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 observe the clinical efficacy of Chinese materia medica soaking therapy combined with cervical rotation-traction manipulation in the treatment of cervical spondylotic radiculopathy (CSR).Methods:A randomized controlled trial was conducted. Totally 84 CSR patients from the Orthopedics Department of Shunyi Hospital, Beijing Traditional Chinese Medicine Hospital from April 2023 to May 2024 were selected as the observation subjects. They were divided into two groups using a random number table method, with 42 patients in each group. The treatment for both groups lasted for 14 d. VAS scale was used to assess pain levels before and after treatment, OASTCSR was used to evaluate cervical function, and NDI was used to assess cervical functional status; adverse reactions during treatment were observed and recorded, and clinical efficacy was evaluated.Results:The total effective rate was 95.24% (40/42) in the treatment group and 80.95% (34/42) in the control group, with statistical significance ( χ2=4.36, P=0.029). After treatment, the VAS score (1.60±1.21 vs. 2.91±1.12, t=-1.89), the OASTCSR score (5.17±2.14 vs. 9.31±3.82, t=-11.57), and the NDI score (9.17±2.13 vs. 13.36±3.45, t=-10.82) in the treatment group were lower than those in the control group ( P<0.001 or P<0.05). During the treatment period, neither group experienced any adverse reactions. Conclusion:The combination of Chinese materia medica soaking therapy and cervical rotation-traction manipulation can significantly improve the clinical symptoms and quality of life of patients with CSR, and its efficacy is superior to the use of cervical rotation-traction manipulation alone.

Objective:To construct a sizeable naive human Fab phage display antibody library to screen high-affinity specific antibodies in vitro. Methods:Total RNA was extracted from peripheral blood mononuclear cells (PBMCs) of 126 healthy individuals, subsequently reverse-transcribed into cDNA, and used as a template. PCR amplification was performed to obtain the V H from IgG, IgM and light chain κ, λ, separately, with the initial PCR products serving as templates for a second round of PCR. Overlap extension PCR was employed to generate fragments of the κ and λ light chains. These fragments were ligated with the phage vector pNC3, which harbors the variable region 1 of the heavy chain, to construct a recombinant phage plasmid. This plasmid was then electroporated into competent Escherichia Coli TG1 cells to establish a naive human Fab phage display antibody library. One hundred clones were randomly selected for identification and sequencing, and antibody gene polymorphisms were analyzed using the IMGT database and MAFFT software. Recombinant α-hemolysin from Staphylococcus aureus was utilized to screen Fab antibody fragments through biopanning of the antibody library, followed by random selection of phage ELISA-identified clones. The positive clones (antigen A450∶blank control A450≥2.1) were sequenced. Results:Two large naive Fab phage display antibody libraries were successfully constructed, in which the capacity of κ and λ chain antibody libraries were 1.25×10 11 and 1.54×10 11, respectively. The titers for two antibody libraries were 6.04×10 13 CFU/ml and 3.50×10 13 CFU/ml. The positive transformation insertion rates for κ and λ chain antibody libraries were 96% (96/100) and 100% (100/100), respectively. Sequence analysis revealed that all antibody sequences were unique. The amino acid sequences in the skeletal region were relatively conserved. In contrast, significant variations in the length of the complementarity determining region (CDR) were found, and the diversity of amino acid sequence of the complementary determining region was high, especially the CDR3. Analysis using the IMGT database indicated that the sequences exhibited a broad distribution across variable-diversity-joining gene families. After six rounds of panning, specific phage antibodies enrichment targeting α-hemolysin were achieved. A total of 142 monoclonal antibodies were sequenced, yielding 8 distinct Fab antibody sequences. Conclusion:This study successfully constructed two naive human Fab phage display antibody libraries with large capacity and good diversity, which can be used for screening human antibodies for serum epidemiology.

Peri-implant keratinized mucosa (PIKM) augmentation refers to surgical procedures aimed at increasing the width of PIKM. Consensus reports emphasize the necessity of maintaining a minimum width of PIKM to ensure long-term peri-implant health. Currently, several surgical techniques have been validated for their effectiveness in increasing PIKM. However, the selection and application of PIKM augmentation methods may present challenges for dental practitioners due to heterogeneity in surgical techniques, variations in clinical scenarios, and anatomical differences. Therefore, clear guidelines and considerations for PIKM augmentation are needed. This expert consensus focuses on the commonly employed surgical techniques for PIKM augmentation and the factors influencing their selection at second-stage surgery. It aims to establish a standardized framework for assessing, planning, and executing PIKM augmentation procedures, with the goal of offering evidence-based guidance to enhance the predictability and success of PIKM augmentation.
Humans ; Consensus ; Dental Implants ; Mouth Mucosa/surgery* ; Keratins

Objective To identify high-risk factors for healthcare-associated infection(HAI)in patients in inten-sive care units(ICUs),and develop a quick response(QR)code-based APP prediction tool.Methods Information of inpatients in general ICUs of three hospitals in Guizhou Province from January to December 2024 were collected.Risk factors were analyzed with a logistic regression model.QR code-based APP was constructed and validated.Results A total of 1 782 patients in general ICUs of three hospitals in Guizhou Province in 2024 were included in the analysis,out of which 410 were HAI cases,and the incidence of HAI was 23.01％.Multivariate logistic regre-ssion analysis results of HAI in ICU inpatients showed that regional gross domestic product(GDP)≥58 685 Yuan,performing pathogen culture during this hospitalization,history of diabetes mellitus,history of cancer,length of hospital stay ≥7 days before infection,and duration of persistent fever＞5 days before infection were independent risk factors for HAI in ICU patients(all P＜0.05).The discrimination of the model(area under the receiver operating characteristic curve[AUC]of 0.841),calibration(Brier score of 0.129),and clinical effectiveness(net benefit of 11.4％when the risk threshold was 5％-74％)all performed well.Conclusion The QR code-based APP prediction tool is of great significance for scientific research transformation and precise HAI control.

Objective:To construct a sizeable naive human Fab phage display antibody library to screen high-affinity specific antibodies in vitro. Methods:Total RNA was extracted from peripheral blood mononuclear cells (PBMCs) of 126 healthy individuals, subsequently reverse-transcribed into cDNA, and used as a template. PCR amplification was performed to obtain the V H from IgG, IgM and light chain κ, λ, separately, with the initial PCR products serving as templates for a second round of PCR. Overlap extension PCR was employed to generate fragments of the κ and λ light chains. These fragments were ligated with the phage vector pNC3, which harbors the variable region 1 of the heavy chain, to construct a recombinant phage plasmid. This plasmid was then electroporated into competent Escherichia Coli TG1 cells to establish a naive human Fab phage display antibody library. One hundred clones were randomly selected for identification and sequencing, and antibody gene polymorphisms were analyzed using the IMGT database and MAFFT software. Recombinant α-hemolysin from Staphylococcus aureus was utilized to screen Fab antibody fragments through biopanning of the antibody library, followed by random selection of phage ELISA-identified clones. The positive clones (antigen A450∶blank control A450≥2.1) were sequenced. Results:Two large naive Fab phage display antibody libraries were successfully constructed, in which the capacity of κ and λ chain antibody libraries were 1.25×10 11 and 1.54×10 11, respectively. The titers for two antibody libraries were 6.04×10 13 CFU/ml and 3.50×10 13 CFU/ml. The positive transformation insertion rates for κ and λ chain antibody libraries were 96% (96/100) and 100% (100/100), respectively. Sequence analysis revealed that all antibody sequences were unique. The amino acid sequences in the skeletal region were relatively conserved. In contrast, significant variations in the length of the complementarity determining region (CDR) were found, and the diversity of amino acid sequence of the complementary determining region was high, especially the CDR3. Analysis using the IMGT database indicated that the sequences exhibited a broad distribution across variable-diversity-joining gene families. After six rounds of panning, specific phage antibodies enrichment targeting α-hemolysin were achieved. A total of 142 monoclonal antibodies were sequenced, yielding 8 distinct Fab antibody sequences. Conclusion:This study successfully constructed two naive human Fab phage display antibody libraries with large capacity and good diversity, which can be used for screening human antibodies for serum epidemiology.

Objective To identify high-risk factors for healthcare-associated infection(HAI)in patients in inten-sive care units(ICUs),and develop a quick response(QR)code-based APP prediction tool.Methods Information of inpatients in general ICUs of three hospitals in Guizhou Province from January to December 2024 were collected.Risk factors were analyzed with a logistic regression model.QR code-based APP was constructed and validated.Results A total of 1 782 patients in general ICUs of three hospitals in Guizhou Province in 2024 were included in the analysis,out of which 410 were HAI cases,and the incidence of HAI was 23.01％.Multivariate logistic regre-ssion analysis results of HAI in ICU inpatients showed that regional gross domestic product(GDP)≥58 685 Yuan,performing pathogen culture during this hospitalization,history of diabetes mellitus,history of cancer,length of hospital stay ≥7 days before infection,and duration of persistent fever＞5 days before infection were independent risk factors for HAI in ICU patients(all P＜0.05).The discrimination of the model(area under the receiver operating characteristic curve[AUC]of 0.841),calibration(Brier score of 0.129),and clinical effectiveness(net benefit of 11.4％when the risk threshold was 5％-74％)all performed well.Conclusion The QR code-based APP prediction tool is of great significance for scientific research transformation and precise HAI control.

Objective To analyze the clinicopathological features,treatment and prognosis of patients with proliferative glomerulonephritis with monoclonal immunoglobulin deposition.Methods The clinical data,renal pathology,treatment and prognosis of patients with PGNMID diagnosed by renal biopsy in Xijing Hospital from January 2018 to January 2024 were retrospectively analyzed and summarized.Results A total of 28 patients were enrolled in this study,with a male to female ratio of 4:3.The clinical manifestations were proteinuria(100%),hematuria(82.1%),renal insufficiency(28.6%),and low complement C3 or C4 emia(32.1%).One patient(3.6%)had serum monoclonal immunoglobulin,and 5 patients(17.9%)had abnormal serum free light chain ratio.The deposition of immunoglobulin in the kidney was IgG3 in 24 cases,IgG1 in 4 cases,and IgG3κwas the most common type(17 cases).Then there are 24 cases(85.7%)of MPGN,3 cases(10.7%)characterized by EPGN,1 case(3.6%)of MGN.Under electron microscope,most of the electron-dense deposits were found in the mesangial area and subendothelium,and a few were accompanied by subepithelial deposits.The follow-up time ranged from 3 to 56 months.Until the last follow-up,a total of 5 patients entered ESRD,of which 2 patients died,1 patient underwent peritoneal dialysis,1 patient underwent hemodialysis,and 1 patient underwent preparation for renal replacement therapy.Follow-up of 1 year,2 years,3 years renal total response rate of 32.1%,57.1%and 64.2%respectively.According to the situation of kidney ease into remission group(n=16)and non-remission group(n=12).The average age of the remission group was 44±17.35 years,including 8 males(50%);The average age of the non-remission group was 59.83±18.09 years,including 8 males(66.7%).The age,nT-proBNP,troponin I and urea nitrogen of the non-remission group were higher than those of the remission group,and the differences were statistically significant(P＜0.05).Among the 5 patients with renal complete remission,2 were treated with BD(bortezomib combined with dexamethasone),1 was treated with Dara,and the remaining 2 were treated with steroids combined with immunosuppressants.Conclusions The clinical manifestations of PGNMID are proteinuria,hematuria and renal insufficiency.Under light microscope,MPGN was the main manifestation,and IgG3κwas the most common subtype.Based on bortezomib treatment can obtain good hematology and kidney remission rate.Dara may be a safe and effective drug for the treatment of PGNMID,the best treatment needs further exploration.

Gongju(Chrysanthemum morifolium) is one of the five major medicinal Chrysanthemum varieties included in the Chinese Pharmacopoeia. In recent years, its cultivation areas have changed significantly, resulting in mixed quality of the medicinal herbs. In this study, Gongju cultivated in Anhui, Yunnan, Chongqing, and other places were selected as research objects. Hyperspectral data were collected in the visible-near-infrared(VNIR) and short-wave infrared(SWIR) bands using different modes, such as corolla facing up(A) and flower base facing up(B). After pre-processing the hyperspectral data using five methods, including multiplicative scatter correction(MSC), Savitzky-Golay smoothing(SG), first derivative(D1), second derivative(D2), and standard normal variate(SNV), partial least squares discriminant analysis(PLSDA), random forest(RF), and support vector machine(SVM) were used to establish origin identification models of Gongju at the two geographical scales of the province and the city-county in Anhui province. The accuracy of the prediction results was used as an evaluation index to select the optimal models, and the classification performance of the models was evaluated by confusion matrix. The results showed that the flower base facing up(B) collection model combined with second derivative pretreatment and RF method was the best model for both geographical scale identification models. The modeling effect of the full-band(VNIR + SWIR) was slightly better than that of the single band, with the accuracy of the prediction set in the province and city-county regions reaching 99.69% and 99.40%, respectively. The competitive adaptive reweighted sampling algorithm(CARS), successive projections algorithm(SPA), and variable iterative space shrinkage approach(VISSA) were further used to screen the feature wavelength modeling. The number of feature wavelengths screened by CARS was fewer, and the prediction set accuracy of the two geographical scales models after optimization could reach 99.56% and 98.65%, which was basically comparable to the full-band model. However, the removal of redundant variables could greatly reduce the complexity of the model. The hyperspectral technology combined with the chemometrics model established in this study can achieve the origin identification of Gongju at different geographical scales, providing a theoretical basis and technical reference for the construction of a rapid detection system for Gongju origin and the development of exclusive miniaturized instrumentation and equipment systems.
Chrysanthemum/growth & development* ; China ; Support Vector Machine ; Geography ; Discriminant Analysis ; Spectroscopy, Near-Infrared/methods* ; Spectrum Analysis/methods* ; Drugs, Chinese Herbal/analysis* ; Least-Squares Analysis

Objective To analyze the clinicopathological features,treatment and prognosis of patients with proliferative glomerulonephritis with monoclonal immunoglobulin deposition.Methods The clinical data,renal pathology,treatment and prognosis of patients with PGNMID diagnosed by renal biopsy in Xijing Hospital from January 2018 to January 2024 were retrospectively analyzed and summarized.Results A total of 28 patients were enrolled in this study,with a male to female ratio of 4:3.The clinical manifestations were proteinuria(100%),hematuria(82.1%),renal insufficiency(28.6%),and low complement C3 or C4 emia(32.1%).One patient(3.6%)had serum monoclonal immunoglobulin,and 5 patients(17.9%)had abnormal serum free light chain ratio.The deposition of immunoglobulin in the kidney was IgG3 in 24 cases,IgG1 in 4 cases,and IgG3κwas the most common type(17 cases).Then there are 24 cases(85.7%)of MPGN,3 cases(10.7%)characterized by EPGN,1 case(3.6%)of MGN.Under electron microscope,most of the electron-dense deposits were found in the mesangial area and subendothelium,and a few were accompanied by subepithelial deposits.The follow-up time ranged from 3 to 56 months.Until the last follow-up,a total of 5 patients entered ESRD,of which 2 patients died,1 patient underwent peritoneal dialysis,1 patient underwent hemodialysis,and 1 patient underwent preparation for renal replacement therapy.Follow-up of 1 year,2 years,3 years renal total response rate of 32.1%,57.1%and 64.2%respectively.According to the situation of kidney ease into remission group(n=16)and non-remission group(n=12).The average age of the remission group was 44±17.35 years,including 8 males(50%);The average age of the non-remission group was 59.83±18.09 years,including 8 males(66.7%).The age,nT-proBNP,troponin I and urea nitrogen of the non-remission group were higher than those of the remission group,and the differences were statistically significant(P＜0.05).Among the 5 patients with renal complete remission,2 were treated with BD(bortezomib combined with dexamethasone),1 was treated with Dara,and the remaining 2 were treated with steroids combined with immunosuppressants.Conclusions The clinical manifestations of PGNMID are proteinuria,hematuria and renal insufficiency.Under light microscope,MPGN was the main manifestation,and IgG3κwas the most common subtype.Based on bortezomib treatment can obtain good hematology and kidney remission rate.Dara may be a safe and effective drug for the treatment of PGNMID,the best treatment needs further exploration.