBT-Cys Click Reaction: Toward Precisive Diagnosis of Schizophrenia.

At present, there is a lack of sufficiently specific laboratory diagnostic indicators for schizophrenia. Serum homocysteine (Hcy) levels have been found to be related to schizophrenia. Cysteine (Cys) is a demethylation product in the metabolism of Hcy, and they always coexist with highly similar structures in vivo. There are few reports on the use of Cys as a diagnostic biomarker for schizophrenia in collaboration with Hcy, mainly because the rapid, economical, accurate, and high-throughput simultaneous detection of Cys and Hcy in serum is highly challenging. Herein, a click reaction-based surface-enhanced Raman spectroscopy (SERS) sensor was developed for simultaneous and selective detection of Cys and Hcy. Through the efficient and specific CBT-Cys click reaction between the probe containing cyan benzothiazole and Cys/Hcy, the tiny methylene difference between the molecular structures of Cys and Hcy was converted into the difference between the ring skeletons of the corresponding products that could be identified by plasmonic silver nanoparticle enhanced molecular fingerprint spectroscopy to realize discriminative detection. Furthermore, the SERS sensor was successfully applied to the detection in related patient serum samples, and it was found that the combined analysis of Cys and Hcy can improve the diagnostic accuracy of schizophrenia compared to a single indicator.

A multi-parameter intrahepatic cholangiocarcinoma scoring system based on modified contrast-enhanced ultrasound LI-RADS M criteria for differentiating intrahepatic cholangiocarcinoma from hepatocellular carcinoma.

PURPOSE: To develop a multi-parameter intrahepatic cholangiocarcinoma (ICC) scoring system and compare its diagnostic performance with contrast-enhanced ultrasound (CEUS) liver imaging reporting and data system M (LR-M) criteria for differentiating ICC from hepatocellular carcinoma (HCC). METHODS: This retrospective study enrolled 62 high-risk patients with ICCs and 62 high-risk patients with matched HCCs between January 2022 and December 2022 from two institutions. The CEUS LR-M criteria was modified by adjusting the early wash-out onset (within 45 s) and the marked wash-out (within 3 min). Then, a multi-parameter ICC scoring system was established based on clinical features, B-mode ultrasound features, and modified LR-M criteria. RESULT: We found that elevated CA 19-9 (OR=12.647), lesion boundary (OR=11.601), peripheral rim-like arterial phase hyperenhancement (OR=23.654), early wash-out onset (OR=7.211), and marked wash-out (OR=19.605) were positive predictors of ICC, whereas elevated alpha-fetoprotein (OR=0.078) was a negative predictor. Based on these findings, an ICC scoring system was established. Compared with the modified LR-M and LR-M criteria, the ICC scoring system showed the highest area under the curve (0.911 vs. 0.831 and 0.750, both p<0.05) and specificity (0.935 vs. 0.774 and 0.565, both p<0.05). Moreover, the numbers of HCCs categorized as LR-M decreased from 27 (43.5%) to 14 (22.6%) and 4 (6.5%) using the modified LR-M criteria and ICC scoring system, respectively. CONCLUSION: The modified LR-M criteria-based multi-parameter ICC scoring system had the highest specificity for diagnosing ICC and reduced the number of HCC cases diagnosed as LR-M category.

Non-invasive imaging in the diagnosis of combined hepatocellular carcinoma and cholangiocarcinoma.

Combined hepatocellular-cholangiocarcinoma (cHCC-CC) is a rare type of primary liver cancer. It is a complex "biphenotypic" tumor type consisting of bipotential hepatic progenitor cells that can differentiate into cholangiocytes subtype and hepatocytes subtype. The prognosis of patients with cHCC-CC is quite poor with its specific and more aggressive nature. Furthermore, there are no definite demographic or clinical features of cHCC-CC, thus a clear preoperative identification and accurate non-invasive imaging diagnostic analysis of cHCC-CC are of great value. In this review, we first summarized the epidemiological features, pathological findings, molecular biological information and serological indicators of cHCC-CC disease. Then we reviewed the important applications of non-invasive imaging modalities-particularly ultrasound (US)-in cHCC-CC, covering both diagnostic and prognostic assessment of patients with cHCC-CC. Finally, we presented the shortcomings and potential outlooks for imaging studies in cHCC-CC.

Tubal ectopic pregnancy: a retrospective cohort study on clinical characteristics, treatment options and reproductive outcomes within 5 years.

PURPOSE: To investigate the association between different treatments of tubal ectopic pregnancy (EP) -expectant management, methotrexate (MTX), selected or recommended laparoscopic surgery-and the subsequent reproductive outcomes. METHODS: We conducted a retrospective cohort study including 228 EPs. The patients were divided into four treatment groups: 28 (12.3%) with expectant management successfully, 60 (26.3%) with MTX successfully, 140 patients with laparoscopic salpingectomy, of which 47 (20.6%) were assigned to selected surgery group because they opted for surgical treatment versus MTX, 93 (40.8%) were assigned to recommended surgery group as recommended by the attending physician. RESULTS: The recommended surgery group had the lowest rate of intrauterine pregnancy (IUP) (77.42%) and live birth (LB) (72.04%), while the incidence of recurrent EP (REP) (20.43%) was the highest, but the statistical differences were not significant. We did not observe significant differences of the EP-IUP time interval, rates of LB and miscarriage (MIS) between the four groups. Compared to the MTX group, recommended surgery was negatively associated with IUP (adjusted OR, 95%CI: 0.34, 0.11-1.03) and LB (0.35, 0.14-0.92), while it had higher risk for REP (3.48, 1.03-11.74) in the subsequent pregnancy. Further, compared to selective surgery group, recommended surgery was negatively associated with IUP (0.15, 0.03-0.68) and LB (0.23, 0.07-0.74), while it had higher risk for REP (6.83, 1.43-32.67) in the subsequent pregnancy. Expectant treatment was negatively associated with assisted reproductive technology (ART) (0.08, 0.02-0.40) compared with MTX. Of the185 patients who had LBs, all adverse outcomes were not statistically different between the four groups. CONCLUSION: Patients with recommended laparoscopic salpingectomy had worse reproductive outcomes than the other treatment groups. The disease status of EP may play an important role in the association rather than the surgery alone.

Iatrogenic Vocal Fold Paralysis: A Population-Based Cohort Study in Taiwan.

OBJECTIVE: Iatrogenic vocal fold paralysis is an important issue in laryngology, yet there are few population-based studies regarding the epidemiology. This study used a nationwide population-based claims database (the National Health Insurance Research Database) to investigate the epidemiology of iatrogenic unilateral and bilateral vocal fold paralysis (UVFP/BVFP) among the general adult population in Taiwan. METHOD: This study analyzed patients (20-90 years old) who underwent thyroid, parathyroid, thoracic, cardiac, or anterior cervical spine operations with vocal fold paralysis among adults in Taiwan from January 1, 2007 to December 31, 2013. The codes for vocal fold paralysis were defined by International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM). Claims data in the Taiwan National Health Insurance Research Database were used. RESULTS: The most commonly performed operations which were related to vocal fold paralysis in Taiwan were, in descending order of frequency, thyroid, cervical spine, cardiac, thoracic (esophagectomy), and parathyroid operations. The operations that put laryngeal nerves at risk (ONRs) most commonly associated with a diagnosis of UVFP were, in descending order of frequency, thoracic, thyroid, parathyroid, cardiac, and cervical spine. For both UVFP and BVFP, the most commonly associated age group was 51 to 60. For both UVFP and BVFP, the more commonly associated sex was women. Increased length of stay was associated with a higher incidence of UVFP and BVFP. Charlson medical co-morbidity index (CCI) was not associated with UVFP but BVFP was associated with higher Charlson medical co-morbidity scores. CONCLUSIONS: Thyroid operations, age 51 to 60, longer hospital stays are associated with vocal fold paralysis. Overall women are more surgically affected than men. This is the first population-based study of iatrogenic vocal fold paralysis.

Pan-Cancer Prognostic Role and Targeting Potential of the Estrogen-Progesterone Axis.

INTRODUCTION: Estrogen receptors (ESRs) and progesterone receptors (PGRs) are associated with the development and progression of various tumors. The feasibility of ESRs and PGRs as prognostic markers and therapeutic targets for multiple cancers was evaluated via pan-cancer analysis. METHODS: The pan-cancer mRNA expression levels, genetic variations, and prognostic values of ESR1, ESR2, and PGR were analyzed using the Gene Expression Profiling Interactive Analysis 2 (GEPIA2) and cBioPortal. The expression levels of ERa, ERb, and PGR proteins were detected by immunohistochemical staining using paraffin-embedded tissue specimens of ovarian serous cystadenocarcinoma (OV) and uterine endometrioid adenocarcinoma (UTEA). Correlation between immunomodulators and immune cells was determined based on the Tumor and Immune System Interaction Database (TISIDB). RESULTS: ESR1, ESR2, and PGR mRNAs were found to be differentially expressed in different cancer types, and were associated with tumor progression and clinical prognosis. ERa, ERb, and PGR proteins were further determined to be significantly differentially expressed in OV and UTEA via immunohistochemical staining. The expression of ERa protein was positively correlated with a high tumor stage, whereas the expression of PGR protein was conversely associated with a high tumor stage in patients with OV. In patients with UTEA, the expression levels of both ERa and PGR proteins were conversely associated with tumor grade and stage. In addition, the expression levels of ESR1, ESR2, and PGR mRNAs were significantly associated with the expression of immunomodulators and immune cells. CONCLUSION: ESR1, ESR2, and PGR are potential prognostic markers and therapeutic targets, as well as important factors for the prediction, evaluation, and individualized treatment in several cancer types.

BST1 rs4698412 allelic variant increases the risk of gait or balance deficits in patients with Parkinson's disease.

AIMS: We aimed to explore effects of bone marrow stromal cell antigen-1 (BST1) rs4698412 allelic variant on brain activation and associative clinical symptoms in Parkinson's disease (PD). METHODS: A total of 49 PD patients and 47 healthy control (HC) subjects were recruited for clinical evaluations, blood samples collection for genotypes, and resting-state functional MRI (rs-fMRI) scans. Based on BST1 rs4698412 allelic variant (G â†’ A), participants were further divided into 18 PD-GG, 31 PD-GA/AA, 20 HC-GG, and 27 HC-GA/AA carriers, which respectively indicated subjects carrying ancestral or risk allele in that locus in PD or HC. Two-way analysis of covariance (ANCOVA) was applied to investigate main effects and interactions between PD and BST1 rs4698412 allelic variant on brain function via amplitude of low-frequency fluctuations (ALFF). Spearman's correlations were then utilized to detect associations between interactive brain regions and clinical symptoms. RESULTS: Compared to HC subjects, PD patients exhibited increased ALFF values in left cerebellum_8 and cerebellum_9. Significant interaction was in right lingual gyrus, where there were the lowest ALFF values and ALFF values were only negatively associated with Timed Up and Go (TUG) test time in PD-GA/AA subgroup. CONCLUSION: BST1 rs4698412-modulated lingual gyrus functional alterations could be related to gait and balance dysfunction in PD.

Clinical efficacy of concurrent bevacizumab for malignant ascites in nonsquamous cell carcinoma of the lung.

PURPOSE: Lung cancer with malignant peritoneal carcinomatosis and malignant ascites is rare, often indicates the terminal stage, and is refractory to treatment. The median survival time of lung cancer patients with malignant ascites has been reported to be as short as 15 days to 2 months in retrospective studies. METHODS: We reviewed all lung cancer patients who had cytologically or pathologically proven malignant ascites and received aggressive therapy including chemotherapy, anti-angiogenesis agents and target therapy at a Taiwan hospital from January 2015 to December 2017. In addition, we searched PubMed using the terms "lung cancer," "peritoneal carcinomatosis" and "malignant ascites" to find other studies reporting experience of such treatment. RESULTS: Three consecutive lung cancer patients with malignant ascites (3/265, 1.13%) were included in this case series study, all of whom received bevacizumab with three other drugs (erlotinib, afatinib and gemcitabine). All of the patients showed a good response to treatment with a marked decrease in ascites. Two of the patients had a long progression-free survival time of more than 5 months. In the literature review, several cases reports and case series documented the treatment efficacy, however no prospective or retrospective studies reported treatment strategies. CONCLUSIONS: Aggressive treatment for lung cancer with malignant ascites is encouraged when possible. Bevacizumab-based treatment may serve as one effective treatment strategy for non-squamous cell lung carcinoma with malignant ascites. Further prospective trials are urgently needed.

Regression of a metastatic lung mass after receiving whole brain irradiation: Can the abscopal effect cross the blood-brain barrier?

An abscopal effect refers to distant tumor regression after localized irradiation. The mechanism is thought to be via local radiotherapy triggering the immune system which then attacks distant tumor sites. Only several cases of solid tumors with an abscopal effect have been reported in the past few decades, and whether an abscopal effect can cross the blood-brain barrier is still unknown. Herein, we present a female patient who was admitted due to unsteady gait and dyspnea. Chest X-ray (CXR) and chest CT showed a huge lung mass with left lung collapse and multiple liver masses. Brain MRI also showed multiple brain metastases. A bronchoscopic biopsy proved metastatic adenocarcinoma from colorectal cancer based on immunohistochemical staining. She therefore received 30 Gy (10 fractions) for the brain metastases; however, she refused to receive any systemic therapy for her lung mass and asked for hospice care. She was therefore transferred to a nursing home and was lost to follow-up. She returned 2 months later due to right pneumonia with fever and productive cough. Surprisingly, her left lung mass had markedly regressed even though she had not received any additional systemic anticancer therapy. This may be the first case of an abscopal effect after receiving whole brain irradiation for brain metastases.

Metformin decreases lung cancer risk in diabetic patients in a dose-dependent manner.

OBJECTIVES: Higher risk of lung cancer has been noted in patients with type 2 diabetes mellitus (DM). Some observational studies have shown a reduced risk of lung cancer in DM patients taking metformin, but a dose-response relationship has never been reported. The aim of this study is to exam the association between the dose of metformin and the incidence of lung cancer in a Chinese population. MATERIALS AND METHODS: The dataset used for this nationwide population-based study is a cohort of 1 million subjects randomly sampled from individuals enrolled in the Taiwan National Health Insurance system. We enrolled all subjects with newly diagnosed type 2 DM between 1997 and 2007. Subjects with a diagnosis of neoplasm before DM diagnosis, those using metformin before DM diagnosis, those with polycystic ovary syndrome, and those with a DM diagnosis before their 15 years of age were excluded. The demographic data and duration, cumulative dose and intensity of metformin use were compared between patients developing lung cancer and those without lung cancer. RESULTS: Totally, 47,356 subjects were identified. After adjusting for age, gender, and modified Charlson Comorbidity Index score, the utilization of metformin was an independent protecting factor, and the risk of developing lung cancer decreased progressively with either the higher cumulative dose or the higher intensity of metformin use. CONCLUSIONS: This study revealed that the use of metformin decreased the risk of lung cancer in a dose-dependent manner in patients with type 2 DM. The chemo-preventive effect of metformin deserves further study.

Scutellaria barbata inhibits angiogenesis through downregulation of HIF-1 α in lung tumor.

Hypoxia, a hallmark of many solid tumors, is associated with angiogenesis and tumor progression. Hypoxia-inducible factor-1 (HIF-1) plays a significant role in tumor angiogenesis. In this study, the authors constructed a selective platform to screen the traditional Chinese medicine as anti-angiogenic agent. The authors examined the molecular mechanism by which Scutellaria barbata regulates HIF-1-dependent expression of vascular endothelial growth factor (VEGF), which is an important angiogenic factor. Hypoxia promotes angiogenesis by increasing VEGF expression and secretion. Herein, the expression of VEGF was decreased by treatment with S. barbata in tumor cells. Meanwhile, S. barbata reduced the migration and proliferation of endothelial cells under hypoxic condition. S. barbata inhibited the expression of HIF-1α, as well as phosphorylated their upstream signal mediators AKT. S. barbata significantly inhibited the tumor growth in vivo and immunohistochemical studies in the tumors revealed decreased intratumoral microvessel density. These results suggest that the traditional Chinese medicine therapy using S. barbata, which exerts anti-angiogenic activities, represents a promising strategy for the treatment of tumors.