Apoptosis in glaucoma: A new direction for the treatment of glaucoma (Review).

Glaucoma is a group of progressive optic nerve disorders characterized by the loss of retinal ganglion cells, a thinner retinal nerve fibre layer and cupping of the optic disk. Apoptosis is a physiological cell death process regulated by genes and plays a crucial role in maintaining tissue homeostasis, ensuring the natural development and immune defence of organisms. Apoptosis has been associated with glaucoma and inhibiting apoptosis by activating phosphatidylinositol 3-kinase­protein kinase B or other medicines can rescue pathological changes in glaucoma. Due to the complex crosstalk of apoptosis pathways, the pathophysiological mechanism of apoptosis in glaucoma needs to be fully elucidated. The present review aimed to discuss the mechanism of cell apoptosis in glaucoma, improve the understanding of the pathophysiology of glaucoma, summarize new directions for the treatment of glaucoma and lay the foundation for new treatment strategies for glaucoma.

Efficacy and Safety of Tyrosine Kinase Inhibitors in Patients with Metastatic Pheochromocytomas/Paragangliomas.

CONTEXT: Tyrosine kinase inhibitors (TKIs) can be used to treat locally unresectable or distantly metastatic pheochromocytomas/paragangliomas (PPGLs), such as sunitinib, according to the National Comprehensive Cancer Network guidelines in 2022. However, the precise effect of different TKIs in metastatic PPGLs is still unclear. OBJECTIVE: The aim of this meta-analysis is to assess the efficacy and safety of TKIs in metastatic PPGLs. METHODS: The PubMed, Cochrane Library, Scopus, Clinical Trial, and Embase databases were searched by synonyms of 48 TKIs and metastatic PPGLs from inception up to August 2022. Outcomes were tumor response or survival data and the incidence of adverse events (AEs) after treatment. The MIONRS scale and the JBI's tools for case series were used for interventional and observational studies to assess risk of bias, respectively. The combined effects with fixed- or random-effect models, the combined median with the weighted median of medians method and their 95% CIs were reported. RESULTS: A total of 7 studies with 160 patients were included. Tumor responses in metastatic PPGLs in 5 studies with available data showed the pooled proportion of partial response (PR), stable disease, and disease control rate (DCR) of, respectively, 0.320 (95% CI 0.155-0.486), 0.520 (95% CI 0.409-0.630), and 0.856 (95% CI 0.734-0.979). The combined median progressive-free survival in 6 studies was 8.9 months (95% CI 4.1-13.5) and the proportion of those who discontinued due to AEs in 5 studies was 0.143 (95% CI 0.077-0.209). CONCLUSION: This meta-analysis suggests that patients with metastatic PPGLs can benefit from TKI therapy with PR and DCR up to more than 30% and 80%. However, because of restricted studies, larger clinical trials should be performed in the future.

Hyperparathyroidism in a Large Cohort of Chinese Patients With Tumor-induced Osteomalacia.

CONTEXT: Tumor-induced osteomalacia (TIO) is a rare paraneoplastic syndrome caused by excessive production of fibroblast growth factor 23 (FGF23) by a tumor. Hyperparathyroidism (HPT) including secondary HPT (SHPT) and tertiary HPT (THPT) in TIO patients, which is believed to be associated with phosphate supplementation, has not been well documented. OBJECTIVES: To clarify the prevalence, clinical characteristics, and risk factors for HPT in a large cohort of Chinese patients with TIO in our hospital. DESIGN, SETTING, AND PARTICIPANTS: This retrospective study enrolled 202 patients with TIO. MAIN OUTCOME MEASUREMENTS: Occurrence of HPT in patients with TIO. RESULTS: HPT was observed in 91 patients (91/202, 45.1%): 84 patients (41.6%) with SHPT and 7 patients (3.5%) with THPT. All patients with THPT underwent parathyroidectomy and only 1 patient experienced recurrence. Compared with patients without HPT, patients with SHPT had longer disease duration, higher rate of phosphate and calcitriol supplementation, lower serum calcium, lower urine calcium excretion, and higher urine phosphate excretion. Compared with patients with SHPT, patients with THPT had even longer disease duration and a higher rate of phosphate and calcitriol supplementation. PTH levels showed positive correlation with intact FGF23 and 1,25-dihydroxyvitamin D levels, but not 25-hydroxy vitamin D level in patients with TIO. Multivariate logistic regression analysis showed that long disease duration and phosphate supplementation were independently associated with occurrence of HPT in patients with TIO. Further logistic regression analysis and restricted cubic spline model revealed dose-response relationship between cumulative dose of phosphate supplementation and PTH levels. CONCLUSIONS: HPT is common in patients with TIO. To avoid the occurrence of HPT in patients with TIO, timely diagnosis and tumor resection is necessary and an excessive dose of phosphate supplementation is not suggested before surgery.

Oridonin Alters Hepatic Urea Cycle via Gut Microbiota and Protects against Acetaminophen-Induced Liver Injury.

Acetaminophen (APAP) hepatotoxicity is the leading cause of acute liver failure in the western world. Oridonin (OD), which is the major active ingredient of the traditional Chinese medicine Rabdosia rubescens, reportedly exerts anti-inflammatory and antioxidative effects. Here, we first find that OD protects against APAP-induced hepatotoxicity. The results of hepatic tissue-associated RNA-seq and metabolomics showed that the protective effects of OD were dependent upon urea cycle regulation. And such regulation of OD is gut microbiota partly dependent, as demonstrated by fecal microbiota transplantation (FMT). Furthermore, using 16S rRNA sequencing, we determined that OD significantly enriched intestinal Bacteroides vulgatus, which activated the nuclear factor erythroid 2-related factor 2 (Nrf2) pathway to regulate redox homeostasis against APAP by urea cycle. In conclusion, our study suggests that the Bacteroides vulgatus-urea cycle-Nrf2 axis may be a potential target for reducing APAP-induced liver injury, which is altered by OD.

Alleviating Na+ effect on phosphate and potassium recovery from synthetic urine by K-struvite crystallization using different magnesium sources.

Human urine is characterized by high concentrations of nitrogen (N), phosphorus (P) and potassium (K), of which the P and K can be recovered as K-struvite crystals. This study first investigated the formation of Na-struvite because of the high Na+ present in the urine. From the results, the optimal pH for the Na-struvite crystallization was observed to be 12, and the rise in the Na+ concentration distinctly favored the Na-struvite formation. As magnesium needed to be added to induce the K-struvite crystallization, several magnesium sources including MgCl2, Mg sacrificial electrode and Mg(OH)2 were applied to recover P and K from synthetic urine. The findings indicated that when MgCl2 was used as the magnesium source, the K removal could be slightly enhanced by prolonging the reaction time, which would correspondingly decrease the Na concentration in the precipitates; besides, the intermittent addition of MgCl2 could noticeably improve the removal efficiency of K by 6%, but simultaneously raise the Na content in the precipitates recovered. With respect to the use of the Mg sacrificial electrode, the recovery efficiencies of the P and K from synthetic urine were close to those with the use of MgCl2. However, when Mg(OH)2 was used as the magnesium source, the recovery efficiencies of P and K achieved only roughly 50%, which was much lower than those noted when MgCl2 and the Mg sacrificial electrode were employed. A comprehensive analysis revealed that the MgCl2 was the best magnesium source for the K-struvite crystallization, followed by the Mg sacrificial electrode and Mg(OH)2.

Central Blood Pressure Responses to Dietary Sodium and Potassium Interventions.

BACKGROUND: To explore how central hemodynamics respond to dietary sodium and potassium interventions, and whether the responses are associated with metabolic traits. METHODS: We conducted a dietary intervention study including a 7-day low-sodium (51.3 mmol sodium/day) intervention, a 7-day high-sodium (307.8 mmol sodium/day) intervention, and a 7-day high-sodium with potassium supplementation (60.0 mmol potassium/day) intervention among 99 northern Chinese subjects aged 18-60 years. Five metabolic traits included abdominal obesity, high triglycerides, low HDL cholesterol, raised blood pressure (BP), and high glucose. Central hemodynamics were measured at baseline and during each intervention. RESULTS: Central systolic BP (SBP), diastolic BP (DBP), pulse pressure (PP), and augmentation index (AIx@75) significantly decreased during low-sodium intervention, increased during high-sodium intervention, and then decreased during potassium supplementation. We observed potential linear trends toward significance of central SBP and PP responses to low-sodium intervention, and significant linear trends of responses to high-sodium intervention as the number of metabolic traits grows. For example, among participants with 0 or 1, 2 or 3, and 4 or 5 metabolic traits, central SBP responses to high-sodium intervention were 8.8 [95% confidence interval (5.8, 11.8)], 9.3 (7.1, 11.6), and 14.0 (11.6, 16.3) mmHg, respectively (P for trend = 0.009). Significant linear trends of central SBP and DBP responses to potassium supplementation were also observed. CONCLUSIONS: Central BP and AIx@75 were lowered by sodium reduction and potassium supplementation, and elevated by sodium-loading. The responses of central BP were pronounced among individuals with metabolic traits clustering. CLINICAL TRIALS REGISTRATION: Trial Number NCT00721721 (The current study is registered on ClinicalTrials.gov; https://clinicaltrials.gov).

[Application of shear wave elastography in the evaluation of neck-shoulder myofascial pain syndrome].

OBJECTIVE: To study clinical value of shear wave elastography (SWE) in the evaluation of neck-shoulder myofascial pain syndrome. METHODS: From December 2013 to July 2014,30 patients diagnosed as neck-shoulder myofascial pain syndrome were in the treatment group,including 17 males and 13 females, with an average age of (44 ± 3) years old. Thirty healthy people were in the control group, including 22 males and 8 females, with a mean age of (37 ± 5) years old. The patients in the treatment group were treated with manipulation, once every other day, total 7 times. The SWE was used to detect tension part of trapezius muscle of patients in the treatment group before and after treatment, as well as to detect muscle belly at the descending part of trapezius muscle in the control group. The tissue elasticity and Yang's modulus value were recorded and compared. RESULTS: The tissue elasticity chart of patients in the treatment group before treatment was mainly greenish blue with the score of 3.70 ± 1.53, and the Yang's modulus was (43.4 ± 15.6) kPa. The tissue elasticity figure after treatment was mainly blue with the score of 2.40 ± 0.87, and the Yang's modulus was (29.0 ± 5.9) kPa. Whereas in the control group, the tissue elasticity figure was mainly blue with the score of 1.60 ± 0.72, and the Yang's modulus was (24.0 ± 7.6) kPa. These were statistical differences between the two groups (P = 0.000). CONCLUSION: SWE can be used as an evaluation method of manipulation treatment for neck-shoulder myofascial pain syndrome, which is an objective and sensitive detection method.