19 cinnamamide/ester-triazole compounds were designed, synthesized and evaluated for their anti-Alzheimer's disease (AD) activity. Among them, compound 4f displayed excellent anti-β-amyloid protein (Aβ)-mediated cytotoxicity (EC₅₀ = 2.03 ± 2.45 μmol·L^-1) in APPswe cells and acetylcholinesterase inhibiton (IC₅₀ = 4.88 ± 4.70 μmol·L^-1). Further study indicated that, at dosages of (1, 5 and 25 mg·kg^-1), compound 4f was effective in improving spatial learning and memory deficits in Aβ_1-42-impaired mice, which was achieved by promoting the nonamyloidogenic signaling and inhibiting the amyloidogenic pathway, along with the suppression of Aβ-induced Tau phosphorylation. All animal experiments in this study were approved by the Experimental Animal Care and Use Committee of the Institute of Medicinal Biotechnology (IMB-20220908D701). In conclusion, compound 4f holds promise as a lead candidate for AD treatment, and the present study lays the foundation for its subsequent development.

Objective:To explore the expression levels of serum triple domain 35 (TRIM35) and tumor necrosis factor receptor associated factor 3 (TRAF3) in patients with acute pancreatitis (AP) and their correlation with the severity and prognosis of the disease.Methods:Using a prospective research method, 93 patients with AP (observation group) were selected from July 2020 to September 2022 in Qinghai Red Cross Hospital, including 40 cases of mild acute pancreatitis (MAP), 29 cases of moderate to severe acute pancreatitis (MSAP) and 24 cases of severe acute pancreatitis (SAP). During the same period, 40 healthy individuals who underwent physical examinations were selected as healthy control group. The serum TRIM35 and TRAF3 levels were detected by real time fluorescence quantitative polymerase chain reaction (RT-qPCR). The survival status after 28 d of admission was followed up. The correlation was analyzed by Pearson method. Multivariate Logistic regression analysis was used to analyze the relationship between serum TRIM35 and TRAF3 levels and the prognosis in patients with AP. The efficacy of serum TRIM35 and TRAF3 in predicting the prognosis in patients with AP was evaluated by the receiver operating characteristics (ROC) curve.Results:The serum TRIM35 and TRAF3 levels in observation group were significantly higher than those in healthy control group (3.76 ± 1.36 vs. 1.02 ± 0.19 and 5.37 ± 2.18 vs. 1.04 ± 0.16), and there were statistical differences ( P<0.01). The serum TRIM35 and TRAF3 levels in patients with MSAP and SAP were significantly higher than those in patients with MAP (4.11 ± 1.73 and 4.96 ± 1.47 vs. 2.79 ± 1.04, 5.43 ± 2.15 and 7.01 ± 2.85 vs. 4.35 ± 1.79), the indexes in patients with SAP were significantly higher than those in patients with MSAP, and there were statistical differences ( P<0.05). The follow-up results showed that 11 cases died and 82 cases survived. The serum TRIM35 and TRAF3 levels in death patients were significantly higher than those in surviving patients (4.94 ± 1.01 vs. 3.60 ± 1.67 and 7.08 ± 1.43 vs. 5.14 ± 2.57), and there were statistical differences ( P<0.05). Pearson correlation analysis result showed that serum TRIM35 level was positive correlation with serum TRAF3 level in patients with AP ( r = 0.483, P<0.01). Multivariate Logistic regression analysis result showed that serum TRIM35 and TRAF3 levels were the independent risk factors of prognosis in patients with AP ( OR = 1.86 and 1.37, 95% CI 1.12 to 3.09 and 1.02 to 1.82, P<0.05). ROC curve analysis result showed that the area under the curve of serum TRIM35 combined with TRAF3 levels for evaluating the prognosis in patients with AP was significantly larger than serum TRIM35 and TRAF3 alone (0.85 vs. 0.81 and 0.81, Z = 0.03 and 0.04, P<0.05). The optimal cutoff values of serum TRIM35 and TRAF3 levels were 4.90 and 6.11. Conclusions:The serum TRIM35 and TRAF3 levels in patients with AP are significantly elevated, and are related to the severity of the condition. The serum TRIM35 and TRAF3 levels are independent risk of prognosis in patients with AP, and their combined detection is more valuable in evaluating the prognosis in patients with AP.

【Objective】 To investigate the protective effects of aflexible sleeve penile protection device on reducing postoperative pain and wound edema in patients after circumcision. 【Methods】 A total of 54 patients who underwent circumcision at Yan’an Branch of Peking University Third Hospital during Feb.1 and May 31, 2023 were enrolled.The patients were randomly divided into the experimental group and control group, with 27 patients in either groups.Patients in the experimental group were treated with a flexible sleeve penis protection device after surgery, and patients in the control group were treated with traditional gauze bandage after surgery.Postoperative pain, wound edema and complications were compared between the two groups. 【Results】 In terms of pain, the visual analogue scale of the experimental group was significantly lower at 6 hours [(1.7±0.9) vs.(3.3±1.9), P<0.001] and 2 days [(2.0±1.3) vs.(3.3±1.3), P<0.001] after surgery than that of the control group, but there were no statistically significant differences between the two groups on the 4th and 7th postoperative days (P>0.05).In terms of edema, the edema score of the experimental group was significantly lower than that of the control group on the 2nd postoperative day [(2.0±1.0) vs.(4.0±0.8), P<0.001] , the 4th postoperative day [(1.5±1.2) vs.(2.6±0.9), P<0.001] , and the 7th postoperative day [(0.9±1.3) vs.(2.3±1.5), P<0.001] .There was no statistically significant difference in the incidence of complications between the two groups (P>0.05). 【Conclusion】 The flexible sleeve penile protection device has significant effects of reducing early postoperative pain and reducing edema in patients undergoing circumcision.

Objective To investigate the mechanism of the interaction between Wnt/β-catenin signaling and the epithelial mesenchymal transition(EMT)pathway in mediating sunitinib-resistance in renal cancer cells.Methods The sunitinib-resistant kidney cancer cell lines were constructed by stepwise increase in drug concentrations method with sunitinib,and were divided into resistance group,lv-NC group and lv-Twist group,and human kidney cancer cell lines were selected as normal group.The normal and drug-resistant groups were treated with conventional culture;the lv-NC group was treated with 40 μL of lv-NC lentivirus supernatant containing 2.25 × 108 TU·mL-1 for 72 h,and the lv-Twist group was treated with 50 μL of Twist lentivirus supernatant containing 1.64 × 108 TU·mL-1 for 72 h.The apoptosis ability was detected by flow cytometry;the cell migration ability was detected by cell scratch assay;the cell invasion ability was detected by Transwell assay;and the protein expression levels of Wnt1,β-catenin and Twist were detected by Western blotting assay.Results The apoptosis rates of control,resistant,lv-NC and lv-Twist groups were(17.60±0.59)％,(8.61±0.34)％,(8.60±0.40)％and(3.10±0.34)％;the migration rates were(14.10±0.12)％,(27.64±0.41)％,(14.24±0.45)％and(32.74±2.53)％;the number of invading cells was 27.33±1.15,53.33±1.53,46.00±2.65 and 99.33±2.52;the relative expression levels of Wnt1 protein were 0.10±0.01,0.96±0.06,0.39±0.03 and 3.09±0.31;the relative expression levels of β-catenin protein were 0.39±0.01,1.48±0.16,0.81±0.05 and 1.24±0.14;the relative expression levels of Twist protein were 0.10±0.02,0.91±0.04,0.39±0.03 and 3.09±0.31,respectively.The differences of above indexes were statistically significant between the resistant group and the normal group,and between the lv-Twist group and the lv-NC group(all P＜0.05).Conclusion Twist(EMT related protein)mediates sunitinib resistance in renal cell carcinoma by interacting with Wnt/β-catenin signaling pathway.

Objective To make an epidemiological investigation on traditional Chinese medicine(TCM)dampness syndrome manifestations in the population at risk of cerebrovascular diseases in Guangdong area.Methods A cross-sectional study was conducted to analyze the clinical data related to the risk of cerebrovascular diseases in 330 Guangdong permanent residents.The diagnosis of dampness syndrome,quantitative scoring of dampness syndrome and rating of the risk of stroke were performed for the investigation of the distribution pattern of dampness syndrome and its influencing factors.Results(1)A total of 306(92.73%)study subjects were diagnosed as dampness syndrome.The percentage of dampness syndrome in the risk group was 93.82%(258/275),which was slightly higher than that of the healthy group(48/55,87.27%),but the difference was not statistically significant(χ2 = 2.91,P = 0.112).The quantitative score of dampness syndrome in the risk group was higher than that of the healthy group,and the difference was statistically significance(Z =-2.24,P = 0.025).(2)Among the study subjects at risk of cerebrovascular disease,evaluation time(χ2 = 26.11,P = 0.001),stroke risk grading(χ2= 8.85,P = 0.031),and history of stroke or transient ischemic attack(TIA)(χ2 = 9.28,P = 0.015)were the factors influencing the grading of dampness syndrome in the population at risk of cerebrovascular disease.Conclusion Dampness syndrome is the common TCM syndrome in the population of Guangdong area.The manifestations of dampness syndrome are more obvious in the population with risk factors of cerebrovascular disease,especially in the population at high risk of stroke,and in the population with a history of stroke or TIA.The assessment and intervention of dampness syndrome should be taken into account for future project of stroke prevention in Guangdong.

Amorphous solid dispersion (ASD) is one of the most effective formulation approaches to enhance the water solubility and oral bioavailability of poorly water-soluble drugs. However, maintenance of physical stability of amorphous drug is one of the main challenges in the development of ASD. Crystallization is a process of nucleation and crystal growth. The nucleation is the key factor that influences the physical stability of the ASD. However, a theoretical framework to describe the way to inhibit the nucleation of amorphous drug is not yet available. We reviewed the methods and theories of nucleation for amorphous drug. Meanwhile, we also summarized the research progress on the mechanism of additives influence on nucleation and environmental factors on nucleation. This review aims to enhance the better understanding mechanism of nucleation of amorphous drug and controlling over the crystal nucleation during the ASD formulation development.

Objective:To study the expressions of bronchoalveolar lavage fluid(BALF), C-reactive protein (C reactive protein, CRP), procalcitonin (PCT) and Interleukin 6 (IL-6) in mechanically ventilated patients with chronic obstructive pulmonary diseases (COPD) and their clinical significance.Methods:A total of 128 COPD patients with mechanical ventilation admitted to the Third People's Hospital of Chengdu from September 2022 to September 2023 were selected as the study subjects. They were divided into VAP group and non-VAP group according to the occurrence of ventilator associated pneumonia (VAP). Comparison of general data between the two groups, measurement data in line with normal distribution were expressed xˉ± s, and independent sample t test was used to compare the mean between groups. Enumeration data were expressed as constituent ratio, and χ2 test was used to compare between groups. Multivariate Cox regression was used to analyze the influencing factors of VAP in COPD patients. The diagnostic value of CRP, procalcitonin and IL-6 in BALF and serum for VAP was evaluated by receiver operating characteristic (ROC) curve. Results:There were 32 cases of VAP and 96 cases of non-VAP in 128 COPD patients with mechanical ventilation. In the VAP group, the duration of mechanical ventilation was (5.12±0.48) days, and 13 patients (40.63%) had used antibiotics within 3 months, while in the non-VAP group, the duration of mechanical ventilation was (4.79±0.69) days, and 56 patients (61.46%) had used antibiotics within 3 months, respectively. There were significant differences between the two groups ( t=2.51, χ2=4.23, all P<0.05). The levels of CRP, procalcitonin and IL-6 in BALF of VAP group were (26.46±6.78) mg/L, (2.47±0.69) ng/L and (751.46±126.44), and in the non-VAP group, they were (20.47±6.26) mg/L, (1.12±0.32) ng/L and (447.89±68.69) μg/L, respectively. There were significant differences between the two groups ( t=4.59, 15.00, 17.18, all P<0.001). The serum levels of CRP, procalcitonin and IL-6 in VAP group were (124.78±26.32) mg/L, (10.53±2.20) ng/L and (221.69±45.46). The non-VAP group was (96.78±24.96) mg/L, (6.46±1.89) ng/L and (146.36±42.34) μg/L, respectively ( t=5.42, 10.12, 8.56; all P<0.001). Multivariate Cox regression analysis showed that mechanical ventilation time, BALF and serum CRP, procalcitonin and IL-6 were independent factors affecting the occurrence of VAP in COPD patients ( OR values were 1.578, 1.687, 1.669, 1.844,1.645, 1.775 and 1.659, respectively). 95% CI were 1.017-2.447, 1.066-2.669, 1.076-2.588, 1.148-2.963, 1.086-2.493, 1.172-2.690 and 1.084-2.538, all P<0.05). ROC curve showed that the AUC of CRP, procalcitonin and IL-6 in BALF and serum were 0.758/0.792, 0.965/0.930 and 0.977/0.900 respectively ( P values were 0.049/0.046, 0.030/0.030 and 0.021/0.033, respectively). Conclusion:The expressions of CRP, procalcitonin and IL-6 in BALF and serum of COPD patients with mechanical ventilation have high clinical diagnostic value, which can assist the diagnosis of early VAP.

Objective To investigate the characteristics of gut flora related to dampness syndrome in the population at risk of cerebrovascular disease and to explore their influencing factors.Methods Based on the results of epidemiological investigation of damp syndrome in at-risk population of cerebrovascular disease in Guangdong from October 2021 to February 2023,60 subjects(including 41 at-risk cases of cerebrovascular disease and 19 healthy controls)were included in the study.The identification of dampness syndrome and the risk rating of stroke were carried out for the subjects,and fecal samples were collected.High-throughput 16S rRNA sequencing technology and bioinformatics methods were used to analyze the characteristics of gut flora.Results(1)A total of 53 cases(88.33％)were identified as dampness syndrome.There was significant difference in the quantitative score of dampness syndrome between the risk group and the healthy group,and between the low-,medium-and high-risk groups(P=0.016;P=0.041).(2)There was no statistical difference in the species and abundance of gut flora between the dampness syndrome group and the non-dampness syndrome group.(3)In the population identified as dampness syndrome,there was no significant difference in Alpha diversity between the healthy group and the risk group,but there was significant difference in Beta diversity analysis;LEfSe analysis found that Fusobacterium and Lactobacillus were enriched in the risk group;correlation analysis showed that the differential bacteria were related to the three risk factors of diabetes,dyslipidemia and obesity and carotid intima-media thickness(IMT).(4)In the population identified as dampness syndrome and having the risk of cerebrovascular disease,there was no significant difference in Alpha diversity among three groups with different levels of risks,while significant difference in Beta diversity was observed;LEfSe analysis showed that Acidaminococcaceae,Phascolarctobacterium and Butyricimonas were enriched in the low-risk group,Veillonellaceae was enriched in the medium-risk group,and Ruminococcus 2 and Alloprevotella were enriched in the high-risk group;correlation analysis showed that the differential bacteria were associated with high-density lipoprotein cholesterol(HDL-C),low-density lipoprotein cholesterol(LDL-C),white blood cell count(WBC),and neutrophil count(NEUT).Conclusion In the Guangdong population predominated by dampness syndrome,the severity of dampness syndrome is related to the risk of stroke,and the specific flora associated with sub-clinical atherosclerosis,inflammatory response and lipid metabolism are presented.

Pharmacokinetics of traditional Chinese medicine(TCM)is a discipline that adopts pharmacokinetic research methods and techniques under the guidance of TCM theories to elucidate the dynamic changes in the absorption,distribution,metabolism and excretion of active ingredients,active sites,single-flavour Chinese medicinal and compounded formulas of TCM in vivo.However,the sources and components of TCM are complex,and the pharmacodynamic substances and mechanisms of action of the majority of TCM are not yet clear,so the pharmacokinetic study of TCM is later than that of chemical medicines,and is far more complex than that of chemical medicines,and its development also confronts with challenges.The pharmacokinetic study of TCM originated in the 1950s and has experienced more than 70 years of development from the initial in vivo study of a single active ingredient,to the pharmacokinetic and pharmacodynamic study of active ingredients,to the pharmacokinetic study of compound and multi-component of Chinese medicine.In recent years,with the help of advanced extraction,separation and analysis technologies,gene-editing animals and cell models,multi-omics technologies,protein purification and structure analysis technologies,and artificial intelligence,etc.,the pharmacokinetics of TCM has been substantially applied in revealing and elucidating the pharmacodynamic substances and mechanisms of action of Chinese medicines,research and development of new drugs of TCM,scientific and technological upgrading of large varieties of Chinese patent medicines,as well as guiding the rational use of medicines in clinics.Pharmacokinetic studies of TCM have made remarkable breakthroughs and significant development in theory,methodology,technology and application.In this paper,the history of the development of pharmacokinetics of TCM and the progress of cutting-edge research was reviewed,with the aim of providing ideas and references for the pharmacokinetics of TCM and related research.

Background::Dual-energy computed tomography (DECT) is purported to accurately distinguish uric acid stones from non-uric acid stones. However, whether DECT can accurately discriminate ammonium urate stones from uric acid stones remains unknown. Therefore, we aimed to explore whether they can be accurately identified by DECT and to develop a radiomics model to assist in distinguishing them.Methods::This research included two steps. For the first purpose to evaluate the accuracy of DECT in the diagnosis of uric acid stones, 178 urolithiasis patients who underwent preoperative DECT between September 2016 and December 2019 were enrolled. For model construction, 93, 40, and 109 eligible urolithiasis patients treated between February 2013 and October 2022 were assigned to the training, internal validation, and external validation sets, respectively. Radiomics features were extracted from non-contrast CT images, and the least absolute shrinkage and selection operator (LASSO) algorithm was used to develop a radiomics signature. Then, a radiomics model incorporating the radiomics signature and clinical predictors was constructed. The performance of the model (discrimination, calibration, and clinical usefulness) was evaluated.Results::When patients with ammonium urate stones were included in the analysis, the accuracy of DECT in the diagnosis of uric acid stones was significantly decreased. Sixty-two percent of ammonium urate stones were mistakenly diagnosed as uric acid stones by DECT. A radiomics model incorporating the radiomics signature, urine pH value, and urine white blood cell count was constructed. The model achieved good calibration and discrimination {area under the receiver operating characteristic curve (AUC; 95% confidence interval [CI]), 0.944 (0.899–0.989)}, which was internally and externally validated with AUCs of 0.895 (95% CI, 0.796–0.995) and 0.870 (95% CI, 0.769–0.972), respectively. Decision curve analysis revealed the clinical usefulness of the model.Conclusions::DECT cannot accurately differentiate ammonium urate stones from uric acid stones. Our proposed radiomics model can serve as a complementary diagnostic tool for distinguishing them in vivo.