Endoscopic endonasal transsphenoidal approach improves endocrine function and surgical outcome in primary craniopharyngioma resection: a systematic review and meta-analysis.

BACKGROUND: Craniopharyngiomas (CPs) are generally derived from the craniopharyngeal duct epithelium, accounting for 38% and 24.5% of mortality in pediatric and adult patients, respectively. At present, the widespread application of the endoscopic endonasal transsphenoidal approach (EEA) has led to controversy between the traditional microscopic transcranial approach (TCA) and EEA in relation to the surgical management of CPs. OBJECT AND METHOD: We performed a systematic review and meta-analysis comparing the complications, surgical outcomes, and endocrine functions of patients with CPs to provide evidence-based decision-making in their surgical management. RESULT: Overall, 11 observational studies with 12,212 participants were included in the meta-analysis, in which five of them only included an adult population, three of them only included a child population, and the other three studies included a mixed population (adult and child). In pediatric patients, the EEA achieved a higher gross total resection (GTR) rate (odds ratio (OR) = 5.25, 95%CI: 1.21-22.74), lower recurrence rate (OR = 0.54, 95%CI: 0.31-0.94, p = 0.030), and less hypopituitarism (OR = 0.34, 95%CI: 0.12-0.97, p = 0.043). In adult patients, EEA significantly improved mortality (OR = 0.09, 95%CI: 0.06-0.15, p < 0.001) and visual outcomes (visual improvement: OR = 3.42, 95%CI: 1.24-9.40, p = 0.017; visual deficit: OR = 0.30, 95%CI: 0.26-0.35) with decreases in postoperative stroke (OR = 0.58, 95%CI: 0.51-0.66, p < 0.001), hydrocephalus, and infections (OR = 0.32, 95%CI: 0.24-0.42, p < 0.001). CONCLUSION: Compared with the traditional TCA in primary CP resection, the development and wide application of EEA optimistically decreased the recurrence rate of CP, alleviated hypopituitarism with improvement in the GTR rate of pediatric patients, and significantly improved the visual outcomes, hydrocephalus, postoperative stroke, survival, and infection rates of the patients. Therefore, EEA is an optimal approach for primary CP resection.

Ductal Hyperkeratinization and Acinar Renewal Abnormality: New Concepts on Pathogenesis of Meibomian Gland Dysfunction.

Meibomian gland dysfunction (MGD) is a functional and morphological disorder of the meibomian glands which results in qualitative or quantitative alteration in meibum secretion and is the major cause of evaporative dry eye (EDE). EDE is often characterized by tear film instability, increased evaporation, hyperosmolarity, inflammation, and ocular surface disorder. The precise pathogenesis of MGD remains elusive. It has been widely considered that MGD develops as a result of ductal epithelial hyperkeratinization, which obstructs the meibomian orifice, halts meibum secretion, and causes secondary acinar atrophy and gland dropout. Abnormal self-renewal and differentiation of the acinar cells also play a significant role in MGD. This review summarizes the latest research findings regarding the possible pathogenesis of MGD and provides further treatment strategies for MGD-EDE patients.

Botulinum Neurotoxin Type a Injection Combined with Absorbable Punctal Plug Insertion: An Effective Therapy for Blepharospasm Patients with Dry Eye.

Blepharospasm patients often have dry eye manifestations. Botulinum neurotoxin type A (BoNT-A) injection has been the main management for blepharospasm and absorbable punctal plug (APP) insertion is shown to be effective in the treatment of dry eye. However, there have been no studies investigating the combined treatment of BoNT-A and APP in blepharospasm patients with dry eye. In this retrospective study, 17 blepharospasm patients with dry eye treated by BoNT-A injection and 12 receiving BoNT-A plus APP treatment were enrolled. The efficacy was evaluated according to the Jankovic rating scale, Ocular Surface Disease Index (OSDI), fluorescein staining (FL), fluorescein tear break-up time (FBUT) and Schirmer I test (SIT). Both BoNT-A and BoNT-A+APP treatment effectively reduced the functional impairment of blepharospasm. At baseline, all the patients had high OSDI scores (BoNT-A group: 82.48 ± 7.37, BoNT-A+APP group: 78.82 ± 4.60, p = 0.112), but relatively low degrees of FL (BoNT-A group: 3.18 ± 1.01, BoNT-A+APP group: 3.50 ± 1.24, p = 0.466), FBUT (BoNT-A group: 1.71 ± 0.77, BoNT-A+APP group: 2.17 ± 0.58, p = 0.077) and SIT (BoNT-A group: 2.53 ± 0.99, BoNT-A+APP group: 3.17 ± 1.23, p = 0.153). After treatment, OSDI, FL, FBUT and SIT were all obviously restored in the two groups. When comparing the changing rates, only OSDI (BoNT-A group: -52.23% ± 15.57%, BoNT-A+APP group: -61.84% ± 9.10%, p = 0.047) and FL (BoNT-A group: -22.55% ± 25.98%, BoNT-A+APP group: -41.94% ± 14.46%, p = 0.016) showed significant differences between the two groups. This study suggests that OSDI is not applicable in the diagnosis of dry eye among blepharospasm patients. For blepharospasm patients with severe dry eye symptoms, especially those with fluorescein staining in the cornea, the combined treatment of BoNT-A and APP is more effective than using BoNT-A alone.

Clinical Outcomes of Transcranial and Endoscopic Endonasal Surgery for Craniopharyngiomas: A Single-Institution Experience.

OBJECTIVE: Craniopharyngioma has always been a challenge for the neurosurgeon, and there is no consensus on optimal treatment. The objective of this study was to compare surgical outcomes and complications between transcranial surgery (TCS) and endoscopic endonasal surgery (EES) of craniopharyngiomas. METHODS: A retrospective review of patients who underwent craniopharyngioma resection at Wuhan Union Hospital between January 2010 and December 2019 was performed. A total of 273 patients were enrolled in this retrospective study. All patients were analyzed with surgical effects, endocrinologic outcomes, complications, and follow-up results. RESULTS: A total of 185 patients underwent TCS and 88 underwent EES. There were no significant differences in patient demographic data, preoperative symptoms, and tumor characteristics between the two groups. The mean follow-up was 30.5 months (range 8-51 months). The EES group had a greater gross total resection (GTR) rate (89.8% EES vs. 77.3% TCS, p < 0.05) and lower rate of hypopituitarism (53.4% EES vs. 68.1% TCS, p < 0.05) and diabetes insipidus (DI) (51.1% EES vs. 72.4% TCS, p < 0.05). More postoperative cerebrospinal fluid (CSF) leaks occurred in the EES group (4.5% EES vs. 0% TCS, p < 0.05). More patients in the EES group with preoperative visual deficits experienced improvement after surgery (74.5% EES vs. 56.3% TCS, p < 0.05). There were statistical differences in the recurrence rates (12.5% EES vs. 23.8% TCS, p < 0.05) between the 2 groups. CONCLUSION: These data support the view that EES is a safe and effective minimally invasive surgery compared to TCS. Compared to TCS, EES has fewer surgical complications and a lower recurrence rate.

1-Deoxynojirimycin and its Derivatives: A Mini Review of the Literature.

1-Deoxynojirimycin (1-DNJ) is a naturally occurring sugar analogue with unique bioactivities. It is found in mulberry leaves and silkworms, as well as in the metabolites of certain microorganisms, including Streptomyces and Bacillus. 1-DNJ is a potent α-glucosidase inhibitor and it possesses anti-hyperglycemic, anti-obese, anti-viral and anti-tumor properties. Some derivatives of 1-DNJ, like miglitol, miglustat and migalastat, were applied clinically to treat diseases such as diabetes and lysosomal storage disorders. The present review focused on the extraction, determination, pharmacokinetics and bioactivity of 1-DNJ, as well as the clinical application of 1-DNJ derivatives.

Clinical manifestations and evidence of neurological involvement in 2019 novel coronavirus SARS-CoV-2: a systematic review and meta-analysis.

BACKGROUND: Coronavirus disease 2019 (COVID-19) has become a global pandemic, affecting millions of people. However, clinical research on its neurological manifestations is thus far limited. In this study, we aimed to systematically collect and investigate the clinical manifestations and evidence of neurological involvement in COVID-19. METHODS: Three medical (Medline, Embase, and Scopus) and two preprints (BioRxiv and MedRxiv) databases were systematically searched for all published articles on neurological involvement in COVID-19 since the outbreak. All included studies were systematically reviewed, and selected clinical data were collected for meta-analysis via random-effects. RESULTS: A total of 41 articles were eligible and included in this review, showing a wide spectrum of neurological manifestations in COVID-19. The meta-analysis for unspecific neurological symptoms revealed that the most common manifestations were fatigue (33.2% [23.1-43.3]), anorexia (30.0% [23.2-36.9]), dyspnea/shortness of breath (26.9% [19.2-34.6]), and malaise (26.7% [13.3-40.1]). The common specific neurological symptoms included olfactory (35.7-85.6%) and gustatory (33.3-88.8%) disorders, especially in mild cases. Guillain-Barré syndrome and acute inflammation of the brain, spinal cord, and meninges were repeatedly reported after COVID-19. Laboratory, electrophysiological, radiological, and pathological evidence supported neurologic involvement of COVID-19. CONCLUSIONS: Neurological manifestations are various and prevalent in COVID-19. Emerging clinical evidence suggests neurological involvement is an important aspect of the disease. The underlying mechanisms can include both direct invasion and maladaptive inflammatory responses. More studies should be conducted to explore the role of neurological manifestations in COVID-19 progression and to verify their underlying mechanisms.

Neuroinflammation in Alzheimer's Disease: Microglia, Molecular Participants and Therapeutic Choices.

Alzheimer's disease is the world's most common dementing illness. It is pathologically characterized by ß-amyloid accumulation, extracellular senile plaques and intracellular neurofibrillary tangles formation, and neuronal necrosis and apoptosis. Neuroinflammation has been widely recognized as a crucial process that participates in AD pathogenesis. In this review, we briefly summarized the involvement of microglia in the neuroinflammatory process of Alzheimer's disease. Its roles in the AD onset and progression are also discussed. Numerous molecules, including interleukins, tumor necrosis factor alpha, chemokines, inflammasomes, participate in the complex process of AD-related neuroinflammation and they are selectively discussed in this review. In the end of this paper from an inflammation- related perspective, we discussed some potential therapeutic choices.

Portrait of glial scar in neurological diseases.

Fibrosis is formed after injury in most of the organs as a common and complex response that profoundly affects regeneration of damaged tissue. In central nervous system (CNS), glial scar grows as a major physical and chemical barrier against regeneration of neurons as it forms dense isolation and creates an inhibitory environment, resulting in limitation of optimal neural function and permanent deficits of human body. In neurological damages, glial scar is mainly attributed to the activation of resident astrocytes which surrounds the lesion core and walls off intact neurons. Glial cells induce the infiltration of immune cells, resulting in transient increase in extracellular matrix deposition and inflammatory factors which inhibit axonal regeneration, impede functional recovery, and may contribute to the occurrence of neurological complications. However, recent studies have underscored the importance of glial scar in neural protection and functional improvement depending on the specific insults which involves various pivotal molecules and signaling. Thus, to uncover the veil of scar formation in CNS may provide rewarding therapeutic targets to CNS diseases such as chronic neuroinflammation, brain stroke, spinal cord injury (SCI), traumatic brain injury (TBI), brain tumor, and epileptogenesis. In this article, we try to describe the new portrait of glial scar and trending of research in neurological diseases to readers.

Surgical treatment of poor grade middle cerebral artery aneurysms associated with large sylvian hematomas following prophylactic hinged craniectomy.

The clinical characteristics of patients who presented in poor clinical grade due to ruptured middle cerebral artery aneurysms (MCAAs) associated with large sylvian hematomas (SylH) were analyzed and an ingenious designed prophylactic hinged craniectomy was introduced. Twenty-eight patients were graded into Hunt-Hess grades IV-V and emergency standard micro-neurosurgeries (aneurysm clipping, hematoma evacuation and prophylactic hinged craniectomy) were performed, and their clinical data were retrospectively analyzed. 46.43% of the patients reached encouraged favorable outcomes on discharge. The favorable outcome group and the poor outcome group significantly differed in terms of patients' anisocoria, Hunt-Hess grade before surgery, extent of the midline shift and time to the surgery after bleeding (P<0.05). There were no significant differences in age, sex, volume and location of the hematoma, size of aneurysm between the favorable and poor groups (P>0.05). However, ingenious designed prophylactic hinged craniectomy efficiently reduced the patients' intracranial pressure (ICP) after surgery. It was suggested that preoperative conditions such as Hunt-Hess grading, extent of the midline shift and the occurrence of cerebral hernia affect the prognosis of patients, but time to the surgery after bleeding and prophylactic hinged craniectomy are of significant importance for optimizing the prognosis of MCAA patients presenting with large SylH.

Pharmacokinetics and retinal toxicity of various doses of intravitreal triamcinolone acetonide in rabbits.

PURPOSE: To compare the pharmacokinetics and retinal toxicity of various doses of intravitreal triamcinolone acetonide (TA) in rabbits. METHODS: The rabbits received intravitreal injections of 4 mg and 8 mg TA. The drug concentrations were determined with high-performance liquid chromatography after extraction from the vitreous at various time points. The main pharmacokinetics parameters were calculated with 3p97 pharmacokinetics software. The intraocular pressure, electroretinography, and pathological examinations were evaluated before and after intravitreal injection of different doses of TA. RESULTS: The half-life of intravitreal injection of 4 mg and 8 mg TA was 24 days and 34 days, respectively. No significant differences were found in intraocular pressure (p>0.05) and the electroretinography b-wave amplitudes (p>0.05) among the rabbits before and after intravitreal injection of 4 mg and 8 mg TA. Light and electron microscopy did not show any retinal damage in any group. CONCLUSIONS: Intravitreal injection of 4 mg and 8 mg TA are safe for the rabbit retina. The injection of 8 mg TA produced a longer vitreous half-life and had a prolonged effect on the retina. This conclusion may be referenced in the clinical application of TA in retinal diseases.

Focal cerebral ischemia induces Alzheimer's disease-like pathological change in rats.

The changes in the tau protein phosphorylation and expression of bcl-2, and bax in rat parietal cortex neurons after focal cerebral ischemia-reperfusion (I/R) were explored, and the relationship between the tau protein phosphorylation and the expression of bax or apoptosis was clarified in order to elucidate the relationship between cerebral infarction and Alzheimer's disease. The rat focal cerebral I/R model was induced by occlusion of the right middle cerebral artery using the intraluminal suture method. The level of tau protein phosphorylation at Ser396, Ser404, Tyr231, Ser199/202 sites and the expression of bcl-2, bax and total tau 5 in rat parietal cortex during focal cerebral ischemia/reperfusion were detected by Western blot. The relationship between the tau protein phosphorylation and the expression of bax, or apoptosis was examined by TUNEL method and double-labeling immunofluorenscence method. The results showed that the level of tau hyperphosphorylation at Ser199 / 202, Ser396, Ser404, Tyr231 sites and the expression levels of bcl-2, and bax were significantly higher in I/R group than in the sham group, but the ratio of bcl-2/bax was decreased. Neuronal apoptosis, bax expression and the tau protein hyperphosphorylation were co-localized. It is suggested that Alzheimer's disease-like pathological changes occur after cerebral I/R. The highly abnormal phosphorylation of tau protein plays a key role in cerebral I/R-induced apoptosis. The cerebral infarction may contribute to Alzheimer's disease occurrence and development.

Focal Cerebral Ischemia Induces Alzheimer's Disease-like Pathological Change in Rats / 华中科技大学学报（医学）（英德文版）

The changes in the tau protein phosphorylation and expression of bcl-2,and bax in rat parietal cortex neurons after focal cerebral ischemia-reperfusion(I/R)were explored,and the relationship between the tau protein phosphorylation and the expression of bax or apoptosis was clarified in order to elucidate the relationship between cerebral infarction and Alzheimer's disease.The rat focal cerebral I/R model was induced by occlusion of the right middle cerebral artery using the intraluminal suture method.The level of tau protein phosphorylation at Ser396,Ser404,Tyr231,Ser199/202 sites and the expression of bcl-2,bax and total tau 5 in rat parietal cortex during focal cerebral ischemia/reperfusion were detected by Western blot.The relationship between the tau protein phosphorylation and the expression of bax,or apoptosis was examined by TUNEL method and double-labeling immunofluorenscence method.The results showed that the level of tau hyperphosphorylation at Ser199/202,Ser396,Ser404,Tyr231 sites and the expression levels of bcl-2,and bax were significantly higher in I/R group than in the sham group,bat the ratio of bcl-2/bax was decreased.Neuronal apoptosis,bax expression and the tau protein hyperphosphorylation were co-localized.It is suggested that Alzheimer's disease-like pathological changes occur after cerebral I/R.The highly abnormal phosphorylation of tau protein plays a key role in cerebral I/R-induced apoptosis.The cerebral infarction may contribute to Alzheimer's disease occurrence and development.