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.

ObjectiveTo investigate the influence of histone deacetylase 3 (HDAC3) on the occurrence, development of psoriasis-like inflammation in mice, and the relative immune mechanisms. MethodsHealthy C57BL/6 mice aged 6-8 weeks were selected and randomly divided into 3 groups: control group (Control), psoriasis model group (IMQ), and HDAC3 inhibitor RGFP966-treated psoriasis model group (IMQ+RGFP966). One day prior to the experiment, the back hair of the mice was shaved. After a one-day stabilization period, the mice in Control group was treated with an equal amount of vaseline, while the mice in IMQ group was treated with imiquimod (62.5 mg/d) applied topically on the back to establish a psoriasis-like inflammation model. The mice in IMQ+RGFP966 group received intervention with a high dose of the HDAC3-selective inhibitor RGFP966 (30 mg/kg) based on the psoriasis-like model. All groups were treated continuously for 5 d, during which psoriasis-like inflammation symptoms (scaling, erythema, skin thickness), body weight, and mental status were observed and recorded, with photographs taken for documentation. After euthanasia, hematoxylin-eosin (HE) staining was used to assess the effect of RGFP966 on the skin tissue structure of the mice, and skin thickness was measured. The mRNA and protein expression levels of HDAC3 in skin tissues were detected using reverse transcription real-time quantitative polymerase chain reaction (RT-qPCR) and Western blot (WB), respectively. Flow cytometry was employed to analyze neutrophils in peripheral blood and lymph nodes, CD4⁺ T lymphocytes, CD8⁺ T lymphocytes in peripheral blood, and IL-17A secretion by peripheral blood CD4⁺ T lymphocytes. Additionally, spleen CD4⁺ T lymphocyte expression of HDAC3, CCR6, CCR8, and IL-17A secretion levels were analyzed. Immunohistochemistry was used to detect the localization and expression levels of HDAC3, IL-17A, and IL-10 in skin tissues. ResultsCompared with the Control group, the IMQ group exhibited significant psoriasis-like inflammation, characterized by erythema, scaling, and skin wrinkling. Compared with the IMQ group, RGFP966 exacerbated psoriasis-like inflammatory symptoms, leading to increased hyperkeratosis. The psoriasis area and severity index (PASI) skin symptom scores were higher in the IMQ group than those in the Control group, and the scores were further elevated in the IMQ+RGFP966 group compared to the IMQ group. Skin thickness measurements showed a trend of IMQ+RGFP966>IMQ>Control. The numbers of neutrophils in the blood and lymph nodes increased sequentially in the Control, IMQ, and IMQ+RGFP966 groups, with a similar trend observed for CD4⁺ and CD8⁺ T lymphocytes in the blood. In skin tissues, compared with the Control group, the mRNA and protein levels of HDAC3 decreased in the IMQ group, but RGFP966 did not further reduce these expressions. HDAC3 was primarily located in the nucleus. Compared with the Control group, the nuclear HDAC3 content decreased in the skin tissues of the IMQ group, and RGFP966 further reduced nuclear HDAC3. Compared with the Control and IMQ groups, RGFP966 treatment decreased HDAC3 expression in splenic CD4⁺ and CD8⁺ T cells. RGFP966 treatment increased the expression of CCR6 and CCR8 in splenic CD4⁺ T cells and enhanced IL-17A secretion by peripheral blood and splenic CD4⁺ T lymphocytes. Additionally, compared with the IMQ group, RGFP966 reduced IL-10 protein levels and upregulated IL-17A expression in skin tissues. ConclusionRGFP966 exacerbates psoriatic-like inflammatory responses by inhibiting HDAC3, increasing the secretion of the cytokine IL-17A, and upregulating the expression of chemokines CCR8 and CCR6.

Due to the high similarity with the lipid layer between human skin keratinocytes, functional cosmetics with layered liquid crystal structure prepared by liquid crystal emulsification technology encapsulating natural active substances have become a hot research topic in recent years. This type of functional cosmetic often has a fresh and natural skin feel, excellent skin barrier repair function and efficient moisturizing effect, etc., showing great potential in cosmetic application. However, the present research on the application of liquid crystal emulsification technology to functional cosmetics is still in the initial stage, and there are fewer relevant reports with reference values. Based on the mentioned above, this review provides a comprehensive summary of functional cosmetics with layered liquid crystal structures prepared by liquid crystal emulsification technology from the following aspects: the structure of human skin, the composition of lamellar liquid crystal, the advantages of liquid crystal emulsification technology containing natural active substances used in the field of functional cosmetics, the preparation process, main components, influencing factors during the preparation and the market functional cosmetics with lamellar liquid crystal structure. Finally, the prospect of the application of liquid crystal emulsification technology in functional cosmetics is presented, to provide useful references for those engaged in the research of liquid crystal emulsification technology-related functional cosmetics.

Objective To analyze the diagnostic quality of imported malaria in Hubei Province from 2019 to 2022, and to further improve the diagnostic level and consolidate the achievements in eliminating malaria. Methods The samples of reported malaria cases in Hubei were collected by the provincial reference laboratory (PRL) from 2019 to 2022. The microscopy and fluorescent PCR were performed to confirm the infection of plasmodium species of each case．The positive coincidence rate and species coincidence rate were analyzed and compared． Results A total of 257 imported malaria cases were reported in Hubei Province from 2019 to 2022. Among 229 malaria cases were confirmed, the overall coincidence for malaria diagnosis was 91.24% (229/251), and the overall coincidence rate for parasite species identification was 86.03% (197/229). The difference in species coincidence rate among different years was statistically significant (χ²=10.458, P<0.05). The coincidence rates of malaria diagnosis and parasite species identification in different cities (prefectures) of Hubei Province were 71.43% to 100.00% and 50.00% to 100.00%, respectively, with significant differences among different regions (χ²=29.283, P<0.05). The coincidence rates of malaria diagnosis and parasite species identification were 72.73% to 100.00% and 0.00% to 100.00% in different diagnostic institutions, and the coincidence rate of species identification in hospitals (87.61%) was higher than that in Centers for Disease Control institutions (54.55%) (χ²=81.275, P<0.05). The coincidence rates of Plasmodium falciparum, P. vivax, P. malariae, and P. ovale identification were 91.50%, 88.57%, 80.00%, and 58.06%, respectively (χ²=19.777, P<0.05). Conclusion The quality of the qualitative diagnosis of malaria cases reported online from 2019 to 2022 is generally high. However, the ability of Plasmodium typing needs to be improved. In the future, technical training and quality control should be strengthened to improve the malaria surveillance capability during the post-elimination stage.

A novel series of 2-aryl substituted benzothiopyranone compounds was designed and synthesized based on our previously obtained benzothiopyranone scaffold with significant antituberculosis activity. All target compounds were evaluated for their antimycobacterial activity and preliminary druggability was subsequently investigated for some selected compounds with good activity. The results indicated that most compounds showed good activity against Mycobacterium tuberculosis H₃₇Rv. Among them, compounds 8g, 8h, 8q and 9f showed potent activity with MIC ranged from 0.2 to 0.4 μg·mL^-1. Furthermore, some active compounds exhibited low cytotoxicity and cardiotoxicity risk. It is worth noting that compounds 8h and 8q with good liver microsome stability and low inhibition of CYPs 3A4/5 and 2C9 were suitable for combination drug regimen to treat tuberculosis.

Objective To explore characteristics of clinical parameters and cytokines in patients with drug-induced liver injury(DILI)caused by different drugs and their correlation with clinical indicators. Method The study was conducted on patients who were up to Review of Uncertainties in Confidence Assessment for Medical Tests(RUCAM)scoring criteria and clinically diagnosed with DILI.Based on Chinese herbal medicine,cardiovascular drugs,non-steroidal anti-inflammatory drugs(NSAIDs),anti-infective drugs,and other drugs,patients were divided into five groups.Cytokines were measured by Luminex technology.Baseline characteristics of clinical biochemical indicators and cytokines in DILI patients and their correlation were analyzed. Results 73 patients were enrolled.Age among five groups was statistically different(P=0.032).Alanine aminotransferase(ALT)(P=0.033)and aspartate aminotransferase(AST)(P=0.007)in NSAIDs group were higher than those in chinese herbal medicine group.Interleukin-6(IL-6)and tumor necrosis factor alpha(TNF-α)in patients with Chinese herbal medicine(IL-6:P<0.001;TNF-α:P<0.001)and cardiovascular medicine(IL-6:P=0.020;TNF-α:P=0.001)were lower than those in NSAIDs group.There was a positive correlation between ALT(r=0.697,P=0.025),AST(r=0.721,P=0.019),and IL-6 in NSAIDs group. Conclusion Older age may be more prone to DILI.Patients with NSAIDs have more severe liver damage in early stages of DILI,TNF-α and IL-6 may partake the inflammatory process of DILI.

Objective To explore clinical effect of modified Chinese-way technique under shoulder arthroscopy in treating massive rotator cuff tears.Methods From January 2019 to June 2022,22 patients with massive rotator cuff tears who underwent arthroscopic rotator cuff repair with improved Chinese-way technique,including 10 males and 12 females,aged from 46 to 76 years old with an average of(64.14±7.45)years old;the courses of disease ranged from 5 to 14 months with an average of(8.32±2.42)months;19 patients were complete repaired,and 3 patients were partial repaired.Visual analogue scale(VAS)and University of California at Los Angeles(UCLA)scale were used to evaluate pain and function of shoulder joint preopera-tively and 1 year postoperatively.Postoperative complications,the integrity of reconstructed tissue structure and the size of sub-acromial space were observed.Results All patients were followed up from 12 to 34 months with an average of(17.14±5.93)months.Re-tear were occurred in 4 patients during MRI follow-up,but clinical symptoms of patients were improved significant-ly and they were satisfied with the treatment,the others were no complications such as incision infection,peripheral nerve in-jury,loosening and falling off of internal fixation anchors.Preoperative and 1 year after operation VAS were(8.05±1.12)and(1.82±1.50),UCLA scores were(7.45±1.65)and(31.41±2.87)respectively,and the difference was statistically significant(P＜0.05).Conclusion The modified Chinese-way technique under shoulder arthroscopy for the massive rotator cuff tear could relieve pain obviously and recovery postoperative function well,with satisfactory curative effect.

Objective:To explore the differential impact of the alignment between service capability and job satisfaction on job performance among primary general practitioner,and to provide a reference for enhancing their job performance.Methods:A survey was conducted with 620 primary general practitioner using questionnaires.The relationships among service capability,job satisfaction,and job performance were analyzed using polynomial regression and response surface analysis methods.Results:Under the condition of"service capability—job satisfaction alignment,"compared to the scenario of"low service capability—low job satisfaction,"primary general practitioner with"high service capability—high job satisfaction"demonstrated significantly higher job performance(a1=0.875,P＜0.001;a2=-0.068,P＞0.05).In the misalignment condition,compared to"low service capability—high job satisfaction,"those with"high service capability—low job satisfaction"also showed higher job performance(a3=0.265,P＜0.001;a4=-0.064,P＞0.05).Conclusion:Both service capability and job satisfaction significantly influence job performance among primary general practitioner,with service capability being a key factor for achieving high work performance.It is essential to enhance the service capability of primary general practitioner and adopt multiple strategies to improve job satisfaction,thereby effectively boosting work performance.

Blood transfusion accuracy is crucial for disease treatment and emergency rescue. Prior to a blood transfusion, it is essential to perform a number of tests to assure proper clinical treatment and reduce the risk of complications. Pre-transfusion testing refers primarily to the blood group, coagulation, and infection to assure transfusion safety and prevent cross-infection. Blood type, cross-matching blood, fibrinogen, viral hepatitis, human immunodeficiency virus, and syphilis are routine pre-transfusion tests. Immunoassay is the traditional clinical pretransfusion detection method. With the expansion of clinical treatment requirements from hospital to on-site treatment, new technologies, such as electrochemical sensing, microfluidics, and spectroscopy technology, are being developed gradually for rapid detection prior to blood transfusion. The development of technologies including colloidal gold immunity and biochips has facilitated the shift from large-scale laboratory equipment to portable testing for pre-transfusion screening. Further, the introduction of artificial intelligence technologies such as machine learning, biometric technology, and computer vision has contributed to the advancement of intelligent pre-transfusion testing. This article reviews the various application scenarios, benefits, and drawbacks of different pre-transfusion detection technologies, analyzes the application of a series of new technologies in pre-transfusion detection and its future development trend, and provides a reference for promoting the development of pre-transfusion detection and even rapid disease marker detection.

Objective To investigate disease characteristics and hospitalization costs of children with Mycoplasma Pneumoniae pneumonia(MPP)admitted to Shanghai municipal medical hospitals from 2019 to 2023.Methods Depending on the Shanghai Municipal Hospital Pediatric Alliance,we retrospectively investigated community acquired MPP pediatric patients hospitalized in 22 municipal hospitals with pediatric qualifications(including 4 children's hospitals)in Shanghai from Jan 2019 to Dec 2023.We collected the patients'diagnosis codes,gender,age,length of hospital stay,hospitalization costs,and whether they progressed to severe Mycoplasma pneumoniae pneumonia(SMPP).Results From 2019 to 2023,a total of 29 045 hospitalized children with MPP were treated,with 6 035 cases(20.8%)identified as SMPP in the 22 hospitals.Trend analysis revealed a rising trend with years in the proportion of SMPP patients(χ2trend=365.498,P<0.001).Among the 4 children's hospitals,there were 18 710 cases with MPP,including 4 078 cases(21.8%)of SMPP.The proportion of SMPP patients also showed an increasing trend with years(χ2trend=14.548,P<0.001),and the proportion in 2023(23.0%)was higher than that in previous years with statistical significance.There were statistical differences in the seasonal distribution of MPP cases between different years,with higher proportions in summer and autumn overall.The age distribution of hospitalized MPP children varied among different years,with school-age children accounting for the majority(56.8%)in 2023.There was no difference in the distribution of severe cases between different genders,but there were differences in the proportion of severe cases among different age groups in different years,with a gradual increase in severe cases among children aged 1 to 3 years(χ2trend=191.567,P<0.001).The average length of hospital stay for MPP during the epidemic was higher than that during non-epidemic periods,and there were statistically significant differences in the average length of hospital stay between different years(P<0.001).The individual hospitalization costs during the epidemic were higher than in other years,and there were statistically significant differences in individual hospitalization costs between different years(P<0.001).The total hospitalization costs were still higher in 2019 and 2023.The individual hospitalization costs for SMPP were higher than for non-SMPP cases.Conclusion MPP outbreaks occurred in Shanghai in 2019 and 2023,with the higher proportions in summer and autumn overall.Compared to previous years,the number of hospitalized MPP children in Shanghai was higher in 2023,with a higher proportion of SMPP cases,especially among children under 3 years old.The individual per capita hospitalization expenses for SMPP cases were higher than for non-SMPP cases.