Clinical study of modified suspension reduction method combined with percutaneous vertebroplasty in the treatment of thoracolumbar osteoporotic compression fracture / 中国骨伤

OBJECTIVE@#To investigate the clinical effect of modified suspension reduction method combined with percutaneous vertebroplasty in the treatment of osteoporotic thoracolumbar compression fractures.@*METHODS@#From February 2020 to October 2021, 92 patients with thoracolumbar osteoporotic compression fracture were treated by percutaneous vertebroplasty. According to different treatment methods, they were divided into the observation group and the control group. The observation group was treated with modified suspension reduction and then percutaneous vertebroplasty, while the control group was treated with percutaneous vertebroplasty alone. The observation group (47 cases), including 20 males and 27 females, the age ranged from 59 to 76 years old with an average of (69.74±4.50) years old, fractured vertebral bodies:T10(2 cases), T11(7 cases), T12(19 cases), L1(14 cases), L2(5 cases);the control group(45 cases), including 21 males and 24 females, the age ranged from 61 to 78 years old with an average of (71.02±3.58) years old, fractured vertebral bodies:T10(3 cases), T11(8 cases), T12(17 cases), L1(12 cases), L2(5 cases);The leakage of bone cement were observed, the visual analogue scale (VAS), Oswestry lumbar dysfunction index (ODI), anterior vertebrae height (AVH), Cobb angle of kyphosis and the amount of bone cement injected before and after operation were recorded and compared between the two groups.@*RESULTS@#All patients were followed up, ranged from 6 to10 with an average of (8.45±1.73) months. Two patients ocurred bone cement leakage in observation group and 3 patients in control group. AVH of observation group increased (P<0.05) and Cobb angle of injured vertebrae decreased (P<0.05). Cobb angle of injured vertebrae and AVH of the control group were not significantly changed (P>0.05). Cobb angle of injured vertebrae of the observation group was lower than that of control group (P<0.05) and AVH was higher than that of the control group (P<0.05). In the observation group, VAS before operation and 1 week, 3 and 6 months after operation respectively were(7.32±1.05) scores, (3.56±1.18) scores, (1.83±0.67) scores, (1.27±0.34) scores, and ODI were(40.12±14.69) scores, (23.76±10.19) scores, (20.15±6.39) scores, (13.45±3.46) scores. In the control group, VAS before operation and 1 week, 3 and 6 months after operation respectively were(7.11±5.26) scores, (3.82±0.68) scores, (1.94±0.88) scores, (1.36±0.52) scores, and ODI were(41.38±10.23) scores, (25.13±14.22) scores , (20.61±5.82) scores, (14.55±5.27) scores . The scores of VAS and ODI after operation were lower than those before operation (P<0.05), but there was no significant difference between the two groups (P<0.05).@*CONCLUSION@#Modified suspension reduction method combined with PVP surgery for osteoporotic thoracolumbar compression fractures has achieved good clinical results, which can effectively relieve lumbar back pain, restore vertebral height, correct kyphosis, improve lumbar function and patients' quality of life.

Effects of warm acupuncture on post-stroke cognitive impairment based on the theory of intestinal flora / 国际中医中药杂志

Objective:To observe the effects of warm acupuncture on post-stroke cognitive impairment (PSCI) based on the theory of intestinal flora.Methods:A randomized controlled trial was conducted. 60 patients with PSCI in the Department of Acupuncture and Neurology of the First Affiliated Hospital of Xinjiang Medical University from October 2020 to June 2022 were selected as the observation objects, and were divided into 2 groups by random number table, with 30 cases in each group. On the basis of cognitive rehabilitation training, the treatment group was given warm acupuncture treatment, and the control group was given routine acupuncture treatment. 2 groups were treated for 4 weeks as 1 course, and a total of 4 courses were treated. Montreal cognitive assessment (MoCA) was used to assess patients' cognitive function before and after treatment, and mini-mental state examination (MMSE) was used to assess patients' intelligence level. The numbers of bifidobacteria and lactic acid bacteria in fecal samples were calculated, and plasma gamma-aminobutyric acid (GABA) levels were detected by ELISA to evaluate the clinical efficacy.Results:During the study, 1 case was lost in each of the two groups, and finally 29 cases were included in the curative effect statistics. The total effective rate was 79.3% (23/29) in the treatment group and 65.5% (19/29) in the control group, with statistical significance ( χ2=43.39， P<0.05). After treatment, MoCA score [(24.23±1.36) vs. (21.26±1.30), t=3.12] and MMSE score [(25.35±1.24) vs. (21.52±1.22), t=3.25] in the treatment group were higher than those in the control group ( P<0.05); Bifidobacterium [(9.20±1.25) LgCFU/g vs. (7.23±1.21) LgCFU/g, t=2.98], Lactic acid bacteria [(8.24±1.12) LgCFU/g vs. (6.25±1.22) LgCFU/g, t=2.92], and the level of GABA [(283.80±83.54) mmol/L vs. (264.76±61.38) mmol/L, t=10.54] were higher than those in the control group ( P<0.05 or P<0.01). Conclusion:Warm acupuncture and moxibustion can effectively regulate the number of intestinal beneficial bacteria in PSCI patients, increase the level of GABA, promote brain tissue repair and improve cognitive function.

Protective effect and mechanism of acellular nerve allografts combined with electroacupuncture on spinal ganglia in rats with sciatic nerve injury / 解剖学报

Objective To investigate the protective effect and mechanism of acellular nerve allografts(ANA)combined with electroacupuncture on spinal ganglia in rats with sciatic nerve injury(SNI).Methods Totally 50 male adult SD rats were randomly selected for this experiment.Ten rats were prepared for the ANA.Forty male SD rats were randomly divided into normal group,model group,ANA group and combinational group,with 10 rats in each group.The SNI model was established by cutting off the nerves 10 mm at the 5 mm on the inferior border of piriformis after separating the right sciatic nerves.The rats in the ANA group were bridged with ANA to the two broken ends of injured nerves.The rats in the combinational group were treated with electroacupuncture 2 days after ANA bridging,Huantiao(GB30)and Yanglingquan(GB34)were performed as the acupuncture points,each electroacupuncture lasted 15 minutes and 7 days as a course of treatment,4 courses in all.Sciatic nerve conduction velocity was measured by electrophysiology to evaluate the regeneration of damaged axons.Morphology of spinal ganglia was observed by Nissl staining.The expression of nerve growth factor(NGF)and brain-derived neurotrophic factor(BDNF)were detected by Western blotting and immunofluorescent staining.Results Compared with the normal group,the sciatic nerve conduction velocity in model group decreased significantly(P<0.01),Nissl bodies in neurons of spinal ganglia were swollen and dissolved,with incomplete structure and the number decreased dramatically(P<0.01),while the level of NGF and BDNF also decreased significantly(P<0.01).Compared with the model group,the sciatic nerve conduction velocity in ANA and combinational groups strongly increased(P<0.01),the damage of Nissl bodies in neurons of spinal ganglia reduced and the number obviously increased(P<0.01),the level of NGF and BDNF increased considerably(P<0.01).Compared with the ANA group,the sciatic nerve conduction velocity in combinational group increased significantly(P<0.01),the morphology of Nissl bodies in neurons of spinal ganglia were more regular and the number increased(P<0.01),moreover,the level of NGF also increased significantly(P<0.01).Conclusion ANA combined with electroacupuncture can enhance the sciatic nerve conduction velocity,improve the morphology of neurons in spinal ganglia and play a protective effect on spinal ganglia.The mechanism can be related to the higher expression of NGF and BDNF proteins,especially the expression of NGF protein.

Variation in renal function of type 2 diabetic rats undergoing aerobic exercise / 中国组织工程研究

BACKGROUND:Type 2 diabetes is often accompanied by renal dysfunction.Increasing studies have shown that exercise can alleviate metabolic disorders and renal dysfunction in diabetic patients.However,the specific mechanism underlying the renal protective effect of exercise in patients with type 2 diabetes is rarely reported. OBJECTIVE:To investigate whether aerobic exercise can improve renal function in type 2 diabetic rats by inhibiting transforming growth factor β1/Notch1 pathway. METHODS:Male Sprague-Dawley rats were randomly divided into normal control group and diabetes model group.After successful modeling,they were randomly divided into diabetes control group and diabetes exercise group.Rats in the diabetes exercise group were subjected to an 8-week aerobic exercise.Samples were collected after exercise,and the relevant indexes of glucose and lipid metabolism and renal function were detected by automatic biochemical analyzer and ELISA.The microscopic structure of renal cortex was observed by electron microscope.ELISA and RT-PCR were used to detect the expression of related proteins and genes in rat kidney tissue. RESULTS AND CONCLUSION:Compared with the normal control group,fasting blood glucose,total cholesterol,and triglyceride levels and insulin resistance index were significantly increased in the diabetic control group(P＜0.05).Aerobic exercise could significantly reduce fasting blood glucose and triglyceride levels(P＜0.05).Compared with the normal control group,the diabetic control group had significantly increased contents of urinary microalbumin,serum urea nitrogen and serum creatinine(P＜0.01),thickened renal basement membrane,mesangial matrix hyperplasia,accompanied by a certain degree of foot process fusion,and obvious lesion of the kidney.Aerobic exercise could significantly down-regulate the overexpressions of urinary microalbumin,serum urea nitrogen and serum creatinine in type 2 diabetic rats(P＜0.01),and significantly improve the pathological changes of the kidney in diabetic rats.Compared with the normal control group,the protein and gene expression levels of transforming growth factor β1,Notch1,Jagged1 and Hes1 in rat kidney tissue were significantly increased in the diabetic control group(P＜0.01).Aerobic exercise had a highly significant inhibitory effect on the overexpression of transforming growth factor β1,Notch1 and Jagged1 proteins and genes(P＜0.01)and also significantly inhibited the overexpression of Hes1 protein(P＜0.05).In conclusion,aerobic exercise can protect renal function and delay the pathological progression of the kidney in diabetic rats,which may be achieved by inhibiting the overexpression of transforming growth factor β1/Notch1 signaling pathway.

Clinical characteristics of nephrocalcinosis in preterm infants / 中国新生儿科杂志

Objective:To study the clinical characteristics and risk factors of nephrocalcinosis in preterm infants.Methods:From March 2021 to August 2021, all preterm infants admitted to NICU of our hospital were retrospectively analyzed. The infants were assigned into nephrocalcinosis group and non-nephrocalcinosis group according to urinary tract ultrasound. Clinical data including gestational age, birth weight(BW), nutritional support strategy and complications were reviewed.Results:A total of 40 preterm infants (<34 weeks) were enrolled. 9 cases were in the nephrocalcinosis group and 31 cases in the non-nephrocalcinosis group. The nephrocalcinosis group had lower BW[(1 167±214) g vs.(1 586±215) g], higher calcium [6.9 (5.1, 8.7) g vs.3.3 (2.1, 6.8) g] and vitamin D intake [3.2(2.5, 4.2)×10 4U vs.1.7(1.1, 3.2)×10 4U] during hospitalization. No significant differences existed between the two groups on the following items:blood calcium and phosphate, 25-hydroxyvitamin D, feeding strategy, time to reach full enteral feeding(TFF), furosemide dosage and respiratory support duration ( P>0.05). In the nephrocalcinosis group, the median age of diagnosing nephrocalcinosis was 40.0(30.0, 52.5)d after birth. 5 cases showed bilateral nephrocalcinosis. 5 cases in the nephrocalcinosis group received renal tubule function examination,4 cases had increased urine β2 microglobulin and 2 cases had increased urine α1 microglobulin. 7 cases had elevated urine calcium in the nephrocalcinosis group. Follow-up showed that nephrocalcinosis disappeared 3-9 months after birth. Conclusions:BW, total calcium and vitamin D intake are risk factors for nephrocalcinosis in preterm infants. Increased urine β2 microglobulin and calcium levels are common co-morbidities in preterm infants with nephrocalcinosis.

Multi-level ranking classification algorithm for nuclear cataract based on AS-OCT image / 中华实验眼科杂志

Objective:To investigate the diagnostic value of an intelligent assisted grading algorithm for nuclear cataract using anterior segment optical coherence tomography (AS-OCT) images.Methods:A diagnostic test study was conducted.AS-OCT image data were collected from 939 cases of 1 608 eyes of nuclear cataract patients at the Shanghai Tenth People's Hospital of Tongji University from November 2020 to September 2021.The data were obtained from the electronic case system and met the requirements for clinical reading clarity.Among them, there were 398 cases of 664 male eyes and 541 cases of 944 female eyes.The ages of the patients ranged from 18 to 94 years, with a mean age of (65.7±18.6) years.The AS-OCT images were labelled manually from one to six levels according to the Lens Opacities Classification System Ⅲ (LOCS Ⅲ grading system) by three experienced clinicians.This study proposed a global-local cataract grading algorithm based on multi-level ranking, which contains five basic binary classification global local network (GL-Net).Each GL-Net aggregates multi-scale information, including the cataract nucleus region and original image, for nuclear cataract grading.Based on ablation test and model comparison test, the model's performance was evaluated using accuracy, precision, sensitivity, F1 and Kappa, and all results were cross-validated by five-fold.This study adhered to the Declaration of Helsinjki and was approrved by Shanghai Tenth People's Hospital of Tongji University (No.21K216).Results:The model achieved the results with an accuracy of 87.81%, precision of 88.88%, sensitivity of 88.33%, F1 of 88.51%, and Kappa of 85.22% on the cataract dataset.The ablation experiments demonstrated that ResNet18 combining local and global features for multi-level ranking classification improved the accuracy, recall, specificity, F1, and Kappa metrics.Compared with ResNet34, VGG16, Ranking-CNN, MRF-Net models, the performance index of this model were improved.Conclusions:The deep learning-based AS-OCT nuclear cataract image multi-level ranking classification algorithm demonstrates high accuracy in grading cataracts.This algorithm may help ophthalmologists in improving the diagnostic accuracy and efficiency of nuclear cataract.

Application progress of artificial intelligence in keratoconus / 国际眼科杂志(Guoji Yanke Zazhi)

Keratoconus is a blinding corneal disease that is particularly prevalent among adolescents. Early diagnosis and treatment can significantly reduce visual impairment in advanced stages and improve its prognosis. Based on machine learning and deep learning in keratoconus, Artificial intelligence(AI)mainly involves early screening and diagnosis, severity grading, progression prediction, and outcomes prediction. In this paper, the main applications and research progress of AI in keratoconus in recent years were summarized, and the challenges and future prospects in this field were discussed.

Effect of type of carrier material on the in vitro properties of solid dispersions of progesterone / 药学学报

This study investigated the effect of different carrier materials on the in vitro properties of progesterone solid dispersions. The solid dispersions of the insoluble drug progesterone were prepared by hot melt extrusion technique using rheological properties as the index of investigation, and the in vitro properties of the solid dispersions were characterized. Scanning electron microscope revealed solid dispersions with rough surfaces and agglomerated microstructures into irregular lumpy particles. Differential scanning calorimetry and powder X-ray diffraction showed the change of progesterone crystalline form in solid dispersions from crystalline to amorphous state. In vitro dissolution studies showed that solid dispersions prepared with different carrier materials can effectively improve the dissolution rate of drugs. The results of the study showed that the type of carrier material had a significant effect on the in vitro properties of solid dispersions, providing a reference for the study of solid dispersions in the controlled release of insoluble drugs.

A comparative study of different surgical method for stage ⅠA non-small cell lung cancer / 局解手术学杂志

Objective To compare the clinical efficacies of video-assisted thoracoscopic segmentectomy versus lobectomy for early-stage non-small cell lung cancer.Methods The clinical data of 234 patients with stage ⅠA non-small cell lung cancer and undergoing different surgical methods under video-assisted thoracoscopy admitted to Chongqing Dianjiang General Hospital were retrospectively analyzed,and the patients were divided into the lung segment group and the lung lobe group according to their surgical methods.The clinical characteristics of the patients in the two groups were balanced by a 1-to-1 ratio matching through the propensity score matching method,and each group finally included 63 cases.The perioperative indicators containing operation time,intraoperative blood loss,postoperative thoracic drainage tube indwelling time,thoracic drainage volumes 24 hours and 48 hours after operation and postoperative hospital stay were compared of patients between the two groups.The incidence of postoperative complications such as air leakage>6 days,pulmonary infection,atelectasis,hemoptysis,and hoarseness in the two groups was collected.Results There was no significant difference in the operation time,intraoperative blood loss,thoracic drainage volumes 24 hours and 48 hours after operation,postoperative thoracic drainage tube indwelling time or incidence of postoperative complications of patients between the two groups(P>0.05).The postoperative hospital stay of patients in the lung segment group was shorter than that in the lung lobe group,with statistically significant difference(P=0.003).Conclusion For patients with stage ⅠA non-small cell lung cancer,video-assisted thoracoscopic segmentectomy has similar perioperative efficacy to lobectomy,while segmentectomy has a more significant advantage in shortening the hospital stay.

Key gene screening and prediction model construction of gastric cancer based on machine learning / 中国医学物理学杂志

Objective To verify the genetic characteristics associated with gastric cancer,and to propose a hybrid feature selection method for identifying target genes,further analyzing their significance and establishing a new diagnostic prediction model.Methods Analysis of variance in bioinformatics was performed on the original gastric cancer data,and then machine learning methods such as random forest,recursive feature elimination of support vector machine,and LASSO algorithm were used to screen gastric cancer associated genes,and the intersection of results was taken as the key gene set.The key genes were identified and verified through enrichment analysis.The diagnosis and prediction models based on 8 kinds of machine learning classification algorithms such as multi-layer perceptron,logistic regression and decision tree,were constructed using the key genes.Results The key genes selected by the hybrid feature selection method were closely related to the tumorigenesis and development.Eight key genes(TXNDC5,BMP8A,ONECUT2,COL10A1,JCHAIN,INHBA,LCTL and TRIM59)were identified as potential markers of good diagnostic efficacy in gastric cancer.The ROC curve and accuracy results demonstrated that among the 8 classification models,MLP is the best gastric cancer prediction model,with an accuracy of 97.77%,which was 3.83%higher than that of Xgboost gastric cancer prediction model.Conclusion The study identifies 8 key genes for the diagnosis and prevention of gastric cancer,and establishes the optimal prognosis model.

Review on application of artificial intelligence in tumor gene expression data analysis / 中国医学物理学杂志

Tumors are serious diseases threatening human health,and the early diagnosis is essential to improve treatment success and patient survival.The study of tumor gene expression data has become a major tool for revealing tumor disease mechanisms,in which artificial intelligence plays an important role.The potential advantages of supervised learning,unsupervised learning and deep learning in tumor prediction and classification are explored from the perspective of machine learning methods.Special attention is paid to the impact of feature selection algorithms on gene screening and their importance in high-dimensional gene expression data.By providing a comprehensive overview of the application and development of artificial intelligence in the analysis of tumor gene expression data,the study aims to provide an outlook for future research directions and promote further development.

A Research on data-driven operation and maintenance management mode of large-scale medical imaging equipment / 中国医学装备

Objective:To build a data-driven operation and maintenance management model for large-scale medical imaging equipment,and to analyze its application value in medical equipment management.Methods:The data-driven operation and maintenance management mode of large-scale medical imaging equipment was composed of operation and maintenance management mode architecture,equipment health status monitoring management platform architecture,historical data fault diagnosis model architecture and operation and maintenance management.16 medical imaging equipment in clinical use in Chengdu Public Health Clinical Medical Center from January 2020 to February 2022 were selected,and the traditional medical imaging equipment operation and maintenance management mode(referred to as traditional mode)and data-driven large-scale medical imaging equipment operation and maintenance management mode(referred to as data-driven mode)were adopted respectively for management according to different management modes.The imaging effect of equipment image,the frequency of equipment failure,the cost effectiveness of equipment and the satisfaction score of equipment management personnel were compared between the two management modes.Results:The scores of accuracy of diagnosis results,accuracy of patient information,image position qualification rate,image clarity,image pass rate,image quality rate and total image imaging score of the data-driven model were(9.78±1.25)points,(9.88±1.11)points,(9.54±1.08)points,(9.66±1.27)points and(9.83±1.43)points,(9.86±1.63)points and(58.55±1.44)points,respectively,which were higher than those in the traditional mode,the difference was statistically significant(t=4.958,5.268,6.522,4.327,9.765,3.923,21.474,P<0.05).The self-repair and human-made failures occurred 22 times and 10 times respectively in the data-driven model,which were lower than those of the traditional model,and 24 times of long-term use faults,which was higher than that of the traditional model,the difference was statistically significant(x2=4.363,4.294,18.692,P<0.05).The satisfaction scores of radiologists,equipment maintenance personnel,imaging technicians and patients with the data-driven mode were(94.52±6.15)points,(91.19±5.35)points,(89.27±4.93)points and(92.24±5.51)points,respectively,which were higher than those of the traditional mode,the difference was statistically significant(t=6.504,5.534,6.821,9.556,P<0.05).Conclusion:The operation and maintenance management mode based on data driven of large medical imaging equipment can improve the imaging quality of imaging equipment,reduce the incidence of failure,reduce equipment maintenance and maintenance costs,and improve user satisfaction.

Application of CDO1 Gene Promoter Methylation in Tumors / 生物化学与生物物理进展

Cysteine dioxygenase 1 (CDO1) gene is a non-heme structured, iron-containing metalloenzyme involved in the conversion of cysteine to cysteine sulfinic acid to regulate cysteine accumulation in vivo. Elevated levels of cysteine have been shown to be cytotoxic and neurotoxic, and this is the first important step in the breakdown of cysteine metabolism in mammalian tissues. The human CDO1 gene is located on chromosome 5q23.2. Studies have shown that deletion or epigenetic silencing of this chromosomal region contributes to tumorigenesis. It is highly expressed in the liver and placenta, and weakly in the heart, brain and pancreas. CDO1 is a tumor suppressor gene (TSG) with a wide range of functions, which can be involved in various biological processes such as tumor cell proliferation, differentiation, apoptosis and iron death, thus affecting the tumor development. CDO1 is epigenetically regulated in human cancers, compared to normal tissues. The CDO1’s mRNA or protein expression levels were significantly down-regulated in tumor tissues, whereas promoter DNA methylation of the CDO1 gene usually accumulates with the progression of human cancers. Aberrant hypermethylation on the CDO1 promoter is a common event in tumor cells, which leads to transcriptional inactivation and silencing of the CDO1 gene. High frequency of methylation of CDO1 gene promoter methylation region in a variety of tumors including breast, oesophageal, lung, bladder, gastric and colorectal cancers. CDO1 gene promoter methylation levels reflect cancer progression and malignant tumorigenesis, which is a common molecular indicator explaining poor prognosis in human cancers. Treatment with 5-aza-2′-deoxycytidine (a drug that promotes demethylation) reactivated the CDO1 expression in most cancer cell lines, indicating that the transcriptional expression of CDO1 is closely correlated with its promoter methylation level, CDO1 gene promoter methylation and tumor progression have also received increasing attention from researchers. It was found that CDO1 gene promoter hypermethylation can be used as an early tumor marker for clinical aid diagnosis and helps to differentiate cancerous from benign diseases. It was also found that CDO1 promoter DNA methylation showed reliable tumor monitoring potential in human body fluids, and furthermore, the degree of CDO1 promoter methylation was strongly correlated with resistance to chemotherapy with tumor drugs, which would be helpful in evaluating the efficacy of chemotherapeutic drugs. Thus, CDO1, a common promoter methylation gene in human cancers, is closely associated with the development of a wide range of tumors and is one of the most promising candidate genes for assessing tumor-specific epigenetic changes. This article reviews the biological functions of CDO1 and its promoter DNA methylation in tumors, focusing on the mechanism of CDO1 DNA promoter methylation in tumors, with a view to providing theoretical guidance for the clinical diagnosis and treatment of tumors with CDO1 as a potential therapeutic target.

Application Study of Enzyme Inhibitors and Their Conformational Optimization in The Treatment of Alzheimer’s Disease / 生物化学与生物物理进展

Alzheimer’s disease (AD) is a central neurodegenerative disease characterized by progressive cognitive dysfunction and behavioral impairment, and there is a lack of effective drugs to treat AD clinically. Existing medications for the treatment of AD, such as Tacrine, Donepezil, Rivastigmine, and Aducanumab, only serve to delay symptoms and but not cure disease. To add insult to injury, these medications are associated with very serious adverse effects. Therefore, it is urgent to explore effective therapeutic drugs for AD. Recently, studies have shown that a variety of enzyme inhibitors, such as cholinesterase inhibitors, monoamine oxidase (MAO)inhibitors, secretase inhibitors, can ameliorate cholinergic system dysfunction, Aβ production and deposition, Tau protein hyperphosphorylation, oxidative stress damage, and the decline of synaptic plasticity, thereby improving AD symptoms and cognitive function. Some plant extracts from natural sources, such as Umbelliferone, Aaptamine, Medha Plus, have the ability to inhibit cholinesterase activity and act to improve learning and cognition. Isochromanone derivatives incorporating the donepezil pharmacophore bind to the catalytic active site (CAS) and peripheral anionic site (PAS) sites of acetylcholinesterase (AChE), which can inhibit AChE activity and ameliorate cholinergic system disorders. A compound called Rosmarinic acid which is found in the Lamiaceae can inhibit monoamine oxidase, increase monoamine levels in the brain, and reduce Aβ deposition. Compounds obtained by hybridization of coumarin derivatives and hydroxypyridinones can inhibit MAO-B activity and attenuate oxidative stress damage. Quinoline derivatives which inhibit the activation of AChE and MAO-B can reduce Aβ burden and promote learning and memory of mice. The compound derived from the combination of propargyl and tacrine retains the inhibitory capacity of tacrine towards cholinesterase, and also inhibits the activity of MAO by binding to the FAD cofactor of monoamine oxidase. A series of hybrids, obtained by an amide linker of chromone in combine with the benzylpiperidine moieties of donepezil, have a favorable safety profile of both cholinesterase and monoamine oxidase inhibitory activity. Single domain antibodies (such as AAV-VHH) targeted the inhibition of BACE1 can reduce Aβ production and deposition as well as the levels of inflammatory cells, which ultimately improve synaptic plasticity. 3-O-trans-p-coumaroyl maslinic acid from the extract of Ligustrum lucidum can specifically inhibit the activity of γ-secretase, thereby rescuing the long-term potentiation and enhancing synaptic plasticity in APP/PS1 mice. Inhibiting γ-secretase activity which leads to the decline of inflammatory factors (such as IFN-γ, IL-8) not only directly improves the pathology of AD, but also reduces Aβ production. Melatonin reduces the transcriptional expression of GSK-3β mRNA, thereby decreasing the levels of GSK-3β and reducing the phosphorylation induced by GSK-3β. Hydrogen sulfide can inhibitGSK-3β activity via sulfhydration of the Cys218 site of GSK-3β, resulting in the suppression of Tau protein hyperphosphorylation, which ameliorate the motor deficits and cognitive impairment in mice with AD. This article reviews enzyme inhibitors and conformational optimization of enzyme inhibitors targeting the regulation of cholinesterase, monoamine oxidase, secretase, and GSK-3β. We are hoping to provide a comprehensive overview of drug development in the enzyme inhibitors, which may be useful in treating AD.

Correlation between the expression levels of miR-377-3p and miR-365-3p in serum and aqueous humor and the degree of diabetes macular edema / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To explore the correlation between the expression levels of microRNA-377-3p(miR-377-3p)and microRNA-365-3p(miR-365-3p)in serum and aqueous humor and the degree of diabetes macular edema(DME).METHODS: A total of 60 DME patients(60 eyes)admitted to 363 Hospital from February 2021 to February 2022 were selected in this prospective study(the severe eye was selected if both eyes had DME, while the right eye was selected if the same degree of DME), including 24 mild eyes, 21 moderate eyes and 15 severe eyes. In addition, another 60 patients(60 eyes)with type 2 diabetes(without fundus disease)admitted to our hospital during the same period were selected as the control group. The basic clinical data of all subjects were collected, including body mass index(BMI), smoking history, drinking history, hypertension, hyperlipidemia, the course of diabetes, glycated hemoglobin levels, fasting blood glucose and homocysteine(Hcy); the expression levels of miR-377-3p and miR-365-3p were detected by real-time fluorescent quantitative PCR(qRT-PCR).RESULTS: The course of diabetes, glycosylated hemoglobin, fasting blood glucose and Hcy in DME group were obviously higher than those in control group(all P&#x003C;0.05); the expression levels of miR-377-3p and miR-365-3p in serum of patients in DME group were lower than those in control group(all P&#x003C;0.05); the expression levels of miR-377-3p and miR-365-3p in serum and aqueous humor in severe group were obviously lower than those in moderate group and mild group, and those in moderate group were obviously lower than those in mild group(all P&#x003C;0.05); the expression levels of miR-377-3p and miR-365-3p in serum were negatively correlated with central macular thickness(CMT; r=-0.342, -0.374, all P&#x003C;0.05), the expression levels of miR-377-3p and miR-365-3p in aqueous humor were negatively correlated with CMT(r=-0.425, -0.503, all P&#x003C;0.05); the multivariate Logistic regression analysis showed that the course of diabetes, increased fasting blood glucose and Hcy were risk factors for DME in type 2 diabetes patients, and serum miR-377-3p and miR-365-3p were protective factors for DME in type 2 diabetes patients(P&#x003C;0.05).CONCLUSION: The expression of miR-377-3p and miR-365-3p in serum and aqueous humor of patients with DME is low, which is negatively related to the severity of DME patients.

Research progress of ProTide technology and its application in the development of antiviral drugs / 药学学报

ProTide technology is a kind of prodrug design strategy invented by the team of Christopher McGuigan. ProTides are aryloxyphosphoramidates (or aryloxyphosphonamidates) which contain a phosphorus atom combined with an amino acid ester and an aryloxy group. These prodrugs can efficiently cross the cell membrane and escape from the first rate-limiting step of phosphorylation, which afford effective solutions to the drawbacks of current nucleoside analogues. At present, ProTide technology has been extensively applied in the field of antiviral research. It has been successful in providing a number of approved drugs and clinical candidates, such as sofosbuvir and so much more, highlighting the promising future in drug discovery. This review summarizes the brief history and characteristics of ProTide technology, as well as its application in the exploration of antiviral drugs.

The PK bioanalysis method study of c-Met antibody-drug conjugate (RC108) in cynomolgus monkey / 药学学报

Antibody-drug conjugate (ADC) has the characteristics of low toxicity and high efficiency, and plays an important role in cancer treatment. However, due to the complexity of its structure, it brings difficulties in pharmacokinetic (PK) bioanalysis. This study established an analytical method for the detection of ADC (RC108) in cynomolgus monkey plasma by ligand-binding assay (LBA) and liquid chromatography tandem mass spectrometry (LC-MS/MS), which was used to analyze and quantify the total antibody, bound antibody and free drug in cynomolgus monkey plasma. Based on the LBA method, rabbit anti-RC108 Fab and mouse anti-MMAE (monomethyl auristatin E) mAb were pre-coated in 96-well plates as the total antibody and antibody binding reagents, respectively. The samples to be tested were added, and then the detection reagents were added in turn. Goat anti-human IgG (H+L)-HRP, chromogenic solution tetramethylbenzidine (TMB), H2SO4 terminate the reaction, read data at 450 nm/630 nm wavelength of microplate reader; LC-MS/MS analysis method quantifies MMAE concentration, and refer to relevant regulations for methodological validation. The analytical method for quantifying total antibody, bound antibody and free drug of RC108 drug obtained good accuracy and precision, and the selectivity, dilution linearity, hook effect, parallelism and stability were verified. Meet the requirements of biological analysis. Finally, a bioanalytical method for the determination of the concentration of the test substance RC108 (total antibody, conjugated antibody, free MMAE) in cynomolgus monkey plasma with high sensitivity and high throughput was established by LBA and LC-MS/MS method. Subsequent non-clinical research on PK research in cynomolgus monkeys will provide technical support.

Value of the nomogram based on HALP score in predicting the prognosis of patients with hepatocellular carcinoma after hepatectomy / 临床肝胆病杂志

Objective To investigate the value of HALP score in evaluating the prognosis of patients with hepatocellular carcinoma (HCC) after hepatectomy and whether the nomogram based on HALP score could effectively predict the postoperative survival of patients. Methods A retrospective study was performed for the clinical data of 253 HCC patients who underwent surgical treatment in Department of Hepatobiliary Surgery, The Affiliated Hospital of Southwest Medical University, from July 2013 to March 2020. The receiver operating characteristic (ROC) curve was plotted to calculate the optimal cut-off values of HALP score and other related indicators; the chi-square test was used to investigate the association between HALP score and clinicopathological features; the Kaplan-Meier method was used to plot survival curves, and the Log-rank test method was used for comparison. The univariate and multivariate Cox regression analyses were used to investigate the association of HALP score and other clinical parameters with the prognosis of patients. R3.6 was used to establish a nomogram; C-index and calibration curve were used to evaluate the predictive ability of the nomogram, and net reclassification index (NRI) and integrated discrimination improvement (IDI) were used to compare predictive ability between the nomogram model and the conventional model. Results The Kaplan-Meier analysis showed that the high HALP group had significantly better overall survival (OS) and recurrence-free survival (RFS) than the low HALP group ( P < 0.001). The univariate Cox regression analysis showed that white blood cell count, gamma-glutamyl transpeptidase (GGT), alkaline phosphatase (ALP), alpha-fetoprotein (AFP), surgical approach, microvascular invasion, TNM stage, degree of tumor differentiation, HALP, aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ratio, neutrophil-to-lymphocyte ratio (NLR), and monocyte-to-lymphocyte ratio (MLR) were significantly associated with OS (all P < 0.05). The variables with statistical significance in the univariate Cox regression analysis were included in the multivariate Cox regression analysis, and the results showed that ALP, AST/ALT ratio, ALP, AFP, degree of tumor differentiation, and TNM stage were independent influencing factors for OS after surgery in HCC patients (all P < 0.05). The univariate Cox regression analysis showed that GGT, ALP, AFP, microvascular invasion, TNM stage, degree of tumor differentiation, HALP, AST/ALT ratio, NLR, and MLR were significantly associated with RFS (all P < 0.05), and the multivariate Cox regression analysis showed that HALP, AST/ALT ratio, NLR, ALP, AFP, and TNM stage were independent influencing factors for RFS after surgery in HCC patients (all P < 0.05). The nomograms for OS and RFS of HCC patients were established based on the multivariate analysis. The nomogram for OS had a C-index of 0.732 (95% confidence interval [ CI ]: 0.691-0.774) and an area under the ROC curve of 0.795, 0.791, and 0.775, respectively, in predicting 1-, 3-, and 5-year survival rates, and the nomogram for RFS had a C-index of 0.677 (95% CI : 0.637-0.717) and an area under the ROC curve of 0.742, 0.733, and 0.716, respectively, in predicting 1-, 3-, and 5-year survival rates. The calibration curves of 1-, 3-, and 5-year OS were well fitted to those of 1-, 3-, and 5-year RFS. Conclusion A low level of HALP before surgery is a predictive factor for poor long-term prognosis in HCC patients undergoing surgical treatment, and the nomogram model based on HALP score is superior to the BCLC staging model and can better predict the prognosis of HCC.

Advances in the study on cytokines related to dental pulp regeneration / 口腔医学

@#With the development of molecular biology, biomaterials and tissue engineering, regenerative treatment of pulpal and periradicular diseases is facing new opportunities. At present, a large number of studies on dental pulp regeneration reveal that cytokines are essential for promoting migration, proliferation and osteogenic differentiation of dental pulp stem cells. In this paper, we review several kinds of cytokines related to dental pulp regeneration, and analyze their roles and regulatory mechanisms in dental pulp regeneration.

Screening of housekeeping genes in Gelsemium elegans and expression patterns of genes involved in its alkaloid biosynthesis / 生物工程学报

Gelsemium elegans is a traditional Chinese herb of medicinal importance, with indole terpene alkaloids as its main active components. To study the expression of the most suitable housekeeping reference genes in G. elegans, the root bark, stem segments, leaves and inflorescences of four different parts of G. elegans were used as materials in this study. The expression stability of 10 candidate housekeeping reference genes (18S, GAPDH, Actin, TUA, TUB, SAND, EF-1α, UBC, UBQ, and cdc25) was assessed through real-time fluorescence quantitative PCR, GeNorm, NormFinder, BestKeeper, ΔCT, and RefFinder. The results showed that EF-1α was stably expressed in all four parts of G. elegans and was the most suitable housekeeping gene. Based on the coexpression pattern of genome, full-length transcriptome and metabolome, the key candidate targets of 18 related genes (AS, AnPRT, PRAI, IGPS, TSA, TSB, TDC, GES, G8H, 8-HGO, IS, 7-DLS, 7-DLGT, 7-DLH, LAMT, SLS, STR, and SGD) involved in the Gelsemium alkaloid biosynthesis were obtained. The expression of 18 related enzyme genes were analyzed by qRT-PCR using the housekeeping gene EF-1α as a reference. The results showed that these genes' expression and gelsenicine content trends were correlated and were likely to be involved in the biosynthesis of the Gelsemium alkaloid, gelsenicine.