Integrating machine learning algorithms and multiple immunohistochemistry validation to unveil novel diagnostic markers based on costimulatory molecules for predicting immune microenvironment status in triple-negative breast cancer.

Introduction: Costimulatory molecules are putative novel targets or potential additions to current available immunotherapy, but their expression patterns and clinical value in triple-negative breast cancer (TNBC) are to be clarified. Methods: The gene expression profiles datasets of TNBC patients were obtained from The Cancer Genome Atlas and the Gene Expression Omnibus databases. Diagnostic biomarkers for stratifying individualized tumor immune microenvironment (TIME) were identified using the Least Absolute Shrinkage and Selection Operator (LASSO) and Support Vector Machine-Recursive Feature Elimination (SVM-RFE) algorithms. Additionally, we explored their associations with response to immunotherapy via the multiplex immunohistochemistry (mIHC). Results: A total of 60 costimulatory molecule genes (CMGs) were obtained, and we determined two different TIME subclasses ("hot" and "cold") through the K-means clustering method. The "hot" tumors presented a higher infiltration of activated immune cells, i.e., CD4 memory-activated T cells, resting NK cells, M1 macrophages, and CD8 T cells, thereby enriched in the B cell and T cell receptor signaling pathways. LASSO and SVM-RFE algorithms identified three CMGs (CD86, TNFRSF17 and TNFRSF1B) as diagnostic biomarkers. Following, a novel diagnostic nomogram was constructed for predicting individualized TIME status and was validated with good predictive accuracy in TCGA, GSE76250 and GSE58812 databases. Further mIHC conformed that TNBC patients with high CD86, TNFRSF17 and TNFRSF1B levels tended to respond to immunotherapy. Conclusion: This study supplemented evidence about the value of CMGs in TNBC. In addition, CD86, TNFRSF17 and TNFRSF1B were found as potential biomarkers, significantly promoting TNBC patient selection for immunotherapeutic guidance.

Headache alleviation with nasal irrigation following endoscopic endonasal surgery for pituitary adenomas.

BACKGROUND: Headache is a common occurrence after endoscopic endonasal surgery (EES) for pituitary adenomas and significantly impacts the quality of life of patients. This study aims to investigate the effectiveness of nasal irrigation in relieving postoperative headache after EES. METHODS: A retrospective analysis was conducted on a cohort of 101 patients (Cohort I) who underwent EES for pituitary adenomas to explore the risk factors associated with postoperative headache. Another cohort of 72 patients (Cohort II) who received adjuvant nasal irrigation following surgery was enrolled for further analysis. The Headache Impact Test (HIT-6) was used to score the severity of headache, and patients with a HIT score > 55 were classified as having headache. RESULTS: In Cohort I, 21.78% of patients experienced headache one month after EES, which decreased to 5.94% at the three-month follow-up. Multivariate analysis revealed that postoperative nasal sinusitis (OR = 3.88, 95%CI 1.16-13.03, p = 0.028) and Hardy's grade C-D (OR = 10.53, 95%CI 1.02-109.19, p = 0.049) independently predicted the presence of postoperative headache at one month. At the three-month follow-up, patients with sinusitis had higher HIT-6 scores compared to those without sinusitis (44.43 ± 9.78 vs. 39.72 ± 5.25, p = 0.017). In Cohort II, the incidence of sinusitis at three months was significantly lower than that in Cohort I (p = 0.028). Importantly, both the incidence of headache and HIT-6 scores in Cohort II were significantly lower than those in Cohort I at the one- and three-month follow-ups. CONCLUSIONS: Postoperative sinusitis is an independent risk factor for the development of headache following EES for pituitary adenomas. Prophylactic nasal irrigation helps relieve postoperative headache, possibly by preventing the occurrence of sinusitis.

Integrated pyroptosis measurement and metabolomics to elucidate the effect and mechanism of tangzhiqing on atherosclerosis.

Tangzhiqing formula (TZQ) is a traditional Chinese medicine prescribed to treat glucose and lipid metabolism disorders. A significant effect of TZQ on diabetes and hyperlipidemia has been demonstrated, but its effect on atherosclerosis (AS) remains unknown. This study combines pyroptosis with metabolomics to elucidate the effect and mechanism of TZQ on AS. A model of AS was developed using ApoE-/- mice fed a high-fat diet for 8 weeks. After 6 weeks of atorvastatin (Ator) or TZQ treatment, aortic lumen diameter, aortic lesion size, serum lipid profile, cytokines, and Nod-like receptor protein 3 (NLRP3) inflammasome-mediated pyroptosis were analyzed. Serum metabolomics profiles were obtained to examine the effect of TZQ on AS and the correlation between pyroptosis and metabolites was further analyzed. As a result, TZQ significantly reduced the diameter of the common carotid artery during diastole and the blood flow velocity in the aorta during systole; reduced blood lipid levels, arterial vascular plaques, and the release of inflammatory cytokines; and inhibited the NLRP3 inflammasome-mediated pyroptosis. According to metabolomics profiling, TZQ is engaged in the treatment of AS via altering arachidonic acid metabolism, glycerophospholipid metabolism, steroid hormone production, and unsaturated fatty acid biosynthesis. The cytochrome P450 enzyme family and cyclooxygenase 2 (COX-2) are two major metabolic enzymes associated with pyroptosis.

Management of dermatologic adverse events associated with tumor treating fields in patients with glioblastoma multiforme: A 27-case series.

Objective: This study summarized the clinical management of 27 patients with glioblastoma multiforme who tumor treating fields therapy for the healthcare providers. Methods: Glioblastoma multiforme patients who experienced dermatologic adverse events after tumor treating fields therapy from April 2019 to May 2021 were included. The clinical management involved educating patients and their caregivers on the prevention of dermatologic adverse events, scalp assessment and preparation, and removal and replacement of the transducer array. Informed consent for participating in the study including the taking of pictures was obtained from all patients. Results: The dermatologic adverse events were successfully managed in all 27 patients, with no severe dermatologic adverse events were reported. Conclusions: Data on tumor treating fields-related dermatologic adverse events is rarely reported, and published reports of management of scalp dermatologic adverse events are lacking. This case series summarizes a clinically individualized management for tumor treating fields-related dermatologic adverse events.

Incidence, trend and risk factors associated with suicide among patients with malignant intracranial tumors: a surveillance, epidemiology, and end results analysis.

BACKGROUND: Cancer patients are associated with an elevated risk of suicide. This study aims to investigate the suicide rates and identify risk factors for suicide among patients with malignant intracranial tumors (MITs). METHODS: Patients diagnosed with MITs during the years of 1975-2015 were identified from the Surveillance, Epidemiology, and End Results (SEER) program. Suicide rates and standardized mortality ratios (SMR) were calculated. Cox regression analyses were used to identified risk factors for suicide among MIT patients. RESULTS: Among 115,668 patients with MITs collected from the SEER program, 99 committed suicide. The rate of suicide was 23.02 per 100,000 person-years, and SMR of suicide was 1.90. Diagnosis in recent era (years 2000-2015, SMR = 2.01), male gender (SMR = 1.78), older age (60-79 years, SMR = 3.54), white race (SMR = 1.86), married persons (SMR = 2.31), living in rural areas (SMR = 2.50), history of other malignancy (SMR = 3.81), diagnosis of glioblastoma (SMR = 4.05) and supratentorial location (SMR = 2.45) were associated with an increased incidence of suicide. In addition, the risk of suicide increased significantly within the first year after diagnosis (SMR = 13.04). Multivariate Cox regressions showed that older age, male sex, and supratentorial location were independent risk factors for suicide. CONCLUSIONS: The suicide mortality among patients with MITs steadily elevated in the past decades. Male sex, older age, and supratentorial location were significantly associated with risk of suicide, especially within the first year following diagnosis. Healthcare providers should early identify and effectively intervene with MIT patients at risk.

The application of fluorescein sodium for the resection of medulloblastoma.

INTRODUCTION: Surgical resection of medulloblastoma (MB) remains a challenge. At present, a variety of tracers have been used for intraoperative tumor visualization. However, there are few reports on the intraoperative visualization of MB. Hence, we reported our experience of applying fluorescein sodium (FS) in MB surgery. METHODS: We retrospectively analyzed the clinical information of patients with MB confirmed by surgery and pathology from January 2016 to December 2020 from Sun Yat-sen University Cancer Center. A total of 62 patients were enrolled, of which 27 received intraoperative FS and 35 did not. The intraoperative dose of FS was 3 mg/kg. RESULTS: Among the 62 patients, 42 were males, and twenty were females. The age of onset in the FS group was 9.588 ± 7.322, which in the non-fluorescein sodium group was 13.469 ± 10.968, p = 0.198. We did not find significant differences in tumor location, tumor size, tumor resection, tumor histology, and preoperative symptoms (hydrocephalus, headache, vomit, balance disorder) between the groups. There was no significant difference in the postoperative symptoms (hydrocephalus, headache, vomiting, balance disorder, and cerebellar mutism). However, patients in the FS group had a relatively low incidence of balance disorder and cerebellar mutism. There was definite fluorescence of tumor in all cases of the FS group, and even the tiny metastatic lesion was visible. No case had side effects related to the use of FS. CONCLUSIONS: FS is safe and effective in MB surgery. Whether the application of FS for surgery can reduce complications remains to be studied in the future.

Factors Associated with Behaviors Toward End-of-life Care Among Chinese Oncology Nurses: A Cross-Sectional Study.

PURPOSE: The goal of this study was to describe the current status of oncology nurses' behaviors toward end of life (EOL) care in China and to explore the factors associated with oncology nurses' behaviors toward EOL care. METHODS: A cross-sectional design was applied and a convenience sample of 1038 oncology nurses from 22 grade A hospitals were recruited into this study. A general social demographic data questionnaire was administered, and the Chinese version of Nurses' Behaviors of Caring for Dying Patients Scale was used to assess nurse behavior toward EOL care. The total score ranges from 40 to 200 points. Data were analyzed with SPSS 26.0 software. RESULTS: Chinese oncology nurses' average score of holistic EOL care behaviors was 2.97 ± 0.59. Oncology nurses provide physical care most (3.81 ± 0.76), followed by family care (3.02 ± 0.86), and spiritual care (2.37 ± 0.67). Multiple regression analysis showed that a higher frequency of sharing EOL care experience with colleagues, in-service palliative care education, higher level of head nurse support for EOL patient care, more cases of EOL care, higher working position, and nurse's perceived high level of support were positively associated with behavior toward EOL care. These six factors explained 16.2% of the total variance. CONCLUSIONS: The results may help provide a basis for converting behavior for EOL care among oncology nurses and design interventions to better improve quality of life for EOL patients with cancer in China.

Risk factors for postoperative cerebrospinal fluid leakage after transsphenoidal surgery for pituitary adenoma: a meta-analysis and systematic review.

OBJECTIVE: Postoperative cerebrospinal fluid (CSF) leakage represents a challenge even for experienced pituitary surgeons. We aimed to quantitatively synthesize data from studies regarding the risk factors for postoperative CSF leakage after transsphenoidal surgery (TSS) for pituitary adenoma (PA). METHODS: PubMed, Web of Science, The Cochrane Library, Embase, China National Knowledge Infrastructure (CNKI), Wanfang database, and VIP database were searched for case-control and cohort studies, focusing on the risk factors associated with postoperative CSF leakage after TSS for PA. Pooled odds ratios (ORs) and 95% confidence intervals were calculated to determine the risk factors. RESULTS: A total of 34 case-control and cohort studies involving a total of 9,144 patients with PA were included in this systematic review. The overall rate of postoperative CSF leakage after TSS for PA was 5.6%. Tumor size, adenoma consistency, revision surgery, and intraoperative CSF leakage were independent risk factors for postoperative CSF leakage (ORs, 3.18-6.33). By contrast, the endoscopic approach showed a slight protective benefit compared with the microscopic approach in TSS (OR, 0.69). CONCLUSIONS: This review provides a comprehensive overview of the quality of the evidence base, informing clinical staff of the importance of screening risk factors for postoperative CSF leakage after TSS for PA. More attention should be paid to PA patients at high risk for CSF leakage after TSS to reduce complications and improve prognosis.

High preoperative albumin-bilirubin score predicts poor survival in patients with newly diagnosed high-grade gliomas.

OBJECTIVE: To determine the prognostic value of the preoperative Albumin-bilirubin (ALBI) score in high-grade glioma (HGG) patients. METHODS: A retrospective study of 194 HGG patients was conducted. ROC analysis was used to determine the optimal cut-off value of ALBI score. Univariate and multivariate analysis was performed to identify prognostic factors associated with progression free survival (PFS) and overall survival (OS). The resulting prognostic models were externally validated by a demographic-matched cohort of 130 HGG patients. RESULTS: Optimal cutoff value of ALBI score was -2.941. In training set, ALBI was correlated with age (P = 0.001), tumor location (P = 0.012) and adjuvant therapy (P = 0.016). Both PFS (8.27 vs. 18.40 months, P<0.001) and OS (13.93 vs. 27.57 months, P<0.001) were significantly worse in the ALBI-high group. Strikingly, patients in ALBI-low group had 56% decrease in the risk of tumor progression and 57% decrease in the risk of death relative to high ALBI. Multivariate analysis further identified ALBI score as an independent predictor for both PFS (HR=0.47, 95% CI 0.34, 0.66) and OS (HR=0.45, 95% CI 0.32, 0.63). The ALBI score remained independent prognostic value in the validation set for both PFS (P = 0.01) and OS (P = 0.007). Patients with low ALBI score had better PFS and OS in all subgroups by tumor grade and treatment modalities. CONCLUSIONS: The preoperative ALBI score is a noninvasive and valuable prognostic marker for HGG patients.

Clinical serum metabolomics study on fluoxetine hydrochloride for depression.

BACKGROUND: Fluoxetine hydrochloride is one of the familiar antidepressants of the second generation and has the effect of inhibiting the reuptake of 5-hydroxytryptamine by central nervous system. Both clinical trials and animal experiments show that it has good antidepressant effect, but there are few reports on its clinical efficacy in treating depression patients from the perspective of metabolomics. This study aimed at evaluating the antidepressant effect of fluoxetine hydrochloride by metabolomics, so that to find out its specific biomarkers and related metabolic characteristics of depression in the treatment of depression and analyze the intervention mechanism of fluoxetine hydrochloride in depression. METHOD: Twenty depression patients and twenty healthy volunteers were recruited in clinical. Using ultra-performance liquid chromatography quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MS) to analyze serum metabolites of depression patients pretherapy and post-treatment and compared with healthy people. RESULT: Finally, we have detected 16 specific biomarkers of depression. Compared with the healthy group, the level of 10 biomarkers in the depression group was significantly increased (P < 0.05) and 6 biomarkers were significantly decreased (P < 0.01). After 8 weeks of fluoxetine hydrochloride treatment, all the biomarkers have showed a tendency of callback. The metabolic pathways involved amino acid metabolism, energy metabolism and lipid metabolism. CONCLUSION: In our study, the antidepressant effect of fluoxetine hydrochloride in clinic was proved by metabolomics and provided basis for clinical use of fluoxetine hydrochloride. At the same time, the biomarkers that may be related to the occurrence of depression are determined to provide objective basis for the diagnosis of depression.

Clinical Studies on the Treatment of Novel Coronavirus Pneumonia With Traditional Chinese Medicine-A Literature Analysis.

OBJECTIVE: This study aims to analyze the current situation and characteristics of traditional Chinese medicine for treatment of novel coronavirus pneumonia, clarify its clinical advantages and provide a reference for clinical treatment. METHODS: Clinical randomized controlled trials, clinical control trials and case series research involving the use of Chinese medicine for novel coronavirus pneumonia treatment were selected from PubMed, Chinese Journal Service Platform of CNKI, VIP, and WanFang Data Knowledge Service Platform from the establishment of the library to 11:00 am on April 15, 2020. The published information, research design, intervention measures and research observation index were statistically analyzed. RESULTS: Twenty studies were included. The research methods were mainly clinical controlled trials. The observation indicators were mostly fever improvement time, cough improvement time, shortness of breath improvement time, chest CT and CRP examination. Maxing Ganshi (Ephedrae Herba, Armeniacae Semen Amarum, Glycyrrhizae Radix Et Rhizoma, and Gypsum Fibrosum) decoction was the core prescription. The most frequently used drugs were Glycyrrhizae Radix Et Rhizoma (Gancao), Ephedrae Herba (Mahuang), Armeniacae Semen Amarum (Kuxingren), Atractylodis Rhizoma (Cangzhu), and Scutellariae Radix (Huangqin). The most frequently used drug combination was Ephedrae Herba (Mahuang)-Armeniacae Semen Amarum (Kuxingren). The most frequently used Chinese patent medicine was Lianhua Qingwen capsule/granule. CONCLUSIONS: Traditional Chinese medicine has widely used for novel coronavirus pneumonia in China. It is worthy of global attention. Also, high-quality randomized controlled clinical trials on the effectiveness and safety of traditional Chinese medicine in the treatment of novel coronavirus pneumonia need to carry out.

Study of efficacy and safety of Jiaotai pill in the treatment of depression.

BACKGROUND: Depression is a common affective disorder characterized by marked and lasting melancholia, with corresponding thought and behavior changes. Due to an accelerated pace of life and increased work pressure, the incidence of depression has risen sharply, causing great harm to family and social life. Jiaotai pill (JTP) is a Chinese herbal formula that is commonly prescribed for depression and insomnia in clinical treatment, and exhibits antidepressant effects as shown in animal experimental research. However, there are no standard clinical trials to confirm its efficacy in treating depression. OBJECTIVE: This study aims to assess the efficacy and safety of JTP in the treatment of depression, so as to tap the clinical efficacy advantages of JTP and provide data support for its clinical application. METHODS: A randomized, multicenter clinical trial with parallel groups was designed in this study. A total of 40 patients with depression were included and randomly divided to either the treatment or the control group with a ratio of 1:1. The patients received JTP plus fluoxetine or fluoxetine alone once per day for 8 weeks. The primary outcome included the Hamilton Depression Rating Scale score for patients and brain structure and function by functional magnetic resonance imaging. The secondary outcomes included Traditional Chinese medicine syndrome integral scale scores, Wisconsin Card Sorting Test, blood metabonomics, urine metabonomics. CONCLUSION: The results of this trial will find changes in brain structure, brain function, and metabolism in patients with depression, and provide critical evidence for JTP in the treatment of depression.

Clinical practice of Chinese medicine navel therapy for chronic diarrhea: A literature review.

Chronic diarrhea is one of the most common complaints in clinical practice for both adults and children. The purpose of this study was to assess the commonly used Chinese herbal medicine navel therapy for the treatment of chronic diarrhea (traditional Chinese medicine syndrome of spleen deficiency). The literature search was up to June 2018. Four types of studies (clinical trials, case series, case reports, and experts' experience) researched on Chinese medicine navel therapy used alone or combined with other therapies for the treatment of chronic diarrhea all included. Information on prescriptions, effectiveness, and safety of intervention was collected. Traditional Chinese Medicine Inheritance Support System V2.5 was used to do data analysis. We included 416 studies. All these studies carried out in 194 cities of China. We obtained the most commonly used single herbs, herbal medicine combination, and Chinese patent medicine for both adults and children. The top 3 single herbs were Caryophylli Flos (Dingxiang), Cinnamomi Cortex (Rougui), and Euodiae Fructus (Wuzhuyu). The most frequently used Chinese patent medicines were Ding Gui Infantile Navel Paste and Huoxiang Zhengqi Liquid. The effectiveness assessment was based on clinical trials, but we did not perform a meta-analysis because of different study design and unsatisfactory methodological quality. No serious adverse reaction happened in original studies. The application of Chinese medicine navel therapy could be one of the ideal treatments for chronic diarrhea in the future, especially for children. However, high-quality studies are very needed to provide clear evidence.

Surgical Resection of Pineal Epidermoid Cyst Contributed to Relieving Schizophrenia Symptoms.

BACKGROUND: The pineal gland has been demonstrated to be involved in the development of mood and psychotic disorders. However, few studies have looked at the relationship between pineal region tumors and psychiatric disorders. Intracranial epidermoid cysts usually arise in the cerebellopontine angle area and are extremely rare in the pineal region. The case of pineal epidermoid cyst presenting as schizophrenia has never been reported before. CASE PRESENTATION: We described the case of a 23-year-old man who presented to the hospital with symptoms suggestive of schizophrenia. During work-up, he was found to have a pineal lesion on brain magnetic resonance imaging. Total resection of the tumor was subsequently performed, and pathology confirmed an epidermoid cyst. One month after surgery, the patient's psychotic symptoms significantly improved free of drug and fully returned to work 3 months postoperatively. CONCLUSIONS: This case highlights the importance of including mass lesions of the pineal region in the differential diagnosis of psychotic disorders. It also provides further support that the pineal region may play a role in the pathophysiology of psychiatric diseases, although more studies will be needed to elucidate this interesting connection.

Practice of Comparative Effectiveness Research to Identify Treatment Characteristics of Similar Chinese Patent Medicine for Angina Pectoris.

OBJECTIVE: Individualized application of TCM is not easy and may lead to undesirable results, such as poor effect or even adverse reactions. This trial aims to compare two common Chinese patent medicines with similar effects. BACKGROUND OF THE RESEARCH: Four hospitals carried out the test at the same time in Tianjin city of China. PARTICIPANTS: 144 patients were involved in this study; all patients must meet the diagnostic criteria. INTERVENTIONS: Qishen Yiqi pills, compound danshen pills, and their placebos; an efficacy analysis was conducted after the first medication and after crossover medication. PRIMARY OUTCOME MEASURES: The primary index of end point includes Seattle Angina Questionnaire score-7 and score of 7-point Likert Scale; the curative effect was compared with minimal clinically important differences value. RESULT: Two drugs have their respective advantages in treating SAP. In practical application, the two drugs shall be discriminated in use based on patients' specific symptoms. TRIAL REGISTRATION: Chinese clinical trials register is ChiCTR-TTRCC-14004406 (registered 23 March 2014).