Lipid Profiling Reveals Lipidomic Signatures of Weight Loss Interventions.

Obesity is an epidemic all around the world. Weight loss interventions that are effective differ from each other with regard to various lipidomic responses. Here, we aimed to find lipidomic biomarkers that are related to beneficial changes in weight loss. We adopted an untargeted liquid chromatography with tandem mass spectrometry (LC-MS/MS) method to measure 953 lipid species for Exercise (exercise intervention cohort, N = 25), 1388 lipid species for LSG (laparoscopic sleeve gastrectomy cohort, N = 36), and 886 lipid species for Cushing (surgical removal of the ACTH-secreting pituitary adenomas cohort, N = 25). Overall, the total diacylglycerol (DG), triacylglycerol (TG), phosphatidylethanolamine (PE), phosphatidylinositol (PI), phosphatidylserine (PS), and sphingomyelin (SM) levels were associated with changes in BMI, glycated hemoglobin (HbA1c), triglyceride, and total cholesterol according to weight loss interventions. We found that 73 lipid species changed among the three weight loss interventions. We screened 13 lipid species with better predictive accuracy in diagnosing weight loss situations in either Exercise, LSG, or Cushing cohorts (AUROC > 0.7). More importantly, we identified three phosphatidylcholine (PC) lipid species, PC (14:0_18:3), PC (31:1), and PC (32:2) that were significantly associated with weight change in three studies. Our results highlight potential lipidomic biomarkers that, in the future, could be used in personalized approaches involving weight loss interventions.

Cuproptosis-related lncRNAs predict the prognosis and immune response in hepatocellular carcinoma.

Cuproptosis has been recently used to indicate unique biological processes triggered by Cu action as a new term. This study aimed to explore the relationship between cuproptosis-related lncRNA and hepatocellular carcinoma (HCC) with regard to immunity and prognosis. RNA sequencing and the clinical data were downloaded from the TCGA database. The cuproptosis-related genes were sorted out through literature study. The cuproptosis-related IncRNA signature was identified by Cox regression analysis and the least absolute shrinkage and selection operator analysis. The K-M survival analysis, receiver operating characteristic analysis, and C-index analysis were adopted to evaluate the prognostic prediction performance of the signature. The functional enrichment, immune infiltration and tumor mutation analysis were further analyzed. Subsequently, we predicted the differences in chemosensitivity from tumor gene expression levels for some chemotherapy drugs. The prognostic signature consisting of 5 overall survival-related CUPlncRNAs. It showed an extraordinary ability to predict the prognoses of patients with HCC. The signature can predict the abundance of immune cell infiltration, immune functions, expression of immune checkpoint inhibitors, m6A genes, which was supported by the GO biological process and KEGG analysis. And it may also have a guiding effect in the sensitivity of different chemotherapeutic drugs and tumor mutation burden. We constructed a new cuproptosis-related lncRNA signature for HCC patients. The model can be used for prognostic prediction and immune evaluation, providing a reference for immunotherapies and targeted therapies.

Characteristics of Oral Mucosal Lesions and Their Association With Socioeconomic Status and Systemic Health: A Cross-Sectional Study of Consecutively Collected Oral Medicine Clinic Data in a Remote Rural Area of China.

Objectives: Epidemiological data of oral mucosal lesions (OMLs) are required to develop practical oral care policies. However, limited data are available for rural areas in China. We aimed to estimate the spectrum and frequency of OMLs and to identify their associated socioeconomic status (SES) and systemic health in a remote rural area in Yunnan, China. Methods: We screened patients for OMLs in an oral medicine clinic in rural Yunnan, China, from August 2020 to February 2021. OMLs were documented. SES, including the highest education level achieved and the previous month's household income, as well as the patient's systemic health, including a history of smoking, alcohol use, and chronic disease, were obtained from the Medical History/Health Questionnaire Form and patient medical records. Results: A total of 146 patients were found to have OMLs. The most frequent OML was aphthous ulcer (n = 41, 28.1%), followed by burning mouth syndrome (BMS) (n = 16, 11.0%), viral ulcer (n = 14, 9.6%), and oral lichen planus (OLP) (n = 9, 6.2%). In these patients, the most common chronic diseases were sleep apnea (n = 35, 24.0%), hypertension (n = 23, 15.8%), bronchitis (n = 16, 11.0%), reflux (including gastroesophageal reflux disease) (n = 12, 8.2%), and arthritis (n = 11, 7.5%). On adjusted regression, the patients without chronic diseases had a lower risk of BMS than those with chronic diseases [odds ratio (OR), 0.2; 95% confidence interval (CI), 0.03-0.9]. Age was an independent protective factor for viral ulcers (OR, 1.0; 95% CI, 0.9-1.0). Patients with low-income levels had a lower risk of OLP than those with high-income levels (OR, 0.2; 95% CI, 0.05-0.9). Conclusions: Our oral medicine clinic data in remote Yunnan, China, showed the most frequent OML was aphthous ulcer, which was followed by BMS, viral ulcer, and OLP. Oral care policies should be prioritized among patients with aphthous ulcer. Preventive strategy of BMS should be targeted to people with chronic disease for health equalities. Therefore, an individualized strategy for interventions of OMLs might be optimal, based on the specific epidemiologic characteristics in rural settings.

Proteomics and Organoid Culture Reveal the Underlying Pathogenesis of Hashimoto's Thyroiditis.

Hashimoto's thyroiditis (HT) is an autoimmune disease, and its incidence continues to rise. Although scientists have studied this disease for many years and discovered the potential effects of various proteins in it, the specific pathogenesis is still not fully comprehended. To understand HT and translate this knowledge to clinical applications, we took the mass spectrometric analysis on thyroid tissue fine-needle puncture from HT patients and healthy people in an attempt to make a further understanding of the pathogenesis of HT. A total of 44 proteins with differential expression were identified in HT patients, and these proteins play vital roles in cell adhesion, cell metabolism, and thyroxine synthesis. Combining patient clinical trial sample information, we further compared the transient changes of gene expression regulation in HT and papillary thyroid carcinoma (PTC) samples. More importantly, we developed patient-derived HT and PTC organoids as a promising new preclinical model to verify these potential markers. Our data revealed a marked characteristic of HT organoid in upregulating chemokines that include C-C motif chemokine ligand (CCL) 2 and CCL3, which play a key role in the pathogenesis of HT. Overall, our research has enriched everyone's understanding of the pathogenesis of HT and provides a certain reference for the treatment of the disease.

Risk Factors for Hypothalamic Obesity in Patients With Adult-Onset Craniopharyngioma: A Consecutive Series of 120 Cases.

Context: Hypothalamic obesity (HO) is a severe complication following craniopharyngioma, but studies regarding the sequelae in adult-onset patients with craniopharyngioma are sparse. Objective: The objective of the study was to describe weight changes after surgical treatment in adult-onset craniopharyngioma patients and to analyze risk factors for postoperative weight gain and HO. Subjects and Method: A retrospective analysis was conducted of 120 adult-onset patients who underwent surgery for craniopharyngioma and follow-up at the institution of the authors between January 2018 and September 2020. Clinical characteristics, anthropometric data, image features, treatment modalities, and endocrine indices were collected. Multivariable logistic regression analysis was used to identify independent risk factors for postoperative weight gain and HO. Results: Forty-nine (40.8%) patients had clinically meaningful weight gain (≥5%) in a median follow-up time of 12.0 months (range 1.0-41.0 months) after surgery. The mean postoperative weight gain in this subgroup was 17.59 ± 12.28 (%). Weight gain continued in the first year following surgery. Patients with lower preoperative BMI [OR 0.78, 95% CI (0.67-0.90), P = 0.001] and the adamantinomatous subtype [OR 3.46, 95% CI (1.02-11.76), P = 0.047] were more likely to experience postoperative weight gain ≥5%. The prevalence of HO was 19.2% preoperatively and increased to 29.2% at last follow-up postoperatively. Only preoperative BMI [OR 2.51, 95% CI (1.64-3.85), P < 0.001] was identified as an independent risk factor for postoperative HO. Conclusions: HO is a common complication in patients with adult-onset craniopharyngioma. Patients with higher preoperative BMI had a greater risk for developing HO postoperatively.

Efficacy and Safety of Aspirin Combined with Low-Dose P2Y12 Receptor Antagonists in East Asian Patients Undergoing PCI.

Previous studies have indicated that low-dose new generation of P2Y12 receptor antagonists may be more suitable compared with clopidogrel at a standard dose for the dual antiplatelet therapy (DAPT) for East Asian patients receiving percutaneous coronary intervention (PCI). However, there remains no consensus in clinical practice. Thus, in this study, we aimed to determine the efficacy and safety of low-dose P2Y12 receptor antagonists, compared to clopidogrel at a standard dose, in DAPT in East Asian patients after PCI. We systematically searched literatures for randomized controlled trials (RCT) comparing low-dose P2Y12 receptor antagonists with standard-dose clopidogrel for the treatment of East Asian patients undergoing PCI. The endpoints of efficacy include major adverse cardiac events (MACEs), all-cause mortality, and the number of target vessel revascularization. The indicators of safety include major and minor bleeding events. Heterogeneity was evaluated by I2 statistic test. Begg's and Egger's tests were used to evaluate publication bias. In total, 2,747 subjects from 8 RCT studies were included. Low-dose new P2Y12 receptor antagonists, that is, ticagrelor or prasugrel, showed significantly lower incidence of MACEs, as compared with standard-dose clopidogrel, in the East Asian patients who are in DAPT after undergoing PCI. Further, no difference was noted for the risk of major and minor bleeding events. In East Asian patients undergoing PCI and receiving DAPT, the use of low-dose P2Y12 receptor antagonists, ticagrelor or prasugrel, has been determined to be superior than clopidogrel at standard dose; this has been evidenced by a lower incidence of MACEs without increasing the risk of bleeding.

Combination therapy with afatinib and bevacizumab in an EGFR-mutated non-small cell lung cancer patient with acquired ERBB2 amplification: A case report.

INTRODUCTION: Acquired resistance to reversible EGFR tyrosine kinase inhibitors remains a significant obstacle, and acquired ERBB2 amplification is the most common "bypass" mechanism. For patients with sensitizing EGFR mutation who experience resistance via ERBB2 amplification, no targeted drug has been demonstrated to be effective. PATIENT CONCERNS: A 56-year-old female nonsmoker suffered from left leg paralysis and low back pain. Imaging examination revealed a mass in the anterior segment of the right upper lobe lung and possible multiple metastases in the right hilar, mediastinal lymph nodes, bone metastases, and soft tissue invasion. DIAGNOSIS: Transbronchial lung biopsy revealed a moderately differentiated adenocarcinoma (cT4N2M1c, stage IV). An EGFR exon 19 deletion was identified using amplification refractory mutation system. INTERVENTIONS: After the patient was treated with gefitinib initiation (250 mg/d) for 15 months, the tumor progressed with ERBB2 amplification revealed by next-generation sequencing test. Then, the patient was started on afatinib (40 mg/d) plus bevacizumab (7.5 mg/kg every 3 weeks). OUTCOMES: The combination therapy of afatinib and bevacizumab in this patient was effective with some slight side effects. Computed tomography scans showed the tumor shrinkage and the pleural effusion disappeared in the right lung. The overall survival was 23.5 months. CONCLUSION: To date, there is no targeted therapy approved and demonstrated to be effective for non-small cell lung cancer patients with EGFR sensitizing mutations, and ERBB2 amplification. The effectiveness of combination therapy with afatinib and bevacizumab may provide a new therapeutic option for these patients.

Posterior percutaneous endoscopic lumbar discectomy combined with the vertical anchoring technique for lumbar disc herniation with distant upward migration.

BACKGROUND: Posterior percutaneous endoscopic lumbar discectomy (PELD) has become a preferred procedure for the treatment of simple lumbar disc herniation (LDH) but has rarely been reported for distant upward migration. The purpose of this research was to investigate the feasibility, safety, clinical efficacy and technical points of posterior PELD combined with the vertical anchoring technique (VAT) for the treatment of LDH with distant upward migration. METHODS: Thirteen patients with distant upward migrated LDH who underwent posterior PELD combined with the VAT from March 2016 to May 2018 were selected. Among these cases, the herniated disc was located at L3/4 in 2 patients, L4/5 in 9 patients and L5/S1 in 2 patients. The operative time, length of hospital stay and postoperative complications were recorded. The visual analogue score (VAS), Oswestry Disability Index (ODI), Japanese Orthopaedic Association (JOA) scores and modified MacNab criteria were used to assess surgical efficacy. RESULTS: All 13 patients underwent successful surgery. We compared the VAS, ODI and JOA scores before and after surgery. The differences were statistically significant (P < 0.05). According to the modified MacNab criteria, 10 patients were assessed as "excellent", 2 patients were assessed as "good" and 1 patient was assessed as "fair" at the last follow-up. The rate of satisfactory outcomes was 92.3%. CONCLUSION: Posterior PELD combined with the VAT is a safe and feasible procedure for the treatment of LDH with distant upward migration and represents a new approach for this type of surgery.

[Effects of inhibitory concentration minocycline on the proliferation, differentiation, and mineralization of osteoblasts].

OBJECTIVE: To study the effect of the inhibitory concentration minocycline on the proliferation, differentiation, and expression of Runt-related transcription factor 2 (Runx2), alkaline phosphatase (ALP) and osteopontin (OPN) mRNA of osteoblasts. METHODS: Primary osteoblasts were cultured in osteogenic induction medium containing 0, 0.1, 0.5, 1, 10 µg·mL⁻¹ minocycline. Cell counting kit-8 was used to observe cell proliferation. ALP activity assay, alizarin red S staining, and real-time quantitative polymerase chain reaction (PCR) were used to determine cell differentiation and mineralization. RESULTS: The groups with 0.1, 0.5, 1 µg·mL⁻¹ minocycline promoted cell proliferation. The mRNA expression levels of ALP and Runx2 were up-regulated. Osteoblast-mediated mineralization was increased. The group with 1 µg·mL⁻¹ showed maximal promotion effect (P<0.05). When the concentration increased to 10 µg·mL⁻¹, the promoting effect began to decline, and the ALP activity and OPN expression were significantly inhibited (P<0.01). CONCLUSIONS: Appropriate concentration of minocycline can promote osteoblasts proliferation, up-regulate the expression levels of Runx2, ALP and OPN, and increase the differentiation and mineralization of osteoblasts.

PKA-RIIB Deficiency Induces Brown Fatlike Adipocytes in Inguinal WAT and Promotes Energy Expenditure in Male FVB/NJ Mice.

Obesity has become the most common metabolic disorder worldwide. Promoting brown adipose tissue (BAT) and beige adipose tissue formation, and therefore, a functional increase in energy expenditure, may counteract obesity. Mice lacking type IIß regulatory subunit of adenosine 3',5' cyclic monophosphate (cAMP)-dependent protein kinase A (PKA-RIIB) display reduced adiposity and resistance to diet-induced obesity. PKA-RIIB, encoded by the Prkar2b gene, is most abundant in BAT and white adipose tissue (WAT) and in the brain. In this study, we show that mice lacking PKA-RIIB have increased energy expenditure, limited weight gain, and improved glucose metabolism. PKA-RIIB deficiency induces brownlike adipocyte in inguinal WAT (iWAT). PKA-RIIB deficiency also increases the expression of uncoupling protein 1 and other thermogenic genes in iWAT and primary preadipocytes from iWAT through a mechanism involving increased PKA activity, which is represented by increased phosphorylation of PKA substrate, cAMP response element binding protein, and P38 mitogen-activated protein kinase. Our study provides evidence for the role of PKA-RIIB deficiency in regulating thermogenesis in WAT, which may potentially have therapeutic implications for the treatment of obesity and related metabolic disorders.

Recovery of HPA Axis Function After Successful Gonadotropin-Induced Pregnancy and Delivery in a Woman With Panhypopituitarism: Case Report and Review.

Hypopituitarism is defined as the partial or complete defect of anterior pituitary hormone secretion. Patients with hypopituitarism usually need life-long hormone replacement therapy. However, in this case, we report a patient with panhypopituitarism whose hypothalamus-pituitary-adrenal (HPA) axis function was completely recovered after pregnancy and delivery. In this case study, we reported the case management and conducted a review of literature to identify the possible mechanism of pituitary function recovery. The patient who suffered from secondary amenorrhea was found a nonfunctioning pituitary macroadenoma, and the hormone test showed serum cortisol, FT3, FT4, thyrotropic hormone, and prolactin were at normal range. After surgical removal of the tumor which invasion in the sellar region, the patient had panhypopituitarism confirmed by the routine hormone test. Though spontaneous pregnancy is impossible in female patients with panhypopituitarism, the patient was restored fertility by the help of artificial reproductive techniques. After the confirmation of the pregnancy, levothyroixine was increased to 75 µg daily and readjusted to 150 µg daily before delivery according to the monthly measurement thyroid function. Hydrocortisone 10 mg daily replaced cortisone acetate; the dose was increased according to the symptoms of morning sickness. A single stress dose of hydrocortisone (200 mg) was used before elective cesarean delivery and was tapered to the dose of 10 mg per day in 1 week. Levothyroixine was reduced to 75 µg daily after delivery. During follow-up, her hypothalamus-pituitary-adrenal (HPA) axis function was completely recovered. The peak serum cortisol level could increase to 19.08 µg/dL by insulin-induced hypoglycemia. However, growth hormone remained unresponsive to the insulin-tolerance test, and thyroid hormone still needed exogenous supplementation. Hormone replacement therapy needed closely followed by endocrinologist and multidisciplinary cooperation during the pregnancy of patients with hypopituitarism. This case indicates that the pituitary function may partially recover after pregnancy in panhypopituitarism patients.

Incidence of Pituitary Apoplexy and Its Risk Factors in Chinese People: A Database Study of Patients with Pituitary Adenoma.

BACKGROUND: There are few studies of the incidence and clinical characteristics of pituitary apoplexy (PA) in pituitary adenoma patients, and the findings have been inconsistent. OBJECTIVE: The aim of the study was to retrospectively assess the incidence, clinical presentation, surgical management and postoperative complications of PA in pituitary adenoma patients. METHODS: A database was specifically designed to collect clinical, therapeutic, prognostic and histological information about pituitary adenoma patients. Using multivariate logistic regression, odds ratios (ORs) with 95% confidence intervals (CIs) were calculated to identify associated factors. RESULTS: A total of 2021 pituitary adenoma patients were recruited. 97 (4.8%) patients had PA. The incidence of PA was 10.11% in patients with pituitary macroadenoma, and 0.36% in patients with microadenoma. Variables for the logistic regression model independently associated with PA were sex (male vs. female, OR = 2.54, 95% CI: 1.59~4.07), tumor type (negative staining vs. positive staining, OR = 2.04, 95% CI: 1.29~3.23), and tumor size (macroadenoma vs. microadenoma, OR = 26.46, 95% CI = 9.66~72.46). Headache, visual deterioration, and vomiting were the most common symptoms in patients with pituitary adenoma. Patients with and without PA had similar frequency of visual deterioration, head trauma, acromegalic appearance, galactorrhoea, cold intolerance and Cushingoid appearance, but headache, vomiting, ptosis, diplopia, fever and blindness were significantly more common in patients with PA. Pearson Chi-Square tests revealed a significant difference in surgical approach between patients with and without PA (95.88% vs. 85.57%, P = 0.01). CONCLUSION: Our findings suggest that PA is not a rare event. Male sex, non-functioning tumor, and macroadenoma are associated with an increased risk of PA. Compared with pituitary adenoma patients without PA, patients with PA have more severe symptoms.

The effect of neuropeptide Y on brown-like adipocyte's differentiation and activation.

Despite its wide distribution in the central nervous system, the presence of Neuropeptide Y (NPY) in peripheral tissues has been detected. White adipose tissue (WAT) is a new site of NPY synthesis and secretion. The development of brown-like adipocytes in WAT is controlled by hypothalamic NPY neurons through interaction with sympathetic nervous system (SNS). However, whether peripheral NPY has a direct effect on induction of the Uncoupling protein1 (UCP1)-positive adipocytes is unknown. We have used adipocytes derived from C3H10T1/2 stem cells as a model of brown-like adipocyte, and investigated the role of NPY in their differentiation and activation. In general, NPY had no effect on brown adipogenesis of C3H10T1/2 stem cell, but suppressed db-cAMP activation of brown-like adipocytes, which was due to blunting brown fat-relevant gene expression and mitochondrial function. NPY showed suppression in a receptor-dependent manner, inhibition of endogenous cAMP production and cAMP-PKA-dependent pathways p38 MAPK and CREB phosphorylation were involved in the downstream mechanisms. A novel role of NPY in the peripheral is presented, which may help decrease energy expenditure in WAT of obese subjects.

The prevalence and predictors of active brown adipose tissue in Chinese adults.

OBJECTIVE: Previous studies have shown that active brown adipose tissue (BAT) is present in adults and may play important roles in the regulation of energy homeostasis. However, nearly every study has been carried out in patients undergoing scanning for cancer surveillance (CS), whose metabolism and BAT activity may not reflect those of healthy individuals. The objective of this study was to investigate the prevalence and predictors of active BAT in Chinese adults, particularly in healthy individuals. DESIGN: A total of 31,088 consecutive subjects aged ≥18 years who had undergone positron emission tomography/computed tomography (PET/CT) scanning of BAT were evaluated in this study. METHODS: We measured BAT activity via (18)F-fluorodeoxyglucose PET/CT in subjects who had undergone scanning for either a routine medical checkup (MC) or CS in Shanghai. Then, we investigated the predictors of active BAT, particularly in healthy individuals. RESULTS: In both groups, the prevalence of BAT was higher in women than in men. Using a multivariate logistic analysis, we found age, sex, BMI, and high thyroid glucose uptake to be significant predictors of BAT activity in the MC group. Similarly, we found age, sex, and BMI to be significant predictors of BAT activity, but not thyroid high glucose uptake, in the CS group. CONCLUSIONS: In Chinese adults, BAT activity inversely correlates with BMI and thyroid high glucose uptake, which reinforces the central role of brown fat in adult metabolism and provides clues to a potential means for treating the metabolic syndrome.

Differences in the metabolic status of healthy adults with and without active brown adipose tissue.

BACKGROUND: Previous studies have proven the existence of active brown adipose tissue (BAT) in adults; however, its effect on systematic metabolism remains unclear. AIM: The current study was designed to investigate the differences in the metabolic profiles of healthy adults with and without active BAT using positron emission tomography-computed tomography (PET-CT) scans in the un-stimulated state. METHODS: A cross-sectional analysis was performed to assess the health of adults using PET-CT whole-body scans at Huashan Hospital Medical Centre between November 2009 and May 2010. A total of 62 healthy adults with active BAT were enrolled in the BAT-positive group. For each positive subject, a same-gender individual who underwent PET-CT the same day and who had no detectable BAT was chosen as the negative control. Body composition was measured, and blood samples were collected for assays of metabolic profiles and other biomarkers. RESULTS: In both the male and female groups, BAT-positive individuals were younger and had lower body mass indexes, fasting insulin, insulin resistance, and leptin, but a greater level of high-density lipoprotein cholesterol compared with the negative controls. In the male group, body fat content and levels of tumor necrosis factor-α were significantly lower in the BAT-positive than in the negative control group. CONCLUSIONS: The healthy adults with active BAT in an un-stimulated state had favorable metabolic profiles suggesting that active BAT may be a potential target for preventing and treating obesity and other metabolic disorders.