PI3Kγ and PI3Kδ have important regulatory roles in the immune system, and targeting these two subtypes helps to reshape the tumor microenvironment. PI3Kγ and PI3Kδ are potential targets for tumor immunotherapy. In this study, a series of new pyrazolopyrimidine derivatives were designed and synthesized on the basis of our previously reported PI3K inhibitors, resulting in the discovery of compound 16l as a potent and selective PI3Kγ/δ dual inhibitor. Compound 16l demonstrated strong biochemical potencies against PI3Kγ and PI3Kδ with IC₅₀ values of 0.11 and 0.79 nmol·L^-1. In cell-based assays, it potently inhibited the PI3Kγ and PI3Kδ mediated Akt S473 phosphorylation with EC₅₀ values of 3 and 7 nmol·L^-1. In vivo, compound 16l exhibited acceptable pharmacokinetic properties in Sprague-Dawley (SD) rats and suppressed the tumor growth in a MC38 syngeneic mouse model. The animal experiments were approved by the Animal Ethics Committee of Hefei Institutes of Physical Science, Chinese Academy of Sciences (approval number: DWLL-2000-06). In addition, no appreciable human ether-a-go-go-related gene (hERG) inhibition was observed for compound 16l even at 30 μmol·L^-1. These results suggested that compound 16l might be a potential research tool for studying the PI3Kγ/δ mediated signaling pathways.

Objective To evaluate the effectiveness of treatment for osteoarthritis of the first carpometacarpal joint.Methods From June 2019 to June 2022,15 patients with osteoarthritis of the first carpometacarpal joint underwent a combined procedure of trapezium excision,first carpometacarpal joint arthroplasty,ligament reconstruction,and tendon interposition.Surgical efficacy was assessed using X-rays,thumb joint range of motion,grip strength,pinch strength,and pain rating(VAS).Results 9 months postoperative follow-up revealed significant pain reduction,increased thumb range of motion,enhanced grip and pinch strength,with an overall surgical excellence rate of 86.7％.Conclusion Trapeziecotomy arthroplasty with ligament reconstruction and tendon tamponade demonstrates significant efficacy in treating osteoarthritis of the first carpometacarpal joint,effectively alleviating pain,improving thumb mobility,and enhancing hand strength.The method is simple and effective.

Objective To observe the change in the prevalence of post-traumatic stress disorder(PTSD)1 year after trauma exposure and analyze the risk factors of PTSD 1 year after trauma exposure.Methods Convenience sampling was conducted at the initial outbreak of the coronavirus disease 2019 epidemic and 1 year later,respectively.Participants participated in the anonymous online survey.The survey consisted of 2 self-completed questionnaires:1 collected personal information(gender,age,education level,occupation)and subjective sleep quality;the other is the PTSD checklist(PCL-5)from the Diagnostic and Statistical Manual of Mental Disorders,5th edition.Valid questionnaires of 2 091 and 2 092 were respectively retrieved at the initial stage of trauma exposure and 1 year later.Results The prevalence of PTSD at the initial stage of trauma exposure was 5.3％(111/2 091)and 1 year after trauma exposure was 19.1％(399/2 092).Multiple linear regression analysis showed that age(P＜0.01),gender(P＜0.01),and subjective sleep quality(P＜0.01)were risk factors related to PTSD.Conclusions One year after trauma exposure,the prevalence of PTSD increases.Psychological intervention measures should be given at the early stage of trauma exposure,and special attention should be paid to young individuals,women,and those with sleep disorders.

Objective To propose a method for classifying small bowel capsule endoscopy images by combining the Swin Transformer network with an improved Adapt-RandAugment data augmentation approach,aiming to enhance the accuracy and efficiency of small bowel lesion classification and recognition.Methods An Adapt-RandAugment data augmentation approach was formulated based on the RandAugment data enhancement sub-strategy and the principles of no feature loss and no distortion when enhancing small bowel capsule endoscopy images.In the publicly available Kvasir-Capsule dataset of small bowel capsule endoscopic images,the Adapt-RandAugment data augmentation approach was trained based on the Swin Transformer network,and the convolutional neural networks ResNet152 and DenseNet161 were used as the benchmarks to validate the combined Swin Transformer network and Adapt-RandAugment data augmentation approach for small bowel capsule endoscopy image classification.Results The proposed algorithm gained advantages over ResNet152 and DenseNet161 networks in the indicators,which had the macro average precision(MAC-PRE),macro average recall(MAC-REC),macro average F1 score(MAC-Fi-S)being 0.383 2,0.314 8 and 0.290 5 respectively,the micro average precision(MIC-PRE),micro average recall(MIC-REC)and micro average F1 score(MIC-Fi-S)all being 0.755 3,and the Matthews correlation coe-fficient(MCC)being 0.452 3.Conclusion The proposed small bowel capsule endoscopy image classification method based on Swin Transformer network and Adapt-RandAugment data augmentation approach behaves well in classified recognition efficiency and accuracy.[Chinese Medical Equipment Journal,2024,45(6):9-16]

Non-communicable diseases(NCDs),including cardiovascular diseases,cancer,metabolic diseases,and skeletal diseases,pose significant challenges to public health worldwide.The complex pathogenesis of these diseases is closely linked to oxidative stress and inflammatory damage.Nuclear factor erythroid 2-related factor 2(Nrf2),a critical transcription factor,plays an important role in regulating antioxidant and anti-inflammatory responses to protect the cells from oxidative damage and inflammation-mediated injury.Therefore,Nrf2-targeting therapies hold promise for preventing and treating NCDs.Quercetin(Que)is a widely available flavonoid that has significant antioxidant and anti-inflammatory properties.It modulates the Nrf2 signaling pathway to ameliorate oxidative stress and inflammation.Que modulates mitochondrial function,apoptosis,autophagy,and cell damage biomarkers to regulate oxidative stress and inflammation,highlighting its efficacy as a therapeutic agent against NCDs.Here,we discussed,for the first time,the close association between NCD pathogenesis and the Nrf2 signaling pathway,involved in neurodegenerative diseases(NDDs),cardiovascular disease,cancers,organ damage,and bone damage.Furthermore,we reviewed the availability,pharmacokinetics,pharmaceutics,and therapeutic applica-tions of Que in treating NCDs.In addition,we focused on the challenges and prospects for its clinical use.Que represents a promising candidate for the treatment of NCDs due to its Nrf2-targeting properties.

As a traditional Chinese herb and functional food, the fruits of Lycium barbarum has been widely used for thousands of years in China. L. barbarum polysaccharides(LBPs) are predominant active components, which have immunomodulatory, antioxidant, hypoglycemic, neuroprotective, anti-tumor, and prebiotic activities. The molecular weight, monosaccharide composition, glycosidic bond, branching degree, protein content, chemical modification, and spatial structure of LBPs are closely related to their biological activity. Based on the previous studies of this research team, this paper systematically combed and integrated the research progress of structure, function, and structure-activity relationship of LBPs. At the same time, some problems restricting the clarification of the structure-activity relationship of LBPs were considered and prospected, hoping to provide references for the high value utilization of LBPs and in-depth exploration of their health value.
Lycium/chemistry* ; Drugs, Chinese Herbal/chemistry* ; Structure-Activity Relationship ; Antioxidants/pharmacology* ; Antineoplastic Agents ; Polysaccharides/chemistry*

Objective: : Covered stenting is an optional strategy for traumatic carotid pseudoaneurysm, especially in malignant conditions of potential rupture, but the long-term outcomes are not clear. Our aim was to determine if covered stenting is an effective option for traumatic carotid pseudoaneurysm with promising long-term outcomes. Methods: : Self-expanding Viabahn and balloon-expandable Willis covered stents were separately implanted for extra- and intracranial traumatic carotid pseudoaneurysm. The covered stent was placed across the distal and proximal pseudoaneurysm leakage under roadmap guidance. Procedural success was defined as technical success (complete exclusion of the pseudoaneurysm and patency of the parent artery) without a primary end point (any stroke or death within 30 days after the procedure). Longterm outcomes were evaluated as ischemic stroke in the territory of the qualifying artery by clinical follow-up through outpatient or telephone consultation and as the exclusion of the pseudoaneurysm and patency of the parent artery by imaging follow-up through angiography. Results: : Five patients with traumatic carotid pseudoaneurysm who underwent covered stenting were enrolled. The procedural success rate was 100%. No ischemic stroke in the territory of the qualifying artery was recorded in any of the five patients during a mean clinical follow-up of 44±16 months. Complete exclusion of the pseudoaneurysm and patency of the parent artery were maintained in all five patients during a mean imaging follow-up of 39±16 months. Conclusion : Satisfactory procedural and long-term outcomes were obtained, suggesting that covered stenting is an effective option for traumatic carotid pseudoaneurysm.

Objective:To compare the effects of spinal orthosis and exercise training on psychological status and quality of life in patients with adolescent idiopathic scoliosis (AIS). Methods:From July, 2017 to Febrary, 2018, 55 AIS patients aged ten to 16 years were enrolled. According to the individual's choice, they were divided into exercise group (n = 25) and orthosis group (n = 30). The Cobb's angle, apex vertebral rotation (AVR), trunk shift (TS) and apex vertebral translocation (AVT) were measured before, three months and six months after intervention. They were also evaluated with Scoliosis Research Society Patient Questionnaire-22 (SRS-22) before and six months after intervention. Results:Six months after intervention, the scores of function/activity level, pain, self-image/appearance and treatment satisfaction were better in the exercise group than in the orthosis group (t > 2.137, P < 0.05). Three months and six months after intervention, the Cobb's angles reduced significantly in both groups (t > 4.461, P < 0.001); six months after intervention, the Cobb's angle was smaller in the orthosis group than in the exercise group (t = 2.548, P < 0.05). Three months and six months after intervention, TS, AVR and AVT improved in both groups (t > 2.338, P < 0.05); six months after intervention, they were better in the orthosis group than in the exercise group (t > 2.259, P < 0.05). Conclusion:Single exercise training is effective on AIS patients with Cobb's angle between 25° to 40°, especially for psychological status and the quality of life, however, it isn't as better as orthotics treatment for deformity correction.

Objective To evaluate the performance of the Sendai Guidelines,Fukuoka Guidelines and Pancreatic Cystic Lesions Management Guidelines (Chinese guidelines) in predicting malignant mucinous pancreatic cystic neoplasms (PCN).Methods A retrospective analysis of 196 patients,who received surgery and were pathologically identified as PCN or intraductal papillary mucinous neoplasms (IPMN),underwent surgical resection in Ruijin Hospital affiliated with Shanghai Jiao Tong University from January 2003 to April 2017 was performed.The differences on clinical and pathological parameters between malignant mucinous and benign mucinous PCN were compared.The accuracy,sensitivity,specificity,positive predictive value (PPV)and negative predictive value (NPV) of the indications for surgery in the Sendai,Fukuoka and Chinese Guidelines in predicting malignant mucinous PCN were calculated.Results Of 196 patients,39 patients (19.9％) were confirmed as malignant tumors and 157 patients (80.1％) were confirmed as benign tumors by pathology.There were significant differences on age,symptoms (abdominal pain,jaundice or pancreatitis),tumor solid composition,pancreatic duct diameter,tumor site,tumor diameter ＞3 cm,and serum CA199 level between malignant and benign patients (all P ＜0.05).But there were no significant differences on gender distribution,tumor diameter,mural nodules and the proportion of mucinous cystic neoplasm (MCN)and intra-ductal papillary mucinous neoplasm (IPMN).165 patients (84.2％) met the Sendai Guidelines,153 patients (78.1％) met the Chinese guideline,and only 61 patients (31.1％) met the Fukuoka Guidelines.All 39 patients with malignant tumors met the indications in Sendai Guidelines and Chinese guidelines,and only 35 patients had the indication for surgery in the Fukuoka Guidelines.The accuracy,sensitivity,specificity,PPV and NPV of the Fukuoka Guidelines for predicting the malignancy were 84.7％,89.7％,83.4％,57.4％ and 97.0％,compared to 35.7％,100％,19.8％,23.6％ and 100％ for the Sendai and 41.8％,100％,27.4％,25.5％ and 100％ for the Chinese guidelines,respectively.Conclusions The performance of the Chinese guideline is slightly better than the Sendai Guidelines,while both of them can lead to a larger number of patients undergoing unnecessary surgical resection.Though the rate of missed diagnosis could reach 10.3％,the Fukuoka Guidelines gets the highest accuracy.

Objective To investigate the association between single nucleotide polymorphisms ( SNPs) of FOXO1 gene and type 2 diabetic nephropathy(T2DN). Methods A total of 654 Chinese Han patients with type 2 diabetes mellitus (T2DM;394 without and 260 with T2DN) were enrolled. Six FOXO1 gene tags SNPs were selected using the Hapmap database. The genotypes of six SNPs in FOXO1 were determined by PCR-RFLP, and the clinical characteristics of the subjects were also evaluated. The interaction of SNPs with these clinical factors was analyzed by multiple factor reduction(MDR) method. Results After adjusting for age, gender, DM course, body mass index ( BMI ) , HbA1C , total cholesterol ( TC ) , triglycerides ( TG ) , high-density lipoprotein-cholesterol ( HDL-C ) , low-density lipoprotein-cholesterol ( LDL-C ) , hypertension history, DM family history, smoking, and drinking, FOXO1 rs17446614 variant genotype was significantly associated with an increased risk of T2DN, while rs17446593 variant genotype was associated with a decreased T2DN risk. In the stratified analysis of risk factors, the correlation between rs17446614 and T2DN was unrelated with patient' s gender, hypertension history, and blood TC level. Simultaneously, rs17446614 variant genotype significantly increased the risk of T2DN in people older than 60 years,BMI less than 24 kg/m2 , LDL-C less than or equal to 3. 5 mmol/L , or DM family history. rs2721068 variant genotype significantly decreased the risk of T2DN in people less than 60 years old or without DM family history. rs2951787 variant genotype significantly increased the risk of T2DN in people with DM duration longer than 10 years or with DM family history. A variant genotype rs17592236 significantly increased the risk of T2DN in male or TC higher than 5 mmol/L. A variant genotype rs17446593 significantly decreased the risk of T2DN in male or those DM duration longer than 10 years, or BMI≥24 kg/m2 . The interactions among rs17446614, DM duration, TC, and hypertension history were also observed. Conclusion The genetic variants rs17446614, rs2721068, rs2951787, rs17592236, and rs17446593 in FoxO1 may contribute to the risk of T2DN in T2DM patients.