Alzheimer disease is a progressive neurodegenerative disorder which has emerged as a major public health concern with the global population aging, and the development of effective therapeutic agents has become increasingly urgent due to its rapid increase in prevalence. There is some progress in drug development, however, the majority of new drugs have failed to demonstrate sustained clinical efficacy in large-scale trials. In addition, high costs, severe side effects have further hindered the widespread application of these therapies. This article reviews recent progress in the development of pharmacological treatments for Alzheimer disease, focusing on disease-modifying therapies targeting amyloid-β and tau proteins, also analyzes the results of phase 2 and phase 3 clinical trials of traditional and novel drugs. Future research efforts should continue to explore novel therapeutic targets and strategies to offer more effective treatment options for patients with Alzheimer disease.

Alzheimer disease is a progressive neurodegenerative disorder which has emerged as a major public health concern with the global population aging, and the development of effective therapeutic agents has become increasingly urgent due to its rapid increase in prevalence. There is some progress in drug development, however, the majority of new drugs have failed to demonstrate sustained clinical efficacy in large-scale trials. In addition, high costs, severe side effects have further hindered the widespread application of these therapies. This article reviews recent progress in the development of pharmacological treatments for Alzheimer disease, focusing on disease-modifying therapies targeting amyloid-β and tau proteins, also analyzes the results of phase 2 and phase 3 clinical trials of traditional and novel drugs. Future research efforts should continue to explore novel therapeutic targets and strategies to offer more effective treatment options for patients with Alzheimer disease.

Objective To observe the value of prenatal ultrasonic manifestations of congenital pulmonary airway malformation(CPAM)and bronchopulmonary sequestration(BPS)for predicting adverse outcomes of neonates.Methods Data of 51 singletons with CP AM,BPS or mixed malformations were retrospectively analyzed.The prenatal ultrasonic manifestations were observed,and the pulmonary mass volume to head circumference ratio(CVR)were measured.Receiver operating characteristic curves were drawn,the area under the curves(AUC)were calculated,and the efficacy of CVR for predicting adverse outcomes of neonates was evaluated.Results Pulmonary mass were detected in all 51 fetuses by prenatal ultrasound,with an average maximum diameter of(35.9±12.3)mm.Mediastinal displacement was observed in 28 fetuses(28/51,54.90％),pleural effusion and polyhydramnios each in 3 fetuses(3/51,5.88％),while other extrapulmonary malformations were noticed in 5 fetuses(5/51,9.80％).No fetal edema was found.According to the feeding artery of the mass,CPAM was diagnosed in 29(29/51,56.86％)fetuses,BPS in 20(20/51,39.22％),and mixed lesions were diagnosed in 2 fetuses(2/51,3.92％).The AUC of the initial CVR(CVR1),the maximum CVR(CVR2)and the last CVR(CVR3)of fetal pulmonary mass for predicting occurrence of neonatal respiratory distress and lung surgery were 0.907-0.993.CVR3≥1.25 was an independent predictive factors for neonatal respiratory distress in fetuses with pulmonary masses(OR=40.000,P=0.016).Conclusion CPAM and BPS had typical prenatal ultrasonic manifestations.CVR was a reliable indicator for predicting adverse neonatal outcomes of fetuses with CPAM and/or BPS.

A 64-year-old male patient with Parkinson′s disease received long-term use of levodopa and benserazide hydrochloride, piribedil sustained-release tablets, and selegiline. Due to involuntary twisting of head and limbs, amantadine was added and dyskinesia was relieved. Five months later, the patient felt general fatigue and weakness, and the blood sodium was 120 mmol/L. He was given sodium supplementation treatment, and the blood sodium level rose briefly and then decreased again. Excluding other factors that could cause hyponatremia, it was considered that the hyponatremia was caused by syndrome of inappropriate antidiuretic hormone secretion, which was induced by amantadine. Amantadine was stopped, sodium supplement treatment was continued, and 7 days later, the blood sodium level gradually returned to normal. After stopping sodium supplementation, fatigue and weakness did not recur, and blood sodium level did not decrease at one month of follow-up.

A 64-year-old male patient with Parkinson′s disease received long-term use of levodopa and benserazide hydrochloride, piribedil sustained-release tablets, and selegiline. Due to involuntary twisting of head and limbs, amantadine was added and dyskinesia was relieved. Five months later, the patient felt general fatigue and weakness, and the blood sodium was 120 mmol/L. He was given sodium supplementation treatment, and the blood sodium level rose briefly and then decreased again. Excluding other factors that could cause hyponatremia, it was considered that the hyponatremia was caused by syndrome of inappropriate antidiuretic hormone secretion, which was induced by amantadine. Amantadine was stopped, sodium supplement treatment was continued, and 7 days later, the blood sodium level gradually returned to normal. After stopping sodium supplementation, fatigue and weakness did not recur, and blood sodium level did not decrease at one month of follow-up.

Background: Zhongyi paste is a traditional Chinese medicine herbal paste that is externally applied to reduce inflammation and relieve pain. Methods: An acute foot swelling inflammation model in C57BL/6J mice was established by carrageenan-induced pathogenesis. Zhongyi paste raised the pain threshold and also reduced the degree of swelling in mice with carrageenan-induced foot swelling. Results: Analysis indicated that serum tumor necrosis factor-alpha, interleukin-1 beta, and prostaglandin E2 (PGE2) cytokine levels and PGE2levels in the paw tissue of the mice were decreased by Zhongyi paste treatment. The quantitative polymerase chain reaction and western blot results showed that Zhongyi paste downregulated the mRNA and protein expression of extracellular signal-regulated kinase 1/2 (ERK1/2), and cyclooxygenase-2 (COX-2), and also downregulated the mRNA expression of PGE2 . At the same time, the Zhongyi paste exerted a stronger effect as an external drug than that of indomethacin, which is an oral drug, and voltaren, which is an externally applied drug. Conclusions Our results indicated that Zhongyi paste is a very effective drug to reduce inflammatory swelling of the foot, and its mechanism of action is related to regulation of the ERK1/2–COX-2–PGE2 pathway.

Objective To investigate the clinical features,pathogenesis,diagnosis and treatment of neonatal cerebral infarction(NCI)in order to have a further understanding of its clinical features,to enhance therapeutic effica﹣cy and to improve prognosis. Methods The clinical history,head magnetic resonance imaging( MRI)+ diffusion Weighted imaging(DWI)data and folloW－up results of 39 neonates With NCI admitted into the Department of Neonato﹣logy,Gaozhou People＇s Hospital and the Second Affiliated Hospital of Shantou University Medical College from January 2013 to March 2018 Were retrospectively analyzed. Results All the 39 children Were diagnosed as NCI by MRI +DWI,among Which 30 cases(76. 92%)Were full－term infants,and 9 cases(23. 08%)Were premature infants,in Which 61. 54%(24／39 cases)Were males,and 17 cases(43. 59%)Were performed With emergency cesarean section because of umbilical cord around neck,intrauterine distress or maternal pregnancy hypertension respectively. TWenty－five patients(64. 10%)had the history of perinatal hypoxia. The presentation of MRI shoWed 32 cases(82. 10%)of ischemic cerebral infarction and 7 cases(17. 90%)of hemorrhagic cerebral infarction,While middle cerebral artery and its branches Were more susceptible to NCI With a left hemisphere predominance. Sixteen patients(41. 03%)developed convulsions. TWo patients died of purulent meningoencephalitis associated With NCI. One patient gave up treatment in the neonatal period and died 2 days after discharge. One patient died of cerebral palsy and pneumonia at the age of 11 months. Nine cases(31. 03%)developed cerebral palsy,and 2 patients developed speech disturbance so they could not express complex sentences. Conclusions Perinatal hypoxia and emergency cesarean section may be closely related to the incidence of NCI. NCI resulting from purulent meningoencephalitis is more severe and has a Worse prognosis. Considering the facts that NCI usually does not have specific clinical manifestations in the early stage,MRI +DWI,as the gold standard for the diagnosis of NCI,could be performed to facilitate early diagnosis and intervention.

Criteria for diagnosis of Alzheimer's disease (AD) is not available in China.The international criteria is not a proper choice due to issues such as translation and lead to low diagnostic rate and high rate of missed diagnosis.The research group of Alzheimer's Disease Chinese (ADC) reviewed knowledge and techniques in neuropsychology,neuroimaging,molecular biology,and clinical neurology,and systematically studied the detection techniques such as memory,language,visuospatial,executive function,and medial temporal lobe visual scores on MRI,and their optimal threshold and diagnostic value for the diagnosis of AD.Through a systematic review and consensus meeting,a diagnostic framework for screeningAD in the Chinese population was established.Among these methods,an operational standard for clinical pathology models increased the diagnostic sensitivity by 15％.The sensitivity and specificity of screening memory impairment increased by 18.1％ and 11.6％,respectively.The sensitivity of screening medialtemporal lobe atrophy increased by 24.5％ and missed diagnosis was decreased by 34.5％.An operational standard for clinical biology models,incorporating the latest molecular imaging and molecular biology techniques,has enabled the early diagnosis of AD in China.The framework combines a principled diagnostic guideline with an operational screening protocol,which is applicable to all clinical settings and of great significance for the early detection,early diagnosis and early treatment of AD.

This was a case of 32-year-old HAN woman admitted to psychiatric hospital presenting for social withdraw,deluded ideas,unexplained runaways and suicide behaviors.She was diagnosed as schizophrenia and brought to the psychiatrist for unbearable behavior problems by her family.When admitted to hospital the patient showed significant depressive symptoms and delusions with influent speech,hypotonia,involuntary movements of distal limb and ataxia.Cognitive tests revealed multiple deficits.Consulted with the neurologist,a diagnosis of organic mental disorder was suggested.Magnetic resonance imaging showed slight widen of lateral ventricles and mild atrophy of caudate nucleus and cortex of frontal lobe.The family history was re-collected and found three family members shared the influent speech and ataxia.Then the clinical diagnose of Huntingdon Disease was made and validated with gene tests.

OBJECTIVE: To analyze the effect of noise exposure on the hearing ability at different frequency in workers.METHODS: A total of 2 411 workers in a mechanical plant in Guangzhou were chosen as the study subjects by using judgment sampling method. The pure tone audiometry threshold test was carried out to analyze the status of hearing loss at different frequencies and its relationship with the length of service of workers. RESULTS: Among the 2 411 workers,883 workers had different degrees of decreased hearing thresholds,the detection rate was 36. 6%. Among them,the single unilateral hearing loss accounted for 19. 6%( 472/2 411),and the binaural hearing loss was 17. 0%( 411/2 411). The hearing loss detection rate of left ear was higher than that of the right ear( P < 0. 05). The decreased threshold of left ear at 0. 5,3. 0 and 6. 0 kHz was higher than that of the right ear at the same frequencies( P < 0. 05). The decreased threshold in both the left and the right ear increased with the increase of the frequency( P < 0. 01). The decreased hearing threshold was the highest at the frequency of 6. 0 kHz. The auditory threshold of left ear in 0. 5,1. 0,2. 0,3. 0 and 6. 0 kHz were higher than that of right ear at the same frequencies( P < 0. 05). The detection rate of hearing loss increased with the increase of service length( P < 0. 01). The decreased threshold of 1. 0-6. 0 kHz increased with the increased length of service except for the frequency of 0. 5 kHz( P < 0. 05). CONCLUSION: There is a significant decreased threshold in workers exposed to noise frequency of 6. 0 kHz. The hearing ability of left ear is more easily impaired than the right ear.There is a dose-response relationship for the length of noise exposure and hearing loss.