A comprehensive review of protein misfolding disorders, underlying mechanism, clinical diagnosis, and therapeutic strategies.

INTRODUCTION: Proteins are the most common biological macromolecules in living system and are building blocks of life. They are extremely dynamic in structure and functions. Due to several modifications, proteins undergo misfolding, leading to aggregation and thereby developing neurodegenerative and systemic diseases. Understanding the pathology of these diseases and the techniques used to diagnose them is therefore crucial for their effective management . There are several techniques, currently being in use to diagnose them and those will be discussed in this review. AIM/OBJECTIVES: Current review aims to discuss an overview of protein aggregation and the underlying mechanisms linked to neurodegeneration and systemic diseases. Also, the review highlights protein misfolding disorders, their clinical diagnosis, and treatment strategies. METHODOLOGY: Literature related to neurodegenerative and systemic diseases was explored through PubMed, Google Scholar, Scopus, and Medline databases. The keywords used for literature survey and analysis are protein aggregation, neurodegenerative disorders, Alzheimer's disease, Parkinson's disease, systemic diseases, protein aggregation mechanisms, etc. DISCUSSION /CONCLUSION: This review summarises the pathogenesis of neurodegenerative and systemic disorders caused by protein misfolding and aggregation. The clinical diagnosis and therapeutic strategies adopted for the management of these diseases are also discussed to aid in a better understanding of protein misfolding disorders. Many significant concerns about the role, characteristics, and consequences of protein aggregates in neurodegenerative and systemic diseases are not clearly understood to date. Regardless of technological advancements, there are still great difficulties in the management and cure of these diseases. Therefore, for better understanding, diagnosis, and treatment of neurodegenerative and systemic diseases, more studies to identify novel drugs that may aid in their treatment and management are required.

Causes and treatment strategies of unilateral leaflet escape of bileaflet mechanical prosthetic heart valves after surgery: a case series.

BACKGROUND: During the eleven years from 2010 to 2021, preliminary statistics have shown that Fuwai Hospital completed 23,571 mechanical valve replacements for various types of valves, and 1139 mechanical valve replacements were performed in Guangyuan First People's Hospital. Only two patients developed valve leaflet escape, so valve leaflet escape is a rare postoperative complication. CASE PRESENTATION: In 2010 and 2021, two patients were selected after they had unilateral leaflet escape after having mechanical valve replacements in Fuwai Hospital of Chinese Academy of Medical Sciences and Guangyuan First People's Hospital. Both patients underwent reoperations with the classic operation and the new bileaflet mechanical prosthetic heart valve was sutured. The treatment of detached single lobe and distal vessel was comprehensively determined, and the condition was treated according to the patient's symptoms, CT results, ultrasound results and other test results, as well as whether this detached lobe caused any abnormal hemodynamics of the distal vessel. The patient with mechanical aortic valve escape completed the 10-year follow-up, and patient with mechanical mitral valve escape completed the 3-month follow-up. there was no thrombosis or hematoma at the embolic site; the patient had no lower limb symptoms. CONCLUSIONS: The reason for the leaflet escape may be related to the valve design and the leaflet material. If the detached leaflets are damaged and if the distal blood vessels are affected, simultaneous surgical treatment is required. Those patients whose vessels were not damaged by the valve lobe should be carefully monitored.

Etiology Analysis and Diagnosis and Treatment Strategy of Traumatic Brain Injury Complicated With Hyponatremia.

Objective: To explore the etiology and diagnosis and treatment strategy of traumatic brain injury complicated with hyponatremia. Methods: 90 patients with traumatic brain injury admitted to our hospital from December 2019 to December 2020 were retrospectively analyzed and divided into hyponatremic group (50 patients) and non-hyponatremic group (40 patients) according to the patients' concomitant hyponatremia, and the clinical data of the two groups were collected and compared. In addition, patients in the hyponatremia group were divided into a control group and an experimental group of 25 patients each according to their order of admission, with the control group receiving conventional treatment and the experimental group using continuous renal replacement therapy (CRRT). Hemodynamic indices, mortality and serum neuron-specific enolase (NSE) indices before and after treatment were compared between the control and experimental groups. The Glasgow coma scale (GCS) was used to assess the degree of coma before and after the treatment in the two groups, and the patients' disease status was assessed using the Acute Physiological and Chronic Health Evaluation Scoring System (APACHE II). Results: The etiology of traumatic brain injury complicated with hyponatremia is related to the degree of brain injury, ventricular hemorrhage, cerebral edema, and skull base fracture (P < 0.05). After the treatment, the hemodynamic indexes, APACHE II scores, death rate, and NSE levels of the experimental group were significantly lower than those of the control group (P < 0.001); The experimental group yielded remarkably higher GAC scores as compared to the control group (P < 0.001). Conclusion: The degree of brain injury, ventricular hemorrhage, cerebral edema, and skull base fracture were considered to be the main factors for traumatic brain injury complicated with hyponatremia. Continuous renal replacement therapy can effectively improve the clinical indicators of the patients with a promising curative effect, which merits promotion and application.

Perioperative diagnosis and treatment strategies of liver transplantation for liver cancer in precision medicine era / 中华消化外科杂志

Tumor recurrence and metastasis after liver transplantation (LT) remains one of the most important factors that affect the outcome of LT for hepatocellular carcinoma (HCC). The diagnosis and treatment strategies in the era of precision medicine, including utilizing multi-omics, high-throughput gene sequencing analysis, big data and artificial intelligence to select the biomarkers which can accurately predict the prognosis after LT, evaluating the immune status comprehensively, inducing immune tolerance, providing effective prevention for patients at a high risk of recurrence with sensitive antitumor drugs and attaching importance to individualized treatment for recurrence and metastasis, may further improve the outcome of LT. Combined with experience and review of relevant research articles, the authors elaborate perioperative diagnosis and treatment strategies of LT for HCC, aiming to promote the application of precision medicine in the field of LT.

[Diagnosis and treatment strategies of hepatitis C-related hepatocellular carcinoma in the era of direct-acting antiviral drugs].

The occult progression of chronic hepatitis C (CHC) is one of the main causes of liver cirrhosis and hepatocellular carcinoma (HCC). Recently, antiviral treatment of CHC has achieved great progress with the advent of direct-acting antiviral drugs (DAA), especially for special populations including advanced liver disease and HCC. However, DAA and HCC-related issues have also become one of the important concerns of current CHC treatment. This article summarizes the recent research progresses made in the diagnosis and treatment of HCV-related HCC.

[Surgical treatment for esophageal cancer during the outbreak of COVID-19].

Since December 2019, unexplained pneumonia has appeared in Wuhan City, Hubei Province, and a new type of coronavirus infection was confirmed as COVID-19. COVID-19 spread rapidly nationwide and abroad. The COVID-19 has brought huge impacts to all the people and walks of life, especially to the medical and health systems. It has also brought great challenges to the treatment of patients with cancer. Esophageal cancer is a common malignant tumor in China and most of the patients are in the middle and advanced stage when diagnosed, with immunosuppressive and poor prognosis. The selection of surgical procedures and perioperative managements of esophageal cancer require all thoracic surgeons work together to figure out a reasonable system of surgical treatment and emergency response.

Surgical treatment for esophageal cancer during the outbreak of COVID-19 / 中华肿瘤杂志

Since December 2019, unexplained pneumonia has appeared in Wuhan City, Hubei Province, and a new type of coronavirus infection was confirmed as COVID-19. COVID-19 spread rapidly nationwide and abroad. The COVID-19 has brought huge impacts to all the people and walks of life, especially to the medical and health systems. It has also brought great challenges to the treatment of patients with cancer. Esophageal cancer is a common malignant tumor in China and most of the patients are in the middle and advanced stage when diagnosed, with immunosuppressive and poor prognosis. The selection of surgical procedures and perioperative managements of esophageal cancer require all thoracic surgeons work together to figure out a reasonable system of surgical treatment and emergency response.

Diagnosis and treatment strategy for advanced severe lung cancer / 中国实用内科杂志

Advanced severe lung cancer means the stage IIIB, IIIC, and IV lung cancer patients with a PS score of 2 to 4 points due to various related causes of lung cancer itself or the complication of anti-tumor drugs, with a high probability of benefiting from the existing systemic anti-tumor treatments. The diagnosis and treatment strategies emphasize the implementation of minimally invasive dynamic monitoring mutation targets and curative effects. Every drug that is useful to the patient should be used as possible, and making the best use of every drug as possible with the help of respiratory support therapy. Specific treatment concepts include combination therapy,alternating medication, paying equal attention to systemic therapy and local therapy, PS score assessment, upgrading and downgrading of drug use, and simultaneous treatment of cancer and lung itself.

Endoscopic Ultrasonography in the Diagnosis and Treatment Strategy Choice of Esophageal Leiomyoma

OBJECTIVES: Esophageal leiomyoma is the most common benign tumor of the esophagus, and it originates from mesenchymal tissue. This study analyzed the clinicopathological characteristics of esophageal leiomyoma and aimed to evaluate the role of endoscopic ultrasonography in the diagnosis and treatment selection for these lesions. METHODS: Two hundred and twenty-five patients who had suspected esophageal leiomyomas in endoscopic ultrasonography were enrolled at the Endoscopy Center of The First Affiliated Hospital, Zhejiang University from January 1st, 2009 to May 31th, 2015. The main outcomes included the demographic and morphological characteristics, symptoms, comparisons of diagnosis and treatment methods, adverse events, and prognosis. RESULTS: One hundred and sixty-seven patients were diagnosed as having an esophageal leiomyoma by pathological examination. The mean patient age was 50.57±9.983 years. In total, 62.9% of the lesions originated from the muscularis mucosa, and the others originated from the muscularis propria. The median distance to the incisors was 30±12 cm. The median diameter was 0.72±0.99 cm. As determined by endoscopic ultrasonography, most existing leiomyomas were homogeneous, endophytic, and spherical. The leiomyomas from the muscularis mucosa were smaller than those from the muscularis propria and much closer to the incisors (p<0.05). SMA (smooth muscle antibody) (97.2%) and desmin (94.5%) were positive in the majority of patients. In terms of treatments, patients preferred endoscopic therapies, which led to less adverse events (e.g., intraoperative bleeding, local infection, pleural effusion) than surgical operations (p<0.05). The superficial leiomyomas presented less adverse events and better recovery (p<0.05) than deep leiomyomas. CONCLUSION: Endoscopic ultrasonography has demonstrated high accuracy in the diagnosis of esophageal leiomyomas and provides great support in selecting treatments; however, EUS cannot completely avoid misdiagnosis, so combining it with other examinations may be a good strategy to solve this problem.

Recent advances in the diagnosis and treatment of refractory epilepsy / 中国综合临床

The refractory epilepsy refers to the epilepsy whose seizures couldn't be cured after using two kinds of correctly selected antiepileptic drugs which can be tolerated and enough dosage and duration of monotherapy or combination therapy.The pathogenesis of intractable epilepsy is complex,and there is no established theory at home and abroad.Recently,more and more attention has been paid to the correlation between mitochondrial dysfunction caused by oxidative stress and intractable epilepsy.Based on the summary of common treatment of refractory epilepsy and by searching the related literature at home and abroad,further investigation would be made to explore the diagnosis and treatment of intractable epilepsy theory in order to provide new strategies for diagnosis and treatment of intractable epilepsy.

Advances in diagnosis and treatment of thymic carcinoid / 基础医学与临床

Thymic carcinoid is a rare neoplasm with unclear risk factors and controversial classifications .Clinical manifestations vary from asymptomatic to many nonspecific symptoms , among which endocrinopathy seems to be as-sociated with poor prognosis .Image studies show no specificity both in CT and PET/CT, but are of great value in clinical staging .Ki67 index has been found to be a powerful tool for grading neuroendocrine tumors and further studies should be made .The diagnosis of thymic carcinoid mainly depends on pathology and immunohistochemistry plays a role in differential diagnosis .Radical resection is the first choice in treatment , and target therapy becomes possible with the development in molecular pathology .