With the intensification of population aging， the proportion of people with dementia in our country is rising sharply， bringing a heavy economic and caregiving burden to families and society. Alzheimer's disease （AD） is a spectrum of progressive cognitive impairment disorders that onset in old age， characterized by memory decline， reduced attention and executive function， and in the late stages of the disease， it can even progress to dementia， ultimately leading to the loss of self-care abilities and further increasing the pressure on families and society. Patients with Alzheimer's disease （AD） can be in a preclinical stage for decades without obvious clinical cognitive decline， but significant pathological changes have already occurred in the brain， including the aggregation of beta-amyloid （Aβ） to form senile plaques， the hyperphosphorylation and aggregation of tau protein to form neurofibrillary tangles， vascular amyloid deposition， synaptic and neuronal loss， as well as neuroinflammation. This stage represents the best opportunity for early intervention in AD. Accurate diagnosis or prediction of AD risk and implementation of intervention measures can significantly delay or prevent the progression of AD. In recent years， the application of various tracers that track the neuropathological changes of AD in PET/CT has led to significant progress in clinical research on the imaging diagnosis， treatment monitoring， and prognostic prediction of preclinical and early-stage AD. This article will review the application of PET/CT and PET/MR techniques marked with Aβ， tau protein， fluorodeoxyglucose （FDG）， synaptic， and inflammatory tracers in the early diagnosis， differential diagnosis， disease staging， treatment monitoring， and prognostic prediction of AD， and compare the relative utility and limitations of these tracers as biomarkers， providing a basis and reference for clinicians to choose appropriate PET markers in the research of early diagnosis and treatment of preclinical AD and early-stage AD.

Objective:To assess the association between body mass index (BMI) and major adverse cardiovascular and cerebrovascular events (MACCE) among patients with acute coronary syndrome (ACS).Methods:This was a multicenter prospective cohort study, which was based on the Improving Care for Cardiovascular Disease in China (CCC) project. The hospitalized patients with ACS aged between 18 and 80 years, registered in CCC project from November 1, 2014 to December 31, 2019 were included. The included patients were categorized into four groups based on their BMI at the time of admission: underweight (BMI<18.5 kg/m 2), normal weight (BMI between 18.5 and 24.9 kg/m 2), overweight (BMI between 25.0 and 29.9 kg/m 2), and obese (BMI≥30.0 kg/m 2). Multivariate logistic regression models was used to analyze the relationship between BMI and the risk of in-hospital MACCE. Results:A total of 71 681 ACS inpatients were included in the study. The age was (63.4±14.7) years, and 26.5% (18 979/71 681) were female. And the incidence of MACCE for the underweight, normal weight, overweight, and obese groups were 14.9% (322/2 154), 9.5% (3 997/41 960), 7.9% (1 908/24 140) and 7.0% (240/3 427), respectively ( P<0.001). Multivariate logistic regression analysis showed a higher incidence of MACCE in the underweight group compared to the normal weight group ( OR=1.30, 95% CI 1.13-1.49, P<0.001), while the overweight and obese groups exhibited no statistically significant difference in the incidence of MACCE compared to the normal weight group (both P>0.05). Conclusion:ACS patients with BMI below normal have a higher risk of in-hospital MACCE, suggesting that BMI may be an indicator for evaluating short-term prognosis in ACS patients.

Myocardial fibrosis （MF） is a prevalent pathological process in a spectrum of cardiac conditions， including myocardial infarction， hypertensive heart disease， and dilated cardiomyopathy. It is marked by an overabundance of extracellular matrix deposition， diminished myocardial compliance， and impaired cardiac function， which can lead to arrhythmias and sudden cardiac death. The current therapeutic approach primarily aims to suppress the progression of fibrosis， yet the therapeutic outcomes are poor. The pathogenesis of MF involves multiple signaling pathways， including the transforming growth factor-beta （TGF-β）/Smads signaling pathway， nuclear factor-kappa B （NF-κB） signaling pathway， phosphoinositide 3-kinase （PI3K）/protein kinase B （Akt） signaling pathway， and mitogen-activated protein kinase （MAPK） signaling pathway. Traditional Chinese medicine （TCM） boasts a rich history in the treatment of cardiovascular diseases， offering distinctive benefits such as minimal side effects and high safety， and it has demonstrated promising therapeutic effects in the treatment of MF. In recent years， research has turned its attention to the application of TCM in modulating the signaling pathways associated with MF. It has been demonstrated that TCM can modulate the MF-related signaling pathways to exert anti-inflammatory effects， regulate cellular autophagy， cell proliferation， and apoptosis， reduce myocardial oxidative stress and damage， and inhibit the activation of fibroblasts and collagen synthesis， thereby exhibiting the potential to mitigate or even reverse the progression of MF. Experimental research and clinical observations indicate that TCM formulas such as Yixin Futing decoction， Luhong prescription， Zhilong Huoxue Tongyu capsules， and Kangjian Yixin prescription can effectively ameliorate MF and enhance cardiac function through the multi-component regulation of multiple cellular pathways. Specific TCM constituents， including isoliquiritigenin and astragaloside， have been shown to inhibit the expression of TGF-β₁， thereby disrupting the Smad signaling pathway. Compounds like glycyrrhizic acid and allicin can suppress the NF-κB signaling pathway and curtail collagen synthesis in myocardial cells， and forsythoside can activate the PI3K/Akt signaling pathway， contributing to its anti-fibrotic effects.

Objective:To study the quality and stability of commercial ready-to-use tryptone soya agar(TSA)after storing at 2-25 ℃ for different storage duration under dark condition in order to discuss a determination method of validity period for medium.Methods:Three consecutive batches of ready-to-use TSA medium from two manufac-turers were selected and stored at 2-25 ℃ under dark conditions for 30,90 and 180 days,respectively.The appearance,pH,medium suitability and sterility of the medium were tested.Results:The results of appearance,pH,suitability and sterility of TSA medium from two manufacturers for each batch under different storage duration all met the requirements of the Chinese Pharmacopoeia 2020 Volume IV on the quality control of medium.Conclusion:The TSA medium from two manufacturers all met the requirements when stored for 180 days at 2-25 ℃ under dark condition,indicating that the validity period of TSA medium from two manufacturers can reach 180 days.

Production of chiral amines and unnatural amino-acid using ω-transaminase can be achieved by kinetic resolution and asymmetric synthesis, thus ω-transaminase is of great importance in the synthesis of pharmaceutical intermediates. By genomic data mining, a putative ω-transaminase gene hbp was found in Burkholderia phytofirmans PsJN. The gene was cloned and over-expressed in Escherichia coli BL21 (DE3). The recombinant enzyme (HBP) was purified by Ni-NTA column and its catalytic properties and substrate profile were studied. HBP showed high relative activity (33.80 U/mg) and enantioselectivity toward β-phenylalanine (β-Phe). The optimal reaction temperature and pH were 40 ℃ and 8.0-8.5, respectively. We also established a simpler and more effective method to detect the deamination reaction of β-Phe by UV absorption method using microplate reader, and demonstrated the thermodynamic property of this reaction. The substrate profiling showed that HBP was specific to β-Phe and its derivatives as the amino donor. HBP catalyzed the resolution of rac-β-Phe and its derivatives, the products (R)-amino acids were obtained with about 50% conversions and 99% ee.
Bacterial Proteins ; biosynthesis ; genetics ; Burkholderia ; enzymology ; Cloning, Molecular ; Escherichia coli ; genetics ; metabolism ; Transaminases ; biosynthesis ; genetics

Objective To explore the relationship between G-protein β3 subunit (GNB3) gene C825T polymor?phism and the weight gain of schizophrenics treated with olanzapine. Methods Ninety schizophrenics of first time hospi?talization were collected and treated with olanzapine for 12 weeks. The changes of body weight and body mass index (BMI) were detected before and after 12-week olanzapine treatment. The GNB3 gene C825T polymorphism in patients was determined by polymerase chain reaction (PCR) and DNA sequencing technique. The correlation of GNB3 gene C825T polymorphism and change of clinical parameters was analyzed. Results Body weight and BMI in patients were all increased significantly after treatment (all P<0.01). Weight gain rate (WGR) and increase of BMI in the TT genotype group were higher than those in the CC genotype group (all P<0.01). WGR and increase of BMI in the T-allele carrier (TT and CT genotypes) were higher than those in the T-allele non-carrier (CC genotype) (all P<0.01). There was signifi?cant difference in distribution of genotypes between WGR ≥7% group (CC 15.69%, CT 54.90%, TT 29.41%) and WGR <7% group (CC 38.46%, CT 43.59%, TT 17.95%) (P<0.05). The frequency of T-allele in the WGR≥7% group (63.33%) was higher than that in the WGR<7%group (39.74%) (P<0.05). Multi-variable linear regression indicated that TT genotype (contrasted with CC genotype) was an influential factor for change of body weight after treatment with olan?zapine (β=1.83, standardized β=0.29, P<0.01). Conclusions The GNB3 gene C825T polymorphism is associated with olanzapine-induced weight gain.

Objective To investigate the efficiency of the modified posterolateral curved incision with double intermuscular approach in the treatment of posterolateral tibial plateau fractures.Methods From August 2009 to March 2013,15 men and 17 women aged 28 to 77 (mean,46.25) years with posterolateral spitting or collapse tibial plateau fractures were treated to undergo a modified posterolateral approach.All types of fractures were closed,without nerve or artery injury.The duration from injury to fixation was 3-18 (mean,7.13) days.The modified posterolateral approach was preformed to expose tibial anterolateral condyle and posterolateral condyle through intermuscular space of anterior tibial muscle,popliteus muscle and soleus muscle.After open reduction,anterolateral fractures and posterolateral fractures were fixed by the T-shaped plate and Golf shaped plate respectively.Results All of the 32 patients were followed up from 6 months to 36 months (in average of 15.3 months).Postoperative X-ray showed satisfied fractures without obvious collapse of the articular surface.At the last follow-up,the Rasmussen scores were range from 6 to 18 (in average of 14.06),namely 14 cases excellent,15 cases good,3 cases fair.The knee joint functions were evaluated according to HSS.The HSS results showed that there were 12 cases excellent,16 cases good,3 cases fair and 1 case bad.None of the cases suffered from injuries of crucial blood vessel or nerves.No incision necrosis,wound infection or fixation failure occurred during follow-up.Conclusion Open reduction and internal fixation via modified posterolateral approach can expose posterolateral and anterolateral tibial plateau fracture in one incision.Fibular head osteotomy can be avoided.The present approach could also reduce surgical injury,minimize the possibilities of incision necrosis or plate exposure.The modified posterolateral approach can be recommended in clinical practice.

We produced (S)-4-cyano-3-(4-chlorophenyl)-butyrate by highly stereoselective biocatalyst in this study. A nitrilase-producing strain, named Gibberella intermedia WX12, was isolated by 3-(4-chlorophenyl)-glutaronitrile as substrate in the screening with phenol-sodium hypochlorite method. The fermentation conditions and catalytic properties of this strain were investigated. The preferred carbon and nitrogen sources for nitrilase production were lactose (30 g/L) and peptone (20 g/L). After being cultivated for 96 h, the cells were collected for use in biotransformation. The hydrolysis of 3-(4-chlorophenyl)-glutaronitrile was performed at 30 degrees C in phosphate buffer (pH 8.0, 50 mmol/L) for 24 h to give (S)-4-cyano-3-(4-chlorophenyl)-butyric acid with 90% yield and > 99% of ee, which can be used for the synthesis of (R)- and (S)-baclofen. The configuration of product was determined by chemically converting it to baclofen and comparison with the authentic sample by chiral HPLC analysis.
Aminohydrolases ; metabolism ; Baclofen ; chemical synthesis ; chemistry ; Biocatalysis ; Chlorophenols ; chemistry ; Gibberella ; enzymology ; Hydrolysis ; Nitriles ; chemistry ; Prodrugs ; chemical synthesis ; chemistry