Tafamidis is a selective stabilizer for transthyretin （TTR）， used for the treatment of transthyretin amyloidosis with cardiomyopathy （ATTR-CM） and transthyretin amyloidosis with polyneuropathy （ATTR-PN）. This article provides a review of the basic information and clinical studies on the efficacy and safety of tafamidis. It is found that tafamidis slows down or prevents the progression of TTR amyloidosis by inhibiting the dissociation of TTR tetramers. Multiple clinical studies have shown that tafamidis has good efficacy and safety， significantly reducing all-cause mortality and cardiovascular-related hospitalization rates in patients with amyloidosis， and delaying disease progression. Although tafamidis treatment may have certain limitations， it is still a key drug for the treatment of TTR amyloidosis， and the first drug approved for the treatment of ATTR-CM.

Lecanemab is a new drug used to treat early Alzheimer's disease (AD) with mild cognitive impairment or mild dementia. It is a human anti-Aβ fibril monoclonal IgG1 antibody, which is injected intravenously into the patient, through the blood-brain barrier into the brain, clearing amyloid plaque, thereby slowing the rate of cognitive decline in patients and delaying disease progression. This article reviews the pharmacological studies, clinical studies, safety and limitations of lecanemab, in order to help clinical understand the current research status and existing achievements of this drug.

OBJECTIVE To optimize the rivaroxaban dosing regimen for anticoagulation in patients with different renal function levels. METHODS The administration regimen was determined based on the drug instructions for rivaroxaban and the actual medication situation of the patient. The target concentration range and the subsection interval were established using rivaroxaban blood minimum concentration for patients from Hebei General Hospital and reference range of rivaroxaban laboratory monitoring concentration recommended by International Council for Standardization in Hematology. The probability of different dosing regimens in each target concentration range was investigated with Monte Carlo simulation using Oracle Crystal Ball software （V11.1.2.4）. RESULTS A total of 97 patients with non-valvular atrial fibrillation were enrolled and the minimum concentration of rivaroxaban was tested 125 times with a median trough concentration of 32.2 ng/mL； a total of 121 patients with venous thrombosis were enrolled and the minimum concentration was tested 159 times with a median minimum concentration of 31.0 ng/mL. The reference range for steady-state minimum concentration in patients with non-valvular atrial fibrillation was 12-137 and 3-153 ng/mL， while the reference range for steady-state minimum concentration in patients with venous thrombosis was 6-239 and 3-224 ng/mL. Monte Carlo simulation results showed that in patients with non-valvular atrial fibrillation， the optimal rivaroxaban dosing regimen for patients with glomerular filtration rate （eGFR） 0-30 mL/min was 5 mg once daily； for patients with eGFR＞30-60 mL/min， the optimal dosing regimen was 10-20 mg once daily or 5 mg twice daily； for patients with eGFR＞60-90 mL/min， the optimal dosing regimen was 15-30 mg once daily or 5-10 mg twice daily； for patients with eGFR＞90-120 mL/min， the optimal dosing regimen was 25-30 mg once daily or 5-15 mg twice daily. For patients with venous thrombosis， it is not recommended to use rivaroxaban more than 5 mg once daily for patients with eGFR 0-30 mL/min； the optimal dosing regimens of rivaroxaban were 5 mg once daily for patients with eGFR＞30-60 mL/min， 25- 30 mg once daily or 5-15 mg twice daily for patients with eGFR＞60-90 mL/min， 10-15 mg twice daily for patients with eGFR＞ 90-120 mL/min. CONCLUSIONS Rivaroxaban should be selected carefully as the anticoagulants for patients with severe renal function impairment. Rivaroxaban possesses a wide reference range in the minimum concentration and considerable individual variability. The dosage and frequency of rivaroxaban can be personalized through the Monte Carlo simulation method， taking into account patients’ renal function.

Immunoglobulin A nephropathy is a common autoimmune nephropathy.A growing body of research suggests that immunoglobulin A nephropathy may be associated with dysfunction of the mucosal immune system.Immunoglobulin A nephropathy is characterized by thylakoid deposi-tion of galactose-deficient IgA1 immune complex-es,which are thought to originate from mucosal B-cells,which are abundantly present in the distal ile-um,which is rich in Pyle's collecting lymph nodes.A novel targeted release formulation of budesonide has been shown to deliver the drug to the distal ileum with the aim of minimizing adverse events in patients with immunoglobulin A nephrop-athy.This article reviews the mechanism of action,dosage form characteristics,clinical studies,drug interactions and adverse events,and limitations of budesonide extended-release capsules.

Objective:To quantify any correlation between the severity of spinal curvature of an adolescent with idiopathic scoliosis and their cardiopulmonary exercise endurance.Methods:The cardiopulmonary exercise test (CPET) results and the full-length spinal X-rays in a standing position of 64 adolescents with idiopathic scoliosis were reviewed retrospectively. Independent t-tests were used to compare the two datasets obtained from those with left or right thoracic scoliosis. The correlation between the Cobb angle and cardiopulmonary exercise endurance was analyzed using Pearson correlation coefficients, multiple factor linear regression and two-stage linear regression.Results:After adjusting for gender, age, height and weight, the multiple linear regression analysis showed that the Cobb angle was significantly negatively correlated with maximum tidal volume (β=-0.013) and significantly positively correlated with the rate of respiration (β=0.421). The relationship between the Cobb angle and cardiopulmonary exercise endurance was non-linear. With a Cobb angle > 34°, a 1° increase reduces cardiopulmonary exercise endurance by a factor of 1.4 on average. At smaller Cobb angles the corresponding increase is about 0.87 times.Conclusions:The Cobb angle is a negative predictor of ventilation during exercise among adolescents with idiopathic scoliosis. The more severe a patient′s spinal curvature, the lower the cardiopulmonary exercise endurance is likely to be.

Background::The pharmacokinetic and clinical behaviors of many proton pump inhibitors (PPIs) in peptic ulcer treatment are altered by CYP2C19 genetic polymorphisms. This non-inferiority study evaluated the efficacy and safety of the novel PPI anaprazole compared with rabeprazole. We also explored the influence of Helicobacter pylori ( H. pylori) infection status and CYP2C19 polymorphism on anaprazole. Methods::In this multicenter, randomized, double-blind, double-dummy, positive-drug parallel-controlled, phase III study, Chinese patients with duodenal ulcers were randomized 1:1 to receive rabeprazole 10 mg + anaprazole placebo or rabeprazole placebo + anaprazole 20 mg once daily for 4 weeks. The primary efficacy endpoint was the 4-week ulcer healing rate assessed by blinded independent review. Secondary endpoints were the proportion of patients with improved overall and individual duodenal ulcer symptoms at 4 weeks. Furthermore, exploratory subgroup analysis of the primary endpoint by H. pylori status and CYP2C19 polymorphism was conducted. Adverse events were monitored for safety. Non-inferiority analysis was conducted for the primary endpoint. Results::The study enrolled 448 patients (anaprazole, n = 225; rabeprazole, n = 223). The 4-week healing rates were 90.9% and 93.7% for anaprazole and rabeprazole, respectively (difference, -2.8% [95% confidence interval, -7.7%, 2.2%]), demonstrating non-inferiority of anaprazole to rabeprazole. Overall duodenal ulcer symptoms improved in 90.9% and 92.5% of patients, respectively. Improvement rates of individual symptoms were similar between the groups. Healing rates did not significantly differ by H. pylori status or CYP2C19 genotype for either treatment group. The incidence of treatment-emergent adverse events was similar for anaprazole (72/220, 32.7%) and rabeprazole (84/219, 38.4%). Conclusions::The efficacy of anaprazole is non-inferior to that of rabeprazole in Chinese patients with duodenal ulcers.Registration::ClinicalTrials.gov, NCT04215653.

Objective:To investigate the clinicopathological features, diagnosis and differential diagnosis of notochordal tumors.Methods:The clinical, radiologic and pathologic data of 48 notochordal tumors were collected from 2008 to 2019 at Shanghai Jiaotong University Sixth People′s Hospital. Expression of cytokertin, S-100 protein, vimentin, brachyury and INI1 was detected by immunohistochemistry. The pathologic differential diagnoses and biologic behavior of various types of notochordal tumors were analyzed using the new standard in the 5th edition of WHO tumor classification.Results:Four cases of benign notochordal cell tumor were confined to vertebral body. Histopathologically, they lacked lobular architecture and extracellular myxoid matrix. The tumor cells were vacuolated and had centrally or peripherally located round to oval nuclei, with small nucleoli, without atypia, mimicking mature adipocytes. No mitotic figures were seen. Two cases of poorly differentiated chordoma, from patients aged 12 years and 21 years respectively, were located in cervical vertebra, and were composed of cohesive sheets or nests of epithelioid cells, with focal rhabdoid morphology. There was relatively abundant eosinophilic cytoplasm and scattered cytoplasmic vacuoles. The moderately pleomorphic nuclei were round to ovoid with vesicular chromatin and mitotic figures could be seen. Extracellular myxoid stroma was observed focally. Forty cases of conventional chordoma and two cases of extra-axis chordoma had similar histologic features. All 48 cases expressed cytokeretin, 45 cases expressed brachyury, and two poorly differentiated tumors showed loss of INI1/SMARCB1.Conclusions:There are four subtypes of chordomas: conventional, dedifferentiated, poorly differentiated and extra-axis. Chondroid chordoma is no longer thought to be a distinct entity. Each type has its unique clinicopathological characteristics. Brachyury is highly specific and sensitive for the diagnosis of various notochordal tumors. Poorly differentiated chordoma shows distinct clinicopathological features, including young age and loss of immunohistochemical expression of INI1/SMARCB1, and its diagnosis requires the combined detection of brachyury and INI1/SMARCB1.

Autophagy is a process of degrading the damaged organelles and macromolecules by lysosomes in cells, which belongs to the programmed cell death. Cerebral ischemia is one of the important reasons for activation of autophagy. Studies have showed that autophagy plays a protective role in neuronal death induced by ischemia. However, it has also been found that excessive activation of autophagy could aggravate cerebral ischemia injury. In recent years, more and more Chinese medicine has been proved to regulate the autophagy level of brain neurons and reduce cerebral ischemia injury. In this paper, the main molecular mechanism of autophagy in the process of cerebral ischemic injury and the intervention effects of Chinese herbs on autophagy arereviewed in order to explore the basic principle of regulating autophagy by Chinese herbs and to play a better role in the clinical treatment of cerebral ischemic diseases.
Autophagy ; Brain Ischemia ; Cell Death ; Cerebral Infarction ; Humans ; Medicine, Chinese Traditional

Autophagy is a process of degrading the damaged organelles and macromolecules by lysosomes in cells, which belongs to the programmed cell death. Cerebral ischemia is one of the important reasons for activation of autophagy. Studies have showed that autophagy plays a protective role in neuronal death induced by ischemia. However, it has also been found that excessive activation of autophagy could aggravate cerebral ischemia injury. In recent years, more and more Chinese medicine has been proved to regulate the autophagy level of brain neurons and reduce cerebral ischemia injury. In this paper, the main molecular mechanism of autophagy in the process of cerebral ischemic injury and the intervention effects of Chinese herbs on autophagy arereviewed in order to explore the basic principle of regulating autophagy by Chinese herbs and to play a better role in the clinical treatment of cerebral ischemic diseases.

OBJECTIVE： To investigate the changes of extraction rates of forsythiaside A and forsythin in Forsythia suspensa compatible with other medicinal material of Menshi huwei formula before and after decoction. METHODS： HPLC method was used to determine the extraction amounts and to calculate the extraction rates of forsythiaside A and forsythin in F. suspensa （5 g×7 doses）， F. suspensa （5 g×7 doses） compatible with Pinelliae rhizoma praeparatum cum zingibere et alumine （PRZA）， Menshi huwei formula [including 6 ingredients as F. suspense （5 g×7 doses）， PRZA] after decocted with water. The determination was performed on Diamonsil C18 column with mobile phase consisted of acetonitrile-0.2％ formic acid solution （gradient elution）. The detection wavelength was set at 278 nm， and the column temperature was 30 ℃. The flow rate was 1.0 mL/min. RESULTS： The linear range of forsythiaside A and forsythin were 0.61-6.1， 0.246-2.46 μg （r＝0.999 7， 0.999 9）， respectively； RSDs of precision， stability （within 20 h） and reproducibility tests were all lower than 2％ （n＝6）. Average recovery rates were 96.10％-99.37％ （RSD≤2.36％，n＝6） respectively. In F. suspensa， extraction rates of forsythiaside A and forsythin were 96.90％ and 66.67％. In F. suspensa compatible with PRZA， extraction rates of them were 101.61％ and 54.55％. In Menshi huwei formula， extraction rates of them were 98.39％ and 84.85％. CONCLUSIONS： After F. suspensa is compatible with PRZA， the extraction rates of forsythiaside A is increased while forsythin is decreased. After compatible with other medicinal material in Menshi huwei formula， extraction rates of both are increased slightly.