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 investigate the screening results and factors affecting abnormal detection rates among high-risk groups of esophageal cancer and to explore effective intervention measures. Methods We investigated and collected the information on gender, education level, age, marital status, symptoms of reflux esophagitis (heartburn, acid reflux, belching, hiccup, foreign body sensation in the pharynx, and difficulty swallowing), consumption of pickled vegetables, salt use, and esophageal cancer incidence of villagers in a natural village in Wenfeng District, Anyang City, Henan Province. Changes in reflux esophagitis symptoms in the high-incidence area of esophageal cancer before and after 16 years were observed, and the relationship of such changes with esophageal cancer was analyzed. Results In 2008, 711 cases were epidemiologically investigated, including 213 cases with one of the symptoms of reflux esophagitis such as heartburn, acid reflux, belching, hiccups, foreign body sensation in the pharynx, and difficulty swallowing (sorted in accordance with the abovementioned symptoms; if there are multiple symptoms, then the former is taken); 55 cases with at least two related symptoms, among which the most symptom was heartburn in 108 cases (15.1%); followed by acid reflux, belching, etc. In 2024, the same group of people was investigated, and eight people were missing because of relocation. A total of 703 people were successfully investigated, of which 189 cases (26.8%) had one of the symptoms of reflux esophagitis, such as heartburn (sorted in accordance with relevant symptoms, if there are multiple symptoms, then the former will be selected); 167 cases (23.7%) had at least two related symptoms, among which the most symptom was heartburn in 139 cases (19.7%); followed by acid reflux. Over 16 years, among the 703 people investigated, 45 cases had esophageal cancer and they had one or more of the abovementioned symptoms. No significant differences in the reflux esophagitis-like symptoms were found between 2008 and 2024 (P=0.26); no significant differences in the composition of reflux esophagitis-like symptoms were found between 2008 and 2024 (P=0.299). Conclusion The detection rate of reflux esophagitis-related symptoms in the population in a high-risk area of esophageal cancer has not decreased in the past 16 years, and the high-risk factors still exist. Esophageal cancer is closely related to reflux esophagitis, and clinical practice can provide early diagnosis and treatment for high-risk population.

Objective To understand the disease spectrum of a natural village in an area with high incidence of esophageal cancer to provide a reference for precise prevention and control. Methods From 2008 to 2024, 711 asymptomatic people over the age of 35 years in a natural village with high incidence of esophageal cancer in China were surveyed, and 171 of them were subjected to gastroscopy, biopsy, and pathological examination. All participants were followed up for a long time, and their disease history was recorded. Results A total of 16 years of follow-up were performed, and 703 people were effectively followed up. In 2008, 171 people underwent gastroscopy, and 160 people had biopsy and pathological results in endoscopic screening. By 2024, 76 people had been diagnosed with malignant tumors of 12 different types, and among these people, 45 had esophageal cancer. Conclusion Esophageal cancer remains a significant cause of morbidity and mortality from malignant tumors in this region. Biopsy and pathological examination should be strengthened during gastroscopy, and follow-ups and regular check-ups should be given high importance to reduce the incidence and mortality rates of esophageal cancer.

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 explore the relationship between the expressions of P21,P27 and proliferating cell nuclear antigen(PCNA)in glomerular mesangial tissue and poor renal prognosis in patients with immunoglobulin A(IgA)nephropathy.Methods:A total of 145 patients with IgA nephropathy treated in Xiaogan Central Hospital from April 2017 to August 2019 were selected as the research object.The expressions of P21,P27 and PCNA in glomerular mesangial tissue were detected by immunohistochemistry.All patients were followed up for 24 months,and the prognosis were counted.The expressions of P21,P27 and PCNA in glomerular mesangial tissue of patients with different prognosis were compared and the influencing factors of poor prognosis in patients with IgA nephropathy were analyzed by Logistic regression analysis.Results:The expression rates of P21,P27 and PCNA positive cells in glomerular mesangial tissue of patients with IgA nephropathy were(38.69±6.83)%,(55.94±8.08)%,(33.47±5.72)%,respectively.The incidence rete of poor prognosis in patients with IgA nephropathy was 17.24%,and the expression rates of P21 and PCNA positive cells in glomerular mesangial tissue of patients with poor prognosis were higher than those in good prognosis group(P<0.05),while the expression rate of P27 positive cells was lower than that in good prognosis group(P<0.05).Logistic multiple regression analysis showed that elevated diastolic blood pressure,increased 24 h proteinuria,mesangial cell proliferation,segmental glomerulosclerosis,renal tubular atrophy/interstitial fibrosis,crescentic body,increased expression rates of P21 and PCNA positive cells and decreased expression rate of P27 positive cells were all risk factors affecting the poor prognosis of patients with IgA nephropathy(P<0.05).Conclusion:There are positive expressions of P21,P27 and PCNA in glomerular mesangial tissue of IgA nephropathy.The expression rates of P21 and PCNA positive cells in glomerular mesangial tissue of of patients with poor prognosis of IgA nephropathy are higher than those with good prognosis,while the expression rate of P27 protein positive cells is lower than those with good prognosis,which are risk factors for poor prognosis of patients with IgA nephropathy.

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 investigate the effect and influencing factors of non-invasive correction of infants with congenital auricular deformity.Methods:The data of infants with congenital auricular deformity were retrospectively analyzed, who were treated with domestic external ear orthosis in the Department of Otolaryngology Head and Neck Surgery of Tianjin Hospital from January 1, 2019 to June 30, 2023. Before treatment, the skin was prepared routinely. First, the orthosis base was installed and pressed to fit the skin around the ear. Then, according to the type of auricle deformity, the ear hook and ear cover were installed, and the adhesive tape was fixed. During the corrective treatment, the orthosis was worn all day, and the treatment was ended if there was no obvious rebound after 1 month of observation. The complications were closely observed during treatment. After the treatment, the treatment effect was evaluated and divided into markedly effective, effective and ineffective. The markedly effective rate (markedly effective ears/total ears × 100%) and effective rate [(markedly effective ears + effective ears)/ total ears × 100%] were calculated. At the same time, the cure time of the markedly effective children was recorded, and they were grouped according to different types of auricle deformities and the initial age of correction (<2, 2-6, >6 weeks groups), and the related indicators were compared. SPSS 23.0 software was used for statistical analysis. The measurement data were expressed by Mean±SD. The comparison between multiple groups was analyzed by one-way ANOVA. The pairwise comparison between groups was performed by LSD method. The counting data was expressed by frequency (% or ratio). The comparison between multiple groups was performed by χ 2 test, and the pairwise comparison between groups was performed by Fisher test with adjusted α value. Results:A total of 31 cases (55 ears) were included, including 13 males (23 ears) and 18 females (32 ears), aged 4 to 127 d. There were 13 lop ears, 6 constricted ears, 6 cup ears, 4 Stahl’s ears, 5 prominent ears, 18 helical rim deformity ears, 2 conchal crus ears and 1 Ⅱ degree microtia ear. During the treatment, 5 ears had skin lesions, 5 ears had mild allergic reactions, and 2 ears had severe allergic reactions, who improved significantly and continued treatment after removal of the external orthosis and use of erythromycin ointment. After noninvasive correction treatment, the auricle deformity of the children was improved to different extent. The overall markedly effective rate was 70.91% (39/55), and the overall effective rate was 90.91% (50/55). The markedly effective rate of lop ear, constricted ear, cup ear, Stahl’s ear, prominent ear, helical rim deformity ear, conchal ear and Ⅱ degree microtia ear were 13/13, 4/6, 4/6, 4/4, 4/5, 8/18, 2/2, 0/1 respectively. The average cure time of 39 markedly effective ears was (36.08±14.77) d. The cure time of different auricle deformity types was statistically significant ( P<0.01). Pairwise comparison between the groups showed that the cure time of lop ears was shorter than constricted ears, cup ears, Stahl’s ear, prominent ears, and that the cure time of prominent ears was longer than lop ears, constricted ears, cup ears, Stahl’s ears, helical rim deformity ears, conchal crus ears (all P<0.05). According to different initial ages of correction, the children were divided into <2-week-old group (12 cases, 21 ears), 2-6-week-old group (10 cases, 18 ears), and >6-week-old group (9 cases, 15 ears), excluding 1 Ⅱ degree microtia ear. The markedly effective rates were (90.5%) 19/21, 13/18, and 7/15, respectively, with statistically significant differences ( P<0.05). The comparison between groups showed that the markedly effective rate of <2-week-old group was significantly higher than that of >6-week-old group ( P<0.017), but there was no statistically significant difference in the cure time among the three groups ( P>0.05). Conclusion:The effect of non-invasive correction for congenital auricular deformity in infants is significant. The type of congenital auricular deformity is a key factor that affects the therapeutic effect and cure time. In lop ear, Stahl’s ear, prominent ear and conchal crus deformity, good therapeutic effects can be seen, but in constricted ear, cup ear, helical rim deformity ear and Ⅱ degree microtia, the effects are poor. The cure time of lop ear is short, while the cure time of prominent ear is long. The better effect can be acquired in the earlier non-invasive correction.

Objective To monitor the susceptibility of clinical isolates to antimicrobial agents in tertiary hospitals in major regions of China in 2022.Methods Clinical isolates from 58 hospitals in China were tested for antimicrobial susceptibility using a unified protocol based on disc diffusion method or automated testing systems.Results were interpreted using the 2022 Clinical &Laboratory Standards Institute(CLSI)breakpoints.Results A total of 318 013 clinical isolates were collected from January 1,2022 to December 31,2022,of which 29.5％were gram-positive and 70.5％were gram-negative.The prevalence of methicillin-resistant strains in Staphylococcus aureus,Staphylococcus epidermidis and other coagulase-negative Staphylococcus species(excluding Staphylococcus pseudintermedius and Staphylococcus schleiferi)was 28.3％,76.7％and 77.9％,respectively.Overall,94.0％of MRSA strains were susceptible to trimethoprim-sulfamethoxazole and 90.8％of MRSE strains were susceptible to rifampicin.No vancomycin-resistant strains were found.Enterococcus faecalis showed significantly lower resistance rates to most antimicrobial agents tested than Enterococcus faecium.A few vancomycin-resistant strains were identified in both E.faecalis and E.faecium.The prevalence of penicillin-susceptible Streptococcus pneumoniae was 94.2％in the isolates from children and 95.7％in the isolates from adults.The resistance rate to carbapenems was lower than 13.1％in most Enterobacterales species except for Klebsiella,21.7％-23.1％of which were resistant to carbapenems.Most Enterobacterales isolates were highly susceptible to tigecycline,colistin and polymyxin B,with resistance rates ranging from 0.1％to 13.3％.The prevalence of meropenem-resistant strains decreased from 23.5％in 2019 to 18.0％in 2022 in Pseudomonas aeruginosa,and decreased from 79.0％in 2019 to 72.5％in 2022 in Acinetobacter baumannii.Conclusions The resistance of clinical isolates to the commonly used antimicrobial agents is still increasing in tertiary hospitals.However,the prevalence of important carbapenem-resistant organisms such as carbapenem-resistant K.pneumoniae,P.aeruginosa,and A.baumannii showed a downward trend in recent years.This finding suggests that the strategy of combining antimicrobial resistance surveillance with multidisciplinary concerted action works well in curbing the spread of resistant bacteria.

To investigate the existence of tick-borne pathogens infection of rodents at the border of China and the Demo-cratic People's Republic of Korea(DPRK).PCR was used to detect the spotted fever group rickettsiae(SFGR)ompA gene,Ehrlichia chaffeensis(Ec)and Anaplasma phagocytophilum(Ap)16S rRNA,Candidatus Neoehrlichia mikurensis(CNm)groEL gene,Bartonella(Ba)rpoB gene,and Francisella tularensis(Ft)fopA gene in rodents samples collected from Ji'an of Jilin province and Kuandian of Liaoning Province.The positivity rates of 132 wild rats spleen samples,SFGR,Ec,Ap,CNm,Ba,and Ft were 9.85％,12.88％,5.30％,3.79％,51.52％,and 6.06％,respectively,with statistical differences in in-fection rates(x2=149.236,P=0.000).The infection rate of Ba was the highest in wild rats in this area.There was no signifi-cant difference in the infection rate of SFGR,Ec,Ap,CNm,and Ft among different rats species,but there were significant differences in the infection rate of Ba(x2=13.36,P=0.010).The infection rate of Apodemus agrarius was the highest.A-mong 132 wild rats specimens,the coinfection rate of the two pathogens was 15.9％(21/132),with Ba as the main species(15/132),and two cases of coinfection with three pathogens were detected.The infection of six tick-borne pathogens is common in wild rats at the China/DPRK border.Co-infection of two or three pathogens indicates a risk of multiple tick-borne pathogens and mixed natural foci of multiple tick-borne infec-tious diseases.

Objective:To investigate the anti-chronic myelogenous leukemia(CML)activity of Nur77-specific agonist Csn-B combined with imatinib by promoting Nur77 expression,and explore the potential role of its signaling pathway.Methods:Firstly,CCK-8 and Transwell assay were used to detect the inhibitory effects of Csn-B,imatinib,and their combination on the proliferation and migration of K562 cells.Furthermore,the apoptosis rate of K562 cells treated with Csn-B,imatinib,and their combination was detected by flow cytometry.The expression levels of Nur77,Pim-1,Drp1,p-Drp1 S616,Bcl-2 and Bax in K562 cells were detected by Western blot.Finally,the expression levels of reactive oxygen species(ROS)in K562 cells treated with Csn-B,imatinib and their combination were detected by immunofluorescence assay.Results:The level of Nur77 in CML patients decreased significantly compared with normal population in dataset of GSE43754(P＜0.001).Csn-B combined with imatinib could significantly inhibit the proliferation and migration of K562 cells(both P＜0.001),and induce apoptosis(P＜0.001).Csn-B promoted Nur77 expression in K562 cells,and synergistically enhanced imatinib sensitivity when combined with imatinib.Csn-B combined with imatinib could significantly enhanced ROS levels in K562 cells and mitochondria compared with single-drug treatment(both P＜0.001).Conclusion:Csn-B combined with imatinib can enhance ROS expression and induce apoptosis of K562 cells through Nur77/Pim-1/Drp1 pathway.