1.Biosensor analysis technology and its research progress in drug development of Alzheimer's disease
Shu-qi SHEN ; Jia-hao FANG ; Hui WANG ; Liang CHAO ; Piao-xue YOU ; Zhan-ying HONG
Acta Pharmaceutica Sinica 2024;59(3):554-564
		                        		
		                        			
		                        			 Biosensor analysis technology is a kind of technology with high specificity that can convert biological reactions into optical and electrical signals. In the development of drugs for Alzheimer's disease (AD), according to different disease hypotheses and targets, this technology plays an important role in confirming targets and screening active compounds. This paper briefly describes the pathogenesis of AD and the current situation of therapeutic drugs, introduces three biosensor analysis techniques commonly used in the discovery of AD drugs, such as surface plasmon resonance (SPR), biolayer interferometry (BLI) and fluorescence analysis technology, explains its basic principle and application progress, and summarizes their advantages and limitations respectively. 
		                        		
		                        		
		                        		
		                        	
2.Myricetin attenuates renal fibrosis by activating Nrf2/HO-1 pathway to inhibit oxidative stress
Dong-xue LI ; Zhou HUANG ; Han-yu WANG ; Zhi-hao ZHANG ; Ning-hua TAN ; Xue-yang DENG
Acta Pharmaceutica Sinica 2024;59(2):359-367
		                        		
		                        			
		                        			 This paper investigates the effect of myricetin (MYR) on renal fibrosis induced by unilateral ureteral obstruction (UUO) and common bile duct ligation (CBDL) in mice and its mechanism. The animal experiment has been approved by the Ethics Committee of China Pharmaceutical University (NO: 2022-10-020). Thirty-five ICR mice were divided into control, UUO, UUO+MYR, CBDL and CBDL+MYR groups. H&E and Masson staining were used to detect pathological changes in kidney tissues. Western blot (WB) was used to detect the expression of fibrosis-related proteins in renal tissue, and total superoxide dismutase (SOD) activity detection kit (WST-8) was used to detect the changes of total SOD in renal tissue of CBDL mice. 
		                        		
		                        	
3.Possible mechanisms of multi-pathway biological effects of laser therapy for knee osteoarthritis
Xinqi LOU ; Hao ZHONG ; Xiyu WANG ; Haoyu FENG ; Pengcui LI ; Xiaochun WEI ; Yanqin WANG ; Xiaogang WU ; Weiyi CHEN ; Yanru XUE
Chinese Journal of Tissue Engineering Research 2024;28(34):5521-5527
		                        		
		                        			
		                        			BACKGROUND:Laser therapy is a non-invasive and painless treatment that is considered to be an effective method suitable for the treatment of osteoarthritis due to its simplicity and non-invasive nature.Currently,the mechanism of action of laser therapy is unclear and the results of studies on its clinical application are controversial. OBJECTIVE:To review and summarize the latest research progress of laser therapy on chondrocytes,animal experiments and clinical efficacy,and to explore the possible mechanism of laser-mediated multi-pathway biological effects,so as to provide a theoretical basis for further research on the laser treatment of osteoarthritis of the knee joint. METHODS:A literature search was performed in CNKI,WanFang Data,VIP and PubMed databases for relevant literature published from 2018 to 2023,with"laser therapy,low level laser therapy,high level laser therapy,photobiomodulation,knee osteoarthritis,chondrocytes"as the search terms in Chinese and English,respectively.Together with 14 articles searched manually,70 articles were finally included for review. RESULTS AND CONCLUSION:Laser therapy in the treatment of knee osteoarthritis is mainly categorized into two types:low-level laser therapy and high-level laser therapy.Differences in laser parameters and treatment protocols have a direct impact on laser efficacy.When appropriate parameters are used,low-level lasers show positive effects in cellular experiments,animal models,and clinical efficacy.High-level lasers have been less studied in the treatment of knee osteoarthritis,but some preliminary clinical studies have shown positive results.Cell experiments have shown that low-level laser promotes chondrocyte proliferation and cartilage matrix synthesis,thereby reducing inflammatory response.Animal experiments have shown that low-level laser can reduce the release of pro-inflammatory factors,promote cartilage matrix synthesis,inhibit matrix degradation,and effectively improve the repair process of cartilage tissue.Low-level laser is also able to reduce oxidative stress damage and relieve pain in knee osteoarthritis.In clinical trials,both low-and high-level laser can reduce patients'pain and improve functional activities.The combination of laser therapy and exercise therapy modalities may improve the therapeutic effect.Lasers may affect intracellular signaling and cellular functions through photobiological or thermodynamic effects.This provides direct evidence that laser promotes articular cartilage regeneration.
		                        		
		                        		
		                        		
		                        	
4.Fetal facial ultrasound plane recognition based on real-time object detection network and its application
Zhonghua LIU ; Weifeng YU ; Xiuming WU ; Hao XUE ; Guorong LÜ ; Xiaoli WANG ; Peizhong LIU
Chinese Journal of Medical Physics 2024;41(2):247-252
		                        		
		                        			
		                        			Objective To explore the role of an artificial intelligence(AI)model based on real-time object detection network in fetal facial ultrasound examination.Methods With the normal fetal facial ultrasound standard plane(FFUSP)at 20-24 weeks of gestation as the research object,a FFUSP recognition model based on real-time object detection network was constructed.The recognition accuracy of the model for FFUSP and the anatomical structures were analyzed,and the clinical value was evaluated by analyzing its performance in identifying FFUSP in 119 cases of fetal ultrasound images.Results The overall precision,recall rate,mAP@.5 and mAP@.5:.95 of the AI model were 97.8%,98.5%,98.1%and 61.0%,respectively.The clinical validation showed that the AI model had a sensitivity,specificity,positive predictive value,negative predictive value and accuracy of 100.0%,98.5%,87.4%,100.0%and 98.7%for facial anatomy recognition,and the results were highly consistent with the classification of fetal ultrasound experts(k=0.925,P<0.001).The recognition accuracy of the model for 3 types of standard planes reached 100%;and the average speed of dynamic video detection was 33.93 frames per second.Conclusion The FFUSP recognition model based on real-time object detection network exhibits excellent performance,and it can be applied to real-time ultrasound diagnosis,teaching and intelligent quality evaluation.
		                        		
		                        		
		                        		
		                        	
5.Study on the potentiation effect of Puerariae Lobatue Radix and Acori Tatarinowii Rhizoma on PNS in the improvement of blood-brain barrier damage in MCAO rats based on the opening and closing of sweat pores
Linyao HAO ; Shuangyang LI ; Junhao REN ; Xiaoqiang WANG ; Lingxue WANG ; Dechou ZHANG ; Hongmei TANG ; Xue BAI
International Journal of Traditional Chinese Medicine 2024;46(8):1006-1014
		                        		
		                        			
		                        			Objective:To observe the neuroprotective effect of wind medicine (Puerariae Lobatue Radix and Acori Tatarinowii Rhizoma) in combination with Panax ginseng total saponin (PNS) on cerebral ischemia-reperfusion rats; To elucidate the mechanism of "wind medicine increasing effect".Methods:Totally 140 male SD rats were divided into sham-operation group, model group, PNS group, Puerariae Lobatue Radix group, Acori Tatarinowii Rhizoma group, Puerariae Lobatue Radix + PNS group, Acori Tatarinowii Rhizoma + PNS group according to the random number table method, with 20 rats in each group. Except for the sham-operation group, the cerebral ischemia/reperfusion rat model was established using the modified Longa line bolus method in the remaining groups. After 7 d of administration of the appropriate pharmacologic intervention in each group, neurological dysfunction was evaluated by Zea-longa score after final administration, cerebral infarct volume was determined by TTC staining; blood brain barrier (BBB) permeability of brain tissue on the ischemic side was detected by Evans blue content; BBB ultrastructure of each group of rats was observed by transmission electron microscopy; Claudin 5 protein expression level was detected by immunohistochemistry; Zonula occludens-1 (ZO-1), major facilitator supeffamily domain-containing protein 2a (Mfsd2a), Occludin, P-glycoprotein (P-gp), Monocarboxylate Transporters-1 (MCT1) and breast cancer resistance protein (BCRP) protein expression levels were detected by Western-blot.Results:Compared with the model group, the rat neurological function scores were reduced in each administration group ( P<0.05), infarct volume was reduced ( P<0.05), EB content of brain tissue decreased ( P<0.05), protein expressions of Claudin 5, ZO-1, Mfsd2a and Occludin in brain tissue were elevated ( P<0.05), the protein expressions of P-gp, BCRP and MCT1 were reduced ( P<0.05), and the protein expressions of Claudin 5, Mfsd2a, and Occludin was higher in the Puerariae Lobatue Radix + PNS group and Acori Tatarinowii Rhizoma + PNS group than that of each group of medication alone ( P<0.05), and the protein expression of MCT1 was lower than that of each group of medication alone ( P<0.05); the protein expression level of ZO-1 in the Puerariae Lobatue Radix + PNS group was higher than that of the group of medication alone ( P<0.05); P-gp protein expression was lower in Acori Tatarinowii Rhizoma + PNS group than in the PNS group and Acori Tatarinowii Rhizoma group ( P<0.05). Conclusion:Wind medicine (Puerariae Lobatue Radix and Acori Tatarinowii Rhizoma) may potentiate the neuroprotective effect of PNS on cerebral ischemia-reperfusion rats, and the mechanism may be related to the protection of BBB structural integrity and maintenance of central barrier properties, while regulating substance transport proteins and increasing the intracerebral content of the drug.
		                        		
		                        		
		                        		
		                        	
6.Key Information Textual Research and Quality Marker Prediction Analysis of the Ancient Classic Formula Huangqin Decoc-tion
Jiahao WANG ; Limei GU ; Hao XUE ; Yu LI ; Yu CHEN ; Ziyan LENG ; Renshou CHEN
Journal of Nanjing University of Traditional Chinese Medicine 2024;40(11):1263-1274
		                        		
		                        			
		                        			Huangqin Decoction is a classic formula published in the Catalogue of Ancient Classical Famous Prescriptions(the Sec-ond Batch).This paper systematically collates,researches and analyzes the ancient and modern clinical literature that records Huan-gqin Decoction,sorts out key issues such as the prescription origin,composition,medicine origin,processing method,usage and dos-age,efficacy and indications of Huangqin Decoction,and performs predictive analysis on its quality markers(Q-Marker)to provide lit-erature and theoretical support for the clinical application and preparation development of Huangqin Decoction from the entire process of textual research-preparation development-quality evaluation.After analysis and research,it is found that Huangqin Decoction is de-rived from Zhang Zhongjing's Treatise on Cold Damage.It consists of Scutellaria baicalensis,Radix Paeoniae Alba,and Glycyrrhiza,with Jujube serving as the guiding herb.The medicine origin follows the 2020 edition of the Chinese Pharmacopoeia.Scutellaria ba-icalensis and Radix Paeoniae Alba are taken in the raw form;Glycyrrhiza is lightly fried and Jujubes with sliced pieces.The doasge of medicine is 11.19 of Scutellaria baicalensis,7.46 g of Radix Paeoniae Alba and Glycyrrhiza,and jujubes are added or subtracted ac-cording to the situation.The method of preparation and administration is that all herbs are added with 2 000 mL of water,decocting to 600 mL.The decoction can be consumed warm 3 times a day at any suitable time.The formula was commonly used in ancient times for dysentery,but now it is also used for other digestive system diseases such as ulcerative colitis and chronic colitis,which are mainly characterized by diarrhea.The suggested Q-markers for Huangqin Decoction are baicalin,baicalein,wogonin,paeoniflorin,glycyrrhi-zin and glycyrrhizic acid.
		                        		
		                        		
		                        		
		                        	
7.Contralateral endoscopic approach for lumbar foraminal stenosis using unilateral biportal endoscopic surgery
Wei CHENG ; Rong-Xue SHAO ; Cheng-Yue ZHU ; Dong WANG ; Wei ZHANG ; Hao PAN
China Journal of Orthopaedics and Traumatology 2024;37(4):331-337
		                        		
		                        			
		                        			Objective To assess the feasibility and imaging outcomes of unilateral biportal endoscopic technique in the treatment of lumbar foraminal stenosis through contralateral approach.Methods The clinical data of 33 patients with lumbar foraminal stenosis treated with unilateral biportal endoscopic technique from January 2021 to July 2022 were retrospectively analyzed.There were 17 males and 16 females;age ranging from 34 to 72 years old with an average of(56.00±7.89)years old;operation time and perioperative complications were recorded;visual analogue scale(VAS)of pain was recorded,to evaluate the degree of low back pain and lower extremity pain,and Oswestry disability index(ODI)to evaluate the lumbar spine func-tion.At the latest follow-up,the modified Macnab score was used to evaluate the clinical efficacy.Results All patients success-fully completed the operation.The operation time ranged from 47 to 65 minutes,with an average of(56.10±5.19)minutes.The postoperative follow-up ranged from 12 to 18 months,with an average of(14.9±2.3)months.The VAS of low back and lower extermity pain before operation were(7.273±1.442)and(7.697±1.447)scores,ODI was(69.182±9.740)%.Postoperative lumbocrural pain VAS were(3.394±0.966)and(2.818±0.727)scores,ODI was(17.30±4.78)%.At the latest follow-up,VAS of back and lower extermity pain was(2.788±0.650)and(2.394±0.704)scores,ODI was(14.33±350)%.There were signifi-cant differences in VAS of low back and lower extremity pain and ODI before and after operation(P<0.05).At the latest follow-up,according to the modified Macnab criteria,24 patients got excellent result,5 as good,2 as fair,and 2 as poor.Conclusion Unilateral biportal endoscopic treatment of lumbar foraminal stenosis through the contralateral approach is a safe and efficient method,with few complications,quick postoperative recovery,and satisfactory clinical outcomes.During the follow-up period,no iatrogenic lumbar instability was observed.
		                        		
		                        		
		                        		
		                        	
8.Bladder large cell lymphoma: a case report and literature review
Hao WANG ; Butang LI ; Chenfei CHI ; Xincheng JIANG ; Weijing YE ; Qi CHEN ; Guoliang YANG ; Wei XUE
Journal of Modern Urology 2024;29(2):122-125
		                        		
		                        			
		                        			【Objective】 To improve the understanding and diagnosis and treatment level of ALK negative anaplastic large cell lymphoma (ALK-ALCL) by sharing the diagnosis and treatment process of a patient with ALK-ALCL treated in Hangzhou Bay Hospital of Ningbo. 【Methods】 The clinical data and diagnosis and treatment process of the patient were retrospectively analyzed, and relevant literature was reviewed. 【Results】 The patient was a young male, with recurrent gross hematuria and right low back pain as the initial symptoms.Imaging examination indicated bladder tumor.After resection, the tumor was reduced and confirmed to be ALK-ALCL.After chemotherapy and autologous hematopoietic stem cell transplantation, the patient’s condition continued to improve.During the follow-up, no recurrence was observed. 【Conclusion】 Primary ALK-ALCL in the bladder is very rare and prone to misdiagnosis and missed diagnosis in clinical practice.The successful diagnosis and treatment experience of this patient can provide clinical reference.
		                        		
		                        		
		                        		
		                        	
9.Visual Analysis of Current Status and Hotspots of Research on Ancient Classical Formulas Based on CiteSpace
Yu LI ; Jiahao WANG ; Hao XUE ; Luning WANG ; Renshou CHEN
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(22):20-26
		                        		
		                        			
		                        			ObjectiveTo analyze the current research status of the classical formulas in China and predict the future development trends, thus providing reference and suggestions for the scientific research and clinical application of classical formulas. MethodThe relevant publications were retrieved from China National Knowledge Infrastructure (CNKI) with the time interval from January 1, 2008 to August 1, 2023, and the publications were counted. CiteSpace 6.1.R6 was used for visual analysis of the authors, research institutions, and keywords. ResultA total of 847 valid publications were included in this study. The annual number of publications showed a rapid rise after 2018. The Chinese Journal of Experimental Traditional Medical Formulae was the main journal publishing the articles about ancient classical formulas in China. ZHAN Zhilai, BAI Jie, LU Tulin, FU Chaomei, and CHEN Renshou were active researchers in this field and had formed stable research teams. The China Academy of Chinese Medical Sciences and its affiliated institutions published the most articles and had close cooperation with other research institutions in China. The co-occurrence network and cluster map of keywords showed that textual research on materia medica, clinical application, quality standard, fingerprint, and mechanism of action were the core keywords. The top 3 bursts in this field were benchmark samples, quality evaluation, and origin. ConclusionThe current research on ancient classical formulas still has shortcomings such as lack of large-scale cooperation between teams and weak transformation of research achievements. At present, the research hotspots in this field mainly include textural research on key information, quality control and fingerprinting, and clinical application. The future research in this field mainly focus on benchmark samples of classical formula preparations, quality evaluation of medicinal materials, pharmacodynamic material basis, and mechanisms of classical formulas. 
		                        		
		                        		
		                        		
		                        	
10.Effects of Buzhong Yulin Decoction (补中愈淋汤) for Mice with Recurrent Urinary Tract Infectionon on Bladder Mucosal Barrier and Bacterial Load of Bladder Epithelial Cells
Hao YIN ; Yi XUE ; Biao ZHANG ; Zhuohui JIN ; Jiaoli ZHU ; Yi JIANG ; Xiaofang WANG ; Chen FENG ; Yunyun JIN ; Qingjiang JIN ; Qinglei JIN ; Xin WANG
Journal of Traditional Chinese Medicine 2024;65(22):2338-2346
		                        		
		                        			
		                        			ObjectiveTo investigate the possible mechanism of Buzhong Yulin Decoction (补中愈淋汤) in the prevention and treatment of recurrent urinary tract infection. MethodsThe mouse models of recurrent urinary tract infection were established by uropathogenic Escherichia coli (UPEC) strain UTI89 by bladder perfusion, and the successful mouse models were randomly divided into a model group, an antibiotic group, and a low- and high-dose Buzhong Yulin Decoction group, with six mice in each group. In addition, 5 C57BL/6 mice without modelling were taken as blank group. The low- and high-dose Buzhong Yulin Decoction groups received 0.1 ml/10 g of decoction by gavage, with concentrations of 1.3 g/ml and 5.2 g/ml, respectively; the antibiotic group received 0.1 ml/10 g of levofloxacin hydrochloride solution with 5 mg/ml by gavage; the blank and model groups received 0.1 ml/10 g of distilled water by gavage. Each group was gavaged once a day for 7 consecutive days. The total number of urine marks, the number of central urine marks, and the total urine volume of the urine marks were observed by the urine marking test; HE staining was used to observe the histopathological changes in the bladder of mice; serum levels of the inflammatory factors interleukin 1β (IL-1β), interleukin 6 (IL-6) and tumour necrosis factor α (TNF-α) were detected by ELISA; the morphology of the epithelial cells of bladder was observed by scanning electron microscopy; immunofluorescence assay to detect bladder tissue anti-UroPlakin 3A protein level and UPEC bacterial load; the spread plate method to detect urinary bacterial load and bacterial load of bladder epithelial cells; RT-PCR method to detect Ras-related protein Rab-11A (RAB11A) and Ras-related protein Rab-27B (RAB27B) mRNA level in bladder tissue; immunoblotting to detect microtubule-associated protein 1 light chain3 (LC3) and P62 protein levels in bladder tissue. ResultsCompared with the blank group, the bladder epithelial cell layers were lost and showed abnormal morphology in mice of the model group; bladder tissue UroPlakin 3A protein and RAB11A and RAB27B mRNA levels reduced, the total number of urine marks, the number of central urine marks, bladder tissue UPEC bacterial load, urinary bacterial load, bacterial load in bladder epithelial cells, serum IL-1β, IL-6, and TNF-α levels, and LC3 and P62 protein levels in bladder tissue all elevated (P<0.05 or P<0.01). Compared with the model group, the bladder epithelial cell layers were intact and the morphology of epithelial cells were regular in the low- and high-dose Buzhong Yulin Decoction groups; the average surface area of bladder epithelial cells reduced, the levels of UroPlakin 3A protein and RAB11A and RAB27B mRNA in bladder tissues elevated, and total number of urine marks, the number of central urine marks, bladder tissue UPEC bacterial load, urinary bacterial load, bacterial load in bladder epithelial cells, serum IL-1β, IL-6, and TNF-α levels, and P62 protein levels in bladder tissue all reduced (P<0.05 or P<0.01), but LC3 protein levels showed no statistically significant (P>0.05). In the antibiotic group, the bladder epithelial cells were partially missing and the morphology of epithelial cells was abnormal. Compared with the antibiotic group, the average surface area of the bladder epithelial cells in the mice increased in the low- and high-dose Buzhong Yulin Decoction groups, the bacterial load of the bladder epithelial cells decreased, and the P62 protein level of the bladder tissue decreased (P<0.05). When comparing between the low- and high-dose Buzhong Yulin Decoction groups, the differences in each index were not statistically significant (P>0.05). ConclusionBuzhong Yulin Decoction may prevent and treat recurrent urinary tract infection by repairing the bladder mucosal barrier, increasing RAB11A and RAB27B level and enhancing autophagy in bladder tissues, thereby facilitating bacterial clearance from bladder epithelial cells and reducing the bacterial load of bladder epithelial cells. 
		                        		
		                        		
		                        		
		                        	
            
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